PMID- 16562097
TI  - Impairment of Temperate Bacteriophage Adsorption by Brief Treatment of
      Escherichia coli with Dilute Solutions of Ethylenediaminetetraacetate.
AB  - Protass, Jay J. (National Institute of Arthritis and Metabolic Diseases,
      Bethesda, Md.), and David Korn. Impairment of temperate bacteriophage adsorption
      by brief treatment of Escherichia coli with dilute solutions of
      ethylenediaminetetraacetate. J. Bacteriol. 91:143-147. 1966.-Cells of Escherichia
      coli K-12 treated for 2 min with 2 x 10(-4)m ethylenediaminetetraacetate (EDTA)
      are unable to adsorb the temperate bacteriophages lambdavir and 434 but show no
      impairment of their ability to adsorb T-even phages or T5. This finding is
      consistent with the hypothesis that there are basic structural differences
      between the cell-wall receptors involved in the adsorption of the temperate and T
      classes of coliphages.

PMID- 16562098
TI  - Presence of the arginine dihydrolase pathway in Mycoplasma.
AB  - Barile, Michael F. (Division of Biologics Standards, National Institutes of
      Health, Bethesda, Md.), Robert T. Schimke, and Donald B. Riggs. Presence of the
      arginine dihydrolase pathway in Mycoplasma. J. Bacteriol. 91:189-192. 1966.-The
      presence of the arginine dihydrolase pathway was examined in 61 Mycoplasma
      strains representing at least 18 Mycoplasma species isolated from nine different
      sources: human, bovine, avian, murine, swine, goat, canine, sewage, and tissue
      cell culture origin. Some species were represented by only one or two strains.
      Different strains of the same species gave the same results. Ten species (56%)
      were positive. Many nonpathogenic Mycoplasma species (M. hominis, type 1 and 2,
      M. fermentans, M. salivarium, and M. gallinarum) were positive, whereas most
      pathogenic species (M. pneumoniae, M. gallisepticum, M. neurolyticum, and M.
      hyorhinis) were negative. The presence of arginine dihydrolase activity among
      Mycoplasma species may prove to be useful for purposes of identification and
      classification.

PMID- 16562099
TI  - Interaction of staphylococcal enterotoxin B with cell cultures of human embryonic
      intestine.
AB  - Schaeffer, W. I. (Massachusetts Institute of Technology, Cambridge), J. Gabliks,
      and R. Calitis. Interaction of staphylococcal enterotoxin B with cell cultures of
      human embryonic intestine. J. Bacteriol. 91:21-26. 1966.-The cytotoxic effect of
      staphylococcal enterotoxin B upon human embryonic intestine cell cultures is
      characterized by retraction of cells from the monolayer. This is followed by
      clumping of the retracted cells to form clear areas in the monolayer and finally
      by sloughing of the clumps from the glass surface. The 50% effective dose of the
      toxin, determined by protein analysis of the cultures used in titration studies,
      was found to be between 40 and 60 mug/ml. The cytotoxic property of the
      enterotoxin was completely neutralized by 3.9 x 10(-5) ml of specific antitoxin
      per mug of toxin. The cytotoxicity was found to be slightly enhanced by 2.2 g of
      bicarbonate per liter of Eagle's basal medium (Earle's salt solution level), the
      absence of serum, the absence of penicillin and streptomycin, and the presence of
      2.8 mmoles of calcium in the medium. The cytotoxicity was profoundly influenced
      by the age of the culture. No cytotoxicity was evident until after 2 days of
      growth had taken place, when the cell number was approximately 4.0 x 10(5) cells
      per culture.

PMID- 16562100
TI  - Immunofluorescence of green monkey kidney cells infected with adenovirus 12 and
      with adenovirus 12 plus simian virus 40.
AB  - Malmgren, Richard A. (National Cancer Institute; Bethesda, Md.), Alan S. Rabson,
      Paula G. Carney, and Frances J. Paul. Immunofluorescence of green monkey kidney
      cells infected with adenovirus 12 and with adenovirus 12 plus simian virus 40. J.
      Bacteriol. 91:262-265. 1966.-Immunofluorescence studies of the viral antigens and
      tumor (T) antigens of adenovirus 12 and simian virus 40 (SV40) in green monkey
      kidney (GMK) cells infected with adenovirus 12 alone or in combination with the
      SV40 virus showed that the adenovirus 12 viral antigen was produced in detectable
      amounts only in the cells infected with both viruses. The adenovirus 12 T
      antigen, on the other hand, was formed in the GMK cells infected with the
      adenovirus 12 only. This antigen was formed as early as 18 hr after viral
      infection, and persisted for at least 48 hr after virus infection. There was a
      correlation between the appearance of the immunofluorescent T antigen in the
      nucleus and the electron microscope appearance of "nuclear stippling," which
      developed in the nuclei of GMK cells after infection with adenovirus 12 only, as
      well as after infection with both viruses.

PMID- 16562101
TI  - Variation in Lipid Content of Strains of Histoplasma capsulatum Exhibiting
      Different Virulence Properties for Mice.
AB  - Nielsen, H. S., Jr. (Duke University Medical Center, Durham, N.C.). Variation in
      lipid content of strains of Histoplasma capsulatum exhibiting different virulence
      properties for mice. J. Bacteriol. 91:273-277. 1966.-Lipid content and virulence
      were studied in six isolates of Histoplasma capsulatum in an attempt to determine
      whether or not the two factors could be correlated in this fungus. Virulence was
      evaluated by injecting dba line 1 male mice intracerebrally with 2.8 x 10(4)
      infective yeast-phase units and recording organ involvement and spontaneous
      deaths occurring in a 20-day period. Yeast cells were extracted with mixtures of
      ethyl alcohol-diethyl ether (3:1, v/v), and the total extractable lipid, as
      determined by solubility in petroleum ether, was separated into acetone-soluble
      and phospholipid fractions by acetone precipitation. Neutral lipids were measured
      directly by weighing, whereas total phospholipids were calculated after the
      colorimetric determination of phosphorus. The mixed phosphatides of two isolates,
      differing in virulence, were separated into five fractions by use of a column of
      silicic acid and Hyflo Super-Cel. In the six isolates studied, neither total
      extractable lipid, acetone-soluble lipid, nor phospholipid showed a quantitative
      correlation with virulence. Phosphatidylserine, cephalin, phosphoinositides, and
      sphingolipids were present in essentially the same amounts in the two strains
      investigated; however, a lecithin fraction was absent in the less virulent form.
      These data suggest that the quantity of phosphatidylcholine demonstrated for a
      given isolate of H. capsulatum may provide some insight as to its virulence,
      although such a relationship is lacking for total lipid, the acetone-soluble
      fraction, and the combined phospholipids of yeast-phase growth.

PMID- 16562102
TI  - Intracellular Production of Brucella L Forms I. Recovery of L Forms from Tissue
      Culture Cells Infected with Brucella abortus.
AB  - Hatten, Betty A. (The University of Texas Southwestern Medical School, Dallas),
      and S. Edward Sulkin. Intracellular production of Brucella L forms. I. Recovery
      of L forms from tissue culture cells infected with Brucella abortus. J.
      Bacteriol. 91:285-296. 1966.-Infectivity of virulent Brucella abortus strain 3183
      was less for hamster macrophages after a 2-hr adsorption period than for an
      attenuated strain (S19) and its tissue culture variant (30). Both strains S19 and
      30 were very toxic for the cells, but 3183 was not toxic. Two types of L forms
      were recovered from a large percentage of hamster kidney cell cultures when
      disintegration of infected cells was accelerated by tissue culture medium of high
      pH. One type grew in finely granular microcolonies, was isolated from cells
      infected for short periods of time, and often reverted to the bacterial form. The
      other type occurred in small irregularly shaped forms which later developed into
      round bodies. Both stained specifically with fluorescein-conjugated B. abortus
      antiserum. Semisolid media containing 0.7% agar provided optimal subsurface L
      form growth. L forms also grew well in Thioglycollate Medium but grew poorly in
      other liquid media. Surface L-form growth was supported by several agar media,
      but CO(2) was required for optimal growth. Monolayers infected with strain 3183
      and examined immediately after adsorption contained occasional small, round
      bodies. Bizarre forms increased in number with time and, after 24 to 72 hr, large
      pink-staining inclusions were often present which persisted for several days.
      Also appearing at about the same time were smaller, dark-staining forms which
      were first seen in clusters but later dispersed and finally occurred in chainlike
      configurations. Direct fluorescent-antibody stains of infected cells established
      that the intracellular forms were related to the infecting strain of B. abortus.

PMID- 16562103
TI  - Photosynthetic Apparatus in the Green Bacterium Chloropseudomonas ethylicum.
AB  - Holt, Stanley C. (Dartmouth Medical School, Hanover, N.H.), S. F. Conti, and R.
      C. Fuller. Photosynthetic apparatus in the green bacterium Chloro-pseudomonas
      ethylicum. J. Bacteriol. 91:311-323. 1966.-When cells of Chloro-pseudomonas
      ethylicum were broken by ballistic disruption and examined by electron
      microscopy, vesicles 1,300 to 1,500 A long and 300 to 500 A wide were found to
      rim the periphery of the cell. Examination of these vesicles obtained by
      disruption with a French pressure cell and purified by density gradient
      centrifugation revealed inter-connections between the vesicles. During sonic and
      Mickle disruption of the cells, chlorophyll was released at a lower rate than
      soluble cytoplasmic components, but faster than the membrane-bound enzyme
      succinic dehydrogenase. Unlike the situation that exists in the purple
      photosynthetic bacteria, it appears that the chlorophyll in the green bacteria is
      contained as part of a structure which may be differentiated both structurally
      and functionally from the bacterial cytoplasmic membrane.

PMID- 16562104
TI  - Cell wall lipopolysaccharides from xanthomonas species.
AB  - Volk, Wesley A. (University of Virginia, Charlottesville). Cell wall
      lipopolysaccharides from Xanthomonas species. J. Bacteriol. 91:39-42. 1966.-The
      lipopolysaccharides from 20 species of Xanthomonas were extracted and purified.
      Biological studies suggest that these lipopolysaccharides are analogous to the
      endotoxins extracted from enteric organisms, as judged by their mouse lethality
      and their ability to provoke the local Shwartzman reaction in rabbits. Studies on
      the composition of the polysaccharides revealed that all contained uronic acid,
      glucose, mannose, and a compound apparently identical to the 2-keto-3
      deoxyoctonate previously described in enteric organisms. The polysaccharide also
      contains organic phosphate, and additional carbohydrates such as rhamnose,
      xylose, fucose, and galactose are found in some, but not all, species. In
      contrast to the composition of the enteric lipopolysaccharides, heptose was not
      found in any of the lipopolysaccharides of the Xanthomonas species studied.

PMID- 16562105
TI  - Genetic Recombination in Crosses Between Streptomyces aureofaciens and
      Streptomyces rimosus.
AB  - Polsinelli, M. (University of Pavia, Pavia, Italy), and Maria Beretta. Genetic
      recombination in crosses between Streptomyces aureofaciens and Streptomyces
      rimosus. J. Bacteriol. 91:63-68. 1966.-Biochemical mutants were obtained from
      Streptomyces rimosus and S. aureofaciens by ultraviolet irradiation. Crosses were
      performed between auxotrophic strains of S. rimosus and S. aureofaciens with
      positive results. Data are reported which indicate that the interaction observed
      in some crosses is due to gene recombination.

PMID- 16562106
TI  - Editorial.

PMID- 16562107
TI  - Mechanism of Action of Nalidixic Acid on Escherichia coli V. Possible Mutagenic
      Effect.
AB  - Cook, Thomas M., (Sterling-Winthrop Research Institute, Rensselaer, N.Y.),
      William A. Goss, and William H. Deitz. Mechanism of action of nalidixic acid on
      Escherichia coli. V. Possible mutagenic effect. J. Bacteriol. 91:780-783. 1966.
      With a streptomycin-dependent organism, Escherichia coli ATCC 11143, it has been
      shown that exposure to nalidixic acid, under conditions permitting some
      bactericidal action, results in an increased number of streptomycin-independent
      bacteria among the survivors. This effect is evident only with proliferating
      cultures, and is related to the concentration of nalidixic acid and the duration
      of exposure.

PMID- 16562108
TI  - Isolation of a Soluble Resistance-Enhancing Factor from Mycobacterium phlei.
AB  - Fox, Alfred E. (Warner-Lambert Research Institute, Morris Plains, N.J.), Joachim
      Anschel, George L. Evans, Raam R. Mohan, and Benjamin S. Schwartz. Isolation of a
      soluble resistance-enhancing factor from Mycobacterium phlei. J. Bacteriol.
      92:285-290. 1966.-Extraction of a crude cell wall preparation from Mycobacterium
      phlei with 20% urea yielded a fraction which induced a state of enhanced
      resistance to microbial challenge. The resulting soluble extract, after removal
      of the urea, represented a 15% yield of solids with the separation of the
      biologically active component(s) and elimination of toxicity. Single oral or
      subcutaneous submicrogram doses of this material induced a prolonged state of
      increased resistance to subsequent challenge with Salmonella enteritidis in mice.
      This effect appeared as early as 2 hr after oral administration and persisted for
      at least 30 days. Protection against experimental infection with Staphylococcus
      aureus was also demonstrated. Resistance to viral challenge with influenza type A
      was observed after intranasal administration of the M. phlei extract to mice. The
      isolated material was found to contain carbohydrate, protein, nucleic acids, and
      lipids. The lipids represented 60% of the total solids, and were all short-chain
      fatty acids. No toxic effects, including pyrogenicity, could be demonstrated
      after oral or parenteral administration of this preparation.

PMID- 16562109
TI  - Death of Bacillus subtilis Auxotrophs Due to Deprivation of Thymine, Tryptophan,
      or Uracil.
AB  - Pritikin, William B. (University of California, Los Angeles), and W. R. Romig.
      Death of Bacillus subtilis auxotrophs due to deprivation of thymine, tryptophan,
      or uracil, J. Bacteriol. 92:291-296. 1966.-Auxotrophic mutants of Bacillus
      subtilis 168 that require either tryptophan, uracil, or thymine died rapidly when
      deprived of any of these compounds. Phage PBS1 was produced by infected B.
      subtilis 168 (thy try-2) deprived of thymine. Phage PBS1 was not produced by
      infected B. subtilis 168 (try-2) deprived of tryptophan or infected B. subtilis
      168-15 (try-2 ura) deprived of uracil. B. subtilis 168 thy try-2 and 168-15 could
      be transduced by phage PBS1 after prolonged deprivation of tryptophan or uracil,
      respectively. When B. subtilis 168-15 was transduced to uracil independence by
      phage PBS1, the uracil-independent transductants became immune to uracil-less
      death within 10 min of exposure to phage, and began to multiply within 2 hr after
      exposure to phage at an incubation temperature of 46 C.

PMID- 16562110
TI  - Factors Affecting the Survival of Auxotrophs and Prototrophs of Saccharomyces
      cerevisiae in Mixed Populations.
AB  - Moat, Albert G. (Hahnemann Medical College, Philadelphia, Pa.), Isabel J. Barnes,
      and Eleanor H. McCurley. Factors affecting the survival of auxotrophs and
      prototrophs of Saccharomyces cerevisiae in mixed populations. J. Bacteriol.
      92:297-301. 1966.-The conditions under which the number of yeast prototrophs, as
      well as respiration-deficient mutants, could be materially decreased, while
      allowing the survival of auxotrophic mutants in recoverable numbers, have been
      investigated in detail. Neither the use of carbohydrates other than glucose to
      prevent development of respiration-deficient mutants, nor treatment with
      acriflavine to render all surviving wild types respiration-deficient, provided a
      selective advantage for the auxotrophs. Increased concentrations of the
      antifungal agents amphotericin B or endomycin, while reducing the number of
      respiration-deficient mutants, did not significantly increase the final mutant
      wild type ratio. A more soluble form of amphotericin B (Fungizone), when used
      under carefully defined physiological conditions, produced a significant
      reduction in the number of surviving prototrophs relative to the surviving
      auxotrophs, without development of respiration-deficient mutants.

PMID- 16562111
TI  - Genetic differentiation by nucleic Acid homology I. Relationships among
      Mycoplasma species of man.
AB  - Reich, Paul R. (National Institutes of Health, Bethesda, Md.), Norman L.
      Somerson, Carol J. Hybner, Robert M. Chanock, and Sherman M. Weissman. Genetic
      differentiation by nucleic acid homology. I. Relationships among Mycoplasma
      species of man. J. Bacteriol. 92:302-310. 1966.-Genetic relatedness among human
      mycoplasmas was evaluated by measuring the amount of nucleic acid hybrid retained
      on a membrane filter. Hybrids were formed from deoxyribonucleic acid (DNA) and
      ribonucleic acid (RNA) derived from representative strains of seven serologically
      distinct human Mycoplasma species. The results indicate that serologically
      distinct human Mycoplasma species can also be distinguished by the homology
      techniques. Low-level cross-reactivity was observed among nucleic acids derived
      from the seven species. Genetic heterogeneity was demonstrated among three
      strains of M. salivarium and between two strains of M. orale type 2. In contrast,
      comparison of three strains and three passage levels of M. pneumoniae revealed
      them to be indistinguishable. M. pneumoniae appears to be the most distinct of
      all human mycoplasmas, as shown by both homology and the high buoyant density
      value of its DNA. Nucleic acids from mycoplasmas which had identical buoyant
      densities were in some cases differentiable. Mycoplasmas with different DNA
      buoyant densities were invariably distinguishable by the homology technique.

PMID- 16562112
TI  - Genetic Differentiation by Nucleic Acid Homology II. Genotypic Variations Within
      Two Mycoplasma Species.
AB  - Somerson, Norman L. (National Institutes of Health, Bethesda, Md.), Paul R.
      Reich, Barbara E. Walls, Robert M. Chanock, and Sherman M. Weissman. Genetic
      differentiation by nucleic acid homology. II. Genotypic variations within two
      Mycoplasma species. J. Bacteriol. 92:311-317. 1966.-A deoxyribonucleic
      ribonucleic acid (DNA-RNA) homology technique was used to determine genetic
      relatedness among the nucleic acids of eight mycoplasmas which were serologically
      classified as Mycoplasma hominis type 1. The DNA preparations from these
      organisms were each found to be distinct. No subgrouping of the M. hominis type 1
      strains could be demonstrated. In contrast, when the nucleic acids from six
      serologically related mycoplasmas which were isolated from tissue cultures were
      studied, the DNA from these species could not be distinguished. The DNA buoyant
      densities of the tissue culture isolates were similar. These isolates were
      closely related genetically to a porcine mycoplasma, M. hyorhinis.

PMID- 16562113
TI  - Delayed lactose fermentation by enterobacteriaceae.
AB  - Goodman, R. E. (University of California, Los Angeles), and M. J. Pickett.
      Delayed lactose fermentation by Enterobacteriaceae. J. Bacteriol. 92:318-327.
      1966.-When 171 Citrobacter freundii strains and 14 Paracolobactrum arizonae
      strains examined, 51 of the C. freundii strains and 13 of the P. arizonae strains
      were found to be delayed or negative lactose fermenters. Of the slow fermenters,
      65% yielded rapidly fermenting mutants in cultures undergoing delayed
      fermentation. Lactose fermentation could generally be hastened by increasing
      lactose concentrations. Many organisms which fermented lactose slowly grew
      readily on a medium containing lactose as the sole carbon source. Regardless of
      their ability to ferment lactose, all strains of C. freundii and P. arizonae
      investigated could be shown to possess beta-galactosidase. Delayed fermenters
      failed to take up lactose from the culture medium, whereas prompt fermenters did
      so readily. The beta-galactosidases of 12 strains of enteric bacteria were
      studied in crude cell extracts with respect to specific activity, stability, and
      activity at varying substrate (o-nitrophenyl-beta-d-galactopyranoside)
      concentrations, at varying pH, and in the presence of sodium, potassium, and
      magnesium. The widely varying specific activities and the approximate similarity
      of the Michaelis constants (about 2 x 10(-4)m) suggested that the strains
      investigated produced differing amounts of beta-galactosidase. Moreover,
      qualitative differences in the enzymes provided evidence that these strains
      synthesized different molecular forms of beta-galactosidase. The results
      suggested that organisms which ferment lactose only after a prolonged delay do so
      because they possess multiple defects in their lactose-metabolizing machinery.

PMID- 16562114
TI  - Utilization of d-Methionine by Escherichia coli.
AB  - Cooper, Stephen (University Institute of Microbiology, Copenhagen, Denmark).
      Utilization of d-methionine by Escherichia coli. J. Bacteriol. 92:328-332. 1966.
      Methionine-requiring strains of Escherichia coli grow on d-methionine. Mutants
      can be isolated which cannot grow on d-methionine. The d-methionine nonutilizing
      mutation is independent of the methionine requirement, and maps near the lac
      region of the E. coli genome. Growth of methionine-requiring strains on d
      methionine is dependent upon aerobic conditions. Cells grown on d-methionine have
      a sixfold greater ability to incorporate d-methionine into protein than cells
      grown on l-methionine. The incorporation of d-methionine is inhibited by l
      methionine.

PMID- 16562115
TI  - Synthesis of Pyridoxine by a Pyridoxal Auxotroph of Escherichia coli.
AB  - Dempsey, Walter B. (University of Florida, Gainesville). Synthesis of pyridoxine
      by a pyridoxal auxotroph of Escherichia coli. J. Bacteriol. 92:333-337. 1966.-A
      pyridoxal auxotroph of Escherichia coli B produced pyridoxol and pyridoxol 5'
      phosphate during starvation for pyridoxal. The identification of these compounds
      was made both by bioassay and by ion-exchange chromatography. Pyridoxol 5'
      phosphate oxidase activity was absent in extracts of the auxotroph. The rate of
      synthesis of total pyridoxine by a pyridoxal-starved culture of this auxotroph
      was 6.0 x 10(-6) moles per mg per hr. Cellular content of pyridoxine was constant
      at 4.0 x 10(-10) moles/mg.

PMID- 16562116
TI  - Occurrence and Distribution of Proteinase of Streptococcus faecalis var.
      liquefaciens.
AB  - Shugart, Lee R. (University of Tennessee, Knoxville), and Raymond W. Beck.
      Occurrence and distribution of proteinase of Streptococcus faecalis var.
      liquefaciens. J. Bacteriol. 92:338-341. 1966.-The proteolytic enzyme produced by
      Streptococcus faecalis var. liquefaciens (ATCC 13398) was shown to be an
      exoenzyme. The production of the proteinase was followed in growing cultures, and
      its distribution was compared with that of the intracellular enzymes reduced
      nicotinamide adenine dinucleotide (NADH(2)) peroxidase and lactate dehydrogenase.
      The proteinase appeared in the culture medium prior to the stationary phase of
      growth, whereas the other enzymes could be found only in whole cells.
      Fractionation of whole cells by sonic treatment and by treatment with lysozyme
      showed the proteinase to be associated primarily with the cell wall and cell
      membrane, and NADH(2) peroxidase to be associated only with the cytoplasmic
      fractions.

PMID- 16562117
TI  - Isolation and Identification of Canthaxanthin from Micrococcus roseus.
AB  - Cooney, J. J. (University of Dayton, Dayton, Ohio), H. W. Marks, Jr., and Anne M.
      Smith. Isolation and identification of canthaxanthin from Micrococcus roseus. J.
      Bacteriol. 92:342-345. 1966.-The principal colored carotenoid of Micrococcus
      roseus was purified by solvent partitioning followed by column and thin-layer
      chromatography. Absorption spectra, partition coefficients, and infrared spectra
      suggested that the pigment was a diketo derivative of beta-carotene. The pigment
      was subjected to reduction, and the reduced pigment was subsequently dehydrated.
      Spectral data and partition coefficients of these derivatives indicated that the
      original pigment was canthaxanthin (4',4'-diketo-beta-carotene). The pigment was
      an all-trans isomer; it does not exist as an ester in M. roseus. Canthaxanthin
      has not previously been identified as a bacterial pigment.

PMID- 16562118
TI  - Effects of 5-Fluorouracil and 5-Fluorodeoxyuridine on Growth and Tumor-Inducing
      Ability of Agrobacterium tumefaciens.
AB  - Beardsley, Robert E. (Manhattan College, Bronx, N.Y.), and Jacques Lipetz Effects
      of 5-fluorouracil and 5-fluorodeoxyuridine on growth and tumor-inducing ability
      of Agrobacterium tumefaciens. J. Bacteriol. 92:346-348. 1966.-Agrobacterium
      tumefaciens B6, grown in the presence of 5-fluorouracil or 5-fluodeoxyuridine,
      exhibited a prolonged lag phase. The tumor-inducing ability of bacteria grown in
      the presence of these compounds was decreased even after exposures as short as 40
      min. A positive correlation was found between the growth-inhibitory effects of
      these compounds and their effects on the tumor-inducing ability of the bacteria.

PMID- 16562119
TI  - Leukocytic response in monkeys challenged with staphylococcal enterotoxin.
AB  - Sugiyama, H. (University of Chicago, Chicago, Ill.), and E. M. McKissic, Jr.
      Leukocytic response in monkeys challenged with staphylococcal enterotoxin. J.
      Bacteriol. 92:349-352. 1966-The feeding of staphylococcal enterotoxin to monkeys
      elicited a leukocytosis which was evident within 0.5 hr of challenge. The peak
      neutrophilic leukocytosis was reached in 3 hr, and then subsided so that
      leukocyte counts were normal within 28 hr. Each of the three serological types of
      enterotoxin tested induced the same effects. Intravenous injection of enterotoxin
      slightly above the emetic ed(50) level produced an initial leukopenia followed by
      a neutrophilic leukocytosis which was maximal 9 or more hr postinjection. With
      smaller intravenous challenges, some animals responded with a leukopenia followed
      by a leukocytosis, some with only a leukocytosis, and others with no significant
      change in total leukocyte counts. The reversal of normal lymphocyte-to
      neutrophile ratio toward a neutrophile-predominant white blood cell population
      occurred in all animals.

PMID- 16562120
TI  - Effects of Dimethylsulfoxide on the Lactose Operon in Escherichia coli.
AB  - Fowler, Audree V. (University of California, Los Angeles), and Irving Zabin.
      Effects of dimethylsulfoxide on the lactose operon in Escherichia coli. J.
      Bacteriol. 92:353-357. 1966.-Dimethylsulfoxide (DMSO) at a concentration of 5%
      (v/v) in the culture medium inhibits the growth of Escherichia coli to only a
      slight extent, and does not affect the differential rate of synthesis of beta
      galactosidase. Resting cells remain viable after shaking in the presence of 20%
      DMSO for 3 hr at 37 C. Both beta-galactosidase and thiogalactoside transacetylase
      retain almost all activity after incubation in even higher concentrations of the
      solvent for many hours. DMSO decreases the permeability barrier. The rate of
      hydrolysis of o-nitrophenyl-beta-d-galactoside (ONPG) in whole cells containing
      beta-galactosidase but lacking permease is increased in cells treated with 5%
      DMSO. Several permeaseless strains preinduced for beta-galactosidase will grow on
      lactose in the presence, but not in the absence, of 5% DMSO. When permeaseless
      strains are grown on tetrazolium-lactose-agar, the presence of 5% DMSO causes a
      definite but not marked shift toward the lactose-positive character.

PMID- 16562121
TI  - Mechanisms of antibiotic resistance determined by resistance-transfer factors.
AB  - Unowsky, Joel (Northwestern University Medical School, Chicago, Ill.), and Martin
      Rachmeler. Mechanisms of antibiotic resistance determined by resistance-transfer
      factors. J. Bacteriol. 92:358-365. 1966.-This study was concerned with the
      mechanism of expression of drug resistance carried by resistance-transfer (R)
      factors of two types: fi(-) (negative fertility inhibition) and fi(+) (positive
      fertility inhibition). The levels of drug resistance determined by R factors used
      in this study were similar to those reported by other investigators. A new
      finding was that Escherichia coli carrying the fi(-) episome was resistant to 150
      to 200 mug/ml of streptomycin. The growth kinetics of R factor-containing cells
      were similar in the presence or absence of streptomycin, chloramphenicol, and
      tetracycline, but a period of adaptation was necessary before cells began
      exponential growth in the presence of tetracycline. By use of radioactive
      antibiotics, it was shown that cells containing the fi(-) episome were
      impermeable to tetracycline and streptomycin, whereas cells containing the fi(+)
      episome were impermeable only to chloramphenicol. Cell-free extracts from fi(+)
      and fi(-) cells were sensitive to the antibiotics tested in the polyuridylic acid
      stimulated incorporation of phenylalanine into protein.

PMID- 16562122
TI  - Effect of Bromouracil-containing Deoxyribonucleic Acid on Bacillus subtilis.
AB  - Gimlin, Dixie M. (Oklahoma State University, Stillwater), Sue D. Hardman, Betty
      N. Kelley, Grace C. Butler, and Franklin R. Leach. Effect of bromouracil
      containing deoxyribonucleic acid on Bacillus subtilis. J. Bacteriol. 92:366-374.
      1966.-Replacement of one-half of the thymine with bromouracil in Bacillus
      subtilis transforming deoxyribonucleic acid (DNA) resulted in a slight decrease
      in transforming activity, but, when used at high concentrations, this DNA
      preparation inhibited cell growth. Acid-hydrolyzed DNA, or addition of equivalent
      concentrations of the free base bromouracil in a transforming mixture, was
      without effect on cell growth. Treatment of the DNA preparation with
      deoxyribonuclease completely destroyed transforming activity and killing effect,
      whereas treatments with ribonuclease and trypsin were without effect on either
      transformation or killing activity. Growth of competent B. subtilis cells in test
      tubes was inhibited by high concentrations of both normal and bromouracil
      containing DNA, with the bromouracil-containing DNA being significantly more
      inhibitory. This type of inhibition was also reflected in the time of division of
      the cells. The inhibitory effect was not due to viscosity, or to mutagenicity.
      The time course of killing paralleled transformation, and competency was
      required. These results can be interpreted as being due to uptake of homologous
      but imperfect DNA (containing bromouracil instead of thymine) by means of the
      systems involved in transformation, followed by either integration (resulting in
      lethal transformation, activation of a defective, nonlytic but lethal prophage)
      or interference with the recombination mechanism.

PMID- 16562123
TI  - Feedback regulation of arginine biosynthesis in blue-green algae and
      photosynthetic bacteria.
AB  - Hoare, D. S. (The University of Texas, Austin), and S. L. Hoare. Feedback
      regulation of arginine biosynthesis in blue-green algae and photosynthetic
      bacteria. J. Bacteriol. 92:375-379. 1966.-A number of blue-green algae and
      photosynthetic bacteria synthesize arginine from glutamate via acetylated
      intermediates. Cell-free extracts of these photosynthetic microorganisms contain
      an N-acetyl glutamate phosphokinase, which is specifically inhibited by arginine.
      They also contain a transacetylase which forms ornithine from alphaN-acetyl
      ornithine and glutamate. The transacetylase appears to be specific for l
      glutamate. Arginine synthesis and its regulation by feedback inhibition in
      photosynthetic microorganisms differ from that in Escherichia coli and other
      Enterobacteriaceae.

PMID- 16562124
TI  - Role of Multivalent Cations in the Organization, Structure, and Assembly of the
      Cell Wall of Pseudomonas aeruginosa.
AB  - Asbell, Mary A. (University of Georgia, Athens), and R. G. Eagon. Role of
      multivalent cations in the organization, structure, and assembly of the cell wall
      of Pseudomonas aeruginosa. J. Bacteriol. 92:380-387. 1966. -Incubation of
      Pseudomonas aeruginosa with ethylenediaminetetraacetate induced the formation of
      osmotically fragile rods termed osmoplasts. These could be restored to
      osmotically stable forms by multivalent cations. Only those cells restored by
      divalent cations normally found in the cell wall were capable of multiplication.
      The respiration of restored cells, however, was unimpaired, irrespective of
      whether they were capable of multiplication. Moreover, the permeability
      characteristics of osmoplasts and restored cells were unimpaired. When
      multivalent cations were chelated from the cell wall and replaced by sodium, a
      weakened cell wall and an osmotically fragile cell resulted. This was apparently
      caused by the absence of cross-linkages in the cell wall via multivalent cations.
      Tris(hydroxymethyl)aminomethane buffer compounded the lethal effects of
      ethylenediaminetetraacetate. The lipopolysaccharide component was inferred to be
      the site of attack by ethylenediaminetetraacetate. A mechanism for the synthesis
      of the lipopolysaccharide sacculus was proposed whereby negatively charged
      subunits are "trapped" by forming ionic and coordinate bonds intermediated by
      multivalent cations.

PMID- 16562125
TI  - Adsorption Specificity of Bacteriophage PBS1.
AB  - Frankel, Ruth W. (University of Oregon Medical School, Portland), and Terence M.
      Joys. Adsorption specificity of bacteriophage PBS1. J. Bacteriol. 92:388-389.
      1966.-By use of newly isolated nonflagellate mutants, the location of the
      receptor site for phage PBS1 is confirmed as being on the flagella of Bacillus
      subtilis. Tests with partially purified flagella isolated from a culture of
      susceptible organisms, and with a strain of B. subtilis possessing nonfunctional
      flagella, show that phage PBS1 has an adsorption specificity for active flagella.

PMID- 16562126
TI  - Immunological tolerance to microbial antigens I. Absence of specific antibody
      containing cells in lymphoid tissue of mice injected at birth with Shigella
      soluble antigen.
AB  - Friedman, Herman (Albert Einstein Medical Center, Philadelphia, Pa.).
      Immunological tolerance to microbial antigens. I. Absence of specific antibody
      containing cells in lymphoid tissue of mice injected at birth with Shigella
      soluble antigen. J. Bacteriol. 92:390-397. 1966.-Injection of a relatively large
      concentration of Shigella soluble antigen (SSA) into newborn mice results in
      specific immunological tolerance (paralysis) characterized by inability of the
      animals to form normal levels of anti-Shigella agglutinins upon subsequent
      challenge immunization with Shigella. Spleen and lymph nodes from Shigella
      tolerant mice, as well as from normal and control immunized mice, were examined
      by the indirect immunofluorescence technique for evidence of cells containing
      anti-Shigella antibody. It was found that mice sacrificed at periodic intervals
      after neonatal administration of the tolerance-inducing inoculum of antigen and
      prior to and following challenge injection with a potential immunizing dose of
      SSA had only occasional specific fluorescing cells in spleens and lymph nodes.
      Tolerant mice also failed to develop significant levels of specific serum
      agglutinins after SSA challenge injection. In contrast, normal adult mice had a
      rapid appearance of numerous specific fluorescing cells in their spleens and
      lymph nodes, as well as a marked agglutinin response, after SSA immunization.
      Shigella-tolerant and normal control mice responded equally well with anti
      Salmonella agglutinin formation and specific antibody-containing lymphoid cells
      after immunization with Salmonella antigen.

PMID- 16562127
TI  - Retention of episomes during protoplasting and during propagation in the L state.
AB  - Kawakami, Masaya (Georgetown University, Washington, D.C.), and Otto E. Landman.
      Retention of episomes during protoplasting and during propagation in the L state.
      J. Bacteriol. 92:398-404. 1966.-In earlier work, it was observed that the
      mesosomes of Bacillus magaterium and B. subtilis are expelled from the cell
      interior during protoplasting and that mesosome fragments are released into the
      supernatant fluid as the cell wall disintegrates. Since the resultant protoplasts
      remain intact and capable of reproduction, the expelled contents of the mesosome
      "bag" are presumably external to the protoplast membrane and nonessential to
      survival. Accordingly, if episomes (plasmids) were localized in the extramembrane
      mesosome "bag," it would be predicted that protoplasting would cure cells of
      their episomes. This prediction was tested in three different systems: B.
      subtilis W23 carrying phage SP-10, B. megaterium 216 carrying megacinogenic
      factors A and C, and B. megaterium C4M(-) carrying megacinogenic factor C. No
      curing due to protoplasting was observed. Even during propagation in the L form,
      when septation is not functioning and the distribution of deoxyribonucleic acid
      to daughter cells is severely disrupted, curing was not observed in any of the
      above systems nor in Salmonella L forms carrying F(0)lac. It is concluded that
      episomes are located at a position on the interior side of the cell membrane and
      that their distribution to daughter cells is coordinated with that of the
      chromosome.

PMID- 16562128
TI  - Properties of Nicotinamide Adenine Dinucleotide Phosphate-Dependent Formate
      Dehydrogenase from Clostridium thermoaceticum.
AB  - Li, Lan-Fun (Western Reserve University School of Medicine, Cleveland, Ohio),
      Lars Ljungdahl, and Harland G. Wood. Properties of nicotinamide adenine
      dinucleotide phosphate-dependent formate dehydrogenase from Clostridium
      thermoaceticum. J. Bacteriol. 92: 405-412. 1966.-A nicotinamide adenine
      dinucleotide phosphate (NADP)-dependent formate dehydrogenase has been isolated
      from C. thermoaceticum. The enzyme is very sensitive to oxygen and requires
      sulfhydryl compounds for activity. The apparent K(m) at 50 C and pH 7.0 for NADP
      is 5.9 x 10(-5)m and for formate, 2.2 x 10(-4)m. The enzyme is most active at
      about 60 C and at pH values between 7.0 and 9.0. The enzyme catalyzes an exchange
      between C(14)O(2) and formate, which requires NADP, but net synthesis of formate
      from CO(2) and reduced nicotinamide adenine dinucleotide phosphate could not be
      demonstrated. The reaction does not involve ferredoxin.

PMID- 16562129
TI  - Peroxidatic activity of mycobacteria and relation to catalase.
AB  - Winder, Frank G. (Trinity College, Dublin, Ireland). Peroxidatic activity of
      mycobacteria and relation to catalase. J. Bacteriol. 92:413-417. 1966.-Catalase
      from Mycobacterium smegmatis was purified about 50-fold. All fractions showed a
      ratio of peroxidatic activity to catalatic activity approximately the same as
      that of the crude extract, a ratio only about four times that given by catalase
      from Micrococcus lysodeikticus. This and other evidence strongly suggest that the
      peroxidatic activity of M. smegmatis is due to its catalase. Less complete
      evidence suggests that this is true in the case of Mycobacterium tuberculosis
      also. It is suggested that in the context of the mycobacteria the term
      "peroxidatic activity" should replace the term "peroxidase" unless evidence is
      found that a true peroxidase exists in these organisms.

PMID- 16562130
TI  - Thermolability of Malic Dehydrogenase from the Obligate Psychrophile Vibrio
      marinus.
AB  - Langridge, Patricia (Oregon State University, Corvallis), and Richard Y. Morita.
      Thermolability of malic dehydrogenase from the obligate psychrophile Vibrio
      marinus. J. Bacteriol. 92:418-423. 1966.-The thermolability of malic
      dehydrogenase in whole cells of Vibrio marinus MP-1 grown at 15 C was compared
      with that of cell-free extracts and partially purified fractions. The
      intracellular enzyme was found to be stable between 0 C, and the organism's
      optimal growth temperature, 15 C. In cell-free extracts, considerable lability
      was noted even at 0 C, and this lability did not increase further until the
      enzyme was exposed to temperatures above the organism's maximal growth
      temperature (20 C). Twenty-fold purified enzyme was stable between 15 and 20 C,
      but both above and below this there was considerable inactivation. A 5-min
      exposure of both cold- and heat-inactivated enzyme to 15 C allowed reactivation,
      although to a different extent. Ammonium sulfate was found both to stimulate
      enzyme activity and to reactivate temperature-inactivated enzyme.

PMID- 16562131
TI  - Metabolism of Pipecolic Acid in a Pseudomonas Species IV. Electron Transport
      Particle of Pseudomonas putida.
AB  - Baginsky, Marietta L. (University of California, San Francisco Medical Center,
      San Francisco), and Victor W. Rodwell. Metabolism of pipecolic acid in a
      Pseudomonas species. IV. Electron transport particle of Pseudomonas putida. J.
      Bacteriol. 92:424-432. 1966.-Enzymes of Pseudomonas putida P2 catalyzing
      oxidation of pipecolate to Delta(1)-piperideine-6-carboxylate are located in a
      subcellular fraction sedimenting at 105,000 x g. Since this fraction resembles
      the mammalian electron transport particle in both chemical composition and
      enzymatic activities, it was termed Pseudomonas P2 electron transport particle
      (P2-ETP). P2-ETP contains flavin adenine dinucleotide, flavin mononucleotide,
      iron, copper, and both b- and c-type cytochromes. The reduced type b cytochrome
      has absorption maxima at 558 to 559, 530, and 427 mmu. Its oxidized pyridine
      hemochromogen has an absorption maximum at 406 mmu, with a shoulder at 564 mmu.
      On dithionite reduction, absorption bands with maxima at 556, 522, and 418 mmu
      are obtained. The reduced type c cytochrome has absorption maxima at 552, 520,
      and 422 mmu; its reduced pyridine hemochromogen has maxima at 551, 516 to 519,
      and 418 mmu. No type a cytochrome was detected. P2-ETP catalyzes oxidation of
      pipecolate and of reduced nicotinamide adenine dinucleotide (NADH(2)) by oxygen.
      It can also oxidize these compounds, as well as succinate and reduced
      nicotinamide adenine dinucleotide phosphate, with 2,6-dichlorophenol-indophenol
      as electron acceptor. Mammalian cytochrome c can be used as an alternate
      artificial electron acceptor for the oxidation of pipecolate and succinate, but
      not for oxidation of NADH(2).

PMID- 16562132
TI  - Detection of biologically active adenovirions unable to plaque in human cells.
AB  - Butel, Janet S. (Baylor University College of Medicine, Houston, Tex.), Joseph L.
      Melnick, and Fred Rapp. Detection of biologically active adenovirions unable to
      plaque in human cells. J. Bacteriol. 92:433-438. 1966.-Plaque formation in green
      monkey kidney (GMK) cells by a defective simian virus 40-adenovirus 7 "hybrid"
      population (PARA-adenovirus 7) was enhanced by the addition of excess
      adenovirions. Adenovirus types 2, 7, and 12 were capable of providing
      enhancement, although none of these viruses gives rise to plaques in simian cells
      in the absence of PARA (particle aiding replication of adenovirus). Near maximal
      enhancement of the PARA plaque titer on simian cells was obtained with input
      multiplicities ranging from 0.02 to 0.14 plaque-forming units (PFU) of helper
      adenovirus per GMK cell. The PFU of helper adenoviruses tested (types 2, 7, and
      12) were measured in the most sensitive assay system, human kidney cells. This
      input corresponded to three to nine helper virus particles per GMK cell. The
      majority of particles capable of enhancing plaque formation by PARA banded at a
      density of 1.34 in CsCl. Adenoviruses inactivated by heat or ultraviolet light
      were not capable of enhancing plaque formation by PARA. Highest titers were
      obtained when PARA and helper adenovirus were inoculated simultaneously.
      Inoculation of the helper adenovirus 24 hr prior to the inoculation of PARA
      resulted in the formation of only 50% as many plaques, and no enhanced plaques
      developed when the adenovirus preceded PARA by 48 hr. Conversely, the addition of
      adenovirus 48 hr after the inoculation of PARA initiated 56% as many plaques as
      simultaneous inoculation; 4% of the enhanced plaques still formed when helper
      virus was added as late as 5 days after inoculation of PARA. These results
      suggest that adenovirus particles unable to plaque on human or monkey kidney
      cells are nevertheless capable of interacting with PARA in simian cells, thereby
      facilitating replication of both particles.

PMID- 16562133
TI  - Dietary influence on innate and acquired resistance to tuberculosis.
AB  - Hedgecock, Loyd W. (Veterans Administration Hospital, St. Louis, Mo.). Dietary
      influence on innate and acquired resistance to tuberculosis. J. Bacteriol. 92:439
      445. 1966.-The pattern of deaths of CF1 mice maintained both on a defined ration
      and on commercial chow, and infected with the H37Rv strain of Mycobacterium
      tuberculosis was compared with that of animals infected with four wild strains of
      tubercle bacilli as well as with the Vallee and Ravenel strains of M. bovis. All
      infected animals fed the defined ration died at a slower rate than those fed
      chow. The dietary effects were most evident in the groups of mice infected with
      the human strains of M. tuberculosis at reduced dose levels. Under these
      conditions, a decrease in rate of death occurred in the infected mice fed the
      defined ration at approximately 3 weeks after infection. Deaths in the animals
      infected with the bovine strains and fed the defined ration were distributed
      normally. Interval counts of the number of tubercle bacilli in the lungs of mice
      infected with a reduced dose of the H37Rv strain of M. tuberculosis showed that
      in vivo growth of the organisms was inhibited at 2 weeks in the animals fed the
      defined ration and at 3 weeks in those fed chow. Nonviable vaccines prepared from
      the H37Rv human strain and from the Ravenel and Vallee strains of M. bovis were
      ineffective against infection with the bovine strains. All vaccines were
      effective against infection with the H37Rv strain of M. tuberculosis.

PMID- 16562134
TI  - Metabolism of 6-Mercaptopurine by Resistant Escherichia coli Cells.
AB  - Coggin, Joseph H. (University of Chicago, Chicago, Ill.), Muriel Loosemore, and
      William R. Martin. Metabolism of 6-mercaptopurine by resistant Escherichia coli
      cells. J. Bacteriol. 92:446-454. 1966.-6-Mercaptopurine (MP) utilization as a
      source of purine in MP-sensitive and -resistant cultures of Escherichia coli was
      investigated. The label of MP-8-C(14) appeared in adenine and guanine of
      ribonucleic acid and deoxyribonucleic acid in sensitive and resistant cultures.
      Studies using MP-S(35) further demonstrated that the MP moiety was degraded, as
      shown by a rapid decrease in radioactivity from cells upon exposure to MP for 20
      min. Enzymatic analysis showed that MP was converted to 6-mercaptopurine
      ribonucleotide (MPRP) by extracts derived from both sensitive and resistant
      cells. Resistant cell preparations, however, degraded MPRP to inosine
      monophosphate (IMP) rapidly when compared with analogue degradation by sensitive
      cells. Inosineguanosine-5'-phosphate pyrophosphorylase from resistant cells did
      not catalyze the synthesis of IMP from hypoxanthine when the cells were cultured
      in the presence of MP, but these enzyme preparations actively converted guanine
      to guanosine monophosphate (GMP). Pyrophosphorylase derived from resistant cells
      cultured in medium without MP catalyzed the conversion of hypoxanthine to IMP and
      also guanine to GMP. These observations suggest that inosine-guanosine-5'
      phosphate pyrophosphorylase is composed of two distinct enzymes. The mode of
      resistance to MP in E. coli is related to an enhancement of the enzymatic
      degradation of MPRP to the pivotal purine intermediate, IMP.

PMID- 16562135
TI  - Genetic Recombination of Transforming Deoxyribonucleic Acid Molecules with the
      Recipient Genome and Among Themselves in Protoplasts of Bacillus subtilis.
AB  - Hirokawa, Hideo (Southwest Center for Advanced Studies, Dallas, Tex.), and
      Yonosuke Ikeda. Genetic recombination of transforming deoxyribonucleic acid
      molecules with the recipient genome and among themselves in protoplasts of
      Bacillus subtilis. J. Bacteriol. 92:455-463. 1966.-Re-extraction of transforming
      deoxyribonucleic acid (DNA) from protoplasts of Bacillus subtilis is much more
      efficient than from intact competent cells. This facilitated the detection of
      physical recombination between donor and recipient DNA molecules, as indicated by
      a high cotransfer index of ind(+) and his(+) markers which were originally
      located in exogenous and endogenous DNA molecules, respectively. This recombinant
      DNA was extracted after 30 min of incubation of ind his(+) protoplasts with
      ind(+)his DNA, previously extracted from a corresponding mutant strain of B.
      subtilis. The intracellular formation of recombinant molecules (ind(+)his(+))
      bearing markers from two different exogenous DNA species was also detected 15 min
      after exposure of ind his recipient protoplasts to a mixture of ind(+)his and ind
      his(+) donor DNA molecules. The unity of the recombinant molecule was ascertained
      by dilution experiments and by its being resistant to ribonuclease and trypsin
      treatment (but being sensitive to deoxyribonuclease). The formation of
      recombinant molecules showed an inverse kinetics to that of the intracellularly
      induced loss of linkage between the corresponding markers in the wild-type DNA,
      thus suggesting a breakage and reunion process which is also favored by the
      absence of DNA synthesis in the protoplasts and the effect of some specific
      inhibitors.

PMID- 16562136
TI  - Isolation of a Mutant of Escherichia coli with a Temperature-sensitive Fructose
      1,6-Diphosphate Aldolase Activity.
AB  - Bock, August (Purdue University, Lafayette, Ind.), and Frederick C. Neidhardt.
      Isolation of a mutant of Escherichia coli with a temperature-sensitive fructose
      1,6-diphosphate aldolase activity. J. Bacteriol. 92:464-469. 1966.-A mutant of
      Escherichia coli was isolated which was able to grow in rich medium at 30 C but
      not at 40 C. Upon exposure to 40 C, the cells immediately stopped ribonucleic
      acid (RNA) and deoxyribonucleic acid synthesis, but protein synthesis continued
      at a diminished rate for a short time. Addition of chloramphenicol did not
      release RNA synthesis from inhibition at 40 C. Synthesis of beta-galactosidase
      could be induced at high temperature despite the presence of glucose in the
      medium, indicating a lesion in glucose catabolism. Of many catabolic enzymes
      tested in cell-free extracts, only fructose-1,6-diphosphate aldolase activity
      appeared to be altered in the mutant cells. No activity was demonstrable in
      extracts of mutant cells grown at either 30 or 40 C, but determination of glucose
      oxidation patterns revealed that the enzyme is probably active in vivo at 30 C.
      Temperature-resistant secondary mutants were found to have partially or fully
      restored aldolase activity, and temperature-resistant recombinants had normal
      aldolase activity, indicating that the growth pattern and the altered aldolase
      had a common genetic basis. Linkage data permitted the assignment of an
      approximate map location for the mutated aldolase gene.

PMID- 16562137
TI  - Properties of a Mutant of Escherichia coli with a Temperature-sensitive Fructose
      1,6-Diphosphate Aldolase.
AB  - Bock, August (Purdue University, Lafayette, Ind.), and Frederick C. Neidhardt.
      Properties of a mutant of Escherichia coli with a temperature-sensitive fructose
      1,6-diphosphate aldolase. J. Bacteriol. 92:470-476. 1966.-A mutant of Escherichia
      coli in which fructose-1,6-diphosphate aldolase functions at 30 C but not at 40 C
      was used to study the physiological effect of a specific block in the Embden
      Meyerhof glycolytic pathway. Growth of the mutant at 40 C was found to be
      inhibited by the presence of glucose or certain related compounds in the medium.
      At 40 C, glucose was metabolized at 30 to 40% of the control rate and was
      abnormal in that glucose was converted into other six-carbon substances (probably
      gluconate, in large part) that were released into the culture medium. The
      inhibition was complete, but transient; its duration depended upon the initial
      amount of inhibitor added. The resumption of growth at 40 C was correlated with
      the further catabolism of the excreted compounds. When glycerol was used to grow
      the mutant at 40 C, the growth inhibition by glucose was accompanied by cessation
      of glycerol metabolism. Growth on alpha-glycerol phosphate was not inhibited
      under these conditions, implicating glycerol kinase as a possible site of
      inhibition; no inhibition of glycerol kinase by sugar phosphates, however, could
      be detected in vitro. The inhibitory effect of glucose on growth at 40 C is not
      caused by a deficit of intracellular adenosine triphosphate, but may be the
      result of a generalized poisoning of many cell processes by a greatly increased
      intracellular concentration of fructose-1,6-diphosphate, the substrate of the
      damaged enzyme.

PMID- 16562138
TI  - Episome-mediated Transfer of Drug Resistance in Enterobacteriaceae X. Restriction
      and Modification of Phages by fi R Factors.
AB  - Watanabe, Tsutomu (Keio University, Tokyo, Japan), Toshiya Takano, Toshihiko
      Arai, Hiroshi Nishida, and Sachiko Sato. Episome-mediated transfer of drug
      resistance in Enterobacteriaceae. X. Restriction and modification of phages by
      fi(-) R factors. J. Bacteriol. 92:477-486. 1966.-An fi(-) R factor, which
      restricts phages lambda, T1, and T7 without modifying them, was found to restrict
      and not to modify an F(-)-specific phage, W-31, in Escherichia coli K-12, but not
      to restrict phage P-22 in Salmonella typhimurium LT-2, whereas other fi(-) R
      factors restricted and modified P-22 but not W-31; fi(+) R factors did not
      restrict these phages. Transduction and lysogenization with phages lambda and P
      22 were reduced by these fi(-) R factors in K-12 and LT-2, respectively, and the
      transducing phages lambda and P-22 were modified by these fi(-) R factors.
      Spontaneous as well as ultraviolet-induced production of phage P-22 and zygotic
      induction of phage lambda were not significantly affected by any R factor.
      Injection of the nucleic acids of phages T1 and lambda was not affected by R
      factors, but the injected phage nucleic acids were rapidly broken down in the
      bacteria carrying fi(-) R factors. The nucleic acids of the modified phages were
      not broken down in these bacteria. It was assumed from these results that the
      mechanism of restriction of phages by fi(-) R factors is due to the breakdown of
      the injected phage nucleic acids by a deoxyribonuclease(s), presumably located
      near the cell surface in the cells carrying fi(-) R factors. The
      deoxyribonuclease(s), formed in the cells carrying the nonmodifying fi(-) R
      factor, is considered to be different from that synthesized in the cells carrying
      the modifying fi(-) R factors. It was further shown that the average burst sizes
      of the unmodified as well as modified phages are slightly reduced by the presence
      of the fi(-) R factors.

PMID- 16562139
TI  - Fine Structure of Thiobacillus thiooxidans.
AB  - Mahoney, Robert P. (Skidmore College, Saratoga Springs, N.Y.), and Mercedes R.
      Edwards. Fine structure of Thiobacillus thiooxidans. J. Bacteriol. 92: 487-495.
      1966.-Thin section analysis of the chemosynthetic autotroph Thiobacillus
      thiooxidans revealed structures comparable to gram-negative heterotrophic
      bacteria. Although this species is unique in that it oxidizes elemental sulfur
      for energy, uses carbon dioxide as its sole source of carbon, and can withstand a
      pH of less than 1, thin sections revealed a profile of the cell envelope (cell
      wall and plasmalemma) similar to other gram-negative species which have more
      common physiological traits. The cell wall is composed of five layers with an
      overall width of approximately 200 A, and the plasmalemma appears as a
      conventional "unit membrane" with a width of about 85 A. Volutin granules and
      less-dense bodies of similar shape and size were frequently observed in close
      association with the nucleoplasm. The nature and function of these bodies are
      unknown at this time.

PMID- 16562140
TI  - Lethal gram-negative bacterial superinfection in Guinea pigs given bacitracin.
AB  - Farrar, W. Edmund, Jr. (Walter Reed Army Institute of Research, Washington,
      D.C.), Thomas H. Kent, and Van B. Elliott. Lethal gram-negative bacterial
      superinfection in guinea pigs given bacitracin. J. Bacteriol. 92:496-501. 1966.
      Oral administration of a single dose of bacitracin (either 2,000 or 10,000 units)
      was lethal to more than 80% of guinea pigs. Within the first 12 hr, there was a
      2,000-fold fall in the number of gram-positive organisms in the cecum. An
      increase in the number of coliform bacteria in the cecum was demonstrable within
      6 hr, and, by 48 hr, these organisms had increased from the normal level of less
      than 100 per gram to approximately 1 billion per gram. The changes in intestinal
      bacterial flora were associated with development of a severe cecitis, mild
      ileitis, and acute regional lymphadenitis. Bacteremia, primarily due to coliform
      bacteria, was demonstrated in approximately 40% of the animals killed between 72
      and 96 hr after administration of bacitracin. Development of this disease
      syndrome was suppressed by the administration of neomycin and polymyxin B,
      nonabsorbable antibiotics effective against coliform bacteria. The lethal disease
      produced by bacitracin in the guinea pig is similar to that produced by
      penicillin.

PMID- 16562141
TI  - Growth of Leptospira pomona and Its Effect on Various Tissue Culture Systems.
AB  - Miller, Robert E. (University of Nebraska College of Medicine, Omaha), Norman G.
      Miller, and Roberta J. White. Growth of Leptospira pomona and its effect on
      various tissue culture systems. J. Bacteriol. 92:502-509. 1966.-Leptospira pomona
      strain 3341 was grown in association with primary fetal bovine kidney (PBK) and
      human embryonic skin-muscle fibroblastic (HE) cells in Eagle's minimal essential
      medium (MEM) with 5% sheep serum. Growth curves of leptospires in PBK and HE cell
      cultures showed no substantial increase in growth above that obtained in Eagle's
      MEM in the absence of tissue culture cells. This suggested that no stimulatory
      growth factors for leptospires were produced by the tissue cells. Fibroblastic
      cells of the PBK monolayer showed separation, deterioration, and, finally,
      complete disintegration. Epithelial-like cells remained unaffected. HE cells
      showed the same cytopathic effect as PBK fibroblastic cells, indicating that this
      effect was not limited to PBK fibroblastic cells. Warthin-Starry stains of PBK
      and HE cell monolayers showed masses of leptospires adhering to fibroblastic
      cells, whereas only a few were seen on epithelial-like cells. Large numbers of
      leptospires on the surface of fibroblastic cells are very likely associated with
      the cytopathic effect. Dislodgment of leptospires from fibroblastic cells did not
      increase the total number of spirochetes in the culture. This indicated that
      leptospiral growth did not occur on the surface of these cells.

PMID- 16562142
TI  - Lack of effect of mg on the antistaphylococcal activity of vancomycin.

PMID- 16562143
TI  - Streptococcal fish pathogen.

PMID- 16562144
TI  - Preselection of hemolytic variants of el tor vibrios.

PMID- 16562145
TI  - Deoxyribonucleic Acid Base Composition of Desulfotomaculum nigrificans.

PMID- 16562147
TI  - Thermocins of Bacillus stearothermophilus.

PMID- 16562146
TI  - Genetic suppressors of bacteriophage t5 amber mutants.

PMID- 16562148
TI  - Enhanced Catabolite Repression in Escherichia coli by Growth on Combined
      Substrates.

PMID- 16562149
TI  - Growth-and Fission.

PMID- 16562150
TI  - Use of 3,4-Dihydroxyphenylalanine Oxidation in the Identification of
      Mycobacterium leprae.

PMID- 16562151
TI  - Response of Cell Walls of Escherichia coli to a Sudden Reduction of the
      Environmental Osmotic Pressure.
AB  - The rate of survival after osmotic shocks was found to be dependent on the state
      of growth. When growing logarithmically, Escherichia coli was about 20 to 100
      times more sensitive to an abrupt decrease of the environmental osmotic pressure
      than when it was in the stationary phase. Subjecting rapidly growing cells to
      such a treatment caused fingerlike extrusions to emerge from the bacterial wall.
      Our results suggest that underneath these extrusions the rigid layer of the wall
      contains weak areas which appear as discontinuities or gaps when viewed in an
      electron microscope. After exposure to osmotic shock, the gaps became wider. We
      concluded that the gaps represent sites of mucopolymer synthesis where the rigid
      structure has temporarily been opened by hydrolytic enzymes to allow for the
      insertion of new wall material into the older portions of the wall.

PMID- 16562152
TI  - Metabolic Activity of the Trench Fever Rickettsia, Rickettsia quintana.
AB  - A study of the metabolic activity of Rickettsia quintana was carried out by
      conventional Warburg and radioisotope techniques with intact cells harvested
      while growing in the fluid counterpart of the medium of Vinson and Fuller. Like
      other rickettsiae, R. quintana did not utilize glucose, but did metabolize
      glutamate and glutamine. Unlike typhus rickettsiae, R. quintana did not require a
      diluent high in K(+) for metabolic activity, and it utilized glutamine more
      efficiently than glutamate. In typical experiments, this microorganism produced
      1.6 to 2.0 mumoles of CO(2) from glutamine per mg of rickettsial protein per hr
      at 37 C, while consuming 1.5 to 1.7 mumoles of O(2). R. quintana also utilized,
      in descending order, succinate, alpha-ketoglutarate, glutamate, pyruvate, and
      citrate; the first-named substrate was utilized more rapidly than glutamine. R.
      quintana, like typhus rickettsiae, has a glutamate-oxaloacetate transaminase
      because aspartate was isolated, by means of thin-layer chromatography, as one of
      the end products of the utilization of glutamine. When the microorganisms were
      incubated with glutamine-(14)C and unlabeled intermediates of the citric acid
      cycle, labeled dicarboxylic acids of the cycle were recovered. Labeled
      tricarboxylic acids, however, were not recovered, possibly because of cellular
      impermeability to the corresponding unlabeled intermediates. In the case of cis
      aconitate, it was shown that this substrate interfered with the uptake of
      glutamine. These observations are believed to provide convincing evidence that
      glutamine is utilized through the citric acid cycle and that R. quintana, with
      the differences noted, resembles other rickettsiae.

PMID- 16562153
TI  - CO(2) Fixation, Glutamate Labeling, and the Krebs Cycle in Ribose-grown
      Hydrogenomonas facilis.
AB  - Exposure of ribose-grown Hydrogenomonas facilis to (14)CO(2) for 6 to 12 sec
      during ribose oxidation resulted in labeling of a number of compounds, three of
      which were glutamate, phosphoglycerate, and pyruvate. Phosphoglycerate and
      pyruvate were labeled almost exclusively in C(1), suggesting operation of the
      reductive pentose phosphate cycle. Glutamate was labeled initially to the extent
      of 90% in C(1) and 10% in C(5), and this was followed by a concentration of
      radioisotope in C(5). All of the enzymes of the tricarboxylic acid cycle were
      detectable in ribose-grown cells, and, in general, specific activities were
      similar to those found in yeast extract-grown cells. Reduced nicotinamide adenine
      dinucleotide oxidase, aconitase, and the dehydrogenases for pyruvate, alpha
      ketoglutarate, and succinate appeared to be of particulate origin. In addition to
      enzymes of the tricarboxylic acid cycle, an acetyl coenzyme A-stimulated
      phosphoenolpyruvate carboxylase was found, as was isocitrate lyase. Possible
      participation of these catalysts in glutamate synthesis is discussed.

PMID- 16562154
TI  - Glucose-induced Release of Amino Acids from Saccharomyces carlsbergensis by
      Action on the Cytoplasmic Membrane.
AB  - When washed yeast cells grown under appropriate conditions were suspended in
      glucose solution there was a sudden release of alpha-amino nitrogen into the
      medium. This released material was of low molecular weight, and its composition
      was closely similar to that of the intracellular free amino acid pool. During the
      leakage of amino acids, the yeast did not efficiently absorb labeled amino acids
      added to the test medium, despite the rapid uptake and metabolism of glucose.
      Uptake of a labeled amino acid and reabsorption of the released alpha-amino
      nitrogen occurred almost simultaneously. When these yeast cells were exposed to
      glucose in the presence of calcium ions, leakage was strongly inhibited. Butanol
      under the same conditions increased glucose-induced leakage of cell contents. The
      adenosine triphosphatase activity of intact yeast cells exposed to glucose was
      greater than that of cells exposed to water. Yeast cells treated with glucose
      prior to equilibration with sorbose exhibited less ability to retain the sorbose
      when washed at 0 C than did cells pretreated with water. It was concluded that
      glucose-induced leakage of amino acids was the result of two factors acting
      together. These were (i) a change in membrane permeability associated with
      glucose uptake, and (ii) a temporary shortage of energy for amino acid uptake or
      retention.

PMID- 16562155
TI  - Virulence of Escherichia coli Serotypes for Mice.
AB  - A study was undertaken to determine whether virulence in mice could be used to
      assess the pathogenicity of a variety of Escherichia coli serotypes. Sixty-one E.
      coli strains isolated from animals, poultry, or humans were serotyped to
      determine their O, K, and H antigens, and were administered to mice via the
      intraperitoneal route with and without a mucin adjuvant. The ld(50) dose was then
      determined for each serotype. The results indicated that the source of the
      serotype may be associated with virulence for mice. Serotypes isolated from
      nonenteric, systemic sources showed a greater virulence for mice inoculated
      intraperitoneally than did the enteric and the nonenteric, nonsystemic
      (localized) isolates. It was observed that not all serotypes belonging to a
      specific serogroup were virulent for mice and that the presence or absence of a K
      antigen had no effect on the virulence of strains of one serotype.

PMID- 16562156
TI  - Localization of indigenous yeast in the murine stomach.
AB  - Certain strains of yeast were cultured frequently from the feces of adult CFW
      mice and Long-Evans and Sprague-Dawley rats, but not from infants of those murine
      strains, or from adults or infants of NCS or NCS-D mice. When the yeasts could be
      cultured from the feces, they could also be grown from all areas of the digestive
      tracts of the animals, but especially from the stomachs, where they formed layers
      on the epithelium of the glandular mucosa. Three of the yeast isolates, one each
      from the three murine colonies, were provisionally classified in the genus
      Torulopsis of the asporogenous yeasts. These yeast strains failed to colonize the
      digestive tubes of suckling infant mice of either the CFW or NCS-D colonies. In
      contrast, they colonized the guts of adult NCS-D mice and formed layers in their
      stomachs; tests with the yeast from CFW mice revealed that this strain colonized
      the guts and formed layers in the stomachs of germ-free CFW mice. When
      established in NCS-D mice, the yeast strains did not affect qualitatively or
      quantitatively the growth of the animals or the composition of the bacterial
      flora in the gastrointestinal tracts. Moreover, they did not elicit an unusual
      inflammatory response in the digestive tracts; nor were they pathogenic for NCS
      mice when injected by the intraperitoneal or intravenous routes. The yeasts thus
      appear to be harmless saprophytes that are able to flourish in the environment of
      the surface of the secreting epithelium of the murine stomach. The findings
      conform with the view that some types of microorganisms of the gastrointestinal
      tract are not just mixed randomly but rather occupy microenvironments in almost
      pure culture. This concept is important to the understanding of the ecology of
      the gut microflora.

PMID- 16562157
TI  - Effect of Substrate on the Fatty Acid Composition of Hydrocarbon- and Ketone
      utilizing Microorganisms.
AB  - The fatty acid pattern in hydrocarbon- and ketone-utilizing bacteria after growth
      on various substrates was examined. The fatty acid composition of one hydrocarbon
      utilizing organism (Mycobacterium sp. strain OFS) was investigated in detail
      after growth on n-alkanes, 1-alkenes, ketones, and n-alcohols. n-Alkanes shorter
      than C(13) or longer than C(17) were not incorporated into cellular fatty acids
      without some degradation. Strain OFS incorporated C(14) to C(17) 1-alkenes into
      cellular fatty acids as the omega-monoenoic fatty acid. Methyl ketones were
      incorporated into strain OFS after removal of one- or two-carbon fragments from
      the carbonyl end of the molecule. An organism isolated by enrichment on methyl
      ketones was incapable of n-alkane utilization but could grow on, although not
      incorporate, ketones or long chain n-alcohols into cellular fatty acids.

PMID- 16562158
TI  - Proflavine Uptake and Release in Sensitive and Resistant Escherichia coli.
AB  - Both Escherichia coli B and a proflavine-resistant mutant, E. coli B/Pr, took up
      the same amounts of proflavine when suspended in buffer containing the dye. In
      growth media, however, sensitive cells took up more proflavine than did resistant
      cells. Adding growth media or any one of several constituents of these media,
      including amino acids, glycerol, pyruvic acid, and metabolizable sugars, to
      resistant cells that had taken up proflavine in buffer caused them to lose the
      dye, but had less or no effect on sensitive cells. Certian salts caused an equal
      release of proflavine from resistant and sensitive cells. Proflavine released
      from resistant cells by glucose was not changed chemically. The effects of
      temperature and metabolic inhibitors suggest that proflavine uptake is a passive
      process but that its release may be an active one, dependent on metabolism.
      Glucose had more effect on the proflavine binding of E. coli B grown in a minimal
      medium than on that of cells grown in a complex medium. E. coli B was less
      susceptible to proflavine when growing in a minimal medium. The effects of other
      synthetic media on proflavine susceptibility of E. coli B were also studied.
      Deoxyribonucleic acid and envelopes from sensitive and resistant cells bound the
      same amounts of proflavine, and no difference was seen in the site of dye binding
      when sensitive and resistant cells that had taken up proflavine in buffer were
      sonically broken and fractionated. The results suggest that sensitive and
      resistant cells are equally permeable to proflavine but differ in the ease with
      which metabolites cause them to release bound proflavine. So far, however, these
      differences do not account completely for the ability of resistant cells to grow
      in high proflavine concentrations.

PMID- 16562160
TI  - Editorial.

PMID- 16562159
TI  - Specificity of Acquired Resistance Produced by Immunization with Listeria
      monocytogenes and Listeria Fractions.
AB  - Mice were immunized with 1.0 mg of an attenuated strain of Listeria monocytogenes
      to determine the period of protection afforded by this strain when the mice were
      challenged intravenously with 5 MLD of listeria. Protection appeared 2 days after
      immunization and was still apparent 4 weeks after immunization. If the challenge
      dose was decreased to 1 MLD, protection was apparent at 10 weeks. Mice immunized
      with a comparable dose of mycobacterial cells and challenged intravenously with 1
      MLD of listeria showed no protection at 10 weeks. The magnitude of the immune
      response to listeria challenge was not increased in mice immunized with the same
      virulent strain as that used for challenge. It was also found that resistance to
      listeria challenge appeared early after listeria immunization if the immunizing
      dose was large. As the immunizing dose was decreased and the challenge dose
      increased, resistance appeared later. Listeria killed by heat or ultraviolet
      irradiation, living but nonmultiplying streptomycin-dependent listeria, or
      listeria ribosomal fraction gave no protection against listeria challenge. The
      magnitude of the immune responses after listeria immunization to listeria
      challenge and to mycobacteria challenge were compared. It was found that
      protection after listeria challenge was of longer duration. In addition, a 100
      fold larger vaccinating dose was required to give comparable protection against
      tuberculous infection.

PMID- 16562162
TI  - Editorial.

PMID- 16562161
TI  - Editorial.

PMID- 16562164
TI  - In memory of harold weintraub.

PMID- 16562163
TI  - Editorial.

PMID- 16562166
TI  - Editorial.

PMID- 16562165
TI  - Editorial.

PMID- 16562167
TI  - Editorial note.

PMID- 16562168
TI  - Molecular Biology of the Cell: It's Our Journal.

PMID- 16562169
TI  - Cambridge University History of Medicine Society.

PMID- 16562171
TI  - The Osler Club of London.

PMID- 16562170
TI  - The Norwegian Society for the History of Medicine.

PMID- 16562172
TI  - Royal Society of Medicine Section of the History of Medicine.

PMID- 16562173
TI  - The Scottish Society of the History of Medicine.

PMID- 16562174
TI  - News from Scotland.

PMID- 16562175
TI  - Cambridge University History of Medicine Society.

PMID- 16562176
TI  - The Norwegian Society for the History of Medicine.

PMID- 16562177
TI  - The Osler Club of London.

PMID- 16562178
TI  - Harvey Tercentenary Congress, 1957.

PMID- 16562180
TI  - The Osler Club of London.

PMID- 16562179
TI  - Cambridge University History of Medicine Society.

PMID- 16562182
TI  - Royal Society of Medicine Section of the History of Medicine.

PMID- 16562181
TI  - The Norwegian Society for the History of Medicine.

PMID- 16562183
TI  - The Scottish Society of the History of Medicine.

PMID- 16562184
TI  - Society Reports.

PMID- 16562185
TI  - JOHN HUNTER AND AN AMPUTATION UNDER ANALGESIA IN 1784.

PMID- 16562186
TI  - Society Reports.

PMID- 16562187
TI  - Society Reports.

PMID- 16562188
TI  - Cambridge University History of Medicine Society.

PMID- 16562190
TI  - Section of Medical History in the British Medical Association (Victorian Branch).

PMID- 16562189
TI  - Norwegian Society for the History of Medicine.

PMID- 16562191
TI  - The Scottish Society of the History of Medicine.

PMID- 16562192
TI  - Norwegian Society for the History of Medicine.

PMID- 16562194
TI  - PRIZE ESSAY COMPETITION.

PMID- 16562193
TI  - THE SCOTTISH SOCIETY OF THE HISTORY OF MEDICINE.

PMID- 16562195
TI  - British Medical Association (Victorian Branch) Section of Medical History.

PMID- 16562196
TI  - Norwegian Society for the History of Medicine.

PMID- 16562197
TI  - The Osler Club of London.

PMID- 16562198
TI  - Cambridge University History of Medicine Society.

PMID- 16562199
TI  - NORWEGIAN SOCIETY FOR THE HISTORY OF MEDICINE.

PMID- 16562201
TI  - FACULTY OF THE HISTORY OF MEDICINE AND PHARMACY WORSHIPFUL SOCIETY OF
      APOTHECARIES.

PMID- 16562200
TI  - SECTION OF MEDICAL HISTORY IN THE BRITISH MEDICAL ASSOCIATION (Victorian Branch).

PMID- 16562202
TI  - SECTION OF MEDICAL HISTORY IN THE BRITISH MEDICAL ASSOCIATION (VICTORIAN BRANCH).

PMID- 16562203
TI  - HARVEY: THE SCENE OF HIS LAST YEARS AND HOURS.

PMID- 16562204
TI  - Cambridge University History of Medicine Society.

PMID- 16562205
TI  - Norwegian Society for the History of Medicine.

PMID- 16562206
TI  - Section of Medical History in the British Medical Association (victorian branch).

PMID- 16562208
TI  - Society Reports.

PMID- 16562207
TI  - JOHN BRAXTON HICKS (1823-1897).

PMID- 16562209
TI  - MEDICINE- MOTHER OF THE SCIENCES.

PMID- 16562210
TI  - MEDICAL RECORDS OF DARTMOUTH, 1425-1887: A contribution to the history of medical
      practice.

PMID- 16562211
TI  - To Our Readers.

PMID- 16562212
TI  - SIR JAMES MACKENZIE AND CELLULAR PATHOLOGY.

PMID- 16562213
TI  - Cambridge University History of Medicine Society.

PMID- 16562214
TI  - Section of Medical History in the British Medical Association (Victorian Branch).

PMID- 16562215
TI  - King's College Hospital Historical Society.

PMID- 16562216
TI  - Norwegian Society for the History of Medicine.

PMID- 16562217
TI  - AN EIGHTEENTH-CENTURY NAVAL SHIP TO ACCOMMODATE WOMEN NURSES.

PMID- 16562218
TI  - Norwegian Society for the History of Medicine.

PMID- 16562219
TI  - ALEXANDER MONRO SECUNDUS AND THE INTERVENTRICULAR FORAMEN.

PMID- 16562220
TI  - Society Reports.

PMID- 16562221
TI  - THE ANTIQUITY OF CAESAREAN SECTION WITH MATERNAL SURVIVAL: THE JEWISH TRADITION.

PMID- 16562222
TI  - COUNTRY PRACTICE IN DAYS GONE BY (as recorded in contemporary diaries) PART II:
      3. THE WOODFORDE DIARY.

PMID- 16562223
TI  - Society Reports.

PMID- 16562224
TI  - EIGHTEEN YEARS OF VESALIAN STUDIES.

PMID- 16562225
TI  - THE APOTHECARIES OF THE GENERAL INFIRMARY AT LEEDS.

PMID- 16562226
TI  - HISTORY OF SURGERY AND INTRODUCTION TO SURGICAL LECTURES, BY MONRO PRIMUS.

PMID- 16562228
TI  - THOMAS SPENCER COBBOLD AND BRITISH PARASITOLOGY.

PMID- 16562227
TI  - Society Reports.

PMID- 16562229
TI  - Society Reports.

PMID- 16562231
TI  - THE CATTLE PLAGUE OF 1865.

PMID- 16562230
TI  - JOHN HASLAM: HIS WILL AND HIS DAUGHTER.

PMID- 16562232
TI  - JOHN FARRE (1775-1862) AND OTHER NINETEENTH CENTURY PHYSICIANS AT MOORFIELDS.

PMID- 16562234
TI  - SOCIETY OF APOTHECARIES: FACULTY OF THE HISTORY OF MEDICINE AND PHARMACY.

PMID- 16562233
TI  - ROBERT TALBOR, CHARLES II, AND CINCHONA A CONTEMPORARY DOCUMENT.

PMID- 16562235
TI  - THE NORWEGIAN SOCIETY FOR THE HISTORY OF MEDICINE.

PMID- 16562236
TI  - PROCEEDINGS OF THE SECTION OF MEDICAL HISTORY IN THE BRITISH MEDICAL ASSOCIATION
      (VICTORIAN BRANCH).

PMID- 16562237
TI  - UNIVERSITY OF CAPE TOWN: MEDICAL HISTORY CLUB.

PMID- 16562238
TI  - THOMAS SYDENHAM (1624-1689) REFORMER OF CLINICAL MEDICINE.

PMID- 16562240
TI  - Society Reports.

PMID- 16562239
TI  - APOTHECARIES, DISPENSERS, STUDENTS AND NINETEENTH-CENTURY PHARMACY AT ST.
      GEORGE'S HOSPITAL, LONDON.

PMID- 16562242
TI  - Society Report.

PMID- 16562241
TI  - THE HUNTERIAN MUSEUM.

PMID- 16562243
TI  - THE IMPACT OF TUBERCULOSIS ON HISTORY, LITERATURE AND ART.

PMID- 16562245
TI  - THE ALBINISM OF TIMUR, ZAL, AND EDWARD THE CONFESSOR.

PMID- 16562244
TI  - MEDICAL REFERENCES IN THE FAMILIAR LETTERS OF JAMES HOWELL.

PMID- 16562246
TI  - BOERHAAVE'S BIOCHEMISTRY.

PMID- 16562247
TI  - THE PERSONNEL AND PRACTICE OF MEDICINE IN TUDOR AND STUART ENGLAND PART I. THE
      PROVINCES.

PMID- 16562248
TI  - THOMAS BEVILL PEACOCK'S LIBRARY.

PMID- 16562249
TI  - A POSSIBLE CASE OF LEPROSY FROM A SAXON CEMETERY AT BECKFORD.

PMID- 16562251
TI  - BRITISH AND FOREIGN MEDICAL REVIEW 1836-47.

PMID- 16562250
TI  - FIRST AUSTRALIAN MEDICAL CONGRESS : section of the history of medicine.

PMID- 16562252
TI  - PUBLIC HEALTH AT THE PRIVY COUNCIL 1805-6.

PMID- 16562253
TI  - Faculty of the History of Medicine and Pharmacy Third British Congress on the
      History of Medicine and Pharmacy.

PMID- 16562254
TI  - The Veterinary History Society.

PMID- 16562255
TI  - The Lindsay Club.

PMID- 16562256
TI  - THOMAS TROTTER, M.D., NAVAL PHYSICIAN.

PMID- 16562257
TI  - THROMBO-EMBOLIC DISEASE AND HEART-BLOCK IN VESALIUS.

PMID- 16562258
TI  - Society Reports.

PMID- 16562259
TI  - Society Reports.

PMID- 16562261
TI  - The Scottish Society of the History of Medicine: Report of Proceedings, 1963-4.

PMID- 16562260
TI  - East London Hospital for Children.

PMID- 16562262
TI  - SOME NOTES ON ANGLO-SAXON MEDICINE.

PMID- 16562263
TI  - EXTRACTS FROM THE DIARY OF THOMAS LAYCOCK: Chiefly written when he was a medical
      student 1833-5.

PMID- 16562264
TI  - CORRESPONDENCE BETWEEN SIR WILLIAM GOWERS AND SIR VICTOR HORSLEY.

PMID- 16562265
TI  - Important Notice.

PMID- 16562267
TI  - Successful errors and other odd ways to new discoveries.

PMID- 16562266
TI  - The ;introduction' to carl ludwig's textbook of human physiology.

PMID- 16562268
TI  - Sir george baker and the devonshire colic.

PMID- 16562269
TI  - An early account of aortic incompetence by Thomas cuming (1798-1887).

PMID- 16562270
TI  - Giles gaudineau and his medicines.

PMID- 16562271
TI  - Anatomical fugitive sheets with superimposed flaps, 1538-1540.

PMID- 16562272
TI  - Persian gynaecology.

PMID- 16562273
TI  - Max neuburger.

PMID- 16562274
TI  - The Scottish society of the history of medicine: report of proceedings, session
      1971-72.

PMID- 16562275
TI  - Reply by Thomas McKeown.

PMID- 16562276
TI  - Letter to the editor.

PMID- 16562278
TI  - Editorial note.

PMID- 16562277
TI  - Doctor david livingstone.

PMID- 16562279
TI  - "Priest-doctors" as a rural health service in the age of Enlightenment.

PMID- 16562280
TI  - Some notes for the history of typhus in Ethiopia.

PMID- 16562281
TI  - The colchester medical society, 1774.

PMID- 16562286
TI  - Lord cohen of birkenhead, C.h., f.R.C.p.

PMID- 16562285
TI  - James Lind and the prevention of scurvy.

PMID- 16562282
TI  - The soldier's friend-Sir Jeremiah Fitzpatrick, Inspector of Health for Land
      Forces.

PMID- 16562288
TI  - Illustrations from the Wellcome Institute Library: A note on the botanical prints
      and drawings.

PMID- 16562284
TI  - Innocent III and the evolution of anatomy.

PMID- 16562287
TI  - Edwin clarke at the wellcome institute.

PMID- 16562289
TI  - Essay review.

PMID- 16562290
TI  - Essay review.

PMID- 16562283
TI  - Notes on some plague paintings.

PMID- 16562292
TI  - Fifty years of the Wellcome Trust.

PMID- 16562291
TI  - Marriage, sex, and the family in England, 1660-1800.

PMID- 16562293
TI  - A vision of history: the wellcome institute for the history of medicine.

PMID- 16562294
TI  - Medical fringe and medical orthodoxy 1750-1850.

PMID- 16562295
TI  - A descriptive and analytical catalogue of Persian manuscripts in the Library of
      the Wellcome Institute for the History of Medicine.

PMID- 16562296
TI  - Classics of cardiology.

PMID- 16562298
TI  - In sickness and in health: the British experience, 1650-1850.

PMID- 16562297
TI  - Photographing medicine: image and power in Britain and America since 1840.

PMID- 16562299
TI  - The uses of experiment: studies in the natural sciences.

PMID- 16562300
TI  - Akute Krankheiten. Chronische Krankheiten, pt. 1: Akute Krankheiten, bks 1-3,
      Chronische Krankheiten, bks 1-2.

PMID- 16562301
TI  - Health for sale: quackery in England, 1660-1850.

PMID- 16562302
TI  - New developments at the Wellcome Institute.

PMID- 16562303
TI  - The price of health: Australian governments and medical politics 1910-1960.

PMID- 16562304
TI  - Framing disease: studies in cultural history.

PMID- 16562305
TI  - Melancholy and society.

PMID- 16562307
TI  - Children of Islam: concepts of childhood in medieval Muslim society.

PMID- 16562306
TI  - Laboratory politics.

PMID- 16562308
TI  - A history of hypnotism.

PMID- 16562309
TI  - Companion encylopedia of the history of medicine.

PMID- 16562310
TI  - From India to the planet Mars: a case of multiple personality with imaginary
      languages.

PMID- 16562311
TI  - On talks.

PMID- 16562312
TI  - Salud, cultura y sociedad en America Latina.

PMID- 16562313
TI  - Images of bodily transformation.

PMID- 16562314
TI  - Le legs de Claude Bernard.

PMID- 16562315
TI  - The history of Bethlem.

PMID- 16562316
TI  - Public health and social justice in the age of Chadwick: Britain, 1800-1854.

PMID- 16562317
TI  - Preface: situating "alternative medicine" in the modern period.

PMID- 16562318
TI  - Rejoinder.

PMID- 16562319
TI  - A new millennium.

PMID- 16562320
TI  - Margaret esther rowbottom 1908-1999.

PMID- 16562321
TI  - The Wellcome Trust Centre for the History of Medicine at UCL.

PMID- 16562322
TI  - On the fabric of the human body. Books I and II, translation by William Frank
      Richardson in collaboration with John Burd Carman.

PMID- 16562323
TI  - Marianne winder.

PMID- 16562324
TI  - The Cambridge world history of food.

PMID- 16562325
TI  - The evolution of British general practice, 1850-1948.

PMID- 16562326
TI  - Some ways into the new millennium.

PMID- 16562328
TI  - Cooking up fine remedies: on the culinary aesthetic in a sixteenth-century
      Chinese Materia Medica.

PMID- 16562329
TI  - Breast cancer and the politics of abortion in the United States.

PMID- 16562330
TI  - Dentistry and the University of London.

PMID- 16562331
TI  - What tuberculosis did for modernism: the influence of a curative environment on
      modernist design and architecture.

PMID- 16562332
TI  - The medical skills of the Malabar doctors in Tranquebar, India, as recorded by
      surgeon T L F Folly, 1798.

PMID- 16562333
TI  - Editorial.

PMID- 16562334
TI  - Racism, poverty, sexism all play a role in epidemic's spread among black women.
      New resource guide educates on problem.
AB  - Health care providers and public health officials note the continuing problems of
      HIV transmission among African American women. They cite sexism, poverty, racism
      as factors that contribute to its devastating path among black women from the
      urban areas of New York City to the rural areas of North Carolina.

PMID- 16562335
TI  - Some PIs have greater impact than others on heart disease. Patients on atazanavir
      had less heart problems.
AB  - Recent research has highlighted the cardiovascular problems that some HIV
      patients have had while being treated with protease inhibitors (PIs), but it's
      been difficult for physicians to determine exactly which drugs are causing the
      most trouble. Now a new study, presented at the 45th Interscience Conference on
      Antimicrobial Agents and Chemotherapy (ICAAC), held Dec. 16-19, 2005, in
      Washington, DC, shows that there is a significant difference in coronary risk
      depending on which PI a patient takes. Investigators found that patients
      receiving atazanavir had a significantly lower risk over a 10-year period of
      coronary heart disease than did patients receiving nelfinavir, and this lower
      risk remained statistically significant for patients who had other heart disease
      risk factors, including smoking, diabetes, and hypertension.

PMID- 16562336
TI  - Clinical reminder might assist physicians in deciding when to offer HIV testing.
      Created through collaborative effort at VA hospital.
AB  - Investigators have developed a clinical reminder that provides clinicians with a
      simple guide to when it's important to offer HIV testing to patients.

PMID- 16562337
TI  - Research helps identify those at risk for non-adherence. Identify those at risk
      using 3 elements.
AB  - Behavioral compliance interventions typically are time-consuming and costly, but
      it might work more efficiently if clinicians quickly could identify the patients
      most in need of such assistance.

PMID- 16562338
TI  - HIV patients taking antiretrovirals should avoid garlic, St. John's wort. Other
      health products were fine.
AB  - Many people infected with HIV look to natural health products to supplement their
      conventional medical care, and clinicians, understandably, are concerned about
      drug interactions.

PMID- 16562339
TI  - Study of efavirenz over 96 weeks shows durability, efficacious regimen. Results
      from 48-96 weeks essentially same.
AB  - Recent results from the Daily Antiretroviral Therapy (DART 1) trial show
      promising results for antiretroviral naive patients. The 96-week study results
      from 65 patients who were treated with the combination of once-daily efavirenz
      (600 mg), lamivudine (300 mg), and didanosine (400 mg) showed that the rates of
      patients achieving HIV-1 RNA viral loads of less than 400 copies were essentially
      the same as the previous 48-week results.

PMID- 16562340
TI  - FDA notifications. FDA grants tentative approval to generic Nevirapine.

PMID- 16562341
TI  - FDA notifications. FDA grants tentative approval to generic stavudine.

PMID- 16562342
TI  - FDA approves new rotavirus vaccine...and hope for a bird flu vaccine?

PMID- 16562343
TI  - Child safety. Paper shredders: a hazard to toddlers.

PMID- 16562344
TI  - Depression in pregnancy: risks to mother...and to her baby: neonatal abstinence
      syndrome...and serious respiratory problems.

PMID- 16562346
TI  - Product recalls. Recalls: first years liquid-filled teethers pose infection
      hazard...and baby walkers are recalled because of stairway hazards.

PMID- 16562345
TI  - Reminder: TV turnoff week is coming!

PMID- 16562347
TI  - Regional bond strengths of a dual-cure resin core material to translucent quartz
      fiber post.
AB  - PURPOSE: To evaluate the microtensile bond strength (muTBS) of a dual-cure resin
      core material to different regions of translucent quartz fiber post in a post
      cavity using different surface treatments. METHODS: 30 translucent quartz fiber
      posts (Light-Post) were used and divided into six groups according to the surface
      treatments: (1) no surface treatment (Control); (2) photo-cure bonding agent,
      Clearfil Liner Bond 2V Bond A (PLB); (3) dual-cure bonding agent, Clearfil Liner
      Bond 2V Bond A+B (DLB); (4) BdA+B followed by light-cured for 20 seconds (DLB &
      LC); (5) silane coupling bonding agent, Clearfil Photobond with Porcelain Bond
      Activator (PB+PBA); (6) PB+PBA followed by light-cure for 20 seconds (PB+PBA&LC).
      Treated post were cemented into artificial post cavities using a dual-cure
      composite core material (Clearfil DC Core) and light-cured for 60 seconds from
      the top of the cavity. After 24-hour storage in water, each specimen was serially
      sliced into twelve 0.6 x 0.6 mm-thick beams for the muTBS test. The data were
      divided into three regions (upper/middle/bottom) and analyzed using two-way ANOVA
      and Dunnet's T3 multiple comparisons (alpha = 0.05). RESULTS: The highest bond
      strength was present in the silane coupling bonding agent group for all regions
      (P < 0.05). Application of the bonding agent to the post surface significantly
      improved the bond strength compared with control (P < 0.05). There were no
      significant differences in muTBS at all regions between the photo and dual-cure
      type bonding agents (P < 0.05). The bond strength significantly decreased at the
      bottom region when the post surface was treated with bonding agents (P < 0.05),
      whereas no regional differences in bond strength were found in the silane
      coupling bonding agent group (P > 0.05).

PMID- 16562348
TI  - How important are psychosocial predictors of mammography receipt among older
      women when immediate access is provided via on-site service?
AB  - PURPOSE: The purpose of the study was to examine the relative importance of
      psychosocial variables (i.e., health beliefs, knowledge, barriers) in predicting
      mammogram receipt compared with providing access through a mobile mammography
      unit among older women who participated in a mobile mammography intervention.
      DESIGN: The data were collected during a randomized trial involving 499 women (60
      to 84 years old) recruited from 60 community sites. SETTING: The study was
      conducted at 60 sites in Los Angeles where seniors gather, including meal sites,
      senior centers, and recreational clubs. SUBJECTS: Participants were older women
      (60 to 84 years old) who spoke English or Spanish, had a telephone, had no
      significant cognitive deficits, and had not received a mammogram during the past
      12 months. MEASURES: The baseline survey assessed demographics and psychosocial
      factors (i.e., health beliefs, knowledge, barriers). A follow-up telephone survey
      at 3 months assessed mammography receipt. RESULTS: Results support the importance
      of behavioral intentions in predicting mammogram receipt, even among women able
      to access a mammogram through the mobile unit. However, other recognized
      psychosocial factors failed to predict screening receipt among women randomized
      to the mobile mammography intervention. Results suggest that the importance of
      psychosocial predictors might be diminished when a major access barrier has been
      removed, and they highlight the importance of convenience. CONCLUSION: Future
      interventions should focus on not only removing obvious concrete and psychosocial
      barriers but also on enhancing convenience.

PMID- 16562349
TI  - [The 65th annual meeting of the Japan Radiological Society. Yokohama,  Japan.
      April 7-9, 2006. Abstracts].

PMID- 16562350
TI  - Taking biology seriously: the next task for historians of addiction?
AB  - Despite more than a century of attempts to control the use of addictive
      substances, prevalence rates continue to grow for most of them. Exceptions are
      tobacco and alcohol use, which, nevertheless, remain major public health
      concerns. Why have these attempts at drug control had little success? This
      question is addressed in the histories of substance use that are examined in this
      essay. While these studies show that there are multiple histories, definitions,
      and frames of addiction that have shifted over time, some broad themes emerge.
      Foremost is the argument that the classification of a substance as licit or
      illicit has had more to do with cultural values than with the substance itself.
      Historians, skeptical of essentialist categories, have questioned whether
      addictions are diseases and the wisdom of selectively criminalizing drug use.
      They argue that the socioeconomic status of users has influenced attitudes toward
      addicts and the legal classifications of substances.

PMID- 16562351
TI  - [The 103rd meeting of the Japanese Society of Internal Medicine. Yokohama, Japan.
      April 14-16, 2006. Abstracts].

PMID- 16562352
TI  - The Web as an educational tool for/in learning/teaching bioinformatics
      statistics.
AB  - Statistics provides essential tool in Bioinformatics to interpret the results of
      a database search or for the management of enormous amounts of information
      provided from genomics, proteomics and metabolomics. The goal of this project was
      the development of a software tool that would be as simple as possible to
      demonstrate the use of the Bioinformatics statistics. Computer Simulation Methods
      (CSMs) developed using Microsoft Excel were chosen for their broad range of
      applications, immediate and easy formula calculation, immediate testing and easy
      graphics representation, and of general use and acceptance by the scientific
      community. The result of these endeavours is a set of utilities which can be
      accessed from the following URL: http://gmein.uib.es/bioinformatica/statistics.
      When tested on students with previous coursework with traditional statistical
      teaching methods, the general opinion/overall consensus was that Web-based
      instruction had numerous advantages, but traditional methods with manual
      calculations were also needed for their theory and practice. Once having mastered
      the basic statistical formulas, Excel spreadsheets and graphics were shown to be
      very useful for trying many parameters in a rapid fashion without having to
      perform tedious calculations. CSMs will be of great importance for the formation
      of the students and professionals in the field of bioinformatics, and for
      upcoming applications of self-learning and continuous formation.

PMID- 16562353
TI  - Medical devices; immunology and microbiology devices; classification of reagents
      for detection of specific novel influenza A viruses. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying Reagents for detection of
      specific novel influenza A viruses into class II (special controls). Special
      controls that will apply to the device are the guidance document entitled, "Class
      II Special Controls Guidance Document: Reagents for Detection of Specific Novel
      Influenza A Viruses" and limitations of distribution of these reagents. The
      agency is taking this action in response to a petition submitted under the
      Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device
      Amendments of 1976, the Safe Medical Devices Act of 1990, the Food and Drug
      Administration Modernization Act of 1997, and the Medical Device User Fee and
      Modernization Act of 2002. The agency is classifying the device into class II
      (special controls) in order to provide a reasonable assurance of safety and
      effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA
      is publishing a notice of availability of a guidance document that is a special
      control for this device.

PMID- 16562354
TI  - Genetic testing.

PMID- 16562355
TI  - Cloning.

PMID- 16562356
TI  - Ethical issues and public opinion.

PMID- 16562357
TI  - Using clinical evidence to manage pharmacy benefits: experiences of six states.
AB  - Medicaid agencies report that pharmacy costs are a major driver of overall
      program spending growth. Many states believe that clinical evidence can be used
      to curtail pharmacy costs while ensuring beneficiary access to needed
      prescription drugs. In 2004, researchers from the National Academy for State
      Health Policy and Georgetown University conducted site visits to examine how
      state Medicaid agencies in California, Florida, Kansas, Michigan, Missouri, and
      Washington manage their pharmacy benefits. This brief focuses on states' use of
      clinical evidence and preferred drug lists. It summarizes the states' experiences
      in four areas of pharmacy benefit management: the role of pharmaceutical and
      therapeutics committees in developing preferred drug lists; use of prior approval
      processes to enforce preferred drug lists; the role played by the Drug
      Effectiveness Review Project in helping states manage drug utilization; and the
      management of behavioral health pharmaceuticals.

PMID- 16562359
TI  - Image of the month. Cholesterol embolization.

PMID- 16562360
TI  - Fragile X syndrome.

PMID- 16562361
TI  - Antiretroviral treatment of HIV infection: Swedish recommendations 2005.
AB  - On 2 earlier occasions, in 2002 and 2003, the Swedish Medical Products Agency
      (MPA) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly
      publicized recommendations for the treatment of HIV infection. A working group
      from the same expert team that produced the 2002 report has now revised the text
      again. Since the publication of the last treatment recommendations, 4 new
      medicines have become available: emtricitabine, atazanavir, fosamprenavir, and
      enfuvirtid. The last-mentioned belongs to a new class of HIV medications called
      fusion inhibitors (Box 1). It is likely that tipranavir will also be on the
      market soon. Simultaneously, the drug zalcitabin has been deregistered. The
      following updated recommendations parallel the earlier ones, but increased
      knowledge allows us to be more specific in our recommendations. Thus, it is now
      suggested that the initial treatment for HIV infection consist of 2 nucleoside
      reverse transcriptase inhibitors (NRTIs) and 1 non-nucleoside reverse
      transcriptase inhibitor (NNRTI); or 2 NRTIs and 1 protease inhibitor (PI). In the
      group of the NRTIs, stavudine is no longer recommended for this purpose. In the
      NNRTI group, efavirenz should be preferred to nevirapine, except under special
      circumstances. Finally, PIs ought to be boosted with ritonavir (PI/r). Also new
      are recommendations regarding treatment choices for patients co-infected with
      hepatitis B virus (HBV) or tuberculosis (TB). As in the case of the previous
      publication, recommendations are evidence-graded in accordance with the Oxford
      Centre for Evidence Based Medicine, 2001 (see
      http://www.cebm.net/levels_of_evidence.asp#levels), and have been supplemented
      with references to newly-added sections and data not referred to in earlier
      background documentation.

PMID- 16562362
TI  - Relationship between physiological profiles and on-ice performance of a National
      Collegiate Athletic Association Division I hockey team.
AB  - Ice hockey is a game that relies heavily on both aerobic and anaerobic energy
      production systems as players perform in various game situations. However, we
      found no studies evaluating the relationship between a player's physical
      condition and individual success in games throughout a competitive hockey season.
      The purpose of this study was to determine the relationship between a player's
      aerobic fitness (VO(2)max), blood lactate, and percent body fat to his total
      minutes played during a season (Tmin) and net scoring chances (SCn). Players' (N
      = 29) preseason VO(2)max, lactate at the fourth stage of an incremental treadmill
      test (Lac 4), and percent body fat values from the 1999- 2001 National Collegiate
      Athletic Association Division I hockey seasons were archived and retrieved for
      this study. The players' Tmin and SCn were used as the on-ice performance
      variables and were compared with their fitness measures. Lactate at 4th treadmill
      stage (r = 0.41, p < 0.03) and percent body fat (r = 0.39, p < 0.03) but not
      VO(2)max (r = 0.20, p < 0.24) were significantly related to Tmin. Both Lac 4 and
      percent body fat were entered into a stepwise regression model that accounted for
      25% of the variance in Tmin among players (p < 0.02). Both VO(2)max (r = 0.41, p
      < 0.03) and Lac 4 (r = 0.33, p < 0.05) were significantly related to the players'
      SCn, but percent body fat was not (r = 0.10, p < 0.57). Only VO(2)max
      significantly predicted the players' SCn, accounting for 17% of the variance.
      These findings suggest a relationship between a player's conditioning level and
      on-ice performance. Our results support the value of implementing seasonal
      physiological testing, which will help strength and conditioning coaches make
      individualized modifications to a player's fitness regimens in an effort to
      improve specific physiological attributes.

PMID- 16562363
TI  - Current awareness on yeast.

PMID- 16562364
TI  - Investigating healthcare providers' knowledge of trichotillomania and its
      treatment.
AB  - Given the low prevalence rate and rather secretive nature of trichotillomania, it
      is uncertain how much trichotillomania-related knowledge physicians and
      psychologists possess, what the perceived role of a psychologist is in the
      treatment process, what level of familiarity practitioners have with effective
      treatments and whether providers have resource materials available for patients.
      In a postal survey of 501 psychologists and physicians in the USA, providers
      responded correctly to 61% of the general knowledge items about trichotillomania.
      Most providers believed that psychologists may play a variety of roles in the
      clinical management of the disorder. Although providers were fairly accurate
      about the effectiveness of certain treatments for trichotillomania (e.g.
      medication, habit-reversal), a number of non-empirically supported treatments
      were endorsed as being effective. Furthermore, an overwhelming majority of
      healthcare providers did not have resources or referral information available for
      patients with trichotillomania. Implications of the findings and limitations of
      the study are discussed.

PMID- 16562365
TI  - Cancer-related anemia.

PMID- 16562366
TI  - Recent advances in the treatment of transplant-related lymphoma.

PMID- 16562367
TI  - Current insights on the risk of thrombogenicity with off-label use of rFVlla.

PMID- 16562368
TI  - Use of dose-dense chemotherapy in the management of breast cancer.

PMID- 16562369
TI  - mTOR inhibitors.

PMID- 16562370
TI  - Updates and controversies in the treatment of pancreatic cancer.
AB  - Despite the many advances in oncology over the last few decades, almost all
      patients with pancreatic cancer eventually die of the disease. Recent advances,
      however, have led to the development of more effective therapies. In pancreatic
      cancer, as in many other malignancies, significant progress in the understanding
      of important molecular processes associated with the development and progression
      of the disease is helping tailor more effective treatment strategies. Molecularly
      targeted agents are offering hope for their potential role in helping translate
      the improved activity of combination chemotherapy into improved survival. This
      article summarizes the data from studies that established standards of care and
      others that created controversy, and reviews novel treatment strategies for this
      intractable disease.

PMID- 16562371
TI  - Treatment of acute promyelocytic leukemia with gemtuzumab ozogamicin.
AB  - Acute promyelocytic leukemia (APL) is a form of acute myeloid leukemia
      characterized by peculiar biologic features and a unique sensitivity to
      differentiation therapy with all-trans retinoic acid (ATRA). Modern treatment
      approaches to APL include simultaneous combination of ATRA and anthracycline
      based chemotherapy. Gemtuzumab ozogamicin is a calicheamicin-conjugated
      monoclonal antibody directed against CD33, a cell surface antigen highly
      expressed on APL cells. Engagement of CD33 by gemtuzumab results in
      immunoconjugate internalization and hydrolytic release of calicheamicin, which,
      in turn, causes irreversible DNA damage and cell death. A number of preliminary
      reports have highlighted the sensitivity of APL to gemtuzumab given alone or in
      combination with other agents. Several reasons may account for the efficacy of
      gemtuzumab in APL, including: (1) CD33 is detectable in virtually 100% of APL
      cases; (2) calicheamicin belongs to the anthracycline family, a group of
      chemotherapeutic agents known to be highly effective in APL; and (3) the APL
      blast cells lack the multidrug resistance glycoprotein 170. Due to the
      availability of other highly effective agents (ATRA, arsenic trioxide),
      relatively few APL patients have been treated thus far with gemtuzumab, and their
      follow-up is still short. However, it is conceivable that the use of this agent
      in APL will increase in the near future in light of its capability to induce
      molecular remission even in advanced disease. Furthermore, the use of low doses
      of gemtuzumab in high-risk patients might be relevant in order to reduce
      treatment toxicity due to conventional anthracyclines. This review summarizes the
      mechanism of action and toxicity profile of gemtuzumab as well as the published
      experience with this compound in patients with newly diagnosed and relapsed APL.

PMID- 16562372
TI  - Overview of anti-VEGF therapy and angiogenesis. Part 1: Angiogenesis inhibition
      in solid tumor malignancies.
AB  - Several new agents that target the vascular endothelial growth factor (VEGF)
      pathway and inhibit angiogenesis are emerging as promising therapies in multiple
      cancer types. Bevacizumab, a humanized monoclonal antibody to VEGF-A, is
      currently approved in combination with intravenous 5-fluorouracil-containing
      regimens for the first-line treatment of metastatic colorectal cancer and
      recently demonstrated clinically important results in combination with
      chemotherapy in patients with non-small cell lung cancer and metastatic breast
      cancer. Other anti-VEGF agents that have shown benefit in various cancer types
      will be discussed in this monograph. Despite the often striking results observed
      with anti-VEGF agents, several unanswered questions remain, such as the optimal
      duration of therapy and patient selection criteria. These other issues, including
      the biologic rationale for anti-VEGF therapy, as well as recent clinical trial
      data with anti-VEGF agents in colorectal, pancreatic, lung, kidney, and brease
      cancers, are discussed.

PMID- 16562373
TI  - ABCG2 (BCRP): a cytoprotectant in normal and malignant stem cells.
AB  - ABCG2 is a member of the adenosine triphosphate-binding cassette (ABC) family of
      cell surface transport proteins. ABCG2 is expressed in many types of primitive
      repopulating cells, and may be a marker of tumor stem cells. The physiologic role
      of ABCG2 seems to be excretion of genotoxic substances from the body and from
      primitive repopulating cell populations. A unifying hypothesis is presented,
      linking the expression of ABCG2 in normal and malignant stem cells with a
      physiologic role for protection of stem cells. Future studies will explore the
      possible role of ABCG2 in tumor stem cells and how this may influence the
      selection of new cancer therapeutic strategies.

PMID- 16562374
TI  - Therapeutic management of a patient with a unique factor IX sensitivity to
      warfarin.

PMID- 16562375
TI  - Seasonal microbial ribotype shifts in the sulfurous karstic lakes Ciso and Vilar,
      in northeastern Spain.
AB  - Spatio-temporal changes in two sulfurous lakes from the karstic area of Banyoles
      (Girona, Spain), holomictic lake Ciso and meromictic lake Vilar, were studied
      over one year. Samples were collected at different depths from the two lakes on
      the same days, during each of the four seasons, and several physico-chemical
      variables (temperature, light, pH, conductivity, sulfide, oxygen concentration,
      pigment concentrations, etc.) were measured. To fingerprint bacterial populations
      from each sample, DNA was extracted, bacterial 16S rRNA genes were amplified by
      PCR, and restriction fragment length polymorphism (RFLP) analyses of the total
      bacterial 16S rDNAs were performed. Each 16S rDNA pool was independently digested
      with three restriction endonucleases (AluI, HinfI, and RsaI) and separated
      electrophoretically. More restriction fragments were obtained from the Lake Vilar
      samples than from the Lake Ciso samples. Moreover, intrasample and intersample
      differences were observed in each lake. RFLP patterns were compared by scoring
      similarities using the Jaccard coefficient and then building a multidimensional
      scaling (MDS) map from the resulting similarities matrix. In both lakes, results
      indicated that seasonality was mostly responsible for the observed fluctuations
      in the RFLP patterns, while the effect of stratification was less pronounced.

PMID- 16562376
TI  - Statistical optimization of a culture medium for biomass and poly(3
      hydroxybutyrate) production by a recombinant Escherichia coli strain using
      agroindustrial byproducts.
AB  - A statistically based Plackett-Burman screening design identified milk whey and
      corn steep liquor concentrations as well as ionic strength (based on phosphate
      buffer concentration) as the three main independent components of the culture
      medium that significantly (p < 0.05) influenced biomass and poly(3
      hydroxybutyrate) (PHB) production in recombinant cells of Escherichia coli. This
      strain carries a plasmid encoding phb genes from a natural isolate of Azotobacter
      sp. Response surface methodology, using a central composite rotatable design,
      demonstrated that the optimal concentrations of the three components, defined as
      those yielding maximal biomass and PHB production in shaken flasks, were 37.96 g
      deproteinated milk whey powder/l, 29.39 g corn steep liquor/l, and 23.76 g
      phosphates/l (r2 = 0.957). The model was validated by culturing the recombinant
      cells in medium containing these optimal concentrations, which yielded 9.41 g
      biomass/l and 6.12 g PHB/l in the culture broth. Similar amounts of PHB were
      obtained following batch fermentations in a bioreactor. These results show that
      PHB can be produced efficiently by culturing the recombinant strain in medium
      containing cheap carbon and nitrogen sources.

PMID- 16562377
TI  - Widespread occurrence of non-phosphorylating glyceraldehyde-3-phosphate
      dehydrogenase among gram-positive bacteria.
AB  - The non-phosphorylating glyceraldehyde 3-phosphate dehydrogenase (GAPDHN, NADP+
      specific, EC 1.2.1.9) is present in green eukaryotes and some Streptococcus
      strains. The present report describes the results of activity and immunoblot
      analyses, which were used to generate the first survey of bacterial GAPDHN
      distribution in a number of Bacillus, Streptococcus and Clostridium strains.
      Putative gapN genes were identified after PCR amplification of partial 700-bp
      sequences using degenerate primers constructed from highly conserved protein
      regions. Alignment of the amino acid sequences of these fragments with those of
      known sequences from other eukaryotic and prokaryotic GAPDHNs, demonstrated the
      presence of conserved residues involved in catalytic activity that are not
      conserved in aldehyde dehydrogenases, a protein family closely linked to GAPDHNs.
      The results confirm that the basic structural features of the members of the
      GAPDHN family have been conserved throughout evolution and that no identity
      exists with phosphorylating GAPDHs. Furthermore, phylogenetic trees generated
      from multiple sequence alignments suggested a close relationship between plant
      and bacterial GAPDHN families.

PMID- 16562378
TI  - Phenotypic, genotypic, and phylogenetic discrepancies to differentiate Aeromonas
      salmonicida from Aeromonas bestiarum.
AB  - The taxonomy of the "Aeromonas hydrophila" complex (comprising the species A.
      hydrophila, A. bestiarum, A. salmonicida, and A. popoffii) has been
      controversial, particularly the relationship between the two relevant fish
      pathogens A. salmonicida and A. bestiarum. In fact, none of the biochemical tests
      evaluated in the present study were able to separate these two species. One
      hundred and sixteen strains belonging to the four species of this complex were
      identified by 16S rDNA restriction fragment length polymorphism (RFLP).
      Sequencing of the 16S rDNA and cluster analysis of the 16S-23S intergenic spacer
      region (ISR)-RFLP in selected strains of A. salmonicida and A. bestiarum
      indicated that the two species may share extremely conserved ribosomal operons
      and demonstrated that, due to an extremely high degree of sequence conservation,
      16S rDNA cannot be used to differentiate these two closely related species.
      Moreover, DNA-DNA hybridization similarity between the type strains of A.
      salmonicida subsp. salmonicida and A. bestiarum was 75.6 %, suggesting that they
      may represent a single taxon. However, a clear phylogenetic divergence between A.
      salmonicida and A. bestiarum was ascertained from an analysis based on gyrB and
      rpoD gene sequences, which provided evidence of a lack of congruence of the
      results obtained from 16S rDNA, 16S-23S ISR-RFLP, DNA-DNA pairing, and
      biochemical profiles.

PMID- 16562379
TI  - Genomic divergence of Escherichia coli strains: evidence for horizontal transfer
      and variation in mutation rates.
AB  - This report describes the sequencing in the Escherichia coli B genome of 36
      randomly chosen regions that are present in most or all of the fully sequenced E.
      coli genomes. The phylogenetic relationships among E. coli strains were examined,
      and evidence for the horizontal gene transfer and variation in mutation rates was
      determined. The overall phylogenetic tree indicated that E. coli B and K-12 are
      the most closely related strains, with E. coli O157:H7 being more distantly
      related, Shigella flexneri 2a even more, and E. coli CFT073 the most distant
      strain. Within the B, K-12, and O157:H7 clusters, several regions supported
      alternative topologies. While horizontal transfer may explain these phylogenetic
      incongruities, faster evolution at synonymous sites along the O157:H7 lineage was
      also identified. Further interpretation of these results is confounded by an
      association among genes showing more rapid evolution and results supporting
      horizontal transfer. Using genes supporting the B and K-12 clusters, an estimate
      of the genomic mutation rate from a long-term experiment with E. coli B, and an
      estimate of 200 generations per year, it was estimated that B and K-12 diverged
      several hundred thousand years ago, while O157:H7 split off from their common
      ancestor about 1.5-2 million years ago.

PMID- 16562380
TI  - Regulation of conjugal transfer by Lrp and Dam methylation in plasmid R100.
AB  - Conjugal transfer of the F-like plasmid R100 occurs at higher frequencies in the
      absence of DNA adenine methylation. Lower levels of R100-encoded FinP RNA were
      found in a Dam host, suggesting that Dam methylation regulates FinP RNA
      synthesis. Lack of the leucine-responsive regulatory protein (Lrp) causes a
      decrease in R100 plasmid transfer, indicating that Lrp is an activator of R100
      mediated conjugation. Hence, host-encoded regulators previously described for the
      Salmonella virulence plasmid (pSLT) seem to play analogous roles in R100.
      Repression of conjugal transfer in rich medium is an additional trait shared by
      R100 and pSLT. DNA sequence comparisons in regulatory loci support the view that
      R100 and pSLT are closely related.

PMID- 16562381
TI  - Molecular characterization of InJR06, a class 1 integron located in a conjugative
      plasmid of Salmonella enterica ser. Typhimurium.
AB  - The presence of class 1, 2, and 3 integrons was investigated in four pediatric
      isolates of Salmonella enterica ser. Typhimurium (S. Typhimurium). A class 1
      integron was detected in one S. Typhimurium strain, the only one that also showed
      resistance to various aminoglycoside antibiotics. This integron, called InJR06,
      and the aminoglycoside resistance determinants were located in pS06, a large (>
      or = 55 kb) conjugative plasmid. A single mobile cassette (encoding the
      aminoglycoside adenylyltransferase ANT(3'')-Ia) was detected in the variable
      region of InJR06, while the architecture of the attI1 and attC sites was
      conserved.

PMID- 16562382
TI  - Measuring hot flashes in men treated with hormone ablation therapy: an unmet
      need.

PMID- 16562383
TI  - Acupuncture for urinary urgency in women over 50: what is the evidence?

PMID- 16562384
TI  - Urinary drainage following continence surgery: development of Canadian best
      practice guidelines.
AB  - INTRODUCTION: Researchers evaluated the impact of a new algorithm for
      postoperative catheter removal with women who underwent surgery for stress
      incontinence. OBJECTIVE: This study aimed to improve the postoperative process by
      developing practice guidelines for urinary drainage after surgery for urinary
      stress incontinence in a female population. METHOD: The quality improvement study
      collected 2 years of retrospective data and 1 year of prospective data on all
      women who had surgery for stress incontinence. This involved a variety of
      surgical procedures that were performed by a small number of surgeons. RESULTS:
      Burch colposuspension was the predominant procedure, and on the prospective piece
      of the study, with the new guidelines, time to first postoperative void
      decreased. CONCLUSIONS: Fewer interventions and decreased length of stay
      indicated that the guidelines are evidence of improved practice.

PMID- 16562385
TI  - Factors impacting self-care for urinary incontinence.
AB  - INTRODUCTION: Behavioral strategies such as pelvic floor muscle exercises (PFME),
      bladder retraining, and dietary modifications are generally considered to be the
      first line of treatment for urinary incontinence (UI). Yet little is understood
      about the client's abilities/motivation to manage their UI in the home setting.
      Self-care, the ability of clients to act on their own behalf to achieve and
      maintain health, is a fundamental component of these strategies. Despite the
      frequently chronic nature of UI, there is growing evidence that such maintenance
      of behavioral therapies is sporadic at best. OBJECTIVE: The purpose of this study
      was to enhance understanding of self-care strategies that individuals with UI
      employ, the perceived benefits of these strategies, the factors that influence
      their self-care choices, and the factors that impede or facilitate maintenance of
      behavioral therapies. METHOD: In this qualitative descriptive study, individual
      and focus group interviews with community-dwelling participants were conducted to
      enhance understanding regarding the participants' management of UI at home and
      why they maintain certain strategies and not others. Data were collected via
      loosely constructed individual (n=25) and focus group (n=3) interviews to
      facilitate open discussion of participants' perceptions. RESULTS: Thirty-eight
      individuals (33 women and 5 men) participated in the study. Analysis of data
      resulted in a major category of self-care strategies related to UI that was
      further subcategorized into factors that facilitated PFME and barriers to PFME
      performance. Factors that facilitated PFME included: (a) realistic goals and
      expectation, (b) positive affirmation, (c) follow up, and (d) maintaining an
      exercise routine. Barriers noted were: (a) insufficient information, (b)
      characteristics of the exercises, (c) competing interests, (d) financial cost,
      and (e) minor psychosocial impact. CONCLUSIONS: This study described the self
      care strategies that participants with UI had initiated and maintained and
      additionally explored the perceived facilitators and barriers to self-care
      choices. Two major themes emerged: (a) self-care efforts were motivated by desire
      for a normal daily lifestyle and (b) participants were motivated to maintain
      strategies by the ability to visualize progress and by knowledge that they were
      progressing. These findings support the need for client-focused teaching that is
      grounded in the individual's daily realities and goals.

PMID- 16562386
TI  - Urinary incontinence occurring during intercourse: effect on sexual function in
      women.

PMID- 16562387
TI  - Prostate HDR radiation therapy: a comparative study evaluating the effectiveness
      of pain management with peripheral PCA vs. PCEA.
AB  - INTRODUCTION: High dose rate (HDR) brachytherapy is considered one of the most
      advanced treatment technologies currently available for treatment of localized
      prostate cancer. It gives the advantage of applying higher dose radiation, with
      greater precision, directly to the tumor while sparing healthy tissue and
      surrounding organs, thereby resulting in fewer side effects. In this facility,
      the treatment requires an overnight stay in the hospital, in a supine position,
      with a perineal template sutured to the perineum to prevent catheter movement or
      dislodgement. PURPOSE: To compare the effectiveness of pain management for men
      with prostate cancer being treated with HDR brachytherapy using a peripheral
      patient controlled analgesia (PCA) or patient controlled epidural analgesia
      (PCEA). METHOD: A comparative study was conducted evaluating the effectiveness of
      two pain management methods for men with prostate cancer receiving HDR
      brachytherapy. Pain assesments were conducted by scoring pain from the Foley
      catheter, interstitial catheter (perineal) and back (lumbosacral), using the
      Brief Pain Inventory Scale. RESULTS: Patients receiving pain management with the
      PCEA experienced significantly less pain. CONCLUSIONS: These finding suggest that
      use of PCEA with bupivacaine and fentanyl is more effective in managing pain
      related to HDR brachytherapy for prostate cancer, and results in a positive
      patient outcome thereby improving patient satisfaction.

PMID- 16562388
TI  - EBP: pain control for prostate cancer patients receiving HDR brachytherapy.

PMID- 16562389
TI  - Update on avian influenza pandemic threat.
AB  - So far, the current risk to people in the United States from the H5N1 bird flu
      outbreak in Asia is low (CDC, 2005a). The strain of H5N1 virus found in Asia has
      not been found in the United States; and as of November 2005, there have been no
      human cases of H5N1 flu reported in the United States. Travel to countries in
      Asia has not been restricted, but travelers are advised to avoid all direct
      contact with poultry, poultry farms, animals in live food markets, and any
      surfaces that appear to be contaminated with feces from poultry or other animals
      (CDC, 2005a). Meanwhile, medical and public health personnel are watching closely
      and preparedness plans are under way to respond to the threat of an avian
      influenza pandemic.

PMID- 16562390
TI  - Getting ready for certification: testes cancer.

PMID- 16562391
TI  - Delayed presentation of posterior urethral valves in a child with autism.

PMID- 16562392
TI  - Tegress: a new approach to urethral implants.

PMID- 16562393
TI  - Care of the patient with an indwelling catheter.

PMID- 16562395
TI  - Taking the leap...

PMID- 16562396
TI  - Does secondary smoke exposure increase the incidence and/or severity of asthma in
      children?
AB  - Pediatric asthma is a significant health problem in the United States. Up to
      26,000 new asthma cases are identified every year. Seventeen percent of all
      pediatric emergency department visits are attributable to asthma. There are no
      universally agreed upon diagnostic criteria for asthma. Because no single agent
      has been identified as causing asthma and because no pathologic feature is
      entirely unique to asthma, the disease can more easily be described than defined.
      Asthma is diagnosed clinically based upon recurrent episodes of wheezing,
      breathlessness, chest tightness and coughing, particularly at night in the
      absence of other causes. Asthma is considered a chronic inflammatory disorder
      associated with airflow obstruction, which is often reversible either
      spontaneously or with treatment. This inflammation exacerbates bronchial hyper
      responsiveness to a variety of environmental stimuli including allergens and
      irritants. Due to inconsistency of diagnostic criteria for asthma, it is easier
      to measure asthma severity or to study events such as hospitalizations or deaths,
      rather than to measure incidence. Since a randomized controlled trial of the
      effect of cigarette exposure on asthma would be unethical, we must rely on either
      randomized trials of reduction of cigarette exposure or epidemiological studies
      to determine associations between secondary exposure to cigarette smoke and
      asthma.

PMID- 16562397
TI  - Perform a gene test on every patient: the medical family history revisited.
AB  - The medical family history is the most practical personalized genomic tool, yet
      healthcare professionals often undervalue and underutilize it. Collecting and
      interpreting the medical family history is an important task for all clinicians.
      It can shed light on the complex interactions of genetic, environmental, and
      behavioral factors that determine a patient's present problem and can also
      indicate a patient's risk for common chronic conditions. Physicians can use a
      medical family history to diagnose disease, optimize therapy, plan screening, and
      avoid disease. The medical family history is dynamic so it must be updated
      regularly. Referral to a genetic specialist needs to be made when a moderate to
      high risk is identified or there is need for specific gene testing. A
      reproducible template is provided to expedite family history collection and
      interpretation.

PMID- 16562398
TI  - Senior health and low vision.

PMID- 16562399
TI  - Outsourcing the revenue cycle.

PMID- 16562400
TI  - First year of medical school.

PMID- 16562401
TI  - Marital status, alcohol dependence, and GABRA2: evidence for gene-environment
      correlation and interaction.
AB  - OBJECTIVE: The gene GABRA2 has been associated with the risk for alcohol
      dependence in independent samples. This article explores how this genetic risk
      factor interacts with marital status, another factor previously shown to be
      associated with the risk for alcohol dependence. METHOD: Data from more than
      1,900 male and female subjects from the Collaborative Study of the Genetics of
      Alcoholism (COGA) sample were analyzed. Subjects were recruited based on
      membership in a family with multiple individuals with alcoholism. A series of
      analyses was performed to evaluate the relationship between the following: (1)
      GABRA2 and alcohol dependence, (2) marital status and alcohol dependence, (3)
      GABRA2 and marital status, and (4) interactions between GABRA2 and marital status
      on the development of alcohol dependence in the high-risk COGA sample. Additional
      analyses were carried out in a sample of approximately 900 individuals from
      control families to test the generalizability of results. RESULTS: Both GABRA2
      and marital status contributed independently to the development of alcohol
      dependence in the COGA sample. The high-risk genotype at GABRA2 was also related
      to a decreased likelihood of marrying and an increased likelihood of divorce,
      which appeared to be mediated in part by personality characteristics. There was
      also differential risk associated with the GABRA2 genotype according to marital
      status. CONCLUSIONS: These analyses provide evidence of both gene-environment
      correlation and gene-environment interaction associated with GABRA2, marital
      status, and alcohol dependence. They illustrate the complex pathways by which
      genotype and environmental risk factors act and interact to influence alcohol
      dependence and challenge traditional conceptualizations of "environmental" risk
      factors.

PMID- 16562402
TI  - High- and low-dose expectancies as mediators of personality dimensions and
      alcohol involvement.
AB  - OBJECTIVE: The present study examined the influences of personality dimensions
      (extraversion, neuroticism) on college alcohol involvement both (1) directly and
      (2) mediated by positive and negative alcohol expectancies across two imagined
      (high and low) alcohol doses. METHOD: Participants (N = 339; 176 women) were
      regularly drinking college students who completed a questionnaire battery on
      demographic characteristics, personality, expectancies, and alcohol use and
      problems. RESULTS: Structural equation modeling analysis of low- and high-dose
      models revealed partial support for the Social Learning Theory conceptualization
      of expectancies as mediators of more distal (personality) influences.
      Interestingly, patterns of association differed by dose. At high-expectancy
      doses, positive alcohol expectancies fully mediated the extraversion-use
      association. At low doses, positive expectancies did not play a critical role.
      Two distinct pathways from neuroticism to alcohol use were observed: a direct
      pathway, whereby neuroticism is a protective factor for alcohol use, and an
      indirect pathway, through positive expectancies, whereby neuroticism is a risk
      factor. The protective pathway was evident regardless of expectancy doses,
      whereas the risk pathway was evident only at high doses. Negative expectancies
      partially mediated the association between neuroticism and alcohol problems at
      both high- and low-expectancy doses. CONCLUSIONS: These data underscore the
      unique role of both positive and negative expectancies in the association between
      personality and drinking behavior and point to the importance of considering
      alcohol dose when assessing expectancies. Findings suggest that it may be beliefs
      about the effects resulting from heavy (rather than moderate) drinking that may
      be the active mechanism underlying drinking behavior.

PMID- 16562403
TI  - An evaluation of the level of response to alcohol, externalizing symptoms, and
      depressive symptoms as predictors of alcoholism.
AB  - OBJECTIVE: The development of alcohol-use disorders (AUDs) reflects a complex
      relationship between genetic influences and environmental/cultural forces. Some
      genes operate through intermediate phenotypes, including a low level of response
      (LR) to alcohol, externalizing symptoms (EXT), and internalizing characteristics
      such as depressive syndromes (DEP). This article evaluates the impact of these
      three intermediate phenotypes and additional domains in a structural equation
      model (SEM). METHOD: Data were available from baseline at approximately age 20
      for LR, as well as from additional domains at the 10- and 15-year follow-up
      periods for 393 men from the San Diego Prospective Study. Correlational analyses
      and an AMOS-based SEM were used to evaluate the development of alcohol problems,
      including AUDs, with the hypothetical model based on results from prior studies
      evaluating each key intermediate phenotype separately. RESULTS: The SEM explained
      51% of the variance of the 15-year outcome, and had good fit characteristics. The
      family history ofAUDs (FHalc) was linked, directly or indirectly, to all three
      key domains. The combination of LR and EXT mediated the relationship between
      FHalc and 15-year alcohol outcomes, with a trend (p = .07) for LR to mediate
      between FHalc and the 10-year outcome. DEP, by itself, did not mediate FHalc to
      alcoholism. The LR predicted the 15-year outcome both through alcohol problems at
      10 years and via drinking to cope (COPE), with each of these domains functioning
      as mediators. The relationship of EXT to outcome was mediated by alcohol
      expectations (EXPECT) and by COPE. DEP added to the model in the context of an FH
      of independent depressions, stress, and lower social supports, subsequently
      affecting COPE. CONCLUSIONS: The results indicate that the development of AUDs
      reflects several genetically influenced endophenotypes in the context of multiple
      additional domains. Both EXPECT and COPE represented important pathways through
      which the phenotypes influenced the AUD risk.

PMID- 16562404
TI  - Opioid substitution treatment reduces substance use equivalently in patients with
      and without posttraumatic stress disorder.
AB  - OBJECTIVE: The purpose of this study was to determine whether opioid-dependent
      patients with diagnosed posttraumatic stress disorder (PTSD) have poorer long
      term outcomes in opioid substitution treatment than do patients without PTSD.
      METHOD: This prospective observational study examined outcomes of 255 opioid
      dependent patients (men = 248) entering opioid substitution treatment at eight
      clinics in the Veterans Health Administration (VHA). Subjects were interviewed at
      treatment entry, 6 months, and 1 year about substance use and related problems,
      health status, treatment satisfaction, and non-VHA health care utilization.
      Medical records were reviewed to obtain toxicology results, health care
      utilization data, and diagnoses. Medical record review identified a diagnosis of
      PTSD in 71 (28%) patients. Substance-use and mental-health outcomes and health
      care utilization in the first year following treatment entry were compared
      between patients with and without a diagnosis of PTSD. RESULTS: Patients with and
      without PTSD had similar treatment responses. Although patients with PTSD had
      longer histories of drug use at intake, at 1-year follow-up they showed
      reductions in heroin, cocaine, and alcohol use, comparable to patients without
      the disorder. PTSD patients received higher doses of opiate medication, attended
      more psychosocial treatment sessions for substance-use disorder, and had better
      treatment retention. Psychiatric symptoms for patients with PTSD were more severe
      at intake and showed little improvement throughout treatment. CONCLUSIONS: Opioid
      substitution therapy is as effective at reducing substance use in PTSD patients
      as it is in patients without the disorder, but additional services are needed for
      treatment of psychological problems that are largely unchanged by treatment for
      addiction.

PMID- 16562405
TI  - Traditional practices, traditional spirituality, and alcohol cessation among
      American Indians.
AB  - OBJECTIVE: The detrimental effects of alcohol misuse and dependence are well
      documented as an important public-health issue among American Indian adults. This
      preponderance of problem-centered research, however, has eclipsed some important
      resilience factors associated with life course patterns of American Indian
      alcohol use. In this study, we investigate the influence of enculturation, and
      each of the three component dimensions (traditional practices, traditional
      spirituality, and cultural identity) to provide a stringent evaluation of the
      specific mechanisms through which traditional culture affects alcohol cessation
      among American Indians. METHOD: These data were collected as part of a 3-year
      lagged sequential study currently underway on four American Indian reservations
      in the upper Midwest and five Canadian First Nation reserves. The sample
      consisted of 980 Native American adults, with 71% women and 29% men who are
      parents or guardians of youth ages 10-12 years old. Logistic regression was used
      to assess the unique contribution of the indicators of alcohol cessation.
      Excluding adults who had no lifetime alcohol use, the total sample size for
      present analysis is 732 adult respondents. RESULTS: The findings show that older
      adults, women, and married adults were more likely to have quit using alcohol.
      When we examined the individual components of enculturation, two of the three
      components (participation in traditional activities and traditional spirituality)
      had significantly positive effects on alcohol cessation. CONCLUSIONS: Although
      our findings provide empirical evidence that traditional practices and
      traditional spirituality play an important role in alcohol cessation, the data
      are cross-sectional and therefore do not indicate direction of effects.
      Longitudinal studies are warranted, in light of the work that concludes that
      cultural/spiritual issues may be more important in maintaining sobriety once it
      is established rather than initiating it.

PMID- 16562406
TI  - Alcohol use by pregnant women: partners, knowledge, and other predictors.
AB  - OBJECTIVE: The impact of a couple's knowledge about healthy pregnancy habits
      involving alcohol and substance use was assessed in the context of other factors
      previously identified to predict prenatal alcohol consumption in a sample of 254
      pregnant women and their male partners. METHOD: Couples were asked to assess
      independently a series of statements (true or false) describing the consequences
      of prenatal substance exposure, while also providing information about their own
      drinking. RESULTS: Although the couples demonstrated good knowledge of healthy
      habits during pregnancy, they did not agree when the element of chance was
      considered. Median household income was more highly predictive of a pregnant
      woman's knowledge score than her partner's score. In turn, the subject's
      knowledge of healthy pregnancy habits as manifested in the assessment score had
      only a weak relationship with prenatal alcohol consumption. Previous alcohol use
      by the pregnant woman was the strongest predictor of prenatal alcohol use.
      CONCLUSIONS: Because previous alcohol consumption use by the pregnant woman was
      the strongest predictor of prenatal alcohol use, the importance of its accurate
      identification is emphasized. Although pending further investigation, knowledge
      about healthy pregnancy behaviors may exert greater impact if it is shared by a
      pregnant woman and her partner.

PMID- 16562407
TI  - Gender differences among young drivers in the association between high-risk
      driving and substance use/environmental influences.
AB  - OBJECTIVE: The primary aim of this article is to assess young drivers' gender
      differences in the associations between substance use/environmental influences
      and high-risk driving behavior. METHOD: We determine the association of 12th
      grade self-reported substance use/ environmental influences with high-risk
      driving behavior as quantified by the number of offenses, serious offenses,
      crashes, and single-vehicle crashes on state driving records during subjects' (N
      = 3,607; 51% male) first 4 years of licensure. RESULTS: The associations between
      high-risk driving and substance use/environmental influences were generally
      stronger among women than among men. When matched by substance-use profiles,
      women had fewer risky-driving incidents than men. CONCLUSIONS: The results
      indicate that young women who exhibit high-risk driving behavior deviate more
      from the general population of young women with respect to alcohol use, alcohol
      misuse, and marijuana use than high-risk-driving young men differ from other
      young men. In addition, findings indicate that even if young men and women were
      to eventually have equal levels of substance use, women would likely retain their
      lower-risk driving profiles. These findings suggest the need for (1) future
      research to understand the differential associations, and (2) prevention programs
      that consider these gender differences.

PMID- 16562408
TI  - The efficacy of experimental interventions designed to reduce drinking among
      designated drivers.
AB  - OBJECTIVE: Designated drivers are a popular strategy for avoiding drunk driving.
      However, studies have demonstrated that the strategy is often implemented poorly,
      resulting in diminished risk-reduction effectiveness. The purpose of this study
      was to test the efficacy of six interventions designed to reduce alcohol
      consumption among designated drivers. METHOD: A total of 376 groups consisting of
      1,412 pedestrians (57.8% men) were recruited as they crossed into Tijuana,
      Mexico, from San Diego, CA. Before crossing into Mexico, each group was assigned
      at random to one of six experimental conditions or to one control condition. The
      six interventions were designed to (1) cue the use of designated drivers, (2)
      change attitudes about designated drivers, (3) provide monetary rewards for
      driver sobriety, and (4) increase group supportive norms for proper designated
      driver use. Participant breath alcohol concentrations (BrACs) were collected
      before entering Mexico and on return to the United States. RESULTS: Using group
      members to deliver pro-designated driver messages significantly decreased driver
      and passenger BrACs relative to controls. Male drivers were more likely to return
      from Mexico with BrACs of zero if they were rewarded. Among female drivers,
      wearing a bracelet with the printed words "designated driver" in addition to
      cuing resulted in 9 of 10 drivers returning with BrACs equal to zero.
      CONCLUSIONS: These results demonstrate that designated driver sobriety can be
      enhanced through brief interventions, and proper use of the designated driver
      concept did not increase the risk of excessive alcohol consumption for
      passengers.

PMID- 16562409
TI  - Do we learn from our mistakes? An examination of the impact of negative alcohol
      related consequences on college students' drinking patterns and perceptions.
AB  - OBJECTIVE: Little research has examined antecedents of specific drinking
      consequences (vomiting, regretted sex, hangover, blackouts) among college
      students. This research examined how students' experiences of past consequences
      relate to their beliefs of experiencing similar consequences in the future and
      how these beliefs relate to current drinking patterns. METHOD: Self-reported past
      drinking behavior and resulting consequences associated with specific occasions
      were assessed among 303 (66% women) college students. Students also estimated
      number of drinks associated with risk of experiencing future similar
      consequences. RESULTS: Paired-samples t tests indicated that students
      significantly overestimated the number of drinks it would take to vomit, have
      unwanted sexual experiences, experience hangovers, and black out in comparison
      with the actual self-reported number of drinks consumed the last time identical
      consequences were experienced. In addition, a series of multiple-regression
      analyses revealed that greater misperceptions between the perceived and actual
      number of drinks associated with each type of consequence were consistently
      associated with heavier drinking. CONCLUSIONS: Results suggest that heavier
      drinking students do not learn from their mistakes but instead overestimate the
      amount of alcohol they can consume without experiencing negative consequences.
      Clinical implications of these findings are discussed in terms of augmenting
      brief interventions aimed at heavy-drinking college students.

PMID- 16562410
TI  - Misperceptions of college student marijuana use: implications for prevention.
AB  - OBJECTIVE: This study investigates the relationship between marijuana use,
      perceived norms of use by friends and students in general, and negative
      experiences or problems from alcohol and drug use. It was hypothesized that
      students would overestimate the marijuana use of students in general and that
      perceptions about the prevalence of marijuana use would be related to drug
      related consequences. METHOD: In this study, 5,990 participants provided
      information on the perceptions and consequences of drug use via an online survey
      or via a paper-based survey. RESULTS: Although two thirds of participants
      reported no marijuana use, 98% of respondents incorrectly predicted that students
      in general use marijuana at least once per year. Perceptions of use by friends
      and students in general accounted for variance in drug use and related problems
      or experiences. CONCLUSIONS: Given the relationship between norm misperception
      and behavior with marijuana use, future research could explore the impact of
      targeting misperceived norms through prevention and intervention efforts.

PMID- 16562411
TI  - Event- and context-specific normative misperceptions and high-risk drinking: 21st
      birthday celebrations and football tailgating.
AB  - OBJECTIVE: Negative alcohol-related consequences often occur during specific
      events and in specific contexts (e.g., 21st birthday celebrations and tailgating
      parties). A lack of available event- and context-specific interventions suggests
      the need to better understand factors associated with heavy drinking in these
      contexts, with an eye toward developing specific interventions. The purpose of
      this research was to lay the foundation for developing personalized normative
      feedback interventions for 21st birthday celebratory drinking and tailgating
      drinking by evaluating whether students overestimate norms in these specific
      contexts, as they do more generally. METHOD: Perceived descriptive norms and
      alcohol consumption were assessed at event- and context-specific levels in two
      studies. Study 1 included 119 students turning 21 years old who reported their
      21st birthday drinking behavior and estimated the typical number of drinks
      consumed by students celebrating their 21st birthday. Study 2 included 140
      undergraduates drawn from a stratified random sample who reported their behavior
      regarding drinking and tailgating and their perceived norms for typical drinking
      and tailgating behavior. RESULTS: Results from Study 1 revealed that students
      overestimated peer drinking during 21 st birthday celebrations, and this
      overestimation was associated with heavier drinking on one's own 21st birthday.
      In Study 2, students underestimated the percentage of tailgaters who drank but
      overestimated typical consumption. Overestimation was consistently associated
      with heavier drinking during tailgating. CONCLUSIONS: Successful correction of
      general normative misperceptions has been shown to reduce drinking in other
      research. Documentation of normative misperceptions for specific events and
      contexts provided by these results represents an important step in developing
      event- and context-specific interventions utilizing specific normative feedback.

PMID- 16562412
TI  - Normative misperceptions and temporal precedence of perceived norms and drinking.
AB  - OBJECTIVE: Previous research has shown that students overestimate the drinking of
      their peers, and that perceived norms are strongly associated with drinking
      behavior. Explanations for these findings have been based largely on cross
      sectional data, precluding the ability to evaluate the stability of normative
      misperceptions or to disentangle the direction of influence between perceived
      norms and drinking. The present research was designed to evaluate (1) the
      stability of normative misperceptions and (2) temporal precedence of perceived
      norms and drinking. METHOD: Participants were college students (N = 164; 94
      women) who completed assessments of perceived norms and reported behavior for
      drinking frequency and weekly quantity. Most participants (68%) completed the
      same measures again two months later. RESULTS: Results indicated large and stable
      overestimations of peer drinking for frequency and weekly quantity. Results also
      showed that for weekly quantity, perceived norms predicted later drinking, but
      drinking also predicted later perceived norms. Results for frequency revealed
      perceived norms predicted later drinking, but drinking did not predict later
      perceived norms. CONCLUSIONS: These findings underscore the importance of
      longitudinal designs in evaluating normative influences on drinking. The present
      findings suggest that normative misperceptions are stable, at least over a
      relatively short time period. Findings support a mutual influence model of the
      relationship between perceived norms and drinking quantity but are more strongly
      associated with conformity explanations for the relationship between perceived
      norms and drinking frequency. Results are discussed in terms of implications for
      prevention interventions.

PMID- 16562413
TI  - Prevention of deaths from harmful drinking in the United States: the potential
      effects of tax increases and advertising bans on young drinkers.
AB  - OBJECTIVE: Harmful alcohol consumption is a leading cause of death in the United
      States. The majority of people who die from alcohol use begin drinking in their
      youth. In this study, we estimate the impact of interventions to reduce the
      prevalence of drinking among youth on subsequent drinking patterns and alcohol
      attributable mortality. METHOD: We first estimated the effect of public health
      interventions to decrease harmful drinking among youth from literature reviews
      and used life table methods to estimate alcohol-attributable years of life lost
      by age 80 years among the cohort of approximately 4 million U.S. residents aged
      20 in the year 2000. Then, from national survey data on transitions in drinking
      habits by age, we modeled the impact of interventions on alcohol-attributable
      mortality. RESULTS: A tax increase and an advertising ban were the most effective
      interventions identified. In the absence of intervention, there would be 55,259
      alcohol-attributable deaths over the lifetime of the cohort. A tax-based 17%
      increase in the price of alcohol of dollar 1 per six pack of beer could reduce
      deaths from harmful drinking by 1,490, equivalent to 31,130 discounted years of
      potential life saved or 3.3% of current alcohol-attributable mortality. A
      complete ban on alcohol advertising would reduce deaths from harmful drinking by
      7,609 and result in a 16.4% decrease in alcohol-related life-years lost. A
      partial advertising ban would result in a 4% reduction in alcohol-related life
      years lost. CONCLUSIONS: Interventions to prevent harmful drinking by youth can
      result in reductions in adult mortality. Among interventions shown to be
      successful in reducing youthful drinking prevalence, advertising bans appear to
      have the greatest potential for premature mortality reduction.

PMID- 16562414
TI  - Evaluating two brief substance-use interventions for mandated college students.
AB  - OBJECTIVE: This study evaluated two brief personal feedback substance-use
      interventions for students mandated to the Rutgers University Alcohol and Other
      Drug Assistance Program for Students (ADAPS): (1) a brief motivational interview
      (BMI) intervention and (2) a written feedback-only (WF) intervention. A key
      question addressed by this study was whether there is a need for face-to-face
      feedback in the context of motivational interviewing to affect changes in
      substance-use behaviors or whether a written personal feedback profile is enough
      of an intervention to motivate students to change their substance use. METHOD:
      The sample consisted of 222 students who were mandated to ADAPS, were eligible
      for the study, and completed the 3-month follow-up assessment. Eligible students
      completed a baseline assessment from which a personal feedback profile was
      created. They were then randomly assigned to the BMI or WF condition. Students
      were followed 3 months later. RESULTS: Students in both interventions reduced
      their alcohol consumption, prevalence of cigarette and marijuana use, and
      problems related to alcohol and drug use between baseline and follow-up. There
      were no differences between the two intervention conditions in terms of any
      substance-use outcomes. CONCLUSIONS: The results suggest that, under these
      circumstances and with these students, assessment and WF students changed
      similarly to those who had an assessment and WF within the context of a BMI.
      Given the fact that the former is less costly in terms of time and personnel,
      written profiles may be found to be a cost-effective means of reducing alcohol
      and drug use and related problems among low- to moderate-risk mandated college
      students. More research is needed with mandated students to determine the
      efficacy of feedback interventions and to isolate the effects of interventions
      from the effects of being caught and being reprimanded to treatment.

PMID- 16562415
TI  - Collecting data on alcohol use and alcohol-related victimization: a comparison of
      telephone and Web-based survey methods.
AB  - OBJECTIVE: Traditionally, personal contact with an experienced interviewer has
      been thought to facilitate collection of data on alcohol use and victimization
      experiences. Recent studies indicate that Web-based surveys may be an efficient
      alternative for gathering these sensitive data. To date, telephone interviewing
      and Web-based collection of data on alcohol-related negative consequences,
      particularly victimization, have not been compared. This study was designed to
      compare data from an interviewer-administered and Web-based survey on alcohol use
      and alcohol-related negative consequences in a sample of college women. METHOD:
      Seven hundred women from a second semester freshmen college class were randomly
      selected to participate in either the telephone interview or Web-based modes of
      survey administration. RESULTS: Fifty-three percent of invited women (N = 370)
      completed the survey. Completion rates were higher, and estimated dollar costs
      were significantly lower, for the Web-based survey. There were no differences in
      reported rates of alcohol or drug use by survey method; however, there were
      differences in several specific alcohol-related negative consequences.
      CONCLUSIONS: These findings suggest that, for college women, Web-based surveys
      versus telephone interviews can be an effective and more cost-efficient means for
      collecting data on alcohol use and related negative consequences, particularly
      victimization. In addition, we found some evidence that women may be more
      forthcoming when responding to a Web-based survey as compared with an interviewer
      administered telephone survey.

PMID- 16562416
TI  - The introduction of the heavy and frequent drinker: a proposed classification to
      increase accuracy of alcohol assessments in postsecondary educational settings.
AB  - OBJECTIVE: This study demonstrates the differences that exist within college
      drinkers identified as high-risk drinkers. METHOD: The study looked at alcohol
      and other drug (AOD) use patterns of the entire U.S. college student body, using
      a cross-section of institutions (public, private, 2-year, and 4-year) and
      students that reflected the enrollment patterns within geographic regions of the
      country. A survey that focused on safety and violence on college campuses, in
      addition to more traditional questions regarding the prevalence of alcohol and
      other drug use and negative consequences, was mailed to a stratified random
      sample. The final sample consisted of students from 96 institutions of higher
      education (N = 17,821; 45.3% males, 54.7% females) and was weighted to ensure an
      accurate representation of the student population in the United States. RESULTS:
      We found there to be a broad range of problematic drinkers grouped together
      within the category "heavy drinking," which is defined by a single episode (five
      or more drinks on one occasion). The seriously problematic drinkers can be
      differentiated from those less problematic by the inclusion of frequency in the
      criteria. Comparing heavy drinkers with "heavy and frequent drinkers," we found
      rates of negative consequences to be almost three times higher for the heavy and
      frequent drinkers. In addition, the heavy and frequent drinkers account for
      nearly half of all negative consequences reported by all drinkers. CONCLUSIONS:
      Greater specificity in classification is a necessary component of alcohol
      research and intervention.

PMID- 16562417
TI  - A within-subjects validation of a group-administered timeline followback for
      alcohol use.
AB  - OBJECTIVE: The current study uses a within-subjects randomized design with the
      Timeline Followback (TLFB) method administered in groups or to individuals to
      determine the equivalence of these methods. METHOD: One hundred and four male and
      female college students who reported drinking at least once in the past 3 months
      completed the TLFB during a one-on-one interview, as well as in a group setting
      days apart. The two administrations were counterbalanced among the participants.
      Drinking variables assessed were drinking days, average drinks, total drinks, and
      maximum drinks consumed both during a 3-month (90 days) and a 1-month (30 days)
      period. RESULTS: Repeated measures analyses revealed no differences within
      subjects between the individual TLFB and the group TLFB on any of the four
      assessed drinking variables in the past 3 months and the past 1 month. Pearson's
      correlation coefficients revealed strong and significant correlations between the
      two administration styles. Heavy episodic drinking behavior was similar across
      administration styles as well. No differences between administration styles were
      consistent regardless of which administration was received first. CONCLUSIONS:
      The study suggests that the group TLFB yields similarly accurate results to the
      previously validated individual TLFB. The group-administered TLFB could be used
      in clinical and research settings as an efficient means of collecting information
      from large numbers of individuals.

PMID- 16562418
TI  - The Scottish Medical Journal--the first fifty years.
AB  - The Scottish Medical Journal has been published for half a century and its pages
      reveal not only the steady changes in Scottish medical care and careers, but also
      reflect the attitudes of the times. The Journal has survived a number of crises.
      Recent changes, both at the Journal and in Scottish politics, leave it well
      placed for an expanded and important place in Scottish medicine.

PMID- 16562419
TI  - The health service in a devolved Scotland.

PMID- 16562420
TI  - The relationship between volume and health outcomes--a review.

PMID- 16562421
TI  - Undergraduate medical education in Scotland, 1955 and 2005.

PMID- 16562422
TI  - The new Glasgow medical and dental graduation declaration.
AB  - The medical and dental graduation ceremony at the University of Glasgow in July
      2003 marked not only the 300th anniversary of the first Glasgow medical
      graduation, but also the first major revision of the graduation oath. This paper
      records the process, and explains the reasons, behind the revision of the oath
      and the introduction of a new graduation declaration. The new declaration
      provides continuity with the past, while addressing current and future challenges
      for professionalism in medicine.

PMID- 16562423
TI  - An audit of the management of melanoma patients at Glasgow Royal Infirmary 1998
      2003.
AB  - BACKGROUND: Melanoma is an important cause of morbidity and mortality. Recently
      published Scottish Intercollegiate Guideline Network (SIGN) guidelines outline
      standard management for melanoma patients in Scotland. METHODS: We audited the
      management of consecutive patients diagnosed with melanoma in Glasgow Royal
      Infirmary (1998-2003), using the SIGN guidelines as a gold standard. RESULTS: Of
      102 patients, 41% were male and 59% were female. The mean ages of men and women
      were 58 and 50 years respectively. Fifty five per cent of all patients had a
      superficial spreading melanoma, and the median Breslow thickness was 0.64 mm. The
      most commonly affected site was the head and neck (29%). Most patients (87%) were
      referred by their general practitioner, but only 30% were marked as urgent by the
      referrer, and accordingly the median time to first appointment varied between 20
      days (1998) and 52 days (2001). The most frequently noted suspicious feature was
      irregular pigmentation. The median time to biopsy was 6 days. Seventy-one per
      cent of patients had an excision biopsy, and of those who did not, most (71%) had
      lesions on the head and neck. There was poor recording of surgical margins (13%)
      and histological margins were used to determine the need for re-excision. The
      SIGN guidelines for re-excision and sentinel lymph node biopsy were closely
      followed. CONCLUSION: The SIGN guidelines for melanoma have been adhered to in
      our department, although time to first appointment exceeded national
      recommendations.

PMID- 16562424
TI  - Changing prevalences of overweight and obesity in primary school children--a
      glimmer of hope?
AB  - BACKGROUND: The current epidemic of childhood obesity is a growing public health
      concern. Estimates of the prevalence of obesity are necessary so that secular
      trends can be monitored and the need for preventative measures assessed. AIMS: To
      establish the prevalences of overweight and obesity in Aberdeen primary
      schoolchildren and to investigate how children have been changing with respect to
      body fatness during their primary school years. METHODS: Retrospective study of
      two cohorts of school entrants, using height and weight data from school nurse
      records. RESULTS: Data were collected on 1018 children. The prevalence of
      overweight among children in primary year 1 decreased from 28.7% in 1997/98 to
      21.5% in 2001/02 (P<0.01). The mean BMI SD score also significantly decreased in
      boys from 0.51 in 1997/98 to 0.32 in 2001/02. For the 1997/98 school entrants,
      the prevalences of overweight and obesity did not change between school entry and
      the end of primary school. The mean BMI SD score decreased significantly during
      primary school in boys but not in girls. CONCLUSION: Although childhood
      overweight and obesity remain major public health concerns, we report a slight
      improvement in measures of obesity over time, particularly in boys.

PMID- 16562425
TI  - Prospective study of laparoscopic adjustable gastric banding in the west of
      Scotland.
AB  - Obesity is an increasing problem in Scotland and Laparoscopic Adjustable Gastric
      Bands (LAGB) are an effective method of weight reduction. Most outcome data are
      reported from high volume units with extensive experience or dedicated bariatric
      practice. We aimed to assess an experienced laparoscopic surgeon's outcome
      working outwith a dedicated bariatric practice in the west of Scotland. METHODS:
      All LAGB procedures performed by a single surgeon were prospectively assessed
      from 1997 to 2004. LAGB were inserted using pars flaccida approach. Patient
      selection was based on BMI >35 or significant obesity related co-morbidities.
      Outcomes included percentage excess weight loss (%EWL) and excess BMI loss (EBL).
      We assessed total operating time to assess the learning curve for LAGB placement.
      RESULTS: 125 patients were assessed (107 F:18 M). 123 patients were in regular
      follow-up (98%). Median age was 44 years (range 25-63). Mean follow-up was 34
      months (range 11-91). Median initial BMI was 49 (range 37-73). 31% were BMI 35
      45, 36% were BMI 45-50 and 33% were BMI>50. %EWL at 1,3 and 5 years was 45, 58
      and 74, respectively. EBL at 1, 3 and 5 years was 11.7, 16.1, and 21.7,
      respectively. Complications included 4 converted procedures, 1 failed band
      insertion after conversion and re-operation for removal in five. Eight patients
      had tubing access port problems requiring intervention. The median overall total
      operation time was 80 minutes (range 50 - 160). CONCLUSIONS: In this cohort LAGB
      insertion by an experienced laparoscopic surgeon is safe with few re-operations.
      Satisfactory weight loss is obtained and patient compliance with follow-up is
      high.

PMID- 16562426
TI  - Colorectal cancer--a disease that can be conquered.

PMID- 16562427
TI  - James H Nicoll, MB, CM Glasg, FRFPS Glasg. Legion of Honour France, father of day
      surgery.

PMID- 16562428
TI  - Sir William Osler (1849-1919): his opinion of modern therapeutics.

PMID- 16562429
TI  - The audit cycle: a guide to success.

PMID- 16562430
TI  - Waking up to sleep disorders.

PMID- 16562431
TI  - Fifty years of the confidential enquiry into maternal deaths.

PMID- 16562432
TI  - Improving maternal safety in future: learning from the confidential enquiries.

PMID- 16562433
TI  - Stroke in pregnancy.

PMID- 16562434
TI  - Treating learned helplessness in hospital: a reacquaintance with self-control.

PMID- 16562435
TI  - Targeting smokers in the hospital setting.

PMID- 16562436
TI  - Time management.

PMID- 16562437
TI  - Joint and soft tissue aspiration and injection.

PMID- 16562438
TI  - How to perform a lumbar puncture with the patient in the seated position.

PMID- 16562439
TI  - Interpretation of wrist and hand radiographs.

PMID- 16562440
TI  - A sinus tachycardia and chest pain.

PMID- 16562441
TI  - The ischaemic leg.

PMID- 16562442
TI  - So you want to be...a medical oncologist.

PMID- 16562443
TI  - Cutaneous manifestations of lung disease.

PMID- 16562444
TI  - Flexible training: how do trainees perceive the application process?

PMID- 16562445
TI  - Hyper-elevated prostate-specific antigen levels are not always carcinoma.

PMID- 16562446
TI  - An unexpected finding during gastroscopy.

PMID- 16562447
TI  - Jejunojejunal intussusception as a result of submucosal lipoma.

PMID- 16562448
TI  - An unusual case of polyuria in a lithium-treated patient.

PMID- 16562449
TI  - Meat and two veg.

PMID- 16562450
TI  - Sir David Bruce, a pioneer of tropical medicine.

PMID- 16562451
TI  - Treating depression in patients with physical disease.

PMID- 16562453
TI  - Time for a financial health check.

PMID- 16562452
TI  - Educational supervision for the foundation programme.

PMID- 16562454
TI  - Does total intravenous anaesthesia increase the risk of awareness?

PMID- 16562455
TI  - Casebook: hypertension.

PMID- 16562456
TI  - Myocardial infarction.

PMID- 16562457
TI  - From: Dr Christina Green subject: casebook: menorrhagia, The Practitioner,
      January 2006.

PMID- 16562458
TI  - From: Dr Victoria Holt subject: casebook: menorrhagia, The Practitioner, January
      2006.

PMID- 16562459
TI  - From: Dr Trevor Stammers subject: Caring for women seeking abortion, The
      Practitioner, January 2006.

PMID- 16562461
TI  - [To serve the people's health and economic development--the 55th anniversary of
      the National Institute of Parasitic Diseases].

PMID- 16562462
TI  - [Immunodiagnosis of Schistosoma japonicum infection in China: review and
      prospects].

PMID- 16562463
TI  - [Global significance of the elimination of lymphatic filariasis in China].

PMID- 16562464
TI  - [A national survey on current status of the important parasitic diseases in human
      population].
AB  - In order to understand the current status and trends of the important parasitic
      diseases in human population, to evaluate the effect of control activities in the
      past decade and provide scientific base for further developing control
      strategies, a national survey was carried out in the country (Taiwan, Hongkong
      and Macau not included) from June, 2001 to 2004 under the sponsorship of the
      Ministry of Health. The sample sizes of the nationwide survey and of the survey
      in each province (autonomous region and municipality, P/A/M) were determined
      following a calculating formula based on an estimation of the sample size of
      random sampling to the rate of population. A procedure of stratified cluster
      random sampling was conducted in each province based on geographical location and
      economical condition with three strata: county/city, township/town, and spot,
      each spot covered a sample of 500 people. Parasitological examinations were
      conducted for the infections of soil-transmitted nematodes, Taenia spp, and
      Clonorchis sinensis, including Kato-Katz thick smear method, scotch cellulose
      adhesive tape technique and test tube-filter paper culture (for larvae). At the
      same time, another sampled investigation for Clonorchis sinensis infection was
      carried out in the known endemic areas in 27 provinces. Serological tests
      combined with questionnaire and/or clinical diagnosis were applied for hydatid
      disease, cysticercosis, paragonimiasis, trichinosis, and toxoplasmosis. A total
      sampled population of 356 629 from the 31 P/A/M was examined by parasitological
      methods and 26 species of helminth were recorded. Among these helminth, human
      infections of Metorchis orientalis and Echinostoma aegypti were detected in
      Fujian Province which seemed to be the first report in the world, and Haplorchis
      taichui infection in Guangxi Region was the first human infection record in the
      country. The overall prevalence of helminth infections was 21.74%. The prevalence
      of soil-transmitted nematodes was 19.56% (including hookworm infection 6.12%,
      Ascaris infection 12.72% and Trichuris infection 4.63%), and the estimated number
      of population infected with soil-transmitted nematodes was 129 million (with
      39.3, 85.93 and 29.09 million for hookworm, Ascaris and Trichuris infections
      respectively). The prevalence of Taenia infection was 0.28% with an infected
      population of 550 000. The prevalence of Clonorchis sinensis in the national
      survey was 0.58%. From the survey in the known Clonorchis endemic areas with a
      sample of 217 829, terobius vermicularis infection in children under 12 years old
      was 10.28%. The positive rate of serological tests for hydatid disease,
      cysticercosis, paragonimiasis, trichinosis, and toxoplasmosis was 12.04% (4
      796/39 826), 0.58% (553/96 008), 1.71% (1 163/68 209), 3.38% (3 149/93 239) and
      7.88% (3 737/47 444) respectively. In comparison to the last national survey in
      1990, the prevalence of hookworm, Ascaris lumbricoides and Trichuris trichiura
      infections has been reduced by 60.72%, 71.29% and 73.60% respectively, and the
      number of infected people by soil-transmitted nematodes has declined remarkably.
      However, the prevalence of Clonorchis infection significantly increased in the
      provinces of Guangdong, Guangxi and Jilin by 182%, 164% and 630% respectively. A
      remarkable increase of the prevalence of Taenia infection was found in Sichuan
      and Tibet, by 98% and 97% respectively. Echinococcosis is important in the
      Western part of China. Many parasitic diseases are still highly prevalent in the
      rural and pastoral areas with higher prevalence, morbidity and certain case
      fatality in farmers and herdsmen, especially in women and children.

PMID- 16562465
TI  - [An inspiration from the outbreaks of angiostrongyliasis cantonensis].

PMID- 16562466
TI  - [Epidemiological trends and control measures of trichinellosis in China].

PMID- 16562467
TI  - [Features and trends in the development of parasitology].

PMID- 16562468
TI  - [Drug resistance of Plasmodium and rational application of antimalarials].

PMID- 16562469
TI  - [Research progress and prospects for vaccines against parasitic diseases].

PMID- 16562470
TI  - [New challenges to medical parasitology: emerging and re-emerging diseases].

PMID- 16562471
TI  - [Non-specific mite infestation].

PMID- 16562472
TI  - [Immunological research progress in opportunistic protozoan infections].

PMID- 16562473
TI  - [Cloning, location and differential analysis of transcription factor Relish gene
      from Anopheles stephensi under different feeding conditions].
AB  - OBJECTIVE: To clone, locate and differentially analyze the transcription factor
      Relish gene from Anopheles stephensi, and to examine its signals-modulating
      action on prophenoloxidase cascade and melanization of Plasmodium yoelii oocysts.
      METHODS: Relish cDNA of total mosquitoes was amplified by RT-PCR with degenerated
      primers. Target PCR product was purified, cloned, sequenced and identified.
      Special Relish gene was amplified with specific primers from hemocytes or midgut,
      respectively. Semi-quantitative analysis was made under different feeding
      conditions. Relish message ribonucleic acid was identified with hybridization in
      situ. RESULTS: One cDNA segment of Relish similar to An. gambiae was acquired
      from An. stephensi. The same Relish gene was also manifested in the hemocytes and
      midgut. Marked up-regulation expression of Relish was observed at 6, 12, 24 or 48
      h of Plasmodium yoelii infection and at 12 and 24 h after sucking nitroquine
      acetate sucrose solution, that was before inducible oocyst melanization. Relish
      was also expressed in the hemocytes and midguts by ISH. CONCLUSION: Transcription
      factor Relish of An. stephensi might play a role in signal modulation of
      Plasmodium yoelii infection and oocyst melanization.

PMID- 16562474
TI  - [Studies on susceptibility of Pomacea canaliculata of different developmental
      stages to infection with Angiostrongylus cantonensis].
AB  - OBJECTIVE To study the susceptibility of Pomacea canaliculata of different
      developmental stages to Angiostrongylus cantonensis infection. METHODS: P.
      canaliculata snails breeding at laboratory were divided into four rank (I-IV)
      according to the weight, and infected with the first stage larvae of A.
      cantonensis from Fujian Province. Their mortality, infection rate, worm burden,
      and the size, development and distribution of larvae in snails were examined.
      RESULTS: Snails at different developmental stages were readily infected with A.
      cantonensis. The infection rate was between 76% and 100%, with no significant
      difference among the groups (P>0.05). Snails at earlier developmental stage
      showed higher mortality. The heaviest worm burden and the largest number of
      snails harboring more than 100 larvae were found in snails of rank III. In
      general the larvae in snails showed a synchronous development in the groups.
      Sizes of the third stage larvae in snails of various ranks were homogeneous. The
      period before the third stage larva emergence and the time for a peak percentage
      of the larvae exhibited no significant difference among the four ranks. The
      larvae widely distributed in various parts of snails, with more in the lung and
      foot, and larvae from snails of different ranks could all infect rats
      successfully. CONCLUSION: P. canaliculata of the four ranks can all be infected
      by the first stage larvae of A. cantonensis. Rank III snails may be better for
      studying the relationship between P. canaliculata and A. cantonensis. The
      potential role of young snails in angiostrongyliasis transmission should be
      recognized.

PMID- 16562475
TI  - [Immunological characteristics induced in mice by nucleic acid vaccine harboring
      the gene encoding GAPDH in Schistosoma japonicum].
AB  - OBJECTIVE: To study the immunological characteristics induced in C57BL/6 mice by
      nucleic acid vaccine harboring the gene encoding glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) of Schistosoma japonicum. METHODS: The gene encoding GAPDH
      of S. japonicum from screening of cDNA library was amplified using universal
      primer T3 promoter and T7 promoter, the PCR product was cloned into the T-A
      vector pT-Adv. GAPDH-pT-Adv and eukaryotic expression vector pcDNA3 were digested
      by restriction endonucleases Hind III and Xho I, and the nucleic acid vaccine
      harboring the gene encoding GAPDH was then constructed by ligating the digested
      products. C57BL/6 mice were immunized using the purified pcDNA3-SjGAPDH. The
      expression of GAPDH in local muscle in mice was examined by immunofluorescence
      assay. The specific characteristics induced by pcDNA3-SjGAPDH were analyzed using
      SDS-PAGE, Western blotting, and ELISA respectively. RESULTS: Light green
      fluorescence was observed in local muscle cell under the fluoroscope 24 and 48
      hours after immunization, which indicated the expression of GAPDH. The
      recombinant plasmid induced specific anti-GAPDH IgG, predominantly IgG2a, IgG2b
      and IgG3. Cytokines IFN-gamma, IL-2 but IL-4 were detected in C57BL/6 mice
      vaccinated with the vaccine. CONCLUSION: The DNA vaccine, pcDNA3-SjGAPDH induces
      Th1 type immune response in mice.

PMID- 16562476
TI  - [Relationship of the intensity of Schistosoma japonicum infection to the
      variation in individual egg count].
AB  - OBJECTIVE: To investigate the relationship of the intensity of Schistosoma
      japonicum infection with the variation in individual egg counts. METHODS: Stool
      specimens were collected from residents in a village in Jiangxi Province and
      examined with Kato-Katz thick smear method for seven consecutive days. Two smears
      were prepared and microscopically examined for each specimen. 570 individuals
      completed the investigation. Coefficient of variation (CV) was used to assess the
      intra-individual variation of the egg counts, in relation to the demographic
      characteristics including age, sex, occupation, and the intensity of infection.
      RESULTS: The proportion of individuals with at least one positive finding
      increased from 33.0% in a single measurement to 56.5% by seven measurements
      (P<0.01). The average intensity of infection in a single Kato-Katz test (111.06
      EPG) was markedly higher than the average accumulated intensity of infection
      (42.51 EPG). Variation of intra-individual: the variation of CV in female
      infected subjects was higher than males (P<0.05). The variation of CV in 0-9 age
      group was higher than other age groups (P<0.05). The lowest variation of CV was
      detected in fishermen (P<0.05), but no statistical difference was found among
      other occupation groups. With an increase of the intensity of infection, the
      variation of CV decreased gradually. A negative correlation was observed between
      the variation of CV and the intensity of infection(r=-0.717, P<0.01). There was
      no significant difference in variation of CV between males and females, age and
      occupation groups when data were stratified according to the intensity of
      infection (P>0.05). CONCLUSION: The prevalence and intensity of S. japonicum
      infection by single Kato-Katz test was obviously lower than the real figures. The
      intensity of infection may be an essential factor that affects the intra
      individual variation of egg counts.

PMID- 16562477
TI  - [A discussion on the CSP genotyping of Plasmodium vivax and malaria control in
      five southern provinces of China].
AB  - OBJECTIVE: To explore circumsporozoite protein (CSP) genotype structure of
      Plasmodium vivax in southern China and evaluate its epidemiological significance.
      METHODS: Filter paper blood samples were collected from 346 vivax malaria
      patients in 5 provinces (Autonomous Region) including Hainan, Yunnan, Guangxi,
      Guangdong and Guizhou for identifying CSP genotypes, by using the method of
      single-tube nested/multiplex PCR. The findings combined with relevant data were
      statistically analyzed. RESULTS: In Guangdong, Guangxi and Guizhou Provinces
      (Autonomous Region), the temperate zone family strains accounted for more than
      90%, with only a few tropical zone family strains and no PV-type II each strain.
      In Yunnan Province, temperate strains and tropical strains accounted for 71.4%
      and 28.6% respectively, with occasional PV-type II strain. In Hainan Province,
      strains of temperate zone, tropical zone and PV-type II accounted for about one
      third. CONCLUSIONS: The temperate zone family strains were the predominant ones
      in the Provinces (Autonomous Region) of Guangdong, Guangxi and Guizhou where
      malaria control was carried out effectively; while in Hainan and Yunnan Provinces
      the difficulties in malaria control may probably be related to the complex
      structure of P. vivax population and multiple infections of different genotypes.
      The findings indicate that the complexity of the P. vivax genotype structure
      might be an indicative epidemiological feature for malaria control and
      surveillance.

PMID- 16562478
TI  - [Analysis of molecular profiles among Trypanozoon species and subspecies by MGE
      PCR method].
AB  - OBJECTIVE: To analyze the relationship between genetic variability and evolution
      among Trypanosoma brucei (including T. b. brucei, T. b. rhodesiense and T. b.
      gambiense), T. evansi and T. equiperdum isolates. METHODS: Genomic DNAs of 26
      trypanosome isolates were amplified by a mobile genetic elements (MGE) -PCR
      technique and cluster analysis was performed based on the molecular profiles with
      Neighbor-Joining method. RESULTS: The genetic variability among trypanosome
      isolates examined was obvious with an average genetic distance of 41.2% (ranged
      from 0 to 100%). Similarity coefficient among T. brucei isolates was 41.15% which
      was lower than that between T. evansi and T. equiperdum isolates. The closest
      relationship was found between T. evansi and T. brucei isolates with a similarity
      coefficient of 62.94%. The genetic variability between T. b. rhodesiense and T.
      b. brucei isolates was higher than that among T. b. gambiense isolates.
      CONCLUSION: Species and subspecies in Trypanozoon displayed a higher genetic
      variability; T. equiperdum isolates collected from China and from South America,
      and T. evansi isolates from China and from South America, should have a similar
      origin.

PMID- 16562479
TI  - [Survey on the current status of important human parasitic infections in Fujian
      province].
AB  - OBJECTIVE: To understand the prevalence of important human parasitic diseases in
      Fujian province. METHODS: According to the national guidelines, clustered random
      sampling was made for the survey. Modified Kato-Katz thick smear was applied to
      examine helminth eggs for soil-transmitted nematodes and Clonorchis sinensis.
      Cellophane and swab technique was applied for detecting Enterobius vermicularis
      eggs in children under 12. Questionnairing, skin test, serological test and
      eosinophil examination were carried out for Paragonimus infection.
      Questionnairing and serological test were used for Taenia infection and
      cysticercosis. Retrospective investigation was conducted with the data on
      outpatient and hospitalized cases with parasitic diseases. RESULTS: 45,736 people
      at 73 spots of 24 counties were investigated and 14 species of parasites were
      found. The overall infection rate of intestinal helminth infections was 36.15%.
      The prevalence of Ascaris lumbricoides, hookworms and Trichuris trichiura was
      9.55%, 19.73% and 11.48% respectively. The infection rate of Enterobius
      vermicularis and Clonorchis sinensis was 22.06% and 0.60% respectively. The
      positive rate of skin test and serological test among skin test positives for
      Paragonimus infection was 7.07% and 9.23% respectively. The serology positive
      rate for cysticercosis was 2.28%, only 3 cases of taenia infection were found
      from 16371 persons investigated. Human infections with Angiostrongylus
      cantonensis, Diphyllobothrium latus, Taenia saginata, and Gnathostoma spinigerum
      were found for the first time in the Province. Metorchis orientalis and
      Echinostoma aegyptiaca infections in human were first recorded. CONCLUSION: The
      overall prevalence of soil-transmitted nematodes has decreased significantly in
      the province, although still highly prevalent in social-economically less
      developed areas. Meanwhile, attention should be paid to the food-borne parasitic
      infections in human population.

PMID- 16562480
TI  - [Scanning electron microscopy of Paragonimus proliferus].
AB  - OBJECTIVE: To identify the species of Paragonimus proliferus with scanning
      electron microscopy (SEM) based on the surface structure of excysted
      metacercariae, adult worms and eggs. METHODS: Crabs were collected from the
      endemic area of P. proliferus and excysted metacercariae were separated. Adult
      worms at different ages and eggs were obtained from the experimentally infected
      rats. After being fixed by 2.5% glutardialdehyde and 1% osmic acid, alcohol
      dehydration, gilded by ion spatter, the specimens were observed under SEM by
      STEREOSCAN-100. RESULTS: The cuticular spines of excysted metacercariae
      distributed in single pattern, bayonet-shaped or scale-shaped. There were 6 dome
      shape papillae around the rim of the ventral sucker symmetrically arranged. The
      cuticular spines of different age adult worms distributed in group pattern,
      relatively denser and more regularly arranged in the anterior part than the
      posterior part of the worm body. The shape and arrangement of the cuticular
      spines on adult worms at different ages were basically uniform. The surface of
      eggshell including the operculum was generally smooth. The shell rim joining the
      operculum was thick and prominent. A knot-like prominence was observed at the
      aboperculum end. CONCLUSION: The cuticular spines of both excysted metacercariae
      and adult worms of P. proliferus show its own characteristics, but the size and
      shape of the cuticular spines among individuals or different parts of the same
      specimen show certain differences.

PMID- 16562481
TI  - [Effect of dihydroartemisinin on ultrastructure of Giardia lamblia in vitro].
AB  - OBJECTIVE: To study the in vitro effect of dihydroartemisinin (DHA) on Giardia
      lamblia. METHODS: Trophozoites of G. lamblia were cultivated with modified TYI-S
      33 medium that contains dihydroartemisinin (DHA). The trophozoites were
      morphologically observed respectively with light and electron microscopes after
      treated with the drug. RESULTS: The mortality increased with the prolongation of
      the time of the drug action and the increase of drug concentration (P<0.01).
      While at the same concentration of 100 microg/ml, the mortality increased from
      46.6% for 12 h to 100% for 24 h (P<0.05). For 12 h, the mortality of G. lamblia
      was from 46.6% at concentration of 100 microg/ml to 100% at 200microg/ml. Under
      optical microscope, deformation and swelling of the parasites were observed when
      treated with DHA for 12, 24 and 48 h. Movement of the flagella became slow or
      stopped. Under electron microscope, the trophozoites were swollen and deformed,
      vacuoles were seen in the cytoplasm, and the cell membrane ruptured and fell off.
      The cytoplasm protrusions appeared on the surface of the plasma membrane. The
      adhesive disc changed into large bubbles and the perinuclear space became wider
      and the deformed nucleus was seen. CONCLUSION: DHA shows a strong impairment on
      the plasma membrane and cytoskeleton of Giardia lamblia.

PMID- 16562482
TI  - [Expression, purification and identification of Echinococcus granulosus
      recombinant antigen B].
AB  - OBJECTIVE: To purify and identify recombinant antigen B of hydatid disease.
      METHODS: The recombinant plasmid pMalc2x-AgB was expressed in E. coli JM109. The
      fusion protein rAgB-MBP was made up of antigen B and MBP (maltose binding
      protein) which was designed to absorb the antigen B onto the amylose column. In
      order to get the pure antigen as the probe for selecting phage displayed antibody
      library, factor Xa protease was used to digest the fusion protein rAgB-MBP so
      that MBP was cut off from the special cleavage site. Flowing through the amylose
      resin column and hydroxyapatite column, rAgB was purified by the method of
      affinity chromatography. Its specificity was proved by patient sera with Western
      blotting. RESULTS: The recombinant antigen B was Mr 12 000, and it showed the
      capability to combine with the specific antibody. CONCLUSION: Hydatid disease
      antigen B can be produced by molecular method and applied in monoclonal antibody
      production and phage antibody library scanning.

PMID- 16562483
TI  - [Study on the strategy of interrupting schistosomiasis transmission in a hilly
      new endemic area of Taoyuan County].
AB  - OBJECTIVE: To develop a strategy for interrupting the transmission of
      schistosomiasis japonica in a hilly new endemic area. METHODS: Since 1996,
      chemotherapy with praziquantel (adult 40 mg/kg, child 50 mg/kg, cattle 30 mg/kg,
      once a year) on human beings in Taoyuan County who had ever contacted with
      infectious water and cattle which were herded in endemic situation was the major
      intervention, with focal control of Oncomelania snails in susceptible areas as
      supplementary one. RESULTS: The positive rate of stool examination for
      schistosomiasis in human and cattle reduced from 5.69% and 6.76% in 1996 to 0.04%
      and 0 in 2005 respectively. The positive rate of indirect hemagglutination test
      (IHA) in human dropped from 7.45% in 1996 to 1.61% in 2004. Though living snails
      were still found in most habitats, the density of infected snails decreased from
      0.0036/0.11m2 in 1997 to 0 in 2005 and no infected snails were found since 2000.
      CONCLUSION: Due to less movement of human and cattle populations and the hilly
      area relatively isolated, chemotherapy combined with focal mollusciciding have
      been highly effective in eliminating the infection sources and interrupting
      transmission of schistosomiasis.

PMID- 16562484
TI  - [Assessment of disease burden and its application].

PMID- 16562485
TI  - [Research progress on the origin, function and biological characteristics of
      hydrogenosome of Trichomonas spp].

PMID- 16562486
TI  - [Observation on biochemical indices in experimental infection with Taenia
      saginata].

PMID- 16562487
TI  - [Determination of schistosomiasis high-risk zone by using sentry mouse method].

PMID- 16562488
TI  - [Study on soluble antigens of Pagumogonimus skrjabini by SDS-PAGE and two
      dimensional gel electrophoresis].

PMID- 16562489
TI  - [Study on strategy of filariasis control in Heze City].

PMID- 16562490
TI  - [Application of digital mutual communication system in teaching of parasitologic
      experiment].

PMID- 16562491
TI  - [Wooden models of human skeleton made in Edo era, Japan, with special reference
      to Hoshino wooden skeleton].
AB  - The wooden model of the human skeleton, called wooden skeleton, is a
      distinguished original craft object in Edo era (1600-1867), Japan, when medical
      doctors were unable to keep the human skeleton for their study and teaching
      purpose. There are three kinds of wooden skeletons, i. e. Hoshino, Kagami and
      Okuda wooden skeletons made in 1792, 1810 and 1820, respectively. The former two
      are of adult male and the latter of female. They were made in surprising accuracy
      as compared with figures appeared in medical books available in Japan at that
      time, which suggests scientific readiness of the doctors and skills of the
      craftsmen. A complete set of the skeleton, except for the hyoid bone, has been
      preserved for Hoshino and Okuda wooden skeletons, while several bones have been
      missing in Kagami wooden skeleton. Each bone of Hoshino and Kagami wooden
      skeletons was made separately and connected by a tenon and a corresponding
      mortise at the articular surface. So it is hardly considered that all wooden
      bones were assembled into the whole body skeleton on use. Okuda wooden skeleton,
      on the other hand, was made for being shown in sitting position. The skull of
      Hoshino wooden skeleton is of special interest: the skull cap is not open, yet
      the internal structures of the skull, such as the sella turcica, foramina for
      nerves and vessels, and sulci for venous sinuses were made in considerable
      accuracy. Moreover, the proper connection of most foramina was proved between the
      inside and outside of the skull. The skull caps of Kagami and Okuda wooden
      skeletons are open as those used in the modern medical education.

PMID- 16562492
TI  - [Okuda wooden human skeleton made in Edo era, Japan].
AB  - Probably in 1820 (late Edo era), a human skeleton for medical education was
      carved from cypress wood, based on a criminal's skeleton under the supervision of
      a medical doctor, Banri Okuda in Osaka City. The skeleton is called "Okuda wooden
      skeleton" and is now housed in the National Science Museum, Tokyo. The bones can
      be assembled into a skeleton by metal pivots or bamboo sticks. The thorax and
      pelvis were made of several pieces of wood and combined together, respectively.
      By and large, the wooden skeleton shows morphological characteristics usually
      seen in early middle-aged females of the Edo era. But the claviculae, distal ends
      of the femora, and the patellae are exceptionally larger than those of a female,
      implying that these bones of the original skeleton had already been lost or were
      deformed before the wooden skeleton was made. Actually the wooden skeleton might
      not have been used for medical education but rather for the promotion of European
      medicine, which was gradually developing in the Edo era.

PMID- 16562493
TI  - [Envisioning the inner body in Edo-Japan: Inshoku yojo kagami and Boji yojo
      kagami].
AB  - There are two ukiyoe, Japanese woodblock prints, presumed to have been produced
      around 1850 by the artist Utagawa Kunisada (1786-1864), or possibly, an
      understudy at his shop. One of the two ukiyoe, titled Inshoku yojo kagami (Rules
      of Dietary Life) shows a man drinking sake, holding a goblet in his hand. The
      other, titled Boji yojo kagami (Rules of Sexual Life) shows a woman, apparently a
      courtesan, holding a tobacco pipe to her mouth. These prints give a good picture
      of the images of the inside of human body, which were widely accepted among the
      common people after the end of the seventeenth century in the Edo period, because
      ukiyoe was a popular art produced by the common people in the Edo period, and the
      market for ukiyoe prints was primarily the general populace of the cities. The
      contrivance of the two Rules of Life prints lies in their fusion of two formats.
      One is the format of see-through body displaying the internal organs. The other
      is that of explaining the functions of the various internal organs in the form of
      familiar scenes from the living space of cities and households. Miniature
      sketches of people at work can be seen in them, performing the tasks believed to
      be that of each organ. By observing the work being carried out by the people, one
      could understand the organ's function. The purpose of the two annotated prints is
      explained in the notes as twofold. One was to educate viewers about the functions
      of the five viscera and six entrails, i.e., the principal inner organs in the
      traditional East Asian conception of the body. The other was to admonish them
      against excessive eating, drinking and sexual intercourse.

PMID- 16562494
TI  - [Chemical content analysis of specimens of human head temporal portion
      commercially distributed for otological surgery lessons].
AB  - Specimens of the human head temporal portion are provided in the United States
      and distributed commercially for lessons in otological surgery via the internet.
      Many otologists have obtained and used these specimens in Japan. According to our
      chemical content analysis, these specimens were found to contain harmful
      substances as well as large molecule aldehydes and fatty acid methylesters, which
      are not or only rarely included in the human cadaveric specimens prepared in
      Japan. We discuss the suggested treatment of these imported specimens, how trial
      preparation of specimens are much better than the imported items, and the
      background of the rapid and wide distribution of the imported items in Japan.

PMID- 16562495
TI  - [Leprosy and medicine I--proposal of an isolation policy and its background].
AB  - The leprosy policy of Japan began from when the government enacted "law No. 11
      (The leprosy prevention act)" in 1907 (Meiji 40) and several leprosy sanatoriums
      were built and the patient who wanders about was received. Then, in rise of
      totalitarianism, the isolation policy of Japan gained national support under a
      slogan "Patient Relief", and it would become the big factor to which enactment of
      "Leprosy Prevention Law" in 1931 (Showa 6) and leprosy policy changed to
      segregation which aimed at internment of all leprosy patients. From today's
      research on the leprosy policy of Japan, it is internment of all leprosy
      patients, whole life isolation, social defense and neglect of patients' human
      rights and led to many tragedy of patient. However, there is little research
      which can reply clearly to the question of whether the leprosy policy of Japan
      was really original and what the factors of led to the formation of the
      segregation policy. This paper focuses on the relation between leprosy policy and
      medicine, and from this, I make clear the similarity, or peculiarity of the
      isolation policy between Japan and the vest of the world, and clarify the factors
      of progress of the absolute isolation policy. The processes are historical and
      medical historical the verification of the relation between the formation of the
      national medicine and the progress of the isolation policy of Meiji Era, the
      proposal of the isolation policy by Dr. Keizo Dohi, Dr. Shibasaburo Kitasato, and
      Dr. Masatsugu Yamane, and the application by Dr. Kensuke Mitsuda, the decision to
      enact this policy and its support by the Health and Medical Bureau and the
      Department of the Interior, as well as many factors.

PMID- 16562496
TI  - [Future strategies for global leprosy control].
AB  - WHO has recently proposed a 5-year strategy plan for leprosy control beginning
      from 2006 to 2010. Even though currently there are still nine countries which
      have yet to achieve the goal of eliminating leprosy, it is considered to be
      accomplished in the near future. It is expected that the number of newly detected
      cases are expected to decline in the future by early detection, accurate
      diagnosis, early treatment, preventing disabilities and by further continuing the
      leprosy control activities.

PMID- 16562497
TI  - [Situation of global leprosy].
AB  - The epidemiological situation of leprosy is reported by the health division of
      each country to WHO. The reported data is collected by WHO and is immediately run
      on the Weekly Epidemiological Record. On this latest edition, data from the
      beginning of 2005 was reported. According to this edition, the importance of the
      fact that nine countries in the world has yet to achieve the WHO goal of
      eliminating leprosy, early detection and constantly providing drugs free of
      charge, and continuing to carry out the leprosy control activities within the
      general health services.

PMID- 16562498
TI  - Leprosy in Mexico.
AB  - The time of the settlement of leprosy in Mexico is uncertain, however recent
      studies pointed out that leprosy was probably brought by Asian's migration at
      about 12,000 years ago and not by the Europeans conquerors during XVI and XVII
      centuries. Registration of leprosy has been done since the colonial era and the
      disease was considered as a public health problem until the year 2004 in Mexico
      when the incidence was achieved to be less than 1 per 10,000 as defined by the
      world health organization (WHO). Although the national epidemiological parameters
      like prevalence show the leprosy are controlled well, there are still 49
      prefectures with higher prevalence in Mexico. In addition, the incidence in last
      10 years has not been stably reduced, in other words the infection cycle has not
      been interrupted. Therefore, it is necessary to keep the careful epidemiological
      monitoring, and to increase the search and follow-up of new cases and their
      contacts in order to eliminate leprosy in this country.

PMID- 16562499
TI  - [Electrical propagation in cardiac muscle and its modulation by potassium
      channels and potassium channel modulators].

PMID- 16562500
TI  - The change of the split renal function before and after a nephrectomy using Tc
      mercaptoacetyltriglycine (MAG3).
AB  - OBJECTIVE: We examined the change in the renal function in the normal side kidney
      before and after a nephrectomy, by means of a newly developed diuretic renography
      technique utilizing Tc 99m-mercaptoacetyltriglycine (MAG3). MATERIALS AND
      METHODS: Forty patients who underwent a nephrectomy were evaluated using MAG3
      diuretic renography. We measured the effective renal plasma flow (ERPF) and Tmax
      time before and after a nephrectomy. The effects of the patient age and the
      preoperative ERPF of ill side kidney on the post operative ERPF were then
      assessed statistically. RESULTS: The ERPF increased by an average of 44.8 ml/min
      at 2 weeks after a nephrectomy, but it decreased by an average of 24.3 ml/min at
      3 months after a nephrectomy. The Tmax time decreased by an average of 0.58 min
      at 2 weeks, but thereafter increased by an average of 0.58 min at 3 months after
      a nephrectomy. The correlation coefficient between the rate of increase in the
      ERPF and the patient age was 0.197. CONCLUSIONS: The rise of renal function in
      terms of ERPF and the Tmax time was observed at 2 weeks post-nephrectomy.
      However, this effect disappeared at 3 months post-nephrectomy. These data
      demonstrated that the rise in the renal function of the normal-side kidney in
      such patients was only temporary.

PMID- 16562501
TI  - A machine vision system with CCD cameras for patient positioning in radiotherapy:
      a preliminary report.
AB  - PURPOSE: To determine positioning accuracy of a machine vision system in
      radiotherapy. MATERIALS AND METHODS: The machine vision system was composed of
      640 x 480 pixel CCD cameras and computerized control systems. For image
      acquisition, the phantom was set up for the reference position and a single CCD
      camera was positioned 1.5 m from the isocenter. The image data of the fiducial
      marker with 1.5 mm lead pellet on the lateral surface of the phantom was captured
      onto the CCD, and then the position of the marker was accurately calculated. The
      phantom was moved 0.25, 0.50, 0.75, 1.00, 2.00, and 3.00 mm from the reference
      position, using a micrometer head. The position of the fiducial marker was
      analyzed using a kilo-voltage fluoroscopic imaging system and a machine vision
      system. RESULTS: Using fluoroscopic images, the discrepancy between the actual
      movement of the phantom by micrometer heads and the measurement was found to be
      0.12 +/- 0.05 mm (mean +/- standard deviation). In contrast, the detection of the
      movement by the machine vision system coincided with the discrepancy of 0.0067 +/
      0.0048 mm. CONCLUSION: This study suggests that the machine vision system can be
      used to measure small changes in patient position with a resolution of less than
      0.1 mm.

PMID- 16562502
TI  - [Image analysis of retinal nerve fiber layer].

PMID- 16562503
TI  - [Evaluation of the effect of aging on retinal nerve fiber thickness of normal
      Japanese measured by optical coherence tomography].
AB  - PURPOSE: To determine the normal retinal nerve fiber layer (RNFL) thickness as
      measured by optical coherence tomography (OCT), and to evaluate the relationship
      between RNFL thickness in healthy Japanese and their age. METHODS: One hundred
      healthy Japanese subjects were enrolled. The RNFL thickness was measured using
      OCT with three circle scans 3.4 mm in diameter. RESULT: The mean thickness of
      RNFL measured around the optic disc was 108 +/- 13.5 microm. The average RNFL
      thickness in the temporal, superior, nasal, and inferior quadrants was 80 +/-
      15.9 microm, 132 +/- 20.7 microm, 80 +/- 17.0 microm and 136 +/- 20.0 microm,
      respectively. There was a statistically significant negative correlation between
      age and the average RNFL thickness around the disc, and in the temporal quadrant.
      Using 30-degree segments, there were negative correlations between age and RNFL
      thickness in temporal-superior and temporal-inferior segments. CONCLUSION: RNFL
      thickness in healthy Japanese subjects measured by OCT decreased with age in the
      temporal-superior and temporal-inferior quadrants. Our results suggested that the
      regional and age-related differences in RNFL thickness must be taken into
      consideration before making clinical interpretations of the RNFL abnormalities
      measured by OCT.

PMID- 16562504
TI  - [Degree of degraded proteoglycan in human vitreous and the influence of
      peroxidation].
AB  - PURPOSE: The degradation of hyaluronic acid induced by reactive oxygen species
      has been reported in vitro as a cause of vitreous liquefaction. In this study on
      in vivo human vitreous liquefaction, we examined the degree of degraded
      proteoglycan (PG) in human vitreous and the influence of peroxidation. SUBJECTS
      AND METHODS: In this study we examined the vitreous of 5 eyes with diabetic
      retinopathy, 12 eyes with retinal detachment, 2 eyes with retinal vein occlusion,
      and one eye with macular hole. The degree of degraded PG was determined by
      cellulose acetate membrane electrophoresis. To evaluate the influence of
      oxidation, copper ions, iron ions, hydrogen peroxide, lipid peroxide, L-ascorbic
      acid concentrations, and superoxide scavenging activity were measured. RESULTS:
      The electrophoretic patterns of PG were classified into the origin type (non
      fragmented PG) in which only the origin was stained, and the mobile type
      (fragmented PG) showed other patterns. In the mobile type, the copper ion and
      hydrogen peroxide concentrations were higher, and the lipid peroxide
      concentrations were significantly higher, while the superoxide scavenging
      activity was lower. CONCLUSION: These results indicated that the degradation of
      PG and dissociation of glycosaminoglycan in human vitreous were associated with
      peroxidation.

PMID- 16562505
TI  - [Correlations among GDx-variable corneal compension, optical coherence
      tomography, and Heidelberg retina tomograph and relationships between these
      structural parameters and visual field indices].
AB  - PURPOSE: In glaucoma patients, to compare the correlations among parameters
      measured by Heidelberg Retina Tomography(HRT) and retinal nerve fiber layer
      thickness (RNFLT) measured by GDx-variable corneal compensation (GDx-VCC) and
      optical coherence tomography (OCT), and to assess the relationship among these
      structural parameters, and visual field damage. METHODS: A unilateral eye of 110
      patients with open-angle glaucoma were included in this study. Each individual
      was analyzed by HRT (version 3.04), GDx-VCC (version 5.3.2), and OCT-1 (version
      A6 X1). The correlations among these parameters regarding global area, superior
      sector, and inferior sector were obtained from the 3 instruments and compared.
      The correlations among the mean deviation (MD) in the Humphrey field analysis and
      the parameters in global area from the 3 instruments were calculated. RESULTS:
      The MD showed quadratic regressions to each global parameter (GDx-VCC; 0.625
      (nerve fiber indicator): OCT 0.616 (average RNFLT); HRT, 0.501 (rim area)). Most
      parameters in OCT and GDx-VCC had highly significant correlations. The rim area
      showed the highest correlation in each sector to RNFLT with GDx-VCC or OCT among
      HRT parameters. CONCLUSIONS: These structural parameters derived from GDx-VCC,
      OCT and HRT analyses had bilinear correlation to the MD. Retinal nerve fiber loss
      detected on GDx-VCC and OCT correlated linearly with the neuroretinal rim area
      measured by HRT. These instruments may be useful in monitoring structural changes
      in glaucoma.

PMID- 16562506
TI  - [Case of recurrent fungal endophthalmitis with suspected Munchausen syndrome].
AB  - PURPOSE: To report recurrent fungal endophthalmitis which developed after
      endogenous fungal endophthalmitis. The patient was suspected to be suffering from
      Munchausen syndrome. CASE: A 44-year-old woman contracted endogenous fungal
      endophthalmitis in her right eye in October 2000. After the endophthalmitis was
      healed by vitrectomy, corneal ulcer and endophthalmitis repeatedly occurred in
      the eye from an unknown cause. The patient finally lost the sight of her right
      eye. The corneal ulcer and endophthalmitis resulted from self-injury for which we
      found material evidence in the course of the treatment. Munchausen's syndrome was
      suspected but the patient persistently refused to see a psychiatrist. CONCLUSION:
      We must be prepared to provide mental and psychiatric care in addition to
      ophthalmological treatment for such a case.

PMID- 16562507
TI  - [Case of herpes zoster ophthalmicus with abducent palsy: the cause and magnetic
      resonance imaging findings].
AB  - PURPOSE: To report the cause and magnetic resonance imaging (MRI) findings in a
      case of abducent palsy following herpes zoster ophthalmicus. CASE: A 76-year-old
      man presented with acute onset of pain, a vesicular cutaneous eruption and herpes
      zoster ophthalmicus on the right side. He developed complete abducent palsy on
      the right side two weeks after onset. MRI with gadolinium enhancement showed
      Meckel's sinus, which contains the trigeminal ganglion, and the abducent nerve on
      the right side. The patient was treated with intravenous acyclovir and
      methylprednisolone. The abnormal enhancement shown on MRI vanished immediately
      and the ophthalmoplegia resolved significantly. CONCLUSION: This is the first
      reported case where an affected cranial nerve was detected next to the
      inflammatory cavernous sinus in ophthalmoplegia following herpes zoster
      ophthalmicus. These MRI findings showed that this ophthlamoplegia was induced by
      direct viral invasion or extension of inflammation to the ipsilateral cranial
      nerve. Further studies need to be performed to clarify the role of specific
      antiviral therapy or anti-inflammatory agents in treating this complication of
      herpes zoster.

PMID- 16562508
TI  - [Bacterial endopathalmitis caused by B streptococcus endocarditis].
AB  - BACKGROUND: Bacterial endophthalmitis is often caused by a shift in the primary
      focus of infection in the patient's body. It is a high risk disease that can
      cause the loss of sight. Bacterial endophthalmitis with infectious endocarditis
      is very rare in Japan. CASE: A fifty-three-year-old woman visited our clinic
      complaining of pain, fever, and visual impairment in her left eye. OBSERVATIONS:
      The patient's left eye was blind, and showed hapopyon in the anterior chamber.
      She was admitted to our hospital with a diagnosis of endophthalmitis. Medical
      treatment with antibiotics was carried out, but the inflammation in her left eye
      increased. Her left eye was enucleated, and group B Streptococcus was found in
      the vitreous specimen. Echocardiography demonstrated vegetation of the posterior
      mitral valve. The diagnosis was made of endophthalmitis due to infectious
      endocarditis. CONCLUSION: We report an endophthalmitis patient with infectious
      endocarditis caused by group B streptococcus, based on histopathological
      findings. This is the first such case reported in Japan.

PMID- 16562509
TI  - [Ultra-late phase of indocyanine green angiography in a case with metastatic
      choroidal tumor].
AB  - PURPOSE: To report a case with metastatic choroidal tumor evaluated with ultra
      late phase of indocyanine green (ICG) angiography. CASES: A 43-year-old woman had
      metastatic choroidal tumor originating from the thymus with an associated serous
      retinal detachment. ICG video-angiography demonstrated the tumor as
      hypofluorescent during the arterio-venous phase and hyperfluorescent during the
      conventional late phase (about 30 minutes after dye injection), and in the ultra
      late phase (24 hours after dye injection). The original and metastatic tumors
      were treated by radiotherapy, resulting in flattening of the choroidal tumor and
      resolution of the serous retinal detachment. After the treatment, ICG angiography
      showed decay of ICG fluorescence and no apparent late accumulation of residual
      ICG in the tumor. CONCLUSION: In a case with metastatic choroidal tumor, ICG dye
      accumulated in the tumor tissue before the treatment, but it decreased after
      treatment. This finding suggested that dye accumulation may be correlated with
      the tumor activity and requires a further study, enrolling patients with
      metastatic choroidal tumor for ICG angiographic evaluation.

PMID- 16562510
TI  - [Melanoma-associated retinopathy with unknown primary site in a Japanese woman].
AB  - BACKGROUND: We report the clinical features of the first case of a Japanese
      person with melanoma-associated retinopathy. CASE: A 44-year-old woman complained
      of photopsia and blurred vision in her right eye, and was treated with steroids
      for uveitis by an ophthalmologist. She was referred to our hospital for further
      examination. After one month of treatment, she still complained of photopsia in
      her right eye. The best corrected visual acuity in the right eye was 0.8 and
      these was sensitivity loss in the central visual field test. Ophthalmoscopy and
      fluorescein angiography showed some retinal vasculitis in the right eye. A full
      field electroretinogram demonstrated a negative-type electroretinogram (ERG)
      waveform with attenuation of the b-wave amplitude in the right eye. A dark
      adaptation test revealed sensitivity loss of the rods. The lymph nodes on the
      right side of her neck were examined and the diagnosis was made of metastic
      cutaneous melanoma with unknown primary site; her visual dysfunction was
      diagnosed as melanoma-associated retinopathy. The retinal inflammation improved
      after steroid treatment, but her visual dysfunction remained. Chemotherapy and an
      immunotherapy regimen was begun, but 36 months later she died of metastatic
      melanoma in the lungs. CONCLUSIONS: A woman treated for uveitis without any prior
      systemic and ocular diseases was diagnosed with melanoma-associated retinopathy
      and metastatic melanoma in the cervical lymph nodes of unknown primary origin.
      The first ocular symptoms were photopsia and blurred vision, not night blindness.
      ERG was useful for diagnosing this rare ocular condition in an early stage.

PMID- 16562511
TI  - [Optical coherence tomographic findings of the retinal pigment epithelium tear in
      macular area preserving good visual acuity].
AB  - PURPOSE: It has been reported that the visual outcome of retinal pigment
      epithelial tear (RPE tear) in the fovea is worse than that of RPE tear sparing
      the fovea. We report optical coherence tomography (OCT) findings of 3 cases with
      RPE tear in the fovea who preserved good visual acuity. PATIENTS: All patients
      had serous retinal pigment epithelial detachment involving the macula. The RPE
      was torn and rolled RPE was observed in the fovea. In OCT findings, a fovea was
      observed on the RPE flap, and visual acuity was preserved after RPE tear repair.
      CONCLUSION: We considered that preservation of good visual acuity was due to the
      presence of a fovea on the RPE flap. We could precisely analyze the location of
      the fovea and RPE tear using OCT.

PMID- 16562512
TI  - [Case of spontaneous regression of intraocular lymphoma demonstrated by
      subretinal biopsy].
AB  - PURPOSE: To report a case of intraocular lymphoma suspected of spontaneous
      regression based on ocular fundus findings, subretinal biopsy, and observation of
      clinical course. CASE: A 64-year-old woman presented at our clinic with multiple
      yellowish-white patchy lesions in the left fundus and focal atrophy of the
      retinal pigment epithelium in the right fundus. No inflammatory infiltrates were
      observed in either eye. Intraocular lymphoma was suspected based on the clinical
      manifestations including fluorescein angiography and optical coherence
      tomography. Vitrectomy and subretinal biopsy were subsequently performed for
      diagnostic purposes. Histological examination showed that the subretinal lesion
      was composed mostly of necrotic tissue derived from the lymphoid corpuscle and
      that there was no cellular component except the retinal pigment epithelium.
      Interleukin-10 in the vitreous humor was low at 9 pg/ml. No serious postoperative
      complications were observed after surgery and the residual retinal lesions
      gradually regressed spontaneously. Laboratory data and whole body evaluation
      including the central nervous system (CNS) showed no remarkable findings for 1
      year after surgery. CONCLUSIONS: It is suggested that the present case was an
      intraocular lymphoma which regressed spontaneously. However, careful follow-up
      including the possible occurrence of CNS lesions is required in such cases.

PMID- 16562513
TI  - [Epidemiological study of schizophrenia on the Island of Tsushima in Nagasaki
      Prefecture].
AB  - The epidemiology of schizophrenia has been studied with regard to the incidence,
      prevalence, and morbid risk, and there have been comprehensive reviews. However,
      the incidence and prevalence have not been analyzed simultaneously in many
      studies. In the present study, which was performed on a remote island, the number
      of patients could be determined, and they could be followed up by the same
      observer. This permitted us to conduct comprehensive epidemiological research
      while providing local mental health care. The subjects were patients diagnosed
      with schizophrenia according to the DSM-III-R in Tsushima, Nagasaki Prefecture,
      between April 1, 1988 and March 31, 1996. The incidence of schizophrenia was 2.3
      (2.5 in males, 2.1 in females) per 10,000 people of the population, and the age
      adjusted incidence was 2.4. Its prevalence was 5.8 (6.1 in males, 5.7 in females)
      per 1,000 people of the population, and the age adjusted prevalence was 6.2. In
      both sexes, the number of patients and the prevalence increased annually. The
      morbid risk was 0.95% (1. 01% in males, 0.89% in females) by the direct method
      (calculated from the incidence) and 0.85% (0.90% in males, 0.81% in females) by
      the indirect method (calculated from the prevalence), showing similarity. These
      incidence, prevalence, and morbid risk results did not markedly differ from the
      values reported to date. It is important to establish preventive measures for
      schizophrenia on the basis of the basic data obtained in this study, and to
      serially evaluate changes in epidemiological parameters of schizophrenia after
      their application. Furthermore, by comparing these epidemiological findings with
      those of other mental disorders and other regions, methods are expected to be
      utilized comprehensively for local mental health care.

PMID- 16562514
TI  - [Kumagusu Minakata with temporal lobe epilepsy: a pathographic study].
AB  - Kumagusu Minakata (1867-1941), a Japanese genius devoted to natural history and
      folklore, is famous for his immense range of works (including 50 monographs in
      'Nature') and his discovery of several varieties of mycetozoa. His diary and the
      observations of other persons reveal that he was affected by several grand mal
      epileptic seizures, and he complained himself of frequent deja vu experiences
      which he called promnesia according to Myers. Promnesia means, for example, "I
      have lived through all this before, and I know what will happen this next
      minute." Minakata also had this rare type of aural sign. MRI analysis of his
      postmortem brain found evidence of right hippocampal atrophy. This result showed
      that he had temporal lobe epilepsy with focus of the right side, and this
      coincides with his deja vu experiences which were the aura of the loss of
      consciousness. However, he did not notice that these were aural signs, and he
      also complained of memory disturbances due to frequent deja vu. His behavioral
      characteristics were peculiar, and those of Dostoyevsky who also had temporal
      lobe epilepsy were similar. Temporal lobe epilepsies may influence behavioral
      patterns which control the emotions. As a positive point, some patients with
      temporal lobe epilepsy can exhibit their primordial mental actions and perform
      persistent works.

PMID- 16562515
TI  - [Narrative-based medicine and clinical knowledge].
AB  - Narrative Based Medicine (NBM) can be defined as follows; a) It views the
      patient's illness as an unfolding story within the wider story of the patient's
      life and life-world; b) It acknowledges the patient as the narrator of the story
      and the subject of the tale; c) It recognizes that all medical theories,
      hypothesis and pathophysiologies as socially constructed narratives and accepts
      the coexistence of multiple different narratives; d) It regards the emergence of
      new stories from dialogue and discourse between patients and healthcare
      professionals as part of the treatment. Because psychiatry is the only area of
      specialist medicine where talking and listening are explicitly understood to be
      therapeutic, NBM can be adopted an effective perspective and method in
      psychiatry.

PMID- 16562516
TI  - Benchmarking physician performance, Part 1.
AB  - The performance of 16 primary care physicians in the same medical specialty and
      university clinic is compared using data envelopment analysis (DEA) efficiency
      scores. DEA is capable of modeling multiple criteria and automatically determines
      the relative weights of each performance measure. In this research, the
      performance measures include physician work relative value units (RVUs) as an
      input variable and patient satisfaction and total billable charges as the two
      output variables. The results provide insights into: 1. Who are the best
      performing physicians? 2. Who are the underperforming physicians? 3. How can
      underperforming physicians improve? 4. What are the underperformers' performance
      targets? 5. How do you deal with full- and part-time physicians in a university
      setting? This research also provides a preliminary framework for how work
      measurement and DEA analysis can be used as a basis for a medical team or
      physician compensation system.

PMID- 16562517
TI  - 10 ways to give your office a face-lift.
AB  - Many medical practices have antiquated offices where patients, staff and
      physicians are bored with the surroundings. There are ideas that can be easily
      implemented to make your practice attractive and enjoyable, as well as effective.
      This article shows you how to review the physical environment of your practice
      and then find an architect who specializes in designing medical practices.

PMID- 16562518
TI  - Minimizing medical litigation, Part 1.
AB  - The global rise in medical litigation has led to defensive medical practices and
      rising malpractice insurance premiums. There is a need to review all possible
      factors influencing litigiousness of the society and to develop strategies to
      control such factors. Some of the contributory causes of rising litigiousness
      include higher patients' expectations, poor provider-patient communication, and
      adversarial legalism of the society. A good combination of system, professional,
      and legislative strategies may keep medical litigation in check. Part 2 of this
      article will address the development of a dispute resolution framework.

PMID- 16562519
TI  - 25 ways your employees can be goodwill ambassadors for your medical practice.
AB  - Most medical practice employees want their patients' experiences to be very
      positive. This article suggests 25 specific, easy, and no- or low-cost strategies
      every staff member can use to roll out the red carpet for patients. It provides
      several easy-to-implement techniques for remembering and using personal
      information about patients to demonstrate that you and your staff care about
      them. This article also suggests a number of finesse strategies that will make
      every office visitor feel like a VIP. It offers specific do's and don'ts about
      being courteous to patients. It also offers several tips your staff can use to
      become goodwill ambassadors for your practice in your community and for going the
      extra mile for your patients. Finally, this article offers a step-by-step
      procedure your staff can use to shake hands professionally with every one of your
      patients.

PMID- 16562520
TI  - E/M documentation pitfalls and audit advice.
AB  - This article examines some of the potential problems inherent in the 1995 and
      1997 Federal Documentation Guidelines and goes on to give some broad advice
      regarding documentation of evaluation and management (E/M) services. One small
      area covered by the guidelines, the history of present illness (HPI), is given
      some attention as an example of the variability of the guidelines. The use of
      templates and electronic medical records (EMR) is also addressed in terms of how
      auditors and regulators would like to see these tools used. A section is devoted
      to the most important elements of medical record documentation from an auditing
      perspective. A do's and don'ts section covers common areas of chart deficiencies
      and focus.

PMID- 16562521
TI  - Physician ancillary services: fad or fashion? Part 2.
AB  - Ancillary services are quite fashionable in today's medical practice, but perhaps
      you've wondered if they were only a fad. If you're considering adding services to
      increase your revenue, you're not too late; this trend seems here to stay. Doing
      your homework and due diligence is key to the success of your ancillary business.
      Before introducing a service into your practice or investing in an ancillary
      venture, make sure that you get off on sound footing. Major investments call for
      experienced consulting and tapping into financial, operational, and legal
      specialists to address specific needs. Part 1 defined ancillary services and
      addressed performing the feasibility study and writing the business plan. In this
      second part, legal and regulatory issues, financing arrangements, opening, and
      operational and ongoing management elements critical to success are all explored.

PMID- 16562522
TI  - What happens when the harassment is personal?
AB  - The medical field has long endured the destructive forces of personal harassment
      in work environments. Personal harassment, often called workplace bullying, has
      historically been kept quiet. The targets of personal harassment suffered in
      silence. Many of the targets either left the organization or became passive
      aggressive members of the work team. Personal harassment is no longer tucked away
      in the shadows, however. This issue is now being cited as a major cause of low
      morale, high employee turnover, and increased workplace violence. The intent of
      this article is to provide an awareness of personal harassment and how it has had
      a catastrophic impact on the medical field. Awareness of this issue is the first
      step toward its prevention. Medical practitioners, leaders, and employees must
      commit to addressing this issue before it can adversely impact their
      organizations.

PMID- 16562523
TI  - Keep your staff connected.

PMID- 16562524
TI  - Performance appraisal: helpful hints for the busy medical practice manager.
AB  - This article describes the performance appraisal process in terms of its three
      fundamental steps. defining job performance, measuring actual job performance,
      and providing job performance feedback. Given that most practice managers wear
      many hats and do not have extensive experience or staff support in human
      resources, the purpose of this article is to provide these busy individuals with
      useful, practical suggestions that should enhance the effectiveness of the
      performance appraisal process for nonphysician employees within the medical
      practice setting. Performance appraisal should be a priority for all practice
      managers, as the performance of individual employees represents the key to long
      term success for any medical practice.

PMID- 16562525
TI  - Rural healthcare: how to recruit and retain health professionals.
AB  - A major challenge for healthcare in the United States is recruiting and retaining
      health professionals in rural areas of the country. There is a significant
      shortage of physicians and other health professionals in many of these areas.
      This article outlines some of the factors that go into recruiting health
      professionals to practice in rural communities, and what factors are influential
      in making sure they remain in service to those communities.

PMID- 16562526
TI  - Beyond the professional fee, Part 1: Basic legal issues for physicians investing
      in the technical side of healthcare services.
AB  - As reimbursement for professional services shrinks in comparison with physicians'
      educational debt and practice expenses, physicians are looking for additional
      sources of revenue to supplement their practice income. A natural option to
      consider is investment in healthcare entities or equipment in order to share in
      the technical fees generated by such entities or equipment.

PMID- 16562527
TI  - Deferred compensation: what physicians need to know about IRC 409A.
AB  - The American Jobs Creation Act of 2004 added Internal Revenue Code (IRC) Section
      409A, which makes changes to nonqualified deferred compensation plans. Physician
      practice groups can take steps to avoid the risk of penalty from noncompliance.
      Precision and caution in addressing deferred compensation arrangements are
      especially important now since the IRS has targeted non-qualified deferred
      compensation plans as the number-one executive compensation compliance issue in
      its ongoing audit initiative.

PMID- 16562528
TI  - Trends in the consumer price index.

PMID- 16562529
TI  - The myriad pieces of facility development, Part 3.
AB  - Medical practices often find that they have outgrown their office space and
      cannot relocate within the same building or in the vicinity of their current
      location. They are confronted with the need to develop and build a new facility.
      Parts 1 and 2 of this series helped you conceive your new office and get it
      designed and ready for construction. Now it is time to build.

PMID- 16562530
TI  - Deducting your way to a lower tax bill.

PMID- 16562531
TI  - Healthcare costs continue to rise.

PMID- 16562532
TI  - [Whooping cough: a diagnosis one shouldn't forget].
AB  - Reports of whooping cough, due to Bordetella pertussis, have been increasing
      worldwide for the last two decades in all age groups. Infants are especially at
      risk for severe disease, but older children and adolescents can have a great
      disease burden as well. Diagnosing pertussis is difficult due to atypical
      symptoms, and frequent lack of laboratory confirmation. This article reviews the
      reasons for epidemiologic changes, clinical manifestations, diagnostic tools,
      treatment and prevention strategies, especially vaccination which will most
      certainly focus in the future on decreasing susceptible pools by immunizing
      adolescents and young adults. This strategy would not only protect these
      individuals from whooping cough, but most importantly protect, by herd immunity,
      the infants too young to be (fully) immunized.

PMID- 16562533
TI  - [Chronic otitis media in children].
AB  - Otitis media with effusion is the main chronic otitis in children. It is very
      common under 5 years of age. It is often asymptomatic or is revealed by a hearing
      loss, delaying language development or causing behaviour troubles or balance
      troubles. Repeated acute otitis media may also occur. Tympanic membrane aspect is
      variable: pneumotoscopy and tympanometry are valuable diagnostic tools. Long term
      consequences on child development and possible scarring of the eardrum and the
      ossicles must be kept in mind. Treatment consists in watchful waiting during 3
      months, then adenoidectomy and middle ear drainage. There is no efficient drug.
      Other chronic middle ear infections may cause serious hearing and infectious
      complications and require surgical treatment.

PMID- 16562534
TI  - [How to deal with gastroesophageal reflux in childhood].
AB  - Gastroesophageal reflux is frequent source of consultation at the paediatrician's
      room, although most GER resolve spontaneously in infancy. In most cases, after a
      thorough anamnesis and a full physical examination prokinetic and anti-acid
      medications are started, as well as postural change, without the assistance of a
      specialist. When reflux is complicated by either oesophagitis, respiratory
      symptoms, failure to thrive or when the above treatment fail, further
      investigations need to be undertaken. Their option will depend on the clinical
      presentation. Rarely GER will lead to surgery.

PMID- 16562535
TI  - [Short stature].
AB  - Careful clinical assessment and a limited number of laboratory investigations
      usually allow distinguishing pathologic short stature from a great number of
      children presenting with constitutional or familial short stature. Chronic
      digestive and renal problems have to be ruled out. Growth hormone deficiency may
      be difficult to diagnose. Turner syndrome has to be ruled out in any girl with so
      far unexplained short stature. More difficult is the clinical diagnostic
      orientation to rare genetic disorders, such as skeletal dysplasias, genetic
      syndromes and inborn errors of metabolism. Medical history, clinical assessment
      and oriented investigations allow to isolate difficult cases and to refer them to
      specialists for specific therapy and/or genetic counselling.

PMID- 16562536
TI  - [Gifted children in difficulty: from attention deficit hyperactivity disorder to
      depression and school failure].
AB  - We became interested in gifted children with difficulties based on the number of
      children who were addressed to our outpatient units for behavioral problems such
      as Attention Deficit Hyperactivity Disorder, scholastic problems or symptoms of
      depression, and for whom we identified a high intellectual potential. This
      article treats in particular Attention Deficit Hyperactivity Disorder (ADHD)
      which is observed for certain gifted children and can cover a depression and lead
      to school failure. How can ADHD in gifted children be interpreted? Based on our
      clinical experience and the literature, we propose that this disorder stem from
      need for external and internal stimulation. Several hypotheses concerning this
      idea will be then discussed, notably concerning their therapeutic implications.

PMID- 16562537
TI  - [An observatory of child abuse and neglect: an interactive way to look at this
      issue].
AB  - Since the second part of the 20th century, professionals from diverse backgrounds
      have been looking at child abuse end neglect issues without a real common
      approach and understanding. The objective of the Observatory is to allow these
      professionals, whatever their research or practice background is, to confront
      their views and ideas within a constructive interdisciplinary framework, aiming
      at better serving victims, families and perpetrators needs.

PMID- 16562538
TI  - [Partial Horner's syndrome and facial pain: a diagnosis one should not miss].
AB  - Internal carotid artery dissection typically manifests as an unilateral facial or
      latero-cervical pain, is often accompanied by an oculosympathetic palsy (myosis
      and palpebral ptosis) and may be followed by cerebral or retinal ischemia.
      Deficits of the IXth to XIIth cranial nerves or a pulsatile tinnitus have been
      described. These symptoms challenge our clinical skills and call for an early
      diagnosis in order to prevent ischemic complications. Both helical computed
      tomographic angiography and transcranial ultrasonography coupled with Doppler
      flow colour are excellent first-line imaging techniques. Conventional angiography
      has been replaced by magnetic resonance techniques as gold standard. In this
      article, we describe the case of a patient evaluated at our outpatient clinic and
      review briefly the literature on this topic.

PMID- 16562539
TI  - [Arterial hypertension: details concerning the "update" emission].

PMID- 16562540
TI  - [Defensive medicine practice in the United States. When Switzerland?].

PMID- 16562541
TI  - [Retroviruses and opportunistic diseases: the catch of intermittent treatments?].

PMID- 16562542
TI  - [French biologists authorized to carry out research on human embryos (2)].

PMID- 16562543
TI  - [Sicilian swans and the black continent].

PMID- 16562544
TI  - [A policy without a project].

PMID- 16562547
TI  - [Inhalation therapy].

PMID- 16562548
TI  - [Vaccination against tuberculosis].

PMID- 16562549
TI  - [Enterprise project, management tool: the case of the General Health].

PMID- 16562550
TI  - [Inserting and maintaining a peripheral catheter access].

PMID- 16562551
TI  - [Rosiglitazone].

PMID- 16562552
TI  - [Creating an artificial contrast to explore a cavity].

PMID- 16562553
TI  - [Contraception 2005: new methods and a different approach].

PMID- 16562554
TI  - Hospitals must bare it all under new price transparency initiatives.

PMID- 16562555
TI  - Medicare overpaid dollar 110 million for part B drugs.

PMID- 16562556
TI  - HHAs bristle at 2007 rate freeze proposal.

PMID- 16562557
TI  - Class III DME could lose out on payment update.

PMID- 16562559
TI  - Preferred overall loudness. I: Sound field presentation in the laboratory.
AB  - This study questions the basic assumption that prescriptive methods for
      nonlinear, wide dynamic range compression (WDRC) hearing aids should restore
      overall loudness to normal. Fifteen normal-hearing listeners and twenty-four
      hearing-impaired listeners (with mild to moderate hearing loss, twelve with and
      twelve without hearing aid experience) participated in laboratory tests. The
      participants first watched and listened to video sequences and rated how loud and
      how interesting the situations were. For the hearing-impaired participants, gain
      was applied according to the NAL-NL1 prescription. Despite the fact that the NAL
      NL1 prescription led to less than normal overall calculated loudness, according
      to the loudness model of Moore and Glasberg (1997), the hearing-impaired
      participants rated loudness higher than the normal-hearing participants. The
      participants then adjusted a volume control to preferred overall loudness. Both
      normal-hearing and hearing-impaired participants preferred less than normal
      overall calculated loudness. The results from the two groups of hearing-impaired
      listeners did not differ significantly.

PMID- 16562560
TI  - Preferred overall loudness. II: Listening through hearing aids in field and
      laboratory tests.
AB  - In a laboratory study, we found that normal-hearing and hearing-impaired
      listeners preferred less than normal overall calculated loudness (according to a
      loudness model of Moore & Glasberg, 1997). The current study verified those
      results using a research hearing aid. Fifteen hearing-impaired and eight normal
      hearing participants used the hearing aid in the field and adjusted a volume
      control to give preferred loudness. The hearing aid logged the preferred volume
      control setting and the calculated loudness at that setting. The hearing-impaired
      participants preferred, in median, loudness levels of -14 phon re normal for
      input levels from 50 to 89 dB SPL. The normal-hearing participants preferred
      close to normal overall loudness. In subsequent laboratory tests, using the same
      hearing aid, both hearing-impaired and normal-hearing listeners preferred less
      than normal overall calculated loudness, and larger reductions for higher input
      levels In summary, the hearing-impaired listeners preferred less than normal
      overall calculated loudness, whereas the results for the normal-hearing listeners
      were inconclusive.

PMID- 16562561
TI  - The role of silent intervals for sentence intelligibility in fluctuating noise in
      hearing-impaired listeners.
AB  - Fluctuating interfering noises are highly suitable for speech audiometry because
      of the large inter-individual variability in intelligibility results. This study
      explores the maximum duration of silent intervals in the masker as an important
      factor underlying sentence intelligibility in fluctuating noise. Three versions
      of speech-simulating fluctuating interfering noises based on the icra noises
      (Dreschler et al, 2001) were explored: The original noise which simulates one
      interfering speaker and contains pause durations up to two seconds, as well as
      two modified versions with pause durations limited to 250 ms and 62.5 ms,
      respectively. In addition, a stationary speech-shaped noise was used. Test-retest
      reliability as well as speech reception threshold (SRT) and speech
      intelligibility function slope were determined with hearing-impaired subjects.
      All fluctuating noises differentiated very well between subjects. Partial rank
      correlation analysis showed that SRTs in fluctuating noise with longest maximum
      pause durations mostly depended on SRTs in quiet. SRTs in fluctuating noises with
      smaller maximum pause durations correlated both with SRTs in quiet and in
      stationary noise.

PMID- 16562562
TI  - Distortion product otoacoustic emissions in patients with King-Kopetzky syndrome.
AB  - In the present study, mild impairment of cochlear function in patients with King
      Kopetzky syndrome was investigated using DPOAEs. A significant decrease in DPOAE
      levels in both ears was found in patients with King-Kopetzky syndrome compared
      with the controls after considering the thresholds as a co-variable. It is
      noteworthy that the global mean levels of DPOAEs were still significantly greater
      in controls than in patients with matched thresholds. Further frequency analyses
      showed a significant decrease in DPOAE levels over the mid- and high-frequency
      range in patients with better hearing thresholds when compared with those in the
      control group. Moreover, significantly smaller DPOAEs were found in the ears of
      patients with King-Kopetzky syndrome and without SOAEs, than in such ears of
      control subjects after considering the thresholds as a co-variable. However, when
      SOAEs were present there was no difference. Decreases in DPOAE level appear to
      represent evidence of minor cochlear pathology, and provide a pathological basis
      for the difficulty of hearing speech in the presence of background noise, which
      characterizes King-Kopetzky syndrome.

PMID- 16562563
TI  - Frequency-specific objective audiometry: tone-evoked brainstem responses and
      steady-state responses to 40 Hz and 90 Hz amplitude modulated stimuli.
AB  - Tone-evoked Auditory Brainstem Responses (tone-burst ABRs) and Auditory Steady
      State Responses (ASSRs) with 40 or 90 Hz amplitude modulation (AM) were compared,
      using the same equipment and recording parameters, to determine which of these
      three methods most accurately approached the behavioural hearing thresholds in
      response to 500 Hz and 2000 Hz stimuli in eleven awake adults with normal
      hearing. Estimates of the thresholds obtained with the three methods were 10, 18,
      and 26 dB SL at 500 Hz; and 10, 12, and 22 dB SL at 2000 Hz; using 40 Hz ASSR, 90
      Hz ASSR, and tone-burst ABR, respectively. ASSRs with 40 Hz AM stimuli produced
      significantly better results (lowest thresholds with SD=0), whereas the wave-V
      analysis on the tone-burst ABR produced the poorest results. In the averaged
      ABRs, a robust steady-state potential was also visible. Analysis of those steady
      state responses showed estimated thresholds of 13 and 14 dB SL (at 500 and 2000
      Hz, respectively), thus considerably better than the estimated thresholds from
      the wave-V analysis. It is concluded that the 40 Hz ASSR showed superior results,
      especially at 500 Hz.

PMID- 16562564
TI  - Long-term assessment of auditory changes resulting from a single noise exposure
      associated with non-occupational activities.
AB  - We examined the long-term sequelae in both ears of 42 patients who reported the
      occurrence of auditory changes resulting from a single exposure to intense sound
      levels during non-occupational activities. We divided these patients into two
      groups, based upon noise exposures of either continuous duration or single high
      energy impulse. Audiometric data were available for each of these subjects
      shortly after their noise-exposure events and follow-up examinations took place
      more than one year after the noise occurrence (range: 1-16 years). The initial
      median hearing loss for the continuous-type noise exposure group at 3-8 kHz was
      found to be 9 dB, relative to the age-appropriate norms, in the more affected
      ears, and hearing function was found to have returned to normal levels at follow
      up. The same initial hearing loss was measured for the impulse-type noise group,
      but a residual hearing loss of 4 dB was measured at follow-up. Furthermore, the
      majority of the subjects from both groups reported tinnitus and hypersensitivity
      to sound at follow-up, but with minimal impact on their lives.

PMID- 16562565
TI  - Tympanometric norms for Chinese schoolchildren.
AB  - Current tympanometric norms have acknowledged the relevance of age as an
      influencing factor. However, little attention has been afforded to other
      potentialities such as the non-pathological effects of gender, ear asymmetry, and
      racial heritage. This study aimed to examine normative tympanometric findings in
      a large sample of Chinese schoolchildren. Using a Madsen 901 Middle Ear Analyzer,
      data was collected from 269 children (538 ears), ranging in age from 6.2 12.7
      years (mean = 9.4 years, SD = 1.7), in Jiangsu province. Descriptive statistics
      were calculated for the parameters of equivalent ear canal volume (chi = 1.03, SD
      = 0.25, 90% = 0.68 1.46), peak compensated static acoustic admittance (chi =
      0.58, SD = 0.34, 90%=0.26 1.13), tympanometric width (chi = 112, SD = 36, 90% =
      62-156), and peak pressure (chi = -25, SD = 30, 90% = -85 -/+ 10). Statistically
      significant ear asymmetry and grade/age effects were established, although
      differences found were minor. In comparison with past studies in Caucasian
      paediatric populations, the Chinese normative data displayed minimal disparities.

PMID- 16562566
TI  - Insert earphones--a comparison of short-duration signals measured with an
      occluded ear simulator and a 2cc coupler.
AB  - The responses of several insert earphones in the Etymotic 3A series were measured
      with the occluded ear simulator (IEC 60711) and the 2cc coupler (IEC 60126).
      Acoustic clicks following a 100 us rectangular voltage pulse were compared. The
      peak-to-peak equivalent sound pressure levels in the ear simulator were found to
      be 9.2 dB greater than those in the 2cc coupler. The difference was independent
      of type of earphone among those tested. Similar comparisons were made for tone
      pips (brief tones or tone bursts) and continuous tones. For a given drive
      voltage, differences in earphone output were almost the same as the corresponding
      differences in published RETSPLs for the occluded ear simulator and 2cc coupler
      (ISO 389-2).

PMID- 16562567
TI  - MRI of myocardial perfusion.
AB  - An overwhelming number of myocardial perfusion studies are done by nuclear
      isotope imaging. Magnetic resonance imaging during the first pass of an injected,
      contrast bolus has some significant advantages for detection of blood flow
      deficits, namely higher spatial resolution, absence of ionizing radiation, and
      speed of the test. Previous clinical studies have demonstrated that excellent
      sensitivity and specificity can be achieved with MR myocardial perfusion imaging
      for detecting coronary artery disease, and assessment of patients with acute
      chest pain. Furthermore, an absolute quantification of myocardial blood flow is
      feasible, as was demonstrated by comparison of MR perfusion imaging, to
      measurements with isotope labeled microspheres in experimental models. An
      integrated assessment of perfusion, function, and viability, is thus feasible by
      MRI to answer important clinical challenges such as the identification of stunned
      or hibernating, but viable myocardium.

PMID- 16562568
TI  - MRI assessment of myocardial viability.
AB  - In the presence of coronary artery disease, global left ventricular (LV) systolic
      function is a critical prognostic indicator. Because of enhanced therapy for
      myocardial infarction, more patients survive but are left with residual
      myocardial damage that predisposes them to developing CHF in the future. Although
      treatments for CHF are evolving, preventing and minimizing further deteriorations
      in LV function are paramount in this population. Distinguishing severe LV
      dysfunction caused by thinned, infarcted myocardium with fibrosis and scarring
      from that due to viable but dysfunctional myocardium from chronic hypoperfusion
      has significant implications for clinical management. In patients in whom
      noninvasive testing identifies viability, undergoing revascularization improves
      outcomes. Noninvasive imaging techniques used to assess viable myocardium are
      based on demonstrating the presence of one or more of the following features: (1)
      contractile reserve; (2) sufficient perfusion for the delivery of substrates and
      removal of metabolic byproducts; (3) intact myocyte membranes to maintain
      ionic/electrochemical gradients; and (4) preserved metabolism with generation of
      high-energy phosphates. While nuclear and dobutamine echocardiography have been
      widely used for viability assessment, cardiac magnetic resonance imaging (CMR) is
      increasingly becoming an accepted clinical tool, particularly in light of its
      high spatial resolution, intrinsic ability to image 3-dimensionally, and greater
      soft tissue differentiation. Moreover, the versatility of the technique
      potentially allows for the simultaneous assessment of regional wall motion,
      perfusion, and metabolism. An overview of the CMR techniques is presented.

PMID- 16562569
TI  - The evolving role of cardiovascular magnetic resonance imaging in nonischemic
      cardiomyopathy.
AB  - Over the last several years, the role of cardiac magnetic resonance imaging in
      the diagnosis and management of heart failure has been rapidly expanding. The
      techniques unrivaled flexibility, accuracy in defining ventricular structure and
      function, and capacity to characterize tissue makes it particularly well suited
      for the study of the nonischemic cardiomyopathies. In this article, we provide an
      overview of the existing literature highlighting the diagnostic utility and
      prognostic power of cardiac magnetic resonance imaging in the nonischemic
      cardiomyopathies.

PMID- 16562570
TI  - Computed tomographic cardiovascular imaging.
AB  - Over the last decade, there has been increased recognition that atherosclerosis
      imaging adds greatly to the ability to identify patients at high risk for cardiac
      events. Technologies such as electron beam computed tomography and carotid
      intimal media thickness have contributed significantly to our understanding of
      the prevalence of preclinical atherosclerosis and its consequences. Current data
      suggest that elevated calcium scores are predictive of future cardiac events,
      independently and incrementally to traditional cardiac risk factors. The
      approximate predictive power is 10-fold for scores > 100, based upon current
      studies now reported. Guidelines and policy toward these modalities have shifted,
      with increased recognition of the importance among experts in cardiology,
      lipidology, and preventive medicine. Because most adverse events related to
      atherosclerosis occur in individuals at an intermediate risk, data suggest that
      it will be most cost-effective to concentrate screening efforts on this group of
      patients. This article reviews the current understanding of the value of coronary
      artery calcium screening in asymptomatic and symptomatic patients. Accurate
      measurement of subclinical coronary atherosclerosis should significantly improve
      the accuracy of global cardiovascular risk prediction, and allow for tracking of
      atherosclerosis burden, as well as better prediction of future cardiovascular
      events. Finally, by identifying high-risk patients, CAC may help select those
      patients who would benefit most from additional testing (e.g., non-invasive
      stress imaging) and intensification of medical therapy; CAC should have a
      significant impact on early detection and management of CAD.

PMID- 16562571
TI  - Computed tomographic angiography of the coronary arteries: techniques and
      applications.
AB  - Computed tomographic coronary angiography (CT-CA) is a direct but minimally
      invasive method of visualizing coronary arteries. Multidetector-row computed
      tomography (MDCT) is currently the CT modality most commonly used for coronary
      artery imaging. MDCT has been successfully used to detect stenoses in coronary
      arteries and coronary artery bypass grafts and to assess congenital coronary
      anomalies. Patients should not undergo CT-CA with MDCT if they have an irregular
      heart rhythm, a heart rate greater than 70 beats/min, and contraindications to
      pharmacologic agents for heart rate control, or if they have severe coronary
      artery disease or are likely to require revascularization.

PMID- 16562572
TI  - Non-coronary cardiac CT imaging.
AB  - Cardiac multidetector CT (MDCT) has moved from purely anatomic imaging, to
      assessment of cardiac function. Significant advances since the advent of
      multidetector CT now make it feasible to assess not only the coronary arteries,
      but also ejection fraction, ventricular volumes, myocardial mass and the presence
      of wall-motion abnormalities. Advances include improvements in EKG-gating,
      including improvements in temporal resolution, as well as the addition of delayed
      contrast-enhanced methods. Anatomic imaging has improved as well, with thinner
      collimation and better reconstruction methods. Three-dimensional software
      programs now permit excellent surface rendered displays and multiplanar
      reconstructions suitable as surgical and procedural "road maps."

PMID- 16562573
TI  - Monitor observation status to make sure new codes are being used.

PMID- 16562574
TI  - New DRGs may affect your hospital's reimbursement.

PMID- 16562575
TI  - Unit improves care for short-stay cardiac patients.

PMID- 16562576
TI  - Navigators guide patients through the continuum.

PMID- 16562577
TI  - Case managers take the lead on quality initiatives.

PMID- 16562578
TI  - Program helps to boost copay collections.

PMID- 16562579
TI  - Letting go of the 'that's not how we do it here' mindset.

PMID- 16562580
TI  - Patient safety alert. Study: quality, patient safety improving at a modest pace.

PMID- 16562581
TI  - The diagnosis and care of transsexual children and adolescents: a pediatric
      endocrinologists' perspective.
AB  - The normally developed child whose gender identity and anatomic sex disagree is
      referred to as a transgendered child, or as used subsequently in this text, a
      transsexual. The ramifications of this disagreement include a high risk of
      psychiatric conflict and maladjustment, for both the individuals themselves and
      their families. Despite the efforts of researchers to systematically study this
      group of children, many fundamental questions remain. In many respects, those
      lingering questions are shared by patients with physical intersex who have been
      cared for by pediatric endocrinologists. In intersex and transsexual patients,
      the medical community, although sincerely interested, remains wary to intervene
      in ways that may lead to further inconsistency between anatomic sex and adult
      gender identity. A perspective on the problems of differentiating permanent from
      transient gender identity, some thoughts on the most appropriate management of
      the transsexual child/adolescent as well as remaining questions are discussed.
      Both the flexible and therefore potentially misleading gender identity in
      children and the medical communities' pledge to first do no harm (primum non
      nocere) have regrettably fostered disharmony between gender disordered patients,
      their families, and the practitioners who want to help them.

PMID- 16562582
TI  - Surgical, medical and psychological dilemmas of sex reassignment: report of a
      46,XY patient assigned female at birth.
AB  - This is a report of a 16 year-old 46,XY male who was reassigned female and had
      feminizing surgery during infancy because of what was judged to be inadequate
      genital masculinization. This patient had a dysgenetic testis that was shown to
      be producing testosterone during infancy. Although initially the reassignment
      appeared to be successful, psychological problems became progressively more
      severe during childhood to incapacitation by age 10 years. After it was verified
      that he had a male sexual identity, reassignment as male began, initially by
      living as a boy, then with testosterone therapy. Staged phalloplasty surgery was
      begun at age 16 years. Currently he has an adult-sized penis, although its
      function is not yet clear. Sadly, none of the steps to align his sex assignment
      to his perception as male has significantly alleviated his psychological issues
      and he continues to be severely impaired and socially compromised. Major issues
      include the crippling psychiatric disease that is resistant to psychotherapy and
      surgical problems with phalloplasty after surgery at infancy that involved
      reduction of the phallus with recession of the glans to the typical clitoral
      location. The glans was left intact at the anterior base of the phallus. Genital
      responsiveness during sexual activity and satisfaction are as yet unknown.

PMID- 16562583
TI  - Lack of differences between males with or without perceived same sex attraction.
AB  - Adolescent males are often concerned that they may be homosexual because of a
      sense of sexual attraction to other males. This not uncommon concern is often
      expressed to pediatric endocrinologists who come into contact with these boys
      because of concerns with abnormal pubertal development. To explore the character
      and prevalence of these types of homosexual concerns we assessed the perceptions
      of a group of healthy adolescent males using a structured questionnaire. The aim
      of this study was to determine whether males concerned about homosexual
      tendencies manifest a unique self-perception profile or interact differently with
      others. A multi-item questionnaire regarding demographic, behavioral,
      psychological and sexual characteristics was administered to 52 18-24 year-old
      males. Overall, there were few differences between males admitting to an
      adolescent homosexual attraction to males and males without this attraction.
      Differences between these two groups included more exposure to some kinds of
      pornography (including male to male imagery), noticeable psychosexual responses
      to male pornography, internal questioning over homosexual tendencies, comparisons
      of genitalia and perceptions of body build. There were no differences in
      demographics, family structure, religious beliefs, socio-economic status,
      knowledge of puberty, inter-personal relationships or sources of information
      about sexuality.

PMID- 16562584
TI  - Weight gain in craniopharyngioma--a model for hypothalamic obesity.
AB  - OBJECTIVES: To evaluate (1) the pattern of post-operative weight gain and (2) the
      risk factors associated with the development of post-operative weight gain and
      obesity in children treated for craniopharyngioma. STUDY DESIGN: The records of
      43 children who had primary craniopharyngioma resection were reviewed.
      Neurological, endocrine, anthropometric and radiological risk factors for the
      development of obesity and for post-operative increase in BMI SDS were analyzed.
      RESULTS: Twenty-five patients (58%) became obese post-operatively. Obesity was
      significantly associated with higher BMI SDS at presentation and pre-operative
      hydrocephalus (p < 0.05). Increased BMI SDS from 0-12 months was significantly
      associated with post-operative MRI evidenced hypothalamic damage and higher BMI
      at presentation (p < 0.05). CONCLUSIONS: Children who developed hypothalamic
      obesity had a significant, rapid BMI increase over the first 6 months, followed
      by stabilization, with no regression of BMI SDS.

PMID- 16562585
TI  - Dexamphetamine use for management of obesity and hypersomnolence following
      hypothalamic injury.
AB  - Unrelenting weight gain, morbid obesity and disturbance of the sleep-wake cycle
      are well-recognized sequelae of hypothalamic injury. These health problems and
      their risk of significant associated co-morbidity drive the search for potential
      treatment modalities. OBJECTIVE: To report effects on weight change and
      wakefulness in a cohort of 12 patients with structural hypothalamic lesions
      treated with low-dose dexamphetamine. METHOD: Retrospective review of case notes.
      RESULTS: Twelve patients received dexamphetamine 5 mg twice daily (median
      duration 13 months in males, 15 months in females). Ten of 12 patients
      experienced either stabilisation of weight or weight loss on treatment (median
      loss -0.7 SDS in males, -0.44 SDS in females). Eleven patients reported
      improvement in daytime wakefulness and/or concentration and exercise tolerance.
      CONCLUSION: Low-dose dexamphetamine therapy has a positive impact on inexorable
      weight gain and daytime somnolence following hypothalamic injury.

PMID- 16562586
TI  - Type 2 diabetes mellitus in African-American adolescents: impaired beta-cell
      function in the face of severe insulin resistance.
AB  - We have previously demonstrated abnormalities in insulin secretion in adolescents
      with type 2 diabetes mellitus (DM2) in response to the mixed meal test and to
      glucagon. In order to further assess beta-cell function in DM2, we measured
      insulin and C-peptide responses to oral glucose in adolescents with DM2 in
      comparison to non-diabetic obese and lean adolescents. We studied 20 patients
      with DM2, 25 obese adolescents with matching body mass index (BMI) (33.8 +/- 1.4
      vs 34.3 +/- 1.0 kg/m2), and 12 non-obese control adolescents (BMI 22.6 +/- 0.6
      kg/m2). Mean age, sex and sexual maturation did not differ between the three
      groups. All adolescents with DM2 had negative islet cell antibodies (ICA); five
      patients were on diet and 15 on insulin treatment. Fasting lipid profiles were
      determined in all participants. Plasma glucose and serum C-peptide and insulin
      levels were measured at 0, 30, 60, 90, and 120 min after an oral glucose load.
      The C-peptide increment (deltaCP) was calculated as peak minus fasting C-peptide.
      Area under the curve (AUC) was estimated using the trapezoid method. Insulin
      resistance was estimated using the HOMA model (HOMA-IR). The first phase of
      insulin secretion (PH1) was computed using a previously published formula. Serum
      triglyceride levels were significantly higher in the patients with DM2 compared
      to the non-obese controls (1.4 +/- 0.1 vs 0.9 +/- 0.1 mmol/l; p = 0.02). Plasma
      glucose AUC was greater in the patients with DM2 compared to the obese and non
      obese control groups (1,660 +/- 130 vs 717 +/- 17 vs 647 +/- 14 mmol/l x min; p <
      0.0001). ACP was lower in adolescents with DM2 than in obese and non-obese
      adolescents (761 +/- 132 vs 1,721 +/- 165 vs 1,225 +/- 165 pmol/l; p < 0.001).
      Insulin AUC was lower in the patients with DM2 compared to obese controls (888 +/
      206 vs 1,606 +/- 166 pmol/l x h; p = 0.009), but comparable to that of the non
      obese controls (888 +/- 206 vs 852 +/- 222 pmol/l x h; p = 0.9). Insulin AUC was
      also higher in the obese than in the non-obese group (p = 0.05). PH1 was
      significantly higher in the obese group compared to the patients with DM2 as well
      as to the non-obese controls (2,614 +/- 2,47.9 vs 929.6 +/- 403.5 vs 1,946 +/-
      300.6 pmol/l, respectively; p = 0.001). PH1 was also higher in the non-obese
      controls than in the patients with DM2 (p = 0.05). HOMA-IR was three-fold higher
      in the patients with DM2 than in the BMI-matched obese group, and five-fold
      higher than in the lean controls (14.3 +/- 1.2 vs 5.4 +/- 0.8 vs 2.9 +/- 0.4; p =
      0.0002). Adolescents with DM2 have dyslipidemia, a significant cardiovascular
      risk factor. Decreased beta-cell function is characteristic of adolescents with
      DM2 in the presence of severe insulin resistance.

PMID- 16562587
TI  - Molecular genetic analysis of MODY candidate genes in Japanese patients with non
      obese juvenile onset diabetes mellitus.
AB  - We analyzed 84 Japanese patients with juvenile-onset (before 18 years of age) non
      obese diabetes mellitus (DM) for mutations in the genes for HNF-1alpha, HNF
      4alpha and HNF-1beta. In HNF-1alpha, previously reported mutations (R271W and
      R272C) and one novel sequence variant (at nucleotide -129/-130 insTTGGGG of the
      promoter region) were identified in three different patients. In vitro functional
      study of the new promoter variant demonstrated that the transcriptional activity
      was 1.6-2.0 times higher than that of the wild-type. This may lead to
      overexpression of HNF-1alpha and subsequent negative regulation of the target
      genes of HNF-1alpha. No mutation was identified in the HNF-4alpha and HNF-1beta
      genes. In this study on a small series of non-obese Japanese patients with
      juvenile-onset DM, the prevalence of MODY3 was 3.5%. The significance of the new
      promoter variant in the development of DM is unclear; however, a promoter
      mutation in the HNF-1alpha gene could be diabetogenic.

PMID- 16562588
TI  - Prevalence of autoantibodies associated with thyroid and celiac disease in
      Ullrich-Turner syndrome in relation to adult height after growth hormone
      treatment.
AB  - A prospective, multicenter study of patients with Ullrich-Turner syndrome (UTS)
      was conducted to estimate the prevalence of autoantibodies to tissue
      transglutaminase (tTg), thyroid stimulating hormone receptor (TSH-R),
      thyroglobulin (TG) and thyroid peroxidase (TPO) in relation to adult height after
      long-term growth hormone (GH) treatment. Out of 347 near-adult (> 16 years)
      patients with UTS from 96 German centers, whose longitudinal growth was
      documented within the Pharmacia International Growth Study (KIGS), 188 returned
      for a standardized follow-up visit at a median chronological age of 18.7 (16.0
      23.6) years (bone age > 15 years). Serum samples of 120 patients were obtained
      for central measurements of TSH, thyroxine (T4) and free T4 and autoantibodies by
      standard immunoassays. Information regarding thyroid disease, karyotype and
      anthropometric data was extracted from the KIGS database. Thirty-six percent of
      the patients with UTS had positive TG and/or TPO autoantibodies and 4% had
      positive tTg autoantibodies, whereas 2% had positive TG and/or TPO autoantibodies
      as well as positive tTg autoantibodies. TSH-R autoantibodies were undetectable in
      all patients. The detection of autoantibodies was unrelated to a specific
      karyotype. Median height standard deviation scores (SDS, UTS) at start of GH
      treatment (0.43; -1.07, 1.85) and at follow-up (1.36; -0.11, 2.57) were
      comparable in all patients independent of their antibody status. The total
      deltaheight SDS, however, was higher in patients with negative autoantibody
      titers (1.08; -0.03, 2.25) compared to those with positive antibody titers (0.68;
      -0.44, 1.82; p < 0.01). Our study confirms the high prevalence of autoantibodies
      in patients with UTS predisposing them to autoimmune thyroid disease and celiac
      disease, and indicates for the first time that autoimmune pathologies may
      interfere with GH therapy and thus compromise final height. Therefore, medical
      care for patients with UTS should routinely include screening for these
      autoimmune disorders in order to assure early detection and appropriate
      treatment.

PMID- 16562589
TI  - Familial Mediterranean fever and growth: effect of disease severity and
      colchicine treatment.
AB  - OBJECTIVE: To evaluate the effect of disease severity and colchicine treatment on
      height and weight parameters in children with familial Mediterranean fever (FMF).
      METHODS: Thirty prepubertal children (19 M, 11 F) were studied retrospectively. Z
      score values of height, growth velocity, weight and body mass index were obtained
      over 1.84 +/- 1.14 years before and 2.58 +/- 1.55 years during colchicine
      therapy. Disease severity was evaluated by a specific score for FMF. RESULTS: By
      comparison to growth before treatment, during colchicine therapy height SDS
      increased from -1.00 +/- 1.17 to -0.54 +/- 0.96 (p < 0.001) and weight SDS
      increased from -0.74 +/- 1.09 to -0.47 +/- 1.06 (p = 0.008). An effect of disease
      severity on growth pattern could not be detected. Height SDS during therapy was
      negatively correlated with age at colchicine initiation. CONCLUSIONS: Colchicine
      therapy has a positive effect on both height and weight parameters in children
      with FMF. Early initiation of treatment is beneficial for height gain.

PMID- 16562590
TI  - Pamidronate treatment of steroid associated osteonecrosis in young patients
      treated for acute lymphoblastic leukaemia--two-year outcomes.
AB  - AIMS: To assess outcomes of young patients with osteonecrosis (ON) treated with
      pamidronate in terms of relief of pain, prevention of progress and bony collapse
      of involved area. PATIENTS AND METHODS: A non-randomised interventional study in
      six patients with a history of acute lymphoblastic leukaemia (ALL) for which
      treatment protocols included long-term, high dose use of glucocorticoids.
      Subsequent development of ON was treated with a bisphosphonate (pamidronate) for
      2 years. Mobility and pain control were assessed regularly with MRI and X-ray of
      affected areas at 0, 12 and 24 months. RESULTS: Reduction in pain was reported in
      four of six patients in the first year with increased mobility. Two patients who
      had radiological evidence of joint destruction prior to treatment and when
      continued on corticosteroids reported no improvement in pain or mobility. In the
      second year, patients who started treatment in the first few months after
      diagnosis were stable while patients who had treatment initiated later
      deteriorated but had less pain than prior to treatment with pamidronate. MRIs of
      affected areas were completely unchanged over 2 years. X-rays revealed no new
      bony collapse in four of six patients after 12 months of treatment. However,
      three of six patients continued to undergo extensive collapse of femoral heads
      (one at 12 months, two at 24 months) and all these required urgent hip
      replacement. CONCLUSION: Pamidronate treatment has a palliative effect in control
      of pain and may delay the natural history of bony collapse in the acute phase of
      ON, especially in early treated patients, but does not prevent late bone collapse
      and joint destruction in corticosteroid treated patients with ALL. Larger studies
      are needed to provide evidence as to whether bisphosphonate is indicated for
      treatment of ON for patients using corticosteroids.

PMID- 16562591
TI  - Oral alendronate therapy for severe vitamin D intoxication of the infant with
      nephrocalcinosis.
AB  - Vitamin D intoxication is a well-known cause of hypercalcemia in children. We
      report here the use of oral alendronate for the treatment of hypercalcemia due to
      vitamin D intoxication in a 7 month-old infant with nephrocalcinosis. The serum
      calcium levels were normalized without complications. Oral alendronate therapy
      may be safely used in hypercalcemia due to vitamin. D intoxication in pediatric
      patients with nephrocalcinosis resistant to hydration, diuretics or
      corticosteroids.

PMID- 16562592
TI  - Isolated central diabetes insipidus in a newborn with congenital toxoplasmosis.
AB  - We present a 5 day-old male newborn with isolated central diabetes insipidus due
      to congenital toxoplasmosis. This patient was referred to us for hydrocephalus.
      As we investigated the aetiology of the hydrocephalus, the patient's serum and
      cerebrospinal fluid tested positive for toxoplasmosis via ELISA and polymerase
      chain reaction. Computed tomography showed obstructive hydrocephalus and
      disseminated cranial calcifications. Central diabetes insipidus developed on the
      10th day, apparently as a result of the toxoplasmosis infection, and was treated
      successfully with oral desmopressin.

PMID- 16562593
TI  - Ovarian adrenal rest tissue in congenital adrenal hyperplasia--a patient report.
AB  - We report a young girl who died in an Addisonian crisis due to previously
      undiagnosed congenital adrenal hyperplasia (CAH), in whom ovarian adrenal rest
      tissue was detected at postmortem histopathological examination. This is a very
      rare complication in female patients with CAH with only two previously reported
      cases.

PMID- 16562594
TI  - The Fifth European Growth Plate Working Group Symposium. 21st September 2005,
      Lyon, France.
AB  - The regulation of longitudinal bone growth at the growth plate occurs through the
      tightly controlled interaction of circulating systemic hormones and locally
      produced peptide growth factors, the net result of which is to trigger changes in
      gene expression by growth plate chondrocytes. These molecular events lead to
      carefully orchestrated alterations in chondrocyte size, extracellular matrix
      components, secreted enzymes and growth factors, and receptor expression. The
      result of these events is calcification of the matrix, chondrocyte apoptosis, and
      the completion of endochondral bone formation. Although over the past decade
      advances in molecular and cellular biology have increased our understanding of
      skeletal biology and the process of endochondral ossification, many of the
      signaling pathways and their interactions remain poorly understood in the growth
      plate. The European Growth Plate Working Group (EUROGROP) was established in 2000
      with the aim to bring together groups of basic and clinical researchers from
      Europe with an interest in the normal biology and pathophysiology of the growth
      plate. The 5th EUROGROP Symposium, held in Lyon, France, as a satellite symposium
      to the 7th Joint Meeting of ESPE/ LWPES 2005, enabled researchers, coming from
      all parts of the world, including South America, Australia, Asia and Japan, to
      discuss their ongoing studies and exchange technical information. Topics ranged
      from the search for the molecular mechanisms of growth plate senescence to IGF-I
      and sugar metabolism in skeletal growth centers, while techniques discussed
      included microarray analysis of rat growth plates and the use of human
      mesenchymal stem cells as a model of chondrocyte differentiation.

PMID- 16562595
TI  - Initial management of infants with intersex conditions in a tertiary care center:
      a cautionary tale.

PMID- 16562596
TI  - Re: Houk CP, et al. Intersex classification scheme: a response to the call for a
      change. J Pediatr Endocrinol Metab 2005; 18: 735-738.

PMID- 16562597
TI  - [Nutrition and chronic renal failure: a puzzle!].

PMID- 16562598
TI  - [Chronic renal failure: what diet?].
AB  - A low protein diet has been traditionally advocated in patients with chronic
      renal failure (CRF), in order to slow its progression. However, CRF is often
      associated with malnutrition, aggravating its prognosis, especially in elderly
      patients. In severe CRF, the spontaneous reduction of appetite coupled with
      additional restrictions regarding sodium, potassium and phophates may further
      impact on nutrition status. The potential benefit of a low protein diet is
      therefore questionable. We only recommend a moderately restricted protein diet
      (0,8 g/kg/day) in selected patients with no sign of malnutrition. This strategy,
      if applied, must be supported by a multidisciplinary approach involving a
      nephrologist and a specialised dietician. Additional dietary restrictions are not
      justified, except in particular situations.

PMID- 16562599
TI  - [Malnutrition on dialysis: the end of a fatality].
AB  - Protein-energy malnutrition in patients treated with haemodialysis (HD) is a
      complex, multifactorial and prevalent problem, starting well ahead of the
      dialysis program. It is associated with an increased morbidity and mortality.
      Uraemic patients are relatively resistant to nutrients because of metabolism
      abnormalities. Prevention of malnutrition is therefore more efficient than
      treatment per se. Classical supplementation including oral nutritional
      supplements, intradialytic parenteral nutrition and enteral nutrition remain
      efficient, if applied for a sufficient time. A global approach coupling
      supplementation and strategies designed to optimise metabolism abnormalities
      should increase treatment efficacy and improve the outcome and quality of life of
      these patients.

PMID- 16562600
TI  - [Obesity: what impact on renal function?].
AB  - The increasing prevalence of obesity is a major public health concern, affecting
      more than one third of the Swiss population. The renal effects of obesity per se,
      independent of hypertenison or diabetes, though, are less known. Obesity is
      positively correlated with proteinuria and the development of glomerulomegaly and
      focal segmental glomerulosclerosis. The pathophysiology of the obesity-associated
      kidney disease is complex, including hemodynamic and physical factors and
      increased synthesis of vasoactive and fibrogenic substances by adipose tissue.
      The most important therapeutic approach is weight reduction. Angiotension
      converting enzyme (ACE) inhibition is effective in reducing proteinuria, but
      longer follow-up is required to determine the long term benfits of ACE
      inhibition.

PMID- 16562601
TI  - [Could cystatine C replace creatinine as a market of glomerular filtration
      rate?].
AB  - Measurement of glomerular filtartion rate (GFR) is crucial for the detection and
      follow-up of an early renal impairment. Inulin clearance or radio-isotopes are
      the gold standard but they cannot be used routinely. Serum creatinine and
      creatinine clearance are the most widely used, but they lack sensibility to
      detect an early renal impairment and in cases of obesity, malnutrition or
      advanced age. Looking for a more reliable marker is necessary and cystatin C
      seems to be interesting. This molecule is constantly produced by nucleated cells,
      then freely filtrated and catabolized in the proximal tube. Clinical studies
      showed that cystatin C might be a more reliable marker of GFR in determined
      groups of patients. Moreover this molecule may have an other interest as a
      predictive risk factor or mortality, especially for cardiovascular events.

PMID- 16562602
TI  - [Anticoagulation in patients with chronic renal failure].
AB  - Anticoagulation may be difficult to implement in patients suffering from chronic
      renal failure on account of platelet disorders and impaired clearance of some
      anticoagulant drugs. Although no adjustment of heparin and coumarin dosage is
      necessary, more frequent testing of coagulation pathways may be required when
      these drugs are used in patients with renal failure. Long-term use of LMWH should
      be implemented cautiously with regular testing of anti-factor Xa activity and a
      half-dose may be advocated in patients with a creatinine clearance < 30 ml/mn.
      Danaparoid and thrombin inhibitors should be used mainly in patients suffering
      from renal failure and heparin-induced thrombocytopenia with regular monitoring
      of coagulation tests.

PMID- 16562603
TI  - [Clinical and genetics aspects of Alport syndrome].
AB  - Microscopic haematuria of glomerular origin, without known aetiology, should
      raise the suspicion of Alport Syndrome IASI in children as well as in adults. The
      genetic mutations causing AS lie in the genes encoding for the alpha3, alpha4 and
      alpha5 chains of the collagen type IV, the main constituent of glomerular
      basement membranes (GBM). The various mutations and modes of transmission of the
      disease account for the heterogeneous clinical presentations. No specific
      treatment of AS is currently available. However, a better understanding of the
      GBM's ultrastructure, in particular of type IV collagen, will hopefully enable
      the identification of novel therapeutic targets.

PMID- 16562604
TI  - [Kidney cancer: from biology to clinical medicine].

PMID- 16562605
TI  - [Quinolones to treat pneumonia: what should one really think about that?].

PMID- 16562606
TI  - [Accidental arterial catheterization during insertion of a central line for
      internal jugular access].

PMID- 16562607
TI  - [Quality assurance].

PMID- 16562608
TI  - [Poultry from the Union, time for confinement].

PMID- 16562609
TI  - [Chikungunya, when politicians are interested in arbovirus infections (I)].

PMID- 16562610
TI  - [Epidemics and role of the scapegoat].

PMID- 16562611
TI  - [Is wellbeing a goal?].

PMID- 16562612
TI  - Cysts and pseudocysts of the maxillary antrum revisited.
AB  - There is considerable confusion in the literature regarding the terminology and
      distribution of cysts and pseudocysts of the maxillary antrum, which are
      therefore often lumped together as dome-shaped shadows on the floor of the
      maxillary sinus. We report a case of a mucocoele of the maxillary antrum that
      occurred in a 25-year-old male and review the clinical, radiographic and
      histological features of cysts and pseudocysts of the maxillary sinus including
      antral mucocoeles, postoperative maxillary cysts, pseudocysts and retention
      cysts; and highlight some of the pertinent distinguishing features. Awareness of
      the appropriate nomenclature and correlation of clinical, radiographic and
      histological features will generally result in the correct diagnosis and proper
      treatment.

PMID- 16562613
TI  - Self-etching bonding systems: in-vitro shear bond strength evaluation.
AB  - The purpose of this in vitro study was to compare the dentine shear bond strength
      of five self-etching bonding agents with that of a total-etch dentine bonding
      agent (used as control). Sixty recently extracted third molar teeth were mounted
      in acrylic resin and the occlusal surfaces ground to expose superficial dentine.
      A standardised smear layer was created by polishing with wet 600-grit SiC paper.
      Products evaluated were Xeno III (XIII), Clearfil SE Bond (SE), ABF (ABF),
      Optibond Solo Self-etch (OS), Adper Prompt-L-Pop (PLP) and the control,
      Scotchbond Multipurpose Plus (SBMP). Resin stubs were bonded to the dentine using
      the bonding agents according to manufacturer's instructions. Composite stubs were
      manufactured using an Ultradent jig and two increments of Z100, A1 shade
      composite. The bonds were subsequently stressed to failure with an Instron
      testing machine, operating at a crosshead speed of 0.5 mm/min. The data was
      statistically analysed using ANOVA (alpha < or = 0.05). The mean SBS (MPa) were:
      SBMP (Control) = 24.1 +/- 7.6; XIII = 17.3 +/- 4.1; SE = 26.2 +/- 7.8; ABF = 25.9
      +/- 4.3; OS = 21.9 +/- 3.9 and PLP = 15.4 +/- 3.1. The shear bond strengths of
      both XIII and PLP to dentine were significantly lower than the control SBMP (p <
      0.05). The remaining three products (SE, ABF and OS) displayed bond strengths
      comparable to the control (p > 0.05). Further research into cut (ground) and un
      cut (un-ground) enamel shear bond strength and micro-leakage using these bonding
      agents are needed.

PMID- 16562614
TI  - Handling protocol of posterior composites--part 3: matrix systems.
AB  - Two of the major clinical problems related to direct posterior composite
      restorations are the clinician's inability to establish an ideal proximal contour
      and interproximal contact, which, in turn, can lead to continual food impaction
      and periodontal disease. The reason for this is that composites provide little
      internal force to counteract the force from the matrix. Therefore, unlike
      amalgams, which possess a very high resistance to deformation, composites are
      easily forced back into their original position by a tight circumferential matrix
      band. Thus, although tight contacts in small-moderate sized cavities may be
      possible for posterior composites using circumferential matrices, special matrix
      systems and wedging techniques are being required to establish a proper contact,
      especially when cavities with a wide buccolingual width are being restored.

PMID- 16562615
TI  - Dental implant guide--Radiological.

PMID- 16562616
TI  - Sedation corner. What are the possible problems facing the sedationist when he
      plans introvenous sedation in the obese patient?

PMID- 16562617
TI  - General practitioner's pathology case 1. Gingival cyst.

PMID- 16562618
TI  - General practitioner's radiology case 38. Tuberculosis osteomyelitis of the jaws.

PMID- 16562619
TI  - Richard Carmona, MD, MPH, FACS--Surgeon General. Interview by Eileen Lukes.

PMID- 16562620
TI  - Under what circumstances should a case manager seek an independent medical
      evaluation, and is there a good method of selecting an examiner for this purpose?

PMID- 16562621
TI  - Rural community leaders' perceptions of environmental health risks: improving
      community health.
AB  - Qualitative description was used to explore how rural community leaders frame,
      interpret, and give meaning to environmental health issues affecting their
      constituents and communities. Six rural community leaders discussed growth,
      vulnerable families, and the action avoidance strategies they use or see used in
      lieu of adopting health-promoting behaviors. Findings suggest intervention
      strategies should be economical, use common sense, be sensitive to regional
      identity, and use local case studies and "inside leadership." Occupational health
      nurses addressing the disparate environmental health risks in rural communities
      are encouraged to use agenda-neutral, scientifically based risk communication
      efforts and foster collaborative relationships among nurses, planners, industry,
      and other community leaders.

PMID- 16562622
TI  - Friction-reducing devices for lateral patient transfers: a biomechanical
      evaluation.
AB  - The purpose of this study was to evaluate the efficacy of friction-reducing
      devices used for lateral patient transfers. A mannequin used to represent a
      dependent patient was transferred laterally from bed to stretcher. One male
      investigator repeated this task using 11 comparable lateral transfer aids or
      techniques. Applied force was measured using a dynamometer; postural analysis was
      prepared from still photography. Mean applied force, spinal forces, and
      population strength capabilities were calculated. The most efficacious mechanism
      for lateral patient transfers had extendable pull straps, low-friction material,
      and optimally located handles. Findings of this study will aid occupational
      health and safety clinicians and hospital-based caregivers in the selection of
      appropriate technologies to be used during lateral patient transfers. These
      devices improve patient safety and reduce the risk of back injury to caregivers.

PMID- 16562623
TI  - Cardiovascular risk among older Hispanic women: a pilot study.
AB  - This study used a descriptive correlational design to describe the relationship
      between cardiovascular risk and anxiety, spirituality, acculturation, and the
      objective indices of cardiac risk among a sample of 21 adult Hispanic women.
      Objective indices of risk included weight, blood pressure, blood lipids, and
      glucose. Four survey instruments were used to assess anxiety, spirituality,
      acculturation, and perceived risk. Findings revealed that all study participants
      had 3 or more risk factors, placing them in the moderate risk category for
      developing heart disease or having a heart attack within 10 years. State and
      trait anxiety scores were lower than the normative samples for adult women.
      Spirituality scores were higher than average; individuals with higher anxiety
      scores had lower spirituality scores. More research is needed to determine the
      health needs of unskilled workers with limited education in employment settings.

PMID- 16562624
TI  - Changing the disability climate: promoting tolerance in the workplace.
AB  - Disability climate is a key determinant of the successful integration of
      individuals with disabilities into the work force and a major influence on the
      level of occupational stress experienced by this population. Industry-specific
      attitudes regarding disabilities have an effect on disability climate as
      perceived by workers, as do formal and informal policies, procedures, and
      practices. Occupational health nurses can impact organizational disability
      climates through implementation of disability climate programs, thus improving
      workplace conditions for workers with disabilities and reducing occupational
      stress.

PMID- 16562625
TI  - Eating breakfast helps sustain weight loss.

PMID- 16562626
TI  - Sites of neuronal excitation by epiretinal electrical stimulation.
AB  - Action potentials arising from retinal ganglion cells ultimately create visual
      percepts. In persons blind from retinitis pigmentosa and age-related macular
      degeneration, viable retinal ganglion cells remain, and the retina can be
      stimulated electrically to restore partial sight. However, it is unclear what
      neuronal elements in the retina are activated by epiretinal electrical
      stimulation. This study investigated the effects of cellular geometry, electrode
      to neuron distance, stimulus duration, and stimulus polarity on excitation of a
      retinal ganglion cell with an epiretinal electrode. Computer-based compartmental
      models representing simplified retinal ganglion cell morphology provided evidence
      that the threshold for excitation was lower when an electrode was located in
      proximity to the characteristic 90 degrees bend in the axon of the retinal
      ganglion cell than when it was located over a passing axon of the nerve fiber
      layer. This electrode-position-dependent difference in threshold occurred with
      both cathodic and anodic monophasic stimuli, with point source and disk
      electrodes, at multiple electrode-to-neuron distances, and was robust to changes
      in the electrical properties of the model. This finding reveals that the physical
      geometry of the retinal ganglion cells produces stimulation thresholds that
      depend strongly on electrode position. The low excitation thresholds near the
      bend in the axon will result in activation of cells local to the electrode at
      lower currents than required to excite passing axons. This pattern of activation
      provides a potential explanation of how epiretinal electrical stimulation results
      in the production of punctuate, rather than diffuse or streaky phosphenes.

PMID- 16562627
TI  - Modulation effects of epidural spinal cord stimulation on muscle activities
      during walking.
AB  - Epidural spinal cord stimulation (ESCS) combined with partial weight bearing
      therapy (PWBT) has been reported to facilitate recovery of functional walking for
      individuals after chronic incomplete spinal cord injury (ISCI). Muscle activities
      were analyzed in this report to examine the modulation effect of ESCS on muscle
      recruitment during gait training. Two ISCI individuals participated in the study
      and both are classified as ASIA C with low motor scores in the lower limbs.
      Stimulating electrodes were placed at the epidural space over T10-L2 spinal
      segments, along the midline in participant 1 (S1), and off-midline in participant
      2 (S2). Surface electromyograms (EMGs) from leg muscles under both ESCS ON and
      OFF conditions recorded during treadmill gait were analyzed in time-frequency
      domains. ESCS application produced acute modulations in muscle activities in both
      participants, but the observed pattern, magnitude, and spectral content of the
      EMGs differed. In S1, ESCS induced a significant shift in the temporal pattern of
      muscle activity toward normal comparing with that when ESCS was OFF, though
      without eliciting noticeable change in frequency distribution between ESCS ON and
      OFF conditions. When ESCS was applied in S2, a modulation of EMG magnitude was
      observed and, consequently, improved joint kinematics during walking. In this
      case, a stimulation entrainment appeared in time-frequency analysis. The results
      suggest that ESCS activates neural structures in the dorsal aspect of the spinal
      cord and facilitates gait-related muscle recruitment. The exact effects of ESCS
      depend on the electrode placement and possibly injury history and residual
      functions, but in general ESCS produces a positive effect on improved walking
      speed, endurance, and reduced sense of effort in both ISCI subjects.

PMID- 16562628
TI  - Robust classification of EEG signal for brain-computer interface.
AB  - We report the implementation of a text input application (speller) based on the
      P300 event related potential. We obtain high accuracies by using an SVM
      classifier and a novel feature. These techniques enable us to maintain fast
      performance without sacrificing the accuracy, thus making the speller usable in
      an online mode. In order to further improve the usability, we perform various
      studies on the data with a view to minimizing the training time required. We
      present data collected from nine healthy subjects, along with the high accuracies
      (of the order of 95% or more) measured online. We show that the training time can
      be further reduced by a factor of two from its current value of about 20 min.
      High accuracy, fast learning, and online performance make this P300 speller a
      potential communication tool for severely disabled individuals, who have lost all
      other means of communication and are otherwise cut off from the world, provided
      their disability does not interfere with the performance of the speller.

PMID- 16562629
TI  - Steady-state somatosensory evoked potentials: suitable brain signals for brain
      computer interfaces?
AB  - One of the main issues in designing a brain-computer interface (BCI) is to find
      brain patterns, which could easily be detected. One of these pattern is the
      steady-state evoked potential (SSEP). SSEPs induced through the visual sense have
      already been used for brain-computer communication. In this work, a BCI system is
      introduced based on steady-state somatosensory evoked potentials (SSSEPs).
      Transducers have been used for the stimulation of both index fingers using
      tactile stimulation in the "resonance"-like frequency range of the somatosensory
      system. Four subjects participated in the experiments and were trained to
      modulate induced SSSEPs. Two of them learned to modify the patterns in order to
      set up a BCI with an accuracy of between 70% and 80%. Results presented in this
      work give evidence that it is possible to set up a BCI which is based on SSSEPs.

PMID- 16562630
TI  - The effect of random modulation of functional electrical stimulation parameters
      on muscle fatigue.
AB  - Muscle contractions induced by functional electrical stimulation (FES) tend to
      result in rapid muscle fatigue, which greatly limits activities such as FES
      assisted standing and walking. It was hypothesized that muscle fatigue caused by
      FES could be reduced by randomly modulating parameters of the electrical
      stimulus. Seven paraplegic subjects participated in this study. While subjects
      were seated, FES was applied to quadriceps and tibialis anterior muscles
      bilaterally using surface electrodes. The isometric force was measured, and the
      time for the force to drop by 3 dB (fatigue time) and the normalized force-time
      integral (FTI) were determined. Four different modes of FES were applied in
      random order: constant stimulation, randomized frequency (mean 40 Hz), randomized
      current amplitude, and randomized pulsewidth (mean 250 micros). In randomized
      trials, stimulation parameters were stochastically modulated every 100 ms in a
      range of +/-15% using a uniform probability distribution. There was no
      significant difference between the fatigue time measurements for the four modes
      of stimulation. There was also no significant difference in the FTI measurements.
      Therefore, our particular method of stochastic modulation of the stimulation
      parameters, which involved moderate (15%) variations updated every 100 ms and
      centered around 40 Hz, appeared to have no effect on muscle fatigue. There was a
      strong correlation between maximum force measurements and stimulation order,
      which was not apparent in the fatigue time or FTI measurements. It was concluded
      that a 10-min rest period between stimulation trials was insufficient to allow
      full recovery of muscle strength.

PMID- 16562631
TI  - Dynamic modeling and torque estimation of FES-assisted arm-free standing for
      paraplegics.
AB  - This paper presents an application of recent findings in the field of redundant
      robotic systems' control, toward investigating the feasibility of functional
      electrical stimulation (FES) assisted arm-free standing for paraplegics. Twelve
      degrees-of-freedom (DOF) forward and inverse dynamic models of quiet standing
      have been developed. These models were used to investigate the minimum number of
      DOF that would need to be actuated in order to generate stable quiet standing in
      paraplegics despite internal and external disturbances. The results presented
      herein suggest that the proposed nonlinear dynamic model could achieve guaranteed
      asymptotic stability with only six active DOF, assuming that the remaining six
      DOF are passive, i.e., there is no active or passive torques applied to those
      DOF. The stability analyses were performed using a proportional and derivative
      (PD) controller coupled with gravity compensation. The results of this analysis
      suggest that if only six particular DOF are actively controlled in a paraplegic
      subject, this individual should be able to achieve stable quiet standing despite
      disturbances. This result has both clinical and system-design implications for
      the development of a device that will facilitate FES-assisted arm-free quiet
      standing. The clinical implication is, if a paraplegic patient can exert
      voluntary control over specified six DOF in the lower limbs, that patient, after
      intensive physiotherapy, will have the potential to perform quiet standing
      unassisted. The system-design implication is that FES-assisted arm-free standing
      for paraplegics is theoretically plausible if one would actively control only six
      out of 12 DOF in the lower limbs. The proposed solution does not require the
      locking of joints in the lower limbs (commonly applied in the field) or voluntary
      control of the upper body to compensate for the internal and external
      disturbances. Another important finding of this study is the existence of six
      different combinations of six active DOF able to facilitate stable quiet
      standing. This dynamic redundancy of the biological bipedal stance allows the
      selection of an ideal subset of six DOF in designing a neuroprosthesis for
      standing. This further implies that a considerably less complex FES system than
      previously anticipated needs to be developed for FES-assisted standing.

PMID- 16562632
TI  - Adaptive force regulation of muscle strengthening rehabilitation device with
      magnetorheological fluids.
AB  - In rehabilitation from neuromuscular trauma or injury, strengthening exercises
      are often prescribed by physical therapists to recover as much function as
      possible. Strengthening equipment used in clinical settings range from low-cost
      devices, such as sandbag weights or elastic bands to large and expensive isotonic
      and isokinetic devices. The low-cost devices are incapable of measuring strength
      gains and apply resistance based on the lowest level of torque that is produced
      by a muscle group. Resistance that varies with joint angle can be achieved with
      isokinetic devices in which angular velocity is held constant and variable torque
      is generated when the patient attempts to move faster than the device but are
      ineffective if a patient cannot generate torque rapidly. In this paper, we report
      the development of a versatile rehabilitation device that can be used to
      strengthen different muscle groups based on the torque generating capability of
      the muscle that changes with joint angle. The device is low cost, is smaller than
      other commercially available machines, and can be programmed to apply resistance
      that is unique to a particular patient and that will optimize strengthening. The
      core of the device, a damper with smart magnetorheological fluids, provides
      passive exercise force. A digital adaptive control is capable of regulating
      exercise force precisely following the muscle strengthening profile prescribed by
      a physical therapist. The device could be programmed with artificial intelligence
      to dynamically adjust the target force profile to optimize rehabilitation
      effects. The device provides both isometric and isokinetic strength training and
      can be developed into a small, low-cost device that may be capable of providing
      optimal strengthening in the home.

PMID- 16562633
TI  - Neural network-based hybrid human-in-the-loop control for meal assistance
      orthosis.
AB  - In order to assist some elderly and disabled people, who have partly or
      completely lost the ability of moving their upper limbs due to neurological
      disabilities or spinal cord disease, to take meals by themselves independently, a
      new type of meal assistance orthosis was recently developed. This paper presents
      a neural network-based hybrid human-in-the-loop control for this meal assistance
      orthosis with functional and safety purposes. In this approach, the position
      control and the force-free control are integrated into a single controller based
      on the model of meal assistance orthosis. By means of the position control, the
      meal assistance orthosis is controlled to generate appropriate compensation
      forces for assisting the movement of upper limb. In order to reduce the risk of
      hurting the bodies of human end-users and of damaging the device due to the
      impact from large external forces, with the force-free control, the meal
      assistance orthosis can flexibly move with the driven of large external forces.
      In addition, the controller of the meal assistance orthosis can be smoothly
      switched between the position control and the force-free control through a
      designed process to avoid instantaneously generating large external force owing
      to hard switching. In order to improve the adaptability of the proposed approach
      to different subjects, neural networks are adopted in the controller. Moreover,
      the proposed approach fully takes into account the influence of external forces
      induced by upper limb in the control process to form a kind of human-in-the-loop
      control. With the simulation and experiment of the meal assistance orthosis, the
      effectiveness of the proposed method was verified.

PMID- 16562634
TI  - Accessing the influence of repositioning on the pelvis' 3-D orientation in
      wheelchair users.
AB  - This study aimed at evaluating the effects of mechanical repositioning, obtained
      by the increase in seat-to-back (STB) and system tilt angles, on the position of
      the pelvis with spinal-cord injured subjects seated in a wheelchair. The
      noninvasive method used combined magnetic resonance imaging (MRI) images of the
      whole pelvis obtained in a supine posture and ultrasound images of the pelvic
      iliac crests obtained in four seating positions. The matching of the two image
      data sets enabled the location of fourteen pelvic landmarks in the seated
      positions. From these landmarks, the pelvic tilt, obliquity, and transverse
      rotation, and the three-dimensional (3-D) motion of the pelvis were calculated.
      Results showed that the increase in STB angle is not equal to the calculated
      increase in pelvic tilt and that the pelvis rotated posteriorly, moved forward
      and downwards. An increase in the system tilt moved the pelvis rearwards and
      downwards, which counter-balanced the movement seen with the increase in STB. At
      the return to the first position, no significant changes were observed in the
      pelvis' position and orientation compared to the initial posture. Results also
      demonstrated the importance in calculating the total 3-D rotations and
      translations to characterize adequately the pelvic movement.

PMID- 16562635
TI  - Development and qualitative assessment of the GAME(Cycle) exercise system.
AB  - Increased physical activity is important for reducing the risk of cardiovascular
      disease. However, among people with disabilities, inactivity is prevalent. In
      order to encourage exercise among members of this group, an exercise system
      combining arm ergometry with video gaming, called the GAME(Cycle) was previously
      developed. User input was received through an arm crank ergometer on a swivel,
      with the angular velocity of the ergometer resistance wheel controlling one axis
      and rotation of ergometer about the swivel controlling the other. The purpose of
      this study was to detail the algorithms used in this device and present novel
      features included in a second generation of the GAME(Cycle). The features include
      a wheel on base, a steering return mechanism, and wireless fire buttons. A focus
      group of clinicians (n = 8), wheelchair users (n = 8), and clinician wheelchair
      users (n = 2) was conducted to evaluate the features of the GAME(Cycle). The
      focus group suggested improvements to the steering mechanism and to reduce
      vibration in the system. However, the focus group enjoyed the GAME(Cycle) and
      felt that it would encourage exercise among persons with disabilities.

PMID- 16562636
TI  - Evaluation of the stability of intracortical microelectrode arrays.
AB  - In order to use recorded neural activities from the brain as control signals for
      neuroprosthesis devices, it is important to maintain a stable interface between
      chronically implanted microelectrodes and neural tissue. Our previous paper
      introduced a method to quantify the stability of the recording microelectrodes.
      In this paper, the method is refined 1) by incorporating stereotypical behavioral
      patterns into the spike sorting program and 2) by using a classifier based on
      Bayes theorem for assigning the recorded action potentials to the underlying
      neural generators. An improved method for calculating stability index is
      proposed. The results for the stability of microelectrode arrays that differ in
      structure are presented.

PMID- 16562637
TI  - Solutions to electromagnetic interference problems between cochlear implants and
      GSM phones.
AB  - For persons using cochlear implants, electromagnetic compatibility (EMC) problems
      may sometimes be an obstacle to using digital cellular telephones. This study
      aimed at exploring the benefit of three new assistive listening device prototypes
      that eliminate or diminish EMC problems. Ten experienced cochlear implant users
      listened in quiet to running speech samples and a sentence test on a landline
      phone, a digital cellular phone with and without three prototypes. The subjects'
      performance was assessed using a sentence test, a subjective visual analog scale,
      and by ranking the best and the poorest listening condition. Compared to the
      other test conditions, listening to a digital cellular phone alone revealed, on
      average, the poorest sentence recognition scores (29%) and the poorest results in
      four different subjective judgments (the amount of disturbances, the clarity of
      the message, the quality of the sound, overall judgment) with all three implant
      systems tested. The prototypes generally helped the implantees to recognize
      speech better on the cellular telephone (by 10-21 percent units, on average). Use
      of assistive listening devices and further development of EMC of both cochlear
      implant systems and digital cellular phones needs to take place to enable smooth
      use of digital cellular phones for all implantees.

PMID- 16562638
TI  - Neural-electronic inhibition simulated with a neuron model implemented in SPICE.
AB  - There have been numerous studies presented in the literature related to the
      simulation of the interaction between biological neurons and electronic devices.
      A complicating factor associated with these simulations is the algebraic
      complexity involved in implementation. This complication has impeded simulation
      of more involved neural-electronic circuitry and consequently has limited
      potential advancements in the integration of biological neurons with synthetic
      electronics. In this paper, we describe a modification to a previously proposed
      SPICE based Hodgkin-Huxley neuron model that demonstrates more physiologically
      relevant electrical behavior. We utilize this SPICE based neuron model in
      conjunction with an external circuit that allows for artificial selective
      inhibition of neural spiking. The neural firing control scheme proposed herein
      would allow for action potential frequency modulation of neural activity that, if
      developed further, could potentially be applied to suppress undesirable neural
      activity that manifests symptomatically as the tremors or seizures associated
      with specific pathologies of the nervous system.

PMID- 16562639
TI  - An oral tactile interface for blind navigation.
AB  - An oral tactile interface was designed and evaluated to provide directional cues
      through the tactile channel, which may be utilized by a blind traveler to obtain
      directional guidance in outdoor navigation. The device was implemented as a
      mouthpiece with a microfabricated electrotactile display on top for tactile
      presentation onto the roof of the mouth and a tongue touch keypad at the bottom
      for simultaneous operation by the tongue. An experimental system allowed a user
      to communicate with a computer tactilely by using the oral interface. Directional
      cues were presented to the user as line or arrow patterns with four moving
      directions (leftward, rightward, forward, and backward). Electrotactile
      presentation on the roof of the mouth was evaluated in experiments of threshold
      measurement and identification of directional cues. Experimental results from six
      human subjects showed that the roof of the mouth required stimulation intensities
      around 15 V for threshold sensation, and around 25-30 V for comfortable and well
      perceived stimulation. Furthermore, identification of leftward or rightward
      movements was highly accurate while performance on forward or backward moving
      patterns was mixed and varied considerably among subjects.

PMID- 16562640
TI  - [Quality of sleep in hospitalized psychiatric patients].
AB  - To determine the global sleep quality and its components in patients of the
      Psychiatric Hospital of Maracaibo we performed a cross-sectional descriptive
      study based on a personal survey and the application of the Pittsburgh Sleep
      Quality Index (PSQI) in 57 individuals selected among all the 70 patients
      hospitalized in the Psychiatric Hospital of Maracaibo in the month of May of
      2004. 91.22% of the patients displayed alterations of the sleep (slight 28.07%,
      moderate 8.77% and severe 54.38%). Several of the components of the PSQI were
      within acceptable ranks: sleep duration greater to 7 hours in 24 hours (47.36%);
      habitual efficiency of sleep: 0 points in 54.38%; whereas other components
      altered the global PSQI score causing that 91.22% of the people interviewed were
      considered "poor sleepers". These alterations were: Moderate extrinsic
      disturbances of the sleep observed in 50.87% of the patients, hypnotic medication
      taken by 84.21%, and severe diurnal dysfunction detected in 42.10% of the studied
      population. The main diagnostic categories on admission were: Schizophrenia 21
      patients, classified as follows: Residual Schizophrenia, 10 patients; Paranoid
      Schizophrenia, 10 patients; Undifferentiated Schizophrenia, 1 patient. Of the 21
      schizophrenic patients only 1 was diagnosed as a "good sleeper"; 11 patients with
      Bipolar I Disorders, whose most recent episode was mania with Psychotic symptoms,
      4 were described as "good sleepers", and 7 as "poor sleepers". Psychotic
      alterations induced by alcohol with delirious ideas: 6 patients, all "poor
      sleepers". Three ranks of ages were distinguished that included most of the
      population studied: the patients 34 to 39 years of age (12) were "poor sleepers";
      of those aged 28 to 33 years (11) only 1 patient was described as "good sleeper",
      and of those 22 to 27 years of age (11) only 2 patients were described as "good
      sleepers". In conclusion, an association between mental disease and the
      deterioration of the quality of the sleep was detected, being the latency of the
      sleep and the use of hypnotic medication the main components of this impairment.

PMID- 16562641
TI  - [Serotype profile and antibiotyping of Streptococcus pneumoniae strains isolated
      from nasal carriage in pediatric patients].
AB  - The aim of this study was to determine the serotype profile and antibiotyping of
      Streptococcus pneumoniae from nasal isolates in children. Nasopharyngeal swab
      samples obtained from 125 children were cultivated and screened for the presence
      of S. pneumoniae. Strains were identified according to standard microbiological
      methods. The isolates were serotyped by the Quellung reaction and resistance
      patterns were determined by the microdilution method according to NCCLS
      guidelines. Results indicate an overall pneumococcal carriage rate of 24% (n =
      30). The most commonly isolated serotypes were 23F (20%), 6B (20%) and 14 (13%).
      73% of isolates were resistant at least to one of the tested antibiotics. 47% of
      the strains were consistently resistant to penicillin and the serotypes 6B and
      23F were frequently associated with this marker. 60% of the strains were
      resistant to doxycycline, 37% to trimethoprim/sulfamethoxazole and clindamycin,
      30% to erythromycin, 23% to cloramphenicol, 7% to ceftriaxone and 3% to cefepime.
      All strains were sensible to ofloxacin, rifampin and vancomycin. The most common
      combined resistance patterns were PNC-ERI-TMP/SMX-DOX-CLO-CLI (16.59%) and PNC
      DOX (13.27%). The results obtained in this study will allow to orient the empiric
      therapy for pneumococcal infections and a rational use of antibiotics in clinical
      practice, as well as the application of an appropriate vaccination program
      specially adapted to the serotypes more frequently found in children.

PMID- 16562642
TI  - High prevalence of secondary resistance mutations in Venezuelan HIV-1 isolates.
AB  - The genetic variability was studied in HIV-1 from Venezuelan patients with and
      without treatment, in order to evaluate the presence of polymorphisms and drug
      resistance mutations. Proviral DNA from peripheral blood mononuclear cells or
      viral RNA from plasma was extracted from the blood of 30 patients. Two regions
      from the polymerase gene, protease (Pr) and reverse transcriptase (RT) and one
      genomic fragment from the envelope (Env) gene were amplified and sequenced. All
      HIV-1 samples analyzed were classified as subtype B, without evidence of
      recombination. Although no primary protease mutations were detected, a high
      frequency of secondary mutations (86%, 19/22), associated to restoration of viral
      replicative fitness, was observed in strains circulating both in treated and non
      treated patients. Resistance mutations to nucleoside RT inhibitors (NRTI) and non
      nucleoside RT inhibitors (NNRTI) were detected in 35% (6/17) and 12% (2/17) of
      the viruses circulating in treated patients, respectively. Resistance mutations
      were also present in the virus infecting one antiretroviral naive individual
      (7.7%), suggesting that local screening for resistant mutation in naive patient
      might be important to minimize therapy failure. Future studies are warranted to
      assess the role of secondary mutation in the success of viral infection.

PMID- 16562643
TI  - [Changes in serum lipids, plasma fibrinogen and other haemostatic parameters
      induced by ciprofibrate action in hyperlipidemic patients with and without
      coronary artery disease].
AB  - The effects of drugs with hypolipidemic properties in the prevention of the
      atherothrombotic vascular disease, go further than reducing serum lipids,
      suggesting that there are other nonlipid-related mechanisms involved; the
      maintenance of appropriate haemostatic balance being one of them. The objective
      of this investigation was a drug intervention with ciprofibrat in hyperlipidemic
      people with high level of plasmatic fibrinogen with the purpose of knowing the
      effects of the drug over these risk factors and other haemostatic parameters.
      Forty people, both sexes, 20 of them apparently healthy and the other 20 with
      clinical and angiographic evidence of coronary artery disease, were randomized to
      receive 100 mg of ciprofibrat or placebo during an average of 56 weeks. All of
      them had a clinical exam, EKG and stress test. Laboratory exams included lipid
      profile, plasma fibrinogen (Fg), VII factor, vonWillebrand factor, protein C (PC)
      and the tissue plasminogen activator with samples taken every 8 weeks. The
      Ciprofibrat group showed significant changes of lipids: cholesterol -23%,
      triglycerides -31%, high-density lipoprotein (HDLc) +24% and very low-density
      lipoprotein -23%, except low-density lipoprotein -24%. The haemostatic parameters
      in 40 weeks showed that Fg decreased 21% (p = 0.001), decreasing to 9% at the end
      of the follow-up. In the placebo group the HDLc showed a 10% increase (p = 0.02),
      PC reduced to 20% (p = 0.01) and Fg kept blood levels close to basal line,
      descending 10% at the end of the follow-up. In this study, the use of ciprofibrat
      in patients with high risk of developing atherothrombotic events, showed
      efficiency and security in handling hyperlipidemia, such as keeping and
      appropriate haemostatic balance.

PMID- 16562644
TI  - [Effect of using several levels of positive end-expiratory pressure over
      barotrauma's induced lung injury in a model of isolated and perfused rabbit
      lungs].
AB  - The use of Positive end-expiratory pressure (PEEP) as a strategy of mechanical
      ventilation offers its advantages, such as improved oxygenation, without causing
      alveolar overstretching and barotrauma. We aim to investigate the effect of
      several levels of PEEP on barotrauma and, whether an optimal level of PEEP
      exists. Forty-eight New Zealand rabbits (2.5-3.5 kg) were divided into four
      groups with PEEP settings of 0, 4, 8 and 12 cmH2O, at increasing levels of
      inspiratory volume (IV). This was done in blood perfused rabbit lungs and in
      lungs perfused with a Buffer-Albumin Solution. We observed that lungs ventilated
      with PEEP 0 cmH2O suffered pulmonary rupture at high IV (300cc), with significant
      increases of Pap (Pulmonary artery pressure) and FFR (Fluid filtration rate).
      Lungs ventilated with PEEP 8 and 12 suffered pulmonary rupture at lower IV (200cc
      and 150cc vs. 300cc respectively) On the other hand, lungs ventilated with PEEP 4
      cmH2O reached the highest IV (400cc), in addition, they showed the lowest
      elevations of Pap and FFR. The acellular lungs ventilated with PEEP 4, 8 and 12
      showed pulmonary rupture at lower IV when compared with cellular ones (300cc vs.
      400cc: 100cc vs. 200cc and 100cc vs. 150cc respectively). We concluded that an
      optimal PEEP exists, which protects against barotrauma, however, excess of PEEP
      could enhance its development. The blood could contain some mediators which
      attenuate the damage induced by barotrauma.

PMID- 16562645
TI  - [Fixed pigmented erythema related to the oral administration of carbamazepine:
      report of one case].
AB  - Carbamazepine (CBZ) is an oral anticonvulsant drug, structurally similar to
      tricyclic antidepressants. It is preferred over other drugs because it has fewer
      adverse effects on behavior and alertness. However, hematologic toxicity is
      possible during therapy with CBZ. Patients should undergo routine monitoring of
      hematologic function. CBZ can make the skin more sensitive to the sun or
      ultraviolet light, therefore, dermatological effects of this drug also can happen
      such as, skin rash, urticaria, and erythema multiforme. The present study reports
      the case of a female patient that presented hyperchromic-concentric-pruriginous-
      spots on the skin of her hands after six months of treatment with CBZ. She came
      to the physicians of the Clinical Pharmacokinetic Service (Laboratory of
      Toxicology of IAHULA, Merida-Venezuela) requesting a drug monitoring. The results
      showed a level of 8.51 microg x. mL(-1), which was found within the therapeutic
      range (4-12 microg x mL(-1)). Subsequently, the dermatologist diagnosed fixed
      pigmented erythema related to the ingestion of a specific medication which began
      disappearing after 15 days of CBZ free-treatment and with the aid of a
      dermatologic formulation.

PMID- 16562646
TI  - [Immune evasion mechanisms of hepatitis C virus. Review].
AB  - Hepatitis Virus C (HCV) is a major worldwide health care problem. HCV infection
      usually tends to become chronic and can generate long-term hepatic cirrhosis and
      hepatocellular carcinoma. These affections frequently require a liver transplant
      to prolong the patients life. Maintenance of the chronic infection implies
      evasion of the host immune responses. Viral mechanisms involved in this evasion
      are being profusely studied in order to develop new and effective therapies and
      vaccines against HCV. An important HCV characteristic, its high genetic
      variability, has been proposed to contribute to immune evasion by means of
      antigenic change and variation. On the other hand, some studies suggest that
      genetic variability is not necessary to establish a chronic infection. Other
      studies related to immune responses in patients with spontaneous virus clearance
      and patients with chronic infection show a possible immunosuppression caused by
      some viral proteins, that may be essential to persist in the host. Specifically,
      it is believed that viral proteins NS5A, E2 and Core modulate some innate and
      specific immune mechanisms. The analysis of all data related to this topic
      suggests the existence of synergistic cooperation between viral variation and
      immunosuppression to overcome the immune defenses of the host.

PMID- 16562647
TI  - [Pattern of T cell activation in absence of protective immunity against hepatitis
      B virus. Review].
AB  - Hepatitis B is an important cause of morbidity and mortality around the world.
      One-third of the world's population has been estimated to be infected with
      hepatitis B virus (HBV). A significant amount of evidence suggests that both
      humoral and cellular immune responses are important to eliminate the virus and
      that, cellular immunity is involved in the pathogenesis of the disease.
      Vaccination with HBsAg is considered as the main strategy for effective control
      of the infection and viral transmission. However, approximately 5-10% of
      immunized individuals fail to elicit detectable specific antibodies and remain at
      risk for hepatitis B infection. In this work we have reviewed the current status
      in the pathogenesis of the disease and the mechanisms described to explain
      nonresponsiveness to the vaccine as well. Since nonresponders to the vaccine are
      at risk for the infection, a common mechanism to explain the absence or
      inappropriate immune response to virus components is proposed. Within the
      suggested model an impaired activation of T lymphocytes against viral antigens,
      both in nonresponders to vaccination and chronically infected patients, is
      described. These observations could be consistent with potential differences in
      the MHC/Ag presentation; therefore contributing to our understanding of the
      altered T helper response as an underlying mechanism for the lack of protective
      immunity against VHB.

PMID- 16562648
TI  - Management of cancer in the elderly.
AB  - With the aging of the Western population, cancer in the older person is becoming
      increasingly common. After considering the relatively brief history of geriatric
      oncology, this article explores the causes and clinical implications of the
      association between cancer and aging. Age is a risk factor for cancer due to the
      duration of carcinogenesis, the vulnerability of aging tissues to environmental
      carcinogens, and other bodily changes that favor the development and the growth
      of cancer. Age may also influence cancer biology: Some tumors become more
      aggressive (ovarian cancer) and others, more indolent (breast cancer) with aging.
      Aging implies a reduced life expectancy and limited tolerance to stress. A
      comprehensive geriatric assessment (CGA) indicates which patients are more likely
      to benefit from cytotoxic treatment. Some physiologic changes (including reduced
      glomerular filtration rate, increased susceptibility to myelotoxicity, mucositis,
      and cardiac and neurotoxicity) are common in persons aged 65 years and older. The
      administration of chemotherapy to older cancer patients involves adjustment of
      the dose to renal function, prophylactic use of myelopoietic growth factors,
      maintenance of hemoglobin levels around 12 g/dL, and proper drug selection. Age
      is not a contraindication to cancer treatment: With appropriate caution, older
      individuals may benefit from cytotoxic chemotherapy to the same extent as the
      youngest patients.

PMID- 16562649
TI  - Targeting the epidermal growth factor receptor. Trials in head and neck and lung
      cancer.
AB  - The epidermal growth factor receptor (EGFR) promotes the growth of different cell
      types and has been implicated in tumorigenesis. The EGFR comprises a family of
      four structurally similar tyrosine kinases with a complex link to downstream
      signaling molecules that ultimately regulate key cell processes. Anti-EGFR agents
      have been developed as promising therapeutic anticancer targets, and some have
      been recently approved for the treatment of non-small-cell lung cancer and colon
      cancer. The two anti-EGFR therapies with the greatest clinical application are
      monoclonal antibodies that block the binding of ligands to EGFR and small
      molecule tyrosine kinase inhibitors that inhibit the binding of adenosine
      triphosphate to the internal tyrosine kinase receptor of EGFR. We attempt to give
      an overview of the EGFR function and biology, focusing on the most important
      clinical findings and applications of EGFR inhibitors in lung and head and neck
      cancer.

PMID- 16562650
TI  - Radiation therapy for resectable colon cancer. Is there a role in the modern
      chemotherapy era?
AB  - Colon cancer is a major public health problem. The primary treatment is
      resection. For patients with early-stage disease, surgery results in excellent
      survival rates. In contrast, patients with locally advanced tumors arising in
      "anatomically immobile" segments of large bowel have a less satisfactory outcome,
      in part secondary to compromised surgical clearance. Patterns-of-failure analyses
      suggest that for tumors that invade adjacent organs, exhibit perforation or
      fistula, or are subtotally resected, local failure rates exceed 30%. Multiple
      single-institution retrospective studies have shown improved local control and
      possibly survival with the addition of external irradiation and/or intraoperative
      radiation. In contrast, a recent Intergroup trial failed to show any benefit by
      the addition of adjuvant radiation therapy combined with chemotherapy.
      Interpretation of this trial's results is handicapped by low patient accrual.
      With the advent of novel and more effective systemic therapies for metastatic
      colon cancer, current and future clinical research will address the efficacy of
      these agents in the adjuvant setting. Adjuvant radiation therapy should be
      considered in patients with colon cancer at high risk for local failure.

PMID- 16562651
TI  - Retroperitoneal neuroblastoma causing urinary obstruction in a 5-month-old boy.

PMID- 16562652
TI  - Holistic tensions: is West really best?

PMID- 16562653
TI  - Integrating complementary therapies.

PMID- 16562654
TI  - Late for a very important date.

PMID- 16562655
TI  - That loving touch.
AB  - Early massage and positive touch in pregnancy can play a big part in helping to
      build closeness within a family group. I have witnessed an increasing number of
      dads bringing their babies to baby massage classes--but the power of positive
      touch can and should start long before that. If the father is encouraged to
      connect with his baby throughout the pregnancy using positive touch and simple
      massage, as their baby grows the mother, father and baby will all benefit.

PMID- 16562656
TI  - Hypnosis: removing the labour from birth.
AB  - Hypnosis has been used in obstetrics for more than a century. However, with
      increasing numbers of women looking for alternative coping strategies for use
      during labour, the birth of a new discipline, HypnoBirthing, is gaining in
      popularity. HypnoBirthing is a hypnotherapy programme specifically designed for
      birth, employing the principles and techniques of hypnosis and self-relaxation.
      This article explains the philosophy and principles of HypnoBirthing, the
      evidence base and its physiological impact on labouring women, brought to life by
      real accounts.

PMID- 16562657
TI  - Shiatsu--an ancient art.

PMID- 16562658
TI  - Aromatherapy massage: an essential service?

PMID- 16562659
TI  - Effective breastfeeding support--an impetus to act.

PMID- 16562660
TI  - Vaginal examination in labour.

PMID- 16562661
TI  - Be prepared.

PMID- 16562662
TI  - Bring back the bed bath!

PMID- 16562663
TI  - Mother mine.

PMID- 16562664
TI  - [Construction of recombinant plasmid pIRES2-EGFP/CCK and its expression in vivo
      and in vitro].
AB  - OBJECTIVE: To construct eukaryotic expression plasmid of porcine CCK gene pIRES2
      EGFP/CCK and express it in COS-7 cells and hamsters. Methods The aimed segments
      were obtained from intermediate vector pMD18-T/CCK and were inserted into an
      eukaryotic expression plasmid pIRES2-EGFP to construct a recombinant expression
      plasmid pIRES2-EGFP/CCK. The recombinant expression plasmid was transfected into
      COS-7 cells by liposome-mediated gene transfer method and was observed through
      fluorescence microscope. The plasmid was injected into the skeletal muscle of
      hamsters directly to detect the expression of the recombinant plasmid in vivo.
      RESULTS: A recombinant eukaryotic expression plasmid pIRES2-EGFP/CCK was
      successfully constructed. Green fluorescent protein could be detected in the
      transfected COS-7 cells 24, 48, and 72 hours after the transfection. On the 4th
      day postinjection into the skeletal muscle of hamsters, the protein could be
      detected at the injection site and the fluorescence intensity became much
      stronger on the 14th day than that on the 4th day. On the 42nd day the protein
      level increased. The green fluorescence protein was never expressed in the
      untransfected cells. CONCLUSION: The porcine CCK gene eukaryotic expression
      plasmid pIRES2-EGFP/CCK is constructed successfully, and is expressed in mammal
      COS-7 cells and hamsters in vivo. The research paves the way for the cross
      immunity therapy of hamster pancreatic carcinoma.

PMID- 16562665
TI  - [Biotoxicology and biodynamics of silica nanoparticle].
AB  - OBJECTIVE: To investigate the toxicology and biodynamics of silica nanoparticle.
      METHODS: The silica nanoparticles were injected into mice through tail vein, and
      the mice were amphimixised, the urine was collected in different time, variations
      of pathology in organs and tissues of the mice were detected. At the same time,
      the silica nanoparticles' distribution in the tissues was observed through
      electron microscope. RESULTS: The silica nanoparticles were detected in all
      tissues and urine of the mice. The injected mice can reproduce as normal.
      CONCLUSION: The silica nanoparticles do not have toxicity and can be used in
      vivo.

PMID- 16562666
TI  - [Identification and clone of human Alzheimer's disease related gene nicastrin
      promoter].
AB  - OBJECTIVE: To identify the promoter of human nicastrin (NCT) gene, a major
      component of gamma-secretase which is closely related with pathogenesis of
      Alzheimer's disease. METHODS: Promoter of human Alzheimer's disease related gene,
      nicastrin, a 1768 bp fragment was firstly isolated from human genomic DNA by PCR.
      This fragment's 3 flanking end was 4 bp upstream to the start codon ATG (+1) of
      the gene. This fragment was used as template, a series of deleted fragments were
      amplified and constructed to the pGL3-Enhancer plasmid with the artificial
      designed linkers. The relative activity of their promoter in Hela cells was
      studied by dual-luciferase assay. RESULTS: The 420 bp fragment showed the
      strongest activity, and the 237 bp fragment was the minimal fragment in length
      with activity. CONCLUSION: The promoter of NCT is located at -432/-133 region
      upstream the translational start codon, while its basal promoter is between -359/
      90 that drives the transcription of reporter gene in Hela cells.

PMID- 16562667
TI  - [Apoptosis of mesenchymal cell line MBA-1 induced by core binding factor alpha
      1].
AB  - OBJECTIVE: To investigate the effect of two core binding factors alpha 1 (Cbfa1)
      isfroms (Cbfa1/P56 and Cbfa1/P57) on the apoptosis of mesenchymal cell line MBA
      1. METHODS: The two Cbfal isfroms were transiently transfected into MBA-1 cells,
      then the changes of apoptosis rate were observed by flow cytometer. The protein
      expressions of Cbfa1, Bax, Bcl-2, caspase-3, and caspase-9, cytochrome-C and TNF
      alpha were determined by Western immunoblot. RESULTS: After the transient
      transfection with the two isforms of Cbfa1, MBA-1, the cells apoptotic rates
      increased, and the ratio of Bax/Bcl-2, the expressions of cytochrome-C, caspase
      3, caspase-9, and TNF-alpha were significantly increased. CONCLUSION: Cbfa1 can
      promote the apoptosis in mesenchymal cell line MBA-1. Bax/Bcl-2, cytochrome-C,
      caspase-9, caspase-3, and TNF-alpha are also involved in the apoptosis pathway.

PMID- 16562668
TI  - [Transduction efficiency of recombinant adeno-associated virus 2 in human bone
      marrow CD34+ hematopoietic stem/progenitor cells and mesenchyme stem cells].
AB  - OBJECTIVE: To investigate the transduction efficiency of recombinant adeno
      associated virus 2 ( rAAV2) in human bone marrow CD34+ hematopoietic
      stem/progenitor cells and mesenchyme stem cells. METHODS: The rAAV2 containing
      green fluorescent protein genes (rAAV2/GFP) were constructed, packaged and
      purified. CD34+ hematopoietic stem/progenitor cells and mesenchyme stem cells
      were infected with the rAAV2/GFP. After transduction for 48 hours, the expression
      of GFP was detected under fluorescence microscope. Furthermore, the transduction
      efficiency of AAV transduced CD34+ with hydroxyurea (HU) pretreatment and that of
      untreated were compared. RESULTS: GFP genes were expressed in 5.3% +/- 1.7% CD34+
      cells. After pretreatment with HU, the expression of the GFP gene in CD34+ cells
      increased to 13.2% +/- 2.8%, and 23% +/- 3.6% mesenchyme stem cells expressed the
      GFP gene. Conclusion The transduction efficiency of mesenchyme stem cells is
      higher than that of CD34+ hematopoietic stem/progenitor cells. HU pretreatment
      can obviously increase the transduction efficiency of CD34+ hematopoietic
      stem/progenitor cells.

PMID- 16562669
TI  - [Effect of realgar on the gene expression profile of multiple myeloma cell line
      RPMI 8226].
AB  - OBJECTIVE: To explore the effect of realgar on the gene expression profiles of
      multiple myeloma cell line RPMI 8226 by apply cDNA microarray. METHODS: The gene
      expression of RPMI 8226 cells before and after 48 hours of realgar treatment was
      determined with a cDNA microarray representing 4096 human genes. RESULTS: At the
      mRNA level, 164 genes were differentially altered; 53 genes were up-regulated;
      and 111 genes were down-regulated. CONCLUSION: The realgar treatment to RPMI 8226
      cell line may induce a number of gene changes. Many genes may be involved in the
      pathogenesis of multiple myeloma. BTG1, ALK1, and TXNIP genes may play an
      important role in the apoptosis and differentiation of RPMI 8226 cells.

PMID- 16562670
TI  - [GPI-PLD gene exon14 polymorphisms of leucocyte in peripheral blood from healthy
      persons and leukemia patients].
AB  - OBJECTIVE: To analyze the polymorphisms of glycosylphosphatidylinositol-specific
      phospholipase D (GPI-PLD) gene exon 14, GPI-PLD activity of leucocyte in the
      peripheral blood,and the relationship in leukemia patients of Han nationality in
      Hunan. METHODS: Both 96 leukemia patients and 96 healthy persons of Han
      nationality in Hunan were researched [including 48 acute non-lymphocytic
      leukaemia (ANLL) patients as group A, 31 acute lymphoblastic leukaemia (ALL)
      patients as group B, 12 chronic granulocytic leukaemia (CML) patients as group C,
      5 chronic lymphocytic leukaemia (CLL) patients as group D]. The polymorphisms
      were analyzed by PCR-SSCP and sequencing;. and GPI-PLD activities were determined
      by GPI-anchored placental alkaline phosphatase (PLAP) as substrate and triton
      X114 partioning. RESULTS: There were four variations in the coverage of GPI-PLD
      gene exon 14 of leukemia patients and healthy persons. The codons of variation
      were: 1257 C-->T, 1298 T-->C, 1218 C-->A, 1257 C-->A. The total various frequency
      in leukemia patient and healthy person, which was determined by SSCP, was 28.12%
      and 20.83%. On the basis of the percentage of GPI-anchored PLAP conversion, the
      leucocyte GPI-PLD activities of the 96 leukemia patients were measured. Compared
      with the 96 healthy controls, the leukocyte GPI-PLD activites of ANLL and CLL
      patients were significantly increased; the acticities of ALL and CML patients
      were significantly reduced. CONCLUSION: Leukocyte GPI-PLD gene in the peripheral
      blood, which belongs to healthy persons and leukemia patients of Han nationality
      in Hunan, is polymorphism. The leukocyte GPI-PLD activities in the four groups
      are remarkable.

PMID- 16562671
TI  - [Effects of GM-CSF on the proliferation and activation of dendritic cells in
      vivo].
AB  - OBJECTIVE: To explore the effects of granulocyte macrophage-colony-stimulating
      factor (GM-CSF) on the proliferation and activation of dendritic cells (DC) in
      vivo. METHODS: Balb/c mice were randomly assigned into the control and GM-CSF
      treatment group. After the lethal dosage of irridiation, green fluorescence
      protein labelled hematopoietic stem cells (HSC) were injected into the tail veins
      of the mice. The dosage of 0.1 micorg GM-CSF was administer subcutaneously every
      2 days after the HSC infusion. The numbers and activation status of splenic DC
      were observed by flow cytometry 1, 2, 3, and 4 weeks after the HSC
      transplantation. RESULTS: The numbers of splenic DC in the GM-CSF treatment group
      were significantly higher than those of the control group. The expressions of
      surface marker CD40, CD80, and CD86 in the GM-CSF treatment group were also
      higher than those of the control group. CONCLUSION: GM-CSF can enhance the
      proliferation and activation of DC in vivo.

PMID- 16562672
TI  - [Lymphangiogenes and location of tumor lymphatic vessels induced by VEGF-C in
      primary breast carcer].
AB  - OBJECTIVE: To investigate the lymphangiogenesis and location of tumor lymphatic
      vessels induced by vascular endothelial growth factor C (VEGF-C) in primary
      breast cancer. METHODS: The expression of VEGF-C mRNA in 89 cases of primary
      breast cancer was detected by in situ hybridization, and lymphatic vessels with
      vascular endothelial growth factor receptor-3 (VEGFR-3) were labeled by
      immunohistochemistry SP method. RESULTS: VEGF-C mRNA expressed in 49 of all 89
      cases of primary breast cancer, and the expression rate was 55.06%. The
      expression of VEGF-C mRNA was positively correlated with lymphatic vessel density
      (LVD) and axillary lymph node metastasis, LVD and the rate of axillary lymph node
      metastasis were significantly higher in VEGF-C mRNA positive group than those in
      the negative group (both P < 0.05). Different levels of lymphangiogenesis took
      place in all cases of breast cancer, but it was mainly located in tumor stroma,
      and apparently mature lymphatic vessels were not found in cancer nests. LVD was
      positive related with the clinical stage and axillary lymph node metastasis in
      breast cancer; the clinical stage, the LVD, the axillary lymph node metastasis in
      positive group were higher than those in the negative group (P < 0.05).
      CONCLUSION: The expression of VEGF-C mRNA is positively correlated with
      lymphangiogenesis and axillary lymph node metastasis in primary breast cancer.
      Lymphangiogenesis induced by VEGF-C predominantly takes place in the tumor stroma
      tissue, and mature lymphatic vessels are not found in cancer nests.

PMID- 16562673
TI  - [Screening for proteins interacting with ataxin-3, the gene product of SCA3/MJD].
AB  - OBJECTIVE: To screen for proteins interacting with ataxin-3 by yeast two-hybrid
      system 3, and to discuss the function of ataxin-3 and pathogenesis of
      spinocerebellar ataxia type 3 and Machado-Joseph disease (SCA3/MJD). METHODS:
      First we sub-cloned the full reading frame of both wild-type and mutant ataxin-3
      into carrier pGBKT7 (ataxin-3-bait), and then screened human brain cDNA library
      with ataxin-3-bait. RESULTS: We found five positive clones in 6.5 x 10(6)
      transformers. After sequencing, we knew all of them were novel ataxin-3
      interacting proteins. Three were corresponded to the known sequences coding the
      known proteins, which were human Rho GDP dissociation inhibitor alpha, small
      ubiquitin-like modifier 1, and human neuronal amiloride-sensitive cation channel
      2. Another two of the five were unknown. CONCLUSION: Small ubiquitin-like
      modifier 1 probably interacted with ataxin-3, suggesting that the sumoylation
      probably participated in post-translation modifying of ataxin-3 and pathogenesis
      of SCA3/MJD.

PMID- 16562674
TI  - [Correlation research between cancer stem cells and the pathological grades of
      neuroepithelial tumors].
AB  - OBJECTIVE: To explore the methods of isolation, culture and identification of
      brain tumor stem cells (BTSCs) in neuroepithelial tumor tissues in vitro, and to
      study the correlation between BTSCs and the patholorical grades of
      neuroepithelial tumors. METHODS: Tumor cells from patients undergoing
      neuroepithelial tumors excision were acutely dissociated, triturated into single
      cells, and then seeded into serum-free medium. After the primary brain tumor
      spheres (BTSs) were generated, they were triturated again and passaged in fresh
      medium. The expression of Nestin and CD133 of BTSs was detected by
      immunocytochemistry staining, and the expression of CD133 of tumor specimen
      sections was detected by immunohistochemistry staining . The expression of CD133
      of 46 brain tumors and 5 normal brain tissues were analysed by SABC
      immunohistochemical staining, and the correlation between the expression and
      pathological grade of the tumors was analysed. RESULTS: BTSCs from
      neuroepithelial tumors could be isolated and cultured, and could be generated and
      passaged in vitro. The expression of Nestin and CD133 could be detected in BTSCs.
      CD133 could be detected in neuroepithelial tumor tissues, but not in normal brain
      tissues. There was significant difference between the expression of CD133 and the
      different grades of tumors (P < 0.01), and there was a positive correlation
      between the expression of CD133 and the histologic grading of tumors (P < 0.01).
      CONCLUSION: A small proportion of stem cells have the ability to self-renew in
      human neuroepithelial tumors, and there is a positive correlation between the
      expression of CD133 and histologic grading of tumors.

PMID- 16562675
TI  - [Expression of NMDA receptor-1 induced by NMDA in the brain of neonatal SD rats].
AB  - OBJECTIVE: To determine the regulation of the expression of NMDA receptor-1
      induced by NMDA in the brain of neonatal SD rats. METHODS: Neonatal SD rats
      (n=90) were randomly divided into normal control (n=6) and NMDA injected group
      (subdivided into 10 nmol-0 min, 15 min, 30 min, 1 h, 2 h, 4 h groups, and 10, 20,
      50 nmol groups, each n=6). NMDA fluorescent inmmunohistological staining and TTC
      (2,3,5-triphenyltetrazoliun chloride) staining techniques were used. RESULTS: At
      30 min after the injection of 10 nmol NMDA, a few NR1 positive cells could be
      observed along the injection tract. At 1 h after the injection, NR1 positive
      cells in large quantity could be observed in the hippocampal CA1 region and
      paraventricular thalamus of the ipsilateral hemisphere. The number and location
      of positive cells at 2 h and 4 h after the injection were not much different from
      that at 1 h after the injection. At 2 h after injection, stronger NR1 expression
      was observed in the 50 nmol injection group. In addition, slight crinkle of the
      cell wall with mild condensation of the nuclei was also observed in the 50 nmol
      injection group. At 2 h after the injection, no abnormality was observed in 10,
      20, or 50 nmol group after TTC staining. CONCLUSION: The NR1 induced by NMDA is
      expressed in a time-dependent and dose-dependent pattern after a short period of
      "delay", providing a possible "therapeutic window" for using NMDA receptor
      antagonist to treat diseases relating to the NMDA receptor activation.

PMID- 16562676
TI  - [Effect of yizhi jiannao granule on the behavior and neuron apoptosis in SAMP/8
      mice].
AB  - OBJECTIVE: To investigate the effect of yizhi jiannao granule concentration fluid
      (YCF) on the behavior, the apoptosis rate of hippocampus neuron and the
      expression of apoptosis gene Bcl-2, Bax in senescence accelerated mice Senile
      Prone/8 (SAMP/8), and to discuss some mechanism of traditional chinese medicine
      YCF in improving the capability of learning and memory. METHODS: Forty 6-month
      old SAMP/8 mice were randomly divided into the old group, huperzine A (Hup-A)
      group and YCF group. Ten 4-month old SAMP/8 mice were served as a young control
      group. Four groups were given different drugs for 8 weeks, their behavior changes
      were observed, and the hippocampus were taken out to examine the apotosis rate by
      flow cytomeutry (FCM) and the expression of Bcl-2, Bax mRNA by RT-PCR. RESULTS:
      In the YCF group, the escape latency was significantly shortened, the time of
      swim in the platform quadrant significantly increased, the apoptosis rate of
      hippocampus neural decreased; the level of Bcl-2 mRNA and the rate of Bcl-2/Bax
      increased, and the level of Bax mRNA decreased. CONCLUSION: Yizhi jiannao granule
      can decrease the neuron apoptosis rate and the Bax level, increase the Bcl-2
      level, and modulate the rate of Bcl-2/Bax in SAMP/8 brain, which is probably part
      of the mechanisms of inhibiting the apoptosis and improving learning and memory.

PMID- 16562677
TI  - [Effect of naoling decoction on the behavior and the mRNA expression of beta
      amyloid precursor protein in the hippocampus in rats with Alzheimer's disease].
AB  - OBJECTIVE: To observe the effect of naoling decoction (NLD) on the behavior and
      the mRNA expression of beta-amyloid precursor protein (APP) in the hippocampus in
      rat model with Alzheimer's disease (AD). METHODS: D-galactose was intra
      abdominally injected and AlCl3was hypodermically injected to build the AD models.
      The behavior of rats was measured by gamma-electric maze and the level of APP
      mRNA in the model rat hippocampus was observed by RT-PCR. RESULTS: The learning
      and memory capacity in the NLD group was improved and the APP mRNA expression
      level was significantly lower in the NLD group compared with the untreated model
      and the control group (All P < 0.05). CONCLUSION: NLD can lower the expression of
      APP mRNA to reduce beta-amyloid protein deposition of rat hippocampus, which may
      be one of the mechanisms of improving the learning and memory capacity of AD
      model rats.

PMID- 16562678
TI  - [Expression of eNOS in the endothelial cells during the arteriogenesis of pig
      hind-limbs].
AB  - OBJECTIVE: To detect the expression and activity of eNOS during the
      arteriogenesis of hind-limbs of pigs. METHODS: The right femoral artery was
      ligated, and the left femoral artery shamly operated under routine surgical
      procedures. Animals were sacrificed after two weeks. The expression and activity
      of eNOS in collateral vessels were studied by confocal immunofluorescence with
      antibodies against eNOS and phosphorylated eNOS (P-eNOS) respectively. RESULTS:
      In normal small arteries, the expression of eNOS was very low, and the staining
      was very weak. In growing collateral vessels, the expression of eNOS was
      significantly up-regulated, showing very strong positive staining. The expression
      of P-eNOS was also high. Dural immunostaining showed that eNOS and P-eNOS were
      colocalized in the endothelial cells. CONCLUSION: eNOS is up-regulated and
      activated during arteriogenesis, suggesting that eNOS can exert the possible role
      in mediating the proliferation of endothelial cells and the inflammation, and
      contribute to the collateral vessel growth.

PMID- 16562679
TI  - [Protective effect of losartan on injury induced by ox-LDL in endothelial cells
      and the relationship with asymmetric dimethylarginine].
AB  - OBJECTIVE: To investigate the protective effect of losartan against on injury
      induced by ox-LDL in endothelial cells and the relationship with asymmetric
      dimethylarginine (ADMA). METHODS: Endothelial injury was induced by incubation
      with ox-LDL 100 mg/L in cultured HUVECs for 24 h, and the levels of ADMA, lactate
      dehydrogenase (LDH), nitric oxide (NO) and tumor necrosis factor-alpha (TNF
      alpha) in the conditioned medium were measured. The activity of dimethylarginine
      dimethylaminohydrolase (DDAH) of cultured endothelial cells was also determined.
      RESULTS: Incubation of endothelial cells with ox-LDL 100 mg/L for 24 h induced a
      marked elevation of the levels of ADMA, LDH and TNF-alpha in the conditioned
      medium and a significant decrease in the activity of DDAH and the content of NO
      (P < 0.05). Pretreatment with losartan (10(-8) - 10(-6) mmol/L) significantly
      inhibited the increased levels of ADMA, LDH and TNF-alpha, attenuated the
      decreased levels of NO and the decreased activity of DDAH induced by ox-LDL (P <
      0.05). CONCLUSION: Losartan may preserve ox-LDL-induced endothelial cell injury
      by increasing the DDAH activity and decreasing the ADMA level.

PMID- 16562680
TI  - [Expressions of TGIF, MMP9 and VEGF proteins and their clinicopathological
      relationship in gastric cancer].
AB  - OBJECTIVE: To detect the expressions of TG-interacting factor (TGIF), matrix
      metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF)
      proteins, and to analyze their clinicopathological relationship in gastric
      cancer. METHODS: Vascular invasion and remote metastasis were examined in nude
      mice inoculated with SGC-7901 cells, vector control cells or TGIF transfected
      cells via serial sections, and sequentially the expressions of MMP2, MMP9 and
      VEGF proteins in tumor tissues from nude mice were detected by
      immunohistochemical staining. At the same time, TGIF, MMP9 and VEGF proteins were
      examined in 76 patients with gastric carcinoma, and the relationships between the
      expressions of the three proteins and clinicopathological features were analyzed.
      RESULTS: Metastasis was not observed in nude mice inoculated with any cells.
      There were cancerous embolisms in nude mice tumor tissue inoculated with SGC-7901
      cells and vector control cells, but not in TGIF transfected cells. The
      expressions of MMP9 and VEGF proteins were higher in the tumor tissues originated
      from SGC-7901 cells and vector control cells than that from TGIF transfected
      cells. The expression of MMP2 had no distinct difference among the tumor tissues
      originated from the three cells. The positive rate of TGIF protein in gastric
      carcinoma was 46.1% (35/76), obviously lower than that in surgical marginal
      mucosa (78.1%) (P < 0.05). Low expression of TGIF protein correlated
      significantly with the metastasis of lymph node. The positive rates of MMP9 and
      VEGF proteins in gastric carcinoma were 59.2% and 56.6%, respectively, obviously
      higher than that in surgical marginal mucosa (31.3%) (P < 0.05). High expressions
      of both MMP9 and VEGF also correlated significantly with the metastasis of lymph
      node. The expression level of VEGF protein was also associated with the invasion
      of gastric carcinoma (P < 0.05). The expression of TGIF protein reversely
      correlated with that of MMP9 and VEGF proteins (P < 0.05). CONCLUSION: TGIF may
      inhibit the invasion and metastasis of gastric carcinoma via the downregulation
      of MMP9 and VEGF proteins.

PMID- 16562681
TI  - [Primary culture of human omental preadipocytes].
AB  - OBJECTIVE: To establish a primary culture method of human omental preadipocytes.
      METHODS: Using enzyme-digesting method, fibroblast-like cells from the human
      omental adipose tissues were cultured, and then differentiated by conditional
      medium, and identified by oil red O staining. RESULTS: The cultured cells were
      highly homogeneous, and highly proliferative in 4-5th generation. During the
      process of induction by conditional medium, the cells became round-like and
      larger, and more adipose droplets were aggregated. By oil red O staining, we
      confirmed the differentiated cells were mature adipocytes. CONCLUSION: In human
      omental adipose tissues, there are some preadipocytes, which can differentiate
      into mature adipocytes with appropriate stimulus.

PMID- 16562682
TI  - [Orientation of three lysosomal enzymes in the mouse inner ear and hearing loss
      in enzyme gene deficiency].
AB  - OBJECTIVE: To determine the distribution and influence of lysosomal neuraminidase
      (Neul), protective protein/cathepsin A (PPCA) and beta-galactosidase (beta-gal)
      in the inner ear of the mouse, and to observe their auditory alterations in
      enzyme deficiency. METHODS: Six wild type (2 months postnatal) (Neu1+/+, PPCA+/+
      and beta-gal+/+) mice were used, and Neu1, PPCA and beta-gal homozygous (Neu1-/-,
      PPCA-/- and beta-gal-/-) mice at the same age used as control in this experiment.
      The auditory thresholds were examined through the auditory brainstem responses
      (ABR) to click, which tone pips were 8, 16, and 32 kHz. The mice were
      intracardically perfused with 4% paraformaldehyde. The bulla were further fixed
      in 4% paraformaldehyde, processed and sectioned with paraffin embedded method.
      Immunohistochemistry was used to determine the cellular localizations of Neu1, PP
      CA, and beta gal in the inner ear. RESULTS: There was a similar distributive
      pattern of Neu1, PPCA and betagal in the inner ear. Neu1 intense staining was
      observed in the cochlear spiral ganglion cells, spiral limbus, spiral ligament,
      vestibular ganglion cells, cristae, maculae hair cells, and weak staining in
      inner hair cells, outer hair cells, supplying cells of the organ of Corti and
      stria vascularis. The intense staining of PPCA and beta-gal were observed in the
      spiral ganglion and vestibular ganglion cells, and weak staining in the spiral
      limbus, spiral ligament, stria vascularis and organ of Corti. The inner ear
      exhibited no staining when Neul, PPCA and beta-gal were deficient, respectively.
      A positive staining of PPCA and beta-gal was presented in Neu1-/- mice, and as
      well as Neu1 and PPCA in beta-gal-/- mice. However, the staining of Neu1 was not
      presented, and only very weak staining of beta-gal in PPCA-/- mice. The auditory
      thresholds of Neul, PPCA, and beta-gal mice were elevated for 60-69 dB, 40-48 dB,
      and 7-10 dB above those of wildtype littermates, respectively. CONCLUSION: Neu1
      PPCA and beta-gal are distributed in the inner ear of mouse, and the three
      enzymes also form a lysosomal multi-enzyme complex in the inner ear. The
      respective enzyme deficiencies can induce the hearing the loss of different
      levels.

PMID- 16562683
TI  - [Immune tolerance induced by combined heart-thymus transplantation with
      intrathymic inoculation of thymocytes in rats].
AB  - OBJECTIVE: To explore the role of allo heart and thymus transplantation by
      intrathymic inoculation of thymocytes. METHODS: Wistar recipients were given
      intrathymic injection of allo thymocytes (2 x 10(7)) 14 days before the heart
      and/or thymus transplantation. Graft survival, histopathology, levels and mRNA
      expressions of IL-2, IL-4 in serum and cardiac-grafts were investigated. RESULTS:
      Heart transplantation and heart-thymus composite transplantation with the
      treatment of CysA for 7 or 14 days prolonged graft survival. Heart
      transplantation and heart-thymus composite transplantation with intrathymic
      thymocytes injection induced the long-term survival of allo-grafts transiently
      immunosuppressed with CysA; IL-4 maintained at high levels but IL-2 kept at low
      levels in grafts in long-term survivals. CONCLUSION: Intrathymic inoculation of
      allo thymoctyes can induce immune tolerance for both cardiac transplantation and
      heart-thymus combined transplantation in rats. Thymus graft may play a role in
      the induction and maintenance of central tolerance.

PMID- 16562684
TI  - [Effects of different doses of fentanyl on the stress response in patients
      undergoing valve replacement].
AB  - OBJECTIVE: To investigate the effects of different doses of fentanyl on the
      stress response in valve replacement surgery during cardiopulmonary bypass (CPB).
      METHODS: Thirty ASA II-III adult patients scheduled for cardial valve replacement
      were randomly divided into 3 groups: Group A (fentanyl 30 microg/kg), Group B
      (fentanyl 60 microg/kg), and Group C (fentanyl 100 microg/kg). Anesthesia was
      induced with medazalam 0.1 mg/kg, fentanyl 10 microg/kg and vecuronium 0.1 mg/kg;
      And were maintained with fentanyl and propofol infusion. Remained dose of
      fentanyl was used before the CPB. MAP, CVP, HR, P(ET)CO2, SpO2, nasal and rectal
      temperature were monitored continuously. Blood samples were taken before the
      operation (T1), before the CPB (T2), 30 min after the aortic declamping (T3), 2 h
      after the aortic declamping (T4), 24 h (T5) after the operation to determine the
      plasma levels of glucose, adrenocorticotropic hormone (ACTH), angiotensin II (AT
      II) and cortisol. RESULTS: Levels of glucose, ACTH, AT II and cortisol after the
      CPB (T3, T4 and T5) in 3 groups were significantly increased compared with that
      of T1 (P < 0.05 or P < 0.01). After CPB, at the same time point, among the 3
      groups, the levels of the above index of Group A were the most highest, that of
      Group C were the most lowest. Glucose, ACTH, AT II and cortisol levels at T3 and
      T4 were significantly lower in Group B and C than those in Group A ( P < 0.05);
      But there was no significant difference between Group B and C. The duration of
      stay in the ICU and time of endotracheal extubation were significantly longer in
      patients of Group C than Group A and B (P < 0.05). CONCLUSION: Fentanyl (30-100
      microg/kg) can completely suppress the stress response induced by intubation and
      intense surgical stimulus before CPB. Different doses of fentanyl seemed to be
      effective in reducing CPB-induced stress response. But the effect was not
      dependent on dose. So 60 microg/kg fentanyl seemed to be an ideal dose.

PMID- 16562685
TI  - [Effects of aminoguanidine on the lung injury induced by the total hepatic
      ischemia-reperfusion in rats].
AB  - OBJECTIVE: To investigate the effects of aminoguanidine on the lung injury
      induced by the total hepatic ischemia-reperfusion in rats. METHODS: The total
      hepatic ischemia-reperfusion model was built after blocking of the hepatic porta,
      suprahepatic and infrahepatic vena cava. Ninety Sprague-Dawley rats were assigned
      randomly into 3 groups: Sham operation group (Group A, n=30); total hepatic
      ischemia group (Group B, n=30); and aminoguanidine treatment group (Group C,
      n=30). Each group was subdivided randomly into 3 subgroups (n=10) according to
      different time phases: 20 minutes after the total hepatic vascular exclusion
      (T0), 4 hours after the reperfusion (T1), and 48 hours after the survival Group A
      and Group B were intravenously injected with normal saline ( mL/kg) while Group C
      was injected with aminoguanidine (20 mg/kg) dissolved in normal saline (1 mL/kg)
      10 minutes before the open of the abdomin. The levels of portal blood nitric
      oxide ( O) endotoxin ( ET), tumor necrosis factor-alpha (TNF-alpha at T0 and T1
      were detected; 48 hours survival rates and the lung wet/dry weight ratio were
      counted; and the histological changes of the lung tissues were observed. RESULTS:
      Compared with Group A, the levels of portal vein NO, ET, and TNF-alpha T0 and T1
      in Group B and Group C were significantly higher (P < 0.05 or P < 0.01). But
      those indexes of Group C were lower than those of Group B (P < 0.05). The 48-hour
      survival rate in Group C was higher than that in Group B (P < 0.05). The lung
      wet/dry weight ratio in Group C was lower than in Group B (P < 0.05) and the
      histological change of Group C was slighter than that in Group B. CONCLUSION:
      Aminoguanidine has the protective effects on the lungs against the total hepatic
      ischemia-reperfusion induced injury.

PMID- 16562686
TI  - [Sevoflurane-N2O inhalation anaesthesia with laryngeal mask airway and propofol
      ketamine intravenous anaesthesia in strabismus surgery].
AB  - OBJECTIVE: To investigate the advantages and disadvantages of sevoflurane-N2O
      inhalation anesthesia with laryngeal mask airway (LMA) and propofolketamine total
      intravenous anaesthesia in children undertaking strabismus surgery. METHODS:
      Eighty children undertaking strabismus surgery were randomly divided into
      sevoflurane-N2O inhalation anaesthesia group with LMA (volatile group, n=40) and
      propofol-ketamine total intravenous anesthesia group (TIVA group, n=40). LMA was
      used to secure respiratory airway in the volatile group, but LMA or endotracheal
      intubation was not used in the TIVA group. All children breathed spontaneously
      during operative period. The anesthesia was maintained with 2%-3% sevoflurane-50%
      N2O-50% O2 in the volatile group, and continuous intravenous infusion with
      propofol 5-10 mg/(kg x h) plus ketamine 1-2 mg/(kg x h) in the TIVA group. The
      incidence of SpO2 less than 95% and the movement of the limbs and head induced by
      operative stimulation, oculocardiac reflex (OCR) and postoperative vomiting (POV)
      were recorded in all children. RESULTS: The incidence of limbs and head movement,
      the incidence of SpO2 less than 95% and OCR were significantly lower in the
      volatile group than those in the TIVA group (P < 0.01); but the incidence of POV
      was significantly higher in the volatile group than that in the TIVA group (P <
      0.01). CONCLUSION: Sevoflurane-N2O-O2 anesthesia with LMA can secure respiratory
      airway of patients, avoid hypoxemia, and have good anesthetic quality and low OCR
      incidence. It is a new anesthesia method with more advantages in children
      undertaking strabismus surgery, but the prevention and treatment of POV must be
      noticed.

PMID- 16562687
TI  - [Auditory evoked potentials index for monitoring the depth of desflurane
      anesthesia in the elderly].
AB  - OBJECTIVE: To observe the changes of auditory evoked potentials (AEP) index, mean
      arterial blood pressure (MAP) and heart rate (HR) undergoing desflurane
      anesthesia in the elderly and to evaluate the use of AEP index for monitoring the
      depth of desflurane anesthesia in the elderly. METHODS: Forty patients classified
      as ASA physical status I-III undergoing general anesthesia were divided into 2
      groups with 20 patients in each group: Group elderly (> or =65 years) and Group
      youth (18-55 years). Anesthesia was induced with propofol and vecuronium. After
      the endotracheal intubation, the lungs were ventilated with desflurane in oxygen.
      End-tidal concentration of desflurane was maintained at 0.6 MAC, 1.0 MAC and 1.3
      MAC for 20 min, respectively. The changes of MAP, HR and AEP index were recorded
      simultaneously. RESULTS: During the anesthesia of desflurane, MAP decreased
      significantly compared with those at preanesthesia in both groups. And HR
      decreased significantly compared with those at preanesthesia only in Group
      elderly (P < 0.05). The changes of MAP and HR had no statistical difference with
      increasing end-tidal desflurane concentration from 0.6 MAC to 1.3 MAC in both
      groups (P > 0.05). During the anesthesia of desflurane, AEP index decreased
      significantly compared with those at preanesthesia in both groups (P < 0.05). In
      the periods of increasing concentration of desflurane, AEP index decreased
      gradually. In Group elderly, AEP index decreased significantly 1.0 MAC and 1.3
      MAC of desflurane compared with those of 0.6 MAC (P < 0.05). In Group youth, the
      changes of AEP index had no statistical difference with increasing end-tidal
      desflurane concentration from 0. 6 MAC to 1.3 MAC (P > 0.05). At the same
      concentration of desflurane, AEP index in the Group elderly were less than those
      in Group youth (P < 0.05). AEP index correlated with the end-tidal desflurane
      concentration significantly. The coefficient of product-moment correlation (r)
      were -0.983 and -0.980, respectively in Group elderly and Group youth (P < 0.05).
      CONCLUSION: AEP index correlates well with the end-tidal desflurane concentration
      which is valuable for monitoring the depth of desflurane anesthesia in the
      elderly. AEP index can show the different depth of anesthesia at the same end
      tidal desflurane concentration between the elderly and youth.

PMID- 16562688
TI  - [Preliminary study on treating patellar instability guided by arthroscopy].
AB  - OBJECTIVE: To explore the operation method in treating patellar instability
      guided by arthroscopy and to evaluate its therapeutic effects. METHODS: Thirty
      two patients (34 knees) with patellar instability including 2 patellar tilt (2
      knees), 26 (27 knees) patellar subluxation, and 4 (5 knees) patellar dislocation,
      diagnosed by clinical and arthroscopical standard, were treated with anterior
      transfer of the gracilis or medial transfer of the tibial tuberosity based on the
      lateral retinacular release and medial tightening. RESULTS: Twenty-eight patients
      were followed up for 5-87 (mean 36.6) months. The excellence rates was 92.8%.
      CONCLUSION: The patellofemoral alignment can be seen directly and dynamically
      under the arthroscopy. The combinational treatment including anterior transfer of
      the gracilis in repairing patellar instability can avoid the recurrence
      effectively and get satisfactory results.

PMID- 16562689
TI  - [Clinic and pathology of the knee menisci injury with sclerosis
      denaturalization].
AB  - OBJECTIVE: To summarize the characteristics of clinic and pathology of the knee
      menisci injury with sclerosis denaturalization and to discuss the mechanism of
      the sclerosis and its clinic significance. METHODS: We retrospectively analyzed
      the diagnosis and treatment and healing of the knee menisci with the sclerosis
      denatured injury from 1989 to 2003. The changes of the partial meniscus with
      sclerosis denaturalization were observed in tissue section. RESULTS: Menisci with
      sclerosis denaturalization occupied 24.1%, and 77.6% of them subordinated to
      simple sclerosis denaturalization without tear. Their characteristics were that
      the manifestations were not except typical knee pain, tenderness at joint
      line,integrity shape with dull or less lubricity and tiny grand on the super face
      of menisci under the arthroscopy,and trembles could be touched by a probe.
      Pathology showed the formation of local sclerosis with the histological changes
      of fibro-hyperplasia, hyaline degeneration and mucous degeneration in the
      menisci. No operation obtained curative effects. Symptoms can be eliminated by
      the excision of the menisci with sclerosis denaturalization. CONCLUSION: The
      clinic of simple meniscus injury with sclerosis denaturalization are non-typical
      and arthroscopic check-up is valuable for the diagnosis. The menisci can be
      removed from the patients suffered from heavy symptoms for a long time.

PMID- 16562690
TI  - [Diagnosis and treatment of postoperative intervertebral infectio].
AB  - OBJECTIVE: To retrospectively explore the diagnosis and treatment of
      postoperative lumbar intervertebral disc infection. METHODS: Twelve patients who
      suffered from postoperative lumbar intervertebral disc infection between April
      1995 and September 2004 were confirmed doubtlessly by the diagnosis. They were
      treated with early immobilization combined with early and sufficient antibiotics
      and adequate corticosteroid. Patients with severe symptoms were managed by
      percutaneous puncture and washing discectomy such as rising temperature and
      perivertebral muscle spasm besides nostalgia, and early debridement of all
      necrotic tissue was done. RESULTS: Six were healed by non-operation and operation
      in the other 6. All had gotten locomotion with corset after the operation for 6-8
      weeks and were followed-up from 6 months to 3 years. They have achieved excellent
      outcomes. CONCLUSION: When a postoperative disc space infection occurs, early
      diagnosis and treatment should be undertaken to achieve excellent outcomes.

PMID- 16562691
TI  - [Preliminary clinical application of percutaneous vertebroplasty].
AB  - OBJECTIVE: To investigate the clinical application of percutaneous vertebroplasty
      (PVP). METHODS: PVP was performed in 21 cases of 37 vertebral lesions,including
      14 osteoporotic compression fractures, 6 metastases, 1 hemangioma,and 17 lesions
      in thoracic vertebra and 20 in lumbar. The procedures of PVP were as follows: The
      needle was inserted via percutaneous transpedicular approach or percutaneous
      posterolateral vertebral approach; the needle tip was placed at the junction of
      the anterior located the one third of the vertebral body; intraosseous venography
      was performed; and last bone cement was injected at 2-10 mL. The technical
      success rate, clinical efficacy and complications were observed after the
      procedure. Results The procedure was successful in 18 cases with 31 lesions,and
      the success rate according to the number of cases and vertebral lesions was 85.7%
      (18/21) and 83.8% (31/37), respectively. After the procedure, the numbers of
      complete remission, partial remission, mild remission and no remission were 10,
      5, 2 and 1, respectively; and the total effective rate was 94.4% (17/18).
      Progressive compression did not occur. Three patients had transient neuropathy
      and recovered after physiotherapy. Other complications were insignificant; no
      severe complications occurred. Conclusion PVP is an effective and micro-traumatic
      treatment for patients with benign and malignant lesions in vertebral bodies.

PMID- 16562692
TI  - [Application of sequential noninvasive following invasive mechanical ventilation
      in COPD patients with severe respiratory failure by investigating the appearance
      of pulmonary-infection-control-window].
AB  - OBJECTIVE: To evaluate the application of sequential noninvasive following
      invasive mechanical ventilation in chronic obstructive pulmonary disease (COPD)
      patients with severe respiratory failure by investigating the appearance of
      pulmonary-infection-control-window. METHODS: From November 2001 to October 2004,
      76 case of COPD patients with severe respiratory failure due to pulmonary
      infection were intubated and recruited in the study. When the pulmonary infection
      was significantly controlled (the time of pulmonary infection control was called
      PIC window) by the antibiotic and comprehensive therapy, all cases were
      randomized into noninvasive veatiation group (NIV) and control group. The early
      extubation was conducted and followed by noninvasive mechanical ventilation via
      facial mask with bilevel positive airway pressure mode immediately in the NIV
      group. Conventional invasive synchronized intermittent mandatory ventilation
      (SIMV) plus pressure support ventilation (PSV) was used as the weaning technique
      in the control group. RESULTS: Thirty eight cases among 76 patients were in the
      NIV group, and the rest in the control group. The NIV group and the control group
      had similar age, sex, APACHE scores, RR, HR, MAP, PaO2 and PaCO2 at the time of
      commencement and PIC window (P > 0.05). The time of PIC window was (7.5 +/- 1.9)
      d in the NIV group, and (8.0 +/- 2.5) d in the control group (P > 0.05). In the
      NIV group, the durations of invasive mechanical ventilation (MV) and total MV
      were (7.5 +/- 1.9) d and (12.5 +/- 4.0) d respectively, while the durations were
      (23.5 +/- 9.5) d in the control group (P < 0.05). The durations of RICU stay and
      hospital stay were shorter than that in the control group. The incidence of
      ventilation associated pneumonia (VAP) was 18.4% (7/38) in the NIV group, 39.5%
      (15/38) in the control group respectively (P < 0.05). The incidence of
      reintubation was 13.2% (5/38) in the NIV group, 34.2% (13/38) in the control
      group respectively (P < 0.05). Hospital mortality was 7.9% (3/38) in the NIV
      group, and 28.9% (11/38) in the control group (P < 0.05). CONCLUSION: In those
      COPD patients requiring intubation and mechanical ventilantion who have severe
      respiratory failure due to pulmonary infection, sequential noninvasive following
      invasive mechanical ventilation at the appearance of PIC window can significantly
      reduce the MV duration, the length of RICU stay and hospital stay, and decrease
      the occurrence of VAP, reintubation and hospital mortality as well. So it is an
      efficient strategy to be generalized.

PMID- 16562693
TI  - [Relevant factors of lymphatic metastasis in rectal carcinoma].
AB  - OBJECTIVE: To investigate the rules of lymphatic metastasis of rectal carcinoma,
      and to help clinical diagnosis and treatment. METHODS: A retrospective analysis
      was performed in the 979 patients with rectal carcinoma who underwent surgical
      resection from 1995 to 2004. The associations between lymphatic metastasis and
      clinicopathologic variables were evaluated by Chi-squared test and logistic
      regression. RESULTS: The rate of lymph node metstasis was 71.4% for patients
      younger than 30 years old, 40.7% in the patients with tumor diameters over 6
      centimeters, 82.5% in the patients with extraneous tumor invasion, 71.6% for
      patients of poor-differentiated adenocarcinoma, 70.4% for patients with mucoid
      adenocarcinoma, 100% for patients with signet-ring cell carcinoma and 46.4% for
      patients with more than half intestinal circumference invasion. Logistic
      regression analysis showed that the degree of lymphatic metastasis was related to
      the differentiating degrees, depths of tumor invasion and intestinal
      circumference invasion, and the differentiating degree was the major factor.
      CONCLUSION: The lymphatic metastasis of rectal carcinoma is related to age, tumor
      size, intestinal circumference invasion, depth of tumor invasion and the
      differentiating degree of the tumor; the differentiating degree is the major
      factor.

PMID- 16562694
TI  - [Clinical analysis of histocytic necrotizing lymphadenitis].
AB  - OBJECTIVE: To understand the clinical features and histopathology of histocytic
      necrotizing lymphadenitis (HNL) so as to better recognize the disease. METHODS:
      The clinical features, histopathology, and diagnosis of 10 patients admitted to
      our hospital were retrospectively analyzed. RESULTS: The clinical features of
      these 10 cases included: young females were the majority; lymphadenopathy and
      fever were the most common clinical manifestations; some cases were accompanied
      by connective tissue diseases. Histopathologic examination showed distinctive
      necrosis and around the necrotic foci, variable proliferations of histocytes but
      generally without infiltration of neutrophils. CONCLUSION: HNL has some typical
      histopathological alterations and relatively fine prognosis,but it tends to be
      misdiagnosed as lymphoma or lymphoid tuberculosis and may be accompanied by other
      diseases.

PMID- 16562695
TI  - [Emergence of AmpC enzyme and antibiotics resistance in gram-negative bacilli].
AB  - OBJECTIVE: To investigate the relationship between emergence of AmpC enzyme and
      drug resistance in the gram-negative bacilli in Xiangya Hospital and to provide
      information for the treatment of antibiotics. METHODS: The bacteria were
      identified; the susceptibility was determined by Microscan microbiological
      identification system; and the AmpC enzyme was detected by disc diffusion method.
      RESULTS: Of the 204 gram-negative strains, the positive rate of AmpC enzyme was
      19.61%; AmpC-positive strains resisted to ceftriaxone, piperacillin, ceftazidime,
      cefotaxime, cefoperazone, aztreonam, piperacillin/tazobactam, cefuroxime,
      ceftazidime/clavulanic, and cefotaxime/clavulanic. But AmpC-negative strains were
      susceptible to those antibiotics. There were significant differences, between the
      two groups (All P < 0.05). Both groups were susceptible to cefepime, imipenem,
      meropenem, cefoperazone/sulbactam, levofloxacin, and amikacin. CONCLUSION: The
      detection of AmpC enzyme is helpful to the screen of drug resistant strains. Most
      bacilli with AmpC enzyme show the resistance to third-generation cephosporins,
      aztreonam, and the beta-lactamase inhibitors, but susceptible to imipenem,
      cefepime, meropenem, cefoperazone/sulbactam, levofloxacin, and amikacin, which
      provides the information for the antibiotic therapy.

PMID- 16562696
TI  - [Ability of catechin to eliminate O2-* and *OH].
AB  - OBJECTIVE: To investigate the eliminating ability of catechin to eliminate O2-*
      and *OH. METHODS: The ability of catechin to clear away O2-* and *OH was
      respectively measured by faintness chemiluminescence and spin trapping assay.
      RESULTS: IC50 that catechin eliminated O2-* and *OH was 6.16, 0.59 g/mL
      respectively, and the eliminating ability of catechin was much stronger than that
      of the extract from liquorice, rosemary, grape pip, giant knotweed and ginkgo
      leaf. CONCLUSION: Compared with several important natural plants of antioxidants,
      the eliminating ability of cathechin is the best.

PMID- 16562697
TI  - [Progression of lipopolysaccharide signal pathway].
AB  - Lipopolysaccharide (LPS) is the major constituents of the outer membrane of Gram
      negative bacteria. LPS recognition and signal transmission are key events in the
      host defense reaction towards Gram-negative bacteria and are associated with many
      disorders. Multiple signaling pathways are involved in the response to LPS. With
      the help of LPS-binding protein and CD14, TLR4 binds with LPS, then recruits
      myeloid differentiation factor 88 and IL-1 receptor-associated kinase, and
      further phosphorylates and activates TNF receptor associated factor 6 (TRAF6).
      The activated TRAF6 leads to the activation of transcription factor NF-kappaB and
      MAP kinase's pathways that involves in LPS-induced cellular responses and the
      production of proinflammatory cytokines such as TNF-alpha, IL-6 and IL8.

PMID- 16562698
TI  - [A case of repaired peritoneal catheter].

PMID- 16562699
TI  - The Global Plan to Stop TB, 2006-2015.

PMID- 16562700
TI  - The Global Plan to Stop TB, 2006-2015. actions for life: towards a world free of
      tuberculosis.

PMID- 16562701
TI  - Environmental determinants associated with the development of asthma in
      childhood.
AB  - Asthma is a common chronic respiratory disease, and many epidemiological studies
      have documented an increasing trend over the past few decades. Comparative
      studies have shown that asthma is more prevalent in Westernised societies than in
      rural or developing regions. Environmental factors are likely to be important in
      explaining such disparities and increasing trends. Although allergen exposure and
      atopic sensitisation have been thought to be important in the pathogenesis of
      asthma, recent cross-sectional and longitudinal studies suggest that allergic
      sensitisation is likely a marker rather than a causative factor for asthma. There
      is accumulating evidence confirming the role of early exposure to infections in
      altering the regulation of cytokine production and reduction of subsequent
      development of atopic disorders. The consistent finding of a lower prevalence of
      asthma in subjects brought up in a farming environment and the inverse
      relationship between microbial exposure and asthma symptoms further support the
      importance of early environmental exposure affecting the risk of subsequent
      development of asthma. Confirmation of the pathogenetic role of these
      environmental determinants may allow us to develop primary preventive strategies
      against the development of asthma and related atopic diseases.

PMID- 16562702
TI  - How to diagnose asthma and determine the degree of severity of the disease.
AB  - Asthma care begins with establishing the diagnosis and determining the severity
      of the disease. The key elements are the history of the disease and the
      measurements of peak expiratory flow (PEF). The characteristic of asthma is
      variability. A history of chest symptoms that are variable is typical of asthma.
      Demonstrating a variation of PEF > or = 20% establishes a definite diagnosis of
      asthma. This variability is demonstrated either, in patients with normal PEF when
      they are well, by measuring a decrease in PEF during a period when the patient
      has symptoms of asthma or, in patients with PEF < normal, an improvement after
      inhalation of salbutamol or after a period of treatment. Classifying the severity
      of asthma is also based on history and lung function measurement. Patients with
      PEF <60% or continuous symptoms are classified as severe persistent. Those with
      PEF 60-79% or daily symptoms (not continuous) are classified as moderate
      persistent. Those with symptoms more than once per week but less than daily and
      PEF > or = 80% are classified as mild persistent. Those with symptoms less than
      once per week and PEF > or = 80% are classified as intermittent. Establishing the
      diagnosis and assessing the severity are crucial to high quality care.

PMID- 16562703
TI  - The bleach microscopy method and case detection for tuberculosis control.
AB  - The World Health Organization (WHO) and the International Union Against
      Tuberculosis and Lung Disease (The Union) recommend direct sputum smear
      microscopy for tuberculosis (TB) case finding in resource-poor settings. This
      method is associated with poor sensitivity. Digestion of sputum with bleach prior
      to smear preparation has been reported to increase sensitivity. Some workers,
      having reviewed the relevant literature, have called for the WHO and The Union to
      advocate for a shift to this methodology for TB case finding. This article
      highlights deficiencies in the scope and detail of available evidence, and
      cautions against the premature, and possibly counter-productive, adoption of so
      called 'bleach microscopy'. Further well-guided research is required to answer
      policy-relevant gaps in our knowledge about this promising technology.

PMID- 16562704
TI  - The burden of childhood tuberculosis and the accuracy of community-based
      surveillance data.
AB  - BACKGROUND: Inadequate surveillance and diagnostic difficulties compromise the
      quality of epidemiological data on childhood tuberculosis (TB). OBJECTIVE: To
      document the incidence of childhood TB and to evaluate the accuracy of community
      based surveillance data in a high-burden setting. METHODS: This prospective
      observational study was conducted from February 2003 to October 2004 at five
      primary health care clinics in Cape Town, South Africa. Comprehensive
      surveillance was done to ensure that all children <13 years of age treated for TB
      were included. RESULTS: During the study period, 443 children (<13 years of age)
      received anti-tuberculosis treatment, of whom 389 (87.8%) were recorded in the TB
      treatment register. The TB incidence calculated from the TB treatment register
      was 441/100,000/year amongst children and 845/100,000/year amongst adults. Fifty
      four children treated for TB were not recorded in the TB treatment register,
      including 21/28 (75%) children with severe disease. DISCUSSION: Children <13
      years of age contributed 13.7% of the total TB burden, but experienced more than
      half (52.2%) the TB incidence recorded in adults. Community-based surveillance
      data excluded the majority of children with severe disease. The accuracy of
      surveillance data is an important consideration when describing the epidemiology
      of childhood TB or measuring the success of public health interventions.

PMID- 16562705
TI  - Involvement of private practitioners in tuberculosis control in Ballabgarh,
      Northern India.
AB  - SETTING: The Revised National Tuberculosis Control Programme (RNTCP) in India
      covered 70% of the population in 2003. However, the private sector, where a large
      proportion of tuberculosis (TB) patients are seen, does not have sufficient
      involvement in the programme. OBJECTIVE: To test the feasibility of involving
      private practitioners (PPs) in the RNTCP for identification and management of TB
      cases. DESIGN: PPs in Ballabgarh Block, Haryana, were identified and invited for
      training in RNTCP guidelines. They referred TB suspects for confirmation of
      diagnosis to a nearby public facility. Patients could subsequently choose to
      return to their referring doctor or to the government facility. Patients and
      doctors were interviewed at the end of the project to assess their perceptions.
      RESULTS: Of 146 PPs, 72% were trained in RNTCP guidelines and 14 agreed to
      provide directly observed treatment (DOT). During the study period (May 2001
      December 2003) 113 patients initiated treatment, leading to an incremental gain
      of 11.5% in case finding. The cure rate among the 113 sputum positive patients
      was 73%, and the default rate was 11.5%. CONCLUSION: Involvement of private
      practitioners in TB control is possible and results in benefits for all
      stakeholders.

PMID- 16562706
TI  - Factors affecting patient adherence to DOTS in urban Kathmandu, Nepal.
AB  - SETTING: The urban area of Kathmandu has a population of one million, with an
      annual risk of tuberculosis (TB) infection of 4%. It is estimated that up to 200
      people default from treatment in Kathmandu annually, giving a defaulter rate of
      10%. OBJECTIVES: To identify the socio-demographic factors, availability and
      accessibility of DOTS services and behavioural factors affecting patient
      adherence to DOTS. METHODS: Structured questionnaire of a random sample of 234
      new smear-positive TB patients enrolled on treatment. Analysis of socio
      demographic, psychosocial factors and availability and accessibility of DOTS
      services. Sub-analysis of non-adherent (missed >7 consecutive treatment days) vs.
      adherent patients. RESULTS: Reasons given by non-adherent patients included 61%
      who claimed insufficient knowledge about the need to take daily treatment,
      especially after they felt better. Directly observed treatment, younger age,
      knowledge of TB and availability of daily health education were associated with
      increased adherence. Daily health education and knowledge of TB and its treatment
      were independently associated with adherence on multivariate analysis (OR 6.27,
      95%CI 2.88-13.64, P < 0.001). CONCLUSION: Daily health education delivered at
      DOTS centres is strongly associated with improved adherence. Adherence throughout
      treatment needs emphasis.

PMID- 16562707
TI  - Evaluation of sputum smear microscopy in the National Tuberculosis Control
      Programme in the north of Vietnam.
AB  - OBJECTIVE: To assess the yield of sputum smear microscopy and sex differences in
      the National Tuberculosis Control Programme in the north of Vietnam. METHODS:
      Review of registers of 30 randomly selected laboratories (26 district, 4
      provincial level). RESULTS: The average daily workload per technician was 4.4
      examinations in district and 5.3 examinations in provincial laboratories. To find
      one smear-positive case, 9.7 suspects were examined and 29.3 smears done. The
      smear-positive rate (mean 10.3%) was higher among men (11.6%) than among women
      (8.4%, P < 0.001). There were more men than women among tuberculosis (TB)
      suspects (male:female ratio 1.36, 95%CI 1.19-1.54), but even more so among smear
      positive patients (1.89, 95%CI 1.64-2.14), irrespective of specimen quality and
      number of smears examined. Three smears were examined for 18,055 suspects
      (61.7%). The incremental gain was 33.5% and 4.9% for the second and third smear
      examination, respectively; 186 (95%CI 160-221) smears needed to be examined to
      find one additional case of TB with a third serial examination. CONCLUSION: The
      diagnostic process seemed generally efficient. The male:female ratios suggest
      higher TB incidence in men rather than lower access to TB facilities for women.
      The third smear examination could be omitted.

PMID- 16562708
TI  - Tuberculosis drug resistance and treatment outcomes under DOTS settings in large
      cities in the Philippines.
AB  - SETTING: Two large cities in the Philippines. OBJECTIVES: To describe the
      problems of drug-resistant tuberculosis (TB) in an urban setting, with special
      emphasis on their potential impact on the treatment services provided by the
      National TB Control Programme. DESIGN: Cross-sectional survey and cohort analysis
      of treatment outcomes. METHODS: All patients with positive sputum smear
      examination results in Cebu and Mandaue cities during the survey period were
      included. The survey procedures of the World Health Organization and the
      International Union Against Tuberculosis and Lung Disease were strictly applied.
      Treatment outcome data were also collected. RESULTS: Of 306 cases enrolled, 255
      were new cases, 28 were previously treated and for 23 treatment history was
      unknown. Of the new cases, 72.2% were pan-susceptible to all four first-line anti
      tuberculosis drugs. Resistance in new cases was 16.9% to isoniazid (INH), 4.7% to
      rifampicin (RMP), 3.1% to ethambutol, 18.0% to streptomycin, and 3.9% to at least
      both INH and RMP (multidrug-resistant [MDR]). Over 90% of the new cases, either
      pan-susceptible or mono-resistant, were successfully treated with the standard
      regimen, but four of nine MDR new cases could not be cured. CONCLUSION: The drug
      resistance level was high in this population, but treatment outcome using the
      standard treatment regimen was not seriously affected unless the patients were
      MDR.

PMID- 16562709
TI  - Representative drug susceptibility patterns for guiding design of retreatment
      regimens for MDR-TB.
AB  - BACKGROUND: There is no gold standard on how national tuberculosis programs
      should design retreatment regimens. Often drug susceptibility testing (DST) is
      not available for all patients, and representative DST patterns in patient
      populations are used to guide therapy. OBJECTIVES: To examine DST patterns in
      different patient populations based on previous treatment and to estimate the
      number of effective anti-tuberculosis agents in several retreatment regimens.
      METHODS: We reviewed DST results from patients treated with individualized
      regimens in Peru between January 1998 and July 2004. We stratified patients into
      four groups based on previous treatment exposure from Group 1 who had failed only
      one regimen to Group 4 who had failed three regimens. We compared resistance
      frequencies across the four groups. In Groups 1 and 3, the number of likely
      effective agents under six possible retreatment regimen scenarios was estimated.
      RESULTS: Resistance to second-line drugs was significantly higher in groups with
      more previous courses of treatment. A few retreatment regimens could be
      identified that would allow at least 80% of patients to receive at least four
      likely effective drugs. CONCLUSION: Because it is associated with resistance
      frequencies, previous treatment exposure can serve to guide the design of non
      individualized MDR-TB regimens.

PMID- 16562710
TI  - A 13-year molecular epidemiological analysis of tuberculosis in San Francisco.
AB  - BACKGROUND: We examined the molecular epidemiology of tuberculosis (TB) in San
      Francisco during a 13-year period encompassing the peak of TB resurgence and
      subsequent decline to historic low levels. OBJECTIVE: To compare rates of TB
      caused either by rapid progression of recent Mycobacterium tuberculosis infection
      or by reactivation of latent infection. METHODS: All TB cases reported from 1991
      to 2003 were included. Genotyping was performed to identify clustered cases.
      RESULTS: The annual TB case rate decreased significantly from 50.8 to 28.8
      cases/100000 persons from 1992 to 1999 (P < 0.0001). After 1999, no significant
      decrease was observed for the population as a whole or in any subgroup examined.
      Similarly, the rate of clustered cases decreased significantly from 1992 to 1999
      (11.4 to 3.1 cases/100000, P < 0.0001). Although the rate of non-clustered cases
      also declined significantly (25.6 to 17.6 cases/100,000, P < 0.0001), there was a
      disproportionate reduction in clustered cases (94.7% vs. 50.8%, P < 0.0001).
      Neither clustered nor non-clustered cases decreased significantly after 1999.
      CONCLUSIONS: TB case rates reached a plateau despite ongoing application of
      control measures implemented in 1993. These data suggest that intensification of
      measures designed to identify and treat persons with latent TB infection will be
      necessary to further reduce TB incidence.

PMID- 16562711
TI  - Delay in the treatment of pulmonary TB in a changing demographic scenario.
AB  - OBJECTIVE: To quantify patient and health care delays in the treatment of
      pulmonary tuberculosis (PTB) in Emilia-Romagna region, Italy, and to study the
      association between migration status and delay. DESIGN: All patients with
      symptomatic PTB, aged >15 years, who were notified in Emilia-Romagna during 2003
      and were alive at time of data collection, were included. An individual form was
      completed for each notified patient by the local health authority officer in
      charge of surveillance data. RESULTS: Median patient delay, health care delay and
      total delay were 7, 36 and 65 days, respectively. Recent migrants (stay in Italy
      < or = 3 years) had the longest patient delay (16 days), while Italian patients
      had the longest health care delay (60 days). Migration status was independently
      associated with both patient and health care delay, although the direction of
      association changed according to which delay was considered. CONCLUSION: Public
      health interventions aiming to reduce delay in treatment of PTB should improve
      the access of recent migrants to health care and increase suspicion of TB among
      Italian patients. Studies on delays in treatment of TB should investigate patient
      delay and health care delay as distinct outcomes.

PMID- 16562712
TI  - Comparison of mantoux skin test with three generations of a whole blood IFN-gamma
      assay for tuberculosis infection.
AB  - SETTING: A rural town in South Africa. OBJECTIVE: To compare the performance of
      Quanti-FERON assays with the tuberculin skin test (TST) for identifying latent
      tuberculosis infection (LTBI) in a high TB burden community. DESIGN: In a cross
      sectional study in healthy adults, we applied the TST and took blood for the
      three generations of QuantiFERON assays. RESULTS: Of 358 participants whose
      results were analysed, 291 (81%) had a TST result of > or = 10 mm induration, and
      187 (52%) > or = 15 mm. QuantiFERON-TB was positive in 215 (60%), QuantiFERON-TB
      Gold in 137 (38%), and QuantiFERON-TB Gold (In-Tube method) in 201 (56%). There
      was poor agreement between TST and QuantiFERON tests, and between the different
      generations of QuantiFERON tests (kappa = 0.12-0.50). Of the subset with TST
      indurations > or = 15 mm, 30-56% had negative QuantiFERON tests. However,
      positive Quanti-FERON tests were associated with males, who have a higher
      incidence of TB in this area. CONCLUSION: We showed poor agreement between TST
      and the different QuantiFERON tests in diagnosing LTBI. The surprising
      discordance between the Quanti-FERON TB Gold and QuantiFERON TB Gold (In-Tube
      method) tests needs to be investigated further.

PMID- 16562713
TI  - Sterilising action of pyrazinamide in models of dormant and rifampicin-tolerant
      Mycobacterium tuberculosis.
AB  - SETTING: Pyrazinamide (PZA) is an effective sterilising drug in tuberculosis, but
      its mode of action is controversial. OBJECTIVE: To test the bactericidal activity
      of 1.56-100 microg/ml PZA in Hu/Coates models of dormant and rifampicin (RMP)
      tolerant Mycobacterium tuberculosis. METHODS: In model 1, bactericidal activity
      was tested in pH 5.5 medium against 4-day, 30-day or 100-day static, hypoxic
      cultures. In models 2 and 3, 100 microg/ml RMP was added to a 100-day culture and
      PZA was added either during incubation with RMP in model 3, or after resuspension
      in RMP-free medium in model 2. RESULTS: Model 1: cfu counts on the 100-day and 30
      day cultures fell by a maximum of about 1.6 log cfu/ml with increasing culture
      age, PZA concentration and incubation period, while counts on the 4-day culture
      showed little change. Model 2: cfu counts at the end of 7 days of recovery showed
      little bactericidal activity. Model 3: viable bacilli were almost completely
      eliminated. Bactericidal activity in these models increased with decreasing
      metabolic bactericidal activity, as measured by the uptake of [3H] uridine into
      bacterial RNA. CONCLUSION: PZA differs from other anti-tuberculosis drugs in
      showing greater bactericidal activity the slower the bacillary metabolic
      activity, hence its great value as a sterilising drug, likely to remain as an
      effective companion drug with newer sterilising drugs.

PMID- 16562714
TI  - Survey on tuberculosis teaching in Brazilian nursing schools, 2004.
AB  - OBJECTIVE: To characterise tuberculosis (TB) teaching in Brazilian nursing
      schools by state and region and its theoretical and practical contents.
      METHODOLOGY: In an educational research survey in 2004, 347 nursing schools were
      identified. Questionnaires were posted to faculties providing training in TB.
      Data were compiled in a database with a view to descriptive result analysis.
      Replies to the questionnaire were received by 32% of the nursing schools
      contacted. RESULTS: Undergraduate TB teaching is heterogeneous. For training in
      theory, the principle teaching method is through classes in 102 (91.9%) nursing
      schools. Practical TB teaching is carried out at the primary care level (89.2%).
      Teachers update their knowledge through events and internet; little reference is
      made to manuals. The time devoted to practical TB teaching ranges from 10 to 20
      hours, although this is not always included in student training. CONCLUSION:
      Teaching in TB should go beyond the traditional model that focuses only on
      biological aspects. It should introduce tools that lead to permanent behavioural
      change, such as a more human approach and social and psychological aspects, such
      as living conditions, habits and customs. It should involve new partners, such as
      families, communities and other health professionals, and identify obstacles
      within the university.

PMID- 16562715
TI  - Medical students and tobacco in 2004: a survey in Sousse, Tunisia.
AB  - OBJECTIVE: To assess the behaviour, knowledge and attitudes towards smoking among
      medical students in Sousse, Tunisia. DESIGN: A cross-sectional survey in
      classroom settings using a self-administered questionnaire was conducted at the
      School of Medicine during September 2004. RESULTS: The numbers of students who
      entered the first and the fifth years of medical training at the University of
      Sousse in 2004 and completed the questionnaire were respectively 120 and 110. The
      population age ranged from 18 to 21 years (mean 19 +/- 0.62 years) in first year
      students and from 22 to 30 years (mean 23 +/- 1.38 years) in fifth year students.
      The prevalence of daily smoking (both sexes combined) was 4.5% among first year
      students and 16.7% among final year students. The prevalence of daily smoking
      according to sex was 29.6% among boys and 0.7% among girls. Over 90% of students
      thought smoking was harmful to health, but there was considerable underestimation
      of its causal role in a number of diseases, notably coronary heart disease,
      bladder cancer and peripheral vascular disease. There were important defects in
      both knowledge and motivation regarding counselling patients to stop smoking.
      CONCLUSIONS: The results of this study may provide baseline data to develop an
      anti-smoking programme in the university.

PMID- 16562716
TI  - Dietary fat and meat intake and idiopathic pulmonary fibrosis: a case-control
      study in Japan.
AB  - SETTING: There is sparse epidemiologic information regarding the role of dietary
      factors in the development of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To
      examine the relationship between specific types of fatty acids and selected foods
      high in fat and IPF in Japan. DESIGN: Included were 104 cases aged > or = 40
      years who had been diagnosed in the last 2 years in accordance with the most
      recent criteria. Controls aged > or = 40 years consisted of 56 hospitalised
      patients diagnosed as having acute bacterial pneumonia and four out-patients with
      common cold. RESULTS: Intake of saturated fatty acids, mono-unsaturated fatty
      acids, n-6 polyunsaturated fatty acids and meat was independently associated with
      an increased risk of IPF. Specifically, the multivariate OR for comparison of the
      highest with the lowest quartile of intake of saturated fatty acids was 6.26
      (95%CI 1.79-24.96, P for trend = 0.01) and for meat it was 7.19 (95%CI 2.15
      27.07, P for trend = 0.02). Intake of cholesterol, n-3 polyunsaturated fatty
      acids, fish, eggs and dairy products was not related to the risk. CONCLUSION:
      These findings suggest that consumption of saturated fatty acids and meat may
      increase the risk of IPF.

PMID- 16562717
TI  - Real-time PCR assay for improved detection of Mycobacterium tuberculosis complex
      in paraffin-embedded tissues.
AB  - OBJECTIVE: To test the usefulness of a commercially available real-time
      polymerase chain reaction (PCR) kit for the detection of Mycobacterium
      tuberculosis complex (MTBC) in formalin-fixed, paraffin-embedded tissues.
      RESULTS: The examination of 24 specimens of patients with a final diagnosis of TB
      shows that the real-time PCR assay exhibits a higher sensitivity (66.7%) for the
      detection of MTBC DNA than an alternative in-house IS6110 PCR (33.3%), whereas
      staining detected acid-fast bacilli in only two cases (8.3%). CONCLUSION: The
      real-time PCR assay provides a highly sensitive and specific means for the
      detection of MTBC DNA in histopathological specimens.

PMID- 16562718
TI  - Yield of pulmonary tuberculosis cases by employing two screening methods in a
      community survey.
AB  - OBJECTIVE: To compare the yield of tuberculosis (TB) cases by two screening
      methods. SETTING: Two disease surveys conducted in Tiruvallur, south India.
      RESULTS: Of bacteriologically confirmed cases, 60% were identified by symptom
      inquiry alone whereas 82% were identified using chest radiography (CXR).
      CONCLUSION: The prevalence of TB was underestimated by both methods. The total
      cases in this community can be estimated by multiplying the number of identified
      cases by a correction factor (CF) of 1.7 when symptom inquiry alone is used or
      1.2 when CXR is used. The CF may be different in other settings.

PMID- 16562719
TI  - Trend in the prevalence of TB infection and ARTI after implementation of a DOTS
      programme in south India.
AB  - OBJECTIVE: To estimate the risk of tuberculosis (TB) infection among children <10
      years and assess the impact of a DOTS-based programme. SETTING: After DOTS
      implementation in Tiruvallur district, south India, we undertook three tuberculin
      surveys and estimated the ARTI among children aged <10 years. RESULTS: The ARTI
      estimates in the three tuberculin surveys were 1.6%, 1.4% and 1.2%, respectively.
      There was a significant decline in the trend of TB infection (P < 0.001). The
      annual decline estimated from the first to the third survey was 6%. CONCLUSION:
      DOTS implementation was associated with a substantial reduction in the risk of TB
      infection among children.

PMID- 16562720
TI  - Pulmonary tuberculosis due to Mycobacterium bovis in Leon.
AB  - In recent years, human infection due to Mycobacterium bovis has been considered
      almost eradicated in most industrialised countries. During the period 1998-2002,
      nine patients were diagnosed with pulmonary tuberculosis (TB) due to M. bovis in
      the Hospital Monte San Isidro, Leon, Spain. Their average age was 66 years. The
      response to therapy was good in seven cases, while two died, one from renal TB
      and the other from cancer of the pancreatic head.

PMID- 16562721
TI  - Rhodococcus and Mycobacterium Tuberculosis: masquerade or mixed infection.
AB  - Rhodocci have a morphology similar to that of Mycobacterium tuberculosis (TB),
      and are indistinguishable from normal diphtheroid flora. Symptoms include fever,
      productive/non-productive cough and pleuritic chest pain. Rhodococcal infections,
      being resistant to routine anti-tuberculosis medications, may be misdiagnosed as
      drug-resistant TB, thus prompting treatment for TB with rifampicin-containing
      regimens that promote the emergence of resistance. We present here a sputum smear
      AFB-positive case who, although clinically cured, remains unresolved despite a
      series of technological investigations as to the cause of infection being purely
      rhodococci or mixed infection with M. tuberculosis.

PMID- 16562722
TI  - Quality in TB control.

PMID- 16562723
TI  - [Treatment of parturient paresis with high-dose calcium].
AB  - The goal of the present study was to evaluate a calcium dose that was higher than
      the conventional dose for treatment of parturient paresis in cows. Thirty cows
      with parturient paresis received 1000 ml of 40 per cent calcium borogluconate
      solution supplemented with 6 per cent magnesium hypophosphite. Cows in group A
      received 200 ml of the solution intravenously over a 10-minute period, and the
      remaining 800 ml via a slow intravenous drip over a six-hour period. Cows in
      group B received 500 ml of the solution intravenously over a 20-minute period,
      and the remaining 500 ml via a slow intravenous drip over a six-hour period.
      Afterwards, the cows were monitored continuously and examined every hour for
      eight hours. Samples of blood were collected from all the cows before treatment
      and at 10, 20, 40, 60, 90, 120, 180, 240, 300, 360, 420 and 480 minutes and 24,
      48 and 72 hours after treatment. The concentrations of total calcium, ionised
      calcium, inorganic phosphorus and magnesium were determined. Cows that did not
      stand within 12 hours of treatment received one or more additional treatments.
      There was no significant difference in the recovery rate between the two groups.
      Of the 30 cows, 14 (47 per cent) rised after one treatment and 15 others (50 per
      cent) were cured after two or more treatments. One cow did not respond to
      repeated treatments and was euthanased four days after the start of treatment.
      The results of electrolyte analyses before treatment did not differ significantly
      between the two groups. In 27 (90 per cent) cows, the concentrations of calcium
      and inorganic phosphorus were lower than normal and in 3 (10 per cent) cows, only
      the concentration of inorganic phosphorus was lower than normal. The
      concentration of total calcium increased markedly ten minutes after the start of
      treatment in both groups, and at eight hours, the mean concentration of calcium
      was within the normal range. At 24 and 48 hours, the mean concentration of
      calcium was below normal, but at 72 hours it was again within the normal range.
      The concentration of inorganic phosphorus increased slowly in both groups,
      although it was not within the normal range at eight hours. In both groups, it
      achieved normal values at 24, 48 and 72 hours. The mean electrolyte
      concentrations did not differ significantly at any measuring point between cows
      that stood within eight hours of treatment and those that did not. Our results
      indicate that increasing the dose of calcium administered does not improve the
      recovery rate of cows with parturient paresis.

PMID- 16562724
TI  - [Diabetes mellitus in the cat: a review].
AB  - About 80% of diabetic cats suffer from type 2 diabetes which is characterized by
      reduced insulin secretion from beta-cells and by insulin resistance. As in humans
      cats experienced a change in life habits and eating conditions over the last
      years leading to a tremendous increase in the prevalence of obesity. In both
      species obesity is one of the major risk factors for the development of type 2
      diabetes. Treatment should be initiated immediately after diagnosis. In Zurich,
      therapy consists of application of an intermediate-acting insulin and dietary
      management. In the latter the use of diets with reduced carbohydrate content
      seems to be of utmost importance. We recently found that the percentage of cats
      with a transient course of diabetes increases from previous 25% to 50-70% when a
      diet with strongly reduced carbohydrate content is fed.

PMID- 16562725
TI  - [Feline hemoplasmas in Switzerland: identification of a novel species, diagnosis,
      prevalence, and clinical importance].
AB  - Two feline hemotropic mycoplasma spp. (aka hemoplasma) have previously been
      recognized. We recently discovered a third novel species in a cat with hemolytic
      anemia, designated 'Candidatus Mycoplasma turicensis', which is closely related
      to rodent haemoplasmas. This novel species induced anemia after experimental
      transmission to two SPF cats. Three quantitative real-time PCR assays were newly
      designed and applied to an epidemiological study surveying the Swiss pet cat
      population. Blood samples from 713 healthy and ill cats were analyzed. Up to 104
      parameters per cat (detailed questionnaire, case history, laboratory parameters
      and retroviral infections) were evaluated. 'Candidatus Mycoplasma haemominutum'
      infection was more prevalent (8.5%) than Mycoplasma haemofelis (0.5%) and
      'Candidatus Mycoplasma turicensis' (1%). Hemoplasma infections were associated
      with male gender, outdoor access, and old age, but not with disease or anemia.
      Infections were more frequently found in the South and West of Switzerland.
      Several hemoplasma infected cats, some acutely infected, others co-infected with
      FIV or FeLV, showed hemolytic anemia indicating that additional factors might
      play a role in the pathogenesis of the disease.

PMID- 16562726
TI  - [Piroplasms of ruminants in Switzerland and zoonotic significance of Babesia].
AB  - Piroplasms are tick-transmitted blood parasites belonging to the genera Babesia
      and Theileria. In western and southern Switzerland, B. divergens, a small Babesia
      species, has been known for a long time as a parasite of cattle. Recent
      investigations have revealed the autochthonous occurrence of this parasite also
      in central and eastern Switzerland. On the occasion of an outbreak of
      anaplasmosis in the canton of Grisons, however, B. bigemina, a large Babesia
      species, and Theileria of the buffeli/sergenti/orientalis species complex were
      for the first time identified; the epidemiology of these two piroplasms in
      Switzerland remains unknown until now. The recent identification by genetic
      analyses of B. divergens in wild ruminants contradicts the hitherto postulated
      strict host specificity of this Babesia species for cattle. B. divergens as well
      as the closely related Babesia spp. genotype EU1 have in single cases also been
      identified in splenectomized humans. The rodent babesia B. microti which causes a
      human infection that is considered an "emerging tick-borne disease" in the
      U.S.A., is widespread in rodent populations in Switzerland, but seems to be of
      minor relevance as zoonotic pathogen here. Reasons for this could be differences
      in virulence of the parasites or in the transmission by the respective tick
      vectors on the two continents.

PMID- 16562727
TI  - Initial clinical impressions of the U.C. Davis large animal lift and its use in
      recumbent equine patients.
AB  - The U.C. Davis Large Animal Lift (LAL) is a lightweight sling developed to help
      lift horses in clinical and rescue situations. Here we report on its first use in
      16 recumbent horses with neurologic, muscular and musculoskeletal disorders. For
      each horse, history, sedation, ease and time of LAL application and hoisting,
      standing ability, LAL tolerance and outcome were recorded. The LAL was easily and
      safely applied in all horses in less than five minutes and the procedure was well
      tolerated with minimal to no sedation. While 10 horses were able to stand in the
      LAL after being hoisted, 6 horses were unable to stand and were eventually
      euthanized due to the inability to regain weight bearing function. The LAL has
      shown to be a useful devise to evaluate the standing ability of recumbent horses
      and can be used alone or in combination with the Anderson Sling Support Devise to
      allow standing support of horses with a variety of debilitating problems.

PMID- 16562728
TI  - Seroprevalence of Toxoplasma gondii infection in goats and sheep in Zimbabwe.
AB  - Seroprevalence rates of Toxoplasma gondii anti-antibodies in adult goats and
      sheep from different parts of Zimbabwe were determined. A total of 225 (67.9%) of
      the 335 serum samples tested were positive for anti-T. gondii IgG antibodies with
      the indirect fluorescent antibody test. There were differences in antibody
      seroprevalences among communal land goats from the different agro-ecological
      zones (Natural regions llb and III: 80 and 96.7%, respectively; Natural region
      IV: 65.9%; Natural region V: 45%; and Natural region III had a significantly
      higher seroprevalence than IV and V. The highest seroprevalences found in Natural
      regions II b and Ill are likely to be linked to the existence of more households
      and hence the possibility of a higher concentration of domestic cats that
      increases the chances of environmental contamination with their faeces harbouring
      T. gondii oocysts. The seroprevalence rate in sheep from a large commercial farm
      (10%) was significantly lower than that of sheep reared under the communal
      grazing system (80%). Overall, significantly higher proportions of seropositive
      animals had antibody titres of 1:50 (34.2% of 225) and 1:100 (44% of 225) as
      compared to the 9.8% and 12% with antibody titres of 1:200 and > or =1:400,
      respectively.

PMID- 16562729
TI  - Electrocardiographic surrogates of structural myocardial alterations in the
      Dorper sheep heart.
AB  - In this study we evaluated the validity of well-known human electrocardiographic
      markers of myocardial pathology in Dorper sheep. These markers include: the
      duration of the QRS complex of premature ventricular complexes (PVCs), the
      presence of notching of the QRS complex of PVCs and change of the ST-segment of
      PVCs. It was shown that these three electrocardiographic phenomena correlate with
      myocardial pathology in the hearts of Dorper sheep. We also describe a new
      electrocardiographic indicator of myocardial pathology, namely an increase in the
      frequency of cardiac memory T waves as a new electrocardiographic surrogate for
      myocardial pathology in the hearts of Dorper sheep.

PMID- 16562730
TI  - Association of trypanosomosis risk with dairy cattle production in western Kenya.
AB  - Dairy cattle reared in western Kenya are exposed to medium to high levels of
      trypanosomosis risk. The social background, farm characteristics and dairy cattle
      productivity of 90 and 30 randomly selected farmers from medium- and high-risk
      trypanosomosis areas, respectively, were compared. All the 120 farmers were
      visited between July and August 2002. Data analysis was performed using
      descriptive statistics and analysis of variance. The results showed that
      increased trypanosomosis risk represented by an increase in disease prevalence in
      cattle of 1% to 20% decreased the density of dairy cattle by 53% and increased
      the calving interval from 14 to 25 months. The increased risk was also associated
      with a significant increase in cattle mortalities and in a lactation period of
      257 to 300 days. It was concluded that removal of the trypanosomosis constraint
      on dairy production would lead to expansion of dairying since the domestic demand
      for dairy products is expected to increase.

PMID- 16562731
TI  - Discrimination between sheep-associated and wildebeest-associated malignant
      catarrhal fever virus by means of a single-tube duplex nested PCR.
AB  - A single-tube duplex nested polymerase chain reaction (sdn-PCR) was developed for
      the detection of and discrimination between ovine herpesvirus-2 (OvHV-2) and
      alcelaphine herpesvirus-1 (AIHV-1). These viruses respectively cause sheep- and
      wildebeest-associated malignant catarrhal fever (SA-MCF and WA-MCF). In the first
      step of the sdn-PCR, two primers with high annealing temperatures based on
      conserved regions of the tegument genes were used for DNA amplification. In the
      second step, two primer sets based on variable regions of the respective OvHV-2
      and AIHV-1 genes and with annealing temperatures > 11 degrees C below the primers
      used in the first step, were used. Internal regions of different sizes from
      amplicons produced in the first step were amplified. This single-tube test
      obviates the need for two separate assays to detect both viral types, thereby
      reducing time, labour and cost.

PMID- 16562732
TI  - Elephant shrews as hosts of immature ixodid ticks.
AB  - Two hundred and seventy-three elephant shrews, consisting of 193 Elephantulus
      myurus, 67 Elephantulus edwardii and 13 animals belonging to other species, were
      examined for ixodid ticks at 18 localities in South Africa and Namibia. The
      immature stages of Ixodes rubicundus, Rhipicentor nuttalli, Rhipicephalus
      warburtoni and a Rhipicephalus pravus-like tick were the most numerous of the 18
      tick species recovered. Substantial numbers of immature Rhipicephalus arnoldi,
      Rhipicephalus distinctus and Rhipicephalus exophthalmos were also collected from
      elephant shrews at particular localities. Larvae of I. rubicundus were most
      numerous on E. myurus in Free State Province from April to July and nymphs from
      June to October. Larvae of R. nuttalli were most numerous on these animals during
      April, May, August and September, and nymphs in February and from April to
      August. The immature stages of R. warburtoni were collected from E. myurus only
      in Free State Province, and larvae were generally most numerous from December to
      August and nymphs from April to October.

PMID- 16562733
TI  - Natural infection rates and transmission of Theileria annulata by Hyalomma
      anatolicum anatolicum ticks in the Sudan.
AB  - Hyalomma anatolicum anatolicum nymphs were collected from two localities in the
      Sudan: Eddamer in Northern Sudan and Wad-Medani in Central Sudan. They were
      allowed to moult to adult ticks, which were assessed for Theileria infection in
      their salivary glands using Feulgen stain. At Eddamer, 49.6% of 123 ticks
      examined were infected with Theileria and the mean intensity of infection was 1.3
      (i.e. the number of infected acini/number of infected ticks). At Wad-Medani, 8.6%
      of 162 ticks were infected and the mean intensity of infection was 7.9. The
      prevalence of infection was higher in female than in male ticks at both
      localities. When adult H. a. anatolicum were applied onto two susceptible calves,
      both animals developed the severe form of theileriosis.

PMID- 16562734
TI  - Acaricide efficiency of amitraz/cypermethrin and abamectin pour-on preparations
      in game.
AB  - The efficacy of an amitraz/cypermethrin pour-on preparation (1% w/v each) was
      tested against natural tick infestations of buffaloes, eland and blesbok in three
      separate trials. The eland were also treated with a 0.02% abamectin (w/v)
      acaricidal pour-on preparation. The amitraz/cypermethrin pour-on was effective
      against Amblyomma hebraeum, Rhipicephalus evertsi evertsi, Rhipicephalus
      appendiculatus and Hyalomma marginatum rufipes on the buffaloes. Both acaricides
      were effective against R. appendiculatus and Rhipicephalus (Boophilus)
      decoloratus in the eland. The amitraz/cypermethrin acaricide was effective
      against R. (Boophilus) decoloratus in the blesbok. Ticks can cause damage to the
      skins, secondary infections, abscesses, anaemia, loss of condition, tick
      toxicosis and act as vectors of infectious diseases. Introduction of hosts and/or
      ticks from endemic to non-endemic areas because of translocation of game, may
      lead to severe losses. The pouron acaricides tested were effective against
      natural tick infestations and should always be used according to the
      manufacturer's instructions and efficacy claims.

PMID- 16562735
TI  - Parasites of domestic and wild animals in South Africa. XLVI. Oestrid fly larvae
      of sheep, goats, springbok and black wildebeest in the Eastern Cape Province.
AB  - Merino sheep in Thornveld, Dorper sheep and Angora goats in inland Valley
      Bushveld, Angora goats and Boer goats in Valley Bushveld on the coastal plateau,
      and springbok, Antidorcas marsupialis, and black wildebeest, Connochaetes gnou,
      in Karroid Mountainveld, all in the Eastern Cape Province, were examined for the
      larvae of nasal bot flies. The sheep and goats were infested with the larvae of
      Oestrus ovis, and Dorper sheep and Boer goats harboured more larvae than Angora
      goats on the same farms. Most infestation was present from November to May in
      Merino sheep in Thornveld, from February to June in Dorper sheep in inland Valley
      Bushveld, and from May to September in Angora and Boer goats in Valley Bushveld
      on the coastal plateau. These patterns of seasonality appeared to be regulated by
      the severity of the summer temperatures at the various localities. The springbok
      were infested with the larvae of Rhinoestrus antidorcitis, most of which seemed
      to mature from June to August. All larval sages of Oestrus variolosus and
      Gedoelstia hassleri were present in the black wildebeest, and large numbers of
      1st instar larvae of G. hassleri appeared to accumulate on the dura of the
      wildebeest from June to August.

PMID- 16562736
TI  - A macro- and light microscopical study of the pathology of Calicophoron
      microbothrium infection in experimentally infected cattle.
AB  - Twelve Tuli weaner steers aged 1 year were randomly subdivided into three groups
      of four animals and infected with different doses of Calicophoron microbothrium
      metacercariae. Each animal in Group I received a low dose (LD) of 5 000
      metacercariae, Group II a medium dose (MD) of 15 000 metacercariae, Group III a
      high dose (HD) of 25 000 metacercariae and one additional animal was kept as an
      uninfected control (C). After infection, one animal from each group was
      slaughtered on Day 28, 42, 56 and 84 post infection (pi) and samples from the
      ileum, jejunum, duodenum, abomasum and the rumen were collected for
      histopathological and cytological examination. On Day 28 pi, the gross
      pathological lesions observed in the duodenum of the LD and the MD animals were
      similar and comprised duodenal thickening, corrugation, hyperaemia, petechiation
      and ulceration. In the HD animal the duodenal lesions were similar but more
      severe. The abomasal folds were severely oedematous in the MD group and nearly
      occluded the abomasal lumen. Moderate oedema of the abomasal folds was also
      present in the LD and HD animals. The gross pathological lesions regressed in all
      the infected groups with increasing age of infection and had disappeared
      completely by Day 56 pi. On Day 28 pi the histopathological lesions in the
      duodenum and jejunum of the LD and MD groups were similar, comprising subtotal
      villous atrophy, hyperplasia of Brunner's glands and Peyer's patches and moderate
      infiltration of eosinophils, mast cells and a few globule leukocytes, basophils
      and lymphocytes in the lamina propria. The HD group had total villous atrophy,
      severe hyperplasia and cystic dilatation of Brunner's glands, which had expanded
      to cover the entire submucosa. On Day 42 pi the histopathological lesions were
      still present in the MD and the HD groups comprising subtotal villous atrophy and
      hyperplasia of Brunner's glands. Heavy infiltrations of eosinophils, moderate
      amounts of mast cells and a few basophils, globule leukocytes and lymphocytes
      were still present in the lamina propria of all three groups. On Day 56 pi, a few
      glands were still cystic in the MD and the HD groups. Moderate cell infiltrations
      were still present in the lamina propria of all the three groups and by Day 84 pi
      complete regeneration had occurred in all animals.

PMID- 16562737
TI  - The susceptibility of Trypanosoma congolense isolated in Zambezia Province,
      Mozambique, to isometamidium chloride, diminazene aceturate and homidium
      chloride.
AB  - Resistance to trypanocidal drugs has been detected in various African countries
      and is a serious impediment to the control of livestock trypanosomosis. To
      determine whether drug resistant trypanosome strains are present in the Zambezia
      Province of Mozambique a study was initiated. To assess the effect of the farming
      system and the drug-use regimen on the development of drug resistance,
      trypanosome isolates were collected from cattle from subsistence and commercial
      livestock production systems. The susceptibility of seven isolates against
      isometamidium chloride, diminazene aceturate and homidium chloride was tested in
      mice using a multiple-dose test. In four of the seven isolates high levels of
      drug resistance to diminazene aceturate and isometamidium chloride were detected.
      In most cases the observed levels of drug resistance correlated with the drug-use
      practices in the particular livestock production system.

PMID- 16562738
TI  - Ticks on crested francolins, Francolinus sephaena, and on the vegetation on a
      farm in Limpopo Province, South Africa.
AB  - Ticks were collected at approximately bi-monthly intervals between June 1996 and
      June 1997 from crested francolins, Francolinus sephaena, and from the vegetation
      on a mixed cattle and wildlife farm in Limpopo Province, South Africa. The birds
      were infested with the immature stages of 13 tick species, of which Amblyomma
      hebraeum, Amblyomma marmoreum and Hyalomma marginatum rufipes were the most
      numerous and prevalent. Ten ixodid tick species were collected from the
      vegetation, of which the immature stages of Rhipicephalus appendiculatus,
      Rhipicephalus (Boophilus) decoloratus and Rhipicephalus evertsi evertsi were the
      most numerous. No adult ticks were collected from the birds and only two from the
      vegetation. The restricted home range of crested francolins implies that they
      could serve as a source of tick infestation only for other animals within the
      same habitat as the birds.

PMID- 16562739
TI  - [Intestinal cryptosporidiosis at an early age and its negative consequences].
AB  - This review calls the attention of physicians, primarily pediatricians, to
      cryptosporidiosis, a still little known intestinal infection caused by the
      protozoan pathogen Cryptosporidium parvum (Coccidia, Sporozoa). By using 10--14
      day rats as a model, the authors have first provided evidence that even 4-day
      intestinal cryptosporidiosis may trigger obvious negative changes in the liver
      and heart, i.e. in the organs where the parasite does not develop. In the
      infected rats, growth retardation was registered, in addition to liver
      hypertrophy and partial heart atrophy, and growth retardation. Light and electron
      microscopies, absorption and fluorescence cytometry, quantitative morphometry,
      and image analysis were applied. In both hepatocytes and cardiomyocytes, the
      polyploid cell fraction was seen much increased, with the occurrence of 4c, 8c,
      and even 16c nuclei. Besides, in the hepatocytes, the amount of glycogen
      decreased whereas the level of protein increased, along with enhanced nucleolar
      activity in the nuclei. Unlike, the cardiomyocytes of the infected rats were
      characterized by protein decrease, in addition to almost two-fold cell body
      elongation. This is the first documented evidence for serious pathological
      changes in the extraintestinal organs, caused by the intestinal pathogen C.
      parvum. Within the first 4 days of infection, both the liver and heart of the
      host seem to work under stress. It is plausible that on modulating liver and
      heart ploidy, the intestinal parasitic infection (cryptosporidiosis) may bring
      about functional impairments of these organs, untypical of early age, leading
      eventually to long-term consequences in further life of formerly infected
      individuals.

PMID- 16562740
TI  - [The clinical and functional status of the pancreas in patients with psoriasis
      concurrent with chronic opisthorchiasis].
AB  - Seventy patents including 30 with psoriasis concurrent with chronic
      opisthorchiasis, 20 with psoriasis without opisthorchiasis, and 20 with chronic
      opisthorchiasis, were examined. Structural changes in the pancreas and its
      endocrine and exocrine functions were evaluated. Patients with psoriasis alone or
      in combination with chronic opisthorchiasis were found to have signs of
      pancreatic lesion with its impaired endocrine and exocrine functions. These
      impairments are more pronounced in the group of patients with mixed pathology.

PMID- 16562741
TI  - [Clinical analysis of autonomic nervous system disorders in patients with
      psoriasis concurrent with chronic opisthorchiasis].
AB  - The study was undertaken to detect the characteristics of autonomic nervous
      system disorders in patients with psoriasis concurrent with chronic
      opisthorchiasis and, on their basis, to develop therapeutic manipulations.
      Examinations were made in 150 patients with psoriasis concurrent with chronic
      opisthorchiasis, 100 psoriatic patients without helminthiasis, 100 patients with
      chronic opisthorchiasis, and 30 healthy individuals. The questionnaire method
      developed and recommended for use by the All-Union Center of Autonomic Nervous
      System Diseases was employed for the screening diagnosis of vegetative dystonia
      syndrome and for the estimation of its severity. The vegetative dystonia syndrome
      was observed in all patients with psoriasis concurrent with chronic
      opisthorchiasis. There was an association of the vegetative dystonia syndrome
      with the area of skin involvement, the severity of psoriasis, the duration of the
      latter and opisthorchiasis.

PMID- 16562742
TI  - [Immunoglobulin E (IgE) in the blood and the diagnosis of hepatic
      echinococciasis].
AB  - The paper presents the results of a study of the significance of IgE in the
      diagnosis of echinococciasis. Preoperative examinations of patients with showed
      the increased serum concentrations of IgE. The decreased concentration of IgE was
      recorded on postoperative day 20. Enzyme immunoassay used to measure serum IgE
      concentrations is a sensitive technique for the diagnosis of hepatic
      echinococciasis and for the prognosis of allergic reactions and diseases.

PMID- 16562743
TI  - [Parasitic carriage of the causative agents of tropical malaria].
AB  - In 1993 to 1999, a total of 1020 Russians temporarily living in the Republic of
      Guinea were examined; of them 26 (2.5%) persons were found to be asymptomatic
      carriers of P. falciparum. Single studies of cellular and humoral immunity were
      first conducted in 15 asymptomatic parasitic carriers of P. falciparum.
      Asymptomatic parasitic carriage of P. falciparum was established in nonimmune
      persons who developed immunopathological reactions. The nature of immune
      disorders gives grounds to regard parasitic carriage as a subclinical form of
      tropical malaria for the first time. By taking into account asymptomatic carriage
      of P. falciparum, a parasitological blood study should be made in all non-immune
      persons when they are leaving an endemic focus for Russia.

PMID- 16562744
TI  - [An outbreak of Plasmodium vivax malaria in Kyrghyzstan].
AB  - Malaria was not notified in the republic in 1960 to 1982, with exception of 1963
      where one case of imported malaria was identified. Twenty-four cases of locally
      transmitted malaria were detected, 11 of them being registered in the Batken
      district, Osh Region, contiguous with Tadjikistan and Uzbekistan. In 1981 to
      2000, a total of 101 cases of malaria were notified, in 2001 there was an
      increase in cases of malaria to 136, while in 2002, a total of 2744 cases of
      malaria were registered mainly in the Fergana valley. Malaria was imported from
      Tadjikistan, Azerbaijan, Uzbekistan, and Afghanistan. The infectious agent of
      malaria was P. vivax in 98% of cases and P. falciparum in 2%. The high malarial
      potential areas are the Osh, Zhalalabat, and Batken Regions and town of Osh. In
      2002, the investigators identified patients with malaria, made its chloroquine
      eliminating treatment, seasonal chemoprevention of some 5000 dwellers of the
      Leilek District of the Batken Region contiguous with Tadjikistan, and larvicidal
      treatments of water reservoirs and rice checks with dimilin. Almost 1,988,000 m2
      of premises were treated with Solfac. Mosquito fishes were placed into more water
      reservoirs in 2003. In 2003 there was a tendency for a decrease in the incidence
      of malaria, as compared with 2002, which may be ascribed to the small size of
      vectors, which is due to the cold spring and cool June and July. In 2003, there
      were treatments of premises, mosquito fish enrichment of water reservoirs,
      interseasonal chemoprophylaxis of patients who experienced malaria in 2002;
      impregnated bed curtains were available to protect the dwellers of foci from
      mosquito bites.

PMID- 16562745
TI  - [The epidemiological and clinicoimmunological aspects of the outburst of
      trichinosis in the Krymsky District of the Krasnodar Territory].
AB  - The present paper presents the epidemiological and clinicoimmunological aspects
      of the outburst of trichinosis in the Krymsky District of the Krasnodar Territory
      in January 2001. Six hundred and forty-eight persons ate infested wild boar meat,
      119 (74.8%) fell ill with moderate and severe trichinosis. The authors provide
      the results of 3.5-year immunological studies of the patients with trichinosis
      and convalescents, infection-risk and healthy individuals; those of autopsies of
      the corpses of those who died from accidental causes unassociated with
      trichinosis, as well as examinations of domestic, synanthropic, and wild animals.
      The findings indicate that there is a focus of trichinosis with the low level of
      endemia in the Krymsky District of the Krasnodar Territory.

PMID- 16562746
TI  - [The malaria mosquitoes (Diptera, Culicidae, Anopheles) of the Amudarya river
      valley].
AB  - Five malaria mosquitoes were identified in the Amudarya river valley. An.
      pulcherrimus, An. martinius, An. superpictus, and An. hyrcanus inhabit in the
      plain of the valley. An. superpictus, An. pulcherrimus, An. hyrcanus, and An.
      claviger occur in the head of the Amudarya river. The nucleotide composition of
      the second inner transcribed spacer (ITS2) of ribosomal DNA and the locus of
      cytochromoxidase I (COI) of mitochondrial DNA was determined in the closely
      related species An. martinius and An. artemievi. It is shown that the loci in
      question may be used to diagnose twin species of the maculipennis complex.

PMID- 16562747
TI  - [The species composition of mosquitoes and ticks in Armenia].
AB  - Comprehensive epidemiological, entomological, virological, and parasitological
      studies were conducted to examine the species composition and size of
      bloodsucking arthropoda (mosquitoes and ticks). A total of 64,567 mosquitoes and
      45,180 Ixodes ticks were collected. Among the mosquitoes, Anopheles maculipennis
      was a prevalent species (81.6%). In all climatic zones, Dermacentor marginatus
      was the largest in number and most abundant during flag collections from cattle
      and plants (62.5% and 95.5%, respectively). Virological studies of the collected
      field material identified 125 strains of arboviruses belonging to 10 viruses:
      Tyaginya, Sindbis, Batai, Dkhori, tick-borne encephalitis, West Nile fever,
      Tamdy, KGL, Geta, and Bkhandzha. The identified arboviruses are environmentally
      associated with both mosquitoes and ticks. The larger number and diversity of
      bloodsucking artropoda present a potential risk of outbursts of arbovirus
      infections on the territory of the republic.

PMID- 16562748
TI  - [The mammals of Guinea as reservoirs and carriers of arboviruses].
AB  - A great body of data on the fauna and ecology of wild mammals and their
      participation in the circulation of arboviruses were collected when the ecology
      of the latter of the Republic of Guinea was studied in 1978 to 1989. A hundred
      and eighteen species belonging to 10 orders were identified. Over 2,000
      biological specimens were virologically and serologically examined. Six
      arboviruses were isolated. These included Dugbe virus (from the hussar monkey
      Cercopithecus (Erythrocebus patas) and 5 viruses from chiropters: Rift valley
      fever, from Micropteropus pusillus, Miniopterus schreibersi, and Hipposideros
      caffer, Saboya, Fomede, and Ank 6909 from Nycteris gambiensis and Kolenter from
      Hipposideros sp. Fomede, Kolente, and Ank 6909 viruses turned out to be new
      species for science. Rodents were found to have viral antigens of Lass fever
      (Mastomys natalensis, Tatera valida kempi and Rattus rattus), Dugbe and
      Chikungunya fevers (M. natalensis) and West Nile fever (Mus sp.). A serological
      survey of mammals revealed that the latter had antibodies to 12 arboviruses.
      Thus, the mammals of Guinea participate in the circulation of 18 arboviruses, 13
      of them are pathogenic for man.

PMID- 16562749
TI  - [New evidence for mass reproduction of midges (Diptera, Simuliidae) in the
      Voronezh Region].
AB  - In the forest-steppe zones, the bloodsucking dipterans--midges (Diptera,
      Simuliidae)--tend to drastically increase in size, which poses medical and
      veterinary problems (the toxic saliva administered into the victim's body on
      blood sucking causes diseases in man, disability, and even animals' death).
      According to our data, the role of dominating bloodsuckers varies in different
      districts of the Voronezh Region, depending on their Iocal conditions (the types
      of water systems and landscapes).

PMID- 16562750
TI  - [Influence of environmental factors on the infection rates of fishes and
      shellfishes by trematodes of the Opisthorchidae family in the Krotovaya Lyaga
      Lake].
AB  - The relationship of the annual trends in the infection of crucians (Carassius
      carassius) (L.) with Opisthorchis felineus metacercariae, in that of verkhovkas
      (Leucasplius delineatus) (Hackel), and in that of lake minnows (Phoxinus
      percnurus) (L.) with O. felineus and Metorchis billis to the environmental
      factors under natural fluctuations of the level of water and under the man-made
      effects on the water regime of the reservoir was studied. When the level of water
      naturally changes, the infection of crucians with Metorchis was found to be
      affected by their size, water temperature, and environmental pH values, and the
      human Opisthorchis affliction depends on the severity of infection of commercial
      sized crucians by metacercariae. The infestation of the verkhovka was determined
      by the temperature of water and that of the lake minnow was by its size and the
      increased areas of the lake with the depths salubrious to its existence. With man
      made effects (dewatering for watering agricultural lands) on the water regime of
      the reservoir, the infestation of the lake minnow depended on its size in the
      shallow water and on the level of water. Environmental factors, such as pH
      values, the area of shallow waters, and the size of mollusks, positively affected
      the higher extensiveness of infestation of mollusks with the parthenitae of
      opisthorchid flukes.

PMID- 16562751
TI  - [Survival of helminth eggs in the wastewater mud in the sludge beds of Chita
      waterworks].
AB  - The species composition, size, and survival of human and domestic animal helminth
      eggs was determined in the wastewater mud in the sludge beds of the waterworks of
      Chita. It was shown that when the wastewater mud was little dried in the sludge
      beds under distinctly continental climatic conditions for three years, their
      complete disinvasion did not take place. The eggs of seat-worms (Enterobius
      vermicularis), whipworms (Trichuris trichiura), broad tapeworms (Diphylobotrium
      latum), and teniae were undetectable in the mud samples after the second and
      third year of drying. Surviving Ascaris eggs may develop in the soil to the
      invasion stage under the climatic conditions of Chita, by creating a risk for new
      infections.

PMID- 16562752
TI  - [The manifestation of necrophagy in the populations of rodents carrying the virus
      of hemorrhagic fever with renal syndrome].
AB  - The role of necrophagy in the epizootic manifestations of hemorrhagic fever with
      renal syndrome (HFRS) is first shown. By analyzing a great body of data obtained
      in the Saratov Region in 1982-2000, it has been established that the frequency of
      manifestations of necrophagy depends on many factors, the most important of which
      are a season, the size (density) of populations of small mammals, their species
      composition and the type of biotopes inhabited by these animals. Necrophagy is
      ascertained to be of great importance in HFRS foci as one of the alimentary
      routes of infection transmission in the parasitic systems. The presence or
      absence of necrophagy may serve as a preliminary test for the activity of HFRS
      foci.

PMID- 16562753
TI  - [Studies of gadflies from the Arctic North of Russia over years (1904-2004)].

PMID- 16562754
TI  - [Estimation of the spectrum of antihelminthic activity of VIVALIN (VIG-08)].

PMID- 16562755
TI  - [The bloodsucking mosquitoes (Culicidae) of North Afghanistan].
AB  - Up to date, the fauna of bloodsucking mosquitoes in North Afghanistan remains to
      be almost unstudied so far. To the known mosquito species (Anopheles
      pulcherrimus, An. algeriensis, An. hyrcanus, An. claviger, An. habibi, and An.
      superpictus), the author added two more species Culex pipiens and Aedes caspius
      caught during field trials in the localities of the Kunduz Province of the
      Islamic republic of Afghanistan in April 2005.

PMID- 16562756
TI  - [Pneumocystis carini infection in patients with HIV/AIDS in the Republic of
      Armenia].

PMID- 16562757
TI  - Just fix the problem.

PMID- 16562758
TI  - Call to action: Adult immunization.

PMID- 16562759
TI  - Technique in question.

PMID- 16562760
TI  - Electronic health records: a growing trend towards increased efficiency.

PMID- 16562761
TI  - Antibiotic prescribing in Arkansas: compliance with national standards varies
      widely.

PMID- 16562762
TI  - Tularemia induced bilateral optic neuritis.

PMID- 16562763
TI  - Insulinoma: diagnosis and localization procedures.
AB  - A 26-year-old Hispanic woman presented for evaluation of hypoglycemia documented
      by plasma glucose of 38mg/dl. A supervised 72-hour fasting test showed a plasma
      glucose of 30 mg/dl, insulin of 11 ulU/ml, proinsulin of 16.8 pmol/L and C
      peptide 2.3 ng/ml after 16 hours of fasting. Sulfonylurea screen was negative.
      MRI showed a 12mm mass in the head of the pancreas. The tumor was resected and
      pathology was consistent with an insulinoma. The patient has been asymptomatic
      postoperatively with no hypoglycemia on repeat fasting. We reviewed here the
      different modalities for preoperative localization of insulinoma.

PMID- 16562765
TI  - Political will?

PMID- 16562764
TI  - Globalisation has not only raised expectations of economic growth, but created an
      interdependence which will determine our future well-being.

PMID- 16562766
TI  - Brain drain in the health sector: beyond band-aid solutions.

PMID- 16562767
TI  - Mediating equity in global health: a proposal.

PMID- 16562768
TI  - Peak oil, climate change, public health and well-being.

PMID- 16562769
TI  - The Asian tsunami one year later: public health, a disaster within a disaster.

PMID- 16562770
TI  - Emergency management and public health systems.

PMID- 16562771
TI  - Water, sanitation and hygiene: health 101.

PMID- 16562772
TI  - Vaccinations for Hajj.

PMID- 16562773
TI  - Housing and health in Havana, Cuba.

PMID- 16562774
TI  - The health and safety crossroads: are we about to take the wrong turn?

PMID- 16562775
TI  - A review of major influences on current public health policy in developed
      countries in the second half of the 20th century.
AB  - Public health policy underwent substantial transformation during the latter half
      of the 20th century. The landmark statement was the 1948 World Health
      Organization (WHO) constitution, which identified good health as a fundamental
      right and gave the responsibility to governments to achieve it for all their
      people. However, following World War II, developed countries made substantial
      investment in health care with less attention paid to public health. The
      importance of public health was slowly recognised over the period from 1970 to
      2000 with the publication of several reports from different organisations. The
      first authoritative policy statement that the important determinants of health
      lay outside health care was in the Lalonde Report from Canada. These ideas were
      subsequently expressed in the WHO Alma-Ata declaration and were emphasised a year
      later by the US Surgeon General. The idea of setting goals for health improvement
      also began in the 1970s. The Lalonde Report and the United Kingdom Black Report
      recommended that targets be used, but the first explicitly stated health targets
      were set by the US in 1979. WHO also identified the need for such targets at this
      time, but did not introduce them until 1984. Since then health targets have
      become a central feature of public health policy in developed countries. The
      Ottawa Conference on Health Promotion in 1986 championed the view that health
      promotion was central to achieving health goals internationally. It helped
      clarify the types of actions needed: that individuals need to be provided with
      the supportive environment and economic resources to be able to lead healthy
      lives. In a further development, the Healthy Cities Project was launched with the
      specific aim of involving political decision-makers in building a strong lobby
      for public health at the local level. The Healthy Cities Project illustrates how
      to provide means and opportunity for interventions to be implemented in
      communities. Concerns with inequalities in health were emphasised in the WHO
      declaration of Alma-Ata, and were the focus of the United Kingdom Black Report.
      The Jakarta Conference on Health Promotion in 1997 urged international action on
      poverty, as it is the major threat to health. International acceptance of the
      need to tackle inequalities took longer than the acceptance of health targets,
      but it is now an important feature of public health policy. The advent of the
      21st century marked the coming of age of public health. The renewed version of
      'Health for All', 'Health for All in the 21st Century', emphasised the one
      constant goal of WHO that all individuals should achieve their full health
      potential. Public health is now regarded internationally as being a priority with
      this WHO goal being adopted as the overarching goal of policy. The challenges it
      faces in tackling problems such as obesity, inequalities in health, smoking,
      alcohol and substance abuse are great and will require policies which tackle the
      economic, social and environmental determinants of health.

PMID- 16562776
TI  - Associations between xerostomia and health status indicators in the elderly.
AB  - AIMS: This study investigated the associations between xerostomia (dry mouth)
      (low, moderate and high) with other categorical variables (e.g. demographic and
      health status indicators). This paper aims to report on the severity of
      xerostomia in the elderly population and investigate the relationship with other
      aspects of perceived health. METHOD: Data were obtained from a cross-sectional
      survey of 225 elderly people from a large multilevel geriatric care centre. The
      centre consists of three levels of care: an apartment building in which residents
      live more or less independently, a home for the aged, and a chronic care
      hospital. Participants in the study were recruited when they attended the dental
      care facility. Data were collected by means of a personal interview conducted
      either at the dental care facility or the participant's residence. RESULTS: The
      mean age was 83 years. Most were females (72%) and almost all (99%) reported one
      or more chronic medical conditions; 88% had physical disabilities. Xerostomia was
      recorded on a seven-point scale. Scores were categorised as low, medium or high
      and the proportions were 49.3%, 30.3% and 20.4% respectively Bivariate analysis
      showed no association between dry mouth and sex, age, general health change or
      life satisfaction. However, when the high xerostomia group was separated out and
      odds ratios calculated they were 2.3 to 4.9 times more likely to experience a
      negative impact on health than the low group. Xerostomia did not have a
      significant impact on chewing capacity, morale or stress, although it contributed
      to the variability of the oral health-related quality of life measures. It was
      the only variable with a significant effect (OR 2.55) for the Oral Health Impact
      Profile-14 and displayed a higher odds ratio (2.76) for the Geriatric Oral Health
      Assessment Index. Self-reported xerostomia in the elderly population can be
      categorised into a severity scale. Those suffering most from xerostomia are more
      likely to experience a negative impact on general health. CONCLUSION: The key
      finding in this study is that xerostomia has a significant and negative impact on
      the quality of life of elderly individuals, though oral function may be less
      affected.

PMID- 16562777
TI  - A staged screening strategy for prenatal alcohol exposure and maternal risk
      stratification.
AB  - AIMS: To present an incremental process for a staged screening strategy to
      identify women at increased risk of having a child with fetal alcohol spectrum
      disorder (FASD) and to enhance the management of women using alcohol during
      pregnancy. We include an illustrative example of the development of a screening
      component using an existing data set. METHODS: We describe a seven-step protocol
      to screen for alcohol use during pregnancy. The screening process begins with a
      one-question initial screen, followed by exposure assessment, maternal risk
      stratification to estimate risk for FASD, and concludes with recommendations for
      intervention and monitoring of exposure for women drinking during pregnancy.
      CONCLUSIONS: This screening process has very modest time commitments in the early
      stages. Time commitments increase for women drinking during pregnancy and the
      process focuses on the population at highest risk of having a child with FASD.
      The process has the benefit of risk specificity, since the process refines risk
      estimates for an adverse outcome specific for FASD. The process concludes with a
      programme to facilitate intervention and to monitor changes in prenatal alcohol
      exposure during pregnancy. Prevention of FASD is an important public health
      priority. In addition to the ongoing study of clinical strategies to improve
      detection rates of alcohol exposure at all stages of pregnancy, additional
      research on the tools and the process used in screening efforts is urgently
      needed. The efforts should also include research on both the screening tools and
      the outcome of the screening process in routine prenatal care settings.

PMID- 16562778
TI  - Acute and long-term neurologic complications in children with acute lymphoblastic
      leukemia.
AB  - We reviewed the pattern of acute and long-term (during and after treatment
      period) neurologic complications in children with acute lymphoblastic leukemia
      (ALL). Among 265 patients, 40 developed neurotoxicity. Twenty-one and 19 of the
      patients were treated with St. Jude Total XI and St. Jude Total XIII chemotherapy
      protocols, respectively. There was no difference between Total XI and XIII
      chemotherapy protocol groups in neurotoxicity. Neurological symptoms were
      determined during the therapy period in 33 (82.5%) and in the late period in 7
      (15%) of 40 patients. Systemic chemotherapy (including vincristine, high-dose
      methotrexate) and intrathecal chemotherapy seem to be the most common
      predisposing factors. In the study group, neurological complications in two
      patients were iatrogenic as a result of lumbar puncture (1 case) and due to
      erroneous vincristine administration on two consecutive days (1 case).

PMID- 16562779
TI  - Childhood mediastinal masses in infants and children.
AB  - We reviewed all cases of primary pediatric mediastinal masses diagnosed and
      treated over a 24-year period. In this study, out of 187 primary mediastinal mass
      cases diagnosed between 1980 and 2004 in Istanbul University Istanbul Faculty of
      Medicine, Cardiovascular Surgery Department, 37 pediatric primary mediastinal
      mass cases were retrospectively evaluated according to age, sex, symptoms,
      diagnostic procedure, anatomical location, surgical treatment, histopathological
      evaluation and postoperative adjuvant therapy. The patients ranged in age from 2
      months to 15 years at the time of diagnosis, with a mean age of 8 years. There
      were 24 benign (64.8%) and 13 malignant (35.2%) tumors. The cases were lymphoma
      (27%), neurogenic tumors (21.6%), cystic lesions (18.9%), germ cell tumors
      (13.5%), thymic lesions (10.8%) and cardiac tumors (8.1%). Complete and partial
      resections of the tumor were the surgical procedures performed in 24 patients
      (64.8%) and 3 patients (8.1%), respectively. The three patients with a malignant
      tumor, in whom the entire mass could not be removed, received chemotherapy and
      radiation after surgery. In 10 patients with lymphoma, surgery was not a part of
      treatment and they received medical and radiation therapy after the establishment
      of the definitive diagnosis. All patients survived and were discharged from the
      hospital. Except for the cases with lyphoma, all patients are now free of
      recurrent disease. Compared to adults, children had more lymphomas and neurogenic
      tumors. Primary pediatric mediastinal malignancies are relatively common in
      infants and children. Lymphoma, neurogenic tumors and cystic lesions
      predominated. These differences between the age groups should also be considered
      when dealing with a mediastinal mass.

PMID- 16562780
TI  - Neonatal nosocomial sepsis in a level-III NICU: evaluation of the causative
      agents and antimicrobial susceptibilities.
AB  - Despite advances in supportive care and use of antibiotics, sepsis preserves its
      importance due to its high mortality and morbidity for neonates. Identifying the
      causative agents and antibiotic resistance yearly in a neonatal intensive care
      unit (NICU) helps the physician to choose the most appropriate empirical therapy.
      In this study we aimed to evaluate positive blood cultures and antibiotic
      susceptibilities of newborns with proven sepsis during the years 2000-2002 in our
      NICU. The charts of babies with sepsis were evaluated for clinical
      characteristics, positive cultures and antimicrobial susceptibilities,
      retrospectively. Although most of the admitted patients were premature (76.5%),
      the frequency of proven sepsis was quite low, at 9.1% among 909 newborns.
      Mortality rate in sepsis was 16%. The most commonly isolated micro-organisms were
      coagulase-negative staphylococci (CoNS) (31.3%), fungi (19.2%), Staphylococcus
      aureus (13%) and Klebsiella pneumoniae (10.5%). Methicillin resistance for CoNS
      was 92.3% and for S. aureus was 72.7%. In the last year, a significant increase
      in the frequency of Klebsiella pneumoniae (8.3 vs 14.2%), CoNS (27.1 vs 37.1%),
      Pseudomonas aeruginosa (2.1 vs 8.6%) and fungal infections (18.8 vs 20%) was
      observed compared to the previous years. An initial empirical antibiotic therapy
      for late-onset sepsis was designed with teicoplanin + piperacillin
      tazobactam/meropenem + antifungal (fluconazole or amphotericin B) as the best
      combination to cover this spectrum until the culture results arrive. However,
      this combination is only compatible with our results and may not be applied in
      all units. Every unit must follow the bacterial spectrum and antibacterial
      resistance patterns to choose their specific empirical treatment strategy for
      nosocomial infections.

PMID- 16562781
TI  - Serum immunoglobulin (IgG, IgM, IgA) and IgG subclass concentrations in healthy
      children: a study using nephelometric technique.
AB  - Immunoglobulin (Ig) G, IgM, IgA and IgG subclass (IgG1, IgG2, IgG3, IgG4)
      concentrations were determined in more than 500 healthy Turkish children using
      nephelometric technique. These parameters were thought to be highly varied for
      different ethnic groups because of environmental and genetic factors. Methodology
      used in previous studies has been reported to affect age-related normal values.
      Serum IgG, IgM, IgA and IgG1, IgG2, IgG3, IgG4 levels were measured in 510, 491,
      486, 542, 511, 515, and 545 healthy children, respectively. According to their
      age, the patients were divided into 14 groups. In contrast to most of the
      previous studies, age-related normal values for IgG4 levels were also obtained.
      In conclusion, it has been suggested that our study as an example for Caucasians
      using nephelometric technique will supply useful information about age-related
      normal serum immunoglobulin and IgG subclass concentrations.

PMID- 16562782
TI  - Vigabatrin in pediatric patients with refractory epilepsy.
AB  - New generation antiepileptic medications have improved seizure outcome in
      patients with intractable epilepsy. We studied the efficacy and side effect
      profile of vigabatrin (VGB) in pediatric patients with intractable seizure
      disorder. We reviewed the database of our short-term video-EEG monitoring
      laboratory to screen patients with intractable epilepsy who were on VGB either
      alone or in combination for three months or more. We subsequently reviewed the
      medical records of these patients to abstract clinical information regarding age,
      sex, seizure type, epilepsy syndrome, efficacy and side effects of VGB. Of 111
      patients, 75 (68%) were male and 36 (32%) female. Seizure onset was during the
      newborn period in 12 patients (11%), during the first year of life beyond the
      newborn period in 47 patients (42%), between 1-5 years in 23 patients (21%), and
      above five years in the remaining 29 patients (26%). Fifty-four patients (48.6%)
      had partial onset seizures with or without secondary generalization; 49 patients
      (44.1%) had primary generalized seizures; 8 patients (7.2%) had two or more types
      of seizure. Fifty-three percent of patients had mental retardation, and 35% had
      abnormal findings on physical/ neurological examination. Of 98 patients, 70
      (71.4%) had abnormal magnetic resonance imaging (MRI) findings. Ninety-seven
      percent of patients had been on polytherapy before VGB was added to treatment.
      VGB reduced seizure frequency by at least 50% in 33.3% of patients with partial
      seizures, and in 30.6% of patients with primary generalized seizures. Six of the
      responders with partial seizures had complete resolution of their seizures. Most
      common side effects included visual field defects, increased appetite and
      obesity. Vigabatrin seems to be more effective in partial seizures in childhood
      intractable epilepsy. Patients should be closely monitored regarding side effects
      of VGB.

PMID- 16562783
TI  - Diagnostic criteria of pediatric migraine without aura.
AB  - The objectives of this study were to assess the validity of the International
      Classification of Headache Disorders-I (ICHD-I) and the International Headache
      Society-Revised (IHS-R) criteria and to evaluate the other headache features that
      are not included in these criteria for migraine without aura in the pediatric
      population. One hundred and thirty-two children who referred to our clinic with
      the complaint of chronic or recurrent headache were evaluated. Clinical diagnosis
      of the pediatric neurologist was used as the gold standard in evaluating the
      validity of ICHD-I and IHS-R criteria and the other headache features. After
      eliminating patients with other migraine types, secondary headache, and missing
      data, 92 patients were included in the study according to their records. Sixty
      one children (66.3%) were diagnosed as migraine without aura. Using the clinical
      diagnosis as the gold standard, the specificity of ICHD-I criteria was detected
      as 93.5%, while the sensitivity was detected as 36.1%. IHS-R criteria had 90.3%
      specificity and 78.7% sensitivity. Relief of headache with sleeping or lying down
      in a dark, quiet room was found to be the highest specific and sensitive factor
      of the other headache features not included in these criteria. IHS-R criteria
      were found to be more valid in the diagnosis of migraine without aura than ICHD-I
      criteria. IHS-R criteria are recommended both in clinical practice and in the
      studies requiring migraine without aura case definitions in the pediatric
      population.

PMID- 16562784
TI  - Erythema nodosum in childhood: evaluation of ten patients.
AB  - Erythema nodosum (EN), which is a rare skin manifestation among children, is
      precipitated by a range of infectious and non-infectious diseases. The purpose of
      this study was to evaluate the epidemiology, etiology, clinical manifestations
      and course of EN among children. A total of 10 patients diagnosed with EN between
      January 2000 and March 2004 at Hacettepe University Ihsan Dogramaci Children's
      Hospital, Pediatric Infectious Diseases Outpatient Clinic, were studied
      retrospectively. The study population consisted of five girls and five boys, with
      a mean age of 8.8 +/- 3.3 years (range, 4-14 years). In five of the 10 children
      (50%), the etiology of EN was established: three had streptococcal infection and
      two were diagnosed as primary tuberculosis; the etiology of EN could not be
      determined in 50% of the cases. The duration of the recovery of lesions varied
      from 4 to 12 days (mean, 8.2 +/- 2.6 days). Our data confirm the predominance of
      streptococcal infections among the etiologic factors while also considering
      tuberculosis as a causative factor among children with EN in Turkey.

PMID- 16562785
TI  - The effect of childhood obesity on respiratory function tests and airway
      hyperresponsiveness.
AB  - The aims of this study were to investigate the effect of exogenous obesity on
      respiratory function tests, to define the relationship between the severity of
      obesity and respiratory function test parameters, and to detect the incidence of
      airway hyperresponsiveness and exercise-induced bronchospasm in an obese study
      group. This cross-sectional controlled study was done with 38 exogenous obese
      patients, aged 9 to 15 years, and 30 healthy children. Basal respiratory function
      test parameters were measured with spirometry. To display airway
      hyperresponsiveness, 4.5% hypertonic saline provocation test was used; exercise
      induced bronchospasm incidence was defined with bicycle ergometry. Basal
      respiratory function test parameters were lower in the study group as compared
      with the control group. Exercise test was positive in 31.6% of the obese group
      and in 3.3% of the control group (P = 0.003). The provocation test with
      hypertonic saline test was positive in 18.4% of the obese group. There were
      strong negative correlations between body mass index (BMI), relative weight, skin
      fold thickness, waist/hip circumference ratio and basal forced vital capacity
      (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow
      (PEF) values. The diagnosis and management of exercise-induced bronchospasm may
      improve exercise performance and physical activity, assist with weight loss, and
      break the vicious circle.

PMID- 16562786
TI  - Urinary tract infection and hyperbilirubinemia.
AB  - The aim of this study was to evaluate the incidence of urinary tract infection
      (UTI) in newborns with asymptomatic, unexplained indirect hyperbilirubinemia in
      the first two weeks of life. Jaundiced infants, otherwise clinically well, less
      than two weeks of ages, with a total bilirubin level above 15 mg/dl were eligible
      for the study. A bilirubin work-up including glucose-6-phosphate dehydrogenase (G
      6 PD) level, as well as urinalysis and a urine culture were performed in all
      patients. Patients with UTI, defined as more than 10,000 colony-forming units per
      milliliter of a single pathogen obtained by bladder catheterization, were
      evaluated for sepsis. Renal function tests and renal ultrasound were performed in
      cases with UTI. During follow-up, voiding cystourethrogram (VCUG) and
      dimercaptosuccinic acid scintigraphy (DMSA) were performed as well. A total of
      102 patients were enrolled. The bilirubin work-up of patients did not demonstrate
      any significant underlying disorder. None of the infants had a high direct
      bilirubin level. UTI was diagnosed in eight (8%) cases [Enterobacter aerogenes
      (3/8:38%), Enterococcus faecalis (2/8:25%), Klebsiella pneumoniae (2/8:25%) and
      Escherichia coli (1/8:12%)]. Of those eight patients, only four (50%) had pyuria.
      Bacteriuria was present in seven (88%) patients. The sepsis screen was negative
      in all but one case with a high C-reactive protein (CRP) level. None of the
      patients had a positive blood culture. Renal function tests were within normal
      levels in all patients. Renal ultrasound showed urinary tract abnormalities in
      three (38%) patients (hydronephrosis, n=1 and pelviectasis, n=2). VCUG was
      performed in all patients during the study period and one had unilateral grade 3
      4 reflux, while only one patient had a diverticulum of the bladder. DMSA was
      performed in seven patients and none had renal scars. It is of importance that
      UTI can occur in asymptomatic, jaundiced infants even in the first week of life.
      Although it is well known that UTI is a common cause of prolonged jaundice, urine
      culture should be considered in the bilirubin work-up of infants older than three
      days of age with an unknown etiology.

PMID- 16562787
TI  - Determination of the risks of domestic accidents for the 0-6 age group in the
      Tuzlucayir Village Clinic neighborhood.
AB  - This study was planned and conducted based on the investigation of families
      living in the Tuzlucaylr Village Clinic neighborhood to determine the risks of
      domestic accidents for the children aged 0-6 years. It was established that 66.0%
      of the rooms were furnished with sharp-edged furniture; 63.2% had open electrical
      sockets; 68.4% had slippery flooring; and 68.9% of the houses with balcony
      railings had rail openings wide enough for a child to pass through. We determined
      that 28.8% of the children aged 0-6 years had suffered a domestic accident during
      the last year.

PMID- 16562788
TI  - A rare cause of anemia and thrombocytopenia in a newborn: congenital malaria.
AB  - A newborn with fever and jaundice was referred to our hospital with anemia and
      thrombocytopenia of unknown origin. The patient's mother suffered from malaria
      infection during the third trimester of her pregnancy, but she did not accept
      medical therapy. On physical examination the newborn showed mild splenomegaly and
      jaundice. Laboratory tests revealed marked anemia with a hemoglobin value of 7.7
      g/L and thrombocytopenia with platelet numbers of 17,000/mm3. Plasmodium vivax
      was detected in blood smear. Oral therapy with chloroquine and primaquine was
      started. This patient is the second case of congenital malaria reported from
      Turkey, and shows that the diagnosis of congenital malaria should be considered
      in infants with suspected congenital infection who are born to mothers with a
      history of malarial disease. We emphasize the importance of adequate antenatal
      medical therapy during pregnancy.

PMID- 16562789
TI  - A case of Wiskott-Aldrich syndrome with de novo mutation at exon 4.
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by
      thrombocytopenia, eczema and immunodeficiency. Clinical features of the disease
      are highly varied; therefore, the diagnosis is sometimes difficult, especially in
      solitary cases or cases with milder forms of the disease. However, the
      identification of the WASP gene has made possible a definite WAS diagnosis for
      these cases. In this report, we present a 26-month-old boy who had received
      several ineffective treatments for chronic immune thrombocytopenic purpura. He
      was then suspected to have WAS because of the early onset of thrombocytopenia and
      small platelets. The diagnosis became definite with the detection of a de novo
      mutation at exon 4 of the WASP gene, Arg138Pro, through mutation analysis.

PMID- 16562790
TI  - Peritoneal tuberculosis with elevated serum CA 125 level mimicking advanced
      ovarian carcinoma in an adolescent.
AB  - Differential diagnosis between tuberculous peritonitis and peritonitis
      carcinomatosis is extremely difficult in patients with ascites, peritoneal
      implants and elevated CA 125 level. A 16-year-old girl presented with abdominal
      distention, intermittent fever and weight loss. Physical examination and
      radiologic studies revealed massive ascites, generalized peritoneal thickening
      and slightly enlarged right ovary with a cystic mass and left pleural effusion.
      Serum CA 125 was 939 U/L (normal range: 0-35 U/L) and other tumor markers
      including alpha fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG)
      were within normal range. Acid-fast stain and culture were negative for
      Mycobacterium tuberculosis. Diagnostic laparoscopy and biopsy were performed with
      the presumptive diagnosis of peritonitis carcinomatosis, and histologic
      examination revealed multiple granulomas with epithelioid cells and caseification
      necrosis which confirmed tuberculosis. Quadruple anti-tuberculosis treatment was
      administered and the patient's clinical findings and serum CA 125 level returned
      to normal. In conclusion, tuberculous peritonitis should be considered in the
      differential diagnosis of patients with ascites and elevated serum CA 125. This
      marker may be useful in monitoring treatment response.

PMID- 16562791
TI  - Fatal course of ABO hemolytic disease associated with hydrops in a twin
      pregnancy.
AB  - Hydrops fetalis associated with ABO incompatibility is an extremely rare
      condition. We report twin infants both afflicted with significant ABO hemolytic
      disease but showing different degrees of clinical severity, in which fatal
      hydrops developed in one of the twins. Hemolysis due to ABO incompatibility is
      usually difficult to diagnose. All causes of non-immune hydrops should be ruled
      out in order to identify hydrops due to ABO incompatibility.

PMID- 16562792
TI  - Cardiac echinococcosis with intra-atrial localization.
AB  - Echinococcosis is a frequently encountered parasitic disease in the Mediterranean
      region, including Turkey. Cardiac disease is seen in 0.5-2% of patients. Usually
      the cysts are located within the pericardium or intramyocardially; intracavitary
      localization of the cyst is rarely seen. We herein report a patient who initially
      presented with hemoptysis and was echocardiographically diagnosed to have an
      intra-atrial hydatid cyst. Although patients with cardiac hydatid cysts may
      present with cardiac symptoms, symptoms typically involve other organ systems,
      following dissemination of the organism. Therefore, echocardiographic screening
      of patients who are diagnosed with echinococcosis, even if they have no cardiac
      symptoms, may ensure early diagnosis and prevent development of lethal
      complications, such as cyst rupture or embolization.

PMID- 16562793
TI  - Phagophobia: a case report.
AB  - Phagophobia is a form of psychogenic dysphagia. Although it is characterized by a
      fear and avoidance of swallowing food, fluids, or pills, physical examination and
      laboratory findings are normal. Here, we present a case of phagophobia, who at 13
      years of age was brought to our hospital by his family because of his fear and
      avoidance of swallowing food and loss of weight. After psychiatric interview, the
      patient underwent an oral peripheral examination, stroboscopic laryngeal
      evaluation, the Bedside Swallow Evaluation, and the Modified Barium Swallow
      Study. His physical examination and all laboratory findings were normal. The
      management of this case included the combination of behavior therapy and a
      dysphagia management program. After approximately one month of utilizing these
      techniques, the case showed considerable improvement.

PMID- 16562794
TI  - Fire-eater's pneumonia after aspiration of liquid paraffin.
AB  - Fire-eater's pneumonia is a distinct type of chemical pneumonitis that results
      from aspiration of different types of hydrocarbons. This article describes a case
      of fire-eater's pneumonia due to accidental aspiration of liquid paraffin. The
      adolescent patient became febrile the day after the accident. The diagnosis of
      fire-eater's pneumonia was delayed because aspiration history was not divulged by
      the patient from the beginning. The most prominent chest X-ray finding was
      multiple pneumatoceles. He responded well to antibiotics and corticosteroids. Two
      months after the accident, the lesions had almost completely resolved and only
      minor scarring was evident. Diagnosis of fire-eater's pneumonia can be difficult,
      especially if key aspects of related history are not divulged by the patient.
      Corticosteroid therapy was thought to be beneficial in the rapid recovery of the
      present case together with broad spectrum antibiotics.

PMID- 16562795
TI  - Fatal giant pediatric intracranial cavernous angioma.
AB  - Cavernous angioma is a benign vascular lesion that may occur in the central
      nervous system. The symptoms of raised intracranial pressure or consciousness
      alteration are usually related to acute hemorrhage. A previously healthy four
      year-old girl was admitted with sudden loss of consciousness, vomiting and clonic
      seizures. Her Glasgow coma score (GCS) was 7 at presentation (5 m 1v 1e).
      Anisocoria and mydriasis were present on the right. Computerized tomography
      revealed a giant spherical, hyperdense intraaxial left frontoparietal lesion. The
      findings of surrounding vasogenic edema and compression of the adjacent lateral
      ventricle were seen on computerized tomography (CT). She was taken to operation
      and the mass was grossly excised. The GCS remained unchanged. A diagnosis of
      brain death was made. A cavernous hemangioma was diagnosed with pathologic
      examination. In conclusion, a cavernous angioma may occasionally follow a rapid
      and fatal course by causing gross hemorrhage in the pediatric age group. Early
      recognition by CT or magnetic resonance imaging (MRI) and prompt surgical
      evacuation are necessary.

PMID- 16562796
TI  - A rare cause of respiratory distress in infants: tracheal compression due to
      anomalous course of innominate artery.
AB  - Incomplete vascular ring is a rare congenital vascular anomaly causing tracheal
      compression. A case of anomalous innominate artery causing tracheal compression
      and low grade tracheomalacia with remarkable dyspnea and intermittent apnea in a
      five-month-old infant is reported. Chest X-ray revealed enlarged upper
      mediastinum. Patent foramen ovale and thymus hyperplasia were detected on
      echocardiographic examination. Angiography demonstrated left aortic arch with
      normal arterial branching pattern. Thorax computerized tomography (CT) revealed
      tracheal compression of more than 50% at innominate artery level and aberrant
      position of the hyperplastic thymus. Operation was planned for subtotal
      thymectomy and relocation of innominate artery in order to relieve tracheal
      obstruction. Postoperative thorax CT demonstrated satisfactory relief of tracheal
      compression. Patient was discharged from hospital on sixth postoperative day in
      good condition. On clinical follow-up he is completely asymptomatic without any
      signs of dyspnea or intermittent reflex apnea. In severely symptomatic cases,
      surgical treatment offers excellent results.

PMID- 16562797
TI  - A very rare case of polysplenia syndrome with congenital diffuse pulmonary
      arteriovenous fistulas.
AB  - A five-year-old girl patient was admitted with cyanosis and dyspnea, which
      started from birth. She had small telangiectatic lesions on her face and cerebral
      arteriovenous malformation, but no family history of hereditary hemorrhagic
      telangiectasia. Contrast echocardiography and pulmonary angiography demonstrated
      diffuse pulmonary arteriovenous fistulas. The patient was diagnosed as
      polysplenia syndrome characterized with left atrial isomerism, interrupted
      inferior vena cava, azygous continuation to the superior vena cava, and hepatic
      veins draining to the right atrium. In contrast to the other polysplenia syndrome
      cases, in this patient, pulmonary arteriovenous fistulas were not associated with
      cavopulmonary anastomoses or liver disease.

PMID- 16562799
TI  - The road to population health: using Healthy People 2010 in nursing education.
AB  - Healthy People 2010: Understanding and Improving Health and corresponding state
      health improvement plans provide roadmaps for planning, monitoring, and
      evaluating population health improvement in the United States. These documents
      offer relevant guidance for nursing education because they address health
      workforce education specifically, use a population perspective, and include
      evidence-based action priorities. However, information about how these documents
      are used in nursing education is limited. This article discusses the relevance of
      national and state health planning documents for nursing education. Nurse
      educators are encouraged to reflect on the alignment of current nursing education
      efforts with national and state health planning agendas. Suggestions for future
      use of national and state population health improvement planning documents in
      guiding strategic, curricular, and course planning are offered.

PMID- 16562800
TI  - Teaching quality improvement in the classroom and clinic: getting it wrong and
      getting it right.
AB  - The world in which today's graduates will provide care is changing, as are
      expectations about caregivers' performance. Learning how to improve quality of
      care must occur during, and as part of, learning about patient care. In this
      article, I describe a continuous quality improvement learning program that was
      integrated into nursing students' education and a study evaluating the students'
      experiences with the implementation of the program through open-ended questions
      and focus groups. The program consisted of three parts: participating in a
      personal improvement project; observing and describing a patient process from the
      patient's perspective; and working in teams with process improvement in clinical
      practice. The findings indicated the students learned improvement methods and
      tools during their personal improvement projects, but their ability to translate
      that knowledge into action, and thereby improve patient care, was insufficiently
      developed through coaching, reflection, and role modeling. In other words, the
      experience was not integrated into the students' general education. In addition,
      faculty and clinical staff did not seem to be adequately informed and had limited
      knowledge of the students' clinical improvement projects.

PMID- 16562801
TI  - Complementary and alternative therapies: a new frontier for nursing education?
AB  - The field of complementary and alternative medicine (CAM) is relatively new to
      Western health care and scientific research. The American public is embracing the
      use of CAM, and consequently, health care professionals will have to integrate
      these therapies into their professional practice. With the addition of basic CAM
      components to the newest NCLEX-RN blueprint, nursing education programs at all
      levels must incorporate CAM into their curricula. There are challenges to be
      faced with the implementation of added content, but nurse educators have
      successfully faced these challenges in the past. Specific strategies for
      integrating CAM topics into nursing curricula are discussed.

PMID- 16562802
TI  - Faculty members' perceptions of medical genetics and its integration into nurse
      practitioner curricula.
AB  - This study assessed faculty members' perceived knowledge of medical genetics
      concepts and conditions, the importance of integrating this content into NP
      curricula and how this was being done. During a national NP conference, 40 NP
      faculty voluntarily completed surveys. Participants' perceived knowledge of
      genetics varied; 35% noted low or very low knowledge, and only 5% reported high
      or very high knowledge. Most participants (95%) believed genetics is important,
      but only 10% reported having separate genetics courses in their NP programs.
      Approximately half of the participants reported personal involvement in genetics
      NP education, and 50% reported barriers to implementing it into their curricula.
      Most faculty indicated they did not feel comfortable teaching genetics, nor did
      they have formal training in the area. Advancing medical genetics into NP
      curricula will require ongoing faculty development and training to sustain and
      build genetics skills and competencies for advanced practice nurses.

PMID- 16562803
TI  - Preparing nursing students to be health educators: personal knowing through
      performance and feedback workshops.
AB  - Newly graduated RNs are expected to be competent health educators for
      individuals, groups, and communities. To prepare for this complex role, nursing
      students need time to focus on developing basic teaching skills and self
      confidence in a non-threatening learning environment. Of primary importance to
      novice teachers' development is taking the time to identify and appreciate the
      personal dimensions that are an integral part of the health educator role. Carper
      identified personal knowing as one of the four ways of knowing in nursing. This
      article describes an innovative praxis strategy that used videotaped
      performances, learner feedback, and self-reflection to encourage personal knowing
      in relation to the experience of nursing students learning to teach groups of
      clients.

PMID- 16562804
TI  - Comparing the frequency of physical examination techniques performed by associate
      and baccalaureate degree prepared nurses in clinical practice: does education
      make a difference?
AB  - Rapid changes in health care have underscored the need for reform in health
      professions education, including nursing education. One of many problems cited in
      the nursing and other health sciences education literature is overcrowded
      curricula; therefore, an evaluation of content is necessary. The purpose of this
      study was to determine whether differences exist in the frequency that physical
      examination techniques are performed by associate and baccalaureate degree
      prepared nurses. Participants completed a survey on performance of various
      physical examination techniques. A Mann-Whitney test showed no differences
      between the two groups in terms of frequency of techniques performed. A small
      negative correlation was found between frequency and years of experience with the
      nutrition assessment category. A comparison of physical examination content
      covered in baccalaureate and associate degree nursing programs is needed to
      further understand these findings.

PMID- 16562805
TI  - Students' and faculty members' knowledge and attitudes regarding pain management:
      a descriptive survey.
AB  - Many basic nursing programs spend little time educating students about pain
      management. Between the years of 2000 and 2002, a baccalaureate nursing program
      at a university in central Virginia surveyed sophomore, junior, and senior
      nursing students using McCaffery's Pain Knowledge and Attitude Survey at the
      beginning and end of each academic semester. During the same time period, faculty
      also completed the survey and answered open-ended questions pertaining to the
      inclusion of pain management in course content. The purposes of this study were
      to determine the baseline knowledge and attitudes of nursing students and faculty
      about the science of pain management and to evaluate the content of pain
      management material and the extent to which it is integrated into the curriculum.

PMID- 16562806
TI  - [Dietary behavior disorders: opinions and expectancies on prevention and
      treatment strategies from the perspective of the several social actors].
AB  - AIMS: The prevalence increase of Eating Disorders in the last decades emphasizes
      the necessity to develop strategies from the public healthcare system which
      include the perspective of the principal implicated social actors. The present
      study aims to know their opinions and expectations regarding the prevention and
      treatment of Eating Disorders. METHODS: Realization of 5 focus groups (with
      relatives, adolescents, professionals from the health and educational sector,
      representatives from institutions and support groups) and 14 semi-structured
      interviews (with Eating Disorder patients and relatives) about strengths and
      weaknesses of actual prevention and treatment programs, expectations of change
      and suggestions for improvement. Analysis of contents and triangulation of
      results. RESULTS: The absence of resources and knowledge about Eating Disorders,
      the scarcity of transversal programs and insufficient coordination were named as
      the main weaknesses whereas interdisciplinary pilot programs were positively
      valued. As principal demands, major endowment of human and material resources,
      increased coverage of specialized services, promotion of specific training and
      improvement of coordination was asked for. Regarding prevention, preference
      toward an unspecific approach to the subject in order to hinder imitation between
      young people was highlighted. The care in Day Hospitals was considered one of the
      most appropriate treatment modalities for the characteristics of this disease
      being valued the potentially therapeutic effect of contact between Eating
      Disorder patients. The support network, the education field and the family were
      named as other important pillars in a multidisciplinary approach to the disease.
      There was also a demand for the development of combined programs. CONCLUSIONS:
      The discussion of different psychotherapeutic approaches, the role of support
      groups in the caring network as well as the post-hospital follow-up were
      identified as issues open to future research.

PMID- 16562807
TI  - [Effects of parenteral glutamine in patients submitted to bone marrow
      transplantation].
AB  - Bone marrow transplantation (BMT) is a therapy used for hematologic malignancies
      and solid tumors. Associated chemotherapy and radiotherapy to which these
      patients are submitted induce secondary effects, with a high metabolic stress.
      Glutamine is considered a conditionally essential amino acid, and has been shown
      effective in severe catabolic states. The aim of the study was to assess the
      effect of parenteral nutrition (PN) therapy supplemented with glutamine on
      duration of nutritional support in a group of patients with BMT. We have also
      analyzed associated complications, the nutritional status, the clinical course at
      6 months, differences as to type of transplantation, and oral ingestion
      capability. This is a phase IV, randomized, double blind, and parallel clinical
      trial, done at a single center. The study was performed on 49 patients, 29% male
      and 71% female patients, with ages between 21-63 years, distributed in 3
      diagnostic groups (leukemia, lymphoma, and solid tumors), and admitted to the
      Hematology Department of our Hospital. Fifty percent of the patients in each
      group have received PN supplemented with glutamine (0.4 g/kg/day of L-alanine-L
      glutamine), and the other 50% have received standard PN. RESULTS: we have not
      found significant differences nor at the beginning nor at the end of the study
      between both groups with regards to studied variables. CONCLUSIONS: PN is and
      effective therapy for maintenance of the nutritional status in patients submitted
      to a therapy with a, highly catabolic effect such as BMT. Although we have not
      been able to show the efficacy of glutamine supplementation in this study with
      the used dose, it does have been effective in other reports.

PMID- 16562808
TI  - [Malnutrition of home-based hospital patients].
AB  - OBJECTIVE: We pretend to know the nutritional state in all patients that are
      being treated in the the Home Care Services Hospital Based (HCSHB) units, be
      which is their entrance causes and we also pretend to know the prevalence of
      undernutrition. SECONDARY OBJECTIVE: To know the prevalence of nutritional
      treatments in the HCSHB units, their relationship with the nutritional state, the
      pathology and the patient's origin inside the sanitary environment. ENVIRONMENT:
      A Multicentric study, in which the HCSHB units of three hospitals of the Valencia
      Community have intervened. PATIENT: 40 patients that remained in that moment
      entered by different causes in the HCSHB units. VARIABLES: Sex, age. Origin
      service, pathology, Subjective Global Valuation (SGV), IMC, nutritional support,
      type of nutritional support, albumin, Cholesterol, lymphocytes. RESULTS: The half
      age has been of 77,45 years (SD 11 years) with 67,5% of males. The patients, in
      all the cases, came from hospital Services, being the pathology responsible for
      the entrance mainly the oncological 32,5%, surgical 7,5%, neurological 7,5% and
      52,5% others. According to GSV 52.5% present a good nutritional status, 37.5% had
      a suspect of under nourishment and 10% had a clear under nourishment. The IBM for
      the 12.5% of the patients is < or = 20 and the IBM for the 42.5% < or = 22. The
      35% were receiving nutritional support, supplements the 78% and oral enteral
      nutrition the 14% of the patients. We have found a lineal relation between the
      IBM and the levels of albumin that the patients presented, also with the figures
      of cholesterol and it has not been found any relationship with the lymphocytes
      number.

PMID- 16562809
TI  - [Situation and adequacy analysis of dysphagia diets at a regional hospital].
AB  - The study aims at confirming the adequacy of diets prescribed for dysphagia
      during hospitalization through a specific questionnaire to identify, give advice,
      and manage dysphagia. To compare and analyze the diet for dysphagia offered at
      our Hospital with the recommendations for a dysphagia diet published in recent
      nutritional literature. From the results obtained, to establish diet improvements
      (if necessary) and nursing working tools aimed at early detection of swallowing
      problems and decreasing the risk for Hyponutrition, dehydration and aspiration.
      SUBJECTS AND METHODS: A cross-sectional study among patients from our hospital
      with a prescription for a dysphagia diet is performed, assessing the diet
      usefulness, the characteristics of the 30 patients admitted at the Hospital
      Complex of Segovia, in several nursing units and with an established diet for
      dysphagia for two months and with different pathologies. Ages were comprised
      between 68-85 years. RESULTS: The questionnaire was analyzed and we verified that
      all patients had a swallowing impairment. The nutritional analysis showed an
      inadequate adaptation of hospital diet to dysphagia patients with regards to
      consistency of some dishes and the poor energy intake was significant (x 1339
      kcal), poor protein intake (58 g), and a deficiency in some minerals (iron and
      calcium), and vitamins (vitamin C). CONCLUSIONS: Dysphagia is a problem that
      affects a considerable number of patients in our Hospital (10-15%). The diet
      provided by the Hospital was inadequate before the study. A more adequate diet
      has been designed with regards to nutritional value and consistency, its
      indication is broaden, as well as interventional measures and previous patient
      assessment. The Nutrition Unit has implemented improvements in nutritional
      content.

PMID- 16562810
TI  - [Comparative analysis of nutritional status, food intake and length of
      hospitalization considering two hospitals: public versus private].
AB  - INTRODUCTION: To assess the nutritional status of hospitalized patients is
      important for the prevention of hospital malnutrition and planning of nutritional
      intervention. OBJECTIVE: To comparatively analyze the nutritional status of
      patients admitted to two hospitals, one public and another private, caring for
      populations with different socioeconomic profiles. CASE STUDY AND METHODS: This
      was a prospective study and samples were collected from patients of two
      hospitals, one public (PUH) and another private (PRH), which respectively
      represent the underprivileged and the more affluent populations. The analysis
      considered 51 patients from the PUH, aged between 53.9 +/- 15.6 years and 51 from
      the PRH, aged between 55.0 +/- 13.9 years, paired and grouped according to the
      following diseases: neoplasia (n+25), digestive tract disorders (n+11) and others
      (n+15). The statistical analysis was made by means of the T-Student test to
      compare PUH and PRH variables with p < 0.05, as well as to compare different
      variables in the same hospital, with p < 0.05; p < 0.01; p < 0.005 and p < 0.001.
      RESULTS: There were no statistical differences when the variables evaluated in
      both hospitals were compared, except for the length of hospitalization of
      patients with digestive tract disorders, which was longer for HPR. Upon
      hospitalization, 21.0% and 17.6% presented a body mass index (BMI) indicative of
      malnutrition. The patients with neoplasias presented current weight (CW) lower
      than habitual weight (HW). Both the patients with neoplasias and those with
      digestive tract disorders presented insufficient energy consumption in the period
      before hospitalization (p < 0.05). A negative correlation was found between the
      length of hospitalization and the current weight/habitual weight ratio (r =
      0.194, 0 < 0.05, n = 102) and BMI (r=-0.186, p < 0.05, n = 102), according to
      Pearson's coefficient. CONCLUSION: The similarity of nutritional conditions found
      points to similarity of nutritional status for patients of both institutions and
      reflects the changes in the nutritional status of the population. The nutritional
      intervention should consider the nutritional needs of the population assisted.

PMID- 16562811
TI  - Characteristics of glucose transport across the microvillous membranes of human
      term placenta.
AB  - Transport characteristics of D-glucose were studied in the microvillous vesicles
      isolated from the human term placenta. Transport occurred by selective and rapid
      facilitated diffusion system which was inhibitable by phloretin and HgCl2. The
      transport was dependent on a transmembrane. Na+-gradient indicating a "secondary
      active transport" system operating. The transport influx was saturable and the
      kinetic analysis based on Hanes-Woolf plot produced a kt and Jmax value of 1.2 mM
      and 34 nmoles.mgprotein(-1).min(-1), respectively. The efflux of D-glucose from
      the membrane vesicles in a pre-equilibrated assay conditions showed a distinct
      biphasic pattern differing significantly in the half time efflux. The t1/2 of the
      fast and slow components was found to be 15 sec and 660 sec, respectively. The
      transport showed distinct sensitivity to temperature and the Ea values both below
      and above the transition temperature of 37 degrees C, as calculated from the
      Arrhenius plot were found to be 7600 and 5472 kCal.mol(-1), respectively.
      Inhibition studies with a number of sugars for hexose transport pathway showed
      that the glucose epimers, phosphorylated sugars, and even the disaccharides and
      the pentose sugars competed effectively with D-glucose. The influx was also
      inhibited by a number of steroids such as progesterone, 17alpha
      hydroxyprogesterone, testosterone and estrogen. Insulin was found to increase
      glucose transport in a dose- dependent fashion at a concentration of 0.2-1
      unit.ml(-1). Ouabain, dinitrophenol and nicotine strongly inhibited D-glucose
      uptake in the membrane vesicles.

PMID- 16562812
TI  - [Assessment of protein quality in foods by calculating the amino acids score
      corrected by digestibility].
AB  - The protein score reflects its amino acids (AA) content in comparison with the
      ideal protein. However, when there is a need to know the use of AA by the
      organism it is necessary to do a correction of the score value by protein
      digestibility (PDCAAS). Since this information is not available for usually
      consumed foods, the present work aimed at calculating the PDCAAS values of these
      foods. The score was calculated the limiting AA of 70 foods, taking as reference
      protein the AA pattern for children > 1 year old and adults proposed by the U.S.
      National Academy of Sciences for the year 2002. The PDCAAS value was obtained in
      each case by multiplying the score value by the digestibility index. For
      vegetable foods the obtained score values and PDCAAS were, respectively:
      vegetables 88.5% / 73.4%, tubercles 89.44% / 74.24%, fresh fruits 75.6% / 64.3%,
      dried fruits 65.6% / 48.1%, legumes in general 89.2% / 69.58%, chickpea and
      soybean 100% / 78%, cereals and derivatives 68.8% / 58.5%. Creation of table that
      contents the score values, digestibility values, and PDCAAS of foods is a useful
      tool when food selection for a dietary plan based on its protein quality is
      desirable.

PMID- 16562813
TI  - [Influence of the -866G/A polymorphism of the UCP2 gene on an obese pediatric
      population].
AB  - OBJECTIVE: In the present study, our objectives were to evaluate the prevalence
      of -866G/A mutation of UCP2 gene and to study its influence on the phenotype of
      obese children (11-12 years old) from Navarra. BACKGROUND AND STUDY SETTING:
      Obesity is a disease with a multifactorial origin that may related be to the
      presence of mutations and polymorphisms in several candidate genes. The gene of
      the uncoupling protein UCP2 is one of the most studied ones in relation to
      obesity because it seems to participate in body composition and several metabolic
      processes control. Three polymorphisms have been described for this gene: an
      insertion/deletion of 45 nucleotides, a nucleotide change of guanine for adenine
      in -866 position, an another change that replaces alanine for valine at amino
      acid position 55. According to several studies, the -866G allele is related to an
      increased risk of developing obesity, although the results are contradictory
      about this association in the literature. SUBJECTS: The study was carried out on
      125 obese children (52% male), aged 11-12 years, selected through the Pediatric
      Endocrinology Departments of Clinica Universitaria and Hospital Virgen del Camino
      of Pamplona (Spain), the reported results on this association are contradictory.
      INTERVENTIONS: After checking the inclusion criteria, anthropometrical data
      (weight, height, BMI, tricipital and subscapular skinfolds) were taken, and the
      percentage of fat mass was measured by bioelectrical impedance. Besides, plasma
      levels of total cholesterol, glucose, insulin, and leptin were measured. DNA was
      extracted from white blood cells to determine the genotype by PCR technique
      followed by BstUI digestion and further visualization in agarose gel with 2%
      ethidium bromide. RESULTS: The genetic analysis revealed a 0.404 frequency of the
      allele A, with a percentage of individuals G/G, G/A, and A/A of 40.0%, 39.2%, and
      20.8%, respectively. Carriers of the A allele had a significantly higher sum of
      tricipital and subscapular folds (p = 0.034). No significant differences between
      mutant and non-mutant subjects with regard to the studied biochemical variables
      were observed. CONCLUSIONS: Subjects carrying the polymorphism present higher
      values of tricipital and subscapular skinfolds as compared to non-mutant
      subjects, which may indicate a relationship between the presence of the A allele
      in obese children and higher amounts of subcutaneous fat.

PMID- 16562814
TI  - [Assessment of activity of care of a nutritional support multidisciplinary team
      in the follow-up of total parenteral nutrition].
AB  - INTRODUCTION: In total parenteral nutrition (TPN) nutritional support
      multidisciplinary teams (NSMT) must provide a high quality nutritional assistance
      based on evidence and daily follow-up of patients with TPN. OBJECTIVES: To assess
      the degree of adherence to quality standards of care provided to patients on TPN
      by the NSMT in two consecutive annual periods, according to structure, procedure,
      and outcomes indicators, previously defined in the team working protocol.
      PATIENTS AND METHODS: Prospective study of all patients that received TPN at our
      Center (421-bed general teaching hospital) during the years 2002 and 2003, using
      the data introduced in NUTRIDATA by daily follow-up of clinical and analytical
      conditions, and nutritional and non-nutritional complications, comparing both
      periods and considering an statistical significance level of p < 0.05. RESULTS:
      One hundred and sixty-three patients and 145 patients received TPN during 2002
      and 2003(65.9% male), respectively, with similar parameters of gender, age,
      indications for TPN, baseline nutritional status, mean nutritional supply, and
      non-nutritional complications. As to the different quality indicators established
      in the comparative study, we found a significant improvement in 2003 vs. 2002 in
      relation to initial anthropometrical assessment (71.03% vs 51.53%; p < 0.001),
      initial biochemical assessment (97.93% vs. 92.63%; p < 0.04), performance of
      systematic monitoring analysis (84.83% vs. 71.78%; p < 0.01), hypernatremia
      incidence (8.27% vs. 15.34%; p = 0.05) and moderate hyperphosphatemia (26.89% vs.
      40.49%; p < 0.02), TPN ending for clinical improve- ment (76.60% vs. 64.40%; p =
      0.04), and reduction of days on TPN (15.74 +/- 20.43 vs. 11.88 +/- 8.34; p <
      0.02), the impaired electrolyte levels significantly improving as a whole. We
      also observed a non-significant trend towards an improvement of adequacy of TPN
      indications, hyperphosphatemia, severe hypophosphatemia, total stay, and post
      surgical stay, in 2003 vs. 2002. CONCLUSIONS: The NSMT experience shows that
      analysis of indicators based on quality standards, in two successive annual
      periods allows assessing the improvement of efficiency of nutritional
      intervention in hospital-admitted patients with TPN with regards to indication,
      assessment, follow-up, and course.

PMID- 16562815
TI  - [Use of ready-to-use (RTU) products in home-based parenteral nutrition].
AB  - AIMS: To analyze the real possibility to use ready-to-use multichamber bags for
      total parenteral nutrition in adult patients on home parenteral nutrition.
      METHODS: In June 2005 we studied the adult patients on home parenteral nutrition
      treatment controlled by the Nutritional Support Unit from an University Hospital.
      Demographic data, data relating to underlying disease state; infusion regimen and
      the necessity to modify it; body mass index, fat free mass index, and Karnofsky
      index evolution, and complications related to parenteral nutrition were assessed.
      RESULTS: At the time of the study, 8 patients aged 48,9 +/- 17,7 years, were on
      home parenteral nutrition. The artificial nutrition treatment was administered
      due to short-bowel syndrome (2); motility disorders (2); suboclusion (2); rapid
      intestinal transit (1), and malabsorption syndrome (1). With the exception of the
      patient who started more recently the treatment, all the others needed changes in
      the parenteral nutrition treatment (number of days for week, or formula
      modification). In general, both the body mass index and the fat free mass index
      increased during the treatment. The Karnofsky index was maintained or increased.
      In relation to catheter-related infection, 4 episodes were observed (0.85/1.000 d
      of HPN). CONCLUSIONS: Due to the effectiveness, safety and the diversity of
      multichamber bags available for parenteral nutrition, and the few complications
      observed in the patients studied, although more studied are necessary, our
      results suggest that we can use this commercial bags for adult patients on home
      parenteral nutrition.

PMID- 16562816
TI  - [National registry of Home Enteral Nutrition in 2003].
AB  - GOAL: To communicate the information available by the NADYA-SENPE Working Group
      from patients on Home Enteral Nutrition (HEN) in our country during the year
      2003. MATERIAL AND METHODS: The data were collected through a closed
      questionnaire included in the web site of the Working Group (www.nadya-senpe.com)
      available only by the authorized users. Variable included were: epidemiological
      information, the indication to prescribe this treatment, the access path, the
      specific nutritional formula used, the treatment duration, the complications and
      hospital readmission related to the nutritional treatment, the follow-up and the
      quality of life. RESULTS: We register 3,858 patients that belong to twenty-one
      hospitals. Mean age from those adults 66.2 +/- 18.9 years, and from those younger
      than 14, 6.0 +/- 4.3 years. Neurological and neoplasic diseases were the
      diagnostics more frequents (38.9% and 37.4%, respectively). Oral nutrition was
      the preferential rout used for the enteral nutrition (54.7%) followed by naso
      enteral tube (26.6%), and only in 17.6% we used ostomy tubes. Polymeric was the
      enteral formula mainly utilized (80.1%). The mean time on HEN was 6.6 +/- 4.3
      months; the 28.8% of patients stayed in the treatment for less than 3 months,
      21.2 % between 3 and 6 months, and 50.0% more than 6 months. Patients were
      followed mainly by Nutritional Support Unit from the reference hospital (73.1%).
      While the reference hospital supplies the material (62.4%), reference hospital
      pharmacy (46.8%) and public pharmacies (32.0%) provides the enteral formula.
      Complications related to enteral nutrition included change of enteral tube
      (44.5%), gastrointestinal complications (30.5%), mechanical complications
      (21.7%), and the metabolic one (3.3%). These complications were followed by 0.02
      hospitalizations/patient. At the end of the year, 54.7% of patients were in the
      HEN programme, and in 35.2 % HEN was finish due to accept oral conventional
      alimentation (49.2%) or by deceased of patients (40.9%). While 26.6% of the
      patients were confined to bed or armchair, 19.7 % no or light discapacity degree
      was observed. CONCLUSIONS: We found a persistence of these treatment in our
      country. Neurological and neoplasic diseases were the more frequent diagnosis in
      patients analysed. The high prevalence of cancer patients could be the main cause
      of oral access for enteral nutrition. Change of enteral tube was the more
      frequent complication observed during this treatment.

PMID- 16562817
TI  - Effects of pork vs veal consumption on serum lipids in healthy subjects.
AB  - AIMS: To analyse the influence of lean pork (P) and veal (V) consumption on the
      lipid profile of healthy subjects within the framework of a healthy diet
      comprising low levels of total fat (TF), saturated fatty acids (SFA) and
      cholesterol. DESIGN: Double-crossover, randomized and controlled trial SUBJECTS:
      44 healthy individuals (22 male and 22 female), recruited voluntarily from the
      University Complutense of Madrid. The weight and lipid profiles of these
      volunteers were normal and their dietary patterns were typical for people in our
      area. INTERVENTIONS: The study comprised 4 phases: stabilisation phase (5 weeks),
      the participants followed their normal diet; second phase (6 weeks), half of the
      subjects, were randomised to lean pork or veal consumption, 150 g per day, for
      their main meal of the day; washout period (5 weeks) and final phase, which was
      the second phase of intervention (6 weeks). During the intervention stages, only
      the main meal of the day was taken in the Hospital. The rest of the subjects'
      diets consisted of different fortnightly menus designed in accordance with the
      recommendations of the Spanish Society of Arteriosclerosis (SEA). RESULTS: After
      both stages of intervention had been completed, there was a mean reduction of
      5.5% in low-density lipoprotein cholesterol. However, after each intervention
      there were no significant differences between those who had consumed P, 2.62
      (0.55) mmol/L and those who had consumed V, 2.71 (0.47) mmol/L. No differences
      were observed in any of the other parameters between those who had consumed P and
      those who had consumed V. CONCLUSIONS: Lean pork and veal produces similar
      effects on the lipid profiles of healthy subjects. Its consumption, as part of
      the saturated fat and cholesterol-controlled diet, could therefore be included in
      food guidelines, both for normal and therapeutic diets.

PMID- 16562818
TI  - [Contribution to the intake of macro and micro nutrients exerted by moderate beer
      consumption].
AB  - OBJECTIVE: Moderate beer consumption can be part of a healthy diet, like the
      Mediterranean diet. The aim of the present study was to analyse the contribution
      a moderate beer consumption makes to energy and nutrient intake in Spanish
      healthy adults. MATERIAL AND METHODS: As part of a larger intervention study,
      dietary intake was measured by means of a 7-day food dietary record in 24 men and
      22 women (age 34.18 +/- 5.80 years) twice: during the last week of the 30 days of
      complete alcohol abstinence and during the last week of 30 days of moderate beer
      consumption. Energy and nutrient content of food was analysed by means of the GEA
      program, based on the Spanish food composition tables. RESULTS: In women,
      moderate beer consumption increased significantly (p < 0.05) mean vitamin B6
      (1.24 +/- 0.32 to 1.47 +/- 0.34 mg), B12 (3.87 +/- 1.46 to 5.58 +/- 2.76 microg),
      A (614.45 +/- 224.75 to 788.3 +/- 486.1 microg), and folate (139.5 +/- 39.88 to
      168.25 +/- 56.32 microg) intake, whereas there was a decrease in mean iodine
      intake (327.1 +/- 148.4 to 281.2 +/- 135.02 microg). In men, mean vitamin B2
      (1.64 +/- 0.62 to 1.91 +/- 0.46 mg), B6 (1.54 +/- 0.63 to 1.80 +/- 0.37 mg),
      niacin (30.01 +/- 8.13 to 34.78 +/- 6.26 mg) and folate (153.23 +/- 68.70 to
      192.32 +/- 46.73 mg) intake also increased significantly. Energy, macronutrient
      and mineral intake had non-significant oscillations. CONCLUSION: Moderate beer
      consumption can improve diet quality in regard to B vitamins in healthy adults.

PMID- 16562819
TI  - Soybean oligosaccharides. Potential as new ingredients in functional food.
AB  - The effects of maturity degree and culture type on oligosaccharide content were
      studied in soybean seed, a rich source of non-digestible galactooligosaccharides
      (GOS). Therefore, two commercial cultivars of yellow soybeans (ripe seeds) and
      two of green soybeans (unripe seeds) were chosen. One yellow and one green
      soybean seed were from intensive culture, while one yellow and one green soybean
      seed were biologically grown. Low molecular weight carbohydrates (LMWC) in
      soybean seeds were extracted with 85% ethanol and determined
      spectrophotometrically and by high performance liquid chromatography. LWC in
      soybean seeds were mainly: stachyose, raffinose and sucrose. Oligosaccharide
      content was not affected significantly, either by biological or intensive culture
      technique. On the contrary, significant differences in GOS content were found
      depending on ripeness degree of soybean seeds. Ripe yellow soybean seeds showed a
      higher oligosaccharide content (1.84-1.95%), than unripe green seeds (1.43
      1.61%). Other LMWC content was also affected by ripeness degree, thus making that
      the relative percentage of GOS was higher in immature (47-53%) than in matured
      soybean seeds (21-34%). Moreover, in order to purify soybean GOS, biologically
      grown yellow soybean seeds with a higher GOS content were selected and a
      previously reported method was followed. Although the GOS containing fraction was
      enriched, the yield obtained was low and an effective purification was not
      achieved. According to these results, yellow soybean seeds seem to be a good
      source of GOS but, in order to improve their purification, simple methods must be
      further developed and evaluated.

PMID- 16562820
TI  - [Quality of data on folic acid content in vegetables included in several Spanish
      Food Composition Tables and new data on their folate content].
AB  - The relationship between adequate folate intake, adequate serum levels, and
      lowering the risk of suffering from cardiovascular diseases, neural tube defects,
      neural illness and some kind of cancers have been widely studied. Because of the
      expected health benefits, the consumption of foods with high folate content or
      enriched foods is increasing. Therefore, an adequate folate intake is important
      in order to reach acceptable serum levels. Reliable food composition data are
      necessary in order to evaluate and estimate the populations folate intake,
      elaborate diets and formulate recommended dietary intakes. For this reason, we
      revised folic acid data in Spanish Food Composition Tables (FCT). The quality of
      the data was evaluated and compared with other well-known international Food
      Composition Tables as well as with a high-resolution liquid chromatographic
      method (HPLC) validated in our laboratory. We evaluated all data about folate
      content, as well as all the information given like data origin, analytical
      method, sampling or original database. For the HPLC method, the food samples were
      incubated with hog kidney conjugase. After that, the samples were purified and
      concentrated by strong anion exchange (SAX), then the folate content was
      quantified by HPLC with a combination of two ultraviolet and fluorescence
      detectors. The evaluation and comparison of data was established according to
      some parameters, which define the quality of data, giving punctuation depending
      on the compliance with these parameters. The study of different sources showed
      that nutrients were different in definition, analysis method, units and
      expression of data, and that this fact could have a potential influence on TCA
      data values. In addition, it has been possible to show a wide variation in food
      number, name of these foods as well as the analysis of raw or cooked products
      with different composition. When the quality conditions were tested, the Spanish
      FCT had the lowest punctuation in folate content data. That is because the
      Spanish FCT did not use a validated method to quantify folic acid in foods
      (Direct method of FCT elaboration), but they used folate content data from others
      FCT (Indirect method of FCT elaboration). These data manifest the importance of
      getting a consensus method to determine folate content in foods with the aim to
      obtain a FCT with reliable folate data.

PMID- 16562821
TI  - [Avascular necrosis of both hips and knees in a patient with ulcerative colitis
      treated for a long term with high-dose corticosteroids].
AB  - INTRODUCTION: Avascular necrosis represents the bone tissue death from
      vascularization failure, and it is mainly associated with the use of high-dose
      corticosteroids for a long time. CLINICAL CASE: A 25 years old female patient
      treated with high-dose corticosteroids for 7 months for ulcerative colitis
      presents with both knees pain and limited hip and knee motility. In a plain X-ray
      and in nuclear magnetic resonance imaging (MRI) avascular necrosis was observed
      at these joints. Bone densitometry showed osteopenia at the femoral head and
      lumbar osteoporosis. DISCUSSION: We present a striking case for its large
      involvement of the joints (both knees and hips) with simultaneous osteoporosis
      and osteopenia in a young patient treated with corticosteroids for ulcerative
      colitis. It is necessary to recommend the judicious use of glucocorticoids,
      prescribing the minimal necessary dose and for the least amount of time necessary
      to control the underlying disease.

PMID- 16562822
TI  - [Management, prevention and control of megaloblastic anemia, secondary to folic
      acid deficiency].
AB  - Folic acid deficiency is the second most common cause of anemia in our
      environment, after anemia secondary to iron deficiency. Folates are essential
      components of human and animal diet. Folic acid is mainly in poliglutamate form,
      and it is hydrolyzed in the proximal jejunum. It is important to identify
      adequately the exact vitamin deficiency that causes megaloblastic anemia, because
      vitamin B12 administration in folate deficiency may correct partially
      megaloblastic alterations, but administration of folic acid in cobalamin
      deficient patients improves haematological parameters but deteriorates the
      neurological syndrome. Main causes of anemia secondary to folate deficiency are
      inadequate dietetic administration, increased requirements, impaired absorption
      and pharmacologic interactions. Folates are altered by light, high temperature
      and by water affinity, which facilitates its elimination by washing or cooking.

PMID- 16562823
TI  - [Home parenteral nutrition in pediatrics. Some answers].

PMID- 16562824
TI  - Special issue in honor of Norman R. Farnsworth.

PMID- 16562825
TI  - Polyphenolic constituents of Actaea racemosa.
AB  - A new lignan, actaealactone (1), and a new phenylpropanoid ester derivative,
      cimicifugic acid G (2), together with 15 known polyphenols, protocatechuic acid,
      protocatechualdehyde, p-coumaric acid, caffeic acid, methyl caffeate, ferulic
      acid, ferulate-1-methyl ester, isoferulic acid, 1-isoferuloyl-beta-d
      glucopyranoside, fukinolic acid, and cimicifugic acids A, B, and D-F, were
      isolated from an extract of the rhizomes and roots of black cohosh (Actaea
      racemosa). The structures of the new compounds were determined on the basis of
      NMR spectroscopic analysis. Compounds 1 and 2 displayed antioxidant activity in
      the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical assay with IC(50) values of
      26 and 37 microM, respectively. Other antioxidants identified from A. racemosa
      include cimicifugic acid A (3), cimicifugic acid B (4), and fukinolic acid (5).
      Compounds 1 and 2 also exhibited a small stimulating effect on the growth of MCF
      7 breast cancer cell proliferation 1.24-fold (14 microM) and 1.14-fold (10
      microM), respectively, compared to untreated cells.

PMID- 16562826
TI  - ent-Labdane diterpenoids from Andrographis paniculata.
AB  - Six new ent-labdane diterpenoids, 3-O-beta-D-glucopyranosyl-14,19
      dideoxyandrographolide (1), 14-deoxy-17-hydroxyandrographolide (2), 19-O-[beta-D
      apiofuranosyl(1-->2)-beta-D-glucopyranoyl]-3,14-dideoxyandrographolide (3), 3-O
      beta-d-glucopyranosylandrographolide (4), 12S-hydroxyandrographolide (5), and
      andrographatoside (6), together with 17 known analogues, were isolated from the
      aerial parts of Andrographis paniculata. The structures of 1-6 were determined by
      spectroscopic data analysis. All compounds isolated were evaluated for their
      inhibitory activity against several bacterial and fungal strains.

PMID- 16562827
TI  - Antineoplastic agents. 551. Isolation and structures of bauhiniastatins 1-4 from
      Bauhinia purpurea.
AB  - Bioassay-guided (P388 lymphocytic leukemia cell line) separation of extracts
      prepared from the leaves, stems, and pods of Bauhinia purpurea, and, in parallel,
      its roots, led to the isolation of four new dibenz[b,f]oxepins (2a, 3-5) named
      bauhiniastatins 1-4, as well as the known and related pacharin (1) as cancer cell
      growth inhibitors. The occurrence of oxepin derivatives in nature is quite rare.
      Bauhiniastatins 1-4 were found to exhibit significant growth inhibition against a
      minipanel of human cancer cell lines, and bauhiniastatin 1 (2a) was also found to
      inhibit the P388 cancer cell line. Structures for these new cancer cell growth
      inhibitors were established by spectroscopic techniques that included HRMS and 2D
      NMR.

PMID- 16562828
TI  - Physalins from Witheringia solanacea as modulators of the NF-kappaB cascade.
AB  - Crude extracts of Witheringia solanacea leaves showed inhibition of NF-kappaB
      activation at 100 microg/mL induced by phorbol 12-myristate-13-acetate (PMA) in
      HeLa cells stably transfected with a luciferase reporter gene controlled by the
      IL-6 promoter. Three physalins were isolated from an active fraction, namely,
      physalins B (1), F (2), and D (3). Of these compounds, 1 and 2 demonstrated
      inhibitory activities on PMA-induced NF-kappaB activation at 16 and 8 microM and
      induced apoptosis after 24 h in a cell-cycle analysis using a human T cell
      leukemia Jurkat cell line. Compound 2 also inhibited TNF-alpha-induced NF-kappaB
      activation at 5 microM through the canonical pathway, but was inactive in the Tet
      On-Luc assay, indicating specificity of action, although it interfered with Tet
      On-Luc at higher concentrations. It is suggested that the presence of a double
      bond and an epoxy ring between carbons 5 and 6 in compounds 1 and 2, respectively
      (which are not present in compound 3), are related to their anti-inflammatory
      activity.

PMID- 16562829
TI  - Cytotoxic constituents from the stem bark of Dichapetalum gelonioides collected
      in the Philippines.
AB  - Fractionation of an ethyl acetate-soluble extract of the stem bark of
      Dichapetalum gelonioides, collected in the Philippines, using the LNCaP (hormone
      dependent human prostate) cell line as a monitor, led to the purification of
      three dichapetalin-type triterpenoids [dichapetalins A (1), I (2), and J (3)],
      along with two dolabrane norditerpenoids (6, 7), and the additional triterpenoids
      zeylanol (8), 28-hydroxyzeylanol (9), and betulinic acid. Since compounds 1-3
      exhibited promising selectivity against the SW626 (human ovarian cancer) cell
      line, a re-collection of the plant material was carried out, to obtain more of
      these compounds for additional biological testing. Two further
      phenylpyranotriterpenoids [dichapetalins K (4) and L (5)] were isolated from the
      re-collected plant material. The structures of the new compounds 2-5 and 9 were
      determined on the basis of spectroscopic data interpretation, and the relative
      configuration of 6 was confirmed using X-ray crystallography. Compounds 4-6 and
      the methyl ester, 6a, exhibited broad cytotoxic activity when tested against a
      panel of human tumor cell lines. Dichapetalin A (1) was not active when evaluated
      in an in vivo hollow fiber assay in the dose range 1-6 mg/kg.

PMID- 16562830
TI  - Cytotoxic xenia diterpenoids from the soft coral Xenia umbellata.
AB  - Eleven new xenia diterpenoids, umbellacins A-G (1-7), 14,15-epoxy-xeniolide H
      (8), 3-acetyl-14,15-epoxy-xeniolide H (9), and umbellacins H and I (10, 11), were
      isolated from a methylene chloride-soluble fraction of the soft coral Xenia
      umbellata. The structures were elucidated by extensive spectroscopic analysis,
      and their cytotoxicity against selected cancer cells was measured in vitro.

PMID- 16562831
TI  - Role of glutamate and dopamine receptors in the psychopharmacological profile of
      the indole alkaloid psychollatine.
AB  - Psychollatine (1), a new glycoside indole monoterpene alkaloid isolated from
      Psychotria umbellata, has shown an interesting psychopharmacological profile.
      This study aimed to investigate the role of NMDA glutamate and dopamine receptors
      in mediating the properties of 1. Psychollatine (1) was assessed for NMDA-induced
      seizures, MK-801-induced hyperlocomotion, amphetamine-induced lethality, and
      apomorphine-induced climbing behavior in mice. Psychollatine (1) (100 mg/kg) and
      MK-801 (0.3 mg/kg) prevented NMDA-induced seizures (P < 0.01), while 1 (100
      mg/kg) attenuated the MK-801-induced hyperlocomotion (P < 0.05). Compound 1 (3
      and 10 mg/kg), as well as chlorpromazine (4 mg/kg), prevented amphetamine-induced
      lethality (P < 0.05). Finally, 1 (10 mg/kg) (P < 0.05), MK-801 (0.2 mg/kg) (P <
      0.01), and chlorpromazine (4 mg/kg) (P < 0.01) attenuated apomorphine-induced
      climbing behavior. The present results strongly support the involvement of NMDA
      glutamate receptors in the mode of action of psychollatine (1).

PMID- 16562832
TI  - Antimalarial compounds from Grewia bilamellata.
AB  - Bioassay-directed fractionation led to the isolation of 12 compounds from a
      sample of the dried leaves, twigs, and stems of Grewia bilamellata. Five of the
      isolates, 3alpha,20-lupandiol (1), grewin (2), nitidanin (4), 2alpha,3beta
      dihydroxy-olean-12-en-28-oic acid (5), and 2,6-dimethoxy-1-acetonylquinol (6),
      showed varying degrees of in vitro antimalarial activity against Plasmodium
      falciparum, but were devoid of significant cytotoxicity to the human oral
      epidermoid KB cancer cell line. Of the 12 isolates, compounds 1, 2, and 3
      (bilagrewin) were determined to be a new triterpene, a new coumarinolignan, and a
      new neolignan, respectively. Other known compounds isolated in this study were 8
      O-4' neolignan guaiacylglycerol-beta-coniferyl ether isomers (threo and erythro),
      cleomiscosin D, icariol A(2), ciwujiatone, and daucosterol. The structures of 1-3
      were elucidated and identified on the basis of spectroscopic data including 1D
      and 2D NMR analysis.

PMID- 16562833
TI  - Turmeric extracts containing curcuminoids prevent experimental rheumatoid
      arthritis.
AB  - Turmeric has been used for centuries in Ayurvedic medicine as a treatment for
      inflammatory disorders including arthritis. On the basis of this traditional
      usage, dietary supplements containing turmeric rhizome and turmeric extracts are
      also being used in the western world for arthritis treatment and prevention.
      However, to our knowledge, no data are available regarding antiarthritic efficacy
      of complex turmeric extracts similar in composition to those available for use as
      dietary supplements. Therefore, the studies described here were undertaken to
      determine the in vivo efficacy of well-characterized curcuminoid-containing
      turmeric extracts in the prevention or treatment of arthritis using streptococcal
      cell wall (SCW)-induced arthritis, a well-described animal model of rheumatoid
      arthritis (RA). Arthritic index, a clinical measure of joint swelling, was used
      as the primary endpoint for assessing the effect of extracts on joint
      inflammation. An essential oil-depleted turmeric fraction containing 41% of the
      three major curcuminoids was efficacious in preventing joint inflammation when
      treatment was started before, but not after, the onset of joint inflammation. A
      commercial sample containing 94% of the three major curcuminoids was more potent
      in preventing arthritis than the essential oil-depleted turmeric fraction when
      compared by total curcuminoid dose per body weight. In conclusion, these data (1)
      document the in vivo antiarthritic efficacy of an essential oil-depleted turmeric
      fraction and (2) suggest that the three major curcuminoids are responsible for
      this antiarthritic effect, while the remaining compounds in the crude turmeric
      extract may inhibit this protective effect.

PMID- 16562834
TI  - Schisandrene, a dibenzocyclooctadiene lignan from Schisandra chinensis: structure
      antioxidant activity relationships of dibenzocyclooctadiene lignans.
AB  - Phytochemical investigation of the fruits of Schisandra chinensis led to the
      isolation of 13 lignans including schisandrene (13), a new lignan based on a
      dibenzocyclooctadiene backbone with an exocyclic double bond. Its structure and
      absolute configuration were established using NMR, MS, and CD data. Antioxidant
      activity of the lignans was evaluated using a DCFH-DA cellular-based assay. The
      structure-activity relationships of the dibenzocyclooctadiene lignans showed that
      the exocyclic methylene functionality was essential for antioxidant activity,
      with the benzoyloxy group probably enhancing such effects.

PMID- 16562835
TI  - Steroidal saponins from the rhizomes of Polygonatum sibiricum.
AB  - Four new steroidal saponins, named neosibiricosides A-D (1-4), were isolated from
      the rhizomes of Polygonatum sibiricum, along with two known spirostanol
      glycosides. The structures of the new glycosides were elucidated by spectroscopic
      methods and acid hydrolysis as (23S,24R,25R)-1-O-acetylspirost-5-ene
      1beta,3beta,23,24-tetrol 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl
      (1-->4)-beta-D-fucopyranoside (1), (25S)-1-O-acetylspirost-5-ene-1beta,3beta-diol
      3-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-beta-D
      glucopyranosyl-(1-->4)-beta-D-galactopyranoside (2), (25S)-spirost-5-en-3beta-ol
      3-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-beta-D
      glucopyranosyl-(1-->4)-2-O-acetyl-beta-D-galactopyranoside (3), and (25R,S)
      spirost-5-en-3beta-ol 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-
      >4)-beta-D-galactopyranoside (4). The cytotoxic activity of the isolated
      compounds was evaluated with human MCF-7 breast cancer cells.

PMID- 16562836
TI  - Isolation and structure assignment of an iminotetrasaccharide from a cultured
      filamentous cyanobacterium Anabaena sp.
AB  - In search of bioactive metabolites in cultured microalgae, a novel acylated
      iminopseudotetrasaccharide was isolated from a filamentous cyanobacterium
      Anabaena sp., and its structure was established by NMR, chemical degradation, and
      X-ray crystallography. The compound consists of glucose, glucuronic acid,
      arabinose, and 1,4,6-trideoxy-1,4-imino-D-allitol, which is closely related to
      potent glucosidase inhibitors such as nojirimycin. The tetrasaccharide itself
      showed moderate inhibitory activity against beta-D-glucuronidase.

PMID- 16562837
TI  - Antiparasitic activity of some xanthones and biflavonoids from the root bark of
      Garcinia livingstonei.
AB  - A new biflavanoid, ent-naringeninyl-(I-3alpha,II-8)-4'-O-methylnaringenin (6),
      along with five known xanthones and two known biflavonoids, was isolated from the
      root bark of Garcinia livingstonei collected in Tanzania. The absolute
      configuration of 6 was established by CD spectroscopy. This compound showed
      moderate activity against P. falciparum (IC(50) 6.7 microM). Antitrypanosomal
      activity (IC(50) 0.87 microM) was observed for 1,4,5-trihydroxy-3-(3-methylbut-2
      enyl)-9H-xanthen-9-one (3). The dimeric xanthone garcilivin A (4) showed a higher
      and nonselective antiparasitic activity and cytotoxicity (IC(50) 2.0 microM
      against MRC-5 cells) than its diastereoisomer garcilivin C (5) (IC(50) 52.3
      microM).

PMID- 16562838
TI  - Bioactive isomalabaricane triterpenoids from Rhabdastrella globostellata that
      stabilize the binding of DNA polymerase beta to DNA.
AB  - Four isomalabaricane triterpenoids were isolated from an extract of the sponge
      Rhabdastrella globostellata that was active in an assay measuring stabilization
      of the binding of DNA with DNA polymerase beta. The known compounds stelliferin
      riboside (1) and 3-epi-29-acetoxystelliferin E (2) were shown to induce 29% and
      23% binding, respectively, at 28 microg/mL, while the new compound stellettin J
      (3) induced 5% binding at 28 microg/mL. The new compound stellettin K (4) had no
      activity in the binding assay. The compounds were characterized by spectroscopic
      methods. These compounds displayed varying levels of activity toward the A2780
      ovarian cancer cell line, revealing structure-based effects on both the level of
      cytotoxicity and DNA-polymerase beta binding. This is the first report of natural
      products with the ability to promote stabilization of the DNA-polymerase beta
      covalent binary complex.

PMID- 16562839
TI  - Discovery of bacterial fatty acid synthase inhibitors from a Phoma species as
      antimicrobial agents using a new antisense-based strategy.
AB  - Fatty acids are essential for bacterial growth and viability, with the type II
      fatty acid synthesis (FAS II) pathway being a potential antibacterial target. A
      new, selective, and highly sensitive whole cell-based antisense strategy has been
      designed to screen for natural product inhibitors of FabH/F of the FAS II pathway
      using a high-throughput two-plate agar-based differential sensitivity assay
      (FabF(2)p). An antisense assay along with the FASII enzyme prepared from
      Staphylococcus aureus was used for bioactivity-guided fractionation, leading to
      the isolation of phomallenic acids A-C (1-3) from a leaf litter fungus identified
      as Phoma sp. Compounds 1-3 exhibited minimum detection concentrations (MDC) of
      0.63, 0.31, and 0.15 microg/mL in the FabF(2P) assay, IC(50) values of 22, 3.4,
      and 0.77 microg/mL in the FASII enzyme assay, and minimum inhibitory
      concentrations (MIC) of 250, 7.8, and 3.9 microg/mL, respectively, against wild
      type S. aureus. Phomallenic acid C (3), the analogue with the longest chain,
      exhibited the best overall activity within the phomallenic acids obtained and was
      superior to cerulenin and thiolactomycin, the two most studied and commonly used
      FabF inhibitors.

PMID- 16562840
TI  - (+)-agelasine D: improved synthesis and evaluation of antibacterial and cytotoxic
      activities.
AB  - An improved synthesis of (+)-agelasine D (10) from (+)-manool is reported
      together with cytotoxic and antibacterial data for agelasine D and structurally
      close synthetic analogues. These compounds display a broad spectrum of
      antibacterial activities including effects on M. tuberculosis and Gram-positive
      and Gram-negative bacteria (both aerobes and anaerobes). They exhibit profound
      cytotoxic activity against several cancer cells, including a multidrug-resistant
      cell line. (+)-Agelasine D (10) has been isolated earlier from a marine sponge
      (Agelas sp.).

PMID- 16562841
TI  - Polyketide chain skipping mechanism in the biosynthesis of the hybrid
      nonribosomal peptide-polyketide antitumor antibiotic leinamycin in Streptomyces
      atroolivaceus S-140.
AB  - A fundamental feature of modular polyketide synthases (PKSs) is the highly
      predictable relationship between the domain order and the chemical functional
      groups of resultant polyketide products. Sequence analysis and biochemical
      characterization of the leinamycin (LNM) biosynthetic gene cluster from
      Streptomyces atroolivaceus S-140 has revealed a gene, lnmJ, that encodes five PKS
      modules but with six acyl carrier protein (ACP) domains. The LnmJ PKS module 6
      contains two ACP domains, ACP(6-1) and ACP(6-2), separated by a C
      methyltransferase domain. Site-directed mutagenesis experiments were carried out
      with each of these ACPs to test alternative mechanisms proposed for their role in
      polyketide chain elongation. The in vivo results revealed a new type of
      polyketide chain "skipping" mechanism, in which either ACP is sufficient for LNM
      biosynthesis. Biochemical characterization in vitro showed that both ACPs can be
      loaded with a malonate extender unit by the LnmG acyl transferase; however, ACP(6
      2) appears to be preferred because the loading efficiency is about 5-fold that of
      ACP(6-1). The results are consistent with ACP(6-2) being used for the initial
      chain elongation step wth ACP(6-1) being involved in the ensuing C-methylation
      process. These findings provide new insights into the polyketide chain skipping
      mechanism for modular PKSs.

PMID- 16562842
TI  - Sylviside, a diterpene glucoside derivative from Gnaphalium sylvaticum.
AB  - A new diterpene glucoside (1), named sylviside, was isolated from the aerial
      parts of Gnaphalium sylvaticum. Its structure was elucidated as
      2beta,15alpha,20alpha-trihydroxy-19,20-dicarboxy-ent-kaur-16-ene 2beta-O-(2'
      angelate)-beta-D-glucopyranoside, on the basis of spectroscopic analysis ((1)H
      NMR, (13)C NMR, HMQC, HMBC, NOESY), and was confirmed by X-ray crystallographic
      analysis. Sylviside (1) displayed weak cytotoxicity against HeLa WT (human
      epitheloid cervical carcinoma) cells and was also evaluated for its effects on
      reversing multidrug resistance in HeLa cells overexpressing MDR1.

PMID- 16562843
TI  - Rautandiols A and B, pterocarpans and cytotoxic constituents from Neorautanenia
      mitis.
AB  - As part of a study on potential antitumor agents from rainforest plants, two new
      pterocarpans, rautandiol A (1) and rautandiol B (2), together with eight known
      compounds, were isolated from Neorautanenia mitis. Among the compounds isolated,
      rotenone (3) and 12-hydroxyrotenone (4) showed significant cytotoxic activity
      with IC(50) values of 0.008-0.010 and 0.04-0.06 microg/mL against MCF-7 and A-549
      cells, respectively.

PMID- 16562844
TI  - Alkaloids from the roots of Aconitum pseudo-laeve var. erectum.
AB  - One new quinazoline (1) and two new norditerpenoid (2 and 3) alkaloids along with
      10 known compounds were isolated from the roots of Aconitum pseudo-laeve var.
      erectum. The new alkaloids were assigned as 2-(2-methyl-4-oxo-4H-quinazoline-3
      yl)benzoic acid methyl ester (1), 18-O-2-(2-methyl-4-oxo-4H-quinazoline-3
      yl)benzoyllycoctonine (2), and 14-O-acetyl-8-O-methyl-18-O-2-(2-methyl-4-oxo-4H
      quinazoline-3-yl)benzoylcammaconine (3). The structures of the new alkaloids were
      established by spectroscopic methods. This is the first report of the 2-(2-methyl
      4-oxo-4H-quinazoline-3-yl)benzoyl ester group being found as an acyl substituent
      in norditerpenoid alkaloids (compounds 2 and 3).

PMID- 16562845
TI  - Andropanolide and isoandrographolide, minor diterpenoids from Andrographis
      paniculata: structure and X-ray crystallographic analysis.
AB  - Phytochemical investigation of the leaves of Andrographis paniculata has led to
      the isolation of a new labdane type diterpenoid, andropanolide (1), along with
      seven known diterpenoids including isoandrographolide (2), previously reported as
      a rearrangement product of andrographolide. The structures and stereochemistry of
      compounds 1 and 2 were established by X-ray crystallographic analysis.

PMID- 16562846
TI  - Polyacylated oligosaccharides from medicinal Mexican morning glory species as
      antibacterials and inhibitors of multidrug resistance in Staphylococcus aureus.
AB  - Twenty-two convolvulaceous oligosaccharides selected from the tricolorin (1-7),
      scammonin (8, 9), and orizabin (10-22) series were evaluated for activity against
      a panel of Staphylococcus aureus strains possessing or lacking specific efflux
      pumps. The minimum inhibitory concentrations (MIC values) for most of the
      amphipatic compounds ranged from 4 to 32 microg/mL against XU-212 (possessing the
      TetK multidrug efflux pump) and SA-1199B (overexpressing the NorA multidrug
      efflux pump), compared with 64 and 0.25 microg/mL, respectively, for
      tetracycline. This activity was shown to be bactericidal. Two microbiologically
      inactive members of the orizabin series (10, 20) increased norfloxacin
      susceptibility of strain SA-1199B. At low concentrations, compound 10 was a more
      potent inhibitor of multidrug pump-mediated EtBr efflux than reserpine. The wide
      range of antimicrobial activity displayed by these compounds is an example of
      synergy between related components occurring in the same medicinal crude drug
      extract, i.e., microbiologically inactive components disabling a resistance
      mechanism, potentiating the antibiotic properties of the active substances. These
      results provide an insight into the antimicrobial potential of these complex
      macrocyclic lactones and open the possibility of using these compounds as
      starting points for the development of potent inhibitors of S. aureus multidrug
      efflux pumps.

PMID- 16562847
TI  - Cytotoxic and antimicrobial benzophenones from the leaves of Tovomita longifolia.
AB  - Bioassay-guided fractionation of the chloroform and ethanol extracts of Tovomita
      longifolia leaves using cytotoxic and antimicrobial assays resulted in the
      isolation of four new benzophenones, (E)-3-(2-hydroxy-7-methyl-3-methyleneoct-6
      enyl)-2,4,6-trihydroxybenzophenone (1), (E)-3-(6-hydroxy-3,7-dimethylocta-2,7
      dienyl)-2,4,6-trihydroxybenzophenone (2), 8-benzoyl-2-(4-methylpenten-3
      yl)chromane-3,5,7-triol (3), and 5-benzoyl-1,1,4a-trimethyl-2,3,4,4a,9,9a
      hexahydro-1H-xanthene-6,8-diol (4), and two known benzophenones, 4-geranyloxy-2,6
      dihydroxybenzophenone (5) and 3-geranyl-2,4,6-trihydroxybenzophenone (6). The
      structures of 1-4 were established by spectroscopic means and by molecular
      modeling calculations. Compounds 1 and 3-5 demonstrated cytotoxic activities
      against breast (MCF-7), central nervous system (SF-268), and lung (H-460) human
      cancer cell lines, while compounds 3-6 showed antimicrobial activity against
      Klebsiella pneumoniae, Mycobacterium smegmatis, Pseudomonas aeruginosa,
      Salmonella gallinarum, and Staphylococcus aureus.

PMID- 16562848
TI  - Tropane aromatic ester alkaloids from a large-scale re-collection of Erythroxylum
      pervillei stem bark obtained in Madagascar.
AB  - Fractionation by pH zone-refining countercurrent chromatography of an extract of
      the stem bark of Erythroxylum pervillei, obtained on a kilogram scale in southern
      Madagascar, led to the isolation and characterization of four tropane aromatic
      ester alkaloids as minor constituents, namely, pervilleines G (5) and H (6) and
      cis-pervilleines B (7) and F (8). Their structures were determined by
      spectroscopic data interpretation.

PMID- 16562849
TI  - Daphmanidins E and F, alkaloids from Daphniphyllum teijsmannii.
AB  - Two new Daphniphyllum alkaloids, daphmanidins E (1) and F (2), have been isolated
      from the leaves of Daphniphyllum teijsmannii, and the structures were elucidated
      on the basis of spectroscopic data. Daphmanidins E and F showed a moderate
      vasorelaxant effect on rat aorta.

PMID- 16562850
TI  - Bioactive dammarane triterpenes from the mangrove plant Bruguiera gymnorrhiza.
AB  - Three new dammarane triterpenes, bruguierins A-C (1-3), were isolated from a
      petroleum ether extract of the flowers of Bruguiera gymnorrhiza. Their structures
      were determined on the basis of physical and spectroscopic data interpretation.
      With stably transfected HepG2 cells, the three isolates activated antioxidant
      response element (ARE luciferase activation) with EC(50) values of 7.8, 9.4, and
      15.7 microM, respectively. Bruguierin A (1) also inhibited phorbol ester-induced
      NFkappaB (nuclear factor-kappaB) luciferase activation with an IC(50) value of
      1.4 microM and selectively inhibited cyclooxygenase-2 (COX-2) activity with an
      IC(50) value of 0.37 microM. Compounds 2 and 3 were not active in these
      bioassays.

PMID- 16562851
TI  - Actinofuranones A and B, polyketides from a marine-derived bacterium related to
      the genus streptomyces (actinomycetales).
AB  - Two new polyketides, actinofuranones A (1) and B (2), were isolated from the
      culture extract of a marine-derived Streptomyces strain designated CNQ766. The
      structures of 1 and 2 were elucidated by interpretation of NMR and other
      spectroscopic data and by chemical derivatization. The relative stereochemistries
      of these new molecules were assigned on the basis of analysis of NOE data and
      vicinal (1)H-(1)H coupling constants, while the absolute configurations of the
      asymmetric centers were determined using the modified Mosher's method.

PMID- 16562852
TI  - A concise synthesis of ginkgolide M, a minor component of a terpene trilactone
      fraction from ginkgo biloba roots.
AB  - Ginkgolide M (GM), which is found only in the roots of the Ginkgo biloba tree and
      is an inhibitor of ligand-operated ion channels in the central nervous system,
      has been prepared in three steps from 10-benzylginkgolide C, an intermediate
      generated during the isolation and separation of ginkgolides from Ginkgo biloba
      leaf extract. The described synthetic sequence can be applied to access GM
      derivatives for biological studies.

PMID- 16562853
TI  - Alkaloids from Eschscholzia californica and their capacity to inhibit binding of
      [3H]8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A receptors in Vitro.
AB  - A 70% ethanol extract of California poppy (Eschscholzia californica) was able to
      bind to 5-HT(1A) and 5-HT(7) receptors at 100 mug/mL. The subsequent isolation
      procedure yielded the known alkaloids californidine (1), escholtzine (2), N
      methyllaurotetanine (3), caryachine (4), and O-methylcaryachine (5), along with a
      new pavine alkaloid, 6S,12S-neocaryachine-7-O-methyl ether N-metho salt (7). The
      structure of 7 was determined by spectroscopic data interpretation, while the
      absolute stereochemistry was determined by means of circular dichroism. From the
      results obtained from the radioligand-binding assay of the pure compounds,
      including the commercially available protopine (6), it was evident that the
      activity on the 5-HT(1A) receptor was at least partly due to the presence of the
      aporphine alkaloid 3, which showed the highest inhibition of [(3)H]8-hydroxy-2
      (di-N-propylamino)tetralin ([(3)H]8-OH-DPAT) binding with an EC(50) value of 155
      nM and a K(i) of 85 nM.

PMID- 16562854
TI  - (+)-N-Deoxymilitarinone A, a neuritogenic pyridone alkaloid from the insect
      pathogenic fungus Paecilomyces farinosus.
AB  - A new pyridone alkaloid, (+)-N-deoxymilitarinone A (1), was isolated from
      Paecilomyces farinosus RCEF 0097 along with the related metabolites, militarinone
      D and militarinone B. The sterol 22E,4R-ergosta-7,22-diene
      3beta,5alpha,6beta,9alpha-tetraol was also identified. The structures were
      established by spectroscopic methods, in particular with the aid of extensive NMR
      experiments. Compound 1 induced neurite sprouting in PC 12 cells when tested at
      33 and 100 microM concentrations. A cytotoxic effect was observed in human
      neurons (IMR-32) at a concentration of 100 microM.

PMID- 16562855
TI  - N-Methyl-4-hydroxy-2-pyridinone analogues from Fusarium oxysporum.
AB  - Three new N-methyl-4-hydroxy-2-pyridinone analogues, 6-epi-oxysporidinone (3),
      the dimethyl ketal of oxysporidinone (4), and N-demethylsambutoxin (5), along
      with the known compounds (-)-oxysporidinone (1), (-)-sambutoxin (2), wortmannin
      (6), enniatin A (7), enniatin A1 (8), and enniatin B1 (9) were isolated from
      Fusarium oxysporum (N17B) by bioassay-guided fractionation. Compounds 1 and 3
      showed selective fungistatic activity against Aspergillus fumigatus, and
      wortmannin had selective potent activity against Candida albicans. Moderate
      activity was observed with the enniatins 7-9 against C. albicans, Cryptococcus
      neoformans, and Mycobacterium intracellulare. Compounds 1-5 had no activity
      against the agriculturally important fungi Fusarium verticillioides (syn. F.
      moniliforme) and Aspergillus flavus.

PMID- 16562856
TI  - Astaxanthin, a carotenoid with potential in human health and nutrition.
AB  - Astaxanthin (1), a red-orange carotenoid pigment, is a powerful biological
      antioxidant that occurs naturally in a wide variety of living organisms. The
      potent antioxidant property of 1 has been implicated in its various biological
      activities demonstrated in both experimental animals and clinical studies.
      Compound 1 has considerable potential and promising applications in human health
      and nutrition. In this review, the recent scientific literature (from 2002 to
      2005) is covered on the most significant activities of 1, including its
      antioxidative and anti-inflammatory properties, its effects on cancer, diabetes,
      the immune system, and ocular health, and other related aspects. We also discuss
      the green microalga Haematococcus pluvialis, the richest source of natural 1, and
      its utilization in the promotion of human health, including the antihypertensive
      and neuroprotective potentials of 1, emphasizing our experimental data on the
      effects of dietary astaxanthin on blood pressure, stroke, and vascular dementia
      in animal models, is described.

PMID- 16562857
TI  - Soy isoflavones and bone health: a double-edged sword?
AB  - Numerous publications and research studies on isoflavones have prompted a
      nationwide increase in the consumption of soy-based foods and supplements in the
      United States. Isoflavones are natural endocrine active compounds generally
      considered to promote health and prevent or slow the onset of certain chronic
      diseases such as osteoporosis. The beneficial effects of soy isoflavones on bone
      may, however, be life-stage specific and dependent on the estrogen receptor
      number and endogenous hormone milieu. Perimenopausal and early menopausal women
      may therefore be more receptive to the therapeutic effects of isoflavones on bone
      loss prior to the diminution of estrogen receptors that occurs in the
      postmenopausal years, whereas laboratory studies in developmental age range
      animals have demonstrated the potential for adverse effects following exposure to
      high levels of soy isoflavones. Clinical studies in developing humans that either
      support or refute findings in animal studies are lacking. The effects of chronic
      consumption of high levels of soy isoflavones at each life stage to assess risk
      benefit ratios should be a high priority of research.

PMID- 16562858
TI  - Quinone reductase induction as a biomarker for cancer chemoprevention.
AB  - Chemoprevention involves the use of natural or synthetic substances to reduce the
      risk of developing cancer. Strategies for protecting cells from initiation events
      include decreasing metabolic enzymes responsible for generating reactive species
      (phase I enzymes) while increasing phase II enzymes that can deactivate radicals
      and electrophiles known to intercede in normal cellular processes. Reduction of
      electrophilic quinones by quinone reductase is an important detoxification
      pathway. Following evaluation of approximately 3000 plant and marine organism
      extracts, the number characterized as "active" was established in the range of
      12% of the total, and over 60 active compounds have been isolated as quinone
      reductase inducers. One of them, isoliquiritigenin (1), isolated from tonka bean,
      was shown to be a monofunctional inducer by having similar quinone reductase
      inducing ability in wild-type Hepa 1c1c7 cells and two mutant cell lines. To
      further investigate the mechanism of induction, HepG2 human hepatoma cells stably
      transfected with ARE-luciferase plasmid were used. Isoliquiritigenin (1)
      significantly induced the luciferase activity in a dose-dependent manner. On the
      basis of these results, a full-term cancer chemoprevention study was conducted
      with 7,12-dimethylbenz[a]anthracene (DMBA)-treated female Sprague-Dawley rats.
      Dietary administration of 1 increased tumor latency. Based on these promising
      preliminary results, additional mechanistic studies are underway, as well as full
      term carcinogenesis studies with chronic administration schedules.

PMID- 16562859
TI  - The development of USP botanical dietary supplement monographs, 1995-2005.
AB  - The development of USP botanical dietary supplement monographs by the
      Subcommittee on Natural Products (1995-2000) and the Dietary Supplements
      Botanicals Committee of Experts (2000-2005) of the USP is described in this
      review. Featured details include the USP as an organization, focusing upon its
      history, mission, and publication of the United States Pharmacopeia-National
      Formulary (USP-NF); the formulation and composition of botanical dietary
      supplement monographs and related general chapters, as well as appropriate
      admission criteria; and a summary of the accomplishments of the Committees (1995
      2005).

PMID- 16562860
TI  - "Studies on biodiversity of Vietnam and Laos" 1998-2005: examining the impact.
AB  - The impact of the University of Illinois at Chicago-based Vietnam-Laos
      International Cooperative Biodiversity Group (ICBG) Program "Studies on
      Biodiversity of Vietnam and Laos", which has been in operation for the period of
      1998-2005, touches on five major areas of endeavor: (a) biodiversity inventory
      and conservation; (b) studies on medicinal plants; (c) drug discovery and
      development; (d) economic development; and (e) issues on intellectual property
      rights and benefit sharing in natural products drug discovery and development.
      Highlights are presented and the significance is discussed.

PMID- 16562861
TI  - Bioactive triterpenoids from Salvia species.
AB  - Salvia species are important medicinal and culinary plants, and they have been
      the subject of numerous chemical and biological studies. The bioactive
      triterpenoids of Salvia species, reported in the literature to date, are
      reviewed. About 200 triterpenoids, almost 80 of which are new, isolated, and
      characterized from about 100 Salvia species, are presented herein. In addition to
      the diverse biological activities of the pure triterpenoids, studies on
      biological activity of extracts of Salvia species are also described.

PMID- 16562862
TI  - Natural product extracts of plant and marine origin having antileukemia
      potential. The NCI experience.
AB  - While effective treatments exist for acute lymphocytic leukemia (ALL),
      particularly in the case of children, and for chronic mylogenous leukemia (CML),
      more efficacious treatments for other forms of acute and chronic forms of the
      disease are still needed. The National Cancer Institute has tested over 90,000
      extracts of terrestrial plants and marine plants and invertebrates in its human
      cancer one-dose/60-cell-line prescreen, and the results for plants and marine
      organisms meeting criteria established for activity against selected leukemia
      cell lines are presented. Taxonomic data are limited to family and genus in the
      case of plants, and phylum for marine organisms, and those groups of organisms
      exhibiting significant activity (so-called "hot" families and genera) are
      discussed. The "hot" terrestrial plant families Myrsinaceae and Sapindaceae have
      not been studied to any extent and appear to merit special attention, although
      leukemia cell line selectivity is also noted for other families.

PMID- 16562863
TI  - Microbial and enzymatic transformations of flavonoids.
AB  - Flavonoids are among the most ubiquitous phenolic compounds found in nature.
      These compounds have diverse physiological and pharmacological activities such as
      estrogenic, antitumor, antimicrobial, antiallergic, and anti-inflammatory
      effects. They are well-known antioxidants and metal ion-chelators. In the present
      review, biotransformations of numerous flavonoids catalyzed mainly by microbes
      and few plant enzymes are described in four different flavonoid classes, viz.,
      chalcones, isoflavones, catechins, and flavones. Both phase I (oxidative) and
      phase II (conjugative) biotransformations representing a variety of reactions
      including condensation, cyclization, hydroxylation, dehydroxylation, alkylation,
      O-dealkylation, halogenation, dehydrogenation, double-bond reduction, carbonyl
      reduction, glycosylation, sulfation, dimerization, or different types of ring
      degradations are elaborated here. In some cases, the observed microbial
      transformations mimic mammalian and/or plant metabolism. This review recognizes
      Norman Farnsworth, who through his fascination and hard work in pharmacognosy has
      fostered the excitement of discovery by numerous students and faculty far and
      beyond the halls of the University of Illinois at Chicago. It is with grateful
      thanks for these efforts that we dedicate this review to him.

PMID- 16562865
TI  - Persistence of paratropic ring currents in nonplanar, tub-shaped geometries of
      1,3,5,7-cyclooctatetraene.
AB  - [reaction: see text] Surprisingly, the anti-aromatic paratropic ring current of
      the planar D(4)(h) transition state of 1,3,5,7-cyclooctatetraene (COT) survives
      almost all the way to the equilibrium tub-shaped D(2)(d) COT structure (plane-to
      plane distance, d = 0.76 A); the current vanishes at ca. 80% of the geometric
      change and ca. 90% of the energy change from planar to tub geometry.

PMID- 16562864
TI  - Natural products from plant-associated microorganisms: distribution, structural
      diversity, bioactivity, and implications of their occurrence.
AB  - A growing body of evidence suggests that plant-associated microorganisms,
      especially endophytic and rhizosphere bacteria and fungi, represent a huge and
      largely untapped resource of natural products with chemical structures that have
      been optimized by evolution for biological and ecological relevance. A diverse
      array of bioactive small molecule natural products has been encountered in these
      microorganisms. The structures of over 230 metabolites isolated and characterized
      from over 70 plant-associated microbial strains during the past four years are
      presented with information on their hosts, culture conditions, and biological
      activities. Some significant biological and ecological implications of their
      occurrence are also reviewed.

PMID- 16562866
TI  - Cyclic semipeptoids: peptoid-organic hybrid macrocycles.
AB  - [structure: see text] Cyclic semipeptoids 1 and 2 represent constrained,
      secondary structure mimics where the R(1) and R(2) side chains correspond to
      those of amino acids. Solid-phase syntheses and conformational analyses of these
      compounds are described.

PMID- 16562867
TI  - Design of highly enantioselective organocatalysts based on molecular recognition.
AB  - [reaction: see text] Various organocatalysts have been designed based on
      molecular recognition to catalyze the asymmetric direct aldol reaction of ketones
      with aryl and alkyl alpha-keto acids, affording beta-hydroxyl carboxylic acids
      with a tertiary stereogenic center with excellent enantioselectivities of up to
      98% ee. A linear effect was observed for the reaction, demonstrating a single
      molecule of the catalyst involved in the catalysis.

PMID- 16562868
TI  - Multi[2]rotaxanes with gold nanoparticles as centers.
AB  - [structure: see text] The multi[2]rotaxanes with gold nanoparticles as centers
      are constructed by introducing chromophoric beta-cyclodextrin-based [2]rotaxanes
      on the surface of gold nanoparticles, which show good photophysical and
      electrochemical properties superior to the parent rotaxane.

PMID- 16562869
TI  - From nonfunctional lamellae to functional nanotubes.
AB  - [structure: see text] Long chain alkyl-alkyl interactions appears to be the main
      driving force in hydrogen bond isomerism induced transformation of lamellar
      architectures to nanotubular constructs in alkylammonium dicarboxylate salts; the
      syntheses of the nanotubes require no skill for typical organic synthesis, and
      they are functional materials displaying intriguing gelling properties.

PMID- 16562870
TI  - Two new chiral EDTA-based metal chelates for weak alignment of proteins in
      solution.
AB  - [structure: see text] A short synthesis of EDTA-based metal chelates that can be
      attached to the cysteine residue of a protein via a disulfide bond is described.
      The complexes were used after coordination of lanthanides to align trigger factor
      and apo-calmodulin in solution to yield residual dipolar couplings and
      pseudocontact shifts. Alignment tensors for the new tags are linearly independent
      compared to those of previously published tags.

PMID- 16562871
TI  - Unusually weak binding interactions in tetrazole-amidine complexes.
AB  - [reaction: see text] Tetrazoles frequently replace carboxylic acids in
      pharmaceutical drugs. However, while the binding modes of tetrazolate and
      carboxylate anions in amidinium complexes turns out to be similar, the
      association constant of the former is 2-3 orders of magnitude smaller in DMSO.
      Crystal structures revealed that the N...H-N hydrogen bonds in amidinium
      tetrazolates are bent (162 degrees and 169 degrees ) and noticeably longer (N...N
      2.96 A) than corresponding hydrogen bonds in both amidinium carboxylates and
      ammonium tetrazolates.

PMID- 16562872
TI  - Synthesis of (+)-sch 642305 by a biomimetic transannular Michael reaction.
AB  - [reaction: see text] The synthesis of (+)-Sch 642305 (1) has been completed in 17
      steps in 1.6% overall yield. Transannular Michael reaction of 2b with NaH in THF
      provided cyclohexenone 23 stereospecifically. Heating 23 in TFA/CDCl(3) provided
      a 3:1 equilibrium mixture of 23 and 25, which was hydrolyzed to give (+)-6-epi
      Sch 642305 (24) and (+)-Sch 642305 (1), respectively.

PMID- 16562873
TI  - Catalytic asymmetric addition of dimethylzinc to alpha-ketoesters, using
      mandelamides as ligands.
AB  - [reaction: see text] A strategy based on the control of the electron-donating
      capabilities of the coordinating groups of the ligand has been applied in the
      catalytic asymmetric addition of organometallic reagents to ketoesters.
      Mandelamides having deprotonated alcohol and carboxyamido groups catalyzed the
      addition of dimethylzinc to alpha-ketoesters with good yields and ee (up to 90%).

PMID- 16562874
TI  - Selective magnesiation of chloro-iodopurines: an efficient approach to new purine
      derivatives.
AB  - [reaction: see text] Both 6-chloro-2-iodo-9-isopropylpurine (1) and 2-chloro-6
      iodo-9-benzylpurine (4) undergo a selective I/Mg exchange reaction with iPrMgCl
      at -80 degrees C. The reaction course at 0 degrees C is different. Magnesiation
      of 1 proceeds with the migration of magnesium to the 8 position of the purine
      nuclei. In the case of 4, substitution of iodine with an alkyl group from the
      Grignard reagent accompanied with a Cl/Mg exchange reaction takes place, and 6
      alkyl-2-magnesiated purines (9) are formed. Thus prepared Grignard reagents
      afford the corresponding alcohols by the reaction with aldehydes.

PMID- 16562875
TI  - Formal total synthesis of (-)-emetine using catalytic asymmetric allylation of
      cyclic imines as a key step.
AB  - [reaction: see text] Catalytic asymmetric allylation of 3,4-dihydro-6,7
      dimethoxyisoquinoline was carried out using allyltrimethoxysilane in the presence
      of Cu(I) and tol-BINAP. The allyl adduct thus obtained was transformed to a
      chiral synthetic intermediate for (-)-emetine in good yield. The procedure was
      applied to the total synthesis of ent-emetine.

PMID- 16562876
TI  - Stereoselective synthesis of alpha-C-Substituted 1,4-dideoxy-1,4-imino-D
      galactitols. Toward original UDP-Galf mimics via cross-metathesis.
AB  - [reaction: see text] Various alpha-C-substituted 1,4-dideoxy-1,4-imino-d
      galactitols were prepared efficiently from 1-O-acetyl-2,3,5,6-tetra-O-benzyl-d
      glucofuranose by a four-step sequence involving as the key step the highly syn
      selective TMSOTf-catalyzed addition of silylated nucleophiles to a
      glycofuranosylamine. Cross-metathesis of the alpha-C-allylated
      iminogalactofuranose derivative with an original uridin-5'-yl vinylphosphonate
      led to novel UDP-galactofuranose mimics. Such compounds are of interest as
      potential inhibitors of the mycobacterial galactan biosynthesis pathway.

PMID- 16562877
TI  - Desulfonylation with Mg-MeOH-NiBr(2): an expedient reagent system for the
      synthesis of 2-amino-2,3-dideoxy furanosides.
AB  - [reaction: see text] A catalytic amount of NiBr(2) with Mg-MeOH increases the
      efficiency of reductive desulfonylation of the beta-sulfonylated aminosugars. The
      Mg-MeOH-NiBr(2) system has been utilized in the synthesis of 2-amino-2,3
      dideoxypentofuranosides and 2-amino-2,3-dideoxyhexofuranosides. The yield of the
      desulfonylation improved dramatically from 0% with the known reagents to 44-75%
      with Mg-MeOH-NiBr(2).

PMID- 16562878
TI  - New versatile building block for the construction of tetrathiafulvalene-based
      donor-acceptor systems.
AB  - [reaction: see text] A new dissymmetrical tetrathiafulvalene (TTF) derivative 1
      was synthesized as a versatile building block to reach TTF-based donor-acceptor
      assemblies incorporating C(60) in triad C(60)-TTF-C(60) 2 and/or p-benzoquinone
      (Q) in fused dyad Q-TTF 3 and triad Q-TTF-C(60) 4.

PMID- 16562879
TI  - Design and synthesis of bismacrocyclic hexaazatriphenylene derivatives.
AB  - [reaction: see text] The first examples of bismacrocyclic derivatives of
      2,3,6,7,10,11-hexaphenyl-1,4,5,8,9,12-hexaazatriphenylene are described. They are
      obtained by the condensation of a linear trisbenzil precursor with
      hexaaminobenzene.

PMID- 16562880
TI  - Synthesis of (+/-)-3-Methoxyestra-1,3,5(10)-trienes by the repetitive use of
      Negishi reagent.
AB  - [reaction: see text] The repetitive use of Cp(2)ZrBu(2) (Negishi reagent) was
      applied in the synthesis of three 3-methoxyestra-1,3,5(10)-trienone isomers
      within four steps from the advanced intermediate 11. The overall synthesis is
      based on three zirconium-mediated reactions: (a) oxidative addition of a benzyl
      ether, (b) cyclization of an allyl-ene compound, and (c) cyclocarbonylation of a
      diene. The presented synthesis demonstrates that complex organic compounds can be
      prepared by the repetitive use of one reagent.

PMID- 16562881
TI  - Tryptophan 232 within oxidosqualene-lanosterol cyclase from Saccharomyces
      cerevisiae influences rearrangement and deprotonation but not cyclization
      reactions.
AB  - [reaction: see text] Oxidosqualene-lanosterol cyclases convert oxidosqualene to
      lanosterol in yeast and mammals. Site-saturated mutants' construction of
      Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase, at Trp232 exchanges
      against proteinogenic amino acids, and product profiles are shown. All mutants,
      except Lys and Arg, produced protosta-12,24-dien-3beta-ol, lanosterol, and
      parkeol. Overall, Trp232 plays a catalytic role in the influence of rearrangement
      process and determination of deprotonation position but does not involve
      intervention in the cyclization steps.

PMID- 16562882
TI  - Electroreductive intramolecular coupling of aromatic imino esters: is four
      membered cyclization much more favorable than six-membered cyclization?
AB  - [reaction: see text] The electroreduction of an aromatic imino ester prepared
      from (S)-glutamic acid in the presence of chlorotrimethylsilane and triethylamine
      afforded a four-membered cyclized product, a mixed ketal of cis-2,4-disubstituted
      azetidine-3-one, stereospecifically. Calculations for the transition states by
      the DFT method support the predominant formation of the azetidine. The
      electroreduction of an aromatic imino ester prepared from (S)-aspartic acid gave
      almost equal amounts of a diastereomerically pure mixed ketal of cis-2,4
      disubstituted azetidine-3-one and a diastereomeric mixture of 2,5-disubstituted
      pyrollidine-3-one.

PMID- 16562883
TI  - Structurally well-defined, recoverable C3-symmetric tris(beta-hydroxy
      phosphoramide)-catalyzed enantioselective borane reduction of ketones.
AB  - [reaction: see text] A series of new chiral C(3)-symmetric tris(beta-hydroxy
      phosphoramide) ligands have been synthesized via the reaction of
      trisphosphoramide ester and Grignard reagents. The catalytic asymmetric borane
      reduction of ketones with these new C(3)-symmetric chiral tris(beta-hydroxy
      phosphoramide)s was investigated. Structurally well-defined, recoverable ligand
      1d is an efficient catalyst for the enantioselective borane reduction of both
      electron-deficient and electron-rich ketones, and high enantioselectivities were
      achieved (up to 98% ee).

PMID- 16562884
TI  - Phosphoric acids as amplifiers of molecular chirality in liquid crystalline
      media.
AB  - [structure: see text] A new system for the double amplification of the molecular
      chirality of simple chiral amines in achiral liquid crystalline media is
      described. It involves a conformationally flexible phosphoric acid based receptor
      that by binding to chiral amines induces chirality in the liquid crystalline
      matrix. Efficient cholesteric phase formation was shown by several chiral amines
      that were not able to induce measurable helicity in nematic liquid crystals by
      themselves.

PMID- 16562885
TI  - Short synthesis of octosyl nucleosides.
AB  - [reaction: see text] Commercial 1,2:5,6-di-O-isopropylidene-alpha-d-allofuranose
      was converted to a protected bicyclic octosyl acid thioglycoside donor by a 10
      step sequence that features an intramolecular ester enolate alkylation.
      Glycosylation of N-benzoyladenine and methyl uridine-5-carboxylate followed by
      deprotection gave the respective nucleosides "octosyl adenine" and octosyl acid
      A.

PMID- 16562886
TI  - Highly efficient construction of benzene ring in carbazoles by palladium
      catalyzed endo-mode oxidative cyclization of 3-(3'-alkenyl)indoles.
AB  - [reaction: see text] A highly efficient construction of the benzene ring in
      carbazoles by palladium-catalyzed endo-mode oxidative cyclization of 3-(3'
      alkenyl)indoles was developed. The reaction utilizes benzoquinone as the
      stoichiometric oxidant and is conducted under mild conditions.

PMID- 16562887
TI  - Rh-catalyzed enantioselective [2 + 2] cycloaddition of alkynyl esters and
      norbornene derivatives.
AB  - [reaction: see text] The enantioselective [2 + 2] cycloaddition of alkynes
      possessing an ester functionality and norbornene derivatives proceeded
      efficiently using a chiral rhodium catalyst. The chiral tri- and tetracyclic
      cyclobutenes were obtained in moderate to high ee.

PMID- 16562888
TI  - A facile access to N-sulfonylimidates and their synthetic utility for the
      transformation to amidines and amides.
AB  - [reaction: see text] It is shown that N-sulfonylimidates can be efficiently
      prepared by a three-component coupling of terminal alkynes, sulfonyl azides, and
      alcohols with use of a copper catalyst and an amine base. The reaction is
      characterized by mild conditions, high selectivity, and tolerance with various
      functional groups. Facile transformation of imidates to amidines was also
      achieved by sodium cyanide. Additionally, a protocol for the extremely efficient
      Pd-catalyzed [3,3]-sigmatropic rearrangement of allylic sulfonimidates to N
      allylic sulfonamides has been developed.

PMID- 16562889
TI  - Benzotetramisole: a remarkably enantioselective acyl transfer catalyst.
AB  - [reaction: see text] A commercially available pharmaceutical, tetramisole, was
      found to be a competent enantioselective acylation catalyst. Its benzannellated
      analogue, benzotetramisole (BTM), produced outstanding enantioselectivities in
      kinetic resolution of secondary benzylic alcohols.

PMID- 16562890
TI  - [60]Fullerene-fused lactones: manganese(III) acetate-mediated synthesis and novel
      reductive ring opening.
AB  - [reaction: see text] [60]Fullerene-fused lactones were prepared by the
      manganese(III) acetate-mediated reactions of [60]fullerene with carboxylic acids,
      carboxylic anhydrides, or malonic acids. Novel reductive ring opening of the
      lactones with Grignard reagents was observed.

PMID- 16562891
TI  - A practical chiral bicyclic thioglycolate lactam auxiliary for stereoselective
      quaternary carbon formation.
AB  - [reaction: see text] Chiral bicyclic thioglycolate lactams may be prepared in
      three steps from inexpensive commercial materials. The resulting lactams may be
      alkylated three times, twice using basic enolization and once using reductive
      enolization, to form alpha-quaternary carboxylic acid derivatives in high yield
      and with high diastereoselectivity. The alkylation products may be cleaved under
      either acidic or reductive conditions to furnish either carboxylic acids or
      primary alcohols, respectively.

PMID- 16562892
TI  - Novel h-shaped persistent architecture based on a dispiro building block system.
AB  - [structure: see text] A novel dispiro building block, dispiro[fluorene-9,5'(7'H)
      diindeno[2,1-b:1',2'-d]thiophene-7',9' '-fluorene], and its two derivatives, TBP
      DSFDITF and TDOF-DSFDITF, were designed and synthesized. Because of the rigidity
      and orthogonality of the spiro structure, TBP-DSFDITF exhibits a well-defined H
      shaped architecture, which consists of two ter(biphenyls) as the arms of the H
      shape and 3,4-diphenylthiophene as the rung, connecting via completely rigid
      dispiro linkages with two sp(3) carbon atoms.

PMID- 16562893
TI  - From small building blocks to complex molecular architecture.
AB  - [reaction: see text] We describe a synthesis of a dendrimer-like amphiphile
      containing a flat rigid core and 12 hydrophobic and hydrophilic arms. We employ a
      modular approach based on stepwise protection chemistry starting from simple
      building blocks. The key feature of this approach is the absence of a
      polymerization step, which makes it applicable for linear monofunctionalized
      precursors of any kind. This strategy also allows for precise control of the
      number of arms and ensures their alternating arrangement.

PMID- 16562894
TI  - Organogels derived from tetranitrated crown ethers.
AB  - [reaction: see text] The 3,3',4'4'-tetranitrodibenzocrown ethers TNDB24C8 and
      TNDB30C10 form organogels with chloroalkanes at 3% w/v. Atomic force microscopy
      and scanning electron microscopy have been used to characterize the
      superstructure of the gels. Gels prepared using TNDB30C10 and CHCl(3) are more
      fibrous and are ordered into elongated domains attributable to exposed parts of
      intermingled fibers. Differential scanning calorimetry shows that the gel aids in
      the formation of supercooled CHCl(3) (DeltaT = 21 K, DeltaH(av) = 19.0 +/- 1.5 kJ
      mol(-)(1)) and that the gel liquefies at 307 K.

PMID- 16562895
TI  - A solid-phase self-organized catalyst of nanopalladium with main-chain viologen
      polymers: alpha-alkylation of ketones with primary alcohols.
AB  - [reaction: see text] A novel solid-phase self-organized catalyst of palladium
      nanoparticles was prepared from PdCl(2) with main-chain viologen polymers via
      complexation and reduction. This insoluble nanocatalyst nano-Pd-V efficiently
      promoted alpha-alkylation of ketones with primary alcohols in the presence of
      Ba(OH)(2).H(2)O under atmospheric conditions without organic solvents. The nano
      Pd-V catalyst was reused without loss of catalytic activity.

PMID- 16562896
TI  - Solvent-controlled asymmetric Strecker reaction: stereoselective synthesis of
      alpha-trifluoromethylated alpha-amino acids.
AB  - [reaction: see text] Stereoselective approaches to alpha-trifluoromethylated
      alpha-amino acids (alpha-Tfm AAs) have been developed. The stereoconfigurations
      of the resulting alpha-Tfm AA precursors were well controlled by using different
      solvents. The optically active (S)-2-amino-2-phenyl-1,1,1-trifluoropropanoic acid
      was synthesized by this method.

PMID- 16562898
TI  - Facile synthesis of highly efficient phenyltetraene-based nonlinear optical
      chromophores for electrooptics.
AB  - [reaction: see text] A facile synthetic route has been developed to convert an
      electron-rich, sterically hindered dialkylaminodienone into a conjugated
      dialkylaminotrienal with good yield. The derived dialkylaminotetraene-type
      nonlinear optical chromophores possess an all-trans conformation and can be
      functionalized with fluoro-dendron to provide proper shape modification for
      poling. Polymers doped with two examples of these chromophores in high
      concentrations have been poled to afford ultra-large electrooptic coefficients
      (r(33)) of 208 and 262 pm/V, respectively, at the measuring wavelength of 1.31
      mum.

PMID- 16562897
TI  - Effective acceleration of atom transfer carbonylation of alkyl iodides by metal
      complexes. Application to the synthesis of the hinokinin precursor and
      dihydrocapsaicin.
AB  - [reaction: see text] Atom transfer carbonylation (ATC) of alkyl iodides leading
      to carboxylic acid esters is effectively accelerated by Pd(PPh(3))(4) and
      Mn(2)(CO)(10) under photoirradiation conditions. In the presence of amines, Pd(0)
      complexes affected double carbonylations leading to alpha-keto amides, whereas
      Mn(2)(CO)(10) accelerated only a single carbonylation reaction leading to the
      corresponding amides. The Pd(0)-accelerated ATC system was successfully applied
      to the synthesis of hinokinin and dihydrocapsaicin.

PMID- 16562899
TI  - Enantioselective organocatalytic Michael addition reactions between N
      heterocycles and nitroolefins.
AB  - [reaction: see text] A method for Michael addition of N-heterocycles to
      nitroolefins has been developed. The process is promoted by a cinchona alkaloid
      derivative to give Michael adducts in moderate to high enantioselectivities.

PMID- 16562900
TI  - Total synthesis of enantiopure (+)-gamma-lycorane using highly efficient Pd
      catalyzed asymmetric allylic alkylation.
AB  - [reaction: see text] A highly efficient short total synthesis of (+)-gamma
      lycorane (>99% ee, 41% overall yield) was achieved by using the asymmetric
      allylic alkylation in the key step catalyzed by palladium complexes with novel
      chiral biphenol-based monodentate phosphoramidite ligands.

PMID- 16562901
TI  - Stereochemical inversion in the vinylic substitution of boronic esters to give
      iodonium salts: participation of the internal oxy group.
AB  - [reaction: see text] Alkenylboronic esters having an acyloxy, alkoxy, or
      methoxycarbonyl group were employed for the reaction with (diacetoxyiodo)benzene
      in the presence of BF(3).OEt(2) to provide the alkenyliodonium tetrafluoroborates
      with inversion of configuration: (E)- and (Z)-boronates give (Z)- and (E)
      iodonium salts, respectively. This selectivity can be reversed by the addition of
      ether to the dichloromethane solution. The stereoselectivity can be explained by
      participation of the neighboring oxy group.

PMID- 16562902
TI  - Palladium-catalyzed cross-coupling reaction of triorganoindium reagents with
      propargylic esters.
AB  - [reaction: see text] Triorganoindium reagents (R(3)In) react with propargylic
      esters under palladium catalysis via an S(N)2' rearrangement to afford allenes in
      good yields and with high regioselectivity. The reaction proceeds smoothly at
      room temperature with a variety of R(3)In (aryl, alkenyl, alkynyl, and methyl).
      When chiral, nonracemic propargylic esters are employed, the reaction takes place
      with high anti-stereoselectivity providing allenes with high enantiomeric excess.

PMID- 16562903
TI  - One-pot borylation/amination reactions: syntheses of arylamine boronate esters
      from halogenated arenes.
AB  - [reaction: see text] A one-pot protocol for converting 1,3- and 1,4-substituted
      aryl halides to arylamine boronate esters is described. This is achieved by
      sequential Ir-catalyzed aromatic borylation at the least hindered C-H bond of the
      aryl halide and subsequent Pd-catalyzed C-N coupling at the halide position of
      the crude arylboronic ester.

PMID- 16562904
TI  - Aromatic borylation/amidation/oxidation: a rapid route to 5-substituted 3
      amidophenols.
AB  - [reaction: see text] 5-Substituted 3-amidophenols are prepared by subjecting 3
      substituted halobenzenes to an Ir-catalyzed aromatic borylation, followed by a Pd
      catalyzed amidation, and finally an oxidation of the boronic ester intermediate.
      The entire C-H activation borylation/amidation/oxidation sequence can be
      accomplished without isolation of any intermediate arenes. Usefully, amide
      partners can include lactams, carbamates, and ureas.

PMID- 16562905
TI  - Modulation of physical properties of Ter(9,9-ditolylfluorene) by backbone
      embedded heteroarenes.
AB  - [structure: see text] Novel ter(9,9-ditolylfluorene) analogues containing
      thiophene and pyridine rings embedded as functional constituents within the
      parent hydrocarbon backbone have been synthesized. These new molecules exhibit
      highly efficient photoluminescence and high thermal and morphological stability.
      The electronic structure of the terfluorene backbone is significantly perturbed,
      which allows modulation of the backbone energy levels.

PMID- 16562906
TI  - Sequential Pd- and Rh-catalyzed three-component cyclization with allenylboronate
      platform.
AB  - [reaction: see text] A novel three-component cyclization using allenylboronate
      ester is described. A three-component assembly of allenylboronate ester, aryl
      iodides, and stabilized carbon nucleophiles took place in the presence of
      palladium catalyst, furnishing functionalized alkenylboronate esters with high
      regio- and stereoselectivity. A Rh-catalyzed cyclization of the resultant three
      component products then afforded interesting carbocyclic frameworks efficiently.

PMID- 16562907
TI  - A tuneable self-complexing molecular switch.
AB  - [reaction: see text] A new self-complexing donor-acceptor system has been
      synthesized that has the propensity to undergo intramolecular decomplexation
      under thermal and electrochemical perturbation and upon addition of a competitive
      guest for the cyclophane's cavity.

PMID- 16562908
TI  - Total synthesis of (-)-xyloketal A.
AB  - [reaction: see text] The first total synthesis of the C(3)-symmetric and
      biologically active natural product, (-)-xyloketal A, has been accomplished in
      one step from phloroglucinol (1,3,5-trihydroxybenzene) and (4R)-3-hydroxymethyl
      2,4-dimethyl-4,5-dihydrofuran. This remarkably direct process involved an
      exceedingly facile and diastereoselective boron trifluoride diethyl etherate
      promoted triple electrophilic aromatic substitution reaction that was coupled to
      three bicyclic acetal formation reactions.

PMID- 16562909
TI  - 4,5,6,7-Tetrachlorobenzo[d][1,3,2]dioxaborol- 2-ol as an effective catalyst for
      the amide condensation of sterically demanding carboxylic acids.
AB  - [reaction: see text] 4,5,6,7-Tetrachlorobenzo[d][1,3,2]dioxaborole (4a) and
      4,5,6,7-tetrachlorobenzo[d][1,3,2]dioxaborol-2-ol (4b) are effective catalysts
      for the dehydrative amide condensation between an equimolar mixture of carboxylic
      acids and amines. In particular, these catalysts are greatly superior to 3,5
      bis(trifluoromethyl)phenylboronic acid (1) for the amide condensation of
      sterically demanding carboxylic acids. In contrast, 4c, which is prepared from a
      1:2 molar mixture of B(OH)(3) and tetrachlorocatechol, is effective as a Lewis
      acid-assisted Bronsted acid (LBA) catalyst for Ritter reaction.

PMID- 16562910
TI  - A versatile approach for the asymmetric syntheses of (1R,9aR)-epiquinamide and
      (1R,9aR)-homopumiliotoxin 223G.
AB  - [reaction: see text] Using 5b as a common intermediate, the first asymmetric
      synthesis of (-)-epiquinamide (4) and a formal asymmetric synthesis of (-)
      homopumiliotoxin 223G (2) is described. A key feature of our approach is the
      flexible introduction of a functionalized C(4) side chain to (S)-3
      benzyloxyglutarimide 7 in a regio- and diastereoselective manner. Utilization of
      a tandem Swern oxidation-Grignard addition strategy efficiently prevented
      racemization. An unexpected NaN(3)-promoted methanesulfonic acid elimination
      yielded 17, a reaction which could be useful for the syntheses of 8
      dehydrodesmethylpumiliotoxins such as alkaloid 235C (3).

PMID- 16562911
TI  - A highly practical instant catalyst for cyclotrimerization of alkynes to
      substituted benzenes.
AB  - [reaction: see text] A 2-(2,6-diisopropylphenyl)iminomethylpyridine
      (1a)/CoCl(2).6H(2)O/Zn reagent has been developed as an effective instant
      catalyst for the intra- and intermolecular cyclotrimerization of alkynes to
      substituted benzenes, making the method extremely practical since the reagent,
      1a/CoCl(2).6H(2)O/Zn, is inexpensive and easy to handle and the reaction is less
      sensitive to moisture and is reasonably general.

PMID- 16562912
TI  - Total synthesis of ageladine A, an angiogenesis inhibitor from the marine sponge
      Agelas nakamurai.
AB  - [reaction: see text] A 12-step total synthesis of the tricyclic heteroaromatic
      marine metabolite ageladine A has been achieved using a 6pi-azaelectrocyclization
      and a Suzuki-Miyaura coupling of N-Boc-pyrrole-2-boronic acid with a
      chloropyridine as key steps.

PMID- 16562913
TI  - Alpha-heteroarylation of esters, lactones, amides, and lactams by nucleophilic
      aromatic substitution.
AB  - [reaction: see text] A mild and efficient alpha-heteroarylation of simple esters
      and amides was developed via nucleophilic aromatic substitution. The choice of
      NaHMDS in toluene gave the best results. A tandem alpha-heteroarylation and
      hydroxylation protocol using air as the oxidant afforded tertiary alcohols in
      good yields.

PMID- 16562914
TI  - New nitronate sigma complexes and the mechanism of nucleophilic aromatic
      photosubstitution para to a nitro group.
AB  - [reaction: see text] Photolysis of 4-nitroanisole with aliphatic amines gives
      mainly N-substituted 4-nitroanilines. Reactions of this type have been widely
      attributed to a geminate radical mechanism. We questioned this interpretation and
      have searched for and found by NMR spectroscopy a new class of stable nitronate
      adducts generated under the reaction conditions. The adducts imply that
      photosubstitution by amines para to the nitro group occurs by meta sigma complex
      formation followed by an unprecedented sigmatropic rearrangement.

PMID- 16562915
TI  - Design and synthesis of 5'-deoxy-5'-phenyladenophostin A, a highly potent IP3
      receptor ligand.
AB  - [structure: see text] 5'-Deoxy-5'-phenyladenophostin A (5), designed as a useful
      IP(3) receptor ligand based on the previous structure-activity relationship
      studies, was successfully synthesized via two key stereoselective glycosidation
      steps. This compound proved to be a highly potent IP(3) receptor agonist.

PMID- 16562916
TI  - Origin of the diastereoselection in the indium-mediated addition of haloallylic
      sulfones to aldehydes.
AB  - [reaction: see text] The R(1) substituents at C(2) of the haloallylic sulfones 1
      play a pivotal role in controlling the diastereoselectivity of the indium
      mediated addition reaction to benzaldehyde to produce the homoallylic alcohols 3.
      The R(1) Me group of 1 prefers the chair form in the In-coordinated six-membered
      cyclic transition state to give anti-3a, and the R(1) Ph group of 1 favors the
      twist boat form to give syn-3n, both in a high 13:1 selectivity.

PMID- 16562917
TI  - Convergent synthesis of a polyfunctionalized fullerene by regioselective five
      fold addition of a functionalized organocopper reagent to C60.
AB  - [reaction: see text] A method for one-step preparation of polyfunctionalized
      fullerene derivatives by regioselective penta-addition of an organocopper reagent
      is described. A functionalized aryl iodide is first converted to the
      corresponding Grignard reagent and then to a copper reagent and finally is
      allowed to react with C(60). The method allows introduction of five functional
      groups to the C(60) skeleton in a convergent manner. The shuttlecock-like
      molecules crystallize into a columnar packing structure.

PMID- 16562918
TI  - On-water chemistry: copper-catalyzed straightforward synthesis of benzo[b]furan
      derivatives in neat water.
AB  - [reaction: see text] A more sustainable protocol leading to 2-alkyl- or 2-aryl
      substituted benzo[b]furans is reported, involving a copper-TMEDA complex which
      catalyzes the transformation of readily available ketone derivatives into the
      corresponding benzofurans in good to excellent yields. The reaction is
      accomplished using water as the solvent without organic cosolvents, and one
      example of catalyst reutilization is also presented.

PMID- 16562919
TI  - A supramolecular fluorescence probe for caffeine.
AB  - [structure: see text] Supramolecular sensing is rather limited to charged
      analytes. This report describes a practicable assay for caffeine, which employs a
      competitive "indicator-displacement" approach and allows detection by
      fluorescence. A simple analytical protocol is described that allows quantitation
      of caffeine in beverages.

PMID- 16562920
TI  - Sphenadilactones A and B, two novel nortriterpenoids from Schisandra
      sphenanthera.
AB  - [structure: see text] Two novel nortriterpenoid compounds, sphenadilactones A (1)
      and B (2), have been isolated from the leaves and stems of
      Schisandrasphenanthera. The structural elucidation of 1 and 2 was accomplished by
      extensive NMR analysis. The relative stereochemistry of 1 was established by
      single-crystal X-ray crystallography. Both compounds were tested for their
      cytotoxicities against K562, A549, and HT-29, and compound 1 was further tested
      for its anti-HIV-1 activity.

PMID- 16562921
TI  - Enantioselective rhodium-catalyzed addition of arylboronic acids to aldehydes
      using chiral spiro monophosphite ligands.
AB  - [reaction: see text] Highly efficient rhodium-catalyzed asymmetric addition of
      arylboronic acids to aldehydes has been realized by using chiral spiro
      monophosphite ligands, affording diarylmethanols in excellent yields and good
      enantiomeric excesses.

PMID- 16562922
TI  - Diastereospecific intramolecular Ullmann couplings: unique chiral auxiliary for
      the preparation of 3,3'-disubstituted MeO-BIPHEP derivatives.
AB  - [reaction: see text] A chiral auxiliary is described that provides only one
      diastereomer during intramolecular Ullmann couplings. Treatment of five Ullmann
      coupling precursors with Cu powder in DMF at 115 degrees C provides
      2,2',3,3',6,6'-hexasubstituted 1,1'-biphenyls as single diastereomers in yields
      ranging from 66% to 91%.

PMID- 16562923
TI  - Highly diastereoselective Diels-Alder reaction using a chiral auxiliary derived
      from levoglucosenone.
AB  - [reaction: see text] A new chiral auxiliary derived from levoglucosenone is
      reported. The compound is obtained by a cycloaddition reaction with 9-methoxy
      methylanthracene followed by a diastereoselective reduction of the C-2 keto
      function. The auxiliary has been used as a chiral template in an asymmetric Diels
      Alder reaction of the corresponding acrylic ester derivative with
      cyclopentadiene. The results showed excellent diastereomeric excess even at room
      temperature when the reaction was promoted by Et(2)AlCl as the Lewis acid.

PMID- 16562924
TI  - Synthesis of sterically hindered ortho-substituted tetraphenylethenes. Electronic
      effects in the McMurry olefination reaction.
AB  - [reaction: see text] Contrary to literature consensus, the McMurry olefination
      reaction can be extended to the direct synthesis of sterically encumbered
      tetrakis(2-substituted) tetraphenylethenes from the corresponding 2,2'
      disubstituted benzophenones. The reaction exploits previously unrecognized
      substrate-based electronic effects that dominate over otherwise controlling
      steric considerations and provides highly efficient access to derivatives of
      tetrakis(2-hydroxyphenyl)ethene, a novel preorganized ligand system for
      polymetallic coordination chemistry and catalysis.

PMID- 16562925
TI  - Preparation of pyrrolidine-based PDE4 inhibitors via enantioselective conjugate
      addition of alpha-substituted malonates to aromatic nitroalkenes.
AB  - [reaction: see text] The enantioselective conjugate addition of alpha-substituted
      malonates to aromatic nitroalkenes generates a stereocenter at the carbon bearing
      the aromatic group and an adjacent prochiral center from the alpha-substituted
      malonate. Nitro reduction followed by diastereoselective cyclization provides
      pyrrolidinones with two contiguous stereocenters, one of which is quaternary.
      This sequence was used for the preparation of the PDE4 inhibitor IC86518.
      Additional examples of the enantioselective Michael addition illustrate the scope
      of the reaction.

PMID- 16562926
TI  - Synthesis and functional properties of end-dendronized oligo(9,9
      diphenyl)fluorenes.
AB  - [structure: see text] A facile approach for the synthesis of a family of
      dendrimers OFn-EG with hole-transporting ability moieties by copper-catalyzed
      Buchwald's double-amination as a key reaction has been developed. These novel
      dendrimers exhibit good energy transfer efficiencies and very high thermal and
      electrochemical stabilities and have potential applications as hole transfer and
      emitting layers in the field of organic emitting diodes (OLEDs) or as host
      materials for electrophosphorescent applications.

PMID- 16562927
TI  - A facile and efficient direct aldol addition of simple thioesters.
AB  - [reaction: see text] Simple thioesters undergo direct aldol addition to aldehydes
      in the presence of MgBr(2).OEt(2) and i-Pr(2)NEt using untreated, reagent-grade
      CH(2)Cl(2) under atmospheric conditions. The reactions proceed extremely rapidly
      and in excellent yield.

PMID- 16562928
TI  - Total synthesis and biological evaluation of 11-desmethyllaulimalide, a highly
      potent simplified laulimalide analogue.
AB  - [reaction: see text] A step-economical synthesis of 11-desmethyllaulimalide (2)
      is reported. This simplified analogue is available through an improved second
      generation synthetic approach to the laulimalides, in a shorter step count and
      from much less expensive starting material than the parent compound. This new
      lead retains the anticancer function of laulimalide.

PMID- 16562930
TI  - Coarse and fine tuning of the electronic energies of triimineplatinum(II) square
      planar complexes.
AB  - [Pt(tbtrpy)X]Y complexes (tbtrpy = 4,4',4' '-tBu3-2,2';6',2' '-terpyridine)
      exhibit charge-transfer absorption bands that can be drastically red-shifted to
      long-wavelength visible absorptions with arylthiolates as X. Further extension to
      the near-IR (NIR) region is achieved with 7,7,8,8-tetracyanoquinodimethane (TCNQ
      ) as Y-, resulting in black absorbers with continuous UV-vis-NIR absorptions and
      opening up potential applications in energy research.

PMID- 16562931
TI  - Early metal di- and tricyanometalates: Useful building blocks for constructing
      magnetic clusters.
AB  - Treatment of mer-VCl3(THF)3 with KTp [Tp = hydridotris(3,5-dimethylpyrazol-1
      yl)borate], followed by [NEt4]CN in acetonitrile, affords
      [NEt4][(Tp)V(III)(CN)3].H2O (1.H2O); aerobic oxidation affords
      [NEt4][(Tp)V(IV)(O)(CN)2] (2). Subsequent treatment of 2 with Mn(II)(OTf)2 (OTf =
      trifluoromethanesulfonate) and 2,2'-bipyridine affords
      {[(Tp)V(O)(CN)2]2[Mn(II)(bipy)2]2[OTf]2}.2MeCN (3). Magnetic measurements
      indicate that 1-3 exhibit S = 1, (1/2), and 4 spin ground states, respectively.

PMID- 16562932
TI  - First metal azide complex with isonicotinate as a bridging ligand showing new net
      topology: hydrothermal synthesis, structure, and magnetic properties.
AB  - A new 3D azido-bridged coordination polymer, [Co1.5(N3)(OH)(Isonic)]n (1), has
      been synthesized and characterized and its magnetic properties studied.
      Isonicotinate acts as a bridging coligand in this complex. In 1, all of the
      ligands take tridentate bridging coordination modes, and the overall structure of
      1 exhibits a new 3,6-connected net topology.

PMID- 16562933
TI  - Phase transitions and second-harmonic generation in sodium monothiophosphate.
AB  - Oxythiophosphate compounds, which contain anions comprised of oxidized phosphorus
      bound to oxygen and sulfur, are scarce and, in general, poorly characterized.
      Although alpha-Na3PO3S has been known for over 60 years, little has been revealed
      about this compound. Here we present thermal analysis and second-harmonic
      generation (SHG) efficiency of alpha-Na3PO3S. Details about its transformation to
      the high-temperature beta phase are discussed. Under vacuum, alpha-Na3PO3S
      undergoes one endothermic event at 553 degrees C upon heating and two exothermic
      events at 504 and 467 degrees C upon cooling. beta-Na3PO3S can be trapped upon
      quenching Na3PO3S from high temperature. We have observed that the beta phase
      converts back to the alpha phase at room temperature. Interestingly, relative
      humidity has been determined to catalyze this phase transformation. alpha-Na3PO3S
      oxidizes at 315 degrees C in air to produce Na4P2O7 and Na2SO4. Upon exposure to
      1064-nm incident radiation, noncentrosymmetric alpha-Na3PO3S produces an SHG
      efficiency 200 times that of alpha-quartz and is nonphase-matchable (type 1).

PMID- 16562934
TI  - Two chain compounds of [M(N3)2(HCOO)][(CH3)2NH2] (M = Fe and Co) with a mixed
      azido/formato bridge displaying metamagnetic behavior.
AB  - Two new magnetic chain compounds, where the anionic [M(N3)2(HCOO)-]n chains with
      a 3-fold bridge of two end-on azido and one syn-syn formato ligands are isolated
      by the cations of [(CH3)2NH2]+, exhibit metamagnetism because of the strong
      intrachain ferromagnetic coupling versus the weak interchain antiferromagnetic
      coupling.

PMID- 16562935
TI  - [P6Se12]4-: a phosphorus-rich selenophosphate with low-valent P centers.
AB  - The new selenophosphate Rb4P6Se12 features the trans-decalin-like, [P6Se12]4-
      anion, a phosphorus-rich species that possesses three parallel P-P bonds and
      formally P2+ and P4+ centers. The synthesis of Rb4P6Se12 was accomplished with
      the reductive addition of P to RbPSe6 and represents an interesting example of
      how alkali chalcophosphates can serve as starting materials to produce new
      compounds under mild reaction conditions.

PMID- 16562936
TI  - Synthesis, structures, and luminescent properties of phenol-pyridyl boron
      complexes.
AB  - Syntheses of the four mixed phenol-pyridine derivatives 1,6-bis(2
      hydroxyphenyl)pyridyl boron naphthalene (1), 1,6-bis(2-hydroxy-5
      methylphenyl)pyridyl boron naphthalene (2), 1,6-bis(2-hydroxyphenyl)pyridyl boron
      2-methoxylbenzene (3), and 1,6-bis(2-hydroxy-5-methylphenyl)pyridyl boron 2
      methoxylbenzene (4) are reported. The structures of the boron compounds 1, 3, and
      4 were determined by single-crystal X-ray diffraction. The molecular packing is
      characterized by intermolecular pi...pi and hydrogen-bonding interactions. DSC
      analysis demonstrates that 1 and 2 have good thermal stability with higher glass
      transition temperatures (Tg) and melting points (Tm) than 3 and 4. Boron
      complexes 1-4 display bright blue luminescence in solution and the solid state.
      White and blue electroluminescent (EL) devices were fabricated successfully using
      these boron compounds.

PMID- 16562937
TI  - Spectroscopic properties and electronic structure of five- and six-coordinate
      iron(II) porphyrin NO complexes: Effect of the axial N-donor ligand.
AB  - In this paper, the differences in the spectroscopic properties and electronic
      structures of five- and six-coordinate iron(II) porphyrin NO complexes are
      explored using [Fe(TPP)(NO)] (1; TPP = tetraphenylporphyrin) and
      [Fe(TPP)(MI)(NO)] (2; MI = 1-methylimidazole) type systems. Binding of N-donor
      ligands in axial position trans to NO to five-coordinate complexes of type 1 is
      investigated using UV-vis absorption and 1H NMR spectroscopies. This way, the
      corresponding binding constants Keq are determined and the 1H NMR spectra of 1
      and 2 are assigned for the first time. In addition, 1H NMR allows for the
      determination of the degree of denitrosylation in solutions of 1 with excess
      base. The influence of the axial ligand on the properties of the coordinated NO
      is then investigated. Vibrational spectra (IR and Raman) of 1 and 2 are presented
      and assigned using isotope substitution and normal-coordinate analysis. Obtained
      force constants are 12.53 (N-O) and 2.98 mdyn/A (Fe-NO) for 1 compared to 11.55
      (N-O) and 2.55 mdyn/A (Fe-NO) for 2. Together with the NMR results, this provides
      experimental evidence that binding of the trans ligand weakens the Fe-NO bond.
      The principal bonding schemes of 1 and 2 are very similar. In both cases, the Fe
      N-O subunit is strongly bent. Donation from the singly occupied pi* orbital of NO
      into d(z2) of iron(II) leads to the formation of an Fe-NO sigma bond. In
      addition, a medium-strong pi back-bond is present in these complexes. The most
      important difference in the electronic structures of 1 and 2 occurs for the Fe-NO
      sigma bond, which is distinctively stronger for 1 in agreement with the
      experimental force constants. The increased sigma donation from NO in 1 also
      leads to a significant transfer of spin density from NO to iron, as has been
      shown by magnetic circular dichroism (MCD) spectroscopy in a preceding
      Communication (Praneeth, V. K. K.; Neese, F.; Lehnert, N. Inorg. Chem. 2005, 44,
      2570-2572). This is confirmed by the 1H NMR results presented here. Hence,
      further experimental and computational evidence is provided that complex 1 has
      noticeable Fe(I)NO+ character relative to 2, which is an Fe(II)NO(radical)
      complex. Finally, using MCD theory and quantum chemical calculations, the
      absorption and MCD C-term spectra of 1 and 2 are assigned for the first time.

PMID- 16562938
TI  - Solution and solid-state properties of luminescent M-M bond-containing
      coordination/organometallic polymers using the RNC-M2(dppm)2-CNR building blocks
      (M = Pd, Pt; R = Aryl, Alkyl).
AB  - Two families of organometallic polymers built upon the bimetallic M2(dppm)2L(2)2+
      fragments (M = Pd, Pt; dppm = bis(diphenylphosphino)methane, L = 1,4-diisocyano
      2,3,5,6-tetramethylbenzene (diiso), 1,8-diisocyano-p-menthane (dmb), 1-isocyano
      2,6-dimethylbenzene, 1-isocyano-4-isopropylbenzene, and tert-butylisocyanide)
      were synthesized and fully characterized (1H and 31P NMR, X-ray crystallography
      (model compounds), IR, Raman, chem. anal., TGA, DSC, powder XRD, 31P NMR T1 and
      NOE, light scattering, and conductivity measurements). Evidence for polymers in
      the solid state is provided from the swelling of the polymers upon dissolution
      and the formation of stand-alone films. However, these species become small
      oligomers when dissolved. The materials are luminescent in the solid state at 298
      and 77 K and in PrCN solution at 77 K. These emissions result from triplet 3(d
      sigma d sigma*) states despite the presence of low-lying pi-pi* MO levels
      according to DFT calculations for the aryl isocyanide model compounds. The
      emission band maxima are located between 640 and 750 nm and exhibit lifetimes of
      3-6 ns for the Pd species and 3-4 micros for the Pt analogues in PrCN solution at
      77 K. No evidence of intramolecular excitonic photoprocesses was found in any of
      the polymers.

PMID- 16562939
TI  - Oscillatory reactions involving hydrogen peroxide and thiosulfate-kinetics of the
      oxidation of tetrathionate by hydrogen peroxide.
AB  - The reaction between tetrathionate and hydrogen peroxide forms an important part
      of several pH oscillators based on the oxidation of thiosulfate. The kinetics of
      this reaction were examined in a batch reactor by measurement of the initial pH
      values in the range from 8 to 10.5. Experimental data were evaluated by the
      method of initial reaction rates combined with the assumption of instantaneously
      equilibrated acid-base reactions. The rate-determining step was found to be of
      the first order with respect to tetrathionate, hydrogen peroxide, and OH- ions
      with the value of rate constant k = (1.50 +/- 0.03) x 10(2) (M2 s)(-1) at 25
      degrees C. In the alkaline solution, no distinct catalytic effect of Cu2+ was
      observed in contrast to earlier assumptions. The waveform of measured pH over the
      course of the reaction indicates that thiosulfate is probably an intermediate
      because characteristics of the curves are very similar to those for the oxidation
      of thiosulfate. We also measured the time evolution of concentrations of major
      components by the attenuated total internal reflectance infrared spectroscopy to
      further elucidate the underlying reaction mechanism. These measurements confirm
      the suspected role of thiosulfate as an intermediate in the studied reaction and
      provide valuable detailed information on the time evolution of thiosulfate,
      sulfite, sulfate, tetrathionate, and trithionate. These experimental observations
      are included in a simple mechanism that accurately simulates the reaction course
      in an alkaline solution. The results provide considerable new insights into the
      nature of autocatalysis in the hydrogen peroxide-thiosulfate-Cu2+ reaction and
      suggest that a new role for Cu2+ in the oscillatory dynamics observed in a flow
      through reactor needs to be found.

PMID- 16562940
TI  - Quantum chemistry-based analysis of the vibrational spectra of five-coordinate
      metalloporphyrins [M(TPP)Cl].
AB  - Vibrational properties of the five-coordinate porphyrin complexes [M(TPP)(Cl)] (M
      = Fe, Mn, Co) are analyzed in detail. For [Fe(TPP)(Cl)] (1), a complete
      vibrational data set is obtained, including nonresonance (NR) Raman, and
      resonance Raman (RR) spectra at multiple excitation wavelengths as well as IR
      spectra. These data are completely assigned using density functional (DFT)
      calculations and polarization measurements. Compared to earlier works, a number
      of bands are reassigned in this one. These include the important, structure
      sensitive band at 390 cm(-1), which is reassigned here to the totally symmetric
      nu(breathing)(Fe-N) vibration for complex 1. This is in agreement with the
      assignments for [Ni(TPP)]. In general, the assignments are on the basis of an
      idealized [M(TPP)]+ core with D(4h) symmetry. In this Work, small deviations from
      D(4h) are observed in the vibrational spectra and analyzed in detail. On the
      basis of the assignments of the vibrational spectra of 1, [Mn(TPP)(Cl)] (2), and
      diamagnetic [Co(TPP)(Cl)] (3), eight metal-sensitive bands are identified. Two of
      them correspond to the nu(M-N) stretching modes with B(1g) and Eu symmetries and
      are assigned here for the first time. The shifts of the metal sensitive modes are
      interpreted on the basis of differences in the porphyrin C-C, C-N, and M-N
      distances. Besides the porphyrin core vibrations, the M-Cl stretching modes also
      show strong metal sensitivity. The strength of the M-Cl bond in 1-3 is further
      investigated. From normal coordinate analysis (NCA), force constants of 1.796
      (Fe), 0.932 (Mn), and 1.717 (Co) mdyn/A are obtained for 1-3, respectively. The
      weakness of the Mn-Cl bond is attributed to the fact that it only corresponds to
      half a sigma bond. Finally, RR spectroscopy is used to gain detailed insight into
      the nature of the electronically excited states. This relates to the mechanism of
      resonance enhancement and the actual nature of the enhanced vibrations. It is of
      importance that anomalous polarized bands (A(2g) vibrations), which are
      diagnostic for vibronic mixing, are especially useful for this purpose.

PMID- 16562941
TI  - Structures, photoluminescence, up-conversion, and magnetism of 2D and 3D rare
      earth coordination polymers with multicarboxylate linkages.
AB  - Four new rare-earth compounds, [Eu(NDC)1.5(DMF)2] (1), [Nd2(NDC)3(DMF)4].H2O (2),
      [La2(NDC)3(DMF)4].0.5H2O (3), and [Eu(BTC)(H2O)] (4), where NDC = 1,4
      naphthalenedicarboxylate, BTC = 1,3,5-benzenetricarboxylate, and DMF = N,N
      dimethylformamide, have been synthesized through preheating and cooling-down
      crystallization. Compounds 1-3 possess similar 2D structures, in which the NDC
      ligands link M(III) (M = La, Nd, and Eu) ions of two adjacent double chains
      constructed by NDC ligands and dinuclear M(III) building units. In compound 4,
      the Eu(III) ion is seven-coordinated by O atoms from six BTC ligands and one
      terminal water molecule in a distorted pentagonal-bipyramidal coordination
      environment. If the BTC ligand and the Eu(III) ion are regarded as six-connected
      nodes, respectively, the structure of compound 4 can be well described as a 3D
      six-connected net. Furthermore, compounds 1 and 4 exhibit strong red luminescence
      upon 355-nm excitation. Compound 2 displays interesting emissions in the near-IR
      region, and yellow (580 nm) pumping of this compound results in UV and intense
      blue emissions through an up-conversion process. The magnetic properties of
      compounds 1, 2, and 4 have been studied through measurement of their magnetic
      susceptibilities over the temperature range of 4-300 K.

PMID- 16562942
TI  - STM/STS observation of polyoxoanions on HOPG surfaces: the wheel-shaped
      [Cu20Cl(OH)24(H2O)12(P8W48O184)]25- and the ball-shaped
      [{Sn(CH3)2(H2O)}24{Sn(CH3)2}12(A-PW9O34)12]36-.
AB  - A combination of scanning tunneling microscopy (STM) and scanning tunneling
      spectroscopy (STS) techniques have been performed on the wheel-shaped
      [Cu20Cl(OH)24(H2O)12(P8W48O184)]25- and the ball-shaped
      [{Sn(CH3)2(H2O)}24{Sn(CH3)2}12(A-PW9O34)12]36- deposited on highly oriented
      pyrolytic graphite surfaces. Small, regular molecule clusters, as well as
      separated single molecules, were observed. The size of the molecules is in
      agreement with the data determined by X-ray crystallography. In STS measurements,
      we found a rather large contrast at the expected location of the Cu metal centers
      in our molecules, i.e., the location of the individual Cu ions in their organic
      matrix is directly addressable by STS.

PMID- 16562943
TI  - Sequential reaction intermediates in aliphatic C-H bond functionalization
      initiated by a bis(mu-oxo)dinickel(III) complex.
AB  - The reaction of [Ni2(OH)2(Me2-tpa)2]2+ (1) (Me2-tpa = bis(6-methyl-2
      pyridylmethyl)(2-pyridylmethyl)amine) with H2O2 causes oxidation of a methylene
      group on the Me2-tpa ligand to give an N-dealkylated ligand and oxidation of a
      methyl group to afford a ligand-based carboxylate and an alkoxide as the final
      oxidation products. A series of sequential reaction intermediates produced in the
      oxidation pathways, a bis(mu-oxo)dinickel(III) ([Ni2(O)2(Me2-tpa)2]2+ (2)), a
      bis(mu-superoxo)dinickel(II) ([Ni2(O2)2(Me2-tpa)2]2+ (3)), a (mu-hydroxo)(mu
      alkylperoxo)dinickel(II) ([Ni2(OH)(Me2-tpa)(Me-tpa-CH2OO)]2+ (4)), and a bis(mu
      alkylperoxo)dinickel(II) ([Ni2(Me-tpa-CH2OO)2]2+ (5)), was isolated and
      characterized by various physicochemical measurements including X-ray
      crystallography, and their oxidation pathways were investigated. Reaction of 1
      with H2O2 in methanol at -40 degrees C generates 2, which is extremely reactive
      with H2O2, producing 3. Complex 2 was isolated only from disproportionation of
      the superoxo ligands in 3 in the absence of H2O2 at -40 degrees C. Thermal
      decomposition of 2 under N2 generated an N-dealkylated ligand Me-dpa ((6-methyl-2
      pyridylmethyl)(2-pyridylmethyl)amine) and a ligand-coupling dimer (Me-tpa-CH2)2.
      The formation of (Me-tpa-CH2)2 suggests that a ligand-based radical Me-tpa-CH2*
      is generated as a reaction intermediate, probably produced by H-atom abstraction
      by the oxo group. An isotope-labeling experiment revealed that intramolecular
      coupling occurs for the formation of the coupling dimer. The results indicate
      that the rebound of oxygen to Me-tpa-CH2* is slower than that observed for
      various high-valence bis(mu-oxo)dimetal complexes. In contrast, the decomposition
      of 2 and 3 in the presence of O2 gave carboxylate and alkoxide ligands,
      respectively (Me-tpa-COO- and Me-tpa-CH2O-), instead of (Me-tpa-CH2)2, indicating
      that the reaction of Me-tpa-CH2* with O2 is faster than the coupling of Me-tpa
      CH2* to generate ligand-based peroxyl radical Me-tpa-CH2OO*. Although there is a
      possibility that the Me-tpa-CH2OO* species could undergo various reactions, one
      of the possible reactive intermediates, 4, was isolated from the decomposition of
      3 under O2 at -20 degrees C. The alkylperoxo ligands in 4 and 5 can be converted
      to a ligand-based aldehyde by either homolysis or heterolysis of the O-O bond,
      and disproportionation of the aldehyde gives a carboxylate and an alkoxide via
      the Cannizzaro reaction.

PMID- 16562944
TI  - Controlling aggregation of copper(II)-based coordination compounds: From
      mononuclear to dinuclear, tetranuclear, and polymeric copper complexes.
AB  - The use of a strategy combining ligand design and changes of reaction conditions
      has been investigated with the goal of directing the assembly of mononuclear,
      dinuclear, tetranuclear, and polymeric copper(II) complexes. As a result, closely
      related copper monomers, alkoxo dimers, and hydroxo cubanes, along with a
      carbonate-bridged polymeric species, have been synthesized using the rigid,
      aliphatic amino ligands cis-3,5-diamino-trans-hydroxycyclohexane (DAHC), cis-3,5
      diamino-trans-methoxycyclohexane (DAMC), and the glutaryl-linked derivative
      glutaric acid bis-(cis-3,5-diaminocyclohexyl) ester (GADACE). The composition of
      the monomeric complex has been determined by X-ray crystallography as
      [Cu(DAHC)2](ClO4)2 (1), the two dimers as [{Cu(DAHC)(OMe)}2](ClO4)2.MeOH (2) and
      [{Cu(DAMC)(OMe)(ClO4)}2] (3), the three Cu4O4 cubanes as
      [{Cu(DAHC)(OH)}4](ClO4)(4).2.5MeOH (4), [{Cu(DAMC)(OH)}4](ClO4)4.H2O (5), and
      [{Cu2(OH)2(GADACE)}2]Cl4.2MeOH.6H2O (6), and an infinite-chain structure as
      [{Cu(DAHC)(CO3)}n] (7). Furthermore, the cubane structures 4 and 5 have been
      investigated magnetically. Our studies indicate that formation of the monomeric,
      dimeric, and tetranuclear DAHC and DAMC complexes can be controlled by small
      changes in reaction conditions and that further preorganization of the ligand
      moiety by linking the DAHC cores (GADACE) allows more effective direction of the
      self-assembly of the Cu4O4 cubane core.

PMID- 16562945
TI  - Syntheses, structures, near-infrared and visible luminescence, and magnetic
      properties of lanthanide-organic frameworks with an imidazole-containing flexible
      ligand.
AB  - Reactions of tripodal ligand 1,3,5-tris(imidazole-1-ylmethyl)-2,4,6
      trimethylbenzene (L) with lanthanide metal salts and triethyl orthoformate led to
      the formation of six bowl-like dinuclear compounds
      [Ln2(L)(HL)(NO3)6(HCOO)].3CH3OH (Ln = Gd 1, Tb 2, Dy 3, Er 4, Yb 5, and Eu 6).
      The single-crystal X-ray diffraction analysis revealed that six complexes are
      isomorphous and isostructural and that the dinuclear molecules are further
      connected by hydrogen bonds and pi-pi interactions, resulting in 3D channel-like
      structures. The luminescence properties have been studied, and the results showed
      that the Tb(III) (2) and Eu(III) (6) complexes exhibited sensitized luminescence
      in the visible region and their luminescence lifetimes in powder and DMSO-d6
      solution are in the range of milliseconds. The Yb(III) complex (5) emits typical
      near-infrared luminescence in DMSO-d6 solution. Variable-temperature magnetic
      susceptibility measurements of 1-6 showed that complex 1 (Gd) is nearly a
      paramagnet and complexes 2 (Tb), 3 (Dy), and 4 (Er) show the ferromagnetic
      coupling between magnetic centers, whereas the depopulation of the Stark levels
      in complexes 5 (Yb) and 6 (Eu) leads to a continuous decrease in (chi M)T when
      the sample is cooled from 300 to 1.8 K.

PMID- 16562946
TI  - Electronic properties, redox behavior, and interactions with H2O2 of pH-sensitive
      hydroxyphenyl-1,2,4-triazole-based oxovanadium(V) complexes.
AB  - The syntheses and spectroscopic characterization of two 1,2,4-triazole-based
      oxovanadium(V) complexes are reported: 1- [VO2L1]- and 2 [(VOL2)2(OMe)2] (where
      H2L1 = 3-(2'-hydroxyphenyl)-5-(pyridin-2' '-yl)-1H-1,2,4-triazole, H3L2 = bis-3,5
      (2'-hydroxyphenyl)-1H-1,2,4-triazole). The ligand environment (N,N,O vs O,N,O) is
      found to have a profound influence on the properties and reactivity of the
      complexes formed. The presence of the triazolato ligand allows for pH tuning of
      the spectroscopic and electrochemical properties, as well as the interaction and
      stability of the complexes in the presence of hydrogen peroxide. The vanadium(IV)
      oxidation states were generated electrochemically and characterized by UV-vis and
      EPR spectroscopies. For 2, under acidic conditions, rapid exchange of the
      methoxide ligands with solvent [in particular, in the vanadium(IV) redox state]
      was observed.

PMID- 16562947
TI  - New oligophosphines and (hydroxymethyl)phosphonium chlorides.
AB  - The new oligophosphines [H2P(CH2)2]2PH, [H2P(CH2)2P(H)CH2]2,
      and{[(H2P(CH2)2]2PCH2}2 have been made by hydrophosphination of diethyl
      vinylphosphonate (2) with H2P(CH2)2PH2 (1), using different ratios of 2/1,
      followed by LiAlH4 reduction of the phosphonate intermediates; the three
      phosphonate precursors were obtained as oils of varying purity (approximately 90
      95%) in low (approximately 20%) to almost quantitative yield. The tri-, tetra-,
      and hexaphosphines were then treated with formaldehyde in the presence of
      hydrochloric acid to generate the corresponding water-soluble
      (hydroxymethyl)phosphonium chlorides
      {(HOCH2)3P[(CH2)2P(CH2OH)2]n(CH2)2P(CH2OH)3}Cl m (n = 1, m = 3; n = 2, m = 4) and
      {[(HOCH2)3P(CH2)2]2P(CH2OH)CH2}2Cl6 that were characterized by NMR spectroscopy
      and elemental analysis. The known (hydroxymethyl)bisphosphonium chloride
      [(HOCH2)3P(CH2)2]2Cl2 was similarly prepared from H2P(CH2)2PH2, and the
      determined crystal structure revealed strong hydrogen bonding between the
      chloride anions and the hydrogen atoms of the hydroxymethyl groups.

PMID- 16562948
TI  - Dinuclear copper(II) complexes with {Cu2(mu-hydroxo)bis(mu-carboxylato)}+ cores
      and their reactions with sugar phosphate esters: A substrate binding model of
      fructose-1,6-bisphosphatase.
AB  - Reactions of CuX2.nH2O with the biscarboxylate ligand XDK (H2XDK = m
      xylenediamine bis(Kemp's triacid imide)) in the presence of N-donor auxiliary
      ligands yielded a series of dicopper(II) complexes, [Cu2(mu-OH)(XDK)(L)2]X (L =
      N,N,N',N'-tetramethylethylenediamine (tetmen), X = NO3 (1a), Cl (1b); L = N,N,N'
      trimethylethylenediamine (tmen), X = NO3 (2a), Cl (2b); L =2,2'-bipyridine (bpy),
      X = NO3 (3); L = 1,10-phenanthroline (phen), X = NO3 (4); L = 4,4'-dimethyl-2,2'
      bipyridine (Me2bpy), X = NO3 (5); L = 4-methyl-1,10-phenanthroline (Mephen), X =
      NO3 (6)). Complexes 1-6 were characterized by X-ray crystallography (Cu...Cu =
      3.1624(6)-3.2910(4) A), and the electrochemical and magnetic properties were also
      examined. Complexes 3 and 4 readily reacted with diphenyl phosphoric acid (HDPP)
      or bis(4-nitrophenyl) phosphoric acid (HBNPP) to give [Cu2(mu
      phosphate)(XDK)(L)2]NO3 (L = bpy, phosphate = DPP (11); L = phen, phosphate = DPP
      (12), BNPP (13)), where the phsophate diester bridges the two copper ions in a mu
      1,3-O,O' bidentate fashion (Cu...Cu = 4.268(3)-4.315(1) A). Complexes 4 and 6
      with phen and Mephen have proven to be good precursors to accommodate a series of
      sugar monophosphate esters (Sugar-P) onto the biscarboxylate-bridged dicopper
      centers, yielding [Cu2(mu-Sugar-P)(XDK)(L)2] (Sugar-P = alpha-D-Glc-1-P (23a and
      b), D-Glc-6-P (24a and b), D-Man-6-P (25a), D-Fru-6-P (26a and b); L = phen (a),
      Mephen (b)) and [Cu2(mu-Gly-n-P)(XDK)(Mephen)2] (Gly-n-P = glycerol n-phosphate;
      n = 2 (21), 3 (22)), where Glc, Man, and Fru are glucose, mannose, and fructose,
      respectively. The structure of [Cu2(mu-MNPP)(XDK)(phen)2(CH3OH)] (20) was
      characterized as a reference compound (H2MNPP = 4-nitrophenyl phosphoric acid).
      Complexes 4 and 6 also reacted with d-fructose 1,6-bisphosphate (D-Fru-1,6-P2) to
      afford the tetranuclear copper(II) complexes formulated as [Cu4(mu-D-Fru-1,6
      P2)(XDK)2(L)4] (L = phen (27a), Mephen (27b)). The detailed structure of 27a was
      determined by X-ray crystallography to involve two different tetranuclear
      complexes with alpha- and beta-anomers of D-Fru-1,6-P2, [Cu4(mu-alpha-D-Fru-1,6
      P2)(XDK)2(phen)4] and [Cu4(mu-beta-D-Fru-1,6-P2)(XDK)2(phen)4], in which the D
      Fru-1,6-P2 tetravalent anion bridges the two [Cu2(XDK)(phen)2]2+ units through
      the C1 and C6 phosphate groups in a mu-1,3-O,O' bidentate fashion (Cu...Cu =
      4.042(2)-4.100(2) A). Notably, the structure with alpha-D-Fru-1,6-P2 demonstrated
      the presence of a strong hydrogen bond between the C2 hydroxyl group and the C1
      phosphate oxygen atom, which may support the previously proposed catalytic
      mechanism in the active site of fructose-1,6-bisphosphatase.

PMID- 16562949
TI  - Weak exchange interaction supported by a biologically relevant long chemical
      bridge in a Cu-peptide model compound.
AB  - The copper complex of the dipeptide L-alanyl-L-phenylalanine, catena-(L-alaninate
      L-phenylalaninate-copper(II) monohydrate), identified as Cu(II)Ala-Phe, provides
      a convenient system to study a weak exchange interaction between unpaired spins
      transmitted through a biologically relevant long chemical bridge (18.34 A). In
      this complex, the copper ions are arranged in two symmetry-related anisotropic
      layers parallel to the ab plane at 13.17 A, separated by a double layer of water
      molecules. The equatorial-equatorial bridge considered as the most relevant path
      for exchange interactions between copper ions in neighbor layers contains 11
      diamagnetic atoms (including three hydrogens), with two covalent amidate bridges
      plus three weak and moderate H bonds that go across the water layer. This
      interaction was studied using electron paramagnetic resonance in single-crystal
      samples, at 9.5 and 34.5 GHz. The measured magnitude of the interlayer
      interaction, |J3|/kB = 1.7(2) x 10(-3) K, is discussed in terms of values
      obtained for similar paths in other model compounds and in proteins. These
      results in model systems provide information that may be important in
      understanding biological functions at the molecular level.

PMID- 16562950
TI  - Thermodynamic and kinetic studies on reactions of Pt(II) complexes with
      biologically relevant nucleophiles.
AB  - The effect of different N-N spectator ligands on the reactivity of platinum(II)
      complexes was investigated by studying the water lability of
      [Pt(diaminocyclohexane)(H2O)2]2+ (Pt(dach)), [Pt(ethylenediamine)(H2O)2]2+
      (Pt(en)), [Pt(aminomethylpyridine)(H2O)2]2+ (Pt(amp)), and [Pt(N,N'
      bipyridine)(H2O)2]2+ (Pt(bpy)). Some of the selected N-N chelates form part of
      the coordination sphere of Pt(II) drugs in clinical use, as in Pt(dach)
      (oxaliplatin), or are models, regarding the nature of the amines, with higher
      stability in terms of substitution and hydrolysis of the diamine moiety, as in
      Pt(en) (cisplatin) and Pt(amp) (AMD473). The effect of pi-acceptors on the
      reactivity was investigated by introducing one (Pt(amp)) or two pyridine rings
      (Pt(bpy)) in the system. The pK(a) values for the two water molecules (viz.,
      Pt(dach) (pK(a1) = 6.01, pK(a2) = 7.69), Pt(en) (pK(a1) = 5.97, pK(a2) = 7.47),
      Pt(amp) (pK(a1) = 5.82, pK(a2) = 6.83), Pt(bpy) (pK(a1) = 4.80, pK(a2) = 6.32)
      show a decrease in the order Pt(dach) > Pt(en) > Pt(amp) > Pt(bpy). The
      substitution of both coordinated water molecules by a series of nucleophiles
      (viz., thiourea (tu), L-methionine (L-Met), and guanosine-5'-monophosphate (5'GMP
      ) was investigated under pseudo-first-order conditions as a function of
      concentration, temperature, and pressure using UV-vis spectrophotometric and
      stopped-flow techniques and was found to occur in two subsequent reaction steps.
      The following k1 values for Pt(dach), Pt(en), Pt(amp), and Pt(bpy) were found: tu
      (25 degrees C, M(-1) s(-1)) 21 +/- 1, 34.0 +/- 0.4, 233 +/- 5, 5081 +/- 275; L
      Met (25 degrees C) 0.85 +/- 0.01, 0.70 +/- 0.03, 2.15 +/- 0.05, 21.8 +/- 0.6;
      5'GMP- (40 degrees C) 5.8 +/- 0.2, 3.9 +/- 0.1, 12.5 +/- 0.5, 24.4 +/- 0.3. The
      results for k2 for Pt(dach), Pt(en), Pt(amp), and Pt(bpy) are as follows: tu (25
      degrees C, M(-1) s(-1)) 11.5 +/- 0.5, 10.2 +/- 0.2, 38 +/- 1, 1119 +/- 22; L-Met
      (25 degrees C, s(-1)) 2.5 +/- 0.1, 2.0 +/- 0.2, 1.2 +/- 0.3, 290 +/- 4; 5'GMP-
      (40 degrees C, M(-1) s(-1)) 0.21 +/- 0.02, 0.38 +/- 0.02, 0.97 +/- 0.02, 24 +/-
      1. The activation parameters for all reactions suggest an associative
      substitution mechanism. The pK(a) values and substitution rates of the complexes
      studied can be tuned through the nature of the N-N chelate, which is important in
      the development of new active compounds for cancer therapy.

PMID- 16562951
TI  - Electronic structures of KNa3In9 and Na2In, two metallic phases with classical
      closed-shell electronic configurations.
AB  - The cluster compounds KNa3In9 [K2Na6(In12)(In)6] and Na2In [(Na)8(In4)], which
      contain In12 icosahedra interbridged by 4-bonded In atoms and isolated In4
      tetrahedra, respectively, both have classical closed-shell electronic
      configurations but show metallic transport properties. These contrasts have been
      studied by means of first-principles density functional methods (LMTO-ASA).
      Several bands cross the Fermi level in both compounds, consistent with their
      metallic properties. In KNa3In9, the metal atom framework alone is sufficient to
      generate a metallic characteristic. The alkali-metal s and indium p orbitals mix
      considerably in both phases, providing for substantial covalent contributions to
      their stabilities as well as bands crossing Ef. The participation of Na atoms in
      the 3D bonding networks is more striking in cation-richer Na2In than in KNa3In9.

PMID- 16562952
TI  - Supramolecuar motifs in s-block metal-bound sulfonated monoazo dyes: The case of
      Orange G.
AB  - Solid-state structures of Mg, Sr, Ba, Na2, Na0.8K1.2, NaRb, and Na1.5Cs0.5
      complexes of the disulfonated dye 7-hydroxy-8-(phenylazo)-1,3
      naphthalenedisulfonic acid, Orange G, are presented. It is shown that the s-block
      metal salts of the Orange G dianion (Og) can be categorized into three structural
      classes related to those previously proposed for simple monosulfonated azo dyes.
      All of the structures feature alternate organic/inorganic layering, but whereas
      the Mg, Ca, and Li complexes are solvent-separated ion-pair species, the Sr and
      Ba complexes form simple discrete molecules based on metal-sulfonate bonding, and
      the heavy alkali metal complexes utilize a variety of M-O interactions to form 2-
      and 3-dimensional coordination networks. These structural differences are
      rationalized in terms of simple properties of the metals (charge, size, and
      electronegativity) and the steric demands of the arylsulfonate groups. The Ag2
      complex of Orange G is also structurally characterized, and in contrast to the s
      block salts, it is found to exhibit strong Ag pi bonds. In confirmation of the
      above, the crystal structures of [Mg(H2O)6][Og] . 3.33H2O, [Sr(Og)(H2O)7].H2O,
      [Ba(Og)(H2O)7]2 . 2H2O, [Na2(Og)(H2O)6.67], [Na2(Og)(H2O)2(HOEt)],
      [Na0.8K1.2(Og)(H2O)6] . 1.75H2O, [NaRb(Og)(H2O)6.5] . 2.375H2O,
      [Na1.5Cs0.5(Og)(H2O)6] . 0.5H2O, and [Ag2(Og)(H2O)4].H2O are presented.

PMID- 16562953
TI  - One dense and two open chiral metal-organic frameworks: crystal structures and
      physical properties.
AB  - Three 3D robust homochiral helical coordination polymers, [Cu(2,2',3,3'
      H2odpa)(bpy)] (1), {[Ni4(2,2',3,3'-odpa)2(bpy)4(H2O)4].(H2O)16} (2), and
      {[Co4(2,2',3,3'-odpa)2(bpy)4(H2O)4].(H2O)14} (3), have been hydrothermally
      synthesized from a flexible ligand of 2,2',3,3'-odpda (2,2',3,3'-oxydiphthalic
      dianhydride). Compound 1 crystallized in space group P3(1)21 and has a rare
      chiral dense qzd 7.(5)9 topology that incorporates single helical substructures
      with the same accessibility, whereas compounds 2 and 3 crystallized in the space
      group C2 and possessed isostructural 3D chiral open frameworks based on the
      homochiral 2D sheets and 4,4'-bpy pillars. TGA and PXRD analyses show that the
      porous framework of 2 is stable after the removal of solvent water molecules. In
      contrast, 3 changed its structure to an amorphous one because of the simultaneous
      loss of solvent and coordination water molecules. 1 is nearly paramagnetic,
      whereas weak ferromagnetic interactions between M(II) (M = Ni, Co) ions have been
      found in 2 and 3.

PMID- 16562954
TI  - Analogue reaction systems of selenate reductase.
AB  - Analogue reaction systems of selenate reductase, which reduces substrate in the
      overall enzymatic reaction SeO4(2-) + 2H+ + 2e- --> SeO3(2-) + H2O, have been
      developed using bis(dithiolene) complexes of Mo(IV) and W(IV). On the basis of
      the results of EXAFS analysis of the oxidized and reduced enzyme, the minimal
      reaction Mo(IV)OH + SeO4(2-) --> Mo(VI)O(OH) + SeO3(2-) is probable. The square
      pyramidal complexes [M(OMe)(S2C2Me2)2](1-) (M = Mo, W) were prepared as
      structural analogues of the reduced enzyme site. The systems, [ML(S2C2Me2)2](1
      )/SeO4(2-) (L = OMe, OPh, SC6H2-2,4,6-Pr(i)3) in acetonitrile, cleanly reduce
      selenate to selenite in second-order reactions whose negative entropies of
      activation implicate associative transition states. Rate constants at 298 K are
      in the 10(-2)-10(-4) M(-1) s(-1) range with DeltaS++ = -12 to -34 eu. When rate
      constants are compared with previous data for the reduction of (CH2)4SO, Ph3AsO,
      and nitrate by oxygen atom transfer, reactivity trends dependent on the metal,
      axial ligand L, and substrate are identified. As in all other cases of substrate
      reduction by oxo transfer, the kinetic metal effect k(2)W > k(2)Mo holds. A
      proposal from primary sequence alignments suggesting that a conserved Asp residue
      is a likely ligand in the type II enzymes in the DMSO reductase family has been
      pursued by synthesis of the [Mo(IV)(O2CR)(S2C2Me2)2](1-) (R = Ph, Bu(t))
      complexes. The species display symmetrical eta2-carboxylate binding and distorted
      trigonal prismatic stereochemistry. They serve as possible structural analogues
      of the reduced sites of nitrate, selenate, and perchlorate reductases under the
      proposed aspartate coordination. Carboxylate binding has been
      crystallographically demonstrated for one nitrate reductase, but not for the
      other two enzymes.

PMID- 16562955
TI  - Structural, thermodynamic, and mesomorphic consequences of replacing nitrates
      with trifluoroacetate counteranions in ternary lanthanide complexes with
      hexacatenar tridentate ligands.
AB  - The promesogenic hexacatenar tridentate ligands L3(Cn) (I shape) and L4(Cn) (V
      shape) react with trivalent lanthanide trifluoroacetates, Ln((CF3CO2)3, to give
      either monometallic [Ln(Li(Cn))(CF3CO2)3] or trifluoroacetato-bridged bimetallic
      [Ln(Li(Cn))(CF3CO2)3]2 complexes in the solid state, as exemplified by the
      crystal structures of [Lu(L4(CO))(CF3CO2)3(H2O)], [Lu(L4(CO))(CF3CO2)3]2, and
      [La(L3(C4))(CF3CO2)3]2. Although the dimerization process is influenced by the
      competiting complexation of anions or solvent molecules, the coordination of
      CF3CO2- instead of NO3- to Ln(III) produces a significant lengthening of the Ln
      N(ligand) bond distances. This translates into a considerable decrease of the
      affinity of the Li(C12) (i = 3, 4) ligands for Ln(CF3CO2)3 in solution, thus
      leading to significant dissociation of the [Ln(Li(C12))(CF3CO2)3] complexes at
      millimolar concentrations. The thermal properties of these complexes also suffer
      from their limited thermodynamic stability, and the thermotropic liquid
      crystalline phases produced at high temperatures reflect mixtures of different
      species. However, a hexagonal columnar organization characterizes the main
      component in the mesophases obtained with [Ln(L3(C12))(CF3CO2)3] at high
      temperature. A tentative interpretation of the small-angle X-ray scattering
      (SAXS) profiles suggests that disklike dimers of [Ln(L3(C12))(CF3CO2)3]2 are
      packed along the columnar axes. For [Ln(L4(C12))(CF3CO2)3], SAXS profiles are
      compatible with a lamellar organization in the mesophases originating from the
      existence of rodlike dimers of [Ln(L4(C12))(CF3CO2)3]2 as the major component in
      the liquid-crystal state.

PMID- 16562957
TI  - Linear polypseudorotaxanes possessing many metal centers constructed from
      inclusion complexes of alpha-, beta-, and gamma-cyclodextrins with 4,4'
      dipyridine.
AB  - Three cyclodextrin-based complexes, 1-3, bearing external coordination sites for
      metal cations were prepared in satisfactory yields (over 50%) by reactions of
      alpha-, beta-, and gamma-cyclodextrins with 4,4'-dipyridine in aqueous solutions.
      Subsequently, these inclusion complexes were further assembled to form linear
      polypseudorotaxanes 4-6 through the coordination linkage of Ni(II) or Cu(II)
      ions, and their assembly behaviors were comprehensively investigated in both
      solutions and the solid state by means of 1H NMR, FT-IR, UV-vis spectroscopy,
      conductivity titration, powder X-ray diffraction patterning, thermogravimetric
      and differential thermal analysis, scanning electron microscopy, scanning
      tunneling microscopy, and transmission electron microscopy. The results showed
      that these polypseudorotaxanes existed as individual linear arrays at a low
      concentration but tended to form polymeric rodlike fibers at a relatively high
      concentration. Significantly, the volume of the cyclodextrin cavity used not only
      determined the inclusion complexation stoichiometry between cyclodextrin and 4,4'
      dipyridine but also predominated the morphology of resulting polypseudorotaxanes.

PMID- 16562956
TI  - Copper-dioxygen adducts and the side-on peroxo dicopper(II)/bis(mu-oxo)
      dicopper(III) equilibrium: Significant ligand electronic effects.
AB  - The variation of ligand para substituents on pyridyl donor groups of tridentate
      amine copper(I) complexes was carried out in order to probe electronic effects on
      the equilibrium between mu-eta2:eta2-(side-on)-peroxo [Cu(II)2(O2(2-))]2+ and
      bis(mu-oxo) [Cu(III)2(O(2-))2] species formed upon reaction with O2. [Cu(I)(R
      PYAN)(MeCN)n]B(C6F5)4 (R-PYAN = N-[2-(4-R-pyridin-2-yl)-ethyl]-N,N',N'-trimethyl
      propane-1,3-diamine, R = NMe2, OMe, H, and Cl) (1R) vary over a narrow range in
      their Cu(II)/Cu(I) redox potentials (E(1/2) vs Fe(cp)2(+/0) = -0.40 V for
      1(NMe2), -0.38 V for 1(OMe), -0.33 V for 1H, and -0.32 V for 1Cl) and in C-O
      stretching frequencies of their carbonyl adducts, 1R-CO: nu(C-O) = 2080, 2086,
      2088, and 2090 cm(-1) for R = NMe2, OMe, H, and Cl, respectively. However, within
      this range of electronic properties for 1R, dioxygen reactivity is significantly
      affected. The reaction of 1Cl or 1H with O2 at -78 degrees C in CH2Cl2 gives UV
      vis and resonance Raman spectra indicative of a mu-eta2:eta2-(side-on)-peroxo
      dicopper(II) adduct (2R). Compound 1(OMe) reacts with O2, yielding equilibrium
      mixtures of side-on peroxo (2(OMe)) and bis(mu-oxo) (3(OMe)) species. Oxygenation
      of 1(NMe2) leads to the sole generation of the bis(mu-oxo) dicopper(III) complex
      (3(NMe2)). A solvent effect was also observed; in acetone or THF, increased
      ratios of bis(mu-oxo) relative to side-on peroxo complex are observed. Thus, the
      equilibrium between a dicopper side-on peroxo and bis(mu-oxo) species can be
      tuned by ligand design-specifically, more electron donating ligands favor the
      formation of the latter isomer, and the peroxo/bis(mu-oxo) equilibrium can be
      shifted from one extreme to the other within the same ligand system. Observations
      concerning the reactivity of the dioxygen adducts 2H and 3(NMe2) toward external
      substrates are also presented.

PMID- 16562958
TI  - Studies of a dinuclear manganese complex with phenoxo and bis-acetato bridging in
      the Mn2(II,II) and Mn2(II,III) states: Coordination structural shifts and
      oxidation state control in bridged dinuclear complexes.
AB  - The dinucleating ligand, 2,6-bis{[(2-(2-pyridyl)ethyl)(2-pyridylmethyl)-amino]
      methyl}-4-methylphenol) (L1OH) reacts with Mn(ClO4)2.6H2O to form the dinuclear
      complex [Mn2(II,II)(L1O)(mu-OOCCH3)2]ClO4 (1). The electrolytic oxidation of 1 at
      0.7 V (vs Ag/AgCl) produces the mixed valent complex [Mn2(II,III)(L1O)(mu
      OOCCH3)2](ClO4)2 (1ox) quantitatively, while electrolysis at 0.20 V converts 1ox
      back to 1. X-ray crystallographic structures show that both 1 and 1ox are
      dinuclear complexes in which the two manganese ions are each in distorted
      octahedral coordination environments bridged by the phenoxo oxygen and two
      acetate ions. The structural changes that occur upon the oxidation 1 to 1ox
      suggest an extended pi-bonding system involving the phenoxo ring C-O(phenoxo)
      Mn(II)-N(pyridyl) chain. In addition, as 1 is oxidized to 1ox, the rearrangements
      in the coordination sphere resulting from the oxidation of one Mn(II) ion to
      Mn(III) are transmitted via the bridging Mn-O(phenoxo) bonds and cause structural
      changes that render the site of the second manganese ion unfit for the +3 state
      and hence unstable to reduction. Thus the electrolytic oxidation of 1ox in
      acetonitrile at 1.20 V takes up slightly greater than 1 F of charge/mol of 1ox,
      but the starting complex, 1ox, is recovered, showing the instability of the
      Mn2(III,III) state that is formed with respect to reduction to 1ox. Variable
      temperature magnetic susceptibility measurements of 1 and 1ox over the
      temperature range from 1.8 to 300 K can be modeled with magnetic coupling
      constants J = -4.3 and -4.1 cm(-1), respectively showing the weak
      antiferromagnetic coupling between the two manganese ions in each dinuclear
      complex, which is commonly observed among similar phenoxo- and bis-1,3
      carboxylato-bridged dinuclear Mn2(II,II) and Mn2(II,III) complexes.

PMID- 16562959
TI  - Catalytic mechanism of dopamine beta-monooxygenase mediated by Cu(III)-oxo.
AB  - Mechanisms of dopamine hydroxylation by the Cu(II)-superoxo species and the
      Cu(III)-oxo species of dopamine beta-monooxygenase (DBM) are discussed using
      QM/MM calculations for a whole-enzyme model of 4700 atoms. A calculated
      activation barrier for the hydrogen-atom abstraction by the Cu(II)-superoxo
      species is 23.1 kcal/mol, while that of the Cu(III)-oxo, which can be viewed as
      Cu(II)-O*, is 5.4 kcal/mol. Energies of the optimized radical intermediate in the
      superoxo- and oxo-mediated pathways are 18.4 and -14.2 kcal/mol, relative to the
      corresponding reactant complexes, respectively. These results demonstrate that
      the Cu(III)-oxo species can better mediate dopamine hydroxylation in the protein
      environment of DBM. The side chains of three amino acid residues (His415, His417,
      and Met490) coordinate to the Cu(B) atom, one of the copper sites in the
      catalytic core that plays a role for the catalytic function. The hydrogen-bonding
      network between dopamine and the three amino acid residues (Glu268, Glu369, and
      Tyr494) plays an essential role in substrate binding and the stereospecific
      hydroxylation of dopamine to norepinephrine. The dopamine hydroxylation by the
      Cu(III)-oxo species is a downhill and lower-barrier process toward the product
      direction with the aid of the protein environment of DBM. This enzyme is likely
      to use the high reactivity of the Cu(III)-oxo species to activate the benzylic C
      H bond of dopamine; the enzymatic reaction can be explained by the so-called
      oxygen rebound mechanism.

PMID- 16562960
TI  - Structure determination and relative properties of novel noncentrosymmetric
      borates MM'4(BO3)3 (M = Na, M' = Ca and M = K, M' = Ca, Sr).
AB  - A series of novel noncentrosymmetric borates, MM'4(BO3)3 (M = Na, M' = Ca; M = K,
      M' = Ca, Sr), have been successfully synthesized via a standard solid-state
      reaction. The crystal structures have been determined by the SDPD (structure
      determination from powder diffraction) method. They crystallize in the
      noncentrosymmetric space group Ama2 with the following lattice parameters: a =
      10.68004(11) A, b = 11.28574(11) A, c = 6.48521(6) A for NaCa4(BO3)3; a =
      10.63455(10) A, b = 11.51705(11) A, c = 6.51942(6) A for KCa4(BO3)3; and a =
      11.03843(8) A, b = 11.98974(9) A, c = 6.88446(5) A for KSr4(BO3)3. The
      fundamental building units are isolated BO3 anionic groups. Their second harmonic
      generation (SHG) coefficients were one-half (NaCa4(BO3)3), one-third
      (KCa4(BO3)3), and two-thirds (KSr4(BO3)3) as large as that of KH2PO4 (KDP). The
      infrared and UV-vis spectra of the three compounds are discussed. Moreover, a
      comparison of the structures of these novel compounds and three other novel cubic
      compounds with the same formula, MM'4(BO3)3 (M = Li, M' = Sr; M = Na, M' = Sr,
      Ba), is presented here.

PMID- 16562961
TI  - Structure and photochemical properties of (mu-alkoxo)bis(mu
      carboxylato)diruthenium complexes with naphthylacetate ligands.
AB  - Two new dinuclear Ru(III) complexes containing naphthalene moieties,
      K[Ru2(dhpta)(mu-O2CCH2-1-naph)2] (1) and K[Ru2(dhpta)(mu-O2CCH2-2-naph)2] (2)
      (H5dhpta = 1,3-diamino-2-hydroxypropane-N,N,N',N'-tetraacetic acid, naph-1
      CH2CO2H = 1-naphthylacetic acid, naph-2-CH2CO2H = 2-naphthylacetic acid), were
      synthesized. Complex 2 crystallized as an orthorhombic system having a space
      group of Pbca with unit cell parameters a = 10.6200(5) A, b = 20.270(1) A, c =
      35.530(2) A, and Z = 8. EXAFS analysis of 1 and 2 in the solid states and in
      solution clarified that the dinuclear structures of 1 and 2 were kept in DMSO
      solutions. Variable-temperature magnetic susceptibility data indicated that the
      two Ru(III) centers are strongly antiferromagnetically coupled as shown by the
      large coupling constants, J = -581 cm(-1) (1) and -378 cm(-1) (2). In the cyclic
      voltammograms of 1 and 2, one oxidation peak and two reduction peaks which were
      assigned to the redox reaction of the ruthenium moieties were observed in DMF.
      The large conproportionation constants estimated from the reduction potentials of
      Ru(III)Ru(III) and Ru(III)Ru(II) indicated the great stability of the mixed
      valent state. The mixed-valent species [Ru(III)Ru(II)(dhpta)(mu-O2CCH2-R)2](2-)
      (R = 1-naph (6) and R = 2-naph (7)) were prepared by controlled potential
      electrolysis of 1 and 2 in DMF. The electronic absorption spectra of 6 and 7 were
      similar to that of [Ru(III)Ru(II) (dhpta)(mu-O2CCH3)2](2-) which is a typical
      Class II type mixed-valent complex. The fluorescence decay of 1 and 2 indicated
      that there are two quenching processes which come from the excimer and monomer
      states. The short excimer lifetimes of 1 and 2 were ascribed to the energy
      transfer from the naphthyl moieties to the Ru centers. The different excimer
      ratio between 1 and 2 suggested that the excimer formation is affected by the
      conformation of the naphthyl moieties in the diruthenium(III) complexes.

PMID- 16562962
TI  - Developing the {M(CO)3}+ core for fluorescence applications: Rhenium tricarbonyl
      core complexes with benzimidazole, quinoline, and tryptophan derivatives.
AB  - Tridentate ligands derived from benzimidazole, quinoline, and tryptophan have
      been synthesized, and their reactions with [NEt4]2[Re(CO)3Br3] have been
      investigated. The complexes 1-4 and 6 and 7 exhibit fac-{Re(CO)3N3} coordination
      geometry in the cationic molecular units, while 5 exhibits fac-{Re(CO)3N2O}
      coordination for the neutral molecular unit, where N3 and N2O refer to the ligand
      donor groups. The ligands bis(1-methyl-1H-benzoimidazol-2-ylmethyl)amine (L1),
      [bis(1-methyl-1H-benzoimidazol-2-ylmethyl)amino]acetic acid ethyl ester (L2),
      [bis(1-methyl-1H-benzoimidazol-2-ylmethy)amino]acetic acid methyl ester (L3),
      [bis(quinolin-2-ylmethyl)amino]acetic acid methyl ester (L4), 3-(1-methyl-1H
      indol-3-yl)-2-[(pyridin-2-ylmethyl)amino]propionic acid (L5), 2-[bis(pyridin-2
      ylmethyl)amino]-3-(1-methyl-1H-indol-3-yl)propionic acid (L6), and 2
      [bis(quinolin-2-ylmethyl)amino]-3-(1-methyl-1H-indol-3-yl)propionic acid (L7)
      were obtained in good yields and characterized by elemental analysis, 1D and 2D
      NMR, and high-resolution mass spectrometry (HRMS). The rhenium complexes were
      obtained in 70-85% yields and characterized by elemental analysis, 1D and 2D NMR,
      HRMS, IR, UV, and luminescence spectroscopy, as well as X-ray crystallography for
      [Re(CO)3(L1)]Br (1), {[Re(CO)3(L2)]Br}2.NEt4Br . 8.5H2O (3(2).NEt4Br . 8.5H2O),
      [Re(CO)3(L4)]Br (4), and [Re(CO)3(L6)]Br (6). Crystal data for C21H19BrN5O3Re
      (1): monoclinic, P2(1)/c, a = 13.1851(5) A, b = 16.1292(7) A, c = 10.2689(4) A,
      beta = 99.353(1) degrees , V = 2154.8(2) A3, Z = 4. Crystal data for
      C56H73Br3N11O18.50 Re2 (3(2).NEt4Br . 8.5H2O): monoclinic, C2/c, a = 34.7760(19)
      A, b = 21.1711(12) A, c = 20.3376(11) A, beta = 115.944(1) degrees , V =
      13464.5(1) A3, Z = 8. Crystal data for C26H21BrN3O5Re (4): monoclinic, P2(1)/c, a
      = 16.6504(6) A, b = 10.1564(4) A, c = 14.6954(5) A, beta = 96.739(1) degrees , V
      = 2467.9(2) A3, Z = 4. Crystal data for C27H24BrN4O5Re (6): monoclinic, P2(1), a
      = 8.7791(9) A, b = 16.312(2) A, c = 8.9231(9) A, beta = 90.030(1) degrees , V =
      1277.8(2) A3, Z = 2.

PMID- 16562963
TI  - Calcium tetraboride-does it exist? Synthesis and properties of a carbon-doped
      calcium tetraboride that is isotypic with the known rare earth tetraborides.
AB  - Crystalline samples of carbon-doped CaB4 were synthesized by solid-state
      reactions in sealed niobium ampules from the elements Ca, B, and C. The structure
      was determined by single-crystal X-ray diffraction (P4/mbm, Z = 4, a = 7.0989(7)
      A, c = 4.1353(5) A, R1 = 0.026, and wR2 = 0.058) revealing an atom arrangement
      containing a three-dimensional boron network built up from B6 octahedra and B2
      dumbbells which is well-known from the structures of rare earth tetraborides.
      Crystals of CaB(4-x)Cx are black with a metallic luster and behave stable against
      mineral acids. Band structure calculations indicate that CaB4 is a stable
      semiconducting compound with a narrow band gap and that carbon should not
      necessarily be required for the stability of this compound. The presence of
      carbon in the crystalline samples of CaB(4-x)Cx was indicated by electron energy
      loss spectroscopy, but the carbon content in the samples was estimated to be less
      than 5% according to inductively coupled plasma-atomic emission spectrometry
      measurements. The distribution of boron and carbon atoms in the structure was
      investigated by means of 11B and 13C solid-state magic angle spinning NMR.
      Measurements of the magnetic susceptibility indicate a temperature-independent
      paramagnetism down to 20 K.

PMID- 16562964
TI  - The imidazole role in strontium beta-diketonate complexes formation.
AB  - A selection of new strontium beta-diketonate derivatives (imH2)2[Sr2(beta-dike)6]
      [where imH = imidazole and beta-dike = tfac (tfacH = 1,1,1-trifluoro-2,4
      pentanedione), tfbz (tfbzH = 1,1,1-trifluoro-4-phenyl-2,4-butanedione), or hfac
      (hfacH = 1,1,1,5,5,5-hexafluoro-2,4-pentanedione)], [Sr2(tfac)4(Meim)2(H2O)2],
      (MeimH)2[Sr(beta-dike)4] (where Meim = 1-methylimidazole and beta-dike = tfbz or
      hfac), [Sr2(thd)4(imH)2(EtOH)], and [Sr2(thd)4(Meim)2(EtOH)] (where thdH =
      2,2,6,6-tetramethyl-3,5-heptanedione) have been synthesized and fully
      characterized. (imH2)2[Sr2(beta-dike)6] and (MeimH)2[Sr(beta-dike)4] are di- and
      mononuclear Sr anionic complexes, respectively, while [Sr2(tfac)4(Meim)2(H2O)2],
      [Sr2(thd)4(imH)2(EtOH)], and [Sr2(thd)4(Meim)2(EtOH)] are neutral dinuclear
      molecular derivatives. The derivative (imH2)2[Sr2(hfac)6] slowly decomposes in
      solution under aerobic conditions, giving (imH2)2[Sr(H2O)2(tfa)3](tfa) (tfaH =
      trifluoroacetic acid), which is an ionic compound containing polynuclear anionic
      chains composed of Sr(H2O)2(tfa)3 units. When a deficiency of imH is employed,
      the thdH proligand forms not only the dinuclear derivative
      [Sr2(thd)4(imH)2(EtOH)] but also an additional product with the formula
      [Sr(thd)2(H2O)2(EtOH)], in which the Sr atom is seven-coordinated. A complete
      solid-state characterization has been accomplished by comparing X-ray and solid
      state 13C NMR data. Elucidation of the H-bond interaction between the
      heterocyclic rings and metal complexes by cross-polarization magic-angle-spinning
      15N NMR is also reported.

PMID- 16562965
TI  - Proton-transfer and H2-elimination reactions of main-group hydrides EH4- (E = B,
      Al, Ga) with alcohols.
AB  - The reaction of the isostructural anions of group 13 hydrides EH4- (E = B, Al,
      Ga) with proton donors of different strength (CH3OH, CF3CH2OH, and CF3OH) was
      studied with different theoretical methods [DFT/B3LYP and second-order Moller
      Plesset (MP2) using the 6-311++G(d,p) basis set]. The results show the general
      mechanism of the reaction: the dihydrogen-bonded (DHB) adduct (EH...HO) formation
      leads through the activation barrier to the next concerted step of H2 elimination
      and alkoxo product formation. The structures, interaction energies (calculated by
      different approaches including the energy decomposition analysis), vibrational E
      H modes, and electron-density distributions were analyzed for all of the DHB
      adducts. The transition state (TS) is the dihydrogen complex stabilized by a
      hydrogen bond with the anion [EH3(eta2-H2)...OR-]. The single exception is the
      reaction of BH4- with CF3OH exhibiting two TSs separated by a shallow minimum of
      the BH3(eta2-H2)...OR- intermediate. The structures and energies of all of the
      species were calculated, leading to the establishment of the potential energy
      profiles for the reaction. A comparison is made with the mechanism of the proton
      transfer reaction to transition-metal hydrides. The solvent influence on the
      stability of all of the species along the reaction pathway was accounted for by
      means of polarizable conductor calculation model calculations in tetrahydrofuran
      (THF). Although in THF the DHB intermediates, the TSs, and the products are
      destabilized with respect to the separated reactants, the energy barriers for the
      proton transfer are only slightly affected by the solvent. The dependence of the
      energies of the DHB complexes, TSs, and products as well as the energy barriers
      for the H2 release on the central atom and the proton donor strength is also
      discussed.

PMID- 16562966
TI  - Three in one: TSA, TSA', and SA units in one crystal structure of a yttrium(III)
      complex with a monophosphinated H4dota analogue.
AB  - Compound [Y(Hdo3aP(ABn))(H2O)][Y(Hdo3aP(ABn))].6H2O.iPrOH, where H4do3aP(ABn) is
      1,4,7,10-tetraazacyclododecane-1,4,7-triacetic-10-methyl(4-aminobenzylphosphinic)
      acid, a monophosphinate analogue of H4dota, was prepared in the solid state and
      studied using X-ray crystallography. In contrast to all single-crystal structures
      of complexes of H4dota-like ligands published before, three distinct units were
      found in one cell: two species adopting a twisted-square-antiprismatic
      configuration with (TSA) and without (TSA') a coordinated water molecule and one
      isomer with a square-antiprismatic configuration (SA). In addition, this is the
      first complex with the H4dota-like ligand for which the structures of three
      possible species were determined in the solid state.

PMID- 16562967
TI  - Crystal structures of triazine-3-thione derivatives by reaction with copper and
      cobalt salts.
AB  - The reaction of 5-methoxy-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione
      L1H2OCH3 with copper(II) chloride leads to the formation of an organic molecule
      L2 containing two triazine rings linked by a new S-S bond. A binuclear copper(II)
      complex, 1, containing L1 is also isolated. The reaction of L1H2OCH3 with
      copper(I) chloride yields a hexanuclear cluster of copper(I), 2, in which the
      copper atoms form a distorted octahedron with the ligand L1 acting as an NS
      chelate and sulfur bridge, giving to the copper ion a trigonal geometry by one N
      and two S atoms. In any reaction of the disulfide L2 with metal salts, complexes
      containing this molecule are isolated. Reactions with copper(I) and copper(II)
      chloride and nickel(II) and cadmium(II) nitrate produce the S-S bond cleavage,
      giving complexes containing the triazine L1 behaving as the NS anion, which show
      spectroscopic characteristics identical with those formed by reaction with
      L1H2OCH3. However, the reaction with cobalt(II) nitrate gives a low-spin
      octahedral cobalt(III) complex, in which an asymmetric rupture of the disulfide
      L2 has been produced, giving an unexpected complex with a new ligand and keeping
      the S-S bond.

PMID- 16562968
TI  - Biologically relevant phosphoranes: structural characterization of glucofuranose-
      and xylofuranose-based phosphoranes.
AB  - Carbohydrate-based phosphoranes were synthesized by reacting 2,2'
      ethylidenebis(4,6-di-tert-butylphenyl)fluorophosphite with 1,2-O-isopropylidene
      alpha-D-glucofuranose, beta-chloralose, and 1,2-isopropylidene-alpha-D
      xylofuranose to form the monocyclic biophosphoranes 1-3, respectively, in the
      presence of N-chlorodiisopropylamine. Synthesis of the monocyclic biophosphorane
      4 was achieved by reacting tris(2,6-di-isopropylphenyl)phosphite with 1,2-O
      isopropylidene-alpha-D-glucofuranose in the presence of N-chlorodiisopropylamine.
      X-ray analysis of 1-4 revealed trigonal bipyramidal structures with the
      carbohydrate components occupying axial-equatorial sites. An eight-membered ring
      in 1-3 occupied diequatorial sites of the trigonal bipyramid. Solution and solid
      state 31P and solution 19F, 1H, and 13C NMR measurements including variable
      temperature and correlation spectroscopy studies established retention of the
      solid state structure in solution. A dynamic equilibrium exists among two
      isomeric forms. These biophosphoranes serve as models for active sites of
      phosphoryl transfer enzymes. The rapid exchange process reorients the
      carbohydrate component of the trigonal bipyramidal phosphorane. At an active
      site, this type of pseudorotational behavior provides a mechanism that could
      bring another active site residue into play and account for a means by which some
      phosphoryl transfer enzymes express promiscuous behavior.

PMID- 16562969
TI  - DNA oxidation in anionic reverse micelles: ruthenium-mediated damage at Guanine
      in single- and double-stranded DNA.
AB  - One-electron guanine oxidation in DNA has been investigated in anionic reverse
      micelles (RMs). A photochemical method for generating Ru3+ from the ruthenium
      polypyridyl complex tris(2-2'-bipyridine)ruthenium(II) chloride ([Ru(bpy)3]Cl2)
      is combined with high-resolution polyacrylamide gel electrophoresis (PAGE) to
      quantify piperidine-labile guanine oxidation products. As characterized by
      emission spectroscopy of Ru(bpy)3(2+), the addition of DNA to RMs containing
      Ru(bpy)3(2+) does not perturb the environment of Ru(bpy)3(2+). The steady-state
      quenching efficiency of Ru(bpy)3(2+) with K3[Fe(CN)6] in buffer solution is
      approximately 2-fold higher than that observed in RMs. Consistent with the
      difference in quenching efficiency in the two media, a 1.5-fold higher yield of
      piperidine-labile damage products as monitored by PAGE is observed for duplex
      oligonucleotide in buffer vs RMs. In contrast, a 13-fold difference in the yield
      of PAGE-detected G oxidation products is observed when single-stranded DNA is the
      substrate. Circular dichroism spectra showed that single-stranded DNA undergoes a
      structural change in anionic RMs. This structural change is potentially due to
      cation-mediated adsorption of the DNA phosphates on the anionic headgroups of the
      RMs, leading to protection of the guanine from oxidatively generated damage.

PMID- 16562970
TI  - Insertion of the Ga(I) bis-imidinate Ga(DDP) into the metal halogen bonds of
      Rh(I) complexes. How electrophilic are coordinated Ga(DDP) fragments?
AB  - The reactivity of Ga(DDP) (DDP = 2-((2,6-diisopropylphenyl)amino-4-((2,6
      diisopropylphenyl)imino)-2-pentene) towards the rhodium-chloride bonds of
      [RhCl(PPh3)3] and [RhCl(COE)2]2 (COE = cyclooctene) is investigated. Reaction of
      the first complex leads to [(Ph3P)2Rh{Ga(DDP)}(mu-Cl)] (1), exhibiting a chloride
      bridging the gallium and the rhodium atoms, whereas the second complex leads to a
      full insertion of the Ga(DDP) ligand into the Rh-Cl bond giving
      [(COE)(benzene)Rh{(DDP)GaCl}] (2) on coordination of the solvent C6H6. Compounds
      1 und 2 readily react with the halide abstracting reagent Tl[BArF] (BArF = B[3,5
      (CF3)2C6H3]4), yet the products could not be isolated and characterized because
      of their lability. The Au(I) complex [{(DDP)Ga}Au{Ga(DDP)}Cl] reacts with
      Na[BArF] giving the linear, symmetric cationic complex [{(DDP)Ga.THF}2Au][BArF]
      (3.2THF), exhibiting two THF molecules coordinated to the Ga(DDP) moieties.

PMID- 16562972
TI  - Harvesting chemical information from the Internet using a distributed approach:
      ChemXtreme.
AB  - The Internet is a comprehensive resource of chemical information which is at the
      same time largely unstructured. It provides a wealth of scientific information
      such as experimental data and requires a suitable automated data mining and
      analysis tool for its meaningful exploration. The Java based software presented
      here, ChemXtreme, is developed for harvesting chemical information from the
      Internet employing the Google API in combination with a distributed client/server
      text analysis architecture based on JavaRMI. It represents the first and until
      now the only toolkit for automated structured data retrieval from the Internet
      which is itself open source. ChemXtreme employs the "search the search engine"
      strategy, where the URLs returned from the search engine are analyzed further via
      textual pattern analysis. This process resembles the manual analysis of the hit
      list, where relevant data are captured and, by means of human intervention, are
      mined into a format suitable for further analysis. ChemXtreme on the other hand
      transforms chemical information automatically into a structured format suitable
      for storage in databases and further analysis and also provides links to the
      original information source. The query data retrieved from the search engine by
      the server is encoded, encrypted, and compressed and then sent to all the
      participating active clients in the network for parsing. Relevant information
      identified by the clients on the retrieved Web sites is sent back to the server,
      verified, and added to the database for data mining and further analysis. The
      distributed further analysis of URLs in a client/server architecture scales very
      favorably, thus producing only minimal overhead.

PMID- 16562973
TI  - New methods for ligand-based virtual screening: use of data fusion and machine
      learning to enhance the effectiveness of similarity searching.
AB  - Similarity searching using a single bioactive reference structure is a well
      established technique for accessing chemical structure databases. This paper
      describes two extensions of the basic approach. First, we discuss the use of
      group fusion to combine the results of similarity searches when multiple
      reference structures are available. We demonstrate that this technique is notably
      more effective than conventional similarity searching in scaffold-hopping
      searches for structurally diverse sets of active molecules; conversely, the
      technique will do little to improve the search performance if the actives are
      structurally homogeneous. Second, we make the assumption that the nearest
      neighbors resulting from a similarity search, using a single bioactive reference
      structure, are also active and use this assumption to implement approximate forms
      of group fusion, substructural analysis, and binary kernel discrimination. This
      approach, called turbo similarity searching, is notably more effective than
      conventional similarity searching.

PMID- 16562974
TI  - Virtual screening using binary kernel discrimination: analysis of pesticide data.
AB  - This paper discusses the use of binary kernel discrimination (BKD) for
      identifying potential active compounds in lead-discovery programs. BKD was
      compared with established virtual screening methods in a series of experiments
      using pesticide data from the Syngenta corporate database. It was found to be
      superior to methods based on similarity searching and substructural analysis but
      inferior to a support vector machine. Similar conclusions resulted from
      application of the methods to a pesticide data set for which categorical activity
      data were available.

PMID- 16562976
TI  - On the use of 1H and 13C 1D NMR spectra as QSPR descriptors.
AB  - Recently, 1D NMR and IR spectra have been proposed as descriptors containing 3D
      information. And, as such, said to be suitable for making QSAR and QSPR models
      where 3D molecular geometries matter, for example, in binding affinities. This
      paper presents a study on the predictive power of 1D NMR spectra-based QSPR
      models using simulated proton and carbon 1D NMR spectra. It shows that the
      spectra-based models are outperformed by models based on theoretical molecular
      descriptors and that spectra-based models are not easy to interpret. We therefore
      conclude that the use of such NMR spectra offers no added value.

PMID- 16562975
TI  - Virtual screening using binary kernel discrimination: effect of noisy training
      data and the optimization of performance.
AB  - Binary kernel discrimination (BKD) uses a training set of compounds, for which
      structural and qualitative activity data are available, to produce a model that
      can then be applied to the structures of other compounds in order to predict
      their likely activity. Experiments with the MDL Drug Data Report database show
      that the optimal value of the smoothing parameter, and hence the predictive power
      of BKD, is crucially dependent on the number of false positives in the training
      set. It is also shown that the best results for BKD are achieved using one
      particular optimization method for the determination of the smoothing parameter
      that lies at the heart of the method and using the Jaccard/Tanimoto coefficient
      in the kernel function that is used to compute the similarity between a test set
      molecule and the members of the training set.

PMID- 16562977
TI  - Videoconferencing and other distance education techniques in chemoinformatics
      teaching and research at Indiana University.
AB  - At a time when the demand for people with expertise in chemoinformatics is
      increasing, there is still only a very small number of academic institutions that
      offer chemoinformatics-related classes and degrees. The distance education (DE)
      approach allows both learning and research to be carried out at multiple
      geographic locations and institutions, thus leveraging the few educational
      offerings that are available. In this paper, distance education techniques and
      technologies (with emphasis on videoconferencing) are reviewed, and examples of
      how they are used to increase the accessibility of chemoinformatics education and
      research at the Indiana University School of Informatics are presented.

PMID- 16562978
TI  - Scaffold hopping using clique detection applied to reduced graphs.
AB  - Similarity-based methods for virtual screening are widely used. However,
      conventional searching using 2D chemical fingerprints or 2D graphs may retrieve
      only compounds which are structurally very similar to the original target
      molecule. Of particular current interest then is scaffold hopping, that is, the
      ability to identify molecules that belong to different chemical series but which
      could form the same interactions with a receptor. Reduced graphs provide summary
      representations of chemical structures and, therefore, offer the potential to
      retrieve compounds that are similar in terms of their gross features rather than
      at the atom-bond level. Using only a fingerprint representation of such graphs,
      we have previously shown that actives retrieved were more diverse than those
      found using Daylight fingerprints. Maximum common substructures give an
      intuitively reasonable view of the similarity between two molecules. However,
      their calculation using graph-matching techniques is too time-consuming for use
      in practical similarity searching in larger data sets. In this work, we exploit
      the low cardinality of the reduced graph in graph-based similarity searching. We
      reinterpret the reduced graph as a fully connected graph using the bond-distance
      information of the original graph. We describe searches, using both the maximum
      common induced subgraph and maximum common edge subgraph formulations, on the
      fully connected reduced graphs and compare the results with those obtained using
      both conventional chemical and reduced graph fingerprints. We show that graph
      matching using fully connected reduced graphs is an effective retrieval method
      and that the actives retrieved are likely to be topologically different from
      those retrieved using conventional 2D methods.

PMID- 16562979
TI  - Assessing the scaffold diversity of screening libraries.
AB  - Medicinal chemists have traditionally realized assessments of chemical diversity
      and subsequent compound acquisition, although a recent study suggests that
      experts are usually inconsistent in reviewing large data sets. To analyze the
      scaffold diversity of commercially available screening collections, we have
      developed a general workflow aimed at (1) identifying druglike compounds, (2)
      clustering them by maximum common substructures (scaffolds), (3) measuring the
      scaffold diversity encoded by each screening collection independently of its
      size, and finally (4) merging all common substructures in a nonredundant scaffold
      library that can easily be browsed by structural and topological queries.
      Starting from 2.4 million compounds out of 12 commercial sources, four categories
      of libraries could be identified: large- and medium-sized combinatorial libraries
      (low scaffold diversity), diverse libraries (medium diversity, medium size), and
      highly diverse libraries (high diversity, low size). The chemical space covered
      by the scaffold library can be searched to prioritize scaffold-focused libraries.

PMID- 16562980
TI  - Relationships between Molecular Complexity, Biological Activity, and Structural
      Diversity.
AB  - Following the theoretical model by Hann et al. moderately complex structures are
      preferable lead compounds since they lead to specific binding events involving
      the complete ligand molecule. To make this concept usable in practice for library
      design, we studied several complexity measures on the biological activity of
      ligand molecules. We applied the historical IC50/EC50 summary data of 160 assays
      run at Novartis covering a diverse range of targets, among them kinases,
      proteases, GPCRs, and protein-protein interactions, and compared this to the
      background of "inactive" compounds which have been screened for 2 years but have
      never shown any activity in any primary screen. As complexity measures we used
      the number of structural features present in various molecular fingerprints and
      descriptors. We found generally that with increasing activity of the ligands,
      their average complexity also increased, and we could therefore establish a
      minimum number of structural features in each descriptor needed for biological
      activity. Especially well suited in this context were the Similog keys and
      circular substructure fingerprints. These are those descriptors, which also
      perform especially well in the identification of bioactive compounds by
      similarity search, suggesting that structural features encoded in these
      descriptors have a high relevance for bioactivity. Since the number of features
      correlates with the number of atoms present in the molecule, also the number of
      atoms serves as a reasonable complexity measure and larger molecules have, in
      general, higher activities. Due to the relationship between feature counts and
      densities on one hand and biological activity on the other, the size bias present
      in almost all similarity coefficients becomes especially important. Diversity
      selections using these coefficients can influence the overall complexity of the
      resulting set of molecules, which has an impact on the biological activity that
      they exhibit. Using sphere-exclusion based diversity selection methods, such as
      OptiSim together with the Tanimoto dissimilarity, the average feature count
      distribution of the resulting selections is shifted toward lower complexity than
      that of the original set, particularly when applying tight diversity constraints.
      This size bias reduces the fraction of molecules in the subsets having the
      complexity required for a high, submicromolar activity. None of the diversity
      selection methods studied, namely OptiSim, divisive K-means clustering, and self
      organizing maps, yielded subsets covering the activity space of the IC50 summary
      data set better than subsets selected randomly.

PMID- 16562981
TI  - Toxicity-indicating structural patterns.
AB  - We describe a toxicity alerting system for uncharacterized compounds, which is
      based upon comprehensive tables of substructure fragments that are indicative of
      toxicity risk. These tables were derived computationally by analyzing the RTECS
      database and the World Drug Index. We provide, free of charge, a Java applet for
      structure drawing and toxicity risk assessment. In an independent investigation,
      we compared the toxicity classification performance of naive Bayesian clustering,
      k next neighbor classification, and support vector machines. To visualize the
      chemical space of both toxic and druglike molecules, we trained a large self
      organizing map (SOM) with all compounds from the RTECS database and the IDDB. In
      summary, we found that a support vector machine performed best at classifying
      compounds of defined toxicity into appropriate toxicity classes. Also, SOMs
      performed excellently in separating toxic from nontoxic substances. Although
      these two methods are limited to compounds that are structurally similar to known
      toxic substances, our fragment-based approach extends predictions to compounds
      that are structurally dissimilar to compounds used in the training set.

PMID- 16562982
TI  - The molecule evoluator. An interactive evolutionary algorithm for the design of
      drug-like molecules.
AB  - We developed a software tool to design drug-like molecules, the "Molecule
      Evoluator", which we introduce and describe here. An atom-based evolutionary
      approach was used allowing both several types of mutation and crossover to occur.
      The novelty, we claim, is the unprecedented interactive evolution, in which the
      user acts as a fitness function. This brings a human being's creativity, implicit
      knowledge, and imagination into the design process, next to the more standard
      chemical rules. Proof-of-concept was demonstrated in a number of ways, both
      computationally and in the lab. Thus, we synthesized a number of compounds
      designed with the aid of the Molecule Evoluator. One of these is described here,
      a new chemical entity with activity on alpha-adrenergic receptors.

PMID- 16562983
TI  - Mining a chemical database for fragment co-occurrence: discovery of "chemical
      cliches".
AB  - Nowadays millions of different compounds are known, their structures stored in
      electronic databases. Analysis of these data could yield valuable insights into
      the laws of chemistry and the habits of chemists. We have therefore explored the
      public database of the National Cancer Institute (>250,000 compounds) by pattern
      searching. We split the molecules of this database into fragments to find out
      which fragments exist, how frequent they are, and whether the occurrence of one
      fragment in a molecule is related to the occurrence of another, nonoverlapping
      fragment. It turns out that some fragments and combinations of fragments are so
      frequent that they can be called "chemical cliches". We believe that the fragment
      data can give insight into the chemical space explored so far by synthesis. The
      lists of fragments and their (co-)occurrences can help create novel chemical
      compounds by (i) systematically listing the most popular and therefore most
      easily used substituents and ring systems for synthesizing new compounds, (ii)
      being an easily accessible repository for rarer fragments suitable for lead
      compound optimization, and (iii) pointing out some of the yet unexplored parts of
      chemical space.

PMID- 16562984
TI  - Making "real" molecules in virtual space.
AB  - Predicting "realistic" compounds of given chemical reactions with virtual
      synthesis tools usually requires the manual intervention of experienced chemists
      in the enumeration phase for the selection of appropriate reactants, assignment
      of the corresponding reaction sites, and removal of the unlikely products. To
      automate the virtual synthesis process, we have moved the expertise intensive
      parts from the compound library design phase to the reaction library design
      phase. ChemAxon is building an in silico reaction library containing important
      preparative transformations, where each reaction definition contains a generic
      transformation scheme and additional rules to handle the various starting
      compounds according to the corresponding chemo-, regio-, and stereoselectivity
      issues. Having well designed reaction definitions in hand, our software tool is
      able to generate synthetically feasible compound libraries with minimal effort in
      the enumeration phase.

PMID- 16562985
TI  - Characterizing bitterness: identification of key structural features and
      development of a classification model.
AB  - This work describes the first approach in the development of a comprehensive
      classification method for bitterness of small molecules. The data set comprises
      649 bitter and 13 530 randomly selected molecules from the MDL Drug Data
      Repository (MDDR) which are analyzed by circular fingerprints (MOLPRINT 2D) and
      information-gain feature selection. The feature selection proposes substructural
      features which are statistically correlated to bitterness. Classification is
      performed on the selected features via a naive Bayes classifier. The
      substructural features upon which the classification is based are able to
      discriminate between bitter and random compounds, and thus we propose they are
      also functionally responsible for causing the bitter taste. Such substructures
      include various sugar moieties as well as highly branched carbon scaffolds.
      Cynaropicrine contains a number of the substructural features found to be
      statistically associated with bitterness and thus was correctly predicted to be
      bitter by our model. Alternatively, both promethazine and saccharin contain fewer
      of these substructural features, and thus the bitterness in these compounds was
      not identified. Two different classes of bitter compounds were identified, namely
      those which are larger and contain mainly oxygen and carbon and often sugar
      moieties, and those which are rather smaller and contain additional nitrogen
      and/or sulfur fragments. The classifier is able to predict 72.1% of the bitter
      compounds. Feature selection reduces the number of false-positives while also
      increasing the number of false negatives to 69.5% of bitter compounds correctly
      predicted. Overall, the method presented here presents both one of the largest
      databases of bitter compounds presently available as well as a relatively
      reliable classification method.

PMID- 16562986
TI  - Training similarity measures for specific activities: application to reduced
      graphs.
AB  - Reduced graph representations of chemical structures have been shown to be
      effective in similarity searching applications where they offer comparable
      performance to other 2D descriptors in terms of recall experiments. They have
      also been shown to complement existing descriptors and to offer potential to
      scaffold hop from one chemical series to another. Various methods have been
      developed for quantifying the similarity between reduced graphs including
      fingerprint approaches, graph matching, and an edit distance method. The edit
      distance approach quantifies the degree of similarity of two reduced graphs based
      on the number and type of operations required to convert one graph to the other.
      An attractive feature of the edit distance method is the ability to assign
      different weights to different operations. For example, the mutation of an
      aromatic ring node to an acyclic node may be assigned a higher weight than the
      mutation of an aromatic ring to an aliphatic ring node. In this paper, we
      describe a genetic algorithm (GA) for training the weights of the different edit
      distance operations. The method is applied to specific activity classes extracted
      from the MDDR database to derive activity-class specific weights. The GA-derived
      weights give substantially improved results in recall experiments as compared to
      using weights assigned on intuition. Furthermore, such activity specific weights
      may provide useful structure--activity information for subsequent design efforts.
      In a virtual screening setting when few active compounds are known, it may be
      more useful to have weights that perform well across a variety of different
      activity classes. Thus, the GA is also trained on multiple activity classes
      simultaneously to derive a generalized set of weights. These more generally
      applicable weights also represent a substantial improvement on previous work.

PMID- 16562987
TI  - A knowledge-based weighting approach to ligand-based virtual screening.
AB  - On the basis of the recently introduced reduced graph concept of ErG (extending
      reduced graphs), a straightforward weighting approach to include additional
      (e.g., structural or SAR) knowledge into similarity searching procedures for
      virtual screening (wErG) is proposed. This simple procedure is exemplified with
      three data sets, for which interaction patterns available from X-ray structures
      of native or peptidomimetic ligands with their target protein are used to
      significantly improve retrieval rates of known actives from the MDL Drug Report
      database. The results are compared to those of other virtual screening techniques
      such as Daylight fingerprints, FTrees, UNITY, and various FlexX docking
      protocols. Here, it is shown that wErG exhibits a very good and stable
      performance independent of the target structure. On the basis of this (and the
      fact that ErG retrieves structurally more dissimilar compounds due to its
      potential to perform scaffold-hopping), the combination of wErG and FlexX is
      successfully explored. Overall, wErG is not only an easily applicable weighting
      procedure that efficiently identifies actives in large data sets but it is also
      straightforward to understand for both medicinal and computational chemists and
      can, therefore, be driven by several aspects of project-related knowledge (e.g.,
      X-ray, NMR, SAR, and site-directed mutagenesis) in a very early stage of the hit
      identification process.

PMID- 16562988
TI  - Substructure mining using elaborate chemical representation.
AB  - Substructure mining algorithms are important drug discovery tools since they can
      find substructures that affect physicochemical and biological properties. Current
      methods, however, only consider a part of all chemical information that is
      present within a data set of compounds. Therefore, the overall aim of our study
      was to enable more exhaustive data mining by designing methods that detect all
      substructures of any size, shape, and level of chemical detail. A means of
      chemical representation was developed that uses atomic hierarchies, thus enabling
      substructure mining to consider general and/or highly specific features. As a
      proof-of-concept, the efficient, multipurpose graph mining system Gaston learned
      substructures of any size and shape from a mutagenicity data set that was
      represented in this manner. From these substructures, we extracted a set of only
      six nonredundant, discriminative substructures that represent relevant
      biochemical knowledge. Our results demonstrate the individual and synergistic
      importance of elaborate chemical representation and mining for nonlinear
      substructures. We conclude that the combination of elaborate chemical
      representation and Gaston provides an excellent method for 2D substructure mining
      as this recipe systematically explores all substructures in different levels of
      chemical detail.

PMID- 16562989
TI  - The ROBIA program for predicting organic reactivity.
AB  - A program to predict organic reactions, ROBIA, has been developed. It achieves
      reaction prediction on the basis of coded rules and molecular modeling
      calculations, generating possible transition states, intermediates, and products
      given the starting material and reaction conditions. The program generates all
      possible reaction pathways, on the basis of the selected transformations within
      its database, and evaluates them selecting the most feasible ones. The program
      has been successfully tested against several examples.

PMID- 16562990
TI  - Similarity searching in databases of flexible 3D structures using autocorrelation
      vectors derived from smoothed bounded distance matrices.
AB  - This paper presents an exploratory study of a novel method for flexible 3-D
      similarity searching based on autocorrelation vectors and smoothed bounded
      distance matrices. Although the new approach is unable to outperform an existing
      2-D similarity searching in terms of enrichment factors, it is able to retrieve
      different compounds at a given percentage of the hit-list and so may be a useful
      adjunct to other similarity searching methods.

PMID- 16562991
TI  - SOMA--workflow for small molecule property calculations on a multiplatform
      computing grid.
AB  - We present the concept of the SOMA workflow developed at the Finnish IT Center
      for Science CSC. The SOMA workflow unites multiplatform UNIX/LINUX computing
      resources and third-party software for calculating molecular structure and
      properties. The presented workflow components consist of the computing program
      XML descriptions, the core workflow program Grape, the toolkit for parsing
      program input and output, and the extranet interface. The program Grape and the
      developed XML descriptions of scientific programs allow researchers to link
      molecular modeling software into highly sophisticated computational workflows.
      SOMA collects the calculated data produced by the workflow and stores the
      computed information in the Chemical Markup Language (CML) format. The extranet
      interface is used for user authentication, building of the program interfaces and
      the workflows, and for sorting, filtering, and visualizing the results.

PMID- 16562992
TI  - Collaborative filtering on a family of biological targets.
AB  - Building a QSAR model of a new biological target for which few screening data are
      available is a statistical challenge. However, the new target may be part of a
      bigger family, for which we have more screening data. Collaborative filtering or,
      more generally, multi-task learning, is a machine learning approach that improves
      the generalization performance of an algorithm by using information from related
      tasks as an inductive bias. We use collaborative filtering techniques for
      building predictive models that link multiple targets to multiple examples. The
      more commonalities between the targets, the better the multi-target model that
      can be built. We show an example of a multi-target neural network that can use
      family information to produce a predictive model of an undersampled target. We
      evaluate JRank, a kernel-based method designed for collaborative filtering. We
      show their performance on compound prioritization for an HTS campaign and the
      underlying shared representation between targets. JRank outperformed the neural
      network both in the single- and multi-target models.

PMID- 16562993
TI  - Model selection based on structural similarity-method description and application
      to water solubility prediction.
AB  - A method is introduced that allows one to select, for a given property and
      compound, among several prediction methods the presumably best-performing scheme
      based on prediction errors evaluated for structurally similar compounds. The
      latter are selected through analysis of atom-centered fragments (ACFs) in accord
      with a k nearest neighbor procedure in the two-dimensional structural space. The
      approach is illustrated with seven estimation methods for the water solubility of
      organic compounds and a reference set of 1876 compounds with validated
      experimental values. The discussion includes a comparison with the similarity
      based error correction as an alternative approach to improve the performance of
      prediction methods and an extension that enables an ad hoc specification of the
      application domain.

PMID- 16562994
TI  - Generation and selection of novel estrogen receptor ligands using the de novo
      structure-based design tool, SkelGen.
AB  - A de novo design approach to generating novel estrogen receptor (ER) ligands is
      described. The SkelGen program was used to generate ligands in the active sites
      of seven crystal structures of ERalpha. Seventeen high-scoring, diverse
      structures were selected from the SkelGen output and synthesized without
      introducing any modifications to the structures. Five ligands, four of which are
      novel, showed < or = 25 microM affinity, with the best compound displaying an
      IC50 of 340 nM. SkelGen can, therefore, be a powerful tool for designing active
      molecules.

PMID- 16562995
TI  - In silico prediction of buffer solubility based on quantum-mechanical and HQSAR-
      and topology-based descriptors.
AB  - We present an artificial neural network (ANN) model for the prediction of
      solubility of organic compounds in buffer at pH 6.5, thus mimicking the medium in
      the human gastrointestinal tract. The model was derived from consistently
      performed solubility measurements of about 5000 compounds. Semiempirical VAMP/AM1
      quantum-chemical wave function derived, HQSAR-derived logP, and topology-based
      descriptors were employed after preselection of significant contributors by
      statistical and data mining approaches. Ten ANNs were trained each with 90% as a
      training set and 10% as a test set, and deterministic analysis of prediction
      quality was used in an iterative manner to optimize ANN architecture and
      descriptor space, based on Corina 3D molecular structure and AM1/COSMO single
      point wave function. In production mode, a mean prediction value of the 10 ANNs
      is created, as is a standard deviation based quality parameter. The productive
      ANN based on Corina geometries and AM1/COSMO wave function gives an r2cv of 0.50
      and a root-mean-square error of 0.71 log units, with 87 and 96% of the compounds
      having an error of less than 1 and 1.5 log units, respectively. The model is able
      to predict permanently charged species, e.g. zwitterions or quaternary amines,
      and problematic structures such as tautomers and unresolved diastereomers almost
      as well as neutral compounds.

PMID- 16562996
TI  - Generation of a focused set of GSK compounds biased toward ligand-gated ion
      channel ligands.
AB  - A "data mining" methodology based on substructural analysis and standard 1024
      Daylight fingerprints as descriptors was applied to a set of known antagonists of
      a subfamily of ligand-gated ion channels comprising nicotinic acetylcholine
      receptors (nAChR's), 5-hydroxytryptamine, gamma-amino butyric acid-A, and glycine
      receptors. The derived scoring function was used to generate a focused set that
      was screened for alpha7 nAChR, resulting in the identification of novel alpha7
      ligands easily amenable to chemical modification. Finally, the same scoring
      function was applied retrospectively to other in-house sets screened for the same
      target in the same assay. The results and performance of the method are described
      in detail.

PMID- 16562997
TI  - Molecular field extrema as descriptors of biological activity: definition and
      validation.
AB  - The paper describes the generation of four types of three-dimensional molecular
      field descriptors or 'field points' as extrema of electrostatic, steric, and
      hydrophobic fields. These field points are used to define the properties
      necessary for a molecule to bind in a characteristic way into a specified active
      site. The hypothesis is that compounds showing a similar field point pattern are
      likely to bind at the same target site regardless of structure. The methodology
      to test this idea is illustrated using HIV NNRTI and thrombin ligands and
      validated across seven other targets. From the in silico comparisons of field
      point overlays, the experimentally observed binding poses of these ligands in
      their respective sites can be reproduced from pairwise comparisons.

PMID- 16562998
TI  - The quest for bioisosteric replacements.
AB  - To help advance drug discovery projects, a new and validated search method is
      presented by which potential bioisosteric replacements can be retrieved from a
      database of more than 700,000 structural fragments. The heart of the search
      method is an optimized topological pharmacophore fingerprint which describes each
      fragment as a combination of attachment points, hydrogen bond donors and
      acceptors, hydrophobic centers, conjugated atoms, and non-hydrogen atoms. In the
      fingerprint the influence of the attachment point is enhanced by giving it extra
      weight relative to the other descriptors. The Euclidean distance has proven to be
      the optimum distance measure to compare the fingerprints in a database search.
      The performance of the pharmacophore fingerprint based search method has been
      validated using more than 2200 bioisosteric fragment pairs extracted in an
      unbiased procedure from the BIOSTER database. The true bioisosteric pairs have
      been compared with pairs of random fragments originating from the WDI database.
      Normalized by the standard deviation of the random pairs distance distributions,
      an excellent separation of true pairs from random pairs was obtained for R-group
      fragments (2.2 standard deviation units) as well as for linkers (2.6 units) and
      cores (2.6 units). The bioisoster search method has been implemented as an
      intranet application called IBIS and is now routinely used by Organon
      researchers.

PMID- 16562999
TI  - Knowledge-based interaction fingerprint scoring: a simple method for improving
      the effectiveness of fast scoring functions.
AB  - A new method for the postprocessing of docking outputs has been developed, based
      on encoding putative 3D binding modes (docking solutions) as ligand-protein
      interactions into simple bit strings, a method analogous to the structural
      interaction fingerprint. Instead of employing traditional scoring functions, the
      method uses a series of new, knowledge-based scores derived from the similarity
      of the bit strings for each docking solution to that of a known reference binding
      mode. A GOLD docking study was carried out using the Bissantz estrogen receptor
      antagonist set along with the new scoring method. Superior recovery rates, with
      up to 2-fold enrichments, were observed when the new knowledge-based scoring was
      compared to the GOLD fitness score. In addition, top ranking sets of molecules
      (actives and potential actives or decoys) were structurally diverse with low
      molecular weights and structural complexities. Principal component analysis and
      clustering of the fingerprints permits the easy separation of active from
      inactive binding modes and the visualization of diverse binding modes.

PMID- 16563000
TI  - Flux (1): a virtual synthesis scheme for fragment-based de novo design.
AB  - It is demonstrated that the fragmentation of druglike molecules by applying
      simplistic pseudo-retrosynthesis results in a stock of chemically meaningful
      building blocks for de novo molecule generation. A stochastic search algorithm in
      conjunction with ligand-based similarity scoring (Flux: fragment-based ligand
      builder reaxions) facilitated the generation of new molecules using a single
      known reference compound as a template. This molecule assembly method is
      applicable in the absence of receptor-structure information. In a case study, we
      used imantinib (Gleevec) and a Factor Xa inhibitor as the reference structures.
      The algorithm succeeded in redesigning the templates from scratch and suggested
      several alternative molecular structures. The resulting designed molecules were
      chemically reasonable and contained essential substructure motifs. A comparison
      of molecular descriptors suggests that holographic descriptors might be
      advantageous over binary fingerprints for ligand-based de novo design.

PMID- 16563001
TI  - Structure-based pharmacophore design and virtual screening for novel angiotensin
      converting enzyme 2 inhibitors.
AB  - The metallopeptidase Angiotensin Converting Enzyme (ACE) is an important drug
      target for the treatment of hypertension, heart, kidney, and lung disease.
      Recently, a close and unique human ACE homologue termed ACE2 has been identified
      and found to be an interesting new cardiorenal disease target. With the recently
      resolved inhibitor-bound ACE2 crystal structure available, we have attempted a
      structure-based approach to identify novel potent and selective inhibitors.
      Computational approaches focus on pharmacophore-based virtual screening of large
      compound databases. Selectivity was ensured by initial screening for ACE
      inhibitors within an internal database and the Derwent World Drug Index, which
      could be reduced to zero false positives and 0.1% hit rate, respectively. An
      average hit reduction of 0.44% was achieved with a five feature hypothesis,
      searching approximately 3.8 million compounds from various commercial databases.
      Seventeen compounds were selected based on high fit values as well as diverse
      structure and subjected to experimental validation in a bioassay. We show that
      all compounds displayed an inhibitory effect on ACE2 activity, the six most
      promising candidates exhibiting IC50 values in the range of 62-179 microM.

PMID- 16563002
TI  - sc-PDB: an annotated database of druggable binding sites from the Protein Data
      Bank.
AB  - The sc-PDB is a collection of 6 415 three-dimensional structures of binding sites
      found in the Protein Data Bank (PDB). Binding sites were extracted from all high
      resolution crystal structures in which a complex between a protein cavity and a
      small-molecular-weight ligand could be identified. Importantly, ligands are
      considered from a pharmacological and not a structural point of view. Therefore,
      solvents, detergents, and most metal ions are not stored in the sc-PDB. Ligands
      are classified into four main categories: nucleotides (< 4-mer), peptides (< 9
      mer), cofactors, and organic compounds. The corresponding binding site is formed
      by all protein residues (including amino acids, cofactors, and important metal
      ions) with at least one atom within 6.5 angstroms of any ligand atom. The
      database was carefully annotated by browsing several protein databases (PDB,
      UniProt, and GO) and storing, for every sc-PDB entry, the following features:
      protein name, function, source, domain and mutations, ligand name, and structure.
      The repository of ligands has also been archived by diversity analysis of
      molecular scaffolds, and several chemoinformatics descriptors were computed to
      better understand the chemical space covered by stored ligands. The sc-PDB may be
      used for several purposes: (i) screening a collection of binding sites for
      predicting the most likely target(s) of any ligand, (ii) analyzing the molecular
      similarity between different cavities, and (iii) deriving rules that describe the
      relationship between ligand pharmacophoric points and active-site properties. The
      database is periodically updated and accessible on the web at http://bioinfo
      pharma.u-strasbg.fr/scPDB/.

PMID- 16563003
TI  - Using pharmacophore models to gain insight into structural binding and virtual
      screening: an application study with CDK2 and human DHFR.
AB  - This study provides results from two case studies involving the application of
      the HypoGenRefine algorithm within Catalyst for the automated generation of
      excluded volume from ligand information alone. A limitation of pharmacophore
      feature hypothesis alone is that activity prediction is based purely on the
      presence and arrangement of pharmacophoric features; steric effects remained
      unaccounted. Recently reported studies have illustrated the usefulness of
      combining excluded volumes to the pharmacophore models. In general, these
      excluded volumes attempt to penalize molecules occupying steric regions that are
      not occupied by active molecules. The HypoGenRefine algorithm in Catalyst
      accounts for steric effects on activity, based on the targeted addition of
      excluded volume features to the pharmacophores. The automated inclusion of
      excluded volumes to pharmacophore models has been applied to two systems: CDK2
      and human DHFR. These studies are used as examples to illustrate how ligands
      could bind in the protein active site with respect to allowed and disallowed
      binding regions. Additionally, automated refinement of the pharmacophore with
      these excluded volume features provides a more selective model to reduce false
      positives and a better enrichment rate in virtual screening.

PMID- 16563004
TI  - A searchable database for comparing protein-ligand binding sites for the analysis
      of structure-function relationships.
AB  - The rapid expansion of structural information for protein-ligand binding sites is
      potentially an important source of information in structure-based drug design and
      in understanding ligand cross reactivity and toxicity. We have developed a large
      database of ligand binding sites extracted automatically from the Protein Data
      Bank. This has been combined with a method for calculating binding site
      similarity based on geometric hashing to create a relational database for the
      retrieval of site similarity and binding site superposition. It contains an all
      against-all comparison of binding sites and holds known protein-ligand binding
      sites, which are made accessible to data mining. Here we demonstrate its utility
      in two structure-based applications: in determining site similarity and in aiding
      the derivation of a receptor-based pharmacophore model. The database is available
      from http://www.bioinformatics.leeds.ac.uk/sb/.

PMID- 16563005
TI  - Structural DNA profiles: single sequence queries.
AB  - Structural DNA profiles use the structural properties of the constituent octamers
      either to observe any characteristics of a single sequence that are unusual (a
      single sequence query) or to visualize a pattern common to a set of sequences (a
      multiple sequence query). They are an aid in understanding structural reasons for
      functional DNA activity. Profiles that answer single sequence queries are
      introduced and Profile Manager (a software application developed to automate
      profile generation) is presented. Two sequences that are similar by their
      nucleotide composition but are known to be very different by structure are
      analyzed, resulting in useful illustrations that agree with the experimental
      nuclear magnetic resonance structures.

PMID- 16563006
TI  - Genomic data analysis using DNA structure: an analysis of conserved nongenic
      sequences and ultraconserved elements.
AB  - Recent comparative studies of the human and mouse genomes have revealed sets of
      conserved nongenic sequences (CNGs) and sets of ultraconserved elements (UCEs).
      Both sets of sequences, which exhibit extremely high levels of conservation,
      extend over hundreds of bases and have no known function. Since there is no
      detectable sequence homology between paralogous CNGs or UCEs in either of the
      species, an alignment-free technique is needed for their analysis. We have
      previously compiled a database of the structural properties of all 32,896 unique
      DNA octamers, including information on stability, the minimum energy
      conformation, and flexibility. We have used Fourier techniques to analyze the
      UCEs and CNGs in terms of their octamer structural properties, to reveal
      structural correlations which may indicate possible functions for some of these
      sequences.

PMID- 16563007
TI  - VET: a tool for reaction plausibility checking.
AB  - Production of chemical reaction databases is a multistep process, with the
      possibility of errors at each of these steps. VET is a tool developed to trap
      errors in the chemical reactions identified as a part of this process. VET has
      been designed to minimize the acceptance of incorrect reactions, while still
      supporting various common practices in reaction depiction, including unbalanced
      reactions, suppressed components, and reactions with alternative products. We
      discuss the assumptions made in its construction, a general overview of its
      structure, and some performance characteristics.

PMID- 16563008
TI  - SciFinder Scholar 2006: an empirical analysis of research topic query processing.
AB  - Topical search queries in SciFinder Scholar are processed through an extensive
      set of natural language processing algorithms that greatly enhance the relevance
      and comprehensiveness of the search results. Little detailed documentation on
      these algorithms has been published. However, a careful examination of the
      highlighted hit terms coupled with a comparison of results from small variations
      in query language reveal much additional, useful information about these
      algorithms. An understanding of how these algorithms work can lead to better
      search results and explain many unexpected results, including differing hit
      counts for singular versus plural query words and phrases.

PMID- 16563009
TI  - Spec2D: a structure elucidation system based on 1H NMR and H-H COSY spectra in
      organic chemistry.
AB  - A system for structure elucidation based on proton NMR spectra has been
      developed. The system, named Spec2D (system for spectra from 2D-NMR),
      incorporates 1H NMR and H-H correlation spectroscopy (COSY) spectral information
      obtained from 2D-NMR experiments. 2D-NMR is important for the structure
      elucidation because it provides information about the relationships among
      differently situated protons in the structures of unknown compounds. The system
      uses the concepts of molecular graphs. The improved representation of
      substructures as well as several novel algorithms for structure generation have
      been devised to solve the combinatorial problem and to reduce the processing
      time. Spec2D consists of a knowledge base, an analysis module, and a candidate
      structure generator module. Spec2D proposes candidate structures from only 1H NMR
      and H-H COSY spectral information of an unknown compound without any 13C NMR
      spectral or structural information, such as molecular formulas. Spec2D has the
      capability to propose the "new" structure of an unknown compound, if the
      corresponding substructures are included in the knowledge base.

PMID- 16563010
TI  - What do we know about C28H14 and C30H14 benzenoid hydrocarbons and their
      evolution to related polymer strips?
AB  - While critically reviewing the current status of what is known about C28H14 and
      C30H14 benzenoid isomers, which are ubiquitous pyrolytic constituents, some new
      insights will be presented. Representative isomers belonging to these benzenoid
      hydrocarbons are at the crossroads to homologous series that extend to infinite
      polymer strips that have been the object of numerous molecular modeling studies.
      The goal of these studies is to understand their potential electronic properties
      for material science applications. Along the way, some prior numerical results
      are supplemented.

PMID- 16563011
TI  - The electronic structures and properties of open-ended and capped carbon
      nanoneedles.
AB  - The existence of a family of very thin carbon needlelike nanostructures is
      predicted: the geometry and stability of several carbon nanoneedles (CNNs) formed
      by C4 and C6 units have been studied by quantum chemistry computational modeling
      methods. The structures of carbon nanoneedles are tighter than even the smallest
      single wall nanotubes (SWNTs) based on (4, 0) naphthacene. The electronic
      properties, energetic stability of geometrical structures with various terminal
      units are investigated. The relatively large band gaps, the strong bonding, and
      additional orbital interactions within the C4 rings and between the C4 layers
      make the H4(C4)(n)H4 type molecules nonmetallic. We have found indications that
      if the CNN (3, 0) structures are very long (in the limit of infinite-length),
      then they are likely to have semiconducting properties and could possibly be used
      as actual semiconductors. The studied families of CNNs can be considered as
      carbon nanostructures with unique structural and chemical properties and with
      possible potential for unusual electronic properties, with likely practical
      applications as nanomaterials and nanostructure devices.

PMID- 16563013
TI  - An atlas of forecasted molecular data. 2. Vibration frequencies of main-group and
      transition-metal neutral gas-phase diatomic molecules in the ground state.
AB  - This atlas of diatomic-molecular vibration frequencies parallels the previously
      offered Atlas of Internuclear Separations. The Atlas was produced by mining the
      data from Huber and Herzberg and training neural network software to forecast new
      data. New protocols were employed with the powerful software, which was
      originally designed for forecasting the financial markets. The Atlas presents
      1920 additional vibration frequencies for use until critical tables are available
      to fill the needs more precisely. The precision of the predictions is
      characterized by the average fractional 1% confidence limit, that is, 10.66%. The
      accuracies of the predictions are determined in two ways. First, 221 of the 224
      Huber and Herzberg data values used for training and validation fall within the
      prediction confidence limits or fall outside by less than 10% of the Huber and
      Herzberg values, and 181 values agree (within the limits). Second, 87 of 101
      comparison data values, consisting of literature data and some additional Huber
      and Herzberg values, fall within the prediction confidence limits or fall outside
      by less than half the prediction values, and 44 of the 101 values agree (within
      the limits).

PMID- 16563012
TI  - Benchmarking of linear and nonlinear approaches for quantitative structure
      property relationship studies of metal complexation with ionophores.
AB  - A benchmark of several popular methods, Associative Neural Networks (ANN),
      Support Vector Machines (SVM), k Nearest Neighbors (kNN), Maximal Margin Linear
      Programming (MMLP), Radial Basis Function Neural Network (RBFNN), and Multiple
      Linear Regression (MLR), is reported for quantitative-structure property
      relationships (QSPR) of stability constants logK1 for the 1:1 (M:L) and logbeta2
      for 1:2 complexes of metal cations Ag+ and Eu3+ with diverse sets of organic
      molecules in water at 298 K and ionic strength 0.1 M. The methods were tested on
      three types of descriptors: molecular descriptors including E-state values,
      counts of atoms determined for E-state atom types, and substructural molecular
      fragments (SMF). Comparison of the models was performed using a 5-fold external
      cross-validation procedure. Robust statistical tests (bootstrap and Kolmogorov
      Smirnov statistics) were employed to evaluate the significance of calculated
      models. The Wilcoxon signed-rank test was used to compare the performance of
      methods. Individual structure-complexation property models obtained with
      nonlinear methods demonstrated a significantly better performance than the models
      built using multilinear regression analysis (MLRA). However, the averaging of
      several MLRA models based on SMF descriptors provided as good of a prediction as
      the most efficient nonlinear techniques. Support Vector Machines and Associative
      Neural Networks contributed in the largest number of significant models. Models
      based on fragments (SMF descriptors and E-state counts) had higher prediction
      ability than those based on E-state indices. The use of SMF descriptors and E
      state counts provided similar results, whereas E-state indices lead to less
      significant models. The current study illustrates the difficulties of
      quantitative comparison of different methods: conclusions based only on one data
      set without appropriate statistical tests could be wrong.

PMID- 16563014
TI  - Designing novel polymers with targeted properties using the signature molecular
      descriptor.
AB  - A method for solving the inverse quantitative structure-property relationship
      (QSPR) problem is presented which facilitates the design of novel polymers with
      targeted properties. Here, we demonstrate the efficacy of the approach using the
      targeted design of polymers exhibiting a desired glass transition temperature,
      heat capacity, and density. We present novel QSPRs based on the signature
      molecular descriptor capable of predicting glass transition temperature, heat
      capacity, density, molar volume, and cohesive energies of linear homopolymers
      with cross-validation squared correlation coefficients ranging between 0.81 and
      0.95. Using these QSPRs, we show how the inverse problem can be solved to design
      poly(N-methyl hexamethylene sebacamide) despite the fact that the polymer was
      used not used in the training of this model.

PMID- 16563015
TI  - A novel search engine for virtual screening of very large databases.
AB  - Virtual screening of large chemical databases using the structure of the receptor
      can be computationally very demanding. We present a novel strategy that combines
      exhaustive similarity searches directly in SMILES format with the docking of
      flexible ligands, whose 3D structure is generated on the fly from the SMILES
      representation. Our strategy makes use of the recently developed LINGO tools to
      extract implicit chemical information from SMILES strings and integrates LINGO
      similarities into a pseudo-evolutionary algorithm. The algorithm represents a
      combination of a fast target-independent similarity method with a slower but
      information richer target-focused method. A virtual search of FactorXa ligands
      provided 62% of the potential hits after docking only 6.5% of a database of
      nearly 1 million molecules. The set of solutions showed good diversity,
      indicating that the method shows good scaffold hopping capabilities.

PMID- 16563017
TI  - A comparative study on the application of hierarchical-agglomerative clustering
      approaches to organize outputs of reiterated docking runs.
AB  - Reiterated runs of standard docking protocols usually provide a collection of
      possible binding modes rather than pinpoint a single solution. Usually, this
      ensemble is then ranked by means of an energy-based scoring function. However,
      since many degrees of approximation have to be introduced in the computation of
      the binding free energy, scoring functions cannot always rank the experimental
      pose among the top scorers. Cluster analysis might help to overcome this limit,
      provided that data clusterability has been earlier assessed. In this paper,
      first, we present a modified version of a test earlier developed by Hopkins to
      assess whether or not docking outputs show the natural tendency to be grouped in
      clusters. Then, we report the results of a comparative study on the application
      of different hierarchical-agglomerative cluster rules to partition docking
      outputs. The rule that was able to best manage the observed data was finally
      applied to the whole ensemble of poses collected from several docking tools. The
      combination of the average linkage rule with the cutting function developed by
      Sutcliffe and co-workers turned out to be an approach that meets all of the
      criteria required for a robust clustering protocol. Furthermore, a consensus
      clustering allowed us to identify the pose closest to the experimental one within
      a statistically significant cluster, whose number was always of few units.

PMID- 16563016
TI  - Chemometric analysis of ligand receptor complementarity: identifying
      Complementary Ligands Based on Receptor Information (CoLiBRI).
AB  - We have developed a novel structure-based chemoinformatics approach to search for
      Complimentary Ligands Based on Receptor Information (CoLiBRI). CoLiBRI is based
      on the representation of both receptor binding sites and their respective ligands
      in a space of universal chemical descriptors. The binding site atoms involved in
      the interaction with ligands are identified by the means of a computational
      geometry technique known as Delaunay tessellation as applied to X-ray
      characterized ligand-receptor complexes. TAE/RECON multiple chemical descriptors
      are calculated independently for each ligand as well as for its active site
      atoms. The representation of both ligands and active sites using chemical
      descriptors allows the application of well-known chemometric techniques in order
      to correlate chemical similarities between active sites and their respective
      ligands. We have established a protocol to map patterns of nearest neighbor
      active site vectors in a multidimensional TAE/RECON space onto those of their
      complementary ligands and vice versa. This protocol affords the prediction of a
      virtual complementary ligand vector in the ligand chemical space from the
      position of a known active site vector. This prediction is followed by chemical
      similarity calculations between this virtual ligand vector and those calculated
      for molecules in a chemical database to identify real compounds most similar to
      the virtual ligand. Consequently, the knowledge of the receptor active site
      structure affords straightforward and efficient identification of its
      complementary ligands in large databases of chemical compounds using rapid
      chemical similarity searches. Conversely, starting from the ligand chemical
      structure, one may identify possible complementary receptor cavities as well. We
      have applied the CoLiBRI approach to a data set of 800 X-ray characterized ligand
      receptor complexes in the PDBbind database. Using a k nearest neighbor (kNN)
      pattern recognition approach and variable selection, we have shown that knowledge
      of the active site structure affords identification of its complimentary ligand
      among the top 1% of a large chemical database in over 90% of all test active
      sites when a binding site of the same protein family was present in the training
      set. In the case where test receptors are highly dissimilar and not present among
      the receptor families in the training set, the prediction accuracy is decreased;
      however, CoLiBRI was still able to quickly eliminate 75% of the chemical database
      as improbable ligands. CoLiBRI affords rapid prefiltering of a large chemical
      database to eliminate compounds that have little chance of binding to a receptor
      active site.

PMID- 16563018
TI  - Peak alignment of urine NMR spectra using fuzzy warping.
AB  - Proton nuclear magnetic resonance (1H NMR) spectroscopic analysis of mixtures has
      been used extensively for a variety of applications ranging from the analysis of
      plant extracts, wine, and food to the evaluation of toxicity in animals. For
      example, NMR analysis of urine samples has been used extensively for biomarker
      discovery and, more simply, for the construction of classification models of
      toxicity, disease, and biochemical phenotype. However, NMR spectra of complex
      mixtures typically show unwanted local peak shifts caused by matrix and
      instrument variability, which must be compensated for prior to statistical
      analysis and interpretation of the data. One approach is to align the spectral
      peaks across the data set. An efficient and fast warping algorithm is required as
      the signals typically contain ca. 32,000-64,000 data points and there can be
      several thousand spectra in a data set. As demonstrated in our study, the
      iterative fuzzy warping algorithm fulfills these requirements and can be used on
      line for an alignment of the NMR spectra. Correlation coefficients between the
      aligned and target spectra are used as the evaluation function for the algorithm,
      and its performance is compared with those of other published warping methods.

PMID- 16563019
TI  - Spectrophotometric determination and computational evaluation of the rates of
      hydrolysis of 9-amino-substituted acridines.
AB  - Aminoacridines have a long history in the drug and dye industries and display a
      wide range of biological and physical properties. Despite the historical
      relevance of 9-aminoacridines, there have been few studies investigating their
      stability. 9-Aminoacridines are known to hydrolyze at the C9-N15 bond, yielding
      acridones. In this study, the pH-dependent hydrolysis rates of a series of 9
      substituted aminoacridines are investigated. In addition, ground-state physical
      properties of the compounds are determined using ab initio quantum mechanics
      calculations to gain insight into the forces that drive hydrolysis. An analysis
      of the bond orders, bond dissociation energies, and conformational energies show
      that the rate of hydrolysis depends on two main factors: delocalization across
      the C9-N15 bond and steric effects. The computational results are applied to
      explain the change in experimental rates of hydrolysis going from primary to
      secondary and to tertiary substituted 9-aminoacridines. In the case of tertiary
      substituted amines, the calculations indicate the C9-N15 bond is forced into a
      more gauche-like conformation, greatly diminishing delocalization (as shown by
      reductions in bond orders and bond energy), which leads to rapid hydrolysis. A
      model of intramolecular hydrogen bonding is also presented, which explains the
      increased rate of hydrolysis observed for highly substituted compounds under
      acidic conditions.

PMID- 16563020
TI  - Development of novel statistical potentials describing cation-pi interactions in
      proteins and comparison with semiempirical and quantum chemistry approaches.
AB  - Novel statistical potentials derived from known protein structures are presented.
      They are designed to describe cation-pi and amino-pi interactions between a
      positively charged amino acid or an amino acid carrying a partially charged amino
      group and an aromatic moiety. These potentials are based on the propensity of
      residue types to be separated by a certain spatial distance or to have a given
      relative orientation. Several such potentials, describing different kinds of
      correlations between residue types, distances, and orientations, are derived and
      combined in a way that maximizes their information content and minimizes their
      redundancy. To test the ability of these potentials to describe cation-pi and
      amino-pi systems, we compare their energies with those computed with the CHARMM
      molecular mechanics force field and with quantum chemistry calculations at the
      Hartree-Fock level (HF) and at the second order of the Moller-Plesset
      perturbation theory (MP2). The latter calculations are performed in the gas phase
      and in acetone, in order to mimic the average dielectric constant of protein
      environments. The energies computed with the best of our statistical potentials
      and with gas-phase HF or MP2 show correlation coefficients up to 0.96 when
      considering one side-chain degree of freedom in the statistical potentials and up
      to 0.94 when using a totally simplified model excluding all side-chain degrees of
      freedom. These potentials perform as well as, or better than, the CHARMM
      molecular mechanics force field that uses a much more detailed protein
      representation. The good performance of our cation-pi statistical potentials
      suggests their utility in protein structure and stability prediction and in
      protein design.

PMID- 16563021
TI  - Structure-fate relationships of organic chemicals derived from the software
      packages E4CHEM and WHASSE.
AB  - A risk assessment of chemicals is to be performed on the basis of the model
      EUSES, developed by the Commission of the European Union. The model package
      E4CHEM (Exposure Estimation for Potentially Ecotoxic Environmental Chemicals),
      developed in 1984-1992, is presented and applied in this paper as a model which
      allows a model-supported evaluation of chemicals. E4CHEM consequently does not
      have the wide applicability and technical comfort of the more recently developed
      model EUSES. The simulation models of E4CHEM characterize the chemical behavior
      in the environment by many aspects. Hence, there is a need to condense all of
      these aspects to get a clear impression of what will be the fate of the
      chemicals. Starting with the already published concept of exposure maps, we will
      discuss how partial orders may be helpful in establishing generalized structure
      fate relationships. The software WHASSE is applied.

PMID- 16563022
TI  - Fully automated flexible docking of ligands into flexible synthetic receptors
      using forward and inverse docking strategies.
AB  - The prediction of the structure of host-guest complexes is one of the most
      challenging problems in supramolecular chemistry. Usual procedures for docking of
      ligands into receptors do not take full conformational freedom of the host
      molecule into account. We describe and apply a new docking approach which
      performs a conformational sampling of the host and then sequentially docks the
      ligand into all receptor conformers using the incremental construction technique
      of the FlexX software platform. The applicability of this approach is validated
      on a set of host-guest complexes with known crystal structure. Moreover, we
      demonstrate that due to the interchangeability of the roles of host and guest,
      the docking process can be inverted. In this inverse docking mode, the receptor
      molecule is docked around its ligand. For all investigated test cases, the
      predicted structures are in good agreement with the experiment for both normal
      (forward) and inverse docking. Since the ligand is often smaller than the
      receptor and, thus, its conformational space is more restricted, the inverse
      docking approach leads in most cases to considerable speed-up. By having the
      choice between two alternative docking directions, the application range of the
      method is significantly extended. Finally, an important result of this study is
      the suitability of the simple energy function used here for structure prediction
      of complexes in organic media.

PMID- 16563023
TI  - Adding value to crystallographically-derived knowledge bases.
AB  - A protocol for the partially automated computational investigation of crystal
      structure geometries of transition-metal complexes with unusual/outlier
      structural features has been developed for application in an e-science context.
      This protocol not only is envisaged as a part of knowledge base software packages
      such as Mogul but can also be used to further analyze the results of database
      searches. The issues arising from automating the initial input generation and DFT
      optimization of complexes have been examined and a procedure for extracting
      additional knowledge "value" from the computational results is described.
      Potential problems/weaknesses arising from the choice of computational approach
      and from errors in the crystal structure refinement are discussed. A range of
      likely outcomes of applying this protocol to database mining results is
      illustrated, with representative examples identified for tetracoordinate
      transition-metal complexes and ligand fragments (terminal chloride, monodentate
      phosphorus(III), and primary amine ligands) with unusual metal-ligand bond
      lengths.

PMID- 16563024
TI  - QSPR correlation of melting point for drug compounds based on different sources
      of molecular descriptors.
AB  - Five linear QSPR models for melting points (MP) of drug-like compounds are
      developed based on three different packages for molecular descriptor generation
      and a combined set of all descriptors. A data set of 323 gaseous, liquid, and
      solid compounds was used for this study. Two models from the combined set of
      descriptors based on stepwise regression and genetic algorithm (GA) descriptor
      selection methods have acceptable prediction abilities. The statistical results
      of these models are r2 = 0.673 and root-mean-square error (RMSE) of 40.4 degrees
      C for stepwise regression-based quantitative structure-property relationships
      (QSPRs) and r2 = 0.660 and RMSE of 41.1 degrees C for GA-based QSPRs.
      Interpretation of descriptors of all models showed a strong correlation of
      hydrogen bonding and molecular complexity with melting points of drug-like
      compounds.

PMID- 16563025
TI  - Binding of warfarin influences the acid-base equilibrium of H242 in sudlow site I
      of human serum albumin.
AB  - Sudlow Site I of human serum albumin (HSA) is located in subdomain IIA of the
      protein and serves as a binding cavity for a variety of ligands. In this study,
      the binding of warfarin (W) is examined using computational techniques and
      isothermal titration calorimetry (ITC). The structure of the docked warfarin
      anion (W-) to Site I is similar to that revealed by X-ray crystallography, with a
      calculated binding constant of 5.8 x 10(5) M(-1). ITC experiments (pH 7.13 and I
      = 0.1) carried out in three different buffers (MOPs, phosphate and Tris) reveal
      binding of W- is accompanied by uptake of 0.30+/-0.02 protons from the solvent.
      This measurement suggests that the binding of W- is stabilized by an ion-pair
      interaction between protonated H242 and the phenoxide group of W-.

PMID- 16563026
TI  - Reference limits for erythema-effective UV doses.
AB  - Diagnostic phototesting, including the determination of the minimal erythema dose
      (MED), is a useful procedure to detect abnormal sensitivity to UV radiation. We
      aimed to estimate the reference limits (RLs) of the MED in a reasonably large
      reference sample of white individuals. Skin phototypes and MED values for
      broadband UVB and for UVA were determined in 461 white subjects. When
      appropriate, the 95% reference intervals, including the 0.025 fractile and 0.975
      fractile, were computed for the MED-UVB reference values (by means of parametric
      methods) and the MED-UVA reference values (by means of nonparametric methods).
      MED data were also converted to standard erythema doses (SEDs). As described
      elsewhere we observed a considerable overlap of MED values for all skin
      phototypes and confirmed that age and sex do not substantially influence the MED.
      The lower RLs observed for MED-UVB were 33 mJ cm(-2) (0.5 SEDs) and for MED-UVA
      12.6 mJ cm(-2) (1.2 SEDs). The MED and SED findings from this investigation may
      serve as reference data for white individuals and give support to the clinician
      in differentiating between normal and pathologically abnormal photosensitivity.
      Although the MED data given here are limited to the phototest device used in the
      present study, the SED results establish comparability between our data and
      phototest results obtained from laboratories using different UV sources.

PMID- 16563027
TI  - The meth epidemic: its effect on children and communities.

PMID- 16563028
TI  - Methamphetamine: putting the brakes on speed.
AB  - In only recent history, illicit use of methamphetamine, once isolated to urban
      areas on the West Coast, has spread into rural areas of the Midwest and southern
      United States. Although past and current methamphetamine legislation has
      increased penalties for methamphetamine manufacturers and tightened restrictions
      on sales of known precursors, the problem still persists. In fact, a 2004 survey
      indicates that an alarming 6.2% of high school seniors have tried
      methamphetamine. A number of biological, genetic, and environmental factors
      influence children's and adolescents' paths to substance abuse. Nurses should
      recognize the symptoms of methamphetamine abuse, which include agitation;
      aggressive behavior; rapid mood swings; hypertension; tachycardia; and eventually
      lesion-marked skin, clinical depression, and paranoid psychosis. Treatment for
      methamphetamine addiction includes behavioral therapy. Research on pharmacologic
      therapy is lacking. Educating youth on methamphetamine prevention appears to be
      the best approach to curb the spreading use of this addictive and deadly drug.

PMID- 16563029
TI  - Stoma care in the school setting.
AB  - An ostomy is an artificial opening in the body for the purpose of eliminating
      excretions from a working organ or for providing nourishment. Artificial openings
      may be from the stomach, intestine, urinary bladder, kidney, or trachea. The
      stoma is the terminal end of the ostomy, or the opening that is visible on the
      surface of the skin. This article will discuss stoma creation and the care of a
      stoma, as well as the complications and effects of living with one. Although the
      focus of this article is urinary stomas, the care is similar for all types. It is
      imperative that all care providers understand stoma care and potential problems
      that may arise. There are ongoing issues of quality of life for children with
      stomas, including body image and peer reaction. School nurses are in a unique
      position to educate children and families on the proper care of a stoma, to
      recognize potential complication, and to educate staff and student peers.

PMID- 16563030
TI  - Teaching children about mental health and illness: a school nurse health
      education program.
AB  - A mental health education program designed by school nurses for children ages 10-
      12 was developed in 2000-2001 and expanded with broader distribution in 2004
      2005. Six classroom sessions, each 45 minutes in length, provided information and
      activities to increase children's awareness of mental health and illness.
      Education program content included facts about the brain's connection to mental
      health, information about healthy ways to manage stress, resources and activities
      to promote mental health, common mental health problems experienced by children,
      and how to seek help for mental health problems. Classes included a combination
      of didactic presentation and open discussion, encouraging students to ask
      questions and allowing the school nurse to correct misinformation. Analysis of
      pre- and posttests from 370 elementary and middle school students revealed
      statistically significant improvements in their knowledge of mental health and
      mental illness.

PMID- 16563031
TI  - Adolescent immunization: challenges and opportunities.
AB  - Immunization is one of the greatest public health achievements of the past
      century. Vaccines are responsible for the worldwide eradication of smallpox, the
      elimination of polio in the western hemisphere, and most recently the elimination
      of rubella as a public health threat in the United States. Childhood vaccination
      rates are at an all-time high, but immunization falls off dramatically during
      adolescence (ages 11-19). With increased attention being paid to adolescent
      health and the new vaccines available for adolescents, efforts to increase
      adolescent immunization rates are moving to the forefront. Improving adolescent
      immunization rates requires advocacy on the part of all health professionals.
      School nurses, whose mission is to enhance the well-being of adolescents, are in
      a unique position to work with students, parents, and local health professionals
      to improve the adolescent immunization rate.

PMID- 16563032
TI  - NANDA diagnoses, NIC interventions, and NOC outcomes used in an electronic health
      record with elementary school children.
AB  - This is a report of a secondary analysis of data from a published quasi
      experimental feasibility study of the effects of implementing diagnoses from
      North American Nursing Diagnosis Association International, interventions from
      the Nursing Interventions Classification, and outcomes from the Nursing Outcomes
      Classification (referred to as NNN) on nurses' power and children's health
      outcomes. For this study, the NNN terms that were frequently used by nurses in
      the original study were identified through the nurses' printed reports of health
      related visits (N = 766) with 103 New York City children in the 4th and 5th
      grades in six schools. The findings indicate that a large majority of nurses'
      efforts were focused on health promotion and management of risk states. Health
      problems such as pain and ineffective airway clearance were identified and were
      treated when present. Findings from this study can be combined with findings from
      previous studies to identify the diagnoses, interventions, and outcomes that are
      relevant for school settings. Use of the relevant NNN terms will provide data to
      support evidenced-based school nursing practice, education of school nurses,
      development of policies, and communication of the value of school nursing
      practice to stakeholders.

PMID- 16563033
TI  - Changes in medications administered in schools.
AB  - The purpose of this descriptive, cross-sectional study was to determine if there
      have been changes in the type and number of attention deficit/hyperactivity
      disorder (AD/HD) medications administered in schools since the introduction of
      long-acting stimulants. A survey was sent to 1,000 school nurses randomly
      selected from the National Association of School Nurses membership, with 339
      returned (34%). Between 2000 and 2003 the proportion of students receiving any
      prescription medication (2.9/100 vs. 1.0/100), methylphenidate (1.2 vs. 0.2), or
      amphetamine/dextroamphetamine (0.3/100 vs. 0.1/100) was significantly reduced ( p
      < .0001). High school students took fewer prescription ( p < .0001) and AD/HD
      medications ( p < .0001), but more nonprescription medications than other
      students. A total of 163 different prescription medications and 28
      nonprescription medications were administered during the typical school day. This
      study suggests that the use of long-acting stimulants has significantly reduced
      the number of prescription medications administered in schools. This reduction
      has been accompanied by a dramatic increase in the range of medications
      administered, making the medication administration process in schools more
      complex, not less.

PMID- 16563034
TI  - Implementing an over-the-counter medication administration policy in an
      elementary school.
AB  - A major focus of school nursing interventions is to improve school attendance. In
      many schools, parents are required to leave work and/or to arrange transportation
      to bring their children over-the-counter medicines. Many times these children
      went home, missing class and making it difficult to keep up with class work. The
      purpose of this study was to examine the impact of a new policy and procedure
      allowing school nurses to administer certain over-the-counter medications in
      elementary schools in a southern New Mexico public school district. "Sent home"
      rates before implementation of the new policy were compared with sent home rates
      for 2 years following implementation. Although not statistically significant,
      findings indicated that over-the-counter medication administration by school
      nurses does show a trend toward sending fewer students home and, therefore,
      keeping them in the learning environment.

PMID- 16563035
TI  - Development of a school nursing research agenda in Florida: a Delphi study.
AB  - Research is important to the image, visibility, and viability of school nursing.
      Each state school nursing association should evaluate member commitment to school
      nursing research based on their unique set of financial, educational, and
      organizational resources. A 3-round Delphi study was conducted in which Florida
      school nurses identified research priorities. The 10 priority research topics
      were (a) obesity/nutrition, (b) role of the school nurse, (c) legal/ethical
      issues, (d) emergencies, (e) health education, (f) absenteeism/attendance, (g)
      diabetes and insulin, (h) injuries, (i) health services, and (j) asthma. These
      topics form the state research agenda and will be used to guide the development
      of multisite school nursing studies.

PMID- 16563036
TI  - Teens' perceptions about attention deficit/hyperactivity disorder and
      medications.
AB  - This qualitative study describes teens' perceptions about attention
      deficit/hyperactivity disorder (AD/HD) and medications. The four modes of
      adaptation of the Roy Adaptation Model were the framework for this study. Data
      were collected through semistructured interviews with 15 high school teens aged
      14-17 with parent-reported AD/HD. An inductive analysis identified four themes:
      (1) physiologic (medication)--"Medications are a hassle, but they work"; (2) role
      function--"I do better in school when I take the meds"; (3) interdependence-"With
      meds things are better with my family, and friends don't know I am any
      different"; and (4) self-concept/group identity--"I'm just an everyday teenager,
      pretty much." The composite main theme was, "Meds help me." School nurses can use
      this information to guide interventions for families and teens with AD/HD and in
      working with health care providers, teachers, staff, and communities in a
      multidisciplinary effort toward an adaptive educational experience for teens.

PMID- 16563039
TI  - How can doctors help their patients to return to work?

PMID- 16563040
TI  - Assessing myocardial perfusion after myocardial infarction.

PMID- 16563041
TI  - What are the public health effects of direct-to-consumer drug advertising?
AB  - BACKGROUND TO THE DEBATE: Only two industrialized countries, the United States
      and New Zealand, allow direct-to-consumer advertising (DTCA) of prescription
      medicines, although New Zealand is planning a ban. The challenge for these
      governments is ensuring that DTCA is more beneficial than harmful. Proponents of
      DTCA argue that it helps to inform the public about available treatments and
      stimulates appropriate use of drugs for high-priority illnesses (such as statin
      use in people with ischemic heart disease). Critics argue that the information in
      the adverts is often biased and misleading, and that DTCA raises prescribing
      costs without net evidence of health benefits.

PMID- 16563042
TI  - Rational choices for allocating antiretrovirals in Africa: treatment equity,
      epidemiological efficiency, and feasibility.

PMID- 16563043
TI  - Drowning or thirsting: the extremes of availability of medical information.

PMID- 16563044
TI  - External quality assessment scheme in red blood cell serology: a 5-year
      experience in Thailand.
AB  - From 2000 to 2004, 36, 58, 72, 78, and 86 laboratories participated in an
      external quality assessment scheme (EQAS) organized by the Department of
      Transfusion Medicine, Faculty of Medicine Siriraj Hospital. Each year the staff
      was requested to perform ABO grouping, D typing, antibody screening, antibody
      identification, and DATs on eight blood samples. Each participant received
      information on the correct test results and a coded summary. Regarding ABO
      grouping, the error rate ranged from 0.3 to 1.3 percent, mostly due to human
      errors. Error rates in D typing ranged from 0.7 to 5.7 percent, the most
      problematic being weak D phenotype interpretation. Although every sample was
      negative by the DAT, error rates due to false positive test results were
      determined to be 0.4 to 2.1 percent. Antibody screening errors were also found;
      however, errors steadily decreased from 4.2 percent in 2000 to 0.3 percent in
      2004. Only 69.4 to 87.2 percent of laboratories performed antibody
      identification; however, correct results increased from 78.4 to 91.0 percent. In
      conclusion, an EQAS in RBC serology should be used to compare results from
      different laboratories and to identify those laboratories that need improvement
      in testing procedures.

PMID- 16563045
TI  - Human platelet alloantigen systems in three Chinese ethnic populations.
AB  - Knowledge of the prevalence of human platelet antigens (HPA) in different
      populations is important for effective diagnosis and management of immune
      mediated platelet disorders. The purpose of this study was to determine HPA gene
      frequencies in the majority Han ethnic population of China and in ethnic She and
      Tajik minority populations. Using PCR sequence specific primers, HPA- 1, -2, -3, 
      4, -5, and -6, we determined genotypes for ethnic Han, She, and Tajik blood
      donors. HPA gene frequencies for Chinese Han were found to be similar to those of
      She, reflecting the historic affinities of these two populations. HPA gene
      frequencies for Tajik were closer to those for Caucasians than to Chinese Han,
      She, or other Asian populations, reflecting their disparate origin and historic
      geographic isolation. HPA gene frequencies in these Chinese populations reflect
      their historic origins. Knowledge of these findings may be used to better
      understand and treat immune-mediated platelet disorders in these populations.

PMID- 16563047
TI  - H-deficient Bombay and para-Bombay red blood cells are most strongly agglutinated
      by the galactophilic lectins of Aplysia and Pseudomonas aeruginosa that detect I
      and P1 antigens.
AB  - The galactophilic lectins Aplysia gonad lectin (AGL) and Pseudomonas aeruginosa
      lectin (PA-IL), which detect human I and P1 RBC antigens, were examined for
      hemagglutination of H+ (group O and B) and H-deficient (Bombay and para-Bombay
      phenotype) RBCs. The results were compared with those obtained using two other
      galactophilic lectins, Maclura pomifera lectin (MPL) and Arachis hypogaea
      (peanut) agglutinin (PNA), which share T-antigen affinity, and two fucose-binding
      H-specific lectins, Ulex europaeus (UEA-I) and Pseudomonas aeruginosa lectin (PA
      IIL), as well as with those achieved with anti-I serum. The results revealed
      that, in contrast to UEA-I and PA-IIL, which preferentially agglutinated H+ RBCs,
      and to MPL and PNA, which similarly agglutinated all examined RBCs, AGL, PA-IL,
      and the anti-I serum agglutinated the H-deficient RBCs more strongly than did the
      H+ RBCs. These findings could be attributed to increased levels of I and P1
      antigens on those RBCs resulting from the use of the free common H-type 2
      precursor for their synthesis. Since both PA-IL and PA-IIL are regarded as
      potential pathogen adhesins, it would be interesting to statistically compare the
      sensitivities of individuals of H+ and H-deficient RBC populations to P.
      aeruginosa infections.

PMID- 16563046
TI  - Reduced red blood cell destruction by antibody fragments.
AB  - Antibodies to blood group antigens can cause immune RBC destruction directly
      (extravascular destruction) or indirectly through subsequent complement
      activation (intravascular hemolysis). The Fc portion of the IgG antibody is
      responsible for the effector functions of immune RBC destruction. We hypothesized
      that sensitization of RBCs with blood group antigen-specific IgG antibodies
      lacking their Fc portion would escape from the recipient's immune system,
      allowing for a longer survival period of the RBCs in the circulation. Direct
      injection of mouse RBC-specific Ter-119 monoclonal antibody into mice resulted in
      a more severe anemia compared with that in mice injected with the Ter-119 F(ab')2
      fragment. We found that mouse RBCs coated in vitro with the Ter-119 F(ab')2
      fragment, when transfused into mice, survived longer in circulation compared with
      RBCs coated with whole Ter-119 IgG molecule. The data support the conclusion that
      antibodies can be rendered less pathogenic through removal of their Fc portion.

PMID- 16563049
TI  - ISBT 128 blood labeling: introduction and reference laboratory applications.
AB  - ISBT 128 will be implemented in the United States during the next two years. In
      addition to improving unit traceability and lookback tracking, this information
      technology standard has the power to detect and prevent errors in data entry by
      using data identifiers and check characters. Additionally, its ability to encode
      special testing results such as CMV and RBC phenotype on a label provides
      laboratories a computerized mechanism to verify the accuracy of such labels.

PMID- 16563048
TI  - A single base insertion of the 4-alpha-galactosyltransferase gene led to the
      deficiency of Gb3 biosynthesis.
AB  - cDNAs for alpha 1,4 galactosyltransferase (A4GALT) have been isolated. To explore
      the molecular basis of the p phenotype in Japanese donors, we analyzed the A4GALT
      gene sequences of normal and p phenotype samples. The coding region in the A4GALT
      gene for DNA sequencing was amplified by PCR amplification. A4GALT expression
      vectors for individual were constructed by PCR amplification of the coding region
      using primers and subsequent subcloning into an expression vector. The expression
      of Gb3/CD77 antigen on the cell surface was evaluated by flow cytometry and by
      immunochemical techniques. All individuals with the p phenotype were found to
      have a single base insertion (A4GALT/insC) at the same nucleotide position.
      Neither the transfectant cells with a mutant gene (A4GALT/insC) of donor origin
      or those with a synthesized mutant gene (A4GALT/insC-Mu) expressed Gb3 antigen
      indicating that the presence of A4GALT/insC diminished the A4GALT enzyme
      activity. In addition, an allele-specific PCR (ASP) system was developed in which
      of the p phenotype with A4GALT/insC can be unambiguously discriminated from
      normal donors. Based on the finding that a single base insertion (A4GALT/insC)
      diminishes A4GALT activity, an ASP assay was developed to detect individuals with
      this particular p phenotype.

PMID- 16563050
TI  - Suicide in farmers in Scotland.
AB  - INTRODUCTION: Farmers and farm workers have higher than expected rates of suicide
      and undetermined deaths in UK studies, and some rural areas of Scotland have
      higher than average male suicide rates. Firearm access seems to be an influencing
      factor in England and Wales. Type of farming, and farming social networks may
      also be important. This article describes suicide and undetermined deaths in male
      farmers and farm workers in Scotland from 1981-1999 using anonymised, routine
      data. METHOD: Deaths of men aged 15-74 years from suicide or undetermined cause
      were identified from anonymised Scottish death records. Farmers and farm workers
      were identified using occupation codes. Methods of suicide used by farmers were
      compared with those of the general male population of the same age. A multiple
      linear regression was used to examine the influence of farm type, and the
      proportion of farmers in the working population of an area. RESULTS: 307 male
      farmers or farm workers died by suicide or undetermined cause in the time period.
      The overall rate was 31.4/100,000 per year (95% CI 28.1-35.1). Deaths using
      firearms were over-represented (29% of farming deaths compared with 3.6% in the
      general male population). There was no significant association between the male
      suicide rate in an area, and the farming suicide rate. Areas with lower
      proportions of farmers tended to have higher rates of farming suicide and
      undetermined deaths. This one factor described 85% of the variance among areas.
      CONCLUSION: Deaths were substantially more likely to involve firearms than
      suicide and undetermined deaths in the general male population. Less use of other
      methods did not completely compensate for this, indicating that method
      availability is likely to contribute to farming suicide rates. Farmers in areas
      where farming is less common were more likely to die by suicide, and this
      described most of the differences among areas. Networks and social supports may
      be important protective factors for farmers.

PMID- 16563052
TI  - Potentially inappropriate prescribing for geriatric inpatients: an acute care of
      the elderly unit compared to a general medicine service.
AB  - OBJECTIVE: To compare potentially inappropriate medication prescribing, as
      defined by the updated Beers criteria, in an acute care of the elderly (ACE) unit
      and a general medicine service. DESIGN: Non-concurrent cohort study of admitting
      and discharge summaries from an electronic medical record system. SETTING: A
      general medicine service and ACE unit at an 880-bed, tertiary care, teaching
      hospital. PARTICIPANTS: 176 patients from the ACE unit and 173 from the general
      medicine service who were 65 years of age or older, admitted after October 1,
      1999, and discharged before February 29, 2000. MAIN OUTCOME MEASURE(S): Numbers
      of high- and low-severity potentially inappropriate medications (PIMs) and total
      medications on admission and discharge. RESULTS: The average number of all
      medications added on discharge was lower for the ACE unit versus general medicine
      service, 0.13 versus 0.75, respectively (P = .027). In the ACE unit, 11% of
      patients were prescribed PIMs with high-severity outcomes on discharge, either
      independent or dependent of diagnosis, compared with 12.7% in the general
      medicine service. The mean change in potentially inappropriate diagnoses
      independent medications upon discharge was - 0.09 in the ACE unit versus + 0.09
      in the general medicine service (P = .011). CONCLUSION: Although detected
      differences were small, PIMs were less likely to be prescribed and more likely to
      be discontinued in the ACE unit. No differences were found in the majority of
      comparisons between groups.

PMID- 16563051
TI  - Establishment of and first 20 months of operating an outreach geriatric clinic in
      a regional centre.
AB  - INTRODUCTION: Providing geriatric assessments to older people residing in rural
      or remote areas is a challenge due to the complexities of distance and a
      declining medical workforce. This study aimed to develop a feasible model of
      service delivery in a rural area, delivering specialised falls and memory clinics
      similar to those available in the metropolitan area. At the end of the first 20
      months we evaluated the service in terms of patient access and the satisfaction
      of the local health care providers. METHODS: A meeting was held with key
      stakeholders to identify existing service provision in the region, and to
      determine which services were needed. Clinic attendance and information on
      services provided by the clinic were collected. Questionnaires regarding clinic
      performance were sent to health-care providers in the region. RESULTS: The
      stakeholder meeting identified communication, collaboration and continuing
      education as the main services required of the clinic. The clinic model included
      a specialist geriatrician and an extended practice nurse specialising in aged
      care. Between May 2003 and Dec 2004, 115 people were assessed by the extended
      practice nurse. Interventions relating to falls and cognition were accessed by
      clients. Time from referral to seeing a specialist and failure to attend rates
      were comparable to rates seen in the metropolitan clinics. All heath-care
      providers who responded to the survey found the service useful. CONCLUSION: Our
      clinic model is a possible mechanism for delivering ambulatory aged care services
      to rural and remote regions. This model of care did not improve access or shorten
      waiting times for attendees. Future models of specialised rural care need to
      explore innovative workforce strategies to improve access.

PMID- 16563053
TI  - A renaissance for fluoxetine in the management of depression in the elderly?
AB  - OBJECTIVE: To review the literature pertaining to the use of the selective
      serotonin reuptake inhibitor (SSRI) fluoxetine in the management of depression in
      elders. DATA SOURCES: A MEDLINE search was conducted to identify pertinent
      studies, case reports, letters, and reviews in the English language. All articles
      published from 1986 to 2002 were reviewed. Additional references were obtained
      from bibliographies of those articles. STUDY SELECTION: All studies evaluating
      any aspect of the use of fluoxetine in managing geriatric depression. DATA
      SYNTHESIS: Pharmacokinetic studies have demonstrated that the potential for
      accumulation of fluoxetine and its active metabolite norfluoxetine with chronic
      dosing in elders is less than or equal to that in young individuals. Renal
      impairment, a frequent comorbidity of older age, has no significant effect on the
      pharmacokinetics of fluoxetine/norfluoxetine. In elders, the efficacy of
      fluoxetine is statistically indistinguishable from that of paroxetine,
      sertraline, fluvoxamine, and tricyclic antidepressants in controlled trials, as
      are the adverse event profiles of fluoxetine and other tested SSRIs. The drug
      interaction potential of fluoxetine is similar to that of fluvoxamine and
      paroxetine and greater than those of citalopram, escitalopram, and sertraline.
      CONCLUSION: Available data support a reevaluation of the role of fluoxetine in
      the management of geriatric depression, especially in light of the recent
      marketing of a generic fluoxetine product that is priced much lower than
      competitor branded SSRIs. Further studies of fluoxetine use in geriatric
      depression using adequate numbers of patients are recommended.

PMID- 16563054
TI  - Forging local pharmaceutical partnerships.

PMID- 16563055
TI  - Pharmacotherapy of behavioral and psychological symptoms of dementia: a review of
      atypical antipsychotics.
AB  - OBJECTIVE: To review the literature on use of antipsychotics to treat behavioral
      and psychological symptoms of dementia (BPSD). DATA SOURCES: Information was
      selected from a MEDLINE search of English-language medical literature using the
      search terms "antipsychotics" and "elderly." Manual searches of pertinent journal
      article references, and review of poster presentations at recent professional
      meetings were also performed. STUDY SELECTION: Meta-analyses published in 1990
      and 1998 were used as a starting point for information about conventional
      antipsychotics. Articles reporting the results of controlled trials of
      conventional antipsychotics published since the second meta-analysis (October
      1998) were included. Also included were articles reporting the results of
      controlled clinical trials of atypical antipsychotics (i.e., clozapine,
      risperidone, olanzapine, quetiapine, ziprasidone) for the treatment of dementia
      in the elderly. Studies and post hoc analyses of special patient populations
      (Parkinson's disease, schizophrenia, treatment-refractory BPSD) were excluded.
      One open-label extension and one post hoc analysis were included because they
      provide valuable information about the long-term use of atypical antipsychotics.
      One poster was included, as it contained the only data available from a
      controlled trial of quetiapine. DATA EXTRACTION: Data were extracted from the
      literature, as well as a recent scientific poster presentation. Two meta-analyses
      and six controlled studies were identified for inclusion. DATA SYNTHESIS: There
      are few controlled clinical trials of the use of antipsychotics in elderly
      patients with dementia. Currently available information indicates these
      medications are useful in the treatment of behavioral and psychological symptoms
      of dementia, but the clinician must exercise caution because of the drugs'
      potential side effects. CONCLUSION: While widely prescribed on an "off-label"
      basis, there is a dearth of placebo-controlled clinical trials necessary to
      evaluate safety, and head-to-head comparative studies necessary to contrast
      efficacy and safety of atypical antipsychotics in treating BPSD.

PMID- 16563056
TI  - Update on gabapentin therapy of neuropathic pain.
AB  - OBJECTIVE: To provide current information regarding the efficacy and tolerability
      of the anticonvulsant gabapentin in the management of neuropathic pain. DATA
      SOURCES: A MEDLINE search was conducted to identify pertinent studies, case
      reports, letters, and reviews in the English language published from 1986 through
      October 2002. Additional references were obtained from the bibliographies of
      these articles. STUDY SELECTION: All studies evaluating any aspect of use of
      gabapentin as an analgesic. DATA SYNTHESIS: Numerous case reports and series
      (total N = 750) have suggested efficacy of gabapentin in daily doses of up to 3.6
      g. Controlled trials in painful diabetic neuropathy, postherpetic neuralgia, and
      multiple sclerosis have confirmed the potential utility of this agent in a
      variety of neuropathic pain syndromes (total N = 511). Central nervous system
      side effects are of most concern with gabapentin. The absence of significant drug
      drug interactions makes this agent a preferred treatment choice, as opposed to
      anticonvulsants such as carbamazepine or lamotrigine. CONCLUSION: In human pain
      models using patients with neuropathic pain, gabapentin has been found effective
      against both spontaneous and evoked pain, and these effects are independent of
      the pain source. Gabapentin, in doses ranging up to 3.6 g/day, has demonstrated
      efficacy in a variety of neuropathic pain states, including those refractory to
      agents such as the tricyclic antidepressants (TCA) and other anticonvulsants. A
      major question today is whether gabapentin should be considered as first-line
      therapy (i.e., even before a trial of a TCA or carbamazepine) or as second-line
      therapy for individuals unresponsive to or intolerant of TCAs and/or
      carbamazepine.

PMID- 16563058
TI  - Strategies for prevention of medication-related falls in the elderly.
AB  - OBJECTIVE: To review the literature pertaining to the relationship between
      medications and fall risk in the elderly, and the role of the pharmacist in
      preventing falls. DATA SOURCES: A MEDLINE search was conducted to identify
      relevant studies, review articles, case reports, and letters in the English
      language published from 1985 to June 2002. Additional references were obtained
      from bibliographies of those articles. STUDY SELECTION: All studies evaluating
      the relationship between medications and falls, or the role of the pharmacist in
      preventing falls, that were accessible to the authors. DATA SYNTHESIS:
      Pharmacists have tremendous opportunities caring for patients who are considered
      to be at risk for a fall. Numerous drugs have been suspected of contributing to
      the risk of a fall. With proper identification of risk factors, the pharmacist
      can appropriately select medications while monitoring their efficacy and adverse
      effects, assist in early detection and treatment of common medical problems that
      contribute to falls, perform environmental-hazard assessments, provide patient
      and caregiver education, and suggest physical therapy and gait and balance
      training. Once a fall has occurred, the pharmacist can reduce the risk of a
      subsequent fall by reviewing medications and other risk factors, recommending
      drug therapy changes, and educating other health care professionals and
      caregivers. Interventions by pharmacists have been shown to reduce the rate of
      falls significantly. CONCLUSIONS AND CLINICAL APPLICATIONS: Pharmacists have many
      opportunities to reduce the risk of a fall. The assessment of each patient for
      risk factors should guide therapeutic choices for underlying diseases. Prevention
      of falls should be accomplished by reducing environmental risks, properly
      identifying and managing age-related changes in the individual, utilizing
      appropriate medications when warranted, and discontinuing medications that are
      not needed. Pharmacists can also provide valuable expertise in educating other
      health care professionals regarding fall risks and the appropriate usage of
      medications.

PMID- 16563057
TI  - Physician acceptance rate of pharmacist recommendations to reduce use of
      potentially inappropriate medications in the assisted living setting.
AB  - OBJECTIVE: To reduce the number of potentially inappropriate medication orders,
      based on the Beers' criteria, for an elderly population residing in assisted
      living facilities through consultant pharmacist medication review, interventions,
      and recommendations DESIGN: Prospective case series of consultant pharmacist
      recommendations. PATIENTS: Census of 456 residents of assisted living facilities
      who received a new or refill medication order during the preceding two months.
      INTERVENTIONS: Potentially inappropriate medications for the elderly were
      identified and recommendation letters faxed to the physician for consideration.
      MAIN OUTCOME MEASURES: Demographic characteristics, prevalence data for
      medications ordered and considered potentially inappropriate based on the Beers'
      criteria, and physician acceptance and return rate of recommendations. RESULTS:
      The data demonstrated that 31.6% of the residents in this study were receiving
      one or more routine or p.r.n. medications orders considered potentially
      inappropriate based on the Beers' criteria. The majority (82.9%) of the residents
      were female, and the average age of the residents was 85.4 +/- 7.34 SD years
      (range, 66-102 years). A total of 205 routine and p.r.n. medication orders were
      identified as potentially inappropriate. Of these orders, 16.7% were discontinued
      and 2.5% were changed to lower dosage regimens. The overall return rate of all
      recommendations faxed to physicians was 88.7%. CONCLUSIONS: Potentially
      inappropriate medications, according to the Beers' criteria for use in the
      elderly, are ordered at a high rate for residents of assisted living facilities.
      Though not mandated in all states, screening of these orders by a consultant
      pharmacist, with recommendations for alternative pharmacotherapy of less risk,
      would be appropriate. Physicians do address the recommendations in the majority
      of cases, but the physician acceptance rate of those recommendations is much
      lower. Consultant pharmacists have the opportunity to educate physicians of the
      risks of using medications considered potentially inappropriate for geriatric
      patients. Further studies are needed to determine barriers to physician
      acceptance of these recommendations.

PMID- 16563059
TI  - NIH research and funding priorities for 2003.

PMID- 16563060
TI  - Use of the cognitive performance scale to identify under- and over-treatment of
      cognitive deficits in nursing home residents with dementia.
AB  - OBJECTIVE: To determine the practicality of using the Minimum Data Set (MDS)
      Cognitive Performance Scale (CPS) to evaluate the appropriateness of
      acetylcholinesterase inhibitor (AChEI) use in the treatment of Alzheimer's
      disease and related disorders. DESIGN: A cross-sectional study of nursing
      facility residents using the medical record and MDS data. SETTING: Three skilled
      nursing facilities. PATIENTS/PARTICIPANTS: 275 residents with MDS assessments
      completed from March 1 through September 30, 2000. INTERVENTIONS: None. MAIN
      OUTCOME MEASURE(S): CPS scores and documented diagnoses for those residents who
      received and did not receive AChEI therapy. RESULTS: The median CPS score for all
      subjects was 3 (range, 0-6), with significant differences (P = .000; chi square)
      among the facilities. Overall, 13.8% of subjects received an AChEI, most commonly
      donepezil. As only 12.9% of residents with mild to moderate impairment were
      receiving an AChEI, they may have been under-treated. However, over-treatment may
      have been an issue among the 16.2% of subjects with severe impairment who were
      treated. Differences among facilities could have reflected differences in patient
      populations or procedures used to complete the MDS. CONCLUSION: The CPS is a
      practical tool for nursing facilities to use to standardize the assessment of
      cognitive function. The CPS could be used by pharmacists and others as an adjunct
      to the assessment of the effectiveness of interventions, such as AChEI therapy,
      to improve or maintain the functional status of nursing facility residents.
      Further studies are necessary before the CPS could be used, by itself, to direct
      pharmacotherapy of cognitive impairment.

PMID- 16563061
TI  - Newer insulin therapies for management of type 1 and type 2 diabetes mellitus.
AB  - OBJECTIVE: To provide an overview of type 1 and type 2 diabetes mellitus and
      review newer insulin therapies used to manage patients with diabetes. DATA
      SOURCES: A MEDLINE search covering articles published from 1985 to March 2003 was
      conducted to identify English-language literature available on the management of
      diabetes, specifically focusing on the newer insulin products insulin glargine
      and insulin aspart, and any other novel insulin therapies (Medical Subject
      Headings [MeSH] search terms used were: diabetes, insulin, insulin aspart,
      insulin glargine, inhaled insulin, intranasal insulin, oral insulin). These
      articles, abstracts, and data provided by the pharmaceutical manufacturers were
      reviewed to collect pertinent data. Additional references were obtained from the
      bibliographies of those publications. STUDY SELECTION: Human studies presenting
      safety or efficacy information on newer insulin formulations. DATA EXTRACTION:
      Specific insulin formulations were reviewed with regard to background
      information, pharmacokinetic data, relevant clinical studies, U.S. Food and Drug
      Administration-approved indications, dosing and administration, adverse effects,
      storage, cost, and role in therapy. DATA SYNTHESIS: Insulin therapy is essential
      in the management of patients with type 1 diabetes, as well as in many patients
      with type 2 diabetes. No single insulin product currently on the U.S. market
      mimics natural endogenous insulin secretion. Problems encountered with
      traditional insulin products include variable absorption, peaks leading to
      hypoglycemic events, troughs leading to inadequate duration of response, and
      difficulty accurately timing injections in relation to meals. Insulin analogs
      such as insulin glargine and insulin aspart have been synthesized in an effort to
      overcome those difficulties. Novel insulin formulations (oral, intranasal, and
      inhaled) are also in various stages of investigation. CONCLUSION: Insulin
      glargine and insulin aspart are two of the newest insulin products approved for
      managing diabetes mellitus. Clinical trials have shown that these agents may
      offer certain clinical benefits and conveniences for patients. These advantages,
      however, must be weighed against the increased cost of insulin glargine and
      insulin aspart relative to traditional insulins.

PMID- 16563062
TI  - Grapefruit juice and potential drug interactions.
AB  - OBJECTIVE: To review current literature pertaining to the potential interaction
      of several classes of drugs with grapefruit juice, and to discuss the mechanism
      and causative agents in such interactions. DATA SOURCES: A MEDLINE search
      covering the period 1989-2002 was performed to identify review articles, studies,
      and case reports referencing the potential interaction of grapefruit juice with
      several classes of drugs. The bibliographies of the selected articles were
      reviewed for additional references. STUDY SELECTION: Human studies and case
      reports describing the mechanism and potential interaction of grapefruit juice
      and several classes of drugs. DATA EXTRACTION: Studies were reviewed for design
      characteristics, as well as data relevant to the severity of a drug or drug
      class' interaction with grapefruit juice. Data were also extracted relevant to
      the possible causative agents of an interaction with grapefruit juice. DATA
      SYNTHESIS: Grapefruit juice acts by blocking the activity of cytochrome P-450
      (CYP) 3A4 isoenzyme in the intestinal wall, thereby preventing the presystemic
      first-pass metabolism of a wide range of drugs. Studies and case reports continue
      to analyze the specific active components of grapefruit juice and the medications
      with which it interacts. CONCLUSION: Researchers continue to work to determine
      the constituents of grapefruit juice responsible for CYP enzyme inhibition and P
      glycoprotein activation in clinical settings. Some trials have pointed
      researchers in the direction of compounds such as naringin, naringenin, and 6,7
      dihydroxybergamottin as possible active agents. Calcium channel antagonists,
      neuropsychiatric medications, statins, and antihistamines are just a few of the
      drug classes whose actions are significantly affected by the consumption of
      grapefruit juice. Patients and other health care professionals need to be
      educated about potential drug interactions with grapefruit juice.

PMID- 16563063
TI  - Advances in pharmacotherapy of psychotic disorders in the elderly.
AB  - OBJECTIVE: To evaluate the literature on the pharmacotherapy of psychosis in the
      elderly. DATA SOURCES: Searches of MEDLINE (1996-April 2002) and the Cochrane
      Database using the terms psychosis, elderly, geriatric, dementia, Alzheimer's
      disease, Parkinson's disease, antipsychotics, atypical antipsychotics, clozapine,
      risperidone, olanzapine, quetiapine, ziprasidone, and haloperidol were performed.
      An updated search of psychosis, risperidone, olanzapine, quetiapine, ziprasidone,
      and aripiprazole occurred in April 2003. STUDY SELECTION: Reviews, case reports,
      and open-labeled and controlled trials were selected. DATA SYNTHESIS: Psychotic
      symptoms in the elderly can occur in the context of psychiatric disorders,
      medical conditions, or as a medication complication. Behavioral problems (e.g.,
      agitation, aggression) can accompany psychosis and may not respond to
      nonpharmacological strategies. Pharmacological management of psychosis in the
      elderly with typical antipsychotics (e.g., haloperidol, chlorpromazine) can
      result in intolerable adverse effects (e.g., sedation, anticholinergic effects,
      extrapyramidal symptoms, tardive dyskinesia, and orthostatic hypotension). The
      atypical antipsychotic agents (e.g., risperidone, olanzapine, quetiapine,
      ziprasidone) and the dopamine-serotonin system stabilizer aripiprazole offer more
      tolerable adverse effects profiles. Most information supporting the use of the
      atypical antipsychotics is derived from open-label trials involving patients with
      dementia or Parkinson's disease; however, data from large randomized, controlled
      trials is emerging. In general, psychosis in elderly patients responds to low
      doses of antipsychotics. Patients must be monitored closely for adverse effects,
      especially in light of the new information associating cerebrovascular adverse
      events with risperidone in patients with dementia. Further trials are required to
      determine if this is a disease- or drug-specific phenomenon. CONCLUSION:
      Psychosis in elderly patients can be managed with antipsychotic agents. The
      atypical antipsychotics are effective and offer advantages over typical
      antipsychotics with regard to a reduced rate of adverse effects.

PMID- 16563064
TI  - Drug forecast: memantine, prototype of a new approach to treatment of dementia.
AB  - OBJECTIVE: To review the first clinically useful N-methyl-D-aspartate (NMDA)
      inhibitor for the treatment of dementia, memantine. DATA SOURCE: A MEDLINE/PUBMED
      search was conducted to identify pertinent studies, case reports, letters, and
      reviews in the English language. All articles published from 1950 to March 2003
      were reviewed. Additional references were obtained from the bibliographies of
      these articles. STUDY SELECTION: All studies evaluating any aspect of memantine
      in humans. DATA SYNTHESIS: The excitatory amino acid neurotransmitter glutamate
      is felt to play a role in neuroinflammation and destruction of cholinergic
      neurons associated with dementia. Memantine is an NMDA receptor antagonist which
      partially blocks glutamatergic neurotransmission in the central nervous system
      (CNS). It is a selective, moderate affinity, noncompetitive receptor blocker that
      rapidly associates with and dissociates from the NMDA receptor. Memantine, that
      is usually dosed once or twice daily, is predominantly eliminated as unchanged
      drug via the renal route (renal clearance accounts for 90% of total body
      clearance). Use of memantine is associated with significant improvements in a
      number of cognitive, functional, and behavioral assessment scales used in the
      evaluation of cognition-enhancing drugs in dementia. Adverse effects of memantine
      are generally referable to the CNS and include depression, insomnia, akathisia,
      agitation, dizziness, drowsiness, restlessness, and hyperexcitability.
      CONCLUSION: Although there is no cure for dementia, memantine may delay disease
      progression and improve functioning to a clinically significant extent. However,
      efficacy has not been consistent within trials and no comparative data with
      acetylcholinesterase inhibitors (AchEI) are available. In addition, there are no
      controlled data available regarding combination memantine-AchEI therapy. Further
      study data are awaited.

PMID- 16563065
TI  - Retrospective survey of long-term care staff: 12 conditions identified,
      evaluated, and reported as suspected adverse drug reactions.
AB  - OBJECTIVE: To examine the identification of conditions, the evaluation of these
      conditions as adverse drug reactions (ADRs), and the communication practices
      regarding suspected ADRs in a long-term care (LTC) facility. DESIGN AND SETTING:
      Health care providers completed a survey containing nine questions covering 13
      conditions, about residents of a 99-bed LTC facility. PARTICIPANTS: Twenty-five
      health care providers (i.e., CNAs, LPNs, RNs, RPh, social workers, and an
      activities worker) reviewed residents on their units. A total of 67 residents
      were reviewed. RESULTS: The RPh was aware of fewer of the residents' conditions
      (16% of all conditions) compared with CNAs (34%), LPNs (38%), and RNs (45%). RNs
      and the RPh identified an equal percent of conditions that could be caused by a
      resident's medications (66.5% and 66.7% of all conditions, respectively). This
      was greater than LPNs (36%) or CNAs (9.9%). However, RNs and the RPh actually
      attributed a lower percentage of these conditions to the medications (43.9% and
      41.7%, respectively) compared with LPNs (57.4%) and CNAs (90.0%). CNAs notified
      others in a higher percentage of the cases where they suspected an ADR (81.5%)
      compared with the RPh (60%), RNs (57.4%), or LPNs (10.3%). No notification was
      primarily attributed to "nothing could be done," the condition is an expected
      effect, others were aware of the condition, and the condition currently is being
      treated. CONCLUSIONS: These results illustrate the importance of a team approach
      to ensure that all health care providers are aware of conditions to properly
      evaluate and resolve them.

PMID- 16563066
TI  - Megestrol acetate therapy in geriatric patients: case reviews and associated deep
      vein thrombosis.
AB  - OBJECTIVE: To provide a brief review of the literature discussing treatment of
      unplanned weight loss in geriatric patients, focusing on megestrol acetate and to
      report two cases of deep vein thrombosis (DVT) associated with megestrol acetate
      therapy in geriatric nursing facility residents. DATA SOURCES: Biomedical
      literature accessed through MEDLINE and PubMed (1990-2003); product manufacturer
      information. DISCUSSION: Unplanned weight loss, a common problem among frail
      geriatric nursing facility residents, is associated with increased morbidity and
      mortality. Once reversible causes of weight loss are identified and addressed,
      dietary changes, including the addition of nutritional supplements, may be of
      benefit. In some cases, medications are prescribed. Megestrol acetate oral
      suspension is approved by the Food and Drug Administration for the treatment of
      anorexia, cachexia, or unexplained significant weight loss in patients with AIDS.
      Megestrol acetate tablets are FDA-approved for palliative treatment of advanced
      breast or endometrial cancer. In recent years, several published prospective and
      retrospective reports have described the use of megestrol acetate for unplanned
      weight loss in geriatric patients. While clinical efficacy trials reported
      diarrhea, impotence, and rash as the most commonly occurring adverse events, post
      marketing reports have included deep vein thrombosis and pulmonary embolism. DVP
      has occurred in geriatric patients. CASE SUMMARIES: Case #1: An 86-year-old
      female with Alzheimer's disease and decreased oral intake was prescribed
      megestrol acetate suspension 400 mg po bid after a 30-day weight loss of 4.8 kg.
      Ten days later she developed DVT. Megestrol acetate was discontinued, and she was
      hospitalized and treated, recovering successfully. Case #2: An 85-year old female
      with Alzheimer's disease who had stopped eating was prescribed megestrol acetate
      tablets 40 mg po bid. Four months later she developed DVT. Megestrol acetate was
      discontinued and she was hospitalized and treated, recovering successfully.
      CONCLUSION: Thromboembolic events are potential adverse events associated with
      megestrol acetate therapy. Caution should be observed in using megestrol acetate
      in geriatric patients, especially nursing facility residents who often have
      impaired mobility.

PMID- 16563067
TI  - Divalproex sodium use in the elderly: a new formulation offers new opportunities.

PMID- 16563068
TI  - Women's perception of bone-mineral density testing and osteoporosis education in
      the community pharmacy.
AB  - OBJECTIVE: The objective of this study was to assess women's level of acceptance
      and attitudes toward bone-mineral density (BMD) testing and osteoporosis
      education in the community pharmacy. DESIGN: The study design was a questionnaire
      with 13 statements using a five-point scale anchored from "strongly disagree" to
      "strongly agree." The statements focused on the value and comfort level of BMD
      testing in a pharmacy, confidence in pharmacists, osteoporosis education in the
      pharmacy, and payment for such services. One-sample t-tests were used to assess
      whether the responses statistically differed from the midpoint scale value.
      Comparisons also were made between demographic characteristics (education level,
      family history of osteoporosis, and daily calcium intake). SETTING: An
      independently owned grocery store chain (Bashas') in the Phoenix, and Tucson,
      Arizona, metropolitan areas. PATIENTS: The survey was administered to women upon
      completion of a BMD screening. MAIN OUTCOME MEASURES: Responses to 13 statements
      and demographic questions. RESULTS: Eighty women completed the survey. Women
      strongly agreed that BMD testing in community pharmacies was valuable and that it
      would increase the public's awareness of osteoporosis. For all 13 statements,
      respondents strongly agreed or agreed with the importance and role of BMD
      testing. All responses were statistically significantly greater than the midpoint
      scale value (P<0.001). There were no statistically significant differences in
      responses among women with higher education, with a family history of
      osteoporosis, and who take daily calcium (P>0.05). CONCLUSIONS: These women's
      opinions suggest that BMD testing has a useful role in community pharmacies.

PMID- 16563069
TI  - Lamotrigine: treatment of epilepsy in the elderly.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical use, and
      potential adverse effects of lamotrigine in elderly patients with epilepsy. DATA
      SOURCES: English-language literature regarding humans was searched from January
      1990 through January 2003 using PubMed and the terms "lamotrigine," "epilepsy,"
      and "elderly." STUDY SELECTION: Studies of epilepsy treatment with lamotrigine in
      elderly patients, review articles, pharmacokinetic and pharmacodynamic studies,
      and clinical studies/reports regarding adverse effects of lamotrigine were
      evaluated. Two studies specifically dealing with lamotrigine treatment of
      epilepsy in the elderly were reviewed in detail. DATA EXTRACTION: Data from
      identified publications were included. Relevant data from other patient
      populations were evaluated and used to develop recommendations. DATA SYNTHESIS:
      The pharmacokinetic and pharmacologic profiles of lamotrigine were evaluated to
      assess this drug's utility for treatment of epilepsy in the elderly. Safety,
      efficacy, and frequency of common side effects such as sedation and cognitive
      interference were assessed and compared with those of other antiepileptic drugs.
      Risk factors for less common, serious adverse effects such as skin rash and
      hypersensitivity were evaluated. Specific risks to elderly patients related to
      these adverse effects were assessed. Potential interactions between lamotrigine
      and other drugs likely to be used in elderly patients with seizure disorders were
      evaluated. CONCLUSION: Lamotrigine is an effective antiepileptic drug in the
      elderly. It has a favorable side effect profile when accepted dosage
      recommendations are followed. Elderly patients do not appear to be at increased
      risk for lamotrigine-induced skin rashes and hypersensitivity reactions.
      Cotherapy with valproate may increase the likelihood of skin rash. Combined
      treatment with lamotrigine and carbamazepine may increase central nervous system
      (CNS) adverse effects. Interactions between lamotrigine and other drugs are
      uncommon. Additional evaluations of long-term outcomes in elderly patients
      treated for epilepsy with lamotrigine will clarify the place of this drug in
      therapy.

PMID- 16563070
TI  - The use of medications with known or potential anticholinergic activity in
      patients with dementia receiving cholinesterase inhibitors.
AB  - OBJECTIVES: To assess the prevalence of prescribed medications with
      anticholinergic activity given concurrently with acetylcholinesterase-inhibitor
      therapy in long-term care residents with dementia and to recommend dose
      adjustment or discontinuation of these medications with anticholinergic activity.
      DESIGN: Prospective case series. SETTING: Long-term care facilities in Indiana.
      PATIENTS: Geriatric residents in long-term care facilities were included if they
      were receiving both an agent with anticholinergic activity as determined by
      radioreceptor assay and an acetylcholinesterase inhibitor. INTERVENTIONS:
      Recommendations were made to the resident's physician suggesting substitution,
      dose reduction, or discontinuation of the agent with anticholinergic activity.
      MAIN OUTCOME MEASURES: The number of residents with a recommended change in their
      anticholinergic medication regimen as a result of the consultant pharmacist's
      recommendation. RESULTS: Of the 2,021 long-term care residents evaluated, 498
      (25%) were receiving an acetylcholinesterase inhibitor. Of the 498 residents
      receiving acetylcholinesterase inhibitor therapy, 103 (20.7%) were receiving
      concurrent medications with anticholinergic activity. The most commonly
      prescribed medication with anticholinergic activity was furosemide, an agent with
      "possible" or low anticholinergic effects. One hundred forty-six medications with
      anticholinergic activity were used in these 103 residents. Overall, adjustments
      to the agents with anticholinergic activity were completed in 24 (16.4%) cases.
      The majority of medications prescribed had "possible" anticholinergic activity
      (62.3%) compared with those prescribed with "definite" anticholinergic activity
      (37.7%). No medication dose adjustments or discontinuations were frequent,
      regardless of whether the medication was deemed to have "definite" (29.1%) or
      "possible" (31.9%) anticholinergic activity. Medication changes or
      discontinuations occurred in 13 (23.6%) agents with "definite" and 11 (12.1%)
      agents with "possible" anticholinergic activity. CONCLUSIONS: Medications with
      anticholinergic activity may interfere with the beneficial effects of
      acetylcholinesterase inhibitors. Attention should be placed, however, on agents
      with moderate or strong anticholinergic activity or the use of multiple
      medications with anticholinergic activity. Health care providers should consider
      the risk versus benefit of using agents with anticholinergic activity in someone
      with cognitive impairment receiving an acetylcholinesterase inhibitor.

PMID- 16563072
TI  - The central nervous system and peripheral impact of using anticonvulsant
      medications: a focus on phenytoin and its monitoring parameters.

PMID- 16563071
TI  - Diagnosis, treatment, and prevention of Clostridium difficile colitis.
AB  - OBJECTIVE: To review the risk factors for, diagnosis and treatment of, and
      strategies for prevention of, Clostridium difficile colitis. The pharmacists'
      role in optimizing drug therapy is discussed. DATA SOURCES: A Medline search was
      conducted to identify pertinent clinical studies, consensus guidelines, case
      reports, and clinical reviews published in the English language through 2002.
      STUDY SELECTION: Chosen studies evaluated the appropriate clinical management and
      prevention of Clostridium difficile colitis. Studies selected focused on
      pharmacists' role in the institutional management of this disease. DATA
      SYNTHESIS: Major risk factors for developing Clostridium difficile colitis
      include renal failure, prolonged hospitalization, age greater than 60, and
      prolonged exposure to antibiotics. Outpatients are colonized with Clostridium
      difficile at a rate of about 3 percent while hospitalized patients may have a ten
      fold higher colonization rate. Clinical presentation of C. difficile colitis
      includes diarrhea, abdominal cramps, fever, nausea, malaise, anorexia, and
      dehydration. Treatment consists primarily of oral or parenteral metronidazole for
      10 to 14 days. Mandatory infection control and educational programs for both
      nursing and environmental services staff can greatly reduce the number of
      institutional infections. Pharmacists can play a key role in these programs as
      well as optimizing drug therapy. CONCLUSION: C. difficile colitis is a hospital
      acquired infection that occurs primarily in elderly debilitated patients
      following the prolonged use of certain antibiotics. Its incidence can be reduced
      through aggressive infection control procedures and staff education.

PMID- 16563074
TI  - The clinical implications of DSM-IV personality disorder comorbidity in depressed
      inpatients: a replication study in an Italian setting.

PMID- 16563075
TI  - Reported childhood onset of self-mutilation among borderline patients.
AB  - The purpose of this study was to determine the percentage of borderline patients
      who first engaged in self-mutilation as children and to compare the parameters of
      their self-harm to those of borderline patients who first harmed themselves at an
      older age. Two hundred and ninety inpatients meeting both Revised Diagnostic
      Interview for Borderlines (DIB-R; Zanarini, Gunderson, Frankenburg, & Chauncey,
      1989) and Diagnostic and Statistical Manual of Mental Disorders (3rd ed. ref.)
      (DSM-III-R; APA, 1987) criteria for borderline personality disorder were
      interviewed about their history of self-mutilation. Of the 91% with a history of
      self mutilation, 32.8% reported first harming themselves as children (12 years of
      age or younger), 30.2% as adolescents (13-17 years of age), and 37% as adults (18
      or older). Using logistic regression analyses and controlling for baseline age,
      it was found that those with a childhood onset reported more episodes of self
      harm, a longer duration of self-harm, and a greater number of methods of self
      harm than either those with an adolescent or adult onset to their self
      mutilation. The results of this study suggest that a sizable minority of
      borderline patients first engage in self-harm as children and that the course of
      their self-mutilation may be particularly malignant.

PMID- 16563077
TI  - Internalization of the therapeutic process: differences between borderline and
      neurotic patients.
AB  - Intersession process in psychotherapy refers to the thoughts, memories, and
      feelings about each other and about their therapy sessions that participants
      experience during the intervals between sessions. This study compared the
      intersession process experienced by patients who had been diagnosed with severe
      borderline personality disorders (BPD) with others who had not. A total of 76
      patients with neurotic disturbances and 20 patients with BPD were treated in a
      therapeutic day clinic and completed the Intersession Experience Questionnaire
      (IEQ) before sessions of individual psychotherapy and the Session Questionnaire
      (Stundenbogen) after those sessions. Comparison of the two groups on these
      measures of intersession process and postsession outcome showed markedly
      different patterns in patients' evaluations and internalizations of in-session
      therapeutic experiences: most prominently, that BPD patients internalize therapy
      sessions with much more negative and contradictory emotions.

PMID- 16563076
TI  - The relation of neediness and Axis II pathology.
AB  - Neediness, as a maladaptive form of interpersonal dependency, has been implicated
      in a range of psychopathology, most commonly mood and personality disorders. In
      light of the literature's sparse and inconsistent findings, Bornstein,
      Hilsenroth, Padawer, and Fowler (2000) have called for a systematic evaluation of
      dependency's role across the spectrum of Axis II disorders. The current study of
      individuals without current or past Axis I diagnoses found that Neediness was
      significantly related to dimensions of dependent, borderline, and histrionic
      personality disorders. Implications for the assessment of interpersonal
      dependency and issues in need of further clarification are highlighted.

PMID- 16563078
TI  - Reduced Self-Referential Source Memory Performance is Associated with
      Interpersonal Dysfunction in Borderline Personality Disorder.
AB  - Source memory is impaired in schizophrenia, and this deficit is related to
      symptoms of interpersonal antagonism such as suspiciousness and hostility. The
      present study evaluated source memory in borderline personality disorder (BPD)
      and its relation to interpersonal antagonism. Forty-one noninpatient adults with
      BPD according to the DSM-IV and 26 healthy control subjects performed a verbal
      source memory test requiring completion of sentences with and without emotional
      content ("Hot" vs. "Cold" sentences). Subjects also completed self-report
      measures of suspiciousness and interpersonal antagonism (Buss-Durkee Hostility
      Inventory) and depression (Beck Depression Inventory). The BPD group showed no
      significant difference from the control group in self-referential source memory,
      recognition memory, response bias, and performance enhancement for items with
      emotion content. However, in the BPD group, poorer self-referential source memory
      was significantly related to Hostility measures including suspiciousness, but not
      with Depression scores. In contrast, generic item recognition memory was
      unrelated to Hostility. Heterogeneity in source memory function may be
      specifically related to some of the hallmark interpersonal disturbances of BPD,
      independent of the effects of general negative affect or general memory
      impairment.

PMID- 16563079
TI  - The impact of borderline personality disorder and anxiety on neuropsychological
      performance in major depression.
AB  - Previous studies of neuropsychological performance in borderline personality
      disorder (BPD) have exhibited mixed results. The high rate of co-occurring major
      depressive disorder (MDD) in BPD makes it difficult to specify whether
      neuropsychological deficits in BPD predominantly reflect co-occurring MDD or
      unique aspects of their psychopathology. To address this issue, 22 participants
      with borderline personality disorder and concurrent major depressive disorder
      (BPD-MDD) and 33 participants with MDD and no concurrent personality disorder
      were compared on a neuropsychological battery that assessed seven domains of
      performance: general intellectual functioning, motor skill, psychomotor speed,
      attention, memory, working memory, and executive function. Neuropsychological
      performance did not differ between BPD-MDD and MDD. However, BPD-MDD participants
      reported higher levels of anger, anxiety, and of overall emotional distress
      compared to MDD. When levels of anxiety were controlled, BPD-MDD participants
      exhibited superior general intellectual performance, psychomotor speed, and
      attention. Deficits found in previous BPD samples may reflect their
      susceptibility to co-occurring MDD. The impact of anxiety on neuropsychological
      performance in BPD, though, indicates a need for future experimental studies of
      the effects of mood on cognitive function to determine whether mood
      dysregulation, rather than core depressive symptoms, underlie cognition
      impairments in BPD.

PMID- 16563080
TI  - Obesity and obesity-related illnesses in borderline patients.
AB  - The purpose of this study was to examine the prevalence, risk factors, and
      consequences of obesity in borderline patients 6 years after an index admission
      for psychiatric reasons. Two hundred and sixty-four borderline patients who met
      Revised Diagnostic Interview for Borderlines (DIB-R; Zanarini, Gunderson,
      Frankenburg, & Chauncy, 1989) and Diagnostic and Statistical Manual of Mental
      Disorders (3rd ed. ref.) (DSM-III-R; APA, 1987) criteria for BPD were interviewed
      concerning their body mass index (BMI) and related medical problems. Seventy-four
      of the 264 borderline patients at 6-year follow up were obese, having a BMI > or
      = 30 kg/m2. They were significantly more likely than the nonobese patients to
      report suffering from diabetes, hypertension, osteoarthritis, chronic back pain,
      carpal tunnel syndrome, urinary incontinence, gastroesophageal reflux disorder,
      gallstones, and asthma. Four significant risk factors were found: chronic PTSD,
      lack of exercise, a family history of obesity, and a recent history of
      psychotropic polypharmacy. These results suggest that obesity is common among
      heavily treated borderline patients and is associated with a number of chronic
      medical disorders.

PMID- 16563081
TI  - The Dutch DAPP-BQ: improvements, lower- and higher-order dimensions, and
      relationship with the 5DPT.
AB  - After modifying 53 items in a previous Dutch translation of the Dimensional
      Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ; Livesley &
      Jackson, 2002), the present DAPP-BQ scales (with or without Self-Harm included)
      were subjected to a principal components analysis with oblimin or varimax
      rotation in a general population sample of 478 subjects, retaining four factors.
      All four (higherorder) factors (Emotional Dysregulation, Dissocial, Inhibition,
      and Compulsivity) proved identical to the factors originally derived in Canada,
      with Tucker coefficients of factor similarity approaching unity. Particularly the
      (unexpected) finding that the present Dutch version of the DAPP-BQ also resulted
      in an Inhibition factor (and not, like the former Dutch version, in an Intimacy
      Problems factor) was considered positive. In addition, a principal components
      analysis with oblimin rotation was conducted on the 282 items contained in the 18
      DAPP-BQ scales, investigating the lower-order structure of the DAPP-BQ; in this
      case, 18 factors were retained. Although the structure originally derived by
      Livesley and colleagues could not be recovered completely, the degree of
      similarity was of such a magnitude that the 18 DAPP-BQ scales were considered to
      give a dependable account of the "true" lower-order structure of disordered
      personality. Moreover, based on the finding that the 18 scales are sufficiently
      reliable (Cronbach's alpha) and correlate as predicted in a subsample of 284
      subjects with the normal personality scales of Van Kampen's 5DPT (or, Five
      Dimensional Personality Test), the DAPP-BQ appears to be a valuable instrument.

PMID- 16563083
TI  - The future of cancer prevention: ripe for a revolution.

PMID- 16563082
TI  - Co-occurrence of personality disorders with mood, anxiety, and substance use
      disorders in a young adult population.
AB  - The purpose of this study was to determine the co-occurrence of DSM- III-R
      personality disorders (PDs) with mood, anxiety, and substance use disorders in a
      young adult population. The members of the Northern Finland 1966 Birth Cohort
      Project, living in the city of Oulu with an age of 31 years (N = 1,609) were
      invited to participate in a two-phase field study. The SCID I and II were used as
      diagnostic instruments. One hundred and seventy-seven out of 321 interviewed
      subjects met the criteria for mood, anxiety, or substance use disorders.
      Altogether 72 (41%) of the subjects with an Axis I disorder met the criteria for
      at least one PD. The weighted co-occurrence rate of any PD varied from 28% for
      mood disorders to 47% for anxiety disorders. PDs, especially those in Cluster C,
      are highly associated with Axis I psychiatric disorders in population.

PMID- 16563084
TI  - Erlotinib or capecitabine with gemcitabine in pancreatic cancer?

PMID- 16563086
TI  - Pentostatin and purine analogs for indolent lymphoid malignancies.
AB  - Pentostatin has been shown to be active in a variety of B- and T-cell
      malignancies. The drug is a tight inhibitor of adenosine deaminase, a key
      degradative enzyme of purine metabolism present in all human tissues, with the
      highest levels found in the lymphoid system. Early clinical trials indicated that
      this agent was highly active in acute lymphoblastic leukemias with high
      intracellular adenosine deaminase levels. Relatively high doses of the drug were
      needed, which was associated with severe adverse events. Through the efforts of a
      few investigators, better tolerated, low-dose regimens have been shown to be
      extremely active in lymphoproliferative diseases with very low intracellular
      adenosine deaminase levels such as hairy cell leukemia, B- and T-cell chronic
      leukemias, T-cell cutaneous lymphomas and low-grade non-Hodgkin lymphomas.
      Clinical as well as experimental data have indicated that this drug induces
      lymphocyte-specific cytotoxicity, and myelosuppressive adverse events have been
      minimal. Although all the purine analogs have shown similar activity, the
      advantage of pentostatin is the relatively specific cytotoxicity against
      lymphocytes, which permits treatment even in patients with severe cytopenias.
      Although no direct comparisons of the purine analogs have been performed,
      pentostatin may be preferred due to this property.

PMID- 16563087
TI  - TGF-beta in cancer and other diseases.

PMID- 16563088
TI  - Photolyases: capturing the light to battle skin cancer.
AB  - Photolyases comprise efficient enzymes to remove the major UV-induced DNA
      lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs).
      While photolyases are present in all three kingdoms of life (i.e., bacteria,
      prokaryotes and eukaryotes), placental mammals appear to have lost these enzymes
      when they diverted from marsupials during evolution. Consequently, man and mice
      have to rely solely on the more complex and, for these lesions, less efficient
      nucleotide excision repair (NER) system. To assess the relative contribution of
      CPDs and 6-4PPs to the cytotoxic and genotoxic effects of the UV component of
      sunlight, we have recently generated a comprehensive set of transgenic mice
      expressing CPD and/or 6-4PP photolyases. Here, we discuss the use of photolyase
      transgenic mice as effective tools to study the adverse effects of UV
      irradiation.

PMID- 16563089
TI  - What do, can and should we learn from models to evaluate potential anticancer
      agents?
AB  - Transfer of new anticancer agents from bench to clinical trial takes in excess of
      10 years and costs up to US $500 million. Despite this massive commitment, many
      more new agents fail in the clinical trials than are successful. The poor
      performance of many investigational anticancer agents in the clinic implies that
      the preclinical models used to evaluate them are flawed, inappropriately used or
      the information they generate is misinterpreted. This article reviews current
      practice and the range of preclinical models available. The author provides a
      personal perspective on what information is needed and how in the future this
      might best be obtained from preclinical models to more effectively inform the
      transfer of novel, active agents into clinical practice.

PMID- 16563090
TI  - Phytanic acid, AMACR and prostate cancer risk.
AB  - The growing body of knowledge in cancer prevention demonstrates that for many
      cancers, risk must be defined in terms of both environmental and genetic factors.
      In prostate cancer, there is increasing evidence linking risk with polymorphisms
      in the alpha-methylacyl-CoA racemase (AMACR) gene and branched-chain fatty acids
      derived from specific sources of dietary fats. We are now at the point where we
      can begin to conceptualize possible inter-relationships between dietary and
      genetic risk as applied to prostate cancer, with the goal of generating testable
      hypotheses amenable to coordinated examinations. A greater understanding of such
      relationships should provide better ways to establish overall risk, to screen for
      the disease and perhaps to offer specific opportunities for prevention and
      treatment.

PMID- 16563091
TI  - Links between Propionibacterium acnes and prostate cancer.
AB  - Incidental foci of prostate cancer are found at autopsy in 30% of men in their
      third decade, and by their eighth decade more than 75% have histological evidence
      of cancer. This unprecedented cancer prevalence points to a ubiquitous causative
      agent or perhaps an interaction between multiple common carcinogenic cofactors.
      We propose that one of these carcinogens is Propionibacterium acnes. Several
      characteristics of prostate cancer suggest the involvement of an infectious agent
      and we provide evidence that P. acnes is an excellent candidate. We have cultured
      P. acnes from a substantial proportion of prostate glands containing cancer and
      shown a significant positive association with prostatic inflammation. P. acnes is
      well suited to cause persistent, low-grade infection involving a marked
      inflammatory response and the P. acnes subtypes most frequently associated with
      prostate cancer become highly prevalent in the urinary tract of males following
      puberty.

PMID- 16563092
TI  - Common genetic polymorphisms and prognosis of sporadic cancers: prostate cancer
      as a model.
AB  - To date, most molecular epidemiological studies on gene polymorphisms in cancer
      have focused on the risk of development and susceptibility to cancer. However,
      interindividual genetic variation may contribute greatly to the treatment outcome
      and prognosis of cancer by affecting the interaction between cancer cells and
      hormones, growth factors and factors influencing the tumor microenvironment. In
      prostate cancer, several recent molecular epidemiological studies suggested the
      possibility of predicting treatment outcome and prognosis using genetic
      polymorphisms. Candidate genes are hormone-related, oncogenes, tumor-suppressor
      and cell cycle-growth control-related genes, as well as genes related to immune
      response, inflammatory change, neovasculization, and the extracellular matrix,
      genes involved in drug and xenobiotic metabolism and genes involved in DNA repair
      and genome stability. There remain a huge number of candidate genes whose
      polymorphisms may affect the progression and treatment outcome of various kinds
      of cancer, including that of prostate cancer.

PMID- 16563093
TI  - The role of p53 mutations as a prognostic factor and therapeutic target in
      inflammatory breast cancer.
AB  - Inflammatory breast cancer is a rare but lethal form of locally advanced breast
      cancer. Despite improvements in survival with the advent of multidisciplinary
      treatment regimens, 5-year survival rates remain disappointing, at approximately
      30%. Numerous molecular markers have been investigated for their potential as
      useful prognostic and predictive markers of treatment response that would impact
      on the management of inflammatory breast cancer. This review discusses the
      current status of p53 mutations both as a prognostic marker and as a potential
      target for directed therapies.

PMID- 16563094
TI  - Risk prediction models for familial breast cancer.
AB  - A positive family history of breast cancer, reflecting genetic susceptibility, is
      one of the strongest risk factors for the disease. A number of breast cancer
      susceptibility genes have been identified to date, with the most important being
      BRCA1 and BRCA2. Risk prediction models can be used to identify individuals
      likely to carry BRCA1 and BRCA2 mutations and individuals at high risk of
      developing the disease. This information can then be used to target genetic
      testing, screening and interventions more effectively. In this article, the
      authors review the risk models that have been developed for familial breast
      cancer and discuss their applicability, strengths and weaknesses, and present
      examples of classifying women into risk categories according to the predictions
      by the various models. The review concludes with a discussion of the ways in
      which risk models could be improved in the immediate- and long-term future.

PMID- 16563095
TI  - Nitric oxide and hormones in breast cancer: allies or enemies?
AB  - Unlike other types of cancer, tumors of the breast are greatly influenced by
      steroid hormones. The effect of estrogen and progesterone depends on the presence
      of their specific receptors and these constitute important parameters in
      determining the aggressiveness of the tumor, the feasibility of certain therapies
      and the prediction of relapse. The molecular mechanisms of steroid hormone action
      have not been fully elucidated but recent findings implicate the nitric oxide
      (NO) pathway in some of these effects. Both hormones can regulate the nitric
      oxide synthases (NOS) and, in turn, the NO produced has profound consequences on
      tumor cell homeostasis. On one hand, estrogen increases the activity of
      endothelial NOS (eNOS or NOSIII), while progesterone activates inducible NOS
      (iNOS or NOSII) expression. The data presented suggest that the low levels of NO
      produced by NOSIII mediate the proliferative effect of estrogen. On the other
      hand, the increase in apoptosis in response to progesterone could implicate the
      high levels of NO produced by induction of NOSII expression. Understanding of the
      mechanisms and interactions of steroid hormones with the NO pathway could lead to
      the development of new approaches and strategies for the effective treatment of
      breast cancer.

PMID- 16563096
TI  - Tailor-made chemotherapy for non-small cell lung cancer patients.
AB  - The selection of the most effective chemotherapy treatment based on evaluation of
      biomarkers, that is, 'tailor-made chemotherapy', can improve the clinical outcome
      of non-small cell lung cancer patients, including early-stage tumors with a high
      metastatic potential and advanced-stage tumors with a low proliferation rate.
      Therefore, treatment would be chosen according to which drugs would be most
      effective in combating specific tumors. For example: 5-fluorouracil-derived
      agents would be used for tumors with a low expression of thymidylate synthase;
      gefitinib and erlotinib for tumors with epidermal growth factor receptor (EGFR)
      mutations or increased EGFR gene copy numbers; cisplatin and carboplatin for
      tumors with a low expression of excision repair cross complementing-1; and
      gemcitabine for tumors with a low expression of ribonucleotide reductase. The
      remaining populations of non-small cell lung cancers require chemotherapy using
      other drugs based on an evaluation of other targeted molecules.

PMID- 16563097
TI  - Viral immunoreceptor-associated tyrosine-based activation motifs: potential
      players in oncogenesis.
AB  - Cancer is thought to arise as a consequence of multiple insults to a cell.
      Mutations that lead to increased expression or activity of proto-oncogenes or
      decreased expression of tumor suppressors are common insults that have been
      identified to date. However, when considering tumor viruses, viral proteins that
      modify cellular gene expression, alter host immune surveillance, or affect
      signaling pathways are also common players. Notably, several of these tumor
      viruses encode proteins containing an immunoreceptor-associated tyrosine-based
      activation motif (ITAM), a signaling motif recently implicated in epithelial cell
      oncogenesis. As expression of proteins bearing this motif is normally restricted
      to hematopoietic cells, recent work highlighting the consequences of ITAM
      expression in epithelial cells suggests it may play a role in solid tumor
      formation.

PMID- 16563098
TI  - Vasopressors in cardiac arrest: we may never know!

PMID- 16563100
TI  - Life without the PA catheter.

PMID- 16563101
TI  - Managing septic acute renal failure: "fill and spill"? "squeeze and diurese"? or
      "block Bax to the max"?

PMID- 16563102
TI  - Diagnosis and management of acute pancreatitis.
AB  - OBJECTIVE: To review the diagnosis and management of patients with acute
      pancreatitis. DATA SOURCES: A review of articles reporting on the diagnosis and
      management of acute pancreatitis. SUMMARY OF REVIEW: Acute pancreatitis is an
      acute inflammatory disorder of the pancreas caused by an intracellular activation
      of pancreatic digestive enzymes. The destruction of pancreatic parenchyma induces
      a systemic activation of coagulation, kinin, complement and fibrinolytic cascades
      with liberation of cytokines and reactive oxygen metabolites which, if severe and
      overwhelming, can lead to shock, acute renal failure and the acute respiratory
      distress syndrome. In approximately 45% of cases the disorder is associated with
      cholelithiasis, with ethanol abuse accounting for a further 35% of patients. In
      10% of patients no cause may be found. In 85-90% of patients, acute pancreatitis
      is self-limiting and subsides spontaneously within 4-7 days. Specific treatment
      for acute pancreatitis currently does not exist and management is still
      supportive, with therapy aimed at reducing pancreatic secretion, replacing fluid
      and electrolytes losses and analgesia. All patients with severe acute
      pancreatitis who have one (or more) organ failures (e.g. circulatory, pulmonary
      or renal) should be managed in an intensive care unit with mechanical
      ventilation, inotropic agents and renal replacement therapy being used to manage
      organ failure. In selected circumstances, endoscopic retrograde
      cholangiopancreatography (ERCP), antibiotics and surgical drainage are used. For
      example, ERCP will reduce morbidity in patients with ampullary or common bile
      duct stones associated with acute pancreatitis, if obstructive jaundice or
      cholangitis are present. Prophylactic antibiotics (e.g. imipenem 500 mg i.v. 8
      hourly for 7-10 days with fluconazole 400 mg i.v. daily) will reduce the
      incidence of pancreatic infection in patients with severe acute pancreatitis with
      pancreatic necrosis, and surgical intervention in severe acute pancreatitis,
      while rarely used, in patients who have a progressively increasing inflammatory
      mass and worsening multi-system organ failure, necrosectomy with open or closed
      drainage may be required. CONCLUSIONS: Acute pancreatitis is a benign abdominal
      disorder in up to 85% of cases. In the remaining 10%-15% of cases the disorder is
      life threatening with management of the disorder requiring admission to an
      intensive care unit with cardiovascular, respiratory, and renal monitoring and
      support.

PMID- 16563103
TI  - Diltiazem overdose haemodynamic response to hyperinsulinaemia-euglycaemia
      therapy: a case report.
AB  - A 59-year-old woman was admitted to the intensive care unit after ingesting 5.76
      g of an extended release preparation of diltiazem. The patient was hypotensive
      and bradycardic and was treated initially with intravenous fluids, adrenaline,
      noradrenaline, vasopressin and standard insulin doses to maintain the blood
      glucose levels between 6-10 mmol/L. As the patient remained inotrope dependent
      the insulin dose was increased to 25 U/hr with an infusion of 50% dextrose to
      maintain the blood glucose levels between 6-8 mmol/L. Within 30 minutes, the mean
      arterial pressure increased from 65 mmHg to 80 mmHg and within 60 minutes all
      vasoactive agents were discontinued. A right heart catheter inserted before the
      increased dose of insulin revealed that the predominant haemodynamic effect of
      the hyperinsulinaemia-euglycaemia therapy appeared to be an increase in the
      peripheral vascular resistance.

PMID- 16563104
TI  - Current concepts in the management of heart failure.
AB  - OBJECTIVE: To review current concepts in the management of patients with heart
      failure. DATA SOURCES: A review of articles reported on acute and chronic heart
      failure. SUMMARY OF REVIEW: Heart failure has been defined as that state which
      occurs when the heart fails to maintain the needs of the body despite a
      satisfactory venous return. While it has been divided functionally into high
      output failure and low-output failure, it is often used to describe patients with
      left ventricular low-output failure and is divided into systolic or diastolic
      heart failure, depending on left ventricular ejection fraction. The clinical
      features are due largely to venous congestion and reduction in cardiac output
      with symptoms of fatigue, orthopnoea, paroxysmal nocturnal dyspnoea and
      peripheral oedema being common complaints. Plasma natriuretic peptide levels are
      elevated in patients with symptomless left ventricular failure and have been
      useful in diagnosing heart failure in patients admitted with acute dyspnea.
      Treatment of heart failure is aimed at correcting both the underlying disorder as
      well as the precipitating cause (e.g. ischaemia, valvular heart disease, anaemia,
      thyrotoxicosis, etc), as well as reducing cardiac work, enhancing myocardial
      contractility and treating the complications (e.g. reducing salt and water
      retention, and neurohumoral activation). Angiotensin converting enzyme (ACE)
      inhibitors, angiotensin receptor antagonists, beta-blockers and spironolactone
      have all been associated with a reduction in mortality in patients with chronic
      heart failure. While digoxin and diuretics are used to reduce the number of
      episodes of pulmonary oedema, they have not been associated with a significant
      reduction in mortality. Surgery (e.g. transplantation, mechanical assist devices)
      has a definite place in young patients with chronic dilated cardiomyopathy with
      severe heart failure although other therapeutic agents (e.g. growth hormone,
      thyroxine and antioxidants) are yet to be shown to be of benefit. CONCLUSIONS:
      Heart failure is a common condition caused by many disorders leading to left
      ventricular dysfunction. Management of the underlying disorder (e.g. ischaemia,
      valvular disease, hypertension) maintenance of sinus rhythm, as well as reducing
      excessive neurohumoral activation (ACE inhibitors, angiotensin receptor
      antagonists, beta-blockers, spironolactone) can reduce mortality and improve
      morbidity in patients with chronic heart failure.

PMID- 16563105
TI  - Aetiology and management of acute cardiac tamponade.
AB  - OBJECTIVE: To review current concepts in the aetiology and management of patients
      with cardiac tamponade. DATA SOURCES: A review of articles reported on acute
      cardiac tamponade. SUMMARY OF REVIEW: Cardiac tamponade is defined as a
      haemodynamically significant cardiac compression caused by pericardial fluid. The
      fluid may be blood, pus, effusion (transudate or exudate) or air and treatment
      involves correction of the cardiac diastolic restriction by removing pericardial
      fluid during either pericardiocentesis or thoracotomy. Pericardiocentesis is
      usually performed for urgent management of an acute tamponade. A thoracotomy is
      required when a tamponade exists following coronary artery bypass grafting,
      cardiac rupture, penetrating or closed cardiac trauma and aortic dissection or
      where a pericardial clot is likely. Removal of pericardial fluid by percutaneous
      catheterisation of the pericardial sac traditionally uses the subxiphoid 'blind'
      approach., However, pericardial aspiration is often currently performed under
      transthoracic echocardiographic guidance with the commonest site of needle entry
      being on the chest wall at or near the apex and the needle directed perpendicular
      to the skin. The pericardial fluid is drained using an indwelling 'pigtail'
      catheter, preferably with close monitoring of the pulmonary artery wedge
      pressure, as rapid removal of large volumes of pericardial fluid (> 500 mL) may
      result in a 'decompressive syndrome' causing pulmonary oedema. The fluid is sent
      for culture and Gram-stain and analysed for glucose, protein, lactate
      dehydrogenase, haemoglobin and white cell count. If appropriate the fluid is also
      analysed for amylase, and cholesterol and sent for cytology, serology and
      parasitic studies and viral, mycobacterial and fungal cultures. CONCLUSIONS:
      Cardiac tamponade may present as an acute or subacute syndrome of elevated
      central venous pressure and hypotension. Pericardiocentesis using
      echocardiographic guidance and right heart catheter control is often the method
      of choice for acute removal of fluid.

PMID- 16563106
TI  - Quantifying cerebral autoregulation in health and disease.
AB  - OBJECTIVE: To review methods of quantifying human cerebral autoregulation in
      health and disease. DATA SOURCES: Articles and published abstracts on methods to
      quantify cerebral autoregulation in health and disease. SUMMARY OF REVIEW:
      Cerebral autoregulation is defined as the relationship between cerebral blood
      flow and cerebral perfusion pressure. Complex neurohumoral processes are involved
      in myogenic and metabolic mechanisms to maintain cerebral blood flow at a
      constant level in the presence of fluctuating systemic and cerebral perfusion
      pressures. Despite advances in physiological measurement, there is no standard
      measurement of cerebral blood flow and quantifying cerebral autoregulation
      remains problematic. Clinical monitors such as transcranial Doppler and jugular
      bulb oximetry have high levels of error with poor specificity and sensitivity.
      Cerebral autoregulation is impaired in traumatic brain injury and subarachnoid
      haemorrhage, so that cerebral blood flow becomes pressure-passive. Hypotension is
      associated with significant secondary neuronal damage following traumatic brain
      injury. Hypertensive emergencies represent failure of the upper autoregulatory
      threshold, often with devastating neurological consequences. The monitoring and
      treatment of autoregulatory failure remains limited and is essentially directed
      at maintaining an appropriate systemic blood pressure. Consequently, the use of
      strategies to manipulate cerebral perfusion requires care and circumspection.
      CONCLUSIONS: Cerebral autoregulation is impaired with brain injury with cerebral
      blood flow often becoming pressure-passive. The monitoring and treatment of
      autoregulatory failure is limited and usually directed at maintaining systemic
      blood pressure with the effectiveness of this strategy often being unknown.

PMID- 16563107
TI  - Futility and its cost in the management of the critically ill patient.

PMID- 16563108
TI  - An 83-year-old man admitted to hospital drowsy, confused, hypotensive and with
      generalised rigidity.

PMID- 16563109
TI  - "I gave her a litre of saline and then some frusemide to 'kick' the kidneys
      along".

PMID- 16563110
TI  - Selective digestive decontamination: once again.

PMID- 16563111
TI  - Immunonutrition--a proven treatment for perioperative patients or an interesting
      idea in search of data?

PMID- 16563112
TI  - Illicit drugs--the dark before an Australian DAWN?

PMID- 16563113
TI  - Early revascularisation in acute myocardial infarction: beyond concept and into
      practice.

PMID- 16563114
TI  - Drug related admissions to intensive care: the role of illicit drugs and self
      poisoning.
AB  - OBJECTIVE: Drug related problems are a major consumer of healthcare, although
      little is known about the impact of self-poisoning and illicit drug use on the
      provision of intensive care. We wished to quantify the number of admissions to
      our intensive care unit that were attributable to self-poisoning and illicit drug
      use, and to identify issues related to recognition, follow-up, prevention and
      cost. METHODS: A retrospective review of all admissions to Liverpool hospital
      intensive care unit for the year 2000. All admissions with non-alcohol drug
      related causes or associations were reviewed and data relating to demographics,
      reason for admission, drugs taken, length of intensive care unit stay,
      interventions by Drug and Alcohol and Psychiatry services, follow-up and outcome
      were obtained. RESULTS: Of the 1790 patients admitted to the intensive care unit
      during the study period, 108 (6%) were non-alcohol drug-related. These admissions
      accounted for 407 intensive care unit bed days (5% of total intensive care unit
      bed days) and approximated to 10% of the intensive care unit budget for the year
      2000. The majority of patients were male (66%), with a mean age of 33 years. Drug
      overdose was the most common reason for admission (80%), followed by drug related
      traumatic injury (16%). The most common drug classes involved were the
      benzodiazepines, followed by the opiates and tricyclic antidepressants. The
      majority of patients (65%) had used more than one drug. Thirty-two patients (30%)
      did not return to their previous functioning level by the time of their discharge
      from hospital, and 13 of these (12% overall) required full-time nursing care.
      There were two deaths (2%) as a direct result of illicit drug use or self
      poisoning. The hospital Drug and Alcohol or Psychiatry services reviewed 78
      patients (72%) as inpatients, and 3 patients (3%) after discharge. Self-discharge
      or patient refusal to be reviewed by these services occurred in 13 (12%) cases.
      Twelve patients (11%) were not assessed by these services and were either
      reviewed by the admitting team or returned to the care of their family
      practitioner. CONCLUSIONS: Drug related problems account for a significant number
      of preventable admissions to intensive care unit every year. The mortality is
      low, but the cost to the community is high, as represented by the high level of
      morbidity and dependence on medical care.

PMID- 16563115
TI  - Early invasive revascularisation for patients critically ill after acute
      myocardial infarction: impact on outcome and ICU resource utilisation.
AB  - OBJECTIVE: To assess the value of early invasive revascularization for the
      initial management of critically ill patients after acute myocardial infarction
      in the daily practice of a University-affiliated referral hospital and to gauge
      the impact of such a strategy on the intensive care unit. PATIENTS AND METHODS: A
      prospective observational study on all patients admitted to the Royal North Shore
      hospital who had acute pulmonary oedema and/or shock prior to acute angiography
      for acute myocardial infarction from January 1(st), 1998 to December 31, 2001.
      RESULTS: During the study period 846 patients with acute myocardial infarction
      had coronary artery angiography, 139 had acute pulmonary oedema and/or shock
      prior to angiography. The average age was 70 years, 65% of whom were male.
      Approximately 70% of these patients were admitted to the intensive care unit and
      coronary artery bypass surgery was performed on 38%. Of those patients admitted
      to the intensive care unit, 95% required mechanical ventilation, 81% required
      inotropic support and 50% required intra-aortic Balloon counterpulsation. In
      hospital mortality was 32%, 6 weeks mortality was 38% and 6 month mortality was
      42%. CONCLUSIONS: Our results confirm the benefit of early invasive
      revascularisation for critically ill patients after acute myocardial infarction
      although a substantial amount of intensive care unit resources and cardiothoracic
      surgical expertise were required.

PMID- 16563116
TI  - Remember the side effects of haloperidol: a case report.
AB  - An eighteen-year-old man who had a laminectomy and subtotal excision of a
      lipomyelomeningocele, received a single dose of haloperidol for post-operative
      pain and agitation. The patient suffered an acute dystonic reaction and was
      extensively investigated before the correct diagnosis and treatment was
      instituted. This case illustrates the ease with which extrapyramidal side effects
      following treatment with haloperidol may be overlooked in complicated medical or
      surgical cases.

PMID- 16563117
TI  - Catecholamines in the treatment of septic shock: effects beyond perfusion.
AB  - OBJECTIVE: To review the metabolic effects of sympathomimetic agents in the
      septic patient. DATA SOURCES: A review of articles reported on the metabolic
      effects of the commonly used sympatho-mimetic agents in the critically ill
      patient. SUMMARY OF REVIEW: Sepsis and septic shock are clinically charcterized
      mainly by derangements of cardiocirculatory function. Mainstay therapeutic
      interventions for haemodynamic stabilisation are adequate volume resuscitation
      and vasoactive agents. These, however, may be linked with additional effects on
      energy balance and cell metabolism. As well as the haemodynamic effects, specific
      metabolic effects need to be considered for optimal vasopressor treatment during
      severe sepsis and septic shock. This review highlights the typical haemodynamic
      and metabolic alterations associated with the commonly used sympathomimetic drugs
      in these conditions. CONCLUSIONS: Sepsis and septic shock are linked with
      profound metabolic alterations. An additional impact of vasoactive therapy on
      metabolism has to be taken into account when using these agents to treat severe
      sepsis and septic shock.

PMID- 16563118
TI  - The role of immune-enhancing diets in the management of perioperative patients.
AB  - OBJECTIVE: To review the effects of immunonutrients in the perioperative patient.
      DATA SOURCES: Articles and published peer-review abstracts of studies reported on
      immune enhancing diets in patients during the perioperative period. SUMMARY OF
      REVIEW: Enteral nutrition is the method of choice for substrate supplementation
      in patients with a normal gastrointestinal tract but who are otherWise unable to
      eat normally. It is also a safer, more practical and less expensive alternative
      to the parenteral route and is now being used successfully in previously
      contraindicated conditions including pancreatitis and major abdominal trauma.
      Advances in enteral nutrition include the development of immunonutrients which
      have been used to attenuate the adverse effects of starvation, illness and
      surgery on the architecture and function of the gastrointestinal tract,
      implicated in the development of multiple organ dysfunction syndrome. These
      agents stimulate immune function and are potentially an effective strategy in
      improving the outcome in the peri-operative period by reducing post-operative
      infections and length of hospital stay. CONCLUSIONS: Immunonutrition confers an
      additive benefit when compared with standard enteral and parenteral nutrient
      preparations in the management of perioperative malnourished patients. What is
      less clear is at what severity of illness this benefit begins, whether there is a
      significant reduction in mortality and at what point the cost benefit in the
      reduction in complications no longer occurs.

PMID- 16563119
TI  - Designing 'balanced' crystalloids.
AB  - OBJECTIVE: To present a rationale for the design of balanced resuscitation and
      renal replacement crystalloids based on Stewart's physical chemical approach to
      acid-base. DATA SOURCES: Articles and published abstracts on acid-base
      physiology, crystalloid infusions and renal replacement therapy. SUMMARY OF
      REVIEW: Although it is uncertain that crystalloid-induced metabolic acidosis
      causes significant harm, Stewart's approach assists in designing balanced fluids
      without this side effect. In his analysis, the three independent variables
      determining acid-base balance are PCO2, the total concentration of non-volatile
      weak acid (A(TOT)) and the strong ion difference (SID). Raising and lowering
      A(TOT) while holding SID constant cause a metabolic acidosis and alkalosis
      respectively. Lowering and raising plasma SID while clamping A(TOT) cause a
      metabolic acidosis and alkalosis respectively. The SID of a crystalloid is its
      [HCO3-], or that part of an organic bicarbonate surrogate which is metabolised on
      infusion. Rapid infusion alters plasma SID towards crystalloid SID, but also
      lowers A(TOT) by haemodilution. We have shown that the SID of a balanced infusion
      crystalloid is 24 mEq/L. This generates a fall in plasma SID precisely
      counteracting the A(TOT) dilutional alkalosis. In contrast, a balanced renal
      replacement crystalloid must generate a higher plasma SID appropriate for the
      existing A(TOT), since there is no dilution. If A(TOT) is low, as in
      hypoalbuminaemia, the balanced dialysis SID falls correspondingly. A further SID
      reduction is needed to counteract Donnan effects within the filter. CONCLUSIONS:
      A crystalloid SID of 24 mEq/L is 'balanced' for rapid intravenous administration.
      The 'balanced' SID of renal replacement fluids is likely to be significantly
      higher, although less than the normal plasma SID of 42 mEq/L.

PMID- 16563120
TI  - Mortality and other event rates: what do they tell us about performance?

PMID- 16563121
TI  - The Lancet is my hero; I shall not want.

PMID- 16563122
TI  - A 54 year old man with hypotension, abdominal pain and pyrexia.

PMID- 16563123
TI  - Peer review: standards, judgment and sweet charity.

PMID- 16563124
TI  - Sedation and agitation in the critically ill patient.

PMID- 16563126
TI  - The 1952-1953 Danish epidemic of poliomyelitis and Bjorn Ibsen.

PMID- 16563125
TI  - Equivalence trials and the treatment of fungal infections: correction.

PMID- 16563127
TI  - Blockage of oncostatin M-induced LDL receptor gene transcription by a dominant
      negative mutant of C/EBPbeta.
AB  - OM (oncostatin M) activates the human LDLR [LDL (low-density lipoprotein)
      receptor] gene transcription in HepG2 cells through the SIRE (sterol-independent
      regulatory element) of LDLR promoter. The SIRE sequence consists of a C/EBP
      (CCAAT/enhancer-binding protein)-binding site and a CRE (cAMP-response element).
      Our previous studies [Zhang, Ahlborn, Li, Kraemer and Liu (2002) J. Lipid Res.
      43, 1477-1485; Zhang, Lin, Abidi, Thiel and Liu (2003) J. Biol. Chem. 278, 44246
      44254] have demonstrated that OM transiently induces EGR-1 (early growth response
      gene product 1) expression and EGR-1 activates LDLR transcription primarily
      through a protein-protein interaction with C/EBPbeta, which serves as a co
      activator of EGR-1. In the present study, we examined the direct role of
      C/EBPbeta as a transactivator in OM-regulated LDLR gene transcription independent
      of EGR-1. We show that OM induces C/EBPbeta expression with kinetics slower than
      EGR-1 induction. A significant increase in C/EBPbeta protein level is detected by
      2 h of OM treatment and remains elevated for 24 h. Chromatin immunoprecipitation
      assays demonstrate that the amount of C/EBPbeta bound to the LDLR SIRE sequence
      is increased 2.8-fold of control by 2 h of OM treatment, reached the highest
      level of 8-fold by 4 h, and slowly declined thereafter. To further examine the
      requirement of C/EBPbeta in OM-stimulated LDLR expression, we developed a His
      tagged dominant-negative mutant of C/EBPbeta (His-C/EBPbeta-P4; where P4 is
      plasmid 4 in our mutation series), consisting of the DNA-binding and leucine
      zipper domains of C/EBPbeta (amino acids 246-345). Expression of His-C/EBPbeta-P4
      in HepG2 cells significantly diminishes the OM-induced increase in LDLR promoter
      activity and the elevation of endogenous LDLR mRNA expression. Taken together,
      these new findings identify C/EBPbeta as an OM-induced transactivator in LDLR
      gene transcription and provide a better understanding of the molecular mechanism
      underlying the sterol-independent regulation of LDLR expression.

PMID- 16563128
TI  - Aquaporin 2 (AQP2) and vasopressin type 2 receptor (V2R) endocytosis in kidney
      epithelial cells: AQP2 is located in 'endocytosis-resistant' membrane domains
      after vasopressin treatment.
AB  - BACKGROUND INFORMATION: Aquaporin 2 (AQP2) plays an important, VP (vasopressin)
      regulated role in water reabsorption by the kidney. The amount of AQP2 expressed
      at the surface of principal cells results from an equilibrium between the AQP2 in
      intracellular vesicles and the AQP2 on the plasma membrane. VP shifts the
      equilibrium in favour of the plasma membrane and this allows osmotic
      equilibration to occur between the collecting duct lumen and the interstitial
      space. Membrane accumulation of AQP2 could result from a VP-induced increase in
      exocytosis, a decrease in endocytosis, or both. In the present study, we further
      investigated AQP2 accumulation at the cell surface, and compared it with V2R (VP
      type 2 receptor) trafficking using cells that express epitope-tagged AQP2 and
      V2R. RESULTS: Endocytosis of V2R and of AQP2 are independent events that can be
      separated temporally and spatially. The burst of endocytosis seen after VP
      addition to target cells, when AQP2 accumulates at the cell surface, is primarily
      due to internalization of the V2R. Increased endocytosis is not induced by
      forskolin, which also induces membrane accumulation of AQP2 by direct stimulation
      of adenylate cyclase. This indicates that cAMP elevation is not the primary cause
      of the initial, VP-induced endocytic process. After VP exposure, AQP2 is not
      located in endosomes with internalized V2R. Instead, it remains at the cell
      surface in 'endocytosis-resistant' membrane domains, visualized by confocal
      imaging. After VP washout, AQP2 is progressively internalized with the fluid
      phase marker FITC-dextran, indicating that VP washout releases an endocytotic
      block that maintains AQP2 at the cell surface. Finally, polarized application of
      VP to filter-grown cells shows that apical VP can induce basolateral endocytosis
      and V2R down-regulation, and vice versa. CONCLUSIONS: After VP stimulation of
      renal epithelial cells, AQP2 accumulates at the cell surface, while the V2R is
      actively internalized. This endocytotic block may involve a reduced capacity of
      phosphorylated AQP2 to interact with components of the endocytotic machinery. In
      addition, a complex cross-talk exists between the apical and basolateral plasma
      membrane domains with respect to endocytosis and V2R down-regulation. This may be
      of physiological significance in down-regulating the VP response in the kidney in
      vivo.

PMID- 16563129
TI  - Ultrastructural changes of the carp (Cyprinus carpio) hepatocyte nucleolus during
      seasonal acclimatization.
AB  - BACKGROUND INFORMATION: The eurythermal fish carp (Cyprinus carpio) adjusts to
      the seasonal changes in the temperature and photoperiod of its habitat through
      diverse cellular and molecular mechanisms. We have observed that ribosomal
      biogenesis is modulated during the acclimatization process and correlates with
      profound phenotypic changes, reflecting a seasonal-dependent ultrastructural
      appearance of the nucleolar components. Previous studies using classical
      techniques showed that in winter-adapted carp the nucleolus appears to be
      segregated. In the present work, we have reassessed the nucleolar ultrastructural
      organization of the carp in summer- and winter-adapted fish by using more
      specific cytochemical and immunocytological techniques. RESULTS: The acetylation
      method provided evidence that the nucleolar organization is different between
      winter- and summer-adapted carp. In winter-adapted fish the fibrillar component
      appears as a unique mass surrounded by several granular caps, whereas in summer
      adapted carp the fibrillar component forms few cordons surrounded by granular
      masses. The nucleolar structure and distribution of the condensed chromatin
      observed varies upon seasonal acclimatization. In winter the nucleolar chromatin
      is densely packed in masses that surround the nucleolus, whereas during summer it
      displays a rather looser organization formed by filaments that not only surround
      the nucleolus, but also go through the nucleolar body. Using the TdT (terminal
      deoxynucleotidyl transferase)-immunogold labelling technique, we detected
      condensed and decondensed nucleolar chromatin, and found some labelling of
      fibrillar components in both seasons. When liver tissue from summer-adapted carp
      was treated with AMD (actinomycin D), we observed that the rearrangement of the
      nucleolar components and condensed chromatin were similar to that found in winter
      adapted fish, with differences in the distribution of the perinucleolar
      chromatin. CONCLUSIONS: The acetylation and TdT-immunogold labelling experiments
      indicated that the rearrangement of the nucleolar components of winter-adapted
      carp is very similar to the AMD-treated summer-adapted carp nucleolus, with the
      latter representing the repression of the ribosomal biogenesis that occurs during
      the cold season. Nevertheless, the distribution of the condensed perinucleolar
      chromatin in winter-adapted carp compared with AMD-treated cells suggests that
      the transcription of rRNA genes in winter-adapted fish is less strongly inhibited
      and does not lead to the classical segregation of the nucleolus of that described
      after AMD treatment. In addition, we have confirmed that carp hepatocyte nucleoli
      comprise only two main structural compartments: a fibrillar component and a
      granular component. Fibrillar centres were not observed.

PMID- 16563130
TI  - Complications and the learning curve for a laparoscopic nephrectomy at a single
      institution.
AB  - BACKGROUND: We assessed our experiences in performing a laparoscopic nephrectomy,
      with regard to complications and the learning curve, during a 4-year period.
      METHODS: Between November 2000 and October 2004, a total of 78 laparoscopic
      nephrectomies were performed at our institution (37 radical nephrectomies, 30
      nephroureterectomies and 11 simple nephrectomies). The patient charts were
      retrospectively reviewed to identify any operative and postoperative
      complications, and also to evaluate the operating time. RESULTS: A total of
      eleven complications (14.1%) occurred in our series (nine operative and two
      postoperative complications). All operative complications were due to vascular
      injuries (n=9), five (2.6%) of which required an open conversion. The operating
      time and the rates of complications decreased significantly as the surgeons'
      experiences increased. CONCLUSION: A laparoscopic nephrectomy could be performed
      as safely as previously reported. In addition, the learning curve for a
      laparoscopic nephrectomy appeared to be good over the initial 50 procedures at
      our institution.

PMID- 16563131
TI  - Comparison of the effectiveness and side-effects of tolterodine and oxybutynin in
      children with detrusor instability.
AB  - BACKGROUND: Treatment with anticholinergic agents is the mainstay of therapy for
      detrusor instability (DI), a chronic and morbid condition characterized by urge
      urinary incontinence. The aim of this study is to assess the effectiveness and
      tolerability of tolterodine and oxybutynin in children with DI. METHODS: A total
      of 60 children with DI were enrolled, 30 (14 male, 16 female, mean age 7.97+/
      2.71 years) in the tolterodine group and 30 (12 male, 18 female, mean age 7.33+/
      2.23 years) in the oxybutynin group. In this prospective study we reviewed data
      from 60 children followed for at least 6 months. All of the patients in the study
      population had a history of dysfunctional voiding. Urodynamic investigations were
      conducted in all of the patients before and after anticholinergic treatment.
      Episodes of urge urinary incontinence and adverse events were also evaluated.
      RESULTS: Improvements in urge incontinence episodes were similar for the children
      who received tolterodine or oxybutynin. Improvements in the urodynamic parameters
      were also the same in the two groups. Adverse events were significantly lower in
      the tolterodine group (13 events in 13 patients) compared to the oxybutynin group
      (27 events in 20 patients; P=0.027). CONCLUSION: Reductions in urge urinary
      incontinence episodes were similar with tolterodine and oxybutynin in children
      with DI. Side-effects were more common with oxybutynin. Treatment of children
      with DI with tolterodine shows significantly better tolerability and this may
      enhance children's compliance during long-term treatment.

PMID- 16563132
TI  - Do children with primary nocturnal enuresis have a retarded bone age? A cross
      sectional study.
AB  - OBJECTIVE: Nocturnal enuresis is a common pediatric problem, the etiology of
      which is unclear. In recent years, various studies have been published stating
      that children with nocturnal enuresis exhibit growth and skeletal maturation
      retardation. METHODS: In this cross-sectional study, we included 27 patients (16
      boys, 11 girls) between the ages of 6 and 14 years who had presented with primary
      nocturnal enuresis (PNE) complaints. We included in the evaluation 19 healthy
      subjects (12 boys, 7 girls), who were the siblings of the children with PNE, as
      the control group. RESULTS: The patients in both groups were similar in
      chronological age, bone age, height and weight, with no significant difference
      between groups (P>0.05). CONCLUSION: The two groups in our study consisted of the
      same genetic background. Thus, our results were found to be different from the
      previous studies. We have concluded that there is no direct relationship between
      enuresis nocturnal and skeletal maturation.

PMID- 16563133
TI  - Endoscope-assisted minilaparotomic radical retropubic prostatectomy.
AB  - OBJECTIVE: To assess the clinical efficacy of endoscope-assisted minilaparotomic
      radical retropubic prostatectomy (EAM-RRP) compared with conventional radical
      retropubic prostatectomy (cRRP). METHODS: From September 2001 to December 2003,
      30 patients with localized prostate cancer were treated by EAM-RRP. The surgical
      manipulation was performed through the wound with thoracoscopic assistance, using
      standard surgical instruments. In all cases, 800 mL of blood was collected from
      the patient for autotransfusion. For both EAM-RRP and cRRP, the internal iliac
      and obturator lymph nodes were dissected before the prostate removal. Clinical
      indicators such as operation time, blood loss, and duration of postoperative
      urine incontinence were analysed in the two groups. RESULTS: The postoperative
      period before ambulation and the duration of postoperative urine incontinence
      were significantly shorter after EAM-RRP than after cRRP, while no significant
      difference was found in operation time, blood loss, and duration of urethral
      catheterization. None of the cases required allotransfusion. CONCLUSION: EAM-RRP,
      which had a shorter postoperative period before ambulation and continence, is
      considered a safe and useful technique for radical prostatectomy.

PMID- 16563134
TI  - Four year clinical statistics of iridium-192 high dose rate brachytherapy.
AB  - BACKGROUND: We evaluated the efficacy and complications of high dose rate (HDR)
      brachytherapy using iridium-192 (192Ir) combined with external beam radiotherapy
      (EBRT) in patients with prostate cancer. METHODS: Ninety-seven patients underwent
      192Ir HDR brachytherapy combined with EBRT at our institution between February
      1999 and December 2003. Of these, 84 patients were analysed in the present study.
      192Ir was delivered three times over a period of 2 days, 6 Gy per time, for a
      total dose of 18 Gy. Interstitial application was followed by EBRT at a dose of
      44 Gy. Progression was defined as three consecutive prostate-specific antigen
      (PSA) rises after a nadir according to the American Society for Therapeutic
      Radiology and Oncology criteria. The results were classified into those for all
      patients and for patients who did not undergo adjuvant hormone therapy. RESULTS:
      The 4-year overall survival of all patients, the nonadjuvant hormone therapy
      group (NAHT) and the adjuvant hormone therapy group (AHT) was 87.2%, 100%, and
      70.1%, respectively. The PSA progression-free survival rate of all patients,
      NAHT, and AHT was 82.6%, 92.0%, and 66.6%, respectively. Of all patients, the 4
      year PSA progression-free survival rates of PSA<20 and PSA>or=20 groups were
      100%, and 46.8%, respectively. According to the T stage classification, PSA
      progression-free survival rates of T1c, T2, T3, and T4 were 100%, 82.8%, 100%,
      and 12.1%, respectively. Prostate-specific antigen progression-free survival
      rates of groups with Gleason scores (GS)<7 and GS>or=7 were 92.8% and 60.1%,
      respectively. Of NAHT, PSA progression-free survival of PSA<20 was 100% vs 46.8%
      for PSA>or=20, that of T1c was 100% vs 75% for T2, and that of GS<7 was 100% vs
      75% for GS>or=7. No significant intraoperative or postoperative complications
      requiring urgent treatment occurred except cerebellum infarction. CONCLUSIONS:
      192Ir HDR brachytherapy combined with EBRT was as effective as radical
      prostatectomy and had few associated complications.

PMID- 16563136
TI  - How frequent are invasive therapies required in patients receiving tamsulosin for
      benign prostatic hyperplasia? A retrospective long-term study.
AB  - Three hundred Japanese patients with benign prostatic hyperplasia (BPH) who
      started an alpha1-adrenoceptor blocker, tamsulosin, between 1993 and 1996 were
      followed for 3.0+/-3.3 years (mean+/-SD) to determine whether an association
      existed between the disease severities measured prior to the tamsulosin treatment
      and the timing at which the invasive therapy was implemented. Patients with a
      lower quality of life (QOL) index or maximum urinary flow rate (Qmax) were
      transferred for invasive therapy earlier than those with less severe BPH. The
      International Prostate Symptom Score (I-PSS) was also associated, but apparently
      to a lesser extent, with the timing of the invasive therapy. Finally, the overall
      severity evaluated using all of the above three indices, I-PSS, QOL index, and
      Qmax, in accordance with the 'Severity Criteria for BPH' issued by the Japanese
      Urological Association, was found to be a good measure for predicting the
      prognosis of patients with BPH treated with tamsulosin.

PMID- 16563135
TI  - Is chronic inflammatory change in the prostate the major cause of rising serum
      prostate-specific antigen in patients with clinical suspicion of prostate cancer?
AB  - AIM: To evaluate the cause of elevated prostate-specific antigen (PSA) in
      patients with transrectal needle biopsy negative for prostate cancer. METHODS:
      Serum PSA concentration, prostate volume, and pathologic findings were examined
      in 223 patients with negative biopsy for prostate cancer. The degree of prostate
      inflammation was determined by the extent and degree of inflammation shown by
      biopsy specimens and is expressed as an inflammation score (range: 0-36).
      RESULTS: A significant correlation was found between PSA concentration and
      prostate total volume (P=0.0001). Prostate chronic inflammation showed no
      correlation with PSA concentration (P=0.485, F=0.488). After allocating patients
      to normal PSA (<or=4 ng/mL) and high PSA (>4 ng/mL) groups, we found that serum
      PSA concentrations in both groups were predominantly affected by prostate total
      volume. CONCLUSIONS: An increase in prostate volume appears to be the major
      contributor to a high serum PSA concentration in patients with negative biopsy
      for prostate cancer. However, in contrast to previous reports, there was no
      correlation between the degree of prostate chronic inflammation and serum PSA
      concentrations.

PMID- 16563137
TI  - Placard-shaped in situ vaginal wall sling for the treatment of stress urinary
      incontinence.
AB  - PURPOSE: To evaluate the efficacy of a simple and economic procedure using a
      placard-shaped in situ anterior vaginal wall sling for the treatment of stress
      urinary incontinence, with or without cystocele repair. METHODS: From July 2003
      to July 2004, 14 female patients (mean age 45.21 years, range 37-57) were
      operated upon because of stress urinary incontinence (SUI) with the placard
      shaped in situ anterior vaginal wall sling technique. The average follow-up
      period was 11 months (range 4-14.5 months). Twelve patients were operated
      primarily with this technique and only two patients had undergone previous
      surgeries for the treatment of SUI (one patient had had two previous surgeries
      and the other had had one previous surgery). In all patients urethral
      hypermobility or/and bladder prolapse were observed. Filling cystometry showed
      sufficient bladder capacity with no detrusor overactivity. RESULTS: No urinary
      retention was observed in any patient in the postoperative period. While 11
      patients have 100% cure of incontinence, three patients started leakage of urine
      after 1-2 months after the operation (one patient had been operated upon twice
      before (and who was diabetic and obese) and two patients were primarily repaired
      by our technique). In two patients, suprapubic tenderness and redness were
      observed, and were treated by oral antibiotic and anti-inflammatory drugs.
      CONCLUSION: The placard technique is simple, cost-effective and has low incidence
      of urinary retention in the post-operative period. The success rate seems to be
      satisfactory and it can be applicable to patients who are primary cases of SUI
      with average body mass index. Yet longer term follow up and larger number of
      patients are needed before final conclusion can be drawn.

PMID- 16563138
TI  - Prenatal testicular torsion: ultrasonographic features, management and
      histopathological findings.
AB  - AIM: To highlight the ultrasonographic features of prenatal torsion of the testis
      in utero (IUTT) at presentation, the neonatal management and the histological
      findings postorchiectomy or biopsy. METHODS: Seven newborns underwent emergency
      exploration for IUTT. All patients underwent a sonography and real-time color
      Doppler ultrasound study of the scrotum before any surgical procedure. A
      histological examination was performed in the removed specimens. RESULTS:
      Sonography of the scrotum revealed enlarged, heterogeneous testes. In all cases
      the color and power Doppler did not reveal any flow signal on the affected side.
      Four newborn with unilateral testicular torsion underwent orchiectomy and
      contralateral orchidopexy. In one neonate after detorsion and with the absence of
      gangrenous changes and a reassuring biopsy, a twisted testis could be treated
      conservatively with orchidopexy. In another case, the parents, acknowledging the
      inviability of the affected testis, gave consent only for a biopsy of the testis.
      In the neonate with bilateral IUTT, bilateral testicular biopsies were performed.
      Histology of the removed testes variably showed interstitial red cell extravasion
      and coagulation or hemorrhagic necrosis. Light microscopy of the preserved testis
      highlighted surviving seminiferous tubules, with gonocytes, spermatogonia and
      fetal Sertoli cells. CONCLUSIONS: An early diagnosis and treatment in IUTT is
      essential. Surgical exploration should be always performed through the inguinal
      route. In bilateral IUTT testes should be left to try to assure, as long as
      possible, a residual Leydig cell function.

PMID- 16563139
TI  - Cytokeratin-20 and seminal vesicle secretory protein VI as possible marker
      proteins in urinary bladder preneoplastic lesions induced by N-butyl-N-(4
      hydroxybutyl) nitrosamine.
AB  - BACKGROUND: A simple and non-invasive methods for the diagnosis of transitional
      cell carcinoma of the bladder are needed for the prevention of invasive tumor. A
      proteomic technology has recently been developed to facilitate protein profiling
      of biological mixtures. We tried to detect the marker proteins by proteomic
      approach during the initiation stages on N-butyl-N-(4-hydroxybutyl) nitrosamine
      (BBN)-induced bladder carcinogenesis in rats. METHODS: Ten rats in group A were
      given 0.05% BBN in drinking water for 12 weeks. Other 10 rats in group B with 10
      rats were designated as a control group and were not given BBN. Whole urinary
      bladders of all rats were excised at 12 weeks from the beginning of the
      experiment. Conventional proteomics was performed with high resolution 2
      dimension gel electrophoresis followed by computational image analysis and
      protein identification using mass spectrometry. RESULTS: A comparison of urinary
      bladder hyperplasia tissue with control tissue showed that five proteins; actin
      gamma2 propeptide, cytokeratin-20 (CK-20), proapolipoprotein, alpha2 actin (alpha
      cardiac actin) and heat shock 27 kDa protein-1 were over-expressed in
      hyperplastic tissues. Three proteins; transcription factor myocardin, seminal
      vesicle secretory protein VI (SVS-VI) precursor and hypothetical protein RMT-7
      were under-expressed in hyperplastic tissues. CONCLUSION: In our animal mode, BBN
      induced urinary bladder mucosal hyperplasia resulted in an increase in the
      expression of five proteins and a decrease in the expression of three proteins.
      Of these, CK-20 and SVS-VI seem to be of particular interest. However other
      method such as Western blotting seems to be needed for confirmation of these
      proteins and more information on human bladder tissue is needed for clinical
      application.

PMID- 16563140
TI  - Importance of C16 ceramide accumulation during apoptosis in prostate cancer
      cells.
AB  - AIM: Adenocarcinoma of the prostate is one of the most frequently diagnosed non
      cutaneous cancers and the second leading cause of cancer-related deaths among men
      in the United States. To fully understand the role of ceramide during apoptosis
      induced by androgen ablation, we modified the levels of intracellular ceramide by
      pharmacological agents as well as through serum deprivation in androgen-dependent
      and independent cell lines. METHODS: Ceramide levels were modified using N
      oleoylethanolamine (NOE), sphingosine-1-phosphate (S1P) as well as through serum
      deprivation, in LNCaP, DU145 and PC-3 prostate cancer cells. Various methods
      including nonyl acridine orange staining, propidium iodide staining/cell cycle
      analysis and lipid analysis were utilized. RESULTS: Our results demonstrate that
      the inhibition of acid ceramidase by NOE enhances the intracellular ceramide
      levels induced by androgen ablation in androgen-dependent LNCaP cells, and is
      accompanied by an increase in apoptotic cells. Sphingosine 1-phosphate had no
      effect in rescuing LNCaP cells from apoptosis induced by androgen ablation. Our
      results also show that serum deprivation causes intracellular ceramide
      accumulation and apoptosis in androgen-independent prostate cancer cells.
      CONCLUSIONS: Our studies indicate that the increase in intracellular ceramide
      itself, but not the balance between ceramide and S1P, determines whether LNCaP
      cells undergo apoptosis. Our results also show that the increase in intracellular
      ceramide strongly correlates with apoptosis induced by serum deprivation even in
      androgen-independent prostate cancer cell lines.

PMID- 16563141
TI  - HtrA2 is up-regulated in the rat testis after experimental cryptorchidism.
AB  - AIM: The aim of the present study was to elucidate the role of high temperature
      requirement A2 (HtrA2) in germ cell loss in the heat-stressed testis. METHODS: We
      examined the expression of HtrA2, caspase-9 activity and proteolytic activity of
      HtrA2 in the rat testis, and their in vivo responses to experimental cryptorchid
      treatment. RESULTS: Northern analysis revealed the expression of HtrA2 mRNA
      peaked at days 1 and 7 after cryptorchid treatment. While expression of HtrA2
      mRNA was seen in the spermatogonium, spermatocytes and some spermatids in normal
      adult rat testis, experimental cryptorchidism treatment resulted in a marked
      increase in its signal intensity in spermatocytes and some spermatids, and the
      layers of spermatogonium and early primary spermatocytes became negative at days
      1 and 7 after the treatment. However, the spermatogonium, Sertoli cells and
      interstitial cells appeared to have strong intensities at days 14, 28 and 56
      after the treatment. Western analysis revealed the expression of HtrA2 protein
      peaked at day 2 coinciding with the increase of positive spermatogonium, the
      appearance of protein-positive interstitial cells, and day 28 coinciding with the
      reappearance of protein-positive interstitial cells. Caspase-9 activity peaked at
      day 2 and HtrA2 proteolytic activity peaked at day 28. Consequently, the first
      peak of HtrA2 mRNA expression was followed by the peak of caspase-9 activity and
      the second peak was followed by the peak of proteolytic activity; however, the
      second peak of mRNA expression had considerable chronological difference from
      that of the protein. CONCLUSION: These findings suggest the probabilities that
      the heat stress results in germ cell death by a caspase-independent manner with
      the elevation of HtrA2 proteolytic activity, as well as a caspase-dependent
      manner with the elevation of caspase-9 activity.

PMID- 16563142
TI  - Laparoscopic removal of a retroperitoneal extralobar pulmonary sequestration in
      an adult.
AB  - A 41-year-old male patient presented with dull left flank pain. A computed
      tomography (CT) showed a subdiaphragmatic retroperitoneal extra-adrenal mass. A
      magnetic resonance image demonstrated it was hypointense on T1 weighted and
      hyperintense on T2. Serum analyses for adrenal hormones revealed no abnormality.
      [I131]metaiodo-benzylguanidene scintigraphy showed no abnormal uptake. The
      patient underwent laparoscopic removal to manage the symptoms and to make a
      pathological diagnosis, which was an extralobar pulmonary sequestration. Another
      congenital lung malformation was not detected on chest CT scan. The symptom was
      relieved postoperatively.

PMID- 16563144
TI  - Hand-assisted laparoscopic radical nephrectomy using intraoperative
      ultrasonography for left renal cell carcinoma involving a level I renal vein
      tumor thrombus.
AB  - This report concerns two male patients, 65 (case 1) and 72 (case 2) years old,
      with a left renal tumor involving a level I renal vein tumor thrombus, who
      underwent hand-assisted laparoscopic radical nephrectomy using intraoperative
      ultrasonography. With the patient in the flank position, a midline supraumbilical
      hand port and two other ports were placed. Intraoperative ultrasonography
      identified the extent of the tumor thrombus. After hilar control, complete
      resection with intact removal was performed. Surgery lasted 305 min for case 1
      and 237 min for case 2, with respective estimated blood loss of 410 mL and 572
      mL. No postoperative complications occurred. Pathological examination showed a
      clear cell carcinoma with a level I tumor thrombus and negative surgical margins.
      Because the ultrasound probe can be easily inserted and the specimen can be
      extracted safely and intact, hand-assisted laparoscopic radical nephrectomy is
      practicable and effective for left renal cell carcinoma involving a level I renal
      vein tumor thrombus.

PMID- 16563143
TI  - Thrombolytic therapy for traumatic unilateral renal artery thrombosis.
AB  - We report a case of traumatic unilateral renal artery thrombosis that was
      successfully treated by thrombolytic therapy. The patient was a 17-year-old
      woman, who had put her left upper abdomen between a wall and the handle of a
      ground roller when using it. A computed tomography scan with intravenous contrast
      showed a lack of contrast in the left kidney. Angiography showed complete
      occlusion of the left renal artery, and the diagnosis was traumatic left renal
      artery thrombosis. Following angiography, thrombolytic therapy was performed.
      Urokinase was administered into the left renal artery, and 360,000 units per 1.5
      h was required. Thrombus disappeared and flow of left renal artery was observed.
      Recovery of left renal function was seen on renoscintigraphy. Surgical maneuvers
      for traumatic renal artery thrombosis are autotransplantation or thrombectomy
      generally, but we think that thrombolytic therapy following angiography is a less
      invasive method and saves warm ischemic time.

PMID- 16563146
TI  - Angiomyofibroblastoma-like tumors (cellular angiofibroma).
AB  - Angiomyofibroblastoma-like tumor (cellular angiofibroma) is a rare,
      circumscribed, slow-growing mesenchymal tumor that occurs predominantly in the
      vulva, perineum, and pelvis of women. We report two cases of this tumor in men
      arising as paratesticular masses of the scrotum, summarize the history of this
      tumor, and discuss why efforts should be made to differentiate it from aggressive
      angiomyxoma. Recommended treatment is complete surgical excision with long-term
      follow up exams, as local recurrence may occur many years after resection of the
      lesion.

PMID- 16563145
TI  - Nephrectomy for benign disease? A case of isolated renal echinococcosis.
AB  - Cystic hydatid disease may be found in virtually any organ, although involvement
      of the urinary tract is relatively uncommon. We report a case of isolated renal
      hydatid disease presenting with hydatiduria. A short review of the literature
      regarding diagnosis and management of renal echinococcosis is also presented.

PMID- 16563147
TI  - Retroperitoneal extragonadal germ cell tumor presenting as a bulky pelvic mass of
      the obturator fossa.
AB  - Extragonadal germ cell tumors (EGGCT) are commonly found in the midline of the
      body. We report a rare case of a retroperitoneal EGGCT presenting as a bulky
      pelvic mass located between the left internal and external iliac arteries in a 29
      year-old man. His alpha-fetoprotein level was 12946.2 ng/mL and the biopsy of the
      tumor revealed a nonseminomatous germ cell tumor. After three cycles of
      chemotherapy (bleomycin/etoposide/cisplatin) followed by resection of all
      residual tumors, one cycle of salvage chemotherapy
      (etoposide/ifosphamide/cisplatin) was added. The patient was disease free at 21
      month follow up.

PMID- 16563148
TI  - Epididymo-orchitis caused by intravesically instillated bacillus Calmette-Guerin:
      genetically proven using a multiplex polymerase chain reaction method.
AB  - The intravesical instillation of bacillus Calmette-Guerin (BCG) is a standard
      therapy for superficial bladder carcinoma. Tuberculosis-like inflammation in the
      genitourinary tract is a serious complication of BCG. It can occur after a long
      interval from the cessation of the intravesical BCG therapy. If inflammation
      occurs, it is necessary to test whether the BCG strain has caused it or another
      mycobacterium species has. However, there has never been a report that proves BCG
      causes the inflammation, because BCG is difficult to differentiate from other
      strains of Mycobacterium bovis and other members of the Mycobacterium
      tuberculosis complex by conventional tests, including regular polymerase chain
      reaction (PCR). We first present a case of epididymo-orchitis, which developed 31
      months after the cessation of BCG therapy, detected using a multiplex PCR method
      as having been caused by BCG. Our report illustrates the efficacy of this method
      to detect the responsible microbe that is thought to be transmitted from the
      instillated BCG strain.

PMID- 16563149
TI  - Xanthogranulomatous orchitis in an adult Nigerian.
AB  - Xanthogranulomatous orchitis (XGO) is a rare benign disease of the testis which
      has not been previously documented in tropical Africa. We report a case of a 24
      year-old Nigerian man who presented with a painless left hemiscrotal swelling.
      Our clinical diagnosis was left testicular cancer. Testicular tumor markers were
      normal. At surgical exploration, we found a left testicular tumor.
      Histopathological examination of the specimen showed XGO of the left testis. He
      had left radical orchiectomy and left inguinal node dissection. He has remained
      stable 8 months after the treatment. Xanthogranulomatous orchitis cannot be
      distinguished clinically from testicular cancer unless by histopathological
      examination. Orchiectomy is the treatment of choice. However, in all patients and
      particularly young patients and those with a single testis, histopathological
      confirmation is suggested to avoid unnecessary radical orchiectomy, useless
      irradiation and ill-timed chemotherapy.

PMID- 16563150
TI  - Severe penile edema: an unusual presentation of metastatic Crohn disease.
AB  - A case of Crohn disease involving the penis is described. Diagnosis of a
      metastatic Crohn disease was suggested by penile biopsy. The patient was treated
      with prednisolone and azathioprine.

PMID- 16563151
TI  - Facilitating the technique of laparoscopic running urethrovesical anastomosis
      using Lapra-ty absorbable suture clips.
AB  - We herein describe a simplified technique for performing laparoscopic running
      urethrovesical anastomosis using Lapra-ty absorbable suture clips (Ethicon,
      Somerville, NJ, USA) during a laparoscopic radical prostatectomy (LRP). Using two
      20 cm absorbable sutures tied together and locked with Lapra-ty at their tail
      ends, the initiating mattress sutures are placed in the 5:30-6:30-o'clock area
      between the urethra and the bladder neck. The left and right running sutures are
      then made clockwise from the 6:30-12-o'clock position and counterclockwise from
      the 5:30-12-o'clock position, respectively. Both sutures are locked with proper
      tension by Lapra-ty at the 3, 9 and 12-o'clock positions, and then they are
      intracorporeally tied together just at the 12-o'clock position. In the initial 20
      cases, this anastomosis took 22.5 min on average to perform. We experienced no
      major urine extravasation and no anastomotic stricture to date.

PMID- 16563153
TI  - Screening of pesticide residues in soil and water samples from agricultural
      settings.
AB  - BACKGROUND: The role of agricultural practices in the selection of insecticide
      resistance in malaria vectors has so far been hypothesized without clear
      evidence. Many mosquito species, Anopheles gambiae in particular, lay their eggs
      in breeding sites located around agricultural settings. There is a probability
      that, as a result of farming activities, insecticide residues may be found in
      soil and water, where they exercise a selection pressure on the larval stage of
      various populations of mosquitoes. To confirm this hypothesis, a study was
      conducted in the Republic of Benin to assess the environmental hazards which can
      be generated from massive use of pesticides in agricultural settings. METHODS:
      Lacking an HPLC machine for direct quantification of insecticide residues in
      samples, this investigation was performed using indirect bioassays focussed on
      the study of factors inhibiting the normal growth of mosquito larvae in breeding
      sites. The speed of development was monitored as well as the yield of rearing An.
      gambiae larvae in breeding sites reconstituted with water and soil samples
      collected in agricultural areas known to be under pesticide pressure. Two strains
      of An. gambiae were used in this indirect bioassay: the pyrethroid-susceptible
      Kisumu strain and the resistant Ladji strain. The key approach in this
      methodology is based on comparison of the growth of larvae in test and in control
      breeding sites, the test samples having been collected from two vegetable farms.
      RESULTS: Results obtained clearly show the presence of inhibiting factors on test
      samples. A normal growth of larvae was observed in control samples. In breeding
      sites simulated by using a few grams of soil samples from the two vegetable farms
      under constant insecticide treatments (test samples), a poor hatching rate of
      Anopheles eggs coupled with a retarded growth of larvae and a low yield of adult
      mosquitoes from hatched eggs, was noticed. CONCLUSION: Toxic factors inhibiting
      the hatching of anopheles eggs and the growth of larvae are probably pesticide
      residues from agricultural practices. Samples used during this indirect assay
      have been stored in the laboratory and will be analysed with HPLC techniques to
      confirm hypothesis of this study and to identify the various end products found
      in soil and water samples from agricultural settings under pesticide pressure.

PMID- 16563154
TI  - Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development
      in BRCA1 mutation carriers.
AB  - BACKGROUND: The MDM2 gene encodes a negative regulator of the p53 tumour
      suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter
      (a T to G exchange at nucleotide 309) has been reported to produce accelerated
      tumour formation in individuals with inherited p53 mutations. We have
      investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of
      patients with germline mutations of BRCA1. METHODS: Genomic DNA was obtained for
      102 healthy controls and 116 patients with established pathogenic mutations of
      BRCA1 and Pyrosequencing technologytrade mark was used to determine the genotype
      at the MDM2 SNP309 locus. RESULTS: The polymorphism was present in 52.9% of the
      controls (G/T in 37.3% and G/G in 15.6%) and 58.6% of the BRCA1 mutation carriers
      (47.4% G/T and 11.2% G/G). Incidence of malignancy in female BRCA1 carriers was
      not significantly higher in SNP309 carriers than in wildtype (T/T) individuals
      (72.7% vs. 75.6%, p = 1.00). Mean age of diagnosis of first breast cancer was
      41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the
      SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80). CONCLUSION:
      We found no evidence that the MDM2 SNP309 accelerates tumour development in
      carriers of known pathogenic germline mutations of BRCA1.

PMID- 16563155
TI  - Anxiety and stress in the postpartum: is there more to postnatal distress than
      depression?
AB  - BACKGROUND: Postnatal depression has received considerable research and clinical
      attention, however anxiety and stress in the postpartum has been relatively
      ignored. Along with the widespread use of the Edinburgh Postnatal Depression
      Scale (EPDS), depression has become the marker for postnatal maladjustment.
      Symptoms of anxiety tend to be subsumed within diagnoses of depression, which can
      result in anxiety being minimized or overlooked in the absence of depression.
      Some researchers have identified the need to distinguish between postnatal
      depression and anxiety, and to discern cases where depression and anxiety co
      exist. The aim of this study was to assess the prevalence of postnatal distress
      using the EPDS and the Depression Anxiety Stress Scales (DASS-21). METHOD: As
      part of a larger cross-sectional study, the EPDS and DASS-21 were administered to
      a convenience sample of 325 primiparous mothers, who ranged in age from 18 to 44
      years (M = 32 years). Recruited through mother's groups and health centres in
      Melbourne Australia, inclusion was limited to mothers whose babies were aged
      between 6 weeks and 6 months. Analyses included comparisons between the
      classifications of women according to the EPDS and the DASS-21, and an
      exploration of the extent to which the EPDS identified anxious-depressed women.
      RESULTS: The EPDS identified 80 women (25%) as possibly depressed (using a cut
      off of over 9), of which the DASS-21 corroborated 58%. In the total sample, 61
      women (19%) were classified by the DASS-21 to be depressed. Using broader
      criteria for distress, it was revealed by the DASS-21 that a further 33 women
      (10%) showed symptoms of anxiety and stress without depression. A total of 41
      women (13%) had symptoms of anxiety either in isolation or in combination with
      depression. The DASS-21 identified 7% of the sample as being both anxious and
      depressed. This at-risk sub-group had higher mean EPDS and DASS-depression scores
      than their depressed-only counterparts. CONCLUSION: The prevalence of anxiety and
      stress in the present study points to the importance of assessing postnatal women
      for broader indicators of psychological morbidity than that of depression alone.
      The DASS-21 appears to be a useful instrument for this purpose.

PMID- 16563156
TI  - The impact of carotid plaque presence and morphology on mortality outcome in
      cardiological patients.
AB  - BACKGROUND: Carotid plaque severity and morphology can affect cardiovascular
      prognosis. We evaluate both the importance of echographically assessed carotid
      artery plaque geometry and morphology as predictors of death in hospitalised
      cardiological patients. METHODS: 541 hospitalised patients admitted in a
      cardiological division (age = 66 +/- 11 years, 411 men), have been studied
      through ultrasound Duplex carotid scan and successively followed-up for a median
      of 34 months. Echo evaluation assessed plaque severity and morphology (presence
      of heterogeneity and profile). RESULTS: 361 patients showed carotid stenosis (67%
      with < 50% stenosis, 18% with 50-69% stenosis, 9% with > 70% stenosis, 4% with
      near occlusion and 2% with total occlusion). During the follow-up period, there
      were 83 all-cause deaths (15% of the total population). Using Cox's proportional
      hazard model, age (RR 1.06, 95% CI 1.03-1.09, p = 0.000), ejection fraction > 50%
      (RR = 0.62, 95% CI 0.4-0.96, p = 0.03), treatment with statins (RR = 0.52, 95% CI
      0.29-0.95, p = 0.34) and the presence of a heterogeneous plaque (RR 1.6; 95% CI,
      1.2 to 2.14, p = 0.002) were independent predictors of death. Kaplan-Meier
      survival estimates have shown the best outcome in patients without plaque,
      intermediate in patients with homogeneous plaques and the worst outcome in
      patients with heterogeneous plaques (90% vs 79% vs 73%, p = 0.0001). CONCLUSION:
      In hospitalised cardiological patients, carotid plaque presence and morphology
      assessed by ultrasound are independent predictors of death.

PMID- 16563157
TI  - Onchocerca parasites and Wolbachia endosymbionts: evaluation of a spectrum of
      antibiotic types for activity against Onchocerca gutturosa in vitro.
AB  - BACKGROUND: The filarial parasites of major importance in humans contain the
      symbiotic bacterium Wolbachia and recent studies have shown that targeting of
      these bacteria with antibiotics results in a reduction in worm viability,
      development, embryogenesis, and survival. Doxycycline has been effective in human
      trials, but there is a need to develop drugs that can be given for shorter
      periods and to pregnant women and children. The World Health Organisation
      approved assay to screen for anti-filarial activity in vitro uses male Onchocerca
      gutturosa, with effects being determined by worm motility and viability as
      measured by reduction of MTT to MTT formazan. Here we have used this system to
      screen antibiotics for anti-filarial activity. In addition we have determined the
      contribution of Wolbachia depletion to the MTT reduction assay. METHODS: Adult
      male O. gutturosa were cultured on a monkey kidney cell (LLCMK 2) feeder layer in
      24-well plates with antibiotics and antibiotic combinations (6 to 10 worms per
      group). The macrofilaricide CGP 6140 (Amocarzine) was used as a positive control.
      Worm viability was assessed by two methods, (i) motility levels and (ii)
      MTT/formazan colorimetry. Worm motility was scored on a scale of 0 (immotile) to
      10 (maximum) every 5 days up to 40 days. On day 40 worm viability was evaluated
      by MTT/formazan colorimetry, and results were expressed as a mean percentage
      reduction compared with untreated control values at day 40. To determine the
      contribution of Wolbachia to the MTT assay, the MTT formazan formation of an
      insect cell-line (C6/36) with or without insect Wolbachia infection and treated
      or untreated with tetracycline was compared. RESULTS: Antibiotics with known anti
      Wolbachia activity were efficacious in this system. Rifampicin (5 x 10(-5) M) was
      the most effective anti-mycobacterial agent; clofazimine (1.25 x 10(-5) M and
      3.13 x 10(-6) M) produced a gradual reduction in motility and by 40 days had
      reduced worm viability. The other anti-mycobacterial drugs tested had limited or
      no activity. Doxycycline (5 x 10(-5) M) was filaricidal, but minocycline was more
      effective and at a lower concentration (5 x 10(-5) M and 1.25 x 10(-5) M).
      Inactive compounds included erythromycin, oxytetracycline, trimethoprim and
      sulphamethoxazole. The MTT assay on the insect cell-line showed that Wolbachia
      made a significant contribution to the metabolic activity within the cells, which
      could be reduced when they were exposed to tetracycline. CONCLUSION: The O.
      gutturosa adult male screen for anti-filarial drug activity is also valid for the
      screening of antibiotics for anti-Wolbachia activity. In agreement with previous
      findings, rifampicin and doxycycline were effective; however, the most active
      antibiotic was minocycline. Wolbachia contributed to the formation of MTT
      formazan in the MTT assay of viability and is therefore not exclusively a measure
      of worm viability and indicates that Wolbachia contributes directly to the
      metabolic activity of the nematode.

PMID- 16563158
TI  - Circum-Mediterranean cultural heritage and medicinal plant uses in traditional
      animal healthcare: a field survey in eight selected areas within the RUBIA
      project.
AB  - During the years 2003-2005, a comparative ethnobotanical field survey was
      conducted on remedies used in traditional animal healthcare in eight
      Mediterranean areas. The study sites were selected within the EU-funded RUBIA
      project, and were as follows: the upper Kelmend Province of Albania; the
      Capannori area in Eastern Tuscany and the Bagnocavallo area of Romagna, Italy;
      Cercle de Ouezanne, Morocco; Sierra de Aracena y Picos de Aroche Natural Park in
      the province of Huelva, Spain; the St. Catherine area of the Sinai Peninsula,
      Egypt; Eastern and Western Crete, Greece; the Paphos and Larnaca areas of Cyprus;
      and the Mitidja area of Algeria.One hundred and thirty-six veterinary
      preparations and 110 plant taxa were recorded in the survey, with Asteraceae and
      Lamiaceae being the most quoted botanical families. For certain plant species the
      survey uncovered veterinary phytotherapeutical indications that were very
      uncommon, and to our knowledge never recorded before. These include Anabasis
      articulata (Chenopodiaceae), Cardopatium corymbosum (Asteraceae), Lilium martagon
      (Liliaceae), Dorycnium rectum (Fabaceae), Oenanthe pimpinelloides (Apiaceae),
      Origanum floribundum (Lamiaceae), Tuberaria lignosa (Cistaceae), and Dittrichia
      graveolens (Asteraceae). These phytotherapeutical indications are briefly
      discussed in this report, taking into account modern phytopharmacology and
      phytochemistry.The percentage of overall botanical veterinary taxa recorded in
      all the study areas was extremely low (8%), however when all taxa belonging to
      the same botanical genus are considered, this portion increases to 17%.
      Nevertheless, very few plant uses were found to be part of a presumed
      "Mediterranean" cultural heritage in veterinary practices, which raises critical
      questions about the concept of Mediterraneanism in ethnobotany and suggests that
      further discussion is required.Nearly the half of the recorded veterinary plant
      uses for mammals uncovered in this survey have also been recorded in the same
      areas in human folk medicine, suggesting a strong link between human and
      veterinary medical practices, and perhaps also suggesting the adaptive origins of
      a few medical practices. Since most of the recorded data concern remedies for
      treating cattle, sheep, goats, and camels, it would be interesting to test a few
      of the recorded phytotherapeuticals in the future, to see if they are indeed able
      to improve animal healthcare in breeding environments, or to raise the quality of
      dairy and meat products in the absence of classical, industrial, veterinary
      pharmaceuticals.

PMID- 16563159
TI  - Recreational and occupational field exposure to freshwater cyanobacteria--a
      review of anecdotal and case reports, epidemiological studies and the challenges
      for epidemiologic assessment.
AB  - Cyanobacteria are common inhabitants of freshwater lakes and reservoirs
      throughout the world. Under favourable conditions, certain cyanobacteria can
      dominate the phytoplankton within a waterbody and form nuisance blooms. Case
      reports and anecdotal references dating from 1949 describe a range of illnesses
      associated with recreational exposure to cyanobacteria: hay fever-like symptoms,
      pruritic skin rashes and gastro-intestinal symptoms are most frequently reported.
      Some papers give convincing descriptions of allergic reactions while others
      describe more serious acute illnesses, with symptoms such as severe headache,
      pneumonia, fever, myalgia, vertigo and blistering in the mouth. A coroner in the
      United States found that a teenage boy died as a result of accidentally ingesting
      a neurotoxic cyanotoxin from a golf course pond. This death is the first recorded
      human fatality attributed to recreational exposure to cyanobacteria, although
      uncertainties surround the forensic identification of the suspected cyanotoxin in
      this case. We systematically reviewed the literature on recreational exposure to
      freshwater cyanobacteria. Epidemiological data are limited, with six studies
      conducted since 1990. Statistically significant increases in symptoms were
      reported in individuals exposed to cyanobacteria compared to unexposed
      counterparts in two Australian cohort studies, though minor morbidity appeared to
      be the main finding. The four other small studies (three from the UK, one
      Australian) did not report any significant association. However, the potential
      for serious injury or death remains, as freshwater cyanobacteria under bloom
      conditions are capable of producing potent toxins that cause specific and severe
      dysfunction to hepatic or central nervous systems. The exposure route for these
      toxins is oral, from ingestion of recreational water, and possibly by
      inhalation.A range of freshwater microbial agents may cause acute conditions that
      present with features that resemble illnesses attributed to contact with
      cyanobacteria and, conversely, acute illness resulting from exposure to
      cyanobacteria or cyanotoxins in recreational waters could be misdiagnosed.
      Accurately assessing exposure to cyanobacteria in recreational waters is
      difficult and unreliable at present, as specific biomarkers are unavailable.
      However, diagnosis of cyanobacteria-related illness should be considered for
      individuals presenting with acute illness following freshwater contact if a
      description is given of a waterbody visibly affected by planktonic mass
      development.

PMID- 16563161
TI  - Assessment of methods for amino acid matrix selection and their use on empirical
      data shows that ad hoc assumptions for choice of matrix are not justified.
AB  - BACKGROUND: In recent years, model based approaches such as maximum likelihood
      have become the methods of choice for constructing phylogenies. A number of
      authors have shown the importance of using adequate substitution models in order
      to produce accurate phylogenies. In the past, many empirical models of amino acid
      substitution have been derived using a variety of different methods and protein
      datasets. These matrices are normally used as surrogates, rather than deriving
      the maximum likelihood model from the dataset being examined. With few
      exceptions, selection between alternative matrices has been carried out in an ad
      hoc manner. RESULTS: We start by highlighting the potential dangers of
      arbitrarily choosing protein models by demonstrating an empirical example where a
      single alignment can produce two topologically different and strongly supported
      phylogenies using two different arbitrarily-chosen amino acid substitution
      models. We demonstrate that in simple simulations, statistical methods of model
      selection are indeed robust and likely to be useful for protein model selection.
      We have investigated patterns of amino acid substitution among homologous
      sequences from the three Domains of life and our results show that no single
      amino acid matrix is optimal for any of the datasets. Perhaps most interestingly,
      we demonstrate that for two large datasets derived from the proteobacteria and
      archaea, one of the most favored models in both datasets is a model that was
      originally derived from retroviral Pol proteins. CONCLUSION: This demonstrates
      that choosing protein models based on their source or method of construction may
      not be appropriate.

PMID- 16563162
TI  - Dominant negative retinoic acid receptor initiates tumor formation in mice.
AB  - BACKGROUND: Retinoic acid suppresses cell growth and promotes cell
      differentiation, and pharmacological retinoic acid receptor (RAR) activation is
      anti-tumorigenic. This begs the question of whether chronic physiological RAR
      activation by endogenous retinoids is likewise anti-tumorigenic. RESULTS: To
      address this question, we generated transgenic mice in which expression of a
      ligand binding defective dominant negative RARalpha (RARalphaG303E) was under the
      control of the mouse mammary tumor virus (MMTV) promoter. The transgene was
      expressed in the lymphoid compartment and in the mammary epithelium. Observation
      of aging mice revealed that transgenic mice, unlike their wild type littermates,
      developed B cell lymphomas at high penetrance, with a median latency of 40 weeks.
      MMTV-RARalphaG303E lymphomas were high grade Pax-5+, surface H+L Ig negative,
      CD69+ and BCL6- and cytologically and phenotypically resembled human adult high
      grade (Burkitt's or lymphoblastic) lymphomas. We postulated that mammary tumors
      might arise after a long latency period as seen in other transgenic models of
      breast cancer. We tested this idea by transplanting transgenic epithelium into
      the cleared fat pads of wild type hosts, thus bypassing lymphomagenesis. At 17
      months post-transplantation, a metastatic mammary adenocarcinoma developed in one
      of four transplanted glands whereas no tumors developed in sixteen of sixteen
      endogenous glands with wild type epithelium. CONCLUSION: These findings suggest
      that physiological RAR activity may normally suppress B lymphocyte and mammary
      epithelial cell growth and that global RAR inactivation is sufficient to initiate
      a stochastic process of tumor development requiring multiple transforming events.
      Our work makes available to the research community a new animal resource that
      should prove useful as an experimental model of aggressive sporadic lymphoma in
      immunologically uncompromised hosts. We anticipate that it may also prove useful
      as a model of breast cancer.

PMID- 16563163
TI  - Automatic pathway building in biological association networks.
AB  - BACKGROUND: Scientific literature is a source of the most reliable and
      comprehensive knowledge about molecular interaction networks. Formalization of
      this knowledge is necessary for computational analysis and is achieved by
      automatic fact extraction using various text-mining algorithms. Most of these
      techniques suffer from high false positive rates and redundancy of the extracted
      information. The extracted facts form a large network with no pathways defined.
      RESULTS: We describe the methodology for automatic curation of Biological
      Association Networks (BANs) derived by a natural language processing technology
      called Medscan. The curated data is used for automatic pathway reconstruction.
      The algorithm for the reconstruction of signaling pathways is also described and
      validated by comparison with manually curated pathways and tissue-specific gene
      expression profiles. CONCLUSION: Biological Association Networks extracted by
      MedScan technology contain sufficient information for constructing thousands of
      mammalian signaling pathways for multiple tissues. The automatically curated
      MedScan data is adequate for automatic generation of good quality signaling
      networks. The automatically generated Regulome pathways and manually curated
      pathways used for their validation are available free in the ResNetCore database
      from Ariadne Genomics, Inc. 1. The pathways can be viewed and analyzed through
      the use of a free demo version of PathwayStudio software. The Medscan technology
      is also available for evaluation using the free demo version of PathwayStudio
      software.

PMID- 16563160
TI  - Cyanobacterial lipopolysaccharides and human health - a review.
AB  - Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the
      cyanobacteria literature as toxins responsible for a variety of heath effects in
      humans, from skin rashes to gastrointestinal, respiratory and allergic reactions.
      The attribution of toxic properties to cyanobacterial LPS dates from the 1970s,
      when it was thought that lipid A, the toxic moiety of LPS, was structurally and
      functionally conserved across all Gram-negative bacteria. However, more recent
      research has shown that this is not the case, and lipid A structures are now
      known to be very different, expressing properties ranging from LPS agonists,
      through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is
      widely cited as a putative toxin, most of the small number of formal research
      reports describe cyanobacterial LPS as weakly toxic compared to LPS from the
      Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial
      LPS, and also examined the much lager body of literature relating to
      heterotrophic bacterial LPS and the atypical lipid A structures of some
      photosynthetic bacteria. While the literature on the biological activity of
      heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to
      review for the purposes of exclusion, we were unable to find a convincing body of
      evidence to suggest that heterotrophic bacterial LPS, in the absence of other
      virulence factors, is responsible for acute gastrointestinal, dermatological or
      allergic reactions via natural exposure routes in humans. There is a danger that
      initial speculation about cyanobacterial LPS may evolve into orthodoxy without
      basis in research findings. No cyanobacterial lipid A structures have been
      described and published to date, so a recommendation is made that
      cyanobacteriologists should not continue to attribute such a diverse range of
      clinical symptoms to cyanobacterial LPS without research confirmation.

PMID- 16563164
TI  - The Single Item Literacy Screener: evaluation of a brief instrument to identify
      limited reading ability.
AB  - BACKGROUND: Reading skills are important for accessing health information, using
      health care services, managing one's health and achieving desirable health
      outcomes. Our objective was to assess the diagnostic accuracy of the Single Item
      Literacy Screener (SILS) to identify limited reading ability, one component of
      health literacy, as measured by the S-TOFHLA. METHODS: Cross-sectional interview
      with 999 adults with diabetes residing in Vermont and bordering states.
      Participants were randomly recruited from Primary Care practices in the Vermont
      Diabetes Information System June 2003-December 2004. The main outcome was limited
      reading ability. The primary predictor was the SILS. RESULTS: Of the 999 persons
      screened, 169 (17%) had limited reading ability. The sensitivity of the SILS in
      detecting limited reading ability was 54% [95% CI: 47%, 61%] and the specificity
      was 83% [95% CI: 81%, 86%] with an area under the Receiver Operating
      Characteristics Curve (ROC) of 0.73 [95% CI: 0.69, 0.78]. Seven hundred seventy
      (77%) screened negative on the SILS and 692 of these subjects had adequate
      reading skills (negative predictive value = 0.90 [95% CI: 0.88, 0.92]). Of the
      229 who scored positive on the SILS, 92 had limited reading ability (positive
      predictive value = 0.4 [95% CI: 0.34, 0.47]). CONCLUSION: The SILS is a simple
      instrument designed to identify patients with limited reading ability who need
      help reading health-related materials. The SILS performs moderately well at
      ruling out limited reading ability in adults and allows providers to target
      additional assessment of health literacy skills to those most in need. Further
      study of the use of the SILS in clinical settings and with more diverse
      populations is warranted.

PMID- 16563165
TI  - Description of the methodology used in an ongoing pediatric care interventional
      study of children born with cleft lip and palate in South America [NCT00097149].
AB  - BACKGROUND: The contribution of birth defects, including cleft lip and palate, to
      neonatal and infant mortality and morbidity is substantial. As other mortality
      and morbidity causes including infections, hygiene, prematurity, and nutrition
      are eradicated in less developed countries, the burden of birth defects will
      increase proportionally. METHODS/DESIGN: We are using cleft lip and palate as a
      sentinel birth defect to evaluate its burden on neonatal and infant health and to
      assess the effectiveness of systematic pediatric care during the first month and
      first two years of life in decreasing this burden. The neonatal intervention,
      consisting of weekly pediatric evaluation and referral to appropriate care, is
      delivered to about 696 infants born with cleft lip and/or palate in 47 hospitals
      in South America. Neonatal mortality in this group will be compared to that in a
      retrospective control group of about 464 infants born with cleft lip and/or
      palate in the same hospitals. The subgroup of infants with isolated clefts of
      both the lip and palate (about 264) is also randomized into two groups,
      intervened and non-intervened, and further followed up over 2 years. Intervened
      cases are evaluated by pediatricians every three months and referred for
      appropriate care. The intervened and non-intervened cases will be compared over
      study outcomes to evaluate the intervention effectiveness. Non-intervened cases
      are matched and compared to healthy controls to assess the burden of cleft lip
      and palate. Outcomes include child's neurological and physical development and
      family social and economic conditions. DISCUSSION: Large-scale clinical trials to
      improve infant health in developing countries are commonly suggested, making it
      important to share the methods used in ongoing studies with other investigators
      implementing similar research. We describe here the content of our ongoing
      pediatric care study in South America. We hope that this may help researchers
      targeting this area to plan their studies more effectively and encourage the
      development of similar research efforts to target other birth defects or infant
      outcomes such as prematurity and low birth weight.

PMID- 16563167
TI  - Herpes encephalitis presenting as mild aphasia: case report.
AB  - BACKGROUND: Encephalitis presenting as a change in mental status can be
      challenging to recognize in the primary care setting. However, early detection
      via a low threshold of suspicion can be useful, leading in turn to early
      treatment and improved survival. CASE PRESENTATION: We present a case which we
      consider relevant to primary care practitioners. The patient in question
      presented with relatively mild mental status changes, progressing to confusion,
      dysnomia and delirium over a period of three days. While infection did not appear
      to be the leading cause on her differential diagnosis, she was found on extensive
      workup to have encephalitis caused by Herpes Simplex Virus type 1. CONCLUSION:
      The case is instructive for general practitioners and other clinicians to
      maintain vigilance for central nervous system (CNS) infections which may present
      atypically.

PMID- 16563166
TI  - A simplified explanation for the frameshift mutation that created a novel C
      terminal motif in the APETALA3 gene lineage.
AB  - BACKGROUND: The evolution of type II MADS box genes has been extensively studied
      in angiosperms. One of the best-understood subfamilies is that of the Arabidopsis
      gene APETALA3 (AP3). Previous work has demonstrated that the ancestral paleoAP3
      lineage was duplicated at some point within the basal eudicots to give rise to
      the paralogous TM6 and euAP3 lineages. This event was followed in euAP3 orthologs
      by the replacement of the C-terminal paleoAP3 motif with the derived euAP3 motif.
      It has been suggested that the new motif was created by an eight-nucleotide
      insertion that produced a translational frameshift. RESULTS: The addition of 25
      eudicot AP3 homologs to the existing dataset has allowed us to clarify the
      process by which the euAP3 motif evolved. Phylogenetic analysis indicates that
      the euAP3/TM6 duplication maps very close to the base of the core eudicots,
      associated with the families Trochodendraceae and Buxaceae. We demonstrate that
      although the transformation of paleoAP3 into euAP3 was due to a frameshift
      mutation, this was the result of a single nucleotide deletion. The use of
      ancestral character state reconstructions has allowed us to demonstrate that the
      frameshift was accompanied by few other nucleotide changes. We further confirm
      that the sequence is evolving as coding region. CONCLUSION: This study
      demonstrates that the simplest of genetic changes can result in the remodeling of
      protein sequence to produce a kind of molecular 'hopeful monster.' Moreover, such
      a novel protein motif can become conserved almost immediately on the basis of
      what appears to be a rapidly generated new function. Given that the existing data
      on the function of such C-terminal motifs are somewhat disparate and
      contradictory, we have sought to synthesize previous findings within the context
      of the current analysis and thereby highlight specific hypotheses that require
      further investigation before the significance of the euAP3 frameshift event can
      be fully understood.

PMID- 16563168
TI  - Bacterial repetitive extragenic palindromic sequences are DNA targets for
      Insertion Sequence elements.
AB  - BACKGROUND: Mobile elements are involved in genomic rearrangements and virulence
      acquisition, and hence, are important elements in bacterial genome evolution. The
      insertion of some specific Insertion Sequences had been associated with
      repetitive extragenic palindromic (REP) elements. Considering that there are a
      sufficient number of available genomes with described REPs, and exploiting the
      advantage of the traceability of transposition events in genomes, we decided to
      exhaustively analyze the relationship between REP sequences and mobile elements.
      RESULTS: This global multigenome study highlights the importance of repetitive
      extragenic palindromic elements as target sequences for transposases. The study
      is based on the analysis of the DNA regions surrounding the 981 instances of
      Insertion Sequence elements with respect to the positioning of REP sequences in
      the 19 available annotated microbial genomes corresponding to species of bacteria
      with reported REP sequences. This analysis has allowed the detection of the
      specific insertion into REP sequences for ISPsy8 in Pseudomonas syringae DC3000,
      ISPa11 in P. aeruginosa PA01, ISPpu9 and ISPpu10 in P. putida KT2440, and ISRm22
      and ISRm19 in Sinorhizobium meliloti 1021 genome. Preference for insertion in
      extragenic spaces with REP sequences has also been detected for ISPsy7 in P.
      syringae DC3000, ISRm5 in S. meliloti and ISNm1106 in Neisseria meningitidis MC58
      and Z2491 genomes. Probably, the association with REP elements that we have
      detected analyzing genomes is only the tip of the iceberg, and this association
      could be even more frequent in natural isolates. CONCLUSION: Our findings
      characterize REP elements as hot spots for transposition and reinforce the
      relationship between REP sequences and genomic plasticity mediated by mobile
      elements. In addition, this study defines a subset of REP-recognizer transposases
      with high target selectivity that can be useful in the development of new tools
      for genome manipulation.

PMID- 16563169
TI  - Expression profiles of cIRF6, cLHX6 and cLHX7 in the facial primordia suggest
      specific roles during primary palatogenesis.
AB  - BACKGROUND: The LIM-homeodomain transcription factors LHX7 and LHX6 have been
      implicated in palatogenesis in mice and thus may also contribute to the incidence
      of isolated palatal clefts and/or clefts of the lip and primary palate (CL/P) in
      humans. Causative mutations in the transcription factor IRF6 have also been
      identified in two allelic CL/P syndromes and common polymorphisms in the same
      gene are significantly associated with non-syndromal CL/P in different
      populations. RESULTS: Here we report the isolation of chick orthologues of LHX7,
      LHX6 and IRF6 and the first characterisation of their profiles of expression
      during morphogenesis of the midface with emphasis on the period around formation
      of the primary palate. LHX7 and LHX6 expression was restricted to the
      ectomesenchyme immediately underlying the ectoderm of the maxillary and
      mandibular primordia as well as to the lateral globular projections of the medial
      nasal process, again underlying the pre-fusion primary palatal epithelia. In
      contrast, IRF6 expression was restricted to surface epithelia, with elevated
      levels around the frontonasal process, the maxillary primordia, and the nasal
      pits. Elsewhere, high expression was also evident in the egg tooth primordium and
      in the apical ectodermal ridge of the developing limbs. CONCLUSION: The
      restricted expression of both LHX genes and IRF6 in the facial primordia suggests
      roles for these gene products in promoting directed outgrowth and fusion of the
      primary palate. The manipulability, minimal cost and susceptibility of chicks to
      CL/P will enable more detailed investigations into how perturbations of IRF6,
      LHX6 and LHX7 contribute to common orofacial clefts.

PMID- 16563170
TI  - Comparison of the SF-6D and the EQ-5D in patients with coronary heart disease.
AB  - BACKGROUND: The SF-6D was derived from the SF-36. A single summary score is
      obtained allegedly preserving the descriptive richness and sensitivity to change
      of the SF-36 into utility measurement. We compared the SF-6D and EQ-5D on domain
      content, scoring distribution, pre-treatment and change scores. METHODS: The SF
      6D and the EQ-5D were completed prior to intervention and 1, 3, 6 and 12 months
      post-intervention in a study enrolling 561 patients with symptomatic coronary
      stenosis. Patients were randomized to off-pump coronary artery bypass surgery
      (CABG), standard on-pump CABG, or percutaneous transluminal coronary angioplasty
      (PTCA). Baseline and change over time scores were compared using parametric and
      non-parametric tests. RESULTS: The relative contribution of similar domains
      measuring daily functioning to the utility scores differed substantially. SF-6D
      focused more on social functioning, while EQ-5D gave more weight to physical
      functioning. Pain and mental health had similar contributions. The scoring range
      of the EQ-5D was twice the range of the SF-6D. Before treatment, EQ-5D and SF-6D
      mean scores appeared similar (0.64 versus 0.63, p = 0.09). Median scores,
      however, differed substantially (0.69 versus 0.60), a difference exceeding the
      minimal important difference of both instruments. Agreement was low, with an
      intra-class correlation of 0.45.Finally, we found large differences in measuring
      change over time. The SF-6D recorded greater intra-subject change in the PTCA
      group. Only the EQ-5D recorded significant change in the CABG-groups. In the
      latter groups changes in SF-6D domains cancelled each other out. CONCLUSION:
      Although both instruments appear to measure similar constructs, the EQ-5D and SF
      6D are quite different. The low agreement and the differences in median values,
      scoring range and sensitivity to change after intervention show that the EQ-5D
      and SF-6D yield incomparable scores in patients with coronary heart disease.

PMID- 16563171
TI  - Evaluation of a multifaceted "resident-as-teacher" educational intervention to
      improve morning report.
AB  - BACKGROUND: Resident-led morning report is an integral part of most residency
      programs and is ranked among the most valuable of educational experiences. The
      objectives of this study were to evaluate the effect of a resident-as-teacher
      educational intervention on the educational and teaching experience of morning
      report. METHODS: All senior internal medicine residents were invited to
      participate in this study as teaching participants. All internal medicine
      residents and clerks were invited to participate as audience participants. The
      educational intervention included reading material, a small group session and
      feedback after teaching sessions. The educational and teaching experiences were
      rated prior to and three months after the intervention using questionnaires.
      RESULTS: Forty-six audience participants and 18 teaching participants completed
      the questionnaires. The degree to which morning report met the educational needs
      of the audience was higher after the educational intervention (effect size, d =
      0.26, p = 0.01). The perceptions of the audience were that delivery had improved
      and that the sessions were less intimidating and more interactive. The perception
      of the teaching participants was that delivery was less stressful, but this group
      now reported greater difficulty in engaging the audience and less confidence in
      their medical knowledge. CONCLUSION: Following the educational intervention the
      audience's perception was that the educational experience had improved although
      there were mixed results for the teaching experience. When evaluating such
      interventions it is important to evaluate the impact on both the educational and
      teaching experiences as results may differ.

PMID- 16563172
TI  - Prognostic value of monitoring tumour markers CA 15-3 and CEA during fulvestrant
      treatment.
AB  - BACKGROUND: At many centres tumour markers are used to detect disease recurrence
      and to monitor response to therapy in patients with advanced disease, although
      the real value of serial observation of marker levels remains disputed. In this
      study, we evaluated the prognostic value of tumour markers for predicting
      response (partial response [PR], stable disease [SD] > or = 6 months), de novo
      disease progression (PD) and secondary PD in patients receiving fulvestrant
      ('Faslodex') 250 mg/month for the treatment of metastatic breast cancer (MBC).
      METHODS: Changes in cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen
      (CEA) were prospectively monitored (monthly) and were also evaluated for the 3
      months preceding secondary PD. Data from 67 patients with previously treated MBC
      participating in a Compassionate Use Programme were analysed. RESULTS: In
      patients with a PR (n = 7 [10.4%]), a non-significant increase in CA 15-3
      occurred during the first 6 months of treatment; CEA was significantly reduced (P
      = 0.0165). In patients with SD >/= 6 months (n = 28 [41.8%]), both CA 15-3 (P <
      0.0001) and CEA (P = 0.0399) levels increased significantly after 6 months
      treatment. In those experiencing de novo PD (n = 32 [47.8%]), CA 15-3 increased
      significantly (P < 0.0001) after 4 months; CEA also increased significantly (P =
      0.0002) during the same time period. Both CA 15-3 (P < 0.0001) and CEA (P <
      0.0001) increased significantly in the 3 months preceding secondary PD.
      CONCLUSION: CA 15-3 increases in patients progressing on fulvestrant but may also
      increase in those experiencing clinical benefit; this should not be taken as a
      sign of PD without verification. Overall, both CA 15-3 and CEA appear to be poor
      prognostic markers for determining progression in patients receiving fulvestrant.

PMID- 16563173
TI  - Life time suicidal thoughts in an urban community in Hanoi, Vietnam.
AB  - BACKGROUND: Suicidal thought is a risk factor and a stage in the suicidal process
      from planning to attempting and dying by suicide. To date, studies on suicidal
      thought in the general population, especially in Asian communities, have been
      limited. METHOD: The WHO SUPRE-MISS (the multisite intervention study on suicidal
      behaviours) community survey questionnaire was filled in for 2,280 randomly
      selected residents of the DongDa district of Hanoi, Vietnam by means of face-to
      face interviews. This multi-factor questionnaire includes such variables as
      sociodemographic information, suicidal thought and history of suicide attempts,
      physical health, alcohol consumption and medication. RESULTS: Prevalence rates
      for life time suicidal thoughts, suicide plans and suicide attempts were 8.9%,
      1.1% and 0.4% respectively. Suicidal thoughts are associated with multiple
      characteristics, such as female gender, single/widowed/separated/divorced marital
      status, low income, lifestyle (use of alcohol, sedatives and pain relief
      medication), but not with low education or employment status. Having no religion
      and being a Buddhist appear to be protective factors for suicidal thought. The
      ratio of suicidal thoughts, suicide plans and suicide attempts on a lifetime
      basis is 22.3:2.8:1. CONCLUSION: In Vietnam, as in Western and other Asian
      countries, suicidal thoughts are associated with similar negative psychosocial
      risk factors, lifestyle and emotional problems, which implies that suicide
      preventive measure developed elsewhere can be adjusted to Vietnamese condition.
      Understanding the unique and common risks in a culture may assist in prediction
      and control.

PMID- 16563174
TI  - A promoter haplotype of the interleukin-18 gene is associated with juvenile
      idiopathic arthritis in the Japanese population.
AB  - Recently, we reported that genetic polymorphisms within the human IL18 gene were
      associated with disease susceptibility to adult-onset Still's disease (AOSD),
      which is characterized by extraordinarily high serum levels of IL-18. Because
      high serum IL-18 induction has also been observed in the systemic type of
      juvenile idiopathic arthritis (JIA), we investigated whether similar genetic
      skewing is present in this disease. Three haplotypes, S01, S02, and S03, composed
      of 13 genetic polymorphisms covering two distinct promoter regions, were
      determined for 33 JIA patients, including 17 with systemic JIA, 10 with
      polyarthritis, and 6 with oligoarthritis. Haplotypes were also analyzed for 28
      AOSD patients, 164 rheumatoid arthritis (RA) patients, 102 patients with collagen
      diseases, and 173 healthy control subjects. The frequency of individuals carrying
      a diplotype configuration (a combination of two haplotypes) of S01/S01 was
      significantly higher in the JIA patients, including all subgroups, than in the
      healthy controls (P = 0.0045, Fischer exact probability test; odds ratio (OR) =
      3.55, 95% confidence interval (CI) = 1.55-8.14). In patients with systemic JIA,
      its frequency did not differ statistically from that of normal controls.
      Nevertheless, it is possible that haplotype S01 is associated with the phenotype
      of high IL-18 production in systemic JIA because the patients carrying S01/S01
      showed significantly higher serum IL-18 levels compared with patients with other
      diplotype configurations (P = 0.017, Mann-Whitney U test). We confirmed that the
      frequency of the diplotype configuration of S01/S01 was significantly higher in
      AOSD patients than in healthy control subjects (P = 0.011, OR = 3.45, 95% CI =
      1.42-8.36). Furthermore, the RA patients were also more predisposed to have
      S01/S01 (P = 0.018, OR = 2.00, 95% CI = 1.14-3.50) than the healthy control
      subjects, whereas the patients with collagen diseases did not. In summary, the
      diplotype configuration of S01/S01 was associated with susceptibility to JIA as
      well as AOSD and RA, and linked to significantly higher IL-18 production in
      systemic JIA. Possession of the diplotype configuration of S01/S01 would be one
      of the genetic risk factors for susceptibility to arthritis in the Japanese
      population.

PMID- 16563175
TI  - The matrix-forming phenotype of cultured human meniscus cells is enhanced after
      culture with fibroblast growth factor 2 and is further stimulated by hypoxia.
AB  - Human meniscus cells have a predominantly fibrogenic pattern of gene expression,
      but like chondrocytes they proliferate in monolayer culture and lose the
      expression of type II collagen. We have investigated the potential of human
      meniscus cells, which were expanded with or without fibroblast growth factor 2
      (FGF2), to produce matrix in three-dimensional cell aggregate cultures with a
      chondrogenic medium at low (5%) and normal (20%) oxygen tension. The presence of
      FGF2 during the expansion of meniscus cells enhanced the re-expression of type II
      collagen 200-fold in subsequent three-dimensional cell aggregate cultures. This
      was increased further (400-fold) by culture in 5% oxygen. Cell aggregates of FGF2
      expanded meniscus cells accumulated more proteoglycan (total glycosaminoglycan)
      over 14 days and deposited a collagen II-rich matrix. The gene expression of
      matrix-associated proteoglycans (biglycan and fibromodulin) was also increased by
      FGF2 and hypoxia. Meniscus cells after expansion in monolayer can therefore
      respond to chondrogenic signals, and this is enhanced by FGF2 during expansion
      and low oxygen tension during aggregate cultures.

PMID- 16563176
TI  - The dynamic proteome of Lyme disease Borrelia.
AB  - The proteome of the spirochete bacterium Borrelia burgdorferi, the tick-borne
      agent of Lyme disease, has been characterized by two different approaches using
      mass spectrometry, providing a launching point for future studies on the dramatic
      changes in protein expression that occur during transmission of the bacterium
      between ticks and mammals.

PMID- 16563177
TI  - Rapid molecular detection of methicillin-resistant Staphylococcus aureus: a cost
      effective tool for infection control in critical care?
AB  - Control strategies for methicillin-resistant Staphylococcus aureus (MRSA) in
      critical care remain debated. Timely detection of MRSA carriers is crucial to an
      effective isolation policy. In this issue, Harbarth and colleagues report rapid
      MRSA screening among intensive care unit-admitted patients using a PCR assay.
      Preemptive isolation for all admissions until screened negative for MRSA was
      associated with a reduction of intensive care unit-acquired MRSA infections in
      one of two study units. The data provide preliminary evidence to the
      effectiveness of a MRSA control strategy combining rapid screening by a molecular
      method and preventive isolation. Further controlled studies are needed to
      evaluate the cost-effectiveness of this intervention.

PMID- 16563178
TI  - The choice of catecholamines in septic shock: more and more good arguments to
      strengthen the known position, but don't lose the faith!
AB  - The choice of catecholamines for hemodynamic stabilisation in septic shock
      patients has been an ongoing debate for several years. Several studies have
      investigated the regional effects in septic patients. Because of an often very
      small sample size, because of inconsistent results and because of methodical
      problems in the monitoring techniques used in these studies, however, it is not
      possible to provide clear recommendations concerning the use of catecholamines in
      sepsis. Prospective and adequate-sized studies are necessary because outcome data
      are completely lacking.

PMID- 16563179
TI  - Breast asymmetry and predisposition to breast cancer.
AB  - INTRODUCTION: It has been shown in our previous work that breast asymmetry is
      related to several of the known risk factors for breast cancer, and that patients
      with diagnosed breast cancer have more breast volume asymmetry, as measured from
      mammograms, than age-matched healthy women. METHODS: In the present study, we
      compared the breast asymmetry of women who were free of breast disease at time of
      mammography, but who had subsequently developed breast cancer, with that of age
      matched healthy controls who had remained disease-free to time of the present
      study. The study group consisted of 252 asymptomatic women who had normal
      mammography, but went on to develop breast cancer. The control group were 252 age
      matched healthy controls whose mammograms were also normal and who remained free
      of cancer during the study period. Breast volume was calculated from the cranio
      caudal mammograms for each group, and the relationships between asymmetry,
      established risk factors and the presence or absence of breast cancer were
      explored. RESULTS: The group who went on to develop breast cancer had higher
      breast asymmetry than controls (absolute asymmetry odds ratio 1.50 per 100 ml,
      confidence interval (CI) 1.10, 2.04; relative asymmetry 1.09, CI 1.01, 1.18),
      increased incidence of family history of breast cancer, lower age at menarche,
      later menopause, later first pregnancies and a higher frequency of high risk
      breast parenchyma types. Conditional logistic regression analysis showed that
      breast asymmetry, height, family history of breast cancer, age at menarche,
      parenchyma type and menopausal status were significant independent predictors of
      breast cancer. When age at menopause was included in the model for the subgroup
      of post-menopausal women, absolute breast fluctuating asymmetry (FA) and relative
      breast FA remained significant effects. CONCLUSION: Breast asymmetry was greater
      in healthy women who later developed breast cancer than in women who did not.

PMID- 16563180
TI  - Spontaneous and therapeutic abortions and the risk of breast cancer among BRCA
      mutation carriers.
AB  - INTRODUCTION: BRCA1 and BRCA2 mutation carriers are at increased risk for
      developing both breast and ovarian cancer. It has been suggested that carriers of
      BRCA1/2 mutations may also be at increased risk of having recurrent (three or
      more) miscarriages. Several reproductive factors have been shown to influence the
      risk of breast cancer in mutation carriers, but the effects of spontaneous and
      therapeutic abortions on the risk of hereditary breast cancer risk have not been
      well studied to date. METHODS: In a matched case-control study, the frequencies
      of spontaneous abortions were compared among 1,878 BRCA1 mutation carriers, 950
      BRCA2 mutation carriers and 657 related non-carrier controls. The rates of
      spontaneous and therapeutic abortions were compared for carriers with and without
      breast cancer. RESULTS: There was no difference in the rate of spontaneous
      abortions between carriers of BRCA1 or BRCA2 mutations and non-carriers. The
      number of spontaneous abortions was not associated with breast cancer risk among
      BRCA1 or BRCA2 mutation carriers. However, BRCA2 carriers who had two or more
      therapeutic abortions faced a 64% decrease in the risk of breast cancer (odds
      ratio = 0.36; 95% confidence interval 0.16-0.83; p = 0.02). CONCLUSION: Carrying
      a BRCA1 or BRCA2 mutation is not a risk factor for spontaneous abortions and
      spontaneous abortions do not appear to influence the risk of breast cancer in
      carriers of BRCA1 or BRCA2 mutations. However, having two or more therapeutic
      abortions may be associated with a lowered risk of breast cancer among BRCA2
      carriers.

PMID- 16563181
TI  - Meningococcal disease: identifying high-risk cases.
AB  - In the previous issue of Critical Care, Vermont and colleagues presented a simple
      but well-executed observational study describing the levels of chemokines in the
      serum of 58 children with meningococcal sepsis. The chemokine levels correlated
      with disease severity and outcome. Significant correlations were demonstrated
      between admission chemokine levels and the Paediatric Risk of Mortality score,
      the Disseminated Intravascular Coagulopathy score, the Sequential Organ Failure
      Assessment score and laboratory parameters of disease severity. Additionally,
      nonsurvivors had much higher levels of chemokines compared with survivors, and
      the chemokine levels predicted mortality with a high degree of sensitivity and
      specificity. The findings are important as they indicate a possible mechanism for
      risk stratification in future trials of novel therapies in human sepsis, which as
      yet have not been successful.

PMID- 16563183
TI  - Usurped SLRPs: novel arthritis biomarkers exposed by catabolism of small leucine
      rich proteoglycans?
AB  - Proteolytic degradation of articular cartilage macromolecules, including the
      large aggregating cartilage proteoglycan (aggrecan) and small leucine-rich
      proteoglycans (SLRPs), is a prominent pathophysiological feature of arthritic
      diseases such as osteoarthritis (OA). Molecular profiling and monitoring of
      soluble/circulating proteoglycan catabolites that may be released from the
      cartilage matrix therefore represents an attractive strategy for evaluating OA
      disease progression and intervention. The recent identification of discrete
      metalloproteinase-sensitive SLRP cleavage sites, and complementary neoepitope
      bearing SLRP catabolites, extends decisive insight into the functional regulation
      of extracellular matrix integrity, and proffers poignant leads to assist in
      disclosing and appraising applicable biomarkers of cartilage degeneration during
      arthritis.

PMID- 16563182
TI  - Germline polymorphisms in SIPA1 are associated with metastasis and other
      indicators of poor prognosis in breast cancer.
AB  - INTRODUCTION: There is growing evidence that heritable genetic variation
      modulates metastatic efficiency. Our previous work using a mouse mammary tumor
      model has shown that metastatic efficiency is modulated by the GTPase-activating
      protein encoded by Sipa1 ('signal-induced proliferation-associated gene 1'). The
      aim of this study was to determine whether single nucleotide polymorphisms (SNPs)
      within the human SIPA1 gene are associated with metastasis and other disease
      characteristics in breast cancer. METHOD: The study population (n = 300)
      consisted of randomly selected non-Hispanic Caucasian breast cancer patients
      identified from a larger population-based series. Genomic DNA was extracted from
      peripheral leukocytes. Three previously described SNPs within SIPA1 (one within
      the promoter [-313G>A] and two exonic [545C>T and 2760G>A]) were characterized
      using SNP-specific PCR. RESULTS: The variant 2760G>A and the -313G>A allele were
      associated with lymph node involvement (P = 0.0062 and P = 0.0083, respectively),
      and the variant 545C>T was associated with estrogen receptor negative tumors (P =
      0.0012) and with progesterone negative tumors (P = 0.0339). Associations were
      identified between haplotypes defined by the three SNPs and disease progression.
      Haplotype 3 defined by variants -313G>A and 2760G>A was associated with positive
      lymph node involvement (P = 0.0051), and haplotype 4 defined by variant 545C>T
      was associated with estrogen receptor and progesterone receptor negative status
      (P = 0.0053 and P = 0.0199, respectively). CONCLUSION: Our findings imply that
      SIPA1 germline polymorphisms are associated with aggressive disease behavior in
      the cohort examined. If these results hold true in other populations, then
      knowledge of SIPA1 SNP genotypes could potentially enhance current staging
      protocols.

PMID- 16563184
TI  - Attributable mortality of Acinetobacter baumannii infections in critically ill
      patients: a systematic review of matched cohort and case-control studies.
AB  - INTRODUCTION: There has been a continuing controversy about whether infection
      with Acinetobacter baumannii increases morbidity and mortality independently of
      the effect of other confounding factors. METHODS: We performed a systematic
      review of matched case-control and cohort studies examining the mortality
      attributable to infection with or acquisition of A. baumannii (infection or
      colonization). We included in our review studies that compared mortality and/or
      morbidity of patients with acquisition of or infection with A. baumannii (cases)
      with the outcomes of matched patients without A. baumannii isolation from
      clinical specimens (controls). The relevant studies were identified from searches
      of the PubMed and the Cochrane Library databases. Two independent reviewers
      performed the literature search, study selection, and data extraction from nine
      identified relevant studies. RESULTS: The attributable mortalities, in the
      hospital and in the intensive care unit, of patients with A. baumannii infection
      in six matched case-control studies included in our review ranged from 7.8% to
      23% and from 10% to 43%, respectively. In addition, a statistically significantly
      higher mortality was reported for patients with A. baumannii acquisition; that
      is, colonization or infection (cases) compared with controls without such an
      acquisition in all four reviewed studies that reported data on this comparison.
      CONCLUSION: Although definitive statements about the mortality attributable to
      the acquisition of A. baumannii cannot be made from the available studies because
      of their methodological heterogeneity, the reviewed data suggest that infection
      with or acquisition of A. baumannii seems to be associated with increased
      mortality.

PMID- 16563185
TI  - A reanalysis of a published Affymetrix GeneChip control dataset.
AB  - A response to Preferred analysis methods for Affymetrix GeneChips revealed by a
      wholly defined control dataset by SE Choe, M Boutros, AM Michelson, GM Church and
      MS Halfon. Genome Biology 2005, 6:R16.

PMID- 16563188
TI  - Mining the genome and regulatory networks.

PMID- 16563187
TI  - Expression and function of inducible co-stimulator in patients with systemic
      lupus erythematosus: possible involvement in excessive interferon-gamma and anti
      double-stranded DNA antibody production.
AB  - Inducible co-stimulator (ICOS) is the third member of the CD28/cytotoxic T
      lymphocyte associated antigen-4 family and is involved in the proliferation and
      activation of T cells. A detailed functional analysis of ICOS on peripheral blood
      T cells from patients with systemic lupus erythematosus (SLE) has not yet been
      reported. In the present study we developed a fully human anti-human ICOS mAb
      (JTA009) with high avidity and investigated the immunopathological roles of ICOS
      in SLE. JTA009 exhibited higher avidity for ICOS than a previously reported mAb,
      namely SA12. Using JTA009, ICOS was detected in a substantial proportion of
      unstimulated peripheral blood T cells from both normal control individuals and
      patients with SLE. In CD4+CD45RO+ T cells from peripheral blood, the percentage
      of ICOS+ cells and mean fluorescence intensity with JTA009 were significantly
      higher in active SLE than in inactive SLE or in normal control individuals.
      JTA009 co-stimulated peripheral blood T cells in the presence of suboptimal
      concentrations of anti-CD3 mAb. Median values of [3H]thymidine incorporation were
      higher in SLE T cells with ICOS co-stimulation than in normal T cells, and the
      difference between inactive SLE patients and normal control individuals achieved
      statistical significance. ICOS co-stimulation significantly increased the
      production of IFN-gamma, IL-4 and IL-10 in both SLE and normal T cells. IFN-gamma
      in the culture supernatants of both active and inactive SLE T cells with ICOS co
      stimulation was significantly higher than in normal control T cells. Finally, SLE
      T cells with ICOS co-stimulation selectively and significantly enhanced the
      production of IgG anti-double-stranded DNA antibodies by autologous B cells.
      These findings suggest that ICOS is involved in abnormal T cell activation in
      SLE, and that blockade of the interaction between ICOS and its receptor may have
      therapeutic value in the treatment of this intractable disease.

PMID- 16563186
TI  - Phylogenetic and structural analysis of centromeric DNA and kinetochore proteins.
AB  - BACKGROUND: Kinetochores are large multi-protein structures that assemble on
      centromeric DNA (CEN DNA) and mediate the binding of chromosomes to microtubules.
      Comprising 125 base-pairs of CEN DNA and 70 or more protein components,
      Saccharomyces cerevisiae kinetochores are among the best understood. In contrast,
      most fungal, plant and animal cells assemble kinetochores on CENs that are longer
      and more complex, raising the question of whether kinetochore architecture has
      been conserved through evolution, despite considerable divergence in CEN
      sequence. RESULTS: Using computational approaches, ranging from sequence
      similarity searches to hidden Markov model-based modeling, we show that organisms
      with CENs resembling those in S. cerevisiae (point CENs) are very closely related
      and that all contain a set of 11 kinetochore proteins not found in organisms with
      complex CENs. Conversely, organisms with complex CENs (regional CENs) contain
      proteins seemingly absent from point-CEN organisms. However, at least three
      quarters of known kinetochore proteins are present in all fungi regardless of CEN
      organization. At least six of these proteins have previously unidentified human
      orthologs. When fungi and metazoa are compared, almost all have kinetochores
      constructed around Spc105 and three conserved multi-protein linker complexes
      (MIND, COMA, and the NDC80 complex). CONCLUSION: Our data suggest that critical
      structural features of kinetochores have been well conserved from yeast to man.
      Surprisingly, phylogenetic analysis reveals that human kinetochore proteins are
      as similar in sequence to their yeast counterparts as to presumptive Drosophila
      melanogaster or Caenorhabditis elegans orthologs. This finding is consistent with
      evidence that kinetochore proteins have evolved very rapidly relative to
      components of other complex cellular structures.

PMID- 16563190
TI  - Management of acute brain injury and associated respiratory issues.
AB  - Acute brain injury, in the form of trauma, stroke, or spontaneous hemorrhage,
      occurs commonly and in all age groups. Although the management of these
      conditions differs considerably, certain physiologic principles are shared by all
      and are useful in guiding the management of the most severely injured patients.
      This article reviews basic cerebral physiology and describes the links between
      physiology and management principles, emphasizing subjects relevant to the
      respiratory management of patients with acute brain injury.

PMID- 16563191
TI  - Diagnosis and management of pulmonary arterial hypertension: Implications for
      respiratory care.
AB  - Pulmonary arterial hypertension (PAH) is a pathological condition of the small
      pulmonary arteries. PAH is characterized histopathologically by vasoconstriction,
      vascular proliferation, in situ thrombosis, and remodeling of all 3 levels of the
      vascular walls. These pathologic changes result in progressive increases in the
      mean pulmonary-artery pressure and pulmonary vascular resistance, which, if
      untreated, leads to right-ventricular failure and death. PAH can be associated
      with multiple conditions or risk factors (eg, collagen vascular diseases, liver
      disease, human immunodeficiency virus, congenital heart disease, or ingestion of
      certain medications or toxins) or it can be idiopathic. Up to 10% of the
      idiopathic cases are familial. Regardless of the etiology, the clinical
      presentation, histopathologic lesions, and response to therapy are all similar.
      Early in the disease process, the signs and symptoms of PAH are often subtle and
      nonspecific, making diagnosis challenging. Patients most often present with
      progressively worsening dyspnea and fatigue. An extensive evaluation is indicated
      to diagnose PAH, decipher its etiology, and determine long-term treatment goals.
      Transthoracic echocardiogram is an excellent screening tool to evaluate PAH, but
      every patient requires a right-side heart catheterization to help stage the
      disease and guide therapy. Prior to a decade ago, clinicians were only able to
      offer symptomatic therapy to this challenging group of patients. Earlier
      diagnosis, rapidly advancing understanding of the pathogenesis, and an increasing
      number of treatment options have changed the course of PAH, which was once
      thought to be invariably fatal.

PMID- 16563192
TI  - The patient who has undergone lung transplantation: Implications for respiratory
      care.
AB  - Lung transplantation is now performed in patients with end-stage pulmonary
      parenchymal or vascular lung disease. The process of evaluating a patient for
      transplantation, managing the patient during the peri-operative period, and
      caring for the patient following transplantation is complex. Lung-transplant
      recipients are prone to unique complications of lung transplantation, as well as
      general complications of an immunosuppressed host. This article reviews the
      indications for, expected outcomes of, and management of complications that can
      develop following lung transplantation. Respiratory therapists play an
      instrumental role in assisting in the management of this group of patients in the
      pretransplant and post-transplant periods, and in their long-term management.

PMID- 16563189
TI  - IFNGR1 single nucleotide polymorphisms in rheumatoid arthritis.
AB  - On the basis of their biological function, potential genetic candidates for
      susceptibility to rheumatoid arthritis can be postulated. IFNGR1, encoding the
      ligand-binding chain of the receptor for interferon gamma, IFNgammaR1, is one
      such gene because interferon gamma is involved in the pathogenesis of the
      disease. In the coding sequence of IFNGR1, two nucleotide positions have been
      described to be polymorphic in the Japanese population. We therefore investigated
      the association of those two IFNGR1 single nucleotide polymorphisms with
      rheumatoid arthritis in a case-control study in a central European population.
      Surprisingly, however, neither position was polymorphic in the 364 individuals
      examined, indicating that IFNGR1 does not contribute to susceptibility to
      rheumatoid arthritis, at least in Caucasians.

PMID- 16563193
TI  - Diagnosis and management of idiopathic pulmonary fibrosis: Implications for
      respiratory care.
AB  - Although poorly understood, idiopathic pulmonary fibrosis is the most common of
      the idiopathic interstitial lung diseases. Its etiology is unknown, but how this
      fibrotic process develops in the lung has been studied over the last 60 years. It
      is a relatively rare disease, afflicting those 50-70 years of age, slightly more
      common among men than women, without racial predilection. The most common
      complaint is progressive shortness of breath. Pulmonary function testing reveals
      a restrictive ventilatory defect with a diminished diffusion capacity. The lungs
      demonstrate fibrotic and cystic areas interspersed with normal lung on
      radiographic and pathologic examination. No definitive medical treatment is
      available, although most patients are given trials of corticosteroids, alone or
      in combination with cytotoxic agents. On average, patients survive 2-4 years
      after diagnosis. Lung transplantation has been the only therapy shown to improve
      survival of those with idiopathic pulmonary fibrosis.

PMID- 16563194
TI  - Congestive heart failure: Diagnosis, pathophysiology, therapy, and implications
      for respiratory care.
AB  - Congestive heart failure (CHF) is a common clinical disorder that results in
      pulmonary vascular congestion and reduced cardiac output. CHF should be
      considered in the differential diagnosis of any adult patient who presents with
      dyspnea and/or respiratory failure. The diagnosis of heart failure is often
      determined by a careful history and physical examination and characteristic chest
      radiograph findings. The measurement of serum brain natriuretic peptide and
      echocardiography have substantially improved the accuracy of diagnosis. Therapy
      for CHF is directed at restoring normal cardiopulmonary physiology and reducing
      the hyperadrenergic state. The cornerstone of treatment is a combination of an
      angiotensin-converting-enzyme inhibitor and slow titration of a beta blocker.
      Patients with CHF are prone to pulmonary complications, including obstructive
      sleep apnea, pulmonary edema, and pleural effusions. Continuous positive airway
      pressure and noninvasive positive-pressure ventilation benefit patients in CHF
      exacerbations.

PMID- 16563195
TI  - Respiratory considerations in the patient with renal failure.
AB  - Lung and kidney function are intimately related in both health and disease.
      Respiratory changes help to mitigate the systemic effects of renal acid-base
      disturbances, and the reverse is also true, although renal compensation occurs
      more slowly than its respiratory counterpart. A large number of diseases affect
      both the lungs and the kidneys, presenting most often with alveolar hemorrhage
      and glomerulonephritis. Most of these conditions are uncommon or rare, although
      three of them--Wegener's granulomatosis, systemic lupus erythematosus, and
      Goodpasture's syndrome--are not infrequently encountered by respiratory care
      clinicians. Respiratory complications of chronic renal failure include pulmonary
      edema, fibrinous pleuritis, pulmonary calcification, and a predisposition to
      tuberculosis. Urinothorax is a rare entity associated with obstructive uropathy.
      Sleep disturbances are extremely common in patients with end-stage renal disease,
      with sleep apnea occurring in 60% or more of such patients. The management of
      patients with acute renal failure is frequently complicated by pulmonary edema
      and the effects of both fluid overload and metabolic acidosis. These processes
      affect the management of mechanical ventilation in such patients and may
      interfere with weaning. Successful lung-protective ventilation in patients with
      acute lung injury and renal failure may require modification of hemodialysis in
      order to combat severe acidemia. Hemodialysis-related hypoxemia, which was once
      believed to be the result of pulmonary leukostasis and complement activation, is
      explained by diffusion of CO2 into the dialysate, with concomitant alveolar
      hypoventilation in the process of maintaining a normal P(aCO2). Like acute lung
      injury, renal failure is a common complication of critical illness. An increasing
      body of evidence also supports the notion that the kidneys, like the lungs, are
      susceptible to injury induced as a result of positive-pressure mechanical
      ventilation.

PMID- 16563196
TI  - Myxoid liposarcoma metastatic to the thyroid gland: a case report and literature
      review.
AB  - We present the second reported case of a myxoid liposarcoma metastatic to the
      thyroid gland in a 51-year-old gentleman with previous liposarcoma of the right
      thigh. Myxoid liposarcoma has a relatively good prognosis but tends to recur
      locally. Metastases affecting the thyroid gland are a rare entity and most
      commonly arise from the kidney, lung or breast. Clinical presentation, patterns
      of recurrence and prognosis of myxoid liposarcoma and metastases to the thyroid
      gland are discussed.

PMID- 16563197
TI  - Concurrent chemoradiotherapy with carboplatin and uracil-ftegafur in patients
      with stage two (T2 N0 M0) squamous cell carcinoma of the glottic larynx.
AB  - This study aimed to evaluate the efficacy and toxicity of concurrent
      chemoradiotherapy as a primary treatment modality for larynx preservation in
      patients with stage two squamous cell carcinoma (SCC) of the glottic larynx.
      Between February 2000 and August 2003, a total of 20 patients received concurrent
      chemoradiotherapy. Carboplatin was given intravenously once a week during the
      period of radiotherapy. The weekly carboplatin dose was based on the area under
      the curve 1 to 1.25. Uracil-ftegafur (UFT) was given in a daily oral dose of 300
      mg as tegafur. Radiotherapy was delivered five days a week using a once-daily
      fractionation of 2.0 Gray (Gy), to a total dose of 66-72 Gy. The three-year
      overall survival rate with larynx preservation was 100 per cent. Concurrent
      chemoradiotherapy with carboplatin and UFT for stage two SCC of the glottic
      larynx was safe and effective in improving local control with larynx
      preservation.

PMID- 16563198
TI  - A comparative analysis of anterior versus posterior squamous cell carcinoma of
      the tongue: a 10-year review.
AB  - INTRODUCTION: The study sought to compare and contrast squamous cell carcinoma
      (SCC) of the anterior mobile tongue with SCC of the tongue base, with emphasis on
      clinical presentation, management and outcome. METHODS: This was a retrospective,
      comparative analysis of patients treated for SCC of the tongue over a 10-year
      period. Cox's regression model was used to assess the effect of tumour site on
      survival. RESULTS: The study included 142 patients, of whom 86 were treated for
      SCC of the anterior tongue and 56 for tongue base lesions. Patients with
      carcinoma of the anterior tongue tended to present with a visible lump or
      ulceration of the tongue, whereas the majority of patients with tongue base SCC
      presented with pain. Sixty per cent of anterior tongue lesions were early stage
      (I or II) at initial presentation as compared with 21 per cent of tongue base
      lesions. CONCLUSION: Patients with anterior tongue lesions had a better
      prognosis, but this was not statistically significant when adjusted for stage.

PMID- 16563199
TI  - Unpredicted transmission strategy of Gyrodactylus salaris (Monogenea:
      Gyrodactylidae): survival and infectivity of parasites on dead hosts.
AB  - The viviparous monogenean Gyrodactylus salaris continues to devastate Norwegian
      Atlantic salmon populations despite the extreme measures taken to control this
      pathogen. Increased understanding of parasite biology is needed to develop
      alternative control and management strategies of wild Atlantic salmon. We have
      examined temperature-dependent survival of G. salaris, both on and off the host.
      At 18 degrees C, survival off the host was 1 day, but at 3 degrees C parasites
      survived for 4 days. However, in contrast to assumptions made by earlier authors,
      many parasites remained with their host following its death. Ultrastructural
      evidence indicated that G. salaris individuals can feed on a dead host, and
      laboratory tests demonstrated that worms on their hosts more than double their
      life-span compared with individuals maintained off the host. Experimental
      infections also demonstrated that establishment and subsequent population growth
      of parasites previously maintained on dead hosts for 3 days, was similar to that
      of parasites transferred directly between living hosts. Hence, for G. salaris,
      dead infected hosts may increase the chances of successful transmission and be a
      potential important infection source in rivers and hatcheries.

PMID- 16563200
TI  - Molecular characterization of Thelastomatoidea (Nematoda: Oxyurida) from
      cockroaches in Australia.
AB  - A molecular approach was used to genetically characterize 5 species (Aoruroides
      queenslandensis, Blattophila sphaerolaima, Cordonicola gibsoni, Desmicola ornata
      and Leidynemella fusiformis) belonging to the superfamily Thelastomatoidea
      (Nematoda: Oxyurida), a group of pinworms that parasitizes terrestrial
      arthropods. The D3 domain of the large subunit of nuclear ribosomal RNA (LSU) was
      sequenced for individual specimens, and the analysis of the sequence data allowed
      the genetic relationships of the 5 species to be studied. The sequence variation
      in the D3 domain within individual species (0-1.8%) was significantly less than
      the differences among species (4.3-12.4%). Phylogenetic analyses, using maximum
      parsimony, maximum likelihood, and neighbour-joining, tree-building methods,
      established relationships among the 5 species of Thelastomatoidea and Oxyuris
      equi (a species of the order Oxyurida). The molecular approach employed provides
      the prospect for developing DNA tools for the specific identification of the
      Thelastomatoidea, irrespective of developmental stage and sex, as a basis for
      systematic, ecological and/or population genetic investigations of members within
      this superfamily.

PMID- 16563202
TI  - Antiparasitic activity of aromatic diamidines is related to apoptosis-like death
      in Trypanosoma cruzi.
AB  - Two aromatic diamidines, furamidine (DB75) and its phenyl-substituted analogue
      (DB569), which exhibit trypanocidal activity, were assayed against Trypanosoma
      cruzi and were found to induce apoptosis-like death characteristics such as
      nuclear DNA condensation and fragmentation, decreased mitochondrial membrane
      potential and phosphatidylserine exposure. DB569 displays superior trypanocidal
      activity compared to furamidine and also had higher ability to induce apoptosis
      like death in treated parasites. The present results showing apoptosis-like death
      in T. cruzi after treatment with both DB75 and DB569 make important contributions
      to the understanding of the mechanisms of the aromatic diamidines, which
      represent promising trypanocidal compounds.

PMID- 16563201
TI  - Three unrelated species, 3 sites, same host--monogenean parasites of the southern
      fiddler ray, Trygonorrhina fasciata, in South Australia: egg hatching strategies
      and larval behaviour.
AB  - The southern fiddler ray, Trygonorrhina fasciata (Rhinobatidae), is parasitized
      by 3 monogenean (platyhelminth) species from 3 families on 3 different sites of
      the host: Calicotyle australis (Monocotylidae) from the cloaca,
      Pseudoleptobothrium aptychotremae (Microbothriidae) from the skin and
      Branchotenthes octohamatus (Hexabothriidae) from the gills. Cues that promote egg
      hatching were investigated for each species and the behaviour of their larvae was
      also documented. Eggs were laid by parasites in vivo and maintained at 22 degrees
      C. Three different egg hatching and host finding strategies were discovered.
      Calicotyle australis eggs hatched spontaneously with a strong diurnal rhythm that
      is likely to be under circadian control. The larva is ciliated, photo-responsive
      and can survive for up to 24 h at 22 degrees C after hatching.
      Pseudoleptobothrium aptychotremae may have a 'bet-hedging' strategy. Some eggs
      hatched spontaneously and rhythmically. However, since the hatching success was
      low, it is possible that other eggs require a different cue provided by the host.
      The larva is also ciliated but shows no photo-response and was observed to remain
      active for <4 h at 22 degrees C after hatching. Branchotenthes octohamatus has a
      'sit-and-wait' strategy that depends on mechanical disturbance to stimulate
      hatching. The larva is unciliated, shows no photo-response but may survive for
      more than 2 days at 22 degrees C after hatching. The implications of hatching
      strategy, larval behaviour and morphology in the goal to find a host are
      discussed for each species.

PMID- 16563203
TI  - Quantitative PCR to detect, discriminate and quantify intracellular parasites in
      their host: an example from three microsporidians in Daphnia.
AB  - Reliable detection, discrimination and quantification of parasites are important
      for host-parasite studies and diagnostics. Microsporidial infections are
      problematic in this respect. Their discrimination and quantification using light
      microscopy is difficult because spores are the only light microscopically visible
      form of the parasite and they offer few distinct characters. We developed a
      quantitative PCR (qPCR) assay based on SYBR Green chemistry to quantify the
      microsporidia Glugoides intestinalis, Octosporea bayeri and Ordospora colligata
      in their host, the freshwater crustacean Daphnia magna. The assay allows the
      quantification of infection intensities in whole animals and is more than an
      order of magnitude more sensitive than light microscopy. Sampling and DNA
      extraction account for more than 90% of the residual variance in infection
      intensity data and this variance considerably impairs the resolution of qPCR.
      Where higher resolution is required, we propose using the ratio of parasite to
      host DNA as the measure of infection intensity. We show that this measure is
      robust and greatly improves resolution of qPCR. Additionally, this method can be
      applied to compare samples of unequal volume.

PMID- 16563204
TI  - The Brief Core Schema Scales (BCSS): psychometric properties and associations
      with paranoia and grandiosity in non-clinical and psychosis samples.
AB  - BACKGROUND: Traditional instruments that measure self-esteem may not relate
      directly to the schema construct as outlined in recent cognitive models. The
      Brief Core Schema Scales (BCSS) aim to provide a theoretically coherent self
      report assessment of schemata concerning self and others in psychosis. The scales
      assess four dimensions of self and other evaluation: negative-self, positive
      self, negative-other, positive-other. METHOD: We analysed the psychometric
      properties of the BCSS using a sample of 754 students recruited by email and 252
      people with psychosis recruited as part of a trial of cognitive therapy. We
      report the internal consistency, stability and the factor structure of the scale,
      and the association of the BCSS with measures of self-esteem and with symptoms of
      paranoia and grandiosity. RESULTS: The BCSS have good psychometric properties and
      have more independence from mood than the Rosenberg Self-Esteem Schedule. People
      with chronic psychosis reported extreme negative evaluations of both self and
      others on these scales, but their levels of self-esteem and positive evaluations
      of self and others were similar to the student sample. CONCLUSIONS: Extreme
      negative evaluations of self and others appear to be characteristic of the
      appraisals of people with chronic psychosis, and are associated with symptoms of
      grandiosity and paranoia in the non-clinical population. The BCSS may provide a
      more useful measure of schemata about self and others than traditional measures
      of self-esteem.

PMID- 16563205
TI  - Toward an alcohol use disorder continuum using item response theory: results from
      the National Epidemiologic Survey on Alcohol and Related Conditions.
AB  - BACKGROUND: Item response theory (IRT) was used to determine whether the DSM-IV
      diagnostic criteria for alcohol abuse and dependence are arrayed along a
      continuum of severity. METHOD: Data came from a large nationally representative
      sample of the US population, 18 years and older. A two-parameter logistic IRT
      model was used to determine the severity and discrimination of each DSM-IV
      criterion. Differential criterion functioning (DCF) was also assessed across
      subgroups of the population defined by sex, age and race-ethnicity. RESULTS: All
      DSM-IV alcohol abuse and dependence criteria, except alcohol-related legal
      problems, formed a continuum of alcohol use disorder severity. Abuse and
      dependence criteria did not consistently tap the mildest or more severe end of
      the continuum respectively, and several criteria were identified as potentially
      redundant. The drinking in larger amounts or for longer than intended dependence
      criterion had the greatest discrimination and lowest severity than any other
      criterion. Although several criteria were found to function differentially
      between subgroups defined in terms of sex and age, there was evidence that the
      generalizability and validity of the criterion forming the continuum remained
      intact at the test score level. CONCLUSIONS: DSM-IV diagnostic criteria for
      alcohol abuse and dependence form a continuum of severity, calling into question
      the abuse-dependence distinction in the DSM-IV and the interpretation of abuse as
      a milder disorder than dependence. The criteria tapped the more severe end of the
      alcohol use disorder continuum, highlighting the need to identify other criteria
      capturing the mild to intermediate range of the severity. The drinking larger
      amounts or longer than intended dependence criterion may be a bridging criterion
      between drinking patterns that incur risk of alcohol use disorder at the milder
      end of the continuum, with tolerance, withdrawal, impaired control and serious
      social and occupational dysfunction at the more severe end of the alcohol use
      disorder continuum. Future IRT and other dimensional analyses hold great promise
      in informing revisions to categorical classifications and constructing new
      dimensional classifications of alcohol use disorders based on the DSM and the
      ICD.

PMID- 16563206
TI  - Attribution style and psychosis: evidence for an externalizing bias in patients
      but not in individuals at high risk.
AB  - BACKGROUND: The aims of the study were to investigate whether (i) patients with
      lifetime presence of non-affective psychosis show an external-personal
      attribution bias for negative events, (ii) this attribution style can also be
      detected in first-degree relatives of patients with psychosis and subjects with
      subclinical psychotic experiences, and (iii) this attribution style is related to
      the presence of psychotic symptoms, in particular delusions. METHOD: Participants
      were 23 patients with lifetime presence of non-affective psychosis, a high- risk
      group of 36 first-degree relatives of patients with non-affective psychosis, a
      high-risk group of 31 subjects with subclinical psychotic experiences and 46
      normal controls. Attribution style was measured by the Internal, Personal and
      Situational Attribution Questionnaire. Positive symptoms were assessed with the
      Present State Examination (PSE) and the Scale for the Assessment of Positive
      Symptoms (SAPS). RESULTS: Relative to the controls, an externalizing bias was
      apparent in the patient group (beta = 0.20, p = 0.03) but not in the two high
      risk groups. There was a dose-response association between externalizing bias and
      the delusions subscale of the PSE (relative to lowest level: highest level of
      delusions: beta = 0.53, p = 0.04; intermediate levels of delusions: beta = 0.23,
      p = 0.35). No significant differences were found in personalizing bias between
      the four groups. CONCLUSIONS: Patients with psychosis tend to use an
      externalizing bias in their explanations of negative social events, and this bias
      is associated with the presence of positive psychotic symptoms, in particular
      delusions. A deviant attribution style is not part of the vulnerability to
      psychosis.

PMID- 16563207
TI  - Emotional dysfunction in schizophrenia spectrum psychosis: the role of illness
      perceptions.
AB  - BACKGROUND: Assessing illness perceptions has been useful in a range of medical
      disorders. This study of people with a recent relapse of their psychosis examines
      the relationship between illness perception, their emotional responses and their
      attitudes to medication. METHOD: One hundred patients diagnosed with a non
      affective psychotic disorder were assessed within 3 months of relapse. Measures
      included insight, self-reported illness perceptions, medication adherence,
      depression, self-esteem and anxiety. RESULTS: Illness perceptions about psychosis
      explained 46, 36 and 34% of the variance in depression, anxiety and self-esteem
      respectively. However, self-reported medication adherence was more strongly
      associated with a measure of insight. CONCLUSIONS: Negative illness perceptions
      in psychosis are clearly related to depression, anxiety and self-esteem. These in
      turn have been linked to symptom maintenance and recurrence. Clinical
      interventions that foster appraisals of recovery rather than of chronicity and
      severity may therefore improve emotional well-being in people with psychosis. It
      might be better to address adherence to medication through direct attempts at
      helping them understand their need for treatment.

PMID- 16563208
TI  - Integrated specialist assessment of older people and predictors of care-home
      admission.
AB  - BACKGROUND: Effective community-based care for older people requires the
      integration of assessment approaches by old age psychiatry, geriatric medicine
      and social services care management. This study examines the value of such
      collaboration in the assessment of older people at risk of entering care homes.
      METHOD: A randomized controlled trial of integrated assessment (care management
      with additional clinical assessment by old age psychiatrist or geriatrician)
      versus care management assessment only, for older people at risk of care-home
      admission. Older people's characteristics, physical and cognitive functioning,
      depression, behaviour and quality of care measures were recorded at assessment
      and 6 months. Differences in clinicians' and care managers' recommendations and
      placement rates between experimental and control groups were analysed. Logistic
      regression, examining associations between different needs-related
      characteristics and the likelihood of care-home admission, was used to
      characterize placement decisions. RESULTS: Clinicians recommended fewer older
      people for placement than did care managers in their usual assessments (a
      reduction of 85%). This did not, however, translate into a reduction in actual
      numbers of placements, although placements were delayed in those receiving the
      integrated assessment. Placements of those receiving the integrated assessment
      were influenced more by clinical factors, most notably cognitive impairment,
      which clinicians detected more readily than care managers. CONCLUSIONS: In this
      at-risk group, integrated assessment offers a means of potentially both delaying
      care-home admissions and taking account of a wider range of factors in placement
      decisions. Such an approach is viewed as an important policy goal both in the UK
      and internationally.

PMID- 16563217
TI  - Future perspectives in tissue engineering.

PMID- 16563218
TI  - Tissue engineering of bone: the reconstructive surgeon's point of view.
AB  - Bone defects represent a medical and socioeconomic challenge. Different types of
      biomaterials are applied for reconstructive indications and receive rising
      interest. However, autologous bone grafts are still considered as the gold
      standard for reconstruction of extended bone defects. The generation of
      bioartificial bone tissues may help to overcome the problems related to donor
      site morbidity and size limitations. Tissue engineering is, according to its
      historic definition, an "interdisciplinary field that applies the principles of
      engineering and the life sciences toward the development of biological
      substitutes that restore, maintain, or improve tissue function". It is based on
      the understanding of tissue formation and regeneration and aims to rather grow
      new functional tissues than to build new spare parts. While reconstruction of
      small to moderate sized bone defects using engineered bone tissues is technically
      feasible, and some of the currently developed concepts may represent alternatives
      to autologous bone grafts for certain clinical conditions, the reconstruction of
      large-volume defects remains challenging. Therefore vascularization concepts gain
      on interest and the combination of tissue engineering approaches with flap
      prefabrication techniques may eventually allow application of bone-tissue
      substitutes grown in vivo with the advantage of minimal donor site morbidity as
      compared to conventional vascularized bone grafts. The scope of this review is
      the introduction of basic principles and different components of engineered
      bioartificial bone tissues with a strong focus on clinical applications in
      reconstructive surgery. Concepts for the induction of axial vascularization in
      engineered bone tissues as well as potential clinical applications are discussed
      in detail.

PMID- 16563219
TI  - Relationships between neurokinin receptor-expressing interstitial cells of Cajal
      and tachykininergic nerves in the gut.
AB  - The so-called interstitial cells of Cajal (ICC) are distributed throughout the
      muscle coat of the alimentary tract with characteristic intramural location and
      species-variations in structure and staining. Several ICC sub-types have been
      identified: ICC-DMP, ICC-MP, ICC-IM, ICC-SM. Gut motility is regulated by ICC and
      each sub-type is responsible for the electrical activities typical of each gut
      region and/or muscle layer. The interstitial position of the ICC between nerve
      endings and smooth muscle cells has been extensively considered. Some of these
      nerve endings contain tachykinins. Three distinct tachykinin receptors (NK1r,
      NK2r and NK3r) have been demonstrated by molecular biology. Each of them binds
      with different affinities to a series of tachykinins (SP, NKA and NKB). In the
      ileum, SP-immunoreactive (SP-IR) nerve fibers form a rich plexus at the deep
      muscular plexus (DMP), distributed around SP-negative cells, and ICC-DMP
      intensely express the SP-preferred receptor NK1r; conversely a faint NK1r-IR is
      detected on the ICC-MP and mainly after receptor internalization was induced by
      agonists. ICC-IM are never stained in laboratory mammals, while those of the
      human antrum are NK1r- IR. RT-PCR conducted on isolated ileal ICC-MP and gastric
      ICC-IM showed that these cells express NK1r and NK3r. Colonic ICC, except those
      in humans, do not express NK1r-IR, at least in resting conditions. Outside the
      gut, NK1r-IR cells were seen in the arterial wall and exocrine pancreas. In the
      mouse gut only, NK1r-IR is present in non-neuronal cells located within the
      intestinal villi, so-called myoid cells, which are c-kit-negative and alpha
      smooth muscle actin-positive. Immunohistochemistry and functional studies
      confirmed that ICC receive input from SP-IR terminals, with differences between
      ICC sub-types. In the rat, very early after birth, NK1r is expressed by the ICC
      DMP and SP by the related nerve varicosities. Studies on pathological conditions
      are few and those on mutant strains practically absent. It has only been reported
      that in the inflamed ileum of rats the NK1r-IR ICC-DMP disappear and that at the
      peak of inflammatory conditions ICC-MP are NK1r-IR. In the ileum of mice with a
      mutation in the W locus, ICC-DMP were seen to express c-kit-IR but not NK1-IR,
      and SP-IR innervation seems unchanged. In summary, there are distinct ICC
      populations, each of them under a different tachykininergic control and, likely,
      having different functions. Further studies are recommended at the aim of
      understanding ICC involvement in modulating/transmitting tachykininergic inputs.

PMID- 16563220
TI  - Inwardly rectifying potassium channels (Kir) in central nervous system glia: a
      special role for Kir4.1 in glial functions.
AB  - Glia in the central nervous system (CNS) express diverse inward rectifying
      potassium channels (Kir). The major function of Kir is in establishing the high
      potassium (K+) selectivity of the glial cell membrane and strongly negative
      resting membrane potential (RMP), which are characteristic physiological
      properties of glia. The classical property of Kir is that K+ flows inwards when
      the RMP is negative to the equilibrium potential for K+ (E(K)), but at more
      positive potentials outward currents are inhibited. This provides the driving
      force for glial uptake of K+ released during neuronal activity, by the processes
      of "K+ spatial buffering" and "K+ siphoning", considered a key function of
      astrocytes, the main glial cell type in the CNS. Glia express multiple Kir
      channel subtypes, which are likely to have distinct functional roles related to
      their differences in conductance, and sensitivity to intracellular and
      extracellular factors, including pH, ATP, G-proteins, neurotransmitters and
      hormones. A feature of CNS glia is their specific expression of the Kir4.1
      subtype, which is a major K+ conductance in glial cell membranes and has a key
      role in setting the glial RMP. It is proposed that Kir4.1 have a primary function
      in K+ regulation, both as homomeric channels and as heteromeric channels by co
      assembly with Kir5.1 and probably Kir2.0 subtypes. Significantly, Kir4.1 are also
      expressed by oligodendrocytes, the myelin-forming cells of the CNS, and the
      genetic ablation of Kir4.1 results in severe hypomyelination. Hence, Kir, and in
      particular Kir4.1, are key regulators of glial functions, which in turn determine
      neuronal excitability and axonal conduction.

PMID- 16563221
TI  - Arteriogenesis versus angiogenesis: similarities and differences.
AB  - Cardiovascular diseases account for more than half of total mortality before the
      age of 75 in industrialized countries. To develop therapies promoting the
      compensatory growth of blood vessels could be superior to palliative surgical
      interventions. Therefore, much effort has been put into investigating underlying
      mechanisms. Depending on the initial trigger, growth of blood vessels in adult
      organisms proceeds via two major processes, angiogenesis and arteriogenesis.
      While angiogenesis is induced by hypoxia and results in new capillaries,
      arteriogenesis is induced by physical forces, most importantly fluid shear
      stress. Consequently, chronically elevated fluid shear stress was found to be the
      strongest trigger under experimental conditions. Arteriogenesis describes the
      remodelling of pre-existing arterio-arteriolar anastomoses to completely
      developed and functional arteries. In both growth processes, enlargement of
      vascular wall structures was proposed to be covered by proliferation of existing
      wall cells. Recently, increasing evidence emerges, implicating a pivotal role for
      circulating cells, above all blood monocytes, in vascular growth processes. Since
      it has been shown that monocytes/ macrophage release a cocktail of chemokines,
      growth factors and proteases involved in vascular growth, their contribution
      seems to be of a paracrine fashion. A similar role is currently discussed for
      various populations of bone-marrow derived stem cells and endothelial
      progenitors. In contrast, the initial hypothesis that these cells -after
      undergoing a (trans-)differentiation- contribute by a structural integration into
      the growing vessel wall, is increasingly challenged.

PMID- 16563222
TI  - Morphological aspects of apoptosis in heart diseases.
AB  - It has been suggested that apoptosis may be responsible for a significant amount
      of cardiomyocyte death during acute myocardial infarction as well as for a
      progressive loss of surviving cells in failing hearts. Typical apoptosis can
      indeed be induced in cardiomyocytes at the experimental conditions. In actual
      heart diseases, in contrast, there is very little direct morphological evidence
      of apoptosis in cardiomyocytes occurring at any stage of myocardial infarction
      and heart failure, despite the availability of much indirect evidence that
      includes detection of DNA fragmentation and apoptosis-related factors. For that
      reason, the potential efficacy of therapeutic intervention to prevent apoptosis
      remains controversial. This review will survey available data from both animals
      and humans to critically assess the role of cardiomyocyte apoptosis during
      myocardial infarction and its relevance to myocardial remodeling and during
      progression to heart failure. Also considered will be nonmyocyte interstitial
      cells, which have received less attention than myocytes despite definitive
      evidence of their apoptosis in the infarcted heart and recent studies suggesting
      that blockade of apoptosis among these cells mitigates postinfarction cardiac
      remodeling and heart failure. We conclude from our survey that there are many
      hurdles to surmount before regulation of apoptosis can be clinically applied in
      the treatment of myocardial infarction and heart failure.

PMID- 16563225
TI  - Discovery of the 'porosome'; the universal secretory machinery in cells.
AB  - The release of neurotransmitters at the nerve terminal for neurotransmission,
      release of insulin from beta-cells of the endocrine pancreas for regulating blood
      glucose levels, the release of growth hormone from GH cells of the pituitary
      gland to regulate body growth, or the expulsion of zymogen from exocrine pancreas
      to digest food, are only a few examples of key physiological processes made
      possible by cell secretion. It comes as no surprise that defects in cell
      secretion are the cause for numerous diseases, and have been under intense
      investigation for over half century. Only in the last decade, the molecular
      machinery and mechanism of cell secretion has become clear. Cell secretion
      involves the docking and transient fusion of membrane-bound secretory vesicles at
      the base of plasma membrane structures called porosomes, and the regulated
      expulsion of intravesicular contents to the outside, by vesicle swelling. The
      discovery of the porosome in live cells, its morphology and dynamics at nanometer
      resolution and in real time, its isolation, its composition, and its structural
      and functional reconstitution in lipid membrane, are complete. The molecular
      mechanism of secretory vesicle fusion at the base of porosomes, and the regulated
      expulsion of intravesicular contents during cell secretion, are also resolved. In
      this minireview, the monumental discovery of the porosome, a new cellular
      structure at the cell plasma membrane, is briefly discussed.

PMID- 16563223
TI  - Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF
      beta as major players and therapeutic targets.
AB  - Hepatic fibrosis is a scarring process that is associated with an increased and
      altered deposition of extracellular matrix in liver. At the cellular and
      molecular level, this progressive process is mainly characterized by cellular
      activation of hepatic stellate cells and aberrant activity of transforming growth
      factor-beta1 and its downstream cellular mediators. Although the cellular
      responses to this cytokine are complex, the signalling pathways of this pivotal
      cytokine during the fibrogenic response and its connection to other signal
      cascades are now understood in some detail. Based on the current advances in
      understanding the pleiotropic reactions during fibrogenesis, various inhibitors
      of transforming growth factor-beta were developed and are now being investigated
      as potential drug candidates in experimental models of hepatic injury. Although
      it is too early to favour one of these antagonists for the treatment of hepatic
      fibrogenesis in human, the experimental results obtained yet provide stimulatory
      impulses for the development of an effective treatment of choice in the not too
      distant future. The present review summarises the actual knowledge on the
      pathogenesis of hepatic fibrogenesis, the role of transforming growth factor-beta
      and its signalling pathways in promoting the fibrogenic response, and the
      therapeutic modalities that are presently in the spotlight of many investigations
      and are already on the way to take the plunge into clinical studies.

PMID- 16563226
TI  - SUMO-1 modification of MEF2A regulates its transcriptional activity.
AB  - Myocyte enhancer factor 2 (MEF2) transcription factors are crucial regulators
      controlling muscle-specific and growth factor-inducible genes. Numerous studies
      have reported that the activity of these transcription factors is tightly
      modulated by posttranslational modifications such as activation by specific
      phosphorylation as well as repression by class II histone deacetylases (HDACs).
      We hypothesized that MEF2 could also be regulated by covalent modification by
      SUMO-1, a reversible posttranslational modification which has been shown to
      regulate key proteins involved in cell proliferation, differentiation and tumor
      suppression. In this study, we demonstrate that MEF2A undergoes sumoylation
      primarily at a single lysine residue (K395) both in vitro and in vivo. We also
      show that the nuclear E3 ligase, PIAS1, promotes sumoylation of MEF2A. Mutation
      of lysine 395 to arginine abolishes MEF2A sumoylation and the sumoylation
      incompetent mutant protein has enhanced transcriptional activity compared to the
      wild type protein. Our results suggest that protein sumoylation could play a
      pivotal role in controlling MEF2 transcriptional activity.

PMID- 16563224
TI  - Epigenetics of prostate cancer: beyond DNA methylation.
AB  - Epigenetic mechanisms permit the stable inheritance of cellular properties
      without changes in DNA sequence or amount. In prostate carcinoma, epigenetic
      mechanisms are essential for development and progression, complementing,
      amplifying and diversifying genetic alterations. DNA hypermethylation affects at
      least 30 individual genes, while repetitive sequences including retrotransposons
      and selected genes become hypomethylated. Hypermethylation of several genes
      occurs in a coordinate manner early in carcinogenesis and can be exploited for
      cancer detection, whereas hypomethylation and further hypermethylation events are
      associated with progression. DNA methylation alterations interact with changes in
      chromatin proteins. Prominent alterations at this level include altered patterns
      of histone modification, increased expression of the EZH2 polycomb histone
      methyltransferase, and changes in transcriptional corepressors and coactivators.
      These changes may make prostate carcinoma particularly susceptible to drugs
      targeting chromatin and DNA modifications. They relate to crucial alterations in
      a network of transcription factors comprising ETS family proteins, the androgen
      receptor, NKX3.1, KLF, and HOXB13 homeobox proteins. This network controls
      differentiation and proliferation of prostate epithelial cells integrating
      signals from hormones, growth factors and cell adhesion proteins that are
      likewise distorted in prostate cancer. As a consequence, prostate carcinoma cells
      appear to be locked into an aberrant state, characterized by continued
      proliferation of largely differentiated cells. Accordingly, stem cell
      characteristics of prostate cancer cells appear to be secondarily acquired. The
      aberrant differentiation state of prostate carcinoma cells also results in
      distorted mutual interactions between epithelial and stromal cells in the tumor
      that promote tumor growth, invasion, and metastasis.

PMID- 16563228
TI  - N-acetyl-L-cysteine abrogates fibrogenic properties of fibroblasts isolated from
      Dupuytren's disease by blunting TGF-beta signalling.
AB  - Dupuytren's disease, a benign fibroproliferative disorder of the palmar fascia,
      represents an ideal model to study tissue fibrosis. Transforming growth factor
      beta1 (TGF-beta1) and its downstream Smad signalling system is well established
      as a key player during fibrogenesis. Thus, targeting this basic pathomechanism
      seems suitable to establish new treatment strategies. One such promising
      treatment involves the substance N-acetyl-L-cysteine (NAC), shown to have
      antifibrotic properties in hepatic stellate cells and rat fibroblasts. In order
      to investigate antifibrotic effects of N-acetyl-L-cysteine (NAC), fibroblasts
      were isolated from surgically resected fibrotic palmar tissues (Dupuytren
      fibroblasts, DF) and exposed to different concentrations of NAC and recombinant
      TGF-beta1. Fibroblasts isolated from tendon pulleys served as controls (control
      fibroblasts, CF). Smad signalling was investigated by a Smad binding element
      driven reporter gene analysis. Both cell types express TGF-beta1, indicating
      autocrine signalling in DF and CF. This was confirmed by comparing reporter gene
      activity from LacZ and Smad7 adenovirus infected cells. NAC treatment resulted in
      abrogation of Smad mediated signalling comparable to ectopically overexpressed
      Smad7, even when the cells were stimulated with recombinant TGF-beta1 or
      ectopically expressed a constitutively active TGF-beta receptor type I.
      Additionally, NAC dose-dependently decreased expression of three major indicators
      of impaired fibrotic matrix turnover, namely alpha-smooth muscle actin (alpha
      SMA), alpha 1 type I procollagen (Col1A1), and plasminogen activator inhibitor
      type I (PAI-1). Our results suggest that TGF-beta signalling and subsequent
      expression of fibrogenesis related proteins in Dupuytren's disease is abrogated
      by NAC thus providing a basis for a therapeutic strategy in Dupuytren's disease
      and other fibroproliferative disorders.

PMID- 16563227
TI  - Neuroglia in the inferior olivary nucleus during normal aging and Alzheimer's
      disease.
AB  - It is likely that neuronal loss occurs in certain brain regions in Alzheimer's
      Disease (AD) without any neurofibrillary pathology. In the human principle
      inferior olivary nucleus (PO), we have shown that neuronal loss is about 34%
      (Lasn et al. Journal of Alzheimer Disease, 2001; 3: 159-168), but the fate of the
      neuroglial cells is unknown. Since the unique network of neurons and neuroglial
      cells and their cohabitation are essential for normal functioning of CNS, we
      designed a study to estimate the total number of oligodendrocytes and astrocytes
      in normally aged and AD brains. The study is based on 10 control and 11 AD post
      mortem human brains. An unbiased stereological fractionator method was used. We
      found significant oligodendroglial cell loss (46%) in AD as compared to control
      brains, while the total number of astrocytes showed a tendency to decrease. It is
      likely that the ratio of oligodendroglial cells to neurons remains unchanged even
      in degenerative states, indicating that oligodendroglial cells parallel neuronal
      loss. Astroglial cells did not increase in total number, but the ratio to neurons
      was significantly increased due to the neuronal loss. Using a novel unbiased
      quantitative method, we were able to describe significant oligodendroglial loss
      in the PO but the pathogenic mechanism behind remains unknown.

PMID- 16563229
TI  - Ovariectomy ameliorates dextromethorphan--induced memory impairment in young
      female rats.
AB  - We have previously found that dextromethorphan (DM), over-the-counter cough
      suppressant, impairs memory retention in water maze task, when it is repeatedly
      administrated to adolescent female rats at high doses. In this study we examined
      first if ovariectomy ameliorates the DM-induced memory impairment in female rats,
      and then whether or not the DM effect is revived by estrogen replacement in
      ovariectomized female rats. Female rat pups received bilateral ovariectomy or
      sham operation on postnatal day (PND) 21, and then intraperitoneal DM (40 mg/kg)
      daily during PND 28-37. Rats were subjected to the Morris water maze task from
      PND 38, approximately 24 h after the last DM injection. In probe trial, goal
      quadrant dwell time was significantly reduced by DM in the sham operated group,
      however, the reduction by DM did not occur in the ovariectomy group. When 17beta
      estradiol was supplied to ovariectomized females during DM treatment, the goal
      quadrant dwell time was significantly decreased, compared to the vehicle control
      group. Furthermore, a major effect of estrogen replacement was found in the
      escape latency during the last 3 days of initial learning trials. These results
      suggest that ovariectomy may ameliorate the adverse effect of DM treatment on
      memory retention in young female rats, and that estrogen replacement may revive
      it, i.e. estrogen may take a major role in DM-induced memory impairment in female
      rats.

PMID- 16563231
TI  - A new scoring system using multiple immunohistochemical markers for diagnosis of
      uterine smooth muscle tumors.
AB  - The diagnosis of uterine smooth muscle neoplasms by light microscopy is
      difficult. Multiple classification schemes have been proposed based on mitotic
      rate, nuclear atypia, and the presence or absence of necrosis. None of these
      classification systems has been entirely successful. This study was undertaken to
      evaluate the use of selected immunohistochemical and histochemical markers in
      differentiating these tumors, in addition to accepted morphologic criteria. Ten
      cases of each of the following: leiomyosarcomas (LMS), atypical leiomyomas (AL),
      cellular leiomyomas (CL) and usual leiomyomas (UL), were classically evaluated
      for histological diagnosis and were stained for Ki-67 (MIB-1), bcl- 2 and p53
      using monoclonal antibodies and the avidin-biotin peroxidase method, and
      argyrophilic nucleolar organizer region (AgNORs). The number of stained cells was
      counted in the most positively stained region in a 4 mm2 square cover glass
      mounted on each slide. The mean value was calculated for each group of tumors.
      The data for Ki-67 (MIB- 1), bcl-2, p53 and AgNOR staining respectively, were
      significantly higher in LMS by comparison to UL, CL or AL. Because many singular
      cases had superimposed data being difficult to diagnose, a new scoring system for
      pathological evaluation was created. The results obtained by this scoring system
      suggest that immunohistochemical markers Ki-67 (MIB-1), bcl-2, p53 together with
      the AgNOR staining could be useful, by the scoring system, as an adjunct to the
      current accepted morphologic criteria in differentiating smooth muscle tumors of
      the uterus.

PMID- 16563230
TI  - The epigenetic reprogramming of poorly aggressive melanoma cells by a metastatic
      microenvironment.
AB  - A dynamic, complex relationship exists between tumor cells and their
      microenvironment, which plays a pivotal role in cancer progression, yet remains
      poorly understood. Particularly perplexing is the finding that aggressive
      melanoma cells express genes associated with multiple cellular phenotypes, in
      addition to their ability to form vasculogenic-like networks in three-dimensional
      matrix--called vasculogenic mimicry, which is illustrative of tumor cell
      plasticity. This study addressed the unique epigenetic effect of the
      microenvironment of aggressive melanoma cells on the behavior of poorly
      aggressive melanoma cells exposed to it. The data show significant changes in the
      global gene expression of the cells exposed to 3-D matrices preconditioned by
      aggressive melanoma cells, including the acquisition of a vasculogenic cell
      phenotype, upregulation of ECM remodeling genes, and increased invasive ability-
      indicative of an epigenetic, microenvironment-induced reprogramming of poorly
      aggressive melanoma cells. However, this epigenetic effect was completely
      abrogated when a highly cross-linked collagen matrix was used, which could not be
      remodeled by the aggressive melanoma cells. These findings offer an unique
      perspective of the inductive properties associated with an aggressive melanoma
      microenvironment that might provide new insights into the epigenetic regulation
      of tumor cell plasticity and differentiation, as well as mechanisms that could be
      targeted for novel therapeutic strategies.

PMID- 16563232
TI  - Age-associated changes in oxidative damage and the activity of antioxidant
      enzymes in rats with inherited overgeneration of free radicals.
AB  - Reactive oxygen species have been hypothesized to play an important role in the
      process of aging. To investigate the correlation between oxidative stress and
      accumulation of protein and DNA damage, we have compared the age-dependent levels
      of protein carbonyl groups and the activities of antioxidant enzymes superoxide
      dismutase, catalase and glutathione peroxidase in cytosol and mitochondrial
      extracts from liver cells of Wistar and OXYS rats. The latter strain is
      characterized by increased sensitivity to free radicals. Faster age-dependent
      increase in the level of protein carbonyl groups was found in OXYS as compared
      with Wistar rats. A complicated enzyme-specific pattern of age-dependent changes
      in the activities of antioxidant enzymes was observed. Long-term uptake of
      dietary supplements Mirtilene forte (extract from the fruits of Vaccinium
      myrtillus L.) or Adrusen zinco (vitamin E complex with zinc, copper, selenium and
      omega-3 polyunsaturated fatty acids) sharply decreased the level of protein
      oxidation in cytosol and mitochondrial extracts of hepatocytes of Wistar and of
      OXYS rats. Both dietary supplements increased the activity of catalase in the
      liver mitochondria of OXYS rats. Our results are in agreement with the shorter
      life-span of OXYS and with the mitochondrial theory of aging, which postulates
      that accumulation of DNA and protein lesions leads to mitochondrial dysfunction
      and accelerates the process of aging.

PMID- 16563233
TI  - Caveolin-3 inhibits growth signal in cardiac myoblasts in a Ca2+-dependent
      manner.
AB  - Caveolin, a major protein component of caveolae, directly interacts with multiple
      signaling molecules, such as Ras and growth factor receptors, and inhibits their
      function. However, the role of the second messenger system in mediating this
      inhibition by caveolin remains poorly understood. We examined the role of Ca2+
      dependent signal in caveolin- mediated growth inhibition using a rat cardiac
      myoblast cell line (H9C2), in which the expression of caveolin- 3, the muscle
      specific subtype, can be induced using the LacSwitch system. Upon induction with
      IPTG and serum-starvation, the expression of caveolin-3 was increased by 3.3-fold
      relative to that of mock-induced cells. The recombinant caveolin-3 was localized
      to the same subcellular fraction as endogenous caveolin-3 after sucrose gradient
      purification. Angiotensin II enhanced ERK phosphorylation, but this enhancement
      was significantly decreased in caveolin-3-induced cells in comparison to that in
      mock-induced cells. Similarly, when cells were stimulated with fetal calf serum,
      DNA synthesis, as determined by [3H]-thymidine incorporation, was significantly
      decreased in caveolin- 3-induced cells. When cells were treated with Ca2+
      chelator (BAPTA and EGTA), however, this attenuation was blunted. Calphostin (PKC
      inhibitor), but not cyclosporine A treatment (calcineurin inhibitor), blunted
      this attenuation in caveolin-3 induced cells. Our findings suggest that caveolin
      exhibits growth inhibition in a Ca2+-dependent manner, most likely through PKC,
      in cardiac myoblasts.

PMID- 16563234
TI  - Dobesilate diminishes activation of the mitogen-activated protein kinase ERK1/2
      in glioma cells.
AB  - Fibroblast growth factors (FGFs) and their receptors, regularly expressed at high
      levels in gliomas, are further upregulated during the transition of the tumor
      from low- to high-grade malignancy, and are essential for glioma progression.
      FGFs induce upregulation of the mitogen-activated protein kinase (MAPK) signaling
      cascade in cultured glioma cells, which suggests that MAPK pathway participates
      in the FGF-dependent glioma development. Recently, it has been shown that
      dobesilate, an inhibitor of FGF mitogenic activity, shows antiproliferative and
      proapoptotic activities in glioma cell cultures. Accordingly, it should be
      expected this new synthetic FGF inhibitor to affect the activation levels of
      MAPK. Here we report that immunocytochemical and Western blot data unequivocally
      show that treatment of cell cultures with dobesilate causes a significant
      decrease of the intracellular levels of ERK1/2 activation, one of the components
      of the MAPK signalling cascade. This finding supports an important role for
      dobesilate in glioma growth, suggesting that dobesilate should be a treatment to
      be born in mind for glioma management.

PMID- 16563236
TI  - Hypothalamic osteolipoma of the tuber cinereum.

PMID- 16563235
TI  - Differential upregulation of Nox homologues of NADPH oxidase by tumor necrosis
      factor-alpha in human aortic smooth muscle and embryonic kidney cells.
AB  - NADPH oxidases are important sources of vascular superoxide, which has been
      linked to the pathogenesis of atherosclerosis. Previously we demonstrated that
      the Nox4 subunit of NADPH oxidase is a critical catalytic component for
      superoxide production in quiescent vascular smooth muscle cells. In this study we
      sought to determine the role of Nox4 in superoxide production in human aortic
      smooth muscle cells (AoSMC) and embryonic kidney (HEK293) cells under
      proinflammatory conditions. Incubation with tumor necrosis factor-alpha (TNF
      alpha, 10 ng/ml) for 12 h increased superoxide production in both cell types,
      whereas angiotensin II, platelet-derived growth factor or interleukin-1beta had
      little effects. Superoxide production was completely abolished by the NADPH
      oxidase inhibitors diphenyline iodonium and apocynin, but not by inhibitors of
      xanthine oxidase, nitric oxide synthase or mitochondrial electron transport. TNF
      alpha upregulated the expression of Nox4 in AoSMC at both message and protein
      levels, while Nox1 and Nox2 were unchanged. In contrast, upregulation of Nox2
      appeared to mediate the enhanced superoxide production by TNF-alpha in HEK293
      cells. We suggest that Nox4 may be involved in increased superoxide generation in
      vascular smooth muscle cells under proinflammatory conditions.

PMID- 16563238
TI  - [More in-depth investigation for the catheter ablation treatment of atrial
      fibrillation is needed].

PMID- 16563237
TI  - Interstitial Cajal-like cells (ICLC) in atrial myocardium: ultrastructural and
      immunohistochemical characterization.
AB  - We have previously reported (Hinescu & Popescu, 2005) the existence of
      interstitial Cajal-like cells (ICLC), by transmission electron microscopy, in
      human atrial myocardium. In the present study, ICLC were identified with non
      conventional light microscopy (NCLM) on semi-thin sections stained with toluidine
      blue and immunohistochemistry (IHC) for CD117/c-kit, CD34, vimentin and other
      additional antigens for differential diagnosis. Quantitatively, on semi-thin
      sections, ICLC represent about 1-1.5% of the atrial myocardial volume (vs.
      approximately 45% working myocytes, approximately 2% endothelial cells, 3-4% for
      other interstitial cells, and the remaining percentage: extracellular matrix).
      Roughly, there is one ICLC for 8-10 working atrial myocytes in the intercellular
      space, beneath the epicardium, with a characteristic (pyriform, spindle or
      triangular) shape. These ICLC usually have 2-3 definitory processes, emerging
      from cell body, which usually embrace atrial myocytes (260 nm average distance
      plasmalemma/sarcolemma) or establish close contact with nerve fibers or
      capillaries (approximately 420 nm average distance to endothelial cells). Cell
      prolongations are characteristic: very thin (mean thickness = 0.15+/-0.1 microm),
      very long for a non-nervous cell (several tens of microm) and moniliform (uneven
      caliber). Stromal synapses between ICLC and other interstitial cells
      (macrophages) were found (e.g. in a multicontact type synapse, the average
      synaptic cleft was approximately 65 nm). Naturally, the usual cell organelles
      (mitochondria, smooth and rough endoplasmic reticulum, intermediate filaments)
      are relatively well developed. Caveolae were also visible on cell prolongations.
      No thick filaments were detected. IHC showed that ICLC were slightly and
      inconsistently positive for CD117/c-kit, variously co-expressed CD34 and EGF
      receptor, but appeared strongly positive for vimentin, along their prolongations.
      Some ICLC seemed positive for a-smooth muscle actin and tau protein, but were
      negative for nestin, desmin, CD13 and S-100. In conclusion, we provide further
      evidence of the existence of ICLC in human atrial myocardium, supporting the
      possible ICLC role in pacemaking, secretion (juxta- and/or paracrine),
      intercellular signaling (neurons and myocytes). For pathology, ICLC might as well
      be 'players' in arrhythmogenesis and atrial remodeling.

PMID- 16563239
TI  - [Left atrium linear lesion encircling pulmonary veins guided by EnSite-NavX and
      double-Lasso technique for paroxysmal atrial fibrillation].
AB  - OBJECTIVE: To evaluate the efficacy of left atrium linear lesion encircling
      pulmonary veins (PV) guided by EnSite-NavX and double-Lasso technique for
      paroxysmal atrial fibrillation (PAF). METHODS: Twenty-two patients (male 19, mean
      age of 48.5 years +/- 11.4 years) with symptomatic PAF were enrolled. After a
      geometry of the left atrium was reconstructed by EnSite-NavX system, PV ostia
      were marked on the map based on venography. Two Lasso catheters were placed
      within the ipsilateral superior and inferior PVs. Irrigated radiofrequency energy
      was applied at 0.5-1.0 cm of distance from the PV ostia. Continuous linear lesion
      was done to obtain the disappearance of pulmonary vein potentials. Patients were
      on propafenone and perindopril for three months after the procedure. RESULTS: The
      endpoint for ablation was reached in 21 Patients and 1 patient was not successful
      because of cardiac tamponade. The mean procedure time was 6.6 h +/- 1.3 h and the
      mean X-ray exposure time was 56.1 min +/- 18.0 min. After a mean 5.3 months +/-
      2.7 months of follow-up, 10 patients were free of symptoms. Two patients had no
      PAF recurrence after the second procedure. Three patients had clinical recurrence
      of PAF in the first month. The total success rate in this study was 81% (17/21).
      Mortality was 0% and the overall complication rate was about 9% (2/22).
      CONCLUSION: Left atrium circumferential linear ablation surrounding PV ostia
      guided by EnSite-NavX and double-Lasso technique is effective in PAF, but some
      patients will need more than one procedure in order to achieve a success.

PMID- 16563240
TI  - [Electroanatomical systems guided circumferential pulmonary veins ablation for
      atrial fibrillation: initial experience from comparison between the EnSite-NavX
      and CARTO system].
AB  - OBJECTIVE: The circumferential pulmonary vein ablation (CPVA) has been proved
      effective for atrial fibrillation (AF) and is becoming more widely accepted. This
      study aims to evaluate the effectiveness of the CARTO and the EnSite-NavX system
      and to compare between them on procedural parameters and clinical
      characteristics. METHODS: Seventy-five patients with paroxysmal or persistent
      symptomatic AF were randomly assigned to CPVA procedure guided by either the
      EnSite-NavX system (group I, n = 40) or the CARTO system (group II, n = 35).
      After successful transseptal procedure, a geometry of left atrium was created
      under the guidance of the two systems. Radiofrequency energy was applied to
      circumferential tissues out of pulmonary veins (PVs) ostia. In cases with
      persistent AF, linear ablation was applied to modify the substrate of LA. The
      endpoint of the procedure was complete PVs isolation. RESULTS: Seventy-four cases
      underwent a successful procedure. The total procedure and fluoroscopic time in
      group II was significantly shorter than those in group I (150 min +/- 23 min and
      18 min +/- 17 min vs 170 min +/- 34 min and 25 min +/- 16 min, P = 0.03 and 0.04,
      respectively). There was no significant difference in the fluoroscopic and
      procedure durations for geometry creation between the groups I and II (8 min +/-
      4 min and 16 min +/- 11 min vs 5 min +/- 4 min and 14 min +/- 8 min,
      respectively). The fluoroscopic time for CPVA was 15 min +/- 5 min in group I vs
      10 min +/- 6 min in group II (P = 0.05), and the CPVA procedural durations were
      significantly shorter in group II than those in group (86 min +/- 11 min vs 110
      min +/- 15 min, P = 0.04). AF was terminated by RF delivery in 14 cases (35%) in
      group Ivs 5 cases (14%) in group II (P = 0.04). Complete PV isolation was
      obtained in 26 cases (65%) in group Ivs 11 cases (31%) in group II (P = 0.004).
      During a mean follow-up of 7 months, 32 (80%) cases in group I and 24 (69%) cases
      in group II were arrhythmia-free (P = 0.06). One case developed pericardial
      tamponade and 1 case was found to have intestinal artery thrombosis in group II.
      One case had moderate hemothorax in group I. All the complications were cured and
      no PV stenosis was observed. CONCLUSIONS: The CPVA procedure for atrial
      fibrillation is effective and safe. Although there is a difference between the
      CARTO and the EnSite-NavX system, the CPVA procedure guided by either of them
      yields similar clinical results.

PMID- 16563241
TI  - [Comparison of different pulmonary vein isolation strategies for patients with
      paroxysmal atrial fibrillation].
AB  - OBJECTIVE: To compare two catheter ablation strategies for pulmonary vein (PV)
      isolation in patients with paroxysmal atrial fibrillation (PAF). METHODS: Fifty
      consecutive patients who underwent PV isolation by circumferential PV ablation
      (CPVA group) were compared with 50 consecutive patients who underwent PV
      isolation by segmental PV ablation (SPVA group). The enrolled subjects in this
      retrospective study were patients with frequent attacks (more than 3 times per
      month) and symptomatic PAF. Procedure-related parameters, safety and clinical
      outcome within 6 months after procedures for the 2 strategies were analyzed.
      RESULTS: The characteristics and mean procedure time were comparable between the
      2 groups. The mean fluoroscopy time and mean ablation time were 57 min +/- 11 min
      and 42 min +/- 9 min in the SPVA group and 31 min +/- 8 min and 61 min +/- 13 min
      in the CPVA group (both P < 0.01), respectively. After the first procedure,
      symptomatic atrial tachyarrhythmias (ATa) recurred in 24 (48%) of 50 patients who
      underwent SPVA and 15 (30%) of 50 patients who underwent CPVA within 3 months (P
      = 0.10). During 6 months of follow-up, 82% of patients with CPVA and 60% of
      patients with SPVA were free of symptomatic ATa without any antiarrhythmic drugs
      for at least 3 months (P < 0.05). One patient per each group developed
      asymptomatic right superior PV stenosis. CONCLUSION: In patients with PAF, CPVA
      compares favorably with SPVA, but either of them yields a similar clinical
      safety.

PMID- 16563242
TI  - [Clinical efficacy of endoscopic epicardial microwave ablation for isolated
      atrial fibrillation].
AB  - OBJECTIVE: To assess the efficacy of endoscopic epicardial microwave ablation, a
      new completely endoscopic technique, for isolated atrial fibrillation (AF).
      METHODS: From July to October of 2004, 5 patients with isolated permanent AF
      underwent this procedure. We performed epicardial microwave ablation using FLEX10
      probe under the guide of VasoView 5 endoscope. The probe was placed around left
      and right pulmonary vein orifices, the microwave application was set 65 W/90 s,
      and a continuous ablation line was obtained encircling the pulmonary veins.
      Echocardiography and electrocardiography were carried out in all patients before
      and after operation. RESULTS: Five patients received electrical conversion after
      ablation. Average ablation time was 35.0 min and average procedure time was 2.5 h
      without any procedure-related complications. At the 3-month, 6-month and 12-month
      follow-up, 4 patients (80%) were in sinus rhythm, associated with a reduced left
      atrial diameter and an improved cardiac function. CONCLUSION: Endoscopic
      epicardial microwave ablation for isolated atrial fibrillation appears to be safe
      and effective.

PMID- 16563243
TI  - [The association of single nucleotide polymorphism of slow delayed rectifier K+
      channel genes with atrial fibrillation in Han nationality Chinese].
AB  - OBJECTIVE: To investigate the association between atrial fibrillation and the
      single nucleotide polymorphism (SNP) of slow delayed rectifier K(+) channel
      (I(Ks)) genes in Han nationality Chinese. METHODS: Three hundred and eighty of
      Han nationality Chinese (142 atrial fibrillation, 120 in-hospital and 118 out
      hospital control) were enrolled in this study. Asian specific non-synonymous SNPs
      of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N were
      genotyped by restriction fragment length polymorphism analysis. A newly cloned
      KCNE4 gene was also screened for any possible SNP. RESULTS: The minor allele
      frequency of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N in
      out-hospital subjects was 0.079, 0, 0.042, 0.317 and 0.004, respectively. None of
      these SNPs was relationed with any atrial fibrillation phenotype. A KCNE4 E145D
      was discovered and proven statistically to relation significantly to atrial
      fibrillation by logistic regression analysis (OR = 1.66, P = 0.044). The minor
      allele frequency of KCNE4 E145D was as high as 0.271 in out-hospital subjects.
      CONCLUSIONS: None of the SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1
      G38S and KCNE1 D85N was associated with atrial fibrillation phenotype, but KCNE4
      E145D may relation to atrial fibrillation. The effect of KCNE4 E145D variation on
      the function of I(Ks) channel is to be determined.

PMID- 16563244
TI  - [Effects of atrial excitable period on the stability of atrial fibrillation in
      goats].
AB  - OBJECTIVE: To investigate the effects of atrial excitable period (EP) on the
      stability of atrial fibrillation (AF) in goats. METHODS: Ten female goats were
      instrumented with epicardial electrodes patches on the left atrium (LA) free
      wall. AF was induced and maintained by a home-made stimulator with frequency of
      50 Hz at a 1-second duration and a 2-seconds interval. The stimulator was
      disconnected regularly. AF-induced duration, average AF cycle length (AFCL), and
      atrial effective refractory period during AF (ERP(AF)) were measured; EP was
      calculated by AFCL-ERP(AF). RESULTS: Eight goats were studied. Persistent AF (>
      24 h) could be induced in all the 8 goats within 6-16 days. When the induced AF
      lasted for 3-10 min or 24 h, the AFCL was 98.3 ms +/- 11.0 ms and 84.9 ms +/- 5.2
      ms (P < 0.05), respectively, ERP(AF) was 90.5 ms +/- 13.2 ms and 63.0 ms +/- 4.8
      ms (P < 0.05), respectively, and EP was 7.8 ms +/- 2.4 ms and 21.9 ms +/- 3.5 ms
      (P < 0.05), respectively. CONCLUSION: The decrease in ERP(AF) is more significant
      than the shortening in AFCL, resulting in the gradually widening of EP which may
      contribute to the perpetuation of AF.

PMID- 16563245
TI  - [Effects of carvedilol on neurohormone and magnesium metabolism in patients with
      chronic heart failure].
AB  - OBJECTIVE: To investigate the effects of carvedilol on neurohormone and magnesium
      metabolism in patients with chronic heart failure (CHF). METHODS: Fifty-seven
      patients with CHF were divided into two groups randomly: received conventional
      treatment alone or combined with carvedilol for 8 weeks, respectively. Urine
      magnesium excretion (UME), plasma levels of magnesium (PMC), norepinephrine (NE),
      angiotensin-II (Ang-II), aldosterone (ALD), plasma renin activity (PRA) and
      peripheral monocyte magnesium content (MMC) were measured before and after
      treatments. Twenty-six health persons were selected as normal subjects. RESULTS:
      There was a significant increase in UME and plasma concentrations of NE, ALD, Ang
      II and PRA, and a significant decrease in MMC in patients with CHF, compared with
      the control group (P < 0.01). UME was positively correlated with ALD, Ang-II, PRA
      r = 0.41, 0.42, 0.38, respectively (P < 0.01). These parameters significantly
      improved after carvedilol (P < 0.05). CONCLUSION: Carvedilol decreases
      significantly plasma concentrations of neurohormone and urine magnesium
      excretion, and increases cell magnesium content in patients with CHF.

PMID- 16563246
TI  - [Noncontact endocardial mapping to guide ablation for hemodynamically unstable or
      nonsustained ventricular tachycardia].
AB  - OBJECTIVE: To determine the feasibility and assess the validity of noncontact
      endocardial mapping to guide ablation of hemodynamically unstable or nonsustained
      ventricular tachycardia (VT). METHODS: Noncontact mapping permitted individual
      beat analysis of ventricular arrhythmias. Three-dimensional electroanatomical
      mapping allowed detailed reconstruction of a chamber geometry and activation
      sequence. Eighteen hemodynamically unstable or nonsustained VTs were induced
      (cycle length: 336 ms +/- 58 ms) in 17 patients and mapped by noncontact mapping
      using an EnSite 3000 system performed for the guidance of catheter ablation.
      RESULTS: Three patients were mapped during premature ventricular complexes (PVCs)
      because sustained VT could not be induced. Analysis of the archived noncontact
      activation maps was performed to identify the exit site and/or the diastolic
      pathway of the VT reentry circuit. The endocardial exit sites 10 ms +/- 16 ms
      before QRS were defined in 9 right ventricular outflow tract (RVOT) and 5
      ischemic VTs. The diastolic pathway was identified in 5 ischemic VTs. The
      earliest endocardial diastolic activity preceded the QRS onset by 60.1 ms +/-
      42.6 ms. The earliest activation sites were identify in 3 patients with
      nonsustained VTs or PVCs. Radiofrequency current was applied around the exit site
      or to create a line of block across the diastolic pathway. Catheter ablation was
      performed in 17/18 (94%) VTs and 15/17 (88%) VTs was successfully ablated. Two
      (67%) of the three patients with non-sustained VTs were mapped and successfully
      ablated during PVCs. Catheter ablation was not performed in 1 patient (peri
      Hisian VT) and was unsuccessful in 2 patients. CONCLUSION: Noncontact endocardial
      mapping is able to be used to guide ablation of untolerated or nonsustained VTs.

PMID- 16563247
TI  - [Comparison of different pacing sites of the right ventricle on left ventricular
      mechanical synchrony and systolic performance using tissue Doppler imaging].
AB  - OBJECTIVE: Right ventricular apical pacing may induce cardiac desynchronize and
      deteriorate left ventricular systolic performance. We hypothesized that right
      ventricular outflow tract (RVOT) pacing could produce better mechanical synchrony
      and left ventricular contraction. METHODS: We enrolled nine patients without
      structural heart disease who underwent electrophysiological studies. The pacing
      sites (right apex, low septum, free wall and septum of RVOT of the right
      ventricle) were defined with fluoroscopy and ECG. The atrioventricular sequential
      pacing was applied every 5 minutes in a random order at a rate of 120 bpm. Tissue
      Doppler imaging was carried out with GE VIVID 7 for off-line analysis at each
      pacing site. The global systolic contraction amplitude (GSCA) was calculated as
      the average shortening amplitude of all 16 segments of left ventricle. RESULTS:
      The GSCA during pacing was 5.76 mm +/- 0.66 mm at free wall of RVOT and 5.66 mm
      +/- 1.00 mm at septum of RVOT, respectively. The GSCA at both sites was
      significantly higher than that at apical pacing 4.82 mm +/- 0.94 mm (P < 0.05) or
      low septum pacing 4.82 mm +/- 1.06 mm (P < 0.05). Moreover, segmental
      displacement analysis showed that the longitudinal displacement of lateral,
      posterior, and inferior walls significantly decreased at apical pacing compared
      with RVOT pacing, although no difference could be demonstrated in anterior and
      septum walls. Accordingly, the curve of the myocardial displacement at apical or
      low septum pacing was M-shaped, and had a negative wave at the end of the
      diastole in lateral, posterior, and inferior walls. The tissue velocity during
      isovolumic contraction period was also higher than systolic tissue velocity in
      these walls. The phenomenon could seldom be seen at RVOT pacing. CONCLUSION: RVOT
      pacing in patients without structural heart disease is associated with more
      favorable immediate myocardial contraction and mechanical synchrony compared with
      right apical pacing or low septum pacing.

PMID- 16563248
TI  - [Effect of neuropeptide Y and neurotensin on diurnal rhythm of blood pressure and
      target organ damage for essential hypertension].
AB  - OBJECTIVE: To investigate the effect of plasma neuropeptide Y (NPY), neurotensin
      (NT) and their relationships on the diurnal rhythm of BP and target organ damage
      for essential hypertension. METHODS: Ambulatory BP monitoring (ABPM) for 24 hours
      was performed in ninety patients with essential hypertension and thirty healthy
      subjects. The patients were divided into two groups: 55 dippers and 35 non
      dippers according to the ABPM results. Plasma NPY and NT levels in subjects were
      measured at 8:00, 16:00 and 2:00 o'clock by using radioimmunoassay method. Target
      organ functions were measured. RESULTS: The plasma NPY level was higher and NT
      was lower in patients with hypertension those in normal controls (P < 0.001).
      Compared with dippers, non-dippers had a higher NPY and a lower NT plasma levels,
      especially appearing at 2:00 o'clock. The patients with left ventricular
      hypertrophy, stroke or kidney damage had a higher NPY and a lower NT levels
      compares with those without target organ damage. CONCLUSION: The changes in
      plasma NPY and NT may contribute to disturbance of the diurnal rhythm of blood
      pressure in patients with essential hypertension, especially in those with target
      organ damages, which may serve as a pathophysiologic mechanism for target organ
      damages in hypertension.

PMID- 16563249
TI  - [The impact of gender factor on the candidate gene study of essential
      hypertension].
AB  - OBJECTIVE: To study the impact of gender factor on the candidate gene study of
      essential hypertension (EH). METHODS: The polymerase chain reaction (PCR) was
      performed to analyze the ACE gene I/D polymorphism of hypertensive patients (50
      men and 50 women) and normal controls (50 men and 50 women). The investigation
      was further focused on possible influence of sex proportion on the conclusion of
      this kind of research. RESULTS: The frequency of DD genotype in male hypertensive
      patients is significantly higher than that in male normal controls (chi(2) =
      6.98, P = 0.004). The frequency of D allele in male EH group is significantly
      higher than that of male normal controls (chi(2) = 6.87, P = 0.009), while no
      significant difference was observed for II and ID genotype between male EH group
      and control group (P > 0.05). For female EH group and normal controls, there were
      no significant differences in frequency of genotype and allele (P > 0.05), the
      distribution ratio of DD genotype in male EH group is significantly different
      from that of female EH group (chi(2) = 4.06, P = 0.044). Furthermore, males with
      DD genotype in EH group had higher SBP and PP than that of males with II and ID
      genotype (P < 0.05). However, there was no significant difference in DBP in all
      three genotypes (P > 0.05). At the same time, there was no difference in SBP, DBP
      and PP (P > 0.05) between II and ID genotype in male EH group. In female
      hypertensive patients, there was no significant difference in SBP, DBP and PP
      between all three genotypes (P > 0.05). CONCLUSIONS: The relationship between DD
      genotype in male and EH (especially SBP and PP) is closer than any other genotype
      EH relationships in both male and female. The gender factor, as a probable
      confounding factor, can affect many candidate gene studies of essential
      hypertension including ACE gene I/D polymorphism, and thus biases the conclusion.

PMID- 16563250
TI  - [Change in endothelial progenitor cells and endothelial function in patients with
      unstable angina pectoris].
AB  - OBJECTIVE: To investigate the relationship between endothelial progenitors cells
      (EPCs) and endothelium-dependent vasodilation in patients with unstable angina
      pectoris. METHODS: Thirty patients with unstable angina pectoris (UAP) and thirty
      control subjects were recruited. Flow-mediated dilation (FMD) in the brachial
      artery was evaluated by using ultrasound Doppler flow method. The number of
      circulating EPCs was analyzed by flow cytometry analysis. Total mononuclear cells
      were isolated from peripheral blood by Ficoll density gradient centrifugation,
      and then the cells were plated on fibronectin-coated culture dishes. CD34 antigen
      of adherent cells was identified by immunohistochemical assay. EPCs were
      characterized as adherent cells double positive for FITC-UEA-I binding and DiI
      acLDL uptake by direct fluorescent staining under inverted fluorescent
      microscope. RESULTS: FMD was significantly impaired in the UAP group compared
      with the control group (5.93% +/- 2.67% vs 11.1% +/- 4.36%, P < 0.05). There was
      no significant difference in NMD between two groups (13.60% +/- 5.03% vs 14.18%
      +/- 4.50%, P > 0.05). The number of CD34(+) cells significantly increased in the
      UAP group compared with the control group (0.13% +/- 0.05% vs 0.09% +/- 0.04%, P
      < 0.05). There was a negative association between impaired FMD and increased
      CD34(+) cell (r = -0.385, P < 0.05). A positive antigen of CD34 of adhesion cells
      and double positive adhesion cells were found. CONCLUSION: This study shows that
      the levels of peripheral CD34(+) cells in patients with UAP increase with an
      impaired endothelial function. The increase in EPCs may be an important
      compensatory response to acute coronary ischemia and impaired endothelium in
      patients with UAP.

PMID- 16563251
TI  - [Atorvastatin reduces the expression of COX-2 mRNA in peripheral blood monocytes
      in patients with acute myocardial infarction and modulates the early inflammatory
      response].
AB  - OBJECTIVE: To measure the effect of atorvastatin on COX-2 expression in monocytes
      in patients with acute myocardial infarction (AMI). METHODS: Forty patients with
      AMI (AMI group) and 18 patients with stable coronary heart disease (control
      group) were enrolled, and patients with AMI were randomly given routine therapy
      (n = 20) and routine therapy plus atorvastatin (20 mg/day, n = 20) for a week.
      Peripheral blood monocytes for each participant including patients with AMI were
      isolated and cultured for 24 hours. During the culture, monocytes in patients
      with pretreatment AMI were incubated with celecoxib in different concentration
      (0, 0.1, 1 and 10 micromol/L). COX-2 mRNA expression in monocytes was measured by
      reverse transcription polymerase chain reaction (RT-PCR); concentrations of
      interleukin-6 (IL-6) in supernatant from monocytes and plasma hs-CRP levels were
      measured by using enzyme-linked immunosorbent assay (ELISA). RESULTS: COX-2
      expression in monocytes in patients with AMI (0.92 +/- 0.13) was significantly
      higher than that in the control subjects (0.19 +/- 0.08), and decreased by 66%
      after atorvastatin (compared with that on routine therapy, P < 0.05); IL-6
      secretions of monocytes in the AMI group (204.8 +/- 45.6 ng/L) increased
      dramatically compared with those in the control group (40.9 +/- 1.2 ng/L, P <
      0.05), and reduced dramatically by 58% when incubated with 10 micromol/L
      celecoxib (P < 0.05) in a concentration-dependent manner; plasma levels of CRP in
      the AMI group (43.3 +/- 14.9 mg/L) significantly increased compared with those in
      the control group (1.7 +/- 0.8 mg/L), and reduced by 62% after atorvastatin
      (compared with those in the routine therapy group, P < 0.05). COX-2 expression in
      monocytes in the AMI group was positively correlated with both secretions of IL-6
      and plasma level of CRP (r = 0.636 and 0.662, respectively, both P < 0.05).
      CONCLUSIONS: There is an inflammatory activation in peripheral blood monocytes in
      patients with early AMI, and the monocytes-derived COX-2 may play an important
      role in promoting early inflammatory process. Atorvastatin may decrease COX-2
      expression in peripheral blood monocytes in patients with AMI and cyclooxygenase
      dependent pathway might be correlated with the anti-inflammation mechanism of
      statin.

PMID- 16563252
TI  - [Clinical significance of adenosine 99mTc-MIBI myocardial perfusion single photon
      emission computed tomography for patients in percutaneous coronary intervention].
AB  - OBJECTIVE: To analyze the clinical significance of adenosine (99m)Tc-MIBI
      myocardial perfusion single photon emission computed tomography (SPECT) in
      patients with coronary artery disease (CAD) for percutaneous coronary
      intervention (PCI). METHODS: Coronary angiography and adenosine (99m)Tc-MIBI
      myocardial perfusion SPECT were performed for all patients. Adenosine myocardial
      perfusion was performed after PCI. Adenosine was infused intravenously at a rate
      of 140 microg.kg(-1).min(-1) for 6 minutes, and 925MBq (99m)Tc-MIBI was injected
      intravenously at 3 minutes after adenosine infusion. SPECT myocardial imaging
      acquisition was obtained in 1.5 hours after adenosine infusion. If the result was
      abnormal, rest (99m)Tc-MIBI myocardial perfusion SPECT would be performed next
      day. There were 17 segments of left ventricle, and four degrees of myocardial
      perfusion. RESULTS: There were 63 cases (63 +/- 10 years old) with CAD, in which
      40 patients got PCI. Twenty eight cases after PCI. CONCLUSION: Adenosine
      myocardial perfusion imaging will be useful in detecting regional myocardial
      perfusion abnormalities for patients with PCI.

PMID- 16563254
TI  - [The role of first pass and delayed contrast-enhancement magnetic resonance
      imaging in patients with myocardial infarction].
AB  - OBJECTIVE: To evaluate the role of contrast-enhancement magnetic resonance
      imaging (CeMRI) in patients with myocardial infarction (MI). METHODS: There were
      twenty-three patients enrolled in this study. After dynamic observation, there
      were 20 patients who were diagnosed as MI. All those patients underwent coronary
      artery angiography and CeMRI. MRI was performed with a 1.5-T magnet (AVANTO,
      SIMENS). After tagged images were acquired, the patients received an intravenous
      bolus of 0.1 mmol/kg Gd-DTPA at a rate of 5 ml/s. A first-pass perfusion scan was
      acquired simultaneously with a bolus injection. A second bolus of 0.3 mmol/kg Gd
      DTPA was given following the first-pass images. Delayed images were acquired 5
      minutes after the second bolus by using an inversion-recovery prepared gated fast
      gradient echo-pulse sequence. RESULTS: Hypoenhancement was seen in 20 patients at
      the first-pass perfusion at the myocardial infarction site, while
      hyperenhancement was seen at delayed CeMRI. Myocardial infarction area in delayed
      CeMRI was 16.58% +/- 9.73%, which was correlated positively with peak CK and cTnT
      (r = 0.821, P < 0.01 and r = 0.565, P < 0.05), respectively. The ejection
      fraction (EF) detected by MRI was 0.46 +/- 0.13, while the left ventricular EF
      (LVEF) detected by left ventriculography was 0.49 +/- 0.16. There was no
      difference between two parameters. CONCLUSIONS: CeMRI may play an important role
      in the diagnosis and prognosis of patients with MI.

PMID- 16563256
TI  - [Growth and differentiation of adult canine autologous skeletal myoblasts after
      transplanted into acute myocardial infarction region].
AB  - OBJECTIVE: To study the growth and differentiation of adult canine autologous
      skeletal myoblasts after being transplanted into acute myocardial infarction
      (AMI) region by intramyocardium injection (IMI) and intracoronary infusion (ICI).
      METHODS: Autologous skeletal myoblasts were procured by a modified method. AMI
      model of adult canine was obtained through left anterior descending branch
      ligation and was divided into 4 groups (n = 5 for each group). Autologous
      skeletal myoblasts (1.0 - 1.4 x 10(8) cells) were injected locally into AMI
      region or infused into infarction-related coronary artery. Specimens were
      harvested 4 weeks after cellular transplantation for histological study including
      HE, PTH, immunochemical stain and transmission electronmicroscope. RESULTS: In
      both two transplantation groups, newborn muscle-derived cells, striated muscle
      tissue and mature skeletal myofibril were demonstrated existing in MI region by
      electronmicroscope, PTH stain or anti-skeletal myosin heavy chain (slow)
      immunochemical stain, respectively. Newborn striated muscle tissues arranged in
      order of consistency with host myocardial fibers in two treatment groups. Newborn
      striated muscle tissue was more inclined to gather in MI region in the local
      injection group but distracted from each other in the intracoronary infusion
      group. CONCLUSION: Autologous skeletal myoblasts appears to live and
      differentiate into mature striated muscle tissue after transplanting into AMI
      region by IMI or ICI routes.

PMID- 16563257
TI  - [Na+-H+ exchanger protein changes in vascular smooth muscle and effect of Na+-H+
      exchange inhibitor on vessel stenosis after balloon injuries in rabbits].
AB  - OBJECTIVE: To explore the mechanism and effect of sodium/hydrogen exchanger
      (Na(+)-H(+) exchanger, NHE), amiloride, on vessel stenosis. METHODS: Thirty-two
      adult male New Zealand white rabbits were randomly divided into groups of
      amiloride intervention (IG, n = 12), balloon injury (BG, n = 10) and sham
      operation (SG, n = 10). A 2.5 mm x 20 mm Foley's tube was used to injury left
      side iliac artery in the IG and BG groups, whereas a same Foley's tube was
      inserted into the vessel without any injuries in the SG group. Amiloride (5
      mg.kg(-1).d(-1)) was intraperitoneally injected 3 days before balloon injuries
      and the same dosage normal saline was used in the same way in the BG group for 28
      days after operation. The rabbits were killed and the iliac arteries were stained
      with Hematoxylin-Eosin, alpha-actin and Masson's trichrome to observe the
      morphologic changes in the vessel cava, neointima, media layer, and vascular
      smooth muscle cells (VSMCs) migration into the neointima and extracellular
      matrixes (ECMs). RESULTS: Four weeks after balloon injuries in rabbits, a cave
      narrow of the iliac artery and neointima were found and the media layer (VSM
      layer) was proliferated. The quantities of NHE-1 protein from artery smooth
      muscle in all the groups were 0.21 +/- 0.02, 0.25 +/- 0.04 and 0.11 +/- 0.03 (P <
      0.01), respectively. The difference between the BG and SG groups was significant,
      which indicated that the NHE-1 proteins increased after balloon injury. The
      quantities of NHE-1 protein from the IG group were lower than those from the BG
      group. The cave areas were 0.91 mm(2) +/- 0.23 mm(2), 0.68 mm(2) +/- 0.19 mm(2)
      and 1.08 mm(2) +/- 0.17 mm(2) (P < 0.01), respectively. The intima areas were
      0.27 mm(2) +/- 0.15 mm(2), 0.67 mm(2) +/- 0.24 mm(2) and 0.05 mm(2) +/- 0.03
      mm(2), respectively (P < 0.01). The ratios of intima to media area were 1.21 +/-
      0.24, 1.39 +/- 0.26 and 0.15 +/- 0.08 (P < 0.01), respectively. Amiloride
      increased vessel cave areas, but decreased intima areas and intima to media
      ratios in the IG group. In the IG group, alpha-actin positive areas in neointima
      was higher (16,328.31 microm(2) +/- 6220.27 microm(2)) than those in the SG group
      (4164.15 microm(2) +/- 1788.37 microm(2)) (P < 0.01). ECMs areas in neointima in
      the IG group were lower (8910.62 microm(2) +/- 7041.62 microm(2)) than those in
      the SG group (33,358.76 microm(2) +/- 7290.17 microm(2)) (P < 0.01). CONCLUSIONS:
      Balloon injuries of iliac artery in rabbits induce VSMCs proliferation,
      migration, narrowed cave and vessel stenosis. Amiloride, a NHE-1 inhibitor, may
      relieve this vessel stenosis.

PMID- 16563268
TI  - [RNAi and its application for treatment of cardiovascular diseases].

PMID- 16563270
TI  - [The biological treatment of heart failure: current status and prospect].

PMID- 16563272
TI  - [The relationship between the beta-2-adrenergic receptor gene +46 Arg 16/Gly
      variant and serum level of low density lipoprotein-cholesterol in Kazakans of
      Xinjiang].
AB  - OBJECTIVE: To investigate the distribution of beta-2-AR +46 A-->G variant in
      Kazakans of Xinjiang and the relationship of the variant with low density
      lipoprotein-cholesterol (LDL-C) level in this population. METHODS: The genotypes
      of beta-2-AR gene Arg16/Gly variant were detected by the polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) technique in 506
      Kazakans with age from 30 to 69, and its distribution and relationship to LDL-C
      level were investigated. RESULTS: (1) The frequencies of genotypes AA, AG, GG and
      alleles A, G of beta-2-AR +46 variant in this population were 0.310, 0.455, 0.235
      and 0.538, 0.462 respectively, which were accorded with Hardy-Weinberg
      equilibrium. (2) The Gly16/Gly genotype had highest LDL-C level in the three
      genotypes, and were significantly higher than Arg16/Gly genotype (P < 0.05). (3)
      Comparing the effect of beta-2-AR gene +46 variant on serum lipid in males with
      females, we found that females with Gly16/Gly genotype had the highest level of
      serum LDL-C. CONCLUSIONS: These data show that Gly16/Gly genotype of beta-2-AR
      gene +46 A-->G variant is associated with higher level of serum LDL-C in this
      population, especially in female.

PMID- 16563271
TI  - [China coronary secondary prevention study (CCSPS): outcomes from analysis of
      coronary heart disease patients with diabetes].
AB  - OBJECTIVE: To elucidate whether lipid-lowering therapy with Xuezhikang can induce
      a decrease of cardiac events and an attenuation of total mortality in coronary
      heart disease (CHD) patients with diabetes. METHODS: We designed a random, double
      blinded, placebo controlled clinical trial in selected 591 patients. All patients
      were administrated with capsule Xuezhikang (0.6 g, Bid) or placebo in addition to
      conventional therapy. The mean follow-up period was four years. The primary end
      points were nonfatal myocardial infarction and death from CHD. RESULTS: (1) The
      incidence of CHD events and that of death from CHD were reduced by 50.8% (P =
      0.0008) and by 44.1% (P = 0.0246) in treatment group, respectively; Also, the
      incidence of nonfatal myocardial infarction was reduced by 63.8% (P = 0.0151).
      (2) The incidence of stroke, tumor, and PCI/CABG were decreased by 20.2%. (3) The
      total mortality were lowered by 44.1% in treatment group (P = 0.0097).
      CONCLUSION: Xuezhikang can effectively reduce the incidence of cardiac events and
      total mortality in CHD patients with diabetes.

PMID- 16563273
TI  - [The effect of atorvastatin on the expression of CD55, CD59 in patients with
      hyperlipidemia].
AB  - OBJECTIVE: To study the expressions of CD55 and CD59 in patients with
      hyperlipidemia and the effects of atorvastatin on it, and to identify the
      possible influential factors. METHODS: We selected 67 patients with
      hyperlipidemia, and 24 healthy people matched in terms of age, sex and body
      weight as control. The expressions of CD55 and CD59 on white blood cells were
      detected by flow cytometry, and their relationships to blood lipids, complement
      activation indexes (C(5a), sC(5b-9)), inflammatory factors (high sensitivity C
      reactive protein (hsCRP), TNF-alpha, IL-6 were analyzed. 24 patients with
      hyperlipidemia were treated with atorvastatin for 8-12 weeks and the expressions
      of CD55 and CD59 were measured before and after atorvastatin therapy. RESULTS:
      The mean fluorescence intensity (MFI) of CD55 lymphocytes and monocytes were
      decreased in patients with hyperlipidemia compared with control (2.07 +/- 0.28 vs
      2.29 +/- 0.44 and 3.45 +/- 1.02 vs 4.33 +/- 2.32, P < 0.01 and P < 0.05,
      respectively). CD55 positive lymphocyte MFI was negatively correlated with waist
      circumference, waist-hip ratio, hsCRP and C(5a). C(5a) was negatively correlated
      with the MFIs of CD55 positive lymphocytes, monocytes, granulocytes, and
      positively with TG and diastolic blood pressure. After atorvastatin therapy, the
      MFIs of CD59 positive lymphocytes, monocytes and granulocytes increased (4.34 +/-
      1.16 vs 3.69 +/- 0.76, 4.52 +/- 1.36 vs 3.91 +/- 0.89, 5.67 +/- 1.72 vs 4.56 +/-
      1.03, P < 0.05, < 0.05 and < 0.01 respectively), which were not correlated with
      changes of blood lipids. CONCLUSIONS: The expression of CD55 is down-regulated in
      hyperlipidemia, which might be influenced by obesity, abdominal distribution of
      adipose tissue and inflammatory status of hyperlipidemia, but not by blood
      lipids. The expression of CD55 is related with complement activation; The
      expression of CD59 is up-regulated after atorvastatin treatment independently of
      blood lipids.

PMID- 16563274
TI  - [Atorvastatin upregulates the expression of PPAR alpha/gamma and inhibits the
      hypertrophy of cardiac myocytes in vitro].
AB  - OBJECTIVE: To investigate the effects of atorvastatin on angiotensin II (Ang II)
      induced hypertrophy of cardiac myocytes (MC) and the changes of mRNA expression
      of peroxisome proliferators-activated receptor alpha, gamma (PPAR alpha, gamma)
      subtypes in vitro. METHODS: Hypertrophy in neonatal rat MC was established with
      Ang II and treated with atorvastatin. The surface area of MC was analyzed by the
      aid of NIH Image J software, and the synthetic rate of protein in MC was detected
      by (3)H-leucine incorporation. mRNA expression of atrial natriuretic peptide
      (ANP), brain natriuretic peptide (BNP), matrix metalloproteinase (MMP) 9, MMP2,
      interleukin1beta (IL-1beta) and PPARalpha, gamma was measured by reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Changes of MC were
      detected induced by Ang II, including increases in surface area, mRNA expression
      of ANP, BNP, MMP9, MMP2 and IL-1beta, and (3)H-leucine incorporation, as well as
      a decrease in mRNA expression of PPARalpha, gamma. Treatment with atorvastatin
      inhibited the changes above in a dose-dependent manner, but no change was found
      in treated with DMSO. CONCLUSION: Atorvastatin inhibits cardiac hypertrophy in
      vitro. It is suggested that atorvastatin has a potential role in the prevention
      and treatment of cardiac diseases such as cardiac hypertrophy, and PPAR alpha and
      gamma maybe involved in this process.

PMID- 16563276
TI  - [The changes and impact factors of carotid-femoral and carotid-radial pulse wave
      velocity in patients with essential hypertension].
AB  - OBJECTIVE: To analyze the changes of carotid-femoral and carotid-radial pulse
      wave velocity in patients with essential hypertension, and effects of age and
      levels blood pressure levels on these changes. METHODS: Automatic pulse wave
      velocity (PWV) measuring system was applied to examine carotid-femoral PWV
      (CFPWV) and carotid-radial PWV (CRPWV) as the parameters reflecting central
      elastic large arterial and peripheral muscular medium-sized arterial elasticity
      respectively. 517 hypertensive patients aged 17-82 years (272 males and 245
      females, mean age 52.0 +/- 13.0 years) and 118 healthy subjects aged 19-82 years
      (52 males and 66 females, mean age 54.2 +/- 13.8 years) were recruited in the
      study. RESULTS: CFPWV increased with age in both groups (P < 0.001), whereas
      CRPWV did not change significantly. CFPWV and CRPWV both increased with blood
      pressure. A stepwise multiple regression analysis demonstrated that age and
      systolic blood pressure were positively related to CFPWV independently, while
      diastolic blood pressure was significantly associated with CRPWV. CONCLUSIONS:
      Age and components of blood pressure exert different effects on elasticity of
      central elastic large artery and peripheral muscular medium-sized artery.
      Examining the change of large arterial elasticity has important clinical value in
      hypertensive patients.

PMID- 16563277
TI  - [Management of the arrhythmia around the procedure of transcatheter closure of
      ventricular septal defects in pediatric patients].
AB  - OBJECTIVE: To discuss the treatment of arrhythmia occurs in the process of
      transcatheter closure of perimembranous ventricular septal defects (VSD) in
      pediatric patients. METHODS: 182 cases (mean age: 6.2 +/- 3.3 years) with
      membranous VSD underwent transcatheter occlusion procedure. Two different devices
      were used: the Amplatzer membranous VSD occluder in 81 patients and the domestic
      made device in 101 patients. Electrocardiogram of all patients was recorded
      before and during closure and at one day after the procedure, and Holter
      monitoring was performed one week after the procedure. RESULTS: Perioperation
      arrhythmia occurred in thirty-one patients (17%). Second- or third-degree
      atrioventricular bundle (AVB) was noted during the procedure in four patients.
      Normal AV conduction recovered spontaneously before the catheters were withdrawn
      in three cases and another patient underwent surgical repair. In the other twenty
      seven patients, arrhythmia was first documented between one day and one week
      after the procedure. Third-degree AVB was found in three (1.6%) children after
      the procedure and underwent the temporary pacemaker (TPM) was implanted, two of
      them recovered to normal sinus rhythm within one week, another patient underwent
      elective surgery to remove the occluder and repair the defect. Other arrhythmias
      were: left bundle-branch block (n = 3), right bundle-branch block (n = 12),
      second-degree AVB (n = 2), sinus tachycardia (n = 6). CONCLUSIONS: In properly
      selected cases of perimembranous VSD, the transcatheter closure is safe and
      effective by using appropriate devices. During and after the procedure, closure
      of VSD can be associated with some kinds of arrhythmia, such as A-V block, more
      intensive observation and follow-up were therefore needed.

PMID- 16563278
TI  - [Comparison of pulmonary perfusion imaging with pulmonary angiography in
      diagnosis of pulmonary involvement in Takayasu's arteritis].
AB  - OBJECTIVE: To compare the diagnostic value of (99)Tc(m)-MAA pulmonary perfusion
      imaging with that of pulmonary angiography for pulmonary involvement in
      Takayasu's arteritis. METHODS: Twenty-one patients (19 women, 2 men), with
      diagnosed Takayasu's arteritis and underwent both (99)Tc(m)-MAA pulmonary
      perfusion imaging and pulmonary angiography, were retrospectively analyzed.
      RESULTS: Out of the 21 patients, pulmonary angiography detected 11 patients with
      pulmonary artery involvement whereas 13 patients were revealed perfusion defects
      by pulmonary perfusion imaging. The agreement of diagnosis by pulmonary perfusion
      imaging with that by pulmonary angiography existed in 19 patients (90.5%, Kappa =
      0.81, P < 0.0001). There were 331 pulmonary segments consistently diagnosed by
      pulmonary perfusion imaging and pulmonary angiography in 378 pulmonary segments
      (87.5%, Kappa = 0.74, P < 0.0001). CONCLUSIONS: Pulmonary perfusion imaging is
      highly accorded with pulmonary angiography in detecting the pulmonary involvement
      in Takayasu's arteritis. Therefore, pulmonary perfusion imaging could be used as
      a non-invasive screening test for the pulmonary artery involvement in Takayasu's
      arteritis.

PMID- 16563279
TI  - [The safety and efficacy of Cypher drug-eluting stent: results from a six months
      follow-up study in patients with ST-segment elevation myocardial infarction].
AB  - OBJECTIVE: To investigate the feasibility, safety and efficacy of Cypher drug
      eluting stent implanted after the emergency percutaneous coronary intervention
      (PCI) in patients with ST-segment elevation myocardial infarction (STEMI).
      METHODS: From Nov. 2002 to Dec. 2004, 186 patients with STEMI treated by
      emergency PCI were included into this study. The incidence of major adverse
      cardiovascular event (MACE), stent thrombosis and restenosis were evaluated
      during 6 months follow-up after PCI. RESULTS: One hundred and sixty-eight
      patients were successfully treated by emergency PCI and there were no
      complication during the procedure. The rates of successful treatment were 100%.
      One hundred and seventy-five Cypher drug-eluting stents were successfully
      implanted into 171 target lesions. There was one case with acute stent thrombosis
      among 186 patients, and the MACE and mortality were 2.4% and 1.8%, respectively,
      during the first one month follow up. Six months later, the MACE was 4.2% and the
      mortality was 2.4%. The in-stent thrombosis and restenosis rates were 1.2% and
      1.8%, respectively, when evaluated by angiography and clinic follow up at six
      months after PCI. CONCLUSION: Implanting a Cypher drug-eluting stent in STEMI
      patients during emergency PCI is as safe and effective as a conventional bare
      stent. Cypher drug-eluting stent can reduce restenosis rate and MACE in STEMI
      patients treated with emergency PCI.

PMID- 16563280
TI  - [A randomized clinical trial on comparison of weight-adjusted dose with low dose
      recombinant tissue-type plasminogen activator on Chinese patients with acute
      myocardial infarction].
AB  - OBJECTIVE: The aim of the study was to quest appropriate dose of recombinant
      tissue-type plasminogen activator (rt-PA) on Chinese patients with acute
      myocardial infarction. METHODS: All enrolled patients were randomized into weight
      adjusted dose or low dose rt-PA group, and received a basal treatment with
      aspirin and heparin. Additionally, after an intravenous bolus of 8 mg rt-PA,
      patients in weight-adjusted dose group (n = 93) were given an intravenous
      infusion of 42-92 mg rt-PA (1 mg/kg body weight), while patients in the low dose
      group (n = 91) were treated with an intravenous infusion of 42 mg rt-PA over 90
      minutes. The observational endpoint included reperfusion rate of the infarct
      related artery by clinical criteria, left ventricular ejection fraction and major
      adverse cardiovascular events within 30 days in the two groups. RESULTS: There
      were 74 patients diagnosed reperfusion by clinical criteria in weight-adjusted
      dose group and 59 patients in low dose group (79.6% vs 64.8%, P = 0.026). The
      left ventricular ejection fraction seemed to be better in weight-adjusted dose
      group than in low dose group (P = 0.259). The major adverse cardiovascular events
      within 30 days were less in weight-adjusted dose group than in low dose group (P
      < 0.05). CONCLUSION: There was statistical significant superiority of weight
      adjusted dose over low dose rt-PA in the treatment of Chinese patients with acute
      myocardial infarction.

PMID- 16563281
TI  - [Changes of neutrophil myeloperoxidase in coronary circulation among patients
      with acute coronary syndrome].
AB  - OBJECTIVE: To investigate the changes of neutrophil myeloperoxidase (MPO) blood
      concentration gradient between the systemic circulation and the coronary
      circulation among patients with acute coronary syndrome and its clinical value.
      METHODS: Fifty patients underwent coronary angiography, which including 10
      patients in AMI group, 20 patients in UA group, 10 patients in SA group and 10
      subjects served as control. The levels of MPO and hs-CRP were measured in the
      serum of blood collected from femoral vein, aortic artery root and coronary
      sinus. RESULTS: Compared with the control, concentrations of LDL in the AMI, UA
      and SA groups were significantly increased, while the latter three groups did not
      differ from each other. In the UA patients, the in-gate percentage of MPO
      decreased in the coronary sinus compared with that in the root of aortic artery
      (P < 0.01); the in-gate percentage of MPO decreased through coronary circulation
      more than through systemic circulation (P < 0.001); the average fluorescent
      intensity of MPO and the concentrations of hs-CRP showed no difference between
      samples from the coronary sinus and that from the root of aortic artery. In the
      AMI patients, the average fluorescent intensity of MPO in the coronary sinus was
      weakened compared with that in the root of aortic artery (P < 0.05); it decreased
      through coronary circulation more than through systemic circulation (P < 0.001);
      neither the in-gate percentage of MPO nor the concentrations of hs-CRP showed
      significant difference between samples from the coronary sinus and that from the
      root of aortic artery. In the control and SA groups, samples from the femoral
      vein, the root of aortic artery, and the coronary sinus did not show differences
      at the serum level of MPO and hs-CRP. In the UA group, the in-gate percentage of
      MPO correlated positively with the concentration of hs-CRP (r = 0.78, P < 0.01),
      and with the level of LDL as well (r = 0.52, P < 0.05); In the AMI group, the
      average fluorescent intensity of MPO correlated negatively with the concentration
      of hs-CRP (r = -0.80, P < 0.01), and showed no correlation with the level of LDL
      (r = 0.22, P > 0.05). CONCLUSIONS: MPO is a better marker for inflammation of the
      local plaques. It may be one of the mechanisms that MPO induces the transforming
      from LDL to ox-LDL in plaques vulnerability.

PMID- 16563282
TI  - [Tissue Doppler imaging evaluate the effect of optimal biventricular
      resynchronization for congestive heart disease in left ventricular synchrony and
      function].
AB  - OBJECTIVE: To evaluate the immediate change of left ventricular systolic
      performance and asynchronization between simultaneous biventricular pacing and
      sequential biventricular pacing by tissue synchronization imaging (TSI) and
      tissue velocity imaging (TVI) in patients with congestive heart failure. The
      effect of sequential biventricular resynchronization therapy was also observed.
      METHODS: Ten patients with dilated cardiomyopathy who received sequential
      biventricular resynchronization were enrolled. The TVI and TSI imagings were
      performed by GE vivid7 with M3S probe. The left ventricular ejection fraction
      (LVEF), stroke volume (SV), aortic velocity time integral (VTI), left ventricular
      end diastolic diameter (LVEDd), the standard deviation of the electro-mechanical
      delay (EMD-SD) of 6 segments and TSI index were measured before implanting of
      InSync 8042 and 1 month, 3 months, 6 months after implanting respectively.
      RESULTS: After 6 months of implanting, the LVEF, SV and VTI were obviously
      increased from (22.0 +/- 8.8)% to (38.0 +/- 9.9)%; (36.0 +/- 14.9) ml to (57.0 +/
      15.7) ml; (20.22 +/- 5.72) cm to (26.20 +/- 5.98) cm, P < 0.05, respectively,
      compared with the before of implanting. The LVEDd was decreased from (6.6 +/-
      0.6) cm, to (6.0 +/- 0.9) cm, P < 0.05. The EMD-SD and TSI-index were declined
      gradually after implanting, which was more evident in the 6 months after
      implanting, from (83.07 +/- 46.99) ms to (22.37 +/- 16.38) ms; (2.20 +/- 0.36) to
      (1.50 +/- 0.43), P < 0.05, respectively, but the immediate EMD-SD did not change
      obviously between simultaneous biventricular pacing and sequential biventricular
      pacing, whereas, the TSI index and VTI were significantly improved from (1.87 +/-
      0.31) to (1.71 +/- 0.29); (22.44 +/- 5.43) cm to (25.44 +/- 5.36) cm, P < 0.05,
      respectively, in the sequential biventricular pacing. CONCLUSION: Sequential
      biventricular resynchronization could improve the left ventricular systolic
      function and synchronism of wall motion in the patients with congestive heart
      failure, which is more effective than simultaneous biventricular pacing after
      implanting immediately.

PMID- 16563283
TI  - [Distribution and property of anti-beta3-adrenoceptor autoantibody in patients
      with heart failure].
AB  - OBJECTIVE: To investigate the biological effects of anti-beta(3) adrenoceptor
      (beta(3)-AR) autoantibody in the serum of patients with heart failure, which may
      contribute to a new therapeutic clue for heart failure. METHODS: The synthetic
      peptide of the second extracellular loop of the beta(3)-AR was used as the
      antigen to screen sera of patients with heart failure and of healthy controls by
      using enzyme-linked immunosorbent assay. IgG in the patients group of positive
      autoantibody sera was prepared by using a MabTrap Kit (Amersham) following the
      manufacturer's instructions. The effects of IgG per each group both on
      contractile response of adult isolated cardiomyocytes and on beating frequency of
      cultured neonatal rat cardiomyocytes were observed. RESULTS: The positive rate of
      anti-beta(3)-AR autoantibody was 26.7% (mean antibody titer: 1:43.27 +/- 2.71) or
      11.0% (mean antibody titer: 1:14.59 +/- 1.61) in patients or healthy subjects,
      respectively P < 0.05. Compared with the control group, the autoantibody against
      beta(3)-AR from the patients group decreased cell shortening amplitude/cell
      shortening 3.84% +/- 0.33%, the velocity of shortening -0.47 microm/s +/- 0.07
      microm/s and relengthening 0.17 microm/s +/- 0.02 microm/s in adult isolated
      cardiac myocytes, respectively. The autoantibody in the patients group decreased
      the beating rate in cultured neonatal rat cardiac myocytes by 47.1 beats/min +/-
      8.11 beats/min, which could have a 6-hour continuance. This decreasing was not
      modified by Nadolol (beta(1)-AR and beta(2)-AR antagonist) in pretreating
      myocytes, but was nearly prevented by Bupranolol (nonselective beta-AR
      antagonist) or beta(3)-AR specific antigen. CONCLUSION: It seems reasonable to
      state that a high titer of the autoantibody against beta(3)-AR in the serum in
      patients with heart failure, which could have a negative inotropic and
      chronotropic effect, may be a part of pathophysiological mechanisms of heart
      failure.

PMID- 16563285
TI  - [Arachidonic acid epoxygenases and their metabolites promote angiogenesis].
AB  - OBJECTIVE: To investigate the angiogenetic effects of endogenous and exogenous
      epoxyeicosatrienoic acids (EET) and the relevant signaling mechanisms involved.
      METHODS: Bovine aortic endothelial cells (BAEC) were incubated with synthetic
      EETs or infected with recombinant adeno-associated viruses (rAAV) containing
      CYP2C11-CYPOR, CYP2J2 or CYP102 F87V mutant to increase endogenous expression
      levels of EETs. BAEC proliferation measured by cell counting and chromatometry,
      migration assessed by transwell analysis, and capillary formation determined by
      chicken embryo chorioallantoic membrane assays (CAM) and tube formation tests on
      matrigel and angiogenesis were analysed in vivo. The potential involvement of
      various signaling pathways were explored using selective inhibitors. RESULTS:
      Transfection with rAAV-2C11OR, rAAV-2J2 or rAAV-F87V promoted BAEC proliferation,
      migration, and capillary tubule formation. However, the effects of EETs on
      proliferation, migration and capillary tubule formation were attenuated by
      inhibitors of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3
      kinase (PI3 kinase)/Akt pathways, and partially attenuated by endothelial nitric
      oxide synthase (eNOS) inhibitor, but not by a protein kinase C inhibitor. In a
      rat ischemic hind limb model, rAAV-mediated epoxygenase transfection induced
      angiogenesis. CONCLUSIONS: Arachidonic acid epoxygenase and its metabolites can
      promote angiogenesis through activating MAPK and PI3 kinase/Akt signaling
      pathways, and to some extent, the eNOS pathway, and the angiogenic effects may
      provide protection to ischemic tissues.

PMID- 16563286
TI  - [Hypertension in D3 dopamine receptor deficient mice].
AB  - OBJECTIVE: To investigate the mechanisms by which hypertension occurs in D(3)
      dopamine receptor null mice (D(3)-/-). METHODS: Several parameters, including
      blood pressure, renal sodium excretion, D(3) receptor protein and mRNA
      expression, plasma renin activity, norepinephrine concentration and AT(1)
      receptor expression were checked in D(3)-/- mice and their littermate wild type
      mice (D(3)+/+). Moreover, the vasorelaxant effect of D(3) receptor stimulation
      was measured with ex-vivo mesenteric artery isolated from Wistar-Kyoto rats.
      RESULTS: Blood pressure was higher in D(3)-/- mice compared with that in D(3)+/+
      mice, salt-loading had no effect on blood pressure in both groups, at the last
      period, sodium excretion was lower in D(3)-/- mice as compared with D(3)+/+ mice,
      renal renin activity and AT(1) receptor expression were higher in D(3) -/-
      [corrected] mice than in D(3) +/+ [corrected] mice. In contrast, no difference of
      renal norepinephrine was found in two groups. When using angiotensin II subtype-1
      receptor antagonist, the systolic blood pressure declined for a longer duration
      in mutant mice than in wild-type mice. Vaso-relaxation was found in ex-vivo
      isolated mesenteric artery when D(3) receptor was stimulated. CONCLUSIONS:
      Elevation of blood pressure in D(3)-/- mice might be related with impaired renal
      sodium excretion and vaso-relaxation in resistance artery.

PMID- 16563288
TI  - [Tumor necrosis factor-alpha induces release of endothelial microparticles from
      human endothelial cells].
AB  - OBJECTIVE: The present study was designed to investigate whether Tumor necrosis
      factor (TNF)-alpha stimulates release of endothelial microparticles (EMPs) by
      human endothelial cells, and whether EMPs may serve as a promising marker for
      endothelial injury and dysfunction. METHODS: Human umbilical venous endothelial
      cells (HUVEC) were incubated with or without TNF-alpha for 24 hours at 37 degrees
      C. EMPs generated on the surface of HUVEC were observed with a scanning electron
      microscopy. The CD31 and CD51 positive EMPs in culture supernatants were measured
      by flow cytometer. RESULTS: Fewer vesicles were observed on cell surface of
      control group, in TNF-alpha-stimulated one, however, cells manifested a blebby
      surface (eruption phenomenon) and more vesicles on surface were observed. The
      levels of EMPs were significantly increased in TNF-alpha stimulated cells
      compared with controls [CD31 + EMP, (164 +/- 63)/1000 cells vs. (42 +/- 10)/1000
      cells, P < 0.05; CD51 + EMP, (260 +/- 108)/1000 cells vs. (19 +/- 4)/1000 cells,
      P < 0.05]. CONCLUSION: TNF-alpha can stimulate HUVEC to release EMPs which may
      serve as a surrogate marker for endothelial injury and dysfunction.

PMID- 16563290
TI  - [Effects and the mechanism of carvedilol on gap junctional intercellular
      communication in rat myocardium].
AB  - OBJECTIVE: To examine the effects of carvedilol on myocardial ischemia and
      reperfusion injury and on gap junctional intercellular communication (GJIC).
      METHODS: The left coronary artery was occluded for 30 min and reperfused for 4 h.
      The activity of creatine phosphokinase (CK), lactate dehydrogenase (LDH) and the
      infarct size were measured. Isolated buffer-perfused hearts were divided randomly
      into four groups, sham operation (SO), myocardial ischemia and reperfusion (IR),
      carvedilol (CV) and heptanol (a gap junctional inhibitor) (HT). The effect of
      carvedilol on GJIC was measured by a modification of Scrape-loading and dye
      transfer method, and the state of CX43 phosphorylation was evaluated by Western
      blot. RESULTS: Compared with the SO group, Increased CK, LDH and infarct size
      were found in the IR group after 4 h reperfusion. GJIC in the IR group was not
      inhibited, but dephosphorylated CX43 was increased after 30 minutes of ischemia.
      Carvedilol decreased CK, LDH and infarct size compared with the IR rats; after 30
      minutes of ischemia, both carvedilol and heptanol significantly reduced the GJIC,
      associated with a significant augmentation of dephosphorylated CX43. CONCLUSIONS:
      These results suggest that carvedilol reduces GJIC during ischemia presumably by
      dephosphorylating Cx43, which may be one of the mechanisms of lessening
      myocardial ischemia-reperfusion injury.

PMID- 16563296
TI  - [Transient left ventricular apical ballooning syndrome].

PMID- 16563298
TI  - Faster, better, cheaper: lean labs are the key to future survival.
AB  - Process improvement techniques have been used in manufacturing for many years to
      rein in costs and improve quality. Health care is now grappling with similar
      challenges. The Department of Laboratory Services at Good Samaritan Hospital, a
      560-bed facility in Dayton, OH, used the Lean process improvement method in a 12
      week project to streamline its core laboratory processes. By analyzing the flow
      of samples through the system and identifying value-added and non-value-added
      steps, both in the laboratory and during the collection process, Good Samaritan's
      project team redesigned systems and reconfigured the core laboratory layout to
      trim collection-to-results time from 65 minutes to 40 minutes. As a result,
      virtually all morning results are available to physicians by 7 a.m., critical
      values are called to nursing units within 30 minutes, and core laboratory
      services are optimally staffed for maximum cost-effectiveness.

PMID- 16563299
TI  - Turnaround time improvement and department-wide benefits of automation in
      urinalysis.
AB  - A retrospective study was done pre- and post-implementation of the iQ200
      Automated Urinalysis System (composed of the iQ200 Automated Urine Microscopy
      Analyzer and the Arkray AUTION MAX AX-4280, Iris Diagnostics) to evaluate its
      impact on process improvement. Routinely-collected turnaround time (TAT) data was
      evaluated. While some pre-analytical steps were reassigned to non-technical staff
      post-implementation to better match skills to tasks, a considerable improvement
      in TAT was seen. TAT was measured as time from "order to result" and noted as the
      percentage of reports available at 30, 45, and 60 minutes. Post-implementation
      improvements for urinalysis showed a 30 percent increase in availability of
      reports at 30 minutes, 9 percent improvement at 45 minutes, and 3.2 percent
      improvement at 60 minutes. The urinalysis staff also handled hematology duties.
      Post-implementation, a 44 percent improvement for CBCs was noted in the 30-minute
      TAT, 22 percent improvement at 45 minutes, and 8 percent improvement at 60
      minutes. Laboratory staff were able to complete urinalysis testing more quickly
      and therefore attend to CBCs sooner, resulting in improved TAT for both tests.
      These improvements were sustained for at least seven months post-implementation.

PMID- 16563300
TI  - Improvements to the CAP Laboratory Accreditation Program.

PMID- 16563301
TI  - A culture of quality: inspection readiness.

PMID- 16563302
TI  - Laboratory accreditation 101.

PMID- 16563303
TI  - Thinking about the unthinkable: are we really prepared for impending disaster?

PMID- 16563304
TI  - A potential time bomb.

PMID- 16563306
TI  - PTSD in victims of sexual assault: test of a major component of the Ehlers-Clark
      theory.
AB  - We investigated a major component of the Ehlers-Clark theory of post-traumatic
      stress disorder (PTSD) in a sample of 50 female victims of sexual assault. In
      particular, we tested the hypothesis that the victims' appraisals of the trauma
      and its consequences contribute significantly to the persistence of PTSD
      symptoms. The results indicated that the victims' appraisals of the sexual
      assault and its sequelae are strongly and positively related to PTSD symptoms.
      This finding remained significant after statistically controlling for the
      perceived severity of the assault. Most of the results are consistent with the
      Ehlers-Clark theory.

PMID- 16563307
TI  - The effects of continuous and partial reward on the vigilance task performance of
      adults with attentional deficits: a pilot investigation.
AB  - The effects of reward schedule (100% and 30%) and extinction on attention
      (reaction time to auditory stimuli) and frustration levels (pressure exerted on a
      response key) of 15 adults with attentional disorders and 21 normal adults were
      examined using a continuous performance task. We predicted, that adults with
      attentional deficits would (a) perform similar to comparisons when rewarded on a
      continuous schedule, (b) exhibit higher levels of frustration when that
      continuous schedule was moved to an extinction schedule, and (c) experience more
      frustration than comparisons when rewarded on a partial schedule. Overall, adults
      with attentional deficits were slower to respond and their responses were more
      variable than typical comparisons across trials, similar to what is observed for
      children. Continuous reward resulted in poorer performance earlier in the reward
      phase and continued throughout an extinction phase. The frustration levels of
      adults with attentional deficits did not differ from comparisons across schedule
      conditions. Results are discussed in terms of the role of arousal in mediating
      responding to various schedules of reward.

PMID- 16563308
TI  - Mental representation of observable attributes in people with social phobia.
AB  - Cognitive models of social phobia stress the importance of a negatively biased
      mental representation of ones social performance and appearance in maintenance of
      the disorder. People with social phobia (N=57) and non-clinical controls (N=41)
      engaged in a public speech and also completed several measures of perceived
      attributes including speech performance, physical attractiveness, and personal
      performance ability in several interpersonal areas. Independent observers also
      rated participants' speech performance and physical attractiveness. Relative to
      observers' ratings, individuals with social phobia reported significantly lower
      quality of speech performance and physical attractiveness than did non-clinical
      individuals. People with social phobia also reported significantly lower
      perceived ability in other areas of performance and appearance. These data held
      even after statistically controlling for levels of depression.

PMID- 16563309
TI  - From dissociation to trauma? Individual differences in dissociation as predictor
      of 'trauma' perception.
AB  - In clinical literature, dissociative complaints are generally considered to be
      the result of traumatic experiences. However, it has been argued that
      dissociative complaints, in turn, may indulge over-reporting of traumatic
      experiences. Hence, correlations between dissociation and self-reported trauma
      may not only reflect the causal path from trauma to dissociation, but possibly
      also an increased trauma-item endorsement due to dissociation. To test the idea
      that dissociation fosters a positive response bias on trauma self-reports,
      participants completed a dissociation scale, and subsequently rated the perceived
      trauma of ambiguous stimuli. Results indicated that some dissociative complaints
      indeed predicted increased scores on the trauma ratings, while other
      manifestations of dissociation were negatively correlated with perceived trauma
      ratings. Hence, there is reason to argue that people differ in their readiness to
      perceive a situation as traumatic. However, the association between self-reported
      dissociation and the perception of 'trauma' is not quite clear-cut.

PMID- 16563310
TI  - Use of an abbreviated form of the Edmonton staging system in a hospice setting.

PMID- 16563311
TI  - Celiac disease: not all medications are contaminated with gliadin...

PMID- 16563312
TI  - Re: efficacy, safety, and ethical validity of palliative sedation therapy.

PMID- 16563314
TI  - Symptom priority and course of symptomatology in specialized palliative care.
AB  - The study aim was to explore which symptoms/problems cancer patients in
      palliative care consider most distressing, and to investigate how prioritization
      at first contact was associated with patient-assessed symptom intensity and
      change in intensity over time. Initially, 175 patients named and prioritized
      their five most distressing symptoms. Weekly, they completed the following self
      assessment questionnaires: European Organization for Research and Treatment of
      Cancer Quality of Life Questionnaire-C30, Edmonton Symptom Assessment System, and
      the Hospital Anxiety and Depression Scale. Initial symptom intensity scores and
      weekly changes were calculated and compared with prioritization of the same
      symptom. Pain, fatigue, physical function, appetite, nausea/vomiting, dyspnea,
      and depression were the symptoms most often prioritized. Priority was associated
      with initial scoring of pain, appetite, nausea/vomiting, dyspnea, constipation,
      depression, and anxiety, but not with fatigue, physical function, role function,
      or inactivity. Priority was associated with change in symptom intensity for pain,
      reduced appetite, nausea/vomiting, and constipation. Symptom prioritization may
      be a useful guide to choice of treatment as well as to longitudinal symptom
      evaluation.

PMID- 16563315
TI  - Validation of the Cancer Care Monitor items for physical symptoms and treatment
      side effects using expert oncology nurse evaluation.
AB  - The Cancer Care Monitor (CCM) is a tablet computer-based multidimensional measure
      of symptom burden and quality of life. This study examined individual item
      validity for 42 items measuring general physical symptoms and treatment side
      effects. Patients (40 females and 20 males) completed the CCM and a blinded nurse
      interview. In general, patient self-reported symptoms on the CCM corresponded
      well to nurse-verified evaluations. There was excellent agreement between the
      patient-reported CCM items and nurses' ratings on whether the symptom was present
      or absent and on the severity of a given symptom. Additionally, the results
      suggested that the majority of items had high sensitivity, specificity, positive
      predictive value, negative predictive value, and Youden's Index score. Taken
      together, the results suggest that the CCM can provide an efficient method for
      collecting information about symptom presence and symptom burden at the point of
      care.

PMID- 16563316
TI  - Measuring the psychosocial characteristics of family caregivers of palliative
      care patients: psychometric properties of nine self-report instruments.
AB  - Researchers and clinicians have experienced substantial difficulties locating
      measures that are suitable for use within palliative care settings. This article
      details the psychometric properties of nine instruments designed to assess the
      following psychosocial characteristics of family caregivers: competence, mastery,
      self-efficacy, burden, optimism, preparedness, social support, rewards, and
      mutuality. Results are based on the responses of 106 primary family caregivers
      caring for relatives dying of cancer. Principal components extraction with
      varimax rotation was used to explore the underlying structure of each measure.
      Following the exclusion of complex variables, suggested components for most
      measures comprised relatively homogenous items, which were good to excellent
      measures of each component. Some components comprised only two items; however,
      Cronbach's alphas typically indicated moderate to high levels of internal
      consistency. Overall, the results of this study suggest that most of the measures
      analyzed, excepting the mastery and mutuality scales, can be recommended to
      examine the family caregiver experience and test supportive interventions.

PMID- 16563317
TI  - Giving meaning to measure: linking self-reported fatigue and function to
      performance of everyday activities.
AB  - Fatigue, a common symptom of cancer patients, particularly those on active
      treatment, is generally evaluated using self-report methods, yet it remains
      unclear how self-reported fatigue scores relate to performance of daily
      activities. This study examines the relationships among self-reported and
      performance-based measures of function in patients receiving chemotherapy (CT) to
      link self-reported fatigue measures to self-report and performance-based measures
      of function. Self-reported fatigue using the Functional Assessment of Chronic
      Illness Therapy-Fatigue (FACIT-F) and self-reported physical function using the
      physical function 10 subscale of the Short Form 36 (SF-36) (PF-10) were measured
      in 64 patients within 2 weeks of beginning CT (n=64) and after three cycles of CT
      (n=48). Motor and cognitive functions were captured using five self-reported and
      seven observed-performance measures at each time point. Significant correlations
      between self-reported and observed measures ranged from 0.30 to 0.71. Self
      reported fatigue correlated (0.30-0.45) with performance-based function. FACIT-F
      scores in the range of 30 and below and PF-10 scores in the range of 50 and below
      were related to an increased difficulty performing everyday activities. Observed
      measures of physical performance correlate moderately with self-reported fatigue
      and self-reported physical function. These relationships enable one to begin
      linking fatigue scores directly to a person's ability to perform everyday
      activities.

PMID- 16563318
TI  - Low morphine doses in opioid-naive cancer patients with pain.
AB  - Cancer pain can be managed in most patients through the use of the analgesic
      ladder proposed by the World Health Organization. Recent studies have proposed to
      skip the second "rung" of the ladder by using a so-called "strong" opioid for
      moderate pain. However, usual doses of strong opioids commonly prescribed for the
      third rung of the analgesic ladder may pose several problems in terms of
      tolerability in opioid-naive patients. The aim of this multicenter study was to
      evaluate the efficacy and tolerability of very low doses of morphine in advanced
      cancer patients no longer responsive to nonopioid analgesics. A sample of 110
      consecutive opioid-naive patients with moderate-to-severe pain were given oral
      morphine at a starting dose of 15 mg/day (10 mg in those older than 70 years).
      Doses were then titrated according to the clinical situation. Pain intensity,
      morphine doses, symptom intensity, quality of life, and the requirement for dose
      escalation were monitored for a period of 4 weeks. The treatment was effective
      and well tolerated by most patients, who were able to maintain relatively low
      doses for the subsequent weeks (mean dose 45 mg at Week 4). Only 12 patients
      dropped out due to poor response or other reasons. The use of very low doses of
      morphine proved to be a reliable method in titrating opioid-naive advanced cancer
      patients who were also able to maintain their dose, in a 4-week period, below the
      dose level commonly used when prescribing strong opioids.

PMID- 16563319
TI  - Institutionalizing effective pain management practices: practice change programs
      to improve the quality of pain management in small health care organizations.
AB  - The Resource Center of the American Alliance of Cancer Pain Initiatives provided
      templates, faculty, and ongoing consultation to assist seven state pain
      initiatives to implement programs to improve pain management practices. A total
      of 113 health care organizations participated. Each organization committed to
      support a team of two to three staff through a 10-month pain quality improvement
      process, which included a site visit, two educational conferences, pre- and
      postprogram analyses of the organizational structures in place to support pain
      assessment and management, quality improvement work plan development, and patient
      survey data collection. Postprogram results showed statistically significant
      increases in the presence of structural elements that are critical to effective
      pain management, as well as statistically significant, though modest, decreases
      in the percentage of patients who reported pain of any severity, and specifically
      moderate to severe pain, in the previous 24 hours. The largest changes occurred
      in long-term care facilities. Nevertheless, the percentage of patients in
      moderate to severe pain remained unacceptably high.

PMID- 16563320
TI  - Effects of a brief coping skills training intervention on nociceptive flexion
      reflex threshold in patients having osteoarthritic knee pain: a preliminary
      laboratory study of sex differences.
AB  - Studies have documented the efficacy of coping skills training (CST) for managing
      pain, distress, and disability in persons with arthritis. However, no laboratory
      studies have examined the effects of CST on descending modulation of nociception.
      This study used the nociceptive flexion reflex (NFR) to document pain and
      nociceptive responding among 62 men and women with osteoarthritis of the knee
      (mean age=63.3+/-7.5 years). Before and after a 45-minute CST session,
      participants completed laboratory assessments of NFR threshold and questionnaires
      evaluating pain and state anxiety. Results indicated significantly increased NFR
      thresholds and decreased pain ratings following CST for men and women. A
      significant time by sex interaction was observed for state anxiety, with women
      reporting greater decreases in anxiety following CST than men. This is the first
      study to demonstrate effects of a CST protocol on a measure of descending
      inhibition of nociception among patients with osteoarthritic knee pain.

PMID- 16563321
TI  - Palliative care program effectiveness research: developing rigor in sampling
      design, conduct, and reporting.
AB  - Research on palliative care presents some unique sampling challenges. The purpose
      of this paper is to articulate the sampling challenges that palliative care
      researchers face during phases of study design, conduct, and the reporting of
      results. Challenges include identifying a target population, avoiding selection
      bias in the face of clinician and patient denial of serious illness, developing
      eligibility criteria for a seriously ill population, minimizing high patient
      refusals due to illness, and accurate reporting of all screened and eligible
      participants. These challenges are explored within the context of a randomized
      clinical trial testing a palliative care intervention. Suggestions for improving
      scientific rigor in sampling design include 1) defining a target population that
      is consistent with research goals; 2) identifying eligibility criteria that are
      objective and understandable to clinicians to yield the desired sample; and 3)
      reporting results about the target population, sample eligibility/exclusions, and
      participation using standardized criteria.

PMID- 16563322
TI  - Anesthesiologists must do a better job of preventing operating room fires.

PMID- 16563323
TI  - Remifentanil pretreatment reduces myoclonus after etomidate.
AB  - STUDY OBJECTIVE: The aim of the study was to compare the effect of pretreatment
      with remifentanil 1 microg/kg and the effect of gender on the incidence of
      myoclonus after anesthesia induction with etomidate. DESIGN: This was a
      randomized, double-blind study. SETTING: The study was conducted at a university
      hospital. PATIENTS: Sixty patients were pretreated in a randomized double-blinded
      fashion with remifentanil 1 microg/kg or placebo. Two minutes after remifentanil
      or placebo injection, etomidate 0.3 mg/kg was given. MEASUREMENTS: Myoclonus was
      recorded with a scale of 0 to 3. The grade of sedation (none, mild, moderate,
      severe), nausea, pruritus, and apnea were recorded after injection of both drugs.
      MAIN RESULTS: The incidence of myoclonus was significantly lower in the
      remifentanil group (6.7%) than in the placebo group (70%) (P < 0.001). None of
      the patients experienced sedation, apnea, nausea, or pruritus after injection of
      both drugs. In the placebo group, male patients were associated with
      significantly increased incidence of myoclonus after etomidate administration.
      CONCLUSION: Pretreatment with remifentanil 1 microg/kg reduced myoclonus after
      etomidate induction without side effects such as sedation, apnea, nausea, or
      pruritus. Men experience increased incidence of myoclonus than women after
      etomidate administration.

PMID- 16563324
TI  - Different effects on circulatory control during volatile induction and
      maintenance of anesthesia and total intravenous anesthesia: autonomic nervous
      activity and arterial cardiac baroreflex function evaluated by blood pressure and
      heart rate variability analysis.
AB  - STUDY OBJECTIVE: To evaluate the different effects on autonomic circulatory
      control during volatile induction/maintenance of anesthesia (VIMA) vs total
      intravenous anesthesia (TIVA). DESIGN: Prospective study. SETTING: Operating
      theater of a university hospital. PATIENTS: Twenty patients, with American
      Society of Anesthesiologists physical status of I or II, were randomly allocated
      into the VIMA group (n = 10) or the TIVA group (n = 10). INTERVENTIONS: In the
      VIMA group, anesthesia was induced with 5% sevoflurane and 60% N2O in oxygen and
      maintained with 2% sevoflurane and 60% N2O in oxygen. In the TIVA group,
      anesthesia was induced with propofol 2.0 mg/kg intravenously by bolus injection
      and fentanyl 2 microg/kg, and maintained with an intravenous infusion of propofol
      5 mg/kg.per hour and air-oxygen mixture. MEASUREMENTS: Monitoring included
      recordings of electrocardiographic and arterial blood pressure waveforms.
      Autonomic nervous activity and arterial cardiac baroreflex function were
      evaluated by analysis of blood pressure variability, heart rate variability, and
      transfer function analysis between these 2 variables. MAIN RESULTS: In the VIMA
      group, the low-frequency component of blood pressure variability (LF(SBP)) and
      low- and high-frequency components of the R-R interval variability (LF(RR) and
      HF(RR)) decreased significantly during anesthesia. In the TIVA group, LF(SBP) and
      LF(RR) decreased significantly. The degree of reduction in LF(SBP) was greater in
      the VIMA group than in the TIVA group. However, changes in R-R interval
      variability and cardiac baroreflex indices were not significantly different
      between the 2 groups. CONCLUSIONS: Our results demonstrated that although
      reductions in autonomic nervous modulation to the heart might not be so different
      between the 2 groups, reduction in sympathetic nervous modulation to peripheral
      vasculature is greater in the VIMA group than in the TIVA group.

PMID- 16563325
TI  - Effect of synthetic colloids on major histocompatibility complex class II
      expression.
AB  - STUDY OBJECTIVE: Synthetic colloids are used for perioperative fluid management.
      We hypothesized that their use may be associated with changes in major
      histocompatibility complex (MHC) class II expression. This could affect patients'
      morbidity and mortality during clinical intervention. SETTING: University
      research laboratory. SUBJECTS: Whole blood samples from healthy volunteers.
      INTERVENTIONS: Whole blood samples from healthy volunteers (n = 6) were incubated
      with different concentrations of hydroxyethyl starch (HES) from maize and potato
      (pHES), dextran, and polygelin (gelatine) for 24 hours with or without 100 U/mL
      human interferon gamma (IFN-gamma; stimulus for MHC class II expression). The
      expression of human leukocyte antigen (HLA): HLA-DR, HLA-DQ, and HLA-DP was
      detected simultaneously by a fluoresceinisothiocyanate (FITC)-labeled antibody
      and analyzed by flow cytometry on lymphocytes and monocytes. MEASUREMENTS AND
      MAIN RESULTS: Hydroxyethyl starch, pHES, and dextran induced a significant
      increase in HLA expression. The induction of MHC class II was independent of the
      structure (50 mg/mL: control, 8.7+/-1.4%; HES, 28 +/- 9.7%; pHES, 29.8 +/- 11.7%;
      and dextran, 50.2 +/- 8.1%). In contrast, polygelin increased HLA expression only
      at the highest concentration of gelatine (5 mg/mL, 7.8 +/- 1%; 50 mg/mL, 7.6 +/-
      0.8%; 100 mg/mL, 7.3 +/- 1%; 200 mg/mL,16.2 +/- 2.3%). The addition of IFN-gamma
      decreased HLA expression in presence of highest concentration of HES and dextran.
      CONCLUSION: In an ex vivo laboratory setting, we demonstrate that high
      concentrations of plasma expanders are associated with increased HLA expression
      on lymphocytes and monocytes. However, further in vivo studies are necessary to
      demonstrate the clinical significance of this observation.

PMID- 16563326
TI  - A review of patients with pulmonary aspiration of gastric contents during
      anesthesia reported to the Departmental Quality Assurance Committee.
AB  - STUDY OBJECTIVE: Preoperative risk factors for pulmonary aspiration of gastric
      contents during anesthesia are well studied. There is lack of information as to
      factors or circumstances leading to aspiration. DESIGN: A retrospective review of
      cases of pulmonary aspiration reported to the Departmental Quality Assurance (QA)
      Committee was undertaken. SETTING: This study took place at a large tertiary care
      university hospital based in a metropolitan city. PATIENTS: The study identified
      all patients reported to the QA Committee as having pulmonary aspiration during
      January 1991 to December 1994 and July 1996 to December 2000. INTERVENTIONS: No
      interventions were done. MEASUREMENTS: The medical records of all patients thus
      identified were reviewed to see if they had pulmonary aspiration according to
      strict criteria. Presence of preoperative known risk factors, prophylactic
      measures used against pulmonary aspiration, and perioperative events were noted.
      MAIN RESULTS: A total of 47 patients were reported to the QA Committee as having
      pulmonary aspiration during this period. Upon review, 23 patients had pulmonary
      aspiration (definite aspiration, n = 12; probable aspiration, n = 11) and 24
      patients did not meet the criteria for pulmonary aspiration of gastric contents.
      The incidence of pulmonary aspiration overall was 1 per 8671 anesthetics and 1
      per 4385 anesthetics in patients younger than 16 years. If all 47 cases reported
      to QA Committee are presumed to have had pulmonary aspiration, then the overall
      incidence of aspiration is 1 in 4243 anesthetics. Eighteen of 23 patients had a
      preoperative risk factor, but preventive measures against aspiration had been
      used in only 4 patients. Five patients did not have any apparent preoperative
      risk factor. CONCLUSIONS: This study confirms that pulmonary aspiration of
      gastric contents is a rare complication during modern anesthesia. Preoperative
      risk factor was present in most patients who had pulmonary aspiration. A clear
      understanding of risk factor/s is needed to prevent further cases of pulmonary
      aspiration.

PMID- 16563327
TI  - Inhaled aerosolized iloprost in the evaluation of heart transplant candidates-
      experiences with 45 cases.
AB  - PURPOSE: Pulmonary hypertension represents a significant predictor of
      postoperative right heart insufficiency and increased mortality in patients
      undergoing orthotopic heart transplantation. As the use of intravenous
      vasodilators is limited by their systemic effects, we evaluated the pulmonary and
      systemic hemodynamic effects of inhaled aerosolized iloprost in heart transplant
      candidates with elevated pulmonary vascular resistance. METHODS: Forty-five male
      heart transplant candidates with dilated or ischemic cardiomyopathy were included
      in the study. After assessing baseline hemodynamics, 20 microg of aerosolized
      iloprost was administered by ultrasonic inhalation. All patients were breathing
      spontaneously. RESULTS: Inhalation of iloprost reduced pulmonary vascular
      resistance index (395 +/- 205 vs 327 +/- 222 dyne.s.cm(-5).m(-2); P < 0.05) and
      mean pulmonary arterial pressure (28.7 +/- 10 vs 24.3 +/- 10 mm Hg; P < 0.05). An
      additional improvement of ventricular performance with an increase of cardiac
      index (2.7 +/- 0.7 vs 3.0 +/- 0.8 L.min(-1).m(-2); P < 0.05) and a decrease of
      pulmonary capillary wedge pressure (16.6 +/- 7.7 vs 13.4 +/- 7.3 mm Hg; P < 0.05)
      was accompanied by a slight decrease of systemic vascular resistance (1280 +/-
      396 vs 1172 +/- 380 dyne.s.cm(-5); P < 0.05). However, the mean arterial pressure
      remained uninfluenced. CONCLUSIONS: Inhaled aerosolized iloprost effectively
      reduces mean pulmonary arterial pressure and also induces an increase in cardiac
      index. Further advantages of iloprost inhalation are the lack of adverse
      reactions and ease of administration. Iloprost represents a useful drug to screen
      for vascular reactivity in cardiac transplantation patients.

PMID- 16563328
TI  - A novel mixture of propofol, alfentanil, and lidocaine for regional block with
      monitored anesthesia care in ophthalmic surgery.
AB  - STUDY OBJECTIVE: The purpose of this study is to determine the efficacy and
      safety of sedation/analgesia using a mixture of propofol, alfentanil, and
      lidocaine. DESIGN: A retrospective case review was undertaken. SETTING: This
      study took place at a university medical center. PATIENTS: Eighty-nine American
      Society of Anesthesiologists physical status 1, 2, and 3 adult patients
      undergoing ophthalmic surgery with regional block and monitored anesthesia care
      were studied. INTERVENTION: Six milliliters of propofol, 2 mL of alfentanil, and
      2 mL of 2% lidocaine (6-2-2 mixture) were freshly mixed. The bolus dose was
      determined based on the patients' age: 5 microg/kg of alfentanil (and 0.3 mg/kg
      of propofol) for patients older than 75 years; the dose increased 1 mug/kg per 10
      year decrease in age; and up to 9 microg/kg of alfentanil (0.54 mg/kg of
      propofol) for patients younger than 45 years. Regional block was performed at 1
      minute after bolus completion. Blood pressure (BP), Sa(O2), electrocardiogram,
      capnography, clinical signs of sedation, responses to block, need for airway
      support, nausea and vomiting (N/V), pain due to propofol infusion, recall, and
      patient and surgeon satisfaction were recorded. MEASUREMENTS AND MAIN RESULTS:
      Seventy-eight percent of patients achieved analgesia and sedation without adverse
      response to the block. Twelve percent achieved good analgesia and sedation with
      only eyebrow movement upon needle insertion. Twenty-seven percent had respiratory
      depression but were able to follow commands and maintain adequate ventilation.
      Two percent had brief apnea alleviated by chin lift or jaw thrust. None had pain
      because of propofol infusion or N/V. Before sedation, average systolic BP was
      significantly increased (P < 0.0001) compared with baseline. After sedation and
      block, systolic BP decreased 6% from baseline (P < 0.005). CONCLUSION: Adjusted
      for age and weight, the dose of the 6-2-2 mixture met the sedation requirements
      for most patients. With a low incidence of need for airway support, no pain
      during infusion, and no N/V, this novel mixture of propofol, alfentanil, and
      lidocaine provided adequate analgesia and sedation as well as hemodynamic
      stability for ophthalmic surgery under regional block.

PMID- 16563329
TI  - Use of the Rapiscope vs chest auscultation for detection of accidental bronchial
      intubation in non-obese patients undergoing laparoscopic cholecystectomy.
AB  - STUDY OBJECTIVE: Main stem bronchial intubation is not always detected by routine
      means and may occur more frequently during laparoscopic procedures. Tracheal tube
      positional changes in non-obese patients undergoing laparoscopic cholecystectomy
      were detected by either the Rapiscope (Cook Critical Care, Bloomington, Ind) or
      chest auscultation. DESIGN: Prospective, double-blind, crossover study. SETTING:
      University hospital. PATIENTS: Forty non-obese patients (BMI <28 kg.m(-2)), aged
      18 to 80 years, American Society of Anesthesiologists risk class I-III, who
      underwent elective laparoscopic cholecystectomy were enrolled in this double
      blind, prospective study. INTERVENTIONS: After endotracheal intubation by one
      anesthesiologist, two other anesthesiologists assessed the tracheal tube's
      positioning by either the Rapiscope or chest auscultation; the results of one
      anesthesiologist's measurement were concealed from the other. MEASUREMENTS:
      Assessments of the endotracheal tube tip's position were performed after
      intubation, head-down, and head-up positioning, after maximal abdominal
      insufflation and before extubation. At the same time points, Sp(O2), ET(CO2), and
      peak inspiratory pressures were also recorded. MAIN RESULTS: Postintubation
      Rapiscope assessment revealed normal tracheal positioning of the tube's tip in
      all patients. Changes in tube's position were subsequently detected by the
      Rapiscope in 16 patients. In 8 cases, the tip moved endobronchially. Half of the
      endobronchial intubations occurred after maximal abdominal insufflation and the
      other half after changing the table position from neutral to 30 degrees head
      down. Chest auscultation detected bronchial intubation in two cases only (P =
      .01). There were 4 additional events of downward movements and 4 events of
      cephalad migration of the tube's tip identified by the Rapiscope only. ET(CO2),
      Sp(O2), and peak inspiratory pressures did not change in patients who did
      experience bronchial intubation. CONCLUSION: The Rapiscope detected significantly
      more events of endobronchial intubation as compared with chest auscultation; it
      could be considered useful during procedures where tracheal tube movements are
      potential.

PMID- 16563330
TI  - The effect of neuraxial blocks on surgical blood loss and blood transfusion
      requirements: a meta-analysis.
AB  - PURPOSE: The aim of this study was to evaluate the effect of neuraxial blocks on
      surgical blood losses and on the number of patients requiring blood transfusion.
      METHODS: A search of the American National Library of Medicine's PubMed up to
      November 12, 2004, was performed. Twenty-four studies could be kept for analysis.
      RESULTS: Regional anesthesia reduced the number of transfused patients for total
      hip replacement (P = 0.0009) and spinal fusion (P = 0.04). A reduction of
      measured blood loss that did not lead to a reduction in the number of transfused
      patients was also found for fractured hip surgery (P < 0.0001), lumbar disk
      surgery (P = 0.01), peripheral vascular surgery (P = 0.03), retropubic
      prostatectomy (P = 0.02), cesarean section (P < 0.0001), and bowel surgery (P =
      0.0008). In summary neuraxial blocks have a clear and definite effect on surgical
      blood loss, but this effect do not usually lead to a reduction in the number of
      transfused patients except for patients undergoing total hip replacement and
      spinal fusion.

PMID- 16563331
TI  - Electrocautery-induced fire during adenotonsillectomy: report of two cases.
AB  - We describe two cases of flash fires in the oropharynx, secondary to
      electrocautery during adenotonsillectomies. We believe that in both cases, the
      leak around the uncuffed endotracheal tubes raised the oxygen concentration in
      the oropharynx. Cuffed endotracheal tubes provide many advantages, and their use
      should strongly be considered during adenotonsillectomy in children when
      electrocautery is to be used.

PMID- 16563332
TI  - Inadvertent dural puncture during attempted thoracic epidural catheter placement
      complicated by cerebral and spinal subdural hematoma.
AB  - Minor complications of inadvertent dural puncture during attempted epidural
      anesthesia are common, related to the size of the needle and the incidence of
      postdural puncture headache. Serious complications are much less common. We
      report a case where inadvertent dural puncture with an 18-gauge epidural needle
      was associated with the creation of intracranial and spinal subdural hematoma.

PMID- 16563333
TI  - Subcutaneous emphysema and pneumomediastinum after translaryngeal intubation:
      tracheal perforation due to unsuccessful fiberoptic tracheal intubation.
AB  - A 77-year-old man was scheduled to undergo a cervical lymph node biopsy under
      general anesthesia. Although awake, nasotracheal fiberoptic intubation was
      initially planned because of an anticipated difficult airway, the attempt was
      unsuccessful. Orotracheal intubation was subsequently performed under direct
      laryngoscopy without difficulty. After initiating positive pressure mechanical
      ventilation, subcutaneous and mediastinal emphysema developed. The cause of this
      emphysema was considered to be tracheal perforation after an unsuccessful attempt
      at fiberoptic tracheal intubation.

PMID- 16563334
TI  - Use of ultrasonography as a rescue technique for failed radial artery
      cannulation.
AB  - Radial artery cannulation may be unsuccessful in the most experienced of hands
      using the conventional palpation method. Repeated attempts may render the
      standard wrist site difficult to cannulate due to vasospasm, hematoma formation,
      or intimal dissection. Cannulation of other arterial sites may be difficult due
      to inaccessibility or more prone to adverse outcomes. The radial artery at a
      proximal location runs deep to the brachioradialis muscle and is difficult to
      palpate; however, it can be easily imaged using real-time ultrasonography. A
      needle-mounted cannula can then be advanced in the plane of the probe and the
      pulsating artery until the needle tip is within the artery. The cannula is
      advanced over the needle so that it lies within the arterial lumen. As the
      trajectory is in full view of the ultrasound probe, the technique has a very high
      success rate. We have used ultrasonography in over 30 cases as a rescue technique
      after unsuccessful attempts at radial artery cannulation. The technique is
      described here illustrated with 3 typical cases.

PMID- 16563335
TI  - Successful epidural anesthesia for cesarean section in a parturient with severe
      aortic stenosis and a recent history of pulmonary edema--a case report.
AB  - We report a 24-year-old 36-week gestation parturient with severe aortic stenosis
      who developed pulmonary edema during amniocentesis and subsequently underwent a
      successful cesarean section under epidural anesthesia. Anesthetic management and
      some pertinent points are discussed.

PMID- 16563336
TI  - Vecuronium in a patient with late cerebellar cortical atrophy.
AB  - Little information is available regarding the sensitivity to neuromuscular
      blocking drugs in patients with spinocerebellar degeneration and associated
      diseases. We report the response to vecuronium in a patient with late cerebellar
      cortical atrophy, a nonhereditary type of cerebellar ataxia. Onset time and time
      to 25% recovery of T1/T0 after vecuronium 0.1 mg.kg(-1) under sevoflurane
      anesthesia were 156 seconds and 43 minutes, respectively. Recovery index was 27
      minutes. We believe this is the first report describing a response to
      neuromuscular blocking drugs in this disease.

PMID- 16563337
TI  - Teaching and evaluating professionalism for anesthesiology residents.
AB  - The Accreditation Council for Graduate Medical Education Outcome Project requires
      teaching and evaluation of 6 core competencies, one of which is professionalism.
      Because of this initiative, anesthesiology residency programs are obliged to
      teach and evaluate professionalism for anesthesiology residents. We decided to
      create a system that would allow the teaching and evaluation of professionalism
      in the specific context of anesthesiology.

PMID- 16563338
TI  - The use of bispectral index monitoring in the anesthetic management of a patient
      with Rett syndrome undergoing scoliosis surgery.

PMID- 16563339
TI  - Abstracts of the 1st World Congress on Gender-Specific Medicine, February 24-26,
      2006, Berlin, Germany.

PMID- 16563340
TI  - Preparation of submicron unilamellar liposomes by freeze-drying double emulsions.
AB  - A novel method is described for the preparation of sterile submicron unilamellar
      liposomes. The method is based on the lyophilization of double emulsions
      containing disaccharides as lyoprotectants in both the inner and outer aqueous
      phase. Using various phospholipids or mixtures of lipids as emulsifiers, the
      double emulsions can be prepared by a two-step emulsification, including
      hydrophilic agents in the inner aqueous phase or lipophilic agents in the oil
      phase. Then, the double emulsions are lyophilized after sterilization by passing
      them through a 0.22-microm pore filter. Rehydration of the lyophilized products
      results in liposomes with a relatively high encapsulation efficiency (for
      calcein, 87%; 5-fluorouracil, 19%; flurbiprofen, 93%) and a size below 200 nm
      measured by the dynamic light scattering technique (DLS) and the atomic force
      microscopy (AFM). The liposomes were found to be unilamellar from freeze-fracture
      electron micrographs and X-ray diffraction patterns. In addition, the liposomes
      can be reconstituted just before use by rehydration of the lyophilized products
      which are relatively stable. Thus, this reproducible and simple technique can be
      used to prepare sterilized, submicron unilamellar liposomes with a relatively
      high encapsulation efficiency, and excellent stability during long-term storage.

PMID- 16563341
TI  - The organisation and content of trauma memories in survivors of road traffic
      accidents.
AB  - We investigated the trauma narratives of 131 road traffic accident survivors
      prospectively, at 1 week, 6 weeks, and 3 months post-trauma. At 1 and 6 weeks,
      narratives of survivors with acute stress disorder (ASD) or post-traumatic stress
      disorder (PTSD) were less coherent and included more dissociation content. By 3
      months, their narratives also contained more repetition, more non-consecutive
      chunks, and more sensory words. Traumatic brain injury was associated with a
      separate characteristic, confusion, at all three time points. Three aspects of
      narrative organisation at 1 week--repetition, non-consecutive chunks, and
      coherence--predicted PTSD severity at 3 months after controlling for initial
      symptoms. The results suggest both a strong concurrent and predictive
      relationship between narrative disorganisation and ASD/PTSD but that as people
      recover from ASD, their narratives do not necessarily become less disorganised.

PMID- 16563342
TI  - Common transcriptional gene profile in neurospheres-derived from pATSCs, pBMSCs,
      and pNSCs.
AB  - Gene expression profiles of adult progenitor cells could give important clues for
      the molecular mechanisms of adult stem cell proliferation and differentiation
      behaviors. Adult bone marrow stromal cells (BMSCs), adipose tissue stromal cells
      (ATSCs), and neural stem cells (NSCs) have common neuropotential characteristics.
      They can make neurospheres and can differentiate into neurons and glia in vitro
      and in vivo. In this study, we found commonly expressed genes in neurospheres
      from non-human primate BMSCs, ATSCs, and NSCs using Affymetrix cDNA microarray
      system. The expressed genes from three distinct neurosphere populations (non
      human primate derived ATSCs neurosphere, pATSCs-NS; non-human primate derived
      BMSCs neurosphere, pBMSCs-NS; non-human primate derived NSCs neurosphere, pNSCs
      NS) were compared to baseline to calculate fold change. The number of enriched
      genes was 820 (pATSCs-NS), 856 (pBMSCs-NS), and 1010 (pNSCs-NS). Scatter plots of
      expression levels of all the genes indicated that the correlation coefficients
      between the three samples are fairly close to each other and have many
      similarities at the transcriptional levels. Finally, we found that the expression
      of 184 genes is enriched in all three categories, 9 selected to regulation of
      cell cycle, 5 transcription factor, 9 receptor activity, 11 development, and 4
      cell-cell signaling. This overlapping gene set of commonly expressed gene
      products represents a molecular signature of neural lineage related function.

PMID- 16563343
TI  - Identification and characterization of collagen-binding activity in Streptococcus
      mutans wall-associated protein: a possible implication in dental root caries and
      endocarditis.
AB  - Streptococcus mutans is implicated in coronal and dental root decay, and in
      endocarditis. Comparative study of the amino acid sequence of S. mutans 47 kDa
      wall-associated protein A (WapA) revealed a collagen-binding domain (CBD) at the
      N-terminal region. Recombinant AgA (WapA truncated at the carboxyterminal end)
      was isolated, biotin-labeled, and analyzed by Solid Phase Binding Assay. The
      results showed that biotin-labeled AgA bound significantly and in a dose
      dependent manner to immobilized collagen type I, and to a lesser extent to
      fibronectin, but not to collagen type IV or laminin. Binding of biotin-labeled S.
      mutans cells to collagen-coated surfaces was significantly inhibited by antibody
      to WapA or AgA (P<0.001). The results obtained confirmed the collagen-binding
      activity of CBD in AgA and WapA, and suggested that WapA may be used, not only as
      a vaccine against coronal and dental root caries, but also against S. mutans
      mediated endocarditis.

PMID- 16563344
TI  - Fluorescence-coupled CD conformational monitoring of filament formation of tau
      microtubule-binding repeat domain.
AB  - To clarify the contribution of the three- or four-repeated peptide moiety in tau
      microtubule-binding domain (MBD) to paired helical filament (PHF) formation,
      conformational transition accompanied by heparin-induced filament formation was
      investigated stepwise for four repeat peptides (R1-R4), one three-repeated R1-R3
      R4 peptide (3RMBD), and one four-repeated R1-R2-R3-R4 peptide (4RMBD) using a
      combination of thioflavin S fluorescence and circular dichroism (CD) measurements
      in a neutral buffer (pH 7.6). The comparison of the fluorescence profile of each
      repeat peptide with those of 3RMBD and 4RMBD showed the synergistic contribution
      of R1-R4 to PHF formation of MBD. The CD spectrum measured as a function of
      filament formation time indicates that: (i) two conformational transitions occur
      for the filament formations of R3 (from the random structure to the beta-sheet
      structure) and 3RMBD (from the random structure to the alpha-helix structure),
      (ii) the filament formations of R2 and 4RMBD proceed via the synchronized
      conformational transitions of the alpha-helix and random structures, and (iii)
      the filament formation of 4RMBD is dependent on the aggregation behavior of R2.
      These data are useful for elucidating the MBD conformational transition in tau
      PHF formation.

PMID- 16563345
TI  - The role of endoribonucleases in the regulation of RNase R.
AB  - RNase R is an important exoribonuclease involved in the maturation and
      degradation of RNA. RNase R is co-transcribed with other genes in the same
      operon. In this report, we show that under physiological conditions maturation of
      these co-transcripts and the levels of RNase R are mainly dependent on the
      endoribonuclease RNase E. The presence of the full-length RNase E is necessary
      for the decay of intermediary products that arise from the maturation of
      transcripts from the rnr operon. RNase G and RNase III do not seem to have a
      primary role in the processing of the rnr transcripts. However, the accumulation
      of intermediary transcripts in an rng mutant suggests that RNase G may act in the
      degradation of the transcripts already cleaved by RNase E. These results
      demonstrated that other ribonucleases can act as an additional level of
      regulation in the control of the expression of RNase R.

PMID- 16563346
TI  - Molecular cloning of pigGnT-I and I.2: an application to xenotransplantation.
AB  - Xenotransplantation is one of the most attractive solutions for the current
      worldwide shortage of organs. The knocking out of alpha1,3-galactosyltransferase
      in pigs resulted in a drastic reduction in xenoantigenicity. However, more recent
      studies indicate that other xeno-antigens, so-called non-Gal antigens, will also
      need to be downregulated. In this study, pig N-acetylglucosaminyltransferase I
      (GnT-I), a key enzyme that initiates the biosynthesis of hybrid- and complex-type
      N-linked sugar chains, was isolated and the pigGnT-I.2 specific for the O-linked
      sugar chain was also isolated. Point mutants, pigGnT-I(123) and pigGnT-I(320),
      were subsequently constructed. While pigGnT-I(123) shows an indistinct dominant
      negative effect for endogenous GnT-I in pig cells, pigGnT-I(320) had a drastic
      effect. In addition, in the case of pig cell transfectants with pigGnT-I(320),
      cell surface carbohydrate structures were significantly altered and its
      antigenicity to human serum was reduced. Consequently, pigGnT-I(320) appears to
      be potentially useful in xenotransplantation by remodeling the carbohydrate
      structures on pig cells.

PMID- 16563347
TI  - Tissue-specific effects of statins on the expression of heme oxygenase-1 in vivo.
AB  - Heme oxygenase-1 (HO-1) plays a central role in antioxidant and anti-inflammatory
      actions, which may be mediated through its formation of biliverdin/bilirubin and
      carbon monoxide. HMG-CoA reductase inhibitors (statins) induce in vitro HO-1
      expression and are reported to have pleiotropic benefits that reduce oxidative
      stress in the vasculature. We characterized the effects of statins on in vivo HO
      1 expression in various extravascular tissues: liver, lung, brain, and heart.
      Adult mice were orally administered simvastatin, lovastatin, atorvastatin, or
      rosuvastatin. HO activity significantly increased in a statin- and tissue
      specific manner, with all statins increasing heart and lung activity within 24 h.
      Significant elevations of HO-1 protein and mRNA were also observed in heart and
      lung after atorvastatin treatment. We conclude that in vivo HO-1 induction is
      statin- and tissue-specific. Through this pathway, statins may confer antioxidant
      and anti-inflammatory actions in the vasculature and extravascular systems.

PMID- 16563348
TI  - Activation of the human pregnancy-specific glycoprotein PSG-5 promoter by KLF4
      and Sp1.
AB  - Pregnancy-specific glycoproteins (PSGs) are major placental proteins thought to
      be essential for the maintenance of gestation. Little is known about the
      regulation of expression of the 11 genes encoding these proteins. It was
      previously demonstrated that Kruppel-like factor 6 (KLF6) and specific-protein 1
      (Sp1) bind to conserved sequence within the PSG-5 gene promoter. Informatics
      analysis revealed the presence of one potential binding site for Kruppel-like
      factor 4 (KLF4), in the PSG-5 promoter, suggesting a potential transcriptional
      regulator role for KLF4. Using gene promoter-reporter transfections and X-ChIP
      assays, we demonstrated that KLF4 is an activator of the PSG-5 promoter by
      binding to a KLF consensus like binding which includes the Core Promoter Element
      region (-147/-140). Furthermore, we used previous data showing the binding of Sp1
      transcription factor to a GT-box (-443/-437) and co-transfection assays with KLF4
      and Sp1 to demonstrate the strong synergic activity of these two factors on the
      PSG-5 promoter.

PMID- 16563349
TI  - Intra-tumoural regulatory T cells: a potential new target in cancer
      immunotherapy.
AB  - We hypothesised that T(reg) cells preferentially expand/infiltrate inside murine
      mesotheliomas. Immunotherapy based on the manipulation of T(reg) cell populations
      should therefore be targeted to the tumour site. The AE17 murine mesothelioma
      model was used for this study. Both intra-tumoural T(reg) cells and those in the
      periphery of tumour-bearing mice were identified by flow cytometry. The effect on
      tumour growth of intra-tumoural depletion of T(reg) cells using the PC61 anti
      CD25 mAb was then examined. We identified CD4+ T(reg) cells co-expressing both
      the CD25 cell surface marker and the transcription factor Foxp3 within murine
      mesotheliomas. These intra-tumoural T(reg) cells increase significantly as a
      percentage of total CD4+ T cells within the tumour as it grows. We showed that
      the depletion of intra-tumoural T(reg) cells with anti-CD25 mAb injected directly
      into the tumours can cause significantly reduced tumour growth. Localised, intra
      tumoural depletion of T(reg) cells is a new, clinically relevant treatment option
      for established tumours.

PMID- 16563350
TI  - Cytokine secretion by human adipocytes is differentially regulated by
      adiponectin, AICAR, and troglitazone.
AB  - Adipose tissue is an active endocrine organ producing a variety of cytokines and
      chemokines, which may be involved in the deregulation of glucose and lipid
      homeostasis as well as in the inflammatory state observed in obesity. We have
      shown previously that differentiated human adipocytes secrete a variety of
      cytokines which are able to induce skeletal muscle insulin resistance. However,
      the regulation of these factors by anti-diabetic drugs has remained mainly
      undefined. Secretion of IL-6, IL-8, MIP-1alpha/beta, and MCP-1 by adipocytes was
      found to be downregulated by adiponectin. In parallel to adiponectin, the AMPK
      activator AICAR also decreased the secretion of most of the measured cytokines
      including IL-6 and MIP-1alpha/beta but not IL-8. In contrast, the
      thiazolidinedione troglitazone only slightly reduced cytokine secretion despite
      increasing the phosphorylation of AMPK. In conclusion, we show that adipocyte
      secretion is strongly inhibited by the anti-diabetic adipocyte hormone
      adiponectin, an effect that can also be mimicked by the AMPK activator AICAR.
      However, the PPARgamma agonist troglitazone is much less effective in reducing
      cytokine secretion.

PMID- 16563351
TI  - Two closely related nickel complexes have different effects on DNA damage and
      cell viability.
AB  - Nickel is considered a weak carcinogen. It is known to interact with DNA and DNA
      binding proteins. The ability of certain nickel compounds to cleave DNA has been
      exploited mainly for research purposes and less for developing new anticancer
      drugs. Here we compare the interactions of two closely related nickel complexes,
      [NiCR]2+ and [Ni(CR-2H)]2+, with DNA. CR stands for 2,12-dimethyl-3,7,11,17
      tetraazabicyclo-[11.3.1]-heptadeca-1(17),2,11,13,15-pentaene. [NiCR]2+ has been
      used in the past as a structure-specific probe for RNA and DNA oligonucleotides
      in the presence of oxidizing agent but little is known about the biological
      effects of either complex. Our results show that [Ni(CR-2H)]2+ can damage DNA in
      vivo and in vitro in the absence of an added oxidizing agent and has an IC50 of
      70 microM in human breast cancer cells whereas [NiCR]2+ and NiCl2 do not exhibit
      significant cytotoxicity. However, both [NiCR]2+ and [Ni(CR-2H)]2+ bind to the
      minor groove of double-stranded DNA.

PMID- 16563352
TI  - Binding of bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine
      to wild-type and F120A mutant cytochrome P450 2D6 studied by resonance Raman
      spectroscopy.
AB  - Cytochrome P450 2D6 (CYP2D6) is one of the most important drug-metabolizing
      enzymes in humans. Resonance Raman data, reported for the first time for CYP2D6,
      show that the CYP2D6 heme is found to be in a six-coordinated low-spin state in
      the absence of substrates, and it is perturbed to different extents by bufuralol,
      dextromethorphan, and 3,4-methylenedioxymethylamphetamine (MDMA).
      Dextromethorphan and MDMA induce in CYP2D6 a significant amount of five
      coordinated high-spin heme species and reduce the polarity of its heme-pocket,
      whereas bufuralol does not. Spectra of the F120A mutant CYP2D6 suggest that
      Phe120 is involved in substrate-binding of dextromethorphan and MDMA, being
      responsible for the spectral differences observed between these two compounds and
      bufuralol. These differences could be explained postulating a different substrate
      mobility for each compound in the CYP2D6 active site, consistently with the role
      previously suggested for Phe120 in binding dextromethorphan and MDMA.

PMID- 16563353
TI  - The Escherichia coli thioredoxin homolog YbbN/Trxsc is a chaperone and a weak
      protein oxidoreductase.
AB  - Escherichia coli contains two thioredoxins, Trx1 and Trx2, and a thioredoxin-like
      protein, YbbN, which presents a strong homology in its N-terminal part with
      thioredoxin 1 and 2. YbbN, however, does not possess the canonical Cys-x-x-Cys
      active site of thioredoxins, but instead a Ser-x-x-Cys site. In addition to Cys
      38, located in the SxxC site, it contains a second cysteine, Cys-63, close to Cys
      38 in the 3D model. Cys-38 and Cys-63 undergo an oxidoreduction process,
      suggesting that YbbN functions with two redox cysteines. Accordingly, YbbN
      catalyzes the oxidation of reduced RNase and the isomerization of scrambled
      RNase. Moreover, upon oxidation, its oligomeric state changes from dimers to
      tetramers and higher oligomers. YbbN also possesses chaperone properties,
      promoting protein folding after urea denaturation and forming complexes with
      unfolded proteins. This is the first biochemical characterization of a member of
      the YbbN class of bacterial thioredoxin-like proteins, and in vivo experiments
      will allow to determine the importance of its redox and chaperone properties in
      the cellular physiology.

PMID- 16563354
TI  - False positives in MALDI-TOF detection of ERbeta in mitochondria.
AB  - Recently, Yang et al. reported that estrogen receptor beta (ERbeta) is a
      mitochondrial protein rather than a nuclear receptor. Because this claim would
      lead to a significant change in our understanding of estrogen signaling, we have
      attempted to reproduce the MALDI-TOF data of Yang et al. We separated proteins
      extracted from mouse liver mitochondria by SDS-PAGE and analysed a gel band
      covering the molecular weight range of 50-65 kDa by MALDI-TOF/TOF. Analysis of
      the data with the MASCOT database algorithm provided no evidence for the presence
      of ERbeta in the mitochondria. If we search (as the authors did) with only the
      peptide masses which match to tryptic fragments of ERbeta, ERbeta is identified
      with a significant score of 69. However, fragmentation of these peptides shows
      that they are not from ERbeta. Our conclusion is that ERbeta cannot be identified
      by MALDI-TOF from a mixture of mitochondrial proteins resolved on SDS-PAGE.

PMID- 16563355
TI  - High-affinity binding of the NC1 domain of collagen VII to laminin 5 and collagen
      IV.
AB  - Anchoring functions of collagen VII depend on its ability to form homotypic
      fibrils and to bind to other macromolecules to form heterotypic complexes.
      Biosensor-based binding assays were employed to analyze the kinetics of the NC1
      domain-mediated binding of collagen VII to laminin 5, collagen IV, and collagen
      I. We showed that collagen VII interacts with laminin 5 and collagen IV with a Kd
      value of 10(-9) M. In contrast, the NC1-mediated binding to collagen I was weak
      with a Kd value of 10(-6) M. Binding assays also showed that the NC1 domain
      utilizes the same region to bind to both laminin 5 and collagen IV. We postulate
      that the ability of the NC1 domains to bind with high affinities to laminin 5 and
      collagen IV facilitates stabilization of the structure of the basement membrane
      itself and that the NC1-collagen I interaction may be less important for
      stabilization of the dermal-epidermal junction.

PMID- 16563356
TI  - Alteration of familial ALS-linked mutant SOD1 solubility with disease
      progression: its modulation by the proteasome and Hsp70.
AB  - Accumulation of misfolded Cu/Zn superoxide dismutase (SOD1) occurs in patients
      with a subgroup of familial amyotrophic lateral sclerosis (fALS). To identify the
      conversion of SOD1 from a normally soluble form to insoluble aggregates, we
      investigated the change of SOD1 solubility with aging in fALS-linked H46R SOD1
      transgenic mice. Mutant SOD1 specifically altered to insoluble forms, which were
      sequentially separated into Triton X-100-insoluble/sodium dodecyl sulfate (SDS)
      soluble and SDS-insoluble/formic acid-soluble species. In spinal cords, the
      levels of SDS-dissociable soluble SOD1 monomers and SDS-stable soluble dimers
      were significantly elevated before motor dysfunction onset. In COS-7 cells
      expressing H46R SOD1, treatment with proteasome inhibitors recapitulated the
      alteration of SOD1 solubility in transgenic mice. In contrast, overexpression of
      Hsp70 reduced accumulation of mutant-specific insoluble SOD1. SDS-soluble low
      molecular weight species of H46R SOD1 may appear as early misfolded intermediates
      when their concentration exceeds the capacity of the proteasome and molecular
      chaperones.

PMID- 16563357
TI  - Molecular targets of dietary agents for prevention and therapy of cancer.
AB  - While fruits and vegetables are recommended for prevention of cancer and other
      diseases, their active ingredients (at the molecular level) and their mechanisms
      of action less well understood. Extensive research during the last half century
      has identified various molecular targets that can potentially be used not only
      for the prevention of cancer but also for treatment. However, lack of success
      with targeted monotherapy resulting from bypass mechanisms has forced researchers
      to employ either combination therapy or agents that interfere with multiple cell
      signaling pathways. In this review, we present evidence that numerous agents
      identified from fruits and vegetables can interfere with several cell-signaling
      pathways. The agents include curcumin (turmeric), resveratrol (red grapes,
      peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl
      cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli),
      diosgenin (fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic
      acid (apple, pears, prunes), silymarin (milk thistle), anethol (anise, camphor,
      and fennel), catechins (green tea), eugenol (cloves), indole-3-carbinol
      (cruciferous vegetables), limonene (citrus fruits), beta carotene (carrots), and
      dietary fiber. For instance, the cell-signaling pathways inhibited by curcumin
      alone include NF-kappaB, AP-1, STAT3, Akt, Bcl-2, Bcl-X(L), caspases, PARP, IKK,
      EGFR, HER2, JNK, MAPK, COX2, and 5-LOX. The active principle identified in fruit
      and vegetables and the molecular targets modulated may be the basis for how these
      dietary agents not only prevent but also treat cancer and other diseases. This
      work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine
      and medicine be thy food.

PMID- 16563359
TI  - The promise of stem cells for neural repair.
AB  - The realization that the adult nervous system develops from multipotential stem
      cells and that cells with stem-like properties are retained in the adult CNS has
      provoked an intense search for ways to utilize their potential for therapeutic
      treatments of multiple neurological disorders. Transplantation of neural stem
      cells or more restricted progenitors to replace cells lost to injury or disease
      may facilitate functional recovery in a spectrum of neurological disorders.
      Alternatively, expansion and recruitment of endogenous progenitors may be
      effective in treating widespread cell loss in the adult CNS. A major challenge to
      the development of effective stem cell therapies is to direct the fate of the
      newly generated cells to specifically replace those lost to disease. Insights
      from developmental research are providing molecular targets for regulating the
      differentiation of neural stem cells and their progeny in areas of injury to the
      adult CNS. Given the commonality of processes mediating the assembly of
      multicellular systems, the approaches developed in the CNS will likely be
      applicable for selective cell replacement in the auditory system.

PMID- 16563358
TI  - Amphetamine withdrawal leads to behavioral sensitization and reduced HPA axis
      response following amphetamine challenge.
AB  - Withdrawal from repeated amphetamine (AMPH) administration leads to behavioral
      sensitization following a drug or a stress challenge and is commonly used to
      model anhedonia in rats, a core symptom of depression in humans. It is proposed
      that corticosteroids are involved in the mediation of sensitization and
      depression. The aim of the present study was to investigate stress and AMPH-
      induced release of adrenocorticotropic hormone (ACTH) and corticosterone (CORT)
      during withdrawal from an escalating dosage schedule of AMPH known to produce
      depression-like effects in rats. Wistar rats were given 3 injections (i.p.) per
      day over 3 days, escalating from 1 mg/kg to 9 mg/kg and a final injection of 10
      mg/kg AMPH or saline on day 4. On day 2 of withdrawal, the animals were tested in
      the Porsolt swim test. HPA axis activity in response to restraint stress was
      tested on withdrawal day 14 and in response to AMPH challenge on withdrawal day
      30. We found no effect of AMPH withdrawal in the Porsolt swim test and on the
      ACTH or CORT response following restraint stress. AMPH withdrawn animals
      expressed behavioral sensitization in terms of locomotion and reduced ACTH and
      CORT plasma levels following a 1 mg/kg AMPH challenge in comparison to the
      controls. We conclude that there is no critical involvement of a sensitized HPA
      axis stress response in the long-term expression of behavioral sensitization.

PMID- 16563360
TI  - Involvement of nociceptin/orphanin FQ and its receptor in electroacupuncture
      produced anti-hyperalgesia in rats with peripheral inflammation.
AB  - The neuropeptide nociceptin/orphanin FQ (N/OFQ), the endogenous agonist of the
      N/OFQ peptide receptor (NOP receptor), has been demonstrated to be involved in
      many physiological and pathological functions including pain regulation. In the
      present study, the involvement of N/OFQ-NOP receptor system in electroacupuncture
      (EA)-produced anti-hyperalgesia was investigated in rats with peripheral
      inflammation. Intrathecal (i.t.) administration of N/OFQ (15 nmol) or EA at
      acupoints GB30 and GB34 could significantly attenuate hyperalgesia which was
      induced by subcutaneously injecting complete Freund's adjuvant (CFA) into one
      hindpaw of rats, manifesting as decreased paw withdrawal latency (PWL) to the
      noxious thermal stimulus. The anti-nociceptive effect of N/OFQ or EA was
      significantly blocked by intrathecal injection of [Nphe(1)]nociceptin(1-13)NH(2)
      (20 nmol), a selective antagonist of the NOP receptor, indicating the NOP
      receptor-mediated mechanism. Additionally, the combination of N/OFQ injection
      with EA treatment could enhance anti-hyperalgesia compared to that produced by
      each component alone. These findings suggested that the spinal N/OFQ-NOP system
      might be involved in EA analgesia, which may be one of the mechanisms underlying
      the anti-nociceptive effect of EA in rat's peripheral inflammatory pain.

PMID- 16563361
TI  - The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial
      infarction model.
AB  - OBJECTIVE: This study was designed to examine whether mesenchymal stem cells
      (MSCs) transduced with Akt enhance cardiac repair after transplantation into the
      ischemic porcine heart. METHODS: MSCs isolated from porcine bone marrow and
      transduced with myr-Akt were transplanted into porcine hearts after experimental
      myocardial infarction (MI) using intracoronary injection [Group I, vehicle; Group
      II, MSCs; Group III, Akt-MSCs]. Myocardial single photon emission tomography (M
      SPECT) was performed to assess myocardial function and the infarcted area. Pigs
      were also sacrificed for immunohistochemical characterization and histologic
      analysis. In addition, in vitro assays were performed to examine the resistance
      of Akt-MSCs to H(2)O(2) stimulation. RESULTS: Transplantation of MSCs into the
      ischemic porcine myocardium (Group II) increased the left ventricular ejection
      fraction (DeltaLV EF; -6.3 +/- 15.1% versus 0.5 +/- 6.4%, P < 0.001) and
      decreased the Deltaarea of MI (6.8+/-5.6% versus -5.0+/-5.3%, P < 0.001) compared
      with the vehicle control (Group I). Transplantation of MSCs transduced with myr
      Akt (Group III) resulted in further improvement in DeltaLV EF (-6.3 +/- 15.1%
      versus 5.8 +/- 11.3%, P < 0.001) and in Deltaarea of MI (6.8 +/- 5.6% versus 
      17.0 +/- 7.6%, P < 0.001). Akt-MSCs were more resistant to apoptosis, and the
      levels of extracellular signal-regulated protein kinase (ERK) activation and
      vascular endothelial growth factor (VEGF) were higher in H(2)O(2)-stimulated Akt
      MSCs. CONCLUSION: Cellular transplantation of Akt-MSCs further enhances the
      repair of injured myocardium compared to MSC transplantation alone by increasing
      the number of viable MSCs after cellular transplantation.

PMID- 16563362
TI  - Vitamin D receptor polymorphisms and diseases.
AB  - The vitamin D endocrine system is central to the control of bone and calcium
      homeostasis. Thus, alterations in the vitamin D pathway lead to disturbances in
      mineral metabolism. Furthermore, a role for vitamin D has been suggested in other
      diseases, like cancer, diabetes and cardiovascular disease. Expression and
      nuclear activation of the vitamin D receptor (VDR) are necessary for the effects
      of vitamin D. Several genetic variations have been identified in the VDR. DNA
      sequence variations, which occur frequently in the population, are referred to as
      "polymorphisms" and can have biological effects. To test whether there is a
      linkage between VDR polymorphisms and diseases, epidemiological studies are
      performed. In these studies, the presence of a variation of the gene is studied
      in a population of patients, and then compared to a control group. Thus,
      association studies are performed, and a link among gene polymorphisms and
      diseases can be established. Since the discovery of VDR polymorphisms a number of
      papers have been published studying its role in bone biology, renal diseases,
      diabetes, etc. The purpose of this review is to summarize the vast amount of
      information regarding vitamin D receptor polymorphisms and human diseases, and
      discuss its possible role as diagnostic tools.

PMID- 16563363
TI  - A novel Val734Ile variant in the ABCC9 gene associated with myocardial
      infarction.
AB  - BACKGROUND: Alterations in coronary vasomotor tone are deemed to play an
      important role in myocardial infarction (MI), and the ATP-binding cassette
      transporter C9-ABCC9-may be involved in the regulation of coronary artery
      vasomotility. We sought to determine whether genetic variations in the coding
      sequence of ABCC9 gene could be associated with precocious MI (myocardial
      infarction before the age of 60 years) in humans. METHODS: In this study, we
      screened using PCR-SSCP analysis the entire coding region of the ABCC9 gene in 45
      patients with precocious MI and 45 age- and gender-matched controls. RESULTS: A
      novel missense mutation, Val734Ile in exon 17, was detected in one MI patient. We
      therefore analyzed by PCR-RFLPs the frequency of this nonsynonymous change in a
      large Italian cohort of precocious MI patients (n=584) and healthy comparison
      subjects (n=873). After allowance for the potential confounding effects of age,
      gender, and established cardiovascular risk factors, multivariate logistic
      regression analysis revealed that carriers of the rare 734Ile allele would have a
      6.40-fold risk of suffering MI before the age of 60 years as compared to controls
      (95% CI=1.58-25.90, P=0.009). CONCLUSIONS: Taken together, our results provide
      the first important evidence that the newly discovered 734Ile allele in ABCC9
      might influence susceptibility to precocious MI in our population.

PMID- 16563364
TI  - Comparison of fatty acid profiles of aorta and internal mammary arteries in
      patients with coronary artery disease.
AB  - BACKGROUND: Atherosclerosis represents the principal cause of death in the many
      societies. Since few data have been published about the composition of fatty
      acids in atherosclerotic arteries such as the aorta comparing to the non affected
      internal mammary artery which is used for aortocoronary bypass grafting, we
      compared the fatty acid profiles of atherosclerotic aorta and internal mammary
      arteries in human individuals. METHODS: Twenty-one angiographically documented
      coronary artery disease (CAD) patients who were admitted to the open heart
      surgery division enrolled in this study. They were operated electively for
      coronary artery bypass grafting surgery (CABG). Small segments of ascending aorta
      and internal mammary arteries were sampled during open heart surgery. The samples
      were subjected to lipid extraction and fatty acid analysis by high performance
      liquid chromatography. RESULTS: The results showed that different fatty acid
      profiles were seen in the aorta and internal mammary arteries. The
      atherosclerotic aorta contained lower amounts of unsaturated fatty acids
      (including trans isomer of oleic acid) and higher proportions of saturated fats
      comparing to the internal mammary. In the aorta also, the amounts of omega6
      series of fatty acids were more and levels of omega3 fats were less than the
      internal mammary. CONCLUSION: This study suggests that modification of fatty
      acids may play a role during atherogenesis.

PMID- 16563365
TI  - Expanded newborn screening of inherited metabolic disorders by tandem mass
      spectrometry: clinical and laboratory aspects.
AB  - Newborn screening started in the 1960s for the purpose of identifying
      phenylketonuric patients to begin early intervention and to prevent mental
      retardation in these patients. Soon thereafter, screening programs expanded to
      include additional genetic disorders added individually one at a time. In the
      1980s, tandem mass spectrometry (MS/MS) was introduced in clinical laboratories,
      and in the 1990s, the technique was used for newborn screening. Unlike measuring
      one analyte at a time, MS/MS allows measurement of >40 analytes, in a few minutes
      with the use of a single assay. Currently, MS/MS is being used for the
      identification of several amino acid, organic acid and fatty acid disorders.
      Several states in the United States and many other countries are using MS/MS in
      newborn screening. However, there is a significant disparity among different
      newborn screening programs for disorders being screened by MS/MS and many other
      challenges are faced by the expanded newborn screening. It is anticipated that in
      the future the use of MS/MS in newborn screening will expand both at the analyte
      and geographic levels. Clinicians and laboratory scientists should become
      familiar with MS/MS, disorders being screened in their patients' population and
      the future of this emerging technology.

PMID- 16563367
TI  - Effects of auditory pattern structure on anticipatory and reactive attending.
AB  - In three experiments, participants listened for a target's pitch change within
      recurrent nine-tone patterns having largely isochronous rhythms. Patterns
      differed in pitch structure of initial (context) and final (target distance)
      pattern segments. Also varied were: probe timing (Experiments 2 and 3) and
      instructions about probe timing (Experiments 2 and 3). In all experiments,
      identification of a recurrent target was poorer in patterns with wider context
      pitch intervals (in semitones) than in others. Effects of probe timing also
      occurred, with better performance for temporally expected than unexpected probes.
      However, when listeners were explicitly told to focus upon a target's pitch and
      not its timing (Experiment 3), they performed selectively better in patterns with
      smaller target/probe pitch distances, especially for rhythmically expected
      probes. Five theoretical approaches to the respective roles of pitch and/or time
      structure were assessed. Although no single approach accounted for all results, a
      modification of one theory (a Pitch/Time Entrainment model) provided a reasonable
      description of findings.

PMID- 16563366
TI  - Comparative study between the Light Cycler and the PCR-restriction fragment
      length polymorphism in detecting factor V Leiden and factor II 20210G>A
      mutations.
AB  - OBJECTIVES: To test reproducibility, speed and cost of testing for factor V
      Leiden and FII 20210G>A in our practice. DESIGN AND METHODS: We compared
      conformity, reproducibility, speed and cost using the Light Cycler (LC) and PCR
      RFLP. RESULTS: There was 100% conformity and reproducibility. LC was faster but
      23% more expensive per sample. When equipment depreciation and patient expenses
      are added, LC testing becomes cheaper. CONCLUSION: In our practice, LC provides
      fast, reproducible and cost-effective results.

PMID- 16563368
TI  - Wnt signal transduction and the formation of the myocardium.
AB  - Soon after fertilization, vertebrate embryos grow very rapidly. Thus, early in
      gestation, a sizeable yet underdeveloped organism requires circulating blood.
      This need dictates the early appearance of a contractile heart, which is the
      first functional organ in both the avian and mammalian embryo. The heart arises
      from paired mesodermal regions within the anterior half of the embryo. As
      development proceeds, these bilateral precardiac fields merge at the midline to
      give rise to the primary heart tube. How specific areas of nondifferentiated
      mesoderm organize into myocardial tissue has been a question that has long
      intrigued developmental biologists. In recent years, the regulation of Wnt signal
      transduction has been implicated as an important event that initiates cardiac
      development. While initial reports in Drosophila and the bird had implicated Wnt
      proteins as promoters of cardiac tissue formation, subsequent findings that the
      WNT inhibitors Dkk1 and crescent possess cardiac-inducing activities led to the
      contrary hypothesis that WNTs actively inhibit cardiogenesis. This seeming
      contradiction has been resolved, in part, by more recent information indicating
      that Wnts stimulate multiple signal transduction pathways. In this review, we
      will examine what is presently known about the importance of regulated Wnt
      activity for the formation of the heart and the development of the myocardium and
      discuss this information in context of the emerging complexity of Wnt signal
      transduction.

PMID- 16563369
TI  - Associations of organochlorines with endogenous hormones in male Great Lakes fish
      consumers and nonconsumers.
AB  - This study investigated the relationships of steroid and thyroid hormones with
      total noncoplanar polychlorinated biphenyls (PCBs), total toxic equivalents
      (TEQs) from dioxins-like organochlorines, and dichlorodiphenyl dichloroethene
      (DDE) in 56 male frequent and infrequent Great Lakes sport caught fish consumers.
      Significant negative associations were found for triiodothyronine (T3), thyroxine
      (T4), thyroid stimulating hormone (TSH), and sex hormone binding globulin (SHBG)
      bound testosterone with PCBs, for TSH with total TEQs, and for estrone sulfate
      with DDE, adjusting for age, body mass index, and medication use. Follicle
      stimulating hormone, luteinizing hormone, free testosterone, and SHBG were not
      significantly associated with organochlorines. Models that accounted for exposure
      to both PCBs and TEQs predicted T4, estrone sulfate, and SHBG-bound testosterone
      better than models that included either PCBs or TEQs alone, with the lowest
      hormone levels occurring in the participants with both higher PCB levels and
      lower TEQ levels. These data suggest that exposure to PCBs, dioxin-like
      organochlorines, and DDE, alone and potentially in combination, may be associated
      with effects on the endocrine system in adult males. Further studies should help
      delineate specific exposure effects and effects of exposures to other common
      environmental contaminants alone and in combination with PCBs.

PMID- 16563370
TI  - The impact of aerial application of organophosphates on the cholinesterase levels
      of rural residents in the Vaalharts district, Northern Cape Province, South
      Africa.
AB  - A cluster of Guillaine-Barre syndrome cases in the Vaalharts region, South Africa
      prompted an investigation of the impact of aerial organophosphate spraying on
      cholinesterase levels of residents in the region. A prospective study of
      cholinesterase levels among residents and workers in the area and a control area
      was performed. Standardized red blood cell cholinesterase levels amongst
      participants were monitored before (round 1), during (round 2), and after (round
      3) the 1996/1997 aerial spraying season. Participants were assigned environmental
      exposure categories based on the time since (within 10 or 30 days) and distance
      from (on farm, on neighboring farm, <10 km from farm) aerial pesticide
      application. There were 342 participants in round 1, of whom 78% participated in
      round 2, 62% in round 3, and 56% in all three rounds. There was an increase in
      cholinesterase levels in round 2 (mean increase = 5.96+/-6.25 IU/g hemoglobin)
      and then a decrease in round 3 (6.17+/-6.51), significantly associated with
      environmental exposure (participants living on farm or neighboring farm and <10
      km from spraying area) controlling for age, gender, alcohol dependence, and usual
      and recent domestic and occupational pesticide use (e.g., for round 2-round 1
      cholinesterase differences, beta; (exposed group relative to unexposed)=5.72+/
      1.21 IU/g hemoglobin, P = 0.000, R2 = 0.27, n = 171). The results show a shift in
      cholinesterase levels associated with residence in the spraying area, but in the
      direction opposite to that expected from the spraying of pesticides. Seasonal
      fluctuations in ambient temperature during the study may have influenced the
      results.

PMID- 16563371
TI  - Effects of particulate air pollution on systolic blood pressure: A population
      based approach.
AB  - Given the hypothesis that particulate air pollution is associated with systolic
      blood pressure, the effect of daily concentrations of air pollution on blood
      pressure was assessed in 2612 elderly subjects in the urban area of Bordeaux,
      France. Blood pressure was measured by a digital monitor. Particle concentrations
      (PM10) were obtained from the AIRAQ association that operates a local monitoring
      network of the air quality. To represent the ambient urban air pollution,
      stations had to be sufficiently correlated (i.e., correlation >0.70) and to have
      sufficiently similar mean levels of pollution. Linear regression was used to
      model the association between concentrations of particles (PM10) and systolic
      blood pressure. We observed associations between the fifth lag hour and systolic
      blood pressure for an increase of 10 microg/m3 of PM10 (beta = -1.12, 95%
      confidence interval: [-1.90; -0.30]). Despite contradictory results, fine
      particles must be considered nowadays as a major component of atmospheric air
      pollution in which everything must be put into practice in terms of public health
      actions in order to protect the general population and particularly the elderly
      group.

PMID- 16563372
TI  - C3-halogenation of cytisine generates potent and efficacious nicotinic receptor
      agonists.
AB  - Neuronal nicotinic acetylcholine receptors subserve predominantly modulatory
      roles in the brain, making them attractive therapeutic targets. Natural products
      provide key leads in the quest for nicotinic receptor subtype-selective
      compounds. Cytisine, found in Leguminosae spp., binds with high affinity to
      alpha4beta2* nicotinic receptors. We have compared the effect of C3 and C5
      halogenation of cytisine and methylcytisine (MCy) on their interaction with
      native rat nicotinic receptors. 3-Bromocytisine (3-BrCy) and 3-iodocytisine (3
      ICy) exhibited increased binding affinity (especially at alpha7 nicotinic
      receptors; Ki approximately 0.1 microM) and functional potency, whereas C5
      halogenation was detrimental. 3-BrCy and 3-ICy were more potent than cytisine at
      evoking [3H]dopamine release from striatal slices (EC50 approximately 11 nM),
      [3H]noradrenaline release from hippocampal slices (EC50 approximately 250 nM),
      increases in intracellular Ca2+ in PC12 cells and inward currents in Xenopus
      oocytes expressing human alpha3beta4 nicotinic receptor (EC50 approximately 2
      microM). These compounds were also more efficacious than cytisine. C3
      halogenation of cytisine is proposed to stabilize the open conformation of the
      nicotinic receptor but does not enhance subtype selectivity.

PMID- 16563373
TI  - 20(S)-ginsenoside Rh2, a newly identified active ingredient of ginseng, inhibits
      NMDA receptors in cultured rat hippocampal neurons.
AB  - Most herbal medicines that are orally administrated have been known to be
      metabolized before they are absorbed from the gastrointestinal tract. We,
      therefore, examined the effects of 20(S)-ginsenosides Rb1, Rg1 and Rg3, the three
      most commonly studied ginsenosides in the central nervous system, and their main
      metabolites on NMDA receptors using fura-2-based digital imaging and perforated
      whole-cell patch-clamp techniques. Among the nine ginsenosides tested, 20(S)
      ginsenoside Rh2 (20(S)-Rh2) along with 20(S)-ginsenoside Rg3 (20(S)-Rg3) produced
      the highest inhibitory effect in cultured hippocampal neurons. Although 20(S)-Rg3
      and 20(S)-Rh2 selectively targeted NMDA receptors with similar potency, they
      produced additive effects and seemed to modulate different NMDA receptor
      regulatory sites. As a competitive antagonist, 20(S)-Rh2 seems to inhibit the
      receptor via its interaction with polyamine-binding sites, and 20(S)-Rg3 does so
      using glycine-binding sites. Therefore, these results suggest that the treatment
      of 20(S)-Rh2, a newly identified active ingredient of ginseng, might be a novel
      preventive candidate in treating neurodegenerative disorders.

PMID- 16563374
TI  - Effects of dextrorotatory morphinans on alpha3beta4 nicotinic acetylcholine
      receptors expressed in Xenopus oocytes.
AB  - We previously demonstrated that dextromethorphan (DM; 3-methoxy-17
      methylmorphinan) analogs have neuroprotective effects, and a recent report showed
      that DM reduces the adverse effects of morphine and blocks alpha3beta4 nicotinic
      acetylcholine receptors, a major target of anti-addictive agents. Here, we
      investigated the effects of DM, three of its analogs (DF, 3-methyl-17
      methylmorphinan; AM, 3-allyloxy-17-methoxymorphian; and CM, 3-cyclopropyl-17
      methoxymorphinan) and one of its metabolites (HM; 3-methoxymorphinan), on
      neuronal alpha3beta4 nicotinic acetylcholine receptor channel activity expressed
      in Xenopus laevis oocytes, using the two-microelectrode voltage clamp technique.
      We found that intraoocyte injection of neuronal alpha3 and beta4 nicotinic
      acetylcholine receptor subunit cRNAs elicited an inward current (IACh) in the
      presence of acetylcholine. Co-treatment with DM, DF, AM, CM or HM inhibited IACh
      in a dose-dependent, voltage-independent and reversible manner. The IC50 values
      for DM, DF, AM, CM and HM were 19.5+/-5.2, 15.8+/-4.5, 16.3+/-1.7, 10.1+/-2.8,
      and 13.5+/-4.0 microM, respectively. The order of potency for the inhibition of
      IACh was CM>HM>DF=AM>DM in oocytes expressing alpha3beta4 nicotinic acetylcholine
      receptors. The inhibitions of (IACh) by DM, DF and HM, AM and CM were non
      competitive. These results indicate that AM, CM and HM could be novel non
      competitive agents regulating alpha3beta4 nicotinic acetylcholine receptor
      channel activity.

PMID- 16563375
TI  - Mallory body (cytokeratin aggresomes) formation is prevented in vitro by p38
      inhibitor.
AB  - Microarray analysis of livers from mice fed diethyl-1,4-dihydro-2,4,6-trimethyl
      3,5-pyridinedicarboxylate (DDC) to induce Mallory body (MB) cytokeratin aggresome
      formation showed that gene expression for cellular adhesion molecules,
      cytokeratins, kinases and aggresome forming proteins were upregulated, when MBs
      were formed in vivo. This response was enhanced when the DDC was refed (mice fed
      DDC for 10 weeks followed by DDC withdrawal for 1 month, then refed DDC for 7
      days). Immunofluorescent antibody staining of the MBs that formed showed that
      MAPK p38 was colocalized with ubiquitin and p62 in the MBs. To investigate
      further the mechanisms of MB formation, primary cultures derived from DDC primed
      mice and their controls were incubated for 6 days. Liver cells cultured for 3 h
      and 6 days were used for microarray analysis. At 3 h, there were no MBs formed,
      but MBs were numerous after 6 days of culture. At 3 h, the expression of a large
      number of genes was different when the control, and the DDC primed hepatocytes
      were compared, which indicates that the primed hepatocytes were phenotypically
      changed. The gene expression of many kinases including p38 was upregulated after
      6 days where the gene expression of cytokeratins, adhesion molecules and
      aggresome forming proteins were upregulated when MBs formed. An inhibitor of p38
      phosphorylation (SB202190) completely prevented MB formation. Western blot showed
      that phosphorylated p38 MAPK and total p38 were absent in vitro after the p38
      inhibitor treatment. Immunostaining of 6-day DDC-primed hepatocyte cultures
      stained with antibodies to p62 and phospho-p38 MAPK showed that phosphorylated
      p38 MAPK was concentrated within the MBs. Antibodies to specific serine
      phosphorylated sites 73 and 431, located in cytokeratin 8, localized to Mallory
      bodies in vivo, indicating that cytokeratin 8 was hyperphosphorylated. The data
      supported the concept that MBs form as the result of hyperphosphorylation of
      cytokeratin 8 by p38.

PMID- 16563376
TI  - Reconstitution of recycling from the phagosomal compartment in streptolysin O
      permeabilized macrophages: role of Rab11.
AB  - By phagocytosis, macrophages engulf large particles, microorganisms and senescent
      cells in vesicles called phagosomes. Many internalized proteins rapidly shuttle
      back to the plasma membrane following phagosome biogenesis. Here, we report a new
      approach to the study of recycling from the phagosomal compartment: streptolysin
      O- (SLO) permeabilized macrophages. In this semi-intact cell system, energy and
      cytosol are required to efficiently reconstitute recycling transport. Addition of
      GDPbetaS strongly inhibits this transport step, suggesting that a GTP-binding
      protein modulates the dynamics of cargo exit from the phagosomal compartment.
      GTPases of the Rab family control vesicular trafficking, and Rab11 is involved in
      transferrin receptor recycling. To unravel the role of Rab11 in the phagocytic
      pathway, we added recombinant proteins to SLO-permeabilized macrophages.
      Rab11:S25N, a negative mutant, strongly diminishes the release of recycled
      proteins from phagosomes. In contrast, wild type Rab11 and its positive mutant
      (Rab11:Q70L) favor this vesicular transport event. Using biochemical and
      morphological assays, we confirm that overexpression of Rab11:S25N substantially
      decreases recycling from phagosomes in intact cells. These findings show the
      requirement of a functional Rab11 for the retrieval to the plasma membrane of
      phagosomal content. SLO-permeabilized macrophages likely constitute a useful tool
      to identify new molecules involved in regulating transport along the phagocytic
      pathway.

PMID- 16563377
TI  - Fas-ligand is stored in secretory lysosomes of ocular barrier epithelia and
      released with microvesicles.
AB  - Previously we described the release of hr44 from the ciliary epithelium to
      coincide with the loss of the late endosomal/lysosomal marker protein CD63 in
      mildly inflamed rat eyes. We showed that both proteins are released with
      microvesicles into the supernatant of cultured retinal pigmented epithelial cells
      (ARPE-19). Here we wish to determine whether there is a concomitant loss of fas
      ligand (FasL) in vivo and whether ocular epithelial cells have secretory
      lysosomes similar to T cells, from where FasL and hr44 could derive. FasL plays
      an important role in immunity, immune cell homeostasis and in the maintenance of
      immune privilege in the eye. However the mode of release of FasL from ocular
      epithelial cells or its activity in the eye is not fully understood. In normal
      rat eyes, FasL was detected in the epithelia of the iris and ciliary body and in
      the anterior region of the retinal pigmented epithelium. FasL is expressed
      constitutively and is associated with vesicular structures in the normal ciliary
      epithelium but is not detectable in the ciliary epithelium of inflamed eyes. In
      contrast, the posterior RPE, which under normal conditions is negative for FasL
      and hr44 showed strong staining for both molecules in areas adjacent to sub
      retinal inflammatory infiltrates. Immunofluorescence and Western blot analysis
      indicated that cultured ARPE-19 cells express both the soluble and membrane form
      of FasL. The intracellular concentration of FasL was significantly increased in
      cells grown in presence of interferon (INF)-gamma. The microvesicles released by
      cultured ARPE-19 cells and previously shown to be positive for hr44 and CD63 are
      also positive for membrane FasL. Expression of a recombinant fluorescent
      construct of FasL together with immuno-staining for CD63 demonstrated that FasL
      localises to the endocytic compartment of ARPE-19 cells and of melanoma cells
      (positive control). In cells with lysosomes devoid of specialised secretory
      functions (e g. HeLa cells) recombinant FasL localised to the cell membrane,
      demonstrating that RPE cells have secretory lysosomes. We suggest that ocular
      epithelial cells release soluble FasL and the membrane form of FasL with
      vesicles. Both forms may contribute in different ways to the effectiveness of the
      ocular immune response and immune privilege.

PMID- 16563379
TI  - Focus on molecules: rod cGMP phosphodiesterase type 6.

PMID- 16563378
TI  - In vivo reactivation of a quiescent cell population located in the ocular ciliary
      body of adult mammals.
AB  - Rare quiescent cells with stem cell characteristics have been isolated from the
      ocular ciliary body (CB) of adult mammals. In vitro, adult retinal stem cells
      were reported to generate sphere colonies containing multipotent retinal
      progenitor cells. Whether proliferation of this stem cell population can be
      stimulated in vivo in order to generate new retinal cells is an important issue.
      Herein we report on the in vivo reactivation of a quiescent cell population
      present in the CB upon growth factors (GF) stimulation. GF stimulation resulted
      in the re-acquisition of embryonic characteristics (Nestin) and expression of the
      cell cycle entry markers CyclinD1 and Ki67 by a subset of CB epithelial cells.
      This inductive effect was not observed in the neural retina. GF-activated CB
      epithelial cells co-express the retinal progenitor homeodomain transcription
      factors Pax6 and Chx10. Serial GF injections led to do novo proliferation of
      clusters of cells in the CB, in a dose-dependent manner, as revealed by
      bromodeoxyuridine (BrdU) incorporation. Analysis of cells' BrdU content within
      individual clusters suggests a mode of cell division that is predominantly
      asymmetric. Cell proliferation was not induced by CB or retinal damage, as
      indicated by the absence of TUNEL-labeled cells. Newly produced cells did not
      migrate into the retina nor did they differentiate into retinal neurons. This
      study demonstrates that proliferation of a quiescent cell population with retinal
      stem/progenitor cell characteristics can be reactivated in vivo upon GF
      injections and suggests that, in adult mammals, the CB is a non-permissive
      environment for cell migration and neurogenesis.

PMID- 16563380
TI  - Transforming growth factor beta2-induced myofibroblastic differentiation of human
      retinal pigment epithelial cells: regulation by extracellular matrix proteins and
      hepatocyte growth factor.
AB  - Retinal pigment epithelial (RPE) cells possess the potential to
      transdifferentiate into myofibroblasts after stimulation with transforming growth
      factor beta (TGFbeta) and are implicated in the pathogenesis of proliferative
      vitreoretinopathy. In this study we evaluated how TGFbeta2 and various
      extracellular matrix (ECM) proteins modulate the transdifferentiation of human
      fetal retinal pigment epithelial cells (RPE) cells into myofibroblast-like cells.
      Furthermore, we investigated whether hepatocyte growth factor (HGF) can suppress
      this transdifferentiation. RPE cells were cultured on ECM coated or uncoated
      surfaces in the presence or absence of TGFbeta2. HGF was added to certain
      cultures only once or on a daily basis during the treatment. Transdifferentiation
      of RPE cells into myofibroblasts was assessed by the quantitation of alpha-smooth
      muscle actin (alpha-SMA) using immunocytochemistry, flow cytometry, real-time PCR
      and Western blotting. TGFbeta2 induced a significant increase of alpha-SMA
      expression in a dose-dependent manner. Compared with growth on uncoated surfaces,
      RPE cultured on fibronectin (FN)-coated surfaces and stimulated with TGFbeta2
      showed a significantly higher alpha-SMA expression than untreated cells. This
      upregulation of alpha-SMA could be markedly reduced by daily treatment with HGF;
      however, a single HGF administration did not significantly reduce alpha-SMA.
      These findings are important for further understanding the interaction of
      cytokines, RPE cells and their environment in mesenchymal transformation as well
      as its possible modulation. Continuous or long-term treatment with HGF should be
      further investigated for its potential to prevent mesenchymal
      transdifferentiation of RPE cells, and ultimately, PVR in vivo.

PMID- 16563381
TI  - Focus on molecules: the aryl hydrocarbon receptor interacting protein-like 1
      (AIPL1).

PMID- 16563382
TI  - Focus on molecules: glial fibrillary acidic protein (GFAP).

PMID- 16563383
TI  - Melatoninergic differentiation of retinal photoreceptors: activation of the
      chicken hydroxyindole-O-methyltransferase promoter requires a homeodomain-binding
      element that interacts with Otx2.
AB  - The gene encoding the last enzyme of the melatonin-synthesis pathway,
      hydroxyindole-O-methyltransferase (HIOMT), is selectively expressed in retinal
      photoreceptors and pineal cells. Here, we analysed the promoter of the chicken
      HIOMT gene and we found that a homeodomain-binding element located in the
      proximal region of this promoter was essential for its activation in primary
      cultures of embryonic chicken retinal cells. This homeodomain-regulatory element
      interacted with a protein expressed in the chicken retina and pineal gland, which
      was recognized by an anti-Otx2 antiserum. Recombinant Otx2 expressed in vitro was
      able to bind this DNA element and to directly transactivate the chicken HIOMT
      promoter. This promoter was also transactivated by another member of the Otx
      family, Otx5, but the amplitude of stimulation was lower than with Otx2. The
      spatio-temporal pattern of Otx2 expression was compatible with a possible role of
      this transcription factor in HIOMT gene activation. In adult chicken, Otx2 mRNA
      was found to be present in those two tissues that express HIOMT: the retina and
      the pineal gland. During development, a burst of Otx2 mRNA closely matched the
      timing of HIOMT gene activation in these two tissues. In the pineal, Otx2
      immunolabelling was specifically localized in the nuclei of photoreceptor cells.
      In the neural retina, Otx2 immunoreactivity brightly decorated the photoreceptor
      nuclei and extended more faintly to the outer half of the inner nuclear layer.
      Together, the data support a role of Otx2 in the onset of HIOMT expression in
      developing chicken photoreceptors.

PMID- 16563384
TI  - Focus on molecules: the OPA1 protein.

PMID- 16563385
TI  - Focus on molecules: Pax-6, the eye master.

PMID- 16563386
TI  - Trypanosoma brucei: composition, organisation, plasticity, and differential
      transcription of NlaIII repeat elements in drug-resistant and sensitive isolates.
AB  - A Trypanosoma brucei brucei DNA repeat sequence termed NlaIII repeat (NR) was
      originally isolated from a multidrug-resistant field isolate CP547 [Jamnadass,
      R., 1995. Identification and characterisation of an extrachromosomal element from
      a multidrug-resistant isolate of T. brucei brucei, Ph.D. thesis, Brunel
      University, UK]. Subsequently studied in a laboratory strain (Tb427) [Alsford,
      N.S., Navarro, M., Jamnadass, H.R., Dunbar, H., Ackroyd, M., Murphy, N.B., Gull,
      K., Ersfeld,K., 2003. The identification of circular extrachromosomal DNA in the
      nuclear genome of T. brucei. Molecular Microbiology 47, 277-288], NRs were
      exclusively episomal. Here we show that NR sequences in CP547 are present on
      linear chromosomes as well as on episomal circular elements. Sequence analysis
      shows that NRs are composed of three classes of sub-repeat arranged in a specific
      order. Heterogeneity in size and sequence of an episomal 6.6kbp element was shown
      in successive passages of the original CP547 isolate and derived clones in mice.
      Its copy number was unstable and was affected by selective pressure with the
      trypanocide diminazene aceturate. Some of the extrachromosomal elements appear to
      be composed of RNA-DNA hybrids. NR sequences were transcribed in a
      developmentally regulated manner but transcripts did not contain the spliced
      leader sequence found on all trypanosome mRNAs.

PMID- 16563387
TI  - Setting the biological time in central and peripheral clocks during ontogenesis.
AB  - In mammals, the principal circadian clock within the suprachiasmatic nucleus
      (SCN) entrains the phase of clocks in numerous peripheral tissues and controls
      the rhythmicity in various body functions. During ontogenesis, the molecular
      mechanism responsible for generating circadian rhythmicity develops gradually
      from the prenatal to the postnatal period. In the beginning, the maternal signals
      set the phase of the newly developing fetal and early postnatal clocks, whereas
      the external light-dark cycle starts to entrain the clocks only later. This
      minireview discusses the complexity of signaling pathways from mothers and the
      outside world to the fetal and newborn animals' circadian clocks.

PMID- 16563388
TI  - The interplay between virus infection and the cellular RNA interference
      machinery.
AB  - RNA interference (RNAi) plays a pivotal role in the regulation of gene expression
      to control cell development and differentiation. In plants, insects and nematodes
      RNAi also functions as an innate defence response against viruses. Similarly,
      there is accumulating evidence that RNAi functions as an antiviral defence
      mechanism in mammalian cells. Viruses have evolved highly sophisticated
      mechanisms for interacting with the host cell machinery, and recent evidence
      indicates that this also involves RNAi pathways. The cellular RNAi machinery can
      inhibit virus replication, but viruses may also exploit the RNAi machinery for
      their own replication. In addition, viruses can encode proteins or RNA molecules
      that suppress existing RNAi pathways or trigger the silencing of specific host
      genes. Besides the natural interplay between RNAi and viruses, induced RNAi
      provides an attractive therapy approach for the fight against human pathogenic
      viruses. Here, we summarize the latest news on virus-RNAi interactions and RNAi
      based antiviral therapy.

PMID- 16563389
TI  - A short motif in the C-terminus of mouse bestrophin 3 [corrected] inhibits its
      activation as a Cl channel.
AB  - Bestrophins are a new family of anion channels. Here, we examined the Cl channel
      activity of mBest4. Surprisingly, wild type mouse bestrophin-4 (mBest4) did not
      induce functional Cl channels when over-expressed in HEK293 cells. However,
      deletion of part of the C-terminus (residues 353-669) produced large Cl currents,
      suggesting the presence of a C-terminal motif that inhibited Cl channel function.
      Deletion of a short motif (356-364) or substitution of certain residues in this
      motif with alanines also resulted in expression of robust Cl currents. The
      channel activity of the mBest4 protein lacking the C-terminus (residues 353-669)
      was specifically inhibited by co-expression of C-terminal fragments of mBest4
      having the inhibitory motif, suggesting that the C-terminal motif blocked mBest4
      channel activity probably by interacting with the channel pore.

PMID- 16563390
TI  - Phosphoinositide-dependent kinase l (PDK1) haplo-insufficiency inhibits
      production of alpha/beta (alpha/beta) but not gamma delta (gamma/delta) T
      lymphocytes.
AB  - In the present study, we have explored the impact of deleting a single allele of
      PDK1 in T cell progenitors on alpha/beta and gamma/delta T cell development. The
      data show that deleting a single allele of PDK1 allows differentiation of
      alpha/beta T cells but prevents their proliferative expansion in the thymus.
      Accordingly, mice with T cells that are haplo-insufficient for PDK1 have reduced
      numbers of thymocytes and alpha/beta peripheral T cells. T cell progenitors also
      give rise to gamma/delta T cells but in contrast to the loss of alpha/beta T
      cells in T-PDK1 null and haplo-insufficient mice, there were increased numbers of
      gamma/delta T cells. The production of alpha/beta T cells is dependent on the
      proliferative expansion of thymocytes and is determined by a balance between the
      frequency with which cells enter the proliferative phase of the cell cycle and
      rates of cell death. Herein, we show that PDK1 haplo-insufficient thymocytes have
      no defects in their ability to enter the cell cycle but show increased apoptosis.
      PDK1 thus plays a determining role in the development of alpha/beta T lymphocytes
      but does not limit gamma/delta T cell development.

PMID- 16563391
TI  - Catalytic folding of the Cepsilon3 domain by its high affinity receptor.
AB  - The interaction of immunoglobulin E (IgE) with its cellular receptor
      FcepsilonRIalpha is a central regulator of allergy. Structural studies have
      identified the third domain (Cepsilon3) of the constant region of epsilon heavy
      chain as the receptor binding region. The isolated Cepsilon3 domain is a "molten
      globule" that becomes structured upon binding of the FcepsilonRIalpha ligand. In
      this study, fluorescence and nuclear magnetic resonance spectroscopies are used
      to characterise the role of soluble FcepsilonRIalpha in the folding of the
      monomeric Cepsilon3 domain of IgE. Soluble FcepsilonRIalpha is shown to display
      characteristic properties of a catalyst for the folding of Cepsilon3, with the
      rate of Cepsilon3 folding being dependent on the concentration of the receptor.

PMID- 16563392
TI  - Hepatic guanylate cyclase activity is decreased in a model of cirrhosis: a
      quantitative cytochemistry study.
AB  - The production of nitric oxide (NO) in liver disease and its role in vascular
      control has been a subject of much interest in recent years. However, the
      activity of guanylate cyclase (GC), the enzyme activated by NO has received
      little attention with regard to liver disease. In this study we have utilised a
      quantitative cytochemical technique to examine the activity of GC on a per cell
      basis in a rat model of cirrhosis. Our results show a significant reduction in GC
      activity, indicating that vascular regulation is likely to be substantially
      affected irrespective of NO generation in this disease model.

PMID- 16563393
TI  - Inhibition of cytochrome p450 brain aromatase reduces two male specific sexual
      behaviours in the male Endler guppy (Poecilia reticulata).
AB  - In mammalian and avian vertebrate groups, androgens act as controlling agents on
      male aggression and courtship behaviour by their conversion to oestrogens by
      cytochrome P450 aromatase in well-defined brain regions. Despite the fact that
      bony fishes have exceptionally high brain aromatase activity, little is known
      about it's possible regulatory effects on the reproductive behaviours of
      teleosts. In this study, Endler guppy males (Poecilia reticulata) were subjected
      to 26-29 days of 24-h exposure to two different concentrations (15 and 100
      microg/L) of the aromatase inhibitor fadrozole in the water. Compared with the
      control males, two of three courtship activities in males exposed to the higher
      concentration were reduced when they were paired with receptive stimulus females.
      Reduction in brain aromatase activity was confirmed in both exposed groups with
      the use of the tritiated water assay.

PMID- 16563394
TI  - Complete versus incomplete placenta previa and obstetric outcome.
AB  - OBJECTIVE: To compare obstetric outcome in women with complete versus incomplete
      placenta previa (PP). METHODS: A 10-year retrospective case-control study was
      conducted between 1992 and 2001. A 202 singleton pregnancies with PP were
      analyzed. RESULTS: The incidence of PP was 0.4%. Complete PP comprised 32.7% and
      incomplete PP 67.3% of cases. No difference was observed in the frequency of
      antepartum hemorrhage. Women with complete PP had significantly higher
      requirement for antepartum and postpartum transfusions, higher frequency of
      postpartum hemorrhage and postpartum hysterectomy. The risk for placenta accreta
      was increased in complete PP group even after controlling for confounding factors
      (adjusted OR=3.75, 95% CI=1.11-12.68, p<0.05). No difference in the frequency of
      preterm delivery was found between the groups. Term infants of mothers with
      complete PP had significantly lower birth weight (3205 vs. 3360, p=0.04).
      CONCLUSION: Complete PP is a high-risk subgroup of PP associated with higher
      maternal morbidity in comparison to incomplete PP.

PMID- 16563395
TI  - Prognostic factors in node-positive patients with stage IB-IIB cervical cancer
      treated by radical hysterectomy and pelvic lymphadenectomy.
AB  - OBJECTIVE: The purpose of the present study was to identify prognostic factors in
      surgically treated patients with stage IB-IIB cervical cancers, who also
      presented with positive pelvic nodes. METHOD: The patient population consisted of
      68 individuals presenting with stage IB-IIB cervical cancers and with
      histologically proven pelvic lymph nodes. RESULT: We found no association between
      the type of adjuvant therapy and patient outcome. Multivariate analysis revealed
      that non-squamous histology was an independent prognostic factor for disease-free
      and overall survival rates. In squamous cell carcinomas, the bilateral nature of
      the positive nodes was found to be a significant factor for disease-free survival
      rates. In non-squamous cell carcinomas, positive nodes of more than 2 cm in size
      were found to be a significant factor for disease-free survival rates.
      CONCLUSION: Non-squamous histology was an independent prognostic factor and
      chemoradiotherapy did not improve the survival outcomes of the patients in this
      study population.

PMID- 16563396
TI  - Laparoscopic technology for the treatment of endometrial cancer.

PMID- 16563397
TI  - Sickle cell disease and pregnancy in Bahrain.
AB  - OBJECTIVE: To determine the morbidity and outcome of pregnancies complicated by
      homozygous sickle cell disease (SCD) in Bahrain. METHODS: A controlled study was
      conducted of all the pregnancies of women with SCD who were delivered at
      Salmaniya Medical Complex and affiliate hospitals in Bahrain between January 1,
      1998, and December 31, 2002. RESULTS: There were 351 pregnancies with SCD, giving
      an incidence of 0.67%. The mean+/-S.D. age of women with SCD was 28.8+/-5.7
      years. These women, who were mostly from Shia villages, had more spontaneous
      abortions than the 351 controls (32% and 12%, respectively). Compared with the
      control group, the mean+/-S.D. number of pregnancies among women with SCD was
      5.0+/-1.9 vs. 5.7+/-3.1; birth weight, 2,965+/-540 g vs. 3,457+/-497 g; rate of
      preterm deliveries, 25.9% vs. 12%; incidence of intrauterine growth restriction,
      10% to 13% vs. 4% to 7%; Apgar scores at 1 and 10 min, 8.1+/-0.8 and 8.8+/-0.8;
      and cesarean section rate, 19.0% vs. 12.7%. There were no differences in the
      rates of pre-eclampsia, antepartum and postpartum hemorrhage, or stillbirth.
      There were 4 maternal deaths directly related to SCD complications. Hemoglobin
      analysis was performed in 86% of the women with SCD. Of these women, 60.6% had
      homozygous SCD with raised levels of fetal hemoglobin (more than 5% HbF); 9.6%
      had sickle cell hemoglobin with beta-thalassemia disease; and 1.4% had sickle
      cell hemoglobin only. Vaso-occlusive crises were the most common cause of
      hospital admissions during pregnancy (42.2%), while hemolytic and sequestration
      crises accounted for 28.0% and 0.6% of admissions. CONCLUSION: Mortality,
      morbidity, and perinatal loss are still considerable among women with SCD in
      Bahrain. To reduce mortality and morbidity, there is a need for a
      multidisciplinary team able to deal with pregnancy complications due to SCD.

PMID- 16563399
TI  - CETP levels rather than polymorphisms as markers of coronary risk: healthy
      athlete with high HDL-C and coronary disease--effectiveness of probucol.

PMID- 16563398
TI  - Evaluation of an educational "toolbox" for improving nursing staff competence and
      psychosocial work environment in elderly care: results of a prospective, non
      randomized controlled intervention.
AB  - BACKGROUND: Lack of professional development opportunities among nursing staff is
      a major concern in elderly care and has been associated with work dissatisfaction
      and staff turnover. There is a lack of prospective, controlled studies evaluating
      the effects of educational interventions on nursing competence and work
      satisfaction. OBJECTIVES: The aim of this study was to evaluate the possible
      effects of an educational "toolbox" intervention on nursing staff ratings of
      their competence, psychosocial work environment and overall work satisfaction.
      DESIGN: The study was a prospective, non-randomized, controlled intervention.
      PARTICIPANTS AND SETTINGS: Nursing staff in two municipal elderly care
      organizations in western Sweden. METHODS: In an initial questionnaire survey,
      nursing staff in the intervention municipality described several areas in which
      they felt a need for competence development. Measurement instruments and
      educational materials for improving staff knowledge and work practices were then
      collated by researchers and managers in a "toolbox." Nursing staff ratings of
      their competence and work were measured pre and post-intervention by
      questionnaire. Staff ratings in the intervention municipality were compared to
      staff ratings in the reference municipality, where no toolbox was introduced.
      RESULTS: Nursing staff ratings of their competence and psychosocial work
      environment, including overall work satisfaction, improved significantly over
      time in the intervention municipality, compared to the reference group. Both
      competence and work environment ratings were largely unchanged among reference
      municipality staff. Multivariate analysis revealed a significant interaction
      effect between municipalities over time for nursing staff ratings of
      participation, leadership, performance feedback and skills' development. Staff
      ratings for these four scales improved significantly in the intervention
      municipality as compared to the reference municipality. CONCLUSIONS: Compared to
      a reference municipality, nursing staff ratings of their competence and the
      psychosocial work environment improved in the municipality where the toolbox was
      introduced.

PMID- 16563400
TI  - Metabolic syndrome and urinary cGMP excretion in general population.
AB  - To examine the relationship between metabolic syndrome and endothelial
      dysfunction, we investigated cross-sectionally the correlation between metabolic
      risk factors and urinary excretion of cyclic guanosine 3',5'-monophosphate
      (cGMP), a second messenger of nitric oxide (NO), in 1541 Japanese men and women
      aged 40-79 years. The 24-h urinary excretion of cGMP was measured using a (125)I
      labeled cGMP radioimmunoassay and was adjusted for urinary creatinine excretion
      (nmol/mmol creatinine). The components of metabolic syndrome were defined based
      on the following criteria: body mass index (BMI)> or =25.0 kg/m(2), fasting
      plasma glucose> or =6.11 mmol/l or non-fasting plasma glucose level> or =11.1
      mmol/l, systolic blood pressure> or =130 mm Hg or diastolic blood pressure> or
      =85 mm Hg, high-density lipoprotein (HDL)-cholesterol<1.03 mmol/l for men and
      <1.29 mmol/l for women, and triglyceride> or =1.69 mmol/l. The number of
      components of metabolic syndrome correlated inversely with urinary cGMP
      excretion; means of cGMP excretion for the whole group adjusted for age, sex, and
      cardiovascular risk factors were 53.6, 48.6, 47.9, 44.4 and 42.3 nmol/mmol for 0,
      1, 2, 3, and 4-5 components of metabolic syndrome, respectively (p=0.002). Our
      data suggest that a reduction of NO bioactivity concur with clustered features of
      the metabolic syndrome.

PMID- 16563401
TI  - Doxycycline affects diet- and bacteria-associated atherosclerosis in an ApoE
      heterozygote murine model: cytokine profiling implications.
AB  - BACKGROUND: It has been postulated that systemic infection with pathogens such as
      Porphyromonas gingivalis (Pg) elevates the inflammatory response and increases
      susceptibility to atherosclerosis. We hypothesized that Doxycycline would be
      beneficial in diet- and/or Pg-induced atherosclerosis given its role in various
      cell functions and matrix remodeling. METHODS AND RESULTS: ApoE+/- mice were
      inoculated weekly with Pg and treated with either Doxycycline or saline; animals
      were fed either a high-fat or chow diet. Animals were euthanized at 14 or 24
      weeks and histomorphometric analysis of atheromatous lesions in proximal aorta,
      levels of SAA and serum cytokine profiling were performed. Histomorphometric
      analysis demonstrated that in non-infected mice fed a high fat diet, Doxycycline
      treatment resulted in a reduction of mean lesions from 10.5%+/-.49 to 1.09%+/
      0.102 (p<0.05) at 14 weeks and a reduction from 21.5%+/-6.49 to 8.26%+/-0.162
      (p=0.106) at 24 weeks. Chow-fed Pg mice treated with Doxyclycline also resulted
      in a reduction from 0.62%+/-0.128 to 0.0%+/-0.0 (p<0.05) at 14 weeks and a
      reduction from 0.92%+/-0.23 to 0.0%+/-0.0 (p<0.05) at 24 weeks. Administration of
      Doxycycline to mice fed a high fat diet and Pg-inoculated resulted in a reduction
      of mean percentage of atheromatous lesions from 16.46%+/-1.69 to 1.141%+/-0.23
      (p<0.05) at 14 weeks and a reduction from 25.27%+/-1.734 to 0.428%+/-0.033
      (p<0.05) at 24 weeks. At this timepoint, SAA levels in Pg-infected animals were
      reduced by five-fold and three-fold in Doxycycline-treated chow and high fat-diet
      groups, respectively. Cytokine antibody arrays revealed a marked reduction in the
      levels of pro-inflammatory cytokines in Doxycycline-treated groups whether Pg
      infected or fed a high fat diet while anti-inflammatory cytokines were not
      affected. Consistent with the role of Doxycycline on matrix proteases, at 24
      weeks MMP-9 Serum levels were markedly reduced by 60% (p<0.05) and 30% (p<0.05)
      with Doxycycline treatment in Pg-infected high fat and chow diet groups,
      respectively. CONCLUSIONS: Doxycycline decreases pro-inflammatory cytokines and
      results in reduction of atherosclerosis in ApoE+/-Pg-inoculated and/or high fat
      diet fed mice.

PMID- 16563402
TI  - Anisotropic Poisson's ratio and compression modulus of cortical bone determined
      by speckle interferometry.
AB  - Young's modulus and Poisson's ratios of 6mm-sized cubes of equine cortical bone
      were measured in compression using a micro-mechanical loading device. Surface
      displacements were determined by electronic speckle pattern-correlation
      interferometry. This method allows for non-destructive testing of very small
      samples in water. Analyses of standard materials showed that the method is
      accurate and precise for determining both Young's modulus and Poisson's ratio.
      Material properties were determined concurrently in three orthogonal anatomic
      directions (axial, radial and transverse). Young's modulus values were found to
      be anisotropic and consistent with values of equine cortical bone reported in the
      literature. Poisson's ratios were also found to be anisotropic, but lower than
      those previously reported. Poisson's ratios for the radial-transverse and
      transverse-radial directions were 0.15+/-0.02, for the axial-transverse and axial
      radial directions 0.19+/-0.04, and for the transverse-axial and radial-axial
      direction 0.09+/-0.02 (mean+/-SD). Cubes located only millimetres apart had
      significantly different elastic properties, showing that significant spatial
      variation occurs in equine cortical bone.

PMID- 16563403
TI  - Liquid chromatograpic-mass spectrometric analysis of phenolics and free radical
      scavenging activity of rosemary extract from different raw material.
AB  - The antioxidant activity of rosemary (Rosmarinus officinalis) extract from
      different raw materials has been studied. Extracts were prepared from wild or
      drip-irrigated plants, as well as from the by-product resulting from the
      distillation of the aromatic essential oil. The radical scavenging activity of
      rosemary extracts was compared with that of antioxidants widely used in food,
      such as BHT and delta-tocopherol, using an optimization of the method based on
      the reduction of the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The results
      pointed the excellent antioxidant activity of the crude fresh rosemary extracts,
      which was almost identical to that of pure delta-tocopherol, and higher than that
      of BHT; extracts prepared from distilled rosemary showed the lowest activity,
      although they are also of interest due to the low cost of the raw material. High
      performance liquid chromatography (HPLC) combined with diode array (DAD) and
      electrospray (ESI)-ion trap-MS detection was used to separate and identify the
      compounds present in the rosemary extracts. Rosmarinic acid, carnosic acid and
      seven of their terpene-type metabolites, and seven flavones were identified. The
      drying and/or distillation treatments used with the plant material strongly
      affected the content of the two compounds of higher antioxidant activity:
      rosmarinic acid and carnosic acid.

PMID- 16563404
TI  - Characterization of hemoglobin Wurzburg (alpha2beta2 4(A1)Thr-->Asn), a new
      electrophoretically silent variant, by mass spectrometry and molecular modeling
      studies.
AB  - The first hemoglobin (Hb) variant carrying a mutation at beta4 was identified as
      beta4(A1)Thr-->Asn or Hb Wurzburg and constituted 38% of the total hemoglobin. It
      showed a slightly elevated oxygen affinity and a slightly decreased cooperativity
      index (n50 = 2.3 versus n50 = 2.8). The analysis of the electrostatic potential
      showed an increased negative charge at the site of the mutation with a
      displacement of beta6(A3)Glu by 1.3A. The replacement of threonine by asparagine
      seems to stabilize the R conformation. This may explain partially both the high
      affinity and the reduction in cooperativity.

PMID- 16563405
TI  - Characterization of quantum dot bioconjugates by capillary electrophoresis with
      laser-induced fluorescent detection.
AB  - In this paper, we present a universal, highly efficient and sensitive method for
      the characterization of quantum dot (QD) bioconjugates based on capillary
      electrophoresis with laser-induced fluorescent (LIF) detection. We first prepared
      CdTe QDs in aqueous phase by a chemical route with mercaptopropionic acid as a
      ligand, and then were coupled to certain proteins using bifunctional linkage
      reagent or electrostatic attraction. The QD bioconjugates were characterized by
      capillary electrophoresis with LIF detection. We found that QD bioconjugates were
      efficiently separated with free QDs by the optimization of buffer pH.
      Furthermore, we found that ultrafiltration was an effective and simple approach
      to purify QD conjugates with bovine serum albumin (BSA). Due to their broad
      absorption spectra and size dependent emission wavelength tunability, QDs can be
      excited to emit different colour fluorescence using a single wavelength laser
      source, and therefore, we believe that CE with LIF detection will become a
      universal and efficient tool for the characterization of QD bioconjugates.

PMID- 16563406
TI  - Improvement of proline chiral stationary phases by varying peptide length and
      linker.
AB  - Seven new stationary phases with different number of proline units and/or
      different linkage to silica gel were prepared and evaluated in order to improve
      the performance of proline chiral stationary phases. The average separation
      factor achieved with the 53 analytes increases with the number of proline units
      in the stationary phases. When the proline peptides are directly attached to the
      3-methylaminopropyl silica gel without using the 6-methylaminohexanoic acid
      linker, the stationary phases perform better overall. For decaproline chiral
      stationary phase 8, the separation also depends on the mobile phase system used.
      For this stationary phase, the CH2Cl2/hexanes/2-propanol system significantly
      outperforms the 2-propanol/hexanes system. For the 53 analytes tested, the
      separation factors achieved with this stationary phase compare well with those
      for three commercial columns.

PMID- 16563407
TI  - Levels in the interpretive optimisation of selectivity in high-performance liquid
      chromatography: a magical mystery tour.
AB  - Interpretive approaches for selectivity optimisation, which are those supported
      by retention models, are able to exploit efficiently the capabilities of the
      chromatographic system. The resolution of a mixture is usually faced in a first
      trial by looking for a unique experimental condition, able to resolve all
      compounds in the sample. If this is not possible, the problem can be outlined
      with less ambitious aims, focusing on only some compounds. In an extreme case, a
      single analyte can be individually optimised. Current strategies that give answer
      to the different goals pursued in the analysis, which are classified as total,
      partial and specific, are reviewed. Optimisation oriented to deconvolution,
      useful in case of partial coelution, and robust measurements of resolution, are
      also outlined. The steps recognised in any chromatographic optimisation
      procedure, and some fundamentals and tools used in optimisation approaches for
      isocratic and gradient elution are commented to explain different strategies.
      Examples of increasing complexity are supplied to explain the problematic arose,
      and the convenience in applying a certain methodology. Details on the
      mathematical treatment for each particular optimisation strategy are also given.

PMID- 16563408
TI  - Selective removal of polyethylene or polypropylene from their blends based on
      difference in their adsorption behaviour.
AB  - The adsorption of polyethylene and polypropylene on zeolites depends on the
      nature of zeolite, the solvent as well as the molar mass of the polymer sample.
      For example, linear polyethylene is strongly retained on zeolite SH-300 from
      decalin, while isotactic, syndiotactic or atactic polypropylene is fully eluted
      in this system. On the other hand, polypropylene is retained on zeolite CBV-780
      from diphenylether, while linear polyethylene is eluted. These differences in the
      elution behaviour have been utilised for selective removal of either linear
      polyethylene or polypropylene from blends of both polymers. The desorption of the
      retained polymer is difficult, or at times impossible. However, the selected
      adsorption systems have complimentary character, i.e. either one or second
      component is eluted or fully retained. Thus these sorbent/solvent systems,
      identified herein, are the first isocratic chromatographic systems, which enable
      selectively to remove polyethylene or polypropylene from their mixture. Moreover,
      decalin/SH-300 enables the removal of both linear and branched polyethylene from
      mixtures with random ethylene/propylene copolymers (polyethylene fully retained,
      ethylene/propylene copolymers eluted).

PMID- 16563409
TI  - Adsorptive removal of tannin from aqueous solutions by cationic surfactant
      modified bentonite clay.
AB  - The removal of tannin from aqueous media by cationic surfactant-modified
      bentonite clay was studied in a batch system. The surfactant used was
      hexadecyltrimethylammonium chloride. Adsorbent characterizations were
      investigated using X-ray diffraction, infrared spectroscopy, surface area
      analysis, and potentiometric titration. The effects of pH, contact time, initial
      solute concentration, adsorbent dose, ionic strength, and temperature on the
      adsorption of tannin onto modified clay were investigated. The adsorbent
      exhibited higher tannin removal efficiency (>99.0%) from an initial concentration
      of 10.0 micromol/L at pH 3.0. Adsorption capacity decreased from 90.1 to 51.8%
      with an increase in temperature from 10 to 40 degrees C at an initial
      concentration of 25.0 micromol/L. The adsorption process was found to follow
      pseudo-first-order kinetics. Film diffusion was found to be the rate-limiting
      step. Tannin adsorption was found to decrease with increase in ionic strength.
      The tannin equilibrium adsorption data were fitted to Langmuir and Freundlich
      isotherm models, the former being found to provide the best fit of the
      experimental data. The maximum monolayer adsorption capacity for tannin was 69.80
      micromol/g at 30 degrees C. Comparison of adsorption capacity of the modified
      clay with reported adsorbents in the literature was also presented. Adsorbed
      tannin on modified clay can be recovered by treatment with 0.1 M NaOH solution.
      Regeneration experiments were tried for four cycles and results indicate a
      capacity loss of <10.0%. From the results it can be concluded that the surfactant
      modified clay could be a good adsorbent for treating tannin-contaminated waters.

PMID- 16563410
TI  - Arrangement, conformation, and mobility of surfactant molecules intercalated in
      montmorillonite prepared at different pillaring reagent concentrations as studied
      by solid-state NMR spectroscopy.
AB  - The arrangement, conformation, and mobility of dodecyltrimethylammonium cations
      (DDTMA+) intercalated in montmorillonite prepared with different pillaring
      reagent concentrations have been studied by 13C relaxation time measurement,
      cross-polarization dynamics, and two-dimensional proton wide-line separation (2D
      WISE) spectroscopy, as well as X-ray powder diffraction (XRD). We demonstrate
      that the arrangement of DDTMA+ and the mobility of various groups are different,
      depending on the pillaring concentration, but the conformations of alkyl chains
      are similar. XRD experiments illustrate that at three different pillaring
      concentrations (DDmt0.2, DDmt0.5, and DDmt1.0), the organic cations adopt a
      lateral-monolayer, lateral-monolayer, and pseudotrilayer arrangement,
      respectively. 13C MAS NMR reveals that the alkyl chains at the three
      concentrations uniformly display a large amount of mixed trans and gauch
      conformation (disordered) and a small amount of trans conformation (ordered). 13C
      spin-lattice relaxation time and 1H-13C cross-polarization dynamics measurement,
      along with 2D WISE NMR experiments, indicate that the mobility is much different
      for various groups at a given concentration and for a given group at different
      concentrations. At each concentration N-methyl unusually possesses the highest
      mobility, even exceeding that of the terminal methyl; at different concentrations
      the N-methyl and terminal methyl in DDmt1.0 exhibit the highest mobility compared
      with the other two samples.

PMID- 16563411
TI  - Manufacture of large uniform droplets using rotating membrane emulsification.
AB  - A new rotating membrane emulsification system using a stainless steel membrane
      with 100 microm laser drilled pores was used to produce oil/water emulsions
      consisting of 2 wt% Tween 20 as emulsifier, paraffin wax as dispersed oil phase
      and 0.01-0.25 wt% Carbomer (Carbopol ETD 2050) as stabilizer. The membrane tube,
      1 cm in diameter, was rotated inside a stationary glass cylinder, diameter of 3
      cm, at a constant speed in the range 50-1500 rpm. The oil phase was introduced
      inside the membrane tube and permeated through the porous wall moving radially
      into the continuous phase in the form of individual droplets. Increasing the
      membrane rotational speed increased the wall shear stress which resulted in a
      smaller average droplet diameter being produced. For a constant rotational speed,
      the average droplet diameter increased as the stabilizer content in the
      continuous phase was lowered. The optimal conditions for producing uniform
      emulsion droplets were a Carbomer content of 0.1-0.25 wt% and a membrane
      rotational speed of 350 rpm, under which the average droplet diameter was 105-107
      microm and very narrow coefficients of variation of 4.8-4.9%. A model describing
      the operation is presented and it is concluded that the methodology holds
      potential as a manufacturing protocol for both coarse and fine droplets and
      capsules.

PMID- 16563412
TI  - Micellization of CTAB in the presence of silicate anions and the exchange between
      bromide and silicate at the micelle surface: A step to understand the formation
      of mesoporous molecular sieves at extremely low surfactant and silicate
      concentrations.
AB  - The effect of silicate anions, from dilute aqueous tetramethylammonium silicate
      (TMASi) solutions (0-3.0 mmol L(-1) in silicon), on the formation of
      hexadecyltrimethylammonium bromide (CTAB) micelles was investigated by means of a
      series of simple conductivity experiments. These two compounds are used in the
      preparation of mesoporous silicate molecular sieves. An increase in the
      monovalent silicate anion concentration decreases the critical micelle
      concentration (cmc) of CTAB, as might be expected from the decreased repulsive
      forces between the polar heads of the surfactant molecules. However, the decrease
      in cmc values is less pronounced than that observed in the presence of bromide
      ions, suggesting that Br- binds more strongly than Si(OH)3O- at the micelle
      surface. Through the ion-exchange formalism, a selectivity coefficient for
      Si(OH)3O-/Br- exchange of 0.30+/-0.03 was estimated from the conductivity data.
      This value compares well with that of 0.4+/-0.1 also determined in this work by
      the pyrene fluorescence quenching method. The experimental results were used to
      rationalize the formation of a surfactant supramolecular-templated mesoporous
      molecular sieve at extremely low surfactant (0.63 mmol L(-1)) and silicate (4.00
      mmol L(-1)) concentrations.

PMID- 16563413
TI  - Surface properties of mixed monolayers of sulfobetaines and ionic surfactants.
AB  - To study the influence of the head group in the properties of the mixed
      monolayers adsorbed at the air-water interface, the surface tension and surface
      potential of binary mixtures of surfactant have been determined as a function of
      the surfactant composition. Experiments were carried out with anionic
      zwitterionic sodium dodecyl sulfate and dodecyl dimethyl ammoniopropane sulfonate
      (SDS/DDPS), and cationic-zwitterionic dodecyl trimethylammonium bromide and
      dodecyl dimethyl ammoniopropane sulfonate (DTAB/DDPS), and dodecyl
      trimethylammonium bromide and tetradecyl dimethyl ammoniopropane sulfonate
      (DTAB/TDPS). It was shown that mixed monolayers of cationic-zwitterionic
      surfactant exhibit small negative deviations of ideal behavior, whereas for
      SDS/DDPS monolayers show strong negative deviation from the ideality. Deviations
      of ideal behavior are interpreted by regular solution theory. The surface
      potential values agree very well with the concentration of the ionic component at
      the interface. The dynamic surface tension values show that the adsorption
      kinetics on the interface is a diffusion-controlled process. In monolayers with
      significant deviation of the ideal behavior, anionic-zwitterionic, there is some
      evidence of intermolecular attractions after diffusion of both surfactants at the
      interface.

PMID- 16563414
TI  - Pore structure of the packing of fine particles.
AB  - This paper presents a numerical study of the pore structure of fine particles. By
      means of granular dynamics simulation, packings of mono-sized particles ranging
      from 1 to 1000 microm are constructed. Our results show that packing density
      varies with particle size due to the effect of the cohesive van der Waals force.
      Pores and their connectivity are then analysed in terms of Delaunay tessellation.
      The geometries of the pores are represented by the size and shape of Delaunay
      cells and quantified as a function of packing density or particle size. It shows
      that the cell size decreases and the cell shape becomes more spherical with
      increasing packing density. A general correlation exists between the size and
      shape of cells: the larger the cell size relative to particle size, the more
      spherical the cell shape. This correlation, however, becomes weaker as packing
      density decreases. The connectivity between pores is represented by throat size
      and channel length. With decreasing packing density, the throat size increases
      and the channel length decreases. The pore scale information would be useful to
      understand and model the transport and mechanical properties of porous media.

PMID- 16563415
TI  - Aqueous foam films stabilized by sodium naphthenates.
AB  - Stratification of a foam liquid film drawn from aqueous solutions of sodium
      naphthenate at relatively high concentration is likely due to a lamellar liquid
      crystal-like structure within the film. Film stratification, resulting in
      stepwise thinning, has been observed in foam films formed from systems containing
      either moderate to high concentrations of surfactant or in films formed from
      solutions containing solid particles. At moderate surfactant concentrations, film
      stratification is likely due to layers of ordered spherical micelles as
      postulated in Wasan and Nikolov's model of film stratification. At high
      surfactant concentrations, stepwise thinning of the films and occurrence of
      domains of uniform color within the film suggest a lamellar liquid crystal-like
      structure within the film, potentially up to hundred or more oriented layers. The
      LLC-like structure inside the film can occur at concentrations below the lower
      limit of the LLC existence as a bulk phase.

PMID- 16563416
TI  - Production of microsized PMMA droplets using electrospraying with various
      auxiliary fields.
AB  - To fabricate uniform nano/microsized beads using the electrospraying process,
      poly(methylmethacrylate) (PMMA) polymer solution is ejected from a reservoir tip
      to form suspended droplets using the force of a controllable syringe pump. Using
      a newly designed electrode connected to the nozzle and a field-controllable
      target electrode, we obtained uniform microsized beads of the solution. Moreover,
      by using a two-axis x-y stage, we could obtain selective coverage of microsized
      PMMA droplets on an insulating PET film. To clarify the effect of the applied
      field conditions, the droplets deposited on a dielectric substrate were
      characterized under an optical microscope.

PMID- 16563417
TI  - The preparation of Pt nanoparticles by methanol and citrate.
AB  - Platinum nanoparticles of 2-3 nm average size and ca. +/-2 nm distribution can be
      successfully prepared by methanol reduction while using sodium citrate as the
      stabilizer. Sol formation was investigated by UV-visible spectroscopy and EXAFS
      (extended X-ray absorption fine structure spectroscopy). The formation of Pt
      nanoparticles was confirmed by the presence of Pt-Pt bonding in the solution
      after a certain induction period in methanol-reduced sol with or without citrate.
      The possible two-step reduction of Pt(IV) was revealed by correlating EXAFS, UV
      visible spectra and pH data. The presence of citrate resulted in a smaller Pt-Pt
      coordination number and a slower sol formation process. All these results prove
      that citrate acted as the stabilizer in this synthesis.

PMID- 16563418
TI  - Study of nickel nanoparticles supported on activated carbon prepared by aqueous
      hydrazine reduction.
AB  - Nickel nanoparticles were obtained by the reduction in hydrazine aqueous media of
      nickel acetate as a precursor supported on activated carbon of high surface area.
      Classical catalysts using nickel acetate or nitrate were prepared for comparison.
      The catalysts were characterized by N(2) physisorption, H(2)-TPR, H(2)
      adsorption, TPD, TEM, and XRD, and tested in the gas phase hydrogenation of
      benzene. Hydrazine catalysts were found much more active in benzene hydrogenation
      than corresponding classically prepared catalysts. Remarkably, their reactivity
      is comparable (turn-over frequency of 0.2001-0.2539 s(-1) at 393 K) to that of Pt
      classical catalysts supported on activated carbon in the same conditions.
      Evidence is given for the existence of the hydrogen spillover effect in benzene
      hydrogenation, not reported before in the literature. As a result of the hydrogen
      spillover effect, catalysts performances can be explained by a combination of
      surface metal atom reactivity, metal-support interaction strength, and specific
      surface area extent. Maximum effect is observed with hydrazine preparation
      method, for 1% Ni content and nickel acetate as a precursor. Unexpectedly, it was
      also found that hydrazine preparation increases the specific area of the
      catalysts.

PMID- 16563419
TI  - Troilite oxidation by hydrogen peroxide.
AB  - The kinetics and mechanism of troilite oxidation by H(2)O(2) was studied at
      temperatures of 25 and 45 degrees C. Solutions within the range 0.1-0.85 mol L(
      1) H(2)O(2) in HClO(4) (0.01-0.1 mol L(-1)) were used as dissolution media. The
      experimental amount of dissolved iron was plotted versus t(n), with n ranging
      from 0.25 to 1.55. The theoretical interpretation of this dependence suggests
      that the troilite oxidation involves several processes: Both experimental results
      and theoretical considerations illustrate the importance of temperature, pH, and
      [H(2)O(2)] for the kinetics and mechanisms of troilite oxidation. The amounts of
      dissolved iron strongly increase with temperature and [H(+)], whereas an increase
      of H(2)O(2) concentration seems to reduce the troilite oxidation. The reaction
      orders with respect to [H(+)] are variable, pointing out notable modifications of
      reaction mechanism with experimental conditions. The estimated value E(a)=25.4+/
      0.9 k J mol(-1) ([H(2)O(2)]=0.4 mol L(-1) and pH 1) points to dissolution
      kinetics controlled by a mix regime of surface reaction and diffusion.

PMID- 16563420
TI  - Adsorption of reactive dyes on titania-silica mesoporous materials.
AB  - This paper presents a study on the adsorption of two basic dyes, methylene blue
      (MB) and rhodamine B (RhB), from aqueous solution onto mesoporous silica-titania
      materials. The effect of dye structure, adsorbent particle size, TiO(2) presence,
      and temperature on adsorption was investigated. Adsorption data obtained at
      different solution temperatures (25, 35, and 45 degrees C) revealed an
      irreversible adsorption that decreased with the increment of T. The presence of
      TiO(2) augmented the adsorption capacity (q(e)). This would be due to possible
      degradation of the dye molecule in contact with the TiO(2) particles in the
      adsorbent interior. The adsorption enthalpy was relatively high, indicating that
      interaction between the sorbent and the adsorbate molecules was not only physical
      but chemical. Both Langmuir and Freundlich isotherm equations were applied to the
      experimental data. The obtained parameters and correlation coefficients showed
      that the adsorption of the two reactive dyes (MB and RhB) on the adsorbent
      systems at the three work temperatures was best predicted by the Langmuir
      isotherm, but not in all cases. The kinetic adsorption data were processed by the
      application of two simplified kinetic models, first and second order, to
      investigate the adsorption mechanism. It was found that the adsorption kinetics
      of methylene blue and rhodamine B onto the mesoporous silica-titania materials
      surface under different operating conditions was best described by the first
      order model.

PMID- 16563421
TI  - A simplified method to estimate kinetic and thermodynamic parameters on the solid
      liquid separation of pollutants.
AB  - The aim of the present study was to propose a simplified experimental-theoretical
      method for estimating the kinetic and thermodynamic parameters for the solid
      liquid separation of pollutants by using kinetic studies with batch reactors,
      i.e., the removed quantity of dissolved ion as a function of time at different
      initial concentration. This method was applied to the removal of uranyl ion
      (UO(2+)(2)) from aqueous solutions onto synthetic manganese oxide (birnessite).
      The pseudo-second-order kinetics and one-site saturation models were proposed to
      fit the experimental and calculated data, the fitting parameters being estimated
      by nonlinear regression, using the least-squares method. For initial
      concentration range 0.2-11.8 microM, the results showed that the uranyl removal
      process in dispersed batch reactors can be efficiently modeled by the proposed
      models. Then, several kinetic and thermodynamic parameters were calculated, such
      as maximal removed quantity of uranyl, q(r,max), half-removal time, t(1/2),
      initial rate of uranyl-ion removal, v(0), initial uranyl-removal coefficient, K,
      maximal rate of uranyl removal, v(0,max), mass transfer coefficient, D(transfer),
      equilibrium Langmuir constant, K(L), and constant separation factor, K(s). These
      parameters make it possible to demonstrate that the removal of U onto birnessite
      is favorable, and that the maximum surface coverage of the uranyl ions represents
      about 3% of vacant sites in the Mn layer.

PMID- 16563422
TI  - Emotional intelligence: the Sine Qua Non for a clinical leadership toolbox.
AB  - Over the past decade, it has become increasingly clear that although IQ and
      technical skills are important, emotional intelligence is the Sine Qua Non of
      leadership. According to Goleman [Goleman, D. (1998). What makes a leader?
      Harvard Business Review, 93-102] "effective leaders are alike in one crucial way:
      they all have a high degree of emotional intelligence...and can also be linked to
      strong performance." The original five dimensions of EIQ are described and
      applied to both supervisory and clinical scenarios. LEARNING OUTCOMES: As a
      result of reading this work, you will be able to: (1) define and provide an
      illustration of each of the five components of emotional intelligence (EIQ); (2)
      outline the relationship of EIQ to success in your profession and your personal
      life; (3) create a strategic action plan to enhance each dimension of EIQ in your
      daily life; (4) list at least three real-life experiences that could have
      resulted a favorable outcome with an improved EIQ; (5) complete a self-evaluation
      of your EIQ.

PMID- 16563423
TI  - The development of the memorability-based strategy: insight from a training
      study.
AB  - We investigated whether the memorability-based strategy, a process supporting the
      rejection of nonexperienced event occurrence, could be promoted through training.
      The performance of children who received memorability-based training was compared
      with that of (a) children who received source-monitoring training and (b)
      children who did not receive any specific training but were instructed to be as
      accurate as possible. Participants (142 6- to 10-year-olds) enacted common and
      bizarre actions. Eighteen days later, participants received misinformation about
      the first session. Five days after being misinformed, children were questioned
      about the first session. Compared with children in the no training condition,
      those in both training conditions reported significantly more true events, but
      only older children who received the memorability-based training were more likely
      to reject bizarre suggested events. Age interacted with action type when
      metacognitive assessments about false event rejection were examined, consistent
      with the idea that the use of the memorability-based strategy develops late
      during the elementary school years.

PMID- 16563424
TI  - An adenoviral vector for probing promoter activity in primary immune cells.
AB  - Functional analysis of the DNA regulatory regions that control gene expression
      has largely been performed through transient transfection of promoter-reporter
      constructs into transformed cells. However, transformed cells are often poor
      models of primary cells. To directly analyze DNA regulatory regions in primary
      cells, we generated a novel adenoviral luciferase reporter vector, pShuttle
      luciferase-GFP (pSLUG) that contains a promoterless luciferase cassette (with an
      upstream cloning site) for probing promoter activity, and a GFP expression
      cassette that allows for the identification of transduced cells. Recombinant
      adenoviruses generated from this vector can transduce a wide range of primary
      immune cells with high efficiency, including human macrophages, dendritic cells
      and T cells; and mouse T cells transgenic for the coxsackie and adenoviral
      receptor (CAR). In primary T cells, we show inducible nuclear factor of activated
      T cells (NF-AT) activity using a recombinant pSLUG adenovirus containing a
      consensus NF-AT promoter. We further show inducible IL-12/23 p40 promoter
      activity in primary macrophages and dendritic cells using a recombinant pSLUG
      adenovirus containing the proximal human IL-12/23 p40 promoter. The pSLUG system
      promises to be a powerful tool for the analysis of DNA regulatory regions in
      diverse types of primary immune cells.

PMID- 16563425
TI  - Quantitative measurement of nuclear translocation events using similarity
      analysis of multispectral cellular images obtained in flow.
AB  - Nuclear translocation of NF-kappaB initiates transcription of numerous genes,
      many of which are critical to host defense. Fluorescent image-based methods that
      quantify this event have historically utilized adherent cells with large
      cytoplasm-to-nuclear area ratios. However, many immunologically relevant cells
      are naturally non-adherent and have small cytoplasm-to-nuclear area ratios. Using
      the ImageStream imaging flow cytometer, we have developed a novel method that
      measures nuclear translocation in large populations using cross-correlation
      analysis of nuclear and NF-kappaB images from each cell. This approach accurately
      measures NF-kappaB translocation in cells with small cytoplasmic areas in dose-
      and time-dependent manners. Further, NF-kappaB translocation was accurately
      measured in a subset of cells contained in a mixed population and the technique
      was successfully employed to measure IRF-7 translocation in plasmacytoid
      dendritic cells (PDC) obtained from human peripheral blood. The techniques
      described here provide an objective and statistically robust method for measuring
      cytoplasmic to nuclear molecular translocation events in a variety of
      immunologically relevant cell types with characteristically low cytoplasm-to
      nuclear area ratios.

PMID- 16563426
TI  - Use of bone marrow-derived macrophages to model murine innate immune responses.
AB  - The innate immune system is composed of neutrophils and monocyte/macrophages. As
      a cell type, bone marrow-derived macrophage (BMM) are easier to study than
      neutrophils since they are still capable of cell division and have a longer life
      span. However, in comparison with neutrophils, few methodological studies on the
      production of reactive oxygen species (ROS) by such macrophages have been
      reported. Here we present studies on ROS production of this cell type under
      various conditions including the use of different priming and stimulating agents.
      In addition, we report that the de novo adhesion of BMM to tissue culture plates
      induces superoxide anion production and this can be further enhanced by
      stimulation with PMA. BMM are able to adhere to endothelial cells that have been
      activated by TNF-alpha exposure, and under these circumstances also generate ROS.
      We explored different methods to introduce gene products into BMM without
      activating them to avoid complicating subsequent studies of ROS production.
      Infection with lentiviral vectors was very efficient, allowed long-term
      expression and did not activate the BMM. We conclude that BMM are very suitable
      for the biochemical study of the oxidative burst.

PMID- 16563427
TI  - Effect of soil type on infectivity and persistence of the entomopathogenic
      nematodes Steinernema scarabaei, Steinernema glaseri, Heterorhabditis zealandica,
      and Heterorhabditis bacteriophora.
AB  - We tested the effect of soil type on the performance of the entomopathogenic
      pathogenic nematodes Steinernema scarabaei, Steinernema glaseri, Heterorhabditis
      zealandica, and Heterorhabditis bacteriophora. Soil types used were loamy sand,
      sandy loam, loam, silt loam, clay loam, acidic sand, and a highly organic potting
      mix. Infectivity was tested by exposing third-instar Anomala orientalis or
      Popillia japonica to nematodes in laboratory and greenhouse experiments and
      determining nematode establishment in the larvae and larval mortality.
      Infectivity of H. bacteriophora and H. zealandica was the highest in potting mix,
      did not differ among loamy sand and the loams, and was the lowest in acidic sand.
      Infectivity of S. glaseri was significantly lower in acidic sand than in loamy
      sand in a laboratory experiment but not in a greenhouse experiment, and did not
      differ among the other soils. Infectivity of S. scarabaei was lower in silt loam
      and clay loam than in loamy sand in a greenhouse experiment but not in a
      laboratory experiment, but was the lowest in acidic sand and potting mix.
      Persistence was determined in laboratory experiments by baiting nematode
      inoculated soil with Galleria mellonella larvae. Persistence of both
      Heterorhabditis spp. and S. glaseri was the shortest in potting mix and showed no
      clear differences among the other substrates. Persistence of S. scarabaei was
      high in all substrates and its recovery declined significantly over time only in
      clay loam. In conclusion, generalizations on nematode performance in different
      soil types have to be done carefully as the effect of soil parameters including
      soil texture, pH, and organic matter may vary with nematode species.

PMID- 16563428
TI  - Ultrastructural and molecular characterization of Haplosporidium montforti n.
      sp., parasite of the European abalone Haliotis tuberculata.
AB  - A new member of the parasitic phylum Haplosporidia, which was found infecting the
      connective tissue, gill, digestive gland, and foot muscle of Haliotis tuberculata
      imported from Ireland and experimentally grown in Galicia (NW Spain), is
      described. Scanning electron microscopy, transmission electron microscopy, and
      molecular characterization of the small subunit ribosomal RNA (SSU rRNA) gene
      were carried out to confirm the description of this species. The ultrastructural
      morphology of the spores and their surrounding ornaments attached to the spore
      wall was described from light, scanning, and transmission electron microscopy
      observations. Systemic infection with uninucleated and multinucleated plasmodia
      containing spherical nuclei was observed among several sporocysts containing the
      different spore maturation stages. The spores were spherical to slightly
      ellipsoidal (2.42 +/- 0.5 x 2.31 +/- 0.6 microm). The apical zone of the spore
      wall was modified into a complex opercular system covering a circular orifice
      that measured about 0.5 microm in diameter. The operculum was connected to the
      spore wall by a hinge. The spore wall was about 110 nm thick, with 4 filaments
      (20-28 microm long). The filaments were composed of the same material that formed
      the wall. The cross-sections through the base of these filaments showed T-like
      and X-like sections. Internally, the uninucleated endosporoplasm contained
      typical haplosporidian structures, such as, haplosporosomes, a spherulosome, and
      mitochondria with vesicular cristae. The SSU rRNA gene sequence was different
      from previously reported haplosporidian SSU rRNA gene sequences, corroborating
      morphological data that this was an undescribed species. Based on differences
      from previously described haplosporidians in ultrastructural characteristics of
      the spore and SSU rRNA gene sequence, we describe the abalone haplosporidian as
      Haplosporidium montforti n. sp.

PMID- 16563429
TI  - Male-killing Wolbachia in a live-bearing arthropod: brood abortion as a
      constraint on the spread of a selfish microbe.
AB  - Maternally inherited, cellular endosymbionts can enhance their fitness by biasing
      host sex ratio in favor of females. Male killing (MK), an extreme form of sex
      ratio manipulation, is selectively advantageous, if the death of males results in
      increased microbe transmission through female siblings. In live-bearing hosts,
      females typically produce more embryos than are brought to term, and reproductive
      compensation through maternal resource reallocation from dead male embryos to
      female siblings provides a direct, physiological mechanism that could increase
      the number of daughters born to infected females, thereby promoting MK
      endosymbiont spread. In this study, a Wolbachia-infected line and an uninfected
      line of the viviparous pseudoscorpion, Cordylochernes scorpioides were
      genetically homogenized for nuclear DNA by repeated backcrossing of the infected
      line with the uninfected, laboratory population. Photomicroscopy of early-stage
      embryos demonstrated that female C. scorpioides invariably produced an excess of
      embryos, with Wolbachia-infected females producing as many early-stage embryos as
      uninfected female controls. However, Wolbachia-infected females that successfully
      carried broods to term gave birth to significantly fewer offspring, indicating
      that the extreme female bias characteristic of their broods results from the
      killing rather than the feminization of male embryos. Infected females that
      carried broods to term gave birth to significantly larger nymphs and did produce
      10% more female offspring than uninfected females. However, the slight
      transmission advantage that the MK Wolbachia accrued from this reproductive
      compensation appears to be heavily outweighed by the high rate of spontaneous
      brood abortion suffered by infected females.

PMID- 16563431
TI  - Crystal structure of the archaeal A1Ao ATP synthase subunit B from Methanosarcina
      mazei Go1: Implications of nucleotide-binding differences in the major A1Ao
      subunits A and B.
AB  - The A1Ao ATP synthase from archaea represents a class of chimeric
      ATPases/synthases, whose function and general structural design share
      characteristics both with vacuolar V1Vo ATPases and with F1Fo ATP synthases. The
      primary sequences of the two large polypeptides A and B, from the catalytic part,
      are closely related to the eukaryotic V1Vo ATPases. The chimeric nature of the
      A1Ao ATP synthase from the archaeon Methanosarcina mazei Go1 was investigated in
      terms of nucleotide interaction. Here, we demonstrate the ability of the
      overexpressed A and B subunits to bind ADP and ATP by photoaffinity labeling.
      Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was
      used to map the peptide of subunit B involved in nucleotide interaction.
      Nucleotide affinities in both subunits were determined by fluorescence
      correlation spectroscopy, indicating a weaker binding of nucleotide analogues to
      subunit B than to A. In addition, the nucleotide-free crystal structure of
      subunit B is presented at 1.5 A resolution, providing the first view of the so
      called non-catalytic subunit of the A1Ao ATP synthase. Superposition of the A-ATP
      synthase non-catalytic B subunit and the F-ATP synthase non-catalytic alpha
      subunit provides new insights into the similarities and differences of these
      nucleotide-binding ATPase subunits in particular, and into nucleotide binding in
      general. The arrangement of subunit B within the intact A1Ao ATP synthase is
      presented.

PMID- 16563432
TI  - The autocrine motility factor (AMF) and AMF-receptor combination needs sugar
      chain recognition ability and interaction using the C-terminal region of AMF.
AB  - The autocrine motility factor (AMF) promotes cellular locomotion or invasion, and
      regulates tumor angiogenesis or ascites accumulation. These signals are triggered
      by binding between AMF and its receptor (AMFR), a glycoprotein on the cell
      surface. AMF has been identified as phosphohexose isomerase (PHI). Previous
      reports have suggested that the substrate-recognition of exo-PHI is significant
      for receptor binding. Crystallographic studies have shown that AMF consists of
      three domains, and that the substrate or inhibitor of PHI is stored between the
      large and small domains, corresponding to approximately residues 117-288. Here,
      site-directed mutagenesis was used to investigate 18 recombinant human AMF point
      mutants involving critical amino acid residues for substrate or enzyme inhibitor
      recognition or binding. Mutation of residues that interact with the phosphate
      group of the PHI substrate significantly reduced the cell motility-stimulating
      activity. Their binding capacities for AMFR were also lower than wild-type human
      AMF. Mutants that retained the enzymic activity showed the motility-stimulating
      effect and receptor binding and had sensitivity to a PHI inhibitor. Mutant AMFR
      lacking the N-sugar chain was expressed on the cell membrane but did not respond
      to AMF-stimulation, and N-glycosidase-treated AMFR did not compete with receptor
      binding of AMF. Furthermore, the AMF domains that contain the substrate storage
      domain and C-terminal region stimulate cell locomotion. These results suggest
      that the N-glyco side-chain of AMFR is a trigger and that interaction between the
      117-C-terminal part of AMF and the extracellular core protein of AMFR is needed
      during AMF-AMFR interactions.

PMID- 16563430
TI  - Isolation of human antibody repertoires with preservation of the natural heavy
      and light chain pairing.
AB  - The humoral immune system in higher vertebrates is unique in its ability to
      generate highly diverse antibody responses against most pathogens as well as
      against certain malignancies. Several technologies have been developed to exploit
      this vast source of potentially therapeutic antibodies, including hybridoma
      technology, phage display and yeast display. Here, we present a novel, high
      throughput technology (the Symplex Technology) for rapid direct cloning and
      identification of human antigen-specific high-affinity antibodies from single
      antibody-producing cells of immune individuals. The utility of the technology was
      demonstrated by isolation of diverse sets of unique high-affinity antibodies
      against tetanus toxoid and influenza virus from immunized volunteers. Hence, the
      Symplex Technology is a new method for the rapid isolation of high-affinity
      antibodies directly from humans.

PMID- 16563434
TI  - Structural basis for monoubiquitin recognition by the Ede1 UBA domain.
AB  - Monoubiquitination is a general mechanism for downregulating the activity of cell
      surface receptors by consigning these proteins for lysosome-mediated degradation
      through the endocytic pathway. The yeast Ede1 protein functions at the
      internalization step of endocytosis and binds monoubiquitinated proteins through
      a ubiquitin associated (UBA) domain. UBA domains are found in a broad range of
      cellular proteins but previous studies have suggested that the mode of ubiquitin
      recognition might not be universally conserved. Here we present the solution
      structure of the Ede1 UBA domain in complex with monoubiquitin. The Ede1 UBA
      domain forms a three-helix bundle structure and binds ubiquitin through a largely
      hydrophobic surface in a manner reminiscent of the Dsk2 UBA and the remotely
      homologous Cue2 CUE domains, for which high-resolution structures have been
      described. However, the interaction is dissimilar to the molecular models
      proposed for the hHR23A UBA domains bound to either monoubiquitin or Lys48-linked
      diubiquitin. Our mutational analyses of the Ede1 UBA domain-ubiquitin interaction
      reveal several key affinity determinants and, unexpectedly, a negative affinity
      determinant in the wild-type Ede1 protein, implying that high-affinity
      interactions may not be the sole criterion for optimal function of monoubiquitin
      binding endocytic proteins.

PMID- 16563433
TI  - Filling small, empty protein cavities: structural and energetic consequences.
AB  - Most proteins contain small cavities that can be filled by replacing cavity
      lining residues by larger ones. Since shortening mutations in hydrophobic cores
      tend to destabilize proteins, it is expected that cavity-filling mutations may
      conversely increase protein stability. We have filled three small cavities in
      apoflavodoxin and determined by NMR and equilibrium unfolding analysis their
      impact in protein structure and stability. The smallest cavity (14 A3) has been
      filled, at two different positions, with a variety of residues and, in all cases,
      the mutant proteins are locally unfolded, their structure and energetics
      resembling those of an equilibrium intermediate of the thermal unfolding of the
      wild-type protein. In contrast, two slightly larger cavities of 20 A3 and 21 A3
      have been filled with Val to Ile or Val to Leu mutations and the mutants preserve
      both the native fold and the equilibrium unfolding mechanism. From the known
      relationship, observed in shortening mutations, between stability changes and the
      differential hydrophobicity of the exchanged residues and the volume of the
      cavities, the filling of these apoflavodoxin cavities is expected to stabilize
      the protein by approximately 1.5 kcal mol(-1). However, both urea and thermal
      denaturation analysis reveal much more modest stabilizations, ranging from 0.0
      kcal mol(-1) to 0.6 kcal mol(-1), which reflects that the accommodation of single
      extra methyl groups in small cavities requires some rearrangement, necessarily
      destabilizing, that lowers the expected theoretical stabilization. As the size of
      these cavities is representative of that of the typical small, empty cavities
      found in most proteins, it seems unlikely that filling this type of cavities will
      give rise to large stabilizations.

PMID- 16563435
TI  - Alternate pathways for folding in the flavodoxin fold family revealed by a
      nucleation-growth model.
AB  - A recent study of experimental results for flavodoxin-like folds suggests that
      proteins from this family may exhibit a similar, signature pattern of folding
      intermediates. We study the folding landscapes of three proteins from the
      flavodoxin family (CheY, apoflavodoxin, and cutinase) using a simple nucleation
      and growth model that accurately describes both experimental and simulation
      results for the transition state structure, and the structure of on-pathway and
      misfolded intermediates for CheY. Although the landscape features of these
      proteins agree in basic ways with the results of the study, the simulations
      exhibit a range of folding behaviours consistent with two alternate folding
      routes corresponding to nucleation and growth from either side of the central
      beta-strand.

PMID- 16563436
TI  - The Arabidopsis genome encodes structurally and functionally diverse HMGB-type
      proteins.
AB  - The high mobility group (HMG) proteins of the HMGB family are chromatin
      associated proteins that act as architectural factors in nucleoprotein
      structures, which regulate DNA-dependent processes including transcription and
      recombination. In addition to the previously identified HMGB1-HMGB6 proteins, the
      Arabidopsis genome encodes at least two other candidate family members (encoded
      by the loci At2g34450 and At5g23405) having the typical overall structure of a
      central domain displaying sequence similarity to HMG-box DNA binding domains,
      which is flanked by basic N-terminal and acidic C-terminal regions. Subcellular
      localisation experiments demonstrate that the At2g34450 protein is a nuclear
      protein, whereas the At5g23405 protein is found mainly in the cytoplasm. In line
      with this finding, At5g23405 displays specific interaction with the nuclear
      export receptor AtXPO1a. According to CD measurements, the HMG-box domains of
      both proteins have an alpha-helical structure. The HMG-box domain of At2g34450
      interacts with linear DNA and binds structure-specifically to DNA minicircles,
      whereas the HMG-box domain of At5g23405 does not interact with DNA at all. In
      ligation experiments with short DNA fragments, the At2g34450 HMG-box domain can
      facilitate the formation of linear oligomers, but it does not promote the
      formation of DNA minicircles. Therefore, the At2g34450 protein shares several
      features with HMGB proteins, whereas the At5g23405 protein has different
      characteristics. Despite the presence of a region with similarity to the
      nucleosome-binding domain typical of HMGN proteins, At2g34450 does not bind
      nucleosome particles. In summary, our data demonstrate (i) that plant HMGB-type
      proteins are functionally variable and (ii) that it is difficult to predict HMG
      box function solely based on sequence similarity.

PMID- 16563437
TI  - Subclinical psychopathology and socio-economic status in unaffected twins
      discordant for affective disorder.
AB  - BACKGROUND: The most potent risk factor for affective disorders is a family
      history of affective disorder but the specific factors that are transmitted in
      families are unknown. It is possible to investigate the relation between risk
      factors and affective disorder by using a high-risk design e.g.: a study of the
      healthy relatives of patients with affective disorders. AIM: To compare
      psychopathology and socio-economic status between twins with a co-twin history of
      affective disorder and twins without. METHODS: In a cross-sectional high-risk
      case-control study, healthy monozygotic and dizygotic twins with (High-Risk
      twins) and without (Low-Risk twins) a co-twin history of affective disorder were
      identified through nation-wide registers. Participants were assessed using semi
      structured psychiatric interviews and self-rating of psychopathology. RESULTS:
      High-Risk twins had a lower education level, a lower work position and tendency
      towards being more often unemployed and early retired than the Low-Risk twins.
      Furthermore, they presented higher rates of subclinical affective symptoms and
      were more likely to experience a minor psychiatric diagnosis. CONCLUSION: Healthy
      twins with a high genetic liability to affective disorder seem to present lower
      socio-economic status, higher rates of subclinical affective symptoms and more
      often experience a minor psychiatric diagnosis than twins with no familial
      history of affective disorder. It is not possible from the present cross
      sectional data to determine the causality of these findings, thus genetic
      liability to affective disorder, socio-economic status and minor psychopathology
      seem to have a complex interrelation.

PMID- 16563438
TI  - Inositol hexaphosphate (IP6) inhibits cellular proliferation in melanoma.
AB  - BACKGROUND: Inositol Hexaphosphate (IP6) is a naturally occurring
      polyphosphorylated carbohydrate found in food sources high in fiber content. We
      have previously reported IP6 to have significant inhibitory effects against
      pancreatic cancer in vitro. We hypothesized that the IP6 would significantly
      inhibit cell growth of cutaneous melanoma in vitro. MATERIALS AND METHODS: The
      melanoma line HTB68 was cultured using standard techniques and treated with IP6
      at doses ranging from 0.2 to 1.0 mM/well. Cell viability was measured by MTT at
      72 h. VEGF production was measured in the cell supernatants by ELISA. Apoptosis
      was evaluated by Annexin V-FITC and results calculated using FACS analysis.
      Statistical analysis was performed by ANOVA. RESULTS: Significant reductions (P <
      0.001) in cellular proliferation were observed with IP6. Overall, IP6 exhibited a
      mean inhibition of cell growth of 52.1 +/- 11.5% (range, 1.6-83.0%) at 72 h of
      incubation. VEGF production was significantly reduced (P < 0.001) by the addition
      of IP6 (7.5 pg/ml) compared to control (40.9 pg/ml). IP6 significantly increased
      (P = 0.029) late apoptosis from 5.3 to 7.0% gated events. No changes in necrosis
      or early apoptosis were observed. CONCLUSIONS: Adjuvant treatment of melanoma
      continues to challenge clinicians and patients. Our findings that IP6
      significantly decreased cellular growth, VEGF production and increased late
      apoptosis in melanoma suggest its potential therapeutic value. Further in vivo
      studies are planned to evaluate safety and clinical utility of this agent.

PMID- 16563439
TI  - Rotational vertigo associated with parietal cortical infarction.
AB  - A 65-year-old woman experienced sudden positional vertigo with rightward,
      horizontal nystagmus that resolved within days. MRI revealed a left parietal lobe
      infarction involving the supramarginal gyrus. The patient experienced a transient
      recurrence of vertigo after 7 days but MRI failed to reveal the presence of any
      new lesions; furthermore, the patient's EEG was normal. We suggest that this
      patient's vertigo was due to her parietal cortical infarction.

PMID- 16563440
TI  - Hodgkin-Huxley type ion channel characterization: an improved method of voltage
      clamp experiment parameter estimation.
AB  - The Hodgkin-Huxley formalism for quantitative characterization of ionic channels
      is widely used in cellular electrophysiological models. Model parameters for
      these individual channels are determined from voltage clamp experiments and
      usually involve the assumption that inactivation process occurs on a time scale
      which is infinitely slow compared to the activation process. This work shows that
      such an assumption may lead to appreciable errors under certain physiological
      conditions and proposes a new numerical approach to interpret voltage clamp
      experiment results. In simulated experimental protocols the new method was shown
      to exhibit superior accuracy compared to the traditional least squares fitting
      methods. With noiseless input data the error in gating variables and time
      constants was less than 1%, whereas the traditional methods generated upwards of
      10% error and predicted incorrect gating kinetics. A sensitivity analysis showed
      that the new method could tolerate up to approximately 15% perturbation in the
      input data without unstably amplifying error in the solution. This method could
      also assist in designing more efficient experimental protocols, since all channel
      parameters (gating variables, time constants and maximum conductance) could be
      determined from a single voltage step.

PMID- 16563441
TI  - Lycium barbarum polysaccharides: Protective effects against heat-induced damage
      of rat testes and H2O2-induced DNA damage in mouse testicular cells and
      beneficial effect on sexual behavior and reproductive function of hemicastrated
      rats.
AB  - Lycium barbarum, a famous Chinese medicinal herb, has a long history of use as a
      traditional remedy for male infertility. Polysaccharides are the most important
      functional constituent in L. barbarum fruits. We systematically investigated the
      effect of L. barbarum polysaccharides (LBP) on rat testis damage induced by a
      physical factor (43 degrees C heat exposure), on DNA damage of mouse testicular
      cells induced by a chemical factor (H2O2), and on sexual behavior and
      reproductive function of hemicastrated male rats. The results showed that LBP
      provided a protective effect against the testicular tissue damage induced by heat
      exposure. When compared with negative control, a suitable concentration of LBP
      significantly increased testis and epididymis weights, improved superoxide
      dismutase (SOD) activity, and raised sexual hormone levels in the damaged rat
      testes. LBP had a dose-dependent protective effect against DNA oxidative damage
      of mouse testicular cells induced by H2O2. LBP improved the copulatory
      performance and reproductive function of hemicastrated male rats, such as
      shortened penis erection latency and mount latency, regulated secretion of sexual
      hormones and increased hormone levels, raised accessory sexual organ weights, and
      improved sperm quantity and quality. The present findings support the folk
      reputation of L. barbarum fruits as an aphrodisiac and fertility-facilitating
      agent, and provide scientific evidence for a basis for the extensive use of L.
      barbarum fruits as a traditional remedy for male infertility in China.

PMID- 16563442
TI  - Reversal of methamphetamine-induced behavioral sensitization by repeated
      administration of a dopamine D1 receptor agonist.
AB  - Repeated intermittent administration of methamphetamine (MAP) produces an
      enduring hypersensitivity to the motor stimulant effect of MAP, termed behavioral
      sensitization. Dopamine plays a critical role in the development and expression
      of behavioral sensitization. Here, we investigated whether a dopamine D1 receptor
      agonist could reverse behavioral sensitization to MAP. Administration of MAP (1.0
      mg/kg, i.p.) to rats once every 3 days for a total of 5 times (days 1-13) induced
      the enhancement of locomotor activity after MAP challenge (0.5 mg/kg, i.p.) on
      day 20, verifying the development of behavioral sensitization. The MAP-sensitized
      rats then received a dopamine D1 agonist, R-(+)-SKF38393 (3.0 mg/kg, i.p.), once
      a day for 7 consecutive days (days 21-27). Behavioral analysis on days 30 and 41
      revealed that the enhanced locomotor activity was reversed by repeated R-(+)
      SKF38393 administration. Moreover, repeated R-(+)-SKF38393 administration
      reversed the increased dopamine release in the striatum after MAP challenge on
      day 41. Thus, repeated administration of the dopamine D1 receptor agonist induces
      the reversal of established behavioral sensitization to MAP and of increased
      dopamine release in the striatum, lasting for at least 2 weeks. Dopamine D1
      receptor agonists may be useful therapeutic agents for the treatment of
      psychostimulant addiction.

PMID- 16563444
TI  - The animal model in food intake regulation: examples from the opioid literature.
AB  - Animal models allow us to investigate the basic mechanisms by which food intake
      is regulated. There are a host of neuroregulators distributed across a complex
      central network that control eating behavior. The opioid peptides represent one
      family of such regulators that have been studied extensively in animals. Using
      anatomical, biochemical and behavioral methods investigators have found that
      opioids play an important role in reward-related eating. In this brief review we
      summarize representative animal studies that utilize a variety of experimental
      techniques to help explain the role of opioids in ingestive behavior.

PMID- 16563443
TI  - mGlu1 and mGlu5 receptor antagonists lack anticonvulsant efficacy in rodent
      models of difficult-to-treat partial epilepsy.
AB  - Modulation of metabotropic glutamate (mGlu) receptors represents an interesting
      new approach for the treatment of a range of neurological and psychiatric
      disorders. Several lines of evidence suggest that functional blockade of group I
      (mGlu1 and mGlu5) receptors may be beneficial for treatment of epileptic
      seizures. This study was conducted to investigate whether mGlu1 or mGlu5 receptor
      antagonists have the potential to block partial or secondarily generalized
      seizures as occurring in partial epilepsy, the most common and difficult-to-treat
      type of epilepsy in patients. For this purpose, we systemically administered
      novel highly selective and brain penetrable group I mGlu receptor antagonists,
      i.e., the mGlu1 receptor antagonist EMQMCM [3-ethyl-2-methyl-quinolin-6-yl-(4
      methoxy-cyclohexyl)-methanone methanesulfonate] and the mGlu5 receptor antagonist
      MTEP ([(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine), at doses appropriate for
      mGlu1 or mGlu5 receptor-mediated effects in rodent models of partial seizures.
      Two models were used: the 6-Hz electroshock model of partial seizures in mice and
      the amygdala-kindling model in rats. Clinically established antiepileptic drugs
      were included in the experiments for comparison. Antiepileptic drugs exerted
      significant anticonvulsant effects in both models, while EMQMCM and MTEP were
      ineffective in this regard, although both compounds were administered up to doses
      associated with essentially full receptor occupancy and with typical mGlu
      receptor-mediated effects in rodent models of anxiety or pain. Brain
      microdialysis for determining extracellular levels of MTEP following i.p.
      administration in rats substantiated that effective brain concentrations were
      reached at times of our experiments in seizure models. The present results do not
      support a significant anticonvulsant potential of group I mGlu receptor
      antagonists in rodent models of difficult-to-treat partial epilepsy.

PMID- 16563445
TI  - Aryltetralol and aryltetralone lignans from Holostylis reniformis.
AB  - Aryltetralol and aryltetralone lignans were isolated from the hexane extracts of
      the roots of Holostylis reniformis. Their structures were determined by
      spectroscopic methods and chemical transformations.

PMID- 16563446
TI  - HPLC analysis of geometrical isomers of lutein epoxide isolated from dandelion
      (Taraxacum officinale F. Weber ex Wiggers).
AB  - Lutein epoxide has been isolated from petals of dandelion (Taraxacum officinale
      F. Weber ex Wiggers) by thin-layer chromatography (TLC) on silica to be used for
      the accurate identification of this carotenoid in other sources. The extract was
      analyzed by high-performance liquid chromatography (HPLC) using a C(30) column,
      as a result of which six geometrical isomers were separated. The identification
      of these isomers was performed on the basis of their UV/vis spectroscopic
      features in the mobile phase. In quantitative terms, it was observed that all-E
      lutein epoxide was the major carotenoid and that there were also high amounts of
      the (9Z)- and (9'Z)-isomers, although the latter may be an artifact.

PMID- 16563447
TI  - Functional characterization of CmCCD1, a carotenoid cleavage dioxygenase from
      melon.
AB  - Carotenoids are nutritionally important tetraterpenoid pigments that upon
      oxidative cleavage give rise to apocarotenoid (norisoprene) aroma volatiles. beta
      Carotene is the predominant pigment in orange-fleshed melon (Cucumis melo L.)
      varieties, reaching levels of up to 50 microg/gFW. Pale green and white cultivars
      have much lower levels (0-10 microg/gFW). In parallel, beta-ionone, the 9,10
      cleavage product of beta-carotene, is present (12-33ng/gFW) in orange-fleshed
      melon varieties that accumulate beta-carotene, and in much lower levels (0-5
      ng/gFW) in pale green and white fleshed varieties. A search for a gene putatively
      responsible for the cleavage of beta-carotene into beta-ionone was carried out in
      annotated melon fruit EST databases yielding a sequence (CmCCD1) highly similar
      (84%) to other plant carotenoid cleavage dioxygenase genes. To test its function,
      the clone was overexpressed in Escherichia coli strains previously engineered to
      produce different carotenoids. We show here that the CmCCD1 gene product cleaves
      carotenoids at positions 9,10 and 9',10', generating geranylacetone from
      phytoene; pseudoionone from lycopene; beta-ionone from beta-carotene, as well as
      alpha-ionone and pseudoionone from delta-carotene. CmCCD1 gene expression is
      upregulated upon fruit development both in orange, pale-green and white melon
      varieties, despite the lack of apocarotenoid volatiles in the later. Thus, the
      accumulation of beta-ionone in melon fruit is probably limited by the
      availability of carotenoid substrate.

PMID- 16563448
TI  - Pyranocoumarins from the twigs of Mammea siamensis.
AB  - Four unusual pyranocoumarins (1-4) have been isolated from the dried twigs of M.
      siamensis. The structures were determined by spectroscopic data, especially 1D
      and 2D NMR experiments.

PMID- 16563449
TI  - Synthesis of 7alpha-substituted derivatives of 17beta-estradiol.
AB  - Estrogen receptor (ER) pure antagonists such as ICI-182,780 (fulvestrant) are
      effective alternatives to tamoxifen (an ER antagonist/weak partial agonist) in
      the treatment of postmenopausal, receptor-positive human breast cancers.
      Structurally, these pure antagonists contain the basic core structure of 17beta
      estradiol (E(2)) with a long side chain attached to its C-7alpha position. We
      explored and compared in this study various synthetic routes for preparing a
      number of C-7alpha-substituted derivatives of E(2), which are highly useful for
      the design and synthesis of high-affinity ER antagonists, ER-based imaging
      ligands, and other ER-based multi-functional agents. Using E(2) as the starting
      material and 1-iodo-6-benzyloxyhexane as a precursor for the C-7alpha side chain,
      a seven-step synthetic procedure afforded 3,17beta-bis(acetoxy)-7alpha-(6
      hydroxyhexanyl)-estra-1,3,5(10)-triene (one of the derivatives prepared) in an
      overall yield of approximately 45% as compared to other known procedures that
      afforded substantially lower overall yield (8-27%). The synthetic steps for this
      representative compound include: (1) protection of the C-3 and C-17beta hydroxyls
      of E(2) using methoxymethyl groups; (2) hydroxylation of the C-6 position of the
      bismethoxymethyl ether of E(2); (3) Swern oxidation of the C-6 hydroxy to the
      ketone group; (4) C-7alpha alkylation of the C-6 ketone derivative of E(2); (5)
      deprotection of the two methoxymethyl groups; (6) reprotection of the C-3 and C-6
      free hydroxyls with acetyl groups; (7) removal of the C-6 ketone and the benzyl
      group on the side chain by catalytic hydrogenation in acetic acid. As predicted,
      two of the representative C-7alpha-substituted derivatives of E(2) synthesized in
      the present study retained strong binding affinities (close to those of E(2) and
      ICI-182,780) for the human ERalpha and ERbeta subtypes as determined using the
      radioligand-receptor binding assays.

PMID- 16563450
TI  - The stationary distribution of allele frequencies when selection acts at unlinked
      loci.
AB  - We consider population genetics models where selection acts at a set of unlinked
      loci. It is known that if the fitness of an individual is multiplicative across
      loci, then these loci are independent. We consider general selection models, but
      assume parent-independent mutation at each locus. For such a model, the joint
      stationary distribution of allele frequencies is proportional to the stationary
      distribution under neutrality multiplied by a known function of the mean fitness
      of the population. We further show how knowledge of this stationary distribution
      enables direct simulation of the genealogy of a sample at a single-locus. For a
      specific selection model appropriate for complex disease genes, we use simulation
      to determine what features of the genealogy differ between our general selection
      model and a multiplicative model.

PMID- 16563451
TI  - Anticancer activity of litchi fruit pericarp extract against human breast cancer
      in vitro and in vivo.
AB  - Litchi fruit pericarp (LFP) extract contains significant amounts of polyphenolic
      compounds and exhibits powerful antioxidative activity against fat oxidation in
      vitro. The purpose of this study is to confirm the anticancer activity of LFP
      extract on human breast cancer in vitro and in vivo, and to elucidate the
      mechanism of its activity. Human breast cancer cells were tested in vitro for
      cytotoxicity, colony formation inhibition, BrdU incorporation, and gene
      expression profiling after treatment with LFP extract. Seven nude mice bearing
      human breast infiltrating duct carcinoma orthotopically were tested for its
      anticancer activity and expression of caspase-3 in vivo by oral administration of
      0.3% (0.3 mg/ml) of LFP water-soluble crude ethanolic extract (CEE) for 10 weeks.
      LFP extract demonstrated a dose- and time-dependent inhibitory effect on cell
      growth (IC(50) = 80 microg/ml), and it significantly inhibited colony formation
      and BrdU incorporation of human breast cancer cells. Oligonucleotide microarray
      analysis identified 41(1.22%) up-regulated and 129 (3.84%) down-regulated genes
      after LFP water-soluble CEE treatment; the predominantly up-regulated genes were
      involved in various biological functions including cell cycle regulation and cell
      proliferation, apoptosis, signal transduction and transcriptional regulation, and
      extracellular matrix/adhesion molecules; and down-regulated genes were mainly
      associated with adhesion, invasion, and malignancy of cancer cells. A 40.70%
      tumor mass volume reduction and significant increase of casepase-3 protein
      expression were observed in vivo experiment. The findings in this study suggested
      that LFP extract might have potential anticancer activity on both ER positive and
      negative breast cancers, which could be attributed, in part, to its DNA damage
      effect, proliferating inhibition and apoptosis induction of cancer cells through
      up-regulation and down-regulation of multiple genes involved in cell cycle
      regulation and cell proliferation, apoptosis, signal transduction and
      transcriptional regulation, motility and invasiveness of cancer cells; ADP
      ribosyltransferase (NAD+; poly (ADP-ribose) polymerase)-like 1 (ADPRTL1),
      Cytochrome P450, subfamily I (CYP1A1) and Hyaluronan-mediated motility receptor
      (HMMR) might be the main molecular targets at which LFP water-soluble CEE acted.

PMID- 16563452
TI  - The protective effect of hydrated sodium calcium aluminosilicate against
      haematological, biochemical and pathological changes induced by Zearalenone in
      mice.
AB  - Hydrated sodium calcium aluminosilicate (HSCAS), an anticaking agent for mixed
      feed, was added alone or simultaneously with a toxic Zearalenone (ZEN) dose to
      balb/c mice and was evaluated for its ability to restore damages induced by ZEN.
      The latter is a mycotoxin produced by fusarium genera; it is mainly known to
      induce several toxic effects such as hepatotoxicity, immunotoxicity and
      nephrotoxicity on animals and humans. The experimental approach consisted of
      eight treatments of six mice each by 400 mg/kg bw or 5 g/kg bw of HSCAS. Two
      experimental groups have received respectively ZEN alone at 40 (8% of LD50) and
      at 500 mg/kg bw (LD50). Two other groups have received ZEN at 40 or 500 mg/kg bw
      combined respectively with HSCAS at 400 mg/kg bw and 5 g/kg bw. The control
      groups received water or olive oil. Forty-eight hours after treatment, blood
      samples were collected for haematological and serum biochemical parameters
      measurements. ZEN treatment significantly increased hematocrit, haemoglobin,
      white blood cells: lymphocytes, eosinophils, neutrophils, monocytes and the most
      of biochemical serum parameters; it significantly reduced platelets and induced
      degenerative changes in the hepatic and renal tissues; while, the mixture of
      HSCAS with ZEN induced a reestablishment of haematological parameters, levels of
      serum biochemical enzyme activities and histological pictures of both liver and
      kidney. It also prevented general toxicity of ZEN. This was observed by the shift
      of LD50 for this toxin. Thus, our data strongly suggested that deleterious
      effects of ZEN could be overcome or, at least, significantly were diminished by
      HSCAS. Moreover, this sorbent by itself did not show any toxic effects.

PMID- 16563453
TI  - New demodulation filter in digital phase rotation beamforming.
AB  - In this paper, we present a new quadrature demodulation filter to reduce hardware
      complexity in digital phase rotation beamforming. Due to its low sensitivity to
      phase delay errors, digital quadrature demodulation is commonly used in
      ultrasound machines. However, since it requires two lowpass filters for each
      channel to remove harmonics, the direct use of conventional finite impulse
      response (FIR) filters in ultrasound machines is computationally expensive and
      burdensome. In our new method, an efficient multi-stage uniform coefficient
      (MSUC) filter is utilized to remove harmonic components in phase rotation
      beamforming. In comparison with the directly implemented FIR (DI-FIR) and the
      previously-proposed signed-power-of-two FIR (SPOT-FIR) lowpass filters, the
      proposed MSUC filter reduces the necessary hardware resources by 93.9% and 83.9%,
      respectively. In simulation, the MSUC filter shows a negligible degradation in
      image quality. The proposed method resulted in comparable spatial and contrast
      resolution to the DI-FIR approach in the phantom study. These preliminary results
      indicate that the proposed quadrature demodulation filtering method could
      significantly reduce the hardware complexity in phase rotation beamforming while
      maintaining comparable image quality.

PMID- 16563454
TI  - Chimeric HIV-1 containing SIV matrix exhibit enhanced assembly in murine cells
      and replicate in a cell-type-dependent manner in human T cells.
AB  - Murine fibroblasts expressing viral receptors and human cyclin T1 allow HIV-1
      entry and viral gene expression but do not support efficient assembly. A chimeric
      HIV-1 carrying a non-homologous matrix (MA) from murine leukemia virus in place
      of HIV-1 MA can assemble efficiently in murine cells, yet has poor infectivity.
      Here, we assess the ability of a homologous MA from SIV MAC239 to complement
      assembly and infection in chimeric viruses designated SHIV(MA). The resulting
      SHIV(MA) chimeras produce more virus than native HIV-1 when transfected into
      murine cells. SHIV(MA) exhibits cell-type-specific replication in human T cell
      lines, replicating well in MT4 cells and poorly in Jurkat cells due to an
      incompatibility with the HIV-1 Env. The infectivity defects of SHIV(MA) are
      rescued by pseudotyping with VSV-G but not by truncation of the cytoplasmic tail
      of Env. Passage of SHIV(MA) in Jurkat cells produces variants with improved Env
      incorporation and improved replication in Jurkat but not in 3T3 TXC cells. The
      results indicate that cell-type-specific, or species-specific, host factors
      interact with MA to modulate the efficiency of assembly and its compatibility
      with Env. With additional selection, SIV/HIV-1 chimeras may be useful for the
      development of murine models of lentiviral infection.

PMID- 16563455
TI  - Respiratory dysfunction and proinflammatory chemokines in the pneumonia virus of
      mice (PVM) model of viral bronchiolitis.
AB  - We explore relationships linking clinical symptoms, respiratory dysfunction, and
      local production of proinflammatory chemokines in the pneumonia virus of mice
      (PVM) model of viral bronchiolitis. With a reduced inoculum of this natural
      rodent pathogen, we observe virus clearance by day 9, while clinical symptoms and
      respiratory dysfunction persist through days 14 and 17 postinoculation,
      respectively. Via microarray and ELISA, we identify expression profiles of
      proinflammatory mediators MIP-1alpha, MCP-1, and MIP-2 that correlate with
      persistent respiratory dysfunction. MIP-1alpha is localized in bronchial
      epithelium, which is also the major site of PVM replication. Interferon-gamma was
      detected in lung tissue, but at levels that do not correlate with respiratory
      dysfunction. Taken together, we present a modification of our pneumovirus
      infection model that results in improved survival and data that stand in support
      of a connection between local production of specific mediators and persistent
      respiratory dysfunction in the setting of acute viral bronchiolitis.

PMID- 16563456
TI  - Augmenting the immunogenicity of DNA vaccines: role of plasmid-encoded Flt-3
      ligand, as a molecular adjuvant in genetic vaccination.
AB  - In this study, we have taken advantage of the unique property of a potent
      dendritic cell (DC) growth factor, Flt-3 ligand (FL), which could act as a
      vaccine adjuvant. Accordingly, a single injection of plasmid DNA coding for
      soluble FL (FLex) was shown to induce large numbers of DCs in various tissue
      compartments and was critical for generating high frequencies of antigen-specific
      (HIV gp120 and LCMV NP) immune responses in mice. Interestingly, this enhanced
      level of immune response is strictly dependent on the co-delivery (i.m.) of the
      DNA vaccines and hFLex DNA to mice harboring large numbers of DCs. The high
      frequencies of antigen-specific CD8(+) T cells were largely associated with the
      expansion phase of DCs in vivo. However, DC expansion and immune enhancement have
      not reciprocally maintained a linear correlation, suggesting that other factors,
      cytokines/chemokines, which have the potential to modulate the microenvironment
      of DCs, could influence immunological outcome in this vaccination modality.

PMID- 16563457
TI  - Suppression of mRNA accumulation by the duck hepatitis B virus reverse
      transcriptase.
AB  - Hepadnaviruses establish chronic liver infections, but the mechanisms of
      persistence and immune evasion are poorly understood. We previously found that
      the duck hepatitis B virus (DHBV) and hepatitis B virus reverse transcriptases (P
      protein) unexpectedly accumulate in the cytoplasm where they could affect
      function(s) beyond viral DNA synthesis, such as gene expression. Therefore, we
      measured effects of DHBV P on gene expression from reporter constructs and the
      viral genome. P reduced reporter expression at the mRNA level to approximately 30
      40%, independent of reporter tested. Accumulation of the viral pregenomic RNA
      from its native promoter was suppressed three-to four-fold by P, and accumulation
      of the capsid protein and intracellular core particles was similarly suppressed
      because the pregenomic RNA encodes the capsid protein. Therefore, suppression of
      the pregenomic RNA by DHBV P creates a negative feedback loop to limit viral
      antigen accumulation and replication, possibly contributing to maintenance of
      chronic infection.

PMID- 16563458
TI  - Isolation of human immunodeficiency virus-type 1 (HIV-1) clones with biological
      and molecular properties of the primary isolate.
AB  - We developed a new biological cloning system for HIV-1 isolates using the U87.CD4
      cell lines that express different chemokine receptors. We demonstrate that our
      method is sensitive and specific because the clones isolated had the same
      coreceptor usage and genotype as viruses of the primary isolate. We evaluated our
      cloning system by isolating 27 biological clones from two primary HIV-1 R3R5X4
      isolates. Three HIV-1 phenotypes (R3R5X4, R3R5 and R5) were identified in isolate
      29 and two (R3R5X4 or R5X4) in isolate 31. Each phenotype was distinguished by a
      unique genotype. Sequencing of 20 molecular clones from each isolate did not
      reveal additional genotypes. One of the three genotypes identified from isolate
      29 was not found by molecular cloning of the original isolate, suggesting high
      specificity and sensitivity of the biological cloning system in isolating minor
      virus populations. Our results suggest that the new cloning approach can be used
      as an alternative to the existing method for isolating biological clones in PBMC.

PMID- 16563459
TI  - Meta- and paracontrast reveal differences between contour- and brightness
      processing mechanisms.
AB  - We investigated meta- and paracontrast masking using tasks requiring observers to
      judge the surface brightness or else the contours of target stimuli. The contour
      task revealed strongest metacontrast at SOAs shorter than those obtained for the
      brightness task. Paracontrast revealed related temporal differences between the
      tasks. Additionally, the paracontrast results support the existence not only of
      prolonged inhibitory effects but also of facilitatory effects. The combined
      results comport with the existence of cortical mechanisms for: (i) fast contour
      processing, (ii) slow surface-brightness processing, (iii) prolonged inhibition,
      and (iv) facilitation.

PMID- 16563460
TI  - Biases in judgments of separation and orientation of elements belonging to
      different clusters.
AB  - If two demarcated dots are embedded in separate clusters of similar dots in off
      centre positions, their perceived separation is biased towards the separation
      between the centres of the clusters (Morgan, Hole, & Glennerster, 1990). We
      replicated these results and went on to determine whether a similar bias is
      present for orientation judgments, using a staircase method and a range of
      cluster orientations and separations. A complex pattern of biases was found
      including biases for targets at centroids. Orientation attraction towards
      tangents to the clusters seemed to be involved. We conclude that orientation is
      subject to different contextual constraints from separation, and that bias
      towards the edges of clusters needs to be included in models of position coding.

PMID- 16563461
TI  - Sorption of acetaminophen, 17alpha-ethynyl estradiol, nalidixic acid, and
      norfloxacin to silica, alumina. and a hydrophobic medium.
AB  - Two pure minerals and a hydrophobic medium were selected to study sorption of
      pharmaceuticals. The sorption of four pharmaceuticals, acetaminophen (analgesic),
      17alpha-ethynyl estradiol (synthetic hormone), nalidixic acid (antibiotic), and
      norfloxacin (antibiotic), was evaluated with silica, alumina, and Porapak P (a
      hydrophobic medium). Alumina and silica were selected to represent positively
      charged and negatively charged aquifer mineral surfaces at neutral pH,
      respectively, while Porapak P was selected to represent the hydrophobic organic
      content of an aquifer medium. At neutral pH, acetaminophen, the least hydrophobic
      pharmaceutical, showed no significant sorption to any of the media, while 17alpha
      ethynyl estradiol, the most hydrophobic pharmaceutical, showed significant
      sorption to Porapak P. Nalidixic acid, which has a carboxyl functional group that
      is anionic at neutral pH, showed significant adsorption to the positively charged
      alumina. Norfloxacin, with both a carboxyl (anionic) and a piperazynyl (cationic)
      group, can exist in four forms (neutral, cationic, anionic, and zwitterionic)
      depending on the aqueous pH. Norfloxacin also showed significant adsorption than
      nalidixic acid. Both nalidixic acid and norfloxacin adsorbed to silica and
      Porapak P to a much lower extent. The pH dependence of nalidixic acid and
      norfloxacin adsorption to silica and alumina was also studied by varying the pH
      between 4 and 11. The maximum adsorption of nalidixic acid to alumina occurred
      near its pKa (pH approximately 6), where the combination of cationic alumina and
      anionic nalidixic produced maximum adsorption. The maximum adsorption of
      norfloxacin to alumina was observed at pH approximately 7, which was the region
      where the zwitterionic form dominated. This research demonstrates that the
      adsorption of ionizable pharmaceuticals is strongly dependent on the system pH,
      the pharmaceutical properties (pKa and hydrophobicity), and the nature of the
      surface charge (point of zero charge). For pharmaceuticals that are uncharged at
      environmentally relevant pH values, the main sorption factor is their solubility
      or hydrophobicity; for charged forms, ion exchange is also an important
      adsorption mechanism.

PMID- 16563462
TI  - Anaerobic digestion of tannery soak liquor with an aerobic post-treatment.
AB  - The leather industry occupies a place of prominence in the Indian economy due to
      its massive potential for employment, growth and exports. The potential
      environmental impact of tanning is significant. This study focuses on tannery
      soak liquor, generated by the soaking of hides and skins, which is characterised
      by high organic load and high salinity. For these reasons, the soak liquor should
      be segregated and pre-treated separately before being mixed with the composite
      wastewater, made of all other streams mixed together. The anaerobic digestion of
      tannery soak liquor was studied using a UASB. COD removal reached 78% at an OLR
      of 0.5 kg COD m(-3) d(-1), a HRT of 5 days and a TDS concentration of 71 gl(-1).
      The combination of the UASB with an aerobic post-treatment enhanced the
      performance of the overall wastewater treatment process and the COD removal
      efficiency of the combined anaerobic/aerobic treatment system reached 96%.
      However, for effective operation, the system had to be operated at very low OLRs,
      which affects the economic viability of such a process.

PMID- 16563463
TI  - Photocatalytic oxidation and removal of arsenite from water using slag-iron oxide
      TiO2 adsorbent.
AB  - Photocatalytic oxidation of arsenite and simultaneous removal of the generated
      arsenate from aqueous solution were investigated. The whole process was performed
      using an adsorbent developed by loading iron oxide and TiO2 on municipal solid
      waste melted slag. The loading was carried out through chemical reactions and
      high-temperature process. In the removal process, arsenite was first oxidized to
      arsenate, and then was removed by adsorption. The oxidation of arsenite was
      rapid, but the adsorption of the generated arsenate was slow. A concentration of
      100 mg l(-1) arsenite could be entirely oxidized to arsenate within 3 h in the
      presence of the adsorbent and under UV-light irradiation, but the equilibrium
      adsorption of the generated arsenate needed 10 h. Arsenite could also be oxidized
      to arsenate only by UV-light, but the reaction rate was approximately 1/3 of that
      of the photocatalyzed reaction. Both acidic and alkaline conditions were
      favorable for the oxidation reaction, and the optimum pH value for the oxidation
      and adsorption was proposed to be around 3. To oxidize and remove original 20 mg
      l(-1) or 50 mg l(-1) arsenite from aqueous solution, the necessary adsorbent
      amount was 2 g l(-1) or 5 g l(-1), respectively. Furthermore, the surface
      properties of the adsorbent were examined and the oxidation mechanism of arsenite
      was discussed. It is believed that the adsorbent developed in this study is
      efficient, cost-effective and environment-friendly for application in arsenic
      contaminated wastewater treatment.

PMID- 16563464
TI  - Accumulation of Hg and other heavy metals in the Javan mongoose (Herpestes
      javanicus) captured on Amamioshima Island, Japan.
AB  - Concentrations of 22 elements (Mg, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr,
      Mo, Ag, Cd, Sb, Cs, Ba, Tl, total Hg (T-Hg), Pb) and organic Hg (O-Hg) were
      examined in the liver, kidney and brain of the Javan mongoose (Herpestes
      javanicus) and in liver of the Amami rabbit (Pentalagus furnessi) from
      Amamioshima Island in Japan. Relatively high levels of T-Hg levels (from 1.75 to
      55.5 microg g-1 wet wt.) were found in the Javan mongoose. As for a comparison of
      hepatic T-Hg concentrations between the two areas, there was no significant
      difference between the Javan mongoose in Amamioshima and those in the Okinawa
      islands. In addition, T-Hg levels in the livers of the Amami rabbit were the same
      as in the livers of other herbivorous mammals. Taken together, it suggested that
      T-Hg accumulation in the livers of the Javan mongoose was not affected by the
      environment but by a specific physiological mechanism. The comparison of Hg and
      other heavy metal accumulations between terrestrial mammals (13 species, 61
      individuals) including the Javan mongoose and marine mammals (18 species, 508
      individuals) were also discussed.

PMID- 16563465
TI  - Degradation of microcystins using immobilized microorganism isolated in an
      eutrophic lake.
AB  - The final purpose of our series of studies is to establish a biological removal
      method of cyanobacteria and their toxic products using immobilized microorganisms
      that can lyse cyanobacteria and decompose microcystins. To establish the
      biological removal method in non-point areas and water purification plants, as
      the first step, we explored bacteria active against the cyanobacterial
      hepatotoxin microcystin in the present study. Eleven active bacteria were
      isolated from samples taken from Lakes Tsukui and Sagami, Japan. Among 3 strains
      (B-9 to B-11) with degradative activity, strain B-9 exhibited the strongest
      activity. The 16S rDNA sequence of the strain B-9 showed the highest similarity
      to that of Sphingomonas sp. Y2 (AB084247, 99% similarity). Microcystins-RR and 
      LR were completely degraded by strain B-9 (SC16) within 1d, which led to an
      immobilized microorganism with a polyester resin. The degradation of microcystin
      RR in a bioreactor using the immobilized strain B-9 was observed and microcystin
      RR (> 90%) was completely degraded after 24 h. Microcystin-RR was added to the
      lake water at regular intervals and the degradation after 24 h was observed in
      the bioreactor over a 72-d period. An over 80% removal efficiency continued for 2
      months, showing that the life of the immobilized B-9 in terms of activity was at
      least 2 months under the optimized conditions. From these results, this
      immobilized B-9 is feasible for the practical treatment of microcystins in non
      point areas and water purification plants.

PMID- 16563466
TI  - Mild hydrolysis of 2-trifluoromethylphenol: kinetics, mechanism and environmental
      relevance.
AB  - 2-Trifluoromethylphenol was hydrolysed in a phosphate buffer at neutral pH. At
      mild temperatures ranging from 34 degrees C to 69 degrees C this compound
      liberates consecutively fluorine anions to form salicylic acid. This process is
      energetically driven by the hydration of the fluorine anions. No intermediates
      have been detected by HPLC and (19)F-NMR and this was confirmed by computer
      calculations which favor the first step in the whole reaction sequence being rate
      limiting. Accordingly, the reaction energy of the first dehalogenation of the
      trifluoromethyl anion is 28.4 kcal mol(-1) higher than for the second
      dehalogenation. The pseudo-first-order kinetic was determined and from an
      Arrhenius diagram an activation energy of E(a)=25.1 kcal mol(-1) has been
      estimated. At 37 degrees C and a pH of 7.4 the half-life was 6.9 h. The rate of
      hydrolysis was favored at higher pH and it was not influenced by oxygen, sunlight
      or trace elements found in natural water. The latter was shown by incubations
      with lake water instead of distilled water.

PMID- 16563467
TI  - Contours of the hominoid lateral tibial condyle with implications for
      Australopithecus.
AB  - Tibial condyle shape is alleged to vary among fossil tibiae attributed to
      Australopithecus, and has been argued to reflect functional differences of the
      knee. Convex anteroposterior curvature of the lateral tibial condyle in A.
      africanus has been interpreted to indicate a more chimpanzee-like locomotor
      repertoire than the flatter lateral tibial condyles of A. afarensis (Berger and
      Tobias, 1996, J. Hum. Evol. 30, 343). Alternatively, Latimer, Ohman, and Lovejoy
      (1987, Am. J. Phys. Anthropol. 74, 155) have suggested that in response to
      increased transarticular loads accompanied by larger body mass, joints should
      become flatter as size increases, both within and among species, so that the
      variation observed among hominin fossils reflects size alone rather than
      functional differences. In this study, three-dimensional surface areas of the
      lateral tibial condyle of humans, chimpanzees, and gorillas were computed using a
      Digibot II (Digibotics) laser scanner and the DataSculpt v.4.6 engineering
      software package to evaluate joint surface contours, and compared to two
      dimensional surface area and arc and chord length measurements of the
      anteroposterior and mediolateral axes. Extant species measurements were then
      compared to those of A. afarensis (A.L. 129-1b, A.L. 288-1aq, A.L. 333x-26, A.L.
      333-42) and A. africanus (Stw 514a). Results do not support the hypothesis that
      A. afarensis and A. africanus differ in condylar topology. They also do not
      support the hypothesis that joint surfaces become flatter with increased
      transarticular load accompanying increased body size, as curvature of the lateral
      tibial condyle in anteroposterior and mediolateral planes is not negatively
      allometric. However, femoral condylar shape is not included in this study, which
      may better reflect joint surface responses to increased body size. Finally, there
      is no basis from this study to reconstruct differences in locomotor behavior
      among fossil hominin taxa based on lateral tibial condyle morphology.

PMID- 16563468
TI  - Mandibular size and shape variation in the hominins at Dmanisi, Republic of
      Georgia.
AB  - The hominin fossils of Dmanisi, Republic of Georgia, present an ideal means of
      assessing levels of skeletal size and shape variation in a fossil hypodigm
      belonging to the genus Homo because they have been recovered from a spatially and
      temporally restricted context. We compare variation in mandible size and shape at
      Dmanisi to that of extant hominoids and extinct hominins. We use height and
      breadth measurements of the mandibular corpus at the first molar and the
      symphysis to assess size, and analyze shape based on size-adjusted (using a
      geometric mean) versions of these four variables. We compare size and shape
      variation at Dmanisi relative to all possible pairs of individuals within each
      comparative taxon using an exact resampling procedure of the ratio of D2600 to
      D211 and the average Euclidean distance (AED) between D2600 and D211,
      respectively. Comparisons to extant hominoids were conducted at both the specific
      and subspecific taxonomic levels and to extinct hominins by adopting both a more,
      and less speciose, hominin taxonomy. Results indicate that the pattern of
      variation for the Dmanisi hominins does not resemble that of any living species:
      they exhibit significantly more size variation when compared to modern humans,
      and they have significantly more corpus shape variation and size variation in
      corpus heights and overall mandible size than any extant ape species. When
      compared to fossil hominins they are also more dimorphic in size (although this
      result is influenced by the taxonomic hypothesis applied to the hominin fossil
      record). These results highlight the need to re-examine expectations of levels of
      sexual dimorphism in members of the genus Homo and to account for marked size and
      shape variation between D2600 and D211 under the prevailing view of a single
      hominin species at Dmanisi.

PMID- 16563469
TI  - Monitoring platelet inhibition after clopidogrel with the VerifyNow-P2Y12(R)
      rapid analyzer: the VERIfy Thrombosis risk ASsessment (VERITAS) study.
AB  - INTRODUCTION: Clopidogrel inhibits platelet P2Y12 ADP receptors, while ADP, as an
      inductor of aggregation, stimulates both P2Y12 and P2Y1 platelet receptors.
      Despite a clinical loading dose routine with clopidogrel, some patients still
      experience coronary stent thrombosis suggesting persistent platelet activation.
      The VerifyNow-P2Y12 is a rapid assay that test platelet activity over 3 min and
      uses of the combination of ADP and prostaglandin E1 (PGE1) to directly measure
      the effects of clopidogrel on the P2Y12 receptor. ADP is used to maximally
      activate the platelets by binding to the P2Y1 and P2Y12 platelet receptors, while
      PGE1 is used to suppress the ADP-induced P2Y1-mediated increase in intracellular
      calcium levels. OBJECTIVE: The VERIfy Thrombosis risk ASsessment (VERITAS) was a
      prospective study designed to measure platelet response to clopidogrel therapy in
      subjects with multiple risk factors or history of vascular disease using this
      novel point-of-care assay. METHODS: 166 participants were enrolled in 4
      participating sites. Data from 147 participants were analyzed after exclusion of
      19 patients due to protocol violations. Platelets were assessed twice at baseline
      (before clopidogrel) and at 24 h post-loading 450 mg (110 participants) or 7 days
      after chronic clopidogrel treatment (75 mg/day) (37 patients). All participants
      received aspirin 81-325 mg for at least 2 days before the study enrollment.
      Results from the VerifyNow-P2Y12 assay are reported in P2Y12 reaction units
      (PRU). RESULTS: Clopidogrel therapy resulted in a mean 64.0+/-25.3% PRU
      reduction. No participant reached PRU inhibition below 10% of baseline.
      Distribution of PRU values for the VerifyNow-P2Y12 assay shows a separation from
      baseline to post-clopidogrel assay values with some overlap due to high inter
      individual variations in response. CONCLUSIONS: VerifyNow-P2Y12 is a reliable,
      fast and sensitive device suitable for monitoring of platelet inhibition during
      clopidogrel therapy.

PMID- 16563470
TI  - Vitamin D and its role in immunology: multiple sclerosis, and inflammatory bowel
      disease.
AB  - Autoimmune diseases like multiple sclerosis (MS) and inflammatory bowel disease
      (IBD) occur because of an inappropriate immune-mediated attack against self
      tissue. Analyses of genetically identical twins shows that besides genetics there
      are important environmental factors that contribute to MS and IBD development.
      Vitamin D availability due to sunshine exposure or diet may play a role in the
      development of MS and IBD. Compelling data in mice show that vitamin D and
      signaling through the vitamin D receptor dictate the outcome of experimental MS
      and IBD. Furthermore, the evidence points to the direct and indirect regulation
      of T cell development and function by vitamin D. In the absence of vitamin D and
      signals delivered through the vitamin D receptor, auto reactive T cells develop
      and in the presence of active vitamin D (1,25(OH)(2)D(3) ) and a functional
      vitamin D receptor the balance in the T cell response is restored and
      autoimmunity avoided.

PMID- 16563471
TI  - Vitamin D physiology.
AB  - Vitamin D3 is synthesized in the skin during summer under the influence of
      ultraviolet light of the sun, or it is obtained from food, especially fatty fish.
      After hydroxylation in the liver into 25-hydroxyvitamin D (25(OH)D) and kidney
      into 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite can enter the
      cell, bind to the vitamin D-receptor and subsequently to a responsive gene such
      as that of calcium binding protein. After transcription and translation the
      protein is formed, e.g. osteocalcin or calcium binding protein. The calcium
      binding protein mediates calcium absorption from the gut. The production of
      1,25(OH)2D is stimulated by parathyroid hormone (PTH) and decreased by calcium.
      Risk factors for vitamin D deficiency are premature birth, skin pigmentation, low
      sunshine exposure, obesity, malabsorption and advanced age. Risk groups are
      immigrants and the elderly. Vitamin D status is dependent upon sunshine exposure
      but within Europe, serum 25(OH)D levels are higher in Northern than in Southern
      European countries. Severe vitamin D deficiency causes rickets or osteomalacia,
      where the new bone, the osteoid, is not mineralized. Less severe vitamin D
      deficiency causes an increase of serum PTH leading to bone resorption,
      osteoporosis and fractures. A negative relationship exists between serum 25(OH)D
      and serum PTH. The threshold of serum 25(OH)D, where serum PTH starts to rise is
      about 75nmol/l according to most surveys. Vitamin D supplementation to vitamin D
      deficient elderly suppresses serum PTH, increases bone mineral density and may
      decrease fracture incidence especially in nursing home residents. The effects of
      1,25(OH)2D and the vitamin D receptor have been investigated in patients with
      genetic defects of vitamin D metabolism and in knock-out mouse models. These
      experiments have demonstrated that for active calcium absorption, longitudinal
      bone growth and the activity of osteoblasts and osteoclasts both 1,25(OH)2D and
      the vitamin D receptor are essential. On the other side, bone mineralization can
      occur by high ambient calcium concentration, so by high doses of oral calcium or
      calcium infusion. The active metabolite 1,25(OH)2D has its effects through the
      vitamin D receptor leading to gene expression, e.g. the calcium binding protein
      or osteocalcin or through a plasma membrane receptor and second messengers such
      as cyclic AMP. The latter responses are very rapid and include the effects on the
      pancreas, vascular smooth muscle and monocytes. Muscle cells contain vitamin D
      receptor and several studies have demonstrated that serum 25(OH)D is related to
      physical performance. The active metabolite 1,25(OH)2D has an antiproliferative
      effect and downregulates inflammatory markers. Extrarenal synthesis of 1,25(OH)2D
      occurs under the influence of cytokines and is important for the paracrine
      regulation of cell differentiation and function. This may explain that vitamin D
      deficiency can play a role in the pathogenesis of auto-immune diseases such as
      multiple sclerosis and diabetes type 1, and cancer. In conclusion, the active
      metabolite 1,25(OH)2D has pleiotropic effects through the vitamin D receptor and
      vitamin D responsive elements of many genes and on the other side rapid non
      genomic effects through a membrane receptor and second messengers. Active calcium
      absorption from the gut depends on adequate formation of 1,25(OH)2D and an intact
      vitamin D receptor. Bone mineralization mainly depends on ambient calcium
      concentration. Vitamin D metabolites may play a role in the prevention of auto
      immune disease and cancer.

PMID- 16563472
TI  - International commission on non-ionizing radiation protection.

PMID- 16563473
TI  - Does pretreatment human papillomavirus (HPV) titers predict radiation response
      and survival outcomes in cancer cervix?--a pilot study.
AB  - OBJECTIVE: To evaluate if pretreatment HPV titers in cancer cervix could predict
      radiation response and survival outcomes. METHODS: Twenty-one patients of cancer
      cervix were treated by radiotherapy (RT) alone. HPV titers were estimated using
      DNA Hybrid Capture II test. Loco-regional response at 1 month of RT--complete or
      partial response (CR and PR respectively) and survival outcomes--local disease
      free (LDFS), disease-free (DFS) and overall (OS) survivals were evaluated against
      pre- and posttreatment HPV titers. RESULTS: Pretreatment HPV titers ranged from
      0.81 to 3966.10 RLU/cut off (mean +/- SD: 1264.39 +/- 1148.22, median: 1129.98).
      Of the demographic features evaluated, mean HPV titers were significantly
      different only for patients achieving CR or PR at completion of RT (mean +/- SD
      for CR vs. PR: 1616.31 +/- 1146.86 vs. 384.57 +/- 538.80, P = 0.022). HPV titers
      at end of RT ranged from 0.12 to 487.42 RLU/cut off (mean +/- SD: 37.31 +/-
      108.60, median: 2.33). Patients with higher pretreatment HPV titers (>1000
      RLU/cutoff) had a higher CR (P = 0.022) and better survival compared to those
      with < or =1000 RLU/cutoff (LDFS, P = 0.004; DFS, P = 0.005; OS, P = 0.012). At
      completion of RT, those having > or =99.5% fall in HPV had superior survival
      outcomes than those with <99.5% reduction (LDFS, P = 0.002; DFS, P = 0.002; OS, P
      = 0.004). CONCLUSIONS: Higher pretreatment HPV titers (>1000 RLU/cutoff) could be
      considered as a predictor of radiotherapy response and survival in cancer cervix.
      A reduction in these titers to 99.5% of their baseline values at end of
      radiotherapy is also associated with better survival outcomes.

PMID- 16563474
TI  - Expression of muscarinic and dopaminergic receptors and monoamine levels frontal
      cortex of epileptic rats.
AB  - Apart from stroke, epilepsy is the most common neurological disorder with 0.5% of
      prevalence. The present study was performed in order to determine the monoamine
      levels, (M(1)-like) muscarinic and (D(1)- and D(2)-like) dopaminergic receptor
      changes in frontal cortex of adult rats after pilocarpine-induced status
      epilepticus (SE). Male Wistar rats were treated with a single dose of pilocarpine
      (400 mg/kg, s.c.) and the control group received 0.9% saline (s.c.). Both groups
      were sacrificed 1 h after treatment. The frontal cortex was dissected for
      neurochemical assays. The results show a downregulation of 27% in M(1) muscarinic
      receptor density, but in the dissociation constant (K(d)) value remained
      unaltered. D(1) and D(2) dopaminergic receptor densities and their K(d) values
      remained unaltered. Monoamine and metabolites levels presented decreases of 44%,
      27%, 30% and 42% in dopamine (DA), homovanilic acid (HVA), norepinephrine (NE)
      and 5-hydroxyindoleacetic acid (5-HIAA) contents, respectively. Moreover, in
      serotonin (5-HT) level remained unaltered and the 4-hydroxy-3-methoxy
      phenylacetic acid (DOPAC) concentration was augmented by 34%. The results suggest
      that dopaminergic system in this area studied may not be directly involved in the
      seizures and status epilepticus, but different monoamines and metabolites can be
      modified in this cerebral area during seizure process. In conclusion, the
      neurochemical alterations that occur in frontal cortex of adult rats observed
      during the establishment of the status epilepticus induced by pilocarpine are
      decrease in M(1) receptor density concentration and a reduction in DA and NE
      levels.

PMID- 16563475
TI  - Antinociceptive and behavioral effects of ribavirin in mice.
AB  - The antinociceptive effect of ribavirin, an antiviral drug, was studied after
      systemic injection using several pain tests in mice. In the hot-plate test of
      thermal pain, capsaicin-induced chemogenic pain, formalin test and abdominal
      stretching assay induced by the i.p. injection of 0.6% acetic acid, ribavirin
      produced a dose-related reduction in nociceptive responses. The visceral
      antinociceptive effect of ribavirin was unaffected by co-treatment with
      yohimbine, atropine or theophylline, but partially reversed by naloxone.
      Antinociception by ribavirin was augmented by treatment with prazosin, doxazosin,
      propranolol, guanethidine, glibenclamide, baclofen, indomethacin or cysteamine.
      Further, the ribavirin induced antinociception was enhanced by D2 receptor
      antagonists haloperidol, sulpiride, clozapine or domperidone and by the dopamine
      D2 receptor agonist bromocryptine. Ribavirin did not exhibit depression-like
      effect, nor it influenced the effect of amitriptyline in the forced swimming
      test. It did not impair cognitive performance in the Morris water Maze test. The
      present data demonstrate that ribavirin administered via systemic route possesses
      visceral and thermal anti-nociceptive properties. The ribavirin analgesic effect
      was partially reversed by naloxone, an opioid antagonist.

PMID- 16563476
TI  - An inter-gender effect on ethanol drinking in rats: proximal females increase
      ethanol drinking in males.
AB  - Three groups of male Long-Evans hooded rats were assessed for effects of social
      opportunity on drinking of ethanol or water. The ethanol/female group received
      intermittent presentations of a sipper containing ethanol that was followed by 15
      s of social interaction opportunity with a female rat. The ethanol/male group
      received similar training except the social interaction opportunity was with a
      male rat. The water/female group received training similar to the ethanol/female
      group except that the sipper contained water. For the ethanol groups, the
      concentration of ethanol [3%, 4%, 6%, 8% and 10% (vol/vol)] in the sipper was
      increased across sessions. With 10% ethanol in the sipper, social opportunity
      with females induced more drinking and ethanol intake than did social opportunity
      with males. Social opportunity with females induced more intake of ethanol than
      water. Post-session plasma samples revealed social opportunity with females
      induced higher corticosterone and testosterone levels than did social opportunity
      with males, irrespective of the sipper fluid. This study documents, for the first
      time, an inter-gender effect on ethanol drinking in rats.

PMID- 16563477
TI  - A role for D2 but not D1 dopamine receptors in the cross-sensitization between
      amphetamine and salt appetite.
AB  - A history of sodium depletions has been found to potentiate the psychomotor as
      well as the rewarding effects of amphetamine, an indirect dopamine agonist. The
      present experiments were conducted to further define the role of dopamine
      receptor subtypes in this cross-sensitization effect. Rats with a history of
      sodium depletions were found to display psychomotor sensitization to a D2 but not
      a D1 direct agonist. Cross-sensitization between salt appetite and amphetamine
      was found to be blocked by a D2 but not a D1 antagonist. Together, these results
      implicate D2 but not D1 receptor function in the cross-sensitization seen after
      sodium depletions.

PMID- 16563478
TI  - Tobacco smoke overload and ethnic, state, gender, and temporal cancer mortality
      disparities in Asian-Americans and Pacific Islander-Americans.
AB  - BACKGROUND: Asians and Pacific Islanders (APIs) are important populations
      nationally and globally. So we assessed cumulative tobacco smoke overexposure
      (smoke overload)/cancer mortality associations across states, ethnicities, years,
      and genders among API-Americans. METHODS: Death rates were adjusted to the 2000
      United States age standard, lung cancer death rates used as a smoke overload bio
      index, and lung/non-lung cancer death rate linear regressions run. Cancer death
      rate smoking-attributable fractions (SAFs) are equal to 1--estimated unexposed
      rate/observed rate. RESULTS: The two lowest smoke overload and non-lung cancer
      death rates were in South Asian (Indo)-Californian females and males. The highest
      were in Korean-Californian males. Non-lung cancer death rates were tightly and
      steeply associated with smoke overload across ethnicity, state, year, or gender.
      Cancer death rate smoking-attributable fractions ranged from 0 in female and 6%
      in male Indo-Californians, to 39% in female and 57% in male API-Americans in
      2002, to 71% in Korean-Californian and 69% in API Hawaiian males. DISCUSSION:
      Many API American cancer death rate disparities across genders, ethnicities,
      states, or years can be explained by smoke overload disparities. Tobacco control
      may greatly reduce cancer death rates and disparities among API-Americans and,
      likely, others.

PMID- 16563479
TI  - Trends in colon cancer screening procedures in the US Medicare and Tricare
      populations: 1999-2001.
AB  - BACKGROUND: This study examined trends in the numbers of double contrast barium
      enemas, flexible sigmoidoscopies, and colonoscopies and trends in the choices of
      colorectal cancer screening service providers. METHODS: Descriptive statistics
      were used to examine Medicare and Tricare data for the years 1999 to 2001.
      RESULTS: The total volume of procedures increased 5% and 14%, respectively, in
      Tricare and Medicare. Tricare and Medicare, respectively, saw 32% and 33%
      reductions in barium enemas and 28% and 41% reductions in flexible
      sigmoidoscopies. Colonoscopies increased by 45% and 34% in Tricare and Medicare,
      respectively. Gastroenterologists provided the majority of colonoscopies for both
      groups each year. CONCLUSIONS: The volume of colonoscopies increased from 1999 to
      2001 for both groups while the volumes of barium enemas and flexible
      sigmoidoscopies decreased. Gastroenterologists appear to be the preferred
      providers of colonoscopies.

PMID- 16563480
TI  - Mammography use among older women of seven Latin American and Caribbean cities.
AB  - BACKGROUND: To describe the prevalence of mammography use, and to estimate its
      association with sociodemographics. METHODS: A sample of 6207 women aged 60 and
      older from the first interview of Health, Well-Being and Aging in Latin America
      and the Caribbean Study (SABE) in seven cities (Buenos Aires, Bridgetown, Havana,
      Mexico, Montevideo, Santiago, and Sao Paulo). The outcome was reporting a
      mammogram within the last 2 years. RESULTS: Prevalence of mammography use ranged
      from 9.8% in Havana to 34.4% in Sao Paulo. Independent predictors of mammography
      use across cities were older age (lowest odds ratio [OR] = 0.92, 95% confidence
      interval [CI] 0.89-0.95), higher education (highest OR = 1.14, 95% CI 1.08-1.20),
      public health insurance (lowest OR = 0.28, 95% CI 0.11-0.76), or no insurance
      (lowest OR = 0.08, 95% CI 0.02-0.34) compared with private insurance. In a
      combined sample of six cities, higher education was associated with higher
      mammography use, but older age and insurance (public: OR = 0.54, 95% CI 0.45
      0.65; no insurance: OR = 0.30, 95% CI 0.23-0.40; compared with private insurance)
      were associated with lower mammography use. CONCLUSIONS: Prevalence of
      mammography use across cities was lower than that reported for Hispanic
      populations in the US. In the overall sample, mammography use was increased in
      highly educated people and decreased in people without insurance.

PMID- 16563481
TI  - Problem drinking: rural and urban trends in America, 1995/1997 to 2003.
AB  - OBJECTIVE: Studies examining trends in problem alcohol use for U.S. adults
      residing in rural locations are lacking. This study examines recent trends in
      heavy and binge drinking in urban counties and three types of rural counties.
      METHODS: Random-digit telephone survey of adults aged 18 years or older residing
      in states participating in the Behavioral Risk Factor Surveillance System, in the
      years 1995/1997 (n = 247,255), 1999/2001 (n = 362,077) and 2003 (n = 257,659).
      Analyses were performed in 2006. RESULTS: Metropolitan counties experienced
      higher prevalence of heavy and binge drinking than rural counties in all years,
      and all geographic areas showed upward trends in both drinking behaviors. Trends
      in heavy drinking were sharper in rural counties (3.8% to 5.4% compared with 4.9%
      to 6.0% in metro counties). Metropolitan and rural counties overall saw similar
      increases in binge drinking, however, the greatest increase occurred in remote
      micropolitan counties (12.7% to 15.7%). CONCLUSION: Heavy and binge drinking are
      problems that continue to increase in rural areas nationwide. Because of the
      difficulties inherent in accessing and administering substance abuse treatment in
      rural areas, special attention should be given to tailoring alcohol abuse
      interventions to the needs of rural residents.

PMID- 16563482
TI  - Psychological and behavioral impact of receipt of a "normal" ovarian cancer
      screening test.
AB  - OBJECTIVE: While cancer screening can reduce morbidity and mortality, screening
      can also be associated with adverse physical, psychological, and behavioral
      outcomes, even when no malignancy is detected. Few studies, however, have
      comprehensively examined the potential positive impact of a normal cancer
      screening test result. This study examined the effects of receipt of a normal
      ovarian cancer screening test result on a range of psychosocial outcomes,
      including screening-related beliefs and intentions, risk knowledge, distress, and
      positive affect. METHOD: The present study utilized baseline, 2-week, and 4-month
      data from a sample of 560 asymptomatic women who underwent a routine screening
      for ovarian cancer and received a normal result as well as 296 controls
      (Lexington, Kentucky, USA, 2000-2002). RESULTS: Growth curve modeling revealed
      that receipt of a "normal" test result following ovarian cancer screening was
      associated with increased beliefs in the efficacy of ovarian cancer screening,
      decreased ovarian cancer-related distress, increased knowledge of ovarian cancer
      risk factors, and increased positive affect over the 4-month study period.
      CONCLUSION: Receipt of a normal ovarian cancer screening test result influences a
      range of affective and cognitive endpoints. For the most part, these endpoints
      are either empirically or theoretically linked to likelihood of participation in
      future cancer screening. Thus, participation in routine ovarian cancer screening
      with receipt of a normal screening test result may create a set of affective and
      cognitive conditions that facilitate repeat screening and contribute to the
      maintenance of appropriate ovarian cancer screening behavior.

PMID- 16563483
TI  - Insight into the causes of the recent secular trend in pediatric obesity: Common
      sense does not always prevail for complex, multi-factorial phenotypes.
AB  - Although the secular increase in pediatric obesity is well-documented, there has
      been no serious attempt to systematically address the causes of this secular
      trend. The aim of this paper is to provide a better understanding of the possible
      causes of the recent secular increase in pediatric obesity by reviewing and
      synthesizing the available literature pertaining to the topic. The paper
      addresses caveats and important considerations regarding the body mass index,
      physical activity, and diet and also considers alternative explanations (stress,
      sleep, maternal health, epigenetic mechanisms) for the secular trend. It is
      likely that the increased BMI is due to both an increased fat-free mass and fat
      mass (including waist circumference). Although total caloric intake has remained
      unchanged, there was a clear trend in increased simple sugar consumption. It is
      conceivable that total energy expenditure has decreased because of a decline in
      spontaneous but not voluntary physical activity. Several indicators of psycho
      social stress (antidepressant medication prescriptions and suicide attempts,
      anxiety) have increased along with a decreased sleep duration. Finally, there is
      intriguing evidence that suggests that the secular trend is related to a common
      origin in fetal life that is exacerbated by postnatal events/stressors. The
      insight gained from examining the possible causes of the trend provides a better
      understanding of the basic etiology of pediatric obesity and should be
      incorporated into prevention and intervention models.

PMID- 16563484
TI  - A novel apical midpiece defect in the spermatozoa of a bull without an apparent
      decrease in motility and fertility. A case study.
AB  - Despite some limitations as predictors of fertility, evaluation of sperm
      morphology and progressive motility is the commonest method to assess viability
      of frozen/thawed semen. In this article we describe by light and transmission
      electron microscopy a novel midpiece structural defect observed in 24-36% of
      frozen/thawed sperm cells from a Charolais bull, used in artificial insemination
      programs without any apparent ill effect to the fertility. After thawing, the
      sperm progressive motility ranged from 65 to 80% and the pregnancy rate for all
      artificial inseminations performed (43%) did not differ (p>0.05) from results
      obtained with insemination with semen of other bulls (40%). The defect consisted
      in mitochondrial aplasia at the neck region, mitochondrial segmental elongation
      and gaps and thickening of the outer dense fibers at the apical region of the
      midpiece, and loss of the cementing substance and development of plasma membrane
      extensions in the entire midpiece. No structural abnormalities were found in the
      capitulum, proximal centriole, striated columns, axoneme, annulus and fibrous
      sheath. The thickness of the outer fibers returned to normal at the distal region
      of the midpiece. Based on the examination it is suggested that the alterations
      might be originally caused by loss of the cementing substance that links
      mitochondria to the plasma membrane in association with mitochondrial aplasia at
      the neck region of the midpiece. The abnormality appeared not related to other
      described sperm defect syndromes, although it shared particular characteristics
      with the dag defect, segmental aplasia of the mitochondrial sheath, corkscrew
      defect and pseudodroplet defect.

PMID- 16563485
TI  - The carnivore pregnancy: the development of the embryo and fetal membranes.
AB  - The aim of this research was to compare the morphological aspects during the
      development of pregnancy in dogs and cats, distinguishing features of the fetal
      membranes, such as yolk sac evolution and differentiation of hemangioblasts, and
      the degree of elaboration of the amnion and allantois. Canine and feline
      placentae from 20, 24, 35, 45 and 55 d of pregnancy were perfusion-fixed for
      histological investigation and vascular corrosion casts were produced. The casts
      were prepared for scanning electron microscopy (SEM) and the embryo and fetal
      membrane development was analyzed. The growth patterns of the conceptuses were
      compared with the organization of the placentation process, and changes of the
      morphology during pregnancy were recorded. In feline placentae, an incomplete
      zonary shape was present in 62.5% out of 60 studied cases. This was located
      distal to the insertion of the umbilical cord. In the lamellar zone, the
      interhemal membrane or placental barrier resembled endotheliochorial conditions,
      and the maternal-fetal microvascular blood flow interrelationship was of simple
      crosscurrent type. Dogs have a zonary placenta, completely surrounding the fetus,
      and complex lamellar organization of maternal and fetal tissues. At the border,
      two marginal hematomes with green colouration delimited the central placental
      girdle. The yolk sac consisted of one large sacculation with an inverted "T"
      shape and an enormous number of blood vessels; it had hemangioblast cells in
      contact with the epithelium. The amnion was avascular in early stages, but became
      vascularized by blood vessels of the internal allantoic membrane in later stages
      of pregnancy by intrinsic relation.

PMID- 16563486
TI  - Effect of various photoperiods on testicular weight, weekly sperm output and
      plasma levels of LH and testosterone over the reproductive season in male
      turkeys.
AB  - The effects of duration and variation in photoperiod on testis weight, testicular
      sperm production, semen output, and hormone status over the reproductive season
      in male turkeys were investigated. In Experiment 1, four groups of males raised
      from 17 to 23 wk of age under a constant short photoperiod were subjected to a
      constant short (Group 1: 7L:17D; Group 2: 10.5L:13.5D), constant long (Group 3:
      14L:10D) or progressively increasing photoperiod (Group 4: 7L:17D to 14L:10D) up
      to 60 wk of age. In Experiment 2, four groups of males first raised as in
      Experiment 1 up to 23 wk of age were placed under a constant short (Group 5:
      10.5L:13.5D), constant long (Group 6: 14L:10D), or night-interrupted photoperiod
      (Group 7: 6L:2.5D:1L:14.5D, referred to as subjective 9.5L:14.5D; Group 8:
      6L:3.5D:1L:13.5D), referred to as subjective 10.5L:13.5D) up to 60 wk of age.
      Males in Groups 2-4 had similar reproductive characteristics, whereas sexual
      maturity was delayed from 29 to 49 wk in males from Group 1. In Experiment 2,
      males in Groups 5 and 8 had similar reproductive characteristics, whereas sexual
      maturity was delayed in males in Group 7 in a manner similar to that observed in
      Group 1. In both experiments, plasma LH and testosterone concentrations were poor
      indicators of testis development and semen production, irrespective of age and
      photoperiod. We conclude that a moderately short photoperiod such as 10.5L:13.5D
      or subjective 10.5L:13.5D may stimulate reproductive characteristics of male
      turkeys in a manner comparable to constant long or increasing photoperiods. We
      inferred the existence of a threshold of photosensitivity in male turkeys for
      photoperiods longer than 9.5L:14.5D, but shorter than or equal to 10.5L:13.5D.

PMID- 16563487
TI  - Clinical, biological and hormonal study of mid-pregnancy termination in cats with
      aglepristone.
AB  - In order to evaluate the efficacy, the safety and the variation in plasma
      concentrations of estrogens, progesterone, PGFM, oxytocin, cortisol and prolactin
      after mid-pregnancy termination induced by aglepristone, 61 pregnant queens (33.3
      + 4.2 days), were injected subcutaneously with 15 [corrected] mg/kg aglepristone,
      (Alizine) [corrected] repeated once 24 h later. Five queens served as control and
      received a placebo. The efficacy of aglepristone was 88.5% and termination of
      pregnancy was achieved in 50% of the queens within 3 days. Brief periods of
      depression and anorexia were noted in 9.3% of the queens before fetal expulsion
      (these symptoms were attributed to the phenomenon of fetal expulsions). Not one
      of the queens that aborted developed uterine disease. There were no changes in
      plasma concentrations of estrogen, prostaglandin, prolactin or oxytocin following
      aglepristone administration. However, there were significant increases in plasma
      concentrations of progesterone and cortisol 60 and 30 h, respectively, after
      aglepristone administration. Termination of pregnancy occurred with high plasma
      progesterone concentrations. Fetal expulsion was characterised by an increase in
      estrogen, PGFM and oxytocin concentrations, whereas prolactin and cortisol levels
      remained at a basal level.

PMID- 16563488
TI  - Challenges in cryopreservation of clouded leopard (Neofelis nebulosa)
      spermatozoa.
AB  - The clouded leopard (Neofelis nebulosa) is an endangered species that is
      difficult to breed in captivity. Species management could benefit from the use of
      artificial insemination (AI) with frozen-thawed spermatozoa, but there have been
      no detailed studies of sperm cryosensitivity. The purposes of this study were to:
      (1) re-characterize seminal characteristics in the clouded leopard 20 years after
      the first descriptive studies Wildt et al., [Wildt DE, Howard JG, Hall LL, Bush
      M. Reproductive physiology of the clouded leopard. I. Electroejaculates contain
      high proportions of pleiomorphic spermatozoa throughout the year. Biol Reprod
      1986; 34: 937-947]; and (2) conduct a comparative cryopreservation study on the
      feasibility of sperm from this species surviving a freeze-thawing stress.
      Ejaculates were collected from five adult males and subjected to standard
      analysis, followed by a two-step straw freezing protocol that evaluated the
      impact of thawing, dilution, centrifugation and in vitro culture (through 4 h) on
      sperm motility and acrosomal integrity. Additionally, we assessed the impact of
      both a traditional permeating cryoprotectant (glycerol at a final dilution of 4%)
      and an unconventional nonpermeating trisaccharide; raffinose (R) at a final
      dilution of 4% or 8%, with or without 4% glycerol on sperm cryosurvival. The
      clouded leopard produced an extremely poor quality ejaculate; although
      approximately 70% of fresh sperm were motile, >80% were malformed. Phase contrast
      microscopy revealed that 40% of all sperm had abnormal acrosomes, but Coomassie
      blue staining indicated that acrosomal abnormalities existed in almost 70% of
      spermatozoa. Upon freeze-thawing, sperm motility declined markedly (P < 0.05) by
      an average of 40%, regardless of diluent used. Interestingly, raffinose was as
      effective as glycerol in protecting both sperm motility and acrosomal integrity.
      Although no acrosomal damage was seen immediately after thawing, < 6%
      morphologically normal intact acrosomes were present by the last measured time
      point. In conclusion, the clouded leopard is a rare felid that (at least in North
      American zoos) is producing extraordinarily poor quality ejaculates. There are so
      many sperm with unexplained deranged acrosomes that it will be particularly
      challenging to use traditional AI with thawed sperm as an adjunct management
      tool.

PMID- 16563489
TI  - Clinical evaluation of the use of aglepristone, with or without cloprostenol, to
      treat cystic endometrial hyperplasia-pyometra complex in bitches.
AB  - The aim of the study was to evaluate the efficacy of aglepristone (10 mg/kg on
      days 1, 2 and 8) for the treatment of metritis or pyometra in bitches (n = 67)
      either alone for cases of metritis (n = 15), or in cases of pyometra (n = 52)
      with (n = 32) or without (n = 20) the addition of low doses (1 microg/kg) of
      cloprostenol for 5 days (days 3-7). Examinations performed on day 90, in addition
      to days 8, 14 and 28, determined that treatments had been curative in the long
      term in 54/67 bitches (80.6%). Bitches in whom pyometra did not resolve, were
      given additional aglepristone on day 14 (n = 38) and day 28 (n = 20).
      Aglepristone alone was curative in 15/15 bitches with metritis. In 17/17 bitches
      with closed pyometra, cervical opening occurred within 48 h of aglepristone
      administration. Amongst the 52 bitches with open (n = 35) or closed (n = 17)
      pyometra, the additional treatment with cloprostenol from days 3 to 7,
      significantly improved the overall success rate at day 90, which was 27/32
      (84.4%), compared to 12/20 (60.0%) in bitches without cloprostenol (P < 0.05).
      The leucocyte count and plasma progesterone concentrations significantly
      decreased over the course of treatment. Thirteen of 15 bitches in whom plasma
      progesterone concentrations were initially low (< 3.18 nmol/L) were cured. The
      recurrence rate after 12 and 24 months was 13.0% (3/23) and 19.0% (4/21),
      respectively.

PMID- 16563490
TI  - Effects of dose and duration of continuous GnRH-agonist treatment on induction of
      estrus in beagle dogs: competing and concurrent up-regulation and down-regulation
      of LH release.
AB  - Dose-response estrus-induction trials were conducted during anestrus in 93
      treated and 6 control bitches, a continuous administration of the GnRH-agonist
      lutrelin with a potency 150 x GnRH, and at six different doses from 0.2 to 4.8
      microg/kg/d for 7-14 days in 15 groups of six to eight dogs each in defined
      stages of natural or pharmacologically determined anestrus. Agonist treatment
      induced clinically and cytologically normal proestrus (in 89% of cases) within
      4.8 +/- 0.2 x days, and resulted in behavioral estrus (71%), spontaneous late
      proestrus LH (and FSH) surges, ovulation (59%) and pregnancy (44%) in a dose
      dependent manner. Outcomes of ovulation and pregnancy in most cases required that
      the dose be sufficiently large enough to routinely stimulate a large initial
      increase in LH and FSH (i.e., > or = 0.6 microg/kg/d), and of sufficient duration
      (i.e., > 7 days) to ensure that supra-basal gonadotropin levels persistedntil no
      longer needed for spontaneous continuation of an induced proestrus. Success
      additionally required that the GnRH dose be modest enough (i.e., < 1.8
      microg/kg/d) to not excessively down-regulate spontaneous pre-ovulatory surge
      release of gonadotropin or be removed shortly before or at the time when the LH
      surges typically occurred (10-13 days after initiation of treatment). The 1.8
      microg dose was compared to saline to assess the time course of its down
      regulation action on serum LH in six ovariohysterectomized bitches compared to
      four saline-related controls. Results in intact bitches receiving the 1.8-microg
      doses demonstrated an LH-releasing effect for 10-11 days that overlapped a period
      of obvious down-regulation seen with the same dose after 3 days in the
      ovariohysterectomized bitches. In the latter, however, complete down-regulation
      to anestrus-like values did not occur until after 18-21 days of treatment. A dose
      of 0.6 microg/kg/d for 12 days yielded the best estrus-induction results,
      including pregnancy rates of 100% in six bitches treated in natural-anestrus
      bitches, six bitches in which anestrus had been advanced by a luteolytic
      prostaglandin treatment and in six bitches in which anestrus had been extended by
      progesterone implants administered for 3 months. Although lutrelin is not
      commercially available, these results provide guidelines for the development of
      estrus-inducing protocols with other GnRH-agonists of known biopotencies.

PMID- 16563492
TI  - Is the wear of dental composites still a clinical concern? Is there still a need
      for in vitro wear simulating devices?
AB  - While once considered a major concern for posterior restorations, wear of dental
      composites has been substantially reduced by changes in formulation and is
      considered today by many to be a solved problem. However, minimal evidence exists
      in the literature to support this conclusion for large restorations, especially
      those involving the replacement of functional cusps, despite the fact that these
      restorations are routinely performed. Evidence shows that wear may be of minimal
      importance for restorations of small to moderate size. However, the literature
      does suggest that failure rates are higher for larger restorations, and that wear
      may still be a significant mode of failure for patients with bruxing and
      clenching habits. In this light, the wear of composites continues to be studied
      by many researchers, and it is justifiable to seek well-defined and reproducible
      in vitro methods for predicting this multifactorial phenomenon.

PMID- 16563493
TI  - The determination of phosphorus containing compounds in dental casting investment
      products by 31P solid-state MAS-NMR spectroscopy.
AB  - OBJECTIVES: To use (31)P solid-state MAS-NMR to determine the phosphorus
      compounds that occur in dental casting investment material: (a) as-received, (b)
      after setting and (c) after burn-out and discover whether such compounds are the
      same in each material across a product range. METHODS: [(1)H] High powered
      decoupling (HPDC) and [(1)H] cross-polarization (CP) (31)P solid-state MAS-NMR
      spectroscopy at a resonance frequency of 121.4 MHz were used. Six commercial
      products were examined. Manufacturer's instructions were followed and a special
      liquid was used without dilution. RESULTS: All products contain ammonium
      dihydrogen phosphate as the acid phosphate required for the setting reaction. All
      set by the formation of struvite and significant amounts of amorphous magnesium
      orthophosphate. In three products, lesser amounts of newberyite were present and
      in another the equivalent amorphous compound was formed. When burnt-out,
      magnesium metaphosphate or pyrophosphate was the dominant matrix compound. A
      higher burn-out temperature favoured pyrophosphate formation. Farringtonite was
      present to a lesser extent with the metaphosphate. SIGNIFICANCE: Compounds that
      were not detected in earlier X-ray powder diffraction spectroscopy studies were
      detected by NMR, notably amorphous and glassy compounds (magnesium orthophosphate
      in set investment and magnesium metaphosphate in burnt-out material). The
      variation between products was significant and far greater than expected from the
      published scientific literature. Since the formation of compounds is affected by
      technical procedure and ambient conditions, these findings could offer some
      insight into the cause of the unpredictability of expansion measurements between
      laboratories. Further research is being undertaken.

PMID- 16563494
TI  - Preparation, properties and controlled release behaviors of pH-induced
      thermosensitive amphiphilic gels.
AB  - Two pH-induced thermosensitive amphiphilic gels for controlled drug release were
      constructed with thermosensitive poly(N-isopropylacrylamide) (PNIPAm) and
      hydrophobic poly(ethyl acrylate) (PEA) by interpenetrating polymer network (IPN)
      technology. To obtain pH-induced thermosensitive functionality at physiological
      temperature, 5 mol % of acrylic acid (AAc) and N, N-dimethyl aminoethyl
      methacrylate (DMA) were incorporated into PNIPAm chain by their copolymerization.
      It is found that the IPN hydrogels show pH-induced thermosensitivity at
      physiological temperature. When the amphiphilic gels with IPN structure were
      immersed in water, the hydrophobic moieties formed by PEA have the potential to
      act as reservoirs for hydrophobic drugs, from which drug may be released slowly.
      Using drug daidzein (DAI) as a model molecule, controlled release behaviors of
      the IPNs were investigated. It is found that the presence of permanently
      hydrophobic PEA network can indeed slow the release rate of DAI and to some
      extent overcome disadvantageous burst effect of PNIPAm-based networks in
      hydration state. The release kinetics of DAI from the IPNs seems to follow pseudo
      zero-order release character, regardless of the hydrogels in swollen or shrunken
      state.

PMID- 16563495
TI  - Combinatorial screen of the effect of surface energy on fibronectin-mediated
      osteoblast adhesion, spreading and proliferation.
AB  - In order to accelerate tissue-engineering research, a combinatorial approach for
      investigating the effect of surface energy on cell response has been developed.
      Surface energy is a fundamental material property that can influence cell
      behavior. Gradients in surface energy were created by using an automated stage to
      decelerate a glass slide coated with a self-assembled monolayer (SAM, n
      octyldimethylchlorosilane) beneath a UV lamp such that the SAM is exposed to the
      UV-light in a graded fashion. UV exposure causes oxidation of the SAM such that a
      longer exposure correlates with increased hydrophilicity. This approach yielded
      substrates having a linear gradient in surface energy ranging from 23 to 62 mN/m
      (water contact angles ranging from 25 degrees to 95 degrees ). Using the gradient
      specimen approach enables all surface energies from 23 to 60 mN/m to be screened
      on each slide. Before cell culture, surface energy gradients were coated with
      fibronectin to allow a study of the effect of surface energy on fibronectin
      mediated cell response. Cells were seeded on the fibronectin-coated gradients and
      adhesion, spreading and proliferation were assessed with automated fluorescence
      microscopy. Surface energy did not affect initial cell adhesion at 8h. However,
      the rate of proliferation was linearly dependent on surface energy and increased
      with increasing hydrophobicity. Cell spread area was unaffected by changes in
      surface energy over the majority of the gradient although cells were
      significantly smaller on the most hydrophilic region. These results show that
      fibronectin-mediated cell spreading and proliferation are dependent on surface
      energy and establish a new combinatorial approach for screening cell response to
      changes in surface energy.

PMID- 16563496
TI  - Cluster analysis and gene expression profiles: a cDNA microarray system-based
      comparison between human dental pulp stem cells (hDPSCs) and human mesenchymal
      stem cells (hMSCs) for tissue engineering cell therapy.
AB  - We investigated gene expression patterns and functional classifications regarding
      the clusters of human dental pulp stem cells (hDPSCs) and human mesenchymal stem
      cells (hMSCs)--which possess a multipotent ability--because little is known about
      the precise moleculobiological clues by which these cells activate their
      differentiating ability or functionality to eventually form dentin and bone,
      respectively. We first verified the expressions of the alkaline phosphatase (ALP)
      gene, dentin matrix protein 1 (DMP-1), and dentinsialophosphoprotein (DSPP) by
      real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and
      consequently discovered the high expressions of these genes. Total RNA was also
      followed by hybridization with a human microarray system consisting of 12,814
      genes. Analyses of gene expression patterns indicated several genes which encode
      extracellular matrix components, cell adhesion molecules, growth factors, and
      transcription regulators. Functional and clustering analyses of differences in
      gene expression levels revealed cell signaling, cell communication, or cell
      metabolism. In the future, information on the gene expression patterns of hDPSCs
      and hMSCs might be useful in determining the detailed functional roles of the
      relevant genes and applicable to stem cell therapies, and these cells could also
      be used as multipotent cell sources for gene technology and tissue engineering
      technology.

PMID- 16563497
TI  - The effect of particulate material on the regulation of chemokine receptor
      expression in leukocytes.
AB  - Cellular chemotaxis is one of the most significant components of the host
      response to implanted materials. However, the effect of materials and their
      particulates on the regulation of chemokine receptor expression is not well
      known. This study investigated the effects of alloy particulates on the
      regulation of CXCR1 and CXCR2 expression on leukocytes from whole blood and
      purified leukocyte cultures. The volumetric particle concentration and
      opsonisation dependent manner of CXCR1 and CXCR2 expression on neutrophils and
      CCR1 and CCR2 expression on monocytes/macrophages was analysed using both flow
      cytometry (FACS) and real time-PCR. Variation in volumetric concentrations of
      particulates demonstrated that cell:particulate ratios of 1:1 of non-opsonised
      NiCr alloy induced the down regulation of CXCR1, and 1:0.25 of opsonised NiCr
      induced the up regulation of CXCR2. CoCr alloy particulates had no effect on CXCR
      expression. This study demonstrated that the regulation of chemokine receptor
      expression could be effected by the properties of materials and the expression of
      these receptors may contribute to host cellular reactions such as chemotaxis.
      This study also demonstrated that the response of leukocytes can be demonstrated
      using a whole blood assay for the study of chemokine receptor expression after
      direct contact with materials.

PMID- 16563498
TI  - Effect of RGD secondary structure and the synergy site PHSRN on cell adhesion,
      spreading and specific integrin engagement.
AB  - The relationship between the form of cell adhesion, ligand presentation, and cell
      receptor function was characterized using model Langmuir-Blodgett supported
      films, containing lipid-conjugated peptide ligands, in which isolated variables
      of the ligand presentation were systematically altered. First, the conformation
      of an adhesive Arginine-Glycine-Aspartic acid (RGD) peptide was varied by
      synthesizing linear and looped RGD peptide-containing amphiphiles and
      subsequently measuring the impact on the function of human umbilical vein
      endothelial cells. Secondly, the contribution of non-contiguous ligands to
      cellular engagement was assessed using multi-component biomimetic films. The
      peptide amphiphiles were composed of fibronectin-derived headgroups--GRGDSP, and
      its synergy site Pro-His-Ser-Arg-Asn (PHSRN)--attached to hydrocarbon tails. The
      peptide amphiphiles were diluted using polyethylene glycol (PEG) amphiphiles,
      where PEG inhibited non-specific cell adhesion. Cells adhered and spread on
      GRGDSP/PEG systems in a dose-dependent manner. The presentation of GRGDSP
      influenced integrin cell surface receptor specificity. Results demonstrated that
      beta1-containing integrins mediated adhesion to the linear GRGDSP presentation to
      a greater extent than did the alphavbeta3 integrin, and looped GRGDSP
      preferentially engaged alphavbeta3. GRGDSP/PHSRN/PEG mixtures that closely
      mimicked the RGD-PHSRN distance in fibronectin, enhanced cell spreading over
      their two-component analogues. This study demonstrated that controlling the
      microenvironment of the cell was essential for biomimetics to modulate specific
      binding and subsequent signaling events.

PMID- 16563499
TI  - Mechanical and histological evaluation of a PMMA-based bone cement modified with
      gamma-methacryloxypropyltrimethoxysilane and calcium acetate.
AB  - Polymethylmethacrylate (PMMA) bone cement is widely used for prosthetic fixation
      in orthopaedic surgery; however, the interface between bone and cement is a weak
      zone. We developed a bioactive PMMA cement through modification with gamma
      methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. The purpose of this
      study was to compare the handling, mechanical and histological properties of the
      modified bone cement with those of the conventional cement. The modified
      specimens exhibited higher bonding strength between bone and implant.
      Histological observation and micro-focus X-ray computed tomogram (micro-CT)
      images showed that the modified cement exhibited osteoconduction, which the
      conventional PMMA bone cement lacked. The modification was found to be effective
      in enabling osteoconduction with PMMA bone cement, thus providing stable fixation
      for a long period after implantation.

PMID- 16563500
TI  - Influences of extracellular matrix and of conditioned media on differentiation
      and invasiveness of trophoblast stem cells.
AB  - Embryo implantation in the human and rodents relies on the trophoblast's ability
      to invade into the uterine stroma, partly depending on proteinases degrading
      components of basement membrane and underlying extracellular matrix (ECM). We
      have utilized mouse trophoblast stem (TS) cells (Science, 1998, 282:2072) to
      study trophoblast invasion and trophoblast-ECM interactions in vitro. On plastic
      in fibroblast-conditioned medium containing fibroblast growth factor (FGF)-4 and
      heparin, the cells remain proliferative but display increased differentiation in
      media without these components. Marker gene expression (Eomes, Pl-1, Tpbp) and
      invasion assays showed that TS cells exhibit increased invasive capacity when
      differentiating into giant cells and spongiotrophoblasts in unconditioned media
      without FGF-4 and heparin. Concomitantly, an up-regulation of matrix
      metalloproteinases (MMP)-9 and -14 was observed. Culture on gels of the basement
      membrane-like Matrigel resulted in striking changes in morphology and gene
      expression. Differentiating TS cells invaded into this ECM in a three-dimensional
      culture, while in turn ECM contact enhanced differentiation of TS cells and up
      regulated the expression of MMP-9 and its tissue inhibitor (TIMP)-3. These
      findings implicate that the TS cell culture system used in this study can be
      utilized as a model for studying the regulation of trophoblast-ECM interactions,
      differentiation, and invasion in vitro.

PMID- 16563501
TI  - A mechanism distinct from the L-type Ca current or Na-Ca exchange contributes to
      Ca entry in rat ventricular myocytes.
AB  - The aim of this paper was to characterize the pathways that allow Ca(2+) ions to
      enter the cell at rest. Under control conditions depolarization produced an
      increase of intracellular Ca concentration ([Ca(2+)](i)) that increased with
      depolarization up to about 0 mV and then declined. During prolonged
      depolarization the increase of [Ca(2+)](i) decayed. This increase of [Ca(2+)](i)
      was inhibited by nifedipine and the calculated rate of entry of Ca increased on
      depolarization and then declined with a similar time course to the inactivation
      of the L-type Ca current. We conclude that this component of change of
      [Ca(2+)](i) is due to the L-type Ca current. If intracellular Na was elevated
      then only part of the change of [Ca(2+)](i) was inhibited by nifedipine. The
      nifedipine-insensitive component increased monotonically with depolarization and
      showed no relaxation on prolonged depolarization. This component appears to
      result from Na-Ca exchange (NCX). When the L-type current and NCX were both
      inhibited (nifedipine and Na-free solution) then depolarization decreased and
      hyperpolarization increased [Ca(2+)](i). These changes of [Ca(2+)](i) were
      unaffected by modifiers of B-type Ca channels such as chlorpromazine and AlF(3)
      but were abolished by gadolinium ions. We conclude that, in addition to L-type Ca
      channels and NCX, there is another pathway for entry of Ca(2+) into the
      ventricular myocyte but this is distinct from the previously reported B-type
      channel.

PMID- 16563502
TI  - Neurotensin enhances nitric oxide generation via the JAK2-STAT1 pathway in murine
      macrophage Raw264.7 cells during costimulation with LPS and IFNgamma.
AB  - Neurotensin has been known to be implicated in immune function, but its molecular
      mechanisms remain largely unclear. In this study, we report that neurotensin
      increased the intracellular calcium levels of murine macrophage Raw264.7 cells,
      and that this calcium increase disappeared in the presence of either U73122, a
      PLC inhibitor, or SR48692, a neurotensin receptor antagonist. Also, the
      production of nitric oxide (NO) during costimulation with lipopolysaccharide
      (LPS) and interferon gamma (IFNgamma) was potentiated by exposure to neurotensin,
      whereas neurotensin itself had no ability to induce NO generation. The up
      regulation of NO generation was correlated with the induction of inducible NO
      synthase (iNOS). In addition, the activities of janus activated kinase 2 (JAK2)
      signal transducer and activated transcription 1 (STAT1) and the migration
      capacity of macrophage were increased as the result of costimulation of
      neurotensin with LPS and IFNgamma, and pretreatment of either U73122 or SR48692
      attenuated these phenomenon. Moreover, the neurotensin-mediated enhancement of NO
      generation and migration were observed in the wild-type JAK2 transfected cells,
      but not in the dominant negative JAK2 transfected cells. Together, these results
      demonstrate that neurotensin can effect enhancement in LPS/IFNgamma-induced NO
      generation and migration capacity, via the JAK2-STAT1 pathway.

PMID- 16563503
TI  - Mantle cell lymphoma-derived cell lines: unique research tools.

PMID- 16563504
TI  - JAK2(V617F) and leukemic transformation in myelofibrosis with myeloid metaplasia.
AB  - Amongst 42 consecutive patients with leukemic transformation (LT) from
      myelofibrosis with myeloid metaplasia (MMM) 72% carried the JAK2(V617F) mutation.
      The mutation was observed at expected frequencies in all subtypes of MMM and
      acute myeloid leukemia. Although the patients with the mutation were younger and
      had a shorter interval to LT there was no difference in survival. Additionally,
      both the lack of mutation status progression in serial analysis (available in
      nine patients) and the low frequency of patients with high mutated allele burden
      suggest that LT arising from MMM is probably not dependent on changes in
      JAK2(V617F) mutation status.

PMID- 16563505
TI  - Molecular cloning and stress-induced expression of paralichthys olivaceus heme
      regulated initiation factor 2alpha kinase.
AB  - The heme-regulated initiation factor 2alpha kinase (HRI) is acknowledged to play
      an important role in translational shutoff in reticulocytes in response to
      various cellular stresses. In this study, we report its homologous cDNA cloning
      and characterization from cultured flounder embryonic cells (FEC) after treatment
      with UV-inactivated grass carp haemorrhagic virus (GCHV). The full-length cDNA of
      Paralichthys olivaceus HRI homologue (PoHRI) has 2391 bp and encodes a protein of
      651 amino acids. The putative PoHRI protein exhibits high identity with all
      members of eIF2alpha kinase family. It contains 12 catalytic subdomains located
      within the C-terminus of all Ser/Thr protein kinases, a unique kinase insertion
      of 136 amino acids between subdomains IV and V, and a relatively conserved N
      terminal domain (NTD). Upon heat shock, virus infection or Poly I:C treatment,
      PoHRI mRNA and protein are significantly upregulated in FEC cells but show
      different expression patterns in response to different stresses. In healthy
      flounders, PoHRI displays a wide tissue distribution at both the mRNA and protein
      levels. These results indicate that PoHRI is a ubiquitous eIF2alpha kinase and
      might play an important role in translational control over nonheme producing FEC
      cells under different stresses.

PMID- 16563506
TI  - Violence against women associated with arrests for sex trade but not drug
      charges.
AB  - The current study was designed to examine associations between gender-based
      violence and arrests due to sex trade or drug-related charges among a statewide
      sample of incarcerated women in Rhode Island. Incarcerated women were asked to
      participate in brief pre- and posttest surveys of their experiences of violence,
      sexual risk and substance use behaviors, as part of a study on the effectiveness
      of a family planning program in a state correctional facility; data from pretest
      surveys (N=447) were used for current analyses. Logistic regression analyses
      adjusted for demographics were used to assess significant associations between
      gender-based violence variables (i.e., adolescent intimate partner violence
      (IPV), adult IPV, childhood sexual assault (SA), adolescent SA, and adult SA) and
      arrests due to sex trade or drug-related charges. Significant relationships were
      observed between arrests for sex trade and adult SA (OR=2.1, 95%CI=1.2-3.6),
      adolescent IPV (OR=2.5, 95%CI=1.5-4.1), and adult IPV (OR=1.7, 95%CI=1.1-2.6); no
      significant associations were observed for drug-related charges. Findings from
      the current study demonstrate that experiences of gender-based violence are
      associated with arrests for sex trade but not drug-related charges. Interventions
      for incarcerated women are needed to consider and address history of
      victimization from gender-based violence and its relation to women's historic and
      future sex trade involvement.

PMID- 16563507
TI  - Unique responses of the avian macrophage to different species of Eimeria.
AB  - Coccidiosis is recognized as the major parasitic disease of poultry and is caused
      by the apicomplexan protozoa Eimeria. Increasing evidence shows the complexity of
      the host immune response to Eimeria and microarray technology presents a powerful
      tool for the study of such an intricate biological process. Using an avian
      macrophage microarray containing 4906 unique gene elements, we identified
      important host genes whose expression changed following infection of macrophages
      with sporozoites of Eimeria tenella (ET), Eimeria acervulina (EA), and Eimeria
      maxima (EM). This approach enabled us to identify a common core of 25 genetic
      elements whose transcriptional expression is induced or repressed by exposure to
      Eimeria sporozoites and to identify additional transcription patterns unique to
      each individual Eimeria species. Besides inducing the expression of IL-1beta, IL
      6, and IL-18 and repressing the expression of IL-16, Eimeria treated macrophages
      were commonly found to induce the expression of the CCL chemokine family members
      macrophage inflammatory protein (MIP)-1beta (CCLi1), K203 (CCLi3), and ah221
      (CCLi7). However, the CXCL chemokine K60 (CXCLi1) was found to be induced by
      macrophage exposure to E. tenella but was repressed upon macrophage exposure to
      E. maxima and E. acervulina. Fundamental analysis of avian chemokine and cytokine
      expression patterns offers insight into the unique avian immunological responses
      to these related but biologically unique pathogens.

PMID- 16563508
TI  - Computer prediction of allergen proteins from sequence-derived protein structural
      and physicochemical properties.
AB  - BACKGROUND: Computational methods have been developed for predicting allergen
      proteins from sequence segments that show identity, homology, or motif match to a
      known allergen. These methods achieve good prediction accuracies, but are less
      effective for novel proteins with no similarity to any known allergen. METHODS:
      This work tests the feasibility of using a statistical learning method, support
      vector machines, as such a method. The prediction system is trained and tested by
      using 1005 allergen proteins from the Allergome database and 22,469 non-allergen
      proteins from 7871 Pfam families. RESULTS: Testing results by an independent set
      of 229 allergen and 6717 non-allergen proteins from 7871 Pfam families show that
      93.0% and 99.9% of these are correctly predicted, which are comparable to the
      best results of other methods. Of the 18 novel allergen proteins non-homologous
      to any other proteins in the Swissprot database, 88.9% is correctly predicted. A
      further screening of 168,128 proteins in the Swissprot database finds that 2.9%
      of the proteins are predicted as allergen proteins, which is consistent with the
      estimated numbers from motif-based methods. CONCLUSIONS: Our study suggests that
      SVM is a potentially useful method for predicting allergen proteins and it has
      certain capability for predicting novel allergen proteins. Our software can be
      accessed at .

PMID- 16563509
TI  - New insights on macrophage migration inhibitory factor: based on molecular and
      functional analysis of its homologue of Chinese amphioxus.
AB  - Macrophage migration inhibitory factor (MIF) is an intricate cytokine. Many
      questions about it are not fully resolved. In order to identify the role of MIF
      in Chinese amphioxus, its genomic organization, transcription pattern and
      enzymatic activity were studied. It's found that MIF has multi-copy gene number
      in the Chinese amphioxus genome and special transcription pattern in reproductive
      organs. Interestingly, the recombinant Bbt-MIF has tantomerase and redox
      activity, but fails to utilize GSH to reduce insulin instead of DTT, strikingly
      different from MIF in mammalian. All these results indicate that MIF gene must
      have undergone important changes in structure and function during the transition
      of invertebrate/vertebrate and might exert important role in this primitive
      species, which may be quite different from those found in vertebrate.

PMID- 16563510
TI  - Cloning, sequence analysis and confirmation of derived gene sequences for three
      epitope-mapped monoclonal antibodies against human phagocyte flavocytochrome b.
AB  - The integral membrane protein flavocytochrome b (Cyt b) is the catalytic core of
      the NADPH oxidase complex, a multicomponent enzyme system that initiates a
      cascade of reactive oxygen species that play a critical role in innate immunity
      and vascular physiology. Epitope-mapped, monoclonal antibodies (mAb) that
      recognize the large (gp91phox) and small (p22phox) subunits of Cyt b provide
      valuable reagents that have been used to examine structural and mechanistic
      aspects of oxidase function. In the present study, the heavy and light chain
      variable region genes of the Cyt b-specific mAbs 44.1, NS5, and NL7 have been
      amplified by RT-PCR, cloned and subject to DNA sequence analysis. Since the 5'
      degenerate primer sets used for mAb gene amplification were observed to introduce
      extensive heterogeneity into the heavy and light chain FR1 regions, N-terminal
      protein sequence analysis was also conducted to obtain the correct amino acid
      sequence of this region. In order to confirm the identity of the cloned genes,
      intact mAbs were resolved by two-dimensional electrophoresis and subject to in
      gel tryptic digestion for analysis by both MALDI and nanospray LC-MS/MS.
      Databases searches using the derived mAb sequences predicted residues comprising
      CDR loops, identified candidate germline genes, and showed the respective
      germline genes to accurately predict the N-terminal amino acid residues for each
      variable region. The above studies report the amino acid sequence of Cyt b
      specific mAb variable region genes with high confidence and provide essential
      information for future efforts at Cyt b structure analysis by resonance energy
      transfer and X-ray crystallography.

PMID- 16563511
TI  - Weakly coupled transition-metal centres: high-level calculations on a model
      Fe(IV)-Fe(IV) system.
AB  - We briefly review different approaches to calculating the Heisenberg exchange
      coupling between two weakly coupled metal centres in a complex, with particular
      emphasis on using multiconfigurational methods to treat individually all the
      states that arise, without the use of symmetry breaking to obtain a mixed state
      in which the spins are coupled antiferromagnetically. We illustrate the
      multiconfigurational approach first using very accurate calculations on two
      weakly interacting high-spin nitrogen atoms, and then we use these very accurate
      results to calibrate broken-symmetry single configuration approaches, including
      density-functional theory with various different functionals. We then consider a
      dinuclear iron complex chosen to reproduce qualitatively the environment around
      the diiron-dioxygen "diamond core" in soluble methane monooxygenase hydroxylase.
      Agreement between high-level multiconfigurational methods and broken-symmetry
      density-functional theory is only fair.

PMID- 16563512
TI  - New unsymmetric dinuclear Cu(II)Cu(II) complexes and their relevance to
      copper(II) containing metalloenzymes and DNA cleavage.
AB  - The new homodinuclear complexes, [Cu(2)(II)(HLdtb)(mu-OCH(3))](ClO(4))(2) (1) and
      [Cu(2)(II)(Ldtb)(mu-OCH(3))](BPh(4)) (2), with the unsymmetrical N(5)O(2) donor
      ligand (H(2)Ldtb) - {2-[N,N-Bis(2-pyridylmethyl)aminomethyl]-6-[N',N'-(3,5-di
      tert-butylbenzyl-2-hydroxy)(2-pyridylmethyl)]aminomethyl}-4-methylphenol have
      been synthesized and characterized in the solid state by X-ray crystallography.
      In both cases the structure reveals that the complexes have a common {Cu(II)(mu
      phenoxo)(mu-OCH(3))Cu(II)} structural unit. Magnetic susceptibility studies of 1
      and 2 reveal J values of -38.3 cm(-1) and -2.02 cm(-1), respectively, and that
      the degree of antiferromagnetic coupling is strongly dependent on the
      coordination geometries of the copper centers within the dinuclear {Cu(II)(mu
      OCH(3))(mu-phenolate)Cu(II)} structural unit. Solution studies in
      dichloromethane, using UV-Visible spectroscopy and electrochemistry, indicate
      that under these experimental conditions the first coordination spheres of the
      Cu(II) centers are maintained as observed in the solid state structures, and that
      both forms can be brought into equilibrium ([Cu(2)(HLdtb)(mu
      OCH(3))](2+)=[Cu(2)(Ldtb)(mu-OCH(3))](+)+H(+)) by adjusting the pH with Et(3)N
      (Ldtb(2-) is the deprotonated form of the ligand). On the other hand,
      potentiometric titration studies of 1 in an ethanol/water mixture (70:30 V/V;
      I=0.1M KCl) show three titrable protons, indicating the dissociation of the
      bridging CH(3)O(-) group.The catecholase activity of 1 and 2 in methanol/water
      buffer (30:1 V/V) demonstrates that the deprotonated form is the active species
      in the oxidation of 3,5-di-tert-butylcatechol and that the reaction follows
      Michaelis-Menten behavior with k(cat)=5.33 x 10(-3)s(-1) and K(M)=3.96 x 10(-3)M.
      Interestingly, 2 can be electrochemically oxidized with E(1/2)=0.27 V vs.Fc(+)/Fc
      (Fc(+)/Fc is the redox pair ferrocinium/ferrocene), a redox potential which is
      believed to be related to the formation of a phenoxyl radical. Since these
      complexes are redox active species, we analyzed their activity toward the nucleic
      acid DNA, a macromolecule prone to oxidative damage. Interestingly these
      complexes promoted DNA cleavage following an oxygen dependent pathway.

PMID- 16563513
TI  - Enhancement of antibacterial activity of beta-lactam antibiotics by [P2W18O62]6-,
      [SiMo12O40]4-, and [PTi2W10O40]7- against methicillin-resistant and vancomycin
      resistant Staphylococcus aureus.
AB  - The enhancement of antibacterial activity of beta-lactam antibiotics by
      polyoxometalates against methicillin-resistant Staphylococcus aureus (MRSA) and
      vancomycin-resistant S. aureus (VRSA) was investigated by using K6[P2W18O62] .
      14H2O (P2W18), K4[SiMo12O40] . 3H2O (SiMo12), and K7[PTi2W10O40] . 6H2O
      (PTi2W10). Susceptibility test by a beta-lactam-disk method showed the
      synergistic effect of the polyoxometalates in combination with oxacillin against
      both MRSA and VRSA. Energy dispersive X-ray analysis of the strain treated with
      P2W18 revealed localization of the polyoxometalate-tungsten atoms at the
      periphery of the cell, and the biological reduction of P2W18 and SiMo12 proceeded
      within both cells of MRSA and VRSA as far as they keep alive. These results
      indicate that the polyoxometalates can penetrate through the cell wall consisting
      of peptidoglycan layers and reach cytoplasmic membrane. The inhibitory effect of
      the polyoxometalates on both mecA- and pbp-induced mRNA expression of both MRSA
      and VRSA cells, verified by the RT-PCR-electrophoresis analysis, is observed, and
      the mechanism of the synergistic effect by the polyoxometalates is discussed in
      terms of the depression of penicillin-binding protein 2' (PBP2') coded by mecA
      gene.

PMID- 16563514
TI  - Screening and optimization of the derivatization of polar herbicides with
      trimethylanilinium hydroxide for GC-MS analysis.
AB  - In the present study, a derivatization method for the determination of acidic
      herbicides has been investigated. This procedure involves the methylation with
      the quaternary ammonium salt trimethylanilinium hydroxide (TMAH) directly in the
      gas chromatographic auto-sampler vial for analysis by gas chromatography combined
      with mass spectrometry. The derivatization reaction has been screened for
      influential factors and statistically significant parameters. The identified
      factors, reaction time, temperature and hold-up time were optimized by a complete
      factorial response surface design and optimal reaction conditions were generated.
      Finally, the optimized methylation procedure was compared to different alkylation
      methods and obtained results demonstrated the applicability of derivatization
      with trimethylanilinium hydroxide. Acidic herbicides used in the study consist of
      several families of compounds like derivatives of acetic acid (2,4-D and 2,4,5
      T), butanoic acid (MCPB), benzoic acid (chloramben, dicamba), phenol (dinoseb and
      dinoterb), propanoic acid (mecoprop) and other miscellaneous acids such as
      pyridinecarboxlyic acid (picloram). A reliably working, rapid method for the
      preparation of methyl compounds is generated with respect to automation for
      routine analysis.

PMID- 16563515
TI  - Analysis of amino acids and carbohydrates in green coffee.
AB  - The analysis of carbohydrates and amino acids in green coffee is of the utmost
      importance since these two classes of compounds act as precursors of the Maillard
      reaction during which the colour and aroma are formed. During the course of the
      Maillard reaction potentially harmful substances like acrylamide or 5
      hydroxymethyl-furfural accrue as well. The carbohydrates were analysed by anion
      exchange chromatography with pulsed amperometric detection and the amino acids by
      reversed phase chromatography after derivatization with 6-amino-quinolyl-N
      hydroxysuccinimidyl carbamate and fluorescence detection. Both methods had to be
      optimized to obtain a sufficient resolution of the analytes for identification
      and quantification. Sucrose is the dominant carbohydrate in green coffee with a
      concentration of up to 90 mg/g (mean = 73 mg/g) in arabica beans and
      significantly lower amounts in robusta beans (mean=45 mg/g). Alanine is the amino
      acid with the highest concentration (mean = 1200 microg/g) followed by asparagine
      (mean = 680 microg/g) in robusta and 800 microg/g and 360 microg/g in arabica
      respectively. In general, the concentration of amino acids is higher in robusta
      than in arabica.

PMID- 16563516
TI  - Separation of 1,4-benzodiazepines by micellar elektrokinetic capillary
      chromatography.
AB  - In this work the applicability of micellar elektrokinetic capillary
      chromatography (MECC) for the determination of benzodiazepines (BZD) has been
      studied. The applied method was used for the simultaneous separation of 8 BZDs
      (alprazolam, bromazepam, chlordiazepoxide, diazepam, flunitrazepam, medazepam,
      oxazepam, nitrazepam), and also for the study of stability in acidic medium. A
      fast and reliable method has been developed; using a separation buffer composed
      of sodium tetraborate 25 mM (pH 9.5), SDS (50 mM) and methanol (at least 12%) as
      an organic modifier.

PMID- 16563517
TI  - Detecting time-dependent coherence between non-stationary electrophysiological
      signals--a combined statistical and time-frequency approach.
AB  - Various time-frequency methods have been used to study time-varying properties of
      non-stationary neurophysiological signals. In the present study, a time-frequency
      coherence estimate using continuous wavelet transform (CWT) together with its
      confidence intervals are proposed to evaluate the correlation between two non
      stationary processes. The approach is based on averaging over repeat trials. A
      systematic comparison between approaches using CWT and short-time Fourier
      transform (STFT) is carried out. Simulated data are generated to test the
      performance of these methods when estimating time-frequency based coherence. In
      contrast to some recent studies, we find that CWT based coherence estimates do
      not supersede STFT based estimates. We suggest that a combination of STFT and CWT
      would be most suitable for analysing non-stationary neural data. Tests are
      presented to investigate the time and frequency discrimination capabilities of
      the two approaches. The methods are applied to two experimental data sets:
      electroencephalogram (EEG) and surface electromyogram (EMG) during wrist
      movements in a healthy subject, and local field potential (LFP) and surface EMG
      recordings during resting tremor in a Parkinsonian patient. Supporting software
      is available at and .

PMID- 16563518
TI  - Rapid assay for quantitative measurement of apoptosis in cultured cells and brain
      tissue.
AB  - Analysis of apoptosis in brain tissue following ischemia, hypoxia, or oxidative
      stress has technical limitations. The use of counting cells displaying apoptotic
      morphology is time intensive, vulnerable to sampling errors, and suffers from low
      numbers of total recorded events. Other cell death assays such as agarose gel
      analysis of DNA fragmentation, TUNEL, or ELISA are time intensive, limited to a
      single endpoint measure, and can be technically difficult to perform or
      reproduce. To overcome these limitations, we set out to develop a technique using
      flow cytometry to measure apoptosis based on the physical properties of light
      scatter produced from isolated nuclei. This dye/marker free approach would bypass
      many of the inherent encumbrances and reproducibility problems found in other
      apoptosis assays. Here we demonstrate that this new technique, using flow
      cytometry performed on isolated nuclei, allows rapid quantitation of apoptosis in
      a variety of brain tissues without the need for intercalating dyes or fluorescent
      markers. We conclude that this technique significantly improves currently
      available protocols to quantify apoptosis from tissue and offers the possibility
      to perform additional analysis on the same population of nuclei via downstream
      assays.

PMID- 16563519
TI  - Early predictors of deliberate self-harm among adolescents. A prospective follow
      up study from age 3 to age 15.
AB  - BACKGROUND: To study predictors at age 3 and at age 12 for ideations and acts of
      deliberate self-harm at age 15 in a representative birth cohort. METHOD:
      Information about ideations and acts of deliberate self-harm at age 12 and at age
      15 was obtained from parents and children. Information about the child's problems
      was obtained at age 3 using the Child Behavior Checklist 2/3 (CBCL 2/3), and at
      age 12 with the CBCL and Youth Self-report (YSR). Furthermore, when the child was
      12, mothers and fathers gave information about their own health, well-being and
      mental distress, and about family functioning measured with the Family Assessment
      Device (FAD). RESULTS: There was a significant increase in self-reported
      deliberate self-harm (ideations or acts) from age 12 to age 15, especially among
      girls (from 3% to 13%). Parent-child agreement on acts and ideations of
      deliberate self-harm was very low at both time-points (proportion of agreement
      0.0-0.2). Self-reports of deliberate self-harm at age 12 independently predicted
      both acts and ideations of deliberate self-harm at age 15. Female gender, self
      reports of internalizing problems and somatic complaints, parent reports of
      child's externalizing problems and aggressivity, mother's reports of her health
      problems, and living in nonintact family at age 12 independently predicted self
      reported acts of deliberate self-harm 3 years later. Parent reports of child's
      learning difficulties, and self-reports of being bullied independently predicted
      ideations of deliberate self-harm at age 15. Parent reports of child's
      psychopathology at age 3 assessed with the CBCL 2/3 had no predictive association
      with ideation or acts of deliberate self-harm at age 15. CONCLUSIONS: Acts of
      deliberate self-harm in mid-adolescence are due to an accumulation of earlier
      family and parental distress, and child's externalizing and internalizing
      problems. Information about deliberate self-harm at age 12 is an important
      warning sign of deliberate self-harm in mid-adolescence.

PMID- 16563520
TI  - Current and former depression and their relationship to the effects of social
      comparison processes. Results of an internet based study.
AB  - BACKGROUND: According to cognitive vulnerability stress models of depression,
      negative cognitions are supposed to be stable characteristics of depressed
      individuals even between depressive episodes. Depressed people also interpret
      social information more negatively than healthy people, perhaps even between
      depressive episodes. Frequency of social comparison processes is correlated with
      low self-esteem and uncertainty, which is common in depression. QUESTIONS: Do
      people with lifetime depressive episodes engage in social comparisons more often
      and do they react more negatively to an upward comparison than normal controls?
      And if they do, is this just due to current depressive symptoms? METHOD: A
      questionnaire including the BDI II was administered as an internet link to all
      students or employees of a large University. 913 participants responded. After
      assessing social comparison orientation we used an upward comparison paradigm by
      asking the participants to compare themselves with a better-off person on several
      dimensions. Finally lifetime and current depressive symptoms were assessed.
      RESULTS: Depressed persons engage in social comparison processes more often than
      normal controls. Positive affect decreased in the whole sample as a reaction of
      to social comparison. This effect was stronger among persons with at least one
      depressive episode in the past, and this was not just due to current depression.
      CONCLUSION: Depressed persons engage more often in social comparison processes
      and they additionally react more negatively to upward comparisons than healthy
      controls. The result that even those not currently depressed with lifetime
      depressive episodes show a similar negative reaction to an upward comparison
      indicates that social comparisons are situations that interact with a stable
      cognitive vulnerability leading to negative affect and stronger negative
      reactions.

PMID- 16563521
TI  - Clinical relevance of depressive symptom improvement in bipolar I depressed
      patients.
AB  - BACKGROUND: Gaps remain between rating scale changes obtained in a clinical trial
      and what those results mean in clinical practice. OBJECTIVE: To better understand
      the relevance of results from a clinical trial we examined the relationship
      between rating scale measures and the clinicians' assessment of illness severity.
      METHODS: Data from a randomized double-blind 8-week study of bipolar I depression
      were examined post hoc in patients who received placebo (PLA, n = 355),
      olanzapine (n = 351) (OLZ, 5 to 20 mg/d), or olanzapine-fluoxetine combination (n
      = 82) (OFC, 6 and 25, 6 and 50, or 12 and 50 mg/d). Principal components analysis
      identified related symptoms (factors) from Montgomery-Asberg Depression Rating
      Scale (MADRS) item scores. Regression analysis examined baseline to endpoint
      changes in factor scores and Clinical Global Impression (CGI) scores. Mixed
      effects model repeated measures analysis assessed differences between treatment
      groups. RESULTS: MADRS factors identified were: sadness, negative thoughts,
      detachment, and neurovegetative symptoms. Factor and CGI scores were
      significantly reduced from baseline to endpoint (LOCF) in the combination therapy
      group as compared with placebo (p < .01). Changes in factor scores were highly
      correlated (p < .001) with changes in the CGI. Over 80% of this treatment effect
      was attributable to indirect effects of improvements in the MADRS factors, the
      remaining difference could not be explained even when changes in the YMRS and
      HAMA scores were included in the analytical model. CONCLUSIONS: The changes in
      MADRS factors were closely aligned with the clinician's assessment of overall
      depression severity, which may suggest a high degree of clinical relevance for
      differences observed between treatments.

PMID- 16563522
TI  - Identification of differences in gene expression in primary cell cultures of
      human endometrial epithelial cells and trophoblast cells following their
      interaction.
AB  - BACKGROUND: The interaction between epithelial cells of endometrium and
      trophoblast cells during implantation is presumed to be accompanied by a change
      in gene expression in the cell types involved. The objective of this study was to
      identify such differentially expressed genes. METHODS: The interaction between
      the cell types was simulated in vitro by growing primary cell cultures of human
      endometrial epithelial cells and trophoblast cells together (co-culture) and
      separately (control cultures). Gene expression in the cell cultures was compared
      using the Differential Display method and confirmed using a modified Northern
      Blot method. RESULTS: Twelve transcripts were identified as being differentially
      expressed following the interaction between trophoblast and endometrial cells.
      Some of these sequences show homology to known human genes while other sequences
      are coding for potential novel genes: (1) one sequence was homologous to the to
      Homer 1 gene, (2) one identical to the mRNA for XP-G factor, (3) one similar to a
      hypothetical protein, (4) transcripts showing homologies to a mRNA coding for a
      cellular proapoptotic protein, and (5) sequences homologous to regions on human
      chromosomes 5 and 16. Besides, some differentially expressed transcripts have
      sequences, which could be translated into ribosomal proteins or possibly code for
      novel proteins. CONCLUSION: These sequences may be important to the course of
      events following the interaction between endometrial epithelial and trophoblast
      cells and responsible for implantation.

PMID- 16563523
TI  - Receptor-mediated transport of LIF across blood-spinal cord barrier is
      upregulated after spinal cord injury.
AB  - Leukemia inhibitory factor (LIF) crosses the normal blood-brain and blood-spinal
      cord barrier (BBB) by a saturable transport system [Pan, W., Kastin, A.J.,
      Brennan, J.M., 2000. Saturable entry of leukemia inhibitory factor from blood to
      the central nervous system. J. Neuroimmunol. 106, 172-180]. Since LIF is a
      cytokine beneficial to spinal cord regeneration, understanding the regulation of
      its transport across the injured BBB may help in the design of strategies for the
      treatment of spinal cord injury (SCI). In this study, we initially showed that
      transport of LIF is mediated by its specific receptor LIFRalpha (gp190), using
      both adult mice and monolayers of mouse brain microvessel endothelial cells.
      Permeation of radioactively labeled LIF was inhibited not only by excess
      unlabeled LIF, but also by a blocking antibody to the extracellular domain of
      gp190 LIFRalpha receptor. This showed that the saturable transport of LIF across
      the BBB involves LIFRalpha. We then tested the hypothesis that this transport
      system can be upregulated after SCI. SCI was generated by an established
      compression method at the upper lumbar level. Transport was studied 1 week after
      SCI, a time of tissue repair following ischemia and inflammation. Spinal cord
      uptake of 99mTc-albumin 10 min after intravenous injection was used as an
      indicator of paracellular permeability of the BBB, its small but significant
      increase at the injury site indicating the level of persistent BBB disruption.
      The uptake of 125I-LIF by the injured lumbar spinal cord was significantly
      greater than that in the uninjured controls as well as that of 99mTc-albumin.
      Both excess unlabeled LIF and the blocking antibody against LIFRalpha
      significantly suppressed the increased entry of 125I-LIF without affecting that
      of 99mTc-albumin. Thus, the increased blood-to-spinal cord permeation of LIF was
      not solely explained by barrier disruption but involved LIFRalpha. This enhanced
      transport correlated with increased expression of LIFRalpha shown by
      immunofluorescent staining and Western blot. Therefore, LIFR at the BBB provides
      an important target for therapeutic intervention.

PMID- 16563524
TI  - Immunohistochemical screening for autoantibodies against lateral hypothalamic
      neurons in human narcolepsy.
AB  - Most human patients with narcolepsy have no detectable hypocretin-1 in their
      cerebrospinal fluid. The cause of this hypocretin deficiency is unknown, but the
      prevailing hypothesis states that an autoimmune-mediated mechanism is
      responsible. We screened for the presence of autoantibodies against neurons in
      the lateral hypothalamus in 76 patients and 63 controls, using
      immunohistochemistry. Autoantibodies were present in two patients, but also in
      two controls. However, one of the patients had a clearly different staining
      pattern and nerve endings of immunolabeled cells were found to project onto
      hypocretin-producing neurons, suggesting a possible pathophysiological role.
      Humoral immune mechanisms appear not to play a role in the pathogenesis of
      narcolepsy, at least not in the clinically overt stage of the disease.

PMID- 16563525
TI  - A membrane-based quantitative carrier test to assess the virucidal activity of
      disinfectants and persistence of viruses on porous fomites.
AB  - A membrane-based quantitative carrier test method to assess the virucidal
      activity of disinfectants and the persistence of viruses on fomites under
      different environmental conditions is described. The method is based on the
      inactivation of the virus adsorbed to cellulose ester membranes followed by the
      direct enumeration of the viruses surviving the treatment without the need of an
      elution step. The method was suitable for four different human enteroviruses
      tested. Experiments comparing the infectivity loss of human enteroviruses in
      suspension or adsorbed to the filters after treatment with chlorine and
      glutaraldehyde showed that the human enteroviruses tested suffered significantly
      greater log10 reductions when suspended than when adsorbed. Significant
      differences in the effect of the disinfectants on the various human enteroviruses
      tested were also observed. Moreover, the procedure allowed determining the
      inactivation of viruses on fomites under different environmental conditions. Low
      temperatures and high relative humidities favored the survival of human
      enteroviruses. Also, viruses adsorbed to the membranes retained their infectivity
      frozen at -70 degrees C for more than 1 year, thus providing the possibility of
      preparing very simple reference materials for testing virucidal activities of
      antiseptics and disinfectants.

PMID- 16563526
TI  - Development and evaluation of a real-time RT-PCR assay for quantification of cell
      free human immunodeficiency virus type 2 using a Brome Mosaic Virus internal
      control.
AB  - Quantification of cell-free virus in plasma is important for monitoring disease
      progression and for assessing the response to antiretroviral therapy in both
      human immunodeficiency type 1 and type 2 (HIV-1, HIV-2) infections. Although
      commercial assays suitable for HIV-1 quantification have been used for more than
      a decade, no commercial assays are yet available for the measurement of cell-free
      HIV-2. We have therefore developed a novel real-time RT-PCR assay which, unlike
      previously described 'in house' assays, incorporates a Brome Mosaic Virus (BMV)
      internal control to minimise the risk of generating false-negative or falsely low
      results due to unrecognised problems with viral RNA purification, cDNA synthesis
      or PCR amplification. The assay has a dynamic range of >5 log10, detects the
      clinically important HIV-2 subtypes A and B with high sensitivity and shows no
      cross reactivity with HIV-1. The 95% detection limit is approximately 100 HIV-2
      RNA copies/ml and both the inter-assay and intra-assay variability are low (CV%
      at 1.8 x 10(5) copies/ml, 13.3% and 5.7%, respectively). Overall, plasma HIV-2
      RNA was detected in 38% of 167 unselected HIV-2 antibody-positive samples
      analysed over a 2 year period. The assay described provides an ideal system for
      studying viral replication in HIV-2 infected patients and for monitoring
      antiretroviral therapy.

PMID- 16563527
TI  - A mass spectrometry-based proteomic approach to study Marek's Disease Virus gene
      expression.
AB  - Marek's Disease Virus (MDV) is an avian herpesvirus that causes a
      lymphoproliferative disorder in chickens. MDV transitions between a lytic phase
      in which new viruses are produced and a latent phase in which the virus lays
      dormant. The mechanism controlling this lytic-to-latent switch remains unclear.
      To better understand the lytic phase of MDV infection, a mass spectrometry-based
      strategy was developed to identify viral proteins and to qualitatively examine
      their abundance in lytically infected chicken embryo fibroblast (CEF) cells. A
      combination of strong cation exchange chromatography (SCXC) and microcapillary
      reversed-phase liquid chromatography-tandem mass spectrometry (murpLC/MS/MS) was
      used to resolve peptides from tryptic digests of MDV-infected CEF cell lysates.
      Peptides were identified by searching the tandem mass spectra against a protein
      database containing both MDV proteins and all currently available Gallus gallus
      proteins using the SEQUEST algorithm. A total of 427 MDV peptides, corresponding
      to 82 unique proteins, were identified, with 56 of them detected with at least
      two unique peptides. Overall, nearly 80% of all putative MDV proteins expressed
      in infected CEF cells were identified. We anticipate that this approach will be a
      viable method for determining how viral and host proteome changes occurring in
      Marek's Disease pathogenesis regulate the switch between the lytic and latent
      phases of the MDV life cycle.

PMID- 16563528
TI  - Motion perception in rats (Rattus norvegicus sp.): deficits in albino Wistar rats
      compared to pigmented Long-Evans rats.
AB  - Motion perception was tested in pigmented Long-Evans and albino Wistar rats
      (Rattus norvegicus sp.) using moving random dot patterns. Pigmented as well as
      albino rats could distinguish a fully coherently moving pattern from dynamic
      noise. However, motion coherence thresholds were significantly lower in pigmented
      compared to albino rats (12% and 30% coherence, respectively). These results
      indicate that pigmented rats have well developed motion coherence perception,
      whereas albino rats are severely impaired but not motion blind.

PMID- 16563529
TI  - The clinical significance of electrophysiological measures of olfactory function.
AB  - AIM: To establish the detectability of olfactory event-related potentials (OERP)
      in relation to the results from psychophysical tests of olfactory function.
      METHODS: Fifty-nine men and 64 women (aged 19-89 years) participated all of whom
      presented themselves to a specialized "Smell and Taste Clinic" because of
      chemosensory complaints. Their olfactory function was assessed by means of
      psychophysical tests, e.g., assessment of odor threshold, odor discrimination,
      and odor identification, which were combined in a composite "Threshold
      Discrimination Identification" score ("TDI score"). OERP were obtained in
      response to the olfactory stimulant phenyl ethyl alcohol; their presence/absence
      was judged by a trained observer. Using logistic regression the TDI score was
      calculated in relation to the subjects' olfactory function at which the
      probability of the presence of OERP became greater than chance. RESULTS: Based on
      psychophysical tests, 40 subjects were diagnosed with functional anosmia, 40 with
      hyposmia, and 43 subjects scored within the normal range. Causes of hyposmia and
      anosmia included congenital anosmia, Parkinson's disease, head trauma, infections
      of the upper respiratory tract, and sinunasal disease. A TDI score of 22.6
      equivalent to "pronounced hyposmia" was identified as the turning point at which
      the probability of detection of OERP was higher than 50%. Its 95% confidence
      interval of 16.1-27.8 well reflected the range of hyposmia, i.e., was above
      significant loss of olfactory function (functional anosmia, TDI score<15.5) and
      below normal olfactory function (TDI score>30.5). CONCLUSION: The present results
      indicate that the probability to detect an OERP becomes greater than 50% within a
      range of olfactory function that separates functional anosmia from normosmia.
      Presence of OERP clearly signifies presence of olfactory function while this is
      not always the other way around with absence of OERP.

PMID- 16563530
TI  - Neurobehavioral profiles during the acute phase of ethanol withdrawal in
      adolescent and adult Sprague-Dawley rats.
AB  - RATIONALE: Adolescent and adult rats show differential sensitivity to many of the
      effects of ethanol. OBJECTIVES: The current studies were designed to further
      explore differences in the development of ethanol dependence by examining anxiety
      like behavior, acoustic startle, prepulse inhibition, and EEG activity during the
      acute phase of ethanol withdrawal. METHODS: Male Sprague-Dawley rats were exposed
      to ethanol vapor (12h/day for 14 days) during adolescence or adulthood.
      Neurobehavioral assessments were performed before exposure began and then during
      the acute phase of ethanol withdrawal (i.e., 7-10h after the termination of daily
      ethanol exposure). RESULTS: Behavior in the light-dark box did not reveal indices
      of pronounced anxiety-like behavior in ethanol exposed rats from either age group
      during withdrawal. Acoustic startle magnitude was significantly reduced and
      prepulse inhibition significantly enhanced in ethanol exposed rats during
      withdrawal, but these changes were independent of age. Frontal cortical EEG
      activity was not altered during ethanol withdrawal, but high frequency power in
      the parietal power EEG (i.e., 16-32 and 32-50 Hz) was selectively increased in
      ethanol exposed adolescents. CONCLUSIONS: The overall indices of ethanol
      withdrawal observed in these studies were mild, but these data do support the
      hypothesis that ethanol withdrawal symptoms can differentially develop in
      adolescent and adult rats. However, sensitivity to ethanol during adolescence can
      be increased or decreased depending on the symptom being assessed. As a result,
      it is unclear if more rapid development of ethanol dependence in adolescents is a
      factor, which facilitates the development of alcoholism.

PMID- 16563531
TI  - Apelin and its receptor are expressed in human osteoblasts.
AB  - OBJECTIVES: Apelin is a recently discovered peptide that is the endogenous ligand
      for the orphan G-protein-coupled receptor APJ. Adipocytes can express and secrete
      apelin. The aim of this study was to characterize apelin and APJ expression in
      human osteoblasts and to investigate the effects of apelin on osteoblasts.
      RESULTS: Apelin and APJ were expressed in human osteoblasts. Apelin stimulated
      proliferation of human osteoblasts, but had no effect on alkaline phosphatase
      (ALP) activity, osteocalcin and type I collagen production in human osteoblasts.
      Suppression of APJ with small-interfering RNA (siRNA) abolished the apelin
      induced cell proliferation. Apelin induced activation of Akt
      (Phosphatidylinositol-3 kinase downstream effector), but not MAPKs, such as c-jun
      N-terminal Kinase (JNK), p38 and ERK1/2 in human osteoblasts. This effect was
      blocked by suppression of APJ with siRNA. Furthermore, LY294002 (PI3 kinase
      inhibitor) blocked the activation of Akt by apelin and abolished the apelin
      induced cell proliferation. CONCLUSIONS: Human osteoblasts express apelin and APJ
      and apelin enhances human osteoblast proliferation, but has no effect on
      osteoblast differentiation, and APJ/PI3 kinase/Akt pathway is involved in the
      proliferation response. These findings suggest that apelin may function as a
      mitogenic agent for osteoblasts.

PMID- 16563532
TI  - Effect of Zn treatment on wild type and MT-null cell lines in relation to
      apoptotic and/or necrotic processes and on MT isoform gene expression.
AB  - It has been shown in various systems that zinc is able to antagonize the
      catalytic properties of the redox-active transition metals iron and copper,
      although the process is still unclear. Probably, the protective effect of Zn
      against oxidative stress is mainly due to the induction of a scavenger metal
      binding protein such as metallothionein (MT), rather than a direct action. To
      support this hypothesis, in this study, the effects of Zn, Cu, Fe, Zn + Cu and Zn
      + Fe treatments were investigated in a fibroblast cell line corresponding to an
      SV40-transformed MT-1/-2 mutant (MT-/-), and in wild type (MT+/+), by valuing
      metal concentrations and apoptotic and/or necrotic processes. We also
      investigated the synthesis of MT and the levels of both MT-1 and MT-2 mRNAs. In
      MT+/+ cells, co-treatment with Zn + Fe caused a decrease in Fe content compared
      to treatment with Fe alone. After Zn and Zn + Cu exposure the expression of MT-1
      and MT-2 isoforms increased with a concomitant increase in MT synthesis. Annexin
      V-FITC and propidium iodide staining revealed necrotic or apoptotic cells in
      terminal stages, especially after Fe treatments. Immunofluorescent staining with
      an anti-ssDNA Mab and annexin detected a lower signal in co-treated cells
      compared to the single treatments in both cell lines. The intensity and quantity
      of fluorescence resulting from anti-ssDNA and Annexin V staining of MT null cells
      was higher compared to wild type cells. These results suggest that Zn alone does
      not completely exert an anti-oxidant effect against Cu and Fe toxicity, but that
      induction of MT is necessary.

PMID- 16563533
TI  - Interdependence and distribution of subclinical mastitis and intramammary
      infection among udder quarters in dairy cattle.
AB  - The objective of the present study was to determine the distribution of
      subclincial mastitis and intramammary infection (IMI) across udder quarters and
      to quantify, if any, the level of interdependence between quarters. Subclinical
      mastitis was defined as an udder quarter somatic cell count of > or =250,000.
      Intramammary infection was defined as the presence of pathogens in an udder
      quarter. The data used in the analyses consisted 6577 test-day records from 2034
      lactations with observations on subclinical mastitis and 8428 test-day records
      from 2575 lactations with observations on IMI; each test-day record consisted
      data on all four udder quarters. Records were from animals on three research
      herds in southern Ireland. Observed distributions of IMI were compared to
      expected distributions, estimated using a binomial probability distribution,
      assuming independence among quarters. Generally, the observed frequencies
      deviated significantly from the expected frequencies, indicating some level of
      interdependence between quarters. Intraclass correlations were estimated from a
      mixed model including cow and test-day record nested within cow as random
      effects; fixed effects in the model included herd, year of calving, month of
      calving, parity, days in milk at sampling and interactions. Intraclass
      correlations within test-day record ranged from 0.14 to 0.50 for subclinical
      mastitis and from 0.02 to 0.40 for IMI. Thus, substantial interdependence between
      quarters exists which should be accounted for when analysing data from
      experiments across udder quarters. Failure to do so may result in incorrect
      inferences from statistical tests.

PMID- 16563534
TI  - Evaluation of a modified antimycobacterial susceptibility test using Middlebrook
      7H10 agar containing 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride.
AB  - A rapid and accurate antimycobacterial susceptibility test is essential for
      effective treatment of tuberculosis. The aim of this study was to evaluate a
      modified method applying 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC) to
      the Clinical and Laboratory Standards Institute (CLSI) guideline for
      susceptibility testing of Mycobacterium tuberculosis. A total of 132 clinical
      isolates of M. tuberculosis, forty-eight isolates showing resistance to one or
      more of the first-line antituberculosis drugs, and eighty-four fully susceptible
      isolates were collected from hospitals of a nationwide distribution from June to
      September 2004. The modified procedure was conducted basically according to the
      agar-proportion method described in the CLSI Guideline both with STC 50 mug/mL.
      The amount of growth in each well was recorded and graded at 2nd and 3rd weeks
      after inoculation. After 3 weeks of incubation, the diagnostic sensitivity and
      specificity for the detection of drug-resistant strains of STC-containing agar
      proportion methods were 100%, except ethambutol-low level resistance, of which
      the diagnostic sensitivity was 93.4%. After two weeks of incubation in STC
      containing agar proportion methods, one hundred of the 107 strain-drug
      combinations have shown drug resistance, indicating the sensitivity of 93.5%.
      Especially, all 41 isoniazid-resistant strains and 19 of 21 rifampin-resistant
      strains (90.5%) could be detected after two weeks of incubation. A modification
      of the agar proportion method using STC resulted in a reliable and more easily
      interpretable data, and detected most of resistant strains a week earlier than
      conventional method.

PMID- 16563535
TI  - Detection of Fusarium culmorum in wheat by a surface plasmon resonance-based DNA
      sensor.
AB  - A surface plasmon resonance (SPR) sensor based on DNA hybridization has been
      developed for the detection of Fusarium culmorum, a fungal pathogen of cereals. A
      0.57 kbp DNA fragment of F. culmorum was amplified by specific primers and a 25
      mer oligonucleotide probe was selected within the sequence of the PCR amplicon.
      After biotinilation, the probe was immobilized on a streptavidin sensor chip and
      tested for biospecific interaction with PCR products of F. culmorum. The effect
      of denaturating agents (formamide and urea) and ionic strength (NaCl) on
      hybridization efficiency of double-stranded PCR products with the immobilized
      probe and the specificity of the probe were investigated. The SPR biosensor was
      successfully used for the detection of F. culmorum in culture material of
      different strains and in naturally infected wheat samples. Tested on fungal
      cultures, it showed a good selectivity for F. culmorum against other species of
      either Fusarium or other fungal genera. A background signal was observed in wheat
      samples strictly depending on the DNA amount of the testing matrix. Testing 30 ng
      of durum wheat DNA the detection limit was 0.06 pg of F. culmorum DNA. The
      developed PCR-SPR assay allowed to detect F. culmorum with sensitivity and
      specificity higher than gel-electrophoresis analysis.

PMID- 16563536
TI  - Assessment of biases associated with profiling simple, model communities using
      terminal-restriction fragment length polymorphism-based analyses.
AB  - Community profiles based on terminal-restriction fragment length polymorphism (T
      RFLP) analyses of amplified ribosomal RNA genes are used to monitor changes in
      microbial community structure and are sometimes employed for semi-quantitative
      estimates of species richness and abundance in environmental samples. To assess
      the accuracy of T-RFLP community profiles representing the relative abundance of
      bacteria in a sample, five species of ruminal bacteria were used to construct
      simple "communities". Template DNA for PCR amplification was generated either by
      mixing equal quantities of genomic DNA from pure cultures or by mixing equal
      numbers of cells prior to DNA extraction. Pairwise mixtures of Fibrobacter
      succinogenes S85 with Ruminococcus albus 8, Ruminococcus flavefaciens FD-1,
      Butyrivibrio fibrisolvens 49 and Streptococcus bovis JB1 were created and a 5
      member community was constructed. With genomic DNA mixes, relative abundance
      calculations based on T-RFLP patterns did not reflect input ratios. These
      discrepancies could not be accounted for by differences in genome size and rRNA
      operon copy number. In cell mixing experiments, easily lysed cells were
      overrepresented. To determine if a numerical correction factor could be used to
      compensate for observed discrepancies, we attempted to quantify biases attributed
      to DNA extraction and PCR amplification. Biases attributable to these factors led
      to deviations from expected PCR product ratios by 6% to 38%. We found that
      interactions were so complex that a suitable factor could not be derived. The
      unsystematic dependence of T-RFLP peak ratios on variability of DNA extraction
      and PCR amplification prevents accurate quantification of the relative abundance
      of microorganisms designed to represent simplified natural populations.

PMID- 16563537
TI  - The theory of the whole-brain-work.
AB  - The theory of the whole-brain-work basically explains the oscillatory dynamics of
      the human and nonhuman brain during cognitive processing. The theory is based on
      principles according to which brain functions are represented by the oscillatory
      activity. Oscillatory activity in a given frequency band performs multiple
      functions since they vary on a number of response parameters. There is selective
      cooperation in the stimulated brain; this produces super-binding between neural
      populations and super-synergy in the whole brain. The concept of super-synergy
      thus includes super-binding and, additionally, entropy and the role of EEG
      oscillations as control parameters in brain's responsiveness. In super-synergy,
      spatial integration occurs through the selective cooperation of brain structures.
      Temporal integration occurs in line with the principle of superposition of
      oscillations in which the comparative polarity and phase angle are critical for
      forming the function-specific configurations. Extension of the theory of whole
      brain-work to cognitive processing proposes that there is a constant reciprocal
      activation within the subprocesses of attention, perception learning and
      remembering and this leads to an APLR-alliance. In such a context, all brain
      functions are inseparable, for instance, from memory function and, in turn,
      memory states have no exact boundaries along the time space; memory states thus
      evolve in the APLR-alliance. The theory claims that the reentry and the dynamic
      behavior of oscillations during the reciprocal activation in APLR-alliance are
      among the causal factors for brain dynamics and for cognition.

PMID- 16563538
TI  - Rhythmic performance during a whole body movement: dynamic analysis of force-time
      curves.
AB  - The purpose of this study was to investigate rhythmic performance during two
      legged hopping in place. In particular, it was tested whether (a) timing control
      is independent of force control, (b) a dynamic timer model explains rhythmic
      performance, and (c) it is a force related parameter that carries the timing
      information. Eleven participants performed two-legged hopping at their preferred
      hopping frequency (PHF) and at two hopping frequencies set by an external
      rhythmic stimulus as lower (LHF) and higher (HHF) than their PHF, respectively. A
      force plate was used to record the ground reaction force (GRF) time curves during
      two-legged hopping. The primary temporal and force related parameters determined
      from the GRF-time curves were the durations of the cycle of movement (t(cycle)),
      of the contact phase (t(contact)), of the flight phase (t(flight)), the magnitude
      of peak force (Fz(peak)) and the rate of peak force development (RFD). Control of
      t(cycle) was independent of force control as shown by the non-significant
      correlations between t(cycle) and the force parameters of the GRF-time curve. Lag
      1 autocorrelations of t(cycle) were not significant in any of the HF, thereby a
      dynamic timer model is considered to explain the timing of t(cycle) during two
      legged hopping. RFD varied more than any other GRF-time curve parameter,
      exhibited consistent significant strong correlations with the GRF-time curve
      parameters and significant negative lag 1 autocorrelations in PHF, thus, it was
      highlighted as the potent timing control parameter. Finally, we provide a
      practical application for the optimization of rhythmic performance.

PMID- 16563539
TI  - Difference in sensorimotor adaptation to horizontal and vertical mirror
      distortions during ballistic arm movements.
AB  - When learning a novel motor task, the sensorimotor system must develop new
      strategies to efficiently control the limb(s) involved, and this adaptation
      appears to be developed through the construction of a behavioral map known as an
      'internal model'. A common method to uncover the mechanisms of adaptation and
      reorganization processes is to expose the system to new environmental conditions,
      typically by introducing visual or mechanical distortions. The present study
      investigated the adaptation mechanisms of the human sensorimotor system to
      horizontal and vertical mirror distortions (HMD and VMD) during the execution of
      fast goal-directed arm movements. Mirror distortions (MDs) were created by means
      of virtual visual feedback on a computer screen while the movement was executed
      on a graphics tablet. Twenty healthy adult participants were recruited and
      assigned to one of two groups of 10 people each. Tests were divided in two
      subsequent blocks of five trials. The first block consisted of trials with no
      mirror distortion (NMD), while the second block was recorded when exposing one
      group to HMD and the other to VMD. Both MDs resulted in kinematic changes: during
      the tests with the MDs the participants did not reach the performance level found
      at the NMD test. Motor performance during HMD appeared to be globally better than
      during VMD and the adaptation process to VMD appeared to be slower than to HMD,
      but data interpretation was hampered by large within-participant and between
      participant variability. In-depth analyses of the data revealed that most of the
      motor performance information was contained in the direction of movement. The
      data supported the idea that the internal model for HMD was already partially
      built.

PMID- 16563540
TI  - Influence of vision and static stretch of the calf muscles on postural sway
      during quiet standing.
AB  - The purpose of this experimental study was to evaluate the effects of vision and
      stretching of the calf muscles on postural sway during quiet standing. Under pre
      stretch conditions, participants stood on a force plate for 30s and the sway of
      the ground reaction force center of pressure was recorded. The following postural
      sway variables were calculated off-line: sweep speed, sway speed, standard
      deviation, maximal mediolateral range, maximal anteroposterior range, mean
      mediolateral position and mean anteroposterior position. For post-stretch
      conditions, participants stood quietly on a device that was utilized to impose a
      static 3 min ankle joint dorsiflexion stretch. Immediately thereafter,
      participants moved onto the force platform where postural sway parameters were
      again recorded. Randomized eyes-open and eyes-closed conditions were tested in
      both cases. Results showed that postural sway significantly increased due to
      stretch (sweep speed, sway speed, standard deviation, maximal anteroposterior
      range, mean anteroposterior position), as well as eye closure (sweep speed, sway
      speed, standard deviation, maximal mediolateral range, maximal anteroposterior
      range). The interaction between stretch and eye closure was also significant
      (sweep speed, sway speed, standard deviation, maximal mediolateral range),
      suggesting that there were only minor increases in postural sway after stretch
      under the eyes-open condition. It was suggested that stretching of the calf
      muscles has the effect of increasing postural sway, although this effect can be
      greatly compensated for when vision is included.

PMID- 16563541
TI  - Dominance of gait cycle duration in casual walking.
AB  - In gait research, casual walking has been considered to be walking at a casual
      speed. However, it is unclear that walking speed is the most stable factor in
      casual walking compared to other factors such as cycle duration and stride
      length. Although walking speed can be calculated from cycle duration and stride
      length, it is not necessarily the case that these parameters are "stable" in the
      same manner. We therefore conducted an experiment to determine which of these
      three parameters is most stable, regarding walking speed as cycle speed and using
      the coefficient of variation across gait cycles as index of stability. Ten
      participants were invited to walk in their own casual manner, once a week for a
      period of four weeks. Cycle duration was measured by means of a foot switch
      attached to the right heel. To measure the moving distance, participants towed a
      distance meter. Stride length and cycle speed were measured using this device.
      Over the four-week period, cycle duration and stride length were stable, whereas
      cycle speed was the most variable parameter. Furthermore, in the results for each
      single day, the cycle duration was significantly more stable than the other
      parameters. These results suggest that, when we walk casually, cycle duration is
      the dominant factor, rather than stride length or walking speed.

PMID- 16563542
TI  - Prediction of arm trajectory from a small number of neuron activities in the
      primary motor cortex.
AB  - Monkey arm movement was reconstructed from neuron activities recorded in the
      primary motor cortex (Ml). We recorded single neuron activities from a monkey's
      Ml, while the animal performed an arm reaching task. We also recorded
      electromyographic (EMG) activity and movement trajectories during the task.
      First, we reconstructed the EMG signals from the neuron activities. The EMG
      signals were reliably reconstructed with a linear summation of the neuron
      activities. Next, we reconstructed joint angles from the reconstructed EMG
      signals with an artificial neural network model. The reconstructed trajectories
      of the hand position and elbow position showed good correlation with the actual
      arm movement. This model appropriately reflected the anatomical characteristics.

PMID- 16563543
TI  - Retroviral vectors for vaccine development: induction of HIV-1-specific humoral
      and cellular immune responses in rhesus macaques using a novel MLV(HIV-1)
      pseudotype vector.
AB  - Retroviral vectors have yet not been tested for their potential as vaccines
      despite their frequent utilization in gene therapy allowing for highly efficient
      gene transfer into a number of cell types and their suitability for large-scale
      production in biotechnology. To investigate MLV-based vectors suitability for
      inducing immune response against HIV-1-antigens, we generated a MLV(HIV-1)
      pseudotype vector enabling CD4-specific transduction of HIV-1 genes env, vpu, tat
      and rev originating from the pathogenic SHIV-89.6P. Functional expression of the
      lentiviral genes in packaging cells, human and rhesus CD4+ target cells was
      demonstrated by various assays. Following highly efficient ex vivo transduction,
      up to 3.4x10(7) autologous, transfer vector-positive rhesus peripheral blood
      mononuclear cells (rhPBMCs) were re-inoculated into a rhesus macaque. Five weeks
      after the initial inoculation HIV-1 Env-specific antibodies were detected using
      ELISA. ELIspot-assay revealed the induction of a HIV-1 Rev and Env-specific CTL
      response 7.5 weeks after immunization. Thus, these novel MLV(HIV-1) vectors
      facilitate efficient transduction and subsequent expression of HIV-1-genes in CD4
      positive host cells. Induction of both humoral and cellular HIV-1-specific immune
      responses in vivo confirmed their potential as an effective HIV-1 vaccine to be
      further studied in SHIV/rhesus macaque model of lentivirus infection.

PMID- 16563544
TI  - Efficient enantioselective hydrolysis of D,L-phenylglycine methyl ester catalyzed
      by immobilized Candida antarctica lipase B in ionic liquid containing systems.
AB  - Immobilized Candida antarctica lipase B (Novozym 435)-catalyzed enantioselective
      hydrolysis of D,L-phenylglycine methyl ester to enatiopure D-phenylglycine was
      successfully conducted in the systems with ionic liquids (ILs). Novozym 435
      exhibited excellent activity and enantioselectivity in the system containing the
      IL BMIMxBF(4) compared to several typical organic solvents tested. It has been
      found that the cations and, particularly, the anions of ILs have a significant
      effect on the reaction, and the IL BMIMxBF(4), which shows to be the most
      suitable for the reaction, gave the highest initial rate and enantioselectivity
      among various ILs examined. The reaction became much less active and
      enantioselective in the systems with BMIMxHSO(4). Also, it was noticed that the
      enzymatic hydrolysis was strongly dependent on BMIMxBF(4) content in the co
      solvent systems and the favorable content of the IL was 20% (v/v). Of the assayed
      four co-solvents and phosphate buffer, the lowest apparent K(m) and activation
      energy, and the highest V(max) of the reaction were achieved using 20% (v/v)
      BMIMxBF(4) co-solvent with phosphate buffer. Additionally, various influential
      variables were investigated. The optimum pH, substrate concentration, reaction
      temperature and shaking rate were 8.0, 80mM, 25-30 degrees Celsius and 150rpm,
      respectively, under which the initial rate, the residual substrate e.e. and the
      enantioselectivity were 2.46mM/min, 93.8% (at substrate conversion of 53.0%) and
      38, respectively. When the hydrolysis was performed under reduced pressure, the
      initial rate (2.64mM/min) and the enantioselectivity (E=43) were boosted.

PMID- 16563545
TI  - Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced
      enhanced cellular and humoral immune responses in various animal models.
AB  - Microparticles and nanoparticles prepared with poly(D,L-lactide-co-glycolide)
      (PLGA) or poly(D,L-lactide) (PLA) polymers represent a promising method for in
      vivo delivery of encapsulated peptide, protein or DNA antigens. However, one
      major issue that limits the potential of these delivery systems is the
      instability or the degradation of the entrapped antigen. Charged microparticles
      carrying surface adsorbed antigen were developed to resolve this problem and
      appear more suitable for vaccine applications. We describe here new anionic PLA
      nanoparticles obtained by the dialysis method that are absolutely surfactant
      free, which makes them more appropriate for use in humans. The potency of this
      delivery system as a vaccine carrier was tested in various animal models using
      HIV-1 p24 protein. p24-coated PLA nanoparticles (p24/PLA) induced high antibody
      titres (>10(6)) in mice, rabbits and macaques. Moreover, p24/PLA nanoparticles
      elicited strong CTL responses and a Th1-biased cytokine release (IFNgamma, IL-2)
      in mice. p24 protein seemed to generate a more Th1-oriented response when
      administered coated onto the surface of PLA nanoparticles than adjuvanted with
      Freund's adjuvant. Most importantly, the ability of p24/PLA particles to induce
      Th1 responses was also confirmed in the macaque model, since high levels of
      IFNgamma-producing CD4+ T cells and CD8+ T cells could be detected by the ELISPOT
      assay. This protein delivery system confirms the potential of charged
      nanoparticles in the field of vaccine development.

PMID- 16563546
TI  - [Algodystrophy of the lower limbs during pregnancy].
AB  - Algodystrophy (AD) of the lower limbs during pregnancy is rare and probably
      underdiagnosed. The physiopathologic mechanisms remain under discussion and seem
      multiple and complex. This report describes a retrospective survey of 6 patients
      seen between 1993 and 2004 who had algodystrophy of the lower limbs during
      pregnancy. Comparing the clinical, radiological and evolutionary results to the
      literature allows for identifying the main features of AD during pregnancy:
      disease progression during the second or third trimester, preferential
      localization of the left hip associated or not with other lower limb joint
      involvement and decalcification as seen on radiography. Magnetic resonance
      imaging (MRI), which is accurate, specific and non-invasive, is currently the
      exam of choice in early and differential diagnosis. The evolution is favourable
      in a few months, with general recovery without disability.

PMID- 16563547
TI  - [Influence of treatment with botulinum toxine after stroke to control posture].
AB  - OBJECTIVE: To investigate modification of postural control after treatment with
      botulinum toxine in leg muscles of stroke patients. METHODS: We performed a
      retrospective study of stroke patients who benefitted from injection of botulinum
      toxine in leg muscles between June 2003 and October 2004. The assessment before
      and after the injection relied on clinical examination and on posturographic
      recording on 2 force plates with the patient standing, with eyes open performing
      or not a double task consisting of an arithmetic test and with eyes closed. We
      also compared patients to healthy subjects. RESULTS: Eight patients were included
      in the study. Botulinum toxine injection in the leg muscles significantly
      decreased the triceps spasticity, with no change in clinical assessment of
      balance control (Fugl-Meyer scale). The posturographic data show a decrease in
      the area of centre of pressure displacement in the double-task situation after
      the injection. CONCLUSION: Thanks to the posturographic recording in the double
      task situation, we showed a modification of postural control after treatment with
      botulinum toxine in leg muscles of stroke patients.

PMID- 16563548
TI  - Prevalence of type 2 diabetes mellitus of Chinese populations in Mainland China,
      Hong Kong, and Taiwan.
AB  - This article reviews and describes trends and differences in prevalence of type 2
      diabetes mellitus of Chinese populations in Mainland China, Hong Kong and Taiwan
      based on literatures published in the MEDLINE Advanced database (January 1966
      October 2005) in both Chinese and English languages. Chinese populations in Hong
      Kong and Taiwan have significant higher prevalence rates of diabetes than their
      Mainland counterparts, with odds ratios 1.5 (95% confidence intervals: 1.4, 1.7)
      and 2.0 (95% confidence intervals: 1.8, 2.2), respectively in 1995-2003 adjusted
      for age and diagnostic criteria. Using stratified diagnostic criteria; the odds
      ratios in Hong Kong and Taiwan were consistently higher than Mainland China for
      the periods of 1985-1994 and 1995-2003. A large proportion, i.e. 68.6% (95%
      confidence intervals: 67.4%, 69.7%) of diabetic patients remains undiagnosed in
      Mainland China as compared to 52.6% (95% confidence intervals: 49.8%, 55.5%)
      undiagnosed in Hong Kong and Taiwan. The prevalence rates of diabetes and
      impaired glucose tolerance of the Chinese populations rise in older age groups.
      In tandem with economic development and change toward lifestyle that is lack of
      physical activity and rich in high-fat diet, prevalence of diabetes of the
      Chinese populations are on the rise. If the undiagnosed individuals left
      uncontrolled, they are subject to higher risks of developing diabetes and its
      complications. These will increase the burdens of diabetes medically and
      financially.

PMID- 16563549
TI  - The association of total and differential white blood cell count with metabolic
      syndrome in type 2 diabetic patients.
AB  - AIMS: We investigated the relation between total and differential white blood
      cell (WBC) count and metabolic syndrome (MS) in type 2 diabetic patients.
      METHODS: Eight-hundred and twenty-two patients (males 430, females 392, BMI
      25.4+/-3.2 kg/m2, duration of diabetes 5.7+/-6.8 years) were enrolled in this
      study. We measured total WBC count and differential count, anthropometry, blood
      pressure, fasting glucose, insulin and lipid profiles. RESULTS: The number of
      components of MS and prevalence of MS were increased from 1st quartile to 4th
      quartile of WBC count. Total WBC, neutrophil, lymphocyte, monocyte and eosinophil
      counts were increased with the increase of number of components of MS except
      basophil count. Total WBC, neutrophil, lymphocyte, monocyte and eosinophil counts
      were higher in the patients with MS features than those without MS features. WBC
      count was positively correlated with waist circumference (gamma=0.134), systolic
      blood pressure (gamma=0.082), diastolic blood pressure (gamma=0.083),
      triglyceride (gamma=0.241), insulin (gamma=0.222), and HOMA-IR (gamma=0.225), and
      negatively with HDL cholesterol (gamma=-0.146) (p<0.05, respectively).
      CONCLUSIONS: Chronic inflammation, as indicated by a higher WBC count, may be
      related with the increased number of components of MS in type 2 diabetic
      patients.

PMID- 16563550
TI  - Changes in apoptosis and Bcl-2 expression in human hyperglycemic, term placental
      trophoblast.
AB  - Apoptosis and its associated regulatory mechanisms are physiological events
      crucial to the maintenance of placental homeostasis; imbalance of these
      processes, however, such as occurs under various pathological conditions, may
      compromise placenta function and, consequently, pregnancy success. Increased
      apoptosis occurs in the placentas of pregnant women with several developmental
      disabilities, while increased Bcl-2 expression is generally associated with
      pregnancy-associated tumors. Herein, we tested the hypothesis that apoptosis
      associated disturbs might be involved in the placental physiopathology subjected
      to different maternal hyperglycemic conditions. Thus, in the present study we
      investigated and compared the incidence of apoptosis using TUNEL reaction and Bcl
      2 expression, in term-placentas of normoglycemic, diabetic and daily
      hyperglycemic patients. Tissue samples were collected from 37 placentas, being 15
      from healthy mothers with normally delivered healthy babies, and 22 from mothers
      with glucose disturbances. From these latter 22 patients, 10 showed maternal
      daily hyperglycemia and 12 were clinically diabetics. Both Bcl-2 expression and
      apoptotic DNA fragmentation were established and quantified in the trophoblasts
      of healthy mothers. Compared to these reference values, a higher apoptosis index
      and lower Bcl-2 expression were disclosed in the placentas of the diabetic women,
      while in the daily hyperglycemic group, values were intermediate between the
      diabetic and normoglycemic patients. The TUNEL/Bcl-2 index ratio in the placentas
      varied from 0.02 to 0.09 for pregnant normoglycemic and diabetic women,
      respectively, revealing a predominance of apoptosis in the diabetic group. Our
      findings suggest that hyperglycemia may be a key factor evoking apoptosis in the
      placental trophoblast, and therefore, is relevant to diabetic placenta function.

PMID- 16563551
TI  - Implementation of neuroreflexotherapy for subacute and chronic neck and back pain
      within the Spanish public health system: audit results after one year.
AB  - Controlled randomized trials have demonstrated the efficacy, safety,
      effectiveness, and cost-effectiveness of neuroreflexotherapy (NRT) for the
      management of non-specific back pain. In this audit study, we describe the
      implementation of NRT into the routine practice of primary care within the
      Spanish public health service of the Balearic Islands and the results obtained
      after one year (2004). A referral protocol was made available to all general
      practitioners (GPs) who could refer eligible patients to specialized units in
      performing NRT interventions. A total of 1209 patients (median age 52 years, 68%
      women) were referred to NRT by 412 GPs (80% of all GPs), with a mean (standard
      deviation (S.D.)) referral rate of 1.57 (0.84) patients per month/10,000 persons
      affiliated to each practice, and an appropriate referral rate of 95.5%. Pain
      decreased from a median score (visual analog scale) of 8 at baseline to 1 at
      discharge, referred pain from 7 to 1, and disability (Roland-Morris
      Questionnaire) from 12 to 1. NRT was refused by 2.7% of patients. Adverse effects
      related to the procedure were only a skin reaction in 3.3% of patients. We
      conclude that it is feasible to implement NRT in the public health service
      complying with methods and application conditions used in previous randomized
      controlled trials (RCTs). In such conditions, implementation of this technology
      obtained positive audit results at one year.

PMID- 16563552
TI  - Deblurring visual evoked potentials using commercially available software.
AB  - Visual evoked potentials are useful clinical tools to study visual pathways of
      the brain. Although the temporal resolution is unsurpassed by other brain imaging
      technologies, the spatial resolution is diminished or blurred by the low
      conductance of the electrical signals through the skull. Methods have been
      proposed to improve the spatial resolution by downwardly projecting the
      electrical signals measured on the scalp to the surface of the cerebral cortex
      through the inverse solution of the equations governing static current flow. We
      describe the adaptation and combination of commercially available engineering
      software programs to solve this inverse problem and report the results of a
      sample run of the system. Before deblurring, the visual evoked potentials
      appeared to be diffusely localized over the posterior scalp. After deblurring,
      the visual evoked potentials were only found at the electrodes closest to the
      visual cortex, as would be predicted by our current knowledge of neuroanatomy.

PMID- 16563553
TI  - A neural approach to extract foreground from human movement images.
AB  - In recent years many approaches to foreground extraction from images related to
      human movement have been presented. The foreground extraction represents a pre
      processing procedure to be implemented in a system for capturing human movement
      in order to facilitate the tracking of anatomical landmarks on human bodies. In
      this work, an approach based on an unsupervised neural network has been studied:
      a Kohonen map has been designed to recognize and separate structures
      characterizing foreground and background. The proposed technique is fully
      automatic and its performance has been compared with those of two further
      approaches based on differences between foreground and background images. In
      order to quantify the segmentation quality, an already validated, objective, and
      automatic criterion has been used. The obtained results are adequate with the
      final aim of the application and show the feasibility of the proposed approach.

PMID- 16563554
TI  - Real-time calculation and visualization of spectra in field-cycled dynamic
      nuclear polarization spectroscopy.
AB  - Field-cycled dynamic nuclear polarization (FC-DNP), which is based on the
      Overhauser effect, provides a new way to perform in vivo measurements of free
      radicals in biological systems. Since it measures the alterations of the nuclear
      magnetic resonance (NMR) signal in the presence of paramagnetic molecules, a
      customized program is usually needed in FC-DNP experiments to extract spectral
      information from the acquired NMR signals. While this program can be designed to
      calculate the spectrum after all the NMR signals are collected, the batch
      processing mode inevitably causes delay and is not convenient for in vivo
      applications. In this paper, we report the development of a real-time DNP
      spectrum calculation and visualization program, called RT_DNP, for FC-DNP
      experiments. A dynamic data exchange (DDE) client was implemented to enable real
      time receipt of the system information and the NMR signals from a commercial NMR
      console. The received NMR signals and experimental parameters were then used to
      calculate the DNP spectrum during the data acquisition. The real-time DNP
      spectrum calculation and visualization program was tested in experiments. A
      seamless integration of the program into a commercial NMR console has been
      achieved.

PMID- 16563555
TI  - Drug-eluting stents: an innovative multidisciplinary drug delivery platform.

PMID- 16563556
TI  - Drug delivery in degenerative joint disease.

PMID- 16563557
TI  - Gene therapeutic approaches-transfer in vivo.
AB  - Osteoarthritis (OA) is common, debilitating, expensive, incurable and very
      difficult to treat. Gene transfer to the synovial linings of affected joints is a
      promising strategy for achieving sustained, therapeutic, intraarticular
      concentrations of anti-arthritic gene products. This is not reasonably possible
      with existing, alternative technologies. The present review summarizes progress
      in achieving direct, in vivo intraarticular gene delivery and expression.
      Numerous non-viral vectors have been evaluated for their ability to transfect the
      synovia of experimental animals following intraarticular injection. None have
      given more than low levels of temporary transgene expression and many are
      inflammatory. Several viral vectors, however, are very effective in this regard
      and successfully treat experimental models of OA. Adeno-associated virus has been
      used in a phase I study for the gene therapy of rheumatoid arthritis. Its use in
      a clinical trial for treating OA is pending.

PMID- 16563558
TI  - Phase II study of the combination of gemcitabine and nedaplatin for advanced non
      small-cell lung cancer.
AB  - We examined the efficacy and safety of the combination of gemcitabine and
      nedaplatin in patients with untreated advanced non-small-cell lung cancer. Thirty
      four patients (24 men and 10 women) with a mean age of 69 years (range, 39-75
      years) were treated every 3 weeks with gemcitabine (1,000 mg/m(2) on days 1 and
      8) and nedaplatin (100 mg/m(2) on day 1). Four patients had stage IIIB disease
      and 30 patients had stage IV disease. None of the 33 patients achieved a complete
      response, but 10 achieved a partial response, for a response rate of 30.3% (95%
      confidence interval, 15.6-48.7%). One patient could not be evaluated for response
      because only one course of chemotherapy had been administered due to grade 3
      eruption. The median survival time was 9.0 months (range, 1-17 months). Grades 3
      4 hematological toxicities included leukopenia in 47% of patients, neutropenia in
      62%, thrombocytopenia in 56%, and anemia in 44%. Grades 3-4 nonhematological
      toxicities included nausea and vomiting in 6% of patients, diarrhea in 3%, and
      hepatic dysfunction in 9%. There were no treatment-related deaths. The dose
      intensities were 89.6% and 86.7%, respectively, of the planned doses of
      gemcitabine and nedaplatin. Our results suggest that the combination of
      gemcitabine and nedaplatin is an acceptable treatment for patients with
      previously untreated advanced non-small-cell lung cancer.

PMID- 16563559
TI  - A multicenter phase II study of sequential vinorelbine and cisplatin followed by
      docetaxel and gemcitabine in patients with advanced non-small cell lung cancer.
AB  - PURPOSE: To evaluate the activity and toxicity of the sequential administration
      of vinorelbine/cisplatin (VC regimen) followed by the docetaxel/gemcitabine (DG
      regimen) combination in patients with advanced non-small cell lung cancer
      (NSCLC). PATIENTS AND TREATMENT: Fifty-nine previously untreated patients with
      advanced/metastatic NSCLC received three cycles of cisplatin 80 mg/m(2) (day 1),
      and vinorelbine 30 mg/m(2) (days 1 and 8 every 3 weeks; VC regimen), followed by
      six cycles of docetaxel (65 mg/m(2), day 1) and gemcitabine (1,500 mg/m(2), day
      1), (DG regimen) every 2 weeks. RESULTS: One (1.7%) complete and 26 (44.1%)
      partial responses were achieved for an overall response rate of 45.8% (95% CI
      33.05-58.48%); 12 (20.3%) patients had stable disease and 20 (33.9%) progressive
      disease. The median time to progression was 5.3 months, the median survival time
      12.5 months and the 1-year survival rate 51%. The main toxicity was grade III/IV
      neutropenia occurring in 25.5% of patients; all other hematologic and non
      hematologic toxicities were relatively infrequent. CONCLUSIONS: The sequential
      administration of VC and DG regimens was well tolerated and active against
      advanced NSCLC and merits to be further evaluated against a single doublet.

PMID- 16563560
TI  - Recombinant GM-CSF plus autologous tumor cells as a vaccine for patients with
      mesothelioma.
AB  - Treatments evaluated for malignant mesothelioma (MM), including chemotherapy,
      radiotherapy and surgery are of limited efficacy. Immunotherapy has shown some
      promise in MM but optimal vaccination conditions are yet to be defined.
      Autologous tumour vaccines have the advantage of containing both 'self'- and
      'neo'-tumor antigens but they are not commonly used in any cancer, and never in
      MM. We therefore evaluated the effect of an autologous MM tumor cell lysate,
      given s.c. with recombinant granulocyte-macrophage colony stimulating factor (GM
      CSF), on anti-tumor immunity in patients with MM. PATIENTS AND METHODS: An
      autologous tumor lysate vaccine was manufactured from surgically resected tumor
      and administered subcutaneously together with GM-CSF. Induction of tumor specific
      cellular immunity was assessed by delayed type hypersensitivy (DTH) skin testing
      using autologous tumor tissue and of humoral immune responses to shared MM
      antigens by western blotting of patients' sera against a panel of allogeneic
      human MM cell lines. CT scanning was used to evaluate tumor progression. RESULTS:
      Twenty-two patients were enrolled onto the trial. Of these five developed
      positive delayed type hypersensitivity skin tests and five showed evidence of
      altered antibody specificities by western blotting. A total of seven patients
      developed at least one type of anti-MM immune response. On an intention-to-treat
      basis the median survival of all patients was 11.5 months, and the 1- and 2-year
      survival rates were 50% and 27%, respectively. Complete or partial CT responses
      were not seen, however seven patients had stable disease for the duration of the
      trial. Vaccination was safe with no severe adverse reactions. CONCLUSION:
      Vaccination with autologous MM tumor cell lysate with GM-CSF induced tumor
      specific immunity in 32% of patients, was safe and was associated with stable
      disease but no major tumour regressions.

PMID- 16563561
TI  - Transport and anaerobic biodegradation of propylene glycol in gravel-rich soil
      materials.
AB  - Continued input of airplane de-icing/anti-icing fluids (ADAF) to runway adjacent
      soils may result in the depletion of soil-borne terminal electron acceptors. We
      studied the transport and transformation of propylene glycol (PG), the major
      constituent of many ADAF, in topsoil and subsoil samples using saturated column
      experiments at 4 degrees C and 20 degrees C. The export of soil-borne DOC was
      generally high, non-exhaustive and rate limited. Retardation of added PG was
      negligible. Rapid PG degradation was observed only in topsoil materials high in
      organic matter at 20 degrees C. At 4 degrees C, no significant degradation was
      observed. Thus, under unfavorable, i.e., wet and cold conditions typical for
      winter de-icing operations, PG and its metabolites will be relocated to deeper
      soil horizons or even to the groundwater. In subsoil materials, PG degradation
      was very slow and incomplete. We found that subsoil degradation depended on the
      import of active microorganisms originating from the organic-rich topsoil
      material. The degradation efficiency is strongly influenced by the flow velocity,
      i.e., the residence time of PG in the soil column. Poorly crystalline iron(III)
      and manganese(IV) (hydr)oxides are used during microbial respiration acting as
      terminal electron acceptors. This results in the formation and effective
      relocation of reduced and mobile Fe and Mn species. Long-term application of ADAF
      to runway adjacent soil as well as the lasting consumption of Fe and Mn will tend
      to decrease the soil redox potential. Without proper counteractive measures, this
      will eventually favor the development of methanogenic conditions.

PMID- 16563562
TI  - 2004 Lowbury Lecture: the Western Australian experience with vancomycin-resistant
      enterococci - from disaster to ongoing control.
AB  - The first hospital outbreak of a vancomycin-resistant enterococcus (VRE) in
      Western Australia (WA) started in the Royal Perth Hospital in July 2001 and
      initially involved the Intensive Care Unit (ICU) and the Nephrology and Dialysis
      Units. The outbreak was caused by vancomycin-resistant Enterococcus faecium
      (VREF) of the vanB genotype. Pulsed-field gel electrophoresis and plasmid
      analysis of the isolates demonstrated a single-strain outbreak. Despite the
      isolation of carriers and implementation of all the additional precautions
      recommended to control VRE, VREF spread rapidly. Two months after the index
      patient was detected, the epidemic strain had spread to 22 wards and units and
      one outpatient unit (Satellite Dialysis). Four patients were infected and 64 were
      colonized. A Hospital VRE Executive Group, which included the Chief Executive and
      Directors of Clinical Services and Nursing, was formed to eradicate the outbreak
      and to prevent the epidemic strain from becoming endemic in the hospital. The WA
      Department of Health agreed to provide substantial extra funding to enable the
      hospital to use expensive enhanced infection control practices, as follows.
      Control was handicapped by the slowness of conventional laboratory methods, which
      took four to five days to identify VRE and allowed environmental contamination
      and nosocomial transmission to occur before carriers were detected and isolated.
      A laboratory procedure to make rapid provisional identification of VRE within 30
      48h was developed by performing multiplex polymerase chain reaction (PCR) for
      vanA and vanB genes directly on 24-h selective enrichment broth cultures. On
      average, four rectal swabs, each collected on separate days, were needed to
      detect >90% of carriers. In total, 1977 ward contacts were screened after
      discharge from hospital and 54 (2.73%) were found to be carrying VREF. The
      electronic labelling and active follow-up of ward contacts resulted in a
      significant number of carriers being detected who otherwise posed a risk of
      initiating further outbreaks in hospital if they were re-admitted. The outbreak
      was terminated after five months and the cost of the enhanced infection control
      practices was 2,700 000 Australian dollars (1,000,000 pounds sterlings). Ongoing
      control has been facilitated by targeted active surveillance cultures: on
      admission to high-risk units (ICU, Burns, Nephrology, Haematology, Bone Marrow
      Transplant Unit), on transfer out of the ICU to other hospital units, by monthly
      screening of patients regularly attending Dialysis Units, and by opportunistic
      laboratory screening of inpatient faecal specimens submitted for Clostridium
      difficile culture and toxin. Vigilance needs to be maintained as the epidemic
      strain of VREF remains in the Perth community. Ward contacts of the first
      outbreak have caused small outbreaks in two hospitals, and seven to 19 sporadic
      new carriers have been detected annually since the first outbreak. The key
      elements of the VRE control programme are as follows: To date, this programme has
      prevented VRE from becoming established in any WA hospital.

PMID- 16563563
TI  - Effect of fatty acid chain length on suppression of ghrelin and stimulation of
      PYY, GLP-2 and PP secretion in healthy men.
AB  - We have evaluated the effects of fatty acid chain length on ghrelin, peptide YY
      (PYY), glucagon-like peptide-2 (GLP-2) and pancreatic polypeptide (PP) secretion
      and hypothesized that intraduodenal administration of dodecanoic ("C12"), but not
      decanoic ("C10"), acid would decrease plasma ghrelin and increase PYY, GLP-2 and
      PP concentrations. Plasma hormone concentrations were measured in seven healthy
      men during 90-min intraduodenal infusions of: (i) C12, (ii) C10 or (iii) control
      (rate: 2 ml/min, 0.375 kcal/min for C12/C10) and after a buffet-meal consumed
      following the infusion. C12 markedly suppressed plasma ghrelin and increased both
      PYY and GLP-2 (all P < 0.05) compared with control and C10, while C10 had no
      effect. Both C10 and C12 increased PP concentrations slightly (P < 0.05). We
      conclude that the effects of intraduodenal fatty acids on ghrelin, PYY and GLP-2
      secretion are dependent on their chain length.

PMID- 16563564
TI  - Increased levels of pregnenolone and its neuroactive metabolite allopregnanolone
      in autopsied brain tissue from cirrhotic patients who died in hepatic coma.
AB  - It has been suggested that neurosteroids with agonist properties at the central
      GABA-A receptor are implicated in the pathogenesis of hepatic encephalopathy (HE)
      in chronic liver disease. In order to address this issue, gas chromatography/mass
      spectrometry was used to measure the neurosteroids pregnenolone,
      allopregnanolone, and tetrahydrodeoxycorticosterone (THDOC) in postmortem brain
      tissue from controls, cirrhotic patients who died without HE, a patient who died
      in uremic coma, and cirrhotic patients who died in hepatic coma. Exposure of rat
      cerebral cortical membranes to brain extracts from hepatic coma patients resulted
      in a 53% (p < 0.001) increase in binding of [3H]muscimol, a GABA-A receptor
      ligand. Subsequent GC/MS analysis showed that concentrations of the GABA-A
      receptor agonist neurosteroid allopregnanolone were significantly increased in
      brain tissue from hepatic coma patients compared to patients without HE or
      controls (p < 0.001). Brain allopregnanolone concentrations were significantly
      correlated with the magnitude of induction of [3H]muscimol binding (r2 = 0.82, p
      < 0.0001). Concentrations of allopregnanolone comparable to those observed in
      hepatic coma brains are pathophysiologically relevant. Concentrations of the
      neurosteroid precursor pregnenolone were also increased in brain tissue from
      hepatic coma patients, while those of a second neurosteroid THDOC were below the
      levels of detection in all groups. Brain concentrations of benzodiazepine
      receptor ligands estimated by radioreceptor assay were not significantly
      increased in cirrhotic patients with or without hepatic coma. These findings
      suggest that increased levels of allopregnanolone rather than "endogenous
      benzodiazepines" offer a cogent explanation for the phenomenon of "increased
      GABAergic tone" previously proposed in HE.

PMID- 16563565
TI  - Neurobiological characterization of an azoxymethane mouse model of acute liver
      failure.
AB  - Molecular biological approaches continue to lead to the identification of
      alterations in expression of genes coding for key central nervous system proteins
      involved in water homeostasis, energy metabolism and neurotransmitter regulation
      in acute liver failure (ALF). However, studies aimed at elucidating the
      pathophysiological consequences of these changes in gene expression are impeded
      by the lack of a suitable mouse model of ALF. A previous report described hepatic
      pathology characteristic of ALF resulting from the administration of azoxymethane
      (AOM) in mice [Matkowskyj, K.A., Marrero, J.A., Carroll, R.E., Danilkovich, A.V.,
      Green, R.M., Benya, R.V., 1999. Azoxymethane-induced fulminant hepatic failure in
      C57BL/6J mice: characterization of a new animal model. Am. J. Physiol. 277, G455
      G462]. In a series of experiments to further assess this treatment as an
      effective model of ALF, the effects of administration of AOM to male C57BL mice
      on hepatic and cerebral function were studied. With maintenance of body
      temperature at 37 degrees C and control of hypoglycemia, mice developed signs of
      encephalopathy (decreased locomotor activity followed by loss of righting and
      corneal reflexes) within 16 h of AOM treatment. AOM-treated mice were
      hyperammonemic, developed spontaneous hypothermia and brain edema. Brain ammonia
      concentrations were increased to 0.98+/-0.12 mM at coma stages of encephalopathy.
      Brain amino acid profiles determined by HPLC were typical of ALF in other species
      including humans. Mild hypothermia (35 degrees C) led to significant attenuation
      of brain edema, ammonia, and amino acid changes. These findings demonstrate that
      AOM treatment affords a simple, reproducible mouse model of ALF which may be
      suitable for the study of the effects of gene manipulation on the cerebral
      complications of ALF.

PMID- 16563566
TI  - Brain ferritin iron may influence age- and gender-related risks of
      neurodegeneration.
AB  - BACKGROUND: Brain iron promotes oxidative damage and protein oligomerization that
      result in highly prevalent age-related proteinopathies such as Alzheimer's
      disease (AD), Parkinson's disease (PD), and Dementia with Lewy Bodies (DLB). Men
      are more likely to develop such diseases at earlier ages than women but brain
      iron levels increase with age in both genders. We hypothesized that brain iron
      may influence both the age- and gender-related risks of developing these
      diseases. METHODS: The amount of iron in ferritin molecules (ferritin iron) was
      measured in vivo with MRI by utilizing the field dependent relaxation rate
      increase (FDRI) method. Ferritin iron was measured in four subcortical nuclei
      [caudate (C), putamen (P), globus pallidus (G), thalamus (T)], three white matter
      regions [frontal lobe (Fwm), genu and splenium of the corpus callosum (Gwm, Swm)]
      and hippocampus (Hipp) in 165 healthy adults aged 19-82. RESULTS: There was a
      high correlation (r>0.99) between published post-mortem brain iron levels and
      FDRI. There were significant age-related changes in ferritin iron (increases in
      Hipp, C, P, G, and decreases in Fwm). Women had significantly lower ferritin iron
      than men in five regions (C, T, Fwm, Gwm, Swm). CONCLUSIONS: This is the first
      demonstration of gender differences in brain ferritin iron levels. It is possible
      that brain iron accumulation is a risk factor that can be modified. MRI provides
      the opportunity to assess brain iron levels in vivo and may be useful in
      targeting individuals or groups for preventive therapeutic interventions.

PMID- 16563568
TI  - The leukocyte expression of CD36 is low in patients with Alzheimer's disease and
      mild cognitive impairment.
AB  - CD36, a scavenger receptor of class B (SR-B), helps mediate microglial and
      macrophage response to beta-amyloid fibrils (betaA), and seems to play a key role
      in the proinflammatory events associated with Alzheimer disease (AD) in many
      tissues. Peripheral leukocytes express many molecules and multiple receptors
      which undergo the same regulatory mechanisms as those operative in the brain.
      Thus, these cells, easily obtainable through peripheral blood sampling, may be
      used as a tool to investigate changes occurring in inaccessible brain areas.
      Based on these premises, we investigated the leukocyte expression of CD36 in 70
      AD patients and in 30 subjects with mild cognitive impairment (MCI). Results were
      compared to those of 20 young and 40 age-matched control subjects. Leukocyte
      expression of CD36 was significantly reduced versus controls in both AD and MCI
      patients, while in young and old controls there were no age-related changes.
      Although preliminary, these data indicate that the reduction of CD36 expression
      in leukocytes is a disease-related phenomenon, occurring since the early stages
      of AD (MCI). Irrespective of the mechanism(s) underlying such changes, assessment
      of leukocyte CD36 expression might represent an useful tool to support the
      diagnosis of AD and to screen MCI patients candidates to develop the disease.

PMID- 16563567
TI  - Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in
      Parkinson disease.
AB  - Glutamatergic pathways play a key role in the functional organization of neuronal
      circuits involved in Parkinson disease (PD). Recently, three vesicular glutamate
      transporters (VGLUT1-3) were identified. VGLUT1 and VGLUT2 are responsible for
      the uploading of glutamate into synaptic vesicles and are the first specific
      markers of glutamatergic neurons available. Here, we analyzed the expression of
      VGLUT1 and VGLUT2 in autopsy tissues of PD patients and matched controls using
      Western blot and immunoautoradiography. VGLUT1 and VGLUT2 expression was
      increased in the Parkinsonian putamen by 24% and 29%, respectively (p<0.01). In
      contrast, only VGLUT1 was dramatically decreased in the prefrontal and temporal
      cortex of PD patients (approximately 50%, p<0.01 and p<0.001, respectively).
      These findings demonstrate the existence of profound alterations of glutamatergic
      transmission in PD, which are likely to contribute to the motor and cognitive
      impairments associated with the disease, and should thus be taken into account in
      the treatment of PD.

PMID- 16563569
TI  - Synthesis and evaluation of antifungal activity of naphthoquinone derivatives.
AB  - 3-Arylamino-2-phenylsulfinylnaphthoquinones, 2,3-diarylthio-naphthoquinones and 2
      phenylsulfinyl-3-arylthio-1,4-dihydronaphtalenes are synthesized and tested
      against five fungi. The activities of these products were better than
      amphotericine B against all the strains except for Candida albicans.

PMID- 16563570
TI  - Microwave assisted synthesis of fragrant jasmone heterocyclic analogues.
AB  - cis-Jasmone, from jasmonoid group, is an important jasmine odor fragrance
      compound. The syntheses of new heterocyclic analogues of jasmone were described.
      Five analogues of this compound were prepared under microwave irradiation and the
      results of the microwave assisted syntheses were compared with classical,
      thermally initiated reactions in solvent. Microwave reactions were carried out
      successfully, and reaction times were significantly reduced to a few minutes.
      Three of five obtained analogues, pyrrolidinone, oxazolidinone and thiazolidinone
      demonstrated an interesting, specific odor which was compared with floral,
      typical jasmine odor of jasmone.

PMID- 16563571
TI  - [Human herpesvirus 6 encephalitis in trimethoprim-sulfamethoxazole-induced
      hypersensitivity syndrome].
AB  - INTRODUCTION: Human herpesvirus 6 (HHV-6), the causative agent of the common
      exanthem subitum, is a known cause of central nervous system infection in
      immunocompromised patients. It has been suggested that HHV-6 participate in the
      development of drug-induced hypersensitivity syndrome. CASE REPORT: We reported a
      case of HHV-6 encephalitis associated with hypersensitivity syndrome induced by
      trimethoprim-sulfamethoxazole in a 72-year-old HIV-negative woman. DISCUSSION:
      Our case confirmed that reactivation of HHV-6 infection may contribute to the
      development of the hypersensitivity syndrome.

PMID- 16563573
TI  - [Phototype, vitamin D status and bone mineral density among women at risk of
      osteoporosis].
AB  - PURPOSE: The aim of this study was to test the influence of phototype and vitamin
      D status feature on the bone mineral density (BMD) of the femoral neck in a group
      of middle-aged women considered at risk of osteoporosis (low levels of vitamin D
      [25(OH)D3<78 nmol/L] and hyperparathyroidism [parathormone level>36 pg/mL]).
      METHODS: This two-step study was conducted on 122 French women enrolled in the
      SUVIMAX (supplementation en vitamines et mineraux antioxydants: antioxidant
      vitamin and mineral supplementation) cohort. The impact of various variables on
      BMD, including age, body mass index (BMI), vitamin D status, alcohol intake, sun
      exposure intensity and phototype was investigated using regression models.
      RESULTS: No statistical link was found between BMD and the variables documenting
      vitamin D status and parathormone levels, nor phototype. Nevertheless, fair
      phototypes tended to be associated with lower BMD values. However, BMD decreased
      with age and increased with BMI and physical activity level. CONCLUSIONS:
      Whatever their phototype, adult women concerned about precarious vitamin D status
      should undergo a vitamin D supplementation in combination with an adequate
      calcium intake all year long and a proper sun protection. Moreover, a physical
      activity maintenance should provide an additional benefit for prevention of
      osteoporosis.

PMID- 16563572
TI  - [Pseudo-autoinflammatory attacks of temporal arteritis].
AB  - INTRODUCTION: Usually, temporal arteritis progresses as a chronic disease. CASE
      REPORT: The authors report the observation of a 74-year-old woman who presented
      with two acute flares of temporal arteritis with headache, fever and inflammatory
      syndrome, which have spontaneously resolved. DISCUSSION: The observations of auto
      inflammatory attacks of arteritis disease are rare, but maybe underestimated. The
      pathophysiology remains unclear.

PMID- 16563574
TI  - [18FDG PET: a new criterion for disease activity in Takayasu arteritis].
AB  - INTRODUCTION: Takayasu arteritis (TA) is an inflammatory arteritis affecting
      large vessels, predominantly the aorta, its main branches, and the pulmonary
      arteries. Up to now, arteriography was considered as the "gold standard". But
      others exams are emerging in the management of TA: vascular ultrasound, angio
      scanner, magnetic resonance imaging and 18FDG positron emission tomography (18FDG
      PET). Such investigations allow a study of the lumen but also of the arterial
      walls. However, at the time, no biological or radiological test is able to
      determine the activity of TA. 18FDG PET could be effective to estimate the
      disease activity. EXEGESIS: We report the case of a young woman for who 18FDG PET
      permit to assert a relapse of TA. CONCLUSION: 18FDG PET could be effective to
      estimate the disease activity.

PMID- 16563575
TI  - DNA vaccines expressing B and T cell epitopes can protect mice from FMDV
      infection in the absence of specific humoral responses.
AB  - Despite foot-and-mouth disease virus (FMDV) being responsible for one of the most
      devastating animal diseases, little is known about the cellular immune mechanisms
      involved in protection against this virus. In this work we have studied the
      potential of DNA vaccines based on viral minigenes corresponding to three major B
      and T-cell FMDV epitopes (isolate C-S8c1) originally identified in natural hosts.
      The BTT epitopes [VP1 (133-156)-3A (11-40)-VP4 (20-34)] were cloned into the
      plasmid pCMV, either alone or fused to ubiquitin, the lysosomal targeting signal
      from LIMPII, a soluble version of CTLA4 or a signal peptide from the human prion
      protein, to analyze the effect of processing through different antigenic
      presentation pathways on the immunogenicity of the FMDV epitopes. As a first step
      in the analysis of modulation exerted by these target signals, a FMDV infection
      inhibition assay in Swiss outbred mice was developed and used to analyze the
      protection conferred by the different BTT-expressing plasmids. Only one of the 37
      mice immunized with minigene-bearing plasmids developed specific neutralizing
      antibodies prior to FMDV challenge. As expected, this single mouse that had been
      immunized with the BTT tandem epitopes fused to a signal peptide (pCMV-spBTT) was
      protected against FMDV infection. Interestingly, nine more of the animals
      immunized with BTT-expressing plasmids did not show viremia at 48 h post
      infection (pi), even in the absence of anti-FMDV antibodies prior to challenge.
      The highest protection (50%, six out of 12 mice) was observed with the plasmid
      expressing BTT alone, indicating that the targeting strategies used did not
      result in an improvement of the protection conferred by BTT epitopes.
      Interestingly, peptide specific CD4+ T-cells were detected for some of the BTT
      protected mice. Thus, a DNA vaccine based on single FMDV B and T cell epitopes
      can protect mice, in the absence of specific antibodies at the time of challenge.
      Further work must be done to elucidate the mechanisms involved in protection and
      to determine the protective potential of these vaccines in natural FMDV hosts.

PMID- 16563576
TI  - Periosteal distraction osteogenesis: preliminary experimental evaluation in
      rabbits and dogs.
AB  - The aim of this project was to evaluate the potential of bone formation by the
      distraction of periosteum. Distraction of calvarial bone in 12 rabbits at 0.25 mm
      a day caused formation of bone in 3 animals, and distraction at 0.5mm a day
      caused formation of bone in 2. A second trial of alveolar distraction in four
      dogs using a specifically-designed distraction device showed lack of stability of
      the device.

PMID- 16563577
TI  - Arteriovenous vascular malformations confined to the hand: an algorithm of
      management based on a new classification.
AB  - Management of arteriovenous malformations confined to the hand is diverse and
      ranges from conservative measures to amputation. This paper is a retrospective
      review of 13 patients with arteriovenous malformations of the hand who were
      managed using an algorithm of treatment which considered the clinical
      presentation and the anatomical structure of the lesion.

PMID- 16563578
TI  - Maternal transfer of organohalogen contaminants and metabolites to eggs of Arctic
      breeding glaucous gulls.
AB  - Eggs of seabirds have routinely been used as indicators of environmental
      pollution in the Arctic. However, the variability in organohalogen concentration
      and composition associated with the laying sequence, have not been defined. We
      examined a suite of PCBs, organochlorine (OC) pesticides and by-products,
      polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs) and
      methylsulfonyl- (MeSO2) PCBs in complete 3-egg clutches of glaucous gulls (Larus
      hyperboreus), and plasma samples of the laying females collected from the
      Norwegian Arctic. SigmaPCB, SigmaOC and SigmaPBDE, but not SigmaMeSO2-PCB,
      concentrations in eggs were positively associated, with increasing magnitude and
      significance from the first through the last-laid egg, with concentrations in
      female plasma. However, the concentrations of these organohalogen classes
      fluctuated irrespective of the laying order in the clutch. In general, maternal
      transfer favored low K(ow) and/or less persistent compounds, whereas the
      recalcitrant and/or higher-halogenated compounds were less readily transferred,
      and consequently more selectively retained in the mother.

PMID- 16563579
TI  - Spatial distribution and vertical variation of arsenic in Guangdong soil
      profiles, China.
AB  - Total of 260 soil profiles were reported to investigate the arsenic spatial
      distribution and vertical variation in Guangdong province. The arsenic
      concentration followed an approximately lognormal distribution. The arsenic
      geometric mean concentration of 10.4 mg/kg is higher than that of China. An upper
      baseline concentration of 23.4 mg/kg was estimated for surface soils. The
      influence of soil properties on arsenic concentration was not important. Arsenic
      spatial distributions presented similar patterns that high arsenic concentration
      mainly located in limestone, and sandshale areas, indicating that soil arsenic
      distribution was dependent on bedrock properties than anthropogenic inputs.
      Moreover, from A- to C-horizon arsenic geometric mean concentrations had an
      increasing tendency of 10.4, 10.7 to 11.3 mg/kg. This vertical variation may be
      related to the lower soil organic matter and soil degradation and erosion.
      Consequently, the soil arsenic export into surface and groundwaters would reach
      1040 t year-1 in the study area.

PMID- 16563580
TI  - Polyurethane foam (PUF) disks passive air samplers: wind effect on sampling
      rates.
AB  - Different passive sampler housings were evaluated for their wind dampening
      ability and how this might translate to variability in sampler uptake rates.
      Polyurethane foam (PUF) disk samplers were used as the sampling medium and were
      exposed to a PCB-contaminated atmosphere in a wind tunnel. The effect of outside
      wind speed on PUF disk sampling rates was evaluated by exposing polyurethane foam
      (PUF) disks to a PCB-contaminated air stream in a wind tunnel over air velocities
      in the range 0 to 1.75 m s-1. PUF disk sampling rates increased gradually over
      the range 0-0.9 m s-1 at approximately 4.5-14.6 m3 d-1 and then increased sharply
      to approximately 42 m3 d-1 at approximately 1.75 m s-1 (sum of PCBs). The results
      indicate that for most field deployments the conventional 'flying saucer' housing
      adequately dampens the wind effect and will yield approximately time-weighted air
      concentrations.

PMID- 16563581
TI  - Characterization of polychlorinated dibenzo-p-dioxins and dibenzofurans in
      different particle size fractions of marine sediments.
AB  - The distribution of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs)
      was examined according to particle size in marine sediments, with a particular
      focus on fine particulates. Samples from different coastal sites were
      fractionated into five size groups (<2, 2-5, 5-10, 10-20, and 20-63 microm
      diameter) by gravitational split-flow thin fractionation. Despite the different
      size profiles and PCDD/F contents of the sediments at each site, PCDD/F levels in
      fractionations tended to increase as the particle size decreased; the PCDD/F
      levels in the finest particles were up to 16 times higher than in the coarsest
      particles, which was associated with their organic carbon contents. Log
      normalization showed high levels of PCDD/Fs in the fine silt particles (2-10
      microm), which are consumable by aquatic biota. Because of the different toxicity
      and bioavailability of PCDD/Fs in different sediment particle sizes, it is
      important to study particle actions to understand their effects on the aquatic
      ecosystem.

PMID- 16563582
TI  - Computational fluid dynamic modeling of two passive samplers.
AB  - To effectively use a passive sampler for monitoring trace contaminants in the gas
      phase, its sampling characteristics as a function of ambient wind conditions must
      be known. In this study two commonly used passive samplers were evaluated using
      computational fluid dynamics. Contaminant uptake by the polyurethane foam (PUF)
      was modeled using a species transport model. The external-internal flow
      interactions in the sampler were characterized, and the uptake rates of
      contaminant species were quantified. The simulations show that flow fields in the
      samplers have strong velocity gradients, and single-point velocity measurements
      do not capture flow interactions accurately. Sampling rates calculated for a PUF
      in freestream are in good agreement with sampling rates for PUFs in the passive
      samplers studied for the same average velocity over the PUF. The calculated
      sampling rates are in general agreement with those obtained experimentally by
      other researchers.

PMID- 16563583
TI  - Passive air sampling for persistent organic pollutants: introductory remarks to
      the special issue.
AB  - There have been a number of developments in the need, design and use of passive
      air samplers (PAS) for persistent organic pollutants (POPs). This article is the
      first in a Special Issue of the journal to review these developments and some of
      the data arising from them. We explain the need and benefit of developing PAS for
      POPs, the different approaches that can be used, and highlight future
      developments and needs.

PMID- 16563584
TI  - Measurement of trifluralin volatilization in the field: Relation to soil residue
      and effect of soil incorporation.
AB  - Volatilization may represent a major dissipation pathway for pesticides applied
      to soils or crops. A field experiment (September, 2002), consisted in
      volatilization fluxes measurements during 6 days, covering the periods before and
      after soil incorporation carried out 24 h after trifluralin spraying on bare
      soil. Evolution of concentration in soil was measured during 101 days, together
      with soil physical and meteorological variables. Volatilization fluxes were very
      high immediately after application (1900 ng m(-2) s(-1)), decreased down to 100
      ng m(-2) s(-1) in the following 24 h. Soil incorporation strongly abated
      trifluralin concentration in the air. 99% of the total volatilization losses
      recorded over the 6 days following application occurred before incorporation.
      Volatilization fluxes evidenced a diurnal cycle driven by environmental
      conditions. Soil trifluralin residues could still be quantified 101 days after
      application. Our results highlight the caution required when using soil
      degradation half-life values in the field for volatile compounds.

PMID- 16563585
TI  - Probiotics for animal nutrition in the European Union. Regulation and safety
      assessment.
AB  - Probiotics are alive micro-organisms, generally bacteria but also yeasts than,
      when ingested alive in sufficient amount, they have a positive effect on the
      health going beyond the nutritional ones commonly known. Probiotics may operate
      through a nutritional and/or health or sanitary effect. Micro-organisms used in
      animal feed in the EU are mainly bacterial strains of Gram-positive bacteria
      belonging to the types Bacillus, Enterococcus, Lactobacillus, Pediococcus,
      Streptococcus and strains of yeast belonging to the Saccharomyces cerevisiae
      species and kluyveromyces. While most of the species and genera are apparently
      safe, certain micro-organisms may be problematic, particularly the enterococci,
      which may harbour transmissible antibiotic resistance determinants and bacilli,
      specially those belonging to the Bacillus cereus group that are known to produce
      enterotoxins and an emetic toxin. The history and the current legislation in the
      European Union on probiotics feed additives including the requirements for the
      safety assessment for the target animal species, consumers, workers, and
      environment are presented.

PMID- 16563586
TI  - Safety evaluation of a lipase enzyme preparation, expressed in Pichia pastoris,
      intended for use in the degumming of edible vegetable oil.
AB  - BD16449 lipase is the product of a phospholipid-specific lipase gene expressed in
      the yeast Pichia pastoris strain DVSA-PLC-004. This type C phospholipid lipase
      (EC 3.1.4.3) is intended for use in the degumming of edible vegetable oil.
      BD16449 lipase was tested as a refined test article preparation (DV16449) for its
      effects on genotoxicity and in acute, inhalation, and subchronic toxicity
      studies. Dosages ranged from 5000 microg/plate for in vitro toxicity studies to
      2000 mg/kg/day for in vivo toxicity studies. The highest oral dose tested in vivo
      (NOAEL of 2000 mg/kg/day) resulted in a safety margin of 133,000 based on the
      conservative estimate of the total human consumption of BD16449 lipase of 0.015
      mg/kg/day. When adjusted for total organic solids (TOS), the highest oral dose
      tested in vivo (NOAEL of 1680 mg TOS/kg/day) resulted in a safety margin of
      18,300 based on the conservative estimate of the total human consumption of
      BD16449 lipase of 0.092 mg TOS/kg/day [corrected] There was no toxicity reported
      for any of these studies including additional safety studies. A review of the
      literature indicates that P. pastoris fulfills recognized safety criteria
      pertinent to microbial production strains used in the manufacture of food enzyme
      preparations. The results of the toxicity studies presented herein attest to the
      safety of BD16449 lipase for use in the degumming of edible vegetable oil.

PMID- 16563587
TI  - Impact of ciprofloxacin in the human-flora-associated (HFA) rat model: comparison
      with the HFA mouse model.
AB  - The ecological impact of different doses of ciprofloxacin was investigated in an
      experimental germ-free rat model into which human fecal flora was inoculated.
      Animals received oral doses (gavage) of 0, 0.25, 2.5, and 25 mg/kg body weight
      (bw) of ciprofloxacin once daily for 5 weeks. All doses of ciprofloxacin
      significantly reduced aerobic populations. Elimination of Enterobacteriaceae and
      reduction of bifodibacteria were noticed in the group treated with 25 mg/kg of
      the antibiotic. The rest of the intestinal flora was not affected. These effects
      were reversible after the treatment ended. The percentage of resistant
      enterococci increased in rats treated with 2.5 and 25 mg/kg; however, this
      increase was not statistically significant. There was a significant (P < 0.05)
      emergence of ciprofloxacin-resistant Bacteroides fragilis group with 25 mg/kg bw,
      which is equivalent to a human therapeutic dosage of the antibiotic. The MIC
      values and the percentage of resistance remained elevated 2 weeks after the end
      of treatment in this anaerobic population. Although sub-populations of
      enterococci and Enterobacteriaceae showed decreased susceptibility after
      ciprofloxacin administration, resistance was not evident. The ability of an
      exogenous strain of Salmonella to colonize the intestine of animals treated with
      25 mg/kg of ciprofloxacin confirmed that the drug disrupted the colonization
      barrier effect of the indigenous flora at the high dose level tested. No changes
      in the metabolic parameters occurred during the antibiotic treatment. The results
      obtained in the HFA rat model were similar to those obtained in our previous
      study using the HFA mice model where ciprofloxacin at 0.125, 1.25, and 12.5 mg/kg
      bw induced a decrease of enterococci and Enterobacteriaceae populations. The high
      dose of ciprofloxacin also induced a decrease in bifidobacteria counts, an
      increase in levels of resistant B. fragilis group and a significant (P < 0.05)
      disruption of the colonization resistance of the barrier flora in HFA mice.

PMID- 16563588
TI  - What's so special about Asperger Syndrome?

PMID- 16563589
TI  - Human brain evolution and the "Neuroevolutionary Time-depth Principle:"
      Implications for the Reclassification of fear-circuitry-related traits in DSM-V
      and for studying resilience to warzone-related posttraumatic stress disorder.
AB  - The DSM-III, DSM-IV, DSM-IV-TR and ICD-10 have judiciously minimized discussion
      of etiologies to distance clinical psychiatry from Freudian psychoanalysis. With
      this goal mostly achieved, discussion of etiological factors should be
      reintroduced into the Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition (DSM-V). A research agenda for the DSM-V advocated the "development
      of a pathophysiologically based classification system". The author critically
      reviews the neuroevolutionary literature on stress-induced and fear circuitry
      disorders and related amygdala-driven, species-atypical fear behaviors of
      clinical severity in adult humans. Over 30 empirically testable/falsifiable
      predictions are presented. It is noted that in DSM-IV-TR and ICD-10, the
      classification of stress and fear circuitry disorders is neither mode-of
      acquisition-based nor brain-evolution-based. For example, snake phobia (innate)
      and dog phobia (overconsolidational) are clustered together. Similarly, research
      on blood-injection-injury-type-specific phobia clusters two fears different in
      their innateness: 1) an arguably ontogenetic memory-trace-overconsolidation-based
      fear (hospital phobia) and 2) a hardwired (innate) fear of the sight of one's
      blood or a sharp object penetrating one's skin. Genetic architecture-charting of
      fear-circuitry-related traits has been challenging. Various, non-phenotype-based
      architectures can serve as targets for research. In this article, the author will
      propose one such alternative genetic architecture. This article was inspired by
      the following: A) Nesse's "Smoke-Detector Principle", B) the increasing suspicion
      that the "smooth" rather than "lumpy" distribution of complex psychiatric
      phenotypes (including fear-circuitry disorders) may in some cases be accounted
      for by oligogenic (and not necessarily polygenic) transmission, and C) insights
      from the initial sequence of the chimpanzee genome and comparison with the human
      genome by the Chimpanzee Sequencing and Analysis Consortium published in late
      2005. Neuroevolutionary insights relevant to fear circuitry symptoms that
      primarily emerge overconsolidationally (especially Combat related Posttraumatic
      Stress Disorder) are presented. Also introduced is a human-evolution-based
      principle for clustering innate fear traits. The "Neuroevolutionary Time-depth
      Principle" of innate fears proposed in this article may be useful in the
      development of a neuroevolution-based taxonomic re-clustering of stress-triggered
      and fear-circuitry disorders in DSM-V. Four broad clusters of evolved fear
      circuits are proposed based on their time-depths: 1) Mesozoic (mammalian-wide)
      circuits hardwired by wild-type alleles driven to fixation by Mesozoic selective
      sweeps; 2) Cenozoic (simian-wide) circuits relevant to many specific phobias; 3)
      mid Paleolithic and upper Paleolithic (Homo sapiens-specific) circuits (arguably
      resulting mostly from mate-choice-driven stabilizing selection); 4) Neolithic
      circuits (arguably mostly related to stabilizing selection driven by gene-culture
      co-evolution). More importantly, the author presents evolutionary perspectives on
      warzone-related PTSD, Combat-Stress Reaction, Combat-related Stress, Operational
      Stress, and other deployment-stress-induced symptoms. The Neuroevolutionary Time
      depth Principle presented in this article may help explain the dissimilar stress
      resilience levels following different types of acute threat to survival of
      oneself or one's progency (aka DSM-III and DSM-V PTSD Criterion-A events). PTSD
      rates following exposure to lethal inter-group violence (combat, warzone exposure
      or intentionally caused disasters such as terrorism) are usually 5-10 times
      higher than rates following large-scale natural disasters such as forest fires,
      floods, hurricanes, volcanic eruptions, and earthquakes. The author predicts that
      both intentionally-caused large-scale bioevent-disasters, as well as natural
      bioevents such as SARS and avian flu pandemics will be an exception and are
      likely to be followed by PTSD rates approaching those that follow warzone
      exposure. During bioevents, Amygdala-driven and locus-coeruleus-driven epidemic
      pseudosomatic symptoms may be an order of magnitude more common than infection
      caused cytokine-driven symptoms. Implications for the red cross and FEMA are
      discussed. It is also argued that hospital phobia as well as dog phobia, bird
      phobia and bat phobia require re-taxonomization in DSM-V in a new
      "overconsolidational disorders" category anchored around PTSD. The
      overconsolidational spectrum category may be conceptualized as straddling the
      fear circuitry spectrum disorders and the affective spectrum disorders
      categories, and may be a category for which Pitman's secondary prevention
      propranolol regimen may be specifically indicated as a "morning after pill"
      intervention. Predictions are presented regarding obsessive-compulsive disorder
      (OCD) (e.g., female-pattern hoarding vs. male-pattern hoarding) and "culture
      bound" acute anxiety symptoms (taijin-kyofusho, koro, shuk yang, shook yong, suo
      yang, rok-joo, jinjinia-bemar, karoshi, gwarosa, Voodoo death). Also discussed
      are insights relevant to pseudoneurological symptoms and to the forthcoming
      Dissociative-Conversive disorders category in DSM-V, including what the author
      terms fright-triggered acute pseudo-localized symptoms (i.e., pseudoparalysis,
      pseudocerebellar imbalance, psychogenic blindness, pseudoseizures, and epidemic
      sociogenic illness). Speculations based on studies of the human abnormal-spindle
      like, microcephaly-associated (ASPM) gene, the microcephaly primary autosomal
      recessive (MCPH) gene, and the forkhead box p2 (FOXP2) gene are made and
      incorporated into what is termed "The pre-FOXP2 Hypothesis of Blood-Injection
      Injury Phobia." Finally, the author argues for a non-reductionistic fusion of
      "distal (evolutionary) neurobiology" with clinical "proximal neurobiology,"
      utilizing neurological heuristics. It is noted that the value of re-clustering
      fear traits based on behavioral ethology, human-phylogenomics-derived
      endophenotypes and on ontogenomics (gene-environment interactions) can be
      confirmed or disconfirmed using epidemiological or twin studies and psychiatric
      genomics.

PMID- 16563590
TI  - Effects of oral racemic citalopram on neuroendocrine responses.
AB  - Citalopram, a selective serotonin reuptake inhibitor (SSRI), has been used as a
      neuroendocrine probe to assess serotonin (5-HT) function in human subjects. In an
      effort to characterize the oral citalopram challenge, we hypothesized that oral
      racemic citalopram would increase plasma cortisol, prolactin and
      adrenocorticotropic hormone (ACTH) concentrations; ACTH had not been measured in
      previous studies on the neuroendocrine effects of citalopram. Nine healthy male
      subjects initially received 20 mg of citalopram in an open-label study, and
      subsequently received placebo and 40 mg of citalopram in a single-blind,
      randomized, cross-over study. The administration of citalopram 20 mg failed to
      produce a significant neuroendocrine response but 40 mg resulted in reliably
      increased plasma cortisol concentrations. The 40 mg dose, however, did not
      reliably influence the levels of plasma prolactin or plasma ACTH. The results of
      this study indicate that caution should be used in accepting oral racemic
      citalopram as a potential presynaptic serotonergic challenge agent. Further
      studies are needed to fully determine the validity of racemic citalopram and the
      active enantiomer, escitalopram, as 5-HT probes.

PMID- 16563591
TI  - Probabilistic assessment of the cumulative acute exposure to organophosphorus and
      carbamate insecticides in the Brazilian diet.
AB  - In the present study, the cumulative exposure of 25 acetylcholinesterase (AChE)
      inhibiting pesticides through the consumption of nine fruits and vegetables by
      the Brazilian population was assessed. Food consumption data were obtained from a
      household budget survey conducted in all Brazilian states from July 2002 to June
      2003. Residue data from 4001 samples were obtained from the Brazilian national
      monitoring program on pesticide residues. Relative potency factors (RPF) were
      calculated with methamidophos or acephate as index compounds (IC), using BMD(10)
      or NOAEL for AChE inhibition, mostly in rat brain, obtained from national and
      international pesticide evaluations. Monocrotophos and triazophos, in addition to
      aldicarb, had the highest calculated RPF in any scenario. The exposure to AChE
      inhibiting pesticides for the general population at P99.9, represented 33.6% of
      the ARfD as methamidophos and 70.2% ARfD as acephate. The exposure calculated as
      acephate could exceed the ARfD at the upper bound of the 95% confidence interval
      for this percentile. Exposure for children aged up to 6 years were, on average,
      2.4 times higher than the exposure for the general population. Tomato represented
      about 67% of the total intake of AChE inhibiting pesticides. The highest
      calculated equivalent residues in tomato, which drove most of the estimated
      intakes at the high percentiles, were related to the illegal use of monocrotophos
      and triazophos in this crop.

PMID- 16563592
TI  - Tension pneumothorax in asthma.

PMID- 16563593
TI  - Feasibility study of epinephrine administration via laryngeal mask airway using a
      porcine model.
AB  - The laryngeal mask airway (LMA) is gaining wide application as an alternative
      method of maintaining the airway in situations including general anaesthesia, for
      difficult airways and pre-hospital resuscitation. During resuscitation, drug
      administration via an LMA is sometimes warranted when vascular accesses cannot be
      established immediately. Therefore, we conducted a study on the feasibility of
      drug administration via the laryngeal mask airway. Twenty-four pigs were assigned
      into four groups according to the mode of epinephrine (adrenaline)
      administration: intravenous (20 microg/kg; Group 1); tracheal (50 microg/kg;
      Group 2), injection into the upper end of the LMA (50 microg/kg; Group 3), and
      via a catheter through the LMA into the trachea (50 microg/kg; Group 4). Arterial
      blood samples were drawn before and at 2, 4, 6, 8, 10, 12, 14, 16, and 18 min
      after epinephrine administration. Heart rates and arterial blood pressures were
      also recorded at the same time. The peak plasma epinephrine (PPE) levels were
      higher for Group 1 compared to the other groups, with Group 3 producing the
      lowest PPE levels. No significant difference was demonstrated comparing the PPE
      levels for Groups 2 and 4. Further, no differences were noted comparing the mean
      arterial blood pressure and heart rate between these two groups. In this non
      arrest adult porcine model we conclude that epinephrine delivered via a catheter
      passing through the LMA can provide a similar effect as administration via the
      tracheal tube.

PMID- 16563594
TI  - The frequency ratio: an improved method to estimate ventricular fibrillation
      duration based on Fourier analysis of the waveform.
AB  - BACKGROUND: CPR prior to defibrillation improves survival from prolonged
      ventricular fibrillation (VF) by over 10%, based on recent studies. Waveform
      analysis could identify those patients with VF of over 5 to 7-min duration who
      should receive CPR first. A method based on the changes in the Fourier-derived
      frequency spectrum over time could improve the ability to identify prolonged VF.
      METHODS AND RESULTS: The Fourier frequency spectra were calculated on 5-s epochs
      of VF from 45 swine for 12.5 min. The average power at each frequency shows a
      marked loss of frequencies above 8 Hz occurring at 5 min accompanied by an
      increase in the power in frequency spectra from 3 to 5 Hz. A measure termed the
      frequency ratio is defined as the ratio of the power in the high frequency band
      from 8 to 24 Hz compared to the power in the low frequency band from 3 to 5 Hz.
      The frequency ratio is shown to detect 90% of epochs with VF less than 5 min
      while allowing selection of 74% of those epochs over 5 min. When the frequency
      ratio is set to detect 90% of episodes of VF under 7 min, it is able to select
      88% of those traces with VF over 7 min. The receiver operating curve (ROC) for
      the frequency ratio has an area under the curve of 0.91 at 5 min and 0.95 at 7
      min of VF duration. CONCLUSIONS: The frequency ratio is an improved frequency
      based measure of VF duration. Waveform analysis techniques could determine which
      patients should receive shock first and which should receive a period of CPR
      prior to shock, thereby increasing probability of survival.

PMID- 16563595
TI  - Adherence to CPR guidelines during perioperative cardiac arrest in a developing
      country.
AB  - BACKGROUND AND GOAL OF STUDY: Cardiopulmonary resuscitation (CPR) is an integral
      part of anaesthetic training. In Nigeria, these skills are taught mainly during
      medical school and postgraduate training. International guidelines were
      introduced in 2000 and new guidelines were produced in November 2005. The study
      sought to assess how closely anaesthetists in a Nigerian teaching hospital abide
      by the 2000 guidelines. MATERIALS AND METHODS: All perioperative cardiac arrests
      in adults that occurred in a 1-year-period were studied prospectively. All
      patients <15 years and cardiac arrests occurring outside the direct supervision
      of the anaesthetists were excluded. Time and duration of arrest, cardiac arrest
      rhythm and management were documented along with immediate outcome. RESULTS:
      Thirteen cardiac arrests occurred in 2147 perioperative cases (incidence:
      6/1000). Seven patients had non ventricular fibrillation/pulseless ventricular
      tachycardia (VF/VT) rhythms. The mean age of patients was 30.23+/-11.06 years.
      Orotracheal intubation, manual ventilation with 100% O(2) and external chest
      compressions were instituted in all cases. The mean duration of arrest was
      25.66+/-13.34 min. All patients received adrenaline (epinephrine) and atropine.
      The median interval between adrenaline doses was 7.5 min. Only one cycle of
      defibrillation was given to patients in VF/VT. Immediate survival occurred in
      five patients (38.46%). CONCLUSION: Anaesthetists in our hospital are not
      applying proper resuscitation guidelines. The lack of organised simulation
      practice resulted in deficient knowledge and skills. There is a need for
      continuing training in basic and advanced resuscitation for all anaesthetists
      according to the guidelines.

PMID- 16563596
TI  - Performance of department staff in the window between discovery of collapse to
      cardiac arrest team arrival.
AB  - INTRODUCTION: Guideline-directed therapy during the first minutes of
      resuscitation may be life saving. This study assessed the performance of American
      Heart Association (AHA) guidelines by trained departmental staff in the period
      between discovery of collapse and emergency team arrival. METHODS: Over a period
      of 24 months, departmental performance prior to the arrival of the emergency team
      (median 180 s) was assessed by debriefings conducted within 24h of each event in
      a 740-bed tertiary hospital with a dedicated certified resuscitation team.
      Outcome measures were failure to meet AHA treatment recommendations (primary) and
      return of spontaneous circulation (ROSC)/survival to hospital discharge
      (secondary). RESULTS: Two hundred and forty four events were included (216
      patients). Mean age was 69+/-17 years; 45% were women. The underlying causes of
      collapse were mainly cardiac (39%) or respiratory (32%). Residents conducted most
      of the resuscitations (69%) prior to the arrival of the emergency team. Basic
      diagnostic measures such as assessments of pulse and rhythm were not performed in
      19 and 33% of events. Therapeutic measures such as positive pressure ventilation,
      chest compressions and defibrillation were not provided according to the
      guidelines in 17, 12 and 44% of the events. ROSC occurred in 62% of events; 54%
      of VF/VT, 30% of asystole, 22% of PEA and 76% of bradyarrhythmias/severe
      bradycardias. Survival to hospital discharge was 37% overall and 41% for patients
      found in VF/VT (n=33). CONCLUSIONS: Trained departmental staff performed poorly
      in the moments between patient discovery and arrival of the emergency team. Since
      patient outcomes were comparable to those described in the literature, poor
      resuscitation performance may be commonplace in hospitals where ward personnel
      are expected to deliver advanced life support prior to arrival of the emergency
      team.

PMID- 16563597
TI  - A randomized comparison of manual, mechanical and high-impulse chest compression
      in a porcine model of prolonged ventricular fibrillation.
AB  - BACKGROUND: Elevated coronary perfusion pressure (CPP) during CPR is associated
      with return of spontaneous circulation (ROSC). We compared CPP achieved with
      three methods of chest compression: manual (MAN), mechanical (MECH) and high
      impulse mechanical (HI) in a porcine model of prolonged ventricular fibrillation
      (VF). We hypothesized that HI (very rapid acceleration of the down-stroke) would
      produce greater CPPs than MAN or MECH, and that HI would also produce a higher
      rate of ROSC. METHODS: Twenty-eight domestic swine (mean 27.8 kg) were randomly
      assigned to three methods of chest compression. Animals were instrumented under
      anesthesia, and VF was induced and untreated for 8 min. After 2 min of CPR,
      epinephrine (adrenaline) (0. 1 mg/kg), vasopressin (40 U) and propranolol (1.0
      mg) were administered. CPR continued for three more minutes, after which up to
      three rescue shocks were delivered. CPP was determined in an automated fashion by
      measuring the difference between aortic and right atrial pressures 0.1s prior to
      the down-stroke of each compression (i.e. end-relaxation). ROSC was defined as a
      systolic pressure greater than 80 mmHg sustained for at least 1 min. We analyzed
      CPP and ROSC using repeated measures ANOVA and Fisher's exact test. RESULTS: Over
      the 5 min of CPR, CPP increased more with HI compression than with MAN
      compression (p=0.017). ROSC was attained in 4/9 MAN, 6/9 MECH and 10/10 HI (HI
      versus MAN p=0.01). CONCLUSIONS: Over the course of CPR, HI compression increased
      CPP more than MAN compression. HI compression produced a significantly higher
      rate of ROSC than MAN, but not MECH compression.

PMID- 16563598
TI  - Biophysics of cardiopulmonary resuscitation with periodic z-axis acceleration or
      abdominal compression at aortic resonant frequencies.
AB  - Periodic z-axis acceleration (pGz)-CPR involves an oscillating motion of a whole
      patient in the head-to-foot dimension on a mechanized table. The method is able
      to sustain blood flow and long-term survival during and after prolonged cardiac
      arrest in anesthetized pigs. However, the exact mechanism by which circulation of
      blood is created has remained unknown. OBJECTIVES: To explain the hemodynamic
      mechanism of pGz-CPR and to suggest some theoretically useful improvements.
      METHOD: Computer modeling using a hybrid analytical-numerical approach, based
      upon Newton's second law of motion for fluid columns in the aorta and vena cavae,
      Ohm's law for resistive flow through vascular beds, and a 10-compartment
      representation of the adult human circulation. This idealized 70-kg human model
      is exercised to explore the effects upon systemic perfusion pressure of whole
      body z-axis acceleration at frequencies ranging from 0.5 to 5 Hz. The results, in
      turn, suggested studies of abdominal compression at these frequencies. RESULTS
      AND CONCLUSIONS: Blood motion induced in great vessels by periodic z-axis
      acceleration causes systemic perfusion when cardiac valves are competent. Blood
      flow is a function of the frequency of oscillation. At 3.5 Hz, periodic
      acceleration using +/-0.6G and +/-1.2 cm oscillations induces forward blood flow
      of 2.1L/min and systemic perfusion pressure of 47 mmHg. A form of resonance
      occurs at the frequency for peak-flow, in which the period of oscillation matches
      the round-trip transit time for reflected pulse waves in the aorta. For +/-1.0 G
      acceleration at 3.5 Hz, systemic perfusion pressure is 80 mmHg and forward flow
      is 3.8L/min in the adult human model with longitudinal z-axis motion of only +/-2
      cm. Similar results can be obtained using abdominal compression to excite
      resonant pressure-volume waves in the aorta. For 20 mmHg abdominal pressure
      pulses at 3.8 Hz, systemic perfusion pressure is 7 mmHg and forward flow is
      2.8L/min. pGz-CPR and high-frequency abdominal CPR are the physically realistic
      means of generating artificial circulation during cardiac arrest. These
      techniques have fundamental mechanisms and practical features quite different
      from those of conventional CPR and the potential to generate superior systemic
      perfusion.

PMID- 16563599
TI  - Empiric tenecteplase is associated with increased return of spontaneous
      circulation and short term survival in cardiac arrest patients unresponsive to
      standard interventions.
AB  - BACKGROUND: Prospective and retrospective studies have shown that empiric use of
      fibrinolytic agents in sudden cardiac arrest is safe and may improve outcomes in
      sudden cardiac arrest. Use of fibrinolytic agents for this indication is
      increasing in response to these data. METHODS: A prospective multicenter
      observational trial was performed in three emergency departments (EDs) to
      determine the proportion of patients that respond to empiric fibrinolysis with
      tenecteplase (TNK) after failing to respond to Advanced Cardiac Life Support
      (ACLS) measures. Cardiac arrest patients unresponsive to ACLS, who were given TNK
      by their treating physician, were enrolled in an outcome registry. Return of
      spontaneous circulation (ROSC), survival, complications, and neurological
      outcomes were recorded. RESULTS: Fifty patients received TNK after a mean of
      30min of cardiac arrest and eight doses of ACLS medications. One hundred and
      thirteen concurrent control patients received standard ACLS measures. ROSC
      occurred in 26% of TNK patients (95% confidence interval (CI) 16-40%) compared to
      12.4% (95% CI 6.9-20%) among ACLS controls (p=.04); 12% (4.5-24%) of TNK patients
      survived to admission compared to none in the control group (p=.0007); 4% (0.5
      14%) survived to 24h (p=NS); and 4% (0.5-14%) survived to hospital discharge
      (p=NS). All survivors had a good neurological outcome (Cerebral Performance
      Category (CPC) 1-2). One intracranial hemorrhage (ICH) occurred. No other
      significant bleeding complications were observed. CONCLUSIONS: Empiric
      fibrinolysis with TNK in cardiac arrest is associated with increased ROSC and
      short term survival, and with survival to hospital discharge with good
      neurological function in patients who fail to respond to ACLS. Results may
      improve with earlier administration. Prospective controlled interventional trials
      are indicated to evaluate this promising new therapy.

PMID- 16563600
TI  - A public access defibrillation programme in non-inpatient hospital areas.
AB  - INTRODUCTION: Automatic external defibrillators (AED) have proven to be valuable
      and life saving for out of hospital cardiac arrests. Their use in hospital
      arrests is less well documented, but they offer the opportunity to improve
      survival in the hospital setting also. METHODS: The implementation of a public
      access defibrillation (PAD) programme at a tertiary care hospital is described,
      with reference specifically to targeting areas where time from arrest to arrival
      of defibrillation would be greater than 3 min. RESULTS: Nine AEDs were placed in
      areas of the hospital distant from inpatient or outpatient floors. The locations
      of the AEDs were chosen based on a 3 min walk from currently available
      defibrillators to all areas of the hospital, including parking garages and
      walkways from building to building. In this programme AED use in non-inpatient
      hospital locations resulted in the resuscitation of a patient in ventricular
      fibrillation. CONCLUSION: PAD in non-inpatient hospital settings can be life
      saving and similar programmes should be considered for other hospitals.

PMID- 16563601
TI  - Relationship between knowledge of cardiopulmonary resuscitation guidelines and
      performance.
AB  - OBJECTIVE: Despite widespread training with CPR guidelines, CPR is often poorly
      performed. We explore relationships between knowledge of CPR guidelines and
      performance (compression rate, compression depth, compression to ventilation
      ratio, and ventilation volume). METHODS: Sixty professional EMTs were sampled at
      26 randomly ordered EMS response stations from an urban system of 31 stations. A
      recording manikin and video model were used to assess performance in a
      standardized scenario, and a survey was used to assess guideline knowledge.
      Survey and performance outcomes were categorized prospectively as correct or
      incorrect based on the International CPR Guidelines from 2000. Relationships were
      modeled with logistic regression. Covariates included years of work experience,
      frequency of CPR performance, and ALS versus BLS EMT level. RESULTS: Compression
      rate was between 80 and 120 min(-1) in 56% (33/59) of trials. Compression depth
      was 1.5-2 in. in 39% (23/59), compression to ventilation ratio approximated to
      15:2 in 42% (25/59), and ventilation volume was 800-1,200 cm(3) in 13% (8/60).
      Accurate knowledge of the CPR guidelines was associated with better performance
      of chest compression rate and compression to ventilation ratio. Adjusted OR (95%
      CI) were 4.6 (1.2-18.1) for compression rate, 1.7 (0.4-6.5) for compression
      depth, 4.5 (1.1-18.5) for compression to ventilation ratio, and 9.0 (0.2-351) for
      ventilation volume. CONCLUSIONS: Although accurate knowledge of guidelines is
      associated with increased odds of correct performance of some aspects of CPR,
      overall performance remains poor.

PMID- 16563602
TI  - Physician Response Unit -- a feasibility study of an initiative to enhance the
      delivery of pre-hospital emergency medical care.
AB  - OBJECTIVES: To describe the rationale, development and initial results of a
      collaborative pre-hospital pilot project designed to enhance the emergency care
      needs of an inner city population. METHODS: Retrospective descriptive analysis of
      emergency calls attended by a rapid response car staffed by a pre-hospital care
      physician and ambulance service technician or paramedic. RESULTS: Seven hundred
      and forty-eight consecutive patients over a 13-month period are described. Six
      hundred and thirty-eight (82%) patients underwent clinical consultation with a
      physician within 8 min of emergency call. The Physician Response Unit (PRU) also
      provided an additional vehicle responding to emergency calls, reaching the
      national 8 min target response time in 638 (82%) of all cases. Two hundred and
      eighty-nine (39%) of the patients attended had medical therapy initiated by the
      PRU physician. Nearly two-thirds of this group, 189 (65%), received medical
      therapy outside current ambulance service protocols. A physician medical escort
      was provided for 142 (25%) of patients attending hospital. Of all patients seen
      577 (77%) attended the emergency department via ambulance, and 136 (18%) patients
      were assessed, treated and prevented from attending the emergency department.
      CONCLUSIONS: The PRU provided clinical care beyond that delivered by the
      ambulance service. It also contributed positively to local ambulance service
      response times. The service was able to prevent unnecessary ambulance journeys
      and attendance at hospital. It demonstrates that traditional working practices
      can be altered to improve the delivery of emergency medical care.

PMID- 16563604
TI  - Adaptive management and water temperature variability within a South African
      river system: what are the management options?
AB  - Water temperatures, and in particular daily maximum water temperatures, are a
      critical water quality parameter. An understanding of associated resource
      management issues, including links between water temperature variability and
      aquatic diversity values, should be part of any management programme that
      considers river systems. Simple rule-based models have been shown to be
      appropriate tools within an adaptive management approach, both because of their
      heuristic value and in their application for scenario generation. Such a model
      was developed to simulate changes in the condition factor of Chiloglanis anoterus
      [Crass, R.S., 1960. Notes on the freshwater fishes of Natal with descriptions of
      4 new species. Annals of the Natal Museum 14, 405-458] (Pisces: Mochokidae) in
      response to annual frequency of exceedance of a threshold temperature under three
      broad environmental scenarios for part of the Sabie River falling within South
      Africa's Kruger National Park. This model has potential for application within
      the adaptive management programme being implemented by the Kruger National Park.
      Results show that under broad scenarios of a 10% reduction in mean daily flow
      rates, or a 2 degrees C increase in mean daily air temperatures, system
      variability is likely to increase relative to reference conditions . It is
      suggested that so-called "thresholds of probable concern" (TPCs), which are based
      on current levels of "natural" system variability, are useful as management
      targets for achieving a "desired future state" for the river system. The model,
      recognised as a preliminary hypothesis, highlights a lack of knowledge regarding
      the nature of system variability, and the correspondingly wide confidence limits
      of the proposed TPC restricts its utility in a short-term management context.
      Thus, it is now recognised that its value lies more in its use as a long-term
      modelling tool to reflect water temperature responses to flow variability. This
      highlights the fact that research outcomes may not always be those intended at
      the beginning of a project and that opportunities to implement these may be lost
      as lags in understanding relative to project lifetimes often exist.

PMID- 16563603
TI  - Natural terpenes: self-assembly and membrane partitioning.
AB  - Monoterpenes (MTs) are highly hydrophobic substances present in essential oils.
      They cover a wide spectrum of biological effects with a membrane interaction as a
      common point. Here we studied the surface activity of camphor, cineole, thymol,
      menthol and geraniol, and their ability to reach and incorporate into model
      membranes affecting some features of their dynamic organization. All the MTs
      studied self-aggregated in water with critical micellar concentrations (CMC)
      between 3 and 8 microM. Their octanol-water and membrane-water partition
      coefficients were correlated with one another. They all penetrated in
      monomolecular layers of dipalmitoyl-phosphatildylcholine at the air-water
      interface, even at surface pressures (pi) above the equilibrium lateral pressure
      of bilayers; thymol exhibited the highest (61.3 mN/m) and camphor the lowest (37
      mN/m) pi(cut-off) value. They affected the self-aggregation of Triton X-100,
      increasing its CMC from 0.16 mM in the absence of MTs up to 0.68 mM (e.g. for
      geraniol), and the topology of sPC vesicles, increasing its surface curvature,
      suggesting their location at the polar head group region of the membrane. The
      latter was supported by their ability to increase differentially the polarity of
      the membrane environment sensed by two electrochromic dyes. Dipole moment values
      (between 1.224 and 2.523 D) and solvation areas (between 80 and 97 A(2)) were
      calculated from their energy-minimized structures. The relative contribution of
      each experimental, theoretical and structural property to determine MTs' effects
      on membrane dynamics were evaluated by a principal component analysis.

PMID- 16563605
TI  - Characterization of fuel gas products from the treatment of solid waste streams
      with a plasma arc torch.
AB  - This work addresses the plasma treatment of two solid waste streams and
      production of fuel gases from the process. In this study, carpet waste and
      simulated solid wastes generated by a United States Air Force Basic Expeditionary
      Airfield Resources Base deployment were used. Waste was treated in a furnace
      fitted with a 100kW plasma arc torch. The off gas was analyzed to determine its
      composition. The product gas was composed primarily of carbon monoxide and
      hydrogen, with small amounts of methane, benzene and toluene also detected. These
      experiments demonstrate the feasibility of producing fuel gases by plasma
      treatment of the solid waste streams. While the thermal energy value of the fuel
      gas produced in these experiments was less than the energy input, a higher waste
      to-fuel gas conversion efficiency is expected in full-scale application.

PMID- 16563606
TI  - Permeability predictions for sand-clogged Portland cement pervious concrete
      pavement systems.
AB  - Pervious concrete is an alternative paving surface that can be used to reduce the
      nonpoint source pollution effects of stormwater runoff from paved surfaces such
      as roadways and parking lots by allowing some of the rainfall to permeate into
      the ground below. This infiltration rate may be adversely affected by clogging of
      the system, particularly clogging or covering by sand in coastal areas. A
      theoretical relation was developed between the effective permeability of a sand
      clogged pervious concrete block, the permeability of sand, and the porosity of
      the unclogged block. Permeabilities were then measured for Portland cement
      pervious concrete systems fully covered with extra fine sand in a flume using
      simulated rainfalls. The experimental results correlated well with the
      theoretical calculated permeability of the pervious concrete system for pervious
      concrete systems fully covered on the surface with sand. Two different slopes (2%
      and 10%) were used. Rainfall rates were simulated for the combination of direct
      rainfall (passive runoff) and for additional stormwater runoff from adjacent
      areas (active runoff). A typical pervious concrete block will allow water to pass
      through at flow rates greater than 0.2 cm/s and a typical extra fine sand will
      have a permeability of approximately 0.02 cm/s. The limit of the system with
      complete sand coverage resulted in an effective system permeability of
      approximately 0.004 cm/s which is similar to the rainfall intensity of a 30 min
      duration, 100-year frequency event in the southeastern United States. The results
      obtained are important in designing and evaluating pervious concrete as a paving
      surface within watershed management systems for controlling the quantity of
      runoff.

PMID- 16563607
TI  - Type 5 phosphodiesterase inhibitors: curing erectile dysfunction.

PMID- 16563608
TI  - Intra- and peri-operative outcomes comparing radical retropubic and laparoscopic
      radical prostatectomy: results from a prospective, randomised, single-surgeon
      study.
AB  - OBJECTIVES: To prospectively compare intra- and peri-operative outcomes of open
      radical retropubic prostatectomy (RRP) and laparoscopic prostatectomy (LRP) by a
      single surgeon. PATIENTS AND METHODS: One-hundred-twenty, consecutive, age
      matched patients diagnosed with clinically localized prostate cancer were
      eligible for surgery. Sixty patients underwent RRP and 60, LRP. Intra- and peri
      operative parameters, pathologic findings and early complications were recorded.
      A validated visual analogue scale was used to assess pain in the recovery room, 3
      h after the operation and on post-operative days 1, 2 and 3. A cystogram was
      performed on post-operative day 5. RESULTS: Operating time was significantly
      shorter in the RRP group versus the LRP group (mean+/-SD, 170+/-34. 2 vs 235+/
      49.9 min, p<0.001). Blood loss was significantly less in the LRP group versus the
      RRP group (mean+/-SD, 853.3+/-485 vs 257.3+/-177 ml, p<0.001), but no patient in
      either group underwent early re-intervention for bleeding. The RRP group showed a
      trend for higher use of analgesia. A watertight anastomosis was shown at
      cystourethrography and the catheter removed in 86% and 66% of LRP and RRP
      patients, respectively. The overall percentage of post-operative complications
      and positive margins were comparable. CONCLUSION: Laparoscopic prostatectomy is
      an attractive alternative to open prostatectomy, offering the advantages of
      reduced blood loss and safe early catheter removal. Furthermore, the laparoscopic
      procedure proved to be safe oncologically. Long-term follow-up is required to
      compare functional results in terms of continence and potency.

PMID- 16563609
TI  - Left laparoscopic radical nephrectomy with direct access to the renal artery:
      technical advantages.
AB  - OBJECTIVES: To evaluate the technical advantages of early ligature of the renal
      artery at the level of the Treitz ligament during left laparoscopic radical
      nephrectomy (LRN). MATERIAL AND METHODS: Twenty-six patients underwent LRN for
      organ-confined lesions. We grouped measured parameters (see Results) on the basis
      of the first 13 and last 13 patients, and compared both subgroups. All parameters
      were correlated to stage of disease (pT1 vs pT2-3). The Student t test was used
      for statistical analysis. RESULTS: The mean (range) for measured parameters are
      as follows: age: 56.5 +/- 11.6 (41-77) years; American Society of
      Anesthesiologists score: 2.4 +/- 1 (1-3); body mass index: 23.4 +/- 3.4 (21.1
      33); lesion size at computed tomography: (6.2 +/- 2.4 (4-12) cm; operative skin
      to skin time: 130 +/- 20 (125-170) minutes; blood loss: 255 +/- 120 (100-800) ml;
      hospital stay: 6.5 +/- 2.0 (4-15) days; analgesic consumption (Tramadol 100 mg):
      2.5 +/- 1 (2-4) vials; follow-up time: 30.5 +/- 5.6 (3-48) months. No intra
      operative complications occurred. Pathologic analysis showed 12 pT1N0, five
      pT2N0, eight pT3aN0 and one pT3b N2 with mean lesion size of 6.2 +/- 1.6 (4-13)
      cm. Mean number of removed lymph nodes was 9.8 +/- 1.6 (7-17). No statistical
      difference was observed between the two subgroups (p > 0.05), and between pT1 and
      pT2-3 stage (p > 0.05) groups. CONCLUSIONS: Early ligature using direct access to
      the renal artery at the Treitz ligament permits the surgeon to follow the classic
      steps and principles of radical nephrectomy.

PMID- 16563610
TI  - Hypoxia regulation of expression and angiogenic effects of vasoactive intestinal
      peptide (VIP) and VIP receptors in LNCaP prostate cancer cells.
AB  - Vascular endothelial growth factor (VEGF) is a main factor promoting
      neovascularization (angiogenesis) of solid tumours as prostate carcinoma. Hypoxia
      stimulates VEGF gene expression by activating the hypoxia-inducible factor-1 (HIF
      1alpha). In the present study, the hypoxia-mimicking agent Ni(2+) induced
      vasoactive intestinal peptide (VIP) expression at both mRNA and peptide levels
      but it did not modify the expression of VIP receptors (VPAC(1), VPAC(2) and
      PAC(1) receptors) in androgen-dependent human LNCaP prostate cancer cells. VIP
      increased the mRNA levels of VPAC(1) and PAC(1) receptors whereas it decreased
      VPAC(2) receptor mRNA level. These features support that hypoxia up-regulation of
      VIP gene expression in prostatic carcinoma may lead to VIP regulation of the
      expression of its receptors by means of autocrine/paracrine mechanisms. Either
      VIP or hypoxia mimetics with Ni(2+) increased VEGF expression whereas both
      conditions together resulted in an additive response. It suggests two independent
      mechanisms for the observed pro-angiogenic activities of VIP and hypoxia. VIP did
      not stimulate HIF-1alpha mRNA expression but increased the translocation of HIF
      1alpha from the cytosolic compartment to the cell nucleus. Moreover, VIP was
      unable to modify the expression of the HIF-1alpha inhibitor FIH-1 discarding the
      possibility of an indirect effect of VIP on HIF-1 transactivation.

PMID- 16563611
TI  - Characteristics of the Danish families with multiple endocrine neoplasia type 1.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly
      inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations - of
      which 12 are novel - found in 36 Danish families with MEN1 or variant MEN1
      disease. Furthermore, one FIHP family was found to have an earlier reported
      mutation. The mutations were predominantly found in exons 9 and 10 encoding the C
      terminal part of menin. Seven of the mutations were missense mutations, changing
      conserved residues. Furthermore screening of 93 out of 153 consecutive patients
      with primary hyperparathyroidism (pHPT) identified five mutation carriers. Two of
      these belonged to known MEN1 families, whereas the only MEN1-related disease in
      the other three was pHPT. Screening of 96 consecutive patients with fore-/midgut
      endocrine tumours revealed five mutation carries out of 28 patients with sporadic
      gastrinomas, whereas no mutations were found in 68 patients with other fore
      /midgut endocrine tumours. Moreover, screening of 60 consecutive patients with
      primary prolactinoma did not identify any mutation carriers. Our data indicate
      that MEN1 mutation screening is efficient in patients with familial MEN1.
      Screening should also be offered to patients with pHPT or gastrinomas after
      thorough investigation into the family history. In contrast, sporadic carcinoid
      tumours or primary prolactinomas are rarely associated with germ-line MEN1
      mutations.

PMID- 16563612
TI  - Xanthohumol, a prenylflavonoid derived from hops induces apoptosis and inhibits
      NF-kappaB activation in prostate epithelial cells.
AB  - There is increasing evidence that certain natural compounds found in plants may
      be useful as cancer chemopreventive or chemotherapeutic agents. Limited in vitro
      studies indicate that several prenylated flavonoids present in the hop plant
      (Humulus lupulus) possess anticarcinogenic properties. The purpose of this study
      was to investigate the anti-tumorigenic effects of xanthohumol (XN), the major
      prenylflavonoid in hops, on prostate cancer and benign prostate hyperplasia. BPH
      1 and PC3 cell lines were used in our study to represent both non-tumorigenic
      hyperplasia and malignant prostate cancer. In both BPH-1 and PC3 cells, XN and
      its oxidation product, XAL, decreased cell viability in a dose dependent manner
      (2.5-20 microM) as determined by MTT assay and caused an increase in the
      formation of early and late apoptotic cells as determined by Annexin V staining
      and multicaspase assays. XN and its oxygenated derivative also induced cell cycle
      changes in both cells lines, seen in an elevated sub G1 peak at 48h treatment.
      Western blot analysis was performed to confirm the activation of proapoptotic
      proteins, Bax and p53. XN and its derivative caused decreased activation of
      NFkappaB. This work suggests that XN and its oxidation product, XAL, may be
      potentially useful as a chemopreventive agent during prostate hyperplasia and
      prostate carcinogenesis, acting via induction of apoptosis and down-regulation of
      NFkappaB activation in BPH-1 cells.

PMID- 16563613
TI  - Studies on sorption properties of zeolite derived from Indian fly ash.
AB  - Indian fly ash has been completely converted to crystalline porous 13X zeolite by
      NaOH fusion at 600 degrees C followed by hydrothermal treatment at 105 degrees C
      for 20 h. Obtained materials were characterized by XRD, SEM and surface area
      measurement. Prepared material was used for the sorption study of different metal
      ions (Cu(2+), Co(2+) and Ni(2+)) at different pH, temperature. Thermodynamic data
      (DeltaS, DeltaH and DeltaG) corresponding to different metal ion uptake were
      evaluated from Langmuir equation. In all the experiment sorption capacity of
      prepared zeolite was found to be quite high than that of fly ash at acidic pH.
      However, the uptake selectivity order for both the materials is
      Cu(2+)>Co(2+)>Ni(2+).

PMID- 16563614
TI  - Starved air combustion-solidification/stabilization of primary chemical sludge
      from a tannery.
AB  - The high concentration of trivalent chromium along with organic/inorganic
      compounds in tannery sludge causes severe ground water contamination in the case
      of land disposal and chronic air pollution during incineration. In the present
      investigation, the sludge was subjected to flow-through column test to evaluate
      the concentration of leachable organics (tannin, COD and TOC) and heavy metal
      ions (Cr(3+), Fe(2+)) present in it. The dried sludge was incinerated at 800
      degrees C in an incinerator under starved oxygen supply (starved-air combustion)
      to prevent the conversion of Cr(3+) to Cr(6+). The efficiency of starved air
      combustion was studied under different loading rates of sludge. The calcined
      sludge was solidified/stabilized using fly ash and Portland cement/gypsum. The
      solidified bricks were tested for unconfined compressive strength and heavy metal
      leaching. Unconfined compressive strength of the blocks was in the range of 83
      156 kg/cm(2). The stabilization of chromium (III) in the cement gel matrix was
      confirmed with scanning electron microscopy (SEM) and X-ray energy dispersive
      spectroscopy (EDX). Leachability studies on solidified bricks were carried out to
      determine the metal fixation and dissolved organic (as COD) concentration in the
      leachate.

PMID- 16563615
TI  - Preparation of adsorbents made from sewage sludges for adsorption of organic
      materials from wastewater.
AB  - The carbon-bearing adsorbents were prepared from biochemical and surplus sludges
      by physical activation and chemical activation. The results indicated that the
      adsorbents made by way of chemical activation were better, with the optimum
      activator being complex of ZnCl(2) and H(2)SO(4). Moreover, the optimum
      preparation conditions were concentration of two activators 5 mol/L (the ratio of
      ZnCl(2) and H(2)SO(4) was 2:1), at the activating temperature of 550 degrees C,
      in the proportion of solid to liquid 1:2.5, in a period of 2h. Contrasting the
      active carbon, the carbon-bearing adsorbents were characterized by X-ray
      diffraction (XRD), energy dispersive X-ray spectrometer (EDS), scanning electron
      microscope (SEM), BET and BJH. By application of those adsorbents to treatment of
      wastewater of urban, the treatment effect of the carbon-bearing adsorbents were
      better than the active carbon. On the condition that the concentration was 0.5%,
      the COD, P and chromaticity color removal rates of carbon-bearing adsorbent made
      from the biochemical sludge of sewage were higher, which were 79.1, 98.3 and
      87.5%, respectively, and the dynamic adsorption capacity was 47.8 mg/g.

PMID- 16563616
TI  - Treatment of radioactive liquid waste by sorption on natural zeolite in Turkey.
AB  - Liquid radioactive waste has been generated from the use of radioactive materials
      in industrial applications, research and medicine in Turkey. Natural zeolites
      (clinoptilolite) have been studied for the removal of several key radionuclides
      ((137)Cs, (60)Co, (90)Sr and (110m)Ag) from liquid radioactive waste. The aim of
      the present study is to investigate effectiveness of zeolite treatment on
      decontamination factor (DF) in a combined process (chemical precipitation and
      adsorption) at the laboratory tests and scale up to the waste treatment plant. In
      this study, sorption and precipitation techniques were adapted to decontamination
      of liquid low level waste (LLW). Effective decontamination was achieved when
      sorbents are used during the chemical precipitation. Natural zeolite samples were
      taken from different zeolite formations in Turkey. Comparison of the ion-exchange
      properties of zeolite minerals from different formations shows that Gordes
      clinoptilolite was the most suitable natural sorbent for radionuclides under
      dynamic treatment conditions and as an additive for chemical precipitation
      process. Clinoptilolite were shown to have a high selectivity for (137)Cs and
      (110m)Ag as sorbent. In the absence of potassium ions, native clinoptilolite
      removed (60)Co and (90)Sr very effectively from the liquid waste. In the end of
      this liquid waste treatment, decontamination factor was provided as 430 by using
      0.5 mm clinoptilolite at 30 degrees C.

PMID- 16563617
TI  - Kinetic and equilibrium studies on the removal of acid dyes from aqueous
      solutions by adsorption onto activated carbon cloth.
AB  - Removal of acid dyes Acid Blue 45, Acid Blue 92, Acid Blue 120 and Acid Blue 129
      from aqueous solutions by adsorption onto high area activated carbon cloth (ACC)
      was investigated. Kinetics of adsorption was followed by in situ UV-spectroscopy
      and the data were treated according to pseudo-first-order, pseudo-second-order
      and intraparticle diffusion models. It was found that the adsorption process of
      these dyes onto ACC follows the pseudo-second-order model. Adsorption isotherms
      were derived at 25 degrees C on the basis of batch analysis. Isotherm data were
      treated according to Langmuir and Freundlich models. The fits of experimental
      data to these equations were examined.

PMID- 16563618
TI  - Basic dye decomposition kinetics in a photocatalytic slurry reactor.
AB  - Wastewater effluent from textile plants using various dyes is one of the major
      water pollutants to the environment. Traditional chemical, physical and
      biological processes for treating textile dye wastewaters have disadvantages such
      as high cost, energy waste and generating secondary pollution during the
      treatment process. The photocatalytic process using TiO2 semiconductor particles
      under UV light illumination has been shown to be potentially advantageous and
      applicable in the treatment of wastewater pollutants. In this study, the dye
      decomposition kinetics by nano-size TiO2 suspension at natural solution pH was
      experimentally studied by varying the agitation speed (50-200 rpm), TiO2
      suspension concentration (0.25-1.71 g/L), initial dye concentration (10-50 ppm),
      temperature (10-50 degrees C), and UV power intensity (0-96 W). The experimental
      results show the agitation speed, varying from 50 to 200 rpm, has a slight
      influence on the dye decomposition rate and the pH history; the dye decomposition
      rate increases with the TiO2 suspension concentration up to 0.98 g/L, then
      decrease with increasing TiO2 suspension concentration; the initial dye
      decomposition rate increases with the initial dye concentration up to a certain
      value depending upon the temperature, then decreases with increasing initial dye
      concentration; the dye decomposition rate increases with the UV power intensity
      up to 64 W to reach a plateau. Kinetic models have been developed to fit the
      experimental kinetic data well.

PMID- 16563619
TI  - Carbachol injections into the nucleus accumbens induce 50 kHz calls in rats.
AB  - In rats, different types of vocalization can be observed. High frequency
      vocalizations (so called 50 kHz calls) are believed to indicate an appetitive
      state of the emitting animal. This is supported by studies demonstrating that
      infusions of the dopamine agonist amphetamine into the nucleus accumbens (NAC), a
      key structure for appetitive behaviors, induce 50 kHz calls. Several studies
      during the last years demonstrated that not only infusions of dopamine agonists
      such amphetamine but also infusions of acetylcholine receptor agonists into the
      NAC stimulate the appetitive system. In present study, we tested whether
      infusions of the unspecific cholinergic agonist carbachol into the NAC are able
      to induce 50 kHz calls. Indeed, we observed a high number of 50 kHz calls after
      intra-NAC infusions of carbachol. The main frequency of the these calls was
      between 40 and 70 kHz, and the duration was mainly between 10 and 50 ms. We
      hypothesize that acetylcholine transmission within the NAC plays an important
      role in the induction of those ultrasonic calls indicating an appetitive state.

PMID- 16563621
TI  - Association of attention-deficit/hyperactivity disorder with serotonin 4 receptor
      gene polymorphisms in Han Chinese subjects.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is an important public health
      problem. Although serotonin is believed to be an important neurotransmitter in
      the etiology of this disorder, it remains unclear which specific 5-HT receptors
      are involved in regulating the symptoms of ADHD. Previous studies have provided
      favorable evidence for the association of ADHD with both the serotonin
      transporter gene and serotonin 1B receptor gene. To further investigate the role
      of other genes of the serotonergic pathway in ADHD, the current study examined
      variants of the serotonin 4 receptor gene in a relatively large sample of ADHD
      nuclear families. The T allele of the 83097 C>T polymorphism of HTR4 showed a
      tendency of preferential transmission to probands with ADHD (chi(2)=2.699,
      P=0.100). When haplotype TDT analysis of HTR4 was performed, we further found
      that the C/G haplotype of the 83097 C>T and 83198 A>G polymorphisms
      (chi(2)=8.783, P=0.003) and the C/G/C haplotype of these and the -36 C>T
      polymorphism (chi(2)=5.762, P=0.016) were under-transmitted to probands with
      ADHD. These results suggest that the HTR4 gene may play a role in the genetic
      predisposition to ADHD.

PMID- 16563620
TI  - Sexual dimorphism in song-induced ZENK expression in the medial striatum of
      juvenile zebra finches.
AB  - In the brains of male zebra finches (Taeniopygia guttata), the nuclei that direct
      song learning and production are larger than the corresponding regions in
      females, who do not sing. The dimorphism in Area X of the medial striatum (MSt),
      an area important for song learning, is even more dramatic in that it is
      identifiable in males but not females by Nissl stain. In the present study,
      conspecific song, but not other auditory stimuli, induced expression of the
      immediate early gene ZENK in the MSt surrounding but not within Area X in
      juvenile males (30 and 45 days post-hatch). ZENK immunoreactivity following
      conspecific songs was homogeneous throughout the MSt of females at the same ages.
      Little to no FOS immunoreactivity was observed in Area X or the rest of the MSt,
      and levels were not influenced by the type of auditory stimulus presented. Thus,
      the clear morphological difference in the lateral MSt (Area X) of males and
      females is mirrored by a specific functional one, and the data suggest a role for
      ZENK expression in the MSt outside of Area X in responding to relevant song
      stimuli.

PMID- 16563622
TI  - Decreased morphine analgesia in rat overexpressing beta-arrestin 2 at
      periaqueductal gray.
AB  - Beta-arrestin 2 plays important physiological roles in regulating the function of
      the mu opioid receptor (muOR) in vivo. Periaqueductal gray (PAG) is a potential
      structure where morphine produces its antinociception, but it is unclear whether
      beta-arrestin 2 plays its regulatory effect on morphine at PAG. In the present
      study beta-arrestin 2 overexpression was induced by adenovirus at PAG of rats.
      Morphine was administrated in these rats through PAG microinjection and systemic
      administration. The antinociceptive effects of morphine were abolished in rats
      received microinjection of morphine at PAG and partially attenuated in rats
      received systemic administration of morphine. These findings support the notion
      that PAG is an important site where beta-arrestin 2 plays its regulatory effects
      on morphine analgesia.

PMID- 16563623
TI  - Blockade of nicotinic acetylcholine or dopamine D1-like receptors in the central
      nucleus of the amygdala or the bed nucleus of the stria terminalis does not
      precipitate nicotine withdrawal in nicotine-dependent rats.
AB  - Approximately 70% of tobacco smokers wish to quit, but attempts are often
      unsuccessful partly due to the aversive nicotine withdrawal syndrome. We
      investigated the possible involvement of nicotinic and dopaminergic signalling in
      the central nucleus of the amygdala (CeA) and dorsolateral bed nucleus of the
      stria terminalis (dlBNST) in the anhedonic depression-like effect of precipitated
      nicotine withdrawal in rats. Nicotine-dependent rats exhibit elevations in
      intracranial self-stimulation (ICSS) thresholds compared to control rats after
      cessation of chronic nicotine administration (spontaneous withdrawal) or systemic
      or intra-ventral tegmental area (VTA), but not intra-nucleus accumbens (NAcc),
      administration of nicotinic acetylcholine receptor (nAchR) antagonists while
      exposed to nicotine (precipitated withdrawal). We examined whether intracerebral
      administration of the nAChR antagonist dihydro-beta-erythroidine (DHbetaE; 0.6-20
      microg total bilateral dose) or the dopamine D1-like receptor antagonist SCH
      23390 (2-16 microg total bilateral dose) into the CeA and dlBNST results in
      withdrawal-like threshold elevations in nicotine-treated rats. Nicotinic
      acetylcholine and D1-like receptor blockade in the CeA or the dlBNST did not
      induce differential threshold elevations in nicotine- and saline-treated rats.
      Further, the highest SCH 23390 dose (16 microg bilateral dose) injected into the
      dlBNST, but not the CeA, elevated thresholds similarly in both saline- and
      nicotine-treated rats, suggesting that dopaminergic signalling in the dlBNST may
      regulate brain reward function under baseline conditions. These results suggest
      that nACh and D1-like signalling in the CeA and the dlBNST does not develop
      neuroadaptations with the development of nicotine dependence that may be involved
      in the depression-like aspects of nicotine withdrawal.

PMID- 16563624
TI  - Continued disability and pain after lumbar disc surgery: the role of cognitive
      behavioral factors.
AB  - Cognitive-behavioral factors are considered important in the development of
      chronic disability and pain in patients with low back pain. In a prospective
      cohort study of 277 patients undergoing surgery for lumbosacral radicular
      syndrome, the predictive value of preoperatively measured cognitive-behavioral
      factors (fear of movement/(re)injury, passive pain coping, and negative outcome
      expectancies) for disability and pain intensity at 6 weeks and 6 months after
      surgery was investigated, taking into account the effect of possible confounding
      variables. Higher levels of cognitive-behavioral factors were found to be
      associated with a worse outcome at both 6 weeks and 6 months. These associations
      remained significant after controlling for possible confounding variables
      (preoperative disability and pain intensity, age, gender, educational level,
      duration of complaints, neurological deficits, and intake of analgesics) and pain
      intensity 3 days postoperatively. In multiple regression analyses, the cognitive
      behavioral factors independently predicted different outcomes. Fear of
      movement/(re)injury predicted more disability and more severe pain at 6 weeks and
      more severe pain at 6 months; passive pain-coping strategies predicted more
      disability at 6 months; and negative outcome expectancies predicted more
      disability and more severe pain at both 6 weeks and 6 months. The findings
      support the potential utility of preoperative screening measures that include
      cognitive-behavioral factors for predicting surgical outcome, as well as studies
      to examine the potential benefits of cognitive-behavioral treatment to improve
      surgical outcome.

PMID- 16563625
TI  - CB2 cannabinoid receptor mediation of antinociception.
AB  - Management of acute pain remains a significant clinical problem. In preclinical
      studies, CB2 cannabinoid receptor-selective agonists inhibit nociception without
      producing central nervous system side effects. The CB2 receptor-selective agonist
      AM1241 produces antinociceptive effects that are antagonized by CB2, but not CB1,
      receptor-selective antagonists, suggesting that activation of CB2 receptors
      results in antinociception. However, it has not been possible to definitively
      demonstrate that these effects are mediated by CB2 receptors, because we have
      lacked the pharmacological tools to confirm the in vivo receptor selectivity of
      the antagonists used. Further, recent evidence for cannabinoid-like receptors
      beyond CB1 and CB2 raises the possibility that AM1241 exerts its antinociceptive
      effects at uncharacterized CB2-like receptors that are also inhibited by AM630.
      The experiments reported here further test the hypothesis that CB2 receptor
      activation inhibits nociception. They evaluated the antinociceptive actions of
      AM1241 and the less-selective CB2 receptor agonist WIN55,212-2 in wild-type
      (CB2+/+) mice and in mice with genetic disruption of the CB2 receptor (CB2-/-
      mice). AM1241 inhibited thermal nociception in CB2+/+ mice, but had no effect in
      CB2-/- littermates. WIN55,212-2 produced equivalent antinociception in CB1+/+ and
      CB1-/- mice, while its antinociceptive effects were reduced in CB2-/- compared to
      CB2+/+ mice. The effects of morphine were not altered in CB2-/- compared to
      CB2+/+ mice. These data strongly suggest that AM1241 produces antinociception in
      vivo by activating CB2 cannabinoid receptors. Further, they confirm the potential
      therapeutic relevance of CB2 cannabinoid receptors for the treatment of acute
      pain.

PMID- 16563626
TI  - Psychological "resilience" and its correlates in chronic pain: findings from a
      national community sample.
AB  - The display of effective functioning despite exposure to stressful circumstances
      and/or internal distress is often termed 'resilience'. The study of resilience is
      believed to provide information about the nature of illness adaptation that is
      distinct from that obtained via the analysis of clinically impaired groups. In
      recent years, the concept of resilience has seen only limited exploration in the
      chronic pain literature. This article describes a multi-step procedure that first
      identifies resilience among chronic pain sufferers selected from a national
      sample of adults and then examines a set of its psychological correlates. Using
      the Profile of Chronic Pain:Screen (PCP:S), administered to a national sample of
      adults with chronic pain, a resilient subsample was identified on the basis of
      high scores on a Severity scale (at least 1 SD above the mean) combined with low
      scores (at least 1 SD below the mean) on scales assessing Interference and
      Emotional Burden. An age- and gender-matched non-resilient subsample was then
      selected who scored high (at least one standard deviation above the mean) on
      Severity, Interference, and Emotional Burden. The results of a series of
      comparisons between the resilient and non-resilient groups revealed significant
      differences favoring resilient individuals in coping style, pain attitudes and
      beliefs, catastrophizing tendencies, positive and negative social responses to
      pain, and health care and medication utilization patterns. The findings provide a
      preliminary foundation for further research aimed at understanding the nature and
      causal underpinnings of resilience in persons with chronic pain.

PMID- 16563627
TI  - Analysis of synchrony demonstrates 'pain networks' defined by rapidly switching,
      task-specific, functional connectivity between pain-related cortical structures.
AB  - Imaging studies indicate that experimental pain is processed in multiple cortical
      areas which are often characterized as a network. However, the functional
      connectivity within the network and the other properties of the network is poorly
      understood. Substantial evidence demonstrates that synchronous oscillations
      between two cortical areas may indicate functional connectivity between those
      areas. We test the hypothesis that cortical areas with pain-related activity are
      functionally connected during attention to a painful stimulus. We stimulated with
      a painful, cutaneous, laser stimulus and recorded the response directly from the
      cortical surface (electrocorticography--ECoG) over primary somatosensory (SI),
      parasylvian (PS), and medial frontal (MF) cortex through subdural electrodes
      implanted for treatment of epilepsy. The results demonstrate synchrony of ECoGs
      between cortical structures receiving input from nociceptors, as indicated by the
      occurrence of laser-evoked potentials (LEPs) and/or event-related
      desynchronization (ERD). Prior to the stimulus, directed attention to the painful
      stimulus consistently increased the degree of synchrony between SI and PS
      regions, as the subject anticipated the stimulus. After the laser stimulus,
      directed attention to the painful stimulus consistently increased the degree of
      synchrony between SI and MF cortex, as the subject responded by counting the
      stimulus. Therefore, attention to painful stimuli always enhanced synchrony
      between cortical pain-related structures. The pattern of this synchrony changed
      as the patient switched tasks from anticipation of the stimulus to counting the
      stimulus. These results are the first compelling evidence of pain networks
      characterized by rapidly switching, task-specific functional connectivity.

PMID- 16563628
TI  - Chronic pain couples: perceived marital interactions and pain behaviours.
AB  - Patient adjustment to chronic pain is well known to be influenced by the spouse
      and his or her response to patient expressions of pain. However, these responses
      do not occur in a vacuum, and the aim of the present study was to investigate
      patient-spouse interactions in chronic pain in detail. Ninety-five patient-spouse
      dyads completed questionnaires relating to mood, marital satisfaction and
      communication, and 80 couples also took part in semi-structured interviews. Data
      were analysed using quantitative and qualitative methods. Results showed that
      spouses of chronic pain patients reported engaging in a far wider repertoire of
      responses to pain behaviours than has been recognised to date. New response
      categories of 'hostile-solicitous' and 'observe only' were identified. Patients
      generally interpreted solicitous responses less favourably than spouse responses
      which encouraged task persistence. Male spouses identified fewer pain-related
      situations than female spouses but were more likely to report responding
      solicitously to patient pain behaviours. Marital satisfaction was significantly
      higher in patients who rated themselves as talking more frequently about their
      pain. Spouse perceived frequency of pain talk was not related to spouse marital
      satisfaction. There were no gender differences in marital satisfaction. The
      results of this study challenge some of the assumptions that have been held
      regarding chronic pain patient-spouse interactions.

PMID- 16563629
TI  - Orofacial cold hyperalgesia due to infraorbital nerve constriction injury in
      rats: reversal by endothelin receptor antagonists but not non-steroidal anti
      inflammatory drugs.
AB  - The susceptibility of changes in responsiveness to noxious cold stimulation of
      rats submitted to chronic constriction of the infraorbital nerve (CION) or
      carrageenan to drug inhibition was compared. Nocifensive responses were measured
      as total time rats engaged in bilateral facial grooming with both forepaws over
      the first 2 min following tetrafluoroethane spray application to the snout.
      Carrageenan (50 microg, s.c. into upper lip) caused short-lived ipsilateral cold
      hyperalgesia (peak at 3 h: vehicle 8.4+/-1.3, carrageenan 21.2+/-3.0 s) which was
      markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10mg/kg) or s.c.
      dexamethasone (0.5 mg/kg), endothelin ET(A) or ET(B) receptor antagonists (BQ-123
      and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia
      between Days 2 and 12, which peaked on Days 4 (sham 15.3+/-1.8, CION 32.4+/-5.3s)
      to 6. Established peak CION-induced cold hyperalgesia was unaffected by
      indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v.
      injections of selective antagonists of ET(A) (atrasentan, 3-10 mg/kg) or ET(B) (A
      192621, 5-20 mg/kg) receptors caused significant inhibitions lasting 1-2.5h
      (peaks approximately 65-90%). Bosentan (dual ET(A)/ET(B) receptor antagonist, 10
      mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6h. Thus, once
      established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack
      an inflammatory component, but is alleviated by endothelin ET(A) and/or ET(B)
      receptor antagonists. If this CION injury model bears predictive value to
      trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various
      stimuli), endothelin receptors might constitute new targets for treatment of this
      disorder.

PMID- 16563630
TI  - Catastrophic thinking and heightened perception of pain in others.
AB  - Past research has shown that pain catastrophizing contributes to heightened pain
      experience. The hypothesis advanced in this study was that individuals who score
      high on measures of pain catastrophizing would also perceive more intense pain in
      others. The study also examined the role of pain behaviour as a determinant of
      the relation between catastrophizing and estimates of others' pain. To test the
      hypothesis, 60 undergraduates were asked to view videotapes of individuals taking
      part in a cold pressor procedure. Each individual in the videotapes was shown
      three times over the course of a 1min immersion such that the same individual was
      observed experiencing different levels of pain. Correlational analyses revealed a
      significant positive correlation between levels of pain catastrophizing and
      inferred pain intensity, r=.31, p<.01. Follow-up analyses indicated that
      catastrophizing was associated with a heightened propensity to rely on pain
      behaviour as a basis for drawing inferences about others' pain experience.
      Catastrophizing was associated with more accurate pain inferences on only one of
      three indices of inferential accuracy. The pattern of findings suggests that
      increasing reliance on pain behaviour as a means of inferring others' pain will
      not necessarily yield more accurate estimates. Discussion addresses the processes
      that might underlie the propensity to attend more to others' pain behaviour, and
      the clinical and interpersonal consequences of perceiving more pain in others.

PMID- 16563631
TI  - Immune response to Sarcocystis neurona infection in naturally infected horses
      with equine protozoal myeloencephalitis.
AB  - Equine protozoal myeloencephalitis (EPM) is one of the most common neurologic
      diseases of horses in the United States. The primary etiologic agent is
      Sarcocystis neurona. Currently, there is limited knowledge regarding the
      protective or pathophysiologic immune response to S. neurona infection or the
      subsequent development of EPM. The objectives of this study were to determine
      whether S. neurona infected horses with clinical signs of EPM had altered or
      suppressed immune responses compared to neurologically normal horses and if blood
      sample storage would influence these findings. Twenty clinically normal horses
      and 22 horses with EPM, diagnosed by the presence of S. neurona specific
      antibodies in the serum and/or cerebrospinal (CSF) and clinical signs, were
      evaluated for differences in the immune cell subsets and function. Our results
      demonstrated that naturally infected horses had significantly (P<0.05) higher
      percentages of CD4 T-lymphocytes and neutrophils (PMN) in separated peripheral
      blood leukocytes than clinically normal horses. Leukocytes from naturally
      infected EPM horses had significantly lower proliferation responses, as measured
      by thymidine incorporation, to a non-antigen specific mitogen than did clinically
      normal horses (P<0.05). Currently, studies are in progress to determine the role
      of CD4 T cells in disease and protection against S. neurona in horses, as well as
      to determine the mechanism associated with suppressed in vitro proliferation
      responses. Finally, overnight storage of blood samples appears to alter T
      lymphocyte phenotypes and viability among leukocytes.

PMID- 16563632
TI  - Control of gastrointestinal nematodes in goats on pastures in South Africa using
      nematophagous fungi Duddingtonia flagrans and selective anthelmintic treatments.
AB  - The effectiveness of selective anthelmintic treatments and use of nematophagous
      fungi Duddingtonia flagrans in reducing levels of gastrointestinal nematodes in
      goats was investigated at Onderstepoort, South Africa. Nineteen (19) naturally
      infected indigenous male goats, aged 10 months, were separated into four groups
      and grazed in separate previously ungrazed paddocks for two worm seasons
      (February 2002-March 2003). Two groups of goats were fed D. flagrans
      chlamydospores daily and two groups did not receive fungi. The FAMACHA system was
      used to determine which goats required anthelmintic treatments. Twice as many
      goats in the no-fungi fed group required treatments as compared with the fungi
      fed group. Mean FAMACHA scores in the no-fungi fed group were higher during most
      of the sampling occasions compared to the group fed fungi, but the difference was
      not significant. The group-mean faecal egg counts and PCV% were comparable
      between the two treatment groups throughout the study. Haemonchus was the
      predominant parasite genus in composite group faecal cultures. Group-mean body
      weights and body condition scores were higher for the no-fungi fed group from May
      2002 up to the end of the study, though statistical differences were not
      significant. Mean worm burdens indicated that the most abundant species infecting
      animals were Haemonchus contortus and Trichostrongylus spp. and were higher in
      the fungi fed group. More animals required individual anthelmintic treatments in
      the no-fungi fed group. The requirement for extra treatments in the no-fungi fed
      group must, however, be considered against the financial cost of the fungi, the
      requirement of daily feeding of the fungi, the lower performance and higher worm
      burdens in the fungi fed group.

PMID- 16563633
TI  - Catalase-peroxidase of Mycobacterium bovis BCG converts isoniazid to
      isonicotinamide, but not to isonicotinic acid: differentiation parameter between
      enzymes of Mycobacterium bovis BCG and Mycobacterium tuberculosis.
AB  - Isonicotinic acid hydrazide (Isoniazid, INH) is one of the major drugs worldwide
      used in the chemotherapy of tuberculosis. Many investigators have emphasized that
      INH activation is associated with mycobacterial catalase-peroxidase (katG).
      However, INH activation mechanism is not completely understood. In this study,
      katG of M. bovis BCG was separated and purified into two katGs, katG I (named as
      relatively higher molecular weight than katG II) and katG II, indicating that
      there is some difference in protein structure between two katGs. The molecular
      weight of the enzymes of katG I and katG II was estimated to be approximately
      150,000 Da by gel filtration, and its subunit was 75,000 Da as determined by SDS
      PAGE, indicating that purified enzyme was composed of two identical subunits. The
      specific activity of the purified enzyme katG I was 991.1 (units/mg). The enzymes
      were then investigated in INH activation by using gas chromatography mass
      spectrometry (GC-MS). The analysis of GC-MS showed that the katG I from M. bovis
      BCG directly converted INH (Mr, 137) to isonicotinamide (Mr, 122), not to
      isonicotinic acid (Mr, 123), in the presence or absence of H2O2. Therefore, this
      is the first report that katG I, one of two katGs with almost same molecular
      weight existed in M. bovis BCG, converts INH to isonicotinamide and this study
      may give us important new light on the activation mechanism of INH by KatG
      between M. bovis BCG and M. tuberculosis.

PMID- 16563634
TI  - Modulation of polyene antibiotics self-association by ions from the Hofmeister
      series.
AB  - The toxicity of the antifungal polyene antibiotic amphotericin B (AMB) has been
      related to its low solubility, more specifically to a self-associated form termed
      toxic aggregate. In addition, AMB in aqueous medium gives rise to concentration,
      ionic strength, and time-dependent polydisperse systems. For this reason
      different approaches, including the use of several lipid aggregates, have been
      used in attempts to improve the drug's solubility and increase its therapeutic
      index. In this context, understanding AMB's self-association properties should
      help in the preparation of less toxic formulations. Ions from the Hofmeister
      series alter water properties: while kosmotropes (water structure makers-sulfate,
      citrate, phosphate) decrease solute solubility, chaotropes (water structure
      breakers-perchlorate, thiocyanate, trichloroacetate, and the neutral molecule
      urea) have opposite effects. This work reports a study of the effect of
      Hofmeister ions and urea on the self-aggregation of AMB and some of its
      derivatives. Optical absorption and circular dichroism spectra were used to
      monitor monomeric and aggregated antibiotic. While kosmotropes increased
      aggregation in a concentration-dependent manner, the opposite was observed for
      chaotropes. It is shown, for the first time, that thiocyanate and
      trichloroacetate can induce complete AMB monomerization. The understanding of
      these processes at the physicochemical and molecular levels and the possibility
      of modulating the aggregation state of AMB and its derivatives should contribute
      to elucidate the mechanisms of action and toxicity of this widely used antibiotic
      and to develop more efficient and less toxic preparations.

PMID- 16563635
TI  - Pro-apoptotic role of NF-kappaB: implications for cancer therapy.
AB  - Nuclear factor-kappaB (NF-kappaB) is generally viewed as anti-apoptotic and
      oncogenic, leading to a quest for its inhibitors. However, recent evidence
      suggests that in some situations NF-kappaB may promote apoptosis. Depending on
      the specific cell type and the stimulus involved, NF-kappaB activation may lead
      to either anti- or pro-apoptotic response. Both these effects can be mediated by
      NF-kappaB in a context-dependent manner by selectively regulating its target
      genes. In this review, we discuss the evidence for NF-kappaB's pro-apoptotic role
      and explore the possible mechanisms behind it. We emphasize that rather than
      trying to inhibit NF-kappaB in cancer therapy, agents should be developed to
      unleash its pro-apoptotic ability.

PMID- 16563636
TI  - The current status of FDG-PET in tumour volume definition in radiotherapy
      treatment planning.
AB  - Positron emission tomography (PET) scan, mainly using 18 F-fluoro-deoxyglucose
      (FDG) as a tracer, is currently widely accepted as a diagnostic tool in oncology.
      It may lead to a change in staging and therefore in treatment management. PET can
      also be used to define the target volume in radiation treatment planning and to
      evaluate treatment response. In this review, we focused on issues concerning the
      role of PET in target volume delineation, both for the primary tumour and
      regional lymph nodes. A literature search was performed using MEDLINE.
      Furthermore, the following questions were addressed: does PET allow accurate
      tumour delineation and does it improve the outcome of radiotherapy, in terms of
      reduced toxicity or a higher tumour control probability? Combined computer
      tomography (CT) and PET information seems to influence target volume delineation.
      Using (CT-) PET scan, interobserver variability is being reduced. Only few
      studies compared delineation based on PET with pathologic examination, showing a
      complex relation. Preliminary results concerning incorporation of PET information
      in to target volume delineation varies in different tumour sites. In the field of
      lung cancer, incorporation of PET seems to improve tumour coverage and spare
      normal tissues, which may lead to less toxicity or the possibility to escalate
      dose. In oesophageal cancer and in lymphoma, PET scan can be used to include PET
      positive lymph nodes in the target volume. In most other tumour sites not enough
      data are currently available to draw definitive conclusions about the role of PET
      in radiation treatment planning.

PMID- 16563637
TI  - Brain projections from the medullary dorsal reticular nucleus: an anterograde and
      retrograde tracing study in the rat.
AB  - In the last 15 years a role has been ascribed for the medullary dorsal reticular
      nucleus as a supraspinal pain modulating area. The medullary dorsal reticular
      nucleus is reciprocally connected with the spinal dorsal horn, is populated
      mainly by nociceptive neurons and regulates spinal nociceptive processing. Here
      we analyze the distribution of brain projections from the medullary dorsal
      reticular nucleus using the iontophoretic administration of the anterograde
      tracer biotinylated-dextran amine and the retrograde tracer cholera toxin subunit
      B. Fibers and terminal boutons labeled from the medullary dorsal reticular
      nucleus were located predominately in the brainstem, although extending also to
      the forebrain. In the medulla oblongata, anterograde labeling was observed in the
      orofacial motor nuclei, inferior olive, caudal ventrolateral medulla, rostral
      ventromedial medulla, nucleus tractus solitarius and most of the reticular
      formation. Labeling at the pons-cerebellum level was present in the locus
      coeruleus, A5 and A7 noradrenergic cell groups, parabrachial and deep cerebellar
      nuclei, whereas in the mesencephalon it was located in the periaqueductal gray
      matter, deep mesencephalic, oculomotor and anterior pretectal nuclei, and
      substantia nigra. In the diencephalon, fibers and terminal boutons were found
      mainly in the parafascicular, ventromedial, and posterior thalamic nuclei and in
      the arcuate, lateral, posterior, peri- and paraventricular hypothalamic areas.
      Telencephalic labeling was consistent but less intense and concentrated in the
      septal nuclei, globus pallidus and amygdala. The well-known role of the medullary
      dorsal reticular nucleus in nociception and its pattern of brain projections in
      rats suggests that the nucleus is possibly implicated in the modulation of: (i)
      the ascending nociceptive transmission involved in the motivational-affective
      dimension of pain; (ii) the endogenous supraspinal pain control system centered
      in the periaqueductal gray matter-rostral ventromedial medulla-spinal cord
      circuitry; (iii) the motor reactions associated with pain.

PMID- 16563638
TI  - Analysis of behavior-related excitatory inputs to a central pacemaker nucleus in
      a weakly electric fish.
AB  - Gymnotid electric fish explore their environment and communicate with
      conspecifics by means of rhythmic electric organ discharges. The neural command
      for each electric organ discharge arises from activity of a medullary pacemaker
      nucleus composed of two neuronal types: pacemaker and relay cells. During
      different behaviors as in courtship, exploration and agonistic interactions,
      these species display specific electric organ discharge frequency and/or waveform
      modulations. The neural bases of these modulations have been explained in terms
      of segregation of inputs to pacemaker or relay cells, as well as differential
      activation of the glutamate receptors of these cells. One of the most conspicuous
      electric organ discharge frequency modulations in Gymnotus carapo results from
      the activation of Mauthner cells, a pair of reticulospinal neurons that are
      involved in the organization of sensory-evoked escape responses in teleost fish.
      The activation of Mauthner cells in these animals produces a prolonged increase
      in electric organ discharge rate, whose neural mechanisms involves the activation
      of both N-methyl-D-aspartate (NMDA) and metabotropic glutamatergic receptors of
      pacemaker cells. Here we provide evidence which indicates that pacemaker cells
      are the only cellular target of the synaptic inputs responsible for the Mauthner
      cell initiated electric organ discharge modulation at the medullary pacemaker
      nucleus. Additionally, although pacemaker cells express both NMDA and non-NMDA
      ionotropic receptors, we found that non-NMDA receptors are not involved in this
      synaptic action which suggests that NMDA and non-NMDA receptor subtypes are not
      co-localized at the subsynaptic membrane. NMDA receptor activation of pacemaker
      cells seems to be an efficient neural strategy to produce long-lasting
      enhancements of the fish sampling capability during Mauthner cell-initiated motor
      behaviors.

PMID- 16563639
TI  - Neuroprotection of rat hippocampal slices exposed to oxygen-glucose deprivation
      by enrichment with docosahexaenoic acid and by inhibition of hydrolysis of
      docosahexaenoic acid-containing phospholipids by calcium independent
      phospholipase A2.
AB  - Polyunsaturated fatty acids play an important role in the development of
      pathological states in brain after hypoxia/ischemia. Here, we investigated the
      role of docosahexaenoic acid (22:6n-3) in brain phospholipids for neuronal
      survival. We used organotypic cultures of rat brain hippocampal slices exposed to
      40 min of oxygen-glucose deprivation, to study the consequences of experimental
      ischemia. In [14C]docosahexaenoic acid-labeled cultures, oxygen-glucose
      deprivation induced significant release of radioactive docosahexaenoic acid. This
      release could be blocked by the selective inhibitor of the Ca2+-independent
      phospholipase A2, 4-bromoenol lactone (10 microM), when it was added 30 min prior
      to oxygen-glucose deprivation. Addition of 4-bromoenol lactone at 30 min prior to
      oxygen-glucose deprivation markedly decreased the neuronal damage induced by
      oxygen-glucose deprivation. The protective effect was substantially higher in
      dentate gyrus than in CA1 and CA3 areas. Enrichment of the hippocampal tissue
      with docosahexaenoic acid by incubation with 10 microM docosahexaenoic acid for
      24 h exerted the same neuroprotective effect, which was observed after treatment
      with 4-bromoenol lactone. In contrast to the 24 h-preincubation, simultaneous
      addition of docosahexaenoic acid with the onset of oxygen-glucose deprivation had
      no protective effect. This suggests that incorporation of docosahexaenoic acid
      into phospholipids is required for the protective effect observed. Then the
      possible involvement of arachidonic acid metabolism in docosahexaenoic acid
      induced neuroprotection was tested. Inhibition of prostaglandin production by
      ibuprofen produced no change in neuroprotection after 24-h incubation of the
      hippocampal slices with docosahexaenoic acid. Simultaneous inhibition of Ca2+
      independent and Ca2+-dependent phospholipases A2 by treatment with the general
      phospholipase A2 inhibitor methyl arachidonyl fluorophosphonate (3 microM, 30 min
      prior to oxygen-glucose deprivation) resulted in significant enhancement of the
      neuroprotective effect in the dentate gyrus, but not in the CA1 and CA3 areas. In
      summary, the results reported here indicate that docosahexaenoic acid and
      docosahexaenoic acid-containing phospholipids provide potent protection against
      neurodegeneration after hypoxia/hypoglycemia. Furthermore, our data suggest that
      Ca2+-independent phospholipase A2, the isoform, which has been largely ignored so
      far, is a possible target for treatment of ischemia-related pathologies in brain.

PMID- 16563640
TI  - Nuclear organization and dynamics of transcription sites in rat sensory ganglia
      neurons detected by incorporation of 5'-fluorouridine into nascent RNA.
AB  - In this study we have used the transcription assay with 5'-fluorouridine
      incorporation into nascent RNA to analyze the nuclear organization and dynamics
      of transcription sites in rat trigeminal ganglia neurons. The 5'-FU administrated
      by i.p. injection was successfully incorporated into nuclear domains containing
      actively transcribing genes of trigeminal neurons. 5'-Fluorouridine RNA-labeling
      was detected with immunocytochemistry at light and electron microscopy levels.
      The 5'-fluorouridine incorporation sites were detected in the nucleolus,
      particularly on the dense fibrillar component, and in numerous transcription foci
      spread throughout the euchromatin regions, without preferential positioning at
      the nuclear periphery or in the nuclear interior. Double labeling experiments to
      combine 5'-fluorouridine incorporation with molecular markers of nuclear
      compartments showed the absence of transcription sites in Cajal bodies and
      nuclear speckles of splicing factors. Similarly, no 5'-fluorouridine labeling was
      detected in well-characterized chromatin silencing domain, the telomeric
      heterochromatin. The specificity and sensitivity of the run-on transcription
      assay in trigeminal ganglia neurons was verified by the i.p. administration of
      the transcription inhibitor actinomycin D. The dramatic reduction in RNA
      synthesis upon actinomycin D treatment was associated with two important cellular
      events, heterochromatin silencing and formation of DNA damage/repair nuclear
      foci, demonstrated by the expression of tri-methylated histone H4 and
      phosphorylated H2AX, respectively. 5'-Fluorouridine incorporation in animal
      models provides a useful tool to investigate the organization of gene expression
      in mammalian neurons in both normal physiology and experimental pathology
      systems.

PMID- 16563641
TI  - Effect of eugenol on spreading depression and epileptiform discharges in rat
      neocortical and hippocampal tissues.
AB  - Eugenol, an aromatic molecule derived from several plants, has been receiving
      examination for clinical relevance in epilepsy and headache. To investigate the
      neurophysiologic properties of the action of eugenol, its effects on epileptiform
      field potentials elicited by omission of extracellular Mg2+, spreading depression
      induced by KCl microinjection, electrically evoked field potentials, and long
      term potentiation were tested in rat neocortical and hippocampal tissues. Eugenol
      (10-100 micromol/l) dose-dependently and reversibly suppressed both epileptiform
      field potentials and spreading depression Eugenol also reversibly decreased the
      amplitude of the field postsynaptic potentials evoked in CA1 area of hippocampus
      and the third layer of neocortex. Eugenol significantly reduced the long-term
      potentiation by approximately 30% compared with controls. Thus, eugenol can
      suppress epileptiform field potentials and spreading depression, likely via
      inhibition of synaptic plasticity. The results indicate the potential for eugenol
      to use in the treatment of epilepsy and cephalic pain.

PMID- 16563642
TI  - Characterization of CB1 cannabinoid receptor immunoreactivity in postmortem human
      brain homogenates.
AB  - The CB1 cannabinoid receptor (CB1) is the predominant type of cannabinoid
      receptor in the CNS, in which it displays a unique anatomical distribution and is
      present at higher densities than most other known seven transmembrane domain
      receptors. Nevertheless, as with almost all seven transmembrane domain receptors,
      the tertiary and quaternary structure of this receptor is still unknown. Studies
      of CB1 in rat cerebral tissue are scarce, and even less is known regarding the
      expression of CB1 in the human brain. Thus, the aim of the present work was to
      characterize CB1 expression in membranes from postmortem human brain using
      specific antisera raised against this protein. Western blot analysis of P1 and P2
      fractions, and crude plasma membrane preparations from the prefrontal cortex
      showed that CB1 migrated as a 60 kDa monomer under reducing conditions. These
      data were confirmed by blotting experiments carried out with human U373MG
      astrocytoma cells as a positive control for CB1 expression and wild-type CHO
      cells as negative control. In addition, when proteins were solubilized in the
      absence of dithiothreitol, the anti-human CB1 antiserum detected a new band
      migrating at around 120 kDa corresponding in size to a putative CB1 dimer. This
      band was sensitive to reducing agents (50 mM dithiothreitol) and showed sodium
      dodecylsulphate stability, suggesting the existence of disulfide-linked CB1
      dimers in the membrane preparations. Important differences in the anatomical
      distribution of CB1 were observed with regard to that described previously in
      monkey and rat; in the human brain, CB1 levels were higher in cortex and caudate
      than in the cerebellum.

PMID- 16563643
TI  - Free radical-mediated neurotoxicity may be caused by inhibition of mitochondrial
      dehydrogenases in vitro and in vivo.
AB  - We previously demonstrated that copper facilitated the formation of reactive
      oxygen species, and inhibited pyruvate dehydrogenase and alpha-ketoglutarate
      dehydrogenase in vitro and in animal models of Wilson's disease in vivo. However,
      direct Cu(2+) toxicity has only been demonstrated for Wilson's disease. We now
      hypothesize that inhibition of these mitochondrial dehydrogenases might also
      contribute to many other injuries and disorders that are reactive oxygen species
      mediated. We have modeled reactive oxygen species-mediated injuries using
      inducers of reactive oxygen species such as hydrogen peroxide, ethacrynic acid or
      menadione, or another redox active metal (Cd(2+)). Here we demonstrated that
      these toxic exposures were accompanied by an early marked reduction in both
      pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase activities, followed
      by a decrease in neuronal mitochondrial transmembrane potential and ATP, prior to
      murine cortical neuronal death. Thiamine (6 mM), and dihydrolipoic acid (50
      microM), required cofactors for pyruvate dehydrogenase and alpha-ketoglutarate
      dehydrogenase (thiamine as thiamine pyrophosphate), attenuated the reactive
      oxygen species-induced reductions in these enzyme activities, as well as
      subsequent loss of mitochondrial transmembrane potential and ATP, and neuronal
      death. We next tested the effect of thiamine supplementation on an in vivo model
      of reactive oxygen species-mediated injury, transient middle cerebral artery
      occlusion, and reperfusion in rats. Oral or i.p. thiamine administration reduced
      the middle cerebral artery occlusion-induced infarct. These data suggest that
      reactive oxygen species-induced neuronal death may be caused in part by reactive
      oxygen species-mediated inhibition of pyruvate dehydrogenase and alpha
      ketoglutarate dehydrogenase in vitro and in vivo, and that thiamine or
      dihydrolipoic acid may constitute potential therapeutic agents not just against
      Cu(2+) neurotoxicity, but may reduce neuronal degeneration in the broader range
      of diseases mediated by free radical stress.

PMID- 16563644
TI  - The influence of difficult temperament on alcohol-related aggression: better
      accounted for by executive functioning?
AB  - The purpose of this investigation was to test the hypothesis that executive
      functioning (EF) would mediate the relation between difficult temperament (DT)
      and intoxicated aggression. Participants were 165 social drinking men and women
      between the ages of 21-35years old. DT was measured using the Dimension of
      Temperament Scale - Revised and EF was measured using seven well-established
      neuropsychological tests. Following consumption of an alcoholic beverage,
      participants were tested on a laboratory aggression measure in which electric
      shocks were received from and administered to a fictitious opponent under the
      guise of a competitive reaction time task. Aggression was operationalized as
      shock intensities administered to the fictitious opponent under conditions of low
      and high provocation. Results indicated that EF successfully mediated the
      relation between DT and intoxicated aggression for men but not for women. These
      findings are discussed with regard to how they influence current models of
      aggressive behavior as well as their implications for future violence prevention
      efforts.

PMID- 16563645
TI  - A cybernetic view on wind-up.
AB  - Wind-up is described traditionally as a frequency dependent increase in the
      excitability of spinal cord neurons, evoked by electrical stimulation of afferent
      C-fibers. Different kinds of wind-up have been reported, but wind-up of Abeta
      fibers in hyperalgesic states has gained little attention. In this paper, we
      present a cybernetic view on Abeta fiber wind-up and consider the involved
      molecular mechanisms as feedback and feedforward processes. Furthermore, our
      previous hypothesis, the sprouting phenomenon, is included in this view.
      Considering the proposed model, wind-up in hyperalgesic states might leave out in
      three different ways: (1) blocking the NMDA receptors by increasing extracellular
      Mg2+, 2) blocking the receptors and channels that contribute to Ca2+ inward
      current, and 3) blocking the Abeta fibers by local anesthetics. It seems that
      wind-up may be inhibited more effectively by using these three blocking
      mechanisms simultaneously, because in this case, the feedback process (main
      controller), the feedforward process (trigger), and Abeta stimulation (trigger)
      would be inhibited concurrently. Wind up may aggravate the pain in clinical
      hyperalgesic situations such as post-surgical states, some neuropathic pains,
      fibromyalgia syndrome, and post-herpetic neuralgia. Surely, clinical studies are
      needed to validate the effectiveness of our abovementioned suggestions in
      relieving such clinical pains.

PMID- 16563646
TI  - SIRT1: cellular senescence, cancer and organismal aging?

PMID- 16563647
TI  - Dynamic behavior of gap junctions in each cardiac cycle: a novel view on the
      electrical coupling of normal cardiocytes.
AB  - Two main mechanisms have been suggested for the propagation of action potentials
      in cardiac muscle cells: (1) the free flow of local circuit current through gap
      junctions and (2) the effect of electrical field. Different evidences confirm
      each of two mechanisms. We think that gap junctions are not continuously open in
      a normal heart cycle; instead, they open and close intermittently. In other
      words, gap junction has a dynamic behavior in each cardiac cycle, managing
      different routes of propagation in the diverse moments of normal cycle. Gap
      junctions could be open in phases 0, 1, 3, 4 and close in phase 2 (plateau) of
      action potential. Whenever gap junction is open, conduction can be fulfilled
      rapidly by current flow and whenever it is closed, the electrical field will be
      the main route of propagation. When the prejunctional cell is in the peak of
      action potential(AP), gap junction is closed and the postjunctional cell should
      use the electrical field to be stimulated. Then, when the prejunctional cell
      comes to the end of AP, the gap junction opens and current will potentiate the
      rising phase of AP in the postjunctional cell. Moreover, this process causes
      accumulation of calcium in the postjunctional cell near phase 2. We believe that
      our hypothesis on the mechanism of cardiac action potential propagation may have
      exciting advantages. This novel view on gap junction dynamic behavior may be
      useful for better exploitation of drugs or designing new remedies in arrhythmias.
      We also hypothesize that in conditions as cardiac failure, in which cardiac
      contractility is diminished and increasing intracellular calcium concentration is
      needed, gap junction closing drugs may be effective. It is worth noting that
      future clinical studies are needed to validate these predictions.

PMID- 16563648
TI  - Promiscuous-binding of insulin to adipocyte receptors in diabetes mellitus type 2
      may be associated with overproduction of cyclic AMP (cAMP).

PMID- 16563649
TI  - Apoptosis mediated by cytolytic molecules might be responsible for maintenance of
      psoriatic plaques.
AB  - Psoriasis is a chronic hyperproliferative skin disease characterized by
      keratinocyte hyperproliferation and inflammation. It is generally considered as
      an autoimmune disease mediated by T cells. The precise mechanism of triggering
      keratinocyte hyperproliferation is as yet unknown. Apoptosis seems to be
      important in the maintenance of skin cell homeostasis as well as in the
      pathogenesis of some skin diseases. We hypothesize how apoptosis mediated by
      cytolytic mechanisms could be involved in initiating and maintenance of psoriatic
      plaque. Increased keratinocyte hyperproliferation might develop as a consequence
      of failure to remove self-reactive T cells by apoptosis that in other way cause
      significant keratinocyte damage. Apoptotic keratinocytes might trigger an injury
      response program causing regenerative hyperplasia of epidermal keratinocytes.
      Another possibility is that the failure to eliminate these abnormal keratinocytes
      could result in the persistence of chronic inflammatory conditions constantly
      recruiting specific T cells. Increased epidermal thickness in psoriasis could be
      also explained by imbalance between the expression of pro- and anti-apoptotic
      proteins. Epidermal keratinocytes have the ability to produce cytolytic
      molecules, thus they might also have the potential to protect the epidermis from
      T cell-mediated damage. In conclusion, hyperproliferation of psoriatic
      keratinocytes might be partly due to changes in the keratinocyte expression of
      pro- and anti-apoptotic genes, partly to the damaged keratinocytes triggering an
      inappropriate wound repair response and partly by the failure to eliminate these
      abnormal keratinocytes resulting in the persistence of chronic inflammation. Each
      of the proposed mechanisms might be a possible therapeutic target mainly by new
      immunomodulatory agents.

PMID- 16563650
TI  - Expression of extracellular matrix-degrading proteins in classic, atypical, and
      anaplastic meningiomas.
AB  - Although the majority of meningiomas, commonly benign tumors (WHO I), are
      amenable to surgical resection, a percentage of up to 3% will recur as higher
      grade meningiomas with potential brain invasion. Our study aims at the in situ
      identification of proteolytic, extracellular matrix-degrading enzymes in a broad
      spectrum of meningiomas. We examined 80 meningiomas (50 classic meningiomas WHO
      I, 19 meningiomas WHO II, including atypical, chordoid, and clear cell types, as
      well as 11 anaplastic meningiomas WHO III) for the immunohistochemical expression
      patterns of cathepsin D and metalloproteinases MMP-2 and MMP-9. Meningiomas of
      all types and grades revealed a distinct expression of MMP-9 and cathepsin D,
      while MMP-2 was found predominantly in WHO II and III meningiomas. There was a
      significant increase in positive tumor cells from WHO grade I to II and III for
      MMP-2 (p<0.001), but not for cathepsin D (p=0.099). MMP-9 displayed an increased
      number of positive tumor cells from WHO grade I to II, but a decrease in WHO III
      meningiomas (p<0.002). Routine screening for the expression of metalloproteinases
      and cathepsin D will not reveal any new diagnostically or prognostically relevant
      information. However, these factors may represent a potential target for
      pharmacological blocking as an anti-invasive therapy.

PMID- 16563651
TI  - HSP60 expression during carcinogenesis: where is the pilot?

PMID- 16563652
TI  - A simple and economical method for the manual construction of well-aligned tissue
      arrays.
AB  - Tissue array technology has allowed a substantial progression of studies
      correlating molecular and immunohistochemical findings with clinico-pathological
      information. Array construction presents technical difficulties and tissue
      arrayers are expensive, particularly for small and medium sized laboratories. We
      describe a simple manual method for producing well-aligned tissue arrays using a
      hand-made paper mold which can successfully perform immunohistochemical staining.
      All 200 tissue samples were collected and constructed into blocks by the paper
      mold. The tissue arrays were smoothly sectioned using a standard microtome and
      performed for a panel of immunohistochemical study with satisfactory results.
      This alterative method for building custom arrays could be applied in any
      laboratory and is both simple and economical.

PMID- 16563653
TI  - Phase I study of hypofractionated dose-escalated thoracic radiotherapy for
      limited-stage small-cell lung cancer.
AB  - PURPOSE: To determine the maximal tolerated dose of hypofractionated thoracic
      radiotherapy with concurrent chemotherapy for limited-stage small-cell lung
      cancer patients. METHODS AND MATERIALS: Three radiotherapy regimens were used.
      Radiotherapy was given in two phases: patients initially received 20 Gy in 10
      fractions to gross tumor plus uninvolved mediastinal nodes, followed by a boost
      to gross disease of 30, 38, or 42 Gy in 15 fractions. Radiotherapy was planned
      with conformal techniques. All patients received four cycles of cisplatin (25
      mg/m2) and etoposide (100 mg/m2) chemotherapy. Radiotherapy commenced with Day 1
      of Cycle 2 of chemotherapy. All complete/near-complete responders were offered
      prophylactic cranial irradiation. The maximal tolerated dose of radiotherapy was
      based on the dose that caused unacceptably high rates of radiotherapy-related
      toxicity. RESULTS: Thirteen patients were accrued. All patients who commenced
      radiotherapy received all prescribed chemo- and radiotherapy. There were no
      treatment-related deaths. There was one Grade 3 acute nonhematologic toxicity in
      the 50-Gy group. Of the 6 patients given 58 Gy, 3 experienced acute Grade 3
      esophagitis. With a median follow-up of 7 months, median overall survival was 9.5
      months. CONCLUSIONS: The maximal tolerated dose of thoracic radiotherapy with
      concurrent chemotherapy on this trial was 50 Gy in 25 daily fractions.

PMID- 16563654
TI  - Rectal-wall dose dependence on postplan timing after permanent-seed prostate
      brachytherapy.
AB  - PURPOSE: Dose to rectal wall after permanent-seed prostate brachytherapy is
      dependent on distance between posterior prostatic seeds and anterior rectal wall
      and is influenced by postimplant periprostatic edema. We analyzed the effect of
      postplan timing on anterior rectal-wall dose. METHODS AND MATERIALS: Twenty
      patients received permanent seed 125I brachytherapy as monotherapy (145 Gy).
      Implants were preplanned by use of transrectal ultrasound (TRUS) and carried out
      by use of preloaded needles. Postimplant dosimetry was calculated by use of
      magnetic resonance imaging-computed tomography fusion on Days 1, 8, and 30. The
      anterior rectal-wall dose is reported as the isodose enclosing 1.0 or 2.0 cc of
      rectal wall and as the RV100 in cc. RESULTS: The dose to rectal wall increased
      progressively over time. The median increase in dose to 1.0 cc of rectal wall (RD
      [1 cc]) from Day 1 to 30 was 39.2 Gy (p < 0.001). RV100 increased from a median
      of 0.07 cc on Day 1 to 0.67 cc on Day 30. The most significant predictor of
      rectal-wall dose (RD [1 cc], RD [2 cc], or RV100) was the time of evaluation (p <
      0.001). CONCLUSION: Although periprostatic edema cannot be quantified by
      postimplant imaging, the dose to the anterior rectal wall increases significantly
      over time as prostatic and periprostatic edema resolve. Critical-organ dose
      reporting and guidelines for minimizing toxicity must take into account the time
      of the assessment.

PMID- 16563655
TI  - Optimization of combination therapy of arsenic trioxide and fractionated
      radiotherapy for malignant glioma.
AB  - PURPOSE: The primary objective was to optimize the combined treatment regimen
      using arsenic trioxide (ATO) and fractionated radiotherapy for the treatment of
      malignant glioma. METHODS AND MATERIALS: Nude mice with human glioma xenograft
      tumors were treated with fractionated local tumor radiation of 250
      cGy/fraction/day and 5 mg/kg ATO for 5-10 days. RESULTS: Time course experiments
      demonstrated that maximal tumor growth delay occurred when ATO was administered
      between 0 and 4 h after radiation. The combination treatment of ATO and radiation
      synergistically inhibited tumor growth and produced a tumor growth delay time of
      13.2 days, compared with 1.4 days and 6.5 days for ATO and radiation alone (p <
      0.01), respectively. The use of concurrent therapy of radiation and ATO
      initially, followed by ATO as maintenance therapy, was superior to the use of
      preloading with ATO before combined therapy and produced a tumor growth delay
      time of 22.7 days as compared with 11.7 days for the ATO preloading regimen (p <
      0.01). The maintenance dose of ATO after concurrent therapy was effective and
      important for continued inhibition of tumor growth. CONCLUSIONS: The combined use
      of fractionated radiation and ATO is effective for the treatment of glioma
      xenograft tumors. ATO was most effective when administered 0-4 h after radiation
      without pretreatment with ATO. These results have important implications for the
      optimization of treatment regimen using ATO and fractionated radiotherapy for the
      treatment of brain tumors.

PMID- 16563656
TI  - Repeated proton beam therapy for hepatocellular carcinoma.
AB  - PURPOSE: To retrospectively evaluate the safety and effectiveness of repeated
      proton beam therapy for newly developed or recurrent hepatocellular carcinoma
      (HCC). METHODS AND MATERIALS: From June 1989 through July 2000, 225 patients with
      HCC underwent their first course of proton beam therapy at the University of
      Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were
      retrospectively reviewed in this study. Median interval between the first and
      second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy
      in 16 fractions and 66 Gy in 16 fractions were given for the first course and the
      rest of the courses, respectively. RESULTS: The 5-year survival rate and median
      survival period from the beginning of the first course for the 27 patients were
      55.6% and 62.2 months, respectively. Five-year local control rate for the 68
      lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with
      class C before the last course suffered from acute hepatic failure. CONCLUSIONS:
      Repeated proton beam therapy for HCC is safe when the patient has a target in the
      peripheral region of the liver and liver function is Child-Pugh class A.

PMID- 16563657
TI  - Effect of combined treatment with salvage radiotherapy plus androgen suppression
      on quality of life in patients with recurrent prostate cancer after radical
      prostatectomy.
AB  - PURPOSE: To examine the effect of salvage radiotherapy (RT) plus 2-year androgen
      suppression (AS) on quality of life (QOL). METHODS AND MATERIALS: A total of 74
      patients with biopsy-proven local recurrence or PSA relapse after radical
      prostatectomy were treated with salvage RT plus 2-year AS, as per a phase II
      study. Quality of life was prospectively assessed with the European Organization
      for Research and Treatment of Cancer Quality of Life Questionnaire 30-Item
      Version 3.0 with the added prostate cancer-specific module at baseline and
      predefined follow-up visits. RESULTS: Patients experienced a significant increase
      in bowel dysfunction (23%) by the end of RT (p < 0.0001). This bowel dysfunction
      improved after RT but remained slightly elevated (5-10%) throughout the 2-year AS
      period. This extent of residual bowel dysfunction would be considered of minimal
      clinical importance. A similar, but less pronounced, pattern of change did occur
      for urinary dysfunction. Erectile function showed no change during RT, but had an
      abrupt decline (10%) with initiation of AS that was of moderate clinical
      significance (p < 0.01). None of the other QOL domains demonstrated a persistent,
      significant change from baseline that would be considered of major clinical
      significance. CONCLUSION: The combined treatment with salvage RT plus 2-year AS
      had relatively minor long-term effects on QOL.

PMID- 16563658
TI  - Comparison of ultrasound and implanted seed marker prostate localization methods:
      Implications for image-guided radiotherapy.
AB  - PURPOSE: To analyze two methods of image-guided radiotherapy (IGRT) for external
      beam radiotherapy of prostate cancer. METHODS AND MATERIALS: The prostate was
      localized by ultrasound (US) in lateral (left/right), vertical (anteroposterior),
      and longitudinal (superior/inferior) dimensions and then by fiducial seed marker
      (SM) kV X-ray. Assuming initial setup to skin marks as the origin, the mean
      suggested shifts (for all dimensions) were hypothesized to be similar and within
      1 mm of the origin. The three-dimensional distance discrepancy between suggested
      SM and US shift points was calculated. We hypothesized a mean discrepancy >5 mm
      as clinically significant. RESULTS: From 40 patients, 1019 US/SM measurements
      were obtained. Lateral, vertical, and longitudinal dimensional comparisons reveal
      statistically significant differences in mean shifts (p < 0.0001 for all). US
      dimensional shifts reveal significantly greater variability. The US three
      dimensional vector is greater and more variable than the SM vector (p < 0.0001).
      The mean US/SM three-dimensional distance discrepancy is 8.8 mm (significantly >5
      mm, p < 0.0001). CONCLUSIONS: Ultrasound and SM methods suggest different shifts.
      US data reveal greater systematic/random error vs. SM data. The US data suggest
      larger PTV expansion margins (approximately 9 mm) are necessary for US IGRT vs.
      SM IGRT (approximately 3 mm). The hypotheses that US and SM methods suggest
      similar shifts and that the mean US/SM three-dimensional distance discrepancy is
      < or =5 mm are rejected.

PMID- 16563659
TI  - An immunohistochemical assessment of hypoxia in prostate carcinoma using
      pimonidazole: implications for radioresistance.
AB  - PURPOSE: To investigate the presence of hypoxia in human prostate carcinoma by
      using pimonidazole immunohistochemical labeling in radical prostatectomy
      specimens. METHODS AND MATERIALS: Forty-three patients (median age, 69 years;
      range, 49-83 years) with localized prostate adenocarcinoma received 0.5 gm/m2
      i.v. pimonidazole 16-24 h before radical prostatectomy. Hypoxia was detected with
      a monoclonal antibody directed against pimonidazole and scored in formalin-fixed,
      paraffin-embedded sections. Median and maximal vessel counts were measured with
      CD34. RESULTS: Thirty-seven patients completed the study. Pimonidazole binding
      was present in prostate carcinomas in 34 of 37 patients (92%) and in benign
      prostatic hyperplasia in 35 of 37 patients (95%). A positive correlation of 3+
      pimonidazole binding with Gleason score was demonstrated (Spearman's rank, p =
      0.044). Vascularity scores did not correlate with hypoxic status or clinical
      prognostic parameters. CONCLUSION: Prostate carcinoma and benign prostatic
      hyperplasia have significant areas of hypoxia; greater hypoxia scores are seen
      with more aggressive prostate cancer. It is postulated that a hypoxic
      microenvironment within the prostate might be responsible for the promotion of
      secondary genetic alterations and angiogenic stimulation, leading to malignant
      progression, a more aggressive cell phenotype, and greater radioresistance.
      Modification of radiation regimens to specifically target hypoxia might improve
      local tumor control.

PMID- 16563660
TI  - Antineoplastic activity of selected constituents of Duguetia glabriuscula.
AB  - The cytotoxic effects of seven constituents isolated from Duguetia glabriuscula
      were evaluated against Hep2 human larynx carcinoma cells. The cytotoxicity
      exhibited by beta-sitosterol was as strong as that of cis-platin. (+)
      Alloaromadendran-10,14beta-diol caused inhibition of cellular growth with IC50
      values lower than 25 microg/ml, a feature that was considered as revealing
      significant activity. Polycarpol showed borderline cytotoxicity, whereas the
      other compounds were inactive.

PMID- 16563661
TI  - The DNA repair complex DNA-PK, a pharmacological target in cancer chemotherapy
      and radiotherapy.
AB  - A line of investigation in the search for sensitizing tumor cells to chemotherapy
      or radiotherapy relies on the selection of DNA repair inhibitors. In the area of
      DNA repair mechanisms, DNA-dependent protein kinase (DNA-PK) represents a key
      complex. Indeed DNA-PK is involved in the non-homologous end joining (NHEJ)
      process that corresponds to the major activity responsible for cell survival
      after ionizing radiation or chemotherapeutic treatment producing DNA double
      strand breaks. DNA-PK belongs to the PI3-K related kinase family and specific
      inhibitors have been recently selected and evaluated as radio- and chemo
      sensitizers. These drugs, along with other ways to inhibit the DSBs repair
      process, are presented and discussed.

PMID- 16563662
TI  - Impact of Drug Formulation on Abuse Liability, Safety and Regulatory Decisions.
      Proceedings and abstracts of a conference, Bethesda, Maryland, USA, April 2005.
AB  - In light of recent increased publicity concerning diversion and tampering with
      prescription medications, new formulations are being widely considered as a
      strategy to reduce risk. These approaches are occurring in a context where
      regulatory, law enforcement and research frameworks have not been fully developed
      to accommodate these new formulations. As a result, College on Problems of Drug
      Dependence sponsored the conference "Impact of Drug Formulation on Abuse
      Liability, Safety and Regulatory Decisions," held in North Bethesda, Maryland in
      April, 2005 with Edward Sellers and Charles R. Schuster serving as co-chairs. To
      accomplish the desired goals, papers on key topics were commissioned and these
      papers were presented at the conference along with submitted presentations from
      other invitees. This supplement to Drug and Alcohol Dependence contains the
      manuscripts arising from presentations at the meeting, a summary of
      recommendations, and abstracts of the other submitted papers. Our hope is that
      the proceedings of this meeting will contribute importantly to the consideration
      of the research, regulatory and public health issues raised by the development of
      new formulations designed to reduce the diversion and abuse of medications.

PMID- 16563663
TI  - Abuse of prescription drugs and the risk of addiction.
AB  - Abuse of several categories of prescription drugs has increased markedly in the
      United States in the past decade and is now at alarming levels for certain
      agents, especially opioid analgesics and stimulants. Prescription drugs of abuse
      fit into the same pharmacological classes as their non-prescription counterparts.
      Thus, the potential factors associated with abuse or addiction versus safe
      therapeutic use of these agents relates to the expected variables: dose, route of
      administration, co-administration with other drugs, context of use, and
      expectations. Future scientific work on prescription drug abuse will include
      identification of clinical practices that minimize the risks of addiction, the
      development of guidelines for early detection and management of addiction, and
      the development of clinically effective agents that minimize the risks for abuse.
      With the high rates of prescription drug abuse among teenagers in the United
      States, a particularly urgent priority is the investigation of best practices for
      effective prevention and treatment for adolescents, as well as the development of
      strategies to reduce diversion and abuse of medications intended for medical use.

PMID- 16563664
TI  - Molecular characterization of pestiviruses isolated from bovines in Chile.
AB  - Thirty-three pestiviruses isolated from bovines on different farms in Chile were
      characterized at the molecular level. The 5'-untranslated region (5'UTR) of the
      isolates was amplified by reverse transcription-polymerase chain reaction (RT
      PCR) and subsequently digested with restriction enzymes (RE) Bgl I, Xho I and Pst
      I. Furthermore, the isolates were amplified by differential RT-PCR, which
      selectively amplified bovine viral diarrhea virus type 2 (BVDV-2) but not bovine
      viral diarrhea virus type 1 (BVDV-1). Of the 33 isolates, 16 were classified as
      BVDV-1 and 17 as BVDV-2. Phylogenetic analysis of the PCR-amplified fragments
      from 14 isolates showed the presence of viruses belonging to the BVDV-1a, BVDV
      1b, BVDV-1c, and BVDV-2 types. Antigenicity of some viruses belonging to both
      genotypes was studied by cross-seroneutralization, revealing great antigenic
      differences among them. It is concluded that BVDV viruses circulating in Chile
      are genetically and antigenically heterogeneous, comprising isolates of
      genogroups 1 and 2.

PMID- 16563665
TI  - A nucleotide mutation associated with fluoroquinolone resistance observed in gyrA
      of in vitro obtained Rhodococcus equi mutants.
AB  - In this study, the quinolone resistance-determining region (QRDR) in gyrA and
      gyrB of in vitro fluoroquinolone-resistant Rhodococcus equi mutants was
      sequenced. These mutants were selected from four R. equi strains on blood agar
      plates containing ciprofloxacin or enrofloxacin. Each mutant became 8- to 64 or
      greater-fold resistant to fluoroquinolones compared with their parent strains.
      From the results of sequence analysis of QRDR in gyrA and gyrB, a nucleotide
      mutation of codon GAC for GGC in gyrA was detected in all mutants, but no
      mutation was observed in gyrB. This mutation leads to amino acid substitution of
      Asp for Gly in putative GyrA in R. equi. The position of this substitution
      corresponds to position 87 of GyrA in Escherichia coli. Our results suggest that
      the mutation of QRDR in gyrA, which was observed in in vitro fluoroquinolone
      resistant R. equi mutants in this study, is closely associated with
      fluoroquinolone resistance.

PMID- 16563666
TI  - The perinatal management of gastroschisis.
AB  - Gastroschisis is increasing in frequency and is becoming a common condition. It
      is now invariably detected antenatally and although the long-term outcome in the
      majority of cases is excellent, the existence of both fetal and postnatal
      complications has led to variations in practice to try to optimise outcome. This
      article reviews the evidence for some of these variations where such evidence
      exists and provides a contemporary view of best practice where it does not.

PMID- 16563667
TI  - Influence of cadmium on murine thymocytes: potentiation of apoptosis and
      oxidative stress.
AB  - Cadmium (Cd) is a well-known environmental carcinogen and a potent
      immunotoxicant. It induces thymocyte apoptosis in vitro. However, the mode of
      action is unclear. In this study, we examined the effect of Cd (10, 25 and
      50microM) on mitochondrial membrane potential and caspase-3 as well as oxidative
      stress markers in murine thymocytes. The cadmium induced apoptosis occurred in a
      concentration and time dependent manner. The early markers of apoptosis-loss in
      mitochondrial membrane potential and caspase-3 activation were evident as early
      as 1.5h by 50microM Cd. Enhanced reactive oxygen species (ROS) generation and
      glutathione (GSH) depletion were observed at 60min, prior to the lowering of
      mitochondrial membrane potential. The Cd induced DNA damage as depicted by
      internucleosomal fragmentation on agarose and histone associated mono- and
      oligonucleosomes detection by ELISA, corrobated with the apoptotic DNA (sub-G(1)
      population) and total apoptotic cells by Annexin V binding assay. The number of
      cells in sub-G(1) population increased to 66% at 50microM Cd concentration and
      the distribution of early and late apoptotic cells was 47% and 15%, respectively.
      Addition of N-acetylcysteine and pyrrolidine dithiocarbamate (thiol antioxidants)
      to the Cd treated cells, lowered the sub-G(1) population, inhibited the ROS
      generation and raised the GSH levels. Buthionine sulfoximine (GSH depletor) on
      the other hand, enhanced both the ROS production and the sub-G(1) fraction. These
      results clearly demonstrate the apoptogenic potential of Cd in murine thymocytes,
      following mitochondrial membrane depolarization, caspase activation and ROS and
      GSH acting as critical mediators.

PMID- 16563668
TI  - In silico search of putative adverse drug reaction related proteins as a
      potential tool for facilitating drug adverse effect prediction.
AB  - Adverse drug reaction (ADR) is a significant issue in drug development and post
      market applications. Different experimental and computational approaches need to
      be explored for predicting ADRs due to the complexity of their molecular
      mechanisms. One approach for predicting ADRs of a drug is to search for its
      interaction with ADR-related proteins (ADRRPs). In this work, this approach is
      tested on 11 marketed anti-HIV drugs covering protease inhibitors (PIs),
      nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse
      transcriptase inhibitors (NNRTIs). An in silico drug target search method,
      INVDOCK, is used for searching the ADRRPs of each of these drugs. The
      corresponding ADRs of the predicted ADRRPs of each of these drugs are compared to
      clinically observed ADRs reported in the literature. It is found that 86-89% of
      the INVDOCK predicted ADRs of these drugs are consistent with the literature
      reported ADRs, and about 67-100% of the literature-reported ADRs of these drugs
      to various degrees is agreed with INVDOCK predictions. These results suggest that
      it is feasible to explore in silico ADRRP search methods for facilitating drug
      toxicity prediction.

PMID- 16563669
TI  - The safety of tibolone in epithelial ovarian cancer patients.
AB  - OBJECTIVES: We evaluated whether tibolone had an adverse effect on the
      progression free survival and overall survival of epithelial ovarian cancer
      patients. METHODS: Forty-two tibolone users and 33 non-users who had been
      surgically managed for epithelial ovarian cancer at Gil Medical Center, Inchon,
      Korea, from January 1997 to December 2003 were reviewed retrospectively. RESULTS:
      There were no statistically significant differences in age, stage, histology,
      grade and surgical optimality between tibolone users and non-users. The
      progression free survival at 36 months was 60.0% among the users compared with
      61.5% among the non-users (p=0.92). There was also no significant difference in
      the overall survival between two groups (p=0.30). For stage IIIc patients
      according to tibolone using, there were no significant differences in the
      progression free survival (p=0.86) and overall survival (p=0.36) between tibolone
      users and non-users. CONCLUSIONS: There was no evidence that tibolone had
      detrimental effects on the progression free survival and overall survival of
      epithelial ovarian cancer patients. So, tibolone could be used in these patients.

PMID- 16563670
TI  - Seasonal onset of menopause.

PMID- 16563671
TI  - Preparation and characteristics of monostearin nanostructured lipid carriers.
AB  - Nanostuctured lipid carriers (NLC) consisted of solid lipid and liquid lipid are
      a new type of lipid nanoparticles, which offer the advantage of improved drug
      loading capacity and release properties. In this study, solvent diffusion method
      was employed to produce NLC. Monostearin (MS) and caprylic/capric triglycerides
      (CT) were chosen as the solid lipid and liquid lipid. Clobetasol propionate used
      as a model drug was incorporated into the NLC. The influences of preparation
      temperature and CT content on physicochemical properties of the NLC were
      characterized. As a result, monostearin solid lipid nanoparticles (without CT
      content, SLN) obtained at higher temperature (70 degrees C) exhibited slightly
      higher drug loading capacity than that of 0 degrees C (P < 0.05). In contrast,
      the production temperature made little effect on NLC drug loading capacity (P >
      0.05). The improved drug loading capacity was observed for NLC and it enhanced
      with increasing the CT content in NLC. The results were explained by differential
      scanning calorimetry (DSC) measurement for NLC. The incorporation of CT to NLC
      led to crystal order disturbance and thus left more space to accommodate drug
      molecules. NLC displayed a good ability to reduce the drug expulsion in storage
      compared to SLN. The in vitro release behaviors of NLC were dependent on the
      production temperature and CT content. NLC obtained at 70 degrees C exhibited
      biphasic drug release pattern with burst release at the initial 8h and prolonged
      release afterwards, whereas NLC obtained at 0 degrees C showed basically
      sustained drug release throughout the release time. The drug release rates were
      increased with increasing the CT content. These results indicated that the NLC
      produced by solvent diffusion method could potentially be exploited as a carrier
      with improved drug loading capacity and controlled drug release.

PMID- 16563672
TI  - In vitro characterization and transfection of IL-2 gene complexes.
AB  - BACKGROUND: Interleukin-2 used in the treatment of malignant tumors has an anti
      tumor efficacy. In this study, we have studied in vitro characterization and
      transfection efficiency of a plasmid encoding hIL-2, pCXWN-hIL-2, complexed to
      chitosan, polyethylenimine or DOTAP with varying ratios. METHODS: Plasmid DNA was
      amplified in Escherichia coli DH5alpha and isolated by alkali lysis method. The
      pDNA/chitosan, pDNA/PEI or pDNA/DOTAP complexes were analyzed by agarose gel
      electrophoresis for complex formation and by ESEM image analysis system for the
      morphology and DNA/medium relationship of complexes. DNase stability, the
      particle size and zeta potential values of complexes were determined.
      Transfection efficiencies of resulting complexes in two different cell lines were
      assayed by ELISA method. RESULTS: Conclusively, a transfection activity was
      observed in both cell lines (HeLa and Swiss3T3) with the order of
      pDNA/DOTAP>pDNA/PEI>pDNA/chitosan complexes. We have observed that the
      transfection efficiency was higher in HeLa cell line compared to Swiss3T3 cell
      line. CONCLUSION: The physicochemical studies like stability, particle size and
      zeta potential, showed a relationship between the properties of a complex and its
      transfection efficiency.

PMID- 16563673
TI  - Controlled release of a self-emulsifying formulation from a tablet dosage form:
      stability assessment and optimization of some processing parameters.
AB  - The objective of this study was to evaluate the effect of some processing
      parameters on the release of lipid formulation from a tablet dosage form. A 17
      run, face-centered cubic design was employed to evaluate the effect of colloidal
      silicates (X(1)), magnesium stearate mixing time (X(2)), and compression force
      (X(3)) on flow, hardness, and dissolution of Coenzyme Q(10) (CoQ(10)) lipid
      formulation from a tablet dosage form. The optimized formulation was subsequently
      subjected to a short-term accelerated stability study. All preparations had a
      flowability index values ranging from 77 to 90. The cumulative percent of CoQ(10)
      released within 8h (Y(5)) ranged from 40.6% to 90% and was expressed by the
      following polynomial equation: Y(5)=49.78-16.36X(1)+2.90X(2)-3.11X(3)
      0.37X(1)X(2)+1.06X(1)X(3)-1.02X(2)X(3)+11.98X(1)(2)+10.63X(2)(2)-7.10X(3)(2).
      When stored at 4 degrees C, dissolution rates were retained for up to 3 months.
      Storage at higher temperatures, however, accelerated lipid release and caused
      leakage, and loss of hardness. Processing parameters have a profound effect on
      the release of lipid formulations from their solid carriers. While optimized
      controlled release formulations could be attained, further considerations should
      be made to prepare "liquisolids" that are physically stable at higher storage
      temperatures.

PMID- 16563674
TI  - Prospects of formulating proteins/peptides as aerosols for pulmonary drug
      delivery.
AB  - Formulation of proteins/peptides for therapeutic uses has often posed some
      challenges to drug formulators. The main problem is the relatively weak forces
      involved in the native conformation of these proteins and so making them quite
      labile. Furthermore, their susceptibility to proteolytic enzymes in the gut makes
      oral administration quite challenging. While various routes like, ocular,
      transdermal, nasal and buccal have been tried, none of these routes has proved to
      be a potential alternative to the invasive injection. However, various studies
      have been performed on the formulation of these proteins as aerosols for
      pulmonary delivery and promising results have been obtained. This article looks
      at the prospects of inhaled proteins as a delivery route for systemic activity.

PMID- 16563675
TI  - Extractables/leachables from plastic tubing used in product manufacturing.
AB  - While the ability of packaging systems to contribute leached substances to
      finished drug products is well established, increasing interest is being focused
      on the potential contamination of drug substances by plastic materials
      encountered during their production. The direct contact of such plastic parts
      (such as tubing, gaskets, filters and temporary storage containers) with the drug
      substance at some point in its production raises the possibility that plastic
      related contaminants (leachables) may be present in the finished drug product. In
      this study, eight tubing materials potentially encountered in pharmaceutical
      production facilities, including six silicone materials and two Santoprene
      materials, were characterized for their extractable substances by static
      extraction coupled with comprehensive chemical characterization of the resulting
      extracts. Based on the extractables profiles thus generated, target leachables
      were identified for each tubing material. The accumulation of these target
      leachables was studied by subjecting the tubing to dynamic flow, simulated use
      extractions. The primary organic extractables from the silicone tubing were a
      homologous series of silicone oligomers, with most of the tubings demonstrating a
      unique distribution of oligomers. Several of the silicone tubings also possessed
      extractable dioctyl phthalate and dioctyl adipate. The primary organic
      extractables from the Santoprene-type tubing included a number of phthalates, a
      series of alkyl phenols and decomposition products of Irganox-type antioxidants.
      Inorganic extractables associated with many of the tubings included Ca, Mg, Zn
      and B. In general, the levels of targeted leachables extracted from the tubing
      materials under simulated use (flow) conditions was much smaller than the total
      amount of these leachables in the tubing.

PMID- 16563676
TI  - Evaluation of Inutec SP1 as a new carrier in the formulation of solid dispersions
      for poorly soluble drugs.
AB  - Solid dispersions made up of itraconazole and Inutec SP1, a new polymeric
      surfactant, were prepared by spray drying and hot-stage extrusion. Differential
      scanning calorimetry (DSC) and X-ray powder diffraction (XRD) were used to
      evaluate the miscibility of the components of the dispersions, and dissolution
      experiments were performed in simulated gastric fluid without pepsin (SGFsp) to
      evaluate the pharmaceutical performance of itraconazole from the solid
      dispersions. DSC analysis showed that the solid dispersions are phase separated
      systems made up of glassy and crystalline itraconazole and amorphous Inutec SP1.
      The amount of crystalline drug substance was higher in the dispersions prepared
      by hot-stage extrusion and was clearly a function of the drug concentration.
      Since no crystallinity could be detected by XRD points to the fact that the
      crystallites formed are very small in size. Despite the presence of glassy and
      crystalline clusters, the dissolution properties of the solid dispersions were
      significantly improved in comparison to pure itraconazole (glassy or crystalline)
      or physical mixtures with Inutec SP1. This study proves the potential of the new
      polymeric surfactant as a carrier in the formulation of solid dispersions for
      poorly soluble drugs.

PMID- 16563677
TI  - The apoptosis effect of hispolon from Phellinus linteus (Berkeley & Curtis) Teng
      on human epidermoid KB cells.
AB  - Phellinus linteus (Berkeley & Curtis) Teng, a well-known fungus of the genus
      Phellinus in the family of Hymenochaetaceae, is being increasingly used to treat
      a wide variety of disease processes such as oral ulcer, gastroenteric disorder,
      inflammation, lymphatic disease, and various cancers. However, the mechanism
      underlying its anti-oral cancer effect is poorly understood. In the present
      study, we prepared the ethanol extract of Phellinus linteus as a crude drug, and
      then obtained the active component hispolon by bioassay-guided isolation.
      Hispolon showed a dose-dependent inhibition of human epidermoid KB cell
      proliferation with IC50 of 4.62+/-0.16 microg/ml. Furthermore, it was revealed
      that hispolon could induce human epidermoid KB cell apoptosis with the
      characteristic of a DNA ladder, and with a significant increase of sub-G1. This
      process was accompanied by the collapse of mitochondrial membrane potential, the
      release of cytochrome c and the activation of Caspase-3. These results
      demonstrated that hispolon induced the death of KB cells through a mitochondria
      mediated apoptotic pathway. We propose that Phellinus linteus and its effective
      components could be used as an anti-oral cancer drug for future studies.

PMID- 16563678
TI  - Dental age estimation through volume matching of teeth imaged by cone-beam CT.
AB  - A custom-made voxel counting software for calculating the ratio between pulp
      canal versus tooth volume based on cone-beam CT tooth images was developed and
      evaluated. The aim of this study was to attempt establishing a correlation
      between the chronological age of a certain individual and the pulp/tooth volume
      ratio of one of the teeth. Twenty-eight single rooted teeth of 19 individuals
      with well-known chronological age were scanned by the cone-beam CT (3D Accuitomo,
      J. Morita, Kyoto, Japan). Next the images were analyzed using the custom-made
      software. Linear regression analysis was performed. The results of the analysis
      showed a moderate correlation between the pulp/tooth volume ratio and biological
      age with a coefficient of determination (R2) of 0.29. Although the present work
      was limited to a pilot study, the developed technique showed promising results
      for dental age estimation in a non-invasive manner using cone-beam CT images in
      living individuals.

PMID- 16563679
TI  - New software for computer-assisted dental-data matching in Disaster Victim
      Identification and long-term missing persons investigations: "DAVID Web".
AB  - In 1997 an internally supported but unfunded pilot project at the Victorian
      Institute of Forensic Medicine (VIFM) Australia led to the development of a
      computer system which closely mimicked Interpol paperwork for the storage, later
      retrieval and tentative matching of the many AM and PM dental records that are
      often needed for rapid Disaster Victim Identification. The program was called
      "DAVID" (Disaster And Victim IDentification). It combined the skills of the VIFM
      Information Technology systems manager (VW), an experienced odontologist (JGC)
      and an expert database designer (JC); all current authors on this paper. Students
      did much of the writing of software to prescription from Monash University. The
      student group involved won an Australian Information Industry Award in
      recognition of the contribution the new software could have made to the DVI
      process. Unfortunately, the potential of the software was never realized because
      paradoxically the federal nature of Australia frequently thwarts uniformity of
      systems across the entire country. As a consequence, the final development of
      DAVID never took place. Given the recent problems encountered post-tsunami by the
      odontologists who were obliged to use the Plass Data system (Plass Data Software,
      Holbaek, Denmark) and with the impending risks imposed upon Victoria by the
      decision to host the Commonwealth Games in Melbourne during March 2006, funding
      was sought and obtained from the state government to update counter disaster
      preparedness at the VIFM. Some of these funds have been made available to upgrade
      and complete the DAVID project. In the wake of discussions between leading expert
      odontologists from around the world held in Geneva during July 2003 at the
      invitation of the International Committee of the Red Cross significant
      alterations to the initial design parameters of DAVID were proposed. This was
      part of broader discussions directed towards developing instruments which could
      be used by the ICRC's "The Missing" project that seeks to identify the victims of
      civil unrest and other atrocities. The most significant of these recommendations
      was that the next version of DAVID should be web-based allowing it to be used
      anywhere in the world and on any computer platform. The original intention that
      the software should be made available as freeware was strongly reiterated and
      endorsed. During 2005 these recommendations have been realized. This paper will
      describe the design parameters of the new software "DAVID web" and compare its
      features and performance with alternative packages.

PMID- 16563680
TI  - Large-scale in-vivo Caucasian facial soft tissue thickness database for
      craniofacial reconstruction.
AB  - A large-scale study of facial soft tissue depths of Caucasian adults was
      conducted. Over a 2-years period, 967 Caucasian subjects of both sexes, varying
      age and varying body mass index (BMI) were studied. A user-friendly and mobile
      ultrasound-based system was used to measure, in about 20min per subject, the soft
      tissue thickness at 52 facial landmarks including most of the landmarks used in
      previous studies. This system was previously validated on repeatability and
      accuracy [S. De Greef, P. Claes, W. Mollemans, M. Loubele, D. Vandermeulen, P.
      Suetens, G. Willems, Semi-automated ultrasound facial soft tissue depth
      registration: method and validation. J. Forensic Sci. 50 (2005)]. The data of 510
      women and 457 men were analyzed in order to update facial soft tissue depth
      charts of the contemporary Caucasian adult. Tables with the average thickness
      values for each landmark as well as the standard deviation and range, tabulated
      according to gender, age and BMI are reported. In addition, for each landmark and
      for both sexes separately, a multiple linear regression of thickness versus age
      and BMI is calculated. The lateral asymmetry of the face was analysed on an
      initial subset of 588 subjects showing negligible differences and thus warranting
      the unilateral measurements of the remaining subjects. The new dataset was
      statistically compared to three datasets for the Caucasian adults: the
      traditional datasets of Rhine and Moore [J.S. Rhine, C.E. Moore, Tables of facial
      tissue thickness of American Caucasoids in forensic anthropology. Maxwell Museum
      Technical series 1 (1984)] and Helmer [R. Helmer, Schadelidentifizierung durch
      elektronische bildmischung, Kriminalistik Verlag GmbH, Heidelberg, 1984] together
      with the most recent in vivo study by Manhein et al. [M.H. Manhein, G.A. Listi,
      R.E. Barsley, R. Musselman, N.E. Barrow, D.H. Ubelbaker, In vivo facial tissue
      depth measurements for children and adults. J. Forensic Sci. 45 (2000) 48-60].
      The large-scale database presented in this paper offers a denser sampling of the
      facial soft tissue depths of a more representative subset of the actual Caucasian
      population over the different age and body posture subcategories. This database
      can be used as an updated chart for manual and computer-based craniofacial
      approximation and allows more refined analyses of the possible factors affecting
      facial soft tissue depth.

PMID- 16563681
TI  - Implantation of an RFID-tag into human molars to reduce hard forensic
      identification labor. Part I: working principle.
AB  - Recently the tsunami disaster, the London bombings and the landfall of hurricane
      Katrina demonstrated once more the need for an accurate, quick and easy to handle
      identification system. The implantation of a radio frequency identification
      (RFID) tag into a human tooth and the read-out of its information may give an
      answer to this problem. A description is given of the modification of an existing
      RFID-tag that was made for veterinary use. This modified system was implanted in
      human molars using directly bonded resin composites. A protocol for tooth
      preparation and tag implantation was developed. A study of tag read-out patterns,
      revealed their accurate read-out distance range, the optimal site of RFID-tag
      implantation, assemblage of its components, and dimensions of the primary coil.
      It was found that disassembling the commercial RFID-tags was practically feasible
      and resulted in a properly working set-up. Further research is needed to optimize
      the design and the stability of RFID-tags for human identification purposes.

PMID- 16563682
TI  - A 'cold synthesis' of heroin and implications in heroin signature analysis
      utility of trifluoroacetic/acetic anhydride in the acetylation of morphine.
AB  - Treatment of morphine, at room temperature, with a mixture of trifluoroacetic
      anhydride (TFAA) and acetic acid (20-30min) affords good yields of heroin. GC-MS
      and HPLC examination shows that heroin produced by this route to be extremely
      clean, but the product contains slightly less heroin than observed via the more
      traditional acetic anhydride (AA) route (76.1% versus 83.55%); and greater
      quantities of 3-MAM and 6-MAM (6.9% versus 0.75% and 7.13% versus 0.63%). The
      concentration ratios of the major alkaloid impurities were found to be both
      production method (TFAA and AA) as well as morphine extraction methodology
      dependant. Data contained herein describe the impact of this new production
      method on current intelligence efforts, largely by-passing existing heroin
      signature programs and the UNDCP's efforts to restrict access to key synthetic
      precursors. Given the methodology dependency we find that examination of the
      major alkaloid ratios is unsuitable for the development of a new heroin signature
      program. Further examination of the TFAA methodology allowed the identification
      of TFAA specific marker compounds, namely bis-trifluoroacetylmorphine (30), 3
      trifluoroacetyl-6-acetylmorphine (31), 3-acetyl-6-trifluoroacetylmorphine (32)
      and trifluoroacetylcodeine (33). However, the hydrolytic lability of
      trifluroacetyl esters requires careful treatment of suspect samples, thus we
      propose a modification to existing HSP's in instances were the 6-MAM/WM ratio
      falls within the average minimum and maximum values of 6.17 and 17.32.

PMID- 16563683
TI  - Construction and use of facial archetypes in anthropology and syndrome diagnosis.
AB  - This paper describes the benefits of moving from recording simple Euclidian
      distances and angles between landmarks on the face to full three-dimensional
      visualisation and mapping using modern optical scanning techniques. Pilot
      experiments are reported on that strive to create facial archetypes which are
      accurately descriptive of various cohorts of people. Issues considered include
      variation amongst people of the same sex, age and population-of-origin. The study
      has discovered that very few people are needed to construct an "average" face,
      which is measurably indistinguishable from another average constructed using the
      faces of other people from within the group studied. This discovery has given the
      researchers confidence in the reliability of the archetypes which they have
      produced and this is important if such an analytical technique is to find
      application in discriminating between peoples on a population basis and in
      syndrome diagnosis.

PMID- 16563684
TI  - Guidelines in forensic odontology: legal aspects.
AB  - The task of the forensic dentist is ruled by an obligation to be diligent and
      prudent. If guidelines should exist which are recognised by the dental forensic
      community, they will probably be used to judge his work, even if guidelines are
      only considered as recommendations. The questions to be answered are: who issued
      these guidelines and are they conform to evidence-based forensic odontology.

PMID- 16563685
TI  - Characterisation and transfer of antibiotic resistance genes from enterococci
      isolated from food.
AB  - The genetic determinants responsible for the resistances against the antibiotics
      tetracycline [tet(M), tet(O), tet(S), tet(K) and tet(L)], erythromycin (ermA,B,C;
      mefA,E; msrA/B; and ereA,B) and chloramphenicol (cat) of 38 antibiotic-resistant
      Enterococcus faecium and Enterococcus faecalis strains from food were
      characterised. In addition, the transferability of resistance genes was also
      assessed using filter mating assays. The tet(L) determinant was the most commonly
      detected among tetracycline-resistant enterococci (94% of the strains), followed
      by the tet(M) gene, which occurred in 63.0% of the strains. Tet(K) occurred in
      56.0% of the resistant strains, while genes for tet(O) and tet(S) could not be
      detected. The integrase gene of the Tn916-1545 family of transposons was present
      in 81.3% of the tetracycline resistant strains, indicating that resistance genes
      might be transferable by transposons. All chloramphenicol-resistant strains
      carried a cat gene. 81.8% of the erythromycin-resistant strains carried the ermB
      gene. Two (9.5%) of the 21 erythromycin-resistant strains, which did not contain
      ermA,B,C, ereA,B and mphA genes harboured the msrC gene encoding an erythromycin
      efflux pump, which was confirmed by sequencing the PCR amplicon. In addition, all
      E. faecium strains contained the msrC gene, but none of the E. faecalis strains.
      Transfer of the genetic determinants for antibiotic resistance could only be
      demonstrated in one filter mating experiment, where both the tet(M) and tet(L)
      genes were transferred from E. faecalis FAIR-E 315 to the E. faecalis OG1X
      recipient strain. Our results show the presence of various types of resistance
      genes as well as transposon integrase genes associated with transferable
      resistances in enterococci, indicating a potential for gene transfer in the food
      environment.

PMID- 16563686
TI  - Molecular characterization of the alpha-glucosidase activity in Enterobacter
      sakazakii reveals the presence of a putative gene cluster for palatinose
      metabolism.
AB  - Enterobacter sakazakii is considered an opportunistic pathogen for premature
      infants and neonates. Although E. sakazakii has been isolated from various types
      of food, recontaminated dried infant formula has been epidemiologically
      identified as the major source of infection. Amongst others, alpha-glucosidase
      activity is one of the most important biochemical features, which differentiates
      E. sakazakii from other species in the family Enterobacteriaceae and has
      therefore been used as a selective marker in the development of differential
      media. However, it has been shown, that methods based on this biochemical feature
      are prone to producing false-positive results for presumptive E. sakazakii
      colonies due to the presence of this enzymatic activity in other species of the
      Enterobacteriaceae. Therefore, elucidation of the molecular basis responsible for
      the biochemical feature in E. sakazakii would provide novel targets suitable for
      the development of more specific and direct identification systems for this
      organism. By applying the bacterial artificial chromosome (BAC) approach, along
      with heterologous gene expression in Escherichia coli, the molecular basis of the
      alpha-glucosidase activity in E. sakazakii was characterized. Here we report the
      identification of two different alpha-glucosidase encoding genes. Homology
      searches of the deduced amino acid sequences revealed that the proteins belong to
      a cluster of gene products putatively responsible for the metabolism of
      isomaltulose (palatinose; 6-O-alpha-d-glucopyranosyl-d-fructose). The glycosyl
      hydrolyzing activity of each protein was demonstrated by subcloning the
      respective open reading frames and screening of E. coli transformants for their
      ability to hydrolyze 4-methyl-umbelliferyl-alpha-d-glucoside. Analysis at the
      protein level revealed that both enzymes belong to the intracellular fraction of
      cell proteins. The presence of the postulated palatinose metabolism was proven by
      growth experiments using this sugar as a sole carbon source.

PMID- 16563687
TI  - The stability of the amorphous form of cefuroxime axetil in solid state.
AB  - The stability of the amorphous form of cefuroxime axetil was studied by means of
      the stress stability test. The degradation was evaluated using the HPLC method
      with UV detection (278 nm), as described in the monograph of Cefuroxime Axetil in
      European Pharmacopoeia. Liquid chromatography was performed with a H5 SAS
      Hypersil column (5 microm particle size, 250 mmx4 mm), the mobile phase consisted
      of a mixture of 38 volumes of methanol and 62 volumes of a 23 g l-1 solution of
      ammonium dihydrogen phosphate, a flow rate of 1.2 ml min-1, and the internal
      standard was a solution of acetanilide in a mixture (1:1) of acetonitrile and
      water at a concentration of 0.2 mg ml-1. At an increased temperature at RH=0%,
      the degradation of cefuroxime axetil (CFA) diastereoisomers is the reversible
      first-order reaction, while that occurring in humid air (RH>25%) is the
      reversible first-order autocatalytic reaction with Delta3-isomers and E-isomers
      of cefuroxime axetil and cefuroxime as the main products.

PMID- 16563688
TI  - Development and validation of a specific stability indicating high performance
      liquid chromatographic method for rizatriptan benzoate.
AB  - A gradient, reversed-phase liquid chromatographic (RP-LC) method was developed
      for the quantitative determination of rizatriptan benzoate, used to treat
      relieves migraine headache symptoms. The developed method can be also employed
      for the related substance determination in bulk samples. Forced degradation
      studies were performed on bulk sample of rizatriptan benzoate using acid (0.5 N
      hydrochloric acid), base (0.1 N sodium hydroxide), oxidation (3.0% hydrogen
      peroxide), water hydrolysis, heat (60 degrees C) and photolytic degradation. Mild
      degradation of the drug substance was observed in base hydrolysis and
      considerable degradation observed during oxidative stress. The chromatographic
      method was fine tuned using the samples generated from forced degradation
      studies. Good resolution between the peaks corresponds to degradation products
      and the analyte was achieved on Agilent Zorbax SB-CN (250 mm x 4.6 mm, 5 microm)
      column. The mobile phase consists of a mixture of aqueous potassium di hydrogen
      ortho phosphate (pH 3.4), acetonitrile and methanol. The stress sample solutions
      were assayed against the qualified reference standard of rizatriptan benzoate and
      the mass balance in each case was close to 99.7% indicating that the developed
      method is stability indicating. Validation of the developed method was carried
      out as per ICH requirements.

PMID- 16563689
TI  - Quantitation of geometric isomers of a phosphodiesterase inhibitor in rat and
      monkey plasma using liquid chromatography-tandem mass spectrometry.
AB  - Quantitation of geometric isomers of a phosphodiesterase inhibitor was required
      to determine the extent of interconversion following dosing of a single isomer in
      preclinical pharmacokinetic studies. Assays were developed for the simultaneous
      determination of Compound A (Fig. 1), 6-[1-methyl-1-(methylsulfonyl)ethyl-8(3
      {(E)-2-(3-methyl-1,2,4-oxadiazol-5-yl)-2-[4
      (methylsulfonyl)phenyl]ethenyl}phenyl)quinoline] and its geometric Z-isomer,
      Compound B, in plasma using liquid chromatography-tandem mass spectrometry.
      Sample clean-up was performed using a semi-automated liquid-liquid extraction
      procedure. Separation was achieved on a Phenomenex Synergi MAX-RP column. The
      method was validated in the linear range of 2-2000 ng/mL for Compound A and 0.5
      500 ng/mL for Compound B in plasma and successfully applied to preclinical
      pharmacokinetic studies. Compound A was dosed in rats and Compound B in monkeys
      and the degree of conversion was determined by comparing the area under the
      curve. The relative amount of conversion was less than 1 and 10% in rats and
      monkeys, respectively. Because of the small amount of conversion and minor peak
      tailing of the dosed geometric isomer, the order of elution of the two analytes
      was important in order to achieve best quantitative results. The minor component
      needs to elute first; thus, a second assay was developed in which the order of
      elution was reversed. This was achieved by changing the mobile phase modifier.

PMID- 16563690
TI  - Validation of a levofloxacin HPLC assay in plasma and dialysate for
      pharmacokinetic studies.
AB  - An HPLC method with fluorescence detection suitable for routine determination of
      levofloxacin in plasma and dialysate has been validated. Sample preparation was
      assured by one-step protein precipitation for plasma or direct injection of the
      dialysate solution, respectively. Separation occurred on an YMC Pro C18 RP column
      (150 mm x 2 mm) with an acidic binary gradient mobile phase and detection at
      excitation and emission wavelengths of 296 and 504 nm. The assay was linear
      between 0.1 and 6 microg/ml for plasma and 0.1 and 5 microg/ml for dialysate with
      intra- and inter-day precision and accuracy lower than 10%. No degradation of
      levofloxacin was observed under the applied conditions for both matrices. The
      method was successfully applied to an in vitro pharmacokinetic study and patient
      samples as well.

PMID- 16563691
TI  - Effect of sterilization process on the formation of mono(2-ethylhexyl)phthalate
      from di(2-ethylhexyl)phthalate.
AB  - The risk assessment of di(2-ethylhexyl)phthalate (DEHP) migrating from polyvinyl
      chloride (PVC) medical devices is an important issue. Many studies have been
      conducted to determine the level of DEHP migration. A recent report has indicated
      that DEHP in blood bags is hydrolyzed by esterase into mono(2
      ethylhexyl)phthalate (MEHP). However, MEHP is thought to be even more toxic than
      the parent compound. Therefore, a method for the simultaneous determination of
      DEHP and MEHP was developed. The limits of quantification (LOQs) of DEHP and MEHP
      were 2.5 and 0.75 ng/ml, respectively. In this study, the effect of sterilization
      process on the levels of DEHP and MEHP migration was investigated. The level of
      migration of DEHP from gamma(gamma)-ray sterilized PVC sheet was low compared
      with that of the unsterilized control. By contrast, the level of MEHP migration
      from the gamma-ray sterilized PVC sheet was high compared with that of the
      unsterilized control. In addition, a high content of MEHP was found in the gamma
      ray sterilized PVC sheet.

PMID- 16563692
TI  - Father of 1-MCP.

PMID- 16563693
TI  - ERK1/2 activation attenuates TRAIL-induced apoptosis through the regulation of
      mitochondria-dependent pathway.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as an
      extracellular signal, which triggers apoptosis in tumor cells. In order to
      characterize the molecular events involved in TRAIL cytotoxic signaling, we
      attempted to determine the role of extracellular signal-regulated kinase 1/2
      (ERK1/2), as well as its downstream targets in TRAIL-treated HeLa cells. Here we
      demonstrate that TRAIL exposure resulted in the activation of ERK1/2, and the
      elevation of anti-apoptotic Bcl-2 protein levels. ERK1/2 inhibition with PD98059
      promoted cell death via the down-regulation of Bcl-2 protein levels, together
      with increasing mitochondrial damage, including the collapse of mitochondrial
      membrane potential, the release of cytochrome c from mitochondria to cytoplasm
      and caspase activity. These results suggest that the ERK1/2 activation is a kind
      of survival mechanism to struggle against TRAIL-induced stress condition in early
      stage, via activating cellular defense mechanisms like as the up-regulation of
      the Bcl-2/Bax ratio, as well as several mitochondrial events.

PMID- 16563694
TI  - P-glycoprotein in the placenta: expression, localization, regulation and
      function.
AB  - Detailed understanding of the mechanisms employed in transfer of drugs across the
      placenta is essential for optimization of pharmacotherapy during pregnancy.
      Disclosure of drug efflux transporters as an "active component" of the placental
      barrier has brought new important insights into the field of transplacental
      pharmacokinetics. P-glycoprotein (P-gp, MDR1) is the first discovered and so far
      the best characterized of drug efflux transporters, whose role in the regulation
      of drug disposition to the fetus has been extensively studied. Expression of P-gp
      in the placental trophoblast layer was confirmed at the mRNA and protein levels
      in all phases of pregnancy, and several in vitro and in vivo studies demonstrated
      functional activity of the transporter in materno-fetal drug transport. P-gp is
      able to actively pump drugs and other xenobiotics from trophoblast cells back to
      the maternal circulation, providing thus protection to the fetus. This review
      summarizes the current knowledge on the expression, localization and function of
      P-gp in the placenta. In addition, we include the latest data concerning
      transcriptional regulation of placental P-gp expression and polymorphisms of the
      MDR1 gene. Clinical significance of placental P-gp and its future perspectives
      for pharmacotherapy during pregnancy are also discussed.

PMID- 16563695
TI  - Real-time PCR detection and quantification of vector trichodorid nematodes and
      Tobacco rattle virus.
AB  - This report describes a novel diagnostic method for virus-vector trichodorid
      nematodes and associated Tobacco rattle virus (TRV) based on a real-time
      fluorogenic 5' nuclease PCR assay (TaqMan). Two independent primer/probe sets
      were designed targeting the 18S gene of the ribosomal cistron for the trichodorid
      species, Paratrichodorus pachydermus and Trichodorus similis. Assays using
      purified plasmid DNA containing clones of the 18S region and genomic DNA
      extracted from individuals from both nematode species displayed high specificity
      as no cros s-reaction was observed between the species or with two non-target
      trichodorid species Paratrichodorus anemones and Trichodorus primitivus. Relative
      quantification of target DNA present in unknown samples was performed by
      comparison of the fluorescence signals of the samples to those obtained from
      plasmid standard dilutions. Three primer/probe sets were also used to target TRV;
      one set for RNA1 and the two other sets for RNA2 of specific isolates (TRV-PpK20
      and TRV-TpO1). Detection of both trichodorid species and TRV RNA1 and RNA2 from a
      single sample was achieved and field samples were used to demonstrate the
      potential of this assay to provide rapid, accurate and sensitive molecular
      information in relation to risk assessment in the field.

PMID- 16563697
TI  - Correlation between glutathione peroxidase activity and anthropometrical
      parameters in adolescents with Down syndrome.
AB  - Since we have recently found that regular exercise increased erythrocyte
      antioxidant enzyme activities such as glutathione peroxidase (GPX) in adolescents
      with Down syndrome, these programs may be recommended. This study was designed to
      assess the role of anthropometrical parameters as easy, economic and non-invasive
      biomarkers of GPX. Thirty-one adolescents with Down syndrome performed a 12-week
      training program. Three days after its ending, GPX activity and anthropometrical
      parameters were assessed. Pearson's correlation coefficient showed negative but
      significant association (r=0.49, p=0.022) between GPX activity and waist
      circumference (WC). Body mass index (BMI) and waist-to-hip ratio (WHR) were not
      significant. We may conclude that anthropometrical parameters such as WC are easy
      to perform but not strongly associated to GPX activity. Further studies
      concerning other variables are needed.

PMID- 16563696
TI  - Species-specific identification by inhibitor-controlled PCR of ruminant
      components contaminating industrial crude porcine heparin.
AB  - With the emergence of bovine spongiform encephalopathy, the source of
      pharmaceutical heparin is currently restricted to porcine intestinal mucosa. To
      control the species origin of industrial crude heparin, molecular biology methods
      relying on species-specific protein or DNA analysis should be developed to
      identify the ruminant components that might be contaminants in industrial crude
      porcine heparin (ICPH). Because heparin contained in ICPH is a strong PCR
      inhibitory substance, it is necessary to explore DNA extraction methods specific
      for ICPH and develop analysis methods that could monitor the presence of PCR
      inhibitory substances. In the present studies, DNA was extracted from ICPH by
      seven methods, and their abilities to remove the PCR inhibitory substances were
      compared using inhibitory-controlled PCR (IC-PCR). The results showed that, based
      on the optimization of the final concentration of the internal processing control
      (IPC), IC-PCR was a rapid, sensitive and efficient way to monitor the presence of
      PCR inhibitory substances contained in DNA extracted from ICPH, and only the
      agarose gel purification method could be used to completely eliminate the PCR
      inhibitory substances contained in ICPH.

PMID- 16563698
TI  - Regulation of type II PIP kinase by PKD phosphorylation.
AB  - The type II PIP kinases phosphorylate the poorly understood inositol lipid
      PtdIns5P, producing the multi-functional lipid product PtdIns(4,5)P(2). To
      investigate the regulation of these enzymes by phosphorylation, we partially
      purified a protein kinase from pig platelets that phosphorylated type IIalpha PIP
      kinase on an activation loop threonine residue, T376. Pharmacological studies
      suggested this protein kinase was protein kinase D (PKD), and in vitro
      experiments confirmed this identification. A phospho-specific antibody was
      developed and used to demonstrate phosphorylation of T376 in living cells, and
      its enhancement under conditions in which PKD was activated. Although we were
      unable to determine the effects of phosphorylation on PIP kinase activity
      directly, mutation of T376 to aspartate significantly inhibited enzyme activity.
      We conclude that the type II PIP kinases are physiological targets for PKD
      phosphorylation, and that this modification is likely to regulate inositol lipid
      turnover by inhibition of these lipid kinases.

PMID- 16563700
TI  - Switch and maintenance of task set in schizophrenia.
AB  - Task set maintenance and switching deficits are robust in schizophrenia. However,
      little is known about how these constructs are related to one another. The
      development of an improved understanding of set switching and maintenance
      deficits in schizophrenia requires that these constructs be explicated in terms
      of elementary cognitive processes rather than grouped into broad psychological
      concepts like executive functioning. A relevant dichotomy has been proposed in
      which sensory and perceptual ("attentional") processes are distinguished from
      decisional ("intentional") processes in task maintenance and switching; however,
      the contributions these processes make to performance deficits in schizophrenia
      is not known. In the present study, 30 participants with schizophrenia and 27
      healthy comparisons completed a cued attentional set switching task. In addition
      to analyses of mean response times, the contributions of attentional and
      intentional processes to task performance were estimated using an ex-Gaussian
      distributional analysis. Schizophrenia was associated with a set maintenance
      deficit that was accounted for by an attentional, rather than intentional,
      dysfunction. Both groups showed significant switch costs that could be attributed
      to attentional processes, but there was no evidence for an attentional set
      switching deficit in schizophrenia. The findings suggest that set switching and
      set maintenance may reflect distinct cognitive deficits in schizophrenia and that
      they may be associated with unique information processing mechanisms.

PMID- 16563699
TI  - Neurocognitive performance and functional disability in the psychosis prodrome.
AB  - OBJECTIVE: This study evaluates the pattern of neuropsychological deficits and
      their association with clinical symptomatology and social functioning in
      individuals identified as ultra-high-risk (UHR) for psychosis. METHODS: A sample
      of 45 UHR individuals was identified using the Structured Interview for Prodromal
      Syndromes (SIPS) from consecutive referrals to the Staglin Music Festival Center
      for the Assessment and Prevention of Prodromal States (CAPPS) at UCLA.
      Participants were administered a neurocognitive test battery, as well as measures
      of global (Strauss-Carpenter Outcome Scale) and social functioning (UCLA Social
      Attainment Survey). RESULTS: Participants showed significant deficits in speed of
      processing, verbal learning and memory, and motor speed. Poorer verbal learning
      and memory performance was significantly associated with poorer social
      functioning, and there was a trend for poorer performance on reasoning and
      problem solving to be associated with poorer global functioning. Verbal memory
      independently predicted social functioning over and above severity of negative
      symptoms. Cognitive deficits were not associated with severity of clinical
      symptomatology. CONCLUSIONS: Despite the absence of fully psychotic symptoms, UHR
      individuals experience significant cognitive deficits, particularly on tasks
      requiring speeded information-processing and efficient recall from memory, and
      these deficits appear to be associated with functional disability in a manner
      parallel to that observed in patients with established psychotic illness.

PMID- 16563701
TI  - Population-based and family-based association studies of an (AC)n dinucleotide
      repeat in alpha-7 nicotinic receptor subunit gene and schizophrenia.
AB  - The human alpha-7 neuronal nicotinic receptor subunit (CHRNA7) gene, located at
      chromosome 15q13.2, represents a strong candidate gene for schizophrenia. We have
      examined an (AC)n dinucleotide repeat in intron 2 of the CHRNA7 gene, which was
      previously shown to be strongly linked with schizophrenia, using both population
      based and family-based association studies. In the population-based study, no
      significant differences between the genotype and allele frequency distributions
      in schizophrenia patients and control subjects were observed after correction for
      multiple testing, although a nominally significant association between the most
      common allele and schizophrenia was observed (P = 0.023, uncorrected for multiple
      testing). In the family-based study, there is no significant over-transmission
      (Transmitted/Non-transmitted: 61/50) of the same allele in 160 family trios.
      Overall, our results do not support a major role for the (AC)n dinucleotide
      repeat in schizophrenia susceptibility in Han Chinese. Further large-scale
      genetic studies based on a set of single nucleotide polymorphisms (SNPs) that
      fully characterize the linkage disequilibrium patterns at the CHRNA7 gene are
      necessary to determine the relevance of this gene as a risk factor for
      schizophrenia susceptibility.

PMID- 16563702
TI  - Response to Kujawa et al. letter-to-the-editor.

PMID- 16563703
TI  - Characterisation of a novel extended-spectrum beta-lactamase, SHV-70, from a
      clinical isolate of Enterobacter cloacae in China.

PMID- 16563704
TI  - Single-dose pharmacokinetics of cefodizime in critically ill elderly patients.
AB  - Cefodizime is an extended-spectrum third-generation cephalosporin antibiotic that
      is widely used in the treatment of severe infections of the respiratory and
      urinary tracts. Pharmacokinetic characteristics of cefodizime were assessed in 13
      critically ill elderly patients (median age 73+/-6 years). The mean cefodizime
      peak serum concentration following a single 2g cefodizime infusion was 219+/-58
      mg/L and the mean trough level 12 h after infusion was 29+/-17 mg/L. The
      elimination half-life was 6.19+/-2.45 h. Total body clearance, area under the
      plasma concentration-time curve and volume of distribution were 35.8+/-13.2
      mL/min, 1089.4+/-505.3 mg h/L and 17.4+/-6.3 L, respectively. Pharmacokinetics of
      cefodizime in critically ill elderly patients were comparable with those reported
      previously in healthy volunteers.

PMID- 16563705
TI  - Pharmacokinetics of cefepime in bile and gall bladder tissue after prophylactic
      administration in patients with extrahepatic biliary diseases.
AB  - The purpose of this study was to determine the cefepime concentrations in serum,
      bile and gall bladder tissue after administration of a single dose in patients
      with extrahepatic biliary diseases for pre-operative antimicrobial prophylaxis.
      During a 3-year period (1999-2002), 30 patients aged above 18 years with
      extrahepatic biliary diseases (acute and chronic cholecystitis and symptomatic
      cholelithiasis) were included in the study. Cefepime concentrations were
      determined by the agar microbiological diffusion method. A significant
      correlation between serum and gall bladder tissue concentrations of cefepime with
      the sampling interval was observed (r2 = 0.771, P<0.0001), whereas no correlation
      between serum and bile fluid concentrations of the drug was noted. In patients
      with non-functioning gall bladder, very low tissue levels of cefepime were
      detected. During the time of surgery, serum and gall bladder tissue
      concentrations of cefepime exceeded the minimum inhibitory concentration for 90%
      of the organisms (MIC90) for most common pathogens. Cefepime has the required
      pharmacokinetic properties to be considered for pre-operative antimicrobial
      prophylaxis in patients undergoing biliary tract surgery.

PMID- 16563706
TI  - Design of perfectly symmetric Trp-rich peptides with potent and broad-spectrum
      antimicrobial activities.
AB  - Tritrpticin, a member of the cathelicidin family, is a Trp-rich or Pro/Arg-rich
      peptide. Since the Trp, Pro and Arg residues are important in membrane disruption
      and/or cell entry, tritrpticin is a particularly attractive template around which
      to design novel antimicrobial peptides. Although tritrpticin is effective against
      a broad spectrum of microorganisms, it also has relatively strong haemolytic
      activity, which may compromise its therapeutic effects. To identify antimicrobial
      analogues of tritrpticin that lack cytotoxicity, we have designed and synthesised
      several molecules based on the amphipathic turn structure of tritrpticin. C
      terminal amidation of tritrpticin enhanced its antimicrobial activity, comparable
      with indolicidin, another Trp-rich peptide. In contrast, the additional insertion
      of positively-charged amino acids resulted in only small variations in antibiotic
      activity, suggesting that a total of five positive charges is sufficient for high
      antimicrobial activity. We found that perfectly symmetric analogues of
      tritrpticin with C-terminal amidation showed two- to eight-fold improved
      antimicrobial activity compared with tritrpticin, as well as significantly
      reduced haemolytic activity. This reduction in cytotoxicity was correlated with
      decreased permeabilization of the zwitterionic phosphatidylcholine membrane, the
      major component of the outer leaflet of red blood cells. In addition, we designed
      a symmetric indolicidin analogue that possessed antimicrobial potency and
      selectivity. Moreover, we found that these analogues of tritrpticin and
      indolicidin were effective against several antibiotic-resistant clinical
      bacterial isolates. Circular dichroism spectroscopy suggested that the structure
      of these symmetric analogues resembled that of tritrpticin or indolicidin in a
      membrane mimetic environment. Overall, our findings suggest that these symmetric
      peptides with an amphipathic turn structure may serve as useful templates for
      pharmaceutical compounds that may be effective against increasingly antibiotic
      resistant microbes.

PMID- 16563707
TI  - Clinical pharmacokinetics of voriconazole.
AB  - This review presents the published clinical pharmacokinetic data for the
      antifungal agent voriconazole. Aspects regarding absorption, tissue distribution,
      elimination and kinetic interactions are also discussed.

PMID- 16563708
TI  - [Effectiveness of an informative report on the prevention of nosocomial
      bloodstream infections in a neonatal intensive care unit].
AB  - OBJECTIVE: Few studies have evaluated the impact of an information and prevention
      process specifically aimed at neonatalogists and nurses working in a neonatal
      intensive care unit (NICU) towards the prophylaxis of nosocomial bloodstream
      infections. Our objective was first to analyze nosocomial infections within our
      unit, and secondly to evaluate the impact of a monthly report providing
      information related to the number and characteristics of such infections.
      PARTICIPANTS AND METHODS: A prospective study was performed in the NICU of Angers
      University Hospital during 2 six-month periods. All cases of nosocomial
      bloodstream infections and their characteristics were analyzed. We then published
      a nosocomial infections report every month during the second period, in order to
      inform the medical staff and nurses of the results. The impact of the information
      and prevention process was evaluated by comparing the results between the 2
      periods. We also assessed the staff's interest by questionnaire. RESULTS: Two
      hundred and fifty-four (first period) and 240 (second period) patients were
      included. A decrease in the specific incidence rate and density of catheter
      related bloodstream infections was observed between the 2 periods, especially for
      preterms with a birth weight<1000 g and gestational age<28 SA (P<0.01). Coagulase
      negative Staphylococcus was identified in 82.3% and 62.5% of cases respectively.
      54% of the members of staff expressed their concerns related to the findings and
      were very interested to read about the observations made during the study.
      CONCLUSION: This original process seems to be both effective and inexpensive, and
      can be easily reproduced to decrease the frequency of bloodstream infections in
      NICU. However, its long-term impact still needs to be evaluated.

PMID- 16563709
TI  - [Infantile anorexia: from birth to childhood].
AB  - Young child's anorexia (0-4 years) may have organic or psychological origin, when
      parents-child relationships are concerned. The most complex and earliest forms
      often have unspecified aetiology. Psychopathological classifications, which
      emphasize the mother-child relationships, are essential reference marks. But
      there is now a consensus in the definitions: the diagnosis of infantile anorexia
      requires criteria of acute or chronic malnutrition. We mainly distinguish
      anorexia by early disorder of homeostasis, anorexia resulting from serious
      disorder of attachment, anorexia by disorder of mother-child interactions, and
      finally early and complex anorexia, mixing an organic vulnerability and a bonding
      trouble, which can be secondary. Treatments differ according to the selected
      aetiology. Even if the origin is not mainly the fact of a relational mother-child
      dysfunction, parents-child's relations require a support to avoid aggravation by
      interactive vicious circles (force feeding). More than other diseases of early
      childhood, feeding disorders require a good knowledge of the working hypotheses
      both in the field of the paediatrics and the child psychiatry.

PMID- 16563710
TI  - [Causes of hospitalization of patients with ongoing varicella in a French
      children hospital: evolution between 1990 and 2001].
AB  - AIMS OF STUDY: To describe the characteristics of paediatric varicella in
      patients admitted through the emergency department (ED) of the Armand-Trousseau
      Children hospital in Paris and the evolution of the causes of admission during
      the study period. STUDY DESIGN: Retrospective longitudinal cohort study from
      March 1990 to February 2001. RESULTS: One hundred and eight children were
      hospitalized for varicella during these 11 years. Sixty per cent were under 2
      years of age and all but one were immunocompetent. The first cause of admission
      was the presence of at least 1 complication (83,3%) classified as: cutaneous
      (34%), digestive (19,8,%), respiratory (17,6%), neurological (15,3%) and ENT
      complications (8,8%). Over 11 years, the rate of overall complications remained
      stable but there was an important increase in varicella cases admitted through
      the ED mainly due to increase in cutaneous superinfections. CONCLUSION: These
      data confirm the potential severity of varicella and underline the emerging
      problem of increasing cutaneous complications. Additional studies are necessary
      to address this phenomenon and to determine optimal prophylactic measures.

PMID- 16563711
TI  - Diversity of the fatty acids of the Nostoc species and their statistical
      analysis.
AB  - Low molecular, hydroxy, dioic, saturated and unsaturated fatty acids were
      determined of six cyanobacterial species belonging to genus Nostoc and in
      different habitats: freshwater, terrestrial, and as well as symbionts. There are
      large variations in individual fatty acid contents according to species, and
      location of the genus Nostoc. Statistical analysis of variability of fatty acids
      belonging to the genus Nostoc is reported.

PMID- 16563712
TI  - DNA buoyant density shifts during 15N-DNA stable isotope probing.
AB  - DNA-based stable isotope probing (SIP) is a novel technique for the
      identification of organisms actively assimilating isotopically labeled compounds.
      Herein, we define the limitations to using 15N-labeled substrates for SIP and
      propose modifications to compensate for these shortcomings. Changes in DNA
      buoyant density (BD) resulting from 15N incorporation were determined using
      cultures of disparate GC content (Escherichia coli and Micrococcus luteus).
      Incorporation of 15N into DNA increased BD by 0.015+/-0.002 g mL(-1) for E. coli
      and 0.013+/-0.002 g mL(-1) for M. luteus. The DNA BD shift was greatly increased
      (0.045 g mL(-1)) when dual isotope (13C plus 15N) labeling was employed. Despite
      the limited DNA BD shift following 15N enrichment, we found the use of gradient
      fractionation, followed by a comparison of T-RFLP profiles from fractions of
      labeled and control treatments, facilitated detection of enrichment in DNA
      samples from either cultures or soil.

PMID- 16563713
TI  - Detection and quantification of phnE gene from oil-contaminated soil samples by
      competitive quantitative PCR.
AB  - The phnE gene encoding catechol 2,3-dioxygenase belonging to the meta-cleavage
      pathway was selected as the marker gene and was detected and quantified from soil
      samples by competitive quantitative PCR. A PCR primer pair was designed based on
      the phnE gene to amplify the target DNA bands and competitor DNA bands. The phnE
      gene was detected in two samples of three. In samples S1 and S2, the phnE gene
      copy number was 6.2 x 10(7)/g soil and 5.8 x 10(7)/g soil, respectively. But no
      phnE gene was detected in sample S3. The target DNA bands were extracted and
      expressed. The results confirmed that the target DNA bands were the native phnE
      genes.

PMID- 16563714
TI  - Analysis of Claviceps africana and C. sorghi from India using AFLPs, EF-1alpha
      gene intron 4, and beta-tubulin gene intron 3.
AB  - Isolates of Claviceps causing ergot on sorghum in India were analysed by AFLP
      analysis, and by analysis of DNA sequences of the EF-1alpha gene intron 4 and
      beta-tubulin gene intron 3 region. Of 89 isolates assayed from six states in
      India, four were determined to be C. sorghi, and the rest C. africana. A
      relatively low level of genetic diversity was observed within the Indian C.
      africana population. No evidence of genetic exchange between C. africana and C.
      sorghi was observed in either AFLP or DNA sequence analysis. Phylogenetic
      analysis was conducted using DNA sequences from 14 different Claviceps species. A
      multigene phylogeny based on the EF-1alpha gene intron 4, the beta-tubulin gene
      intron 3 region, and rDNA showed that C. sorghi grouped most closely with C.
      gigantea and C. africana. Although the Claviceps species we analysed were closely
      related, they colonize hosts that are taxonomically very distinct suggesting that
      there is no direct coevolution of Claviceps with its hosts.

PMID- 16563715
TI  - Determinants of the bronchodilation response to salbutamol on histamine-induced
      bronchoconstriction.
AB  - Assessment of the bronchodilation response to short-acting beta2-adrenoreceptor
      agonists on pharmacologically induced bronchoconstriction has often been used to
      investigate airway smooth muscle beta2-adrenoreceptor function. However, little
      is known about factors affecting this response. In the present study, the
      bronchodilation response to 0.2 mg of salbutamol on histamine-induced
      bronchoconstriction was assessed in 101 steroid-naive asthmatic subjects. The
      associations of the response with a wide range of challenge procedure-related
      variables, clinical asthma severity indicators, and blood markers of airway
      inflammation were investigated. The response was re-assessed after 6 and 12
      weeks' therapy with inhaled budesonide. Baseline FEV1, final histamine
      concentration, and the maximal fall in FEV1 explained 35-59% of the total
      variation in the response to salbutamol, depending on the index chosen to express
      the response. Serum concentration of myeloperoxidase, an index of neutrophilic
      inflammation, was associated with a poor response. The preceding week daily PEF
      variation, rescue bronchodilator use, severity of asthmatic symptoms, blood
      eosinophil count, and serum eosinophilic cationic protein and eosinophilic
      protein X concentrations were not associated with the response. The salbutamol
      response seemed to diminish during budesonide treatment but when adjusted by the
      challenge procedure-related variables the treatment effect vanished. In
      conclusion, the bronchodilation response to salbutamol on histamine-induced
      bronchoconstriction is largely determined by challenge procedure-related
      variables. It seems to be unrelated to the clinical severity of asthma and is not
      affected by treatment with inhaled corticosteroids. Neutrophilic airway
      inflammation may be associated with a poor response.

PMID- 16563716
TI  - Different ratios of eicosapentaenoic and docosahexaenoic omega-3 fatty acids in
      commercial fish oils differentially alter pro-inflammatory cytokines in
      peritoneal macrophages from C57BL/6 female mice.
AB  - The use of fish oil (FO) as a dietary supplement to prevent or reduce the
      severity of cardiovascular diseases and autoimmune disorders such as rheumatoid
      arthritis is receiving much attention. Several recent reports indicate that
      eating fish often or the use of small doses of FO capsules appears to have
      benefits against cardiovascular diseases. We have reported in the past that diets
      enriched with FO protect against renal diseases and prolong the life span of
      autoimmune-prone mice compared to corn oil (CO) diets. However, the optimum ratio
      of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) in commercially
      available FOs to reduce the production of various pro-inflammatory cytokines has
      not been well established. We, therefore, obtained deodorized FO from three
      sources containing different EPA/DHA contents, fed them to C57BL/6 mice for 8
      weeks in a 10% (vol/wt) diet (oil A, 11/10; oil B, 14/9; oil C, 23/14) and
      compared them with (10%) CO-fed mice as control. TNF-alpha, IL-6 and IL-1beta
      were measured by enzyme-linked immunosorbent assay in thioglycollate-induced
      macrophages, 8 and 24 h after lipopolysaccharide treatment. The results showed a
      significant decrease in TNF-alpha after only 8 h in oil C. After 24 h, TNF-alpha,
      IL-6 and IL-1beta levels decreased only in mice fed oil C, although
      nonsignificant decreases were seen in mice fed oil A compared to mice fed CO. The
      antioxidant enzymes, catalase and glutathione transferase, were higher in kidneys
      of mice fed oil C compared to mice fed CO. The study suggests that anti
      inflammatory activity may vary among different sources of FO due to variations in
      EPA/DHA content.

PMID- 16563717
TI  - Carotenoids enhance phosphorylation of Akt and suppress tissue factor activity in
      human endothelial cells.
AB  - Enhanced production of tissue factor has been linked to development of
      cardiovascular disease due to endothelial activation, resulting in thrombosis of
      blood vessels. Epidemiological studies reported that diet-derived antioxidants
      might suppress and/or delay progression of cardiovascular disease. Detailed
      molecular level studies are needed to understand this effect with prevention as a
      goal. Water-dispersible forms of various carotenoids (beta-carotene, lutein and
      lycopene) from natural sources in microemulsion were used to study effects of
      carotenoids on tissue factor activity in human endothelial cells. All carotenoids
      studied suppressed tissue factor activity (P<.01) and gene expression in human
      endothelial cells. Our study also demonstrated that addition of Akt-specific
      inhibitor reversed the inhibitory effect of carotenoids on tissue factor
      activity, indicating that carotenoids enhanced phosphorylation of Akt and
      suppressed tissue factor activity in endothelial cells by this mechanism.

PMID- 16563718
TI  - Linoleic acid induces proinflammatory events in vascular endothelial cells via
      activation of PI3K/Akt and ERK1/2 signaling.
AB  - Linoleic acid (18:2n-6), is a major unsaturated fatty acid in the American diet.
      Linoleic acid is considered to be atherogenic because of its pro-oxidative and
      proinflammatory properties. There is substantial evidence that linoleic acid (LA)
      can activate vascular endothelial cells and contribute to an inflammatory
      response. To explore the mechanisms of LA-induced proinflammatory signaling
      pathways, the present study addresses the role of the phosphatidylinositol 3
      kinase/amino kinase terminal (PI3K/Akt), extracellular signal regulated kinase
      1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways during
      vascular endothelial cell activation. After a 3- to 6-h exposure, LA
      significantly activated both Akt and ERK in endothelial cells, as assessed by
      western blot and immunofluorescence. In contrast, LA activated p38 MAPK already
      at 10 min, suggesting that p38 MAPK signaling occurred upstream of the ERK1/2
      pathway. Furthermore, inhibition of ERK activity by PD98059 and PI3K/Akt activity
      by LY294002 or wortmannin significantly reduced the LA-induced activation of
      nuclear factor kappa B (NF-kappaB). These results suggest a contribution of both
      the ERK1/2 and PI3K/Akt pathways to the effect of LA on NF-kappaB-dependent
      transcription. Indeed, LA-mediated gene expression of the vascular cell adhesion
      molecule 1 was suppressed by PD98059, wortmannin and LY294002. These data
      indicate that both PI3K/Akt- and ERK1/2-mediated proinflammatory signaling events
      are critical in LA-induced endothelial cell activation and vascular inflammation.

PMID- 16563719
TI  - One-year soy isoflavone supplementation prevents early postmenopausal bone loss
      but without a dose-dependent effect.
AB  - It is believed that soy isoflavone has much potential effectiveness on the
      postmenopausal status; however, the optimal dose for preventing postmenopausal
      bone loss still remains unclear. This open-labeled, self-controlled pilot study
      was undertaken to determine the effect of 1-year supplementation of different
      high dosages of soy isoflavone in postmenopausal Taiwanese women. Forty-three
      women aged 45-67 years were enrolled and randomly assigned into a control (C),
      100 mg/day isoflavone (IF100) and 200 mg/day isoflavone (IF200) groups for 1
      year. Dual-energy X-ray absorptiometry and other related biochemical markers of
      bone metabolism were measured. Results indicated that the decrease in bone
      mineral density (BMD) was significant for lumbar vertebrae L1-3, L1-4 and the
      femur neck in the C group; surprisingly, the BMD of L1-3 was significantly
      elevated in the IF100 group; however, there were no consistent responses in the
      IF200 group. No significant change except loss of the bone mineral content of
      Ward's triangle (P=.003) was found in the IF200 group after treatment. The
      percentage change at L1-3 was less (P=.04) in the IF200 group when compared to
      the IF100 group. A relatively uniform direction of bone formation in expanding
      the weight and area with different rates of change resulted in different BMD
      changes. Both indicated a change of bone formation patterns with the higher-dose
      supplement. A protective effect of IF100 on estrogen-related bone loss was
      observed. A lack of a benefit such as high safety in the IF200 group for 1-year
      administration was ensured and lacked undesirable side effects.

PMID- 16563720
TI  - Purification and characterization of antioxidant peptide from hoki (Johnius
      belengerii) frame protein by gastrointestinal digestion.
AB  - To extract antioxidant peptide from hoki frame protein hydrolysate (APHPH), we
      employed six proteases (pepsin, trypsin, papain, alpha-chymotrypsin, Alcalase and
      Neutrase) for enzymatic hydrolysis, and the antioxidant activities of their
      hydrolysates were investigated using both lipid peroxidation inhibition assay and
      free radical scavenging assay by electron spin resonance spin-trapping technique.
      Among hydrolysates, peptic hydrolysate, having the highest antioxidant activity,
      further separated into four groups using ultrafiltration membranes and purified
      consecutive chromatographic methods. Finally, the purified peptide had a
      molecular mass of 1801 Da, and amino acid sequence was identified as Glu-Ser-Thr
      Val-Pro-Glu-Arg-Thr-His-Pro-Ala-Cys-Pro-Asp-Phe-Asn. APHPH inhibited lipid
      peroxidation higher than that of alpha-tocopherol as positive control and
      efficiently quenched different sources of free radical: 1,1-diphenyl-2-pycryl
      hydrazyl (IC(50)=41.37 microM), hydroxyl (IC(50)=17.77 microM), peroxyl
      (IC(50)=18.99 microM) and superoxide radicals (IC(50)=172.10 microM).
      Furthermore, APHPH decreased t-butylhydroperoxide-induced cytotoxicity on human
      embryonic lung fibroblasts and efficiently protected free-radical-induced DNA
      damage.

PMID- 16563721
TI  - Effect of glutamine on glutathione kinetics in vivo in dogs.
AB  - To determine whether glutamine affects glutathione (GSH, gamma-glutamyl-cysteinyl
      glycine) metabolism, seven healthy beagle dogs received 6-h infusions of
      [(15)N]glutamate and [(13)C]leucine after a 3-day fast. Isotope infusions were
      performed during oral feeding with an elemental regimen, supplemented with either
      l-glutamine or an isonitrogenous amino acid mixture, on two separate days and in
      randomized order. Timed blood samples were obtained, and a surgical duodenal
      biopsy was performed after 6 h of isotope infusion. GSH fractional synthesis rate
      (FSR) was assessed from [(15)N]glutamate incorporation into blood and gut GSH,
      and duodenal protein synthesis from [(13)C]leucine incorporation into gut
      protein. Glutamine supplementation failed to alter erythrocyte GSH concentration
      (2189+/-86 vs. 1994+/-102 micromol L(-1) for glutamine vs. control; ns) or FSR
      (64+/-17% vs. 74+/-20% day(-1); ns). In the duodenum, glutamine supplementation
      was associated with a 92% rise in reduced/oxidized GSH ratio (P=.024) and with a
      44% decline in GSH FSR (96+/-15% day(-1) vs. 170+/-18% day(-1); P=.005), whereas
      total GSH concentration remained unchanged (808+/-154 vs. 740+/-127 micromol kg(
      1); P=.779). We conclude that, in dogs receiving enteral nutrition after a 3-day
      fast: (1) glutamine availability does not affect blood GSH, and, (2) in contrast,
      in the duodenum, the preserved GSH pool, along with a decreased synthesis rate,
      suggests that glutamine may maintain GSH pool and intestinal redox status by
      acutely decreasing GSH utilization.

PMID- 16563722
TI  - Potent inhibitory effect of trans9, trans11 isomer of conjugated linoleic acid on
      the growth of human colon cancer cells.
AB  - This study compared the growth inhibitory effects of pure conjugated linoleic
      acid (CLA) isomers [cis(c)9,c11-CLA, c9,trans(t)11-CLA, t9,t11-CLA, and t10,c12
      CLA] on human colon cancer cell lines (Caco-2, HT-29 and DLD-1). When Caco-2
      cells were incubated up to 72 h with 200 microM, each isomer, even in the
      presence of 10% fetal bovine serum (FBS), cell proliferation was inhibited by all
      CLA isomers in a time-dependent manner. The strongest inhibitory effect was shown
      by t9,t11-CLA, followed by t10,c12-CLA, c9,c11-CLA and c9,t11-CLA, respectively.
      The strongest effect of t9,t11-CLA was also observed in other colon cancer cell
      lines (HT-29 and DLD-1). The order of the inhibitory effect of CLA isomer was
      confirmed in the presence of 1% FBS. CLA isomers supplemented in the culture
      medium were readily incorporated into the cellular lipids of Caco-2 and changed
      their fatty acid composition. The CLA contents in cellular lipids were 26.2+/
      2.7% for t9,t11-CLA, 35.9+/-0.3% for c9,t11-CLA and 46.3+/-0.8% for t10,c12-CLA,
      respectively. DNA fragmentation was clearly recognized in Caco-2 cells treated
      with t9,t11-CLA. This apoptotic effect of t9,t11-CLA was dose- and time
      dependent. DNA fragmentation was also induced by 9c,11t-CLA and t10,c12-CLA.
      However, fragmentation levels with both isomers were much lower than that with
      t9,t11-CLA. t9t11-CLA treatment of Caco-2 cells decreased Bcl-2 levels in
      association with apoptosis, whereas Bax levels remained unchanged. These results
      suggest that decreased expression of Bcl-2 by t9t11-CLA might increase the
      sensitivity of cells to lipid peroxidation and to programmed cell death,
      apoptosis.

PMID- 16563723
TI  - Phenylethyl isothiocyanate and its N-acetylcysteine conjugate suppress the
      metastasis of SK-Hep1 human hepatoma cells.
AB  - Phenylethyl isothiocyanate (PEITC), a hydrolysis compound of gluconasturtiin, is
      metabolized to N-acetylcysteine (NAC)-PEITC in the body after the consumption of
      cruciferous vegetables. We observed an inhibitory effect of PEITC and its
      metabolite NAC-PEITC on cancer cell proliferation, adhesion, invasion, migration
      and metastasis in SK-Hep1 human hepatoma cells. PEITC and NAC-PEITC suppressed SK
      Hep1 cell proliferation in a dose-dependent manner, and exposure to 10 microM
      PEITC or NAC-PEITC reduced cell proliferation by 25% and 30%, respectively. NAC
      PEITC inhibited cancer cell adhesion, invasion and migration to a similar or to
      an even larger degree than PEITC. The expression of matrix metalloproteinase
      (MMP) 2, MMP-9 and membrane type 1 matrix metalloproteinase (MT1-MMP) is a known
      risk factor for metastatic disease. Gelatin zymography analysis revealed a
      significant downregulation of MMP-2/MMP-9 protein expression in SK-Hep1 cells
      treated with 0.1-5 microM PEITC or NAC-PEITC. PEITC and NAC-PEITC treatment
      caused dose-dependent decreases in MMP-2/MMP-9 and MT1-MMP mRNA levels, as
      determined by reverse transcription polymerase chain reaction. PEITC and NAC
      PEITC also increased the mRNA levels of tissue inhibitors of matrix
      metalloproteinase (TIMPs) 1 and 2. Our data suggest that this inhibition is
      mediated by downregulation of MMP and upregulation of TIMPs.

PMID- 16563724
TI  - Cytoskeletal scaffolds regulate riboflavin endocytosis and recycling in placental
      trophoblasts.
AB  - Microfilaments and microtubules (MT) play a vital role in cellular endocytic
      processes. The present study evaluates the role of these cytoskeletal elements in
      the apical internalization and postendocytic fate of riboflavin (RF) in placental
      trophoblasts (BeWo cells). Biochemical modification of the actin and microtubule
      network by (1) okadaic acid (OA), which disrupts MT-based vesicular trafficking;
      (2) cytochalasin D and latrunculin B, which promote actin depolymerization; and
      (3) 2,3-butanedione monoxime (BDM), which inhibits myosin-actin interaction, was
      confirmed by immunofluorescence microscopy using actin- and tubulin-specific
      antibodies. Furthermore, involvement of the molecular motors dynein and kinesin
      was assessed in the presence of (1) sodium orthovanadate, which inhibits dynein
      ATPase activity and (2) adenosine 5'-(beta,gamma-imido)triphosphate tetralithium
      salt hydrate, a non-hydrolyzable ATP analog, which results in defective kinesin
      driven processes. RF internalization consequent to cytoskeletal alterations was
      compared with that of a clathrin-dependent endocytic marker ([125I]-transferrin
      [TF]), a caveolae-mediated endocytic substrate ([3H]-folic acid [FA]), and a
      fluid-phase endocytic marker ([125I]-horse radish peroxidase [HRP]). Apical
      recycling and bidirectional transport of RF and TF was measured following
      cytoskeletal alterations. Results indicate that uptake of RF, TF, FA and HRP are
      markedly reduced (approximately 30-65%) in the presence OA and BDM, suggesting
      differential sensitivities to modification of kinesin-driven microtubules.
      However, actin depolymerization negatively affected HRP endocytosis alone, while
      RF, FA and TF internalization remained unchanged. Disturbances in protein
      phosphorylation cascades also influenced apical recycling while net ligand
      transport across monolayers remained unaffected. In conclusion, apical RF
      trafficking in placental cells is tightly regulated by microtubules and supported
      by accessory actin involvement.

PMID- 16563725
TI  - Dietary carbohydrate and cholesterol influence the number of particles and
      distributions of lipoprotein subfractions in guinea pigs.
AB  - Guinea pigs (n=10/group) were fed one of three diets: a high carbohydrate (CHO)
      (42% energy), low cholesterol (0.04%) diet (LChHC), a diet with the same amount
      of CHO but with 0.25% cholesterol (HChHC) or a diet with 11% of energy from CHO
      and 0.25% cholesterol (HChLC) for 12 weeks. VLDL- and LDL cholesterol (LDL-C)
      were higher in the HChLC and HChHC groups than in the LChHC group (P<.0001).
      Lipoprotein subclasses and size were analyzed by nuclear magnetic resonance.
      Dietary cholesterol (HChHC and HChLC groups) resulted in larger VLDL particles
      (71.1+/-6.9, 78.9+/-3.33 nm, respectively) than those in the LChHC group (44.3+/
      10.8 nm). In addition, there were higher concentrations of the large VLDL (>60
      nm) and the medium VLDL (>35 nm) in the high cholesterol groups (P<.01).
      Similarly, the concentration of the medium (>8.2 nm) and small HDL (>7.2 nm) was
      higher in the HChHC and HChLC groups (P<.001). In contrast, CHO restriction
      affected the concentrations of LDL subfractions. The number of total LDL
      particles was lower in the HChLC (291.3+/-85.0 nmol/L) than in the HChHC group
      (467.6+/-113.1 nmol/L), indicating that the cholesterol in LDL was distributed in
      less particles in the former group. The concentrations of medium LDL (>19.8 nm)
      (98.4+/-90.8) and small LDL (>18 nm) (29.3+/-24.9 nmol/L) were lower in the HChLC
      group than in the HChHC group (261.8+/-105.8 and 64.9+/-27.9 nmol/L,
      respectively). These results indicate that dietary cholesterol increased the
      atherogenicity of both VLDL and HDL while CHO restriction increased the number of
      large LDL and decreased the concentrations of the more atherogenic smaller LDL
      subfractions.

PMID- 16563726
TI  - Vanadium recovery from oil fly ash by leaching, precipitation and solvent
      extraction processes.
AB  - In order to reduce the environmental impact due to land disposal of oil fly ash
      from power plants and to valorize this waste material, the removal of vanadium
      was investigated using leaching processes (acidic and alkaline treatments),
      followed by a second step of metal recovery from leachates involving either
      solvent extraction or selective precipitation. Despite a lower leaching
      efficiency (compared to sulfuric acid), sodium hydroxide was selected for
      vanadium leaching since it is more selective for vanadium (versus other
      transition metals). Precipitation was preferred to solvent extraction for the
      second step in the treatment since: (a) it is more selective; enabling complete
      recovery of vanadate from the leachate in the form of pure ammonium vanadate; and
      (b) stripping of the loaded organic phase (in the solvent extraction process) was
      not efficient. Precipitation was performed in a two-step procedure: (a) aluminum
      was first precipitated at pH 8; (b) then ammonium chloride was added at pH 5 to
      bring about vanadium precipitation.

PMID- 16563727
TI  - Hydro-mechanical behavior of municipal solid waste subject to leachate
      recirculation in a large-scale compression reactor cell.
AB  - The paper presents the results of a laboratory experiment on Municipal Solid
      Waste (MSW) subjected to one-dimensional compression in a 1 m3 instrumented cell.
      The focus was on the hydro-mechanical behavior of the material under conditions
      of confinement and leachate percolation that replicate those found in real-scale
      landfills. The operation of the apparatus is detailed together with the testing
      methodology and the monitoring program. Two samples of waste were tested: the
      first extended over a period of 10 months ('Control Test') and the second for 22
      months ('Enhanced Test' with leachate recirculation). Consolidation data is
      reported with regard to both short-term (stress-dependent) and long-term (time
      dependent) settlements. A discussion follows based on the derived values of
      primary and secondary compression ratios. Correlations between compression
      parameters and the biodegradation process are presented. In particular, results
      clearly highlight the effect of leachate recirculation on waste settlement: 24%
      secondary deformation reached after slightly less than 2 years (equivalent to a 5
      fold increase in compressibility) and 17.9% loss of dry matter. Comparisons are
      proposed considering the results derived from the few monitoring programs
      conducted on experimental bioreactors worldwide. Finally, the hydraulic
      characterization of waste is discussed with regard to the evaluation of effective
      porosity and permeability.

PMID- 16563728
TI  - Nanocrystalline diamond modified gold electrode for glucose biosensing.
AB  - Boron-doped diamond has drawn much attention in electrochemical sensors. However
      there are few reports on non-doped diamond because of its weak conductivity.
      Here, we reported a glucose biosensor based on electrochemical pretreatment of
      non-doped nanocrystalline diamond (N-NCD) modified gold electrode for the
      selective detection of glucose. N-NCD was coated on gold electrode and glucose
      oxidase (GOx) was immobilized onto the surfaces of N-NCD by forming amide
      linkages between enzyme amine residues and carboxylic acid groups on N-NCD. The
      anodic pretreatment of N-NCD modified electrode not only promoted the electron
      transfer rate in the N-NCD thin film, but also resulted in a dramatic improvement
      in the reduction of the dissolved oxygen. This performance could be used to
      detect glucose at negative potential through monitoring the current change of
      oxygen reduction. The biosensor effectively performs a selective electrochemical
      analysis of glucose in the presence of common interferents, such as ascorbic acid
      (AA), acetaminophen (AP) and uric acid (UA). A wide linear calibration range from
      10 microM to 15 mM and a low detection limit of 5 microM were achieved for the
      detection of glucose.

PMID- 16563729
TI  - The neurobiology of visual attention: finding sources.
AB  - The profusion of progress during the past twenty years in identifying neural
      correlates of selective attention within the visual system has left open the
      question of how visual representations are biased to favor target stimuli.
      Studies aimed at specifying the mechanisms that can be causally implicated in the
      control of visual selective attention have only recently begun in earnest.
      Employing both the psychophysical and the neuroanatomical data, recent
      neurophysiological experiments in monkeys and neuroimaging studies in humans are
      converging on the neural circuits that provide the source of at least some forms
      of attentional control signals.

PMID- 16563730
TI  - Reconsolidation: the advantage of being refocused.
AB  - Ample evidence suggests that upon their retrieval, items in long-term memory
      enter a transient special state, in which they might become prone to change. The
      process that generates this state is dubbed 'reconsolidation'. The dominant
      conceptual framework in this revitalized field of memory research focuses on
      whether reconsolidation resembles consolidation, which is the process that
      converts an unstable short-term memory trace into a more stable long-term trace.
      However, this emphasis on the comparison of reconsolidation to consolidation
      deserves reassessment. Instead, the phenomenon of reconsolidation, irrespective
      of its relevance to consolidation, provides a unique opportunity to tap into the
      molecular, cellular and circuit correlates of memory persistence and retrieval,
      of which we currently know only little.

PMID- 16563731
TI  - Cognitive neuroscience and the law.
AB  - Advances in cognitive neuroscience now allow us to use physiological techniques
      to measure and assess mental states under a growing set of circumstances. The
      implication of this growing ability has not been lost on the western legal
      community. If biologists can accurately measure mental state, then legal
      conflicts that turn on the true mental states of individuals might well be
      resolvable with techniques ranging from electroencephalography to functional
      magnetic resonance imaging. Therefore, legal practitioners have increasingly
      sought to employ cognitive neuroscientific methods and data as evidence to
      influence legal proceedings. This poses a risk, because these scientific
      methodologies have largely been designed and validated for experimental use only.
      Their subsequent use in legal proceedings is an application for which they were
      not intended, and for which those methods are inadequately tested. We propose
      that neurobiologists, who might inadvertently contribute to this situation,
      should be aware of how their papers will be read by the legal community and
      should play a more active role in educating and engaging with that community.

PMID- 16563732
TI  - Generalist genes and cognitive neuroscience.
AB  - Multivariate genetic research suggests that a single set of genes affects most
      cognitive abilities and disabilities. This finding already has far-reaching
      implications for cognitive neuroscience, and will become even more revealing when
      this - presumably large - set of generalist genes is identified. Similar to other
      complex disorders and dimensions, molecular genetic research on cognitive
      abilities and disabilities is adopting genome-wide association strategies. These
      strategies involve very large samples to detect DNA associations of small effect
      size using microarrays that simultaneously assess hundreds of thousands of DNA
      markers. When this set of generalist genes is identified, it can be used to
      provide solid footholds in the climb towards a systems-level understanding of how
      genetically driven brain processes work together to affect diverse cognitive
      abilities and disabilities.

PMID- 16563734
TI  - Cortical control of motor sequences.
AB  - The neural substrate of sequence learning is well known. However, we lack a clear
      understanding of the detailed functional properties of many of the areas
      involved. The reason for this discrepancy lies, in part, in the fact that two
      types of processes, implicit and explicit, subserve motor sequence learning, and
      these often interact with each other. The most significant recent advances have
      been the elucidation of the very complex relationships between medial motor areas
      and the temporal and ordinal control of sequences, and the demonstration that
      motor cortex is an important site for sequence storage and production. The
      challenge for the future will be to develop a coherent and internally consistent
      theory of sequence control.

PMID- 16563735
TI  - Human parietal cortex in action.
AB  - Experiments using functional neuroimaging and transcranial magnetic stimulation
      in humans have revealed regions of the parietal lobes that are specialized for
      particular visuomotor actions, such as reaching, grasping and eye movements. In
      addition, the human parietal cortex is recruited by processing and perception of
      action-related information, even when no overt action occurs. Such information
      can include object shape and orientation, knowledge about how tools are employed
      and the understanding of actions made by other individuals. We review the known
      subregions of the human posterior parietal cortex and the principles behind their
      organization.

PMID- 16563736
TI  - Learning and neural plasticity in visual object recognition.
AB  - The capability of the adult primate visual system for rapid and accurate
      recognition of targets in cluttered, natural scenes far surpasses the abilities
      of state-of-the-art artificial vision systems. Understanding this capability
      remains a fundamental challenge in visual neuroscience. Recent experimental
      evidence suggests that adaptive coding strategies facilitated by underlying
      neural plasticity enable the adult brain to learn from visual experience and
      shape its ability to integrate and recognize coherent visual objects.

PMID- 16563737
TI  - The computational neurobiology of learning and reward.
AB  - Following the suggestion that midbrain dopaminergic neurons encode a signal,
      known as a 'reward prediction error', used by artificial intelligence algorithms
      for learning to choose advantageous actions, the study of the neural substrates
      for reward-based learning has been strongly influenced by computational theories.
      In recent work, such theories have been increasingly integrated into experimental
      design and analysis. Such hybrid approaches have offered detailed new insights
      into the function of a number of brain areas, especially the cortex and basal
      ganglia. In part this is because these approaches enable the study of neural
      correlates of subjective factors (such as a participant's beliefs about the
      reward to be received for performing some action) that the computational theories
      purport to quantify.

PMID- 16563738
TI  - Developmental prosopagnosia: a window to content-specific face processing.
AB  - Developmental prosopagnosia is characterized by severely impaired face
      recognition. Individuals with this disorder, which often runs in families, have
      no history of brain damage and intact early visual processing systems. Recent
      research has also demonstrated that many developmental prosopagnosics have normal
      or relatively good object recognition, indicating that their impairments are not
      the result of deficits to a unitary visual recognition mechanism. To investigate
      the nature of the impaired mechanisms, extensive testing was done on an
      individual with especially pure face processing deficits. The results ruled out
      all extant explanations of prosopagnosia except one that proposed that faces are
      recognized by a content-specific face processing mechanism. fMRI and MEG studies
      show that there are a variety of neural profiles in developmental prosopagnosia,
      which is consistent with behavioral studies demonstrating that it is a
      heterogeneous disorder.

PMID- 16563739
TI  - Neuroimaging of syntax and syntactic processing.
AB  - Recent results challenge and refine the prevailing view of the way language is
      represented in the human brain. Syntactic knowledge and processing mechanisms
      that implement syntax in use are mapped onto neural tissue in experiments that
      harness both syntactic concepts and imaging technologies to the study of brain
      mechanisms in healthy and impaired populations. In the emerging picture, syntax
      is neurologically segregated, and its component parts are housed in several
      distinct cerebral loci that extend beyond the traditional ones - Broca's and
      Wernicke's regions in the left hemisphere. In particular, the new brain map for
      syntax implicates portions of the right cerebral hemisphere.

PMID- 16563740
TI  - The mechanism of pore formation by bacterial toxins.
AB  - A remarkable group of proteins challenge the notions that protein sequence
      determines a unique three-dimensional structure, and that membrane and soluble
      proteins are very distinct. The pore-forming toxins typically transform from
      soluble, monomeric proteins to oligomers that form transmembrane channels. Recent
      structural studies provide ideas about how these changes take place. The recently
      solved structures of the beta-pore-forming toxins LukS, epsilon-toxin and
      intermedilysin confirm that the pore-forming regions are initially folded up on
      the surfaces of the soluble precursors. To create the transmembrane pores, these
      regions must extend and refold into membrane-inserted beta-barrels.

PMID- 16563741
TI  - Recent atomic models of amyloid fibril structure.
AB  - Despite the difficulties associated with determining atomic-level structures for
      materials that are fibrous, structural biologists are making headway in
      understanding the architecture of amyloid-like fibrils. It has long been
      recognized that these fibrils contain a cross-beta spine, with beta-strands
      perpendicular to the fibril axis. Recently, atomic structures have been
      determined for some of these cross-beta spines, revealing a pair of beta-sheets
      mated closely together by intermeshing sidechains in what has been termed a
      steric zipper. To explain the conversion of proteins from soluble to fibrous
      forms, several types of models have been proposed: refolding, natively disordered
      and gain of interaction. The gain-of-interaction models may additionally be
      subdivided into direct stacking, cross-beta spine, three-dimensional domain
      swapping and three-dimensional domain swapping with a cross-beta spine.

PMID- 16563743
TI  - Mass spectrometry of macromolecular assemblies: preservation and dissociation.
AB  - Mass spectrometry not only plays a crucial role in the identification of proteins
      involved in the intricate interaction networks of the cell, but also is
      increasingly involved in the characterization of the non-covalent complexes
      formed by interacting partners. Recent developments have enabled the use of gas
      phase dissociation to probe oligomeric organization and topology, and increased
      understanding of the electrospray process is leading to knowledge of the
      structure of protein assemblies both in solution and in the gas phase.

PMID- 16563742
TI  - Structure and function of myosin filaments.
AB  - Myosin filaments interact with actin to generate muscle contraction and many
      forms of cell motility. X-ray and electron microscopy (EM) studies have revealed
      the general organization of myosin molecules in relaxed filaments, but technical
      difficulties have prevented a detailed description. Recent studies using improved
      ultrastructural and image analysis techniques are overcoming these problems.
      Three-dimensional reconstructions using single-particle methods have provided
      many new insights into the organization of the myosin heads and tails. Docking of
      atomic structures into cryo-EM density maps suggests how regulated myosin
      filaments are 'switched off', bringing about muscle relaxation. Additionally,
      sequence analysis suggests probable interactions between myosin tails in the
      backbone, whereas crystallographic and EM studies are starting to reveal tail
      interactions directly in three dimensions.

PMID- 16563744
TI  - Budding invasive margin and prognosis in colorectal cancer--no direct association
      with beta-catenin expression.
AB  - Cancer cell budding at the invasive margin has been associated with poor
      prognosis in rectal cancer. beta-Catenin is an adhesion protein involved in the
      nuclear Wnt/beta-catenin pathway, and mesenchymal transition of colorectal cancer
      cells. Hence, we investigated the relationship between cancer cell budding at the
      invasive margin, beta-catenin expression, and 5-year-survival in colorectal
      cancer. Four hundred and sixty six colorectal cancer specimens were analysed for
      budding margin, and 108 specimens from the same set for beta-catenin by
      immunohistochemistry. A budding margin was present in 24.0% of the cases and
      predicted a poor 5-year-survival (15.4%, P < 0.00001). Nuclear beta-catenin
      expression increased from the central area towards the invasive margin (P <
      0.001), but did not predict budding. Budding margin is an independent factor
      associated with poor prognosis in colorectal cancer, and could be utilised in
      diagnostic pathology. Nuclear beta-catenin was often found at the invasive
      margin, but is unlikely to be the sole cause of budding.

PMID- 16563745
TI  - Impact of an information booklet on satisfaction and decision-making about BRCA
      genetic testing.
AB  - The aim of this study was to assess the impact of a standardized patient
      information booklet on decisions women make about genetic testing. This French
      national multi-centre survey included all women with cancer to whom genetic
      testing for BRCA1/2 mutation had been proposed. The control group was surveyed
      before the booklet became available (n = 263), and the experimental group, after
      being given it personally (n = 297). After multivariate adjustment, the booklet
      had a positive impact on satisfaction with the information provided (Odds ratio
      (OR) = 2.9; 99% confidence interval (CI) = 1.7-5.0; P = 0.001), decreased the
      decisional conflicts due to lack of information (OR = 1.9; 99% CI = 1.1-3.3; P =
      0.002), and had a marginal impact on knowledge (R2-gain = 3%; P = 0.001). The
      women in the experimental group decided more frequently to undergo testing (99%
      vs. 95%; P = 0.009). In addition to a consultation providing more tailored
      information, a standardized written document improved the decision-making process
      involved in giving informed consent to genetic testing.

PMID- 16563746
TI  - Kinetics of growth and ethanol production on different carbon substrates using
      genetically engineered xylose-fermenting yeast.
AB  - Saccharomyces cerevisiae 424A (LNH-ST) strain was used for fermentation of
      glucose and xylose. Growth kinetics and ethanol productivity were calculated for
      batch fermentation on media containing different combinations of glucose and
      xylose to give a final sugar concentration of 20+/-0.8 g/L. Growth rates obtained
      in pure xylose-based medium were less than those for media containing pure
      glucose and glucose-xylose mixtures. A maximum specific growth rate micro(max) of
      0.291 h(-1) was obtained in YPD medium containing 20 g/L glucose as compared to
      0.206 h(-1) in YPX medium containing 20 g/L xylose. In media containing
      combinations of glucose and xylose, glucose was exhausted first followed by
      xylose. Ethanol production on pure xylose entered log phase during the 12-24h
      period as compared to the 4-10h for pure glucose based medium using 2% inoculum.
      When glucose was added to fermentation flasks which had been initiated on a pure
      xylose-based medium, the rate of xylose usage was reduced indicating cosubstrate
      inhibition of xylose consumption by glucose.

PMID- 16563747
TI  - Aerobic degradation of diethyl phthalate by Sphingomonas sp.
AB  - An aerobic diethyl phthalate (DEP) degrading bacterium, DEP-AD1, was isolated
      from activated sludge. Based on its 16S rDNA sequence, this isolate was
      identified belonging to Sphingomonas genus with 99% similarity to Sphingomonas
      sp. strain C28242 and 98% similarity to S. capsulate. The specific degradation
      rate of DEP was concentration dependent with a maximum of 14 mg-DEP/(Lh). Results
      of degradation tests showed that DEP-AD1 could also degrade monoethyl phthalate
      (MEP), dimethyl phthalate (DMP), dibutyl phthalate (DBP), and diethylhexyl
      phthalate (DEHP), but not phthalate and benzoate.

PMID- 16563748
TI  - Effect of inclusion of tree leaves in feed on nutrient utilization and rumen
      fermentation in sheep.
AB  - The effect of inclusion of tree leaves in mustard (Brassica campestris) straw
      (MS) based complete feed blocks (CFB) on nutrient utilization and rumen
      fermentation was studied in adult male sheep. Four types of CFB diets
      (Roughage:Concentrate:Molasses, 70:25:5) were prepared. The compaction process
      increased bulk density (g/cm(3)) of MSB, MSNL, MSSL and MSAL by 2.9, 1.79, 2.40
      and 2.26 times, respectively. The dry matter intake (g/day) was higher (P<0.05)
      in MSSL and MSAL than in MSB. Digestibility coefficients of crude protein and
      hemicellulose increased (P<0.05) due to inclusion of tree leaves, while
      digestibility of dry matter and organic matter showed small improvement. However,
      inclusion of tree leaves did not affect digestibility of neutral detergent fibre,
      cellulose and energy. The concentration of total volatile fatty acids in rumen
      was significantly higher in MSAL than in MSB or MSSL. Blood bio-chemical
      parameters were within the normal physiological range in all the groups.

PMID- 16563749
TI  - Coconut water as a medium additive for the production of docosahexaenoic acid
      (C22:6 n3) by Schizochytrium mangrovei Sk-02.
AB  - The effect of coconut water (CW) on biomass and docosahexaenoic acid (DHA, C22:6
      n3) formation by Schizochytrium mangrovei Sk-02 was studied in a yeast extract
      diluted sea water medium. Optimal CW-level was ca. 33% (v/v), resulting in a
      biomass level of 28 g/l with a DHA-content of 20% (w/w) or 6 g DHA/l, almost 50%
      higher than in non-supplemented cultures at the same initial sugar level. Study
      on the growth-promoting effects of coconut water suggested that it could be
      (partially) mimicked by addition of trace elements; the fatty acids present in CW
      did not appear to be incorporated or effect fatty acid formation by the organism.
      CW-addition was also effective in media with other nitrogen sources such as
      casitone, peptone and tryptone. Its inclusion (at 50% v/v) increased biomass
      levels two-to-three-fold with concomitant increases in the DHA-level.

PMID- 16563750
TI  - Use of inexpensive nitrogen sources and starch for L(+) lactic acid production in
      anaerobic submerged fermentation.
AB  - L(+) Lactic acid fermentation was studied by Lactobacillus amylophilus GV6 under
      the influence of inexpensive nitrogen sources (red lentil-RL, and Baker's yeast
      cells-YC) and starch by response surface methodology (RSM). Central composite
      rotatable design (CCRD) was employed to determine maximum lactic acid production
      at optimum values for process variables RL, YC and incubation period (IP) and a
      satisfactory fit model was realized. Lactic acid production was significantly
      affected by RL and IP interactions as well as by independent variables RL and YC.
      Maximum lactic acid production of 13.5 g/15.2g starch was obtained with RL 0.8%,
      YC 1% and IP of 48 h, with 92% lactic acid yield efficiency (g lactic acid
      produced/g substrate utilized) and 40% increase (from 50 g to 92 g/100 g starch
      utilized) in lactic acid production. This is the first report on response
      optimization in direct fermentation of starch to lactic acid using inexpensive
      nitrogen sources substituting peptone and yeast extract in anaerobic submerged
      fermentation by amylolytic lactic acid bacteria (LAB).

PMID- 16563751
TI  - Two novel aromatic valerenane-type sesquiterpenes from the Chinese green alga
      Caulerpa taxifolia.
AB  - Caulerpal A (2) and B (3), two novel sesquiterpenes possessing an uncommon
      aromatic valerenane-type carbon skeleton, along with one known metabolite,
      caulerpin (4), have been isolated from the Chinese green alga Caulerpa taxifolia
      (Vahl) C. Agardh. Their structures and relative stereochemistry were elucidated
      on the basis of extensive spectroscopic analysis. Compounds 2-4 were evaluated
      for their inhibitory activity against hPTP1B and the result showed that only
      compound 4 had a strong PTP1B inhibitory activity with an IC50 value of 3.77
      microM.

PMID- 16563752
TI  - Discovery and initial SAR of inhibitors of interleukin-1 receptor-associated
      kinase-4.
AB  - High-throughput screening of a small-molecule compound library resulted in the
      identification of a novel series of N-acyl 2-aminobenzimidazoles that are potent
      inhibitors of interleukin-1 receptor-associated kinase-4.

PMID- 16563753
TI  - Further investigation of the N-demethylation of tertiary amine alkaloids using
      the non-classical Polonovski reaction.
AB  - The iron salt-mediated Polonovski reaction efficiently N-demethylates certain
      opiate alkaloids. In this process, the use of the hydrochloride salt of the
      tertiary N-methyl amine oxide was reported to give better yields of the desired N
      demethylated product. Herein, we report further investigation into the use of N
      oxide salts in the iron salt-mediated Polonovski reaction. An efficient approach
      for the removal of iron salts that greatly facilitates isolation and purification
      of the N-nor product is also described.

PMID- 16563754
TI  - Chemo-enzymatic synthesis of tetra-N-acetyl-chitotetraosyl allosamizoline.
AB  - A new compound 7, possessing a tetra-N-acetyl-chitotetraosyl moiety as a
      constituent, was synthesized by bacterial fermentation which used allosamizoline
      6 as the initial acceptor.

PMID- 16563755
TI  - Synthesis and evaluation of a mechanism-based inhibitor of a 3-deoxy-D-arabino
      heptulosonate 7-phosphate synthase.
AB  - The first mechanism-based inhibitor of a 3-deoxy-D-arabino heptulosonate 7
      phosphate (DAH7P) synthase has been synthesised in 12 steps from D-arabinose, and
      has been found to be a very slow binding inhibitor of Escherichia coli DAH7P
      synthase.

PMID- 16563756
TI  - Synthesis and preliminary antitumor activity evaluation of a DHA and doxorubicin
      conjugate.
AB  - A conjugate of DHA and doxorubicin (DHA-Dox) was synthesized, and its antitumor
      activity was evaluated in vitro against L1210 leukemia cells and in experimental
      animal tumor models including L1210 leukemia and B16 melanoma. DHA-Dox showed a
      greatly improved antitumor efficacy compared to free doxorubicin.

PMID- 16563757
TI  - Design, synthesis, and preliminary biological evaluation of 2,3-dihydro-3
      hydroxymethyl-1,4-benzoxazine derivatives.
AB  - We synthesized a series of novel small molecules, 2,3-dihydro-3-hydroxymethyl-1,4
      benzoxazine derivatives, by tandem reduction-oxirane opening of 2
      nitroaroxymethyloxiranes in moderate or excellent yields. We investigated the
      effects of all of the compounds on HUVEC apoptosis and A549 cell growth. The
      results showed that 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine was
      the most effective small molecule in promoting HUVEC apoptosis and inhibiting
      A549 cell proliferation, but 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine
      could remarkably inhibit HUVEC apoptosis and might induce the formation of
      microvessel.

PMID- 16563758
TI  - New potential biologically active compounds: design and an efficient synthesis of
      N-substituted 4-aryl-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-diones under
      microwave irradiation.
AB  - A series of N-substituted 4-aryl-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-diones
      were synthesized through a rapid one-pot four-component reaction under microwave
      irradiation. The method has the advantages of excellent yields (82-96%) and short
      reaction time (4-9 min). We provide new series of potential biologically active
      compounds for biomedical screening.

PMID- 16563759
TI  - A new non-azole inhibitor of ABA 8'-hydroxylase: effect of the hydroxyl group
      substituted for geminal methyl groups in the six-membered ring.
AB  - We designed and synthesized AHI4 that has an axial hydroxyl group instead of
      geminal methyl groups at C-6' of AHI1, previously reported as a lead compound for
      the development of non-azole inhibitors of ABA 8'-hydroxylase. (+)-AHI4
      competitively inhibited 8'-hydroxylation of ABA by recombinant CYP707A3. The K(I)
      value was found to be 0.14 microM, 10-fold less than that of (+)-AHI1, suggesting
      that enzyme affinity increased by a factor of 10 due to substitution of the
      hydroxyl group by the geminal methyls at C-6'. This finding should assist in the
      design of more effective, non-azole ABA 8'-hydroxylase inhibitors.

PMID- 16563760
TI  - The search for novel TRPV1-antagonists: from carboxamides to benzimidazoles and
      indazolones.
AB  - Based on a series of diaryl amides the corresponding inverse amides have been
      found to be potent TRPV1 receptor antagonists. Benzimidazole and indazolone
      derivatives prepared retained good potency in vitro and indazolone 4a was
      identified as a novel TRPV1 receptor antagonist suitable for evaluating orally in
      animal models of analgesia.

PMID- 16563761
TI  - Synthetic analogues of the manzamenones and plakoridines which inhibit DNA
      polymerase.
AB  - An array of novel analogues of the marine oxylipins, the manzamenones and
      plakoridines, have been prepared in divergent fashion using an approach modelled
      on a biogenetic theory. Many of the target compounds show potent inhibition of
      DNA polymerases alpha and beta and human terminal deoxynucleotidyl transferase
      (TdT).

PMID- 16563762
TI  - Polyamines and the NMDA receptor: modifying intrinsic activities with aromatic
      substituents.
AB  - Thirty-four spermidine (SPD) and spermine (SPM) derivatives with aromatic
      substituents were synthesized and tested as inhibitors of specific binding of the
      NMDA channel blocker [3H]MK-801 to membranes prepared from rat hippocampus and
      cerebral cortex. SPD and SPM derivatives with aromatic substituents at the
      primary amino groups were the most potent inhibitors (IC50 3.9-4.7 microM). These
      compounds most likely act directly at the NMDA ion channel, since 30 microM SPM
      had no pronounced influence on their inhibiting activities. SPD derivatives with
      aromatic substituents at the secondary amino group were either inactive or highly
      SPM-sensitive inhibitors (IC50 10-82 microM), depending on the size of the
      substituent. Our results support the hypothesis that an aromatic interaction site
      near the center of polyamine derivatives contributes to polyamine inverse
      agonism.

PMID- 16563763
TI  - Functional organisation and gain of activity: the case of the antibacterial tetra
      para-guanidinoethyl-calix[4]arene.
AB  - The antibacterial activities of the para-guanidinoethylphenol and of its cyclic
      tetramer, the tetra-para-guanidinoethyl-calix[4]arene, have been evaluated on
      reference gram-positive and gram-negative bacteria. Antibiotic disk diffusion
      assays completed by micromethod technique were employed to determine if a
      synergistic effect could be expected from the spatial organisation of the monomer
      into its cyclic tetrameric analogue. Disk diffusion assays and microdilution
      experiments revealed better properties for the calixarene species, with a real
      and important gain of activity with regards to the monomer.

PMID- 16563764
TI  - Synthesis and biological investigations of dopaminergic partial agonists
      preferentially recognizing the D4 receptor subtype.
AB  - Aminomethyl-substituted biaryls bearing a pyrazole or triazole moiety were
      synthesized and investigated for dopamine and serotonin receptor binding. The N
      arylpyrazoles 3b,f,g and 4 revealed Ki values in the subnanomolar range (0.28
      0.70 nM) for the dopamine D4 receptor subtype. Employing both mitogenesis and
      GTPgammaS assays, ligand efficacy was evaluated indicating partial agonist
      properties. Interestingly, the tetrahydropyrimidine 4 (FAUC 2020) displayed
      significant intrinsic selectivity for D2(long) over D2(short).

PMID- 16563765
TI  - UNC-6/netrin and SLT-1/slit guidance cues orient axon outgrowth mediated by MIG
      10/RIAM/lamellipodin.
AB  - BACKGROUND: Axon migrations are guided by extracellular cues that can act as
      repellants or attractants. However, the logic underlying the manner through which
      attractive and repulsive responses are determined is unclear. Many extracellular
      guidance cues, and the cellular components that mediate their signals, have been
      implicated in both types of responses. RESULTS: Genetic analyses indicate that
      MIG-10/RIAM/lamellipodin, a cytoplasmic adaptor protein, functions downstream of
      the attractive guidance cue UNC-6/netrin and the repulsive guidance cue SLT
      1/slit to direct the ventral migration of the AVM and PVM axons in C. elegans.
      Furthermore, overexpression of MIG-10 in the absence of UNC-6 and SLT-1 induces a
      multipolar phenotype with undirected outgrowths. Addition of either UNC-6 or SLT
      1 causes the neurons to become monopolar. Moreover, the ability of UNC-6 or SLT-1
      to direct the axon ventrally is enhanced by the MIG-10 overexpression. We also
      demonstrate that an interaction between MIG-10 and UNC-34, a protein that
      promotes actin-filament extension, is important in the response to guidance cues
      and that MIG-10 colocalizes with actin in cultured cells, where it can induce the
      formation of lamellipodia. CONCLUSIONS: We conclude that MIG-10 mediates the
      guidance of AVM and PVM axons in response to the extracellular UNC-6 and SLT-1
      guidance cues. The attractive and repulsive guidance cues orient MIG-10-dependant
      axon outgrowth to cause a directional response.

PMID- 16563766
TI  - Axial patterning and diversification in the cnidaria predate the Hox system.
AB  - Across the animal kingdom, Hox genes are organized in clusters whose genomic
      organization reflects their central roles in patterning along the
      anterior/posterior (A/P) axis . While a cluster of Hox genes was present in the
      bilaterian common ancestor, the origins of this system remain unclear (cf. ).
      With new data for two representatives of the closest extant phylum to the
      Bilateria, the sea anemone Nematostella and the hydromedusa Eleutheria, we argue
      here that the Cnidaria predate the evolution of the Hox system. Although Hox-like
      genes are present in a range of cnidarians, many of these are paralogs and in
      neither Nematostella nor Eleutheria is an equivalent of the Hox cluster present.
      With the exception of independently duplicated genes, the cnidarian genes are
      unlinked and in several cases are flanked by non-Hox genes. Furthermore, the
      cnidarian genes are expressed in patterns that are inconsistent with the Hox
      paradigm. We conclude that the Cnidaria/Bilateria split occurred before a
      definitive Hox system developed. The spectacular variety in morphological and
      developmental characteristics shown by extant cnidarians demonstrates that there
      is no obligate link between the Hox system and morphological diversity in the
      animal kingdom and that a canonical Hox system is not mandatory for axial
      patterning.

PMID- 16563767
TI  - The influence of patient complexity and nurses' experience on haemodynamic
      decision-making following cardiac surgery.
AB  - Critical care nurses' haemodynamic decision-making in the immediate postoperative
      cardiac surgical context is complex. To optimise patient outcomes, nurses of
      varying levels of experience are required to make complex decisions rapidly and
      accurately. In a dynamic clinical context such as critical care, the quality of
      such decision-making is likely to vary considerably. The aim of this study was to
      describe variability of nurses' haemodynamic decision-making in the 2-hour period
      after cardiac surgery as a function of interplay between decision complexity,
      nurses' levels of experience, and the support provided. A descriptive study based
      on naturalistic decision-making was used. Data were collected using continuous
      non-participant observation of clinical practice for a 2-hour period and follow
      up interview. Purposive sampling was used to recruit 38 nurses for inclusion in
      the study. The quality of nurses' decision-making was influenced by interplay
      between the complexity of patients' haemodynamic presentations, nurses' levels of
      cardiac surgical intensive care experience, and the form of decision support
      provided by nursing colleagues. Two factors specifically influenced decision
      making quality: nurses' utilisation of evidence for practice and the experience
      levels of both nurses and their colleagues. The findings have implications for
      staff resourcing decisions and postoperative patient management, and may be used
      to inform nurses' professional development and education.

PMID- 16563769
TI  - Accessible yet not accessed? A literature review exploring factors which may
      prevent patients taking over the counter analgesia prior to attending Accident
      and Emergency.
AB  - Over the counter (OTC) analgesics are products which are widely available and
      publicly accessible. Contemporary healthcare policy encourages patients to take
      greater control over their health care and recovery [Department of Health and
      Children 2001. Quality and Fairness - A Health System for You, Health Strategy.
      Dublin, Stationery Office.]. Over the counter medication offers injured patients
      a degree of control over their pain experience, preventing unnecessary pain on
      transit to an Accident and Emergency (A&E) department. In terms of availability,
      the range and variety of analgesics available is ever increasing, as more and
      more ingredients are downgraded from prescription only medicine (POM) to OTC
      status. However, despite the increase in the availability of OTC analgesia and an
      emphasis on patient empowerment, the majority of patients continue to present to
      A&E without taking any prior analgesia. In a study of 391 patients, 81% of
      patients took no analgesia prior to attending the A&E department [Emergency Nurse
      9 (2002) 36]. Pain, as Cooper [Cooper, A., 1994. Pain Assessment in accident and
      Emergency. Accident and Emergency Nursing 2(1) (1994) 103] has noted, prompts
      people to make a rational decision to attend the A&E department. This literature
      review explores possible explanations as to why patients do not take OTC
      analgesia as a first line step in pain management.

PMID- 16563770
TI  - A simple model to analyze the effectiveness of linear time normalization to
      reduce variability in human movement analysis.
AB  - In this paper we propose a simple model to predict the effect of linear time
      normalization to reduce variability in human movement analysis. This model is
      based on analysis of the correlation between timing variables and total movement
      duration. We obtain a simple expression to predict the variation coefficient (CV)
      of the normalized variable as a function of the CV of the original one, the CV of
      the total movement duration and the correlation between both variables. Depending
      on the correlation coefficient, R, very different results can be obtained after
      normalization. If R is positive and high, the linear normalization process
      effectively decreases variability. However, an increase of variability of the
      normalized variable can be expected if R decreases. This model explains why
      linear normalization does not always reduce variability. The model is applied to
      an example of sit-to-stand movement in order to show its effectiveness and to
      illustrate the close relationship between the correlation coefficient and the
      suitability of linear time-scale normalization.

PMID- 16563772
TI  - Antisense oligonucleotides: efficient synthesis of 2'-O-methoxyethyl
      phosphorothioate oligonucleotides using 4,5-dicyanoimidazole. Are these
      oligonucleotides comparable to those synthesized using 1H-tetrazole as coupling
      activator?
AB  - Multiple 2'-O-methoxyethyl modified phosphorothioate oligonucleotides of 18-20
      mer in length were synthesized at various scales using 4,5-dicyanoimidazole (DCI)
      as coupling activator. Extensive synthetic, analytical (using ion-pair LC-MS),
      and in vivo pharmacological, toxicological studies showed that oligonucleotides
      made with DCI and 1H-tetrazole are chemically and biologically equivalent. This
      extensive study will help the oligonucleotide therapeutic industry to move from
      using a potentially explosive activator (1H-tetrazole) to a safe activator (DCI).

PMID- 16563771
TI  - Spacer length and attaching position-dependent binding of synthesized
      protoberberine dimers to double-stranded DNA.
AB  - Six jatrorrhizine homodimers and berberine-jatrorrhizine heterodimers have been
      synthesized in moderate to good yields from the reaction of jatrorrhizine with
      alpha,omega-dibromoalkanes and 9-O-(omega-bromoalkyl)berberines, respectively.
      Their binding activities toward calf thymus (CT) DNA and three double-stranded
      oligodeoxynucleotides, d(AAGAATTCTT)(2), d(TAAGAATTCTTA)(2), and
      d(TTAAGAATTCTTAA)(2), were investigated by means of spectrofluorimetric and
      spectrophotometric titrations. The results indicate that these dimers exhibit
      enhanced DNA-binding affinities due to the cooperative interaction of the two
      protoberberine subunits. A comparative study of the DNA-binding behaviors of
      berberine homodimers, jatrorrhizine homodimers, and berberine-jatrorrhizine
      heterodimers suggests that spacer length and attaching position are of great
      importance in modulating their DNA-binding affinities.

PMID- 16563773
TI  - Studies on quinones. Part 41: synthesis and cytotoxicity of isoquinoline
      containing polycyclic quinones.
AB  - In the search for new potentially anticancer drugs, isoquinolinequinone
      containing polycyclic compounds have been designed and synthesized through highly
      regiocontrolled cycloaddition reactions of methyl 1,3-dimethyl-5,8-dioxo-5,8
      dihydroisoquinoline-4-carboxylate with polarized 1,3-dienes and a thiazole-o
      quinodimethane. The new N-heterocyclic quinones were tested on normal human
      fibroblasts and four distinct human cancer cell lines. Two of the evaluated
      compounds displayed significant in vitro activity (IC50: 0.44-5.9 microM)
      comparable to that of the reference drug etoposide.

PMID- 16563774
TI  - Transformations of bioactive peptides in the presence of sugars--characterization
      and stability studies of the adducts generated via the Maillard reaction.
AB  - Glycation of biomolecules, such as proteins, peptide hormones, nucleic acids, and
      lipids, may be a major contributor to the pathological manifestations of aging
      and diabetes mellitus. These nonenzymatic reactions, also termed the Maillard
      reaction, alter the biological and chemical properties of biomolecules. In order
      to investigate the effect of various reducing sugars on the products formed from
      small bioactive peptides (Tyr-Gly-Gly-Phe-Leu, Tyr-Gly-Gly-Phe-Leu-NH2, Tyr-Gly
      Gly-Phe-Leu-OMe, Tyr-Gly-Gly-Phe, and Tyr-Gly-Gly), model systems were prepared
      with glucose, mannose or galactose. Peptide-sugar mixtures were incubated at 37
      or 50 degrees C in phosphate-buffered saline, pH 7.4, or in methanol. The extent
      of glycation was determined periodically by RP HPLC. All sugar-peptide mixtures
      generated two different types of glycation products: N-(1-deoxy-ketos-1-yl)
      peptide (Amadori compound) and the imidazolidinone compound substituted by sugar
      pentitol and peptide residue. The amount and distribution of peptide glycation
      products depended on the structure of the reactants, and increased in both
      concentration- and time-dependent manner in relation to exposure to sugar.
      Additionally, the rate of hydrolysis of glucose-derived imidazolidinone
      compounds, obtained either from leucine-enkephalin (1) or its shorter N-terminal
      fragments 2 and 3, was determined by incubation at 37 degrees C in human serum.
      These results revealed that imidazolidinones obtained from glucose and small
      peptides are almost completely protected from the action of enzymes in serum, the
      predominant route of degradation being spontaneous hydrolysis to initial sugar
      and peptide compound.

PMID- 16563775
TI  - Structure-activity relationships of substituted N-benzyl piperidines in the GBR
      series: Synthesis of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2
      trifluoromethylbenzyl)piperidine, an allosteric modulator of the serotonin
      transporter.
AB  - A series of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-(substituted benzyl)
      piperidines with substituents at the ortho and meta positions in the aromatic
      ring of the N-benzyl side chain were synthesized and their affinities and
      selectivities for the dopamine transporter (DAT), serotonin transporter (SERT),
      and norepinephrine transporter (NET) were determined. One analogue, 4-(2-(bis(4
      fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piperidine (the C(2)
      trifluoromethyl substituted compound), has been found to act as an allosteric
      modulator of hSERT binding and function. It had little affinity for any of the
      transporters. Several compounds showed affinity for the DAT in the low nanomolar
      range and displayed a broad range of SERT/DAT selectivity ratios and very little
      affinity for the NET. The pharmacological tools provided by the availability of
      compounds with varying transporter affinity and selectivity could be used to
      obtain additional information about the properties a compound should have to act
      as a useful pharmacotherapeutic agent for cocaine addiction and help unravel the
      pharmacological mechanisms relevant to stimulant abuse.

PMID- 16563776
TI  - HREM of the [111] surfaces of iron oxide nanoparticles.
AB  - Mixed phase Fe3O4-gamma-Fe2O3 (magnetite-maghemite) iron oxide nanoparticles have
      been fabricated by colloidal routes. HRTEM/HRSTEM images of the nanoparticles
      show the presence of [111] facets that terminate with enhanced contrast, which is
      shown to be caused by the presence of additional cations at the edges of the
      nanoparticles. HRTEM images were taken on a FEI CM200 FEGTEM, a JEOL 3100 with a
      LaB6 source, and a double aberration corrected JEOL-JEM 2200FS FEGTEM. The
      enhanced contrast effect was observed on the [111] surface atomic layers resolved
      using each machine. HRSTEM images, taken on an aberration corrected STEM,
      resolved enhanced contrast at specific surface sites. Exit wave reconstruction
      was also carried out on focal series taken on a double aberration corrected JEOL
      JEM 2200FS and showed similar highly resolved enhanced contrast at specific
      surface cation sites. It is apparent that additional cations are occupying the
      [111] terminating layers of these nanoparticle surfaces. The use of different
      microscopes and techniques in this paper provides strong evidence that the
      enhanced contrast is a real effect and not an effect caused by microscope
      aberrations.

PMID- 16563777
TI  - Energy-loss near-edge fine structures of iron nanoparticles.
AB  - Body centered cubic (bcc) Fe nanoparticles were fabricated by in situ
      decomposition of iron fluoride films in a transmission electron microscope.
      Electron energy-loss near edge structure (ELNES) was used to characterize this
      exposure process. In particular, the L(3)/L(2) white-line intensity ratio (WLR)
      was used to monitor the iron valence state during exposure, and as an indicator
      of other properties of the iron nanoparticles. Iron nanoparticles with sizes
      between 2 and 20nm exhibit a constant WLR, whose value is same as that for a
      continuous bcc iron film, suggesting little or no dependence of the local
      magnetic moment or structure on the particle size. A broad but prominent peak
      which occurs 40eV after the L(3)-ionization threshold in the iron fluoride, is
      absent for a metallic iron film but reappears when the iron is converted to an
      oxide. Long-range ferromagnetic coupling was observed in samples densely
      populated with iron nanoparticles. Because there is little interaction between
      particles and the supporting carbon substrate, these samples provide an ideal
      model system for studying the influence of particle size and interparticle
      distance on magnetic properties.

PMID- 16563779
TI  - Standardization of tritiated water by two improved methods.
AB  - Tritiated water has been standardized in the framework of a French-Romanian
      cooperation by two improved methods: liquid scintillation counting based on the
      triple to double coincidence ratio method and the internal gas proportional
      counting used in conjunction with a tritium generator for chemical reduction of
      water. The uncertainties of measurement for both methods were smaller than 0.6%
      and the two results were consistent within these uncertainties, indicating that
      either method is equally suited for standardizing tritiated water.

PMID- 16563780
TI  - The LSC efficiency for low-Z electron-capture nuclides.
AB  - In this paper, we apply the CIEMAT/NIST method to the three low-Z electron
      capture nuclides 54Mn, 55Fe and 65Zn by using the KLM and KL1L2L3M atomic
      rearrangement models, respectively. The counting efficiencies are computed with
      the new code EMILIA, which comprises an improved model for the interaction of low
      energy X-rays with the scintillation cocktail. The calculated counting
      efficiencies are compared with experimental results.

PMID- 16563781
TI  - The IFIN-HH triple coincidence liquid scintillation counter.
AB  - The paper summarizes the IFIN-HH triple coincidence liquid scintillation counter
      used for the implementation of the TDCR method. The electronic unit was recently
      extended to record the three individual double coincidence ratios to take into
      account the differences in the quantum efficiencies of the three-photomultiplier
      tubes. Some details of the electronic system and the data processing are given.
      The critical point of a TDCR counter is to adjust correctly the discriminator
      levels on the three channels under the single electron peak. The paper describes
      the method of adjustment based on the evolution of the dark counting rate versus
      the discriminator level. Also indicated is the influence of the discrimination
      level on the activity results as measured at IFIN-HH using a 3H standard. The
      performances of the IFIN-HH TDCR counter was checked against the measurement
      results of the TDCR counters of CSIR NML (South Africa), RC (Poland) and LNHB
      (France). A set of ready-to-measure 63Ni sources in liquid scintillator, in
      sealed counting vials, was prepared and dispatched for measurement to all these
      laboratories. The paper describes designs of the TDCR counters used. An analysis
      and discussion of the measurement results is given.

PMID- 16563782
TI  - Assessing the 210At impurity in the production of 211At for radiotherapy by 210Po
      analysis via isotope dilution alpha spectrometry.
AB  - A method for assessing the impurity 210At in cyclotron-produced 211At via isotope
      dilution alpha spectrometry is presented. The activity of 210At is quantified by
      measuring the activity of daughter nuclide 210Po. Counting sources are prepared
      by spontaneous deposition of Po on a silver disc. Activity of 210At (at the time
      of 210Po maximum activity) is found to be 83.5+/-9.0 Bq, corresponding to an atom
      ratio (210At:211At at the time of distillation) of 0.010+/-0.007% (k=2). The
      method produces high-quality alpha spectra, with baseline alpha-peak resolution
      and chemical yields of greater than 85%.

PMID- 16563783
TI  - Oxidative stress in peripheral blood mononuclear cells from patients with
      Parkinson's disease: negative correlation with levodopa dosage.
AB  - Oxidative stress, resulting from the imbalance between reactive oxygen species
      (ROS) formation and antioxidant defenses, plays a major role in the pathogenesis
      of Parkinson's disease (PD). However, the contribution of levodopa (LD) therapy
      to oxidative damage is still debated. We investigated oxidative stress in
      peripheral blood mononuclear cells (PBMCs) from LD-treated PD patients and
      healthy subjects. Increased ROS production associated with unaltered glutathione
      reductase activity was detected in PBMC from PD patients. LD daily dosage
      appeared to be inversely correlated with ROS levels and positively associated
      with GR activity, suggesting a protective role for LD on PBMCs redox status. Our
      data support the view of systemic oxidative stress involvement in PD and give
      further rationale for using PBMCs as an easily accessible ex-vivo dopaminergic
      model for exploring the biological effects of LD therapy.

PMID- 16563784
TI  - Investigating myocardial motion by MRI using tissue phase mapping.
AB  - OBJECTIVE: Velocity-encoded phase contrast magnetic resonance imaging (MRI)
      provides a tool to quantify regional myocardial wall motion of the entire heart.
      It allows the acquisition of three-directional velocity vector fields with high
      spatial resolution that reflect the temporal evolution of myocardial velocities
      over the cardiac cycle. In contrast to other imaging modalities such as
      echocardiography left ventricular performance can be assessed without limited
      anatomical or functional coverage. METHODS: Compared to other techniques that
      quantify local myocardial contractility (e.g. implanted ultrasonic crystals) by
      means of regional displacement, phase contrast MRI provides information about
      local and global left ventricular velocities (i.e. motion) by utilizing the
      intrinsic motion sensitivity of MRI. The resultant motion components of
      contraction, expansion, rotation, lengthening, and shortening of the left
      ventricle are described in high spatial and temporal detail. Phase contrast
      measurements were performed in 12 healthy volunteers with a respiratory-gated
      technique in order to achieve a high temporal resolution of 13.8ms to demonstrate
      the detailed assessment of global and regional myocardial motion. RESULTS: Data
      revealed details in left ventricular motion patterns that were previously not
      seen in phase contrast measurements and are only known from echocardiography. For
      all volunteers, characteristic myocardial motion patterns and locally different
      radial (i.e. contraction and expansion), rotational (i.e. twisting and
      untwisting) and longitudinal (i.e. lengthening and shortening) motion components
      could be detected with high accuracy. CONCLUSIONS: The phase contrast MRI
      technique for high temporal resolution velocity mapping is therefore very
      promising for the investigation and better understanding of the myocardial motion
      in normal subjects and patients with disturbed left ventricular performance and
      may validate further testing of different models of cardiac structure.

PMID- 16563785
TI  - 'The electrical spiral of the heart': its role in the helical continuum. The
      hypothesis of the anisotropic conducting matrix.
AB  - The study of the dissemination of the electrical impulse throughout the
      ventricular myocardium, which gave rise to the current theories, was carried out
      without taking into consideration the complex architecture of the cardiac muscle
      elucidated by more recent researchers. We propose a novel hypothesis based on the
      special macroscopic structure of the heart, the anisotropic electrical and
      mechanical behavior of the myocardium, the characteristics of the intercellular
      matrix and its very special collagen scaffolding, chemical composition, and
      biochemistry. The unique properties of the intercellular matrix would make it
      especially suited to function, in conjunction with the specialized conducting
      system (His-Purkinje system) as an efficient anisotropic conductor for the spread
      of electrical activation in the heart in order to allow an optimal sequence of
      excitation-contraction coupling that results in the coordination of effective
      myocardial contraction in birds and mammals of the most varied known heart rates.
      An analysis of certain clinical conditions that raise questions regarding current
      hypothesis and a review of novel techniques for recording transmembrane and
      extracellular potentials, which will provide a much firmer basis for the study of
      cardiac activation and the influence of myofiber architecture and which will
      allow in depth testing of hypotheses are presented.

PMID- 16563786
TI  - The effect of ventricular sequential contraction on helical heart during pacing:
      high septal pacing versus biventricular pacing.
AB  - OBJECTIVE: To investigate the effect of biventricular and high septal pacing on
      the normal contraction sequence of the helical ventricular myocardial band, and
      its impact on left ventricular function. METHODS: Ten pigs (25-68 kg) underwent
      analysis of percent segmental shortening (SS%) by sonomicrometry, with crystals
      placed along the fiber orientation of the ascending, descending segments, and
      posterior LV wall within the spatial geometry of the helical heart. Unipolar
      pacing electrodes stimulated the right atrium (RA) and either the right
      ventricular apex and left ventricular posterior wall (atrio-biventricular), or
      the proximal high septum (atrio-high septal). Systemic hemodynamics, QRS
      interval, cardiac index (CI), systolic and diastolic LV functions and pressure
      dimension loops (P-D) were analyzed and cardiac motion was monitored by video
      analysis. RESULTS: Pacing increased normal sinus heart rate (NSR) from 77+/-9
      beats/min to 98+/-5 beats/min. Atrial pacing did not change the NSR hemodynamic
      variables. Conversely, atrio-biventricular pacing prolonged the QRS-interval
      (91+/-14 ms vs 56+/-11 ms at baseline, p<0.05) and decreased mean arterial
      pressure (50+/-4 mmHg vs 58+/-12 mmHg), CI (3.4+/-0.3 L/(min m2) vs 4.0+/-0.8
      L/(min m2)) and PRSW (71+/-25%) compared to NSR (p<0.05). Furthermore, atrio
      biventricular pacing decreased SS% in all segments, especially at the LV
      posterior wall (71% of baseline, p<0.05), and disrupted the NSR shortening
      sequence (progression from descending to posterior to ascending regions). Changes
      were characterized by premature stimulation of the posterior wall segment
      adjacent to the pacer stimulus, with associated (1) decrease of pressure
      dimension loop area, (2) desynchronization of P-D loops and (3) consistent loss
      of the twisting pattern of visible cardiac motion. In contrast, atrio-high septal
      pacing restored systemic hemodynamics, LV systolic and diastolic functions to
      baseline values and preserved the normal sequence of shortening of the
      ventricular myocardial band. CONCLUSIONS: (1) Biventricular pacing disrupts of
      the natural sequence of shortening of the myocardial band and results in impaired
      LV function. (2) High septal pacing preserves the sequential shortening pattern
      of the myocardial band and LV function.

PMID- 16563787
TI  - Cardiac motion and fiber shortening: the whole and its parts.
AB  - Radionuclide ventriculography findings in 24 subjects show that the ventricular
      blood pool motion goes from base to apex, a finding that contradicts the
      expectation that an apex to base relationship should exist, because excitation
      proceeds from apex to base. This discrepancy reflects a difference between motion
      caused by whole heart transmural action, and regional activity that does not
      require global movement. Confirmation of the radionuclide ventriculography
      findings was made from sonomicrometer crystals, echocardiography, and MRI that
      demonstrated early basal motion. During excitation, only the endocardial muscle
      is stimulated by the electrical impulse, but transmural motion that is needed for
      the endocardial motion that is detected by radionuclide ventriculography.
      Differences between the isometric and ejection phases are described, and there is
      discussion of how these findings relate to the myocardial band. The reality of
      twisting and downward motion of the heart observed during ejection only happens
      following transmural activation, a motion that exists far beyond the QRS
      electrical signal on the ECG.

PMID- 16563788
TI  - Morphological and functional evidences of the helical heart from non-invasive
      cardiac imaging.
AB  - The non-invasive study of cardiac mechanics has been improved after the recent
      introduction of advanced magnetic resonance and echocardiographic imaging
      techniques. Tagged and diffusion-sensitive cardiac magnetic resonance allows the
      study of myocardial torsion dynamics as well as the anatomical disposition of
      myocardial fibers. Local myocardial strain and synchronicity of myocardial
      contraction can also be determined with Doppler tissue imaging (DTI)
      echocardiography. Published results with these techniques demonstrate a
      mechanical behavior that is a consequence of a myocardial helical fiber
      orientation and strongly support the evidence of the double-loop single muscular
      band model described by Torrent-Guasp.

PMID- 16563789
TI  - Ontogenetic development of the helical heart: concepts and facts.
AB  - The structural and functional organization of the ventricular myocardial mass is
      a controversial matter that cannot be resolved by anatomical studies alone.
      Therefore, other approaches such as investigations of the ontogenetic development
      of the ventricular myocardium might help to resolve controversies about its
      structural and functional organization. It has recently been proposed that the
      spatial orientation of Torrent-Guasp's ventricular myocardial band model (basal
      and apical loops) might be the mature morphological correlate of twists and
      torsions of the embryonic heart loop. In the present contribution, the
      suggestions made in this concept were analyzed in the light of currently known
      facts about the development of the embryonic heart. It was found that some of the
      suggestions made in this concept do not correspond to embryological facts,
      whereas other suggestions could neither be disproved nor confirmed on the basis
      of our current knowledge on heart development. The answer to the question as to
      which of the various models of myocardial fibre organization fits best with the
      ontogenesis of the myocardial mass awaits future studies. The myocardial units of
      Torrent-Guasp's myocardial band model are said to have a functional rather than a
      morphological personality. Future studies on the ontogenetic development of the
      myocardium, therefore, should comprise not only anatomical analyses of dead
      specimens but should additionally comprise high resolution in vivo analyses of
      the development of the spatio-temporal contraction patterns of embryonic and
      fetal hearts.

PMID- 16563790
TI  - The helical ventricular myocardial band: global, three-dimensional, functional
      architecture of the ventricular myocardium.
AB  - We are currently witnessing the advent of new diagnostic tools and therapies for
      heart diseases, but, without serious scientific consensus on fundamental
      questions about normal and diseased heart structure and function. During the last
      decade, three successive, international, multidisciplinary symposia were
      organized in order to setup fundamental research principles, which would allow us
      to make a significant step forward in understanding heart structure and function.
      Helical ventricular myocardial band of Torrent-Guasp is the revolutionary new
      concept in understanding global, three-dimensional, functional architecture of
      the ventricular myocardium. This concept defines the principal, cumulative
      vectors, integrating the tissue architecture (i.e. form) and net forces developed
      (i.e. function) within the ventricular mass. Here we expose the compendium of
      Torrent-Guasp's half-century long functional anatomical investigations in the
      light of ongoing efforts to define the integrative approach, which would lead to
      new understanding of the ventricular form and function by linking across multiple
      scales of biological organization, as defined in ongoing Physiome project.
      Helical ventricular myocardial band of Torrent-Guasp may also, hopefully, allow
      overcoming some difficulties encountered in contemporary efforts to create a
      comprehensive mathematical model of the heart.

PMID- 16563791
TI  - Sequential deformation and physiological considerations in unipolar right or left
      ventricular pacing.
AB  - OBJECTIVE: To determine the effects of ventricular pacing on the normal
      contraction sequence of the helical ventricular myocardial band, and its' impact
      on left ventricular function. METHODS: Ten pigs (25-68 kg) underwent analysis of
      percent segmental shortening (%SS) by sonomicrometry, with crystals placed along
      the fiber orientation of the ascending and descending segments, and posterior LV
      wall of the geometry of the helical heart. Unipolar pacing electrodes stimulated
      either the right atrium (RA), right ventricular apex (RVA) and outflow tract
      (RVOT), or posterior LV wall. Systemic hemodynamics, QRS-interval, cardiac index
      (CI), systolic and diastolic LV function and pressure-dimension (P-D) loops were
      analyzed and cardiac motion was monitored by video analysis. RESULTS: Normal
      sinus heart rate (NSR) was elevated from 84+/-15 beats/min to 113+/-22 beats/min
      by pacing (p<0.05). The variables of NSR were not changed by atrial pacing.
      Conversely, compared with NSR, ventricular pacing (RVA, RVOT, LV) significantly
      (p<0.05) prolonged the QRS-interval (94-111 ms vs 52+/-7 ms, p<0.05) decreased
      mean arterial pressure (46-47 mmHg vs 62+/-11 mmHg), CI (2.7-3.4 L/(min m2) vs
      4.9+/-0.9L/(min m2)) and systolic LV pressure (56-61 mmHg vs 92+/-10 mmHg).
      Furthermore, ventricular pacing decreased peak +dP/dt and -dP/dt (p<0.05) and
      lowered PRSW to 59-77%, with most profound change after RVA pacing (p<0.05). Each
      ventricular pacing intervention decreased SS% significantly in the descending,
      ascending, and posterior LV segments compared with NSR. Disruption of the normal
      NSR sequence of shortening (progression from descending to posterior to ascending
      regions) followed each pacing intervention. Changes were characterized by
      premature stimulation of the segment adjacent to the pacer stimulus, with
      associated (1) decrease of pressure-dimension loop area, (2) desynchronization of
      P-D loops and (3) consistent loss of the twisting pattern of visible cardiac
      motion. CONCLUSIONS: Ventricular pacing disrupts the natural sequence of
      shortening along the myocardial band, and the resultant dyssynchrony impairs LV
      function.

PMID- 16563792
TI  - End-stage cardiomyopathy and secondary mitral insufficiency surgical alternative
      with prosthesis implant and left ventricular restoration.
AB  - BACKGROUND: Secondary mitral insufficiency is a strong risk factor for death in
      end-stage cardiomyopathy. The possible correction of mitral regurgitation has now
      been accepted as an alternative to cardiac transplantation in a special subset of
      patients. We propose a new surgical approach that consists of implantation of a
      mitral prosthesis that is smaller than the annulus, and preservation and traction
      of the papillary muscles to reduce sphericity of the left ventricle. METHODS:
      Between December 1995 and September 2005, 116 patients with dilated
      cardiomyopathy underwent this procedure, with the following etiologic factors:
      ischemic (68), idiopathic (43), Chagas disease (3), viral (1), and postpartum
      (1). The patients were analyzed according to clinical criteria, echocardiographic
      findings, and morphology of left ventricle. RESULTS: All patients were in an end
      stage phase, requiring >2 hospital admissions over the past 3 months, despite
      receiving full medication. Furthermore, seven were in intensive care unit
      receiving intravenous drugs or intra-aortic balloon counterpulsation, and one was
      in cardiogenic shock. Hospital mortality was 16.3% (19/116), yet midterm follow
      up showed a relatively flat late survival curve, with evidence of improved
      clinical status, better echocardiographic parameters, and reduction in
      ventricular sphericity. CONCLUSIONS: The high early mortality rate related to
      other clinical conditions at the time of surgery. However, the resultant flat
      survival after this early interval offers a promising long-term therapeutic
      alternative for the treatment of patients in refractory heart failure with
      cardiomyopathy that is associated with moderate or severe secondary mitral
      regurgitation.

PMID- 16563793
TI  - Left ventricular muscle band (VMB): thoughts on its physiologic and clinical
      implications.
AB  - Although the ventricular muscle band (VMB) is formed by one continuous band of
      myocardium and there is some evidence to suggest that it may contract
      sequentially along its course from the right ventricle, through the septum, then
      along its basoapical left ventricular spiral, the structure is not activated in
      this sequence. Activation as programmed by the fully developed Purkinje system
      proceeds broadly and directly from endocardium to epicardium and from apex to
      base. Although not activated sequentially along its course, the band may still
      contract and relax sequentially if there is a progressive lengthening of the
      contraction duration in association with a nonuniform lengthening of the cardiac
      fiber action potential (repolarization) duration. Also, the systolic and
      diastolic functions of the band should be considered as part of a complex,
      integrated electromechanical system in which the activation is programmed to
      ensure optimal function.

PMID- 16563794
TI  - Singlet oxygen quenching by thione analogues of canthaxanthin, echinenone and
      rhodoxanthin.
AB  - Thione analogues of three naturally occurring carotenones (canthaxanthin,
      echinenone, and rhodoxanthin) were synthesized just over ten years ago, and it
      was reported that substitution of the oxygen atom by sulphur brings about a large
      red shift and some broadening in the optical absorption spectrum of the compound.
      Since the three carotenothiones are scarce, determination of their molar
      absorption coefficients presents a challenge. A method for relating the molar
      absorption coefficient of a carotenothione (Car-S) to that of its ketone analogue
      (Car-O) has been developed, which has revealed that the peak molar absorption
      coefficient of a Car-S is only about 60% of the corresponding value for Car-O.
      Using methylene blue as the sensitizer and acetonitrile as the solvent, we have
      also investigated the quenching (under photostationary conditions) of the 1270nm
      phosphorescence emission of singlet oxygen by each of the six carotenoids. The
      data conform to the Stern-Volmer relation, and show that substitution of a
      carbonyl oxygen atom by sulphur does not lead to an appreciable change in the
      value of the quenching constant, which is close to 1.5 x 10(10)M(-1)s(-1) for all
      six quenchers.

PMID- 16563795
TI  - The induction of immunity to a protein antigen using an adjuvant is significantly
      compromised by ultraviolet A radiation.
AB  - Ultraviolet (UV) radiation from sunlight causes skin cancer and inhibits priming
      of the immune system during vaccination. However the dose related effects of the
      different components of sunlight (UVA and UVB) are complex and require further
      investigation. Using ovalbumin as a model protein vaccine with saponin as
      adjuvant we show that both UVA and UVB can suppress the DTH response to a poorly
      immunogenic protein. Increasing doses of UVB induced increased levels of
      immunosuppression and tolerance. UVA however, caused a bi-phasic dose response
      with intermediate but not low or high doses causing primary immunosuppression. No
      dose of UVA caused significant tolerance. Similar results were observed in both
      C57BL/6 and Balb/c mice. Our data confirms the complex immunomodulatory dose
      effects of UVA and UVB for a protein antigen, and shows that both UVB and UVA can
      suppress immunity induced by a protein with adjuvant. This highlights the
      importance of considering sun exposure patterns in the future success of both
      preventing skin cancer development and enhancing vaccination regimes.

PMID- 16563796
TI  - Directed evolution for improved secretion of cancer-testis antigen NY-ESO-1 from
      yeast.
AB  - NY-ESO-1 is a highly immunogenic tumor antigen and a promising vaccine candidate
      in cancer immunotherapy. Access to purified protein both for vaccine formulations
      and for monitoring antigen-specific immune responses is vital to vaccine
      development. Currently available recombinant Escherichia coli-derived NY-ESO-1 is
      isolated from inclusion bodies as a complex protein mixture and efforts to
      improve the purity of this antigen are required, especially for later-stage
      clinical trials. Using yeast cell surface display and fluorescence activated cell
      sorting techniques, we have engineered an NY-ESO-1 variant (NY-ESO-L5; C(75)A
      C(76)A C(78)A L(153)H) with a 100x improved display level on yeast compared to
      the wild-type protein. This mutant can be effectively produced as an Aga2p-fusion
      and purified in soluble form directly from the yeast cell wall. In the process,
      we have identified the epitope recognized by anti-NY-ESO-1 mAb E978 (79-87,
      GARGPESRL). The availability of an alternative expression host for this important
      antigen will help avoid artifactual false positive tests of patient immune
      response due to reaction against expression-host-specific contaminants.

PMID- 16563797
TI  - Flavodoxin, a new fluorescent substrate for monitoring proteolytic activity of
      FtsH lacking a robust unfolding activity.
AB  - Escherichia coli FtsH, which belongs to the ATPases associated with diverse
      cellular activities (AAA) family, is an ATP-dependent and membrane-bound
      protease. FtsH degrades misassembled membrane proteins and a subset of
      cytoplasmic regulatory proteins. To elucidate the molecular mechanisms of the
      proteolysis, a system for precisely monitoring substrate degradation is required.
      We have exploited E. coli flavodoxin containing non-covalently bound flavin
      mononucleotide (FMN) as a model substrate for monitoring protein degradation. It
      was found that FtsH degrades FMN-free apo-flavodoxin but not holo-flavodoxin.
      However, degradation of a mutant flavodoxin carrying a substitution of Tyr94 to
      Asp with a lower affinity for FMN could be monitored by fluorimetry. This newly
      developed monitoring system will also be applicable for proteolysis by other ATP
      dependent proteases.

PMID- 16563798
TI  - The molecular chaperone Hsp104--a molecular machine for protein disaggregation.
AB  - At the Cold Spring Harbor Meeting on 'Molecular Chaperones and the Heat Shock
      Response' in May 1996, Susan Lindquist presented evidence that a chaperone of
      yeast termed Hsp104, which her group had been investigating for several years, is
      able to dissolve protein aggregates (Glover, J.R., Lindquist, S., 1998. Hsp104,
      Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated
      proteins. Cell 94, 73-82). Among many of the participants this news stimulated
      reactions reaching from decided skepticism to utter disbelief because protein
      aggregation was widely considered to be an irreversible process. Several years
      and publications later, it is undeniable that Susan had been right. Hsp104 is an
      ATP dependent molecular machine that-in cooperation with Hsp70 and Hsp40-extracts
      polypeptide chains from protein aggregates and facilitates their refolding,
      although the molecular details of this process are still poorly understood.
      Meanwhile, close homologues of Hsp104 have been identified in bacteria (ClpB), in
      mitochondria (Hsp78), and in the cytosol of plants (Hsp101), but intriguingly not
      in the cytosol of animal cells (Mosser, D.D., Ho, S., Glover, J.R., 2004.
      Saccharomyces cerevisiae Hsp104 enhances the chaperone capacity of human cells
      and inhibits heat stress-induced proapoptotic signaling. Biochemistry 43, 8107
      8115). Observations that Hsp104 plays an essential role in the maintenance of
      yeast prions (see review by James Shorter in this issue) have attracted even more
      attention to the molecular mechanism of this ATP dependent chaperone (Chernoff,
      Y.O., Lindquist, S.L., Ono, B., Inge-Vechtomov, S.G., Liebman, S.W., 1995. Role
      of the chaperone protein Hsp104 in propagation of the yeast prion-like factor
      [PSI+]. Science 268, 880-884).

PMID- 16563799
TI  - Characterization of mutants of the Escherichia coli AAA protease, FtsH, carrying
      a mutation in the central pore region.
AB  - Escherichia coli FtsH is an ATP-dependent and membrane-bound protease, which
      belongs to the ATPases associated with diverse cellular activities family. FtsH
      degrades a subset of cytoplasmic regulatory proteins and misassembled membrane
      proteins. It has been proposed that ATP-dependent proteases unfold and
      translocate substrate proteins into the protease chamber. Previously, we reported
      that Phe228 and Gly230 in the conserved motif, @XG (where @ is an aromatic
      residue and X is any residue), in the central pore of the FtsH ATPase ring have
      important roles in proteolysis and its coupling to ATP hydrolysis. In this paper,
      we constructed and characterized additional pore mutants. Results indicated that
      certain acidic residues located in the pore region are also important for the
      activity of FtsH. Proteolytic activities of most mutants are correlated with
      their ATPase activities. Evidence also indicated that Val229, the 2nd residue of
      the @XG motif, may have a substrate-specific role.

PMID- 16563800
TI  - The influence of circadian rhythm on muscle activity and efficient force
      production during cycling at different pedal rates.
AB  - The aim of this study was to examine the pedal rate and chronobiological impacts
      on muscle activity pattern and propulsive force production during cycling. Ten
      male competitive cyclists performed at 06:00 and 18:00 h a submaximal exercise on
      a cycle ergometer at a power output which elicited 50% of their respective
      W(max). The exercise was divided into 4 periods lasting 5 min each during which
      subjects were requested to use different pedal rates (free pedal rate, 70, 90 and
      120 rev min-1) in random order. The study demonstrated that, under high pedal
      rate, several muscles exhibited a phase advance of activity. These modifications
      of temporal organization of muscle activity were not sufficient to keep an
      identical propulsive torque pattern. Time to peak torque was delayed when pedal
      rate increased. The effects of circadian fluctuation on electromyographic
      activity were limited to a later M. rectus femoris burst end and shorter activity
      duration for M. tibialis anterior at 06:00 h. From the results of this study, it
      seems that the influence of pedal rate in the range of torque fluctuation would
      depend on time-of-day of testing. The decrease in torque fluctuation due to pedal
      rate increase is reinforced when testing in the early morning. Taking this
      specific variable into consideration, the chronobiological effect increases the
      impact of pedal rate variations.

PMID- 16563801
TI  - Postural adaptations specific to preferred throwing techniques practiced by
      competition-level judoists.
AB  - The purpose of this study was to analyse the judoists' postural regulation
      adopted to accommodate their favorite throwing technique (tokui-waza). The tokui
      waza is a technique performed in bipodal or monopodal stance. Twenty three
      judoists aged between 16 and 20 took part in the protocol. All had a minimum
      regional sportive level. They were separated into two groups: the one performed a
      tokui-waza in bipodal stance (BS group) and the others performed a tokui-waza in
      monopodal stance (MS group). The medio/lateral and antero/posterior dynamic
      balance was evaluated on one-leg and two-leg support with a seesaw platform laid
      on a force platform. On two-leg support, the BS group judoists were more
      efficient than the MS group judoists. On the contrary, on one-leg support, the MS
      group was more efficient than the BS group. The different movements practiced on
      one or two-leg induce specific postural adaptations in competition-level
      judoists. Therefore, the present study shows that the different movements
      practiced in a given sport can induce particular postural adaptations. This
      phenomenon must therefore also be taken into account in the protocols used for
      evaluating postural control in sportsmen.

PMID- 16563802
TI  - Age-related degeneration of corpus callosum measured with diffusion tensor
      imaging.
AB  - The corpus callosum is the major commissure connecting the cerebral hemispheres,
      and there is evidence of its change with aging. The sub-regions of the corpus
      callosum (genu, rostral body, anterior midbody, posterior midbody, isthmus,
      splenium) respectively comprise fibers connecting heteromodal- and unimodal
      associated cortical regions, and it is known that abnormalities of the corpus
      callosum are correlated with abnormalities in cognition and behavior. Yet, little
      is known about changes in the tissue characteristics of its sub-regions. We
      assessed age-related changes in fractional anisotropy and mean diffusivity in the
      sub-regions of the corpus callosum using diffusion tensor imaging. We studied 42
      healthy right-handed individuals aged 21-73 years. There were no significant
      interactions of sex x region. Age has significant negative correlation with
      fractional anisotropy in the genu (P < 0.001), rostral body (P < 0.001), and
      isthmus (P = 0.005). Fractional anisotropy of the anterior midbody was correlated
      negatively with age at a trend level (P = 0.022). Age was significantly
      positively correlated with mean diffusivity in the genu (P = 0.001), rostral body
      (P = 0.002), anterior midbody (P = 0.001), and isthmus (P = 0.001). Age-related
      changes were detected in the sub-regions where their projection areas are thought
      to be vulnerable to normal aging. This suggested that fractional anisotropy and
      mean diffusivity values of the corpus callosum sub-regions could serve as markers
      of disturbance across the respective projection areas.

PMID- 16563803
TI  - Differential hippocampal and prefrontal-striatal contributions to instance-based
      and rule-based learning.
AB  - It is a topic of current interest whether learning in humans relies on the
      acquisition of abstract rule knowledge (rule-based learning) or whether it
      depends on superficial item-specific information (instance-based learning). Here,
      we identified brain regions that mediate either of the two learning mechanisms by
      combining fMRI with an experimental protocol shown to be able to dissociate both
      learning mechanisms. Subjects had to learn object-position conjunctions in
      several trials and blocks. In a learning condition, either objects (Experiment 1)
      or positions (Experiment 2) were held constant within-blocks. In contrast to a
      control condition in which object-position conjunctions were trial-unique, a
      performance increase within and across-blocks was observed in the learning
      condition of both experiments. We hypothesized that within-block learning mainly
      relies on instance-based processes, whereas across-block learning might depend on
      rule-based mechanisms. A within-block parametric fMRI analysis revealed a
      learning-related increase of lateral prefrontal and striatal activity and a
      learning-related decrease of hippocampal activity in both experiments. By
      contrast, across-block learning was associated with an activation modulation in
      distinct prefrontal-striatal brain regions, but not in the hippocampus. These
      data indicate that hippocampal and prefrontal-striatal brain regions
      differentially contribute to instance-based and rule-based learning.

PMID- 16563804
TI  - Improved fiber tractography with Bayesian tensor regularization.
AB  - Diffusion tensor tractography suffers from the effects of noise and partial
      volume averaging (PVA). For reliable reconstruction of fiber pathways, tracking
      algorithms that are robust to these artifacts are called for. To meet this need,
      the present study establishes a novel Bayesian regularization framework for fiber
      tracking that takes into account the effects of noise and PVA, thereby improving
      tracking accuracy and precision. With this framework, the propagation of a fiber
      path follows an optimal vector determined by Bayes decision rule; the probability
      functions involved are modeled on the basis of multivariate normal distributions
      of diffusion tensor elements, which allows the optimal solution with maximum a
      posteriori probability to be derived analytically. Parameters for the probability
      functions are estimated from the uncertainty of tensor elements and the variance
      among tensors within an oriented sampling volume weighted by fractional
      anisotropy. Experiments with Monte Carlo simulations, synthetic, and in vivo
      human diffusion tensor data demonstrate that this specialized scheme enhances the
      immunity of fiber tracking to noise and PVA, and hence enables fibers to be more
      faithfully reconstructed.

PMID- 16563805
TI  - Higher level phylogeny of Satyrinae butterflies (Lepidoptera: Nymphalidae) based
      on DNA sequence data.
AB  - We have inferred the first empirically supported hypothesis of relationships for
      the cosmopolitan butterfly subfamily Satyrinae. We used 3090 base pairs of DNA
      from the mitochondrial gene COI and the nuclear genes EF-1alpha and wingless for
      165 Satyrinae taxa representing 4 tribes and 15 subtribes, and 26 outgroups, in
      order to test the monophyly of the subfamily and elucidate phylogenetic
      relationships of its major lineages. In a combined analysis, the three gene
      regions supported an almost fully resolved topology, which recovered Satyrinae as
      polyphyletic, and revealed that the current classification of suprageneric taxa
      within the subfamily is comprised almost completely of unnatural assemblages. The
      most noteworthy findings are that Manataria is closely related to Melanitini;
      Palaeonympha belongs to Euptychiina; Oressinoma, Orsotriaena and Coenonympha
      group with the Hypocystina; Miller's (1968). Parargina is polyphyletic and its
      components group with multiple distantly related lineages; and the subtribes
      Elymniina and Zetherina fall outside the Satyrinae. The three gene regions used
      in a combined analysis prove to be very effective in resolving relationships of
      Satyrinae at the subtribal and tribal levels. Further sampling of the taxa
      closely related to Satyrinae, as well as more extensive sampling of genera within
      the tribes and subtribes for this group will be critical to test the monophyly of
      the subfamily and establish a stronger basis for future biogeographical and
      evolutionary studies.

PMID- 16563806
TI  - Optimisation and validation of a medium-throughput electrophysiology-based hERG
      assay using IonWorks HT.
AB  - INTRODUCTION: Regulatory and competitive pressure to reduce the QT interval
      prolongation risk of potential new drugs has led to focus on methods to test for
      inhibition of the human ether-a-go-go-related gene (hERG)-encoded K+ channel, the
      primary molecular target underlying this safety issue. Here we describe the
      validation of a method that combines medium-throughput with direct assessment of
      channel function. METHODS: The electrophysiological and pharmacological
      properties of hERG were compared using two methods: conventional, low-throughput
      electrophysiology and planar-array-based, medium-throughput electrophysiology
      (IonWorks HT). A pharmacological comparison was also made between IonWorks HT and
      an indirect assay (Rb+ efflux). RESULTS: Basic electrophysiological properties of
      hERG were similar whether recorded conventionally (HEK cells) or using IonWorks
      HT (CHO cells): for example, tail current V1/2 -12.1+/-5.0 mV (32) for
      conventional and -9.5+/-6.0 mV (46) for IonWorks HT (mean+/-S.D. (n)). A key
      finding was that as the number of cells per well was increased in IonWorks HT,
      the potency reported for a given compound decreased. Using the lowest possible
      cell concentration (250,000 cells/ml) and 89 compounds spanning a broad potency
      range, the pIC50 values from IonWorks HT (CHO-hERG) were found to correlate well
      with those obtained using conventional methodology (HEK-hERG)(r=0.90; p<0.001).
      Further validation using CHO-hERG cells with both methods confirmed the
      correlation (r=0.94; p<0.001). In contrast, a comparison of IonWorks HT and Rb+
      efflux data with 649 compounds using CHO-hERG cells showed that the indirect
      assay consistently reported compounds as being, on average, 6-fold less potent,
      though the differences varied depending on chemical series. DISCUSSION: The main
      finding of this work is that providing a relatively low cell concentration is
      used in IonWorks HT, the potency information generated correlates well with that
      determined using conventional electrophysiology. The effect on potency of
      increasing cell concentration may relate to a reduced free concentration of test
      compound owing to partitioning into cell membranes. In summary, the IonWorks HT
      hERG assay can generate pIC50 values based on a direct assessment of channel
      function in a timeframe short enough to influence chemical design.

PMID- 16563807
TI  - Cognitive problems related to epilepsy syndromes, especially malignant
      epilepsies.
AB  - Neurocognitive impairment is frequent in epilepsy patients. Causes are multiple,
      and may be influenced by several factors including the epilepsy syndrome. Most
      cognitive complaints in adult patients are mental slowness, memory difficulties
      and attention deficits. In children, cognitive problems are more diffuse,
      responsible for language troubles, learning difficulties, poor academic outcome,
      behavior problems and finally unfortunate socio-professional prognosis. The most
      devastating epilepsy syndromes such as epileptic encephalopathies are nearly
      exclusively described in infancy and childhood. This paper will review the major
      cognitive complaints in relation to the epilepsy syndrome, with a more detailed
      interest for the malignant epilepsies in infancy and childhood such as Ohtahara
      and West syndrome, Lennox-Gastaut syndrome and epileptic encephalopathis with
      continuous spike-and-wase during slow wave sleep. The impact of surgery on
      cognition will be briefly discussed in adults and youger patients.

PMID- 16563808
TI  - Cognitive side effects of anti-epileptic drugs. The relevance in childhood
      epilepsy.
AB  - In recent years several new anti-epileptic drugs have been introduced, also for
      the treatment of childhood epilepsy. A major concern is their effect on learning
      and cognitive development. Testing the genuine effects on cognition of the anti
      epileptic drugs is methodologically not easy. At this moment there are very few
      controlled trials that systematically examine the cognitive side effects of anti
      epileptic drugs in childhood epilepsy. The available data indicate that the newer
      anti-epileptic drugs have a safe cognitive profile when prescribed correctly at
      the right dose and in monotherapy. Possible negative effects are mainly found for
      speed of processing and attention processes. As these processes are important
      instruments in every day learning and cognition, it is necessary to test these
      newer anti-epileptic drugs in well designed studies and in specific childhood
      epilepsy syndromes.

PMID- 16563809
TI  - Cognitive rehabilitation of memory problems in patients with epilepsy.
AB  - People with epilepsy often complain about their memory. Memory deficits are also
      most commonly observed during neuropsychological evaluation. Many patients with
      memory problems ask for some kind of memory training. General memory improvement
      is not possible, but learning mnemonics clearly will help to solve some of the
      most common everyday memory problems of patients. Most mnemonics follow the
      general rules for good learning or memory. In the design of a memory
      rehabilitation program some specific aspect should be taken into account, such as
      the need for psycho-education into the effects of cognitive deficits in daily
      life, the impact of personality and emotional reactions, and the individual
      perception of memory problems. Training goals must be tailor-made, small and as
      concrete as possible and fully adjusted to the needs and wishes of the patients.
      Generalization of the learned mnemonics is mostly modest or even absent.

PMID- 16563810
TI  - Brace treatment for osteoarthritis of the knee: a prospective randomized multi
      centre trial.
AB  - OBJECTIVE: To evaluate the effect of a brace intended to reduce load in patients
      with medial or lateral compartmental osteoarthritis (OA) and concurrent varus or
      valgus alignment, respectively. DESIGN: This multi-centre randomized controlled
      trial (performed 2001-2003) studies the additive effect of a brace intended to
      reduce load in conservative treatment of unicompartmental OA of the knee.
      SETTING: Orthopedic department of a university medical centre and of one general
      hospital. The follow-up was 12 months. PATIENTS: 117 patients with
      unicompartmental OA of the knee. Intervention group (n=60) comprising
      conservative treatment with additional brace treatment and a control group (n=57)
      comprising conservative treatment alone. PRIMARY OUTCOME MEASURES: Pain severity
      and knee function score. SECONDARY OUTCOME MEASURES: Walking distance and quality
      of life. ANALYSIS: Multiple linear regression models according to the intention
      to-treat-principle were used to assess outcome differences for the entire group
      of patients. In addition, we performed explorative subgroup analyses on primary
      overall outcomes stratified for alignment, degree of OA, origin of OA, and age.
      RESULTS: Although the primary outcome measures were improved in the intervention
      group in comparison with the controls at each assessment point, the differences
      reached only borderline significance. The reported walking distances at 3 months,
      12 months and overall were significantly longer in the brace group (P=0.03,
      P=0.04 and P=0.02, respectively). Subgroup analysis showed a better effect in the
      varus group, in patients with severe OA, in patients with secondary OA and in
      patients younger then 60 years. In total 25 patients in the brace group and 14 in
      the control group changed their initial treatment, mostly (74%) because of a lack
      of beneficial effect. CONCLUSIONS: The results indicate that a brace intended to
      reduce load shows small effects in patients with unicompartmental OA. However,
      many patients do not adhere in the long run to this kind of conservative
      treatment.

PMID- 16563811
TI  - Relative contribution of matrix metalloprotease and cysteine protease activities
      to cytokine-stimulated articular cartilage degradation.
AB  - OBJECTIVE: Both matrix metalloprotease (MMP) activity and cathepsin K (CK)
      activity have been implicated in cartilage turnover. We investigated the relative
      contribution of MMP activity and CK activity in cartilage degradation using ex
      vivo and in vivo models. METHODS: Bovine articular cartilage explants were
      stimulated with oncostatin M (OSM) 10 ng/ml and tumor necrosis factor-alpha (TNF
      alpha) 20 ng/ml in the presence or absence of the broad-spectrum MMP inhibitor
      GM6001 and the cysteine protease inhibitor, E64. Cartilage degradation was
      evaluated in the conditioned medium by glycosaminoglycans (GAG), hydroxyproline,
      and cross-linked C-telopeptide fragments of type II collagen (CTX-II), which were
      compared to immunohistochemical evaluations of proteoglycans and CTX-II. We
      assessed MMP expression by gelatine zymography and CK expression by
      immunohistochemistry. In vivo, CTX-II release was measured from CK-deficient
      mice. RESULTS: OSM and TNF-alpha combined induced significant (P<0.01) increase
      in cartilage degradation products measured by hydroxyproline and CTX-II compared
      to vehicle control. The cytokines potently induced MMP expression, assessed by
      zymography, and CK expression investigated by immunohistochemistry. Inhibition of
      MMP activity completely abrogated hydroxyproline and CTX-II release (P<0.01) and
      GAG release (P<0.05). In contrast, E64 resulted in increased CTX-II release by
      100% (P<0.05) and inhibited GAG release by 30%. Up-regulation of CTX-II fragments
      was confirmed in vivo in CK null mice. CONCLUSION: Inhibition of MMP activity
      reduced both proteoglycan loss and type II collagen degradation. In contrast,
      inhibition of cysteine proteases resulted in an increase rather than a decrease
      in MMP derived fragments of collagen type II degradation, CTX-II, suggesting
      altered collagen metabolism.

PMID- 16563812
TI  - Maturation-dependent change and regional variations in acoustic stiffness of
      rabbit articular cartilage: an examination of the superficial collagen-rich zone
      of cartilage.
AB  - OBJECTIVE: The purpose of the study was to investigate maturation-dependent
      changes of acoustic (ultrasound) stiffness and other ultrasound features of
      articular cartilage in healthy rabbit knees. METHODS: Five groups of rabbits of
      various ages (3 weeks, 8 weeks, 6 months, 1 year, 2.5 years) consisting of five
      rabbits per group were examined. Signal intensity (index of stiffness), signal
      duration (index of surface irregularity) and interval between signals (index of
      thickness) of the ultrasound reflection from articular cartilage were examined at
      four sites: posterior lateral femoral condyle, posterior medial femoral condyle,
      lateral tibial plateau, and medial tibial plateau. The sites were observed
      macroscopically and microscopically with a light microscope and a polarized light
      microscope. RESULTS: At the lateral and medial condyles and the lateral tibial
      plateau, signal intensity was least in 3-week-old specimens. The intensity
      increased until 6 months or 1 year of age. At these sites, the signal durations
      and intervals between signals were least at the ages of 6 months or 1 year. At
      the medial tibial plateau, the intensity was the least at 2.5 years of age and
      the interval between signals was least at 3 weeks of age; there was no effect of
      age on signal duration. Cartilage surfaces of all specimens were smooth and no
      degenerative changes were macroscopically or microscopically evident. The surface
      brightness of cartilage under the polarized light microscope was consistent with
      signal intensity values. CONCLUSIONS: The response of articular cartilage to
      ultrasound was maturation-dependent. Acoustic properties differed from mechanical
      stiffness properties, which were determined using indentation. Ultrasound may
      detect properties of the surface collagen of the articular cartilage.

PMID- 16563813
TI  - Expression of superficial zone protein in mandibular condyle cartilage.
AB  - OBJECTIVE: Superficial zone protein (SZP) has been shown to function in the
      boundary lubrication of articular cartilages of the extremities. However, the
      expression of SZP has not been clarified in mandibular cartilage which is a
      tissue that includes a thick fibrous layer on the surface. This study was
      conducted to clarify the distribution of SZP on the mandibular condyle and the
      regulatory effects of humoral factors on the expression in both explants and
      fibroblasts derived from mandibular condyle. METHODS: The distribution of SZP was
      determined in bovine mandibular condyle cartilage, and the effects of interleukin
      1beta (IL-1beta) and transforming growth factor-beta (TGF-beta) on SZP expression
      were examined in condyle explants and fibroblasts derived from the fibrous zone
      of condyle cartilage. RESULTS: SZP was highly distributed in the superficial zone
      of intact condyle cartilage. The SZP expression was up-regulated by TGF-beta in
      both explants and cultured fibroblasts, whereas the expression was slightly down
      regulated by IL-1beta. A significant increase in accumulation of SZP protein was
      also observed in the culture medium of the fibroblasts treated with TGF-beta.
      CONCLUSIONS: These results suggest that SZP plays an important role in boundary
      lubrication of mandible condylar cartilage, is synthesized locally within the
      condyle itself, and exhibits differential regulation by cell mediators relevant
      to mandibular condyle repairing and pathologies.

PMID- 16563814
TI  - RNA delivery by heat shock protein-70 into mammalian cells: a preliminary study.
AB  - Heat shock proteins (Hsps) are ubiquitous molecular chaperones with indispensable
      roles in assisting protein folding and giving protection from proteotoxic
      environmental harm. Members of the 70-kDa heat shock protein family have been
      demonstrated to recognize and bind with distinguished RNA sequences, which
      function as determinants of eukaryotic mRNA stability. We have earlier identified
      the molecular domains involved in RNA-binding and characterized in detail the
      specificity, affinity and some regulatory aspects of this molecular interaction
      using various deletion mutants and homologues of Hsp70. We have shown that wild
      type, but not any of the tested truncated mutants of Hsp70, is efficiently taken
      up by P388 mouse macrophage cells. Here we addressed the question of whether
      Hsp70 is capable of delivering bound RNA into mammalian cells. Employing
      fluorescence and confocal microscopy, we demonstrated that full length Hsp70
      facilitates the uptake of RNA molecules into the cytoplasm of mammalian cells. We
      propose that further optimization of this system might enable the development of
      a valuable tool to deliver RNA molecules, such as siRNA, dsRNA or other
      regulatory RNA sequences to probe or influence various regulatory processes in
      eukaryotic cells.

PMID- 16563815
TI  - Thrombotic complications in essential thrombocythemia (ET): clinical facts and
      biochemical riddles.
AB  - Hemostatic complications which can occur in the arterial or venous vasculature or
      in the microcirculation are the major causes of morbidity and mortality in
      patients with ET. In order to prevent these complications, often platelet
      reductive drugs are used. These agents are by themselves potentially toxic, i.e.
      may cause leukemia or cardiac side effects. In order to avoid these adverse
      effects, a better understanding of the mechanism of thrombus formation which is
      causative in ET is mandatory. Unfortunately, until now, no biomarkers have been
      identified which allow the estimation of the risk of thrombotic complications.
      Platelet number is not a good predictor per se since thrombotic complications can
      occur in some patients at low platelet numbers whereas others do not encounter a
      thrombosis even at very high platelet levels. On the other hand, lowering of the
      platelet count usually results in symptomatic improvement. In ET, morphological
      alterations of the megakaryocyte in the bone marrow and the circulating platelets
      are observed: megakaryocyte nuclei show a staghorn appearance, circulating
      platelets are characterized by anisocytosis and giant size. Functional studies
      indicate that these anatomically altered platelets function abnormally. When
      platelets are analyzed with a platelet function analyzer (PFA-100, which uses
      cartridges that measure how well a patient's platelets adhere and aggregate to
      form a platelet plug in the first phase of thrombus formation), in many patients
      with ET, closure time using collagen/ADP and collagen/epinephrine cartridges is
      prolonged. This seems paradoxical since these patients do not show an increased
      bleeding time. These results indicate that either receptors and/or consecutive
      signaling events are abnormal in ET platelets. Proteomic analysis of platelets of
      ET patients has revealed individual differences but not yet led to the
      identification of disease-specific proteins. Moreover, the search for alternative
      risk factors (factor V Leiden, prothrombin gene polymorphism, etc.) has not
      provided evidence for the contribution of these factors to the generation of the
      thrombotic risk in ET patients. In summary, despite intensive research over
      several decades, relatively little is known about the pathogenesis and risk
      factors for thrombosis in ET. I expect that this conference will contribute to
      the development of new strategies to identify patients at risk for hemostatic
      complications.

PMID- 16563816
TI  - Fertilization in plants: is calcium a key player?
AB  - For many years, the physiological significance of Ca(2+) oscillations has been a
      matter of debate, but the potential to encode and transduce information in the
      pattern of an oscillation is obvious. In this review, we only consider transients
      and oscillations observed during fertilization in plants with the major focus on
      flowering plants. After presenting data related to algae, fertilization
      mechanisms in flowering plants are defined as a multi-step phenomenon, starting
      with pollination during which calcium plays a key role, especially during pollen
      stigma interactions (compatible and incompatible reactions). The pollen tube
      serves as a guide and a pathway for the sperm cells on their course towards their
      female target cells. For many years, the pollen tube has also been studied as an
      easily accessible in vitro model to elucidate the role of calcium on tip growth.
      Finally, in flowering plants, a unique double fertilization system is present.
      Interesting data obtained from an in vitro fertilization system in maize are
      presented and discussed. In addition, the new approaches made possible by
      Arabidopsis and Torenia and their potential limitations are covered.

PMID- 16563817
TI  - Sleep homeostasis in primary insomnia.
AB  - Three main factors, hyperarousal, circadian dysrhythmia, and homeostatic
      dysregulation, are thought to underlie chronic insomnia. To date, most of the
      empirical work has focused on the issue of hyperarousal and very little work has
      been undertaken on the issue of sleep homeostasis. In the present paper, we
      review the five lines of evidence which may be used to support the proposition
      that sleep homeostasis is altered in Primary Insomnia. These include findings
      pertaining to Slow Wave Sleep density, level of daytime sleepiness, sleepiness
      following sleep deprivation, recovery sleep following sleep deprivation, and
      response to sleep restriction therapy. In addition, we provide a discussion
      regarding how hyperarousal and circadian factors may interact with altered sleep
      homeostasis, and suggestions for further inquiry.

PMID- 16563818
TI  - Cardioprotective effects of vegetables: is nitrate the answer?
AB  - A diet rich in fruits and vegetables is associated with a lower risk of certain
      forms of cancer and cardiovascular disease, but the mechanisms behind this
      protection are not completely understood. Recent epidemiological studies suggest
      a cardioprotective action afforded specifically by green leafy vegetables. We
      here propose that these beneficial effects are related to the high content of
      inorganic nitrate, which in concert with symbiotic bacteria in the oral cavity is
      converted into nitrite, nitric oxide, and secondary reaction products with
      vasodilating and tissue-protective properties.

PMID- 16563819
TI  - Cross-sectional evaluation of patient functioning and health-related quality of
      life in patients with neuropathic pain under standard care conditions.
AB  - AIM: The purpose of this cross-sectional evaluation was to determine the impact
      of neuropathic pain (NeP) on patient functioning and Health-Related Quality of
      Life (HRQoL) under standard care conditions. METHODS: Patients with NeP or
      neuropathic and nociceptive pain [Mixed Pain (MP)] enrolled in the DONEGA study,
      a naturalistic, prospective and multi-centre study of the effectiveness of
      gabapentin under usual care conditions, were included in this cross-sectional
      evaluation before starting study treatments. Participants completed the Short
      Form-McGill Pain Questionnaire, MOS Short Form-12 (SF-12), and Sheehan Disability
      Scale (ShDS). Multivariate analysis and regression models were used to analyze
      patient data. RESULTS: A total of 1519 patients [mean+/-SD; 56.0+/-13.7 yrs old
      (58.8% female)] with NeP or MP were enrolled in the study. The mean pain history
      was 1.1+/-2.8 yrs, current pain intensity on a 5-point visual analogue scale was
      2.8+/-1.0 and mean pain in previous week was 71.3+/-19.0mm. Pain substantially
      interfered (i.e., score > or = 5 on 0-10 scale) with normal work (5.9+/-3.0),
      social life (5.7+/-3.0), and family life (5.3+/-3.0), producing substantial
      disability (total ShDS score of 16.9+/-8.3 pts). Country-standardised physical
      (PCS) and mental health (MCS) component summary scores of SF-12 indicated
      significant impairment in both domains compared with the general Spanish
      population: PCS; -1.13+/-1.0 SDS (standard deviation score), and MCS; -1.21+/-0.7
      SDS, equivalent to the 15th and 25th percentiles of normative populations,
      respectively. CONCLUSIONS: Under standard care conditions, neuropathic and mixed
      pain are associated with impaired physical and mental QoL, producing a
      substantial level of disability in these patients.

PMID- 16563820
TI  - (1)H-(13)C INEPT MAS NMR correlation experiments with (1)H-(1)H mediated
      magnetization exchange to probe organization in lipid biomembranes.
AB  - Two-dimensional (1)H-(13)C INEPT MAS NMR experiments utilizing a (1)H-(1)H
      magnetization exchange mixing period are presented for characterization of lipid
      systems. The introduction of the exchange period allows for structural
      information to be obtained via (1)H-(1)H dipolar couplings but with (13)C
      chemical shift resolution. It is shown that utilizing a RFDR recoupling sequence
      with short mixing times in place of the more standard NOE cross-relaxation for
      magnetization exchange during the mixing period allowed for the identification
      and separation of close (1)H-(1)H dipolar contacts versus longer-range inter
      molecular (1)H-(1)H dipolar cross-relaxation. These 2D INEPT experiments were
      used to address both intra- and inter-molecular contacts in lipid and
      lipid/cholesterol mixtures.

PMID- 16563821
TI  - Assessment of diffusion coefficients of general solvents by PFG-NMR:
      investigation of the sources error.
AB  - Accurate measurements of the diffusion coefficients, including an estimate of
      uncertainty, of various solvent molecules using the PFG-NMR method were performed
      in this study. Accurate diffusion coefficients were obtained using the Shigemi
      NMR tube. The relative combined standard uncertainties of the diffusion
      coefficients were found to be within approximately 0.4%. The three uncertainty
      sources (signal decay of the standard and the solvent, and diffusion coefficient
      of standard) equally affect the combined standard uncertainties. Unreliable data
      were obtained using a normal NMR tube, indicating that convection and background
      gradient effects significantly affected the accurate measurement of the diffusion
      coefficients.

PMID- 16563822
TI  - New methods for calibration of the RF field strength for indirectly observed
      nuclei.
AB  - Two novel pulse sequences, CALIS-1 and CALIS-2, for accurate calibration of the
      RF field strength for an indirectly observed spin are introduced. CALIS-2 is
      intended for calibration of e.g., (13)C or (15)N pulses on natural abundance
      samples whilst CALIS-1 is recommended primarily for enriched samples. Both
      experiments can be performed without prior knowledge or guess of the RF field
      strength and no delays in the pulse sequences are critically dependent on
      coupling constants.

PMID- 16563823
TI  - Prediction of h5-HT2A receptor antagonistic activity of arylindoles:
      computational approach using topochemical descriptors.
AB  - Relationship between the topochemical indices and h5-HT2A receptor antagonistic
      activity of arylindoles has been investigated. Three topochemical indices,
      Wiener's topochemical index--a distance-based topochemical descriptor, molecular
      connectivity topochemical index--an adjacency-based topochemical descriptor and
      eccentric connectivity topochemical index--an adjacency-cum-distance based
      topochemical descriptor, were used for the present investigation. A data set
      comprising 31 differently substituted arylindoles was selected for the present
      study. The values of the Wiener's topochemical index, molecular connectivity
      topochemical index and eccentric connectivity topochemical index were computed
      for all the analogues involved in the data set using an in-house computer
      program. Resultant data was analyzed and suitable models were developed after
      identification of the active ranges. Subsequently, a biological activity was
      assigned to each analogue using these models, which was then compared with the
      reported h5-HT2A receptor antagonistic activity. Accuracy of prediction was found
      to vary from a minimum of approximately 81% to a maximum of approximately 84%.

PMID- 16563824
TI  - Techniques for visualization of carbohydrate molecules.
AB  - Standard molecular visualizations, such as the classic ball-and-stick model, are
      not suitable for large, complex molecules because the overall molecular structure
      is obscured by the atomic detail. For proteins, the more abstract ribbon and
      cartoon representations are instead used to reveal large scale molecular
      conformation and connectivity. However, there is currently no accepted convention
      for simplifying oligo- and polysaccharide structures. We introduce two novel
      visualization algorithms for carbohydrates, incorporated into a visualization
      package, CarboHydra. Both algorithms highlight the sugar rings and backbone
      conformation of the carbohydrate chain, ignoring ring substituents. The first
      algorithm, termed PaperChain, emphasizes the type and conformation of the
      carbohydrate rings. The second, Twister, emphasizes the relative orientation of
      the rings. We further include two rendering enhancements to augment these
      visualizations: silhouettes edges and a translucent overlay of the ball-and-stick
      atomic representation. To demonstrate their utility, the algorithms and
      visualization enhancements are here applied to a variety of carbohydrate
      molecules. User evaluations indicate that they present a more useful view of
      carbohydrate structure than the standard ball-and-stick representation. The
      algorithms were found to be complementary, with PaperChain particularly effective
      for smaller carbohydrates and Twister useful at larger scales for highlighting
      the backbone twist of polysaccharides.

PMID- 16563825
TI  - Osmoregulation and Na,K-ATPase expression in osmoregulatory organs of Scylla
      paramamosain.
AB  - Scylla paramamosain is a euryhaline marine crab that can actively regulate its
      osmotic pressure of the hemolymph. We investigated the expression of Na,K-ATPase
      in the osmoregulatory organs, including anterior gills, posterior gills, antennal
      glands, and midgut. Our cDNA sequencing of the Na,K-ATPase alpha-subunit revealed
      no isoforms in any of the four osmoregulatory organs studied. The full-length
      cDNA contains 3,866 bp that encode a complete open reading frame of 1,039 amino
      acids. The osmotic pressure of the hemolymph changed immediately after
      transference from 25 ppt to 5 and 45 ppt, and reached a new steady state within 3
      days, showing the typical pattern of weak hyperosmoregulators. Expression of Na,K
      ATPase alpha-subunit mRNA level was determined for individuals acclimated in 5,
      25, and 45 parts per thousand (ppt) for 7 days. Compared to the mRNA level of
      those from 25 ppt, the level in the posterior gills from 5 ppt was significantly
      higher. Also, the mRNA levels in the anterior gills, posterior gills and antennal
      glands from 45 ppt were significantly higher than that of the respective organs
      in 25 ppt. This increase in the 5 ppt treatment may be responsible for the
      observed increase of Na,K-ATPase activity on day 14 when the posterior gills had
      a significantly higher activity than those in the other two salinity treatments.
      No difference was found in the protein level across salinities. In conclusion,
      the posterior gills play the most important role in osmoregulation in dilute
      seawater and the increase in Na,K-ATPase activity on the 7th day may be due to
      its gene transcription and/or mRNA translation.

PMID- 16563827
TI  - cDNA cloning and characterization of Type I procollagen alpha1 chain in the skate
      Raja kenojei.
AB  - A full-length cDNA of the Type I procollagen alpha1 [pro-alpha1(I)] chain (4388
      bp), coding for 1463 amino acid residues in the total length, was determined by
      RACE PCR using a cDNA library constructed from 4-week embryo of the skate Raja
      kenojei. The helical region of the skate pro-alpha1(I) chain consisted of 1014
      amino acid residues - the same as other fibrillar collagen alpha chains from
      higher vertebrates. Comparison on denaturation temperatures of Type I collagens
      from the skate, rainbow trout (Oncorhynchus mykiss) and rat (Rattus norvegicus)
      revealed that the number of Gly-Pro-Pro and Gly-Gly in the alpha1(I) chains could
      be directly related to the thermal stability of the helix. The expression
      property of the skate pro-alpha1(I) chain mRNA and phylogenetic analysis with
      other vertebrate pro-alpha1(I) chains suggested that skate pro-alpha1(I) chain
      could be a precursor form of the skate Type I collagen alpha1 chain. The present
      study is the first evidence for the primary structure of full-length pro
      alpha1(I) chain in an elasmobranch.

PMID- 16563826
TI  - Real-time PCR analysis of ovary- and brain-type aromatase gene expression during
      Atlantic halibut (Hippoglossus hippoglossus) development.
AB  - Two forms of cytochrome P450 aromatase, acting in both the brain and the ovary,
      have been implicated in controlling ovarian development in fish. To better
      understand the expression of these two enzymes during sexual differentiation in
      Atlantic halibut (Hippoglossus hippoglossus), real-time PCR was used to quantify
      the mRNA levels of ovary- (cyp19a) and brain-type cytochrome P450 aromatase
      (cyp19b) genes in the gonad and brain during gonadal development. Both enzymes
      showed high levels of expression in both tissues in developmental stages prior to
      histologically detectable ovarian differentiation (38 mm fork length), with
      increased expression occurring slightly earlier in the brain than the gonad.
      Cyp19a showed a second peak of expression in later stages (> 48 mm) in the gonad,
      but not the brain. Cyp19b expression was generally higher in the brain than the
      gonad. These results suggest that sexual differentiation may begin in the brain
      prior to gonadal differentiation, supporting the idea that steroid hormone
      expression in the brain is a key determinant of phenotypic sex in fish. In an
      examination of sexually immature adults, cyp19a was highly expressed in female
      gonad while cyp19b was very highly expressed in the pituitary of both sexes. The
      ratio of cyp19a to cyp19b expression was much higher in ovaries than in testes in
      the adult fish, so this ratio was analyzed in the developing gonads of juvenile
      halibut in an attempt to infer their sex. This was only partially successful,
      with about half the fish in later developmental stages showing apparently sex
      specific differences in aromatase expression.

PMID- 16563828
TI  - The Escherichia coli AmtB protein as a model system for understanding ammonium
      transport by Amt and Rh proteins.
AB  - The Escherichia coli ammonium transport protein (AmtB) has become the model
      system of choice for analysis of the process of ammonium uptake by the ubiquitous
      Amt family of inner membrane proteins. Over the past 6 years we have developed a
      range of genetic and biochemical tools in this system. These have allowed
      structure/function analysis to develop rapidly, offering insight initially into
      the membrane topology of the protein and most recently leading to the solution of
      high-resolution 3D structures. Genetic analysis has revealed a novel regulatory
      mechanism that is apparently conserved in prokaryotic Amt proteins and genetic
      approaches are also now being used to dissect structure/function relationships in
      Amt proteins. The now well-recognised homology between the Amt proteins, found in
      archaea, eubacteria, fungi and plants, and the Rhesus proteins, found
      characteristically in animals, also means that studies on E. coli AmtB can
      potentially shed light on structure/function relationships in the clinically
      important Rh proteins.

PMID- 16563829
TI  - Transport characteristics of mammalian Rh and Rh glycoproteins expressed in
      heterologous systems.
AB  - The development and use of heterologous expression systems is critical for
      deciphering the function of mammalian Rh and Rh-glycoproteins. The studies here
      use Xenopus oocytes, well known for their ability to readily traffic and express
      difficult membrane proteins, and S. cerevisiae wild-type strains and mutants that
      are defective in ammonium transport. Data obtained in both of these expression
      systems revealed that mammalian Rh-glycoprotein-mediated transport (RhAG, RhBG,
      and RhCG) is an electroneutral process that is driven by the NH4+ concentration
      and the transmembrane H+ gradient, effectively exchanging NH4+ for H+ in a
      process that results in transport of net NH3. Homology modeling and functional
      studies suggest that the more recently evolved erythrocyte blood group proteins,
      RhCE and RhD, may not function directly in ammonia transport and may be evolving
      a new function in the RBC membrane. The relationship of Rh and Rh-glycoproteins
      to the Amt/Mep ammonium transporters is substantiated with functional transport
      data and structural modeling.

PMID- 16563830
TI  - Ion transport versus gas conduction: function of AMT/Rh-type proteins.
AB  - Although lipid membranes exhibit some permeability to the weak base NH3,
      organisms have developed specialized proteins that increase and regulate the NH3
      fluxes across cellular membranes. In humans, the Rh glycoproteins, such as the
      erythrocyte-specific RhAG and the liver and kidney homologs RhBG and RhCG, are
      involved in the passage of NH3. Rh glycoproteins have distant relatives, called
      ammonium transporters (AMTs), in archae and bacteria. The crystal structures of
      AMTs show that the proteins are homo-trimers and that the center of each monomer
      forms a pore. AMT/Rh proteins have also been identified in plants. In contrast to
      the human Rh glycoproteins, these AMTs specifically transport NH4+ or co
      transport NH3/H+. Hence, they can transport against NH3 gradients. The molecular
      determinants for the different transport mechanisms within proteins of the same
      family are currently unclear. The functional differences between AMT/Rh
      transporters are likely to be an evolutionary adaptation to different ammonium
      and nitrogen requirements in bacteria, plants and animals.

PMID- 16563831
TI  - Rh glycoproteins in epithelial cells: lessons from rat and mice studies.
AB  - Rhesus glycoproteins are a recently discovered family of ammonium transporters
      and a new branch of the Mep/AMT proteins superfamily that was identified more
      than 15 years ago in lower organisms and plants. Despite many ex vivo studies
      showing evidences that Rh glycoproteins can accelerate transmembrane NH3 or NH4+
      transfer, their role in normal and disease physiology remains unknown. This
      review focuses on some of the different studies carried out in animal models to
      gain insight into Rh glycoprotein function. Immunolocalization studies have added
      new evidence that this protein family is related to ammonium transport or
      metabolism in epithelial cells. However, the absence of distal tubular acidosis
      or hyperammonemia in Rhbg KO mice have raised new questions about the
      physiological significance of these proteins.

PMID- 16563832
TI  - Molecular genetics of RH and its clinical application.
AB  - BACKGROUND: The RH genes RHD and RHCE encode two proteins that represent the
      clinically most important blood group system defined by the sequences of red cell
      membrane proteins. In the last five years the field has been moving from defining
      the underlying molecular genetics to applying the molecular genetics in clinical
      practice. MATERIALS AND METHODS: The state of the current knowledge is briefly
      summarized using recent reviews and original work since 2000. RESULTS: The RHD
      and RHCE genes are strongly homologous and located closely adjacent at the human
      chromosomal position 1p36.11. Part of the genetic complexity is explained by the
      clustered orientation of both genes with their tail ends facing each other. The
      SMP1 gene is located interspersed between both RH genes. Using additional genetic
      features of the RH gene locus, RHCE was shown to represent the ancestral RH
      position, while RHD is the duplicated gene. More than 150 alleles have been
      defined for RHD alone. They were classified based on antigenic and clinical
      properties into phenotypes like partial D, weak D and DEL. Among the D negative
      phenotype a large variety of non-functional alleles were found. The frequencies
      of these distinct alleles vary widely among human populations, which has
      consequences for clinical practice. CONCLUSION: Rhesus is a model system for the
      correlation of genotype and phenotype, facilitating the understanding of
      underlying genetic mechanisms in clustered genes. With regard to clinical
      practice, the genetic diagnostics of blood group antigens will advance the cost
      effective development of transfusion medicine.

PMID- 16563833
TI  - Biological gas channels for NH3 and CO2: evidence that Rh (Rhesus) proteins are
      CO2 channels.
AB  - Physiological evidence from our laboratory indicates that Amt/Mep proteins are
      gas channels for NH3, the first biological gas channels to be described. This
      view has now been confirmed by structural evidence and is displacing the previous
      belief that Amt/Mep proteins were active transporters for the NH4+ ion. Still
      disputed is the physiological substrate for Rh proteins, the only known
      homologues of Amt/Mep proteins. Many think they are mammalian ammonium (NH4+ or
      NH3) transporters. Following Monod's famous dictum, "Anything found to be true of
      E. coli must also be true of elephants" [Perspect. Biol. Med. 47(1) (2004) 47],
      we explored the substrate for Rh proteins in the unicellular green alga
      Chlamydomonas reinhardtii. C. reinhardtii is one of the simplest organisms to
      have Rh proteins and it also has Amt proteins. Physiological studies in this
      microbe indicate that the substrate for Rh proteins is CO2 and confirm that the
      substrate for Amt proteins is NH3. Both are readily hydrated gases. Knowing that
      transport of CO2 is the ancestral function of Rh proteins supports the inference
      from hematological research that a newly evolving role of the human Rh30
      proteins, RhCcEe and RhD, is to help maintain the flexible, flattened shape of
      the red cell.

PMID- 16563834
TI  - Red cell membrane CO2 permeability in normal human blood and in blood deficient
      in various blood groups, and effect of DIDS.
AB  - The red cell membrane has an exceptionally high permeability for CO2, PCO2
      approximately 0.15 cm/s, which is two to three orders of magnitude greater than
      that of some epithelial membranes and similarly greater than the permeability of
      the red cell membrane for HCO3-. As shown previously, this high PCO2 can be
      drastically inhibited by 10 microM 4,4'-diisothiocyanato-2,2'-stilbenedisulfonate
      (DIDS), indicating that membrane proteins may be involved in this high gas
      permeability. Here, we have studied the possible contribution of several blood
      group proteins to CO2 permeation across the red cell membrane by comparing PCO2
      of red cells deficient in specific blood group proteins with that of normal red
      cells. While PCO2 of normal red cells is approximately 0.15 cm/s and that of
      Fy(null) and Jk(null) red cells is similar, PCO2's of Colton null (deficient in
      aquaporin-1) and Rh(null) cells (deficient in Rh/RhAG) are both reduced to about
      0.07 cm/s, i.e. to about one half. In addition, the inhibitory effect of DIDS is
      about half as great in Rh(null) and in Colton null red cells as it is in normal
      red cells. We conclude that aquaporin-1 and Rh/RhAG proteins contribute
      substantially to the high permeability of the human red cell membrane for CO2.
      Together these proteins are responsible for 50% or more of the CO2 permeability
      of red cell membranes. The CO2 pathways of both proteins can be partly inhibited
      by DIDS, which is why this compound very effectively reduces membrane CO2
      permeability.

PMID- 16563835
TI  - [Identification strategy of RHCE gene variants at the National Blood Group
      Reference Laboratory: impact on transfusion safety].
AB  - The RH blood group is the most polymorphic and immunogenic blood group system.
      The RH locus is composed of 2 highly homologous genes: the RHD gene encoding the
      D polypeptide; and the RHCE gene, encoding C or c together with either E or e
      polypeptides. Numerous variants exist for both RHD and RHCE genes. Among them we
      were interested in the serological and molecular definition of numerous pre
      published RHCE variants encountered in different populations. The identification
      of these variants is crucial to ensure the transfusion safety for patients
      expressing these variants. Here we propose a procedure to identify some of them
      and discuss the adequate transfusion strategy. This procedure has enable us to
      identify new variants to be presented at the symposium.

PMID- 16563836
TI  - Recent developments in fetal nucleic acids in maternal plasma: implications to
      noninvasive prenatal fetal blood group genotyping.
AB  - The discovery of circulating cell-free fetal DNA in maternal plasma has opened up
      new possibilities for noninvasive prenatal diagnosis. Fetal DNA in maternal
      plasma has been used for the noninvasive prenatal determination of the RhD status
      of fetuses carried by RhD-negative pregnant women. In such analysis, the possible
      need of an internal control for the presence of detectable amounts of fetal DNA
      in a particular maternal plasma sample has been actively discussed. Recently, the
      development of a robust method for discriminating single nucleotide differences
      in plasma DNA using single allele base extension reaction (SABER) followed by
      matrix-assisted laser-desorption and ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) has opened up the possibilities of using a panel of single
      nucleotide polymorphisms as such a positive control. A second approach is the
      recent successful development of fetal epigenetic markers which can be developed
      into universal fetal DNA markers. These developments hold promise to allow the
      eventual widespread utilization of maternal plasma DNA analysis for the
      noninvasive prenatal diagnosis of blood group mismatches between the mother and
      fetus.

PMID- 16563837
TI  - Comments on the original article by Philippe Zangger et al. entitled: "asymmetry
      of small joint involvement in rheumatoid arthritis: prevalence and tendency
      towards symmetry over time".

PMID- 16563838
TI  - Metastatic malignant melanoma in a patient taking interleukin-1 receptor
      antagonist.

PMID- 16563839
TI  - Evaluating vitamin D status. Implications for preventing and managing
      osteoporosis and other chronic diseases.
AB  - Recent studies have added new dimensions to the fund of knowledge on vitamin D.
      In addition to the classic role of vitamin D in preventing rickets and
      osteomalacia, a preventive effect against osteoporotic fractures has been
      convincingly established, and abundant evidence suggests a role in preventing
      malignancies and autoimmune diseases. Serum 25-OH-vitamin D assay is a simple
      test for evaluating vitamin D status. However, recent review articles indicate
      that current reference ranges for serum 25-OH-vitamin D are too low. An
      appropriate lower normal limit may be between 50-100 nmol/l (20-40 ng/ml).
      Standard supplement dosages may fail to provide concentrations above this range.

PMID- 16563842
TI  - Radiological examination in low back pain patients: anxiety of the patient?
      Anxiety of the therapist?
AB  - A review of the recent literature shows that guidelines on the management of low
      back pain (LBP) have little impact on the use of radiological imagery. Among the
      factors which might account for the use of radiological examination, a review of
      the literature points to some that refer to the patient, others to the clinician
      and still others to the therapeutic interaction. This leads one to question the
      importance of radiological examination for both the patient and the physician.
      The matter at stake in this review is the relationship that may exist between
      this type of examination and the patient's and/or the physician's anxiety. If
      these aspects are associated or causally related, this relationship can be two
      sided and is thus susceptible to affect the patient, the physician, or both. Some
      possible keys which emphasize the central role of the therapeutic relationship in
      this predicament are also reviewed.

PMID- 16563840
TI  - Intermittent parathyroid hormone therapy to increase bone formation.
AB  - Clinical data suggested that parathyroid hormone (PTH) might be effective in
      improving bone mass in patients with osteoporosis, providing its resorptive
      effects, which are particularly marked at cortical sites, were kept under
      control. We reviewed the evidence that intermittent PTH therapy is a valid
      treatment option whose predominant effect is bone anabolism. In cell culture
      studies, PTH affected both bone formation and bone resorption, suggesting that
      the net result of PTH therapy may be either bone gain or bone loss depending on
      the dosage, mode of administration, bone site, and animal species. Histological
      studies established that intermittent PTH therapy was associated with an increase
      in trabecular bone and, importantly, with improvements in trabecular and cortical
      microarchitectural parameters that have not been reported with antiresorptive
      drugs. This anabolic effect of intermittent PTH therapy translates into increased
      biomechanical strength, despite the increase in endocortical porosity seen in
      humans and nonhuman primates. The biochemical response profile to intermittent
      PTH therapy in clinical trials indicated a phase of isolated anabolism followed
      by an overall increase in bone remodeling that predominantly affected bone
      formation, the result being a large increase in spinal bone mineral density as
      early as the first treatment year. Thus, intermittent PTH therapy exerts
      predominantly anabolic effects on bone.

PMID- 16563843
TI  - A rare European case of Madura Foot due to actinomycetes.
AB  - We present a case of mycetoma by Actinomadura spp. on the foot of an Albanian
      young man arrived to our observation approximately 5 years after the first
      clinical manifestations (hard tumefaction, slightly painful upon weight-bearing
      and palpation and cutaneous fistulas that discharged an abundant granulomatous
      secretion). Direct microscopic analysis and culture of the white-yellowish grains
      included Gram staining, which showed extensively branched Gram-positive hyphae
      less than 1 mm in diameter, allowing to make a diagnosis of Actinomycetoma. Since
      Actinomycetoma is sensitive to drug treatment, the patient was given trimethoprim
      sulfamethoxazole and amikacin twice daily for 45 days. After six months of
      chemotherapy, the patient's general condition improved, the swelling is slightly
      diminished and grain extrusion has ceased. The patient has been able to resume
      ambulation with normal footwear. Given the absence of liver and kidney functional
      alterations, the patient is scheduled to continue pharmacological treatment with
      trimethoprim-sulfamethoxazole.

PMID- 16563844
TI  - Appropriate and inappropriate use of oral glucocorticoid therapy in rheumatoid
      arthritis.

PMID- 16563845
TI  - Ultrasound promoted regioselective nitration of phenols using dilute nitric acid
      in the presence of phase transfer catalyst.
AB  - Phenols are selectively nitrated to o-nitrophenol along with rate enhancement
      using dilute nitric acid (6 wt%)/tetra butyl ammonium bromide (TBAB) under
      sonication. The selectivity can also be reversed to p-nitrophenol using NaBr as a
      catalyst. Kinetic analysis of nitration of phenol both with and without
      sonication has been investigated by variation of reaction parameters such as
      catalyst, nitric acid and substrate concentration.

PMID- 16563846
TI  - Removal of disperse blue 2BLN from aqueous solution by combination of ultrasound
      and exfoliated graphite.
AB  - This paper reports an efficient and convenient removal of disperse blue 2BLN from
      aqueous solution by the combination of ultrasound and exfoliated graphite. The
      various affecting factors were studied. The removal ratio of disperse blue 2BLN
      is 96.9% for the initial concentration of 200 mg/L using 600 mg/L exfoliated
      graphite (exfoliation volume of 300 mL/g) at 45 degrees C within 120 min under
      ultrasound. The combination method was more effective than sonolysis or
      exfoliated graphite treatment individually.

PMID- 16563847
TI  - Biomechanical analysis of cages for posterior lumbar interbody fusion.
AB  - Interbody fusions using intervertebral cages have become increasingly common in
      spinal surgery. Computational simulations were conducted in order to compare
      different cage designs in terms of their biomechanical interaction with the
      spinal structures. Differences in cage design and surgical technique may
      significantly affect the biomechanics of the fused spine segment, but little
      knowledge is available on this topic. In the present study, four 3D finite
      element models were developed, reproducing the human L4-L5 spinal unit in intact
      condition and after implantation of three different cage models. The intact model
      consisted of two vertebral bodies and relevant laminae, facet joints, main
      ligaments and disc. The instrumented models reproduced the post-operative
      conditions resulting after implant of the different cages. The three considered
      devices were hollow threaded titanium cages, the BAK (Zimmer Centerpulse, Warsaw,
      IN, USA), the Interfix and the Interfix Fly (both by Medtronic Sofamor Danek,
      Memphis, TN, USA). Simulations were run imposing various loading conditions,
      under a constant compressive preload. A great increase in the stiffness induced
      on the spinal segment by all cages was observed in all the considered loading
      cases. Stress distributions on the bony surface were evaluated and discussed. The
      differences observed between the biomechanics of the instrumented models were
      associated with the geometrical and surgical features of the devices.

PMID- 16563848
TI  - Evidence-based forensic sampling - more questions than answers.

PMID- 16563849
TI  - The journal, special issues & evidence.

PMID- 16563850
TI  - Impaired decision-making in Parkinson's disease.
AB  - The present study demonstrated that individuals with Parkinson's disease display
      impairments in making profitable decisions, as evidenced by poorer performance on
      the Iowa Gambling Task relative to matched controls. The ability to make
      beneficial judgments solely correlates with ability to appropriately attribute
      internal mental-state to other people, as shown in a mind-reading task. However,
      decision-making ability for individuals with Parkinson's disease is not
      associated with effective execution, intellectual function or depressed mood.
      These findings offer a new perspective on the cognitive impairments that affect
      social living and adaptive decisions for individuals with Parkinson's disease.

PMID- 16563851
TI  - Urban-rural differentials in child malnutrition: trends and socioeconomic
      correlates in sub-Saharan Africa.
AB  - This paper examines levels and trends of urban-rural differentials in child
      malnutrition, and investigates whether residual differences exist between urban
      and rural areas, given comparable measures of socioeconomic status (SES) of
      households and communities. Using data from Demographic and Health Surveys of 15
      sub-Saharan African countries, and multilevel modelling, it shows that urban
      rural differentials are considerable in all countries, that they have narrowed in
      most countries due primarily to an increase in urban malnutrition, and have
      widened in few countries as a result of sharp decline in urban malnutrition.
      These urban-rural gaps are abolished in almost all countries when SES is
      controlled. These results suggest that policies and programs contributing to the
      attainment of the MDGs should pay particular attention to the urban poor.

PMID- 16563852
TI  - Spectroscopic and electrochemical studies of hetero-bimetallic copper complexes
      with Schiff's base ligand.
AB  - Using Schiff's base ligand, several Cu(II) based bimetallic complexes such as Cu
      Cu, Cu-Co, Cu-Ni, Cu-Zn, Cu-Mn have been prepared in a stepwise procedure. The
      structures of these complexes and the ligand have been proposed on the basis of
      FAB mass, elemental analysis, UV-vis, IR, electron paramagnetic resonance (EPR)
      and CV studies. EPR parameters, obtained through complete simulation, suggest
      that the formation of bimetallic complexes forces the Cu(II) centre to increase
      the flexibility in comparison with the monometallic Cu(II) complex. However, the
      nature of the second metal ion in the bimetallic complex effects the distortion
      around the first metal ion. The reduction of the complexes from Cu(II) to Cu(I)
      involves a large geometrical change and is found to be irreversible. A large
      positive shift is seen in the cathodic process, which can be ascribed to
      increased distortion due to bimetallic coordination. These complexes have
      potential usage in DNA studies.

PMID- 16563853
TI  - A new chemiluminescence method for the determination of nickel ion.
AB  - A new chemiluminescence (CL) phenomenon described as the second-chemiluminescence
      (SCL) was observed and a strong CL signal was detected, when Ni(II) ion was
      injected into the mixture after the end of the reaction of potassium permanganate
      with alkaline luminol. The possible CL mechanism is proposed based on the kinetic
      curve of the CL reaction, CL spectra, UV-vis spectra and some other experiments.
      A flow-injection analysis for the determination of nickle(II) ion has been
      developed, based on the catalysis of nickel(II) ion on the CL reaction between
      potassium manganate produced on-line and luminol under alkaline condition. Under
      the optimum conditions, the SCL intensity is linear with the concentration of
      nickel(II) ion in the range of 8.0-200.0 microg l-1 and 0.2-2.0 mg l-1. The
      R.S.D. was 4.5% for 11 determinations of 250 microg l-1 nickel(II) ion and the
      detection limit (3sigma) for nickel(II) ion was 0.33 microg l-1. The method was
      applied to determine nickel(II) ion in synthetic samples with satisfactory
      results.

PMID- 16563854
TI  - Natural gas pipeline leak detector based on NIR diode laser absorption
      spectroscopy.
AB  - The paper reports on the development of an integrated natural gas pipeline leak
      detector based on diode laser absorption spectroscopy. The detector transmits a
      1.653 microm DFB diode laser with 10 mW and detects a fraction of the backscatter
      reflected from the topographic targets. To eliminate the effect of topographic
      scatter targets, a ratio detection technique was used. Wavelength modulation and
      harmonic detection were used to improve the detection sensitivity. The
      experimental detection limit is 50 ppmm, remote detection for a distance up to 20
      m away topographic scatter target is demonstrated. Using a known simulative leak
      pipe, minimum detectable pipe leak flux is less than 10 ml/min.

PMID- 16563856
TI  - Hepatocyte nuclear factor-4alpha and -1 small interfering RNA inhibits hepatocyte
      differentiation induced by extracellular matrix.
AB  - Liver-specific genes and hepatocyte nuclear factor (HNF)-4alpha and -1 are
      coordinately regulated by extracellular matrix (ECM). However, still are unclear
      interactions between liver-specific genes and these liver-enriched transcription
      factors in the mechanism of hepatocyte differentiation regulated by ECM. To
      elucidate the relationship, we used small interfering RNA (siRNA), which obtains
      strong and specific knockdown of gene expression in cell culture. Treatment with
      siHNF-4alpha and siHNF-1 declined the expression levels for HNF-4alpha mRNA and
      HNF-1 mRNA in primary rat hepatocytes, respectively. The mRNA expressions of
      albumin, transthyretin, and apolipoproteins that were up-regulated in hepatocytes
      cultured on a basement membrane matrix, Engelbreth-Holm-Swarm (EHS) gel, were
      decreased in the presence of siHNF-4alpha or siHNF-1. Moreover, siHNF-4alpha and
      siHNF-1 did not affect the morphology and actin assembly of hepatocytes. These
      findings demonstrated that HNF-4alpha and HNF-1 directly regulate liver-specific
      gene expression and might be downstream of cytoskeletal organization in the
      mechanism by which the differentiated phenotype of hepatocytes is regulated by
      EHS gel.

PMID- 16563855
TI  - Optical spectra of anionic boron cluster compounds and their utilization for
      photometric detection.
AB  - The article presents first collection of UV-vis absorption spectra of purely
      synthetic boron cluster compounds. Single-cage compounds have at least 11 cluster
      atoms; cobaltadicarboranes consists of 2 substituted 11-vertex bis(dicarbollide)
      clusters sandwiching the central cobalt atom. Spectrum of any of 18 investigated
      compounds has absorption maximum between 200 and 210 nm; its molar extinction
      coefficient is of the order of 10(3)-10(4)L/molcm. Second maximum exists in a
      spectrum of a single-cage compound if its exo-skeletal substituent absorbs UV
      light above 200 nm. Spectra of cobaltadicarbaboranes both bridged and unbridged
      have pronounced second maxima between 270 and 300 nm. Their molar extinction
      coefficients range from 10(4) to 10(5)L/molcm. First light absorption minimum is
      close to 254 nm in spectra with two and more absorption maxima. Several
      correlations are derived between structure of investigated compounds and their UV
      vis absorption spectra.

PMID- 16563857
TI  - Significance and fate of septal fibrosis of the liver.
AB  - Septal fibrosis commonly occurs during chronic diseases of the liver. It is
      experimentally reproduced in a proportion of rats treated with pig-serum, and in
      100% of rats infected with Capillaria hepatica. These models have only been used
      in relatively short-term studies. To contribute to the natural history and
      significance of hepatic septal fibrosis it is important to disclose its fate
      after prolonged observation, and following partial or total withdrawal of its
      inciting cause. Adult Wistar rats were sacrificed 3, 6, 9 and 12 months following
      inoculation of 800 embryonated eggs of C. hepatica. Besides routine histology,
      liver sections were submitted to immunohistochemical, immunofluorescence and
      ultrastructural techniques for the identification of cells and extracellular
      matrix components present in the fibrous septa. Septal blood vessels were studied
      after portal vein perfusion with India-ink, while the hepatic functional profile
      and levels of anti-C. hepatica antibodies were determined in collected sera.
      Results revealed that all parasites were already dead 2 months from inoculation,
      and the accumulated eggs in the liver lost their capacity to embryonate around
      the 4th-6th month, when progressive reduction in the number of cells and in the
      amount of collagen occurred in the septa. Septal fibrosis persisted throughout
      the time of experimentation (12 months). This fibrosis was seen as a supporting
      stroma for septal vessels that conducted portal blood directly to the sinusoids.
      Thus, persistence of fibrosis was probably related to its morphological and
      functional association with blood vessels.

PMID- 16563858
TI  - Natural polymorphism in protease and reverse transcriptase genes and in vitro
      antiretroviral drug susceptibilities of non-B HIV-1 strains from treatment-naive
      patients.
AB  - BACKGROUND: Most studies on antiretroviral (ARV) resistance of human
      immunodeficiency virus (HIV) have been done on subtype B which only represent a
      limited proportion of infections worldwide. OBJECTIVE: Understand baseline
      susceptibilities to ARVs in non-B strains. METHODS: To explore in greater detail
      possible intrinsic resistance to antiretroviral drugs in non-B subtypes,
      phenotypic resistance was tested in 35 non-B (A, D, F, G, J; CRF02, 06, 09, 11,
      13) HIV-1 isolates obtained from ARV treatment naive patients. The panel includes
      strains with an increasing number of minor mutations in the protease gene and/or
      with atypical mutations at positions associated with resistance in protease and
      RT. RESULTS: We detected phenotypic resistance (fold-change values equal or
      superior to biological test cut-offs (BCO) in 14 of the 35 strains, 4 strains had
      decreased in vitro susceptibility to more than one drug. However, it is important
      to note that in most cases the increased fold-changes were close to the BCOs.
      Phenotypic resistance was observed against each of the three ARV drug classes:
      ritonavir (n=3), nelfinavir (n=2), saquinavir (n=2), zidovudine (n=2), stavudine
      (n=1), didanosine (n=1); delavirdine (n=6), efavirenz (n=1) and nevirapine (n=1).
      Some mutations could be associated with decreased in vitro susceptibility: 1 of 3
      strains only with mutations M46I/L in protease, 1/2 A98S, K101N, V108I, V179I,
      and P236L in reverse transcriptase. Interestingly, the presence of an increasing
      number of minor mutations in the protease gene was not associated with decreased
      in vitro susceptibility to protease inhibitors. CONCLUSION: It is necessary to
      continue phenotypic studies on non-subtype B strains to identify the role of all
      polymorphisms present in protease and RT genes and to optimize interpretation
      algorithms. Data obtained from large, diverse populations of HIV-1 infected
      individuals is critical for defining and standardizing the quantification of
      resistance (phenotypic and genotypic testing).

PMID- 16563859
TI  - Non-compaction cardiomyopathy associated with myocardial bridging: A frequently
      overlooked or misdiagnosed cardiomyopathy.
AB  - Isolated ventricular non-compaction (IVNC) is an unclassified cardiomyopathy
      which occurs due to a morphogenetic abnormality involving an arrest of compaction
      of the loose myocardial meshwork during fetal ontogenesis. Despite recent
      advances in knowledge, diagnosis remains problematic because of its similarity to
      other diseases of the myocardium and endocardium. In this report, we describe a
      case of IVNC and myocardial bridging. The patient had been misdiagnosed with
      apical hypertrophic cardiomyopathy 2 years earlier. The correct diagnosis was
      established by transthoracic echocardiography and confirmed by cardiac
      catheterization and angiocardiography.

PMID- 16563860
TI  - A challenge to fitness testing in primary schools.
AB  - We challenge the tradition of fitness testing in schools on the basis of purpose,
      procedures and outcomes. A number of assumptions about validity of selected tests
      are raised. The need to be able to track fitness through childhood into adulthood
      is challenged with limited scientific evidence of longitudinal tracking.
      Supporters of wide-scale fitness testing of children in schools include
      researchers whose intention is to promote public health awareness and policy. But
      a variety of confounding factors can affect field-based testing and lower the
      confidence in intra and inter group comparisons. Confounders include variability
      in motivation, familiarisation, external conditions, group dynamics, self
      efficacy in testing, and perceived value of testing and likely outcomes. With
      acknowledged limitations, a more appropriate context for fitness testing for
      young people who have a strong commitment to physical activity may lie more in a
      professionally delivered sports-specific setting rather than in large-scale
      school-based testing. Given the less than desirable participation in activity
      outside of school and the distressing prevalence of childhood overweight and
      obesity, it is unlikely that fitness testing experiences will provide children
      with much needed positive encouragement for lifelong physical activity.
      Alternative strategies for school-based assessment of the promotion of child
      health through physical activity are proposed.

PMID- 16563861
TI  - Reducing the symptoms of lymphoedema: is there a role for aromatherapy?
AB  - Lymphoedema is a chronic and debilitating condition caused by lymphatic
      insufficiency, which may have serious physical, social and psychological
      implications for the patient. It is usually managed by a combination of
      strategies aimed at protecting and decongesting the oedematous limb(s) and
      stimulating the development of supplementary lymphatic pathways to control
      swelling in the long-term. However, it is not known which therapies are the most
      effective. Anecdotally, the addition of aromatherapy oils to massage cream may
      have a positive effect on symptom relief in people with cancer, although evidence
      is again lacking. This paper describes a randomized trial of self-massage and
      skin care using a cream containing aromatherapy oils versus self-massage and skin
      care using a cream without aromatherapy oils on objective limb volume
      measurements and symptom relief as measured by the Measure Yourself Medical
      Outcome Profile 2 (MYMOP2) in a sample of people with lymphoedema. Results
      indicate that self-massage and skin care significantly improved patient
      identified symptom relief and wellbeing for this sample. It also slightly, but
      not significantly reduced limb volume. However, aromatherapy oils, carefully
      chosen on the basis that they should benefit this group, did not appear to
      influence any improvement in these measures.

PMID- 16563862
TI  - Satellite cell self-renewal.
AB  - Regeneration of adult skeletal muscle involves the activation, proliferation and
      differentiation of satellite cells - quiescent tissue-specific stem cells
      occupying a specialised niche beneath the basal laminae of myofibres. Recent
      studies show that transplanted satellite cells both generate new muscle and
      undergo self-renewal. Data from cell culture experiments suggest that self
      renewal occurs through the return to quiescence of cycling progeny. Several
      molecules have been implicated in the regulation of satellite cell quiescence,
      activation and renewal, including the transcription factors Pax7, MyoD and Myf5,
      the cell-surface glycoprotein CD34, and the membrane lipid sphingomyelin.
      Evidence suggests that non-satellite cell types from muscle interstitium and bone
      marrow also give rise to myonuclei, although their contributions relative to the
      satellite cell remain to be established.

PMID- 16563863
TI  - Pulmonary and vascular pharmacology of sphingosine 1-phosphate.
AB  - Dysregulation of vasomotor tone, endothelial barrier function and immune cell
      trafficking are central to the pathology of many lung diseases, including acute
      lung injury, adult respiratory distress syndrome, chronic obstructive pulmonary
      disease and asthma. There is increasing evidence that the serum sphingolipid
      sphingosine 1-phosphate and its G-protein-coupled receptors are pivotal not only
      in the regulation of lymphocyte migration, but also in the maintenance of
      vascular homeostasis and the preservation of permeability barriers that separate
      discrete compartments in the lung.

PMID- 16563864
TI  - Human muscle stem cells.
AB  - Stem cells are unspecialized cells that have been defined in many different ways
      but they have two important characteristics that distinguish them from other
      cells in the body. First, they can replenish their numbers for long periods
      through cell division. Second, after receiving certain chemical signals, they can
      produce, through asymmetric cell division, a progeny that can differentiate or
      transform into specialized cells with specific functions, such as heart, nerve or
      muscle. In recent years, stem cells have received much attention owing to their
      potential use in cell-based therapies for human neurodegenerative diseases such
      as Parkinson's disease, stroke and muscular dystrophies. However, many questions
      need to be resolved before stem cells with myogenic potential are used in
      clinical standard protocols.

PMID- 16563865
TI  - Reprogramming of the tumour B-cell phenotype in Hodgkin lymphoma.
AB  - Hodgkin and Reed-Sternberg (HRS) cells, the tumour cells in classical Hodgkin
      lymphoma, derive from mature B cells but have largely lost their B-cell
      phenotype. This extensive reprogramming is unique among B-cell lymphomas. A
      recent study by Dorken and colleagues provides an interesting insight into the
      mechanisms for this reprogramming by demonstrating that the key B-cell
      determining transcription factor E2A is inhibited in HRS cells by the deregulated
      expression of its inhibitors activated B-cell factor (ABF)-1 and inhibitor of
      differentiation and DNA binding (Id)2.

PMID- 16563866
TI  - Human and livestock migrations: a history of bot fly biodiversity in the
      Mediterranean region.
AB  - The bot fly (oestrid) is responsible for myiasis in domestic animals. The
      presence in some regions of southern Europe of an unusually large number of
      different species of bot fly suggests a high degree of oestrid biodiversity in
      this area. The many factors that can influence parasitic species composition
      (e.g. host and parasite genetics, relationships with their hosts and environment,
      and animal management) include the movement of domestic animals in association
      with migrating human populations in southern Europe over thousands of years. From
      its geographical position, which was strategically important in controlling
      commercial trade routes in early Western civilization, the Mediterranean sea has
      for more than 3000 years constituted the hub of many different cultures,
      populations, genes and agricultural practices. The movement of animals and their
      associated parasites in this region can help to explain the evolution of
      parasitic biodiversity.

PMID- 16563867
TI  - Towards subtlety: understanding the role of Toll-like receptor signaling in
      susceptibility to human infections.
AB  - Recent years have seen a dramatic improvement in our understanding of the role of
      innate immunity, and particularly Toll-like receptor (TLR) signaling, in human
      host defense. Appreciation of how defects in human TLR signaling enhance
      susceptibility to infection began with the identification of patients with
      monogenic immunodeficiencies, such as hypohydrotic ectodermal dysplasia with
      immunodeficiency and IRAK4 deficiency. Empowered by technological advances in
      genotyping and bioinformatics, we are now beginning to appreciate how common
      genetic variation in the genes controlling the innate immune response alters
      infectious susceptibility in a subtle but specific fashion. This review
      highlights the mechanisms of infectious susceptibility that result from complex
      interactions between the genetically variable host and microbe and explores how
      this new knowledge may ultimately translate into better care for our patients.

PMID- 16563869
TI  - Cervical cancer in the developing world.
AB  - In developed countries, systematic screening programmes have reduced the
      morbidity and mortality resulting from cervical cancer. Cytological methods of
      screening have been the mainstay in these countries. Nevertheless, there is scant
      evidence that cytology-based screening has had any effect in reducing cervical
      cancer mortality in less-developed countries. In fact, the challenge in less
      developed countries is surpassed by the complex array of problems that go far
      beyond the introduction of simplified technologies. Currently, there are two main
      issues on this subject: the assessment of simpler screening methods, and the
      evaluation of different strategies regarding which women to target and the
      screening interval. Achieving high rates of coverage and compliance of the target
      population through high-quality procedures has remained the most difficult goal
      to achieve. Nevertheless, it is believed that creativity, flexibility and well
      focused use of resources can reduce the inequitable burden of cervical cancer
      borne by women in poor countries.

PMID- 16563868
TI  - Adenomyosis: epidemiological factors.
AB  - Epidemiological studies of adenomyosis are difficult to interpret because the
      diagnostic criteria vary so widely that the disease may be easily over-diagnosed.
      This would severely hamper any attempt to define incidence and prevalence of the
      condition and the related risk factors, and would limit the possibility of
      clarifying to what extent adenomyosis contributes to clinical symptoms. There is
      a need for stringent and widely accepted diagnostic criteria in order to define
      not only the presence of adenomyosis but also depth of penetration and degree of
      spread of foci. Moreover, the evidence available on epidemiological
      characteristics of women with adenomyosis is greatly biased by the type of
      population studied, i.e. women undergoing hysterectomy. Therefore, a consensus on
      non-surgical diagnostic criteria at transvaginal ultrasonography and MRI is
      indispensable and urgently needed in order to be able to conduct epidemiological
      studies in women younger than those evaluated until now.

PMID- 16563871
TI  - Access to safe abortion within the limits of the law.
AB  - The World Health Organization defines unsafe abortion as a procedure for
      terminating an unintended pregnancy carried out by people lacking the necessary
      skills or in an environment that does not conform to minimal medical standards,
      or both. The Programme of Action of the International Conference on Population
      and Development recommends that 'In circumstances where abortion is not against
      the law, such abortion should be safe'. However, millions of women still risk
      their lives by undergoing unsafe abortion even if they comply with the law. This
      is a serious violation of women's human rights, and obstetricians and
      gynaecologists have a fundamental role in breaking the administrative and
      procedural barriers to safe abortion. This chapter reviews the magnitude of the
      problem, its consequences for women's health, the barriers to access to safe
      abortion, including its legal status, the effect of the law on the rate and the
      consequences of abortion, the human rights implications and the current evidence
      on methods to perform safe abortion. This chapter concludes with an analysis of
      what can be done to change the current situation.

PMID- 16563870
TI  - Pathology and physiopathology of adenomyosis.
AB  - Adenomyosis is defined by the presence of endometrial mucosa within the
      myometrium. This probably occurs by invagination of the basalis endometrium into
      the myometrium. The process of invagination and intramyometrial spreading may be
      facilitated by the non-cyclic, anti-apoptotic activity of the basalis associated
      with relative hyper-oestrogenic states. Most cases of adenomyosis are discovered
      in multiparous women during the 'transitional' years (40-50 years), and the
      condition is associated with menorrhagia, dysmenorrhoea, endometrial polyps and
      leiomyomata uteri. Endometrioid adenocarcinoma is often associated with
      adenomyosis, is frequently of early stage and low histological grade, is hormone
      sensitive, and has an excellent prognosis. Extension of malignant growth into
      foci of adenomyosis has no adverse effect on prognosis. Definite diagnosis and
      treatment of adenomyosis are obtained by hysterectomy. Although adenomyotic
      endometrial glands are hormone-sensitive, exogenous progestogenic agents are
      ineffective for the treatment of adenomyosis. Anti-oestrogenic danazol and
      gonadotrophin-releasing hormone (GnRH) analogues induce suppression of
      adenomyosis, but their use must be of short duration. Surgical extirpation,
      therefore, is the best therapeutic option.

PMID- 16563872
TI  - Medical and surgical management of adenomyosis.
AB  - Adenomyosis of the uterus is a common condition amongst women in their
      reproductive years. It is defined as the presence of heterotopic endometrial
      glands and stroma in the myometrium with adjacent smooth muscle hyperplasia. The
      common presenting symptoms are painful and heavy periods and infertility,
      although many women are asymptomatic. Adenomyosis is thought to affect 1% of
      women and is typically diagnosed in the 4th and 5th decades of life. The
      aetiology is unclear, and until recently a diagnosis was made only after invasive
      and destructive surgery. With the advent of improved imaging of the pelvic
      organs, and in particular magnetic resonance imaging, the diagnosis of
      adenomyosis is being made more frequently. Unfortunately, because the disease has
      been infrequently diagnosed prior to hysterectomy, there are few well-designed
      studies of medical or surgical management. Management with hormonal treatment
      that aims to reduce the proliferation of endometrial cells is promising, but
      there is a paucity of well-designed studies to guide treatment. Hysterectomy or
      use of the levonorgestrel intrauterine system (LNG-IUS) remains the mainstay of
      treatment.

PMID- 16563873
TI  - What is the relevance of women's sexual and reproductive rights to the practising
      obstetrician/gynaecologist?
AB  - Women's sexual and reproductive rights are an integral part of daily practice for
      obstetricians/gynaecologists and the key to the survival and health of women
      around the world. Women's sexual and reproductive health is often compromised
      because of infringements of their basic human rights, not the lack of medical
      knowledge. Understanding the relevance of respecting and promoting sexual and
      reproductive rights is critical for providing current standards of care, and
      includes access to information and care, confidentiality, informed consent and
      evidence-based practice. The violation of women's rights in their daily lives
      through common problems such as gender-based violence and discrimination results
      in serious consequences for their health. Obstetricians/gynaecologists are
      natural advocates for women's health, yet may be lacking in their understanding
      of relevant laws or the limits of conscientious objection. This chapter outlines
      the framework for sexual and reproductive rights, and explores its relevance to
      the practising clinician.

PMID- 16563875
TI  - Hormonal control of C. elegans dauer formation and life span by a Rieske-like
      oxygenase.
AB  - C. elegans diapause, gonadal outgrowth, and life span are regulated by a
      lipophilic hormone, which serves as a ligand to the nuclear hormone receptor DAF
      12. A key step in hormone production is catalyzed by the CYP450 DAF-9, but the
      extent of the biosynthetic pathway is unknown. Here, we identify a conserved
      Rieske-like oxygenase, DAF-36, as a component in hormone metabolism. Mutants
      display larval developmental and adult aging phenotypes, as well as patterns of
      epistasis similar to that of daf-9. Larval phenotypes are potently reversed by
      crude lipid extracts, 7-dehydrocholesterol, and a recently identified DAF-12
      sterol ligand, suggesting that DAF-36 works early in the hormone biosynthetic
      pathway. DAF-36 is expressed primarily within the intestine, a major organ of
      metabolic and endocrine control, distinct from DAF-9. These results imply that C.
      elegans hormone production has multiple steps and is distributed, and that it may
      provide one way that tissues register their current physiological state during
      organismal commitments.

PMID- 16563874
TI  - C-terminal-truncated microdystrophin recruits dystrobrevin and syntrophin to the
      dystrophin-associated glycoprotein complex and reduces muscular dystrophy in
      symptomatic utrophin/dystrophin double-knockout mice.
AB  - C-terminal-truncated (DeltaC) microdystrophin is being developed for Duchenne
      muscular dystrophy gene therapy. Encouraging results have been achieved in the
      mdx mouse model. Unfortunately, mdx mice do not display the same phenotype as
      human patients. Evaluating DeltaC microdystrophin in a symptomatic model will be
      of significant relevance to human trials. Utrophin/dystrophin double-knockout (u
      dko) mice were developed to model severe dystrophic changes in human patients. In
      this study we evaluated the therapeutic effect of the DeltaR4-R23/DeltaC
      microdystrophin gene (DeltaR4/DeltaC) after serotype-6 adeno-associated virus
      mediated gene transfer in neonatal u-dko muscle. At 2 months after gene transfer,
      the percentage of centrally nucleated myofiber was reduced from 89.2 to 3.4% and
      muscle weight was normalized. Furthermore, we have demonstrated for the first
      time that DeltaC microdystrophin can eliminate interstitial fibrosis and
      macrophage infiltration and restore dystrobrevin and syntrophin to the dystrophin
      associated glycoprotein complex. Interestingly neuronal nitric oxide synthase was
      not restored. The most impressive results were achieved in muscle force
      measurement. Neonatal gene therapy increased twitch- and tetanic-specific force.
      It also brought the response to eccentric contraction-induced injury to the
      normal range. In summary, our results suggest that the DeltaR4/DeltaC microgene
      holds great promise in preventing muscular dystrophy.

PMID- 16563876
TI  - Fine-tuning modulation of myenteric motoneurons by endogenous adenosine: on the
      role of secreted adenosine deaminase.
AB  - Besides the well-characterized inhibitory effect of adenosine in the
      gastrointestinal tract mediated by A1 receptors, we recently demonstrated that
      endogenously generated adenosine facilitates [3H]acetylcholine release from
      myenteric neurons through preferential activation of prejunctional A2A receptors.
      The co-existence of both receptor subtypes on cholinergic neurons prompted the
      question of how does adenosine discriminate between these receptors to regulate
      synaptic transmission in the longitudinal muscle-myenteric plexus (LM-MP) of the
      rat ileum. Electrical stimulation of the LM-MP increased the outflow of
      adenosine, inosine and hypoxanthine. Myenteric neurons seem to be the main source
      of endogenous adenosine, since blockade of action potentials with tetrodotoxin (1
      microM) or omission of Ca2+ (plus EGTA, 1 mM) in the buffer essentially abolished
      nucleosides release, while adenosine outflow remained unchanged when smooth
      muscle contractions were prevented by nifedipine (1 microM). Inhibition of ecto
      5'-nucleotidase by concanavalin A (0.1 mg ml-1) produced only a moderate decrease
      (approximately 25%) on adenosine accumulation in the LM-MP, indicating that the
      extracellular catabolism of released ATP might not be a major source of the
      nucleoside. Data using the acetylcholinesterase inhibitor, physiostigmine (10
      microM), and several subtype-specific muscarinic receptor antagonists, 4-DAMP
      (100 nM), AF-DX 116 (10 microM) and muscarinic toxin-7 (1 nM), suggest that
      cholinergic motoneurons are endowed with muscarinic M3 autoreceptors facilitating
      the outflow of adenosine. Surprisingly, bath samples collected after stimulating
      the LM-MP exhibited a relatively high adenosine deaminase (ADA) activity (0.60+/
      0.07 U ml-1), which increased in parallel with the accumulation of adenosine and
      its deamination products. Our findings are in keeping with the hypothesis that
      ADA secretion, along with a less-efficient dipyridamole-sensitive nucleoside
      transport system, may restrict endogenous adenosine actions to the synaptic
      region channelling to facilitatory A2A receptors activation. Such a local
      environment may also limit diffusion of exogenously added adenosine towards the
      active zones, as we showed that this constrain may be overcome by inhibiting ADA
      activity with erythro-9(2-hydroxy-3-nonyl) adenine (50 microM).

PMID- 16563877
TI  - Role of HLA-B51 and HLA-B52 in susceptibility to pulmonary tuberculosis.
AB  - MHC class I-restricted CD8+ T cells are important for the generation of
      protective immune responses in MTB infection. CD8+ CTL (cytotoxic T-lymphocyte)
      derived IFN-g may be especially important both for cells lacking MHC class II
      molecules, e.g. in the lung and for macrophages where mycobacteria can evade
      recognition during chronic infection by sequestering their antigens away from
      sensitized CD4+ T cells. This study was designed to detect any association of MHC
      class I (HLA-B) molecules with pulmonary tuberculosis. A total of 75 individuals,
      comprising of 33 patients with pulmonary tuberculosis; 12 HIV patients who
      developed tuberculosis and 30 healthy controls, were included in the study. They
      were typed for HLA-B by the PCR-SSP method. The results of only HLA-B alleles,
      which are highly significant, are presented here. The number of healthy
      individuals with HLA-B52 was significantly high when compared to the patient
      groups (healthy versus TB: 21.2% versus 0.0%, OR=0.0, P<0.0001, P(c)=0.003;
      healthy versus HIV-TB: 21.2% versus 16.7%; OR=0.74; P<0.001; P(c)=0.003). In
      contrast, the number of patients, both TB- and HIV-TB-positive, with HLA-B51 was
      significantly high when compared to the healthy group of individuals (TB versus
      healthy: 36.7% versus 3%; OR=18.53; P<0.0001; P(c)=0.001; HIV-TB versus healthy:
      41.7% versus 3%; OR=22.86; P<0.0001; P(c)=0.001). Only one healthy control was
      positive to HLA-B51; however this individual also had HLA-B52. The results of
      this study suggest that HLA-B52(5) has a negative, i.e. a protective association
      and HLA-B51(5) has a positive (susceptible) association, for pulmonary
      tuberculosis. Studies on HLA-B51 and HLA-B52 in a larger population to assess
      their role in tuberculosis may be useful for TB-vaccination strategies, since HLA
      profiles are likely to be related to vaccine efficacy.

PMID- 16563878
TI  - Preparation of biosensors by immobilization of polyphenol oxidase in conducting
      copolymers and their use in determination of phenolic compounds in red wine.
AB  - Electrochemically produced graft copolymers of thiophene capped
      polytetrahydofuran (TPTHF1 and TPTHF2) and pyrrole were achieved by constant
      potential electrolysis using sodium dodecylsulfate (SDS) as the supporting
      electrolyte. Characterizations were based on Fourier transform infrared
      spectroscopy (FTIR) and scanning electron microscopy (SEM). Electrical
      conductivities were measured by the four-probe technique. Novel biosensors for
      phenolic compounds were constructed by immobilizing polyphenol oxidase (PPO) into
      conducting copolymers prepared by electropolymerization of pyrrole with thiophene
      capped polytetrahydrofuran. Kinetic parameters, maximum reaction rate (V(max))
      and Michaelis-Menten constant (K(m)) and optimum conditions regarding temperature
      and pH were determined for the immobilized enzyme. Operational stability and
      shelf-life of the enzyme electrodes were investigated. Enzyme electrodes of
      polyphenol oxidase were used to determine the amount of phenolic compounds in two
      brands of Turkish red wines and found very useful owing to their high kinetic
      parameters and wide pH working range.

PMID- 16563879
TI  - Electroreduction of dioxygen on Aunano-DNA film electrode in acidic electrolyte.
AB  - The colloidal Au nanoparticles-deoxyribonucleic acid (Au(nano)-DNA) film modified
      glassy carbon electrode (GCE) has been fabricated and the electrochemical
      reduction of dioxygen (O(2)) at this modified GCE has been studied in 0.2 mol/L
      air-saturated acetate buffer (pH=5.2) using cyclic voltammetry (CV),
      chronocoulometry (CC), linear scan voltammetry (LSV) and rotating disk electrode
      (RDE) as diagnostic techniques. The modified electrode shows excellent
      enhancement effect towards the reduction of dioxygen to hydrogen peroxide
      (H(2)O(2)), and the overpotential is lower than that at bare GCE. A well-defined
      dioxygen reduction peak appeared at about -0.24 V. Based on experimental results,
      a reaction mechanism is proposed and discussed.

PMID- 16563881
TI  - Flying high: a theoretical analysis of the factors limiting exercise performance
      in birds at altitude.
AB  - The ability of some bird species to fly at extreme altitude has fascinated
      comparative respiratory physiologists for decades, yet there is still no
      consensus about what adaptations enable high altitude flight. Using a theoretical
      model of O(2) transport, we performed a sensitivity analysis of the factors that
      might limit exercise performance in birds. We found that the influence of
      individual physiological traits on oxygen consumption (Vo2) during exercise
      differed between sea level, moderate altitude, and extreme altitude. At extreme
      altitude, haemoglobin (Hb) O(2) affinity, total ventilation, and tissue diffusion
      capacity for O(2) (D(To2)) had the greatest influences on Vo2; increasing these
      variables should therefore have the greatest adaptive benefit for high altitude
      flight. There was a beneficial interaction between D(To2) and the P(50) of Hb,
      such that increasing D(To2) had a greater influence on Vo2 when P(50) was low.
      Increases in the temperature effect on P(50) could also be beneficial for high
      flying birds, provided that cold inspired air at extreme altitude causes a
      substantial difference in temperature between blood in the lungs and in the
      tissues. Changes in lung diffusion capacity for O(2), cardiac output, blood Hb
      concentration, the Bohr coefficient, or the Hill coefficient likely have less
      adaptive significance at high altitude. Our sensitivity analysis provides
      theoretical suggestions of the adaptations most likely to promote high altitude
      flight in birds and provides direction for future in vivo studies.

PMID- 16563882
TI  - Further examination of alveolar septal adaptation to left pneumonectomy in the
      adult lung.
AB  - Recent data from our laboratory are presented concerning alveolar septal
      adaptation following 42-45% lung resection by left pneumonectomy (PNX) in adult
      foxhounds compared to sham-operated control animals. Results confirm our previous
      conclusion that compensation in the remaining lung occurs without a net growth of
      additional alveolar septal tissue. The major ultrastructural responses are (a)
      alveolar capillary distention, which recruits capillary blood volume and surface
      area, leading to a 30-50% increase in lung diffusing capacity estimated by
      morphometry, a magnitude similar to that measured by physiologic methods; (b) a
      selectively increased volume of type 2 alveolar epithelial cells. These data,
      taken together with the balanced compensatory growth of alveolar septal cells
      observed in adult dogs following 55-58% lung resection by right PNX, support a
      graded alveolar cellular response to chronic mechanical strain with the alveolar
      epithelial cells being activated first; as strain increases further with greater
      lung resection other alveolar cells also become activated leading to an overt
      increase in septal tissue volume. The spatial distribution of lobar mechanical
      strain and lobar tissue volume assessed by high resolution computed tomography
      was markedly non-uniform after PNX, suggesting possible non-uniform distribution
      of alveolar cellular response. The sequential activation of physiologic
      recruitment and cellular adaptation confer additive functional benefits that
      optimize long-term exercise performance after PNX.

PMID- 16563883
TI  - Quantitative determination of MCC-555, a novel insulin sensitizer in beagle dog
      plasma by high-performance liquid chromatography with fluorescence detection.
AB  - A sensitive high-performance liquid chromatographic method with fluorescence
      detection has been developed for determination of MCC-555 (5-[[6-(2-fluorbenzyl)
      oxy-2-naphy] methyl]-2,4-thiazolidinedione) in beagle dog plasma. Sample
      preparation was done by protein precipitation with acetonitrile and a synthetic
      intermediate of MCC-555 (5-[[6-(2-fluorbenzyl)-oxy-2-naphy] methylene]-2,4
      thiazolidinedione) was used as the internal standard (IS). The isocratic mobile
      phase consisted of acetonitrile-10 mmol/l sodium phosphate buffer (pH 4.5)
      (65:35, v/v) was delivered at a flow rate of 1 ml/min to a Kromasil C(18)
      reversed-phase column (250 mm x 4.6 mm, 5 microm). The compounds were detected by
      fluorescence detection, using an excitation wavelength of 232 nm, and emission
      wavelength of 352 nm. Calibration curves of MCC-555 were linear in the
      concentration range of 0.005-2.0 microg/ml. Intra- and inter-day precision ranged
      from 3.4 to 5.4% and 3.0 to 8.8%, respectively. No endogenous interferences were
      observed with either MCC-555 or IS. The assay is simple, economical, precise, and
      is directly applicable to pharmacokinetic studies in beagle dogs involving three
      dose administrations.

PMID- 16563884
TI  - Automated solid-phase extraction method for measuring urinary polycyclic aromatic
      hydrocarbon metabolites in human biomonitoring using isotope-dilution gas
      chromatography high-resolution mass spectrometry.
AB  - In order to perform comprehensive epidemiological studies where multiple
      metabolites of several PAHs are measured and compared in low-dose urine samples,
      fast and robust methods are needed to measure many analytes in the same sample.
      We have modified a previous method used for measuring polycyclic aromatic
      hydrocarbon (PAH) metabolites by automating the solid-phase extraction (SPE) and
      including an additional eight metabolites. We also added seven new carbon-13
      labeled standards, which improves the use of isotope-dilution calibration. Our
      method included enzyme hydrolysis, automated SPE and derivatization with a
      silylating reagent followed by gas chromatography (GC), coupled with high
      resolution mass spectrometry (HRMS). Using this method, we measured 23
      metabolites, representing 9 parent PAHs, with detection limits in the low pg/mL
      range. All steps in the clean-up procedure were optimized individually, resulting
      in a method that gives good recoveries (69-93%), reproducibility (coefficient of
      variation for two quality control pools ranged between 4.6 and 17.1%, N>156), and
      the necessary specificity. We used the method to analyze nearly 3000 urine
      samples in the fifth National Health and Nutrition Examination Survey (NHANES
      2001-2002).

PMID- 16563885
TI  - Direct and simultaneous analysis of loxoprofen and its diastereometric alcohol
      metabolites in human serum by on-line column switching liquid chromatography and
      its application to a pharmacokinetic study.
AB  - A simple, rapid, and accurate column-switching liquid chromatography method was
      developed and validated for direct and simultaneous analysis of loxoprofen and
      its metabolites (trans- and cis-alcohol metabolites) in human serum. After direct
      serum injection into the system, deproteinization and trace enrichment occurred
      on a Shim-pack MAYI-ODS pretreatment column (10 mm x 4.6 mm i.d.) by an eluent
      consisting of 20 mM phosphate buffer (pH 6.9)/acetonitrile (95/5, v/v) and 0.1%
      formic acid. The drug trapped by the pretreatment column was introduced to the
      Shim-pack VP-ODS analytical column (150 mm x 4.6 mm i.d.) using
      acetonitrile/water (45/55, v/v) containing 0.1% formic acid when the 6-port valve
      status was switched. Ketoprofen was used as the internal standard. The analysis
      was monitored on a UV detector at 225 nm. The chromatograms showed good
      resolution, sensitivity, and no interference by human serum. Coefficients of
      variations (CV%) and recoveries for loxoprofen and its metabolites were below 15
      and over 95%, respectively, in the concentration range of 0.1-20 microg/ml. With
      UV detection, the limit of quantitation was 0.1 microg/ml, and good linearity (r
      = 0.999) was observed for all the compounds with 50 microl serum samples. The
      mean absolute recoveries of loxoprofen, trans- and cis-alcohol for human serum
      were 89.6 +/- 3.9, 93.5 +/- 3.2, and 93.7 +/- 4.3%, respectively. Stability
      studies showed that loxoprofen and its metabolites in human serum were stable
      during storage and the assay procedure. This analytical method showed excellent
      sensitivity with small sample volume (50 microl), good precision, accuracy, and
      speed (total analytical time 18 min), without any loss in chromatographic
      efficiency. This method was successfully applied to the pharmacokinetic study of
      loxoprofen in human volunteers following a single oral administration of
      loxoprofen sodium (60 mg, anhydrate) tablet.

PMID- 16563886
TI  - Rapid determination of solanesol in tobacco by high-performance liquid
      chromatography with evaporative light scattering detection following microwave
      assisted extraction.
AB  - Solanesol is the starting material for many high-value biochemicals, including
      coenzyme Q(10) and Vitamin-K analogues. The aim of the current study was to
      develop a reliable and fast analytical procedure for the determination of
      solanesol in tobacco using high-performance liquid chromatography (HPLC) with
      evaporative light scattering detection (ELSD) coupled with microwave-assisted
      extraction (MAE) as an efficient sample preparation technique. The HPLC
      conditions were Agilent C18 column using acetonitrile-isopropanol (60:40, v/v) as
      mobile phase at a flow rate of 1 ml/min. ELSD conditions were optimized at
      nebulizer-gas flow rate of 1.5 l/min and drift tube temperature of 65 degrees C.
      The method was validated to achieve the satisfactory precision and recovery, and
      the calibration range was 0.1-1.5 mg/ml. The developed analytical procedure was
      successfully applied to determine solanesol content in tobacco samples from
      different growing regions in China.

PMID- 16563887
TI  - Optimization and validation of a high-performance liquid chromatographic method
      with UV detection for the determination of ketoconazole in canine plasma.
AB  - An isocratic high-performance liquid chromatographic method with detection at 240
      nm was developed, optimized and validated for the determination of ketoconazole
      in canine plasma. 9-Acetylanthracene was used as internal standard. A Hypersil
      BDS RP-C18 column (250 mm x 4.6 mm, 5 microm particle size), was equilibrated
      with a mobile phase composed of methanol, water and diethylamine 74:26:0.1
      (v/v/v). Its flow rate was 1 ml/min. The elution time for ketoconazole and 9
      acetylanthracene was approximately 9 and 8 min, respectively. Calibration curves
      of ketoconazole in plasma were linear in the concentration range of 0.015-10
      microg/ml. Limits of detection and quantification in plasma were 5 and 15 ng/ml,
      respectively. Recovery was greater than 95%. Intra- and inter-day relative
      standard deviation for ketoconazole in plasma was less than 3.1 and 4.7%,
      respectively. This method was applied to the determination of ketoconazole plasma
      levels after administration of a commercially available tablet to dogs.

PMID- 16563888
TI  - Clinical expression of co-inherited Dubin-Johnson and thalassaemic heterozygous
      states.
AB  - Dubin-Johnson syndrome is a worldwide prevalent familial conjugated
      hyperbilirubinaemia. The identification of multidrug resistance-associated
      protein 2 provided an understanding of the complex metabolic impairment involved
      in this syndrome. We report the first family with modified clinical expression of
      Dubin-Johnson heterozygous state due to genotypic interaction with co-inherited
      beta and deltabeta thalassaemia, an interaction that has never been described.

PMID- 16563889
TI  - Effect of intentional infliximab use throughout pregnancy in inducing and
      maintaining remission in Crohn's disease.

PMID- 16563890
TI  - Fracture risk reduction during treatment with teriparatide is independent of
      pretreatment bone turnover.
AB  - INTRODUCTION: Teriparatide is a bone formation agent that increases bone turnover
      and mass, resulting in an increase in bone strength and a decrease in fracture
      risk. METHODS: The primary purpose of this analysis was to evaluate the
      association between pretreatment bone turnover marker (BTM) concentrations and
      the absolute and relative fracture risks after adjusting for baseline femoral
      neck BMD, number of prevalent vertebral fractures, and age. Because femoral neck
      BMD is commonly attained in the assessment of patients at risk for osteoporosis,
      we examined the ability of a multivariate assessment including pretreatment BTM
      concentration and femoral neck BMD to predict future fracture risk after
      adjusting for the number of prevalent vertebral fractures. We examined data from
      the Fracture Prevention Trial, a study designed to determine the effect of
      teriparatide 20 mcg/day and teriparatide 40 mcg/day on vertebral and nonvertebral
      fracture risk in postmenopausal women with osteoporosis. BTM were analyzed in two
      subsets of women within the Fracture Prevention Trial, and included serum bone
      specific alkaline phosphatase (BSAP), serum carboxy-terminal extension peptide of
      procollagen type I (PICP), serum amino-terminal extension peptide of procollagen
      type I (PINP), urinary free deoxypyridinoline (DPD), and urinary N-terminal
      telopeptide (NTX). RESULTS: Teriparatide significantly reduced the risk of
      fracture [four BTM subset (n = 520), placebo = 14.3%, teriparatide = 5.8%, P <
      0.05; PINP subset (n = 771), placebo = 17.7%, teriparatide = 5.5%, P < 0.05].
      Subjects with the highest pretreatment BTM concentrations had the greatest
      fracture risk. Teriparatide-mediated absolute risk reduction was greatest for
      women with high pretreatment bone turnover; however, the relative fracture risk
      reduction was independent of pretreatment bone turnover. After adjusting for
      pretreatment BTM and number of prevalent vertebral fractures, baseline femoral
      neck BMD was not a significant predictor of fracture risk. CONCLUSION:
      Teriparatide-mediated relative fracture risk reduction was independent of
      pretreatment bone turnover, demonstrating that this therapy offers clinical
      benefit to patients across a range of disease severity.

PMID- 16563891
TI  - Does low-density lipoprotein size add to atherogenic particle number in
      predicting the risk of fatal myocardial infarction?
AB  - The lipoprotein-related risk of coronary artery disease is determined principally
      by the balance between atherogenic lipoprotein particles, i.e., the lipoprotein
      that contain apolipoprotein-B (apo-B), and the antiatherogenic particles, i.e.,
      high-density lipoprotein particles that contain apo-A-I. However, there is also
      considerable evidence that patients with predominantly small dense low-density
      lipoprotein (LDL) have more adverse clinical outcomes than do those with large
      buoyant LDL. The AMORIS study prospectively examined the relative importance of
      lipoprotein lipids versus apolipoproteins on the risk of fatal myocardial
      infarction in a large Swedish cohort. This updated analysis includes 69,029 men
      and 57,167 women who were followed for a mean of 10.3 years. Our objective was to
      determine whether LDL size as reflected by the LDL cholesterol/apo-B ratio added
      significant predictive power to apo-B or the apo-B/apo-A-I ratio. Although apo-A
      I added significantly to the predictive power of apo-B, categorical and
      continuous multivariate analyses showed that this is not the case for LDL size.
      The strongest single lipoprotein-related risk factor was the apo-B/apo-A-I ratio.
      In conclusion, these results provide further confirmation of the importance of
      determining apo-B and apo-A-I in routine clinical practice.

PMID- 16563892
TI  - Frequency of recurrent ST-elevation myocardial infarction after fibrinolytic
      therapy in a different territory as a manifestation of multiple unstable coronary
      arterial plaques.
AB  - Multiple unstable plaques have been demonstrated by various imaging techniques in
      culprit and nonculprit arteries in patients with acute coronary syndromes, but
      the frequency with which clinical manifestations of multiple unstable plaques
      occur is unclear. To estimate this frequency in patients who present within 6
      hours with ST-elevation myocardial infarction, we studied electrocardiograms and
      cardiac marker levels of 722 patients with suspected reinfarction in the HERO-2
      trial of 17,073 patients; this trial compared intravenous bivalirudin with
      unfractionated heparin before administration of streptokinase. Twenty-six
      patients (3.6%) developed recurrent ST elevation in a different territory. Of all
      the patients who developed ST elevation in a different territory, 50% (13 of 26)
      did so during the 48 hours of randomized antithrombin therapy compared with 29%
      (140 of 487) of those who developed recurrent ST elevation in the index territory
      (p = 0.046). Recurrent index territory ST elevation occurred in 392 of 552
      patients (71%) with confirmed reinfarction, and ST elevation in a new territory
      occurred in 21 patients (3.8%) with confirmed reinfarction (2.3% and 0.12% of all
      HERO-2 enrollees, respectively). These data suggest that clinical manifestation
      of multiple unstable plaques of recurrent ST elevation and reinfarction in a
      territory different from that of the index ST elevation myocardial infarction
      after intravenous fibrinolytic and antithrombin therapies is rare.

PMID- 16563893
TI  - Return to full normal activities including work at two weeks after acute
      myocardial infarction.
AB  - Patients are generally advised to return to full normal activities, including
      work, 6 to 8 weeks after acute myocardial infarction (AMI). We assessed the
      outcomes of early return to normal activities, including work at 2 weeks, after
      AMI in patients who were stratified to be at a low risk for future cardiac
      events. Patients were considered for randomization before discharge if they had
      no angina, had left ventricular ejection fraction >40%, a negative result from a
      symptom-limited exercise stress test for ischemia (<2 mm ST depression) at 1
      week, and achieved >7 METs. Patients with left ventricular ejection fraction <40%
      were included only if they did not have inducible ventricular tachycardia at
      electrophysiologic studies. Seventy-two patients were randomized to return to
      normal activities at 2 weeks and 70 patients to undergo standard cardiac
      rehabilitation and return to normal activities at 6 weeks after AMI. There were
      no deaths or heart failure in either group. There was no significant difference
      in the incidence of reinfarction, revascularization, left ventricular function,
      lipids, body mass index, smoking, or exercise test results at 6 months. In
      conclusion, return to full normal activities, including work at 2 weeks, after
      AMI appears to be safe in patients who are stratified to a low-risk group. This
      should have significant medical and socioeconomic implications.

PMID- 16563894
TI  - Left ventricular geometry and survival in patients with normal left ventricular
      ejection fraction.
AB  - In hypertensive populations, left ventricular (LV) geometry, which is
      characterized by hypertrophy, predicts cardiovascular outcome. The left ventricle
      can also alter its shape by concentric remodeling (CR) in the absence of LV
      hypertrophy, a feature that is detected by echocardiography. This study assessed
      the prevalence and prognostic significance of various forms of LV geometry and
      changes in LV geometry over time in patients with normal LV systolic function.
      Retrospective analysis of a large clinical population (n = 35,602) that was
      referred for echocardiography was done, with all-cause mortality as the primary
      outcome. Abnormal LV geometry was identified in 46% of patients, with CR present
      in 35% (n = 12,362) and LV hypertrophy in 11% (n = 3,958). Patients with abnormal
      LV geometry were older and more obese compared with subjects with normal LV
      geometry. There was a strong relation between abnormal LV geometry and mortality,
      and patients with CR and LV hypertrophy exhibited considerably higher relative
      risk for all-cause mortality compared with subjects with normal LV geometry
      (relative risk [RR] 1.99, 95% confidence interval [CI] 1.88 to 2.18, p <0.0001;
      RR 2.13, 95% CI 1.89 to 2.40, p <0.0001, respectively). Subjects with CR who
      reverted to a normal geometric pattern had improved survival (RR 0.64, 95% CI
      0.42 to 0.97, p = 0.03) compared with those who progressed to LV hypertrophy (RR
      1.54, 95% CI 1.01 to 2.47, p = 0.05). In conclusion, CR, a form of cardiac
      adaptation, is frequently noted in patients with normal LV ejection fractions and
      confers a risk of death similar to that of LV hypertrophy. Normalization of CR is
      associated with better survival, whereas transition to LV hypertrophy increases
      mortality.

PMID- 16563895
TI  - Association of the metabolic syndrome with early coronary disease in families
      with frequent myocardial infarction.
AB  - This study examined the extent to which the metabolic syndrome (MS) augments the
      risk for major cardiovascular events in healthy patients with a strong genetic
      background for coronary artery disease (CAD). In a prospective cohort study, we
      examined 1,316 patients without previously diagnosed CAD or diabetes mellitus.
      Patients were participants of the Regensburg Myocardial Infarction Family Study,
      in which > or = 2 family members had severe CAD and 1 had myocardial infarction
      (MI) at < 60 years of age. During a 2-year follow-up, the incidence of first
      cardiovascular events (MI, revascularization, and cardiac death) was compared
      between those with and without the MS at baseline. In all previously unaffected
      family members, the presence of MS increased the hazard ratio for first
      manifestation of CAD by a factor of 1.9 (p = 0.030), which resulted in an event
      rate of 7.1% during follow-up. Specifically in young patients (< or = 50 years
      old, n = 422), we identified the MS as a major event predictor that conferred a
      5.8-fold increased relative risk for first cardiovascular events compared with
      patients without the MS (95% confidence interval 1.4 to 23.8, p = 0.015, event
      rate 6.2%). Remarkably, of the individual MS components, obesity was strongly
      associated with incident MI (relative risk 4.4, 95% confidence interval 1.5 to
      13.0, p = 0.007). Thus, the MS strongly predicts cardiac morbidity and mortality
      in healthy patients with a family background of CAD.

PMID- 16563896
TI  - Association of hemoglobin A(1c) level with the severity of coronary artery
      disease in patients with diabetes mellitus.
AB  - Coronary angiography was performed in 152 men and 163 women with diabetes
      mellitus (mean age 55 +/- 8 years) because of chest pain. The mean hemoglobin
      A(1c) level was 6.66 +/- 0.58% in 132 patients with 0-vessel coronary artery
      disease (CAD), 8.00 +/- 0.84% in 40 patients with 1-vessel CAD, 8.83 +/- 1.45% in
      76 patients with 2-vessel CAD, and 10.40 +/- 2.28% in 67 patients with 3- or 4
      vessel CAD. There was a significant increasing trend of hemoglobin A(1c) levels
      over the increasing number of vessels with CAD (p <0.0001).

PMID- 16563897
TI  - Usefulness of type D personality in predicting five-year cardiac events above and
      beyond concurrent symptoms of stress in patients with coronary heart disease.
AB  - Psychological stress and type D personality have been associated with adverse
      cardiac prognosis, but little is known about their relative effect on the
      pathogenesis of coronary heart disease (CHD). "Type D" refers to the tendency to
      experience negative emotions and to inhibit the expression of these emotions in
      social interactions. We investigated the relative effect of stress and type D
      personality on prognosis at 5-year follow-up. At baseline, 337 patients with CHD
      who participated in cardiac rehabilitation filled in the General Health
      Questionnaire (psychological stress) and the Type D personality scale. Patients
      were followed for 5 years. The end point was major adverse cardiac events, which
      were defined as a composite of cardiac death, myocardial infarction, and cardiac
      revascularization (coronary artery bypass grafting/percutaneous coronary
      intervention). There were 46 major adverse cardiac events at follow-up, including
      4 deaths and 8 myocardial infarctions. Type D patients had an increased risk of
      death/infarction (odds ratio 4.84, 95% confidence interval 1.42 to 16.52, p =
      0.01) compared with non-type D patients, independent of disease severity. Stress
      (p = 0.011) and type D (p = 0.001) were related to an increased risk of
      developing a major adverse cardiac event after adjusting for gender, age, and
      biomedical risk factors. Multivariate analysis yielded left ventricular ejection
      fraction < or =40%, no treatment with coronary artery bypass grafting, and type D
      personality (odds ratio 2.90, 95% confidence interval 1.42 to 5.92, p = 0.003) as
      independent predictors of major adverse cardiac events, whereas psychological
      stress was marginally significant (odds ratio 2.01, 95% confidence interval 0.99
      to 4.11, p = 0.054). In conclusion, type D personality is a psychological factor
      that may optimize risk stratification in patients with CHD. Type D reflects more
      than temporary changes in general stress level because it predicted cardiac
      events after controlling for concurrent symptoms of stress.

PMID- 16563898
TI  - Redefinition of the Q wave -- is there a clinical problem?
AB  - This study evaluated the potential consequences of the redefined joint
      European/American electrocardiographic criteria for an established myocardial
      infarction (MI). New and previous diagnostic Q-wave criteria were used in
      patients with stable angina pectoris. Seventy-nine patients with and 77 patients
      without a documented previous MI were compared using the results of myocardial
      perfusion imaging at rest as a reference. With the new Q-wave criteria, 71% of
      the former group and 40% of the latter had evidence of established MI compared
      with 33% and 3% when using the previous criteria (p <0.0001). Sensitivity,
      specificity, and positive and negative predictive values were 71%, 60%, 64%, and
      67% for the new criteria versus 33%, 97%, 93%, and 59% with the previous
      criteria. These data suggest that that the new Q-wave criteria may be too
      nonspecific, resulting in an inappropriately high number of false-positive
      results.

PMID- 16563899
TI  - Comparison of outcomes in acute myocardial infarction treated with coronary
      angioplasty alone versus coronary stent implantation.
AB  - Randomized trials have demonstrated the superiority of primary angioplasty with
      stent implantation over balloon angioplasty alone in the treatment of acute
      myocardial infarction (AMI). However, it remains unknown whether the beneficial
      outcomes that are attained in clinical trials can be generalized to community
      based practice. We conducted a retrospective cohort study of all patients who
      underwent primary angioplasty for AMI in New York State in 1998 and 1999. In
      total, 6,010 consecutive patients who presented within 23 hours of an AMI were
      identified for this analysis. In-hospital mortality was the primary end point.
      Stents were placed in 5,225 patients (87%). Patients who received stents were
      younger (61 vs 62 years, p = 0.011) and less often women (29% vs 33%, p = 0.018).
      Patients who received stents were less likely to have a history of hypertension
      (56% vs 61%, p = 0.013), diabetes (17% vs 24%, p <0.001), a creatinine level > or
      = 2.5 mg/dl (0.8% vs 2.0%, p = 0.002), 3-vessel coronary disease (14% vs 19%, p
      <0.001), and left main disease (2.4% vs 4.6%, p <0.001). Stent use was associated
      with significant decreases in length of stay (5.9 vs 8.1 day, p <0.001), major
      adverse cardiovascular events (4.1% vs 12%, p <0.001), and in-hospital mortality
      (3.5% vs 9.3%, p <0.001). After multivariate logistic regression analysis to
      adjust for differences in baseline characteristics, stent use was associated with
      a 50% decrease in risk of in-hospital mortality (odds ratio 0.474, 95% confidence
      interval 0.311 to 0.723, p = 0.001).

PMID- 16563900
TI  - Effect of a rapid intra-arterial infusion of dextrose 5% prior to coronary
      angiography on frequency of contrast-induced nephropathy in high-risk patients.
AB  - Contrast-induced nephropathy (CIN) is a common complication of coronary
      angiography that is associated with significant morbidity and mortality.
      Preexisting renal dysfunction is the most important risk factor for the
      development of CIN. A novel strategy of infusing 1 L of 5% dextrose immediately
      before catheterization is associated with a lower rate of CIN in those at high
      risk (creatinine clearance < or = 60 ml/min). CIN occurred in 47 patients (5.7%)
      in the control group and 2 patients (1.4%) in the group treated with 5% dextrose.
      The relative risk decrease was 73% (p = 0.03). This is an effective, quick, and
      inexpensive method of improving outcomes in patients who undergo percutaneous
      coronary interventions.

PMID- 16563901
TI  - Clopidogrel loading dose (300 versus 600 mg) strategies for patients with stable
      angina pectoris subjected to percutaneous coronary intervention.
AB  - We evaluated the effect of high versus low loading doses of clopidogrel in
      patients with stable angina pectoris who underwent percutaneous coronary
      intervention (PCI) on periprocedural events, in-hospital complications, and 30
      day outcomes. The recommended loading dose of clopidogrel for patients with PCI
      is currently 300 mg. Recent studies have suggested that 600 mg may decrease
      periprocedural complications in patients with unstable angina. However, whether
      this holds for patients with stable angina pectoris is unknown. We reviewed
      records of 445 patients with stable angina pectoris who underwent PCI and were
      loaded with 300 mg (n = 126) or 600 mg (n = 319) of clopidogrel immediately
      before the procedure. Study end points were periprocedural ischemic events,
      bleeding complications, and a composite of major adverse cardiac events at 30
      days. Baseline characteristics and procedural indexes were similar between
      groups. Major in-hospital complications were recorded in 2 patients in the 600-mg
      group and in no patient in the 300-mg group (p = 1.00). Postprocedural increase
      of cardiac enzymes (troponin I, p = 0.91; creatinine kinase-MB, p = 0.395) and
      major bleeding (0.6% vs 0%, p = 1.00) were comparable, as was 30-day major
      adverse cardiac events (1.2% vs 0%, p = 0.56). Multivariate analysis did not
      identify any risk decrease for periprocedural myocardial infarction with 600 mg
      of clopidogrel (odds ratio 2.68, 95% confidence interval 0.74 to 9.78, p =
      0.135). In conclusion, in patients with stable angina pectoris, a 300-mg
      clopidogrel loading dose, when given immediately before PCI, is sufficient.
      Although 600 mg was clinically safe, it was not associated with fewer
      periprocedural events and improved 30-day outcomes compared with 300 mg.

PMID- 16563902
TI  - Safety and feasibility of elective high-risk percutaneous coronary intervention
      procedures with left ventricular support of the Impella Recover LP 2.5.
AB  - Currently, the most used left ventricular (LV) support device is intra-aortic
      balloon counterpulsation. The percutaneous implantable Impella Recover LP 2.5
      system is a novel LV (unloading) assist device. We studied the feasibility and
      safety of LV support with the percutaneous implantable Impella Recover LP 2.5
      system in 19 consecutive high-risk patients with percutaneous coronary
      intervention. Procedural success using the device and percutaneous coronary
      intervention was achieved in all 19 patients, who were very poor candidates for
      surgery. The patients were elderly (84% were >60 years of age), 74% had previous
      myocardial infarction, 63% had LV ejection fractions of < or =25%, and all had LV
      ejection fractions of < or =40%. There were no procedural deaths and 2 device
      unrelated in-hospital late deaths. Mean decrease in hemoglobin level was 0.7 +/-
      0.4 mmol/L. The device did not induce or increase aortic valve regurgitation.
      There were no important device-related adverse events during LV support with the
      Impella Recover LP 2.5 system. However, these encouraging findings must be
      confirmed by larger studies, longer assist times, and in other patient
      categories.

PMID- 16563903
TI  - Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term
      mortality after percutaneous coronary intervention.
AB  - The neutrophil to lymphocyte (N/L) ratio is a recently described independent
      predictor of death/myocardial infarction in patients who have undergone coronary
      angiography. We hypothesized that an elevated N/L ratio would be a predictor of
      long-term mortality in patients undergoing percutaneous coronary intervention
      (PCI). A total of 1,046 patients who underwent PCI were divided into tertiles
      based on their preprocedural N/L ratio (mean N/L ratio, tertile 1, 1.7 +/- 0.5;
      tertile 2: 3.2 +/- 0.6; tertile 3, 11.2 +/- 12.9). Vital status was assessed
      using the Social Security Death Index. There were a total of 144 deaths over a
      mean follow-up of 32 months. The best survival was seen in tertile 1, with an
      increase in long-term mortality seen in tertiles 2 and 3 (p <0.0001). In
      multivariable modeling, after adjusting for age, chronic obstructive pulmonary
      disease, left ventricular ejection fraction, serum hemoglobin, serum creatinine,
      and lesion severity, the log N/L, but not the white blood cell count, was an
      independent significant predictor of long-term mortality (hazard ratio 1.85, 95%
      confidence interval 1.3, to 3.04, p = 0.01). The risk persisted when patients
      with an acute myocardial infarction were excluded from the analysis (hazard ratio
      2.46, 95% confidence interval 1.4 to 4.4, p = 0.002). In conclusion, an elevated
      preprocedural N/L ratio in patients undergoing PCI is associated with an
      increased risk of long-term mortality.

PMID- 16563904
TI  - Apolipoprotein-B, low-density lipoprotein cholesterol, and the long-term risk of
      coronary heart disease in men.
AB  - We examined whether plasma apolipoprotein-B (apo-B) levels add further
      information on the risk of coronary heart disease (CHD) after taking into account
      low-density lipoprotein (LDL) cholesterol concentrations and other traditional
      risk factors. Among 2,072 CHD-free men from the Quebec Cardiovascular Study at
      entry and followed for 13 years, 230 had a first CHD event (CHD death or nonfatal
      myocardial infarction). Increased apo-B (tertile 1 vs 3) levels were associated
      with a significant increased risk of CHD after adjustment for nonlipid and lipid
      risk factors other than LDL cholesterol levels (relative risk 1.89, 95%
      confidence interval 1.31 to 2.73). High plasma LDL cholesterol concentrations
      (tertile 1 vs 3) were also associated with an increased risk of CHD independently
      of nonlipid and lipid risk factors (relative risk 2.02, 95% confidence interval
      1.44 to 2.84). However, apo-B levels modulated to a significant extent the risk
      of CHD associated with increased concentrations of LDL cholesterol (>/=4.3
      mmol/L). For instance, among men with high LDL cholesterol levels, those with an
      apo-B level <128 mg/dl were not at increased risk for CHD (relative risk 1.53,
      95% confidence interval 0.89 to 2.62). In contrast, high levels of apo-B and LDL
      cholesterol were associated with a significant twofold increased risk of CHD (p
      <0.001). Receiver-operating curve analysis also indicated that plasma apo-B
      levels improved the ability to discriminate incident CHD cases among patients
      with high LDL cholesterol levels compared with a model based on LDL cholesterol
      levels (p = 0.04). In conclusion, plasma apo-B levels modulated the risk of CHD
      associated with LDL cholesterol over a 13-year follow-up.

PMID- 16563905
TI  - Early effects on endothelial function of atorvastatin 40 mg twice daily and its
      withdrawal.
AB  - Combined hyperlipidemia is associated with endothelial dysfunction. Atorvastatin
      has lipid-lowering and pleiotropic properties, including a protective effect on
      endothelial function. This study investigated the short- and medium-term effects
      of therapy with atorvastatin and of its discontinuation on lipid lowering and
      endothelial function. In 33 patients with combined hyperlipidemia who had been
      randomized and treated for 6 weeks with 40 mg of atorvastatin twice daily (n =
      23) or placebo (n = 10), fasting lipid levels and flow-mediated dilation (FMD) of
      the brachial artery were measured at baseline, after 12 hours, 1 week, and 6
      weeks during therapy, and 36 hours after discontinuation of therapy. Thereafter,
      all patients received 20 mg/day of atorvastatin for another 6 weeks. In the
      atorvastatin group, low-density lipoprotein cholesterol was decreased by 30% and
      46% after 1 and 6 weeks, respectively (p <0.0001 for the 2 comparisons). In
      patients who already showed an impaired FMD at the beginning of the study (n =
      15), atorvastatin caused a significant improvement in FMD, from 2.6% at baseline
      to 4.0% and 6.3% after 1 and 6 weeks, respectively (p <0.05 and <0.001). Thirty
      six hours after withdrawal of atorvastatin, the FMD in this group decreased again
      to 2.8% (p <0.05), whereas low-density lipoprotein cholesterol level remained
      unchanged. The 6 patients with normal FMD at baseline showed no improvement in
      FMD during therapy or any decrease after withdrawal of the drug. In conclusion,
      only patients with endothelial dysfunction profit from high-dose atorvastatin
      treatment. When the treatment is abruptly discontinued, the effect on FMD
      disappears in 36 hours.

PMID- 16563906
TI  - Accuracy of the ratio of triglycerides to high-density lipoprotein cholesterol
      for predicting low-density lipoprotein cholesterol particle sizes, phenotype B,
      and particle concentrations among Asian Indians.
AB  - Asian Indians have unusually high rates of coronary artery disease. Small low
      density lipoprotein (LDL) particle predominance (phenotype B) is associated with
      a fourfold atherogenic risk. This study examined the accuracy of a
      triglyceride/high-density lipoprotein cholesterol (HDL) ratio of > or =3.8
      (determined from the Adult Treatment Panel III guidelines, normal triglycerides
      <150 mg/dl and HDL >40 mg/dl) for predicting phenotype B in Asian Indians.
      Fasting blood samples were collected from 150 healthy Asian Indians. LDL size
      analysis was performed by nuclear magnetic resonance spectroscopy. The
      triglyceride/HDL cholesterol ratio correlated inversely with the LDL size and
      positively with the particle concentration. A triglyceride/HDL cholesterol ratio
      of > or =3.8 had 76% sensitivity, 93% specificity, and 83% positive and 89%
      negative predictive values for predicting phenotype B.

PMID- 16563907
TI  - Relation of social integration to inflammatory marker concentrations in men and
      women 70 to 79 years.
AB  - The lack of social integration has predicted coronary heart disease morbidity and
      mortality in prospective observational studies; however, the biologic mechanisms
      by which this may occur are not well understood. The objective of this study was
      to determine whether social integration is associated with inflammatory risk
      factors for coronary heart disease, specifically C-reactive protein (CRP) and
      interleukin-6. The study participants (aged 70 to 79 years; 380 men and 425
      women) were from the MacArthur Successful Aging Study, a longitudinal study of 3
      community-based cohorts in the United States of older adults with relatively high
      physical and cognitive functioning at baseline (1988 to 1989). The plasma
      concentrations of interleukin-6 and CRP were assessed using a high-sensitivity
      enzyme-linked immunosorbent assay. Cross-sectional logistic regression analyses
      were performed. Multivariate adjusted analyses indicated that social integration
      was significantly inversely associated with CRP concentration in men after
      adjusting for age, race/ethnicity, smoking, alcohol consumption, physical
      activity, body mass index, cardiovascular disease, other major or chronic
      conditions, physical functioning, socioeconomic status, and depression (odds
      ratio 2.23, 95% confidence interval 1.05 to 4.76, for elevated CRP [>3.19 mg/L]
      in the least socially integrated quartile vs the most socially integrated
      quartile). No significant associations were found between social integration and
      interleukin-6 in men or either inflammatory marker in women. In conclusion,
      social integration was negatively associated with the plasma CRP concentration in
      men. These findings suggest a potential biologic mechanism for the observed
      associations between social integration and coronary heart disease in prospective
      studies. Differences may exist between women and men in the biologic pathways
      associated with social integration.

PMID- 16563908
TI  - Contribution of decreased atrial function in the pathogenesis of neurally
      mediated syncope.
AB  - One of the most important mechanisms proposed in the pathogenesis of neurally
      mediated syncope considers the stimulation of myocardial mechanoreceptors as the
      final trigger leading to reflex hypotension and bradycardia. The aim of our study
      was to analyze the modifications of systolic and diastolic velocities of the left
      ventricle by tissue Doppler echocardiography, during the upright tilt test, to
      confirm the presence of an increased ventricular contractility before syncope. We
      evaluated 47 patients (mean age 43 years) with unexplained syncope and 13 healthy
      subjects. Three echocardiographic recordings were collected: at baseline, during
      the initial 5 minutes of the test, and after 15 minutes of tilt. The upright tilt
      test was positive in 28 patients. During the test, all of them had a similar,
      significant, progressive reduction of left ventricular end-diastolic volume, left
      atrial area, and left atrial volume. In contrast, the left ventricular ejection
      fraction showed an early, more pronounced decrease in those with positive tests.
      By tissue Doppler echocardiography, the systolic waves remained almost unchanged,
      and the early filling waves decreased similarly in those with positive or
      negative findings and the controls. In contrast, the atrial filling waves showed
      a significant decrease only in patients with positive tests. In conclusion, our
      study did not find increased ventricular contractility before syncope. In
      contrast, a decreased atrial contribution to ventricular filling characterized
      patients with positive upright tilt test results, which, we postulate, may be an
      important contributory factor to vasovagal syncope.

PMID- 16563909
TI  - Usefulness of mitral annular velocity in predicting exercise tolerance in
      patients with impaired left ventricular systolic function.
AB  - Left ventricular (LV) diastolic function is 1 of the determinants of exercise
      tolerance. However, the relation between early diastolic velocity of the mitral
      annulus (Ea) obtained by tissue Doppler imaging and exercise tolerance is unknown
      in patients with impaired LV systolic function. To investigate the feasibility of
      evaluating exercise tolerance using tissue Doppler imaging, we studied 53
      consecutive patients (mean age 58 +/- 14 years) with a LV ejection fraction of
      <50% (mean 37 +/- 9%). We measured the peak early diastolic velocity of
      transmitral flow (E) and Ea at the lateral border of the mitral annulus and then
      calculated the E/Ea ratio. After echocardiography, we measured the peak oxygen
      consumption and anaerobic threshold (AT) by cardiopulmonary exercise testing. Of
      all the echocardiographic parameters, the best correlation for AT was the E/Ea
      ratio (r = -0.74, p <0.001). Peak oxygen consumption correlated well with Ea and
      the E/Ea ratio (r = 0.64 and r = -0.68, respectively, p <0.001). The AT and peak
      oxygen consumption did not correlate with conventional Doppler indexes. Using an
      AT of 8 ml/min/kg as the cutoff to separate severe exercise intolerance from
      normal, mild, or moderate exercise intolerance, a receiver-operating
      characteristic curve showed that an E/Ea ratio of >11.3 had the best combination
      of sensitivity (88%) and specificity (86%). Exercise tolerance correlated with
      the E/Ea ratio in patients with impaired LV systolic function. In conclusion, the
      evaluation of LV diastolic function using tissue Doppler imaging is useful for
      predicting exercise tolerance in patients with heart failure.

PMID- 16563910
TI  - Association of B-type natriuretic peptide activation to left ventricular end
      systolic remodeling in organic and functional mitral regurgitation.
AB  - B-type natriuretic peptide (BNP) is activated with mitral regurgitation (MR), but
      it is unclear whether BNP activation is uniform in organic and functional MR and
      whether it merely reflects symptoms or is a biomarker of left ventricular (LV)
      geometric and functional alterations. Comprehensive Doppler echocardiography and
      hormonal measurements were performed prospectively in 99 patients, 50 with
      organic MR, 28 with functional MR (with similar LV enlargement 130 +/- 21 vs 141
      +/- 40, p = 0.18, and age 64 +/- 13 vs 66 +/- 12 years, p = 0.56) and 21 controls
      subjects of similar age. Compared with the controls, the patients with MR
      displayed LV remodeling and BNP activation. In those with functional MR compared
      with those with organic MR, despite a lower regurgitant volume (25 +/- 25 vs 96
      +/- 29 ml), higher BNP levels were noted (385 +/- 388 vs 70 +/- 97 pg/ml, p
      <0.0001), even after stratification by functional class (class I 120 +/- 122 vs
      33 +/- 40, class II 318 +/- 470 vs 74 +/- 69, class III to IV 487 +/- 383 vs 268
      +/- 165 pg/ml, p = 0.006). The major determinant of BNP activation was the LV end
      systolic volume index (p <0.0001), independent of MR etiology, symptoms, other
      hormonal activation, and hemodynamic characteristics. The BNP level is a
      biomarker of LV alteration in patients with MR, independent of MR etiology. With
      BNP >90 pg/ml, the odds ratio of an end-systolic volume index value of >/=60
      ml/m(2) was 16 (95% confidence interval 5.5 to 45). In conclusion, BNP activation
      with MR is more pronounced in those with functional than those with organic MR,
      even after stratification for functional class, and independently reflects the
      severity of the LV alteration. Pronounced BNP activation is linked to a higher
      end-systolic volume index, for which it is a biomarker, irrespective of MR
      etiology and symptoms.

PMID- 16563911
TI  - Comparison of findings in patients with versus without atrial fibrillation just
      before isolated mitral valve replacement for rheumatic mitral stenosis (with or
      without associated mitral regurgitation).
AB  - Among 104 patients with mitral stenosis (MS) severe enough or symptomatic enough
      to warrant mitral valve replacement (MVR), 47 (45%) had atrial fibrillation (AF)
      and 57 (55%) had sinus rhythm just before the MVR. Of the latter 57 patients, 21
      (37%) had had previous episodes compatible with AF. If these 21 patients were
      included with the 47 patients with electrocardiographic documentation of AF just
      before MVR, a total of 68 (65%) would have had > or =1 presumed episodes of AF
      before MVR. The 13 patients with previous mitral commissurotomy had a frequency
      of AF similar to that of the 91 whose first operation was MVR. Compared with the
      patients with sinus rhythm just before MVR, those with AF had more heart failure
      (functional class III or IV preoperatively, 79% vs 62%), larger left atria (6.0
      vs 5.2 cm), larger left ventricles in peak systole (4.0 vs 2.6 cm), and more had
      2 or 3 coronary arteries narrowed >50% in diameter (23% vs 10%).

PMID- 16563912
TI  - Frequency of atrial fibrillation in patients having mitral valve repair or
      replacement for pure mitral regurgitation secondary to mitral valve prolapse.
AB  - Relatively little attention has been paid to the frequency of atrial fibrillation
      (AF) in patients with mitral regurgitation (MR) secondary to mitral valve
      prolapse (MVP). We reviewed clinical, electrocardiographic, echocardiographic,
      hemodynamic, and angiographic findings in 246 patients aged 21 to 84 years (mean
      61) (66% men) who had mitral valve repair or replacement for MR secondary to MVP.
      Immediately before the mitral operation by electrocardiogram, only 37 patients
      (15%) had AF and the other 209 patients were in sinus rhythm. Of the latter, 32
      had had a history of AF that had reverted to sinus rhythm spontaneously or with
      antiarrhythmic therapy. Thus, a total of 69 patients (28%) had AF at some time.
      In conclusion, the frequency of AF in patients with MR secondary to MVP and sick
      enough to warrant a mitral valve operation have a relatively low frequency of AF
      (persistent in 15%, paroxysmal in another 13%), percentages considerably lower
      than that seen in patients with mitral stenosis just before a mitral
      commissurotomy or replacement.

PMID- 16563913
TI  - One-year outcome of cardioversion of atrial fibrillation in patients with mitral
      stenosis after percutaneous balloon mitral valvuloplasty.
AB  - Our objectives were to study the success rate of electrical cardioversion after
      percutaneous balloon mitral valvuloplasty (PBMV) in patients with symptomatic
      moderate-to-severe mitral stenosis and atrial fibrillation (AF) and the
      maintenance rate of sinus rhythm for < or =1 year. We studied patients with
      mitral stenosis and AF who were scheduled for PBMV. Electrical cardioversion was
      performed 1 month after PBMV. Amiodarone 200 mg/day was started the day after
      PBMV. The primary outcomes studied were the rate of successful cardioversion and
      the maintenance rate of sinus rhythm at 12 months. Of 272 patients scheduled for
      PBMV, 70 were enrolled. The average age was 45 +/- 10 years. The average mitral
      valve area was 0.82 +/- 0.22 cm(2). Cardioversion was successful in 50 patients
      (71%). Logistic regression analysis revealed that left atrial size and associated
      aortic valvular disease were predictors of successful cardioversion. Of the 50
      patients with successful cardioversion, AF recurred in 24 (48%). An increased
      left atrial diameter was the only factor associated with AF recurrence at 12
      months. In conclusion, good candidates for cardioversion after PBMV were those
      with a left atrial diameter of <60 mm and no associated aortic valvular disease -
      approximately 43% of patients with AF scheduled for PBMV. In this group, about
      2/3 were in sinus rhythm at 12 months after cardioversion.

PMID- 16563914
TI  - Effects of volume and/or pressure overload secondary to congenital heart disease
      (tetralogy of fallot or pulmonary stenosis) on right ventricular function using
      cardiovascular magnetic resonance and B-type natriuretic peptide levels.
AB  - The aim of this study was to analyze the effect of pressure and/or volume
      overload on right ventricular (RV) function and brain natriuretic peptide (BNP)
      levels in patients with surgically corrected congenital heart disease. Forty-two
      consecutive patients aged 17 to 57 years (median 30) with congenital heart
      disease (32 with tetralogy of Fallot and 10 with pulmonary stenosis) were
      examined. The RV systolic pressure was estimated using Doppler echocardiography.
      Cardiovascular magnetic resonance imaging was used to obtain the RV volumes,
      ejection fraction (EF) and corrected EF (cEF). Plasma BNP levels were determined
      by immunoradiometric assay. Patients were categorized as having volume overload
      when pulmonary regurgitation was > or =10% and pressure overload when the RV
      systolic pressure was >40 mm Hg. Patients with RV volume overload had a lower
      RVEF compared with patients with pressure overload (p = 0.02) and lower left
      ventricular EF (p <0.001). BNP was higher in patients with volume overload than
      in patients with pressure overload (p = 0.002). BNP correlated with pulmonary
      regurgitation, RVEF, RV cEF, and left ventricular EF. In linear regression
      analysis, RV cEF was an independent predictor for BNP, after adjustment for age.
      Without the parameter of RV cEF in the regression model, pulmonary regurgitation
      and RVEF were independently associated with BNP level, after adjustment for age.
      In conclusion, patients with RV volume overload had higher BNP levels and lower
      RV function than patients with RV pressure overload. BNP levels were
      independently associated with the degree of RV volume overload and RV function.

PMID- 16563915
TI  - CD44-v6 expression in smooth muscle cells in the postnatal remodeling process of
      ductus arteriosus.
AB  - Closure of the ductus arteriosus (DA) is due to functional constriction followed
      by wall remodeling, with neointimal formation caused by proliferation and
      migration of smooth muscle cells (SMCs) from the media to subendothelium. CD44 is
      a surface cell proteoglycan family. Its isoform, CD44-v6, is only minimally
      expressed in SMCs in the media of normal arteries, but is highly expressed in
      SMCs in the intima and media of injured arteries (e.g., atherosclerosis). Twenty
      two autopsy DA specimens, 11 from full-term babies (age range 2 days to 5 months)
      and 11 from premature babies (age range 3 days to 5 months), with varying degrees
      of ductal wall remodeling, were evaluated by immunohistochemistry using
      antiactin, antifibronectin-extradomain A, anti-leukocyte common antigen, anti
      CD44, and anti-CD44-v6. In DA with wall remodeling, synthetic antifibronectin
      extradomain A-positive SMCs were evident at the neointimal mounds, and the SMCs
      were highly positive for the CD44-v6 isoform, irrespective of gestational age at
      birth. Conversely, SMCs of either closed DAs or persistently patent DAs were CD44
      v6 negative. In conclusion, the present data provide evidence that closure of DA
      involves synthetic SMCs highly positive for CD44-v6, and patent or closed DAs are
      populated by CD44-v6-negative SMCs.

PMID- 16563916
TI  - Comparison of efficacy of medium-sized cutting balloons versus standard balloons
      for dilation of peripheral pulmonary stenosis.
AB  - The efficacy of medium-sized cutting balloons (CBs) 5 to 8 mm in diameter was
      compared with that of standard balloons (SBs) in the dilation of peripheral
      pulmonary stenosis (PPS). Nine vascular lesions in 7 patients were primarily
      dilated by CBs, and 13 vascular lesions in 11 patients were dilated by SBs alone.
      The efficacy of balloon dilation was evaluated by angiography and intravascular
      ultrasound (IVUS). There was no significant difference between the 2 groups in
      the success rate (66% vs 62%), the percentage increase in minimal lesion diameter
      (MLD; median 71% vs 52%) on angiography, and the number of new tears (2 vs 1) on
      IVUS. However, in the subgroup of vascular lesions with MLDs of <4.0 mm, for
      which CBs with diameters >200% of the MLD could have been applied, the percentage
      increase in MLD (95% vs 53%, p <0.05) and the number of tears (2 vs 1, p <0.05)
      with CBs were significantly greater than with SBs, requiring significantly
      smaller maximum balloon pressure (10 vs 13 atm, p <0.05). CBs are as effective as
      conventional balloons in the dilation of PPS and may be more effective when
      larger balloons are available.

PMID- 16563917
TI  - Vasopressin v(2) receptor blockade with tolvaptan versus fluid restriction in the
      treatment of hyponatremia.
AB  - Hyponatremia is common and is associated with a poor prognosis. Traditional
      management with fluid restriction is difficult to maintain, and it is often
      ineffective. The objective of this study was to determine the effect of tolvaptan
      versus fluid restriction on serum sodium concentration. The study was a
      prospective, multicenter, randomized, active-controlled, open-label trial. Twenty
      eight hospitalized subjects with serum sodium <135 mmol/L were enrolled in the
      study. After a 2-day run-in period, subjects were randomized 2:1 to tolvaptan
      alone (n = 17) or fluid restriction (1,200 ml/day) plus placebo (n = 11). Oral
      tolvaptan was started at 10 mg/day and increased to 60 mg/day as needed.
      Treatment was continued for up to 27 days, and follow-up continued for up to 65
      days. The primary end point was the normalization of serum sodium, defined as
      >135 mmol/L or a > or =10% increase from baseline. At the last inpatient visit,
      serum sodium had increased by 5.7 +/- 3.2 mmol/L in the tolvaptan group and 1.0
      +/- 4.7 mmol/L in the fluid restriction group (p = 0.0065). No differences in
      adverse events were observed between the groups. In conclusion, tolvaptan appears
      to be more effective than fluid restriction at correcting hyponatremia in
      hospitalized subjects, without an increase in adverse events.

PMID- 16563918
TI  - Coronary sinus and ascending aortic levels of aldosterone, angiotensin II, and B
      type natriuretic peptide in patients with aortic stenosis and in patients with
      coronary heart disease.
AB  - Demonstration that aldosterone synthesis occurs in the myocardium would suggest
      that the clinical benefits of aldosterone receptor antagonists may extend to
      patients with normal circulating plasma levels of aldosterone. Previous studies
      have reported myocardial aldosterone synthesis in patients with heart failure.
      This study determined whether myocardial aldosterone and angiotensin II release
      occurs in patients with aortic stenosis (AS) and/or coronary heart disease (CHD)
      with normal left ventricular ejection fractions and no clinical heart failure. In
      19 patients with severe AS and 18 patients with stable CHD, plasma levels of
      aldosterone, angiotensin II, B-type natriuretic peptide (BNP), and procollagen
      type III amino terminal peptide (PIIINP) were measured in blood samples taken
      from the coronary sinus and aortic root before diagnostic coronary angiography.
      Plasma aldosterone was approximately 20% greater in the coronary sinus than the
      aorta, respectively, in the 2 patient groups (AS: 120 vs 102 pmol/L, p <0.001;
      CHD: 94 vs 77 pmol/L, p <0.001). Plasma angiotensin II was also greater in the
      coronary sinus (AS: 16 vs 11 pmol/L, p <0.001; CHD: 12 vs 9 pmol/L, p <0.001).
      Plasma levels of BNP in the coronary sinus were approximately double those in the
      aorta in the 2 groups of patients (p <0.001). In contrast, there was no
      transmyocardial gradient in the plasma level of PIIINP for either AS or CHD. In
      conclusion, these results indicate that aldosterone, angiotensin II, and BNP are
      released into the coronary sinus in severe AS and in stable CHD, even when the
      left ventricular ejection fraction is normal and there is no clinical heart
      failure.

PMID- 16563919
TI  - International differences in patient and physician perceptions of "high quality"
      healthcare: a model from pediatric cardiology.
AB  - Although the quality of health care would logically seem to be a universal
      concept, this study hypothesized that physicians and their patients could differ
      in their perceptions of "high-quality care" and that those beliefs might vary by
      country. Such a mismatch in beliefs may be especially important as clinical
      practice guidelines developed in the United States are globalized. A survey of 20
      statements describing various components of health care delivery and quality was
      sent to pediatric cardiologists in 33 countries, who ranked the statements in
      order of priority for ideal health care. Each participating physician
      administered the questionnaire to the parents of children with congenital heart
      disease; 554 questionnaires were received and analyzed. A subanalysis of 9
      countries with the largest number of responses was done (Canada, the Czech
      Republic, France, Germany, Italy, The Netherlands, Sweden, the United Kingdom,
      and the United States). Doctors and parents rated the same 4 statements among the
      top 5: "the doctor is skillful and knowledgeable"; "the doctor explains health
      problems, tests, and treatments in a way the patient can understand"; "a basic
      level of healthcare is available to all citizens regardless of their ability to
      pay"; and "treatment causes the patient to feel physically well." Overall,
      parents' responses differed more among countries than those of physicians; the
      magnitude of the difference between parents and physicians varied by country.
      This discrepancy highlights a potential mismatch between patients' and
      physicians' views about the desired components of health care delivery, in
      particular the application of American quality standards for health care to
      systems in other countries.

PMID- 16563921
TI  - Characteristics and impact of obesity on the outpatient echocardiography
      laboratory.
AB  - The impact of the growing obesity epidemic on the outpatient echocardiography
      laboratory and the characteristics of these patients were retrospectively
      investigated. Over a 6-month period, 916 patients were referred for study, 49.7%
      of whom were obese (body mass index >29.9 kg/m(2)), whereas only 22.3% were
      normal weight (body mass index 18.5 to 25 kg/m(2)). The obese patients were more
      likely to be female, black, older, and referred because of dyspnea or suspected
      heart failure (58.1% vs 36.8%, p <0.001). Despite a poorer quality of
      echocardiographic studies requiring more use of intravenous left heart contrast,
      the left ventricular ejection fraction was estimated in a similar proportion of
      these patients (93.9% vs 96.6%, p = 0.016). However, pulmonary artery systolic
      pressure measurement was less successfully obtained (66.6% vs 80.6%, p = 0.002).
      Thus, the demographics and referral diagnoses of obese patients differ
      significantly from normal weight patients, and body habitus presents unique
      imaging challenges that were only partially met while consuming greater
      resources.

PMID- 16563920
TI  - Differential effects between intravenous and targeted renal delivery of
      fenoldopam on renal function and blood pressure in patients undergoing cardiac
      catheterization.
AB  - A randomized, controlled clinical trial demonstrated that intravenous (IV)
      fenoldopam did not prevent further deterioration in renal function after contrast
      administration in patients with chronic renal insufficiency. This lack of effect
      may have been a consequence of the inability to administer an effective renal
      dose of IV fenoldopam. This study sought to determine whether compared with IV
      administration, selective intrarenal (IR) fenoldopam would increase local
      concentration, leading to a higher glomerular filtration rate (GFR), and, because
      of first-pass renal elimination, result in lower systemic drug levels and less
      decrease in systemic blood pressure (BP). A randomized, controlled, open-label,
      partial crossover design trial was conducted in which 33 patients who underwent
      coronary angiography were randomized in a 1:2 ratio to control or fenoldopam
      (initially IV, then crossed over to IR through a bifurcated renal infusion
      catheter). Compared with IV fenoldopam, IR administration was associated with a
      significantly higher GFR (73.7 +/- 3.1 vs 62.6 +/- 2.5 ml/min, p = 0.0007) and
      renal plasma flow (537.2 +/- 34.0 vs 494.0 +/- 35.5 ml/min, p <0.01), lower
      fenoldopam plasma levels (3.3 +/- 0.3 vs 4.8 +/- 0.3 ng/ml, p <0.0001), and
      greater nadir systolic BP (125.5 +/- 3.6 vs 117.4 +/- 2.8 mm Hg, p <0.0001). Two
      hours after drug discontinuation after contrast administration, GFRs in the
      patients who received IR fenoldopam remained higher than in controls (+15.0
      ml/min [+25%] vs -8.0 ml/min [-14.0%], p <0.05). In conclusion, this pilot trial
      demonstrates that the IR infusion of fenoldopam is safe and practical, producing
      greater renal effect and less reduction of BP than IV infusion. It would be
      appropriate to restudy this renal vasodilator for the prevention of contrast
      nephropathy, using selective IR delivery.

PMID- 16563922
TI  - Effect of long-term cocaine use on regional left ventricular function as
      determined by magnetic resonance imaging.
AB  - This study examined left ventricular (LV) regional midwall circumferential strain
      by cardiac tagged magnetic resonance imaging in 32 long-term cocaine users and 14
      nonusers. Most of the LV segmentations in the cocaine users had less average
      circumferential strain in the systolic and diastolic phases. The average
      diastolic strain in 5 ventricular segmentations was significantly less in the
      cocaine users (p<0.05). In conclusion, long-term cocaine use may be associated
      with regional LV dysfunction, especially diastolic dysfunction.

PMID- 16563923
TI  - Left ventricular function after exercise training in young men.
AB  - The effects of endurance training have been extensively studied in athletes, but
      longitudinal studies of exercise-induced cardiac changes in normal patients are
      limited. To assess the effects of 6 months of moderate-intensity aerobic training
      (1 hour/day, 3 times/week) on normal hearts, 23 sedentary men aged 31.1 +/- 3.5
      years were studied by standard and tissue Doppler echocardiography. Left
      ventricular (LV) systolic function was assessed by the ejection fraction and
      Doppler-measured stroke volume, and diastolic function was assessed by
      transmitral and pulmonary venous flow. Tissue Doppler systolic (Sm), early (Em),
      and late (Am) myocardial velocities were obtained at the septal and lateral
      mitral annulus. After training, there was a 14.5% increase in peak oxygen
      consumption (p = 0.000002) and a decrease in heart rate (60 +/- 7 to 56 +/- 8
      beats/min, p = 0.01). Septal and posterior wall thickness increased (8.7 +/- 1.0
      to 9.4 +/- 1.3 mm, p = 0.002, and 8.2 +/- 0.7 to 8.8 +/- 1.1 mm, p = 0.0009,
      respectively), with a 15% increase in LV mass index (p = 0.0002). LV diameters,
      stroke volumes, and ejection fractions were unchanged. Mitral inflow showed a
      decrease in late-wave velocity (p = 0.00004), thus increasing the early (E)/A
      ratio. Septal and lateral Sm (p = 0.02) and Em velocities (p <0.05) increased
      after training. In conclusion, the physiologic increase in LV mass in response to
      regular exercise in healthy young men occurs in parallel with a decrease in
      atrial contribution to flow. LV function estimated by tissue Doppler is improved
      despite the lack of changes in standard echocardiographic indexes.

PMID- 16563924
TI  - Personal health habits of American cardiologists.
AB  - This study surveyed all cardiologists in a large coalition of cardiology groups.
      A 1-page, 25-item anonymous questionnaire containing 3 sections (demographics,
      medical history, and current medications and supplements) was used. Data from
      returned questionnaires were analyzed and compared with those in national
      databases. Eight hundred surveys were sent, and complete data were available for
      analysis on 471 (59%). The average age of the participants was 48.6 years; 7.1%
      were women. The average body mass index (BMI) was 25 kg/m(2), and 8% were obese
      (BMI > or =30 kg/m(2)); 1.3% were active smokers; 89% exercised > or =1
      time/week; and 72% had > or =1 alcoholic drink/week. Red wine was the most
      frequently consumed alcoholic beverage. Associated cardiovascular risks included
      dyslipidemia (28%), hypertension (14%), and diabetes mellitus (0.6%). Four
      percent had experienced coronary events. Compared with matched cohorts from the
      United States (US) population, cardiologists reported lower rates of
      hypertension, dyslipidemia, and diabetes mellitus, and the rates of smoking and
      obesity were 1/18 and 1/3 those of the US population, respectively. Aspirin and
      statins were each taken daily by about 1/3 of the participants. A cardiologist
      with dyslipidemia was 5 times as likely to be treated and a cardiologist with
      hypertension was almost twice as likely to be treated as an American adult man
      with either of these disorders, respectively. In conclusion, cardiologists appear
      to follow healthier lifestyles than the general adult US population.

PMID- 16563925
TI  - Growth hormone therapy and the heart.
AB  - The growth hormone (GH)-insulin-like growth factor-1 axis has great relevance for
      the regulation of cardiac growth, structure, and function. GH deficiency may
      result in impaired cardiac performance, manifest by a reduction in left
      ventricular mass and ejection fraction, but data are inconsistent. GH therapy is
      recommended treatment in adult patients with GH deficiency, but in acromegaly, in
      which there is excess GH, the main cause of mortality is cardiovascular disease.
      The purposes of this study were to perform (1) a case-controlled study comparing
      cardiac morphology and function in 53 GH-deficient patients (34 men, mean age
      38.1 +/- 15.2 years, 22 with childhood-onset GH deficiency) and 46 healthy
      controls (29 men, mean age 37.8 +/- 12.4 years) and (2) a longitudinal study to
      assess the effect of introducing GH therapy in 37 subjects for a mean period of
      26 +/- 22 months. At study entry, all subjects underwent electrocardiography and
      24-hour ambulatory electrocardiographic monitoring, systolic and diastolic blood
      pressure assessment, detailed echocardiography, and exercise tolerance tests.
      There were no significant differences in left ventricular mass, left ventricular
      dimensions, systolic or diastolic function indexes, or blood pressure at rest in
      patients compared with controls. Exercise duration was significantly shorter and
      peak heart rate during exercise (chronotropic response) lower in the GH
      deficiency group than in controls (p <0.05). After GH treatment, there were no
      significant changes in echocardiographic parameters or blood pressure, but an
      improvement in exercise duration (p = 0.019) was found, particularly in the
      subgroup with childhood-onset GH deficiency (n = 16). In conclusion, patients
      with GH deficiency did not show cardiac structural or functional differences
      compared with healthy controls, with no significant changes after GH treatment.
      However, these patients exhibited improved exercise capacity, especially those
      with childhood-onset GH deficiency.

PMID- 16563927
TI  - Cardiac aldosterone synthesis?

PMID- 16563926
TI  - Prognostic value of routine preoperative electrocardiography in patients
      undergoing noncardiac surgery.
AB  - Electrocardiography is commonly performed as part of preoperative cardiovascular
      risk assessment in patients undergoing noncardiac surgery. However, the
      prognostic value of such electrocardiography is still not clear. This study
      retrospectively studied 23,036 patients who underwent 28,457 surgical procedures
      at Erasmus Medical Center from 1991 to 2000. Patients were screened before
      surgery by type of surgery, cardiovascular risk factors (history of coronary
      heart disease, heart failure, diabetes mellitus, renal dysfunction, and stroke),
      and preoperative electrocardiography. Electrocardiographic (ECG) results showing
      atrial fibrillation, left or right bundle branch block, left ventricular
      hypertrophy, premature ventricular complexes, pacemaker rhythm, or Q-wave or ST
      segment changes were classified as abnormal. Multivariate logistic regression was
      applied to evaluate the relation between ECG abnormalities and cardiovascular
      death. In-hospital cardiovascular death was observed in 199 of 28,457 patients
      (0.7%). Patients with abnormal ECG findings had a greater incidence of
      cardiovascular death than those with normal ECG results (1.8% vs 0.3%; adjusted
      odds ratio 4.5, 95% confidence interval 3.3 to 6.0). Adding ECG data to clinical
      risk factors and the type of surgery resulted in an improved C index for the
      prediction of cardiovascular death (0.79 vs 0.72). However, in patients who
      underwent low-risk or low- to intermediate-risk surgery, the absolute difference
      in the incidence of cardiovascular death between those with and without ECG
      abnormalities was only 0.5%. In conclusion, preoperative electrocardiography
      provides prognostic information in addition to clinical characteristics and the
      type of surgery. However, the usefulness of its routine use in lower risk surgery
      is questionable.

PMID- 16563928
TI  - Identical twins with hypertrophic cardiomyopathy and apical aneurysm.
AB  - Left ventricular apical aneurysms, in absence of coronary artery disease, occur
      in approximately 1% of patients with hypertrophic cardiomyopathy (HC). Identical
      twins, age 44 years, are presented with HC and identical LV morphology, including
      apical aneurysms. These cases demonstrate a genetic predisposition to the
      development of apical aneurysm, as well as overall LV morphology, in patients
      with HC.

PMID- 16563929
TI  - Joseph Loscalzo, MD, PhD: a conversation with the Editor. Interview by William
      Clifford Roberts.

PMID- 16563930
TI  - Cardiovascular health in men attending for abdominal aortic aneurysm screening.

PMID- 16563931
TI  - Wrong approach in relating T-wave abnormalities to coronary artery disease on
      coronary arteriography in the APPROACH study.

PMID- 16563932
TI  - Survival among patients receiving beta-blockers after acute myocardial
      infarction.

PMID- 16563933
TI  - Eisenhower's billion-dollar heart attack.

PMID- 16563934
TI  - Utility of P waves in exercise testing.

PMID- 16563936
TI  - Persistence with bisphosphonate treatment for osteoporosis: finding the root of
      the problem.
AB  - Poor compliance and persistence are among the most significant reasons for failed
      pharmacotherapy encountered in clinical practice. Consequences of poor compliance
      range from minor to serious, depending on drug characteristics, disease state,
      and severity of disease. Compliance and persistence are particular problems for
      patients with a disorder such as osteoporosis, which remains asymptomatic for
      long periods. Poor compliance with bisphosphonate therapy for osteoporosis has
      been associated with a smaller decrease in the rate of bone turnover and smaller
      improvements in bone mineral density, and may potentially result in a higher risk
      of fracture and disability. The compliance problem is additive; complex dosing
      guidelines may contribute to poor compliance with therapy, and the failure to
      follow these guidelines may result in treatment-related adverse events that
      further reduce compliance. In the long term, these issues often result in
      nonpersistence with treatment. In addition to direct consequences for the
      patient, poor compliance is associated with significant healthcare costs. Studies
      suggest that less-frequent dosing regimens improve compliance; however, even
      among patients receiving weekly bisphosphonates, persistence may remain
      suboptimal. Several strategies are available to improve compliance and
      persistence with osteoporosis therapies. Good communication between the
      healthcare provider and the patient--with continuous reinforcement of the
      importance of treatment--is a key approach to improving persistence. Patients
      should receive feedback to confirm that their treatment is having an effect, and
      individualized reminder systems should be recommended to help the patient adhere
      to the treatment plan. Potentially, every patient is liable to discontinue
      treatment even after a long period of regular dosing. It should be assumed that
      every patient receiving therapy for osteoporosis needs regular reinforcement of
      the importance of continuing therapy.

PMID- 16563937
TI  - Improving compliance and persistence with bisphosphonate therapy for
      osteoporosis.
AB  - The successful treatment of patients at increased risk for fracture requires
      proper diagnosis and the development of a treatment plan that permits the patient
      to take medications in accordance with dosing guidelines and on the correct
      schedule. Data indicate that patients with osteoporosis who have good long-term
      medication compliance experience substantially lower risk of fracture.
      Persistence with therapy also correlates with better bone mineral density and
      improved suppression of bone turnover markers. Although bisphosphonates are the
      most potent currently approved antiresorptive agents, they have special dosing
      issues that can have a negative impact on long-term persistence. The
      inconvenience and complexity of some dosing requirements; the potential for
      adverse effects, especially when dosing recommendations are not followed; and
      very low absorption rates--even under ideal conditions--all contribute to poor
      outcomes. Extension of the dosing interval from a once-daily to a once-weekly
      regimen is associated with comparable efficacy, theoretically may improve
      gastrointestinal safety, and is associated with substantial improvement in
      persistence with therapy. However, compliance with weekly regimens remains
      suboptimal. Monthly dosing of ibandronate, a bisphosphonate, was recently
      approved by the US Food and Drug Administration (FDA). Although extending the
      dosing interval may improve compliance and persistence with bisphosphonate
      therapy, it is important to recognize that missed doses or improper dosing may
      have greater consequences with extended dosing intervals. This article highlights
      the importance of educating patients about their diagnosis and long-term
      treatment plan, including the importance of persistence with therapy and
      compliance with dosing recommendations.

PMID- 16563938
TI  - Monitoring osteoporosis therapy: bone mineral density, bone turnover markers, or
      both?
AB  - Monitoring the efficacy associated with antiresorptive therapy is an intuitive
      yet integral part of successful osteoporosis management. Although response rates
      to bisphosphonates in clinical trials--as judged by changes in bone mineral
      density (BMD)--are generally high, a small percentage of compliant patients do
      not respond. Accordingly, monitoring may help identify noncompliant patients and
      allow for other, possibly more successful, therapeutic interventions. Dual energy
      x-ray absorptiometry is the accepted method of assessing BMD to determine the
      need for treatment and to monitor its effects. Change in BMD is considered a
      valid intermediate end point for efficacy of fracture risk reduction. However,
      clinical trials have shown that the reduction in fracture risk associated with
      antiresorptive therapy may occur before changes in BMD become apparent. Vertebral
      fracture benefit is observed even among women who maintain rather than gain BMD
      during antiresorptive therapy. Clinical trials show that suppression of bone
      turnover markers after as little as 3 months of therapy is strongly associated
      with reductions in risk for fracture. Although formal guidelines for monitoring
      bone turnover markers do not yet exist, there are data to suggest that changes in
      these markers are valid intermediate endpoints for efficacy of fracture risk
      reduction that may provide valuable additional data on therapeutic success,
      particularly early in treatment and before changes in BMD become apparent.

PMID- 16563939
TI  - Preventing osteoporosis-related fractures: an overview.
AB  - Osteoporosis is a skeletal disorder characterized by compromised bone strength,
      which predisposes a person to increased risk of fracture. In the United States,
      26% of women aged > or =65 years and >50% of women aged > or =85 years have
      osteoporosis. Over 1.5 million fractures per year are attributable to
      osteoporosis; these fractures result in 500,000 hospitalizations, 800,000
      emergency room visits, 2.6 million physician visits, 180,000 nursing home
      placements, and 12 billion dollars to 18 billion dollars in direct healthcare
      costs each year. Fracture also results in loss of function and has a negative
      impact on psychological status. In recognition of the importance of bone health,
      the US Surgeon General has, for the first time, issued a comprehensive report on
      bone health and treatment. The report recommends a pyramidal approach to
      osteoporosis treatment that includes calcium and vitamin D supplementation,
      physical activity, and fall prevention as the first line in fracture prevention.
      The second level consists of treating secondary causes of osteoporosis; the third
      and top level consists of pharmacotherapy. Pharmacotherapeutic interventions
      (e.g., bisphosphonates, selective estrogen receptor modulators, calcitonin, and
      teriparatide) in women with postmenopausal osteoporosis provide substantial
      reduction in fracture risk over and above risk reduction with calcium and vitamin
      D supplementation alone. Despite the effectiveness of therapy, most patients who
      receive treatment do not remain on treatment for >1 year. An important approach
      to reducing the rate of fractures is first to target our treatments to patients
      at high risk for fracture and then to develop strategies to improve treatment
      continuation rates.

PMID- 16563940
TI  - Approaches to patient education: emphasizing the long-term value of compliance
      and persistence.
AB  - Approximately 50% of patients with chronic disease do not obtain optimal clinical
      benefit from treatment because of poor compliance with medication regimens. Lack
      of compliance is associated with poor clinical outcomes, increased
      hospitalizations, lower quality of life, and higher overall healthcare costs.
      Although poor compliance and persistence are common across many disease states,
      they may be particularly poor in treatment for asymptomatic chronic diseases such
      as osteoporosis. Patient education has been demonstrated to significantly improve
      compliance with medication across a broad range of conditions and disease
      severities. In a study in which patients received educational materials, referral
      for bone densitometry, and physician consultation, 67% were compliant with
      treatment after 6 months. Patient satisfaction with treatment has been linked to
      compliance with therapy; by improving patient care through fulfilling
      expectations for physician visits and providing frequent feedback, the healthcare
      provider can dramatically improve compliance. Self-management programs focusing
      on day-to-day management of chronic diseases have been shown to significantly
      improve heath behaviors and health status. Regardless of the strategy used,
      attention must be directed to identifying the patients least likely to persist
      with treatment and to providing the education and support these patients need to
      adhere to osteoporosis therapy.

PMID- 16563943
TI  - The obese patient with diabetes mellitus: from research targets to treatment
      options.
AB  - Abdominal obesity is a recognized risk factor for both type 2 diabetes mellitus
      and cardiovascular disease. The metabolic consequences of obesity, such as
      insulin resistance and impaired glucose tolerance, are primarily attributable to
      visceral, rather than to subcutaneous, adipose tissue. As a result, liposuction,
      which mainly removes subcutaneous fat, has no significant effect on insulin
      sensitivity; by contrast, weight loss resulting from bariatric surgical
      procedures is associated with resolution of type 2 diabetes in almost 80% of
      patients. Even modest weight loss in overweight or obese individuals is
      associated with significant reductions in the risk of diabetes and increased
      survival. Recent studies have suggested that the renin-angiotensin system (RAS)
      functions in the regulation of adipogenesis. Activation of this system is
      increased in obese individuals and angiotensin II, acting via angiotensin type 1
      receptors, inhibits the differentiation of preadipocytes into mature adipocytes.
      This might be expected to result in ectopic storage of fat in tissues such as
      skeletal muscle and liver, thereby decreasing insulin sensitivity. Evidence from
      animal studies suggests that angiotensin-receptor blockers can promote
      redistribution of excess fat from these ectopic sites to mature adipocytes,
      resulting in improved insulin sensitivity. Clinical trials with telmisartan are
      currently investigating the effects of RAS blockade on insulin sensitivity in
      humans.

PMID- 16563942
TI  - Etiology of insulin resistance.
AB  - Type 2 diabetes mellitus is a major cause of morbidity and mortality worldwide,
      and the prevalence is set to increase dramatically over the coming decades.
      Understanding the metabolic pathways that lead to type 2 diabetes is therefore an
      important healthcare objective. Novel investigational techniques based on
      magnetic resonance spectroscopy (MRS) have allowed real-time insight into the
      molecular defects in patients with type 2 diabetes, revealing that insulin
      resistance is a product of decreased insulin-stimulated skeletal muscle glycogen
      synthesis, which can mostly be attributed to decreased insulin-stimulated glucose
      transport (Glut 4) activity. This defect appears to be a result of intracellular
      lipid-induced inhibition of insulin-stimulated insulin-receptor substrate (IRS)-1
      tyrosine phosphorylation resulting in reduced IRS-1-associated phosphatidyl
      inositol 3 kinase activity. The hypothesis that insulin resistance is a result of
      accumulation of intracellular lipid metabolites (e.g., fatty acyl CoAs,
      diacylglycerol) in skeletal muscle and hepatocytes is supported by observations
      in patients and mouse models of lipodystrophy. Furthermore, the increase in
      hepatic insulin sensitivity observed in patients with type 2 diabetes following
      weight loss is also accompanied by a significant reduction in intrahepatic fat
      without any changes in circulating adipocytokines (interleukin-6, resistin,
      leptin). Finally, recent MRS studies in healthy, lean, elderly subjects and lean
      insulin-resistant offspring of parents with type 2 diabetes have demonstrated
      that reduced mitochondrial activity may also lead to increased intramyocellular
      lipid content and insulin resistance in skeletal muscle in these individuals. In
      summary, in vivo MRS has proved to be an important tool for elucidating the
      causal chain of events that causes insulin resistance. Understanding the cellular
      mechanism(s) of insulin resistance in turn offers the prospect of better targeted
      and more effective therapeutic interventions for treatment and prevention of type
      2 diabetes.

PMID- 16563944
TI  - New treatment strategies for patients with hypertension and insulin resistance.
AB  - The metabolic syndrome is characterized by the clustering of insulin resistance,
      dyslipidemia, and hypertension and is associated with increased risk of
      cardiovascular disease and type 2 diabetes mellitus. However, older
      antihypertensive agents such as thiazide diuretics and beta-blockers have
      potentially adverse effects on glucose and lipid metabolism and may even the
      exacerbate the metabolic syndrome and increase risk of type 2 diabetes. Recent
      clinical trials have suggested that antihypertensive agents that inhibit the
      renin-angiotensin system may reduce risk for new-onset type 2 diabetes, but only
      a few of these studies were placebo controlled, and in most cases, the absolute
      antidiabetic effects were relatively modest. Evidence is accumulating that
      telmisartan, in addition to blocking the angiotensin II type 1 receptor,
      activates the peroxisome proliferator-activated receptor (PPAR)-gamma a well
      known target for treatment of the metabolic syndrome and diabetes. By contrast,
      other angiotensin-receptor blockers are largely devoid of activity on PPAR-gamma.
      Telmisartan is a partial agonist of PPAR-gamma and has a superior tolerability
      profile without causing the fluid retention and edema associated with full
      agonists of PPAR-gamma such as pioglitazone and rosiglitazone. Recent studies
      have indicated that in addition to antidiabetic properties, PPAR-gamma activators
      may also provide protection against atherosclerosis and coronary events. Thus,
      the ability of telmisartan both to activate PPAR-gamma and to block the
      angiotensin receptor may provide added value not only in the treatment of the
      metabolic syndrome and prevention of type 2 diabetes but also in prevention and
      treatment of atherosclerotic cardiovascular disease.

PMID- 16563945
TI  - Risk constellations in patients with the metabolic syndrome: epidemiology,
      diagnosis, and treatment patterns.
AB  - The prevalence of diabetes mellitus is increasing worldwide. Among other
      complications, diabetes is associated with the risk of coronary heart disease
      (CHD) that is thought to be equal to the risk of CHD in subjects without diabetes
      with previous myocardial infarction. Studies have shown that CHD risk factors
      start to increase long before the onset of clinical diabetes. Furthermore, the
      risk factors that are present in prediabetic individuals are also components of
      the highly prevalent metabolic syndrome. This suggests that treatment of CHD risk
      factors may effectively reduce the incidence of type 2 diabetes. Lifestyle
      interventions have proved effective in preventing the onset of type 2 diabetes in
      subjects with impaired glucose tolerance. A number of post hoc studies have
      reported consistent reductions in the incidence of type 2 diabetes in
      hypertensive patients treated with either angiotensin-converting enzyme (ACE)
      inhibitors or angiotensin II receptor blockers (ARBs). As a result of these
      positive data, ongoing prospective studies are investigating whether
      antihypertensive agents prevent or delay the onset of diabetes in patients at
      risk. Telmisartan, a selective oral ARB that is indicated for first-line therapy
      of essential hypertension, may provide improved tolerability compared with ACE
      inhibitors. Therefore, the Ongoing Telmisartan Alone and in Combination with
      Ramipril Global Endpoint Trial (ONTARGET) program is investigating the
      effectiveness of telmisartan in the prevention or delay of type 2 diabetes. The
      program comprises ONTARGET and the Telmisartan Randomized Assessment Study in ACE
      Intolerant Subjects with Cardiovascular Disease (TRANSCEND).

PMID- 16563946
TI  - Heart and kidney: fatal twins?
AB  - The importance of renal function as both a marker of and risk factor for
      cardiovascular disease is increasingly recognized. This link is apparent even in
      the earliest stages of renal dysfunction, at levels that are conventionally
      considered "normal." These findings are of considerable importance, given the
      prevalence of high-normal levels of albuminuria (i.e., 10 to 20 mg/L) in the
      general population. There is also a close link between the progression of
      albuminuria and the development of insulin resistance and type 2 diabetes
      mellitus, such that kidney disease--far from being simply a consequence of the
      metabolic syndrome--may be considered a component of it. It may be hypothesized
      that minor derangements of renal function, such as microalbuminuria or reduced
      glomerular filtration rate, can lead to dysfunction of the endothelium, with the
      consequence of sensitizing the vasculature to the injurious effects of
      hypertension, dyslipidemia, and other risk factors. The renin-angiotensin system
      (RAS) is highly activated in patients with the metabolic syndrome, and this
      presumably is also true for the intrarenal RAS systems. Both angiotensin
      converting enzyme inhibitors and angiotensin II receptor blockers are known to
      reduce the progression of renal damage. Still to be resolved, however, is the
      optimal dosage; several recent studies indicate that the dosage required for
      maximal blood pressure reduction is insufficient to provide maximal
      renoprotection.

PMID- 16563947
TI  - Prevention of loss of renal function over time in patients with diabetic
      nephropathy.
AB  - Management of hypertension is the mainstay of prevention and treatment of
      diabetic renal disease; evidence suggests that tight blood pressure control slows
      renal disease progression in established diabetic nephropathy. Inhibition of the
      renin-angiotensin-aldosterone system (RAAS) has renoprotective effects over and
      above those achieved by lowering systemic blood pressure. To date, however, no
      long-term study using hard end points has directly compared current mechanisms
      for RAAS inhibition, angiotensin II receptor blockade (ARB) and angiotensin
      converting enzyme (ACE) inhibition. This issue was addressed in the recently
      published Diabetics Exposed to Telmisartan and Enalapril (DETAIL) study, a head
      to-head comparison of telmisartan and enalapril in 250 patients with hypertension
      and type 2 diabetes mellitus and early-stage nephropathy. After 5 years'
      treatment, change in glomerular filtration rate (GFR), the primary efficacy end
      point, was equivalent in the 2 treatment groups, as were all secondary end
      points. The expected steep decline in GFR in the first year was followed by a
      lesser decrease in the second year and then almost complete stabilization of
      renal function at > or =3 years. Over 5 years, no patient went into end-stage
      renal disease or required dialysis. There were also no increases in albumin
      excretion rate, nor was there an increase in creatinine beyond 200 mumol/L.
      Incidence of cardiovascular morbidity and mortality was extremely low in both
      treatment groups, a remarkable outcome given that almost 50% of patients had
      evidence of cardiovascular disease at randomization. Inhibition of the RAAS
      should play a major part in management of patients with type 2 diabetes with
      nephropathy, for which both telmisartan and enalapril provide long-term
      renoprotection.

PMID- 16563948
TI  - Special issue: Multiple perspectives on the psychological and neural bases of
      social cognition.

PMID- 16563949
TI  - Mapping of the habenulo-interpeduncular pathway in living mice using manganese
      enhanced 3D MRI.
AB  - This magnetic resonance imaging (MRI) study describes mapping of the habenulo
      interpeduncular pathway in living mice based on manganese-induced contrast. Six
      hours after intracerebroventricular microinjection of MnCl2, T1-weighted 3D MRI
      (2.35 T) at 117 mum isotropic resolution revealed a continuous pattern of
      anterograde labeling from the habenula via the fasciculus retroflexus to the
      interpeduncular nucleus. Alternatively, the less invasive systemic administration
      of MnCl2 allowed for monitoring of the dynamic uptake pattern of respective
      neural components with even higher reproducibility across animals. Time courses
      covered the range from 42 min to 24 h after injection. In conclusion, manganese
      enhanced MRI may open new ways for functional assessments of the habenulo
      interpeduncular system in animal models with cognitive impairment.

PMID- 16563950
TI  - Low-frequency signal changes reflect differences in functional connectivity
      between good readers and dyslexics during continuous phoneme mapping.
AB  - The current fMRI study investigated correlations of low-frequency signal changes
      in the left inferior frontal gyrus, right inferior frontal gyrus and cerebellum
      in 13 adult dyslexic and 10 normal readers to examine functional networks
      associated with these regions. The extent of these networks to regions associated
      with phonological processing (frontal gyrus, occipital gyrus, angular gyrus,
      inferior temporal gyrus, fusiform gyrus, supramarginal gyrus and cerebellum) was
      compared between good and dyslexic readers. Analysis of correlations in low
      frequency range showed that regions known to activate during an "on-off" phoneme
      mapping task exhibit synchronous signal changes when the task is administered
      continuously (without any "off" periods). Results showed that three functional
      networks, which were defined on the basis of documented structural deficits in
      dyslexics and included regions associated with phonological processing, differed
      significantly in spatial extent between good readers and dyslexics. The
      methodological, theoretical and clinical significance of the findings for
      advancing fMRI research and knowledge of dyslexia are discussed.

PMID- 16563951
TI  - Fiber tracking in the cervical spine and inferior brain regions with reversed
      gradient diffusion tensor imaging.
AB  - Diffusion tensor echo planar magnetic resonance imaging of the inferior brain
      regions and the spinal cord suffers from tissue-air and tissue-bone interfaces,
      which cause severe susceptibility-induced artifacts. These artifacts consist of
      image distortions in the phase encode direction and also affect signal intensity.
      To correct for these distortions, we used the reversed gradient method. We find
      that most in-plane voxel displacements in the inferior brain regions and the
      cervical spine can be corrected, yielding a good match of white matter fiber
      tracts with anatomical reference images. Furthermore, uninterrupted white matter
      fiber tracts going from the cervical spine up to cortical areas, derived from
      data acquired in a single acquisition, are presented.

PMID- 16563952
TI  - Cardiac-synchronized gadolinium-enhanced MR angiography: preliminary experience
      for the evaluation of the thoracic aorta.
AB  - Gadolinium (Gd)-enhanced three-dimensional breath-hold magnetic resonance cardiac
      synchronized angiography was performed in 13 patients suspected or known to have
      thoracic aortic disease. High-quality angiograms of the ascending/descending
      thoracic aorta and coronary arteries were obtained with this method. MR
      angiograms were compared with Gd-enhanced angiograms obtained without cardiac
      synchronization. Synchronized imaging showed significantly better aortic valve
      leaflet and proximal coronary artery depiction. Synchronization reduced motion
      artifacts, allowing better visualization of the aortic root and proximal coronary
      arteries.

PMID- 16563953
TI  - Why perfusion in neonates with congenital heart defects is negative--technical
      issues related to pulsed arterial spin labeling.
AB  - Pulsed arterial spin labeling (PASL) perfusion MRI has unique advantages for
      measuring cerebral blood flow (CBF) in the pediatric population. In neonates with
      congenital heart defects (CHDs), however, a considerable number of negative CBF
      values were observed in PASL perfusion images. A set of specific physiological
      and biophysical conditions were proposed as plausible explanations for this
      phenomenon, including small body size, low blood flow, prolonged tracer life time
      (blood T1) and the "shunt" between pulmonary and systemic circulations in CHD. An
      optimized PASL scheme with a restricted label volume was proposed, and
      experimental data demonstrated reduced spurious negative values and lower
      intersubject variability of perfusion measurements in neonates with CHD as
      compared to standard PASL sequences.

PMID- 16563954
TI  - A simple correction for B1 field errors in magnetization transfer ratio
      measurements.
AB  - B1 errors are a problem in magnetization transfer ratio (MTR) measurements
      because the MTR value is dependent on the amplitude of the magnetization transfer
      (MT) pulse. B1 errors can arise from radiofrequency (RF) nonuniformity (caused by
      the RF coil, or skin effect and dielectric resonance in the subject's head) and
      also from inaccurate setting of the transmitter output when compensating for
      varying amounts of loading of the RF coil. B1 errors, and hence MTR errors, may
      be up to 5-10%, a large source of error in quantitative MR measurements.
      Radiofrequency nonuniformity may cause MTR histograms to be broadened. The
      dependence of MTR on B1 was modeled using binary spin bath theory, with a
      continuous wave (CW) approximation. For B1 reductions of up to 20%, normalized
      plots for different brain tissue types could be approximated by a single line,
      indicating that a systematic correction could be applied to MTR measurements with
      a known B1 error, regardless of tissue type. On a 1.5-T scanner with a birdcage
      coil, MTR was measured in 18 tissue types in five controls. The MT pulse
      amplitude was reduced in steps from its nominal value by up to 20%. Averaging
      data over all controls and tissue types resulted in a line fitting
      mtr(normalized)=0.812b(1normalized)+0.193, where mtr(normalized) is the
      normalized value of MTR (relative to its value at the nominal B1) and
      b(1normalized) is the normalized value of B1 (relative to its nominal value). For
      a 20% reduction in MT pulse amplitude (i.e., b(1normalized)=0.80), the mean MTR
      value for the 18 tissue types was 7.0 percent units (pu) below the correct value.
      After correction using the single equation above for all tissue types, all MTR
      values were within 1.5 pu of their correct value [root mean square (rms)
      error=0.7 pu]. Magnetization transfer ratio values tended to be slightly
      overcorrected because the simple linear correction scheme is only an
      approximation to the true MTR dependence on B1. A B1 field mapping technique was
      implemented, based on the double angle method (DAM), with fast spin-echo (FSE)
      readout, and TR=15 s; this took a total of 6 min of imaging time. This was used
      to quantify B(1) errors and correct MTR maps and histograms. However, the
      cerebrospinal fluid (CSF) T1 is very long (approximately 4.2 s); thus, to achieve
      complete longitudinal relaxation (a requirement of the DAM B1 mapping method), an
      increase in TR and, hence, acquisition time would be required. In general,
      however, we are not interested in calculating the B1 in the CSF, although it is
      important that the B1 is determined in partial volume voxels around the CSF.
      Using our birdcage head coil, whole-brain B1 histograms were found to have full
      width half maximums (FWHMs) ranging from just 6.8% to 11.5% of the nominal B1
      value. The FSE DAM B1 field mapping technique was shown to be robust, although a
      longer TR time may be desirable to ensure complete elimination of CSF partial
      volume errors. The procedure can be applied on any scanner where the Euro-MT
      sequence is available, or alternatively, where the amplitude of B1 or of the MT
      pulse can be manually reduced in order to perform this type of "calibration"
      experiment for the particular MTR sequence used. The MTR is known to be highly
      dependent on the parameters of the sequence used, in particular, the MT pulse
      shape, flip angle, duration, and offset frequency, and the repetition time TR'
      between successive MT pulses. Therefore, correction schemes will differ for
      different MTR sequences, and new data sets would be required to calculate these
      different correction schemes.

PMID- 16563955
TI  - Quantitative MRI: a reliable protocol for measurement of cerebral gyrification
      using stereology.
AB  - Stereology is a sampling technique used to generate mathematically unbiased
      estimates of geometric properties of three-dimensional structures based on two
      dimensional slices of the object. Using this method, volume and surface area
      estimates may be generated in a robust, reliable and time-efficient manner based
      on magnetic resonance (MR) image data. We present a method of determining the
      isoperimetric ratio, which may be used as an index of gyrification of the human
      cerebrum, using stereological volume and surface area estimates applied to in
      vivo MR image data. This parameter may be of use in identifying subtle cortical
      developmental malformations in diseases such as epilepsy and schizophrenia. We
      also conduct a series of inter- and intrarater repeatability tests based on 20
      normal brains, which demonstrated the reliability and robustness of stereological
      techniques.

PMID- 16563956
TI  - Sodium and proton diffusion MRI as biomarkers for early therapeutic response in
      subcutaneous tumors.
AB  - The ability to quantitate early effects of tumor therapeutic response using
      noninvasive imaging would have a major impact in clinical oncology. One area of
      active research interest is the ability to use MR techniques to detect subtle
      changes in tumor cellular density. In this study, sodium and proton diffusion MRI
      were compared for their ability to detect early cellular changes in tumors
      treated with a cytotoxic chemotherapy. Subcutaneous 9L gliosarcomas were treated
      with a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea. Both sodium and
      diffusion imaging modalities were able to detect changes in tumor cellularity as
      early as 2 days after treatment, which continued to evolve as increased signal
      intensities reached a maximum approximately 8 days posttreatment. Early changes
      in tumor sodium and apparent diffusion coefficient values were predictive of
      subsequent tumor shrinkage, which occurred approximately 10 days later. Overall,
      therapeutical induced changes in sodium and diffusion values were found to have
      similar dynamic and spatial changes. These findings suggest that these imaging
      modalities detected similar early cellular changes after treatment. The results
      of this study support the continued clinical testing of diffusion MRI for
      evaluation of early tumor treatment response and demonstrate the complementary
      insights of sodium MRI for oncology applications.

PMID- 16563957
TI  - Assessment of absolute blood volume in carcinoma by USPIO contrast-enhanced MRI.
AB  - OBJECTIVES: The characterization of tumor vasculature is essential in studying
      tumor physiology. The aim of this study was to develop a new method - based on
      water proton MR density measurements, in combination with ultrasmall
      superparamagnetic iron oxide (USPIO) administration - to measure absolute blood
      volume (BV) in murine colon carcinoma. MATERIALS AND METHODS: MRI experiments
      were performed at 7 T. CPMG imaging was performed on subcutaneous murine colon
      carcinoma in six mice before and after administration of an USPIO blood-pool
      contrast agent. Density maps were obtained from the signal amplitude at TE=0 of
      the CPMG decay fit. Post-USPIO density maps were subtracted from pre-USPIO
      density maps to quantitatively yield absolute tumor BV maps. In a separate group
      of mice (n=6), the relative vascular area (RVA) of tumors was determined by
      immunohistochemistry. RESULTS: Ultrasmall superparamagnetic iron oxide
      administration resulted in a small decrease in the water proton MR density. The
      BV averaged over the six tumors was 4.6+/-1.6%. The value of the RVA measured by
      immunohistochemical staining was equal to 3.9+/-2.2%. CONCLUSIONS: After
      administration of an USPIO blood-pool agent (T(2) relaxivity > 100 mM(-1) s(-1)),
      the blood water protons become MRI invisible, and pixel-by-pixel BV map can be
      obtained by subtracting the calculated post-USPIO density map from the pre-USPIO
      density map. The value of absolute BV obtained with this novel MR approach is in
      good agreement with the value of the relative vascular measured by
      immunohistochemical staining.

PMID- 16563958
TI  - In vivo isotropic 3D diffusion tensor mapping of the rat brain using diffusion
      weighted 3D MP-RAGE MRI.
AB  - The purpose of this study was to examine the potential of diffusion-weighted (DW)
      three-dimensional (3D) MP-RAGE MRI for diffusion-tensor mapping of the rat brain
      in vivo. A DW-3D-MP-RAGE (3D-DWI) sequence was implemented at 2.0 T using six
      gradient orientations and a b value of 1000 s/mm2. In this sequence, the
      preparation sequence with a "90 degrees RF-motion proving gradient (MPG): MPG-180
      degrees RF-MPG-90 degrees RF" pulse train (DW driven equilibrium Fourier
      transform) was used to sensitize the magnetization to diffusion. A centric k
      space acquisition order was necessary to minimize saturation effects (T1
      contamination) from tissues with short relaxation time. The image matrix was
      128x128x128 (interpolated from 64x64x64 acquisitions), which resulted in small
      isotropic DW image data (voxel size: 0.273x0.273x0.273 mm3). Moreover, 3D-DWI
      derived maps of the fractional anisotropy (FA), relative anisotropy (RA) and main
      diffusion direction were completely free of susceptibility-induced signal losses
      and geometric distortions. Two well-known commissural fibers, the corpus callosum
      and anterior commissure, were indicated and shown to be in agreement with the
      locations of these known stereotaxic atlases. The experiment took 45 min, and
      shorter times should be possible in clinical application. The 3D-DWI sequence
      allows for in vivo 3D diffusion-tensor mapping of the rat brain without motion
      artifacts and susceptibility to distortion.

PMID- 16563959
TI  - T1rho Dispersion profile of rat tissues in vitro at very low locking fields.
AB  - The purpose of this study was to show the T(1rho) dispersion profile in various
      rat tissues (liver, brain, spleen, kidney, heart and skeletal muscle) at low (0.1
      T) B(0) field at very low locking field B1, starting from 10 microT. The T(1rho)
      dispersion profile showed a quite similar pattern in all tissues. The highest
      R(1rho) relaxation rates were seen in the liver and muscle followed by the heart,
      whereas the values for spleen, kidney and brain were rather similar. The greatest
      difference between R2 relaxation rate and R(1rho) relaxation rate at B1=10 microT
      was seen in the liver and muscle. The steepest slope for a dispersion curve was
      seen in the muscle. The value of T(1rho) approximately approached the value of T2
      when the locking field B1 approached 0. Except for the liver, the calculated
      apparent relaxation rate R2' was slightly larger than the calculated one. The
      potential value of T(1rho) imaging is to combine high R1 contrast of low-field
      imaging with the high signal-to-noise ratio (SNR) of high static field imaging.
      T(1rho) relaxation and dispersion data presented in the current study help to
      optimize the rotating-frame MR imaging.

PMID- 16563961
TI  - Functional phantom for fMRI: a feasibility study.
AB  - Functional magnetic resonance imaging (fMRI) reveals changes in blood oxygen
      level-dependent (BOLD) signal after considerable processing. This paper describes
      the implementation and testing of an fMRI phantom where electric current applied
      to a thin wire within a proton-rich medium substituted BOLD distortion of the
      magnetic field; the scanner detects these two distortions as practically
      identical signal changes. The magnitude of the change depended on the current
      strength. The phantom has a number of possible applications. Signal changes
      across sessions, days, instruments and individuals could be monitored. Placing
      the phantom close to a subject during an fMRI experiment could allow
      differentiating sensitivity changes in the scanner due to instrumentation from
      changes in the subject's state and performance during the experiment. The spatial
      extent of brain activations and effects of various changes in the chain of image
      formation could be analyzed using current-induced "activations". Furthermore, the
      phantom could expedite fMRI sequence development by reducing the need to scan
      human subjects, who introduce uncertainty to the signal. Thus, this fMRI phantom
      could be useful for both cognitive fMRI studies and scanner calibration.

PMID- 16563960
TI  - SmartPhantom--an fMRI simulator.
AB  - Many informatics tools have emerged to process the voluminous and complex data
      generated by functional magnetic resonance imaging (fMRI). The interpretation of
      fMRI exams is largely determined by these tools. However, their performance is
      hard to evaluate because there is no independent means of calibration. A novel
      fMRI calibration system called SmartPhantom has been developed to simulate
      functional blood oxygen level dependent (BOLD) imaging. SmartPhantom contains a
      quadrature radio frequency coil, comprising two perpendicular planar loops that
      can be externally activated or deactivated. The system is able to produce
      reasonably uniform signal enhancements in a calibration sample surrounded by the
      two loops during an MRI scan. The enhancement is controlled well in both
      magnitude and predefined timing and produces BOLD-like signals. Characteristics
      of SmartPhantom are discussed in detail, followed by a comparison of fMRI
      informatics tools. Two fMRI data sets are acquired with the SmartPhantom. One
      with high signal-to-noise ratio provides the calibration. Another with lower SNR
      is input into three software packages (BrainVoyager, FSL and Statistical
      Parametric Mapping 2) for data preprocessing and statistical analysis. Results
      from the three packages are compared in both sensitivity of detecting the
      activation and correlation between the predicted activation and calibration.

PMID- 16563962
TI  - Multimodal imaging of the sonic organ of Porichthys notatus, the singing
      midshipman fish.
AB  - The sonic midshipman fish, Porichthys notatus, is a bottom-dwelling species whose
      swim bladder has evolved into a highly specialized, sound-producing organ. The
      males of this species exist in two distinct morphs with different physical
      characteristics and sexual strategies. The Type I males have a much larger sound
      organ and are capable of generating a loud approximately 100 Hz tone continuously
      for over an hour to attract females. This sound is produced by sonic muscle and
      represents one of the most superfast and super-enduring striated muscles found in
      nature. Each fiber contains a hollow, tubular contractile apparatus composed of
      radially arranged myofibrils with extremely broad Z-bands that are supported by a
      desmin-rich cytoskeleton. We have used micro computed tomography (CT) imaging and
      magnetic resonance (MR) imaging to visualize the location of the sonic organ in
      an intact male fish. We have also obtained high-resolution MR images of the
      excised swim bladders from both male types. The images of the Type I sonic organ
      are strikingly detailed and high-contrast, revealing both the internal
      organization of the bladder and the crisscrossing muscle fibers and their mode of
      attachment to the underlying bladder. The high-contrast variation in these images
      is due to different T(2) values for fiber bundles and the spaces between the
      bundles. Direct MR imaging of intact Type I sonic organ in Type I midshipman fish
      is a powerful approach to understanding the contraction of this superfast muscle
      and the oscillation of its bladder to produce mating calls, and how placement of
      the sonic organ in the body of the fish sheds light on its prodigious ability to
      produce and transmit its loud mating call.

PMID- 16563963
TI  - Validation of the proposed International Society for Heart and Lung
      Transplantation grading system for primary graft dysfunction after lung
      transplantation.
AB  - BACKGROUND: A scoring system was recently proposed to grade the severity of
      primary graft dysfunction (PGD), a frequent early complication of lung
      transplantation. The purposes of this study are to: (1) validate the PGD grading
      system with respect to patient outcomes; and (2) compare the performance of
      criteria employing the arterial oxygenation to fraction of inspired oxygen (P/F)
      ratio to an alternative grading system employing the oxygenation index (OI).
      METHODS: We retrospectively reviewed the medical records of 402 patients having
      undergone lung transplantation at our institution from 1992 through 2004. The
      ISHLT PGD grading system was modified and grades were assigned up to 48 hours
      post-transplantation as follows: Grade 1 PGD, P/F > 300; Grade 2, P/F 200 to 300;
      and Grade 3, P/F < 200. A worst score T(0-48) was also assigned, which reflects
      the highest grade recorded between T0 and T48. RESULTS: The prevalence of severe
      PGD (P/F Grade 3) declined after transplant, from 25% at T0 to 15% at T48.
      Grouping patients by P/F grade at T48 demonstrated the clearest differentiation
      of 90-day death rates (Grade 1, 7%; Grade 2, 12%; Grade 3, 33%) (p = 0.0001). T48
      OI grade also differentiates 90-day death rates. There was no difference in
      longer-term survival between patients with PGD Grades 1 and 2. OI grade at T0
      qualitatively improved differential mortality between Grades 1 and 2; however,
      the differences did not reach statistical significance. Patients with a worst
      score T(0-48) of Grade 3 PGD did have significantly decreased long-term survival,
      as well as longer ICU and hospital stay, when compared with Grades 1 and 2 PGD.
      Significant risk factors for short- and long-term mortality in our multivariate
      model were P/F Grade 3 [worst score T(0-48) as well as T0 grade], single-lung
      transplant, use of cardiopulmonary bypass and high pre-operative mean pulmonary
      artery pressure. CONCLUSIONS: There is an increased risk of short- and long-term
      mortality and length of hospital stay associated with severe (Grade 3) PGD. The
      proposed ISHLT grading system can rapidly identify patients with poor outcomes
      who may benefit from early, aggressive treatment. Refinement of the scoring
      system may further improve patient risk stratification.

PMID- 16563964
TI  - Hemodynamics and patient safety during pump-off studies of an axial-flow left
      ventricular assist device.
AB  - BACKGROUND: Axial-flow left ventricular assist devices (LVADs), when inactivated,
      may result in regurgitant blood flow. We assessed the effects of regurgitant pump
      flow with the intraventricular Jarvik 2000 Heart LVAD (Jarvik Heart, Inc., New
      York, NY) on hemodynamics and patient safety under pump-off conditions. METHODS:
      Thirty patients being supported by a Jarvik 2000 as a bridge to heart
      transplantation underwent pump-off studies. Hemodynamics, vital signs and
      cognitive function were monitored; Doppler echocardiographic studies were done
      with the pump turned off for 5 minutes if tolerated. Regurgitant flow was
      assessed in terms of the difference between left ventricular and right
      ventricular outflow tract cardiac output (LVOT CO - RVOT CO). RESULTS: During
      pump-off periods, the mean regurgitant flow was 0.42 +/- 0.41 liter/min, and the
      mean arterial blood pressure was 63.1 +/- 11.6 mm Hg. There was no regurgitant
      flow when the pump was on. Three patients did not tolerate the pump being off for
      periods of 5 minutes; in these tests, the mean regurgitant flow rate was 0.54 +/-
      0.50 liter/min, the mean arterial blood pressure was 52.8 +/- 9.8 mm Hg, and the
      mean pump-off time was 3.1 +/- 1.1 minutes. All patients remained conscious
      during the pump-off period, and none showed lasting adverse effects. CONCLUSIONS:
      Our findings suggest that patients being supported with the axial-flow Jarvik
      2000 Heart LVAD can generally tolerate pump-off times of 5 minutes.

PMID- 16563965
TI  - Improved durability of the HeartMate XVE left ventricular assist device provides
      safe mechanical support up to 1 year but is associated with high risk of device
      failure in the second year.
AB  - BACKGROUND: Life-threatening device failure of the HeartMate VE due to biologic
      inflow valve incompetence or motor failure is a major drawback of long-term
      mechanical support when using this left ventricular assist device (LVAD). The new
      XVE model is the result of recent technical improvements. The aim of this study
      was to compare the clinical performance and durability of the new and earlier
      HeartMate versions. METHODS: We analyzed the incidence of device failure and of
      other device-specific complications (infections, bleeding) in 9 VE and 17 XVE
      patients. Explanted pumps were examined and biologic valve damage classified
      according to a score ranging from 0 (no visible damage) to 3 (severe
      destruction). RESULTS: Mean support time was 145 +/- 92 and 267 +/- 195 days in
      the VE and XVE groups, respectively (difference not significant [NS]). Survival
      was 89% (VE) vs 75% (XVE). The incidence of device failure requiring urgent heart
      transplantation or device replacement was 44% (VE) vs 31% (XVE) (NS). Device
      failure occurred significantly later in the XVE group (200 +/- 34 vs 487 +/- 53
      days, p < 0.01). Causes of device failure were inflow valve incompetence (n = 6)
      and motor failure (n = 3). Acute device failure caused 1 death in the XVE group.
      One XVE patient has been on mechanical support for > 483 days. Macroscopic inflow
      valve damage score after explantation of the devices was 2.2 +/- 1.1 in the VE
      group and 2.0 +/- 0.8 in the XVE group (NS). CONCLUSIONS: The novel HeartMate XVE
      offers greater durability and provides reliable mechanical support in the first
      year. However, there is a high risk of life-threatening device failure in the
      second year. Further technical refinements are necessary to meet the challenges
      of safe long-term circulatory assistance.

PMID- 16563966
TI  - Peripheral vascular reactivity in patients with pulsatile vs axial flow left
      ventricular assist device support.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) are either pulsatile or axial
      flow devices. The latter can be operated at a low-speed setting to allow
      pulsatility or at a high-speed setting to create continuous flow. The purpose of
      this study was to compare the effect of continuous flow and pulsatile flow on
      peripheral vascular reactivity. METHODS: Twenty consecutive patients were divided
      into two groups based on the type of LVAD they received. Ten patients had a
      pulsatile flow LVAD, and 10 had an axial flow LVAD. For the purpose of the study
      protocol, the axial flow devices were operated at a high speed to ensure
      continuous flow. The patients' peripheral artery vasoreactivity was assessed with
      an ultrasound vascular transducer that measured flow-mediated dilation (FMD).
      RESULTS: The FMD of the patients supported with pulsatile flow (15.6 +/- 5%) was
      higher than the FMD of the patients supported with temporary continuous flow (1.8
      +/- 3%). The difference was statistically significant (p < 0.0001). CONCLUSIONS:
      Pulsatile flow is associated with a better peripheral vascular reactivity than
      continuous flow. Patients supported by axial flow devices should be kept on the
      lowest speed setting to allow maximum pulsatility.

PMID- 16563967
TI  - Is native aortic valve commissural fusion in patients with long-term left
      ventricular assist devices associated with clinically important aortic
      insufficiency?
AB  - BACKGROUND: Long-term left ventricular assist device (LVAD) support diminishes
      flow through the native aortic valve and decreases valve motion. This may cause
      aortic valve commissural fusion. The clinical importance of such fusion is not
      well understood. METHODS: Thirty-three consecutive patients receiving long-term
      LVAD support were followed up until transplantation or death. In each case, the
      native aortic valve was examined pathologically for commissural fusion. Pathology
      findings were correlated with hemodynamic performance as assessed by both LVAD
      pump flow and echocardiography. RESULTS: Seventeen of the 33 patients had some
      degree of native aortic valve commissural fusion. Four patients had fusion at 2
      commissures; of these, 2 had clinically significant native valve aortic
      insufficiency (2+ or greater), and 1 exhibited trace insufficiency of the native
      aortic valve. Thirteen patients had fusion at only 1 aortic commissure; of these,
      2 had clinically significant aortic insufficiency (2+ or greater), and 3 had
      trace or mild (1+) insufficiency of native aortic valve. Two of the 4 patients
      with fusion at 2 commissures required increased LVAD support of >3
      liters/min/cm2. No patient with fusion of only 1 commissure required increased
      LVAD support. Three patients with no commissural fusion of the aortic valve
      required increased LVAD support secondary to sepsis. CONCLUSIONS: Commissural
      fusion of the native aortic valve occurs in a significant number of patients
      receiving long-term LVAD support and can necessitate increased levels of LVAD
      support. Recognition of this phenomenon may allow development of strategies to
      minimize commissural fusion and extend LVAD pump life.

PMID- 16563968
TI  - Initial European clinical experience with pulsatile extracorporeal membrane
      oxygenation.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) for post-cardiotomy heart
      failure in neonates and infants still carries high mortality and morbidity rates.
      In this study we present the first European clinical experience with the Medos
      DeltaStream DP1, a new pulsatile flow pump, in neonates and infants. METHODS: The
      DP1 is an extracorporeal rotary blood pump. The pump features a diagonal flow
      impeller, and can be used for both continuous and pulsatile output. Special
      characteristics include its small priming volume of approximately 30 ml and a
      high pumping capacity. A temperature sensor and speed sensors are integrated into
      the pump. The pump has a delivery rate of up to 8 liters/min and a speed range of
      100 to 10,000 rpm. RESULTS: Two patients being assisted with the pulsatile pump
      system were successfully weaned after 36 and 53 hours, respectively. CONCLUSIONS:
      Based on our limited experience with 2 patients, we believe that pulsatile DP1
      device is a reasonable alternative to current conventional non-pulsatile systems.

PMID- 16563969
TI  - Predictors and outcomes of continuous veno-venous hemodialysis use after
      implantation of a left ventricular assist device.
AB  - BACKGROUND: Post-operative renal failure is a common complication after left
      ventricular assist device (LVAD) implantation. This study was designed to
      evaluate predictors and outcomes of acute renal failure after LVAD insertion.
      METHODS: Two-hundred one patients undergoing LVAD implantation at a single
      institution from June 1996 through April 2004 were retrospectively analyzed.
      Patients were categorized into 2 groups: those who required post-operative
      continuous veno-venous hemodialysis (CVVHD) (Group 1, n = 65, 32.3%) and those
      who did not (Group 2, n = 136, 67.7%). Independent predictors of post-operative
      renal failure requiring CVVHD were determined using multivariate logistic
      regression techniques. RESULTS: Patients who had post-operative renal failure
      requiring CVVHD were older (53.7 +/- 12.9 vs 48.2 +/- 14.2 years, p = 0.009), had
      a higher incidence of intra-aortic balloon pump use (46.6% vs 26.2%, p = 0.006),
      and had a higher pre-operative mean LVAD score (5.8 +/- 3.5 vs 3.8 +/- 3.3, p =
      0.001) than those without renal failure. LVAD score was the only independent
      predictor of post-operative renal failure requiring CVVHD (odds ratio = 1.226, p
      = 0.006). Sepsis rate was higher (33.3% vs 6.9%, p < 0.001) and bridge-to
      transplantation rate was lower (52.4% vs 83.5%, p < 0.001) in Group 1 than in
      Group 2. Post-LVAD survival rates at 1, 3, 5 and 7 years for Group 1 and Group 2
      were 43.2%, 39.1%, 34.7% and 34.7% vs 79.2%, 74.0%, 68.3% and 66.4%, respectively
      (log rank, p < 0.001). CONCLUSIONS: Acute renal failure necessitating CVVHD
      remains a serious complication after LVAD and confers significant morbidity and
      mortality. Pre-operative evaluation of patient risk factors and optimization of
      peri-operative hemodynamics are of utmost importance to prevent this major
      complication.

PMID- 16563970
TI  - Cost-effectiveness of pediatric heart transplantation.
AB  - BACKGROUND: Survival after pediatric heart transplantation has continued to
      improve. Nonetheless, graft survival is generally <15 years and the costs of
      transplantation and subsequent immunosuppression are substantial. In the present
      study, we sought to examine the cost-effectiveness of pediatric heart
      transplantation. METHODS: Data from 95 pediatric subjects undergoing
      transplantation at our institution from 1997 through 2004 were reviewed to
      determine the costs of pediatric heart transplantation. Costs included pre
      transplant care, organ procurement, initial hospitalization and follow-up care.
      Life expectancy was derived from the United Network of Organ Sharing data set.
      Data were reported as cost per quality-adjusted life-years (QALYs) gained, which
      were discounted at 3%. Cost-effectiveness was stratified by primary
      transplantation vs re-transplantation. RESULTS: The mean cost of initial
      hospitalization and organ procurement was $221,897 per patient for primary
      transplant and $285,296 per patient for re-transplant. Annual follow-up costs
      were estimated to be $18,141 in the first year (excluding the first 90 days post
      transplant) and $18,480 per year thereafter. Under base-case assumptions, costs
      per QALY gained were $49,679 for primary transplantation and $87,883 for re
      transplantation. Sensitivity analysis yielded a cost-utility range of $44,943 to
      $57,628 per QALY gained for primary transplantation and $70,834 to $103,661 per
      QALY gained for re-transplantation. CONCLUSIONS: Costs of primary pediatric heart
      transplantation are within the accepted range of cost effectiveness. Pediatric
      heart re-transplantation has higher costs relative to benefits gained owing to
      shorter graft survival.

PMID- 16563971
TI  - Pre-transplant soluble CD30 is associated with bronchiolitis obliterans syndrome
      after lung transplantation.
AB  - BACKGROUND: The purpose of this study was to determine the clinical relevance of
      soluble CD30 (sCD30) concentrations in sera from lung transplantation (LTx)
      candidates. METHODS: Soluble CD30 concentrations were determined by enzyme-linked
      immunoassay in pre-transplantation sera of 38 LTx candidates and in serial
      samples taken after LTx from 10 patients. RESULTS: LTx candidates did not have
      increased serum sCD30 concentrations when compared with healthy controls (mean +/
      SE: 22.3 +/- 2.7 vs 26.2 +/- 3.4 U/ml). No relation could be found between age
      and serum sCD30 concentrations, neither in the pre-transplant patients nor in the
      healthy controls. In addition, no differences in sCD30 values could be detected
      between patients sorted by their original type of lung disease. Measurement of
      sCD30 in pre-transplant sera of LTx patients showed that the median concentration
      was 20 U/ml and that LTx patients with low sCD30 (< or = 20 U/ml) had a
      statistically significant (p = 0.039) longer period of freedom from bronchiolitis
      obliterans syndrome (BOS) compared to those with a high sCD30 concentration (> 20
      U/ml). Furthermore, sCD30 concentrations in sera taken at several timepoints
      after LTx remained stable, although a peak could be observed before the clinical
      manifestation of acute rejection (AR). CONCLUSIONS: Soluble CD30 before lung
      transplantation is significantly associated with an increased risk of BOS after
      transplantation.

PMID- 16563972
TI  - The cumulative effect of acute rejection on development of cardiac allograft
      vasculopathy.
AB  - BACKGROUND: Acute rejection increases the inflammatory burden of the transplanted
      organ and predisposes to cardiac allograft vasculopathy (CAV). In this study we
      aim to determine the magnitude of the association, and to differentiate between
      the effects of mild vs severe rejection episodes. METHODS: Between 1988 and 2003,
      489 1-year survivors of heart transplantation underwent 1,435 angiograms. These
      patients were classified as having no CAV (0% stenosis), mild/moderate CAV (<70%)
      or severe CAV (>70%). Acute rejection was considered either mild (Grades 1A, 1B
      and 2 untreated) or moderate/severe (Grade 2 treated on a clinical basis and
      Grades 3A, 3B and 4). We used multi-state Markov models to examine risk factors
      for the onset of CAV. RESULTS: Expressed as relative risk, the onset of CAV was
      significantly increased by donor age (1.26 per 10 years, 95% confidence interval
      [CI] 1.12 to 1.42), male recipient (1.72, 95% CI 1.01 to 2.94), pre-transplant
      recipient ischemic disease (1.53, 95% CI 1.14 to 2.06) and cumulative number of
      moderate/severe rejections (1.10 per episode, 95% CI 1.03 to 1.18). Human
      leukocyte antigen (HLA) and cytomegalovirus (CMV) matching, donor gender,
      recipient age, smoking, cumulative CMV infections and mild rejections were not
      significant risk factors. Estimated annual onset rate of CAV was 11.3% for
      patients with no moderate/severe rejection, rising to 13.6% for those with two
      and 18.0% for those with five such rejections. CONCLUSIONS: Acute moderate/severe
      cellular rejection has a cumulative impact on CAV onset, whereas mild, untreated
      rejection is not associated with CAV.

PMID- 16563973
TI  - Impact of coronary endothelial function on the progression of cardiac transplant
      associated arteriosclerosis: effect of anti-oxidant vitamins C and E.
AB  - BACKGROUND: Excessive vascular oxidant stress has been implicated in cardiac
      transplant-associated arteriosclerosis (TxAA). In a recent placebo-controlled
      study of 40 cardiac transplant recipients, vitamin C 500 mg twice a day and
      vitamin E 400 IU twice a day for 1 year retarded the progression of TxAA, as
      assessed by intravascular ultrasound (IVUS). Endothelial dysfunction is a key
      feature of TxAA and reflects oxidant stress. We hypothesized that coronary
      endothelial dysfunction portends greater TxAA progression and a larger
      therapeutic response to anti-oxidant vitamins. METHODS: In this pre-specified
      analysis, the 40 cardiac transplant recipients were categorized according to
      normal or abnormal coronary endothelial vasomotor function at baseline, as
      assessed by acetylcholine (10(-8) to 10(-6) mol/liter). The effect of anti
      oxidant vitamins within these two groups of patients was assessed by the change
      in intimal index over 1 year using IVUS. RESULTS: With placebo (n = 21), the
      increase in intimal index was greater in the presence vs absence of endothelial
      dysfunction (11 +/- 3% vs 5 +/- 1%, p < 0.05). Among patients with endothelial
      dysfunction (n = 21), the intimal index increased 11 +/- 3% with placebo, but
      decreased -1 +/- 2% with vitamins (p = 0.002). Among patients with normal
      endothelial function (n = 14), the intimal index increased 5 +/- 1% with placebo
      and 1 +/- 1% with vitamins (p < 0.05). CONCLUSIONS: Endothelial dysfunction
      indicates rapid TxAA progression, even in the statin era. Although anti-oxidant
      vitamins reduce disease progression in patients with normal or abnormal
      endothelial function, the magnitude of benefit is larger in patients with
      endothelial dysfunction.

PMID- 16563974
TI  - Five-year results of a randomized, single-center study of tacrolimus vs
      microemulsion cyclosporine in heart transplant patients.
AB  - BACKGROUND: Previous multicenter, randomized trials, lacking standardized post
      transplant protocols, have compared tacrolimus (Tac) and cyclosporine (CyA,
      Sandimmune) and demonstrated similar outcomes with some different adverse
      effects. The microemulsion form of CyA (mCyA, Neoral) has replaced Sandimmune CyA
      as the more widely utilized CyA formulation. This is the first 5-year follow-up
      study of a large, single-center trial (n = 67) under a standardized post
      transplant protocol comparing Tac and mCyA. METHODS: Sixty-seven heart transplant
      patients were randomized to Tac (n = 33) or mCyA (n = 34), both in combination
      with corticosteroids and azathioprine without cytolytic induction. Five-year end
      points included survival, Grade > or = 3A or treated rejection, angiographic
      cardiac allograft vasculopathy (CAV; any lesion > or = 30% stenosis), renal
      dysfunction (creatinine > or = 2.0 mg/dl), use of two or more anti-hypertensive
      medications, percent diabetic and lipid levels. RESULTS: Five-year survival,
      freedom from Grade > or = 3A or any treated rejection and angiographic CAV, mean
      cholesterol level and percent diabetic were similar between the two groups. The
      Tac group had a significantly lower 5-year mean triglyceride level (Tac 97 +/- 34
      vs mCyA 175 +/- 103 mg/dl, p = 0.011) and average serum creatinine level (Tac 1.2
      +/- 0.5 mg/dl vs mCyA 1.5 +/- 0.4 mg/dl, p = 0.044). There was a trend toward
      fewer patients requiring two or more anti-hypertensive drugs in the Tac group
      (Tac 33% vs mCyA 59%, p = 0.065). CONCLUSIONS: Tac and mCyA appear to be
      comparable with regard to 5-year survival, freedom from rejection and CAV.
      However, compared with mCyA, Tac appears to reduce the adverse effect profile for
      hypertriglyceridemia and renal dysfunction and the need for hypertensive
      medications.

PMID- 16563975
TI  - Everolimus in pulmonary transplantation: pharmacokinetics and exposure-response
      relationships.
AB  - BACKGROUND: In this study we evaluated exposure, safety and efficacy data from an
      international trial of everolimus. We sought to identify a tolerated and
      efficacious range for blood levels of this agent in maintenance lung transplant
      recipients. METHODS: In a randomized, double-blind, multicenter trial, 213
      maintenance lung transplant recipients received either everolimus 1.5 mg twice
      daily (n = 101) or azathioprine 1 to 3 mg/kg/day (n = 112) with cyclosporine and
      corticosteroids. At 15 visits over the first 2 years of the trial, we obtained
      826 everolimus trough (C0) blood samples. We used median-effect analysis to
      assess relationships between everolimus C0 vs efficacy and safety responses.
      RESULTS: Everolimus administration began at 1.5 mg twice daily and was
      progressively lowered over the first 2 months to an average of 1.2 +/- 0.4 mg
      twice daily, which was maintained thereafter. This dose yielded median C0 levels
      of 6.6 ng/ml (10th to 90th percentiles: 2.8 to 11.8 ng/ml). Over this range of
      everolimus C0, freedom from a decline in pulmonary function with bronchiolitis
      obliterans syndrome and freedom from biopsy-proven acute rejection were both > or
      = 88%. The incidence of increased cholesterol (> 6.5 mmol/liter), increased
      triglycerides (> 2.9 mmol/liter) and transiently decreased platelet count (< 100
      x 10(9)/liter) rose significantly with increasing C0. Infections and drug-related
      adverse events were not significantly related to exposure. CONCLUSIONS: A
      tolerated and efficacious concentration range for everolimus in maintenance lung
      transplantation appears to be 3 to 12 ng/ml when used in conjunction with
      cyclosporine and corticosteroids. This range should be prospectively assessed
      with possible refinement as more clinical experience is gained.

PMID- 16563976
TI  - Cardiac resynchronization therapy delays heart transplantation in patients with
      end-stage heart failure and mechanical dyssynchrony.
AB  - BACKGROUND: Cardiac dyssynchrony is frequent in advanced heart failure, and
      cardiac resynchronization therapy (CRT) may offer an alternative to heart
      transplantation. We aimed to investigate the impact of CRT on freedom from Tx and
      death in transplant candidates with end-stage heart failure. METHODS: Over a
      period of 2 years, 46 consecutive patients with refractory congestive heart
      failure due to dilated cardiomyopathy were referred for heart transplant
      evaluation. Patients with cardiac dyssynchrony > 107 milliseconds according to
      tissue Doppler imaging (TDI) or QRS duration > 150 milliseconds were treated with
      CRT (CRT group, n = 24), whereas patients without dyssynchrony were not treated
      (non-CRT group, n = 22). RESULTS: At baseline, both groups showed similar
      hemodynamic and functional parameters, including ejection fraction (19 +/- 10% vs
      21 +/- 12%, not statistically significant [NS]) and Vo2max (11.9 +/- 2.0 vs 12.0
      +/- 1.8 ml/kg/min, NS). After a follow-up of 488 +/- 346 days, cumulative
      survival with freedom from transplantation and death was higher in CRT vs non-CRT
      patients (92% vs 39%; p < 0.001). CRT patients showed a decrease in New York
      Heart Association (NYHA) class from 3.2 +/- 1.1 to 2.2 +/- 0.9 (p = 0.003) and an
      increase in Vo2max from 11.9 +/- 2.0 to 13.1 +/- 1.8 ml/kg/min (p = 0.02), and
      71% (17 of 24) of these patients were successfully removed from the waiting list.
      CONCLUSIONS: In heart transplant candidates with significant dyssynchrony, CRT
      delays heart transplantation and improves NYHA class and exercise capacity. For
      these patients, CRT should be considered before heart transplantation.

PMID- 16563977
TI  - Optimal time for post-mortem heparinization in canine lung transplantation with
      non-heart-beating donors.
AB  - BACKGROUND: We previously reported that post-mortem heparinization by closed
      chest cardiac massage is beneficial in lung transplantation from non-heart
      beating donors by preventing formation of microthrombi. In this study, we
      evaluated the optimal time for post-mortem heparinization in canine lung
      transplantation from non-heart-beating donors. METHODS: Left lung transplantation
      was performed in 25 weight-matched pairs of mongrel dogs. Donors were killed with
      an intravenous injection of potassium chloride and left at room temperature for 2
      hours. The cadaver donors were assigned randomly to one of five study groups. In
      Group H0, heparin sodium (1,000 U/kg) was given intravenously before cardiac
      arrest. In Groups H10, H30, H45 and H60, heparin sodium (1,000 U/kg) was given
      intravenously 10, 30, 45 and 60 minutes after cardiac arrest, respectively,
      followed by closed-chest cardiac massage for 2 minutes. After 2 hours of cardiac
      arrest, donor lungs were flushed with low-potassium dextran glucose solution and
      preserved for 60 minutes. After left lung allotransplantation, the right
      pulmonary artery was ligated, and recipient animals were followed up for 3 hours.
      Uni- and multivariate repeat analyses were utilized for statistical assessment.
      RESULTS: After transplantation, gas exchange was significantly worse in Groups
      H45 and H60 than in Groups H0, H10 and H30. Thrombin/anti-thrombin III complex
      concentration during warm ischemia was significantly higher in Groups H30, H45
      and H60 than in Groups H0 and H10. CONCLUSIONS: The optimal time for post-mortem
      heparinization in lung transplantation from non-heart-beating donors is
      approximately 30 minutes after cardiac arrest.

PMID- 16563978
TI  - Outcome analysis of donor gender in heart transplantation.
AB  - BACKGROUND: Several studies have shown a detrimental effect of female donor
      gender on the survival of solid-organ transplant recipients, including heart,
      kidney and liver. We evaluated our own experience in heart transplantation in the
      cyclosporine era, since 1980, to determine the effect of donor gender on
      survival. METHODS: We retrospectively reviewed 869 consecutive patients who
      underwent primary heart transplantation at Stanford University Medical Center
      between December 1980 and March 2004. Actuarial life-table data were calculated
      for survival and freedom from rejection and compared between groups. Multivariate
      Cox proportional hazard analysis was used to identify predictors of reduced long
      term survival. RESULTS: One-year mortality in male recipients who received a
      female donor heart (24%) was higher than in male recipients who received male
      donor heart (13%) (p = 0.009). Actuarial survival rates for male recipients at 1,
      5 and 10 years were 86%, 69% and 50% (with male donor), and 76%, 59% and 45%
      (with female donor) (p = 0.01), respectively. Donor gender had no effect on long
      term survival in male recipients < 45 years of age and female recipients. Female
      donor gender was identified as an independent risk factor for death by
      multivariate analysis, with an odds ratio of 2.3 (95% confidence interval 1.5 to
      3.4, p < 0.001). CONCLUSIONS: In heart transplantation the detrimental effect of
      female donor gender on recipient survival is significant but limited to male
      recipients > 45 years of age. These findings should be considered in the process
      of donor-recipient matching.

PMID- 16563979
TI  - Preliminary experience with bosentan as initial therapy in childhood idiopathic
      pulmonary arterial hypertension.
AB  - Since September 2001, 7 consecutive patients with childhood idiopathic pulmonary
      arterial hypertension (IPAH), a rapidly progressive and fatal condition, have
      been treated with combinations of bosentan, and other therapies
      (sildenafil/warfarin/epoprostenol), at our institution. Survival and clinical
      status in these patients were compared with a group of 12 historic control
      patients who were diagnosed prior to 1997 and received only conventional medical
      therapy. Survival in the bosentan-treated subjects was better than among historic
      controls with comparable disease severity (log rank, p = 0.04). Our findings
      indicate treatment with bosentan permits a delay in IPAH disease progression and,
      in combination with other therapies, improves survival compared with historic
      control patients.

PMID- 16563980
TI  - Cardiac transplantation for pediatric giant cell myocarditis.
AB  - Giant cell myocarditis (GCM) is an organ-specific, autoimmune disease that
      infrequently affects children and generally has a more aggressive (often fatal)
      course than other forms of myocarditis. No data are available about the
      epidemiology of GCM in children. We describe a 13-year-old girl who presented
      with ventricular tachycardia and rapid hemodynamic deterioration that required
      extracorporeal membrane oxygenation (ECMO) as a bridge to heart transplantation.
      Histopathologic examination of the explanted heart revealed GCM. We review the
      demographic features, clinical course and post-transplant immunosuppressive
      therapy of all patients aged 19 years and younger reported to have had GCM.

PMID- 16563981
TI  - Right ventricle-dominant cardiac sarcoidosis with sparing of the left ventricle.
AB  - Cardiac sarcoidosis is a common and often fatal complication of systemic
      sarcoidosis. When present, cardiac sarcoid is generally a diffuse and patchy
      process involving predominantly the left ventricle. We report the case of a
      patient with known cardiac sarcoidosis who underwent cardiac transplantation for
      poorly controlled ventricular tachycardia and heart failure. His explanted heart
      had a previously undescribed distribution of sarcoidosis. This patient had
      complete, circumferential involvement of the right ventricle with near-total loss
      of right ventricular wall myocardium, and secondary marked dilation. The
      interventricular septum was predominantly involved along the right ventricle. The
      cardiac conducting system was also extensively involved, showing granulomatous
      disease. The left ventricular free wall was spared of any gross evidence of
      sarcoidosis. We present the unusual pathologic findings of the explanted heart
      and correlate the results with the patient's clinical data.

PMID- 16563982
TI  - Successful whole blood exchange by apheresis in a patient with acute cyclosporine
      intoxication without long-term sequelae.
AB  - Acute cyclosporine A (CsA) intoxication after organ transplantation may occur
      during the changeover from one form of drug to another, or from miscalculation of
      dosage. Sometimes, it may cause severe hepatotoxicity, nephrotoxicity and
      neurotoxicity. However, the therapeutic plasma exchange for the CsA intoxication
      was not established. Here, we present a case of very severe CsA intoxication
      after cardiac transplantation who recovered from intoxication without long-term
      sequelae via whole blood exchange; therapeutic erythrocytapheresis followed by
      total plasma exchange.

PMID- 16563983
TI  - Recovery of protein-losing enteropathy after living-donor lobar lung
      transplantation in primary pulmonary hypertension.
AB  - The patient investigated was a 43-year-old woman with primary pulmonary
      hypertension (PPH) and refractory protein-losing enteropathy (PLE). She underwent
      living-donor lobar lung transplantation (LDLLT), which led to remarkable
      improvement in both pulmonary hypertension and PLE. Although there have been no
      reports, to our knowledge, that have demonstrated PLE as a complication of PPH,
      the present case clearly shows how PLE could complicate PPH. In addition, and
      more importantly, hypo-proteinemia due to PLE should not necessarily be an
      exclusion criterion for lung transplantation when PPH is involved, because it
      could markedly improve after transplantation.

PMID- 16563984
TI  - Non-compacted hearts require thorough cardiac and neurologic diagnostic work-up.

PMID- 16563985
TI  - Pirfenidone and chronic progressive obliterative airway disease.

PMID- 16563986
TI  - Successful management of asystole with an isolated left ventricular assist
      device.

PMID- 16563987
TI  - Mechanical and biologic analysis of a 1,512-day-long implanted Novacor left
      ventricular assist device.

PMID- 16563988
TI  - High-dose-rate versus low-dose-rate monotherapy in the treatment of localized
      prostate cancer. The case for high-dose-rate monotherapy: An up and coming
      treatment option for low-risk prostate cancer.

PMID- 16563989
TI  - High-dose-rate versus low-dose-rate monotherapy in the treatment of localized
      prostate cancer: The case for low-dose-rate monotherapy.

PMID- 16563992
TI  - Relationship of the International Prostate Symptom score with urinary flow
      studies, and catheterization rates following 125I prostate brachytherapy.
AB  - PURPOSE: Prostate cancer patients undergoing 125I brachytherapy were reviewed. A
      relationship between pretreatment risk factors including International Prostate
      Symptom (IPS) score, urinary flow studies, and posttreatment urinary morbidity
      was assessed. METHODS AND MATERIALS: Pretreatment IPS scores and urinary flow
      studies on 207 patients were reviewed. Relationship between scores and acute
      urinary morbidity was evaluated. RESULTS: Median age, 64 years; median baseline
      IPS score, 9; median prostate volume, 36 cc. Catheterization was required in 18%
      of patients. Baseline IPS score and peak flow rate (PFR) varied inversely,
      demonstrating that PFR for patients requiring a catheter was lower than that for
      those not requiring catheterization. Univariate regression showed that prostate
      volume, prior hormone therapy, and PFR were statistically predictive of
      postimplant urinary retention. For every one-unit increase in PFR, the odds of
      catheterization decreased by 6%. Multivariate analysis demonstrated that only PFR
      and prostate volume were predictive of postimplant urinary retention.
      CONCLUSIONS: Pretreatment IPS questionnaire and urinary flow studies assist in
      predicting risk of urinary morbidity and retention post-125I brachytherapy for
      prostate cancer.

PMID- 16563993
TI  - Robotically assisted prostate brachytherapy with transrectal ultrasound guidance-
      Phantom experiments.
AB  - PURPOSE: To report the preliminary experimental results obtained with a robot
      assisted transrectal ultrasound (TRUS)-guided prostate brachytherapy system.
      METHODS AND MATERIALS: The system consists of a TRUS unit, a spatially
      coregistered needle insertion robot, and an FDA-approved treatment planning and
      image-registered implant system. The robot receives each entry/target coordinate
      pair of the implant plan, inserts a preloaded needle, and then the seeds are
      deposited. The needles/sources are tracked in TRUS, thus allowing the plan to be
      updated as the procedure progresses. RESULTS: The first insertion attempt was
      recorded for each needle, without adjustment. All clinically relevant locations
      were reached in a prostate phantom. Nonparallel and parallel needle trajectories
      were demonstrated. Based on TRUS, the average transverse placement error was 2 mm
      (worst case 2.5 mm, 80% less than 2 mm), and the average sagittal error was 2.5
      mm (worst case 5.0 mm, 70% less than 2.5 mm). CONCLUSIONS: The concept and
      technical viability of robot-assisted brachytherapy were demonstrated in
      phantoms. The kinematically decoupled robotic assistant device is inherently
      safe. Overall performance was promising, but further optimization is necessary to
      prove the possibility of improved dosimetry.

PMID- 16563994
TI  - A simple technique for determining accurate urethral dosimetry after seed
      brachytherapy for prostate cancer.
AB  - PURPOSE: To describe a simple technique to define the anatomically accurate
      urethral location in the postimplant CT scans, after permanent prostate seed
      implants, without the discomfort associated with use of a catheter. METHODS AND
      MATERIALS: We perform preplanned, preloaded transperineal transrectal ultrasound
      guided permanent seed implants for men with low-risk prostate cancer. In
      postimplant CT scans performed 4 weeks after the procedure we previously used a
      catheter to identify the urethra. We now use retrograde injection of contrast,
      followed by the retrograde injection of a mixture of contrast and aerated sterile
      lubricant jelly to opacify the urethra on our CT scans. RESULTS: This technique
      is economical, simple, and more comfortable than the use of a catheter. It
      reliably allows identification of the urethra for the purposes of deriving dose
      volume histogram statistics, for quality control. It provides a reference for
      more accurate determination of the prostate apex. CONCLUSIONS: We recommend this
      technique to those performing prostate seed implants wishing to most accurately
      determine the precise urethral dose parameters in delayed postimplant CT scans,
      without the need for the discomfort associated with a urethral catheter.

PMID- 16563995
TI  - Perioperative high-dose-rate brachytherapy (PHDRB) in previously irradiated head
      and neck cancer: Initial results of a Phase I/II reirradiation study.
AB  - BACKGROUND: This study was undertaken to determine the feasibility of salvage
      surgery and perioperative high-dose-rate brachytherapy (PHDRB) at the
      dose/fractionation schedule proposed in patients with previously irradiated,
      recurrent head and neck cancer or second primary tumors arising in a previously
      irradiated field. METHODS AND MATERIALS: Twenty-five patients were treated with
      surgical resection and PHDRB. The PHDRB dose was 4 Gy b.i.d. x 8 (32 Gy) for R0
      resections and 4 Gy b.i.d. x 10 (40 Gy) for R1 resections. Further external beam
      radiotherapy or chemotherapy was not given. RESULTS: Resections were categorized
      as R0 (negative margins of at least 10 mm) in 3 patients (12.0%) and R1 (negative
      margins of less than 10 mm or microscopically positive margins) in 22 (88.0%).
      Twelve patients with R1 resections had microscopically positive margins (48%),
      and 10 patients had close margins (40%), with a median of 2.0 mm. Ten patients
      (40.0%) developed Radiation Therapy Oncology Group Grade 3 or greater toxicity.
      Seven patients (28%) presented complications requiring a major surgical
      procedure. Four of these complications appeared in the immediate postoperative
      period and were surgical in nature (flap failure, n = 2; fistula, n = 2), and the
      other three were mainly related to the brachytherapy procedure (n = 2) or the
      radiation dose delivered (n = 1). One patient died on postoperative day 11 due to
      bleeding. After a median followup of 14 months, the 4-year local control rate and
      overall survival were 85.6% and 46.4%, respectively. CONCLUSIONS: Surgical
      salvage and PHDRB at the dose/fractionation proposed are feasible in this high
      risk population. Toxicity is high, but not substantially different from other
      reirradiation series. Four-year local control results are encouraging taking into
      account that 22 of 25 patients (88%) had either close or microscopically positive
      margins.

PMID- 16563996
TI  - Predictors of outcome of single-dose brachytherapy for the palliation of
      dysphagia from esophageal cancer.
AB  - BACKGROUND: Single-dose brachytherapy is a commonly used palliative treatment
      modality for esophageal carcinoma, however, a considerable number of patients
      need additional treatment for persistent or recurrent dysphagia. Our aim was to
      establish predictors of an unfavorable outcome after single-dose brachytherapy.
      METHODS AND MATERIALS: Between December 1999 and July 2002, 95 patients with
      dysphagia from inoperable esophageal carcinoma were treated with single-dose (12
      Gy) brachytherapy. Patients were followed-up prospectively by monthly home visits
      by a specialized research nurse. We investigated the patient and tumor
      characteristics that influence the risk of persistent dysphagia (continuing
      dysphagia within 4 weeks after treatment necessitating a second treatment) or
      recurrent dysphagia (occurring more than 4 weeks after treatment) after single
      dose brachytherapy, using logistic and Cox regressions. RESULTS: At 4 weeks after
      brachytherapy, the dysphagia score was improved in 62/84 (74%) patients. Major
      complications occurred in 11/95 (12%) patients. In total, 42/95 (44%) patients
      were treated for persistent (n = 18) and/or recurrent dysphagia (n = 28).
      Persistent dysphagia (n = 18) was caused by persisting obstructing tumor
      confirmed at endoscopy, and these patients were treated with stent placement.
      Patients needing dilation before treatment had a higher risk of persistent
      dysphagia (odds ratio = 4.1; 95% CI 1.3-12). There was a trend toward a higher
      risk of persistent dysphagia for patients previously treated with chemotherapy
      (odds ratio = 3.2; 95% CI 0.81-12). In total, 34 events of recurrent dysphagia
      occurred in 28 patients, caused by obstructing tumor regrowth (n = 26), food
      bolus obstruction (n = 5), or other reasons (n = 3). None of the investigated
      patient and tumor characteristics had a significant association with the risk of
      developing recurrent dysphagia. Of all patients needing additional treatment
      (42/95), those who needed dilation before treatment had a higher risk of
      persistent and/or recurrent dysphagia (hazard ratio = 2.1; 95% CI 1.1-4.1).
      CONCLUSIONS: Patients with stenotic esophageal tumors that cannot be bypassed or
      who previously underwent chemotherapy are poor candidates for single-dose
      brachytherapy. For these patients, a higher and/or fractionated dose of
      brachytherapy or alternative palliative treatment modalities should be
      considered.

PMID- 16563997
TI  - Low-dose-rate vs. high-dose-rate intracavitary brachytherapy for carcinoma of the
      cervix: The University of Alabama at Birmingham (UAB) experience.
AB  - PURPOSE: To review the clinical outcome retrospectively of cervical cancer
      patients treated definitively with either high-dose-rate (HDR) or low-dose-rate
      (LDR) brachytherapy. METHODS AND MATERIALS: One hundred sixty patients (44 Stage
      I, 83 Stage II, and 33 Stage III) were treated from 1990 to 2000 with curative
      intent for carcinoma of the cervix. One hundred three LDR patients were compared
      to 57 HDR patients. Two groups were treated during the same period. An external
      beam dose of 45 Gy to the entire pelvis was delivered at 1.8 Gy per fraction to
      most patients before the first intracavitary insertion in both groups.
      Brachytherapy was delivered in one to two LDR implants or four to five HDR
      implants at 6 Gy per fraction. The prescribed dose to Point A for LDR was at
      least 80-85 Gy. Patient characteristics were similar for each cohort. Point A
      doses were similar for each stage. The primary endpoints assessed were survivals
      and failure sites. Endpoints were estimated using the Kaplan-Meier method and
      comparisons between treatment groups were performed using the log-rank test.
      RESULTS: The median followup was 48 months for the LDR group and 59 months for
      the HDR group. For all stages combined and stage for stage in both groups, there
      was no statistically significant difference in locoregional control, cause
      specific survival, and overall survival for LDR compared with HDR. Locoregional
      control and overall survival were 78% and 60% for LDR compared to 76% and 55% for
      HDR at 3 years, respectively (p = 0.96 and p = 0.48). Median cause-specific
      survival values for LDR vs. HDR were 71 and 81 months, respectively (p = 0.62).
      The cause-specific survival for LDR patients was 62% compared with 59% for HDR
      patients at 3 years. For Stage IB2, II, and III LDR patients, cause-specific
      survival rates were 62%, 67%, and 45%, compared to 67%, 57%, and 33% for HDR at 3
      years, respectively (p = 0.75, p = 0.95, and p = 0.48). For patients with a
      recorded site of first failure, the most common site was locoregional (56%) and
      then distant metastases (26%). Eight patients who were cancer free developed late
      complications requiring surgical intervention. Two patients were in the HDR group
      (3.5%) and 5 in the LDR group (4.8%). CONCLUSIONS: Similar outcome was observed
      for LDR compared with HDR intracavitary brachytherapy for the entire cohort. In
      this review, HDR group was not inferior to LDR group in advanced stages. This is
      likely because our patients were treated with brachytherapy after a high dose of
      external pelvic radiotherapy in both LDR and HDR patients.

PMID- 16563998
TI  - Quality assurance of treatment plans for interstitial and intracavitary high-dose
      rate brachytherapy.
AB  - PURPOSE: Quality assurance for complex high-dose-rate (HDR) treatment planning
      has always been a challenge to the physics community because of the time
      constraint between HDR planning and the delivery of the treatment. This study
      proposes an efficient, precise, and easy method for checking the complex computer
      calculation. METHODS AND MATERIALS: Posttreatment, three-dimensional dose-volume
      study was performed for 98 patients with 128 new treatment plans along with 30
      library plans. Volumes covered by the 100% isodose line, source activity (Ci),
      total dwell time (s), and the prescription dose (100%) were recorded. Variation
      of R(V) defined as (irradiated time x activity/elongation factor x prescribed
      dose) with volume was studied for different catheter systems. RESULTS: Parametric
      fit of R(V) with volume for three different systems that cover most of the
      interstitial and intracavitary brachytherapy implants agrees within +/-6%.
      CONCLUSIONS: The excellent agreement of R(V) derived from this simplistic point
      source model with three-dimensional dose calculations for individual HDR
      treatment plans clearly establishes that for an implant with known number of
      catheters, the time needed to deliver a prescribed dose to a given prescription
      volume can be easily predicted.

PMID- 16563999
TI  - Stem cell research in Brazil: a difficult launch.
AB  - It has been one year since Brazil passed a law enabling scientists to work with
      human embryonic stem cells and to derive new stem cell lines from human embryos.
      But several major hurdles have put human embryonic stem cell research on hold.

PMID- 16564000
TI  - Stem cells and cancer: two faces of eve.
AB  - Recent evidence suggests that a subset of cancer cells within some tumors, the so
      called cancer stem cells, may drive the growth and metastasis of these tumors.
      Understanding the pathways that regulate proliferation, self-renewal, survival,
      and differentiation of malignant and normal stem cells may shed light on
      mechanisms that lead to cancer and suggest better modes of treatment.

PMID- 16564001
TI  - A tiny helper lightens the maternal load.
AB  - In a recent issue of Science, the puzzle of how a large number of maternal mRNAs
      can be coordinately destroyed at the mid-blastula transition of early animal
      embryogenesis is solved. The mysterious agent is not a protein but rather a
      microRNA that is transcribed at this transition point.

PMID- 16564002
TI  - LRP6 holds the key to the entry of anthrax toxin.
AB  - In this issue of Cell, it is demonstrated that the low-density lipoprotein
      receptor-related protein 6 (LRP6) promotes endocytosis of the anthrax toxin into
      cells. LRP6 acts as a coreceptor with either TEM8 or CMG2, the two previously
      identified receptors for anthrax toxin.

PMID- 16564003
TI  - Connecting cancer to the asymmetric division of stem cells.
AB  - Two studies, one in this issue of Cell and the other in Developmental Cell show
      that the cell-fate determinant Brain Tumor (Brat) suppresses self-renewal in one
      of the daughter cells that arise from the asymmetric division of a neural stem
      cell. This work suggests a mechanism by which loss of polarity in stem cells may
      lead to tumorigenesis.

PMID- 16564004
TI  - Increasingly irritable and close to tears: TRPA1 in inflammatory pain.
AB  - TRP cation channels transduce mechanical, thermal, and pain-related inflammatory
      signals. In this issue of Cell, it is reported that TRPA1 has a central role in
      the pain response to endogenous inflammatory mediators and to a diverse array of
      volatile irritants, including those found in tear gas and garlic. In contrast,
      mechano- and thermosensation are normal in TRPA1-deficient mice.

PMID- 16564005
TI  - The KEOPS complex: a rosetta stone for telomere regulation?
AB  - The detailed mechanisms underlying telomere capping and its relationship to
      telomerase activity are still unclear, although many proteins have been
      implicated in either or both processes. In this issue of Cell, the surprising
      identification of a new complex, called KEOPS, which promotes both telomere
      uncapping and elongation is presented.

PMID- 16564006
TI  - Cellular conference call: external feedback affects cell-fate decisions.
AB  - Cells often need to respond to multiple opposing signals simultaneously. In this
      issue of Cell, it is shown that challenging cells with multiple extracellular
      signals induces an external feedback that involves the release of and response to
      additional secreted factors with antagonistic functions. These results suggest
      that an individual cell's decision to die or survive is not wholly independent
      but depends, at least in part, on feedback from its neighbors.

PMID- 16564007
TI  - Structural complexity in ubiquitin recognition.
AB  - Ubiquitinated proteins are sorted into distinct pathways via association with
      several classes of ubiquitin binding domain-containing proteins. A virtual
      explosion in the field of ubiquitin binding proteins has revealed several new
      classes and interactions with distinct surfaces on ubiquitin, providing a clearer
      understanding of how sorting of ubiquitinated proteins is achieved.

PMID- 16564008
TI  - Indicted: worms caught using steroids.
AB  - Three recent papers provide new insights into endocrinology in the worm
      Caenorhabditis elegans. These studies identify natural steroid ligands for the
      DAF-12 nuclear receptor, define a new enzyme in the hormone biosynthetic pathway,
      and clarify the role of endocrine signaling in adult longevity.

PMID- 16564009
TI  - The LDL receptor-related protein LRP6 mediates internalization and lethality of
      anthrax toxin.
AB  - Toxins produced by Bacillus anthracis and other microbial pathogens require
      functions of host cell genes to yield toxic effects. Here we show that low
      density lipoprotein receptor-related protein 6 (LRP6), previously known to be a
      coreceptor for the Wnt signaling pathway, is required for anthrax toxin lethality
      in mammalian cells. Downregulation of LRP6 or coexpression of a truncated LRP6
      dominant-negative peptide inhibited cellular uptake of complexes containing the
      protective antigen (PA) carrier of anthrax toxin moieties and protected targeted
      cells from death, as did antibodies against epitopes in the LRP6 extracellular
      domain. Fluorescence microscopy and biochemical analyses showed that LRP6 enables
      toxin internalization by interacting at the cell surface with PA receptors
      TEM8/ATR and/or CMG2 to form a multicomponent complex that enters cells upon PA
      binding. Our results, which reveal a previously unsuspected biological role for
      LRP6, identify LRP6 as a potential target for countermeasures against anthrax
      toxin lethality.

PMID- 16564010
TI  - A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a
      telomere regulator.
AB  - Telomere capping is the essential function of telomeres. To identify new genes
      involved in telomere capping, we carried out a genome-wide screen in
      Saccharomyces cerevisiae for suppressors of cdc13-1, an allele of the telomere
      capping protein Cdc13. We report the identification of five novel suppressors,
      including the previously uncharacterized gene YML036W, which we name CGI121.
      Cgi121 is part of a conserved protein complex -- the KEOPS complex -- containing
      the protein kinase Bud32, the putative peptidase Kae1, and the uncharacterized
      protein Gon7. Deletion of CGI121 suppresses cdc13-1 via the dramatic reduction in
      ssDNA levels that accumulate in cdc13-1 cgi121 mutants. Deletion of BUD32 or
      other KEOPS components leads to short telomeres and a failure to add telomeres de
      novo to DNA double-strand breaks. Our results therefore indicate that the KEOPS
      complex promotes both telomere uncapping and telomere elongation.

PMID- 16564011
TI  - A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular
      germ cell tumors.
AB  - Endogenous small RNAs (miRNAs) regulate gene expression by mechanisms conserved
      across metazoans. While the number of verified human miRNAs is still expanding,
      only few have been functionally annotated. To perform genetic screens for novel
      functions of miRNAs, we developed a library of vectors expressing the majority of
      cloned human miRNAs and created corresponding DNA barcode arrays. In a screen for
      miRNAs that cooperate with oncogenes in cellular transformation, we identified
      miR-372 and miR-373, each permitting proliferation and tumorigenesis of primary
      human cells that harbor both oncogenic RAS and active wild-type p53. These miRNAs
      neutralize p53-mediated CDK inhibition, possibly through direct inhibition of the
      expression of the tumor-suppressor LATS2. We provide evidence that these miRNAs
      are potential novel oncogenes participating in the development of human
      testicular germ cell tumors by numbing the p53 pathway, thus allowing tumorigenic
      growth in the presence of wild-type p53.

PMID- 16564012
TI  - The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of
      unanchored ubiquitin.
AB  - Ubiquitin binding proteins regulate the stability, function, and/or localization
      of ubiquitinated proteins. Here we report the crystal structures of the zinc
      finger ubiquitin binding domain (ZnF UBP) from the deubiquitinating enzyme
      isopeptidase T (IsoT, or USP5) alone and in complex with ubiquitin. Unlike other
      ubiquitin binding domains, this domain contains a deep binding pocket where the C
      terminal diglycine motif of ubiquitin is inserted, thus explaining the
      specificity of IsoT for an unmodified C terminus on the proximal subunit of
      polyubiquitin. Mutations in the domain demonstrate that it is required for
      optimal catalytic activation of IsoT. This domain is present in several other
      protein families, and the ZnF UBP domain from an E3 ligase also requires the C
      terminus of ubiquitin for binding. These data suggest that binding the ubiquitin
      C terminus may be necessary for the function of other proteins.

PMID- 16564013
TI  - The response of human epithelial cells to TNF involves an inducible autocrine
      cascade.
AB  - Tumor necrosis factor (TNF) is a proinflammatory cytokine that induces
      conflicting pro- and antiapoptotic signals whose relative strengths determine the
      extent of cell death. TNF receptor (TNFR) has been studied in considerable
      detail, but it is not known how crosstalk among antagonistic pro- and
      antiapoptotic signals is achieved. Here we report an experimental and
      computational analysis of crosstalk between prodeath TNF and prosurvival growth
      factors in human epithelial cells. By applying classifier-based regression to a
      cytokine-signaling compendium of approximately 8000 intracellular protein
      measurements, we demonstrate that cells respond to TNF both directly, via
      activated TNF receptor, and indirectly, via the sequential release of
      transforming growth factor-alpha (TGF-alpha), interleukin-1alpha (IL-1alpha), and
      IL-1 receptor antagonist (IL-1ra). We refer to the contingent and time-varying
      series of extracellular signals induced by TNF as an "autocrine cascade." Time
      dependent crosstalk of synergistic and antagonistic autocrine circuits may serve
      to link cellular responses to the local environment.

PMID- 16564014
TI  - Asymmetric segregation of the tumor suppressor brat regulates self-renewal in
      Drosophila neural stem cells.
AB  - How stem cells generate both differentiating and self-renewing daughter cells is
      unclear. Here, we show that Drosophila larval neuroblasts-stem cell-like
      precursors of the adult brain-regulate proliferation by segregating the growth
      inhibitor Brat and the transcription factor Prospero into only one daughter cell.
      Like Prospero, Brat binds and cosegregates with the adaptor protein Miranda. In
      larval neuroblasts, both Brat and Prospero are required to inhibit self-renewal
      in one of the two daughter cells. While Prospero regulates cell-cycle gene
      transcription, Brat acts as a posttranscriptional inhibitor of dMyc. In brat or
      prospero mutants, both daughter cells grow and behave like neuroblasts leading to
      the formation of larval brain tumors. Similar defects are seen in lethal giant
      larvae (lgl) mutants where Brat and Prospero are not asymmetric. We have
      identified a molecular mechanism that may control self-renewal and prevent tumor
      formation in other stem cells as well.

PMID- 16564015
TI  - Type II cadherin ectodomain structures: implications for classical cadherin
      specificity.
AB  - Type I and II classical cadherins help to determine the adhesive specificities of
      animal cells. Crystal-structure determination of ectodomain regions from three
      type II cadherins reveals adhesive dimers formed by exchange of N-terminal beta
      strands between partner extracellular cadherin-1 (EC1) domains. These interfaces
      have two conserved tryptophan side chains that anchor each swapped strand,
      compared with one in type I cadherins, and include large hydrophobic regions
      unique to type II interfaces. The EC1 domains of type I and type II cadherins
      appear to encode cell adhesive specificity in vitro. Moreover, perturbation of
      motor neuron segregation with chimeric cadherins depends on EC1 domain identity,
      suggesting that this region, which includes the structurally defined adhesive
      interface, encodes type II cadherin functional specificity in vivo.

PMID- 16564016
TI  - TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic
      agents.
AB  - TRPA1 is an excitatory ion channel targeted by pungent irritants from mustard and
      garlic. TRPA1 has been proposed to function in diverse sensory processes,
      including thermal (cold) nociception, hearing, and inflammatory pain. Using TRPA1
      deficient mice, we now show that this channel is the sole target through which
      mustard oil and garlic activate primary afferent nociceptors to produce
      inflammatory pain. TRPA1 is also targeted by environmental irritants, such as
      acrolein, that account for toxic and inflammatory actions of tear gas, vehicle
      exhaust, and metabolic byproducts of chemotherapeutic agents. TRPA1-deficient
      mice display normal cold sensitivity and unimpaired auditory function, suggesting
      that this channel is not required for the initial detection of noxious cold or
      sound. However, TRPA1-deficient mice exhibit pronounced deficits in bradykinin
      evoked nociceptor excitation and pain hypersensitivity. Thus, TRPA1 is an
      important component of the transduction machinery through which environmental
      irritants and endogenous proalgesic agents depolarize nociceptors to elicit
      inflammatory pain.

PMID- 16564017
TI  - A lentiviral RNAi library for human and mouse genes applied to an arrayed viral
      high-content screen.
AB  - To enable arrayed or pooled loss-of-function screens in a wide range of mammalian
      cell types, including primary and nondividing cells, we are developing lentiviral
      short hairpin RNA (shRNA) libraries targeting the human and murine genomes. The
      libraries currently contain 104,000 vectors, targeting each of 22,000 human and
      mouse genes with multiple sequence-verified constructs. To test the utility of
      the library for arrayed screens, we developed a screen based on high-content
      imaging to identify genes required for mitotic progression in human cancer cells
      and applied it to an arrayed set of 5,000 unique shRNA-expressing lentiviruses
      that target 1,028 human genes. The screen identified several known and
      approximately 100 candidate regulators of mitotic progression and proliferation;
      the availability of multiple shRNAs targeting the same gene facilitated
      functional validation of putative hits. This work provides a widely applicable
      resource for loss-of-function screens, as well as a roadmap for its application
      to biological discovery.

PMID- 16564018
TI  - Suppression of sodium dodecyl sulfate-polyacrylamide gel electrophoresis sample
      preparation artifacts for analysis of IgG4 half-antibody.
AB  - Human IgG4 subtype antibodies have often been reported to have a significant
      portion (5-50%) of a heavy chain-light chain dimer ("half-antibody") on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), in which the heavy
      chain is not covalently linked through the hinge disulfides to another heavy
      chain. We demonstrate here that there can be artifactual sources of half
      antibody. One occurred during SDS-PAGE sample preparation where rapid disulfide
      scrambling was initiated by preexisting free sulfhydryls in the monoclonal
      antibody (mAb) and by free sulfhydryl produced by destruction of disulfide bonds
      during heating. Inclusion of N-ethylmaleimide in the sample buffer prevented the
      disulfide scrambling. Presumably, cyclization of the flexible IgG4 hinge during
      this disulfide scrambling leads to the preferential separation of heavy chains. A
      second condition producing half-antibody was reoxidation after exposure to
      reductant, where 46% of the antibody was trapped in the intrachain disulfide
      form. The amount of half-antibody was reduced to 4% by reoxidation in the
      presence of a mixture of oxidized and reduced glutathione. When the improved
      sample preparation conditions were used, IgG4 mAb freshly isolated from cells
      contained 4.5-15% half-antibody, indicating that equilibration of the interchain
      and intrachain hinge disulfide pairing was not always attained in cells.

PMID- 16564019
TI  - Kinetic analysis of a high-affinity antibody/antigen interaction performed by
      multiple Biacore users.
AB  - To explore the reliability of Biacore-based assays, 22 study participants
      measured the binding of prostate-specific antigen (PSA) to a monoclonal antibody
      (mAb). Each participant was provided with the same reagents and a detailed
      experimental protocol. The mAb was immobilized on the sensor chip at three
      different densities and a two-step assay was used to determine the kinetic and
      affinity parameters of the PSA/mAb complex. First, PSA was tested over a
      concentration range of 2.5-600 nM to obtain k(a) information. Second, to define
      the k(d) of this stable antigen/antibody complex accurately, the highest PSA
      concentration was retested with the dissociation phase of each binding cycle
      monitored for 1h. All participants collected data that could be analyzed to
      obtain kinetic parameters for the interaction. The association and the extended
      dissociation data derived from the three antibody surfaces were globally fit
      using a simple 1:1 interaction model. The average k(a) and k(d) for the PSA/mAb
      interaction as calculated from the 22 analyses were (4.1+/-0.6) x 10(4) M(-1) s(
      1) and (4.5+/-0.6) x 10(-5) s(-1), respectively. Overall, the experimental
      standard errors in the rate constants were only approximately 14%. Based on the
      kinetic rate constants, the affinity (K(D)) of the PSA/mAb interaction was 1.1+/
      0.2 nM.

PMID- 16564020
TI  - Magnesium and neoplasia: from carcinogenesis to tumor growth and progression or
      treatment.
AB  - Magnesium is involved in a wide range of biochemical reactions that are crucial
      to cell proliferation, differentiation, angiogenesis, and apoptosis. Changes in
      magnesium availability have been shown to influence biological responses of
      immuno-inflammatory cells. Equally plausible seems to be an involvement of
      magnesium in the multistep and interconnected processes that lead to tumor
      formation and development; however, the "how" and "when" of such an involvement
      remain to be defined. Here, we reviewed in vitro and in vivo data that indicated
      a role for magnesium in many biological and clinical aspects of cancer (from
      neoplastic transformation to tumor growth and progression or pharmacologic
      treatment). In adopting this approach we went through a full circle from
      molecular aspects to observational or epidemiological studies that could
      reconcile in a unifying picture the otherwise fragmentary or puzzling data
      currently available on the role of magnesium in cancer.

PMID- 16564021
TI  - A carboxylic residue at the high-affinity, Mn-binding site participates in the
      binding of iron cations that block the site.
AB  - The role of carboxylic residues at the high-affinity, Mn-binding site in the
      ligation of iron cations blocking the site [Biochemistry 41 (2000) 5854] was
      studied, using a method developed to extract the iron cations blocking the site.
      We found that specifically bound Fe(III) cations can be extracted with citrate
      buffer at pH 3.0. Furthermore, citrate can also prevent the photooxidation of
      Fe(II) cations by YZ. Participation of a COOH group(s) in the ligation of Fe(III)
      at the high-affinity site was investigated using 1-ethyl-3-[(3
      dimethylamino)propyl] carbodiimide (EDC), a chemical modifier of carboxylic amino
      acid residues. Modification of the COOH groups inhibits the light-induced
      oxidation of exogenous Mn(II) cations by Mn-depleted photosystem II (PSII[-Mn])
      membranes. The rate of Mn(II) oxidation saturates at > or = 10 microM in PSII(
      Mn) membranes and > or = 500 microM in EDC-treated PSII (-Mn) samples. Intact
      PSII(-Mn) membranes have only one site for Mn(II) oxidation via YZ (dissociation
      constant, Kd = 0.64 microM), while EDC-treated PSII(-Mn) samples have two sites
      (Kd = 1.52 and 22 microM; the latter is the low-affinity site). When PSII(-Mn)
      membranes were incubated with Fe(II) before modifier treatment (to block the high
      affinity site) and the blocking iron cations were extracted with citrate (pH 3.0)
      after modification, the membranes contained only one site (Kd = 2.3 microM) for
      exogenous Mn(II) oxidation by Y(Z)() radical. In this case, the rate of electron
      donation via YZ saturated at a Mn(II) concentration > or = 15 microM. These
      results indicate that the carboxylic residue participating in Mn(II) coordination
      and the binding of oxidized manganese cations at the HAZ site is protected from
      the action of the modifier by the iron cations blocking the HAZ site. We
      concluded that the carboxylic residue (D1 Asp-170) participating in the
      coordination of the manganese cation at the HAZ site (Mn4 in the tetranuclear
      manganese cluster [Science 303 (2004) 1831]) is also involved in the ligation of
      the Fe cation(s) blocking the high-affinity Mn-binding site.

PMID- 16564022
TI  - Protein kinase Cdelta signaling downstream of the EGF receptor mediates migration
      and invasiveness of prostate cancer cells.
AB  - Tumor progression to the invasive phenotype occurs secondary to upregulated
      signaling from growth factor receptors that drive key cellular responses like
      proliferation, migration, and invasion. We hypothesized that Protein kinase
      Cdelta (PKCdelta)-mediated transcellular contractility is required for migration
      and invasion of prostate tumor cells. Two invasive human prostate cancer cell
      lines, DU145 cells overexpressing wildtype human EGFR (DU145WT) and PC3 cells,
      were studied. PKCdelta is overexpressed in these cells relative to normal
      prostate epithelial cells, and is activated downstream of EGFR leading to cell
      motility via modulation of myosin light chain activity. Abrogation of PKCdelta
      using Rottlerin and specific siRNA significantly decreased migration and invasion
      of both cell lines in vitro. Both PKCdelta and phosphorylated PKCdelta protein
      levels were higher in human prostate cancer tissue relative to normal donor
      prostate as assessed by Western blotting and immunohistochemistry. Thus, we
      conclude that PKCdelta inhibition can limit migration and invasion of prostate
      cancer cells.

PMID- 16564023
TI  - Neurabin II mediates doublecortin-dephosphorylation on actin filaments.
AB  - Mutations in the human Doublecortin (DCX) gene cause X-linked lissencephaly, a
      neuronal migration disorder. DCX binds to microtubules and actin filaments.
      Association of Dcx with F-actin is regulated by site-specific phosphorylation and
      by neurabin II, an F-actin binding protein that also binds to Dcx. We show here
      that neurabin II mediates dephosphorylation of Dcx by protein phosphatase 1
      (PP1). Furthermore, overexpression of PP1 reduces Dcx phosphorylation and
      decreases Dcx binding to F-actin. By contrast, abolishing PP1 binding to neurabin
      II maintains phosphorylation levels of Dcx, leading to a retention of Dcx at F
      actin. We suggest that a dynamic regulation of Dcx mediated by neurabin II
      regulates the translocation of Dcx from F-actin to microtubules and vice versa.

PMID- 16564024
TI  - Intrasplenic electro-transfer of IL-4 encoding plasmid DNA efficiently inhibits
      rat experimental allergic encephalomyelitis.
AB  - Most of the previous studies in which cytokine DNA plasmids were delivered by
      systemic administration exhibited only marginal therapeutic effects, if any, in
      the EAE model. One strategy to overcome this limitation would be to determine the
      optimal delivery route leading to significant beneficial effects both in early
      (prophylactic) and late (therapeutic) treatments. To address this issue, we
      directly compared the effects of intrasplenic (i.s.) and intramuscular (i.m.)
      electro-transfer of interleukin-4 (IL-4) DNA in the rat experimental allergic
      encephalomyelitis (EAE) model. In the preventive experiment, rats received i.m.
      (25 or 150 microg) or i.s. (25 microg) administration of IL-4 DNA followed by in
      vivo electroporation the day before MBP immunization. In the late treatment
      experiment, rats were treated with i.m. (150 microg) or i.s. (25 microg)
      administration of IL-4 DNA with electroporation 10 days after MBP immunization.
      As a control the same amount of vector DNA was used. Macroscopic analysis
      indicated that the onset of moderate to severe EAE in rats treated with i.s.
      transfer of 25 microg of IL-4 DNA was prevented on a significant level compared
      with i.m. 25 microg of the IL-4 DNA transfer group or the control group in the
      preventive experiments. More importantly, i.s. transfer of 25 microg of IL-4 DNA
      considerably suppressed the severity of EAE in late treatment experiments while
      i.m. transfer of 150 microg of IL-4 DNA had little effect. The MBP-specific
      expression of IFN-gamma from stimulated splenocytes was considerably decreased by
      the i.s. IL-4 DNA transfer group both in the preventive and therapeutic
      experiments while i.m. transfer had this effect only in the preventive protocol.
      Histological analysis showed that spinal cord inflammation was considerably
      reduced in the i.s. IL-4 DNA transfer group. These data provide the first
      demonstration that i.s. electro-transfer of IL-4 DNA is more effective both in
      the prevention and modulation of EAE than i.m. transfer and that i.s. electro
      gene transfer may present a new approach to cytokine therapy in autoimmune
      diseases.

PMID- 16564025
TI  - Dynamic polymorphism of Ras observed by single molecule FRET is the basis for
      molecular recognition.
AB  - Ras regulates signal transduction pathway function by dynamically interacting
      with various effectors. To understand the basis for Ras function, its
      conformational dynamics were measured in the absence and presence of effectors
      using single molecule fluorescence resonance energy transfer (FRET) between
      probes located on the Switch II region and GTP. The time trajectories of FRET
      efficiency from GTP-bound Ras showed that this conformation spontaneously varies
      among multiple states. Among them, a low FRET state was identified as an inactive
      state. The transition involving the inactive conformational state occurred in the
      time range of seconds. In contrast, fluctuation occurring most probably between
      multiple active high FRET conformational states lasted approximately 30 ms but
      converged to a specific conformational state upon binding to an effector. Thus,
      Ras conformation spontaneously fluctuates to readily interact with various
      effectors.

PMID- 16564026
TI  - Potential regulatory elements of the constitutive up-regulated alpha2(I) collagen
      gene in scleroderma dermal fibroblasts.
AB  - The promoter activity of the full-length alpha2(I) collagen gene is higher in
      scleroderma fibroblasts, when compared to normal fibroblasts. In this study, to
      investigate the molecular mechanisms up-regulating the expression of the
      alpha2(I) collagen gene in scleroderma dermal fibroblasts more clearly, we
      compared promoter activities of serial 5'-deletion mutants and the substitution
      mutants of the alpha2(I) collagen promoter constructs between normal and
      scleroderma fibroblasts. The transient transfection assays using a series of 5'
      deletions of the promoter revealed that the up-regulated fold-increase in
      scleroderma fibroblasts relative to that in normal fibroblasts was significantly
      decreased by the removal of bp -353 to -264 fragment or bp -264 to -186 fragment.
      The substitution mutations introduced into binding sites of Sp1 (bp -303 and 
      271), Ets1 (bp -285 and -282), as well as Smad (bp -263 and -258) also abrogated
      the fold-increase in promoter activity in scleroderma fibroblasts
      synergistically. A DNA affinity precipitation assay showed that the binding
      activity of Ets1 as well as Smad3 to their binding sites was increased in
      scleroderma fibroblasts compared with normal cells. Taken together, our promoter
      analysis emphasized that Ets1 form a transcriptionally active complex with Smad
      and Sp1 by autocrine transforming growth factor (TGF)-beta signaling, leading to
      the intrinsic up-regulation of alpha2(I) collagen promoter activity in
      scleroderma fibroblasts. The blockade of autocrine TGF-beta signaling is thought
      to be one of the most reliable approaches in the treatment of scleroderma, and
      further study targeting Ets1, Smad or Sp1 may contribute to this blockade.

PMID- 16564027
TI  - Sustained neurotensin exposure promotes cell surface recruitment of NTS2
      receptors.
AB  - In this study, we investigated whether persistent agonist stimulation of NTS2
      receptors gives rise to down-regulation, in light of reports that their
      activation induced long-lasting effects. To address this issue, we incubated COS
      7 cells expressing the rat NTS2 with neurotensin (NT) for up to 24 h and measured
      resultant cell surface [125I]-NT binding. We found that NTS2-expressing cells
      retained the same surface receptor density despite efficient internalization
      mechanisms. This preservation was neither due to NTS2 neosynthesis nor recycling
      since it was not blocked by cycloheximide or monensin. However, it appeared to
      involve translocation of spare receptors from internal stores, as NT induced NTS2
      migration from trans-Golgi network to endosome-like structures. This stimulation
      induced regulation of cell surface NTS2 receptors was even more striking in rat
      spinal cord neurons. Taken together, these results suggest that sustained NTS2
      activation promotes recruitment of intracellular receptors to the cell surface,
      thereby preventing functional desensitization.

PMID- 16564028
TI  - Prion infection influences murine endogenous retrovirus expression in neuronal
      cells.
AB  - Prions as causative agents of transmissible spongiform encephalopathies have been
      well investigated in experimental and modelling work. However, little is known
      about the molecular pathogenesis of prion-induced encephalopathies, the role of
      co-factors, and the interaction of prions with cellular components. We
      investigated the influence of prion infection on expression of murine endogenous
      retroviruses (ERVs), which compose approximately 10% of the mouse genome.
      Hypothalamic neuronal cells (GT1) and neuroblastoma cells (N2a) were examined.
      Both cell lines can be persistently infected with mouse adapted prion strains,
      i.e., RML. Using a mammalian retrovirus-specific DNA microarray and quantitative
      PCR methods, we compared the expression profiles of ERVs in prion-infected,
      uninfected, and anti-prion compound-treated murine neuronal cell lines, including
      clonal cell populations. The results suggest that prion infection influences ERV
      expression in neuronal cell lines, that this influence is cell line-specific, ERV
      specific, and responsive to anti-prion compound treatment.

PMID- 16564029
TI  - Colivelin prolongs survival of an ALS model mouse.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease for
      which there is no sufficiently effective therapy. We have reported in our earlier
      study that intracerebroventricular (i.c.v.) injection of activity-dependent
      neurotrophic factor (ADNF) improves motor performance of G93A-SOD1 transgenic
      mice without significant prolongation in survival. Here, we found that i.c.v.
      injection of a synthetic hybrid peptide named Colivelin composed of ADNF and AGA
      (C8R)HNG17, a potent derivative of Humanin that is a bioactive peptide with anti
      Alzheimer's disease activity, dose-dependently improved motor performance and
      prolonged survival of ALS mice. Histological analysis, performed at the age of
      120 days, demonstrated increased motoneuronal survival in spinal cords of
      Colivelin-treated mice as compared with saline- or ADNF-treated mice, indicating
      that Colivelin is a promising neurotrophic peptide for treatment of ALS.

PMID- 16564030
TI  - Beta-catenin control of T-cell transcription factor 4 (Tcf4) importation from the
      cytoplasm to the nucleus contributes to Tcf4-mediated transcription in 293 cells.
AB  - Beta-catenin has essential roles in morphogenesis and human cancer, both as a
      subunit of adhesive complexes in the cell membrane and as a transcriptional
      coactivator in the Wnt signaling pathway. In addition, beta-catenin also has the
      ability to transport lymphoid enhancer binding factor-1 into the nucleus. In this
      study, we examined a constitutive active mutation, beta-catenin (T41A, S45A), for
      its potential as a nuclear import receptor for T-cell transcription factor 4 in
      293 cells. Immunoblot analysis demonstrated that this constitutive active form of
      beta-catenin increased the amount of Tcf4 in the nucleus about 4-5-fold compared
      to controls. However, the overall expression of Tcf4 remained the same with or
      without over-expression of beta-catenin (T41A, S45A). T-cell transcription factor
      4 reporter gene and electrophoretic mobility shift assay further indicated that
      the increase in Tcf4 in the nucleus was consistent with its accrued DNA binding
      capacity and transcription activity. Microscopic immunofluorescence examination
      showed that Tcf4 was mainly located in the cytoplasm and transported into the
      nucleus, without or with over-expression of beta-catenin (T41A, S45A),
      respectively. Our results suggest that beta-catenin might be a major factor
      regulating the import of Tcf4 from the cytoplasm into the nucleus, consequently
      controlling its transcription activity.

PMID- 16564031
TI  - Effects of E-cadherin on mouse embryo implantation and expression of matrix
      metalloproteinase-2 and -9.
AB  - E-cadherin is a cell surface glycoprotein, which is responsible for adhesion
      between epithelial cells. Whether it is involved in embryo implantation is still
      unknown. In a mouse intrauterine horn injection model, one uterine horn in each
      mouse was injected with different doses of E-cadherin antibody on day 3 of
      pregnancy. The results showed that embryo implantation was significantly
      inhibited in the mice injected with 3 microg E-cadherin antibody. The mouse uteri
      in this group were collected on days 5, 6, and 7 of pregnancy and expressions of
      MMP-2 and -9 were studied. In situ hybridization and RT-PCR results showed that
      the expression of MMP-2 and -9 mRNAs in uteri of E-cadherin antibody treated
      group was increased on days 5-7. The results of gelatin zymography of MMPs showed
      that the activities of pro-MMP-2, MMP-2, and pro-MMP-9 were increased
      significantly on days 5 and 6, and pro-MMP-9 activity was increased on day 7. The
      present study suggested that E-cadherin was involved in embryo implantation
      through decreasing the expressions and activities of MMP-2 and -9.

PMID- 16564032
TI  - Peripheral and central distribution of TRPV1, substance P and CGRP of rat corneal
      neurons.
AB  - The rat corneal neurons expressing vanilloid receptor TRPV1, substance P (SP) and
      calcitonin-gene-related peptide (CGRP) were examined. In the cornea, some TRPV1
      immunoreactive nerve fibers displayed either SP- or CGRP immunoreactivity also.
      For observing corneal neuronal elements in the trigeminal ganglion (TG) and in
      the medulla oblongata, retrograde and anterograde cholera toxin subunit B (CTB)
      tracing methods combining with triple immunofluorescence technique were
      performed. The corneal neuronal somata were located in the ophthalmic division of
      the TG; 37% of them were immunoreactive for TRPV1. One third and three quarters
      of the corneal TRPV1-immunoreactive neurons co-expressed SP and CGRP,
      respectively. All of SP-immunoreactive corneal neurons exhibited TRPV1
      immunoreactivity. They were predominantly medium-sized (mean +/- SE = 638.2 +/-
      49.5 microm(2)) and significantly larger than SP-immunoreactive and TRPV1
      immunonegative neurons in the ophthalmic division of the TG. The central
      projection fibers of corneal neurons co-expressing TRPV1 with SP and CGRP were
      observed at the subnucleus interpolaris/caudalis transition within trigeminal
      nucleus. The present study suggests that TRPV1 of the corneal neurons works in
      close relation to SP and CGRP both in the cornea and CNS for healing and
      nociceptive transduction.

PMID- 16564033
TI  - Microglia induce neural cell death via a proximity-dependent mechanism involving
      nitric oxide.
AB  - Microglial cells play a major role in the pathogenesis of many neurological
      diseases by exacerbating neuronal and non-neuronal cell death, but the mechanisms
      involved are unclear. To investigate the microglial-neuronal interactions, we
      used the murine BV-2 microglial cell line and the human neuronal-like SK-N-SH
      neuroblastoma cell line in a co-culture system that enabled proximity-dependent
      interaction and communication, a trans-well system that allowed proximity
      independent communication through diffusible molecules only, and a conditioned
      media system through which no proximity-dependent interactions or cell-to-cell
      communication is possible. Activation of BV-2 cells with lipopolysaccharide and
      interferon-gamma (LPS/IFN-gamma) decreased viability of the BV-2 cells alone and
      in co-cultures with SK-N-SH cells, but not SK-N-SH cells grown alone. In
      contrast, activation of BV-2 cells in the trans-well and conditioned media system
      did not have any effect on the viability of SK-N-SH cells, suggesting that
      microglia must be in close proximity to the neural cells to elicit cytotoxicity.
      To determine the molecules involved in proximity-dependent cell death, inhibitors
      of microglial activation were investigated. Only the specific inducible nitric
      oxide synthase (iNOS) inhibitor S-methylisothiourea, and hypothermia, which is
      known to suppress microglial iNOS expression, prevented cell death after LPS/IFN
      gamma activation. These results suggest that activated microglia release nitric
      oxide that is, at least partially, responsible for proximity-dependent microglial
      mediated neural toxicity.

PMID- 16564034
TI  - Estrogen down-regulates glial activation in male mice following 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine intoxication.
AB  - Emerging evidence suggests beneficial effect of estrogen for Parkinson's disease
      (PD), yet the exact mechanisms implicated remain obscured. Activated glia
      observed in MPTP mouse model and in PD may participate in the cascade of
      deleterious events that ultimately leads to dopaminergic nigral neuronal death.
      In vitro studies demonstrate that estrogen can modify the microglial and
      astroglial expression of inflammatory mediator, such as cytokines and chemokines
      implicated in neuroinflammation and neurodegeneration. To determine whether
      estrogen-elicited neuroprotection in PD is mediated through glia, adult male
      C57Bl/6 mice were treated with 17beta-estradiol (E2) for a total of 11 days.
      Following 5 days of pretreatment with E2, they were injected with 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the sixth day. The brains were
      collected on day 11. Immunohistochemistry and quantitative study were used to
      assess the number of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the
      substantia nigra pars compacta (SNpc) and that of activated astrocytes and
      activated microglia in the SNpc and the striatum. Pretreatment with E2 decreased
      the loss of TH-IR nigral neurons and diminished the deficit of TH-IR striatal
      fibers triggered by MPTP. The neuroprotective effect of E2 was coincident with an
      attenuation of a glial response within the nigra and the striatum. These findings
      suggest that the neuroprotective effects of E2 evidenced in MPTP mouse model
      might mediate through an inhibition of reactive glia. However, direct
      neuroprotective effects of E2 upon TH-IR neurons cannot be excluded.

PMID- 16564035
TI  - Auditory processing disorder (APD)-potential contribution of mouse research.
AB  - APD is a common, heterogeneous and poorly understood listening impairment that is
      receiving increasing recognition, especially in children and the elderly. The
      primary symptom in humans is poor speech perception despite normal pure tone
      audiometry. Diagnostic practice is patchy, but current proposals are to
      distinguish APD by reduced ability to detect, discriminate, localize and order
      non-speech sounds. APD appears to result predominantly from core malfunctioning
      of the central auditory system, but with strong cognitive influences and possible
      additional influences from peripheral auditory and crossmodal sources. APD may be
      acquired (e.g. through middle ear disease), but it is likely that a more common
      etiology would involve both environmental and inherited contributions. Mice are
      increasingly being used for studies of central auditory processing. Most work to
      date has documented the basic response properties of auditory neurons, or used
      single gene mutations to investigate specific functions. For high throughput,
      primary screening, reflex and/or event-related potential measures are required.
      Pre-pulse inhibition (PPI), the regulation of an acoustic startle reflex by a
      preceding sound having distinct spatial, temporal or spectral properties, is one
      way in which auditory processing may be screened. For secondary assessment,
      standard psychoacoustic tests for mice have been developed.

PMID- 16564036
TI  - A simple and mild synthesis of a 4,5-cyclopropanated carbohydrate.
AB  - The synthesis of a 4,5-cyclopropanated carbohydrate was achieved in five steps
      from methyl alpha-D-mannopyranoside under mild conditions that avoid the use of
      carbene chemistry.

PMID- 16564037
TI  - Sequence determination of oligosaccharides and regular polysaccharides using NMR
      spectroscopy and a novel Web-based version of the computer program CASPER.
AB  - A WWW-interface to a program for structure elucidation of oligo- and
      polysaccharides using NMR data, CASPER, is presented. The interface and the
      underlying program have been extensively tested using published data and it was
      able to simulate 13C NMR spectra of >200 structures with an average error of
      about 0.3 ppm/resonance. When applied to the repeating units of Escherichia coli
      O-antigens the published structures were found among the five highest ranked
      structures in 75% of the cases. The average deviation between calculated and
      experimental 13C chemical shifts was 0.45 ppm. Oligosaccharide spectra were
      calculated with even better accuracy (0.23 ppm/resonance) and the correct
      structure was ranked 1st or 2nd in all the cases examined. Additional NMR
      experiments that may be required to distinguish between candidate structures are
      aided by the assignments provided by the program. This computational approach is
      also suitable for use in structural confirmation of chemically or enzymatically
      synthesized oligosaccharides. The program is found at
      http://www.casper.organ.su.se/casper.

PMID- 16564038
TI  - Structure of a complex of Thermoactinomyces vulgaris R-47 alpha-amylase 2 with
      maltohexaose demonstrates the important role of aromatic residues at the reducing
      end of the substrate binding cleft.
AB  - Thermoactinomyces vulgaris R-47 alpha-amylase 2 (TVAII) can efficiently hydrolyze
      both starch and cyclomaltooligosaccharides (cyclodextrins). The crystal structure
      of an inactive mutant TVAII in a complex with maltohexaose was determined at a
      resolution of 2.1A. TVAII adopts a dimeric structure to form two catalytic sites,
      where substrates are found to bind. At the catalytic site, there are many
      hydrogen bonds between the enzyme and substrate at the non-reducing end from the
      hydrolyzing site, but few hydrogen bonds at the reducing end, where two aromatic
      residues, Trp356 and Tyr45, make effective interactions with a substrate. Trp356
      drastically changes its side-chain conformation to achieve a strong stacking
      interaction with the substrate, and Tyr45 from another molecule forms a water
      mediated hydrogen bond with the substrate. Kinetic analysis of the wild-type and
      mutant enzymes in which Trp356 and/or Tyr45 were replaced with Ala suggested that
      Trp356 and Tyr45 are essential to the catalytic reaction of the enzyme, and that
      the formation of a dimeric structure is indispensable for TVAII to hydrolyze both
      starch and cyclodextrins.

PMID- 16564039
TI  - Antioxidant status and stress proteins in the gills of the brown mussel Perna
      perna exposed to zinc.
AB  - Zinc, at low levels, has several basic housekeeping functions in metalloenzymes,
      transcription factors, immunoregulation, growth, and cytoprotection, displaying
      antioxidant, anti-apoptotic, and anti-inflammatory roles. At high levels,
      however, the metal can be highly toxic. The aim of this work is to investigate
      the toxic effect of zinc on antioxidant status and stress proteins in the gills
      of the brown mussel Perna perna exposed for 48 h to zinc chloride (zinc) at 10,
      30 and 100 microM. Glutathione reductase (GR) activity was drastically reduced at
      30 and 100 microM zinc. At the lower levels, i.e. 10 microM zinc, antioxidant
      defenses were up-regulated, as were glutathione levels and the activities of
      glutathione peroxidase and catalase, in spite of the absence of effect on
      glutathione S-transferase and glucose 6-phosphate dehydrogenase activity. At the
      higher tested concentration of 100 microM zinc, oxidative stress was apparent as
      reflected by the increased lipid peroxidation end products and decreased protein
      thiol and glutathione levels, associated with an inability to up regulate
      antioxidant defenses. Using 30 microM zinc, higher gill rhodamine B efflux was
      observed, indicating an activation of multixenobiotic resistance (MXR) activity,
      which is reinforced by increased immunoreactive P-glycoprotein detection. Zinc
      also increased the HSP60-immunoreactive protein, whereas the HSP70-immunoreactive
      protein remained unchanged. Overall, the results indicate that zinc toxicity --
      at higher levels -- may be connected to a strong inhibition of GR activity, and
      related to the pro-oxidative state found. Mussels showed an adaptive-like
      response to 10 microM zinc by increasing antioxidant defenses. Increased P
      glycoprotein and HSP60 expression, and rhodamine B efflux were also remarkable
      features in the gill response to zinc.

PMID- 16564040
TI  - Synergistic interaction between Gdf1 and Nodal during anterior axis development.
AB  - Growth and Differentiation Factor 1 (GDF-1) has been implicated in left-right
      patterning of the mouse embryo but has no other known function. Here, we
      demonstrate a genetic interaction between Gdf1 and Nodal during anterior axis
      development. Gdf1-/-;Nodal+/- mutants displayed several abnormalities that were
      not present in either Gdf1-/- or Nodal+/- single mutants, including absence of
      notochord and prechordal plate, and malformation of the foregut; organizing
      centers implicated in the development of the anterior head and branchial arches,
      respectively. Consistent with these deficits, Gdf1-/-;Nodal+/- mutant embryos
      displayed a number of axial midline abnormalities, including holoprosencephaly,
      anterior head truncation, cleft lip, fused nasal cavity, and lack of jaws and
      tongue. The absence of these defects in single mutants indicated a synergistic
      interaction between Nodal and GDF-1 in the node, from which the axial mesendoderm
      that gives rise to the notochord, prechordal plate, and foregut endoderm
      originates, and where the two factors are co-expressed. This notion was supported
      by a severe downregulation of FoxA2 and goosecoid in the anterior primitive
      streak of double mutant embryos. Unlike that in the lateral plate mesoderm, Nodal
      expression in the node was independent of GDF-1, indicating that both factors act
      in parallel to control the development of mesendodermal precursors. Receptor
      reconstitution experiments indicated that GDF-1, like Nodal, can signal through
      the type I receptors ALK4 and ALK7. However, analysis of compound mutants
      indicated that ALK4, but not ALK7, was responsible for the effects of GDF-1 and
      Nodal during anterior axis development. These results indicate that GDF-1 and
      Nodal converge on ALK4 in the anterior primitive streak to control the formation
      of organizing centers that are necessary for normal forebrain and branchial arch
      development.

PMID- 16564042
TI  - Secretory phospholipase A2 induces apoptosis through TNF-alpha and cytochrome c
      mediated caspase cascade in murine macrophage RAW 264.7 cells.
AB  - Phospholipase A2 (PLA2) is an esterase that cleaves the sn-2 ester bond in
      glycerophospholipids, thereby releasing free fatty acids and lysophospholipids.
      In addition to the apoptotic activity of cytosolic PLA2 and Ca2+-independent
      PLA2, recent studies showed that secretory PLA2 (sPLA2) also play a role in
      apoptosis. However, the details of molecular mechanism have not been fully
      elucidated. Our data demonstrated that group IB PLA (IB PLA2)-exposed murine
      macrophage 264.7 cells showed characteristic features of apoptosis such as
      morphological changes, DNA laddering, staining positive for propidium iodide (PI)
      as well as Annexin V and activation of caspases and subsequent cleavage of poly
      (ADP-ribose) polymerase (PARP) in dose- and time-dependent manner. Moreover, IB
      PLA2 was found to elicit tumor necrosis factor (TNF)-alpha production and release
      of cytochrome c, suggesting that IB PLA2 exerts its apoptotic activity via the
      induction of TNF-alpha production and cytochrome c release, which results in
      triggering the activation of caspase cascade and PARP cleavage.

PMID- 16564041
TI  - Dexamethasone increases fluid absorption via Na+/H+ exchanger (NHE) 3 activation
      in normal human middle ear epithelial cells.
AB  - The proper homeostasis of the liquid lining the surface of the middle ear cavity
      is vitally important for maintaining a fluid-free middle ear cavity. Disruption
      of this homeostasis leads to fluid collection in the middle ear cavity and
      results in otitis media with effusion. We demonstrated the molecular and
      functional expression of the Na+/H+ exchanger (NHE)s in normal human middle ear
      epithelial (NHMEE) cells. We also evaluated the role of NHEs in fluid absorption
      and the effect of dexamethasone on NHE function and NHE-dependent fluid
      absorption in NHMEE cells. Western blot analysis was performed for NHE1, -2, and 
      3 in NHMEE cells. The fluid absorption rate was measured after liquid application
      on the luminal surface of the cells. Intracellular pH (pHi) was measured using
      the pH-sensitive fluorescent probe bis-(2-carboxyethyl)-5(6)-carboxyfluorescein
      (BCECF)-AM. NHE activity was determined as Na+-induced pHi recovery from an acid
      load achieved by luminal exposure to 40 mmol/l NH4Cl. NHE1, -2 and -3 were all
      expressed in the NHMEE cells. The pHi recovery rate was suppressed by inhibition
      of NHE2 and -3 with HOE694 at concentrations greater than 50 microM. Inhibition
      of NHE3 with 650 microM of HOE694 or S3226 significantly decreased the fluid
      absorption rate. Dexamethasone increased the Na+-induced pHi recovery rate which
      was reversed by the inhibition of NHE3 with 650 microM of HOE694. Dexamethasone
      treatment up-regulated NHE3 expression in a dose-dependent manner. The fluid
      absorption rate was increased by treatment with dexamethasone (10(-7) M) and
      reversed by the inhibition of NHE3. In summary, we have shown that NHE3 are
      involved in the regulation of both pHi and fluid absorption on the luminal
      surface of NHMEE cells. Dexamethasone stimulates NHE3 expression and NHE3
      dependent fluid absorption in NHMEE cells. These findings provide a new insight
      into mechanisms that regulate periciliary fluid and the therapeutic mechanisms
      behind steroid treatment of otitis media with effusion.

PMID- 16564043
TI  - Rho-dependent, Rho kinase-independent inhibitory regulation of Rac and cell
      migration by LPA1 receptor in Gi-inactivated CHO cells.
AB  - Lysophosphatidic acid (LPA) is a major serum lysophospholipid that stimulates
      cell migration in diverse cell types including ovarian cancer cells. We report
      here that in the absence of Gi function, LPA induces inhibition, rather than
      stimulation, of cellular Rac activity, lamellipodium formation, and cell
      migration in response to insulin like growth factor I (IGF-I) in Chinese hamster
      ovary (CHO) cells, which solely express LPA1 as a LPA receptor. The inhibitory
      effects of LPA are abrogated by the expression of either Galpha13 C-terminal
      peptide or C3 toxin pretreatment, but not a Rho kinase inhibitor. Without PTX
      pretreatment, LPA stimulates Rac and cell migration yet similarly activates Rho,
      indicating that Rho activation by itself is not sufficient for inhibition of cell
      migration. Conversely, the expression of a dominant negative Rac mutant
      sufficiently mimics the LPA inhibition of cell migration. LPA inhibits IGF I
      induced Akt activation by only 40% in a manner dependent on Rho kinase. These
      results demonstrate that inhibition of Gi function converts LPA regulation on Rac
      and cell migration to an inhibitory mode, which is mediated by G13 and Rho but
      not Rho kinase, and raise a possibility of Gi as a new therapeutic target for LPA
      dependent tumor progression.

PMID- 16564044
TI  - Krypton laser photocoagulation induces retinal vascular remodeling rather than
      choroidal neovascularization.
AB  - The purpose of this study is to analyze the retina and choroid response following
      krypton laser photocoagulation. Ninety-two C57BL6/Sev129 and 32 C57BL/6J, 5-6
      week-old mice received one single krypton (630 nm) laser lesion: 50 microm, 0.05
      s, 400 mW. On the following day, every day thereafter for 1 week and every 2-3
      days for the following 3 weeks, serial sections throughout the lesion were
      systematically collected and studied. Immunohistology using specific markers or
      antibodies for glial fibrillary acidic protein (GFAP) (astrocytes, glia and
      Muller's cells), von Willebrand (vW) (vascular endothelial cells), TUNEL (cells
      undergoing caspase dependent apoptosis), PCNA (proliferating cell nuclear
      antigen) p36, CD4 and F4/80 (infiltrating inflammatory and T cells), DAPI (cell
      nuclei) and routine histology were carried out. Laser confocal microscopy was
      also performed on flat mounts. Temporal and spatial observations of the created
      photocoagulation lesions demonstrate that, after a few hours, activated glial
      cells within the retinal path of the laser beam express GFAP. After 48 h, GFAP
      positive staining was also detected within the choroid lesion center. "Movement"
      of this GFAP-positive expression towards the lasered choroid was preceded by a
      well-demarcated and localized apoptosis of the retina outer nuclear layer cells
      within the laser beam path. Later, death of retinal outer nuclear cells and layer
      thinning at this site was followed by evagination of the inner nuclear retinal
      layer. Funneling of the entire inner nuclear and the thinned outer nuclear layers
      into the choroid lesion center was accompanied by "dragging" of the retinal
      capillaries. Thus, from days 10 to 14 after krypton laser photocoagulation
      onward, well-formed blood capillaries (of retinal origin) were observed within
      the lesion. Only a few of the vW-positive capillary endothelial cells stained
      also for PCNA p36. In the choroid, dilatation of the vascular bed occurred at the
      vicinity of the photocoagulation site and around it. Confocal microscopy
      demonstrates that the vessels throughout the path lesion are located within the
      neuroretina while in the choroid (after separation of the neural retina) only
      GFAP-positive but no lectin-positive cells can be seen. The involvement of
      infiltrating inflammatory cells in these remodeling and healing processes
      remained minimal throughout the study period. During the 4 weeks following
      krypton laser photocoagulation in the mouse eye, processes of wound healing and
      remodeling appear to be driven by cells (and vessels) originating from the
      retina.

PMID- 16564045
TI  - Predictability and limitations of non-invasive murine tonometry: comparison of
      two devices.
AB  - Our purpose was to evaluate the accuracy, reproducibility and predictive ability
      of two non-invasive tonometers developed for intraocular pressure (IOP)
      measurements in the mouse. The prototype impact-rebound tonometer (I-R) and a
      prototype optical interferometry tonometer (OIT) utilizing a fiberoptic pressure
      sensor, were compared. Enucleated eyes from C57/BL6 mice were used for the
      calibration. The anterior chamber was cannulated and the IOP was adjusted in
      increments of 5 cm of H2O (open stopcock method). A calibration curve was
      generated for each individual eye along with a master calibration curve for all
      eyes. Two operators measured the IOP. The instruments were then used in
      alternating order to measure the IOP in C57/BL6 and in DBA2/J animals. The same
      eyes were subsequently cannulated and the error of the non-invasive tonometers
      was determined. Both tonometers yielded almost equivalent ex vivo calibration
      curves with individual R2 of 0.9878 and 0.9902 respectively. Both instruments
      were highly reproducible. In vivo the I-R tonometer underestimated while the OIT
      overestimated the IOP. This error was systematic and therefore predictable. The
      confidence intervals of this error were determined by comparing the IOP estimates
      provided by each tonometer with the measurements obtained invasively by
      cannulation in vivo. The 95% CI of the error were 2.36 mmHg for the I-R and 2.62
      mmHg for the OIT respectively. Non-invasive tonometry in the mouse is feasible.
      Both non-invasive instruments provide accurate and reproducible measurements with
      the OIT requiring calibration curves for each individual investigator.

PMID- 16564046
TI  - Effect of the exposure to Fasciola hepatica (Trematoda: Digenea) on life history
      traits of Lymnaea cousini and Lymnaea columella (Gastropoda: Lymnaeidae).
AB  - The snails Lymnaea columella and Lymnaea cousini have both been reported as
      intermediate hosts of Fasciola hepatica in Colombia. The effect of the exposure
      to the parasite on survival, fecundity and size of these snails was evaluated by
      means of experimental infections and the life history traits of control and
      exposed groups were compared. Infection rates were 82.2 and 34% for L. columella
      and L. cousini, respectively. A reduction in fitness was observed in both species
      when exposed to the parasite: fecundity alone was reduced in L. columella whereas
      in L. cousini there was also a decline in survival rate. Unlike other studies,
      increased size was not observed in either species. On the contrary, a reduction
      in growth rate was observed in L. columella.

PMID- 16564048
TI  - Mice convert melatonin to 6-sulphatoxymelatonin.
AB  - The principal objective of this study was to establish whether mice can convert
      melatonin to 6-sulphatoxymelatonin (aMT6s). Precision-cut liver slices from
      C3H/He, C57BL/6, and BALB/c mice were incubated with melatonin, and the
      concentration of aMT6s in the culture media was determined using a sensitive and
      specific radioimmunoassay procedure. All three strains of mice generated aMT6s in
      a time-dependent manner; no significant strain differences were observed. When
      samples of the media were treated with sulphatase prior to analysis, aMT6s was
      not detectable. In contrast, similar treatment with beta-glucuronidase had no
      effect. 6-Sulphatoxymelatonin was present in the urine of both control and
      melatonin-treated C3H/He and C57BL6 mice. Treatment with melatonin led to a
      dramatic rise in the urinary levels of aMT6s in both mouse strains. Pre-treatment
      of the urines with sulphatase, but not beta-glucuronidase, markedly decreased the
      levels of aMT6s. Finally, in both strains urinary excretion of aMT6s displayed
      diurnal rhythmicity, peak excretion occurring during the dark hours. It may be
      inferred that: (a) mice can convert melatonin to aMT6s, both in vivo and in
      vitro, and (b) mice generate aMT6s in a rhythmic manner. Finally, the present
      studies confirm that determination of aMT6s rhythms in mice could provide an
      alternative, non-invasive, approach for assessing circadian clock function.

PMID- 16564049
TI  - Natural and gonadotropin-induced ovarian activity in tigers (Panthera tigris)
      assessed by fecal steroid analyses.
AB  - Fecal samples were collected from female tigers (n = 17) to compare endocrine
      patterns associated with natural ovarian activity with those after chorionic
      gonadotropin ovulation induction and artificial insemination (AI). Baseline fecal
      estradiol concentrations were 65.77 +/- 3.61 ng/g with estrual peaks of 167.39 +/
      9.92 ng/g and an anovulatory cycle length of 17.96 +/- 0.70 days. Peak fecal
      estradiol was higher when females were housed with a male for breeding (262.30 +/
      41.43 vs. 165.30 +/- 3.67 ng/g; P < 0.05). The majority of animals showed some
      seasonal differences in fecal estradiol however, patterns were inconsistent.
      Fecal progestagens increased only after breeding confirming tigers are primarily
      induced ovulators. The non-pregnant luteal phase was 34.50 +/- 1.85 days in
      duration. In pregnant tigers, fecal progestagens remained elevated for 108 days
      until parturition and the diagnosis of pregnancy was possible based on the
      elevated fecal progestagens after 35 days of gestation. Tigers were administered
      equine chorionic gonadotropin (eCG) to stimulate follicular growth and human
      chorionic gonadotropin (hCG) to induce ovulation prior to AI [200 IU eCG/100 IU
      hCG (n = 5); 400 IU eCG/200 IU hCG (n = 2); 500 IU eCG/100 IU hCG (n = 2); 1000
      IU eCG/750 IU hCG (n = 11); 1000 IU eCG/1000 IU hCG (n = 4)]. None of the tigers
      subjected to AI became pregnant (n = 9). Fecal endocrine patterns in gonadotropin
      stimulated tigers were considerably different from those observed in naturally
      bred tigers. In particular, fecal estradiol concentrations were higher than those
      observed during natural estrus and remained elevated for longer periods of time
      in tigers administered the higher doses of gonadotropins typically used in
      conjunction with AI in this species. These abnormal endocrine patterns may help
      explain the poor success rate of AI in this species.

PMID- 16564050
TI  - Live twin tubal ectopic pregnancy.

PMID- 16564051
TI  - Stress-relaxation and microscopic dynamics of rabbit periodontal ligament.
AB  - The aim of the present study was to examine the structural basis for the stress
      relaxation behaviour of the periodontal ligament (PDL). Seventeen 4-month-old
      rabbits were used. A tooth-PDL-bone segment was cut in a rectangular prism from
      the incisor of a dissected mandible. The specimen was mounted in a testing
      machine built on a video stereomicroscope. Following preconditioning, each
      specimen was stretched to a deformation of 35 microm and then the deformation was
      kept constant for 300 s to obtain a stress-relaxation curve. Thereafter, stress
      relaxation tests were repeated sequentially at deformations of 55, 75, and 95
      microm. Polarised-light video-stereomicroscopic images of the specimens were
      simultaneously recorded and analysed with the stress-relaxation curves. The image
      analysis revealed that during stress-relaxation, the brightness of the
      birefringent fibres tended to initially increase rapidly and then do so
      gradually. There were negative correlations between the brightness and relaxation
      modulus at the four deformations. The decreases of normalised relaxation modulus
      for 300 s were less at greater deformation levels. The stress-relaxation process
      was well described by a function with three exponential decay terms and a
      constant. These findings suggest that during stress-relaxation of the PDL, the
      alignment of the collagen molecules and fibrils within the stretched fibres may
      occur, which could be driven by the strain energy imparted to the specimen on
      initial stretching.

PMID- 16564052
TI  - Suitability of tandem-in-time mass spectrometry for polybrominated diphenylether
      measurement in fish and shellfish samples: comparison with high resolution mass
      spectrometry.
AB  - The first part of the present study focused on the development of an alternative
      automated sample preparation method for the measurement of selected
      polybrominated diphenyl ethers (PBDEs) in fish and shellfish. A previously
      developed automated method has been further optimized and simplified to decrease
      blank levels and cost. Sorbent and solvent quantities have been significantly
      reduced without altering extract quality. The second part of the study consisted
      of comparing tandem-in-time quadrupole ion storage mass spectrometry (QISTMS/MS)
      to high resolution mass spectrometry (HRMS) for the isotope dilution (ID)
      measurement step after gas chromatography (GC) separation. Both mass
      spectrometric methods performed similarly in terms of accuracy but better
      precision was observed for HRMS. Although better sensitivity can be attained with
      the high resolution sector instrument, method limits of quantification (mLOQs)
      were very similar for both approaches as they were dependent on the procedural
      blanks levels. The mLOQ values ranged between 0.04 and 3.56 ng/g fat, depending
      on the congener. They allowed the unambiguous identification and quantification
      of all target analytes, except for BDE-183, in most considered fish extracts. An
      analytical procedure based on rapid automated sample preparation and QISTMS/MS
      appeared to be suitable for the measurement of PBDEs in fish and shellfish
      speciment under quality assurance/quality control (QA/QC) criteria.

PMID- 16564053
TI  - Fully dilutable microemulsions embedded with phospholipids and stabilized by
      short-chain organic acids and polyols.
AB  - Evidence on the role of phosphatidylcholine (PC) as a membrane permeability
      enhancer was the driving force in forming new liquid nanosized (modified
      microemulsions) oral delivery system containing PC molecules. In this study we
      have demonstrated the feasibility of constructing phase diagrams with a large
      isotropic regions capable of being fully diluted with water. The microemulsions
      were stabilized with mixtures composed of PC and nonionic surfactant
      (polyoxyethylene-40 hydrogenated castor oil, HECO40) and short-chain organic acid
      as cosurfactant/cosolvent. When propionic acid served as the
      cosurfactant/cosolvent, the isotropic region was at its maximum (ca. 72% of the
      total phase diagram area). The presence of a blend of PC and HECO40 seems to have
      synergistic effects, forming an isotropic region comprising 72% of the area of
      the phase diagram, in comparison to 20 and 50% in systems stabilized by PC and
      HECO40, alone, respectively. The role of the PC molecules in the formation of
      those microemulsions is demonstrated by comparing three soy lecithins. Lecithin
      with a high PC content forms larger isotropic regions with more "free dilution"
      lines. Several nonionic surfactants have been investigated, yet only HECO40 seems
      to have a packing parameter suitable for the formation of large isotropic U-type
      systems.

PMID- 16564054
TI  - Professionalism and functional outcomes.
AB  - A foundation principle of professionalism is listening carefully to clients'
      needs. This paper reviews current studies that have sought to listen to the needs
      of people with aphasia and their families. The preliminary evidence to date
      suggests that people with aphasia have goals that cover the bio-psycho-social
      spectrum but place a lot of importance on functional outcomes such as
      participation in life's activities, relationships, and personal self-esteem. In
      contrast, descriptions of current aphasia management practices reflect a
      predominantly medical model approach that emphasizes impairment-level goals. This
      paper suggests that a proportion of speech-language pathologists are not truly
      listening and responding to their clients' needs. This leads to a mismatch
      between the therapists' and clients' goals in therapy. The concept of person
      centred goal-setting is described. This may contribute to greater alignments of
      goals and better outcomes of rehabilitation. LEARNING OUTCOMES: As a result of
      reading this work, the participant will be able to: (a) have knowledge of
      criticisms of aphasia therapy by people with aphasia; (b) understand the concept
      of person-centred goal-setting; (c) understand the complexity of mismatched goals
      between therapist and client.

PMID- 16564055
TI  - Development of a quantitative cell-based ELISA, for a humanized anti-IL-2/IL-15
      receptor beta antibody (HuMikbeta(1)), and correlation with functional activity
      using an antigen-transfected murine cell line.
AB  - The HuMikbeta(1), a humanized IgG1 monoclonal antibody directed toward the IL
      2/IL-15 receptor beta-chain (CD122), inhibits the actions of the inflammatory
      cytokine IL-15, and may be useful for immunotherapy of an array of autoimmune
      disorders as well as diseases associated with the retrovirus human T-cell
      lymphotrophic virus 1 (HTLV-1). In order to facilitate the production of material
      for clinical investigation, we developed a cell-based ELISA (CbELISA) for
      measuring the binding activity, as a potential biological activity marker, of the
      HuMikbeta(1) monoclonal antibody to a transfected 32D mouse cell line (32Dbeta)
      expressing IL-2Rbeta antigen on the cell surface. There is specific binding of
      HuMikbeta(1) to the transfected cell line, titrating out in the concentration
      range of 1-1,000 ng/ml. Under identical conditions, there was no binding of
      HuMikbeta(1) to the parent cell line 32D. Satisfactory binding curves with
      HuMikbeta(1) were obtained with 32Dbeta cells grown between 3 and 19 passages in
      culture and at seed densities of 2 x 10(5)-4 x 10(6) cells/well. The binding was
      specific for Mikbeta antibodies recognizing the IL-2/IL-15 receptor beta subunit
      as demonstrated by binding of HuMikbeta(1), Mikbeta(2) and Mikbeta(3) antibodies,
      and lack of binding of irrelevant humanized and chimeric antibodies and isotype
      matched human IgG1 to the 32Dbeta cell. Also, the human IgG1 and irrelevant
      humanized and chimeric antibodies did not interfere with the HuMikbeta(1)
      binding. The assay could detect changes in binding activity of HuMikbeta(1)
      antibody under stressful conditions (heat and low pH) and the results paralleled
      the effect of stress on the physicochemical characteristics. More importantly,
      the binding activity shows an apparent correlation to inhibition of IL-15-induced
      proliferation of 32Dbeta cells with HuMikbeta(1). In conclusion, the cell-based
      ELISA method represents a simple, reproducible accurate quantitative assay for
      monitoring HuMikbeta(1) activity and could be used as a potency marker assay for
      monitoring the lot-lot consistency and functional stability of HuMikbeta(1)
      product.

PMID- 16564056
TI  - Effects of Ser16 phosphorylation on the allosteric transitions of
      phospholamban/Ca(2+)-ATPase complex.
AB  - Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase
      1 modulate the inhibitory activity of phospholamban (PLN), the endogenous
      regulator of the sarco(endo)plasmic reticulum calcium Ca(2+) ATPase (SERCA). This
      cyclic mechanism constitutes the driving force for calcium reuptake from the
      cytoplasm into the myocite lumen, regulating cardiac contractility. PLN undergoes
      a conformational transition between a relaxed (R) and tense (T) state, an
      equilibrium perturbed by the addition of SERCA. Here, we show that the single
      phosphoryl transfer at Ser16 induces a more pronounced conformational switch to
      the R state in phosphorylated PLN (pPLN). The binding affinity of PLN to SERCA is
      not affected (K(d) values for the transmembrane domains of pPLN and PLN are
      approximately 60 microM), supporting the hypothesis that phosphorylation at Ser16
      does not dissociate PLN from SERCA. However, the binding surface and dynamics in
      domain Ib (residues 22-31) change substantially upon phosphorylation. Since PLN
      can be singly or doubly phosphorylated at Ser16 and Thr17, we propose that these
      sites remotely control the conformation of domain Ib. These findings constitute a
      paradigm for how post-translational modifications such as phosphorylation in the
      cytoplasmic portion of membrane proteins control intramembrane protein-protein
      interactions.

PMID- 16564057
TI  - Long-term antipsychotic treatments and crossover studies in rats: differential
      effects of typical and atypical agents on the expression of antioxidant enzymes
      and membrane lipid peroxidation in rat brain.
AB  - Short-term (<45 days) treatment studies in rats have reported increased oxidative
      stress and oxidative (i.e., oxygen free radical-mediated) neural cell injury with
      typical antipsychotics such as haloperidol, but not with the atypicals such as
      clozapine, olanzapine or risperidone. However, now these and several other
      atypical antipsychotics that differ in their neurotransmitter receptor affinity
      profiles are being used for a long-term treatment of schizophrenia. Therefore,
      understanding of their long-term treatment effects on the expression of
      antioxidant enzymes and oxidative neural cell injury in rats may be important to
      explain the possible differential mechanisms underlying their long-term clinical
      and side effects profiles. The effect of 90 and 180 day exposure to haloperidol
      (HAL, 2mg/kg/day), a representative typical antipsychotic was compared to
      exposure to chlorpromazine (CPZ, 10mg/kg/day), ziprasidone (ZIP, 12mg/kg/day),
      risperidone (RISP, 2.5mg/kg/day), clozapine (CLOZ, 20mg/kg/day) or olanzapine
      (OLZ, 10mg/kg/day) on the expression of antioxidant defense enzymes and levels of
      lipid peroxidation in the rat brain. The drug-induced effects on various
      antioxidant defense enzymes; manganese-superoxide dismutase (MnSOD), copper-zinc
      superoxide dismutase (CuZnSOD) and catalase (CAT) were assessed by determination
      of their enzymatic activity and protein content. Immunohistochemical analysis was
      also carried out to assess the cellular levels of MnSOD and CuZnSOD and cellular
      morphology. The oxidative membrane damage was assessed by determination of levels
      of the lipid peroxidation product, hydroxyalkanals (HAEs) in the rat brain. Both
      90 and 180 days of HAL treatment very significantly decreased the levels of MnSOD
      (50%) and CuZnSOD (80%) and increased the levels of HAEs compared to vehicle
      treatment. Smaller reduction was found in CAT (25%) and no change in the
      glutathione peroxidase (GSHPx). The levels of enzymatic activity correlated
      generally well with the levels of enzyme protein indicating that the changes were
      in the expression of net protein. Though atypical antipsychotics like ZIP, RISP
      and OLZ did not show any change in the HAEs levels up to 90 days, further
      treatment up to 180 days resulted in significantly increased levels of HAEs in
      CPZ, ZIP and RISP, but not in OLZ treated rats. Post-treatment with several
      atypical antipsychotics (OLZ=CLOZ>RISP) for 90 days after 90 day of HAL treatment
      significantly restored the HAL-induced loss in MnSOD and CuZnSOD activities and
      increase in lipid peroxidation products as well as cellular morphology. These
      data may be very helpful in planning long-term use as well as switch over of
      these antipsychotics for the management of schizophrenia.

PMID- 16564058
TI  - High frequency of open-angle glaucoma in Japanese patients with Alzheimer's
      disease.
AB  - The clinical and genetic relationships between Alzheimer's disease (AD) and
      glaucoma remain obscure. The aim of this study was to determine the prevalence of
      open-angle glaucoma (OAG) in patients with AD and whether the apolipoprotein E
      (APOE) 4 allele is associated with AD, with or without OAG, in Japanese. The
      groups consisted of 172 patients with the diagnostic criteria of AD and 176 age
      matched controls. Ophthalmic examinations were conducted, and genomic analysis
      was performed by PCR and digestion of products with an enzyme. OAG was found in
      41 (23.8%) of the AD patients, which was a significantly (p = 0.0002) higher
      prevalence than that in the controls (9.9%). Furthermore, there was no
      significant difference between intraocular pressures (IOPs) in AD patients with
      OAG and without OAG. The percentage of AD patients who carried an APOE epsilon4
      allele (29.5%) was significantly (p = 0.0007) higher than that of the controls
      (9.1%). However, the percentage of AD patients with OAG who carried an APOE
      epsilon4 allele (35.7%) was not significantly different than that of AD patients
      without OAG (27.7%, p = 0.42). In summary, the prevalence of OAG is high in
      Japanese patients with AD, suggesting that common factors other than APOE may
      contribute to the two diseases.

PMID- 16564059
TI  - Homologous recombination is involved in repair of chromium-induced DNA damage in
      mammalian cells.
AB  - Chromium is a potent human carcinogen, probably because of its well-documented
      genotoxic effects. Chromate (Cr[VI]) causes a wide range of DNA lesions,
      including DNA crosslinks and strand breaks, presumably due to the direct and
      indirect effects of DNA oxidation. Homologous recombination repair (HRR) is
      important for error-free repair of lesions occurring at replication forks. Here,
      we show that HR deficient cell lines irs1SF and V-C8, deficient in XRCC3 and
      BRCA2, respectively, are hypersensitive to Cr[VI], implicating this repair
      pathway in repair of Cr[VI] damage. Furthermore, we find that Cr[VI] causes DNA
      double-strand breaks and triggers both Rad51 foci formation and induction of HRR.
      Collectively, these data suggest that HRR is important in repair of Cr[VI]
      induced DNA damage. In addition, we find that ERCC1, XRCC1 and DNA-PKcs defective
      cells are hypersensitive to Cr[VI], indicating that several repair pathways
      cooperate in repairing Cr[VI]-induced DNA damage.

PMID- 16564060
TI  - Toxin profile of Alexandrium ostenfeldii (Dinophyceae) from the Northern Adriatic
      Sea revealed by liquid chromatography-mass spectrometry.
AB  - This paper reports on the first occurrence of fairly high numbers of Alexandrium
      ostenfeldii along the Emilia Romagna coasts (Italy). Detailed liquid
      chromatography-mass spectrometry (LC-MS) analyses of the toxin profile were
      performed on a strain of the organism collected in November 2003, isolated during
      the event and grown in culture. Selected ion monitoring (SIM) and multiple
      reaction monitoring (MRM) experiments were carried out for detection of
      spirolides and paralytic shellfish poisoning (PSP) toxins. They revealed that the
      Adriatic A. ostenfeldii produces mainly spirolide 13-desmethyl C at levels of 3.7
      pg/cell but not PSP toxins. Interestingly, low levels of some spirolide isomers
      that have not been reported so far in other strains of the dinoflagellate were
      also detected. This represents the first report of spirolide-type toxins in the
      Adriatic Sea.

PMID- 16564061
TI  - Panther cap Amanita pantherina poisoning case report and review.
AB  - An analysis of patients with mushroom poisoning hospitalized in the Clinic of
      Toxicology in Cracow revealed that only a small percentage of cases had been
      caused by the death cap Amanita phalloides (Vaill. ex Fr.) Secr. The most
      important factors contributing to intoxication are confusion of toxic mushrooms
      with edible species, and non-specific mushroom poisoning. The genus Amanita has a
      global distribution and is one of the most well-known genera of macrofungi.
      Active toxins present in the panther cap (A. pantherina) (DC ex Fr.) Secr are
      ibotenic acid and muscimol, which are rapidly absorbed from the gastrointestinal
      tract. It is likely that other substances also participate in the psychotropic
      effects. Five frayed panther cap fruiting bodies were eaten by mistake by two
      persons (27 and 47 years of age). Symptoms onset occurred after 120 min with
      central nervous system (CNS) depression, ataxia, waxing and waning obtundation,
      religious hallucinations and hyperkinetic behaviour. In the present case,
      successful general symptomatic treatment was administered, which consisted of
      controlling the nervous symptoms and stabilizing the electrolyte balance. The
      poisoning regressed with no organ complications.

PMID- 16564062
TI  - Microcystin production in benthic mats of cyanobacteria in the Nile River and
      irrigation canals, Egypt.
AB  - The present study describes for the first time the species composition and
      toxicity of benthic cyanobacteria forming mats on the Nile River and irrigation
      canal sediments in Egypt. A total of 19 species of cyanobacteria were isolated
      from these mats during this study. The toxicity of the extracts of these species
      was investigated using Artemia salina assay, mouse bioassay and enzyme linked
      immunosorbent assay (ELISA). The results showed that all the 19 benthic species
      isolated from cyanobacterial mats, were toxic to A. salina. Two of these species,
      namely Calothrix parietina and Phormidium tenue, caused toxicity to mice with
      neurotoxic signs appeared within 12 h after injection. Whereas, five species
      showed hepatotoxic effects to mice within 6 h after injection. The results of
      ELISA showed that all the extracts which had hepatotoxic effects to mice,
      contained high levels of microcystins with concentrations ranging from 1.6 to 4.1
      mg g(-1) dry weight. HPLC analysis for heptotoxic extracts revealed that these
      extracts contained two peaks corresponding to microcystin-YR and -LR with
      different proportions. This study suggests that benthic species should be
      considered along with planktonic species during monitoring of toxic cyanobacteria
      in water sources, particularly the Nile river which is the main source of
      drinking water in Egypt.

PMID- 16564063
TI  - Importance of jararhagin disintegrin-like and cysteine-rich domains in the early
      events of local inflammatory response.
AB  - Jararhagin is a multi-domain SVMP from Bothrops jararaca venom comprising
      catalytic, disintegrin-like and cysteine-rich domains, which cause a local
      reaction manifested by hemorrhage, edema, cytokine release and inflammatory cell
      recruitment. In this study, the importance of disintegrin-like/cysteine-rich
      domains of jararhagin was addressed by analyzing the effects of jararhagin-C,
      which lacks the catalytic domain, in induction of leukocyte rolling and release
      of pro-inflammatory cytokines. Jararhagin-C was isolated from B. jararaca venom
      conserving the same ability of complete jararhagin molecule in inhibiting
      collagen-induced platelet-aggregation. Treatment of trans-illuminated cremaster
      muscle in vivo with jararhagin-C increased number of rolling leukocytes
      (approximately 250%) in post-capillary venules in all periods analyzed, without
      interfering with microvasculature haemodynamic, like vessel diameter, the
      erythrocyte speed or the blood flow rate. The release of pro-inflammatory
      cytokines TNF-alpha, IL-1beta and IL-6 was significantly enhanced in the local of
      jararhagin-C injection, showing the maximum levels in periods between 2 and 4 h
      after treatment. Besides the action of jararhagin-C, the presence of the
      inactivated catalytic domain in o-phenanthrolin-treated jararhagin was related to
      a higher increase in the number of rolling leukocytes. Moreover, the levels of IL
      6 and IL-1beta induced by catalytically active jararhagin were higher than those
      induced by jararhagin-C. In conclusion, our findings suggest that the disintegrin
      like/cysteine-rich domains of jararhagin are sufficient to locally activate the
      early events of an acute inflammatory response as leukocyte rolling and pro
      inflammatory cytokine release and this action may add to the effect of catalysis,
      which enhances the primary cell activation.

PMID- 16564064
TI  - Influence of intracellular toxin concentrations on cylindrospermopsin
      bioaccumulation in a freshwater gastropod (Melanoides tuberculata).
AB  - Scant information is available regarding the bioaccumulation of
      cylindrospermopsin (CYN) in aquatic organisms, particularly in invertebrates.
      This study examined toxin bioconcentration and bioaccumulation in the aquatic
      snail, Melanoides tuberculata, following exposure to freeze-thawed whole cell
      extracts and a live Cylindrospermopsis raciborskii culture containing CYN. Both
      bioconcentration and bioaccumulation were evident, but exposure to toxin in the
      freeze-thawed solutions resulted in minor tissue contamination compared with that
      resulting from live C. raciborskii exposure. Thus, whilst CYN uptake resulted
      from both extracellular and intracellular exposures, the availability of
      intracellular toxin was critical in affecting tissue CYN values. M. tuberculata
      did not bioconcentrate CYN into the shell. Bioaccumulation of the analog deoxy
      CYN was also recorded. Knowledge of intracellular toxin concentrations may be
      critical in evaluating the bioaccumulation, ecological and human health risks
      associated with contaminated systems.

PMID- 16564065
TI  - Biological and biochemical properties of the Brazilian Potamotrygon stingrays:
      Potamotrygon cf. scobina and Potamotrygon gr. orbignyi.
AB  - Stingrays of the family Potamotrygonidae are widespread throughout river systems
      of South America that drain into the Atlantic Ocean. Some species are endemic to
      the most extreme freshwater environment of the Brazil and cause frequent
      accidents to humans. The envenomation causes immediate, local, and intense pain,
      soft tissue edema, and a variable extent of bleeding. The present study was
      carried out in order to describe the principal biological and some biochemical
      properties of the Brazilian Potamotrygon fish venoms (Potamotrygon cf. scobina
      and P. gr. orbignyi). Both stingray venoms induced significant edematogenic and
      nociceptive responses in mice. Edematogenic and nociceptive responses were
      reduced when the venom was incubated at 37 or 56 degrees C. The results showed
      striking augments of leukocytes rolling and adherent cells to the endothelium of
      cremaster mice induced by both venoms. The data also presented that injection of
      both venoms induced necrosis, low level of proteolytic activity, without inducing
      haemorrhage. But when the venoms of both stingray species were injected together
      with their mucus secretion, the necrotizing activity was more vigorous. The
      present study provided in vivo evidence of toxic effects for P. cf. scobina and
      P. gr. orbignyi venoms.

PMID- 16564066
TI  - Imaging polarimetry of the circularly polarizing cuticle of scarab beetles
      (Coleoptera: Rutelidae, Cetoniidae).
AB  - The light reflected from the metallic-shiny regions of the cuticle of certain
      beetles belonging to the Scarabaeoidea is known since 1911 to be left-handed
      circularly polarized. Only photographs of a few selected species of scarabs,
      taken through left- and right-circular polarizers, have earlier been published.
      Through a right-circular polarizer these beetles appear more or less dark. This
      demonstration is, however, inadequate to quantitatively investigate the spatial
      distribution and the wavelength dependency of the circular polarization of light
      reflected from the scarab cuticle. In order to overcome this problem, we have
      developed a portable, rotating analyzer, linear/circular, digital, and imaging
      polarimeter. We describe here our polarimetric technique and present for the
      first time the linear and circular polarization patterns of the scarab species
      Chrysophora chrysochlora, Plusiotis resplendens (Rutelidae), and Cetonischema
      jousselini (Cetoniidae) in the red (650 nm), green (550 nm), and blue (450 nm)
      parts of the spectrum. We found the wavelength- and species-dependent circular
      polarization patterns in scarabs to be of a rather complex nature. These patterns
      are worthy of further studies.

PMID- 16564067
TI  - Visual fields and eye movements in a harbor seal (Phoca vitulina).
AB  - The boundaries of the visual fields of a harbor seal were measured using static
      perimetry. In the seal lying on a plane surface (fixation point "0 degrees"
      straight ahead at eye-level), the visual field with fixed eyes extended over 208
      degrees horizontally and reached from -12 degrees to +69 degrees vertically. The
      binocular visual field amounted to 67 degrees. Eye movements of 12 degrees (+/-2)
      degrees to both sides and 64 degrees upwards could be induced. In the seal
      performing eye movements, a visual field of 210 degrees in the horizontal plane
      and 121 degrees to the dorsal side was determined. From the measured eye
      movements, a visual field of 232 degrees in the horizontal plane appears
      possible.

PMID- 16564069
TI  - Carbon and nitrogen composition and stable isotope as potential indicators of
      source and fate of organic matter in the salt marsh of the Changjiang Estuary,
      China.
AB  - Elemental (TOC, TN, C/N) and stable carbon and nitrogen isotopic (delta(13)C,
      delta(15)N) compositions were measured for surface sediments, three sediment
      vibrocores, plants, and suspended particulate matter (SPM) collected from salt
      marsh of the Changjiang Estuary. The purpose of this study is to characterize the
      sources of organic matter in sediments and to further elucidate the factors
      influencing the isotope signature in the salt marsh. Our results indicate that
      organic matter preserved in the sediments is predominantly controlled by the
      particulate organic matter in the Changjiang Estuary. The in situ contribution of
      marsh plants carbon to sediment organic matter is clearest in the high marsh,
      where the low delta(13)C of the plants (-28.1 per thousand) is reflected by a
      sediment delta(13)C (-24.7 per thousand) lower than values found for the low
      marsh and bare flat sediments (-23.4 per thousand and -23.0 per thousand,
      respectively). The effect of grain size on the spatial difference of isotope
      composition in the marsh sediments is insignificant, based on the observation
      that similar isotope values are found in different size particles, both for
      delta(13)C and delta(15)N. Nutrient utilization by plant assimilation, however,
      shows great impact on the surface sediment delta(15)N composition, due to the
      isotope fractionation. With extensive plant coverage and the consequent low
      surface water nitrate concentration, delta(15)N values of the high marsh surface
      sediments show (15)N enrichment.

PMID- 16564068
TI  - Behavioral spectral sensitivity of the zebrafish (Danio rerio).
AB  - While the zebrafish (Danio rerio) continues to become an important animal model
      for the investigation of the genetic and physiological bases of visual processing
      of the vertebrate retina, its visual behavior, particularly regarding color
      processing, has received little attention. The purpose of this study was to
      obtain behavioral spectral sensitivity functions from adult zebrafish using an
      appetitive instrumental conditioning procedure. A three-chamber maze was
      implemented to train light-adapted adult zebrafish to swim into the chamber that
      contained a suprathreshold monochromatic stimulus for a food reward. Visual
      threshold was determined by varying the stimulus irradiance using a 'two-down one
      up' staircase procedure. Threshold values were obtained for wavelengths from 340
      to 640 nm. Spectral sensitivity functions obtained show contributions from two
      nonopponent cone mechanisms (UV and S) and two opponent mechanisms (M-S and L-M).
      These cone mechanisms are qualitatively similar to those obtained via
      physiological measures from the On-responses of the zebrafish retina and optic
      tectum. However, the functions are not quantitatively similar suggesting that
      further visual processing takes place beyond the processing of the retinal
      circuitry and processing of the initial stages of the optic tectum. These results
      demonstrate that the zebrafish is an excellent model to examine and compare the
      relationship between physiological and behavioral color processing.

PMID- 16564070
TI  - Surveillance programme on dioxin levels in soils in the Campo de Gibraltar
      (southwest Spain).
AB  - The results of an epidemiologic study undertaken by the Spanish Council for
      Scientific Research (CSIC) after commission by the Spanish Parliament indicated
      that Huelva and Cadiz were the zones in Andalusia with elevated risk of cancer. A
      6% (women) and 10% (men) cancer mortality excess was observed with respect to the
      other six Andalusian provinces. Huelva and Cadiz are located in the south-western
      region of Spain, and are characterized by a strong industrial activity
      concentrated in several industrial sites. This situation led to two environmental
      surveys in these areas, in which the presence of dioxins was studied among other
      parameters. A PCDD/F assessment in soils of the Campo de Gibraltar (Cadiz) was
      carried out from June 2003 to June 2004. A total of 20 samples were collected in
      this study divided in two sampling campaigns. The first 10 samples were taken in
      locations affected by high industrial activity zones as well as in landfills
      (hotspots). The rest of the samples were collected in areas that were not
      expected to be contaminated, such as agricultural zones and forests. I-TEQ values
      of the samples ranged from 0.26 to 15.08 ng/kg dm. In all, 85% of the samples
      were below the limit of 5 ng I-TEQ/kg I-TEQ concentrations of three samples only
      surpassed this limit. These zones corresponded to a landfill, a quarry used for
      dumping chemical product containers and a sample from the sewage system of the
      industrial site. These sites were used neither for agricultural nor for public
      purposes.

PMID- 16564071
TI  - Bioaccumulation and physiological effects of mercury in Sesbania drummondii.
AB  - The accumulation of mercury and its effect on growth, photosynthesis and
      antioxidative responses were studied in Sesbania drummondii seedlings. Mercury
      concentration in shoots as well as in the roots increased with increasing Hg
      concentrations in the growth solution. The accumulation of Hg was more in roots
      than shoots. At 100 mg l-1 Hg concentration, shoots accumulated 998 mg Hg kg -1
      dry weight (dw) while roots accumulated 41,403 mg Hg kg-1 dw. Seedlings growth
      was not significantly affected at lower concentrations of Hg. A concentration of
      100 mg l-1 Hg inhibited growth by 36.8%, with respect to control. Photosynthetic
      activity was assessed by measuring chlorophyll a fluorescence by determination of
      Fv/Fm and Fv/Fo values. Photosynthetic integrity was not affected up to 50 mg l-1
      Hg concentration, however, concentrations higher than 50 mg l-1 affected
      photosynthetic integrity. Sesbania responded to Hg induced oxidative stress by
      modulating non-enzymatic antioxidants [glutathione (GSH) and non-protein thiols
      (NPSH)] and enzymatic antioxidants: superoxide dismutase (SOD), ascorbate
      peroxidase (APX) and glutathione reductase (GR). Glutathione content and GSH/GSSG
      ratio increased up to a concentration of 50 mg l-1 while slight down at 100 mg l
      1 Hg. The content of NPSH significantly increased with increasing Hg
      concentrations in the growth medium. The activities of antioxidative enzymes,
      SOD, APX and GR followed the same trends as antioxidants first increased up to a
      concentration of 50 mg l-1 Hg and then slight decreased. The results of present
      study suggest that Sesbania plants were able to accumulate and tolerate Hg
      induced stress using an effective antioxidative defense mechanisms.

PMID- 16564072
TI  - Effect of sodium selenite supplementation on the levels of prostacyclin I(2) and
      thromboxane A(2) in human.

PMID- 16564073
TI  - The mechanisms and consequences of ultraviolet-induced immunosuppression.
AB  - Exposure to ultraviolet radiation (UVR) can result in immune suppression to
      antigens encountered within a few days of the irradiation. The process leading to
      the down-regulation in immune responses is complex. It is initiated by several
      photoreceptors located in the skin surface, namely DNA, trans-urocanic acid and
      membrane components. The absorption of UVR by these chromophores then leads to
      the release of a wide range of mediators that can affect antigen presenting cells
      locally or systemically. The final steps include the generation of antigen
      specific T cells capable of regulating immunity. The consequences of the UV
      induced changes in the skin immune system for the control of skin cancers,
      infectious diseases including vaccination, and autoimmune diseases are
      considered. Finally, the effects of active vitamin D, synthesised in the
      epidermis following UVR, are discussed in the context of the skin immune
      response.

PMID- 16564074
TI  - The effect of total parenteral nutrition on the survival of terminally ill
      ovarian cancer patients.
AB  - OBJECTIVES: Total parenteral nutrition (TPN) for terminal ovarian cancer patients
      remains controversial. In this study, we compared survival from time of terminal
      intestinal obstruction (TIO) diagnosis in patients who received TPN versus those
      who did not. METHODS: A historical cohort of 55 patients with stage IIIC/IV
      epithelial ovarian cancer hospitalized for TIO between 1994 and 2002 was studied.
      All patients were previously treated with paclitaxel/platinum following
      cytoreductive surgery. Exposure was administration of TPN after TIO. The primary
      outcome was survival from TIO diagnosis to death. Number of chemotherapy cycles
      completed after TIO diagnosis, major complications of TPN, and demographics were
      measured. Survival analysis was performed using Kaplan-Meier methods. RESULTS:
      The median survival from time of TIO diagnosis was 72 days (range 16-485) for
      patients receiving TPN and 41.0 days (range 4-133) for those not receiving TPN (P
      = 0.05), but no difference in survival was observed when adjusting for
      chemotherapy. Overall survival [median 23 (range 6-67) vs. 35 months (range 8
      67), P = 0.03] was shorter for the TPN group. Demographic data were similar in
      both groups. Patients receiving TPN after obstruction were more likely to undergo
      concurrent chemotherapy (64 vs. 26%, P = 0.004). One major TPN-related
      complication was found. CONCLUSIONS: Ovarian cancer patients with TIO receiving
      TPN had a median survival benefit of 4 weeks. This benefit decreased when
      patients were treated with concurrent chemotherapy. Issues of cost, quality of
      life, and human values need to be investigated to assess the full impact of TPN
      in this patient population.

PMID- 16564075
TI  - Vaginal reconstruction following supra-levator total pelvic exenteration.
AB  - BACKGROUND: There are several available techniques for neovaginal reconstruction
      following exenterative gynecologic surgery. However, all methods are associated
      with prolonged operative time and increased morbidity. The Apogee and Perigee
      vaginal vault and prolapse repair systems are innovative and minimally invasive
      procedures that may prove to be effective in controlling the levator defect and
      reconstructing the vagina in patients undergoing supra-levator pelvic
      exenteration. CASE: We present a patient who underwent supra-levator total pelvic
      exenteration for treatment of recurrent squamous cell carcinoma of the cervix.
      Vaginal reconstruction was performed with the Apogee and Perigee systems
      utilizing the porcine mesh (InteXen) from American Medical Systems. The patient
      did well without any postoperative vaginal or small bowel complications.
      CONCLUSION: The Apogee and Perigee systems comprise an innovative technique for
      vaginal vault reconstruction and prolapse repair. These systems may prove useful
      in reconstruction of the pelvis following ultra-radical pelvic procedures for
      recurrent gynecologic malignancies.

PMID- 16564076
TI  - Is intraoperative frozen section analysis of pelvic lymph nodes accurate after
      neoadjuvant chemotherapy in patients with cervical cancer?
AB  - OBJECTIVE: Intraoperative frozen section examination of pelvic lymph nodes is
      frequently used in patients with cervical cancer, some of whom have received
      neoadjuvant chemotherapy (NACT). However, NACT can cause necrosis, fibrosis, or
      keratinization of tumor deposits in extirpated lymph nodes, and it is unclear
      whether intraoperative frozen section analysis of extirpated nodes is accurate
      after NACT. We analyzed the accuracy of frozen section examination of pelvic
      lymph nodes in patients after NACT for cervical cancer. METHODS: We reviewed 134
      patients with invasive cervical cancer who underwent surgery including systematic
      pelvic lymphadenectomy with intraoperative frozen section examination of pelvic
      lymph nodes. Results of frozen section examination were related to definitive
      histology and compared between patient groups of NACT and primary surgery.
      RESULTS: A total of 1670 pelvic lymph nodes were evaluated intraoperatively by
      frozen section examination, and 6689 pelvic lymph nodes were analyzed by final
      histopathology. Overall frozen section analysis had nine false negative results
      among 53 patients with positive lymph nodes (false negative rate, 16.9%). After
      NACT, there were two false negative diagnoses in twelve patients with node
      metastases (false negative rate, 16.7%). No false positive cases were noted. The
      sensitivity and negative predictive value of frozen section examination were 83%
      and 82%, respectively, in patients after NACT, and 83% and 91% at primary
      surgery. CONCLUSION: NACT does not appear to compromise the diagnostic accuracy
      of intraoperative frozen section examination of pelvic lymph nodes in patients
      with cervical cancer.

PMID- 16564077
TI  - Follow-up of ovarian and primary peritoneal carcinoma: the value of physical
      examination in patients with pretreatment elevated CA125 levels.
AB  - OBJECTIVE: To assess the value of routine periodic physical examination in the
      follow-up of ovarian (OvC) and primary peritoneal carcinoma (PPC) patients with
      pretreatment elevated CA125 levels. METHODS: Included were patients who had a
      pretreatment serum CA125 level above normal limits, had completed initial
      treatment, were in complete clinical remission on completion of the initial
      treatment and routinely attended the gynecologic oncology outpatient clinic.
      Recurrence was diagnosed when at least one of the following criteria was
      abnormal: symptoms, physical examination or elevated serum CA125 levels. RESULTS:
      Of 69 patients, a recurrence was diagnosed in 43. Abnormal physical examination
      for diagnosis of recurrence yielded a sensitivity rate of only 34.9%. The
      diagnosis of recurrence was based on an abnormal physical examination alone in 2
      (4.6%) patients. CONCLUSION: In OvC and PPC patients with elevated pretreatment
      CA125 levels, physical examination has a limited impact on the diagnosis of
      recurrence.

PMID- 16564078
TI  - Effect of sex-sorting on the ability of fresh and cryopreserved bull sperm to
      undergo an acrosome reaction.
AB  - Previous studies indicate that sex-sorted sperm exhibit different physiology,
      including fertilizing capacity, from non-sorted sperm. However, differences
      between X- and Y-bearing sperm in their ability to undergo an acrosome reaction
      have never been investigated. This study determined the ability of non-sorted and
      sex-sorted sperm to undergo the acrosome reaction prior to and after
      cryopreservation. Sperm were treated with dilauroylphosphatidylcholine (PC12) to
      induce the acrosome reaction and the percentages of live-acrosome-reacted sperm
      and dead sperm were evaluated. The X- and Y-bearing sperm reacted similarly to
      the PC12 treatment, regardless of whether sperm were assessed prior to or after
      cryopreservation. Fresh control sperm exhibited lower percentages of live sperm
      (60%) than either X- or Y- sorted sperm (69-74%, P<0.05). Percentages of live
      control sperm were also lower after thawing (29-35%) than sex-sorted sperm (55
      58%, P<0.05). Control and sex-sorted fresh sperm responded similarly to PC12
      treatment. However, sex-sorted cryopreserved sperm exhibited higher percentages
      of live-acrosome-reacted sperm (23%) than control sperm (9%, P<0.05) after 40 min
      without PC12 treatment. In addition, cryopreserved control sperm treated with 79
      microM PC12 exhibited higher percentages of live-acrosome-reacted sperm than sex
      sorted sperm. In conclusion, X- and Y-bearing sperm responded similarly to PC12
      treatment. In addition, fresh sexed and non-sorted sperm responded similarly to
      PC12 treatment. However, cryopreserved sex-sorted sperm underwent an acrosome
      reaction more rapidly in the absence of PC12 (over a 40 min period) than the non
      sorted sperm. Therefore, sex-sorting induced changes in sperm membranes that
      accelerated the acrosome reaction process in sperm after cryopreservation.

PMID- 16564079
TI  - Apoptosis in canine corpus luteum during spontaneous and prostaglandin-induced
      luteal regression.
AB  - Spontaneous luteal regression and prostaglandin-induced luteolysis in bitches
      were evaluated by measuring the apoptotic index for DNA fragmentation and the
      relative level of Bax gene expression in ovaries removed from nine untreated
      nonpregnant bitches at selected times during diestrus and in nine pregnant
      bitches after 1 day of administering abortive doses of a PGF-analog gel
      formulation given intravaginally at selected times during gestation. Nonpregnant
      diestrus was divided into three periods (early, mid and late) based on vaginal
      cytology and plasma progesterone concentration. Pregnant bitches were treated
      with a PGF-analog gel at corresponding stages of pregnancy (early, mid and late)
      and evaluated by ultrasound. Another eight pregnant bitches were similarly
      studied and serum progesterone concentrations were determined after 1, 2, 3 or 4
      days of PGF-analog gel. Corpora lutea obtained by ovariohysterectomy were
      analyzed for apoptotic internucleosomal DNA fragmentation relative to that in a
      control cell line (U937), using an apoptotic DNA ladder kit and gel
      electrophoresis and for relative expression of the pro-apoptotic Bax gene by RT
      PCR and electrophoresis. In nonpregnant bitches, the DNA fragmentation apoptotic
      index was greater in late than in early diestrus (P < 0.01). The index after 1
      day of PGF-analog gel was higher in early pregnant bitches than in early diestrus
      bitches (P < 0.05); it was highest in midpregnancy (P < 0.05). The degree of
      apoptosis was related to the number of times PGF-analog gel was administered. Bax
      mRNA was detected in the corpus luteum (CL) and Bax expression increased from
      early to middiestrus in nonpregnant subjects (P < 0.05). Potential elevation in
      Bax due to PGF-analog gel treatment in pregnancy was only significant in relation
      to normal diestrus during early pregnancy (P < 0.01). In conclusion, we inferred
      that the effects of endogenous or exogenous prostaglandin on CL life span in
      bitches involved increases in apoptotic activity and that increased apoptosis was
      implicated in normal luteal regression in nonpregnant bitches.

PMID- 16564080
TI  - Treatment with a subcutaneous GnRH agonist containing controlled release device
      reversibly prevents puberty in bitches.
AB  - In most species, continuous administration of GnRH agonists desensitizes the
      pituitary to GnRH, and blocks ovarian function. The aim of this study was to
      assess the effects of a novel controlled release device containing azagly
      nafarelin (Gonazon) to prevent puberty in young Beagle bitches (mean age: 4.88 +/
      0.32 months). Gonazon containing 18.5 mg azagly-nafarelin (n = 10) or a placebo
      implant (n = 10) was administered subcutaneously. Throughout the 1-year
      treatment, estrus behaviour was monitored weekly. Plasma progesterone
      concentrations, as well as body weight and height, were measured monthly.
      Following implant removal, estrus detection and progesterone measurement were
      continued until occurrence of puberty in all bitches. Control bitches displayed
      puberty (estrus, followed by ovulation) at approximately 11.9 +/- 2.7 (range, 8
      16) months of age. In contrast, none of the Gonazon treated bitches displayed
      puberty during the period when Gonazon was present. Following removal of Gonazon,
      resumption of estrus and ovulation naturally occurred (seven bitches) or was
      induced (three bitches) approximately 8.5 (1.2-14.3) months later. As a
      consequence, age of puberty of the Gonazon treated bitches was 25.5 +/- 5 (18-31)
      months. No clinically detectable side effects were noted in Gonazon treated
      bitches. Height at withers was unaffected by treatment. Changes in body weight
      with time were also unaffected by treatment. Implants were well tolerated and
      generally easy to remove. These data demonstrated that Gonazon safely,
      efficiently and reversibly prevents reproductive function for 1 year in
      prepubertal bitches.

PMID- 16564081
TI  - Fracture resistance of implant-supported screw- versus cement-retained porcelain
      fused to metal single crowns: SEM fractographic analysis.
AB  - OBJECTIVES: The present in vitro study aimed at evaluating the fracture
      resistance of both implant-supported screw- and cement-retained porcelain fused
      to metal (PFM) single crowns. A scanning electron microscope (SEM) evaluation of
      the mode of failure of the specimens was also performed. METHODS: Forty PFM
      premolar-shaped identical single crowns were realized. The restorations were
      divided into two groups: cement-retained (group 1) and screw-retained (group 2)
      prostheses. Compressive loading tests and SEM fractographic analyses were
      performed. The data were statistically analysed by means of the Student's t-test,
      with a confidence interval of 95%. RESULTS: The mean fracture load value was 1657
      (+/-725) N in group 1 and 1281 (+/-747) N in group 2; the statistical analysis
      pointed out no significant differences between the two groups (p=0.115). The mean
      work at maximum load value was 0.775 (+/-0.619) J in group 1 and 0.605 (+/-0.526)
      J in group 2; the statistical analysis pointed out no significant differences
      between the two groups (p=0.355). All the samples were affected by cohesive
      fractures of the porcelain. Screw-retained crowns showed microcracks at the level
      of the occlusal access to the screw and extensive fractures in the whole
      thickness of the ceramics. On the contrary, cement-retained restorations were
      affected by less wide paramarginal fractures of the porcelain. SIGNIFICANCE: A
      stronger implant-prosthetic connection was noticed in cemented restorations group
      than in screw-retained single crowns. Even though negatively influenced by the
      presence of the occlusal access to the screw, the metal-ceramics bond can be
      considered predictable in both the implant-prosthetic connection systems
      analysed.

PMID- 16564082
TI  - Bioactivity and cytocompatibility of zirconia (ZrO(2)) films fabricated by
      cathodic arc deposition.
AB  - Zirconium oxide thin films were fabricated on silicon wafers using a filtered
      cathodic arc system in concert with oxygen plasma. The structure and phase
      composition of the zirconium oxide thin films were characterized by atomic force
      microscopy (AFM), X-ray diffraction (XRD), Rutherford backscattering spectrometry
      (RBS), and transmission electron microscopy (TEM). The bioactivity was assessed
      by investigating the formation of apatite on the film surface after soaking in
      simulated body fluids. Bone marrow mesenchymal stem cells (BMMSC) were used to
      further evaluate the cytocompatibility of the materials. The results indicate
      that the films are composed of stoichiometric ZrO(2) and the composition is quite
      uniform throughout the thickness. Bone-like apatite can be formed on the surface
      of the ZrO(2) thin film in our SBF immersion experiments, suggesting that the
      surface is bioactive. The outermost layer of the ZrO(2) thin film comprises nano
      sized particles that can be identified by AFM images taken on the thin film
      surface and TEM micrographs obtained from the interface between the ZrO(2) thin
      film and apatite layer. The nanostructured surface is believed to be the key
      factor that apatite is induced to precipitate on the surface. Bone marrow
      mesenchymal stem cells are observed to grow and proliferate in good states on the
      film surface. Our results show that ZrO(2) thin films fabricated by cathodic arc
      deposition exhibit favorable bioactivity and cytocompatibility.

PMID- 16564083
TI  - Antibacterial activity of dental composites containing quaternary ammonium
      polyethylenimine nanoparticles against Streptococcus mutans.
AB  - The antibacterial activity of quaternary ammonium polyethylenimine (PEI)
      nanoparticles embedded at 1%w/w with clinically used bonding, flowable and hybrid
      dental composite resins and cured by light polymerization was studied. The
      antibacterial activity was tested with Streptoccocus mutans by: (i) the agar
      diffusion test (ADT); (ii) the direct contact test; (iii) bacterial growth in the
      materials elute; (iv) and scanning electron microscope (SEM). Using the direct
      contact test, antibacterial activity (p<0.001) was found in all three types of
      composite resins incorporated with the synthesized nanoparticles. The effect
      lasted for at least 1 month. SEM demonstrated bacterial debris and no
      streptococcal chains at 24h of bacterial contact. The addition of 1%w/w of
      nanoparticles did not affect the flexural modulus and the flexural strength of
      the dental composite materials. The results indicate that quaternary ammonium PEI
      nanoparticles immobilized in resin-based materials have a strong antibacterial
      activity upon contact without leach-out of the nanoparticles and without
      compromise in mechanical properties.

PMID- 16564084
TI  - Effects of hyaluronan and SPARC on fibroproliferative events assessed in an in
      vitro bladder acellular matrix model.
AB  - Bladder acellular matrix (BAM) is a promising candidate for urinary biomaterials
      development. In the current work we have modified the BAM construct to include
      two biologically active components; hyaluronan (HA) and a peptide (SP4.2) derived
      from secreted protein, acidic, rich in cysteine (SPARC), a matricellular
      glycoprotein. In order to assess the potential of an HA/SP4.2 modified BAM to
      influence cellular functions associated with bladder healing, experiments were
      conducted to evaluate the individual and combined effects of these molecules on
      in vitro fibroproliferative endpoints within a co-culture model. Thiol-modified
      HA (246 kDa, 15 mg/ml)+/-SP4.2 (200 microm) was incorporated and cross-linked
      into BAM disks through disulfide bond formation. The following scaffolds
      compositions were then evaluated in a bladder smooth muscle cell (SMC)-urothelial
      (UEC) cell co-culture model: BAM unmodified; BAM+HA, BAM+SP4.2 (media addition);
      BAM+HA+SP4.2 (media addition); BAM+HA+SP4.2 (matrix incorporated). At 3, 7 and 14
      days post-seeding, SMC-mediated matrix contraction and gelatinolytic activity
      were evaluated. HA-modified BAM exhibited a significantly higher degree of
      contraction and gelatinase activity compared to unmodified BAM. In contrast,
      addition of SP4.2 to BAM produced a negligible effect on contraction, while
      significantly reducing gelatinase activity. Matrices containing both molecules
      displayed significant increases in contraction, while gelatinase activity was
      dependent upon the method of peptide delivery. These results demonstrate that
      both HA and SP4.2 have significant, yet distinct effects on the contractile and
      proteolytic activity of bladder SMCs and suggest that a modified BAM may be
      capable of modulating processes associated with post-surgical graft contracture
      and scar formation.

PMID- 16564085
TI  - The drug encapsulation efficiency, in vitro drug release, cellular uptake and
      cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol
      succinate nanoparticles.
AB  - Paclitaxel is one of the most effective antineoplastic drugs. Its current
      clinical administration is formulated in Cremophor EL, which causes serious side
      effects. Nanoparticle (NP) technology may provide a solution for such poisonous
      adjuvant problems and promote a sustained chemotherapy, in which biodegradable
      polymers play a key role. Our group has successfully synthesized novel
      poly(lactide)-tocopheryl polyethylene glycol succinate (TPGS) (PLA-TPGS)
      copolymers of desired hydrophobic-hydrophilic balance for NP formulation of
      anticancer drugs. The present work is focused on effects of the PLA:TPGS
      composition ratio on drug encapsulation efficiency, in vitro drug release, in
      vitro cellular uptake and viability of the PLA-TPGS NP formulation of paclitaxel.
      The PLA-TPGS copolymers of various PLA:TPGS ratios were synthesized by the ring
      opening polymerization method and characterized by GPC and (1)H NMR for their
      molecular structure. Paclitaxel-loaded PLA-TPGS NPs were prepared by a modified
      solvent extraction/evaporation method and characterized by laser light scattering
      for size and size distribution, scanning electron microscopy for surface
      morphology and zeta potential for surface charge. High performance liquid
      chromatography was used to measure the drug encapsulation efficiency and in vitro
      drug release profile. Cancer cell lines HT-29 and Caco-2 were used to image and
      measure the cellular uptake of fluorescent PLA-TPGS NPs. Cancer cell viability of
      the drug-loaded PLA-TPGS was measured by MTT assay. It was found that the
      PLA:TPGS composition ratio has little effects on the particle size and size
      distribution. However, the PLA-TPGS NPs of 89:11 PLA:TPGS ratio achieved the best
      effects on the drug encapsulation efficiency, the cellular uptake and the cancer
      cell mortality of the drug-loaded PLA-TPGS NPs. This research was also carried
      out in close comparison with the drug-loaded PLGA NPs.

PMID- 16564086
TI  - Bone regeneration on computer-designed nano-fibrous scaffolds.
AB  - The ability to control architectural features in tissue engineering scaffolds is
      critical to the success of neo-tissue regeneration. In this work, reverse solid
      freeform fabrication and thermal phase separation of poly(L-lactic acid) (PLLA)
      solutions were used to create three-dimensional nano-fibrous (NF) scaffolds with
      complex geometries on the macro- and micro-scales. This approach allows for the
      fabrication of NF matrices while having precise control of internal pore size and
      structure, as well as external scaffold shape including architectures generated
      from computed-tomography scans and histological sections. In vitro cell
      cultivation experiments with MC3T3-E1 pre-osteoblasts were performed on NF
      scaffolds and on similarly designed solid-walled (SW) scaffolds that did not have
      nano-fibers. Proliferation studies showed significantly more cells on NF
      scaffolds after 7 d. In differentiation studies, the NF scaffolds displayed more
      uniform matrix and mineral production throughout. Real-time PCR also showed
      significantly higher expression of osteocalcin and bone sialoprotein mRNAs after
      2 and 6 weeks in the NF scaffolds. Expression of type I collagen mRNA was lower
      in NF scaffolds which possibly indicates quicker differentiation on the NF
      substrate. In summary, we controlled the geometry of NF PLLA scaffolds at
      multiple size scales, and the in vitro results showed that these NF scaffolds
      were advantageous to control scaffolds for bone tissue engineering.

PMID- 16564087
TI  - Ectopic bone formation in mice associated with a lactic acid/dioxanone/ethylene
      glycol copolymer-tricalcium phosphate composite with added recombinant human bone
      morphogenetic protein-2.
AB  - A new putty-like material with bone-inducing capacity was made by combining a
      block copolymer of poly d,l-lactic acid with randomly inserted p-dioxanone and
      polyethylene glycol (PLA-DX-PEG) and beta-tricalcium phosphate (beta-TCP) powder
      with added recombinant human bone morphogenetic protein-2 (rhBMP-2). To optimize
      the material's efficacy for bone formation, we formulated the optimal composition
      ratio of the respective constituent that gives the greatest osteoinductive
      efficacy in a mouse model of ectopic bone formation. In this series of studies,
      we investigated the size of ectopic bone mass induced 3 and 6 weeks after
      implantation of the materials composed of 30 mg of PLA-DX-PEG with 2 microg of
      rhBMP-2 and 0, 15, 30, or 60 mg of beta-TCP powder. An additional experiment was
      designed to investigate how content ratios of beta-TCP powder in 30 mg-putty
      implants (0%, 16.7%, 33.3%, 50%, 66.7%, 83.3%, or 100%) for a fixed dose (5
      microg) of the rhBMP-2 altered the size of the induced ossicle. The results from
      the first experiment indicated that the bone yields were linearly dependent on
      the amount of additional beta-TCP powder. In the second experiment, the largest
      ossicles induced by 5 microg of rhBMP-2 were obtained when the polymer/beta-TCP
      ratio was 1/2 in mice. The data provide important insights into the fabrication
      of implants that provide efficacious delivery of rhBMP-2. The new putty-like
      material may be valuable for repairing or regenerating bone in a clinical
      setting.

PMID- 16564088
TI  - Prenatal vitamin C status is associated with placental apoptosis in normal-term
      human pregnancies.
AB  - Pregnancy is associated with increased susceptibility to oxidative stress.
      Deficiencies in antioxidants during pregnancy and placental oxidant-antioxidant
      imbalance may impair the development of the fetoplacental unit or the eventual
      offspring. In order to elucidate the association of prenatal status of vitamin C
      with the oxidative stress and apoptotic activity in normal full-term placentas,
      we evaluated the content of placental lectin-like oxidized low-density
      lipoprotein receptor-1 (LOX-1) and the trophoblast apoptotic index in normal-term
      human pregnancies. Tissue samples of placentas obtained from 80 normal-term
      pregnancies were categorized into 40 cases with a lower level of prenatal vitamin
      C (< 8.997 microg/ml) and 40 cases with a higher level of prenatal vitamin C (>
      or =11.734 microg/ml). We evaluated the placental LOX-1 content and the
      trophoblast apoptotic index with Western blot analysis and immunohistochemistry,
      and then determined their correlation with the prenatal status of vitamin C. We
      confirmed that the trophoblast expression for the endothelial scavenger receptor
      LOX-1 and the apoptotic activity were significantly lower in the group with a
      higher prenatal level of vitamin C, indicating that placental oxidative stress
      and the apoptotic index were associated with the maternal status of vitamin C. We
      therefore postulate that the maternal status of antioxidant vitamins during
      pregnancy can affect fetal development.

PMID- 16564090
TI  - Unusual course of an acute lymphoblastic leukemia case with i(9q) as a sole
      cytogenetic abnormality.
AB  - Chromosomal changes are necessary in determining the classification, prognosis
      and using the appropriate therapeutic regimen in acute leukemia. Isochromosomes
      are uncommon chromosome aberations in childhood acute lymphoblastic leukemia
      (ALL) and the effect of i(9q) is not well established. We present an 8-year-old
      male case of pre-B ALL who has an unusual course at diagnosis. He was
      hospitalized three times in three different hospitals and blastic cells
      disappeared after the first hospitalization following blood transfusion without
      chemotherapy. In the following two hospitalizations no blastic cell was observed
      and transfused with a pack of erythrocyte suspension each time. In the fourth
      hospitalization, bone marrow aspiration revealed L1 type of lymphoid blast cell
      infiltration. The remission was achieved on the 15th day of the induction therapy
      and he has been in remission for the last 6 months. This unusual presentation and
      early remission achieved by induction therapy in this patient may support the
      literature that isochromosome 9q has a favourable outcome in childhood ALL.

PMID- 16564089
TI  - Diverse calcium channel types are present in the human placental
      syncytiotrophoblast basal membrane.
AB  - The functional expression of calcium channels has been scarcely studied in human
      placental syncytiotrophoblast. We have presently sought to characterize Ca(2+)
      currents of the healthy syncytiotrophoblast basal membrane using purified basal
      membranes reconstituted in giant liposomes subjected to patch-clamp recordings.
      We detected presence of channels with high permeability to Ca(2+) (relative
      PCa/PK up to 99.5) using K(+) solutions in symmetric conditions. Recordings
      performed in Ba(2+) gradients showed Ba(2+)-conducting channels in 100% of
      experiments. Ba(2+) total patch currents were consistently blocked by addition of
      NiCl(2), Nifedipine (L-type voltage-gated calcium channel blocker) or Ruthenium
      Red (TRPV5-TRPV6 channel blocker); Nifedipine and Ruthenium Red exerted a
      synergic blocking effect on Ba(2+) total patch currents. Immunohistochemistry of
      placental villi sections evidenced presence of alpha(1) subunit of voltage-gated
      calcium channels and TRPV5-TRPV6 channels in basal and apical syncytiotrophoblast
      plasma membranes; these three calcium channels were also detected in purified
      basal and apical fractions using Western blot. These results show the presence of
      three types of calcium channels in the syncytiotrophoblast basal membrane by both
      functional and molecular means. These basal membrane calcium channels would not
      be directly involved in mother-to-fetus Ca(2+) transport, but could participate
      in other relevant trophoblast processes, such as exocytosis and Ca(2+) transport
      regulation.

PMID- 16564091
TI  - High-valent transition metal corrolazines.
AB  - High-valent metalloporphyrin intermediates have been implicated as key players in
      numerous mechanistic proposals for both biological (e.g., heme protein) and
      synthetic porphyrin mediated transformations. However, the direct observation of
      these species is quite challenging because of the inherently short lifetimes of
      many of these metalloporphyrin intermediates. This review focuses on our own
      efforts to synthesize and study a new class of porphyrinoid compounds called
      corrolazines, which are designed to stabilize high-valent species for direct
      analysis. These compounds are related to corroles, which also exhibit the unusual
      ability to stabilize high oxidation states, and the reactivity and physical
      properties of relevant corrole and porphyrin analogs are compared with the
      appropriate corrolazines. The chemistry of Cu, Co, V, and Mn are highlighted,
      with a particular emphasis on the reactivity of high-valent manganese-oxo
      complexes.

PMID- 16564092
TI  - Vertebral osteomyelitis: long-term disability assessment and prognostic factors.
AB  - In the present study, we quantified the long-term sequelae of a series of
      patients diagnosed with vertebral osteomyelitis during the period 1990-2002 in
      Albacete (Spain), using two validated questionnaires of spinal dysfunction and
      also one pain and one global health assessment. It was possible to interview 69
      (78%) patients diagnosed with vertebral osteomyelitis, and an additional 90
      "normal" people were recruited as controls to establish normal values. We also
      carried out a multivariate analysis to identify independent risk factors. We
      found only a 33% rate of spinal disability, only 3% severe, assessed by the
      Oswestry and HAQ for ankylosing spondylitis questionnaires, a median of 5.4 years
      after treatment. Pain and global health assessment did not correlate with spinal
      function questionnaires. Independent predictors of long-term disability were the
      followings: neurological impairment at the time of diagnosis (RR=7.1, 95% CI 1.3
      10.2), time to diagnosis > or = 8 weeks (RR=4.4, 95% CI 1.5-7.9) and debilitating
      disease (RR=3.9, 95% CI 1.2-7.5). Standardized spinal function questionnaires are
      useful measures to assess long-term outcome of vertebral osteomyelitis that
      facilitates comparison between case series and identification of risk factors.

PMID- 16564093
TI  - Fatty acid elongases in mammals: their regulation and roles in metabolism.
AB  - A significant amount of the fatty acids synthesized by the cytosolic enzyme
      complex fatty acid synthase (FAS) or taken up by the diet are further elongated
      into very long chain fatty acids (VLCFA) in a four-step reaction cycle by
      membrane-bound enzymes predominantly located in the endoplasmic reticulum.
      Members of the Elovl (elongation-of-very-long-chain-fatty acids) gene family
      encode for enzymes (elongases), which are believed to perform the first,
      regulatory, step (condensation) in the elongation cycle in mammals. The family of
      enzymes consists of at least six members in mouse and human, believed to carry
      out substrate-specific elongation with fatty acids of different lengths and
      degrees of unsaturation. The ability to synthesize VLCFA is a ubiquitous system
      found in different organs and cell types. However, VLCFAs seldom occur
      unesterified. Instead, they are joined either by an ester or amide linkage to a
      broad variety of different lipid species. VLCFA are most commonly found as
      building blocks in sphingolipids, although they are also important constituents
      of glycerophospholipids, triacylglycerols, sterol- and wax-esters. To generalize,
      the fatty acid elongases can be divided into two major groups: (a) enzymes which
      are suggested to be involved in the elongation of saturated and monounsaturated
      VLCFA (ELOVL1, 3 and 6) and (b) enzymes which are elongases of polyunsaturated
      fatty acids (PUFA) (ELOVL2, 4 and 5). All the elongases exhibit specific spatial
      and temporal expression. In this review, we will present and discuss the
      regulation of the mammalian fatty acid elongases and their potential role in
      lipid metabolism. We will consider both the biochemical functions of the
      proteins, as well as their role in a more physiological context.

PMID- 16564094
TI  - Reversible vagal blockade in conscious rats using a targeted delivery device.
AB  - Reversible methods of nerve blockade greatly aid neurophysiological and
      behavioral studies. We have developed an implantable device for the local
      delivery of anesthetics to the area surrounding the vagal nerve in rats. The
      device consists of a thick silicone tube for insulating the nerves from the
      surrounding tissue, and a thin silicone tube for the infusion of anesthetics into
      the insulating tube. The in vivo performance of the device was tested
      electrophysiologically, and cardiovascular responses to vagal stimulation were
      measured in conscious animals. Nerve conductivity was completely blocked by
      injection of a small amount (<20 microl) of 1% lidocaine, with conductivity
      subsequently recovering gradually after 10-40 min. Electrical stimulation of the
      right vagus nerve in conscious rats increased arterial pressure while decreasing
      heart rate. The local blockade of afferent fibers abolished the arterial pressure
      response but preserved the bradycardic response to vagal nerve stimulation. The
      targeted delivery device was useful for reversible vagal blockade in conscious
      rats.

PMID- 16564095
TI  - Reply to "The role of soluble interleukin-6 receptor in inflammatory diseases"
      [Immunol Lett 2005;98(1):171].
AB  - We agree with the comments of Mr. Maggio and colleagues. The exact role of serum
      IL-6R and the relation between this and the IL-6/sIL-6R complex in inflammatory
      disorders has not been completely clarified. We suggest a discrepancy between sIL
      6R concentrations and measurable IL-6/sIL-6R complex, not excluding the positive
      contribution of sIL-6R as a marker of neuro-immunoregulatory and inflammatory
      status in the central nervous system.

PMID- 16564096
TI  - Selective role of PKCbeta enzymatic function in regulating cell survival mediated
      by B cell antigen receptor cross-linking.
AB  - Cross-linking of the B cell antigen receptor (BCR) results in the activation of
      several protein tyrosine kinases leading to phospholipase C-gamma2-dependent
      phospholipid hydrolysis and Ca2+ mobilization, followed by activation of the
      protein kinase C (PKC) family members. Sustained Ca2+ release in B lymphocytes is
      dependent on the membrane localization and activation of the protein tyrosine
      kinase BTK. Ca2+ release is a tightly regulated process involving BTK membrane
      localization through its phosphorylation by PKCbeta. A selective role of PKCbeta
      in B cell signaling was first revealed by the characterization of PKCbeta
      knockout mice, which displayed decreased B cell proliferation in response to
      various mitogenic stimuli. However, it is not clear whether the B cell defects
      displayed by the PKCbeta knockout mice are due a B cell developmental defect or
      the scaffolding function of PKCbeta, resulting in a defect in the recruitment or
      formation of signal transducing complex molecules. Thus, in this report we
      investigated the effects of pharmacologic inhibition of the catalytic function of
      PKCbeta on B cell survival and growth. Treatment of Daudi B lymphoma cell line
      with a selective PKCbeta inhibitor, LY333531, inhibited anti-IgM-induced
      phosphorylation of BTK on Ser180 in a concentration-dependent manner, which was
      concomitant with an increase in BTK activation, and Ca2+ mobilization. In primary
      splenic B cells, LY333531 inhibited BCR-induced B cell proliferation, but did not
      affect basal or LPS-induced proliferation. Finally, LY333531 treatment resulted
      in the induction of apoptosis of anti-IgM-activated B cells, which corroborated
      with their inability to up-regulate pro-survival factors, Bcl-X(L) and Bcl-2.
      These results support the important and selective role of the PKCbeta enzymatic
      function in controlling Ca2+ release during BCR signaling leading to B lymphocyte
      survival and growth.

PMID- 16564097
TI  - Treatment strategy for iatrogenic nasal vestibular stenosis in young children.
AB  - Iatrogenic nasal vestibular stenosis is an uncommon complication of supportive
      care in neonates. There is minimal literature describing this entity; previous
      treatment strategies focus on correction with local flaps or skin grafts. We
      describe symptomatic iatrogenic vestibular stenosis treated successfully with
      endoscopic lysis of synechiae and nasal stenting. Three children with nasal
      stenosis were identified from 2003 to 2004 at a large academic tertiary care
      medical center. All patients were born premature (25-34 weeks). Two developed
      vestibular stenosis after extended use of nasal CPAP; one developed unilateral
      nasal stenosis 4 years after use of a nasal feeding tube. Age at time of surgical
      repair was from 4 months to 5 years. Two patients (4 and 5 months) presented with
      nasal airway obstruction, and difficulty breathing during feeding. One patient (5
      years) presented with right-sided nasal obstruction and nasal whistling.
      Endoscopic lysis of nasal synechiae and release of vestibular scarring was
      performed in all three cases without complication. Nasal stenting with a modified
      endotracheal tube was used for 4-6 weeks. Topical Mitomycin C was utilized in two
      patients. All patients had complete resolution of airway symptoms after stent
      removal and all three remain asymptomatic 1 year after repair with no recurrence
      of vestibular stenosis. Nasal vestibular stenosis is a rare complication
      following supportive care in premature infants, causing airway and feeding
      difficulties in the obligate nasal breather. This can be successfully corrected
      with endoscopic repair, nasal stenting and application of Mitomycin C.

PMID- 16564098
TI  - Human papillomavirus genotyping using a modified linear array detection protocol.
AB  - A standardized PCR-based linear array genotyping assay has been developed (Roche
      Molecular Systems) allowing the concurrent typing of 37 human papillomavirus
      (HPV) types. A component of this assay, the PCR amplicon detection protocol,
      requires the use of a shaking water-bath incubator for amplicon/probe
      hybridization and subsequent stringent washing, which many laboratories may find
      cumbersome or simply not possess. In this study, the utility of a dry-air
      incubator in substitution of the recommended shaking water-bath for use in this
      assay was confirmed. DNA was extracted by AmpliLute method from 150 PreservCyt
      specimens collected from patients undergoing ablation treatment for
      histologically confirmed cervical abnormality. The DNA was amplified by PCR and
      amplicons detected by both standard and modified protocols, varying only by the
      method of incubation for DNA hybridization and stringent washing. Identical HPV
      type profiles were generated in 149/150 (99.3%) of the specimens tested by both
      protocols, representing a near perfect level of concordance (kappa = 0.98). It
      was proposed that this modification would markedly simplify the detection
      process, reduce setup time and eliminate the potential for water spillover,
      thereby allowing more laboratories to adopt this method subsequent to in-house
      validation.

PMID- 16564099
TI  - Synthesis and the biological evaluation of 2-benzenesulfonylalkyl-5-substituted
      sulfanyl-[1,3,4]-oxadiazoles as potential anti-hepatitis B virus agents.
AB  - Current treatments for chronic hepatitis B virus (HBV) infection include the use
      of interferon-alpha and of nucleoside analogs lamivudine, adefovir and entecavir.
      However, the use of interferon-alpha has many side effects while that of
      nucleosidic inhibitors can lead to the emergence of resistant viruses. Hence, new
      drugs for the treatment of HBV infection are still highly desired. Oxadiazoles
      have been observed to exhibit antiviral activities against RNA viruses. In this
      study, a facile synthesis of 2-benzenesulfonylalkyl-5-substituted-sulfanyl
      [1,3,4]-oxadiazoles is reported. The compounds were then evaluated for their anti
      HBV activity. 1-[2-[5-(1-Benzenesulfonyl-propyl)-[1,3,4]oxadiazol-2-yl-sulfanyl]
      ethyl]-4-(2-methoxy-phenyl)-piperazine (1i) was able to inhibit the expression of
      the viral antigens, HBsAg and HBeAg in a concentration-dependent manner with no
      cytotoxic effects and without any effects on the expression of viral transcripts.
      Concentration- and time-dependent reductions in virion production were also
      observed. The inhibition of virion production was comparable to that of
      lamivudine and EC(50) values of 1.63 and 2.96 microM were obtained for compound
      1i and lamivudine, respectively. Thus, in addition to the antiviral effects on
      RNA viruses, oxadiazoles also have anti-HBV activities.

PMID- 16564100
TI  - Tryptase activates PKB in inflammatory reaction in ECV304 cells.
AB  - Tryptase is involved in proteinase-activated receptor-2 (PAR-2) mediated up
      regulation of IL-8 expression. The present report showed the effects of tryptase
      on gene expression and activation, including up-regulation IL-8 expression. The
      expression of mRNA for NF-kappaB first increased at 1 h after tryptase-treatment
      (1 ng/ml) and reached the plateau after 4 h. The NF-kappaB mRNA increased by 3
      fold (n = 3, P < 0.05), AP-1 by 2-fold (n = 3, P < 0.05), and PKB by 10-fold (n =
      3, P < 0.05). However, tryptase-treatment did not affect the expression of JNK
      and p38 MAPK when compared with control cells at mRNA level. Furthermore, in
      addition to increasing phosphorylation of p38 MAPK, tryptase-treatment also
      increased phosphorylation of PKB by 2-fold at 15 min following the treatment. The
      up-regulation and phosphorylation of PKB by tryptase could be abolished by either
      phosphoinositol-3-kinase (PI3K) inhibitor (LY294002) at 10 microM or antisense
      PKB cDNA transfection. The up-regulation of NF-kappaB expression could be
      inhibited by LY294002 and antisense PKB cDNA. These results indicate that
      tryptase can activate PI3K-PKB pathway and enhance IL-8 expression.

PMID- 16564101
TI  - Decision analysis model for paratuberculosis control in commercial dairy herds.
AB  - A previous economic test-and-cull decision analysis model has been strengthened
      and updated with current epidemiologic information. Created using Excel and
      PrecisionTree software, the model incorporates costs and benefits of herd
      management changes, diagnostic testing, and different management actions based on
      test results to control paratuberculosis in commercial dairy herds. This novel
      "JD-Tree" model includes a herd management decision node (four options), a
      test/no test decision node (two options), a diagnostic test choice decision node
      (five options), test result chance nodes (four levels of possible results), and
      test action decision nodes (three options; cull, manage, no action). The model
      culminates in a chance node for true infection status. Outcomes are measured as a
      net cost-benefit value to the producer. The model demonstrates that improving
      herd management practices to control infection spread (hygiene) is often more
      cost-effective than testing; not all herds should test as part of a
      paratuberculosis control program. For many herds, low-cost tests are more useful
      than more sensitive, higher cost tests. The model also indicates that test
      positive cows in early stages of infection may be retained in the herd to
      generate farm income, provided they are managed properly to limit infection
      transmission. JD-Tree is a useful instructional tool, helping veterinarians
      understand the complex interactions affecting the economics of paratuberculosis
      control and to define the accuracy and cost specifications of better diagnostic
      tests.

PMID- 16564102
TI  - Performance assessment in the context of multiple objectives: a multivariate
      multilevel analysis.
AB  - The pursuit of multiple objectives by public sector organisations makes it
      difficult to assess and compare their performance. Considering objectives in
      isolation ignores the possibility of correlations between objectives, and a
      single index of performance requires subjective judgements to be made about the
      relative value of each objective. An alternative approach is to estimate a
      multivariate system of equations in which objectives are analysed individually
      but correlations across objectives are considered explicitly. We analyse the
      performance of English health authorities against 13 objectives using
      hierarchical data for electoral wards that are nested within health authorities.
      We find evidence of correlation across objectives, suggesting that some are
      complementary and others subject to trade-off. The estimates generated when
      assessing performance with multivariate multilevel models as compared to ordinary
      least squares or multilevel models differ, with the magnitudes varying by
      objective and health authority.

PMID- 16564103
TI  - Cellular death of two non-Saccharomyces wine-related yeasts during mixed
      fermentations with Saccharomyces cerevisiae.
AB  - The early death of two non-Saccharomyces wine strains (H. guilliermondii and H.
      uvarum) during mixed fermentations with S. cerevisiae was studied under
      enological growth conditions. Several microvinifications were performed in
      synthetic grape juice, either with single non-Saccharomyces or with mixed S.
      cerevisiae/non-Saccharomyces inocula. In all mixed cultures, non-Saccharomyces
      yeasts grew together with S. cerevisiae during the first 1-3 days (depending on
      the initial inoculum concentration) and then, suddenly, non-Saccharomyces cells
      began to die off, regardless of the ethanol concentrations present. Conversely,
      in both non-Saccharomyces single cultures the number of viable cells remained
      high (ranging 10(7)-10(8) CFU ml(-1)) even when cultures reached significant
      ethanol concentrations (up to 60-70 g l(-1)). Thus, at least for these yeast
      strains, it seems that ethanol is not the main death-inducing factor.
      Furthermore, mixed cultures performed with different S. cerevisiae/ H.
      guilliermondii inoculum ratios (3:1; 1:2; 1:10; 1:100) revealed that H.
      guilliermondii death increases for higher inoculum ratios. In order to
      investigate if the nature of the yeast-yeast interaction was related or not with
      a cell-cell contact-mediated mechanism, cell-free supernatants obtained from 3
      and 6 day-old mixed cultures were inoculated with H. guilliermondii pure
      cultures. Under these conditions, cells still died and much higher death rates
      were found for the 6 days than for the 3 day-old supernatants. This strongly
      indicates that one or more toxic compounds produced by S. cerevisiae triggers the
      early death of the H. guilliermondii cells in mixed cultures with S. cerevisiae.
      Finally, although it has not been yet possible to identify the nature of the
      toxic compounds involved in this phenomenon we must emphasise that the S.
      cerevisiae strain used in the present work is killer sensitive with respect to
      the classical killer toxins, K1, K2 and K28, whereas the H. guilliermondii and H.
      uvarum strains are killer neutral.

PMID- 16564104
TI  - [Spinal manipulations in sciatica].
AB  - Spinal manipulations have been shown to be efficient for common low back pain;
      they remain an option in the treatment of symptomatic lumbar disk herniation.
      From data in the literature, the author discusses the interest of spinal
      manipulations with a "thrust" at the level of disk herniation and concludes that
      this therapy, performed by an experienced physician and under conditions of
      strict application, could be an option in the treatment of subacute and chronique
      disc herniation.

PMID- 16564105
TI  - PROPAT: a study to improve the quality and reduce the cost of diabetes care.
AB  - OBJECTIVE: In PROPAT we implemented an integrated approach to diabetes care
      designed to improve the quality and reduce the cost of care. STUDY DESIGN AND
      METHODS: PROPAT was a case-control study matching patients by age and gender
      (diabetes:control ratio 1:2) within IOMA, a public employment-based health
      maintenance organization (HMO) of the Province of Buenos Aires, Argentina. Costs
      were evaluated using prevalence data from an HMO perspective. We currently report
      clinical and biochemical data and costs from the first 297 patients enrolled who
      completed 1 year in PROPAT, and compare them with those derived from control
      patients. RESULTS: All recommended practices recorded as care provided at
      baseline increased significantly 1 year after implementing PROPAT, with a
      parallel significant improvement in several clinical and biochemical parameters,
      and markedly lower total annual per capita costs. CONCLUSIONS: These results
      demonstrate that the implementation of a comprehensive diabetes care program can
      simultaneously improve quality while reducing costs.

PMID- 16564106
TI  - Let's assume that hepatitis C reduces the cardiovascular risk in dialysis
      patients: are there practical implications?

PMID- 16564107
TI  - Aspartyl-(asparaginyl)-beta-hydroxylase regulates hepatocellular carcinoma
      invasiveness.
AB  - BACKGROUND/AIMS: We measured aspartyl (asparaginyl)-beta-hydroxylase (AAH) gene
      expression in human hepatocelluar carcinoma and surrounding uninvolved liver at
      both the mRNA and protein level and examined the regulation and function of this
      enzyme. METHODS: Since growth of HCC is mediated by signaling through the insulin
      receptor substrate, type 1 (IRS-1), we examined-if AAH is a downstream gene
      regulated by insulin and IGF-1 in HCC cells. In addition, IRS-1 regulation of AAH
      was examined in a transgenic (Tg) mouse model in which the human (h) IRS-1 gene
      was over-expressed in the liver, and an in vitro model in which a C-terminus
      truncated dominant-negative hIRS-1 cDNA (hIRS-DeltaC) was over-expressed in FOCUS
      HCC cells. The direct effects of AAH on motility and invasiveness were examined
      in AAH-transfected HepG2 cells. RESULTS: Insulin and IGF-1 stimulation increased
      AAH mRNA and protein expression and motility in FOCUS and Hep-G2 cells. These
      effects were mediated by signaling through the Erk MAPK and PI3 kinase-Akt
      pathways. Over-expression of hIRS-1 resulted in high levels of AAH in Tg mouse
      livers, while over-expression of hIRS-DeltaC reduced AAH expression, motility,
      and invasiveness in FOCUS cells. Finally, over-expression of AAH significantly
      increased motility and invasiveness in HepG2 cells, whereas siRNA inhibition of
      AAH expression significantly reduced directional motility in FOCUS cells.
      CONCLUSIONS: The results suggest that enhanced AAH gene activity is a common
      feature of human HCC and growth factor signaling through IRS-1 regulates AAH
      expression and increases motility and invasion of HCC cells. Therefore, AAH may
      represent an important target for regulating tumor growth in vivo.

PMID- 16564108
TI  - Long term care financing in four OECD countries: fiscal burden and distributive
      effects.
AB  - This paper compares long term care (LTC) systems in four OECD countries (UK,
      Japan, Sweden and Germany). In the UK, provision is means tested, so that out of
      pocket payments depend on levels of income, savings and assets. In Sweden, where
      the system is wholly tax-financed, provision is essentially free at the point of
      use. In Germany and Japan, provision is financed from recently introduced
      compulsory insurance schemes, although the details of how each scheme operates
      and the distributive consequences differ somewhat. The paper analyses the effects
      of importing the other three countries' systems for financing LTC into the UK,
      focussing on both the distributive consequences and the tax burden. It finds that
      the German system would not be an improvement on the current UK system, because
      it uses a regressive method of financing. Therefore, the discussion of possible
      alternatives to the present UK system could be restricted to a general tax-based
      system as used in Sweden or the compulsory insurance system as used in Japan. The
      results suggest that all three systems would imply increased taxes in the UK.

PMID- 16564109
TI  - Novel tools to unravel molecular mechanisms in cilia-related disorders.
AB  - Cilia are hair-like organelles extending from the cell surface that execute
      motile (e.g. respiratory cilia) and/or sensory functions (e.g. renal monocilia).
      The basic ultrastructure of cilia and flagella has been well established by
      electron microscopy. Several recent reports have now provided intriguing new
      insights into the complex molecular composition of cilia and flagella. These data
      from genome, proteome and transcriptome analyses will facilitate the systematic
      discovery and understanding of genes responsible for human cilia-related
      diseases, such as primary ciliary dyskinesia, polycystic kidney disease and male
      sterility.

PMID- 16564110
TI  - Pharmacogenetic studies of epilepsy drugs: are we there yet?
AB  - One of the mantras of scientists working in the field of pharmacogenetics is 'the
      right dose for the right patient'. A recent article has gone someway towards
      demonstrating that this goal can be achieved using genetic approaches. It is one
      of the first reports to show that a specific polymorphism can predict the maximum
      tolerated dose of two anti-epileptic drugs. However, further studies are
      necessary to validate these observations.

PMID- 16564111
TI  - Needle-free vaccine delivery.
AB  - The search for methods of vaccine delivery not requiring a needle and syringe has
      been accelerated by recent concerns regarding pandemic disease, bioterrorism, and
      disease eradication campaigns. Needle-free vaccine delivery could aid in these
      mass vaccinations by increasing ease and speed of delivery, and by offering
      improved safety and compliance, decreasing costs, and reducing pain associated
      with vaccinations. In this article, we summarize the rationale for delivery of
      needle-free vaccines and discuss several methods currently in use and under
      development, focusing on needle-free injection devices, transcutaneous
      immunization, and mucosal immunization. Jet injectors are needle-free devices
      that deliver liquid vaccine through a nozzle orifice and penetrate the skin with
      a high-speed narrow stream. They generate improved or equivalent immune responses
      compared with needle and syringe. Powder injection, a form of jet injection using
      vaccines in powder form, may obviate the need for the "cold chain."
      Transcutaneous immunization involves applying vaccine antigen and adjuvant to the
      skin, using a patch or "microneedles," and can induce both systemic and mucosal
      immunity. Mucosal immunization has thus far been focused on oral, nasal, and
      aerosol vaccines. Promising newer technologies in oral vaccination include using
      attenuated bacteria as vectors and transgenic plant "edible" vaccines. Improved
      knowledge regarding the immune system and its responses to vaccination continues
      to inform vaccine technologies for needle-free vaccine delivery.

PMID- 16564112
TI  - Third-line chemotherapy for small cell lung cancer.
AB  - Efficacy of third-line chemotherapy treatment for small cell lung cancer (SCLC)
      is unknown. We present our experience with third-line chemotherapy for recurrent
      SCLC. Between January 1996 and July 2004 all consecutive patients treated for
      SCLC were retrospectively studied. We recorded patient characteristics, treatment
      details for each subsequent regimen, response to chemotherapy and survival. From
      191 patients treated with chemotherapy 35 patients (18%) received third-line
      chemotherapy. At the start of third-line therapy, median age was 58 years (range
      36-77), male/female 54%/46%, and ECOG performance score was 0/1/2/3 in
      15%/64%/12%/9% of patients. Median time from diagnosis till start of third-line
      treatment was 15 months (range 5-34). Tumor response to first-line, second-line,
      and third-line therapy was 91%, 51%, and 26%, respectively. Median survival time
      estimated from the start of third-line treatment was 5 months (range 1-15). No
      toxic deaths were observed. Comparison of characteristics of patients who were
      treated with third-line chemotherapy with patients treated with maximally two
      lines of chemotherapy revealed that those who received third-line therapy were
      younger (p<0.001), had a better performance score (p<0.001), and had a better
      response to first-line treatment (p=0.004). In conclusion, third-line
      chemotherapy is still active in one in four SCLC patients.

PMID- 16564113
TI  - Endomorphin1 and endomorphin2, endogenous potent inhibitors of electrical field
      stimulation (EFS)-induced cholinergic contractions of rat isolated bronchus.
AB  - In the present study, we determined whether endomorphin1 (EM1) and endomorphin2
      (EM2), selective endogenous mu-opioid receptor (MOR) agonists, inhibited the
      response to EFS in rat isolated bronchus in a concentration- and frequency
      dependent manner. EM1 (1 microM) produced significant inhibition at relatively
      low frequencies (< 5 Hz) (74.02 +/- 5.53%, 56.16 +/- 10.24% and 37.64 +/- 5.92%
      inhibition at 1, 2 and 4 Hz, respectively, p < 0.05 versus control), but no
      significant inhibition at 8, 16, 32 and 64 Hz (17.15 +/- 9.4%, 14.51 +/- 4.23%,
      9.11 +/- 2.38% and 5.93 +/- 3.5%, respectively, p > 0.05 versus control). Similar
      modulations were observed in response to EM2 (1 microM). It is therefore
      considered that the inhibition effects of EM1 and EM2 may take place at
      frequencies under physiological conditions. Furthermore, EM1 and EM2 (0.01-10
      microM) induced inhibition of cholinergic constriction in a dose-dependent manner
      at 1, 2 and 4 Hz. The inhibitory effect on EFS was blocked by the opioid receptor
      antagonist naloxone (10 microM), indicating that opioid receptors were involved.
      Neither EM1 nor EM2 (1 microM) had an effect on the contractile response to
      exogenous acetylcholine, indicating a prejunctional effect. All the results
      indicate that EM1 and EM2 are potent inhibitors of EFS-induced cholinergic
      bronchoconstriction. These also imply that EM1 and EM2 may modulate cholinergic
      bronchoconstriction under physiological conditions and that these tetrapeptides
      could have therapeutic potential in the treatment of airway diseases.

PMID- 16564114
TI  - Signaling involved in pituitary adenylate cyclase-activating polypeptide
      stimulated ADNP expression.
AB  - Activity-dependent neurotrophic protein (ADNP) was discovered as a novel response
      gene for VIP and has neuroprotective potential. When the VIP paralog, PACAP38 was
      added to mouse neuron-glia co-cultures, it induced ADNP mRNA expression in a
      bimodal fashion at subpico- and nanomolar concentrations with greater response at
      subpicomolar level. The response was attenuated by a PAC1-R antagonist at both
      concentrations and by a VPAC1-R antagonist at nanomolar concentration only. An
      IP3/PLC inhibitor attenuated the response at both concentrations of PACAP38, but
      a MAPK inhibitor had no effect. A PKA inhibitor suppressed the response at
      nanomolar concentration only. These findings suggest that ADNP expression is
      mediated through multiple receptors and signaling pathways that are regulated by
      different concentrations of PACAP.

PMID- 16564115
TI  - The epidemiology of varicella and herpes zoster in The Netherlands: implications
      for varicella zoster virus vaccination.
AB  - We studied the epidemiology of varicella (chickenpox) and herpes zoster
      (shingles) in The Netherlands to assess the desirability to implement routine
      varicella zoster virus vaccination in The Netherlands. Data on seroprevalence of
      varicella zoster virus in the general population (1995-1996), consultations of
      general practitioners for varicella (2000-2002) and herpes zoster (1998-2001) and
      hospital admissions due to varicella (1994-2001) and herpes zoster (1994-2001) in
      The Netherlands were analysed. The seropositivity increased sharply with age from
      18.4% for both 0- and 1-year-olds, to 48.9%, 59.0%, 75.7% and 93.0% for 2-, 3-, 4
      and 5-year-olds, respectively, and varied between 97.5% and 100% for older age
      groups. The average annual incidence of GP-consultations amounted to 253.5 and
      325.0 per 100,000 for varicella and herpes zoster, respectively. The incidence of
      hospital admission due to varicella and herpes zoster was 1.3 (2.3 including side
      diagnosis) and 2.7 (5.8) per 100,000, respectively. Whilst for varicella, the
      incidence of GP-consultations and hospital admissions were highest in childhood,
      for herpes zoster, these were highest in elderly. Insight into epidemiology of
      varicella zoster is needed for the assessment of the desirability of introduction
      of routine varicella zoster vaccination.

PMID- 16564116
TI  - The MMR vaccination and autism controversy in United Kingdom 1998-2005:
      inevitable community outrage or a failure of risk communication?
AB  - BACKGROUND: The report of an hypothesised link between measles-mumps-rubella
      (MMR) vaccination and autism in 1998 became a major public health issue in the
      United Kingdom (UK), leaving most experts surprised by the overwhelming influence
      it had on public opinion about MMR vaccination. Coverage rates fell dramatically,
      and did not start to recover until 2004. Could this public reaction have been
      predicted? METHODS: We used Sandman's model of components predicting community
      outrage to assess the MMR controversy. RESULTS: The controversy fulfilled all of
      Sandman's 12 primary components and six of the eight additional components.
      CONCLUSIONS: The Sandman model provided a useful framework to analyse this
      controversy and explained a significant portion of the community reaction and
      subsequent fall in vaccination coverage rates.

PMID- 16564117
TI  - Vertical migration of 134Cs bearing soil particles in arid soils: implications
      for plutonium redistribution.
AB  - Vertical migration of plutonium in soils at the Waste Isolation Pilot Plant
      (WIPP) and the Rocky Flats Environmental Technology Site (RFETS) was evaluated
      based on observed 134Cs migration in soil column experiments. After applying
      134Cs-labeled soil particles to the surfaces of large, undisturbed soil cores
      collected from each site, resulting soil columns were subjected to experimental
      cycles of irrigation plus drying (treatment columns) or to cycles of irrigation
      only (control columns). Mean losses of 134Cs inventory from soil surfaces were
      3.1 +/- 0.6% cycle(-1) and 0.7 +/- 0.6% cycle(-1) respectively for RFETS
      treatment and control columns. WIPP columns had mean respective losses of 1.3 +/-
      1.2% cycle(-1) and 0.5 +/- 0.2% cycle(-1). Bulk transport of labeled soil
      particles through soil cracks was an important process in RFETS soils, accounting
      for 64-86% of total 134Cs migration. Colloidal transport processes governed
      migration in WIPP soils.

PMID- 16564118
TI  - Further validation of the HPCD-technique for the evaluation of PAH microbial
      availability in soil.
AB  - There is currently considerable scientific interest in finding a chemical
      technique capable of predicting bioavailability; non-exhaustive extraction
      techniques (NEETs) offer such potential. Hydroxypropyl-beta-cyclodextrin (HPCD),
      a NEET, is further validated through the investigation of concentration ranges,
      differing soil types, and the presence of co-contaminants. This is the first
      study to demonstrate the utility of the HPCD-extraction technique to predict the
      microbial availability to phenanthrene across a wide concentration range and
      independent of soil-contaminant contact time (123 d). The efficacy of the HPCD
      extraction technique for the estimation of PAH microbial availability in soil is
      demonstrated in the presence of co-contaminants that have been aged for the
      duration of the experiment together in the soil. Desorption dynamics are compared
      in co-contaminant and single-PAH contaminated spiked soils to demonstrate the
      occurrence of competitive displacement. Overall, a single HPCD-extraction
      technique proved accurate and reproducible for the estimation of PAH
      bioavailability from soil.

PMID- 16564119
TI  - Simultaneous presence of DDT and pyrethroid residues in human breast milk from a
      malaria endemic area in South Africa.
AB  - DDT and pyrethroids were determined in 152 breast-milk samples from three towns
      in KwaZulu-Natal, South Africa, one of which had no need for DDT for malaria
      control. All compounds were found present in breast milk. Primiparae from one
      town had the highest mean SigmaDDT whole milk levels (238.23 microg/l), and
      multiparae from the same town had the highest means for permethrin (14.51
      microg/l), cyfluthrin (41.74 microg/l), cypermethrin (4.24 microg/l),
      deltamethrin (8.39 microg/l), and Sigmapyrethroid (31.5 microg/l), most likely
      derived from agriculture. The ADI for DDT was only exceeded by infants from one
      town, but the ADI for pyrethroids was not exceeded. Since the ADI for DDT was
      recently reduced from 20 to 10 microg/kg/bw, we suggest that this aspect be
      treated with concern. We therefore raise a concern based on toxicant
      interactions, due to the presence of four different pyrethroids and DDT.
      Breastfeeding however, remains safe under prevailing conditions.

PMID- 16564120
TI  - Polybrominated diphenyl ethers in South China maternal and fetal blood and breast
      milk.
AB  - Twenty-one-paired human fetal and maternal serum and 27 breast milk samples at
      South China were analyzed for concentrations of polybrominated diphenyl ethers
      (PBDEs). Seven PBDE congeners (BDE-28, -47, -99, -100, -153, -154, and -183) were
      quantified using gas chromatography/mass spectrometry (GC/MS). This is the first
      report to present the residue levels of PBDEs in human samples of China. The
      concentrations of total PBDEs ranged from 1.5 to 17 ng/g in the samples and were
      within the range reported in European samples for a similar population, but lower
      than human tissue levels in North America. BDE-47 and -153 were the dominant PBDE
      congeners in all samples and accounted for 60% of the total PBDEs. Further
      research is needed to determine the exposure route of PBDEs and their health
      effects.

PMID- 16564121
TI  - A history of the Collegium Internationale Neuro-Psychopharmacologicum (1957
      2004).
AB  - Recognition that one of the essential prerequisites of successful neuro
      psychopharmacological research is a continuous dialogue between clinicians and
      basic scientists led to the founding of the Collegium Internationale Neuro
      Psychopharmacologicum (CINP) in Zurich on September 2, 1957. At the time, CINP
      was the only association in neuro-psychopharmacology. It was hoped that by
      organizing biennial congresses, it would facilitate the interaction among the
      many disciplines involved in the new field. It was also envisaged that discussion
      of findings in translational research would provide guidance for developing more
      selective and thereby more effective psychotropic drugs. These expectations were
      not fulfilled. In the years that followed, major developments in
      neuropharmacology without parallel development in the methodology of clinical
      investigations, created a widening gap between neuro- and psychopharmacology.
      Clinical interpretations of neuropharmacological findings filled in the missing
      information from translational research. In the 1980s, to facilitate the
      dissemination of these interpretations, CINP established Travel Awards for Young
      Investigators to assist them in attending the biennial meetings. In the 1990s,
      the college extended its activities by organizing other meetings, including
      president's workshops, regional meetings, educational seminars and other
      programs. By the end of the 20th century CINP was a legal entity that was
      registered in Switzerland with domicile in Zurich. It had also become a
      financially secure organization with sufficient funds to support administration
      and coordination. In the early years of the 21st century CINP established a
      central office and a congress-organizing group. To meet the needs of its steadily
      growing membership from Asia, Australia and the Latin Americas, CINP has been
      regionalized. In order to regain its relevance to all its members it is hoped
      that CINP will return to its roots.

PMID- 16564122
TI  - S-adenosylmethionine but not glutathione protects against galactosamine-induced
      cytotoxicity in rat hepatocyte cultures.
AB  - A gradual but extensive depletion of hepatic GSH has long been known to accompany
      development of galactosamine-induced hepatotoxicity in rats, and some protection
      from liver injury has been observed after administration of sulfhydryl-donating
      compounds. Although these observations support a key role for GSH in the
      underlying mechanism, the impact of GSH depletion and repletion on the
      hepatotoxic response to galactosamine is unclear. To investigate the role of GSH
      in galactosamine-induced liver injury, we examined the effect of modulating GSH
      content on galactosamine toxicity in rat primary hepatocyte cultures.
      Galactosamine (4 mM) cytotoxicity was assessed by release of lactate
      dehydrogenase into the culture medium, and hepatocellular GSH content was
      measured by HPLC with electrochemical detection. The data indicated that prior
      depletion of GSH with either diethyl maleate or buthionine sulfoximine
      significantly enhanced galactosamine toxicity; however, addition of GSH-ester or
      alternate sulfur nucleophiles at various times during the incubation did not
      abrogate toxicity. In contrast, co-addition of S-adenosylmethionine (SAMe) with
      galactosamine exerted a marked protective effect without significantly altering
      hepatocyte GSH content. These data suggest that GSH depletion is not directly
      involved in the sequelae for galactosamine-induced hepatotoxicity, and raise the
      possibility that SAMe may have hepatoprotective effects that are not dependent on
      its ability to enhance GSH synthesis.

PMID- 16564123
TI  - New airways for resuscitation?
AB  - Over the last 15 years supraglottic airway devices (SADs), most notably the
      classic laryngeal mask airway (LMA) have revolutionised airway management in
      anaesthesia. In contrast for resuscitation, both in and outside hospital,
      facemask ventilation and tracheal intubation remain the mainstays of airway
      management. However there is evidence that both these techniques have
      complications and are often poorly performed by inexperienced personnel. Tracheal
      intubation also has the potential to cause serious harm or death through
      unrecognised oesophageal intubation. SADs may have a role in airway management
      for resuscitation as first responder devices, rescue devices or for use during
      patient extraction. In particular they may be beneficial as the level of skill
      required to use the device safely may be less than for the tracheal tube.
      Concerns have been expressed over the ability to ventilate the lungs successfully
      and also the risk of aspiration with SADs. The only SADs recommended by ILCOR in
      its current guidance are the classic LMA and combitube. Several SADs have
      recently been introduced with claims that ventilation and airway protection is
      improved. This pragmatic review examines recent developments in SAD technology
      and the relevance of this to the potential for using SADs during resuscitation.
      In addition to examining research directly related to resuscitation both on bench
      models and in patients the review also examines evidence from anaesthetic
      practice. SADS discussed include the classic, intubating and Proseal LMAs, the
      combitube, the laryngeal tube, laryngeal tube sonda mark I and II and single use
      laryngeal masks.

PMID- 16564124
TI  - Placenta praevia percreta with silent uterine incomplete rupture complicated with
      puerperal haemolytic-uremic syndrome.

PMID- 16564125
TI  - Transforming growth factor beta and platelet-derived growth factor in human
      myometrium and in uterine leiomyomas at various stages of tumour growth.
AB  - OBJECTIVE: Some authors suggest that growth factors are intermediate regulatory
      elements through which the ovarian hormones exert their growth-stimulatory
      effects on uterine leiomyomas. STUDY DESIGN: It was decided to compare the
      amounts of transforming growth factor beta (TGF-beta) and platelet-derived growth
      factor (PDGF) in myometrium and in uterine leiomyomas of various weights (small:
      less than 10 g and large: more than 100 g). The tissues were homogenised and
      extracted with 1M acetic acid or with 0.05 M Tris-HCl, pH 7.6. The extracts were
      assayed for TGF-beta and PDGF with the use of the ELISA technique. RESULTS: The
      Tris-HCl was more efficient at extracting solvent than 1M of acetic acid. Both
      myometrium and leiomyomas contained nanogram amounts of extractable TGF-beta and
      picogram amounts of PDGF. Western immunoblotting demonstrated that both factors
      exist as stable complexes, probably with extracellular matrix components. The
      PDGF/TGF-beta ratio in Tris-HCl extracts was higher in leiomyomas than in
      myometrium and it increased during tumour growth. CONCLUSION: It is known that
      low concentrations of TGF-beta induce proliferation of cells by stimulating
      autocrine PDGF secretion. Higher concentrations of TGF-beta1 evoke a reverse
      effect by the down-regulation of the PDGF receptor and by direct growth
      inhibition. The increase in the PDGF/TGF-beta ratio during tumour growth seems be
      important in tumour biology. The low amount of TGF-beta eliminates the inhibitory
      effect of this factor on cell proliferation and stimulates both autocrine PDGF
      secretion and promotes the synthesis of PDGF receptors. It is thus possible to
      bind more PDGF by myometrial cells resulting in a hyperplasia of myometrium and
      enhancement of extracellular matrix synthesis.

PMID- 16564126
TI  - Prescribing all phosphodiesterase 5 inhibitors to a patient with erectile
      dysfunction--a realistic and feasible option in everyday clinical practice-
      outcomes of a simple treatment regime.
AB  - OBJECTIVE: In clinical practice, to apply and evaluate outcomes of a treatment
      regime, in which the patient had the opportunity to try all the available
      phosphodiesterase 5 (PDE5) inhibitors. METHODS: Patients eligible for treatment
      with PDE5 inhibitors were prescribed 8 tablets with a shorter-acting substance
      (four tablets sildenafil 100mg and four tablets vardenafil 20mg) and eight
      tablets with a long-acting substance (tadalafil 20mg). Outcomes of the regime
      were recorded. RESULTS: Of the 186 patients, 64 (34%) had not been treated
      previously (naive), and 122 (66%) were undergoing treatment for their erectile
      dysfunction. The overall treatment response was 89% (165 of 186 patients); 78%
      (n=145 of 186 patients) tested all three substances. No significant difference in
      choice between long- and shorter-acting medications in the overall material was
      observed. Two thirds of the naive patients (n=64) preferred a shorter-acting
      substance (p<0.01). Every fifth man requested both a shorter- and a long-acting
      medication to accommodate his need. CONCLUSION: If patients are given the
      opportunity in clinical practice to try all three available PDE5 inhibitors, the
      overall response rate is very high, almost 90%. No significant difference in
      patient preference between long- and shorter-acting drugs was observed. Treatment
      choice was based mainly on efficacy or duration of effect.

PMID- 16564127
TI  - Treatment strategy for "non-responders" to tadalafil and vardenafil: a real-life
      study.
AB  - OBJECTIVES: To develop and test step-wise treatment strategy for erectile
      dysfunction "non-responders" to tadalafil and vardenafil. MATERIAL AND METHODS:
      Two groups [tadalafil-treated (TG); vardenafil-treated (VG)] of 100 consecutive
      patients complaining of non-response to treatments were enrolled in three-phase
      study. Phase 1: inadequate use was identified and patients were rechallenged,
      after receiving detailed usage information. Phase 2: true non-responders were
      given new instructions based on drugs' pharmacologic profiles: TGs were dosed at
      least 2 h before intercourse; VGs were dosed only in fasted state. Remaining non
      responders entered phase 3: continuous administration of 20 mg tadalafil every
      other day, or 20 mg vardenafil every day for 2 weeks. Efficacy was based on
      positive (yes) response to two questions: "Were your erections rigid, and did
      they last long enough to have successful intercourse?" and "Do you want to repeat
      your prescription?" RESULTS: Tadalafil group: Inappropriate use was recognized in
      32 patients; 14 (43.75%) responded after adequate instruction. Phase 2: 32 of 86
      (37.2%) had intercourse at least 2 h after dose intake. Phase 3: 6 of 86 (11.1%)
      responded to continuous administration. Overall salvage rate was 52 of 100 (52%).
      Vardenafil group: Inappropriate use was recognized in 38 patients; 12 (31.58%)
      responded after adequate instruction. Phase 2, 22 of 88 (25%) responded to dosing
      in a fasted state. Phase 3: 12 of 66 (18.2%) responded to daily dosing. Overall
      salvage rate was 46 of 100 (46%). CONCLUSIONS: Following proposed treatment
      strategy may maximize response rate to phosphodiesterase 5 inhibitors;
      appropriate usage instructions may play significant role in response rate.

PMID- 16564128
TI  - Failed hypospadias repair presenting in adults.

PMID- 16564130
TI  - Analytical solutions of the first three frequency shifts of AFM non-uniform probe
      subjected to the Lennard-Jones force.
AB  - The role of higher cantilever modes is important to obtain some material
      contrast. The analysis of AFM subjected to a short-range force can improve
      greatly the studies of surface topography and interaction energies and
      interaction forces, especially for chemical and biological materials. When the
      tip-sample distance is in the order of inter-atomic spacing, the short-range tip
      sample force is usually simulated by the Lennard-Jones model. In this study, the
      analytical method to determine the frequency shift of AFM subjected to the
      Lennard-Jones force is proposed. The closed-form solution of the partial
      differential equation with a nonlinear boundary condition is derived and then the
      corresponding frequency shifts of higher modes can be determined easily.
      Moreover, the conventional perturbation method is usually used to determine the
      frequency shift, but only for the first mode. This is because the original
      continuous beam system is transformed into a discrete lumped-masses model.
      Although the above disadvantages exist, the lumped-masses model is simple and
      intuitive. Using the principle of dynamic strain energy, the conventional
      perturbation method is revised successfully to determine the frequency shifts of
      higher modes. The assessment of the generalized perturbation method and the
      proposed method is made. Finally, the effects of several parameters on the first
      three frequency shifts are investigated.

PMID- 16564129
TI  - Psychobiologic correlates of the metabolic syndrome and associated sexual
      dysfunction.
AB  - OBJECTIVES: The association of low testosterone level and erectile dysfunction
      (ED) with metabolic syndrome (MS) is receiving increasing attention. The present
      study determined the psychobiologic characteristics of sexual dysfunction (SD)
      associated with MS (as defined by the National Cholesterol Education Program's
      Adult Treatment Panel III criteria) in a series of 803 consecutive male
      outpatients. METHODS: Several hormonal, biochemical, and instrumental (penile
      Doppler ultrasound [PDU]) parameters were studied, along with general
      psychopathology scores (Middlesex Hospital Questionnaire modified [MHQ]). The
      Structured Interview on Erectile Dysfunction (SIEDY) was also applied. RESULTS:
      Among the 236 patients (29.4%) diagnosed as having a MS, 96.5% reported ED, 39.6%
      hypoactive sexual desire (HSD), 22.7% premature ejaculation, and 4.8% delayed
      ejaculation. Patients with MS were characterised by greater subjective (as
      assessed by SIEDY) and objective (as assessed by PDU) ED and by greater somatised
      anxiety than the rest of the sample. The prevalence of overt hypogonadism (total
      testosterone <8 nM) was significantly higher in patients with MS. Among MS
      components, waist circumference and hyperglycaemia were the best predictors of
      hypogonadism. Hypogonadal patients with MS showed higher gonadotropin and lower
      free testosterone levels, suggesting a primary hypogonadism. Among patients with
      MS, hypogonadism was present in 11.9% and 3.8% in the rest of the sample
      (p<0.0001) and was associated with typical hypogonadism-related symptoms, such as
      hypoactive sexual desire, low frequency of sexual intercourse, and depressive
      symptoms. CONCLUSIONS: Our data suggest that MS is associated with a more severe
      ED and induces somatisation. Furthermore, MS is associated with a higher
      prevalence of hypogonadism in patients with SD. The presence of hypogonadism can
      further exacerbate the MS-associated sexual dysfunction, adding the typical
      hypogonadism-related symptoms (including HSD, 66.7%). Recognising MS associated
      with hypogonadism is important for both sexual and general health and its serious
      potential associated risks.

PMID- 16564131
TI  - Incidence of Neospora caninum and other intestinal protozoan parasites in
      populations of Swiss dogs.
AB  - The protozoan parasite Neospora caninum is one of the most important
      abortifacient organisms in cattle worldwide. The dog is known to act as
      definitive host although its potential role as infection source for bovines still
      remains unelucidated. The aim of the present study was to compile initial
      epidemiological data on the prevalence and incidence of N. caninum in Swiss dogs
      acting as definitive hosts. Thus, 249 Swiss dogs were investigated
      coproscopically in monthly intervals over a period of 1 year. A total of 3289
      fecal samples was tested by the flotation technique. Among these, 202 were shown
      to contain Sarcocystis sp. (6.1%), 149 Cystoisospora sp. (=Isospora sp.; 4.5%)
      and 25 Hammondia/Neospora-like oocysts (HNlO) (0.7%). All but one sample
      containing HNlO were from different dogs; one dog shed HNlO at two subsequent
      time points. Calculation of the yearly incidence for HNlO resulted in the
      surprisingly high value of 9.2%. Farm dogs exhibited a higher incidence for HNlO
      than urban family dogs. Thirteen out of the 25 HNlO-samples showed sporulation
      after 5 days incubation at room temperature. HNlO were further differentiated by
      species-specific PCR. However, all HNlO-samples were negative for N. caninum,
      Hammondia heydorni and Toxoplasma gondii. One reason may be the low oocyst
      density found in most fecal samples, which did not permit us to carry out PCR
      under optimal conditions. Three out of the 25 HNlO-cases contained enough oocysts
      to allow further enrichment and purification by the flotation technique.
      Subsequently, twenty to fifty sporulated HNlO-oocysts were orally administered to
      Meriones unguiculatus. All gerbils were seronegative for N. caninum at 5 weeks
      p.i. A N. caninum-seroprevalence of 7.8% was determined by ELISA upon 1132 serum
      samples collected from dogs randomly selected by veterinarians among their
      clinical patients.

PMID- 16564132
TI  - Sericea lespedeza hay as a natural deworming agent against gastrointestinal
      nematode infection in goats.
AB  - Infection with gastrointestinal nematodes (GIN), particularly Haemonchus
      contortus, is the biggest constraint to profitable goat production in the United
      States (US). Due to widespread prevalence of anthelmintic resistance in goat GIN,
      alternative, non-chemical control methodologies are needed to increase
      profitability of small ruminant industries. A study was designed to test the
      efficacy of a high condensed tannin (CT) legume, sericea lespedeza [SL, Lespedeza
      cuneata (Dum.-Cours. G. Don)] against GIN of goats fed in confinement. The goats
      were given a trickle infection of 500 H. contortus larvae/animal three times per
      week during the trial to simulate natural infection. Twenty Boer bucks (6-8
      months old) were fed bermudagrass [BG, Cynodon dactylon (L.) Pers.] hay plus
      concentrate for 5 weeks in confinement and then 10 animals were switched to SL
      hay for an additional 7 weeks. Throughout the trial, feces and blood were
      collected weekly from individual animals to determine fecal egg count (FEC) and
      blood packed cell volume (PCV). Fecal cultures were made weekly from pooled
      samples to determine treatment effects on GIN larval development. All goats were
      slaughtered at the end of the trial, with adult worms in the abomasum and small
      intestine of each goat recovered, counted, and identified to species. Feeding SL
      hay to goats significantly (P<0.01) reduced FEC and increased PCV compared with
      BG hay. In addition, a lower percentage of ova in feces from SL-fed goats
      developed into infective (L3) larvae. There was a direct effect of SL hay on
      adult worms, with significantly (P<0.01) lower numbers of both abomasal (H.
      contortus, Teladorsagia circumcincta) and small intestinal (Trichostrongylus
      colubriformis) nematodes compared with goats fed BG hay. Feeding SL hay to goats
      is an effective means of controlling parasitic nematodes and may be a potential
      supplement/replacement for chemical anthelmintics.

PMID- 16564133
TI  - Expression of hyaluronan synthase genes in umbilical cord blood stem/progenitor
      cells.
AB  - Scientific progress reveals an ever-expanding role of hyaluronan (HA) in diverse
      biological functions. It has become increasingly clear that HA might also be
      essential for certain functions of stem cells. CD133+ cells isolated from
      umbilical cord blood (UCB) seem to represent an alternative to CD34+ cells as a
      source of transplantable haematopoietic progenitor cells. The aim of this study
      was to investigate expression patterns of hyaluronan synthases (HAS) genes in
      freshly isolated and cultured UCB progenitor cells and to compare HAS mRNA levels
      to those found in non-progenitor cells. CD133+ stem cells were isolated from UCB
      using an immunomagnetic procedure. Investigation of HAS mRNA expression patterns
      in CD133+ and CD133- cells by RT-PCR was performed immediately after isolation as
      well as after cultivation towards myelomonocytic lineage. In addition, activation
      patterns of mitogen activated protein kinases (MAPK) were analyzed by Western
      blot experiments. mRNA for HAS1 is undetectable but HAS3 mRNA can be readily
      detected in freshly isolated CD133+ as well as in CD133- UCB cells. More
      importantly, our data demonstrate that mRNA for HAS2 can only be detected in
      CD133+ progenitor cells. In addition, while MAPK are slightly activated in CD133-
      UCB cells, no significant phosphorylation of MAPK could be observed in CD133+
      cells, excluding a role of these kinases in the regulation of HAS2. HAS2 is
      expressed only in freshly isolated CD133+ cells and quickly diminishes during
      differentiation. Because of this, HAS2 gene expression might be suitable as a new
      marker for CD133+ UCB-derived stem cells.

PMID- 16564134
TI  - Involvement of the AtoS-AtoC signal transduction system in poly-(R)-3
      hydroxybutyrate biosynthesis in Escherichia coli.
AB  - The AtoS-AtoC signal transduction system in E. coli, which induces the atoDAEB
      operon for the growth of E. coli in short-chain fatty acids, can positively
      modulate the levels of poly-(R)-3-hydroxybutyrate (cPHB) biosynthesis, a
      biopolymer with many physiological roles in E. coli. Increased amounts of cPHB
      were synthesized in E. coli upon exposure of the cells to acetoacetate, the
      inducer of the AtoS-AtoC two-component system. While E. coli that overproduce
      both components of the signal transduction system synthesize higher quantities of
      cPHB (1.5-4.5 fold), those that overproduce either AtoS or AtoC alone do not
      display such a phenotype. Lack of enhanced cPHB production was also observed in
      cells overexpressing AtoS and phosphorylation-impaired AtoC mutants. The results
      were not affected by the nature of the carbon source used, i.e., glucose, acetate
      or acetoacetate. An E. coli strain with a deletion in the atoS-atoC locus (delta
      atoSC) synthesized lower amounts of cPHB compared to wild-type cells. When the
      delta atoSC strain was transformed with a plasmid carrying a 6.4-kb fragment
      encoding the AtoS-AtoC system, cPHB biosynthesis was restored to the level of the
      atoSC+ cells. Introduction of a multicopy plasmid carrying a functional atoDAEB
      operon, but not one with a promoterless operon, resulted in increased cPHB
      synthesis only in atoSC+ cells in the presence of acetoacetate. These results
      indicate that the presence of both a functional AtoS-AtoC two-component signal
      transduction system and a functional atoDAEB operon is critical for the enhanced
      cPHB biosynthesis in E. coli.

PMID- 16564135
TI  - Bioinformatics for comprehensive finding and analysis of glycosyltransferases.
AB  - Bioinformatics is a very powerful tool in the field of glycoproteomics as well as
      genomics and proteomics. As a part of the Glycogene Project (GG project), we have
      developed a novel bioinformatics system for the comprehensive identification and
      in silico cloning of human glycogenes. Using our system, a total of 105 candidate
      human glycogenes were identified and then engineered for heterologous expression.
      Of these candidates, 38 recombinant proteins were successfully identified for
      their enzyme activity and substrate specificity. We also classified 47 out of 60
      carbohydrate-active enzyme glycosyltransferase families into 4 superfamilies
      using the profile Hidden Markov Model method. On the basis of our classification
      and the relationship between glycosylation pathways and superfamilies, we propose
      the evolution of glycosyltransferases.

PMID- 16564136
TI  - Carbohydrates as future anti-adhesion drugs for infectious diseases.
AB  - Adhesion of pathogenic organisms to host tissues is the prerequisite for the
      initiation of the majority of infectious diseases. In many systems, it is
      mediated by lectins present on the surface of the infectious organism that bind
      to complementary carbohydrates on the surface of the host tissues. Lectin
      deficient mutants often lack the ability to initiate infection. The bacterial
      lectins are typically in the form of elongated submicroscopic multi-subunit
      protein appendages, known as fimbriae (or pili). The best characterized of these
      are the mannose-specific type 1 fimbriae, the galabiose-specific P fimbriae and
      the N-acetylglucosamine-specific fimbriae of Escherichia coli. Soluble
      carbohydrates recognized by the bacterial surface lectins block the adhesion of
      the bacteria to animal cells in vitro. Aromatic alpha-mannosides are potent
      inhibitors of type 1 fimbriated E. coli, being up to 1000 times more active than
      MealphaMan, with affinities in the nanomolar range. This is due to the presence
      of a hydrophobic region next to the monosaccharide-binding site of the fimbriae,
      as recently demonstrated by X-ray studies. Polyvalent saccharides (e.g.,
      neoglycoproteins or dendrimers) are also powerful inhibitors of bacterial
      adhesion in vitro. Very significantly, lectin-inhibitory saccharides have been
      shown to protect mice, rabbits, calves and monkeys against experimental infection
      by lectin-carrying bacteria. Since anti-adhesive agents do not act by killing or
      arresting the growth of the pathogens, it is very likely that strains resistant
      to such agents will emerge at a markedly lower rate than of strains that are
      resistant to antibiotics. Suitable sugars also inhibit the binding to cells of
      carbohydrate-specific toxins, among them those of Shigella dysenteriae Type 1,
      and of the homologous Verotoxins of E. coli, specific for galabiose.
      Appropriately designed polyvalent ligands are up to six orders of magnitude
      stronger inhibitors of toxin binding in vitro than the monovalent ones, and they
      protect mice against the Shigella toxin. The above data provide clear proof for
      the feasibility of anti-adhesion therapy of infectious diseases, although this
      has not yet been successful in humans. All in all, however, there is little doubt
      that inhibitors of microbial lectins will in the near future join the arsenal of
      drugs for therapy of infectious diseases.

PMID- 16564137
TI  - Tobacco use among medical professionals in Kerala, India: the need for enhanced
      tobacco cessation and control efforts.
AB  - In developing nations where reductions in tobacco use have not been realized, it
      is critical that health professionals be encouraged to abstain from tobacco use.
      Data on tobacco use among health professionals in India are limited. We conducted
      cross-sectional surveys among 110 male medical school faculty (MSF), 229
      physicians (67% male), 1130 medical students (46% male), and 73 female nursing
      students. Information on tobacco use and quit attempts was collected using
      structured questionnaires. Among the male respondents, current smokers were 15.1%
      of MSF, 13.1% of physicians, and 14.1% of medical students. Among current
      smokers, 42% of MSF and physicians and 51% of medical students had not attempted
      quitting in the last year. However, one third of MSF and physicians and 16% of
      medical students had attempted to quit at least 4 times. This is one of the first
      studies among health care professionals in India. Our findings show that a
      substantial proportion of physicians and medical students in Kerala continue to
      smoke. Smoking cessation programs are warranted in medical schools in Kerala. An
      initiative is presently underway by the authors to incorporate tobacco education
      into the medical school curriculum.

PMID- 16564138
TI  - Postnatal hypokinesia and the delayed time frame of sudden infant death syndrome.
AB  - The sudden infant death syndrome peaks in the second and third month of life.
      This is the period of the "two-month transformation of the central nervous
      system" in the human infant. Studies of 120 days of imposed hypokinesia in man
      demonstrated that the maximum period of autonomic dysfunction was delayed until
      the beginning of the second month through to the fourth month of the experiment.
      Hypokinesia also impaired sleep mechanisms and induced polymorphic changes in
      almost all systems of the human body. These studies suggest that prolonged
      postnatal hypokinesia in infants may induce autonomic dysfunction in the CNS,
      especially during the "two-month transformation period" of major postnatal neural
      development.

PMID- 16564139
TI  - Solitary luteinized follicle cyst of pregnancy and puerperium.
AB  - We report a huge ovarian solitary luteinized follicle cyst (SLFC) that contained
      17 liters of fluid. Computed tomography scan revealed a 32 x 32 x 20 cm right
      simple cystic ovarian mass without calcification or septation. The fluid was
      removed, and the collapsed unilocular cyst was examined pathologically. No solid
      or papillary areas were identified. The cyst wall lining was composed of multiple
      layers of luteinized cells of variable size and shape with abundant eosinophilic
      cytoplasm and focally enlarged, pleomorphic, and hyperchromatic nuclei. Nests of
      luteinized cells were embedded within the fibrous tissue of the cyst wall. These
      findings are characteristic of solitary luteinized follicle cyst of pregnancy.
      Even though less than 15 cysts of this kind have been recorded, one should
      consider this uncommon, benign, non-neoplastic cystic ovarian lesion in the
      differential diagnosis of other cystic ovarian lesions.

PMID- 16564140
TI  - Follicular dendritic cell tumor of the gastrointestinal tract: Report of a rare
      neoplasm and literature review.
AB  - Follicular dendritic cell (FDC) tumor is a rare neoplasm of the accessory immune
      system showing FDC differentiation. Histologically, a conventional type and an
      inflammatory pseudotumor (IPT-like) type are recognized. The etiology of FDC
      tumor is unknown. While rare FDC tumors were associated with hyaline-vascular
      Castleman's disease (HVCD), hepatosplenic IPT-like FDC tumors consistently harbor
      EBV infection. FDC tumors of the gastrointestinal (GI) tract and
      mesentery/omentum are exceedingly rare, with only 17 cases reported so far. We
      report an additional case of an IPT-like FDC tumor of the ileum and mesentery in
      a 52-year-old schizophrenic man. The tumor consisted of highly atypical
      multinucleated giant cells in a background of intense lymphoid infiltrate with
      prominent eosinophilia reminiscent of Hodgkin's lymphoma. Tumor cells were
      immunoreactive for vimentin, CD21, CD35, fascin, smooth muscle actin and CD68,
      but were negative for all lineage-specific lymphoreticular, myeloid, mesenchymal
      and epithelial markers. Immunostaining for HHV-8 and in situ hybridization for
      EBV-encoded RNA (EBER) were negative. Some mesenteric lymph nodes showed HVCD
      like changes. The differential diagnostic considerations of this unusual and rare
      neoplasm, mainly lymphocyte-rich GI stromal tumor (GIST), malignant lymphoma and
      inflammatory neoplasia of diverse histogenetic types, will be discussed together
      with a literature review on gastrointestinal FDC tumors.

PMID- 16564141
TI  - Development of opioid formulations with limited diversion and abuse potential.
AB  - Non-medical abuse of prescription opioid medications is not a new phenomenon, but
      such use has been increasing in recent years. Various methods have been used and
      continue to be developed in an effort to limit diversion and abuse of opioid
      medications. A number of these methods will be described for opioid analgesic and
      addiction treatment formulations using relevant historical examples (e.g.
      propoxyphene, pentazocine, buprenorphine) as well as examples of formulations
      currently being considered or under development (e.g. oxycodone plus naltrexone,
      sustained-release buprenorphine). The focus, though not exclusively, will be on
      those formulations that represent a combination of an opioid agonist with an
      antagonist. These methods must take into consideration the pharmacokinetic
      profile of the agonist and antagonist, the expected primary route of abuse of the
      medication and the medication combination, the dose of medication that is likely
      to be abused, the availability of alternative drugs of abuse, and the population
      of potential abusers that is being targeted with the revised formulation.

PMID- 16564142
TI  - Plum pox virus induces differential gene expression in the partially resistant
      stone fruit tree Prunus armeniaca cv. Goldrich.
AB  - We investigated the changes in the expression profiles of the partially resistant
      apricot (Prunus armeniaca L.) cultivar Goldrich following inoculation with Plum
      pox virus (PPV) using cDNA-amplification fragment length polymorphism (AFLP).
      Altered expression patterns were detected and twenty-one differentially expressed
      cDNA had homologies with genes in databases coding for proteins involved in
      metabolism, signal transduction, defense, stress and intra/intercellular
      connections. Seven of the modified expressed patterns were further investigated
      by semi-quantitative RT-PCR or Northern blotting. The expression patterns of five
      of these genes were confirmed in the partially resistant P. armeniaca cv.
      'Goldrich' and assessed in a susceptible genotype. One of these cDNAs, coding for
      a putative class III chitinase, appeared to be repressed in infected plants of
      the partially resistant genotype and expressed in the susceptible one which could
      be related to the partially resistant phenotype. On the contrary, the expression
      patterns of the genes coding for a transketolase, a kinesin-like and an ankyrin
      like protein, were clearly linked to the susceptible interaction. These candidate
      genes could play a role either in the compatible interaction leading to virus
      invasion or to the quantitative resistance of apricot to PPV.

PMID- 16564143
TI  - Prediction of non-coding and antisense RNA genes in Escherichia coli with Gapped
      Markov Model.
AB  - A new mathematical index was developed to identify and characterize non-coding
      RNA (ncRNA) genes encoded within the Escherichia coli (E. coli) genome. It was
      designated the GMMI (Gapped Markov Model Index) and used to evaluate sequence
      patterns located at the separate positions of consensus sequences, codon biases
      and/or possible RNA structures on the basis of the Markov model. The GMMI was
      able to separate a set of known mRNA sequences from a mixture of ncRNAs including
      tRNAs and rRNAs. Consequently, the GMMI was employed to predict novel ncRNA
      candidates. At the beginning, possible transcription units were extracted from
      the E. coli genome using consensus sequences for the sigma70 promoter and the rho
      independent terminator. Then, these units were evaluated by using the GMMI. This
      identified 133 candidate ncRNAs, which contain 29 previously annotated small RNA
      genes and 46 possible antisense ncRNAs. Furthermore 12 transcripts (including
      five antisense RNAs) were confirmed according to the expression analysis. These
      data suggests that the expression of small antisense RNAs might be more common
      than previously thought in the E. coli genome.

PMID- 16564144
TI  - Facilitated skin penetration of lidocaine: combination of a short-term
      iontophoresis and microemulsion formulation.
AB  - The objective of this study was to demonstrate the potential of the application
      of a short-term iontophoresis on the topical delivery of lidocaine hydrochloride
      from a microemulsion-based system. Five- and 10-min durations of anodal
      iontophoresis applied onto porcine skin were examined in combination with a
      microemulsion containing 2.5% lidocaine hydrochloride. A similar combination (10
      min iontophoresis with microemulsion in the anodal electrode) was also examined
      in vivo in a rat model. It was shown in vitro that by combining microemulsion
      application with a 10-min iontophoresis of 1.13 mA/cm2 electric current density,
      a significantly increased flux was obtained compared with a combination of
      aqueous drug solution with the same iontophoresis protocol. In vivo studies
      revealed that 57.71 +/- 18.65 and 18.43 +/- 9.17 microg cm(-2) were reached in
      the epidermis and dermis, respectively, at t = 30 min of microemulsion
      application, when iontophoresis was applied for 10 min. In contrast, the
      application of aqueous solution-iontophoresis resulted in a relatively lower drug
      accumulation (21.44 +/- 10.42 and 5.30 +/- 2.25 microg cm(-2) in the epidermis
      and dermis, respectively, at t = 30) with more rapid clearance of the drug from
      the skin. Ten-minute application of a low-current electric field on a new topical
      microemulsion appears to make significant changes in skin permeability. The
      potential advantages of this procedure include significantly increased flux,
      accumulation of a large skin drug depot, short lag times, reduced irritation
      (compared to long-term iontophoresis), simplicity and ease of compliance.

PMID- 16564145
TI  - Ginsenoside Re attenuate beta-amyloid and serum-free induced neurotoxicity in
      PC12 cells.
AB  - AIM: To study the effect of ginsenoside Re on PC12 cell damage induced by serum
      deprivation and beta-amyloid peptide. METHODS: PC 12 cell survival was measured
      by MTT and lactate dehydrogenase (LDH) assay. Results Serum-free medium and beta
      amyloid peptide (10-100 microM) induced cytotoxicity in PC 12 cells. Ginsenoside
      Re (0.1-100 microM) attenuated the cytotoxic effects of serum-free medium and
      beta-amyloid peptide (50 microM) in a concentration-dependent manner. CONCLUSION:
      Ginsenoside Re prevented PC 12 cells from lesion induced by serum-free medium and
      beta-amyloid peptide.

PMID- 16564146
TI  - Polymorphism of four X-chromosomal STRs: DXS7423, DXS7424, DXS8378 and DXS6809 in
      a North Italian population sample and their use in kinship testing.
AB  - The present study analyses three tetranucleotide (DXS7423, DXS8378, DXS6809) and
      one trinucleotide (DXS7424) X-linked STRs loci in a population sample of North
      Italy to evaluate their efficiency in forensic applications. The four loci were
      also used to solve a case of deficiency paternity, in which the question was to
      establish whether two women were half sisters.

PMID- 16564147
TI  - Fatal occupational inhalation of hydrogen sulfide.
AB  - A young man aged 22 years, a sewer worker by profession, died after massive
      inhalation of hydrogen sulfide while at work. He was rescued by the emergency
      services and admitted to the critical care department, where he died due to
      massive myocardial necrosis less than 24 h after admission. In this case, where
      the causes of the accident were not clearly established, autopsy and
      anatomopathologic examination made it possible to confirm the causal lesions
      which resulted in death and to question the initial version of the circumstances
      of the accident. Medicolegal investigation was valuable in determining possible
      liabilities and repercussions on coverage as an industrial accident by the
      national health insurance system.

PMID- 16564148
TI  - Evaluation of the role of abstinence in heroin overdose deaths using segmental
      hair analysis.
AB  - In the body heroin is rapidly metabolized to 6-acetylmorphine and morphine.
      Victims of lethal heroin overdose often present with fairly low blood
      concentrations of morphine. Reduced tolerance due to abstinence has been proposed
      to account for this finding. The aim of the present study was to examine the role
      of abstinence in drug-related deaths by comparing recent and past exposure to
      opioids using segmental hair analysis with the postmortem blood morphine
      concentrations in deceased heroin users. The study included 60 deceased drug
      addicts in the Stockholm area, Sweden. In 32 cases, death was not related to
      heroin intake. In 18 of the 28 heroin fatalities, opioids were absent in the most
      recent hair segment, suggesting a reduced tolerance to opioids. However, the
      blood morphine levels were similar to those found in the 10 subjects that showed
      continuous opioid use. Hair and blood analysis disclosed an extensive use of
      additional drugs that directly or indirectly may influence the opioid system. The
      results suggest that abstinence is not a critical factor for heroin overdose
      death. Obviously tolerant subjects die after intake of similar doses. Other
      factors, particularly polydrug use, seem to be more causally important for these
      deaths.

PMID- 16564149
TI  - Age related changes in the activity-rest circadian rhythms and c-fos expression
      of ring doves with aging. Effects of tryptophan intake.
AB  - Age related changes in the circadian rhythms and sleep quality has been linked
      with impairment in the function of the suprachiasmatic nucleus (SCN) and
      melatonin secretion. The precursor of melatonin, serotonin (5-HT) is a
      neurotransmitter involved in the synchronisation of the circadian clock located
      in SCN, which shows decreased levels with age. The present work studied the
      effects of L-tryptophan, the precursor of 5-HT, on the circadian activity-rest
      rhythm and c-fos expression in the SCN of young and old ring doves, animals
      diurnal and monocyclic as humans. Two hours before the onset of dark phase,
      animals housed in cages equipped for activity recording and maintained under
      12/12 L/D conditions, received orally L-tryptophan (100 and 240 mg/kg) and, for
      comparative purposes, melatonin (2.5 and 5 mg/kg). The administration of both L
      tryptophan and melatonin reduced the nocturnal activity of all ring doves
      although only the highest doses were effective in old ones. A reduced amplitude
      in the activity-rest rhythm was observed in old animals in comparison to
      youngest, but it was increased after the treatments. Sleep parameters, calculated
      from the activity data, indicated a worsened sleep quality in old animals but it
      was improved with the treatments. In addition, the expression of c-fos in the SCN
      was reduced after both mentioned treatments. The results point to the SCN as a
      target for the observed nocturnal effects of L-tryptophan and melatonin, and
      support the supplemental administration of the essential amino acid L-tryptophan
      to reverse the disturbances of the circadian activity-rest cycle related with
      ageing.

PMID- 16564150
TI  - The unfolded protein response affects neuronal cell cycle protein expression:
      implications for Alzheimer's disease pathogenesis.
AB  - Alzheimer's disease (AD) is characterized by the accumulation and aggregation of
      misfolded proteins. The presence of misfolded proteins in the endoplasmic
      reticulum (ER) triggers a cellular stress response called the unfolded protein
      response (UPR). Previously, we have shown that the UPR is activated in AD
      neurons. In actively dividing cells, activation of the UPR is accompanied by
      decreased cell cycle protein expression and an arrest in the G1 phase of the cell
      cycle. Aberrant expression of cell cycle proteins has been observed in post
      mitotic neurons in AD and is suggested to be involved in neurodegeneration. In
      this study we show that the protein levels of BiP/GRP78, an ER-stress marker, is
      increased in Braak stages B and C for amyloid deposits. This is in contrast to
      the levels of cell cycle markers cyclin D1, cyclin E and phosphorylated
      retinoblastoma protein (ppRb) which are decreased in Braak stage C compared to
      Braak stage A for amyloid deposits. In addition, we report a negative correlation
      between neuronal expression of ppRb and expression levels of BiP/GRP78 in control
      and AD cases. Activation of the UPR in neuronal cells induces changes in cell
      cycle protein expression similar to these observed in AD brain. ER stress
      inducers tunicamycin and thapsigargin down-regulate cell cycle proteins ppRb and
      cyclin D1 in differentiated neuroblastoma cells. In contrast, protein levels of
      p27, a cyclin dependent kinase inhibitor, are increased after induction of ER
      stress using tunicamycin. These data suggest that activation of the UPR affects
      cell cycle protein expression in neurons during neurodegeneration in AD.

PMID- 16564151
TI  - Raman microspectroscopy as an identification tool within the phylogenetically
      homogeneous 'Bacillus subtilis' group.
AB  - Vibrational methods have multiple advantages compared to more classic,
      chemotaxonomic and even molecular microbial tools for the identification of
      bacteria. Nevertheless, their definite breakthrough in diagnostic microbiology
      laboratories is determined by their identification potential. This paper reports
      on the profound evaluation of Raman spectroscopy to identify closely related
      species by means of 68 Bacillus strains that are assigned or closely related to
      the phylogenetically homogeneous 'Bacillus subtilis'-group (sensu stricto). These
      strains were chosen to represent biological variation within the selected species
      and to create a realistic view on the possibilities of this technique The
      evaluation resulted in 49/54 correct identifications at the species level for
      intern and 15/19 for extern testing. The correct identification of strains, which
      were not represented in the training set, supports the potential as an
      identification tool within the 'B. subtilis group'. Considering the vague
      borderline between the species studied, Raman spectroscopy can be regarded here
      as a promising application for identifications at the species level.

PMID- 16564152
TI  - Vibrio navarrensis biotype pommerensis: a new biotype of V. navarrensis isolated
      in the German Baltic Sea.
AB  - The determination of phenotypic and genotypic traits of a group of closely
      related Vibrio strains from the Baltic Sea did not allow species designation. DNA
      DNA hybridization and fatty acid analysis revealed them as Vibrio navarrensis.
      Therefore we suggest these Vibrios to represent a new biotype, named V.
      navarrensis biotype pommerensis.

PMID- 16564153
TI  - Time-dependent conversion of benzyl alcohol to benzaldehyde and benzoic acid in
      aqueous solutions.
AB  - The oxidative reaction: benzyl alcohol-benzaldehyde-benzoic acid was investigated
      in time in aqueous solutions of benzyl alcohol widely used as a preservative in
      medicine and cosmetology. The solutions of benzyl alcohol were stored at
      concentrations from 0.005 to 2.09 mg/ml for a long time under different
      conditions. The presence of benzaldehyde and benzoic acid in these solutions was
      controlled by liquid chromatography on silica sorbent in water. The content of
      benzoic acid and potentially toxic benzaldehyde in solutions depending on the
      initial concentration of benzyl alcohol, on time, and on storage conditions was
      evaluated quantitatively.

PMID- 16564154
TI  - Expression of the calcium receptor in human breast cancer--a potential new marker
      predicting the risk of bone metastases.
AB  - AIMS: This study investigates whether the calcium-sensing receptor (CaR) is
      commonly expressed in primary breast cancers. The CaR controls secretion of PTHrP
      in several breast cancer cell lines and PTHrP is known to stimulate osteolysis
      during metastatic bone resorption. Whether this could explain the propensity of
      breast cancers to develop bone metastases has not been explored. METHODS: With
      Ethical Committee approval, immunohistochemistry was performed using a
      commercially available antiCaR antibody (AffinityBioReagents, Cambridge, UK) on
      archived histological sections of primary tumours from patients who died with
      advanced breast cancer. Intensity of CaR expression was assessed by two
      independent observers on a 6-point scale. RESULTS: One hundred and eight patients
      with breast cancer were found to have positive bone scans, 42 patients had died.
      Of the patients with negative bone scans, 23 had liver or lung metastases. Most
      patients with strongly expressed CaR (score 4-5 on immunohistochemistry) had bone
      metastases (13/15 patients) compared with 2/23 patients with normal bone scans (p
      < 0.001, chi(2) test). Other clinical/pathological markers (ER, PR, c-erb B-2, LN
      status) were not significantly different between patients with CaR-positive or
      CaR-negative tumours. CONCLUSIONS: CaR expression is common in a selected group
      of patients with advanced primary breast cancers. A prospective study should
      investigate if patients with CaR-positive tumours are more likely to develop bone
      metastases.

PMID- 16564155
TI  - An audit of fusion CT-PET in the management of colorectal liver metastases.
AB  - AIM: To assess the use of positron emission tomography combined with computerized
      tomography (CT-PET) with fluoro-18-2-deoxy-d-glucose ((18)F-FDG) to identify
      hyper-metabolic tumours, especially colorectal metastases (CRM). METHODS: Patient
      particulars, diagnoses and clinical outcome for each patient were studied. Twenty
      three patients underwent CT-PET, 10 males and 13 females, median age 59 (range 34
      72). Fourteen patients presented with primary liver CRM and nine had undergone
      previous liver resections. Indications for CT-PET included; suspected
      extrahepatic disease in 13/23 patients, possible hepatic recurrence 5/23 and
      clinical suspicion in 8/23 patients. RESULTS: Seven patients had a major impact
      on their management. Unexpected (not seen on CT) findings in the CRM group
      included, 7/23 (30%) patients with extrahepatic disease, 3/23 with hepatic
      metastases, 8/23 suspected of having liver or distant metastases on CT had a
      negative study. A clinical decision, based on the CT-PET report, could be
      undertaken in 21/23 patients. CONCLUSION: CT-PET is useful in patients with CRM
      where conventional imaging presents dilemmas such as: assessment of suspected
      extrahepatic disease, recurrence in liver, patients with advanced or perforated
      initial tumours.

PMID- 16564156
TI  - 15-Methoxypinusolidic acid from Biota orientalis attenuates glutamate-induced
      neurotoxicity in primary cultured rat cortical cells.
AB  - 15-Methoxypinusolidic acid (15-MPA), a pinusolide derivative isolated from Biota
      orientalis (Cupressaceae) leaves prevented glutamate-induced excitotoxicity in
      primary cultured rat cortical cells in vitro. 15-MPA had more selectivity in
      protecting neurons against N-methyl-D-aspartate (NMDA)-induced neurotoxicity than
      that induced by kainic acid (KA). The glutamate-induced increase of intracellular
      calcium ([Ca2+]i) in cortical cells was effectively reduced by 15-MPA. Moreover,
      15-MPA could successfully reduce the subsequent overproduction of nitric oxide
      (NO) and the level of cellular peroxide, and inhibit glutathione (GSH) depletion
      and lipid peroxidation induced by glutamate in our cultures. Collectively, these
      results suggested that 15-MPA attenuated glutamate-induced excitotoxicity via
      stabilization of [Ca2+]i homeostasis and suppression of oxidative stress possibly
      through the actions on the NMDA receptors.

PMID- 16564157
TI  - Characterisation of an autoreactive conformational epitope on GAD65 recognised by
      the human monoclonal antibody b78 using a combination of phage display, in vitro
      mutagenesis and molecular modelling.
AB  - Autoantibodies to the diabetes autoantigen, the 65kDa isoform of glutamic acid
      decarboxylase (GAD65), react with conformational epitopes defined according to
      linear sequences but not according to structural information, or contact sites
      with the antibody paratope. To ascertain such information for an exemplary human
      monoclonal antibody (mAb) to GAD65, b78, we combined antibody screening of phage
      displayed peptide libraries, alanine mutagenesis of selected motifs, homology
      modelling of the PLP and C-terminal regions of GAD65, and molecular dynamics to
      examine for structural effects of mutagenesis. By phage display, mAb b78 selected
      phagotopes containing acidic residues (D, E), hydrophobic residues (Y, F or W)
      and LRS that localised to a possible surface-exposed conformational epitope on
      the combined homology model. Alanine mutants of GAD65 based on deduced contact
      residues were examined for binding with b78 and control sera. Mutation of
      (524)SRL(526), (572)DF(573) and (498)KPQ(500) reduced reactivity of b78 with
      mutant GAD65 > 50%. Molecular dynamics indicated that mutation of (498)KPQ(500)
      caused structural changes that could account for effects of this mutation. Thus
      phage display in combination with molecular modelling identified contact residues
      within a highly conformational epitope for mAb b78 in the C-terminus of GAD65.
      These techniques should have broad applicability to definition of epitope
      structure.

PMID- 16564158
TI  - Stratum corneum absorption and retention of linalool and terpinen-4-ol applied as
      gel or oily solution in humans.

PMID- 16564159
TI  - Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter
      spp.
AB  - Carbapenem resistance in Acinetobacter baumannii is a growing public health
      concern and is most often mediated by OXA carbapenemases. We describe a novel
      multiplex polymerase chain reaction (PCR) assay able to detect and distinguish
      alleles encoding three subgroups of acquired OXA carbapenemases (OXA-23-like, OXA
      24-like and OXA-58-like) that are scattered in Acinetobacter spp., and a fourth
      subgroup, OXA-51-like, which appears to be intrinsic to Acinetobacter baumannii.
      Isolates belonging to two prevalent UK A. baumannii 'OXA' clones (OXA-23 clones 1
      and 2) had alleles encoding both an intrinsic OXA-51-like and an acquired OXA-23
      enzyme, whereas isolates of the 'SE clone' had only an intrinsic bla(OXA-51-like)
      allele. Genes encoding OXA-58 were detected (with bla(OXA-51-like)) in a cluster
      of related isolates from a single hospital. This simple assay will assist in
      monitoring the mechanisms responsible for carbapenem resistance in Acinetobacter
      spp.

PMID- 16564160
TI  - Parameters affecting the adhesion strength between a living cell and a colloid
      probe when measured by the atomic force microscope.
AB  - In this study, we used the colloid probe atomic force microscopy (AFM) technique
      to investigate the adhesion force between a living cell and a silica colloid
      particle in a Leibovitz's L-15 medium (L-15). The L-15 liquid maintained the
      pharmaceutical conditions necessary to keep the cells alive in the outside
      environment during the AFM experiment. The force curves in such a system showed a
      steric repulsion in the compression force curve, due to the compression of the
      cells by the colloid probe, and an adhesion force in the decompression force
      curve, due to binding events between the cell and the probe. We also investigated
      for the first time how the position on the cell surface, the strength of the
      pushing force, and the residence time of the probe at the cell surface
      individually affected the adhesion force between a living cell and a 6.84 microm
      diameter silica colloid particle in L-15. The position of measuring the force on
      the cell surface was seen not to affect the value of the maximum adhesion force.
      The loading force was also seen not to notably affect the value of the maximum
      adhesion force, if it was small enough not to pierce and damage the cell. The
      residence time of the probe at the cell surface, however, clearly affected the
      adhesion force, where a longer residence time gave a larger maximum force. From
      these results, we could conclude that the AFM force measurements should be made
      using a loading force small enough not to damage the cell and a fixed residence
      time, when comparing results of different systems.

PMID- 16564162
TI  - The first HMPC community herbal monographs.

PMID- 16564161
TI  - High presence of extended-spectrum beta-lactamases and resistance to quinolones
      in clinical isolates of Escherichia coli.
AB  - A study was conducted to detect the presence of extended-spectrum beta-lactamases
      (ESBLs) in 706 isolates of Escherichia coli, largely from outpatients (75.2%).
      The Clinical and Laboratory Standards Institute (formerly NCCLS)-recommended disk
      diffusion procedure was used to detect ESBL presence; the VITEK 2 system
      (bioMerieux, Marcy L'Etoile, France) was used to determine the susceptibility to
      antibiotics of clinical interest, and the ESBLs were characterized by biochemical
      study, determining the isoelectric point, and by molecular study with PCR. Clonal
      distribution was studied in eight hospital isolates. There were 115 ESBL
      producing isolates (16.3%), with a predominance of CTX-M9 type (58.3%). We draw
      attention to the high resistance to quinolones (>70%) in CTX-M9 and SHV enzyme
      producing isolates and the lower aminoglycoside activity in the latter.

PMID- 16564163
TI  - Value-added utilisation of recycled concrete in hot-mix asphalt.
AB  - The feasibility of partial substitution of granite aggregate in hot-mix asphalt
      (HMA) with waste concrete aggregate was investigated. Three hybrid HMA mixes
      incorporating substitutions of granite fillers/fines with 6%, 45% untreated, and
      45% heat-treated concrete were evaluated by the Marshall mix design method; the
      optimum binder contents were found to be 5.3%, 6.5% and 7.0% of grade Pen 60/70
      bitumen, respectively. All three hybrid mixes satisfied the Marshall criteria of
      the Singapore Land Transport Authority (LTA) W3B wearing course specification.
      The hybrid mix with 6% concrete fillers gave comparable resilient modulus and
      creep resistance as the conventional W3B mix, while hybrid mixes with higher
      concrete substitutions achieved better performance. X-ray diffraction (XRD)
      showed the distinct presence of free lime in the heat-treated concrete, while the
      scanning electron microscope (SEM) provided an in-depth perspective of the
      concrete grains in the HMA matrix. The results suggest feasible use of waste
      concrete as partial aggregate substitution in HMA.

PMID- 16564164
TI  - Effect of organics on selenite uptake by cementitious materials.
AB  - The behaviour of three organic ligands in suspensions of fresh and degraded
      hydrated ordinary Portland cement pastes (HCP) has been investigated. EDTA arises
      as a decontamination product whilst ISA (isosaccharinic acid) is a main
      degradation product of cellulose. GLU (gluconic acid) is used as a retarding
      organic admixture in concrete. The affinity of EDTA, ISA and GLU with HCP
      increases with the degradation state. At long contact times, ISA and GLU desorbed
      from HCP, perhaps as a result of carbonation. Their influence on the uptake of
      selenium (as SeO3(2-)) on HCP has been studied as a function of time, addition
      order and HCP degradation state. The sorption study of Se(IV) also shows a
      positive effect of the HCP degradation with R(d)=120 mLg(-1) for fresh HCP and
      1000 mLg(-1) for degraded HCP. The addition order of Se(IV) and EDTA or ISA is
      important as pre-equilibration of HCP with either EDTA or ISA drastically
      decreases the uptake of Se(IV) to 10-30 mLg(-1). Mixing of cement with GLU seems
      to reduce the strong competitive effect of other organic compounds on Se(IV)
      sorption.

PMID- 16564165
TI  - From crawling to cognition: analyzing the dynamical interactions among
      populations of neurons.
AB  - By using multi-electrode arrays or optical imaging, investigators can now record
      from many individual neurons in various parts of nervous systems simultaneously
      while an animal performs sensory, motor or cognitive tasks. Given the large
      multidimensional datasets that are now routinely generated, it is often not
      obvious how to find meaningful results within the data. The analysis of neuronal
      population recordings typically involves two steps: the extraction of relevant
      dynamics from neural data, and then use of the dynamics to classify and
      discriminate features of a stimulus or behavior. We focus on the application of
      techniques that emphasize interactions among the recorded neurons rather than
      using just the correlations between individual neurons and a perception or a
      behavior. An understanding of modern analysis techniques is crucially important
      for researchers interested in the co-varying activity among populations of
      neurons or even brain regions.

PMID- 16564167
TI  - Activating anti-CD40 antibodies induce tumour invasion by cytotoxic T-lymphocytes
      and inhibition of tumour growth in experimental liver cancer.
AB  - The aim of this study was to investigate the effects of an activating anti-CD40
      antibody (aCD40Ab) on leukocyte adhesion to tumour vessels, leukocyte migration
      and tumour growth in experimental liver cancer. Morris-Hepatoma was induced by
      subcapsular inoculation of tumour cells in the liver of ACI-rats. On day 7 and 8
      after tumour cell injection, one group of the animals received aCD40Ab. On day 13
      the tumour volume was measured and intravital microscopy was performed
      quantifying leukocyte adherence in the liver. Furthermore, immunohistological
      analyses were performed. aCD40Ab-Treated animals showed increased leukocyte
      endothelium interaction, demonstrated substantially more T- and natural killer
      (NK) cells in the tumour and had a distinctly decreased tumour volume. Our
      results show that treatment with aCD40Ab stimulates endothelial leukocyte
      adhesion in tumour vessels and migration of CD4 cells/CD8 T-cells and NK cells
      into the tumour and inhibits tumour growth. Thus, the CD40/CD154 pathway is a
      worthwhile target for adjuvant immunotherapy.

PMID- 16564166
TI  - Aberrant methylation of Fragile Histidine Triad gene is associated with poor
      prognosis in early stage esophageal squamous cell carcinoma.
AB  - The aim of this study was to understand the clinicopathological and prognostic
      significance of promoter methylation of Fragile Histidine Triad (FHIT) gene in
      esophageal cancer. FHIT methylation in 257 primary esophageal squamous cell
      carcinomas was retrospectively analyzed by methylation-specific polymerase chain
      reaction. Aberrant methylation of FHIT was found in 85 (33%) of 257 esophageal
      cancer patients. The FHIT methylation was found to be significantly associated
      with exposure to tobacco smoke (P = 0.007) and with a poor prognosis in cases of
      stage 1-2 cancer irrespective of recurrence. The hazard of failure after
      esophagectomy for stage 1-2 cancers with FHIT methylation was about 5.81 (95% CI
      = 1.15-14.07; P = 0.009) times higher than in those without. Recurrence occurred
      in 116 (45%) of the 257 patients studied. The survival after recurrence in stage
      1-2 cancers was also poorer for patients with FHIT methylation than in those
      without (HR = 2.31; 95% CI = 1.18-7.92; P = 0.03). In conclusion, aberrant
      methylation of the FHIT promoter was found to be significantly associated with
      exposure to tobacco smoke and with a poor prognosis for stage 1-2 cases, but not
      with recurrence rate. Our study suggests that FHIT promoter methylation may be an
      independent prognostic biomarker in early stage esophageal squamous cell
      carcinoma.

PMID- 16564168
TI  - Structure-activity relationship studies on UK-2A, a novel antifungal antibiotic
      from Streptomyces sp. 517-02. Part 5: Roles of the 9-membered dilactone-ring
      moiety in respiratory inhibition.
AB  - Several open-chained analogues of UK-2A, a novel antifungal antibiotic isolated
      from Streptomyces sp. 517-02, were prepared for structure-activity studies. The
      in vitro antifungal activities of these compounds against Rhodotorula
      mucilaginosa IFO 0001 and the inhibition of uncoupler-stimulated respiration in
      bovine heart submitochondrial particles (SMP) were evaluated. Oxidative
      potentials were measured by cyclic voltammetry. An analogue prepared from dihexyl
      L-glutamate showed comparable inhibitory activity as UK-2A.

PMID- 16564169
TI  - Sporadic inclusion body myositis in Japanese is associated with the MHC ancestral
      haplotype 52.1.
AB  - In Caucasians, sporadic inclusion body myositis has been associated with the MHC
      ancestral haplotypes; HLA-A1, B8, DR3 (8.1AH) and HLA-B35, DR1 (35.2AH). It is
      not known whether these haplotypes carry susceptibility for the disease in other
      ethnic groups. We report here the results of HLA-B and -DRB1 typing using a high
      resolution sequence-based technique in a cohort of 31 Japanese patients with
      definite sIBM. Patient allele frequencies were 40.3% for HLA-B*5201 (10.7% in
      controls: p<0.001) and 37.1% for HLA-DRB1*1502 (10% in controls: p<0.001). Both
      alleles were found together as part of a conserved haplotype (52.1AH) at a
      frequency of 37.1% in patients (8.4% in controls: p<0.001). This is the first
      description of a haplotypic MHC association with sporadic inclusion body myositis
      in Japanese patients. These findings indicate that different MHC ancestral
      haplotypes are associated with sIBM in different ethnic groups and further
      emphasize the importance of genetic factors in this condition.

PMID- 16564170
TI  - Review of research methods used to investigate violence in the emergency
      department.
AB  - Violence in the emergency department (ED) is of constant concern to emergency
      practitioners. Much research has been conducted on this topic but it appears that
      there has been no attempt to systematically evaluate the methods that have been
      used to investigate this problem. Therefore, the purpose of this paper is to
      review the research methods in order to identify the most effective approach for
      future use and to reveal gaps in the understanding of this problem. Most studies
      that have been conducted to investigate violence in the ED are descriptive in
      nature with the most common type retrospective or prospective surveys. Few
      interview-based studies have been conducted but these have provided an in-depth
      understanding of the perspectives and feelings of staff involved in the patient
      violence. However, none of the methods used have provided insight into the
      perspectives of patients or perpetrators of violence in the ED. To date, it
      appears that no observational or predictive studies pertaining to this problem
      have been conducted. Combining questionnaire-based and interview-based
      prospective surveys with observations could be an ideal method to investigate
      violence in the ED, as it would permit the researcher to investigate this complex
      problem more thoroughly and holistically.

PMID- 16564171
TI  - Work related post-traumatic stress as described by Jordanian emergency nurses.
AB  - BACKGROUND: Although there is a growing interest in the consequences of work
      related stress among healthcare professionals, most of the research has
      concentrated on western countries. Empirical studies of work related stress among
      health care workers from the Middle East have rarely been performed. OBJECTIVES:
      The aim of the study was to identify causes of post-traumatic stress symptoms and
      their relationship with daily work stress exposure. This qualitative study was
      undertaken using hermeneutic phenomenology and involved a representative group of
      25 nurses from Jordan. RESULTS: Work related stress symptoms were associated with
      poor social support. The findings stress the necessity for staff to support each
      other, for supervisors to support and counsel their staff and also for the
      management to promote and encourage support. Jordanian nurses are seriously at
      risk from high levels of stress symptoms. CONCLUSIONS: The results of this study
      will enable nurses to better identify and handle stressful situations in the
      early stages and in a timely fashion. It will help administrators, teachers and
      researchers to plan strategies (interventions) in the hospitals, curriculum and
      in knowledge needed to promote the quality of life for nurses.

PMID- 16564172
TI  - Type III secretion gets an LcrV tip.
AB  - Type III secretion is used by many Gram-negative pathogenic bacteria to inject
      effector proteins into eukaryotic host cells. Effector delivery requires a
      secretion apparatus, called an injectisome or needle complex, and the assembly of
      a translocation pore in a target-cell membrane. Recent work provides evidence
      that enlightens the view of how pore assembly might occur and of how the
      injectisome and the pore might be linked.

PMID- 16564173
TI  - Intraventricular epidermoids.
AB  - To study the clinical characteristics of intraventricular epidermoids, we
      analysed retrospectively 12 patients treated in our hospital and reviewed the
      literature with regard to clinical manifestations, imaging features, diagnosis,
      surgical procedures and prognosis. Four patients with lateral ventricle
      epidermoid and eight in the fourth ventricle were included in this group.
      Intraventricular epidermoids are characteristically hypodense non-enhancing
      lesions on CT scans. MRI reveals them to have long T1 and T2 relaxation times
      with slight mass effect. Total removal is ideal, but special attention should be
      paid to preservation of important neurovascular structures. Close proximity of
      tumours to cranial nerves and the brain stem pose technical difficulties in total
      removal. Cranial nerve dysfunction and aseptic meningitis are the main
      postoperative complications. Long-term prognosis for patients with
      intraventricular epidermoids and well-preserved neurological conditions is good,
      even in the case of subtotal excision. Clinical follow-up and MRI allow earlier
      diagnosis of recurrence.

PMID- 16564174
TI  - Paraneoplastic mononeuritis multiplex in non-small-cell lung carcinoma.
AB  - A 60-year-old man developed two selective peripheral mononeuropathies of the
      peroneal and later the radial nerve, shortly after a diagnosis of large-cell lung
      carcinoma. Nerve conduction studies and electromyography confirmed isolated
      lesions in both nerves, and in the case of the peroneal nerve lesion, focal
      conduction block was localised to the level of the fibula neck. Subsequent
      magnetic resonance imaging of the lower limb excluded focal compression or
      malignant infiltration along the course of the peroneal nerve, and there was no
      signal change within the nerve, prompting a diagnosis of paraneoplastic
      mononeuritis multiplex. Anti-neuronal antibodies and serological markers of
      systemic vasculitis were negative. Neither the patient's large-cell lung
      carcinoma nor mononeuritis multiplex responded to chemotherapy, and he died
      within 6 months of the initial diagnosis.

PMID- 16564175
TI  - Synthesis of ethylenediamine linked beta-cyclodextrin dimer and its analytical
      application for tranilast determination by spectrofluorimetry.
AB  - A synthesis of beta-cyclodextrin (beta-CD) dimer, containing two beta-CD moieties
      that are linked through their sides by ethylenediamine, was presented. The dimer
      was characterized by means of IR, (1)H NMR, (13)C NMR, and elemental analysis.
      The inclusion complexation behavior of beta-cyclodextrin dimer with tranilast was
      studied in an aqueous KH(2)PO(4)-citric acid buffer solution of pH 2.00 at room
      temperature by spectrofluorimetry. Based on the significant enhancement of
      fluorescence intensity of tranilast, a spectrofluorimetric method with high
      sensitivity and selectivity was developed for the determination of tranilast in
      bulk aqueous solution in the presence of ethylenediamine beta-CD dimer. The
      apparent association constant of the complex was 8.39 x 10(3) L mol(-1), and the
      linear range was 10.8-1.40 x 10(4) ng mL(-1) with the detection limit 3.2 ng mL(
      1). There was no interference from the excipients normally used in tablets and
      serum constituents. The proposed method was successfully applied to the
      determination of tranilast in serum.

PMID- 16564176
TI  - Dielectric and optical properties of nanometric nickel silicides from valence
      electrons energy-loss spectroscopy experiments.
AB  - Valence and Core Electron Energy Loss Spectroscopy (VEELS and CEELS) experiments
      are performed from nanocrystallized nickel silicide thin films. Three different
      silicide compounds are identified in the films. Their chemical compositions are
      determined from Ni-L(2,3) to Si-K core edges quantification. The results obtained
      are coherent within less than 2% error with the pure Ni2Si, NiSi and NiSi2
      phases. The analysis of the shape and energy position of Ni-L(2,3) near edge
      structures and volume plasmon peaks indicates that both are reliable signatures
      to identify unambiguously each compound. Nickel silicides low-loss spectra have
      been submitted as references to the EELS database (www.cemes.fr~eelsdb). Low-loss
      spectra are processed to extract single scattering spectra and determine the
      dielectric function. The results show that nickel silicides dielectric functions
      deduced from VEELS are in quite good agreement with epsilon1 and epsilon2 deduced
      from ellipsometry experiments. The optical properties (refractive index (n),
      absorption coefficient (k), reflectivity (R%) and resistivity (rho(opt))),
      calculated from VEELS dielectric function are then compared in details with the
      data resulting from others techniques available in the literature. We show that,
      except some minor divergences, the nickel silicides optical properties are
      generally well reproduced. This indicates that VEELS is a relevant technique for
      accessing reliably to physical properties and can be a successful alternative to
      conventional techniques when high spatial resolution is needed.

PMID- 16564177
TI  - The structure of a ketoreductase determines the organization of the beta-carbon
      processing enzymes of modular polyketide synthases.
AB  - The structure of the ketoreductase (KR) from the first module of the erythromycin
      synthase with NADPH bound was solved to 1.79 A resolution. The 51 kDa domain has
      two subdomains, each similar to a short-chain dehydrogenase/reductase (SDR)
      monomer. One subdomain has a truncated Rossmann fold and serves a purely
      structural role stabilizing the other subdomain, which catalyzes the reduction of
      the beta-carbonyl of a polyketide and possibly the epimerization of an alpha
      substituent. The structure enabled us to define the domain boundaries of KR, the
      dehydratase (DH), and the enoylreductase (ER). It also constrains the three
      dimensional organization of these domains within a module, revealing that KR does
      not make dimeric contacts across the 2-fold axis of the module. The quaternary
      structure elucidates how substrates are shuttled between the active sites of
      polyketide synthases (PKSs), as well as related fatty acid synthases (FASs), and
      suggests how domains can be swapped to make hybrid synthases that produce novel
      polyketides.

PMID- 16564178
TI  - Comparison of strontium-89 solution sources in UK hospitals, 2003.
AB  - Concerns have been raised within the nuclear medicine field about the accuracy of
      measurements of 89Sr. The 85Sr impurity present in the 89Sr solution has a
      significant effect on the response of radionuclide calibrators used in hospitals.
      A comparison was conducted between the National Physical Laboratory (NPL) and the
      UK hospital physics community. Only 58% of the results were within 5% of the NPL
      value. Work at NPL has resulted in correction factors for the NPL secondary
      standard radionuclide calibrator and for Capintec calibrators, which will produce
      a significant improvement in performance.

PMID- 16564179
TI  - The sequence of regional ventricular motion.
AB  - OBJECTIVE: The chronology of electrical events that mechanically activate the
      myocardium has been described as initiating at the level of the septum, spreading
      to the apex, then to the bodies of both ventricles and eventually to the base of
      the heart (apex-to base activation). It has recently been suggested that the
      myocardium is a single muscular band that conforms a double-loop helicoid.
      Contraction of the myocardium would follow the trajectory of the muscular fibers
      that originate at the pulmonary artery towards the body of the left ventricle and
      to the aorta (base-to apex contraction). This would explain the movements of the
      base of the heart and the twisting motion of the ventricles seen at magnetic
      resonance studies. METHODS: Temporal Fourier analysis of equilibrium
      radionucleide angiocardiography, by studying the topography of the regional
      myocardial mechanical displacement corresponding to the wave front of electro
      mechanical activation, provides information on the sequence of regional
      ventricular contraction was used in 29 normal individuals to observe the sequence
      of myocardial motion. RESULTS: Analysis disclosed that the base of the heart
      first moves (right then left ventricle) and mechanical movement later descends to
      involve the apex and the septum. These findings are in concordance with the
      proposed activation of the helical myocardium and open the way to more complex
      studies. CONCLUSIONS: Although electrical activation of the myocardium (QRS
      complex) follows a septum-apex-body-base of the left ventricle sequence,
      mechanical activation follows a base-to-apex sequence. This is likely to be
      related to anisotropic propagation of the electromechanical stimulus throughout
      the myocardial band once the electrical stimulus has been delivered at the base
      of the heart.

PMID- 16564180
TI  - Use of cardiac magnetic resonance imaging in surgical ventricular restoration.
AB  - OBJECTIVE: Surgical ventricular restoration (SVR) is a promising modality for
      treatment of heart failure due to left ventricular systolic dysfunction,
      particularly that due to ischemic heart disease. The role of MRI in improving
      diagnosis, operative planning, and follow-up is reviewed to analyze how one
      examination may define a spectrum of important considerations. METHODS: Proper
      patient selection and optimal surgical planning relies on accurate assessment of
      measures of ventricular volume, function, and viability, and of the mechanics of
      the mitral valve apparatus. A complete preoperative imaging evaluation includes
      assessment of the left ventricular volume (both systolic and diastolic), regional
      and global systolic function, viability of the target area for surgical exclusion
      and of the remote myocardium, determination of the adequacy of the remote
      myocardium remaining after proposed SVR to support circulatory function, and of
      the mitral annular dilatation and inter papillary muscle spacing, factors which
      contribute to functional mitral regurgitation. RESULTS: Cardiac magnetic
      resonance imaging (MRI) allows a complete evaluation of these quantities: the
      ventricular systolic and diastolic volumes (and hence ejection fraction) are
      easily assessed reproducibly and accurately; the regional wall motion of the
      asynergic area and the remote myocardium can be measured by several quantitative
      means, including with myocardial tagging, and the presence or absence of
      nonviable, irreversible scar can be detected with gadolinium-based interstitial
      contrast agents. Furthermore, an accurate measurement of the mitral annular
      dimensions and the papillary muscle spacing can be easily performed using cardiac
      MRI, allowing planning of effective therapy for mitral regurgitation.
      CONCLUSIONS: The entire imaging study can be performed in less than 1h, making
      cardiac MRI a truly useful and comprehensive tool in planning SVR, and for
      subsequently evaluating results.

PMID- 16564181
TI  - Cell biology, MRI and geometry: insight into a microscopic/macroscopic marriage.
AB  - OBJECTIVE: The concept of cell therapy as an adjunctive therapy to myocardial
      surgical revascularization for patients with severe coronary artery disease is
      illustrated by two case reports of ischemic cardiac disease that were unsuitable
      for revascularization by coronary grafting. The potential interaction of cell
      therapy, magnetic resonance imaging (MRI) of viability, and left ventricle (LV)
      restoration is described. METHODS: Each patient had an ejection fraction below
      30%, a relatively conical heart, and MRI gadolinium scan showing predominantly
      viable muscle. RESULTS: Intramyocardial injections of autologous bone marrow
      derived cells (BMC) were performed along with either incomplete coronary artery
      bypass grafting (CABG) (to mother regions) or with transmyocardial laser
      revascularization (TMLR). An improvement in contractile function was seen at 6-12
      month intervals after the procedure. CONCLUSIONS: The implications of possible
      underlying mechanisms of improvement in both myocardial perfusion and
      contractility suggest the striking importance of both micro- and macroenvironment
      for any cell-based therapeutic strategy. These observations imply that the
      interaction of cell biology, viability by MRI and geometry may be important in
      the future, as geometry can be restored surgically, and the new architectural
      form may develop enhanced function if it contains viable tissue and cell-based
      treatment can be delivered.

PMID- 16564182
TI  - Visualization of tissue velocity data from cardiac wall motion measurements with
      myocardial fiber tracking: principles and implications for cardiac fiber
      structures.
AB  - OBJECTIVE: The spatial arrangement of myocardial fiber structure affects the
      mechanical and electrical properties of the heart. Therefore, information on the
      structure and dynamics of the orientation of the muscle fibers in the human heart
      might provide significant insight into principles of the mechanics of normal
      ventricular contraction and electrical propagation and may subsequently aid pre-
      and postsurgical evaluation of patients. Fiber orientation is inherently linked
      to cardiac wall motion, which can be measured with phase contrast magnetic
      resonance imaging (MRI), also termed tissue phase mapping (TPM). METHODS: This
      study provides initial results of the visualization of velocity data with fiber
      tracking algorithms and discusses implications for the fiber orientations. In
      order to generate datasets with sufficient volume coverage and resolution TPM
      measurements with three-dimensional (3D) velocity encoding were executed during
      breath-hold periods and free breathing. Subsequent postprocessing evaluation with
      a tracking algorithm for acceleration fields derived from the velocity data was
      performed. RESULTS: Myocardial acceleration tracking illustrated the dynamics of
      fiber structure during four different phases of left ventricular performance,
      that include isovolumetric contraction (IVC), mid-systole, isovolumetric
      relaxation (IVR), and mid-diastole. Exact reconstruction of the myocardial fiber
      structure from velocity data requires mathematical modeling of spatiotemporal
      evolution of the velocity fields. CONCLUSIONS: 'Acceleration fibers' were
      reconstructed at these four phases during the cardiac cycle, and these findings
      may become (a) surrogate parameters in the normal ventricle, (b) baseline markers
      for subsequent clinical studies of abnormal hearts with altered architecture, and
      (c) may help to explain and illustrate functional features of cardiac performance
      in structural models like the helical ventricular myocardial band.

PMID- 16564183
TI  - New concepts of cardiac anatomy and physiology. Rethinking the cardiac helix: a
      structure/function journey. Proceedings of the Liverpool Symposium. May 28, 2005.
      Liverpool, United Kingdom.

PMID- 16564184
TI  - Septal structure and function relationships parallel the left ventricular free
      wall ascending and descending segments of the helical heart.
AB  - OBJECTIVE: Determine if ventricular septum structure and function relationships
      parallel the left ventricular free wall descending and ascending segments of the
      helical heart. METHODS: Forty pigs (30-38 kg) were studied physiologically by
      sonomicrometer to determine if septal fiber orientation resembled responses in
      the free wall. Following pilot studies in the non-bypassed heart, a right
      ventriculotomy was made to place septum crystals with fiber orientations that
      were either perpendicular to or reflected simultaneous free wall measurements.
      Postbypass measurements tested responses to positive (dopamine) and negative
      (esmolol) inotropic agents. RESULTS: Similar oblique fiber directions were found
      for baseline percent systolic shortening (SS%) in the free wall and septum; free
      wall descending and ascending SS% were 21+/-3% and 10+/-3%, and 13+/-2% and 12+/
      2%, respectively, in the septum. Conversely, impaired shortening occurred when
      transverse fiber direction was tested. Both oblique areas demonstrated comparable
      time-delay changes between free wall and septal descending and ascending segment
      at onset (75+/-11 ms) and termination (86+/-21 ms) of contraction. Dopamine
      increased heart rate and caused a similar increase of free wall descending and
      ascending segment SS% to 24+/-2% and 14+/-3% (p<0.05), and septal SS% response to
      16+/-2% and 15+/-2% (p<0.05), and comparable decrease of time-delay changes of
      shortening between ascending and descending segments of 54+/-6 ms and 68+/-10 ms,
      respectively (p<0.05). Conversely, esmolol decreased heart rate and similarly
      reduced SS% in left ventricular free wall (descending: 18+/-4%; ascending: 7+/
      4%; p<0.05) and septum (descending: 10+/-2%; ascending: 10+/-3%; p<0.05). Time
      delay of contraction between segments was increased to 91+/-4 ms (p<0.05), but
      the hiatus at the end of shortening remained unchanged, due to prolonged
      endocardial contraction. CONCLUSIONS: Septal structure and function relationships
      parallel the left ventricular free wall ascending and descending segments,
      thereby supporting the helical heart fiber spatial relationships. The oblique
      fiber orientation may make the septum become the 'lion of right ventricular
      function'.

PMID- 16564185
TI  - Spatiotemporal dynamics and connectivity pattern differences between centrally
      and peripherally presented faces.
AB  - Most neuroimaging studies on face processing used centrally presented images with
      a relatively large visual field. Images presented in this way activate widespread
      striate and extrastriate areas and make it difficult to study spatiotemporal
      dynamics and connectivity pattern differences from various parts of the visual
      field. Here we studied magnetoencephalographic responses in humans to centrally
      and peripherally presented faces for testing the hypothesis that processing of
      visual stimuli with facial expressions of emotions depends on where the stimuli
      are presented in the visual field. Using our tomographic and statistical
      parametric mapping analyses, we identified occipitotemporal areas activated by
      face stimuli more than by control conditions. V1/V2 activity was significantly
      stronger for lower than central and upper visual field presentation. Fusiform
      activity, however, was significantly stronger for central than for peripheral
      presentation. Both the V1/V2 and fusiform areas activated earlier for peripheral
      than for central presentation. Fast responses in the fusiform were found at 70-80
      ms after image onset, as well as a response at 130-160 ms. For peripheral
      presentation, contralateral V1/V2 and fusiform activated earlier (10 ms and 23
      ms, respectively) and significantly stronger than their ipsilateral counterparts.
      Mutual information analysis further showed linked activity from bilateral V1/V2
      to fusiform for central presentation and from contralateral V1/V2 to fusiform for
      lower visual field presentation. In the upper visual field, the linkage was from
      fusiform to V1/V2. Our results showed that face stimuli are processed
      predominantly in the hemisphere contralateral to the stimulation and demonstrated
      for the first time early fusiform activation leading V1/V2 activation for upper
      visual field stimulation.

PMID- 16564187
TI  - Thoracoscopic sympathectomy for Raynaud's phenomenon--a long term follow-up
      study.
AB  - OBJECTIVES: To assess the long term results of thoracoscopic sympathectomy for
      Raynaud's phenomenon. DESIGN, MATERIALS AND METHODS: A retrospective study of 34
      consecutive patients who were treated for Raynaud's phenomenon by thoracoscopic
      sympathectomy from 1996 to 2005. Eight patients presented with ulcerations of the
      digits and 10 had severe ischaemia without ulcerations. The hospital records were
      retrieved and questionnaires were mailed to the patients for follow-up. RESULTS:
      The questionnaire was answered by 91% of patients after a median follow-up time
      of 40 months. An immediate effect was seen in 83% of the patients but symptoms
      recurred in 60% during the follow-up period. Compensatory sweating occurred in 63
      and 30% reported gustatory sweating. Thirteen patients (43%) regretted having the
      operation. CONCLUSION: The majority of patients with Raynaud's phenomenon have an
      excellent immediate effect from thoracoscopic sympathectomy and one third achieve
      a long lasting effect. Side effects are frequent. We now only use thoracoscopic
      sympathectomy in severe cases of Raynaud's phenomenon.

PMID- 16564186
TI  - Use of arterially perfused rabbit ventricular wedge in predicting arrhythmogenic
      potentials of drugs.
AB  - INTRODUCTION: A growing number of drugs have reportedly been associated with
      delayed ventricular repolarization and a potentially fatal but rare arrhythmia,
      torsade de pointes (TdP). There is obviously a call for a validated proarrhythmia
      model that distinguishes proarrhythmic drugs from nonarrhythmogenic drugs.
      METHODS: In this article, we validated the arterially perfused rabbit left
      ventricular wedge preparation model and examined its use in predicting
      proarrhythmic potentials of drugs. A fairly detailed methodological description
      about this technically challenging model was given, aiming to help others
      establish the assay successfully. Parameters commonly used in the action
      potential studies were verified and critical experimental conditions (e.g.
      stability and reproducibility of recordings) were examined. Six commercially
      available compounds with various proarrhythmic potentials were administered in
      the model to evaluate their correlations with individual clinical outcomes.
      RESULTS: Our study indicated that, in a successful experiment, the action
      potential duration (APD) can be stably maintained for several hours without
      intervention. Dofetilide, DL-sotalol, cisapride, risperidone and moxifloxacin
      increased endo- and epicardial APD(90), QT interval and T(P-E) (peak-to-end time
      of the T wave) in a reverse use-dependent manner within clinically relevant
      concentration ranges. Phase 2 early afterdepolarizations (EADs) were observed at
      1.6, 2.3, 16.7, 37.5 and 7.9 fold, respectively, their corresponding unbound
      therapeutic concentrations. In contrast, fluoxetine at up to 3 microM
      (approximately 35 fold unbound therapeutic mean plasma concentration after 60
      mg/day, p.o. for 5 weeks) had only a mild prolonging effect on APD(90) and QT
      with essentially no effect on T(P-E). DISCUSSION: Our results strongly support
      the usefulness of this model in predicting a compound's arrhythmogenic potential
      in humans within clinically relevant concentration ranges, and the experimental
      results with this model need to be interpreted in light of each drug's
      pharmacokinetic and pharmacodynamic behavior in clinic.

PMID- 16564188
TI  - Strut failure in the body of the zenith abdominal endoprosthesis.
AB  - OBJECTIVES: Endovascular repair of abdominal aortic aneurysm is a technology that
      has undergone rapid technological evolution with a number of different types of
      grafts developed and concern has been the structural integrity of the metallic
      endoskeleton. We describe our experiences of strut failure in the Zenith
      abdominal aneurysm endograft device. DESIGN/MATERIALS/METHODS: Eighty-four
      patients have undergone endovascular repair of their abdominal aortic aneurysm at
      Christchurch Hospital from 1996 to 2005, all with the Zenith endoprosthesis. All
      available plain radiographs of the endoprosthesis (AP and lateral planes) were
      reviewed retrospectively, by a single experience observer, to assess strut
      failure. RESULTS: Three cases of strut failure in second-generation grafts were
      identified, each in the inferior body of the graft above the iliac bifurcation.
      There was no clear evidence that these strut failures were associated with
      clinical complications. CONCLUSION: This is the first time that strut failure in
      the Zenith abdominal endoprosthesis has been reported. Whilst in each of our
      three cases this does not appear to have been of clinical significance, these
      findings re-iterate the necessity of life-long surveillance of this technology.

PMID- 16564189
TI  - Sleep loss, learning capacity and academic performance.
AB  - At a time when several studies have highlighted the relationship between sleep,
      learning and memory processes, an in-depth analysis of the effects of sleep
      deprivation on student learning ability and academic performance would appear to
      be essential. Most studies have been naturalistic correlative investigations,
      where sleep schedules were correlated with school and academic achievement.
      Nonetheless, some authors were able to actively manipulate sleep in order to
      observe neurocognitive and behavioral consequences, such as learning, memory
      capacity and school performance. The findings strongly suggest that: (a) students
      of different education levels (from school to university) are chronically sleep
      deprived or suffer from poor sleep quality and consequent daytime sleepiness; (b)
      sleep quality and quantity are closely related to student learning capacity and
      academic performance; (c) sleep loss is frequently associated with poor
      declarative and procedural learning in students; (d) studies in which sleep was
      actively restricted or optimized showed, respectively, a worsening and an
      improvement in neurocognitive and academic performance. These results may been
      related to the specific involvement of the prefrontal cortex (PFC) in
      vulnerability to sleep loss. Most methodological limitations are discussed and
      some future research goals are suggested.

PMID- 16564190
TI  - Monocarboxylate transporters and their role in glucose homeostasis in ruminants.

PMID- 16564191
TI  - Characterization of microporous aluminophosphate IST-1 using (1)H Lee-Goldburg
      techniques.
AB  - The presence of two independent methylamine species in microporous
      aluminophosphate IST-1 (|(CH(3)NH(2))(4)(CH(3)NH(+)(3))(4)(OH(
      ))(4)|[Al(12)P(12)O(48)]) has been shown previously by synchrotron powder X-ray
      diffraction. One of these species, [N(1)-C(1)], links to a six-coordinated
      framework Al-atom [Al(1)], while the other methylamine [N(2)-C(2)] is protonated
      and hydrogen-bonded to three O-atoms [O(1), O(2) and O(12)]. We revisit the
      structure of IST-1 and report the complete assignment of the (1)H NMR spectra by
      combining X-ray data and high-resolution heteronuclear/homonuclear solid-state
      NMR techniques based on frequency-switched Lee-Goldburg homonuclear decoupling
      and (31)P-(31)P homonuclear recoupling. Careful analysis of the 2D (1)H-X
      homonuclear correlation (X=(1)H) and 2D heteronuclear correlation (X=(13)C, (31)P
      and (27)Al) spectra allowed the distinction of both methylamine species and the
      assignment of all (31)P and (13)C resonances. For the first time at a relatively
      high (9.4 T) magnetic field, symmetric doublet patterns have been observed in the
      (13)C spectra, caused by the influence of the (14)N second-order quadrupolar
      interaction.

PMID- 16564192
TI  - The effect of treatment with moxifloxacin or azithromycin on acute bacterial
      rhinosinusitis in mice.
AB  - OBJECTIVE: Acute bacterial rhinosinusitis, which is a major health problem, is
      treated with antibiotics. We developed a mouse model of acute bacterial
      rhinosinusitis to gain a better understanding of the pathophysiology of the
      disease. Our goal was to investigate the response to acute rhinosinusitis when
      treated with either a bactericidal or a bacteriostatic antibiotic. METHODS:
      C57BL/6 mice were infected intranasally with Streptococcus pneumoniae. One day
      after inoculation, the mice were treated with either moxifloxacin (bactericidal)
      or azithromycin (bacteriostatic). Different groups were euthanized during the
      first five days post-inoculation. Bacterial counts from nasal lavage culture and
      the cell markers GR1, CD11b, CD3, CD4, and CD8 in sinus tissue were evaluated by
      flow cytometry. RESULTS: Azithromycin led to rapid clearance of the bacteria and
      of the inflammation in contrast to placebo. Surprisingly, moxifloxacin showed a
      limited effect. Investigations of this limited effect of moxifloxacin suggested a
      high metabolic clearance, a low concentration at the site of infection, and low
      persistent post-antibiotic effects of moxifloxacin in mice. CONCLUSION: Our
      animal model of acute sinusitis has great utility for studying the disease, but
      the difference between mice and man must always be considered in making
      extrapolations from animal experiments to the human experience.

PMID- 16564193
TI  - Rh proteins vs Amt proteins: an organismal and phylogenetic perspective on CO2
      and NH3 gas channels.
AB  - Rh (Rhesus) proteins are homologues of ammonium transport (Amt) proteins.
      Physiological and structural evidence shows that Amt proteins are gas channels
      for NH(3), but the substrate of Rh proteins, be it CO2 as shown in green alga, or
      NH3/NH4+ as shown in mammalian cells, remains disputed. We assembled a large
      dataset generated of Rh and Amt to explore how Rh originated from and evolved
      independently of Amt relatives. Analysis of this rich data implies that Rh was
      split from Amt first to emerge in archaeal species. The Rh ancestor underwent
      divergence and duplication along speciation, leading to neofunctionalization and
      subfunctionalization of the Rh family. The characteristic organismal distribution
      of Rh vs. Amt reflects their early separation and subsequent independent
      evolution: they coexist in microbes and invertebrates but do not in fungi,
      vascular plants or vertebrates. Rh gene-duplication was prominent in vertebrates:
      while epithelial RhBG/RhCG displayed strong purifying selection, erythroid Rh30
      and RhAG experienced different episodes of positive selection in each of which
      adaptive evolution occurred at certain time points and in a few codon sites.
      Mammalian Rh30 and RhAG were subject to particularly strong positive selection in
      some codon sites in the lineage from rodents to human. The grounds of this
      adaptive evolution may be driven by the necessity to increase the surface/volume
      ratio of biconcave erythrocytes for facilitative gas diffusion. Altogether, these
      results are consistent with Rh proteins not being the orthologue of Amt proteins
      but having gained the function for CO2/HCO3- transport, with important roles in
      systemic pH regulation.

PMID- 16564194
TI  - Structural and functional insights into the AmtB/Mep/Rh protein family.
AB  - X-ray crystallography revealed a similar architecture of the ammonium transport
      protein AmtB from Escherichia coli and the homologous protein Amt-1 from
      Archaeoglobus fulgidus. Furthermore, the atomic structures suggest that the
      proteins conduct ammonia (NH3) rather than ammonium ions (NH4+). These findings
      indicate that the more than 350 members of the ammonium transporter/methylamine
      permease/Rhesus (Amt/Mep/Rh) protein family found in archaea, bacteria, fungi,
      plants and animals are ammonia-conducting channels rather than ammonium ion
      transporters. The essential part of these proteins is the narrow hydrophobic
      ammonia-conducting pore with two highly conserved histidine residues located in
      the middle of the pore. A specific ammonium ion binding site is found at the
      extracellular entry site of E. coli AmtB. E. coli AmtB and its regulator GlnK
      form an effective ammonium sensory system that couples intracellular gene
      regulation by the nitrogen control system to external changes in ammonium
      availability. Based on structural and functional analysis of various mutants, two
      conserved histidine residues were found to be essential for substrate conductance
      also in the functional eukaryotic ammonium transporters. The next big challenge
      in the field surely is to determine the atomic structure of Rh proteins.

PMID- 16564195
TI  - Spondylarthropathy striking prevalence in a 19th-20th century Portuguese
      collection.
AB  - The concept of spondylarthropathy (SPAP) covers a series of pathologies sharing a
      common genetic basis and infectious triggers. OBJECTIVES: To present and discuss
      the prevalence of SPAP in the Coimbra identified skeletal collection, a 19th-20th
      century Portuguese sample. MATERIALS AND METHODS: Each of the 505 individuals was
      macroscopically examined; each joint being assessed for degenerative,
      inflammatory, ankylosing, entesopathic, traumatic, congenital, infectious, or
      associated lesions. For the diagnosis of SPAP, besides the criteria proposed by
      Rogers and Rothschild, it was also applied a new set of criteria established by
      Martin-Dupont. Associated and differential diagnoses were also discussed.
      RESULTS: Using these latter criteria, SPAP was definitely diagnosed in 34
      individuals (6.7%), mostly women and elderly individuals. Furthermore, SPAP was
      diagnosed as probable in 32 (6.3%) and could not be excluded in 98 skeletons
      (19.4%). Except for the third category, the results were close to those obtained
      when using the arguments of others authors. DISCUSSION: The specificity of each
      criterion is discussed, and the results are precautiously compared with other
      studies both from past and contemporary samples. Graduating the diagnosis as
      certain, probable or unexcluded, seems to us of interest, leading to etiological
      discussion as in clinical practice. CONCLUSION: The high prevalence of SPAP
      achieved for the Portuguese collection might be explained by high exposure to
      infectious triggers.

PMID- 16564196
TI  - Adolescent complainants of sexual assault; injury patterns in virgin and non
      virgin groups.
AB  - INTRODUCTION: Misconceptions about the likelihood of sustaining injuries
      following rape or sexual assault can have a detrimental effect on the justice
      process. This is particularly noticeable with regard to first time intercourse.
      Forensic physicians have a duty to put any examination findings in context. This
      study sets out to compare the findings in virgin and non-virgin adolescents seen
      at the St Mary's Sexual Assault Referral Centre, after an allegation of non
      consensual intercourse. METHODOLOGY: The records of all females aged 12-17 years
      old, examined in an 18 month period were reviewed. RESULTS: Two hundred and
      twenty-four clients fitted this group with a mean age of 14.8 years. Eighty-one
      were "virgins" and 97 had been sexually active prior to the assault. The virgin
      group took longer to present for examination then the non-virgin group (90 h
      compared to 44 h). Of all clients 51% had a non-genital injury. These tended to
      be minor. 32% of the non-virgin group had a genital injury. In the virgin group,
      53% had a genital injury, however only 32% had the type of genital injury that
      would leave permanent evidence of penetration (i.e. if examined several weeks or
      more later). Alcohol use prior to assault was common. CONCLUSIONS: Genital and or
      body injuries are not routinely found in adolescents after an allegation of rape
      or sexual assault even when there has not been previous sexual experience. The
      absence of injury does not exclude the possibility of intercourse, whether with
      or without consent.

PMID- 16564197
TI  - Socio-cultural aspect of sexual practices and sexual offences - an Indian
      scenario.
AB  - Ignorance of the law of the land is no defence. Furthermore, it is a legal dictum
      that one should not be held criminally liable unless possessing a guilty mind.
      But during trials of some sexual offences in India it is often observed that the
      accused did not know that he had committed an offence because the crime in
      question was a part of his socio-cultural milieu. India is a vast country with
      great socio-cultural diversity and many different ethnic groups, each with its
      own distinct cultures. However, the entire Indian culture is religion based and
      finds its root from the ancient Holy Scriptures. The sexual culture of Indian
      society stems from the Kama Sutra of Vatsyayana, an epic on sex. This text is
      considered holy and is accepted culturally, even though many practices contained
      therein are offences under modern law. Child marriages and arranged marriages are
      an integral part of Indian society and in some tribes, even prostitution is
      socially sanctioned. However, all of these are also against the law. Many of the
      conflicts observed between the sexual practices that are accepted in Indian
      culture but not by the law can be explained on the basis that the Indian legal
      system is borrowed from that of the British.

PMID- 16564198
TI  - Review of 212 individuals attending a city centre genitourinary medicine clinic
      following acute sexual assault.
AB  - A retrospective case note review of 212 individuals (190 women) attending a city
      centre Genitourinary Medicine clinic between 1/4/2002 and 31/3/2004 following an
      acute sexual assault. Direct referral by the Forensic Medical Examiner to the
      dedicated weekly clinic for victims of sexual assault facilitated the attendance
      of 55/113 attending the dedicated clinic. The 99 individuals who did not disclose
      a recent assault as the reason for attendance were seen at routine clinics. One
      third of individuals attending the dedicated clinic were less than 16 years old,
      reflecting the facilitated referral pathway. Those attending the dedicated clinic
      were more likely to be offered the extended service outlined in the departmental
      protocol. Twenty four sexually transmitted infections were detected in 23 (11%)
      individuals but 23/24 could have been acquired during other recent consensual
      sexual activity. Overall, the assailant was known to the victim in 53% cases,
      there was an allegation of violence associated with the assault in 20%, suspicion
      of a drug facilitated ('spiked drink') assault in 24% and admission of alcohol
      intoxication in 11% cases. The 22/212 (10%) who were male were more likely to
      present to a routine clinic.

PMID- 16564199
TI  - Somnambulistic sexual behaviour (sexsomnia).
AB  - Somnambulism or sleepwalking is a viable defence on the basis of automatism. The
      behaviours that occur during sleepwalking can be highly complex and include
      sexual behaviour of all types. Somnambulistic sexual behaviour (also called
      sexsomnia, sleep sex) is considered a variant of sleepwalking disorder as the
      overwhelming majority of people with Sexsomnia have a history of parasomnia and a
      family history of sleepwalking. Sexual behaviour during a sleep automatism can
      vary from explicit sexual vocalisations, to violent masturbation, to complex
      sexual acts including anal, oral and vaginal penetration. A recent case in
      England is reported where the defendant was acquitted on 3 charges of rape on the
      basis of automatism due to somnambulistic sexual behaviour.

PMID- 16564200
TI  - Medico-legal approach to sexual assault victims: the Belgian situation.
AB  - Clinical forensic medicine is a relatively new discipline in Belgium although
      (sexual) violence has been around for centuries. A brief overview of the Belgian
      legal system and the way it interacts with forensic medicine is presented, with
      special emphasis on the investigation of complainants of sexual violence. The
      epidemiology of sexual violence in Belgium is discussed together with the
      procedures that were developed by the government to standardise the medical
      examination of sexual assault victims.

PMID- 16564201
TI  - Facilities for complainants of sexual assault throughout the United Kingdom.
AB  - BACKGROUND: A sexual assault referral centre (SARC) is a model of service
      established to address the forensic and therapeutic needs arising following
      sexual assault. As yet, only a minority of urban areas in England are served by
      one, the rest of the United Kingdom (UK) being served by police victim
      examination suites. OBJECTIVE: To examine variations in service offered to
      complainants of sexual assault within the United Kingdom in 2005. METHODS: A
      purpose designed questionnaire sent to all areas of the United Kingdom. Data were
      received and analysed from 12 of 13 SARCs and 54 of 58 non SARC services.
      RESULTS: Very wide disparities in service, most marked between SARC and non SARC
      services. SARCs see a proportion of complainants from non-police sources. The non
      SARC services do not usually offer a forensic examination without police
      involvement, and a significant minority have so few doctors that they cannot
      provide a 24h rota for examinations. Inadequate numbers of forensic physicians
      are available for child examinations, and a robust service for 'acute child
      sexual assault' is virtually absent. Photodocumentation with appropriate safe
      storage is available in all SARCs, while 45% of non SARCs have no facility for
      photodocumentation. DNA contamination issues were perceived to be significant in
      many of non SARC services. Most non SARC services for adults do not provide
      baseline screening for sexually transmitted infection (STI) or offer prophylaxis
      against STIs. Follow up is by referral to local clinics which complainants may
      have to arrange themselves. Funded counselling is rare in the non SARCs with the
      exception of Yorkshire. CONCLUSION: In the non SARC services, lack of co
      operative working with local health services, lack of equipment, and lack of 'in
      house' medical follow up arrangements is the norm. Many areas rely on the good
      will of a small number of doctors to provide a service without a rota.

PMID- 16564202
TI  - Receptors for auxin: will it all end in TIRs?
AB  - The role of TIR1 in ubiquitination and regulated degradation of Aux/IAA
      transcription factors has been recognized for some years, but recent results have
      shown that TIR1 itself is also the binding site for auxin. The affinity and
      specificity of TIR1 match properties anticipated of a nuclear auxin receptor and
      we look at how they compare with the properties of ABP1. We also consider the
      mechanism of auxin action via TIR1 and the likelihood that the TIR1 family could
      account for all auxin responses. It seems likely that the TIR1 system can account
      for a large part of the repertoire of auxin-mediated responses, but maybe not
      all.

PMID- 16564203
TI  - P3a from auditory white noise stimuli.
AB  - OBJECTIVE: P3a and P3b event-related brain potentials (ERPs) were elicited with
      an auditory 3-stimulus (target, distracter, standard) paradigm in which subjects
      responded only to the target. METHODS: Distracter stimuli consisted of white
      noise, novel sounds, or a high frequency tone, with stimulus characteristics
      perceptually controlled. Task difficulty was varied as easy and hard by changing
      the pitch difference between the target and standard stimuli. RESULTS: Error rate
      was greater and response time longer for the hard task. P3a distracter amplitude
      was largest for the white noise and novel stimuli, with maximum amplitude over
      the central recording sites, and larger for the hard discrimination task. P3b
      target amplitude was unaffected by distracter type, maximum over the parietal
      recording sites, and smaller and later for the hard task. CONCLUSIONS: The
      findings indicate that white noise stimuli can produce reliable P3a components.
      SIGNIFICANCE: White noise can be useful for clinical P3a applications, as it
      removes the variability of stimulus novelty.

PMID- 16564204
TI  - Differentiation between neurogenic and myogenic lesions of facial muscles by
      turn/amplitude analysis.

PMID- 16564205
TI  - Correlates of eye blinking as determined by synthetic aperture magnetometry.
AB  - OBJECTIVE: To evaluate the spatiotemporal characteristics of ocular and cerebral
      current sources during voluntary eyeblinking. METHODS: Whole-head
      magnetoencephalographic (MEG) recordings were acquired during voluntary blinking
      in eight healthy adults and analysed using synthetic aperture magnetometry (SAM).
      RESULTS: Fronto-temporal MEG sensors showed a large slow wave lasting
      approximately 400 ms and a small burst of activity with frequencies above 30 Hz
      at the initiation of the blink. Group maps of blink-related oscillatory activity
      at frequencies between 1-18 Hz and 32-64 Hz showed increased activity in and
      around the orbits during the 400 ms following blink onset. Increased oscillatory
      activity occurred in occipital regions 200 ms after blink onset at frequencies
      between 18 and 64 Hz. CONCLUSIONS: Blink-related MEG signals are recorded in the
      regions of the eyes and in the occipital cortex. The anterior activation is
      likely a combination of muscle contraction and eyelid currents. Occipital
      activation likely represents neural processes concerned with re-establishing the
      visual image after transient ocular occlusion. SIGNIFICANCE: The possibility of
      eyeblink-related fields should be considered when interpreting frontal and
      occipital source activities during SAM analyses.

PMID- 16564206
TI  - Reliability of motor cortex transcranial magnetic stimulation in four muscle
      representations.
AB  - OBJECTIVE: Motor cortex plasticity may underlie motor recovery after stroke.
      Numerous studies have used transcranial magnetic stimulation (TMS) to investigate
      motor system plasticity. However, research on the reliability of TMS measures of
      motor cortex organization and excitability is limited. We sought to test the
      reliability of these TMS measurements. METHODS: Twenty healthy volunteers were
      tested twice over a two-week period using TMS to determine motor threshold, map
      topography, and stimulus-response curves for first dorsal interosseous (FDI),
      abductor pollicis brevis (APB), extensor digitorum communis (EDC), and flexor
      carpi radialis (FCR) muscles. RESULTS: We found moderate to good test-retest
      reliability TMS measurements of motor threshold (ICC=0.90-0.97), map area
      (ICC=0.63-0.86) and location (ICC=0.69-0.86), and stimulus-response curves
      (ICC=0.60-0.83). CONCLUSIONS: TMS assessments of motor representation size,
      location, and excitability are generally reliable measures, although their
      reliability may vary according to the muscle under investigation. SIGNIFICANCE:
      These results suggest that TMS measurements of motor cortex function are reliable
      enough to be potentially useful in investigation of motor system plasticity.

PMID- 16564207
TI  - Treatment of depression in patients with restless legs syndrome: what is evidence
      based?

PMID- 16564208
TI  - Does size or frequency really matter?

PMID- 16564209
TI  - Hydrotherapy and conventional physiotherapy improve total sleep time and quality
      of life of fibromyalgia patients: randomized clinical trial.
AB  - OBJECTIVE: To compare hydrotherapy (HT) and conventional physiotherapy (CP) in
      the treatment of fibromyalgia (FM), regarding quality of life (QOL), total sleep
      time (TST), and total nap time (TNT). METHODS: Fifty outpatients, all female, 30
      60 years old, diagnosed with FM, were randomly assigned to two groups to carry
      out 3 weeks of treatment with HT or CP. In the beginning and in the end of
      treatment, patients were evaluated with the SF-36 questionnaire to measure QOL
      and the sleep diary for TST and TNT. Data analyses were blind. RESULTS: All 24 HT
      patients increased 1h in TST compared to 19 CP patients. TNT decreased in the HT
      group. QOL improved for the two groups in all domains when pre- and post
      intervention were compared, but there was no difference between groups.
      CONCLUSION: HT is more effective than CP to improve TST and to decrease TNT in FM
      patients.

PMID- 16564210
TI  - Simple interventions improve re-attendance when treating the sleep apnoea
      syndrome.
AB  - BACKGROUND AND PURPOSE: Interventions to improve treatment outcomes in sleep
      apnoea-hypopnoea syndrome (SAHS) have had mixed success. Most have concentrated
      on following the use of a continuous positive airway pressure (CPAP) machines;
      poorer users may not return for machine readings, so any compliance study must
      take into account rates of attendance rates. We hypothesised that a series of
      additional, early support measures would improve re-attendance over a sustained
      period. PATIENTS AND METHODS: Prospective, single-blinded interventional study.
      Seventy-two consecutive patients starting CPAP for SAHS were randomised to
      receive standard follow-up or extra early support. Attendance rates, CPAP use,
      Epworth scores, side-effects scores and number of changes to equipment were
      compared, by intent to treat, in both groups at 1 and 12 months. RESULTS: Re
      attendance rates were higher in the intervention group at 1 month (P=0.04), 6
      months (P=0.07) and 12 months (P=0.12). Those who defaulted tended previously to
      be poor users of the CPAP machine. For those who re-attended there was no
      difference in machine use or other outcomes. CONCLUSIONS: Simple interventions
      while commencing CPAP improve re-attendance with maximal benefit early on. This
      could provide more opportunities for solving problems early or considering
      alternative treatments. By confirming that poorer CPAP users eventually have
      higher default rates we recommend that future studies on CPAP compliance should
      first account for re-attendance rates.

PMID- 16564211
TI  - Erythrocyte deformability, plasma viscosity and oxidative status in patients with
      severe obstructive sleep apnea syndrome.
AB  - BACKGROUND AND PURPOSE: In patients with severe obstructive sleep apnea syndrome
      (OSAS), diurnal changes of plasma viscosity and erythrocyte deformability were
      measured to elucidate the possible mechanism of cardiovascular diseases in OSAS
      patients. PATIENTS AND METHODS: Plasma viscosity and erythrocyte deformability
      was determined in 11 OSAS patients and 11 healthy subjects matched by sex and
      age. Plasma viscosity was measured by a cone-plate viscometer, and erythrocyte
      deformability was determined by filtration technique. Whole blood counts were
      performed and oxidative status of the patients' plasma and erythrocytes were
      evaluated. RESULTS: OSAS patients had higher plasma viscosity than controls, both
      in the morning (1.74+/-0.3 vs. 1.36+/-0.2 mPas, P<0.002) and evening (1.55+/-0.2
      vs. 1.27+/-0.1 mPas, P<0.002), and morning plasma viscosity was significantly
      higher than the evening level (P<0.05). Morning plasma viscosity of patients was
      inversely correlated with their mean nocturnal SaO(2). Morning plasma
      malonyldialdehyde level was significantly higher in the patients than in the
      controls (69.7+/-30.5 vs. 45.5+/-11.0 nmol/l, P<0.005). Erythrocyte deformability
      of the patients was slightly lower. CONCLUSIONS: We have observed that plasma
      viscosity is high both in the morning and in the evening in severe OSAS patients.
      This elevation may predispose OSAS patients to myocardial infarction and stroke
      by increasing blood viscosity. Low nocturnal mean SaO(2) may be responsible for
      the high plasma viscosity in these patients.

PMID- 16564212
TI  - The effect of methylphenidate on the sleep-wake cycle of brain-injured patients
      undergoing rehabilitation.
AB  - BACKGROUND AND PURPOSE: A number of neuro-stimulants are routinely used as part
      of post-acute care of hospitalized brain-injured patients. To our knowledge, the
      effect of these stimulants on the sleep-wake cycles of brain-injured patients
      undergoing rehabilitation has not been addressed. We examined the effect of one
      of the most commonly used neuro-stimulants, methylphenidate, on the sleep-wake
      behavior of brain-injured patients undergoing rehabilitation at a dedicated brain
      injury clinic. PATIENTS AND METHOD: For this study, records of patients admitted
      between January and December 1999 were scrutinized retrospectively for the data
      on observationally defined sleep-wake distribution. A total of 30 patients
      diagnosed with traumatic brain injury were identified as having been observed for
      a full 24h a day for at least 10 days. Some of these patients (n=17) were
      administered methylphenidate on clinical grounds. They served as the experimental
      group, while the unmedicated patients (n=13) served as controls. For the present
      analysis, the sleep-wake cycles were arbitrarily designated as nighttime and
      daytime, respectively. A cumulative sleep-wake quantity in a 24-h period was also
      observed. RESULT: The average number of hours of sleep during a 24-h period was
      not significantly different for the two cohorts. Similar trends emerged for the
      nighttime and daytime observations. On the whole, methylphenidate appears not to
      have unfavorable effects on sleep-wake cycles, presently defined as nighttime,
      daytime and 24-h, in the traumatic brain injury population. CONCLUSION: This
      study sought to gain better understanding of the effect of methylphenidate on
      daytime sleepiness and nighttime sleep, and the data suggest that administration
      of methylphenidate does not appear to have an adverse effect on sleep-wake
      quantity.

PMID- 16564213
TI  - Nocturia in sleep-disordered breathing.
AB  - BACKGROUND AND PURPOSE: Nocturia is a common complaint in sleep-disordered
      breathing (SDB), but there is no study demonstrating the prevalence and frequency
      of nocturnal urination in a large number of SDB patients. To determine the
      prevalence and frequency of nocturnal urination among patients with SDB of
      different severities and to discover the factors related to nocturia. METHOD: A
      retrospective chart review was conducted among 1970 SDB patients. Nocturia was
      assessed using a standard questionnaire. Four groups of SDB patients were
      compared with regard to frequency of nocturnal urination and additional
      demographic, clinical, and polysomnographic (PSG) variables, by analysis of
      variance (ANOVA) with Tukey's honest significant difference (HSD) post-hoc
      comparisons. Partial correlation analysis was performed to detect the
      relationships between frequency of nocturnal urination and PSG and demographic
      variables. Logistic regression analysis was employed to examine the independent
      predictors of nocturia. RESULTS: Significant correlations were found between the
      frequency of nocturnal urination and mean age, body mass index (BMI), respiratory
      disturbance index (RDI), apnea-hypopnea index (AHI), respiratory effort index
      (REI) and lowest oxygen saturation. The frequency of nocturnal urination showed
      significant differences between four groups of individuals with SDB (P<0.001).
      Nocturnal urination of more than three episodes per night was reported
      significantly more by severe SDB patients (P<0.001). CONCLUSION: Age, BMI,
      hypertension (HT), AHI, and REI were found to be significantly associated with
      nocturia.

PMID- 16564214
TI  - Half of patients with obstructive sleep apnea have a higher NREM AHI than REM
      AHI.
AB  - BACKGROUND AND PURPOSE: To determine the percentage of sequential patients with
      obstructive sleep apnea with a higher non-rapid eye movement (NREM) apnea
      hypopnea index (AHI) than rapid eye movement (REM) AHI and those with a higher
      REM AHI than NREM AHI, and to look for factors that might influence the AHI to be
      higher in one of these two groups versus the other and thus ascertain the factors
      that cause an AHI to be higher in NREM than REM. A high body mass index (BMI) and
      a supine body position are well known as exacerbating factors for obstructive
      sleep apnea (OSA). Males, as well as older individuals, are generally more
      predominantly affected with OSA than females. Usually OSA is worse in REM sleep
      than in NREM sleep, although this is not always true. METHODS: A retrospective
      study of sequential patients from one month's admission to a single sleep
      laboratory was conducted. We determined the age, sex, BMI, body position,
      duration of apnea, amount of time spent in REM and oxygen desaturation in
      patients who had a higher NREM AHI than REM AHI versus those who had a higher REM
      AHI than NREM AHI. To minimize variability, the sleep studies were scored by a
      single individual. RESULTS: A higher NREM AHI than REM AHI was found in 50% of
      the 66 patients with OSA. Males predominated in each group and there was no age
      difference between the groups. Although AHI for both groups tended to become
      higher with an increase in BMI, the BMI was not statistically different between
      the two experimental groups. OSA was worse in the supine position in both
      experimental groups consistent with previous literature. Percentage of time spent
      in REM or the duration of the apnea did not determine whether a patient fell into
      the NREM AHI>REM AHI group versus the REM AHI>NREM AHI. The severity of oxygen
      desaturation was not significantly different between the NREM AHI>REM AHI versus
      the REM AHI>NREM AHI group. However, when we combined and analyzed the two groups
      as a whole, the apneas were longer in REM, consistent with previous literature.
      CONCLUSIONS: Although it is well known that OSA is generally worse in REM sleep
      because of the degree of desaturation and duration of apnea, a higher NREM AHI
      than REM AHI is found in up to one half of individuals. Most of the usual
      predictors for severity of OSA as a whole did not discriminate these groups.
      Further work needs to be done to determine the factors that discriminate these
      two groups and thus make AHI higher in NREM than REM.

PMID- 16564215
TI  - Circadian changes in CSF dopaminergic measures in restless legs syndrome.
AB  - BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) has a circadian component
      with symptoms being prominent at night. The dopaminergic (DAergic) system, which
      plays a role in RLS, entails circadian changes that parallel RLS symptom changes.
      The aim of this study was to look for relative and diurnal differences in DAergic
      activity. PATIENTS AND METHODS: All RLS subjects were treated prior to their
      enrollment in the study but were all drug-free for at least 2 weeks prior to
      evaluation. Cerebrospinal fluid (CSF) collected at 10 p.m. was used to determine
      DA-related co-factors and metabolites. These were compared to CSF values
      collected in a previous study at 10 a.m. RESULTS: The only significant finding
      from the 10 p.m. samples (30 RLS; 22 control) was increased 3-ortho-methyldopa
      (3OMD) for RLS compared to controls. A comparison of the 10 p.m. to 10 a.m.
      values (16 RLS; 9 controls) showed small, non-significant diurnal changes for
      controls but large diurnal changes in tetrahydrobiopterin (BH4), HVA:5HIAA ratio
      and 3OMD for RLS, with the 10 a.m. sample showing increases in all three CSF
      factors compared to the 10 p.m. sample. CONCLUSIONS: The greater diurnal changes
      in RLS suggest greater fluctuations than normal in DAergic circadian dynamics.
      The increased 3OMD concentration in the absence of concurrent exogenous levodopa
      (l-dopa) suggests changes in synthesis or metabolism of l-dopa in RLS.

PMID- 16564216
TI  - Reciprocal interactions between spontaneous and respiratory arousals in adults
      with suspected sleep-disordered breathing.
AB  - BACKGROUND AND PURPOSE: Excessive daytime sleepiness (EDS) is a major consequence
      of sleep-disordered breathing (SDB) in adults. In snoring children, spontaneous
      and respiratory arousals display reciprocal interactions, allowing for
      development of a new quantitative measure, the sleep pressure score (SPS), which
      provides intra-polysomnographic estimates of sleep pressure/disruption. The aim
      of the present study was to assess the interactions between respiratory and
      spontaneous arousals in adults with suspected SDB, and to examine whether the SPS
      and the Epworth sleepiness scale (ESS) are correlated. PATIENTS AND METHODS:
      Retrospective chart review of 530 adult patients who underwent polysomnographic
      evaluation for suspected SDB in two medical centers was performed.
      Polysomnographic studies reports, patients' demographics and ESS scores were
      reviewed. RESULTS: Spontaneous and respiratory arousal indices and the apnea
      hypopnea index (AHI) displayed negative and positive correlations respectively
      (r=-0.25, r=0.97, P<0.0001) indicating reciprocal interactions between
      respiratory and spontaneous arousals during sleep. The AHI corresponding to the
      SPS at which the respiratory arousal/total arousal fraction exceeded the
      spontaneous arousal/total arousal fraction occurred at approximately 14/h of
      total sleep time (TST) (compared to 7/h TST in children) (P<0.001). No
      correlation was found between SPS values and ESS scores. CONCLUSIONS: As in
      children, snoring adults exhibit reciprocal interactions between respiratory and
      spontaneous arousals that can also be expressed as a single quantitative measure,
      the SPS, which is highly dependent on the severity of SDB and could possibly
      serve as a more reliable index of sleep disruption, considering that the ESS is
      unrelated to either SPS or AHI.

PMID- 16564218
TI  - The Epworth sleepiness scale: relationship to sleep and mental disorders in a
      sleep clinic.
AB  - BACKGROUND AND PURPOSE: Both sleep disorders and mental disorders are associated
      with excessive daytime sleepiness as measured by the Epworth sleepiness scale
      (ESS). We sought to assess the relationship between the ESS scores and mental
      disorders in a sleep clinic. METHODS: One hundred sixty-five consecutive new
      referrals to a sleep clinic completed the ESS prior to their initial visit.
      Mental disorders (major depression, minor depression, anxiety not otherwise
      specified, and panic disorder) were diagnosed with the primary care evaluation of
      mental disorders (PRIME-MD) questionnaire, a reliable and valid instrument.
      Nearly all sleep diagnoses (95%) were made by polysomnography. RESULTS: The mean
      ESS for the cohort was 12.3 (standard deviation (SD) 5.1). There was no
      difference in the mean ESS for those with and without mental disorders (12.8 vs.
      12.2, P=0.48) or sleep-disordered breathing (SDB) (12.3 vs. 12.3, P=0.99). ESS
      scores were not different between patients with a comorbid mental disorder and
      SDB compared with the presence of a mental disorder or SDB alone (combination:
      13.0 vs. mental disorder: 11.5 vs. SDB: 12.2, P=0.70). There was also no
      relationship between ESS scores and the respiratory disturbance index (RDI)
      (P=0.63). CONCLUSIONS: We found no relationship between ESS scores and mental
      disorders among referrals to a sleep clinic. ESS cannot be used to screen for
      mental disorders among sleep clinic patients.

PMID- 16564217
TI  - Outcome of restless legs severity after continuous positive air pressure (CPAP)
      treatment in patients affected by the association of RLS and obstructive sleep
      apneas.
AB  - BACKGROUND AND PURPOSE: The association of obstructive sleep apnea syndrome
      (OSAS) and restless legs syndrome (RLS) has been reported in the literature for
      many years. Nevertheless, this pathological association has not yet been
      extensively studied and many questions remain unanswered. The primary concern of
      this study is to evaluate the influence of nasal continuous positive airway
      pressure (n-CPAP) therapy on daytime sleepiness and fatigue as well as the
      presence of a possible long-term beneficial effect on RLS severity and,
      secondarily, to ascertain the clinical, neurophysiological and polysomnographic
      characteristics of a group of patients with both OSAS and RLS. PATIENTS AND
      METHODS: All patients had a diagnostic polysomnography (PSG) and a second
      polysomnography for titration of n-CPAP. Laboratory tests (blood glucose, serum
      ferritin), body mass index (BMI) calculation and a neurophysiological evaluation
      (auditory P300 and electroneuromyography) were done. The Epworth Sleepiness Scale
      (ESS) and the Pichot's questionnaire of fatigue/depression (PIC) were applied to
      all patients before and after three months of n-CPAP treatment. The International
      Restless Legs Syndrome Study Group rating scale (IRLS) was applied before and
      after n-CPAP. Results were compared. RESULTS: The ESS scores decreased from
      10.64+/-4.83 at baseline to 7.41+/-3.5 (P<0.05). PIC scores decreased from
      16.65+/-7.27 to 10.12+/-6.40 (P<0.01). IRLS scores decreased from 17.60+/-7.11
      before to 12.52+/-9.25 after n-CPAP (P<0.05). CONCLUSIONS: Our findings suggest
      that not only fatigue and sleepiness but also the severity of RLS show a
      favorable response to n-CPAP in the group of patients with OSAS and RLS.

PMID- 16564220
TI  - Two legs, one heart, one sleeping brain.

PMID- 16564219
TI  - Urinary protein expression patterns in children with sleep-disordered breathing:
      preliminary findings.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is the most common form of sleep
      disordered breathing, with almost 15 million Americans affected and many more at
      risk. Current diagnostic approach to OSA requires polysomnography, which is
      laborious, onerous, and time-consuming. There is ample evidence that inflammatory
      responses to the perturbations associated with OSA trigger a variety of genes and
      signaling cascades that ultimately lead to end-organ injury and changes in kidney
      function and protein expression. The aim of this study was therefore to analyze
      proteins in human urine and assess whether differential expression of particular
      proteins is associated with the presence of OSA. METHODS: Eleven OSA and 11
      control children between the ages of three and 14 (males=17; females=5) underwent
      overnight sleep studies followed by a first-morning urine sample. Proteomic
      analysis of urine samples yielded a unique map of proteins, of which, five spots
      were selected for further analysis due to their significant intensity differences
      between OSA and control groups. RESULTS: Mass spectrometry followed by peptide
      mass fingerprinting conclusively identified four of the five spots as gelsolin,
      perlecan (a heparan sulfate proteoglycan), albumin, and immunoglobulin (P<0.05
      and protein scores>67). CONCLUSIONS: Overall, increased expression of gelsolin
      and perlecan in the urinary proteome of children with OSA suggests that the
      episodic hypoxia associated with OSA may lead to changes in protein permeability
      or alternatively to increased catabolism of these proteins and their excretion in
      urine.

PMID- 16564221
TI  - A preliminary study of psychological factors affecting patients' acceptance of
      CPAP therapy for sleep apnoea syndrome.
AB  - BACKGROUND: Many patients abandon continuous positive airway pressure (CPAP)
      treatment after initial acceptance. This may be for physical or psychological
      reasons. METHODS: We have carried out semi-structured interviews, constructed
      from the Health Belief Model (HBM) with a convenience sample of patients who had
      recently abandoned CPAP treatment after at least 6 months of use. We explored
      their understanding and experiences of their OSA and of the CPAP therapy and
      their reasons for stopping treatment. RESULTS: Nine patients were interviewed
      (age 32-70 years; 8 males). Four patients were not clear about the nature,
      severity, or consequences of sleep apnoea syndrome (SAS) and did not consider
      themselves to be ill. Three expected to be cured by the machine. Only one patient
      spoke of life-threatening risk. Eight of the nine patients had other health
      disorders. Seven stopped CPAP because of negative experiences, including problems
      with the mask and noise from the machine. Two patients felt 'liberated' on
      stopping treatment. CONCLUSIONS: Studies at the initiation stage of CPAP
      treatment are needed in order to identify factors impeding acceptance, which can
      be addressed early. The Health Belief Model, which emphasises subjective health
      experience and patients' beliefs about treatment, may be a useful tool for such
      investigations.

PMID- 16564222
TI  - Conservative non-pharmacological treatment options are not frequently used in the
      management of hip osteoarthritis.
AB  - Osteoarthritis (OA) is the most frequent joint disorder in seniors. Systematic
      reviews suggest that conservative treatment is effective and preferred in mild
      moderate cases. The objective of this study was to examine the proportion of
      patients receiving physiotherapy, exercise or walking aids, and to explore
      factors associated with their prescription. We conducted a retrospective survey
      of patients about to undergo total hip arthroplasty for hip osteoarthritis.
      Patients were asked about past prescriptions for cane use, physiotherapy and
      exercise. Of 161 patients (36.6% male, mean age 68.7+/-10.1 years), 76% were
      prescribed a cane (adherence=86.2%). The main reason for not using a cane was
      vanity. Of the 28.0% patients prescribed physiotherapy, 73.3% received exercises
      compared to only 2.6% of non-physiotherapy patients. Patients who were older or
      worked in manual labour were more likely to be prescribed a cane and less likely
      to be prescribed physiotherapy or exercises. Men were less likely than women to
      be prescribed all three, but only cane use was statistically significant across
      genders. In conclusion, physiotherapy and exercise are not commonly prescribed in
      patients with hip OA.

PMID- 16564223
TI  - Mosquito transgenesis: what is the fitness cost?
AB  - The generation of transgenic mosquitoes with a minimal fitness load is a
      prerequisite for the success of strategies for controlling mosquito-borne
      diseases using transgenic insects. It is important to assemble as much
      information as possible on this subject because realistic estimates of transgene
      fitness costs are essential for modeling and planning release strategies.
      Transgenic mosquitoes must have minimal fitness costs, because such costs would
      reduce the effectiveness of the genetic drive mechanisms that are used to
      introduce the transgenes into field mosquito populations. Several factors affect
      fitness of transgenic mosquitoes, including the potential negative effect of
      transgene products and insertional mutagenesis. Studies to assess fitness of
      transgenic mosquitoes in the field (as opposed to the laboratory) are still
      needed.

PMID- 16564225
TI  - Reproductive rights and HIV/AIDS.
AB  - Reproductive and sexual rights are at the centre of the acquired immunodeficiency
      syndrome (AIDS) epidemic through culturally defined gender roles, gender-based
      violence and limited access to quality health care. AIDS control is one of the
      Millennium Goals, and the '3-by-5' initiative [antiretroviral (ARV) therapy for
      all in need by 2005] is far from reaching its target. Apart from the reduction in
      morbidity and mortality due to antiretroviral (ARV) therapy, proven effective
      interventions for reproductive health include consistent condom use, voluntary
      counselling and testing, promoting earlier treatment and adhesion to preventative
      measures, and the use of ARV therapy, Caesarean section and bottle-feeding to
      reduce vertical transmission. The effectiveness of control of sexually
      transmitted infection is dependent on the maturity of the AIDS epidemic, but is
      an essential intervention due to other serious consequences for sexual and
      reproductive health. Male circumcision is a polemic preventive measure under
      debate, and microbicide products, a promising women-controlled method, are still
      undergoing efficacy trials. A reasonably organized and accessible health sector,
      the involvement of males in reproductive health debate and a gender-sensitive,
      rights-based political agenda, with ample participation of communities, are
      necessary for reproductive health interventions to move from proved efficacy to
      necessary effectiveness, putting evidence into practice.

PMID- 16564226
TI  - Sexual violence.
AB  - Gender-based violence is related to the power imbalance between men and women
      that is present, to a greater or lesser degree, in all societies. It was
      recognized as a human rights problem by the United Nations relatively recently.
      It includes emotional, physical and sexual violence. Sexual violence is the
      extreme form of gender-based violence, usually accompanied by the other types of
      violence. Its prevalence is difficult to determine, but it is likely to affect at
      least one-third of women at some time in their life. It has multiple effects on
      women's physical and gynaecological health, and these depend greatly on the
      quality of care that women receive immediately after the assault. Unfortunately,
      most emergency health services, including those in women's hospitals, are not
      prepared to provide the correct care for these women. Care should be
      multidisciplinary and should involve crisis treatment, meticulous clinical
      examination with complementary auxiliary methods, treatment of physical lesions,
      prevention of pregnancy and transmission of sexually transmitted infections, and
      follow-up for at least 6 months after the assault.

PMID- 16564227
TI  - Adenomyosis: the pathophysiology of an oestrogen-dependent disease.
AB  - Adenomyosis uteri is a common gynaecological disorder that is characterized by
      the presence of ectopic endometrial glands and stroma in the myometrium. Although
      adenomyosis and endometriosis are different diseases, both of them grow and
      regress in an oestrogen-dependent fashion. Polymorphisms in the oestrogen
      receptor alpha gene are associated with a risk of adenomyosis. Adenomyotic tissue
      contains steroid receptors as well as aromatase and sulphatase enzymes. Together
      with the circulating oestrogen, locally produced oestrogens stimulate the growth
      of tissue mediated by the oestrogen receptors. Oestrogen metabolism, including
      the expression pattern of aromatase and the regulation of 17beta-hydroxysteroid
      dehydrogenase type 2 is altered in the eutopic endometrium of women with
      endometriosis, adenomyosis, and/or leiomyomas compared to that in the eutopic
      endometrium of women without disease. In addition to the conventional hormonal
      treatment with gonadotropin-releasing hormone agonists and danazol, the use of
      steroid-releasing intrauterine devices may be applicable to clinics.

PMID- 16564228
TI  - Spectrum of MR features in adenomyosis.
AB  - Magnetic resonance (MR) imaging is a highly accurate non-invasive technique for
      the diagnosis of adenomyosis. Typical MR features include either diffuse or focal
      thickening of the junctional zone or an ill-defined area of low signal intensity
      in the myometrium on T2-weighted MR images. Occasionally, the islands of ectopic
      endometrial tissue can be identified as punctate foci of high signal intensity.
      Less commonly, adenomyosis can present as a well-circumscribed form known as
      adenomyoma, adenomyotic cyst characterized by the presence of haemorrhagic cyst,
      or adenomyomatous polyp protruding into the uterine cavity. The MR appearances of
      adenomyosis may occasionally fluctuate in response to hormonal stimulation and
      treatment. MR imaging is helpful not only in monitoring the treatment effect of
      hormonal therapy, but also in predicting therapeutic effect. In cases of
      endometrial cancer in the uterus with adenomyosis, evaluation of myometrial
      invasion may become difficult. Rarely, endometrial cancer may arise directly from
      adenomyosis resulting from malignant transformation of endometrial glands,
      creating diagnostic challenges. Differential diagnosis of adenomyosis on MR
      imaging include physiological myometrial contraction and almost all myometrial
      lesions, and they should be carefully differentiated from adenomyosis by
      identifying typical clinical and MR features in these lesions. Precise knowledge
      of the spectrum of MR features in adenomyosis greatly helps in determining an
      accurate diagnosis and appropriate management of the patients.

PMID- 16564229
TI  - Eradication of p53-mutated head and neck squamous cell carcinoma xenografts using
      nonviral p53 gene therapy and photochemical internalization.
AB  - Photochemical internalization (PCI) technology has been used for PEI-mediated p53
      gene transfer in mice bearing head and neck squamous cell carcinoma (HNSCC)
      xenografts. Using luciferase as a reporter gene, PCI led to a 20-fold increase in
      transgene expression 48 h after transfection and sustained transgene expression
      for 7 days. Therefore, iterative p53 gene transfer was performed by means of a
      weekly single injection of PEIGlu4/p53 complexes alone or with PCI for 5 (group
      A) or 7 (group B) weeks. The efficiency of p53 gene therapy was evaluated by
      following tumor growth and expression of P53-related downstream proteins (P21,
      MDM2, Bcl2, Bax). Apoptosis induction was evidenced through caspase-3 activation
      and PARP cleavage. Using PCI, tumor growth inhibition was observed in all
      transfected animals. Further, successful tumor cure was achieved in 17% (group A)
      and 83% (group B) of animals. PCI-mediated p53 gene transfer led to higher P53
      protein expression that was correlated with induction of Bax and P21 proapoptotic
      proteins, repression of Bcl2 as well as activation of caspase-3, and cleavage of
      PARP. The present study demonstrates that PCI enhances the in vivo efficiency of
      PEI-mediated p53 gene transfer and can be proposed for p53 gene therapy in HNSCC.

PMID- 16564230
TI  - Abolishing Bax-dependent apoptosis shows beneficial effects on spinal muscular
      atrophy model mice.
AB  - Spinal muscular atrophy (SMA) is the most common genetic motoneuron degenerative
      disorder, but the mechanism(s) of motoneuron degeneration is unclear. We
      previously generated SMA model mice, which genotypically and phenotypically
      mimicked human SMA patients, by a combination of knockout and transgenic
      techniques. Here, we used these SMA model mice to decipher the apoptotic
      mechanism(s) involved in SMA motoneuron degeneration. We found a significant
      increase in proapoptotic Bax expression in the spinal cords of SMA mice in
      comparison with their wild-type littermates. After crossing SMA mice with Bax
      knockout mice, we produced in vivo evidence indicating that Bax protein plays an
      important role in the degeneration of SMA spinal motoneurons. Progeny Bax
      deficient SMA mice showed milder disease severity, longer life spans, and
      significant increases in spinal motoneuron densities compared to SMA littermates
      with wild-type Bax genes. Our results strongly suggest that suppression of Bax
      involved apoptosis has the potential for amelioration of SMA.

PMID- 16564231
TI  - Use of strain and tissue velocity imaging for early detection of regional
      myocardial dysfunction in patients with beta thalassemia.
AB  - BACKGROUND AND AIM OF STUDY: Iron overload contributes to cardiac dysfunction in
      patients with beta thalassemia (Th). Tissue velocity and strain imaging (TVI and
      SI) might prove useful in early detection of regional myocardial dysfunction in
      these patients. The aim of this study is to clarify the value of TVI and SI in
      early detection of regional myocardial dysfunction in thalassemia patients.
      METHODS AND RESULTS: This study included two age-matched groups; G1: 27 Th
      patients and G2: 14 normal subjects. Conventional echo-Doppler measures of LV and
      RV dimensions and function were obtained. TVI measures included systolic and
      diastolic myocardial velocities (Sm, Em, Am and Em/Am) of the basal segments of
      septal wall, lateral LV and RV free walls. Systolic strain values were measured
      in the same basal segments and included S-septal, S-LV and S-RV. Strain and TVI
      data were compared in the two groups. Sm and strain values were compared in the
      different walls (LV, RV and septum) in each group separately. S-LV was lower in
      G1 than G2 (20.9 +/- 6.8 vs 27.2 +/- 4.3, p < 0.001), while S-septal was higher
      in G1 than G2 (31.1 +/- 8.3 vs 25.1 +/- 3.8, p < 0.01). TVI measures of diastolic
      performance of the septal and RV walls were different in G1 compared to G2.
      Septal-Em was lower, septal-Am was higher and septal-Em/Am was lower in G1
      compared to G2. RV-Am was higher and RV-Em/Am was lower in G1 compared to G2.
      Other SI and TVI measures were not significantly different in G1 from G2. Sm and
      strain values were lower in the lateral LV wall compared to septal wall in G1 but
      not in G2, while the corresponding values of the RV wall were higher than those
      of the septal and LV walls in both groups (G1 and G2). CONCLUSION: Thalassemia
      patients have regional systolic dysfunction in the lateral LV wall and regional
      diastolic dysfunction in the septal and RV wall. TVI and the newer modality SI
      are promising tools for quantitative assessment of regional myocardial function.
      SI seems more capable of early detection of regional myocardial dysfunction.

PMID- 16564232
TI  - Can the left ventricular early diastolic tissue-to-blood time interval be used to
      identify a normal pulmonary capillary wedge pressure?
AB  - The pulsed Doppler early diastolic left ventricular (LV) tissue (e)-blood (E)
      onset temporal relationship (e-E) is suggested to predict pulmonary capillary
      wedge pressure (PCWP), through the formulas: tau = 32 + 0.7(e-E) and PCWP = LV
      end-systolic pressure x e(-IVRT/tau). Small changes/errors in E could influence
      the quotient IVRT/tau by oppositely affecting IVRT and e-E. At rest in 50 healthy
      individuals we noted: e-E: 2 +/- 14 ms; IVRT: 89 +/- 17 ms; calculated tau: 33 +/
      10 ms; and PCWP: 9 +/- 9 mmHg (> 12 mmHg in 28%). Non-pharmacological preload
      alterations in 14 individuals rendered an intraindividual 'PCWP'-fluctuation of
      up to 40 mmHg. This application may therefore not be clinically robust.

PMID- 16564233
TI  - Biomedical informatics training at Stanford in the 21st century.
AB  - The Stanford Biomedical Informatics training program began with a focus on
      clinical informatics, and has now evolved into a general program of biomedical
      informatics training, including clinical informatics, bioinformatics and imaging
      informatics. The program offers PhD, MS, distance MS, certificate programs, and
      is now affiliated with an undergraduate major in biomedical computation. Current
      dynamics include (1) increased activity in informatics within other training
      programs in biology and the information sciences (2) increased desire among
      informatics students to gain laboratory experience, (3) increased demand for
      computational collaboration among biomedical researchers, and (4) interaction
      with the newly formed Department of Bioengineering at Stanford University. The
      core focus on research training-the development and application of novel
      informatics methods for biomedical research-keeps the program centered in the
      midst of this period of growth and diversification.

PMID- 16564234
TI  - Selectivity and sensitivity of a reagentless electrochemical DNA sensor studied
      by square wave voltammetry and fluorescence.
AB  - Poly(5-hydroxy-1,4-naphthoquinone-co-5-hydroxy-3-thioacetic acid-1,4
      naphthoquinone)-modified electrode is used for the direct electrochemical
      detection of oligonucleotide hybridization. The polymer film presents well
      defined electroactivity in the cathodic potential domain (between 0 and -0.8
      V/SCE), due to the quinone group embedded into the polymer structure. The
      detection can be performed simply by square wave voltammetry. This sensor is a
      "signal-on" device and works with different oligonucleotide lengths, from 10 to
      30 bases. Quantitative results from fluorescence are consistent with
      electrochemical data. It is confirmed that the signal increase in square wave
      voltammetry is unambiguously due to hybridization. The biosensor presents a
      detection limit of target of ca. 25 nM and is highly selective as it can
      discriminate single mismatch base.

PMID- 16564235
TI  - Resorption of auditory ossicles and hearing loss in mice lacking osteoprotegerin.
AB  - Bones conduct sound in the middle ear. The three ossicles-the malleus, incus, and
      stapes-form a chain that transmits vibrations from the tympanic membrane to the
      oval window of the inner ear. Little is known about bone remodeling events in
      these ossicles and about potential effects of osteoporosis on hearing loss.
      Osteoclastic bone resorption is enhanced in Opg(-/-) mice lacking
      osteoprotegerin, which is a soluble decoy receptor for the osteoclastogenic
      cytokine RANKL. We asked whether auditory ossicles are resorbed in Opg(-/-) mice,
      and whether these mice suffer from impaired auditory function. All three ossicles
      in Opg(-/-) mice showed thinning, especially at the malleal manubrium and incus
      body. Most notably, unlike in the case in wild-type mice, the junction between
      the stapes and the otic capsule was fixed in Opg(-/-) mice, and the stapedial
      footplate was thinner and broader. Radiological analyses revealed that malleal
      cortical thickness was positively correlated with tibial bone mineral density in
      Opg(-/-) and control littermate mice. Furthermore, progressive hearing loss was
      detected in Opg(-/-) mice starting at 6 to 15 weeks of age. These data suggest
      that osteoprotegerin plays a crucial role in hearing by protecting the auditory
      ossicles and otic capsule from osteoclastic bone resorption.

PMID- 16564236
TI  - A rare intrapericardial enterogenous cyst presenting in infancy.
AB  - We report an infant with an intrapericardial enterogenous cyst, and discuss the
      differential diagnosis of intrapericardial cysts presenting in infancy.

PMID- 16564237
TI  - Left ventricular bronchogenic cyst.
AB  - Bronchogenic cysts occurring in the left ventricle are a medical rarity. One
      successfully operated case is reported herein. The location of the cyst was just
      between the epicardium and myocardium of the inferior left ventricular wall,
      adjacent to the apex of the heart. Complete excision was achieved through a left
      anterolateral thoracotomy without extracorporeal circulation.

PMID- 16564238
TI  - Ethics guidelines for destination therapy.
AB  - The introduction of the left ventricular assist device as a destination therapy
      for patients with heart failure introduces several ethical issues. These issues
      are discussed to help destination therapy teams design ethically sound policies
      and procedures. This article addresses ethical issues pertaining to informed
      decision making, device failure, and change out, as well as guidelines for
      deactivation, fair employment of medical and psychosocial criteria, the nature of
      destination therapy as an elective end-of-life therapy, and advance care planning
      strategies.

PMID- 16564239
TI  - Smoking status as a prognostic factor in patients with stage I pulmonary
      adenocarcinoma.
AB  - BACKGROUND: Cigarette smoking is a well-known risk factor for lung
      carcinogenesis; however, its effect on tumor progression is still unclear. We
      herein investigated the influence of cigarette smoking on postoperative prognosis
      in patients with non-small cell lung cancer (NSCLC). METHODS: The postoperative
      survival and pathologic stage of 999 patients with NSCLC who underwent a curative
      resection were retrospectively investigated in relation to the pack-year index
      (PYI). RESULTS: Adenocarcinoma patients with a PYI of less than 20 showed a more
      favorable prognosis than those with a PYI of 20 or more, whereas no difference
      was observed among the subgroups of squamous cell carcinoma patients. In
      adenocarcinoma, stage I disease was a significantly larger population in never
      smokers than in smokers. A multivariate analysis revealed that the smoking habit
      (yes or no) and stage (IA or IB), but not gender or histologic subtype
      (bronchioloalveolar type or not), are independent prognostic factors in stage I
      adenocarcinoma with hazard ratios of 1.8 and 2.3, respectively. CONCLUSIONS: The
      smoking status is a significant prognostic factor for stage I pulmonary
      adenocarcinoma.

PMID- 16564240
TI  - Invited commentary.

PMID- 16564241
TI  - Pathologic and biological assessment of lung tumors showing ground-glass opacity.
AB  - BACKGROUND: We evaluated the pathologic and biological aspects of lung tumors 3.0
      cm or less in diameter with the appearance of ground-glass opacity (GGO).
      METHODS: Of 988 patients with non-small cell lung cancer who underwent operations
      at our institute between January 1994 and December 2004, 87 resected lung tumor
      specimens that showed GGO appearance on helical computed tomography were obtained
      from 81 patients. Forty-four lesions were pure GGO with no solid component in the
      tumor and 43 lesions were mixed GGO consisting of areas of attenuation with a
      solid component. Together with histological features, MIB1 and nm23 expression
      within tumors were examined immunohistochemically. RESULTS: The mean tumor size
      in the pure GGO group was significantly smaller than that in the mixed GGO group.
      The composition of pathologic subtypes and biological characteristics were
      clearly different between the two groups. Although atypical adenomatous
      hyperplasia and localized bronchioloalveolar cell carcinoma of Noguchi's A and B
      were the predominant pathologic subtypes and nm23 negativity was rare in the pure
      GGO group, a high score for expression of MIB1 was often found in pure GGO tumors
      even though the tumors were less than 10 mm in diameter. CONCLUSIONS: If the
      tumor is 2 cm or less in diameter, the ability of invasion and metastasis seems
      to be low in pure GGO tumors. However, the proliferation ability of these tumors
      suggests the necessity of a careful follow-up schedule if the tumor is greater
      than 5 mm in diameter. For mixed GGO tumors, surgical resection instead of
      observation is justified.

PMID- 16564242
TI  - Invited commentary.

PMID- 16564243
TI  - Techniques of reconstruction for inadequate donor left atrial cuff in lung
      transplantation.
AB  - BACKGROUND: An inadequate donor left atrial (LA) cuff due to an anatomical
      abnormality of the pulmonary vasculature or technical errors at the time of
      procurement can exclude the lungs from transplant. This study aims to describe
      the incidence, efficacy, and various techniques of LA cuff reconstruction in lung
      transplantation. METHODS: A total of 637 pulmonary venous anastomosis in 405
      consecutive lung transplants from January 1995 to July 2005 were reviewed.
      Comparison between the patients who required LA cuff reconstruction
      (reconstruction group) or who did not (no-reconstruction group) was made in
      posttransplant outcomes. RESULTS: An overall incidence of requirement of LA cuff
      reconstruction was 2.7% (4% on the right, 1% on the left, p = 0.03). Seventy-one
      percent of LA inadequacy was corrected using a pericardial patch on the anterior
      LA cuff wall; the remainder required complicated reconstruction for
      separated/short pulmonary veins to create a new LA cuff. There was no significant
      difference between the reconstruction and no-reconstruction groups, respectively,
      in oxygenation (329 +/- 28, 337 +/- 10, p = 0.81), duration of intubation and
      intensive care unit stay (p = 0.54, p = 0.89, respectively), 30-day mortality
      (12%, 6%, p = 0.30), and 5-year survival (57%, 52%, p = 0.80). CONCLUSIONS:
      Inadequate donor LA cuff is an infrequent but potentially serious complication in
      lung transplantation. Donor LA cuff reconstruction using donor pericardium or
      pulmonary artery remnant is a useful technique to salvage surgically marginal
      lungs without affecting early and late posttransplant outcomes. These lungs
      should not be excluded from transplantation.

PMID- 16564244
TI  - Ex vivo evaluation of human lungs for transplant suitability.
AB  - BACKGROUND: If lungs could be retrieved from non-heart-beating donors, the
      critical shortage of lungs for transplant could be alleviated. An obstacle to
      this approach is the inability to predict these lungs' suitability for
      transplant. We used human lungs deemed unsuitable for transplant to develop a
      method to perfuse and ventilate human lungs ex vivo to assess gas exchange and
      vascular resistance, and to perform bronchoscopic inspection and radiographic
      evaluation. METHODS: Lungs were retrieved from six brain-dead organ donors after
      cold Perfadex (Vitrolife, Kungsbacka, Sweden) flush, stored cold for 6 to 13
      hours (mean, 8.7 hours) then perfused and rewarmed in a modified cardiopulmonary
      bypass circuit. Circuit perfusate was buffered colloid-crystalloid containing
      type-specific leukocyte-filtered blood (hematocrit of 10%-12%), circulated
      through a membrane oxygenator ventilated with CO2 and nitrogen to deoxygenate it.
      Lungs were ventilated with fraction of inspired oxygen (Fio2) 0.5 when 32 degrees
      C was reached. Gas exchange and vascular resistance was assessed at 5 L/minute
      flow at 37 degrees C, Fio2 0.5 and 1.0. Bronchoscopy, plain radiographs, and
      spiral computed tomographic (CT) scans were performed. Lung biopsies were
      obtained pre- and post-reperfusion. RESULTS: Ex vivo perfusion did not cause
      increased wet to dry ratio, or major abnormalities by microscopy but was
      associated with elevated tissue levels of conjugated dienes. The alveolar
      arterial difference in partial pressure of oxygen (Pao2)/Fio2 ratio in the ex
      vivo circuit was generally higher than in the six donors. Ex vivo radiographs and
      CT scans were abnormal in all lungs, confirming unsuitability of these lungs for
      transplant. CONCLUSIONS: Ex vivo evaluation of human lungs is feasible and may be
      useful to evaluate transplant suitability of lungs retrieved after circulatory
      arrest from non-heart-beating donors.

PMID- 16564245
TI  - Non-Hodgkin's lymphoma presenting as a large chest wall mass.
AB  - BACKGROUND: Malignant lymphoma presenting as a solitary chest wall mass is not
      frequently seen. Only a few case reports have been found in the English
      literature. The treatment for primary chest wall lymphoma remains unclear.
      METHODS: From 1991 to 2004, of 157 patients with initial presentation of isolated
      chest wall mass, non-Hodgkin's lymphoma was diagnosed in 7 of them. Patients with
      tumors arising from axillary lymph nodes or mediastinal lymphadenopathy with
      chest wall extension were excluded in the study. The clinical manifestation,
      management, and outcome of these patients were reviewed. RESULTS: There were 1
      female and 6 male patients with a mean age of 66.5 years. The mean largest
      diameter of the mass was 10.3 cm. Four of these 7 patients had the chest wall
      lymphoma as the only site of disease. The other 3 patients had other organ
      involvement including lung, bone, or liver. The pathologic diagnoses were
      malignant lymphoma in 2 patients and diffuse large B-cell lymphoma in 5 patients.
      Three patients with chest wall lymphoma as the only site of disease had tumor
      excision followed by adjuvant chemotherapy. No recurrence or metastasis was noted
      for these 3 patients. The mean follow-up period was 102 months. The other patient
      with chest wall lymphoma as the only site of disease, who had chemotherapy as the
      initial treatment, remained free of disease for 6 months after treatment. The
      other 3 patients with other organ involvement who were managed with chemotherapy
      with or without radiotherapy died of disease after a mean survival of 20 months.
      CONCLUSIONS: Malignant lymphoma presenting as a large chest wall mass is not
      common. Although the primary treatment of choice for lymphoma with or without
      chest wall involvement is chemotherapy, surgery followed by adjuvant chemotherapy
      can provide satisfactory outcome for some patients in whom the chest wall
      lymphoma was the only site of disease.

PMID- 16564246
TI  - Invited commentary.

PMID- 16564247
TI  - Current surgical therapy for patients with tuberculous abscess of the chest wall.
AB  - BACKGROUND: Although anti-tuberculosis medication is essential for the treatment
      of tuberculous abscess of the chest wall, surgical treatment also plays an
      important role. We report our surgical experience for patients with tuberculous
      abscess of the chest wall. METHODS: The series was comprised of 16 patients with
      tuberculous abscess of the chest wall, and they were treated from May 1996 to
      June 2003 at St. Vincent's Hospital, Suwon, Korea. The data were retrospectively
      reviewed. RESULTS: Tuberculous abscesses were managed by combined anti
      tuberculosis medication and surgery of either abscess excision with rib resection
      (11 abscesses) or abscess excision alone (7 abscesses). The overall rate of rib
      involvement for abscess was 44.4 % (8 abscesses in 7 patients), and the rate of
      rib involvement was not much different according to the extent of the chest wall
      involvement. The incidence of performing a second surgical procedure was higher
      in the following groups: (1) the group with pathologic evidence of bone
      involvement (3 of 7 patients vs 1 of 9 patients), (2) the group that was not
      given preoperative anti-tuberculosis medication (4 of 7 patients vs none of 9
      patients). CONCLUSIONS: In managing tuberculous abscess of the chest wall,
      extensive abscess excision with rib resection is considered to be important.
      Preoperative anti-tuberculosis medication may play an important role in reducing
      the postoperative complication, including abscess recurrence.

PMID- 16564248
TI  - One-year follow-up after thoracoscopic sympathectomy for hyperhidrosis: outcomes
      and consequences.
AB  - BACKGROUND: Thoracic sympathectomy is recognized as an effective treatment for
      patients with severe hyperhidrosis. While good early results have been
      documented, continuing efficacy and patient satisfaction has not been well
      defined. We reviewed our results in patients who were at least one year out from
      surgery. METHODS: All procedures were performed thoracoscopically using bilateral
      3 mm ports and excision of a segment of the sympathetic chain by electrocautery.
      The level of sympathectomy depended upon clinical symptoms: T2 for face/scalp, T3
      for palmar hyperhidrosis, and T4 for axillary hyperhidrosis, or a combination of
      levels for multiarea sweating. All patients were followed-up at least 1 year
      postprocedure by mail questionnaire and/or telephone. RESULTS: Two hundred twenty
      two patients had undergone thoracoscopic sympathectomy for essential
      hyperhidrosis between Jan 1, 2002 and Nov 30, 2003, with 170 patients having at
      least one-year follow-up. The patients' preoperative assessment of the severity
      of sweating in the affected areas was compared with their one-year evaluation in
      order to determine the durability of the procedure. All affected areas continued
      to show significant improvement in sweating as compared with preoperative
      symptoms. Compensatory sweating was reported in 85% of our patients at one-year
      follow-up. Patients with a T2 lesion were significantly more likely to have
      severe compensatory sweating than those with other levels; 48.8% vs 16.1% (p <
      0.001). Patients with levels other than T2 reported high degrees of satisfaction
      unrelated to their postoperative compensatory symptoms. CONCLUSIONS: Patient
      satisfaction and perceived effectiveness with sympathectomy for palmar or
      axillary hyperhidrosis remain high even one year after the procedure. Inclusion
      of the T2 lesion results in significantly more severe compensatory sweating and
      reduced satisfaction than other levels.

PMID- 16564249
TI  - Endothelial nitric oxide synthase is essential for postpneumonectomy compensatory
      vasodilation.
AB  - BACKGROUND: After pneumonectomy, the remaining lung vasculature must vasodilate
      to compensate for increased blood volume. We hypothesized that endothelial nitric
      oxide synthase (eNOS) is essential for compensatory vasodilation after
      pneumonectomy. METHODS: Adult, wild-type C57BL6 (WT) and eNOS knockout (eNOS-/-)
      mice underwent left pneumonectomy and recovered under normoxic conditions.
      Animals were lightly anesthetized at 1, 3, 7, or 14 days after pneumonectomy, and
      closed chest, systolic right ventricular pressure (RVP) was recorded using fine
      needle cannulation. The right ventricle to left ventricle plus septum weight
      ratios were measured as an index of right ventricular hypertrophy. Two additional
      groups of mice (WT and eNOS-/-) were recovered after pneumonectomy in inhaled
      nitric oxide (iNO, 10 ppm), and RVP was measured on day 7. RESULTS: The eNOS-/-
      mice had significantly higher preoperative RVP than did WT (17.1 +/- 0.4 versus
      14.2 +/- 0.2 cmH2O, p = 0.001). Both groups exhibited transient periods of
      pulmonary hypertension after pneumonectomy. On day 1, RVP was 80% above baseline
      in eNOS-/- mice (30.7 +/- 0.8 cmH2O) versus 42% in WT mice (20.2 +/- 0.7 cmH2O, p
      = 0.0001). The RVP returned to baseline in WT mice (16.3 +/- 0.2 cmH2O) but
      remained significantly elevated in eNOS-/- mice (28.6 +/- 0.9 cmH2O) at day 3 and
      at each time thereafter (p = 0.0001). The iNO significantly reduced RVP in eNOS-/
      animals to 15.2 +/- 0.3 cmH2O (p = 0.0001) while having no effect in WT animals.
      Right ventricular hypertrophy was not observed in any group. CONCLUSIONS:
      Pneumonectomy results in a transient increase in RVP. Under normal circumstances,
      these pressures return to baseline within 3 days. The eNOS-/- mice failed to
      display compensatory vasodilation yet could be rescued with iNO. These results
      suggest that eNOS is essential for postpneumonectomy compensatory vasodilation.

PMID- 16564250
TI  - Initial impact of drug-eluting stents on coronary artery bypass graft surgery.
AB  - BACKGROUND: Drug-eluting stents (DES) reduce the incidence of restenosis after
      percutaneous coronary intervention and have been predicted to decrease the number
      of patients referred for coronary artery bypass grafting (CABG). The purpose of
      this study was to determine the impact of DES on the number and characteristics
      of patients referred for CABG. METHODS: Drug-eluting stents were introduced at
      our hospital in April 2003 and reached maturity by June 2003. We compared our
      isolated CABG patients from the 12 months before the introduction of DES (year 1)
      with those from the 12 months after full implementation of DES (year 2). RESULTS:
      In year 1, of 4,348 cardiac catheterization patients, 2,144 (49.3%) underwent
      percutaneous coronary intervention, and 432 (9.9%) had CABG. In year 2, of 3,986
      cardiac catheterization patients, 2,027 (50.9%) had percutaneous coronary
      intervention, and 337 (8.5%) had CABG, representing a 14% reduction in proportion
      of cardiac catheterization patients referred for CABG (p = 0.021). Among CABG
      patients, there was no change in age, prevalence of diabetes, or prevalence of
      three-vessel disease; however, patients in year 2 were more likely to have left
      main coronary artery disease (year 1, 36% versus year 2, 44.5%; p < 0.02) and
      left ventricular ejection fraction greater than 0.50 (year 1, 45% versus year 2,
      52%; p < 0.02). CONCLUSIONS: The clinical introduction of DES was associated with
      a modest decrease in the percentage of cardiac catheterization patients referred
      for CABG. Of those referred for surgery, an increasing proportion had left main
      coronary artery disease and preserved left ventricular systolic function.
      Defining the role of DES versus CABG for coronary revascularization will require
      elucidation of the long-term outcomes of DES compared with CABG.

PMID- 16564251
TI  - Total arterial revascularization is safe: multicenter ten-year analysis of 71,470
      coronary procedures.
AB  - BACKGROUND: The purpose of this study was to assess the use of arterial
      revascularization and to compare the in-hospital mortality with other CABG
      grafting strategies. METHODS: A total of 71,470 CABG patients (1992-2001) in 27
      centers in the United Kingdom were studied. The proportion of patients with
      arterial revascularization was compared. In-hospital mortality was compared for
      various grafting strategies: all-arterial (n = 5,401), all non-all-arterial
      patients (n = 66,069), one artery any number of veins (n = 49,801). The groups
      were compared for in-hospital mortality using multivariate logistic regression to
      assess the independent effect of the grafting strategies on mortality; logistic
      EuroSCORE-predicted mortality was compared to actual mortality, and all arterial
      and one artery and veins patients were compared with propensity score analysis.
      RESULTS: There was a significant increase in the proportion of all-arterial
      patients over time (3.2% to 11.7%, p < 0.001) with evidence of variability across
      centers. Crude mortality for all-arterial patients was 2% vs 3% for all non-all
      arterial patients (p < 0.001). In multivariate analysis, all-arterial was
      associated with a slight but insignificant increase in in-hospital mortality
      (odds ratio [OR] 1.13; [95% confidence interval {CI} 0.86-1.48], p = 0.36). There
      was a trend toward higher mortality in the all-arterial group when compared with
      the one artery and veins group (OR 1.19 [95% CI 0.91-1.56], p = 0.10). The one
      artery and veins group was the only group where actual mortality was
      significantly lower than predicted by EuroSCORE (p < 0.001). In propensity
      analysis the mortality was 1.51% for one artery and veins and 1.74% of all
      arterial patients (p = 0.56). CONCLUSIONS: The use of arterial grafting has
      increased over time, varies by center, and appears to be safe in terms of in
      hospital mortality.

PMID- 16564252
TI  - Follow-up of patients operated on with arterial patch angioplasty of the left
      main coronary artery.
AB  - BACKGROUND: Surgical angioplasty of the left main coronary artery (LMCA) can be
      performed with good results in selected patients. It restores the native
      antegrade blood flow in the LMCA and does not leave the patient with a graft
      dependent retrograde perfusion. By using a proximal segment of the right internal
      mammary artery as patch material, we assumed that this would minimize the risk of
      restenosis of the LMCA. We here review our experience and results. METHODS: Forty
      three patients were operated on with LMCA angioplasty from 1997 to 2003. Follow
      up at a mean of 45 months (range, 7 to 79) included a stress test,
      echocardiography, and angiography with intravascular ultrasound (IVUS) of the
      LMCA. RESULTS: There were three late deaths, none related to failure of the
      angioplasty. All patients included in the follow-up had preserved preoperative
      left ventricular function, and there was no aortic incompetence. The
      angioplasties investigated were patent, and no signs of restenosis or dilatation
      could be observed. The dimensions of the LMCA after angioplasty was in diameter
      4.8 mm (3.35 to 6.75 mm) and 5.6 mm (4 to 7.6 mm), and in area 18.9 mm2 (12.3 to
      31.9 mm2) and 24.8 mm2 (14.5 to 37 mm2) in the distal and proximal parts,
      respectively. CONCLUSIONS: Surgical angioplasty of the left main coronary artery
      using a proximal segment of the right internal mammary artery as an onlay patch
      is safe, with good long-term results.

PMID- 16564253
TI  - Invited commentary.

PMID- 16564254
TI  - Reduced cytokines release and myocardial damage in coronary artery bypass
      patients due to L-arginine cardioplegia supplementation.
AB  - BACKGROUND: Recently, L-arginine has been added to cardioplegia to limit
      myocardial ischemic damage. The mechanism of action is related to the production
      of nitric oxide, with vasodilatation and reduction of endothelial dysfunction.
      Our prospective randomized study on coronary artery bypass patients investigates
      the effect of L-arginine on myocardial stress as expressed by myocardial
      cytokines release and myocardial ischemia in terms of troponin T concentration.
      METHODS: Coronary artery surgery patients were randomly assigned to receive 7.5 g
      L-arginine in 500 mL of cardioplegic solution (group A). Group B was used as
      control. Cold blood 4:1 anterograde and retrograde cardioplegia with warm
      induction was administered. Blood samples were collected from the retrograde
      coronary sinus catheter to determine interleukin-2 receptor, interleukin-6, and
      tumor necrosis factor levels. Serum samples at different time points were also
      analyzed to measure myocardial ischemia markers. Hemodynamic and
      echocardiographic evaluations were obtained perioperatively. RESULTS: Sixty-five
      patients were enrolled (group A, treated with L-arginine, n = 33; group B,
      control, n = 32). Wedge pressure and intensive care unit stay were significantly
      reduced in group A (p = 0.023 and p = 0.03, respectively). Cytokines levels were
      lower in group A, with a significance for interleukin-6 (p = 0.026); troponin T
      was reduced in treated patients (0.33 versus 0.57 ng/mL at 18 hours: p = 0.009).
      CONCLUSIONS: Coronary artery surgery patients benefit from L-arginine
      cardioplegia supplementation in terms of reduced inflammatory reaction,
      limitation of myocardial ischemia, and better hemodynamic performance. Moreover,
      a clinical advantage is evident in terms of a shorter intensive care unit stay in
      patients treated with L-arginine.

PMID- 16564255
TI  - Neutrophil adherence to activated saphenous vein and mammary endothelium after
      graft preparation.
AB  - BACKGROUND: Interaction of circulating leukocytes and vascular endothelium plays
      an important role in vasoconstriction, endothelial dysfunction, and vascular
      injury. Dilation procedures of grafts before coronary artery bypass graft surgery
      might lead to vascular injury and subsequent bypass graft disease. METHODS: We
      analyzed in vitro the adherence of fluorescence-labeled polymorphonuclear
      neutrophils (PMNs) to endothelium of human saphenous vein grafts or internal
      mammary artery grafts after stimulation with thrombin (0.5 to 2 U/mL) or dilating
      procedures. Furthermore, we investigated endothelial function of prepared grafts.
      RESULTS: Thrombin stimulation resulted in a dose-dependent increase of PMN
      adherence to the endothelium of saphenous vein and internal mammary artery, which
      was attenuated by the selectin-blocking carbohydrate fucoidin or anti-P-selectin
      monoclonal antibody. Mechanical dilation of saphenous vein or internal mammary
      artery led to a marked increase in PMN adherence (65 +/- 5 versus 5 +/- 3
      PMN/mm2; p < 0.01), which was significantly attenuated by fucoidin or anti-P
      selectin monoclonal antibodies. Treatment of internal mammary artery with the
      vasodilator papaverine led to a marked increase of PMN adherence (59 +/- 8 versus
      12 +/- 4 PMN/mm2; p < 0.01) when papaverine was administered directly into the
      vessel. However, external treatment with papaverine did not affect PMN adhesion.
      Endothelial dysfunction was observed in dilated venous grafts and in arterial
      grafts internally treated with papaverine; in contrast, external treatment did
      not affect endothelial function. CONCLUSIONS: This study showed that mechanical
      or pharmacologic dilation of venous or arterial coronary grafts, usually
      performed before anastomosis of aortocoronary bypass grafts, led to increased
      selectin-mediated PMN adhesion on vascular endothelium and subsequent endothelial
      dysfunction.

PMID- 16564256
TI  - Selection of saphenous vein conduit in varicose vein disease.
AB  - BACKGROUND: Limbs with varicose veins are difficult to assess as a source of
      saphenous vein conduit. Anatomic, histologic, and ultrasound studies demonstrate
      two types of longitudinal veins in the lower extremities. The great saphenous
      vein is deep to the saphenous fascia. Accessory saphenous veins are superficial
      to this layer and have thin walls with diminished muscle cells and elastic fiber.
      Accessory saphenous veins dilate and form varicosities. Segments of great
      saphenous veins are often suitable as coronary conduits. No studies have assessed
      the suitability of saphenous veins as coronary artery conduits in patients with
      varicose vein disease. METHODS: Intraoperative high-resolution ultrasound studies
      were performed in coronary artery bypass graft procedures to assess lower
      extremity venous morphology in limbs of 77 patients without known venous disease,
      in 19 limbs with venous telangiectases, and in 23 limbs with varicose veins.
      RESULTS: Dilated great saphenous vein segments were identified in 6% of normal
      limb venous segments compared with 21% of segments in limbs with telangiectases
      (p = 0.027) and 22% of segments in limbs with varicosities (p = 0.012). The
      incidence of absent or hypoplastic great saphenous vein segments is increased in
      limbs with varicosities (35%) compared with normal limbs (21%; p = 0.032). In the
      calf, at least one great saphenous vein segment suitable for coronary artery
      bypass grafting is present in 70% of limbs with varicosities and in 89% of limbs
      with telangiectases. CONCLUSIONS: Ultrasound studies document that varicose veins
      are limited to accessory saphenous veins. Great saphenous vein conduits,
      identified by ultrasonography, are available in limbs with varicose vein disease.

PMID- 16564257
TI  - Management of central coronary sinus ruptures using the pericardial patch repair
      technique.
AB  - BACKGROUND: Intraoperative coronary sinus rupture is a rare event; however, it
      carries potential mortality and its' management is technically challenging. A
      repair technique should provide adequate bleeding control while avoiding
      narrowing or stricture of the coronary sinus. METHODS: We retrospectively review
      our experience with a new pericardial patch repair technique. From January 1996
      to May 2005 four cases of intraoperative coronary sinus injury were identified.
      Three female patients and one male patient with a mean age of 74 +/- 4 years
      underwent valve replacement and/or coronary artery bypass on cardiopulmonary
      bypass. A double pericardial patch technique sandwiched with human fibrin glue
      was used to cover the defect. RESULTS: In all patients treated with this method,
      the injury could be treated successfully. All patients were extubated on the
      first postoperative day and median intensive care unit stay was 3 days. Drains
      could be removed after 4 days median. Median hospital stay was 13 days. After a
      median follow-up of 33 months all patients are alive without any
      echocardiographic signs of impairments of the coronary sinus. CONCLUSIONS: We
      conclude that the pericardial patch technique is a safe and technically feasible
      technique for repair of central coronary sinus ruptures. Excellent bleeding
      control and, in our experience, no consecutive complications were observed.

PMID- 16564258
TI  - Repeat valvular operations: bench optimization of conventional surgery.
AB  - BACKGROUND: Repeat heart valve operations have become a quite common procedure.
      We reviewed our experience with reoperative valvular surgery during a 6-year
      period to assess the risk factors affecting in-hospital mortality and medium-term
      survival. METHODS: A series of 316 redo procedures performed on a total of 290
      patients in the period between 1997 and 2002 at our institution was
      retrospectively analyzed. Univariate and multivariable analyses were performed.
      RESULTS: In-hospital mortality was 3.8%; overall mortality at the end of a 30
      month follow-up was 9.3%. We identified advanced New York Heart Association
      class, advanced age, depressed ejection fraction, emergent or urgent
      presentation, impairment of renal function, and involvement of tricuspid valve as
      predictors of mortality. In contrast, duration of cardiopulmonary bypass and
      multiple valve procedure were not associated with increased short-term risk.
      CONCLUSIONS: The present study is characterized by particular attention in
      reducing confounding variables and biases correlated to heterogeneities. The main
      determinants of mortality are related to the degree of patients' illness rather
      than to inherent technical factors of reoperations. Although highest-risk
      individuals (previous coronary artery bypass grafting or coexistence of aortic
      aneurysm) were excluded from the study, our data suggest that patients undergoing
      isolated redo valvular procedures now face operative risks that are comparable to
      primary intervention.

PMID- 16564259
TI  - Risk factors of prosthetic valve endocarditis: a case-control study.
AB  - BACKGROUND: Prosthetic valve endocarditis is an important cause of the morbidity
      and mortality associated with heart valve replacement surgery. The objective of
      this study was to assess risk factors of prosthetic valve endocarditis related to
      patients, perioperative events, and postoperative complications. METHODS: This
      was a retrospective case-control study conducted in a tertiary care hospital in
      Santander, Spain, from January 1986 to January 1998. Cases were patients with
      "definite" and "possible" infective endocarditis defined according to the Durack
      criteria. Controls were patients undergoing prosthetic valve replacement who at
      the time of the study had not developed infective endocarditis. Information was
      abstracted from medical records. Cases and controls (1:2) were matched by sex,
      age at operation (+/- 5 years), surgery of one or more valves in the same
      anatomic position, and date of operation (+/- 6 months). RESULTS: There were 81
      cases and 162 controls. In the multivariate analysis, risk factors significantly
      associated with prosthetic valve endocarditis were functional class III or IV
      (New York Heart Association), alcohol consumption, prior history of endocarditis,
      fever in the intensive care unit, and gastrointestinal bleeding. Functional class
      III or IV and complications of the surgical wound were independent predictors of
      early infective endocarditis, whereas fever in the intensive care unit and
      gastrointestinal bleeding were predictors of prosthetic valve endocarditis late
      after operation. CONCLUSIONS: Patients with prosthetic valve endocarditis differ
      from people without infective endocarditis with regard to intrinsic and
      postoperative risk factors but not regarding perioperative-related variables.

PMID- 16564260
TI  - Hemolysis in mechanical bileaflet prostheses: experience with the Bicarbon valve.
AB  - BACKGROUND: Normal functioning mechanical heart valve prostheses are designed to
      have a certain degree of intrinsic structural regurgitation as a washout
      mechanism to avoid prosthetic thrombosis. However, intrinsic regurgitation leads
      to blood cell trauma and hemolysis. Information on hemolysis associated with
      mechanical bileaflet prostheses is scarce. This study evaluated factors
      influencing hemolysis in 197 Bicarbon mechanical bileaflet prostheses implanted
      in 164 patients. METHODS: Serial office interviews, laboratory studies, and
      echocardiography evaluations were done in the surviving patients. An assay for
      measuring lactate dehydrogenase activity was developed, and the presence and
      severity of subclinical hemolysis was determined using reported criteria and
      analyzed at 1 and 2 years. RESULTS: Hospital mortality was 5.5%. Follow-up was
      98.1% complete. No patient had clinically significant or severe subclinical
      hemolysis. Serum lactate dehydrogenase levels were significantly higher when a
      paravalvular leak was documented (282 +/- 85 U/L versus 242 +/- 64 U/L; p =
      0.0026). Subclinical hemolysis was significantly more frequent after mitral valve
      (p = 0.001) and double valve replacement (p = 0.001) than after aortic valve
      replacement, and was unrelated to prosthetic size or to geometric area index,
      even in those cases with effective orifice area index equal to or less than 0.85
      cm2/m2 (p = 0.298). CONCLUSIONS: Mild subclinical hemolysis is frequently
      associated with normal functioning Bicarbon heart valves. Subclinical hemolysis
      was significantly influenced by valve position but not by valve size or effective
      orifice area index and remained stable through time. The magnitude of hemolysis
      in Bicarbon prostheses compared favorably with that reported for other bileaflet
      heart valve prostheses.

PMID- 16564261
TI  - Risk factors for postoperative heart failure in patients operated on for aortic
      stenosis.
AB  - BACKGROUND: Risk factors for postoperative heart failure (PHF) have not been
      specifically studied in valve surgery although it has been acknowledged that
      patient variables may have a more profound influence on postoperative outcome
      than valve-related factors. METHODS: All patients undergoing isolated aortic
      valve replacement for aortic stenosis from January 1995 to December 2000 in the
      southeast region of Sweden were studied (n = 398). Forty-five patients with
      aortic valve replacement required treatment for PHF. Univariate and multivariate
      logistic regression analysis was carried out to identify risk factors for PHF.
      RESULTS: Thirty-day mortality was 6.7% versus 1.4% for patients with and without
      PHF, respectively (p = 0.05). With regard to clinical presentation of aortic
      stenosis, angina was associated with reduced risk, whereas history of congestive
      heart failure increased the risk for PHF. Five preoperative (hypertension,
      history of congestive heart failure, severe systolic left ventricular
      dysfunction, pulmonary hypertension, preoperative hemodynamic instability) and
      two intraoperative (aortic cross-clamp time, intraoperative myocardial
      infarction) variables were identified as independent risk factors for PHF.
      Patient-prosthesis mismatch did not influence the risk of PHF significantly.
      CONCLUSIONS: Postoperative heart failure was associated with a marked increase in
      postoperative mortality and morbidity. Risk factors for PHF were variables
      indicating preexisting myocardial dysfunction, increased right or left
      ventricular afterload, and intraoperative myocardial injury. Our results
      highlight issues concerning cross-clamp time and myocardial protection,
      particularly for patients with preoperatively compromised myocardial function.
      Asymptomatic patients with significant aortic stenosis should be considered for
      surgery before substantial echocardiographic evidence of left ventricular
      dysfunction or increased pulmonary artery pressure develops.

PMID- 16564262
TI  - Prevalence and avoidance of patient-prosthesis mismatch in aortic valve
      replacement in small adults.
AB  - BACKGROUND: It is still controversial as to whether a small prosthesis should be
      inserted or a small aortic annulus should be enlarged to minimize patient
      prosthesis mismatch (PPM). This retrospective study reviewed our strategy for
      avoiding PPM. METHODS: Isolated or combined aortic valve replacement was
      performed in 181 patients, including 24 patients (13.3%) aged less than 65 years
      with a small aortic annulus (< or = 21 mm) who underwent enlargement of the
      annulus by the Manouguian (n = 18) or Nicks (n = 6) procedure. In patients aged
      65 years or more, a Carpentier-Edwards Perimount pericardial (CEP) valve was
      implanted with few exceptions. We assessed our strategy for avoiding PPM by
      comparison with published normal reference values for the indexed effective
      orifice area. RESULTS: A CEP valve was implanted in 53 patients, and St. Jude
      Medical (SJM) mechanical valves were used in 128 patients. A standard 21-mm SJM
      valve was only used in 4 patients and no 19-mm valves were employed. However, 19
      mm CEP valves were used in 12 older patients with a small body surface area (1.43
      +/- 0.14 m2). No patient receiving an SJM valve had an indexed effective orifice
      area of 0.85 cm2/m2 or less, and PPM developed in only 2 (3.8%) of 53 patients
      receiving CEP valves. Consequently, the prevalence of PPM was 1.1%. The 10-year
      survival rates of patients receiving CEP or SJM valves with or without annular
      enlargement were similar. CONCLUSIONS: The prevalence of PPM was low in patients
      more than 65 years old with a relatively small body size who received
      bioprosthetic valves. In patients less than 65 years old with a small annulus,
      the method of first choice for avoiding PPM is aortic annular enlargement.

PMID- 16564263
TI  - Overreduction of the posterior annulus in surgical treatment of degenerative
      mitral regurgitation.
AB  - BACKGROUND: The concept of overreduction of the posterior annulus was applied in
      surgical treatment of degenerative mitral valve disease. METHODS: From April 1993
      to November 2004, 141 patients underwent overreduction of the posterior annulus
      of the mitral valve in mitral valve repair for degenerative disease. Mean scallop
      involvement per patient was 2.3 and increased to 3.0 in the last period.
      Correction of the prolapse of the posterior leaflet included resection with focal
      sliding (n = 100), or application of artificial chordae (n = 28), with (n = 11)
      or without (n = 17) plication of one or more scallops. The anterior leaflet
      prolapse was corrected with edge-to-edge technique (n = 20) or chordal
      replacement (n = 28). An overreducting ring, 40 (n = 81) or 50 (n = 60) mm long
      (autologous pericardium in 64 cases and Sovering Miniband [Sorin, Saluggia,
      Italy] in 77) was used in all the patients. RESULTS: Three patients died in the
      early period (2.1%) and 3 (2.1%) were reoperated on from 3 to 24 months due to
      endocarditis (2 cases) and failure of repair (1 case). Ten-year freedom from
      death any cause was 91.6%, from reoperation 96.4%, from death any cause and
      reoperation 87.7%, from death any cause, reoperation, and New York Heart
      Association class III-IV 79.8%. Sixty-four patients out of 68 who survived more
      than 2 years (94.1%) at a mean follow up of 4.2 +/- 2.5 years had no or 1+
      residual mitral regurgitation. CONCLUSIONS: Although the complexity of mitral
      valve repair for degenerative disease increased, results of surgery remained
      stable. Apposition of a posterior overreductive ring was useful to cover any
      mistake performed during the correction.

PMID- 16564264
TI  - Long-term clinical results of tricuspid valve replacement.
AB  - BACKGROUND: Tricuspid valve replacement (TVR) has been performed with mechanical
      or bioprosthetic valves. However, the relative advantages of the two types are
      incompletely known. METHODS: Between 1978 and 2003, we performed 138 TVR (35
      bioprosthetic, 103 mechanical) in 125 patients (50 men, 75 women), with a mean
      age of 43.7 +/- 16.6 years. The diseases that required TVR were rheumatic (94),
      prosthetic valve failure (14), congenital (14), infective endocarditis(5),
      isolated tricuspid regurgitation (4), and miscellaneous conditions (7). The
      operations included the following: isolated TVR (41), double valve replacement
      (58), and triple valve replacement (39). The follow-up rate was 98.3%, and
      cumulative follow-up was 828.5 patient-years. RESULTS: There were 22 in-hospital
      deaths (17.6%) and 13 (10.4%) late deaths. Fourteen patients required additional
      operations. There were 33 postoperative valve-related events including 11
      thromboembolisms and 3 bleeding episodes. Kaplan-Meier survival for the entire
      group at 15 years was 73.8 +/- 8.5% (bioprosthetic: 70.2 +/- 10.4%, mechanical:
      66.0 +/- 19.4%). At 15 years, freedom from reoperation was 66.3 +/- 9.4%
      (bioprosthetic: 55.1 +/- 13.8%, mechanical: 86.0 +/- 6.2%) and freedom from valve
      related events was 49.9 +/- 8.0%. The linearized incidence of valve thrombosis
      was 1.28%/patient-year (bioprosthetic: 0, mechanical: 1.92), anticoagulation
      related bleeding was 0.37%/patient-year (mechanical: 0.54), reoperation was
      1.71%/patient-year (bioprosthetic: 2.68, mechanical: 1.25), and valve-related
      events were 4.33%/patient-year (bioprosthetic: 3.83, mechanical: 4.6).
      CONCLUSIONS: Both bioprosthetic and mechanical valves revealed similar long-term
      outcomes. However, findings suggest that greater care is needed to prevent valve
      thrombosis in mechanical valves in the early postoperative period, and there is a
      greater chance for reoperation in bioprosthetic valves.

PMID- 16564265
TI  - Totally endoscopic ablation of lone atrial fibrillation: initial clinical
      experience.
AB  - BACKGROUND: Atrial fibrillation is the most common form of arrhythmia leading to
      hospital admission. Over 2.2 million Americans are affected by atrial
      fibrillation and approximately 160,000 new cases are identified annually. As the
      population continues to age, the number of patients will increase. AF is an
      incremental risk factor for death and stroke, and consumes billions of dollars in
      health care expenditures. METHODS: Between August 2003 and October 2004, 50 drug
      resistant, symptomatic atrial fibrillation patients underwent thoracoscopic or
      robotic-assisted off-pump epicardial microwave ablation with the FLEX 10 device
      (Guidant, Indianapolis, IN). There were 35 men (70.0%) and 15 women (30.0%), mean
      age 59.1 years +/- 10.0 (range, 37-75 years). Mean duration of atrial
      fibrillation was 73.5 months +/- 82.3 (range, 5-480 months). Thirty-three
      patients (66.0%) had intermittent atrial fibrillation and 17 (34.0%) continuous.
      Intermittent patients had pulmonary vein isolation whereas continuous patients
      had additional right and left atrial lesions performed. Forty-six patients
      (92.0%) had endoscopic stapling of the left atrial appendage. RESULTS: There were
      no hospital deaths. Postoperative in-hospital complications were minimal with 2
      patients (4.0%) experiencing diaphragmatic dysfunction. No patient required a
      permanent pacemaker implant. Mean postoperative length of stay was 3.7 +/- 2.2
      days. Cumulative follow-up was 335.8 patient months, mean 7.6 months (range, 2.0
      15.9 months). There was 1 late death (2.0%). In 5 patients (10.0%) the MicroMaze
      operation and subsequent electrophysiology intervention failed and a Cox-Maze III
      operation was performed. Follow-up was 100% complete with 79.5% (35 of 44)
      patients in normal sinus rhythm. CONCLUSIONS: Totally endoscopic closed-chest
      microwave ablation for treatment of intermittent and continuous atrial
      fibrillation is technically feasible and presents minimal risk to the patient.
      Initial results are impressive and demonstrate an enhanced quality of life and
      freedom from atrial fibrillation in drug-resistant symptomatic patients.

PMID- 16564266
TI  - Combined off-pump coronary artery bypass grafting surgery and ablative therapy
      for atrial fibrillation: early and mid-term results.
AB  - BACKGROUND: The aim of this study was to evaluate the feasibility of off-pump
      coronary artery bypass grafting combined with radiofrequency ablation and to
      compare outcomes between patients with permanent and paroxysmal atrial
      fibrillation (AF) in terms of restoring sinus rhythm. METHODS: Thirty-three
      patients underwent the combined procedure. Mean age was 62.34 +/- 8.20 years;
      there were 12 female and 21 male patients. Twenty-one patients were diagnosed as
      permanent AF (group A) and 12 had paroxysmal AF (group B). After the off-pump
      revascularization patients underwent pulmonary vein ablation. Rhythm was
      evaluated at discharge and at 6 and 12 months' follow-up. Patients in stable
      sinus rhythm underwent transthoracic echocardiographic examination to evaluate
      atrial contractility at 6 and 12 months. RESULTS: There was no operative
      mortality or major complications. The mean ablation time was 11 +/- 3.4 minutes,
      including multiple applications. At the end of the procedure 84.5% of patients
      were free of AF. Sinus rhythm was established in 56% (group A, 52%; group B,
      58.3%), 70.5% (group A, 58%; group B, 83.3%), and 71% (group A, 59%; group B,
      83.3%) of patients at discharge and at 6 and 12 months, respectively (p = 0.249).
      Biatrial contractility was detected in 71% of group A and 76% of group B patients
      at 6 months' follow-up. More patients in group A returned to AF during follow-up
      when compared with group B (p = 0.016). Female sex (odds ratio, 2.1), chronic
      lung disease (odds ratio, 1.40), left ventricular disfunction (p = 0.016), and
      hypertension (odds ratio, 2.57) emerged as risk factors for AF recurrence after
      ablation. CONCLUSIONS: Concomitant off-pump coronary artery bypass grafting and
      bipolar radiofrequency ablation was safe and effective. These patients should be
      considered for adjunctive treatment at the time of off-pump revascularization.

PMID- 16564267
TI  - Invited commentary.

PMID- 16564268
TI  - Critical evaluation of chest computed tomography scans for blunt descending
      thoracic aortic injury.
AB  - BACKGROUND: Although aortography has been the long-held "gold standard" for
      diagnosis of traumatic blunt aortic injury, advances in imaging technology offer
      less-invasive, more-rapid, and potentially more cost-effective evaluation. The
      purpose of this study was to review this hospital's experience with the screening
      and diagnosis of blunt aortic injury with emphasis on the critical evaluation of
      computed tomography (CT) scans for defining descending thoracic aortic injury.
      METHODS: A retrospective single-center analysis of all patients undergoing
      aortography to evaluate for blunt aortic injury between January 1, 1997, and
      August 31, 2004, was performed. A policy of relying on CT scans to definitively
      diagnose blunt aortic injury was not in force, and all patients with positive,
      equivocal, and negative screening CT scans with significant injury mechanism
      underwent subsequent aortography; this contributed to an unbiased analysis. A
      subgroup of patients imaged with the latest generation multislice CT scanners
      (July 1, 2003, to August 31, 2004) was separately analyzed with rapid three
      dimensional reconstruction. RESULTS: Of 856 aortograms, 206 (24.1%) were preceded
      by chest CT scan. Of 31 patients with confirmed aortic injury, 20 had undergone
      CT scan with 16 positive for definite injury, 3 positive for possible injury, and
      1 false-negative study. Of the 206 patients scanned, 114 (55.3%) showed possible
      injury, 76 (36.9%) were negative, and 16 (7.8%) were positive. Only 3 of the 114
      with possible injury (2.6%) were true positives whereas 1 of the 76 negative
      scans (1.3%) was a false negative and all 16 positive scans were true positives.
      These data for CT scan imaging result in a sensitivity of 95%, a specificity of
      40%, a positive predictive value of 15%, and a negative predictive value of 99%.
      CONCLUSIONS: Chest CT is an acceptable screening tool based on prerequisite high
      sensitivity and ease of performance in the trauma patient suspected of having a
      descending thoracic aortic injury. Although the excellent negative predictive
      value resulted in an algorithm change at this institution, there were a
      significant number of equivocal scans that required subsequent aortography. Three
      dimensional software reconstruction of the aorta can aid in diagnosing blunt
      aortic injury when findings are equivocal, but there will continue to be
      artifacts and limitations that require aortography for clarification.

PMID- 16564269
TI  - Invited commentary.

PMID- 16564270
TI  - Coma might not preclude emergency operation in acute aortic dissection.
AB  - BACKGROUND: Syncope or new onset focal neurologic deficits are described in as
      many as one fifth of patients with acute aortic dissection referred for surgery.
      Coma or stroke caused by involvement of the arch vessels and secondary brain
      malperfusion is considered a major contraindication for emergency aortic repair.
      Initial experience with emergency operation in selected patients with acute type
      A aortic dissection complicated by coma is described. METHODS: Five comatose
      (median Glasgow coma score, 5.5), hemodynamically stable (systolic blood pressure
      > or = 100 mm Hg) patients with preserved pupillary reactivity and coma duration
      of less than 12 hours underwent emergency surgical repair. The ascending aorta
      was always replaced using profound hypothermic circulatory arrest. RESULTS: There
      were no operative deaths. No hemorrhagic brain infarction developed
      postoperatively. Ischemic strokes were documented by radiology in 3 patients, and
      were always right-sided. Four patients returned to normal life with no neurologic
      sequelae, whereas 1 patient showed partially recovered left hemiparesis and mild
      cognitive impairment. CONCLUSIONS: Coma may not represent an absolute
      contraindication for resuscitative surgery in hemodynamically stable patients
      with acute type A aortic dissection. A larger experience is necessary to draw
      more definitive conclusions.

PMID- 16564271
TI  - Invited commentary.

PMID- 16564272
TI  - Surgical management of distal arch aneurysm: another approach with improved
      results.
AB  - BACKGROUND: Surgical treatment for distal arch aneurysm carries the risk of
      stroke. Although left thoracotomy has been used for repair of distal arch
      aneurysm as a standard approach, we have performed total arch replacement under
      deep hypothermia with circulatory arrest through a midsternotomy for this subset
      of aneurysms. METHODS: From January 1998 to February 2003, 119 patients underwent
      elective total arch replacement (mean age, 72.3 +/- 6.0 years) for distal arch
      aneurysm under deep hypothermia with circulatory arrest. Antegrade selective
      cerebral perfusion was used for brain protection. Arch vessels were independently
      reconstructed using quadrifurcated grafts. Concomitant procedures included
      tricuspid annuloplasty in 1 patient, aortic valve operations in 2, sinotubular
      junction plication in 6, and coronary artery grafting in 22. RESULTS: The early
      mortality rate was 0.84% (1 of 119). The mean duration of circulatory arrest was
      67.1 +/- 19.7 minutes. Perioperative stroke rate was 0.84% (1 of 119). This
      stroke occurred 9 days postoperatively in an 81-year-old man with a history of
      cerebral infarction. Other complications were reexploration for bleeding in 1
      patient (0.84%) and respiratory failure in 6 (5.0%). CONCLUSIONS: This operative
      approach for distal arch aneurysm featured a low mortality rate and low risk of
      perioperative stroke. Concomitant cardiac surgery could be performed routinely in
      standard fashion. Distal arch aneurysms that do not involve a large segment of
      the descending thoracic aorta can thus be repaired with low mortality and few
      cerebral complications through a midsternotomy.

PMID- 16564273
TI  - Aortic arch surgery: thoracoabdominal perfusion during antegrade cerebral
      perfusion may reduce postoperative morbidity.
AB  - BACKGROUND: This study aimed to assess the results of the introduction of
      thoracoabdominal perfusion (TAP) in the surgical strategy for aortic arch
      replacement with cerebral protection. METHODS: Two hundred two arch procedures
      performed with moderate hypothermia (22 degrees to 26 degrees C) and antegrade
      cerebral perfusion (ACP) were the objects of retrospective investigation. Acute
      type A dissection was the indication in 164 patients, aortic aneurysm in 38. In
      80 patients, during ACP, the thoracoabdominal aorta was perfused either in an
      antegrade fashion through proximal descending aorta endoluminal cannulation (in
      62 dissections), or retrograde through femoral artery cannulation with proximal
      descending aorta endoluminal occlusion (in 18 aneurysms). Hospital mortality and
      morbidity rates were compared between the two treatments (group A: ACP only, 122
      patients; group B: ACP plus TAP, 80 patients) and the underlying aortic disease
      (dissection/aneurysm) was stratified. RESULTS: Cerebral perfusion (p = 0.008) and
      cardiopulmonary bypass times (p = 0.035) were significantly longer in group B. No
      complication related to the TAP technique was observed in group B. Overall
      hospital mortality was 12.9%, without significant difference between groups. No
      differences were found in terms of permanent neurological dysfunction between
      groups A (9.3%) and B (9.1%; p = 0.58). Group B patients showed lower rates of
      respiratory failure (18.2% versus 30.5% in group A; p = 0.038), shorter
      mechanical ventilation times (18.1 +/- 26 hours versus 57.9 +/- 70.1; p < 0.001)
      and lower incidence of acute renal failure (6.5% versus 18.6%; p = 0.012).
      Shorter intensive care and hospital stays were observed in group B (p = 0.02).
      CONCLUSIONS: The adjunction of TAP to ACP was associated with lower rates of end
      organ complications, even in more extensive and time-consuming procedures.

PMID- 16564274
TI  - Safety and efficacy of left ventricular assist device support in postmyocardial
      infarction cardiogenic shock.
AB  - BACKGROUND: Cardiogenic shock secondary to acute myocardial infarction (CS-AMI)
      is the leading cause of death in all acute coronary syndromes. Experience with
      the use of left ventricular assist devices (LVADs) in patients with CS-AMI is
      limited. One of the surgical dilemmas when implanting an LVAD into a patient with
      an acute anterior wall myocardial infarction is the safety of apical cannulation.
      We present a decade of experience with the use of LVAD with apical cannulation in
      patients with CS-AMI. METHODS: A retrospective review of the ventricular assist
      device (VAD) database at the Hospital of the University of Pennsylvania was
      instituted. RESULTS: From April 1995 to February 2005, 49 patients received LVAD
      support for CS-AMI (group I). The majority of these patients suffered anterior
      wall myocardial infarctions. This group of patients was compared with a separate
      cohort of 61 patients with chronic ischemic cardiomyopathy who received LVAD
      support (group II). The VAD support successfully bridged 38 (74%) group I
      patients and 37 (61%) group II patients to heart transplantation. Of the 38
      patients transplanted in group I, 33 (87%) were discharged from the hospital. In
      group II, 36 of the 37 patients transplanted (97%) survived to hospital
      discharge. The overall in-hospital mortality rates for the series were 33% for
      group I patients, and 41% for group II patients. CONCLUSIONS: Left ventricular
      assist device support in patients with CS-AMI is a safe and effective therapy
      which should be incorporated into the standard treatment paradigm for appropriate
      patients presenting with this lethal disease.

PMID- 16564275
TI  - Expression of platelet-derived growth factor and fibroblast growth factor in
      cryopreserved endomyocardial biopsies early and late after heart transplant.
AB  - BACKGROUND: Growth factors such as platelet-derived growth factor (PDGF) and
      fibroblast growth factor (FGF) appear to play a key role in immunologic reactions
      in the long-term course after heart transplant. Their expression in the early
      phase after transplant has been recently described. The aim of the present study
      was, therefore, to examine the growth factor expression in the early and later
      periods, up to three years after transplant in the same patient cohort. METHODS:
      Right ventricular endomyocardial biopsies were obtained from 29 heart transplant
      recipients before implantation, after one and two weeks, and after one, two, and
      three years after heart transplant, and immediately frozen in liquid nitrogen.
      The growth factor expression was examined immunohistochemically. RESULTS: The
      PDGFs were mainly expressed in vascular structures and they were less pronounced
      in cardiomyocytes. Especially after the first week, a significant increase was
      found in the expression of PDGF A and B as well as PDGF-receptors alpha and beta.
      In the yearly biopsies, PDGF expression was rarely found. The bFGF expression was
      merely weak in the later period three years after transplant and the aFGF was
      only expressed in the early phase. A comparison of recipients with short and long
      ischemic time did not reveal any significant differences in the intensity of
      expression. CONCLUSIONS: The increased expression of PDGF and FGF in the first
      postoperative week can be interpreted as an unspecific reaction to peritransplant
      injury. This might be related to important reparative, angioprotective, and wound
      healing processes shortly after the heart transplant had taken place. The weak
      expression in the later period appears to be linked to a stable transplant
      function and a direct influence by the immunosuppressive therapy.

PMID- 16564276
TI  - Cardiac surgery in renal transplant recipients: experience from Washington
      Hospital Center.
AB  - BACKGROUND: The number of renal transplant survivors requiring surgical treatment
      for cardiovascular diseases is increasing. A retrospective study was conducted to
      determine the outcomes of renal transplant recipients undergoing cardiac surgery.
      METHODS: Fifty-seven renal transplant recipients whose cardiac surgery was
      performed between 1987 and 2004, and whose allograft was functioning at the time
      of cardiac surgery, were identified. We analyzed postoperative mortality and
      morbidity as well as late mortality. RESULTS: Among 57 patients, 70.2% had
      hypertension, 54.4% diabetes, and 28.1% poor left ventricular function (ejection
      fraction < 0.35). Preoperative renal insufficiency (serum creatinine level > or =
      3 mg/dL) was noted in 12.3% of the patients. Coronary artery disease was the
      dominant indication for the surgery. The median interval from renal transplant to
      cardiac surgery was 60 months. In-hospital mortality was 5.3%. All deaths were
      cardiac-related. Infectious complications occurred in 17.5% of the patients.
      Acute allograft failure requiring hemodialysis occurred in 28.6% of the patients
      with preoperative renal insufficiency, more frequent than those without
      preoperative renal insufficiency. Multivariable analysis identified preoperative
      renal insufficiency, mitral valve disease, and left ventricular dysfunction as
      independent predictors of in-hospital major adverse events (including death,
      infection, and renal failure). The 3-year survival was 71% after a median follow
      up of 34 months. CONCLUSIONS: Infection control and renal protection should be
      stressed to ensure the safety of cardiac surgery in this patient group, while
      preoperative renal insufficiency, mitral valve disease, and left ventricular
      dysfunction are associated with early adverse outcomes. In the renal transplant
      recipients undergoing an isolated CABG, avoidance of cardiopulmonary bypass and
      use of arterial grafts might lead to better outcomes.

PMID- 16564277
TI  - Predicting survival in patients requiring renal replacement therapy after cardiac
      surgery.
AB  - BACKGROUND: We sought to develop and internally validate a prediction score for
      all-cause in-hospital mortality in patients who have acute renal failure and
      require renal replacement therapy after cardiac surgery. METHODS: From January
      1992 to July 2001, 136 of 14,000 patients (0.9%) had acute renal failure
      requiring renal replacement therapy after cardiac surgery. Multivariate logistic
      regression analysis, based on pre-renal replacement therapy variables, was used
      to construct a predictive score for all causes of in-hospital mortality.
      Subsequently, the score was validated in 27 patients who underwent surgery
      between August 2001 and March 2003. RESULTS: In-hospital mortality was 58% (79 of
      136). From the logistic regression model, we assigned a score (range, 0 to 6)
      based on the presence of independent predictors of operative mortality
      (preoperative creatinine < or = 1.5 mg/dL [odds ratio (OR) = 5.0], hypertension
      [OR = 4.4], predialysis coma [OR = 9.6], sepsis [OR = 6.4], and total bilirubin >
      or = 2 mg/dL [OR = 5.6]). Higher scores strongly predicted mortality: patients
      who scored 3 or higher before the initiation dialysis (n = 54), had a mortality
      rate of 94% (51 of 54). In contrast, patients who scored 1 or less on this scale
      (n = 36), had a mortality of 16% (6 of 36). In the validation cohort, the
      sensitivity of the new score at the cutoff of 2 or fewer points versus 3 or more
      points was 0.71, the specificity was 0.90, the positive predictive value was
      0.92, and the negative predictive value was 0.64. CONCLUSIONS: The prediction
      score represents a simple and accurate tool for predicting in-hospital mortality
      associated with renal replacement therapy for cardiac surgery patients before the
      institution of this resource-intensive treatment.

PMID- 16564278
TI  - Comparison of three measurements of cardiac surgery mortality for the Northern
      New England Cardiovascular Disease Study Group.
AB  - BACKGROUND: There is no consensus on the optimal period during which to assess
      death after coronary artery bypass graft (CABG) surgery. Three measures are
      commonly used: in-hospital, 30-day, and procedural (either in-hospital or 30-day)
      mortality. We used a regional database to calculate the CABG mortality rate using
      each of these mortality measures. METHODS: Data were collected prospectively on
      31,592 consecutive isolated CABG surgeries in northern New England between
      January 1992 and December 2001. These data were linked to the National Death
      Index to obtain vital status through December 2001, and used to calculate 30-day
      and procedural mortality rates. Procedural mortality was defined as death
      occurring either within the hospital setting or within 30 days of the index
      procedure. Regional registry data were used to calculate in-hospital mortality
      rates. RESULTS: Mortality rates and their 95% confidence intervals were
      calculated. In all but one medical center, the in-hospital mortality was the
      lowest rate, while in all centers the procedural mortality rate was the highest.
      There were 1,082 deaths captured by the procedural mortality measure. Of these,
      927 were included in the in-hospital mortality measure; 956 occurred within 30
      days of surgery. CONCLUSIONS: Each of the measures studied has its advantages and
      may be used to assess the mortality outcomes of cardiac surgery. The more
      important issue other than the specific measure used is our ability to measure
      and validate it conveniently and accurately in actual practice.

PMID- 16564279
TI  - Mini-cardiopulmonary bypass system: results of a prospective randomized study.
AB  - BACKGROUND: We studied postoperative mortality and morbidity after coronary
      artery bypass graft surgery performed using the mini-extracorporeal circulation
      (MECC) system. METHODS: From June 2001 to June 2002, we randomly enrolled 60
      patients who underwent isolated elective coronary artery bypass graft surgery,
      and were operated on with the MECC system (30 patients: group A) or standard
      cardiopulmonary bypass (30 patients: group B). Serial blood samples were
      collected to evaluate the main preoperative, intraoperative, and postoperative
      clinical and biological variables; and to measure hemolysis, interleukin-6
      cytokine, and plasma C-reactive protein release. RESULTS: A more stable
      hemoglobin level was detected in group A. The platelet count did not show a
      significant difference between the two groups. Interleukin-6 cytokine release
      showed higher values in group B, although no difference between groups was
      statistically significant. The time course of circulating plasma C-reactive
      protein concentration exhibited the same increase in both groups. Plasma free
      hemoglobin levels showed higher hemolysis peaks in group B, although a
      statistical significant difference was detected only at 4 hours after surgery. A
      higher cardiac index and reduced systemic and pulmonary vascular resistance index
      in the early postoperative period were found in group A at postoperative time 30
      minutes. CONCLUSIONS: Our experience shows that MECC offers satisfactory clinical
      benefits in terms of good hemodynamic support, safety, and low morbidity,
      although the study failed to demonstrate a significant clear superiority of MECC
      versus conventional cardiopulmonary bypass. The results need to be confirmed by a
      larger prospective, randomized study comparing MECC and standard cardiopulmonary
      bypass.

PMID- 16564281
TI  - Invited commentary.

PMID- 16564280
TI  - Cerebral outcome in adult patients treated with extracorporeal membrane
      oxygenation.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) carries a high risk of
      brain injury. The aim of this study was to determine the cerebral status in 28
      adult survivors on average 5.0 (range, 0.5 to 12) years after ECMO treatment for
      severe cardiorespiratory failure. METHODS: All 28 patients were investigated at
      our institution. A comprehensive assessment protocol included a medical history,
      physical examination, neuropsychological assessment, electroencephalography, and
      neuroradiologic assessment. RESULTS: All patients were ambulant unaided, and 43%
      were without any clinical findings. Impaired neuropsychological performance was
      found in 41%, neuroradiologic findings in 52%, and a pathologic
      electroencephalogram in 41% of the patients. There was a significant correlation
      between the cognitive outcome and neuroradiologic findings. The incidence of
      neuroradiologic findings (cerebral infarction, microemboli or hemorrhage) was
      significantly higher in the venoarterial group compared with the venovenous group
      (75% versus 17%). There was no correlation between the type of ECMO and
      neuropsychological impairment. Electroencephalography findings did not correlate
      with neuropsychological performance, nor with the neuroradiologic findings.
      CONCLUSIONS: Late cerebral sequelae were frequently seen in patients treated on
      venoarterial ECMO. A significant correlation was found between cognitive
      impairment and neuroradiologic findings.

PMID- 16564282
TI  - Diazoxide provides maximal KATP channels independent protection if present
      throughout hypoxia.
AB  - BACKGROUND: It is not clear what the optimal timing of diazoxide administration
      for cardioprotection in human myocardium is. We aimed to establish it. We next
      checked whether protection depended on adenosine triphosphate (ATP)-inhibited
      potassium (KATP) channels. METHODS: Isolated human right atrial trabeculae were
      subjected to 90-minute hypoxia and 120-minute reoxygenation in vitro, followed by
      adding 10(-4) M norepinephrine. Diazoxide (100 microM) was added (1) as a 10
      minute preconditioning signal with 10-minute washout before hypoxia or (2) 10
      minute pretreatment without washout before hypoxia or (3) throughout hypoxia or
      (4) 10 minutes before and throughout hypoxia or (5) during the first 20 minutes
      of reoxygenation only. In the control, no diazoxide was added. In another set of
      experiments, diazoxide (100 microM) was present throughout hypoxia in control,
      while we tried to inhibit its protective effect with glibenclamide (1, 10, 100
      microM) or 5-hydroxydecanoate (100 microM). RESULTS: The presence of diazoxide
      throughout hypoxia improved recovery of contractility during reoxygenation,
      allowed for significant response to norepinephrine at the end of reoxygenation,
      prevented "ischemic contracture" development, and reduced release of troponin I
      to tissue bath during hypoxia. Adding diazoxide 10 minutes before hypoxia
      conferred significantly weaker protective effects in all the above respects. We
      failed to show a protective effect of diazoxide used as a preconditioning signal
      or during reoxygenation. Neither 5-hydroxydecanoate nor glibenclamide
      significantly influenced protective effects of diazoxide added during hypoxia.
      CONCLUSIONS: Administration of diazoxide throughout hypoxia provided maximal
      protective effect, suggesting that diazoxide may be an important adjunct to
      cardioplegic solution. The protection offered by diazoxide used during hypoxia
      appears independent of its influence on KATP channels.

PMID- 16564283
TI  - Invited commentary.

PMID- 16564284
TI  - New minimally invasive technique to occlude secundum atrial septal defect in 53
      patients.
AB  - BACKGROUND: Conventional surgical atrial septal defect (ASD) closure requires
      cardiopulmonary bypass, whereas percutaneous transcatheter closure is limited by
      maximal defect size of 34 mm and access to the neck. We describe a new minimally
      invasive approach using a right minithoracotomy to deploy an occluder without
      cardiopulmonary bypass. METHODS: Between October 2004 and April 2005, 53 secundum
      ASDs were closed by this method. Through a 3-cm incision in the right fourth
      intercostal space, a minithoracotomy exposes the right atrium to facilitate
      deployment of the septal closure device. The age of the patients was from 2 to 61
      years. The ASD size was 12 to 39 mm. RESULTS: All ASDs were successfully closed
      with a mean device size of 33.1 +/- 8 mm (range, 16 to 46 mm). The procedure
      duration was 30 to 60 minutes. All patients were extubated on table, with less
      than a 1-day stay in the intensive care unit. The hospital stay was 3 to 7 days.
      There was no postoperative mortality. At mean follow-up of 1 to 8 months, there
      were no major morbidities. One patient had minimal residual shunt that resolved 1
      month later. CONCLUSIONS: This new minimally invasive method of secundum ASD
      closure is safe and cosmetically superior to conventional surgery. Early results
      are encouraging.

PMID- 16564285
TI  - Subclavian flap repair: review of 399 patients at median follow-up of fourteen
      years.
AB  - BACKGROUND: Conflicting results have been obtained for the same operation for
      repair of coarctation of the aorta by different institutes. The purpose of this
      study was to assess the results of subclavian flap aortoplasty (SFA) alone,
      performed on 399 patients in a single institute between 1966 and 1995. METHODS:
      Data were collected retrospectively from the congenital cardiac surgical database
      at the institute. RESULTS: The median age at operation was 22 days (3 days-49
      months). One hundred thirty-four patients had isolated coarctation while 265
      children had complex coarctation. Maximum follow-up was 24 years (median, 14
      years). Overall mortality over the whole duration of follow-up was 24.8%.
      Mortality for isolated coarctation at first intervention was 7.4% (operative
      mortality, 2.6%) while it was 12.8% for complex coarctation. At second
      intervention the mortality for isolated coarctation was 5%. For the second,
      third, and fourth interventions the mortality for complex coarctation was 25%,
      25%, and 27%, respectively. The survival for isolated coarctation at 1, 5, 10,
      and 20 years was 94%, 93.2%, 92.4%, and 88.4%, respectively, while it was 74.6%,
      66.3%, 63%, and 61.4%, respectively, for complex coarctation. Of the total
      patients, 15.3% had interventions for recoarctation. The incidence of
      recoarctation was 13.6% on those patients operated on in the first month of life,
      while it was 3.6% in older children. A percentage of 3.3% of patients continue to
      be hypertensive and require medication. There was a significant difference
      between the systolic blood pressure and anthropometric measurements between the
      arms. Despite this none of the patients complained of effect on lifestyle.
      CONCLUSIONS: Despite improved early results the long-term mortality for
      coarctation remains high. Mortality is higher for complex coarctation as compared
      with isolated procedures. The incidence of recoarctation after SFA at long term
      is acceptable and is higher in patients operated on in the first month of life.
      The overall incidence of hypertension is quite low. Patients remained
      normotensive when operated upon at the age of 0.9 months. The SFA, no doubt,
      effects the limb development; however it does not cause limitation in the
      lifestyle.

PMID- 16564286
TI  - Invited commentary.

PMID- 16564288
TI  - Invited commentary.

PMID- 16564287
TI  - Inhaled nitric oxide use in bidirectional Glenn anastomosis for elevated Glenn
      pressures.
AB  - BACKGROUND: Children frequently undergo bidirectional Glenn anastomosis in the
      staged surgical management of single ventricle physiology. The purpose of our
      study was to investigate the role of inhaled nitric oxide therapy in children
      with marked elevations in Glenn pressures after this surgery. METHODS: A
      retrospective study over a 30-month period was performed. The effect of inhaled
      nitric oxide therapy was analyzed in children with marked elevations of Glenn
      pressures resulting in decreased systemic perfusion. Effects on Glenn pressures,
      respiratory indices, and systemic perfusion were evaluated after initiation of
      nitric oxide therapy and compared with baseline parameters. RESULTS: Sixteen
      patients were placed on nitric oxide therapy for marked elevations of Glenn
      pressures (22.4 +/- 3.9 mm Hg). In the 11 responsive patients, there were
      significant reductions in Glenn pressures (from 22.4 mm Hg to 17.1 mm Hg, p <
      0.001) and significant improvement in partial pressure of oxygen to fraction of
      inspired oxygen ratio (from 49 to 74.3, p = 0.001) and oxygenation index (from 17
      to 12, p = 0.005). There was simultaneous significant reduction in inotrope score
      (from 14.9 to 11.4, p < 0.001) and fluid volume support (from 11.4 mL/kg to 2.3
      mL/kg, p < 0.001) in the responsive patients. Five patients that failed to show
      any response were found, subsequently, to have an anatomic lesion. CONCLUSIONS:
      Inhaled nitric oxide produces significant reduction in Glenn pressures and
      improvement in systemic perfusion and pulmonary gas exchange in patients with
      marked elevations of Glenn pressures after bidirectional Glenn anastomosis.
      Patients who fail to respond should be investigated for an anatomic lesion.

PMID- 16564289
TI  - Noninvasive assessment of repaired tetralogy of Fallot by magnetic resonance
      imaging and dynamic radionuclide studies.
AB  - BACKGROUND: This study was designed to validate the diagnostic accuracy of
      magnetic resonance imaging (MRI) in evaluating biventricular ejection fraction
      and to quantify pulmonary regurgitant fraction (PRF) in patients after repair of
      tetralogy of Fallot. METHODS: Two hundred and eighty survivors of repaired
      tetralogy of Fallot aged 42 months to 40 years (mean, 142.2 +/- 85.3 months)
      underwent cardiac MRI, first-pass and gated radionuclide ventriculography (RNV)
      for the assessment of biventricular function, and PRF after 89.26 +/- 42.40
      months. The receiver operating characteristic curve analysis was done to quantify
      the diagnostic accuracy of MRI. RESULTS: There was statistically significant
      agreement between MRI and RNV in evaluating right and left ventricular function.
      An MRI-derived right ventricular ejection fraction 47.2% or greater than normal
      was associated with a sensitivity of 92.3% and a specificity of 92.3%. An MRI
      derived left ventricular ejection fraction 53.9% or greater than normal was
      associated with a sensitivity of 93.2% and a specificity of 93.3%. Area analysis
      indicated that 97.34% (standard error [SE] = 0.0118) and 98.56% (SE = 0.0052) of
      the time values of right and left ventricular ejection fraction were higher for
      patients with normal right and left ventricular functions, respectively, compared
      with abnormal. There was a strong agreement between velocity-encoded and stroke
      volume-derived PRF [(r = 0.886, p < 0.001; d = 2.62 +/- 1.12, p < 0.0001; r' =
      0.121, p = 0.051; b = 0.96 (SE = 0.012); p < 0.0001; ICC = 0.98, p < 0.0001).
      Higher PRF was associated with increased indexed right ventricular dimensions and
      inversely correlated with biventricular ejection fractions. CONCLUSIONS: The MRI
      derived ejection fraction values predictably separate patients with normal
      ventricular function from abnormal. Velocity-encoded MRI can accurately
      quantitate PRF in tetralogy of Fallot.

PMID- 16564290
TI  - Ventricular volumes in Ebstein's anomaly: x-ray multislice computed tomography
      before and after repair.
AB  - BACKGROUND: This study was performed to measure right and left ventricular
      volumes in Ebstein's anomaly before and after operation. METHODS: Twenty-six
      consecutive patients were operated on with tricuspid valve repair and plication
      of the atrialized right ventricle, associated with a bidirectional cavopulmonary
      shunt in 15 patients. Right ventricular (RV) and left ventricular end-diastolic
      and end-systolic volume indexes were measured by x-ray computerized tomography
      before and after surgical repair. Left ventricular stroke index and ejection
      fraction were calculated. RESULTS: Before surgery, the mean stroke index of the
      atrialized RV was 36 +/- 33 mL/m2, with severe reduction in 9 patients and
      aneurysmal aspect in 2 patients. After surgery, the atrialized RV was no longer
      identifiable. Both RV end-diastolic volume index and stroke index of the
      remaining effective RV were reduced. Bidirectional cavopulmonary shunt was a
      determinant factor of decrease in the effective RV end-diastolic volume index
      after repair. Conversely, left ventricular ejection fraction and stroke index
      increased significantly after surgery. CONCLUSIONS: The atrialized RV with
      dyskinesia seems a good indication for a plication. RV end-diastolic volume index
      of the effective RV decreased after surgery. In severe cases, bidirectional
      cavopulmonary shunt was useful by decreasing RV end-diastolic volume, thus
      preventing further RV dilation. In all cases left ventricular ejection fraction
      and stroke volume index increased after surgery.

PMID- 16564291
TI  - Utilization of double-orifice valve plasty in correction of atrioventricular
      septal defect.
AB  - BACKGROUND: Atrioventricular valve regurgitation represents the principal
      indication for reoperation after repair of atrioventricular septal defect.
      Deciding how to correct atrioventricular valve regurgitation is challenging in
      some cases because of the complexity of the anatomic features. This report deals
      with our surgical experience in using a double-orifice valve plasty technique in
      cases with atrioventricular septal defect. METHODS: From August 2002 to August
      2004, 8 patients underwent double-orifice valve plasty in surgical correction of
      atrioventricular septal defect. Anatomic types were partial (6 patients),
      intermediate (1 patient), and complete (1 patient). After the mitral cleft was
      closed, moderate to severe atrioventricular valve regurgitation was still present
      in these patients. Double-orifice valve plasty was used in the mitral valve in 7
      patients and in the tricuspid valve in 1. RESULTS: No hospital deaths or
      postoperative morbidity occurred. The follow-up ranged from 6 months to 30 months
      (median, 14.4 months). No or trivial atrioventricular valve regurgitation was
      found in 6 patients and mild atrioventricular valve regurgitation was present in
      2. CONCLUSIONS: Double-orifice valve plasty is an easy and effective additional
      procedure for children and for adult patients who have moderate or severe
      atrioventricular valve regurgitation after repair of atrioventricular septal
      defect.

PMID- 16564292
TI  - Phosphorylcholine coating of bypass systems used for young infants does not
      attenuate the inflammatory response.
AB  - BACKGROUND: Contact of blood with the artificial surfaces of the cardiopulmonary
      bypass (CPB) system is considered to be a main cause of complement activation.
      Improving the biocompatibility of the system by reduction of contact activation
      of blood elements and thereby producing less inflammatory response is evidently
      desired, especially for neonates and infants who are more susceptible to the
      deleterious effects of CPB. A phosphorylcholine coating, Phisio, is designed to
      mimic the natural interfaces of blood. The aim of this study is to compare the
      influence of a phosphorylcholine-coated CPB system versus an uncoated CPB system
      on complement activation and clinical outcomes. METHODS: In this prospective,
      randomized, blind, one-center study, 28 neonates and infants with a bodyweight
      between 3 and 6 kg who were undergoing cardiopulmonary bypass were divided in two
      groups, the phosphorylcholine group and the control group. Thirteen patients were
      assigned to the phosphorylcholine group and 15 patients to the control group.
      Patients with Down syndrome, prematurity, cyanosis, or reoperation were excluded.
      Complement factor C3b/c, human neutrophil elastase (HNE), interleukin-6, and C
      reactive protein were measured before, during, and after CPB. Duration of
      intensive care stay, ventilation time, highest body temperature, and inotropic
      medication were the clinical variables. RESULTS: No significant differences were
      found between the groups for complement factor C3b/c, HNE, interleukin-6, or C
      reactive protein during and after CPB. No clinical differences were observed
      between the groups. CONCLUSIONS: Phosphorylcholine coating does not attenuate the
      complement activation during CPB in neonates and infants.

PMID- 16564293
TI  - Pulmonary artery hypertension: is it really a contraindicating factor for early
      extubation in children after cardiac surgery?
AB  - BACKGROUND: One of the perceived major contraindications to early extubation
      after pediatric cardiac surgery is preoperative pulmonary arterial hypertension
      (PAH). The objective of this study is to present the results of early extubation
      (within 6 hours after open heart surgery) in children who had varying degrees of
      preoperative pulmonary arterial hypertension. METHODS: We reviewed the charts of
      100 consecutive children who underwent subaortic ventricular septal defect
      closure and also had preoperative PAH. Outcomes measured included early
      extubation rate, clinical status of patients, and hospital costs. RESULTS: The
      median age at surgery was 2.5 years (range, 0.4 to 30). Sixty-five patients were
      extubated successfully in the operating room; 25 additional patients were
      extubated in the intensive care unit within 6 hours from surgery, increasing the
      early extubation rate from 65% to 90%. Postoperative complications were present
      in 12 patients; 10 of these patients required mechanical ventilation for more
      than 6 hours, and 1 of them died postoperatively in septic shock. Two patients
      required reintubation 25 and 26 hours, respectively, after initial extubation in
      the operating room, for causes unrelated to pulmonary hypertensive crises or
      ventilatory failure. The mean cost of procedures in patients who had successful
      early extubation was USD 3,786.50 +/- 302.45. Every additional day in the
      intensive care unit, in case of delayed extubation, increased the overall cost of
      the procedure by 10%. CONCLUSIONS: Pulmonary artery hypertension does not seems
      to be a contraindicating factor to early extubation in patients who underwent
      ventricular septal defect closure, and may be considered a feasible way to
      decrease postoperative intensive care unit stay and hospital costs.

PMID- 16564294
TI  - Tissue engineering of viable pulmonary arteries for surgical correction of
      congenital heart defects.
AB  - BACKGROUND: Tissue-engineered pulmonary arteries could overcome the drawbacks of
      homografts or prosthetic conduits used in the repair of many congenital cardiac
      defects. However, the ideal scaffold material for tissue-engineered conduits is
      still subject of intensive debate. In this study, we evaluated an acellularized
      allogeneic matrix scaffold for pulmonary artery tissue engineering with and
      without in-vitro reseeding with autologous endothelial cells in the pulmonary
      circulation in a growing sheep model. METHODS: Ovine pulmonary arteries (n = 10)
      were acellularized by trypsin/ethylenediamine tetraacetic acid incubation.
      Autologous endothelial cells were harvested from carotid arteries, and the
      pulmonary conduits were seeded with endothelial cells. We implanted in-vitro,
      autologous, reendothelialized (group A, n = 5) and acellularized pulmonary
      conduits (group B, n = 5) in the pulmonary circulation. The animals were
      sacrificed 6 months after the operation. Explanted valves were examined
      histologically and by immunohistochemistry. RESULTS: The conduit diameter
      increased in both groups (group A, 44% +/- 11%; group B, 87% +/- 18%; p < 0.05).
      In group A, however, a proportional increase in diameter was present, whereas in
      group B, a disproportionate increase resulting in aneurysm formation was
      observed. Histologically, the conduit wall integrity was destroyed in group B and
      preserved in group A. In group B, the extracellularmatrix degenerated with a
      reduced amount of collagens and proteoglycanes. Furthermore, no elastic fibers
      were detectable. In contrast, the extracellularmatrix in group A was close to
      native ovine tissue. CONCLUSIONS: Tissue-engineered pulmonary conduits
      (autologous endothelial cells and allogeneic matrix scaffolds) functioned well in
      the pulmonary circulation. They demonstrated an increase in diameter and an
      extracellular matrix comparable to that of native ovine tissue.

PMID- 16564295
TI  - Successful endothelialization of porcine glutaraldehyde-fixed aortic valves in a
      heterotopic sheep model.
AB  - PURPOSE: The purpose of our study was to evaluate the stability of an
      artificially seeded endothelial cell layer on porcine aortic prostheses under in
      vivo conditions in the arterial system. DESCRIPTION: Ten female sheep were
      divided into two groups. Animals of the study group (n = 7) had dissection of
      their right external jugular vein for cell harvesting. Myofibroblasts and
      endothelial cells were labelled with PKH-26, seeded onto pretreated (10% citric
      acid) porcine glutaraldehyde-fixed aortic valves (Freestyle, Medtronic Inc,
      Duesseldorf, Germany), and the valves were implanted into the descending aorta.
      Controls (n = 3) received pretreated but unseeded valves. A shunt between the
      aortic arch and the left atrial appendage ensured systolic or diastolic leaflet
      motions, or both, that were documented by sonography. After 3 months the valves
      were explanted. Specimens for scanning electron microscopy and
      immunohistochemical staining were taken prior to implantation and after
      explantation. EVALUATION: A neointimal proliferation was detected in the control
      group. No endothelial cells were found on the leaflets and the sinuses, but
      erythrocytes and thrombocytes were seen entrapped within the collagen fibers.
      Thrombus formation was documented macroscopically and histologically on the
      leaflets and the sinuses. In the study group a confluent endothelial cell layer
      was documented on the walls and leaflets. Neither neointimal proliferation nor
      any clots were seen. Some cells were still labelled positively indicating their
      origin from the initial cell seeding. No dilatation of any prosthesis was
      observed, but all valves showed slight thickening of the leaflets. CONCLUSIONS:
      The artificially seeded endothelial cell layers remained stable under in vivo
      conditions in the arterial system. Biocompatibility of the prostheses seemed to
      be improved by reduction of thrombogenicity.

PMID- 16564296
TI  - Tracheobronchopathia osteoplastica: cause of difficult tracheal intubation.
AB  - Tracheobronchopathia osteochondroplastica is a rare benign disorder affecting the
      trachea and the bronchi. We report a case presenting as difficulty during
      tracheal intubation. Chest roentgenogram revealed nothing before surgery.
      Findings on computed tomographic imaging scans show calcified nodular densities
      protruding into the tracheal lumen, with an abnormally irregular tracheal
      morphology and decreased lateral diameter. The fiber optic bronchoscopy, which
      was unable to pass more than 4 to 5 cm, showed enormous prominent protrusion with
      significant narrowing of the tracheal lumen. The diagnosis was confirmed by
      virtual bronchoscopy, which showed a tracheal narrowing with a beaded appearance
      and an irregular border that extended into the trachea and main bronchi.

PMID- 16564297
TI  - Management of multiple tension pneumatoceles refractory to tube thoracostomy
      decompression.
AB  - A 10-month-old boy had multiple tension pneumatoceles develop 4 weeks after
      pneumonia with parapneumonic empyema caused by methicillin-resistant
      Staphylococcus aureus. The pneumatoceles failed to completely respond to tube
      thoracostomy drainage, and sudden onset of cardiopulmonary collapse occurred
      after induction of anesthesia. He was rescued by multiple percutaneous venous
      catheter decompressions, followed by lobectomy. Our experience showed that
      surgery remains the definitive treatment for pediatric patients with multiple
      tension pneumatoceles. However, extra caution should be taken in the preoperative
      management of these patients, even in the presence of tube thoracostomy.

PMID- 16564298
TI  - Traumatic hemoptysis treated with recombinant human factor VIIa.
AB  - Blunt thoracic trauma resulting in massive hemoptysis is rare. Although there are
      several indications for the administration of recombinant factor VIIa, we are
      unaware of a report of its utilization in the treatment of hemoptysis following
      chest trauma. We report a case of the successful use of factor VIIa in the
      treatment of life-threatening hemoptysis secondary to blunt force thoracic injury
      and traumatic coagulopathy.

PMID- 16564299
TI  - Extraskeletal Ewing's sarcoma presenting with multifocal intrathoracic mass
      lesions associated with mediastinal shift.
AB  - Extraskeletal Ewing's sarcoma is an uncommon disease that predominantly involves
      the soft tissues of the trunk or the extremities. This article presents a patient
      with multifocal intrathoracic mass lesions involving the mediastinum and the
      lingula associated with mediastinal shift, eventually diagnosed as extraskeletal
      Ewing's sarcoma.

PMID- 16564300
TI  - Very unusual case of post-traumatic chylothorax.
AB  - Chylothorax is a rare disease caused by both traumatic and nontraumatic events.
      Chylothorax can cause cardiopulmonary abnormalities and significant nutritional,
      metabolic, and immunologic consequences. We present an exceptional case of
      chylothorax due to penetrating chest trauma. The diagnosis was made by
      thoracentesis. Conservative management with nothing by mouth and total parenteral
      nutrition failed; therefore the patient needed surgical closure of the duct leak.

PMID- 16564301
TI  - Giant hiatal hernia with gastric volvulus complicating pneumonectomy.
AB  - Gastric volvulus is a potentially lethal condition. Pneumonectomy patients have
      decreased physiologic reserve, and thus they are more susceptible to morbidity
      and mortality from postoperative complications. We report successful management
      of a patient with hiatal hernia that resulted in acute gastric volvulus after
      left pneumonectomy.

PMID- 16564302
TI  - Bouveret meets Boerhaave.
AB  - Rarely, biliary-enteric fistula can result in duodenal obstruction or Bouveret's
      syndrome. Boerhaave's syndrome is a distal esophageal rupture in the setting of
      severe emesis. This case is the first reported successful management of these
      clinical scenarios occurring simultaneously and highlights important features in
      presentation, diagnosis, and surgical treatment.

PMID- 16564303
TI  - Reconstruction of the left ventricle after previous aneurysmectomy.
AB  - Two patients recently underwent successful repeat left ventricular anterior
      aneurysmectomies at our institution. Both patients had undergone a linear repair
      at first operation. Over time severe heart failure relapsed and echocardiography
      revealed the recurrence of a voluminous antero-septo-apical aneurysm in both
      cases, associated with severe mitral regurgitation. Because of still preserved
      motion of at least three of the basal segments of the left ventricle, a repeat
      ventriculoplasty according to Dor and a restrictive mitral valve annuloplasty was
      attempted. At 6-month follow-up, the patients were in the New York Heart
      Association functional class I and II, respectively. Left ventricular end
      diastolic diameters decreased from 73 mm to 67 mm and from 81 mm to 52 mm, and
      left ventricular end-systolic diameters from 61 mm to 54 mm and from 70 mm to 34
      mm. Mitral regurgitation was absent.

PMID- 16564304
TI  - Munchhausen Syndrome simulating acute aortic dissection.
AB  - A young adult man presented to the emergency department reporting a convincing
      story for acute aortic dissection, a disorder in which diagnostic evaluations
      should occur in parallel with pharmacologic management. Transesophageal
      echocardiography demonstrated normal cardiac and aortic structures. Additional
      history was notable for extensive travel across numerous medical facilities with
      associated misrepresentation of his diagnosis and treatment. The patient was
      willing to undergo unpleasant and invasive procedures and succeeded at least once
      in the past to deceive clinicians to the point of performing a median sternotomy.
      The intentional presentation of false information leading to unnecessary
      treatments is consistent with Munchhausen Syndrome.

PMID- 16564305
TI  - Acute intraoperative malfunction of aortic valve due to surgical glue.
AB  - The use of surgical glues in aortic surgery has gained wide popularity due to
      their hemostatic and tissue reinforcing properties. Reports of acute
      complications associated with application of glue are rare. We report the case of
      a 52-year-old fragile, steroid-dependent woman who developed acute intraoperative
      dysfunction of an aortic prosthetic valve due to use of BioGlue surgical
      adhesive. A brief literature review of the acute and long-term complications of
      the glue is presented.

PMID- 16564306
TI  - Management of acute infrarenal aortic occlusion secondary to type A dissection.
AB  - Infrarenal aortic occlusion is a well described complication of type A aortic
      dissection that carries a significant mortality rate. A technique of immediate
      reperfusion of the lower extremities through an axillo-bi-femoral graft is
      described in 2 patients with good results.

PMID- 16564307
TI  - Dislocation of a stent-graft into the aortic arch during endovascular repair of a
      descending thoracic aortic aneurysm.
AB  - A 59-year-old man showed a saccular aneurysm due to a penetrating atherosclerotic
      ulcer, as well as a small type B aortic dissection located in the proximal
      descending aorta. The lesion was treated by the implantation of a stent-graft. On
      release, the stent-graft dislocated into the aortic arch. Intraoperative
      angiogram showed free perfusion of the brachiocephalic trunk and left common
      carotid artery; however, an overstenting of the carotid artery was apparent.
      Computed tomographic scan exhibited a complete covering of the supra-aortic
      vessels, and conventional, open aortic arch surgery was inevitable. A partial
      resection of the proximal part of the stent-graft was performed.

PMID- 16564308
TI  - Heterotopic heart transplant combined with postoperative Sildenafil use for the
      treatment of restrictive cardiomyopathy.
AB  - We report successful management of a 22-month-old child with restrictive
      cardiomyopathy and severe pulmonary hypertension using the heterotopic heart
      transplant technique. Additional lessons learned from postoperative management,
      including the novel use of Sildenafil (Viagra, Pfizer, NY) for controlling
      pulmonary arterial pressure are described.

PMID- 16564309
TI  - Chylothorax after internal thoracic artery harvest.
AB  - Chylothorax is a rare complication following coronary artery bypass graft
      surgery. We report a case of chylothorax that complicated a left internal
      thoracic artery harvest and review the literature regarding this subject.

PMID- 16564310
TI  - Cholesterol granuloma of the superior mediastinum.
AB  - Cholesterol granuloma develops as a response to cholesterol acting as an irritant
      and causing giant cell formation. This more commonly affects the sinuses with no
      previous report in the mediastinal region. We describe such a case in a cardiac
      surgical patient with an incidental finding of testicular lumps.

PMID- 16564311
TI  - Rupture of a synthetic VSD patch 28 years after total correction of Fallot's
      anomaly.
AB  - Patients operated on for complex congenital heart malformations need continuous
      follow-up. We present a male patient born in 1948 with Fallot's anomaly. A total
      correction was performed when he was 21 years old. Twenty-eight years after the
      operation, at routine follow-up, he presented with a significant left-to-right
      shunt because of a new ventricular septal defect. During the operation we found
      the original patch to be fractured with a central perforation. The patient
      received a new patch and has been without any clinical symptoms since.

PMID- 16564312
TI  - Bland-White-Garland syndrome in pregnancy: reoperation of ALCAPA with an internal
      thoracic radial artery "Y"-graft.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery is rare
      and more so in the adult. Reimplantation of the left main coronary into the aorta
      is successful in early life, but it may be more difficult in the adult who had a
      previous repair. We report a successful reoperation of anomalous origin of the
      left coronary artery from the pulmonary artery in an adult patient using a left
      internal thoracic and radial artery "Y"-graft. Composite arterial grafting has
      become an established and straight forward technique in coronary surgery, and it
      is appropriate and recommended for congenital lesions in adults and at any age if
      necessary.

PMID- 16564313
TI  - Extracorporeal membrane oxygenation support of a neonate with percutaneous
      femoral arterial cannulation.
AB  - We describe a neonate with hypoplastic left heart syndrome supported with
      venoarterial extracorporeal membrane oxygenation with a femoral arterial cannula.
      A 6-French straight sheath was percutaneously placed in the right femoral artery
      using the Seldinger technique. Adequate extracorporeal membrane oxygenation flows
      were achieved, and the patient was successfully de-cannulated. Femoral arterial
      cannulation in neonates is technically feasible and provides an alternative site
      for extracorporeal membrane oxygenation cannulation.

PMID- 16564314
TI  - Ascending aortic pseudoaneurysm in a patient without a sternum.

PMID- 16564315
TI  - A prominent collateral coronary artery.

PMID- 16564316
TI  - Simple and useful endoscopic technique in the re-establishment of esophageal
      patency for the treatment of a completely obstructed esophagus.
AB  - Complete esophageal obstruction by benign or malignant diseases is an extremely
      morbid condition resulting in a very poor quality of life. Nutritional support
      through gastrostomy feeding or total parenteral nutrition is required to sustain
      life for such a patient. Re-establishment of esophageal patency allows for
      resumption of oral intake resulting in a marked improvement in the quality of
      life and avoids the complications associated with nutritional support through
      alternate routes. We describe a simple, safe, and effective endoscopic technique
      in the re-establishment of esophageal luminal patency.

PMID- 16564317
TI  - Subpleural catheter placement for pain relief after thoracoscopic resection.
AB  - Infusion of local anesthetics into an extrapleural pocket results in excellent
      postoperative pain relief through a multilevel intercostal nerve blockade. This
      report describes a simple, rapid technique of subpleural catheter placement that
      lends itself well to thoracoscopic procedures.

PMID- 16564318
TI  - Use of an apical heart suction device for exposure in lung transplantation.
AB  - Cardiopulmonary bypass is not necessary for the performance of bilateral
      sequential lung transplantation in most circumstances. Inadequate exposure to the
      left hilum is occasionally the sole indication for institution of cardiopulmonary
      bypass. We report the use of a suction heart positioning device to allow lifting
      of the heart for improvement of left hilar exposure. This technique has decreased
      the need for cardiopulmonary bypass when bypass is indicated due to difficult
      operative exposure.

PMID- 16564319
TI  - "Adjustable" artificial chordal replacement for repair of mitral valve prolapse.
AB  - Achieving a stable repair of mitral valve prolapse can be difficult in complex
      pathologies, and a 5% to 20% late reoperation rate exists with leaflet resection
      and reconstruction. During an 8-year period, prolapse was managed uniformly with
      "adjustable" Gortex (W. L. Gore & Associates Inc, Flagstaff, AZ) artificial
      chordal replacement and Carpentier ring annuloplasty (Edwards Lifesciences LLC,
      Irvine, CA), without leaflet resection. Artificial chords were placed initially
      in the papillary muscles, and then after ring annuloplasty they were adjusted to
      optimize length to the prolapsing segment(s). Of 52 patients with prolapse, 100%
      were repaired successfully with artificial chords. Operative mortality was 1.9%,
      and 4, 6, and 8-year survivals were 87%, 81%, and 71%, respectively. Only 1 of 52
      patients (1.9%) experienced late failure, and this patient was re-repaired with
      artificial chords. Thus, "adjustable" artificial chordal replacement facilitates
      uniform repair of mitral valve prolapse with a low late failure rate.

PMID- 16564320
TI  - Physiologic versus anatomic repair of congenitally corrected transposition of the
      great arteries: meta-analysis of individual patient data.
AB  - The objective of this meta-analysis of individual patients' data was to compare
      the immediate outcomes of anatomic and physiologic repair of congenitally
      corrected transposition of the great arteries. Eleven nonrandomized studies,
      involving 124 patients, met the inclusion criteria for this review. The Rastelli
      type anatomic repair and the era of surgery were significantly related to the
      outcome in different tested models. Entering all variables into the logistic
      regression model showed a significant protective effect of the Rastelli type
      anatomic repair (odds ratio = 0.05, 95% confidence interval: 0.01, 0.50, p =
      0.02).

PMID- 16564321
TI  - Levosimendan in cardiac surgery: current best available evidence.
AB  - Recent upsurge in referral of patients with high perioperative risk or
      compromised left ventricular function for cardiac surgery has lead to an
      increasing use of pharmacologic support in the form of vasodilator and inotropic
      therapy to achieve improvement of tissue perfusion in the perioperative period or
      to support weaning from cardiopulmonary bypass. Traditionally, perioperatively
      used inotropic agents, epinephrine, dobutamine, and milrinone, are limited by
      significant increases in myocardial oxygen consumption, proarrhythmia, or
      neurohormonal activation. Levosimendan, a new inodilator for the treatment of
      decompensated heart failure, has also shown promise in elective therapy of
      cardiac surgical patients with high perioperative risk or compromised left
      ventricular function, as well as in rescue therapy of patients with difficult
      weaning from cardiopulmonary bypass. This review article briefly discusses the
      pharmacology of levosimendan and evaluates current best available evidence to
      assess the safety and efficacy of levosimendan usage in cardiac surgery.

PMID- 16564322
TI  - Detecting metastasis of lung cancer in mediastinal lymph nodes: the discrepancy
      between cytology and histology.

PMID- 16564324
TI  - Limited value of histopathologic prognostic factors for resected colorectal lung
      metastases.

PMID- 16564325
TI  - Postoperative renal dysfunction after on-pump versus off-pump coronary
      revascularization: role of on-pump hemodilution and transfusions.

PMID- 16564329
TI  - Anterior mitral leaflet plication.

PMID- 16564331
TI  - Angiographic patency of the radial artery conduit in coronary artery bypass
      grafting.

PMID- 16564332
TI  - Aortic arch replacement using a trifurcated graft.

PMID- 16564333
TI  - Defending the zygote: search for the ancestral animal block to polyspermy.
AB  - Fertilization is the union of a single sperm and an egg, an event that results in
      a diploid embryo. Animals use many mechanisms to achieve this ratio; the most
      prevalent involves physically blocking the fusion of subsequent sperm. Selective
      pressures to maintain monospermy have resulted in an elaboration of diverse egg
      and sperm structures. The processes employed for monospermy are as diverse as the
      animals that result from this process. Yet, the fundamental molecular
      requirements for successful monospermic fertilization are similar, implying that
      animals may have a common ancestral block to polyspermy. Here, we explore this
      hypothesis, reviewing biochemical, molecular, and genetic discoveries that lend
      support to a common ancestral mechanism. We also consider the evolution of
      alternative or radical techniques, including physiological polyspermy, with
      respect to our ability to describe a parsimonious guide to fertilization.

PMID- 16564334
TI  - Dishevelled: a mobile scaffold catalyzing development.
AB  - Wnt proteins are secreted glycoprotein ligands that regulate critical aspects of
      development, including cell proliferation, apoptosis, and cell fate. For those
      pathways downstream from the "canonical" Wnt/beta-catenin signaling, from the
      "non-canonical" or planar cell polarity (PCP), and from the Wnt-Ca(2+)/cyclic
      guanosine monophosphate (cGMP) pathway, Wnt activation of its cellular receptor,
      a member of the superfamily of G-protein-coupled receptor Frizzled family,
      requires both heterotrimeric G proteins and the phosphoprotein Dishevelled. Our
      understanding of the roles of Dishevelled proteins in development is evolving and
      most recent observations suggest that Dishevelled proteins act as scaffolds
      essential for Wnt signaling, providing docking sites for a diverse and
      interesting set of protein kinases, phosphatases, adaptor proteins, G proteins,
      and other scaffolds such as Axin. The protein-protein interactions of Dishevelled
      are dynamic, as is the spatial localization of this "toolbox" of signaling
      molecules involved in development. Much excitement awaits the elucidation of the
      complete set of tools in the toolbox and of the dynamic regulation of Dishevelled
      proteins and their interacting proteins.

PMID- 16564335
TI  - Sensory organs: making and breaking the pre-placodal region.
AB  - Sensory placodes are unique domains of thickened ectoderm in the vertebrate head
      that form important parts of the cranial sensory nervous system, contributing to
      sense organs and cranial ganglia. They generate many different cell types,
      ranging from simple lens fibers to neurons and sensory cells. Although progress
      has been made to identify cell interactions and signaling pathways that induce
      placodes at precise positions along the neural tube, little is known about how
      their precursors are specified. Here, we review the evidence that placodes arise
      from a unique territory, the pre-placodal region, distinct from other ectodermal
      derivatives. We summarize the cellular and molecular mechanisms that confer pre
      placode character and differentiate placode precursors from future neural and
      neural crest cells. We then examine the events that subdivide the pre-placodal
      region into individual placodes with distinct identity. Finally, we discuss the
      hypothesis that pre-placodal cells have acquired a state of "placode bias" that
      is necessary for their progression to mature placodes and how such bias may be
      established molecularly.

PMID- 16564336
TI  - Regulation of hepatocyte cell cycle progression and differentiation by type I
      collagen structure.
AB  - Cell behavior is strongly influenced by the extracellular matrix (ECM) to which
      cells adhere. Both chemical determinants within ECM molecules and mechanical
      properties of the ECM network regulate cellular response, including
      proliferation, differentiation, and apoptosis. Type I collagen is the most
      abundant ECM protein in the body with a complex structure that can be altered in
      vivo by proteolysis, cross-linking, and other processes. Because of collagen's
      complex and dynamic nature, it is important to define the changes in cell
      response to different collagen structures and its underlying mechanisms. This
      chapter reviews current knowledge of potential mechanisms by which type I
      collagen affects cell behavior, and it presents data that elucidate specific
      intracellular signaling pathways by which changes in type I collagen structure
      differentially regulate hepatocyte cell cycle progression and differentiation. A
      network of polymerized fibrillar type I collagen (collagen gel) induces a highly
      differentiated but growth-arrested phenotype in primary hepatocytes, whereas a
      film of monomeric collagen adsorbed to a rigid dish promotes cell cycle
      progression and dedifferentiation. Studies presented here demonstrate that
      protein kinase A (PKA) activity is significantly elevated in hepatocytes on type
      I collagen gel relative to collagen film, and inhibition of this elevated PKA
      activity can promote hepatocyte cell cycle progression on collagen gel.
      Additional studies are presented that examine changes in hepatocyte cell cycle
      progression and differentiation in response to increased rigidity of polymerized
      collagen gel by fiber cross-linking. Potential mechanisms underlying these
      cellular responses and their implications are discussed.

PMID- 16564339
TI  - Time for the renaissance of medicine in the Middle East.

PMID- 16564338
TI  - Fur seal adaptations to lactation: insights into mammary gland function.
AB  - The fur seal (Arctocephalus spp. and Callorhinus spp., members of the pinniped
      family) is a mammal with the unusual capability to modulate its lactation cycle
      by turning milk production on and off without the typical mammalian regression
      and involution of the mammary gland. Lactation has evolved from constraints
      arising from the spatial and temporal separation of infant nursing and maternal
      foraging as the mother gives birth and feeds the pup on land while acquisition of
      nutrients for milk production occurs at sea. The lactation cycle begins with the
      female fur seal undergoing a perinatal fast of approximately 1 wk, after which
      time she departs the breeding colony to forage at sea. For the remainder of the
      long lactation period (116-540 days), the mother alternates between short periods
      ashore suckling the young with longer periods of up to 4 wk of foraging at sea.
      Milk production continues while foraging at sea, but at less than 20% the rate of
      production on land. Fur seals produce one of the richest milk reported, with a
      very high lipid content contributing up to 85% of total energy. This feature
      serves as an adaptation to the young's need to produce an insulating blubber
      layer against heat loss and to serve as an energy store when the mother is away
      foraging at sea. This atypical pattern of lactation means mothers have long
      periods with no suckling stimulus and can transfer high-energy milk rapidly while
      on land to minimize time away from foraging grounds. The absence of suckling
      stimulus and milk removal during foraging does not result in the onset of
      involution with associated apoptosis of mammary secretory cells and a subsequent
      progressive breakdown of the cellular structure of the mammary gland. The
      mechanisms controlling lactation in the fur seal mammary gland have been
      investigated using molecular and cellular techniques. These findings have shed
      light on the processes by which the unique features of lactation in the fur seal
      are regulated.

PMID- 16564340
TI  - Richard Feachem's legacy to the Global Fund.

PMID- 16564341
TI  - SuperMAB on trial.

PMID- 16564337
TI  - Engineering stem cells into organs: topobiological transformations demonstrated
      by beak, feather, and other ectodermal organ morphogenesis.
AB  - To accomplish regenerative medicine, several critical issues in stem cell biology
      have to be solved, including the identification of sources, the expanding
      population, building them into organs, and assimilating them to the host.
      Although many stem cells can now differentiate along certain lineages, knowledge
      on how to use them to build organs lags behind. Here we focus on topobiological
      events that bridge this gap, for example, the regulation of number, size, axes,
      shape, arrangement, and architecture during organogenesis. Rather than reviewing
      detail molecular pathways known to disrupt organogenesis when perturbed, we
      highlight conceptual questions at the topobiological level and ask how cellular
      and molecular mechanisms can work to explain these phenomena. The avian
      integument is used as the Rosetta stone because the molecular activities are
      linked to organ forms that are visually apparent and have functional consequences
      during evolution with fossil records and extant diversity. For example, we show
      that feather pattern formation is the equilibrium of stochastic interactions
      among multiple activators and inhibitors. Although morphogens and receptors are
      coded by the genome, the result is based on the summed physical-chemical
      properties on the whole cell's surface and is self-organizing. For another
      example, we show that developing chicken and duck beaks contain differently
      configured localized growth zones (LoGZs) and can modulate chicken beaks to
      phenocopy diverse avian beaks in nature by altering the position, number, size,
      and duration of LoGZs. Different organs have their unique topology and we also
      discuss shaping mechanisms of liver and different ways of branching
      morphogenesis. Multi-primordium organs (e.g., feathers, hairs, and teeth) have
      additional topographic specificities across the body surface, an appendage field,
      or within an appendage. Promises and problems in reconstitute feather/hair
      follicles and other organs are discussed. Finally, simple modification at the
      topobiological level may lead to novel morphology for natural selection at the
      evolution level.

PMID- 16564342
TI  - Public-health challenges in the Middle East and North Africa.

PMID- 16564344
TI  - For better immunisation coverage, measure coverage better.

PMID- 16564345
TI  - Elimination of transmission of lymphatic filariasis in Egypt.

PMID- 16564346
TI  - Report of WHO's World Mental Health Survey.

PMID- 16564347
TI  - Consanguinity: implications for practice, research, and policy.

PMID- 16564348
TI  - Why the modern Middle East?

PMID- 16564349
TI  - Lihadh Al-Gazali: a leading clinical geneticist in the Middle East.

PMID- 16564350
TI  - American College of Chest Physicians' cough guidelines.

PMID- 16564351
TI  - American College of Chest Physicians' cough guidelines.

PMID- 16564352
TI  - Measurement of toxin production by Clostridium difficile.

PMID- 16564353
TI  - PROactive study.

PMID- 16564355
TI  - Debating intelligent design.

PMID- 16564356
TI  - Meniere's disease.

PMID- 16564357
TI  - Better health statistics: the Cuban experience.

PMID- 16564358
TI  - Finding a vaccine for human papillomavirus.

PMID- 16564359
TI  - The Pakistan earthquake: a personal experience.

PMID- 16564360
TI  - Reduction of vaccine-preventable communicable diseases in a Bedouin population:
      summary of a community-based intervention programme.
AB  - BACKGROUND: The Bedouin Arab population of southern Israel is in transition from
      a semi-nomadic lifestyle to permanent settlement, with many characteristics of a
      third-world population. A major outbreak of measles in the winter of 1990-91,
      with an incidence of 415.6 per 100,000 and a case fatality rate of 2.2 % among
      the Bedouin, led to the establishment of a national committee, which recommended
      an intervention programme. We report on the effect of the programme
      implementation on the reduction of vaccine-preventable communicable diseases in a
      Bedouin Arab population. METHODS: We compared immunisation coverage and incidence
      of reportable vaccine-preventable communicable diseases before and after
      implementation of the intervention programme. FINDINGS: Implementation of the
      intervention programme was associated with a marked increase in immunisation
      coverage, from 53% for first measles immunisation among those born in 1988, and
      reaching 2 years of age in 1990 at the start of the outbreak, to 90% at age 2
      years among those born in 2001. We noted a decrease in all vaccine-preventable
      communicable diseases, except for pertussis, during this period. INTERPRETATION:
      The implementation of a targeted programme to improve immunisation coverage, and
      other concomitant changes in health-care delivery, was temporally associated with
      reduction of vaccine-preventable communicable diseases in a population of Bedouin
      Arabs in Israel who are living in semi-nomadic conditions. The success of the
      programme could be applicable to semi-nomadic populations living in other areas
      of the middle east.

PMID- 16564361
TI  - Effect of yearly mass drug administration with diethylcarbamazine and albendazole
      on bancroftian filariasis in Egypt: a comprehensive assessment.
AB  - BACKGROUND: Egypt was one of the first countries to implement a national
      programme to eliminate lymphatic filariasis based on WHO's strategy of repeated
      rounds of mass drug administration (MDA) with diethylcarbamazine and albendazole
      (target population, 2.5 million in 181 localities). We assessed the effect of
      five yearly rounds of MDA on filariasis in four sentinel villages in Egypt.
      METHODS: We studied two areas with different infection rates before MDA: the
      Qalubyia study area had a low infection rate because of previous treatment with
      diethylcarbamazine; this was typical of most filariasis-endemic villages in Egypt
      before MDA. The Giza study area had a high baseline infection rate. We undertook
      repeated surveys in villages for treatment compliance and tests for
      microfilaraemia and circulating filarial antigenaemia, antibodies to filarial
      antigen Bm14 in schoolchildren, and infections in indoor-resting mosquitoes
      (assessed by PCR). FINDINGS: MDA compliance rates were excellent (>80%). In Giza
      after MDA, prevalence rates of microfilaraemia and circulating filarial
      antigenaemia fell from 11.5% to 1.2%, and from 19.0% to 4.8%, respectively
      (p<0.0001). Corresponding rates in Qalubyia fell from 3.1% to 0% and 13.6% to
      3.1%, respectively (p<0.0001). Rates of antifilarial antibody and circulating
      filarial antigenaemia in schoolchildren (aged about 7-8 years), fell from 18.3%
      to 0.2% (p<0.0001) and from 10.0% to 0.4% (p<0.0001) in Giza, respectively, and
      from 1.7% to 0% and 1.7% to 0% (both p=0.13) in Qalubyia, respectively. Mosquito
      infection rates fell from 3.07% (95% CI 2.38-3.88) to 0.19% (0.08-0.38) in Giza
      and from 4.37% (3.07-5.99) to 0% (0-0.05) in Qalubyia. INTERPRETATION: MDA
      greatly affects variables related to infection (microfilaraemia and circulating
      filarial antigenaemia prevalence rates) and transmission (antifilarial antibodies
      in young children and mosquito infection rates). Our results suggest that after
      five rounds of MDA filariasis is likely to have been eliminated in most endemic
      localities in Egypt.

PMID- 16564363
TI  - Exploring the heart of the human heart.

PMID- 16564362
TI  - Prevalence and treatment of mental disorders in Lebanon: a national
      epidemiological survey.
AB  - BACKGROUND: Mental disorders are believed to account for a large portion of
      disease burden worldwide. However, no national studies have been undertaken to
      assess this assumption in the Arab world. METHODS: As part of the WHO World
      Mental Health (WMH) Survey Initiative, a nationally representative psychiatric
      epidemiological survey of 2857 adults (aged 18 years) was done in Lebanon between
      September, 2002, and September, 2003, through a study called LEBANON (Lebanese
      Evaluation of the Burden of Ailments and Needs Of the Nation). 12-month
      prevalence and severity of DSM-IV (Diagnostic and Statistical Manual of Mental
      Disorders, fourth edition) disorders, and treatment were assessed with the WHO
      Composite International Diagnostic Interview (CIDI, version 3.0). Information was
      also obtained for sociodemographics and exposure to traumatic events in the
      Lebanon wars. FINDINGS: 308 (17.0%) of respondents met criteria for at least one
      12-month DSM-IV/CIDI disorder, 108 (27.0%) of whom were classified serious and an
      additional 112 (36.0%) moderate. Nearly half of respondents had a history of
      exposure to war-related traumatic events. Significantly elevated odds ratios (OR)
      of mood, anxiety, and impulse-control disorders were associated with two (OR 2.0
      3.6) or more (2.2-9.1) war-related traumatic events, resulting in substantially
      higher proportions of moderate and severe 12-month mental disorders in
      respondents exposed to multiple war-related traumata (16.8-20.4%) compared with
      other respondents (3.3-3.5%). Only 47 (10.9%) respondents with 12-month disorders
      obtained treatment. 85% of people were treated in the general medical sector and
      the mental-health-care system, and the rest by religious or spiritual advisers,
      counsellors, herbalists, or fortune-tellers. INTERPRETATION: Mental disorders are
      common in Lebanon, with a prevalence equivalent to that in Western Europe.
      However, the number of individuals with mental disorders who are not receiving
      treatment is considerably higher in Lebanon than in Western countries.

PMID- 16564364
TI  - Health risks at the Hajj.
AB  - Annually, millions of Muslims embark on a religious pilgrimage called the "Hajj"
      to Mecca in Saudi Arabia. The mass migration during the Hajj is unparalleled in
      scale, and pilgrims face numerous health hazards. The extreme congestion of
      people and vehicles during this time amplifies health risks, such as those from
      infectious diseases, that vary each year. Since the Hajj is dictated by the lunar
      calendar, which is shorter than the Gregorian calendar, it presents public-health
      policy planners with a moving target, demanding constant preparedness. We review
      the communicable and non-communicable hazards that pilgrims face. With the rise
      in global travel, preventing disease transmission has become paramount to avoid
      the spread of infectious diseases, including SARS (severe acute respiratory
      syndrome), avian influenza, and haemorrhagic fever. We examine the response of
      clinicians, the Saudi Ministry of Health, and Hajj authorities to these unique
      problems, and list health recommendations for prospective pilgrims.

PMID- 16564365
TI  - Familial mediterranean fever in Arabs.
AB  - Autoinflammatory diseases are a group of disorders characterised by seemingly
      unprovoked inflammation in the absence of high-titre autoantibodies or antigen
      specific T cells, and include the hereditary periodic fever syndromes. Familial
      Mediterranean fever (FMF) is an archetypal autoinflammatory disorder, which is
      autosomal recessive and has a high prevalence in non-Ashkenazi Jews, Armenians,
      Turks, and Arabs. The classic clinical picture is recurrent acute short-lived
      febrile and painful attacks with variable periods of remission. In a subset of
      patients, the disorder is complicated by amyloidosis that leads to renal failure.
      The gene responsible for FMF--MEFV--has been identified and its role in
      inflammation is being assessed. There seems to be a distinctive clinical picture
      in Arab patients with FMF, and the range and distribution of MEFV mutations is
      different from that noted in other affected ethnic groups. Here, we discuss the
      clinical and molecular aspects of FMF in Arabs.

PMID- 16564366
TI  - Muslim health-care workers and alcohol-based handrubs.

PMID- 16564367
TI  - Hodgkin's lymphoma: an obscure cause of cholestasis.

PMID- 16564368
TI  - Research: the inconspicuous, salient pillar of residency. One resident's
      perspective for prospective resident researchers.

PMID- 16564369
TI  - Safety of uvulopalatopharyngoplasty as outpatient surgery.
AB  - OBJECTIVE: Determine the admission rate and characterize the complications in
      uvulopalatopharyngoplasty (UPPP) patients scheduled to have outpatient surgery.
      STUDY DESIGN AND SETTING: Retrospective review of patients undergoing UPPP
      between 2000 and 2004 in a tertiary care setting. RESULTS: UPPP alone or in
      conjunction with tonsillectomy, septoplasty, or supraglottoplasty was carried out
      in 110 patients. Average preoperative respiratory disturbance index (RDI) was 35.
      Admission was required in 20 (18%) patients whereas 90 (82%) were discharged on
      the day of surgery. Admission due to desaturation was noted in 3 (3%) patients.
      The most common reasons for admission included pain and nausea. There were no
      major complications. CONCLUSIONS: Careful preoperative selection of patients
      should permit many patients to undergo UPPP as outpatient surgery. Factors
      requiring admission may be assessed in the early postoperative period. The rate
      of respiratory events requiring postoperative admission after UPPP is low.
      SIGNIFICANCE: UPPP can be carried out safely on an outpatient basis. EBM RATING:
      C-4.

PMID- 16564370
TI  - Comparison of the incidences of obstructive sleep apnea-hypopnea syndrome in
      African-Americans versus Caucasian-Americans.
AB  - OBJECTIVE: To determine the relative incidence of obstructive sleep apnea
      hypopnea syndrome (OSAHS) in African-Americans compared to a cohort of Caucasian
      Americans. STUDY DESIGN AND SETTING: A prospective study of 2 groups of subjects
      (287 African-Americans and 236 Caucasian-Americans) to evaluate OSAHS severity
      based on subjective symptoms and anatomic findings. Subjects were from a public
      health and fitness fair attended by approximately 80,000 people where attendees
      were invited for an ENT screening. RESULTS: Using OSAHS scores based on
      subjective symptoms and anatomic findings, the African-American group had a
      significantly higher incidence of "probable" OSAHS. In addition to symptoms of
      OSAHS, the questionnaire ascertained that African-American bed partners are more
      likely to accept loud snoring as compared to Caucasian-American bed partners.
      CONCLUSIONS: OSAHS may be more common in African-Americans, but African-American
      bed partners are more likely to accept snoring. The medical community should
      strive to increase awareness and education about OSAHS in the African-American
      community. EBM RATING: B-3b.

PMID- 16564371
TI  - Initial U.S. pilot study: palatal implants for the treatment of snoring.
AB  - OBJECTIVE: To assess efficacy of polyethylene terephthalate (PET) implants in the
      soft palate for the treatment of socially significant snoring. DESIGN: A
      prospective, interventional case series. SETTING: Hospital-based multi-specialty
      clinic. PATIENTS: Twenty-five consecutive patients with socially significant
      snoring without history of obstructive sleep apnea. INTERVENTION: Three PET
      implants were inserted into the soft palate of each patient (Pillar procedure,
      Restore Medical, Inc., St. Paul, Minnesota). MAIN OUTCOME MEASURE: Change in
      snoring severity measured by the bed partner using a 10-centimeter visual analog
      scale (VAS) where 0 = "no snoring noise" and 10 = "extreme snoring noise causing
      (the bed partner) to leave the bedroom." RESULTS: Ninety-day follow-up data was
      collected for 21 patients. Four patients had incomplete follow-up. Snoring VAS
      rated by the bed partner had a baseline mean value of 8.5 +/- 1.4, which
      decreased to 5.0 +/- 2.1 at 30 days and to 4.4 +/- 2.5 at 90 days (P < 0.001).
      All patients tolerated the procedure well and no procedure-related complications
      were observed. Two implants partially extruded in 1 patient within the 90-day
      follow-up period, for an implant partial extrusion rate of 2.7% (2/75 implants)
      and patient partial extrusion rate of 4% (1/25 patients). At 90 days, 75% of
      patients and 90% of their bed partners recommended the procedure. CONCLUSIONS: In
      this case series, PET implants into the soft palate significantly reduced snoring
      with few extrusions and no complications. Controlled studies are needed to
      confirm effectiveness and to refine patient selection criteria. EBM RATING: C-4.

PMID- 16564372
TI  - Palatal implants for the treatment of snoring: long-term results.
AB  - OBJECTIVE: To evaluate the safety and long-term effectiveness of a new treatment
      for snoring using permanent palatal implants. STUDY DESIGN: Prospective study
      with 35 patients referred to the clinic for the treatment of snoring. The
      patients were followed for 1 year, and a sleep analysis was performed and
      repeated at 360 days. During the procedure, 3 braided polyethylene terephthalate
      implants were placed in the palate of each patient. RESULTS: The average duration
      for nonnarcotic analgesics was 1.3 days. No adverse events were observed. The
      mean snoring intensity was reduced from 7.1 at baseline to 4.8 at 1 year (P <
      0.001). Bed partner satisfaction rate was very high at 70.6% after 1 year. Six
      patients (17.8%) experienced a total of 9 partial extrusions. CONCLUSIONS: The
      palatal implant system is safe, and the effectiveness in treating snoring is
      comparable to other surgical methods. Advantages are virtually no tissue damage
      and minimal patient discomfort as a result of one standardized, low-cost
      procedure. EBM RATING: C-4.

PMID- 16564373
TI  - Soft palate implants for the treatment of mild to moderate obstructive sleep
      apnea.
AB  - OBJECTIVE: To evaluate the initial short-term effectiveness of palatal implants
      in treating patients with mild to moderate obstructive sleep apnea (OSA).
      Previous published studies have focused on snoring without OSA. STUDY DESIGN: A
      prospective, nonrandomized study of 25 previously untreated patients with an
      apnea-hypopnea index (AHI) of 10 to 30 and a body mass index (BMI) of <or=30.
      Three permanent implants (Pillar; Restore Medical, St Paul, MN) were placed in
      the soft palate of each patient with a specially designed delivery tool in an
      office setting under local anesthesia after a formal polysomnography. A repeat
      polysomnography was obtained after 90 days. RESULTS: The AHI was reduced from a
      mean of 16.2 to a mean of 12.1 (P < 0.05) for the study group. Twenty of 25
      patients (80%) experienced a decrease in the AHI. Twelve of 25 patients (48%)
      showed a post-90-day implant AHI of 10 or less, a benchmark for the possible
      cessation of continuous positive airway pressure therapy. The Epworth Sleepiness
      Score decreased from 9.7 to 5.5 (P < 0.001) and the visual analog Scale of
      snoring intensity reported by bed partners decreased from 8.4 to 4.3 (P < 0.001).
      CONCLUSION: The palatal implant method can significantly improve AHI and other
      sleep-related parameters in patients with mild to moderate OSA and a BMI of
      <or=30. Short-term results are comparative to those reported for
      uvulopalatopharyngoplasty but achieved in a low-cost, single-stage, outpatient
      office setting with low morbidity. EBM RATING: C-4.

PMID- 16564374
TI  - Multilevel surgery for obstructive sleep apnea: short-term results.
AB  - OBJECTIVE: To determine the efficacy of a new multilevel surgical protocol for
      obstructive sleep apnea (OSA). STUDY DESIGN AND SETTING: Sixty patients with
      moderate to severe OSA because of multilevel pharyngeal obstruction were enrolled
      into this prospective, controlled clinical trial after clinical examination,
      endoscopy, and polysomnography. Surgery included uvulaflap, tonsillectomy, hyoid
      suspension, and radiofrequency treatment of the tongue base (group A). A second
      group did not receive hyoid suspension (group B). In both groups, nasal surgery
      was performed if necessary. Polysomnography and Epworth Sleepines Scale (ESS)
      were recorded at baseline and 2 to 15 months after surgery. RESULTS: In group A,
      the mean apnea-hypopnea index (AHI) decreased significantly after surgery (38.9
      +/- 20.0 vs 20.7 +/- 20.6, P < 0.0001), whereas in group B the AHI did not. All
      secondary variables (minimal oxygen saturation, mean oxygen saturation, arousal
      index), and the ESS significantly improved in group A with only changes in
      arousal index and ESS reaching levels of significance in group B. CONCLUSION: The
      presented protocol including the hyoid suspension proved to be effective in the
      treatment of OSA, whereas surgery without hyoid suspension was less successful.
      EBM RATING: B-2b.

PMID- 16564375
TI  - Prevalence of elevated total IgE and food allergies in a consecutive series of
      ENT pediatric patients.
AB  - OBJECTIVE: Food allergies in childhood have been found to vary in frequency from
      6% to 8% in the general population. Previous studies indicate milk allergy
      affects approximately 2.5% of infants and egg allergy has been estimated at 1.6%
      to 2.6%. Numerous allergists believe that the prevalence of food allergies is
      rising, similar to the rise in other atopic conditions. Prior studies have
      demonstrated that food-specific IgE is a useful test for diagnosing symptomatic
      allergies to certain foods, including milk and eggs, and could decrease the need
      to perform cumbersome multiple double-blind, placebo-controlled food challenges
      in children based on history alone. The purpose of this study was to determine
      the prevalence of food allergies and elevated IgE in a consecutive series of
      pediatric otolaryngology patients. STUDY DESIGN AND SETTING: ImmunoCap studies
      were drawn in a 2-year series of children undergoing ENT procedures of bilateral
      myringotomy with tubes (BMT) with or without adenoidectomy or tonsillectomy or
      adenoidectomy alone between 2001 and 2003. Sera was analyzed for increased total
      IgE antibodies, as well as specific IgE antibodies to antigens, including milk,
      egg, beef, and environmental allergens. A positive patient history or family
      history of allergy were documented. RESULTS: A total of 242 patients were
      assessed. Of the study population, milk allergy was found in 10.7%; egg white
      allergy was found in 5.0%. The prevalence of elevated IgE among participants was
      11.2%. The overall food allergy prevalence was 14.5%. CONCLUSIONS: Although we
      cannot imply causality, the study demonstrated an increased prevalence of food
      allergy in children undergoing ENT procedures, specifically milk and eggs, than
      in previous population studies. EBM RATING: C-4.

PMID- 16564376
TI  - Detection of fungi in the sinus mucosa using polymerase chain reaction.
AB  - OBJECTIVE: To compare the presence of fungi in the sinus mucosa of patients with
      and without chronic rhinosinusitis. STUDY DESIGN AND SETTING: Prospective
      observational study using polymerase chain reaction and conventional culture to
      detect fungi in the sinus mucosa. Middle meatus mucosal samples were collected
      from 31 patients with chronic rhinosinusitis and 14 control subjects. RESULTS:
      Fungi were detected in 6.5% of subjects with chronic rhinosinusitis and in none
      of the control subjects using polymerase chain reaction. Fungi were detected in
      29% of subjects with the combination of inhalant allergies, nasal polyposis, and
      asthma. Fungi were detected in none of the subjects without the combination of
      these three comorbidities (P = 0.03). CONCLUSION: Polymerase chain reaction assay
      appears to be able to detect fungi in chronic rhinosinusitis. SIGNIFICANCE: Fungi
      may not be implicated in the pathogenesis of most chronic rhinosinusitis. EBM
      RATING: B-3b.

PMID- 16564377
TI  - Repetitive endoscopic sinus surgery failure: a role for radical surgery?
AB  - OBJECTIVES: Endoscopic sinus surgery (ESS) is considered to be the golden
      standard for surgery in patients with chronic rhinosinusitis and nasal polyposis.
      However, there is still a small group of patients unresponsive despite repetitive
      surgery. Radical surgery aimed at reduction of the inflammatory burden and
      optimization of drainage of the sinuses has been suggested as a last resort for
      these patients. STUDY DESIGN: A prospective, questionnaire-based study was
      conducted in a group of 23 patients who underwent Denker's procedure for
      refractory chronic rhinosinusitis. Symptoms were evaluated before Denker's
      procedure and 12 months and 2 years after surgery. RESULTS: Patients reported
      improvement of feelings of congestion in 74%, rhinorrhea in 70%, and nasal
      obstruction in 60% of the cases. The following postoperative improvements were
      statistically significant: rhinorrhea (P = 0.001), feelings of congestion (P =
      0.02), and nasal obstruction (P = 0.03). Reduced olfactory perception and asthma
      did not improve. CONCLUSION: Radical surgery may be a viable treatment option in
      case of recurrent ESS failure. EBM RATING: C-4.

PMID- 16564378
TI  - Incidence of skull base and orbital erosion in allergic fungal rhinosinusitis
      (AFRS) and non-AFRS.
AB  - OBJECTIVE: To compare the incidence of bony erosion associated with allergic
      fungal rhinosinusitis (AFRS) with the incidence of bony erosion seen in other
      types of inflammatory sinusitis. STUDY DESIGN: Retrospective review. RESULTS:
      AFRS was diagnosed in 27 patients, and 15/27 (56%) had bony skull base or orbital
      erosion. Non-AFRS chronic sinusitis required surgery in 158 patients, but only 8
      (5%) had bony skull base or orbital erosion (P < 0.01). AFRS patients were 12.6
      times (P < 0.01) more likely to have bony erosion than non-AFRS patients. African
      American males were 15.0 times (P < 0.01) more likely to have bony erosion than
      whites and African American females combined. CONCLUSION: Bony erosion with
      intracranial and intraorbital extension is much more common in AFRS than all
      other types of inflammatory sinusitis combined. African American males have a
      higher incidence of AFRS, as well as intracranial and intraorbital extension. EBM
      RATING: C-4.

PMID- 16564379
TI  - Histology of the nasal septal swell body (septal turbinate).
AB  - OBJECTIVE: To analyze the vascular and glandular elements of the nasal septal
      swell body (NSB) and quantitatively compare these to the inferior turbinate (IT)
      and non-swell body portion of septum. STUDY DESIGN: Fourteen healthy adults
      undergoing septoplasty and IT reduction were submitted to unilateral biopsies of
      the NSB, the adjacent inferior turbinate, and inferior septum. Photomicrography
      with morphometric analysis was used to determine the relative area proportions of
      each tissue type. RESULTS: NSB was rich in seromucinous glands (49.9% +/- 7.0%)
      compared to IT (19.9% +/- 5.5%), P < 0.01. Conversely, IT mucosa demonstrated
      increased area proportion of venous sinusoids (28.3 +/- 13.9) compared to NSB
      (10.0 +/- 6.0), P < 0.01. Inferior septal mucosa had glandular and vascular
      elements similar in proportion to that of NSB. CONCLUSIONS AND SIGNIFICANCE: NSB
      is a highly glandular structure of the anterior-superior septum, with moderate
      proportion of venous sinusoids. Located at the distal valve segment, the NSB
      appears structured for secretory function and vasoactive airflow regulation.

PMID- 16564380
TI  - Familial aggregation of sinonasal polyps correlates with severity of disease.
AB  - OBJECTIVE: Investigate familial aggregation of sinonasal polyps (NP) and
      correlate the severity of chronic rhinosinusitis (CRS) with a family history of
      NP. STUDY DESIGN AND SETTING: A questionnaire documenting NP, asthma, or aspirin
      intolerance was completed by 174 CRS patients. Severity of sinus disease was
      stratified as isolated NP, NP with concomitant asthma, and Samter's triad
      (polyps, asthma, and aspirin intolerance). RESULTS: Compared to controls, CRS
      patients had a higher incidence of a family history of NP. Additionally, patients
      stratified with severe CRS had a higher incidence of relatives with NPs.
      CONCLUSIONS: Familial aggregation of NP is demonstrated in CRS patients and
      correlates with disease severity. EBM RATING: B-2b.

PMID- 16564381
TI  - Nasal expiratory sound analysis in healthy people.
AB  - OBJECTIVE: To evaluate the practicability of Odiosoft-Rhino (OR), a new
      experimental method for assessing the nasal airflow and resistance, in normal
      subjects and to compare the results with acoustic rhinometry (AR) findings. STUDY
      DESIGN AND SETTING: OR and AR were carried out in 72 healthy subjects. Their
      visual analogue scales of nasal obstruction, minimal cross sectional areas
      (MCA(1) and MCA(2)), and nasal expiration sounds were analyzed and noted for both
      nasal cavities. RESULTS: Statistically significant correlations (P < 0.05) were
      found between OR and AR in 2,000 to 4,000 Hz and 4,000 to 6,000 Hz with MCA(1)
      and MCA(2). CONCLUSIONS: OR is a noninvasive and rapid test. It is easy to carry
      out and requires little patient cooperation. It seems that it may give compatible
      results with other reliable methods that assess nasal airflow. SIGNIFICANCE: We
      assume that OR is a sensitive method for evaluating nasal airflow in normal
      subjects in an easy way. EBM RATING: A-1b.

PMID- 16564382
TI  - The impact of atopy, sinus opacification, and nasal patency on quality of life in
      patients with severe nasal polyposis.
AB  - OBJECTIVES: Nasal polyposis has a great impact on the quality of life. The aim of
      this study was to evaluate the association between quality of life and atopy,
      sinus opacification, and nasal patency in severe nasal polyposis. METHODS: One
      hundred nine patients completed the Medical Outcome Study Short Form-36 (SF-36)
      survey. Symptoms, polyp size, atopy, nasal patency, and sinus opacification were
      also scored. RESULTS: Patients showed worse scores in all SF-36 domains, except
      for physical functioning, compared with Spanish population. Atopic patients had
      worse scores in role physical, body pain, vitality, and mental health than
      nonatopic patients. Atopic patients showed lower physical component summary (44.7
      +/- 1.1) and mental component summary (38.4 +/- 1.0) than nonatopic patients
      (48.3 +/- 1.6, 40.6 +/- 1.3; P < 0.05), respectively. There were no correlations
      between quality of life and symptoms, polyp size, CT scan, nasal patency, and
      atopy. CONCLUSION: Nasal polyposis has a considerable impact on quality of life
      and atopy worsens this impact. EBM RATING: C-4.

PMID- 16564383
TI  - Denervated or innervated flaps for the lower lip reconstruction? Are they really
      different to get a good result?
AB  - OBJECTIVE: This study compares innervated and denervated flaps for the lower lip
      reconstruction in terms of oral sphincter function and sensation. STUDY DESIGN
      AND SETTING: A prospective trial. METHODS: This study was carried out on 31
      patients with lower lip carcinoma. They were divided in 2 groups: 18 patients
      with denervated local flaps and 13 patients with innervated flaps. During the
      follow-up period, all patients were evaluated by electromyography tests and an
      assessment of the sensation on the lower lip and sphincter function was
      undertaken by clinical parameters. RESULTS: Compound muscle action potential
      (CMAP) was obtained in all patients. The amplitudes of CMAP were below normal and
      the values for distal motor latency (DML) were slightly longer than normal
      values. Interference patterns were observed on whistling in all cases. There were
      no differences in terms of sphincteric function in each group. CONCLUSIONS: The
      denervated random local flaps used for the lower lip reconstruction have no
      functional inferiority when compared to the innervated-pedicled local flaps.
      SIGNIFICANCE: This study demonstrates that denervated flaps can be employed for a
      functional lip reconstruction. EBM RATING: B-2b.

PMID- 16564384
TI  - Perceptual voice characteristics in pediatric unilateral vocal fold paralysis.
AB  - OBJECTIVE: To describe the voice characteristics of pediatric unilateral vocal
      fold paralysis (UVFP). STUDY DESIGN AND SETTING: Retrospective series from a
      children's hospital, 1996 to present. RESULTS: Forty-two patients with a mean age
      of 7.1 years were diagnosed with UVFP in our voice clinic (prevalence = 5.4%).
      Paralysis was left sided in 88%, and was most commonly seen after cardiac surgery
      (28.5%) and prolonged intubation/prematurity (16.7%). Voice analysis showed a
      moderate degree of breathiness, mild-to-moderate hoarseness and straining, mild
      muscle tension, and soft loudness. Twenty-six percent of patients required
      surgical intervention, including injection into the paralyzed fold (7 patients)
      and medialization thyroplasty (4 patients). Pre-operatively, breathiness was
      worse (P < .05) in patients undergoing surgical intervention. CONCLUSIONS: Voice
      characteristics of pediatric UVFP include increased breathiness, hoarseness,
      straining, muscle tension, and soft loudness. One-fourth of patients underwent
      surgical intervention; breathiness was the predominant abnormal voice
      characteristic in the operative cohort. SIGNIFICANCE: The voice characteristics
      of pediatric patients with UVFP are described. EBM RATING: C-4.

PMID- 16564386
TI  - Histologic evaluation of intracordal autologous cartilage injection in the
      paralyzed canine vocal fold at two and three years.
AB  - OBJECTIVE: Intracordal injection for vocal fold augmentation is easy and simple
      and does not require a cervical skin incision. We reported previously on the 1
      year results of injected autologous auricular cartilage for volumetric
      augmentation in paralyzed canine vocal cord. This study evaluates the long-term
      histomorphologic results of injected autologous auricular cartilage for the
      augmentation of the paralyzed canine vocal fold at 2 and 3 years. STUDY DESIGN
      AND SETTING: A prospective trial of autologous cartilage augmentation of vocal
      cord in animal model. Five dogs were operated on. A piece of auricular cartilage
      was harvested from the ear and minced into tiny chips with a scalpel. Fat was
      harvested from inguinal area and minced with a scalpel. The minced cartilage and
      fat-paste (0.2 ml) was injected using a pressure syringe into the paralyzed
      thyroarytenoid muscle using direct laryngoscopy. Three animals were sacrificed at
      2 years, two at 3 years. Each subject underwent laryngectomy and serial coronal
      sections of paraffin blocks from the posterior vocal fold were made. RESULTS:
      There was no significant complications perioperatively or postoperatively. The
      injected cartilage that seemed to have lost viability existed in the vocalis
      muscles until 36 months. Fibrotic change was exhibited in the surrounding
      injected cartilage. There were no differences between 2 and 3 years in
      histomorphologic results of the injected cartilage. CONCLUSION: The autologous
      auricular cartilage graft is well tolerated and may be a very effective material
      for long-term volumetric augmentation in the paralyzed vocal cord. EBM RATING: C
      4.

PMID- 16564385
TI  - Clinicopathologic and immunohistochemical study of intraoral mucoepidermoid
      carcinoma.
AB  - OBJECTIVE: The purpose of this study is to assess the clinicopathologic and
      immunohistochemical features of intraoral mucoepidermoid carcinomas and its
      relationship with the prognosis. STUDY DESIGN AND SETTING: From 1953 to 1993, 27
      patients with intraoral mucoepidermoid carcinomas surgically treated were
      selected for this study. Clinical data were obtained from the medical records,
      the microscopic slides were reviewed, the tumors were graded, and
      immunohistochemical analysis for p53, PCNA, cerbB-2, and CEA were carried out.
      RESULTS: The tumors were more frequent in patients between 40 and 60 years of age
      (40.7%), without gender predilection. Hard palate was the most common site with
      13 cases (48%). T2 was the more frequent stage (48%) and 2 patients (7.4%) were
      staged as N+. Most tumors (48%) were classified as low grade of malignancy. The
      expression of PCNA was associated to high-grade tumors (P = .00610) and c-erbB-2
      to low grade tumors (P = .03958). No recurrence was noted in most of the cases
      (22 cases, 81.5%). Three cases (11.1%), however, showed local recurrence and 2
      patients (7.4%) died because of the disease. The analysis of the overall survival
      rate showed that male patients (P = .04249), stage N (P = .05948), high grade of
      malignancy (P = .0009), strong expression of PCNA (P = .09128), and weak
      expression of c-erbB-2 (P = .03334) had the lowest survival rates. CONCLUSION:
      Our results showed that patients with intraoral mucoepidermoid carcinoma had a
      reduced survival expectation if they were of the male gender, with regional
      metastasis, high grade of malignancy, strong expression of PCNA and weak
      expression of c-erbB-2. EBM RATING: C-4.

PMID- 16564387
TI  - Clinical characteristics and survival for major salivary gland malignancies in
      children.
AB  - OBJECTIVE: Determine presentation and survival rates for malignant pediatric
      salivary gland neoplasms. METHODS: All cases of malignant neoplasms involving the
      parotid or submandibular gland in patients ages birth to 18 years were extracted
      from the Surveillance, Epidemiology, and End Results database (1988-2001).
      Variables included age, gender, tumor histology, size, follow-up time, and vital
      status. Kaplan-Meier survival curves were constructed. RESULTS: 113 primary
      salivary gland malignancies (103 parotid, 10 submandibular) were identified. Mean
      age at presentation was 13.2 years. Female:male ratio of 5:4. Mean tumor size was
      2.5 cm. Among parotid tumors, there were 44 (43%) mucoepidermoid carcinomas and
      35 (34%) acinic cell carcinomas. At a mean follow-up of 69.4 months, 6 (5.8%)
      patients with parotid malignancy were deceased; none of the submandibular
      malignancies were fatal. Mean Kaplan-Meier survival for parotid gland lesions was
      153 months, with rhabdomyosarcomas exhibiting significantly worse survivals as
      compared to other malignancies (P < 0.001, log-rank test). CONCLUSIONS: Both
      epithelial and mesenchymal tumors present in the pediatric salivary gland.
      Survival for both parotid and submandibular gland malignancies is good in
      children. EBM RATING: C-4.

PMID- 16564388
TI  - Color doppler ultrasonography is a reliable predictor of free tissue transfer
      outcomes in head and neck reconstruction.
AB  - OBJECTIVE: The purpose of our investigation was to report our experience with a
      color flow doppler (CFD) ultrasonography for postoperative monitoring of free
      tissue transfers. METHODS: A retrospective analysis of head and neck free tissue
      transfers at a single institution between 2000 and 2005 (n = 84; 80 successful, 4
      failures). CFD measured blood flow velocity (cm/sec) and resistance to flow in
      the pedicle vein and artery on postoperative days 1, 3, and 7. RESULTS: Analysis
      of artery/vein ratio revealed vascular congestion by postoperative day 3 which
      later resolved. In flap failures, there was a significant reduction (P < 0.05) in
      venous blood flow by postoperative day 3. Waveform morphology representing
      vascular resistance and origin of donor flap did not correlate with flap outcome
      (r(2) = 0.23 and 0.44 respectively). CONCLUSION: Postoperative monitoring of free
      tissue transfers may allow for detection of poor perfusion. CFD is an objective
      method of studying blood flow postoperatively. EBM RATING: C-4.

PMID- 16564389
TI  - Analysis of prognostic factors of nasopharyngeal carcinoma: impact of in situ
      hybridization for Epstein-Barr virus encoded small RNA 1.
AB  - OBJECTIVES: To evaluate the impact of clinical, histopathological, and molecular
      biological parameters on the prognosis of nasopharyngeal carcinoma (NPC). STUDY
      DESIGN AND SETTING: The clinical records of 48 patients with a diagnosis of NPC
      were retrospectively reviewed. In situ hybridization for Epstein-Barr virus
      encoded small RNA 1 (EBER-ISH) was applied for 30 paraffin-embedded specimens
      available. Prognostic factors of NPC were meticulously analyzed. RESULTS: The
      EBER-ISH signal was shown to be highly significant as a favorable prognostic
      factor (P = 0.007). Although EBV was more commonly associated with Type III NPC,
      EBER-ISH-positive Type I-II NPC had also significantly better survival rate than
      EBER-ISH-negative Type I-II NPC (P = 0.036). CONCLUSIONS: In addition to the WHO
      histopathological grade, the 1997 UICC staging, nodal status, and distant
      metastasis at presentation, the EBER-ISH signal was shown to be significant as a
      prognostic factor. SIGNIFICANCE: This is the first report to describe the EBER
      ISH as an independent prognostic factor of NPC regardless of histopathology. EBM
      RATING: B-2b.

PMID- 16564391
TI  - Contralateral cervical lymph node metastases in pyriform sinus carcinoma.
AB  - OBJECTIVE: We designed a retrospective study to evaluate the incidence of
      contralateral neck metastases in squamous cell carcinoma of the pyriform sinus.
      STUDY DESIGN AND SETTING: Sixty-three patients with strictly unilateral squamous
      cell carcinoma of the pyriform sinus who underwent bilateral neck dissection at
      the time of primary surgery were included in this study. The medical records of
      all patients were reviewed. A multivariate statistical analysis was performed,
      considering some clinical and histologic parameters of T stage and N stage in
      relation to contralateral neck metastases. RESULTS: Contralateral neck metastases
      were histopathologically confirmed in more than 20% of the cases examined (13 out
      of 63 patients), of whom 3 were clinically staged as N2c, 2 N2b, 5 N2a, 2 N1 and
      1 N0. The percentage of occult contralateral neck metastases was 77% (10/13
      cases). Poorly differentiated tumors (P= .02) and the involvement of the lateral
      wall (P= .036) showed a statistically significant correlation with stage pN2c.
      Also T size and ipsilateral N stage were associated with the presence of
      contralateral neck metastases. CONCLUSIONS: Our data suggest that elective
      bilateral neck dissection is recommended in patients with locally advanced
      squamous cell carcinoma of the pyriform sinus. EBM RATING: C-4.

PMID- 16564390
TI  - Acute parotitis as a complication of fine-needle aspiration in Warthin's tumor. A
      unique finding of a 3-year experience with parotid tumor aspiration.
AB  - OBJECTIVE/HYPOTHESIS: Fine needle aspiration (FNA) is an accurate, cost-effective
      tool for the study of salivary gland lesions. Although complications are
      extremely rare, salivary gland FNA can lead to hemorrhage, facial nerve injury,
      and cellulitis at the needle puncture site. Some studies suggest that FNA can
      cause infarction or metaplastic transformation of benign Warthin's tumors. We
      review our recent experience with FNA of the parotid gland, focusing on possible
      complications and pitfalls. STUDY DESIGN AND SETTING: The medical records of all
      patients who underwent FNA of the parotid gland from 2000 to 2002 in the
      Department of Otolaryngology-Head and Neck Surgery of a major tertiary-care
      referral center were reviewed. Cytological results were compared to the
      histological diagnosis and complications were recorded. RESULTS: Of the 256
      lesions aspirated, 99 patients (39%), were cytologically diagnosed as benign
      tumors, including 31 (12%) Warthin's tumors, of which 16/17 resected and
      confirmed histologically. Five patients with Warthin's tumor had post-FNA
      parotitis and were treated accordingly. CONCLUSIONS: The combination of cystic
      spaces surrounded by oncocytic cells and a poor blood supply makes the tumor
      susceptible to infarction and inflammation. Our findings indicate that FNA is a
      strong and reliable tool in the investigation of the salivary glands.
      Nevertheless, when Warthin's tumor is clinically suspected on the basis of its
      location (tail of the parotid gland), cystic texture, patient sex (male) and age,
      one should consider parotitis as a possible complication. EBM RATING: C-4.

PMID- 16564392
TI  - Cytogenetic analysis of sinonasal carcinomas.
AB  - BACKGROUND: Sinonasal carcinomas, including nonkeratinizing (NK) squamous cell
      carcinoma (SCC) and sinonasal undifferentiated carcinoma (SNUC), are uncommon
      malignant neoplasms arising from the Schneiderian respiratory epithelium of the
      nasal cavity and paranasal sinuses. Due to their low frequency, the cytogenetic
      data on these tumors is limited. METHODS: Seventeen patients who were operated on
      in our institution for extirpation of paranasal carcinomas were enrolled in this
      study. Fourteen pathologically confirmed samples of sinonasal carcinomas were
      cytogenetically analyzed using G-banding techniques after short-term culture.
      Three samples did not grow on culture. RESULTS: Five of the 14 sinonasal
      carcinomas had an abnormal karyotype (36%). Of the 9 NK SCCs, 3 had abnormal
      karyotypes with numerical and structural chromosomal anomalies. Of the 5 patients
      with SNUC, 2 had an abnormal karyotype. One case of SNUC had a diploid complex
      karyotype. Another case of SNUC had a near triploid composite karyotype with 60
      69 chromosomes. The chromosome arms that involved frequent breakpoint and
      rearrangements were: 1p, 6p, 7p, and 12q. We found that 3 of the 3 patients who
      died of disease displayed an abnormal karyotype, whereas 2 of the 11 patients who
      are alive displayed an abnormal karyotype (P = 0.027). CONCLUSIONS: The study
      revealed that more than a third of the paranasal carcinomas carry an abnormal
      karyotype. No specific common aberrations were found in these tumors. To our
      knowledge this is the first attempt to investigate sinonasal squamous and
      undifferentiated carcinomas on a genetic level using G-banding technique.
      Additional studies are required in order to determine whether cytogenetic data
      may serve as an adjunct to conventional pathology for the diagnosis and prognosis
      assessment of these rare and highly aggressive tumors.

PMID- 16564393
TI  - Malignant lymphoepithelial lesions of the salivary gland.
AB  - OBJECTIVES: To describe a relatively large series of patients with uncommon
      malignant lymphoepithelial lesions (MLEL) in the salivary glands, to present
      treatment-outcome data to support therapeutic decision-making, and to evaluate
      the incidence of co-occurrence of MLEL and Epstein-Barr virus (EBV). STUDY DESIGN
      AND SETTING: Ten patients with MLEL were treated between 1987 and 2002. All
      lesions were surgically removed, with or without neck dissection, and the
      patients treated with radiotherapy or radiotherapy and chemotherapy.
      Histopathology and in situ hybridization studies for EBV-encoded RNA (EBER1) were
      performed. RESULTS: With aggressive treatment, outcomes were good, regardless of
      the presenting stage, except when distal metastases were present. All 10 patients
      tested positive for EBV. CONCLUSION AND SIGNIFICANCE: This and previous
      investigations support the use of aggressive surgical excision of the tumor and
      local metastases and radiotherapy or radiotherapy and chemotherapy, as optimal
      treatment for MLEL. The EBV finding may indicate a role for EBV in the
      pathogenesis of MLEL. EBM RATING: C-4.

PMID- 16564394
TI  - Incidence of spontaneous hearing threshold shifts during modern concert
      performances.
AB  - OBJECTIVES: Concerts have long periods of intense sound with short break
      intervals. Hearing concerns are well known to performers; concertgoers largely
      ignore them. Preperformance and postperformance audiograms were compared to
      assess hearing threshold shifts with and without earplugs. METHODS: A
      prospective, randomized study in which 29 volunteers attended 3 concerts,
      encompassing 3 music genres. Audiograms, seating location, sound intensity, and
      earplug-use data were collected. Data were analyzed to determine frequency test
      retest variability. RESULTS: Sound levels averaged 99.8 dBA, and the maximum was
      125.6 dBA. Sixty-four percent (9/14) of participants without earplugs showed
      significant threshold shifts compared with 27% (4/15) of those using earplugs. No
      significant differences existed between music genres or seating location.
      CONCLUSIONS: This study showed a high incidence of threshold shifts in
      unprotected concertgoers. Sound levels exceeded all Occupational Safety and
      Health Act rules despite standardized sound systems. A significant reduction in
      threshold shifts was seen with the use of earplugs. EBM RATING: A-1b.

PMID- 16564395
TI  - Hearing loss with stapedotomy and treated otitis media.
AB  - OBJECTIVE: To determine if treated Pseudomonas aeruginosa otitis media (PA OM)
      increases the risk of sensorineural hearing loss (SNHL) with stapedotomy. STUDY
      DESIGN AND SETTING: PA OM was induced in 28 guinea pigs. Half of the animals
      underwent unilateral stapedotomy before antibiotic therapy (untreated), and half
      underwent stapedotomy after treatment (treated). Control animals underwent saline
      injections followed by stapedotomy. Electrocochleographic thresholds were
      measured before and after stapedotomy. Temporal bones were analyzed
      histomorphologically. RESULTS: Less SNHL was seen after stapedotomy in treated
      ears than in untreated ears (P = 0.0268). SNHL after stapedotomy in treated ears
      was similar to controls (P = 0.9370). Severe damage to cochlear outer hair cells
      was found in untreated ears. CONCLUSIONS: Ears with PA OM treated previously are
      not at increased risk of SNHL with stapedotomy. SIGNIFICANCE: Stapedotomy may be
      carried out with caution in the setting of inactive, chronic OM.

PMID- 16564396
TI  - The association between positional vertebral and basilar artery flow lesion and
      prevalence of vertigo in patients with cervical spondylosis.
AB  - OBJECTIVE: The aim of our investigations was to characterize the relationship
      between basilar artery (BA) flow velocity in patients with cervical spondylosis
      and age, grade of radiological changes, prevalence of vertigo, and decreased
      blood flow velocity through vertebral arteries (VA) after head rotation. STUDY
      DESIGN AND SETTING: A prospective, controlled study in academic neurotology was
      conducted. We examined 80 patients with radiological evidence of cervical
      spondylosis. Forty patients complained of positional vertigo lasting more than 6
      months. Patients were examined by transcranial Doppler ultrasound with head
      rotations. RESULTS: We showed significant association between velocity flow in
      basilar artery after neck rotation and age, prevalence of vertigo, grade of
      radiological changes, and positional vertebral artery flow lesion. CONCLUSION:
      Spondylotic-induced VA compression may be the reason for decreased blood flow
      velocity in the basilar artery during head rotation, which may be of particular
      importance for older patients, especially complaining of vertigo. SIGNIFICANCE:
      Every patient with high-grade cervical spondylosis, especially complaining of
      vertigo, should be examined by using TCD (transcranial Doppler) with head
      rotations. In case of positional blood flow reduction during head rotation,
      further angiographic examination should be undertaken so as to plan suitable
      treatment. EBM RATING: C-4.

PMID- 16564397
TI  - Computed tomography in the diagnosis of otosclerosis.
AB  - OBJECTIVES: To identify the main tomographic findings of otosclerosis and to
      evaluate the usefulness of high-resolution computed tomography as a diagnostic
      method for this osteodystrophy. STUDY DESIGN AND SETTING: A prospective and
      multicenter study consisting of computed tomography (CT) of the temporal bone was
      conducted on 54 patients with a clinical and surgical diagnosis of otosclerosis.
      Twenty-two patients were included in the control group. RESULTS: The CT scan was
      positive in 87% of the patients. The tomographic findings were mainly bilateral
      and fenestral foci were more prevalent. CONCLUSIONS: CT showed a high rate of
      positivity, mainly for fenestral lesions. Foci anterior to the oval window were
      the most prevalent in this population. SIGNIFICANCE: CT is useful as a diagnostic
      method and therapeutic indicator of otosclerosis. EBM RATING: B-3b.

PMID- 16564398
TI  - Chronic cough: state-of-the-art review.
AB  - Cough is the most common presenting complaint in adults seeking medical treatment
      in an ambulatory setting. Chronic cough (persisting greater than 3 weeks) can be
      associated with myriad diseases that may overlap multiple medical specialties.
      For this reason, a thorough assessment of the patient with chronic cough relies
      on a multidisciplinary approach and close cooperation between pulmonary medicine,
      gastroenterology, and otolaryngology. Despite this daunting task, success can be
      achieved in up to 90% of patients with chronic cough if a systematic and thorough
      approach is used. The purpose of this review is to summarize the state-of-the-art
      in the diagnosis and treatment of chronic cough for the practicing
      otolaryngologist.

PMID- 16564400
TI  - Twenty year follow-up of ciliary mobility after bilateral inferior turbinectomy
      for allergic rhinitis using saccharin.

PMID- 16564399
TI  - Fibromuscular dysplasia of the internal carotid artery causing pulsatile
      tinnitus.

PMID- 16564401
TI  - Psammomatoid ossifying fibroma of sinonasal tract.

PMID- 16564402
TI  - Oncocytoma in the parotid gland presenting a remarkable increase in
      fluorodeoxyglucose uptake on positron emission tomography.

PMID- 16564403
TI  - Parathyroid adenoma disclosed by a massive cervical hematoma.

PMID- 16564404
TI  - Invasive fungal adenoiditis.

PMID- 16564405
TI  - Patient healing vs customer satisfaction.

PMID- 16564408
TI  - Clinically relevant physiology of the neonate.
AB  - During the 4- to 6-week neonatal period (birth to weaning), the physiology of
      canine and feline neonates undergoes dramatic change. Despite the neonate having
      the appearance of a miniature adult, their unique physiology has a significant
      impact on physical examination and laboratory test interpretation and may limit
      diagnostic capabilities and therapeutic options. In this article, the most
      striking physiologic differences between neonatal and adult body systems are
      discussed with respect to the resulting clinical implications.

PMID- 16564406
TI  - Age-related histopathologic changes in the human cochlea.

PMID- 16564409
TI  - Recent advances in small animal genetics.
AB  - The whole genome sequence of the dog is complete, and partial sequencing of the
      cat genome is underway. Sequences allow the molecular basis for inherited
      diseases to be more easily determined, leading to development of DNA tests to
      verify carrier and affected states as well as potential gene therapy for the
      treatment of those diseases. To help veterinarians provide genetic services to
      their clients, the molecular genetic tests currently available are listed in this
      article. In addition, cloning of small animals is now available to clients on a
      commercial basis. Information about the cloning process and possible health
      issues in clones are discussed.

PMID- 16564410
TI  - Pediatric neurology of the dog and cat.
AB  - The neurologic examination in the puppy or kitten can be a challenging
      experience. Understanding the development of behavior reflexes and movement in
      puppies and kittens enables us to overcome some of these challenges and to
      recognize the neurologically abnormal patient. Subsequently,we can identify the
      neuroanatomic localization and generate a differential diagnosis list. This
      article first reviews the pediatric neurologic examination and then discusses
      diseases unique to these individuals.

PMID- 16564411
TI  - Congenital heart diseases of puppies and kittens.
AB  - Congenital heart disease (CHD) is defined as a morphologic defect of the heart or
      associated great vessels present at birth. Abnormalities are caused by
      alterations or arrests in particular phases of embryonic development of the fetal
      heart. The term congenital does not imply that the defect was inherited, and the
      defect may have occurred spontaneously or secondary to a drug or toxin. By
      studying families of animals with specific CHDs, many defects have also been
      shown to be heritable.Additionally, if the defect was caused by a spontaneous de
      novo mutation,that individual has the potential to transmit the mutation to
      offspring. The diagnosis of CHD is important not only to the health of the
      patient but to eliminate affected individuals from the breeding pool.

PMID- 16564412
TI  - Selected topics in pediatric gastroenterology.
AB  - This article discusses some of the more common gastrointestinal problems
      encountered in pediatric patients. Topics include infectious and endoparasitic
      disorders, congenital esophageal and hepatic disorders, and acute or chronic
      intestinal diseases. Diagnostic criteria as well as treatment guidelines are
      presented.

PMID- 16564413
TI  - Pediatric endocrinology.
AB  - Endocrine and metabolic disorders affecting puppies and kittens from birth until
      6 months of age may manifest as clinical problems related to growth or to water
      metabolism (polydipsia and polyuria). Most commonly,endocrine and metabolic
      disorders affect growth of the animal,and puppies are often presented to the
      veterinarian for assessment of delayed or aberrant growth. Other endocrine
      disorders of small animals,such as juvenile-onset diabetes insipidus or diabetes
      mellitus, affect water metabolism, resulting in excessive thirst and urination
      and resultant difficulty in house-breaking.

PMID- 16564415
TI  - Disorders of sexual differentiation in puppies and kittens: a diagnostic and
      clinical approach.
AB  - As in all domestic mammals, sexual differentiation in dogs and cats starts early
      in the embryonic period prenatally and continues into early postnatal life. The
      result of such a process is, however, not evident until after puberty,a time when
      the entire reproductive system undergoes significant changes. Normality of sexual
      differentiation is difficult to observe in neonates of small animals, with the
      only gender difference being a slightly longer anogenital distance in male (13-15
      mm) versus female (7-8 mm)animals. Early diagnosis of deviations from normality
      can spare breeders the time and effort devoted to raising an animal that may turn
      out to be unsuitable for becoming part of the reproductive stock and may spare
      owners the concern for a pet whose health may be unnecessarily threatened by
      failing to remove a malformed reproductive system early in life. This article
      reviews the incidence, clinical and gross anatomic features,and diagnostic
      approaches that veterinarians can use to address inborn errors of the
      reproductive system of dogs and cats, highlighting those malformations that bear
      clinical relevance and may become manifest from birth until puberty.

PMID- 16564414
TI  - Topics in pediatric dermatology.
AB  - Skin conditions of puppies and kittens are often infectious, such as
      ectoparasites or dermatophytosis. Hereditary and congenital skin problems are
      often detected at an early age. Young animals may be more prone to toxicity from
      medications, and labels should be read carefully for age limits. Husbandry
      factors, including nutrition, ectoparasites,temperature and humidity, cleaning
      products, and bedding, should be considered. Fleas are still a common problem
      despite recent improvements in flea control and can be debilitating in young
      animals because of blood loss.

PMID- 16564416
TI  - Current vaccination strategies in puppies and kittens.
AB  - Motivation in writing this article stems from many things: a lack of time spent
      in the veterinary curriculum discussing vaccines, a growing concern(by the
      general public and the veterinary community) regarding adverse reactions
      associated with vaccines, and a desire to prevent a recurrence of preventable
      infectious diseases resulting from a fear-driven cessation of vaccine
      administration. The objectives of this article are to present a basic review of
      immunology as related to vaccines, to discuss general guidelines for pediatric
      vaccines in canine and feline patients,and to offer suggestions as to how we can
      most positively influence our patients' health from the first visit.

PMID- 16564417
TI  - Pediatric abdominal ultrasonography.
AB  - Pediatric patients are commonly presented to the veterinarian because of signs
      referable to the abdominal cavity caused by congenital anomalies,dietary
      indiscretion, parasitic infestation, and infectious disease. Abdominal ultrasound
      provides valuable clinical information about the peritoneal cavity, great
      vessels, abdominal viscera, and lymph nodes,which is obtained in a noninvasive
      fashion and usually does not necessitate sedation or anesthesia. Ultrasonography
      thus greatly facilitates diagnostic evaluation of the pediatric patient.
      Ultrasound equipment already in place in many small animal veterinary clinics is
      appropriate for most pediatric cases.

PMID- 16564418
TI  - The signalling contributions of Constantin von Economo to basic, clinical and
      evolutionary neuroscience.
AB  - The study, and the companion article that follows, reviews the entire spectrum of
      the epoch-making contributions of Constantin von Economo (1876-1931) to basic,
      clinical and evolutionary Neuroscience. An astute observer and avid writer, von
      Economo left marks of brilliance on fundamental areas of brain research through
      an exuberant record of publications dating from 1899 to 1932. His ingenious
      medical career began with the histological study of the developing pigeon and
      chick hypophysis, and culminated with bold propositions about the neuroanatomy of
      talent and the future evolution of the human brain. On the way, he made the
      seminal discovery of encephalitis lethargica ('von Economo disease'), and
      produced, with Georg N. Koskinas (1885-1975), one of the masterpieces of brain
      science, the 1925 Cytoarchitectonics of the Adult Human Cerebral Cortex, defining
      107 cortical areas on the basis of cytoarchitectonic criteria. His untimely death
      at age 55, barely 5.5 months after inaugurating his new Brain Research Institute
      in Vienna, deprived the Neuroscience world of one of its brightest protagonists
      during the 20th century. An annotated total of 139 scientific works by von
      Economo have been identified. The present study covers the 76 works on brain
      structure, evolution and intelligence, and general works on nervous and mental
      pathology, with the complete bibliographic information. The companion article
      covers the remaining 63 works on encephalitis lethargica and sleep regulation.

PMID- 16564419
TI  - The percipient observations of Constantin von Economo on encephalitis lethargica
      and sleep disruption and their lasting impact on contemporary sleep research.
AB  - The study, and the preceding companion article, reviews the pioneering
      contributions of Constantin von Economo (1876-1931) to Neuroscience in a modern
      context. The neurological studies of von Economo include the discovery of a new
      nosological entity, encephalitis lethargica, with which his name is forever
      linked ('von Economo disease'). Based on a percipient analysis of pathoanatomical
      material from patients with encephalitis lethargica who manifested with either
      insomnia or somnolence, von Economo deduced the existence of distinct centres in
      the brain for the regulation of sleep and wakefulness. He presented a synthesis
      of his ideas in a series of lectures in New York in 1929 and at the First
      International Neurological Congress held in Berne in 1931. Constantin von Economo
      was nominated three times for the Nobel Prize in Physiology or Medicine for the
      discovery of encephalitis lethargica. As those studies have exerted and continue
      to exert the highest impact among von Economo's publications, the present article
      examines the spectrum of his observations on encephalitis lethargica and the
      cerebral control of sleep, documented in 63 published works--including post
      humous translations into French and English of original German texts; complete
      bibliographic information is given. His remaining 76 works of an annotated total
      of 139 scientific publications deal with brain structure, evolution and
      intelligence, as well as general works on nervous and mental pathology and form
      the focus of the preceding article.

PMID- 16564420
TI  - Central nervous changes in social dysfunction: autism, aggression, and
      psychopathy.
AB  - Neurodevelopmental disorders such as autism and schizophrenia involve social
      interaction problems and poor mentalizing abilities, associated with abnormal
      regional cerebral activity. Similar problems may be present in aggressive
      personality disorders and psychopathy. This paper reviews brain imaging data from
      research aiming at establishing possible central nervous correlates to aggression
      and psychopathy. Studies in this field are associated with a range of method
      problems. Differences between criminal offenders and controls may be confounded
      by a number of factors unrelated to personality traits or aggression per se.
      Phenotypical characterisation varies between studies as do the laboratory methods
      and their interpretation. In spite of these problems, there are some recurrent
      findings in the present literature. Hypoactivity or structural reduction of the
      prefrontal cortex is a consistent finding in violent offenders or subjects with
      antisocial personality disorder. When defined as a personality disorder of social
      interaction and empathy, psychopathy seems to be associated rather with central
      abnormalities in the limbic circuitry. Indications of an increased dopaminergic
      neurotransmission relative to the serotonergic have also been connected to such
      personality traits, especially to the AD/HD-related behavioural aspects. Further
      studies using strict phenotypical definitions or experimental models are clearly
      warranted to establish a pathophysiological background to destructive personality
      traits and the propensity to violent acting out.

PMID- 16564421
TI  - Differential expression of NK1 and GABAB receptors in spinal neurones projecting
      to antinociceptive or pronociceptive medullary centres.
AB  - The balance between excitatory and inhibitory input exerted upon spinal cord
      neurones that belong to spinofugal pathways determines the ultimate type of
      information transmitted to the brain. We compared the relative expression of NK1
      and GABAB receptors in two spinomedullary pathways targeting an antinociceptive
      area and a pronociceptive centre, respectively, the lateral part of the caudal
      ventrolateral medulla (VLMlat) and the dorsal reticular nucleus (DRt). Spinal
      cord sections of rats injected in the VLMlat or DRt with the retrograde tracer
      cholera toxin subunit B were triple-immunoreacted for the tracer, NK1 receptors
      and GABAB receptors. The dorsal horn neurones labelled from the VLMlat mainly co
      localized the two receptors while those labelled from the DRt mainly expressed
      GABAB receptors, which was particularly evident in neurones of laminae IV-V. The
      morphological classification of lamina I neurones projecting to the VLMlat showed
      that fusiform, flattened and pyramidal cells mainly co-localized NK1 and GABAB
      receptors. As to lamina I neurones projecting to the DRt, multipolar neurones
      mainly expressed GABAB receptors while the majority of flattened and pyramidal
      neurones co-localized NK1 and GABAB receptors. The present results suggest that
      the expression of NK1 and GABAB receptors varies in neurones participating to
      different spinofugal pathways. The importance of the present findings in the
      knowledge of the endogenous supraspinal pain control system is discussed.

PMID- 16564422
TI  - Regulation of the content of progesterone and estrogen receptors, and their
      cofactors SRC-1 and SMRT by the 26S proteasome in the rat brain during the
      estrous cycle.
AB  - In this work we have determined the role of the 26S proteasome in the regulation
      of the content of progesterone receptors (PR-A and PR-B), estrogen receptors (ER
      alpha and ER-beta), the coactivator SRC-1 and the corepressor SMRT in the rat
      brain during the estrous cycle. The 26S proteasome inhibitor MG132 was injected
      once into the lateral ventricle on proestrous day; and 24h later, on estrous day
      we evaluated the content of PR and ER isoforms, SRC-1 and SMRT in the
      hypothalamus, the preoptic area and the hippocampus by Western blot. A
      significant increase in the content of both PR isoforms, ER-beta and SRC-1 was
      observed after the administration of MG132 in the three studied cerebral regions.
      SMRT content was increased in the hypothalamus and the preoptic area and a
      significant increase in ER-alpha content was only observed in the preoptic area.
      These results suggest that essential proteins that participate in progesterone
      and estrogen actions in the brain should be regulated by the 26S proteasome in a
      tissue-specific manner in physiological conditions.

PMID- 16564423
TI  - Gender and risk factor dependence of cerebral blood flow velocity in Chinese
      adults.
AB  - BACKGROUND AND PURPOSE: The objective of this study is to determine if and how
      cerebral blood flow velocity and stroke risk factors are related in a stroke free
      population. METHODS: This cross-sectional study recruited 1323 stroke-free
      subjects, aged 42-73 years, from a county region in China. Systolic blood flow
      velocities in cerebral arteries were detected with trans-cranial Doppler. Key
      factors, such as anthropometry, life-style, medication use, blood pressure and
      blood biochemical analysis were investigated at the same time. RESULTS: In women,
      even controlled for major cardiovascular risk factors, cerebral blood flow
      velocities of common carotid artery, internal carotid artery, middle cerebral
      artery, anterior cerebral artery and posterior cerebral arteries decreased
      significantly with age (from 43.8 to 39.3, 48.0 to 42.6, 97.7 to 82.8, 79.2 to
      69.4 and 44.1 to 39.7 cm/s in the range of 42-73 years old, p < 0.01 for each).
      In men, however, this inverse trend only existed in common carotid artery (from
      45.6 to 41.7 cm/s, p < 0.01). Multivariate regression showed that most
      established cardiovascular risk factors (e.g. hypertension, hypercholesterolemia,
      diabetes mellitus and overweight/obesity) were associated with decreased blood
      flow velocity in the extra-cranial arteries. However, this association was not
      present (e.g. diabetes and overweight/obesity) or was inversed (e.g. hypertension
      and hypercholesterolemia) in the intra-cranial arteries. CONCLUSION: Extra
      cranial blood flow velocity is significantly and inversely related to age and
      cardiovascular risk factors. The relationship between intra-cranial blood flow
      and risk factors changes and may depend on gender. These finding may have
      importance in the determination of mechanisms of stroke.

PMID- 16564424
TI  - Effect of sporting activity practice on susceptibility to motion sickness.
AB  - The theory of visuo-vestibular conflict is the most commonly accepted to explain
      motion sickness. Visual, vestibular and proprioceptive afferences are involved in
      balance control and this function can be improved by physical and sporting
      activities (PSA). The purpose of the present survey was to investigate the
      relationships between motion sickness susceptibility (MSS) in adulthood and PSA,
      and especially proprioceptive PSA. A questionnaire concerning MSS and PSA was
      filled in by 1829 students (22.3+/-3.4 years of age, 799 males). Subjects having
      practised a sport before the age of 18 have less MSS than the other subjects
      (P<0.001). It should be noted that subjects who practised proprioceptive PSA
      before the age of 18 have less MSS than subjects who practised bioenergetic PSA
      before this age. By practising PSA, subjects are less dependent on visual input
      and use vestibular afferences better. A process of habituation can be involved in
      better managing conflicting sensory afferences reducing susceptibility to motion
      sickness. The practice of proprioceptive PSA develops the proprioceptive
      afferences and improves their treatment by the central nervous system. This
      additional appropriate input associated with an increase in vestibular weight
      compared to vision helps overcome visuo-vestibular conflict.

PMID- 16564425
TI  - Dual-tasking postural control: aging and the effects of cognitive demand in
      conjunction with focus of attention.
AB  - Postural control in everyday life is generally accompanied by posture-unrelated
      cognitive activity. Thus, mild forms of dual-tasking postural control are the
      norm rather than the exception. Based on this consideration and available
      evidence, we propose and empirically examined, in young and old adults, a non
      monotonic, U-shaped relation between the efficacy of postural control and
      concurrent cognitive demands that reflect opposing trends of the effects of
      attention focus and attentional resource competition. When instructed to perform
      an easy cognitive task that presumably shifted the focus of attention away from
      posture control, the center of body pressure (COP) excursions decreased both in
      young and older adults relative to a single-task baseline where the focus of
      attention was explicitly directed towards the postural control task itself.
      However, when performing more demanding cognitive tasks, older adults showed
      increased COP displacements, in line with the predicted U-shape function, whereas
      young adults did not. We outline mechanisms linking postural control to cognitive
      demand and suggest routes for future investigation.

PMID- 16564426
TI  - Normal sensitivity to excitotoxicity in a transgenic Huntington's disease rat.
AB  - Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a
      CAG repeat expansion in the HD gene. Excitotoxic cell damage by excessive
      stimulation of glutamate receptors has been hypothesized to contribute to the
      pathogenesis of HD. Transgenic mouse models of HD have shown variable sensitivity
      to excitotoxicity. The models differ in the genetic background, the type and
      length of the promoter driving the transgene expression, the CAG repeat length
      and/or the HD gene construct length. Furthermore, one has to differentiate
      whether transgenic or knock-in models have been used. All these factors may be
      involved in determining the responsiveness to an excitotoxic insult. Here, we
      explored the responsiveness to excitotoxic damage using a transgenic HD rat model
      carrying 22% of the rat HD gene which is driven by the rat HD promoter and which
      harbors 51 CAG repeats. 3 and 18 months old transgenic HD rats and their wild
      type littermates received unilateral intrastriatal injections of the glutamate
      analogue quinolinic acid. Lesion size was assessed 7 days later using the
      degenerative stain Fluoro-Jade and by immunohistochemistry for the neuronal
      protein NeuN. No difference in susceptibility to excitotoxicity was found between
      the groups. Our study supports mouse data showing maintained susceptibility to
      excitotoxicity with the expression of around 25% of the full HD gene. Differences
      in sensitivity to excitotoxicity between genetic animal models of HD may be
      dependent on the length of the expressed HD gene although additional factors are
      also likely to be important.

PMID- 16564427
TI  - Exposure of mothers to diphenyl ditelluride during the suckling period changes
      behavioral tendencies in their offspring.
AB  - The long-lasting possible influence of maternal exposure to 0.03 mg/kg of
      diphenyl ditelluride during the first 14 days of lactational period on later
      offspring behavior was examined in Wistar rats. Open-field locomotor activity,
      spontaneous alternation in the T-maze, behavior in the elevated plus-maze, motor
      coordination in the coat-hanger and rotorod tasks were evaluated in 30 day old
      pups. There were no significant specific overt signs of maternal intoxication.
      There were a small (less than 5%) but significant transitory differences in the
      body weight gain of pups between exposed and control groups, which were apparent
      from day 30 of suckling. Locomotor activity in the open-field task was similar
      between telluride and control groups. In the coat-hanger test, the latency before
      falling for the tellurium group was higher than that of the control group.
      However, the behavior of both groups was similar in the rotorod test and
      spontaneous alternation in the T-maze. Tellurium-treated pups presented a higher
      number of entries and spent more time in the open arms of the elevated plus-maze
      than control pups. The behavioral alterations observed here after tellurium
      exposure can be cautiously interpreted as an indication of behavioral
      disinhibition. In conclusion, this study demonstrated that dam exposure to
      diphenyl ditelluride can cause subtle behavioral changes in the offspring, which
      can be related to neurotoxic effects of diphenyl ditelluride.

PMID- 16564428
TI  - Effects of group I metabotropic glutamate receptors blockade in experimental
      models of Parkinson's disease.
AB  - The present study was devoted to investigate the effects of the metabotropic
      glutamate receptor(mGluR)5 antagonist [(2-methyl-1,3-thiazol-4
      yl)ethynyl]pyridine (MTEP) and the mGluR1 antagonist, (3-ethyl-2-methyl-quinolin
      6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM), in animal
      studies indicative of antiparkinsonian-like activity such as haloperidol-induced
      catalepsy, hypoactivity in open field following haloperidol, and rotation in rats
      with unilateral 6-hydroxydopamine(OHDA)-induced lesions of the midbrain
      dopaminergic system (alone and in combination with L-DOPA). Moreover,
      antidyskinetic activity of different mGluR ligands was evaluated in the rat model
      of L-DOPA-induced dyskinesia. Both MTEP (5 mg/kg) and EMQMCM (4 mg/kg) slightly
      inhibited haloperidol (0.5 mg/kg)-induced catalepsy. However, neither substance
      reversed the hypoactivity produced by haloperidol (0.2 mg/kg). Although MTEP did
      not produce significant turning, it inhibited contralateral rotations after L
      DOPA (at 5 mg/kg) and alleviated L-DOPA-induced dyskinesia (at 2.5 and 5 mg/kg)
      in 6-OHDA-lesioned rats. In contrast, mGluR1 antagonists EMQMCM and RS-1
      aminoindan-1,5-dicarboxylic acid (AIDA) failed to modify L-DOPA-induced
      dyskinesia. The results of the present study suggest that either subtype of group
      I of mGluRs may be involved in the pathologically altered circuitry in the basal
      ganglia. However, the equivocal results do not strongly support the hypothesis
      that mGluR1 and mGluR5 antagonists may be beneficial in the symptomatic treatment
      of Parkinson's disease. However, mGluR5 antagonists may prove useful for the
      symptomatic treatment of L-DOPA-induced dyskinesia.

PMID- 16564429
TI  - Genetic investigation of methylenetetrahydrofolate reductase (MTHFR) and catechol
      O-methyl transferase (COMT) in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic neurological disease characterized by
      central nervous system (CNS) inflammation and demyelination. The C677T
      substitution variant in the methylenetetrahydrofolate reductase (MTHFR) gene has
      been associated with increased levels of circulating homocysteine and is a mild
      risk factor for vascular disease. Higher blood levels of homocysteine have also
      been reported in MS. Thus, the C677T mutation of the MTHFR gene may influence MS
      susceptibility. Noradrenaline, a neurotransmitter believed to play an
      immunosupressive role in neuroinflammatory disorders, is catabolized by catechol
      O-methyl transferase (COMT). The COMT G158A substitution results in a three- to
      four-fold decreased activity of the COMT enzyme, which may influence CNS synaptic
      catecholamine breakdown and could also play a role in MS inflammation. We tested
      DNA from Australian MS patients and unaffected control subjects, matched for
      gender, age and ethnicity. Specifically, we genotyped the MTHFR C677T and the
      COMT G158A mutations. Genotype distributions showed that the homozygous mutant
      MTHFR genotype (T/T) and the COMT (H/H) genotype were slightly over-represented
      in the MS group (16% versus 11% and 24% versus 19%, respectively), but both
      variations failed to reach statistical significance (P=0.15 and P=0.32,
      respectively). Hence, results from the present study do not support a major role
      for either functional gene mutation in MS susceptibility.

PMID- 16564430
TI  - Sleep deprivation abolishes the locomotor stimulant effect of ethanol in mice.
AB  - The present study aimed to investigate the effects of sleep deprivation (SD) on
      the dose-dependent stimulant effect of ethanol (ETOH) on the open-field behavior
      of female and male mice. Sleep-deprived (48 h, multiple platforms method) or home
      cage control female mice were treated with saline (SAL) or 1.4, 1.8 or 2.2g/kg
      ETOH 5 min before behavioral testing. ETOH produced a dose-dependent increase in
      open-field locomotor behavior. This locomotor stimulant effect did not reflect a
      general stimulation in motor activity, since it was accompanied by a simultaneous
      decrease in rearing frequency as well as by no modification in immobility
      duration. The effects of ETOH on these three behavioral parameters were
      specifically modified by SD: the locomotor stimulant effect was abolished, the
      rearing inhibitory effect was potentiated and the lack of effect on immobility
      was changed to increase in immobility. Similar results were obtained for male
      mice although the effects of SD had a lower magnitude. The present findings
      demonstrate that the acute effect of ETOH on mice's motor activity are
      behaviorally complex and can be specifically modulated by SD.

PMID- 16564431
TI  - Dose-response characteristics of ketamine effect on locomotion, cognitive
      function and central neuronal activity.
AB  - The present dose-response study sought to determine the effects of subanesthetic
      dosages (4-16 mg/kg) of ketamine on locomotion, sensorimotor gating (PPI),
      working memory, as well as c-fos expression in various limbic regions implicated
      in the pathogenesis of schizophrenia. In addition, we examined whether ketamine
      induced locomotion was influenced by the dark/light cycle. We found that ketamine
      increased locomotor activity in a dose dependent manner, but found no influence
      of the dark-light cycle. Additionally, ketamine dose-dependently interrupted PPI,
      resulting in prepulse facilitation at doses of 8 and 12 mg/kg. The dose of 12
      mg/kg also induced impairments in working memory assessed by the discrete-trial
      delayed-alternation task. C-fos expression indicated that the dose-dependent
      behavioral effects of ketamine might be related to changes in the activity of
      limbic regions, notably hippocampus and amygdala.

PMID- 16564432
TI  - Discomfort intolerance: Development of a construct and measure relevant to panic
      disorder.
AB  - The construct of discomfort intolerance (proposed as an individual difference in
      the ability to tolerate uncomfortable sensations) is introduced and psychometric
      properties of a measure of this trait are provided. The Discomfort Intolerance
      Scale (DIS), a self-report measure of discomfort intolerance, was evaluated using
      a variety of samples (total N approximately 1700), including patients with panic
      disorder, clinical controls, and nonclinical community members. Factor analyses
      suggest the DIS contains two factors, including a factor indexing the ability to
      tolerate discomfort and pain (Factor 1: alpha = .91), and a factor, which appears
      to measure avoidance of physical discomfort (Factor 2: alpha = .72). Cross-time
      reliability shows good stability across 12 weeks (Factor 1 = .63, Factor 2 =
      .66). Convergent and discriminant validity coefficients indicated that the DIS
      performed as expected against established measures of psychopathology. The DIS
      appears to be a sound measure of a broad individual difference variable tapping
      the ability to tolerate a variety of uncomfortable sensations and may be relevant
      to the pathogenesis of anxiety disorders.

PMID- 16564433
TI  - Anxiety sensitivity among Cambodian refugees with panic disorder: A factor
      analytic investigation.
AB  - Among Cambodian refugees with panic disorder (N = 208), we performed two factor
      analyses, one with the ASI, another with an Augmented ASI (consisting of the 16
      item ASI supplemented with a 9-item addendum that assesses additional Cambodian
      concerns about anxiety-related sensations). The principal component analysis of
      the ASI yielded a 3-factor solution (I, "Weak Heart Concerns"; II, "Social
      Concerns"; III, "Control Concerns"); the Augmented ASI, a 4-factor solution: I,
      "Wind Attack Concerns"; II, "Weak Heart Concerns"; III, "Social Concerns"; and
      IV, "Control Concerns." The item clustering within the factor solution of both
      the ASI and Augmented ASI illustrates the role of cultural syndromes in
      generating fear of mental and bodily events.

PMID- 16564434
TI  - Is "shy bladder syndrome" (paruresis) correctly classified as social phobia?
AB  - Paruresis manifests in an inability to urinate in public restrooms followed by a
      considerable avoidance behavior. According to DSM-IV TR this disorder is
      classified as social phobia. A sample of N = 226 subjects completed different
      questionnaires concerning paruresis, social phobic symptoms, lower urinary tract
      symptoms and depressive symptoms. These individuals were divided into four
      groups: no symptoms, suffering primarily from paruresis, non-generalized social
      phobia and generalized social phobia. The paruretic group differs significantly
      in all symptom variables from both the non-generalized and the generalized social
      phobia groups. Regression analysis separated by groups shows that the
      interference with everyday life can be mainly explained by paruretic symptoms (in
      the paruretic group) or by social anxiety and depressive symptoms, respectively
      (in the social phobic groups). These results question the classification of
      paruresis as simply being a form of social phobia.

PMID- 16564435
TI  - What are the roles of perfectionism and responsibility in checking and cleaning
      compulsions?
AB  - Empirical findings revealed that an inflated sense of responsibility has a major
      impact on obsessive-compulsive symptomatology (OCS). Another cognitive variable,
      perfectionism, is also theoretically linked to OCS. The assumption about the
      insufficient but necessary role of perfectionism for OCS and the view of
      perfectionism as a manifestation of avoidance of serious consequences led us to
      explore the role of an important cognitive mediator (responsibility) in this
      relationship. The present study aimed to explore the mediational role of
      responsibility for the effects of perfectionism on checking and cleaning symptom
      profiles of OCS in a nonclinical population in Turkey. Findings of the present
      study suggested that responsibility appraisals mediate effects of self-oriented
      and socially prescribed perfectionism on checking and the effect of socially
      prescribed perfectionism on cleaning. There was a partial mediation for self
      oriented perfectionism on cleaning. The findings are discussed within the scope
      of current literature and implications for clinical applications are suggested.

PMID- 16564436
TI  - Changes in intrusive memories associated with imaginal reliving in posttraumatic
      stress disorder.
AB  - The study investigated changes in intrusive memories associated with imaginal
      reliving of traumatic events in posttraumatic stress disorder (PTSD). The study
      population comprised 44 patients treated with imaginal reliving in the context of
      cognitive therapy for PTSD [Behav. Res. Ther. 38 (2000) 319-345]. For most
      patients, imaginal reliving did not lead to exacerbations in intrusion frequency.
      The decrease in intrusion frequency after reliving was gradual, as was the
      decrease in their distress, vividness, and perceived "nowness." Poorer outcome,
      i.e., a smaller reduction in residual gain scores for intrusion frequency with
      reliving, was associated with greater initial PTSD severity, greater anger,
      greater perceived "nowness" of intrusive memories, and more negative
      interpretations of PTSD symptoms. The patient's anxiety, depression, self-blame,
      and dissociation were not predictive of response to reliving.

PMID- 16564437
TI  - Maternal panic disorder: Infant prematurity and low birth weight.
AB  - The aim of this pilot research was to investigate whether infants of mothers with
      panic disorder (PD) would be at higher risk for prematurity and low birth weight
      (corrected for gestational age) than controls. Medical records were reviewed for
      25 mothers with PD and 33 mothers without a lifetime history of anxiety disorders
      or other major psychopathology as determined by diagnostic interview. Mothers
      also completed questionnaires concerning demographic information and life
      stresses. Compared to controls, infants with PD mothers were not significantly
      more likely to be born prematurely or earlier than controls but did show smaller
      birth weight corrected for gestational age, even after accounting for possible
      confounding influences. Additional research is needed to confirm these
      preliminary findings. Studying PD mothers during pregnancy could provide insight
      concerning mechanisms for the development of low birth weight and
      psychopathology.

PMID- 16564438
TI  - Delays in referral of patients with social phobia, panic disorder and generalized
      anxiety disorder attending a specialist anxiety clinic.
AB  - Individuals with anxiety disorders experience substantial delays in obtaining
      treatment, but little is known about whether people with specific anxiety
      subcategories are differentially affected. The present study used a modified
      Encounter Form to examine the cause and length of delays in reaching primary care
      and specialist services amongst patients with panic disorder (PD/PD-Ag), social
      phobia (SP), and generalized anxiety disorder (GAD). Participants were 142
      consecutive patients attending a specialist anxiety clinic in South Western
      Sydney. On average, participants with SP took much longer to consult a primary
      health care provider. Primary care assessments of those with SP often failed to
      detect anxiety as the key problem, and subsequently, those with SP reported
      longer delays in reaching specialist care (>9 years). It is not possible to
      extrapolate the findings to all individuals with SP, as the study was based on
      specialist service attenders. Nevertheless, the data supports previous findings
      in suggesting that SP may not be well-recognized as a disorder needing treatment,
      either by the patient or the primary health care provider. Appropriate
      educational programs seem warranted to ensure appropriate treatment for this
      condition.

PMID- 16564439
TI  - Health complaints in acknowledged and unacknowledged rape victims.
AB  - Rape may have physical as well as mental health consequences. Previous studies on
      health complaints in sexual assault survivors have focused on women who
      acknowledged their assault as rape. Unacknowledged rape victims do not define
      their assault as "rape" despite meeting legal definitions. In this study,
      acknowledged victims, unacknowledged victims, and a control group reported the
      number of health complaints, the intensity of complaints, and how often they
      reported these complaints to health professionals. Rape alone, without
      acknowledgment, was associated with in an increase in the reported number and
      intensity of health complaints and the frequency at which these complaints are
      addressed to health professionals. Acknowledgment of rape was associated with an
      even greater increase in the number and intensity of health complaints.

PMID- 16564440
TI  - Interpersonal correlates of generalized anxiety disorder: Self versus other
      perception.
AB  - The present investigation examined the interpersonal functioning of undergraduate
      students who met self-report criteria for generalized anxiety disorder (GAD),
      both as they perceive it and as perceived by their self-nominated friends. Forty
      eight participants who met self-report criteria for GAD endorsed greater global
      severity of interpersonal problems on the 64-item version of the Inventory of
      Interpersonal Problems [Horowitz, L. M., Alden, L. E., Wiggins, J. S., Pincus, A.
      L. (2000). Inventory of Interpersonal Problems: Manual. San Antonio, TX: The
      Psychological Corporation] than 53 control participants. However, friends of GAD
      participants did not attribute significantly greater interpersonal problems to
      them than did friends of control participants. GAD participants reported less
      secure attachment to their parents than control participants but reported similar
      levels of attachment to peers and perceived social support. Furthermore, there
      were no significant differences between the friends of the GAD participants and
      friends of the control participants on ratings of their friendships quality.
      Findings are discussed in the context of their relevance to the etiology,
      maintenance, and treatment of GAD.

PMID- 16564442
TI  - Stereotactic body radiation therapy for extracranial oligometastases: does the
      sword have a double edge?
AB  - Understanding the acute and chronic toxicities of stereotactic body radiation
      therapy (SBRT) for extracranial oligometastases might reveal treatment parameters
      that can be modulated to enhance the therapeutic ratio. Therefore, we searched
      PubMed from 1995 to 2005 for reports on stereotactic body radiation therapy, with
      emphasis on treatment of metastatic lesions of the lung and/or liver. Reports of
      SBRT for primary tumors of these sites were included to increase the number of
      evaluable patients. The reports were categorized by organ system and evaluated
      based on number of patients, number of lesions treated, dose fractionation
      scheme, and local control. A total of 15 lung studies (including 683 patients)
      and 7 liver studies (including 156 patients) were identified. Overall grade 3 to
      5 toxicity was seen in up to 15% of patients in the lung SBRT studies and up to
      18% of patients in the liver SBRT studies. Only 3 deaths were reported after SBRT
      of the liver and 2 after SBRT of the lung for treatment related mortality rates
      of 2% and 0.3%, respectively. No definitive relationship was found between
      radiation dose and toxicity. Conversely, radiation treatment volume may be
      associated with the infrequent toxicities that occur. The literature supports
      SBRT as a safe and effective treatment for oligometastases of the liver and lung.
      Further studies are needed to define the optimal dose and fractionation schedule.

PMID- 16564443
TI  - Extracranial radiosurgery (stereotactic body radiation therapy) for
      oligometastases.
AB  - Extracranial radiosurgery, also known as stereotactic body radiation therapy
      (SBRT), is an increasingly used method of treatment of limited cancer metastases
      located in a variety of organs/sites including the spine, lungs, liver, and other
      areas in the abdomen and pelvis. The techniques used to perform SBRT were
      initially modeled after intracranial radiosurgery, although considerable
      evolution in technique and conduct has occurred for extracranial applications.
      Unlike intracranial radiosurgery, SBRT requires characterization and accounting
      for inherent organ movement including breathing motion. Potent dose
      hypofractionation schedules have been used with SBRT such that the treatment is
      generally both ablative and convenient. Because the treatment is severely
      damaging to tissues within and about the target, the volume of adjacent normal
      tissue must be strictly minimized to avoid toxic late effects. Outcomes in
      various sites show very high rates of local control with toxicity mostly related
      to tubular tissues like the airways and bowels. With proper conduct though, SBRT
      can be an extremely effective treatment option for oligometastases.

PMID- 16564444
TI  - Physics and imaging for targeting of oligometastases.
AB  - Oligometastases refer to metastases that are limited in number and location and
      are amenable to regional treatment. The majority of these metastases appear in
      the brain, lung, liver, and bone. Although the focus of interest in the past
      within radiation oncology has been on the treatment of intracranial metastases,
      there has been growing interest in extracranial sites such as the liver and lung.
      This is largely because of the rapid development of targeting techniques for
      oligometastases such as intensity-modulated and image-guided radiation therapy,
      which has made it possible to deliver single or a few fractions of high-dose
      radiation treatments, highly conformal to the target. The clinical decision to
      use radiation to treat oligometastases is based on both radiobiological and
      physics considerations. The radiobiological considerations involve improvement of
      treatment schema for time, dose, and volume. Areas of interests are
      hypofractionation, tumor and normal tissue tolerance, and hypoxia. The physics
      considerations for oligometastases treatment are focused mainly on ensuring
      treatment accuracy and precision. This article discusses the physics and imaging
      aspects involved in each step of the radiation treatment process for
      oligometastases, including target definition, treatment simulation, treatment
      planning, pretreatment target localization, radiation delivery, treatment
      verification, and treatment evaluation.

PMID- 16564445
TI  - Molecular correlates of site-specific metastasis.
AB  - Metastasis is the spread of tumor cells from a primary site to distant organs. It
      is the major cause of cancer morbidity and death. In the last few decades,
      significant advances have been made in surgical techniques, radiation therapy
      delivery, and chemotherapy including the development of combination regimens and
      agents inhibiting newly characterized biological targets. Treatment of
      metastasis, however, remains the most challenging task in cancer therapy because
      metastatic growth relies on complex interactions between tumor cells and the host
      and is often resistant to all therapeutic modalities. Management of metastasis in
      bone is especially challenging given the difficulty of access for therapeutic
      agents. Contemporary research seeks to explain the striking organ specificity
      observed in metastasis. In this article, we will examine historic perspectives on
      site-specific metastasis and review cellular and molecular evidence pertinent to
      the mechanisms of organ specificity. We will discuss a number of studies that aim
      to identify gene signatures correlating with organ-selective metastasis using
      microarray technology. Lastly, we will discuss potential areas of future research
      including microRNAs, proteomics, and the development of diagnostic and
      therapeutic interventions.

PMID- 16564446
TI  - Modeling growth kinetics and statistical distribution of oligometastases.
AB  - The kinetics of development of micrometastases, and especially of small numbers
      of metastases (oligometastases), was explored by using simple assumptions to
      develop concepts that may be useful for framing future research. The conclusions
      depend on the assumptions and hence must be considered speculative. It is assumed
      that beyond a threshold size for initiation of metastatic spread, which varies
      widely from tumor to tumor, the rate at which a primary tumor sheds new
      metastases increases exponentially, in parallel with its exponential growth. This
      increasing rate of release of new metastatic clonogens from the primary tumor is
      accompanied by a similar exponential growth of each of the micrometastases newly
      established at a secondary site. This creates a log-log linear relationship
      between the volume distribution of metastases and number of metastases, there
      being one largest metastasis followed by an exponentially expanding number of
      logarithmically smaller micrometastases. For example, if the micrometastases and
      the primary tumor grew at the same rate for 6 doublings after initiation of the
      first metastasis, then the primary tumor would have increased its volume by a
      factor of 64 (2(6)) and would be shedding metastatic clonogens at 64 times the
      initial rate. The first metastasis would undergo 6 doublings and contain 64
      cells; the succeeding 2 metastases, released as the primary doubled in volume,
      would undergo 5 doublings and each would contain 32 cells; and so forth down to
      the 64 most recently developed single-cell metastases. However, the growth rate
      of metastases is expected to be faster than that of the primary tumor so that the
      rate of increase in volume of the micrometastases would be faster than the rate
      of increase in their numbers (through release of new metastases from the
      primary). Thus, although the log-log linear relationship is maintained, the slope
      of the volume frequency curve is changed; if the micrometastases grew 5 times
      faster than the primary, the slope would change by a factor of 5. Removal of the
      primary tumor as a source of new metastases truncates the expansion in numbers of
      metastases without affecting the growth rate of existing micrometastases, with
      the result that the volume-frequency relationship is maintained but the whole
      curve is shifted to larger volumes as micrometastases grow toward clinical
      detectability. The development of an oligometastatic distribution requires that
      the exponential expansion in the number of new metastases be stopped by
      eliminating the primary tumor soon after the first metastasis is shed. A cell
      destined to become part of an oligometastatic distribution had just been newly
      deposited at its metastatic site at the time the primary tumor was removed and
      must undergo about 30 doublings to become clinically detectable as an overt
      metastasis (2(30) or 10(9) cells). Thus, the time interval between removal of the
      primary and subsequent appearance of oligometastases will be toward the upper end
      of a distribution of "metastasis-free" intervals for its particular class of
      tumor. The actual time to appearance of a solitary metastasis, or of
      oligometastases, in any particular patient will depend on the growth rate of the
      metastases in that individual but will always require about 30 volume doublings.
      An apparently solitary metastasis appearing synchronously with the primary tumor
      is unlikely to be solitary because, to do so, it would have to have undergone
      about 30 doublings without further release of metastatic clonogens from the
      primary that is, in our model, within 1 doubling in volume of the primary tumor.
      For the same reason, a synchronous or early appearing oligometastatic
      distribution is unlikely, but if it were to exist, there would be a steep
      gradient between the volumes of largest and smallest metastases because the
      growth rate of the micrometastases to produce synchronous metastases, without
      having further metastases shed from the primary, would have to be fast (up to
      30x) relative to the growth rate of the primary. Conversely, a steep gradient in
      volumes of successive echelons of metastases reflects fast growth of metastases
      relative to the primary and favors the possibility of an oligometastatic
      distribution. This ratio of growth rates of metastases to primary is defined by
      the slope of the log-log curve for the volume-frequency distribution of
      metastases, which, in clinical practice, is difficult to determine over a wide
      range and is, by definition, essentially impossible for oligometastases. However,
      the volume-frequency relationship, measured over a wide range, is the same as the
      ratio of the volume of the largest to second-largest metastases in an
      oligometastatic situation. For example, if the metastasis doubled 5 times faster
      than the primary, the largest metastasis would be larger by 5 doublings than its
      closest follower(s), that is, by a factor of 2(5) or 32, equivalent to a 3.2-fold
      difference in diameter if the metastases were spherical. Alternatively, if an
      initially solitary and measurable metastasis is subsequently joined by measurable
      followers, the number of volume doublings separating successive echelons in the
      series can be determined directly, and the larger the difference (measured in
      doublings), the greater the probability that there will be a limited,
      oligometastatic condition (ie, in clinical terms, subsequent metastases will stop
      appearing after the large leader metastasis and a short succession of followers
      have been removed at 1 or more operations). In summary, the probability of there
      being an oligometastatic distribution is increased as the interval between
      removal of the primary tumor and appearance of metastases lengthens. It is also
      more likely the faster the metastases are growing relative to the growth rate of
      the primary tumor before its removal. Effective systemic cytotoxic treatment (eg,
      chemotherapy, hormonal manipulation, biological agents) given in the
      perioperative period, or concomitantly with radiation therapy for the primary
      tumor, would truncate the volume-frequency distribution toward an oligometastatic
      one by eliminating the smallest, most recently formed "tail-ender" metastases.
      That process, which only occurs at the threshold volume of the primary at which
      metastases are first initiated, would not be influenced by whether surgery or
      radiation therapy was chosen to treat the primary tumor, regardless of the
      overall duration of radiation therapy. Chemotherapy adjuvant to surgery is not
      usually indicated in the curative treatment of solitary or oligometastases
      because they represent a truncated distribution with few or no stragglers. If
      subclinical stragglers exist, they would usually be relatively large and, even
      though subclinical, too large to be cured by chemotherapy. Exceptions would be
      early rapidly growing oligometastases, especially from a slowly growing primary,
      or solitary metastases from an unknown primary where second echelon metastases,
      if they exist, may still be small. Otherwise chemotherapy could be postponed and
      used for palliative growth restraint of unusually large and/or numerous
      stragglers.

PMID- 16564447
TI  - Solitary metastases: illusion versus reality.
AB  - "Suddenly a solitary horseman appeared on the horizon, then another, then
      another...in a few moments a whole crowd of horsemen swooped down upon him."
      Leacock The illusion of solitary metastases is counterintuitive but has generated
      a sizable literature on the subject. The reality is that there are more
      metastatic deaths each year than the total number of true long-term survivors of
      solitary metastases combining all organ sites in the literature of the past
      century up to the present time. The largest number of solitary metastases
      survivors had metastases primarily in the lung and/or liver. With innovations in
      molecular imaging and advances in molecular oncology, the stage is set to detect
      truly solitary metastases early. Then, aggressive treatment by surgical excision,
      stereotactic body radiosurgery, targeted chemotherapy, or immunotherapy could
      eradicate the lesion. A comprehensive review of solitary metastases in a large
      variety of anatomic sites is presented. A broader staging system is recommended
      to encompass a solitary metastasis (M1) and oligometastases (M2) as distinct from
      multiple metastases (M3).

PMID- 16564448
TI  - Treatment of oligometastases after successful immunotherapy.
AB  - Local destruction of individual metastases by any of a number of effective
      modalities fails as a treatment for most patients with disseminated cancer
      because of the presence of either undetected micrometastases or simply too many
      lesions. The availability of a systemic therapy that could reduce the number of
      metastases to a manageable few would dramatically increase the utility of
      surgical metastasectomy or other locally ablative measures. Interleukin-2-based
      immunotherapy can serve exactly this function in some patients with renal cancer
      or melanoma. We review the effectiveness of surgery in treating limited relapses
      or residual disease in patients who have responded to systemic immunotherapy.
      These data indicate that a surprising percentage of such patients can enjoy
      durable disease-free survival after surgical removal of their oligometastases,
      and, for a significant minority, it appears to be curative.

PMID- 16564451
TI  - Tibial malunion.
AB  - Tibial malunion, a fracture healed in a position that affects the mechanical
      function of the limb, can be difficult to assess and to correct surgically.
      Precise definition of malunion has yet to be determined, and the limits of
      deformity which are associated with arthritic change also remain imprecise.
      Surgical intervention is therefore primarily indicated in symptomatic patients or
      those with relatively severe deformity. The several described techniques for
      correction of tibial malunion can achieve excellent results, although the surgery
      is not without substantial risk and recovery time. These issues should be
      discussed at length with patients before surgery.

PMID- 16564450
TI  - Tibial nonunion.
AB  - Nonunions of the tibia represent challenging orthopedic problems, which require
      the surgeon to analyze numerous factors and choose an appropriate treatment.
      Tibial nonunion treatment requires establishing its existence and cause. The
      treatment algorithm necessitates consideration of a wide variety of factors: the
      location of the nonunion, the presence or absence of infection, and any angular
      or rotational deformity. Given advances in implant design and biologic agents, a
      wide variety of management options exist for the treatment of tibial nonunions.
      This article reviews surgical treatments for tibial nonunions.

PMID- 16564452
TI  - Ankle syndesmosis injuries.
AB  - Physician awareness of ankle syndesmosis injuries is improving. The anatomy
      involved and the mechanism of injury are extremely relevant for the understanding
      and treatment of this type of injury. Examination under anesthesia may confirm
      the syndesmosis instability. Based on those findings, stabilization is the
      recommended approach.

PMID- 16564453
TI  - Reconstruction of failed ankle fractures.
AB  - Ankle fractures are some of the most common injuries that are treated by
      orthopedic surgeons. Optimal long-term results of ankle fractures require
      accurate reconstruction, a thorough understanding of the mechanism of injury, and
      accurate radiographic assessment. Failure to reduce and maintain fractures and
      dislocations around the ankle properly predisposes to instability and late
      osteoarthritis. This article focuses on the reconstruction of failed ankle
      reconstruction that results in malunion or nonunion. The indications for fusion
      or arthroplasty to treat end-stage degenerative changes are discussed. The
      treatment of concomitant infection and neuropathic fractures are outlined.

PMID- 16564454
TI  - Reconstruction after talar fractures.
AB  - Malunited and nonunited talar fractures cause significant disability. Distinction
      between partial and total avascular necrosis (AVN) determines the choice of
      treatment. Patients who have minimal or no AVN and well-preserved joint cartilage
      may be amenable to corrective osteotomy through the malunited fracture or removal
      of the pseudoarthrosis. Secondary reconstruction with joint preservation leads to
      considerable functional improvement in painful talar malunions and nonunions in
      reliable patients. If symptomatic arthritis is present, arthrodeses and
      correction of deformity through the fusion or with additional osteotomies provide
      predictable results, although they do not restore normal foot function. Fusions
      should be limited to the affected joint. If the subtalar joint shows severe
      arthritic changes, every attempt should be made to salvage the ankle and
      talonavicular joints.

PMID- 16564455
TI  - Post-calcaneus fracture reconstruction.
AB  - This article outlines the pathoanatomy of malunited calcaneal fractures and
      reviews the literature on resulting painful sequelae, diagnostic work-up, as well
      as reconstructive treatment options and their outcome.

PMID- 16564456
TI  - Late reconstruction after navicular fracture.
AB  - The tarsal navicular is the figurative and literal keystone of the medial
      longitudinal arch of the foot. Therefore, injuries to the navicular may have a
      disproportionately profound effect on the overall function of the foot and ankle
      in comparison with its small size. Even optimally treated injuries can go on to
      significant posttraumatic sequelae, and leave the midfoot with chronic deformity,
      arthritis, and loss of motion. This article reviews the posttraumatic sequelae
      that can be seen after navicular fracture and provides an overview of the
      treatment principles and alternatives that are available.

PMID- 16564457
TI  - Management of cuboid crush injuries.
AB  - Cuboid crush injuries are usually seen with forceful plantar flexion and
      abduction injuries of the foot. Shortening of the lateral column and disruption
      of the articular surfaces are often the result, requiring operative
      reconstruction and fixation to prevent subsequent pes planus deformity and
      disability. The indications for and techniques of operative intervention are
      reviewed for acute and late presentation of this injury.

PMID- 16564458
TI  - Treatment of the missed Lisfranc injury.
AB  - Lisfranc joint injuries may be missed at the time of occurrence potentially
      leading to persistent instability, deformity, or arthritis. In the absence of
      significant residual arthritis or fixed deformity, delayed open reduction and
      internal fixation with or without reconstruction of the Lisfranc ligament may be
      performed. An alternative is reduction and primary arthrodesis of the relatively
      immobile medial tarsometatarsal (TMT) joints. In the presence of significant
      residual arthritis or fixed deformity that is recalcitrant to conservative
      treatment, arthrodesis, including correction of deformity, is the treatment of
      choice for the first, second, and third TMT joints. Resection arthroplasty of the
      fourth and fifth TMT joints may be preferable to arthrodesis in order to maintain
      physiologic motion.

PMID- 16564459
TI  - First ray injuries.
AB  - The first ray differs from the other rays in its position and its importance with
      weight bearing. Because it is a critical structure in the formation of the tripod
      of the foot, injuries to this ray can cause critical alterations in the
      biomechanics of the foot. This allows for pathologic weight-bearing points of
      contact and deformity that lead to a disabling gait. Physicians who are involved
      in the care of the foot and ankle should be familiar with the spectrum of
      injuries that concern the first ray. These injuries, their management, and
      sequelae are reviewed.

PMID- 16564460
TI  - Foot and ankle reconstruction after blast injuries.
AB  - Foot and ankle reconstruction following blast trauma is particularly challenging
      based on the devastating soft tissue injuries associated with open comminuted
      fractures. Considering the difficulties encountered in reconstruction, the
      functional limitations associated with many salvaged limbs, and the superior
      performance of contemporary prosthetics, many injured service members may benefit
      more from below knee amputation than from limb salvage. Limb salvage of blast
      injured extremities is a multidisciplinary effort directed toward eradication of
      infection, treatment of soft tissue and bone defects, and management of late
      reconstructive procedures. External ring fixators have an important and expanding
      role in the treatment algorithm.

PMID- 16564461
TI  - Treatment of posttraumatic injuries to the nerves in the foot and ankle.
AB  - Nerve injuries of the foot and ankle can result in pain, numbness, or loss of
      motor function. A thorough history and physical examination are required to
      diagnose the injury correctly and guide treatment. Treatment may involve
      conservative measures, primary nerve repair or nerve grafting, or resection and
      relocation of painful neuroma. Potential complications include the development of
      chronic pain syndromes.

PMID- 16564463
TI  - Reconstruction of the infected traumatized joint.
AB  - This article discusses reconstruction of the infected traumatized joint. In some
      cases the injured joint has posttraumatic arthritic change, and the surgeon is
      challenged with known or potential infection that confounds the treatment plan.
      Failure to treat the associated deep infection adequately results in failure to
      achieve the surgical goals. Ongoing infection can compromise the soft tissue
      envelope significantly by sinus tract formation or inflammation. The local bone
      may be eroded or softened which compromises the reconstructive alternatives.
      Attempted fusion in the face of undiagnosed and untreated infection may cause the
      fusion to fail. All of these issues can result in a below-knee amputation.

PMID- 16564462
TI  - Reconstruction of the foot after leg or foot compartment syndrome.
AB  - Compartment syndrome should be treated early and aggressively to prevent late
      complications. Patients may have late deformity because of a failure of
      diagnosis, inadequate decompression, or a delay in fasciotomies. Late
      reconstruction will allow a plantigrade and relatively functional foot. Complete
      excision of scarred muscle will prevent recurrence in established deformities.
      Early treatment may prevent significant functional impairment by well-placed
      tenotomies. In patients with severe long-term deformities with extensive soft
      tissue contraction, incremental correction may be an appropriate intermediate
      intervention.

PMID- 16564464
TI  - Soft tissue coverage for posttraumatic reconstruction.
AB  - Posttraumatic foot and ankle reconstruction requires careful preoperative
      planning to reduce wound complications. Systemic and local factors need to be
      considered. A careful surgical technique can avoid the need for surgical soft
      tissue coverage. Recognition of the need for coverage preoperatively improves
      outcomes. Often, dressings and time allow minor wound complications to heal. More
      severe wound issues require early soft tissue coverage by local or free flaps to
      prevent failure of the surgery.

PMID- 16564466
TI  - Mental retardation: diagnosis, management, and family support.

PMID- 16564468
TI  - Geriatrics and gerontology education for nurses: the AACN/Hartford partnership.

PMID- 16564469
TI  - Aging is a human experience of courage and human development.

PMID- 16564470
TI  - Introducing baccalaureate student nurses to gerontological nursing.
AB  - The faculty at the University of Missouri-Columbia Sinclair School of Nursing
      (MUSSON) developed and implemented a gerontological nursing care course, with
      support from the Health Resources and Services Administration, the American
      Association of Colleges of Nursing, and the John A. Hartford Foundation. The
      course, with both didactic and clinical components, was mandatory for all
      students in the baccalaureate program. The course drew on two resources unique to
      the MUSSON: Senior Care, the school's home care agency, and TigerPlace, a
      retirement community closely linked to the school. Goals of the course were to
      increase knowledge of gerontology and gerontological nursing and to promote more
      positive student attitudes toward older adults. Evaluation of six semesters of
      pretest and posttest data found that knowledge increased although attitudes
      toward older adults did not become more positive. However, despite the lack of
      quantifiable improvement in attitudes, some students wrote positive comments on
      end-of-semester course evaluations about experiences and interactions with older
      adults during the course.

PMID- 16564471
TI  - Incorporating geriatrics into baccalaureate nursing curricula: laying the
      groundwork with faculty development.
AB  - In June 2001, the John A. Hartford Foundation of New York awarded the American
      Association of Colleges of Nursing (AACN) a 3.99 million dollar grant to enhance
      gerontology curriculum development and new clinical experiences in 20
      baccalaureate and 10 graduate schools of nursing. Over the 4-year grant
      implementation period, AACN learned a valuable lesson from the grant's site
      directors: Faculty development is the single most necessary precursor to the
      successful implementation and maintenance of geriatric curricular enhancements.
      Unless faculty members foster positive attitudes toward aging, expand their
      geriatric nursing knowledge base, and are able to integrate geriatric content
      into the curricula, progress cannot be made. Enhancing Geriatric Nursing
      Education project directors recommend that the following steps be taken toward
      the creation of successful faculty development activities: (1) anoint a champion
      to mentor and persuade faculty members to embrace gerontology; (2) garner faculty
      buy-in by engaging the faculty early so that they become active participants in
      the curricular change process; (3) assess faculty knowledge and comfort level by
      administering tools developed by the John A. Hartford Foundation Institute for
      Geriatric Nursing and by conducting surveys based on AACN geriatric core
      competencies; (4) conduct faculty development workshops that include cutting-edge
      knowledge and research and provide the faculty with opportunities to discuss
      feelings and stereotypes about aging; (5) elicit the dean's support to encourage
      and allow time and opportunities for training; and (6) use the many excellent
      resources that help the faculty integrate geriatric content into their courses.
      This article will further elucidate such strategies and will highlight the range
      of faculty development activities in which grant-funded schools engaged.

PMID- 16564472
TI  - The journey toward geriatric excellence in a non-research-intensive university.
AB  - In response to the unprecedented rise in the U.S. older adult population, nurse
      educators have intensified efforts to produce graduates who are sensitive to
      older adults' health care concerns. Critical to accomplishing this goal is
      strengthening curricula to include specialized gerontological content. Although
      the science of gerontological nursing has grown significantly over the past
      several decades, large-scale research projects are often confined to research or
      doctoral level universities in which typically more support is available. Faculty
      members in smaller universities in which a great number of nursing students are
      educated do not always have the resources to readily contribute to science. Such
      a challenge was faced by one nursing school in a small Jesuit New England
      university. This article illustrates a process to develop excellence in
      gerontological nursing education, as well as to promote scholarship and
      collaboration among faculty members at baccalaureate or master's level
      universities. Three years ago, the John A. Hartford Foundation, in collaboration
      with the American Association of Colleges of Nursing, awarded grants to select
      nursing programs for curricular enhancement. Implementation of this project at a
      small Jesuit university led to synergy among faculty that resulted in joint
      publications, presentations, and newly funded projects. In addition, the school
      earned local and national recognition for excellence in gerontological nursing
      education/care. The process leading to the outstanding success of this curricular
      endeavor is presented as a replicable model for schools in other baccalaureate or
      master's level settings.

PMID- 16564473
TI  - Improving knowledge and attitudes toward older adults through innovative
      educational strategies.
AB  - Our country's rapidly growing older adult population represents the core business
      of health care; however, few nurses are adequately prepared to care for their
      unique needs. This is caused, in part, by the limited attention paid by nursing
      educators to incorporating basic gerontological nursing principles into
      undergraduate programs. During the last 7 years, the American Association of
      Colleges of Nursing, through the generous support of the John A. Hartford
      Foundation, has led several initiatives to improve gerontological nursing
      education in baccalaureate programs. This article describes innovative
      educational strategies successfully implemented by three nursing programs--New
      York University, Tuskegee University, and University of Rhode Island--to increase
      knowledge and improve attitudes of nursing students in caring for older adults.
      Successful strategies include a long-term care guide, a senior mentor experience,
      student assignments addressing diversity issues, student debates, critical
      reflective journalizing, and an evaluation tool for measuring student attitudes.
      These strategies are readily reproducible and assist faculty to easily integrate
      gerontological nursing content into the curriculum while simultaneously enhancing
      student attitudes and knowledge.

PMID- 16564474
TI  - Innovative strategies for incorporating gerontology into BSN curricula.
AB  - To prepare nurses in providing competent care to older adults, schools of nursing
      at the Otterbein College and the Florida International University, supported by
      American Association of Colleges of Nursing/John A. Hartford Foundation,
      developed innovative strategies for incorporation of gerontological content into
      their BSN curricula. Both nursing programs integrated these innovative
      gerontological learning experiences into sophomore-, junior-, and senior-level
      baccalaureate courses; developed independent gerontology courses, including
      online courses; supported the development of faculty expertise and sensitivity in
      elder care; and established new and/or enhanced existing community partnerships.
      The program objectives, planning, and implementation procedures for each of the
      two schools evolved similarly. Faculty development strategies and examples of
      community and international partnerships are presented. Finally, lessons learned
      from the implementation of these projects and recommendations based on these
      initiatives are presented.

PMID- 16564475
TI  - An educational framework to support gerontological nursing education at the
      baccalaureate level.
AB  - Building gerontological content into a nursing curriculum will help meet the
      rising nursing care needs of older adults. An educational framework used to
      support innovative teaching and learning strategies is presented. Using this
      framework, strategies for developing and teaching a new undergraduate nursing
      elective include exposure to and interactions with older adults, national
      conference attendance, and use of film to investigate issues of aging. A topical
      outline of the course, assignments, and additional teaching strategies are
      presented. To date, 58 students have reported high satisfaction and increased
      interest in gerontological nursing. Twenty-three percent of graduating nurses
      enrolled in this course and received specialty content in the care of older
      adults. Faculty satisfaction remained high. The innovative teaching strategies
      enhanced faculty and student engagement in course content. The successful use of
      these strategies should be considered for implementation in both elective and
      required courses that focus on gerontological nursing.

PMID- 16564476
TI  - Education/community collaborations for undergraduate nursing gerontological
      clinical experiences.
AB  - In 2000, the American Association of Colleges of Nursing and the John A. Hartford
      Foundation Institute for Geriatric Nursing developed guidelines to help nurse
      educators incorporate gerontological nursing content into baccalaureate
      curricula. In 2001, the Hartford Foundation also provided grant monies to nursing
      programs to support gerontology curricular innovations and new clinical
      experiences. The funding allowed faculty to focus time, energy, and resources on
      gerontological nursing education. We, the authors, representing two funded
      schools of nursing, collaborated with community agencies to develop undergraduate
      gerontological clinical learning experiences and are encouraged by the results.
      This article describes the development of these collaborations and serves as a
      model for other schools of nursing. The education/community collaborations
      described here focus on clinical learning strategies, implementation activities,
      and outcomes/benefits of the experiences. Both educational programs had
      supportive administration, faculty willing to participate in curriculum change,
      organized plans to implement geriatric curricular enhancement, and long-standing
      community partnerships.

PMID- 16564477
TI  - Assessment of geriatric knowledge: an online tool for appraising entering APN
      students.
AB  - As the percentage of elderly in the U.S. rises, the need for primary health care
      for the aging population increases. Knowledge of special characteristics of older
      persons, as well as demographics of the aging population, resources and
      principles of care are important in the provision of effective, professional
      primary health care by advanced practice nurses. In response to this increasing
      need for geriatric health care expertise, a tool was developed to evaluate basic
      geriatric knowledge of students entering advanced practice nursing study, Self
      Assessment of Geriatric Knowledge. The Self Assessment, derived from AACN's
      recommended geriatric competencies for BSN graduates, may be accessed on-line.
      Immediate test results are received on-line. Tests completed by 158 advanced
      practice students over a three year period showed geriatric knowledge deficits:
      myths of aging, prevention strategies and risk factors of elders; roles and
      responsibilities for care of elderly persons in the community; health policies
      that affect elder care; and, demographics of the geriatric population. These data
      may contribute to faculty awareness of curricular needs for preparing students
      for competent geriatric nursing care of the growing older population.

PMID- 16564478
TI  - A necessity not a luxury: preparing advanced practice nurses to care for older
      adults.
AB  - Of today's 2.7 million registered nurses, less than 1% are certified in
      gerontological nursing and only 3% of advanced practice nurses (APNs) have
      specialized training in this area. These statistics indicate that there are not
      enough gerontological nurse practitioners or geriatric clinical nurse specialists
      to care for the burgeoning older adult population. Relying solely on certified
      geriatric APNs to care for older adults is not a viable solution. Educating all
      APNs with grounding in gerontological nursing care may well be the answer to
      expanding our nation's capacity to competently care for our rapidly aging
      population. As part of the 4-year Enhancing Geriatric Nursing Education in
      Baccalaureate and Advanced Practice Nursing Grant, the American Association of
      Colleges of Nursing developed a set of core gerontological competencies for
      graduate APN programs. These competencies, entitled Nurse Practitioner and
      Clinical Nurse Specialist Competencies for Older Adult Care, delineate guidelines
      for APNs who are not specialists in gerontology but provide care to older adults.
      This article describes the competency development process, provides an overview
      of broad categories and examples of competency statements, and highlights model
      case studies for integrating gerontological content throughout APN curricula to
      ensure that graduates are equipped to provide competent care to older adults.

PMID- 16564479
TI  - Integrating gerontology competencies into graduate nursing programs.
AB  - Current demographic and health care utilization trends strongly indicate a
      rapidly increasing demand for nurses who are well qualified to care for older
      adults. Advanced practice nurses are positioned to assume leadership roles in
      geriatric nursing care; however, they must first acquire adequate preparatory
      education. This article describes two graduate nursing schools' curricular
      innovations that were funded by The John A. Hartford Foundation, in collaboration
      with the American Association of Colleges of Nursing (AACN), through the
      Geriatric Nursing Education Project: Enhancing Gerontological/Geriatric Nursing
      for Advanced Practice Nursing. These programs at University of North Carolina at
      Greensboro and Pennsylvania State University incorporated techniques to translate
      the Nurse Practitioner and Clinical Nurse Specialist Competencies for Older Adult
      Care [American Association of Colleges of Nursing. (2004). Nurse practitioner and
      clinical nurse specialist competencies for older adult care. Washington, DC:
      AACN] into an advanced practice curriculum and developed strategies to sustain
      curricular innovations. Finally, lessons learned from these two projects are
      discussed and recommendations are made for integrating geriatric nursing
      competencies into graduate programs.

PMID- 16564480
TI  - Enriching geropsychiatric nursing in advanced practice nursing programs.
AB  - The need for advanced practice nurses with knowledge and skills in
      geropsychiatric nursing is real and looming larger than ever. By 2030, the number
      of older adults with major psychiatric illnesses is predicted to reach 15
      million. Preparing advanced practice nurses with mental health and
      geropsychiatric nursing expertise is essential. This paper describes three
      innovative curricular models for addressing geropsychiatric nursing in graduate
      advanced practice nursing programs. These models can be implemented with vision,
      planning, modest resources, and the cooperation of the faculty.

PMID- 16564481
TI  - Lessons learned from a mentored graduate program in gerontological nursing.
AB  - An educational training grant provided the funding for a 3-year project to
      recruit candidates into a mentored and redesigned gerontological advanced
      practice nursing program. The project goal was to design and implement a part
      time program in advanced practice gerontological nursing that allowed nurses
      currently working in a long-term care (LTC) facility to maintain their full-time
      employment. Most of the students recruited worked at a partner LTC facility. The
      cohort was ethnically diverse. The outcome objective is board certification in
      gerontological advanced practice nursing. The mentored model offered a high level
      of support, including tutoring, professional role development activities, writing
      support, regular meetings, and workshops. Project faculty learned valuable
      lessons from this project relating to mentoring, tutoring, course scheduling,
      learning styles and preferences, and writing support. The part-time curriculum
      should also be reviewed critically.

PMID- 16564483
TI  - Effects of associative learning on age differences in task-set switching.
AB  - Costs of switching between tasks may disappear when subjects are able to learn
      associations between tasks, stimuli, and responses (cf. Rogers, R. D., & Monsell,
      S. (1995). Costs of a predictable switch between simple cognitive tasks. Journal
      of Experimental Psychology: General, 124, 207-231). The first aim of this study
      was to examine this possibility by manipulating stimulus-set size. We expected
      that costs of switching between tasks would be strongly reduced under conditions
      of small stimulus-set sizes (n=4) as compared to large stimulus-set sizes (n=96)
      with increasing time on task. The second aim was to determine whether younger as
      well as older adults were able to create associations between task components. As
      age differences in task switching are often found to be larger when response
      mappings are incompatible we also investigated interactions with response
      compatibility. Results of our study indicated that practice effects on switch
      costs were much more pronounced for small than large stimulus-set sizes,
      consistent with the view that the strength of associations between task
      components facilitates task switching. Furthermore, we found that practice
      benefits on task switching for small stimulus-set sizes were sensitive to age and
      response compatibility. In contrast to younger adults, who showed a reduction of
      switch costs for both response mapping conditions, older adults showed a
      reduction of switch costs only when response mappings were compatible. That is,
      older adults showed less associative learning when the currently irrelevant task
      feature had to be suppressed, supporting the view that older adults have
      primarily problems in separating overlapping task-set representations.

PMID- 16564485
TI  - High-performance liquid chromatography coupled with tandem mass spectrometry
      applied for metabolic study of ginsenoside Rb1 on rat.
AB  - Liquid chromatography coupled with mass spectrometry and tandem mass spectrometry
      has been applied to investigate the in vivo metabolism of ginsenoside Rb(1) in
      rat. Both positive electrospray ionization mass spectrometry and negative
      electrospray ionization mass spectrometry were used to identify the Rb(1) and its
      metabolites in rat plasma, urine, and feces samples. Oxygenation and
      deglycosylation were found to be the major metabolic pathways of Rb(1) in rat. A
      total of nine metabolites were detected in urine and feces samples collected
      after intravenous and oral administration. Deglycosylated metabolism of Rb(1)
      generated other ginsenosides as the major metabolites, such as Rd, Rg(3) or F(2),
      Rh(2), or C-K. This result indicates that the ginsenoside Rb(1) has many
      pharmacological activities and could be used as a prodrug.

PMID- 16564484
TI  - Metabolipidomics: profiling metabolism of glycerophospholipid species by stable
      isotopic precursors and tandem mass spectrometry.

PMID- 16564486
TI  - High-level expression of proteins in Escherichia coli using a pETCX10 expression
      system.

PMID- 16564487
TI  - Cell-surface-localized ATP detection with immobilized firefly luciferase.
AB  - We demonstrate the application of an assay technique for the detection of ATP
      efflux from the cell surface. Until recently, the firefly luciferase assay has
      conventionally been used to detect ATP release because of its high sensitivity
      and wide detection ability. However, since this technique can be used only to
      infer the amount of diffused ATP in bulk solutions, it does not accurately
      reflect the dynamic ATP flux at the cell membrane. We therefore constructed
      luciferase fusion proteins that could be immobilized onto the cell surface.
      However, the low activities and limited application ranges of these proteins
      prompted us to use biotinylated luciferase given its attributes of strong and
      stable localization. Furthermore, luciferase can be immobilized strongly onto the
      biotinylated cell surface via streptavidin-biotin binding and can thus be used to
      determine the dynamic release of ATP near the cell surface.

PMID- 16564488
TI  - Absolute quantification of farnesylated Ras levels in complex samples using
      liquid chromatography fractionation combined with tryptic digestion and
      electrospray tandem mass spectrometry.
AB  - Farnesylation is the first posttranslational modification of H-Ras proteins,
      which can be blocked by farnesyl transferase inhibitors. We developed a sensitive
      and quantitative bioanalytical assay to determine the absolute amounts of
      farnesylated H-Ras in tumor cell lysates before and after administration of these
      compounds. Farnesylated H-Ras was isolated with reversed-phase liquid
      chromatography. Subsequently, the isolated fraction was digested with trypsin and
      analyzed with electrospray-tandem mass spectrometry. The farnesylated peptide
      consisting of cysteine-valine-leucine-serine (f-CVLS) proved to be a suitable
      signature peptide. Its deuterated analogue was used as internal standard for
      absolute quantification. With this method, we obtained a lower limit of
      quantification of 8pmol farnesylated H-Ras in cell lysates. We demonstrate that
      this method can be used to determine IC(50) values of farnesyl transferase
      inhibitors through absolute quantification of the amount of f-CVLS present after
      incubation with different concentrations of a farnesyl transferase inhibitor. The
      signature peptide approach combined with prefractionation may be used as a
      pharmacodynamic assay to determine dose-effect relationships of farnesyl
      transferase inhibitors in (pre)clinical studies.

PMID- 16564489
TI  - Antioxidant inhibition of oxygen radicals for measurement of total antioxidant
      capacity in biological samples.
AB  - Few methods for assessing total antioxidant capacity (TAC) include both the
      percentage of inhibition and the length of inhibition in the measurement.
      Available methods require above ambient constant temperature incubation, reaction
      preheating, and/or separate assays for testing hydrophilic and hydrophobic
      samples. We describe a high-throughput method, antioxidant inhibition of oxygen
      radicals (AIOR), that overcomes these difficulties. AIOR uses peroxyl radicals to
      trigger a decrease in fluorescence of the indicator molecule, uroporphyrin I,
      which is delayed by the presence of antioxidants. The area under the curve is
      measured by a fluorescence spectrophotometer in a 96-well microplate format, and
      TAC results are expressed as millimole/liter Trolox equivalents. AIOR is
      performed at ambient temperature and is applicable to samples in either aqueous
      or common organic solvents. The reaction between uroporphyrin I and the peroxyl
      radicals generated from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) was
      found to be of first-order kinetics with a mean rate constant (k) of 0.0254.
      Applications to measure antioxidant capacity are demonstrated on individual
      chemicals and biological samples. The method has good linearity, within- and
      between-assay precision, and recovery.

PMID- 16564490
TI  - A quenched fluorescent dipeptide for assaying dispase- and thermolysin-like
      proteases.
AB  - Metalloproteases such as dispase and thermolysin play a crucial role in the life
      cycle of bacteria. Commonly, they prefer hydrophobic amino acids at P1' of
      substrate proteins, thereby cleaving the peptide bond at the alpha amino group.
      Activity of such proteases has been measured by the use of tailor-made
      oligopeptides provided with fluorescence resonance energy transfer dyes. We can
      now show that the short dipeptide Dabcyl-Ser-Phe-EDANS is an appropriate
      substrate of dispase and thermolysin. It was cleaved by both enzymes at the
      single peptide bond accompanied by a steep increase in fluorescence. Substantial
      quenching effects of the formed products were observed only when more than
      80microM substrate was hydrolyzed. High affinity of the proteases for the
      dipeptide resulted in low K(m) values of 91+/-9 and 104+/-18microM, which are
      comparable to those measured for longer peptides. Dabcyl-Ser-Phe-EDANS was also
      used to determine the pH and optimal temperature of dispase, which were found at
      pH 7.0 and 50 degrees C. Buffer substances such as acetate, citrate, and
      tris(hydroxymethyl)aminomethane had no significant effect on enzyme activity.
      Measurements up to 100 degrees C revealed that hydrolysis of the quenched
      fluorescent dipeptide took place only in the presence of active dispase.

PMID- 16564491
TI  - S-(4,4'-Dimethoxytrityl)-3-mercaptopropionic acid, an efficient reagent for
      estimation of epoxy functionalities on microslides used for biochips.

PMID- 16564492
TI  - [What is the preferred approach to perform appendectomy in a young man?
      Laparoscopic or conventional technique?].

PMID- 16564493
TI  - Swine teeth as potential substitutes for in vitro studies in tooth adhesion: a
      SEM observation.
AB  - Animal teeth are routinely used in studies that test dental materials; however,
      no studies have yet proposed the use of swine teeth in laboratory tests. The
      purpose of this study was to compare the effects of acid etching on the dentine
      and enamel of human and swine teeth, aiming at the use of swine teeth as
      substitutes for human teeth in adhesion tests. Four human molars and four swine
      molars free of caries were used. For the study of enamel, two human and two swine
      teeth were longitudinally sectioned with a dental handpiece and a carborundum
      disk. For evaluation of dentine, the remaining teeth had the occlusal third of
      their crowns removed using a low speed diamond saw. All specimens underwent acid
      etching with 37% phosphoric acid for 30s. The etched surfaces were then washed
      with air/water spray for 10s. The specimens were then prepared for analysis in a
      Sterioscan 440 scanning electron microscope. It was observed a similar morphology
      in human and swine teeth, despite swine enamel was thinner than human enamel.
      Acid etching of swine enamel promoted a demineralization similar to that observed
      in human enamel in which the three types of Silverstone's patterns were observed.
      Acid etching of dentine exposed the opening of dentinal tubules in both swine and
      human teeth. Peritubular dentine was removed by phosphoric acid, while collagen
      fibrils appeared discernible in intertubular dentine. Thus, this study showed
      that enamel and dentine from swine and human teeth share many structural
      similarities after acid etching.

PMID- 16564494
TI  - Role of membrane lipids in the mechanism of bacterial species selective toxicity
      by two alpha/beta-antimicrobial peptides.
AB  - We have previously shown that two synthetic antimicrobial peptides with
      alternating alpha- and beta-amino acid residues, designated simply as alpha/beta
      peptide I and alpha/beta-peptide II, had toxicity toward bacteria and affected
      the morphology of bacterial membranes in a manner that correlated with their
      effects on liposomes with lipid composition similar to those of the bacteria. In
      the present study we account for the weak effects of alpha/beta-peptide I on
      liposomes or bacteria whose membranes are enriched in phosphatidylethanolamine
      (PE) and why such membranes are particularly susceptible to damage by alpha/beta
      peptide II. The alpha/beta-peptide II has marked effects on unilamellar vesicles
      enriched in PE causing vesicle aggregation and loss of their internal aqueous
      contents. The molecular basis of these effects is the ability of alpha/beta
      peptide II to induce phase segregation of anionic and zwitterionic lipids as
      shown by fluorescence and differential scanning calorimetry. This phase
      separation could result in the formation of defects through which polar materials
      could pass across the membrane as well as form a PE-rich membrane domain that
      would not be a stable bilayer. alpha/beta-Peptide II is more effective in this
      regard because, unlike alpha/beta-peptide I, it has a string of two or three
      adjacent cationic residues that can interact with anionic lipids. Although
      alpha/beta-peptide I can destroy membrane barriers by converting lamellar to non
      lamellar structures, it does so only weakly with unilamellar vesicles or with
      bacteria because it is not as efficient in the aggregation of these membranes
      leading to the bilayer-bilayer contacts required for this phase conversion. This
      study provides further understanding of why alpha/beta-peptide II is more toxic
      to micro-organisms with a high PE content in their membrane as well as for the
      lack of toxicity of alpha/beta-peptide I with these cells, emphasizing the
      potential importance of the lipid composition of the cell surface in determining
      selective toxicity of anti-microbial agents.

PMID- 16564496
TI  - Three distinct roles of aquaporin-4 in brain function revealed by knockout mice.
AB  - Aquaporin-4 (AQP4) is expressed in astrocytes throughout the central nervous
      system, particularly at the blood-brain and brain-cerebrospinal fluid barriers.
      Phenotype analysis of transgenic mice lacking AQP4 has provided compelling
      evidence for involvement of AQP4 in cerebral water balance, astrocyte migration,
      and neural signal transduction. AQP4-null mice have reduced brain swelling and
      improved neurological outcome in models of (cellular) cytotoxic cerebral edema
      including water intoxication, focal cerebral ischemia, and bacterial meningitis.
      However, brain swelling and clinical outcome are worse in AQP4-null mice in
      models of vasogenic (fluid leak) edema including cortical freeze-injury, brain
      tumor, brain abscess and hydrocephalus, probably due to impaired AQP4-dependent
      brain water clearance. AQP4 deficiency or knock-down slows astrocyte migration in
      response to a chemotactic stimulus in vitro, and AQP4 deletion impairs glial scar
      progression following injury in vivo. AQP4-null mice also manifest reduced sound-
      and light-evoked potentials, and increased threshold and prolonged duration of
      induced seizures. Impaired K+ reuptake by astrocytes in AQP4 deficiency may
      account for the neural signal transduction phenotype. Based on these findings, we
      propose modulation of AQP4 expression or function as a novel therapeutic strategy
      for a variety of cerebral disorders including stroke, tumor, infection,
      hydrocephalus, epilepsy, and traumatic brain injury.

PMID- 16564495
TI  - Permeation and inhibition of polycystin-L channel by monovalent organic cations.
AB  - Polycystin-L (PCL), homologous to polycystin-2 (71% similarity in protein
      sequence), is the third member of the polycystin family of proteins. Polycystin-1
      and -2 are mutated in autosomal dominant polycystic kidney disease, but the
      physiological role of PCL has not been determined. PCL acts as a Ca-regulated non
      selective cation channel permeable to mono- and divalent cations. To further
      understand the biophysical and pharmacological properties of PCL, we examined a
      series of organic cations for permeation and inhibition, using single-channel
      patch clamp and whole-cell two-microelectrode voltage clamp techniques in
      conjunction with Xenopus oocyte expression. We found that PCL is permeable to
      organic amines, methlyamine (MA, 3.8 A), dimethylamine (DMA, 4.6 A) and
      triethylamine (TriEA, 6 A), and to tetra-alkylammonium cation (TAA) tetra
      methylammonium (TMA, 5.5-6.4 A). TAA compounds tetra-ethylammonium (TEA, 6.1-8.2
      A) and tetra-propylammonium (TPA, 9.8 A) were impermeable through PCL and
      exhibited weak inhibition on PCL (IC50 values>13 mM). Larger TAA cations tetra
      butylammonium (TBA, 11.6 A) and tetra-pentylammonium (TPeA, 13.2 A) were
      impermeable through PCL as well and showed strong inhibition (IC50 values of 2.7
      mM and 1.3 microM, respectively). Inhibition by TBA was on decreasing the single
      channel current amplitude and exhibited no effect on open probability (NPo) or
      mean open time (MOT), suggesting that it blocks the PCL permeation pathway. In
      contract, TEA, TPA and TPeA reduced NPo and MOT values but had no effect on the
      amplitude, suggesting their binding to a different site in PCL, which affects the
      channel gating. Taken together, our studies revealed that PCL is permeable to
      organic amines and TAA cation TMA, and that inhibition of PCL by large TAA
      cations exhibits two different mechanisms, presumably through binding either to
      the pore pathway to reduce permeant flux or to another site to regulate the
      channel gating. These data allow to estimate a channel pore size of approximately
      7 A for PCL.

PMID- 16564497
TI  - Mitochondrial regulation of hypoxia-induced increase of adrenomedullin mRNA in HL
      1 cells.
AB  - Hypoxia upregulates the expression of the cardioprotective peptide adrenomedullin
      in cardiomyocytes. We characterized this pathway in murine HL-1 cardiomyocytes.
      Inhibition of mitochondrial complexes I, III, and IV largely, but not completely,
      reduced hypoxic adrenomedullin mRNA increase in gas-impermeable culture plates.
      Complex III inhibition was also effective in permeable culture plates, so that
      this effect is unlikely due to intracellular oxygen redistribution, whereas
      complex I blockade was ineffective in permeable plates. Complex II does not
      participate in this effect, as shown by chemical and siRNA inactivation. ROS
      scavenging by nitroblue tetrazolium and general flavoprotein inhibition by
      diphenyleniodonium nearly abrogated the hypoxic adrenomedullin mRNA increase.
      Thus, ROS production by flavoproteins is crucial for hypoxic upregulation of
      adrenomedullin mRNA in murine HL-1 cardiomyocytes. These ROS originate both from
      the mitochondrial complex III and from additional, presumably extramitochondrial,
      sources. Mitochondrial oxygen consumption appears to have impact on oxygen
      availability at these extramitochondrial sensors.

PMID- 16564498
TI  - The pH-dependence of photochemical intermediates of O and P in bacteriorhodopsin
      by continuous light.
AB  - The pH-dependence of the O and P intermediates in the photocycle of
      bacteriorhodopsin (bR) on the intensity and duration of the exciting flash was
      investigated for bR glycerol suspensions and bR gelatin films. Green and red
      laser flashes (532 and 670 nm) were utilized to generate a photoequilibrium state
      of bR and O at ambient temperature, and UV-vis spectroscopy was used to determine
      the photoconversion for the bR suspensions and films. The maximal concentration
      of the O intermediate was observed to be pH-dependent and the dependency was most
      pronounced at a slightly alkaline pH values. The photochemical conversion from
      the O to P intermediate was investigated for both bR suspensions and films. The P
      intermediate was only found in bR gelatin film. These results indicate that bR
      gelatin film may be an attractive candidate for the information storage based on
      P intermediate. It is possible, with red light, to create photoproducts which are
      thermally stable at ambient temperature and that can be photochemically erased.

PMID- 16564500
TI  - Evaluation of the anti-hepatitis C virus effects of cyclophilin inhibitors,
      cyclosporin A, and NIM811.
AB  - Hepatitis C virus (HCV) is a major causative agent of hepatocellular carcinoma.
      We recently discovered that the immunosuppressant cyclosporin A (CsA) and its
      analogue lacking immunosuppressive function, NIM811, strongly suppress the
      replication of HCV in cell culture. Inhibition of a cellular replication
      cofactor, cyclophilin (CyP) B, is critical for its anti-HCV effects. Here, we
      explored the potential use of CyP inhibitors for HCV treatment by analyzing the
      HCV replicon system. Treatment with CsA and NIM811 for 7 days reduced HCV RNA
      levels by 2-3 logs, and treatment for 3 weeks reduced HCV RNA to undetectable
      levels. NIM811 exerted higher anti-HCV activity than CsA at lower concentrations.
      Both CyP inhibitors rapidly reduced HCV RNA levels even further in combination
      with IFNalpha without modifying the IFNalpha signal transduction pathway. In
      conclusion, CyP inhibitors may provide a novel strategy for anti-HCV treatment.

PMID- 16564501
TI  - Differential effect of calcium ions on the cytosolic and mitochondrial
      thioredoxin reductase.
AB  - The effect of calcium ions has been studied on three different isoforms of
      thioredoxin reductase. The cytosolic (TrxR1), mitochondrial (TrxR2), and the
      Escherichia coli enzymes were examined and compared. In our condition, TrxR1
      appears extremely sensitive to Ca2+ showing an IC50 of about 160 nM, while Ca2+
      exerts only a weak inhibitory effect on the mitochondrial isoform. The
      thioredoxin reductase purified from E. coli is almost completely insensitive to
      calcium ions. Circular dichroism analysis of highly purified mitochondrial and
      cytosolic thioredoxin reductases reveals that Ca2+ induces conformational
      alterations that are particularly relevant only in the cytosolic isoform. These
      observations are discussed with reference to the physiological role and, in
      particular, to the regulatory functions of the thioredoxin system.

PMID- 16564502
TI  - Ricin A chain reaches the endoplasmic reticulum after endocytosis.
AB  - Ricin is a potent ribosome inactivating protein and now has been widely used for
      synthesis of immunotoxins. To target ribosome in the mammalian cytosol, ricin
      must firstly retrograde transport from the endomembrane system to reach the
      endoplasmic reticulum (ER) where the ricin A chain (RTA) is recognized by ER
      components that facilitate its membrane translocation to the cytosol. In the
      study, the fusion gene of enhanced green fluorescent protein (EGFP)-RTA was
      expressed with the pET-28a (+) system in Escherichia coli under the control of a
      T7 promoter. The fusion protein showed a green fluorescence. The recombinant
      protein can be purified by metal chelated affinity chromatography on a column of
      NTA. The rabbit anti-GFP antibody can recognize the fusion protein of EGFP-RTA
      just like the EGFP protein. The cytotoxicity of EGFP-RTA and RTA was evaluated by
      the MTT assay in HeLa and HEP-G2 cells following fluid-phase endocytosis. The
      fusion protein had a similar cytotoxicity of RTA. After endocytosis, the
      subcellular location of the fusion protein can be observed with the laser
      scanning confocal microscopy and the immuno-gold labeling Electro Microscopy.
      This study provided important evidence by a visualized way to prove that RTA does
      reach the endoplasmic reticulum.

PMID- 16564503
TI  - Direct binding of recombinant plasminogen kringle 1-3 to angiogenin inhibits
      angiogenin-induced angiogenesis in the chick embryo CAM.
AB  - Angiogenin is one of the most potent angiogenesis-inducing proteins. Angiostatin
      is one of the most potent angiogenesis inhibitors, and it contains the first four
      kringle domains of plasminogen (K1-4). Recombinant human plasminogen kringle 1-3
      (rK1-3) was expressed in Escherichia coli and purified to homogeneity. The
      binding of t-4-aminomethylcyclohexanecarboxylic acid with the purified kringle 1
      3 was determined by changes in intrinsic fluorescence. rK1-3 exhibits comparable
      ligand-binding properties as native human plasminogen kringle 1-3. The purified
      rK1-3 inhibits neovascularization in the chick embryo chorioallantoic membrane
      (CAM) assay. Interaction of angiogenin with rK1-3 was examined by immunological
      binding assay and surface plasmon resonance kinetic analysis, and the equilibrium
      dissociation constants for the complex, Kd, are 0.89 and 0.18 microM,
      respectively. rK1-3 inhibits angiogenin-induced angiogenesis in the chick embryo
      CAM in a concentration-dependent manner. These results indicate that rK1-3
      directly binds to angiogenin and thus rK1-3 inhibits the angiogenic activity of
      angiogenin.

PMID- 16564505
TI  - The selective m1 muscarinic antagonist MT-7 blocks pilocarpine-induced striatal
      Fos expression.
AB  - Systemic administration of the nonselective muscarinic agonist pilocarpine
      induces pronounced striatal Fos expression. Intrastriatal injections of the mamba
      snake toxin MT-7, a highly selective and irreversible m1 muscarinic antagonist,
      drastically attenuated this response when given 2, but not 8, days before
      pilocarpine. In contrast, MT-7 did not alter the response to amphetamine (5
      mg/kg). These results suggest that pilocarpine induces Fos expression in the
      striatum as a result of stimulating m1 muscarinic receptors located within this
      structure and demonstrate the utility of the MT-7 for in vivo studies of
      cholinergic function.

PMID- 16564504
TI  - Down-regulation of the expression of beta1,4-galactosyltransferase V promotes
      integrin beta1 maturation.
AB  - In previous study, we have shown that beta1,4-galactosyltransferase V (GalT V)
      functions as a positive growth regulator in glioma. Here, we reported that down
      regulation of the expression of GalT V in SHG44 cells by transfection with
      antisense cDNA specifically up-regulated the expression of cell surface integrin
      beta1 without the change of its mRNA, and with integrin beta1 125 kDa mature form
      increased and 105 kDa precursor form decreased. It is well known that the N
      glycans of integrins modulate the location and functions of integrins. The SHG44
      cells transfected with antisense cDNA of GalT V demonstrated decreased Golgi
      localization of integrin beta1, strengthened the interaction between integrin
      alpha5 and beta1 subunit, and enhanced the adhesion ability to fibronectin and
      the level of focal adhesion kinase phosphorylation. Our results suggested that
      the down-regulation of the expression of GalT V could promote the expression of
      cell surface integrin beta1 and subsequently inhibit glioma malignant phenotype.

PMID- 16564506
TI  - Progressive hearing loss in mice carrying a mutation in the p75 gene.
AB  - The neurotrophin receptor p75 (p75NTR) is expressed in the developmental stage of
      the cochlea. However, the role of the p75NTR in the inner ear remains to be
      established. In this study, we conducted electrophysiological and morphological
      analyses of the auditory function of mice carrying a mutation in the p75 gene at
      different longitudinal stages. The mice carrying a mutation in the p75 gene
      showed an age-related progressive hearing loss. At 1 month, there was no obvious
      morphological change in the cochlea of the mice carrying a mutation in the p75
      gene compared to wild-type mice, except for a slight loss of spiral ganglion
      neurons (SGNs). Auditory function was not significantly different between both
      genotypes from 1 to up to 4 months of age. The mice carrying a mutation in the
      p75 gene started to show progressive hearing loss at 4 months, when both SGN
      degeneration and hair cell (HC) loss were observed at the basal turn. These
      results suggest that the neurotrophin receptor p75 may play a significant role in
      the maintenance of cochlear function, and that mice carrying a mutation in the
      p75 gene could be a good animal model of early onset progressive hearing loss.

PMID- 16564507
TI  - Strategies for managing an ever increasing mutant mouse repository.
AB  - Over 10,000 mouse strains and more than 20,000 mouse ES cells containing gene
      trapped or targeted mutations are available to researchers. The mouse strains and
      stocks include those with spontaneous, genetically engineered and induced
      mutations, as well as 100s of inbred strains and strain panels, valuable for
      quantitative trait locus (QTL) and modifier gene identification. Current
      worldwide initiatives are expected to result in multiple mutations in every mouse
      gene in the first 10 years of the 21st century. Managing the rapid and cost
      effective distribution of these burgeoning resources to scientists around the
      world will be challenging for scientists and mouse repositories. Here we describe
      new strategies for managing and distributing mice.

PMID- 16564499
TI  - Gene expression profiling between embryonic and larval stages of the silkworm,
      Bombyx mori.
AB  - To elucidate the molecular mechanisms associated with metamorphic phenomenon
      relating to Bombyx mori, an important organism in the sericulture industry, we
      identified genes that are expressed in the different developmental stages,
      specifically the embryonic (ES) and larval (LS) stages of B. mori. Of 8230 high
      quality ESTs from two full-length enriched cDNA libraries, 3442 of the ES ESTs
      were coalesced into 1325 clusters, while 4788 were coalesced into 927 clusters.
      The functional classification of these ESTs based on Gene Ontology showed that
      the types of genes that are associated with oxidoreductase activity, enzyme
      inhibition, and larval development were highly observed in LS, whereas the types
      of genes that are involved in nucleotide binding, enzyme activity, and protein
      transport activity were highly observed in ES. In addition, when the gene
      expression profile between ES and LS was examined by counting the EST frequencies
      in each library, 69 genes were identified as being either up- or down-regulated
      in the larval stage compared to the embryonic stage (P>0.99) and this was
      confirmed by semi-quantitative RT-PCR. The results show that genes involved in
      proteolysis and peptidolysis, and lipid and carbohydrate metabolism were
      dramatically up-regulated in LS, while those related to protein metabolism,
      DNA/RNA, and coenzymes were highly down-expressed. In particular, a GO analysis
      of these genes revealed that genes that are involved in hydrolase activity were
      observed to be highly expressed in amount as well as diversity in LS, while those
      involved in nucleic acid binding were highly expressed in ES. These data may
      contribute to elucidating genetic events that distinguish the developmental stage
      and to our understanding of the metamorphosis of B. mori.

PMID- 16564508
TI  - Evidence for the presence of the spinal pattern generator involved in the control
      of the genital ejaculatory pattern in the female rat.
AB  - Substantial progress has been made during recent years in elucidating the control
      of male ejaculatory function by the central nervous system. These efforts have
      revealed the participation of a central pattern generator in the control of
      ejaculation. There is a strong similarity in the neural organization of male and
      female sexual functions. In the present study, the hypothesis that the spinal
      generator for ejaculation was present and functional in the female rat was
      evaluated. To this purpose, the expression of the ejaculatory motor pattern and
      its pharmacological activation in spinally transected female rats were
      investigated. Results revealed the presence in females of the already described
      rhythmic ejaculatory motor pattern of male rats. This ejaculatory motor pattern
      could be registered in the urethralis muscle of the female rat after mechanical
      stimulation of the urethra, vagina and clitoris and consisted, as in the male
      rat, of a first ejaculatory motor train followed by an after-discharge component.
      Besides, the female genital ejaculatory motor pattern could be pharmacologically
      induced by the systemic injection of sodium nitroprusside with similar motor
      characteristics. No significant differences between the sensorial and
      pharmacologically induced female genital motor patterns were found. Present
      findings provide evidence for the presence of the genital motor pattern of
      ejaculation in female rats and suggest that the spinal generator for ejaculation
      is also present and functional in this gender.

PMID- 16564509
TI  - The effect of sensory feedback on the timing of movements: evidence from
      deafferented patients.
AB  - The role of sensory feedback in the control of movements was investigated in two
      deafferented patients with complete loss of cutaneous touch and movement/position
      sense below the neck and two control groups of different ages. In a synchronized
      repetitive finger-tapping task in time with a regular auditory pacing signal, the
      deafferented participants showed a strong influence of extrinsic feedback. In
      contrast to controls who demonstrated a typical asynchrony between their taps and
      the pacing signal in all feedback conditions, the deafferented participants, with
      auditory feedback and visual monitoring, showed no asynchrony between finger taps
      and the pacing signal. These findings support the view that sensory information
      plays a crucial role in the anticipatory timing of movements.

PMID- 16564510
TI  - Nicotine reverses consolidated long-term potentiation in the hippocampal CA1
      region.
AB  - Long-term potentiation (LTP) has a memory-like consolidation period during which
      it becomes progressively stabilized. However, it is unknown how the consolidation
      is achieved. The present study demonstrates that nicotine reverses stabilized LTP
      in the hippocampal CA1 region, providing the first evidence that consolidated LTP
      can be reversed. The nicotine-induced reversal appeared to work by reversing
      cellular processes involved in stabilizing LTP, as LTP was readily induced again
      after reversal. The effect of nicotine was mediated, in large part, via
      desensitization of alpha7 nicotinic acetylcholine receptors (nAChRs), as an
      alpha7 nAChR-selective antagonist mimicked the nicotine effect. A non-selective N
      methyl-d-aspartate receptor (NMDAR) antagonist completely abolished the nicotine
      induced reversal, whereas an NR2B-containing NMDAR-selective antagonist had no
      effect. Furthermore, both the protein phosphatase 1/protein phosphatase 2A
      inhibitor okadaic acid and the protein phosphatase 2B (calcineurin) inhibitor
      cyclosporin A blocked the nicotine-induced reversal. Taken together, our results
      suggest that the reversal of stabilized LTP depends on the activation of NR2A
      containing NMDARs and dephosphorylation. Thus, the consolidation of LTP appears
      to be the interruption of signaling leading to NR2A-containing NMDAR-dependent
      activation of protein phosphatases, which can be circumvented by nicotine-induced
      signaling. LTP induced in chronic nicotine-treated hippocampi contained a
      component that is immune to reversal, and thus acute nicotine was no longer
      effective to reverse consolidated LTP. These results demonstrate the differential
      effects of acute and chronic nicotine exposure on the cellular processes that are
      potentially involved in learning and memory.

PMID- 16564511
TI  - Synthesis of N-(beta-D-glucopyranosyl) monoamides of dicarboxylic acids as
      potential inhibitors of glycogen phosphorylase.
AB  - O-peracetylated N-(beta-D-glucopyranosyl)imino trimethylphosphorane obtained in
      situ from 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl azide and PMe3 was reacted
      with saturated and unsaturated aliphatic and aromatic dicarboxylic acids, or
      their anhydrides, or monoesters to give the corresponding N-(beta-D
      glucopyranosyl) monoamides of dicarboxylic acids or derivatives. The acetyl
      protecting groups were removed according to the Zemplen protocol to give a series
      of compounds which showed moderate inhibitory effects against rabbit muscle
      glycogen phosphorylase b. The best inhibitor was 3-(N-beta-D-glucopyranosyl
      carbamoyl)propanoic acid (7) with Ki = 20 microM.

PMID- 16564512
TI  - An efficient synthesis of 2,3-dideoxy-alpha,beta-unsaturated carbohydrate enals
      by mixed Lewis acid (HfCl4 and ZnI2) catalyzed hydration of glycals.
AB  - A new, efficient method has been developed for converting acyl-, arylalkyl- and
      alkyl-protected glycals into corresponding 2,3-dideoxy-alpha,beta-unsaturated
      carbohydrate enals utilizing the in situ generated push-pull effect resulting
      from the synergistic combination of HfCl4 and ZnI2 in catalytic amounts. This new
      procedure eliminates the use of highly toxic Hg2+ ions and acidic conditions
      (0.01-0.02 N H2SO4), besides radically shortening the reaction time.

PMID- 16564513
TI  - Functional effects of a KCNQ1 mutation associated with the long QT syndrome.
AB  - OBJECTIVE: Long QT syndrome (LQTS) is an inherited disorder of ventricular
      repolarization caused by mutations in cardiac ion channel genes, including KCNQ1.
      In this study the electrophysiological properties of a LQTS-associated mutation
      in KCNQ1 (Q357R) were characterized. This mutation is located near the C-terminus
      of S6, a region that is important for the gate structure. METHODS AND RESULTS: Co
      assembly of KCNE1 with the mutant Q357R elicited a current displaying slower
      activation compared to the wild-type KCNQ1/KCNE1 channels. The voltage dependence
      of activation of Q357R was shifted to more positive potentials. Moreover, a
      strong reduction in current density was observed that was partially attributed to
      the altered voltage dependence and kinetics of activation. The reduced current
      amplitude was also caused by intracellular retention of Q357R/KCNE1 channels as
      was shown by confocal microscopy. It indicated that the Q357R mutation disturbed
      protein expression by a trafficking or assembly problem of the Q357R/KCNE1
      complex. To mimic the patient status KCNQ1, Q357R and KCNE1 were co-expressed,
      which revealed a dominant negative effect on current density and activation
      kinetics. CONCLUSION: The effects of the Q357R mutation on the activation of the
      channel together with a reduced expression at the membrane would lead to a
      reduction in I(Ks) and thus in "repolarization reserve" under physiological
      circumstances. As such it explains the long QT syndrome observed in these
      patients.

PMID- 16564514
TI  - Incorporated sarcolemmal fish oil fatty acids shorten pig ventricular action
      potentials.
AB  - BACKGROUND: Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil
      reduce the risk of sudden death presumably by preventing life-threatening
      arrhythmias. Acutely administered omega3-PUFAs modulate the activity of several
      cardiac ion channels, but the chronic effects of a diet enriched with fish oil
      leading to omega3-PUFA-incorporation into the sarcolemma on membrane currents are
      unknown. METHODS: Pigs received a diet either rich in omega3-PUFAs or in omega9
      fatty acids for 8 weeks. Ventricular myocytes (VMs) were isolated and used for
      patch-clamp studies. RESULTS: omega3-VMs contained higher amounts of omega3-PUFAs
      and had a shorter action potential (AP) with a more negative plateau than control
      VM. In omega3 VMs, L-type Ca(2+) current (I(Ca,L)) and Na(+)-Ca(2+) exchange
      current (I(NCX)) were reduced by approximately 20% and 60%, respectively, and
      inward rectifier K(+) current (I(K1)) and slow delayed rectifier K(+) current
      (I(Ks)) were increased by approximately 50% and 70%, respectively, compared to
      control. Densities of rapid delayed rectifier K(+) current, Ca(2+)-activated Cl(
      ) current, and Na(+) current (I(Na)) were unchanged, although voltage-dependence
      of I(Na) inactivation was more negative in omega3 VMs. CONCLUSIONS: A fish oil
      diet increases omega3-PUFA content in the ventricular sarcolemma, decreases
      I(Ca,L) and I(NCX), and increases I(K1) and I(Ks), resulting in AP shortening.
      Incorporation of omega3-PUFAs in the sarcolemma may have consequences for
      arrhythmias independent of circulating omega3-PUFAs.

PMID- 16564515
TI  - Effect of methanol-induced oxidative stress on the neuroimmune system of
      experimental rats.
AB  - It is well known that the nervous system has increased susceptibility to methanol
      intoxication. The present study reveals the effect of methanol intoxication on
      antioxidant status, lipid peroxidation and DNA integrity in hypothalamic
      pituitary-adrenal (HPA) axis organs and spleen. Non-specific and specific immune
      functions were analyzed. In addition, open field behavior, plasma corticosterone
      level and blood methanol level were estimated. Male Wistar albino rats were
      intoxicated with methanol (2.37 g/kg b.wt., i.p.) for 1 day, 15 and 30 days.
      Administration of methanol showed significant increase in enzymatic (superoxide
      dismutase, catalase, glutathione peroxidase), non-enzymatic (reduced glutathione
      and Vitamin C) antioxidants and lipid peroxidation (LPO) in hypothalamus and
      adrenal gland of day 1 group. However, decrease in enzymatic and non-enzymatic
      antioxidants with concomitant increase in LPO level were observed in 15 and 30
      days groups. Plasma corticosterone level was significantly increased in day 1 and
      15 days groups whereas, 30 days methanol intoxication group showed considerable
      decrease in corticosterone level compared with control animals. Cell-mediated
      immune response of footpad thickness was significantly decreased with an
      increased leukocyte migration inhibition. Humoral immune response of antibody
      titers was elevated in methanol-intoxicated groups. Neutrophil functions,
      adherence and phagocytic index (PI) were found to be significantly decreases.
      Furthermore, significant increase in the avidity index and nitro blue tetrozolium
      reduction was observed in the methanol exposed animals. Day 1 methanol exposed
      group showed increased PI compared to the control ones. Methanol exposure for 30
      days showed an increased DNA fragmentation in the hypothalamus, adrenal glands,
      and spleen. In conclusion, exposure to methanol-induced oxidative stress disturbs
      the HPA-axis function altering the level of corticosterone, which lead to varied
      non-specific and specific immune response in experimental rats.

PMID- 16564516
TI  - Time-resolved electron spin resonance studies of spin-labelled lipids in
      membranes.
AB  - Recently, developments in time-resolved spin-label electron spin resonance (ESR)
      spectroscopy have contributed considerably to the study of biomembranes. Two
      different applications of electron spin echo spectroscopy of spin-labelled
      phospholipids are reviewed here: (1) the use of partially relaxed echo-detected
      ESR spectra to study the librational lipid-chain motions in the low-temperature
      phases of phospholipid bilayers; (2) the use of electron spin echo envelope
      modulation spectroscopy to determine the penetration of water into phospholipid
      membranes. Results are described for phosphatidylcholine bilayer membranes, with
      and without equimolar cholesterol, that are obtained with phosphatidylcholine
      spin probes site-specifically labelled throughout the sn-2 chain.

PMID- 16564517
TI  - Pollen-specific pectin methylesterase involved in pollen tube growth.
AB  - Pollen tube elongation in the pistil is a crucial step in the sexual reproduction
      of plants. Because the wall of the pollen tube tip is composed of a single layer
      of pectin and, unlike most other plant cell walls, does not contain cellulose or
      callose, pectin methylesterases (PMEs) likely play a central role in the pollen
      tube growth and determination of pollen tube morphology. Thus, the functional
      studies of pollen-specific PMEs, which are still in their infancy, are important
      for understanding the pollen development. We identified a new Arabidopsis pollen
      specific PME, AtPPME1, characterized its native expression pattern, and used
      reverse genetics to demonstrate its involvement in determination of the shape of
      the pollen tube and the rate of its elongation.

PMID- 16564518
TI  - Optic cup and lens development requires Pax6 expression in the early optic
      vesicle during a narrow time window.
AB  - Pax6 mutations cause complex ocular malformations, but it is uncertain whether
      early eye development normally requires Pax6 function in both the optic vesicle
      (OV) and the lens epithelium, or only in the latter. To investigate this
      question, we electroporated the OV with anti-Pax6 or control morpholinos before
      the onset of lens placode formation. Pax6 downregulation was already detectable
      in the OV 10 h after anti-Pax6 treatment, and was accompanied by a significant
      increase in the death of OV cells. A small eye-like phenotype developed
      thereafter, whose severity was developmental stage-dependent. When treatment was
      applied at Hamburger Hamilton (HH) stage 10, there was no optic cup formation,
      and lens development was abortive despite normal Pax6 expression in the lens
      epithelium. Treatment at HH stage 11 resulted in structurally normal lens and
      optic cup, although the latter showed abnormal expression domains for several
      transcription factors. Early eye development therefore requires cell-autonomous
      Pax6 function not only in the lens but also in the optic vesicle, where it plays
      a hitherto unknown role in cell survival. The results, moreover, indicate that
      there is a critical stage during which Pax6 expression in the OV is necessary for
      normal lens development.

PMID- 16564519
TI  - Identification of an unexpected link between the Shh pathway and a G2/M
      regulator, the phosphatase CDC25B.
AB  - Sonic hedgehog (Shh) signaling controls numerous aspects of vertebrate
      development, including proliferation of precursors in different organs.
      Identification of molecules that link the Shh pathway to cell cycle machinery is
      therefore of major importance for an understanding of the mechanisms underlying
      Shh-dependent proliferation. Here, we show that an actor in the control of entry
      into mitosis, the phosphatase CDC25B, is transcriptionally upregulated by the
      Shh/Gli pathway. Unlike other G2/M regulators, CDC25B is highly expressed in
      domains of Shh activity, including the ventral neural tube and the posterior limb
      bud. Loss- and gain-of-function experiments reveal that Shh contributes to CDC25B
      transcriptional activation in the neural tube both of chick and mouse embryos.
      Moreover, CDC25B transcripts are absent from the posterior limb bud of Shh-/-
      mice, while anterior grafts of Shh-expressing cells in the chicken limb bud
      induce ectopic CDC25B expression. Arresting the cell cycle does not reduce the
      level of CDC25B expression in the neural tube strongly suggesting that the
      upregulation of CDC25B is not an indirect consequence of the Shh-dependent
      proliferation. These data reveal an unexpected developmental link between the Shh
      pathway and a participant in G2/M control.

PMID- 16564520
TI  - Sohlh1 is essential for spermatogonial differentiation.
AB  - Spermatogonia are adult germline stem cells that can both self-renew and
      differentiate into spermatocytes. Little is known about factors necessary for
      spermatogonial differentiation. We identified a novel germ-cell-specific
      transcription factor that we named Sohlh1 (testis and ovary expressed basic helix
      loop-helix (bHLH) transcription factor). In males, Sohlh1 is preferentially
      expressed in prespermatogonia and Type A spermatogonia. Loss of Sohlh1 causes
      infertility by disrupting spermatogonial differentiation into spermatocytes.
      Seven-day-old testes without Sohlh1 still express the testis-specific
      transcription factors Etv5, Taf4b, Zfp148, and Plzf, overexpress a novel Tohlh2
      bHLH transcription factor, but lack LIM homeobox gene Lhx8 and show reduced
      expression of Ngn3. Sohlh1 represents the first testis-specific bHLH
      transcription factor that is essential for spermatogonial differentiation.

PMID- 16564521
TI  - Cerebellar thiol status and motor deficit after lactational exposure to
      methylmercury.
AB  - This study examined the exclusive contribution of methylmercury (MeHg) exposure
      through maternal milk on biochemical parameters related to the thiol status
      (glutathione (GSH) levels, glutathione peroxidase (GPx) and glutathione reductase
      (GR) activities) in the cerebellums of suckling mice. The same biochemical
      parameters were also evaluated in the cerebellums of mothers, which were
      submitted to a direct oral exposure to MeHg (10 mg/L in drinking water). With
      regard to the relationship between cerebellar function and motor activity, the
      presence of signs of motor impairment was also evaluated in the offspring exposed
      to MeHg during lactation. After the treatment (at weaning period), the pups
      lactationally exposed to MeHg showed increased levels of mercury in the
      cerebellum compared to pups in the control group and a significant impairment in
      the motor performance in the rotarod apparatus. In addition, these pups showed
      decreased levels of GSH in the cerebellum compared to pups in the control group.
      In dams, MeHg significantly increased the levels of cerebellar GSH and the
      activities of cerebellar GR. However, this was not observed in pups. This study
      indicates that (1) the exposure of lactating mice to MeHg causes significant
      impairments in motor performance in the offspring which may be related to a
      decrease in the cerebellar thiol status and (2) the increased GSH levels and GR
      activity, observed only in the cerebellums of MeHg-exposed dams, could represent
      compensatory pathophysiologic responses to the oxidative effects of MeHg toward
      endogenous GSH.

PMID- 16564522
TI  - Reversal of MDR1 gene-dependent multidrug resistance using low concentration of
      endonuclease-prepared small interference RNA.
AB  - Multidrug resistance following initial chemotherapy is commonly associated with
      MDR1 gene encoding for P-glycoprotein (P-gp). RNA interference of MDR1 gene
      expression was used as a strategy to reverse MDR1-mediated multidrug resistance
      phenotypes. Here we report that endonuclease-prepared small interfering RNA
      (esiRNA) at concentrations as low as 10 ng/ml (about 0.7 nM) can decrease MDR1
      expression and increase chemosensitivity in the Adriamycin-induced resistant MCF
      7/R cells. When MCF-7/R cells were transiently transfected with esiRNA of MDR1
      (esiMDR1), the MDR1 mRNA was reduced by about 50%, drug accumulation increased by
      about 30%, and the IC50 for daunorubicin was reduced from 4.5 to 1.2 microM.
      These results provide evidence that esiRNA of MDR1 could be an alternative to P
      gp inhibitors with the advantage of avoiding non-specific suppression with a
      lower effective dosage than using a single siRNA duplex, offering a potential
      therapeutic application of siRNA.

PMID- 16564524
TI  - Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture.
AB  - An association has been previously established between uncompensated diabetes
      mellitus and the loss of bone mineral density and/or quality. In this study, we
      evaluated the effects of metformin on the growth and differentiation of
      osteoblasts in culture. Treatment of two osteoblast-like cells (UMR106 and
      MC3T3E1) with metformin (25-500 microM) for 24 h led to a dose-dependent increase
      of cell proliferation. Metformin also promoted osteoblastic differentiation: it
      increased type-I collagen production in both cell lines and stimulated alkaline
      phosphatase activity in MC3T3E1 osteoblasts. In addition, metformin markedly
      increased the formation of nodules of mineralization in 3-week MC3T3E1 cultures.
      Metformin induced activation and redistribution of phosphorylated extracellular
      signal-regulated kinase (P-ERK) in a transient manner, and dose-dependently
      stimulated the expression of endothelial and inducible nitric oxide synthases
      (e/iNOS). These results show for the first time a direct osteogenic effect of
      metformin on osteoblasts in culture, which could be mediated by
      activation/redistribution of ERK-1/2 and induction of e/iNOS.

PMID- 16564523
TI  - Involvement of Rho signaling in PAR2-mediated regulation of neutrophil adhesion
      to lung epithelial cells.
AB  - Protease-activated receptor 2 (PAR2) has been implicated in the pathogenesis of
      airway inflammation. We report that epithelial PAR2 stimulation with trypsin
      (0.05-1 U/ml) or an agonist peptide (SLIGKV-NH2, 1-100 microM) for 0.5-3 h dose-
      and time-dependently enhanced neutrophil adhesion to alveolar type II epithelial
      cells (A549 cells) and that this stimulation also induced the formation of
      epithelial actin filaments. Both responses in neutrophil adhesion and epithelial
      actin reorganization were reduced by a Rho inhibitor, mevastatin and by a Rho
      associated kinase (ROCK) inhibitor, Y-27632 ((R)-(+)-trans-N-(4-Pyridyl)-4-(1
      aminoethyl)-cyclohexanecarboxamide). Neutrophil adherence was also inhibited by
      an inhibitor of actin polymerization, cytochalasin D and a tyrosine kinase
      inhibitor, genistein. Further, the PAR2-mediated tyrosine phosphorylation of
      focal adhesion kinase (FAK), a major cytoskeleton protein, was detected, and this
      response was inhibited by mevastatin or Y-27632. These results suggest that PAR2
      stimulation of alveolar epithelial cells enhances neutrophil adhesion presumably
      at least in part through Rho/ROCK signal-mediated actin cytoskeleton
      reorganization associated with the tyrosine phosphorylation of FAK.

PMID- 16564525
TI  - Stimulation of human breast carcinoma cell invasiveness and urokinase plasminogen
      activator activity by glucose deprivation.
AB  - Glucose deprivation has been shown to increase the invasive and metastatic
      potential of tumour cells. In the present study, we determined whether the
      enhanced tumour cell invasiveness resulting from glucose deprivation is linked to
      increased activity of enzymes required for extracellular matrix degradation.
      Results of in vitro invasion assays revealed that the invasiveness of human MDA
      MB-231 and MCF-7 breast carcinoma cells and MCF-10A1 normal breast cells was,
      respectively, 3.9-, 2.9-, and 2.1-fold higher when they were incubated under
      glucose-deprivation (0.2 mM glucose) than when incubated under physiological
      blood glucose levels (5 mM). This effect of glucose deprivation on invasion
      correlated with increased urokinase plasminogen activator (uPA) and plasmin
      activity. Glucose deprivation did not increase the levels of gelatinase and
      plasminogen activator inhibitor-1 secretion, or the expression of cell-associated
      uPA receptor. To determine whether the increased invasiveness resulting from
      glucose deprivation is causally linked to increased uPA activity, invasion assays
      were conducted using MDA-MB-231 cells incubated in 0.2 mM or 5 mM glucose in the
      presence of a neutralising anti-uPA antibody. Results revealed that the anti-uPA
      antibody significantly inhibited invasion in a dose-dependent manner and to a
      much greater extent in cells incubated in 0.2 mM glucose than in cells incubated
      in 5 mM glucose. These results suggest that low glucose levels in malignant
      cancers increase tumour cell invasiveness by stimulating uPA and plasmin
      activity.

PMID- 16564526
TI  - Trypanosoma cruzi: infectivity modulation of a clone after passages through
      different hosts.
AB  - Although Trypanosoma cruzi virulence can be modified through passages in vivo or
      long-term in vitro culture, the mechanisms involved are poorly understood. Here
      we report modifications in the infectivity of a T. cruzi clone after passages in
      different hosts without detectable changes in parasite genetic patterns. A clone
      was obtained from a T. cruzi IIe isolate and showed to be less virulent than the
      original isolate (p<0.05). This clone was enzymatically similar to the original
      isolate as shown by multilocus enzyme electrophoresis. Infection of this clone
      was compared by successive passages in mice and guinea pigs. The mouse-passaged
      subline became more virulent for both host species compared to the guinea pig
      passaged subline (p<0.05). The clone line displayed similar random amplified
      polymorphic DNA patterns before and after passages in different hosts suggesting
      that alterations in virulence could be a result of a differential expression of
      virulence factors.

PMID- 16564527
TI  - Aggression, dominance, and affiliation: Their relationships with androgen levels
      and intelligence in 5-year-old children.
AB  - This study explores the potential relationship between social behavior
      (aggression, dominance, and affiliation) and testosterone, androstenedione, and
      DHEA measurements in 5-year-old children while also analyzing the moderating
      effect of IQ on the hormone-behavior relationship. 129 healthy normal Iberian
      children (60 boys and 69 girls) were videotaped in free play interactions in the
      school playground. Their behavior was then evaluated with particular emphasis on
      aggression, government, and affiliation. Testosterone, androstenedione, and DHEA
      levels were measured using an enzyme immunoassay technique in saliva samples. A
      test (K-BIT) which provides an IQ measurement for children was also administered
      to subjects. The correlation analysis revealed a positive relationship between
      the behavioral factor of Provocation and androstenedione in boys, and a
      regression analysis indicated that this relationship was moderated in a positive
      direction by the subject's intelligence. In girls, we observed a positive
      relationship between testosterone and Affectivity, with this relationship being
      moderated in a negative direction by intelligence.

PMID- 16564528
TI  - Expression of CD28 and cytotoxic T lymphocyte antigen 4 at the maternal-fetal
      interface in women with unexplained pregnancy loss.
AB  - OBJECTIVE: To investigate the expression of CD28 and CTLA-4, two costimulatory
      molecules involved in T-cell activation at the maternal-fetal interface in women
      with unexplained pregnancy loss. METHODS: A total of 57 women, 39 with
      unexplained spontaneous abortion (SA) and 18 with unexplained recurrent
      spontaneous abortion (RSA), were enrolled in the study. A high-resolution
      spectratyping analysis of fluorescent bands was performed to detect CD28 and CTLA
      4 expression in decidual tissues. RESULTS: The mean expression of CTLA-4 mRNA was
      significantly higher in women with SA than in controls (P<0.05). Moreover, the
      expression of CTLA-4 was higher in SA patients with genotype AA and phenotype A+
      (AA+AG) than in controls (P<0.01). The expression of CTLA-4 was not significantly
      different in patients with RSA and in controls. The expression of CD28 was
      significantly decreased in patients with RSA (P<0.01) and SA (P<0.05) compared
      with controls. The mean ratios of CTLA-4/CD28 were significantly higher in
      patients with RSA (P<0.01) and SA (P<0.05) than in controls. CONCLUSIONS: This
      study suggests that an imbalance in CTLA-4/CD28 expression or suppressed T-cell
      activity at the maternal-fetal interface may confer susceptibility to unexplained
      pregnancy loss.

PMID- 16564529
TI  - Lymphocyte resistance to lysophosphatidylcholine mediated apoptosis in
      atherosclerosis.
AB  - OBJECTIVE: Apoptosis is being increasingly regarded as a key component in the
      development and progression of atherosclerosis. Since it has become apparent that
      the immune system plays a predominant role in mediating atherogenesis, there has
      been a growing recognition that the evaluation of lymphocyte apoptosis may
      contribute to understanding a persistent altered immune and inflammatory
      response. The aim of the present study was to evaluate the apoptotic effect of
      lysophosphatidylcholine (LPC) on peripheral blood lymphocytes (PBL) derived from
      unstable angina (UA) patients, as compared to healthy donors. METHODS: PBL
      isolated from 27 healthy donors and 25 age matched UA patients were examined.
      Early apoptotic events induced by LPC in resting and phytohemagglutinin (PHA)
      activated lymphocytes were evaluated by several apoptotic assays. The levels of
      intracellular reactive oxygen species (ROS) and the expression of apoptotic
      regulated proteins (Bcl-2 and Bax) were measured. RESULTS: LPC was found to
      induce apoptosis in normal activated lymphocytes, in a dose- and time-dependent
      manner, in association with an increase in intracellular ROS. In UA patients, an
      exposure of PHA-activated PBL to LPC triggered neither an increase in ROS
      generation, nor in the apoptotic manifestations, and was associated with a
      significantly lower ratio of Bax/Bcl-2 expression. CONCLUSION: Our results
      indicate that PBL isolated from UA patients may be resistant to apoptosis
      induction by LPC, resulting from oxidative stress challenge and dysregulation of
      apoptosis-related protein expression.

PMID- 16564530
TI  - Preparative isolation and purification of chemical constituents from the root of
      Polygonum multiflorum by high-speed counter-current chromatography.
AB  - High-speed counter-current chromatography methods, combined with solvent
      partition, were applied to the systematic separation and purification of chemical
      components from Chinese medicinal herb Polygonum multiflorum extract. The aim of
      this paper is summing up the rules of solvent system selection for diverse
      fractions of herbal extract, and establishing the systematic pattern to screen
      the bioactive constituents rapidly. Nine compounds including emodin,
      chrysophanol, rhein, 6-OH-emodin, emodin-8-beta-D-glucoside, polygonimitin B,
      2,3,5,4'-tetrahydroxystilbene-2-beta-D-glucoside, gallic acid and an unknown
      glycoside, which differed in quantity and polarity remarkably, were obtained. The
      purities of them were all above 97% as determined by high-performance liquid
      chromatography (HPLC), and their structures were identified by 1H NMR and
      electrospray ionization mass spectrometry (ESI-MS). The results demonstrated that
      HSCCC is a speedy and efficient technique for systematic isolation of bioactive
      components from traditional medicinal herbs.

PMID- 16564532
TI  - Anisotropic siloxane-based monolith prepared in confined spaces.
AB  - When bicontinuous gels are prepared via sol-gel method in a 2-dimensionally (2D)
      confined space, the gel skeletons in the vicinity of interface of a mold are
      elongated perpendicular to the interface. This phenomenon was attributed to the
      dynamic wetting of polymerizing siloxane phase onto the interface of the mold
      under gravity. In this paper, we report the successful preparation of monolithic
      columns with an oriented pillar structure in a variety of 2D confined spaces.
      Starting from a solution, which consists of methyltrimethoxysilane (MTMS), the
      macroporous structure is prepared in situ by a completely spontaneous process. In
      the oriented pillar structure, bicontinuous siloxane skeletons deformed or
      disappeared and most pillars are oriented along the direction of gravity. Gel
      morphologies with the pillar structure were examined by scanning electron
      microscopy (SEM) and laser scanning confocal microscopy (LSCM). Geometrical
      information on gel morphologies was numerically derived from the obtained 3D LSCM
      images.

PMID- 16564531
TI  - Insights into the retention mechanism on an octadecylsiloxane-bonded silica
      stationary phase (HyPURITY C18) in reversed-phase liquid chromatography.
AB  - Plots of the retention factor against mobile phase composition were used to
      organize a varied group of solutes into three categories according to their
      retention mechanism on an octadecylsiloxane-bonded silica stationary phase
      HyPURITY C18 with methanol-water and acetonitrile-water mobile phase compositions
      containing 10-70% (v/v) organic solvent. The solutes in category 1 could be fit
      to a general retention model, Eq. (2), and exhibited normal retention behavior
      for the full composition range. The solutes in category 2 exhibited normal
      retention behavior at high organic solvent composition with a discontinuity at
      low organic solvent compositions. The solutes in category 3 exhibited a
      pronounced step or plateau in the middle region of the retention plots with a
      retention mechanism similar to category 1 solutes at mobile phase compositions
      after the discontinuity and a different retention mechanism before the
      discontinuity. Selecting solutes and appropriate composition ranges from the
      three categories where a single retention mechanism was operative allowed
      modeling of the experimental retention factors using the solvation parameter
      model. These models were then used to predict retention factors for solutes not
      included in the models. The overwhelming number of residual values [log k
      (experimental) - log k (model predicted)] were negative and could be explained by
      contributions from steric repulsion, defined as the inability of the solute to
      insert itself fully into the stationary phase because of its bulkiness (i.e.,
      volume and/or shape). Steric repulsion is shown to strongly depend on the mobile
      phase composition and was more significant for mobile phases with a low volume
      fraction of organic solvent in general and for mobile phases containing methanol
      rather than acetonitrile. For mobile phases containing less than about 20 % (v/v)
      organic solvent the mobile phase was unable to completely wet the stationary
      phase resulting in a significant change in the phase ratio and for acetonitrile
      (but less so methanol) changes in the solvation environment indicated by a
      discontinuity in the system maps.

PMID- 16564533
TI  - Use of ultra-performance liquid chromatography in pharmaceutical development.
AB  - Ultra-performance liquid chromatography (UPLC) has been investigated as an
      alternative to HPLC for the analysis of pharmaceutical development compounds. We
      present data on three compounds showing that significant reductions in separation
      time can be achieved without compromising the separation quality. Results from
      precision and comparative studies indicate that UPLC is a suitable technique for
      routine pharmaceutical analysis.

PMID- 16564535
TI  - Structural organization of cetyltrimethylammonium sulfate in aqueous solution:
      The effect of Na2SO4.
AB  - We used dynamic light scattering (DLS), steady-state fluorescence, time resolved
      fluorescence quenching (TRFQ), tensiometry, conductimetry, and isothermal
      titration calorimetry (ITC) to investigate the self-assembly of the cationic
      surfactant cetyltrimethylammonium sulfate (CTAS) in aqueous solution, which has
      SO(2-)4 as divalent counterion. We obtained the critical micelle concentration
      (cmc), aggregation number (N(agg)), area per monomer (a0), hydrodynamic radius
      (R(H)), and degree of counterion dissociation (alpha) of CTAS micelles in the
      absence and presence of up to 1 M Na2SO4 and at temperatures of 25 and 40 degrees
      C. Between 0.01 and 0.3 M salt the hydrodynamic radius of CTAS micelle R(H)
      approximately 16 A is roughly independent on Na2SO4 concentration; below and
      above this concentration range R(H) increases steeply with the salt
      concentration, indicating micelle structure transition, from spherical to rod
      like structures. R(H) increases only slightly as temperature increases from 25 to
      40 degrees C, and the cmc decreases initially very steeply with Na2SO4
      concentration up to about 10 mM, and thereafter it is constant. The area per
      surfactant at the water/air interface, a0, initially increases steeply with
      Na2SO4 concentration, and then decreases above ca. 10 mM. Conductimetry gives
      alpha = 0.18 for the degree of counterion dissociation, and N(agg) obtained by
      fluorescence methods increases with surfactant concentration but it is roughly
      independent of up to 80 mM salt. The ITC data yield cmc of 0.22 mM in water, and
      the calculated enthalpy change of micelle formation, Delta H(mic) = 3.8 kJ mol(
      1), Gibbs free energy of micellization of surfactant molecules, Delta G(mic) = 
      38.0 kJ mol(-1) and entropy TDelta S(mic) = 41.7 kJ mol(-1) indicate that the
      formation of CTAS micelles is entropy-driven.

PMID- 16564534
TI  - Layer-by-layer assembly of mucin and chitosan--Influence of surface properties,
      concentration and type of mucin.
AB  - Bovine submaxillary mucin (BSM) and chitosan were used to build layer-by-layer
      structures on solid substrates. The build-up was monitored using in situ
      ellipsometry to obtain time resolved values of the thickness and adsorbed amount.
      Additionally surface morphology during build-up was studied by atomic force
      microscopy (AFM). It was found that the adsorbed amount of the film increases
      approximately linearly with each deposition cycle on hydrophobized silica whereas
      construction on silica was found not to be possible at the experimental
      conditions used. We conclude that sufficient amount of the first mucin layer is
      crucial for the subsequent multilayer formation. The complex build-up kinetics on
      hydrophobized silica is characterized by adsorption and redissolution processes
      and the overall growth is the sum of both processes. AFM imaging on hydrophobized
      silica also confirmed the presence of redissolution processes and chitosan
      addition led to a reduction both in the number of surface aggregates and in the
      roughness of the surface. The present work also shows that by adjusting the
      relative concentrations of the polyelectrolytes it is possible to change the
      growth rate considerably. The final structures after deposition of 8 bilayers
      were found to have a high content of water and film stability test revealed that
      a substantial amount dissolves when increasing electrolyte concentration or pH of
      the ambient solution. Human mucin from saliva (MUC5B) was also used to create
      multilayers with chitosan on hydrophobized silica and it was revealed that no
      redissolution appears to be present in this system.

PMID- 16564536
TI  - Comprehensive analysis of monoclonal antibodies against detergent-insoluble
      membrane/lipid rafts of HL60 cells.
AB  - Glycosphingolipids and cholesterol are principal components of plasmamembrane
      microdomains, i.e. lipid rafts. Recent studies revealed the possible presence of
      a variety of microdomains that distinctly differ in terms of their molecular
      composition and functions. To understand their precise structures and functions,
      we produced monoclonal antibodies (MAbs) by immunizing mice to the microdomains
      prepared from a fraction of detergent-insoluble membrane (DIM) of HL60 cells.
      Biochemical characterization of the antigen epitopes led to classification of the
      MAbs into two groups. One group consists of MAbs that react with lipids such as
      phosphatidylglucoside, lysophosphatidylinositol, and gangliosides (GM1a and
      GD1b), and the other consists of MAbs that react with proteins such as annexin I,
      aminopeptidase N and acrogranin. Immunofluorescence staining of HL60 cells with
      the MAbs, except for the MAbs that recognize lysophosphatidylinositol or annexin
      I, resulted in patchy-like images of the cell membranes. Interestingly, MAbs
      belonging to the former group had the potential to induce cell
      proliferation/differentiation in vitro. Our MAbs against the DIM fraction of HL60
      cells can be valuable tools for the study of membrane microdomains.

PMID- 16564537
TI  - Ecological characterization of Steinernema anatoliense (Rhabditida:
      Steinernematidae).
AB  - Our study describes the basic ecological characteristics of the entomopathogenic
      nematode Steinernema anatoliense including its response to temperature, moisture,
      and host range. The effect of temperature and soil moisture on the infection of
      Galleria mellonella larvae by S. anatoliense was determined. The temperature
      range for infectivity was greater than that for development. The optimal
      temperature for infection and development was 25 degrees C. Although S.
      anatoliense infected the hosts at 10 degrees C, no reproduction occurred at this
      temperature. This nematode species that was isolated from a cold region of Turkey
      exhibited warm-adapted temperature characteristics. Optimum water content of the
      soil for S. anatoliense to infect the host was 10%.

PMID- 16564538
TI  - The mechanism of iron release from the transferrin-receptor 1 adduct.
AB  - We report the determination in cell-free assays of the mechanism of iron release
      from the N-lobe and C-lobe of human serum transferrin in interaction with intact
      transferrin receptor 1 at 4.3< or =pH< or =6.5. Iron is first released from the N
      lobe in the tens of milliseconds range and then from the C-lobe in the hundreds
      of seconds range. In both cases, iron loss is rate-controlled by slow proton
      transfers, rate constant for the N-lobe k(1)=1.20(+/-0.05)x10(6)M(-1)s(-1) and
      for the C-lobe k(2)=1.6(+/-0.1)x10(3)M(-1)s(-1). This iron loss is subsequent to
      a fast proton-driven decarbonation and is followed by two proton gains,
      (pK(1a))/2=5.28 per proton for the N-lobe and (pK(2a))/2=5.10 per proton for the
      C-lobe. Under similar experimental conditions, iron loss is about 17-fold faster
      from the N-lobe and is at least 200-fold faster from the C-lobe when compared to
      holotransferrin in the absence of receptor 1. After iron release, the
      apotransferrin-receptor adduct undergoes a slow partial dissociation controlled
      by a change in the conformation of the receptor; rate constant k(3)=1.7(+/
      0.1)x10(-3)s(-1). At endosomic pH, the final equilibrated state is attained in
      about 1000 s, after which the free apotransferrin, two prototropic species of the
      acidic form of the receptor and apotransferrin interacting with the receptor
      coexist simultaneously. However, since recycling of the vesicle containing the
      receptor to the cell surface takes a few minutes, the major part of transferrin
      will still be forwarded to the biological fluid in the form of the apotransferrin
      receptor protein-protein adduct.

PMID- 16564539
TI  - Evolutionary relationship between initial enzymes of tetrapyrrole biosynthesis.
AB  - Glutamate-1-semialdehyde 2,1-aminomutase (GSAM) is the second enzyme in the C(5)
      pathway of tetrapyrrole biosynthesis found in most bacteria, in archaea and in
      plants. It catalyzes the transamination of glutamate-1-semialdehyde to 5
      aminolevulinic acid (ALA) in a pyridoxal 5'-phosphate (PLP)-dependent manner. We
      present the crystal structure of GSAM from the thermophilic cyanobacterium
      Thermosynechococcus elongatus (GSAM(Tel)) in its PLP-bound form at 2.85A
      resolution. GSAM(Tel) is a symmetric homodimer, whereas GSAM from Synechococcus
      (GSAM(Syn)) has been described as asymmetric. The symmetry of GSAM(Tel) thus
      challenges the previously proposed negative cooperativity between monomers of
      this enzyme. Furthermore, GSAM(Tel) reveals an extensive flexible region at the
      interface of the proposed complex of GSAM with glutamyl-tRNA reductase (GluTR),
      the preceding enzyme in tetrapyrrole biosynthesis. Compared to GSAM(Syn), the
      monomers of GSAM(Tel) are rotated away from each other along the dimerization
      interface by 10 degrees . The associated flexibility of GSAM may be essential for
      complex formation with GluTR to occur. Unexpectedly, we find that GSAM is
      structurally related to 5-aminolevulinate synthase (ALAS), the ALA-producing
      enzyme in the Shemin pathway of alpha-proteobacteria and non-plant eukaryotes.
      This structural relationship applies also to the corresponding subfamilies of PLP
      dependent enzymes. We thus propose that the CoA-subfamily (including ALAS) and
      the aminotransferase subfamily II (including GSAM) are evolutionarily closely
      related and that ALAS may thus have evolved from GSAM.

PMID- 16564540
TI  - A novel method to detect functional microRNA targets.
AB  - MicroRNA (miRNA) molecules are non-coding RNAs, 19 to 24 nt in length that have
      been identified recently as important regulators of gene expression. Several
      computational methods have been developed to describe the target recognition
      mechanism by miRNA. We propose here a novel method to detect miRNA-mRNA complexes
      in eukaryotic cells. As a first step, we synthesize cDNA on an mRNA template
      using miRNAs as the endogenous cytoplasmic primer. This step extends miRNA and
      overcomes the problem of low complementary binding of miRNAs to their targets.
      Purified hybrid 3'-cDNA-miRNA-5' molecules are used in a second round of reverse
      transcription to anneal to target mRNA in a highly gene-specific manner. The 5'
      end analysis of these cDNA molecules demonstrated that primers for cDNAs were
      "signatures" of miRNA molecules, and over-expression of their full-length mature
      miRNAs resulted in functional inhibition of target protein expression.

PMID- 16564541
TI  - Graduated driver licensing and teenage driver research in 2006.
AB  - This is the third update of research on graduated driver licensing (GDL) and
      related teenage driver issues. It briefly summarizes research published since or
      not included in the 2005 update (Hedlund, J., & Compton, R. (2005). Graduated
      driver licensing research in 2004 and 2005. Journal of Safety Research, 36(2),
      109-119.), describes research in progress of which the authors are aware, and
      announces plans for a symposium on teenage driving and GDL to be held in February
      2007.

PMID- 16564542
TI  - Challenges confronting female surgical leaders: overcoming the barriers.
AB  - BACKGROUND: The number of women reaching top ranks in academic surgery is
      remarkably low. The purpose of this study was to identify: 1) barriers to
      becoming a female surgical leader; 2) key attributes that enable advancement and
      success; and 3) current leadership challenges faced as senior leaders. METHODS:
      Semi-structured interviews of ten female surgical leaders queried the following
      dimensions: attributes for success, lessons learned, mistakes, key career steps,
      the role of mentoring, gender advantages/disadvantages, and challenges. RESULTS:
      Perseverance (60%) and drive (50%) were identified as critical success factors,
      as were good communication skills, a passion for scholarship, a stable home life
      and a positive outlook. Eighty percent identified discrimination or gender
      prejudice as a major obstacle in their careers. While 90% percent had mentors,
      50% acknowledged that they had not been effectively mentored. Career advice
      included: develop broad career goals (50%); select a conducive environment (30%);
      find a mentor (60%); take personal responsibility (40%); organize time and
      achieve balance (40%); network (30%); create a niche (30%); pursue research
      (30%); publish (50%); speak in public (30%); and enjoy the process (30%). Being
      in a minority, being highly visible and being collaborative were identified as
      advantages. Obtaining buy-in and achieving consensus was the greatest leadership
      challenge reported. CONCLUSIONS: Female academic surgeons face challenges to
      career advancement. While these barriers are real, they can be overcome by
      resolve, commitment, and developing strong communication skills. These elements
      should be taken into consideration in designing career development programs for
      junior female surgical faculty.

PMID- 16564543
TI  - The effect of anchoring suture on the anastomotic blood flow in a rat model of
      human esophagojejunostomy.
AB  - PURPOSE: An impairment of anastomotic blood flow (ABF) and the resulting hypoxia
      readily lead to the complications such as leakage and stricture. We performed an
      animal study to evaluate the effect of anchoring suture for minimizing the
      impairment of ABF caused by tensile loading. MATERIALS AND METHODS: An end-to
      side jejunojejunostomy was done in 20 rats, and this followed the modeling of a
      human end-to-side esophagojejunostomy. Laser Doppler flowmetry was checked in
      three different tensile conditions to evaluate the influence of anchoring suture
      on the ABF. RESULTS: Before anchoring suture, the mean ABF was 129.06 perfusion
      unit (PU), 96.99 PU, and 69.04 PU, in the order of tensile stress. After
      anchoring suture, the mean ABF was 121.68, 103.30, and 87.06 PU (P < 0.01).
      CONCLUSION: Anchoring suture is a novel method to reduce the impairment of the
      anastomotic blood flow that is caused by tension.

PMID- 16564544
TI  - Does anti-oxidant prophylaxis with melatonin prevent adverse outcomes related to
      increased oxidative stress caused by laparoscopy in experimental rat model?
AB  - BACKGROUND: We hypothesized that prophylaxis with an anti-oxidant should prevent
      potential adverse outcomes of laparoscopy related to increased oxidative stress
      in splanchnic organs, including small intestine, liver, and kidneys, and
      melatonin is the most appropriate agent for this purpose. METHODS: Twenty-four
      Sprague-Dawley rats weighing 300 to 350 g were allocated randomly into three
      groups consisting of eight in each as follows: Group I: gasless (control); group
      II: 15 mmHg intraabdominal pressure (IAP) with CO2 pneumoperitoneum for 60 min;
      group III: 15 mmHg IAP with CO2 pneumoperitoneum for 60 min, and melatonin (10
      mg/kg) was administered at two occasions, 5 min before insufflation and
      immediately before the desufflation. In group II and III, rats left resting for
      30 min after abdominal deflation, the small intestine (terminal ileum), liver and
      kidney examples were excised from same locations. The specimens were also
      obtained using the same time points in group I rats, comprising the control
      group. The specimens were immediately placed at -80 degrees C for the
      malondialdehyde (MDA) measurements. In addition, segments of terminal ileum were
      taken from the similar places in all of the animals for the histological
      examinations. RESULTS: Comparisons among the groups revealed that highest mean
      MDA levels in liver, small intestine and kidney were in the group II, followed by
      the group III and control group. There was significant difference between mean
      MDA levels in small intestine, liver and kidney of group II and III (P < 0.0005).
      However, no significant difference was found between mean MDA levels in small
      intestine, liver, and kidney of the group III and control group. Mucosa and
      submucosa were affected significantly in 15 mmHg IAP group (no prophylaxis) when
      compared with the control and melatonin prophylaxis groups (P = 0.002). However,
      there was not a significant difference in mean damage score of mucosa, submucosa,
      and muscular layers in control group when compared to melatonin prophylaxis
      group. CONCLUSIONS: This experimental study indicated that melatonin prophylaxis,
      with anti-oxidant and anti-inflammatory actions, may have an important role in
      the prevention of potential complications related to oxidative stress injury on
      splanchnic organs induced by laparoscopy.

PMID- 16564545
TI  - Angiotensin II receptor expression following intestinal transplantation in mice.
AB  - BACKGROUND: To further improve the success rate of intestinal transplantation
      there is a need to find early appearing indicators of rejection. The specific aim
      of this study was to compare Angiotensin (Ang) II type 1 receptor and Ang II type
      2 receptor expression in relation to histological signs of rejection. METHODS:
      Mice of the C57BL6 strain with syngeneic intestinal grafts were compared to mice
      subjected to allogeneic intestinal transplantation with BalbC strain as donors.
      Local expression of Ang II type 1 and 2 receptor was evaluated using rt-PCR and
      Western blot and compared to histological picture in grafts and native intestine.
      RESULTS: The Ang II type 2 receptor protein expression was markedly up-regulated
      in the allogeneically transplanted graft from day 1 postoperatively. Histological
      signs of rejection were not seen until day 6. CONCLUSION: Intestinal allograft
      transplantation in mice is associated with a marked up-regulation of the Ang II
      type 2 receptor. However, the detailed role of the renin-angiotensin system in
      the immune rejection following intestinal transplantation remains to be
      clarified.

PMID- 16564546
TI  - Recovery of hepatic function determined by cytochrome P450-dependent drug
      metabolism lags after compensatory hepatic volume changes after portal vein
      ligation in rats.
AB  - BACKGROUND: Clinically, portal vein embolization has been proven to be useful as
      a preoperative treatment for major hepatic surgeries with impaired liver
      function. However, its effects on the metabolism and elimination of various drugs
      after portal vein embolization or ligation remain to be elucidated. MATERIALS AND
      METHODS: A portal vein branch that perfuses the central and left lobes of the
      liver of male Wistar rat was ligated, and changes in the weights of ligated and
      nonligated lobules as well as hepatic levels and activities of cytochrome P450
      (CYP) isoforms, such as CYP3A2 and CYP2C11, were determined. To evaluate in vivo
      the effect of PVL on hepatic drug metabolism, the narcotic activity (sleep time)
      of midazolam, a specific substrate for CYP3A2, was measured. RESULTS: Although
      plasma levels of alanine aminotransferase and hepatic weight returned to basal
      levels at day 7 after the portal vein ligation, hepatic activities of CYP3A2 and
      CYP2C11 still remained low (53% and 54% of control levels, respectively), and
      returned to their initial levels after about day 14. The metabolism of midazolam
      was prolonged by approximately three times at day 7 after ligation and returned
      to basal levels at day 14. CONCLUSIONS: Because hepatic CYP-dependent drug
      metabolism by CYP isoforms recovered more slowly than the apparent recovery of
      hepatic volume and plasma alanine aminotransferase levels, the therapeutics of
      drugs metabolized by the CYP isoforms should be used carefully in patients who
      receive major hepatectomy with portal vein branch embolization.

PMID- 16564547
TI  - Differential transcriptional responses of keloid and normal keratinocytes to
      serum stimulation.
AB  - BACKGROUND: Keloids are benign tumors that occur only in response to injury, for
      which there is no effective treatment. We demonstrated previously that keloid
      keratinocytes (KKs) promote fibroblast proliferation more than normal
      keratinocytes (NKs) and that transforming growth factor (TGF)-beta is a component
      of that signal. We used the transcriptional response to serum stimulation to
      examine how TGF-beta expression is stimulated in KKs. MATERIALS AND METHODS:
      Quiescent KKs and NKs were stimulated using serum; harvested using RNA at 0, 1,
      6, 12, and 24 h; and analyzed using quantitative real-time polymerase chain
      reaction. TGF-beta activity in the conditioned medium was measured with an
      MLEC/PAI-luciferase assay. Inhibition of ERK1/2, p38 kinase, and JNK pathways was
      performed with PD98059, SB203580, and SP600125, respectively. RESULTS: Increased
      transcription of TGF-beta2 occurs within 1 h of serum stimulation in KKs but not
      in NKs. In contrast, TGF-beta3 transcription was suppressed in KKs compared with
      NKs. No significant differences were observed in the transcriptional response of
      TGF-beta1. Increased TGF-beta2 mRNA correlated with increased TGF-beta biological
      activity in the conditioned medium. Inhibition of the ERK, p38 kinase or JNK
      signal transduction pathways blocked the transcriptional up-regulation of TGF
      beta2, TbetaR1, and TbetaR2 in KKs. CONCLUSIONS: KKs produce more TGF-beta2 mRNA
      than NKs in response to serum stimulation, resulting in increased TGF-beta
      activity in conditioned medium. Combining these results with our previous data
      lead us to propose a model of keloid formation characterized by an exaggerated
      response to cellular stress and abnormal epithelial-mesenchymal signaling
      promoting keloid formation.

PMID- 16564548
TI  - Postconditioning in females depends on injury severity.
AB  - BACKGROUND: Postconditioning, a series of brief ischemia/reperfusion (I/R) cycles
      at reperfusion onset, is a recently described novel approach to attenuate I/R
      injury, and because it is an after-injury treatment strategy, it may have greater
      clinical potential than preconditioning. However, it has not been determined
      whether postconditioning is effective in women. MATERIALS AND METHODS: Adult male
      and female (250-300 g) Sprague-Dawley rat hearts (n = 25) were isolated, perfused
      via Langendorff model, and subjected to 15 min of equilibration, 20 or 25 min of
      global index ischemia (37 degrees C), and 40 min total reperfusion.
      Postconditioned hearts were subjected to 6 cycles of 10-s reperfusion/10-s
      ischemia immediately after release of the global index ischemia. Hearts were
      assigned randomly to one of four groups: 1) control hearts, 20 min index
      ischemia; 2) postconditioned hearts, 20 min index ischemia; 3) control hearts, 25
      min index ischemia; or 4) postconditioned hearts, 25 min index ischemia. All data
      are reported as mean +/- SEM and were analyzed with unpaired student's t test; P
      < 0.05 considered significant. RESULTS: Postconditioning in female rats after 20
      min of ischemia reduced depression of left ventricular-developed pressure (93.9
      +/- 6.7% postconditioning recovery versus 58.6 +/- 12.6% control recovery, P <
      0.05), attenuated the increase of end-diastolic pressure (P < 0.05), and reduced
      the depression of +dP/dT and -dP/dT (P < 0.05). The postconditioning protective
      effect disappeared in female rats exposed to 25 min of ischemia. The
      postconditioning protective effect was observed in male rats after both 20 min
      and 25 min ischemia. CONCLUSIONS: Postconditioning confers cardioprotection in
      leukocyte-free, buffer-perfused female hearts, but this protection may depend on
      ischemia duration. The attractive potential for the clinical application of
      postconditioning, however, warrants further studies to elucidate the mechanistic
      pathways and differences in males and female rats.

PMID- 16564549
TI  - Cilostazol suppresses adhesion of human neutrophils to HUVECs stimulated by FMLP
      and its mechanisms.
AB  - The interaction between neutrophils and endothelial cells (ECs) is of great
      importance in many physiological and pathological progresses. Although cilostazol
      (CLZ), a novel selective phosphodiesterase (PDE) type 3 inhibitor, has been
      proved to be useful in vasodilatation and inhibition of platelet aggregation, its
      effect on adhesion is not clearly known. In this study, we examined the effects
      and investigated the mechanisms of cilostazol on neutrophil adhesion to human
      umbilical endothelial cells (HUVECs) triggered by N-formyl-methionyl-leucyl
      phenylal-anine (FMLP), a chemotactic peptide. The soluble vascular cell adhesive
      molecule-1 (sVCAM-1) release from FMLP (10 microM)-stimulated HUVECs was
      determined by ELISA kits. Fluo-2, a fluorescent indicator, was used to
      investigate intracellular free calcium concentration ([Ca2+]i) in HUVECs. HL-60
      cells were induced to be neutrophilic by DMSO and loaded with Fluo-3, another
      fluorescent indicator, to detect [Ca2+]i, and CLA was used as a chemiluminescent
      indicator to determine superoxide production in neutrophilic cells. The result
      showed that CLZ (1-100 microM) significantly inhibited neutrophil adhesion to
      FMLP-stimulated HUVECs. In HUVECs, CLZ obviously downregulated sVCAM-1 level,
      while it had no meaningful influence [Ca2)]i. But in neutrophils, FMLP-activated
      superoxide generation and [Ca2+]i increase were found being inhibited by exposure
      to CLZ . Furthermore, we also demonstrated that Ca2+ increase was preceded to the
      superoxide generation in neutrophils. The results suggest that CLZ involves in
      adhesion reactions between neutrophil and ECs, partly via VCAM-1 expression in
      ECs, and decreasing [Ca2+]i induced activation of neutrophils, which means a lot
      to prevent atherosclerosis and other cardiovascular diseases.

PMID- 16564550
TI  - Influence of anxiety on the production of oral volatile sulfur compounds.
AB  - Since many patients complain about halitosis without there being any clinical
      evidence of its cause, psychological symptoms have been pointed out as halitosis
      inducing factors. The aim of this study was to evaluate the influence of anxiety
      on the production of volatile sulfur compounds (VSC). Seventeen undergraduate men
      in good oral and general health participated in this study, after approval by the
      ethics committee. The volunteers were requested to refrain from toothbrushing,
      using mouth rinse and eating on the experimental day. Before presenting the
      anxiogenic condition, the volunteer was asked to fill out the Beck Anxiety
      Inventory questionnaire, to check whether he had been exposed to stressors during
      the previous week. The Video-Recorded Stroop Color-Word Test (VRSCWT) was used to
      elicit anxiety. The VSC (halimeter), blood pressure, heart rate and salivary flow
      measurements were taken before and after the VRSCWT. The volunteers presented a
      minimal or slight level of anxiety before the test. There was an increase in the
      oral concentration of VSC, Systolic Blood Pressure and of heart rate (p < 0.05)
      after the VRSCWT, and no changes in the salivary flow. The results of the present
      study showed that the anxiogenic condition (VRSCWT) induced increases in VSC
      concentration, which might contribute to halitosis.

PMID- 16564551
TI  - Preclinical pharmacokinetics and tissue distribution of a natural
      cardioprotective agent astragaloside IV in rats and dogs.
AB  - Astragaloside IV, a natural product purified from the Chinese medical herb
      Astragalus membranaceus (Fisch) Bge, is now being developed as a cardioprotective
      agent for treating cardiovascular diseases. The purpose of the present study was
      to examine in vivo pharmacokinetics and tissue distribution in both rats and dogs
      by using an established high-performance liquid chromatography (HPLC) coupled
      with tandem mass spectrometry quantitative detection method. Astragaloside IV
      showed moderate to fast elimination; the elimination half-life of astragaloside
      IV was 98.1, 67.2 and 71.8 min in male rats, and 34.0, 66.9 and 131.6 min in
      female rats at doses of 0.75, 1.5 and 3.0 mg/kg, respectively. There was no
      significant difference in systemic clearance at three dose levels, suggesting
      that astragaloside IV may have linear pharmacokinetic characteristics in rats
      within the dose ranges tested. The highest concentration of astragaloside IV was
      detected in the lung and liver. However, limited distribution to the brain,
      indicates that astragaloside IV may have difficulty penetrating the blood brain
      barrier. In addition, only about 50% of the parent astragaloside IV was recovered
      in both urine and feces. These results indicate that there was about 83%
      astragaloside IV binding to plasma protein and that the binding to the plasma is
      linear at the concentration range of 250-1000 ng/ml. As in rats, astragaloside IV
      may have linear pharmacokinetic characteristics in dogs within the dose ranges
      tested. Astragaloside IV was slowly cleared via hepatic clearance with a systemic
      clearance (CL) of about 0.004 l/kg/min. Based on the favorable pharmacokinetic
      properties in both rats and dogs, astragaloside IV warrants further investigation
      for the prevention of cardiovascular diseases.

PMID- 16564552
TI  - L-NAME pre-treatment partially inhibits the agmatine-evoked depression of the
      electrically induced twitch contraction of isolated rat vas deferens.
AB  - The effect of the putative endogenous ligand for alpha(2)-adrenoceptors and
      imidazoline receptors agmatine was studied in sympathetic neurotransmission in
      the rat epididymal vas deferens. Tissues were obtained from N(varpi)-nitro-l
      arginine methyl ester (l-NAME)-treated or normal animals and were contracted by
      electrical stimulation or by exogenous adenosine 5'-triphosphate (ATP). In the
      electrically stimulated epididymal end, agmatine produced an inhibitory effect on
      twitch contraction that was partially reversed in l-NAME-treated animals, whereas
      the inhibition produced by clonidine was not affected by l-NAME treatment. The
      nitric oxide (NO)-donor S-nitroso-N-acetyl-penicillamine (SNAP) also inhibited
      twitch contraction. Neither agmatine nor SNAP interfered with the responses
      induced by exogenous ATP in the epididymal end. Removal of the epithelium of the
      preparation did not modify the agmatine response. We conclude that a nitrergic
      pathway activated by agmatine plays a role in its inhibitory effect in rat vas
      deferens, but it remains to be investigated whether it results from a direct
      action on the enzyme NO-synthase or a receptor-mediated mechanism.

PMID- 16564553
TI  - (+)-Catechin prevents ultraviolet B-induced human keratinocyte death via
      inhibition of JNK phosphorylation.
AB  - High levels of (+)-catechin are found in the skin and seed of many fruits such as
      apples and grapes. Dietary supplementation with (+)-catechin has been
      demonstrated to protect epidermal cells against damage induced by ultraviolet B
      (UVB) radiation. However, the underlying mechanisms are not well understood yet.
      To determine whether (+)-catechin protects keratinocytes from UVB-induced damage,
      the viability of UVB- and H2O2-treated cells was determined by cell viability
      assay. Intracellular H2O2 level was measured by flow cytometry. UVB- or H2O2
      induced signaling pathways were detected by Western blotting. The results
      indicated that (+)-catechin inhibited UVB- and H2O2-induced keratinocyte death.
      In parallel, intracellular H2O2 generation in keratinocytes irradiated by UVB was
      inhibited by (+)-catechin in a concentration-dependent manner. (+)-Catechin also
      inhibited UVB- and H2O2-induced JNK activation in keratinocytes. However, it had
      little inhibitory effect on UVB- and H2O2-induced ERK and p38 activation even at
      a higher concentration, suggesting indirectly that JNK activation is required for
      the induction of apoptosis in keratinocytes exposed to UVB. Finally, we compared
      the cytotoxicity of (+)-catechin and (-)-epigallocatechin-3-gallate (EGCG) on
      keratinocytes. Cell viability assay showed that (+)-catechin was relatively
      nontoxic at higher doses. Taken together, our results demonstrate that (+)
      catechin inhibits UVB- and oxidative stress-induced H2O2 production and JNK
      activation and enhances human keratinocyte survival. However, although it seems
      that (+)-catechin and EGCG are equally effective in preventing keratinocyte
      death, (+)-catechin is relatively nontoxic and thus is suitable for developing as
      an anti-ageing agent for skin care.

PMID- 16564554
TI  - Expression of synaptopodin and GLEPP1 as markers of steroid responsiveness in
      primary focal segmental glomerulosclerosis.
AB  - The crucial involvement of podocyte failure in the development of hereditary
      focal segmental glomerulosclerosis (FSGS) indicates that specific podocyte
      proteins are closely related to podocyte function and biology. We hypothesized
      that podocyte failure, reflected by alteration of these proteins, leads not only
      to FSGS but also to resistance to steroid therapy. We investigated the
      association between expression of synaptopodin and glomerular epithelial protein
      1 (GLEPP1) and response to corticosteroid therapy in primary FSGS. The subjects
      of this retrospective study were 17 adult patients with primary FSGS with
      nephrotic syndrome (NS) seen at Fukuoka Red Cross Hospital between 1979 and 2001.
      They were divided into two groups according to the response to steroid therapy at
      6months: responders (n=10) and non-responders (persistence of nephrotic-range
      proteinuria, n=7). Expression levels of synaptopodin and GLEPP1 were examined
      immunohistochemically using image analysis software. Low expression levels of
      both proteins were associated with poor steroid responsiveness in FSGS. The
      average gray values for synaptopodin and GLEPP1 expression in responders vs. non
      responders were 9.0+/-0.7 (mean+/-S.E.M.) vs. 6.3+/-0.9 (P=0.04) and 9.6+/-1.2
      vs. 6.0+/-1.0 (P=0.04), respectively. The percentages of glomerular area staining
      for synaptopodin and GLEPP1 in responders vs. non-responders were 15.4+/-2.7% vs.
      8.1+/-1.2% (P=0.045) and 11.9+/-1.6% vs. 6.0+/-1.3% (P=0.02), respectively.
      Synaptopodin expression correlated with the severity of proteinuria and with
      GLEPP1 expression. Reduced expression of both synaptopodin and GLEPP1 is
      associated with poor response to steroid therapy in primary FSGS.

PMID- 16564555
TI  - Direct positive chronotropic action by angiotensin II in the isolated mouse
      atrium.
AB  - We observed the direct positive chronotropic effect of angiotensin II in mouse
      atria and characterized its pharmacological property. C57BL/6J mice were
      anesthetized with pentobarbital and hearts were quickly excised. Atrial
      preparations including right and left atrium were isolated and suspended in the
      organ bath filled with Krebs-Henseleit solution gassed with 95% O2 and 5% CO2.
      Angiotensin II at concentrations of 10(-10) to 10(-6) M caused concentration
      dependent increase in heart rate, and the maximal response was about 13% of that
      by isoproterenol. The effect was blocked by the selective AT1-receptor
      antagonist, losartan at concentrations of 10(-6) M, but not by the selective beta
      blocker, nadolol at concentration of 10(-5) M. Furthermore, angiotensin I also
      caused concentration-dependent increase in heart rate, and the effect was blocked
      by angiotensin converting enzyme (ACE) inhibitor, captopril at concentrations of
      10(-6) M. These results suggested that angiotensin I is converted to angiotensin
      II via ACE system in mice atria, and regulate heart rate through AT1-receptor
      stimulation, not by beta-adrenergic receptor.

PMID- 16564556
TI  - Polymorphisms in DNA repair genes as risk factors for asbestos-related malignant
      mesothelioma in a general population study.
AB  - Differences in response to carcinogenic agents are due to the allelic variants of
      the genes that control it. Key genes are those involved in the repair of the DNA
      damage caused by such agents. This paper describes the results of a case-control
      epidemiological study designed to determine the genotypes of four of these genes
      in persons exposed to a single genotoxic factor, i.e. asbestos, who had or had
      not developed malignant mesothelioma (MM). Our working hypothesis was that an
      imperfect DNA repair, as revealed by subtle polymorphic variants, could reduce
      protection against the chronic DNA insult provoked by asbestos and eventually
      result in mutagenesis and cancer. Seven variants (i.e. XRCC1-R399Q-NCBI SNP,
      XRCC1-R194W, XRCC3-T241M, XRCC3-IVS6-14, XPD-K751Q, XPD-D312N, OGG1-S326C) were
      investigated in 81 patients and 110 age and sex-matched controls, all residents
      at Casale Monferrato, a Piedmontese town highly exposed to asbestos pollution.
      Unconditional multivariable logistic regression was used to estimate odds ratios
      (ORs) and 95% confidence intervals (CIs). When considered as a categorical
      variable, XRCC1-399Q showed an increased OR both in heterozygotes (OR=2.08; 95%
      CI=1.00-4.33) and homozygotes (2.38; 95% CI=0.82-6.94), although individual ORs
      were not significant. When it was considered as a continuous variable OR was
      significant (OR=1.68; 95% CI: 1.02-2.75). When genotypes were divided into "non
      risk" and "risk" genotypes, i.e. those thought to be associated with increased
      risk in the light of the functional significance of the variants, XRCC1-399Q (Q
      homozygotes+Q/R heterozygotes versus R homozygotes) had an OR=2.147 (95% CI: 1.08
      4.28), whereas that of XRCC3-241T (T homozygotes+M/T heterozygotes versus M
      homozygotes) was 4.09 (95% CI: 1.26-13.21) and that of OGG1-326C was increased,
      though not significantly. None of the haplotypes showed a significantly different
      frequency between patients and controls. This is the first report of an
      association between polymorphisms in DNA repair genes and asbestos-associated MM.
      Our data indicate that genetic factors are involved in MM development.

PMID- 16564557
TI  - Oral physiology and mastication.
AB  - Mastication is a sensory-motor activity aimed at the preparation of food for
      swallowing. It is a complex process involving activities of the facial, the
      elevator and suprahyoidal muscles, and the tongue. These activities result in
      patterns of rhythmic mandibular movements, food manipulation and the crushing of
      food between the teeth. Saliva facilitates mastication, moistens the food
      particles, makes a bolus, and assists swallowing. The movement of the jaw, and
      thus the neuromuscular control of chewing, plays an important role in the
      comminution of the food. Characteristics of the food, e.g. water and fat
      percentage and hardness, are known to influence the masticatory process. Food
      hardness is sensed during mastication and affects masticatory force, jaw muscle
      activity, and mandibular jaw movements. When we chew for instance a crispy food,
      the jaw decelerates and accelerates as a result of resistance and breakage of
      food particles. The characteristic breakage behaviour of food is essential for
      the sensory sensation. This study presents a short review of the influence of
      oral physiology characteristics and food characteristics on the masticatory
      process.

PMID- 16564559
TI  - Bio-reduction of soluble chromate using a hydrogen-based membrane biofilm
      reactor.
AB  - Hexavalent chromium (Cr(VI)) is a mutagen and carcinogen that is a significant
      concern in water and wastewater. A simple and non-hazardous means to remove
      Cr(VI) is bioreduction to Cr(III), which should precipitate as Cr(OH)3(s). Since
      Cr(VI)-reducing bacteria can use hydrogen (H2) as an electron donor, we tested
      the potential of the H2-based membrane biofilm reactor (MBfR) for chromate
      reduction and removal from water and wastewater. When Cr(VI) was added to a
      denitrifying MBfR, Cr(VI) reduction was immediate and increased over 11 days.
      Short-term experiments investigated the effects of Cr(VI) loading, H2 pressure,
      and nitrate loading on Cr(VI) reduction. Increasing the H2 pressure improved
      Cr(VI) reduction. Cr(VI) reduction also was sensitive to pH, with an optimum near
      7.0, a sharp drop off below 7.0, and a gradual decline to 8.2. Cr(III)
      precipitated after a small upward adjustment of the pH. These experiments confirm
      that a denitrifying, H2-based MBfR can be used to reduce Cr(VI) to Cr(III) and
      remove Cr from water. The research shows that critical operational parameters
      include the H2 concentration, nitrate concentration, and pH.

PMID- 16564558
TI  - Macrophage activation and human immunodeficiency virus infection: HIV replication
      directs macrophages towards a pro-inflammatory phenotype while previous
      activation modulates macrophage susceptibility to infection and viral production.
AB  - Macrophages are pivotal for the regulation of immune and inflammatory responses,
      but whether their role in HIV infection is protective or deleterious remains
      unclear. In this study, we investigated the effect of pro- and anti-inflammatory
      stimuli on macrophage sensitivity to two different aspects of HIV infection:
      their susceptibility to infection stricto sensu, which we measured by endpoint
      titration method, and their ability to support virus spread, which we measured by
      using an RT activity assay in infection kinetics. We show a partially protective
      role for pro-inflammatory agents as well as for IL-4. We also illustrate that
      various different stimuli display differential effects on macrophage
      susceptibility to HIV and on virus replication that occurs thereafter. On the
      other hand, HIV replication strongly repressed CD206 and CD163 expression, thus
      clearly orientating macrophages towards a pro-inflammatory phenotype, but
      independently of TNF. Taken together, our results emphasize that HIV infection of
      macrophages sets up inflammation at the cell level but through unexpected
      mechanisms. This may limit target susceptibility and participate in virus
      clearance but may also result in tissue damage.

PMID- 16564560
TI  - Phosphorus removal by electric arc furnace steel slag and serpentinite.
AB  - Electric arc furnace (EAF) steel slag and serpentinite were tested in columns
      either alone or mixed with limestone to determine their capacity to remove
      phosphorus (P) from a solution containing initially 20mg P/L (for 114 days) than
      400mg P/L (for 21 days). EAF steel slag was nearly 100% efficient due to specific
      P adsorption onto metal hydroxides and precipitation of hydroxyapatite.
      Serpentinite also showed a good performance that decreased with time, adsorption
      appearing to be the dominant mechanism for P removal. Mixing limestone with these
      two materials did not improve their performance and in the case of serpentinite,
      it actually even decreased it. In 114 days of experimentation, serpentinite alone
      and the mixture of serpentinite and limestone removed 1.0mg P/g while in 180 days
      of experimentation, EAF steel slag and the mixture of slag and limestone removed
      an average of 2.2mg P/g, without attaining their maximum P removal potential. The
      void hydraulic retention time (HRTv) was a key factor for growing hydroxyapatite
      crystals and had a significant effect on P removal efficiency by EAF steel slag.
      A temporary increase in HRTv caused by clogging resulted in an increase in EAF
      steel slag efficiency (from 80% to almost 100%) towards the end of investigation.
      Results from this study indicate that the use of EAF steel slag in constructed
      wetlands or filter beds is a promising solution for P removal via adsorption and
      precipitation mechanisms.

PMID- 16564561
TI  - Occurrence and distribution of polybrominated diphenyl ethers (PBDEs) in the
      dissolved and suspended phases of the sea-surface microlayer and seawater in Hong
      Kong, China.
AB  - This study reports the first data on the concentration and distribution of
      polybrominated diphenyl ethers (PBDEs) in the sea-surface microlayer (SML), and
      their enrichment relative to bulk seawater, for coastal waters in the marine
      environment of Hong Kong, China. Samples were collected in March 2005 at five
      sample locations and analysed for eight congeners of primary interest, i.e. BDE
      28, 47, 99, 100, 153, 156, 183 and 209. Concentration ranges of summation
      operatorPBDE in the dissolved phase (DP, defined as sum of truly dissolved and
      colloidal phase) and suspended particulate matter (SPM) of seawater were 31.1
      118.7 pg/l (mean 70.7 pg/l), and 25.7-32.5 pg/l (mean 28.1 pg/l), respectively.
      Concentrations in the SML were generally higher by factor of 1.3-3.6 in the DP
      (concentration range from 40.2 to 228.2 pg/l, mean 149.2 pg/l) and by 0.3-2.1 in
      the SPM (concentration range 8.1-69.1 pg/l, mean 38.2 pg/l). Concentrations of
      PBDEs were general low and below detection limits in samples of an oceanic
      character and highest in the sheltered waters of Victoria Harbour. The congeners
      BDE 28, 47, 100 and 183 were most abundant, where BDE 209 was detected only in
      trace amounts. It is suggested that Hong Kong's marine waters show relatively low
      levels of PBDE contamination, and these compounds may originate from the disposal
      of electronic waste in southern China, as well as untreated discharge of
      wastewater locally.

PMID- 16564562
TI  - High surface area materials prepared from sewage sludge-based precursors.
AB  - This paper focuses on physical activation (CO2) and chemical activation (H3PO4,
      NaOH and KOH) of sewage sludge-based precursors. Our results show that (i) a
      simple acid washing treatment leads to a significant increase in the adsorption
      capacity of some precursors; (ii) under the experimental conditions tested, CO2
      physical activation and chemical activation with H3PO4 were ineffective for an
      efficient porosity development and (iii) choosing an appropriate protocol, it is
      possible to obtain highly porous materials (700-1700 m2 g(-1)) by chemical
      activation of sludge-based precursors with alkaline hydroxides. The efficiency of
      the chemical activation with NaOH or KOH is very much influenced by the method
      used for mixing the activating agent and the precursor. The BET values of the
      materials obtained when physically mixing ground hydroxides with the precursor
      almost doubled the values obtained if other mixing methods are employed.
      Increasing the hydroxide:precursor ratio leads to an enhancement of the
      adsorption capacity of the adsorbents, with BET values ranging from 689 to 1224
      m2 g(-1) for NaOH activation and from 853 to 1686 m2 g(-1) for KOH activation.

PMID- 16564563
TI  - Visual influences on primate encephalization.
AB  - Primates differ from most other mammals in having relatively large brains. As a
      result, numerous comparative studies have attempted to identify the selective
      variables influencing primate encephalization. However, none have examined the
      effect of the total amount of visual input on relative brain size. According to
      Jerison's principle of proper mass, functional areas of the brain devoted
      primarily to processing visual information should exhibit increases in size when
      the amount of visual input to those areas increases. As a result, the total
      amount of visual input to the brain could exert a large influence on
      encephalization because visual areas comprise a large proportion of total brain
      mass in primates. The goal of this analysis is to test the expectation of a
      direct relationship between visual input and encephalization using optic foramen
      size and optic nerve size as proxies for total visual input. Data were collected
      for a large comparative sample of primates and carnivorans, and three primary
      analyses were undertaken. First, the relationship between relative proxies for
      visual input and relative endocranial volume were examined using partial
      correlations and phylogenetic comparative methods. Second, to examine the
      generality of the results derived for extant primates, a parallel series of
      partial correlation and comparative analyses were undertaken using data for
      carnivorans. Third, data for various Eocene and Oligocene primates were compared
      with those for living primates in order to determine whether the fossil taxa
      demonstrate a similar relationship between relative brain size and visual input.
      All three analyses confirm the expectations of proper mass and favor the
      conclusion that the amount of visual input has been a major influence on the
      evolution of relative brain size in both primates and carnivorans. Furthermore,
      this study suggests that differences in visual input may partly explain (1) the
      high encephalization of primates relative to the primitive eutherian condition,
      (2) the high encephalization of extant anthropoids relative to other primates,
      and (3) the very low encephalization of Eocene adapiforms.

PMID- 16564564
TI  - Human growth hormone and interleukin-6 are upregulated in endometriosis and
      endometrioid adenocarcinoma.
AB  - In this retrospective and quantitated study on banked tissue we found that,
      compared to normal uterine epithelial cells, growth hormone (GH) is increased 3.4
      fold in endometriosis and 3.8-fold in endometrial adenocarcinoma. Similarly,
      interleukin-6 (IL-6) is increased 2.4-fold in endometriosis and 4.4-fold in
      endometrial adenocarcinoma. These proteins appear to be involved in the
      progression of both these conditions. GH is particularly interesting in this
      context since it is known to not only promote cellular proliferation but also
      reduces cell-cell adhesion, thus allowing individual cells to break away from
      their parent architecture. Our results suggest that both IL-6 and GH may play a
      role in the progression of both endometriosis and endometrial carcinoma.

PMID- 16564565
TI  - Ovarian carcinoma with thyroid metastases causing clinical hypothyroidism: a case
      report.
AB  - BACKGROUND: Ovarian cancer is known to metastasize to the thyroid gland. Despite
      an incidence of ovarian metastasis to the thyroid of 3-15%, clinical
      hypothyroidism resulting from such metastasis has not yet been reported. We
      present a case of metastatic ovarian cancer to the thyroid resulting in clinical
      hypothyroidism. CASE: A 55-year-old woman with recurrent papillary adenocarcinoma
      of the ovary presented with fatigue, abdominal distention, lymphedema, and
      depression. Thyroid stimulating hormone was markedly elevated, and thyroid biopsy
      demonstrated bilateral metastatic ovarian carcinoma. CONCLUSION: Although
      uncommon, metastatic disease to the thyroid should be considered when evaluating
      a patient with advanced ovarian cancer and clinical hypothyroidism.

PMID- 16564566
TI  - A proposed regional hierarchy in recovery of post-stroke aphasia.
AB  - Activation studies in patients with aphasia due to stroke or tumours in the
      dominant hemisphere have revealed effects of disinhibition in ipsilateral
      perilesional and in contralateral homotopic cortical regions, referred to as
      collateral and transcallosal disinhibition. These findings were supported by
      studies with selective disturbance of cortical areas by repetitive transcranial
      magnetic stimulation (rTMS) in healthy volunteers and in patients with focal
      brain lesions. Both, collateral as well as transcallosal disinhibition might be
      relevant for the compensation of lesions within a functional network. From these
      data a hierarchical organization of recovery of aphasia after stroke and of
      compensation of language defects due to brain tumours can be deduced, by which
      the reactivation of undamaged network areas of the ipsilateral hemisphere usually
      lead to better outcome than the involvement of homotopic contra-lateral regions.
      rTMS can be used to identify areas relevant for speech production and might play
      a role in treatment strategies targeted at modulating the activity of
      contralateral homotopic areas of the functional network which might interfere
      with language recovery.

PMID- 16564567
TI  - Fabrication and characterization of permeable degradable poly(DL-lactide-co
      glycolide) (PLGA) hollow fiber phase inversion membranes for use as nerve tract
      guidance channels.
AB  - Biodegradable permeable poly(DL-lactide-co-glycolide) (PLGA) hollow fiber
      membranes (HFMs) were fabricated using a wet phase inversion technique. By
      varying several parameters, such as the spinneret size, solvent and non-solvent
      pair, polymer concentration, flow rate, precipitation method, drop height, and
      small molecular pore-forming agents, PLGA HFMs with variable sizes, surface
      morphologies, porosities, and diffusive permeability were obtained. Under
      simulated physiological conditions in vitro, PLGA HFMs exhibited a degradation
      profile to accommodate nervous system regeneration and axonal outgrowth. While
      accelerated degradation resulted in substantial molecular weight loss starting at
      2 weeks and loss of selective permeability at 3 weeks, PLGA HFMs maintained gross
      structural integrity in the first 4 weeks, followed by sharp weight loss at 6
      weeks and complete disappearance at about 8 weeks. When compared to the raw PLGA
      material in a pellet form, which underwent heterogeneous degradation, the PLGA
      HFMs exhibited a homogeneous degradation where the surface and bulk degraded at
      approximately the same rate, and an overall lower degradation rate. Our results
      indicate that using a wet phase inversion technique, degradable HFMs with
      variable size, inner and outer surface morphologies, porosity, and permeability
      with potential applications for nerve tract guidance conduits can be fabricated.

PMID- 16564568
TI  - Repair of osteochondral defects with biphasic cartilage-calcium polyphosphate
      constructs in a sheep model.
AB  - There has been interest in developing novel biological treatments to repair focal
      cartilage defects. We have developed a method of forming biphasic constructs
      ("osteochondral"-type plug) in vitro consisting of cartilaginous tissue, formed
      on and anchored to the intended articulation surface of a porous ceramic
      substrate. The purpose of this study was to evaluate the biochemical and
      biomechanical properties and morphology of in vitro-formed biphasic constructs 3
      and 9 months after implantation into 4mm diameter full thickness osteochondral
      defects in the trochlear groove of sheep stifles. The implants withstood loading
      in vivo up to 9 months with evidence of fusion to adjacent native cartilage and
      fixation by bone ingrowth into the ceramic substrate. The cartilage layer was
      eroded from those implants that were proud to the joint surface. Control implants
      (ceramic only) had fibrous tissue on the articulating surface after implantation
      for 3-4 months. Neither the cellularity nor proteoglycan content of the implanted
      cartilage, when it remained, changed significantly between 3 and 9 months and the
      collagen content increased slightly. The elastic equilibrium modulus of the
      cartilage improved with time with the greatest improvement (10-fold) occurring
      early during the first 3-4 months after implantation. This study suggests that
      biphasic constructs may be suitable to repair joint defects as the implants were
      maintained up to 9 months in sheep. Importantly the mechanical properties of the
      implanted cartilage improved significantly after implantation suggesting that
      cartilage can mature in vivo after implantation. The results indicate that
      further study of this treatment approach is warranted to attempt to overcome the
      technical surgical difficulties identified in this study.

PMID- 16564570
TI  - Processing and mechanical properties of HA/UHMWPE nanocomposites.
AB  - A hydroxyapatite (HA) particulate reinforced ultrahigh molecular weight
      polyethylene (UHMWPE) nanocomposite was fabricated by compounding HA and UHMWPE
      mixtures in paraffin oil using twin-screw extrusion and then compression molding.
      Scanning electron microscope images revealed that HA aggregates were broken down
      to nano-sized particles and homogeneously dispersed in UHMWPE by the combined
      processes of twin-screw extrusion and UHMWPE swelling treatment. Transmission
      electron microscope images indicated the HA particles and UHMWPE matrix were
      intimately contacted through mechanical interlocking. The composite with the HA
      volume fraction of 0.23 exhibited a Young's modulus nine times higher than that
      of UHMWPE, while the composite maintained the excellent toughness feature of
      UHMWPE. The fracture strain reached over 300%, significantly higher than other
      types of biocomposites.

PMID- 16564569
TI  - Osteoblast functions on functionalized PMMA-based polymers exhibiting
      Staphylococcus aureus adhesion inhibition.
AB  - Staphylococcus aureus adhesion and osteoblast functions were assessed on
      functionalized poly(methyl methacrylate)-based terpolymers bearing randomly
      distributed carboxylate and sulfonate groups. These terpolymers were synthesized
      by radical polymerization, characterized by nuclear resonance spectroscopy and
      classified by the ratio R=[COO(-)/COO(-)+SO(3)(-)] in the range 0.5-0.8.
      Bacterial adhesion study showed that fibronectin-coated terpolymers with R
      varying from 0.5 to 0.8 exhibited inhibition rate of S. aureus adhesion from 90%
      to 98% as compared to the adhesion on unfunctionalized poly(methyl methacrylate).
      In contrast, the adhesion of osteoblasts onto the same functionalized terpolymers
      was decreased by 20% when compared to the results obtained on poly(methyl
      methacrylate). While the amount of attached osteoblasts are similar onto all the
      functionalized terpolymers whatever its R value, the cell proliferation was
      different and was found to vary with R in the range 0.5-0.8. Osteoblast
      proliferation, alkaline phosphatase activity and accumulation of calcium in the
      extracellular matrix of these cells, cultured on the functionalized terpolymers
      with R equal to 0.7-0.8 were similar to that observed onto non-functionalized
      poly(methyl methacrylate). In contrast, osteoblast proliferation was inhibited on
      terpolymers with an R value around 0.6. These results provide evidence that
      functionalized poly(methyl methacrylate)-based terpolymers with R ratio equaling
      0.7-0.8 simultaneously inhibit bacteria adhesion and support osteoblast functions
      pertinent to new bone formation. These functionalized polymers could, therefore,
      be used as coating or grafted on orthopedic and dental implants to render them
      both bone compatible and able to prevent bacterial infection.

PMID- 16564571
TI  - Bias-assisted in vitro calcification of calcium disilicide growth layers on spark
      processed silicon.
AB  - A dry-etch spark ablation method was used to produce calcium disilicide
      (CaSi2/Si) layers on silicon (Si) surfaces for the electrochemical growth of
      apatitic phosphates (calcium phosphate, CaP). CaSi2/Si composite electrodes
      readily calcify in vitro under the application of a small electric potential, and
      with proper treatment, the electrodeposition of CaP is localized to the sparked
      areas. In addition to increasing the local concentration of calcium, interfacial
      layers of CaSi2 on Si exhibit exceptional site selectivity towards CaP formation
      under bias due to the difference in conductivity between Si and CaSi2. The
      proposed mechanism for bias-assisted biomineralization of CaSi2/Si layers on
      spark-processed Si accounts for the physicochemical properties of deposited CaP
      films. This work also describes routes to surface modification of calcified
      composite electrodes with medicinally relevant compounds such as alendronate and
      norfloxacin. To assess the suitability of this material as a drug-delivery
      platform, release of the latter compound was also monitored as a function of
      time.

PMID- 16564572
TI  - Exploiting oxidative damage to overcome resistance.

PMID- 16564573
TI  - Prevalence of occult HBV infection among subjects with normal serum ALT levels in
      Korea.
AB  - OBJECTIVE: To investigate the prevalence of occult HBV infection among subjects
      with normal serum ALT levels in South Korea. METHODS: A total of 195 serum
      samples were collected from subjects without a past history of alcohol abuse and
      with normal serum ALT levels. They were negative for HBsAg, anti-HCV, and anti
      HIV. HBV-DNA was detected from sera by nested polymerase chain reaction (PCR)
      using specific primers of the surface antigen region of the HBV genome. We
      performed a quantitation assay using hybrid capture II test to determine the
      levels of serum HBV-DNA. RESULTS: HBV-DNA was detected in 31 of 195 subjects
      (16%). Prevalence of occult hepatitis B was significantly higher in the male
      subjects (23%) than in the female (8%), (P<0.05). We were able to detect HBV-DNA
      in 15% (7/47) even in which sera were all negative for anti-HBs and IgG anti-HBc.
      Serum HBV-DNA levels were as high as 10(5) copies/mL in 18 of 31 subjects (58%)
      with occult HBV infection. CONCLUSIONS: The prevalence of occult HBV infection
      and their HBV-DNA levels were significantly high among subjects with normal serum
      ALT levels in South Korea. Thus, more meticulous attention should be given to
      prevent HBV transmission by blood transfusion or organ transplantation in endemic
      areas, and further studies on clinical implication and mechanism of occult HBV
      infection are required.

PMID- 16564574
TI  - The use of radiotelemetry to evaluate electrographic seizures in rats with
      kainate-induced epilepsy.
AB  - Temporal lobe epilepsy in humans is a chronic condition with a highly variable
      temporal evolution. Animal models of this disorder have been developed to
      recapitulate many of the characteristics seen in humans with temporal lobe
      epilepsy. These animal models generate chronic spontaneous electrographic and
      motor seizures with a progressive increase in frequency over many months. In
      order to understand the underlying cellular and molecular mechanisms driving
      epileptogenesis, a practical means for accurately assessing seizure progression
      over this extended time period must be devised. In this report, we describe the
      use of a three-channel radiotelemetry system to record spontaneous electrographic
      interictal "spikes" and seizure activity from the cortical surface and the two
      hippocampi. This approach has allowed continuous recording before, during, and
      several months after kainate-induced status epilepticus. The important advantages
      of this approach are the potential for long-term continuous electrographic
      recording with comparatively unrestricted behavior; the disadvantages include
      increased cost, surgical difficulty and lower frequency-response in the
      recordings.

PMID- 16564575
TI  - Chicken cerebellar granule neurons rapidly develop excitotoxicity in culture.
AB  - Rat cerebellar granule cell culture is widely used as a model to study factors
      that control neuronal differentiation and death (e.g. excitotoxicity). However, a
      main drawback of this model is its dependence on depolarizing culture condition
      (25 mM potassium). In addition, it is quite expensive to maintain and requires
      animal facilities. Here we report that cerebellar granule neuron cultures from
      chicken may be used as an alternative model to study excitotoxicity.
      Surprisingly, fetal chicken cells may be grown in a physiological potassium
      concentration (5 mM potassium). They develop excitotoxicity rapidly in culture
      (fully developed at 3 days in vitro), and respond to glutamate excitotoxicity
      similar to rat cultures (ROS production and activation of caspase-3).

PMID- 16564576
TI  - Transforming growth factor beta 1(TGF-beta1) down-regulates TNFalpha-induced
      RANTES production in rheumatoid synovial fibroblasts through NF-kappaB-mediated
      transcriptional repression.
AB  - Transforming growth factor (TGF)-beta1 is a pleiotropic cytokine with many
      functions, including those related to growth modulation, immunosuppression, and
      pro-inflammation, in a wide variety of cell types. In this study, we investigated
      the ability of TGF-beta1 to regulate RANTES production by activated rheumatoid
      synovial fibroblasts. Fibroblast-like synoviocytes (FLS) were cultured in the
      presence of TGF-beta1 and IL-1beta, IL-15, TNFalpha, or IL-17, and the secretion
      of RANTES into culture supernatants was measured by enzyme-linked immunosorbent
      assay (ELISA). Expression of RANTES encoded mRNA was determined by reverse
      transcription-polymerase chain reaction (RT-PCR), and NF-kappaB binding activity
      for RANTES transcription was determined by electrophoretic mobility shift assay
      (EMSA). We found that the concentrations of RANTES in synovial fluid (SF) from
      rheumatoid arthritis (RA) patients were lower than in SF from osteoarthritis (OA)
      patients, whereas the concentrations of TGF-beta1 were higher in RA SF than in OA
      SF. TGF-beta1 dose-dependently inhibited TNFalpha-induced production of RANTES
      protein and mRNA from RA FLS. Addition of RA SF with high-level TGF-beta1
      mimicked the effect of TGF-beta1 on TNFalpha-induced RANTES production, which was
      inhibited by treatment with anti-TGF-beta1 neutralizing antibody. TGF-beta1
      blocked the degradation of cytosolic IkappaB-alpha and the translocation of
      activated NF-kappaB to the nucleus. EMSA showed that the inhibitory effect of TGF
      beta1 was associated with decreased binding of NF-kappaB to the RANTES promoter.
      These results suggest that elevated TGF-beta1 in rheumatoid synovial tissue may
      suppress joint inflammation by inhibiting RANTES secretion from synovial
      fibroblasts, thus blocking the infiltration of immune cells. These findings may
      provide an explanation for the mechanism by which TGF-beta1 regulates immune
      function in RA.

PMID- 16564577
TI  - T cell gene expression profiling identifies distinct subgroups of Japanese
      multiple sclerosis patients.
AB  - To clarify the molecular background underlying the heterogeneity of multiple
      sclerosis (MS), we characterized the gene expression profile of peripheral blood
      CD3+ T cells isolated from MS and healthy control (CN) subjects by using a cDNA
      microarray. Among 1258 cDNAs on the array, 286 genes were expressed
      differentially between 72 untreated Japanese MS patients and 22 age- and sex
      matched CN subjects. When this set was used as a discriminator for hierarchical
      clustering analysis, it identified four distinct subgroups of MS patients and
      five gene clusters differentially expressed among the subgroups. One of these
      gene clusters was overexpressed in MS versus CN, and particularly enhanced in the
      clinically most active subgroup of MS. After 46 of the MS patients were treated
      with interferon-beta (IFNbeta-1b) for two years, IFNbeta responders were
      clustered in two of the four MS subgroups. Furthermore, the IFNbeta responders
      differed from nonresponders in the kinetics of IFN-responsive genes at 3 and 6
      months after starting IFNbeta treatment. These results suggest that T-cell gene
      expression profiling is valuable to identify distinct subgroups of MS associated
      with differential disease activity and therapeutic response to IFNbeta.

PMID- 16564578
TI  - Viral upper respiratory tract infections in young children with emphasis on acute
      otitis media.
AB  - Viral upper respiratory infection is the most common reason for seeking medical
      care for children. Recurrent viral respiratory infections and subsequent
      complications (e.g. acute otitis media (AOM)) are a burden for children, their
      families and society. Over the past decade, our knowledge on the significance of
      respiratory viruses has broadened remarkably. Viruses cause large variety of
      respiratory diseases and cause alone diseases, which previously have been assumed
      to be bacterial only (e.g. AOM and pneumonia). Methods for detection analysis of
      respiratory viruses are developing making both the diagnosis and epidemiological
      investigations of respiratory infections easier. Accurate diagnosis of
      respiratory infections and awareness of possible viral etiology could reduce the
      use of antibiotics. Etiologic studies of viral infections are becoming
      increasingly important, with the emergence of new antiviral drugs and vaccines.

PMID- 16564579
TI  - A statistical method for comparing viral growth curves.
AB  - Viral replication is often analyzed by growth curves, in which viral
      multiplication in the presence of host cells is measured as a function of time.
      Comparing growth curves is one of the most sensitive ways of comparing viral
      growth under different conditions or for comparing replication of different viral
      mutants. However, such experiments are rarely analyzed in a statistically
      rigorous fashion. Here a statistical method is described for comparing curves,
      using replication of HIV in the presence of an integrase inhibitor as an example.
      A complication in the analysis arises due to the fact that sequential
      measurements of virus accumulation are not independent, which constrains the
      choice of statistical method. In the recommended approach, the values for virus
      accumulation over time are fitted to an exponential equation, then the means of
      the extracted growth rates compared using a nonparametric test, either the Mann
      Whitney U-test for two samples or the Kruskal-Wallis test for multiple samples. A
      web-based tutorial for implementing this method is available at
      http://microb230.med.upenn.edu/tutorials/wangTutorial.

PMID- 16564580
TI  - Emerging challenges of assigning P2X7 receptor function and immunoreactivity in
      neurons.
AB  - Currently available antibodies to the P2X(7) receptor are unreliable determinants
      of neuronal P2X(7) immunoreactivity, owing to staining of a "P2X(7)-like" protein
      that is not eliminated by legitimate P2X(7) gene-knockout approaches. Despite
      this, compelling electrophysiological and pharmacological data strongly support a
      role for P2X(7) receptors in neuronal function and injury. A major priority for
      the field now is to identify the neuronal "P2X(7)-like" protein and develop
      effective antibodies selective for neuronal P2X(7) immunoreactivity. Until this
      occurs, we are dependent on rigorous application of multiple pharmacological
      criteria for attribution of neuronal function to P2X(7) receptors in non-human
      tissues, including greater activity in response to BzATP than to ATP, sensitivity
      to blockade by nanomolar concentrations of Brilliant Blue-G, irreversible
      antagonism by periodate-oxidized ATP, and lack of inhibition by suramin.

PMID- 16564581
TI  - Effects of Cu on plasma cortisol and cortisol secretion by adrenocortical cells
      of rainbow trout (Oncorhynchus mykiss).
AB  - Fish are exposed to multiple stressors, often acting concurrently, in their
      environment. To evaluate the potential of Cu to act as a chemical stressor,
      rainbow trout (Oncorhynchus mykiss) were exposed to Cu (30 or 80 microg/l) for 30
      days in the laboratory and they were subjected to a physical stressor (1 min air
      exposure) before sampling. Physiological stress indicators in the whole fish as
      well as cortisol secretion by adrenocortical cells in vitro were measured. Fish
      exposed to Cu had a lower condition factor, hepatosomatic index, plasma glucose,
      hepatic glycogen and gill Na(+)/K(+)-ATPase activity compared to controls.
      Exposure to Cu did not have an effect on basal plasma cortisol (fish sampled
      without air exposure stress) however, the air exposure-induced increase in plasma
      cortisol was lower in fish exposed to Cu. Cortisol secretion stimulated by ACTH
      in vitro was greater in adrenocortical cells isolated from fish exposed to Cu in
      vivo but in vitro exposure to Cu consistently impaired cortisol secretion. Our
      results indicate that Cu at high concentrations disrupts cortisol secretion
      through a direct toxic effect on adrenocortical cells while low concentrations
      resulting from a 30-day exposure to environmentally relevant Cu concentrations
      enhances cortisol secretion in response to ACTH in vitro.

PMID- 16564582
TI  - Biomphalaria glabrata cytosolic copper/zinc superoxide dismutase (SOD1) gene:
      association of SOD1 alleles with resistance/susceptibility to Schistosoma
      mansoni.
AB  - Variation in susceptibility of the snail Biomphalaria glabrata to infection by
      the parasite Schistosoma mansoni is, at least in part, genetically determined.
      Functional studies have demonstrated that hemocyte-mediated killing of the
      parasite involves hydrogen peroxide, the enzymatic product of superoxide
      dismutase (SOD). The present study identifies alleles of the gene coding for
      cytosolic copper/zinc SOD (SOD1). The resistance/susceptibility phenotypes and
      SOD1 genotypes were determined for 354 snails of the predominantly resistant 13
      16-R1 strain of B. glabrata. Resistance to the parasite was found to be
      significantly associated with one allele of the SOD1 gene. Conversely, a separate
      SOD1 allele was significantly associated with susceptibility.

PMID- 16564583
TI  - Regulation of surface coat exchange by differentiating African trypanosomes.
AB  - African trypanosomes (Trypanosoma brucei) have a digenetic lifecycle that
      alternates between the mammalian bloodstream and the tsetse fly vector. In the
      bloodstream, replicating long slender parasites transform into non-dividing short
      stumpy forms. Upon transmission into the fly midgut, short stumpy cells
      differentiate into actively dividing procyclics. A hallmark of this process is
      the replacement of the bloodstream-stage surface coat composed of variant surface
      glycoprotein (VSG) with a new coat composed of procyclin. Pre-existing VSG is
      shed by a zinc metalloprotease activity (MSP-B) and glycosylphosphatidylinositol
      specific phospholipase C (GPI-PLC). We now provide a detailed analysis of the
      coordinate and inverse regulation of these activities during synchronous
      differentiation. MSP-B mRNA and protein levels are upregulated during
      differentiation at the same time as proteolysis whereas GPI-PLC levels decrease.
      When transcription or translation is inhibited, VSG release is incomplete and a
      substantial amount of protein stays cell-associated. Both modes of release are
      still evident under these conditions, but GPI hydrolysis plays a quantitatively
      minor role during normal differentiation. Nevertheless, GPI biosynthesis shifts
      early in differentiation from a GPI-PLC sensitive structure to a resistant
      procyclic-type anchor. Translation inhibition also results in a marked increase
      in the mRNA levels of both MSP-B and GPI-PLC, consistent with negative regulation
      by labile protein factors. The relegation of short stumpy surface GPI-PLC to a
      secondary role in differentiation suggests that it may play a more important role
      as a virulence factor within the mammalian host.

PMID- 16564584
TI  - A novel strategy to extract specific phylogenetic sequence information from
      community T-RFLP.
AB  - Cultivation-independent analyses of soil microbial community structures are
      frequently used to describe microbiological soil characteristics. Semi-automated
      terminal restriction fragment length polymorphism (T-RFLP) analyses yield high
      resolution genetic profiles of highly diverse soil microbial communities and hold
      great potential for use in routine soil quality monitoring. A serious limitation
      of T-RFLP analyses has been the inability to reliably affiliate observed terminal
      restriction fragments (T-RF) to phylogenetic groups. In the study presented here,
      we were able to overcome this limitation of T-RFLP. With a combination of adapter
      ligation, fragment size selection, and re-amplification with adapter site
      specific PCR, we were able to isolate a T-RF-fraction of a narrow size-range
      containing a T-RF that was significantly more abundant in heavy metal amended
      soils. Cloning the size-selected T-RF fraction allowed for the efficient
      isolation of clones containing this specific T-RF. Sequence determination and
      phylogenetic inference in RDP-II affiliated the sequence to unclassified
      cyanobacteria. Specific primer design and PCR amplification from bulk soil DNA
      allowed for independent confirmation of the results from bacterial T-RFLP and T
      RF cloning. Our results show that specific T-RFs can be efficiently isolated and
      identified, and that the adapter ligation approach holds great potential for
      genetic profiling and for identification of community components of interest.

PMID- 16564585
TI  - Real-time PCR for the detection of Salmonella spp. in food: An alternative
      approach to a conventional PCR system suggested by the FOOD-PCR project.
AB  - A real-time PCR assay using non-patented primers and a TaqMan probe for the
      detection and quantification of Salmonella spp. is presented. The assay is based
      on an internationally validated conventional PCR system, which was suggested as a
      standard method for the detection of Salmonella spp. in the FOOD-PCR project. The
      assay was sensitive and specific. Consistent detection of 9.5 genome equivalents
      per PCR reaction was achieved, whereas samples containing an average of 0.95
      genome equivalents per reaction were inconsistently positive. The assay performed
      equally well as a commercially available real-time PCR assay and allowed
      sensitive detection of Salmonella spp. in artificially contaminated food. After
      enrichment for 16 h in buffered peptone water (BPW) or universal pre-enrichment
      broth (UPB) 2.5 CFU/25 g salmon and minced meat, and 5 CFU/25 g chicken meat and
      25 ml raw milk were detected. Enrichment in BPW yielded higher numbers of CFU/ml
      than UPB for all matrices tested. However, the productivity of UPB was
      sufficient, as all samples were positive with both real-time PCR methods,
      including those containing less than 300 CFU/ml enrichment broth (enrichment of 5
      CFU/25 ml raw milk in UPB).

PMID- 16564586
TI  - Autoinducer-2 bioassay is a qualitative, not quantitative method influenced by
      glucose.
AB  - Autoinducer-2 (AI-2) is a cell-to-cell signaling molecule which is thought to be
      utilized for quorum sensing processes by a variety of prokaryotic species. This
      molecule is usually detected using a so-called autoinducer bioassay, which relies
      on the ability of a Vibrio harveyi reporter strain to produce light in response
      to AI-2. However, as previously reported, the presence of glucose in the sample
      can inhibit the bioluminescence of the reporter strain, a fact that is often
      ignored by investigators. Our data suggest that the presence of glucose in
      concentrations below that required for the inhibition of bioluminescence may lead
      to incorrect AI-2 readings and produce misleading (false-positive) results. Our
      findings also suggest that even if all the limitations of this bioassay are
      considered, the large standard deviation of the method allows only for a
      qualitative and not quantitative interpretation of the obtained results.

PMID- 16564587
TI  - Biotechnology offers revolution to fish health management.
AB  - Biotechnology has many applications in fish health management. The application of
      monoclonal antibodies (mAbs) provides a rapid means of pathogen identification;
      antibodies to immunoglobulins from different fish species can be used to monitor
      the host response following vaccination; and mAbs also have the potential for
      screening broodstock for previous exposure to pathogens. Luminex technology
      exemplifies a novel antibody-based method that can be applied to both pathogen
      detection and vaccine development. Molecular technologies, such as the polymerase
      chain reaction (PCR), real time PCR and nucleic acid sequence-based amplification
      (NASBA), have enabled detection, identification and quantification of extremely
      low levels of aquatic pathogens, and microarray technologies offer a new
      dimension to multiplex screening for pathogens and host response. Recombinant DNA
      technology permits large-scale, low-cost vaccine production, moreover DNA
      vaccination, proteomics, adjuvant design and oral vaccine delivery will
      undoubtedly foster the development of effective fish vaccines in the future.

PMID- 16564588
TI  - [18F]fluoro-deoxy-glucose positron emission tomography ([18F]FDG-PET) voxel
      intensity-based intensity-modulated radiation therapy (IMRT) for head and neck
      cancer.
AB  - BACKGROUND AND PURPOSE: Focused dose escalation may improve local control in head
      and neck cancer. Planning results of [(18)F]fluoro-deoxy-glucose positron
      emission tomography ([(18)F]FDG-PET) voxel intensity-based intensity-modulated
      radiation therapy (IMRT) were compared with those of PET contour-based IMRT.
      PATIENTS AND METHODS: PET contour-based IMRT aims to deliver a homogeneous boost
      dose to a PET-based subvolume of the planning target volume (PTV), called
      PTV(PET). The present PET voxel intensity-based planning study aims to prescribe
      the boost dose directly as a function of PET voxel intensity values, while
      leaving the dose distribution outside the PTV unchanged. Two escalation steps
      (2.5 and 3 Gy/fraction) were performed for 15 patients. RESULTS: PTV(PET) was
      irradiated with a homogeneous dose in the contour-based approach. In the voxel
      intensity-based approach, one or more sharp dose peaks were created inside the
      PTV, following the distribution of PET voxel intensity values. CONCLUSIONS: While
      PET voxel intensity-based IMRT had a large effect on the dose distribution within
      the PTV, only small effects were observed on the dose distribution outside this
      PTV and on the dose delivered to the organs at risk. Therefore both methods are
      alternatives for boosting subvolumes inside a selected PTV.

PMID- 16564589
TI  - Sparing of the submandibular glands by intensity modulated radiotherapy in the
      treatment of head and neck cancer.
AB  - BACKGROUND AND PURPOSE: The submandibular glands produce most of the unstimulated
      saliva output and are the key in prevention of radiation-related xerostomia. We
      investigated whether sparing of the submandibular function is feasible with
      intensity modulated radiotherapy (IMRT). PATIENTS AND METHODS: Thirty-six
      patients diagnosed with head and neck cancer were treated with IMRT and had at
      least one parotid gland excluded from the planning target volume. In a subset, of
      these patients (n=18) where the risk of cancer recurrence in the contralateral
      submandibular region was judged low, the contralateral submandibular gland was
      spared from full-dose irradiation. The total unstimulated and stimulated salivary
      flow rates and adverse effects were monitored. RESULTS: Twelve months following
      IMRT mean unstimulated saliva flow was 60% of the baseline value among patients
      who had one submandibular gland spared and 25% among those who did not (P=0.006).
      Patients whose contralateral submandibular was spared reported less grade two or
      three xerostomia (4 vs. 11; P=0.018), and used less saliva substitutes. No cancer
      recurrences were detected at the vicinity of the spared glands during a median
      follow-up time of 31 months. CONCLUSIONS: Submandibular gland sparing with IMRT
      is safe in selected patients treated for head and neck cancer. It is effective in
      prevention of radiation-associated xerostomia.

PMID- 16564590
TI  - Preoperative hyper-fractionated accelerated radiotherapy (HART) in locally
      advanced rectal cancer (LARC) immediately followed by surgery. A prospective
      phase II trial.
AB  - BACKGROUND AND PURPOSE: We aim to report on local control in a phase II trial on
      preoperative hyper-fractionated and accelerated radiotherapy schedule (HART) in
      locally advanced resectable rectal cancer (LARC). This fractionation schedule was
      designed to keep the overall treatment time (OTT) as short as possible. PATIENTS
      AND METHODS: This is a prospective trial on patients with UICC stages II and III
      rectal cancer. The patients were submitted to a total dose of 41.6 Gy, delivered
      in 2.5 weeks at 1.6 Gy per fraction twice a day with a 6-h interfraction
      interval. Surgery was performed within 1 week after the end of irradiation.
      Adjuvant chemotherapy was delivered in a subset of patients. RESULTS: Two hundred
      and seventy nine patients were entered and 250 are fully assessable, with a
      median follow-up of 39 months. The 5-years actuarial local control (LC) rate is
      91.7%. The overall survival (OS) is 59.6%. The freedom from disease relapse (FDR)
      is 71.5%. Downstaging was observed in 38% of the tumors. CONCLUSION: The
      actuarial LC at 5 years is 91.7%, although we are dealing with stages II-III
      LARC, mainly located in the lower rectum (median distance = 5 cm). The pattern of
      failure is dominated by distant metastases and treatment intensification will
      obviously require a systemic approach.

PMID- 16564591
TI  - Comparison of forward planning with automated inverse planning for three
      dimensional conformal radiotherapy of non-small cell lung cancer without IMRT.
AB  - The forward and inverse treatment plans of 10 patients with lung cancer were
      compared in terms of PTV coverage, sparing of normal lung and time required to
      generate a plan. The inverse planning produced as good treatment plans as an
      experienced dosimetrist with considerable reduction in staff time. When
      translated to other complex sites, inverse non-IMRT planning may have
      considerable impact on manpower requirements.

PMID- 16564592
TI  - Changes in the respiratory pattern during radiotherapy for cancer in the lung.
AB  - BACKGROUND AND PURPOSE: To quantify changes in patients' diaphragm motion pattern
      over the course of radiotherapy and to evaluate the implications of these changes
      for 4D radiotherapy. PATIENTS AND METHODS: From January 2004 to October 2004, 10
      patients with lung malignancies treated at our department underwent weekly
      respiratory motion verification during the course of external beam radiation. An
      onboard kilovoltage imaging system was used to acquire fluoroscopy weekly for
      patients with lung neoplasms. The diaphragm position as a function of time was
      extracted automatically from the fluoroscopy and used to calculate the daily mean
      and daily SD of motion. The diaphragm position was related to both a bony
      reference point and machine isocenter. Changes in the daily mean and daily SD in
      relation to the reference (first day) daily mean and reference daily SD were
      measured. RESULTS: The mean change in the daily mean was 0.32 mm+/-6.11 mm in
      relation to the bony reference point and 0.38 mm+/-6.28 mm in relation to
      isocenter. The mean change in the daily SD was 0.91 mm+/-1.81 mm. The mean
      systematic change in the daily mean was 4.97 mm, and the mean random change in
      the daily mean was 3.61 mm. CONCLUSIONS: Daily verification of 4D radiotherapy
      techniques to assess the necessity of online set-up correction may be required
      due to the large change in the mean diaphragm position observed for these
      patients. However, the variation of the daily SD was small for most patients.
      Adaptive adjustment of the margin may be necessary for those patients with larger
      variation of the daily SD.

PMID- 16564593
TI  - Radiation exposure after permanent prostate brachytherapy.
AB  - BACKGROUND AND PURPOSE: Limited information is available on the true radiation
      exposure and associated risks for the relatives of the patients submitted to
      prostate brachytherapy with permanent implant of radioactive sources and for any
      other people coming into contact with them. In order to provide appropriate
      information, we analyzed the radiation exposure data from 216 prostate cancer
      patients who underwent (125)I or (103)Pd implants at the European Institute of
      Oncology of Milan, Italy. PATIENTS AND METHODS: Between October 1999 and October
      2004, 216 patients with low risk prostate carcinoma were treated with (125)I (200
      patients) or (103)Pd (16 patients) permanent seed implantation. One day after the
      procedure, radiation exposure measurements around the patients were performed
      using an ionization chamber survey meter (Victoreen RPO-50) calibrated in dose
      rate at an accredited calibration center (calibration Centre SIT 104). RESULTS:
      The mean dose rate at the posterior skin surface (gluteal region) following
      (125)I implants was 41.3 microSv/h (range: 6.2-99.4 microSv/h) and following
      (103)Pd implants was 18.9 microSv/h (range 5.0-37.3 microSv/h). The dose rate at
      50 cm from the skin decreased to the mean value of 6.4 microSv/h for the (125)I
      implants and to the mean value of 1.7 microSv/h for the (103)Pd implants. Total
      times required to reach the annual dose limit (1 mSv/year) recommended for the
      general population by the European Directive 96/29/Euratom and by the Italian law
      (Decreto Legislativo 241/2000) at a distance of 50 cm from the posterior skin
      surface of the implanted patient would be 7.7 and 21.6 days for (125)I and for
      (103)Pd. Good correlation between the measured dose rates and both the total
      implanted activity and the distance between the most posteriorly implanted seed
      and the skin surface of the patients was found. CONCLUSIONS: Our data show that
      the dose rates at 50 cm away from the prostate brachytherapy patients are very
      low and that the doses possibly absorbed by the relatives and other members of
      the general population coming into contact with the treated patients are well
      below the dose limit set by the European Directive and by the Italian regulation.
      However, in order to meet the recommendation of the ALARA principle (As Low As
      Reasonably/Readily Achievable), some advice to the patients should be given, such
      as to maintain a minimum distance from the patient of 1m, at least for a period
      equal to one half life of used radionuclide (60 days for (125)I and 15 days for
      (103)Pd).

PMID- 16564594
TI  - Analysis of interfractional set-up errors and intrafractional organ motions
      during IMRT for head and neck tumors to define an appropriate planning target
      volume (PTV)- and planning organs at risk volume (PRV)-margins.
AB  - BACKGROUND AND PURPOSE: To analyze the interfractional set-up errors and
      intrafractional organ motions and to define appropriate planning target volume
      (PTV)- and planning organs at risk volume (PRV)-margins in intensity-modulated
      radiotherapy (IMRT) for head and neck tumors. PATIENTS AND METHODS: Twenty-two
      patients with head and neck or brain tumors who were treated with IMRT were
      enrolled. The set-up errors were defined as the displacements of the coordinates
      of bony landmarks on the beam films from those on the simulation films. The organ
      motions were determined as the displacements of the coordinates of the landmarks
      on the images recorded every 3 min for 15 min on the X-ray simulator from those
      on the initial image. RESULTS: The standard deviations (SDs) of the systematic
      set-up errors (Sigma-INTER) and organ motions (Sigma-intra) distributed with a
      range of 0.7-1.3 and 0.2-0.8 mm, respectively. The average of the SDs of the
      random set-up errors (sigma-INTER) and organ motions (sigma-intra) ranged from
      0.7 to 1.6 mm and from 0.3 to 0.6 mm, respectively. Appropriate PTV-margins and
      PRV-margins for all the landmarks ranged from 2.0 to 3.6 mm and from 1.8 to 2.4
      mm, respectively. CONCLUSIONS: We have adopted a PTV-margin of 5mm and a PRV
      margin of 3mm for head and neck IMRT at our department.

PMID- 16564595
TI  - Contribution of a selected fungal population to the volatile compounds on dry
      cured ham.
AB  - Dry-cured ham is obtained after several months of ripening. Different fungi
      strive on the surface, including toxigenic molds. Proteolysis and lipolysis by
      the endogenous and microbial enzymes seem to play a decisive role in the
      generation of flavor precursors in dry-cured meat products. In addition, fungi
      show a positive impact on the volatile compounds of ripened pork loins. However,
      the contribution of the fungal population to flavor formation in dry-cured ham
      remains unclear. One selected strain each of Penicillium chrysogenum and
      Debaryomyces hansenii was inoculated as starter cultures on dry-cured ham.
      Volatile compounds extracted by solid phase micro-extraction technique were
      analyzed by gas chromatography/mass spectrometry. A trained panel evaluated
      flavor and texture of fully ripened hams. The wild fungal population on non
      inoculated control hams correlates with higher levels of short chain aliphatic
      carboxylic acids and their esters, branched carbonyls, branched alcohols, and
      some sulfur compounds, particularly at the outer muscle. Conversely, P.
      chrysogenum and D. hansenii seem to be responsible for higher levels of long
      chain aliphatic and branched hydrocarbons, furanones, long chain carboxylic acids
      and their esters. The very limited impact of P. chrysogenum on pyrazines in
      inoculated hams can be due to the activity of the yeast. Lower levels for some of
      the more volatile linear carbonyls at the ham surface suggest an anti-oxidant
      effect by micro-organisms. The differences in volatile compounds did not show a
      neat impact on flavor in the sensorial analysis. Nonetheless, inoculated hams got
      a better overall acceptability, which has to be attributed to their improved
      texture. The lower toughness of inoculated hams is a direct consequence of an
      early settling of a highly proteolytic mold. Thus, the use of selected fungi as
      starter cultures may be useful to obtain high-quality and safe dry-cured ham.

PMID- 16564596
TI  - Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139)
      via transferrin receptor-targeted liposomes.
AB  - A novel transferrin receptor (TfR)-targeted liposomal formulation was synthesized
      and evaluated for the delivery of a phosphorothioate antisense
      oligodeoxyribonucleotide (ODN) (G3139, oblimerson sodium, or Genasense) to Bcl-2
      in K562 leukemia cells. Liposomes composed of DC-Chol/egg PC/PEG-DSPE
      (25:73.5:1.5, mol/mol/mol) were loaded with G3139 with high efficiency (70-80%).
      To prepare targeted liposomes, transferrin was first coupled to PEG-DSPE and then
      incorporated into the bilayer by post-insertion. The liposomes had a mean
      diameter of 100 to 150 nm and exhibited colloidal stability for up to 8 weeks.
      Uptake of Tf-conjugated G3139-containing liposomes in TfR positive K562 cells was
      found to be more efficient than that of the non-targeted control formulation and
      could be blocked by excess free Tf. Treatment with Tf-conjugated liposomes
      resulted in Bcl-2 protein downregulation in K562 cells that was approximately 2
      fold greater than with non-targeted liposomes (p<0.05) and 10-fold greater than
      with free G3139. Treatment with 2 microM G3139 in Tf-conjugated liposomes
      resulted in >80% reduction in Bcl-2 transcript. In addition, Tf-conjugated
      liposomal G3139-sensitized K562 cells to daunorubicin, lowering IC50 from 1.8
      microM to 0.18 microM. In conclusion, Tf-conjugated liposomes are effective
      delivery vehicles for G3139 antisense oligos in TfR positive K562 cells and
      warrant further investigation as an in vivo oligo delivery vehicle.

PMID- 16564597
TI  - Electrochemical Time-of-Flight in crosslinked collagen matrix solution:
      implications of structural changes for drug delivery systems.
AB  - Electrochemical Time-of-Flight (ETOF) method was used for the first time to
      measure the diffusion coefficient of 4-hydroxy-TEMPO, a molecular probe in
      collagen I matrix solution as a function of its concentration and the extent of
      crosslinking with glutaraldehyde (GA). The values of the diffusion coefficient
      were correlated with Circular Dichroism (CD) and viscosity data to assess the
      changes of the structure of a collagen matrix. The low value of probe diffusion
      coefficient indicates that the molecular collagen contributes to large diffusion
      hindrance of the medium. The combined Brinkman or effective medium model and the
      Carman-Kozeny model were used to estimate the average diameter of a matrix pore
      as a function of collagen solution composition. We show that 0.5% and 1% (w/w)
      collagen matrix crosslinked with the addition of GA above 0.1% (v/w) forms matrix
      with pores larger than in native collagen. This result suggests the existence of
      a micro-phase separation in the crosslinked collagen matrix. The implications of
      these findings for the design of small molecule drug delivery systems are
      discussed.

PMID- 16564599
TI  - A simplified protocol to screen for distal polyneuropathy in type 2 diabetic
      patients.
AB  - To test a simplified protocol to screen type 2 diabetic patients (DM2) for distal
      polyneuropathy (DPN), 80 outpatients and 45 controls answered a symptom
      questionnaire, underwent a directed examination (pin-prick, tuning fork,
      monofilament, ankle jerk, cold spatula and walking on heels), autonomic tests,
      and an electroneurophysiological study (EMG). Symptoms were also analysed as
      scores. DPN was diagnosed in the presence of abnormal EMG (or autonomic
      neuropathy), plus one symptom or one abnormal objective finding. Symptoms were
      equally frequent in patients (56%) and controls (35%, P=0.20). Objective findings
      were more frequent in patients (62/80 versus 11/45; P<0.05). The 60 DM2 patients
      with DPN were older, with longer diabetes duration and more often hypertensive
      than those without DPN. The 15 patients unable to walk on heels had DPN
      (sensitivity 20.8%, specificity 100%, positive predictive value 100% and negative
      predictive value 12.3%). The 12 patients able to walk on heels but with three or
      more abnormal tests had DPN (sensitivity 21.1%, specificity 100%, positive
      predictive value 100% and negative predictive value 15.1%). Isolated signs and
      symptoms do not identify patients with DPN. Patients with higher degrees of
      impairment can be identified by six simple ambulatory tests, reducing in one
      third the need for EMG.

PMID- 16564598
TI  - The Gly146Ala variation in human SF-1 gene: its association with insulin
      resistance and type 2 diabetes in Chinese.
AB  - AIMS: While steroidogenic factor 1 (SF-1) is traditionally an essential nuclear
      receptor for steroidogenic tissues, current emerging studies revealed that the
      receptor is also closely implicated in metabolism. Mutations of SF-1 gene cause
      metabolic disorders like obesity in both human and mice. The aim of the present
      study is to examine whether the Gly146Ala variation in the gene for SF-1, that is
      known to impair SF-1 function and related to adrenal disorders, affects
      susceptibility to type 2 diabetes. METHODS: Hundred and fifty-one type 2 diabetic
      subjects and 141 non-diabetic control subjects of Han Chinese were recruited and
      the SF-1 genotype were analyzed by PCR-RFLP method. RESULTS: The Gly146Ala
      variation occurs frequently in the Han Chinese. Allele Ala frequency in the
      control subjects (27.3%) was significantly lower than that in type 2 diabetic
      subjects (37.1%, chi2=6.37, p=0.01). The Gly/Ala and Ala/Ala genotypes
      frequencies were also higher in diabetic subjects. In both the diabetic and
      control populations, subjects carrying allele Ala, as compared to those not, had
      higher fasting insulin levels and higher HOMA values. CONCLUSIONS: The SF-1
      Gly146Ala variation may constitute a susceptible factor for development of type 2
      diabetes and impairment of insulin actions.

PMID- 16564600
TI  - Elucidating cis- and trans-regulatory variation using genetical genomics.
AB  - Genetic variation, through its effects on gene regulatory networks, has an
      important role in determining biologic phenotypes and disease susceptibility.
      Recent studies using segregating populations have characterized variation in gene
      expression resulting from genetic differences and have used well-established
      assays to identify many cis-acting polymorphisms. Although trans effects have
      been shown to be globally important, their individual effects are small, such
      that their genome-wide identification remains a challenge. Two recent studies
      using approaches capitalizing on intercrossed mouse strains and novel
      computational methods have yielded examples of trans-regulatory networks.

PMID- 16564601
TI  - An epidemiologic study of early onset lung cancer.
AB  - Using cases from an ongoing case-control study, we completed a case series
      analysis by comparing epidemiologic, clinical and survival characteristics among
      lung cancer patients characterized by age at diagnosis. Our sample included 230
      early onset lung cancer (EOLC) (all Caucasian and no older than 50 years of age
      at diagnosis) and 426 later-onset cases (LOLC) (all Caucasian and no younger than
      70 years of age at diagnosis) who were referred to The University of Texas M.D.
      Anderson Cancer Center, Houston between 1995 and 2004. Detailed lifestyle,
      exposure, clinical, survival and self-reported cancer family history data were
      available from personal interviews. We observed a higher proportion of never
      smokers (23.9%) for the EOLC cases as compared to the LOLC cases (17.6%) and a
      higher proportion of former smokers (59.4%) among the LOLC cases compared to EOLC
      cases (17.8%). Adenocarcinoma was the most common histology (55.2%) among the
      EOLC cases. More (83.4%) of the EOLC cases presented with stage 3 or 4 lung
      cancer compared to the LOLC cases (58.6%). Median (M) survival was 16.7 months
      among the EOLC cases (M = 19.2 months for the LOLC cases) and the 24-month
      survival rate was 20.6% for the EOLC cases and 29.5% for the LOLC cases. Female
      EOLC cases (M = 20.7 months) exhibited better survival than male EOLC cases (M =
      13.0 months, P = 0.004). EOLC cases diagnosed with squamous cell carcinoma had
      poorer survival (M = 8.2 months) compared to cases with other histologies (P <
      0.001). For both groups, higher stage at presentation was associated with poorer
      survival (P < 0.001). These findings support the need for further study in the
      characterization and identification of genetic factors that influence and
      modulate early onset lung cancer risk and outcome.

PMID- 16564602
TI  - The effect of a biofilm on solute diffusion in fractured porous media.
AB  - At sites in fractured rock where contamination has been exposed to the rock
      matrix for extended periods of time, the amount of contaminant mass residing in
      the matrix can be considerable. Even though it may be possible to diminish
      concentrations by the advection of clean water through the fracture features,
      back diffusion from mass held in the matrix will lead to a continuing source of
      contamination. In such an event, the development of a biofilm (a thin film of
      microbial mass) on the wall of the fractures may act to limit or prevent the back
      diffusion process. The objective of this preliminary study is to explore the
      influence imparted by the presence of a biofilm on the process of matrix
      diffusion. The investigation was conducted using radial diffusion cells
      constructed from rock core in which biofilm growth was stimulated in a central
      reservoir. Once biofilms were developed, forward diffusion experiments were
      conducted in which a conservative solute migrated from the central reservoir into
      the intact rock sample. Diffusion experiments were performed in a total of 11
      diffusion cell pairs where biofilm growth was stimulated in one member of the
      pair and inhibited in the other. The effect of the presence of a biofilm on
      tracer diffusion was determined by comparison of the diffusion curves produced by
      each cell pair. A semi-analytical model that accounts for the presence of a
      biofilm was used to investigate the effect of the biofilm on mass transfer due to
      changes in the effective porosity, effective diffusion coefficient, and the depth
      of penetration of the biofilm into the intact rock. The results show that the
      biofilm acted to plug the rock matrix, rather than forming a discrete layer on
      the reservoir surface. The reduction in effective porosity due to the biofilm
      ranged from 6% to 52% with the majority of the samples in the 30% to 50% range.
      Based on the present results, with more efficient biofilm stimulation, it is
      reasonable to assume that a more complete plugging of the microcrack porosity
      might be possible, leaving a much thicker and efficient barrier than could be
      achieved via a surface biofilm.

PMID- 16564603
TI  - Contribution of the diffusive exchange method to the characterization of pore
      water in consolidated argillaceous rocks.
AB  - Consolidated argillaceous rocks, potential host rocks for nuclear waste disposal,
      display particular properties (low water content, very small pore size) that
      require specific methods, especially for the characterization of their pore
      water. The diffusive exchange method was applied to the claystone of Tournemire
      by taking into account the effect of swelling or micro-cracks induced by
      drilling. The good agreement of diffusion parameters with those obtained from the
      through-diffusion method showed that the extent of this disturbance was low. This
      method led to stable isotope content values in pore-water in good agreement with
      those measured in the fracture fluids located in the vicinity, validating the
      method. On the contrary, the vacuum distillation technique gave a systematic
      depletion in heavy isotopes of water, probably induced by an incomplete
      extraction of pore-water. For the chloride tracer, the determination of the
      accessible porosity on each sample allowed the estimate of chloride concentration
      of pore-water to be improved, by taking into account all the petrophysical
      heterogeneities.

PMID- 16564604
TI  - Comparison of the microbicidal efficacy on germ carriers of several tertiary
      amine compounds with ortho-phthalaldehyde and Perasafe.
AB  - Several tertiary amine formulations have been marketed as high-level
      disinfectants (HLDs). This study compared some of these formulations with two
      accepted HLDs [ortho-phthalaldehyde (OPA) and Perasafe] by determining the
      bactericidal effect on 52 micro-organisms using a metallic germ carrier,
      determining the sporicidal effect using a commercial germ carrier (3M spores),
      and performing a corrosion test on surgical blades with human blood. OPA and
      Perasafe were significantly more effective than all the tertiary amines tested,
      and acted within a contact time of 10 min compared with 20 min for the other
      products. For Gram-negative micro-organisms, Instrunet FA showed no significant
      differences at 20 min compared with OPA and Perasafe at 10 min. The amines tested
      did not differ significantly in global bactericidal efficacy. Unlike the tertiary
      amines, OPA and Perasafe were effective against mycobacteria (15-min contact
      period), but were not sporicidal. All agents (except one tertiary amine) passed
      the corrosion test. In conclusion, OPA and Perasafe can be considered as HLDs.
      However, 15-20 min of contact is required and both products have disadvantages.

PMID- 16564605
TI  - The effects of training and detraining on memory, neurotrophins and oxidative
      stress markers in rat brain.
AB  - In the current investigation we tested how swimming training (T) (8 week, 5
      times/week, 2 h/day), and detraining (DT) affects brain functions and oxidative
      stress markers in rat brain. The free radical concentration, measured by electron
      paramagnetic resonance, decreased in brain of T and DT rats compared to controls
      (C). The level of brain-derived neurotrophic factor (BDNF) increased as a result
      of training, but decreased below the control level after 6 weeks of detraining.
      In addition, the concentration of nerve growth factor (NGF) also declined with
      DT. The passive avoidance test was used to assess the memory of rats, and
      training-induced improvement was observed but the enhancement disappeared with
      detraining. When the content of mitochondrial electron transport complexes, as a
      potent free radical generator, was evaluated by the blue native gel method, no
      significant alterations were observed. The repair of nuclear and mitochondrial 8
      oxodeoxyguanosine, as measured by the activity of OGG1, showed no significant
      difference. Therefore, the results suggest that regular exercise training
      improves memory, decreases the level of reactive oxygen species, and increase the
      production of BDNF and NGF. On the other hand, it appears that the beneficial
      effects of training are reversible in the brain, since detraining down-regulates
      the neurotrophin level, and memory. It is suggested that exercise training is
      more likely to beneficially effect the production of reactive oxygen species and
      the related oxidative damage.

PMID- 16564606
TI  - The live Mycobacterium tuberculosis phoP mutant strain is more attenuated than
      BCG and confers protective immunity against tuberculosis in mice and guinea pigs.
AB  - The Mycobacterium tuberculosis phoP mutant strain SO2 has previously been shown
      to have reduced multiplication in mouse macrophages and in vivo using the mouse
      intravenous-infection model. In this study we demonstrate that the M.
      tuberculosis SO2 is highly attenuated when compared with the parental M.
      tuberculosis MT103 strain and also more attenuated than BCG in severe combined
      immunodeficiency disease (SCID) mice. Complementation of the M. tuberculosis SO2
      with the wild-type phoP gene restored the virulence of the strain in the SCID
      mice, confirming that the attenuated phenotype is due to the phoP mutation. In
      Balb/c mice subcutaneously vaccinated with either M. tuberculosis SO2 or BCG, the
      proportions of CD4+ and CD8+ populations measured in the spleen were
      significantly higher in the M. tuberculosis SO2 vaccinated group. In addition,
      the proportion of antigen-stimulated CD4+/CD8+ cells expressing IFN-gamma was
      significantly higher in the M. tuberculosis SO2 vaccinated group when compared
      with the BCG group. Balb/c mice subcutaneously vaccinated with the M.
      tuberculosis SO2 strain were also protected against intra-venous challenge with
      M. tuberculosis H37Rv at levels comparable to mice vaccinated with BCG, as
      measured by reduced bacterial counts in lung and spleens. Guinea pigs
      subcutaneously vaccinated with the M. tuberculosis SO2 strain were protected
      against aerosol challenge with M. tuberculosis H37Rv delivered at different
      doses. A high dose aerosol challenge of M. tuberculosis SO2 vaccinated guinea
      pigs resulted in superior levels of protection when compared with BCG
      vaccination, as measured by guinea pig survival and reduction in disease severity
      in the lung.

PMID- 16564608
TI  - Residues of genotoxic alkyl mesylates in mesylate salt drug substances: real or
      imaginary problems?
AB  - Mesylate esters of short-chain (n = 1-3) alcohols are reactive, direct-acting,
      genotoxic and possibly carcinogenic alkylating agents. Their chemical and
      biological properties appear to correlate well with Swain-Scott s constants; for
      example, high S(N)1 character (low s value) is associated with enhanced
      carcinogenic potential, but also a rapid hydrolysis rate. Concerns over the
      possible formation of such esters during the preparation of mesylate salt drug
      substances, by addition of methane sulfonic acid (MSA) to the free base dissolved
      in an alcoholic solvent, have led regulatory agencies to require applicants to
      demonstrate that the synthetic method employed does not lead to the presence of
      detectable levels of alkyl mesylates. Mechanistic considerations, relating mainly
      to the extremely low nucleophilicity of the mesylate anion, and experimental
      data, both indicate that alkyl mesylates should not be formed (except from MSA
      impurities) during mesylate salt synthesis. Mechanistic arguments also predict
      that residues of alkyl halides (possibly formed in the preparation of amine
      hydrochlorides or hydrobromides) could represent a similar or greater potential
      hazard than alkyl mesylates. The perceived risk of alkyl mesylate formation seems
      to rely on mistaken assumptions and so the concerns appear unjustified. Further
      reassurance could be achieved however by applying a variety of strategies during
      synthesis, including pH control, and use of high-purity MSA or of a non
      hydroxylic reaction solvent.

PMID- 16564607
TI  - Environmental pollutants in endangered vs. increasing subspecies of the lesser
      black-backed gull on the Norwegian Coast.
AB  - Organochlorine (OC) residues were measured in eggs and blood of different
      subspecies of the lesser black-backed gull, Larus fuscus, on the Norwegian coast:
      a) increasing L. f. intermedius in the North Sea; b) endangered L. f. fuscus near
      the Arctic Circle; c) L. f. fuscus and greyish-mantled gulls, with a L. f.
      intermedius appearance, in the Barents Sea region. The dominating OCs in lesser
      black-backed gulls were polychlorinated biphenyls (PCB) and p,p'
      dichlorodiphenyldichloroethylene (DDE). DDE and beta-hexachlorocyclohexane (beta
      HCH) residues were higher in L. f. fuscus compared to L. f. intermedius and
      greyish-mantled birds in the Barents Sea region. In the latter area, blood
      residues of PCB and DDE in lesser black-backed gulls were as high as in great
      black-backed gulls, Larus marinus, while in the other regions they were lower.
      The higher DDE residues in endangered L. f. fuscus compared to increasing L. f.
      intermedius and greyish-mantled birds, which are invading northern Norway,
      suggest that OCs may have played a role in the population decline of L. f.
      fuscus, possibly in combination with nutrient stress.

PMID- 16564609
TI  - The development and regulation of occupational exposure limits in Korea.
AB  - With the institution of the new chemical regulatory framework in 2003, chemicals
      at the workplace have been classified into five categories; banned substances,
      permission-required substances, regulated substances, occupational exposure limit
      set substances, and other generally controlled substances. Currently, there are
      698 substances with OELs. As we have come to gain our own experiences in the
      study and control of chemical hazards at the workplace such as the 2-bromopropane
      poisoning, OEL setting process has been streamlined. The OELs in Korea, however,
      remain merely as a recommendation, which does not require all the substances with
      OELs to be measured at the workplace. Coordination of whole program for hazardous
      chemicals including workplace measurement, OEL setting process, and enforcement
      activities is still needed in Korea.

PMID- 16564610
TI  - Diphenyl ditelluride- and methylmercury-induced hyperphosphorilation of the high
      molecular weight neurofilament subunit is prevented by organoselenium compounds
      in cerebral cortex of young rats.
AB  - Organotellurides are important intermediates in organic synthesis and,
      consequently, the occupational exposure to them is a constant risk for laboratory
      workers. These compounds can elicit many neurotoxic events in the central nervous
      system (CNS) that are associated with several neurological symptoms. In contrast,
      organoselenium compounds are considered to exert neuroprotective actions on such
      effects. Neurofilaments (NF) are important cytoskeletal proteins and
      phosphorylation/dephosphorylation of NF is important to stabilize the
      cytoskeleton. In this work we investigated the potential protective ability of
      the selenium compounds ebselen and diphenyl diselenide (PhSe)(2) against the
      effect of diphenyl ditelluride (PhTe)(2) and methylmercury (MeHg) on the total
      (phosphorylated plus nonphosphorylated) and phosphorylated immunocontent of the
      high molecular weight neurofilament subunit (NF-H) from slices of cerebral cortex
      of 17-day-old rats. We observed that 1muM MeHg induced hyperphosphorylation,
      increasing the total immunocontent of this subunit of the high-salt Triton
      insoluble NF-H. Otherwise, 15muM (PhTe)(2) induced hyperphosphorylation of the
      high-salt Triton insoluble NF-H without altering the total immunocontent of this
      protein into the cytoskeletal fraction. Concerning the selenium compounds, 15muM
      (PhSe)(2) and 5muM ebselen did not induce alteration per se on the in vitro
      phosphorylation of NF-H. In addition, (PhSe)(2) and ebselen at these
      concentrations, presented a protective effect against the action of (PhTe)(2) and
      MeHg, on the immunoreactivity of NF-H. Considering that hyperphosphorylation of
      NF-H is associated with neuronal dysfunction it is probable that the effects of
      (PhTe)(2) and MeHg could be related to the remarkable neurotoxicity of these
      organocalcogenides. Furthermore the neuroprotective action of selenium compounds
      against (PhTe)(2) and MeHg effects could be a promising route to be exploited for
      a possible treatment of calcogenides poisoning.

PMID- 16564611
TI  - Effects of melatonin and vitamin E on oxidative-antioxidative status in rats
      exposed to irradiation.
AB  - Bone marrow is known to be particularly susceptible to radiation. In this study,
      the effects of treatment with Vitamin E and melatonin and irradiation-induced
      lipid peroxidation and its association with antioxidant enzymes in the total bone
      (bone and bone marrow) and skeletal muscle of rats subjected to total body
      irradiation was investigated. Wistar-Albino rats were intraperitoneally treated
      with 100mg/kg Vitamin E or melatonin before exposure to 720cGy irradiation.
      Control, irradiation, Vitamin E plus irradiation, melatonin plus irradiation
      groups were sacrificed by decapitation under ether anaesthesia on the 10th day
      after irradiation exposure. Application of total body irradiation elevated
      malondialdehyde (MDA) levels in rat skeletal muscle (p<0.001), but glutathione
      peroxidase (GSH-Px) and catalase activities remained unchanged. Application of
      Vitamin E with irradiation or melatonin decreased the MDA levels in skeletal
      muscle (p<0.01), but did not affect the GSH-Px and catalase activity. MDA levels
      were found elevated in total bone (p<0.001), GSH-Px activity decreased (p<0.001)
      and catalase activity remained unchanged in the group treated with irradiation.
      Application of Vitamin E with irradiation increased the GSH-Px activity in total
      bone (p<0.01), but the activity of MDA and catalase remained unchanged. Treatment
      of the animals with melatonin concurrent with total body irradiation reduced the
      degree of lipid peroxidation and elevation in antioxidant enzymes in total bone
      (p<0.01). We conclude that melatonin may protect the total bone from the damaging
      effects of irradiation exposure, and its actions protect total bone from
      oxidative stress. However, protective effects of Vitamin E were not observed in
      this study.

PMID- 16564612
TI  - A hand-over-hand diffusing model for myosin-VI molecular motors.
AB  - Single molecules of dimeric myosin-VI have been demonstrated to be able to move
      processively towards the pointed end of actin filament with a mean step size of
      approximately 36 nm. Here we present a hand-over-hand diffusing mechanism for
      this unidirectional movement. Based on this mechanism, its dynamical behaviors
      such as the step-size distribution, dwell-time distributions and mean dwell time
      at various ATP and ADP concentrations and under various loads are studied in
      detail. The calculated results show good agreement with previous experimental
      results. The processive movement of mutant myosin-V with its neck domains
      truncated to only one IQ motif can also be explained by using this hand-over-hand
      diffusing model.

PMID- 16564613
TI  - Use of GIS in siting stabilization pond facilities for domestic wastewater
      treatment.
AB  - Geographic information systems (GIS) use is presented in the problem of sitting
      areas for construction of natural systems such as stabilization ponds (SPs) for
      domestic wastewater treatment. For this purpose, several variables, such as
      topography, land use, type of geological formation, distance to major rivers or
      lakes, distance to existing cities and villages, existence of environmentally
      protected areas, mean minimum monthly temperatures and required wastewater
      effluent characteristics were analyzed with the GIS, in order to accept or reject
      a particular area within a region. The method is applied in the region of Thrace
      (Northeast Greece) at the municipal level. The required area for SP systems was
      calculated in each of the 36 municipalities of Thrace (including two islands,
      Thassos and Samothraki) as a function of the population of each municipality,
      temperature and local wastewater effluent discharge criteria. Based on the GIS
      analysis, suitable locations were identified in each municipality first, and then
      the total required surface area of these systems was compared to the available
      surface area of each municipality, in order to decide whether SP systems could be
      a viable solution to the wastewater management problem in the particular region.
      In that way the present methodology offers a fast and simple method to check the
      suitability of new areas for construction of such systems.

PMID- 16564614
TI  - Positive surgical margins in robotic-assisted radical prostatectomy: impact of
      learning curve on oncologic outcomes.
AB  - OBJECTIVE: The presence of positive surgical margins following radical
      prostatectomy is a known risk factor for disease recurrence and may lead to
      adjuvant treatment. Our goal was to assess the incidence of positive surgical
      margins in our series of robotic-assisted radical prostatectomy (RARP) and its
      relationship to our learning curve. METHODS: Between February 2003 and August
      2005, 140 patients underwent RARP by the same surgical team at our institution.
      The records of our first 100 consecutive RARPs were retrospectively reviewed. The
      patients were divided into three groups based on the time of surgery: group I
      included the first 33 cases; group II included the second 33 cases; and group III
      comprised the last 34 cases. We compared the incidence and location of positive
      surgical margins among the groups. Additional variables evaluated included the
      patient's prostate-specific antigen (PSA) level, preoperative/postoperative
      Gleason score, clinical/pathologic stage, and pathologic tumour volume. RESULTS:
      The positive margin rates were 45.4%, 21.2%, and 11.7% for groups I, II, and III,
      respectively. The difference in positive margin rates in the three groups was
      statistically significant (p=0.0053). Positive margin rates declined specifically
      at the apex and bladder neck when comparing the first 33 patients to the last 34
      patients. Patient demographics and preoperative staging variables were comparable
      among all three groups, with no statistically significant differences among them.
      CONCLUSIONS: This study illustrates that experience gained with time led to a
      decrease in the incidence of positive surgical margins. We do not feel that a
      selection bias affected our results because clinical and pathologic staging was
      evenly distributed within the three study groups. A steady reduction in positive
      surgical margin rates demonstrates a learning curve, of approximately 30
      patients, associated with RARP, and suggests that oncologic outcome is affected
      by the experience of the robotic surgeon.

PMID- 16564615
TI  - A hospital-based study: risk factors in development of motor complications in 555
      Parkinson's patients on levodopa therapy.
AB  - OBJECTIVES: Although levodopa (LD) is the gold standard therapy for symptomatic
      treatment of Parkinson's disease (PD), the chronic use of LD leads to the
      development of motor complications in almost all patients. PATIENTS AND METHODS:
      We assessed the presence and risk factors for motor complications in PD patients
      on LD therapy. We examined 555 PD patients on LD for the presence or absence of
      wearing-off (WO+/-) and dyskinesia (DK+/-). RESULTS: WO was present in 46.3%, and
      DK in 30.1% of patients. The mean age at onset of symptoms were earlier in
      WO(+)/DK(+) groups (p<0.001). The duration of PD was longer in WO(+)/DK(+) groups
      (p<0.001). The time between the first symptom and the occurrence of WO/DK, or LD
      initiation were not significantly different. The initial LD dose was
      significantly higher in WO(+) compared to WO(-) (300.1mg/d versus 232.5mg/d,
      p<0.001), and DK(+) compared to DK(-) groups (291.4 mg/d versus 251.9 mg/d,
      p=0.001). The time until dopamine agonist (DA) initiation was longer in
      WO(+)/DK(+) groups (p<0.001). WO (p<0.001) and DK (p=0.002) were more common in
      patients with H&Y stages 3+4. UPDRS scores were higher in WO(+) and DK(+)
      patients (p<0.001 and p=0.027). CONCLUSION: Our study showed that the development
      of motor complications was associated with early onset PD, longer disease
      duration, advanced disease, higher initial LD dose, longer LD use, and late DA
      initiation, but not with the timing of LD initiation.

PMID- 16564616
TI  - Oxidative burst of neutrophils against melanoma B16-F10.
AB  - Intensive oxidative burst was determined by chemiluminescence of peripheral blood
      neutrophils of mice that were intramuscularly injected with melanoma B16-F10
      and/or subcutaneously with Sephadex G-200. The neutrophils from papula developed
      at the site of Sephadex injection were cytotoxic for the B16-F10 cells in vitro.
      However, survival of Sephadex injected tumour-bearing mice was lower than of
      control animals bearing B16-F10, while their tumours grew faster and were less
      necrotic. Thus, it is likely that injection of Sephadex distracted the
      neutrophils from the tumour allowing faster progression of the tumour, indicating
      that neutrophils may have an important role in the host defence against malignant
      cells in the early stage of tumour development.

PMID- 16564617
TI  - Angiogenesis and antiangiogenic therapy in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a hypervascular tumor characterized by
      neovascularization, which plays an important role in the growth and progression
      of HCC. Angiogenesis provides a target for novel prognostic and therapeutic
      approaches to HCC. Assessment of microvessel density using immunohistochemical
      staining for specific endothelial cell markers such as CD34 has been shown to
      provide prognostic information independent of conventional pathological
      parameters in HCC patients. Recent studies have unveiled the important angiogenic
      factors involved in the regulation of angiogenesis in HCC, although the exact
      molecular pathways are far from clear. Current data suggest that vascular
      endothelial growth factor (VEGF) plays a critical role in angiogenesis of HCC.
      Tumor expression of VEGF has been shown to correlate with tumor invasiveness and
      prognosis in patients with HCC. VEGF is an important molecular target for
      antiangiogenic therapy. Studies in animal models have demonstrated the efficacy
      of antiangiogenic agents such as anti-VEGF antibody and antagonists of VEGF
      receptors in suppressing hepatocarcinogenesis and growth of HCC. Antiangiogenic
      therapy has already entered clinical trials in HCC patients and holds the promise
      of providing an effective novel treatment for HCC, which is of great clinical
      significance because there is no existing effective systemic therapy for HCC.

PMID- 16564618
TI  - A sham-controlled, phase II trial of transcranial direct current stimulation for
      the treatment of central pain in traumatic spinal cord injury.
AB  - Past evidence has shown that motor cortical stimulation with invasive and non
      invasive brain stimulation is effective to relieve central pain. Here we aimed to
      study the effects of another, very safe technique of non-invasive brain
      stimulation--transcranial direct current stimulation (tDCS)--on pain control in
      patients with central pain due to traumatic spinal cord injury. Patients were
      randomized to receive sham or active motor tDCS (2mA, 20 min for 5 consecutive
      days). A blinded evaluator rated the pain using the visual analogue scale for
      pain, Clinician Global Impression and Patient Global Assessment. Safety was
      assessed with a neuropsychological battery and confounders with the evaluation of
      depression and anxiety changes. There was a significant pain improvement after
      active anodal stimulation of the motor cortex, but not after sham stimulation.
      These results were not confounded by depression or anxiety changes. Furthermore,
      cognitive performance was not significantly changed throughout the trial in both
      treatment groups. The results of our study suggest that this new approach of
      cortical stimulation can be effective to control pain in patients with spinal
      cord lesion. We discuss potential mechanisms for pain amelioration after tDCS,
      such as a secondary modulation of thalamic nuclei activity.

PMID- 16564619
TI  - Increased sensitivity of desensitized TRPV1 by PMA occurs through PKCepsilon
      mediated phosphorylation at S800.
AB  - Important mechanisms that regulate inhibitory and facilitatory effects on TRPV1
      mediated nociception are desensitization and phosphorylation, respectively. Using
      Ca2+-imaging, we have previously shown that desensitization of TRPV1 upon
      successive capsaicin applications was reversed by protein kinase C activation in
      dorsal root ganglion neurons and CHO cells. Here, using both Ca2+-imaging and
      patch-clamp methods, we show that PMA-induced activation of PKCepsilon is
      essential for increased sensitivity of desensitized TRPV1. TRPV1 has two putative
      substrates S502 and S800 for PKCepsilon-mediated phosphorylation. Patch-clamp
      analysis showed that contribution of single mutant S502A or S800A towards
      increased sensitivity of desensitized TRPV1 is indistinguishable from that
      observed in a double mutant S502A/S800A. Since S502 is a non-specific substrate
      for TRPV1 phosphorylation by kinases like PKC, PKA or CAMKII, evidence for a role
      of PKC specific substrate S800 was investigated. Evidence for in vivo
      phosphorylation of TRPV1 at S800 was demonstrated for the first time. We also
      show that the expression level of PKCepsilon paralleled the amount of
      phosphorylated TRPV1 protein using an antibody specific for phosphorylated TRPV1
      at S800. Furthermore, the anti-phosphoTRPV1 antibody detected phosphorylation of
      TRPV1 in mouse and rat DRG neurons and may be useful for research regarding
      nociception in native tissues. This study, therefore, identifies PKCepsilon and
      S800 as important therapeutic targets that may help regulate inhibitory effects
      on TRPV1 and hence its desensitization.

PMID- 16564620
TI  - Vasoactive intestinal peptide (VIP) is a modulator of joint pain in a rat model
      of osteoarthritis.
AB  - Osteoarthritis (OA) is a debilitating disease in which primarily weight-bearing
      joints undergo progressive degeneration. Despite the widespread prevalence of OA
      in the adult population, very little is known about the factors responsible for
      the generation and maintenance of OA pain. Vasoactive intestinal peptide (VIP)
      was identified in the synovial fluid of arthritis patients nearly 20 years ago
      and the aim of this study was to examine whether VIP could be involved in the
      generation of OA pain. Hindlimb weight bearing was used as a measure of joint
      pain, while von Frey hair algesiometry applied to the plantar surface of the
      ipsilateral hindpaw tested for secondary mechanical hyperalgesia. Intra-articular
      injection of VIP into normal rat knee joints caused a significant shift in weight
      bearing in favour of the contralateral non-injected hindlimb as well as causing a
      reduction in ipsilateral paw withdrawal threshold. These pain responses were
      blocked by co-administration of the VPAC receptor antagonist VIP6-28. Induction
      of OA by intra-articular sodium monoiodoacetate injection resulted in a reduction
      in weight bearing on the affected leg, but no evidence of secondary hyperalgesia
      in the paw. Treatment of OA knees with a single injection of VIP6-28 diminished
      hindlimb incapacitance while increasing paw withdrawal threshold. This study
      showed for the first time that peripheral application of VIP causes increased
      knee joint allodynia and secondary hyperalgesia. Furthermore, antagonists that
      inhibit VIP activity may prove beneficial in the alleviation of OA pain.

PMID- 16564621
TI  - Effect of local anesthesia on atypical odontalgia--a randomized controlled trial.
AB  - The aim of the study was to evaluate the analgesic effect of lidocaine in a
      double-blind, controlled multi-center study on patients with atypical odontalgia
      (AO)--a possible orofacial neuropathic pain condition. Thirty-five consecutive AO
      patients (range 31-81 years) with a mean pain duration of 7.2 years (range 1-30
      years) were recruited from four different orofacial pain clinics in Sweden. In a
      randomized cross-over design, 1.5 ml local anesthesia (20mg/ml lidocaine and 12.5
      microg/ml adrenaline) or 1.5 ml saline (9 mg/ml NaCl solution) (placebo) was
      injected to block the painful area. The VAS pain scores showed an overall effect
      of time (ANOVA: P<0.001) and treatment (ANOVA: P=0.018) with a significant
      interaction between the factors (ANOVA: P<0.001). Overall, VAS pain relief was
      significantly greater at 15-120 min following the lidocaine injections compared
      to the placebo injections (Tukey: P<0.05). All patients demonstrated significant
      disturbances in somatosensory function on the painful side compared to the non
      painful side as revealed by quantitative sensory tests, however, only one
      significant inverse correlation was found between percentage pain relief and the
      magnitude of brush-evoked allodynia (Spearman: P<0.01). In conclusion, AO
      patients experienced significant, but not complete, pain relief from
      administration of local anesthetics compared with placebo. The findings indicate
      that the spontaneous pain in AO patients only to some extent is dependent on
      peripheral afferent inputs and that sensitization of higher order neurons may be
      involved in the pathophysiology of AO.

PMID- 16564623
TI  - New insights into the therapeutic potential of non-invasive transcranial cortical
      stimulation in chronic neuropathic pain.

PMID- 16564624
TI  - Comments on Pud and Sapir study.

PMID- 16564622
TI  - Contribution of the ventromedial hypothalamus to generation of the affective
      dimension of pain.
AB  - The ventromedial hypothalamus (VMH) is a core structure underlying the generation
      of affective behaviors to threats. The prototypical threat to an individual is
      exposure to a noxious stimulus and the dorsomedial division of the VMH (dmVMH)
      receives nociceptive input. The present study evaluated the contribution of the
      dmVMH to generation of the affective reaction to pain in rats. Noxious tailshock
      elicits from rats vocalization afterdischarges (VADs) that have distinct
      spectrographic characteristics and are a validated model of the affective
      reaction to pain. VAD-like vocalizations (vocalizations with the same spectral
      characteristics of VADs) were elicited by stimulation (electrical or chemical) of
      the dmVMH. Stimulation in the vicinity of the dmVMH was ineffective in eliciting
      VADs. Manipulation of GABA(A) neurochemistry within the dmVMH altered the
      threshold for elicitation of VADs by dmVMH stimulation or tailshock.
      Administration of the GABA(A) antagonist bicuculline or the GABA(A) agonist
      muscimol into the dmVMH lowered and elevated VAD thresholds, respectively. These
      treatments did not alter thresholds of other tailshock elicited responses
      (vocalizations during tailshock or spinal motor reflexes). Bicuculline and
      muscimol administered into the dmVMH also elevated and lowered the asymptotic
      level of fear conditioning supported by dmVMH stimulation or tailshock. These
      findings demonstrate that the dmVMH contributes to the processing of pain affect
      and that the affective dimension of pain belongs to a broader class of sensory
      experience that represents threat to the individual.

PMID- 16564625
TI  - Loss of spinal mu-opioid receptor is associated with mechanical allodynia in a
      rat model of peripheral neuropathy.
AB  - The present study investigated whether the loss of spinal mu-opioid receptors
      following peripheral nerve injury is related to mechanical allodynia. We compared
      the quantity of spinal mu-opioid receptor and the effect of its antagonists, such
      as naloxone and CTOP, on pain behaviors in two groups of rats that showed
      extremely different severity of mechanical allodynia 2 weeks following partial
      injury of tail-innervating nerves. One group (allodynic group) exhibited robust
      signs of mechanical allodynia after the nerve injury, whereas the other group
      (non-allodynic group) showed little allodynia despite having suffered the same
      nerve injury. In addition, we investigated the quantity of spinal mu-opioid
      receptor and the effect of its antagonists on pain behaviors after the rats had
      recovered from mechanical allodynia 16 weeks following nerve injury.
      Immunohistochemical and Western blot analyses at 2 weeks after nerve injury
      indicated that spinal mu-opioid receptor content was more reduced in the
      allodynic group compared to the non-allodynic group. Intraperitoneal naloxone (2
      mg/kg, i.p.) and intrathecal CTOP (10 microg/rat, i.t.) administration
      dramatically induced mechanical allodynia in the non-allodynic group. However, as
      in naive animals, neither the loss of spinal mu-opioid receptors nor antagonist
      induced mechanical allodynia was observed in the rats that had recovered from
      mechanical allodynia. These results suggest that the loss of spinal mu-opioid
      receptors following peripheral nerve injury is related to mechanical allodynia.

PMID- 16564626
TI  - The tetrapartite synapse: path to CNS sensitization and chronic pain.

PMID- 16564627
TI  - The role of values in a contextual cognitive-behavioral approach to chronic pain.
AB  - Chronic pain can dominate all concerns for individuals suffering with it, leaving
      much of their time focused on trying to reduce pain rather than living their
      life, as they would most want to do, according to their values. The purpose of
      this study was to examine these processes, the degree of success patients have in
      following their values as guides for their actions, and relations between values
      based action and other aspects of daily functioning. For this study we designed a
      brief inventory of patient values in domains of family, intimate relations,
      friends, work, health, and growth or learning. One hundred forty, consecutive,
      adult patients referred to a pain management unit completed this inventory in
      addition to measures of pain, disability, depression, pain-related anxiety, and
      acceptance of pain. Results showed that highest importance was placed on values
      in the domains of family and health and the least importance in friends and
      growth or learning. Highest success was reported in domains of family and friends
      and the least success in health and growth or learning. Significant correlations
      of overall success with measures of avoidance and acceptance of pain supported
      the validity of scores from the values measure. Success in living according to
      values was correlated with measures of disability, depression, and pain-related
      anxiety. Regression analysis showed that success at living according to values
      predicted variance in functioning independent of acceptance of pain, supporting
      its incremental utility in a contextual analysis of chronic pain and its
      potential importance in treatment for chronic pain.

PMID- 16564629
TI  - Structure analysis of embedded nano-sized particles by precession electron
      diffraction. eta'-precipitate in an Al-Zn-Mg alloy as example.
AB  - The Vincent-Midgley precession technique has been used to collect three
      dimensional electron diffraction intensity data from a dispersion of coherent
      precipitates in a matrix. In order to suppress severe effects from multiple
      diffraction via matrix reflections, a fairly large precession (tilt) angle had to
      be used. This implied a high background from the surrounding matrix, and limited
      the number of reflections that could be measured from patterns on image plates.
      The heavily faulted hexagonal eta'-precipitates (a = 0.496 nm, c = 1.405 nm) with
      thickness 3-5 nm occur in four equivalent orientations relative to the aluminium
      matrix; with frequent overlap of reflections. A model of the average structure in
      the space group P6(3)/mmc with assumed composition Mg(2)Zn(5-x)Al(2+x), have been
      derived by Patterson analysis and intensity comparisons.

PMID- 16564630
TI  - The impact on database searching arising from inconsistency in the nomenclature
      of parasitic diseases.
AB  - The existing usage of disease names formed from the name of the parasite taxon is
      characterised by marked heterogeneity. This is largely due to the fact that, for
      coining disease names, four different suffixes, '-osis', '-iosis', '-asis' and '
      iasis', are being used inconsistently. The result is that alternative terms are
      in use for naming the same disease, e.g. trypanosomosis and trypanosomiasis,
      fasciolosis and fascioliasis, ascariosis and ascariasis. Inspite of the
      SNOAPAD/SNOPAD guideline (1988) which proposed the principles of a uniform and
      standard disease nomenclature, the actual usage depends largely on tradition,
      educational imprinting and personal preferences, showing great variation. By
      using alternative disease names as search terms the author investigates in four
      databases the impact of nomenclatural heterogeneity on information storage and
      retrieval. It is evident that the existence of alternative disease names in
      parasitology markedly interferes with the efficacy of online data retrieval. The
      value of a disease name as a search term was shown to be greatly different in
      various databases. Until we have to coexist with an inconsistent disease
      terminology we need to adopt specially structured database-search techniques to
      ensure a proper level of precision in searching. Such possible techniques are
      considered.

PMID- 16564631
TI  - Epidemiological investigations on Trichinella infections in farmed fur animals of
      Estonia.
AB  - Farming of fur animals represents an important income in Estonia. Even though
      Trichinella worms does not induce a symptomatic disease in carnivores, the
      carcasses of skinned animals can increase the biomass of the parasite in the
      environment, if they are not properly destroyed. The aim of the present survey
      was to study the prevalence of Trichinella worms in farmed fur animals of
      Estonia. Of 281 muscle samples from blue foxes (Alopex lagopus), silver foxes
      (Vulpes vulpes fulva), minks (Mustela vison) and raccoon dogs (Nyctereutes
      procyonoides), which were collected in eight farms, Trichinella larvae have been
      detected in 21 animals (8%) from two farms by HCl-pepsin digestion. The highest
      number of larvae per gram of muscle was found in the front limb muscles. Larvae
      of the 21 isolates have been identified as Trichinella britovi or Trichinella
      nativa by a multiplex-PCR analysis.

PMID- 16564632
TI  - Ribosome-inactivating proteins in edible plants and purification and
      characterization of a new ribosome-inactivating protein from Cucurbita moschata.
AB  - The basic protein fraction of tissue extracts from 40 edible plants inhibited
      cell-free protein synthesis and released adenine from herring sperm DNA, thus
      having adenine glycosylase activity. This suggested the presence of ribosome
      inactivating proteins (RIPs) in the plant extracts. This indication was further
      strengthened by the presence of the two activities after a partial
      chromatographic purification of three extracts, including that from Lycopersicon
      esculentum (tomato), which had very low activity. From the extract of Cucurbita
      moschata (pumpkin), the most active one, a glycoprotein of 30,665 Da was purified
      which had the properties of a RIP, in that (i) it inhibited protein synthesis by
      a rabbit reticulocyte lysate with IC50 (concentration giving 50% inhibition)
      0.035 nM (1.08 ng ml(-1)) and by HeLa, HT29 and JM cells with IC50 in the 100 nM
      range, (ii) deadenylated hsDNA and other polynucleotidic substrates, and (iii)
      depurinated yeast rRNA at a concentration of 0.1 ng ml(-1), all values being
      comparable to those of other RIPs. The C. moschata RIP gave a weak cross-reaction
      only with an antiserum against dianthin 32, but not with antisera against other
      RIPs, and had superoxide dismutase, antifungal and antibacterial activities.

PMID- 16564633
TI  - Diltiazem, a L-type calcium channel antagonist, suppresses ouabain-enhanced
      dopamine efflux by 1-methyl-4-phenylpyridinium ion (MPP+) in rat striatum.
AB  - The present study was examined whether diltiazem, a L-type Ca2+ channel
      antagonist, could suppresses 1 methyl-4-phenylpyridinium ion (MPP+)-induced
      dopamine (DA) in extracellular fluid of rat striatum. Ouabain (100 microM; 100
      microM or 100 pmol/microl per min) significantly enhanced the level of DA by
      MPP+. However, in the presence of diltiazem (100 microM) significantly suppressed
      the level of DA release by ouabain and MPP+. These results suggest that diltiazem
      suppresses Ca2+ -dependent release of DA by ouabain-induced Ca2+ overload.

PMID- 16564634
TI  - The aging hippocampus: a multi-level analysis in the rat.
AB  - In the current experiment we conducted a multi-level analysis of age-related
      characteristics in the hippocampus of young adult (3 months), middle-aged (12
      months), and old (24 months) Fisher 344xBrown Norway hybrid (FBNF1) rats. We
      examined the relationships between aging, hippocampus, and memory using a
      combination of behavioral, non-invasive magnetic resonance imaging and
      spectroscopy, and postmortem neuroanatomical measures in the same rats. Aging was
      associated with functional deficits on hippocampus-dependent memory tasks,
      accompanied by structural alterations observed both in vivo (magnetic resonance
      imaging-hippocampal volume) and postmortem (dentate gyrus neuronal density and
      neurogenesis). Neuronal metabolic integrity, assessed by levels of N
      acetylaspartate with magnetic resonance spectroscopy, was however, preserved.
      Further, our results suggest that neurogenesis (doublecortin) seems to be related
      to both performance deficits on hippocampus-dependent tasks and hippocampal
      volume reduction. The observed pattern of age-related alterations closely
      resembles that previously reported in humans and suggests FBNF1 rats to be a
      useful model of normal human aging.

PMID- 16564635
TI  - Frequency-dependent modulation of glycine receptor activation recorded from the
      zebrafish larvae hindbrain.
AB  - In vertebrates, most glycinergic inhibitory neurons discharge phasically at a
      relatively low frequency. Such a pattern of glycine liberation from presynaptic
      terminals may affect the kinetics of post-synaptic glycine receptors. To examine
      this influence, we have analyzed the behavior of glycine receptors in response to
      repetitive stimulation at frequencies at which consecutive outside-out currents
      did not superimpose (0.5-4 Hz). Neurotransmitter release was mimicked on outside
      out patches from zebrafish hindbrain Mauthner cells using fast flow application
      techniques. The amplitude of outside-out currents evoked by short (1 ms)
      repetitive applications of a saturating concentration (3 mM) of glycine remained
      unchanged for application frequencies<or=1 Hz. When the application frequency was
      increased from 1 to 4 Hz, the amplitude of the outside-out currents decreased
      with time to reach a steady state level. This decrease in current amplitude was
      larger and occurred faster with increasing application frequencies. Recovery
      occurred when the stimulation frequency was decreased back to 1 Hz. The recovery
      time constant was independent on the application frequency. This frequency
      dependent inhibition was also observed for non-saturating glycine concentrations.
      Our results indicate that glycine receptor activity is down-regulated when the
      stimulation frequency increases to values>1 Hz. Glycine-evoked current
      simulations using a simple Markov model describing zebrafish glycine receptor
      kinetic behavior, indicates that this down-regulation of glycine receptor
      efficacy is due to a progressive accumulation of the receptors in a long lasting
      desensitization state. Our simulations suggest that this down-regulation can
      occur even when spontaneous inhibitory currents were generated randomly at a
      frequency>1 Hz.

PMID- 16564637
TI  - Relative roles of protein kinase A and protein kinase C in modulation of
      transient receptor potential vanilloid type 1 receptor responsiveness in rat
      sensory neurons in vitro and peripheral nociceptors in vivo.
AB  - The function of the transient receptor potential vanilloid type 1 capsaicin
      receptor is subject to modulation by phosphorylation catalyzed by various enzymes
      including protein kinase C and cAMP-dependent protein kinase. The aim of this
      study was to compare the significance of the basal and stimulated activity of
      protein kinase C and cAMP-dependent protein kinase in transient receptor
      potential vanilloid type 1 receptor responsiveness in the rat in vitro by
      measurement of the intracellular calcium concentration in cultured trigeminal
      ganglion neurons and in vivo by determination of the behavioral noxious heat
      threshold. KT5720, a selective inhibitor of cAMP-dependent protein kinase,
      reduced the calcium transients induced by capsaicin or the other, much more
      potent transient receptor potential vanilloid type 1 receptor agonist
      resiniferatoxin in trigeminal sensory neurons and diminished the drop of the
      noxious heat threshold (heat allodynia) evoked by intraplantar resiniferatoxin
      injection. Chelerythrine chloride, a selective inhibitor of protein kinase C,
      failed to alter either of these responses, although it inhibited the effect of
      phorbol 12-myristate 13-acetate in the in vitro assay. Staurosporine, a rather
      nonselective protein kinase inhibitor, failed to reduce the capsaicin- and
      resiniferatoxin-induced calcium transients but inhibited the resiniferatoxin
      evoked heat allodynia. Dibutyryl-cAMP and phorbol 12-myristate 13-acetate,
      activator(s) of cAMP-dependent protein kinase and protein kinase C, respectively,
      enhanced the effect of capsaicin in the calcium uptake assay while forskolin, an
      activator of adenylyl cyclase, augmented that of resiniferatoxin in the heat
      allodynia model. None of the protein kinase inhibitors or activators altered the
      calcium transients evoked by high potassium, a nonspecific depolarizing stimulus.
      It is concluded that basal activity of cAMP-dependent protein kinase, unlike
      protein kinase C, is involved in the maintenance of transient receptor potential
      vanilloid type 1 receptor function in somata of trigeminal sensory neurons but
      stimulation of either cAMP-dependent protein kinase or protein kinase C above the
      resting level can lead to an enhanced transient receptor potential vanilloid type
      1 receptor responsiveness. Similar mechanisms are likely to operate in vivo in
      peripheral terminals of nociceptive dorsal root ganglion neurons.

PMID- 16564636
TI  - The anti-invasive compound motuporamine C is a robust stimulator of neuronal
      growth cone collapse.
AB  - Neuronal outgrowth is a fundamental process for normal development of the nervous
      system. Despite recent advances, the molecular mechanisms governing neuronal
      motility are still poorly understood. To provide insight into the intracellular
      signaling mechanisms required for neuronal outgrowth, we have characterized the
      effects of a compound previously identified for its anti-motility effects on
      transformed cells. We show that this compound, motuporamine C, acts as a robust
      inhibitor of chick neurite outgrowth in a dose-dependent fashion. Furthermore, in
      the presence of motuporamine C, growth cone collapse is observed, followed by
      neurite retraction. After removal, growth cones re-extend lamellipodial and
      filopodial processes and re-establish motility. Neurons exposed to motuporamine C
      exhibit a significant upregulation of active Rho-GTP. Additionally, effector
      blocking experiments using Rho and Rho-associated kinase inhibitors indicate that
      the Rho pathway plays a critical role in motuporamine C-mediated growth cone
      collapse. Thus, we have characterized a novel anti-motility compound that has a
      robust inhibitory effect on neuronal outgrowth and involves signaling through the
      Rho-Rho kinase collapse pathway. Due to these robust effects, motuporamine C may
      serve as a valuable tool in further examining the intracellular mechanisms
      associated with growth cone motility.

PMID- 16564638
TI  - Induction of brain-derived neurotrophic factor by leptin in the ventromedial
      hypothalamus.
AB  - Leptin, an adipocyte-derived hormone, reduces food intake by regulating
      orexigenic and anorexigenic factors in the hypothalamus. Although brain-derived
      neurotrophic factor is an important anorexigenic factor in the hypothalamus,
      little is known about the regulation of brain-derived neurotrophic factor
      expression by leptin in the hypothalamus. In the present study, we examined the
      effect of leptin on the expression of brain-derived neurotrophic factor in the
      hypothalamus. I.V. administration of leptin (10 microg/g) led to the increase in
      the expression of brain-derived neurotrophic factor mRNA, which was observed in
      the dorsomedial part of the ventromedial hypothalamic nucleus. The increased
      expression of brain-derived neurotrophic factor mRNA was detected in
      phosphorylated signal transducer and activator of transcription 3-positive
      neurons, suggesting that leptin induced brain-derived neurotrophic factor
      expression in neurons of the dorsomedial part of the ventromedial hypothalamic
      nucleus. In addition, the expression of brain-derived neurotrophic factor was
      increased at the protein level in the ventromedial hypothalamic nucleus of leptin
      injected mice. Interestingly, brain-derived neurotrophic factor-positive fibers
      also increased in the ventromedial hypothalamic nucleus and dorsomedial
      hypothalamic nucleus of leptin-injected mice, which were in close apposition to
      tyrosine kinase receptor B-immunoreactive neurons and colocalized with
      synaptophysin, a marker of presynaptic terminals. These results suggest that
      leptin induces brain-derived neurotrophic factor expression in the dorsomedial
      part of the ventromedial hypothalamic nucleus and brain-derived neurotrophic
      factor may exert as anorexigenic factors possibly through the activation of
      tyrosine kinase receptor B in the ventromedial hypothalamic nucleus and
      dorsomedial hypothalamic nucleus.

PMID- 16564639
TI  - SK Ca2+-activated K+ channel ligands alter the firing pattern of dopamine
      containing neurons in vivo.
AB  - Apamin-sensitive, SK channels play an important role in generating the rhythmic
      firing patterns exhibited by midbrain dopamine neurons in vitro. However, their
      contribution to the firing properties of these cells in intact animals has yet to
      be determined. In the present series of experiments, extracellular single unit
      recording techniques were used to assess the central effects of prototypical SK
      channel ligands on the firing pattern of dopamine neurons in the substantia nigra
      of the chloral hydrate anesthetized rat. I.v. administration of the SK channel
      blocker apamin (0.4 mg/kg), increased bursting activity in approximately 50% of
      the dopamine neurons tested without altering average firing rate. The majority of
      these cells responded slowly to the effects of apamin, gradually transitioning
      from an irregular single spike to a phasic discharge composed of the same
      relative proportion of long (>or=three spike) and short (two spike) bursts as
      "natural" bursting activity recorded in drug naive animals. Local administration
      of apamin increased bursting activity in all cells tested. Systemic
      administration of the SK channel opener, 1-ethyl-2-benzimidazolinone (5-25 mg/kg)
      also had no effect on average firing rate but suppressed bursting activity and
      increased the precision of firing. The effects of 1-ethyl-2-benzimidazolinon on
      firing pattern were abolished when recording electrodes contained apamin (125
      microM). These results suggest that SK channels actively contribute to the
      spontaneous firing patterns exhibited by dopamine neurons in vivo and provide
      additional support for the proposition that this channel could serve as a useful
      target for modifying their activity.

PMID- 16564640
TI  - Transient receptor potential vanilloid 1-immunopositive neurons in the mouse are
      more prevalent within colon afferents compared to skin and muscle afferents.
AB  - Previous studies in our laboratories found that isolectin B(4)(IB(4))-positive
      polymodal nociceptors in the mouse do not express transient receptor potential
      vanilloid 1 (TRPV1), nor does deletion of TRPV1 compromise the ability of these
      afferents to detect thermal stimuli. Considering that IB(4)-positive afferents
      account for over 70% of cutaneous nociceptors and that 30-50% of all mouse
      primary afferents express TRPV1, it is highly likely that many TRPV1-positive
      fibers project to non-cutaneous structures. To investigate this issue, Alexa
      Fluor-conjugated wheat germ agglutinin (WGA) or IB(4) was injected into the
      nerves innervating quadriceps muscle (femoral) or hindlimb skin (saphenous) of
      male C57Bl/6 mice. Similarly, Alexa Fluor-conjugated cholera toxin-beta was
      injected subserosally into the distal colon. Spinal ganglia at the appropriate
      level (L2-3 for saphenous and femoral nerves; L6 for colon) were processed for
      TRPV1, calcitonin gene-related peptide (CGRP), neurofilament heavy chain (NHF)
      and IB(4) visualization and examined on a confocal microscope. Colon afferents
      contained the highest percentage of both TRPV1- and CGRP-positive neurons,
      followed by femoral (WGA) and saphenous afferents (WGA and IB(4)). In contrast,
      NHF staining was more prevalent among femoral afferents, followed by saphenous
      (WGA) and colon afferents. IB(4) binding was observed in very few colon or
      saphenous (WGA) afferents, with no femoral afferents binding or transporting
      IB(4). Considering that the largest percentages of TRPV1-positive neurons
      observed in this study were within visceral and muscle afferent populations
      (neurons that typically are not subject to noxious temperatures), these results
      suggest that TRPV1 may not function primarily as a temperature sensor but rather
      as a detector of protons, vanilloid compounds or through interactions with other
      membrane proteins.

PMID- 16564641
TI  - Limited influence of olanzapine on adult forebrain neural precursors in vitro.
AB  - We evaluated the activity of the atypical antipsychotic drug olanzapine on
      differentiation and gene expression in adult neural precursor cells in vitro.
      Neural precursors obtained from forebrain subventricular zone (SVZ)-derived
      neurospheres express a subset (13/24) of receptors known to bind olanzapine at
      high to intermediate affinities; in contrast, all 24 are expressed in the SVZ. In
      the presence of 10 nM, 100 nM or 1 microM olanzapine, there is no significant
      change in the frequency of oligodendrocytes, neurons, GABAergic neurons and
      astrocytes generated from neurosphere precursors. In parallel, there is no
      apparent change in cell proliferation in response to olanzapine, based upon
      bromodeoxyuridine incorporation. There are no major changes in cytological
      differentiation in response to the drug; however, at one concentration (10 nM)
      there is a small but statistically significant increase in the size of glial
      fibrillary acidic protein-labeled astrocytes derived from neurosphere precursors.
      In addition, olanzapine apparently modulates expression of one serotonin receptor
      -- 5HT2A -- in differentiating neurosphere cultures; however, it does not modify
      expression of several other receptors or schizophrenia vulnerability genes. Thus,
      olanzapine has a limited influence on differentiation and gene expression in
      adult neural precursor cells in vitro.

PMID- 16564642
TI  - Deletion of the neuropeptide Y Y1 receptor affects pain sensitivity, neuropeptide
      transport and expression, and dorsal root ganglion neuron numbers.
AB  - Neuropeptide Y has been implicated in pain modulation and is substantially up
      regulated in dorsal root ganglia after peripheral nerve injury. To identify the
      role of neuropeptide Y after axotomy, we investigated the behavioral and
      neurochemical phenotype of neuropeptide Y Y1 receptor knockout mice with focus on
      dorsal root ganglion neurons and spinal cord. Using a specific antibody Y1
      receptor immunoreactivity was found in dorsal root ganglia and in dorsal horn
      neurons of wild-type, but not knockout mice. The Y1 receptor knockout mice
      exhibited a pronounced mechanical hypersensitivity. After sciatic nerve axotomy,
      the deletion of Y1 receptor protected knockout mice from the axotomy-induced loss
      of dorsal root ganglion neurons seen in wild-type mice. Lower levels of
      calcitonin gene-related peptide and substance P were identified by
      immunohistochemistry in dorsal root ganglia and dorsal horn of knockout mice, and
      the axotomy-induced down-regulation of both calcitonin gene-related peptide and
      substance P was accentuated in Y1 receptor knockout. However, the transcript
      levels for calcitonin gene-related peptide and substance P were significantly
      higher in knockout than in wild-type dorsal root ganglia ipsilateral to the
      axotomy, while more calcitonin gene-related peptide- and substance P-like
      immunoreactivity accumulated proximal and distal to a crush of the sciatic nerve.
      These results indicate that the deletion of the Y1 receptor causes increased
      release and compensatory increased synthesis of calcitonin gene-related peptide
      and substance P in dorsal root ganglion neurons. Together, these findings suggest
      that, after peripheral nerve injury, neuropeptide Y, via its Y1 receptor
      receptor, plays a key role in cell survival as well as in transport and synthesis
      of the excitatory dorsal horn messengers calcitonin gene-related peptide and
      substance P and thus may contribute to pain hypersensitivity.

PMID- 16564643
TI  - Underreporting of illicit drug use by patients at emergency departments as
      revealed by two-tiered urinalysis.
AB  - This study investigates the validity of questionnaire-based self-reports of
      illicit drug use by comparing with a two-tiered urinalysis among patients at
      emergency departments. Questions on the use of alcohol and drugs were
      administered to patients recruited on a continual basis for 2weeks at the
      emergency department of two hospitals in northern Taiwan. Positive tests of
      initial urinalysis using fluorescence polarization immunoassay were further
      confirmed by gas chromatography/mass spectrometry. In a total of 1502 patients
      interviewed, 632 (42%) also provided a urine sample. Among those with urine
      samples, the positive rate of urinalysis was 1.4% for amphetamine-type drugs and
      1.6% for opiates. Among those with positive urinalysis, a false-negative rate
      ranged from 66.6% for amphetamines to 70.0% for opiates. Meanwhile, all the self
      reported current uses of either amphetamines or opiates were confirmed by
      urinalysis. The results indicate that the false-negative rates of questionnaire
      based, self-reported current use of illicit drug are around two thirds and the
      false-positive rates are negligible, which might be useful for the calibration of
      estimates from epidemiological surveys.

PMID- 16564644
TI  - Primary alcohol versus primary drug use among adolescents: an examination of
      differences.
AB  - Examination of differences between primary alcohol and drug abusing adolescents
      can provide valuable direction to intervention efforts, though little research in
      this area has been conducted. The current study compared primary alcohol and
      primary drug abusing runaway adolescents who were randomly assigned to family
      therapy or treatment as usual. Baseline differences, as well as response to
      treatment, were examined separately for alcohol and drug use and by gender.
      Although few baseline differences were found, hierarchical linear modeling
      indicated that alcohol and drug abusing male and female adolescents responded
      differently to therapy. Primary drug using males showed poorer alcohol use
      outcomes than did primary alcohol abusers. Specifically, alcohol use increased
      for primary drug using males receiving family therapy, while drug use decreased
      in all groups. Findings suggest that alcohol and drug use outcomes might be
      improved at treatment planning through consideration of client's gender and
      primary alcohol versus drug use.

PMID- 16564645
TI  - Novel electrochemical approach to enhanced toxicity of 4-oxo-2-nonenal vs. 4
      hydroxy-2-nonenal (role of imine): oxidative stress and therapeutic modalities.
AB  - Reactive oxygen species (ROS) and oxidative stress (OS) have received increasing
      attention in connection with illness, disease, and aging. The OS results in
      widespread attack of body constituents, with unsaturated lipids, leading to
      hydroperoxides, being a focus of research. Subsequent decomposition yields
      various functionalized aldehydes, including 4-hydroxy-2-nonenal (HNE). OS linked
      to HNE is associated with various illnesses. Recently, much attention has been
      devoted to 4-oxo-2-nonenal (ONE), also a product from lipid hydroperoxide
      decomposition. ROS and OS are increasingly implicated in the mode of action of
      drugs and toxins. The preponderance of bioactive substances or their metabolites
      incorporate electron transfer (ET) functionalities, among which are imines or
      iminiums. Also, in this category are the less well-known alpha-dicarbonyls. ET
      moieties undergo redox cycling accompanied by generation of ROS.
      Electrochemistry, a neglected area, can provide valuable insight. If the
      reduction potential is more positive than -0.5 V, then ET reactions are a
      possibility in vivo. Both HNE and ONE participate in Michael addition reactions
      with protein nucleophiles. The process occurs at a faster rate with ONE due
      mainly to the high reactivity toward His and Cys. The greater toxicity of ONE vs.
      HNE may partly reflect this difference. Also, ONE forms Schiff base (imine) at a
      faster rate than HNE, which also may contribute to the difference in toxicity.
      Electrochemistry of alpha-dicarbonyls and their imine derivatives can elucidate
      basic mechanisms. Methylglyoxal possesses a reduction potential of -0.18 V,
      amenable to ET in vivo. Since ONE is a vinylog of methylglyoxal, redox cycling
      should be even more facile. Another model is diacetyl whose reduction potential
      is also favorable. In contrast, crotonaldehyde, a model for the HNE vinylog, is
      characterized by a quite negative reduction potential, unsuitable for ET;
      acrolein is included. Imines of alpha-dicarbonyls serve as models for Schiff
      bases from ONE. The diimines in acid have reduction potentials of -0.45 to -0.49
      V. Diacetyl monoxime, an oximino analog of the vinylogous ONE mono Schiff base,
      possesses a similar value. The ONE vinylogs should exhibit even better
      electrochemical characteristics. Thus, these neglected electrochemical properties
      can help rationalize the greater toxicity of ONE vs. HNE. Toxicity of the
      aldehydes may be countered by various approaches: formation of non-toxic imines,
      carboxylic acids, and Michael adducts. Genetic methods and AO therapy are
      treated.

PMID- 16564646
TI  - Pretreatment factors significantly influence quality of life in cancer patients:
      a Radiation Therapy Oncology Group (RTOG) analysis.
AB  - PURPOSE: The purpose of this analysis was to assess the impact of pretreatment
      factors on quality of life (QOL) in cancer patients. METHODS AND MATERIALS:
      Pretreatment QOL (via Functional Assessment of Cancer Therapy [FACT], version 2)
      was obtained in 1,428 patients in several prospective Radiation Therapy Oncology
      Group (RTOG) trials including nonmetastatic head-and-neck (n = 1139), esophageal
      (n = 174), lung (n = 51), rectal (n = 47), and prostate (n = 17) cancer patients.
      Clinically meaningful differences between groups were defined as a difference of
      1 standard error of measurement (SEM). RESULTS: The mean FACT score for all
      patients was 86 (20.7-112) with SEM of 5.3. Statistically significant differences
      in QOL were observed based on age, race, Karnofsky Performance Status, marital
      status, education level, income level, and employment status, but not by gender
      or primary site. Using the SEM, there were clinically meaningful differences
      between patients </=50 years vs. >/=65 years. Hispanics had worse QOL than
      whites. FACT increased linearly with higher Karnofsky Performance Status and
      income levels. Married patients (or live-in relationships) had a better QOL than
      single, divorced, or widowed patients. College graduates had better QOL than
      those with less education. CONCLUSION: Most pretreatment factors meaningfully
      influenced baseline QOL. The potentially devastating impact of a cancer
      diagnosis, particularly in young and minority patients, must be addressed.

PMID- 16564647
TI  - Securidacaxanthone A, a heptaoxygenated xanthone from Securidaca
      longepedunculata.
AB  - From the root bark of Securidaca longepedunculata, a heptaoxygenated xanthone (1)
      has been isolated as well as two known xanthones (2) and (3) and two salicylic
      acid derivatives (4) and (5). The structure of 1 has been elucidated from 1H and
      13C-NMR spectral data.

PMID- 16564648
TI  - Evaluation of Pluchea carolinensis extracts as antioxidants by the epinephrine
      oxidation method.
AB  - Many methods have been used to evaluate synthetic and natural products as
      hydroxyl radical scavengers. In this study a spectrophotometric method to
      evaluate the scavenger activity of the hydroxyl radical produced in Fenton
      reaction is proposed. The oxidation of l-epinephrine to adrenochrome permitted
      the detection of the hydroxyl radical by spectrophotometry and its possible
      scavenging by hydroquinone, a well known antioxidant. The method was used to
      evaluate the antioxidant activity of Pluchea carolinensis leaves.

PMID- 16564649
TI  - Reduction of instrumental discrimination performance by post-conditioning
      devaluation of discriminative stimulus: the effects of novelty in reinforcing
      outcome and extended training.
AB  - In three experiments the effects of post-conditioning pairings of a
      discriminative stimulus (Sd) with an illness-inducing agent (lithium chloride,
      LiCl) on subsequent discrimination performance in extinction and consumption of
      reinforcing outcome were investigated. Rats were trained to choose a correct
      lever to obtain food pellets, with a light presented on a bulb just above the
      correct lever serving for the Sd on each trial. After achievement of a criterion
      of the discrimination, animals received paired or unpaired presentations of the
      Sds and LiCl injection. In Experiment 1, in which a familiar outcome was given
      throughout the discrimination training, Sd-LiCl pairings did not reduce either
      lever-press performance during presentation of the Sds or amount of consumption
      of outcomes. On the other hand, in Experiment 2 where a novel outcome was
      introduced in the final two sessions of the discrimination training, subsequent
      Sd devaluation reduced lever-press performance during presentations of the Sds.
      Similar findings were obtained in Experiment 3, in which animals were given
      extended discrimination training with introduction of novel outcomes in the final
      two sessions. These findings suggest that a representation of the outcome, evoked
      by presentation of the Sd, and illness were associated in the course of Sd-LiCl
      pairings but only when a novel outcome was used.

PMID- 16564650
TI  - Towards the analysis of the genomes of single cells: further characterisation of
      the multiple displacement amplification.
AB  - The development of methods for the analysis and comparison of the nucleic acids
      contained in single cells is an ambitious and challenging goal that may provide
      useful insights in many physiopathological processes. We review here some of the
      published protocols for the amplification of whole genomes (WGA). We focus on the
      reaction known as Multiple Displacement Amplification (MDA), which probably
      represents the most reliable and efficient WGA protocol developed to date. We
      discuss some recent advances and applications, as well as some modifications to
      the reaction, which should improve its use and enlarge its range of applicability
      possibly to degraded genomes, and also to RNA via complementary DNA.

PMID- 16564651
TI  - Identification, isolation, and partial characterization of a novel Streptococcus
      uberis adhesion molecule (SUAM).
AB  - The ability to attach to the host cell surface has been considered an important
      virulence strategy in many bovine mammary gland pathogens, including
      Streptococcus uberis. Research conducted in our laboratory lead to the
      identification of an S. uberis adhesion molecule (SUAM) with affinity for bovine
      lactoferrin (LF) and delineation of its role in adherence of S. uberis to bovine
      mammary epithelial cells. Using a selected bacterial surface protein extraction
      protocol and affinity chromatography, a 112-kDa protein that had a similar
      molecular mass and the LF affinity as one of the identified S. uberis LBP
      described by Fang and Oliver in 1999 was found. To further characterize SUAM, the
      N-terminal amino acid sequence of this protein was elucidated. A protein query
      versus translated database TBLASTN search of the National Center for
      Biotechnology (NCBI), non-redundant database, nr, with the LBP N-terminal amino
      acid sequence showed no significant similarity with previous entries. Antibodies
      directed against SUAM and a 17 amino acid long N-terminal sequence (pep-SUAM)
      inhibited adherence to and internalization of S. uberis UT888 into bovine mammary
      epithelial cells. Data presented suggests that we have discovered a novel
      bacterial protein involved in the pathogenesis of this economically important
      mastitis pathogen.

PMID- 16564652
TI  - Plasmid DNA and siRNA transfection of intestinal epithelial monolayers by
      electroporation.
AB  - This study was conducted to evaluate the ability of electroporation to
      efficiently transfect differentiated intestinal epithelial monolayers with
      plasmid DNA and to determine whether electroporation can transfect these
      monolayers with short-interfering RNA (siRNA) to cause gene silencing. Confluent
      T84 monolayers were transfected with reporter plasmids expressing luciferase or
      green-fluorescent protein or with siRNA directed against the nuclear envelope
      proteins lamin A/C using electroporation. Optimized electroporation conditions
      resulted in luciferase and GFP expression. Both intracellular uptake of
      fluorescently labeled plasmid and expression of the reporter genes increased with
      increasing electroporation strength and DNA concentration. When monolayers were
      transfected by lipofection with the reporter plasmids, expression and DNA uptake
      were less than for electroporation. Electroporation was also found to transfect
      monolayers with siRNA, which resulted in up to 90% inhibition of targeted protein
      production. Silencing occurred within 24h of transfection and increased with
      increasing siRNA concentration. These results suggest that electroporation can
      provide a valuable research tool for transfection of intestinal epithelial
      monolayers and other differentiated cell systems, and may ultimately be useful
      for clinical gene therapy applications.

PMID- 16564653
TI  - Application of the ion pair concept to the n-octanol-water partitioning of
      cefepime and cefpirome.
AB  - The ion pair concept was applied for the assessment of lipophilicity of cefepime
      and cefpirome. Octanol-water distribution coefficients were determined in
      presence of different concentrations [X-] of sodium octanesulphonate. The log Dx
      values within the linear part of the log Dx/[X-] relationships were extrapolated
      to log Do values corresponding to the partitioning in absence of the counter ion.
      Measurements were feasible at pH values close to the isoelectric points of the
      acidic and basic functions. In that pH range the conduction of the experiments in
      presence of the hydrophobic counter anion facilitated the partitioning of the two
      cephalosporins to octanol, circumventing the problems arising from their high
      hydrophilicity. This procedure could not be applied at lower pH, possibly due to
      a further drastic decrease in the 'intrinsic' lipophilicity or to reduced ion
      pairing potential of octanesulphonate, and at higher pH due to the disruption of
      the zwitterionic structure. Extrapolated log Do values were compared to actual
      log D measurements performed for a reference quinolinium compound and for
      cefpirome. Extrapolated retention factors log kw close to the isoelectric point
      were also determined by reversed phase HPLC and compared to the log Do values.

PMID- 16564654
TI  - A folate receptor-targeted liposomal formulation for paclitaxel.
AB  - A novel liposomal formulation of paclitaxel targeting the folate receptor (FR)
      was synthesized and characterized. This formulation was designed to overcome
      vehicle toxicity associated with the traditional Cremophor EL-based formulation
      and to provide the added advantages of prolonged systemic circulation time and
      selective targeting of the FR, which is frequently overexpressed on epithelial
      cancer cells. The formulation had the composition of dipalmitoyl
      phosphatidylcholine/dimyristoyl phosphatidylglycerol/monomethoxy-polyethylene
      glycol (PEG)2000-distearoyl phosphatidylethanolamine/folate-PEG3350-distearoyl
      phosphatidylethanolamine (DPPC/DMPG/mPEG-DSPE/folate-PEG-DSPE) at molar ratios of
      (85.5:9.5:4.5:0.5) and a drug-to-lipid molar ratio of 1:33. The liposomes were
      prepared by polycarbonate membrane extrusion. The mean particle size of the
      liposomes was 97.1 nm and remained stable for at least 72 h at 4 degrees C. FR
      targeted liposomes of the same lipid composition entrapping calcein were shown to
      be efficiently taken up by KB oral carcinoma cells, which are highly FR+. FR
      targeted liposomes containing paclitaxel showed 3.8-fold greater cytotoxicity
      compared to non-targeted control liposomes in KB cells. Plasma clearance profiles
      of paclitaxel in the liposomal formulations were then compared to paclitaxel in
      Cremophor EL formulation. The liposomal formulations showed much longer terminal
      half-lives (12.33 and 14.23 h for FR-targeted and non-targeted liposomes,
      respectively) than paclitaxel in Cremophor EL (1.78 h). In conclusion, the
      paclitaxel formulation described in this study has substantial stability and
      favorable pharmacokinetic properties. The FR-targeted paclitaxel formulation is
      potentially useful for treatment of FR+ tumors and warrants further
      investigation.

PMID- 16564655
TI  - Pre-deliver chitosanase to cells: a novel strategy to improve gene expression by
      endocellular degradation-induced vector unpacking.
AB  - A radio-labeled plasmid pTracer/Bsd/LacZ containing LacZ reporter gene was
      complexed with different molecular weights of chitosans (CS). Mouse myoblast cell
      line C2C12 was transfected by these chitosan-plasmid DNA complexes, and
      lipofectamine 2000 was used as control. Forty-eight hours after transfection, the
      activity of beta-galactosidase and radioactive count of cell lysis were
      determined. It was found that chitosan, especially low molecular weight species,
      had a surprising ability to deliver DNA into cells, since the radioactive count
      of cells transfected by chitosan-DNA complexes was even two times that of cells
      transfected by lipofectamine 2000. But the beta-galactosidase activity of
      chitosan/DNA complexes was much lower compared to that of lipofectamine 2000.
      Chitosanase which could degrade chitosan in specific mode was transported into
      C2C12 cells by osmotic lysis prior to gene delivery. Then these chitosanase
      modified cells were transfected by CS-DNA complexes. The results indicated that
      beta-galactosidase activity in these cells increased markedly to 425.4 +/- 45.1
      U/mg protein, nearly two-fold as that of cells transfected by liposome. This
      transfection protocol was also applied to 3T3 mouse fibroblast, 2T3 mouse
      osteoblast and MG63 human osteosarcoma cell lines, and an increased gene
      expression level was observed without exception. It is thought that the
      incorporated chitosanase could aid in chitosan degradation, which would promote
      gene unpacking, consequently increasing gene expression.

PMID- 16564656
TI  - Dehydration behavior and structural characterization of the GW275919X
      monohydrate.
AB  - GW275919X, a central muscle relaxant for the treatment of lower back pain, exists
      in a monohydrate. Knowledge of the solid state dehydration behavior and the
      crystal structure is essential for determining its relative physical stability.
      Thermal analysis and hot-stage powder X-ray diffraction were used to study the
      solid state phase transformation during the dehydration process. Crystal
      structure was determined by single crystal X-ray analysis. Molecular modeling
      with Cerius(2) software was used to visualize the hydrate crystal structure and
      to construct the molecular packing and hydrogen bond diagram. Morphology
      prediction was performed using the BFDH calculation. Crystallographic data:
      monoclinic, space group, P21/c, a (Angstrom)=14.3734, b (Angstrom)=5.0336, c
      (Angstrom)=15.4633 and beta=105.11 degrees. Water molecules in the hydrate
      crystal of GW275919X are involved in the hydrogen bonds and these hydrogen bonds
      contribute to the coherence of the crystal structure. The longest dimension of
      the predicted morphology is in the b-direction, which would correspond to the
      needle axis of the experimental crystals.

PMID- 16564657
TI  - Antinociceptive effect of Croton celtidifolius Baill (Euphorbiaceae).
AB  - Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic forest
      of southern Brazil. This plant is used in folk medicine for the treatment of
      several inflammatory diseases, leukaemia, ulcers and other pathologies. Previous
      studies demonstrated anti-inflammatory and antioxidant activities and the
      objective of this work was to investigate a possible antinociceptive action of
      ethanolic extract of Croton celtidifolius bark (EE) and ethyl acetate fraction
      (EAF), n-butanol fraction (FBuOH), and aqueous fraction (FAq) obtained from EE.
      Two standard rodent models of pain were employed for this investigation, the
      writhing test and the formalin test. In the writhing test, the pre-treatment with
      EE significantly reduced the writhing induced by 0.6% acetic acid injection and
      its effect persisted for 4 h. In the formalin test, the pre-treatment with EAF
      caused marked and dose-related inhibition of formalin-induced licking in mice in
      the first phase, while pre-treatment with EAF, FBuOH and FAq had a similar effect
      in the second phase, when given by intraperitoneal (i.p.) and orally (p.o.)
      route. However, given by i.p. route, the effect of fractions was about three to
      five-fold more potent in inhibiting licking than when administered by p.o. route.
      EE presented an antinociceptive effect only in the second phase, when given by
      i.p. or p.o. route. The oedema caused by formalin was significantly reduced in
      animals treated i.p. with EAF, FBuOH and FAq. Under the same experimental
      conditions, in animals treated with sub-fractions derived from EAF only the 63
      sub-fraction significantly reduced nociception in both phases and oedema caused
      by formalin. The results obtained suggest that Croton celtidifolius possesses
      antinociceptive properties since the EE, fractions and a sub-fraction
      significantly reduced the writhing induced by acetic acid and the nociception in
      both phases of the formalin test.

PMID- 16564659
TI  - Radiographic evaluation of third molar development in relation to chronological
      age among Turkish children and youth.
AB  - A sharp increase in forensic age estimation of living persons has been observed
      in recent years. However, ethnic populations residing in different countries have
      been insufficiently analyzed. According to 2004 data compiled by the Essen-based
      Turkey Research Center, there are 3.8 million Turkish people living abroad, and
      3.2 million of them reside in European Union countries. Despite the high number
      of Turks living abroad, little is known about third-molar development for
      forensic application in this population. Hence, it was considered worthwhile to
      determine the developmental stages of the third molar in a group of Turkish
      population, to assess chronological age estimation based on the developmental
      stages, and to compare third molar development according to sex, age and
      location. Orthopantomograms of 1134 Turkish patients, ages 4-20 years were
      examined and third-molar developmental stages were evaluated based on Demirjian's
      classifications. Orthopantomograms were scored by two different observers, and
      Wilcoxon matched-pairs signed-ranks test used to test intra- and inter-observer
      reliability revealed a strong agreement between both intra- and inter-observer
      measurements. Linear regression analysis was performed to correlate third-molar
      development and chronological age, and further statistical analysis was performed
      to determine the relation between sex, age and location. Results showed a strong
      linear correlation between age and molar development (males: r(2)=0.57; females:
      r(2)=0.56). Mineralizations of left and right third molars were compared using
      Wilcoxon tests, and no statistical differences were found. No significant
      differences were found in third-molar development between males and females.
      Mandibular third molar crypt formation was observed in 2.4% of patients at age
      seven and maxillary third molar crypt formation was observed in 1.3% of patients
      at age seven. A strong correlation was found between third-molar development and
      chronological age. Among the Turkish population, third molar crypt formation is
      observable at as early as 7 years in both the mandible and maxilla. Agenesis can
      be determined conclusively if no radiolucent bud is present by age 14.

PMID- 16564658
TI  - A study of ethyl glucuronide in post-mortem blood as a marker of ante-mortem
      ingestion of alcohol.
AB  - The possibility of post-mortem production of ethanol makes correct interpretation
      of ethanol detection in forensic autopsy samples difficult. Even though the
      levels of ethanol formed post-mortem are generally low, this may be highly
      relevant in cases where intake of alcohol was forbidden, for instance for pilots,
      professional drivers and countries with low legal alcohol limits for driving.
      Different criteria are used to determine whether a finding of ethanol is of
      exogenous origin, but there is no marker for alcohol ingestion that has been
      studied in detail. In this study, we wanted to evaluate the sensitivity and
      specificity of ethyl glucuronide (EtG), a direct minor metabolite of ethanol,
      measured in blood, as a marker of ante-mortem alcohol ingestion. Forensic autopsy
      cases were divided into groups with and without ante-mortem alcohol ingestion,
      according to strict inclusion criteria. In 93 cases with information on ante
      mortem alcohol ingestion, EtG was detected in blood in all cases, even when
      levels of ethanol were low. In another 53 cases where there were no indications
      of ante-mortem alcohol intake, EtG could not be detected in blood in a single
      case, also in 11 cases in which ethanol was detected and considered to be most
      probably formed post-mortem. In conclusion, blood EtG determination seems to be a
      reliable marker of ante-mortem ingestion of alcohol, and it could be considered
      in forensic autopsy cases when post-mortem formation of ethanol is questioned.

PMID- 16564660
TI  - Isolated Dandy-Walker malformation associated with brain stem dysgenesis in male
      sibs.
AB  - We describe two brothers with isolated Dandy-Walker malformation (DWM).
      Interestingly, brain stem dysgenesis and abnormal gyral pattern were also
      observed in the sibs. They presented with psychomotor retardation and
      macrocrania. Both suffered from hypotonia with brisk deep tendon reflexes and
      ataxic gait. They had bilateral optic atrophy and the visual evoked potentials
      documented prolonged latencies. Further, motor and sensory conduction velocities
      were normal. Chromosomal examinations for the sibs and their parents showed
      normal results. The majority of cases are sporadic but rare reports of recurrence
      in siblings exist. The parents' consanguinity and the recurrence in a subsequent
      pregnancy suggest an autosomal recessive inheritance pattern. Our report adds
      more weight that brain stem dysgenesis could be associated with DWM, increasing
      the spectrum of heterogeneity of this malformation.

PMID- 16564661
TI  - Successful treatment of a 2-year-old girl with intractable myasthenia gravis
      using tacrolimus.
AB  - We used tacrolimus to successfully treat a patient with childhood-onset
      oropharyngeal myasthenia gravis (MG). A girl (2 years, 5 months old) with
      oropharyngeal MG responded partially to treatment including pyridostigmine
      bromide, intravenous immunoglobulin, and prednisolone (2 mg/kg/day) for 7 weeks,
      but this resulted in worsening of her eye symptoms. By contrast, tacrolimus at 2
      mg/day resulted in complete remission of the MG, which made it possible to reduce
      the dose of prednisolone. This is a rare report of the use of tacrolimus as an
      effective treatment for patients with intractable childhood-onset MG.

PMID- 16564662
TI  - Alzheimer's disease and post-operative cognitive dysfunction.
AB  - Alzheimer's disease (AD), an insidious and progressive neurodegenerative disorder
      accounting for the vast majority of dementia, is characterized by global
      cognitive decline and the robust accumulation of amyloid deposits and
      neurofibrillary tangles in the brain. This review article is based on the
      currently published literature regarding molecular studies of AD and the
      potential involvement of AD neuropathogenesis in post-operative cognitive
      dysfunction (POCD). Genetic evidence, confirmed by neuropathological and
      biochemical studies, indicates that excessive beta-amyloid protein (Abeta)
      generated from amyloidogenic processing of the beta-amyloid precursor protein
      (APP) plays a fundamental role in the AD neuropathogenesis. Abeta is produced
      from APP by beta-secretase, and then gamma-secretase complex, consisting of
      presenilins, nicastrin (NCSTN), APH-1 and PEN-2. Additionally, Abeta clearance
      and APP adaptor proteins can contribute to AD neuropathogenesis via affecting
      Abeta levels. Finally, cellular apoptosis may also be involved in AD
      neuropathogenesis. Surgery and anesthesia can cause cognitive disorders,
      especially in elderly patients. Even the molecular mechanisms underlying these
      disorders are largely unknown; several perioperative factors such as hypoxia,
      hypocapnia and anesthetics may be associated with AD and render POCD via trigging
      AD neuropathogenesis. More studies to assess the potential relationship between
      anesthesia/surgery and AD dementia are, therefore, urgently needed.

PMID- 16564663
TI  - Involvement of UCP3 in mild uncoupling and lipotoxicity.
AB  - Although vital to life, mitochondria are also the major source of ROS production,
      which may have unwanted detrimental effects on DNA, RNA and protein structures
      Therefore, mitochondria must exhibit well-developed mechanisms to regulate its
      ROS production. One such mechanism might be mild uncoupling of the mitochondrial
      respiratory chain, thereby lowering the proton gradient across the inner
      mitochondrial membrane and directly lowering ROS production. Mitochondrial
      uncoupling proteins have been shown to possess mild uncoupling activity and may
      therefore be important regulator of mitochondrial ROS production. The skeletal
      muscle isoform of the uncoupling protein family, UCP3, seems to be specifically
      active under conditions of high fatty acid availability. Although the exact
      function of UCP3 is not yet unravelled, UCP3 is activated by lipid peroxides and
      suggested to export fatty acid anions and/or peroxides from the mitochondrial
      matrix, thereby specifically protecting fatty acids from ROS-induced oxidative
      damage. Protein levels of UCP3 are reduced with aging and in the (pre)-diabetic
      state, both conditions characterized by increased levels of oxidative damage to
      lipids and proteins and reduced mitochondrial function. Whether UCP3 is causally
      related to mitochondrial dysfunction and is essential in the prevention and
      treatment of lipid-induced mitochondrial dysfunction requires further study.

PMID- 16564664
TI  - Caloric restriction and mitochondrial function in the ageing myocardium.
AB  - Extension of life span by caloric restriction is assumed to result from
      retardation of a genetically determined program of ageing, but the new concept of
      hormesis regards caloric restriction as mild stress, which triggers active,
      protective reactions with reparative capacities. Here, we discuss two potential
      hormetic reactions with protective efficacy against dysfunctional mitochondria:
      restoration of neuregulin signalling by upregulation of erbB receptors and
      enhanced biogenesis of functionally active mitochondria by an eNOS-dependent
      mechanism. Mitochondrial ageing is considered to result from a vicious cycle of
      mitochondrial ROS-formation, ROS-mediated damage of mitochondrial DNA,
      disproportional respiratory chain composition and thereby additionally enhanced
      ROS production leading to apoptotic cell loss. Proof-of- principle for such a
      cycle was obtained from transgenic mice with impaired mitochondrial DNA repair
      capacity. Indirect arguments suggest this cycle operating also in ageing wild
      type mammals, accelerated by downregulation of mitochondrial gene expression in
      insulin resistance, by inflammatory excess NO formation, and by downregulation of
      erbB receptors in cardiac ageing and failure. Attenuated neuregulin signalling
      induces a shift in the splice products of the Bcl-x gene from the antiapoptotic
      Bcl-xL protein towards the proapoptotic Bcl-xS protein, resulting in
      mitochondrial dysfunction and apoptosis in cardiomyocytes. Transient caloric
      restriction upregulates erbB receptors and restores mitochondrial Bcl-x-isoform
      patterns and mitochondrial dysfunction in the ageing heart.

PMID- 16564665
TI  - Multi-slice computer tomography of left ventricular function with automated
      analysis software in comparison with conventional ventriculography.
AB  - PURPOSE: To evaluate the accuracy of left ventricular volumetric and functional
      parameters from multi-slice computed tomography using automated analysis
      software, and to correlate results with those of invasive left ventriculography.
      MATERIALS AND METHODS: In 145 consecutive patients (mean age, 61 years+/-12)
      known or suspected to have coronary artery disease, a 16-channel multi-slice
      computed tomography (Philips Mx8000 IDT 16) was performed using a standard
      technique. Using short-axis secondary multi-slice computed tomography
      reformations, we determined end-diastolic and end-systolic left ventricular
      volumes and ejection fraction with a commercially available analysis software
      capable of automated contour detection. Conventional left ventriculography was
      performed according to standard techniques within the following 24 h. Bland
      Altman analysis was performed to calculate the limits of agreement and systematic
      errors between multi-slice computed tomography and conventional left
      ventriculography. RESULTS: As determined by computer tomography, mean end
      systolic (53+/-29 mL) left ventricular volumes had an acceptable correlation with
      conventional ventriculography (67+/-50 mL; r=0.74; p<0.001) and mean end
      diastolic (119+/-33 mL) left ventricular volumes a poor correlation with
      conventional ventriculography measurements (154+/-69 mL; r=0.41). Left
      ventricular ejection fraction (57%+/-14 versus 55%+/-14 for conventional
      ventriculography; r=0.79) showed a very good correlation (p<0.001). Bland-Altman
      analysis showed acceptable limits of agreement (+/-9.2% for ejection fraction)
      without systematic errors. CONCLUSION: The use of a multi-slice computed
      tomography with an automatic calculation software has a good correlation with
      conventional ventriculography findings and could accurately assess left
      ventricular function, but should not be used for ventricular volumes, because of
      biased estimations.

PMID- 16564666
TI  - Altered muscle development and expression of the insulin-like growth factor
      system in growth retarded fetal pigs.
AB  - We have used a porcine model of spontaneous differential fetal growth to
      investigate the effects of fetal size on muscle development. We hypothesized that
      altered muscle development may occur in small fetuses as a consequence of
      modified expression of selected genes of the insulin-like growth factor system.
      We examined the development of the Longissimus muscle (m. Longissimus) in small
      fetuses and their average sized littermates. We collected small for gestational
      age fetuses and their average sized sibling on days 45, 65 and 100 of gestation
      (term is 113-116 days). Small fetuses had significantly lower body weight at all
      three stages of gestation (p<0.05) and significantly reduced secondary to primary
      muscle fibre ratio in m. Longissimus on day 100 (p<0.05) compared to their
      littermates. On day 65, the expression of insulin-like growth factor receptor 1
      and insulin-like growth factor binding protein 3 were significantly higher
      (p<0.05) in m. Longissimus of the small fetuses compared with their average sized
      littermates. On day 100, the expression of insulin-like growth factor receptor 1
      remained significantly higher (p=0.001), in addition to significantly higher
      levels of insulin-like growth factor receptor 2 and insulin-like growth factor
      binding protein 5 in the small fetuses (p<0.05). No difference in levels of
      myogenin was observed between the small and average sized littermates. In
      conclusion, we demonstrate that reduced fetal muscle development is associated
      with an increased expression of several genes of the insulin-like growth factor
      system in small fetuses in mid to late gestation.

PMID- 16564667
TI  - Neuraxial anesthesia in pregnant women with low platelet counts.

PMID- 16564668
TI  - [Request of epidural analgesia by women and obstetrical teams in four French
      areas. Part II: Management of epidural analgesia].
AB  - OBJECTIVE: Epidural analgesia (EA) is widely used in France to treat the labour
      pain. The aim of this study was to evaluate and analyse the rate of EA and the
      ratio between EA required by parturients and total EA realised (performance
      ratio). STUDY DESIGN: An epidemiological survey was sent in all maternity units
      of 4 French areas. Patients and methods. - 48 of the 84 maternity units were
      participating to the study. In each centre, 25 patients fulfilled the
      questionnaire and the medical team fulfilled a questionnaire about the
      organisation of the ward. Rate of EA and performance ratio were calculated.
      Student t test, chi2 test and logistic regression model were used as requested;
      p<0.05 was considered as significant. RESULTS: The mean rate of epidural
      analgesia (EA) rate, in the French areas studied, was 61.6%. It was significantly
      higher in university (79+/-13.7%) and private hospital (73.1+/-20.4%) than in
      general hospitals (54.6+/-19.6%, p<0.01), and also in those where
      anaesthesiologists are dedicated to the maternity unit (71.3+/-17.8 vs 54.6+/
      22.1%, p<0.01) and in hospitals where anaesthesiologists were on duty in the
      hospital versus on call at home (69.8+/-21.4 vs 56.1+/-19%, p<0.02). Median
      duration of EA was 180 minutes, and 21.3% of them lasted more than five hours.
      Most of EA was performed between 8 AM and 6 PM. Patients' request was the major
      reason of EA insertion (OR=11.81), then the midwife request (OR=9.01). Other
      significant factors were the type of the hospital, the anaesthesiologist on duty
      and parity of women. The ratio between the number of EA requested by parturients
      and the total number of EA performed was significantly better in university
      hospitals (100.3+/-13%) and private hospitals (92.2+/-15.7%) than in general
      hospitals (79.4+/-17.3%, p<0.02). For the patients who had requested EA and did
      not have EA, the main reason was that labour was too fast (122/167) and then that
      there was a fail in anaesthesiological organization (59/167). The
      contraindications were rare (14/167). CONCLUSION: To correctly answer to the
      request of EA, it seems necessary that one or more anaesthesiologists were
      dedicated to the maternity units, and that they were on duty into the hospital.
      So it seems important to have large maternities with adequate number of
      anaesthesiologists.

PMID- 16564669
TI  - [Two exciting years].

PMID- 16564670
TI  - Processing speed interacts with working memory efficiency in multiple sclerosis.
AB  - Information processing speed was assessed using the visual threshold serial
      addition test (VT-SAT), a computerized modification of the PASAT designed to
      assess processing speed by controlling for performance accuracy. Persons with MS
      (N=43) and healthy individuals (N=32) were administered the VT-SAT varying
      working memory loads (1-back versus 2-back). Results indicated that at the lower
      working memory load (1-back) all individuals with MS were able to achieve a
      working memory performance level equivalent to healthy individuals, but required
      significantly more processing time to do so. In contrast, at the higher working
      memory load (2-back), about 70% of MS participants were able to achieve a
      performance level equivalent to healthy individuals, but again required
      significantly more processing time. The results are discussed in the context of
      the dynamic nature of the relationship between processing speed and working
      memory performance, emphasizing the dependence of this relationship on other
      cognitive and disease-related factors.

PMID- 16564671
TI  - Do we have a knowledge transfer and translation plan at Teratogen Information
      Services?
AB  - Recently, a new field in science is emerging, which addresses the issue of
      ensuring that information that is generated from research, reaches the right
      people in the right format. This has been coined as knowledge transfer and
      translation and public health leaders worldwide are finding out ways to carry
      this out effectively. Ultimately, this should ensure greater investment in
      knowledge syntheses and transfer initiatives, that involve potential users of
      research to improve the quality of health for everyone. In this brief
      review/comment, an attempt will be made to help the readers understand the
      meaning of this new terminology and how it impacts Teratogen Information
      Services.

PMID- 16564672
TI  - Laboratory assessment and diagnosis of congenital viral infections: Rubella,
      cytomegalovirus (CMV), varicella-zoster virus (VZV), herpes simplex virus (HSV),
      parvovirus B19 and human immunodeficiency virus (HIV).
AB  - Viral infections during pregnancy may cause fetal or neonatal damage. Clinical
      intervention, which is required for certain viral infections, relies on
      laboratory tests performed during pregnancy and at the neonatal stage. This
      review describes traditional and advanced laboratory approaches and testing
      methods used for assessment of the six most significant viral infections during
      pregnancy: rubella virus (RV), cytomegalovirus (CMV), varicella-zoster virus
      (VZV), herpes simplex virus (HSV), parvovirus B19 and human immunodeficiency
      virus (HIV). Interpretation of the laboratory tests results according to studies
      published in recent years is discussed.

PMID- 16564673
TI  - Towards the expression of sex hormone receptors in the human vocal fold.
AB  - BACKGROUND: The human larynx is assumed to be a steroid receptor target organ.
      There are only very limited data on the evidence of steroid receptors in the
      vocal folds, although voice alterations due to hormonal influence and treatment
      have been found. GOAL OF THE STUDY: To investigate the expression of estrogen
      alpha, progesterone, and androgen receptors in human vocal folds (vocalis muscle,
      glands, lamina propria, epithelium). METHODS: Immunohistochemically, vocal fold
      cadaver specimens of 15 autopsied patients (6 women, 9 men), which were taken
      approximately 4 to 8 hours postmortem were investigated. Furthermore, one (male)
      vocal fold biopsy obtained intraoperatively during a laryngectomy was tested.
      RESULTS: No specific immunohistochemical staining for the different types of
      steroid hormones investigated could be observed in either the postmortem taken
      biopsies nor the intraoperatively one. However, several unspecific staining
      patterns could be observed. CONCLUSION: The results of this study contradict
      recently published data and question the expression of sex hormone receptors in
      the vocal folds. Main causes of false interpretations of unspecific staining are
      discussed.

PMID- 16564674
TI  - When does a sung tone start?
AB  - Although the consonant is mostly considered as the start of a syllable in
      phonetics and orthography, musicians generally agree that the vowel onset in
      singing should be synchronized with the beat. As a test of this assumption, the
      current investigation analyzes the time interval between vowel onsets and piano
      accompaniment onsets in a set of songs performed by international vocal artists
      and published on commercial CD recordings. The results show that, most commonly,
      the accompanists synchronized their tones with the singers' vowel onsets.
      Nevertheless, examples of lead and lag were found, probably made for expressive
      purposes. The lead and lag varied greatly between songs, being smallest in a song
      performed in a fast tempo and longest in a song performed in a slow tempo.

PMID- 16564676
TI  - Contact telescopy reveals blood vessel alterations of vocal fold mucosa in
      Reinke's edema.
AB  - AIM: To evaluate contact telescopy findings for estimation of blood vessel
      changes in vocal fold mucosa in patients with Reinke's edema. Histological
      features significant for diagnosis of microvascular vocal fold alteration were
      correlated with clinical findings. METHODS: In 80 patients with Reinke's edema,
      laryngoscopy and video-telescopy image analysis of vocal folds were performed.
      Vocal fold mucosa biopsies were histologically analyzed and compared with contact
      telescopy findings. An interesting aspect of vocal fold microcirculation found
      both by contact telescopy imiging and by histological specimens was described.
      RESULTS: Contact telescopy in vivo revealed different forms of pathological blood
      vessel networks with unusual appearance of loops or branching. Some dilated
      varicose vascular channels had very thin walls, and within atypical capillaries,
      partial erythrocyte accumulation was found. Details of blood flow are also
      visible, showing multidirectional and discontinuous blood flow in neighboring
      vessels. CONCLUSION: The noninvasive contact telescope technique is very useful
      as an additional diagnostic tool for defining a condition of a subepithelial
      Reinke's space in a very short period of time. The great advantage of contact
      telescopy is systematic in vivo and in situ observation of microvascular details
      in the vocal folds. The contact technique allows dynamic follow-up of the
      microcirculation in Reinke's edema as well as simultaneous consultation of a
      pathologist in the operating theater.

PMID- 16564675
TI  - The psychosocial consequences of BOTOX injections for spasmodic dysphonia: a
      qualitative study of patients' experiences.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this study is to examine the psychosocial
      consequences of BOTOX (Allergan, Inc. Irvine, CA) treatment for spasmodic
      dysphonia (SD). This article also explores how patients judge the success of
      treatment and make decisions about future treatment based on psychosocial issues
      relevant to them. STUDY DESIGN: This study follows the phenomenological tradition
      of qualitative inquiry in which the objective is to explore the lived experiences
      of a group of persons who share a common phenomenon, in this case receiving BOTOX
      injections for SD. METHODS: Six adults with SD who had been receiving BOTOX
      injections on a long-term basis participated in face-to-face interviews. The
      interviews were recorded, transcribed, and analyzed according to phenomenological
      guidelines to identify consistent themes as well as differences among
      participants' experiences. RESULTS: The results are summarized in three primary
      themes that suggest (1) participants' experiences vary over time based on changes
      in factors such as lifestyle and personal priorities; (2) BOTOX has
      multidimensional psychosocial implications in physical, personal, and social
      domains; and (3) participants individualize their treatment regimens, taking into
      consideration the burden of treatment, scheduling priorities, and other
      strategies to maximize the benefits of BOTOX. CONCLUSIONS: Based on this study,
      suggestions are provided for future research into a psychosocial outcome
      measurement, including longitudinal evaluations that accommodate changing patient
      priorities over time; multidimensional evaluations that incorporate physical,
      personal, and social issues; evaluations that include a measure of the burden of
      treatment; and evaluations that support a shared decision-making model with the
      voice clinicians.

PMID- 16564677
TI  - PITK, a PP1 targeting subunit that modulates the phosphorylation of the
      transcriptional regulator hnRNP K.
AB  - Protein phosphatase-1 (PP1), through interactions with substrate targeting
      subunits, plays critical roles in the regulation of numerous cellular processes.
      Herein, we describe a newly identified regulatory subunit (PITK; Phosphatase
      Interactor Targeting K protein) that specifically targets the catalytic subunit
      of PP1 to nuclear foci to selectively bind and dephosphorylate the
      transcriptional regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K) at
      a regulatory S284 site. Additionally, PITK is phosphorylated in vivo at S1013 and
      S1017, residues that flank or reside within the PP1C-binding motif, and this
      phosphorylation negatively regulates the binding of the phosphatase to PITK. A
      mutant variant, S1013,1017A-PITK, when expressed in intact cells, exhibited an
      increase in native PP1 binding and elicited a more profound dephosphorylation of
      hnRNPK at S284. A global analysis of transcription by Affymetrix microarray
      revealed that the expression of PITK resulted in the altered expression of 47
      genes, including a marked induction of MEK5 (>14-fold, p<0.007). Additionally,
      the effects of PITK and S1013,1017A-PITK on transcription could be modulated by
      the co-expression of hnRNP K. Taken together, our findings provide a putative
      mechanism by which transcriptional activity of hnRNP K can be discretely
      controlled through the regulation of PP1 activity.

PMID- 16564678
TI  - Cognition and behavior in children with benign epilepsy with centrotemporal
      spikes (BECTS).
AB  - Characteristics of cognitive deficits in benign childhood epilepsy with
      centrotemporal spikes (BECTS) remain unclear. The authors screened 200 BECTS
      children presenting for a clinical trial, finding relative weaknesses in fine
      motor control, visual learning, and attention in the presence of overall normal
      intellect, with simple partial seizures associated with more difficulty. Parental
      concerns for psychosomatic and learning problems were noted. Monitoring select
      cognitive and behavioral features in BECTS appears appropriate.

PMID- 16564679
TI  - Three cases of risperidone-induced enuresis.

PMID- 16564680
TI  - Antimicrobial susceptibilities of Pasteurella strains isolated from humans.
AB  - The in vitro susceptibilities of 192 consecutive clinical strains of Pasteurella
      spp. isolated between 1996 and 2003 from soft tissue pus (n = 146), respiratory
      tract specimens (n = 38) and blood (n = 8) were studied by an agar dilution
      method. All isolates were susceptible to minocycline, cefotaxime, ofloxacin,
      ciprofloxacin and levofloxacin. Most strains were susceptible to moxifloxacin,
      amoxicillin, azithromycin and clarithromycin, whereas lower susceptibility rates
      to telithromycin (89.4%) were observed among respiratory tract isolates.

PMID- 16564681
TI  - Influenza is now a preventable disease.
AB  - The world is waiting with apprehension for the predicted pandemic of H5N1 (avian)
      influenza as an increasing number of countries in Asia, Europe and Africa report
      cases of influenza in migrating birds. All is not 'despondency', however.
      Targeted and controlled administration of antiviral drugs, alone or in
      combination, to contacts and cases, together with well tried public health
      measures, should slow down the spread of the infection and allow time for
      vaccines to be developed, thus preventing a worldwide pandemic of the type that
      occurred in 1918.

PMID- 16564682
TI  - [Cowden's disease: a new paediatric observation].
AB  - We report on a paediatric observation of Cowden's disease in a 6-year-old child.
      Familial steroid-resistant nephrotic syndrome was associated to papulous and
      papillomatous lesions of gingiva and oral mucosa, multiple hamartoma of the back
      and of upper limbs, facial dysmorphism and follicular thyroid cancer. Thyroid
      cancer evolved favorably after surgical treatment, radioactive iodine and L
      thyroxin supplementation. Nephrotic syndrome evolved to chronic renal
      insufficiency after 11 years. The early diagnosis of Cowden's disease, or
      multiple hamartoma syndrome, allows a careful monitoring of the patients who are
      facing the risk of cancer transformation, which is the principal complication of
      the condition.

PMID- 16564683
TI  - [Is there any interest to perform ultrasonography in boys with undescended
      testis?].
AB  - OBJECTIVE: To evaluate the accuracy of ultrasonographic examination in boys with
      an undescended testis. MATERIAL AND METHODS: All patients who were referred to
      the paediatric surgeon after detection of an undescended testis were evaluated
      prospectively between November 2001 and November 2004. Among these 377 patients,
      87 were referred with an ultrasonogram previously prescribed by the referring
      primary physician. The results of the ultrasonogram were compared to the results
      of the clinical examination of the paediatric surgeon and, in cases of no
      palpable testis, to the surgical findings. RESULTS: Ultrasonography did not
      detect the retractile testes. Ultrasonography detected 67% of the palpable
      undescended testes. In cases of no palpable testis, the ultrasonographic
      examination missed the abdominal testes and sometimes other structures were
      falsely interpreted as a testis. CONCLUSION: Sonography has no place in the
      diagnosis of undescended testis.

PMID- 16564684
TI  - [About offsprings of mothers with anorexia nervosa: what about clinical practice
      in pediatric settings?].
AB  - The authors first present the methodological issues raised by studies of the
      offspring of mothers with anorexia nervosa. Malnutrition and low weight appear to
      be the main consequences for the baby. Feeding mother/child interactions are more
      likely to be disturbed during later childhood. Emotional or psychological
      consequences are not well yet studied.

PMID- 16564685
TI  - Asthma insights and reality in Turkey (AIRET) study.
AB  - BACKGROUND: Several international surveys have reported low levels of asthma
      control compared to the levels set by the Global Initiative for Asthma
      guidelines. METHODS: In Turkey, 8350 households were surveyed and 400 current
      asthmatics responded a structured questionnaire on symptom severity, activity
      limitations and disease management. RESULTS: Most of the 55 children and 345
      adults were classified as having persistent asthma (72.7% and 88.1%,
      respectively). In adult asthmatics, 31.3% reported current cigarette smoking and
      10.7% being former smokers. Guideline-based asthma control was achieved in only
      1.3% of participants. Three-quarters of children and more than 90% of adults were
      experiencing daytime symptoms. Most of adult patients and children reported an
      unfavorable impact of asthma on their social lives, and only half had ever had a
      lung function test. Daily anti-inflammatory therapy, including inhaled
      corticosteroids, was low in patients with persistent disease. Patients
      underestimated their disease severity and overestimated their level of disease
      control. CONCLUSIONS: The low level of asthma control in this Turkish population,
      together with the underestimation of disease severity and control by the
      patients, high smoking rates and low level of preventive medicine usage indicate
      a need for better implementation of current guidelines and patient education on
      asthma in Turkey.

PMID- 16564686
TI  - Effect of solution pH and ionic strength on the stability of poly(acrylic acid)
      encapsulated multiwalled carbon nanotubes aqueous dispersion and its application
      for NADH sensor.
AB  - The optimal conditions to prepare water-soluble, stable poly(acrylic acid)
      wrapped multiwalled carbon nanotubes (PAA-MWNTs) complex is presented. PAA-MWNTs
      shows high stability within weak acid to weak basic pH condition. The complex
      also shows good endurance to moderate ionic strengths in the buffer solution. The
      PAA-MWNTs complex film-covered electrode demonstrates stable, excellent
      electrocatalytic activity to oxidize NADH, which makes it possible to prepare
      NADH sensor at a low potential of approximately 0.13 V (versus Ag/AgCl) with the
      linear range of 4-100 microM by differential pulse voltammetry.

PMID- 16564687
TI  - Reflections of other minds: how primate social cognition can inform the function
      of mirror neurons.
AB  - Mirror neurons, located in the premotor cortex of macaque monkeys, are activated
      both by the performance and the passive observation of particular goal-directed
      actions. Although this property would seem to make them the ideal neural
      substrate for imitation, the puzzling fact is that monkeys simply do not imitate.
      Indeed, imitation appears to be a uniquely human ability. We are thus left with a
      fascinating question: if not imitation, what are mirror neurons for? Recent
      advances in the study of non-human primate social cognition suggest a surprising
      potential answer.

PMID- 16564688
TI  - The cognitive neuroscience of remote episodic, semantic and spatial memory.
AB  - The processes and mechanisms implicated in retention and retrieval of memories as
      they age is an enduring problem in cognitive neuroscience. Research from lesion
      and functional neuroimaging studies on remote episodic, semantic and spatial
      memory in humans is crucial for evaluating three theories of hippocampal and/or
      medial temporal lobe-neocortical interaction in memory retention and retrieval:
      cognitive map theory, standard consolidation theory and multiple trace theory.
      Each theory makes different predictions regarding first, the severity and extent
      of retrograde amnesia following lesions to some or all of the structures
      mentioned; second, the extent of activation of these structures to retrieval of
      memory across time; and third, the type of memory being retrieved. Each of these
      theories has strengths and weaknesses, and there are various unresolved issues.
      We propose a unified account based on multiple trace theory. This theory states
      that the hippocampus is needed for re-experiencing detailed episodic and spatial
      memories no matter how old they are, and that it contributes to the formation and
      assimilation of semantic memories and schematic spatial maps.

PMID- 16564689
TI  - Clinical applications of newer radionuclide therapies.
AB  - When radio-iodine was first used in the treatment of metastasized thyroid
      carcinoma in 1943, its success in terms of tumour response, quality of life
      improvement and survival was considered a 'miracle', as in those days metastatic
      cancer was generally fatal. Inspired by this, many efforts have been made to
      apply radioisotope therapy to other tumours. Radionuclide therapy uses
      radioactive isotopes labelled with specific targeting agents that aim to deliver
      the irradiation of the isotope to the tumour, while sparing normal tissues. Its
      unique modality allows to systemically target radiosensitive tumours throughout
      the body. Another important principle is its so-called 'cross-fire' action,
      whereby, owing to the larger reach of the radiation in relation to the cell
      diameter, a tumour cell receives lethal hits also from isotopes in the
      neighbourhood that are not directly associated with this cell. The treatment is
      therefore less hampered by inhomogeneous distribution and metabolism than for
      example chemo- or immunotherapy. The European Association of Nuclear Medicine has
      issued guidelines on so-called 'established' therapies (www.eanm.org), i.e.
      hyperthyroidism, thyroid carcinoma, refractory synovitis, bone metastases, mIBG
      therapy, 32P therapy and Lipiodol therapy. Newer therapies include radio-peptide
      therapy, radio-immunotherapy of lymphoma and microsphere therapy for liver
      cancer. The aim of a recently held workshop at the ECCO13 conference 2005 and
      this review is to inform the oncology community about these new developing
      therapies.

PMID- 16564690
TI  - Evaluation of imatinib mesylate effects on glioblastoma aggressiveness with SPECT
      radiotracer 99mTc-(v)-DMSA.
AB  - In vitro and in vivo studies have demonstrated inhibition of glioblastoma growth
      by imatinib mesylate (Gleevec). Imatinib is an inhibitor of the tyrosine kinase
      activities of platelet-derived growth factor receptor (PDGF-r), which is involved
      in glioblastoma aggressiveness. In this study, we have investigated the link
      between 99mTc-(V)-DMSA, an imaging agent used in Single Photon Emission Computed
      Tomography, cellular accumulation and the biological effects of imatinib mediated
      by PDGF-r in a human glioblastoma cell line U87-MG. Cells treated with imatinib
      showed significant decreases in proliferation, invasion, migration and PDGF-rbeta
      expression. 99mTc-(V)-DMSA cellular uptake studies showed that the specific
      action of imatinib on PDGF-r signal pathway, in the human glioblastoma cell line
      U87-MG, could be followed by radioactive tracer. Furthermore, strong correlations
      between cellular 99mTc-(V)-DMSA uptake and the effect of imatinib therapy on U87
      MG proliferation (r=0.896), invasion (r=0.621) and migration (r=0.822) were
      obtained, likewise for 99mTc-(V)-DMSA uptake and PDGF-r expression (r=0.958). Our
      results show that the biological effects of imatinib therapy on tumour cells
      properties are linked to PDGF-r phosphorylation and could be traced with 99mTc
      (V)-DMSA, which also seems to be a potential tracer to evaluate the response to
      imatinib therapy in glioblastoma.

PMID- 16564691
TI  - The application of a 3D-QSAR (autoMEP/PLS) approach as an efficient
      pharmacodynamic-driven filtering method for small-sized virtual library:
      application to a lead optimization of a human A3 adenosine receptor antagonist.
AB  - We have recently reported that the combination of molecular electrostatic
      potential (MEP) surface properties (autocorrelation vectors) with the
      conventional partial least squares (PLS) analysis can be used to produce a robust
      ligand-based 3D structure-activity relationship (autoMEP/PLS) for the prediction
      of the human A3 receptor antagonist activities. Here, we present the application
      of the 3D-QSAR (autoMEP/PLS) approach as an efficient and alternative
      pharmacodynamic filtering method for small-sized virtual library. For this
      purpose, a small-sized combinatorial library (841 compounds) was derived from the
      scaffold of the known human A3 antagonist pyrazolo-triazolo-pyrimidines. The most
      interesting analogues were further prioritized for synthesis and pharmacological
      characterization. Remarkably, we have found that all the newly synthetized
      compounds are correctly predicted as potent human A3 antagonists. In particular,
      two of them are correctly predicted as sub-nanomolar inhibitors of the human A3
      receptor.

PMID- 16564692
TI  - Software studies for germanium detectors data analysis.
AB  - Efficiency calibrations of multiple high-purity germanium (HPGe) detectors are
      being maintained at the National Institute of Standards and Technology (NIST).
      Four generally available software packages for HPGe detector gamma-ray spectrum
      analysis, including the one currently used at NIST, were tested on spectra
      collected from two HPGe detectors at different source-to-detector distances and
      using point sources and ampoules as calibration geometries. The resulting
      efficiency curves were inter-compared.

PMID- 16564693
TI  - Experimental and MC determination of HPGe detector efficiency in the 40-2754 keV
      energy range for measuring point source geometry with the source-to-detector
      distance of 25 cm.
AB  - A precise model of a 40% relative efficiency p-type HPGe detector was created for
      photon detection efficiency calculation using the MCNP code. All detector
      parameters were determined by different experiments. No experimental calibration
      points were used for the modification of detector parameters. The model was
      validated by comparing calculated and experimental full energy peak efficiencies
      in the 40-2754 keV energy range, for point-source geometry with the source-to
      detector distance of 25 cm.

PMID- 16564694
TI  - Leonardo da Vinci's flights of the mind must continue: cardiac architecture and
      the fundamental relation of form and function revisited.
AB  - This overview addresses the remarkable efficiency of the mammalian heart as a
      pump of unique capacity to quickly vary output and ejection velocity and its
      relation to ventricular geometry, fiber architecture, integrity of collagen
      scaffold and microvasculature and appropriate electrical activation. The unique
      functional capacity of the ventricle depends critically on the organization of
      cardiac muscle fibers in layers of counter-wound helices encircling the
      ventricular cavity in a pattern that allows a special twisting motion during
      systole and early diastole, essential to the mechanical efficiency of the normal
      ventricle to eject and suction venous return. The important contribution of
      advances in imaging techniques is reviewed, especially magnetic resonance with
      tagging and tensor analysis to define fiber orientation; these measurements are
      made without the use of implanted devices that can distort structure and even
      impair function. The impact of loss of optimal fiber orientation and geometry of
      the ventricle as a result of diseases that cause heart failure is analyzed, along
      with the possibility of improvement by carefully planned surgical restoration of
      ventricular geometry. The very encouraging results yielded by these therapeutic
      strategies are critically dependent on a clear understanding of the relation of
      structure and function that our analysis attempts to promote. Simultaneously,
      there is full acknowledgment of the unanswered questions that are inevitable but
      equally essential to the continuing search that scientific progress depends on.

PMID- 16564695
TI  - Diastolic dysfunction in stunned myocardium: a state of abnormal excitation
      contraction coupling that is limited by Na+-H+ exchange inhibition.
AB  - OBJECTIVE: The systolic and diastolic effects of myocardial stunning were studied
      to evaluate the contributions of the endocardial and epicardial segments of the
      ventricular myocardial band, and determine if preconditioning by Na+-H+ exchange
      (NHE) inhibition effected post-stunning dysfunction. METHODS: Thirteen Yorkshire
      Duroc pigs (27.3-38.2 kg) underwent 15 min of mid-LAD clamping. Seven had no
      protective measures and six were pretreated with IV Cariporide 5 mg/kg 15 min
      before ischemia. Sonomicrometer crystals evaluated systolic dysfunction (impaired
      regional shortening) and diastolic dysfunction (contraction extending into early
      diastole). RESULTS: Before ischemia, contraction started first on the endocardial
      side followed 82+/-23 ms later by the subepicardium. Endocardial shortening
      stopped first, coinciding with negative dP/dt onset, while epicardial shortening
      phase persisted for 92+/-33 ms more during occurrence of rapid LVP descent and
      development of peak negative dP/dt. Ischemia produced paradoxical bulging of both
      segments. Sixty minutes after ischemia systolic segment shortening recovered 36+/
      24% of baseline values without pretreatment, compared to 75.8+/-15% with
      Cariporide (p<0.05). Global ejection force (maximum dP/dt) fell 32+/-20% in the
      unprotected group, but was maintained by Cariporide pretreatment. Diastolic
      dysfunction always showed continued endocardial contraction into early diastole
      (occupying 38+/-16% of diastole in untreated hearts), whereas Cariporide
      treatment reduced this dysfunction to 5+/-10% (p<0.05). Persistent diastolic
      dysfunction raised left ventricle end diastolic pressure (LVEDP) 4 mmHg in
      untreated hearts, whereas Cariporide returned LVEDP to normal. Less elevation of
      creatine kinase MB (CK-MB) and conjugated dienes followed Cariporide
      pretreatment. CONCLUSIONS: Temporary LAD ischemia alters the normal sequential
      pattern of contraction responsible for ejection and suction by (a) reducing
      systolic contractile force, and (b) prolonging endocardial contraction into early
      diastole to disrupt the normal endocardial-epicardial sequence responsible for
      ventricular suction. NHE inhibition before ischemia limits postischemic systolic
      and diastolic dysfunction by re-establishing the expected shortening sequences
      within the ventricular myocardial band model.

PMID- 16564696
TI  - Left ventricular geometry in normal and post-anterior myocardial infarction
      patients: sphericity index and 'new' conicity index comparisons.
AB  - BACKGROUND: Anterior myocardial infarction leads a sequence of structural changes
      that alter the size and the shape of the left ventricle. Efforts to assess shape
      have been made by global left ventricular (LV) chamber analysis (sphericity
      index, SI) but this analysis does not detect regional shape abnormalities like
      those at the apical level, which precede global ventricular dilatation.
      OBJECTIVE: The present study will introduce a new analysis of regional apical
      changes in 52 normal subjects and in 92 patients with previous anterior
      myocardial infarction. METHODS: All patients had transthoracic echocardiogram and
      multiple views were obtained (long axis, 4CH, 2CH and short axis view). From the
      4CH view the long and the short axes were measured and their ratio was calculated
      (sphericity index). In the same view, the apical axis length was also measured
      and the ratio between apical and short axis length was calculated (apical
      conicity index, ACI). RESULTS: Patients had all the measured parameters
      significantly worse than normal, except the sphericity index which remained
      unchanged. Ventricular length and width increased following anterior MI but the
      ratio between the two measurements did not change. Conversely, apical conicity
      index is significantly different following anterior MI, thereby indicating
      anterior infarction produces a less conical shape. SI and ACI differed when
      correlations were made in the relationship of mitral valve function; SI
      correlates with the degree of mitral regurgitation (MR) and with the distance of
      papillary muscles, conversely ACI shows an inverse correlation with the
      determinants of mitral regurgitation. These observations reflect differences
      between apical versus global dilatation in ischemic cardiomyopathy, so that
      mitral function is better (lower tenting area and lower coaptation height) when
      the apex is markedly dilated in respect to the short axis (high conicity index).
      In contrast, mitral function is impaired (bigger distance between papillary
      muscles and higher degree of mitral regurgitation), when sphericity index is
      high. CONCLUSIONS: Sphericity index fails to detect regional apical shape
      abnormalities. To address this focal change, we introduce a simple new measure
      termed apical conicity index, which is abnormal in patients with myocardial
      infarction, and can be useful to evaluate changes induced by the subsequent
      surgical approach of ventricular re-shaping.

PMID- 16564697
TI  - Right ventricular restoration during pulmonary valve implantation in adults with
      congenital heart disease.
AB  - OBJECTIVE: Pulmonary regurgitation may cause progressive right ventricular
      dilatation and dysfunction in adult patients previously repaired for right
      ventricular outflow tract obstruction (RVOTO), and who require subsequent valve
      implantation for relief of these symptoms. Right ventricular recovery after
      pulmonary valve implantation (PVI) may be closely linked to the functional
      importance of the structural presence of an aneurysm or akinetic segment in the
      RVOT area. To test this concept, the impact of the right ventricular restoration
      with a new surgical ventriculoplasty technique is evaluated following pulmonary
      valve implantation in patients with severe pulmonary regurgitation and right
      ventricular dilatation. METHODS: Sixteen patients with severe pulmonary valve
      regurgitation (PVR) and right ventricular dilatation with RVOT aneurysm underwent
      right ventricular remodelling since January 2002. Each underwent preoperative
      evaluation by Doppler echocardiography, magnetic resonance imaging (MRI), and
      right ventricular myocardial acceleration during isovolumic contraction (IVC).
      The surgical procedure included pulmonary valve implantation and RVOT restoration
      achieved by removal of the aneurysm tissue, coupled with a ventriculoplasty to
      reduce volume, accomplished by creating a satisfactory RVOT dimension by placing
      with 2-0 Gortex suture to allow acceptance of a 26 Hegar dilator to avoid
      restriction. Thirteen associate surgical procedures were added in nine patients.
      RESULTS: All patients survived the operative procedure and underwent a 16-month
      follow-up interval. A reduction of cardio thoracic index and a clinical
      improvement occurred in each patient. Significant reduction of RVEDV and RVESV
      and increased right ventricular ejection fraction was observed, and IVC changed
      from 0.7+/-0.5 m/s2 to 1.3+/-0.6 m/s2 in the 13 patients that underwent MRI and
      IVC during the preoperative control interval and 6 months after the procedure.
      CONCLUSIONS: This preliminary database implies that the right ventricular
      restoration is a simple and effective procedure, and introduces a structural
      component that should be added during pulmonary valve implantation in patients
      with severe right ventricular dilatation and underlying aneurysm or akinesia of
      the right ventricular outflow tract.

PMID- 16564698
TI  - Form versus disease: optimizing geometry during ventricular restoration.
AB  - OBJECTIVE: Dilated cardiomyopathy from many causes results in a change in
      ventricular geometry, whereby the elliptical chamber becomes more spherical. This
      may be the unifying geometric concept of heart failure, with similar alteration
      of spatial configuration in non-ischemic diffuse myocyte disease, ischemic
      cardiomyopathy with and without scar, and in valvular heart disease. METHODS:
      This change in architecture alters fiber direction and diminishes function, and
      has been related to alteration of the apical loop of the helical ventricular
      myocardial band model of cardiac shape. The underlying concept of rebuilding the
      ventricle by ventricular restoration is suggested to be reconstruction of form,
      rather than focusing on only the underlying disease. RESULTS: Examples are shown
      where the Surgical Anterior Ventricular Exclusion (SAVE) or Pacopexy procedure
      has been successfully applied to each of the above-mentioned diseases, and is
      suggested for dilated valvular cardiomyopathy. The interaction between rebuilding
      form and how this procedure restores more normal fiber orientation is discussed,
      and the possibility of a macroscopic/microscopic marriage between surgically
      altering the cardiac scaffold by restoration (macro) and cell biology to improve
      function in a new helical shape is suggested. CONCLUSIONS: The implication of
      these observations is that the surgical objective should become rebuilding
      ventricular form, rather than restricting restoration procedures to only
      addressing the disease.

PMID- 16564699
TI  - Torrent-Guasp's anatomical legacy.

PMID- 16564700
TI  - Rethinking the cardiac helix--a structure/function journey: overview.

PMID- 16564701
TI  - The septal motor of biventricular function.
AB  - This paper describes the anatomic spiral arrangement of the cardiac
      interventricular septum that results in a twisting action that contributes to the
      forceful ejection of blood from both ventricles during systole. Right ventricular
      (RV) dysfunction seen in various clinical settings is discussed with reference to
      the septum and its mechanism of function. The role of the septum in the
      interdependence of ventricular function is described. The structure/function
      relationships of the septum are related to maintenance of its oblique fiber
      orientation and midline configuration; disruption of this spatial relationship is
      the lynchpin of the concept that 'left heart failure begets right heart failure.'
      The importance of recognizing how alterations in septal anatomy affect
      biventricular performance is related to improved understanding of the clinical
      manifestations of septal dysfunction, designing a management scheme, and
      determining how to prevent septal injury.

PMID- 16564702
TI  - Action of intracellular IL-1Ra (Type 1) is independent of the IL-1 intracellular
      signalling pathway.
AB  - The balance between IL-1 and its naturally occurring inhibitor IL-1 receptor
      antagonist (IL-1ra) is critical in determining the inflammatory response. Four
      splice variants of the IL-1ra gene have been identified; one secreted (sIL-1ra)
      and three intracellular (icIL-1ra1-3). The biological roles of the intracellular
      isoforms remain largely unclear. We wished to determine whether icIL-1ra1 had
      intracellular functions regulating IL-1 signalling. Signalling was determined
      using an NF-kappaB reporter assay measuring induction of the IL-8 promoter in
      transfected cells. Over-expression of icIL-1ra1 in HeLa cells had no effect on IL
      1 stimulated IL-8 activity. In contrast over-expression of sIL-ra significantly
      attenuated IL-1 activity. In addition, transfection of icIL-1ra1 in HeLa cells
      did not cause inhibition of IL-8 promoter activity following over-expression of
      the IL-1 signalling components MyD88, IRAK-1, TRAF-6, Ikappakappabeta or RelA.
      This implies that icIL-1ra1 does not act to alter IL-1 mediated intracellular
      signalling in this system. We investigated whether ATP and/or over-expression of
      the P2X7 receptor caused icIL-1ra1 inhibition of IL-1beta mediated IL-8 reporter
      activation, by permitting its release. In HeLa cells, no effect of icIL-1ra1 was
      observed in ATP stimulated and/or P2X7 transfected cells, compared to a
      significant inhibition in sIL-1ra transfected cells. However, in endothelial
      cells stimulated with ATP, the released fraction was effective in attenuating IL
      1beta activation of the IL-8 reporter. These results suggest that icIL-1ra1 does
      not act at an intracellular level to alter IL-1 mediated signalling, and is
      effective in inhibiting IL-1 responses only when released in an ATP-dependent and
      cell type specific manner.

PMID- 16564703
TI  - Increased production of IL-1alpha and TNF-alpha in lipopolysaccharide-stimulated
      blood from obese patients with non-alcoholic fatty liver disease.
AB  - Enhanced pro-inflammatory cytokine production is considered a pathogenic factor
      in non-alcoholic fatty liver disease (NAFLD). Peripheral blood production of
      interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) was
      studied in relation to the severity of histological changes of the liver in obese
      NAFLD patients. Basal levels in serum and production of IL-1alpha and TNF-alpha
      in peripheral blood cell cultures after stimulation with lipopolysaccharide
      (enzyme-linked immunoabsorbent assays) were measured in 11 patients with
      steatosis and 15 with steatohepatitis, who underwent gastrectomy with a gastro
      jejunal anastomosis in roux and Y, and in 9 controls who underwent anti-reflux
      surgery. Production of IL-1alpha and TNF-alpha was 122 and 67% higher in patients
      with steatosis than control values, respectively. In patients with
      steatohepatitis, IL-1alpha production was 300 and 80% higher and that of TNF
      alpha 110 and 26% higher, as compared with controls and steatosis patients,
      respectively. Production of IL-1alpha was positively correlated with that of TNF
      alpha (r=0.78, p<0.0001). IL-1alpha and TNF-alpha production were both positively
      correlated with the degree of steatosis (r=0.68, p<0.001 and r=0.74, p<0.0001)
      and steatohepatitis (r=0.77 and r=0.75, p<0.0001) at liver biopsy, and with the
      homeostasis model assessment index (r=0.73, p<0.0001 and r=0.63, p<0.01),
      respectively. Basal serum IL-1alpha and TNF-alpha levels were comparable in the
      three groups studied. It is concluded that elevated production of IL-1alpha and
      TNF-alpha by in vitro stimulated whole blood cell cultures occurs in NAFLD obese
      patients, which might play a pathophysiological role upon inflammatory leukocyte
      infiltration of the liver.

PMID- 16564704
TI  - Influence of interleukin-2 and interferon-gamma in murine schistosomiasis.
AB  - Schistosoma mansoni-infected mice were administered at the time of parasite
      residency in the lung with recombinant murine interleukin (IL)-2 or interferon
      gamma (IFN-gamma), to evaluate the impact of cytokines in host responses to
      primary schistosomiasis. S. mansoni lung-stage schistosomula did not affect
      plasma lipids levels in BALB/c, while elicited significant (p<0.05) increase in
      free fatty acids (FA) and decrease in cholesterol plasma levels in C57BL/6 and
      CD1 mice, and stimulated expression of mRNA for Th2 cytokines in BALB/c and Th1
      cytokines in C57BL/6 and CD1 mice. Production of specific antibodies was
      negligible in the 3 strains. Interleukin-2 treatment elicited significant
      (p<0.001) decrease in triglycerides (TG) in CD1, and decrease in TG and
      cholesterol plasma levels and down-regulation of TNF-alpha mRNA expression in
      C57BL/6 mice. Induction of type 2 cytokines and/or IFN-gamma mRNA expression did
      not lead to increase in percentage of specific antibody responders in any mouse
      strain. Exogenous IL-2-related reduction in cholesterol plasma levels and TNF
      alpha mRNA expression in C57BL/6 mice was associated with significant (p<0.05)
      decrease in adult worm recovery and egg count. Treatment with IFN-gamma elicited
      significant (p<0.05) free FA plasma levels increase in BALB/c and C57BL/6 and
      decrease in CD1 mice. Expression of type 2 cytokines mRNA was stimulated in
      BALB/c and CD1 mice, yet was not accompanied with increase in humoral responses.
      Exogenous IFN-gamma-related reduction in free FA plasma levels and IFN-gamma mRNA
      response, and up-regulation of TNF-alpha mRNA expression in CD1 mice were
      associated with significant increase in adult worm burden and egg load. The data
      were discussed in an attempt to define host factors predictive of resistance to
      schistosome infection.

PMID- 16564705
TI  - Preparation of alpha-synuclein fibrils for solid-state NMR: expression,
      purification, and incubation of wild-type and mutant forms.
AB  - We report the expression and purification of alpha-synuclein, a protein
      implicated in Parkinson's disease, from isotopically (13C, 15N) labeled bacterial
      growth media, as required for solid-state NMR structural studies. Expression from
      Escherichia coli (BL21(DE3)) was performed with a protocol optimized for time
      efficiency and yield. Chemical lysis, crude purification by ammonium sulfate
      precipitation, and two chromatography steps (hydrophobic interaction and size
      exclusion) yield 30-35 mg/L of growth medium. Purity is confirmed by gel
      electrophoresis and mass spectrometry. Furthermore, we demonstrate reproducible
      fibril growth by control of environmental incubation conditions. Highly resolved
      multidimensional solid-state NMR spectra indicate microscopic order throughout
      the majority of the AS fibril structure. The number of signals and intensities of
      well-resolved residue types (Thr, Ser, Ala, Gly, Val, and Ile) are consistent
      with a single conformation, which is reproducibly prepared by seeding consecutive
      preparations. Variations in the fibril growth rates and structural polymorphisms
      exhibited in the solid-state NMR spectra are minimized by careful control of
      incubation conditions.

PMID- 16564706
TI  - Cloning, expression, purification, and characterization of Vibrio cholerae
      transcriptional activator, HlyU.
AB  - The HlyU from Vibrio cholerae, involved in the transcriptional regulation of
      haemolysin genes, plays an important role in the regulation of virulence gene
      expression. We have cloned, over-expressed and purified HlyU from V. cholerae
      strain O395 in Escherichia coli, as an N-terminal His6-tagged protein. The
      purified protein gave a single band at approximately 16 kDa on SDS-PAGE, while
      the sequence analysis revealed the molecular weight of 15.8 kDa. The molecular
      mass of HlyU, determined in analytical gel-filtration experiments, was
      approximately 15.7 kDa, an indication that V. cholerae HlyU is a monomer. HlyU
      has two cysteine residues (38 and 104); reaction with sulfhydryl reagent resulted
      in one mol of cysteine residue reacting per mol of HlyU, while the protein
      denatured in guanidine hydrochloride (GdnHCl) showed the reactivity of both the
      residues. Circular dichroism (CD) analysis showed HlyU to be predominantly alpha
      helical, while fluorescence experiment showed that the only tryptophan residue
      present in HlyU is solvent exposed. HlyU was found to exhibit a two-state GdnHCl
      induced unfolding [DeltaG(NU)(H2O) approximately 6.2 kcal mol-1] when monitored
      by far-UV CD and intrinsic tryptophan fluorescence.

PMID- 16564707
TI  - Increased sensitivity in mapping task demand in visuospatial processing using
      reaction-time-dependent hemodynamic response predictors in rapid event-related
      fMRI.
AB  - Searching for the neural correlates of visuospatial processing using functional
      magnetic resonance imaging (fMRI) is usually done in an event-related framework
      of cognitive subtraction, applying a paradigm comprising visuospatial cognitive
      components and a corresponding control task. Besides methodological caveats of
      the cognitive subtraction approach, the standard general linear model with fixed
      hemodynamic response predictors bears the risk of being underspecified. It does
      not take into account the variability of the blood oxygen level-dependent signal
      response due to variable task demand and performance on the level of each single
      trial. This underspecification may result in reduced sensitivity regarding the
      identification of task-related brain regions. In a rapid event-related fMRI
      study, we used an extended general linear model including single-trial reaction
      time-dependent hemodynamic response predictors for the analysis of an angle
      discrimination task. In addition to the already known regions in superior and
      inferior parietal lobule, mapping the reaction-time-dependent hemodynamic
      response predictor revealed a more specific network including task demand
      dependent regions not being detectable using the cognitive subtraction method,
      such as bilateral caudate nucleus and insula, right inferior frontal gyrus and
      left precentral gyrus.

PMID- 16564708
TI  - Phylogeny of sharks of the family Triakidae (Carcharhiniformes) and its
      implications for the evolution of carcharhiniform placental viviparity.
AB  - We present a study of inter- and intra-familial relationships of the
      carcharhiniform shark family Triakidae aimed at testing existing hypotheses of
      relationships for this group and at improving understanding of the evolution of
      reproductive traits in elasmobranchs. Our analyses and conclusions are based on
      evidence from DNA sequences of four protein-coding genes (three from the
      mitochondrial genome and a single copy nuclear gene) from eight of the nine
      genera and 20 of the 39 species currently assigned to the Triakidae. The sequence
      data offer strong support for the following previously proposed triakid clades:
      Galeorhinini (Hypogaleus+Galeorhinus); a subset of the Iagini
      (Furgaleus+Hemitriakis but not Iago); and part of the Triakinae (Mustelus,
      Scylliogaleus and part of Triakis). Interestingly, the molecular data provide
      considerable evidence of paraphyly of the genera Triakis and Mustelus. Our
      results suggest that the subgenera Triakis and Cazon of Triakis represent two
      distinct lineages that are only distantly related and that the genus Mustelus as
      currently defined does not constitute a monophyletic assemblage unless S.
      quecketti and some species of Triakis (subgenus Cazon) are included in Mustelus.
      Within our sample of species of Mustelus (including Cazon and Scylliogaleus), the
      sequence data support two well-defined clades that can be diagnosed by mode of
      reproduction (placental vs. aplacental species). The phylogenetic framework
      presented here is used to infer key events in the evolution and loss of placental
      viviparity among carcharhiniform sharks.

PMID- 16564709
TI  - The influence of cryopreservation on changes in diameter and compliance of
      allografts in an animal experimental model.
AB  - OBJECTIVE: The purpose of this study was to analyze the influence of
      cryopreservation on changes in diameter and compliance of allografts. METHODS:
      Sixty aortic allografts implanted in situ in rats were analyzed. The animals were
      divided into four groups that received fresh or cryopreserved isogenic (Lewis to
      Lewis) grafts, or fresh or cryopreserved allogenic (Lewis to DA) grafts,
      respectively. The diameter and compliance of the grafts were then visually
      evaluated with the digital video camera recorder after 15, 30, 60, 90 and 120
      days. RESULTS: Gradual increase in diameter and decrease in compliance in case of
      all allogenic and cryopreserved isogenic grafts were observed. The observed
      changes in cryopreserved grafts were smaller when compared with fresh grafts,
      however, the differences did not reach statistical significance. CONCLUSION: Cryo
      preservation does not protect allografts from stiffening and dilatation.

PMID- 16564710
TI  - Duplex guided balloon angioplasty of failing infrainguinal bypass grafts.
AB  - OBJECTIVE: To assess the results of angioplasty and stent placement under duplex
      guidance for failing grafts. METHODS: Over 22 months, 25 patients (72% males)
      with a mean age of 74+/-10 years presented to our institution with a failing
      infrainguinal bypass. The site of the most significant stenotic lesion was in the
      inflow in four cases, conduit in 18 cases and at the outflow in 11 cases. All
      arterial (20) or graft (13) entry sites cannulations were performed under direct
      duplex visualization. Duplex scanning was the sole imaging modality used to
      manipulate the guide wire and directional catheters from the ipsilateral CFA to a
      site beyond the most distal stenotic lesion. Selection and placement of balloons
      and stents were also guided by duplex. In 11 cases (33%), the contralateral CFA
      was used as the entry site and a standard approach (fluoroscopy and contrast
      material) was employed. Completion duplex exams were obtained in all cases.
      RESULTS: The overall technical success was 97% (32/33 cases). In only one case,
      the outflow stenotic lesion in the plantar artery could not be traversed with the
      guidewire due to extreme tortuosity. Overall local complications rate was 6% (two
      cases). One vein bypass pseudoaneurysm caused by rupture with a cutting balloon
      was repaired by patch angioplasty and one SFA pseudoaneurysm at the puncture site
      required open repair. Overall 30-day survival rate was 100%. Overall 6-month limb
      salvage and primary patency rates were 100 and 69%, respectively. CONCLUSIONS:
      Duplex guided endovascular therapy is an effective modality for the treatment of
      failing infrainguinal arterial bypasses.

PMID- 16564711
TI  - Vascular surgery: independence and identity as a monospecialty in Europe.

PMID- 16564712
TI  - Endografting of the descending thoracic aorta increases ascending aortic input
      impedance and attenuates pressure transmission in dogs.
AB  - OBJECTIVES: Endografting is being used to manage aneurysms, dissections and acute
      traumatic disruptions of the thoracic aorta. The acute effects of such
      interventions on ventricular afterload and on pressure wave transmission
      characteristics are not well known. METHODS: In five dogs, a 55 mm endograft was
      introduced into the descending aorta, just distal to the left subclavian artery,
      with oversizing of 20%. Following formaldehyde induced complete heart block, the
      hearts were paced (30-120bpm). The ascending aortic pressures and flows were
      recorded using Millar micro-tip manometers and ultrasonic flowmeters,
      respectively. Arterial pressures proximal and distal to the stent site were also
      recorded. For each heart rate, parameters of a modified Windkessel (SVR: systemic
      vascular resistance, Z0: characteristic impedance, C: total arterial compliance)
      were estimated. The pulse wave velocity (PWV) and reflection coefficient (Gamma)
      were calculated from the pressure wave transfer functions. RESULTS: The Z0
      (0.25+/-0.05 vs 0.41+/-0.06 mmHg/ml s(-1), P<.05) was increased and C was
      decreased (0.45+/-0.07 vs 0.28+/-0.04 ml/mmHg, P<0.001) following endograft
      placement. SVR tended to increase (P=.06) and ascending aortic Gamma was
      unchanged. The PWV increased (418+/-67 vs 755+/-135 cm/s, P<.05) and the distal
      Gamma decreased (0.09+/-0.10 vs -0.49+/-0.07, P<.05). CONCLUSIONS: Endografting
      in the proximal descending aorta cause unfavorable changes in the ascending
      aortic input impedance and an increase in the PWV through the grafted segment,
      consistent with an increase in the modulus of elasticity. The grafts produce a
      negative Gamma at the distal end, an uncommon occurrence in the systemic
      circulation. Whether this change is of sufficient magnitude to result in post
      graft dilation is unknown.

PMID- 16564713
TI  - Role of the growth arrest-specific gene 6 (gas6) product in thrombus
      stabilization.
AB  - Growth arrest-specific gene 6 (gas6) product enhances the formation of stable
      platelet macroaggregates in response to various agonists. To determine whether
      Gas6 amplifies the response to known platelet agonists through one or more of its
      receptor tyrosine kinases of the Tyro3 family, mice deficient in any one of the
      Gas6 receptors (Gas6-Rs: Tyro3, Axl, or Mer) were submitted to thrombosis
      challenge and their platelet function. The loss of any one of the Gas6-Rs
      protects mice against thromboembolism induced by collagen-epinephrine and stasis
      induced thrombosis. Importantly, these mice do not suffer spontaneous bleeding
      and have a normal bleeding time but a tendency to repetitively re-bleed after
      transient hemostasis. Re-bleeding in mice lacking any one of the Gas6-Rs is not
      due to thrombocytopenia or coagulopathy but to a platelet dysfunction
      characterized by a lack of the second wave of platelet aggregation and an
      impaired clot retraction, at least in part by reducing outside-in
      alpha(IIb)beta(3) signaling and platelet granule secretion. The early release of
      Gas6 by agonists perpetuates platelet activation through its three receptors,
      reinforcing outside-in alpha(IIb)beta(3) signaling by activation of PI3K and Akt
      signaling and stimulation of tyrosine phosphorylation of the beta(3) integrin.
      Furthermore, "trapping" Gas6 prevents pathological thrombosis, which indicates
      that blocking this novel cross-talk between the Gas6-Rs and alpha(IIb)beta(3)
      integrin may constitute a novel target for antithrombotic therapy.

PMID- 16564714
TI  - Cytosolic calcium concentration is reduced by photolysis of a nitrosyl ruthenium
      complex in vascular smooth muscle cells.
AB  - The effect of the NO donors cis-[RuCl(bpy)(2)(NO)](PF(6)) (RUNOCL) and sodium
      nitroprusside (SNP) on the cytosolic Ca(2+) concentration ([Ca(2+)](c)) was
      studied in cells isolated from the rat aorta smooth muscle of cells isolated from
      the rat aorta smooth muscle. SNP is a metal nitrosyl complex made up of iron,
      cyanide groups, and a nitro moiety; the RUNOCL complex is made up of ruthenium
      and bipyridine ligands, with chloride and nitrosyl groups in the ruthenium axial
      positions. Rat aorta smooth muscle cells were loaded with fluo-3 acetoxymethyl
      ester (Fluo-3 AM) and imaged by a confocal scanning laser microscope excited with
      the 488 nm line of the argon ion laser. Fluorescence emission was measured at 510
      nm. One of the NO donors, RUNOCL (100 micromol/L) or SNP (100 micromol/L), was
      then added to the cell chamber and the fluorescent intensity percentage (%IF) was
      measured after 240 s. RUNOCL reduced the %IF to 60.0+/-10.0% of the initial
      value. After treatment with the soluble guanylyl cyclase inhibitor 1H
      [1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (10 micromol/L), the measurement
      of %IF was 81.0+/-5.0% (n=4). In the presence of tetraethylammonium (TEA) (1
      mmol/L) the %IF was 79.0+/-6.4% (n=4). A combination of ODQ and TEA increased the
      %IF to 97.0+/-3.5% (n=4). As for SNP, it reduced the %IF to 81.4+/-4.7% (n=4),
      but this effect was inhibited by ODQ (%IF 94.0+/-3.6%; n=4) and TEA (%IF 88.0+/
      2.1%; n=4). The combination of ODQ and TEA increased (%IF 92.0+/-2.8%; n=4).
      Taken together, these results indicate that both the new NO donor RUNOCL and SNP
      reduce [Ca(2+)](c). Our data also give evidence that soluble guanylyl cyclase and
      K(+) channels sensitive to TEA are involved in the mechanisms responsible for the
      reduction in [Ca(2+)](c) of the rat aorta smooth muscle cells.

PMID- 16564716
TI  - Evolutionary genetics of juvenile hormone and ecdysteroid regulation in Gryllus:
      a case study in the microevolution of endocrine regulation.
AB  - During the past 15 years the first detailed synthesis of endocrinology and
      population genetics has begun, in which natural genetic variations for endocrine
      regulators have been characterized, almost exclusively in species of the cricket
      genus Gryllus. Artificial selection studies have documented that regulators of
      the juvenile hormone titer can rapidly evolve and exhibit levels of genetic
      variability similar to other physiological traits. Strong genetic correlations
      exist between some but not all regulators of the JH titer during the juvenile
      stage. No genetic correlation exists between regulators functioning in juvenile
      and adult stages, and thus, endocrine regulation can evolve independently in
      these stages. Genetic variation in the JH titer, the ecdysteroid titer, and JHE
      activity, in adult and juvenile stages, have been documented in genetic stocks of
      wing-polymorphic crickets; morph-specific differences in these endocrine traits
      are potentially responsible for genetically based differences in aspects of wing
      and flight muscle development, adult egg production, and adult dispersal. An
      unexpected morph-specific, genetic polymorphism for a circadian rhythm for the JH
      titer was observed in both the laboratory and field. Few comparable studies exist
      in non-Gryllus species, in which in vivo endocrine-genetic variation has been
      directly quantified using reliable analytical methods; many reported cases of
      endocrine variation in these species have been obtained using an inappropriate
      method and thus should be considered unsubstantiated. Obtaining basic information
      on the characteristics of natural genetic variation for endocrine regulators
      still remains one of the most important tasks of the fledgling subdiscipline of
      evolutionary endocrinology. Single gene endocrine mutants in Drosophila are
      promising candidates for investigating molecular-genetic variation in natural
      populations. Future studies should also focus on endocrine traits studied in the
      field and geographic variation in endocrine regulation.

PMID- 16564715
TI  - Thiourea-induced thyroid hormone depletion impairs testicular recrudescence in
      the air-breathing catfish, Clarias gariepinus.
AB  - We used thiourea-induced thyroid hormone depletion as a strategy to understand
      the influence of thyroid hormones on testicular recrudescence of the air
      breathing catfish, Clarias gariepinus. Treatment with 0.03% thiourea via
      immersion for 21 days induced hypothyroidism (thyroid hormone depletion) as
      evidenced by significantly reduced serum T(3) levels. Thiourea-treated males had
      narrowed seminiferous lobules with fewer spermatozoa in testis, very little or no
      secretory fluid, reduced protein and sialic acid levels in seminal vesicles when
      compared to controls. The histological changes were accompanied by reduction in
      serum and tissue levels of testosterone (T) and 11-ketotestosterone (11-KT), a
      potent male specific androgen in fish. Qualitative changes in the localization of
      catfish gonadotropin-releasing hormone (cfGnRH) and luteinizing hormone (LH,
      heterologous system) revealed a reduction in the distribution of immunoreactive
      neuronal cells and fibers in thyroid depleted fish. Interestingly, thiourea
      withdrawal group showed physiological and histological signs of recovery after 21
      days such as reappearance of spermatozoa and partial restoration of 11-KT and T
      levels. These data demonstrate that thyroid hormones play a significant role in
      testicular function of catfish. The mechanism of action includes modulating sex
      steroids either directly or through the hypothalamo (GnRH)-hypophyseal (LH) axis.

PMID- 16564717
TI  - Purification and some properties of two creatine kinase isoforms from herring
      (Clupea harengus) spermatozoa.
AB  - Creatine kinase (CK, EC 2.7.3.2) isoforms play important role in energy
      homeostasis and together with easily diffusible compounds like creatine and
      phosphocreatine maintain a cellular energy buffer and intracellular energy
      transport system. The CK activity in spermatozoa is the highest from all studied
      tissues in herring. It was detected that the two CK isoforms, CK1 and CK2, are
      characteristic only for spermatozoa and are not expressed in other herring
      tissues. Isolation and purification procedures allowed obtaining purified enzymes
      with specific activity of the 345 micromol/min/mg for CK1 and 511 micromol/min/mg
      for CK2. Native Mr's of the CK1 and CK2 determined by gel permeation
      chromatography were about 330,000 and 90,000, respectively. These results
      indicate that CK1 form has octameric structure and CK2 is a dimer mostly
      characteristic for cytosolic CK enzymes. In immunoblotting studies with antisera
      against CK2, the response was observed for CK2 and there was no response for CK1
      and two other isoforms from herring skeletal muscle. These findings make the
      herring isoforms an interesting model for studies on the fish CK biochemical
      properties.

PMID- 16564718
TI  - Invasive non-typhoidal salmonellosis in immunocompetent infants and children.
AB  - OBJECTIVE: To investigate the extraintestinal manifestations of non-typhoidal
      Salmonellae (NTS) infection in immunocompetent infants and children. METHOD: The
      study took place at the University General Hospital at Heraklion, Crete. Over a
      10-year period from 1993-2002 we studied 1087 patients, of whom 443 were children
      less than 14 years old, with a culture-proven diagnosis of NTS infection. Stool
      and blood cultures were routinely obtained in patients presenting with fever and
      diarrhea. The cases of invasive infection in otherwise well children, including
      bacteremia and/or extraintestinal focal infections were further analyzed.
      RESULTS: Invasive cases were less common in children than adults (4.06% vs. 8.7%;
      relative risk 0.467; 95% confidence intervals (CI) 0.279-0.784; p=0.0033).
      Furthermore, invasive cases were much less common in the otherwise well than in
      immunocompromised children (3.5% vs. 21.4%; relative risk 0.163; 95% CI 0.053
      0.500; p=0.0008). The 15 otherwise well children with invasive NTS infection were
      aged from 3 weeks to 7.5 years, and nine were aged less than 12 months. Among
      them, 11 presented with bacteremia, and four with focal extraintestinal
      infections (rectal abscess, deep neck abscess, urinary tract infection, elbow
      arthritis). Salmonella enterica subsp. enterica serovars Enteritidis and Virchow
      were the most common invasive serotypes. All invasive strains were susceptible to
      beta-lactams including ampicillin, and to cotrimoxazole. All patients made a
      complete recovery with intravenous antibiotics and did not present with relapses
      or major infections during long-term follow-up. CONCLUSION: Invasive non
      typhoidal salmonellosis in immunocompetent children is less frequent than in both
      immunocompromised children and in adulthood. However, invasive cases may well
      occur in otherwise healthy children, especially during infancy. In these
      patients, prompt appropriate treatment leads to favorable outcomes.

PMID- 16564719
TI  - Distribution of hepatitis C virus genotypes in the Middle East.
AB  - It is well established that hepatitis C develops into cirrhosis of the liver and
      hepatocellular carcinoma (HCC) both of which are fatal diseases. The World Health
      Organization estimates that there are at least 21.3 million hepatitis C virus
      (HCV) carriers in the Eastern Mediterranean countries, which is close to the
      number of carriers estimated in the Americas and Europe combined. With such a
      high disease burden of HCV infection in this part of the world, and in light of
      the new evidence that genotypes may influence the outcome of antiviral therapy,
      the focus of this review is on the epidemiology and distribution of HCV genotypes
      in the Eastern Mediterranean countries. Accumulated data show that there are two
      main patterns for the distribution of HCV genotypes in the Middle East: in the
      first pattern, genotype 4 is prevalent in most of the Arab countries, and in the
      second pattern, genotype 1a or 1b predominates in the non-Arab countries. Results
      from the limited number of clinical trials on the treatment of chronic HCV
      genotype 4 using peginterferon alfa-2b in combination with ribavirin are
      encouraging. However, efforts to develop more effective antiviral therapies and
      the establishment of an effective HCV vaccine remain the largest challenges for
      the near future.

PMID- 16564720
TI  - Vaccinia immune globulin: current policies, preparedness, and product safety and
      efficacy.
AB  - In 1980 the World Health Organization declared that smallpox was eradicated from
      the world, and routine smallpox vaccination was discontinued. Nevertheless,
      samples of the smallpox virus (variola virus) were retained for research
      purposes, not least because of fears that terrorist groups or rogue states might
      also have kept samples in order to develop a bioweapon. Variola virus represents
      an effective bioweapon because it is associated with high morbidity and mortality
      and is highly contagious. Since September 11, 2001, countries around the world
      have begun to develop policies and preparedness programs to deal with a bioterror
      attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be
      associated with a number of serious adverse events, which can often be managed
      with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in
      patients for whom pre-exposure smallpox vaccine is contraindicated (such as those
      with eczema or pregnant women), although it is currently not licensed in these
      cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have
      been licensed by the FDA for the management of patients with progressive
      vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body
      surface involvement or periocular implantation following inadvertent inoculation.

PMID- 16564721
TI  - Physiological role of the putative ammonium transporter RhCG in the mouse.
AB  - Ammonium excretion into urine is a major process essential to the regulation of
      acid-base homeostasis. We have shown that Rh-type proteins, including renal RhCG,
      belong to the Mep/Amt family of ammonium transporters and promote bi-directional
      ammonium transport upon heterologous expression in yeast. To study the
      physiological role of RhCG and to test a potential function in ammonium
      excretion, we have generated mice bearing an invalidation of the corresponding
      gene.

PMID- 16564722
TI  - Proceedings and abstracts of the International Conference on Rh protein
      superfamily, May 4-5, 2006, Paris, France.

PMID- 16564724
TI  - The challenge of understanding ammonium homeostasis and the role of the Rh
      glycoproteins.
AB  - Rh glycoproteins belong to the superfamily of ammonium transporters, but until
      recent functional studies their functional role was unknown. This review focuses
      on the functional results obtained in our laboratory after the heterologous
      expression of RhAG (the erythroid Rh glycoprotein) and RhCG (an epithelial Rh
      glycoprotein). RhAG and RhCG were expressed in two different expression systems
      (HeLa cells and Xenopus laevis oocytes) that differed in their endogenous
      membrane permeabilities for NH3 and NH4+. To check if RhAG and RhCG are ammonium
      transporters, we measured intracellular pH changes in cells exposed to an
      ammonium-containing solution, and analyzed the ammonium-induced NH3 and NH4+
      transmembrane fluxes in control versus transfected cells. We observed that RhAG
      and RhCG expression induced an enhancement of the ammonium-induced initial
      alkalinization (related to NH3 influx into the cell) and secondary acidification
      (related to NH4+ influx into the cell). Moreover, sub-millimolar ammonium
      concentrations induced inward currents in voltage-clamped RhAG- and in RhCG
      expressing oocytes. Taken together, these results show not only that RhAG and
      RhCG are ammonium transporters, but also that they are promoting the
      transmembrane transport of NH3 and of NH4+. Data from our laboratory and from
      other groups raise several questions that are discussed.

PMID- 16564725
TI  - Target cell CD47 regulates macrophage activation and erythrophagocytosis.
AB  - The ubiquitously expressed cell surface glycoprotein CD47 (integrin-associated
      protein, IAP) was originally identified as a regulator of integrin-dependent
      leukocyte responses to extracellular matrix proteins. However, it has been shown
      that CD47 has several important functions in addition to regulating integrin
      activation. Extensive studies in murine systems have shown that CD47 on
      erythrocytes and other cells can function as a regulator of target cell
      phagocytosis, by binding to the inhibitory receptor SIRPalpha on macrophages. In
      this way, macrophages are less likely to phagocytose an autoimmune sensitized
      cell with CD47 on its surface than a CD47-deficient cell where this inhibitory
      mechanism will not be engaged. The CD47-SIRPalpha interaction seems to be
      important in limiting destruction of host cells in experimental models of
      autoimmune diseases like autoimmune hemolytic anemia (AIHA) or immune
      thrombocytopenia, where macrophages destroy antibody or complement opsonized
      cells.

PMID- 16564723
TI  - Expression of the non-erythroid Rh glycoproteins in mammalian tissues.
AB  - A novel family of proteins, the Mep/AMT/Rh glycoprotein family may mediate
      important roles in transmembrane ammonia transport in a wide variety of single
      celled and multicellular organisms. Results from our laboratory have examined the
      expression of the non-erythroid proteins, Rh B Glycoprotein (Rhbg) and Rh C
      glycoprotein (Rhcg), in a wide variety of mammalian tissues. In the kidney, Rhbg
      and Rhcg are present in distal nephron sites responsible for ammonia secretion.
      In the mouse kidney, Rhbg immunoreactivity is exclusively basolateral and Rhcg
      immunoreactivity is exclusively apical, whereas in the rat kidney Rhcg exhibits
      both apical and basolateral expression. Chronic metabolic acidosis increases Rhcg
      expression in the outer and inner medulla of the rat kidney; these changes, at
      least in the outer medullary collecting duct, involve changes in total cellular
      protein expression in both principal and intercalated cell and changes in its
      subcellular localization. In the liver, Rhbg is present in the basolateral plasma
      membrane of the perivenous hepatocyte and Rhcg is present in bile duct epithelia.
      In the gastrointestinal tract, Rhbg and Rhcg exhibit cell-specific, axially
      heterogeneous, and polarized expression. These patterns of expression are
      consistent with Rhbg and Rhcg mediating important roles in mammalian ammonia
      biology. The lack of the effect of chronic metabolic acidosis on Rhbg expression
      raises the possibility that Rhbg may function either as ammonia sensing-protein
      or that it may mediate roles other than ammonia transport.

PMID- 16564726
TI  - LW protein: a promiscuous integrin receptor activated by adrenergic signaling.
AB  - The LW blood group antigen glycoprotein, although part of the Rh macromolecular
      complex, is nonetheless a member of the intercellular adhesion molecule (ICAM)
      family. Thus, while it is only rarely clinically important in the setting of
      transfusion and pregnancy, LW is likely to contribute to red cell adhesion in a
      variety of settings, including during hematopoiesis, as well as in vascular
      disorders. The best documentation of a pathophysiological role for LW in human
      disease is in sickle cell disease, where it contributes to red cell adhesion to
      endothelial cells and the development of vaso-occlusion, the hallmark of that
      disease. LW may also contribute to other intravascular processes, such as both
      venous and arterial thrombosis, due to its ability to interact with both
      activated platelets as well as leukocytes. The evidence that LW itself can
      undergo activation on red cells holds promise that pharmacotherapeutic maneuvers
      may be found to prevent such pathophysiologic interactions.

PMID- 16564728
TI  - [Biochemical markers of bone remodeling].

PMID- 16564727
TI  - Non-invasive antenatal RHD typing.
AB  - The existence of cell free fetal DNA, derived from apoptotic syncytiotrophoblast,
      in the maternal circulation has opened new possibilities of non-invasive prenatal
      diagnosis. Although still some technical problems exists, especially the lack of
      a generic positive control on the presence of fetal DNA and the aspecific
      amplification of background maternal DNA, non-invasive prenatal RHD typing has
      been successfully introduced in several laboratories, especially in Europe. The
      diagnostic accuracy reaches>99%. In the Netherlands PCR guided administration of
      antenatal anti-D prophylaxis is cost-effective and nearby. In this review the
      main characteristics and applications of cell free fetal DNA are discussed, with
      an emphasis on prenatal RHD genotyping.

PMID- 16564729
TI  - [Minimal ovarian stimulation: certainly less dangerous but rarely as efficient].

PMID- 16564730
TI  - [Clinician and pathologist: a peculiar, yet not dissociable couple].

PMID- 16564731
TI  - [An aborted revolution].

PMID- 16564732
TI  - [Obstetrical forceps: yesterday, today and tomorrow. Toward a new classification
      of obstetric forceps].

PMID- 16564733
TI  - [Insertion problems, removal problems, and contraception failure with Implanon].

PMID- 16564735
TI  - Sexual assault practice: myths and mistakes.
AB  - Stories about sexual activity abound and are often the source of considerable
      interest and speculation. These anecdotal accounts are rarely subjected to any
      serious scrutiny and yet may develop folklore proportions. It is concerning that
      many forensic practitioners are prepared to perpetuate similar myths behind a
      veneer of scientific practice. Practices such as impotence or virginity testing
      and the interpretation of penile measurements are lucrative endeavors that remain
      alive and well. Similarly, court evidence on topics such as the circumstances by
      which genital injuries were sustained, the relationship between pubertal staging
      and age or the interpretation of anal findings are often less than objective.
      These practices are unprofessional. Further, they have the potential to cause
      significant harm to many individuals and to undermine the standing of the
      criminal justice system.

PMID- 16564734
TI  - [Pheochromocytoma and pregnancy. Case report].
AB  - The management of a pheochromocytoma during pregnancy is uncommon and is at high
      risk for both mother and foetus. We report a case of a patient whose first
      pregnancy was complicated by foetal demise in a context suggestive of
      preeclampsia. She was diagnosed with pheochromocytoma as she was beginning a
      second pregnancy. A laparoscopic adrenalectomy was performed in the first
      trimester of pregnancy, and maternal and neonatal outcome were favourable. This
      case illustrates the difficulty of diagnosing pheochromocytoma in pregnancy, and
      the benefits of laparoscopic treatment in the first trimester.

PMID- 16564736
TI  - Sex offenders and confessions: how to overcome their resistance during
      questioning.
AB  - A confession, when properly and fairly obtained, is powerful evidence against a
      suspect and will generally guarantee a conviction. There are a number of
      theoretical models that explain why suspects confess to crimes they have
      committed. In this chapter, the key models and the relevant empirical evidence
      are discussed. The evidence shows that sex offenders, and particularly child
      molesters, sometimes have a strong need to talk about their crimes due to the
      feelings of guilt and this gives the police an advantage. However, sex offenders
      also find it difficult to be open, honest and complete when interrogated due to
      the feelings of shame, which act to inhibit their motivation to confess. They are
      therefore torn between feelings of guilt, which encourages them to confess, and
      feelings of shame, which inhibit them from confessing. As a consequence, feelings
      of shame need to be overcome during the interrogation, which means that sex
      offenders need to be interviewed sensitively and skillfully. Any challenges need
      to be presented in a 'softly' fashion and with understanding of the perpetrator's
      perspective and emotional needs.

PMID- 16564737
TI  - Nurses' and nurse students' demands of functions and usability in a PDA.
AB  - INTRODUCTION: Healthcare organisations are nowadays expecting the support of IT
      in the daily routines. Personal digital assistants (PDAs) are in use in some
      healthcare organisations but in an irregular and unplanned way. The aim of the
      present study was to describe nurses' and nurse students' demands of functions
      and usability in a PDA. METHODS: Interviews were made with 12 nurses at the
      County Hospital of Kalmar and a questionnaire was given to nurse students (n=84)
      in their last, i.e. third, year at the Department of Health and Behavioural
      Sciences, University of Kalmar. RESULTS: There was a need for nurses to make the
      information in general more rich and efficient by means of a PDA. In a PDA, the
      nurses and nurse students expected access to information about the patients,
      knowledge resources and functions for their daily work. CONCLUSIONS: The nurses
      and nurse students had high expectations of a PDA for information retrieval. A
      PDA has the potential to be accepted as a supportive tool in healthcare
      organisations if it contains the demanded content which must be adapted to the
      users' needs and the general IT-system used, and the PDA must have a user
      friendly design.

PMID- 16564738
TI  - Electrophysiological and behavioral evidence of auditory processing deficits in
      children with reading disorder.
AB  - OBJECTIVE: The aim of the research was to investigate auditory processing
      abilities in children with reading disorders using electrophysiological and
      behavioral tasks. METHODS: Differences in auditory processing between control,
      compensated (age appropriate reading skills with a history of reading disorder),
      and reading disordered groups were systematically investigated. RESULTS: The
      reading disorder group had significantly lower results than control and
      compensated reader groups for most tests in the reading and auditory processing
      test battery. All children with a reading disorder did not pass at least one
      behavioral test of auditory processing, and hence would be diagnosed clinically
      as having an auditory processing disorder (APD). The reading disorder group also
      had significantly smaller /ga/-evoked mismatch negativity (MMN) area than the
      control group. Compensated and control groups had similar results for the
      electrophysiological and behavioral auditory processing tests. Correlation
      analyses showed that reading fluency and accuracy and nonword scores (measured
      using Castle and Coltheart's word/nonword test) correlated significantly with
      most APD measures. CONCLUSIONS: The general profile of auditory processing
      deficits in children with reading disorder was a combination of deficits on
      frequency patterns (i.e. frequency pattern test) and absent or small /ga/-evoked
      MMN. Significant results from the correlation analyses support the co-morbidity
      of reading and auditory processing disorders. SIGNIFICANCE: Children with reading
      disorders are likely to have auditory processing disorders.

PMID- 16564739
TI  - Cortical excitability and age-related volumetric MRI changes.
AB  - OBJECTIVE: Normative data on transcranial magnetic stimulation (TMS)-derived
      measures of cortical excitability in the elderly is sparse. Nevertheless, elderly
      subjects are included as controls in studies utilizing TMS to investigate disease
      states. Age-associated increased ventricular cerebrospinal fluid CSF (vCSF) and
      white matter hyperintensity (WMH) MRI volumes have uncertain significance in non
      demented elderly. Information regarding cortical excitability in neurologically
      intact elderly would augment our understanding of the pathophysiology of aging
      and assist in the interpretation of TMS studies involving elderly subjects.
      METHODS: Twenty-four healthy elderly subjects underwent TMS testing to determine
      outcomes of resting motor threshold (RMT) cortical silent period (cSP) and
      central motor conduction time for examination in relation to WMH, vCSF, and CNS
      volumes. RESULTS: Increased vCSF and WMH volumes were associated with decreased
      right and left hemisphere RMT. Smaller CNS volumes were associated with decreased
      right hemisphere RMT and shorted cSP. CONCLUSIONS: Commonly observed age
      associated MRI changes are associated with findings consistent with increased
      cortical excitability. SIGNIFICANCE: Age-related MRI findings likely reflect
      changes at a cellular level, and may influence cognitive and motor integrity in
      the elderly. Future TMS studies investigating cortical excitability may wish to
      consider neuroimaging markers of neurodegeneration prior to enrolling elderly
      subjects as controls.

PMID- 16564740
TI  - Frontal white matter volume and delta EEG sources negatively correlate in awake
      subjects with mild cognitive impairment and Alzheimer's disease.
AB  - OBJECTIVE: A relationship between brain atrophy and delta rhythmicity (1.5-4 Hz)
      has been previously explored in Alzheimer's disease (AD) subjects [Fernandez A,
      Arrazola J, Maestu F, Amo C, Gil-Gregorio P, Wienbruch C, Ortiz T. Correlations
      of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer
      disease: volumetric MR imaging-magnetoencephalographic study. Am J Neuroradiol.
      2003 24(3):481-487]. In this study, we tested the hypothesis that such a
      relationship does exist not only in AD patients but also across the continuum of
      subjects with mild cognitive impairment (MCI) and AD. METHODS: Resting, eyes
      closed EEG data were recorded in 34 MCI and 65 AD subjects. EEG rhythms of
      interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5
      13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were
      estimated by LORETA. Cortical EEG sources were correlated with MR-based
      measurements of lobar brain volume (white and gray matter). RESULTS: A negative
      correlation was observed between the frontal white matter and the amplitude of
      frontal delta sources (2-4 Hz) across MCI and AD subjects. CONCLUSIONS: These
      results confirmed for the first time the hypothesis that the sources of resting
      delta rhythms (2-4 Hz) are correlated with lobar brain volume across MCI and AD
      subjects. SIGNIFICANCE: The present findings support, at least at group level,
      the 'transition hypothesis' of brain structural and functional continuity between
      MCI and AD.

PMID- 16564741
TI  - Periodic limb movement counting in polysomnography: effects of amplitude.
AB  - BACKGROUND AND PURPOSE: This study investigates the relationship between periodic
      limb movement (PLM) counts obtained with standard scoring criteria and PLM counts
      scored without amplitude criterion (AC). PATIENTS AND METHODS: Twenty-four sleep
      laboratory patients with a PLM index (PLMI) >5 per hour of sleep in a previous
      polysomnography (PSG) underwent a full night of digital PSG. PLM were twice
      scored manually: first, according to standard criteria, and second, without AC.
      RESULTS: The overall PLMI for time in bed was 34.4+/-30.7 with AC and 50.2+/-36.4
      without AC. The PLMI in non-rapid eye movement (NREM) sleep was 45.3+/-40.1
      versus 63.4+/-47.6 (P<0.001), in REM sleep 11.5+/-15.1 versus 25.7+/-35.4
      (P=0.001) and in wakefulness 29.0+/-31.1 versus 46.0+/-36.1 (P<0.001) with and
      without AC (Wilcoxon tests). CONCLUSIONS: In comparison to PLM counts obtained
      with standard criteria, PLM counts obtained without consideration of amplitude
      are remarkably higher. Counting without AC increases the sensitivity to detect
      small PLM and probably allows for identification of PLM sequences which would not
      have fulfilled the periodicity criteria otherwise. PLM counts without AC might be
      more useful to investigate the periodicity of PLM and possible changes with
      treatment.

PMID- 16564742
TI  - Sleep habits and risk factors for sleep-disordered breathing in infants and young
      toddlers in Louisville, Kentucky.
AB  - INTRODUCTION: Snoring affects biobehavioral development among preschool and early
      school-age children. The goals of the present study were to survey the parents of
      a large community sample of infants and young toddlers to evaluate (a)
      naturalistic sleep duration and location; (b) snoring prevalence; and (c)
      demographic measures and sleep behaviors related to the presence of snoring
      either 2 or >or=3 days/week. METHODS: Questionnaires were completed by parents of
      children ages 2 weeks to 2 years attending well-baby checkups and were also
      mailed to the homes of six-month-old infants. RESULTS: Data from 944 children
      were available for analyses. No age differences were reported for total sleep
      duration, co-sleeping, or snoring. Average daily sleep duration was 12.5+/-1.8h
      (standard deviation (SD)), with daytime naps accounting for an increased
      proportion of total sleep duration among younger infants. Co-sleeping was
      reported by 15% of families. Snoring 2 days/week was reported in 11.8% and>
      days/week in 5.3% of participants. Survey items indicating risk for sleep
      disordered breathing (SDB) clustered into factors related to the child, their
      environment, and their family; restless sleep was exclusively related to snoring
      2 days/week and ethnicity, sweating during sleep, and noisy breathing exclusive
      to snoring >or=3 days/week. CONCLUSIONS: Young infants appear to sleep less than
      currently recommended. Co-sleeping is relatively common and not age-dependent
      through the first 2 years of life. Items relating to the child's sleep behaviors,
      environment, and parents' perceptions were predictive of positive report of
      snoring, with snoring rates consistent with a significant risk for SDB being
      similar to those reported for older children.

PMID- 16564744
TI  - Circadian rhythms in RLS.

PMID- 16564745
TI  - Mathematical models and lymphatic filariasis control: endpoints and optimal
      interventions.
AB  - The current global initiative to eliminate lymphatic filariasis is a major
      renewed commitment to reduce or eliminate the burden of one of the major helminth
      infections from resource-poor communities of the world. Mathematical models of
      filariasis transmission can serve as an effective tool for guiding the scientific
      development and management of successful community-level intervention programmes
      by acting as analytical frameworks for integrating knowledge regarding parasite
      transmission dynamics with programmatic factors. However, the power of these
      tools for supporting control interventions will be realized fully only if
      researchers address the current uncertainties and gaps in data and knowledge of
      filarial population dynamics and the effectiveness of currently proposed
      filariasis intervention options.

PMID- 16564747
TI  - A protease inhibitor specifically inhibits growth of HPV-infected keratinocytes.
AB  - Protease inhibitors have been known to exhibit anticarcinogenic activity in a
      variety of model systems, although the biological target(s) and mechanism remain
      enigmatic. Human papillomavirus (HPV) is the primary etiological agent of
      cervical cancer. Here we show that a nuclear chymotrypsin-like protease activity
      (NCLPA), which appears to be involved in transformation in several different
      experimental models, is significantly elevated in keratinocytes infected with
      high-risk HPV. Further, we demonstrate a marked growth inhibition of organotypic
      raft cultures, which is specific for cells infected with high-risk HPV types,
      using a chloromethyl ketone inhibitor previously shown to be relatively selective
      for the NCLPA. Surprisingly, this HPV-dependent inhibitory effect is independent
      of any alterations in the NCLPA. This finding has clear implications for the
      development of novel therapeutics specifically targeted to cervical dysplasias
      with HPV-infected cells.

PMID- 16564748
TI  - Beyond the data deluge: data integration and bio-ontologies.
AB  - Biomedical research is increasingly a data-driven science. New technologies
      support the generation of genome-scale data sets of sequences, sequence variants,
      transcripts, and proteins; genetic elements underpinning understanding of
      biomedicine and disease. Information systems designed to manage these data, and
      the functional insights (biological knowledge) that come from the analysis of
      these data, are critical to mining large, heterogeneous data sets for new
      biologically relevant patterns, to generating hypotheses for experimental
      validation, and ultimately, to building models of how biological systems work.
      Bio-ontologies have an essential role in supporting two key approaches to
      effective interpretation of genome-scale data sets: data integration and
      comparative genomics. To date, bio-ontologies such as the Gene Ontology have been
      used primarily in community genome databases as structured controlled
      terminologies and as data aggregators. In this paper we use the Gene Ontology
      (GO) and the Mouse Genome Informatics (MGI) database as use cases to illustrate
      the impact of bio-ontologies on data integration and for comparative genomics.
      Despite the profound impact ontologies are having on the digital categorization
      of biological knowledge, new biomedical research and the expanding and changing
      nature of biological information have limited the development of bio-ontologies
      to support dynamic reasoning for knowledge discovery.

PMID- 16564749
TI  - How to write health dialog for a talking computer.
AB  - Automated dialogue systems delivered over the telephone offer a promising
      approach to delivering health-related interventions to populations of individuals
      at low-cost. Over the past two decades, an automated telephone system called
      Telephone-Linked Care or TLC has been successfully designed and evaluated by the
      authors and their colleagues. This work has resulted in over twenty systems for
      various health-related conditions and lifestyle behaviors. This paper describes
      our approach to developing and writing dialogue for these automated telephone
      systems, including determining the program objectives, defining the target
      population, and selecting a theory of behavior change to guide the intervention.
      Both macro and micro issues are considered in constructing dialogue systems that
      are engaging for the target population, easy to use, and effective at promoting
      positive health behaviors and outcomes.

PMID- 16564750
TI  - Immunosensor interface based on physical and chemical immunoglobulin G adsorption
      onto mixed self-assembled monolayers.
AB  - An immunosensor interface based on mixed hydrophobic self-assembled monolayers
      (SAMs) of methyl and carboxylic acid terminated thiols with covalently attached
      human Immunoglobulin G (hIgG), is investigated. The densely packed and organised
      SAMs were characterised by contact angle measurements and cyclic voltammetry. The
      effect of the non-ionic surfactant, Tween 20, in preventing nonspecific
      adsorption is addressed by ellipsometry during physical and covalent hIgG
      immobilization on pure and mixed SAMs, respectively. It is clearly demonstrated
      that nonspecific adsorption due to hydrophobic interactions of hIgG on methyl
      ended groups is totally inhibited, whereas electrostatic/hydrogen bonding
      interactions with the exposed carboxylic groups prevail in the presence of
      surfactant. Results of ellipsometry and Atomic Force Microscopy, reveal that the
      surface concentration of covalently immobilized hIgG is determined by the ratio
      of COOH / CH(3)-terminated thiols in SAM forming solution. Moreover, the
      ellipsometric data demonstrates that the ratio of bound anti-hIgG / hIgG depends
      on the density of hIgG on the surface and that the highest ratio is close to
      three. We also report the selectivity and high sensitivity achieved by
      chronoamperometry in the detection of adsorbed hIgG and the reaction with its
      antibody.

PMID- 16564752
TI  - Modulation of aerial respiratory behaviour in a pond snail.
AB  - Aerial respiratory in Lymnaea is driven by a three-neuron CPG whose sufficiency
      and necessity has been directly demonstrated. While this CPG is 'hard-wired' it
      displays a tremendous amount of plasticity. That is, it is possible by employing
      specific training procedures to alter how it functions in a specific hypoxic
      environment. Thus, it is possible to study directly the causal mechanisms of long
      term memory formation, forgetting, and modulation of the memory at a single cell
      level. Thus, it is possible to use a relatively simple three-neuron CPG to study
      not only important questions concerning regulation of important homeostatic
      mechanisms but to also use it to study how learning and non-declarative memory
      are mediated at a cellular level.

PMID- 16564751
TI  - A role for Mlh3 in somatic hypermutation.
AB  - Somatic hypermutation (SHM) and class switch recombination (CSR) allow B cells to
      make high affinity antibodies of various isotypes. Both processes are initiated
      by activation-induced cytidine deaminase (AID) to generate dG:dU mismatches in
      the immunoglobulin genes that are resolved differently in SHM and CSR to
      introduce point mutations and recombination, respectively. The MutL homolog MLH3
      has been implicated in meiosis and DNA mismatch repair (MMR). Since it interacts
      with MLH1, which plays a role in SHM and CSR, we examined these processes in Mlh3
      deficient mice. Although deficiencies in other MMR proteins result in defects in
      SHM, Mlh3(-/-) mice exhibited an increased frequency of mutations in their
      immunoglobulin variable regions, compared to wild type littermates. Alterations
      of mutation spectra were observed in the Jh4 flanking region in Mlh3(-/-) mice.
      Nevertheless, Mlh3(-/-) mice were able to switch to IgG3 or IgG1 with similar
      frequencies to control mice. This is the first instance where a loss of a DNA
      repair protein has a positive impact on the rate of SHM, suggesting that Mlh3
      normally inhibits the accumulation of mutations in SHM.

PMID- 16564753
TI  - Hair analysis for veterinary drug monitoring in livestock production.
AB  - This review summarizes the basic information and applications concerning the use
      of hair analysis for the detection of misuse of therapeutic and anabolic agents
      in livestock animals. Hair biology, hair-shaft structure and the mechanisms of
      drug incorporation are described, considering the different factors which can
      affect the deposition. Sampling and extraction methods are reviewed with special
      attention to the particularities of this matrix, while the use of different
      analytical techniques is discussed, taking into account the concentration and the
      sensitivity required for drug detection. Advantages, drawbacks, promising
      prospects and possible applications of this technique in the future are also
      discussed.

PMID- 16564755
TI  - Seasonality in IBD: do we really know about it?

PMID- 16564756
TI  - Fetal-to-neonatal maladaptation.
AB  - Although the majority of newly born babies will establish normal respiratory and
      circulatory function without help, 1-2% might run into difficulties because of a
      disturbance in the normal adaptive processes required for a smooth transition
      from intrauterine to extrauterine life. An understanding of the normal and
      abnormal perinatal physiology is important to appreciate the practical
      differences in the approach to caring for such babies, and also for avoiding
      actions that might be detrimental in the longer term.

PMID- 16564757
TI  - Prader-Willi-like phenotype: investigation of 1p36 deletion in 41 patients with
      delayed psychomotor development, hypotonia, obesity and/or hyperphagia, learning
      disabilities and behavioral problems.
AB  - Monosomy 1p36 is one of the most commonly observed mental retardation (MR)
      syndromes that results in a clinically recognizable phenotype including delayed
      psychomotor development and/or MR, hypotonia, epilepsy, hearing loss, growth
      delay, microcephaly, deep-set eyes, flat nasal bridge and pointed chin. Besides,
      a Prader-Willi syndrome (PWS)-like phenotype has been described in patients with
      1p36 monosomy. Forty-one patients presenting hypotonia, developmental delay,
      obesity and/or hyperphagia and behavioral problems who tested negative for PWS
      were investigated by FISH and/or microsatellite markers. Twenty-six were analyzed
      with a 1p-specific subtelomeric probe, and one terminal deletion was identified.
      Thirty patients (15 of which also studied by FISH) were investigated by
      microsatellite markers, and no interstitial 1p36 deletion was found. Our patient
      presenting the 1p36 deletion did not have the striking features of this monosomy,
      but her clinical and behavioral features were quite similar to those observed in
      patients with PWS, except for the presence of normal sucking at birth. The extent
      of the deletion could be limited to the most terminal 2.5 Mb of 1p36, within the
      chromosomal region 1p36.33-1p36.32, that is smaller than usually seen in monosomy
      1p36 patients. Therefore, chromosome 1p36.33 deletion should be investigated in
      patients with hypotonia, developmental delay, obesity and/or hyperphagia and
      behavioral problems who test negative for PWS.

PMID- 16564758
TI  - Noneosinophilic inflammatory bronchial casts.

PMID- 16564760
TI  - Response to "Science, skepticism, and global warming".

PMID- 16564762
TI  - The serotonin syndrome complicating co-prescription of paroxetine and
      clarithromycin.

PMID- 16564763
TI  - Clinical trials of uric acid lowering for coronary heart disease risk reduction.

PMID- 16564765
TI  - Chekhov's "The Butterfly".

PMID- 16564766
TI  - In medicine, signs of evolution are ever-present.

PMID- 16564767
TI  - Opioid contracts in chronic nonmalignant pain management: objectives and
      uncertainties.
AB  - In this article, we review the principal objectives and ideal elements of opioid
      contracts, as articulated by proponents of the practice. We examine the limited
      empirical evidence for the effectiveness of opioid contracts in achieving their
      intended objectives and identify areas of uncertainty and of ethical concern
      regarding their implementation. We argue that the challenge in deciding about
      implementing opioid contracts in clinical practice relates to the multiplicity of
      potential objectives they might serve, to a lack of empirical evidence regarding
      their effectiveness, and to ethical concerns over their implementation. Specialty
      and primary care clinicians contemplating the use of opioid contracts in treating
      patients with chronic nonmalignant pain need to be sensitive to these
      considerations, and further debate and research is necessary to establish the
      proper objectives, elements, effectiveness, and ethical justifications of opioid
      contracts in clinical practice.

PMID- 16564768
TI  - Hypothermia: evaluation, electrocardiographic manifestations, and management.
AB  - Hypothermia-related cases typically occur after exposure to low ambient
      temperatures; however, numerous cases occur in individuals with no history of
      exposure to cold environment. Hypothermia is associated with such complications
      as acidosis, impaired myocardial function, bleeding diathesis, and decreased
      kidney and liver function. The well-known electrocardiographic manifestations of
      hypothermia are the presence of J (Osborn) waves, prolonged PR, QRS, and QT
      intervals, and atrial arrhythmias. The choice of rewarming therapy is based on
      the degree of hypothermia. The evaluation, electrocardiographic manifestations,
      and management of hypothermia are reviewed.

PMID- 16564769
TI  - Management of the red eye for the primary care physician.
AB  - For the primary care physician, the occurrence of a red eye is a frequent and
      prominent finding of a disease process in patients. A careful history and simple
      examination with the observation of typical clinical signs are important for the
      management of this common disorder. The causes can be classified as painful red
      eye, trauma, and other common conditions. The most frequent causes of a red eye,
      such as dry eye, conjunctivitis, keratitis, iritis, acute glaucoma,
      subconjunctival hematoma, foreign bodies, corneal abrasion, and blunt or
      penetrating trauma, are described in this article. Simple diagnostic methods and
      an emergency management with some useful topical ophthalmic preparations are
      included. Although several conditions can be treated by the primary care
      physician the clinical signs that require an urgent ophthalmic consultation are
      chemical burns, intraocular infections, globe ruptures or perforations, and acute
      glaucoma.

PMID- 16564770
TI  - A dish best served hot.

PMID- 16564772
TI  - Block times two.

PMID- 16564771
TI  - Thwarting a killer.

PMID- 16564773
TI  - Cerebral hypoperfusion can be improved by carotid artery stenting.

PMID- 16564774
TI  - Glucose metabolism in patients with essential hypertension.
AB  - PURPOSE: Arterial hypertension is an insulin-resistant condition that has been
      associated with an increased incidence of diabetes. We assessed the prevalence of
      glucose abnormalities in a population of patients with essential hypertension.
      METHODS: In this cross-sectional study, 420 consecutively referred essential
      hypertensive patients were studied at 16 hypertension clinics in university and
      community hospitals of Spain. Fasting and 2-hour plasma glucose and insulin
      levels were determined in nondiabetic patients. RESULTS: An abnormal glucose
      metabolism was diagnosed in 68.5% (95% confidence interval [CI], 63.7%-72.9%) of
      the patients. Isolated insulin resistance, defined by a homeostasis model
      assessment-estimated insulin resistance (HOMA-IR) equal to or above 3.8, was
      shown in 9.3% (95% CI, 6.7%-12.5%); impaired fasting glucose in 11.2% (95% CI,
      8.6%-14.7%); impaired glucose tolerance in 22.5% (95% CI, 18.5%-26.9%); silent
      undiagnosed type 2 diabetes in 11.5% (95% CI, 8.6%-14.5%); and known diabetes
      mellitus in 13.9% (95% CI, 10.4%-17.2%) of the patients. According to the
      European Group for the Study of Insulin Resistance and the Adult Treatment
      Program III criteria, the metabolic syndrome was diagnosed in 41.5% (95% CI,
      35.9%-47.3%) and 47.9% (95% CI, 43.1%-52.8%) of the patients, respectively. The
      prevalence of left ventricular hypertrophy (defined by a left ventricular mass
      index [LVMI] >125 g/m2 was 44.2%. The relation between HOMA-IR and LVMI was
      statistically nonsignificant, and the LVMI values in the HOMA-IR quartiles were
      similar. Only 27 patients (6.4%) showed good control of cardiovascular risk
      factors. In most patients (273, 65%; 95% CI, 60.3%-69.4%) 2 or more
      cardiovascular risk factors were identified as not being under control.
      CONCLUSIONS: Two thirds of the patients attending hypertension clinics with
      essential hypertension show an abnormal glucose metabolism. The metabolic
      syndrome can be identified in a substantial number of these patients, and 2 or
      more cardiovascular risk factors are not controlled in the majority of patients.

PMID- 16564776
TI  - Cardiocerebral resuscitation improves survival of patients with out-of-hospital
      cardiac arrest.
AB  - PURPOSE: The guidelines for cardiopulmonary resuscitation (CPR) have been in
      place for decades; but despite their international scope and periodic updates,
      there has been little improvement in survival rates in out-of-hospital cardiac
      arrest for patients who did not receive early defibrillation. The Emergency
      Medical Service directors in 2 rural Wisconsin counties initiated a new protocol
      for the pre-hospital management of adult cardiac arrest victims in an attempt to
      improve survival rates. The results observed after implementation of this
      protocol are presented and compared with those observed during a three-year
      period that preceded initiation of the project. METHODS: The protocol, based upon
      the principles of cardiocerebral resuscitation, was significantly different from
      the standard CPR protocol. A major objective was to minimize interruptions of
      chest compressions. Each defibrillation, including the first, was preceded by 200
      uninterrupted chest compressions. Single shocks, rather than stacked shocks, were
      utilized. Post shock rhythm and pulse checks were eliminated, and chest
      compressions were resumed immediately after a shock was delivered. Initial airway
      management was limited to an oral pharyngeal device and supplemental oxygen. If
      the arrest was witnessed, assisted ventilations and intubation were delayed until
      either a return of spontaneous circulation or until three series of "compressions
      + analysis +/- shock" were completed. RESULTS: In the 3 years preceding the
      change in protocol, where standard CPR was utilized, there were 92 witnessed out
      of-hospital adult cardiac arrests with an initially shockable rhythm. Eighteen
      patients survived, and 14 of 92 (15%) were neurologically intact. After
      implementing the new protocol in early 2004, there were 33 witnessed out-of
      hospital adult cardiac arrests with an initially shockable rhythm. Nineteen
      survived, and 16 of 33 (48%) were neurologically normal. Differences in both
      total and neurologically normal survival are significant (chi-squared = 0.001).
      CONCLUSION: Instituting the new cardiocerebral resuscitation protocol for
      managing prehospital cardiac arrest improved survival of adult patients with
      witnessed cardiac arrest and an initially shockable rhythm.

PMID- 16564775
TI  - Impact of anemia on mortality, cognition, and function in community-dwelling
      elderly.
AB  - PURPOSE: To explore the impact of varying hemoglobin levels on mortality,
      function, and cognition in a representative population of older persons. METHODS:
      Participants in this prospective cohort study included 1 744 men and women, aged
      71 years or older, from a random household sample living in Durham and
      surrounding counties in North Carolina. Hemoglobin levels were obtained from
      participants at baseline in 1992. Functional status was measured at the 4-year
      follow-up interview using Katz and instrumental activities of daily living.
      Cognition was measured using the Short Portable Mental Status Questionnaire
      (SPMSQ). Death was determined by search of the National Death Index, and all
      deaths through 2000 are included. RESULTS: Using World Health Organization (WHO)
      criteria, the prevalence of anemia was 24%. There was a strong racial difference
      with an odds ratio, adjusted for age, education, estimated glomerular filtration
      rate and comorbidity of 3.0 (95% CI, 2.3-3.9) in African Americans compared with
      Caucasians. The risk ratio for 8-year mortality was 1.7 (95% CI, 1.5-2.0) for
      anemic subjects (P = .0001) and did not differ by sex or race. Anemia was
      strongly associated with poorer physical function (P = .0001) and cognitive
      function (P = .0001), and predicted decreases in both over a 4-year period.
      CONCLUSIONS: In an elderly community-based population, anemia is more prevalent
      in African Americans and is independently associated with increased mortality
      over 8 years for both races and sexes. Anemia also is a risk factor for
      functional and cognitive decrease.

PMID- 16564777
TI  - Small bowel exploration by wireless capsule endoscopy: results from 314
      procedures.
AB  - OBJECTIVES: To assess the diagnostic efficiency of capsule endoscopy in a large
      group of patients with different indications, to weigh the reliability of the
      procedure for excluding small bowel lesions, and to identify factors associated
      with the likelihood of obtaining a definitive diagnosis. METHODS: Three hundred
      four consecutive patients (141 female, mean age 55 years, range 12-91 years)
      underwent capsule endoscopy in two different Gastroenterology Units, for a total
      of 314 procedures, and were followed-up for a median period of 15 months.
      Referrals were obscure occult/overt gastrointestinal bleeding (203 patients),
      suspected small bowel disease (74), gastrointestinal polyposis (18),
      suspected/previous intestinal or endocrine malignancies (13), previously
      diagnosed intestinal lymphangectasia (3), and vascular abnormalities (3).
      RESULTS: Adequate visualization of the small bowel was obtained in 96% of
      patients, although the capsule did not visualize cecum in 20% of cases. Non
      natural excretion of the capsule was observed in 4 patients, all of whom
      underwent laparotomy for intestinal stenosis. Diagnostic yields were 58% for
      obscure gastrointestinal bleeding and 31% for patients with suspected small bowel
      disease. Capsule endoscopy was able to rule out small bowel disease in 14% of
      patients, and a definitive diagnosis was achieved in 65% of patients. The only
      parameter associated with the likelihood of reaching a conclusive diagnosis was
      the indication to the procedure (overall chi-square 13.5, P = .004). CONCLUSIONS:
      Capsule endoscopy represents a reliable tool for verifying the state of the small
      bowel. Accurate selection of indications and critical evaluation of the results
      are essential to fully exploit this procedure.

PMID- 16564778
TI  - Does the content of primary care visits differ by the racial composition of
      physicians' practices?
AB  - PURPOSE: The study compared the content of primary care visits between physicians
      with larger and smaller African American practices. METHODS: We compared the
      content of primary care adult visits between physicians with larger and smaller
      African American practices using data from the National Ambulatory Medical Care
      Survey and the National Hospital Ambulatory Medical Care Survey 1997 to 2002.
      Larger African American practice (>14% of primary care visits by African
      Americans) was empirically defined to conform with previous studies. RESULTS:
      Larger African American practices comprised 24% of all practices but accounted
      for 80% of all visits by African American patients. In adjusted analyses,
      physicians with larger African American practices were less likely to refer
      patients to specialists (adjusted odds ratio 0.77; 95% confidence internal 0.61
      0.98) and marginally less likely to perform rectal examinations (adjusted odds
      ratio 0.84; 95% confidence interval 0.56-1.00) but were more likely to schedule a
      return appointment (adjusted odds ratio 1.25; 95% confidence interval, 1.02
      1.52). However, there were no other significant differences in the reported
      content of the office visits. Results were not altered when different cutoffs for
      larger African American practices were used or when obstetricians-gynecologists
      were excluded from the analyses. CONCLUSION: There are few differences in the
      content of office visits between physicians with larger and smaller African
      American practices.

PMID- 16564779
TI  - The incidence of stroke after myocardial infarction: a meta-analysis.
AB  - PURPOSE: While the risk of stroke after myocardial infarction (MI) is increased
      compared with the risk among those without MI, the magnitude of this risk remains
      unclear. Although numerous clinical trials have reported the incidence of stroke
      following MI, these are among selected populations. We reviewed cohort studies
      reporting the incidence of stroke after MI to better define the risk of ischemic
      stroke in an unselected population. METHODS: A computerized literature search
      (MEDLINE and PubMed) and manual review of reference lists of identified articles
      were conducted. Population-based studies published from 1978-2004 with at least
      100 subjects that reported number or percent of ischemic strokes experienced by
      MI survivors were identified. Data were extracted using standardized forms, and
      study quality was assessed by 2 independent reviewers. Ischemic stroke rates were
      reported as number of events per 1000 MI with 95% confidence intervals (CI)
      calculated by Poisson distribution. A combined stroke rate was calculated for in
      hospital, 30 days, and 1-year post-MI using weights of 1/variance. A random
      effects model also was created to estimate in-hospital stroke rate. Variability
      in study designs and outcome definitions limit synthesis of available data.
      RESULTS: During hospitalization for the index MI, 11.1 ischemic strokes occurred
      per 1000 MI compared with 12.2 at 30 days and 21.4 at 1 year. Using a random
      effects model, 14.5 strokes occurred per 1000 MI. Positive predictors of stroke
      after MI included: advanced age, diabetes, hypertension, history of prior stroke,
      anterior location of index MI, prior MI, atrial fibrillation, heart failure, and
      nonwhite race. CONCLUSIONS: The public health implications of stroke among MI
      survivors, as well as the large number of MI survivors, underscore the need to be
      aware of this devastating complication. Further research is needed to determine
      the optimal stroke prevention strategies for MI survivors.

PMID- 16564780
TI  - Is there cross-reactivity between penicillins and cephalosporins?
AB  - BACKGROUND: We sought to determine the risk of an allergic reaction to a
      cephalosporin exposure in those with prior penicillin reactions. METHODS: We
      conducted a retrospective cohort study using the United Kingdom General Practice
      Research Database. We selected all patients receiving a prescription for
      penicillin followed by a prescription for a cephalosporin and identified allergic
      like events within 30 days after each prescription. Allergic events were defined
      by 2 sets of codes: 1 more restrictive, 1 more inclusive. Comparison was made
      with a population of patients receiving a prescription for a penicillin followed
      by a prescription for a sulfonamide antibiotic. RESULTS: A total of 3,375,162
      patients received a penicillin; 506,679 (15%) received a subsequent
      cephalosporin. Among patients receiving a penicillin followed by a cephalosporin,
      the unadjusted risk ratio of an allergic-like event for those who had a prior
      event, compared with those who had no such prior event, narrowly defined, was
      10.1 (confidence interval 7.4-13.8). The absolute risk of anaphylaxis after a
      cephalosporin was less than 0.001%. The unadjusted risk ratio for sulfonamide
      antibiotic, rather than cephalosporin after penicillin allergic-like events was
      7.2 (confidence interval 3.8-13.5). CONCLUSION: Patients with allergic-like
      events after penicillin had a markedly increased risk of events after either
      subsequent cephalosporins or sulfonamide antibiotics. Cross-reactivity is not an
      adequate explanation for this increased risk, and the risk of anaphylaxis is very
      low. Thus, our data indicate that cephalosporins can be considered for patients
      with penicillin allergy.

PMID- 16564781
TI  - N-terminal probrain natriuretic peptide and C-reactive protein in stable coronary
      heart disease.
AB  - PURPOSE: C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide
      (NT-proBNP) provide prognostic information in patients with stable coronary heart
      disease. The aim of the study was to investigate whether combined use of NT
      proBNP and CRP improves risk stratification in these patients. METHODS: This
      cohort study included 989 patients with stable coronary heart disease who
      underwent coronary stenting. CRP and NT-proBNP were measured before angiography.
      The primary end point of the study was all-cause mortality. Using median values
      of NT-proBNP (279.9 ng/L) and CRP (1.2 mg/L), patients were divided into 4
      groups: low NT-proBNP-low CRP group (305 patients with NT-proBNP<median and
      CRP<median); low NT-proBNP-high CRP group (190 patients with NT-proBNP<median and
      CRP> or =median; high NT-proBNP-low CRP group (237 patients with NT-proBNP> or
      =median and CRP<median); and high NT-proBNP-high CRP group (257 patients with NT
      proBNP> or =median and CRP> or =median). RESULTS: During a median follow-up of
      3.6 years (interquartile range 3.3 to 4.5 years), there were 85 deaths: 6 deaths
      in the low NT-proBNP-low CRP group, 11 deaths in the low NT-proBNP-high CRP
      group, 20 deaths in the high NT-proBNP-low CRP group, and 48 deaths in the high
      NT-proBNP-high CRP group with Kaplan-Meier mortality estimates of 2.7%, 8.9%,
      12.1% and 35.6%, respectively (P <.001). Cox proportional hazards model showed
      that combination NT-proBNP-CRP was the strongest independent correlate of
      mortality (hazard ratio [HR] 4.3, 95% confidence interval [CI], 2.0-9.3; P <.001
      for high NT-proBNP-high CRP vs low NT-proBNP-low CRP). CONCLUSION: Combined use
      of NT-proBNP and CRP improves long-term risk prediction of mortality in patients
      with stable coronary heart disease.

PMID- 16564782
TI  - Diagnostic performance of 123I-labeled serum amyloid P component scintigraphy in
      patients with amyloidosis.
AB  - PURPOSE: To assess the diagnostic accuracy and additional information provided by
      123I-labeled serum amyloid P component (SAP) scintigraphy in patients with
      systemic and localized amyloidosis. SUBJECTS AND METHODS: 123I-labeled human SAP
      was injected intravenously into 20 controls and 189 consecutive patients with
      histologically proven amyloidosis: of AA type in 60 cases, AL type in 80,
      hereditary ATTR type in 27, and localized amyloidosis in 22 cases. SAP
      scintigrams were obtained 24 hours after tracer injection and were analyzed for
      abnormal patterns of uptake. Sensitivity and specificity were determined, and
      scintigraphic findings were compared with clinical data. RESULTS: Diagnostic
      sensitivity of SAP scintigraphy for systemic AA, AL, and ATTR amyloidosis was
      90%, 90%, and 48% respectively, and specificity was 93%. The distribution of
      amyloid was less diverse in AA than in AL type. Myocardial uptake was not
      visualized in any patient. Splenic amyloid was very frequent (80%) in AA and AL
      type but rarely detected clinically (14%). Abnormal tracer uptake in the liver
      and kidneys correlated with disturbed liver function and proteinuria,
      respectively. Bone marrow uptake was specific for AL (21%) and was more frequent
      in AL kappa than AL lambda. Localized amyloid deposits were not imaged.
      CONCLUSION: SAP scintigraphy is diagnostic of amyloid in most patients with AA
      and AL type but fewer with hereditary ATTR type, relating to differing
      distributions and burdens of amyloid in these disorders. It usually reveals more
      widespread organ involvement than is identified clinically, and certain
      distributions of amyloid are characteristic of particular fibril types.

PMID- 16564783
TI  - Long-term outcome of diffuse proliferative lupus glomerulonephritis treated with
      cyclophosphamide.
AB  - PURPOSE: To report the long-term outcome of diffuse proliferative lupus nephritis
      (DPLN) treated with cyclophosphamide (CYC) in Chinese patients. METHODS: Patients
      with biopsy-proven DPLN treated with prednisolone and CYC were identified. The
      long-term renal outcome and treatment-related toxicities were reported. RESULTS:
      A total of 212 patients were studied (89% women; mean age 30.9 +/- 10.9 years;
      mean system lupus erythematosus [SLE] duration 36.7 +/- 55.1 months). At renal
      biopsy, 148 (70%) patients were nephrotic, and 78 (37%) had impaired serum
      creatinine. One hundred and three (49%) patients received daily oral CYC, whereas
      109 (51%) received intravenous bolus CYC. At last dose of CYC, 126 (59%) patients
      responded completely, and 56 (26%) responded partially. In a logistic regression
      model, the cumulative CYC dose and histologic chronicity score predicted complete
      response. One hundred fifty-five (73%) patients received maintenance
      immunosuppression for at least 3 years (88% azathioprine). After a follow-up of
      1873 patient-years, 66 patients experienced renal flares, 30 had doubling of
      serum creatinine, 18 developed end-stage renal failure, and 14 died. The renal
      survival rates were 88.7%, 82.8% and 70.7% at 5, 10 and 15 years, respectively.
      Failure to respond completely to CYC and the absence of maintenance
      immunosuppression were independent predictors of a poor renal outcome. Ovarian
      toxicity was more frequent with the oral CYC regimen. Increasing age and higher
      cumulative doses of CYC were independent risk factors. CONCLUSIONS: In Chinese
      patients with DPLN, the cumulative dose, rather than the route of CYC
      administration, determines the initial treatment response and ovarian toxicity.
      Maintenance immunosuppression is associated with a better long-term prognosis.
      The oral CYC regimen is more toxic and should be reserved for high-risk patients.

PMID- 16564784
TI  - Trends in the presentation of celiac disease.
AB  - PURPOSE: Screening studies have revealed that celiac disease is common in the
      United States; however, there are scant data on the mode of presentation. We
      analyzed the trends in clinical presentation over the last 52 years in a large
      cohort of biopsy-proven patients seen in 1 center. SUBJECTS AND METHODS: Patients
      (n = 590) were divided into 6 groups based on the year of diagnosis (1952-2004).
      Groups were compared for trends in age at diagnosis, childhood diagnosis,
      duration of symptoms, mode of presentation (diarrhea, bone disease, anemia,
      incidental at esophagogastroduodenoscopy, screening), and presence of malignancy.
      RESULTS: Diagnosis was at an older age since 1980 (P = .007), and there was a
      significant negative linear trend in patients presenting with diarrhea (P<.001)
      over time and a positive linear trend in asymptomatic patients detected on
      screening (P<.001). There was a significant negative linear trend in patients
      with a malignancy (P = .02) and duration of symptoms before diagnosis of celiac
      disease (P = .001), although only the subgroup without diarrhea had improvement
      in delay of diagnosis of celiac disease (assessed by a shorter duration of
      symptoms) (P = .05). Comparison of patients with and without diarrhea showed no
      significant difference in age (42.9 years vs 43.7 years, P = .59), gender (29.3%
      M vs 34.6%, P = .59), and presence of childhood disease (8.0% vs 9.8%, P = .43)
      or malignancies (9.8% vs 8.9%, P = .71). CONCLUSION: There is a trend toward
      fewer patients presenting with symptomatic celiac disease characterized by
      diarrhea and a significant shift toward more patients presenting as asymptomatic
      adults detected at screening.

PMID- 16564785
TI  - Endothelial dysfunction in PCOS: role of obesity and adipose hormones.
AB  - PURPOSE: Polycystic ovary syndrome (PCOS) is an extremely prevalent disorder in
      which elevated blood markers of cardiovascular risk and altered endothelial
      function have been found. This study was designed to determine if abnormal
      carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) in
      young women with PCOS may be explained by insulin resistance and elevated
      adipocytokines. METHODS: A prospective study in 50 young women with PCOS (age:
      25.2 +/- 1 years; body mass index [BMI]: 28.7 +/- 0.8) and 50 matched ovulatory
      controls (age: 25.1 +/- 0.7 years; BMI: 28.5 +/- 0.5) was performed. Carotid IMT,
      brachial FMD, and blood for fasting glucose, insulin, leptin, adiponectin and
      resistin were measured. RESULTS: PCOS, IMT was increased (P <.01), FMD was
      decreased (P <.01), fasting insulin was increased (P <.01), QUICKI (a marker of
      insulin resistance) was decreased (P <.01), and adiponectin was lower (P <.05),
      whereas leptin and resistin were not different compared with matched controls.
      Whereas BMI or waist/hip ratios did not correlate with IMT or FMD, insulin and
      QUICKI correlated positively and negatively with IMT (P <.01). There was a
      significant negative correlation between adiponectin and IMT (P <.05). These
      correlations were unchanged when adjusting for BMI and the correlation between
      IMT and adiponectin was unaffected by insulin resistance parameters. CONCLUSIONS:
      These data suggest that young women with PCOS have evidence for altered
      endothelial function. Adverse endothelial parameters were correlated with insulin
      resistance and lower adiponectin. Both insulin resistance and adiponectin appear
      to be important parameters. It is hypothesized that the type of fat distribution
      may influence these factors.

PMID- 16564787
TI  - Idiopathic renal infarction.
AB  - BACKGROUND: Renal infarction may be an underrecognized disorder. Classical
      teaching holds that cardioemboli, notably in the setting of arterial
      fibrillation, are responsible. The expanding use of contrast enhanced computed
      tomography (CT) in patients with acute abdomen may change the spectrum of renal
      infarction. METHODS: Twenty-seven consecutive patients presenting to a single
      university hospital with nontraumatic CT-documented acute renal infarction were
      studied and stratified according to the presence or absence of cardiac disease,
      either obvious at presentation or detected during work-up. RESULTS: Eleven
      patients (41%) had obvious cardiac disease, including atrial fibrillation in all
      but one. Sixteen patients (59%) had no discernible structural or arrhythmic
      cardiac disease and were classified as idiopathic group. Patients in the
      idiopathic group were significantly younger (median age in years [interquartile
      range]: 48 [41-53] versus 75 [53-82] years, P = .003) and, besides smoking, had
      fewer traditional cardiovascular risk factors. CONCLUSION: Acute renal infarction
      may occur in individuals of middle age without risk factors for cardioembolism.
      In patients with renal colic without lithiasis the diagnosis of renal infarction
      should be considered especially if serum lactate dehydrogenase is elevated, even
      in the absence of atrial fibrillation.

PMID- 16564786
TI  - Lack of value of repeat stool testing for Clostridium difficile toxin.
AB  - Twenty years ago, Clostridium difficile was first established as a cause of
      pseudomembranous colitis and antibiotic-associated diarrhea.C. difficile diarrhea
      is a widely recognized problem in the inpatient setting, with potentially
      significant morbidity and mortality. Antibiotics, and some chemotherapy agents,
      can potentially cause C. difficile colitis/diarrhea. The most commonly implicated
      agents are ampicillin, clindamycin, and cephalosporins. Diarrhea during
      antibiotic therapy is common and may be caused by C. difficile. Testing for C.
      difficile differentiates diarrheas into C. difficile positive and C. difficile
      negative. C. difficile can be carried asymptomatically as normal gastrointestinal
      flora, and in adults who have received antibiotic therapy, carrier states can be
      as high as 46%. Hospitalized patients are often colonized with C. difficile. C.
      difficile produces 3 virulence factors: an enterotoxin (toxin A), a cytotoxin
      (toxin B), and a substance to inhibit bowel motility. Different tests can be used
      to detect these toxins. The most widely used test is the enzyme immunoassay (EIA)
      for toxin A, toxin B, or both. The EIA C. difficile toxin assay has sensitivity
      and specificity ranges of 50% to 90% and 70% to 95%, respectively.
      Diagnostically, C. difficile cell culture cytotoxin assay remains the gold
      standard with sensitivity and specificity of 93% and 89%, respectively. Because
      of lack of confidence of the EIA for C. difficile, some clinicians assume an
      initial negative result may represent a false-negative test, and repeat testing
      is often done. We evaluated the value of repeat stool testing for C. difficile
      toxin A and B by EIA in inpatients with nosocomial diarrhea on antibiotics.

PMID- 16564788
TI  - Strategic planning for departmental divisions in an academic health care center.

PMID- 16564789
TI  - Remission of hepatic metastasis from colon cancer after methotrexate withdrawal.

PMID- 16564790
TI  - Paget-von Schrotter syndrome.

PMID- 16564792
TI  - Regarding the October ECG image of the month.

PMID- 16564793
TI  - Ocular rigidity in patients with age-related macular degeneration.
AB  - PURPOSE: To compare the ocular rigidity in vivo measurements of patients with age
      related macular degeneration (AMD) and control subjects. DESIGN: Prospective
      comparative clinical study. METHODS: The pressure-volume relation and the ocular
      rigidity coefficient were compared among 32 patients with AMD (AMD group: 16 with
      neovascular and 16 with nonneovascular AMD) and 44 age-matched control patients
      (control group) who underwent operation for cataract. This was achieved by an
      injection of 200 microl of a balanced salt solution (in steps of 4.5 microl)
      through the limbus in the anterior chamber, while the intraocular pressure was
      monitored continually with a transducer, up to the limit of 30 mm Hg. RESULTS:
      The mean age (AMD group: 69.89 +/- 15.92 years vs control group: 65.28 +/- 12.34
      years; P = .195), gender (AMD group: 13 female vs control group: 17 female; P =
      .513), eye's axial length (AMD group: 23.14 +/- 0.75 mm vs control group: 23.04
      +/- 1.16 mm; P = .725) of patients with AMD and the healthy control subjects were
      comparable. No statistically significant difference in ocular rigidity
      measurements between patients with AMD and control subjects (AMD group: 0.0142 +/
      0.0077 microl(-1) vs control group: 0.0125 +/- 0.0049 microl(-1); P = .255) was
      found. When we examined separately the two subgroups of patients with AMD
      (neovascular and nonneovascular AMD), the average ocular rigidity measurements
      were higher in patients with neovascular AMD vs both control subjects and
      patients with nonneovascular AMD (neovascular AMD group: 0.0186 +/- 0.0078
      microl(-1) vs control group: 0.0125 +/- 0.0048 microl(-1) [P = .014] vs
      nonneovascular AMD group: 0.0104 +/- 0.0053 microl(-1) [P = .004]). CONCLUSIONS:
      Despite the limitations placed by the small sample of the examined cases,
      patients with neovascular AMD who are treated (with photodynamic therapy) have
      increased ocular rigidity measurements compared with patients with nonneovascular
      AMD and control patients.

PMID- 16564794
TI  - Long-term follow-up of intermediate uveitis in children.
AB  - PURPOSE: To analyze the clinical manifestations, remissions, and visual prognosis
      of intermediate uveitis in children, and to identify the risk factors for poor
      visual outcome. DESIGN: Retrospective cohort study. METHODS: Institutional study
      of 32 consecutive patients examined at a tertiary referral center with
      intermediate uveitis and the onset of ocular disease before the age of 16 years.
      Numerous variables were assessed, including age and gender distribution,
      laboratory data, the presence of systemic diseases, onset and course of ocular
      inflammation, clinical features and complications, therapeutic strategies and
      their outcomes, remission and final visual acuity, and characteristics associated
      with poor visual outcome. RESULTS: Bilateral involvement was observed in 94% of
      the patients. Remission was observed in seven out of 15 patients (47%) with
      completed follow-up of five years. For our 32 subjects, we found a mean time to
      remission of 6.4 years (SE 0.7, CI 5.1 to 7.7). Visual outcome was favorable as
      only three patients developed unilateral acuity of less than 0.1 after five-year
      follow-up, and no additional blind eyes manifested. No associated systemic
      diseases were established. Optic disk edema was the most frequent complication
      observed (71%). Cystoid macular edema (CME) was observed in 44% of the patients
      and was the most common cause of visual loss. CONCLUSIONS: Intermediate uveitis
      of childhood might exhibit a self-limiting course after several years. Visual
      loss was limited despite the high rate of severe ocular complications.

PMID- 16564795
TI  - Small ciliary body tumors: ultrasound biomicroscopic assessment and follow-up of
      42 patients.
AB  - PURPOSE: Detecting and following small tumors of the ciliary body is a particular
      challenge because of their location. Recently high-frequency ultrasound
      biomicroscopy (UBM) has been used to assist in this task. The aim of this study
      was to evaluate this subset of small ciliary body tumors through the use of UBM.
      DESIGN: Retrospective, noncomparative case series. METHODS: Forty-two patients
      with small ciliary body tumors (less than 4 mm) from our institution were
      included in the study with a median follow-up of 4.3 years. UBM was used to
      assess tumor characteristics including height, location, and internal and
      external features. The data were collected longitudinally, and statistical
      analysis was performed. RESULTS: Median initial tumor height was 2.05 mm (range
      1.1 to 3.8 mm) as measured by UBM. By 5 years after diagnosis, five tumors (12%)
      exhibited growth. The overall mean growth rate was 0.026 mm per year (P =
      .00007). The most rapid period of growth was in the first year after diagnosis
      (growth rate 0.128 mm per year), after which the mean tumor size appeared to
      stabilize. CONCLUSIONS: UBM is a valuable tool for detecting and following small
      ciliary body tumors (less than 4 mm), as these lesions may go undetected by other
      methods. Despite the potential for local extension into the iris or choroid, few
      of the tumors in this study exhibited growth, suggesting that many of these
      tumors can be managed conservatively. UBM can be used to assess various internal
      tumor features; however, arriving at a specific diagnosis without histologic
      correlation is difficult.

PMID- 16564796
TI  - Cataract formation and other complications of intravitreal triamcinolone for
      macular edema.
AB  - PURPOSE: To evaluate complications and results of intravitreal triamcinolone
      acetonide for treatment of macular edema. DESIGN: Interventional, consecutive,
      retrospective case series. METHODS: Ninety-three eyes with macular edema arising
      from retinovascular etiologies were treated with 4 mg intravitreal triamcinolone.
      Eyes were monitored after injection for visual acuity changes and complications,
      including cataract formation and increase in intraocular pressure (IOP). Cataract
      progression was analyzed by linear regression analysis of lens scores from lens
      opacity standards. RESULTS: The mean visual acuity improved from 20/125 to -1 to
      20/100 + 2 by one to two months after injection (P < .001) and was 20/100 at the
      final examination (P = .006) at a mean of 1.2 years after injection.
      Complications included a severe, culture-negative inflammatory reaction in one
      eye (1.1%). IOP increased to 30 mm Hg or more in nine (9.7%) of 93 eyes between 1
      and 140 days after injection and was more frequent in eyes receiving one or more
      preinjection glaucoma drops (two of 13 eyes, 15.4%, vs seven of 80 eyes, 8.75%,
      without preinjection glaucoma drops). Nuclear sclerosis increased at a rate of
      0.175 U per year, posterior subcapsular cataracts at 0.423 U per year, and
      cortical cataracts at 0.045 U per year. Posterior subcapsular cataract increased
      by > or = 1 U or required cataract surgery in 45.2% of eyes followed at least one
      year. CONCLUSIONS: Intravitreal triamcinolone improves visual acuity in most eyes
      but eyes must be monitored carefully for increase in IOP. Posterior subcapsular
      cataract formation becomes visually significant in almost half of eyes by one
      year after injection.

PMID- 16564797
TI  - Verteporfin and intravitreal triamcinolone acetonide combination therapy for
      occult choroidal neovascularization in age-related macular degeneration.
AB  - PURPOSE: To evaluate the efficacy and safety of photodynamic therapy (PDT) with
      verteporfin combined with intravitreal triamcinolone (IVTA) in occult choroidal
      neovascularization (CNV) secondary to age-related macular degeneration (AMD).
      DESIGN: Single center, nonrandomized interventional case series. METHODS: A
      prospective, noncomparative, interventional case series of 41 eyes of 41 patients
      with a two-year follow-up period. Verteporfin PDT was performed using the
      recommended standard procedure for approved forms of AMD. A solution containing
      25 mg of crystalline triamcinolone acetonide was injected intravitreally 16 hours
      post PDT. The procedure was repeated after three months in case of persistent CNV
      leakage. RESULTS: The mean number of treatments needed was 1.8. Thirty-four eyes
      (82.9%) required one retreatment at three months. No additional retreatments were
      necessary. Visual acuity improved gradually in most of the patients with mean
      values of 20/133 and 20/115 at baseline and three months; 20/101 and 20/84 at six
      and twelve months; and 20/83 and 20/81 at eighteen and twenty-four months. Eleven
      of 41 treated study eyes (26.8%) underwent cataract surgery between six and
      fifteen months after the first treatment. Nine patients required local or
      systemic glaucoma therapy because of a transient steroid induced intraocular
      pressure increase. CONCLUSIONS: Verteporfin PDT combined with intravitreal
      triamcinolone may improve the outcome of standard verteporfin PDT in the
      treatment of occult CNV secondary to AMD. An improvement in visual acuity was
      observed in most of the treated patients and was maintained during a two-year
      follow-up period. Retreatment numbers were lower than expected from monotherapy
      trials.

PMID- 16564798
TI  - A randomized, masked, cross-over trial of lisinopril for inflammatory macular
      edema.
AB  - PURPOSE: To analyze the effect of angiotensin-converting enzyme (ACE) inhibitor
      lisinopril on inflammatory cystoid macular edema and visual acuity. DESIGN:
      Randomized, double-blind, placebo-controlled cross-over trial. METHODS: setting:
      Outpatient clinic of the Department of Ophthalmology at the University Medical
      Center of Utrecht. patients: Forty patients with inflammatory cystoid macular
      edema were included. intervention: Each patient received lisinopril (10 mg daily)
      or placebo for three months. After two months of a lisinopril/placebo free wash
      out period, the groups received the reverse study medication for three months.
      Fluorescein angiography was performed to evaluate the retina. main outcome
      measures: Cystoid macular edema, best-corrected visual acuity and contrast
      sensitivity. RESULTS: Lisinopril had no effect on cystoid macular edema, visual
      acuity, papillary leakage, retinal vasculitis, and choroidal leakage. In a
      subgroup analysis, we observed a decrease in blood pressure (lisinopril, 14 of 36
      patients; placebo, 5 of 36 patients; P = .02) and a decrease in morning urinary
      albumin excretion (lisinopril, 23 of 35 patients; placebo 10 of 34 patients, P =
      .003) was observed. CONCLUSIONS: Although lisinopril had no effect on
      inflammatory cystoid macular edema and visual acuity, we found a positive effect
      on the vascular system.

PMID- 16564799
TI  - Trabeculectomy with mitomycin C in pseudophakic patients with open-angle
      glaucoma: outcomes and risk factors for failure.
AB  - PURPOSE: To evaluate tonometric outcomes of trabeculectomy with mitomycin C in
      pseudophakic patients with open-angle glaucoma and associated risk factors for
      failure. DESIGN: Retrospective cohort study. METHODS: Seventy-three pseudophakic
      patients (89 eyes) with primary open-angle, normal-tension, exfoliative, or
      pigmentary glaucoma were recruited. Success rates were defined according to three
      criteria: (A) intraocular pressure (IOP) < or = 18 mm Hg and IOP reduction > or =
      20%; (B) IOP < or = 15 mm Hg and IOP reduction > or = 25%; and (C) IOP < or = 12
      mm Hg and IOP reduction > or = 30%. IOP, visual acuity, complications, and
      additional interventions were documented after surgery. Cox's proportional hazard
      regression analysis was used to identify risk factors for failure. RESULTS: Mean
      IOP (+/-SD) decreased from a preoperative value of 18.8 +/- 6.6 mm Hg to 10.2 +/-
      5.1 mm Hg at one year and to 10.0 +/- 4.2 at two years (P < .001 for both).
      Average number of preoperative medications decreased from 3.0 +/- 1.1 to 0.5 +/-
      1.0 at one year and to 0.5 +/- 0.9 at two years (P < .001 for both). For criteria
      A, B, and C, success rates (+/-SE) were 87% +/- 4%, 83% +/- 5%, and 76% +/- 5% at
      1 year and 67% +/- 4%, 58% +/- 8%, and 50% +/- 7 at two years. Laser suture lysis
      was performed in 30 eyes, and 11% of those required a second glaucoma procedure.
      CONCLUSION: Increasing age, use of a limbus-based conjunctival flap, and
      performance of laser suture lysis were factors that were associated with a
      smaller risk of failure. Present findings indicate that trabeculectomy with
      mitomycin C provides acceptable long-term success rates in pseudophakic patients,
      with a low incidence of complications.

PMID- 16564800
TI  - Conventional and wavefront-guided myopic LASIK retreatment.
AB  - PURPOSE: To assess the clinical outcomes of conventional and wavefront-guided
      myopic laser in situ keratomileusis (LASIK) retreatment. DESIGN: Retrospective,
      nonrandomized case series. METHODS: The study comprised a cohort of 97 eyes
      having LASIK retreatment for residual myopia after primary LASIK. The eyes were
      divided into two groups: conventional retreatment (CR) group (n = 74) and
      wavefront-guided retreatment (WR) group (n = 23). The retreatment LASIK was
      performed using LADARVison 4000 with/without CustomCornea (Alcon Surgical,
      Orlando, Florida, USA). The mean follow-up was 8.9 +/- 5.8 months after
      retreatment (range three to thirty-six months). RESULTS: The mean pre-retreatment
      spherical equivalent (SE) was -0.93 +/- 0.41 diopters in the CR group and -0.84
      +/- 0.48 diopters in the WR group (P = .409). At the last visit, the mean SE was 
      0.19 +/- 0.28 diopters and +0.32 +/- 0.47 diopters, respectively (P < .001). An
      SE of +/- 0.50 diopters was achieved in 92% (68 of 74) of CR eyes and 65% (15 of
      23) of WR eyes. In the CR group, 85% eyes had a uncorrected visual acuity (UCVA)
      > or = 20/20 and 99% > or = 20/40, and in the WR group, 35% and 100%,
      respectively. None of the CR eyes and 17% (4 of 23) of WR eyes lost two lines of
      best spectacle-corrected visual acuity (BSCVA). Nine percent (7 of 74) of CR eyes
      and 30% of WR eyes (7 of 23) had optical symptoms before retreatment, the number
      was reduced to 1% (1 of 74) and 4% (1 of 23), respectively. CONCLUSIONS: In the
      study period with the current equipment, our results showed that conventional
      LASIK retreatment was superior to wavefront-guided LASIK retreatment in both
      efficacy and safety.

PMID- 16564801
TI  - Marx line: fluorescein staining line on the inner lid as indicator of meibomian
      gland function.
AB  - PURPOSE: To determine whether the location of a fluorescein-stained line, the
      Marx line (ML), which runs along the inner eyelid, is correlated with meibomian
      gland function. DESIGN: Prospective observational case series. METHODS: After
      applying fluorescein dye solution to the eye, the ML score was calculated for the
      outer, middle, and inner thirds of the lower eyelid margin. ML scoring was as
      follows: 0, entirely on the conjunctival side of the meibomian orifices (MOs); 1,
      part of the ML touches the MOs; 2, ML runs through all of the MOs; and 3, ML runs
      on the eyelid-margin side of the MOs. Correlations were calculated between the
      total ML score and age for 251 randomly recruited subjects without acute ocular
      surface diseases, and between age and the ML score for the three regions of the
      lower eyelid. Correlations between the regional ML score and the meibographic
      score, and the meibomian gland secretion score were also determined. The total ML
      scores of 15 subjects without meibomian gland dysfunction (MGD) were compared
      with 15 age-matched patients with MGD. RESULTS: The three regions of the lower
      eyelid had significantly different ML scores. Strong correlations were found
      between the ML score and age, the meibographic score, and the meibomian gland
      secretion score. The total ML score of MGD group was significantly higher than
      that of the non-MGD group. CONCLUSIONS: The strong correlation between the ML
      score and the meibomian gland scores indicates that the ML score can be used as a
      simple and rapid screening score for meibomian gland function.

PMID- 16564802
TI  - Influence of mutation type on clinical expression of Leber hereditary optic
      neuropathy.
AB  - PURPOSE: The aim of this research was to determine the molecular factors of
      influence on the clinical expression of Leber hereditary optic neuropathy (LHON),
      which might aid in counseling LHON patients and families. The prevalence of LHON
      in the Dutch population was determined. DESIGN: Observational, retrospective
      population cohort study. METHODS: The clinical characteristics of LHON patients
      of 25 families, previously described in 1963, were reevaluated. The mutation and
      haplotype were determined in the DNA of one affected LHON patient per family. The
      genotype of their relatives could be deducted, enabling us to evaluate
      retrospectively the genotype-phenotype correlation. The prevalence of LHON was
      determined on the basis of anamnestic evaluation of patients in 1963 and by using
      population registers of that period. RESULTS: The LHON mutation does not
      influence disease penetrance (50% in male subjects; 10% to 20% in female
      subjects). More than half of the patients with the 14484 mutation exhibit a
      partial recovery of vision, regardless of the acuteness of disease onset (P =
      .001), whereas only 22% of the 11778 carriers and 15.4% of the 3460 carriers
      recovered. The recovery did not take place within the first year after onset and
      was uncommon after four years. The onset of LHON is in general very acute but
      might be more gradual in 11778 carriers and in children. The calculated
      prevalence of LHON in the Dutch population (1/39,000) is very likely an
      underestimation caused by a selection bias of familial cases in the original
      study. CONCLUSIONS: The LHON genotype influences the recovery of vision and
      disease onset but is unrelated to age, acuteness of onset, or gender. The
      genotype does not influence disease penetrance. Children might exhibit a slower
      onset of disease.

PMID- 16564803
TI  - Bilateral lateral rectus recession versus unilateral recess-resect procedure for
      exotropia with a dominant eye.
AB  - PURPOSE: To compare the surgical outcomes of bilateral lateral rectus recession
      and unilateral recess-resect (RR) procedure on the nondominant eye for the
      patients of exotropia with a dominant fixating eye. DESIGN: Prospective
      randomized comparative clinical trial. METHODS: One hundred twenty-four patients
      of exotropia with an invariably fixating eye were enrolled to this study.
      Patients were assigned randomly to two groups, those who underwent bilateral
      lateral rectus (BLR) recessions (BLR group) or unilateral RR procedures on the
      nondominant eye (RR group); surgical outcomes were compared. An outcome was
      considered satisfactory if there was between 10 prism diopters of
      exophoria/tropia and 10 prism diopters of esophoria/tropia at 6 months after
      surgery. RESULTS: In the BLR group, 28 of the 58 patients (48.3%) had a
      satisfactory outcome, and 30 patients (51.7%) had recurrence. There was no case
      of overcorrection in the BLR group. In the RR group, 55 of the 66 patients
      (83.3%) had a satisfactory outcome; 6 patients (9.1%) had recurrence, and 5
      patients (7.6%) were overcorrected (P < .001, Fisher's exact test). All
      overcorrected patients in the RR group had poor stereoacuity and constant
      exotropia before the operation. The cumulative probability of surgical success
      was significantly higher in the RR group than in the BLR group (P = .012, log
      rank test). CONCLUSIONS: In the patients with exotropia with a dominant eye, the
      unilateral RR procedure resulted in a better outcome than BLR recession surgery.
      But, the overcorrection rate was significantly higher in the unilateral RR
      procedure group, especially in those patients with a poor preoperative stereopsis
      status and constant exotropia.

PMID- 16564804
TI  - Changes in lumen width of nasolacrimal drainage system after adrenergic and
      cholinergic stimulation.
AB  - PURPOSE: To determine the effect of an adrenergic agonist and a cholinergic
      agonist on the lumen width of the nasolacrimal drainage system. DESIGN:
      Prospective, nonrandomized, clinical trial. METHODS: The asymptomatic sides of 33
      patients (23 women, 10 men) with unilateral stenosis/obstruction of the
      nasolacrimal drainage system were studied. The tear meniscus height of the
      asymptomatic side was normal, with a patent lacrimal system as revealed by
      dacryocystography. The nasolacrimal drainage system of the asymptomatic side was
      infused with 100 microL of 5% phenylephrine hydrochloride (an alpha-1
      adrenoceptor agonist) or 100 microL of 2% pilocarpine hydrochloride (a
      cholinergic agonist), and dacryocystography was performed to determine the lumen
      width of the nasolacrimal drainage system. RESULTS: Phenylephrine caused a
      significant increase of the lumen width of the nasolacrimal drainage system, and
      the changes were more marked in the nasolacrimal duct (NLD), especially the upper
      and middle regions, than in the lacrimal sac. In contrast, pilocarpine reduced
      the lumen width of the NLD significantly, especially in the middle and lower
      regions, and the lumen width of the lacrimal sac was not significantly changed.
      CONCLUSION: The alterations of the lumen width of the nasolacrimal drainage
      system, especially the lumen width of the NLD by adrenergic and cholinergic
      agonists, suggest that the lumen width can be changed by the autonomic nervous
      system.

PMID- 16564805
TI  - The effect of axial length on photodynamic therapy.
AB  - PURPOSE: To determine the effect of the axial length of the eye on photodynamic
      therapy (PDT) light fluence. DESIGN: Laboratory investigation. METHODS: A
      calibrated Gullstrand-type model eye was used for this study. The axial length of
      the model eye was set to different values ranging from 20 to 31 mm, and the light
      fluence rate for treating a spot of 4 mm was recorded and compared with a fluence
      rate of 600 mW/cm2 with four indirect condensing laser lenses. RESULTS: The axial
      length of the eye is inversely related to light fluence. From myopia to
      hyperopia, the total deviation from 600 mW/cm2 was -37.7% to +53.8% (Mainster
      Standard; Ocular Instruments Inc, Bellevue, Washington, USA), and -48.3% to
      +20.5% (Mainster Wide Field; Ocular Instruments Inc), -52.3% to +16.7% (Volk
      Transequator; Volk Optical Inc, Mentor, Ohio, USA), and -52.3% to +15.3% (Volk
      PDT Laser; Volk Optical Inc). CONCLUSIONS: Axial length of the eye has a
      considerable effect on PDT light fluence rate in this model. These findings may
      be important for optimizing PDT, particularly in eyes with high refractive
      errors.

PMID- 16564806
TI  - Inter-eye comparison of patterns of visual field loss in patients with
      glaucomatous optic neuropathy.
AB  - PURPOSE: To compare inter-eye patterns of visual field (VF) loss on standard
      automated perimetry (SAP) in patients with glaucomatous optic neuropathy. DESIGN:
      Observational cross-sectional study. METHODS: Four-hundred-and-ninety eyes of 245
      patients with glaucomatous optic neuropathy in at least one eye defined by masked
      stereophoto review were included. Patients had two reliable SAP visual fields
      within fifteen months for each eye. Patterns of visual field loss were classified
      independently by two graders masked to all other patient information. Patterns
      were described as altitudinal, arcuate, partial arcuate, paracentral, nasal step,
      temporal wedge, or normal based on the classification system of Keltner and
      associates. Superior and inferior hemifields were graded separately. RESULTS:
      Inter-grader agreement in visual field patterns before adjudication was 97% and
      94% for the worse eye (superior and inferior hemifield) and 97% and 95% for the
      better eye (superior and inferior hemifield). The percentage of correspondence by
      hemifield location was: 53% (superior-superior), 62% (inferior-inferior), 45%
      (superior-inferior), and 55% (inferior-superior). The highest correspondence of
      individual glaucomatous VF pattern between eyes was for arcuate (superior
      superior) and inferior partial arcuate (inferior-inferior) defects (24% and 26%,
      respectively). Smaller hemifield patterns showed lower correspondence between the
      eyes (nasal step, paracentral, temporal wedge, 0% to 13% correspondence).
      CONCLUSIONS: Patterns of visual field loss between eyes often corresponded within
      the same VF hemifield (superior-superior, inferior-inferior) as well as between
      opposite hemifields (inferior-superior), although opposite hemifield
      correspondence was less common. More advanced visual field defects (for example,
      partial arcuate) showed higher correspondence rates between the eyes than less
      advanced defects.

PMID- 16564807
TI  - Corneal and conjunctival manifestations in Fabry disease: in vivo confocal
      microscopy study.
AB  - PURPOSE: To describe the microscopic corneal and conjunctival findings in
      patients with Fabry disease (FD) related keratopathy by using in vivo confocal
      microscopy. DESIGN: Prospective observational case series. METHODS: Twelve eyes
      of six patients affected by Fabry disease, belonging to two different families,
      underwent in vivo confocal microscopic examination. Corneal and conjunctival
      morphology were assessed by means of a scanning slit corneal confocal white-light
      microscopy and confocal laser-scanning microscope. RESULTS: Confocal microscopy
      examination evidenced two different types of corneal epithelial changes. The
      three hemizygous patients presented bright hyper-reflective intracellular
      inclusions located within the basal epithelial cells, while the three
      heterozygous patients showed fine diffusion of reflective substance at the level
      of superficial, basal epithelial cells and basal membrane, in all eyes. The
      complex basal-Bowman's membrane appeared irregular, distorted, and nonhomogeneous
      in all subjects. Stromal increased reflectivity attributable to haze and
      epithelial ingrowth with bright intracellular inclusions was noticed in one
      hemizygous patient. In all patients, conjunctival epithelial involvement
      represented by bright roundish intracellular inclusions was evidenced, appearing
      more pronounced in tarsal than in bulbar conjunctiva. CONCLUSIONS: Although FD
      related cornea verticillata attributable to glycosphingolipids accumulation is
      considered to be primarily a corneal disease, in vivo confocal microscopy
      demonstrated structural alterations throughout the entire ocular surface
      epithelia. It is still unclear whether the different type of corneal epithelial
      lesions observed for hemizygous and heterozygous patients is related to different
      physiopathological mechanisms. Confocal microscopy may assist ophthalmologists in
      the diagnosis of FD-related ocular surface and corneal manifestations.

PMID- 16564808
TI  - Optical coherence tomography of enucleated human eye specimens with histological
      correlation: origin of the outer "red line".
AB  - PURPOSE: To further define the origin of the "outer red line" (ORL) present in
      retinal optical coherence tomograms. DESIGN: Laboratory investigation. METHODS:
      Eleven formalin-fixed caps of seven human eyes previously enucleated for
      choroidal melanoma at the Wilmer Eye Institute were studied. The ORL evaluation
      consisted of sequential, surgical elimination of the retinal pigment epithelium,
      Bruch's membrane (BM), and choroid in separate, but adjacent, areas. Optical
      coherence tomography (OCT) images through each of these areas were correlated
      with corresponding histologic sections. The relative contribution of the retinal
      pigment epithelium, BM, and choroid to the ORL in retinal OCT3 images was
      evaluated. RESULTS: In the specimens examined, the ORL correlated anatomically
      with a highly reflective optical surface at the level of the outer retina, and
      did not appear to represent a specific anatomic layer. The reflecting layers
      appeared to be composed of the retinal pigment epithelium, BM, and inner choroid.
      The relative contribution of BM together with the inner choroid to the ORL
      appeared greater than that of the retinal pigment epithelium. CONCLUSIONS: This
      study suggests that the ORL present in retinal OCT3 images and generally
      associated with the retinal pigment epithelium/BM/inner choroidal complex appears
      to indicate a highly reflective optical surface which, when eye layers are
      normally configured, represents this complex of anatomic structures with a
      predominant contribution from BM and inner choroid. The findings of this study
      suggest a potential role for OCT in the eye pathology laboratory.

PMID- 16564810
TI  - The enigma of pars planitis, revisited.

PMID- 16564811
TI  - Scleral rigidity and macular degeneration: pathophysiologic or epiphenomenon?

PMID- 16564812
TI  - Avoidance, recognition, and management of LASIK complications.
AB  - PURPOSE: To provide important concepts of the latest developments in laser in
      situ keratomileusis (LASIK) complication avoidance, recognition, and management.
      DESIGN: A perspective. METHODS: A comprehensive literature search and review of a
      total of 816 publications that discussed LASIK complications from 1992 to 2005
      was conducted. RESULTS: The risk of visually threatening complications is
      inherent in any ophthalmologic surgical procedure. Not only does LASIK require
      the use of several complex medical devices, but there can be significant human
      variation in response to this surgical intervention. As a result, many potential
      complications can occur after LASIK. The risk of many complications can be
      mitigated by appropriate patient selection and preoperative, surgical, and
      postoperative care. Unforeseen complications will occur, despite meticulous
      planning, and must be managed. Important current developments in the avoidance,
      recognition, and management of LASIK complications are reviewed. CONCLUSIONS:
      Complications as a result of LASIK can threaten vision and may cause debilitating
      symptoms in an otherwise healthy eye. Advancing our understanding of the
      prevention and management of the complications of LASIK is an endeavor that must
      be continued as long as refractive surgery is performed.

PMID- 16564813
TI  - Optical coherence tomography of peripheral retinal lesions in enucleated human
      eye specimens with histologic correlation.
AB  - PURPOSE: To report optical coherence tomography (OCT) histologic correlations of
      three common peripheral retinal lesions and to explore the feasibility of the use
      of OCT to image retinal pathologic conditions in fixed tissue specimens. DESIGN:
      Experimental study. METHODS: We studied peripheral retinal lesions that were
      available to us in 11 formalin-fixed caps of seven human eyes that had been
      enucleated previously for choroidal melanoma. OCT scans were performed through
      these lesions, and the images were correlated with corresponding histologic
      sections. RESULTS: Three peripheral retinal diseases that included cystoid
      degeneration, localized retinal detachment, and paving stone degeneration were
      imaged successfully, and their optical characteristics correlated well with their
      histologic data. CONCLUSION: We explored potential utility for OCT imaging of
      peripheral retinal pathologic conditions in fixed tissue specimens. That these
      OCT images correlate with findings from histologic sections suggests a possible
      role for OCT in the eye pathology laboratory.

PMID- 16564814
TI  - The effect of the timing of scleral flap suture release on the safety and long
      term success of phacotrabeculectomy.
AB  - PURPOSE: To investigate the effect of the timing of the scleral flap suture
      release on the safety and long-term success of phacotrabeculectomy. DESIGN:
      Retrospective, nonrandomized chart review. METHODS: We studied 173 eyes of 173
      consecutive patients who underwent primary phacotrabeculectomy, with or without
      intraoperative mitomycin-C, and subsequent scleral flap suture release. RESULTS:
      Early suture release (<3 weeks) had a lower long-term success rate than late
      suture release (>3 weeks), with an average follow-up period of 44.8 months.
      Patients who used mitomycin-C had statistically later suture release than did
      patients without mitomycin-C. There were nine cases of hypotony, for which
      independent risk factors were early suture release and the use of mitomycin-C.
      CONCLUSIONS: Greater long-term success with minimal complications was achieved
      when scleral flap suture release was performed three weeks after
      phacotrabeculectomy. Suture release within three weeks after surgery was
      associated with an increased risk of filtration failure and a higher risk of
      postoperative complications.

PMID- 16564815
TI  - Climatic droplet keratopathy in the Argentine Patagonia.
AB  - PURPOSE: To present the findings of climatic droplet keratopathy (CDK) that
      affects people of a rural area of the Argentine Patagonia. DESIGN: Observational
      case series. METHODS: Five hundred seventy-seven individuals who live in
      settlements and villages in an inland area of the northwest Patagonia region in
      Argentina received a complete eye examination. RESULTS: The mean age was 36.02
      years (r = 1.5 months to 89 years); 55.63% of the patients were female. The mean
      age of the 7.62% of the patients who had typical CDK was 65.31 years (r = 42 to
      89 years); 86.36% of the patients were male. Of 66 eyes in 35 patients with CDK,
      35 eyes had peripheral haziness (grade 1); 23 eyes had a band-shaped haziness
      (grade 2), and 8 eyes had the aggregate of yellow subepithelial droplets (grade
      3). Pinguecula, pterygium, cataract, and pseudoexfoliation were frequent findings
      among patients with CDK. CONCLUSION: CDK is not infrequent among male adults in
      this area of the Argentine Patagonia and may be severely handicapping.

PMID- 16564816
TI  - Hypermetropia is not associated with hypertension: the Blue Mountains Eye Study.
AB  - PURPOSE: An association between hypermetropia and hypertension was recently
      reported. We sought to verify this finding in the Blue Mountains Eye Study cohort
      (n = 3654; ages 49 to 97 years). DESIGN: Cohort study. METHODS: We defined
      hypermetropia as mean spheric equivalent refraction (SER) > 1.00 diopter, myopia
      as mean SER < -1.00 diopters, and emmetropia as mean SER < or = 1.00 diopters and
      > or = -1.00 diopters, inclusive. We used the 2003 World Health
      Organization/International Society of Hypertension guidelines to define severe
      hypertension as grade 2 or higher. RESULTS: Of 1290 people who were at risk of
      the development of hypertension, 378 people developed incident severe
      hypertension after five years. The multivariate-adjusted relative risk of
      incident hypertension in persons with hypermetropia compared with those with
      emmetropia was 1.06 (95% CI, 0.89 to 1.26); the relative risk in persons with
      myopia was 1.22 (95% CI, 0.96 to 1.56). CONCLUSION: Neither hypermetropia nor
      myopia was associated with incident hypertension in this older population.

PMID- 16564817
TI  - In vivo histology of cotton-wool spots using high-resolution optical coherence
      tomography.
AB  - PURPOSE: To provide optical characteristics of cotton-wool spots (CWS) on optical
      coherence tomography (OCT) and scan the retina after CWS have ophthalmoscopically
      disappeared. DESIGN: Observational case reports. METHODS: We studied four eyes of
      four patients with retinopathy due to human immunodeficiency virus (HIV) and
      hypertension. The StratusOCT Model 3000 in single-line mode was used for imaging
      of acute and resolved CWS and adjacent normal retina. The fundus photography
      served as a template for OCT scanning in localization of CWS. Retinal tissue
      reflectivity images were compared. RESULTS: There were differences in
      reflectivity of normal retina, the retina in the area of active CWS, and the
      retina in the same area after CWS has resolved. Most striking was that the OCT
      documented a persistent focal area of hyper-reflectivity in the area of the
      resolved CWS, indicative of retinal gliosis that could be imaged. CONCLUSIONS:
      CWS show a hyper-reflective pattern on OCT that persists even after they become
      ophthalmoscopically invisible.

PMID- 16564818
TI  - Autosomal dominant cataract: intrafamilial phenotypic variability, interocular
      asymmetry, and variable progression in four Chilean families.
AB  - PURPOSE: To document intrafamilial and interocular phenotypic variability of
      autosomal dominant cataract (ADC). DESIGN: Prospective observational case series.
      METHODS: We performed ophthalmologic examination in four Chilean ADC families.
      RESULTS: The families exhibited variability with respect to morphology, location
      with the lens, color and density of cataracts among affected members. We
      documented asymmetry between eyes in the morphology, location within the lens,
      color and density of cataracts, and a variable rate of progression. CONCLUSIONS:
      The cataracts in these families exhibit wide intrafamilial and interocular
      phenotypic variability, supporting the premise that the mutated genes are
      expressed differentially in individuals and between eyes; other genes or
      environmental factors may be the bases for this variability. Marked progression
      among some family members underscores the variable clinical course of a common
      mutation within a family. Like retinitis pigmentosa, classification of ADC will
      be most useful if based on the gene and specific mutation.

PMID- 16564819
TI  - Retinal pigment epithelial tear following intravitreal pegaptanib sodium.
AB  - PURPOSE: To report two cases of a retinal pigment epithelial tear after
      intravitreal injection of pegaptanib sodium. To our knowledge, this is the first
      report of this finding after intraocular antivascular endothelial growth factor
      therapy. DESIGN: Observational case reports. METHODS: Two patients presented with
      occult choroidal neovascularization and associated serous pigment epithelial
      detachment that was a result of age-related macular degeneration. Both patients
      were treated with an intravitreal injection of pegaptanib sodium. RESULTS: One
      patient developed a retinal pigment epithelium tear one week after the
      intravitreal injection. The second patient developed a retinal pigment epithelium
      tear eight weeks after treatment. CONCLUSIONS: Although these cases may represent
      natural history, there should be a high index of suspicion for retinal pigment
      epithelium tears in patients who report significant visual deterioration after
      intravitreal injection of pegaptanib sodium. Further studies are needed to
      determine whether angiographic subtypes of choroidal neovascular membranes are
      more susceptible to developing retinal pigment epithelium tears after treatment
      with antivascular endothelial growth factor agents.

PMID- 16564820
TI  - Hypothermia of 8 degrees C protects cultured retinal pigment epithelial cells and
      retinal ganglion cells against trypan blue toxicity.
AB  - PURPOSE: To determine whether hypothermia of 8 degrees C can protect cultured
      human retinal pigment epithelial (ARPE-19) cells and rat retinal ganglion cells
      (RGC-5) against trypan blue (TB) toxicity. DESIGN: Laboratory investigation.
      METHODS: ARPE-19 cells and RGC-5 were exposed to balanced salt solution as
      controls, and 0.05% and 0.5% TB at 37 degrees C, and at 8 degrees C for one
      minute. The percentage of surviving cells was determined by the resazurin test.
      RESULTS: TB induced a statistically significant decrease in the percentage of
      ARPE-19 cells surviving at 0.5% TB at 37 degrees C (P < .01). Conversely, TB
      induced a statistically significant decrease in the percentage of RGC-5 surviving
      at all conditions except for 0.05% TB at 8 degrees C (0.05% 37 degrees C; P <
      .05, 0.5% 37 degrees C and 8 degrees C; P < .01). CONCLUSIONS: These results
      indicate that reducing the temperature to 8 degrees C has a protective effect
      against the TB toxicity for ARPE-19 cells and RGC-5 in culture.

PMID- 16564821
TI  - Rose bengal and lissamine green inhibit detection of herpes simplex virus by PCR.
AB  - PURPOSE: To determine whether rose bengal and lissamine green affect polymerase
      chain reaction (PCR) detection of herpes simplex virus (HSV). DESIGN: Laboratory
      investigation. METHODS: Diagnostic corneal scrapings were evaluated for PCR
      inhibitory activity. Dacron swabs inoculated with rose bengal and lissamine green
      were processed as clinical samples, inoculated with control HSV, varicella zoster
      (VZV), cytomegalovirus (CMV), and toxoplasma DNA and prepared for PCR. The
      effects of calcium alginate and cotton swabs were also evaluated. RESULTS: Rose
      bengal, lissamine green, and calcium alginate not only inhibit PCR detection of
      HSV DNA, but also detection of VZV, CMV, and toxoplasma DNA. This inhibition
      could be overcome by serial dilution and by DNA purification of the sample before
      PCR. CONCLUSIONS: Rose bengal, lissamine green, and calcium alginate can inhibit
      PCR detection of HSV DNA. Clinical scrapings to be sent for PCR diagnostic
      testing should be taken before instillation of rose bengal or lissamine green.

PMID- 16564823
TI  - Ocular trauma score in deadly weapon-related open-globe injuries.
AB  - PURPOSE: To assess prognostic value of the ocular trauma score (OTS) in deadly
      weapon-related open-globe injuries. DESIGN: Retrospective, interventional case
      series. METHODS: In 82 patients (88 eyes) with deadly weapon-related open-globe
      injuries, certain numerical values rendered to the OTS variables (visual acuity,
      rupture, endophthalmitis, perforating injury, retinal detachment, afferent
      pupillary defect) at presentation were summated and converted into OTS
      categories. The likelihood of the final visual acuities in the OTS categories
      were calculated and compared with those in the OTS study. RESULTS: The likelihood
      of the final visual acuities (no light perception NLP, light perception LP/hand
      motion HM, 1/200 to 19/200, 20/200 to 20/50, and > or = 20/40) in the OTS
      categories (1 through 5) in this group were similar to those in the OTS study
      group except for LP/HM in the category-2 (53% vs 26%, P < .001). No study eye was
      in the category-5 (the best prognosis). CONCLUSIONS: OTS calculated at initial
      examination may provide prognostic information in deadly weapon-related open
      globe injuries.

PMID- 16564822
TI  - Correlations in a change in aqueous tear evaporation with a change in relative
      humidity and the impact.
AB  - PURPOSE: To establish scientific relationship between relative humidity (RH) and
      aqueous tear evaporation to elucidate possible significance of this relationship
      in normals and aqueous tear deficiency patients. DESIGN: Prospective experimental
      laboratory study. METHODS: Ocular surface evaporation was determined using
      evaporometry and calculated for two ranges of RH, 25% to 35%, and 35% to 45% in a
      randomized clinical patient population. RESULTS: Average evaporative rate in the
      higher humidity range was between 0.029 +/- 0.009 through 0.043 +/- 0.016
      microl/cm2/min. At lower humidity, range was between 0.044 +/- 0.013 through
      0.058 +/- 0.018 microl/cm2/min. Differences in the corresponding evaporative
      rates were statistically significant (between P < .003 through P < .043) for each
      analysis. CONCLUSIONS: A decrease of 10% RH resulted in an average difference of
      between 28.33% to 59.42% increase in evaporation. The increase in evaporation at
      lower humidity has significant clinical implications for patients with aqueous
      deficient dry eyes, and possibly those undergoing laser-assisted in situ
      keratomileusis (LASIK).

PMID- 16564824
TI  - Novel single-base deletional mutation in major intrinsic protein (MIP) in
      autosomal dominant cataract.
AB  - PURPOSE: To further elucidate the cataract phenotype, and identify the gene and
      mutation for autosomal dominant cataract (ADC) in an American family of European
      descent (ADC2) by sequencing the major intrinsic protein gene (MIP), a candidate
      based on linkage to chromosome 12q13. DESIGN: Observational case series and
      laboratory experimental study. METHODS: We examined two at-risk individuals in
      ADC2. We PCR-amplified and sequenced all four exons and all intron-exon
      boundaries of the MIP gene from genomic and cloned DNA in affected members to
      confirm one variant as the putative mutation. RESULTS: We found a novel single
      deletion of nucleotide (nt) 3223 (within codon 235) in exon four, causing a
      frameshift that alters 41 of 45 subsequent amino acids and creates a premature
      stop codon. CONCLUSIONS: We identified a novel single base pair deletion in the
      MIP gene and conclude that it is a pathogenic sequence alteration.

PMID- 16564826
TI  - Treatment of choroidal neovascularization through the implantable miniature
      telescope.
AB  - PURPOSE: To report a case of thermal laser photocoagulation of a choroidal
      neovasacular membrane through the implantable miniature telescope (IMT). DESIGN:
      Interventional case report. METHODS: Focal thermal laser photocoagulation was
      performed. Complete ablation of the neovascular lesion, visual acuity, and
      integrity of the IMT were assessed. RESULTS: An 81-year-old woman with a history
      of IMT implantation for advanced geographic atrophy related to age-related
      macular degeneration developed an extrafoveal choroidal neovascular lesion. The
      patient underwent focal laser photocoagulation through the telescope without
      complication. Three months after treatment, no evidence of recurrence was noted,
      and visual acuity remained at 20/200. The IMT was not altered by the treatment.
      CONCLUSIONS: Focal thermal laser photocoagulation through an IMT can successfully
      treat choroidal neovascularization without damaging the device.

PMID- 16564825
TI  - Natural course of ocular function in pigmented paravenous retinochoroidal
      atrophy.
AB  - PURPOSE: To estimate mean rates of change of ocular function in patients with
      pigmented paravenous retinochoroidal atrophy (PPRCA). DESIGN: Retrospective
      observational case series. METHODS: Fifteen patients aged 8 to 67 years with
      PPRCA were followed for 3 to 35 years (average follow-up time, 13 years) with
      measures of visual acuity, visual field area, and full-field electroretinogram
      amplitude. Mean annual exponential rates of change were quantified by repeated
      measures longitudinal regression. RESULTS: Estimated mean annual rates of change
      were -2.0% for visual acuity, +0.3% for visual field area, and -3.4% and -6.7%
      for 0.5 Hz and 30 Hz electroretinogram amplitudes, respectively. CONCLUSION:
      Patients with PPRCA have a slowly progressive disease with respect to the loss of
      peripheral vision.

PMID- 16564827
TI  - Orbital cellulitis in a patient receiving infliximab for Ankylosing spondylitis.
AB  - PURPOSE: To describe a case of orbital cellulitis arising in a patient treated
      with an anti-TNFalpha agent. DESIGN: Single interventional case report. METHODS:
      A 42-year-old man developed severe unilateral orbital cellulitis while receiving
      infliximab (Remicade, Centocor) treatment for Ankylosing spondylitis (AS) as part
      of the open-label phase of a trial conducted at our tertiary referral center.
      Cultures grew Staphylococcus aureus. RESULTS: Infliximab treatment was stopped
      and the patient made a full recovery after receiving appropriate antibiotic
      therapy. Infliximab therapy was resumed after three weeks. CONCLUSIONS: Clinical
      vigilance is warranted when treating patients with anti-TNFalpha agents as these
      are associated with a diverse and growing number of ophthalmic complications.
      Resolved infection does not preclude the use of such agents.

PMID- 16564828
TI  - Nonprogressive extrafoveal retinal hole after foveal epiretinal membrane removal.
AB  - PURPOSE: To report an extrafoveal posterior retinal hole after surgical removal
      of foveal epiretinal membrane. DESIGN: Observational case reports. METHODS: We
      describe two patients who underwent vitrectomy surgery with an epiretinal
      membrane removal. Five months after vision improving surgery, a small retinal
      hole outside the macular area developed. RESULTS: Fundus photography and optical
      coherence tomography showed a full-thickness retinal hole with a surrounding cuff
      of subretinal fluid smaller than described in stage III or IV macular holes. The
      hole has been stable in shape and dimension, has not progressed to retinal
      detachment, and is not associated with an epiretinal membrane; the fluid is not
      impinging on the macular area. CONCLUSIONS: Asymptomatic full-thickness
      extrafoveal retinal holes, which do not progress to neurosensory detachment, can
      develop after epiretinal membrane peeling. These appear stable and have
      substantially smaller cuffs of subretinal fluid than typical macular holes.

PMID- 16564829
TI  - Treatment of herpes simplex virus stromal keratitis unresponsive to topical
      prednisolone 1% with topical cyclosporine 0.05%.
AB  - PURPOSE: To assess the efficacy of topical cyclosporine 0.05% (Restasis) in
      patients with herpes simplex virus nonnecrotizing stromal keratitis unresponsive
      to topical prednisolone. DESIGN: Prospective case series. METHODS: Patients with
      herpes simplex virus stromal keratitis (n = 12) that was unresponsive to topical
      prednisolone acetate 1% for at least four weeks were evaluated at a single site.
      Eyes were treated with topical cyclosporine twice a day and begun on a rapid
      prednisolone taper. Visual acuity, slit-lamp appearance, intraocular pressure,
      and corneal sensitivity were evaluated every two weeks for at least three months.
      RESULTS: Stromal keratitis resolved with cyclosporine in 10 of 12 patients after
      one month. The mean lesion area decreased more with cyclosporine than with
      prednisolone (2.0 mm with cyclosporine compared with 0.25 mm with prednisolone).
      After stopping cyclosporine therapy, four patients had recurrence of stromal
      keratitis. CONCLUSION: This series suggests that herpes simplex virus stromal
      keratitis can be treated effectively with topical cyclosporine, particularly in
      cases that are not responsive to topical prednisolone.

PMID- 16564830
TI  - Restrictive horizontal strabismus following blepharoplasty.
AB  - PURPOSE: To report a case of horizontal diplopia after a four-lid blepharoplasty.
      DESIGN: Observational and interventional case report. METHODS: Analysis of the
      history and management of a 64-year-old man who underwent a four-lid
      blepharoplasty, after which he developed horizontal diplopia. RESULTS: The
      patient was found to have a restrictive esotropia. He underwent a recession of
      the left medial rectus on an adjustable suture, with recurrence of the same
      pattern of diplopia one month after surgery. CONCLUSIONS: The involvement of the
      extraocular muscles as a complication of blepharoplasty is uncommon, but when it
      is present, it may be very difficult to treat.

PMID- 16564833
TI  - Intracameral Vigamox (moxifloxacin 0.5%) is not effective in preventing
      endophthalmitis in a rabbit model.

PMID- 16564831
TI  - Vitrectomy for macular holes associated with myopic foveoschisis.
AB  - PURPOSE: We reviewed the surgical results of vitrectomy for macular holes (MHs)
      associated with myopic foveoschisis (MF). DESIGN: Noncomparative, interventional
      case series. METHODS: setting: Institutional. participants: Eight eyes of eight
      patients with MHs associated with MF. intervention procedure: All patients
      underwent vitrectomy, internal limiting membrane peeling, and gas tamponade. main
      outcome measures: Slit-lamp-based biomicroscopy, optical coherence tomography
      examinations, and best-corrected visual acuity (BCVA) measurement. RESULTS: The
      MHs closed in two eyes (25%), and the BCVA improved more than 2 lines in three
      (37.5%) eyes, remained unchanged in three (37.5%), and worsened in two (25%). The
      MH size increased significantly in a case with an unresolved MH (P < .05). The
      postoperative BCVA was significantly correlated with the preoperative BCVA (P <
      .05). CONCLUSIONS: Although significant visual improvement occurs in less than
      50% of cases, vitrectomy can be beneficial for some cases.

PMID- 16564834
TI  - Comparative study of two sets of criteria for the diagnosis of Vogt-Koyanagi
      Harada disease.

PMID- 16564836
TI  - Evaluation of the cosmetic significance of external dacryocystorhinostomy scars.

PMID- 16564839
TI  - Inflow of ocular surface fluid into the anterior chamber after
      phacoemulsification through sutureless corneal cataract wounds.

PMID- 16564841
TI  - Chronic recurrent varicella-zoster virus keratitis confirmed by polymerase chain
      reaction testing.

PMID- 16564842
TI  - Severe fungal keratitis treated with subconjunctival fluconazole.

PMID- 16564844
TI  - Intravitreal plasmin injection activates endogenous matrix metalloproteinase-2 in
      rabbit and human vitreous.

PMID- 16564845
TI  - Intravitreal triamcinolone compared with macular laser grid photocoagulation for
      the treatment of cystoid macular edema.

PMID- 16564847
TI  - Intravitreal triamcinolone compared with macular laser grid photocoagulation for
      the treatment of cystoid macular edema.

PMID- 16564850
TI  - ASGE Technology Status Evaluation Report: wireless capsule endoscopy.

PMID- 16564851
TI  - ASGE guideline: colorectal cancer screening and surveillance.

PMID- 16564852
TI  - ASGE guideline: endoscopy in the diagnosis and treatment of inflammatory bowel
      disease.

PMID- 16564853
TI  - ASGE guideline: modifications in endoscopic practice for the elderly.

PMID- 16564854
TI  - ASGE guideline: the role of endoscopy in the surveillance of premalignant
      conditions of the upper GI tract.

PMID- 16564856
TI  - The colono-Barrett relationship: a tie that will not die.

PMID- 16564855
TI  - Colorectal neoplasia in veterans is associated with Barrett's esophagus but not
      with proton-pump inhibitor or aspirin/NSAID use.
AB  - BACKGROUND: It has been suggested that Barrett's esophagus (BE) is associated
      with an increased risk of developing colorectal neoplasia, but this has not been
      reported consistently. AIM: To study whether BE is associated with an increased
      risk of colorectal neoplasia, and if it is, whether it is dependent on use of
      proton-pump inhibitors (PPIs) or aspirin and nonsteroidal anti-inflammatory drugs
      (NSAIDs). DESIGN: Case-control study. SETTING: Endoscopic database of the Palo
      Alto Veterans Affairs Health Care System. POPULATION: 268 veterans with BE were
      matched with 268 controls without BE. INTERVENTION: Controls had undergone upper
      GI endoscopy within 14 days of the corresponding case. Colonoscopy was performed
      within 6 months in cases and controls. MAIN OUTCOME MEASURE: Development of
      colorectal neoplasia. RESULTS: Colorectal neoplasia was present in 162 of 268
      (60%) BE patients and in 105 of 268 (40%) controls (p < 0.001). The presence of
      BE (odds ratio [OR] 2.02: 95% CI [1.35, 3.04]), but also increasing age (OR 1.24
      per decade: 95% CI [1.04, 1.48]) and alcohol use (OR 1.70: 95% CI [1.16, 2.50])
      were associated with an increased risk of colorectal neoplasia in multivariable
      logistic regression analysis, whereas PPIs (OR 0.99: 95% CI [0.66, 1.48]) and
      aspirin/NSAIDs (OR 0.90: 95% CI [0.61, 1.33]) had no meaningful effect.
      LIMITATIONS: This was a retrospective study in mostly male veterans. CONCLUSIONS:
      Veterans with BE are at an increased risk of developing colorectal neoplasia.
      This association is independent from the use of PPIs or aspirin/NSAIDs.

PMID- 16564857
TI  - Evaluation of a new technique for endoscopic nasojejunal feeding-tube placement.
AB  - OBJECTIVES: Multiple techniques for endoscopic nasojejunal tube (NJT) placement
      exist. However, poor experience with these techniques has limited more routine
      practice of NJT placement for many endoscopists. We evaluated endoscopic NJT
      placement with a new stiff jejunal (J)-tube method (push technique). METHODS: The
      GI Tract database at the Medical University of South Carolina was queried for NJT
      placement procedures. Records of 42 patients who had undergone NJT placement by
      using the push technique between the years 2001 and 2004 at our institution were
      reviewed for information regarding procedure success and tube-related outcomes.
      RESULTS: The push technique of NJT placement was successful in 41 of 42 patients
      (97.6%), with an average procedure time of 11.6 minutes (range, 5-50 minutes).
      Negative outcomes occurred in 61% of properly positioned NJTs and included
      inadvertent tube removal by the patient or the staff (42.1%), dislodging (10.5%),
      clogging (5.3%), and kinking (5.3%). The average longevity of the NJT was 7.8
      days (range, 1-37 days). Most patients were ultimately converted to a
      percutaneous enteral access device or to oral feedings. CONCLUSIONS: Endoscopic
      placement of NJT by using the push technique is an efficient, reliable method of
      accessing the small bowel for enteral nutrition.

PMID- 16564858
TI  - Complete endoscopic closure of gastric perforation induced by endoscopic
      resection of early gastric cancer using endoclips can prevent surgery (with
      video).
AB  - BACKGROUND: When gastric perforation occurs during endoscopic resection for early
      gastric cancer, a surgical treatment generally is performed. Considering the
      increasing number of EMRs and the possibility of perforation, our research sought
      to investigate whether endoscopic treatment for gastric perforation is possible.
      METHODS: From 1987 to 2004, 121 of 2460 patients who underwent gastric EMR at the
      National Cancer Center Hospital had gastric perforation during EMR (4.9%). The
      initial 4 patients were treated with emergent surgery. The subsequent 117
      patients who were treated with endoclips formed our study population. RESULTS:
      Endoscopic closure with endoclips in 115 patients (98.3%) was successful. Two
      patients with unsuccessful endoscopic closure underwent emergent surgery. In the
      past 6 years, patients with perforation during gastric EMR treated with
      endoscopic closure had a recovery rate similar to that of the nonperforation
      cases. CONCLUSIONS: Gastric perforation during endoscopic resection can be
      conservatively treated by complete endoscopic closure with endoclips.

PMID- 16564859
TI  - Perforation: part and parcel of endoscopic resection?

PMID- 16564860
TI  - Validity of the Rockall scoring system after endoscopic therapy for bleeding
      peptic ulcer: a prospective cohort study.
AB  - BACKGROUND: The Rockall scoring system was developed in unselected patients, the
      majority of whom did not receive endoscopic therapy. The aim of this study was to
      assess the validity of the Rockall system in high-risk patients who undergo
      endoscopic therapy for peptic ulcer hemorrhage. METHODS: Rockall scores were
      calculated in 247 patients with major peptic ulcer bleeding entered into a
      randomized trial of endoscopic therapy. The observed rates of recurrent bleeding
      and mortality after endoscopic therapy were compared with predicted rates derived
      from Rockall's study group. The validity of the Rockall system was assessed in
      terms of calibration and discrimination. RESULTS: Rates of recurrent bleeding and
      mortality after endoscopic therapy increased with an increasing Rockall score.
      Observed rates of recurrent bleeding and mortality were below predicted rates,
      and calibration of the Rockall system was poor (Mantel-Haenszel chi square =
      25.8, p < 0.0001 for recurrent bleeding; Mantel-Haenszel chi square = 15.1, p <
      0.0001 for death). For the prediction of recurrent bleeding, the area under the
      receiver operating characteristic curve was low (63.4%), but the system was
      satisfactory when predicting mortality (area under the resulting curve, 84.3%).
      CONCLUSIONS: After endoscopic therapy for a bleeding peptic ulcer, the Rockall
      scoring system can identify patients at high risk of death, but it is inadequate
      for the prediction of recurrent bleeding.

PMID- 16564861
TI  - Rockall redux: retracted or redacted?

PMID- 16564862
TI  - 5F sphincterotomes and 4F sphincterotomes are equivalent for the selective
      cannulation of the common bile duct.
AB  - BACKGROUND: Cannulation of the common bile duct (CBD) is the first step in
      endoscopic retrograde cholangiopancreatography (ERCP). Cannulation difficulty is
      a known risk factor for post-ERCP complications and may be minimized by the use
      of a smaller caliber sphincterotome. OBJECTIVE: To compare the efficacy of CBD
      cannulation with a 4 F versus a 5 F sphincterotome. DESIGN: A randomized
      controlled trial, with concealed allocation and double-blinding. PATIENTS: Adult
      patients undergoing their first ERCP at a tertiary referral center. INTERVENTION:
      Patients were randomized to undergo CBD cannulation with either a 4 F or 5 F
      sphincterotome. MAIN OUTCOME MEASUREMENTS: Successful deep cannulation in <15
      attempts was the primary outcome. Secondary outcomes included number of
      attempts/time to cannulation, incidence of complications within 24 hours, and
      overall cannulation success (including patients before and after crossover).
      Analysis was intention to treat and included standard descriptive and inferential
      methods. RESULTS: A total of 107 patients were randomized: 51 (4 F) versus 56 (5
      F). The majority were female (71%) and white (92%). Baseline demographics,
      presenting symptoms, and laboratory values were similar between groups. Similar
      success in initial cannulation was observed: 84.3% (4 F) and 83.9% (5 F). No
      differences were noted in time to cannulation (5.12 min [SD, 4.8] for 4 F vs 4.46
      min [SD, 4.13] for 5 F; p = NS), number of attempts to cannulation (6.2 [SD, 5.2]
      for 4 F vs 5.7 [SD, 4.9] for 5 F; p = NS), or complications. The overall
      cannulation success was 92.2% (4 F) and 92.9% (5 F). LIMITATIONS: Premature
      termination of the trial resulted in decreased power. CONCLUSIONS: There exists
      no significant difference in efficacy between 4 F and 5 F sphincterotomes. The
      choice of initial sphincterotome should be dictated by physician preference.

PMID- 16564863
TI  - Frequency of major complications after EUS-guided FNA of solid pancreatic masses:
      a prospective evaluation.
AB  - BACKGROUND: EUS-guided FNA is effective for establishing tissue diagnosis in
      suspected pancreatic cancer. However, data on the frequency of major
      complications following EUS-FNA are limited. OBJECTIVE: To evaluate the frequency
      of major complications after EUS-FNA of solid pancreatic masses. DESIGN:
      Prospective cohort study. SETTING: Tertiary University based referral center for
      pancreatico-biliary disorder. PATIENTS: Consecutive patients who underwent EUS
      FNA of a solid pancreatic over a 42-month period. All immediate complications
      were recorded by the endosonographer. Late complications were assessed at 72
      hours and at 30-days after the procedure. MAIN OUTCOMES MEASUREMENTS: Major
      complications were defined as acute pancreatitis, bleeding, infection,
      perforation, use of reversal medication, hospitalization or death. RESULTS: A
      total of 355 consecutive patients with a solid pancreatic mass underwent EUS FNA.
      Major complications were encountered in 9 patients (2.54%, 95% CI 1.17-4.76).
      Acute pancreatitis occurred in 3 of 355 (0.85 %, 95% CI 0.17-2.45); 2 patients
      were hospitalized, and 1 patient recovered with outpatient analgesics. Three
      patients were admitted for severe pain after the procedure; all were treated with
      analgesics and subsequently discharged with no sequela. Two patients (0.56%, 95%
      CI 0.07-2.02) developed fever and were admitted for intravenous antibiotics; 1
      patient recovered with intravenous antibiotics and the other required surgical
      debridement for necrosis. One patient required the use of reversal medication.
      Overall, 1.97% (95% CI 0.80-4.02) of the patients were hospitalized for
      complications (range 1-16 days). None of the patients experienced clinically
      significant hemorrhage, perforation, or death. No clear predisposing risk factors
      were identified. LIMITATIONS: Lack of surgical gold standard and referral to a
      tertiary center. CONCLUSIONS: EUS-FNA of solid pancreatic masses infrequently
      leads to major complications. Our results can be used by endosonographers to
      counsel patients before EUS-FNA of solid pancreatic masses.

PMID- 16564864
TI  - Know when to biopsy 'em, know when to walk away.

PMID- 16564865
TI  - Endoscopic drainage of pancreatic-fluid collections in 116 patients: a comparison
      of etiologies, drainage techniques, and outcomes.
AB  - BACKGROUND: Pancreatic-fluid collections are frequent sequelae of acute and
      chronic pancreatitis, and endoscopic drainage of these collections has gained
      acceptance as an alternative to surgical drainage. METHODS: Patient data,
      collection characteristics, drainage technique, and outcomes were obtained
      through chart review and prospective follow-up for 116 patients with attempted
      endoscopic drainage of symptomatic pancreatic-fluid collections. RESULTS: A total
      of 116 patients presented with fluid collections classified as acute fluid
      collection (n = 5), necrosis (n = 8), acute pseudocyst (n = 30), chronic
      pseudocyst (n = 64), and pancreatic abscess (n = 9). The median diameter of the
      collection drained was 60 mm (15-275 mm). Median follow-up after drainage was 21
      months. The drainage technique was transpapillary in 15 patients, transmural in
      60, and both in 41. Successful resolution of symptoms and collection occurred in
      87.9% of cases. No difference in success rates was observed between patients with
      acute pancreatitis and those with chronic pancreatitis. However, drainage of
      organized necrosis was associated with a significantly higher failure rate than
      other collections. No significant differences were observed regarding success
      when disease, drainage technique, or site of drainage was considered.
      Complications occurred in 13 patients (11%), and there were 6 deaths in the 30
      days after drainage, including one that was procedure related. CONCLUSIONS:
      Endoscopic drainage of pancreatic-fluid collections is successful in the majority
      of patients and is accompanied by an acceptable complication rate.

PMID- 16564866
TI  - Endoscopic therapy for pancreatic-fluid collections: lessons for success?

PMID- 16564867
TI  - Determination of qualitative telomerase activity as an adjunct to the diagnosis
      of pancreatic adenocarcinoma by EUS-guided fine-needle aspiration.
AB  - BACKGROUND: Telomerase activity is up-regulated in pancreatic cancer. Hence,
      measurement of telomerase activity in pancreatic needle-biopsy specimens could
      assist in establishing a positive diagnosis in specimens that are inadequate for
      cytology. OBJECTIVE: To determine the sensitivity and specificity of telomerase
      activity for neoplasia in a series of EUS-guided fine-needle aspirate (EUS-FNA)
      biopsies of pancreatic mass lesions. DESIGN: Prospective, consecutive, non
      randomized cohort. SETTING: Academic hospital, tertiary referral center.
      PATIENTS: Seventy-one patients with a pancreatic mass diagnosed by cross
      sectional imaging. INTERVENTIONS: EUS-FNA of 52 solid and 18 cystic pancreatic
      lesions. MAIN OUTCOME MEASUREMENTS: (1) Cytologic diagnosis; (2) tissue
      telomerase activity by semi-quantitative polymerase chain reaction; (3) patient
      demographics; (4) clinical outcomes. RESULTS: Cytology results were positive for
      adenocarcinoma in 40 patients with a solid pancreatic mass; of these, telomerase
      activity was detected in 31. There were no telomerase false-positive results.
      Telomerase results were positive in 6 of the 7 patients (86%) who had negative
      cytology results and who eventually were found to have biopsy-proven
      adenocarcinoma. The sensitivity and specificity of telomerase activity for
      detecting pancreatic adenocarcinoma in solid masses was 79% (95% CI, 64%-89%) and
      100% (95% CI, 55%-100%). LIMITATIONS: Extremely high sensitivity and specificity
      of EUS-FNA cytology in solid lesions minimized the incremental benefit of
      telomerase. CONCLUSIONS: Telomerase activity can be measured readily in specimens
      obtained at EUS-FNA and accurately predicts malignancy. Used in combination with
      cytology, telomerase increased the sensitivity from 85% to 98% while maintaining
      the specificity at 100%. Lesions with negative cytology result and positive
      telomerase activity should be evaluated aggressively to exclude malignancy.

PMID- 16564868
TI  - The role of ERCP in patients with pancreatico-biliary problems in the setting of
      hematopoietic stem cell transplant.
AB  - BACKGROUND: Patients undergoing hematopoietic stem cell transplant may develop
      pancreatico-biliary complications that may require ERCP. Due to their
      immunocompromised state, these patients may be at higher risk of procedure
      related complications. OBJECTIVE: To determine the role of ERCP in the diagnosis
      and treatment of patients who have undergone hematopoietic stem cell transplant
      and the patients' clinical outcomes. DESIGN: Retrospective analysis of patients
      with hematopoietic stem cell transplant who underwent ERCP from 1997 to 2004
      evaluating ERCP indications, diagnosis, therapeutic interventions, and
      complications. SETTING: Tertiary referral center. RESULTS: Of the 16 patients
      identified, 9 were female, 15 had had allogeneic hematopoietic stem cell
      transplant, and 1 had an autologous hematopoietic stem cell transplant. Twenty
      six ERCP procedures were performed in the 16 patients. Index ERCP findings
      included: extra hepatic bile duct obstruction in 12 patients, of which 7 had
      biliary lithiasis. Ampullary obstruction due to infiltration from graft versus
      host disease was seen in 3 of 12 patients, benign bile duct stricture in 1 of 12,
      and ampullary obstruction in the setting of a peri-ampullary diverticulum in 1 of
      12. Index ERCP findings in the remaining 4 patients included: intrahepatic bile
      duct compression due to metastatic disease in 1 of 16 patients, bile duct leak in
      1 of 16, pancreatic duct stone in 1 of 16, and normal ERCP in 1 of 16.
      Complications occurred in 4 patients: mild pancreatitis (1), mild bleeding (1),
      cholangitis due to late stent occlusion (1), and intermittent bradycardia (1).
      There were no ERCP-related deaths. LIMITATIONS: Single-center study. CONCLUSION:
      In patients with hematopoietic stem cell transplant, bile duct lithiasis was the
      most common finding at ERCP, followed by obstructive ampullary tissue
      infiltration due to graft versus host disease. ERCP yielded clinically relevant
      information in this particular group of patients.

PMID- 16564870
TI  - Introducer method of percutaneous endoscopic cecostomy and antegrade continence
      enema by use of the Chait Trapdoor cecostomy catheter in patients with adult
      neurogenic bowel.
AB  - BACKGROUND: Previous reports on percutaneous endoscopic cecostomy (PEC) for the
      delivery of antegrade continence enema (ACE) in adults have been presented in the
      form of case reports. Heretofore the tubes used in the pull method of PEC have
      been thick bolster catheters. The author performed PEC by using the introducer
      method (IM) with 10 F Chait Trapdoor cecostomy catheters (CTCC) in adult cases.
      OBJECTIVE: Report author experience with a new method of PEC in adults. DESIGN:
      Case series. SETTING: Single institution in Japan. PATIENTS: Five patients with
      bowel obstruction and 15 patients with chronic severe constipation.
      INTERVENTIONS: The interventions were the pull method or IM of PEC and drainage
      or ACE. In 5 cases, PEC was performed by the pull method with the use of an 18 F
      to 24 F bolster catheter for decompression of dilated intestine. In 15 patients
      with chronic constipation, PEC was performed with the IM method using a balloon
      catheter (11 F or 15 F) and CTCC. ACE was performed every other day. RESULTS: PEC
      was successful and effective (decompression and evacuation) in all patients. In
      patients with IM of PEC, 5 patients were placed with a 15 F balloon catheter and
      10 patients were placed with an 11 F balloon catheter. Immediate bleeding
      occurred in 1 case. Balloon rupture occurred during the first month or on average
      at the 1 month period. Nine of 10 patients who had the 11 F catheters were
      changed to CTCC. The advantages of CTCC were prevention of accidental balloon
      rupture, decreased leakage and granulation tissue, and ease of exchange compared
      with bolster catheter. LIMITATIONS: Retrospective, single-institution.
      CONCLUSIONS: PEC with IM is a safe and useful method. CTCC is advantageous on a
      long-term basis for ACE.

PMID- 16564871
TI  - Third-tier fellowship training in hepatology: advantages and program selection.

PMID- 16564869
TI  - The yield of wireless capsule endoscopy in the detection of neuroendocrine tumors
      in comparison with CT enteroclysis.
AB  - BACKGROUND: Patients with neuroendocrine tumors (NET) of the small bowel often
      present with metastatic disease, and localization of the primary tumor still is a
      diagnostic challenge. Wireless capsule endoscopy (WCE) is an established method
      that improves the diagnostic evaluation of diseases of the small intestine.
      OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of WCE
      in imaging neuroendocrine tumors of the small bowel in these patients. DESIGN: We
      retrospectively compared the findings of capsule endoscopy to the findings of CT
      enteroclysis in patients with histopathological confirmation of NET. PATIENTS:
      Eight patients with newly established diagnosis of metastatic NET were included.
      INTERVENTIONS: All patients underwent CT enteroclysis and wireless capsule
      endoscopy within a maximum of 2 weeks. MAIN OUTCOME MEASUREMENTS: Number of
      primary tumors detected. The results of surgery were used as a gold standard for
      both methods. RESULTS: CT enteroclysis detected the primary tumor in 4 of 8
      patients whereas WCE found the primary in 3 patients. On the contrary, CT
      enteroclysis provided more false-positive results. LIMITATIONS: Frequent
      extraluminal tumor growth. CONCLUSIONS: In patients with NET, wireless capsule
      endoscopy may be helpful in individual cases but the general diagnostic value of
      this method may be limited due to frequent extraluminal growth of these tumors.

PMID- 16564872
TI  - Endoscopic plication of massively bleeding peptic ulcer by using the Eagle Claw
      VII device: a feasibility study in a porcine model.
AB  - BACKGROUND AND OBJECTIVE: We examined the efficacy of endoscopic plication when
      using Eagle Claw VII in a porcine bleeding ulcer model. ANIMAL MODEL PREPARATION:
      The right gastroepiploic artery (diameter 1.5-2 mm) was isolated and was tunneled
      to small gastrotomies at either the lesser or greater curvature of the stomach.
      INTERVENTIONS: We applied the Eagle Claw VII to achieve hemostasis. MAIN OUTCOME
      MEASUREMENTS: The survival of the pigs after endoscopic plication for hemostasis,
      time to achieve hemostasis with Eagle Claw VII, recurrent bleeding, number of
      successful plication, and number of suture remained. RESULTS: Endoscopic
      plication was performed on bleeding gastric ulcers in 6 pigs. The time to achieve
      hemostasis was 6 minutes 56 seconds +/- 3 minutes 50 seconds. There was no
      complication. A total of 14 plications were performed. All animals survived for 1
      week without recurrent bleeding. At the postmortem, 10 of the plication sutures
      remained. LIMITATION: Our model cannot simulate the chronicity of peptic ulcer.
      CONCLUSIONS: In this porcine model, the Eagle Claw VII effectively stopped
      bleeding from arteries 2 mm in size.

PMID- 16564873
TI  - Parallel cannulation technique at ERCP rendezvous.
AB  - BACKGROUND: Biliary access at ERCP rendezvous is usually achieved by withdrawing
      a wire passed antegrade via the accessory channel of the duodenoscope, which is
      then used for over-the-wire cannulation. The wire is time consuming to maneuver
      and may be damaged during withdrawal. OBJECTIVE: Description of a simple
      technique for cannulation at rendezvous that overcomes these problems. DESIGN:
      Observational study. SETTING: Gastroenterology department of a teaching district
      general hospital. PATIENTS: Fourteen consecutive patients undergoing rendezvous
      after percutaneous transhepatic cholangiography (PTC). INTERVENTION: A
      transpapillary drain was placed at PTC in 13 patients. At rendezvous, cannulation
      alongside the drain was attempted with a sphincterotome cannula. After successful
      cannulation, the drain was progressively withdrawn, allowing retrograde
      therapeutic intervention. RESULTS: In all 13 patients, parallel cannulation was
      successful, allowing stone removal or biliary stent placement, with cannulation
      alongside a guidewire in the fourteenth patient. There were no complications
      except right hypochondrial pain after drain removal. CONCLUSIONS: Parallel
      cannulation is straightforward and effective, avoiding the need for guidewire
      manipulation.

PMID- 16564874
TI  - Wire-guided pancreatic pseudocyst drainage by using a modified needle knife and
      therapeutic echoendoscope.
AB  - BACKGROUND: Various methods to drain pancreatic pseudocysts by using EUS guidance
      have been reported in the literature. OBJECTIVE: A new drainage technique is
      described that uses a modified needle knife advanced over a guidewire positioned
      in the pseudocyst by EUS guidance. DESIGN: Retrospective chart review. SETTING:
      Academic medical center. PATIENTS: Consecutive subjects from December 1, 2002, to
      January 10, 2005, with symptomatic pseudocysts in whom EUS-guided drainage was
      attempted. INTERVENTIONS: By using a therapeutic linear echoendoscope, a 19-gauge
      aspiration needle was inserted into the pseudocyst. A guidewire was placed
      through the needle, and a needle knife with the cutting wire protruding and bent
      was advanced over the guidewire to contact the stomach mucosa. The needle knife
      was then advanced by using electrocautery into the pseudocyst. The
      cystenterostomy was dilated by using a balloon over the guidewire. One to 4
      stents were placed through the tract. MAIN OUTCOME MEASUREMENTS: Successful
      pseudocyst drainage. RESULTS: A total of 21 of 23 patients underwent technically
      successful pseudocyst drainage. One patient had self-limited hypotension during
      the procedure. Another patient had free intraperitoneal air after the procedure
      but correct stent placement. LIMITATIONS: Retrospective analysis, small sample
      size. CONCLUSIONS: In this preliminary experience, wire-guided pseudocyst
      drainage with a modified needle knife appears effective and safe while allowing
      for a more controlled pseudocyst puncture.

PMID- 16564875
TI  - Peroral transgastric organ resection: a feasibility study in pigs.
AB  - BACKGROUND: The feasibility of peroral transgastric peritoneoscopy, liver biopsy,
      and tubal ligation has been demonstrated in prior animal studies. This approach
      has the potential to reduce postoperative morbidity. OBJECTIVE: To explore the
      technical challenges and complications of performing a transgastric organ
      resection. DESIGN: Two-week animal survival study. INTERVENTIONS: Five female
      Yorkshire pigs underwent peroral transgastric partial hysterectomy. With the
      animals under general anesthesia, a sterile esophageal overtube was placed and a
      gastric antibiotic lavage was performed. Subsequently, a needle-knife and through
      the-scope dilating balloon were used to make an anterior gastric wall incision
      through which a therapeutic gastroscope was advanced into the peritoneal cavity.
      Endoscopes and instruments previously had been disinfected in a 2.4%
      glutaraldehyde bath or were disposable. An endoloop and polypectomy snare were
      used to resect a portion of the uterus, which was removed through the mouth.
      Gastric incision closure was attempted with endoclips. After 2 weeks of
      observation, necropsy was performed. RESULTS: Transgastric partial hysterectomy
      was performed on all 5 animals. One animal became lethargic and febrile, so
      necropsy was performed on day 4. An incompletely closed gastric incision and
      suppurative peritonitis were found. A second animal developed a fever; necropsy
      performed on day 14 revealed a gastric abscess at the incision site and scattered
      abdominal pus. No complications were encountered in the 3 remaining animals, and
      necropsy revealed well-healed gastric incisions and no evidence of peritonitis.
      CONCLUSION: Endoscopic transgastric partial hysterectomy is technically feasible
      in a porcine model. Strict sterility seems mandatory but cannot always be
      assured. Incomplete closure of the gastric incision may lead to significant
      complications.

PMID- 16564876
TI  - Transgastric surgery: avoiding pitfalls in the development of a new technique.

PMID- 16564877
TI  - Aneurysmal artery within a gastric ulcer.

PMID- 16564878
TI  - Meckel's diverticulum bleeding detected by capsule endoscopy.

PMID- 16564879
TI  - EUS-assisted EMR of a large duodenal carcinoid tumor.

PMID- 16564880
TI  - Identifying obscure appendiceal polyps: the "deflated lumen" technique.

PMID- 16564881
TI  - Virtual colonoscopy in the evaluation of a pararectal cavitary lesion after
      hysterectomy.

PMID- 16564882
TI  - Mycophenolate mofetil-associated enterocolitis.

PMID- 16564883
TI  - Endoscopic diagnosis and removal of Ascaris lumbricoides during colonoscopy for
      polyp surveillance (with video).

PMID- 16564884
TI  - Endoscopic repair of gastric leaks after Roux-en-Y gastric bypass: a less
      invasive approach.
AB  - BACKGROUND: Gastric leaks represent an important source of morbidity and
      mortality associated with Roux-en-Y gastric bypass. These leaks, once managed
      acutely, can become chronic and represent a difficult clinical challenge.
      Surgical options to address a chronic gastric leak are technically challenging
      and often unsuccessful. We present a novel peroral endoscopic treatment for
      patients with chronic gastric leaks after Roux-en-Y gastric bypass. DESIGN: Case
      series. INTERVENTIONS: Repair of chronic gastric leaks after Roux-en-Y gastric
      bypass by using a combination of argon plasma coagulation, hemoclips, fibrin
      glue, Polyflex stent placement, and distal gastrojejunal stenosis dilation. The
      goal was to achieve durable fistula closure and avoid surgery. MAIN OUTCOME
      MEASUREMENTS: Durable fistula closure as assessed by an upper-GI series and
      clinical evaluation. RESULTS: Gastric leak closure was achieved in all 3
      patients, with complete resolution of symptoms. Polyflex stent migration into the
      Roux limb occurred in 1 patient, and this was retrieved endoscopically. There
      were no other significant complications. CONCLUSIONS: Peroral endoscopic repair
      of gastric leaks is technically feasible. This procedure may offer a less
      invasive alternative to traditional surgical revision.

PMID- 16564886
TI  - Severe upper-GI bleed caused by gastritis cystica profunda.

PMID- 16564885
TI  - Postendoscopic sphincterotomy hemobezoar (with video).

PMID- 16564887
TI  - Massive gastric ulceration after transarterial chemoembolization for
      hepatocellular carcinoma.

PMID- 16564888
TI  - Successful treatment of intrahepatic biloma by combined percutaneous and
      endoscopic technique: an intrabiloma "rendezvous".

PMID- 16564889
TI  - Mesenteric torsion causing small-bowel obstruction as a complication of
      colonoscopy.

PMID- 16564890
TI  - Successful endoscopic closure of a lateral duodenal perforation at ERCP with
      fibrin glue.

PMID- 16564891
TI  - Treatment of benign complete colonic anastomotic obstruction by using an
      endoscopic rendezvous technique.

PMID- 16564892
TI  - Cholesterol embolism after colonoscopy: a case report.

PMID- 16564893
TI  - Response.

PMID- 16564894
TI  - Argon plasma coagulation of Dieulafoy's lesions.

PMID- 16564895
TI  - Exercising caution during placement of wireless pH monitoring capsule.

PMID- 16564896
TI  - Pneumatic dilation of achalasia cardia under direct endoscopy: the debate
      continues.

PMID- 16564897
TI  - Glue for gastric varices: why are we so reluctant in the United States?

PMID- 16564898
TI  - Influence of chemotherapy administration on the occurrence of peri-PEG abdominal
      wall metastases.

PMID- 16564900
TI  - Hookworm infection: does it cause overt intestinal bleeding?

PMID- 16564901
TI  - Endoscopic papillectomy is not attempted just because it is feasible.

PMID- 16564903
TI  - Solitary rectal ulcer: another view of the management algorithm.

PMID- 16564905
TI  - Measuring the quality of endoscopy.

PMID- 16564906
TI  - Quality indicators for gastrointestinal endoscopic procedures: an introduction.

PMID- 16564907
TI  - Quality indicators for esophagogastroduodenoscopy.

PMID- 16564908
TI  - Quality indicators for colonoscopy.

PMID- 16564909
TI  - Quality indicators for endoscopic retrograde cholangiopancreatography.

PMID- 16564910
TI  - Quality indicators for endoscopic ultrasonography.

PMID- 16564911
TI  - The comparative pathology of severe acute respiratory syndrome and avian
      influenza A subtype H5N1--a review.
AB  - The pathology of 2 zoonotic human viral infections that recently emerged, severe
      acute respiratory syndrome (SARS) due to coronavirus (SARS-CoV) and avian
      influenza A subtype H5N1, is reviewed and compared based on the literature and
      the cases examined by the authors. Pneumocytes are the primary target of
      infection resulting in diffuse alveolar damage. Systemic cytokine activation
      results in hemophagocytic syndrome, lymphoid depletion, and skeletal muscle fiber
      necrosis. Severe acute respiratory syndrome induces a more fibrocellular intra
      alveolar organization with a "bronchiolitis obliterans organizing pneumonia"-like
      pattern and presence of multinucleated histiocytes and pneumocytes. H5N1 causes a
      more fulminant and necrotizing diffuse alveolar damage with patchy and
      interstitial paucicellular fibrosis. Severe acute respiratory syndrome associated
      coronavirus persists in the lung up to the second month, whereas H5N1 persists in
      the lung up to the third week. Severe acute respiratory syndrome associated
      coronavirus disseminates to blood, urine, feces, gastrointestinal tract, and
      liver. There is recent report of possible cerebral involvement by H5N1 and its
      isolation in the blood, gastrointestinal tract, and cerebrospinal fluid. More
      pathologic studies are urgently needed.

PMID- 16564912
TI  - Prognostic significance of microvessel density and vascular endothelial growth
      factor expression in sinonasal carcinomas.
AB  - The prognostic significance of microvessel density and proliferative activity of
      the neoplastic cells, evaluated respectively by CD31 and Ki-67 positivity, and
      immunohistochemical expression of vascular endothelial growth factor (VEGF) was
      retrospectively investigated in 105 cases of sinonasal carcinoma (80 surgical
      specimens and 25 biopsies). The most represented histologic types were intestinal
      type adenocarcinoma found in 36 patients (34.3%), squamous cell carcinoma (SCC)
      in 34 (32.4%), mucinous adenocarcinoma (mainly made up of signet-ring cell
      patterns) in 15 (14.3%), and adenoid cystic carcinoma in 7 (6.7%). Microvessel
      density values (in vessels per square millimeter), VEGF, and Ki-67 were not
      dependent on histologic type but were rather correlated to the histologic grading
      in SCC. Clinical data were available for 92 (87.6%) of 105 patients, with minimum
      follow-up of 48 months. Most of the patients (81.5%) were at an advanced stage
      (T3-T4) at diagnosis. The values of all markers were correlated to tumor stage (P
      = .03). Multivariate analysis showed that both microvessel density and
      proliferative activity of the neoplastic cells were independent prognostic
      parameters (mortality hazard ratio, 1.33 and 1.60, respectively). Although VEGF
      expression was not correlated to prognosis on the whole series (P = .06), it was
      a powerful prognostic marker when the analysis was restricted to the group of
      SCCs (hazard ratio, 3.02; 90% confidence interval, 1.58-5.80). These results show
      that tumor neoangiogenesis, expressed by microvessel density, together with
      proliferative activity, is a pathologic marker with a strong prognostic impact in
      sinonasal carcinomas. Therefore, it may be a useful tool in this field so as to
      carry out therapeutic protocol planning, which may be further enhanced by the
      adoption of the more recent antiangiogenic molecules.

PMID- 16564913
TI  - Fatty acid synthase gene overexpression and copy number gain in prostate
      adenocarcinoma.
AB  - Cancer cells frequently exhibit a significant increase in overexpression and
      activity of fatty acid synthase (FASN). Elevated FASN pathway activity also
      occurs in prostate cancer, the second leading cause of cancer-related death in
      men in the United States. Studies show that genes associated with an increase in
      protein expression, such as HER2/neu in breast cancer, are associated with an
      increase in gene copy number as well as an increase in transcription. In the
      present study, we evaluated whether FASN follows a similar paradigm in prostate
      cancer. To date, elevated FASN expression in prostate cancer has not been
      correlated with gene copy number alterations. Using immunohistochemistry and
      fluorescence in situ hybridization analysis in paraffin-embedded tissue
      microarrays, we observed gene copy gain in 24% of all prostate adenocarcinoma
      specimens examined with concurrent increased FASN protein expression.
      Immunohistochemistry alone showed 59% of prostate cancer specimens in the same
      tissue microarray with high FASN expression. Increased FASN gene was observed in
      53% of all prostate tissues expressing elevated FASN protein levels and in 2 of 5
      prostate tumor cell lines tested. These findings suggest that FASN gene copy
      number increases may be involved in the resultant increase in FASN protein
      expression observed in prostatic disease.

PMID- 16564914
TI  - Epidermal growth factor receptor expression and gene copy number in fibrolamellar
      hepatocellular carcinoma.
AB  - Increased expression of epidermal growth factor receptor (EGFR), a transmembrane
      tyrosine kinase, is associated with tumor progression in many carcinomas.
      Epidermal growth factor receptor inhibitors have shown promise in treating some
      of these tumors. Fibrolamellar hepatocellular carcinoma (FL-HCC) is an aggressive
      neoplasm that occurs in young patients with no history of cirrhosis. This study
      examines the expression and gene copy number of EGFR in FL-HCC. Formalin-fixed,
      paraffin-embedded FL-HCC (n = 13) sections were stained with a monoclonal
      antibody against EGFR. Fluorescence in situ hybridization analysis was performed
      using probes against EGFR gene and centromeric region of chromosome 7 (CEP 7).
      Epidermal growth factor receptor and CEP 7 signals were counted in 50 tumor
      nuclei per case as well as 300 normal hepatocyte nuclei. The EGFR to CEP 7 signal
      ratio was calculated for each case. Most (92%, 12/13) of FL-HCC showed strong and
      diffuse staining with anti-EGFR antibody. Fluorescence in situ hybridization was
      informative in 11 cases, 10 of which showed extra EGFR gene copy numbers (mean,
      3.69; range, 3.13-5.0). Epidermal growth factor receptor was overexpressed in all
      these cases. The mean number of EGFR signals per cell in FL-HCC was double that
      of normal hepatocytes (3.69 versus 1.80); the mean EGFR/CEP 7 ratio in tumor
      cells was 1.05. In conclusion, EGFR is strongly overexpressed on the cell
      membrane in nearly all cases of FL-HCC. Similar gains of chromosome 7 are
      observed, indicating that the extra EGFR gene copies are due to polysomy rather
      than gene amplification. The strong expression of EGFR in FL-HCC tumors suggests
      that they may respond to treatment with EGFR antagonists.

PMID- 16564915
TI  - Prognostic value of HER2 expression in meningiomas: an immunohistochemical and
      fluorescence in situ hybridization study.
AB  - The aggressiveness of meningiomas is unpredictable. HER2 represents a well-known
      prognostic factor in various tumors such as breast carcinomas. This work was
      designed to study HER2 protein expression and HER2 gene amplification in
      meningiomas and to evaluate their prognostic value. Frozen sections of 35
      meningiomas were immunostained for HER2, estrogen receptor, progesterone
      receptor, E-cadherin, and MIB-1. Meningiomas immunostained for HER2 were further
      examined for the HER2 gene amplification by dual-color fluorescence in situ
      hybridization using probes for centromere 17 and 17q11.2-q12. Complete clinical
      information was obtained in all cases. The study included 15 atypical
      meningiomas, 3 anaplastic meningiomas, and 17 classic meningiomas. Five
      atypical/anaplastic meningiomas and 5 classic meningiomas of the whole 35 (28.5%)
      meningiomas expressed HER2 protein. This was considered as an overexpression in
      comparison with negative normal meninges. Fluorescence in situ hybridization
      demonstrated more HER2 gene copy in 4 of these 10 HER2-positive meningiomas. At
      equivalent histologic grading, meningiomas with HER2 overexpression exhibited
      similar immunohistochemical parameters of prognostic value than their HER2
      negative counterparts; however, the rate of tumor recurrence was significantly
      higher in meningiomas with HER2 overexpression than in HER2-negative meningiomas.
      Conversely, HER2 amplification was not associated with recurrence. Some
      meningiomas exhibit HER2 protein overexpression in part induced by gene
      amplification. However, only HER2 overexpression could represent an independent
      prognostic factor in meningiomas.

PMID- 16564916
TI  - Matrix metalloproteinases and matrix metalloproteinase inhibitors in acute lung
      injury.
AB  - The objective of this study was to assess matrix metalloproteinase (MMP) and MMP
      inhibitor expression in the airspace of patients with acute lung injury (ALI) or
      acute respiratory distress syndrome (ARDS) and to determine the prognostic
      significance of MMP expression in this patient population. Twenty-eight patients
      with ALI or ARDS were prospectively enrolled in this study; bronchoalveolar
      lavage (BAL) fluid obtained from these patients was examined for expression of
      MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin-1),
      MMP-8 (neutrophil collagenase), and MMP-9 (gelatinase B). Levels of MMP
      inhibitors (ie, tissue inhibitor of metalloproteinases-1 and -2 [TIMP-1 and TIMP
      2]) were examined in parallel. Expression of MMPs was correlated with relevant
      clinical outcomes in patients with ALI/ARDS. In nearly all specimens obtained
      from patients with ALI/ARDS, there were high levels of MMP-2, MMP-8, MMP-9, and
      TIMP-1, but in only a small subset of patients (6/28) were there detectable
      levels of MMP-1 and/or MMP-3. In the patients with elevated MMP-1 and/or MMP-3,
      the mortality rate was higher (83%) than in the group without detectable levels
      of these enzymes (32%). Likewise, the overall severity of disease as indicated by
      Acute Physiology and Chronic Health Evaluation III scores was higher in this
      group (98 +/- 30) than in the group without detectable MMP-1 or MMP-3 (78 +/-
      28). The percentage of individuals in whom lung disease was complicated by
      multiorgan failure was also higher in the group with detectable MMP-1 and/or MMP
      3 (83%) than in the group without (64%), as was the number of organs that failed.
      In contrast, there was no correlation between MMP-1 and/or MMP-3 expression and
      impairment in gas exchange, as determined by the ratio of partial pressure of
      oxygen to fraction of inspired oxygen (Pao(2)/Fio(2)) on the day of BAL sample.
      Based on these findings, we conclude that elevated MMP-2, MMP-8, and MMP-9 in BAL
      fluid is a marker of acute lung injury (and, perhaps, a contributor to ALI) but
      is not necessarily an indicator of a poor outcome. On the other hand, the
      presence of detectable MMP-1 and/or MMP-3 is an indicator of more ominous disease
      progression.

PMID- 16564917
TI  - High Twist expression is involved in infiltrative endometrial cancer and affects
      patient survival.
AB  - Epithelial-mesenchymal transition (EMT) is critical not only for morphogenesis
      during embryonic development but also the conversion of early-stage tumors into
      infiltrative phenotypes. The present study examines the expression of Twist, a
      highly conserved bHLH transcription factor that is known to promote EMT, and
      evaluated its prognostic significance in endometrial cancers. Tissue specimens
      from 70 patients with endometrial cancer who underwent primary surgery were
      immunohistochemically evaluated for Twist expression. A semiquantitative scoring
      system was developed based on the intensity and extent of cancer cells with Twist
      expression. Thirty-six patients (51%) exhibited high Twist expression and 34
      (49%) had low expression. Most cases exhibited both cytoplasmic and nuclear
      staining mainly observed in cancer foci and, preferentially, at the margin but,
      in some cases, the stromal cells located adjacent to cancer foci as well. Among
      various clinical variables, high Twist expression was significantly associated
      with deep myometrial invasion (>1/2) (P = .012) and concurrent with decreased E
      cadherin expression (P < .001), a hallmark of EMT. In univariate survival
      analyses, both myometrial invasion and Twist expression influenced overall
      survival, but Cox multivariate analyses revealed that only Twist was an
      independent predictor of patient survival (hazard ratio, 5.12; P = .023). Thus,
      our data implies that high Twist expression is a potential novel prognostic
      factor for disease survival of endometrial cancer. Furthermore, the present study
      implicates Twist as a potential therapeutic target for this tumor type.

PMID- 16564918
TI  - Immunohistochemical detection of histidine decarboxylase in neoplastic mast cells
      in patients with systemic mastocytosis.
AB  - Synthesis of histamine in hematopoietic progenitor cells may be one of the
      earliest events in mastopoiesis. We therefore asked whether the key enzyme
      involved in histamine production, histidine decarboxylase (HDC), can be used as
      an immunohistochemical marker for the detection of immature neoplastic mast cells
      (MC) in patients with MC-proliferative disorders. To address this question, we
      examined bone marrow biopsy specimens in a cohort of 102 patients with
      mastocytosis using an antibody against HDC. Independent of the maturation stage
      of MC, the anti-HDC antibody produced clear diagnostic staining results in all
      patients with systemic MC disease examined including those with MC leukemia and
      MC sarcoma, in which MCs are particularly immature. In these patients, expression
      of HDC was reconfirmed at the messenger RNA level by reverse transcriptase
      polymerase chain reaction analyses performed with RNA of highly enriched CD117(+)
      MC. In summary, HDC is expressed in neoplastic MC in patients with systemic
      mastocytosis independent of the maturation stage of cells or the variant of
      disease. Histidine decarboxylase should therefore be considered as a new MC
      marker in the screen panel of antigens used to diagnose high-grade MC
      malignancies.

PMID- 16564919
TI  - Loss of Ku70/Ku80 expression occurs more frequently in hereditary than in
      sporadic colorectal tumors. Tissue microarray study.
AB  - Ku70 and Ku80 proteins take part in the repairing of DNA double-strand breaks by
      their function as a regulatory subunit of the DNA-dependent protein kinase. In
      this study, expression of both genes was analyzed in colorectal carcinoma tissue
      arrays applying immunohistochemistry. Expression of both genes decreased along
      with pT stage. Significant differences in Ku70 and Ku80 expression were found
      between pT3 and pT4 as well as between pT2 and pT3 tumors, respectively. Loss of
      Ku70/Ku80 expression was more frequently observed in hereditary than in sporadic
      tumors. We conclude that expression of Ku70/Ku80 genes is down-regulated in
      colorectal carcinoma and that defects of these genes are more frequently observed
      in hereditary than in sporadic tumors.

PMID- 16564920
TI  - High epidermal growth factor receptor amplification rate but low mutation
      frequency in Middle East lung cancer population.
AB  - Epidermal growth factor receptor (EGFR) exon 18-21 mutations were shown to be
      highly predictive of response to gefitinib (Iressa) therapy in lung cancer.
      Studies on Western and Japanese lung cancers have indicated substantial
      differences in the EGFR mutation frequency between these populations. To
      investigate the prevalence of EGFR in another distinct ethnic group, EGFR
      alterations were studied in 47 consecutive non small cell lung cancers from Saudi
      Arabia by immunohistochemistry, fluorescence in situ hybridization, and DNA
      sequencing. Detectable EGFR expression was seen in 69.8% of 43 interpretable
      cancers. Epidermal growth factor receptor amplification, present in 15.3% of 39
      analyzable cancers, was strongly associated with high levels of EGFR expression
      (P = .0047). Only 1 exon 18-21 mutation was seen among 34 lung cancers that could
      be successfully sequenced. It is concluded that EGFR exon 18-21 mutations are
      rare in Middle East patients with lung cancer and occur in a similar range as in
      Western patients. The remarkable high rate of EGFR gene amplifications could
      potentially facilitate studies on the predictive role of gene copy number changes
      for response to anti-EGFR therapies in Middle East patient sets.

PMID- 16564921
TI  - The association between intratubular seminoma and invasive germ cell tumors.
AB  - Intratubular seminoma (ITS) has been defined as the complete filling of the
      seminiferous tubules with seminoma cells with no Sertoli cells present. This
      contrasts with intratubular germ cell neoplasia, unclassified (IGCNU), where the
      malignant germ cells are interspersed by Sertoli cells. We aimed to determine the
      relationship between these 2 entities and the association between ITS and
      invasive classic seminomas. We therefore examined the morphology and
      immunochemistry of ITS and IGCNU adjacent to germ cell tumors to differentiate
      the patterns, frequency, and distribution of these lesions. We found that ITS was
      seen in equal frequency adjacent to seminomas as it was to nonseminomas. The
      presence of ITS in non-seminomatous germ cell tumors suggests that it is a true
      in situ lesion rather than representative of intratubular spread of an existing
      seminoma. However, because it is not specifically associated with seminoma, we
      suggest that it is not useful to discriminate this lesion from IGCNU and that it
      merely represents an advanced form of IGCNU on the way to invasive malignancy.

PMID- 16564922
TI  - Expression of S-100 protein in renal cell neoplasms.
AB  - Polyclonal antibody to S-100 protein has been routinely applied for initial
      screening of various types of tumors, including, melanocytic tumors and
      neurogenic tumors. S-100 protein has been shown to have a broad distribution in
      human tissues, including renal tubules. The potential utility of S-100 protein in
      renal cell neoplasms has not been extensively investigated. Using an EnVision
      Horseradish Peroxidase (HRP; Dako, Carpinteria, Calif) kit, we evaluated the
      diagnostic value of S-100 protein on tissue microarray sections from 175 cases of
      renal epithelial neoplasm (145 primary renal neoplasms and 30 metastatic renal
      cell carcinomas) and 24 non-neoplastic renal tissues. Immunohistochemical stains
      for pancytokeratin, HMB-45, and Mart-1 were also performed. Western blot using
      the same antibody (anti-S-100 protein) was performed on 10 cases of renal cell
      neoplasm. The results demonstrated that nuclear and cytoplasmic staining pattern
      for S-100 protein was observed in 56 (69%) of 81 conventional (clear cell) renal
      cell carcinomas (RCCs), 10 (30%) of 33 papillary RCCs, 1 (6%) of 16 ChRCCs, and
      13 (87%) of 15 oncocytomas. Among the 81 cases of CRCC, positivity for S-100
      protein was seen in 41 (71%) of 58 and 15 (65%) of 23 cases with Furhman nuclear
      grade I/II and III/IV, respectively. Focal immunostaining was present in 22 (92%)
      of 24 normal renal tubules. Similar staining pattern was observed in 21 (70%) of
      30 metastatic RCCs. Western blotting demonstrated the S-100 protein expression in
      both renal cell neoplasm and normal renal tissue. Overexpression of S-100 in
      oncocytomas compared with ChRCCs was confirmed by the data of Western blot and
      cDNA microarray analysis. Importantly, 14.8% (12/81) of clear cell RCC and 13.3%
      (4/30) of metastatic RCC revealed an immunostaining profile of pancytokeratin (
      )/S-100 protein (+). These data indicate that caution should be taken in
      interpreting an unknown primary with S-100 positivity and cytokeratin negativity.
      In addition, it suggests that S-100 has a diagnostic value in differentiating
      oncocytoma from ChRCC.

PMID- 16564923
TI  - Cyclooxygenase-2 overexpression associated with a poor prognosis in
      chondrosarcomas.
AB  - Recent studies have shown increased levels of cyclooxygenase (COX)-2 in various
      human malignancies, including some bone and soft tissue tumors, but little is
      known about the presence of COX-2 in chondrosarcomas. We performed
      immunohistochemical staining for COX-2 in 74 chondrosarcomas and compared the
      staining results with the characteristics and outcome of the patients. Thirty
      seven men and 37 women between the ages of 14 and 81 years (median, 50 years)
      participated in the study. The tumors were located in the axial skeleton in 47
      cases and in the long bones in 27 cases. The largest diameters of the tumors
      ranged from 2.7 to 32 cm (median, 8.0 cm). The immunohistochemistry findings
      revealed the overexpression of COX-2 in 16 (22%) of the 74 patients. Thirteen
      (41%) of 32 grade 2 and 2 (67%) of 3 grade 3 chondrosarcomas showed
      overexpression for COX-2, whereas only 1 (3%) of 39 grade 1 chondrosarcomas
      showed overexpression. Overexpression of COX-2 was significantly associated with
      histologic grade (P < .001) and a decreased disease-specific survival (P < .001).
      These findings suggest that COX-2 overexpression in chondrosarcoma is a negative
      prognostic factor that may be strongly associated with histologic grade.

PMID- 16564924
TI  - Extragonadal germ cell tumors are often associated with Klinefelter syndrome.
AB  - Klinefelter syndrome is a well documented abnormality of sex differentiation,
      with an incidence of 1 in 600 newborn males. It is characterized by a 47,XXY or a
      mosaic karyotype and clinical findings of hypergonadotrophic hypogonadism, small
      testes, infertility, reduced body hair, gynecomastia, and tall stature. Other
      conditions like venous disease, autoimmune disorders, mild neurobehavioral
      deficit, diabetes mellitus, sexual precocity, and osteoporosis may also affect
      these patients. Different malignancies such as breast cancer, testicular tumors,
      leukemia, and lymphomas occur in 1%-2% of the cases. Klinefelter syndrome has
      been associated with other malignancies such as extragonadal germ cell tumors;
      however, some authors consider this association an unusual finding. We report the
      molecular cytogenetic studies performed in 4 young males with mediastinal germ
      cell tumors. In 2 cases, a 47,XXY karyotype was recognized in different tissues
      by fluorescent in situ hybridization, whereas the other 2 had a normal XY
      karyotype. We propose that in young patients with mediastinal teratoma, a
      cytogenetic analysis must always be performed.

PMID- 16564925
TI  - De novo concurrent papillary renal cell carcinoma and angiomyolipoma in a kidney
      allograft: evidence of donor origin.
AB  - In the general population, renal cell carcinoma (RCC) is a relatively common
      neoplasm; however, the papillary RCC subtype is infrequent and represents only 10
      to 15% of all RCC. Angiomyolipoma is a well-known common benign tumor. The
      occurrence of RCC in association with angiomyolipoma is a rare event, with only
      approximately 50 cases reported in the nontransplantation setting. In transplant
      recipients, RCC can develop in native kidneys, but its occurrence "de novo" in
      the renal allograft is very rare with an estimated incidence of less than 0.5%.
      We report here the case of a 39-year-old woman who underwent cadaveric renal
      transplantation in 1990. No lesion was observed in the allograft during the pre-
      and perioperative period or on early postoperative ultrasounds. No graft
      rejection occurred under a standard triple immunosuppressive therapy. Thirteen
      years later, during a routine ultrasonography, 2 solid masses were discovered in
      the allograft, both of them richly vascularized. She underwent allograft
      nephrectomy and the histologic findings revealed that one of the tumors was a
      chromophilic (type 1) papillary RCC (2.5 cm in diameter) and the other, an
      angiomyolipoma (1.5 cm). Microsatellite analysis of the allograft, as compared
      with the recipient peripheral blood leukocytes, demonstrated that the 2 tumors (1
      malignant and 1 benign) were of donor origin. To our knowledge, this is the first
      report of de novo concurrent papillary RCC and angiomyolipoma in a renal
      allograft.

PMID- 16564926
TI  - Case report: central neurocytoma with concomitant cerebral involvement by acute
      lymphatic leukemia.
AB  - Central neurocytomas are intraventricular tumors composed of round uniform cells.
      These tumors have usually favorable prognosis. Leukemic infiltrates are
      occasionally seen as a complication of acute lymphatic leukemia. This report
      describes a 7-year-old boy who was treated because of diagnosed lymphatic
      leukemia with central nervous system involvement and concomitant neurocytic tumor
      located in the fourth ventricle. These two entities might be problematic to
      differentiate from each other without proper histopathological examination.

PMID- 16564927
TI  - A case of multifocal fibrosclerosis with intracardiac solid masses.
AB  - We report an extremely rare case of multifocal fibrosclerosis (MFS) with
      intracardiac solid masses. A 70-year-old woman with Hashimoto's disease had
      pericardial thickening and intracardiac masses. Histology of pericardiectomy
      showed only fibrosis. The clinical diagnosis was constrictive pericarditis. She
      died of postoperative infectious mediastinitis and cerebral infarction.
      Postmortem examination revealed intracardiac solid masses contiguous to thickened
      pericardium. Multifocal areas of fibrosis were also seen in the pericardium,
      mediastinum, abdominal cavity, and the retroperitoneum. The intracardiac masses
      and the areas of fibrosis were composed of collagenous fibers with various
      intensities of inflammatory infiltrates and sclerotic changes. Neoplastic changes
      were not observed. These histological features were similar to that of MFS. The
      intracardiac masses are interpreted as one of the manifestations of MFS. This is
      the first case of MFS accompanied with intracardiac solid masses.

PMID- 16564928
TI  - Estrogen receptor beta--which one and where should we draw the line?

PMID- 16564930
TI  - Myeloproliferative disorders carrying the t(8;9) (PCM1-JAK2) translocation.

PMID- 16564932
TI  - Fulminant pulmonary calciphylaxis and metastatic calcification causing acute
      respiratory failure in a uremic patient.
AB  - Calciphylaxis is a rare and life-threatening disorder characterized by small
      vessel mural calcification with intimal proliferation, fibrosis, and thrombosis,
      resulting in tissue ischemic necrosis. Although it has been viewed as a systemic
      disease involving mainly the dermis, subcutaneous fat, or muscle, calciphylaxis
      of other organs rarely is reported. We describe the case of a 25-year-old uremic
      woman who rapidly developed massive pulmonary calcification that led to acute
      respiratory failure after the initiation of hemodialysis therapy. Chest
      radiography and high-resolution computed tomography showed typical pulmonary
      calcification. Pulmonary calciphylaxis and metastatic calcification were
      confirmed further by lung tissue biopsy. No skin or muscle calciphylaxis was
      discovered. Despite multiple factors precipitating pulmonary calciphylaxis in
      this patient, we speculate that hemodialysis was the main culprit in accelerating
      the development of fulminant pulmonary calciphylaxis and metastatic
      calcification. Alteration in the local environment from an acid to an alkaline
      condition and a relatively high dialysate calcium level in the presence of
      systemic hyperphosphatemia are believed to have facilitated the deposition of
      calcification. This case highlights the importance of "visceral calciphylaxis"
      and early identification of its causes.

PMID- 16564933
TI  - Lymphoid interstitial lung disease in a patient with acute tubulointerstitial
      nephritis and uveitis: a new facet of a rare syndrome?
AB  - We report for the first time the appearance of lymphoid interstitial lung disease
      in a patient with tubulointerstitial nephritis and uveitis (TINU) syndrome. A 41
      year-old woman with a 9-month history of recurrent bilateral iridocyclitis was
      referred to our division for examination of renal dysfunction. Renal biopsy
      showed extensive interstitial CD3+ lymphocytic infiltration; glomerular
      structures were unaffected. After oral corticosteroid therapy, renal function
      remained stable during the next few years. Uveitis was controlled by using
      topical steroids. Five years after first presentation, the patient developed
      symptoms suggestive of interstitial lung disease, combined with a relapse of
      uveitis. Lung biopsy showed lymphofollicular bronchiolitis (CD3+) associated with
      florid alveolitis. There was no evidence for acute infection or systemic disease
      to be the cause of this pathological state. Lung disease proved to be steroid
      responsive. A new pulmonary flare-up 3 years later responded to renewed
      treatment. Accounting for the histological findings, we assume both TINU syndrome
      and interstitial lung disease to be manifestations of a common autoimmune
      disorder.

PMID- 16564934
TI  - A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study
      of AST-120 (Kremezin) in patients with moderate to severe CKD.
AB  - BACKGROUND: AST-120 (Kremezin; Kureha Chemical Industry Co Ltd, Tokyo, Japan) is
      an orally administered adsorbent showing adsorption ability superior to activated
      charcoal for certain organic compounds known to be precursors of substances that
      accumulate in patients with chronic kidney disease (CKD) and that are believed to
      accelerate the decline in kidney function. AST-120 is approved in Japan for
      prolonging time to hemodialysis therapy and improving uremic symptoms in patients
      with CKD. METHODS: A multicenter, randomized, double-blind, placebo-controlled,
      dose-ranging study was designed to examine the nephroprotective effects of 3
      doses of AST-120 versus placebo in adult patients with moderate to severe CKD and
      elevated serum indoxyl sulfate levels while following an adequate protein-intake
      diet. Eligible patients were randomly assigned to 1 of 3 doses of AST-120 (0.9,
      2.1, or 3.0 g) or placebo 3 times daily for 12 weeks. RESULTS: AST-120 decreased
      serum indoxyl sulfate levels in a dose-dependent fashion. During the 12-week
      treatment period, AST-120 did not affect serum creatinine levels or 24-hour urine
      creatinine appearance. Significant improvements in malaise were observed in a
      dose-dependent fashion. All doses of AST-120 were well tolerated and did not
      adversely affect the general health status of patients. CONCLUSION: Results
      suggest that the dose of 3 g 3 times daily is an optimal dose for the US
      population, and it may be useful in the treatment of patients with CKD. Because
      AST-120 did not directly affect serum creatinine levels or 24-hour urine
      creatinine appearance, the composite end point of doubling of serum creatinine
      level, transplantation, and dialysis therapy would be appropriate for a
      confirmatory phase III therapeutic outcome study.

PMID- 16564935
TI  - mRNA expression of target genes in the urinary sediment as a noninvasive
      prognostic indicator of CKD.
AB  - BACKGROUND: Study of messenger RNA (mRNA) expression of target genes in urinary
      sediment was suggested as a noninvasive marker of renal damage in patients with
      chronic kidney diseases (CKDs). We studied the relationship between urinary mRNA
      expression of target genes and risk for renal function deterioration in patients
      with CKD. METHODS: We studied 131 patients with CKD with kidney biopsy. mRNA
      expression of 11 target genes in urinary sediment was measured by means of
      quantitative polymerase chain reaction. Patients then were followed up for 27.4
      +/- 10.1 months. The primary end point is doubling of serum creatinine
      concentration or end-stage renal disease. RESULTS: Thirty-six patients (27.5%)
      reached the primary end point during follow-up. Univariate analysis showed that
      sex, age, proteinuria, estimated glomerular filtration rate, histological
      diagnosis, degree of tubulointerstitial scarring, percentage of
      glomerulosclerosis, and urinary mRNA expression of hepatocyte growth factor (HGF)
      were predictors of the primary end point. At 24 months, event-free survival rates
      were 90.9% and 64.3% for patients with low and high urinary HGF expression,
      respectively (log rank test, P = 0.002). After adjusting for other confounding
      factors by using a Cox proportional hazard model, urinary HGF expression remained
      an independent predictor of the primary end point, and a 1-fold increase in
      expression was associated with a 4.0% (95% confidence interval, 0.5 to 7.5; P =
      0.024) increase in risk. CONCLUSION: In the target genes examined, urinary HGF
      expression is an independent prognostic indicator of CKD after adjusting for
      confounding clinical and histological factors. Measurement of urinary HGF mRNA
      expression may be a useful noninvasive tool for risk stratification of patients
      with CKD.

PMID- 16564936
TI  - Tissue Doppler imaging in the evaluation of left ventricular function in young
      adults with autosomal dominant polycystic kidney disease.
AB  - BACKGROUND: Hypertension and increased left ventricular mass index (LVMI) have
      been reported in patients with early stages of autosomal dominant polycystic
      kidney disease (ADPKD). Whether these abnormalities are associated with diastolic
      dysfunction in this stage remains to be established. The aim of the study is to
      evaluate diastolic function in young normotensive patients with ADPKD by using
      tissue Doppler imaging (TDI), the most sensitive method available to date.
      METHODS: Thirty-two young clinically normotensive patients aged 21 to 30 years
      were compared with 23 controls with similar ages. Ambulatory blood pressure
      measurement (ABPM) was performed to confirm normal blood pressure. Subsequently,
      patients and controls underwent echocardiography using transmitral Doppler and
      TDI. RESULTS: LVMI was greater in patients with ADPKD than controls (89.3 +/-
      17.7 versus 77.6 +/- 15.9 g/m2; P < 0.02). No significant differences were found
      in transmitral Doppler and TDI results. When ABPMs were taken into account, 11
      patients had mild hypertension and showed increased LVMI and decreased early
      diastolic peak velocity (E wave: 67.0 +/- 12.0 cm/s in hypertensive patients with
      ADPKD versus 81.4 +/- 3.3 cm/s in normotensive patients with ADPKD versus 79.3 +/
      2.9 cm/s in controls; P < 0.04) and decreased TDI peak early diastolic annular
      velocity (11.6 +/- 2.8 cm/s in hypertensive patients with ADPKD versus 13.2 +/-
      1.6 cm/s in normotensive patients with ADPKD versus 13.4 +/- 1.6 in controls; P <
      0.05). CONCLUSION: Diastolic dysfunction is not a prominent sign in young
      normotensive patients with ADPKD.

PMID- 16564937
TI  - Use of beta-blockers and aspirin after myocardial infarction by patient renal
      function in the Department of Defense health care system.
AB  - BACKGROUND: Whether the previously reported underutilization of standard-of-care
      medications in the management of patients with acute myocardial infarction (AMI)
      persists in more recent years or differs by ward of admission has not been
      reported. METHODS: We performed a retrospective cross-sectional study of patients
      hospitalized with a discharge diagnosis of incident AMI to a Department of
      Defense hospital (Walter Reed Army Medical Center, Washington, DC) from 2001
      through 2004. Use of beta-blockers and aspirin at the time of discharge after AMI
      was assessed according to Modification of Diet in Renal Disease (MDRD) estimated
      glomerular filtration rate (eGFR) in milliliters per minute per 1.73 m2,
      stratified by admission to the coronary care unit (CCU) versus other wards.
      Adjusted odds ratios for discharge beta-blocker and aspirin therapy were
      calculated by using logistic regression. RESULTS: Among 431 patients, overall
      discharge use of beta-blockers was 86.8%, and aspirin, 86.8%, both significantly
      greater after CCU admission than admission to other wards (93%, aspirin use;
      91.7%, beta-blocker use; P < 0.001 and P < 0.001). In logistic regression, CCU
      admission was the only independent factor associated with either beta-blocker or
      aspirin use; MDRD eGFR was not associated significantly with beta-blocker and
      aspirin use regardless of admission to the CCU or non-CCU. CONCLUSION: Future
      studies of disparities in use of standard-of-care medications after AMI according
      to renal function should account for the primary site of admission, particularly
      CCU versus others. In addition, legitimate contraindications to the use of beta
      blockers and aspirin may be subtle, including appropriate end-of-life decisions.

PMID- 16564938
TI  - Population prevalence of albuminuria in the Australian Diabetes, Obesity, and
      Lifestyle (AusDiab) study: immunonephelometry compared with high-performance
      liquid chromatography.
AB  - BACKGROUND: Microalbuminuria is an independent risk factor for cardiovascular
      morbidity and mortality in the general population. Standard immunochemical
      urinary albumin assays detect immunoreactive albumin, whereas high-performance
      liquid chromatography (HPLC) detects both immunoreactive and immunounreactive
      albumin. METHODS: Using data from the Australian Diabetes, Obesity, and Lifestyle
      cohort study of randomly selected community-based Australian adults, spot urine
      samples were tested for albuminuria (spot urine albumin-creatinine ratio [ACR]:
      normal, < 30 mg/g; microalbuminuria, 30 to 300 mg/g; and macroalbuminuria, > 300
      mg/g) by using both immunonephelometry (IN) and HPLC (n = 10,010). RESULTS: Bland
      Altman analysis showed significant bias, with a greater ACR by means of HPLC,
      particularly at lower levels of ACR. Mean ACR was 15.8 mg/g (95% confidence
      interval [CI], 12.3 to 19.2) by means of IN compared with 30.0 mg/g (95% CI, 27.0
      to 35.0) by means of HPLC. The prevalence of microalbuminuria was 4 times greater
      by means of HPLC compared with IN (20% versus 5.5%). In all demographic and
      comorbid subgroups associated with microalbuminuria, the prevalence of
      microalbuminuria increased by 2 to 4 times. A total of 1,743 subjects (17.4%)
      classified as normoalbuminuric by means of IN were reclassified as
      microalbuminuric by means of HPLC. Using multivariate logistic regression, women,
      patients with untreated and treated hypertension, and those with impaired glucose
      tolerance or diabetes were associated significantly with a change in category
      from normoalbuminuric to microalbuminuria by means of HPLC. CONCLUSION: HPLC
      measures significantly more urinary albumin within the normoalbuminuria and
      microalbuminuria range, resulting in a significant increase in prevalence of
      microalbuminuria. Longitudinal studies are needed to determine whether the extra
      individuals identified by means of HPLC are at increased risk for developing hard
      clinical outcomes (renal and cardiovascular).

PMID- 16564939
TI  - Hemodialysis timing, survival, and cardiovascular outcomes in the Hemodialysis
      (HEMO) Study.
AB  - BACKGROUND: The timing of medical therapies has been shown to influence the
      outcomes and side effects of treatments for disease. This report examines the
      extent to which hemodialysis treatment time of day was associated with
      cardiovascular mortality and morbidity and all-cause mortality in a secondary
      analysis of the Hemodialysis Study. METHODS: Dialysis start time defined dialysis
      shift: morning beginning between 0400 and 0930 hours (n = 822); midday, between
      0930 and 1530 hours (n = 851); and evening, between 1530 and 2200 hours (n =
      172). Outcome measures included all-cause mortality, cardiac death, composite end
      point of all-cause mortality or first cardiac hospitalization, and composite end
      point of first cardiac hospitalization or cardiac death. RESULTS: Morning
      hemodialysis was associated with a lower likelihood of cardiovascular events
      compared with the evening shift in all-cause mortality or first cardiac
      hospitalization (evening versus morning, relative risk [RR], 1.29; 95% confidence
      interval [CI], 1.01 to 1.65; P = 0.043), as well as first cardiac hospitalization
      or cardiac death (evening versus morning, RR, 1.44; 95% CI, 1.11 to 1.89; P =
      0.007). No differences were noted in the other 2 outcomes, and there was no
      statistically significant difference between the morning and midday shifts.
      Although crude mortality rates were greater in the midday compared with morning
      (RR, 1.21; 95% CI, 1.05 to 1.39; P = 0.008), this association was attenuated
      after adjustment (RR, 1.04; 95% CI, 0.89 to 1.22; P = 0.64). CONCLUSION: Making
      extensive adjustment for patient characteristics, this report does not support
      the association of lower all-cause mortality with morning hemodialysis or a
      particular benefit for older patients.

PMID- 16564941
TI  - The effect of glucose added to the dialysis fluid on blood pressure, blood
      glucose, and quality of life in hemodialysis patients: a placebo-controlled
      crossover study.
AB  - BACKGROUND: Risk for hypoglycemia increases during hemodialysis sessions. The
      compensatory homeostatic response to hypoglycemia may increase the risk for
      abnormal blood pressure regulation. The purpose is to determine blood pressure
      and blood glucose levels and variability in these variables during dialysis with
      and without glucose in the dialysis fluid. METHODS: In a randomized, placebo
      controlled, unblinded, crossover study of 44 hemodialysis patients, 34 patients
      without diabetes and 10 patients with diabetes were allocated to treatment with
      and without glucose in the dialysis fluid during two 10-week periods. Blood
      pressure and blood glucose levels were determined 5 to 8 times at each dialysis
      session during both periods. Quality of life was estimated by using the 36-Item
      Short-Form Health Survey questionnaire at the end of both treatment periods.
      RESULTS: With glucose in the dialysis fluid, blood pressure was significantly
      lower (systolic, 144 +/- 20 versus 149 +/- 21 mm Hg; P < 0.003; diastolic, 73 +/-
      10 versus 76 +/- 10 mm Hg; P < 0.001), blood glucose level was higher (125 +/- 25
      versus 110 +/- 26 mg/dL [6.96 +/- 1.36 versus 6.08 +/- 1.47 mmol/L]; P < 0.001),
      and quality of life was the same. Variations in systolic and diastolic blood
      pressures and blood glucose levels were the same during both treatments. In the
      subgroup of patients with diabetes, variation in blood glucose levels decreased
      significantly with glucose in the dialysis fluid (mean, 30 versus 37 mg/dL [1.66
      versus 2.03 mmol/L]; P = 0.008). CONCLUSION: Systolic and diastolic blood
      pressures decreased with glucose in the dialysis fluid in patients with chronic
      renal failure, presumably because of insulin-induced vasodilatation in patients
      without diabetes. Blood glucose level regulation improved in the diabetic
      subgroup, and blood glucose levels were not greater in patients with diabetes
      with glucose in the dialysis water. Quality of life was not changed.

PMID- 16564940
TI  - A randomized crossover trial comparing sevelamer with calcium acetate in children
      with CKD.
AB  - BACKGROUND: A multicenter, randomized, open-label, crossover study was performed
      to compare the efficacy and safety of sevelamer, a calcium-free phosphate binder,
      with calcium acetate in pediatric patients with chronic kidney disease (CKD).
      METHODS: Children (age, 0.9 to 18 years) with CKD undergoing hemodialysis or
      peritoneal dialysis or with a glomerular filtration rate of 20 or greater and
      less than 60 mL/min/1.73 m2 (> or = 0.33 and < 1.00 mL/s/1.73 m2) were randomly
      assigned to the following treatment scheme: 2 weeks of washout followed by 8
      weeks of treatment with either sevelamer or calcium acetate in a crossover
      fashion. Phosphorus, calcium, and intact parathyroid hormone in serum were
      measured every 2 weeks, and phosphate binder dosages were adjusted, if needed.
      Serum lipid and vitamin concentrations were measured at the beginning and end of
      each treatment period. The primary end point was the decrease in serum phosphorus
      levels after 8 weeks of treatment. RESULTS: Forty-four patients were screened.
      Altogether, data for 18 patients (5 girls) aged 12.4 +/- 4.1 years were used for
      the crossover analysis. There was no significant difference in serum phosphorus
      levels at 8 weeks after the start of treatment in both groups. Total cholesterol
      (-27%) and low-density lipoprotein cholesterol (-34%) levels decreased
      significantly with sevelamer treatment (P < 0.02 and P < 0.005). An increased
      incidence of hypercalcemia (P < 0.0005) was observed with calcium acetate
      treatment, whereas metabolic acidosis was more frequent with sevelamer treatment
      (P < 0.005). CONCLUSION: Treatment of children with CKD with sevelamer and
      calcium acetate provides similar phosphorus level control. The marked decrease in
      lipid levels and lower rate of hypercalcemia may augment the long-term benefit of
      sevelamer.

PMID- 16564942
TI  - Effect of intravenous ascorbic acid in hemodialysis patients with EPO
      hyporesponsive anemia and hyperferritinemia.
AB  - BACKGROUND: Although erythropoietin (EPO)-hyporesponsive anemia in hemodialysis
      patients most commonly results from iron deficiency, the contributory role of
      chronic inflammation and oxidative stress in its pathogenesis is poorly
      understood. We conducted an open-label prospective study to assess the effect of
      vitamin C, an antioxidant, on EPO-hyporesponsive anemia in hemodialysis patients
      with unexplained hyperferritinemia. METHODS: Forty-six of 262 patients in an
      inner-city hemodialysis center met the inclusion criteria (administration of
      intravenous iron and EPO for > or = 6 months at a dose > or = 450 U/kg/wk,
      average 3-month hemoglobin [Hb] level < or = 11.0 g/dL [< or = 110 g/L], ferritin
      level > or = 500 ng/mL (microg/L), and transferrin saturation [TSAT] < or = 50%).
      Patients were excluded if they had a clear explanation for the EPO
      hyporesponsiveness. Four patients refused to participate. The remaining patients
      were randomly assigned; 20 patients to receive standard care and 300 mg of
      intravenous vitamin C with each dialysis session (group 1) and 22 patients to
      receive standard care only (group 2). Study duration was 6 months. During the
      study, 1 patient from group 1 was removed (upper gastrointestinal bleeding) from
      final analysis. Monthly assessment included Hb level, mean corpuscular volume,
      iron level, iron-binding capacity, ferritin level, TSAT, and Hb content in
      reticulocytes. In addition, biointact parathyroid hormone, aluminum, C-reactive
      protein (CRP), and liver enzymes were measured every 3 months. RESULTS: Age, sex,
      race, and time on dialysis therapy were similar in both groups. At 6 months, Hb
      levels significantly increased from 9.3 to 10.5 g/dL (93.0 to 105.0 g/L) in group
      1, but not group 2 (9.3 to 9.6 g/dL [93.0 to 96.0 g/L]; P = 0.0001). Similarly,
      TSAT increased from 28.9% to 37.3% in group 1, but not group 2 (28.7% to 29.3%; P
      = 0.0001). EPO dose (477 to 429 versus 474 to 447 U/kg/wk), iron-binding capacity
      (216 to 194 versus 218 to 257 microg/dL [38.7 to 34.7 versus 39 to 46
      micromol/L]), and CRP level (2.8 to 0.9 versus 2.8 to 2.2 mg/dL) decreased
      significantly in group 1, but not in controls. Changes in Hb content in
      reticulocytes and ferritin level also were statistically significant in group 1.
      There was no change in biointact parathyroid hormone levels. Although serum iron
      levels and intravenous iron doses changed within each group, changes were equal
      between the 2 groups. CONCLUSION: In hemodialysis patients with refractory anemia
      and hyperferritinemia, vitamin C improved responsiveness to EPO, either by
      augmenting iron mobilization from its tissue stores or through antioxidant
      effects.

PMID- 16564943
TI  - Chronic insomnia in kidney transplant recipients.
AB  - BACKGROUND: Recent studies confirmed that sleep disorders have a significant
      impact on various aspects of health in patients at different stages of chronic
      kidney disease. At the same time, there is an almost complete lack of information
      on the prevalence and correlates of insomnia in kidney transplant recipients.
      METHODS: In a cross-sectional study, the Athens Insomnia Scale was used to assess
      the prevalence of insomnia in a large sample of kidney transplant recipients
      compared with wait-listed dialysis patients and also a matched group obtained
      from a nationally representative sample of the Hungarian population. RESULTS: The
      prevalence of insomnia was 15% in wait-listed patients, whereas it was only 8% in
      transplant recipients (P < 0.001), which, in turn, was not different from the
      prevalence of this sleep problem in the sample of the general population (8%).
      Prevalences of insomnia in the transplant group were 5%, 7%, and 14% for the
      groups with glomerular filtration rates (GFRs) greater than 60 mL/min (> 1.00
      mL/s), 30 to 60 mL/min (0.50 to 1.00 mL/s), and less than 30 mL/min (< 0.5 mL/s),
      respectively (P < 0.01). However, estimated GFR was no longer associated
      significantly with insomnia in the transplant population after statistical
      adjustment for several covariates. In a multivariate model, insomnia was
      significantly and independently associated with treatment modality
      (transplantation versus wait listing), as well as the presence of depression,
      restless legs syndrome, and high risk for obstructive sleep apnea syndrome, and
      with self-reported comorbidity. CONCLUSION: The prevalence of insomnia was
      substantially less in the transplant group than in wait-listed dialysis patients
      and similar to that observed in the general population. Because this condition
      potentially is treatable, attention should be directed to the appropriate
      diagnosis and management of insomnia in the kidney transplant recipient
      population.

PMID- 16564944
TI  - Understanding the basic case-mix adjustment for the composite rate.
AB  - In April 2005, Medicare began adjusting payments to dialysis providers for
      composite-rate services for a limited set of patient characteristics, including
      age, body surface area, and low body mass index. We present analyses intended to
      help the end-stage renal disease community understand the empirical reasons
      behind the new composite-rate basic case-mix adjustment. The U-shaped
      relationship between age and composite-rate cost that is reflected in the basic
      case-mix adjustment has generated significant discussion within the end-stage
      renal disease community. Whereas greater costs among older patients are
      consistent with conventional wisdom, greater costs among younger patients are
      caused in part by more skipped sessions and a greater incidence of certain costly
      comorbidities. Longer treatment times for patients with a greater body surface
      area combined with the largely fixed cost structure of dialysis facilities
      explains much of the greater cost for larger patients. The basic case-mix
      adjustment reflects an initial and partial adjustment for the cost of providing
      composite-rate services.

PMID- 16564945
TI  - Marked recovery of severe renal lesions in POEMS syndrome with high-dose
      melphalan therapy supported by autologous blood stem cell transplantation.
AB  - POEMS syndrome is a rare plasma cell disorder, characterized by polyneuropathy,
      organomegaly, endocrinopathy, serum monoclonal protein, and skin lesions.
      Although not included in the acronym, renal lesions also are characteristic of
      this disease and sometimes require dialysis therapy. We treated a 61-year-old
      woman with POEMS syndrome with high-dose melphalan therapy (HDT) supported by
      autologous blood stem cell transplantation (SCT), and clinical remission was
      achieved. A repeated renal biopsy showed the striking effectiveness of this
      therapy on renal lesions. Pathological features of the renal lesions, such as
      membranoproliferative glomerulonephritis-like lesions, microangiopathic
      glomerulopathy, and mesangiolytic lesions with microcapillaries, almost
      completely disappeared. This treatment also markedly decreased serum levels of
      vascular endothelial growth factor (VEGF). These findings indicate that HDT with
      SCT is effective, even on renal lesions in patients with POEMS syndrome, and
      suggest that high serum VEGF concentrations are associated closely with the
      development of renal lesions in patients with this type of plasma cell disorder.

PMID- 16564946
TI  - Acquired hemophilia in association with ANCA-associated vasculitis: response to
      rituximab.
AB  - We describe a patient with end-stage renal disease secondary to antineutrophil
      cytoplasmic antibody-associated vasculitis who subsequently developed acquired
      hemophilia A with autoantibodies to factor VIII. This is a novel association.
      Previous vasculitis therapy with the anti-CD52 monoclonal antibody Campath-1H may
      have contributed to the development of a second autoimmune disease in this
      patient by inadvertent depletion of regulatory T cells. The hemophilia followed a
      relapsing course under oral corticosteroid therapy, but B-cell depletion with
      anti-CD20 monoclonal antibody (rituximab) was effective in inducing a prolonged
      remission.

PMID- 16564947
TI  - EPO adjuvant treatments: a need for more evidence.

PMID- 16564949
TI  - Acute renal failure in a liver transplant patient after treatment with sirolimus.

PMID- 16564950
TI  - Encapsulating peritoneal sclerosis: an unpredictable and devastating complication
      of peritoneal dialysis.

PMID- 16564951
TI  - The role of nephrologists in teaching urinary sediment examination.

PMID- 16564952
TI  - Hematuria in renal transplant patients with BK nephropathy.

PMID- 16564954
TI  - Exiguobacterium mexicanum sp. nov. and Exiguobacterium artemiae sp. nov.,
      isolated from the brine shrimp Artemia franciscana.
AB  - Two Gram-positive strains isolated from cysts of the brine shrimp Artemia
      franciscana were subjected to a polyphasic taxonomic analysis. Based on 16S rRNA
      gene sequence comparison and composition of isoprenoid quinones, peptidoglycan
      and fatty acids, these organisms are members of the genus Exiguobacterium. Both
      strains showed 95.9% 16S rRNA gene sequence similarity to one another. The 16S
      rRNA gene sequences of strain 8N(T) and 9AN(T) were 97.5% and 98.9% similar to
      those of Exiguobacterium aurantiacum DSM 6208(T) and Exiguobacterium undae DSM
      14481(T), respectively. Based on differences in chemotaxonomic and physiological
      characteristics, results of DNA-DNA hybridization and automated riboprinting, two
      novel species of the genus Exiguobacterium are proposed, Exiguobacterium
      mexicanum sp. nov. (type strain 8N(T)=DSM 16483(T)=CIP 108859(T)) and
      Exiguobacterium artemiae sp. nov. (type strain 9AN(T)=DSM 16484(T)=CIP
      108858(T)).

PMID- 16564955
TI  - Dokdonella fugitiva sp. nov., a Gammaproteobacterium isolated from potting soil.
AB  - A Gram-negative bacterium designated A3(T) was isolated from a potting soil
      produced in Portugal. This organism formed rod-shaped cells, was non-motile and
      strictly aerobic. Strain A3(T) was catalase-negative, weakly oxidase positive,
      with an optimum growth temperature of 40 degrees C and an optimum pH value for
      growth of 7.0. The predominant cellular fatty acids detected were iso-17:1
      omega9c, iso-17:0, iso-15:0, iso-16:0 and iso-11:0 3OH and the major respiratory
      quinone was ubiquinone 8. The G+C content of DNA was 68.3%. The phylogenetic
      analyses based on the 16S rRNA sequencing showed that the closest relative of
      strain A3(T) was the type strain of Dokdonella koreensis indicating that the
      organism is a member of the family Xanthomonadaceae, class Gammaproteobacteria.
      Based on the phylogenetic analyses and distinct phenotypic characteristics, we
      are of the opinion that strain A3(T), represents a novel species of the genus
      Dokdonella for which we propose the name Dokdonella fugitiva sp.nov.

PMID- 16564956
TI  - Azorhizobium doebereinerae sp. Nov. Microsymbiont of Sesbania virgata (Caz.)
      Pers.
AB  - Thirty-four rhizobium strains were isolated from root nodules of the fast-growing
      woody native species Sesbania virgata in different regions of southeast Brazil
      (Minas Gerais and Rio de Janeiro States). These isolates had cultural
      characteristics on YMA quite similar to Azorhizobium caulinodans (alkalinization,
      scant extracellular polysaccharide production, fast or intermediate growth rate).
      They exhibited a high similarity of phenotypic and genotypic characteristics
      among themselves and to a lesser extent with A. caulinodans. DNA:DNA
      hybridization and 16SrRNA sequences support their inclusion in the genus
      Azorhizobium, but not in the species A. caulinodans. The name A. doebereinerae is
      proposed, with isolate UFLA1-100 (=BR5401, =LMG9993=SEMIA 6401) as the type
      strain.

PMID- 16564958
TI  - Estimation of ribosomal RNA operon (rrn) copy number in Acinetobacter isolates
      and potential of patterns of rrn operon-containing fragments for typing strains
      of members of this genus.
AB  - The copy number of the rrn operon in 70 strains of Acinetobacter including the
      type strains of almost all the genomic species with validated names was estimated
      after digestion of their genomic DNA by the restriction enzymes BglII and PstI,
      and Southern blotting. Copy number estimates varied between and among species,
      with between 3 and 7 rrn operon copies detected. Copy number estimates obtained
      from the same strain with the two enzymes sometimes varied. BglII generated RFLP
      patterns of the rrn containing fragments obtained from Southern blots after
      agarose gel electrophoresis were examined for their value in identifying
      Acinetobacter isolates. This method was very reproducible with the same fragment
      pattern always generated from the same isolate on repeated analysis. Often
      multiple strains of the same genomic species gave identical or very similar
      patterns (e.g. Acinetobacter baylyi), clustering closest together on the
      dendrogram generated after numerical analysis of these patterns. However, with
      some, like BG5 and BG8, the patterns derived from the different strains, some of
      which had been placed in this genomic species from DNA:DNA hybridization data,
      varied considerably to each other and to the type strain. Little similarity was
      seen when relationships between these strains based on these patterns were
      compared to those using DNA:DNA hybridization data. Often these patterns could be
      used to question earlier identification of strains using phenotypic characters.
      Thus, strain AB82 thought to belong to genomic species 5 gave an identical
      pattern to A. bouvetii(T) (DSM 14964). In some cases this pattern analysis
      suggested that novel species of Acinetobacter might exist among the strains
      examined.

PMID- 16564957
TI  - Proposal for combining Bradyrhizobium spp. (Aeschynomene indica) with
      Blastobacter denitrificans and to transfer Blastobacter denitrificans (Hirsch and
      Muller, 1985) to the genus Bradyrhizobium as Bradyrhizobium denitrificans (comb.
      nov.).
AB  - The symbiotic bradyrhizobia of Aeschynomene indica and the aquatic budding
      bacterium Blastobacter denitrificans have much in common and this study broadens
      the characters that are shared between the two. The 23S rRNA gene sequences of
      the bradyrhizobial isolates were most similar to each other and to the sequence
      of Bl. denitrificans. Evidence for the presence of photosynthetic genes in the
      genome of Bl. denitrificans was obtained by PCR using primers to the conserved M
      subunit (pufM) of the photosynthetic reaction center present in purple sulfur and
      purple nonsulfur bacteria. The deduced amino acid sequences of the partial PufM
      protein of Bl. denitrificans and the corresponding sequences obtained from the
      bradyrhizobial isolates were identical. Both the bradyrhizobial isolates and the
      type strain of Bl. denitrificans shared the ability to propagate by budding,
      demonstrated by electron microscopy. Even though many interspecific characters
      were shared among the bradyrhizobial isolates including Bl. denitrificans, it was
      evident from Amplified Fragment Length Polymorphism (AFLP) analysis that genomic
      variation existed among the collection that was examined. Variation among
      bradyrhizobial isolates and Bl. denitrificans also was established in carbon and
      nitrogen source utilization and the ability to grow at elevated temperature.
      Based on these results and previously reported evidence it is suggested that the
      type strain for Bl. denitrificans and the bradyrhizobial isolates from nodules of
      A. indica belong to a common group of bacteria. Therefore, it is proposed that
      they be combined into the genus Bradyrhizobium and that LMG 8443 be transferred
      to this genus as the type strain for B. denitrificans.

PMID- 16564959
TI  - Characterization of psychrotolerant heterotrophic bacteria from Finnish Lapland.
AB  - A total of 331 aerobic heterotrophic bacterial strains were isolated from various
      ecosystems of Finnish Lapland (68-69 degrees N) including forest soil, arctic
      alpine-tundra soil, stream water, lake and mire sediments, lichen and snow algae.
      Whole cell fatty acid and 16S rRNA gene sequence analysis and microscopy
      indicated that the isolates were dominated by Gram-negative bacteria, while only
      20 Gram-positive strains were isolated. Based on 16S rRNA gene sequences the
      isolates were members of alpha-, beta-, gamma-Proteobacteria, Gram-positives with
      low G+C content, Actinobacteria and the Cytophaga/Flexibacter/Bacteroides group.
      More than one-third of the isolates could be tentatively identified as
      Pseudomonas spp. which were particularly abundant in the alpine-tundra soils
      where they represented 60% of all isolates. Other frequently isolated Gram
      negative taxa were Burkholderia sp., Collimonas sp., Pedobacter sp.,
      Janthinobacter sp., Duganella sp., Dyella sp. and Sphingomonas sp. Growth
      temperature ranges and hydrolytic enzyme activities of selected ca.100 strains
      were screened. The strains were psychrotolerant growing generally at temperatures
      ranging from 0 to 30 degrees C, as 82% of the isolates grew at 0 degrees C while
      only 7% grew at 35 degrees C. Protease and lipase activities at 5 degrees C were
      detected in more than half of the strains while approximately 20% of the strains
      possessed amylase and/or cellulase activities.

PMID- 16564960
TI  - Selection and identification of bacteria isolated from waste crude oil with
      polycyclic aromatic hydrocarbons removal capacities.
AB  - Fifteen bacterial strains isolated from solid waste oil samples were selected due
      to their capacity of growing in the presence of hydrocarbons. The isolates were
      identified by PCR of the 16S rDNA gene using fD1 and rD1 primers. The majority of
      the strains belonged to genera Bacillus, Bacillus pumilus (eight strains) and
      Bacillus subtilis (two strains). Besides, three strains were identified as
      Micrococcus luteus, one as Alcaligenes faecalis and one strain as Enterobacter
      sp. Growth of the above-mentioned strains in mineral liquid media amended with
      naphthalene, phenanthrene, fluoranthene or pyrene as sole carbon source was
      studied and our results showed that these strains can tolerate and remove
      different polycyclic aromatic hydrocarbons that may be toxic in the environment
      polluted with hydrocarbons. Finally, the capacity of certain strains to emulsify
      octane, xilene, toluene, mineral oil and crude oil, and its ability to remove
      hydrocarbons, look promising for its application in bioremediation technologies.

PMID- 16564961
TI  - Molecular diversity of native bradyrhizobia isolated from lima bean (Phaseolus
      lunatus L.) in Peru.
AB  - The diversity of a collection of 21 bradyrhizobial isolates from Lima bean
      (Phaseolus lunatus L.) was assayed by molecular methods. Moderately high to high
      genetic diversity was revealed by multilocus enzyme electrophoresis (MLEE)
      analysis of seven enzyme loci and genomic fingerprints with ERIC and BOX primers.
      Two groups with differences in growth rate were found among the isolates and
      their differentiation as two divergent bradyrhizobial lineages was supported by
      PCR-RFLP of the rpoB gene and sequence analysis of the 16S rDNA and dnaK genes.
      Isolates with slow growth (SG) were identified as Bradyrhizobium yuanmingense,
      while extra-slow growing isolates (ESG) constitute a new lineage different from
      all described Bradyrhizobium species. Three distinct symbiotic genotypes were
      detected among Lima bean bradyrhizobia by PCR-RFLP and sequence analysis of the
      nifH and nodB genes. One genotype was found in the ESG lineage and two in B.
      yuanmingense. Another symbiotic genotype was detected in B. yuamingense isolated
      from Lespedeza plants. The identified bradyrhizobial lineages constitute
      sympatric species effectively nodulating Lima bean on the coast of Peru.

PMID- 16564962
TI  - Toxic anterior segment syndrome.

PMID- 16564963
TI  - Correlation of infrared pupillometers and CCD camera imaging from aberrometry and
      videokeratography for determining scotopic pupil size.

PMID- 16564965
TI  - Long-term intraocular pressure control after clear corneal phacoemulsification in
      glaucoma patients.

PMID- 16564967
TI  - Prognosis of pseudophakic retinal detachment.

PMID- 16564968
TI  - Aberrations after intraocular lens implantation.

PMID- 16564971
TI  - Intraocular lens-capsular bag imaging with ultrahigh-resolution optical coherence
      tomography: pseudophakic human autopsy eyes.

PMID- 16564972
TI  - Unusual cause of visual symptoms after bilateral laser in situ keratomileusis.

PMID- 16564975
TI  - Severe anaphylactic reaction after intracameral antibiotic administration during
      cataract surgery.

PMID- 16564977
TI  - Pupil response to tropicamide following LASIK.

PMID- 16564979
TI  - Measurement of photic phenomena.

PMID- 16564980
TI  - Biometry accuracy.

PMID- 16564981
TI  - Consultation section. Cataract surgical problem.

PMID- 16564993
TI  - Transscleral intraocular lens fixation with a "homemade" needle and hook.
AB  - We describe an ab externo, transscleral, intraocular lens (IOL) fixation
      technique using a surgeon-fashioned 25-gauge hook, a neodymium:yttrium aluminum
      garnet (Nd:YAG)-modified 27-gauge needle, and 9-0 polypropylene suture. This is a
      simple, inexpensive technique for creating small-gauge surgical instruments to
      accurately and atraumatically pass 9-0 and 10-0 polypropylene sutures through
      sclera. Holes, through which sutures can be threaded, are "burned" near the tips
      of 27-gauge or 30-gauge needles with an Nd:YAG laser. Using a fine needle holder,
      a 25-gauge hook is fashioned from a hypodermic needle. A surgical technique
      incorporating 2 ab externo incisions and achieving transscleral posterior chamber
      IOL fixation is discussed.

PMID- 16564995
TI  - Improved contrast sensitivity and visual acuity after wavefront-guided laser in
      situ keratomileusis: in-depth statistical analysis.
AB  - PURPOSE: To evaluate changes in contrast sensitivity and visual acuity following
      wavefront-guided laser in situ keratomileusis (LASIK) procedures with the Visx
      CustomVue system. SETTING: Six clinical sites that participated in an
      Investigational Device Exemption clinical study. METHODS: Two hundred seventy
      four myopic astigmatic eyes (spherical equivalent range -0.63 to -6.00 diopters)
      completed 6 months of follow-up examinations. Wavefront-guided procedures using
      the WaveScan aberrometer and Star S4 excimer laser system with variable spot
      scanning were performed at 6 clinical locations. Visual acuity and contrast
      sensitivity under photopic, mesopic, and mesopic-with-glare lighting conditions
      were tested preoperatively and over a 6-month follow-up period. This study was a
      retrospective analysis of contrast sensitivity data with controls for the effects
      of retinal magnification, mesopic pupil size, and the influence of prior soft
      contact lens wear on visual outcome. RESULTS: Patients experienced statistically
      significant improvements in contrast sensitivity at all spatial frequencies and
      under all lighting conditions (P<.05, Student t test). Contrast sensitivity under
      mesopic conditions with glare improved in 40% of patients. There was more
      improvement at higher (12 cycles per degree [cpd], 18 cpd) than lower (3 cpd)
      spatial frequencies. No correlation was found between mesopic pupil size and
      contrast sensitivity. Results stratified by spectacle or soft contact lens wear
      were similar. Soft contact lens wearers had slightly higher disability glare
      scores than spectacle wearers. CONCLUSIONS: A significant number of patients
      experienced improved corneal optical quality after wavefront-guided LASIK. The
      contrast sensitivity in most patients was unchanged. Contrast sensitivity
      improved in a significant number of patients. There was no correlation between
      mesopic pupil size and mesopic or mesopic-with-glare contrast performance.
      Spectacle wearers improved more than soft contact lens wearers.

PMID- 16564994
TI  - Comparative higher-order aberration measurement of the LADARWave and Visx
      WaveScan aberrometers at varying pupil sizes and after pharmacologic dilation and
      cycloplegia.
AB  - PURPOSE: To compare higher-order aberration (HOA) measurements of LADARWave and
      Visx WaveScan aberrometers, to test the validity of the peripheral wavefront
      data, and to evaluate the effect of pharmacologic dilation and mild cycloplegia.
      METHODS: Thirty-three myopic eyes of 17 volunteers were enrolled and had the
      ocular HOAs measured and analyzed with varying pupil diameters (PD) controlled by
      a tunable light intensity source and after instillation of tropicamide 1% and
      phenylephrine 2.5%. RESULTS: Higher-order aberrations increased with PD and
      optical zone (OZ), especially an OZ between 6.0 mm and 6.5 mm. Spherical
      aberration increased the most, followed by coma, then trefoil and secondary
      astigmatism. Measurement differences were observed between LADARWave and WaveScan
      at an OZ of 6.0 mm, although measurement correlations between the 2 machines were
      high. In the case of the WaveScan, when PD = OZ (6.0 mm), the spherical
      aberration and, to a less extent, the coma data differed from those obtained with
      larger PDs and the same OZ. In the case of the LADARWave, at an OZ of 6.0 mm, the
      HOAs measured in eyes with physiologic pupils were similar to those in
      pharmacologically dilated pupils when the physiologic pupil center was taken as
      the reference. CONCLUSIONS: There were detectable measurement differences between
      LADARWave and Visx WaveScan. Ensuring that the PD is at least 0.5 mm larger than
      the desired OZ is very important. Dilation and mild cycloplegia did not
      clinically affect the wave measurement magnitude or pattern.

PMID- 16564996
TI  - Pseudophakic accommodation with 2 models of foldable intraocular lenses.
AB  - PURPOSE: To evaluate the amplitude of pseudophakic accommodation of 2 foldable
      intraocular lenses (IOLs) by measuring the anterior chamber depth (ACD) shift
      during a 1-year follow-up. SETTING: Department of Ophthalmology, Medical and
      Health Science Center, University of Debrecen, Debrecen, Hungary. METHODS: This
      prospective study comprised 44 eyes of 44 cataract patients operated on with
      phacoemulsification and in-the-bag implantation of Akreos Disc (22 eyes) or
      AcrySof MA60BM (22 eyes) IOLs. The ACD was measured by A-scan during fixation at
      30 cm and again after instillation of cyclopentolate 1%. The ACD shift was
      calculated by subtracting the ACD under cyclopentolate from the ACD during
      fixation at 30 cm. Follow-up measurements were performed 3, 6, and 12 months
      after surgery. Statistical analysis concerning the difference between the 2
      groups was done by the Student unpaired t test. RESULTS: The ACD shift was
      greater in the AcrySof group than in the Akreos Disc group at all 3 follow-up
      examinations. The difference was highly significant between the 2 groups at 6 and
      12 months (both P = .004). After the operation, the ACD shift increased
      continuously with time in both groups. The mean ACD shift reached 0.57 mm +/-
      0.25 (SD) in the AcrySof group and 0.42 +/- 0.24 mm in the Akreos group at 12
      months. CONCLUSIONS: The 3-piece AcrySof MA60BM IOL with 10-degree posterior
      angulation had a significantly higher capacity for pseudophakic accommodation
      than the 1-piece plate-haptic Akreos Disc IOL. The continuous increase in the ACD
      shift in the postoperative period may mean that patients learn to achieve better
      accommodation with an IOL as time goes on.

PMID- 16564997
TI  - Toxic anterior segment syndrome and possible association with ointment in the
      anterior chamber following cataract surgery.
AB  - PURPOSE: To report clinical and laboratory findings of 8 cases of toxic anterior
      segment syndrome (TASS) related to an oily substance in the anterior chamber of
      patients following cataract surgery with intraocular lens (IOL) implantation.
      SETTING: John Moran Eye Center, University of Utah, Salt Lake City, Utah, USA.
      METHODS: Eight patients had uneventful phacoemulsification by the same surgeon
      via clear corneal incisions with implantation of the same 3-piece silicone IOL
      design. Postoperative medications included antibiotic/steroid ointment and
      pilocarpine gel; each eye was firmly patched at the end of the procedure. On the
      first postoperative day, some patients presented with diffuse corneal edema,
      increased intraocular pressure, and an oily film-like material within the
      anterior chamber coating the corneal endothelium. The others presented with an
      oily bubble floating inside the anterior chamber, which was later seen coating
      the IOL. Additional surgical procedures required included penetrating
      keratoplasty, IOL explantation, and trabeculectomy. Two corneal buttons were
      analyzed histopathologically. Two explanted IOLs had gross and light microscopic
      analyses (as well as surface analyses of 1 of them), and 4 other explanted IOLs
      had gas chromatography-mass spectrometry. RESULTS: Pathological examination of
      the corneas showed variable thinning of the epithelium with edema. The stroma was
      diffusely thickened and the endothelial cell layer was absent. Evaluation of the
      explanted IOLs confirmed the presence of an oily substance coating large areas of
      their anterior and posterior optic surfaces. Gas chromatography-mass spectrometry
      of the lens extracts identified a mixed chain hydrocarbon compound that was also
      found in the gas chromatography-mass spectrometry analyses of the ointment used
      postoperatively. CONCLUSIONS: The results indicate that the ointment gained
      access to the eye, causing the postoperative complications described. These cases
      highlight the importance of appropriate wound construction and integrity, as well
      as the risks of tight eye patching following placement of ointment.

PMID- 16564998
TI  - Color perception with AcrySof natural and AcrySof single-piece intraocular lenses
      under photopic and mesopic conditions.
AB  - PURPOSE: To examine color perception in patients receiving bilateral implantation
      of an ultraviolet (UV) and blue-light filtering intraocular lens (IOL) (AcrySof
      Natural SN60AT, Alcon Laboratories Inc.) or a UV-only filtering IOL (AcrySof
      SA60AT) and to compare the results with those in a phakic group. SETTING:
      Cincinnati, Ohio, USA. METHODS: In this prospective study, age-matched subjects
      who passed the Ishihara test and had visual acuities of 20/25 or better were
      recruited. There were 2 pseudophakic groups (bilateral SN60AT or SA60AT IOLs) and
      1 phakic group. The Farnsworth-Munsell (FM) 100-hue test was administered to each
      subject twice under different conditions. The phakic and AcrySof Natural SN60AT
      groups were tested under photopic and mesopic conditions. The SA60AT subjects
      were further divided into subgroups (with and without yellow clip-on lenses) and
      tested under photopic and mesopic conditions. RESULTS: A 1-way analysis of
      variance (ANOVA) of the square-root-transformed total error score showed no
      statistical differences (P = .637) between the treatment groups. Similarly, a 1
      way ANOVA of the red-green error score (P = .729) and blue-yellow error score (P
      = .484) indicated no statistically significant differences between the treatment
      groups. The ANOVA results of the FM 100-hue test under mesopic conditions showed
      that the total error score in the AcrySof Natural IOL group was significantly
      lower (P = .046) than in the phakic group. There were no between-group
      differences in error scores under mesopic conditions. CONCLUSION: The FM 100-hue
      testing showed no difference in color perception between subjects with AcrySof
      Natural IOLs and those in an age-matched phakic control group or in those with a
      UV-only filtering AcrySof IOL with or without yellow clip-on lenses.

PMID- 16564999
TI  - Toric phakic intraocular lens for the correction of hyperopia and astigmatism.
AB  - PURPOSE: To evaluate the Artisan toric phakic intraocular lens (pIOL) for the
      correction of hyperopia and astigmatism. SETTING: Department of Ophthalmology,
      Erasmus MC, Rotterdam, The Netherlands, and Department of Ophthalmology, Sint
      Truiden, Belgium. METHODS: In this prospective study of 47 eyes of 28 patients
      with hyperopia and astigmatism, Artisan toric pIOLs were implanted between April
      1999 and June 2004. Uncorrected visual acuity (UCVA), best corrected visual
      acuity, refraction, astigmatism, safety, and predictability were analyzed. Change
      in astigmatism was analyzed with vector analysis. Refractive cylinders are
      expressed in minus form. RESULTS: Mean preoperative spherical equivalent was
      +4.33 diopters (D) +/- 2.26 (SD). Mean follow-up was 11.1 months (range 6 to 36
      months). A gain of 1 or more lines in best spectacle-corrected visual acuity
      (BSCVA) was seen in 36.2%. Safety index and efficacy index after 6 months were
      1.06 and 0.87, respectively. The mean postoperative astigmatism at 6 months was
      0.19 D at an axis of 144 degrees. At 6 months, about three quarters (76.6%) of
      the eyes had a UCVA of 20/40 or better. One eye lost 2 lines of BSCVA. In 1 eye,
      the lens position had to be changed because of a large axis misalignment. No
      serious complications developed in any of the treated eyes during follow-up.
      CONCLUSIONS: Artisan toric pIOLs can correct moderate to high hyperopia combined
      with astigmatism with good refractive results. In this study, there were no
      serious complications. However, the predictability of the refractive results
      appeared to be lower than those in the correction of myopia and astigmatism with
      toric Artisan lenses.

PMID- 16565000
TI  - Changes in higher-order aberrations after implantation of a foldable iris-claw
      lens in myopic phakic eyes.
AB  - PURPOSE: To evaluate the change in higher-order aberrations (HOAs) after
      implantation of a foldable iris-claw phakic intraocular lens (pIOL) in myopic
      eyes. SETTING: Department of Ophthalmology, Johannes Gutenberg-University, Mainz,
      Germany. METHODS: This prospective nonrandomized comparative self-controlled
      trial included 41 eyes that had implantation of a foldable iris-claw pIOL between
      July 2003 and November 2004. All patient data for HOAs (Zernike coefficient) were
      measured and calculated using the same pupil size preoperatively and
      postoperatively, and the root-mean-square (RMS) wavefront error was calculated.
      Examinations were performed preoperatively as well as 1 week and 3, 6, and 12
      months after pIOL implantation. RESULTS: The mean preoperative sphere was -8.12
      diopters (D) +/- 2.01 (SD) (range -12.25 to -3.75 D) and the mean preoperative
      cylinder, -0.90 +/- 0.62 D (range -2.50 to 0.00 D). The Z3(1) and Z(3)(-1)
      coefficients decreased after implantation of the foldable iris-claw pIOL, but the
      decrease was not statistically significant (P = .078 and P = .45, respectively).
      There was a statistically significant reduction in Z4(0) in the first
      postoperative week (P = .038), but the decrease was not significant thereafter.
      There was a statistically significant reduction in total RMS wavefront error from
      preoperatively to all values postoperatively (P = .008). CONCLUSION: Over a 12
      month follow-up, 3rd-order and 4th-order HOAs did not increase after foldable
      iris-claw pIOL implantation in myopic eyes.

PMID- 16565001
TI  - Pupil measurement using the Colvard pupillometer and a standard pupil card with a
      cobalt blue filter penlight.
AB  - PURPOSE: To compare scotopic pupil measurements obtained with a Colvard
      pupillometer with measurements taken with a printed pupil gauge and penlight with
      a cobalt blue filter attachment in mesopic and scotopic luminance. SETTING: The
      Illinois Eye Institute, Chicago, Illinois, USA. METHODS: Pupil measurements were
      taken of both eyes of 38 patients (76 eyes). Any subject presenting with anterior
      segment disease, fixed or dilated pupils, iris abnormalities, or a history of eye
      disease or eye trauma was excluded. At a mesopic luminance of 2.11 foot-candles,
      pupil measurements were taken with a Bernell pupil card and penlight with a
      cobalt blue filter attachment. At a scotopic luminance of less than 2.00 foot
      candles, pupil measurements were taken with the Bernell card system and the
      Colvard pupillometer. RESULTS: In mesopic luminance, the mean pupil diameter was
      5.17 mm (range 3.0 to 7.5 mm) with the Bernell card method. The mean difference
      between the Colvard in scotopic luminance and the Bernell card system in mesopic
      luminance was -0.04 mm (P = .0831). In scotopic luminance, the mean pupil
      diameter was 6.32 mm (range 4.0 to 8.0 mm) with the Bernell card method and 5.13
      mm (range 3.0 to 7.5 mm) with the Colvard pupillometer, with a mean difference of
      -1.18 mm (P<.0001). The limits of agreement between the mesopic Bernell card
      system and the Colvard pupillometer were small (-0.32 to 0.24), whereas the
      limits of agreement between the scotopic measurements of both techniques were
      large (-2.18 to -0.18). CONCLUSIONS: Under both illuminance conditions, the
      Bernell card system with the cobalt filter measured a larger pupil size than the
      Colvard pupillometer. The measurement differences between the techniques were
      most pronounced at the lower illumination. The limits of agreement were larger
      under the lower illumination, indicating more variation between techniques. This
      study suggests that the Bernell card system with cobalt illumination provides a
      generous measurement of the pupil size compared with the Colvard pupillometer,
      which makes it an appropriate and cost-effective screening tool for refractive
      surgery evaluation.

PMID- 16565002
TI  - Diagnosis and management of bilateral posterior lenticonus in 7 members of the
      same family.
AB  - PURPOSE: To report on the occurrence of monosymptomatic bilateral posterior
      lenticonus in 7 members of the same family and discuss the diagnoses and methods
      of management. SETTING: Eye Clinic, Cantonal Hospital, Lucerne, Switzerland.
      METHODS: Two sisters were found to suffer from bilateral posterior lenticonus.
      The 3 sons of the elder sister and the 2 daughters of the younger sister all
      presented with bilateral posterior lenticonus. A cataract operation or a clear
      lens extraction with intraocular lens implantation was performed in 4 of the 7
      patients. RESULTS: The disorder was found to be inherited and to follow a pattern
      of autosomal dominance. Visual acuity improved to 20/20 in all operated eyes.
      CONCLUSION: This may be the largest group in 1 family presenting with bilateral
      posterior lenticonus described to date. Treatment of posterior lenticonus, if
      necessary, can be successfully managed as an ordinary cataract.

PMID- 16565003
TI  - Role of topical fluoroquinolones on the pathogenesis of diffuse lamellar
      keratitis in experimental in vivo studies.
AB  - PURPOSE: To investigate the potential role of commercially available topical
      fluoroquinolones in diffuse lamellar keratitis (DLK) using New Zealand White
      rabbit models. SETTING: Campbell Ophthalmic Microbiology Laboratory at the
      University of Pittsburgh, Pittsburgh, Pennsylvania, USA. METHODS: In a DLK
      challenge model, laser in situ keratomileusis flaps were created by a
      microkeratome in rabbit eyes (n = 10 per group) and the stromal beds were treated
      with 1 drop of Ciloxan (ciprofloxacin 0.3%), Ocuflox (ofloxacin 0.3%), balanced
      salt solution (BSS), or Pseudomonas aeruginosa endotoxin before flap closure.
      After the procedure, eyes were treated with the same drugs 4 times daily. On
      postoperative day 1, the eyes were examined by slitlamp and graded (modified
      Linebarger DLK grading scale) in a masked fashion. In a DLK exacerbation model,
      all eyes received 1 drop of endotoxin on the stromal interface followed by flap
      closure. After the procedure, the rabbit eyes (10 per group) were treated 4 times
      daily with Ciloxan, Ocuflox, or BSS and graded for DLK on postoperative day 1 as
      before. RESULTS: In the challenge model, Ciloxan, Ocuflox, and endotoxin all
      produced higher median DLK scores than the BSS control (P = .02). Ciloxan
      produced significant DLK in more eyes and had higher median scores (70%, 1.0)
      than Ocuflox (40%, 0.5) or endotoxin (45%, 0.5) (P = .05). In the endotoxin
      induced model, Ciloxan produced significantly higher DLK scores than Ocuflox or
      BSS (P = .05). CONCLUSIONS: Topical fluoroquinolones caused and exacerbated DLK
      in rabbit models. Ocuflox was associated with less DLK than Ciloxan. The clinical
      significance of these findings can only be assessed in clinical trials.

PMID- 16565004
TI  - Optical analysis of an accommodating intraocular lens.
AB  - PURPOSE: To model the feasibility of an accommodating intraocular lens (IOL) that
      allows near vision by means of an anterior translation within the capsular bag.
      SETTING: University of Waterloo, Waterloo, Ontario, Canada. METHODS: Model eyes
      were constructed and analyzed based on experimental data using Code V, a
      computerized optical design tool. The potential near vision of IOLs of different
      powers was calculated as they were moved anteriorly within the capsular bag. The
      conditions under which a spherical lens performs well and when an aspheric design
      should be considered were determined. RESULTS: Accommodation (the dioptric change
      from the far to the near point) varies linearly with lens movement and is
      sensitive to corneal and IOL powers. Simple equations were derived and accurately
      predicted induced accommodation. Retinal image quality varies significantly with
      pupil size and IOL power. However, image quality is minimally affected by the
      amount of induced accommodation. CONCLUSIONS: From an optical standpoint
      accommodation with adequate image quality can be achieved by anterior movement of
      a spherical IOL within the capsular bag.

PMID- 16565005
TI  - Biomechanical evidence of the distribution of cross-links in corneas treated with
      riboflavin and ultraviolet A light.
AB  - PURPOSE: To examine to which depth of the cornea the stiffening effect is
      biomechanically detectable. SETTING: Department of Ophthalmology, University of
      Dresden, Dresden, Germany. METHODS: Of 40 enucleated porcine eyes, 20 eyes were
      treated with the photosensitizer riboflavin (0.1%) and ultraviolet A (UVA) light
      (370 nm, 3 mW/cm2, 30 minutes); the other 20 eyes served as control. From each
      eye, 2 flaps of 200 microm thickness were cut with a microkeratome, and strips of
      5 mm width and 7 mm length were prepared. Stress-strain behavior was measured
      with a material tester to characterize the stiffening effect. Five pairs of human
      donor eyes were tested in the same way. RESULTS: In porcine corneas, the
      stiffening effect was stronger in the anterior-treated flaps than in the
      posterior-treated flaps and the control flaps (P = .001). A 5% strain was
      achieved at a stress of 261.7 +/- 133.2 x 10(3) N/m2 in the anterior-treated
      flaps and 104.1 +/- 52.7 x 10(3) N/m2 in the anterior control flaps. The
      posterior-treated flaps (105.0 +/- 55.8 x 10(3) N/m2) and the posterior control
      flaps (103.7 +/- 61.8 x 10(3) N/m2) showed no difference (P = .95). A similar
      stiffening effect was observed in human eyes, but contrary to findings in porcine
      corneas, in human corneas the anterior control flaps were stiffer than the
      posterior control flaps (P = .027). CONCLUSIONS: Treatment of the cornea with
      riboflavin and UVA significantly stiffened the cornea only in the anterior 200
      microm. This depth-dependent stiffening effect may be explained by the absorption
      behavior for UVA in the riboflavin-treated cornea. Sixty-five percent to 70% of
      UVA irradiation was absorbed within the anterior 200 microm and only 20% in the
      next 200 microm. Therefore, deeper structures and even the endothelium are not
      affected.

PMID- 16565006
TI  - Ultrasonic-generated fluid velocity with Sovereign WhiteStar micropulse and
      continuous phacoemulsification.
AB  - PURPOSE: To evaluate and compare ultrasonic turbulence created by conventional
      and micropulse ultrasound technology. SETTING: Sonora Medical Systems, Longmont,
      Colorado, USA. METHODS: A high-resolution digital ultrasound probe imaged the
      zone around a phacoemulsification tip. Doppler analysis allowed determination of
      flow. The fluid velocity was measured at 4 levels of ultrasound power at a
      constant flow, comparing the ultrasonic conditions of continuous energy to
      WhiteStar micropulses. RESULTS: In addition to the normal baseline irrigation and
      aspiration, fluid movement was detected directly below the phaco tip, produced by
      a nonlinear effect known as acoustic streaming. Acoustic streaming increased with
      increased phacoemulsification power for both conditions. At each of the 4 levels
      of power, fluid velocity away from the tip was less with micropulse technology
      than with continuous phacoemulsification. CONCLUSIONS: The demonstrated decrease
      in acoustic streaming flow away from the phaco tip with Sovereign WhiteStar
      micropulse technology compared to conventional ultrasound provides an objective
      explanation for clinical observations of increased stability of nuclear fragments
      at the tip and less turbulence in the anterior chamber during
      phacoemulsification. This methodology can be used to examine and compare fluid
      flow and turbulence under a variety of clinically relevant conditions.

PMID- 16565007
TI  - Comparison of thermal features associated with 2 phacoemulsification machines.
AB  - PURPOSE: To determine the thermal characteristics of the Legacy Advantec and
      Sovereign WhiteStar phacoemulsification machines during different clinically
      relevant scenarios. SETTING: In vitro study. METHODS: In water, temperature was
      recorded continuously on the sleeve in an artificial chamber, and the increase in
      temperature over baseline after 60 seconds of ultrasound was determined. This was
      done for continuous ultrasound, 50 ms on and 50 ms off (pulse), 6 ms on and 12 ms
      off (WhiteStar; Sovereign only) with aspiration blocked and not blocked, and with
      100 g and 200 g weights suspended from the sleeve. RESULTS: Comparing temperature
      increase per 20% machine power increments, Sovereign ran hotter than Legacy
      Advantec for continuous ultrasound (2.31x) and pulse (2.23x). Blocking aspiration
      increased temperature over the unblocked state. Pulsing decreased temperature by
      51% (Legacy Advantec, pulse), 52% (Sovereign, pulse), and 64% (WhiteStar).
      Weights had much more effect on the Legacy Advantec: 3.5 times more going from
      baseline to 100 g weights and 3.2 times more going from 100 to 200 g weights. For
      all these comparisons, the P value was less than 0.0001. CONCLUSIONS: The
      machines behaved fundamentally differently, with the Legacy Advantec controlling
      stroke length and Sovereign controlling a fixed power at any setting. Therefore,
      workload had a much bigger impact on Legacy Advantec thermal characteristics.
      Pulsing decreased heat produced directly related to the duty cycle. The most
      dangerous incision burn scenario is with continuous ultrasound, aspiration
      blocked, and a heavy workload.

PMID- 16565008
TI  - Simulating the straylight effects of cataracts.
AB  - PURPOSE: To study the additional straylight falling on the retina (retinal
      straylight) caused by cataract and find commercially available filters to
      simulate the cataract straylight effects. SETTING: Research laboratory. METHODS:
      The retinal straylight addition of cataract was derived from straylight parameter
      data in the literature. The scattering characteristics of cataract-simulating
      filters were measured using a scatterometer. RESULTS: The straylight addition due
      to cataract follows a power law as a function of angle with power of -2.12 and
      straylight parameter log values of up to 1.6 for relatively mild cataract cases.
      Of the commercial filters that were tested, the Tiffen Black Pro Mist (BPM)
      filters resembled the straylight characteristics of cataracts fairly well. The
      filters had a limited effect on visual acuity and contrast sensitivity, which was
      also found for early cataracts. The BPM 2 followed a power law as a function of
      angle with power of approximately -2.21 and straylight log values of 1.12.
      CONCLUSIONS: The BPM 2 filter is a good early-cataract-simulating filter.
      Stacking such filters is a good way to increase the cataract density. A drawback
      is that the BPM 2 filter has a transmission of 66% so stacking filters reduces
      the overall transmission significantly.

PMID- 16565009
TI  - Intraocular pressure during phacoemulsification.
AB  - PURPOSE: To assess changes in intraocular pressure (IOP) during standard coaxial
      or bimanual microincision phacoemulsification. SETTING: Oregon Eye Center,
      Eugene, Oregon, USA. METHODS: Bimanual microincision phacoemulsification
      (microphaco) was performed in 3 cadaver eyes, and standard coaxial
      phacoemulsification was performed in 1 cadaver eye. A pressure transducer placed
      in the vitreous cavity recorded IOP at 100 readings per second. The
      phacoemulsification procedure was broken down into 8 stages, and mean IOP was
      calculated across each stage. Intraocular pressure was measured during bimanual
      microphaco through 2 different incision sizes and with and without the Cruise
      Control (Staar Surgical) connected to the aspiration line. RESULTS: Intraocular
      pressure exceeded 60 mm Hg (retinal perfusion pressure) during both standard
      coaxial and bimanual microphaco procedures. The highest IOP occurred during
      hydrodissection, ophthalmic viscosurgical device injection, and intraocular lens
      insertion. For the 8 stages of the phacoemulsification procedure delineated in
      this study, IOP was lower for at least 1 of the bimanual microphaco eyes compared
      with the standard coaxial phaco eye in 4 of the stages (hydro steps, nuclear
      disassembly, irritation/aspiration, anterior chamber reformation). CONCLUSION:
      There was no consistent difference in IOP between the bimanual microphaco eyes
      and the eye that had standard coaxial phacoemulsification. Bimanual microincision
      phacoemulsification appears to be as safe as standard small incision
      phacoemulsification with regard to IOP.

PMID- 16565010
TI  - Topographic screening of donor eyes for previous refractive surgery.
AB  - PURPOSE: To determine whether donor eyes had previous refractive surgery using
      Orbscan (Bausch & Lomb Surgical) corneal topography. SETTING: Lions Eye Bank of
      Oregon, Portland, Oregon, USA, and Maisonneuve-Rosemont, Hospital, Montreal,
      Quebec, Canada. METHODS: Orbscan corneal topographies of 50 donor eyes from the
      Lions Eye Bank of Oregon were obtained; 10 eyes had previous refractive surgery
      (6 laser in situ keratomileusis, 2 photorefractive keratectomy, 2 radial
      keratotomy) to correct myopia, and 40 had not had surgery. Algorithms based on
      corneal anterior and posterior elevations and anterior tangential curvature were
      developed: The difference in curvature (DC) was based on the difference in the
      mean anterior tangential curvature between central and midperipheral areas;
      difference in elevation (DE) represented the difference between the anterior and
      posterior central elevations. Receiver-operating characteristic (ROC) curves for
      each algorithm were obtained, and sensitivity values at fixed specificities were
      calculated. RESULTS: The mean area under the ROC curve, which corresponds to the
      probability of correctly identifying the presence of a previous refractive
      surgery, was 0.853 +/- 0.079 (SE) for DC and 0.933 +/- 0.057 for DE. The DC
      algorithm resulted in a sensitivity of 80% for a specificity of 87.5%, and DE
      yielded a sensitivity of 90% for a specificity of 92.5%. There was a strong
      correlation between the value of the DE and DC algorithms and the amount of
      previous refractive surgery (DC: r = 0.84, P = .008; DE: r = 0.76, P = .028).
      CONCLUSION: The results led to a proposed criteria-based system using Orbscan
      corneal topography to screen eye-bank eyes for previous refractive surgery.

PMID- 16565011
TI  - Scanning electron microscopic analysis of acrylic intraocular lenses for
      microincision cataract surgery.
AB  - PURPOSE: To analyze the surface quality before and after folding of 2 intraocular
      lens (IOL) models designed for microincision cataract surgery. SETTING: Eye
      Clinic and Department of Human Pathology and Oncology, University of Florence,
      Florence, Italy. METHODS: Two IOL models now available for sub-2.0 mm
      microincision were studied: UltraChoice 1.0 Rollable ThinLens (ultrathin lens by
      ThinOptX) and AcriSmart (foldable lens by AcriTec). Eight IOLs of each model were
      examined. Scanning electron microscopy (SEM) was performed before and after IOL
      folding with a dedicated injector. Special attention was given to the optic
      surface and edges, the optic-haptic junction, and the haptic itself. RESULTS:
      Initially, the surface quality of IOLs was evaluated before folding. On SEM,
      smooth and homogeneous optic and haptic surfaces were revealed in both IOL models
      with no surplus material or molding flashes; edge finish of all optics showed no
      evidence of ridges. The IOL surfaces were evaluated after insertion into their
      injectors and after ejection at room temperature. After folding, the
      microincision IOLs showed no sign of surface alteration, probably because of
      their high water content, which makes these IOLs soft and flexible. CONCLUSIONS:
      Visual results and long-term biocompatibility of the IOLs are influenced by
      surface properties. In recent years, there has been a trend toward microincision
      cataract surgery. Our study shows that the 2 IOL models now available for sub-2.0
      mm microincision have acceptable surface properties.

PMID- 16565012
TI  - Toxic anterior segment syndrome.
AB  - Toxic anterior segment syndrome (TASS) is a sterile postoperative inflammatory
      reaction caused by a noninfectious substance that enters the anterior segment,
      resulting in toxic damage to intraocular tissues. The process typically starts 12
      to 48 hours after cataract/anterior segment surgery, is limited to the anterior
      segment of the eye, is always Gram stain and culture negative, and usually
      improves with steroid treatment. The primary differential diagnosis is infectious
      endophthalmitis. Review of the literature indicates that possible causes of TASS
      include intraocular solutions with inappropriate chemical composition,
      concentration, pH, or osmolality; preservatives; denatured ophthalmic
      viscosurgical devices; enzymatic detergents; bacterial endotoxin; oxidized metal
      deposits and residues; and factors related to intraocular lenses such as residues
      from polishing or sterilizing compounds. An outbreak of TASS is an environmental
      and toxic control issue that requires complete analysis of all medications and
      fluids used during surgery, as well as complete review of operating room and
      sterilization protocols.

PMID- 16565013
TI  - Ophthalmology and vision science research: part 5: surfing or sieving--using
      literature databases wisely.
AB  - Literature databases are an ever-expanding resource available to the field of
      medical sciences. Understanding how to use such databases efficiently is critical
      for those involved in research. However, for the uninitiated, getting started is
      a major hurdle to overcome and for the occasional user, the finer points of
      database searching remain an unacquired skill. In the fifth and final article in
      this series aimed at those embarking on ophthalmology and vision science
      research, we look at how the beginning researcher can start to use literature
      databases and, by using a stepwise approach, how they can optimize their use.
      This instructional paper gives a hypothetical example of a researcher writing a
      review article and how he or she acquires the necessary scientific literature for
      the article. A prototype search of the Medline database is used to illustrate how
      even a novice might swiftly acquire the skills required for a medium-level
      search. It provides examples and key tips that can increase the proficiency of
      the occasional user. Pitfalls of database searching are discussed, as are the
      limitations of which the user should be aware.

PMID- 16565014
TI  - Late opacification of a silicone intraocular lens caused by ophthalmic ointment.
AB  - A 55-year-old man had uneventful phacoemulsification with implantation of a 3
      piece silicone intraocular lens (IOL). Postoperative medications included
      antibiotic-steroid drops and ointments. Eight months postoperatively, the patient
      started having recurrent episodes of anterior chamber inflammatory reaction.
      Suspicion that lens instability was causing the reactions led to a lens
      repositioning procedure 11 months after the initial surgical implantation and
      again at 13 months. Eighteen months postoperatively, the IOL had a "greasy" film.
      Despite antiinflammatory and antibiotic treatment, the clinical outcome did not
      improve. Twenty-seven months after implantation, the lens was exchanged with a
      hydrophilic acrylic IOL. The course after the exchange was uneventful. The
      explanted lens was examined by gross and microscopic evaluations, scanning
      electron microscopy, energy-dispersive X-ray spectroscopy, and gas chromatography
      mass spectrometry (GC-MS) using electronic ionization. Gross and microscopic
      evaluations confirmed the presence of a thin, oily film covering the IOL optic
      surface. Surface analyses at the level of the oily substance showed unspecific
      peaks of sodium, chloride, and potassium. The GC-MS analysis showed the presence
      of compounds characteristic of hydrocarbons, including docosane, tricosane, and
      tetracosane, which are commonly found in the vehicle of ophthalmic ointments. The
      GC-MS analysis of 1 ointment used postoperatively found matching peaks,
      suggesting deposition of those compounds on the IOL.

PMID- 16565015
TI  - Asymmetric vault of an accommodating intraocular lens.
AB  - We report a case of a new syndrome, late asymmetric vault of the AT45 Crystalens
      intraocular lens (IOL) (Eyeonics Inc.). The late vault, which occurred in 6 month
      after implantation of the IOL, caused a decrease in uncorrected distance and near
      acuities and minus-cylinder axis perpendicular to the haptics. Treatment with
      neodymium:YAG laser capsulotomy and fibrotic band release was successful.

PMID- 16565016
TI  - Incomplete capsular bag distension syndrome after neodymium:YAG capsulotomy.
AB  - We report a 60-year-old man with incomplete capsular bag distension syndrome 2
      years after neodymium:YAG (Nd:YAG) laser capsulotomy for capsule opacification,
      which developed from extracapsular cataract extraction with intraocular lens
      (IOL) implantation performed 4 years before presentation to our clinic. The
      patient reported floaters of 15 days duration. Slitlamp examination showed
      shallowing of the inferior and medial anterior chamber. Dilated pupil examination
      showed a peripheral capsular bag inferiorly and medially behind the IOL. The bag
      was distended and filled with turbid fluid. The central and superior capsule was
      absent as a result of the previous Nd:YAG treatment. The IOL lie over the
      anterior capsule, and peripheral capsule leaves' edges were adhered. An Nd:YAG
      laser puncture of the incomplete capsular bag resolved the condition.

PMID- 16565017
TI  - Stage 4 diffuse lamellar keratitis after laser in situ keratomileusis Clinical,
      topographical, and pachymetry resolution 5 years later.
AB  - In March 1999, a 35-year-old woman had uneventful laser in situ keratomileusis in
      both eyes on the same day. Five days postoperatively, slitlamp biomicroscopy of
      the left eye showed an appearance similar to haze after photorefractive
      keratectomy, with greater density at the center and striae convergent toward the
      infiltrate (stage 4 diffuse lamellar keratitis [DLK]). The patient received
      treatment with dexamethasone 0.2% eyedrops every 2 hours. After 2 weeks, visual
      acuity was better and improvement was evident on topography, pachymetry, and
      slitlamp photography. The improvements were more marked at 6 months and 1 year.
      There was a progressive increment in corneal thickness and consequent improvement
      in corneal transparency, curvature, and regularity. This case, in which
      continuous morphologic adaptation of the cornea occurred, indicates that
      observation, rather than intervention, is a valid therapeutic option for stage 4
      DLK.

PMID- 16565018
TI  - Retained posterior segment indocyanine green dye after phacoemulsification.
AB  - We describe a patient who had indocyanine green (ICG) staining of the anterior
      capsule for phacoemulsification of a traumatic cataract. Intraoperatively, the
      ICG extended into the posterior segment. Postoperatively, the patient developed
      ICG toxicity to the retina and had a vitrectomy to remove the ICG. We believe ICG
      extended into the vitreous through an area of zonular dehiscence.

PMID- 16565019
TI  - Traumatic aniridia in a pseudophakic eye.
AB  - A case is presented that illustrates selective disinsertion and extrusion of iris
      tissue after blunt trauma without damage to the intraocular lens (IOL). This was
      an observational case report of a single patient treated as an inpatient using
      topical steroids and antiglaucoma drugs. Progress was monitored by tonometry and
      slitlamp examination. Total absence of iris tissue was discovered after
      resolution of hyphema with restoration of vision. Absence of iris tissue was
      confirmed on gonioscopy and fundoscopy. The IOL was found undisplaced and intact
      in the capsular bag, and visual function was restored. The insertion of foldable
      IOLs through self-sealing small-incision cataract sections confers protection to
      the globe in the face of blunt trauma in 2 ways. The self-sealing cataract
      section acts as a release valve during the compressive phase and allows extrusion
      of the disinserted iris tissue, whereas the flexible IOL absorbs the impact and
      prevents disruption of surrounding tissues.

PMID- 16565020
TI  - Reopening of 2 macular holes after neodymium:YAG capsulotomy.
AB  - We report 2 cases of reopening of macular holes after successful neodymium:YAG
      (Nd:YAG) posterior capsulotomy. Both patients had surgery for closure of macular
      holes with recovery of visual acuity. To our knowledge, this is the first report
      of recurrent macular holes after Nd:YAG laser posterior capsulotomy treated
      successfully with surgery.

PMID- 16565021
TI  - Opacification of the Acryl C160 hydrophilic acrylic intraocular lens.

PMID- 16565022
TI  - Endophthalmitis prophylaxis for cataract surgery: the first Pakistan survey.

PMID- 16565023
TI  - Cardiac arrest during phacoemulsification using topical anesthesia in an
      unsedated patient.

PMID- 16565024
TI  - The development of West Nile virus safety policies by Canadian blood services:
      guiding principles and a comparison between Canada and the United States.
AB  - To address the emerging threat of West Nile virus (WNV) to the blood supply,
      Canadian Blood Services (CBS) made a series of policy decisions that were either
      similar to those adopted in the United States or more stringent than policies
      formulated in the United States at the same time. More stringent Canadian
      policies included the development of an in-house WNV RNA assay, the stockpiling
      of frozen plasma components in the winter for transfusion in WNV-affected areas
      in the summer, a special recruitment campaign for red blood cell collections
      before the start of the 2003 WNV season, and an inventory exchange (ie, WNV
      tested for untested red blood cells) initiated 2 weeks after the onset of WNV
      screening, as well as the implementation of targeted individual-donation WNV
      testing on August 2, 2004, in the absence of any positive donors or clinical
      cases of WNV infection in Canada. The general principles that guided CBS decision
      making with regard to WNV safety included application of the precautionary
      principle, harmonization with policies in the United States, a consideration of
      logistic issues, compliance with Health Canada requests, responsiveness to public
      expectations about transfusion safety, and transparency in decision making with
      timely communication to stakeholders. Before implementing WNV blood safety
      policies, CBS assessed their impact on blood availability. When policies were
      implemented, data were obtained quickly to ensure that the prior impact
      assessments were accurate. This review discusses the guiding principles affecting
      CBS policy development and compares CBS WNV safety policies to policies adopted
      in the United States.

PMID- 16565025
TI  - Bystander immune cytolysis.
AB  - In addition to alloimmune and autoimmune cell lysis, a third category of immune
      destruction of blood cells should be recognized. This additional immunologic
      response occurs when cells or tissues are injured by immunologic reactions in
      which the cells act as "innocent bystanders." One mechanism by which an immune
      response to an exogenous antigen leads to the destruction of autologous blood
      cells is the temporary development of autoantibodies. This is actually an
      alloimmune reaction which results in a temporary state of "pseudo"-autoimmunity.
      Although originally described as a type of hemolysis of autologous cells, the
      concept of bystander immune cytolysis has been extended to include other
      instances in which immune destruction of cells is caused by antibody that is not
      developed in response to intrinsic antigens on the cell being lysed. In recent
      years, compelling data have been presented documenting bystander immune cytolysis
      in a number of different clinical settings, and efforts have been made to define
      the mechanisms by which this occurs. Physicians must be aware that some examples
      of immune lysis of autologous cells are, in reality, examples of temporary
      bystander immune cytolysis rather than true autoimmune disease. Furthermore, some
      alloimmune hemolytic reactions can result in lysis of bystander cells.

PMID- 16565026
TI  - Perception of blood transfusion risk.
AB  - Perceptions of risk ultimately drive the responses of individuals and society to
      risk issues, and transfusion risk is no exception. Surveys of lay people over the
      past decade indicate that public concern about transfusion safety has remained
      prevalent, dominated by the ongoing fear of contracting HIV infection. Such
      perceptions persist despite the acknowledgment that blood transfusion is safer
      now than in years past. Judgements by the lay public that may, at first glance,
      seem irrational can often be understood when the heuristics, biases, and models
      of human judgements of risk are considered. Risk perception research suggests
      that how lay people perceive risk has less to do with the unidimensional view of
      risk as a probabilistic expression and more to do with a complex multidimensional
      construct in which affect, reason, worldviews, trust, and other factors are
      intertwined. This review summarizes some of the principles of risk perception as
      applicable to transfusion medicine.

PMID- 16565027
TI  - Transfusion-transmitted Klebsiella pneumoniae fatalities, 1995 to 2004.
AB  - Transfusion-transmitted bacterial sepsis is the third most common cause of
      transfusion-related fatalities reported to the Food and Drug Administration.
      Between October 1, 1995, and September 30, 2004, there were 665 reported
      transfusion fatalities. Eighty-five (13%) deaths were due to transfusion
      transmitted bacterial infections, of which 58 (68%) were due to gram-negative
      organisms. The most common gram-negative organism associated with transfusion
      transmitted deaths after receipt of platelets was Klebsiella pneumoniae. This
      article summarizes retrospectively the case series of deaths due to transfusion
      transmitted K pneumoniae infection, reported to the Food and Drug Administration,
      1995 to 2004. There were 12 deaths due to transfusion-transmitted K pneumoniae
      infection with 7 (58%) of the 12 cases occurring in 2002. Eleven deaths were
      caused by the transfusion of contaminated platelets and 1 death attributed to
      contaminated red blood cells. Extensive review of the seven 2002 fatality reports
      did not identify a common (shared) lot for items used during collection or
      processing of the blood product. In conclusion, in cases of suspected transfusion
      transmitted septicemia, broad spectrum antibiotic coverage including coverage of
      gram-negative organisms should be considered. Strict adherence to infection
      control measures while collecting, processing, and handling all blood and blood
      components in both the clinical settings and in the laboratory should be
      followed. Further development of simple and effective test procedures for
      detecting bacteria in the blood is needed.

PMID- 16565028
TI  - The new generation of platelet additive solution for storage at 22 degrees C:
      development and current experience.
AB  - The storage of platelets (PLTs) in PLT additive solutions (PASs) might have
      several advantages. It can reduce allergic and febrile transfusion reactions,
      facilitate AB0-incompatible PLT transfusions, enable pathogen inactivation, and
      make more plasma available for other purposes (eg, for fractionation). For this
      reason, there has been considerable focus on the development of new PASs that
      assure maintenance of good PLT quality throughout storage. Several compounds in
      PASs such as citrate, acetate, phosphate, potassium, and magnesium have all
      turned out to be important, and the same applies to the necessary amount of
      glucose as determined by the plasma carryover. The latest generation of PASs, the
      modified PAS-III and Composol-PS, contains most or all of those compounds.
      Recently published data on the in vitro quality of either buffy coat- or
      apheresis-derived PLT concentrates stored in 70% or even 80% of PAS might
      encourage transfusion specialists to consider using these PASs in routine blood
      banking. However, because in vitro tests do not adequately predict clinical
      effectiveness of PLTs after transfusion, in vivo studies are still needed to
      assess the quality of PAS-stored PLTs.

PMID- 16565029
TI  - Elmer L. DeGowin, MD: blood transfusions in war and peace.
AB  - Elmer L. DeGowin, MD, like many of the pioneers of American blood banking and
      transfusion medicine, entered the discipline because of scientific curiosity and
      a desire to provide efficacious and safe allogeneic transfusions to patients.
      Much of the early impetus and financial support were fueled by the military needs
      of World War II. Dr. DeGowin and his colleagues provided important information
      pertaining to the preservation, storage, transportation, and transfusion of
      blood. After the war, many of these investigations continued and were applied to
      civilian practices. The legacy of Dr. DeGowin to provide exemplary service,
      teaching, and research has been sustained by the physicians and staff of the
      Elmer L. DeGowin Memorial Blood Center (University of Iowa Hospitals and Clinics,
      Iowa City, Ia).

PMID- 16565030
TI  - Do dialogues about concepts of pain reduce immigrant patients' reported spread of
      pain? A comparison between two consultation methods in primary care.
AB  - OBJECTIVES: Do dialogues about concepts of pain reduce the reported spread of
      pain more than the usual consultations? SETTING: A 4-week programme in primary
      care for immigrants on sick-leave, aged 16-45 years, containing daily exercises
      and randomised to either four interviews and dialogues about pain with a female
      doctor (group A) or the usual consultations with a male doctor (group B).
      METHODS: Two doctors made the first and the last evaluations (before and after
      the programme) containing diagnostics of tender-structure locations and
      depression (yes-no), and ratings of severity of psychosocial stressors. Anxiety
      about pain was noted (yes-no). The patients pointed to their painful areas and
      these were noted on pain drawings (0-18 fields). Median values were calculated,
      and non-parametric statistics were used to test for significant differences
      between groups and before-and-after values, and the correlation between the
      number of pain drawing fields and clinical variables. RESULTS: Forty-five persons
      participated in the whole programme, Group A (8 men, 15 women), group B (7 men,
      15 women). Many of them needed an interpreter. Participants in group A had more
      tender-structure locations (two vs. one in group B). Nearly half had depression
      and two-thirds had serious psychosocial stressors. Almost all reported anxiety
      about pain at the start, but afterwards significantly fewer in group A (22 vs.
      16, p < 0.05). In both groups, the number of pain drawing fields decreased
      significantly from, in median, eight to four (p < 0.001), particularly among the
      women (A: p < 0.05 vs. B: p < 0.01). Some very distressed participants reported
      more spread of pain than at the start. Reduced spread of pain was not
      significantly correlated to any clinical variable. CONCLUSIONS: Particularly the
      women in both consultation groups demonstrated much less spread of pain after
      treatment, despite similar clinical findings and less anxiety about pain in group
      A. The initially wide spread of pain may thus have been a way of communicating
      with the doctors.

PMID- 16565031
TI  - The treatment of anomia using errorless learning.
AB  - In the contemporary literature, errorless learning is thought to have benefits
      over more traditional trial-and-error methods. The most prominent investigations
      of errorless learning are those designed for rehabilitation of severe memory
      impairments, including numerous demonstrations of effective amelioration of word
      finding difficulties (Baddeley & Wilson, 1994; Clare, Wilson, Breen, & Hodges,
      1999; Clare et al., 2000; Evans et al., 2000). Despite this, there are very few
      reports on the application of purely errorless learning to people with aphasia
      (Fillingham, Hodgson, Sage, & Lambon Ralph, 2003). The aim of this study was to
      compare directly the efficacy of errorless and errorful learning in a case series
      of 11 aphasic people with pronounced word-finding difficulties. Previous studies
      of errorless learning and, more recently, studies of rehabilitation have
      suggested that cognition is an important factor for determining outcome (Helm
      Estabrooks, 2002; Robertson & Murre, 1999). Therefore, a thorough language and
      neuropsychological assessment battery was completed with each participant. Naming
      therapy was carried out to contrast errorless and errorful therapy in a case
      series analysis. Errorless learning proved to be as effective as the more
      traditional, errorful approach in the majority of cases in terms of both
      immediate improvement and at follow up assessment. Without exception, the
      patients preferred the errorless learning therapy. Strikingly, it was found that
      language skill did not predict therapy outcome. Participants who responded better
      overall, had better recognition memory, executive/problem solving skills and
      monitoring ability. This replicates recent findings that frontal executive skills
      are crucial for rehabilitation (Robertson & Murre, 1999). Also, participants who
      did better at errorful treatment were those with the best working and recall
      memory, and attention. It is probable that these factors are essential cognitive
      components for providing effective monitoring and feedback systems to a more
      general learning mechanism.

PMID- 16565032
TI  - The use of memorised verbal scripts in the rehabilitation of action
      disorganisation syndrome.
AB  - We report data on the rehabilitation of action disorganisation syndrome (ADS).
      Although prior attempts to rehabilitate everyday actions in our patient, FK, had
      proved unsuccessful, we report positive results from using a verbalisation
      strategy. FK was taught a poem based on the steps involved in making a cup of
      tea. Following training, the everyday action was performed more successfully than
      prior to training, with the order of the actions in particular being improved
      when the poem was applied. In addition, there was evidence of error monitoring
      being carried out contingent on the verbalisation strategy. Across training
      sessions FK also became more likely to apply the poem and to perform the actions
      without prompting. However, there was relatively weak training effects across
      sessions, and the beneficial effects did not transfer to new tasks or to the same
      task with a different key object. The utility of the approach for severe cases of
      ADS is discussed.

PMID- 16565033
TI  - Measuring awareness in people with mild to moderate Alzheimer's disease:
      development of the Memory Awareness Rating Scale--adjusted.
AB  - Variations in level of awareness among people with Alzheimer's disease (AD) may
      impact on well-being for the person with dementia and their carer, and may
      influence outcomes of cognitive rehabilitation interventions. Awareness has often
      been assessed using discrepancies between self and proxy rating or between self
      rating and objective task performance, with the latter considered to be
      preferable. Measures are available that are suitable for people with mild AD, for
      example the Memory Awareness Rating Scale (MARS). However, these may be less
      appropriate for people whose impairments are more advanced and who consequently
      have more difficulty with the objective task component. In order to provide a
      measure suitable for people with moderate AD, an adjusted Memory Awareness Rating
      Scale (MARSA) was developed by altering the objective task component of the MARS.
      The MARSA was piloted with 41 participants with mild to moderate AD. It was found
      to be suitable for use with a broader group of participants than the MARS. The
      component ratings were found to have good internal consistency. The component
      ratings and the two indices of awareness had high test-retest reliability. The
      extension of the original measure offers the opportunity to consider awareness
      throughout the course of the disease and provides a basis for longitudinal
      investigations of awareness.

PMID- 16565034
TI  - Effects of visual hemisphere-specific stimulation versus reading-focused training
      in dyslexic children.
AB  - Two groups of children with developmental dyslexia were treated over a period of
      four months. Fourteen children received visual hemisphere-specific stimulation
      (VHSS) and 11 children were treated with a customary, reading-focused training
      programme (RT). Reading performance was investigated before and after treatment,
      as were spelling abilities, phonemic awareness and verbal memory. Improvement in
      reading accuracy was significantly greater in the VHSS group than in the RT
      group. Significant improvements were also observed for memory and phonemic
      skills. The results were compared to existing data on spontaneous reading
      development. The better results after single-hemisphere stimulation (VHSS) are
      discussed in terms of the specific characteristics of the treatment, and of the
      possible contributions of visual-spatial attention, memory functions and phonemic
      awareness.

PMID- 16565035
TI  - Transfer of training effects in stroke patients with apraxia: an exploratory
      study.
AB  - The goal of the present study was to examine the transfer of the effects of
      cognitive strategy training for stroke patients with apraxia from trained to non
      trained tasks. In strategy training, the occurrence of transfer is expected as
      the training programme is aimed, not at relearning specific tasks, but at
      teaching patients new ways to handle the problems resulting from the impairment.
      Exploratory analyses were conducted on data previously collected in a randomised
      controlled trial on the efficacy of the strategy training. A total of 113 left
      hemisphere stroke patients were randomly assigned to a strategy training group
      and a group receiving occupational therapy as usual. Assessment of apraxia, motor
      functioning and activities of daily living (ADL) took place at baseline, after an
      eight-week treatment period, and five months after baseline. The primary outcome
      measure consisted of standardised ADL observations of trained and non-trained
      tasks. The analyses showed that in both treatment groups, the scores on the ADL
      observations for non-trained tasks improved significantly after eight weeks of
      training as compared with the baseline score. Change scores of non-trained
      activities were larger in the strategy training group as compared with the usual
      treatment group. By using previously collected data we are able to illustrate the
      potential transfer of treatment effects in a large sample of stroke patients. We
      found indications for the occurrence of transfer, although the study was not
      originally designed for the purpose of evaluating transfer. Therefore these
      results are worth exploring more profoundly. We will further investigate our
      preliminary conclusions in a new prospective study which is specifically designed
      to examine the transfer of training effects.

PMID- 16565036
TI  - Flooding treatment of phobia to having her feet touched by physiotherapists, in a
      young woman with Down's syndrome and a traumatic brain injury.
AB  - This case study describes the treatment of a 32-year-old woman with Down's
      syndrome and a recent head injury, for phobia to treatment of her feet by
      physiotherapists. The phobia had the potential to severely limit rehabilitation
      progress in terms of the client regaining the ability to stand, assist with
      transfers (including to and from a car), and walk. A single session, in vivo,
      flooding intervention was used. The treatment resulted in a substantial change in
      tolerance of physiotherapists' touching of feet to the extent rehabilitation was
      able to proceed within the bounds of expectation had a phobia not been evident.
      Benefits were maintained at multiple follow-ups. The results of the case study
      extend the evidence for the utility of such behavioural interventions to people
      with complex disability and unusual phobias in neurological rehabilitation
      systems.

PMID- 16565038
TI  - Theory of spatial patterns of intracellular organelles.
AB  - Here we report on a generalized theory of spatial patterns of intracellular
      organelles, which are controlled by cells using cytoskeleton-based movements
      powered by molecular motors. The theory reveals that organelles exhibit one of
      the four distinct, stable patterns, namely aggregation, hyperdispersion, radial
      dispersion, and areal dispersion. Existence of specific patterns is determined by
      the contributions from three transport mechanisms, characterized by two Peclet
      numbers. The predicted patterns compare well with experimental data. This study
      provides a firm theoretical ground for classification of spatial patterns of
      organelles and understanding their regulation by cells.

PMID- 16565039
TI  - Unraveling membrane-mediated substrate-transporter interactions.

PMID- 16565040
TI  - Macromolecular size-and-shape distributions by sedimentation velocity analytical
      ultracentrifugation.
AB  - Sedimentation velocity analytical ultracentrifugation is an important tool in the
      characterization of macromolecules and nanoparticles in solution. The
      sedimentation coefficient distribution c(s) of Lamm equation solutions is based
      on the approximation of a single, weight-average frictional coefficient of all
      particles, determined from the experimental data, which scales the diffusion
      coefficient to the sedimentation coefficient consistent with the traditional s
      approximately M(2/3) power law. It provides a high hydrodynamic resolution, where
      diffusional broadening of the sedimentation boundaries is deconvoluted from the
      sedimentation coefficient distribution. The approximation of a single weight
      average frictional ratio is favored by several experimental factors, and usually
      gives good results for chemically not too dissimilar macromolecules, such as
      mixtures of folded proteins. In this communication, we examine an extension to a
      two-dimensional distribution of sedimentation coefficient and frictional ratio,
      c(s,f(r)), which is representative of a more general set of size-and-shape
      distributions, including mass-Stokes radius distributions, c(M,R(S)), and
      sedimentation coefficient-molar mass distributions c(s,M). We show that this can
      be used to determine average molar masses of macromolecules and characterize
      macromolecular distributions, without the approximation of any scaling
      relationship between hydrodynamic and thermodynamic parameters.

PMID- 16565041
TI  - Effects of ceramide on liquid-ordered domains investigated by simultaneous AFM
      and FCS.
AB  - The sphingolipid ceramides are known to influence lipid lateral organization in
      biological membranes. In particular, ceramide-induced alterations of microdomains
      can be involved in several cell functions, ranging from apoptosis to immune
      response. We used a combined approach of atomic force microscopy, fluorescence
      correlation spectroscopy, and confocal fluorescence imaging to investigate the
      effects of ceramides in model membranes of biological relevance. Our results show
      that physiological quantities of ceramide in
      sphingomyelin/dioleoylphosphatidylcholine/cholesterol supported bilayers lead to
      a significant rearrangement of lipid lateral organization. Our experimental setup
      allowed a simultaneous characterization of both structural and dynamic
      modification of membrane microdomains, induced by the presence of ceramide.
      Formation of similar ceramide-enriched domains and, more general, alterations of
      lipid-lipid interactions can be of crucial importance for the biological function
      of cell membranes.

PMID- 16565042
TI  - Three-dimensional modeling of mechanical forces in the extracellular matrix
      during epithelial lumen formation.
AB  - Mechanical interactions between cells and extracellular matrix (ECM) mediate
      epithelial cyst formation. This work relies on the combination of numerical
      modeling with live cell imaging, to piece together a novel nonintrusive method
      for determining three-dimensional (3D) mechanical forces caused by shape changes
      of a multicellular aggregate at the early stages of epithelial cyst formation. We
      analyzed the evolution of Madin-Darby canine kidney cells in 3D cultures using
      time-lapse microscopy, with type I collagen gel forming the ECM. The evolving 3D
      interface between the ECM and the cell aggregate was obtained from microscopy
      images, and the stress on the surface of a proliferating aggregate and in the
      surrounding ECM was calculated using the finite element method. The viscoelastic
      properties of the ECM (a needed input for the finite element method solver) were
      obtained through oscillatory shear flow experiments on a rheometer. For
      validation purpose, the forces exerted by an aggregate on a force-sensor array
      were measured and compared against the computational results.

PMID- 16565043
TI  - An anion antiporter model of prestin, the outer hair cell motor protein.
AB  - Cochlear amplification in mammalian hearing relies on an active mechanical
      feedback process generated by outer hair cells, driven by a protein, prestin
      (SLC26A5), in the lateral membrane. We have used kinetic models to understand the
      mechanism by which prestin might function. We show that the two previous
      hypotheses of prestin, which assume prestin cannot operate as a transporter, are
      insufficient to explain previously published data. We propose an alternative
      model of prestin as an electrogenic anion exchanger, exchanging one Cl(-) ion for
      one divalent or two monovalent anions. This model can reproduce the key aspects
      of previous experimental observations. The experimentally observed charge
      movements are produced by the translocation of one Cl(-) ion combined with
      intrinsic positively charged residues, while the transport of the counteranion is
      electroneutral. We tested the model with measurements of the Cl(-) dependence of
      charge movement, using SO(4)(2-) to replace Cl(-). The data was compatible with
      the predictions of the model, suggesting that prestin does indeed function as a
      transporter.

PMID- 16565044
TI  - Galactosylceramide domain microstructure: impact of cholesterol and
      nucleation/growth conditions.
AB  - Galactosylceramide (GalCer), a glycosphingolipid, is believed to exist in the
      extracellular leaflet of cell membranes in nanometer-sized domains or rafts. The
      local clustering of GalCer within rafts is thought to facilitate the initial
      adhesion of certain viruses, including HIV-1, and bacteria to cells through
      multivalent interactions between receptor proteins (gp120 for HIV-1) and GalCer.
      Here we use atomic force microscopy (AFM) to study the effects of cholesterol on
      solid-phase GalCer domain microstructure and miscibility with a fluid lipid 1,2
      dilauroyl-sn-glycero-3-phosphocholine (DLPC) in supported lipid bilayers. Using
      "slow-cooled vesicle fusion" to prepare the supported lipid bilayers, we were
      able to overcome the nonequilibrium effects of the substrate (verified by
      comparison to results for giant unilamellar vesicles) and accurately quantify the
      dramatic effect of cholesterol on the GalCer domain surface area/perimeter ratio
      (A(D)/P) and DLPC-GalCer miscibility. We compare these results to a supported
      lipid bilayer system in which the bilayer is rapidly cooled (nonequilibrium
      conditions), "quenched vesicle fusion", and find that the microstructures are
      remarkably similar above a cholesterol mol fraction of approximately 0.06. We
      determined that GalCer domains were contained in one leaflet distal to the mica
      substrate through qualitative binding experiments with Trichosanthes kirilowii
      agglutinin (TKA), a galactose-specific lectin, and AFM of Langmuir-Blodgett
      deposited GalCer/DLPC supported lipid bilayers. In addition, GalCer domains in
      bilayers containing cholesterol rearranged upon tip-sample contact. Our results
      further serve to clarify why discrepancies exist between different model membrane
      systems and between model membranes and cell membranes. In addition, these
      results offer new insight into the effect of cholesterol and surrounding lipid on
      domain microstructure and behavior. Finally, our observations may be pertinent to
      cell membrane structure, dynamics, and HIV infection.

PMID- 16565046
TI  - Modeling protein conformational changes by iterative fitting of distance
      constraints using reoriented normal modes.
AB  - Recently we have developed a normal-modes-based algorithm that predicts the
      direction of protein conformational changes given the initial state crystal
      structure together with a small number of pairwise distance constraints for the
      end state. Here we significantly extend this method to accurately model both the
      direction and amplitude of protein conformational changes. The new protocol
      implements a multisteps search in the conformational space that is driven by
      iteratively minimizing the error of fitting the given distance constraints and
      simultaneously enforcing the restraint of low elastic energy. At each step, an
      incremental structural displacement is computed as a linear combination of the
      lowest 10 normal modes derived from an elastic network model, whose eigenvectors
      are reorientated to correct for the distortions caused by the structural
      displacements in the previous steps. We test this method on a list of 16 pairs of
      protein structures for which relatively large conformational changes are observed
      (root mean square deviation >3 angstroms), using up to 10 pairwise distance
      constraints selected by a fluctuation analysis of the initial state structures.
      This method has achieved a near-optimal performance in almost all cases, and in
      many cases the final structural models lie within root mean square deviation of 1
      approximately 2 angstroms from the native end state structures.

PMID- 16565045
TI  - Coexisting domains in the plasma membranes of live cells characterized by spin
      label ESR spectroscopy.
AB  - The importance of membrane-based compartmentalization in eukaryotic cell function
      has become broadly appreciated, and a number of studies indicate that these
      eukaryotic cell membranes contain coexisting liquid-ordered (L(o)) and liquid
      disordered (L(d)) lipid domains. However, the current evidence for such phase
      separation is indirect, and so far there has been no direct demonstration of
      differences in the ordering and dynamics for the lipids in these two types of
      regions or their relative amounts in the plasma membranes of live cells. In this
      study, we provide direct evidence for the presence of two different types of
      lipid populations in the plasma membranes of live cells from four different cell
      lines by electron spin resonance. Analysis of the electron spin resonance spectra
      recorded over a range of temperatures, from 5 to 37 degrees C, shows that the
      spin-labeled phospholipids incorporated experience two types of environments,
      L(o) and L(d), with distinct order parameters and rotational diffusion
      coefficients but with some differences among the four cell lines. These results
      suggest that coexistence of lipid domains that differ significantly in their
      dynamic order in the plasma membrane is a general phenomenon. The L(o) region is
      found to be a major component in contrast to a model in which small liquid
      ordered lipid rafts exist in a 'sea' of disordered lipids. The results on
      ordering and dynamics for the live cells are also compared with those from model
      membranes exhibiting coexisting L(o) and L(d) phases.

PMID- 16565047
TI  - Ultrafast carotenoid-to-chlorophyll singlet energy transfer in the cytochrome b6f
      complex from Bryopsis corticulans.
AB  - Ultrafast carotenoid-to-chlorophyll (Car-to-Chl) singlet excitation energy
      transfer in the cytochrome b(6)f (Cyt b(6)f) complex from Bryopsis corticulans is
      investigated by the use of femtosecond time-resolved absorption spectroscopy. For
      all-trans-alpha-carotene free in n-hexane, the lifetimes of the two low-lying
      singlet excited states, S(1)(2A(g)(-)) and S(2)(1B(u)(+)), are determined to be
      14.3 +/- 0.4 ps and 230 +/- 10 fs, respectively. For the Cyt b(6)f complex, to
      which 9-cis-alpha-carotene is bound, the lifetime of the S(1)(2A(g)(-)) state
      remains unchanged, whereas that of the S(2)(1B(u)(+)) state is significantly
      reduced. In addition, a decay-to-rise correlation between the excited-state
      dynamics of alpha-carotene and Chl a is clearly observed. This spectroscopic
      evidence proves that the S(2)(1B(u)(+)) state is able to transfer electronic
      excitations to the Q(x) state of Chl a, whereas the S(1)(2A(g)(-)) state remains
      inactive. The time constant and the partial efficiency of the energy transfer are
      determined to be 240 +/- 40 fs and (49 +/- 4)%, respectively, which supports the
      overall efficiency of 24% determined with steady-state fluorescence spectroscopy.
      A scheme of the alpha-carotene-to-Chl a singlet energy transfer is proposed based
      on the excited-state dynamics of the pigments.

PMID- 16565048
TI  - Uncoupling store-operated Ca2+ entry and altered Ca2+ release from sarcoplasmic
      reticulum through silencing of junctophilin genes.
AB  - Junctophilin (JP) mediates the close contact between cell surface and
      intracellular membranes in muscle cells ensuring efficient excitation-contraction
      coupling. Here we demonstrate that disruption of triad junction structure formed
      by the transverse tubular (TT) invagination of plasma membrane and terminal
      cisternae of sarcoplasmic reticulum (SR) by reduction of JP expression leads to
      defective Ca2+ homeostasis in muscle cells. Using adenovirus with small hairpin
      interference RNA (shRNA) against both JP1 and JP2 genes, we could achieve acute
      suppression of JPs in skeletal muscle fibers. The shRNA-treated muscles exhibit
      deformed triad junctions and reduced store-operated Ca2+ entry (SOCE), which is
      likely due to uncoupled retrograde signaling from SR to TT. Knockdown of JP also
      causes a reduction in SR Ca2+ storage and altered caffeine-induced Ca2+ release,
      suggesting an orthograde regulation of the TT membrane on the SR Ca2+ release
      machinery. Our data demonstrate that JPs play an important role in controlling
      overall intracellular Ca2+ homeostasis in muscle cells. We speculate that altered
      expression of JPs may underlie some of the phenotypic changes associated with
      certain muscle diseases and aging.

PMID- 16565049
TI  - Two-dimensional infrared spectroscopy displays signatures of structural ordering
      in peptide aggregates.
AB  - In the presence of lipid bilayers, the hexapeptide AcWL(5) forms membrane-bound
      aggregates dominated by beta-secondary structure and is thus a useful model for
      the onset of peptide aggregation in membrane environments. Two-dimensional
      infrared (2D IR) spectra in the amide I region for aggregates of AcWL(5) peptides
      with single isotopic labels provide new insight into the residue-level structural
      ordering of the aggregated peptides. Separation of spectral information along two
      axes provides clear indications of the band frequencies and relative intensities,
      which together are an indication of extended amide coupling networks across
      structural regions of a particular size. The lowered anharmonicities, relative to
      free peptide, and the narrow, homogeneous lineshapes of the 2D IR peaks indicate
      the delocalization of vibrational modes through an ordered structure whose
      flexibility varies with relative peptide concentration. Crosspeaks between
      delocalized transitions can be used to estimate the strength of the coupling
      interactions between neighboring residues. The sensitivity of 2D IR spectra to
      residue-level structural ordering shows that 2D IR spectroscopy is a powerful
      technique for probing structures formed during the onset of peptide aggregation.

PMID- 16565050
TI  - Quantitative scattering of melanin solutions.
AB  - The optical scattering coefficient of a dilute, well-solubilized eumelanin
      solution has been accurately measured as a function of incident wavelength, and
      found to contribute <6% of the total optical attenuation between 210 and 325 nm.
      At longer wavelengths (325-800 nm), the scattering was less than the minimum
      sensitivity of our instrument. This indicates that ultraviolet and visible
      optical density spectra can be interpreted as true absorption with a high degree
      of confidence. The scattering coefficient versus wavelength was found to be
      consistent with Rayleigh theory for a particle radius of 38 +/- 1 nm. Our results
      shed important light on the role of melanins as photoprotectants.

PMID- 16565051
TI  - Absence of fluid-ordered/fluid-disordered phase coexistence in ceramide/POPC
      mixtures containing cholesterol.
AB  - The effect of temperature on the lateral structure of lipid bilayers composed of
      porcine brain ceramide and 1-palmitoyl 2-oleoyl-phosphatidylcholine (POPC), with
      and without addition of cholesterol, were studied using differential scanning
      calorimetry, Fourier transformed infrared spectroscopy, atomic force microscopy,
      and confocal/two-photon excitation fluorescence microscopy (which included
      LAURDAN generalized polarization function images). A broad gel/fluid phase
      coexistence temperature regime, characterized by the presence of micrometer-sized
      gel-phase domains with stripe and flowerlike shapes, was observed for different
      POPC/ceramide mixtures (up to approximately 25 mol % ceramide). This observed
      phase coexistence scenario is in contrast to that reported previously for this
      mixture, where absence of gel/fluid phase coexistence was claimed using bulk
      LAURDAN generalized polarization (GP) measurements. We demonstrate that this
      apparent discrepancy (based on the direct comparison between the LAURDAN GP data
      obtained in the microscope and the fluorometer) disappears when the additive
      property of the LAURDAN GP function is taken into account to examine the data
      obtained using bulk fluorescence measurements. Addition of cholesterol to the
      POPC/ceramide mixtures shows a gradual transition from a gel/fluid to gel/liquid
      ordered phase coexistence scenario as indicated by the different experimental
      techniques used in our experiments. This last result suggests the absence of
      fluid-ordered/fluid-disordered phase coexistence in the ternary mixtures studied
      in contrast to that observed at similar molar concentrations with other ceramide
      base-containing lipid mixtures (such as POPC/sphingomyelin/cholesterol, which is
      used as a canonical raft model membrane). Additionally, we observe a critical
      cholesterol concentration in the ternary mixtures that generates a peculiar
      lateral pattern characterized by the observation of three distinct regions in the
      membrane.

PMID- 16565052
TI  - Channel density regulation of firing patterns in a cortical neuron model.
AB  - Modifying the density and distribution of ion channels in a neuron (by natural up
      and downregulation or by pharmacological intervention or by spontaneous
      mutations) changes its activity pattern. In this investigation we analyzed how
      the impulse patterns are regulated by the density of voltage-gated channels in a
      neuron model based on voltage-clamp measurements of hippocampal interneurons. At
      least three distinct oscillatory patterns, associated with three distinct regions
      in the Na-K channel density plane, were found. A stability analysis showed that
      the different regions are characterized by saddle-node, double-orbit, and Hopf
      bifurcation threshold dynamics, respectively. Single, strongly graded action
      potentials occur in an area outside the oscillatory regions, but less graded
      action potentials occur together with repetitive firing over a considerable range
      of channel densities. The relationship found here between channel densities and
      oscillatory behavior may partly explain the difference between the principal
      spiking patterns previously described for crab axons (class 1 and 2) and cortical
      neurons (regular firing and fast spiking).

PMID- 16565053
TI  - Energetics and dynamics of constrained actin filament bundling.
AB  - The formation of filopodia-like bundles from a dendritic actin network has been
      observed to occur in vitro as a result of branching induced by Arp2/3 complex. We
      study both the energetics and dynamics of actin filament bundling in such a
      network to evaluate their relative importance in bundle formation processes. Our
      model considers two semiflexible actin filaments fixed at one end and free at the
      other, described using a normal-mode approximation. This model is studied by both
      Brownian dynamics and free-energy minimization methods. Remarkably, even short
      filaments can bundle at separations comparable to their lengths. In the dynamic
      simulations, we evaluate the time required for the filaments to interact and
      bind, and examine the dependence of this bundling time on the filament length,
      the distance between the filament bases, and the cross-linking energy. In most
      cases, bundling occurs in a second or less. Beyond a certain critical distance,
      we find that the bundling time increases very rapidly with increasing
      interfilament separation and/or decreasing filament length. For most of the cases
      we have studied, the energetics results for this critical distance are similar to
      those obtained from dynamics simulations run for 10 s, suggesting that beyond
      this timescale, energetics, rather than kinetic constraints, determine whether or
      not bundling occurs. Over a broad range of conditions, we find that the times
      required for bundling from a network are compatible with experimental
      observations.

PMID- 16565054
TI  - Polymorphic fibril formation by residues 10-40 of the Alzheimer's beta-amyloid
      peptide.
AB  - We report investigations of the morphology and molecular structure of amyloid
      fibrils comprised of residues 10-40 of the Alzheimer's beta-amyloid peptide
      (Abeta(10-40)), prepared under various solution conditions and degrees of
      agitation. Omission of residues 1-9 from the full-length Alzheimer's beta-amyloid
      peptide (Abeta(1-40)) did not prevent the peptide from forming amyloid fibrils or
      eliminate fibril polymorphism. These results are consistent with residues 1-9
      being disordered in Abeta(1-40) fibrils, and show that fibril polymorphism is not
      a consequence of disorder in residues 1-9. Fibril morphology was analyzed by
      atomic force and electron microscopy, and secondary structure and inter-side
      chain proximity were probed using solid-state NMR. Abeta(1-40) fibrils were found
      to be structurally compatible with Abeta(10-40): Abeta(1-40) fibril fragments
      were used to seed the growth of Abeta(10-40) fibrils, with propagation of fibril
      morphology and molecular structure. In addition, comparison of lyophilized and
      hydrated fibril samples revealed no effect of hydration on molecular structure,
      indicating that Abeta(10-40) fibrils are unlikely to contain bulk water.

PMID- 16565055
TI  - Dynamic pathways for viral capsid assembly.
AB  - We develop a class of models with which we simulate the assembly of particles
      into T1 capsidlike objects using Newtonian dynamics. By simulating assembly for
      many different values of system parameters, we vary the forces that drive
      assembly. For some ranges of parameters, assembly is facile; for others, assembly
      is dynamically frustrated by kinetic traps corresponding to malformed or
      incompletely formed capsids. Our simulations sample many independent trajectories
      at various capsomer concentrations, allowing for statistically meaningful
      conclusions. Depending on subunit (i.e., capsomer) geometries, successful
      assembly proceeds by several mechanisms involving binding of intermediates of
      various sizes. We discuss the relationship between these mechanisms and
      experimental evaluations of capsid assembly processes.

PMID- 16565056
TI  - Receptor-receptor coupling in bacterial chemotaxis: evidence for strongly coupled
      clusters.
AB  - Receptor coupling is believed to explain the high sensitivity of the Escherichia
      coli chemotaxis network to small changes in levels of chemoattractant. We compare
      in detail the activity response of coupled two-state receptors for different
      models of receptor coupling: weakly-coupled extended one-dimensional and two
      dimensional lattice models and the Monod-Wyman-Changeux model of isolated
      strongly-coupled clusters. We identify features in recent data that distinguish
      between the models. Specifically, researchers have measured the receptor activity
      response to steps of chemoattractant for a variety of engineered E. coli strains
      using in vivo fluorescence resonance energy transfer. We find that the
      fluorescence resonance energy transfer results for wild-type and for a low
      activity mutant are inconsistent with the lattice models of receptor coupling,
      but consistent with the Monod-Wyman-Changeux model of receptor coupling,
      suggesting that receptors form isolated strongly-coupled clusters.

PMID- 16565057
TI  - Side-chain interactions determine amyloid formation by model polyglutamine
      peptides in molecular dynamics simulations.
AB  - The pathological manifestation of nine hereditary neurodegenerative diseases is
      the presence within the brain of aggregates of disease-specific proteins that
      contain polyglutamine tracts longer than a critical length. To improve our
      understanding of the processes by which polyglutamine-containing proteins misfold
      and aggregate, we have conducted molecular dynamics simulations of the
      aggregation of model polyglutamine peptides. This work was accomplished by
      extending the PRIME model to polyglutamine. PRIME is an off-lattice, unbiased,
      intermediate-resolution protein model based on an amino acid representation of
      between three and seven united atoms, depending on the residue being modeled. The
      effects of hydrophobicity on the system are studied by varying the strength of
      the hydrophobic interaction from 12.5% to 5% of the hydrogen-bonding interaction
      strength. In our simulations, we observe the spontaneous formation of aggregates
      and annular structures that are made up of beta-sheets starting from random
      configurations of random coils. This result was interesting because tubular
      protofibrils were recently found in experiments on polyglutamine aggregation and
      because of Perutz's prediction that polyglutamine would form water-filled
      nanotubes.

PMID- 16565058
TI  - A biopolymer transistor: electrical amplification by microtubules.
AB  - Microtubules (MTs) are important cytoskeletal structures engaged in a number of
      specific cellular activities, including vesicular traffic, cell cyto-architecture
      and motility, cell division, and information processing within neuronal
      processes. MTs have also been implicated in higher neuronal functions, including
      memory and the emergence of "consciousness". How MTs handle and process
      electrical information, however, is heretofore unknown. Here we show new
      electrodynamic properties of MTs. Isolated, taxol-stabilized MTs behave as
      biomolecular transistors capable of amplifying electrical information. Electrical
      amplification by MTs can lead to the enhancement of dynamic information, and
      processivity in neurons can be conceptualized as an "ionic-based" transistor,
      which may affect, among other known functions, neuronal computational
      capabilities.

PMID- 16565059
TI  - Swelling-activated pathways in human T-lymphocytes studied by cell volumetry and
      electrorotation.
AB  - Small organic solutes, including sugar derivatives, amino acids, etc., contribute
      significantly to the osmoregulation of mammalian cells. The present study
      explores the mechanisms of swelling-activated membrane permeability for
      electrolytes and neutral carbohydrates in Jurkat cells. Electrorotation was used
      to analyze the relationship between the hypotonically induced changes in the
      electrically accessible surface area of the plasma membrane (probed by the
      capacitance) and its permeability to the monomeric sugar alcohol sorbitol, the
      disaccharide trehalose, and electrolyte. Time-resolved capacitance and volumetric
      measurements were performed in parallel using media of different osmolalities
      containing either sorbitol or trehalose as the major solute. Under mild hypotonic
      stress in 200 mOsm sorbitol or trehalose solutions, the cells accomplished
      regulatory volume decrease by releasing cytosolic electrolytes presumably through
      pathways activated by the swelling-mediated retraction of microvilli. This is
      suggested by a rapid decrease of the area-specific membrane capacitance C(m)
      (microF/cm2). The cell membrane was impermeable to both carbohydrates in 200 mOsm
      media. Whereas trehalose permeability remained also very poor in 100 mOsm medium,
      extreme swelling of cells in a strongly hypotonic solution (100 mOsm) led to a
      dramatic increase in sorbitol permeability as evidenced by regulatory volume
      decrease inhibition. The different osmotic thresholds for activation of
      electrolyte release and sorbitol influx suggest the involvement of separate
      swelling-activated pathways. Whereas the electrolyte efflux seemed to utilize
      pathways preexisting in the plasma membrane, putative sorbitol channels might be
      inserted into the membrane from cytosolic vesicles via swelling-mediated
      exocytosis, as indicated by a substantial increase in the whole-cell capacitance
      C(C) (pF) in strongly hypotonic solutions.

PMID- 16565060
TI  - The effect of salt on self-assembled actin-lysozyme complexes.
AB  - We present a combined experimental and computational study of the bundling of F
      actin filaments induced by lysozyme proteins. Synchrotron small-angle x-ray
      scattering results show that these bundles consist of close-packed columnar
      complexes in which the actin is held together by incommensurate, one-dimensional
      arrays of lysozyme macroions. Molecular dynamics simulations of a coarse-grained
      model confirm the arrangement of the lysozyme and the stability of this
      structure. In addition, we find that these complexes remain stable even in the
      presence of significant concentrations of monovalent salt. The simulations show
      that this arises from partitioning of the salt between the aqueous and the
      condensed phases. The osmotic pressure resulting from the excess concentration of
      the salt in the aqueous phase balances the osmotic pressure increase in the
      bundle. These results are relevant for a variety of biological and biomedical
      problems in which electrostatic complexation between anionic polyelectrolytes and
      cationic globular proteins takes place, such as the pathological self-assembly of
      endogenous antibiotic polypeptides and inflammatory polymers in cystic fibrosis.

PMID- 16565062
TI  - Closed-loop miscibility gap and quantitative tie-lines in ternary membranes
      containing diphytanoyl PC.
AB  - Vesicles containing ternary mixtures of diphytanoylphosphatidylcholine,
      dipalmitoylphosphatidylcholine (DPPC), and cholesterol produce coexisting liquid
      phases over an unusually large range of temperature and composition. Liquid
      domains persist well above the DPPC chain melting temperature (41 degrees C),
      resulting in a closed-loop miscibility gap bounded by two critical points at
      fixed temperature. Quantitative tie-lines are determined directly from 2H NMR
      spectra using a novel analysis, and are found to connect a liquid-disordered
      phase rich in diphytanoyl PC with a liquid-ordered phase rich in DPPC. The
      direction of the tie-lines implies that binary DPPC/cholesterol mixtures are in
      one uniform phase above 41 degrees C. All 2H NMR results for tie-lines are
      verified by independent fluorescence microscopy results.

PMID- 16565061
TI  - Interaction of transported drugs with the lipid bilayer and P-glycoprotein
      through a solvation exchange mechanism.
AB  - Broad substrate specificity of human P-glycoprotein (ABCB1) is an essential
      feature of multidrug resistance. Transport substrates of P-glycoprotein are
      mostly hydrophobic and many of them have net positive charge. These compounds
      partition into the membrane. Utilizing the energy of ATP hydrolysis, P
      glycoprotein is thought to take up substrates from the cytoplasmic leaflet of the
      plasma membrane and to transport them to the outside of the cell. We examined
      this model by molecular dynamics simulation of the lipid bilayer, in the presence
      of transport substrates together with an atomic resolution structural model of P
      glycoprotein. Taken together with previous electron paramagnetic resonance
      studies, the results suggest that most transported drugs are concentrated near
      the surface zone of the inner leaflet of the plasma membrane. Here the drugs can
      easily diffuse laterally into the drug-binding site of P-glycoprotein through an
      open cleft. It was concluded that the initial high-affinity drug-binding site was
      located in the interfacial surface area of P-glycoprotein in contact with the
      membrane interface. Based on these results and our recent kinetic studies, a
      "solvation exchange" drug transport mechanism of P-glycoprotein is discussed. A
      molecular basis for the improved colchicine transport efficiency by the much
      studied colchicine-resistance G185V mutant human P-glycoprotein is also provided.

PMID- 16565063
TI  - Computer modeling demonstrates that electrostatic attraction of nucleosomal DNA
      is mediated by histone tails.
AB  - We conducted molecular dynamics computer simulations of charged histone tail-DNA
      interactions in systems mimicking nucleosome core particles (NCP) . In a coarse
      grained model, the NCP is modeled as a negatively charged spherical particle with
      flexible polycationic histone tails attached to it in a dielectric continuum with
      explicit mobile counterions and added salt. The size, charge, and distribution of
      the tails relative to the core were built to mimick real NCP. In this way, we
      incorporate attractive ion-ion correlation effects due to fluctuations in the ion
      cloud and the attractive entropic and energetic tail-bridging effects. In
      agreement with experimental data, increase of monovalent salt content from salt
      free to physiological concentration leads to the formation of NCP aggregates;
      likewise, in the presence of MgCl2, the NCPs form condensed systems via histone
      tail bridging and accumulation of counterions. More detailed mechanisms of the
      histone tail-DNA interactions and dynamics have been obtained from all-atom
      molecular dynamics simulations (including water), comprising three DNA 22-mers
      and 14 short fragments of the H4 histone tail (amino acids 5-12) carrying three
      positive charges on lysine+ interacting with DNA. We found correlation of the DNA
      DNA distance with the presence and association of the histone tail between the
      DNA molecules.

PMID- 16565064
TI  - Cytochrome C interaction with cardiolipin/phosphatidylcholine model membranes:
      effect of cardiolipin protonation.
AB  - Resonance energy transfer between anthrylvinyl-labeled phosphatidylcholine as a
      donor and heme moiety of cytochrome c (cyt c) as an acceptor has been employed to
      explore the protein binding to model membranes, composed of phosphatidylcholine
      and cardiolipin (CL). The existence of two types of protein-lipid complexes has
      been hypothesized where either deprotonated or partially protonated CL molecules
      are responsible for cyt c attachment to bilayer surface. To quantitatively
      describe cyt c membrane binding, the adsorption model based on scaled particle
      and double layer theories has been employed, with potential-dependent association
      constants being treated as a function of acidic phospholipid mole fraction,
      degree of CL protonation, ionic strength, and surface coverage. Multiple arrays
      of resonance energy transfer data obtained under conditions of varying pH, ionic
      strength, CL content, and protein/lipid molar ratio have been analyzed in terms
      of the model of energy transfer in two-dimensional systems combined with the
      adsorption model allowing for area exclusion and electrostatic effects. The set
      of recovered model parameters included effective protein charge, intrinsic
      association constants, and heme distance from the bilayer midplane for both types
      of protein-lipid complexes. Upon increasing CL mole fraction from 10 to 20 mol %
      (the value close to that characteristic of the inner mitochondrial membrane), the
      binding equilibrium dramatically shifted toward cyt c association with partially
      protonated CL species. The estimates of heme distance from bilayer center suggest
      shallow bilayer location of cyt c at physiological pH, whereas at pH below 6.0,
      the protein tends to insert into membrane core.

PMID- 16565065
TI  - In situ fluorescent protein imaging with metal film-enhanced total internal
      reflection microscopy.
AB  - Fluorescence detection of single molecules provides a means to investigate
      protein dynamics minus ambiguities introduced by ensemble averages of
      unsynchronized protein movement or of protein movement mimicking a local
      symmetry. For proteins in a biological assembly, taking advantage of the single
      molecule approach could require single protein isolation from within a high
      protein concentration milieu. Myosin cross-bridges in a muscle fiber are proteins
      attaining concentrations of approximately 120 muM, implying single myosin
      detection volume for this biological assembly is approximately 1 attoL (10(-18)
      L) provided that just 2% of the cross-bridges are fluorescently labeled. With
      total internal reflection microscopy (TIRM) an exponentially decaying
      electromagnetic field established on the surface of a glass-substrate/aqueous
      sample interface defines a subdiffraction limit penetration depth into the sample
      that, when combined with confocal microscopy, permits image formation from
      approximately 3 attoL volumes. Demonstrated here is a variation of TIRM
      incorporating a nanometer scale metal film into the substrate/glass interface.
      Comparison of TIRM images from rhodamine-labeled cross-bridges in muscle fibers
      contacting simultaneously the bare glass and metal-coated interface show the
      metal film noticeably reduces both background fluorescence and the depth into the
      sample from which fluorescence is detected. High contrast metal film-enhanced
      TIRM images allow secondary label visualization in the muscle fibers,
      facilitating elucidation of Z-disk structure. Reduction of both background
      fluorescence and detection depth will enhance TIRM's usefulness for single
      molecule isolation within biological assemblies.

PMID- 16565066
TI  - Scaling behavior in mitochondrial redox fluctuations.
AB  - Scale-invariant long-range correlations have been reported in fluctuations of
      time-series signals originating from diverse processes such as heart beat
      dynamics, earthquakes, and stock market data. The common denominator of these
      apparently different processes is a highly nonlinear dynamics with competing
      forces and distinct feedback species. We report for the first time an
      experimental evidence for scaling behavior in NAD(P)H signal fluctuations in
      isolated mitochondria and intact cells isolated from the liver of a young (5
      month-old) mouse. Time-series data were collected by two-photon imaging of
      mitochondrial NAD(P)H fluorescence and signal fluctuations were quantitatively
      analyzed for statistical correlations by detrended fluctuation analysis and
      spectral power analysis. Redox [NAD(P)H / NAD(P)(+)] fluctuations in isolated
      mitochondria and intact liver cells were found to display nonrandom, long-range
      correlations. These correlations are interpreted as arising due to the regulatory
      dynamics operative in Krebs' cycle enzyme network and electron transport chain in
      the mitochondria. This finding may provide a novel basis for understanding
      similar regulatory networks that govern the nonequilibrium properties of living
      cells.

PMID- 16565068
TI  - Mismatches and bubbles in DNA.
AB  - Single mismatches in the DNA double helix form nucleation sites for bubbles.
      Although the overall melting temperature of the duplex is affected to different
      degrees depending on the probe length, the statistical weights of the bubble
      states around the defect are always strongly affected. Here we show
      experimentally that a single mismatch has indeed a dramatic effect on the
      distribution of intermediate (bubble) states in the melting transition of DNA
      oligomers. For probe lengths in the range 20-40 bases, the mismatch transforms a
      transition with many intermediates into a nearly two-state transition. One
      surprising consequence is the existence of a regime where the sensitivity of a
      mismatch detection assay based on monitoring intermediate states would increase
      with probe length. Our results provide experimental constraints on how mismatches
      should be implemented in models of DNA melting, such as the widely used
      thermodynamic nearest neighbor model, to which we compare our data.

PMID- 16565067
TI  - An evolutionary strategy for all-atom folding of the 60-amino-acid bacterial
      ribosomal protein l20.
AB  - We have investigated an evolutionary algorithm for de novo all-atom folding of
      the bacterial ribosomal protein L20. We report results of two simulations that
      converge to near-native conformations of this 60-amino-acid, four-helix protein.
      We observe a steady increase of "native content" in both simulated ensembles and
      a large number of near-native conformations in their final populations. We argue
      that these structures represent a significant fraction of the low-energy
      metastable conformations, which characterize the folding funnel of this protein.
      These data validate our all-atom free-energy force field PFF01 for tertiary
      structure prediction of a previously inaccessible structural family of proteins.
      We also compare folding simulations of the evolutionary algorithm with the basin
      hopping technique for the Trp-cage protein. We find that the evolutionary
      algorithm generates a dynamic memory in the simulated population, which leads to
      faster overall convergence.

PMID- 16565070
TI  - Gaussian-weighted RMSD superposition of proteins: a structural comparison for
      flexible proteins and predicted protein structures.
AB  - Many proteins contain flexible structures such as loops and hinged domains. A
      simple root mean square deviation (RMSD) alignment of two different conformations
      of the same protein can be skewed by the difference between the mobile regions.
      To overcome this problem, we have developed a novel method to overlay two protein
      conformations by their atomic coordinates using a Gaussian-weighted RMSD (wRMSD)
      fit. The algorithm is based on the Kabsch least-squares method and determines an
      optimal transformation between two molecules by calculating the minimal weighted
      deviation between the two coordinate sets. Unlike other techniques that choose
      subsets of residues to overlay, all atoms are included in the wRMSD overlay.
      Atoms that barely move between the two conformations will have a greater
      weighting than those that have a large displacement. Our superposition tool has
      produced successful alignments when applied to proteins for which two
      conformations are known. The transformation calculation is heavily weighted by
      the coordinates of the static region of the two conformations, highlighting the
      range of flexibility in the overlaid structures. Lastly, we show how wRMSD fits
      can be used to evaluate predicted protein structures. Comparing a predicted fold
      to its experimentally determined target structure is another case of comparing
      two protein conformations of the same sequence, and the degree of alignment
      directly reflects the quality of the prediction.

PMID- 16565071
TI  - Nuclear factor-1-X regulates astrocyte-specific expression of the alpha1
      antichymotrypsin and glial fibrillary acidic protein genes.
AB  - Discrete tissue-specific changes in chromatin structure of the distal serpin
      subcluster on human chromosome 14q32.1 allow a single gene encoding alpha1
      antichymotrypsin (ACT) to be expressed in astrocytes and glioma cells. This
      astrocyte-specific regulation involves activatory protein-1 (AP-1) because
      overexpression of dominant-negative c-jun(TAM67) abolishes ACT expression in
      glioma cells. Here we identify a new regulatory element, located within the -13
      kb enhancer of the ACT gene, that binds nuclear factor-1 (NFI) and is
      indispensable for the full basal transcriptional activity of the ACT gene.
      Furthermore, down-regulation of NFI expression by siRNA abolishes basal ACT
      expression in glioma cells. However, NFI does not mediate astrocyte-specific
      expression by itself, but likely cooperates with AP-1. A detailed analysis of the
      14-kb long 5'-flanking region of the ACT gene indicated the presence of adjacent
      NFI and AP-1 elements that colocalized with DNase I-hypersensitive sites found in
      astrocytes and glioma cells. Interestingly, knock-down of NFI expression also
      specifically abrogates the expression of glial acidic fibrillary protein (GFAP),
      which is an astrocyte-specific marker protein. Mutations introduced into putative
      NFI and AP-1 elements within the 5'-flanking region of the GFAP gene also
      diminished basal expression of the reporter. In addition, we found, using isoform
      specific siRNAs, that NFI-X regulates the astrocyte-specific expression of ACT
      and GFAP. We propose that NFI-X cooperates with AP-1 by an unknown mechanism in
      astrocytes, which results in the expression of a subset of astrocyte-specific
      genes.

PMID- 16565072
TI  - Major histocompatibility complex and T cell interactions of a universal T cell
      epitope from Plasmodium falciparum circumsporozoite protein.
AB  - A 20-residue sequence from the C-terminal region of the circumsporozoite protein
      of the malaria parasite Plasmodium falciparum is considered a universal helper T
      cell epitope because it is immunogenic in individuals of many major
      histocompatibility complex (MHC) haplotypes. Subunit vaccines containing T* and
      the major B cell epitope of the circumsporozoite protein induce high antibody
      titers to the malaria parasite and significant T cell responses in humans. In
      this study we have evaluated the specificity of the T* sequence with regard to
      its binding to the human class II MHC protein DR4 (HLA-DRB1*0401), its
      interactions with antigen receptors on T cells, and the effect of natural
      variants of this sequence on its immunogenicity. Computational approaches
      identified multiple potential DR4-binding epitopes within T*, and experimental
      binding studies confirmed the following two tight binding epitopes: one located
      toward the N terminus (the T*-1 epitope) and one at the C terminus (the T*-5
      epitope). Immunization of a human DR4 volunteer with a peptide-based vaccine
      containing the T* sequence elicited CD4+ T cells that recognize each of these
      epitopes. Here we present an analysis of the immunodominant N-terminal epitope T*
      1. T*-1 residues important for interaction with DR4 and with antigen receptors on
      T*-specific T cells were mapped. MHC tetramers carrying DR4/T*-1 MHC-peptide
      complexes stained and efficiently stimulated these cells in vitro. T*-1 overlaps
      a region of the protein that has been described as highly polymorphic; however,
      the particular T*-1 residues required for anchoring to DR4 were highly conserved
      in Plasmodium sequences described to date.

PMID- 16565073
TI  - Enolase activates homotypic vacuole fusion and protein transport to the vacuole
      in yeast.
AB  - Membrane fusion and protein trafficking to the vacuole are complex processes
      involving many proteins and lipids. Cytosol from Saccharomyces cerevisiae
      contains a high Mr activity, which stimulates the in vitro homotypic fusion of
      isolated yeast vacuoles. Here we purify this activity and identify it as enolase
      (Eno1p and Eno2p). Enolase is a cytosolic glycolytic enzyme, but a small portion
      of enolase is bound to vacuoles. Recombinant Eno1p or Eno2p stimulates in vitro
      vacuole fusion, as does a catalytically inactive mutant enolase, suggesting a
      role for enolase in fusion that is separate from its glycolytic function. Either
      deletion of the non-essential ENO1 gene or diminished expression of the essential
      ENO2 gene causes vacuole fragmentation in vivo, reflecting reduced fusion.
      Combining an ENO1 deletion with ENO2-deficient expression causes a more severe
      fragmentation phenotype. Vacuoles from enolase 1 and 2-deficient cells are unable
      to fuse in vitro. Immunoblots of vacuoles from wild type and mutant strains
      reveal that enolase deficiency also prevents normal protein sorting to the
      vacuole, exacerbating the fusion defect. Band 3 has been shown to bind glycolytic
      enzymes to membranes of mammalian erythrocytes. Bor1p, the yeast band 3 homolog,
      localizes to the vacuole. Its loss results in the mislocalization of enolase and
      other vacuole fusion proteins. These studies show that enolase stimulates vacuole
      fusion and that enolase and Bor1p regulate selective protein trafficking to the
      vacuole.

PMID- 16565074
TI  - Role of GSH in estrone sulfate binding and translocation by the multidrug
      resistance protein 1 (MRP1/ABCC1).
AB  - Multidrug resistance protein 1 (MRP1/ABCC1) is an ATP-dependent efflux pump that
      can confer resistance to multiple anticancer drugs and transport conjugated
      organic anions. Unusually, transport of several MRP1 substrates requires
      glutathione (GSH). For example, estrone sulfate transport by MRP1 is stimulated
      by GSH, vincristine is co-transported with GSH, or GSH can be transported alone.
      In the present study, radioligand binding assays were developed to investigate
      the mechanistic details of GSH-stimulated transport of estrone sulfate by MRP1.
      We have established that estrone sulfate binding to MRP1 requires GSH, or its non
      reducing analogue S-methyl GSH (S-mGSH), and further that the affinity (Kd) of
      MRP1 for estrone sulfate is 2.5-fold higher in the presence of S-mGSH than GSH
      itself. Association kinetics show that GSH binds to MRP1 first, and we propose
      that GSH binding induces a conformational change, which makes the estrone sulfate
      binding site accessible. Binding of non-hydrolyzable ATP analogues to MRP1
      decreases the affinity for estrone sulfate. However, GSH (or S-mGSH) is still
      required for estrone sulfate binding, and the affinity for GSH is unchanged.
      Estrone sulfate affinity remains low following hydrolysis of ATP. The affinity
      for GSH also appears to decrease in the post-hydrolytic state. Our results
      indicate ATP binding is sufficient for reconfiguration of the estrone sulfate
      binding site to lower affinity and argue for the presence of a modulatory GSH
      binding site not associated with transport of this tripeptide. A model for the
      mechanism of GSH-stimulated estrone sulfate transport is proposed.

PMID- 16565075
TI  - Cystatin M/E is a high affinity inhibitor of cathepsin V and cathepsin L by a
      reactive site that is distinct from the legumain-binding site. A novel clue for
      the role of cystatin M/E in epidermal cornification.
AB  - Cystatin M/E is a high affinity inhibitor of the asparaginyl endopeptidase
      legumain, and we have previously reported that both proteins are likely to be
      involved in the regulation of stratum corneum formation in skin. Although
      cystatin M/E contains a predicted binding site for papain-like cysteine
      proteases, no high affinity binding for any member of this family has been
      demonstrated so far. We report that human cathepsin V (CTSV) and human cathepsin
      L (CTSL) are strongly inhibited by human cystatin M/E. Kinetic studies show that
      Ki values of cystatin M/E for the interaction with CTSV and CTSL are 0.47 and
      1.78 nM, respectively. On the basis of the analogous sites in cystatin C, we used
      site-directed mutagenesis to identify the binding sites of these proteases in
      cystatin M/E. We found that the W135A mutant was rendered inactive against CTSV
      and CTSL but retained legumain-inhibiting activity. Conversely, the N64A mutant
      lost legumain-inhibiting activity but remained active against the papain-like
      cysteine proteases. We conclude that legumain and papain-like cysteine proteases
      are inhibited by two distinct non-overlapping sites. Using immunohistochemistry
      on normal human skin, we found that cystatin M/E co-localizes with CTSV and CTSL.
      In addition, we show that CTSL is the elusive enzyme that processes and activates
      epidermal transglutaminase 3. The identification of CTSV and CTSL as novel
      targets for cystatin M/E, their (co)-expression in the stratum granulosum of
      human skin, and the activity of CTSL toward transglutaminase 3 strongly imply an
      important role for these enzymes in the differentiation process of human
      epidermis.

PMID- 16565076
TI  - New insights into BS69 functions.
AB  - The BS69 protein has been commonly described as a co-repressor associated with
      various transcription factors. However, this hypothesis relied predominantly on
      overexpression of tagged proteins due to the lack of a reliable BS69 antibody. We
      present for the first time a complete sequence of BS69 and valuable tools to
      characterize the endogenous protein. We show that the full-length BS69 protein,
      as well as minor alternatively spliced isoforms, is ubiquitously expressed,
      nuclear, and associates with chromatin and mitotic chromosomes. Accordingly, BS69
      interacts with a set of chromatin remodeling factors, including ATP-dependent
      helicases, histone deacetylases, and histone methyltransferases, as well as the
      E2F6 transcription factor. These data strengthen a role for BS69 in gene
      repression and link BS69 to chromatin remodeling.

PMID- 16565077
TI  - Induction of adaptive response and enhancement of PC12 cell tolerance by 7
      hydroxycholesterol and 15-deoxy-delta(12,14)-prostaglandin J2 through up
      regulation of cellular glutathione via different mechanisms.
AB  - Increasing evidence suggests an adaptive response induced by reactive oxygen
      species and other physiologically existing oxidative stimuli. We have recently
      reported that a variety of lipid peroxidation products at sublethal
      concentrations could induce adaptive response and enhance PC12 cell tolerance,
      although the detailed underlying molecular mechanisms have not been clearly
      clarified. In the present study, we found that both 7-hydroxycholesterol (7-OHCh)
      and 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) at sublethal concentrations
      significantly increased the cellular GSH as well as the enzyme activity of
      glutamate-cysteine ligase (GCL), the rate-limiting enzyme of GSH synthesis.
      Depletion of cellular GSH by buthionine sulfoximine completely abolished the
      adaptive response. Interestingly, treatment with 15d-PGJ2 significantly increased
      the gene expression of both subunits of GCL in an NF-E2-related factor 2 (Nrf2)
      dependent manner, whereas neither 7-OHCh induced any considerable changes on the
      GCL gene expression nor did the Nrf2-small interfering RNA treatment exert any
      appreciable effects on the GSH elevation and subsequent adaptive response induced
      by 7-OHCh. These results demonstrate that the adaptive response induced by both 7
      OHCh and 15d-PGJ2 is mediated similarly through the up-regulation of GSH but via
      different mechanisms.

PMID- 16565079
TI  - Metalloprotease inhibitors GM6001 and TAPI-0 inhibit the obligate intracellular
      human pathogen Chlamydia trachomatis by targeting peptide deformylase of the
      bacterium.
AB  - Chlamydia trachomatis is an obligate intracellular bacterium responsible for a
      number of human diseases. The mechanism underlying the intracellular parasitology
      of Chlamydiae remains poorly understood. In searching for host factors required
      for chlamydial infection, we discovered that C. trachomatis growth was
      effectively inhibited with GM6001 and TAPI-0, two compounds known as specific
      inhibitors of matrix metalloproteases. The inhibition was independent of
      chlamydial entry of the cell, suggesting that the loss of extracellular
      metalloprotease activities of the host cell is unlikely to be the mechanism for
      the growth suppression. Nucleotide sequences of candidate metalloprotease genes
      remained unchanged in a chlamydial variant designated GR10, which had been
      selected for resistance to the inhibitors. Nevertheless, GR10 displayed a single
      base mutation in the presumable promoter region of the gene for peptide
      deformylase (PDF), a metal-dependent enzyme that removes the N-formyl group from
      newly synthesized bacterial proteins. The mutation correlated with an increased
      PDF expression level and resistance to actinonin, a known PDF inhibitor with
      antibacterial activity, as compared with the parental strain. Recombinant
      chlamydial PDF was covalently labeled with a hydroxamate-based molecular probe
      designated AspR1, which was developed for the detection of metalloproteases. The
      AspR1 labeling of the chlamydial PDF became significantly less efficient in the
      presence of excessive amounts of GM6001 and TAPI-0. Finally, the PDF enzyme
      activity was efficiently inhibited with GM6001 and TAPI-0. Taken together, our
      results suggest that the metalloprotease inhibitors suppress chlamydial growth by
      targeting the bacterial PDF. These findings have important biochemical and
      medical implications.

PMID- 16565078
TI  - Metabolite of SIR2 reaction modulates TRPM2 ion channel.
AB  - The transient receptor potential melastatin-related channel 2 (TRPM2) is a
      nonselective cation channel, whose prolonged activation by oxidative and
      nitrative agents leads to cell death. Here, we show that the drug puromycin
      selectively targets TRPM2-expressing cells, leading to cell death. Our data
      suggest that the silent information regulator 2 (Sir2 or sirtuin) family of
      enzymes mediates this susceptibility to cell death. Sirtuins are protein
      deacetylases that regulate gene expression, apoptosis, metabolism, and aging.
      These NAD+-dependent enzymes catalyze a reaction in which the acetyl group from
      substrate is transferred to the ADP-ribose portion of NAD+ to form deacetylated
      product, nicotinamide, and the metabolite OAADPr, whose functions remain elusive.
      Using cell-based assays and RNA interference, we show that puromycin-induced cell
      death is greatly diminished by nicotinamide (a potent sirtuin inhibitor), and by
      decreased expression of sirtuins SIRT2 and SIRT3. Furthermore, we demonstrate
      using channel current recordings and binding assays that OAADPr directly binds to
      the cytoplasmic domain of TRPM2 and activates the TRPM2 channel. ADP-ribose binds
      TRPM2 with similarly affinity, whereas NAD+ displays almost negligible binding.
      These studies provide the first evidence for the potential role of sirtuin
      generated OAADPr in TRPM2 channel gating.

PMID- 16565080
TI  - Staphylococcus aureus operates protein-tyrosine phosphorylation through a
      specific mechanism.
AB  - Protein phosphorylation on tyrosine has been originally characterized in animal
      systems and has been shown to be involved in several fundamental processes
      including signal transduction, growth control, and malignancy. It has been later
      demonstrated to occur also in a number of bacteria, and recent data suggest that
      it may participate in the control of bacterial pathogenicity. In this work, we
      provide evidence that the gram-positive human pathogen Staphylococcus aureus
      harbors a protein-tyrosine kinase activity. This activity is borne by a protein,
      termed Cap5B2, whose phosphorylating capacity is expressed only in the presence
      of a stimulatory protein, either Cap5A1 or Cap5A2, that enhances its affinity for
      the phosphoryl donor ATP. In fact, the last 27/29 amino acids of the C-terminal
      domain of either polypeptide are sufficient for stimulating Cap5B2 activity. The
      stimulation of Cap5B2 by Cap5A1 involves essentially three amino acid residues in
      a helix of Cap5A1 (Asp202, Glu203, and Asp205) and three residues in a helix
      (helix 7) of Cap5B2 (Glu190, Lys192, and Lys193), thus suggesting helix-helix
      interaction between these two proteins. This type of helix-helix interaction
      resembles the interaction required for the activation of MinD ATPase by MinE
      protein in the process of septum-site determination, MinD sharing sequence
      similarity with Cap5B2. Such activation mechanism is described here in a gram
      positive bacterial tyrosine kinase, and differs from the activation mechanism
      previously proposed for gram-negative bacteria. Therefore, it appears that S.
      aureus, and possibly other gram-positive bacteria, utilizes a specific molecular
      mechanism for triggering protein-tyrosine kinase activity.

PMID- 16565081
TI  - Deregulated activation of oncoprotein kinase Tpl2/Cot in HTLV-I-transformed T
      cells.
AB  - Protein kinase Tpl2/Cot is encoded by a protooncogene that is cis-activated by
      retroviral insertion in murine T cell lymphomas. It has remained unclear whether
      this oncoprotein kinase is mutated or post-translationally activated in human
      cancer cells. We have shown here that Tpl2/Cot is constitutively activated in
      human leukemia cell lines transformed by the human T cell leukemia virus type I
      (HTLV-I). The kinase activity of Tpl2/Cot is normally suppressed through its
      physical interaction with an inhibitor, the NF-kappaB1 precursor protein p105.
      Interestingly, a large pool of Tpl2/Cot is liberated from p105 and exhibits
      constitutive kinase activity in HTLV-I-transformed T cells. In contrast to its
      labile property in normal cells, the pathologically activated Tpl2/Cot is
      remarkably stable. Further, whereas the physiological activation of Tpl2/Cot
      involves its long isoform, the HTLV-activated Tpl2/Cot is predominantly the short
      isoform. We have also shown that the HTLV-I-encoded Tax protein is able to
      activate Tpl2/Cot in transfected cells. Finally, Tpl2/Cot participates in the
      activation of NF-kappaB by Tax. These findings indicate that deregulated
      activation of Tpl2/Cot may occur in human cancer cells.

PMID- 16565082
TI  - Crystal structure of heparinase II from Pedobacter heparinus and its complex with
      a disaccharide product.
AB  - Heparinase II depolymerizes heparin and heparan sulfate glycosaminoglycans,
      yielding unsaturated oligosaccharide products through an elimination degradation
      mechanism. This enzyme cleaves the oligosaccharide chain on the nonreducing end
      of either glucuronic or iduronic acid, sharing this characteristic with a
      chondroitin ABC lyase. We have determined the first structure of a heparin
      degrading lyase, that of heparinase II from Pedobacter heparinus (formerly
      Flavobacterium heparinum), in a ligand-free state at 2.15 A resolution and in
      complex with a disaccharide product of heparin degradation at 2.30 A resolution.
      The protein is composed of three domains: an N-terminal alpha-helical domain, a
      central two-layered beta-sheet domain, and a C-terminal domain forming a two
      layered beta-sheet. Heparinase II shows overall structural similarities to the
      polysaccharide lyase family 8 (PL8) enzymes chondroitin AC lyase and hyaluronate
      lyase. In contrast to PL8 enzymes, however, heparinase II forms stable dimers,
      with the two active sites formed independently within each monomer. The structure
      of the N-terminal domain of heparinase II is also similar to that of alginate
      lyases from the PL5 family. A Zn2+ ion is bound within the central domain and
      plays an essential structural role in the stabilization of a loop forming one
      wall of the substrate-binding site. The disaccharide binds in a long, deep canyon
      formed at the top of the N-terminal domain and by loops extending from the
      central domain. Based on structural comparison with the lyases from the PL5 and
      PL8 families having bound substrates or products, the disaccharide found in
      heparinase II occupies the "+1" and "+2" subsites. The structure of the enzyme
      product complex, combined with data from previously characterized mutations,
      allows us to propose a putative chemical mechanism of heparin and heparan-sulfate
      degradation.

PMID- 16565083
TI  - Pharmacological chaperone activity of SR49059 to functionally recover misfolded
      mutations of the vasopressin V1a receptor.
AB  - Pharmacological chaperones represent a new class of ligand with the potential to
      facilitate the delivery of misfolded, but still active, G-protein-coupled
      receptors to the cell surface. Using transfected HEK 293T cells, treatment with a
      nonpeptide antagonist, SR49059, dramatically increased ( approximately 60-fold)
      the surface expression of a misfolded, nonfunctional and intracellularly
      localized vasopressin V(1a) receptor (V(1a)R) mutant (D148A). This rescue of
      surface expression (111 +/- 7%) was almost identical to wild type assessed by
      confocal microscopy and quantitative enzyme-linked immunosorbent assay-based
      techniques. Recovery was not specific to D148A, since other surface-impaired
      mutations, D148N and D148E, and wild type were also increased following SR49059
      exposure. However, surface delivery was specific to SR49059, since V(1a)R
      selective peptide ligands or unrelated ligands were unable to mimic this action,
      suggesting that SR49059 acts intracellularly. SR49059-mediated surface rescue was
      time-, mutant-, and concentration-dependent but not directly related to its
      binding affinity. Maximal recovery was achieved following 12 h of treatment and
      did not involve de novo receptor synthesis or a consequence of preventing
      endogenous constitutive activity and/or internalization. Once at the surface, all
      mutants displayed enhanced signaling ability, and D148A was able to undergo
      agonist-mediated internalization. SR49059 was not effectively removed from the
      receptor, since signaling (EC(50)) of both wild type and D148A was reduced
      approximately 40-fold. This is the first report of a pharmacological chaperone
      ligand to act on misfolded mutant V(1a) Rs. This work provides an excellent model
      to understand the mechanistic action of an important new class of drug that may
      have potential in the treatment of diseases caused by inherited mutations.

PMID- 16565084
TI  - Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent
      dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathways.
AB  - Studies of gene regulation by oxygen have revealed novel signal pathways that
      regulate the hypoxia-inducible factor (HIF) transcriptional system through post
      translational hydroxylation of specific prolyl and asparaginyl residues in HIF
      alpha subunits. These oxygen-sensitive modifications are catalyzed by members of
      the 2-oxoglutarate (2-OG) dioxygenase family (PHD1, PHD2, PHD3, and FIH-1),
      raising an important question regarding the extent of involvement of these and
      other enzymes of the same family in directing the global changes in gene
      expression that are induced by hypoxia. To address this, we compared patterns of
      gene expression induced by hypoxia and by a nonspecific 2-OG-dependent
      dioxygenase inhibitor, dimethyloxalylglycine (DMOG), among a set of 22,000
      transcripts, by microarray analysis of MCF7 cells. By using short interfering RNA
      based suppression of HIF-alpha subunits, we also compared responses that were
      dependent on, or independent of, the HIF system. Results revealed striking
      concordance between patterns of gene expression induced by hypoxia and by DMOG,
      indicating the central involvement of 2-OG-dependent dioxygenases in oxygen
      regulated gene expression. Many of these responses were suppressed by short
      interfering RNAs directed against HIF-1alpha and HIF-2alpha, with HIF-1alpha
      suppression manifesting substantially greater effects than HIF-2alpha
      suppression, supporting the importance of HIF pathways. Nevertheless, the
      definition of genes regulated by both hypoxia and DMOG, but not HIF,
      distinguished other pathways most likely involving the action of 2-OG-dependent
      dioxygenases on non-HIF substrates.

PMID- 16565085
TI  - Molecular mechanism of the reduction of cysteine sulfinic acid of peroxiredoxin
      to cysteine by mammalian sulfiredoxin.
AB  - Among many proteins with cysteine sulfinic acid (Cys-SO2H) residues, the sulfinic
      forms of certain peroxiredoxins (Prxs) are selectively reduced by sulfiredoxin
      (Srx) in the presence of ATP. All Srx enzymes contain a conserved cysteine
      residue. To elucidate the mechanism of the Srx-catalyzed reaction, we generated
      various mutants of Srx and examined their interaction with PrxI, their ATPase
      activity, and their ability to reduce sulfinic PrxI. Our results suggest that
      three surface-exposed amino acid residues, corresponding to Arg50, Asp57, and
      Asp79 of rat Srx, are critical for substrate recognition. The presence of the
      sulfinic form (but not the reduced form) of PrxI induces the conserved cysteine
      of Srx to take the gamma-phosphate of ATP and then immediately transfers the
      phosphate to the sulfinic moiety of PrxI to generate a sulfinic acid phosphoryl
      ester (Prx-Cys-S(=O)OPO3(2-)). This ester is reductively cleaved by a thiol
      molecule (RSH) such as GSH, thioredoxin, and dithiothreitol to produce a
      disulfide-S-monoxide (Prx-Cys-S(=O)-S-R). The disulfide-S-monoxide is further
      reduced through the oxidation of three thiol equivalents to complete the
      catalytic cycle and regenerate Prx-Cys-SH.

PMID- 16565086
TI  - Only one protomer is active in the dimer of SARS 3C-like proteinase.
AB  - The severe acute respiratory syndrome coronavirus 3C-like protease has been
      proposed to be a key target for structurally based drug design against SARS. The
      enzyme exists as a mixture of dimer and monomer, and only the dimer was
      considered to be active. In this report, we have investigated, using molecular
      dynamics simulation and mutational studies, the problems as to why only the dimer
      is active and whether both of the two protomers in the dimer are active. The
      molecular dynamics simulations show that the monomers are always inactive, that
      the two protomers in the dimer are asymmetric, and that only one protomer is
      active at a time. The enzyme activity of the hybrid severe acute respiratory
      syndrome coronavirus 3C-like protease of the wild-type protein and the inactive
      mutant proves that the dimerization is important for enzyme activity and only one
      active protomer in the dimer is enough for the catalysis. Our simulations also
      show that the right conformation for catalysis in one protomer can be induced
      upon dimer formation. These results suggest that the enzyme may follow the
      association, activation, catalysis, and dissociation mechanism for activity
      control.

PMID- 16565087
TI  - RhoA/ROCK signaling regulates chondrogenesis in a context-dependent manner.
AB  - The development of the cartilage template that precedes endochondral bone
      formation requires the condensation of mesenchymal cells and their subsequent
      differentiation to the chondrocytic lineage. We have previously shown that
      inhibition of the RhoA/ROCK signaling pathway or actin dynamics enhances Sox9
      mRNA expression, increases glycosaminoglycan production, and transforms cell
      shape to a spherical, chondrocyte-like morphology. However, we demonstrate here
      that in three-dimensional micromass cultures of mesenchymal cells, increased
      expression of Sox9 in response to these manipulations is not sufficient to induce
      the expression of established Sox9 target genes. This is illustrated by a
      decrease in the transcript levels of collagen II and aggrecan as well as reduced
      activity of a Sox9-responsive reporter gene in response to ROCK inhibition and
      cytochalasin D. We also demonstrate a decrease in mRNA levels of the
      transcriptional co-activators L-Sox5 and Sox6 upon ROCK inhibition and
      cytochalasin D. The decrease in Sox9 activity is likely partially due to reduced
      L-Sox5 and Sox6 levels but also to a delay in Sox9 phosphorylation following ROCK
      inhibition. In contrast, inhibition of the RhoA/ROCK pathway and cytochalasin D
      treatment in monolayer culture results in the enhancement of a number of markers
      of chondrogenesis such as Sox9 activity and collagen II and aggrecan transcripts
      levels. These data demonstrate that the effects of RhoA/ROCK signaling and actin
      polymerization inhibitors on chondrogenic gene expression are dependent on the
      cellular context.

PMID- 16565088
TI  - Interaction of the B cell-specific transcriptional coactivator OCA-B and galectin
      1 and a possible role in regulating BCR-mediated B cell proliferation.
AB  - OCA-B is a B cell-specific transcriptional coactivator for OCT factors during the
      activation of immunoglobulin genes. In addition, OCA-B is crucial for B cell
      activation and germinal center formation. However, the molecular mechanisms for
      OCA-B function in these processes are not clear. Our previous studies documented
      two OCA-B isoforms and suggested a novel mechanism for the function of the
      myristoylated, membrane-bound form of OCA-B/p35 as a signaling molecule. Here, we
      report the identification of galectin-1, and related galectins, as a novel OCA-B
      interacting protein. The interaction of OCA-B and galectin-1 can be detected both
      in vivo and in vitro. The galectin-1 binding domain in OCA-B has been localized
      to the N terminus of OCA-B. In B cells lacking OCA-B expression, increased
      galectin-1 expression, secretion, and cell surface association are observed.
      Consistent with these observations, and a reported inhibitory interaction of
      galectin-1 with CD45, the phosphatase activity of CD45 is reduced modestly, but
      significantly, in OCA-B-deficient B cells. Finally, galectin-1 is shown to
      negatively regulate B cell proliferation and tyrosine phosphorylation upon BCR
      stimulation. Together, these results raise the possibility that OCA-B may
      regulate BCR signaling through an association with galectin-1.

PMID- 16565090
TI  - Mediator is a transducer of Wnt/beta-catenin signaling.
AB  - Signal transduction within the canonical Wnt/beta-catenin pathway drives
      development and carcinogenesis through programmed or unprogrammed changes in gene
      transcription. Although the upstream events linked to signal-induced activation
      of beta-catenin in the cytoplasm have been deciphered in considerable detail,
      much less is known regarding the mechanism by which beta-catenin stimulates
      target gene transcription in the nucleus. Here, we show that beta-catenin
      physically and functionally targets the MED12 subunit in Mediator to activate
      transcription. The beta-catenin transactivation domain bound directly to isolated
      MED12 and intact Mediator both in vitro and in vivo, and Mediator was recruited
      to Wnt-responsive genes in a beta-catenin-dependent manner. Disruption of the
      beta-catenin/MED12 interaction through dominant-negative interference- or RNA
      interference-mediated MED12 suppression inhibited beta-catenin transactivation in
      response to Wnt signaling. This study thus identifies the MED12 interface within
      Mediator as a new component and a potential therapeutic target in the Wnt/beta
      catenin pathway.

PMID- 16565089
TI  - Hyaluronan-CD44 interaction with leukemia-associated RhoGEF and epidermal growth
      factor receptor promotes Rho/Ras co-activation, phospholipase C epsilon-Ca2+
      signaling, and cytoskeleton modification in head and neck squamous cell carcinoma
      cells.
AB  - In this study we have examined the interaction of CD44 (a major hyaluronan (HA)
      receptor) with a RhoA-specific guanine nucleotide exchange factor (leukemia
      associated RhoGEF (LARG)) in human head and neck squamous carcinoma cells (HNSCC
      HSC-3 cell line). Immunoprecipitation and immunoblot analyses indicate that CD44
      and the LARG protein are expressed in HSC-3 cells and that these two proteins are
      physically associated as a complex. HA-CD44 binding induces LARG-specific RhoA
      signaling and phospholipase C epsilon (PLC epsilon) activity. In particular, the
      activation of RhoA-PLC epsilon by HA stimulates inositol 1,4,5-triphosphate
      production, intracellular Ca2+ mobilization, and the up-regulation of
      Ca2+/calmodulin-dependent kinase II (CaMKII), leading to phosphorylation of the
      cytoskeletal protein, filamin. The phosphorylation of filamin reduces its
      interaction with filamentous actin, promoting tumor cell migration. The CD44-LARG
      complex also interacts with the EGF receptor (EGFR). Most importantly, the
      binding of HA to the CD44-LARG-EGFR complex activates the EGFR receptor kinase,
      which in turn promotes Ras-mediated stimulation of a downstream kinase cascade
      including the Raf-1 and ERK pathways leading to HNSCC cell growth. Using a
      recombinant fragment of LARG (the LARG-PDZ domain) and a binding assay, we have
      determined that the LARG-PDZ domain serves as a direct linker between CD44 and
      EGFR. Transfection of the HSC-3 cells with LARG-PDZcDNA significantly reduces
      LARG association with CD44 and EGFR. Overexpression of the LARG-PDZ domain also
      functions as a dominant-negative mutant (similar to the PLC/Ca2+-calmodulin
      dependent kinase II (CaMKII) and EGFR/MAPK inhibitor effects) to block HA/CD44
      mediated signaling events (e.g. EGFR kinase activation, Ras/RhoA co-activation,
      Raf-ERK signaling, PLC epsilon-mediated inositol 1,4,5-triphosphate production,
      intracellular Ca2+ mobilization, CaMKII activity, filamin phosphorylation, and
      filamin-actin binding) and to abrogate tumor cell growth/migration. Taken
      together, our findings suggest that CD44 interaction with LARG and EGFR plays a
      pivotal role in Rho/Ras co-activation, PLC epsilon-Ca2+ signaling, and Raf/ERK up
      regulation required for CaMKII-mediated cytoskeleton function and in head and
      neck squamous cell carcinoma progression.

PMID- 16565091
TI  - Identification of an osteocalcin isoform in fish with a large acidic prodomain.
AB  - Osteocalcin is a small, secreted bone protein whose gene consists of four exons.
      In the course of analyzing the structure of fish osteocalcin genes, we recently
      found that the spotted green pufferfish has two possible exon 2 structures, one
      of 15 bp and the other of 324 bp. Subsequent analysis of the pufferfish cDNA
      showed that only the transcript with a large exon 2 exists. Exon 2 codes for the
      osteocalcin propeptide, and exon 2 of pufferfish osteocalcin is approximately 3.4
      fold larger than exon 2 previously found in other vertebrate species. We have
      termed this new pufferfish osteocalcin isoform OC2. Additional studies showed
      that the OC2 isoform is restricted to a unique fish taxonomic group, the
      Osteichthyes; OC2 is the only osteocalcin isoform found so far in six
      Osteichthyes species, whereas both OC1 and OC2 isoforms coexist in zebrafish and
      rainbow trout. The larger size of the OC2 propeptide is due to an acidic region
      that is likely to be highly phosphorylated and has no counterpart in the OC1
      propeptide. We propose 1) that OC1 and OC2 are encoded by distinct genes that
      originated from a duplication event that probably occurred in the teleost fish
      lineage soon after divergence from tetrapods and 2) that the novel OC2 propeptide
      could be, if secreted, a phosphoprotein that participates in the regulation of
      biomineralization through its large acidic and phosphorylated propeptide.

PMID- 16565092
TI  - HCELL is the major E- and L-selectin ligand expressed on LS174T colon carcinoma
      cells.
AB  - Engagement of vascular E-selectin and leukocyte L-selectin with relevant counter
      receptors expressed on tumor cells contributes to the hematogenous spread of
      colon carcinoma. We recently demonstrated that the LS174T colon carcinoma cell
      line expresses the CD44 glycoform known as hematopoietic cell E-/L-selectin
      ligand (HCELL), which functions as a high affinity E- and L-selectin ligand on
      these cells. To define the contribution of HCELL to selectin-mediated adhesion on
      intact tumor cells, we measured the binding of LS174T cells transduced with CD44
      short interfering RNA (siRNA) or with vector alone to 6-h interleukin-1beta
      stimulated human umbilical vein endothelial cells (HUVEC) and to human peripheral
      blood mononuclear cells (PBMC) under physiological flow conditions. LS174T cell
      attachment to HUVEC was entirely E-selectin-dependent, and PBMC tethering to
      tumor cell monolayers was completely L-selectin-dependent. At physiological shear
      stress, CD44 siRNA transduction led to an approximately 50% decrease in the
      number of LS174T cells binding to stimulated HUVEC relative to vector alone
      transduced cells. CD44 siRNA-transduced cells also rolled significantly faster
      than vector-transduced cells on HUVEC, indicating prominent HCELL participation
      in stabilizing tumor cell-endothelial adhesive interactions against fluid shear.
      Furthermore, HCELL was identified as the principal L-selectin ligand on LS174T
      cells, as PBMC binding to CD44 siRNA-transduced tumor cells was reduced
      approximately 80% relative to vector-transduced cells. These data indicate that
      expression of HCELL confers robust and predominant tumor cell binding to E- and L
      selectin, highlighting a central role for HCELL in promoting shear-resistant
      adhesive interactions essential for hematogenous cancer dissemination.

PMID- 16565093
TI  - Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and
      cancer: systematic review.
AB  - OBJECTIVE: To review systematically the evidence for an effect of long chain and
      shorter chain omega 3 fatty acids on total mortality, cardiovascular events, and
      cancer. DATA SOURCES: Electronic databases searched to February 2002; authors
      contacted and bibliographies of randomised controlled trials (RCTs) checked to
      locate studies. REVIEW METHODS: Review of RCTs of omega 3 intake for (3) 6 months
      in adults (with or without risk factors for cardiovascular disease) with data on
      a relevant outcome. Cohort studies that estimated omega 3 intake and related this
      to clinical outcome during at least 6 months were also included. Application of
      inclusion criteria, data extraction, and quality assessments were performed
      independently in duplicate. RESULTS: Of 15,159 titles and abstracts assessed, 48
      RCTs (36,913 participants) and 41 cohort studies were analysed. The trial results
      were inconsistent. The pooled estimate showed no strong evidence of reduced risk
      of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or
      combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking
      additional omega 3 fats. The few studies at low risk of bias were more
      consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70
      to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the
      subgroup of studies of long chain omega 3 fats were analysed separately, total
      mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79
      to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested
      increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to
      1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could
      not be excluded. CONCLUSION: Long chain and shorter chain omega 3 fats do not
      have a clear effect on total mortality, combined cardiovascular events, or
      cancer.

PMID- 16565094
TI  - Oily fish and omega 3 fat supplements.

PMID- 16565096
TI  - Accuracy of magnetic resonance imaging for the diagnosis of multiple sclerosis:
      systematic review.
AB  - OBJECTIVE: To determine the accuracy of magnetic resonance imaging criteria for
      the early diagnosis of multiple sclerosis in patients with suspected disease.
      DESIGN: Systematic review. DATA SOURCES: 12 electronic databases, citation
      searches, and reference lists of included studies. Review methods Studies on
      accuracy of diagnosis that compared magnetic resonance imaging, or diagnostic
      criteria incorporating such imaging, to a reference standard for the diagnosis of
      multiple sclerosis. RESULTS: 29 studies (18 cohort studies, 11 other designs)
      were included. On average, studies of other designs (mainly diagnostic case
      control studies) produced higher estimated diagnostic odds ratios than did cohort
      studies. Among 15 studies of higher methodological quality (cohort design,
      clinical follow-up as reference standard), those with longer follow-up produced
      higher estimates of specificity and lower estimates of sensitivity. Only two such
      studies followed patients for more than 10 years. Even in the presence of many
      lesions (> 10 or > 8), magnetic resonance imaging could not accurately rule
      multiple sclerosis in (likelihood ratio of a positive test result 3.0 and 2.0,
      respectively). Similarly, the absence of lesions was of limited utility in ruling
      out a diagnosis of multiple sclerosis (likelihood ratio of a negative test result
      0.1 and 0.5). CONCLUSIONS: Many evaluations of the accuracy of magnetic resonance
      imaging for the early detection of multiple sclerosis have produced inflated
      estimates of test performance owing to methodological weaknesses. Use of magnetic
      resonance imaging to confirm multiple sclerosis on the basis of a single attack
      of neurological dysfunction may lead to over-diagnosis and over-treatment.

PMID- 16565097
TI  - Evaluating new screening tests for breast cancer.

PMID- 16565098
TI  - Acupressure for low back pain.

PMID- 16565099
TI  - Improving the management of dementia.

PMID- 16565100
TI  - Alcohol misuse and ethnicity.

PMID- 16565101
TI  - Severe adverse reactions prompt call for trial design changes.

PMID- 16565102
TI  - Researchers funded by NIH are failing to make data available.

PMID- 16565105
TI  - Judge rules that baby boy should not be allowed to die.

PMID- 16565106
TI  - European group targets overuse of antibiotics.

PMID- 16565111
TI  - US cigarette consumption falls to lowest point since 1951.

PMID- 16565114
TI  - Israelis won't get cover for transplantations unless they can show organ is
      legal.

PMID- 16565115
TI  - Civil rights group urges Czech government to act on report on sterilisation of
      Gypsies.

PMID- 16565117
TI  - Extending life brings conceptual as well as technological challenges.

PMID- 16565120
TI  - Tuberculosis guidance aims to improve case detection and reduce drug resistance.

PMID- 16565122
TI  - Doctors will test whether Mozart can reduce stress in babies.

PMID- 16565124
TI  - Effectiveness of educational interventions in improving detection and management
      of dementia in primary care: cluster randomised controlled study.
AB  - OBJECTIVE: To test the effectiveness of educational interventions in improving
      detection rates and management of dementia in primary care. DESIGN: Unblinded,
      cluster randomised, before and after controlled study. SETTING: General practices
      in the United Kingdom (central Scotland and London) between 1999 and 2002.
      INTERVENTIONS: Three educational interventions: an electronic tutorial carried on
      a CD Rom; decision support software built into the electronic medical record; and
      practice based workshops. PARTICIPANTS: 36 practices participated in the study.
      Eight practices were randomly assigned to the electronic tutorial; eight to
      decision support software; 10 to practice based workshops; and 10 to control.
      Electronic and manual searches yielded 450 valid and usable medical records. MAIN
      OUTCOME MEASURES: Rates of detection of dementia and the extent to which medical
      records showed evidence of improved concordance with guidelines regarding
      diagnosis and management. RESULTS: Decision support software (P = 0.01) and
      practice based workshops (P = 0.01) both significantly improved rates of
      detection compared with control. There were no significant differences by
      intervention in the measures of concordance with guidelines. CONCLUSIONS:
      Decision support systems and practice based workshops are effective educational
      approaches in improving detection rates in dementia.

PMID- 16565125
TI  - Disorders of sodium balance.

PMID- 16565126
TI  - Accidental hypothermia.

PMID- 16565127
TI  - Reconstructive surgery.

PMID- 16565129
TI  - Should all children be immunised against hepatitis A?

PMID- 16565130
TI  - Contracting out health services in fragile states.

PMID- 16565131
TI  - No clear evidence from countries that have enforced the wearing of helmets.

PMID- 16565133
TI  - Arguments against helmet legislation are flawed.

PMID- 16565134
TI  - Ramifications of screening for breast cancer: definition of overdiagnosis is
      confusing in follow-up of Malmo trial.

PMID- 16565135
TI  - Ramifications of screening for breast cancer: overdiagnosis in the Malmo trial
      was considerably underestimated.

PMID- 16565136
TI  - Ramifications of screening for breast cancer: 1 in 4 cancers detected by
      mammography are pseudocancers.

PMID- 16565137
TI  - Prophylactic heparin in palliative care: a cautious welcome...

PMID- 16565138
TI  - Ramifications of screening for breast cancer: more debate and better information
      still needed.

PMID- 16565139
TI  - Ramifications of screening for breast cancer: consent for screening.

PMID- 16565140
TI  - Effectiveness of hip protectors: it's more the effectiveness of compliance
      strategies.

PMID- 16565141
TI  - Effectiveness of hip protectors: wider picture is important.

PMID- 16565142
TI  - Prophylactic heparin in palliative care: ...to a challenging idea.

PMID- 16565144
TI  - Ethics committees: we all need research ethics committees.

PMID- 16565143
TI  - Approval of inhaled insulin in Europe and United States.

PMID- 16565145
TI  - Ethics committees: current research ethics forms are an over-reaction that will
      stifle research.

PMID- 16565148
TI  - A Laplace mixture model for identification of differential expression in
      microarray experiments.
AB  - Microarrays have become an important tool for studying the molecular basis of
      complex disease traits and fundamental biological processes. A common purpose of
      microarray experiments is the detection of genes that are differentially
      expressed under two conditions, such as treatment versus control or wild type
      versus knockout. We introduce a Laplace mixture model as a long-tailed
      alternative to the normal distribution when identifying differentially expressed
      genes in microarray experiments, and provide an extension to asymmetric over- or
      underexpression. This model permits greater flexibility than models in current
      use as it has the potential, at least with sufficient data, to accommodate both
      whole genome and restricted coverage arrays. We also propose likelihood
      approaches to hyperparameter estimation which are equally applicable in the
      Normal mixture case. The Laplace model appears to give some improvement in fit to
      data, though simulation studies show that our method performs similarly to
      several other statistical approaches to the problem of identification of
      differential expression.

PMID- 16565147
TI  - A simple approach for protein structure discrimination based on the network
      pattern of conserved hydrophobic residues.
AB  - Evolutionarily conserved hydrophobic residues at the core of protein structures
      are generally assumed to play a structural role in protein folding and stability.
      Recent studies have implicated that their importance to protein structures is
      uneven, with a few of them being crucial and the rest of them being secondary. In
      this work, we explored the possibility of employing this feature of native
      structures for discriminating non-native structures from native ones. First, we
      developed a network tool to quantitatively measure the structural contributions
      of individual amino acid residues. We systematically applied this method to
      diverse fold-type sets of native proteins. It was confirmed that this method
      could grasp the essential structural features of native proteins. Next, we
      applied it to a number of decoy sets of proteins. The results indicate that such
      an approach indeed identified non-native structures in most test cases. This
      finding should be of help for the investigation of the fundamental problem of
      protein structure prediction.

PMID- 16565146
TI  - Statistical analysis and prediction of functional residues effective for GPCR-G
      protein coupling selectivity.
AB  - One of the important issues in G-protein-coupled receptor (GPCR) functional
      analysis is the mechanism of GPCR-G-protein coupling selectivity. G-proteins are
      classified into Gi/o, Gq/11 and Gs families. Although several experimental and
      computational analyses have been attempted, the mechanism remains unknown to this
      day. In this study, we have analyzed the multiple sequence alignments of GPCRs of
      known coupling selectivities by mapping onto the tertiary structure of rhodopsin.
      We identified several functional residue sites in GPCRs related to coupling
      selectivity, which are located mainly at the intracellular loops, and found that
      the occurrence of positively/negatively charged amino acids of the characteristic
      residues varies depending on the G-protein coupling selectivity. Especially, the
      occurrence of positively charged amino acids in receptors coupling to Gs family
      is less than that in receptors coupling to Gi/o and Gq/11 families. It is
      interesting that some characteristic residues are located near the extracellular
      terminus of transmembrane helices, which is far from the GPCR/G-protein binding
      interface. In most of the receptors coupling to Gs family, the occurrence of
      proline on the position corresponding to the 170th residue on rhodopsin is rare.
      These findings are vital to improving our understanding of the mechanism of G
      protein coupling selectivity.

PMID- 16565149
TI  - Factors contributing to dwarfing in the mangrove Avicennia marina.
AB  - BACKGROUND AND AIMS: In Richards Bay, South Africa, Avicennia marina frequently
      exhibits a distinct productivity gradient, with tree height decreasing markedly
      from 6-10 m in the fringe zone to <1.5 m in the dwarf zone which is 120 m inland
      at a slightly higher elevation. In this investigation, soil physico-chemical
      conditions between fringe and dwarf A. marina were compared and the constraints
      imposed by any differences on mangrove ecophysiology and productivity determined.
      METHODS: Soil and plant samples were analysed for inorganic ions using
      spectrophotometry. Gas exchange measurements were taken with an infrared gas
      analyser and chlorophyll fluorescence with a fluorometer. Xylem psi was
      determined with a pressure chamber and chlorophyll content with a chlorophyll
      absorbance meter. RESULTS: In the dwarf site, soil salinity, total cations,
      electrical conductivity and soil concentrations of Na(+), K(+), Ca(2+), Mg(2+),
      Zn(2+), Mn(2+) and Cu(2+) were significantly higher than those in the fringe
      zone. Soil water potential and the concentration of soil P, however, were
      significantly lower in the dwarf site. In the leaves, Na(+) was the predominant
      ion and its concentration was 24 % higher in dwarf than fringe mangroves. Leaf
      concentrations of K(+), Ca(2+), Mg(2+), Mn(2+) and P, however, were significantly
      lower in dwarf mangroves. Photosynthetic performance, measured by gas exchange
      and chlorophyll fluorescence, was significantly reduced in the dwarf plants.
      CONCLUSIONS: The results suggest that hydro-edaphic factors contribute to high
      soil salinities, low water potentials, water stress and ion imbalance within
      tissues including P deficiency, which in interaction, contribute to dwarfing in
      Avicennia marina.

PMID- 16565150
TI  - Physiological changes in gentian axillary buds during two-step preculturing with
      sucrose that conferred high levels of tolerance to desiccation and
      cryopreservation.
AB  - BACKGROUND AND AIMS: Induction of dehydration tolerance is a key to achieving
      high survival rates in cryopreservation of plant specimens. It has been reported
      previously that two-step preculturing with sucrose effectively increased
      desiccation tolerance in axillary buds of gentian (Gentiana scabra), which allow
      the buds to survive cryopreservation. This study is aimed at characterizing each
      step of this preculturing and to elucidate physiological changes induced during
      this preculturing. METHODS: In standard two-step preculture, excised gentian
      axillary buds were incubated for 11 d on MS medium with 0.1 m sucrose at 25
      degrees C (first step: mild osmotic stress was given) and the subsequent
      incubation on MS medium with 0.4 m and 0.7 m sucrose for 1 d each (second step).
      The levels of abscisic acid (ABA), proline and soluble sugars in gentian buds
      during the preculture were determined. Effects of various combinations of two
      step preculturing and of exogenous ABA and proline were studied. KEY RESULTS:
      During the first preculture step, there was a transient increase in ABA content
      peaking on day 4, which declined to a background level at the end of the first
      and second step preculturing. Proline level increased steadily during the first
      preculture step and increased further in the second preculture step. Incubating
      buds with medium containing proline, instead of the two-step preculturing, did
      not allow them to survive desiccation. Incubating buds with ABA instead of 0.1 m
      sucrose-preculturing effectively increased desiccation tolerance only when it was
      followed by the second preculture step. Fluridone, an ABA synthesis inhibitor
      included in the two-step preculture medium, reduced desiccation tolerance of the
      buds. The normal first-step preculture increased the levels of soluble sugars 2.4
      fold, especially sucrose and raffinose. Buds treated with the second preculture
      step had greatly increased sucrose levels. CONCLUSIONS: These observations lead
      to the hypothesis that the first preculture step involves ABA-mediated cellular
      changes and the second step induces loading of sucrose in the gentian buds.

PMID- 16565151
TI  - Reducing under-five mortality through Hopital Albert Schweitzer's integrated
      system in Haiti.
AB  - BACKGROUND: The degree to which local health systems contribute to reductions in
      under-five mortality in severely impoverished settings has not been well
      documented. The current study compares the under-five mortality in the Hopital
      Albert Schweitzer (HAS) Primary Health Care Service Area with that for Haiti in
      general. HAS provides an integrated system of community-based primary health care
      services, hospital care and community development. METHODS: A sample of 10% of
      the women of reproductive age in the HAS service area was interviewed, and 2390
      live births and 149 child deaths were documented for the period 1995-99. Under
      five mortality rates were computed and compared with rates for Haiti. In
      addition, available data regarding inputs, processes and outputs for the HAS
      service area and for Haiti were assembled and compared. RESULTS: Under-five
      mortality was 58% less in the HAS service area, and mortality for children 12-59
      months of age was 76% less. These results were achieved with an input of fewer
      physicians and hospital beds per capita than is available for Haiti nationwide,
      but with twice as many graduate nurses and auxiliary nurses per capita than are
      available nationwide, and with three cadres of health workers that do not exist
      nationwide: Physician Extenders, Health Agents and Community Health Volunteers.
      The population coverage of targeted child survival services was generally 1.5-2
      times higher in the HAS service area than in rural Haiti. DISCUSSION: These
      findings support the conclusion that a well-developed system of primary health
      care, with outreach services to the household level, integrated with hospital
      referral care and community development programmes, can make a strong
      contribution to reducing infant and child mortality in severely impoverished
      settings.

PMID- 16565152
TI  - Rehabilitating the health system after conflict in East Timor: a shift from NGO
      to government leadership.
AB  - Efforts to rehabilitate health systems after periods of prolonged conflict have
      often been characterized by poor coordination of external actors - multilateral
      agencies, donors and non-governmental organizations (NGOs). This paper describes
      the process and analyses the roles of the different stakeholders in the
      establishment of a government-led district health system in East Timor, between
      1999 and 2002, after decades of chronic conflict and Indonesian occupation.
      Future East Timorese policy-makers and health professionals began to mobilize in
      May 1999, in preparation for independence. During the emergency phase, from
      September 1999, when violence erupted, to March 2000, NGOs played a major role in
      the provision of relief to the population, coordinated by United Nations
      agencies. An Interim Health Authority, led by local Timorese, was established in
      March and the major donors began to shift funding from NGOs to the newly
      established Ministry of Health. A rapid phasing-out of NGOs, accompanied by a
      sequence of steps to build the capacity of Timorese to manage the new district
      health system, was implemented. Early evidence shows that health service
      utilization continued to grow during and after implementation.

PMID- 16565154
TI  - Knockout mouse models of sperm flagellum anomalies.
AB  - To date, 21 knockout mouse models are known to bear specific anomalies of the
      sperm flagellum structures leading to motility disorders. In addition, genes
      responsible for flagellar defects of two well-known spontaneous mutant mice have
      recently been identified. These models reveal genetic factors, which are required
      for the proper assembly of the axoneme, the annulus, the mitochondrial sheath and
      the fibrous sheath. Many of these genetic factors follow unexpected cellular
      pathways to act on sperm flagellum morphogenesis. These mouse models may bear
      anomalies which are restricted to the spermatozoa or display more complex
      phenotypes that often include neuropathies and/or cilia-related diseases. In
      human, several structural disorders of the sperm flagellum found in brothers or
      consanguineous men probably have a genetic origin, but the genes involved have
      not yet been identified. The mutant mice we present in this review are invaluable
      models, which can be used to identify potential candidate genes for infertile men
      with specific sperm flagellum anomalies.

PMID- 16565153
TI  - Insight into the nature of the CRP-coronary event association using Mendelian
      randomization.
AB  - BACKGROUND: It is unclear wheather the association between C-reactive protein
      (CRP) and incident coronary events is free from bias and confounding. Individuals
      homozygous for a +1444C>T polymorphism in the CRP gene have higher circulating
      concentrations of CRP. Since the distribution of this polymorphism occurs at
      random during gamete formation, its association with coronary events should not
      be biased or confounded. METHODS: We calculated the weighted mean difference in
      CRP between individuals with variants of the +1444C>T polymorphism in the CRP
      gene among 4,659 European men from six studies (genotype-intermediate phenotype
      studies). We used this difference together with data from previous observational
      studies to compute an expected odds ratio (OR) for non-fatal myocardial
      infarction (MI) among individuals homozygous for the T allele. We then performed
      four new genetic association studies (6,201 European men) to obtain a summary OR
      for the association between the +1444C>T polymorphism and non-fatal MI (genotype
      disease studies). RESULTS: CRP was 0.68 mg/l [95% confidence interval (95% CI)
      0.31-1.10; P = 0.0001] higher among subjects homozygous for the +1444-T allele,
      with no confounding by a range of covariates. The expected ORs among TT subjects
      for non-fatal MI corresponding to this difference in CRP was 1.20 (95% CI 1.07
      1.38) using the Reykjavik Heart study data and 1.25 (1.09-1.43) for all
      observational studies to 2004. The estimate for the observed adjusted-OR for non
      fatal MI among TT subjects was 1.01 (95% CI 0.74-1.38), lower than both expected
      ORs. CONCLUSIONS: A common CRP gene polymorphism is associated with important
      differences in CRP concentrations, free from confounding. The null association of
      this variant with coronary events suggests possible residual confounding (or
      reverse causation) in the CRP-coronary event association in observational
      studies, though the confidence limits are still compatible with a modest causal
      effect. Additional studies of genotype (or haplotype) and coronary events would
      help clarify whether or not the link between CRP and coronary events in
      observational studies is causal.

PMID- 16565155
TI  - The reproductive significance of human Fallopian tube cilia.
AB  - Effective tubal transport of ova, sperm and embryos is a prerequisite for
      successful spontaneous pregnancy. Although there is much yet to be discovered
      about the mechanisms involved, it is evident that tubal transit is a far more
      complicated process than initially thought. Propulsion of gametes and embryos is
      achieved by complex interaction between muscle contractions, ciliary activity and
      the flow of tubal secretions. Evidence is accumulating of the important and
      possibly pre-eminent role of ciliary motion in this process; and this review
      describes current knowledge about ciliary activity and its physiological
      regulation. There is also a description of the effects on ciliary function of
      cigarette smoking and various pathological states, including endometriosis and
      microbial infection, with consideration given as to how altered ciliary activity
      may impact upon fertility.

PMID- 16565157
TI  - Treatment of lower urinary tract infection caused by multidrug-resistant extended
      spectrum-beta-lactamase-producing Escherichia coli with amoxicillin/clavulanate:
      case report and characterization of the isolate.

PMID- 16565156
TI  - New variants of the tet(M) gene in Clostridium difficile clinical isolates
      harbouring Tn916-like elements.
AB  - OBJECTIVES: To detect Tn916-like elements in Clostridium difficile clinical
      isolates from different time periods and to analyse the genetic structure of
      these elements, in particular the tet(M) region. METHODS: Ninety C. difficile
      clinical isolates were examined by PCR assays for tet(M) and int, which are
      markers for the Tn916 family of elements. Positive isolates were typed by PCR
      ribotyping, and tetracycline MIC values were evaluated by Etest. The genetic
      organization of the Tn916 elements was investigated by PCR mapping and
      hybridization assays. The tet(M) region of eight selected C. difficile isolates
      was sequenced. RESULTS: Nineteen isolates were tet(M)/int positive and the
      majority (12/19) belonged to PCR-ribotype R, previously found to be predominant
      in clinical strains of more recent isolation. Eleven isolates were tetracycline
      resistant, three inducibly resistant and five susceptible. Fifty-eight per cent
      of the C. difficile isolates harboured one Tn916 element and 42% harboured two.
      Most isolates showed elements with a genetic organization very similar to that of
      Enterococcus faecalis DS16 Tn916. Sequence analysis highlighted variations in the
      leader peptide and six tet(M) variants were identified, five of which have never
      been described before. CONCLUSIONS: C. difficile isolates harbouring Tn916-like
      elements have mainly been isolated since 1997, suggesting a recent circulation of
      these elements among C. difficile strains in Italian hospitals. Molecular
      analysis of these Tn916-like elements showed that they may have different genetic
      structures and carry new tet(M) alleles.

PMID- 16565158
TI  - Impact of diversity of antibiotic use on the development of antimicrobial
      resistance.
AB  - OBJECTIVES: To evaluate the impact of different antibiotic strategies on
      acquisition of resistant microorganisms. METHODS: A prospective study was
      conducted over a 44 month period in a single ICU. Four empirical antibiotic
      strategies for ventilator-associated pneumonia (VAP) were sequentially
      implemented. Over the initial 10 months, patient-specific antibiotic therapy was
      prescribed; then, 4 month periods of prioritization or restriction rotation
      cycles of various antimicrobial agents were implemented for a total of 24 months;
      and, finally, during the last 10 months (mixing period) the first-line antibiotic
      for VAP was changed following a pre-established schedule to ensure maximum
      heterogeneity. Antibiotic consumption was closely monitored every month, and
      antimicrobial resistance patterns were regularly assessed. Antimicrobial
      heterogeneity was estimated using a modified Peterson index (AHI) measuring the
      ratios for the five most used antibiotics. Colonization by targeted
      microorganisms and susceptibility patterns were compared with the patient
      specific period. RESULTS: Higher diversity of antibiotic prescription was
      obtained during patient-specific therapy (AHI = 0.93) or mixing periods (AHI =
      0.95) than during prioritization (AHI = 0.70) or restriction periods (AHI =
      0.68). High homogeneity was associated with increases in carbapenem-resistant
      Acinetobacter baumannii (CR-Ab) [relative risk (RR) 15.5; 95%CI 5.5-42.8],
      extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (RR 4.2;
      95%CI 1.9-9.3) and Enterococcus faecalis (RR 1.7; 95%CI 1.1-2.9). During the
      restriction period, incidence of ESBL-producing Enterobacteriaceae and E.
      faecalis returned to patient-specific rates but CR-Ab remained higher.
      CONCLUSIONS: Antibiotic prescription patterns balancing the use of different
      antimicrobials should be promoted to reduce the selection pressure that aids the
      development of resistance.

PMID- 16565159
TI  - Identification of Tn5397-like and Tn916-like transposons and diversity of the
      tetracycline resistance gene tet(M) in enterococci from humans, pigs and poultry.
AB  - OBJECTIVES: To analyse the sequence diversity of the tetracycline resistance gene
      tet(M) and its location on mobile elements in Enterococcus faecium and
      Enterococcus faecalis from humans, pigs and poultry in Denmark. METHODS: A total
      of 76 isolates were screened for Tn916/Tn1545-like and Tn5397-like transposons
      using PCR. tet(M) was sequenced in 15 of the isolates and compared with tet(M)
      sequences submitted to GenBank (phylogenetic analysis and signs of
      recombination). Plasmids were extracted, filter-mating experiments were performed
      and Tn5397-like transposons were further characterized in selected isolates.
      RESULTS: In 8 of 13 isolates of E. faecium from broilers, tet(M) was present on
      Tn5397-like transposons, whereas tet(M) was predominantly associated with
      Tn916/Tn1545-like transposons in E. faecium from pigs and humans, as well as in
      E. faecalis from humans, pigs and broilers (50 of 63 isolates). The tet(M) genes
      were divided into three major subgroups according to the phylogenetic analysis.
      Subgroup I consisted of tet(M) from Clostridium difficile and E. faecium
      associated with Tn5397-like elements, subgroup II consisted of tet(M) located on
      Tn916/Tn1545 family transposons and subgroup III consisted of tet(M) associated
      with composite elements containing several resistance genes. We found evidence of
      recombination both within and between these groups. Moreover, we identified an E.
      faecium isolate with both Tn916/Tn1545-like and Tn5397-like elements.
      CONCLUSIONS: This study showed that enterococci contain diverse tet(M) genes
      present on different mobile elements, which may suggest that enterococci play an
      important role in the evolution and horizontal spread of mobile elements carrying
      tet(M). This is the first report of Tn5397-like elements in enterococci.

PMID- 16565161
TI  - A profile of alternative RNA splicing and transcript variation of CACNA1H, a
      human T-channel gene candidate for idiopathic generalized epilepsies.
AB  - Highly alternatively spliced genes may provide complex targets for disease
      mutations. Structural changes created by missense mutations may differentially
      affect the activity of alternative gene products, whereas missense, silent and
      non-coding mutations may alter developmental regulation of splice variant
      expression. CACNA1H is a human gene encoding Ca(v)3.2 low-voltage-activated, T
      type calcium channels associated with bursting behavior in neurons and has been
      linked to more than 30 mutations apparently predisposing to childhood absence
      epilepsy (CAE) and other idiopathic generalized epilepsies (IGEs). Biophysical
      properties, including the effects of missense mutations, have been evaluated
      previously for a single splice form of Ca(v)3.2 expressed in transformed cell
      lines. We here show that CACNA1H is alternatively spliced at 12-14 sites, capable
      of generating both functional and non-functional transcripts. Variable
      cytoplasmic and extracellular protein domains point to likely differences in
      gating behavior, sensitivity to neuromodulation and interactions with
      extracellular matrix. Biophysical profiles of selected physiological Ca(v)3.2
      forms reveal variations in kinetics and steady-state gating parameters, most
      likely to affect membrane firing. These were comparable to or larger than changes
      reported for previously studied mutations. Missense CAE and IGE mutations were
      clustered near segments associated with anomalous splicing. Missense and silent
      mutations were found to destroy, create or change the regulatory specificity of
      predicted exonic splicing enhancer sequences that may control splicing
      regulation. We discuss a paradigm for CACNA1H expression of Ca(v)3.2 subunits,
      which may influence future basic and clinical studies.

PMID- 16565160
TI  - Gene targeting of GAN in mouse causes a toxic accumulation of microtubule
      associated protein 8 and impaired retrograde axonal transport.
AB  - Mutations in gigaxonin were identified in giant axonal neuropathy (GAN), an
      autosomal recessive disorder. To understand how disruption of gigaxonin's
      function leads to neurodegeneration, we ablated the gene expression in mice using
      traditional gene targeting approach. Progressive neurological phenotypes and
      pathological lesions that developed in the GAN null mice recapitulate
      characteristic human GAN features. The disruption of gigaxonin results in an
      impaired ubiquitin-proteasome system leading to a substantial accumulation of a
      novel microtubule-associated protein, MAP8, in the null mutants. Accumulated MAP8
      alters the microtubule network, traps dynein motor protein in insoluble
      structures and leads to neuronal death in cultured wild-type neurons, which
      replicates the process occurring in GAN null mutants. Defective axonal transport
      is evidenced by the in vitro assays and is supported by vesicular accumulation in
      the GAN null neurons. We propose that the axonal transport impairment may be a
      deleterious consequence of accumulated, toxic MAP8 protein.

PMID- 16565162
TI  - Subtype-specific inhibition of nicotinic acetylcholine receptors by choline: a
      regulatory pathway.
AB  - Choline is an essential nutrient and a precursor of neurotransmitter
      acetylcholine (ACh) and is produced at synapses during depolarization, upon
      hydrolysis of ACh via acetylcholinesterase, and under conditions of injury and
      trauma. Animal studies have shown that supplementation with choline during early
      development results in long-lasting improvement in memory in adults; however, the
      mechanisms underlying this effect are poorly defined. Previous studies revealed
      that choline interacts with type IA (alpha7*) nicotinic acetylcholine receptors
      (nAChRs) as a full agonist and as a desensitizing agent and is a weak agonist of
      type III (alpha3beta4*) nAChRs. Because nAChRs play a role in learning and memory
      and are generally inhibited by agonists at low concentrations, we investigated in
      this study the inhibitory effects of choline on non-alpha7 nAChRs such as type II
      (alpha4beta2*) and type III nAChRs. Using whole-cell patch-clamp recordings from
      neurons of rat hippocampal and dorsal striatal slices, we demonstrate that
      choline inhibited type III nAChR-mediated glutamate excitatory postsynaptic
      currents (EPSCs). Choline inhibited ACh-induced N-methyl-D-aspartate (NMDA) EPSCs
      in CA1 stratum radiatum (SR) interneurons of rat hippocampal slices with an IC50
      of approximately 15 microM. Choline did not inhibit NMDA or alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid receptors in CA1 SR interneurons. Choline
      inhibited type II nAChRs in CA1 SR interneurons with an IC50 of approximately 370
      microM. The present results reveal an order of inhibitory potency for choline
      type III>type IA>type II nAChRs. It is concluded that brain nAChRs, but not
      glutamate receptors, are the primary targets for the regulatory actions of
      choline.

PMID- 16565163
TI  - Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic
      activity and contractile dysfunction.
AB  - Reactive oxygen species (ROS), including H2O2, cause intracellular calcium
      overload and ischemia-reperfusion damage. The objective of this study was to
      examine the hypothesis that H2O2-induced arrhythmic activity and contractile
      dysfunction are the results of an effect of H2O2 to increase the magnitude of the
      late sodium current (late INa). Guinea pig and rabbit isolated ventricular
      myocytes were exposed to 200 microM H2O2. Transmembrane voltages and currents and
      twitch shortening were measured using the whole-cell patch-clamp technique and
      video edge detection, respectively. [Na+]i and [Ca2+]i were determined by
      fluorescence measurements. H2O2 caused a persistent late INa that was almost
      completely inhibited by 10 microM tetrodotoxin (TTX). H2O2 prolonged the action
      potential duration (APD), slowed the relaxation rate of cell contraction, and
      induced early afterdepolarizations (EADs) and aftercontractions. H2O2 also caused
      increases of [Na+]i and [Ca2+]i. Ranolazine (10 microM), a novel inhibitor of
      late INa, attenuated H2O2-induced late INa by 51+/-9%. TTX (2 microM) or 10
      microM ranolazine attenuated H2O2-induced APD prolongation and suppressed EADs.
      Ranolazine accelerated the twitch relaxation rate in the presence of H2O2 and
      abolished H2O2-induced aftercontractions. Pretreatment of myocytes with
      ranolazine delayed and reduced the increases of APD, [Na+]i, and [Ca2+]i caused
      by H2O2. In conclusion, the results confirm the hypothesis that an increase in
      late INa during exposure of ventricular myocytes to H2O2 contributes to
      electrical and contractile dysfunction and suggest that inhibition of late INa
      may offer protection against ROS-induced Na+ and Ca2+ overload.

PMID- 16565164
TI  - Buprenorphine activates mu and opioid receptor like-1 receptors simultaneously,
      but the analgesic effect is mainly mediated by mu receptor activation in the rat
      formalin test.
AB  - Buprenorphine is a mixed opioid receptor agonist-antagonist. Recently,
      buprenorphine was reported to act as an agonist to opioid receptor like-1 (ORL1)
      receptor. In the present study, we examined the role of spinal and supraspinal mu
      receptors and spinal and supraspinal ORL1 receptors in producing an analgesic
      effect by intrathecal (i.t.), intracerebroventricular (i.c.v.), or i.p.
      administration of buprenorphine in the rat formalin test. Male rats were prepared
      with i.t. catheters or i.c.v. injection cannulas. The paw formalin injection (50
      microl of 5% formalin) induces biphasic flinching (phase 1, 0-6 min; phase 2, 10
      60 min) of the injected paw. Buprenorphine, naloxone (a mu-opioid receptor
      antagonist), or (1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3
      ethyl-1,3-dihydro-2H-benzimidazol-2-one (J113397) (an ORL1 receptor-selective
      antagonist) was administered i.t., i.c.v., or i.p.. Intrathecal, i.c.v., or i.p.
      injection of buprenorphine produces an analgesic effect in a dose-dependent
      manner. The effect of i.c.v. buprenorphine was antagonized by i.c.v. naloxone or
      i.c.v. J113397, and the effect of i.t. buprenorphine was antagonized by i.t.
      naloxone or i.t. J113397. The effect of i.p. buprenorphine was antagonized by
      i.p. or i.t. naloxone but not by i.c.v. naloxone. The analgesic effect of i.p.
      buprenorphine was enhanced by i.p. J113397 or i.c.v. J113397. Intraperitoneal,
      but not i.t. or i.c.v., buprenorphine decreased the number of Fos-like
      immunoreactivity positive neurons in the L4-L5 spinal dorsal horn. These data
      indicated that buprenorphine affects nociceptive processing by acting at both
      supraspinal and spinal mu and ORL1 receptors. The analgesic effect of
      systemically administered buprenorphine was suppressed by the concomitant
      activation of supraspinal ORL1 receptor.

PMID- 16565165
TI  - Augmented endothelium-derived hyperpolarizing factor-mediated relaxations
      attenuate endothelial dysfunction in femoral and mesenteric, but not in carotid
      arteries from type I diabetic rats.
AB  - Individual vascular beds exhibit differences in vascular reactivity. The present
      study investigates the effects of streptozotocin-induced type I diabetes on
      endothelium-dependent responses of rat carotid, femoral, and mesenteric arteries.
      Rings with and without endothelium, suspended in organ chambers for isometric
      tension recording, were contracted with phenylephrine and exposed to increasing
      concentrations of acetylcholine. In carotid and femoral arteries, acetylcholine
      produced concentration- and endothelium-dependent relaxations that were abolished
      by Nomega-nitro-L-arginine methyl ester (L-NAME; specific nitric-oxide synthase
      inhibitor) and were impaired slightly in preparations from streptozotocin-treated
      rats (STZ-rats). This impairment could be prevented by L-arginine. In femoral
      arteries incubated with L-NAME, acetylcholine caused endothelium-dependent
      contractions that were abolished by 3-[(6-amino-(4-chlorobenzensulfonyl)-2-methyl
      5,6,7,8-tetrahydronapht]-1-yl) propionic acid (S18886) (antagonist of thromboxane
      A2/prostaglandins H2-receptors) and reversed to relaxation by indomethacin
      (inhibitor of cyclooxygenase). The latter relaxation was inhibited by
      charybdotoxin plus apamin, suggesting a role of endothelium-dependent
      hyperpolarizing factor (EDHF). This EDHF-mediated component was augmented
      slightly in arteries from STZ-rats. In mesenteric arteries, relaxations to
      acetylcholine were only partially inhibited by L-NAME, and the L-NAME-resistant
      component was abolished by charybdotoxin plus apamin. In the mesenteric arteries
      from STZ-rats, L-NAME-sensitive relaxations to acetylcholine were reduced and the
      EDHF-component was augmented. These findings demonstrate a marked heterogeneity
      in endothelium-dependent responses in rat arteries and their differential
      adaptation in the course of type I diabetes. In particular, the EDHF-mediated
      component not only compensates for the reduced bioavailability of nitric oxide in
      the femoral and mesenteric artery but also counteracts the augmented endothelium
      dependent contractions in the former.

PMID- 16565166
TI  - Induction of heme oxygenase-1 is involved in carbon monoxide-mediated central
      cardiovascular regulation.
AB  - Carbon monoxide (CO) has been identified as an endogenous biological messenger in
      the brain. Heme oxygenase (HO) catalyzes the metabolism of heme to CO and
      biliverdin. Previously, we have shown the involvement of CO in central
      cardiovascular regulation, baroreflex modulation, and glutaminergic neuro
      transmission in the nucleus tractus solitarii (NTS) of rats. In this study, we
      examined which HO isoform could be induced after hemin injection in the NTS. We
      also investigated their in situ distributions in the NTS after induction. Male
      Sprague-Dawley rats were anesthetized with urethane, and blood pressure was
      monitored intra-arterially. Unilateral microinjection of hemin (1 nmol), a heme
      molecule cleaved by HO to yield CO, produced significant decrease in blood
      pressure and heart rate. These cardiovascular effects of hemin were attenuated by
      prior administration of HO inhibitor zinc protoporphyrin IX (ZnPPIX).
      Microinjection of hemin into NTS resulted in significant induction of HO-1
      protein expression in situ. Pretreatment of ZnPPIX significantly inhibited the HO
      1 induction after hemin injection. No significant changes of HO-2 expression were
      found after hemin injection and ZnPPIX pretreatment. The in situ inductions of
      the HO-1 protein expression were further confirmed to be in glial cells and
      neurons after hemin injections into the NTS. These results indicated HO-1 but not
      HO-2 might be responsible for the generation of CO and contribute to central
      control of cardiovascular effects.

PMID- 16565167
TI  - Antinociceptive pharmacology of N-[[4-(4,5-dihydro-1H-imidazol-2
      yl)phenyl]methyl]-2-[2-[[(4-methoxy-2,6-dimethylphenyl)
      sulfonyl]methylamino]ethoxy]-N-methylacetamide, fumarate (LF22-0542), a novel
      nonpeptidic bradykinin B1 receptor antagonist.
AB  - The antinociceptive pharmacology of N-[[4-(4,5-dihydro-1H-imidazol-2
      yl)phenyl]methyl]-2-[2-[[(4-methoxy-2,6-dimethylphenyl)
      sulfonyl]methylamino]ethoxy]-N-methylacetamide fumarate (LF22-0542), a novel
      nonpeptidic B1 antagonist, was characterized. LF22-0542 showed high affinity for
      human and mouse B1 receptors with virtually no affinity for the human B2
      receptor; a selectivity index of at least 4000 times was obtained when LF22-0542
      was profiled throughout binding or cell biology assays on 64 other G-protein
      coupled receptor, 10 ion channels, and seven enzymes. LF22-0542 was a competitive
      B1 receptor antagonist and elicited significant antinociceptive actions in the
      mouse acetic acid-induced writhing assay, as well as in the second phases of
      formalin-induced nociception in mice and in both the first and second phases of
      the formalin response in rats. LF22-0542 was active after s.c. but not p.o.
      administration. In B1 receptor knockout (KO) mice, acetic acid and formalin
      responses were significantly reduced and LF22-0542 had no additional effects in
      these animals. LF22-0542 alleviated thermal hypersensitivity in both acute
      (carrageenan) and persistent inflammatory (complete Freund's adjuvant) pain
      models in rats. LF22-0542 produced a full reversal of experimental neuropathic
      thermal hypersensitivity but was inactive in reversing nerve injury-induced
      tactile hypersensitivity in rats. In agreement with this observation, B1 KO mice
      subjected to peripheral nerve injury did not show thermal hypersensitivity but
      developed nerve injury-induced tactile hypersensitivity normally. The data
      demonstrate the antihyperalgesic actions of a selective systemically administered
      B1 receptor antagonist and suggest the utility of this class of agents for the
      treatment of inflammatory pain states and for some aspects of neuropathic pain.

PMID- 16565168
TI  - Differential modulation of Cav1.2 and Cav1.3-mediated glucose-stimulated insulin
      secretion by cAMP in INS-1 cells: distinct roles for exchange protein directly
      activated by cAMP 2 (Epac2) and protein kinase A.
AB  - Using insulin-secreting cell line (INS)-1 cells stably expressing dihydropyridine
      insensitive mutants of either Cav1.2 or Cav1.3, we previously demonstrated that
      Cav1.3 is preferentially coupled to insulin secretion and [Ca2+]i oscillations
      stimulated by 11.2 mM glucose. Using the same system, we found that insulin
      secretion in 7.5 mM glucose plus 1 mM 8-bromo-cAMP (8-Br-cAMP) is mediated by
      both Cav1.2 and Cav1.3. Treatment of INS-1 cells or INS-1 cells stably expressing
      Cav1.2/dihydropyridine-insensitive (DHPi) channels in the presence of 10 microM
      nifedipine, with effector-specific cAMP analogs 8-(4-chlorophenylthio)-2'-O
      methyladenosine-cAMP [8-pCPT-2'-O-Me-cAMP; 100 microM; Exchange Protein directly
      Activated by cAMP 2 (Epac2)-selective] or N6-benzoyl-cAMP [50 microM; Protein
      Kinase A (PKA)-selective] partially increased insulin secretion. Secretion
      stimulated by a combination of the two cAMP analogs was additive and comparable
      with that stimulated by 1 mM 8-Br-cAMP. In INS-1 cells stably expressing
      Cav1.3/DHPi in the presence of 10 microM nifedipine, N6-benzoyl-cAMP, but not 8
      pCPT-2'-O-Me-cAMP, significantly increased glucose-stimulated insulin secretion.
      However, the combination of N6-benzoyl-cAMP and 8-pCPT-2'-O-Me-cAMP significantly
      increased glucose-stimulated secretion compared with N6-benzoyl-cAMP alone. In
      INS-1 cells, 8-Br-cAMP potentiation of insulin secretion in 7.5 mM glucose is
      blocked by thapsigargin (1 microM) and ryanodine (0.5 microM). In contrast,
      ryanodine has no effect on insulin secretion or [Ca2+]i oscillations stimulated
      by 11.2 mM glucose in INS-1 cells. Our data suggest that both Cav1.2 and Cav1.3
      mediate insulin secretion stimulated by 7.5 mM glucose and cAMP via a mechanism
      that requires internal stores of Ca2+. Furthermore, cAMP modulation of secretion
      mediated by Cav1.2 seems to involve both Epac2 and PKA independently. In
      contrast, cAMP modulation of Cav1.3-mediated secretion depends upon PKA
      activation, whereas the contribution of Epac2 is dependent upon PKA activation.

PMID- 16565169
TI  - Physiological and biophysical factors that influence Alzheimer's disease amyloid
      plaque targeting of native and putrescine modified human amyloid beta40.
AB  - Amyloid beta40 (Abeta40) and its derivatives are being developed as probes for
      the ante-mortem diagnosis of Alzheimer's disease. Putrescine-Abeta40 (PUT
      Abeta40) showed better plaque targeting than the native Abeta40, which was not
      solely explained by the differences in their blood-brain-barrier (BBB)
      permeabilities. The objective of this study was to elucidate the physiological
      and biophysical factors influencing the differential targeting of Abeta40 and PUT
      Abeta40. Despite better plaque-targeting ability 125I-PUT-Abeta40 was more
      rapidly cleared from the systemic circulation than amyloid beta40 labeled with
      125I (125I-Abeta40) after i.v. administration in mice. The BBB permeability of
      both compounds was inhibited by circulating peripheral Abeta40 levels. 125I
      Abeta40 but not 125I-PUT-Abeta40 was actively taken up by the mouse brain slices
      in vitro. Only fluorescein-Abeta40, not fluorescein-PUT-Abeta40, was localized in
      the brain parenchymal cells in vitro. The metabolism of 125I-Abeta40 in the brain
      slices was twice as great as 125I-PUT-Abeta40. 125I-Abeta40 efflux from the brain
      slices was saturable and found to be 5 times greater than that of 125I-PUT
      Abeta40. Thioflavin-T fibrillogenesis assay demonstrated that PUT-Abeta40 has a
      greater propensity to form insoluble fibrils compared with Abeta40, most likely
      due to the ability of PUT-Abeta40 to form beta sheet structure more readily than
      Abeta40. These results demonstrate that the inadequate plaque targeting of
      Abeta40 is due to cellular uptake, metabolism, and efflux from the brain
      parenchyma. Despite better plaque targeting of PUTAbeta40, its propensity to form
      fibrils may render it less suitable for human use and thus allow increased focus
      on the development of novel derivatives of Abeta with improved characteristics.

PMID- 16565170
TI  - N-methylpurine DNA glycosylase and 8-oxoguanine dna glycosylase metabolize the
      antiviral nucleoside 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole.
AB  - The rapid in vivo degradation of the potent human cytomegalovirus inhibitor 2
      bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) compared with a
      structural L-analog, maribavir (5,6-dichloro-2-(isopropylamino)-1-beta-L
      ribofuranosyl-1H-benzimidazole), has been attributed to selective glycosidic bond
      cleavage. An enzyme responsible for this selective BDCRB degradation, however,
      has not been identified. Here, we report the identification of two enzymes, 8
      oxoguanine DNA glycosylase (OGG1) and N-methylpurine DNA glycosylase (MPG), that
      catalyze N-glycosidic bond cleavage of BDCRB and its 2-chloro homolog, 2,5,6
      trichloro-1-(beta-D-ribofuranosyl)benzimidazole, but not maribavir. To our
      knowledge, this is the first demonstration that free nucleosides are substrates
      of OGG1 and MPG. To understand how these enzymes might process BDCRB, docking and
      molecular dynamics simulations were performed with the native human OGG1 crystal
      coordinates. These studies showed that OGG1 was not able to bind a negative
      control, guanosine, yet BDCRB and maribavir were stabilized through interactions
      with various binding site residues, including Phe319, His270, Ser320, and Asn149.
      Only BDCRB, however, achieved orientations whereby its anomeric carbon, C1',
      could undergo nucleophilic attack by the putative catalytic residue, Lys249.
      Thus, in silico observations were in perfect agreement with experimental
      observations. These findings implicate DNA glycosylases in drug metabolism.

PMID- 16565171
TI  - Biotransformation of fluticasone: in vitro characterization.
AB  - Fluticasone propionate (FTP) is a synthetic trifluorinated glucocorticoid with
      potent anti-inflammatory action that is commonly used in patients with asthma.
      After oral or intranasal administration, FTP undergoes rapid hepatic
      biotransformation; the principal metabolite formed is a 17beta-carboxylic acid
      derivative (M1). M1 formation has been attributed largely to cytochrome P450 3A4
      (CYP3A4); however, there are no published data that confirm this assertion.
      Hence, in vitro studies were conducted to determine the role that human P450s
      play in the metabolism of FTP. Consistent with in vivo data, human liver
      microsomes catalyzed the formation of a single metabolite (M1) at substrate
      concentrations <or=10 microM (mean plasma Cmax = 1 nM). Under these conditions,
      the kinetics of M1 formation in human liver microsomes were consistent with those
      of a single enzyme (Km congruent with 5 microM). Formation of M1 correlated
      significantly (r > 0.95) with CYP3A4/5 activities in a panel of human liver
      microsomes (n = 14) and was markedly impaired by the CYP3A inhibitor ketoconazole
      (>94%) but not by inhibitors of other P450 enzymes (<or=10%). Studies with a
      panel of cDNA-expressed enzymes revealed that M1 formation was catalyzed
      primarily by CYP3A enzymes at FTP concentrations <or=1 microM. M1 formation was
      catalyzed by P450s 3A4, 3A5, and 3A7; in vitro intrinsic clearance values
      (Vmax/Km) were comparable for all three CYP3A enzymes. These results suggest that
      at pharmacologically relevant concentrations, biotransformation of FTP to M1 is
      mediated predominantly by CYP3A enzymes in the liver.

PMID- 16565172
TI  - Comparison of mouse and rat cytochrome P450-mediated metabolism in liver and
      intestine.
AB  - The liver is considered to be the major site of first-pass metabolism, but the
      small intestine is also able to contribute significantly. The improvement of
      existing in vitro techniques and the development of new ones, such as intestinal
      slices, allow a better understanding of the intestine as a metabolic organ. In
      this paper, the formation of metabolites of several human CYP3A substrates by
      liver and intestinal slices from rat and mouse was compared. The results show
      that liver slices exhibited a higher metabolic rate for the majority of the
      studied substrates, but some metabolites were produced at a higher rate by
      intestinal slices, compared with liver slices. Coincubation with ketoconazole
      inhibited the metabolic conversion in intestinal slices almost completely, but
      inhibition was variable in liver slices. To better understand the role of CYP3A
      in mice, we studied the relative mRNA expression of different CYP3A isoforms in
      intestine and liver from mice because, in this species, CYP3A expression has not
      been well described in these organs. It was found that in mice, CYP3A13 is more
      expressed in the intestine, whereas CYP3A11, CYP3A25, and CYP3A41 are more
      expressed in the liver, comparable to similar findings in the rat. Altogether,
      these data demonstrate that, in addition to liver, the intestine from mouse and
      rat may have an important role in the process of first-pass metabolism, depending
      on the substrate. Moreover, we show that intestinal slices are a useful in vitro
      technique to study gut metabolism.

PMID- 16565173
TI  - Saturable binding of indisulam to plasma proteins and distribution to human
      erythrocytes.
AB  - The anticancer agent indisulam has a nonlinear pharmacokinetic profile, which may
      be partly related to saturable binding to blood constituents. To gain insight
      into the complex nonlinear behavior of indisulam, we investigated binding to
      plasma proteins and erythrocytes. The purpose of the study was to develop a
      physiological model for the distribution of indisulam in blood. Concentrations of
      radiolabeled indisulam were measured in vitro 1) in total plasma and in
      ultrafiltrate to investigate plasma protein binding, 2) in erythrocytes and in
      plasma to investigate distribution to erythrocytes, and 3) in erythrocyte
      membranes to investigate nonspecific binding in erythrocytes. For in vivo
      assessment, 21 patients received 400 to 900 mg/m2 indisulam in a 1- or 2-h
      infusion. Total and free concentrations in plasma and concentrations in
      erythrocytes were determined at multiple time points. In vitro plasma protein
      binding was described by a Langmuir model with a maximal binding capacity (Bmax =
      767 microM) and an equilibrium dissociation constant (KD = 1.02 microM). The
      maximal capacity of plasma protein binding in vivo corresponded to albumin
      levels. The bound concentration in erythrocytes was described by a two-site
      model, comprising a saturable and a nonspecific binding component. The saturable
      component (Bmax = 174 microM) may correspond to binding to carbonic anhydrase.
      The physiological model adequately described the nonlinear disposition of
      indisulam in whole blood. Indisulam was bound to plasma proteins and distributed
      to erythrocytes in a saturable manner. These saturable processes may be
      attributed to binding to albumin (in plasma) and to carbonic anhydrase (in
      erythrocytes).

PMID- 16565175
TI  - The future of academic health centers.

PMID- 16565176
TI  - Managing resources in a better way: a new financial management approach for the
      University of Michigan Medical School.
AB  - Responding to changing trends in how the University of Michigan Medical School
      (UMMS) has been traditionally financed and anticipating that these trends will
      continue, in 2002 the executive leadership at the UMMS embarked upon a course
      designed to change not only the school's financial structure but its management
      culture as well. Changing traditional ways of thinking about budgets and
      developing a set of key performance indicators that demonstrate how certain
      activities shape the use of resources has brought greater understanding of how to
      optimize those resources to the greatest extent. Through internally developed Web
      based software applications called M-STAT, M-DASH and M-ALERT (which are
      strategic reporting tools that the author describes), the UMMS now can manage
      resources in a completely different way. These tools are used to spot general
      financial trends or examine a more specific financial element (such as trends in
      grant funding or clinical activity), track the utilization of research space,
      calculate the break-even cost of research space, and most important, model
      various "what-if" scenarios to help plan effectively for the future needs of the
      UMMS. The strategic reporting system is still being integrated throughout the
      UMMS, so there has not yet been time to measure the system's efficacy or its
      shortcomings. Nevertheless, important lessons have already been learned, which
      the author presents.

PMID- 16565174
TI  - In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine
      valproic acid interaction.
AB  - Studies were performed to investigate the UDP-glucuronosyltransferase enzyme(s)
      responsible for the human liver microsomal N2-glucuronidation of the
      anticonvulsant drug lamotrigine (LTG) and the mechanistic basis for the LTG
      valproic acid (VPA) interaction in vivo. LTG N2-glucuronidation by microsomes
      from five livers exhibited atypical kinetics, best described by a model
      comprising the expressions for the Hill (1869 +/- 1286 microM, n = 0.65 +/- 0.16)
      and Michaelis-Menten (Km 2234 +/- 774 microM) equations. The UGT1A4 inhibitor
      hecogenin abolished the Michaelis-Menten component, without affecting the Hill
      component. LTG N2-glucuronidation by recombinant UGT1A4 exhibited Michaelis
      Menten kinetics, with a Km of 1558 microM. Although recombinant UGT2B7 exhibited
      only low activity toward LTG, inhibition by zidovudine and fluconazole and
      activation by bovine serum albumin (BSA) (2%) strongly suggested that this enzyme
      was responsible for the Hill component of microsomal LTG N2-glucuronidation. VPA
      (10 mM) abolished the Hill component of microsomal LTG N2-glucuronidation,
      without affecting the Michaelis-Menten component or UGT1A4-catalyzed LTG
      metabolism. Ki values for inhibition of the Hill component of LTG N2
      glucuronidation by VPA were 2465 +/- 370 microM and 387 +/- 12 microM in the
      absence and presence, respectively, of BSA (2%). Consistent with published data
      for the effect of fluconazole on zidovudine glucuronidation by human liver
      microsomal UGT2B7, the Ki value generated in the presence of BSA predicted the
      magnitude of the LTG-VPA interaction reported in vivo. These data indicate that
      UGT2B7 and UGT1A4 are responsible for the Hill and Michaelis-Menten components,
      respectively, of microsomal LTG N2-glucuronidation, and the LTG-VPA interaction
      in vivo arises from inhibition of UGT2B7.

PMID- 16565179
TI  - The overhead page.

PMID- 16565178
TI  - Improving clinical productivity in the academic setting: a novel incentive plan
      based on utility theory.
AB  - PURPOSE: Academic internal medicine practices face growing challenges to
      financial viability due to high overhead, competing institutional missions, and
      suboptimal physician productivity. The authors describe the development of a
      clinical incentive plan for a group of academic subspecialty physicians at the
      Dana Clinic, an outpatient setting at Yale School of Medicine, and report on
      results of the first year's experience under the plan. METHOD: Utility theory was
      used to assess the risk profile of clinic faculty and identify incentive payments
      that would optimize faculty benefit or "utility" while minimizing departmental
      costs. Under the plan, physicians who reached a productivity target based on work
      Relative Value Units (wRVUs) between October 2003 and November 2004 had overhead
      costs covered and received a fixed payment to support salary; additional
      incentive payments were available for those exceeding the target. Physicians
      failing to reach the target were responsible for their own overhead costs and
      received no fixed payment. Physician productivity as measured by wRVU per full
      time equivalent (FTE) was compared for the year prior to, and the year following,
      incentive plan introduction. RESULTS: Forty-seven members of eight academic
      sections were included in the analysis. Median productivity improved by 34%, with
      42 of 47 physicians showing improvement. Significant improvements were also noted
      in collections (62%) and visit volume (23%), and shifts were observed in coding
      patterns. CONCLUSIONS: The unique threshold-based structure of the incentive
      plan, as determined through utility theory modeling, as well as permitting
      physicians to choose how to achieve the wRVU target were key features of its
      success, resulting in improved productivity without increasing practice resources
      or faculty salaries.

PMID- 16565180
TI  - The incorporation of patient safety into board certification examinations.
AB  - In response to growing recognition of the importance of patient safety in the
      practice of medicine, the American Board of Medical Specialties (ABMS) is
      encouraging its individual specialty member boards to introduce material on
      patient safety into certification examinations. Certification and recertification
      candidates, medical schools, and residency programs will likely need to prepare
      for the possibility that upcoming examinations will include patient safety. Due
      to the relative youth of the patient safety movement, some may ask whether the
      field is sufficiently developed and, if so, ask what would be fair to ask
      candidates to know. To determine what subject matter could be reliably tested,
      the ABMS and the Council of Medical Specialty Societies convened a panel of
      patient safety experts in 2003. Based on the panel's recommendations, the authors
      provide a brief summary of the panel's findings and an overview of current
      concepts in patient safety. The authors also explore which current concepts of
      patient safety candidates may reasonably expect to find on upcoming examinations.

PMID- 16565181
TI  - Contingency plans and the sniffles.

PMID- 16565182
TI  - Developing an interdisciplinary, community-based education program for health
      professions students: the Rochester experience.
AB  - To successfully meet the nation's changing health needs, future health
      professionals must learn skills in applied health promotion and disease
      prevention. To achieve these goals, the Center for Rochester's Health (the
      Center), a collaboration of the Monroe County Department of Public Health and the
      University of Rochester School of Medicine and Dentistry and School of Nursing,
      all located in Rochester, New York, developed an innovative education program
      that gives interdisciplinary teams of students opportunities to partner with
      community agencies engaged in research-oriented health improvement initiatives.
      The Center started this course in 1998, under the auspices of a national
      initiative supported by the Health Resources and Services Administration and the
      Institute for Healthcare Improvement. The authors discuss the challenges related
      to the implementation and institutionalization of this interdisciplinary
      population-based education program. They describe their experiences over a seven
      year period, from 1998 to 2005, including the various factors that enabled them
      to make necessary changes in the program activities and the ways in which the
      Center was able to bring departments together to consider new course directions
      for engaging students in the community health improvement process. They discuss
      the different stages of program development, including the early years of program
      planning and later curriculum changes that involved the development of an online
      population health curriculum. The authors conclude that by understanding changes
      in the education goals of various health professions schools and by adapting
      education programs to meet the needs of students from these schools, program
      planners will have more opportunities to sustain community-based education
      programs.

PMID- 16565183
TI  - Silhouette of pain.

PMID- 16565184
TI  - An innovative program to augment community preceptors' practice and teaching
      skills.
AB  - Medical students currently interface more and more with community-based
      physicians, many of whom have little training or experience as educators. They
      also start their ambulatory experiences from the beginning of their medical
      school training, not just at the clerkship year. This has prompted substantial
      literature on the need for improved faculty development for community preceptors,
      which is widely believed to be inadequate at present. The authors describe a
      novel program, designed to augment community preceptor teaching skills and
      practice behaviors, focusing on topics relating to humanism, communication, and
      psychosocial issues common in primary care. The program was conducted for four
      years beginning in 1999 and organized around acknowledged attributes of
      successful adult learning, and used case-based, small-group sessions, where
      individual community preceptors were each asked to "teach" a series of
      standardized students, in front of the group, regarding issues raised by a number
      of hypothetical patient cases. The standardized students had in turn been trained
      by the authors to interact with the participating faculty in a defined manner.
      The small-group sessions were led by community "opinion leaders" who had been
      chosen for this role by the participants, and who themselves first underwent
      training by the authors to familiarize them with core concepts felt to be
      essential to the program. At the conclusion of the entire process, surveys of the
      opinion leaders, the other community preceptor participants, and the standardized
      students suggested that the program did stimulate significant changes in attitude
      and behavior, although further research is needed to confirm this.

PMID- 16565185
TI  - The impact of preclinical preceptorships on learning the fundamentals of clinical
      medicine and physical diagnosis skills.
AB  - PURPOSE: To learn whether preclinical primary care preceptorships resulted in
      demonstrable clinical performance benefits to medical students. METHOD: This was
      a retrospective cohort study of 267 medical students who elected and 310 students
      who did not elect to take a four-week primary care preceptorship following the
      first year of training at the University of Texas Medical School at Houston in
      2001-2003. Outcome variables were the students' performances on a written
      examination testing their integration of basic science and fundamentals of
      clinical medicine and performances on a comprehensive objective structured
      clinical examination (OSCE). After adjusting for factors that might have
      explained differences in the students' performances, logistic regression models
      were used to assess the association of the outcome variables with participation
      in a preceptorship. RESULTS: Students who participated in any one of the
      preceptorships performed better on the OSCE and on the fundamentals of clinical
      medicine examination than students who did not participate (p < .01). Students
      who participated in the family medicine or pediatric preceptorship scored higher
      on an OSCE (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.01-2.78 and
      OR, 2.26; 95% CI, 1.18-4.36, respectively) than those students who did not
      participate in a preceptorship. Students who participated in the internal
      medicine preceptorship scored higher on the fundamentals of clinical medicine
      examination (OR, 3.18; 95% CI, 1.92-5.23). CONCLUSIONS: Preliminary evidence
      indicates that a short preclinical primary care preceptorship can help medical
      students to consolidate and integrate the fundamental cognitive and clinical
      skills they will apply during the clinical years of medical training.

PMID- 16565186
TI  - From physician-centered to community-oriented perspectives on health care:
      assessing the efficacy of community-based training.
AB  - PURPOSE: To understand the influence of a community-based child advocacy block
      rotation on the perspectives of first-year pediatric residents and whether this
      influence persists. METHOD: The authors conducted semistructured interviews to
      assess the impact of the training program on pediatrics residents' perspectives
      regarding child advocacy and their understanding of the role of the community
      members and community-based assets in child advocacy. Three cohorts of first-year
      residents at the University of California, Davis, participated in the two-week
      community collaborative rotation from 2000 03. Two cohorts of 23 first-year
      residents were interviewed. In 2003, the first cohort of nine third-year
      residents was re-interviewed to assess long-term impact. Interviews were
      conducted before and after residents' experiences with community collaboratives.
      Transcripts of interviews were reviewed using an iterative process, and a coding
      system was applied using a qualitative software program. RESULTS: Comparison of
      pre- and postrotation interview data showed that residents' conceptions of
      advocacy shifted from ideas about being a pediatrician for the community to being
      a pediatrician in the community. This change in definition reflected a view of
      the pediatrician as facilitator, a community asset, rather than as a central
      administrator of child health affairs. This shift persisted through the
      completion of residency. CONCLUSIONS: These findings suggest that substantive
      interaction in a community collaborative can provide a starting point for
      residents to reconceptualize their role as pediatrician, for understanding the
      diverse contexts characteristic of children's circumstances, and for identifying
      and using community-based assets for improving child health. Definition changes
      persisted through residency and may influence residents' future behavior in
      clinical practice.

PMID- 16565188
TI  - Systematic review of depression, anxiety, and other indicators of psychological
      distress among U.S. and Canadian medical students.
AB  - PURPOSE: To systematically review articles reporting on depression, anxiety, and
      burnout among U.S. and Canadian medical students. METHOD: Medline and PubMed were
      searched to identify peer-reviewed English-language studies published between
      January 1980 and May 2005 reporting on depression, anxiety, and burnout among
      U.S. and Canadian medical students. Searches used combinations of the Medical
      Subject Heading terms medical student and depression, depressive disorder major,
      depressive disorder, professional burnout, mental health, depersonalization,
      distress, anxiety, or emotional exhaustion. Reference lists of retrieved articles
      were inspected to identify relevant additional articles. Demographic information,
      instruments used, prevalence data on student distress, and statistically
      significant associations were abstracted. RESULTS: The search identified 40
      articles on medical student psychological distress (i.e., depression, anxiety,
      burnout, and related mental health problems) that met the authors' criteria. No
      studies of burnout among medical students were identified. The studies suggest a
      high prevalence of depression and anxiety among medical students, with levels of
      overall psychological distress consistently higher than in the general population
      and age-matched peers by the later years of training. Overall, the studies
      suggest psychological distress may be higher among female students. Limited data
      were available regarding the causes of student distress and its impact on
      academic performance, dropout rates, and professional development. CONCLUSIONS:
      Medical school is a time of significant psychological distress for physicians-in
      training. Currently available information is insufficient to draw firm
      conclusions on the causes and consequences of student distress. Large,
      prospective, multicenter studies are needed to identify personal and training
      related features that influence depression, anxiety, and burnout among students
      and explore relationships between distress and competency.

PMID- 16565189
TI  - Personal life events and medical student burnout: a multicenter study.
AB  - PURPOSE: Burnout, a marker of professional distress prevalent among residents and
      physicians, has been speculated to originate in medical school. Little is known
      about burnout in medical students. The authors sought to identify the prevalence
      of burnout, variation of its prevalence during medical school, and the impact of
      personal life events on burnout and other types of student distress. METHOD: All
      medical students (n = 1,098) attending the three medical schools in Minnesota
      were surveyed in spring 2004 using validated instruments to assess burnout,
      quality of life, depression, and alcohol use. Students were also asked about the
      prevalence of positive and negative personal life events in the previous 12
      months. RESULTS: A total of 545 medical students (response rate 50%) completed
      the survey. Burnout was present in 239 (45%) of medical students. While the
      frequency of a positive depression screen and at-risk alcohol use decreased among
      more senior students, the frequency of burnout increased (all p < .03). The
      number of negative personal life events in the last 12 months also correlated
      with the risk of burnout (p = .0160). Personal life events demonstrated a
      stronger relationship to burnout than did year in training on multivariate
      analysis. CONCLUSIONS: Burnout appears common among U.S. medical students and may
      increase by year of schooling. Despite the notion that burnout is primarily
      linked to work-related stress, personal life events also demonstrated a strong
      relationship to professional burnout. The authors' findings suggest both personal
      and curricular factors are related to burnout among medical students. Efforts to
      decrease burnout must address both of these elements.

PMID- 16565191
TI  - Medicine and the arts. Les Miserables by Victor Hugo. Commentary.

PMID- 16565192
TI  - Teaching medical students about different health care systems: an international
      exchange program.
AB  - Understanding how different health care systems are organized and financed is
      rarely taught in medical school. In 1997, several U.S. and European medical
      schools formed an ongoing, innovative, and collaborative exchange program to
      enable their medical students to gain an insight into the dynamics of another
      country's health care system. One student from each participating institution
      completes a month-long rotation at a host medical school under the supervision of
      a faculty mentor. Selected target diagnoses serve as the basis for comparative
      case studies. To enable the student to effectively study the host country's
      health care system, each is assigned a patient with the preselected specific
      diagnosis. The students view the patient's care within the context of the host
      country's delivery system rather than being limited to the clinical diagnosis and
      treatment of the disease. Matching the student with a patient permits the student
      to see how medical care is delivered and financed in the host country. Each
      student is required to prepare a written report focusing on costs; organization
      and delivery of care; quality and outcomes of care; politics, culture, and
      ethics; and learning. The case studies permit comparisons of health care systems
      among the participating U.S. and European Union countries, as well as
      opportunities for institutional and individual learning.

PMID- 16565193
TI  - Commentary: Health systems and health policy: a curriculum for all medical
      students.
AB  - A companion article in this issue of Academic Medicine provides an example of a
      method for electively integrating health systems and health policy issues into
      medical education. However, a curriculum in health systems and health policy is
      crucial to the education of all future physicians and other health professionals.
      The Clinical Prevention and Population Health Curriculum Framework of the Healthy
      People Curriculum Task Force has recently recommended a health systems and health
      policy curriculum that includes the domains of organization of clinical and
      public health systems; health services financing; health workforce; and health
      policy process. The curriculum should commence prior to year three and continue
      in years three and four so that students have a framework for integrating and
      subsequently sharing their experiences. Current Liaison Committee on Medical
      Education data indicate that on average less than 70% of medical schools require
      any curriculum in these four domains and only 40% of medical schools include all
      four of these domains in their required curriculum. Incorporation all of these
      domains into well-defined, required curricula that are broad in scope has the
      potential to change the attitudes of future clinicians toward efforts to control
      costs, collaborate with other health professions, and influence health policies.

PMID- 16565194
TI  - Preparing medical students to care for older adults: the impact of a Senior
      Mentor Program.
AB  - PURPOSE: To provide alternative training experiences for medical students to
      improve the competencies needed to provide care for older adults. METHOD: Part of
      a comprehensive approach to integrating geriatric content at the University of
      South Carolina (USC) School of Medicine, the Senior Mentor Program (SMP) was
      launched in 2000. The SMP links pairs of students with older community volunteers
      in the spring of the first year. Students visit their mentors throughout medical
      school, and execute assignments that complement materials covered in the
      traditional curriculum. To evaluate the feasibility and efficacy of the SMP, the
      authors describe the program's operation and outputs, the extent to which
      undergraduate medical education at USC and the SMP meet the core competencies for
      care of older adults promulgated by the American Geriatrics Society (AGS), and
      analyze the coverage of geriatrics content from 2000 to 2005 at USC, as indicated
      by responses to the Medical School Graduation Questionnaire. RESULTS: From 2000
      to 2005, 379 students enrolled in the SMP; 133 graduates of the classes of 2004
      and 2005 have completed the SMP. Students and mentors indicated high acceptance
      and enthusiasm. The program has been maintained with minimal administrative
      burden. USC covered only half of AGS competencies before the SMP, but now covers
      100%, with nearly a third met specifically through the SMP. USC graduates
      reporting inclusion of geriatrics throughout their four years of training rose
      from 66% in 2002 to 96% in 2004-05. CONCLUSIONS: The SMP has had a substantial
      impact on students' preparation for dealing with an aging patient population.

PMID- 16565196
TI  - A model for improving physician performance in developing countries: a three-year
      postgraduate training program in Laos.
AB  - The Faculty of Medical Sciences of the National University of Laos, in
      partnership with Health Frontiers, an American nonprofit organization, Case
      Western Reserve University of Cleveland, Ohio, and Khon Kaen University of Khon
      Kaen, Thailand, administer a postgraduate internal medicine training program for
      Lao physicians. Begun in 2001, the program admits six participants per year;
      participants complete clinical rotations in three hospitals in Vientiane, Laos,
      as well as one other clinical site. The goal of the program is to prepare a core
      group of local physicians to deliver healthcare, and train others according to an
      international standard of care. The program has two exceptional features. First,
      the vast majority of the training takes place in Laos. This avoids the "brain
      drain" that can occur when nationals of developing countries train abroad. In
      addition, because the training uses personnel, facilities, and technology
      available locally, graduates are better prepared to serve the needs of the Lao
      people. Second, the partnership is an all-volunteer model, committed to a long
      term undertaking. American-trained specialists who live in Laos are available to
      work with the participants on a daily basis. Participants have a long period of
      time to acquire, reinforce, and be tested in new knowledge and benefit from
      learning from American colleagues who model an evidence-based approach to medical
      care, while still working in local conditions. As more Lao physicians receive
      this level of training, the program will become locally sustainable and help
      break a cycle of dependency on foreign expertise within the Lao health care
      sector. Preliminary results suggest that the program is succeeding, and could be
      replicated elsewhere.

PMID- 16565197
TI  - Giving learners the best of both worlds: do clinical teachers need to guard
      against teaching pattern recognition to novices?
AB  - PURPOSE: There has been much debate in the medical education literature regarding
      the extent to which feature-driven and nonanalytic (similarity-based) reasoning
      strategies define expertise, but the relative value of teaching these strategies,
      together or in isolation, remains uncertain. The purpose of this study was to
      compare the diagnostic accuracy achieved upon receiving instruction to use each
      strategy in isolation to that of a combined approach. METHOD: In 2003-04, 48
      undergraduate psychology students from McMaster University in Ontario, Canada,
      were taught to diagnose ten cardiac disorders (including normal) via
      electrocardiogram (ECG) presentation. Twelve students were instructed to
      carefully identify all features present before assigning a diagnosis (feature
      first). Twelve were given the same instruction with notice that some test ECGs
      had been seen during training (implicit combined). Twelve were simply instructed
      to trust familiarity and diagnose based on this impression (similarity-based).
      Finally, 12 students were given feature first and similarity-based instructions
      in combination (explicit combined). RESULTS: No difference in diagnostic accuracy
      was observed between the groups given the feature first (42%) and first
      impression (41%) instructions (p > .4), but the groups instructed to use both
      strategies (explicitly or implicitly) performed significantly better (56% and
      53%, respectively; p < .01). CONCLUSIONS: The results support an additive model
      of clinical reasoning in which instructions to be feature oriented and to trust
      similarity improve performance in novice diagnosticians.

PMID- 16565198
TI  - The calculation of SAR from limb current in the female voxel phantom, NAOMI.
AB  - Calculations of localised SAR in the legs and arms have been performed in a
      female voxel phantom, NAOMI. A finite difference method was used to solve the
      quasistatic potential equation from 0.1 to 80 MHz for a unit current injected
      into a limb. The relationship between limb current and SAR has been investigated.
      The values of localised SAR in the leg as a function of applied plane wave
      electric field are also predicted from the knowledge of limb currents calculated
      by the finite-difference time-domain (FDTD) method for whole-body exposure.
      Comparisons are made with the results of previous work for the normalised male
      model, NORMAN, and the implications for electromagnetic guidelines are discussed.

PMID- 16565199
TI  - Natural radioactivity and evaluation of effective dose equivalent of granites in
      Turkey.
AB  - Annual effective dose equivalent due to natural gamma radiation from (238)U,
      (232)Th and (40)K have been evaluated from granites in Turkey. Forty samples were
      taken for spectrometric analysis. Specific concentrations of (238)U, (232)Th and
      (40)K in granite samples were determined. Spectroscopy system was used with 1.8
      keV (FWHM) coaxial high purity germanium (HPGe) detector. Average values of
      concentrations of (238)U, (232)Th and (40)K were detected at 15.85, 33.76 and 359
      Bq kg(-1), respectively. The average value of radon varies from 0.073 to 0.185 Bq
      m(-2) h(-1) exhalation depends on the specific concentration of uranium. The dose
      rate due to this highest activity which have been evaluated by a Monte Carlo
      transport calculations does not exceed 0.4 mSv a(-1).

PMID- 16565200
TI  - Optical bleaching, TSL and OSL features of CVD diamond.
AB  - Luminescence and optical features of chemical vapour deposition (CVD) diamond
      have been studied in view of the potential application of this material in
      ionising radiation dosimetry field. For this purpose, thermally stimulated
      luminescence (TSL) and optically stimulated luminescence (OSL) techniques have
      been used. A large amount of work has emphasised the excellent dosimetric
      properties of CVD diamond. Nevertheless, TSL measurements showed that after
      irradiation, this material is extremely sensitive to ambient light and the stored
      dose information is drastically affected by optical bleaching. From OSL analysis,
      it follows that both types of processes (TSL and OSL) were characterised by the
      same excitation and emission spectra and that optical bleaching originated from a
      broad stimulation band lying from visible to near infrared with a continuous
      character.

PMID- 16565201
TI  - Thermoluminescence properties of CVD diamond for clinical dosimetry use.
AB  - The application of diamond to dosimetry is desirable because of its tissue
      equivalence, chemical inertness and small size, but this has not been
      commercially viable owing to the non-reproducible response of natural diamond.
      The chemical vapour deposition (CVD) of diamond permits controlled, reproducible
      and large-scale production of this material at potentially low cost. An
      investigation of some clinically relevant features like the depth-dose
      distribution as well as the absorbed dose profile, obtained using
      thermoluminescence (TL), is reported for several CVD diamond films. The TL
      characterisation presented here shows that CVD diamond films should be excellent
      TL-mode detectors in instances of radiotherapy and in vivo radiation dosimetry.

PMID- 16565202
TI  - Neutron scattering in concrete and wood.
AB  - In this work, the energy spectra of photoneutrons, scattered by ordinary, high
      density concrete and wood barriers, have been evaluated using the MCNP4B code.
      These spectra were calculated for different scattering angles, and for incident
      neutron energies varying between 0.1 and 10 MeV. The results presented are
      required to simulate typical photoneutron fluence, produced by medical
      accelerators, which is scattered by the room walls and reaches the door. It was
      found that the mean energy of the scattered neutrons does not depend on the
      scattering angle. Furthermore, it was found that the scattered neutron energies
      are lower in wood and baryte concrete, which indicates that these materials can
      be used for lining the maze walls in order to reduce neutron dose at the room
      door. These data will help to estimate the personal dose received by the patient
      and staff in radiotherapy facilities.

PMID- 16565203
TI  - Self-indicating radiation alert dosemeter (SIRAD).
AB  - In an event of a nuclear or dirty bomb explosion and a radiological accident,
      there is a need for self-indicating instant radiation dosemeter for monitoring
      radiation exposure. The self-indicating instant radiation alert dosemeter (SIRAD)
      is a credit card size radiation dosemeter for monitoring ionising radiation from
      a few hundredths of a Gray to a few Gray. It is always active and is ready to
      use. It needs no battery. The dosemeter develops colour instantly upon exposure,
      and the colour intensifies with dose. It has a colour chart so that the dose on
      the active element may be read by matching its colour with the chart that is
      printed next to it on the card. However, in this work, the dose is measured by
      the optical density of the element. The dosemeter cannot be reset. The response
      changes by <1% per degrees C from -20 to +60 degrees C. The shelf-life is >3 y at
      room temperature. It contains no hazardous materials. The dosemeter would meet
      the requirements of instantly monitoring high dose in an event of a nuclear or
      dirty bomb explosion or a radiation accident.

PMID- 16565204
TI  - LET and dose dependence of TLD-100 glow curve after exposure to intermediate
      energy ions.
AB  - We present results from measurements performed with low fluences (10(5)-10(6) cm(
      2)) of 15, 25 and 40 MeV u(-1) carbon, 25 MeV u(-1) oxygen and 40 MeV u(-1) neon
      ions incident on TLD-100 chips. Dosemeters were arranged individually or in
      stacks in front of the beam, allowing the study of various linear energy transfer
      (LET) values simultaneously. The thermoluminescence (TL) total signal is observed
      to be a linear function of deposited energy. To assess the contribution to the
      glow curve from the high-temperature peaks, two methods were studied: ratios of
      peak heights (peak 7 with respect to peak 5), and ratios of areas of the
      deconvoluted high-temperature peaks with respect to peak 5. The ratios were
      evaluated as a function of dose, showing in both methods a dependence on LET and
      ion identity. Some of the studied ions show these ratios to be independent of
      dose, up to 500 mGy, while for other ions, departures from linearity up to 4.5%
      +/- 2.5% per 100 mGy are observed at 500 mGy. These results show that, in
      general, the incident radiation LET is not a parameter that can be deduced from
      the glow curve.

PMID- 16565205
TI  - Barium dithionate as an EPR dosemeter.
AB  - Electron paramagnetic resonance (EPR) dosimetry is growing in popularity and this
      success has encouraged the search for other dosimetric materials. Previous
      studies of gamma-irradiated barium dithionate (BaS(2)O(6) x 2H(2)O) have shown
      promise for its use as a radiation dosemeter. This work studies in greater detail
      several essential attributes of the system. Special attention has been directed
      to the study of EPR response dependences on microwave power, irradiation
      temperature, minimum detectable dose and post-irradiation stability.

PMID- 16565206
TI  - EPR/alanine dosimetry in LDR brachytherapy--a feasibility study.
AB  - In this study, we present the results of in vivo dosimetry, using electron
      paramagnetic resonance in l-alanine, performed on 13 patients treated for
      gynaecological cancers. The doses from (137)Cs (12 samples) and (192)Ir (one
      sample) brachytherapy sources were determined inside vagina. The detectors had a
      form of small cellulose capsules tightly filled with crystalline alanine. The
      positions of the detectors were reconstructed from two orthogonal radiographs.
      The planned doses were calculated with a computer planning system (PLATO,
      Nucletron). The relative deviations between planned and measured doses ranged
      from -23 to +14%. The mean deviation from the prescribed dose was relatively low
      (-5%) with SD of 10%. The main sources of differences between the measured and
      calculated doses were attributed to uncertainty in the determination of the
      detector position inside the patient's body and to uncontrolled changes in the
      detector position during the treatment.

PMID- 16565207
TI  - Progress towards a polymineral single-aliquot OSL dating procedure.
AB  - Published single-aliquot regenerative-dose (SAR) procedures for quartz use a
      'cutheat' different from the pre-heat. In contrast, previous work has shown that
      the SAR procedure can be used to correct for sensitivity changes exhibited by
      feldspars if the cutheat is equal to the pre-heat. In this paper, a procedure
      that corrects for sensitivity changes in both quartz and feldspar is tested. The
      results indicate that for sedimentary quartz the cutheat can be equal to the pre
      heat. Thus, it may be possible to develop one procedure to measure equivalent
      doses in a polymineral sample. We also tested several different optical
      stimulation methods. Using the infrared (IR)-stimulated signal from a post-IR
      blue-stimulated optically stimulated luminescence sequence extends the potential
      age range when using feldpathic materials. In addition, since the post-IR blue
      stimulated signal from feldspar is much smaller than the blue-stimulated signal
      from quartz, the possibility exists of extracting a 'quartz signal' from a mixed
      mineral sample.

PMID- 16565208
TI  - Combined effects of high doses and temperature on radiation-induced radicals and
      their relative contributions to EPR signal in gamma-irradiated alanine.
AB  - Electron Paramagnetic Resonance (EPR) study of irradiated l-alanine showed
      differences in dose-response curves obtained at low and high microwave power for
      a broad range of doses, up to 3000 kGy. A mathematical model was fitted to
      experimental data and calculated yields of generation and of destruction of
      radicals showed variations with microwave power. The calculations were applied to
      both double integrals of the total EPR signal and to its components reflecting
      contributions of radicals R1, R2 and R3 in the alanine EPR signal. The relative
      contributions of radicals R1, R2 and R3 varied with dose >100 kGy; an increase in
      relative contribution of R3 was accompanied by a decrease in contribution of R1
      radicals. The observed fading of EPR signal intensity in samples annealed to 175
      208 degrees C was a strong function of dose, and varied by 2-3 orders of
      magnitude in the dose range examined.

PMID- 16565209
TI  - Luminescence dating of the barrier spit at Chilika Lake, Orissa, India.
AB  - Optically stimulated luminescence dating has been used to investigate the
      chronological development of the outer barrier spit forming Chilika Lake (Orissa,
      India), the largest brackish-water lagoon in Asia. Sixteen samples were examined,
      and these yielded equivalent doses of between 153 +/- 3 mGy and 2.23 +/- 0.07 Gy,
      corresponding to ages from approximately 40 y at the top of the spit to
      approximately 300 y at the bottom. The youngest ages are consistent with the age
      of the overlying vegetation, and modern material taken from the sub-tidal beach
      gave a dose of 4 +/- 2 mGy (corresponding to an age of 0.7 +/- 0.4 y), confirming
      that any previous potential luminescence signal in the source sediment is
      completely set to zero before incorporation into the spit. A clearly defined
      period of >2.5 m of barrier construction approximately 40 y ago is identified;
      prior to that the deposition rate was relatively constant for approximately 300
      y.

PMID- 16565210
TI  - Highly active antiretroviral therapy (HAART) improves survival in HIV-associated
      Hodgkin's disease: results of a multicenter study.
AB  - BACKGROUND: The purpose of the study was to evaluate the outcome of Hodgkin's
      disease (HD) in patients infected with the human immunodeficiency virus (HIV)
      with respect to the use of highly active antiretroviral therapy (HAART).
      MATERIALS AND METHODS: This cohort study included patients with HIV-HD diagnosed
      from June 1984 to February 2004. Patients treated in the pre-HAART era (1984
      1996) were compared with those belonging to the HAART era (1997-2004). RESULTS:
      Of 66 patients with HIV-HD, 47 (71%) presented with stage III/IV disease and 38
      patients (58%) with an AIDS-defining illness. Fifty-nine of 66 patients (89.4%)
      underwent curative intended chemotherapy. Patients receiving HAART (n = 34) had a
      significantly better 2-year overall survival (OS) than those not receiving HAART
      (74% versus 30%, P <0.001). The 2-year OS of HAART-responders was 88% compared
      with 19% in patients without HAART-response (P = 0.0002). By multivariate
      analysis patients without HAART had a 5.6-fold higher risk for 3-year mortality
      [HR 5.6, 95% confidence interval (CI) 2.20-14.26]. Three-year mortality was
      significantly higher in patients without complete remission (HR 4.40, CI 1.77
      10.99), with stage III/IV HD (HR 4.64, CI 1.31-16.49) and with CD4 cells
      <200/microl (HR 2.69, CI 0.99-7.33). CONCLUSIONS: Use of HAART significantly
      improved the overall survival in patients with HIV-HD.

PMID- 16565211
TI  - A good death for cancer patients: still a dream?

PMID- 16565212
TI  - Temozolomide in metastatic breast cancer (MBC): a phase II trial of the National
      Cancer Institute of Canada - Clinical Trials Group (NCIC-CTG).
AB  - BACKGROUND: Temozolomide is an oral alkylating agent that crosses the blood-brain
      barrier, and has preclinical activity in breast cancer. This phase II trial
      sought to determine the activity and toxicity of temozolomide in metastatic
      breast cancer (MBC). Temozolomide was administered in a dose dense schedule of
      150 mg/m(2) on days 1-7 and 15-21 in a 28-day cycle. MATERIALS AND METHODS:
      Patients had unidimensional disease for response assessment by RECIST criteria,
      up to two prior chemotherapy regimens for MBC, and may have had brain metastases
      if radiation was not expected to be required within 4 weeks. RESULTS: Nineteen
      women were entered on the study. All were evaluable for toxicity and 18 were
      evaluable for response. The median age was 54 years; 14 had prior chemotherapy
      for MBC and 12 had prior hormones. Sites of disease included bone, brain, liver
      and lung. Treatment was well tolerated with 14/19 receiving >90% planned dose
      intensity. Common grade 1-3 drug-related effects included nausea, fatigue,
      vomiting, anorexia and skin rash. Grade 3-4 hematologic toxicities included
      granulocytopenia and thrombocytopenia. Of the 18 evaluable patients, there were
      no objective responses; three had stable disease and 15 progressive disease.
      CONCLUSIONS: No responses to temozolomide were documented in these heavily
      pretreated women with extensive MBC including brain metastases.

PMID- 16565213
TI  - Merkel cell cancer of the skin.
AB  - Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumor of the elderly
      with rapidly growing skin nodules found predominantly on sun-exposed areas of the
      body. The vast majority of patients present with localized disease, while up to
      30% have regional lymph node metastases. Despite local excision and the incidence
      of local recurrence, regional lymph node metastases and distant metastases is
      high and usually occurs within 2 years of primary diagnosis. The optimal
      treatment for patients with MCC remains unclear. The best outcome is achieved
      with multidisciplinary management including surgical excision of primary tumor
      with adequate margins and post-operative radiotherapy (RT) to control local and
      regional disease. Patients with regional nodal metastases should be treated with
      lymph node dissection plus RT. Adjuvant chemotherapy (CT) should be considered as
      part of the initial management. In case of metastatic disease CT based on
      regimens used for small-cell lung cancer is the standard treatment of care.

PMID- 16565214
TI  - Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in
      Catharanthus roseus cells.
AB  - Rational engineering of complicated metabolic networks involved in the production
      of biologically active plant compounds has been greatly impeded by our poor
      understanding of the regulatory and metabolic pathways underlying the
      biosynthesis of these compounds. Whereas comprehensive genome-wide functional
      genomics approaches can be successfully applied to analyze a select number of
      model plants, these holistic approaches are not yet available for the study of
      nonmodel plants that include most, if not all, medicinal plants. We report here a
      comprehensive profiling analysis of the Madagascar periwinkle (Catharanthus
      roseus), a source of the anticancer drugs vinblastine and vincristine. Genome
      wide transcript profiling by cDNA-amplified fragment-length polymorphism combined
      with metabolic profiling of elicited C. roseus cell cultures yielded a collection
      of known and previously undescribed transcript tags and metabolites associated
      with terpenoid indole alkaloids. Previously undescribed gene-to-gene and gene-to
      metabolite networks were drawn up by searching for correlations between the
      expression profiles of 417 gene tags and the accumulation profiles of 178
      metabolite peaks. These networks revealed that the different branches of
      terpenoid indole alkaloid biosynthesis and various other metabolic pathways are
      subject to differing hormonal regulation. These networks also served to identify
      a select number of genes and metabolites likely to be involved in the
      biosynthesis of terpenoid indole alkaloids. This study provides the basis for a
      better understanding of periwinkle secondary metabolism and increases the
      practical potential of metabolic engineering of this important medicinal plant.

PMID- 16565215
TI  - Mitochondria as signaling organelles in the vascular endothelium.
AB  - Vascular endothelial cells are highly glycolytic and consume relatively low
      amounts of oxygen (O(2)) compared with other cells. We have confirmed that
      oxidative phosphorylation is not the main source of ATP generation in these
      cells. We also show that at a low O(2) concentration (<1%) endogenous NO plays a
      key role in preventing the accumulation of the alpha-subunit of hypoxia-inducible
      factor 1. At higher O(2) concentrations (1-3%) NO facilitates the production of
      mitochondrial reactive oxygen species. This production activates the AMP
      activated protein kinase by a mechanism independent of nucleotide concentrations.
      Thus, the primary role of mitochondria in vascular endothelial cells may not be
      to generate ATP but, under the control of NO, to act as signaling organelles
      using either O(2) or O(2)-derived species as signaling molecules. Diversion of
      O(2) away from endothelial cell mitochondria by NO might also facilitate
      oxygenation of vascular smooth muscle cells.

PMID- 16565216
TI  - Cytoplasmic gamma-actin contributes to a compensatory remodeling response in
      dystrophin-deficient muscle.
AB  - Dystrophin mechanically links the costameric cytoskeleton and sarcolemma, yet
      dystrophin-deficient muscle exhibits abnormalities in cell signaling, gene
      expression, and contractile function that are not clearly understood. We
      generated new antibodies specific for cytoplasmic gamma-actin and confirmed that
      gamma-actin most predominantly localized to the sarcolemma and in a faint
      reticular lattice within normal muscle cells. However, we observed that gamma
      actin levels were increased 10-fold at the sarcolemma and within the cytoplasm of
      striated muscle cells from dystrophin-deficient mdx mice. Transgenic
      overexpression of the dystrophin homologue utrophin, or functional dystrophin
      constructs in mdx muscle, restored gamma-actin to normal levels, whereas gamma
      actin remained elevated in mdx muscle expressing nonfunctional dystrophin
      constructs. We conclude that increased cytoplasmic gamma-actin in dystrophin
      deficient muscle may be a compensatory response to fortify the weakened
      costameric lattice through recruitment of parallel mechanical linkages. However,
      the presence of excessive myoplasmic gamma-actin may also contribute to altered
      cell signaling or gene expression in dystrophin-deficient muscle.

PMID- 16565217
TI  - Neuronal metabolism governs cortical network response state.
AB  - The level of arousal in mammals is correlated with metabolic state and specific
      patterns of cortical neuronal responsivity. In particular, rhythmic transitions
      between periods of high activity (up phases) and low activity (down phases) vary
      between wakefulness and deep sleep/anesthesia. Current opinion about changes in
      cortical response state between sleep and wakefulness is split between neuronal
      network-mediated mechanisms and neuronal metabolism-related mechanisms. Here, we
      demonstrate that slow oscillations in network state are a consequence of
      interactions between both mechanisms. Specifically, recurrent networks of
      excitatory neurons, whose membrane potential is partly governed by ATP-modulated
      potassium (K(ATP)) channels, mediate response-state oscillations via the
      interaction between excitatory network activity involving slow, kainate receptor
      mediated events and the resulting activation of ATP-dependent homeostatic
      mechanisms. These findings suggest that K(ATP) channels function as an interface
      between neuronal metabolic state and network responsivity in mammalian cortex.

PMID- 16565218
TI  - Costs and benefits of priming for defense in Arabidopsis.
AB  - Induced resistance protects plants against a wide spectrum of diseases; however,
      it can also entail costs due to the allocation of resources or toxicity of
      defensive products. The cellular defense responses involved in induced resistance
      are either activated directly or primed for augmented expression upon pathogen
      attack. Priming for defense may combine the advantages of enhanced disease
      protection and low costs. In this study, we have compared the costs and benefits
      of priming to those of induced direct defense in Arabidopsis. In the absence of
      pathogen infection, chemical priming by low doses of beta-aminobutyric acid
      caused minor reductions in relative growth rate and had no effect on seed
      production, whereas induction of direct defense by high doses of beta
      aminobutyric acid or benzothiadiazole strongly affected both fitness parameters.
      These costs were defense-related, because the salicylic acid-insensitive defense
      mutant npr1-1 remained unaffected by these treatments. Furthermore, the
      constitutive priming mutant edr1-1 displayed only slightly lower levels of
      fitness than wild-type plants and performed considerably better than the
      constitutively activated defense mutant cpr1-1. Hence, priming involves less
      fitness costs than induced direct defense. Upon infection by Pseudomonas syringae
      or Hyaloperonospora parasitica, priming conferred levels of disease protection
      that almost equaled the protection in benzothiadiazole-treated wild-type plants
      and cpr1 plants. Under these conditions, primed plants displayed significantly
      higher levels of fitness than noninduced plants and plants expressing chemically
      or cpr1-induced direct defense. Collectively, our results indicate that the
      benefits of priming-mediated resistance outweigh the costs in environments in
      which disease occurs.

PMID- 16565219
TI  - Controlling methicillin-resistant Staphylococcus aureus: quantifying the effects
      of interventions and rapid diagnostic testing.
AB  - Control of nosocomial transmission of methicillin-resistant Staphylococcus aureus
      (MRSA) has been unsuccessful in most countries. Yet, some countries have
      maintained low endemic levels by implementing nationwide MRSA-specific infection
      control measures, such as "search & destroy" (S&D). These strategies, however,
      are not based on well designed studies, and their use in countries with high
      levels of endemicity is controversial. We present a stochastic three-hospital
      model and an analytical one-hospital model to quantify the effectiveness of
      different infection control measures and to predict the effects of rapid
      diagnostic testing (RDT) on isolation needs. Isolation of MRSA carriers
      identified by clinical cultures is insufficient to control MRSA. However,
      combined with proactive search (of high-risk patients on admission and/or
      contacts of index patients), it will maintain prevalence levels <1%. Concerted
      implementation of S&D in countries with high nosocomial endemicity reduces
      nosocomial prevalence to <1% within 6 years. Stepwise implementation of control
      measures can reduce isolation capacities needed. RDT can reduce isolation needs
      by >90% in low-endemic settings and by 20% in high-endemic settings. Surveillance
      of colonization and improved hand hygiene can markedly increase control efficacy.
      These findings strongly suggest that: (i) causality exists between S&D and low
      MRSA prevalence; (ii) isolating MRSA carriers identified by clinical cultures as
      a single measure is insufficient for control; (iii) a combined approach of
      isolation and screening confers efficacy; and (iv) MRSA-prevalence levels can be
      reduced to <1% in high-endemic settings by S&D or a stepwise approach to
      interventions. RDT can markedly enhance feasibility.

PMID- 16565220
TI  - Phosphoproteome analysis of the human mitotic spindle.
AB  - During cell division, the mitotic spindle segregates the sister chromatids into
      two nascent cells, such that each daughter cell inherits one complete set of
      chromosomes. Errors in spindle formation can result in both chromosome
      missegregation and cytokinesis defects and hence lead to genomic instability. To
      ensure the correct function of the spindle, the activity and localization of
      spindle associated proteins has to be tightly regulated in time and space.
      Reversible phosphorylation has been shown to be one of the key regulatory
      mechanisms for the organization of the mitotic spindle. The relatively low number
      of identified in vivo phosphorylation sites of spindle components, however, has
      hampered functional analysis of regulatory spindle networks. A more complete
      inventory of the phosphorylation sites of spindle-associated proteins would
      therefore constitute an important advance. Here, we describe the mass
      spectrometry-based identification of in vivo phosphorylation sites from purified
      human mitotic spindles. In total, 736 phosphorylation sites were identified, of
      which 312 could be attributed to known spindle proteins. Among these are
      phosphorylation sites that were previously shown to be important for the
      regulation of spindle-associated proteins. Importantly, this data set also
      comprises 279 novel phosphorylation sites of known spindle proteins for future
      functional studies. This inventory of spindle phosphorylation sites should thus
      make an important contribution to a better understanding of the molecular
      mechanisms that regulate the formation, function, and integrity of the mitotic
      spindle.

PMID- 16565221
TI  - Potential role of leptin expression in hepatocellular carcinoma.
AB  - BACKGROUND: Obesity is associated with hepatocellular carcinoma (HCC). The
      association may result from the aberrant expression of adipokines. AIM: To
      explore the potential biological effect and prognostic value of leptin, one of
      the adipokines, in HCC. METHODS: Immunohistochemistry was used to evaluate the
      expression of leptin in 68 patients with HCC. The expression of Ki-67 and
      microvessel density (MVD) of tumorous lesions in HCC were also analysed. The
      result of leptin expression was further correlated with Ki-67 expression,
      intratumour MVD, clinicopathological characteristics, overall survival and the
      postoperative use of medroxyprogesterone acetate (MPA). RESULTS: High leptin
      expression was seen in 60.3% of patients with HCC and was significantly
      correlated with intratumour MVD (high v low; 59.2 (standard deviation 3.2) v 44.2
      (19.5), p = 0.004), but not with Ki-67 expression. No marked correlation was seen
      between leptin expression and clinicopathological characteristics. However, using
      a multivariate Cox's proportional hazards model, leptin expression was a
      predictor for improved overall survival of patients with HCC (odds ratio 0.16;
      95% confidence interval 0.03 to 0.87; p = 0.033). In addition, the Kaplan-Meier
      survival curve showed that high leptin expression was associated with a better
      survival in patients with HCC, treated postoperatively with MPA (p = 0.008, log
      rank test). CONCLUSION: High leptin expression was associated with an increased
      intratumour MVD and thus may be associated with HCC development. In addition,
      high leptin expression was a predictor for improved survival of patients with
      HCC, treated postoperatively with MPA.

PMID- 16565222
TI  - Limitations in the ability of NB84 to detect metastatic neuroblastoma cells in
      bone marrow.
AB  - BACKGROUND: The accurate assessment of metastases is an essential component of
      the staging process for children with neuroblastoma. AIMS: To study the
      sensitivity of the immunohistochemical marker neuroblastoma 84 (NB84) for the
      detection of bone marrow infiltrates in children with stage 4 neuroblastoma.
      METHODS: Primary tumour specimens, bone marrow trephine biopsy specimens and
      lymph node metastases, taken from children with neuroblastoma that had
      metastasised to bone marrow, were assessed with a panel of commonly used
      immunohistochemical markers for neuroblastoma. A comparison was drawn between the
      sensitivity of the marker NB84 for primary tumours and for bone marrow
      metastases. RESULTS: NB84 immunolabelled all pre-chemotherapy and post
      chemotherapy (n = 24) paired primary tumour specimens, as well as each of a
      further 20, unpaired, pre-chemotherapy primary tumour specimens. It also labelled
      all (n = 4) lymph node metastases. Immunolabelling of bone marrow trephine biopsy
      specimens (21/33) was less sensitive. Of 16 primary tumour specimens with a
      paired bone marrow trephine biopsy specimen, all immunostained positive, whereas
      only 62.5% of bone marrow biopsy specimens immunostained positive for NB84. The
      number of bone marrow biopsy specimens immunostaining for NB84 was significantly
      lower than the number of paired primary tumour specimens (p = 0.041).
      CONCLUSIONS: NB84 remains a useful marker for the diagnosis of neuroblastoma in
      primary tumour specimens, but not for neuroblastoma that has metastasised to bone
      marrow.

PMID- 16565223
TI  - Methylation of INK4 and CIP/KIP families of cyclin-dependent kinase inhibitor in
      chronic lymphocytic leukaemia in Chinese patients.
AB  - BACKGROUND: INK4 (p15, p16, p18 and p19) and CIP/KIP (p21, p27 and p57) are two
      families of cyclin-dependent kinase inhibitors (CKI) targeting CDK4/6 and CDK2,
      respectively. AIM: To study the role of methylation in the inactivation of CKI in
      chronic lymphocytic leukaemia (CLL). MATERIALS AND METHODS: Methylation-specific
      polymerase chain reaction was carried out on DNA obtained from the bone marrow of
      56 newly diagnosed patients with CLL. RESULTS: Similar demographic features and
      clinical outcome were observed in our patients when compared with Caucasian
      patients, including an indolent clinical course (10-year overall survival 51%)
      and advanced Rai stage (p = 0.006), and a high-risk karyotype such as trisomy 12
      and complex aberrations (p = 0.03). In the INK4 family, methylation in p15 and
      p16 occurred in 20 (35.7%) and 8 (14.3%) patients, respectively. In all, 5 (8.9%)
      CLL samples harboured concurrent methylation of both p15 and p16. Apart from an
      association of p16 methylation with higher presenting leucocyte count (64.5 x
      10(9)/l in methylated p16 and 16.0 x 10(9)/l in unmethylated p16 patients; p =
      0.016), there was no association between p15 and p16 methylation and age, sex and
      Rai stage. No difference was observed in the overall survival for patients with
      and without p15 and p16 methylation. By contrast, p18 and Rb were unmethylated in
      all samples. In the CIP/KIP family, apart from infrequent methylation of p57 in 4
      (7.1%) patients, methylation of p21 and p27 was uniformly absent. CONCLUSION: p15
      and, less frequently, p16 of the INK4 family of CKI, instead of the CIP or KIP
      family, were targeted by methylation in CLL. p16 methylation was associated with
      a higher lymphocyte count at presentation. This is the first comprehensive study
      of the epigenetic dysregulation of the INK4 and CIP/KIP families of CKI in
      Chinese patients with CLL.

PMID- 16565224
TI  - Comparison of RANTES expression in Crohn's disease and ulcerative colitis: an aid
      in the differential diagnosis?
AB  - BACKGROUND: RANTES (regulated on activation, normal T cell expressed and
      secreted) expression is increased in inflammatory bowel disease (IBD). RANTES is
      produced at higher levels in granulomatous conditions, so increased RANTES
      expression can be expected in Crohn's disease compared with ulcerative colitis.
      AIM: To compare RANTES expression between intestinal biopsy specimens of patients
      with Crohn's disease and those with ulcerative colitis. MATERIALS AND METHODS: A
      prospective study of patients presenting with lower gastrointestinal symptoms at
      the Bahrain Specialist Hospital from July 2004 to April 2005 was carried out.
      Endoscopic colonic biopsy specimens were taken from every patient and subjected
      to (a) routine haematoxylin and eosin staining examination by light microscopy,
      (b) immunohistochemistry for examination of RANTES protein expression by light
      microscopy and (c) in situ hybridisation for examination of RANTES mRNA
      expression by light microscopy. RANTES expression was assessed and quantified.
      RESULTS: 58 patients were enrolled to the study. Of them, 40 had IBD (21 had
      Crohn's disease and 19 had ulcerative colitis), 15 were controls with normal
      colonic biopsy results or non-inflammatory lesions and 3 had colonic inflammatory
      lesions other than IBD. RANTES expression in lymphocytes or histiocytes was
      significantly higher (p = 0.04) in new patients with ulcerative colitis than in
      those with Crohn's disease analysed by immunohistochemistry (IHC). CONCLUSION:
      RANTES expression in lymphocytes or histiocytes is significantly higher in
      patients with ulcerative colitis than in those with Crohn's disease. Hence,
      RANTES IHC can be an effective method for distinguishing between biopsy specimens
      of patients with ulcerative colitis from those of patients with Crohn's disease,
      where routine histological features are indeterminate. RANTES IHC may prove to be
      a useful technique for identifying early or equivocal granulomas.

PMID- 16565225
TI  - Prognostic relevance of P-cadherin expression in melanocytic skin tumours
      analysed by high-throughput tissue microarrays.
AB  - AIM: To investigate whether protein expression or cellular localisation of P
      cadherin is associated with clinicopathological characteristics in benign and
      malignant melanocytic skin tumours. EXPERIMENTAL DESIGN: P-cadherin expression
      and the Ki-67 labelling index were analysed immunohistochemically by using tissue
      microarrays (TMAs). Membranous and cytoplasmic expression was scored
      semiquantitatively (0 to 2+). RESULTS: P-cadherin protein expression of any
      intensity (1+ to 2+) was detected in the membrane in 41.5% (132/318) and in the
      cytoplasm in 64.2% (204/318) of patients. In general, P-cadherin expression was
      significantly reduced in malignant melanomas (p<0.001) and melanoma metastases
      (p<0.001), compared with benign nevi. Additionally, loss of membranous P-cadherin
      was associated with Clark level (p = 0.011) and tumour thickness (p<0.001).
      Interestingly, a significantly lower P-cadherin expression was shown by dermal
      nevi than by compound and junctional nevi (p = 0.005; p = 0.025). In primary
      melanomas, a Ki-67 labelling index <5% was not associated with P-cadherin protein
      expression, suggesting that loss of P-cadherin expression was not associated with
      proliferation. None of the other clinical and histological factors analysed was
      significantly related to P-cadherin expression. Low cytoplasmic P-cadherin
      expression was associated with tumour recurrence (p = 0.03) in all the patients
      who were analysed. After testing various multivariate Cox regression models, loss
      of cytoplasmic P-cadherin expression remained a highly significant adverse risk
      factor for tumour recurrence in patients with tumours <2 mm. CONCLUSIONS: Loss of
      cytoplasmic P-cadherin expression is common in advanced melanomas and can be a
      prognostic marker of progression in patients with melanoma, most useful in
      patients with primary tumours <2 mm in thickness.

PMID- 16565226
TI  - Potential prognostic value of leptin receptor in hepatocellular carcinoma.
AB  - BACKGROUND: Obesity is associated with several human malignancies, including
      hepatocellular carcinoma (HCC). This association may result from the deregulated
      expression of adipokines. AIMS: To explore the potential role and the prognostic
      value of leptin receptor (Ob-R) in HCC. METHODS: 66 patients with pathologically
      confirmed HCC were included in this study. Immunohistochemistry was used to
      evaluate the expression of Ob-R, microvessel density (MVD) and Ki-67 index in
      these patients. Eventually, the profiles of Ob-R expression, obtained by a
      semiquantitative scoring system, were further correlated with Ki-67 expression,
      intratumour MVD, clinicopathological characteristics and overall survival.
      RESULTS: High Ob-R expression was seen in 53% of patients with HCC and was
      significantly correlated with intratumour MVD (high v low; 59.4 (3.2) v 44.7
      (3.7); p = 0.004), but not with Ki-67 expression. In addition, Ob-R expression
      was inversely correlated with vascular invasion (p = 0.037), but not with other
      known clinicopathological characteristics. The Kaplan-Meier survival curve showed
      that high Ob-R expression was associated with a better overall survival (p =
      0.027). Meanwhile, multivariate analysis showed that Ob-R expression was a
      significant determinant for HCC (odds ratio 0.02, 95% confidence interval 0.01 to
      0.85; p = 0.041). CONCLUSION: Ob-R expression may have a potential role in the
      carcinogenesis of HCC. The positive association of Ob-R expression in the
      cancerous lesions of HCC with the survival outcome can be explained by its
      inverse correlation with vascular invasion, and may have prognostic value in HCC.

PMID- 16565227
TI  - Reflex pupillary dilatation in response to skin incision and alfentanil in
      children anaesthetized with sevoflurane: a more sensitive measure of noxious
      stimulation than the commonly used variables.
AB  - BACKGROUND: Estimation of analgesia in anaesthetized children is often imprecise,
      and consequently, anaesthesiologists commonly evaluate children's response to
      surgical stimulation by movement or haemodynamic changes. In adults reflex
      pupillary dilatation has been demonstrated to be a very sensitive measure of
      noxious stimulation, correlated with opioid concentrations. The autonomic nervous
      control changes with age, raising the hypothesis that mechanisms involved in
      pupillary autonomic functions regarding both sympathetic and parasympathetic
      components may also differ between adults and children. In this pilot study, we
      tested the hypothesis that the pupillary reflex dilatation might allow assessment
      of noxious stimulation and analgesic effect of alfentanil in children under
      sevoflurane anaesthesia, as an alternative to haemodynamic and bispectral
      measures. METHODS: After sevoflurane induction, 24 children were maintained in
      steady-state conditions at 1.5 MAC of sevoflurane in O(2)-N(2)O (50-50). An
      intense noxious stimulation was provided by standardized skin incision on the
      lower limb. A bolus of alfentanil (10 microg kg(-1)) was administered either 1
      min (n=16) or 2 min (n=8) after skin incision. Haemodynamic values, bispectral
      index (BIS) and pupillary diameter (PD) were recorded just before stimulation and
      at 30-60 s intervals during 4 subsequent minutes. RESULTS: In all children PD
      increased significantly after noxious stimulation [+200 (40)%, at 60 s]. In
      contrast, mean heart rate and blood pressure increased only 11 (7)% and 10 (8)%
      respectively, 60 s after stimulation. BIS did not change significantly. In all
      children, alfentanil injection induced a rapid decrease of PD and restored pre
      incision values in 2 min. CONCLUSION: PD is a more sensitive measure of noxious
      stimulation than the commonly used variables of heart rate, arterial blood
      pressure and BIS in children anaesthetized with sevoflurane.

PMID- 16565228
TI  - Perioperative cardiac arrest: a study of 53,718 anaesthetics over 9 yr from a
      Brazilian teaching hospital.
AB  - BACKGROUND: Little information exists regarding factors influencing perioperative
      cardiac arrests and their outcome. This survey evaluated the incidence, causes
      and outcome of perioperative cardiac arrests in a Brazilian tertiary general
      teaching hospital between April 1996 and March 2005. METHODS: The incidence of
      cardiac arrest during anaesthesia was prospectively identified from an
      anaesthesia database. There were 53,718 anaesthetics during the study period.
      Data collected included patient characteristics, surgical procedures (elective,
      urgent or emergency), ASA physical status classification, anaesthesia provider
      information, type of surgery, surgical areas and outcome. All cardiac arrests
      were retrospectively reviewed and grouped by cause of arrest and death into one
      of four groups: totally anaesthesia related, partially anaesthesia related,
      totally surgery related or totally patient disease or condition related. RESULTS:
      One hundred and eighty-six cardiac arrests (34.6:10,000) and 118 deaths
      (21.97:10,000) were found. Major risk factors for cardiac arrest were neonates,
      children under 1 yr and the elderly (P<0.05), male patients with ASA III or
      poorer physical status (P<0.05), in emergency surgery (P<0.05) and under general
      anaesthesia (P<0.05). Patient disease/condition was the major cause of cardiac
      arrest or death (P<0.05). There were 18 anaesthesia-related cardiac arrests
      (3.35:10,000) -- 10 totally attributed (1.86:10,000) and 8 partially related to
      anaesthesia (1.49:10,000). There were 6 anaesthesia-related deaths (1.12:10,000) 
      - 3 totally attributable and 3 partially related to anaesthesia (0.56:10,000 in
      both cases). The main causes of anaesthesia-related cardiac arrest were
      respiratory events (55.5%) and medication-related events (44.5%). CONCLUSIONS:
      Perioperative cardiac arrests were relatively higher in neonates, infants, the
      elderly and in males with severe underlying disease and under emergency surgery.
      All anaesthesia-related cardiac arrests were related to airway management and
      medication administration which is important for prevention strategies.

PMID- 16565229
TI  - A comparison of bispectral index and entropy monitoring, in patients undergoing
      embolization of cerebral artery aneurysms after subarachnoid haemorrhage.
AB  - BACKGROUND: Processed EEG monitoring of anaesthetic depth could be useful in
      patients receiving general anaesthesia following subarachnoid haemorrhage. We
      conducted an observational study comparing performance characteristics of
      bispectral index (BIS) and entropy monitoring systems in these patients. METHODS:
      Thirty-one patients of the World Federation of Neurosurgeons grades 1 and 2,
      undergoing embolization of cerebral artery aneurysms following acute subarachnoid
      haemorrhage, were recruited to have both BIS and entropy monitoring during
      general anaesthesia. BIS and entropy indices were matched to clinical indicators
      of anaesthetic depth. Anaesthetists were blinded to the anaesthetic depth
      monitoring indices. Analysis of data from monitoring devices allowed calculation
      of prediction probability (P(K)) constants, and receiver operating characteristic
      (ROC) analysis to be performed. RESULTS: BIS and entropy [response entropy (RE),
      state entropy (SE)] performed well in their ability to show concordance with
      clinically observed anaesthetic depth. P(K) values were generally high (BIS 0.966
      0.784, RE 0.934-0.663, SE 0.857-0.701) for both forms of monitoring. ROC curve
      analysis shows a high sensitivity and specificity for all monitoring indices when
      used to detect the presence or absence of eyelash reflex. Area under curve for
      BIS, RE and SE to detect the absence or presence of eyelash reflex was 0.932,
      0.888 and 0.887, respectively. RE provides earlier warning of return of eyelash
      reflex than BIS. CONCLUSION: BIS and entropy monitoring perform well in patients
      who receive general anaesthesia after good grade subarachnoid haemorrhage.

PMID- 16565230
TI  - Evaluation of subclinical target organ damage for risk assessment and treatment
      in the hypertensive patients: left ventricular hypertrophy.
AB  - At some point in the natural history of hypertension, the compensatory increase
      in left ventricular mass ceases to be beneficial. Left ventricular hypertrophy
      (LVH) becomes a preclinical disease and an independent risk factor for congestive
      heart failure, ischemic heart disease, arrhythmia, sudden death, and stroke. In
      addition to elevated BP, several mechanisms are involved, including body size,
      age, gender, race, fibrogenic cytokines, and neurohumoral factors, notably
      angiotensin II, which favor interstitial collagen deposition and perivascular
      fibrosis. These tissue changes are responsible for the insidious contractile
      dysfunction that is associated with LVH, consequent to decreased coronary reserve
      and altered diastolic ventricular filling and relaxation. The cardinal
      investigations are echocardiography and electrocardiography. All antihypertensive
      drugs regress LVH, notably those that act on the renin-angiotensin-aldosterone
      system, which also could target the detrimental tissue changes. Regression
      enhances systolic midwall performance, normalizes autonomic function, and
      restores coronary reserve. The resulting improvement in prognosis has enshrined
      the detection, prevention, and reversal of LVH in the current guidelines of
      hypertension management.

PMID- 16565231
TI  - Obesity, arterial stiffness, and cardiovascular risk.
AB  - Long-term follow-up studies have indicated that obesity is an independent
      predictor of cardiovascular risk in both genders. Increased arterial stiffness,
      as reflected by an increased pulse wave velocity, is significantly and
      independently associated with higher risk for cardiovascular morbidity and
      mortality. In recent years, it has been demonstrated that individuals with
      obesity are likely to have an increase in aortic stiffness, independent of BP
      level, ethnicity, and age. The pathophysiologic mechanisms that link abdominal
      adiposity to stiffening are not fully understood. This report focuses on the role
      of arterial stiffness in individuals with obesity and on the association between
      this hemodynamic feature and cardiovascular risk.

PMID- 16565232
TI  - Evaluation of subclinical organ damage for risk assessment and treatment in the
      hypertensive patient: role of microalbuminuria.
AB  - Microalbuminuria, i.e., abnormal urinary excretion of albumin, which is
      detectable by low cost and widely available tests, is a first-line tool for
      identifying hypertensive patients who are at higher cardiovascular (CV) risk.
      Numerous studies have provided evidence that microalbuminuria is a concomitant of
      cardiac and vascular damage as well as a strong, independent predictor of CV
      events. An important, emerging issue is that the risk for CV morbidity and
      mortality is linearly related to urinary albumin excretion and persists well
      below the currently used cutoff for defining microalbuminuria. Furthermore, late
      breaking evidence suggests that a reduction of albuminuria under antihypertensive
      treatment is paralleled by changes in CV risk. The routine search for target
      organ damage by means of microalbuminuria could lead to a significant improvement
      in the evaluation and treatment of patients with primary hypertension.

PMID- 16565233
TI  - The -318 C>G single-nucleotide polymorphism in GNAI2 gene promoter region impairs
      transcriptional activity through specific binding of Sp1 transcription factor and
      is associated with high blood pressure in Caucasians from Italy.
AB  - Inhibiting Galpha subunit 2 protein, which is encoded by the GNAI2 gene, is
      suggested to be pathogenic for essential hypertension and/or insulin resistance.
      The aim of this study was to determine whether GNAI2 variations modulate the risk
      for these abnormalities. Seven single-nucleotide polymorphisms (SNP) at the GNAI2
      locus were identified. Because of either low allelic frequency or unlikely
      biologic relevance (i.e., synonymous or intronic), six SNP were not studied
      further. The -318C>G SNP (allelic frequency 6%) in the promoter region was
      studied for association with adiposity, systolic BP (SBP) and diastolic BP,
      fasting insulin and glucose, and lipids levels in 655 nondiabetic Caucasians from
      Italy. As compared with individuals who carry the C/C genotype, G carriers (i.e.,
      individuals who carry either the G/G or the C/G genotype) had higher SBP (117.8
      +/- 16 versus 113.6 +/- 12.6 mmHg; P = 0.010) and were at increased risk for
      hypertension (odds ratio 2.2; 95% confidence interval 1.1 to 4.5). Compared with
      the C, the G allele had 2.5-fold reduced transcriptional activity in transfected
      HEK293 cells. As predicted by the TRANSFAC database, competition with YY1 or Sp1
      transcription factors specifically reduced the binding of HeLa cell nuclear
      proteins to -318C or -318G allele, respectively, as indicated by shifted
      electrophoretic mobility. A "supershift" of the nuclear proteins/-318G allele
      complex was observed after anti-Sp1 was added but not anti-YY1 antibody. The
      GNAI2 -318 C>G SNP impairs transcriptional activity through specific binding of
      Sp1 and is associated with high SBP in Caucasians from Italy.

PMID- 16565234
TI  - Metabolic syndrome and cardiovascular risk in primary hypertension.
AB  - The metabolic syndrome can be found in approximately one third of patients who do
      not have diabetes but have primary hypertension. Its presence has been associated
      with a wide range of traditional and nontraditional cardiovascular risk factors
      and early signs of cardiovascular and renal damage. Moreover, it was emphasized
      recently that the metabolic syndrome predicts an increased probability of
      sustaining a cardiovascular event or dying. In the clinical setting of insulin
      resistance, attention should be paid to the metabolic side effects of
      antihypertensive drugs; therefore, preference should be given to renin
      angiotensin system inhibitors and calcium channel blockers rather than to beta
      blockers and diuretics.

PMID- 16565235
TI  - Stem cells and the kidney: a new therapeutic tool?
AB  - In the past few years, a number of studies have shown that stem cells can be
      found in virtually every organ of the adult organism. The kidney is not an
      exception, and resident stem cells have been identified both in the papilla and
      along the tubules. Of interest, kidney-bound stem cells have been identified also
      in the bone marrow. When injected, both resident and bone marrow-derived stem
      cells are able to reach the injured renal tissue and, once there, to
      differentiate into renal cells. The evidence that, in humans, some of the acute
      and most of the chronic renal damages lead to ESRD suggests that in normal
      conditions, the reservoir of stem cells (considering both resident and bone
      marrow-derived stem cells) is insufficient to allow a major renal regeneration.
      Probably the number of stem cells that are ready to intervene in an adult kidney
      are sufficient to compensate for the normal cell turnover but largely inadequate
      to counteract a major injury. This is confirmed further by the finding that, even
      by transplanting a syngenic bone marrow in rats with ablation of 5/6 of the renal
      function, it is not possible to increase the life expectancy of the animals.
      Altogether, this evidence suggests that, to clarify the potentiality of a stem
      cell therapy for renal diseases, experiments that aim to clarify the ideal
      concentration of stem cells to be injected and to identify the best way of
      administration are needed.

PMID- 16565236
TI  - Inhibition of diabetic nephropathy in rats by an oral antidiabetic material
      extracted from yeast.
AB  - Diabetic nephropathy is one of the major complications of diabetes. The glucose
      tolerance factor (GTF) is a dietary agent extracted from several natural sources;
      the richest among them is brewer's yeast. Extraction and purification of an
      active and stable GTF preparation from brewer's yeast previously was successful,
      and a remarkable decrease in plasma glucose and lipids from administration of GTF
      to animals with type 1 diabetes was demonstrated. The purpose of the present
      study was to examine whether GTF affects nephropathy in diabetic rats. The
      average urinary volume and protein excretion throughout the collection period in
      diabetic rats was 56.95 +/- 2.2 ml/d and 5.42 +/- 0.95 mg/d, respectively. These
      values were significantly (P < 0.001 versus baseline values) higher compared with
      healthy controls (average urine volume 15.12 +/- 0.5 ml/d; average protein
      excretion 0.15 +/- 0.08 mg/d). Treatment with GTF reduced average urine volume
      and protein excretion to 29.1 +/- 1.94 ml/d (P < 0.01) and 1.55 +/- 1.17 mg/d (P
      < 0.05), respectively. Kidney weight, which was elevated in diabetic rats,
      slightly decreased in diabetic animals that were treated with GTF, in association
      with reduction of lipid peroxidation levels in the renal cortex and the heart.
      Endothelial nitric oxide immunoreactivity in the renal cortex of both healthy and
      diabetic rats that were treated with GTF was remarkably lower than that found in
      renal cortex of untreated diabetic animals. This study demonstrates that yeast
      derived material, GTF, can inhibit the development of nephropathy that is induced
      by diabetes.

PMID- 16565238
TI  - Chronic kidney disease as a situation of high added risk in hypertensive
      patients.
AB  - Recent guidelines for the management of hypertension have recognized the
      relevance of renal function on cardiovascular prognosis of hypertensive patients.
      In fact, growing evidences have confirmed that as soon as renal function exhibits
      minor derangements, cardiovascular risk starts a continuous rise until the
      development of end-stage renal disease. Both estimated glomerular filtration rate
      and urinary albumin excretion are associated with an increased incidence of
      cardiovascular events and death among hypertensive patients and in general
      population. Consequently, hypertensive patients presenting with chronic kidney
      disease are considered by guidelines as high-risk patients, and strict blood
      pressure control should be considered as a part of an integrative therapeutic
      approach, including correction of anemia, treatment of dyslipidemia, cessation of
      tobacco use, and antiplatelet therapy. This paper briefly reviews the most recent
      evidences about pharmacologic therapies in high-risk patients, focusing on
      benefits related to improvement of cardiovascular risk factors in hypertensive
      patients with chronic kidney disease.

PMID- 16565237
TI  - Preventing renal complications in type 2 diabetes: results of the diabetics
      exposed to telmisartan and enalapril trial.
AB  - Patients with type 2 diabetes are prone to hypertension and persistent protein
      leakage from the kidney (microalbuminuria or macroalbuminuria). A progressive
      decline in renal function can lead to overt diabetic nephropathy and ESRD. The
      likelihood of cardiovascular disease also is increased. Control of hypertension
      is paramount to prevent these life-threatening complications. Agents that target
      the renin-angiotensin system--angiotensin-converting enzyme inhibitors and
      angiotensin II receptor blockers--have been shown to be renoprotective. The
      groundbreaking Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) trial was
      designed to address the absence of comparative data on the long-term effects of
      an angiotensin II receptor blocker versus an angiotensin-converting enzyme
      inhibitor on renoprotection and survival in 250 patients with hypertension and
      early type 2 diabetic nephropathy. The primary purpose of the 5-yr double-blind,
      double-dummy, randomized study was to establish whether 40 to 80 mg of
      telmisartan conferred similar (i.e., noninferior) renoprotection to 10 to 20 mg
      of enalapril as determined by the change from baseline in GFR, measured by the
      plasma clearance of iohexol. Secondary end points included the emergence of ESRD
      and all-cause mortality. Telmisartan was not inferior to enalapril in reducing
      the decline in GFR: Mean annual declines in GFR were 3.7 and 3.3 ml/min per 1.73
      m(2) with telmisartan and enalapril, respectively. During the 5-yr study period,
      no patient developed a serum creatinine >200 micromol/L, and none required
      dialysis. There were only six deaths in each treatment group during the study,
      with half being due to cardiovascular events.

PMID- 16565239
TI  - Randomized clinical trials on surrogate end points: are they useful for
      evaluating cardiovascular and renal disease protection in hypertension? The case
      for yes.
AB  - Hard end point studies represent the best available evidence for demonstrating
      the cardiovascular and renal protection that is achievable with a given treatment
      in hypertensive patients, yet properly designed end point studies require large
      cohorts of patients and long follow-up, are expensive, and do not provide any
      insight on the mechanisms that lead to the clinical manifestations. Studies that
      are based on the incidence of preclinical alterations, i.e., the surrogate end
      points, may circumvent these limitations provided that their relationship with
      the major cardiovascular events is scientifically proved. In this respect, among
      the many surrogate end points that are under investigation, left ventricular
      hypertrophy, microalbuminuria, and treatment-induced diabetes seem most promising
      for replacing the hard end points in view of their undisputed mechanistic
      relationship with the clinical events and of the mounting evidence indicating
      that from their changes it is possible to predict the clinical outcome of
      patients. In addition, the limited resources that are required to carry out this
      kind of investigations make them preferable to hard end point studies for
      anticipating the cardiovascular and renal benefit associated with the use of
      antihypertensive agents.

PMID- 16565240
TI  - Lipids and renal disease.
AB  - Chronic renal disease is accompanied by characteristic abnormalities of lipid
      metabolism, which appear as a consequence of nephrotic syndrome or renal
      insufficiency and are reflected in an altered apolipoprotein profile as well as
      elevated plasma lipid levels. Experimental and clinical studies have suggested a
      correlation between the progression of renal disease and dyslipidemia. High
      cholesterol and triglyceride plasma levels have been demonstrated to be
      independent risk factors for progression of renal disease in humans. The
      underlying pathophysiologic mechanisms for the relationship between lipid levels
      and progression of renal disease are not yet fully understood, although there are
      data that oxidative stress and insulin resistance may mediate the lipid-induced
      renal damage. In the animal model, lipid-lowering agents seem to ameliorate
      glomerular damage, preventing glomerulosclerosis and interstitial fibrosis.
      Although evidence from clinical studies indicates that statin therapy is
      associated with significant benefit in individuals with established chronic renal
      failure, whether lipid reduction can slow the renal functional decline awaits a
      primary renal outcome lipid-lowering therapy study.

PMID- 16565241
TI  - Statins and renal diseases: from primary prevention to renal replacement therapy.
AB  - In glomerular diseases with nephrotic syndrome or protracted severe proteinuria,
      alterations of the lipid metabolism occur and are characterized mainly by
      increase of LDL cholesterol and frequently also of triglycerides and by
      qualitative abnormalities of HDL cholesterol and LDL cholesterol. In all renal
      diseases, when renal insufficiency develops, hyperlipidemia also occurs, with a
      near-elective increase in VLDL and intermediate-density lipoprotein cholesterol
      and a decrease of mature HDL cholesterol. There is clear evidence that these
      abnormalities may induce cardiovascular complications and, probably, also an
      accelerated progression of the renal damage. The inhibitors of 3-hydroxy-3
      methylglutaryl CoA reductase, the so-called statins, are effective in controlling
      hypercholesterolemia, even in the more advanced stages of renal failure and in
      patients who are on maintenance dialysis. This antilipidemic effect of statins
      combines with other effects--antioxidant, anti-inflammatory, immunomodulatory,
      and antithrombotic (called "pleiotropic" effects)--as a result of the inhibition
      of the mevalonate pathway induced by these agents. Also because of these non
      lipid-dependent effects, statins could have an antiatherosclerotic and
      renoprotective effect, which has been demonstrated clearly in vivo on renal cells
      and in experimental models of nephropathy but is still less evident in human
      renal diseases. Ongoing large trials will establish more clearly whether such
      effects are present in renal patients.

PMID- 16565242
TI  - Role of blood pressure targets and specific antihypertensive agents used to
      prevent diabetic nephropathy and delay its progression.
AB  - This study evaluated the comparative effects of antihypertensive agents in
      patients with diabetes and normoalbuminuria and the evidence supporting
      equivalent use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin
      receptor blockers (ARB) in patients with diabetes and micro- or macroalbuminuria.
      A systematic review was conducted by searching for randomized controlled trials
      (RCT) of antihypertensive agent versus placebo or another agent in hypertensive
      or normotensive patients with diabetes and no nephropathy and RCT of ACEi or ARB
      in patients with diabetic nephropathy. Medline, Embase, the Cochrane Controlled
      Trials Register, conference proceedings, and contact with investigators were used
      to identify available evidence. Two investigators independently extracted data
      and assessed quality of trials. Sixteen RCT (7603 patients) of antihypertensive
      agents conducted in patients with diabetes and no nephropathy and 43 (7739
      patients) of ACEi or ARB in patients with diabetic nephropathy were identified. A
      significant reduction in the risk for developing microalbuminuria in patients who
      had diabetes with no nephropathy was demonstrated for ACEi only (six trials, 3840
      patients; relative risk [RR] 0.60; 95% confidence interval [CI] 0.43 to 0.84),
      and in patients with diabetic nephropathy, existing RCT have shown a survival
      benefit of ACEi (20 trials, 2383 patients; RR 0.79; 95% CI 0.63 to 0.99; P =
      0.04) but not ARB (four trials, 3329 patients; RR 0.99; 95% CI 0.85 to 1.17). On
      the basis of available RCT evidence, ACEi are the only agents with proven renal
      benefit in patients who have diabetes with no nephropathy and the only agents
      with proven survival benefit in patients who have diabetes with nephropathy.

PMID- 16565243
TI  - Thiazide diuretics in the treatment of hypertension: an update.
AB  - Thiazide diuretics were the first tolerated efficient antihypertensive drugs that
      significantly reduced cardiovascular morbidity and mortality in placebo
      controlled clinical studies. Although these drugs today still are considered a
      fundamental therapeutic tool for the treatment of hypertensive patients, the
      following considerations should be taken into account. Although there are some
      indications that chlorthalidone can offer additional advantages as compared with
      other compounds, a recent meta-analysis of placebo-controlled trials suggested
      that the beneficial effects of thiazide diuretics could be a class effect.
      Thiazide diuretics must be used at appropriate and/or optimal doses to achieve
      the optimal antihypertensive effect with the smallest occurrence of side effects,
      including alterations in glucose and lipid profiles and hypokalemia. Moreover,
      because thiazide diuretics can increase the incidence of new-onset diabetes,
      especially when combined with beta blockers, caution is advised in using these
      drugs above all in patients who are at high risk for developing diabetes, in whom
      thiazide diuretics should be used at the lowest active dose and possibly in
      combination with drugs that block the renin-angiotensin system. Finally, the
      current debate on whether thiazide diuretics are the first-choice drug for most
      patients with uncomplicated hypertension, as stated in the Seventh Joint National
      Committee Report, or are included in the major classes of antihypertensive agents
      that are suitable for initiation and maintenance of therapy, as reported in the
      European Society of Hypertension-European Society of Cardiology Guidelines,
      derives from different interpretations of controlled clinical trial data on drug
      class comparison and of cost-benefit analyses. However, considering that the
      benefit of antihypertensive drugs seems to be due principally to BP lowering per
      se without definitive evidence of the superiority of a particular drug class and
      that there is no cost-benefit analysis showing the superiority of thiazide
      diuretics, it is believed that these drugs should not be considered as the only
      first-choice drug but included among first-choice drugs.

PMID- 16565244
TI  - Pharmacogenomics and pharmacogenetics of hypertension: update and perspectives-
      the adducin paradigm.
AB  - There is a growing literature on the potential prospective use of genome
      information to enhance success in finding new medicines. An example of a
      prospective efficacy of pharmacogenetic and pharmacogenomics is the detection and
      impact of adducin polymorphism on hypertension. Adducin is a heterodimeric
      cytoskeleton protein, the three subunits of which are encoded by genes (ADD1,
      ADD2, and ADD3) that map to three different chromosomes. A long series of
      parallel studies in the Milan hypertensive rat strain model of hypertension and
      humans indicated that an altered adducin function might cause hypertension
      through an enhanced constitutive tubular sodium reabsorption. In particular, six
      linkage studies, 18 of 20 association studies, and four of five follow-up studies
      that measured organ damage in hypertensive patients support the clinical impact
      of adducing polymorphism. As many modulatory genes and environment affect the
      adducin activity, the context must be taken into account to measure the clinical
      effect size of adducins. Pharmacogenomics is giving an important contribution to
      this end. In particular, the selective advantages of diuretics in preventing
      myocardial infarction and stroke over other antihypertensive therapies that
      produce a similar BP reduction in carriers of the mutated adducin may support new
      strategies that aim to optimize the use of antihypertensive agents for the
      prevention of hypertension-associated organ damage.

PMID- 16565245
TI  - Fewer mega-trials and more clinically oriented studies in hypertension research?
      The case of blocking the renin-angiotensin-aldosterone system.
AB  - In recent years, medical practice has been influenced substantially by several
      factors, including the overwhelming development of evidence-based medicine, which
      is a consequence of the impressive, growing number of large clinical trials, the
      so-called "mega-trials." These clinical studies are designed mostly to
      investigate the effects of drugs or treatments on hard end points that cannot be
      tested by individual physicians in their daily clinical practice. The growing
      role of this epidemiologic approach to medicine, which is based mostly on the
      assessment of the average response or behavior of large populations rather than
      of individuals, is systematically replacing the former knowledge and reference
      points of the physician, as a substitute rather than as an aid. Taking into
      account the case of hypertension and particularly the renin-angiotensin system
      blocking agents, this article reviews the issues and limitations of transferring
      evidence from mega-trials to clinical practice and suggests new strategies to
      make trials more effective and transferable to the case of individual patients.

PMID- 16565246
TI  - Economic evaluation of angiotensin receptor blockers in type 2 diabetes,
      hypertension, and nephropathy.
AB  - There is a rising incidence and prevalence of ESRD as a result of diabetes, with
      poor outcome and growing costs. Recently, two large trials, the Irbesartan
      Diabetic Nephropathy Trial (IDNT) and Reduction of Endpoints in NIDDM with the
      Angiotensin II Antagonist Losartan (RENAAL), showed that angiotensin receptor
      blockers (ARB) are more effective than traditional antihypertensive therapies at
      reducing progression toward ESRD in hypertensive patients with type 2 diabetes
      and overt nephropathy, regardless of changes in BP. The results of these two
      trials were used to compare the costs of ARB with those of renal replacement
      therapy (dialysis and renal transplantation) in an effort to establish whether
      ARB are cost-saving because they delay ESRD. Two different pharmacoeconomic
      approaches were used. With regard to the RENAAL trial, the number of ESRD days on
      losartan therapy as compared with the number of ESRD days on standard
      antihypertensive therapy was calculated, and the difference between the two was
      combined with the costs of ESRD. In the IDNT trial, Markov models were applied to
      assess the economic impact of irbesartan and to extrapolate future clinical and
      cost outcomes. Several economic analyses were performed in the United States and
      in European countries. Applying pharmacoeconomic models showed that treatment
      with ARB was associated with a greater improvement in life expectancy and lower
      total costs compared with amlodipine and standard antihypertensive therapy.
      Therefore, treating patients with type 2 diabetes, nephropathy, and hypertension
      with ARB is life- and cost-saving compared with traditional antihypertensive
      therapy.

PMID- 16565247
TI  - Endothelial function predicts the development of renal damage after combined
      nephrectomy and myocardial infarction.
AB  - It was demonstrated that individual renal endothelial dilatory function of the
      healthy rat predicts susceptibility to subsequent renal damage induced by 5/6
      nephrectomy. In addition, it is reported that myocardial infarction (MI) that was
      performed upon unilateral nephrectomy (UNx) induced highly variable renal damage.
      Therefore, whether the variability in renal damage after MI could be explained by
      the variation in individual renal endothelial function before the induction of
      injury was studied. Endothelium-dependent relaxation to acetylcholine was
      investigated in vitro in small arteries that were isolated from the extirpated
      kidney at UNx. MI was induced 1 wk after UNx by ligation of the left coronary
      artery. Proteinuria and systolic BP were evaluated weekly for 16 wk thereafter
      using metabolic cages and the tail-cuff method, respectively. Upon termination of
      the study, focal glomerulosclerosis was evaluated by histology as an additional
      marker of renal damage. After MI, nephrectomized male Wistar rats (n = 15)
      gradually developed variable proteinuria, ranging from 20 to 507 mg/24 h at week
      16, with an average systolic BP of 131 +/- 7 mmHg. The individual renal
      endothelial function of the healthy rats predicted the extent of renal damage in
      terms of proteinuria (r = -0.62, P = 0.008) and focal glomerulosclerosis (r = 
      0.70, P = 0.003). The individual level of renal endothelial function in the
      healthy rat is able to predict the severity of renal damage that is induced by
      MI. Further exploration of the underlying mechanisms may lead to discovery of
      preventive renoprotective therapies.

PMID- 16565248
TI  - Glomerulotubular junction abnormalities are associated with proteinuria in type 1
      diabetes.
AB  - Glomerulotubular junction abnormalities, frequent in proteinuric patients with
      type 1 diabetes, may contribute to the progressive GFR loss in overt diabetic
      nephropathy. Glomerulotubular junction abnormalities were examined in patients
      who have type 1 diabetes with a wide range of albumin excretion rates (AER).
      Renal biopsies from five normoalbuminuric patients, five microalbuminuric
      patients, six proteinuric patients, and five control subjects were studied by
      light and electron microscopy. Light microscopy specimens were serially sectioned
      to find and classify glomerulotubular junctions. Glomerular structural parameters
      were estimated using stereologic methods. Glomerulotubular junction abnormalities
      were found in 2% of glomeruli from control and normoalbuminuric patients and in
      4% of glomeruli from microalbuminuric patients. In contrast, 71% of glomeruli
      from proteinuric patients had glomerulotubular junction abnormalities, including
      five (8%) atubular glomeruli. Electron microscopy findings were typical of
      diabetic nephropathy. Piece-wise linear regression models with glomerular,
      glomerulotubular junction, and interstitial parameters as independent variables
      provided greater GFR (92%; P < 0.005) and AER (95%; P < 0.01) prediction than
      multiple regression models (81% for GFR and 72% for AER). Thus, glomerular
      adhesions and glomerulotubular junction abnormalities help to explain the
      progressive GFR loss that is associated with onset of proteinuria in type 1
      diabetes. Moreover, nonlinear models provide better fit for structural-functional
      relationships in patients with type 1 diabetes.

PMID- 16565249
TI  - Endothelial dysfunction and the kidney: emerging risk factors for renal
      insufficiency and cardiovascular outcomes in essential hypertension.
AB  - Renal insufficiency in essential hypertension represents the expression of a
      medium- and small-size arteriolopathy characterized by intimal hyperplasia,
      hyalinosis, and smooth muscle cell hypertrophy (nephroangiosclerosis). Because in
      animal models endothelial dysfunction plays a role in this alteration,
      nephroangiosclerosis and the attendant renal insufficiency may be the expression
      of a systemic dysfunction of vascular endothelium. Endothelial function in the
      kidney vasculature of hypertensive individuals has been investigated little
      because studies on the hemodynamic response of the kidney to nitric oxide
      activation and blockade are laborious to perform. There is no direct proof that
      endothelial dysfunction in the forearm or in the coronary circulation is
      paralleled by a similar hemodynamic dysfunction in the kidney. A recent study in
      a large population of patients with essential hypertension showed that,
      independent of other risk factors, the GFR in these patients is strongly related
      to the forearm blood flow response to acetyl choline (an established test of
      endothelial function). Furthermore, in this study, C-reactive protein was
      inversely related to the GFR and with the vasodilatory response to acetyl
      choline, pointing to inflammation as a likely mechanism to explain the
      association between endothelial dysfunction and impaired renal function in
      essential hypertension. A dysfunctional endothelium may represent a critical link
      accounting for the risk for both renal impairment and cardiovascular
      complications in essential hypertension.

PMID- 16565250
TI  - Inflammation as a mediator of the link between mild to moderate renal
      insufficiency and endothelial dysfunction in essential hypertension.
AB  - The relationship among inflammation (plasma high-sensitivity C-reactive protein
      [CRP]), endothelial function (hemodynamic response to acetylcholine [ACh] in the
      forearm), and renal function (serum creatinine and GFR [Modification of Diet in
      Renal Disease formula]) was investigated in 264 never-treated individuals with
      uncomplicated essential hypertension and serum creatinine within the normal
      range. Multiple regression models of renal function (creatinine) were constructed
      in sequence including Framingham risk factors as well the hemodynamic response to
      ACh and plasma CRP. The inclusion of endothelial function into a model based on
      Framingham risk factors added highly significant (P < 0.001) power to this model
      (+5%). Of note, in an alternative model that included CRP (instead of endothelial
      function), the creatinine variance explained by this factor was two times higher
      (+10%) than that associated with endothelial function in the first model. In the
      full model that included both endothelial function and CRP, CRP maintained a much
      stronger independent link with the outcome measure than endothelial function. In
      individuals with untreated, uncomplicated essential hypertension, multivariate
      modeling indicated that inflammation is a crucial mechanism mediating the
      endothelial-renal function link. The proatherogenic potential of inflammation
      associated with subtle impairment in renal function may contribute to the
      cardiovascular risk of essential hypertension.

PMID- 16565251
TI  - Serum uric acid: a risk factor and a target for treatment?
AB  - Serum uric acid was first noted to be associated with increased BP by Frederick
      Mohamed in the 1870s. Although the link was rediscovered periodically over the
      years, it generally was dismissed as a surrogate marker for decreased renal
      function that led to increased uric acid and increased risk for hypertension and
      cardiovascular (CV) disease. Recently, however, several lines of evidence suggest
      that increased serum uric acid may be a significant modifiable risk factor.
      Increased serum uric acid is associated with increased risk for future
      hypertension in several large longitudinal clinical trials as well as an
      independent risk factor for poor CV prognosis. Animal model experiments
      demonstrate that increased serum uric acid causes increased BP that initially is
      reversible but becomes irreversible, salt sensitive, and uric acid independent
      over time. The mechanisms include the direct action of uric acid on smooth muscle
      and vascular endothelial cells. Finally, in adolescents with new-onset essential
      hypertension, the prevalence of elevated serum uric acid is >90%, and preliminary
      clinical trial evidence suggests that agents that lower serum uric acid may lower
      BP in this select population. Although the investigations are still preliminary,
      serum uric acid represents a possible new and intriguing target for the reduction
      of morbidity and mortality associated with hypertension and CV disease.

PMID- 16565252
TI  - Update on erythropoietin treatment: should hemoglobin be normalized in patients
      with chronic kidney disease?
AB  - The partial correction of ESRD anemia by recombinant human erythropoietin (EPO)
      has resulted both in generalized improvement in quality of life and physical
      activity and in reduced mortality and hospitalization rate. The question remains
      as to whether normalizing hemoglobin (Hgb) is desirable in patients with chronic
      kidney disease (CKD). This review provides an analysis and commentary on the
      available reports and, for the most part, randomized, controlled trials on the
      topic. In dialysis patients, normalization of Hgb is associated with improved
      quality of life and exercise capacity but not with reduced mortality and
      hospitalization rate. Moreover, no significant changes in the degree of left
      ventricular hypertrophy have been demonstrated. By contrast, an increased
      mortality rate has been reported for hemodialysis patients with overt
      cardiovascular disease (CVD) when randomly assigned to normal hematocrit by EPO.
      Data regarding patients who have CKD but are not yet on renal replacement therapy
      are scarce, and the effects of EPO on renal disease progression require further
      elucidation through controlled trials. The conclusion that can be drawn from the
      available studies is that Hgb >11 g/dl is the minimum required to achieve
      improved quality of life in patients with CKD, whereas values >12 g/dl are not
      recommended for patients with overt CVD. Finally, Hgb normalization might
      reasonably be restricted to a selected population of younger, employed, and
      active individuals, provided that they do not have CVD.

PMID- 16565253
TI  - Calcium, calcium regulatory hormones, and calcimimetics: impact on cardiovascular
      mortality.
AB  - Calcemia is a risk factor for cardiovascular (CV) events in dialyzed patients.
      The relation between serum calcium and cardiovascular events is continuous and
      linear. Calcium plays a potent role in the genesis of cardiovascular dysfunction,
      particularly by promoting vascular calcification. Parathyroid hormone (PTH) also
      is associated with increased CV risk in both primary and secondary
      hyperparathyroidism. There is a nonlinear relationship between PTH and CV risk;
      both high and low PTH concentrations increase CV risk. The CV risk profile (BP,
      dyslipidemia) is strikingly ameliorated by the administration of calcimimetics.
      Apart from lowering PTH, whether calcimimetics have intrinsic effects on CV risk
      profile is unknown.

PMID- 16565254
TI  - Renal manifestations in the metabolic syndrome.
AB  - The metabolic syndrome, which is characterized by obesity, serum lipid profile
      alterations, hypertension, and fasting hyperglycemia, is very common in developed
      countries, and its prevalence is likely to increase. Chronic kidney disease (CKD)
      also has become a significant public health problem because it affects a
      considerable proportion of the adult population and is a major risk factor for
      cardiovascular disease and premature death. Although it is widely known that the
      metabolic syndrome is a major risk factor for the development of type 2 diabetes
      and cardiovascular disease, its precise relationship with the risk for renal
      impairment only recently has been clarified: Patients with the metabolic syndrome
      are at significantly higher risk for microalbuminuria and/or CKD, and the level
      of risk is related to the number of components of the syndrome itself. Although
      it is difficult to discriminate the detrimental renal effects of the metabolic
      syndrome from those of hypertension and impaired glucose metabolism, its other
      aspects (particularly obesity) may favor independently the development of renal
      abnormalities and may be considered new modifiable risk factors for CKD. These
      observations provide a rationale for intervention studies that aim to verify
      whether treating the many components of the metabolic syndrome can effectively
      prevent the development and progression of renal damage.

PMID- 16565255
TI  - Renal protection in diabetes: role of glycemic control.
AB  - Diabetes is the most common cause of ESRD in Western countries. This article
      describes the impact of glycemic control in the various stages of the disease and
      considers the impact of tight glycemic control on the development and progression
      of diabetic nephropathy (DN). The Diabetes Control and Complications Trial and
      the United Kingdom Prospective Diabetic Study have demonstrated in type 1 and
      type 2 diabetes that intensive glycemic control significantly reduces the risk
      for development of microalbuminuria. Although observational studies suggest an
      impact of glycemia also on the progression of DN, fewer data are available on the
      impact of improved metabolic control in secondary prevention. The long-term
      follow-up of the patients who participated in the Diabetes Control and
      Complications Trial (Epidemiology of Diabetes Interventions and Complications
      Study) demonstrated a sustained effect of previous tight glycemic control on both
      development and progression of DN. Finally, long-term normoglycemia, achieved by
      pancreas transplantation, is able not only to prevent the development of early
      diabetic glomerulopathy in kidney transplant recipients but also to halt
      progression and induce regression of the established diabetic renal lesions in
      nonuremic patients. Taken together, these studies strongly demonstrate that
      improvement in glucose control is the most important therapeutic approach in
      primary prevention. Tight glycemic control also is important in slowing
      progression of DN, and if blood glucose is normalized, then regression of DN can
      be achieved. Therefore, a target of glycated hemoglobin levels <7% should be
      recommended in all patients with diabetes.

PMID- 16565256
TI  - Prevention and treatment of diabetic renal disease in type 2 diabetes: the
      BENEDICT study.
AB  - Diabetic nephropathy (DN) is the leading cause of end-stage renal failure in
      Western countries and carries an increased risk for cardiovascular mortality.
      Studies have identified a number of factors that play a part in the development
      of DN. Among them, hypertension and proteinuria are the most important. In the
      early stages of DN, when albumin is present in the urine in very low quantities
      (microalbuminuria) and an increase is seen in BP, there is no loss of filtrate
      and patients respond well to prophylactic measures. Microalbuminuria is
      considered an early marker of DN. Prevention of the onset of microalbuminuria,
      therefore, could be considered as the primary means of preventing DN. The Bergamo
      Nephrologic Diabetes Complication Trial (BENEDICT) was a prospective, randomized,
      double-blind, parallel-group study that was organized in two phases. Phase A
      included 1204 patients and was aimed at assessing the efficacy of the angiotensin
      converting enzyme (ACE) inhibitor trandolapril, the non-dihydropyridine calcium
      channel blocker verapamil, and the trandolapril plus verapamil combination as
      compared with placebo in prevention of microalbuminuria in hypertensive patients
      with type 2 diabetes and normal urinary albumin excretion rate. Phase B was aimed
      at assessing the efficacy of the combination as compared with trandolapril alone
      in prevention of macroalbuminuria in patients with microalbuminuria. The BENEDICT
      Phase A study showed that DN can be prevented by ACE inhibitor therapy. The
      beneficial effect of ACE inhibition is not enhanced by combined non
      dihydropyridine calcium channel blocker therapy. The apparent advantage of ACE
      inhibitors over other agents includes a protective effect on the kidney against
      the development of microalbuminuria, which is a major risk factor for
      cardiovascular events and death in this population.

PMID- 16565257
TI  - Importance of blood pressure control in chronic kidney disease.
AB  - Arterial hypertension together with proteinuria is one of the most important
      factors associated with the progression of both diabetic and nondiabetic chronic
      kidney disease. In this review, the role of hypertension and proteinuria in renal
      disease progression, the BP target that should be achieved to slow the
      progression of renal damage, and the influence of baseline and current
      proteinuria on the renoprotective effects of antihypertensive therapy are
      discussed thoroughly. The interaction between the renoprotective effects of
      specific antihypertensive agents--mostly angiotensin-converting enzyme inhibitors
      and angiotensin receptor blockers--and the level of achieved BP also are
      evaluated. The body of evidence provided by several studies emphasizes the
      importance of both lowering BP and inhibiting the renin-angiotensin system as
      specific goals for renal and cardiovascular protection in chronic kidney disease.

PMID- 16565258
TI  - Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction.
AB  - A "two-hit" hypothesis predicts a second somatic hit, in addition to the germline
      mutation, as a prerequisite to cystogenesis and has been proposed to explain the
      focal nature for renal cyst formation in autosomal dominant polycystic kidney
      disease (ADPKD). It was reported previously that Pkd1(null/null) mouse kidney
      epithelial cells are unresponsive to flow stimulation. This report shows that
      Pkd1(+/null) cells are capable of responding to mechanical flow stimulation by
      changing their intracellular calcium concentration in a manner similar to that of
      wild-type cells. This paper reports that human renal epithelia require a higher
      level of shear stress to evoke a cytosolic calcium increase than do mouse renal
      epithelia. Both immortalized and primary cultured renal epithelial cells that
      originate from normal and nondilated ADPKD human kidney tubules display normal
      ciliary expression of the polycystins and respond to fluid-flow shear stress with
      the typical change in cytosolic calcium. In contrast, immortalized and primary
      cultured cyst-lining epithelial cells from ADPKD patients with mutations in PKD1
      or with abnormal ciliary expression of polycystin-1 or -2 were not responsive to
      fluid shear stress. These data support a two-hit hypothesis as a mechanism of
      cystogenesis. This report proposes that calcium response to fluid-flow shear
      stress can be used as a readout of polycystin function and that loss of
      mechanosensation in the renal tubular epithelia is a feature of PKD cysts.

PMID- 16565259
TI  - Hemodialysis vascular access dysfunction: a cellular and molecular viewpoint.
AB  - Hemodialysis vascular access dysfunction is a major cause of morbidity and
      hospitalization in the hemodialysis population. The major cause of hemodialysis
      vascular access dysfunction is venous stenosis as a result of neointimal
      hyperplasia. Despite the magnitude of the clinical problem, however, there has
      been a paucity of novel therapeutic interventions in this field. This is in
      marked contrast to a recent plethora of targeted interventions for the treatment
      of arterial neointimal hyperplasia after coronary angioplasty. The reasons for
      this are two-fold. First there has been a relative lack of cellular and molecular
      research that focuses on venous neointimal hyperplasia in the specific setting of
      hemodialysis vascular access. Second, there have been inadequate efforts by the
      nephrology community to translate the recent advances in molecular and
      interventional cardiology into therapies for hemodialysis vascular access. This
      review therefore (1) briefly examines the different forms of hemodialysis
      vascular access that are available, (2) describes the pathology and pathogenesis
      of hemodialysis vascular access dysfunction in both polytetrafluoroethylene
      grafts and native arteriovenous fistulae, (3) reviews recent concepts about the
      pathogenesis of vascular stenosis that could potentially be applied in the
      setting of hemodialysis vascular access dysfunction, (4) summarizes novel
      experimental and clinical therapies that could potentially be used in the setting
      of hemodialysis vascular access dysfunction, and, finally, (5) offers some broad
      guidelines for future innovative translational and clinical research in this area
      that hopefully will reduce the huge clinical morbidity and economic costs that
      are associated with this condition.

PMID- 16565261
TI  - Associations between changes in hemoglobin and administered erythropoiesis
      stimulating agent and survival in hemodialysis patients.
AB  - Although treating anemia of chronic kidney disease by erythropoiesis-stimulating
      agents (ESA) may improve survival, most studies have examined associations
      between baseline hemoglobin values and survival and ignored variations in
      clinical and laboratory measures over time. It is not clear whether longitudinal
      changes in hemoglobin or administered ESA have meaningful associations with
      survival after adjustment for time-varying confounders. With the use of time
      dependent Cox regression models, longitudinal associations were examined between
      survival and quarterly (13-wk averaged) hemoglobin values and administered ESA
      dose in a 2-yr (July 2001 to June 2003) cohort of 58,058 maintenance hemodialysis
      patients from a large dialysis organization (DaVita) in the United States. After
      time-dependent and multivariate adjustment for case mix, quarterly varying
      administered intravenous iron and ESA doses, iron markers, and nutritional
      status, hemoglobin levels between 12 and 13 g/dl were associated with the
      greatest survival. Among prevalent patients, the lower range of the recommended
      Kidney Disease Quality Outcomes Initiative hemoglobin target (11 to 11.5 g/dl)
      was associated with a higher death risk compared with the 11.5- to 12-g/dl range.
      A decrease or increase in hemoglobin over time was associated with higher or
      lower death risk, respectively, independent of baseline hemoglobin.
      Administration of any dose of ESA was associated with better survival, whereas
      among those who received ESA, requiring higher doses were surrogates of higher
      death risk. In this observational study, greater survival was associated with a
      baseline hemoglobin between 12 and 13 g/dl, treatment with ESA, and rising
      hemoglobin. Falling hemoglobin and requiring higher ESA doses were associated
      with decreased survival. Randomized clinical trials are required to examine these
      associations.

PMID- 16565260
TI  - A locus for renal malformations including vesico-ureteric reflux on chromosome
      13q33-34.
AB  - Congenital anomalies of kidney and urinary tract (CAKUT), including vesico
      ureteric reflux (VUR), are major causes of ESRD in childhood. Herein is reported
      evidence for a locus on 13q33q34 associated with CAKUT. Deletion mapping of
      chromosome 13q was performed in four children with CAKUT using 31 microsatellite
      markers on peripheral blood genomic DNA that was obtained from the patients and
      their parents. mRNA expression of the positional candidate genes was compared
      with sequences in electronic databases in silico and also studied in adult and
      fetal mouse kidneys using reverse transcription-PCR. The children (three girls;
      age range 5 to 17 yr) had varying severity of developmental delay and other organ
      system involvement. The spectrum of CAKUT included high-grade VUR (n = 2), renal
      dysplasia (n = 2), and hydronephrosis (n = 1). Both the children with VUR had
      evidence of renal failure with one of them developing ESRD. Deletion mapping
      identified a 7-Mb critical region flanked by markers D13S1311 and D13S285. There
      are 33 genes (12 known; 21 computer predicted) in this region. In silico
      expression studies showed matches for 14 of these genes in the kidneys and 10 in
      the bladder expressed sequenced tags databases. Mouse kidney studies showed that
      of the 24 genes examined, several had variable expression through the different
      stages of renal development, whereas five of the genes were not expressed at all.
      Herein is reported a new locus on chromosome 13q33q34 that can be associated with
      VUR with several genes showing mRNA expression patterns that suggest their
      potential for involvement in renal/urinary tract developmental anomalies.

PMID- 16565262
TI  - Cancer, quackery and the vernacular meanings of hope in 1950s America.
AB  - Hope was central to cancer control in twentieth-century America. Physicians
      placed great store in its power to persuade people to seek medical help as early
      as possible in the development of the disease, when it was most amenable to
      treatment; to maintain patients' loyalty through what could be a long, painful
      and uncertain course of therapy; and to encourage doubts about alternative
      healers. Some also argued that hope could have beneficial therapeutic and
      psychological effects for patients. However, we know very little about its
      meanings for the public. Focusing on a large collection of letters written to the
      Food and Drug Administration in the 1950s concerning an anti-quackery campaign,
      this article explores how men and women responded to the competing messages of
      hope promoted by orthodox cancer organizations and by alternative healers. It
      asks: What did hope mean to such men and women? How did they construct this
      meaning? How did they decide which treatments were hopeful and which were not?
      And, how did they use hope to imagine the social world of cancer? In short, this
      article explores the vernacular meanings, epistemologies, and imaginative uses of
      hope among Americans in the mid-twentieth century.

PMID- 16565263
TI  - Tight glycaemic control in acute exacerbations of COPD.

PMID- 16565264
TI  - The childhood asthma epidemic.

PMID- 16565265
TI  - Training in the operating theatre: is it safe?

PMID- 16565266
TI  - British Thoracic Society winter meeting 2005.

PMID- 16565267
TI  - Serum carotenoids, vitamins A and E, and 8 year lung function decline in a
      general population.
AB  - BACKGROUND: Oxidative stress is thought to have a major role in the pathogenesis
      of airway obstruction. A study was undertaken to determine whether subjects with
      low levels of antioxidants (serum beta-carotene, alpha-carotene, vitamins A and
      E) would be at a higher risk of accelerated decline in forced expiratory volume
      in 1 second (FEV1) as their lungs would be less protected against oxidative
      stress. METHODS: 1194 French subjects aged 20-44 years were examined in 1992 as
      part of the European Community Respiratory Health Survey (ECRHS); 864 were
      followed up in 2000 and 535 (50% men, 40% lifelong non-smokers) had complete data
      for analysis. RESULTS: During the 8 year study period the mean annual decrease in
      FEV1 (adjusted for sex, centre, baseline FEV1, age, smoking, body mass index and
      low density lipoprotein cholesterol) was 29.8 ml/year. The rate of decrease was
      lower for the subjects in tertile I of beta-carotene at baseline than for those
      in the two other tertiles (-36.5 v -27.6 ml/year; p = 0.004). An increase in beta
      carotene between the two surveys was associated with a slower decline in FEV1. No
      association was observed between alpha-carotene, vitamin A, or vitamin E and
      FEV(1) decline. However, being a heavy smoker (> or =20 cigarettes/day) in
      combination with a low level of beta-carotene or vitamin E was associated with
      the steepest decline in FEV1 (-52.5 ml/year, p = 0.0002 and -50.1 ml/year, p =
      0.010, respectively). CONCLUSIONS: These results strongly suggest that beta
      carotene protects against the decline in FEV1 over an 8 year period in the
      general population, and that beta-carotene and vitamin E are protective in heavy
      smokers.

PMID- 16565269
TI  - Trends in sales of inhaled corticosteroids and asthma outcomes in Singapore.

PMID- 16565268
TI  - COPD exacerbations . 3: Pathophysiology.
AB  - Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with
      increased morbidity and mortality. The effective management of COPD exacerbations
      awaits a better understanding of the underlying pathophysiological mechanisms
      that shape its clinical expression. The clinical presentation of exacerbations of
      COPD is highly variable and ranges from episodic symptomatic deterioration that
      is poorly responsive to usual treatment, to devastating life threatening events.
      This underscores the heterogeneous physiological mechanisms of this complex
      disease, as well as the variation in response to the provoking stimulus. The
      derangements in ventilatory mechanics, muscle function, and gas exchange that
      characterise severe COPD exacerbations with respiratory failure are now well
      understood. Critical expiratory flow limitation and the consequent dynamic lung
      hyperinflation appear to be the proximate deleterious events. Similar basic
      mechanisms probably explain the clinical manifestations of less severe
      exacerbations of COPD, but this needs further scientific validation. In this
      review we summarise what we have learned about the natural history of COPD
      exacerbations from clinical studies that have incorporated physiological
      measurements. We discuss the pathophysiology of clinically stable COPD and
      examine the impact of acutely increased expiratory flow limitation on the
      compromised respiratory system. Finally, we review the chain of physiological
      events that leads to acute ventilatory insufficiency in severe exacerbations.

PMID- 16565270
TI  - Non-invasive monitoring of CO2 levels in patients using NIV for AECOPD.

PMID- 16565271
TI  - A&E department: a missed opportunity for diagnosis of TB?

PMID- 16565272
TI  - Per lesion analysis is misleading.

PMID- 16565273
TI  - Pulmonary artery pseudoaneurysm secondary to metastatic angiosarcoma.

PMID- 16565275
TI  - Extending the synergy model to preceptorship: a preliminary proposal.

PMID- 16565276
TI  - End-of-life decision making in ICU.

PMID- 16565277
TI  - The role of critical care nurses in the organ donation breakthrough
      collaborative.

PMID- 16565280
TI  - Organ donation breakthrough collaborative: increasing organ donation through
      system redesign.

PMID- 16565281
TI  - Caring for transplant recipients in a nontransplant setting.

PMID- 16565283
TI  - Timely referral of potential organ donors.

PMID- 16565282
TI  - End-of-life decision making, organ donation, and critical care nurses.

PMID- 16565284
TI  - Intensive management of organ donors to maximize transplantation.

PMID- 16565285
TI  - Maximizing organ donation opportunities through donation after cardiac death.

PMID- 16565286
TI  - Brain death in infants and children.

PMID- 16565287
TI  - A study of the presumptive approach to consent for organ donation: a new solution
      to an old problem.

PMID- 16565288
TI  - Ask the experts. Isotonic sodium chloride solution versus heparin in pressure
      monitoring systems.

PMID- 16565290
TI  - Student reference packet for the intensive care unit rotation.

PMID- 16565291
TI  - A specific heat shock protein enhances the expression of mammalian olfactory
      receptor proteins.
AB  - Multiple trials failed to express significant amounts of olfactory receptors in
      heterologous cells as they are typically retained in the endoplasmic reticulum
      (ER). Evidence is accumulating that cell-type-specific accessory proteins
      regulate the folding of olfactory receptors, their exit from the ER, and the
      trafficking to the plasma membrane of the olfactory cilia where the receptors
      gain access to odorants. We found Hsc70t, a testis-enriched variant of the Hsp70
      family of heat shock proteins which is specifically expressed in post-meiotic
      germ cells, in the olfactory epithelium of mouse and human. Cotransfected HEK293
      cells with Hsc70t and different green fluorescent protein-tagged odorant
      receptors (ORs) from mouse and man showed a significantly enhanced OR expression.
      Hsc70t expression also changed the amount of cells functionally expressing
      olfactory receptors at the cell surface as the number of cells responding to
      odorants in Ca2+-imaging experiments significantly increased. Our results show
      that Hsc70t helps expression of ORs in heterologous cell systems and helped the
      characterization of an "orphan" human olfactory receptor.

PMID- 16565293
TI  - Role of the prefrontal cortex in the foreperiod effect: TMS evidence for dual
      mechanisms in temporal preparation.
AB  - The involvement of right dorsolateral prefrontal cortex (rDLPFC) in explicit
      temporal processing is well documented. Conversely, the role of this area in
      implicit temporal processing (e.g., foreperiod [FP] effect) is still poorly
      understood. The FP effect, usually observed when a range of variable FPs occur
      randomly and equiprobably, consists of reaction times (RTs) decreasing as the FP
      increases. Moreover, in such paradigms, RTs increase as a function of the
      preceding FP (i.e., sequential effects). Patients with lesions of the rDLPFC do
      not show the typical FP effect. The present study aimed to replicate these
      results in healthy adults using transcranial magnetic stimulation (TMS) and to
      further investigate whether any change of sequential effects follows a reduction
      of the FP effect. The results of 2 experiments (with simple and choice RT tasks,
      respectively) indicate that the FP effect was significantly reduced after TMS
      over the rDLPFC, whereas no effect was observed after stimulation of a left
      contralateral site and the right angular gyrus. Conversely, sequential effects
      were not influenced by TMS. A dual-process model of the FP phenomena is proposed
      to interpret the dissociation found between the 2 effects.

PMID- 16565292
TI  - Hemispheric asymmetry for auditory processing in the human auditory brain stem,
      thalamus, and cortex.
AB  - We report evidence for a context- and not stimulus-dependent functional asymmetry
      in the left and right human auditory midbrain, thalamus, and cortex in response
      to monaural sounds. Neural activity elicited by left- and right-ear stimulation
      was measured simultaneously in the cochlear nuclei, inferior colliculi (ICs),
      medial geniculate bodies (MGBs), and auditory cortices (ACs) in 2 functional
      magnetic resonance imaging experiments. In experiment 1, pulsed noise was
      presented monaurally to either ear, or binaurally, simulating a moving sound
      source. In experiment 2, only monaural sounds were presented. The results show a
      modulation of the neural responses to monaural sounds by the presence of binaural
      sounds at a time scale of tens of seconds: In the absence of binaural
      stimulation, the left and right ICs, MGBs, and ACs responded stronger to
      stimulation of the contralateral ear. When blocks of binaural stimuli were
      interspersed in the sound sequence, the contralateral preference vanished in
      those structures in the right hemisphere. The resulting hemispheric asymmetry was
      similar to the asymmetry demonstrated for spatial sound processing. Taken
      together, the data demonstrate that functional asymmetries in auditory processing
      are modulated by context. The observed long time constant suggests that this
      effect results from a "top-down" mechanism.

PMID- 16565294
TI  - Visual quality determines the direction of neural repetition effects.
AB  - One ubiquitous finding in functional magnetic resonance imaging studies is that
      repeated stimuli elicit lower responses than novel stimuli. In apparent
      contradiction, some studies have reported the exact opposite effect--greater
      responses to repeated than novel stimuli--in many of the same brain regions.
      Interestingly, these latter enhancement effects are typically obtained when
      stimuli have been degraded. To explore this observation, the present study
      examines the degree to which visual quality mediates repetition effects in a
      stimulus-selective ventral visual area. Subjects were presented with grayscale
      photographs of scenes that were either near or substantially above visual
      threshold, as determined by calibrating image contrast to behavioral performance.
      The presentation of 2 identical high-contrast scenes elicited lower blood oxygen
      level-dependent (BOLD) responses than the presentation of 2 different high
      contrast scenes (repetition attenuation). Conversely, the presentation of 2
      identical low-contrast scenes elicited greater BOLD responses than the
      presentation of 2 different low-contrast scenes (repetition enhancement).
      Neurophysiological studies suggest that repetition attenuation in ventral visual
      areas may reflect the reactivation of perceptual representations that have become
      sparse and selective as a result of prior experience, whereas repetition
      enhancement may reflect spared access to existing representations by severely
      degraded input.

PMID- 16565295
TI  - Structural investigation of disordered stress proteins. Comparison of full-length
      dehydrins with isolated peptides of their conserved segments.
AB  - Dehydrins constitute a class of intrinsically disordered proteins that are
      expressed under conditions of water-related stress. Characteristic of the
      dehydrins are some highly conserved stretches of seven to 17 residues that are
      repetitively scattered in their sequences, the K-, S-, Y-, and Lys-rich segments.
      In this study, we investigate the putative role of these segments in promoting
      structure. The analysis is based on comparative analysis of four full-length
      dehydrins from Arabidopsis (Arabidopsis thaliana; Cor47, Lti29, Lti30, and Rab18)
      and isolated peptide mimics of the K-, Y-, and Lys-rich segments. In
      physiological buffer, the circular dichroism spectra of the full-length dehydrins
      reveal overall disordered structures with a variable content of poly-Pro helices,
      a type of elongated secondary structure relying on bridging water molecules.
      Similar disordered structures are observed for the isolated peptides of the
      conserved segments. Interestingly, neither the full-length dehydrins nor their
      conserved segments are able to adopt specific structure in response to altered
      temperature, one of the factors that regulate their expression in vivo. There is
      also no structural response to the addition of metal ions, increased protein
      concentration, or the protein-stabilizing salt Na(2)SO(4). Taken together, these
      observations indicate that the dehydrins are not in equilibrium with high-energy
      folded structures. The result suggests that the dehydrins are highly evolved
      proteins, selected to maintain high configurational flexibility and to resist
      unspecific collapse and aggregation. The role of the conserved segments is thus
      not to promote tertiary structure, but to exert their biological function more
      locally upon interaction with specific biological targets, for example, by acting
      as beads on a string for specific recognition, interaction with membranes, or
      intermolecular scaffolding. In this perspective, it is notable that the Lys-rich
      segment in Cor47 and Lti29 shows sequence similarity with the animal chaperone
      HSP90.

PMID- 16565296
TI  - Gene expression profiling using cDNA microarray analysis of the sexual
      reproduction stage of the unicellular charophycean alga Closterium peracerosum
      strigosum-littorale complex.
AB  - The desmid Closterium peracerosum-strigosum-littorale complex, which is the
      closest unicellular sister to land plants, is the best characterized of the
      charophycean green algae with respect to the process of sexual reproduction. To
      elucidate the molecular mechanism of intercellular communication during sexual
      reproduction, we created a normalized cDNA library from mixed cells of the sexual
      and the vegetative phases and generated a cDNA microarray. In total, 3,236
      expressed sequence tags, which were classified into 1,615 nonredundant groups,
      were generated for cDNA microarray construction. Candidate genes for key factors
      involved in fertilization, such as those that encode putative receptor-like
      protein kinase, leucine-rich-repeat receptor-like protein, and sex pheromone
      homologs, were up-regulated during sexual reproduction and/or by the addition of
      the purified sex pheromones, and the expression patterns of these genes were
      confirmed by quantitative real-time polymerase chain reaction analysis. This
      first transcriptome profile of Closterium will provide critical clues as to the
      mechanism and evolution of intercellular communication between the egg and sperm
      cells of land plants.

PMID- 16565297
TI  - Identification of primary target genes of phytochrome signaling. Early
      transcriptional control during shade avoidance responses in Arabidopsis.
AB  - The phytochrome (phy) photoreceptors modulate plant development after perception
      of light. Upon illumination of etiolated seedlings, phys initiate a
      transcriptional cascade by directly transducing light signals to the promoters of
      genes encoding regulators of morphogenesis. In light-grown plants, however,
      little is known about the transcriptional cascade modulated by phys in response
      to changes in light. The phy entry points in this cascade are completely unknown.
      We are particularly interested in the shade avoidance syndrome (SAS). Here we
      describe a subset of six genes whose expression is rapidly modulated by phys
      during both deetiolation and SAS in Arabidopsis (Arabidopsis thaliana). Using
      cycloheximide, we provide evidence that four of these phy rapidly regulated (PAR)
      genes are direct targets of phy signaling during SAS, revealing these genes as
      upstream components of the transcriptional cascade. Promoter-beta-glucuronidase
      fusions confirmed that PAR genes are photoregulated at the transcriptional level.
      Analysis of gene expression in light signal transduction mutants showed that COP1
      and DET1 (but not DET2 or HY5) play a role in modulating PAR expression in
      response to shade in light-grown seedlings. Moreover, genetic analyses showed
      that one of the genes identified as a direct target of phy signaling was phy
      interacting factor 3-like-1 (PIL1). PIL1 has previously been implicated in SAS in
      response to transient shade, but we show here that it also plays a key role in
      response to long-term shade. The action of PIL1 was particularly apparent in a
      phyB background, suggesting an important negative role for PIL1 under dense
      vegetation canopies.

PMID- 16565298
TI  - alpha-Tocopherol plays a role in photosynthesis and macronutrient homeostasis of
      the cyanobacterium Synechocystis sp. PCC 6803 that is independent of its
      antioxidant function.
AB  - alpha-Tocopherol is synthesized exclusively in oxygenic phototrophs and is known
      to function as a lipid-soluble antioxidant. Here, we report that alpha-tocopherol
      also has a novel function independent of its antioxidant properties in the
      cyanobacterium Synechocystis sp. PCC 6803. The photoautotrophic growth rates of
      wild type and mutants impaired in alpha-tocopherol biosynthesis are identical,
      but the mutants exhibit elevated photosynthetic activities and glycogen levels.
      When grown photomixotrophically with glucose (Glc), however, these mutants cease
      growth within 24 h and exhibit a global macronutrient starvation response
      associated with nitrogen, sulfur, and carbon, as shown by decreased
      phycobiliprotein content (35% of the wild-type level) and accumulation of the
      nblA1-nblA2, sbpA, sigB, sigE, and sigH transcripts. Photosystem II activity and
      carboxysome synthesis are lost in the tocopherol mutants within 24 h of
      photomixotrophic growth, and the abundance of carboxysome gene (rbcL, ccmK1,
      ccmL) and ndhF4 transcripts decreases to undetectable levels. These results
      suggest that alpha-tocopherol plays an important role in optimizing
      photosynthetic activity and macronutrient homeostasis in Synechocystis sp. PCC
      6803. Several lines of evidence indicate that increased oxidative stress in the
      tocopherol mutants is unlikely to be the underlying cause of photosystem II
      inactivation and Glc-induced lethality. Interestingly, insertional inactivation
      of the pmgA gene, which encodes a putative serine-threonine kinase similar to
      RsbW and RsbT in Bacillus subtilis, results in a similar increase in glycogen and
      Glc-induced lethality. Based on these results, we propose that alpha-tocopherol
      plays a nonantioxidant regulatory role in photosynthesis and macronutrient
      homeostasis through a signal transduction pathway that also involves PmgA.

PMID- 16565299
TI  - Evidence for two-pore domain potassium channels in rat cerebral arteries.
AB  - Little is known about the presence and function of two-pore domain K(+) (K(2P))
      channels in vascular smooth muscle cells (VSMCs). Five members of the K(2P)
      channel family are known to be directly activated by arachidonic acid (AA). The
      purpose of this study was to determine 1) whether AA-sensitive K(2P) channels are
      expressed in cerebral VSMCs and 2) whether AA dilates the rat middle cerebral
      artery (MCA) by increasing K+ currents in VSMCs via an atypical K+ channel. RT
      PCR revealed message for the following AA-sensitive K(2P) channels in rat MCA:
      tandem of P domains in weak inward rectifier K+ (TWIK-2), TWIK-related K+ (TREK-1
      and TREK-2), TWIK-related AA-stimulated K+ (TRAAK), and TWIK-related halothane
      inhibited K+ (THIK-1) channels. However, in isolated VSMCs, only message for TWIK
      2 was found. Western blotting showed that TWIK-2 is present in MCA, and
      immunohistochemistry further demonstrated its presence in VSMCs. AA (10-100
      microM) dilated MCAs through an endothelium-independent mechanism. AA-induced
      dilation was not affected by inhibition of cyclooxygenase, epoxygenase, or
      lipoxygenase or inhibition of classical K+ channels with 10 mM TEA, 3 mM 4
      aminopyridine, 10 microM glibenclamide, or 100 microM Ba2+. AA-induced dilations
      were blocked by 50 mM K+, indicating involvement of a K+ channel. AA (10 microM)
      increased whole cell K+ currents in dispersed cerebral VSMCs. AA-induced currents
      were not affected by inhibitors of the AA metabolic pathways or blockade of
      classical K+ channels. We conclude that AA dilates the rat MCA and increases K+
      currents in VSMCs via an atypical K+ channel that is likely a member of the K(2P)
      channel family.

PMID- 16565301
TI  - Regional myocardial ischemia-induced activation of MAPKs is associated with
      subcellular redistribution of caveolin and cholesterol.
AB  - Ischemia-reperfusion activates ERK and p38 MAPK in cardiac membranes, but the
      role of caveolae in MAPK signaling during this stress has not been studied. The
      purpose of this study was to determine the effect of in vivo myocardial ischemia
      reperfusion on the level and distribution of caveolin-1 and -3 and cholesterol as
      well as MAPK activation in caveolin-enriched fractions. Adult male rats were
      subjected to in vivo regional myocardial ischemia induced by 25 min of coronary
      artery occlusion and 10 min (n = 5) or 2 h (n = 4) of reperfusion. Another group
      of rats served as appropriate nonischemic time controls (n = 4). A discontinuous
      sucrose density gradient was used to isolate caveolae/lipid rafts from ischemic
      and nonischemic heart tissue. Caveolin-1 and -3, as well as cholesterol, were
      enriched in the light fractions. A redistribution of caveolin-3 and a reduction
      in caveolin-1 and cholesterol levels in the light fractions occurred after 10 min
      of reperfusion. The ERKs were activated in ischemic zone light and heavy
      fractions by 10 min of reperfusion. p44 ERK was activated after 2 h of
      reperfusion only in the light fractions, whereas p42 ERK phosphorylation was
      increased in the light and heavy fractions. Although no p38 MAPK activation
      occurred after 10 min of reperfusion, 2 h of reperfusion caused significant
      activation of p38 MAPK in nonischemic zone light and heavy fractions. These
      results show the importance of caveolar membrane/lipid rafts in MAPK signaling
      and suggest that subcellular compartmentation of p44/p42 ERKs and p38 MAPK may
      play distinct roles in the response to myocardial ischemia-reperfusion.

PMID- 16565300
TI  - Postural hypocapnic hyperventilation is associated with enhanced peripheral
      vasoconstriction in postural tachycardia syndrome with normal supine blood flow.
AB  - Previous investigations have demonstrated a subset of postural tachycardia
      syndrome (POTS) patients characterized by normal peripheral resistance and blood
      volume while supine but thoracic hypovolemia and splanchnic blood pooling while
      upright secondary to splanchnic hyperemia. Such "normal-flow" POTS patients often
      demonstrate hypocapnia during orthostatic stress. We studied 20 POTS patients (14
      23 yr of age) and compared them with 10 comparably aged healthy volunteers. We
      measured changes in heart rate, blood pressure, heart rate and blood pressure
      variability, arm and leg strain-gauge occlusion plethysmography, respiratory
      impedance plethysmography calibrated against pneumotachography, end-tidal partial
      pressure of carbon dioxide (Pet(CO2)), and impedance plethysmographic indexes of
      blood volume and blood flow within the thoracic, splanchnic, pelvic (upper leg),
      and lower leg regional circulations while supine and during upright tilt to 70
      degrees. Ten POTS patients demonstrated significant hyperventilation and
      hypocapnia (POTS(HC)) while 10 were normocapnic with minimal increase in postural
      ventilation, comparable to control. While relative splanchnic hypervolemia and
      hyperemia occurred in both POTS groups compared with controls, marked enhancement
      in peripheral vasoconstriction occurred only in POTS(HC) and was related to
      thoracic blood flow. Variability indexes suggested enhanced sympathetic
      activation in POTS(HC) compared with other subjects. The data suggest enhanced
      cardiac and peripheral sympathetic excitation in POTS(HC).

PMID- 16565302
TI  - STAT-3 activation is necessary for ischemic preconditioning in hypertrophied
      myocardium.
AB  - The JAK-STAT pathway is activated in the early and late phases of ischemic
      preconditioning (IPC) in normal myocardium. The role of this pathway and the
      efficacy of IPC in hypertrophied hearts remain largely unknown. We hypothesized
      that phosphorylated STAT-3 (pSTAT-3) is necessary for effective IPC in pressure
      overload hypertrophy. Male Sprague-Dawley rats 8 wk after thoracic aortic
      constriction (TAC) or sham operation underwent echocardiography and Langendorff
      perfusion. Randomized hearts were subjected to 30 min of global ischemia and 120
      min of reperfusion with or without IPC in the presence or absence of the JAK-2
      inhibitor AG-490 (AG). Functional recovery and STAT activation were assessed. TAC
      rats had a 31% increase in left ventricular mass (1,347 +/- 58 vs. 1,028 +/- 43
      mg, TAC vs. sham, P < 0.001), increased anterior and posterior wall thickness but
      no difference in ejection fraction compared with sham-operated rats. In TAC, IPC
      improved end-reperfusion maximum first derivative of developed pressure
      (+dP/dt(max); 4,648 +/- 309 vs. 2,737 +/- 343 mmHg/s, IPC vs. non-IPC, P < 0.05)
      and minimum -dP/dt (-dP/dt(min); -2,239 +/- 205 vs. -1,215 +/- 149 mmHg/s, IPC
      vs. non-IPC, P < 0.05). IPC increased nuclear pSTAT-1 and pSTAT-3 in sham
      operated rats but only pSTAT-3 in TAC. AG in TAC significantly attenuated
      +dP/dt(max) (4,648 +/- 309 vs. 3,241 +/- 420 mmHg/s, IPC vs. IPC + AG, P < 0.05)
      and -dP/dt(min) (-2,239 +/- 205 vs. -1,323 +/- 85 mmHg/s, IPC vs. IPC + AG, P <
      0.05) and decreased only nuclear pSTAT-3. In myocardial hypertrophy, JAK-STAT
      signaling is important in IPC and exhibits a pattern of STAT activation distinct
      from nonhypertrophied myocardium. Limiting STAT-3 activation attenuates the
      efficacy of IPC in hypertrophy.

PMID- 16565303
TI  - Synergistic activation of salmon cardiac function by endothelin and beta
      adrenergic stimulation.
AB  - The aim was to find out the effects of endothelin-1 (ET-1) in salmon (Salmo
      salar) cardiac contractile and endocrine function and its possible interaction
      with beta-adrenergic regulation. We found that ET-1 has a positive inotropic
      effect in salmon heart. ET-1 (30 nM) increased the contraction amplitude 17+/
      4.7% compared with the basal level. beta-Adrenergic activation (isoprenaline, 100
      nM) increased contraction amplitude 30+/-13.1%, but it did not affect the
      contractile response to ET-1. ET-1 (10 nM) stimulated the secretion of salmon
      cardiac natriuretic peptide (sCP) from isolated salmon ventricle (3.3+/-0.14-fold
      compared with control) but did not have any effect on ventricular sCP mRNA.
      Isoprenaline alone (0.1-1,000 nM) did not stimulate sCP release, but ET-1 (10 nM)
      together with isoprenaline (0.1 nM) caused a significantly greater increase of
      sCP release than ET-1 alone (5.4+/-0.07 vs. 3.3+/-0.14 times increase compared
      with control). The effects on the contractile and secretory function could be
      inhibited by a selective ETA-receptor antagonist BQ-610 (1 microM), whereas ETB
      receptor blockage (by 100 nM BQ-788) enhanced the secretory response. Thus ET-1
      is a phylogenetically conserved regulator of cardiac function, which has
      synergistic action with beta-adrenergic stimulation. The modulatory effects of ET
      1 may therefore be especially important in situations with high beta-adrenergic
      tone.

PMID- 16565304
TI  - Immune complexes alter cerebral microvessel permeability: roles of complement and
      leukocyte adhesion.
AB  - Immune complexes (ICs) are potent inflammatory mediators in peripheral tissues.
      However, very few studies have examined the ability of ICs to induce inflammatory
      responses in the brain. Therefore, using preformed ICs or the reverse passive
      Arthus (RPA) model to localize ICs to the pial microvasculature of mice, we aimed
      to investigate the ability of ICs to induce an inflammatory response in the
      cerebral (pial) microvasculature. Application of preformed ICs immediately
      increased pial microvascular permeability, with a minimal change in leukocyte
      adhesion in pial postcapillary venules. In contrast, initiation of the RPA
      response in the pial microvasculature induced changes in cerebral microvascular
      permeability and increased leukocyte adhesion in pial postcapillary venules. The
      RPA response induced deposition of C3 in perivascular regions adjacent to sites
      of IC formation. Depletion of C3 abrogated RPA-induced microvascular permeability
      and leukocyte adhesion, indicating that the complement pathway was critical for
      this response. Inhibition of leukocyte adhesion via CD18 blockade also reduced IC
      induced microvascular permeability. However, this did not require intercellular
      adhesion molecule-1, inasmuch as blockade of intercellular adhesion molecule-1
      did not alter RPA-induced microvascular permeability and adhesion. These findings
      demonstrate that ICs are capable of rapidly inducing inflammatory responses in
      the cerebral microvasculature, with the complement pathway and leukocyte
      recruitment playing critical roles in microvascular dysfunction.

PMID- 16565305
TI  - Postnatal alterations in elastic fiber organization precede resistance artery
      narrowing in SHR.
AB  - Resistance artery narrowing and stiffening are key elements in the pathogenesis
      of essential hypertension, but their origin is not completely understood. In
      mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR),
      we have shown that inward remodeling is associated with abnormal elastic fiber
      organization, leading to smaller fenestrae in the internal elastic lamina. Our
      current aim is to determine whether this alteration is an early event that
      precedes vessel narrowing, or if elastic fiber reorganization in SHR arteries
      occurs because of the remodeling process itself. Using MRA from 10-day-old, 30
      day-old, and 6-mo-old SHR and normotensive Wistar Kyoto rats, we investigated the
      time course of the development of structural and mechanical alterations (pressure
      myography), elastic fiber organization (confocal microscopy), and amount of
      elastin (radioimmunoassay for desmosine) and collagen (picrosirius red). SHR MRA
      had an impairment of fenestrae enlargement during the first month of life. In 30
      day-old SHR, smaller fenestrae and more packed elastic fibers in the internal
      elastic lamina were paralleled by increased wall stiffness. Collagen and elastin
      levels were unaltered at this age. MRA from 6-mo-old SHR also had smaller
      fenestrae and a denser network of adventitial elastic fibers, accompanied by
      increased collagen content and vessel narrowing. At this age, elastase digestion
      was less effective in SHR MRA, suggesting a lower susceptibility of elastic
      fibers to enzymatic degradation. These data suggest that abnormal elastic fiber
      deposition in SHR increases resistance artery stiffness at an early age, which
      might participate in vessel narrowing later in life.

PMID- 16565306
TI  - Redistribution of connexin43 in regional acute ischemic myocardium: influence of
      ischemic preconditioning.
AB  - Connexins are known to play an essential role in the ischemic preconditioning
      (IP) of the heart; their functional role in this process, however, has not been
      clearly defined. For this reason, anesthetized rats were subjected to regional
      myocardial ischemia, with or without IP or reperfusion. In frozen sections of
      hearts, fluorescence immunohistochemical staining for connexin43 (Cx43) was
      performed. In contrast to undisturbed zones, tissue that had been subjected to
      ischemia revealed Cx43 immunostaining not only in the gap junctions but also in a
      conspicuous pattern in the free cellular membranes of the myocytes. In myocardium
      that was exposed to IP only, the ratio of immunofluorescence intensity in the
      free cellular membrane to that in the interior of the cell was 1.22 +/- 0.04
      (ratio in non-ischemia-exposed area = 1.04 +/- 0.01). When 15 or 45 min of
      permanent ischemia followed IP, the effect became more evident (ratio = 1.31 +/-
      0.03 and 1.46 +/- 0.03, respectively) and proved to be significantly greater than
      in the corresponding non-IP groups (ratio = 1.16 +/- 0.03 and 1.30 +/- 0.03,
      respectively, P < 0.01). Reperfusion led to an overall weakening of fluorescence
      intensities and a disappearance of the observed IP-specific differences. We
      conclude that IP initiates a redistribution of Cx43 from its natural position in
      the gap junctions toward the free plasma membrane, thereby improving the cell's
      chance of survival during the subsequent phase of prolonged ischemia by an
      unknown, supposedly gap junction-independent, mechanism.

PMID- 16565307
TI  - Relationship between changes in brachial artery flow-mediated dilation and basal
      release of nitric oxide in subjects with Type 2 diabetes.
AB  - Assessment of flow-mediated dilation (FMD) after forearm ischemia is widely used
      as a noninvasive bioassay of stimulated nitric oxide (NO)-mediated conduit artery
      vasodilator function in vivo. Whether this stimulated endothelial NO function
      reflects basal endothelial NO function is unknown. To test this hypothesis,
      retrospective analysis of randomized crossover studies was undertaken in 17
      subjects with Type 2 diabetes; 9 subjects undertook an exercise training or
      control period, whereas the remaining 8 subjects were administered an angiotensin
      II receptor blocker or placebo. FMD was assessed by using wall tracking of high
      resolution brachial artery ultrasound images in response to reactive hyperemia.
      Resistance vessel basal endothelium-dependent NO function was assessed by using
      intrabrachial administration of NG-monomethyl-L-arginine (L-NMMA) and
      plethysmographic assessment of forearm blood flow (FBF). FMD was higher after
      intervention compared with control/placebo (6.15+/-0.53 vs. 3.81+/-0.72%,
      P<0.001). There were no significant changes in the FBF responses to L-NMMA.
      Regression analysis between FMD and L-NMMA responses at entry to the study
      revealed an insignificant correlation (r=-0.10, P=0.7), and improvements in FMD
      with the interventions were not associated with changes in the L-NMMA responses
      (r=-0.04, P=0.9). We conclude that conduit artery-stimulated endothelial NO
      function (FMD) does not reflect basal resistance vessel endothelial NO function
      in subjects with Type 2 diabetes.

PMID- 16565308
TI  - Central and peripheral renin-angiotensin systems in ouabain-induced hypertension.
AB  - Chronic subcutaneous infusion of ouabain causes hypertension via central pathways
      involving angiotensin type 1 (AT(1)) receptor stimulation. The present study
      assessed plasma and tissue ANG I and II levels as well as AT1 receptor and
      angiotensin-converting enzyme (ACE) mRNA levels and binding densities by real
      time PCR and in vitro autoradiography in relevant brain nuclei and peripheral
      tissues (heart and kidney) in rats at 1 and/or 2 wk after start of ouabain
      infusion at 50 microg/day. After 2 wk (but not after 1 wk), blood pressures
      significantly increased (+15 mmHg). At 2 wk, plasma ANG I and II levels were
      markedly suppressed by ouabain. In contrast, in the heart and kidneys, ANG I
      levels were not affected, and ANG II levels tended to decrease, whereas in the
      hypothalamus ANG II content clearly increased. At 1 wk, no changes in ACE and AT1
      receptor densities were seen. After 2 wk, there were significant decreases in
      AT(1) receptor mRNA and densities in the organum vasculosum of the lamina
      terminalis (OVLT), subfornical organ (SFO), and paraventricular nucleus (PVN).
      ACE densities decreased only in the OVLT and SFO, but ACE mRNA showed more
      variable responses (decrease in OVLT vs. increase in PVN). In the kidneys, at 2
      wk both AT1 receptor and ACE densities were decreased, but mRNA abundance did not
      change. The heart showed no significant changes. The increase in hypothalamic ANG
      II content and associated decreases in central AT1 receptor and ACE densities
      support the involvement of the brain renin-angiotensin system in the central
      hypertensive mechanism of action of ouabain.

PMID- 16565309
TI  - Hyperinsulinemia: effect on cardiac mass/function, angiotensin II receptor
      expression, and insulin signaling pathways.
AB  - To investigate the association between hyperinsulinemia and cardiac hypertrophy,
      we treated rats with insulin for 7 wk and assessed effects on myocardial growth,
      vascularization, and fibrosis in relation to the expression of angiotensin II
      receptors (AT-R). We also characterized insulin signaling pathways believed to
      promote myocyte growth and interact with proliferative responses mediated by G
      protein-coupled receptors, and we assessed myocardial insulin receptor substrate
      1 (IRS-1) and p110 alpha catalytic and p85 regulatory subunits of
      phospatidylinositol 3 kinase (PI3K), Akt, MEK, ERK1/2, and S6 kinase-1 (S6K1).
      Left ventricular (LV) geometry and performance were evaluated
      echocardiographically. Insulin decreased AT1a-R mRNA expression but increased
      protein levels and increased AT2-R mRNA and protein levels and phosphorylation of
      IRS-1 (Ser374/Tyr989), MEK1/2 (Ser218/Ser222), ERK1/2 (Thr202/Tyr204), S6K1
      (Thr421/Ser424/Thr389), Akt (Thr308/Thr308), and PI3K p110 alpha but not of p85
      (Tyr508). Insulin increased LV mass and relative wall thickness and reduced
      stroke volume and cardiac output. Histochemical examination demonstrated myocyte
      hypertrophy and increases in interstitial fibrosis. Metoprolol plus insulin
      prevented the increase in relative wall thickness, decreased fibrosis, increased
      LV mass, and improved function seen with insulin alone. Thus our data demonstrate
      that chronic hyperinsulinemia decreases AT1a-to-AT2 ratio and increases MEK
      ERK1/2 and S6K1 pathway activity related to hypertrophy. These changes might be
      crucial for increased cardiovascular growth and fibrosis and signs of impaired LV
      function.

PMID- 16565311
TI  - Erythropoietin affords additional cardioprotection to preconditioned hearts by
      enhanced phosphorylation of glycogen synthase kinase-3 beta.
AB  - The aim of this study was to determine whether erythropoietin (EPO) affords
      additional cardioprotection to the preconditioned myocardium by enhanced
      phosphorylation of Akt, STAT3, or glycogen synthase kinase-3beta (GSK-3 beta).
      Preconditioning (PC) with 5-min ischemia/5-min reperfusion and EPO (5,000 U/kg
      iv) reduced infarct size (as % of area at risk, %IS/AR) after 20-min ischemia in
      rat hearts in situ from 56.5 +/- 1.8% to 25.2 +/- 2.1% and to 36.2 +/- 2.8%,
      respectively. PC-induced protection was significantly inhibited by a protein
      kinase C inhibitor, chelerythrine (5 mg/kg), and slightly blunted by a
      phosphatidylinositol-3-kinase inhibitor, wortmannin (15 microg/kg). The opposite
      pattern of inhibition was observed for EPO-induced protection. The combination of
      PC and EPO further reduced %IS/AR to 8.9 +/- 1.9%, and this protection was
      inhibited by chelerythrine and wortmannin. The additive effects of PC and EPO on
      infarct size were mirrored by their effects on the level of phosphorylated GSK-3
      beta at 5 min after reperfusion but not their effects on the level of phospho-Akt
      or phospho-STAT3. To mimic phosphorylation-induced inhibition of GSK-3 beta
      activity, SB-216763 (SB), a GSK-3 beta inhibitor, was administered before
      ischemia or 5 min before reperfusion. Infarct size was significantly reduced by
      preischemic injection (%IS/AR = 40.4 +/- 2.2% by 0.6 mg/kg SB and 34.0 +/- 1.8%
      by 1.2 mg/kg SB) and also by prereperfusion injection (%IS/AR = 32.0 +/- 2.0% by
      1.2 mg/kg SB). These results suggest that EPO and PC afford additive infarct size
      limiting effects by additive phosphorylation of GSK-3beta at the time of
      reperfusion by Akt-dependent and -independent mechanisms.

PMID- 16565310
TI  - Calcium channel blockade prevents pressure-dependent inward remodeling in
      isolated subendocardial resistance vessels.
AB  - The capacity for myocardial perfusion depends on the structure of the coronary
      microvascular bed. Coronary microvessels may adapt their structure to various
      stimuli. We tested whether the local pressure profile affects tone and remodeling
      of porcine coronary microvessels. Subendocardial vessels (approximately 160
      microm, n=53) were cannulated and kept in organoid culture for 3 days under
      different transvascular pressure profiles: Osc 80: mean 80 mmHg, 60 mmHg peak
      peak sine wave pulsation amplitude at 1.5 Hz; St 80: steady 80 mmHg; Osc 40: mean
      40 mmHg, 30 mmHg amplitude; St 40: steady 40 mmHg. Under the Osc 80 profile,
      modest tone developed, reducing the diameter to 81+/-14% (mean+/-SE, n=6) of the
      maximal, passive diameter. No inward remodeling was found here, as determined
      from the passive pressure-diameter relation after 3 days of culture. Under all
      other profiles, much more tone developed (e.g., Osc 40: to 26+/-3%, n=7). In
      addition, these vessels showed eutrophic (i.e., without a change in wall cross
      sectional area) inward remodeling (e.g., Osc 40: passive diameter reduction by
      24+/-3%). The calcium blocker amlodipine induced maintained dilation in St 40
      vessels and reversed the 22+/-3% (n=6) inward remodeling to 15+/-3% (n=8) outward
      remodeling toward day 3. Vessels required a functional endothelium to maintain
      structural integrity in culture. Our data indicate that reduction of either mean
      pressure or pulse pressure leads to microvascular constriction followed by inward
      remodeling. These effects could be reversed by amlodipine. Although microvascular
      pressure profiles distal to stenoses are poorly defined, these data suggest that
      vasodilator therapy could improve subendocardial microvascular function and
      structure in coronary artery disease.

PMID- 16565312
TI  - Additive effects of combined blockade of AT1 receptor and HMG-CoA reductase on
      left ventricular remodeling in infarcted rats.
AB  - Both angiotensin receptor antagonists and 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG-CoA) reductase inhibitors have been shown to attenuate cardiomyocyte
      hypertrophy after myocardial infarction. Whether combination treatment may be
      superior to either drug alone on cardiomyocyte hypertrophy remains unclear. After
      ligation of the left anterior descending artery, rats were randomized to both,
      one, or neither of the angiotensin receptor antagonists olmesartan (0.01, 0.1, 1,
      and 2 mg.kg-1.day-1) and HMG-CoA reductase inhibitor pravastatin (5 mg.kg-1.day
      1) for 4 wk. Each drug, when given alone, decreased cardiomyocyte sizes isolated
      by enzymatic dissociation at the border zone when compared with vehicles.
      However, compared with either drug alone, combined olmesartan and pravastatin
      prevent cardiomyocyte hypertrophy to a larger extent, which was further confirmed
      by downregulation of the left ventricular atrial natriuretic peptide mRNA. The
      myocardial endothelin-1 levels at the border zone were 6.5-fold higher (P<0.0001)
      in the vehicle group compared with the sham group, which can be inhibited after
      pravastatin administration. Combination treatment significantly attenuated
      cardiomyocyte hypertrophy in a dose-dependent manner, although tissue endothelin
      1 levels remained stable in combination groups of different olmesartan doses.
      Measurements of the arrhythmic score mirrored those of cardiomyocyte hypertrophy.
      Dual therapy with pravastatin and olmesartan, which produced an additive
      reduction in cardiomyocyte hypertrophy and cardiac fibrosis after myocardial
      infarction through different mechanisms, decreases the propensity of the heart to
      arrhythmogenesis. Pravastatin administration provided favorable ventricular
      remodeling, probably through decreased tissue endothelin-1 level. In contrast,
      olmesartan-related attenuated cardiomyocyte hypertrophy is independent of
      endothelin-1 pathway.

PMID- 16565313
TI  - DNA damage is an early event in doxorubicin-induced cardiac myocyte death.
AB  - Anthracyclines are antitumor agents the main clinical limitation of which is
      cardiac toxicity. The mechanism of this cardiotoxicity is thought to be related
      to generation of oxidative stress, causing lethal injury to cardiac myocytes.
      Although protein and lipid oxidation have been documented in anthracycline
      treated cardiac myocytes, DNA damage has not been directly demonstrated. This
      study was undertaken to determine whether anthracyclines induce cardiac myocyte
      DNA damage and whether this damage is linked to a signaling pathway culminating
      in cell death. H9c2 cardiac myocytes were treated with the anthracycline
      doxorubicin at clinically relevant concentrations, and DNA damage was assessed
      using the alkaline comet assay. Doxorubicin induced DNA damage, as shown by a
      significant increase in the mean tail moment above control, an effect ameliorated
      by inclusion of a free radical scavenger. Repair of DNA damage was incomplete
      after doxorubicin treatment in contrast to the complete repair observed in H2O2
      treated myocytes after removal of the agent. Immunoblot analysis revealed that
      p53 activation occurred subsequent in time to DNA damage. By a fluorescent assay,
      doxorubicin induced loss of mitochondrial membrane potential after p53
      activation. Chemical inhibition of p53 prevented doxorubicin-induced cell death
      and loss of mitochondrial membrane potential without preventing DNA damage,
      indicating that DNA damage was proximal in the events leading from doxorubicin
      treatment to cardiac myocyte death. Specific doxorubicin-induced DNA lesions
      included oxidized pyrimidines and 8-hydroxyguanine. DNA damage therefore appears
      to play an important early role in anthracycline-induced lethal cardiac myocyte
      injury through a pathway involving p53 and the mitochondria.

PMID- 16565314
TI  - A new look at phospholamban in pressure-overload hypertrophy.

PMID- 16565315
TI  - Hypoxia-induced vascular smooth muscle relaxation: increased ATP-sensitive K+
      efflux or decreased voltage-sensitive Ca2+ influx?

PMID- 16565316
TI  - Heat shock-induced cardioprotection activates cytoskeletal-based cell survival
      pathways.
AB  - To define better the subcellular mechanism of heat shock (HS)-induced
      cardioprotection, we examined the effect of HS, as well as selective expression
      of individual HS proteins (HSPs), on cell injury in neonatal rat ventricular
      myocytes (NRVM). HS was induced in NRVM by a rapid elevation of temperature to 42
      degrees C for 20 min followed by 20-24 h of recovery at 37 degrees C. Other NRVM
      were infected with a replication-deficient adenovirus encoding HSP27 or HSP70. On
      the same day, all groups were subjected to metabolic inhibition (MI). Cell injury
      was assayed by measurement of the percentage of total lactate dehydrogenase
      released, the percentage of cells staining with trypan blue, or TdT-mediated dUTP
      nick-end labeling, whereas cell signaling was assayed by immunoblot analysis and
      coimmunoprecipitation. Before MI, the viability of all treated groups did not
      differ significantly from control NRVM. HS resulted in a significant increase in
      HSP70 and HSP27 expression. Infection with either virus caused a significant
      increase in selective HSP content compared with control NRVM. HS protected NRVM
      from injury. Selective expression of HSP27 or HSP70 alone was not protective in
      NRVM, but dual infection with both viral vectors (HSP27 + HSP70) was protective.
      HS and HSP27 + HSP70 expression caused increased paxillin localization in the
      membrane fraction, which persisted in response to MI, compared with control NRVM.
      HS increased the integrin-paxillin-focal adhesion kinase interaction, whereas
      targeted inhibition of focal adhesion kinase activity abolished the integrin
      paxillin association and resulted in an increase in cell death. HS and HSP27 +
      HSP70 expression increased the association of members of the focal adhesion
      complex and protected NRVM against irreversible injury. Cytoskeletal-based
      signaling pathways at focal adhesion junctions may represent a unique pathway of
      cardioprotection.

PMID- 16565318
TI  - Alternans and spiral breakup in a human ventricular tissue model.
AB  - Ventricular fibrillation (VF) is one of the main causes of death in the Western
      world. According to one hypothesis, the chaotic excitation dynamics during VF are
      the result of dynamical instabilities in action potential duration (APD) the
      occurrence of which requires that the slope of the APD restitution curve exceeds
      1. Other factors such as electrotonic coupling and cardiac memory also determine
      whether these instabilities can develop. In this paper we study the conditions
      for alternans and spiral breakup in human cardiac tissue. Therefore, we develop a
      new version of our human ventricular cell model, which is based on recent
      experimental measurements of human APD restitution and includes a more extensive
      description of intracellular calcium dynamics. We apply this model to study the
      conditions for electrical instability in single cells, for reentrant waves in a
      ring of cells, and for reentry in two-dimensional sheets of ventricular tissue.
      We show that an important determinant for the onset of instability is the
      recovery dynamics of the fast sodium current. Slower sodium current recovery
      leads to longer periods of spiral wave rotation and more gradual conduction
      velocity restitution, both of which suppress restitution-mediated instability. As
      a result, maximum restitution slopes considerably exceeding 1 (up to 1.5) may be
      necessary for electrical instability to occur. Although slopes necessary for the
      onset of instabilities found in our study exceed 1, they are within the range of
      experimentally measured slopes. Therefore, we conclude that steep APD restitution
      mediated instability is a potential mechanism for VF in the human heart.

PMID- 16565317
TI  - Differential effects of postconditioning on myocardial stunning and infarction: a
      study in conscious dogs and anesthetized rabbits.
AB  - Postconditioning, i.e., brief intermittent episodes of myocardial ischemia
      reperfusion performed at the onset of reperfusion, reduces infarct size after
      prolonged ischemia. Our goal was to determine whether postconditioning is
      protective against myocardial stunning. Accordingly, conscious chronically
      instrumented dogs (sonomicrometry, coronary balloon occluder) were subjected to a
      control sequence (10 min coronary artery occlusion, CAO, followed by coronary
      artery reperfusion, CAR) and a week apart to postconditioning with four cycles of
      brief CAR and CAO performed at completion of the 10 min CAO. Three
      postconditioning protocols were investigated, i.e., 15 s CAR/15 s CAO (n=5), 30 s
      CAR/30 s CAO (n=7), and 1 min CAR/1 min CAO (n=6). Left ventricular wall
      thickening was abolished during CAO and similarly reduced during subsequent
      stunning in control and postconditioning sequences (e.g., at 1 h CAR, 33+/-4 vs.
      34+/-4%, 30+/-4 vs. 30+/-4%, and 33+/-4 vs. 32+/-4% for 15 s postconditioning, 30
      s postconditioning, and 1 min postconditioning vs. corresponding control,
      respectively). We confirmed this result in anesthetized rabbits by demonstrating
      that shortening of left ventricular segment length was similarly depressed after
      10 min CAO in control and postconditioning sequences (4 cycles of 30 s CAR/30 s
      CAO). In additional rabbits, the same postconditioning protocol significantly
      reduced infarct size after 30 min CAO and 3 h CAR (39+/-7%, n=6 vs. 56+/-4%, n=7
      of the area at risk in postconditioning vs. control, respectively). Thus,
      contrasting to its beneficial effects on myocardial infarction, postconditioning
      does not protect against myocardial stunning in dogs and rabbits. Conversely,
      additional episodes of ischemia-reperfusion with postconditioning do not worsen
      myocardial stunning.

PMID- 16565319
TI  - Effect of simulated I(to) on guinea pig and canine ventricular action potential
      morphology.
AB  - The transient outward current (I(to)) is a major repolarizing current in the
      heart. Marked reduction of I(to) density occurs in heart failure and is
      accompanied by significant action potential duration (APD) prolongation. To
      understand the species-dependent role of I(to) in regulating the ventricular
      action potential morphology and duration, we introduced simulated I(to)
      conductance in guinea pig and canine endocardial ventricular myocytes using the
      dynamic clamp technique and perforated patch-clamp recordings. The effects of
      simulated I(to) in both types of cells were complex and biphasic, separated by a
      clear density threshold of approximately 40 pA/pF. Below this threshold,
      simulated I(to) resulted in a distinct phase 1 notch and had little effect on or
      moderately prolonged the APD. I(to) above the threshold resulted in all-or-none
      repolarization and precipitously reduced the APD. Qualitatively, these results
      agreed with our previous studies in canine ventricular cells using whole cell
      recordings. We conclude that 1) contrary to previous gene transfer studies
      involving the Kv4.3 current, the response of guinea pig ventricular myocytes to a
      fully inactivating I(to) is similar to that of canine ventricular cells and 2) in
      animals such as dogs that have a broad cardiac action potential, I(to) does not
      play a major role in setting the APD.

PMID- 16565320
TI  - In vivo stimulatory effect of erythropoietin on endothelial nitric oxide synthase
      in cerebral arteries.
AB  - The discovery of tissue protective effects of erythropoietin has stimulated
      significant interest in erythropoietin (Epo) as a novel therapeutic approach to
      vascular protection. The present study was designed to determine the cerebral
      vascular effects of recombinant Epo in vivo. Recombinant adenoviral vectors
      (10(9) plaque-forming units/animal) encoding genes for human erythropoietin
      (AdEpo) and beta-galactosidase (AdLacZ) were injected into the cisterna magna of
      rabbits. After 48 h, basilar arteries were harvested for analysis of vasomotor
      function, Western blotting, and measurement of cGMP levels. Gene transfer of
      AdEpo increased the expressions of recombinant Epo and its receptor in the
      basilar arteries. Arteries exposed to recombinant Epo demonstrated attenuation of
      contractile responses to histamine (10(-9) to 10(-5) mol/l) (P < 0.05, n = 5).
      Endothelium-dependent relaxations to acetylcholine (10(-9) to 10(-5) mol/l) were
      significantly augmented (P < 0.05, n = 5), whereas endothelium-independent
      relaxations to a nitric oxide (NO) donor 2-(N,N-diethylamino)diazenolate-2-oxide
      sodium salt remained unchanged in AdEpo-transduced basilar arteries. Transduction
      with AdEpo increased the protein expression of endothelial NO synthase (eNOS) and
      phosphorylated the S1177 form of the enzyme. Basal levels of cGMP were
      significantly elevated in arteries transduced with AdEpo consistent with
      increased NO production. Our studies suggest that in cerebral circulation, Epo
      enhances endothelium-dependent vasodilatation mediated by NO. This effect could
      play an important role in the vascular protective effect of Epo.

PMID- 16565321
TI  - Postganglionic nerve stimulation induces temporal inhibition of excitability in
      rabbit sinoatrial node.
AB  - Vagal stimulation results in complex changes of pacemaker excitability in the
      sinoatrial node (SAN). To investigate the vagal effects in the rabbit SAN, we
      used optical mapping, which is the only technology that allows resolving
      simultaneous changes in the activation pattern and action potentials
      morphologies. With the use of immunolabeling, we identified the SAN as a
      neurofilament 160-positive but connexin 43-negative region (n = 5). Normal
      excitation originated in the SAN center with a cycle length (CL) of 405 +/- 14 ms
      (n = 14), spread anisotropically along the crista terminalis (CT), and failed to
      conduct toward the septum. Postganglionic nerve stimulation (PNS, 400-800 ms)
      reduced CL by 74 +/- 7% transiently and shifted the leading pacemaker inferiorly
      (78%) or superiorly (22%) from the SAN center by 2-10 mm. In the intercaval
      region between the SAN center and the septal block zone, PNS produced an 8 +/- 1
      mm(2) region of transient hyperpolarization and inexcitability. The first
      spontaneous or paced excitation following PNS could not enter this region for 500
      1,500 ms. Immunolabeling revealed that the PNS-induced inexcitable region is
      located between the SAN center and the block zone and has a 2.5-fold higher
      density of choline acetyltransferase than CT but is threefold lower than the SAN
      center. The fact that the inexcitability region does not coincide with the most
      innervated area indicates that the properties of the myocytes themselves, as well
      as intercellular coupling, must play a role in the inexcitability induction.
      Optically mapping revealed that PNS resulted in transient loss of pacemaker cell
      excitability and unidirectional entrance conduction block in the periphery of
      SAN.

PMID- 16565322
TI  - RGS1 and RGS13 mRNA silencing in a human B lymphoma line enhances responsiveness
      to chemoattractants and impairs desensitization.
AB  - Chemokines bind receptors that are members of the G-protein-coupled receptor
      family. Chemokine receptors transduce intracellular signals by activating
      heterotrimeric G-proteins. Acting to limit and modulate heterotrimeric G-protein
      signaling is a family of proteins, termed regulator of G-protein signaling (RGS).
      Two of these proteins, RGS1 and RGS13, are well-expressed in germinal center B
      cells and many Burkitt's lymphoma cell lines. Reducing RGS13 and to a lesser
      extent RGS1 expression in a Burkitt's lymphoma cell line enhances responsiveness
      to two chemokines, CXC chemokine ligand 12 (CXCL12) and CXCL13, and reducing both
      mRNAs augments the responses more dramatically. The double knock-down (KD) cells
      respond better to restimulation with CXCL12 or CXCL13 after a primary stimulation
      with CXCL12 than do the control cells. The double-KD cells also exhibit a greater
      propensity to polarize and to develop multiple small lamellipodia. These results
      indicate that RGS1 and RGS13 act together to regulate chemokine receptor
      signaling in human germinal center B lymphocytes and provide evidence that they
      contribute significantly to the rapid desensitization of the signaling pathway.

PMID- 16565323
TI  - Wnt signaling regulates transendothelial migration of monocytes.
AB  - The Wnt-signaling pathway plays a critical role in directing cell fate during
      embryogenesis. Several lines of evidence also suggest a role in inflammatory
      processes. Here, we analyzed whether Wnt signaling plays a role in leukocyte
      inflammatory responses. Monocytes from healthy donors expressed different
      Frizzled receptors, which are ligands for the Wnt molecules. Activation of the
      Wnt/beta-catenin pathway by LiCl or Wnt3a increased beta-catenin protein levels
      in monocytes but not in granulocytes. It is interesting that the activation of
      Wnt/beta-catenin signaling via Wnt3a in monocytes resulted in a decrease in
      migration through an endothelial layer (human dermal microvascular endothelial
      cell-1). Further experiments revealed that the decrease in transendothelial
      migration was associated with specific monocyte adherence to endothelial cells
      after Wnt exposure. The specificity was verified by a lack of Wnt3a-induced
      adhesion to fibronectin, laminin, or collagen compared with endothelial
      interaction. Analysis of the distribution of beta-catenin revealed a Wnt3a
      induced increase of beta-catenin in the cytoplasm. Wnt3a exposure did not result
      in any activation of the classical Wnt-target gene c-myc or a Wnt-target gene
      involved in cell adhesion (Connexin43). Our study implicates for the first time a
      role of canonical Wnt signaling in inflammatory processes in monocytes.

PMID- 16565324
TI  - In vivo CD40 ligation can induce T-cell-independent antitumor effects that
      involve macrophages.
AB  - We have previously demonstrated T cell-independent antitumor and antimetastatic
      effects of CD40 ligation that involved natural killer (NK) cells. As CD40
      molecules are expressed on the surface of macrophages (Mphi), we hypothesized
      that Mphi may also serve as antitumor effector cells when activated by CD40
      ligation. Progression of subcutaneous NXS2 murine neuroblastomas was delayed
      significantly by agonistic CD40 monoclonal antibody (anti-CD40 mAb) therapy in
      immunocompetent A/J mice, as well as in T and B cell-deficient severe combined
      immunodeficiency (SCID) mice. Although NK cells can be activated by anti-CD40
      mAb, anti-CD40 mAb treatment also induced a significant antitumor effect in
      SCID/beige mice in the absence of T and NK effector cells, even when noncytolytic
      NK cells and polymorphonuclear cells (PMN) were depleted. Furthermore, in vivo
      treatment with anti-CD40 mAb resulted in enhanced expression of cytokines and
      cell surface activation markers, as well as Mphi-mediated tumor inhibition in A/J
      mice, C57BL/6 mice, and SCID/beige mice, as measured in vitro. A role for Mphi
      was shown by reduction in the antitumor effect of anti-CD40 mAb when Mphi
      functions were inhibited in vivo by silica. In addition, activation of peritoneal
      Mphi by anti-CD40 mAb resulted in survival benefits in mice bearing
      intraperitoneal tumors. Taken together, our results show that anti-CD40 mAb
      immunotherapy of mice can inhibit tumor growth in the absence of T cells, NK
      cells, and PMN through the involvement of activated Mphi.

PMID- 16565326
TI  - Exotic disease contingency plan for Wales.

PMID- 16565327
TI  - Veterinary medicines regulations: VMD proposes "minor" changes for 2006.

PMID- 16565329
TI  - Strategies for controlling FMD.

PMID- 16565325
TI  - Emerging roles for ectodomain shedding in the regulation of inflammatory
      responses.
AB  - The multistep model of leukocyte recruitment to sites of inflammation has helped
      elucidate specific molecular cues for each of the individual steps. However, it
      is less clear how cells transition between the different steps and how the
      complex interactions are coordinately regulated. Once a leukocyte sticks to the
      endothelium, it only takes a few minutes to reach the subendothelial basement
      membrane, so the transitions and regulatory mechanisms must be rapid. We put
      forward the hypothesis that proteolytic shedding of cell surface proteins
      provides a mechanism to aid in the rapid transition of cells and coordinate the
      complex, multistep process of leukocyte recruitment in response to inflammatory
      stimuli. Support for this hypothesis is provided from analyses of disease states
      and from studies with protease inhibitors and genetically engineered mutations
      that prevent "ectodomain shedding" of cell surface proteins and consequently
      perturb the inflammatory response.

PMID- 16565332
TI  - Eradication of bovine TB: learning from other countries.

PMID- 16565335
TI  - Equine disease surveillance, October to December 2005.

PMID- 16565337
TI  - Evidence for the presence of bluetongue virus in Kosovo between 2001 and 2004.
AB  - In 2001, clinical cases of bluetongue were observed in Kosovo, and in that year
      and in 2003 and 2004, serum samples were collected from cattle and small
      ruminants and tested for antibodies to bluetongue virus. The results provide
      evidence that bluetongue virus was not present in Kosovo before the summer of
      2001, but that the virus circulated subclinically among the cattle and sheep
      populations of Kosovo in 2002, 2003 and 2004.

PMID- 16565338
TI  - Mortality of Swedish horses with complete life insurance between 1997 and 2000:
      variations with sex, age, breed and diagnosis.
AB  - The aim of this study was to evaluate the potential usefulness of the database
      maintained by the Swedish insurance company Agria for providing mortality
      statistics on Swedish horses. Mortality statistics (incidence rates and survival)
      were calculated, both crudely and stratified by sex, age, breed, breed group and
      diagnosis, for the horses with complete life insurance, which covers most health
      problems. The total mortality was 415 (95 per cent confidence interval [CI] 399
      to 432) deaths per 10,000 horse-years at risk, and the diagnostic mortality,
      including only deaths with an assigned diagnosis, was 370 (95 per cent CI 355 to
      386) deaths per 10,000 horse-years at risk. The diagnostic mortality of geldings
      was 459 (95 per cent CI 431 to 487), of mares 345 (95 per cent CI 322 to 365) and
      of stallions 214 (95 per cent CI 182 to 247) deaths per 10,000 horse-years at
      risk. The mortality rates increased with age and differed widely between breeds.
      Survival analysis showed that the median age at death of the horses enrolled
      before they were one year of age was 18.8 years. The most common cause of death
      or euthanasia was joint problems, which were responsible for 140 (95 per cent CI
      130 to 149) deaths per 10,000 horse-years at risk. The results of multivariable
      models developed by using Poisson regression generally agreed well with the crude
      results.

PMID- 16565339
TI  - Endoscopic examination of snakes by access through an air sac.
AB  - Sixteen boa constrictors (Boa constrictor), three royal pythons (Python regius)
      and 15 Burmese pythons (Python molurus bivittatus) were examined endoscopically
      by access through the air sac. The snakes were immobilised in a ventral position
      using a half-open anaesthetic system with assisted ventilation and a mixture of
      isoflurane and oxygen. The rigid endoscope was introduced percutaneously and the
      internal structure of the lungs and the air sac, and the shape, size and external
      surface of the liver were visible in the cranial direction. In the smaller snakes
      the bifurcation and caudal part of the trachea could be viewed, provided the
      endoscope was positioned in a retrograde orientation. The caudal orientation of
      the endoscope made it possible to view the gall bladder and the size, shape and
      surface of the spleen. In some cases, the pancreas and the surface of the stomach
      and colon could be monitored. Endoscopy through the air sac also made it possible
      to check the major veins in the coelom. The snakes were monitored for at least 30
      days after the intervention and no changes in their respiratory function or
      general health were observed.

PMID- 16565340
TI  - Facial myokymia in a puppy.

PMID- 16565342
TI  - Production of 24 transferable embryos in one flush by a Garole microsheep.

PMID- 16565341
TI  - Ichthyosis in Chianina cattle.

PMID- 16565343
TI  - Premovement testing of cattle.

PMID- 16565345
TI  - Bovine tuberculosis in cats.

PMID- 16565344
TI  - TB policy and the badger culling trials.

PMID- 16565346
TI  - Repetitive facial nerve stimulation in a cow.

PMID- 16565347
TI  - Dystocia in immature heifers.

PMID- 16565348
TI  - Do pigs suffer allergic reactions to straw?

PMID- 16565349
TI  - Ischemia induces aggravation of baseline repolarization abnormalities in left
      ventricular hypertrophy: a deleterious interaction.
AB  - Epidemiological studies show that left ventricular hypertrophy (LVH) and
      hypertension (HT) in coronary artery disease increases the risk for
      cardiovascular events including sudden cardiac death (SCD). According to
      experimental studies, myocardial hypertrophy is associated both with altered
      electrophysiological properties (including prolonged repolarization) and
      increased vulnerability to ischemia. However, human data to support a
      repolarization-related mechanism for the increased SCD risk has not been
      provided. We therefore studied 187 patients undergoing three-dimensional
      vectorcardiographic monitoring during coronary angioplasty. Eight parameters
      reflecting different aspects of ventricular repolarization were used: 1) the ST
      segment (ST-VM and STC-VM), 2) the T vector (QRS-T angle, Televation, and
      Tazimuth), and 3) the T vector loop (Tavplan, Teigenv, and Tarea). Data
      collection was performed at rest and at the time of maximum ischemia during
      coronary occlusion. The patients were divided into three groups: 33 patients with
      ECG signs of LVH (18 with HT), 54 with HT but without LVH signs, and 100 patients
      with neither. Coronary artery disease patients with LVH not only had the most
      abnormal baseline repolarization (as expected) but also a significantly more
      pronounced repolarization response during coronary occlusion, whereas HT patients
      had mean parameter values between LVH patients and those without neither HT nor
      LVH signs. Because there is a relation between increased SCD risk and
      repolarization disturbances in various clinical settings, the results of the
      present study are in agreement with animal data and epidemiological observations,
      although other factors than disturbed repolarization might be of importance.

PMID- 16565350
TI  - Porcine cardiac myocyte power output is increased after chronic exercise
      training.
AB  - Chronic exercise training increases the functional capacity of the heart, perhaps
      by increased myocyte contractile function, as has been observed in rodent
      exercise models. We examined whether cardiac myocyte function is enhanced after
      chronic exercise training in Yucatan miniature swine, whose heart characteristics
      are similar to humans. Animals were designated as either sedentary (Sed), i.e.,
      cage confined, or exercise trained (Ex), i.e., underwent 16-20 wk of progressive
      treadmill training. Exercise training efficacy was shown with significantly
      increased heart weight-to-body weight ratios, skeletal muscle citrate synthase
      activity, and exercise tolerance. Force-velocity properties were measured by
      attaching skinned cardiac myocytes between a force transducer and position motor,
      and shortening velocities were measured over a range of loads during maximal Ca2+
      activation. Myocytes (n = 9) from nine Ex pigs had comparable force production
      but a approximately 30% increase in peak power output compared with myocytes (n =
      8) from eight Sed. Interestingly, Ex myofibrillar samples also had higher
      baseline PKA-induced phosphorylation levels of cardiac troponin I, which may
      contribute to the increase in power. Overall, these results suggest that enhanced
      power-generating capacity of porcine cardiac myofibrils contributes to improved
      cardiac function after chronic exercise training.

PMID- 16565351
TI  - Point:Counterpoint authors respond to commentaries on "Supraspinal locomotor
      centers do/do not contribute significantly to the hyperpnea of dynamic exercise
      in humans".

PMID- 16565352
TI  - Components and mechanisms of thermal hyperpnea.
AB  - The pattern of breathing during a hyperthermia-induced hyperventilation varies
      across different species. Thermal tachypnea is a first phase panting response
      adopted during hyperthermia when tidal volume is minimized and the frequency of
      breathing is maximized. Blood-gas tensions and pH are maintained during this
      hyperventilation, and the associated heat loss helps the animal regulate its body
      temperature. A second pattern of breathing adopted in hyperthermia is thermal
      hyperpnea; this response is the focus of this review. This form of
      hyperventilation is evident after an increase in core temperature and it is
      apparent in humans. Increases of tidal volume as well as frequency of breathing
      are evident during this response that results in a respiratory alkalosis. The
      cause of thermal hyperpnea is not resolved; evidence of the potential mechanisms
      underlying this response support that modulators of the response act in either a
      multiplicative or additive manner with body temperatures. The details of the
      designs and methodologies of the studies supporting or refuting these two views
      are discussed. A physiological rationale for thermal hyperpnea is presented in
      which it is suggested this response serves a heat-loss role and contributes to
      selective brain cooling in hyperthermic humans. Ongoing research in this area is
      focused on resolving the mechanisms underlying thermal hyperpnea and its
      contribution to cranial thermoregulation. The direct application of this research
      is for the care of febrile and hyperthermic patients.

PMID- 16565353
TI  - Time course and differential responses of the major heat shock protein families
      in human skeletal muscle following acute nondamaging treadmill exercise.
AB  - The exercise-induced expression of heat shock proteins (HSPs) in rodent models is
      relatively well defined. In contrast, comparable data from human studies are
      limited and the exercise-induced stress response of human skeletal muscle is far
      from understood. This study has characterized the time course and magnitude of
      the HSP response in the skeletal muscles of a healthy active, but untrained,
      young male population following a running exercise protocol. Eight subjects
      performed 45 min of treadmill running at a speed corresponding to their lactate
      threshold (11.7 +/- 0.5 km/h; 69.8 +/- 4.8% maximum O2 uptake). Muscle biopsies
      were obtained from the vastus lateralis muscle immediately before and at 24 h, 48
      h, 72 h, and 7 days postexercise. Exercise induced a significant (P < 0.05) but
      variable increase in HSP70, heat shock cognate (HSC) 70, and HSP60 expression
      with peak increases (typically occurring at 48 h postexercise) to 210, 170, and
      139% of preexercise levels, respectively. In contrast, exercise did not induce a
      significant increase in either HSP27, alphaB-crystallin, SOD 2 (MnSOD) protein
      content, or the activity of SOD and catalase. When examining baseline protein
      levels, HSC70, HSP27, and alphaB-crystallin appeared consistently expressed
      between subjects, whereas HSP70 and MnSOD displayed marked individual variation
      of up to 3- and 1.5-fold, respectively. These data are the first to define the
      time course and extent of HSP production in human skeletal muscle following a
      moderately demanding and nondamaging running exercise protocol. Data demonstrate
      a differential effect of aerobic exercise on specific HSPs.

PMID- 16565354
TI  - Low-intensity tensile loading increases intratendinous glucose uptake in the
      Achilles tendon.
AB  - The metabolic activity of tendinous tissues has traditionally been considered to
      be of limited magnitude. However, recent studies have suggested that glucose
      uptake increases in the force-transmitting tissues as a response to contractile
      loading, which in turn indicates an elevated tissue metabolism. The purpose of
      the present study was to investigate whether such a mechanism could be observed
      for the human Achilles tendon following tensile loading. Six subjects
      participated in the study. Unilateral Achilles tendon loading was applied by 25
      min intermittent voluntary plantar flexor contractions. A radioactive tracer
      ([18F]-2-fluoro-2-deoxy-D-glucose) was administered during muscle action, and
      glucose uptake was measured by use of PET. Regions of interest were defined on
      the PET images corresponding to the cross section of Achilles tendon at two
      longitudinally separated sites (insertion and free tendon). Glucose uptake index
      was determined within respective regions of interest for the active and resting
      leg. Tendon force during voluntary contractions was approximately 13% of maximal
      voluntary contraction force. Tendon loading induced an elevated glucose uptake
      index compared with that of the contralateral resting tendon in the region of
      tendon insertion (0.13 +/- 0.05 vs. 0.09 +/- 0.02; P < 0.05) and at the free
      tendon (0.12 +/- 0.01 vs. 0.08 +/- 0.02; P < 0.05). The present data suggest that
      tissue metabolism is elevated in the human Achilles tendon in response to low
      intensity loading.

PMID- 16565357
TI  - Immunohistochemical detection of multidrug-resistant protein expression in
      retinoblastoma treated by primary enucleation.
AB  - PURPOSE: To compare the expression of multidrug-resistant proteins in
      retinoblastoma tumors among eyes treated with primary enucleation. METHODS: A
      group of 18 patients with unilateral retinoblastoma with advanced intraocular
      disease was selected for the study. All patients had undergone primary
      enucleation. A histologic specimen from each patient was retrieved from the
      pathology archives and a tissue gene microarray was constructed (0.6 x 3-4 mm).
      Standard immunohistochemical techniques were used to study the tissue microarrays
      for the expression of the ATP-binding cassette (ABC) transporters: breast cancer
      resistance protein (BCRP; ABCG2), multidrug-resistant protein 1/P-glycoprotein
      (MDR1/Pgp; ABCB1), multidrug-resistant-associated protein 1 (MRP1; ABCC1), MRP2
      (ABCC2), and MRP4 (ABCC4). RESULTS: Of the 18 specimens retrieved, 16 had
      adequate tissue for study. MRP1 was expressed in 8 (50%) of 16 tumors, and MRP2
      was expressed in 5 (31%) of 16 tumors. MDR1/Pgp was found in 2 (12%) of 16
      retinoblastomas. MRP4 and BCRP were not detected in any of the tumors studied.
      CONCLUSIONS: The results show that multiple ABC transporters were present in a
      cohort of sporadic patients with unilateral retinoblastoma who underwent primary
      enucleation. Studies are planned of the expression of ABC transporters in eyes
      treated by chemotherapy and/or radiation as a comparison with this group.

PMID- 16565356
TI  - Anecortave acetate as single and adjuvant therapy in the treatment of retinal
      tumors of LH(BETA)T(AG) mice.
AB  - PURPOSE: To evaluate the tumor control efficacy of the antiangiogenic agent
      anecortave acetate as single and combined therapy, in retinal tumor reduction
      using the LH(BETA)T(AG) mouse model of retinoblastoma. METHODS: Group A: Ten-week
      old, LH(BETA)T(AG) mice received a single subconjunctival injection of anecortave
      acetate (1200, 600, 300, and 150 microg) delivered to right eyes only. Group B:
      Ten-week-old, LH(BETA)T(AG) mice received a single subconjunctival injection of
      anecortave acetate (600, 300, and 150 microg) delivered to right eyes only,
      either during a cycle of carboplatin (six subconjunctival deliveries) or after
      the completed cycle. Carboplatin was delivered at the subtherapeutic
      concentration of 62.5 microg. All animals were euthanatized at 16 weeks of age,
      and the eyes were examined histopathologically. RESULTS: A statistically
      significant reduction in tumor burden was detected after a single periocular
      injection of anecortave acetate. The reduction of tumor burden followed a U
      shaped dose-response curve. Tumor burden was significantly decreased when
      anecortave acetate and carboplatin were combined. However, varying doses and
      delivery schedule of these agents had significant impact on the effectiveness of
      the combined treatment. The most effective scheme was delivering a low dose (150
      300 microg) of anecortave acetate after a complete cycle of carboplatin.
      Histopathological evaluation showed no signs of retinal toxicity to anecortave
      acetate delivery alone or in combination with carboplatin. CONCLUSIONS:
      Anecortave acetate, as monotherapy or as adjuvant therapy, significantly
      controlled tumor burden in a murine model of retinoblastoma. Moreover, adjuvant
      therapy enabled the use of typically subtherapeutic carboplatin doses without
      decreasing efficacy of the therapy.

PMID- 16565358
TI  - Heterozygous and homozygous mutations in PITX3 in a large Lebanese family with
      posterior polar cataracts and neurodevelopmental abnormalities.
AB  - PURPOSE: The PITX3 gene, which codes for a homeobox bicoidlike transcription
      factor is responsible for dominant cataract and anterior segment mesenchymal
      dysgenesis in humans. In the current study, a family with autosomal dominant
      posterior polar cataract (PPC) and a PITX3 mutation that cosegregates with the
      disease was examined. Also studied were two siblings who were homozygous for the
      PITX3 mutation who had microphthalmia and significant neurologic impairment.
      METHODS: A genome-wide screen, linkage analysis in the PITX3 chromosomal region
      10q25, haplotype analysis, and sequencing of the PITX3 gene were performed on 28
      affected and 14 unaffected member of a three-generation Lebanese family. RESULTS:
      Genome-wide linkage analysis showed a lod score of 3.56 at theta = 0.00 on
      chromosome 10 at area q25. Analysis of the haplotypes and phenotypes confined the
      disease locus to a region on 10q25 between the markers D10S1239 and D10S1268. A
      candidate gene, PITX3, maps to that region. Sequencing of the PITX3 gene revealed
      a heterozygous G deletion mutation in 25 of the 42 family members. In addition,
      two siblings from a consanguineous marriage were found to be homozygous for the
      deletion. CONCLUSIONS: This is the first report of homozygous PITX3 mutations in
      humans. The phenotype in these individuals highlights the role of PITX3 in ocular
      and central nervous system (CNS) development.

PMID- 16565355
TI  - Toll-like receptors and the eye.

PMID- 16565359
TI  - Truncation mutation in HRG4 (UNC119) leads to mitochondrial ANT-1-mediated
      photoreceptor synaptic and retinal degeneration by apoptosis.
AB  - PURPOSE: To characterize the time course of apoptosis and degeneration in a
      transgenic mouse model of retinal degeneration based on truncated mutant HRG4; to
      investigate the nature of binding of the mutant HRG4 to its target, ADP
      ribosylation factor-like (ARL)2; to study its effects on the downstream molecules
      Binder-of-ARL2 (BART) and adenine nucleotide transporter (ANT)-1 and on the
      induction of apoptosis. METHODS: Saturation binding, microscopic morphometric,
      Western blot, immunofluorescence, and TUNEL analyses were used. RESULTS:
      Increased apoptosis did not occur until 20 months in the transgenic retina,
      consistent with the delayed-onset degeneration in this model. The truncated HRG4
      protein exhibited approximately threefold greater affinity for ARL2 than the wild
      type HRG4, likely resulting in nonfunctional sequestration of ARL2. A significant
      decrease in ARL2 was present by 20 months, accompanied by a 50% decrease in ANT-1
      in the photoreceptor synaptic mitochondria, with evidence of mitochondrial
      dysfunction. Preapoptotic degeneration in the photoreceptor synapse was
      demonstrated with cytochrome c release and caspase 3 activation within the
      synapse-without evidence of TUNEL-positive apoptosis in the photoreceptor cell
      body-indicating an initial event in the synapse leading to apoptosis. Caspase 3
      was activated in the accompanying secondary neuron, consistent with transsynaptic
      degeneration. CONCLUSIONS: The results support a novel mechanism of retinal
      degeneration in which preapoptotic degeneration starts in the photoreceptor
      synapse because of a deficiency in ANT-1 and spreads to the secondary neuron
      transsynaptically, followed by apoptosis and degeneration in the cell body of the
      photoreceptor.

PMID- 16565360
TI  - Disruption of the gene encoding the beta1-subunit of transducin in the Rd4/+
      mouse.
AB  - PURPOSE: The Rd4/+ mouse inherits an autosomal dominant retinal degeneration that
      cosegregates with a large inversion spanning nearly all of mouse chromosome 4
      (Chr 4). This inversion is homozygous lethal. The hypothesis for the study was
      that disruption of a gene at one of the two breakpoints in the Rd4 chromosome is
      responsible for the retinal degeneration. The purpose was to identify the
      disrupted gene. METHODS: Genotyping was performed by PCR and gel electrophoresis.
      The Rd4/+ phenotype was confirmed by ERG. Fluorescence in situ hybridization
      (FISH) analysis was performed with bacterial artificial chromosome (BAC) probes.
      Northern and quantitative PCR procedures were used to evaluate Gnb1 mRNA
      expression. Protein expression was measured by Western blot. RESULTS: To identify
      the Rd4 gene defect, the breakpoints were first localized with a testcross and
      the locus refined by using FISH. Genetic testcross data revealed that the
      inversion breakpoints are located within a few centimorgans of both the telomeric
      and centromeric ends of Chr 4. Initial FISH analysis showed the proximal
      breakpoint of the inversion to be in the centromere itself. Therefore, we focused
      on the distal breakpoint and found that it lies in the second intron of the gene
      Gnb1, coding for the transducin beta1-subunit (Tbeta1) protein that is directly
      involved in the response to light of rod photoreceptors. Before the beginning of
      retinal degeneration in Rd4/+ retina, the levels of Gnb1 mRNA and Tbeta1 protein
      are 50% of those in wild-type retina. CONCLUSIONS: The results suggest that
      disruption of the Gnb1 gene is responsible for Rd4 retinal disease.

PMID- 16565361
TI  - Ubiquitin-conjugating enzyme 3 delays human lens epithelial cells in metaphase.
AB  - PURPOSE: Ubc3/Cdc34 is a ubiquitin-conjugating enzyme (Ubc) with well established
      functions in the G1-to-S-phase transition. Expecting to find similar effects in
      human lens epithelial cells (HLECs), the authors explored roles for this
      ubiquitin-conjugating enzyme in regulation of the HLEC cycle. METHODS:
      Catalytically incompetent Ubc3 (C88S, L97S), wild-type (wt)Ubc3, and mutant
      (mt)Ubc2 (C93A) were expressed in HLECs, by using an adenoviral vector, and cell
      cycle progression was assessed. RESULTS: Expression of mt- and wtUbc3, but not
      empty virus or mtUbc2, delayed the cell cycle in metaphase, rather than the
      expected G1 phase. Expression of both Ubc3s also stabilized M-phase regulators,
      cyclin A, cyclin B, and securin. Thus, it appeared that the Ubc3 enzymes were
      playing roles different from canonical proteolytic functions in targeting G1/S
      regulators for degradation. We also directly investigated the effect of
      inhibiting the proteasome on the cell cycle of HLECs. When the proteasome
      inhibitor was added to S-phase cells, the M-phase regulators were stabilized, and
      the cells were arrested in the G2/M phase. In contrast, if the proteasome
      inhibitor was added before the cells entered the S phase, stabilization of the G1
      kinase inhibitors p21WAF and p27KIP was observed and the cells were arrested in
      the G1 phase. CONCLUSIONS: The ubiquitin-proteasome pathway is involved in
      regulation of transitions between all phases of the HLEC cycle. However, in
      contrast with previously described roles for Ubc3 in governing G1/S transitions,
      expression of Ubc3 delays the HLEC cycle in metaphase. The data suggest novel
      roles for Ubc3 that do not involve the transfer of ubiquitin in the M phase in
      the HLEC cell cycle.

PMID- 16565362
TI  - Effect of short-term, high-dose retinol on dark adaptation in aging and early age
      related maculopathy.
AB  - PURPOSE: To examine the effect of a short course of high-dose retinol (preformed
      vitamin A) on dark adaptation in older adults with normal retinal health or early
      age-related maculopathy (ARM). METHODS: The study design was a randomized, double
      masked, placebo-controlled experiment. Adults > or = 50 years of age whose fundus
      photographs for the eye to be tested psychophysically fell within steps 1 to 9 of
      the Age-Related Eye Disease Study (AREDS) Grading System were randomly assigned
      to a 30-day course of 50,000 IU oral retinol or a placebo. At baseline and 30-day
      follow-up, dark adaptation was tested and the Low Luminance Questionnaire (LLQ),
      an instrument for assessing difficulty with vision in reduced lighting, was
      administered. Primary outcomes of interest were rod- and cone-mediated parameters
      of dark adaptation, with scores on the LLQ's six subscales as secondary outcomes.
      RESULTS: The sample consisted of 104 participants with 52 each in the
      intervention and placebo groups. There were no group differences in baseline
      variables. At 30-days, the dark-adaptation parameters of cone time-constant, cone
      threshold, rod-cone break, and rod threshold did not differ. The retinol
      intervention group had significantly larger (i.e., steeper) rod slopes,
      indicating faster sensitivity recovery, than did the placebo group (P = 0.0419).
      There were no group differences in scores on the LLQ subscales driving, extreme
      lighting, emotional distress, general lighting, or peripheral vision. The retinol
      group had a higher score by five points on the mobility subscale compared with
      the placebo group (P = 0.0141). Those who had the most self-reported change on
      the mobility subscale at day 30 were more likely to have greater change in the
      speed of dark adaptation, as indicated by the rod slope parameter (r = 0.24, P =
      0.0141). CONCLUSIONS: A short-term, high-dose course of retinol increased the
      rate of rod-mediated dark adaptation in older adults who were in the early phases
      of ARM or were exhibiting normal retinal aging. These results are consistent with
      the hypothesis that depositions and other structural changes in the retinal
      pigment epithelium and Bruch's membrane in aging and early ARM cause a localized
      retinoid deficiency.

PMID- 16565363
TI  - Tear film, contact lens, and patient-related factors associated with contact lens
      related dry eye.
AB  - PURPOSE: To examine tear film, contact lens, medical, and patient-related factors
      associated with self-reported contact lens-related dry eye. METHODS: Four hundred
      fifteen contact lens wearers were recruited and enrolled in this phase of a
      larger cross-sectional study. A variety of tear film (e.g., interferometry,
      osmolality, phenol red thread, meibography, fluorescein, and lissamine green
      staining), contact lens (i.e., water content, refractive index, material), and
      patient-related (e.g., gender, sociodemographic, education, income, and medical
      health) factors were examined in relation to dry eye status. Univariate and
      multivariate logistic regression models were used to examine the relation between
      these tear film, contact lens, and patient-related factors associated with dry
      eye status. RESULTS: Of the 415 enrolled, the data from 360 were used in the
      analyses. The average age was 31.1 +/- 11.5 years, 245 (68%) participants were
      female, and 55.3% were classified as having-contact lens-related dry eye via self
      report. Overall, 327 (90.8%) were hydrogel lens wearers and 33 (9.2%) were gas
      permeable lens wearers. Several factors were shown to be related to dry eye
      status in multivariate modeling, including female gender (P = 0.007), lenses with
      higher nominal water content (P = 0.002), rapid prelens tear film thinning time
      (P = 0.008), frequent usage of over-the-counter pain medication (P = 0.02),
      limbal injection (P = 0.03), and increased tear film osmolality (P = 0.05).
      CONCLUSIONS: Contact lens-related dry eye may be explained mechanistically by
      increased tear film thinning times (evaporation or dewetting) resulting in
      increased tear film osmolality. Other contributing factors include the use of
      high-water-content lenses, which have traditionally been reported to be
      associated with less patient comfort than lower-water-content lenses, potentially
      due to spoilation and deposition. As found in other studies of dry eye, women are
      more likely to report contact lens-related dry eye than are men.

PMID- 16565364
TI  - Asymmetry of retinal arteriolar branch widths at junctions affects ability of
      formulae to predict trunk arteriolar widths.
AB  - PURPOSE: To describe a revised formula for the estimation of retinal trunk
      arteriole widths from their respective arteriolar branch widths that improves the
      summarizing of retinal arteriolar diameters. METHODS: A group of young, healthy
      individuals underwent retinal photography and arteriolar and venular branching
      points were identified. Vessel widths of the vessel trunks and their branches
      were determined. The relationship between the branching coefficient (BC; quotient
      of the area of the branch and trunk vessels) and the asymmetry index (AI) of the
      vessel branches was explored. The result was used to formulate a new BC. To test
      the new BC, a second group of young, healthy individuals also underwent retinal
      photography. Arteriolar branching points were identified, and the trunk and
      branch arteriolar widths were recorded. This "revised" BC was compared against
      the gold standard of the BC as a constant value (1.28), as well as a theoretical
      formula for the BC that includes the angle between the two vessel branches.
      RESULTS: The BC of arterioles (but not venules) related to the AI (R = 0.275, P =
      0.0001; BC arterioles = 0.78 +/- 0.63 . AI). In the second group, the mean
      arteriolar trunk diameter was 15.56 pixels. The linear regression model for the
      arteriolar BC was superior to the BC constant of 1.28 (mean difference between
      estimated and calculated trunk vessel width was 2.16 vs. 2.23 pixels,
      respectively). The model based on the angle between the branch arterioles was the
      least accurate (3.43 pixels). CONCLUSIONS: A revised formula has been devised for
      the arteriolar BC using a linear regression model that incorporates its
      relationship to the AI. Further studies using this refined formula to calculate
      the BC are needed to determine whether it improves the ability to detect smaller
      associations between the retinal vascular network and cardiovascular disease.

PMID- 16565365
TI  - Influence of pupil diameter on the relation between ocular higher-order
      aberration and contrast sensitivity after laser in situ keratomileusis.
AB  - PURPOSE: To investigate the influence of pupil diameter on the relation between
      induced changes in ocular higher-order wavefront aberrations and changes in
      contrast sensitivity by conventional laser in situ keratomileusis (LASIK) for
      myopia. METHODS: In 215 eyes of 117 patients (age, 33.2 +/- 8.3 years) undergoing
      LASIK for myopia of -1.25 to -13.5 D (-5.28 +/- 2.55 D), ocular wavefront
      aberrations and contrast sensitivity function were determined before and 1 month
      after surgery. Preoperative photopic pupil diameter was measured with a digital
      camera. Ocular higher-order aberrations were measured for a 4-mm pupil with a
      Hartmann-Shack wavefront analyzer. The root-mean-square (RMS) of the third- and
      fourth-order Zernike coefficients was used to represent coma- and spherical-like
      aberration, respectively. From the contrast-sensitivity data, the area under the
      log contrast sensitivity function (AULCSF) was calculated. RESULTS: One hundred
      five eyes had a photopic pupil diameter of 4 mm or larger, and the remaining 110
      had a photopic pupil diameter smaller than 4 mm. There were no statistically
      significant differences in the background clinical data between these two groups.
      In the eyes with a photopic pupil diameter of 4 mm or larger, the changes in
      third-order comalike aberrations did not correlate with the changes in AULCSF
      (Pearson correlation coefficient, r = -0.037, P = 0.723) and 10% low-contrast
      visual acuity (r = 0.125, P = 0.224), but fourth-order spherical-like aberrations
      correlated significantly with the changes in AULCSF (r = -0.229, P = 0.024) and
      10% low-contrast visual acuity (r = 0.221, P = 0.038). In the eyes with photopic
      pupil size smaller than 4 mm, there were significant correlations between the
      changes in comalike aberrations and the changes in AULCSF (r = -0.487, P < 0.001)
      and 10% low-contrast visual acuity (r = 0.310, P = 0.003), but spherical-like
      aberrations showed no correlation with the changes in AULCSF (r = -0.078, P =
      0.485) and 10% low-contrast visual acuity (r = 0.208, P = 0.158). CONCLUSIONS: In
      eyes with larger photopic pupil diameter, increases in spherical-like aberration
      dominantly affect contrast sensitivity, whereas in eyes with smaller pupil size,
      changes in coma-like aberration exert greater influence on visual performance.

PMID- 16565366
TI  - Experimental study of the survival of metastatic cancer cells in corneal organ
      culture.
AB  - PURPOSE: Transmission of donor malignancy to the recipient could be one of the
      most disastrous complications of corneal grafting. Because of the scarcity of
      donor tissue and the lack of sufficient scientific evidence, the harvest of donor
      tissues from deaths due to systemic malignancy is permitted. This study was
      conducted to investigate the possible transmission of donor metastatic disease
      via corneal tissue preserved in organ culture (OC) conditions. METHODS: The
      viability of four frequent human cancer cell lines (lung, breast, skin, and
      colon) was studied in OC. Various inoculums of cancer cells labeled with the
      membrane marker PKH67 were seeded on donor corneas and preserved in OC, followed
      by cell-tracking studies, histopathology, and immunohistochemistry. HLA matching
      of the dissected Descemet's membrane (DM) of preserved corneas was conducted, to
      demonstrate cell adherence. Primary cell culture was performed to confirm the
      viability of adherent tumor cells. RESULTS: Viability tests showed a poor but
      persistent survival of cancer cells after 2 weeks in OC. Cell tracking,
      histopathology, and immunohistochemistry demonstrated cancer cell adherence to
      donor endothelium. HLA typing of the DM of preserved corneas revealed the
      presence of cancer cell alleles. Primary culture of the DM showed cell
      proliferation that was identical with the original cancer cell line, according to
      HLA studies. CONCLUSIONS: The findings demonstrate that under laboratory
      conditions, metastatic cancer cells adhere to donor corneal tissue, survive, and
      retain proliferative capacity during storage in OC. Cell lines differ in their
      viability potential, as well as the pattern of adherence to donor endothelium.
      Further in vivo experimentation in laboratory animals is need to determine the
      safety of such harvests.

PMID- 16565367
TI  - Mapping the corneal sub-basal nerve plexus in keratoconus by in vivo laser
      scanning confocal microscopy.
AB  - PURPOSE: To produce a two-dimensional reconstruction map of the living corneal
      sub-basal nerve plexus in keratoconus with in vivo confocal microscopy. METHODS:
      Four eyes of four subjects with keratoconus were examined by slit lamp
      biomicroscopy, Orbscan II slit-scanning elevation topography (Bausch & Lomb
      Surgical, Rochester, NY), and laser scanning in vivo confocal microscopy with the
      Heidelberg Retina Tomograph II, Rostock Corneal Module (Heidelberg Engineering,
      Heidelberg, Germany). Subjects were asked to fixate on targets arranged in a grid
      to enable in vivo confocal microscopy of the cornea in a wide range of positions.
      RESULTS: A mean of 402 +/- 57 images were obtained for each cornea, to create
      confluent montages. The mean dimensions of the corneal areas mapped were 6.60 +/-
      0.70 mm horizontally and 5.91 +/- 0.72 mm vertically. All corneas exhibited
      abnormal sub-basal nerve architecture compared with patterns previously observed
      in normal corneas. At the apex of the cone, a tortuous network of nerve fiber
      bundles was noted, many of which formed closed loops. At the topographic base of
      the cone, nerve fiber bundles appeared to follow the contour of the base, with
      many of the bundles running concentrically in this region. Central sub-basal
      nerve density was significantly lower in keratoconus corneas (10,478 +/- 2,188
      microm/mm2) compared with normal corneas (21,668 +/- 1,411 microm/mm2; Mann
      Whitney; P < 0.01). CONCLUSIONS: This is the first study to elucidate the overall
      distribution of sub-basal nerves in the living central to midperipheral human
      cornea in keratoconus, using laser scanning in vivo confocal microscopy.

PMID- 16565368
TI  - Unique distribution of thrombospondin-1 in human ocular surface epithelium.
AB  - PURPOSE: The study was conducted to elucidate the detailed expression pattern of
      angiogenesis-related factors in human ocular surface epithelium. The focus was
      factors with significantly higher gene expression in corneal epithelium (CE) than
      in conjunctival epithelium (CJE). METHODS: The relative gene expression of 36
      angiogenesis-related factors was compared in human CE and CJE, by using the
      introduced amplified fragment-length polymorphism (iAFLP) METHOD: Also examined
      were the expression patterns in the CE, limbal epithelium (LE), and CJE of
      factors with significantly higher expression in the CE, by using real-time PCR,
      in situ hybridization, immunohistochemistry, and immunoelectron microscopy.
      RESULTS: Only thrombospondin (TSP)-1 exhibited significantly higher expression in
      the CE. In situ hybridization and real-time PCR showed TSP-1 transcripts in the
      basal cells of the CE and LE. Compared with the CJE, they were significantly
      upregulated at those sites. Immunohistochemistry revealed that TSP-1 was strongly
      expressed in the basal region of the CE. Its expression was faint in LE and
      absent in CJE. Immunoelectron microscopy revealed that the CE and LE demonstrated
      TSP-1 labeling just below the epithelium, in the basal region of basal cells, and
      occasionally in the basal cell membrane. There was little or no labeling in the
      CJE. CONCLUSIONS: In the human ocular surface epithelium, basal cells of the CE
      and LE, but not of the CJE, synthesize TSP-1. High levels of TSP-1 are present
      only just below the CE. Its unique distribution may be related to corneal
      avascularity and integrity.

PMID- 16565369
TI  - Clusters of corneal epithelial cells reside ectopically in human conjunctival
      epithelium.
AB  - PURPOSE: The ocular surface is covered by two biologically distinct epithelia:
      corneal and conjunctival. The expression of keratin12 (K12) is currently
      considered a hallmark of cornea-type differentiation. In the current study, the
      biological features of K12-positive cells in human bulbar conjunctival epithelium
      were examined. METHODS: Human conjunctival tissues were subjected to investigate
      the K12-positive cells in conjunctiva by immunostaining, in situ hybridization,
      Western blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR),
      and fluorescence-activated cell sorting (FACS). Gene expression profiling of
      these cells was performed with introduced amplified-fragment length polymorphism
      (iAFLP). To determine the presence of stem- or progenitor cells, immunostaining
      and colony-forming assays were performed. RESULTS: Western blot analysis, RT-PCR
      revealed that K12 was expressed in conjunctival epithelium. Immunostaining
      analysis showed that K12-positive cells reside mainly in clusters in conjunctival
      epithelium. FACS analysis showed that 0.2% to 1.7% of conjunctival epithelial
      cells collected from the inferior bulbar conjunctiva were K12 positive. iAFLP
      analysis revealed that the gene expression patterns of these cells were highly
      similar to that of corneal epithelial cells. p63 and ABCG2 were expressed beneath
      the K12-positive cells. Some colony-forming cells expressed K12. CONCLUSIONS: The
      K12-positive cells appear to be ectopically residing, self-maintaining corneal
      epithelial cells in the conjunctival epithelium.

PMID- 16565370
TI  - Interacting influences of pregnancy and corneal injury on rabbit lacrimal gland
      immunoarchitecture and function.
AB  - PURPOSE: Previous reports indicated that pregnancy and corneal injury (CI)
      trigger alterations of lacrimal gland (LG) growth factor expression and
      redistributions of lymphocytes from periductal foci to acini. The purpose of this
      study was to test our hypothesis that pregnancy would exacerbate the changes
      induced by CI. METHODS: Corneas were injured with scalpel blades, and, 2 weeks
      later, LGs were collected for immunocytochemistry and Western blot analysis.
      Lacrimal fluid was collected under basal- and pilocarpine-stimulated conditions
      for protein determination and Western blot analyses. RESULTS: There were
      significant increases of immunoreactivity for prolactin, TGF-beta1, and EGF in
      duct cells during pregnancy and after CI, most prominent in pregnant animals with
      CI. Pregnancy decreased baseline lacrimal fluid secretion, whereas CI did not
      have a noticeable effect; pregnancy and CI combined resulted in increased fluid
      production. Pregnancy and CI each increased pilocarpine-induced lacrimal fluid
      production, whereas protein concentrations were decreased. Prolactin, TGF-beta1,
      and EGF were detected in LG by Western blot analysis but were minimally
      detectable in lacrimal fluid. RTLA+ and CD18+ cells were redistributed from
      periductal to interacinar sites during pregnancy and after CI, most prominent in
      pregnant animals with CI. CONCLUSIONS: Like pregnancy, CI is associated with
      redistribution of immune cells from periductal to interacinar sites and enhanced
      immunoreactivity of prolactin, TGF-beta1, and EGF in ductal cells. Although
      baseline lacrimal fluid secretion varied, the glands of all three experimental
      groups produced significant amounts of fluid in response to pilocarpine, but
      protein concentrations were decreased.

PMID- 16565371
TI  - FGF-2-induced wound healing in corneal endothelial cells requires Cdc42
      activation and Rho inactivation through the phosphatidylinositol 3-kinase
      pathway.
AB  - PURPOSE: Acquisition of elongated cells with pseudopodia is observed when corneal
      endothelial cells (CECs) are simultaneously treated with basic fibroblast growth
      factor (FGF)-2 and RhoA inhibitors. This study was designed to determine whether
      these phenotypes are migratory and whether Cdc42 activation and RhoA inactivation
      are involved in cell migration. METHODS: A scratch-induced directional migration
      assay was used to measure migratory rates. Activation of Cdc42 was determined by
      GTP pull-down assay. Transfection was performed using constitutively active (ca)
      or dominant negative (dn) Rho guanosine triphosphatase (GTPase) vectors. RESULTS:
      Stimulation with basic FGF-2 alone resulted in a 43% recovery of the wound area,
      whereas CECs treated with FGF-2 and Y27632 (inhibitor of Rho-associated kinase)
      achieved an 84% recovery of the wound area with a fast migratory speed (0.72
      microm/min). The synergistic effects of FGF-2 and Y27632 were completely blocked
      by LY294002 (PI 3-kinase inhibitor). Under these conditions, activation of PI 3
      kinase and Cdc42 were observed in the migratory cells. The involvement of
      activated Cdc42 and inactivated Rho in endothelial migration was determined by
      transfecting CECs with ca- or dnRho GTPase vectors. A high migratory rate (0.52
      microm/min) was seen in CECs expressing caCdc42, whereas endothelial migration
      was completely inhibited in CECs expressing caRho. When cells expressing caCdc42
      were treated with FGF-2, migration reached the maximum rate (0.69 microm/min),
      similar to that observed in cells treated with FGF-2 and Y27632. CONCLUSIONS:
      These findings suggest that endothelial migration is induced by activated Cdc42
      and inactivated Rho via PI 3-kinase after FGF-2 stimulation and that Cdc42
      activation is crucial for CECs to acquire the characteristic migratory
      phenotypes.

PMID- 16565372
TI  - Replication competence and senescence in central and peripheral human corneal
      endothelium.
AB  - PURPOSE: To compare replication competence and senescence in human corneal
      endothelial cells (HCECs) between the central and peripheral areas and between
      younger and older donors. METHODS: Human corneas were obtained from the eye bank
      and separated into two groups: young (younger than 30 years) and old (older than
      50 years). Corneas were cut in quarters and a 2-mm scrape wound was created in
      the endothelium from the periphery to the center. Unwounded endothelium acted as
      a negative control. Corneal pieces were incubated for 24, 36, 48, 60, 72, 84, and
      96 hours in medium containing 8% fetal bovine serum (FBS) plus additional growth
      factors. Tissue was fixed, immunostained for minichromosome maintenance (MCM)-2,
      a marker of replication competence, and mounted in medium containing propidium
      iodide (PI) to visualize all nuclei. Fluorescence microscope images were used to
      count PI-stained and MCM2-positive HCECs in three 100-microm2 areas within the
      central and peripheral wound area. Results are expressed as mean number of
      cells/100 microm2. Senescent HCECs in ex vivo corneas were identified by staining
      for senescence-associated beta-galactosidase activity (SA-beta-Gal). Whole
      corneas were cut in quarters and incubated in staining solution containing SA
      beta-Gal at pH 6.0. The number of cells stained for SA-beta-Gal and the grade of
      SA-beta-Gal intensity in three 100-microm2 areas were averaged for the central
      and peripheral areas from each donor. For all studies, results were compared
      between central and peripheral cornea and between younger and older donors.
      RESULTS: In both age groups (n = 4/group), cells repopulated the wound area in a
      time-dependent manner. In corneas from older donors, significantly fewer HCECs
      migrated into the wound bed in the central cornea than in the periphery. At each
      time point, the density of cells in the central wound area was lower in corneas
      from older donors than from younger donors. In both age groups, the mean
      percentage of MCM2-positive cells increased with time until wound healing. In
      both age groups, more MCM2-positive cells were present in the wounded area of the
      peripheral than of the central cornea. At 36, 48, 60, and 72 hours after
      wounding, the percentage of MCM2-positive cells in the central or peripheral area
      of older corneas was significantly less than in the corresponding region in
      younger corneas. No MCM2-positive staining was observed in unwounded areas at any
      time point. HCECs in corneas from younger donors (n = 4) showed little to no SA
      beta-Gal activity in either the central or peripheral area. SA-beta-Gal activity
      was easily detectable in corneas from older donors (n = 4) and a significantly
      higher percentage of central HCECs showed strong SA-beta-Gal activity compared
      with HCECs in the periphery. CONCLUSIONS: In ex vivo corneas, HCECs from the
      peripheral area retain higher replication competence, regardless of donor age.
      HCECs in the central area of corneas from older donors retain replicative
      competence, but the relative percentage of cells that are competent to replicate
      is significantly lower than in the periphery or in the central area of corneas
      from younger donors. This reduction in replicative competence negatively
      correlates with the observed increase in the population of central HCECs
      exhibiting senescence-like characteristics.

PMID- 16565373
TI  - Distribution of CESP-1 protein in the corneal endothelium and other tissues.
AB  - PURPOSE: The gene expression profile of human corneal endothelium (CE) was
      established with the gene signature system. A novel gene, GS3582, was abundantly
      transcribed in the CE compared with other tissues according to a human gene
      expression database. This protein was designated corneal endothelium-specific
      protein (CESP)-1. The tissue distribution and subcellular localization of CESP-1
      was assessed in humans and mice, to investigate its physiological function.
      METHODS: Rabbit and mouse CESP-1 cDNAs were cloned, and a polyclonal anti-human
      CESP-1 antibody (Ab) and anti-mouse N- or C-terminal ovary-specific acidic
      protein (OSAP)-1 Ab were produced. CESP-1 expression was investigated in human
      and mouse corneas by Western blot and/or immunohistochemical analysis. The
      distribution of CESP-1 in human tissues was also examined by Western blot
      analysis. To identify the subcellular localization of CESP-1, cultured human CE
      was colabeled with anti-human CESP-1 Ab and anti-cytochrome c monoclonal Ab or
      anti-GRP78 monoclonal Ab for confocal microscopy. RESULTS: The rabbit and mouse
      CESP-1 cDNA sequences contained an open reading frame coding 242 and 283 amino
      acids, respectively. Mouse CESP-1 was entirely consistent with mouse OSAP.
      Western blot analysis showed that CESP-1 was expressed in the human corneal
      epithelium, CE, cultured CE, brain, testis, and ovary. Mouse CESP-1 was also
      expressed in mouse corneal epithelium and CE with anti-mouse C- but not N
      terminal OSAP Ab according to immunohistochemical analysis. Subcellular
      localization of CESP-1 to the mitochondria was demonstrated in cultured human CE.
      The N-terminal of CESP-1, possessing a mitochondrial targeting sequence, may be
      processed after the protein is imported into the mitochondria. CONCLUSIONS: CESP
      1 was distributed in the corneal epithelium, the CE and cultured human CE, as
      well as the brain, testis, and ovary. CESP-1 was localized in the mitochondria of
      cultured human CE. These findings may provide some clues about the physiological
      function of CESP-1.

PMID- 16565374
TI  - The topography of the central and peripheral cornea.
AB  - PURPOSE: To investigate the topography of the central and peripheral cornea in a
      group of young adult subjects with a range of normal refractive errors. METHODS:
      Corneal topography data were acquired for 100 young adult subjects by a method
      that allows central and peripheral maps to be combined to produce one large,
      extended corneal topography map. This computer-based method involves matching the
      common topographical features in the overlapping maps. Corneal height, axial
      radius of curvature, and axial power data were analyzed. The corneal height data
      were also fit with Zernike polynomials. RESULTS: Conic fitting to the corneal
      height data revealed the average apical radius (Ro) was 7.77 +/- 0.2-mm and
      asphericity (Q) was -0.19 +/- 0.1 for a 6-mm corneal diameter. The conic fit
      parameters were both found to change significantly for increasing corneal
      diameters. For a 10-mm corneal diameter, Ro was 7.72 +/- 0.2 mm and Q was -0.36
      +/- 0.1. A slight but significant meridional variation was found in Q, with the
      steepest principal corneal meridian found to flatten at a slightly greater rate
      than the flattest meridian. The RMS fit error for the conic section was found to
      increase markedly for larger corneal diameters. Higher-order polynomial fits were
      needed to fit the peripheral corneal data adequately. Analysis of the axial power
      data revealed highly significant changes occurring in the corneal best-fit
      spherocylinder with increasing distance from the corneal center. The peripheral
      cornea was found to become significantly flatter and to decrease slightly in its
      toricity. Individual subjects exhibited a range of different patterns of central
      and peripheral corneal topography. Several of the higher order corneal surface
      Zernike coefficients were found to change significantly with increasing corneal
      diameter. CONCLUSIONS: Highly significant changes occur in the shape of the
      cornea in the periphery. On average, the peripheral cornea becomes significantly
      flatter and slightly less astigmatic than the central cornea. A conic section is
      a poor estimator of the peripheral cornea.

PMID- 16565375
TI  - Chitosan nanoparticles as a potential drug delivery system for the ocular
      surface: toxicity, uptake mechanism and in vivo tolerance.
AB  - PURPOSE: To study the in vitro and in vivo interaction of chitosan nanoparticles
      (CSNPs), a new particulate drug carrier, with epithelial cells on the ocular
      surface. METHODS: CSNPs labeled with fluorescein isothiocyanate-bovine serum
      albumin were produced by ionotropic gelation. Human conjunctival epithelial cells
      (IOBA-NHC) were exposed for 15, 30, 60, and 120 minutes to three different CSNP
      concentrations. Immediately after treatment and after a 24-hour recovery period
      in culture medium, cell survival, and viability were measured. The association of
      CSNPs with IOBA-NHC cells was investigated by confocal microscopy. The influence
      of temperature and the effect of metabolic inhibition were studied by
      fluorometry. The in vivo uptake and acute tolerance of the ocular surface to
      CSNPs were evaluated in rabbits. RESULTS: Cell survival and viability of CSNP
      exposed cells were equivalent to that of the control. Uptake of CSNPs was
      continuous for the 2-hour duration of these experiments and was temperature
      dependent. Metabolic inhibition by sodium azide had no effect on CSNP uptake. The
      rabbit ocular surface showed no signs of inflammation or alteration after CSNP
      exposure compared with the control. Fluorescence microscopy of rabbit eyeball and
      lid sections confirmed in vivo uptake by conjunctival and corneal epithelia.
      CONCLUSIONS: CSNPs were internalized by IOBA-NHC cells by an active transport
      mechanism that did not compromise cell viability. Moreover, these nanoparticles
      were well tolerated by the ocular surface tissues. These facts add further
      support for the potential use of these colloidal systems to delivery drugs to the
      ocular surface.

PMID- 16565377
TI  - Processes involved in oculomotor adaptation to eccentric reading.
AB  - PURPOSE: Adaptation to eccentric viewing in subjects with a central scotoma
      remains poorly understood. The purpose of this study was to analyze the
      adaptation stages of oculomotor control to forced eccentric reading in normal
      subjects. METHODS: Three normal adults (25.7 +/- 3.8 years of age) were trained
      to read full-page texts using a restricted 10 degrees x 7 degrees viewing window
      stabilized at 15 degrees eccentricity (lower visual field). Gaze position was
      recorded throughout the training period (1 hour per day for approximately 6
      weeks). RESULTS: In the first sessions, eye movements appeared inappropriate for
      reading, mainly consisting of reflexive vertical (foveating) saccades. In early
      adaptation phases, both vertical saccade count and amplitude dramatically
      decreased. Horizontal saccade frequency increased in the first experimental
      sessions, then slowly decreased after 7 to 15 sessions. Amplitude of horizontal
      saccades increased with training. Gradually, accurate line jumps appeared, the
      proportion of progressive saccades increased, and the proportion of regressive
      saccades decreased. At the end of the learning process, eye movements mainly
      consisted of horizontal progressions, line jumps, and a few horizontal
      regressions. CONCLUSIONS: Two main adaptation phases were distinguished: a
      "faster" vertical process aimed at suppressing reflexive foveation and a "slower"
      restructuring of the horizontal eye movement pattern. The vertical phase
      consisted of a rapid reduction in the number of vertical saccades and a rapid but
      more progressive adjustment of remaining vertical saccades. The horizontal phase
      involved the amplitude adjustment of horizontal saccades (mainly progressions) to
      the text presented and the reduction of regressions required.

PMID- 16565376
TI  - Temporal dynamics of ocular position dependence of the initial human vestibulo
      ocular reflex.
AB  - PURPOSE: While an ideal vestibulo-ocular reflex (VOR) generates ocular rotations
      compensatory for head motion, during visually guided movements, Listing's Law
      (LL) constrains the eye to rotational axes lying in Listing's Plane (LP). The
      present study was conducted to explore the recent proposal that the VOR's
      rotational axis is not collinear with the head's, but rather follows a time
      dependent strategy intermediate between LL and an ideal VOR. METHODS: Binocular
      LPs were defined during visual fixation in eight normal humans. The VOR was
      evoked by a highly repeatable transient whole-body yaw rotation in darkness at a
      peak acceleration of 2800 deg/s2. Immediately before rotation, subjects regarded
      targets 15 or 500 cm distant located at eye level, 20 degrees up, or 20 degrees
      down. Eye and head responses were compared with LL predictions in the position
      and velocity domains. RESULTS: LP orientation varied both among subjects and
      between individual subject's eyes, and rotated temporally with convergence by 5
      +/- 5 degrees (+/-SEM). In the position domain, the eye compensated for head
      displacement even when the head rotated out of LP. Even within the first 20 ms
      from onset of head rotation, the ocular velocity axis tilted relative to the head
      axis by 30% +/- 8% of vertical gaze position. Saccades increased this tilt.
      Regardless of vertical gaze position, the ocular rotation axis tilted backward 4
      degrees farther in abduction than in adduction. There was also a binocular
      vertical eye velocity transient and lateral tilt of the ocular axis. CONCLUSIONS:
      These disconjugate, short-latency axis perturbations appear intrinsic to the VOR
      and may have neural or mechanical origins.

PMID- 16565378
TI  - TNF-alpha-induced optic nerve degeneration and nuclear factor-kappaB p65.
AB  - PURPOSE: To characterize a model of optic nerve axonal degeneration induced by
      tumor necrosis factor (TNF)-alpha and to determine the role of nuclear factor
      (NF)-kappaB p65 in axonal degeneration. METHODS: Groups of rats were euthanatized
      at 1 day, 1 or 2 weeks, or 1 or 2 months after intravitreal injection of TNF
      alpha. Morphometric analyses of neurofilament- or Thy-1-positive cells, retinal
      ganglion cells (flat preparations stained with cresyl violet or retrograde
      labeling with a neurotracer), the number of axons, immunostaining for myelin
      basic protein, and TUNEL assays were performed. Levels of NF-kappaB p65 protein
      in retina and optic nerve were determined by Western blot analysis and
      immunohistochemistry. The effects of antisense oligodeoxynucleotide (AS ODN)
      against NF-kappaB p65 and helenalin, an inhibitor of NF-kappaB p65 activation, on
      TNF-alpha-induced optic nerve degeneration were determined by counting the number
      of axons. RESULTS: Intravitreal injections of TNF-alpha induced obvious axonal
      loss and extensive degeneration of the axons from 2 weeks to 2 months after
      injection, whereas significant retinal ganglion cell loss was noted only at 2
      months after injection. NF-kappaB p65 was increased in the optic nerve but not in
      the retina and was found to colocalize with ED-1 and Iba1, markers of microglia.
      Inhibition of NF-kappaB p65 with AS ODN or helenalin significantly ameliorated
      the effects of TNF-alpha-mediated axonal loss. CONCLUSIONS: TNF-alpha causes
      axonal degeneration with probable delayed loss of retinal ganglion cell bodies.
      NF-kappaB p65 may play a pivotal role in axonal degeneration, with the possible
      involvement of microglial cells.

PMID- 16565380
TI  - Saccade adaptation in Williams-Beuren Syndrome.
AB  - PURPOSE: To investigate the capacity for rapid saccade adaptation in Williams
      Beuren Syndrome (WBS), a genetic neurodevelopmental disorder, in which it has
      been observed that saccadic accuracy is severely reduced. METHODS: Saccade
      amplitude modification was elicited by backward steps (30% of target
      eccentricity) during the primary saccade in a classic saccade-adaptation
      paradigm. RESULTS: Patients with WBS showed a significant decrease in saccade
      amplitude. Furthermore, we observed that higher saccade accuracy before
      adaptation was related to more adaptation. CONCLUSIONS: The increased variability
      in motor performance does not abolish the ability for saccadic adaptation in
      subjects with WBS. Our results are congruent with the notion that part of the
      behavioral deficits observed in WBS may have a cerebellar origin.

PMID- 16565379
TI  - Correlation of the multifocal visual evoked potential and standard automated
      perimetry in compressive optic neuropathies.
AB  - PURPOSE: To evaluate the relationship between abnormalities detected by the
      multifocal visual-evoked potential (mfVEP) compared with those detected by static
      achromatic automated perimetry in patients with compressive optic neuropathy.
      METHODS: Fifteen patients of mean age 50.8 years, with known compressive optic
      neuropathy from chiasmal lesions, underwent monocular mfVEP and 24-2 SITA
      standard Humphrey visual field (HVF; Carl Zeiss Meditec, Dublin CA) testing in
      each eye. Visual field spatial agreement and extent of involvement were analyzed
      by assigning a severity score to each quadrant, based on pattern deviation and
      amplitude deviation probability plots. RESULTS: HVF mean deviation (MD) was -6.54
      +/- 7.43 dB (mean), and the mfVEP mean AccuMap Severity Index (ASI; ObjectiVision
      Pty. Ltd., Sydney, Australia) score was 81 +/- 74. MD and ASI correlated
      significantly (r = -0.55, P = 0.024). Although both mfVEP and HVF reported
      approximately the same proportion of visual fields as abnormal (70%, 21/30, and
      87%, 26/30, respectively), 19% (5/26) with abnormal HVF were labeled normal or
      borderline by mfVEP. The agreement for field quadrants between instruments was
      69% (kappa = 0.33). mfVEP severity scores for quadrants and hemifields were
      higher than scores for HVF in the same eyes. The superotemporal quadrant showed
      the strongest correlation between techniques (r = 0.73, P = 0.002). CONCLUSIONS:
      In the first study to compare mfVEP to HVF in patients with compressive optic
      neuropathy, there was good qualitative and quantitative agreement between tests,
      though findings were in only modest agreement in some areas. The injury caused by
      compressive optic neuropathy may be usefully identified by mfVEP. Improved
      methods of analysis may increase the diagnostic utility of the method.

PMID- 16565381
TI  - IL-1 and TNF induction of matrix metalloproteinase-3 by c-Jun N-terminal kinase
      in trabecular meshwork.
AB  - PURPOSE: The cytokines TNF and IL-1 mediate the MMP-3 increase that occurs in
      response to trabecular meshwork (TM) treatment by laser trabeculoplasty. This MMP
      3 increase appears to play a key role in the efficacy of this treatment for open
      angle glaucoma. Protein kinase Cmu and the Erk mitogen-activated protein (MAP)
      kinases are essential signaling components in transducing MMP-3 increases
      produced by treatment of TM cells with these cytokines. Here, the involvement of
      the JNK-MAP kinase pathway in this process was evaluated. METHODS: Porcine TM
      cells were treated with TNFalpha, IL-1alpha, or IL-1beta. Changes in MMP-3 and
      MMP-9 protein levels in the media were then determined by Western immunoblot. The
      effect of JNK inhibitor 2 was evaluated. Changes in the level of phosphorylation
      of JNK, c-Jun, ATF-2, MKK4, and MKK7 were also determined at various times after
      TNFalpha or IL-1alpha treatment. A 2.3-kb MMP-3 promoter fragment was cloned into
      a secreted alkaline phosphatase reporter vector. This reporter construct was
      cotransfected into TM cells with a mammalian expression vector containing a
      dominant-negative mutant of JNK. The involvement of JNK activity in the TNFalpha
      and IL-1alpha induction of MMP-3 expression was then evaluated. RESULTS:
      TNFalpha, IL-1alpha, and IL-1beta increase media MMP-3 and MMP-9 protein levels,
      and JNK inhibitor 2 blocks these increases. JNK1/2, MKK4, c-Jun, and ATF-2
      phosphorylation levels increase in response to TNFalpha and IL-1alpha treatment.
      JNK inhibitor 2 pretreatment blocks these c-Jun and ATF-2 phosphorylation
      increases. Dominant-negative JNK dramatically reduces the MMP-3 promoter-driven
      reporter activity induced by these cytokines. CONCLUSIONS: JNK activity is
      necessary for the induction of MMP-3 and MMP-9 by TNFalpha, IL-1alpha, or IL
      1beta in TM cells. Phosphorylation of components of the JNK signaling pathway and
      of the transcription factors c-Jun and ATF-2 support a role for this pathway in
      the induction of MMP-3 and MMP-9 in the TM in response to these cytokines. Thus,
      at least three separate signal transduction pathways are necessary in this
      signaling event in TM cells.

PMID- 16565382
TI  - Retinal ganglion cell axotomy induces an increase in intracellular superoxide
      anion.
AB  - PURPOSE: Retinal ganglion cells (RGCs) undergo apoptosis after axonal injury. The
      time course of cell death is variable and depends in part on the degree of injury
      sustained. Decreasing reactive oxygen species (ROS) levels or shifting the redox
      state to reduction promotes the survival of RGCs in tissue culture after axotomy.
      It was hypothesized that a specific ROS, superoxide anion, acts as an
      intracellular signaling molecule for RGC death after axotomy. METHODS:
      Intracellular superoxide levels were measured after dissociation in retrograde
      labeled rat RGCs with use of the superoxide-sensitive fluorophores hydroethidium
      and MitoSOX Red. Having found a significant increase, the effect of axotomy was
      determined on superoxide levels independent of dissociation with an optic nerve
      crush model. RESULTS: Optic nerve crush caused RGCs to undergo a superoxide
      burst. The burst was asynchronous and was manifested in only a fraction of cells
      at any given time. Neurotrophin deprivation was not responsible for the
      superoxide burst because it was not prevented by incubation with the neurotrophic
      factors brain-derived neurotrophic factor, ciliary neurotrophic factor,
      forskolin, or insulin. Several inhibitors of intracellular superoxide generation
      were studied, but only antimycin A, which inhibits complex III of the
      mitochondrial electron transport chain, blocked the increase in superoxide.
      CONCLUSIONS: These findings suggest that superoxide generated in the
      mitochondrial electron transport chain could be a parallel system to neurotrophic
      deprivation for signaling cell death after axonal injury.

PMID- 16565383
TI  - Of mice and men: tyrosinase modification of congenital glaucoma in mice but not
      in humans.
AB  - PURPOSE: Primary congenital glaucoma (PCG) is an autosomal recessive ocular trait
      caused by mutations in the gene for cytochrome P4501B1 (CYP1B1). Although PCG is
      often considered to be fully penetrant, the disease shows 50% penetrance in some
      Saudi Arabian families. The familial segregation of the nonpenetrance suggests a
      genetic modifier. Recently, tyrosinase (Tyr) deficiency was found to worsen the
      drainage structure/ocular dysgenesis phenotype of Cyp1b1-/- mice, suggesting that
      Tyr is a modifier of the phenotype. In the current study, tyrosinase (TYR) was
      investigated in human PCG. METHODS: A genome-wide screen, a single nucleotide
      polymorphism (SNP) analysis in the TYR chromosomal region 11q13-q21, and
      sequencing of the TYR gene was performed with individuals from Saudi Arabian
      families with multiple, clinically confirmed, molecularly proven, nonpenetrant
      members. RESULTS: The study outcome did not support TYR as a modifier of the PCG
      phenotype in this population. The sequencing data showed no TYR mutations in the
      nonpenetrant family members and no difference in polymorphism frequencies between
      nonpenetrant or fully penetrant families. CONCLUSIONS: TYR is not a modifier of
      the CYP1B1-associated PCG phenotype in the Saudi Arabian population.

PMID- 16565384
TI  - Detection of differentially expressed glycogenes in trabecular meshwork of eyes
      with primary open-angle glaucoma.
AB  - PURPOSE: To identify differentially expressed glycogenes in trabecular meshwork
      (TM) of eyes with primary open-angle glaucoma (POAG). METHODS: Total RNA was
      isolated from TM of cadaveric eyes derived from donors with diagnosed glaucomas
      of different etiologies and from normal control subjects. RNA was amplified and
      hybridized to the GLYCOv2 oligonucleotide microarray that contains probes for
      carbohydrate-binding proteins, glycosyltransferases, and other genes involved in
      the regulation of glycosylation. Statistical analysis was used to identify
      differentially expressed genes between normal and POAG samples. RESULTS: This
      study revealed that POAG TM and normal TM have distinct gene expression profiles.
      Of the 2001 genes on the array, 19 genes showed differential expression of
      greater than 1.4-fold in POAG. Mimecan and activinA, which have been shown to be
      upregulated in models of glaucoma, were both found to be elevated in POAG TM.
      Many genes were identified for the first time to be differentially regulated in
      POAG. Among the upregulated genes were: (1) cell adhesion molecules including
      platelet endothelial cell adhesion molecule-1 and P-selectin, both of which are
      targets of NFkappaB, which has been shown to be activated in glaucomatous TM; (2)
      lumican, a core protein of keratan sulfate proteoglycans; and (3) the receptor
      for IL6, a cytokine that has been shown to be upregulated in TM in response to
      elevated intraocular pressure. Among the downregulated genes were chondroitin-4-O
      sulfotransferase involved in the synthesis of chondroitin sulfate chains and the
      receptor for PDGFbeta, a growth factor that has been shown to stimulate both TM
      cell proliferation and phagocytic activity. Results for several genes were
      confirmed by RTq-PCR. CONCLUSIONS: Microarray technology was used to show, for
      the first time, that POAG TM has a distinct glycogene expression profile.
      Differentially expressed glycogenes identified in this study have not been
      previously investigated for their role in the pathogenesis of POAG and thus are
      novel factors for further study of the mechanism of the disease and for their
      possible use as diagnostic markers.

PMID- 16565385
TI  - p38 inhibitors prevent TGF-beta-induced myofibroblast transdifferentiation in
      human tenon fibroblasts.
AB  - PURPOSE: The role of mitogen-activated protein kinase (MAPK) pathways in TGF-beta
      induced myofibroblast transdifferentiation of human tenon fibroblasts (HTFs) was
      investigated to identify potential pharmacologic targets for the inhibition of
      scarring after glaucoma surgery. METHODS: TGF-beta-dependent activation of Smad2,
      p38, and Erk-1/2 was examined by Western blot analysis. TGF-beta-induced mRNA
      expression of collagen Ialpha1, fibronectin, and the myofibroblast
      transdifferentiation marker alpha smooth muscle actin (alpha-SMA) was analyzed by
      real-time RT-PCR. alpha-SMA protein expression and subcellular distribution were
      determined by Western blot analysis and immunofluorescence cytochemistry.
      Fibroblast contractility was assessed in three-dimensional collagen gel
      contraction assays, stress fiber assembly with rhodamine-phalloidin stains, and
      confocal microscopy. Cell proliferation was measured with an MTT assay. Specific
      pharmacologic kinase inhibitors were used to characterize the involvement of MAPK
      dependent pathways. RESULTS: TGF-beta stimulation of HTF induced a rapid and
      transient activation of Smad2 and Erk, whereas p38 activation was biphasic and
      sustained. After 24 hours of TGF-beta stimulation, increased levels of collagen
      Ialpha1, fibronectin, and alpha-SMA transcripts were detected. After 3 days of
      stimulation, HTF displayed increased alpha-SMA protein levels, enhanced
      contractility, and assembly of actin stress fibers. TGF-beta also induced HTF
      proliferation. Specific p38 inhibitors prevented all these aspects of TGF-beta
      induced myofibroblastic transdifferentiation. CONCLUSIONS: Pharmacologic
      inhibition of p38 abrogates TGF-beta-induced myofibroblast transdifferentiation,
      reduces extracellular matrix protein expression and HTF proliferation, and may
      therefore serve to inhibit scarring after glaucoma surgery.

PMID- 16565386
TI  - HTLV-1 infection of human retinal pigment epithelial cells and inhibition of
      viral infection by an antibody to ICAM-1.
AB  - PURPOSE: To examine whether human T-cell leukemia virus type 1 (HTLV-1) could
      infect a human retinal pigment epithelial (RPE) cell line, ARPE-19, in vitro and
      to investigate its regulation. METHODS: A coculture system with ARPE-19 and
      irradiated cells of an HTLV-1-producing T-cell line, MT2 was used to determine
      the permissivity of RPE to HTLV-1 infection in vitro. The susceptibility to HTLV
      1 was assessed by detection of viral DNA using the polymerase chain reaction
      (PCR), viral mRNA transcripts with reverse transcription PCR (RT-PCR) and viral
      antigen by immunofluorescence staining. An HTLV-1 Tax-activated HTLV-LTR
      luciferase reporter assay was developed to measure viral infection
      quantitatively. The ICAM-1 expression on cocultured ARPE-19 cells was detected by
      flow cytometry and an ICAM-1-neutralizing antibody was used to test ICAM-1's role
      in the HTLV-1 infection of ARPE-19 cells. The regulation of HTLV-1 infection was
      investigated by culturing ARPE-19 cells with proinflammatory cytokines. RESULTS:
      HTLV-1 infected ARPE-19 cells in vitro. The infection correlated with elevated
      expression of intercellular adhesion molecule (ICAM)-1 on the surface of ARPE-19
      cells. ICAM-1-neutralizing antibody dramatically inhibited viral infection.
      Furthermore, proinflammatory cytokines dramatically suppressed HTLV-1 viral
      infection. CONCLUSIONS: The tropism of HTLV-1 to retinal pigment epithelium could
      provide an explanation for the pathogenesis of HTLV-1-related ophthalmic
      diseases. A better understanding of specific roles of proinflammatory cytokines
      in the development of ophthalmic diseases may be beneficial for treatment.

PMID- 16565387
TI  - Methotrexate reduces the complications of endophthalmitis resulting from
      intravitreal injection compared with dexamethasone in a rabbit model.
AB  - PURPOSE: The incidence of infectious endophthalmitis associated with intravitreal
      injection (IVI) of steroid has been reported to be as high as 0.87%. This study
      was designed to investigate whether the antimicrobial activity of intravitreal
      methotrexate (MTX) alters the incidence or course of bacterial endophthalmitis
      associated with IVI in a rabbit model. METHODS: A rabbit model of endophthalmitis
      induced by Staphylococcus epidermidis (S) was established. Six groups of rabbits
      had IVI of sterile balanced salt solution (BSS), MTX (400 microg), dexamethasone
      (Dex, 200 microg), S, S and MTX (S-MTX), or S and dexamethasone (S-Dex). On days
      0, 1, 3, 6, 10, and 14, total intraocular inflammation was measured in each
      animal. Vitritis was graded by the degree of vitreal haze. An intravitreal tap
      was performed on two animals from groups S, S-Dex, and S-MTX. A histopathologic
      study was performed on day 14. RESULTS: No endophthalmitis was observed in the
      control groups BSS, MTX, and Dex. Group S-Dex had the highest and group S-MTX had
      the least total ocular inflammation and vitritis scores from days 3 to 14. The
      difference in total inflammation and vitritis among groups S, S-Dex, and S-MTX is
      significant (P = 0.046 and P = 0.001, respectively). Live bacteria were isolated
      only from groups S and S-Dex. Pathology revealed severe ocular destruction in
      groups S and S-Dex and intact structures in group S-MTX. CONCLUSIONS: MTX appears
      to reduce the risk of development of bacterial endophthalmitis and ocular
      destruction associated with IVI compared with Dex. IVI of MTX may be a safer
      alternative than steroid injection in treating noninfectious uveitis.

PMID- 16565388
TI  - Immunogenicity and antigenicity of allogeneic amniotic epithelial transplants
      grafted to the cornea, conjunctiva, and anterior chamber.
AB  - PURPOSE: To determine the immunogenic characterization of amniotic epithelium
      (AE), by examining the fate of allogeneic AE grafts heterotopically transplanted
      in the eye. METHODS: Intact AE from enhanced green fluorescence protein (EGFP)
      transgenic mice (C57BL/6 background) and wild-type C57BL/6 mice were transplanted
      onto cornea or conjunctiva, or inserted into the anterior chamber (AC) of normal
      BALB/c mice, C57BL/6 mice, or BALB/c mice presensitized to donor antigens. For
      repeated AE transplantation experiments, AE was grafted in the other eye 7 days
      after the first grafting. Graft fate was assessed clinically and histologically
      at selected intervals after grafting. Infiltrating inflammatory cells were
      examined immunohistochemically. Sensitization to alloantigens by AE was assessed
      by the delayed hypersensitivity (DH) response. RESULTS: In normal recipients,
      GFP+ cells were absent in EGFP donor-derived AE grafts by day 21 on cornea and by
      day 7 on conjunctiva. AE grafts implanted in the AC survived for >8 weeks. In
      presensitized recipients and recipients that underwent repeated AE implantation,
      graft survival was markedly shorter than in normal recipients. DH was induced at
      2 weeks, but failed to be induced at 4 weeks after grafting on cornea or at 8
      weeks after grafting on conjunctiva and in the AC of normal recipients.
      CONCLUSIONS: Fresh allogeneic AE expressed immunogenicity when placed on the
      ocular surface, although no memory of allospecific DH was acquired. Allogeneic AE
      is clearly vulnerable to immune rejection in specifically sensitized recipients.

PMID- 16565389
TI  - CD8+ T regulatory cells use a novel genetic program that includes CD103 to
      suppress Th1 immunity in eye-derived tolerance.
AB  - PURPOSE: The peripheral tolerance that arises after injection of antigen into the
      anterior chamber (anterior chamber-associated immune deviation; ACAID) is
      associated in part with CD8+ T cells that suppress the expression of Th1 and Th2
      immunity. The purpose of these studies was to determine the genes and molecules
      that are critical for CD8+ T regulatory cell (T reg) functions in ACAID. METHODS:
      Ovalbumin (OVA)-specific CD8+ T cells from T-cell receptor (TCR) transgenic OT-1
      mice acquire efferent regulatory properties similar to in vivo-generated CD8+ T
      regs after stimulation with OVA-pulsed TGF-beta2-treated APCs. Changes in the
      genetic program associated with acquisition of efferent regulatory function in OT
      1 CD8+ T cells in vitro were determined by DNA microarray analyses and confirmed
      by RT-PCR analyses and biological assays. RESULTS: T regulatory OT-1 T cells
      acquired a novel transcriptional pattern indicative of their function. Genes for
      molecules associated with TGF-beta function, resistance to TCR-triggered
      apoptosis, and localization of cells to antigen deposition in peripheral tissues
      were upregulated, and genes related to cytolytic function were downregulated.
      Further study showed that CD103, a cell-adhesion molecule that binds E-cadherin,
      was highly upregulated in in vivo-generated ACAID T regs and was necessary for
      their suppression of T-cell activation in vitro. CONCLUSIONS: OT-1 CD8 T cells
      modulated in vitro by exposure to antigen-pulsed, TGF-beta2-treated APCs
      expressed genes related to immune suppression. Thus, the necessity for CD103
      emerges in the efferent CD8+ T-cell regulatory mechanisms in eye-derived
      tolerance.

PMID- 16565390
TI  - Blockade of the interaction of leukotriene b4 with its receptor prevents
      development of autoimmune uveitis.
AB  - PURPOSE: To investigate the role of leukotriene B4 (LTB4) and its receptor BLT1
      in the pathogenesis of mouse uveitis. METHODS: Experimental autoimmune uveitis
      (EAU) was induced in B10RIII mice by immunization of interphotoreceptor retinoid
      binding protein (IRBP; peptide sequence 161-180) or in C57BL/6 (B6) mice by
      transfer of activated T cells specific for IRBP1-20. The animals were then
      treated with and without the BLT1 receptor antagonist, CP105696, at the disease
      onset after immunization or at day 0 or day 6 after T-cell transfer. EAU was also
      induced in wild-type B6 (WT) and BLT1-deficient (BLT1-/-) mice by reciprocal
      transfer of the T cells from B6 to BLT1-deficient mice and vise versa. Clinical
      signs of inflammation and ocular histology were compared. The chemotactic
      activity of LTB4 on naive and IRBP-specific autoreactive T cells as well as
      effector leukocytes was examined. RESULTS: The treatment of CP105696, greatly
      reduced the intensity of ongoing disease. IRBP1-20-specific T cells derived from
      wild-type B6 mice induced only mild uveitis in syngeneic BLT1-deficient mice and
      that IRBP1-20-specific T cells derived from BLT1-/- mice induced milder disease
      in wild-type B6 mice than those derived from wild-type B6 mice, suggesting that
      expression of the LTB4 receptor on both activated autoreactive T cells and
      effector leukocytes was necessary for ocular inflammation to occur. Consistent
      with these data, transfer of autoreactive T cells from B6 mice to 5-lipoxygenase
      deficient (5-LO-/-) mice, which have a functional defect in LTB4 expression, also
      failed to induce uveitis in the recipient mice. CONCLUSIONS: The results
      demonstrate a critical role for LTB4 in ocular inflammation and in the
      development and progression of EAU and suggest a new potential target for
      therapeutic intervention in this disease.

PMID- 16565391
TI  - Circulating anti-galectin-1 antibodies are associated with the severity of ocular
      disease in autoimmune and infectious uveitis.
AB  - PURPOSE: Galectin (Gal)-1, an endogenous lectin found at sites of immune
      privilege, plays a critical role in the regulation of the immune response.
      Therapeutic administration of Gal-1 or its genetic delivery suppresses chronic
      inflammation in experimental models of autoimmunity. The purpose of this work was
      to investigate the occurrence of circulating anti-Gal-1 antibodies in patients
      with autoimmune and infectious uveitis as potential determinant factors of
      disease progression. METHODS: IgG, IgE, and IgA anti-Gal-1 antibodies were
      assessed by ELISA and Western blot in sera from patients with autoimmune (n = 47)
      and infectious (n = 15) uveitis compared with healthy control subjects (n = 30).
      The frequency of anti-Gal-1 antibodies was examined in patients experiencing poor
      clinical outcome (n = 21) or good evolution (n = 9). Anti-Gal-1 antibodies were
      eluted by incubating patient sera with nitrocellulose filters adsorbed with rGal
      1. The ability of these antibodies to recognize retinal tissue was assessed by
      ELISA, Western blot, and immunohistochemistry. RESULTS: IgE, IgG, and IgA anti
      Gal-1 antibodies were increased in sera from patients with autoimmune uveitis (P
      < 0.001 vs. controls) and toxoplasmic retinochoroiditis (P < 0.001). The level of
      anti-Gal-1 IgE and IgG antibodies was associated with progressive disease and
      poor outcome in autoimmune and infectious uveitis. Furthermore, these antibodies
      strongly immunoreacted with retinal lysates and recognized retinal structures
      mainly photoreceptors in retinal sections. CONCLUSIONS: Anti-retinal Gal-1
      antibodies are present in sera from patients with uveitis and can be associated
      with the progression of ocular disease, suggesting their potential use in follow
      up observations of these patients.

PMID- 16565392
TI  - Cytokine profile in aqueous humor and sera of patients with infectious or
      noninfectious uveitis.
AB  - PURPOSE: To determine the cytokine expression profile at the protein level in
      aqueous humor (AqH) and sera of patients with uveitis. METHODS: Patients with
      various clinical entities of strictly diagnosed infectious or noninfectious
      uveitis were tested. AqH and sera were collected from patients with uveitis. AqH
      was also collected during surgery from patients with cataract, as control
      specimens. Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and
      interleukin (IL)-2, -4, -5, and -10 were measured from nondiluted samples
      simultaneously, with microparticle-based flow cytometric analysis. RESULTS: In
      AqH IFN-gamma was the most abundant cytokine in both infectious (mean, 3240.5
      pg/mL) and noninfectious (mean, 115.6 pg/mL) uveitis, and IL-10 was the second
      (mean, 402.1 pg/mL, infectious uveitis; 7.5 pg/mL, noninfectious uveitis). The
      expression level of other cytokines in AqH was generally higher in infectious
      uveitis than in noninfectious uveitis, but the levels were lower than that of IL
      10. There was no remarkable difference, however, in the cytokine expression
      pattern in AqH of the different clinical entities of uveitis. Sera from patients
      with noninfectious uveitis contained IFN-gamma (mean, 45.0 pg/mL), but the other
      serum cytokines in both types of uveitis were low or under the detectable level.
      CONCLUSIONS: IFN-gamma is the most abundant cytokine in infectious and
      noninfectious uveitis, with a remarkable difference between the two groups. The
      data suggest that cytokines in AqH of infectious uveitis are locally produced,
      whereas in noninfectious uveitis, IFN-gamma is produced both in the eye and the
      peripheral blood.

PMID- 16565394
TI  - Oxygen distribution in the rabbit eye and oxygen consumption by the lens.
AB  - PURPOSE: Excessive exposure to oxygen has been proposed to be a risk factor for
      nuclear cataracts. For a better understanding of the metabolism of oxygen in the
      eye, oxygen distribution was mapped in the intraocular fluids, and the rate of
      oxygen consumption by the lens in rabbits breathing different levels of oxygen
      was calculated. METHODS: Young albino rabbits were anesthetized, intubated, and
      exposed to normoxic, hypoxic, or hyperoxic conditions. The hemoglobin saturation
      of the blood was monitored with a pulse oximeter, and arterial oxygen levels were
      measured with a blood gas analyzer. A fiberoptic optical oxygen sensor (optode)
      was used to determine oxygen levels in different regions of the eye. Oxygen flux
      across the posterior of the lens was calculated from the measured oxygen
      gradients in the vitreous chamber. RESULTS: Oxygen levels in the ocular fluids
      changed markedly when rabbits breathed air made hypoxic or hyperoxic. Oxygen
      levels were highest near the retinal vasculature, the iris vasculature, and the
      inner surface of the central cornea. Compared with nearby regions, oxygen levels
      were decreased in the aqueous humor closest to the pars plicata of the ciliary
      body and near the anterior chamber angle. Oxygen levels were generally lower
      closer to the lens. From the oxygen gradients in the vitreous body, oxygen
      consumption by the posterior half of the lens was calculated to be 0.2 to 0.4
      microL/h under normoxic conditions. Oxygen consumption by the posterior of the
      lens increased in proportion to the amount of oxygen supplied. CONCLUSIONS:
      Intraocular oxygen is mostly derived from the retinal and iris vasculature and by
      diffusion across the cornea. Freshly secreted aqueous humor and the aqueous humor
      in the anterior chamber angle are relatively depleted of oxygen. The marked
      increase in oxygen consumption that occurs when the lens is exposed to increased
      oxygen is likely to result in the production of higher levels of reactive oxygen
      species and may provide a link between elevated oxygen levels and the risk of
      nuclear cataracts.

PMID- 16565393
TI  - The C terminus of lens aquaporin 0 interacts with the cytoskeletal proteins
      filensin and CP49.
AB  - PURPOSE: Aquaporin 0 (AQP0), the most abundant membrane protein in the lens, is a
      water-permeable channel, has a role in fiber cell adhesion, and is essential for
      fiber cell structure and organization. The purpose of this study was to identify
      proteins that interact with the C terminus of AQP0, by using a proteomics
      approach, and thus further elucidate the role of AQP0 in the human lens. METHODS:
      AQP0 C-terminal peptides and AQP0 antibody affinity chromatography were used for
      affinity purification of interacting human lens proteins. Purified proteins were
      digested with trypsin, analyzed by liquid chromatography (LC)-tandem mass
      spectrometry and identified after database searching and manual examination of
      the mass spectral data. Colocalization of AQP0 with filensin and CP49, two
      proteins identified after mass spectrometric analysis, were examined by
      immunoconfocal and immunoelectron microscopy of lens sections. RESULTS: The
      proteomics approach used to identify affinity-purified proteins revealed the lens
      specific intermediate filament proteins filensin and CP49. With immunoconfocal
      microscopy, regions of colocalization of AQP0 with filensin and CP49 at the fiber
      cell plasma membrane in the lens cortex were defined. Immunoelectron microscopy
      confirmed that filensin and AQP0 were present in the same membrane compartments.
      CONCLUSIONS: These studies suggest a novel interaction between an aquaporin water
      channel and intermediate filaments, an interaction through which AQP0 may
      maintain lens fiber cell shape and organization.

PMID- 16565395
TI  - Regulation of subfoveal choroidal blood flow in age-related macular degeneration.
AB  - PURPOSE: To assess the capability of the subfoveal choroidal circulation to
      regulate its blood flow in response to an acute increase in ocular perfusion
      pressure in the eyes of healthy elderly persons or of subjects with neovascular
      age-related macular degeneration (AMD). METHODS: Changes of subfoveal choroidal
      blood velocity (ChBVel), volume (ChBVol), and flow (ChBF) induced by isometric
      exercise were determined using laser Doppler flowmetry (LDF) in 19 young healthy
      volunteers (group 1), 24 elderly healthy volunteers with mild macular pigment
      distribution changes (group 2), and 23 subjects with subfoveal classic
      neovascularization caused by AMD (group 3). RESULTS: Isometric exercise induced
      significant increases in mean ocular perfusion pressure (PPm) of 19.5% +/- 4.9%,
      20.2% +/- 3.8%, and 23.2% +/- 4.2%, for groups 1, 2, and 3, respectively (mean +/
      95% confidence interval). In groups 1 and 2, the increase in PPm did not induce
      significant changes in the mean values of the different LDF parameters. In group
      3, however, ChBF increased significantly by 12.4% +/- 5.0%. No significant
      correlations were found between age and the changes of each of the LDF parameters
      and of PPm at the end of squatting for the young and elderly healthy groups.
      CONCLUSIONS: In response to an acute, moderate increase in PPm induced by
      isometric exercise, subfoveal choroidal blood flow behaves similarly in young and
      elderly healthy persons and is not significantly different from its value at
      rest. In contrast, in patients with neovascular AMD, this flow increases,
      indicating altered regulation in response to the increase in PPm.

PMID- 16565396
TI  - Experimental retinal ablation using a fourth-harmonic 266 nm laser coupled with
      an optical fiber probe.
AB  - PURPOSE: To explore the ablation potential of 266 nm laser pulses, with an intact
      porcine retina preparation. METHODS: Segments of porcine eyes were used in an in
      vitro preparation in which localized areas of intact retina and choroid could be
      exposed to 266 nm laser irradiation. The segments of ocular tissue were bathed in
      fluid, to mimic the intraocular environment. Contact between the probe and the
      retinal surface was established before the first laser pulse. Single or multiple
      pulses (5-7 ns duration) at fluence levels of 0.4 to 1.2 J/cm2 were delivered via
      a tapered fiber optic probe with a tip size of approximately 110 microm. The
      retinal tissue was then fixed and sectioned for histologic examination. The
      ablation depth and extent of damage were measured and related to fluence level
      and the number of pulses applied. RESULTS: Ablation of the inner retina was
      achieved by single pulses at fluence levels of 0.6 J/cm2 and higher. The depth of
      retinal ablation was highly dependent on fluence for lesions generated with a
      single pulse but less so for multiple pulses (3-10), particularly at lower
      fluence levels. Higher numbers of pulses (50-100) did not increase ablation depth
      in a predictable manner. CONCLUSIONS: Pulsed laser (266 nm) irradiation at low
      pulse counts and high fluence levels is a possible alternative for localized
      retinal ablation with minimal collateral damage in a fluid environment.

PMID- 16565397
TI  - Role of mitochondrial superoxide dismutase in the development of diabetic
      retinopathy.
AB  - PURPOSE: Apoptosis of retinal capillary cells is an early event in the
      pathogenesis of retinopathy in diabetes, and oxidative stress has been linked to
      accelerated apoptosis of retinal capillary cells. Mitochondria are the major
      endogenous source of superoxide, and superoxide is considered to be a causal link
      between elevated glucose and the major biochemical pathways postulated to be
      involved in the development of vascular complications in diabetes. The purpose of
      the present study is to determine the role of mitochondrial superoxide dismutase
      (MnSOD) in the development of diabetic retinopathy. METHODS: The effect of
      overexpression of MnSOD on glucose-induced endothelial cell oxidative stress,
      nitrosative stress, and apoptosis was determined by using bovine retinal
      endothelial cells. Furthermore, the effect of diabetes in rats (11 months'
      duration) on the activity and the mRNA expression of retinal MnSOD were also
      determined. RESULTS: MnSOD activity in the nontransfected control retinal
      endothelial cells was 20% compared with the total SOD activity and was increased
      to 60% in the MnSOD-transfected cells. MnSOD overexpression prevented a glucose
      induced increase in oxidative stress (8-hydroxy guanosine levels), nitrosative
      stress (nitrotyrosine formation), and apoptosis of retinal endothelial cells.
      MnSOD enzyme activity and its mRNA were decreased significantly in the retina
      obtained from the diabetic rats, and these abnormalities were prevented by long
      term lipoic acid therapy. CONCLUSIONS: The results of this study suggest a
      protective role for MnSOD in retinal capillary cell death and, ultimately, in the
      pathogenesis of retinopathy in diabetes. Understanding the role of MnSOD to
      modify the course of retinopathy could elucidate important molecular targets for
      future pharmacological interventions.

PMID- 16565399
TI  - Intravitreal moxifloxacin: retinal safety study with electroretinography and
      histopathology in animal models.
AB  - PURPOSE: To determine whether moxifloxacin can be used safely as an intraocular
      antibiotic, retinal safety of intravitreal moxifloxacin was studied with
      electroretinography (ERG) and histopathology in animal models. METHODS:
      Moxifloxacin was injected into mouse eyes at intravitreal concentrations of 5 to
      500 microg/mL and into rabbit eyes at 150 microg/mL. As the control, the vehicle
      was injected into the fellow eyes of each animal. Four weeks after injection, ERG
      recordings were performed, and animal eyes were processed for histologic
      examination. RESULTS: ERG studies showed no significant difference between
      control and moxifloxacin-injected eyes at any dose in either the mouse or rabbit
      model. Histologic examination revealed no retinal abnormality in mice at 5 to 100
      microg/mL or in rabbits at 150 microg/mL intravitreal moxifloxacin. In mice at
      500 microg/mL, occasional focal retinal necroses were observed, suggesting
      isolated retinal toxicity at this concentration of moxifloxacin. CONCLUSIONS:
      Intravitreal moxifloxacin, up to 100 microg/mL in mice or 150 microg/mL in
      rabbits, caused no ERG or retinal histologic abnormality. These results indicate
      that moxifloxacin is a safe intravitreal antibiotic in mouse and rabbit animal
      models. If proven safe and efficacious by further study in humans, intravitreal
      injection of moxifloxacin could be considered as an alternative to currently used
      antibiotics in selected patients with resistance or allergy to the more
      traditional antibiotics.

PMID- 16565398
TI  - SB-267268, a nonpeptidic antagonist of alpha(v)beta3 and alpha(v)beta5 integrins,
      reduces angiogenesis and VEGF expression in a mouse model of retinopathy of
      prematurity.
AB  - PURPOSE: To determine whether SB-267268, a nonpeptidic antagonist of the
      alpha(v)beta3 and alpha(v)beta5 integrins, attenuates angiogenesis in a murine
      model of retinopathy of prematurity (ROP) and alters the expression of vascular
      endothelial growth factor (VEGF) and its second receptor (VEGF-R2). METHODS: In
      receptor binding, SB-267268 exhibited nanomolar potency for human, monkey, and
      murine alpha(v)beta3 and alpha(v)beta5. SB-267268 inhibited the attachment of
      alpha(v)beta3-transfected HEK293 cells to microtiter plate wells precoated with
      RGD-containing matrix proteins, and vitronectin-mediated human and rat aortic
      smooth-muscle-cell migration. At postnatal day (P)12, C57BL/6 mice were exposed
      to 80% oxygen for 7 days followed by 7 days in room air (angiogenic period).
      Between P12 and P17, ROP mice were administered sterile saline (vehicle
      intraperitoneal [i.p.]) or SB-267268 (60 mg/kg bi-daily, i.p.). Shams were
      exposed to room air from P0 and administered either vehicle or SB-267268 during
      P12 to 17. In at least 3 randomly chosen paraffin sections from each eye, the
      number of blood vessel profiles in the inner retina were counted. In situ
      hybridization for VEGF and VEGFR-2 was performed on at least 8 randomly chosen
      paraffin sections from each eye. RESULTS: SB-267268 reduced pathologic
      angiogenesis in ROP mice by approximately 50% and had no effect on developmental
      retinal angiogenesis in shams. Both VEGF and VEGFR-2 mRNA were upregulated in the
      inner retina of ROP mice and reduced with SB-267268. CONCLUSIONS: Nonpeptidic
      inhibition of alpha(v)beta3 and alpha(v)beta5 integrins is effective in ROP and
      may be a suitable anti-angiogenic therapy for other ischemic retinal pathologies.

PMID- 16565400
TI  - Early supernormal retinal oxygenation response in patients with diabetes.
AB  - PURPOSE: To determine whether the human retinal oxygenation response (deltaPO2)
      to a hyperoxic provocation is abnormal in patients with type I diabetes. METHODS:
      Magnetic resonance imaging (MRI) was used to measure deltaPO2 during 100% oxygen
      breathing in patients with type I diabetes who had either no clinically
      detectable retinopathy (n = 5) or mild to moderate background diabetic
      retinopathy (BDR; n = 5) and in age-matched healthy control subjects (n = 7).
      RESULTS: Both the patients with diabetes and the control subjects exhibited a
      significant (P < 0.05) increase in the preretinal vitreous signal intensity on
      changing from room air breathing to oxygen inhalation (i.e., 5 minutes). However,
      only diabetic patients demonstrated significant (P < 0.05) increases in deltaPO2
      between measurements made at 5 minutes of oxygen inhalation and measurements at
      longer durations of hyperoxia (15, 25, and 35 minutes). Furthermore, deltaPO2 was
      significantly (P < 0.05) greater in patients with diabetes than in control
      subjects, but there was no significant difference in deltaPO2 (P > 0.05) between
      patients with diabetes, with or without retinopathy. Age and deltaPO2 correlated
      significantly (P < 0.05) in control subjects but not in patients with diabetes.
      In control subjects, deltaPO2 was relatively uniform panretinally, whereas in the
      diabetic group, changes in oxygenation response were spatially inhomogeneous.
      CONCLUSIONS: These results demonstrate, for the first time, that MRI deltaPO2
      detects a significant supernormal retinal oxygenation response in patients with
      type I diabetes, even before the appearance of retinopathy. This study raises the
      possibility of using MRI measurements of deltaPO2 to monitor therapeutic efficacy
      in human trials.

PMID- 16565401
TI  - Inactivation of the Akt survival pathway during photoreceptor apoptosis in the
      retinal degeneration mouse.
AB  - PURPOSE: Previous work has indicated that the serine-threonine protein kinase Akt
      is a general mediator of cellular survival signals and that loss of Akt-mediated
      signaling can lead to the activation of apoptosis. This study was conducted to
      establish whether regulation of the Akt survival pathway mechanisms is implicated
      in the induction of apoptosis during photoreceptor cell death in the rd mouse
      model of retinal degeneration. METHODS: Quantitative Western blot analysis and
      immunocytochemistry were used to examine the activation status and localization
      of key components of the Akt signaling cascade (Akt, BAD, Forkhead [FKHR], HSP27,
      mitogen-activated protein (MAP) kinase kinase-3 and -6 (MKK3/6), the tumor
      suppressor phosphatase PTEN, and the cytoplasmic protein-tyrosine kinase cSrc
      p60), in the retina of the rd mouse in comparison with the control. The time
      points examined spanned the period of photoreceptor degeneration. RESULTS: In the
      period up to the peak of photoreceptor apoptosis at postnatal day 15,
      dysregulation of the survival pathway was identified at several levels, including
      deactivation of both Akt itself and its downstream transcription factor target
      Forkhead (FKHR) and activation of the upstream negative regulator PTEN.
      CONCLUSIONS: Taken in conjunction with previous studies, the data support a model
      in which photoreceptor cell death in the rd mouse is the result of combined
      inactivation of the Akt survival pathway and the activation of the two major
      apoptotic pathways.

PMID- 16565402
TI  - Different amino acid substitutions at the same position in rhodopsin lead to
      distinct phenotypes.
AB  - PURPOSE: Identification of a novel rhodopsin mutation in a family with retinitis
      pigmentosa and comparison of the clinical phenotype to a known mutation at the
      same amino acid position. METHODS: Screening for mutations in rhodopsin was
      performed in 78 patients with retinitis pigmentosa. All exons and flanking
      intronic regions were amplified by PCR, sequenced, and compared to the reference
      sequence derived from the National Center for Biotechnology Information (NCBI,
      Bethesda, MD) database. Patients were characterized clinically according to the
      results of best corrected visual acuity testing (BCVA), slit lamp examination
      (SLE), funduscopy, Goldmann perimetry (GP), dark adaptometry (DA), and
      electroretinography (ERG). Structural analyses of the rhodopsin protein were
      performed with the Swiss-Pdb Viewer program available on-line
      (http://www.expasy.org.spdvbv/ provided in the public domain by Swiss Institute
      of Bioinformatics, Geneva, Switzerland). RESULTS: A novel rhodopsin mutation
      (Gly90Val) was identified in a Swiss family of three generations. The pedigree
      indicated autosomal dominant inheritance. No additional mutation was found in
      this family in other autosomal dominant genes. The BCVA of affected family
      members ranged from 20/25 to 20/20. Fundus examination showed fine pigment
      mottling in patients of the third generation and well-defined bone spicules in
      patients of the second generation. GP showed concentric constriction. DA
      demonstrated monophasic cone adaptation only. ERG revealed severely reduced rod
      and cone signals. The clinical picture is compatible with retinitis pigmentosa. A
      previously reported amino acid substitution at the same position in rhodopsin
      leads to a phenotype resembling night blindness in mutation carriers, whereas
      patients reported in the current study showed the classic retinitis pigmentosa
      phenotype. The effect of different amino acid substitutions on the three
      dimensional structure of rhodopsin was analyzed by homology modeling. Distinct
      distortions of position 90 (shifts in amino acids 112 and 113) and additional
      hydrogen bonds were found. CONCLUSIONS: Different amino acid substitutions at
      position 90 of rhodopsin can lead to night blindness or retinitis pigmentosa. The
      data suggest that the property of the substituted amino acid distinguishes
      between the phenotypes.

PMID- 16565403
TI  - Immunohistochemical evidence of a melanopsin cone in human retina.
AB  - PURPOSE: Melanopsin, expressed in a subset of intrinsically photosensitive
      ganglion cells that project to the suprachiasmatic nucleus (SCN), is involved in
      the photic entrainment of circadian rhythms and other non-image-forming functions
      (pupil light reflex, masking, acute heart rate response, and alertness).
      Melanopsin has recently been shown to be a "bireactive" photopigment that
      functions as a photosensory opsin using 11-cis retinaldehyde as a chromophore and
      has intrinsic photoisomerase activity. Melanopsin is widely distributed in the
      retina of vertebrates and, depending on the species, is expressed in ganglion,
      amacrine, horizontal, and photoreceptor cells. The present study was conducted to
      determine the distribution of this opsin in the human retina. METHODS: Human
      donor eyes were obtained from donors and fixed shortly after death.
      Immunohistochemistry was used to determine melanopsin expression in the retinas
      of three donors. The possible coexpression of this photopigment with other opsins
      was studied by double-labeling immunocytochemistry and confocal analysis.
      RESULTS: In addition to the expected labeling in ganglion cells of the inner
      retinal layers, an unexpected finding showed melanopsin-immunopositive label in
      the outer segments of cones that did not coexpress other known opsins. These
      melanopsin-expressing cones are extremely sparse (5-25 cones/mm2; 0.1%-0.5% of
      the entire cone population) and are located in the peripheral retina.
      CONCLUSIONS: The presence of melanopsin in human cones suggests image and non
      image-forming roles in visual responses at both the cone input and ganglion cell
      output stages and their involvement in a broad spectrum of irradiance detection
      functions in the visual system.

PMID- 16565404
TI  - The presence of AC133-positive cells suggests a possible role of endothelial
      progenitor cells in the formation of choroidal neovascularization.
AB  - PURPOSE: Recent evidence suggests that vasculogenesis as well as angiogenesis
      occurs throughout the body during neovascularization. The recruitment of
      circulating stem cells is a key feature of vasculogenesis. The purpose of the
      present study was to determine whether markers of endothelial progenitor cells
      (EPCs) are present in choroidal neovascularization (CNV) secondary to age-related
      macular degeneration (AMD). METHODS: Surgically excised CNV (n = 9) membranes
      from patients with AMD were probed with immunohistochemical techniques using the
      following monoclonal antibodies: AC133 a putative marker of EPCs and
      hematopoietic stem cells (HSCs); the endothelial cells markers CD31, CD34, and
      von Willebrand factor (vWF); and cytokeratins and CD68, markers for retinal
      pigment epithelium (RPE) and macrophages, respectively. After secondary antibody
      amplification, reactions were visualized with fast red substrate. RESULTS: Six of
      nine specimens demonstrated cells positive for AC133 that were all found within
      predominantly cellular regions of the specimens. In the avascular fibrous stromal
      core of all specimens, the predominant cells were RPE cells and macrophages. The
      peripheral component of all CNV membranes was highly vascular and showed varying
      immunoreactivity for all endothelial markers. The greatest immunoreactivity for
      endothelial markers was observed with CD34 and vWF and least for CD31.
      CONCLUSIONS: These findings support animal studies that vasculogenesis, in
      addition to angiogenesis, may contribute to the neovascularization that occurs in
      AMD.

PMID- 16565405
TI  - Retinal pigment epithelium damage enhances expression of chemoattractants and
      migration of bone marrow-derived stem cells.
AB  - PURPOSE: To characterize chemoattractants expressed by the retinal pigment
      epithelium (RPE) after sodium iodate (NaIO3)-induced damage and to investigate
      whether ocular-committed stem cells preexist in the bone marrow (BM) and migrate
      in response to the chemoattractive signals expressed by the damaged RPE. METHODS:
      C57/BL6 mice were treated with a single intravenous injection of NaIO3 (50 mg/kg)
      to create RPE damage. At different time points real-time RT-PCR, ELISA, and
      immunohistochemistry were used to identify chemoattractants secreted in the
      subretinal space. Conditioned medium from NaIO3-treated mouse RPE was used in an
      in vitro assay to assess chemotaxis of stem cell antigen-1 positive (Sca-1+) BM
      mononuclear cells (MNCs). The expression of early ocular markers (MITF, Pax-6,
      Six-3, Otx) in migrated cells and in MNCs isolated from granulocyte colony
      stimulating factor (G-CSF) and Flt3 ligand (FL)-mobilized and nonmobilized
      peripheral blood (PB) was analyzed by real-time RT-PCR. RESULTS: mRNA for stromal
      cell-derived factor-1 (SDF-1), C3, hepatocyte growth factor (HGF), and leukemia
      inhibitory factor (LIF) was significantly increased, and higher SDF-1 and C3
      protein secretion from the RPE was found after NaIO3 treatment. A higher number
      of BMMNCs expressing early ocular markers migrated to conditioned medium from
      damaged retina. There was also increased expression of early ocular markers in
      PBMNCs after mobilization. CONCLUSIONS: Damaged RPE secretes cytokines that have
      been shown to serve as chemoattractants for BM-derived stem cells (BMSCs). Retina
      committed stem cells appear to reside in the BM and can be mobilized into the PB
      by G-CSF and FL. These stem cells may have the potential to serve as an
      endogenous source for tissue regeneration after RPE damage.

PMID- 16565406
TI  - Neuroprotective effects of D-allose against retinal ischemia-reperfusion injury.
AB  - PURPOSE: To investigate the effect of D-allose, a rare sugar, against ischemia
      reperfusion injury in the rat retina. METHODS: Retinal ischemia was induced by
      increasing intraocular pressure to 130 mm Hg and maintaining that level for 45
      minutes. Morphometric studies were performed to study the effect of D-allose on
      the histologic changes induced by ischemia in the rat retina. Glutamate release
      from the rat retina and intravitreal P(O2) profiles were monitored during and
      after ischemia with a microdialysis biosensor and oxygen-sensitive
      microelectrodes. The release of hydrogen peroxide stained with diaminobenzidine
      hydrochloride was monitored by an in vitro retinal ischemia model. RESULTS: Seven
      days after the ischemia, significant reductions in both the number of ganglion
      cells and the thickness of the inner plexiform layer were observed. Pretreatment
      with D-allose significantly inhibited the ischemic injury of the inner retina. A
      large release of glutamate occurred during the ischemia. After the recirculation,
      glutamate levels were increased again and reached a maximum in approximately 20
      minutes. The increases in extracellular glutamate during and after ischemia tend
      to be suppressed by administration of d-allose. d-Allose attenuated the increase
      in intravitreal P(O2) during reperfusion. After the ischemia, production of
      hydrogen peroxide was detected within approximately 30 minutes. D-allose
      suppressed the production of hydrogen peroxide. CONCLUSIONS: These results
      suggest that D-allose may protect neurons by decreasing extracellular glutamate
      and attenuating oxidative stress in ischemic insult.

PMID- 16565407
TI  - Ceramide is a mediator of apoptosis in retina photoreceptors.
AB  - PURPOSE: The precise mechanisms involved in photoreceptor apoptosis are still
      unclear. In the present study, the role of ceramide, a sphingolipid precursor
      that induces apoptosis on cellular stress, was investigated in relation to the
      activation of cell death in photoreceptors. METHODS: Rat retina neuronal
      cultures, with or without docosahexaenoic acid (DHA), were treated with the
      ceramide analogue acetylsphingosine (C2-ceramide), and with a glucosylceramide
      synthase inhibitor. Ceramide synthesis in cultures treated with the oxidant
      paraquat was evaluated with [3H]palmitate. The effect of inhibitors of ceramide
      de novo synthesis, fumonisin B1 and cycloserine, on photoreceptor apoptosis was
      investigated. Apoptosis, mitochondrial membrane potential, and Bcl-2 expression
      were determined. RESULTS: Addition of C2-ceramide induced photoreceptor
      apoptosis. Paraquat increased formation of [3H]ceramide in photoreceptors,
      compared with the control, whereas inhibition of ceramide synthesis, immediately
      before paraquat treatment, prevented paraquat-induced photoreceptor apoptosis.
      Fumonisin also reduced photoreceptor apoptosis during early development in vitro.
      DHA, the retina major polyunsaturated fatty acid, which protects photoreceptors
      from oxidative stress-induced apoptosis, completely blocked C2-ceramide-induced
      photoreceptor death, simultaneously increasing Bcl-2 expression. Inhibiting
      glucosylceramide synthase, which catalyzes ceramide glucosylation, before
      ceramide or paraquat treatment blocked DHA's protective effect. CONCLUSIONS: The
      results suggest that oxidative stress stimulated an increase in ceramide levels
      that induced photoreceptor apoptosis. DHA prevented oxidative stress and ceramide
      damage by upregulating Bcl-2 expression and glucosylating ceramide, thus
      decreasing its intracellular concentration. This shows for the first time that
      ceramide is a critical mediator for triggering photoreceptor apoptosis in
      mammalian retina and suggests that modulating ceramide levels may provide a
      therapeutic tool for preventing photoreceptor death in neurodegenerative
      diseases.

PMID- 16565408
TI  - A frameshift mutation in RPGR exon ORF15 causes photoreceptor degeneration and
      inner retina remodeling in a model of X-linked retinitis pigmentosa.
AB  - PURPOSE: To characterize the course of retinal disease in X-linked progressive
      retinal atrophy 2 (XLPRA2), a canine model of early onset X-linked retinitis
      pigmentosa (XLRP) caused by a two-nucleotide microdeletion in RPGR ORF15.
      METHODS: The retinas of 25 XLPRA2-affected dogs (age range, 2-40.6 weeks) and age
      matched control subjects were collected, fixed, and embedded in epoxy resin for
      morphologic evaluation or in optimal cutting temperature (OCT) medium for TUNEL
      assay and immunohistochemistry. Cell-specific antibodies were used to examine
      changes in rods and cones and to evaluate the effects of the primary
      photoreceptor degeneration on inner retinal cells. RESULTS: Abnormal development
      of photoreceptors was recognizable as early as 3.9 weeks of age. Outer segment
      (OS) misalignment was followed by their disorganization and fragmentation.
      Reduction in length and broadening of rod and cone inner segments (IS) was next
      observed, followed by the focal loss of rod and cone IS at later time points. The
      proportion of dying photoreceptors peaked at approximately 6 to 7 weeks of age
      and was significantly reduced after 12 weeks. In addition to rod and cone opsin
      mislocalization, there was early rod neurite sprouting, retraction of rod bipolar
      cell dendrites, and increased Muller cell reactivity. Later in the course of the
      disease, changes were also noted in horizontal cells and amacrine cells.
      CONCLUSIONS: XLPRA2 is an early-onset model of XLRP that is morphologically
      characterized by abnormal photoreceptor maturation followed by progressive rod
      cone degeneration and early inner retina remodeling. The results suggest that
      therapeutic strategies for this retinal degeneration should target not solely
      photoreceptor cells but also inner retinal neurons.

PMID- 16565410
TI  - Activation of signaling pathways and stress-response genes in an experimental
      model of retinal detachment.
AB  - PURPOSE: Despite the high metabolic demands of the neural retina, its detachment
      from the retinal pigment epithelium does not lead to immediate death for most of
      the cells. This study was undertaken to test the hypothesis that intrinsic
      protective mechanisms are activated in the neural retina during early stages of
      retinal detachment. METHODS: Retinal detachments were created in Brown Norway
      rats by injection of 1% hyaluronic acid into the subretinal space. Gene
      expression profiles of retinas detached for 24 hours were generated with a gene
      microarray (rat U34 GeneChips; Affymetrix, Santa Clara, CA) and compared to the
      profiles from control attached retinas in a robust multiarray protocol and false
      discovery-rate analysis. Changes in individual, differentially expressed genes
      were validated by quantitative real-time polymerase chain reaction (qRT-PCR)
      analysis. Additional qRT-PCR and immunoblot analyses were performed for
      additional selected genes. RESULTS: Genome-wide expression profiling revealed 27
      genes that are differentially expressed in retinas detached for 24 hours. In
      silico analysis and functional clustering suggested that most genes belonged to
      three signaling pathways: interleukin-6/STAT, transforming growth factor
      beta/Smad, and aryl hydrocarbon receptor oxidative stress response. Additional
      analyses of selected genes from these pathways demonstrated a time-dependent
      increase in their expression in detached retinas. CONCLUSIONS: Retinal detachment
      results in the early activation of stress-response genes and specific signaling
      pathways. This adaptive response may enable the photoreceptor cells to survive
      the acute phase of a retinal detachment, and it is the breakdown of these
      protective mechanisms in chronic disease that leads to the ultimate death of the
      cell.

PMID- 16565409
TI  - Expression of the gamma-aminobutyric acid (GABA) plasma membrane transporter-1 in
      monkey and human retina.
AB  - PURPOSE: To determine the expression pattern of the predominant gamma
      aminobutyric acid (GABA) plasma membrane transporter GAT-1 in Old World monkey
      (Macaca mulatta) and human retina. METHODS: GAT-1 was localized in retinal
      sections by using immunohistochemical techniques with fluorescence and confocal
      microscopy. Double-labeling studies were performed with the GAT-1 antibody using
      antibodies to GABA, vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase
      (TH), and the bipolar cell marker Mab115A10. RESULTS: The pattern of GAT-1
      immunostaining was similar in human and monkey retinas. Numerous small
      immunoreactive somata were in the inner nuclear layer (INL) and were present
      rarely in the inner plexiform layer (IPL) of all retinal regions. Medium GAT-1
      somata were in the ganglion cell layer in the parafoveal and peripheral retinal
      regions. GAT-1 fibers were densely distributed throughout the IPL. Varicose
      processes, originating from both the IPL and somata in the INL, arborized in the
      outer plexiform layer (OPL), forming a sparse network in all retinal regions,
      except the fovea. Sparsely occurring GAT-1 processes were in the nerve fiber
      layer in parafoveal regions and near the optic nerve head but not in the optic
      nerve. In the INL, 99% of the GAT-1 somata contained GABA, and 66% of the GABA
      immunoreactive somata expressed GAT-1. GAT-1 immunoreactivity was in all VIP
      containing cells, but it was absent in TH-immunoreactive amacrine cells and in
      Mab115A10 immunoreactive bipolar cells. CONCLUSIONS: GAT-1 in primate retinas is
      expressed by amacrine and displaced amacrine cells. The predominant expression of
      GAT-1 in the inner retina is consistent with the idea that GABA transporters
      influence neurotransmission and thus participate in visual information processing
      in the retina.

PMID- 16565412
TI  - Perifoveal function in patients with North Carolina macular dystrophy: the
      importance of accounting for fixation locus.
AB  - PURPOSE: To quantify the extent of visual function losses in patients with North
      Carolina Macular Dystrophy (NCMD) and to demonstrate the importance of accounting
      for eccentric fixation when making comparisons with normal data. METHODS: Five
      patients with NCMD who were from a single family were examined. Multifocal
      electroretinograms (mfERGs) and psychophysical assessments of acuity and
      luminance visual field sensitivities were measured throughout the central retina.
      Comparisons of responses from equivalent retinal areas were accomplished by
      shifting normal templates to be centered at the locus of fixation for each
      patient. RESULTS: Losses of psychophysically measured visual function in patients
      with NCMD extend to areas adjacent to the locations of visible lesions. The
      multifocal ERG amplitude was reduced only within the area of visible lesion.
      Multifocal ERG implicit times were delayed throughout the entire central retinal
      area assessed. CONCLUSIONS: ERG timing is a sensitive assay of retinal function,
      and our results indicate that NCMD has a widespread effect at the level of the
      mid and outer retina. The findings also demonstrated that it is necessary to
      account for fixation locus and to ensure that equivalent retinal areas are
      compared when testing patients with macular disease who have eccentric fixation.

PMID- 16565411
TI  - Retinal pigment epithelium protection from oxidant-mediated loss of MMP-2
      activation requires both MMP-14 and TIMP-2.
AB  - PURPOSE: Eyes with age-related macular degeneration (AMD) demonstrate
      accumulation of specific deposits and extracellular matrix (ECM) molecules under
      the retinal pigment epithelium (RPE). Metalloproteinases (MMP) are crucial
      regulators of basement membrane and ECM turnover. Accordingly, loss of RPE MMP
      activity most likely leads to excessive accumulation of collagen and other ECM, a
      potential mechanism for formation of deposits. A prior study showed that MMP-2
      activity, but not pro-MMP-2 protein, decreases after RPE oxidative injury,
      indicating that oxidant injury disrupts the enzymatic cleavage of pro-MMP-2.
      Activation of MMP-2 requires the formation of a tri-molecular complex of pro-MMP
      2, MMP-14, and tissue inhibitor of metalloproteinases (TIMP)-2. Therefore, a
      study was conducted to investigate the impact of oxidant injury on the
      interaction between these three molecules. METHODS: Human GFP-RPE cells were
      oxidant injured by transient exposure to H2O2 and myeloperoxidase, and the time
      course of recovery determined. Supernatants and cell lysates were collected for
      analysis of MMP-2, MMP-14, and TIMP-2 activity, mRNA and protein expression. In
      some studies, overexpression with either MMP-14 or TIMP-2 was performed to revert
      the cells to a preinjury phenotype. RESULTS: Transient injury resulted in a
      decrease of both MMP-14 and TIMP-2 activity and protein. Overexpression of each
      single molecule failed to prevent the injury-induced decrease of MMP-2 activity.
      In contrast, overexpression of MMP-14 together with the addition of exogenous
      TIMP-2 prevented the reduction of MMP-2 activation. CONCLUSIONS: Loss of MMP-2
      activity after oxidant injury is caused by the downregulation of MMP-14 and TIMP
      2. Overexpression of either MMP-14 or TIMP-2 alone before oxidant injury is not
      enough to prevent loss of MMP-2 activity. All three components of the tri
      molecular complex must be present to preserve normal MMP-2 activity after oxidant
      injury.

PMID- 16565413
TI  - Comparison of the retinal image quality with a Hartmann-Shack wavefront sensor
      and a double-pass instrument.
AB  - PURPOSE: Wavefront sensors provide quite useful information on the optical
      quality of the eye. However, in eyes where very high-order aberrations and
      scattered light are prominent, wavefront sensors may overestimate retinal image
      quality. This study showed that, in those cases, the double-pass technique is a
      complementary tool for better estimation of ocular optical quality. METHODS: A
      double-pass (DP) instrument was used, based on recording images of a point source
      in near-infrared light after reflection in the retina and double-pass through the
      ocular media. The aberrations were also measured with a prototype of near
      infrared Hartmann-Shack (HS) wavefront sensor adapted to the clinical
      environment. From the wave aberrations, the modulation transfer function (MTF)
      was calculated (MTF_HS). The MTF was also obtained from the double-pass images
      (MTF_DP). Both techniques were applied in normal young subjects as the control
      and in three other groups of eyes: older subjects, after LASIK refractive
      surgery, and after IOL implantation. RESULTS: The MTFs obtained from DP and HS
      techniques were compared. In the group of normal eyes with low levels of
      intraocular scattering, these estimates were quite similar, indicating that both
      techniques captured well most of the optical degradation. However, in eyes where
      scatter was more predominant (e.g., early cataract, posterior capsular
      opacification after IOL implantation) the MTF provided by the HS sensor was
      always higher than the MTF obtained from DP. A single parameter was used to
      indicate the differences. CONCLUSIONS: In eyes with low scattering, DP and HS
      techniques provided similar estimates of the retinal image quality. However, in a
      patient's eye with mild to severe amount of scatter, wavefront sensors might
      overestimate image quality, whereas the DP technique produces a more accurate
      description of the optical quality, better correlated with the quality of vision.

PMID- 16565415
TI  - Vascular endothelial growth factor and hepatocyte regeneration in acetaminophen
      toxicity.
AB  - VEGF or VEGF-A is a major regulator of angiogenesis and has been recently shown
      to be important in organ repair. The potential role of VEGF in acetaminophen
      (APAP)-induced hepatotoxicity and recovery was investigated in B6C3F1 male mice.
      Mice were treated with APAP (300 mg/kg ip) and killed at various time points that
      reflect both the acute and recovery stages of toxicity. VEGF-A protein levels
      were increased 7-fold at 8 h and followed the development of hepatotoxicity. VEGF
      receptor 1, 2, and 3 (VEGFR1, VEGFR2, and VEGFR3, respectively) expression
      increased throughout the time course, with maximal expression at 48, 8, and 72 h,
      respectively. Treatment with the VEGF receptor inhibitor SU5416 (25 mg/kg ip at 3
      h) had no effect on toxicity at 6 or 24 h. In further studies, the role of SU5416
      on the late stages of toxicity was examined. Treatment of mice with APAP and
      SU5416 (25 mg/kg ip at 3 h) resulted in decreased expression of PCNA, a marker of
      cellular proliferation. Expression of platelet endothelial cell adhesion
      molecule, a measure of small vessel density, and endothelial nitric oxide
      synthase (NOS), a downstream target of VEGFR2, were increased at 48 and 72 h
      following toxic doses of APAP, and treatment with SU5416 decreased their
      expression. These data indicate that endogenous VEGF is critically important to
      the process of hepatocyte regeneration in APAP-induced hepatotoxicity in the
      mouse.

PMID- 16565414
TI  - Yeast initiator tRNA identity elements cooperate to influence multiple steps of
      translation initiation.
AB  - All three kingdoms of life employ two methionine tRNAs, one for translation
      initiation and the other for insertion of methionines at internal positions
      within growing polypeptide chains. We have used a reconstituted yeast translation
      initiation system to explore the interactions of the initiator tRNA with the
      translation initiation machinery. Our data indicate that in addition to its
      previously characterized role in binding of the initiator tRNA to eukaryotic
      initiation factor 2 (eIF2), the initiator-specific A1:U72 base pair at the top of
      the acceptor stem is important for the binding of the eIF2.GTP.Met-tRNA(i)
      ternary complex to the 40S ribosomal subunit. We have also shown that the
      initiator-specific G:C base pairs in the anticodon stem of the initiator tRNA are
      required for the strong thermodynamic coupling between binding of the ternary
      complex and mRNA to the ribosome. This coupling reflects interactions that occur
      within the complex upon recognition of the start codon, suggesting that these
      initiator-specific G:C pairs influence this step. The effect of these anticodon
      stem identity elements is influenced by bases in the T loop of the tRNA,
      suggesting that conformational coupling between the D-loop-T-loop substructure
      and the anticodon stem of the initiator tRNA may occur during AUG codon selection
      in the ribosomal P-site, similar to the conformational coupling that occurs in A
      site tRNAs engaged in mRNA decoding during the elongation phase of protein
      synthesis.

PMID- 16565417
TI  - Molecular, functional, and pharmacological targets for the development of gut
      promotility drugs.
AB  - The science of gastrointestinal motility has made phenomenal advances during the
      last fifty years. Yet, there is a paucity of effective promotility drugs to treat
      functional bowel disorders that affect 10-29% of the U.S. population. A part of
      the reason for the lack of effective drugs is our limited understanding of the
      etiology of these diseases. In the absence of this information, mostly an ad hoc
      approach has been used to develop the currently available drugs, which are
      modestly effective or effective in only a subset of the patients with functional
      bowel disorders. This review discusses a grounds-up approach for development of
      the next generation of promotility drugs. The approach is based on our current
      understanding of 1) the different types of contractions that produce overall
      motility function of mixing and orderly net distal propulsion in major gut
      organs, 2) the regulatory mechanisms of these contractions, 3) which receptors
      and intracellular signaling molecules could be targeted to stimulate specific
      types of contractions to accelerate or retard transit, and 4) the strengths and
      limitations of animal models and experimental approaches that could screen
      potential promotility drugs for their efficacy in human gut propulsion in
      functional bowel disorders.

PMID- 16565416
TI  - Geldanamycin prevents hemorrhage-induced ATP loss by overexpressing inducible
      HSP70 and activating pyruvate dehydrogenase.
AB  - Hemorrhage in mice results in decreased ATP levels in the jejunum, lung, kidney,
      heart, and brain but not in liver tissue lysates, albeit at variable levels and
      time kinetics. The decreased protein expression and activity of pyruvate
      dehydrogenase (PDH) accounted for the hemorrhage-induced ATP loss. Treatment with
      geldanamycin (GA; 1 microg/g body wt), a known inducer of heat shock protein
      (HSP)70, inhibited the hemorrhage-induced ATP loss in the jejunum, lung, heart,
      kidney, and brain. GA was found to increase PDH protein, preserve PDH enzymatic
      activity, and inhibit mucosal injury in jejunum tissues. GA-induced HSP70i was
      found to form complexes with PDH protein. HSP70 gene transfer into intestinal
      epithelial cells promoted PDH and ATP levels, whereas HSP70 short interfering RNA
      limited them. We conclude that agents able to increase the expression of HSP70
      and PDH may be of value in reducing pathology resulting from hemorrhage
      associated ATP loss.

PMID- 16565418
TI  - Experimental colitis modulates the functional properties of NMDA receptors in
      dorsal root ganglia neurons.
AB  - N-methyl-D-aspartate (NMDA) receptors (NMDARs) on spinal afferent neurons
      regulate the peripheral and central release of neuropeptides involved in the
      development of hyperalgesia. We examined the effect of experimental colitis on
      the molecular and functional properties of NMDARs on these neurons. Lumbosacral
      dorsal root ganglia (DRG) were collected from adult rats 5 days after the
      induction of colitis for whole cell patch-clamp recording, Western blot analysis,
      and quantitative RT-PCR. Compared with neurons from control rats, those taken
      from animals with colitis had a threefold higher density of NMDA currents in both
      retrograde-labeled, colon-specific, and unlabeled DRG neurons. Increased current
      densities were not observed in DRG neurons taken from thoracic spinal levels.
      There was no significant change in NMDA or glycine affinity or in voltage
      dependent Mg2+ inhibition; however, there was a 10-fold decrease in sensitivity
      to the NR2B subunit-selective antagonist ifenprodil. Quantitative RT-PCR and
      Western blot analysis indicated a 28% increase in the expression of NR2B with
      little or no change in the other three NR2 subunits. The addition of the Src
      family tyrosine kinase inhibitor PP2 (10 microM) decreased NMDAR currents in
      neurons from colitis but not control rats. Conversely, pretreatment of DRG
      neurons from control animals with 100 microM sodium orthovanadate increased NMDAR
      currents and decreased ifenprodil sensitivity to levels similar to those observed
      in neurons from animals with colitis. In conclusion, colonic inflammation
      upregulates the activity of NMDARs in all DRG neurons within ganglia innervating
      this tissue through mechanisms involving increased expression and persistent
      tyrosine phosphorylation.

PMID- 16565420
TI  - Antibodies in the small intestine: mucosal synthesis and deposition of anti
      glycosyl IgA, IgM, and IgG in the enterocyte brush border.
AB  - Synthesis and deposition of immunoglobulins in the brush border was studied in
      organ-cultured pig small intestinal mucosal explants. Surprisingly, comparable
      amounts of IgM and IgA were synthesized during a 6-h pulse, and also newly made
      IgG was detected in media and explants, including the microvillar fraction. For
      IgA and IgM, this subcellular distribution is consistent with basolateral-to
      apical transcytosis, mediated by the polymeric immunoglobulin receptor. IgG is a
      ligand for the Fc receptor FcRn, and beta2-microglobulin, the light chain of
      FcRn, coclustered in immunogold double labeling with IgG in subapical endosomes
      and in the basolateral membrane of enterocytes. In addition, beta2-microglobulin
      was copurified with IgG on protein G-Sepharose. Apical endocytosis of IgG, as
      judged by internalization of fluorescent protein G, was not detectable except in
      a few isolated cells. This suggests that IgG in the adult small intestine is
      transported across the enterocyte mainly in the basolateral to apical direction.
      Significant fractions of all immunoglobulins bound to lactoseagarose, indicating
      that "anti-glycosyl" antibodies, raised against commensal gut bacteria, are
      synthesized locally in the small intestine. By partial deposition in the brush
      border, these antibodies therefore may have a protective function by preventing
      lectin-like pathogens from gaining access to the brush border surface.

PMID- 16565419
TI  - Distinct requirements for Hfe in basal and induced hepcidin levels in iron
      overload and inflammation.
AB  - Hepcidin is a negative regulator of iron absorption produced mainly by the liver
      in response to changes in iron stores and inflammation, and its levels have been
      shown to regulate the intestinal basolateral iron transporter ferroportin1 (Fp1).
      Hereditary hemochromatosis patients and Hfe-deficient mice show inappropriate
      expression of hepcidin but, in apparent contradiction, still retain the ability
      to regulate iron absorption in response to alterations of iron metabolism. To
      further understand the molecular relationships among Hfe, hepcidin, and Fp1, we
      investigated hepcidin and Fp1 regulation in Hfe-deficient mice (Hfe-/- and beta2m
      /-) in response to iron deprivation, iron loading, and acute inflammation. We
      found that whereas basal hepcidin levels were manifestly dependent on the
      presence of Hfe and on the mouse background, all Hfe-deficient mice were still
      able to regulate hepcidin in situations of altered iron homeostasis. In the
      liver, Fp1 was modulated in opposite directions by iron and LPS, and its
      regulation in Hfe-deficient mice was similar to that observed in wild-type mice.
      In addition, we found that iron-deprived mice were able to mount a robust
      response after LPS challenge and that Toll-like receptor 4 (TLR-4)-deficient mice
      fail to regulate hepcidin expression in response to LPS. In conclusion, these
      results suggest that although Hfe is necessary for the establishment of hepcidin
      basal levels, it is dispensable for hepcidin regulation through both the iron
      sensing and inflammatory pathways, and hepatic Fp1 regulation is largely
      independent of hepcidin and Hfe. The inflammatory pathway overrides the iron
      sensing pathway and is TLR-4 dependent.

PMID- 16565422
TI  - ATS workshop proceedings: exhaled nitric oxide and nitric oxide oxidative
      metabolism in exhaled breath condensate.

PMID- 16565423
TI  - The biological chemistry of nitric oxide as it pertains to the extrapulmonary
      effects of inhaled nitric oxide.
AB  - The chemical properties of nitric oxide (NO) have been studied for over 200
      years. However, it is only within the last 20 years that the biological
      implications of this chemistry have been considered. The classical model of NO
      action within the vasculature centers on production in the endothelium, diffusion
      to the smooth muscle, and subsequent activation of guanylate cyclase via binding
      to its heme iron. In the context of this model, it is difficult to conceptualize
      extrapulmonary effects of inhaled NO. However, NO possesses complex redox
      chemistry and is capable of forming a range of nitrogen oxide species and is
      therefore capable of interacting with a variety of biomolecules. Of particular
      interest is its reaction with reduced cysteine to form an S-nitrosothiol (SNO).
      SNOs are formed throughout NO biology and are a post-translational modification
      that has been shown to regulate many proteins under physiologic conditions.
      Hemoglobin, which was considered to be solely a consumer of NO, can form SNO in a
      conformationally dependent manner, which allows for the transport of inhaled NO
      beyond the realm of the lung. Higher oxides of nitrogen are capable of modifying
      proteins via nitration of tyrosines, which has been shown to occur under
      pathologic conditions. By virtue of its redox reactivity, one can appreciate that
      inhaled NO has a variety of routes by which it can act and that these routes may
      lead to extrapulmonary effects.

PMID- 16565426
TI  - Regulation of respiration and endothelial gene expression by S-nitrosothiols in
      health and disease.
AB  - The effects of nitric oxide (NO) are mediated by cyclic guanosine monophosphate
      (cGMP)-dependent and cGMP-independent processes. Most cGMP-independent effects
      are mediated by the actions of S-nitrosothiols (SNOs). SNOs have been shown to
      play a role in health and in disease. In studies performed in the mouse and rat,
      the ventilatory response to hypoxia is regulated in the nucleus tractus
      solitarius by SNOs exported from red blood cells. This may affect the treatment
      of respiratory distress in newborns and sleep apnea in adults. Likewise, SNOs
      have been shown to alter the stability and abundance of the transcription factor
      hypoxia inducible factor-1, altering the expression of hypoxia-regulated genes.
      Identification of the proteins involved in these signaling events will lead to
      new therapeutic approaches in the treatment of diseases characterized by limited
      oxygen availability.

PMID- 16565427
TI  - Summary: systemic effects of inhaled nitric oxide.
AB  - Many effects of inhaled nitric oxide (NO) are not explained by the convention
      that NO activates pulmonary guanylate cyclase or is inactivated by ferrous deoxy-
      or oxyheme. Inhaled NO can affect blood flow to a variety of systemic vascular
      beds, particularly under conditions of ischemia/reperfusion. It affects leukocyte
      adhesion and rolling in the systemic periphery. Inhaled NO therapy can overcome
      the systemic effects of NO synthase inhibition. In many cases, these systemic-NO
      synthase-mimetic effects of inhaled NO seem to involve reactions of NO with
      circulating proteins followed by transport of NO equivalents from the lung to the
      systemic periphery. The NO transfer biology associated with inhaled NO therapy is
      rich with therapeutic possibilities. In this article, many of the whole-animal
      studies regarding the systemic effects of inhaled NO are reviewed in the context
      of this emerging understanding of the complexities of NO biochemistry.

PMID- 16565428
TI  - Why does the lung hyperinflate?
AB  - Patients with chronic obstructive pulmonary disease (COPD) often have some degree
      of hyperinflation of the lungs. Hyperinflated lungs can produce significant
      detrimental effects on breathing, as highlighted by improvements in patient
      symptoms after lung volume reduction surgery. Measures of lung volumes correlate
      better with impairment of patient functional capabilities than do measures of
      airflow. Understanding the mechanisms by which hyperinflation occurs in COPD
      provides better insight into how treatments can improve patients' health. Both
      static and dynamic processes can contribute to lung hyperinflation in COPD.
      Static hyperinflation is caused by a decrease in elasticity of the lung due to
      emphysema. The lungs exert less recoil pressure to counter the recoil pressure of
      the chest wall, resulting in an equilibrium of recoil forces at a higher resting
      volume than normal. Dynamic hyperinflation is more common and can occur
      independent of or in addition to static hyperinflation. It results from air being
      trapped within the lungs after each breath due to a disequilibrium between the
      volumes inhaled and exhaled. The ability to fully exhale depends on the degree of
      airflow limitation and the time available for exhalation. These can both vary,
      causing greater hyperinflation during exacerbations or increased respiratory
      demand, such as during exercise. Reversibility of dynamic hyperinflation offers
      the possibility for intervention. Use of bronchodilators with prolonged durations
      of action, such as tiotropium, can sustain significant reductions in lung
      inflation similar in effect to lung volume reduction surgery. How efficacy of
      bronchodilators is assessed may, therefore, need to be reevaluated.

PMID- 16565425
TI  - Immunoregulatory and antimicrobial effects of nitrogen oxides.
AB  - The therapeutic effects of inhaled nitric oxide (NO) therapy are thought to be
      restricted to the pulmonary vasculature because of rapid inactivation of NO by
      hemoglobin in the bloodstream. However, recent data suggest that inhaled NO may
      not only be scavenged by the heme iron of hemoglobin but also may react with
      protein thiols in the bloodstream, including cysteine-93 of the hemoglobin B
      subunit. Reaction of NO with protein or peptide thiols is termed S-nitrosylation
      and results in the formation of relatively stable protein S-nitrosothiols that
      carry NO bioactivity to distal organs. Thus, inhaled NO-induced protein S
      nitrosylation may allow inhaled NO to have multiple as yet undiscovered
      physiologic and pathophysiologic effects outside of the lung. Here we review the
      immunoregulatory and antimicrobial functions of NO and the potential effects of
      inhaled NO therapy on host defense.

PMID- 16565424
TI  - Extrapulmonary effects of inhaled nitric oxide: role of reversible S
      nitrosylation of erythrocytic hemoglobin.
AB  - Early applications of inhaled nitric oxide (iNO), typically in the treatment of
      diseases marked by acute pulmonary hypertension, were met by great enthusiasm
      regarding the purported specificity of iNO: vasodilation by iNO was specific to
      the lung (without a change in systemic vascular resistance), and within the lung,
      NO activity was said to be confined spatially and temporally by Hb within the
      vascular lumen. Underlying these claims were classical views of NO as a short
      lived paracrine hormone that acts largely through the heme groups of soluble
      guanylate cyclase, and whose potential activity is terminated on encountering the
      hemes of red blood cell (RBC) Hb. These classical views are yielding to a broader
      paradigm, in which NO-related signaling is achieved through redox-related NO
      adducts that endow NO synthase products with the ability to act at a distance in
      space and time from NO synthase itself. Evidence supporting the biological
      importance of such stable NO adducts is probably strongest for S-nitrosothiols
      (SNOs), in which NO binds to critical cysteine residues in proteins or peptides.
      The circulating RBC is a major SNO reservoir, and RBC Hb releases SNO-related
      bioactivity peripherally on O2 desaturation. These new paradigms describing NO
      transport also provide a plausible mechanistic understanding of the increasingly
      recognized peripheral effects of inhaled NO. An explanation for the peripheral
      actions of inhaled NO is discussed here, and the rationale and results of
      attempts to exploit the "NO delivery" function of the RBC are reviewed.

PMID- 16565429
TI  - Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive
      pulmonary disease.
AB  - Expiratory flow limitation is the pathophysiologic hallmark of chronic
      obstructive pulmonary disease (COPD), but dyspnea (breathlessness) is its most
      prominent and distressing symptom. Acute dynamic lung hyperinflation, which
      refers to the temporary increase in operating lung volumes above their resting
      value, is a key mechanistic consequence of expiratory flow limitation, and has
      serious mechanical and sensory repercussions. It is associated with excessive
      loading and functional weakness of inspiratory muscles, and with restriction of
      normal VT expansion during exercise. There is a strong correlation between the
      intensity of dyspnea at a standardized point during exercise, the end-expiratory
      lung volume, and the increased ratio of inspiratory effort to volume displacement
      (i.e., esophageal pressure relative to maximum: Vt as a % of predicted VC). This
      increased effort-displacement ratio in COPD crudely reflects the neuromechanical
      dissociation of the respiratory system that arises as a result of hyperinflation.
      The corollary of this is that any intervention that reduces end-expiratory lung
      volume will improve effort-displacement ratios and alleviate dyspnea. In flow
      limited patients, bronchodilators act by improving dynamic airway function, thus
      enhancing lung emptying and reducing lung hyperinflation. Long-acting
      bronchodilators have recently been shown to reduce hyperinflation during both
      rest and exercise in moderate to severe COPD. This lung deflation allows greater
      Vt expansion for a given inspiratory effort during exercise with consequent
      improvement in dyspnea and exercise endurance.

PMID- 16565430
TI  - Reduction of hyperinflation by pharmacologic and other interventions.
AB  - Hyperinflation of the lungs is associated with activity limitation and reduced
      quality of life of patients with chronic obstructive pulmonary disease (COPD).
      Cardiopulmonary exercise testing has proven useful, not only in establishing this
      link, but also in determining which interventions modify exercise endurance and
      the mechanisms by which this is achieved. In COPD, dynamic hyperinflation is
      reduced during exercise by interventions that either increase the potential for
      expiratory flow or increase the time available for expiration. Two classes of
      intervention improve exercise tolerance by increasing expiratory flow.
      Bronchodilators reduce expiratory airflow resistance by increasing the diameter
      of the airways. An alternative intervention, though less practical, is to reduce
      the density of the gas exhaled through obstructed airways, such as occurs when
      breathing a mixture of helium and oxygen (heliox). In contrast, supplemental
      oxygen and exercise rehabilitation programs improve endurance by reducing
      respiratory ventilatory drive and, therefore, respiratory rate. The different
      mechanisms exploited by these interventions to reduce dynamic hyperinflation
      suggest that combination treatments should yield additive benefits. This has been
      proven in the case of combinations of rehabilitative exercise training with
      supplemental oxygen, or with the bronchodilator tiotropium, both of which have
      been found to yield additive effects. With such interventions, we already have
      options for improving the mobility of patients with COPD. With a firm
      understanding of the physiologic basis of exercise limitation, we can focus on
      defining new and better strategies to improve exercise tolerance.

PMID- 16565431
TI  - Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia.
AB  - Hypoxia is one of the most frequently encountered stresses in health and disease.
      The duration, frequency, and severity of hypoxic episodes are critical factors
      determining whether hypoxia is beneficial or harmful. Adaptation to intermittent
      hypoxia has been demonstrated to confer cardiovascular protection against more
      severe and sustained hypoxia, and, moreover, to protect against other stresses,
      including ischemia. Thus, the direct and cross protective effects of adaptation
      to intermittent hypoxia have been used for treatment and prevention of a variety
      of diseases and to increase efficiency of exercise training. Evidence is mounting
      that nitric oxide (NO) plays a central role in these adaptive mechanisms. NO
      dependent protective mechanisms activated by intermittent hypoxia include
      stimulation of NO synthesis as well as restriction of NO overproduction. In
      addition, alternative, nonenzymic sources of NO and negative feedback of NO
      synthesis are important factors in optimizing NO concentrations. The adaptive
      enhancement of NO synthesis and/or availability activates or increases expression
      of other protective factors, including heat shock proteins, antioxidants and
      prostaglandins, making the protection more robust and sustained. Understanding
      the role of NO in mechanisms of adaptation to hypoxia will support development of
      therapies to prevent and treat hypoxic or ischemic damage to organs and cells and
      to increase adaptive capabilities of the organism.

PMID- 16565432
TI  - Bacteriophage endolysins as a novel class of antibacterial agents.
AB  - Endolysins are double-stranded DNA bacteriophage-encoded peptidoglycan hydrolases
      produced in phage-infected bacterial cells toward the end of the lytic cycle.
      They reach the peptidoglycan through membrane lesions formed by holins and cleave
      it, thus, inducing lysis of the bacterial cell and enabling progeny virions to be
      released. Endolysins are also capable of degrading peptidoglycan when applied
      externally (as purified recombinant proteins) to the bacterial cell wall, which
      also results in a rapid lysis of the bacterial cell. The unique ability of
      endolysins to rapidly cleave peptidoglycan in a generally species-specific manner
      renders them promising potential antibacterial agents. Originally developed with
      a view to killing bacteria colonizing mucous membranes (with the first report
      published in 2001), endolysins also hold promise for the treatment of systemic
      infections. As potential antibacterials, endolysins possess several important
      features, for instance, a novel mode of action, a narrow antibacterial spectrum,
      activity against bacteria regardless of their antibiotic sensitivity, and a low
      probability of developing resistance. However, there is only one report directly
      comparing the activity of an endolysin with that of an antibiotic, and no general
      conclusions can be drawn regarding whether lysins are more effective than
      traditional antibiotics. The results of the first preclinical studies indicate
      that the most apparent potential problems associated with endolysin therapy
      (e.g., their immunogenicity, the release of proinflammatory components during
      bacteriolysis, or the development of resistance), in fact, may not seriously
      hinder their use. However, all data regarding the safety and therapeutic
      effectiveness of endolysins obtained from preclinical studies must be ultimately
      verified by clinical trials. This review discusses the prophylactic and
      therapeutic applications of endolysins, especially with respect to their
      potential use in human medicine. Additionally, we outline current knowledge
      regarding the structure and natural function of the enzymes in phage biology,
      including the most recent findings.

PMID- 16565433
TI  - Iron restriction negatively affects bone in female rats and mineralization of
      hFOB osteoblast cells.
AB  - We previously reported that severe iron deficiency negatively affects bone
      microarchitecture. Here we determined whether marginal iron restriction that
      reflects some human consumption patterns could have similar consequences. Thirty
      two weanling female rats were randomly divided into four groups and fed the
      following diets for 10 weeks: (i) iron-adequate, calcium-adequate (FeA:CaA), (ii)
      calcium-restricted (FeA:CaR), (iii) iron-restricted (FeR:CaA), and (iv) both
      calcium- and iron-restricted (FeR:CaR) diets. DEXA analysis revealed that CaR
      decreased bone mineral density (BMD), and FeR decreased whole-body bone mineral
      content (BMC). Iron-restricted and calcium-restricted groups had lower BMD than
      did their adequate counterparts. All treatment-restricted groups had lower BMD in
      the fourth lumbar (L-4) vertebrae than the FeA:CaA group. Vertebrae BMD was lower
      in all treatment groups compared to the control group, and for BMC, the CaR
      groups were lower than the CaA groups and the FeR groups were lower that the FeA
      groups, and BMC were lower in iron- and calcium-restricted groups. The
      microarchitecture of the L-4 vertebrae was compromised in FeA:CaR, FeR:CaA, and
      FeR:CaR: (i) the connectivity density was reduced by FeR and by CaR; and (ii)
      trabecular number was decreased and trabecular separation was increased by FeR.
      Cortical thickness of the femur was reduced by both FeR and CaR. Finite element
      analysis revealed that L-4 vertebrae from the FeR:CaA group had greater internal
      stress with an applied force than the FeA:CaA group and, thus, would be more
      likely to break. Chelation of iron in cultured osteoblast cells impaired
      mineralization but had no impact upon Type I collagen deposition. Iron depletion,
      similar to that occurring among some human populations, reduced bone strength and
      microarchitecture based on the in vivo and in vitro results reported here.
      Impaired mineralization with iron depletion appears to be a possible mechanism
      for the observed bone abnormalities.

PMID- 16565434
TI  - Vagotonic effects of enkephalin are not mediated by sympatholytic mechanisms.
AB  - This study examined the hypothesis that vagotonic and sympatholytic effects of
      cardiac enkephalins are independently mediated by different receptors. A dose
      response was constructed by administering the delta-receptor opioid methionine
      enkephalin-arginine-phenylalanine (MEAP) by microdialysis into the interstitium
      of the canine sinoatrial node during vagal and sympathetic stimulation. The right
      cardiac sympathetic nerves were stimulated as they exited the stellate ganglion
      at frequencies selected to increase heart rate approximately 35 bpm. The right
      cervical vagus was stimulated at frequencies selected to produce a two-step
      decline in heart rate of 25 and 50 bpm. A six-step dose-response was constructed
      by recording heart rates during nerve stimulation as the dose of MEAP was
      increased between 0.05 pmol/min and 1.5 nmol/min. Vagal transmission improved
      during MEAP at 0.5 pmol/min. However, sympathetically mediated tachycardia was
      unaltered with any dose of MEAP. In Study 2, a similar dose-response was
      constructed with the kappa-opioid receptor agonist trans(+/-)-3-4-dichloro-N
      methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide-HCl (U-50488H) to
      illustrate an independent sympatholytic effect and to verify its kappa-receptor
      character. U-50488H gradually suppressed the sympathetic tachycardia, with a
      significant effect obtained only at the highest dose (1.5 nmol/min). U-50488H had
      no effect on vagally mediated bradycardia. Surprisingly, the sympatholytic effect
      was not reversed by withdrawing U-50488H or by the subsequent addition of the
      kappa-antagonist 17,17'-(dichloropropylmethyl)-6,6',7,7'-6,6'-imino-7,7'
      binorphinan-3,4',14,14'-tetroldi-hydrochloride (norBNI). Study 3 was conducted to
      determine whether the sympatholytic effect of U-50488H could be prevented by
      norBNI. NorBNI blocked the sympatholytic effect of the U50488H for 90 mins. When
      norBNI was discontinued afterward and U-50488H was continued alone, a
      sympatholytic effect emerged within 30 mins. Collectively these observations
      support the hypothesis that the vagotonic influence of MEAP is not dependent on a
      sympatholytic influence. Furthermore, the sympatholytic effect is mediated
      independently by kappa-receptors. The sympatholytic effect of sustained kappa
      receptor stimulation appears to evolve gradually into a functional state not
      easily reversed.

PMID- 16565435
TI  - Nerve growth factor increases in pancreatic beta cells after streptozotocin
      induced damage in rats.
AB  - We investigated short-term in vivo and in vitro effects of streptozotocin (STZ)
      on pancreatic beta cells. Male Wistar rats were treated with 75 mg/kg STZ, and,
      after 4 hrs blood glucose and insulin were measured and islet cells were
      isolated, cultured for 16 hrs, and challenged with 5.6 and 15.6 mM glucose.
      Treated rats showed hyperglycemia (approximately 14 mM) and a 70% decrease in
      serum insulin levels as compared with controls. Although insulin secretion by
      isolated beta cells from STZ-treated rats was reduced by more than 80%, in both
      glucose concentrations, nerve growth factor (NGF) secretion by the same cells
      increased 10-fold. Moreover, NGF messenger RNA (mRNA) expression increased by 30%
      as compared with controls. Similar results were obtained in an in vitro model of
      islet cells, in which cells were exposed directly to STZ for 1, 2, and 4 hrs and
      then challenged for 3 hrs with the same glucose concentrations. Our data strongly
      suggest that an early increase in NGF production and secretion by beta cells
      could be an endogenous protective response to maintain cell survival and that
      diabetes mellitus may occur when this mechanism is surpassed.

PMID- 16565436
TI  - Involvement of protein kinases on the upregulation of endothelin receptors in rat
      basilar and mesenteric arteries.
AB  - Endothelin(B) (ET(B)) receptors are upregulated in experimental stroke or after
      24 hrs of organ culture. This upregulation is manifested both as stronger
      contraction and as an increase in ET(B) receptor messenger RNA (mRNA) levels. The
      present study was designed to evaluate the importance of protein kinases (c-Jun N
      terminal kinase [JNK], protein kinase C [PKC], and extracellular signal-regulated
      kinase [ERK1/2]) in ET(B) receptor upregulation after organ culture. Rat basilar
      and mesenteric arteries were incubated for 24 hrs in Dulbecco's modified Eagle's
      medium (DMEM) with or without the PKC inhibitor, RO-31-7549; the ERK1/2
      inhibitor, SB386023; or the JNK inhibitor, SP600125, added 3, 6, or 12 hrs after
      initiation of incubation. Subsequently, vessel segments were mounted in myographs
      and the contractile responses to ET-1 and sarafotoxin 6c were studied. The ET(B)
      and ET(A) receptor mRNA levels were determined with a real-time polymerase chain
      reaction (PCR). The cellular localization and protein level of ET(B) receptors
      were evaluated by immunohistochemistry. The PKC and ERK1/2 inhibitors attenuated
      the contraction induced by S6c in the basilar arteries more than in the
      mesenteric arteries. The efficiency of the inhibitors was proportional to the
      incubation time. Real-time PCR showed a decrease in the ET(B) receptor mRNA
      levels in arteries treated with PKC or ERK inhibitors. The JNK inhibitor had a
      significant inhibitory effect on ET(B) receptor upregulation in the basilar
      arteries. Immunohistochemistry revealed that the ET(B) receptor upregulation
      occured in the smooth-muscle cells and that it had the same pattern as in the
      quantitative PCR. Our results show that the PKC, ERK1/2, and JNK are more
      important for the upregulation of contractile ET(B) receptors in cerebral
      arteries compared with mesenteric arteries. ERK1/2 seems to be more important for
      the ET(B) receptor upregulation, as compared with PKC and JNK. The evaluation of
      the time dependency suggests that the phenomenon can be reversed even after its
      initiation.

PMID- 16565437
TI  - The saponin-mediated enhanced uptake of targeted saporin-based drugs is strongly
      dependent on the saponin structure.
AB  - Saponins are a group of plant glycosides consisting of a steroid or triterpenoid
      aglycone to which one or more sugar chains are attached. They exhibit cell
      membrane-permeabilizing properties and, thus, have been investigated for their
      therapeutic potential. Recently, at a non-permeabilizing concentration saponinum
      album from Gypsophila paniculata L. has been described to enhance the
      cytotoxicity of a chimeric toxin in a cell culture model. To elucidate whether
      this enhancing effect is also mediated by other saponins, we analyzed the ability
      of seven different saponins to enhance the cytotoxicity of a targeted chimeric
      toxin. The chimeric toxin is composed of saporin, a plant ribosome-inactivating
      toxin, a cleavable adapter, and human epidermal growth factor (EGF). Cytotoxicity
      on EGF receptor (EGFR)-bearing cells was analyzed both alone and after combined
      application of saponin and chimeric toxin. Only two of the tested saponins,
      quillajasaponin and saponinum album, enhanced cytotoxicity by more than 1,000
      fold, whereas the enhancement factors of the other saponins were only
      approximately 10-fold. In contrast to saponinum album, quillajasaponin enhanced
      the cytotoxicity both on control cells lacking EGFR and on target cells,
      indicating that, in this case, the enhancement is not target cell receptor
      specific. This is also the case for some of the saponins with low enhancement
      factors. Saponinum album resulted in a more than 13,600-fold receptor-specific
      enhancement, decreasing the 50% inhibitory concentration (IC(50)) from 2.4 nM to
      0.18 pM, which renders it the best option to promote saporin-3-based drug uptake
      while retaining specificity for the EGFR.

PMID- 16565438
TI  - Allyl isothiocyanate and its N-acetylcysteine conjugate suppress metastasis via
      inhibition of invasion, migration, and matrix metalloproteinase-2/-9 activities
      in SK-Hep 1 human hepatoma cells.
AB  - Cruciferous vegetables contain a series of relatively unique secondary
      metabolites of amino acids, called glucosinolates. Sinigrin, the predominant
      aliphatic glucosinolate in cruciferous vegetables, is hydrolyzed to yield allyl
      isothiocyanate (AITC), which, after absorption and metabolism in humans, is
      excreted in the urine as an N-acetylcysteine (NAC) conjugate. We have determined
      the inhibitory effects of AITC and its NAC conjugate on cell proliferation, the
      expression of matrix metalloproteinases (MMPs), adhesion, invasion, and migration
      in SK-Hep 1 human hepatoma cells. Our results demonstrate that AITC and NAC-AITC
      suppress SK-Hep 1 cell proliferation in a dose-dependent manner; by 25% and 30%
      for 10 microM AITC and 10 microM NAC-AITC, respectively. We examined the
      influence of AITC and NAC-AITC on the gene expression of MMPs and tissue
      inhibitors of metalloproteinase (TIMPs). Gelatin zymography also revealed a
      significant downregulation of MMP-2/-9 expression in SK-Hep1 cells treated with
      0.1-5 microM AITC and NAC-AITC compared with controls. Reverse transcriptase
      polymerase chain reaction revealed dose-dependent decreases in MMP-2/-9 messenger
      RNA levels in both AITC-treated and NAC-AITC-treated cells. TIMP-1/-2 activities
      were unaffected by treatment with AITC or NAC-AITC in our experiments. NAC-AITC
      inhibited cancer cell adhesion and invasion much more potently than its parent
      compound. NAC-AITC at 5 microM caused excellent inhibition of cell migration for
      48 hrs. These results demonstrate the potential of AITC and NAC-AITC as
      chemopreventive agents.

PMID- 16565440
TI  - Effects of Scutellaria baicalensis Georgi on macrophage-hepatocyte interaction
      through cytokines related to growth control of murine hepatocytes.
AB  - The aim of this study is to elucidate the effects of Scutellaria baicalensis
      Georgi (SbG) extract and its constituents on macrophage-hepatocyte interaction in
      primary cultures. By using trans-well primary Kupffer cell culture or conditioned
      medium (CM) from murine macrophage RAW264.7 cell line (RAW cells), effects of SbG
      on hepatocyte growth were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide and trypan blue exclusion assay. Cytokine production,
      antibody-neutralization studies, and molecular mechanisms of transforming growth
      factor (TGF)-beta1 gene expression were elucidated on SbG-treated RAW264.7 cells.
      In addition, recombinant human TGF-beta1 (r-human TGF-beta1) was added to
      elucidate the mechanisms of SbG effects on cultured hepatocytes.
      Immunohistochemistry using anti-NF-kappaB antibody was used to determine the
      possible signal transduction pathways in primary hepatocyte culture. The results
      showed that SbG stimulated the proliferation of cultured hepatocytes, possibly
      through NF-kappaB, but not of Toll-like receptor 4 activation; whereas SbG-RAW-CM
      and SbG in trans-well significantly suppressed the proliferation of hepatocytes.
      Antibody-neutralization studies revealed that TGF-beta1 was the main antimitotic
      cytokine in SbG-treated RAW cells CM. The growth stimulation effect of SbG on
      cultured hepatocytes was inhibited by exogenous administration of r-human TGF
      beta1. Furthermore, SbG induced NF-kB translocation into the nuclei of cultured
      cells. In the RAW264.7 line, SbG and baicalin stimulated TGF-beta1 gene
      expression via NF-kappaB and protein kinase C activation. We conclude that SbG
      stimulates hepatocyte growth via activation of the NF-kappaB pathway and induces
      TGF-beta1 gene expression through the Kupffer cell-hepatocyte interaction, which
      subsequently results in the inhibition of SbG-stimulated hepatocyte growth.

PMID- 16565439
TI  - Cross-linking cell surface chemokine receptors leads to isolation, activation,
      and differentiation of monocytes into potent dendritic cells.
AB  - Monocytes express on the cell surface several kinds of chemokine receptors that
      facilitate chemotaxis followed by differentiation in target tissues. In the
      present study, we found that a large number of monocytes from peripheral blood
      mononuclear cells (PBMCs) tightly adhered to plastic cell culture plates
      precoated with a monoclonal antibody (mAb, clone T312) specific for human CCR5
      but not an isotype control after overnight incubation. Soluble T312 did not
      induce such adhesion, indicating that cross-linking of CCR5 is required for the
      enhanced adhesion of monocytes. The adhesion was blocked by a PI3-K inhibitor and
      an anti-CD18 blocking mAb. Following the cross-linking of CCR5, monocytes
      synthesized high levels of M-CSF, RANTES, MIP-1 alpha, and MIP-1 beta associated
      with a readily detectable down modulation of CD14, CD4, CCR5, and CXCR4
      expression. The T312-enriched monocytes differentiated into dendritic cells (DCs)
      in the presence of interleukin-4 alone. After maturation with beta-interferon,
      the T312-induced DCs stimulated proliferation of allogeneic naive CD4(+) T cells
      accompanied by the synthesis of high levels of gamma-interferon in vitro.
      Furthermore, the T312-induced DCs were capable of stimulating antigen-specific
      human T- and B-cell immune responses in our hu-PBL-SCID mouse system. Finally,
      screening of other anti-chemokine receptor mAbs showed that select clones of mAbs
      against CXCR4 and CCR3 were also capable of facilitating enrichment of monocytes
      similar to T312. These results show that cross-linking of chemokine receptors on
      monocytes by appropriate mAbs leads to activation and differentiation of
      monocytes and that the method described herein provides an alternate simple
      strategy for adherence-based isolation of monocytes and generation of functional
      DCs.

PMID- 16565441
TI  - Fructose-fed rat hearts are protected against ischemia-reperfusion injury.
AB  - High fructose-fed (HFF) rat model is known to develop the insulin-resistant
      syndrome with a very similar metabolic profile to the human X syndrome. Such
      metabolic modifications have been associated with a high incidence of
      cardiovascular disease. The role of free radical attack in diabetes mellitus and
      its cardiovascular complications have been abundantly documented. The present
      study examined the susceptibility to myocardial ischemic injury and the
      involvement of free radical attack and/or protection in the metabolic disorders
      of high FF rats. Rats were divided into two experimental groups that received
      diet for 4 weeks: a control group (C, n=28) receiving a standard diet and a HFF
      group (FF, n=28), in which 58% of the total carbohydrate was fructose. The
      euglycemic clamp technique was performed to assess insulin resistance. For the
      ischemia-reperfusion procedure, rat hearts were isolated and perfused at constant
      pressure before they were subjected to a 30-min occlusion of the left coronary
      artery followed by 120 mins of reperfusion. Hemodynamic parameters were measured
      throughout the protocol. Infarct-to-risk ratio (I/R) was assessed at the end of
      the protocol by 2,3,4-triphenyltetrazolium chloride staining and planimetric
      analysis. Lipid peroxidation, antioxidant enzyme activity, level of vitamin E,
      and trace element status were measured in blood samples from both groups. Rats of
      the FF group developed an insulin resistance indicated by the glucose infusion
      rate, which was decreased by 47%. Infarct size was significantly reduced in rats
      from the FF group (19.9% +/- 6.6%) compared to rats from the control group (34.6%
      +/- 4.9%), and cardiac functional recovery at reperfusion was improved in the FF
      group. Lipid peroxidation and oxidative stress were higher in the FF group, as
      indicated by higher malonedialdehyde level, whereas plasma vitamin
      E/triacylglycerol ratio was also enhanced in this group. This study indicates
      that fructose feeding affords protection against in vitro ischemia-reperfusion
      injury, potentially implicating vitamin E.

PMID- 16565442
TI  - In vivo hyperoxic preconditioning prevents myocardial infarction by expressing
      bcl-2.
AB  - Preconditioning with oxidative stress has been demonstrated in vitro to stimulate
      the cellular adaptation to subsequent severe oxidative stress. However, it is
      uncertain whether this preconditioning works in vivo. In the present study, we
      examined in vivo the beneficial effect of oxidative preconditioning. After rats
      were pretreated with whole-body hyperoxygenation (100% O(2) at 3 atmosphere for
      20 mins, four cycles with 20-min intermission), isolated hearts were subjected to
      45-min ischemia followed by 90-min reperfusion. This hyperoxic preconditioning
      significantly reduced infarct size, cytochrome-c release, DNA fragmentation, and
      terminal deoxynucleotidyl transferase-mediated dUTD nick-end labeling-positive
      cell frequency in the left ventricle, biphasically with an early (30-min) and a
      delayed (48-hr) effect after the hyperoxygenation. Mechanistically, the NF-kappaB
      activity and Bcl-2 expression were enhanced in the hearts, and a NF-kappaB
      inhibitor, pyrrolidine dithiocarbamate, abolished the Bcl-2 induction as well as
      the infarct-limiting effect. An antioxidant, N-acetylcysteine, and protein kinase
      C (PKC) inhibitors chelerythrine and Go 6983 also blocked the preconditioning
      effects. These results indicate that hyperoxia induces myocardial tolerance
      against ischemia-reperfusion injury in association with Bcl-2 induction by NF
      kappaB activation through reactive oxygen species and PKC-dependent signaling
      pathway.

PMID- 16565443
TI  - Antioxidant and lysosomotropic properties of acute D-propranolol underlies its
      cardioprotection of postischemic hearts from moderate iron-overloaded rats.
AB  - The benefits of acute D-propranolol (D-Pro, non-beta-adrenergic receptor blocker)
      pretreatment against enhanced ischemia/reperfusion (I/R) injury of hearts from
      moderate iron-overloaded rats were examined. Perfused hearts from iron-dextran
      treated rats (450 mg/kg/week for 3 weeks, intraperitoneal administration)
      exhibited normal control function, despite iron treatment that elevated plasma
      iron and conjugated diene levels by 8.1-and 2.5-fold, respectively. However,
      these hearts were more susceptible to 25 mins of global I/R stress compared with
      non-loaded hearts; the coronary flow rate, aortic output, cardiac work, left
      ventricular systolic pressure, positive differential left ventricular pressure
      (dP/dt), and left ventricular developed pressure displayed 38%, 60%, 55%, 13%,
      41%, and 15% lower recoveries, respectively, and a 6.5-fold increase in left
      ventricular end-diastolic pressure. Postischemic hearts from iron-loaded rats
      also exhibited 5.6-, 3.48-, 2.43-, and 3.45-fold increases in total effluent iron
      content, conjugated diene levels, lactate dehydrogenase (LDH) activity, and
      lysosomal N-acetyl-beta-glucosaminidase (NAGA) activity, respectively, compared
      with similarly stressed non-loaded hearts. A comparison of detection time
      profiles during reperfusion suggests that most of the oxidative injury
      (conjugated diene) in hearts from iron-loaded rats occurred at later times of
      reperfusion (8.5-15 mins), and this corresponded with heightened tissue iron and
      NAGA release. D-Pro (2 microM infused for 30 mins) pretreatment before ischemia
      protected all parameters compared with the untreated iron-loaded group; pressure
      indices improved 1.2- to 1.6-fold, flow parameters improved 1.70- to 2.96-fold,
      cardiac work improved 2.87-fold, and end-diastolic pressure was reduced 56%. D
      Pro lowered total release of tissue iron, conjugated diene content, LDH activity,
      and NAGA activity 4.59-, 2.55-, 3.04-, and 4.14-fold, respectively, in the
      effluent of I/R hearts from the iron-loaded group. These findings suggest that
      the enhanced postischemic dysfunction and tissue injury of hearts from iron
      loaded rats was caused by excessive iron-catalyzed free radical stress, and that
      the membrane antioxidant properties of D-Pro and its stabilization of sequestered
      lysosomal iron by D-Pro may contribute to the cardioprotective actions of D-Pro.

PMID- 16565444
TI  - German tobacco industry's successful efforts to maintain scientific and political
      respectability to prevent regulation of secondhand smoke.
AB  - OBJECTIVE: To examine the tactics the tobacco industry in Germany used to avoid
      regulation of secondhand smoke exposure and to maintain the acceptance of public
      smoking. METHODS: Systematic search of tobacco industry documents available on
      the internet between June 2003 and August 2004. RESULTS: In West Germany,
      policymakers were, as early as the mid 1970s, well aware of the fact that
      secondhand smoke endangers non-smokers. One might have assumed that Germany, an
      international leader in environmental protection, would have led in protecting
      her citizens against secondhand smoke pollution. The tobacco manufacturers in
      Germany, however, represented by the national manufacturing organisation
      "Verband" (Verband der Cigarettenindustrie), contained and neutralised the early
      debate about the danger of secondhand smoke. This success was achieved by
      carefully planned collaboration with selected scientists, health professionals
      and policymakers, along with a sophisticated public relations programme.
      CONCLUSIONS: The strategies of the tobacco industry have been largely successful
      in inhibiting the regulation of secondhand smoke in Germany. Policymakers, health
      professionals, the media and the general public should be aware of this industry
      involvement and should take appropriate steps to close the gap between what is
      known and what is done about the health effects of secondhand smoke.

PMID- 16565445
TI  - Erectile dysfunction and smoking: subverting tobacco industry images of masculine
      potency.

PMID- 16565446
TI  - Happy Birthday Marlboro: the cigarette whose taste outlasts its customers.
AB  - Marlboro is 50 years old--and still killing its customers.

PMID- 16565448
TI  - Turkey: first tobacco litigation.

PMID- 16565447
TI  - USA: Pacific island clears the air.

PMID- 16565449
TI  - Spain: going smoke free.

PMID- 16565450
TI  - Lebanon: young stars turned to smoke.

PMID- 16565454
TI  - Challenges to the peer influence paradigm: results for 12-13 year olds from six
      European countries from the European Smoking Prevention Framework Approach study.
AB  - OBJECTIVE: To examine whether smoking onset in young adolescents is predicted by
      peer or parental smoking. DESIGN: Longitudinal design with one pretest and one
      follow-up at 12 months. SETTING: Schools in Finland, Denmark, the Netherlands,
      the United Kingdom, Spain and Portugal. PARTICIPANTS: 7102 randomly selected
      adolescents from six countries. Mean age was 12.78 years. MAIN OUTCOME MEASURES:
      Smoking behaviour of adolescents, peers and parents. RESULTS: No support was
      found for peer smoking as an important predictor of smoking onset in most
      countries. Support was found for the selection paradigm, implying that
      adolescents choose friends with similar smoking behaviour. Support for the impact
      of parents on adolescent behaviour and the choice of friends was also found.
      CONCLUSIONS: Smoking uptake in this age cohort may be more strongly influenced by
      personal and parental influences than initially believed. Hence, social
      inoculation programmes teaching youngsters to resist the pressures to smoke may
      be less appropriate if youngsters have a positive attitude towards smoking,
      associate smoking with various advantages and look for peers with similar values.
      For this group attitudes towards smoking may thus guide future friend selection.

PMID- 16565455
TI  - Litigation in Argentina: challenging the tobacco industry.
AB  - OBJECTIVE: To evaluate the processes and outcomes of tobacco litigation in
      Argentina and to analyse the strategies of the tobacco industry to oppose
      litigation using tobacco industry documents. METHODS: A systematic search of
      tobacco industry documents on the internet dating from 1978 to 2002. Law library
      searches using Argentinean official and unofficial reports systems were combined
      with computerised online searches. RESULTS: There have been at least 15 failed
      litigation cases in Argentina and the tobacco industry presented a concerted
      defence in every claim regardless of cost. We categorised 11 cases as product
      liability and nicotine addiction, two as health care reimbursement, and two as
      criminal law and secondhand smoke. Industry strategies included hiring legal
      consultants from prestigious international and Argentinean law firms and
      developing litigation prevention programmes. Industry monitored legal academic
      meetings, controlled the development of new product liability legislation,
      obtained favourable opinions from experts, and closely observed the development
      of litigation in Argentina. CONCLUSION: The strategies used by the industry have
      been successful in preventing recovery for tobacco injuries through litigation.
      Argentinean health advocates and lawyers need to be aware of the roles and
      strategies of the tobacco industry in order to develop effective litigation in
      Argentina.

PMID- 16565456
TI  - A group randomised trial of two methods for disseminating a smoking cessation
      programme to public antenatal clinics: effects on patient outcomes.
AB  - OBJECTIVE: To assess the differential effectiveness of two methods of
      disseminating a smoking cessation programme to public hospital antenatal clinics.
      DESIGN: Group randomised trial. SETTING: 22 antenatal clinics in New South Wales,
      Australia. INTERVENTION: Clinics were allocated to a simple dissemination (SD)
      condition (11 clinics) which received a mail-out of programme resources or to an
      intensive dissemination (ID) condition (11 clinics) which included the mail-out
      plus feedback, training, and ongoing support with midwife facilitator. MAIN
      OUTCOME MEASURES: Independent cross sectional surveys of women on a second or
      subsequent visit undertaken pre-dissemination and 18 months after dissemination.
      Outcomes were: (1) levels of smoking status assessment by clinic staff; (2)
      proportion of women identifying as having been smokers at their first visit who
      reported receiving cessation advice; (3) proportion of these women who had quit
      (self report and expired air carbon monoxide (CO)); and (4) smoking prevalence
      among all women (self report and CO). SUBJECTS: 5849 women pre-dissemination
      (2374 SD, 3475 ID) and weighted sample of 5145 women post-dissemination (2302 SD,
      2843 ID). RESULTS: There were no significant differences between the groups on
      change on any outcome. Change in either group was minimal. In the post
      dissemination survey, the cessation proportions were 6.4% (SD) and 10.5% (ID).
      CONCLUSIONS: Relatively modest strategies for encouraging incorporation of
      smoking cessation activities into antenatal care were not effective in the long
      term. Alternative strategies should be implemented and evaluated. The findings
      reinforce the importance of a whole population approach to tobacco control.

PMID- 16565457
TI  - Youth smoking prevention and tobacco industry revenue.
AB  - OBJECTIVES: Epidemiological surveys make it clear that youth smoking contributes
      to both current and future tobacco industry revenue: over 80% of adult smokers
      reportedly began smoking before age 18. This paper estimates annual and lifetime
      revenue from youth smoking, and highlights the association between declines in
      youth smoking and declines in tobacco industry revenue. MAIN OUTCOME MEASURES:
      This paper reports the amount of tobacco industry revenue generated by youth
      smoking at two points in time (1997 and 2002), and describes the distribution of
      youth generated tobacco income among the major tobacco companies. The authors
      project the amount of tobacco industry revenue that will be generated by members
      of two cohorts (the high school senior classes of 1997 and 2002) over the course
      of their lifetimes. RESULTS: In 1997, youth consumed 890 million cigarette packs,
      generating $737 million in annual industry revenue. By 2002, consumption dropped
      to 541 million packs and revenue increased to nearly $1.2 billion. Fifty eight
      per cent of youth generated revenue goes to Philip Morris USA, 18% to Lorillard,
      and 12% to RJ Reynolds. The authors project that, over the course of their lives,
      the 1997 high school senior class will smoke 12.4 billion packs of cigarettes,
      generating $27.3 billion in revenue. The 2002 high school senior class is
      projected to smoke 10.4 billion packs, generating $22.9 billion in revenue over
      the course of their lives. CONCLUSIONS: Cigarette price increases from 1997 to
      2002 have resulted in greater revenue for the tobacco industry, despite declines
      in youth smoking prevalence. However, in the absence of further cigarette price
      increases, declines in youth smoking are projected to lead ultimately to a loss
      of approximately $4 billion in future tobacco industry revenue from a single high
      school cohort.

PMID- 16565458
TI  - Non-smokers seeking help for smokers: a preliminary study.
AB  - OBJECTIVES: To examine the phenomenon of non-smokers spontaneously taking action
      to seek help for smokers; to provide profiles of non-smoking helpers by language
      and ethnic groups. SETTING: A large, statewide tobacco quitline (California
      Smokers' Helpline) in operation since 1992 in California, providing free
      cessation services in English, Spanish, Mandarin, Cantonese, Korean, and
      Vietnamese. SUBJECTS: Callers between August 1992 and September 2005 who
      identified themselves as either white, black, Hispanic, American Indian, or Asian
      (n = 349,110). A subset of these were "proxies": callers seeking help for someone
      else. For more detailed analysis, n = 2143 non-smoking proxies calling from
      October 2004 through September 2005. MAIN OUTCOME MEASURES: Proportions of
      proxies among all callers in each of seven language/ethnic groups; demographics
      of proxies; and proxies' relationships to smokers on whose behalf they called.
      RESULTS: Over 22 000 non-smoking proxies called. Proportions differed
      dramatically across language/ethnic groups, from mean (+/-95% confidence
      interval) 2.7 (0.3)% among English-speaking American Indians through 9.3 (0.3)%
      among English-speaking Hispanics to 35.3 (0.7)% among Asian-speaking Asians.
      Beyond the differences in proportion, however, remarkable similarities emerged
      across all groups. Proxies were primarily women (79.2 (1.7)%), living in the same
      household as the smokers (65.0 (2.1)%), and having either explicit or implicit
      understandings with the smokers that calling on their behalf was acceptable (90.0
      (1.3)%). CONCLUSIONS: The willingness of non-smokers to seek help for smokers
      holds promise for tobacco cessation and may help address ethnic and language
      disparities. Non-smoking women in smokers' households may be the first group to
      target.

PMID- 16565459
TI  - Price and cigarette consumption in Europe.
AB  - OBJECTIVE: To analyse the variation in demand for tobacco according to price of
      cigarettes across the European region. DESIGN: Cross-sectional study. SETTING:
      All the 52 countries of the European region. PARTICIPANTS: For each European
      country, data were collected on annual per adult cigarette consumption (2000),
      smoking prevalence (most recent), retail price of a pack of local and foreign
      brand cigarettes (around 2000), the gross domestic product adjusted by purchasing
      power parities, and the adult population (2000). MAIN OUTCOME MEASURE: Price
      elasticity of demand for cigarettes (that is, the change in cigarette consumption
      according to a change in tobacco price) across all the European countries,
      estimated by double-log multiple linear regression. RESULTS: Controlling for male
      to female prevalence ratio, price elasticities for consumption were -0.46 (95%
      confidence interval (CI) -0.74 to -0.17) and -0.74 (95% CI -1.13 to -0.35) for
      local and foreign brand, respectively. The inverse relation between cigarette
      price and consumption was stronger in countries not in the European Union (price
      elasticity for foreign brand cigarettes of -0.8) as compared to European Union
      countries (price elasticity of -0.4). CONCLUSIONS: The result that, on average,
      in Europe smoking consumption decreases 5-7% for a 10% increase in the real price
      of cigarettes strongly supports an inverse association between price and
      cigarette smoking.

PMID- 16565460
TI  - Tobacco industry use of judicial seminars to influence rulings in products
      liability litigation.
AB  - OBJECTIVES: This paper examines the tobacco industry's efforts to influence
      litigation by sponsoring judicial seminars. METHODS: Thousands of internal
      tobacco documents were examined, including memos, reports, presentations, and
      newsletters. Connections to outside organisations were corroborated by examining
      tobacco industry financial records, budgets, and letters pledging funds. Facts
      about outside organisations were triangulated through examining their websites
      and publicly-filed financial records, and verifying facts through their
      representatives' statements in newspaper and law review articles. RESULTS: There
      are direct financial ties between the tobacco industry and groups that organise
      judicial seminars in an effort to influence jurisprudence, and judges who attend
      these seminars may be breaching judicial ethics either by not inquiring about the
      source of funding or by ignoring funding by potential litigants. CONCLUSIONS: The
      tobacco industry's attempts to clandestinely influence judges' decisions in cases
      to which they are a party endangers the integrity of the judiciary.

PMID- 16565461
TI  - Cost of tobacco-related diseases, including passive smoking, in Hong Kong.
AB  - BACKGROUND: Costs of tobacco-related disease can be useful evidence to support
      tobacco control. In Hong Kong we now have locally derived data on the risks of
      smoking, including passive smoking. AIM: To estimate the health-related costs of
      tobacco from both active and passive smoking. METHODS: Using local data, we
      estimated active and passive smoking-attributable mortality, hospital admissions,
      outpatient, emergency and general practitioner visits for adults and children,
      use of nursing homes and domestic help, time lost from work due to illness and
      premature mortality in the productive years. Morbidity risk data were used where
      possible but otherwise estimates based on mortality risks were used. Utilisation
      was valued at unit costs or from survey data. Work time lost was valued at the
      median wage and an additional costing included a value of USD 1.3 million for a
      life lost. RESULTS: In the Hong Kong population of 6.5 million in 1998, the
      annual value of direct medical costs, long term care and productivity loss was
      USD 532 million for active smoking and USD 156 million for passive smoking;
      passive smoking accounted for 23% of the total costs. Adding the value of
      attributable lives lost brought the annual cost to USD 9.4 billion. CONCLUSION:
      The health costs of tobacco use are high and represent a net loss to society.
      Passive smoking increases these costs by at least a quarter. This quantification
      of the costs of tobacco provides strong motivation for legislative action on
      smoke-free areas in the Asia Pacific Region and elsewhere.

PMID- 16565463
TI  - Smoking and erectile dysfunction: findings from a representative sample of
      Australian men.
AB  - OBJECTIVES: To examine whether there is an association between smoking and
      erectile dysfunction in a representative sample of Australian men. DESIGN:
      Secondary analysis of cross-sectional survey data from the Australian Study of
      Health and Relationships. PARTICIPANTS: 8367 Australian men aged 16-59 years.
      MAIN OUTCOME MEASURES: Erectile dysfunction was identified in men who reported
      having had trouble keeping an erection when they wanted to, a problem which
      persisted for at least one month over the previous year. Variables examined in
      multivariate logistic regression analyses included age, education, presence of
      cardiovascular disease and diabetes, and current alcohol and tobacco consumption.
      RESULTS: Almost one in 10 of the respondents (9.1%) reported erectile dysfunction
      that lasted for at least one month over the previous year. More than a quarter
      (27.2%) of respondents were current smokers, with 20.9% smoking < or = 20
      cigarettes per day, and 6.3% smoking > 20 cigarettes per day. Compared with non
      smokers, the adjusted odds ratios for erectile dysfunction were 1.24 (95%
      confidence interval (CI) 1.01 to 1.52, p = 0.04) for those smoking < or = 20
      cigarettes per day and 1.39 (95% CI 1.05 to 1.83, p = 0.02) for those smoking >
      20 cigarettes per day, after adjusting for other confounding factors. Older age,
      low level of education, and taking medications for cardiovascular disease were
      also independently and positively associated with erectile dysfunction. In
      contrast, moderate alcohol consumption (1-4 drinks per day) significantly reduced
      the likelihood of having erectile dysfunction. CONCLUSIONS: Erectile dysfunction
      is a significant health concern affecting around one in 10 Australian men aged 16
      59 years. Current smoking is significantly associated with erectile dysfunction
      in Australian males. This association was strengthened as the number of
      cigarettes smoked increased. Health promotion programmes could use the link
      between smoking and erectile dysfunction to help reduce smoking levels among men.

PMID- 16565462
TI  - Changes in smoking prevalence in Russia, 1996-2004.
AB  - OBJECTIVES: In Russia, smoking prevalence has historically been high in men and
      relatively low in women. Female smoking prevalence is predicted to rise but
      assessment of changes has been limited by the lack of comparable data. Changes in
      the prevalence of smoking in Russia between 1996 and 2004, and whether theses
      changes differed by sociodemographic groups, were investigated. DESIGN: Repeated
      national interview surveys in 1996 (731 men and 868 women) and 2004 (727 men and
      864 women) aged 18 years or more. MAIN OUTCOME MEASURE: Prevalence of current
      smoking. RESULTS: The age standardised prevalence of smoking in 1996 and 2004 was
      61% and 63%, respectively in men and 15% and 16%, respectively in women (both p
      values > 0.4). In men, the prevalence of smoking seemed to decline in those with
      university education (from 51% to 40%, p = 0.085). Among women, smoking appeared
      to increase in those with university education (from 10% to 17%, p = 0.071) and
      low levels of self-reported material deprivation (from 11% to 18%, p = 0.053).
      There was a pronounced increase in prevalence among women living in villages
      (from 8% to 14%, p = 0.049); the strong urban/rural gradient seen in 1996 became
      considerably weaker by 2004. CONCLUSIONS: Overall smoking prevalence in both men
      and women in Russia remained stable between 1996 and 2004 but, given the sample
      size, a moderate increase in female smoking cannot be ruled out. In men, smoking
      increased among the least educated and declined in the most educated. In women
      the opposite appeared to occur, in addition to an increase in smoking in rural
      areas. More long term monitoring of smoking patterns in Russia, especially among
      women, using sufficiently large surveys, is required.

PMID- 16565465
TI  - Can carbon monoxide analysers be fuelled by alcohol intake?

PMID- 16565464
TI  - Point of purchase cigarette promotions before and after the Master Settlement
      Agreement: exploring retail scanner data.
AB  - BACKGROUND: Evidence indicates that point of purchase (POP) advertising and
      promotions for cigarettes have increased since the Master Settlement Agreement
      (MSA). Retail promotions have the potential to offset the effects of cigarette
      tax and price increases and tobacco control programmes. OBJECTIVE: To describe
      the trend in the proportion of cigarette sales that occur as part of a POP
      promotion before and after the MSA. DESIGN: Scanner data were analysed on
      cigarette sales from a national sample of grocery stores, reported quarterly from
      1994 through 2003. The proportion of total cigarette sales that occurred under
      any of three different types of POP promotions is presented. RESULTS: The
      proportion of cigarettes sold under a POP promotion increased notably over the
      sample period. Large increases in promoted sales are observed following
      implementation of the MSA and during periods of sustained cigarette excise tax
      increases. CONCLUSIONS: The observed pattern of promoted cigarette sales is
      suggestive of a positive relationship between retail cigarette promotions, the
      MSA, and state cigarette tax increases. More research is needed to describe fully
      the relationship between cigarette promotions and tobacco control policy.

PMID- 16565466
TI  - Preliminary effects of Italy's ban on smoking in enclosed public places.

PMID- 16565467
TI  - The pharmacology of mithridatum: a 2000-year-old remedy.

PMID- 16565468
TI  - Targeting PGE2 receptor subtypes rather than cyclooxygenases: a bridge over
      troubled water?
AB  - Prostaglandins (PG) are synthesized by the sequential action of phosholipases,
      cyclooxygenases (COX)-1 and COX-2, and specific terminal synthases, and exert
      their diverse biological effects through several membrane receptors. In
      particular, PGE2 is involved in many normal and pathological pathways that are
      mediated by four different E prostanoid receptors (EP1-4). Selective COX-2
      inhibitors (Coxibs) have analgesic and antipyretic effects that are
      indistinguishable from those of nonsteroidal anti-inflammatory drugs (NSAIDs),
      but some possess hazardous cardiovascular side effects. Recent results indicate
      that EP1 and EP4 antagonists might prove useful for inhibiting the unwanted
      actions of COX-2. Has the time come for research to examine earnestly the
      selective antagonism of EP subtypes rather than further the development of direct
      COX-2 inhibitors?

PMID- 16565469
TI  - sorLA: sorting out APP.
AB  - The accumulation of amyloid-beta peptides in the brain is a major factor of
      Alzheimer Disease. Central to the production of the amyloid-beta peptides are the
      proteolytic secretases, which, recently, have been important targets of drug
      discovery. Newly published results indicate that the sorting protein-related
      receptor sorLA/LR11 regulates processing and trafficking of the precursor of the
      amyloid-beta peptides, revealing an alternative target for developing molecular
      clinical therapeutic compounds for Alzheimer Disease.

PMID- 16565470
TI  - Histamine H3 receptor antagonists: preclinical promise for treating obesity and
      cognitive disorders.
AB  - The histamine H3 receptor is an attractive G protein-coupled receptor drug target
      that regulates neurotransmission in the central nervous system and plays a role
      in cognitive and homeostatic functions. Drug discovery efforts by numerous
      pharmaceutical companies have focused on the preclinical development of H3
      receptor antagonists for the potential treatment of attention-deficit
      hyperactivity disorder, dementias, schizophrenia, as well as obesity and sleep
      disorders. This receptor exhibits molecular, pharmacological, and functional
      heterogeneity that informs the preclinical development of effective antagonists.
      Herein, we describe the biological and chemical implications for developing H3
      receptor antagonists and their therapeutic potential as disclosed through animal
      models of cognition, sleep, and obesity.

PMID- 16565471
TI  - Iron dysregulation and neurodegeneration: the molecular connection.
AB  - Iron is essential for many biological processes however excess concentrations can
      be harmful to many tissues. Its amounts must therefore be carefully regulated in
      all cells of the body including those in the brain. Increased amounts of iron
      have been reported in many neurodegenerative disorders. Whether this increased
      iron contributes to neurodegeneration has been considered controversial. In this
      review, we discuss some recently identified anomalies in proteins linked with
      iron metabolism which signify a critical role for iron dysregulation in
      neurodegeneration.

PMID- 16565472
TI  - Advanced drug delivery systems that target the vascular endothelium.
AB  - Targeted drug delivery to endothelial cells lining the vascular lumen will
      provide effective, precise and safe therapeutic interventions for treatment of
      diverse disease conditions. Rational design of such drug delivery systems (DDS)
      includes the following intertwined tasks: 1) selection of proper target
      determinants on endothelial surfaces, such as cell adhesion molecules,
      ectopeptidases, or caveolar antigens; 2) production of affinity ligands useful
      for targeting, such as affinity peptides, antibodies, or their fragments; 3)
      selection and adopting of suitable delivery vehicles (such as liposomes or
      polymer nanocarriers); and 4) formulation of DDS with optimal targeting and
      therapeutic features. Important therapeutic features of DDS include: 1)
      sufficient targeting effectiveness, circulation time, and safety (i.e., lack of
      systemic and local adverse effects); 2) precise subcellular localization of drugs
      targeted to endothelial cells; and 3) adequate amplitude, kinetics, and duration
      of effects. This review utilizes examples of DDS-mediated interventions in
      vascular inflammation, oxidative stress, and thrombosis and analyzes them in an
      attempt to create design parameters that best regulate the pharmacological and
      therapeutic features of DDS that target endothelial cells.

PMID- 16565473
TI  - Biological and geological times.

PMID- 16565474
TI  - Monitoring of cAMP synthesis and degradation in living cells.
AB  - cAMP is an important second messenger with a plethora of cellular effects and
      biological roles. To monitor and visualize cAMP in intact living cells,
      electrophysiological and fluorescent methods have been developed based on
      activation of all three types of cAMP effectors: protein kinase A, cyclic
      nucleotide-gated channels, and exchange protein directly activated by cAMP. In
      this review, we describe and compare these techniques in terms of their
      robustness, sensitivity and spatio-temporal resolution.

PMID- 16565475
TI  - From bacteria to man: archaic proton-dependent peptide transporters at work.
AB  - Uptake of nutrients into cells is essential to life and occurs in all organisms
      at the expense of energy. Whereas in most prokaryotic and simple eukaryotic cells
      electrochemical transmembrane proton gradients provide the central driving force
      for nutrient uptake, in higher eukaryotes it is more frequently coupled to sodium
      movement along the transmembrane sodium gradient, occurs via uniport mechanisms
      driven by the substrate gradient only, or is linked to the countertransport of a
      similar organic solute. With the cloning of a large number of mammalian nutrient
      transport proteins, it became obvious that a few "archaic'' transporters that
      utilize a transmembrane proton gradient for nutrient transport into cells can
      still be found in mammals. The present review focuses on the electrogenic peptide
      transporters as the best studied examples of proton-dependent nutrient
      transporters in mammals and summarizes the most recent findings on their
      physiological importance. Taking peptide transport as a general phenomenon found
      in nature, we also include peptide transport mechanisms in bacteria, yeast,
      invertebrates, and lower vertebrates, which are not that often addressed in
      physiology journals.

PMID- 16565476
TI  - Cell-cell communication beyond connexins: the pannexin channels.
AB  - Direct cell-to-cell communication through specialized intercellular channels is a
      characteristic feature of virtually all multi-cellular organisms. The remarkable
      functional conservation of cell-to-cell coupling throughout the animal kingdom,
      however, is not matched at the molecular level of the structural protein
      components. Thus protostomes (including nematodes and flies) and deuterostomes
      (including all vertebrates) utilize two unrelated families of gap-junction genes,
      innexins and connexins, respectively. The recent discovery that pannexins, a
      novel group of proteins expressed by several organisms, are able to form
      intercellular channels has started a quest to understand their evolutionary
      relationship and functional contribution to cell communication in vivo. There are
      three pannexin genes in mammals, two of which are co-expressed in the developing
      and adult brain. Of note, pannexin1 can also form Ca2+-activated hemichannels
      that open at physiological extracellular Ca2+ concentrations and exhibit distinct
      pharmacological properties.

PMID- 16565477
TI  - The ins and outs of iron homeostasis.
AB  - Iron is an essential element that is toxic when it accumulates in excess.
      Intricate regulatory mechanisms have evolved to maintain iron homeostasis within
      cells and between different tissues of complex organisms. This review discusses
      the proteins involved in iron transport and storage and their regulation in
      health and disease.

PMID- 16565478
TI  - Dense-core secretory granule biogenesis.
AB  - The dense-core secretory granule is a key organelle for secretion of hormones and
      neuropeptides in endocrine cells and neurons, in response to stimulation.
      Cholesterol and granins are critical for the assembly of these organelles at the
      trans-Golgi network, and their biogenesis is regulated quantitatively by
      posttranscriptional and posttranslational mechanisms.

PMID- 16565479
TI  - Role of the adventitia in pulmonary vascular remodeling.
AB  - An increasing volume of experimental data indicates that the adventitial
      fibroblast, in both the pulmonary and systemic circulations, is a critical
      regulator of vascular wall function in health and disease. A rapidly emerging
      concept is that the vascular adventitia acts as biological processing center for
      the retrieval, integration, storage, and release of key regulators of vessel wall
      function. In response to stress or injury, resident adventitial cells can be
      activated and reprogrammed to exhibit different functional and structural
      behaviors. In fact, under certain conditions, the adventitial compartment may be
      considered the principal injury-sensing tissue of the vessel wall. In response to
      vascular stresses such as overdistension and hypoxia, the adventitial fibroblast
      is activated and undergoes phenotypic changes, which include proliferation,
      differentiation, upregulation of contractile and extracellular matrix proteins,
      and release of factors that directly affect medial smooth muscle cell tone and
      growth and that stimulate recruitment of inflammatory and progenitor cells to the
      vessel wall. Each of these changes in fibroblast phenotype modulates either
      directly or indirectly changes in overall vascular function and structure. The
      purpose of this review is to present the current evidence demonstrating that the
      adventitial fibroblast acts as a key regulator of pulmonary vascular function and
      structure from the "outside-in."

PMID- 16565480
TI  - Vasopressin and pair-bond formation: genes to brain to behavior.
AB  - Microtine rodents provide an excellent model for the study of the neurobiology of
      social bonds. In this review, we discuss how the presence of a microsatellite
      sequence in the prairie vole vasopressin receptor gene may determine vasopressin
      receptor binding patterns in the brain and how these patterns may in turn affect
      social behavior.

PMID- 16565481
TI  - Systemic viral infections and collateral damage in the liver.

PMID- 16565482
TI  - Commonality of defensive roles of COX-2 in the lung and gut.

PMID- 16565484
TI  - Permselective dysfunction of podocyte-podocyte contact upon angiotensin II
      unravels the molecular target for renoprotective intervention.
AB  - Ameliorating the function of the glomerular barrier to circulating proteins by
      blocking angiotensin II (Ang II) translates into less risk of progression toward
      end-stage renal failure in diabetic and nondiabetic nephropathies. However, the
      mechanisms underlying this barrier protection are not clear. Specialized contacts
      between adjacent podocytes are major candidate targets, and the actin
      cytoskeleton is emerging as a regulatory element. Here, we present data
      demonstrating that Ang II induced reorganization of F-actin fibers and
      redistribution of zonula occludens-1 (ZO-1) that is physically associated with
      actin in murine podocytes. These effects were paralleled by increased albumin
      permeability across podocyte monolayers. The F-actin stabilizer jasplakinolide
      prevented both ZO-1 redistribution and albumin leakage, suggesting that actin
      cytoskeleton rearrangement is instrumental to podocyte permselective dysfunction
      induced by Ang II. Changes in both F-actin and ZO-1 patterns were confirmed in
      glomeruli of rat isolated perfused kidneys on short infusion of Ang II, leading
      to increased protein excretion. Podocyte dysfunction was mediated by Ang II type
      1 receptor and was partly dependent on Src kinase-phospholipase C activation.
      These data demonstrate that strategies aimed at stabilizing podocyte-podocyte
      contacts and targeting the relevant intracellular signal transduction are crucial
      to renoprotection.

PMID- 16565485
TI  - Thrombin-activatable fibrinolysis inhibitor deficiency attenuates bleomycin
      induced lung fibrosis.
AB  - Decreased fibrinolytic function favors the development of pulmonary fibrosis.
      Thrombin-activatable fibrinolysis inhibitor (TAFI) is a strong suppressor of
      fibrinolysis, but its role in lung fibrosis is unknown. Therefore, we compared
      bleomycin-induced lung fibrosis in TAFI-deficient, heterozygous, and wild-type
      mice. The animals were sacrificed 21 days after bleomycin administration, and
      markers of lung fibrosis and inflammation were measured. The bronchoalveolar
      lavage fluid levels of total protein, neutrophil proteases (elastase,
      myeloperoxidase), cytokines (tumor necrosis factor-alpha, interleukin-13),
      chemokine (monocyte chemoattractant protein-1), coagulation activation marker
      (thrombin-antithrombin complex), total soluble collagen, and growth factors
      (platelet-derived growth factor, transforming growth factor-beta1, granulocytic
      macrophage growth factor) were significantly decreased in knockout mice compared
      to wild-type mice. Further, histological findings of fibrosis, fibrin deposition,
      and hydroxyproline and collagen content in the lung were significantly decreased
      in knockout mice compared to wild-type mice. Depletion of fibrinogen by ancrod
      treatment led to equalization in the amount of fibrosis and collagen deposition
      in the lungs of knockout and wild-type mice. No difference was detected in body
      temperature or arterial pressure between the different mouse phenotypes. These
      results suggest that the anti-fibrinolytic activity of TAFI promotes lung
      fibrosis by hindering the rate at which fibrin is degraded.

PMID- 16565483
TI  - Lipoxin A(4) regulates bronchial epithelial cell responses to acid injury.
AB  - Aspiration of gastric acid commonly injures airway epithelium and, if severe, can
      lead to respiratory failure from acute respiratory distress syndrome. Recently,
      we identified cyclooxygenase-2 (COX-2)-derived prostaglandin E(2) (PGE(2)) and
      lipoxin A(4) (LXA(4)) as pivotal mediators in vivo for resolution of acid
      initiated acute lung injury. To examine protective mechanisms for these mediators
      in the airway, we developed an in vitro model of acid injury by transiently
      exposing well-differentiated normal human bronchial epithelial cells to
      hydrochloric acid. Transmission electron microscopy revealed selective injury to
      superficial epithelial cells with disruption of cell attachments and cell
      shedding. The morphological features of injury were substantially resolved within
      6 hours. Acid triggered and early marked increases in COX-2 expression and PGE(2)
      production, and acid-induced PGE(2) significantly increased epithelial LXA(4)
      receptor (ALX) expression. LXA(4) is generated in vivo during acute lung injury,
      and we observed that nanomolar quantities increased basal epithelial cell
      proliferation and potently blocked acid-triggered interleukin-6 release and
      neutrophil transmigration across well-differentiated normal human bronchial
      epithelial cells. Expression of recombinant human ALX in A549 airway epithelial
      cells uncovered ALX-dependent inhibition of cytokine release by LXA(4). Together,
      these findings indicate that injured bronchial epithelial cells up-regulate ALX
      in a COX-2-dependent manner to promote LXA(4)-mediated resolution of airway
      inflammation.

PMID- 16565486
TI  - Maintenance of Bad phosphorylation prevents apoptosis of rat hepatic sinusoidal
      endothelial cells in vitro and in vivo.
AB  - To elucidate the mechanism of apoptosis of liver sinusoidal endothelial cells
      (SECs), we examined the phosphorylation status of Bad and its upstream signaling
      molecules during apoptosis in culture and after ischemia-reperfusion injury. Rat
      SECs were isolated by the immunomagnetic method, and 2 days after culture, most
      SECs underwent apoptosis, which was associated with decreased tyrosine
      phosphorylation of cellular proteins. Addition of orthovanadate (OV), a protein
      tyrosine phosphatase inhibitor, sustained cellular protein phosphorylation and
      strongly inhibited apoptosis. Bad was dephosphorylated at Ser-112 and Ser-136
      during apoptosis, but the phosphorylation status of Bad was maintained in the
      presence of OV. OV activated the Akt, extracellular signal-regulated protein
      kinase, and p38 mitogen-activated protein kinase pathways, which are involved in
      Bad phosphorylation. In the absence of OV, depletion of Bad by RNA interference
      conferred resistance to apoptosis. Hepatic injury after ischemia-reperfusion was
      alleviated by OV treatment, with significant inhibition of SEC apoptosis. SEC
      apoptosis in vivo was associated with dephosphorylation of Bad, Akt, and
      extracellular signal-regulated protein kinase, which was blocked by OV treatment.
      Our data suggest that maintenance of Bad phosphorylation is important in the
      prevention of SEC apoptosis and that the anti-apoptotic property of OV might have
      therapeutic utility.

PMID- 16565487
TI  - Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated
      with apoptosis sensitivity induced by cholesterol-depleting agents.
AB  - Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate
      various cellular functions, including cell survival. To better understand the
      role of rafts in tumor progression and therapeutics, we investigated the effect
      of raft disruption on cell viability and compared raft levels in human cancer
      cell lines versus their normal counterparts. Here, we report that cholesterol
      depletion using methyl-beta cyclodextrin caused anoikis-like apoptosis, which in
      A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3
      activation, and Akt inactivation regardless of epidermal growth factor receptor
      activation. Cholesterol repletion replenished rafts on the cell surface and
      restored Akt activation and cell viability. Moreover, the breast cancer and the
      prostate cancer cell lines contained more lipid rafts and were more sensitive to
      cholesterol depletion-induced cell death than their normal counterparts. These
      results indicate that cancer cells contain increased levels of rafts and suggest
      a potential use of raft-modulating agents as anti-cancer drugs.

PMID- 16565488
TI  - The critical roles of serum/glucocorticoid-regulated kinase 3 (SGK3) in the hair
      follicle morphogenesis and homeostasis: the allelic difference provides novel
      insights into hair follicle biology.
AB  - Mutation in the serum/glucocorticoid regulated kinase 3 (Sgk3, also known as Sgkl
      or Cisk) gene causes both defective hair follicle development and altered hair
      cycle in mice. We examined Sgk3-mutant YPC mice (YPC-Sgk3(ypc)/Sgk3(ypc)) and
      found expression of SGK3 protein with altered function. In the hair follicles of
      YPC mice, the aberrant differentiation and poor proliferation of hair matrix
      keratinocytes during the period of postnatal hair follicle development resulted
      in a complete lack of hair medulla and weak hair. Surprisingly, the length of
      postnatal hair follicle development and anagen term was shown to be dramatically
      shortened. Also, phosphorylation of GSK3beta at Ser9 and the nuclear accumulation
      of beta-catenin were reduced in the developing YPC hair follicle, suggesting that
      phosphorylation of GSK3beta and WNT-beta-catenin pathway takes part in the SGK3
      dependent regulation of hair follicle development. Moreover, the above-mentioned
      features, especially the hair-cycling pattern, differ from those in other Sgk3
      null mutant strains, suggesting that the various patterns of dysfunction in the
      SGK3 protein may result in phenotypic variation. Our results indicate that SGK3
      is a very important and characteristic molecule that plays a critical role in
      both hair follicle morphogenesis and hair cycling.

PMID- 16565489
TI  - Activation of the canonical wingless/T-cell factor signaling pathway promotes
      invasive differentiation of human trophoblast.
AB  - The molecular mechanisms governing invasive differentiation of human trophoblasts
      remain largely elusive. Here, we investigated the role of Wnt-beta-catenin-T-cell
      factor (TCF) signaling in this process. Reverse transcriptase-polymerase chain
      reaction and Western blot analyses demonstrated expression of Wnt ligands,
      frizzled receptors, LRP-6, and TCF-3/4 transcription factors in total placenta
      and different trophoblast cell models. Immunohistochemistry of placental tissues
      and differentiating villous explant cultures showed that expression of TCF-3/4
      strongly increased in invading trophoblasts. Some of these cells also accumulated
      dephosphorylated beta-catenin in the nucleus. Wnt3A treatment of primary
      cytotrophoblasts and SGHPL-5 cells induced activity of TCF-luciferase reporters.
      Accordingly, the ligand provoked interaction of TCF-3/4 with beta-catenin as
      assessed in electrophoretic mobility shift assays (EMSAs) and up-regulation of
      Wnt/TCF target genes as observed by Western blot analyses. Wnt3A stimulated
      trophoblast migration and invasion through Matrigel, which could be blocked by
      addition of Dickkopf-1, mediating in-hibition of canonical Wnt signaling.
      Dickkopf-1 also reduced basal migration, invasion, and proliferation of
      cytotrophoblasts, suggesting expression of endogenous Wnt ligand(s).
      Immunohistochemistry revealed that the percentage of extravillous trophoblasts
      containing nuclear beta-catenin was significantly higher in placentas of complete
      hydatidiform mole pregnancies as compared to normal placentas. Thus, canonical
      Wnt signaling may promote invasive trophoblast differentiation, and exaggerated
      activation of the path-way could contribute to trophoblastic hyperplasia and
      local invasion.

PMID- 16565490
TI  - Impairment of the intestinal barrier by ethanol involves enteric microflora and
      mast cell activation in rodents.
AB  - Alcohol hepatic toxicity in heavy drinkers is associated with high endotoxin
      blood levels and increased intestinal permeability. Because endotoxins can cross
      damaged mucosa, we investigated the mechanisms through which ethanol impairs the
      colonic epithelium of rats submitted to acute alcohol intake. Colonic
      permeability to (51)Cr-ethylenediamintetraacetic acid was increased 24 hours
      after 3.0 g/kg ethanol intake (3.2 +/- 0.2% versus 2.2 +/- 0.2%) and was
      associated with significant endotoxemia. Antibiotics and doxantrazole (a mast
      cell membrane stabilizer) significantly inhibited the effect of ethanol. Two
      hours after intake, plasma concentrations of ethanol were twofold higher in
      antibiotic-treated rats than in controls (155.8 +/- 9.3 mg/dl versus 75.7 +/- 7.6
      mg/dl, P < 0.001). Lumenal concentrations of acetaldehyde were markedly increased
      after ethanol intake (132.6 +/- 31.6 micromol/L versus 20.8 +/- 1.4 micromol/L, P
      < 0.05) and antibiotics diminished this increase (86.2 +/- 10.9 micromol/L). In
      colonic samples mounted in Ussing chambers, acetaldehyde but not ethanol
      increased dextran flux across the mucosa by 54%. Doxantrazole inhibited the
      effect of acetaldehyde. This study demonstrates that an acute and moderate
      ethanol intake alters the epithelial barrier through ethanol oxidation into
      acetaldehyde by the colonic microflora and downstream mast cell activation. Such
      alterations that remain for longer periods could result in excessive endotoxin
      passage, which could explain the subsequent endotoxemia frequently observed in
      patients with alcoholic liver disease.

PMID- 16565491
TI  - Possible regulation of migration of intrahepatic cholangiocarcinoma cells by
      interaction of CXCR4 expressed in carcinoma cells with tumor necrosis factor
      alpha and stromal-derived factor-1 released in stroma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is highly fatal because of early invasion,
      widespread metastasis, and lack of an effective therapy. We examined roles of
      CXCR4 and its ligand, stromal cell-derived factor (SDF)-1, in migration of ICC
      with respect to tumor-stromal interaction by using two ICC cell lines, a
      fibroblast cell line (WI-38), and 28 human ICC tissues. The two ICC cell lines
      expressed CXCR4 mRNA and protein, and WI-38 fibroblasts expressed SDF-1 mRNA and
      protein. Migration of cultured ICC cells in Matrigel was induced by co-culture
      with WI-38 fibroblasts and by incubation with SDF-1. Anti-SDF-1 antibody
      suppressed migration, demonstrating that SDF-1 released from WI-38 fibroblasts
      was responsible for this migration. Tumor necrosis factor (TNF)-alpha
      pretreatment of ICC cells up-regulated CXCR4 mRNA and protein expression in a
      concentration-dependent manner. Administration of SDF-1 and TNF-alpha increased
      synergistically ICC cell migration, which was suppressed by the CXCR4 antagonist
      AMD3100. In ICC tissue, TNF-alpha was mainly expressed in infiltrated
      macrophages, CXCR4 in ICC cells, and SDF-1 in stromal fibroblasts. In conclusion,
      the interaction of SDF-1 released from fibroblasts and CXCR4 expressed on ICC
      cells may be actively involved in ICC migration, and TNF-alpha may enhance ICC
      cell migration by increasing CXCR4 expression. CXCR4 could be a therapeutic
      target to prevent ICC invasion.

PMID- 16565493
TI  - Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune
      encephalomyelitis: down-regulation of inflammatory and autoimmune responses.
AB  - Multiple sclerosis (MS) is a disabling inflammatory, autoimmune demyelinating
      disease of the central nervous system. Despite intensive investigation, the
      mechanisms of disease pathogenesis remain unclear, and curative therapies are
      unavailable for MS. The current study describes a possible new strategy for the
      treatment of MS, based on the administration of the vasoactive intestinal peptide
      (VIP), a well-known immunosuppressive neuropeptide. Treatment with VIP
      significantly reduced incidence and severity of experimental autoimmune
      encephalomyelitis (EAE), in a MS-related rodent model system. VIP suppressed EAE
      neuropathology by reducing central nervous system inflammation, including the
      regulation of a wide spectrum of inflammatory mediators, and by selectively
      blocking encephalitogenic T-cell reactivity. Importantly, VIP treatment was
      therapeutically effective in established EAE and prevented the recurrence of the
      disease. Consequently, VIP represents a novel multistep therapeutic approach for
      the future treatment of human MS.

PMID- 16565494
TI  - Protease-activated receptor-2 activation: a major role in the pathogenesis of
      Porphyromonas gingivalis infection.
AB  - We have investigated the specific contribution of protease-activated receptor-2
      (PAR(2)) to host defense during Porphyromonas gingivalis infection. Culture
      supernatants from P. gingivalis strains 33277 and W50 provoked Ca(2+)
      mobilization in cells transfected with PAR(2) (PAR(2)-KNRK) and desensitized the
      subsequent responses to PAR(2)-selective agonist. In addition, culture
      supernatants of P. gingivalis E8 (RgpA/RgpB double knockout) did not cause
      calcium response in PAR(2)-KNRK cells, evidencing the involvement of the arginine
      specific cysteine proteases RgpA and RgpB in PAR(2) activation by P. gingivalis.
      Injection of P. gingivalis into mouse subcutaneous chambers provoked an increased
      proteolytic activity, which was inhibited by serine protease inhibitors. Fluids
      collected from chambers of P. gingivalis-injected mice were able to activate
      PAR(2) and this activation was inhibited by serine protease inhibitors. P.
      gingivalis inoculation into subcutaneous chambers of wild-type mice induced an
      inflammatory response that was inhibited by a serine protease inhibitor and was
      significantly reduced in PAR(2)-deficient mice. Finally, mice orally challenged
      with P. gingivalis developed alveolar bone loss, which was significantly reduced
      in PAR(2)-deficient mice at 42 and 60 days after P. gingivalis infection. We
      conclude that PAR(2) is activated on P. gingivalis infection, in which it plays
      an important role in the host inflammatory response.

PMID- 16565492
TI  - Kupffer cell-dependent hepatitis occurs during influenza infection.
AB  - Respiratory infections, including influenza in humans, are often accompanied by a
      hepatitis that is usually mild and self-limiting. The mechanism of this kind of
      liver damage is not well understood. In the present study, we show that influenza
      associated hepatitis occurs due to the formation of inflammatory foci that
      include apoptotic hepatocytes, antigen-specific CD8(+) T cells, and Kupffer
      cells. Serum aminotransaminase levels were elevated, and both the histological
      and serum enzyme markers of hepatitis were increased in secondary influenza
      infection, consistent with a primary role for antigen-specific T cells in the
      pathogenesis. No virus could be detected in the liver, making this a pure example
      of "collateral damage" of the liver. Notably, removal of the Kupffer cells
      prevented the hepatitis. Such hepatic collateral damage may be a general
      consequence of expanding CD8(+) T-cell populations during many extrahepatic viral
      infections, yielding important implications for liver pathobiology.

PMID- 16565496
TI  - Maternal antibodies enhance or prevent cytomegalovirus infection in the placenta
      by neonatal Fc receptor-mediated transcytosis.
AB  - How human cytomegalovirus (CMV) reaches the fetus across the placenta is unknown.
      The major viral cause of congenital disease, CMV infects the uterine-placental
      interface with varied outcomes depending on the strength of maternal humoral
      immunity and gestational age. Covering the surface of villi that float in blood,
      syncytiotrophoblasts express the neonatal Fc receptor (FcRn) that transports IgG
      for passive immunity. Immunohistochemical analysis of early-gestation biopsy
      specimens showed an unusual pattern of CMV replication proteins in underlying
      villus cytotrophoblasts, whereas syncytiotrophoblasts were spared. Found in
      placentas with low to moderate CMV-neutralizing antibody titers, this pattern
      suggested virion transcytosis across the surface. In contrast,
      syncytiotrophoblasts from placentas with high neutralizing titers contained viral
      DNA and caveolin-1-positive vesicles in which IgG and CMV glycoprotein B co
      localized. In villus explants, IgG-virion transcytosis and macrophage uptake were
      blocked with trypsin-treatment and soluble protein A. Quantitative analysis in
      polarized epithelial cells showed that FcRn-mediated transcytosis was blocked by
      the Fc fragment of IgG, but not F(ab')(2). Our results suggest that CMV virions
      could disseminate to the placenta by co-opting the receptor-mediated transport
      pathway for IgG. These findings could explain the efficacy of hyperimmune IgG for
      treatment of primary CMV infection during gestation and support vaccination.

PMID- 16565495
TI  - A tumor necrosis factor receptor 1-dependent conversation between central nervous
      system-specific T cells and the central nervous system is required for
      inflammatory infiltration of the spinal cord.
AB  - We examined the role of tumor necrosis factor receptor 1 (TNFR1) in inflammation
      initiated by the adoptive transfer of central nervous system (CNS)-specific Th1
      cells in experimental autoimmune encephalomyelitis, a murine model of multiple
      sclerosis. This adoptive transfer paradigm eliminates the confounding effects of
      bacterial adjuvants in the analysis of inflammation. We found that although T
      cells could reach the meninges and perivascular space in the absence of TNFR1,
      recruitment of other inflammatory cells from the blood was dramatically reduced.
      The reduction in the recruitment of CD11b(hi) cells correlated with a dramatic
      reduction in the production of the chemokines CCL2 (MCP-1) and CXLC2 (MIP-2) in
      TNFR1-deficient hosts. Bone marrow chimera experiments demonstrated that TNF can
      be effectively supplied by either the hematopoietic system or the CNS, but the
      essential TNFR1-responsive cells reside in the CNS. Previous work has
      demonstrated that microglia produce CCL2, and here we demonstrate that astrocytes
      and endothelial cells produced CXCL2 in the early stages of inflammation.
      Therefore, productive inflammation results from a conversation, or mutually
      responding signals, between the initiating T cells and cells in the parenchyma of
      the spinal cord.

PMID- 16565497
TI  - Type I interferon production by tertiary lymphoid tissue developing in response
      to 2,6,10,14-tetramethyl-pentadecane (pristane).
AB  - Lymphoid neogenesis is associated with antibody-mediated autoimmune diseases such
      as Sjogren's syndrome and rheumatoid arthritis. Although systemic lupus
      erythematosus is the prototypical B-cell-mediated autoimmune disease, the role of
      lymphoid neogenesis in its pathogenesis is unknown. Intraperitoneal injection of
      2,6,10,14-tetramethyl-pentadecane (TMPD, pristane) or mineral oil causes
      lipogranuloma formation in mice, but only TMPD-treated mice develop lupus. We
      report that lipogranulomas are a form of lymphoid neogenesis. Immunoperoxidase
      staining of lipogranulomas revealed B cells, CD4(+) T cells, and dendritic cells
      and in some cases organization into T- and B-cell zones. Lipogranulomas also
      expressed the lymphoid chemokines CCL21, CCL19, CXCL13, CXCL12, and CCL22.
      Expression of the type I interferon (IFN-I)-inducible genes Mx1, IRF7, IP-10, and
      ISG-15 was greatly increased in TMPD- versus mineral oil-induced lipogranulomas.
      Dendritic cells from TMPD lipogranulomas underwent activation/maturation with
      high CD86 and interleukin-12 expression. Magnetic bead depletion of dendritic
      cells markedly diminished IFN-inducible gene (Mx1) expression. We conclude that
      TMPD-induced lupus is associated with the formation of ectopic lymphoid tissue
      containing activated dendritic cells producing IFN-I and interleukin-12. In view
      of the increased IFN-I production in systemic lupus erythematosus, these studies
      suggest that IFN-I from ectopic lymphoid tissue could play a role in the
      pathogenesis of experimental lupus in mice.

PMID- 16565498
TI  - Deficiency of C4 from donor or recipient mouse fails to prevent renal allograft
      rejection.
AB  - Complement effector products generated in the transplanted kidney are known to
      mediate transplant rejection, but which of the three main activation pathways of
      complement trigger this response is unclear. Here we assessed the role of the
      classical and lectin pathways by studying the common component C4 in mouse kidney
      transplant rejection. We transplanted wild-type or C4-null H-2(b) donor kidneys
      into H-2(k) or H-2(d) recipients, or vice-versa, to assess the roles of donor
      kidney and recipient expression of complement. Intragraft C4 gene expression rose
      substantially during rejection. However, we found no significant association
      between graft acceptance and the presence of C4 in either the donor kidney or
      recipient mouse. At the time of rejection, we found no significant differences in
      alloantibody response in the different groups. Tubular deposition of C3 to C9
      occurred regardless of the absence or presence of C4 in either the donor or
      recipient mouse, indicating that C4 was dispensable for complement activation at
      this site. These data suggest that complement activation and renal allograft
      rejection are independent of the classical and lectin pathways in these models,
      implying that in the absence of these pathways the alternative pathway is the
      main trigger for complement-mediated rejection.

PMID- 16565499
TI  - Trehalose 6,6'-dimycolate and lipid in the pathogenesis of caseating granulomas
      of tuberculosis in mice.
AB  - Trehalose 6,6'-dimycolate (TDM) is the most abundant, most granulomagenic, and
      most toxic lipid extractable from the surface of virulent Mycobacterium
      tuberculosis (MTB). We further examined its toxicity, which requires activation
      by oily surfaces. Injections of MTB and/or TDM into sensitized mice induced
      caseating granulomas that centered on oil droplets. If large doses of MTB were
      injected in saline, caseating granulomas developed in adipose tissue, but MTB
      with surface TDM removed induced only acute inflammation that did not persist.
      Variations in protocols produced several variants of caseating granulomas, each
      with characteristics of human tuberculosis. In each instance, MTB were localized
      in fat cells or oil drops during initiation of caseating granulomas suggesting
      that necrosis was caused by activation of the toxicity of TDM toxicity. Evidence
      extending these findings to the lung was derived from the observation that in
      sensitized mice, as in humans, tuberculosis development stimulates accumulation
      of lipid selectively in alveoli. MTB preferentially associated with lipid
      droplets in developing necrotic foci in late-stage murine tuberculosis. This
      supports the hypothesis that pulmonary tuberculosis sequesters MTB in a protected
      environment that accumulates lipid until it is able to activate the toxicity of
      TDM and initiate necrosis that results in caseating granulomas.

PMID- 16565500
TI  - The Ret(C620R) mutation affects renal and enteric development in a mouse model of
      Hirschsprung's disease.
AB  - In rare families RET tyrosine kinase receptor substitutions located in exon 10
      (especially at positions 609, 618, and 620) can concomitantly cause the MEN 2A
      (multiple endocrine neoplasia type 2A) or FMTC (familial medullary thyroid
      carcinoma) cancer syndromes, and Hirschsprung's disease (HSCR). No animal model
      mimicking the co-existence of the MEN 2 pathology and HSCR is available, and the
      association of these activating mutations with a developmental defect still
      represents an unresolved problem. The aim of this work was to investigate the
      significance of the RET(C620R) substitution in the pathogenesis of both gain- and
      loss-of-function RET-associated diseases. We report the generation of a line of
      mice carrying the C620R mutation in the Ret gene. Although Ret(C620R) homozygotes
      display severe defects in kidney organogenesis and enteric nervous system
      development leading to perinatal lethality. Ret(C620R) heterozygotes recapitulate
      features characteristic of HSCR including hypoganglionosis of the
      gastrointestinal tract. Surprisingly, heterozygotes do not show any defects in
      the thyroid that might be attributable to a gain-of-function mutation. The
      Ret(C620R) allele is responsible for HSCR and affects the development of kidneys
      and the enteric nervous system (ENS). These mice represent an interesting model
      for studying new therapeutic approaches for the treatment of HSCR disease.

PMID- 16565501
TI  - Sarcolemmal damage in dystrophin deficiency is modulated by synergistic
      interactions between mechanical and oxidative/nitrosative stresses.
AB  - Dystrophin deficiency is the cause of Duchenne muscular dystrophy, but the
      precise physiological basis for muscle necrosis remains unclear. To determine
      whether dystrophin-deficient muscles are abnormally susceptible to oxidative and
      nitric oxide (NO)-driven tissue stress, a hindlimb ischemia/reperfusion (I/R)
      model was used. Dystrophic mdx mice exhibited abnormally high levels of lipid
      peroxidation and protein nitration, which were preceded by exaggerated NO
      production during ischemia. Visualization of NO with the fluorescent probe 4,5
      diaminofluorescein diacetate suggested that excess NO production during ischemia
      occurred within a subset of mdx fibers. In mdx muscles only, prior exposure to
      I/R dramatically increased the level of sarcolemmal damage resulting from stretch
      mediated mechanical stress, indicating greatly exacerbated hyperfragility of the
      dystrophic fiber membrane. Treatment with NO synthase inhibitors (l-N(G)
      nitroarginine methyl ester hydrochloride or 7-nitroindazol) effectively blocked
      the synergistic interaction between I/R and mechanical stress-mediated
      sarcolemmal damage under these conditions. Taken together, our findings provide
      direct ex-perimental evidence that several prevailing hy-potheses regarding the
      cause of muscle fiber damage in dystrophin-deficient muscle can be integrated
      into a common pathophysiological framework involving interactions between
      oxidative stress, ab-normal NO regulation, and hyperfragility of the sarcolemma.

PMID- 16565502
TI  - ADP-ribosylation factor-like 3 is involved in kidney and photoreceptor
      development.
AB  - ADP-ribosylation factor-like 3 (Arl3) is a member of a small subfamily of G
      proteins involved in membrane-associated vesicular and intracellular trafficking
      processes. Genetic studies in Leishmania have shown that the Arl3 homolog is
      essential for flagellum biogenesis. Mutations in a related human family member,
      Arl6, result in Bardet-Biedl syndrome in humans, which is characterized by
      genital, renal, and retinal abnormalities, obesity, and learning deficits. As
      part of our large-scale phenotypic screen, mice deficient for the Arl3 gene were
      generated and analyzed. Arl3 (-/-) mice were born at a sub-Mendelian ratio, were
      small and sickly, and had markedly swollen abdomens. These mutants failed to
      thrive, and all died by 3 weeks of age. The (-/-) mice exhibited abnormal
      development of renal, hepatic, and pancreatic epithelial tubule structures, which
      is characteristic of the renal-hepatic-pancreatic dysplasia found in autosomal
      recessive polycystic kidney disease. Absence of Arl3 was associated with abnormal
      epithelial cell proliferation and cyst formation. Moreover, mice lacking Arl3
      exhibited photoreceptor degeneration as early as postnatal day 14. These results
      are the first to implicate Arl3 in a ciliary disease affecting the kidney,
      biliary tract, pancreas, and retina.

PMID- 16565504
TI  - Generalized lysosome-associated membrane protein-2 defect explains multisystem
      clinical involvement and allows leukocyte diagnostic screening in Danon disease.
AB  - Danon disease, an X-linked dominant disorder, results from mutations in the
      lysosome-associated membrane protein-2 (LAMP2) gene and presents with
      hypertrophic cardiomyopathy, skeletal myopathy, and mental retardation. To
      investigate the effects of LAMP2 gene mutations on protein expression in
      different tissues, we screened LAMP2 gene mutations and LAMP-2 protein deficiency
      in the skeletal muscle of nine unrelated patients with hypertrophic
      cardiomyopathy and vacuolar myopathy. We identified three novel families
      (including one affected mother) with unreported LAMP2 gene null mutations and
      LAMP-2 protein deficiency in skeletal and myocardial muscle, leukocytes, and
      fibroblasts. LAMP-2 protein deficiency was detectable in various tissues,
      including leukocytes, explaining the multisystem clinical involvement. Skeletal
      muscle immunopathology showed that mutant protein was not localized in the Golgi
      complex, vacuolar membranes expressed sarcolemmal-specific proteins, and the
      degree of muscle fiber vacuolization correlated with clinical muscle involvement.
      In our female patient, muscle histopathology and LAMP-2 protein analysis was
      inconclusive, indicating that diagnosis in females requires mutation
      identification. The random X-chromosome inactivation found in muscle and
      leukocytes excluded the possibility that selective involvement of some tissues in
      females is due to skewed X-chromosome inactivation. Therefore, biochemical
      analysis of leukocytes might be used for screening in male patients, but genetic
      screening is required in females.

PMID- 16565503
TI  - Mutant fibrinogen cleared from the endoplasmic reticulum via endoplasmic
      reticulum-associated protein degradation and autophagy: an explanation for liver
      disease.
AB  - The endoplasmic reticulum (ER) quality control processes recognize and remove
      aberrant proteins from the secretory pathway. Several variants of the plasma
      protein fibrinogen are recognized as aberrant and degraded by ER-associated
      protein degradation (ERAD), thus leading to hypofibrinogenemia. A subset of
      patients with hypofibrinogenemia exhibit hepatic ER accumulation of the variant
      fibrinogens and develop liver cirrhosis. One such variant named Aguadilla has a
      substitution of Arg375 to Trp in the gamma-chain. To understand the cellular
      mechanisms behind clearance of the aberrant Aguadilla gamma-chain, we expressed
      the mutant gammaD domain in yeast and found that it was cleared from the ER via
      ERAD. In addition, we discovered that when ERAD was saturated, aggregated
      Aguadilla gammaD accumulated within the ER while a soluble form of the
      polypeptide transited the secretory pathway to the trans-Golgi network where it
      was targeted to the vacuole for degradation. Examination of Aguadilla gammaD in
      an autophagy-deficient yeast strain showed stabilization of the aggregated ER
      form, indicating that these aggregates are normally cleared from the ER via the
      autophagic pathway. These findings have clinical relevance in the understanding
      of and treatment for ER storage diseases.

PMID- 16565505
TI  - Peroxisomal multifunctional protein-2 deficiency causes motor deficits and glial
      lesions in the adult central nervous system.
AB  - In humans, mutations inactivating multifunctional protein-2 (MFP-2), and thus
      peroxisomal beta-oxidation, cause neuronal heterotopia and demyelination, which
      is clinically reflected by hypotonia, seizures, and death within the first year
      of life. In contrast, our recently generated MFP-2-deficient mice did not show
      neurodevelopmental abnormalities but exhibited aberrations in bile acid
      metabolism and one of three of them died early postnatally. In the postweaning
      period, all survivors developed progressive motor deficits, including abnormal
      cramping reflexes of the limbs and loss of mobility, with death at 6 months.
      Motor impairment was not accompanied by lesions of peripheral nerves or muscles.
      However, in the central nervous system MFP-2-deficient mice overexpressed
      catalase in glial cells, accumulated lipids in ependymal cells and in the
      molecular layer of the cerebellum, exhibited severe astrogliosis and reactive
      microglia predominantly within the gray matter of the brain and the spinal cord,
      whereas synaptic and myelin markers were not affected. This culminated in
      degenerative changes of astroglia cells but not in overt neuronal lesions.
      Neither the motor deficits nor the brain lesions were aggravated by increasing
      the branched-chain fatty acid concentration through dietary supplementation.
      These data indicate that MFP-2 deficiency in mice causes a neurological phenotype
      in adulthood that is manifested primarily by astroglial damage.

PMID- 16565506
TI  - Alcohol abuse enhances neuroinflammation and impairs immune responses in an
      animal model of human immunodeficiency virus-1 encephalitis.
AB  - Neuroinflammatory disorders (including human immunodeficiency virus-1
      encephalitis, HIVE) are associated with oxidative stress and inflammatory brain
      injury, and excessive alcohol use can exacerbate tissue damage. Using a murine
      model of HIVE, we investigated the effects of alcohol abuse on the clearance of
      virus-infected macrophages and neuroinflammation. Severe combined immunodeficient
      mice were reconstituted with human lymphocytes, and encephalitis was induced by
      intracranial injection of HIV-1-infected monocyte-derived macrophages (HIV-1(+)
      MDM). Animals were fed an ethanol-containing diet beginning 2 weeks before
      lymphocyte engraftment and for the entire duration of the experiment. Lymphocyte
      engraftment was not altered by ethanol exposure. Alcohol-mediated
      immunosuppression in ethanol-fed mice was manifested by a significant decrease in
      CD8(+)/interferon-gamma(+) T lymphocytes, a fivefold increase in viremia, and
      diminished expression of immunoproteasomes in the spleen. Although both groups
      showed similar amounts of CD8(+) T-lymphocyte infiltration in brain areas
      containing HIV-1(+) MDMs, ethanol-fed mice featured double the amounts of HIV
      1(+) MDMs in the brain compared to controls. Ethanol-exposed mice demonstrated
      higher microglial reaction and enhanced oxidative stress. Alcohol exposure
      impaired immune responses (increased viremia, decreased immunoproteasome levels,
      and prevented efficient elimination of HIV-1(+) MDMs) and enhanced
      neuroinflammation in HIVE mice. Thus, alcohol abuse could be a co-factor in
      progression of HIV-1 infection of the brain.

PMID- 16565507
TI  - Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell
      proliferation and anchorage-independent growth.
AB  - The aquaporins represent a family of transmembrane water channel proteins that
      play a major role in trans-cellular and transepithelial water movement. Most
      tumors have been shown to exhibit high vascular permeability and interstitial
      fluid pressure, but the transport pathways for water within tumors remain
      unknown. Here, we tested 10 non-small cell lung cancer cell lines of various
      origins by reverse transcriptase-polymerase chain reaction and Western blot
      analysis and identified clear expression of aquaporin 1 (AQP1) in seven cell
      lines. We next examined the distribution of the AQP1 protein in several types of
      primary lung tumors (16 squamous cell carcinomas, 21 adenocarcinomas, and 7
      bronchoalveolar carcinomas) by immunohistochemical staining. AQP1 was
      overexpressed in 62% (13 of 21) and 75% (6 of 8) of adenocarcinoma and
      bronchoalveolar carcinoma, respectively, whereas all cases of squamous cell
      carcinoma and normal lung tissue were negative. Forced expression of full-length
      AQP1 cDNA in NIH-3T3 cells induced many phenotypic changes characteristic of
      transformation, including cell proliferation-enhancing activity by the MTT assay
      and anchorage-independent growth in soft agar. Although further details on the
      molecular function of AQP1 related to tumorigenesis remain to be elucidated, our
      results suggest a potential role of AQP1 as a novel therapeutic target for the
      management of lung cancer.

PMID- 16565508
TI  - A novel aspartic proteinase-like gene expressed in stratified epithelia and
      squamous cell carcinoma of the skin.
AB  - Homeostasis of stratified epithelia, such as the epidermis of the skin, is a
      sophisticated process that represents a tightly controlled balance between
      proliferation and differentiation. Alterations of this balance are associated
      with common human diseases including cancer. Here, we report the cloning of a
      novel cDNA sequence, from mouse back skin, that is induced by the phorbol ester
      12-O-tetradecanoylphorbol-13-acetate (TPA) and codes for a hitherto unknown
      aspartic proteinase-like protein (Taps). Taps represents a potential AP-1 target
      gene because TPA-induced expression in epidermal keratinocytes critically depends
      on c-Fos, and co-treatment with dexamethasone, a potent inhibitor of AP-1
      mediated gene regulation, resulted in impaired activation of Taps expression.
      Taps mRNA and protein are restricted to stratified epithelia in mouse embryos and
      adult tissues, implicating a crucial role for this aspartic proteinase-like gene
      in differentiation and homeostasis of multilayered epithelia. During chemically
      induced carcinogenesis, transient elevation of Taps mRNA and protein levels was
      detected in benign skin tumors. However, its expression is negatively associated
      with dedifferentiation and malignant progression in squamous cell carcinomas of
      the skin. Similar expression was observed in squamous skin tumors of patients,
      suggesting that detection of Taps levels represents a novel strategy to
      discriminate the progression state of squamous skin cancers.

PMID- 16565509
TI  - Prolactin potentiates transforming growth factor alpha induction of mammary
      neoplasia in transgenic mice.
AB  - Prolactin influences mammary development and carcinogenesis through endocrine and
      autocrine/paracrine mechanisms. In virgin female mice, pro-lactin overexpression
      under control of a mammary selective nonhormonally responsive promoter, neu
      related lipocalin, results in estrogen receptor alpha (ERalpha)-positive and
      ERalpha-negative adenocarcinomas. However, disease in vivo occurs in the context
      of dysregulation of multiple pathways. In this study, we investigated the ability
      of prolactin to modulate carcinogenesis when co-expressed with the potent
      oncogene transforming growth factor alpha (TGFalpha) in bitransgenic mice.
      Prolactin and TGFalpha cooperated to reduce dramatically the latency of mammary
      macrocyst development, the principal lesion type induced by TGFalpha. In
      combination, prolactin and TGFalpha also increased the incidence and reduced the
      latency of other preneoplastic lesions and increased cellular turnover in
      structurally normal alveoli and ducts compared with single transgenic females.
      Bitransgenic glands contained higher levels of phosphorylated ERK1/2 compared
      with single TGFalpha transgenic glands, suggesting that this kinase may be a
      point of signaling crosstalk. Furthermore, transgenic prolactin also reversed the
      decrease in ERalpha induced by neu-related lipocalin-TGFalpha. Our findings
      demonstrate that locally produced prolactin can strikingly potentiate the
      carcinogenic actions of another oncogene and modify ovarian hormone
      responsiveness, suggesting that prolactin signaling may be a potential
      therapeutic target.

PMID- 16565510
TI  - Epigenetic instability and chromosomal instability in hepatocellular carcinoma.
AB  - The aim of this study was to clarify the association between the epigenetic
      instability phenotype and the chromosomal instability phenotype in primary
      hepatocellular carcinoma (HCC). Sixty primary HCC tumors were examined.
      Methylation status for nine CpG islands (the p16, COX2, GSTP1, RASSF1A, E
      cadherin, and APC gene promoters, and the MINT 1, 25, and 31 clones) was
      evaluated by methylation-specific polymerase chain reaction. Chromosomal
      structural alterations of these 60 HCC tumors were characterized in our previous
      study by using whole genomic array-based comparative genomic hybridization. We
      found that the epigenetic instability phenotype and the chromosomal instability
      phenotype are not mutually exclusive in hepatocarcinogenesis and that they do not
      show a simple cause-and-effect relationship. Hepatitis virus infection in the
      background liver was significantly associated with these instability phenotypes.
      Furthermore, we identified an epigenetic instability-dependent HCC that shows
      frequent epigenetic aberrations without chromosomal instability. It was
      noteworthy that epigenetic instability-positive and -negative HCCs displayed
      distinctive combinations of chromosomal structural alterations. In summary, by
      combined analyses of genetic and epigenetic aberration profiles in HCC, we
      obtained a comprehensive view of genomic alterations in hepatocarcinogenesis. Our
      results have clinical relevance because epigenetic instability-dependent HCCs may
      respond well to methylation inhibitory therapies.

PMID- 16565511
TI  - Up-regulated expression of the CXCR2 ligand KC/GRO-alpha in atherosclerotic
      lesions plays a central role in macrophage accumulation and lesion progression.
AB  - Macrophage-mediated inflammation is central to atherogenesis. We have determined
      previously that the CXC chemokine receptor CXCR2 is involved in advanced
      atherosclerosis. We sought to determine whether one of the ligands of CXCR2,
      KC/GRO-alpha, can also modulate atherogenesis. KC/GRO-alpha(-/-) mice were
      generated and mated with the atherosclerosis-prone LDLR(-/-) mice. There was a
      significant reduction in atherosclerosis in mice lacking KC/GRO-alpha; however,
      this reduction was only approximately half that seen previously in mice lacking
      CXCR2 in the leukocyte. To determine whether CXCR2 is involved in the early
      formation of atherosclerosis, leukocyte-specific CXCR2(-/-) chimeric mice on
      LDLR(-/-) background were generated. Early fatty streak lesion formation in these
      mice was not affected by leukocyte CXCR2 deficiency whereas lesions were less
      developed in mice lacking leukocyte CXCR2 when atherosclerosis was allowed to
      progress to the intermediate stage. Macrophages were relatively sparse in the
      lesions of leukocyte CXCR2(-/-) mice despite robust MCP-1 expression. These
      studies indicate that KC/GRO-alpha/CXCR2 does not play a critical role in
      recruitment of macrophages into early atherosclerotic lesions but both arterial
      KC/GRO-alpha and leukocyte-specific CXCR2 expression are central to macrophage
      accumulation in established fatty streak lesions.

PMID- 16565512
TI  - Interleukin-1beta and signaling of interleukin-1 in vascular wall and circulating
      cells modulates the extent of neointima formation in mice.
AB  - Interleukin (IL)-1 is an important mediator of inflammation and cardiovascular
      disease. Here, we examined the role of IL-1 in arterial neointima formation.
      Carotid artery neointima was induced by ligation, and arteries were harvested 4
      weeks after injury. The neointima/media of mice deficient in the IL-1 signaling
      receptor (IL-1R1(-/-)) was significantly reduced compared to IL-1R1(+/+) controls
      (P < 0.01). IL-1R1(+/+) mice receiving subcutaneous IL-1ra also had significantly
      reduced neointima/media compared with placebo (P < 0.05). IL-1beta(-/-) mice had
      reduced neointima/media compared to wild-type (P < 0.05), whereas IL-1alpha(-/-)
      mice were no different from controls. Mice deficient in the P2X(7) receptor
      (involved in IL-1 release) or caspase-1 (involved in IL-1 activation) did not
      differ in their response to carotid ligation compared to controls. To examine the
      site of IL-1 signaling, we generated chimeric mice. IL-1R1(+/+) mice receiving IL
      1R1(-/-) marrow and IL-1R1(-/-) mice receiving IL-1R1(+/+) marrow both had
      significantly reduced neointima/media compared with IL-1R1(+/+) to IL-1R1(+/+) (P
      < 0.05) but had significantly greater neointima/media than IL-1R1(-/-) to IL-1R1(
      /-) controls (P < 0.05). These data confirm the importance of IL-1beta signaling
      in mediating arterial neointima formation and suggest the involvement of IL-1
      signaling in both circulating and arterial wall cells. Furthermore, receptor
      antagonism may be a better therapeutic target than interruption of IL-1beta
      processing or release.

PMID- 16565513
TI  - Metallothionein-1 and -2 expression in cadmium- or arsenic-derived human
      malignant urothelial cells and tumor heterotransplants and as a prognostic
      indicator in human bladder cancer.
AB  - The goal of this study was to determine if the expression of the metallothionein
      (MT)-1/2 proteins might serve as a biomarker for the development of bladder
      cancer. A retrospective analysis of MT-1/2 staining was performed on 343 tissue
      sections from patients referred for the diagnosis of bladder cancer. The
      specimens were subdivided into six categories: benign, dysplastic, low-grade
      cancer, high-grade cancer with no evidence of invasion, high-grade cancer with
      evidence of invasion, and carcinoma in situ. There was no expression of MT-1/2 in
      benign lesions and low-grade cancers, a low incidence of expression in dysplastic
      lesions and high-grade cancers with no evidence of muscle invasion, and a
      significantly increased incidence of MT-1/2 in high-grade cancers that had
      invaded the underlying matrix. The expression of MT-1/2 varied in intensity from
      sample to sample and was focal in its expression. It was concluded from these
      findings that MT-1/2 may be a prognostic marker for cancers that are progressing
      to invade the underlying stroma of the bladder wall. The expression of MT-1/2 was
      also determined in a cell culture model of human urothelium that had been
      malignantly transformed by Cd2+ and As3+ and shown to be capable of tumor
      formation in nude mice. It was demonstrated that the expression of MT-1/2 in the
      tumor heterotransplants was similar to the pattern found in archival specimens of
      high-grade bladder cancers. The MT-1/2 staining in the heterotransplants was
      focal in pattern, varied in intensity, and highest in the less differentiated
      cells of the tumor. These findings indicate that the cell culture model may serve
      to help define the role of MT-1/2 expression in bladder cancer invasion.

PMID- 16565514
TI  - Identification of new human pregnane X receptor ligands among pesticides using a
      stable reporter cell system.
AB  - Pregnane X receptor (PXR, NR1I2) is activated by various chemically unrelated
      compounds, including environmental pollutants and drugs. We proceeded here to in
      vitro screening of 28 pesticides with a new reporter system that detects human
      pregnane X receptor (hPXR) activators. The cell line was obtained by a two-step
      stable transfection of cervical cancer HeLa cells. The first transfected cell
      line, HG5LN, contained an integrated luciferase reporter gene under the control
      of a GAL4 yeast transcription factor-binding site. The second cell line HGPXR was
      derived from HG5LN and stably expressed hPXR ligand-binding domain fused to GAL4
      DNA-binding domain (DBD). The HG5LN cells were used as a control to detect
      nonspecific activities. Pesticides from various chemical classes were
      demonstrated, for the first time, to be hPXR activators: (1) herbicides:
      pretilachlor, metolachlor, and alachlor chloracetanilides, oxadiazon oxiconazole,
      and isoproturon urea; (2) fungicides: bupirimate and fenarimol pyrimidines,
      propiconazole, fenbuconazole, prochloraz conazoles, and imazalil triazole; and
      (3) insecticides: toxaphene organochlorine, permethrin pyrethroid, fipronil
      pyrazole, and diflubenzuron urea. Pretilachlor, metolachlor, bupirimate, and
      oxadiazon had an affinity for hPXR equal to or greater than the positive control
      rifampicin. Some of the newly identified hPXR activators were also checked for
      their ability to induce cytochrome P450 3A4 expression in a primary culture of
      human hepatocytes. HGPXR, with HG5LN as a reference, was grafted onto nude mice
      to assess compound bioavailability through in vivo quantification of hPXR
      activation. Altogether, our data indicate that HGPXR cells are an efficient tool
      for identifying hPXR ligands and establishing pesticides as hPXR activators.

PMID- 16565516
TI  - Localization of sites of interaction between p23 and Hsp90 in solution.
AB  - The co-chaperone p23 forms a complex with the chaperone Hsp90 that mediates the
      folding pathway leading to the production of functional steroid receptors.
      Solution NMR spectroscopy has been used to characterize sites of interaction
      between Hsp90 and p23. Titration of p23 with Hsp90 results in the selective
      broadening of certain cross-peaks in the 15N-1H heteronuclear single quantum
      correlation (HSQC) spectrum. The interaction sites on p23 and Hsp90 have been
      localized by dissection of Hsp90 into single-domain and two-domain constructs.
      The N-terminal (N) domain of Hsp90 does not affect the NMR spectrum of p23 either
      in the presence or absence of the ATP analogue ATPgammaS. Similarly, the HSQC
      spectrum of 15N-labeled N domain is unperturbed by the addition of p23. A subset
      of cross-peaks in the HSQC spectrum of p23 is shifted upon addition of the middle
      (M) domain of Hsp90, and the same shifts are observed upon the addition of the
      two-domain construct containing the N and M domains (NM). The addition of the co
      chaperone Aha1, which is known to bind to the M domain of Hsp90, displaces p23
      from Hsp90. The resonances that shift upon addition of the M and NM Hsp90
      constructs correspond to those that were broadened at the lowest ratios of full
      length Hsp90 to p23 and define an Hsp90 binding site that includes much of the C
      terminal sequence of p23 together with a contiguous beta-hairpin from the N
      terminus. We conclude that p23 forms a specific complex with Hsp90 primarily
      through binding to its middle domain.

PMID- 16565515
TI  - Proteomic identification of a stress protein, mortalin/mthsp70/GRP75: relevance
      to Parkinson disease.
AB  - Functional impairment of mitochondria and proteasomes and increased oxidative
      damage comprise the main pathological phenotypes of Parkinson disease (PD). Using
      an unbiased quantitative proteomic approach, we compared nigral mitochondrial
      proteins of PD patients with those from age-matched controls. 119 of 842
      identified proteins displayed significant differences in their relative abundance
      (increase/decrease) between the two groups. We confirmed that one of these,
      mortalin (mthsp70/GRP75, a mitochondrial stress protein), is substantially
      decreased in PD brains as well as in a cellular model of PD. In addition, nine
      candidate mortalin-binding partners were identified as potential mediators of PD
      pathology. Manipulations of mortalin level in dopaminergic neurons resulted in
      significant changes in sensitivity to PD phenotypes via pathways involving
      mitochondrial and proteasomal function as well as oxidative stress.

PMID- 16565517
TI  - Identification of the key residues responsible for the assembly of
      selenodeiodinases.
AB  - Type I deiodinase is the best characterized member of a small family of
      selenoenzymes catalyzing the bioactivation and disposal of thyroid hormone. This
      enzyme is an integral membrane protein composed of two 27-kDa subunits that
      assemble into a functional enzyme after translation using a highly conserved
      sequence of 16 amino acids in the C-terminal half of the polypeptide,
      (148)DFLXXYIXEAHXXDGW(163). In this study, we used alanine scanning mutagenesis
      to identify the key residues in this domain required for holoenzyme assembly.
      Overexpression of sequential alanine-substituted mutants of a dimerization domain
      green fluorescent protein fusion showed that sequence (152)IYI(154) was required
      for type I enzyme assembly and that a catalytically active monomer was generated
      by a single I152A substitution. Overexpression of the sequential alanine
      substituted dimerization domain mutants in type II selenodeiodinase-expressing
      cells showed that five residues ((153)FLIVY(157)) at the beginning and three
      residues ((164)SDG(166)) at the end of this region were required for the assembly
      of the type II enzyme. In vitro binding analysis revealed a free energy of
      association of -60 +/- 5 kJ/mol for the noncovalent interaction between
      dimerization domain monomers. These data identify and characterize the essential
      residues in the dimerization domain that are responsible for the post
      translational assembly of selenodeiodinases.

PMID- 16565518
TI  - DNA annealing mediated by Rad52 and Rad59 proteins.
AB  - In the budding yeast Saccharomyces cerevisiae, the RAD52 gene is essential for
      all homologous recombination events and its homologue, the RAD59 gene, is
      important for those that occur independently of RAD51. Both Rad52 and Rad59
      proteins can anneal complementary single-stranded (ss) DNA. We quantitatively
      examined the ssDNA annealing activity of Rad52 and Rad59 proteins and found
      significant differences in their biochemical properties. First, and most
      importantly, they differ in their ability to anneal ssDNA that is complexed with
      replication protein A (RPA). Rad52 can anneal an RPA-ssDNA complex, but Rad59
      cannot. Second, Rad59-promoted DNA annealing follows first-order reaction
      kinetics, whereas Rad52-promoted annealing follows second-order reaction
      kinetics. Last, Rad59 enhances Rad52-mediated DNA annealing at increased NaCl
      concentrations, both in the absence and presence of RPA. These results suggest
      that Rad59 performs different functions in the recombination process, and should
      be more accurately viewed as a Rad52 paralogue.

PMID- 16565519
TI  - Thioredoxin reductase 1 deficiency reverses tumor phenotype and tumorigenicity of
      lung carcinoma cells.
AB  - Dietary selenium has potent cancer prevention activity. Both low molecular weight
      selenocompounds and selenoproteins are implicated in this effect. Thioredoxin
      reductase 1 (TR1) is one of the major antioxidant and redox regulators in mammals
      that supports p53 function and other tumor suppressor activities. However, this
      selenium-containing oxidoreductase is also overexpressed in many malignant cells
      and has been proposed as a target for cancer therapy. To further assess the role
      of TR1 in the malignancy process, we used RNA interference technology to decrease
      its expression in mouse lung carcinoma (LLC1) cells. Stable transfection of LLC1
      cells with a small interfering RNA construct that specifically targets TR1
      removal manifested a reversal in the morphology and anchorage-independent growth
      properties of these cancer cells that made them similar to those of normal cells.
      The expression of at least two cancer-related protein mRNAs, Hgf and Opn1, were
      reduced dramatically in the TR1 knockdown cells. Mice injected with the TR1
      knockdown showed a dramatic reduction in tumor progression and metastasis
      compared with those mice injected with the corresponding control vector. In
      addition, tumors that arose from injected TR1 knockdown cells lost the targeting
      construct, suggesting that TR1 is essential for tumor growth in mice. These
      observations provide direct evidence that the reduction of TR1 levels in
      malignant cells is antitumorigenic and suggest that the enzyme is a prime target
      for cancer therapy.

PMID- 16565520
TI  - Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus
      pyogenes is essential for evasion from neutrophils.
AB  - Streptococcus pyogenes is an important pathogen that causes pharyngitis, sepsis,
      and rheumatic fever. Cell-associated streptococcal C5a peptidase (ScpA) protects
      S. pyogenes from phagocytosis and has been suggested to interrupt host defenses
      by enzymatically cleaving complement C5a, a major factor in the accumulation of
      neutrophils at sites of infection. How S. pyogenes recognizes and binds to C5a,
      however, is unclear. We detected a C5a-binding protein in 8 M urea extracts of S.
      pyogenes by ligand blotting using biotinylated C5a. Searching of genome databases
      showed that the C5a-binding protein is identical to the streptococcal plasmin
      receptor (Plr), also known as streptococcal surface dehydrogenase (SDH) and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In the present study we
      identified a novel function of this multifunctional protein. Western blotting and
      immunofluorescence microscopy with anti-Plr/SDH/GAPDH showed that Plr/SDH/GAPDH
      is located on the bacterial surface and released into the culture supernatant.
      Next, we examined whether the streptococcal Plr/SDH/GAPDH inhibits the biological
      effects of C5a on human neutrophils. We found that soluble Plr/SDH/GAPDH inhibits
      C5a-activated chemotaxis and H2O2 production. Furthermore, our results suggested
      that soluble Plr/SDH/GAPDH captures C5a, inhibiting its chemotactic function.
      Also, cell-associated Plr/SDH/GAPDH and ScpA were both necessary for the cleavage
      of C5a on the bacterial surface. Together, these results indicate that the
      multifunctional protein Plr/SDH/GAPDH has additional functions that help S.
      pyogenes escape detection by the host immune system.

PMID- 16565521
TI  - Calcaneal bone mineral density in older patients who have fallen.
AB  - BACKGROUND: Annually, 35-40% of those aged >65 years fall; up to 5% of such falls
      result in fracture. Fracture is determined both by propensity to fall and by bone
      fragility. AIM: To determine osteoporosis prevalence and predictors in patients
      who have fallen. DESIGN: Observational cross-sectional study. METHODS: We
      measured calcaneal BMD in 408 consecutive patients aged >50 years attending after
      falling. Fall number, fracture history, weight, height, and risk factors for
      falls and osteoporosis were recorded. T scores (SD above or below the mean for
      young adults) were derived in both sexes, and Z scores (SD above or below age
      related normal score) in females. RESULTS: In females (n = 300, 74%), mean (SD) T
      score was -1.1(1.6), and mean Z score was 0(1.4); 127 (42%) had osteoporosis (T
      score < - 1.6). ROC curves confirmed significant relationships between
      osteoporosis and age, weight and height (all p < 0.0001). Incorporating fracture
      history, our model (fracture aged >50 years, age >83 years, weight <57 kg, height
      <153 cm as dichotomous variables) predicted osteoporosis with 91% sensitivity,
      34% specificity. Of 108 male fallers, 36 (33%) had osteoporosis. Age, height and
      weight all predicted osteoporosis (p < 0.02). The resulting model (fracture aged
      >50 years, age > or =80 years, weight < or =68 kg, height < or =167 cm as
      dichotomous variables) predicted osteoporosis with 92% sensitivity, 30%
      specificity. DISCUSSION: Osteoporosis prevalence is not increased in female
      fallers compared to age-related norms; empirical use of osteoporosis treatment
      solely on the basis of falls thus appears inappropriate. In both sexes, the
      factors predicting osteoporosis were age, height and weight. Where BMD is not
      practical, possible or economical, our model may be a sensitive means of
      predicting fallers with osteoporosis.

PMID- 16565523
TI  - The descent of man.

PMID- 16565522
TI  - Henoch Schonlein purpura with nephritis in adults: adverse prognostic indicators
      in a UK population.
AB  - BACKGROUND: Henoch Schonlein purpura with nephritis (HSN) in adults may cause
      severe organ injury, but its rarity has contributed to a lack of data. AIM: To
      evaluate clinical outcomes and risk factors in adult HSN patients. DESIGN:
      Retrospective analysis. METHODS: Thirty-seven patients with adult HSN attending
      the Regional Vasculitis Clinic between 1974 and 2004 were assessed. For
      inclusion, a renal biopsy showing predominant mesangial IgA immune deposits was
      required, plus at least two of: purpuric rash, arthralgia, abdominal pain.
      RESULTS: Ten patients (27%) progressed to end-stage renal failure (ESRF). Renal
      failure rates were highest in the first decade, with survival rate 72% at 5
      years, 68% at 10 years and 46% at final review. Risk factors for ESRF were:
      proteinuria > or =1 g/day during follow-up (RR 83.8, p = 0.0006); hypertension at
      presentation (RR = 53.3, p = 0.0045) and during follow-up (RR = 5.9, p = 0.05);
      renal impairment at presentation (RR 8.0, p = 0.0015); age <30 years (RR 7.6, p =
      0.02); and male sex (RR = 6.0, p = 0.05). Biopsies frequently showed crescents,
      mostly affecting <50% of glomeruli; their presence predicted ESRF, as did
      interstitial fibrosis and tubular atrophy. Renal remission, in contrast, was also
      high (43%). Cytotoxics were used in 32%, with no clear effect on outcome.
      Relapses affecting the classical extra-renal systems were common, but were not
      associated with declines in renal function. A high proportion of patients (41%)
      also suffered vasculitic organ injuries outside the classical systems.
      DISCUSSION: HSN in adults is a serious relapsing disease, causing renal failure
      as frequently as in small-vessel ANCA-positive vasculitides. Prognosis and risks
      differed in this series from those in other countries, including a higher risk of
      ESRF than in previous series. Distinct groups developed either ESRF, or remitted.
      The absence of clear benefit suggests that corticosteroids should be reserved for
      patients with serious disease, and that cytotoxics may not be merited for those
      at high risk of renal failure.

PMID- 16565524
TI  - Abolition of the tapetum suicide program ruins microsporogenesis.
AB  - Microsporogenesis in angiosperms takes places within the anther. Microspores are
      surrounded by a layer of cells, the tapetum, which degenerates during the later
      stages of pollen development with cytological features characteristic of
      programmed cell death (PCD). We report herein that the expression of AtBI-1,
      which suppresses Bax-induced cell death, in the tapetum at the tetrad stage
      inhibits tapetum degeneration and subsequently results in pollen abortion, while
      activation of AtBI-1 at the later stage does not. Our results demonstrate that
      the PCD signal commences at the tetrad stage and that the proper timing of PCD in
      the tapetum is essential for normal microsporogenesis.

PMID- 16565525
TI  - Successful outcomes with the h.e.a.l. program.
AB  - The successful treatment of acute and chronic wounds can be daunting. In an
      effort to improve client outcomes and manage spiraling nursing and dressing
      supply costs, the Community Care Access Centre of Wellington-Dufferin (Canada)
      implemented the Healing Excellence with Advanced Learning (h.e.a.l.) program in
      March 2003 as a standardized, evidence-based means of providing wound care to
      home care clients. While implementation challenges remain and education is
      ongoing, indepth wound management education and standardization of care have
      reduced the percentage of patients receiving nonevidence-based wound care and
      resultant frequent dressing changes. This has enabled the Centre to reallocate
      1.5 million dollars from dressing change costs to new nursing initiatives beyond
      wound care. The initial goals of the program were met. Continuing documentation
      of its outcomes will help underscore the importance of evidence-based protocols
      and provider education to the wound healing process.

PMID- 16565526
TI  - A case study of negative pressure wound therapy to manage acute necrotizing
      fasciitis.
AB  - Acute necrotizing fasciitis is a devastating infectious process that requires
      immediate surgical debridement. Intravenous antibiotic treatment, hyperbaric
      oxygen therapy, and wound management are considered the standard of care.
      Subsequent wound closure is achieved with split-thickness skin grafting, delayed
      surgical closure, or healing by secondary intention. When a patient refuses
      additional surgical treatment or is no longer a surgical candidate, as was the
      case with a patient who presented with acute necrotizing fasciitis caused by
      Clostridium perfringens in the upper extremity, secondary intention healing is
      the only treatment option. Following surgery and intravenous antibiotic
      treatment, her wounds were managed with topical negative pressure wound therapy.
      No adverse events occurred and the wounds were almost completely healed 63 weeks
      following surgery. Research to develop evidence-based protocols of care for the
      closure of these wounds is needed.

PMID- 16565527
TI  - Up close and personal with deep vein thrombosis.
AB  - Deep vein thrombosis - the formation of clots in one of the body's deep veins
      (usually in the lower extremities) - develops as a result of vascular damage to
      the vein wall, venous stasis, and hypercoagulability (Virchow's triad). Among the
      many problems it can cause, the condition can escalate the challenge of healing a
      chronic wound. If a patient presents with pain, swelling, warmth, muscle cramps,
      and/or redness, the clinician should consider deep vein thrombosis, even if the
      patient does not initially appear to be at risk. Because approximately 2 million
      Americans have deep vein thrombosis every year (including otherwise healthy
      adults, the elderly, and persons with and without a history of venous
      insufficiency), prompt attention to symptoms is warranted. Diagnosis takes into
      consideration risk factors such as hypercoagulability, estrogen contraception,
      and Factor V Leiden mutation and is confirmed via compression ultrasonography and
      duplex ultrasound. Management includes anticoagulation therapy and thrombolytic
      therapy; prevention focuses on avoiding long periods of sitting, wearing
      compression hose when necessary and, for persons at risk, prophylactic
      anticoagulant therapy. Prescribed bedrest as a result of deep vein thrombosis
      provided one clinician/patient who did not consider herself to be at risk the
      opportunity to explore the condition in depth.

PMID- 16565528
TI  - Let us not just work at the spinal level.

PMID- 16565529
TI  - Spine revisited: principles and parlance redefined.
AB  - A revised appreciation of the evolution and the nature of bone in general and of
      vertebrae in particular, allows revisiting the human spine to usher in some new
      principles and more rational parlance, that embody spine's phylogeny, ontogeny,
      anatomy and physiology. Such an approach accords primacy to spine's soft-tissues,
      and relegates to its bones a secondary place.

PMID- 16565530
TI  - Role of mechanical factors in the evaluation of pedicle screw type spinal
      fixation devices.
AB  - Prior to implantation, spinal implants are subjected to rigorous testing to
      ensure safety and efficacy. A full battery of tests for the devices may include
      many steps ranging from biocompatibility tests to in vivo animal studies. This
      paper describes some of the essential tests from a mechanical engineering
      perspective (e.g., motion, load sharing, bench type tests, and finite element
      model analyses). These protocols reflect the research experience of the past
      decade or so.

PMID- 16565531
TI  - Atlantoaxial fixation: overview of all techniques.
AB  - Over the past century, steady advances have been made in fixating an unstable
      atlantoaxial complex. Current options for fixation of the atlantoaxial complex
      include posterior clamps, posterior wiring techniques, C1-C2 transarticular screw
      fixation, posterior C1 lateral mass screw with C2 pars or pedicle screw fixation,
      and anterior transoral C1 lateral mass to C2 vertebral body fixation.

PMID- 16565532
TI  - Odontoid screw fixation for fresh and remote fractures.
AB  - Fractures of the odontoid process are common, accounting for 10% to 20% of all
      cervical spine fractures. Odontoid process fractures are classified into three
      types depending on the location of the fracture line. Various treatment options
      are available for each of these fracture types and include application of a
      cervical orthosis, direct anterior screw fixation, and posterior cervical fusion.
      If a patient requires surgical treatment of an odontoid process fracture, the
      timing of treatment may affect fusion rates, particularly if direct anterior
      odontoid screw fixation is selected as the treatment method. For example, type II
      odontoid fractures treated within the first 6 months of injury with direct
      anterior odontoid screw fixation have an 88% fusion rate, whereas fractures
      treated after 18 months have only a 25% fusion rate. In this review, we discuss
      the etiology, biomechanics, diagnosis, and treatment (including factors affecting
      fusion such as timing and fracture orientation) options available for odontoid
      process fractures.

PMID- 16565533
TI  - Anterior cervical plating.
AB  - Although anterior cervical instrumentation was initially used in cervical trauma,
      because of obvious benefits, indications for its use have been expanded over time
      to degenerative cases as well as tumor and infection of the cervical spine. Along
      with a threefold increase in incidence of cervical fusion surgery, implant
      designs have evolved over the last three decades. Observation of graft subsidence
      and phenomenon of stress shielding led to the development of the new generation
      dynamic anterior cervical plating systems. Anterior cervical plating does not
      conclusively improve clinical outcome of the patients, but certainly enhances the
      efficacy of autograft and allograft fusion and lessens the rate of
      pseudoarthrosis and kyphosis after multilevel discectomy and fusions. A review of
      biomechanics, surgical technique, indications, complications and results of
      various anterior cervical plating systems is presented here to enable clinicians
      to select the appropriate construct design.

PMID- 16565534
TI  - Indications and techniques for anterior cervical plating.
AB  - Anterior cervical plating is commonly performed to stabilize anterior cervical
      fusions. Modern plating options include dynamic plates, with screws that can
      either toggle within fixed holes or translate within slotted holes. Regardless of
      the plating system used, paramount to success and avoidance of complications with
      plated anterior cervical fusions are meticulous plating techniques, exacting
      graft carpentry, and understanding the biomechanical limitations of plating in
      certain situations, such as multilevel corpectomies reconstructed with a single
      strut graft. In order to prevent graft-related complications associated with long
      strut grafts, additional posterior fixation and fusion, or alternative corpectomy
      constructs, such as multilevel anterior cervical discectomy and fusion,
      corpectomy-discectomy, and corpectomy-corpectomy, should be considered instead if
      the pattern of stenosis allows.

PMID- 16565535
TI  - Artificial cervical disc replacement--an update.

PMID- 16565536
TI  - Artificial cervical disc replacement: principles, types and techniques.
AB  - Cervical arthroplasty after anterior decompression with insertion of a prosthetic
      total disc replacement has been suggested as an alternate to anterior cervical
      fusion. Currently there are four cervical arthroplasty devices available on the
      market whose results in clinical use have been reported. Each device varies in
      terms of materials, range of motion, insertion technique and constraint. It is
      not known which device is ideal. Early studies suggest that in the short term,
      the complication rate and efficacy is no worse than fusion surgery. Long-term
      results have not yet been reported. This review examines the current prostheses
      available on the market as well as discussing issues regarding indications and
      technique. Pitfalls are discussed and early experiences reviewed. In time, it is
      hoped that a refinement of cervical arthroplasty occurs in terms of both
      materials and design as well as in terms of indications and clinical outcomes as
      spinal surgeons enter a new era of the management of cervical spine disease.

PMID- 16565537
TI  - Kyphoplasty: chances and limits.
AB  - Kyphoplasty provides a minimal-invasive surgical technique for the cement
      augmentation of vertebral bodies following osteoprotic compression fractures or
      malignant processes. Kyphoplasty has been developed as an advancement of
      vertebroplasty. Both procedures feature high-success rates in terms of reliable
      and lasting reduction of pain. Advantages of kyphoplasty over vertebroplasty are
      to be seen in the possibility of deformity correction as well as in a decreased
      risk of cement leakage, which represents the most important source for clinical
      complications. Long-term experiences with the effect of cementing vertebral
      bodies are sparse. Thus indications and possibilities have to be judged
      realistically. Conditions, which have to be considered before performing
      kyphoplasty or vertebroplasty include age of the patient, age of the fracture,
      degree of deformation and additional degenerative changes of the spine. This
      article summarizes the present research and literature as well as indications and
      contraindications and is thought to provide guidelines for the aforementioned
      decision-making processes.

PMID- 16565538
TI  - Posterior thoracic segmental pedicle screw instrumentation: evolving methods of
      safe and effective placement.
AB  - The use of pedicle screw instrumentation in the spine has evolved over the last
      two decades. The initial use of pedicle screws began in the lumbar spine. As
      surgeons have become more comfortable with the complex anatomy required for
      accurate screw placement, the use of pedicle instrumentation has evolved to
      include their use in the thoracolumbar and thoracic spine. The impetus behind
      their increased use is a result of the many advantages that pedicle screw
      anchorage offers over traditional hook and rod constructs. Improved deformity
      correction and overall construct rigidity are two important advantages of pedicle
      screw instrumentation due its three-column control over the spinal elements.
      First, pedicle screw instrumentation obviates the need to place instrumentation
      within the spinal canal with its inherent risk of neurologic injury. Second, the
      placement of pedicle screws is independent of facet or laminar integrity and thus
      has been extremely useful in traumatic, neoplastic, and degenerative conditions.
      The benefits of pedicle screws in the thoracic spine has been tempered by the
      potential for catastrophic neurological or soft tissue injuries due to the close
      proximity of these structures. The narrow and inconsistent shape of the thoracic
      pedicles, especially in spinal deformity, makes their placement technically
      challenging. As a result, surgeons have employed a number of techniques to ensure
      the safe and efficacious placement of thoracic pedicle screws. Detailed anatomic
      landmarks used to determine pedicle location, intraoperative imaging including
      navigation, and neurophysiological monitoring are some of the techniques
      currently used by surgeons. The implementation of these techniques and a thorough
      understanding of the complex three-dimensional anatomy have allowed surgeons to
      successfully place thoracic and thoracolumbar pedicle screws.

PMID- 16565540
TI  - Percutaneous vertebroplasty: current concepts and local experience.
AB  - With the aging population in our country, symptomatic osteoporotic compression
      fractures are increasingly common. Osteolytic compression fractures from spinal
      metastasis are also becoming more frequently seen because of the longer life
      expectancy from improvements in chemotherapy. Percutaneous vertebroplasty with
      PMMA has been shown to be an efficient procedure to treat pain due to these
      fractures. It is a minimally invasive procedure performed under local anesthesia
      and sedation. Injection of PMMA provides immediate stability when it hardens, and
      permits the patient to ambulate without pain. Appropriate patient selection is
      the key to clinical success. However, this procedure must be treated with
      respect, and has to be performed by physicians with the necessary training.
      Otherwise, increased pain, paralysis, and even death may occur from this
      seemingly innocuous procedure. In this article, I will deal with the background
      issues of osteoporotic and osteolytic vertebral compression fractures, patient
      selection, surgical technique, complications, and review of current literature on
      vertebroplasty. Key areas of development in this field include the use of
      kyphoplasty, defining the role of prophylactic augmentation, and improvements in
      biomaterials.

PMID- 16565539
TI  - Dynamic stabilization devices in the treatment of low back pain.
AB  - Soft stabilization has an important role in the treatment of the degenerative
      lumbar spine. Fusion of one or two motion segments may not make a big difference
      in the total range of motion of the lumbar spine, but preserving flexibility of a
      motion segment may prevent adjacent segment disease and may permit disc
      replacement, even when facet joints need to be excised. A favourable environment
      is created in the motion segment by unloading the disc and permitting near normal
      motion, the disc may be able to repair itself or may supplement reparative
      potential of gene therapy.

PMID- 16565541
TI  - Spinopelvic fixation.

PMID- 16565543
TI  - Prosthetic lumbar disc replacement for degenerative disc disease.
AB  - Mechanical articulated device to replace intervertebral disc as a treatment for
      low back pain secondary to disc degeneration has emerged as a promising tool for
      selected patients. The potential advantages are prevention of adjacent segment
      degeneration, maintenance of mobility as well as avoidance of all the
      complications associated with fusion. The short-term results have been comparable
      to that of fusion, a few mid-term results have shown mixed outcome, but
      information on long-term results and performance are not available at present.
      The rationale for lumbar disc arthroplasty, indications, contraindications, the
      various artificial devices in the market and the concepts intrinsic to each of
      them, basic technique of insertion, complications are discussed and a brief
      summary of our experience with one of the devices is presented.

PMID- 16565542
TI  - Video assisted thoracoscopic surgery for spinal conditions.
AB  - Video-assisted thoracoscopic surgery (VATS) has become an alternative treatment
      tool for a variety of spinal conditions in the last two decades. This endoscopic
      or "keyhole" approach minimizes the chest wall morbidity related to the
      traditional thoracotomy. The current indications for VATS are the same as in any
      open anterior spinal surgery. This article reviews the outcomes of VATS
      treatments in thoracic disc diseases, fractures, tumors and vertebral
      osteomyelitis. In addition, we have described our "learning curve" and surgical
      techniques using video-assisted thoracoscopic spinal releases and instrumentation
      in the treatment of 50 patients with adolescent idiopathic scoliosis.

PMID- 16565544
TI  - Surgical management of spondylolisthesis overview of literature.

PMID- 16565545
TI  - Thoracic pedicle screw placement: free-hand technique.

PMID- 16565546
TI  - Translaminar facetal screw (Magerl's) fixation.
AB  - Translaminar facet screw fixation (TLFS) achieves stabilization of the vertebral
      motion segment by screws inserted at the base of the spinous process, through the
      opposite lamina, traversing the facet joint, and ending in the base of the
      transverse process. It is simple, does not require any specialized equipment, and
      has the advantages of being a procedure of lesser magnitude, lesser operative
      time, less cost and few complication rate. Recently there is growing interest in
      this technique to augment the anterior lumbar fusions to achieve global fusion
      less invasively. In this review article, we discuss the clinical and
      biomechanical considerations, surgical technique, indications, contraindications
      and recent developments of TLFS fixation in lumbar spine fusion.

PMID- 16565547
TI  - Techniques in the treatment of craniovertebral instability.
AB  - The techniques of craniovertebral region stabilization introduced and used by the
      senior author over the last 20 years are summarized. The lateral masses of atlas
      and axis are strong and largely cancellous in nature and can be used for direct
      implantation of screws. Opening up of the joint and placement of bone graft
      within the joint stabilizes the region and provides a large area for bone fusion.
      Distraction of the facets provides an opportunity to treat a range of congenital
      craniovertebral anomalies. The technique of exposure of the lateral mass of the
      atlas and axis and the atlantoaxial joint is technically relatively complex and
      needs precise understanding of anatomy of the vertebral artery and training with
      cadavers.

PMID- 16565548
TI  - Decision making in thoracolumbar fractures.

PMID- 16565549
TI  - Outcomes of patients with stable low-risk coronary artery disease receiving
      medical- and PCI-preceding therapies in Japan: J-SAP study 1-1.
AB  - BACKGROUND: Stable coronary artery disease (CAD) is classified into 2 types: high
      risk (ie, 3-vessel disease, left main trunk lesions, or ostial lesions of the
      left anterior descending (LAD)) and low-risk (1- or 2-vessel disease other than
      ostial lesions of the LAD), which comprise the majority of CAD patients.
      According to ACC/AHA/ACP-ASIM guidelines for low-risk CAD, anti-anginal agents
      should be initially administered to control attacks, then coronary intervention
      should be considered when medical therapy is not effective (medical-preceding
      therapy: M). In Japan, however, the initial treatment is generally percutaneous
      coronary intervention (PCI) combined with medical therapy (PCI-preceding therapy:
      P). METHODS AND RESULTS: In the present study the long-term outcomes of 190 M
      patients and 192 matched P patients at 34 nationwide hospitals were surveyed over
      3 years (mean: 3.4 years) starting in 2000. Age, gender, initial severity of
      anginal symptoms, number of lesion vessels, risk factors and prescriptions were
      similar between the 2 groups. During the 3.4-year follow-up, additional PCI or
      coronary artery bypass grafting was required in 9.4% of the M group and in 33.2%
      of the P group. The rates of cardiac death were similar (1.6% in M and 2.6% in
      P). The overall rate of cardiac death and acute coronary syndrome was 2.1% in M
      and 4.7% in P, but the difference was not significant. The grade of anginal
      symptoms 12 months later was well improved in both M (1.6+/-1.4 to 0.6+/-0.9) and
      P (1.7+/-1.4 to 0.3+/-0.7) and there was no significant difference. Averaged
      annual medical cost was lower in M than in P (4.4-fold lower in the first year
      and 3.1-fold by the next year). CONCLUSIONS: The present study suggests that M
      and P for Japanese low-risk CAD may have a similar effect on long-term prognosis,
      but M is cheaper.

PMID- 16565550
TI  - Effect of conventional risk factors for excess cardiovascular death in men:
      NIPPON DATA80.
AB  - BACKGROUND: The present study examined how sex differences in conventional risk
      factors for cardiovascular disease (CVD), especially smoking, account for excess
      male mortality from CVD in Japan. METHODS AND RESULTS: In a 14-year follow-up
      study, causes of death were ascertained among 10,546 Japanese aged 30 years or
      older at the baseline. The proportion of the excess male risk of CVD explained by
      the differences in risk factors was estimated as (HR0-HR1)/(HR0-1), where HR0 is
      the age-adjusted hazard ratio (men vs women) and HR1 is the age and risk factor
      adjusted hazard ratio. The age-adjusted male:female ratios were 1.60 (95%
      confidence interval (CI), 1.32-1.94) for CVD, 1.75 (95% CI, 1.33-2.30) for
      stroke, and 1.55 (95% CI, 0.97-2.49) for coronary heart disease. The proportion
      of excess male risk of CVD explained by smoking was 46% and excess risk explained
      by all risk factors including smoking was 36%. In men, drinking habits decreased
      the excess risk of CVD. Except for the association between drinking habits and
      CVD, the impact of the hazard ratios of conventional risk factors had no sex
      difference. CONCLUSIONS: Smoking contributes substantially to excess male
      mortality from CVD when the smoking rates vary substantially by sex.

PMID- 16565552
TI  - The optimal cut-off point of C-reactive protein as an optional component of
      metabolic syndrome in Japan.
AB  - BACKGROUND: C-reactive protein (CRP) independently predicts cardiovascular
      disease (CVD) and is considered to be part of metabolic syndrome (MS). The
      concentration of CRP are proposed to be <1.0 mg/L as low risk, 1.0 to 3.0 mg/L as
      intermediate risk, and >3.0 mg/L as high risk for CVD in Western society. METHODS
      AND RESULTS: Apparently healthy 179 men and 166 women were categorized with
      modified National Cholesterol Education Program Adult Treatment Panel III
      criteria (body mass index > or = 25 in place of abdominal obesity) for defining
      MS. The cut-off points of CRP were evaluated for both MS defined by impaired
      fasting glucose criteria of > or = 110 mg/dl (MS110) and > or = 100 mg/dl
      (MS100), separately by sex. The optimal cut-off point of CRP was 0.65 mg/L in all
      subgroups. The sensitivity and specificity of this CRP value for male MS100,
      female MS100, male MS110, and female MS110 were 0.650 and 0.626, 1.000 and 0.771,
      0.739 and 0.609, and 1.000 and 0.756, respectively. CONCLUSIONS: The optimal cut
      off point of CRP for MS might be 0.65 mg/L in Japan and this value can be useful
      in routine clinical practice and studies on MS.

PMID- 16565551
TI  - Long-term prognosis of dilated cardiomyopathy revisited: an improvement in
      survival over the past 20 years.
AB  - BACKGROUND: Because of their favorable prognostic effects, angiotensin converting
      enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) and beta
      blockers have become background therapy in dilated cardiomyopathy (DCM). However,
      there are few reports concerning the long-term prognosis of Japanese patients
      with DCM in relation to these treatments. METHODS AND RESULTS: One hundred and
      fifty patients with DCM were divided into 2 groups: group A (n=46) (diagnosis:
      1982-1989) and group B (n=104) (diagnosis: 1990-2002). During follow-up period of
      6.9+/-4.8 years, 62 patients died and 1 patient had a heart transplant. The
      survival rate at 5 and 10 years was 60.9% and 34.8%, respectively, in group A
      patients, and 80.9% and 65.3%, respectively, in group B patients (p=0.0079). In
      group A patients, ACEI/ARB or beta blockers were less frequently used (p<0.0001),
      whereas antiarrhythmics (class Ia or Ib) were more often used (p<0.0001). The
      patients treated with ACEI/ARB and beta blockers showed a better survival rate
      than those without (p<0.0001). The patients with antiarrhythmics showed a worse
      survival rate than those without (p<0.0001). CONCLUSION: The prognosis of
      Japanese patients with DCM has significantly improved over the past 20 years.
      This improvement may be explained partly through the increased use of ACEI/ARB
      and beta blockers and a declining use of antiarrhythmics.

PMID- 16565553
TI  - Risk analysis for depression and patient prognosis after open heart surgery.
AB  - BACKGROUND: The aim of the present study was to determine the predictors of
      depression as a complication after open heart surgery and influence of depression
      on the patients' prognosis. METHODS AND RESULTS: During the last 3 years, 97
      patients (21.5%) of the 452 adult patients who had open heart surgery at our
      institute experienced depression after the operation. Patients who scored over 16
      points using a Center for Epidemiological Studies Depression Scale were diagnosed
      with significant symptoms of depression. Depressed patients (group I, n=97) and
      non-depressed patients (group II, n=355) in terms of mortality and length of
      hospital stay were compared. Predictors for depression were identified by
      logistic regression analysis. The postoperative hospital stay was significantly
      longer in group I. Hospital mortality was also significantly higher in group I.
      Female gender (odds ratio (OR): 5.15, p<0.0001), emergency surgery (OR: 4.46,
      p<0.0001), and being over 70 years of age (OR: 4.67, p<0.0001) were found to be
      significant predictors for postoperative depression. CONCLUSION: The prognosis
      for patients who had depression developed after open heart surgery was poor. It
      might be important to start prophylactic medication as soon as possible after the
      operation, particularly for patients at risk of having depression.

PMID- 16565554
TI  - Predominance of small dense low-density lipoproteins and abnormal glucose
      regulation in patients with acute coronary syndrome.
AB  - BACKGROUND: Although small dense low-density lipoprotein (sd-LDL) has an
      established association with diabetic dyslipidemia, previous studies have failed
      to show an association between sd-LDL and diabetes among coronary heart disease
      patients. This study investigated the prevalence of sd-LDL and abnormal glucose
      regulation in acute coronary syndrome (ACS). METHODS AND RESULTS: LDL size at the
      onset of ACS was measured by nondenatured gradient gel electrophoresis in 314 of
      429 consecutive patients. Sd-LDL was prevalent in 54% of the patients,
      irrespective of the presence of previously known diabetes (50% vs 60% in
      nondiabetes and diabetes, respectively). Diabetes was present in 122 (28%) of the
      patients, and 110 patients without diabetes underwent an oral glucose tolerance
      test. Impaired glucose tolerance (IGT) and newly detected diabetes were found in
      as many as 44% and 22% of the patients tested, even though their hemoglobinA1c
      levels were in the normal range (5.3+/-0.5%). The prevalence of sd-LDL was
      significantly higher in patients with glucose intolerance than in those with
      normal glucose tolerance (61% vs 42%). CONCLUSION: IGT and diabetes were far more
      common than normal glucose regulation in ACS patients, and the abnormal
      glycometabolism was closely associated with highly atherogenic sd-LDL.

PMID- 16565555
TI  - Vasodilatory effect of subsequent administration of fasudil, a rho-kinase
      inhibitor, surpasses that of nitroglycerin at the concentric coronary stenosis in
      patients with stable angina pectoris.
AB  - BACKGROUND: Recent studies have suggested that the Rho/Rho-kinase mediated
      pathway (Rho-kinase pathway) regulates the vasomotion of arteries in pathological
      conditions. However, it remains unclear regarding whether this pathway regulates
      the coronary vasomotion of atherosclerotic lesions. METHODS AND RESULTS: The
      coronary diameter at the concentric stenotic site, which is considered to reflect
      the whole circumferential atherosclerosis, in patients with stable angina
      pectoris (SAP; n=11) and the control site in patients with SAP and chest pain
      syndrome (CPS; n=9), was measured at baseline and after the intracoronary
      administration of nitroglycerin (200 microg) and the subsequent intravenous
      infusion of fasudil (30 mg for 30 min), a Rho-kinase inhibitor, during coronary
      angiography. The change in the diameter with fasudil at the concentric stenotic
      site (22.0+/-10.0%) was significantly higher than that with nitroglycerin (4.7+/
      6.0%, p<0.001) in patients with SAP. Meanwhile, the vasodilatory effect of
      nitroglycerin and fasudil at the control site was similar in both group of
      patients (25.5+/-17.3% and 21.9+/-14.9% in SAP and 34.4+/-20.8% and 33.2+/-23.6%
      in CPS, respectively). CONCLUSIONS: The vasodilatory effect of the subsequent
      administration of fasudil surpassed that of nitroglycerin at the concentric
      coronary stenosis in patients with SAP, thus suggesting that the Rho-kinase
      pathway regulates the coronary vasomotion of atherosclerotic lesions.

PMID- 16565556
TI  - Coronary artery spasm and the polymorphisms of the endothelial nitric oxide
      synthase gene.
AB  - BACKGROUND: Coronary artery spasm plays an important role in the pathogenesis of
      vasospastic angina, and contributes to the development of several acute coronary
      syndromes. Endothelial nitric oxide synthase (ecNOS) catalyzes the synthesis of
      nitric oxide, which regulates vascular tone, and may be related to coronary
      vasospasm. The present study investigated whether coronary spasm is related to
      particular polymorphisms of the ecNOS gene. METHODS AND RESULTS: Spasm
      provocation by serial infusions of acetylcholine was performed on 165 patients
      who were clinically suspected of having angina. In both study patients and
      healthy controls (n=400), genomic polymorphisms of the ecNOS gene were determined
      by using polymerase chain reaction. Quantitative luminal diameter measurements of
      the 3 major coronary arteries were initially obtained before and after
      acetylcholine injection, and then after isosorbide dinitrate injection, by using
      a computer-assisted analysis system. Logistic multiple regression analysis
      identified the a/a or a/b genotype in intron 4 of ecNOS (NOS4a: p=0.0431, odds
      ratio (OR) 2.43) and diabetes mellitus (p=0.0060, OR 4.88) as significant
      predictors of coronary spasm. In the patients with NOS4a, both the induced and
      spontaneous contractions were augmented. CONCLUSION: The present study results
      indicated that NOS4a could be a good marker for coronary artery spasm.

PMID- 16565557
TI  - Decrease in plasma adiponectin concentrations in patients with variant angina
      pectoris.
AB  - BACKGROUND: Plasma adiponectin is decreased in patients with coronary artery
      diseases, especially in patients with acute coronary syndrome (ACS). However, the
      correlation between plasma adiponectin and variant angina pectoris (VAP) has not
      been verified. Plasma adiponectin concentrations between VAP and other coronary
      artery diseases was compared in the present study. The association between plasma
      adiponectin concentration and VAP was also investigated. METHODS AND RESULTS:
      Plasma adiponectin concentrations in the VAP group (n=101) were compared with
      those of the ACS group (n=117), the stable angina pectoris group (n=108), and the
      normal coronary group (n=81). Plasma adiponectin concentrations in VAP and ACS
      were significantly lower than that of the normal coronary group (6.6+/-5.4 vs
      5.2+/-4.0 vs 9.0 +/-6.2 microg/ml, p<0.001, respectively). Multivariate analysis
      indicated that plasma adiponectin (odds ratio (OR) 0.735, 95% confidence interval
      (CI) 0.621-0.855, p=0.011), smoking (OR 2.012, 95% CI 1.210-3.880, p=0.020), and
      age (OR 0.976, 95% CI 0.957-0.997, p=0.022) correlated independently with the
      development of VAP. CONCLUSIONS: Our results suggest that a decrease in plasma
      adiponectin concentration might be associated with the development of VAP.

PMID- 16565558
TI  - Early positive biomarker in relation to myocardial necrosis and impaired fatty
      acid metabolism in patients presenting with acute chest pain at an emergency
      room.
AB  - BACKGROUND: Measurement of circulating biomarkers has enabled early diagnosis and
      risk assessment of acute coronary syndrome. This study sought diagnostic values
      of the first single-point data of biomarkers obtained soon after patient arrival
      by comparing with scintigraphically quantified myocardial injury in patients
      presenting with acute chest pain at an emergency room. METHODS AND RESULTS:
      Serial blood samples were taken soon after arrival in an emergency department in
      74 patients with suspected acute coronary syndrome to quantify blood levels of
      troponin-T (TnT), heart-type fatty acid-binding protein (H-FABP), myocardial
      bound creatine kinase (CK-MB), and myoglobin. Myocardial perfusion and metabolic
      defects were scintigraphically quantified. The first single-point data had high
      positive predictive values for detecting the defects (80-100%) but low negative
      predictive values (15-41%). CK-MB and TnT had higher specificities (73-100%) but
      significantly lower positive rates (22-27%) than the others (61-68%), resulting
      in greater sensitivities of H-FABP and myoglobin (75-80%) than those of CK-MB and
      TnT (29-35%). Among biomarkers, TnT peak concentrations most closely correlated
      with scintigraphic abnormalities. CONCLUSION: H-FABP can contribute to early
      detection of myocardial injury and TnT is most likely to correlate with injured
      myocardial mass. The differential features of biomarkers are complementary in
      patients with acute chest pain presenting at an emergency room.

PMID- 16565559
TI  - Close association of regional interleukin-6 levels in the infarct-related culprit
      coronary artery with restenosis in acute myocardial infarction.
AB  - BACKGROUND: The involvement of interleukin (IL)-6 in restenosis of the
      recanalized coronary artery after the percutaneous coronary intervention (PCI)
      was examined. METHODS AND RESULTS: There were 40 patients enrolled in the study
      who had acute myocardial infarction and whose infarct-related coronary arteries
      were treated by new thrombectomy devices and stenting. Blood samples were
      collected from the culprit coronary artery before and immediately after the
      maneuver of the PCI. Restenosis was defined as residual stenosis because it
      accounted for more than 50% at the follow-up coronary angiography. Plasma IL-6
      levels in the infarct-related coronary artery were 12.8 and 13.2 pg/ml before and
      after the initial maneuver of the PCI, respectively, values that were
      significantly greater than that of 7.2 pg/ml in the peripheral vein (p<0.0001).
      The levels of IL-6 in the pre- and the post-stage of PCI were significantly
      greater in the patients with restenosis than those without restenosis. The plasma
      IL-6 levels in the post-stage of PCI had significant correlations with late loss
      and loss index. CONCLUSIONS: The present study findings indicate that plasma IL-6
      levels in the culprit coronary artery at the post-stage of PCI are closely
      associated with the future restenosis of the revasculized coronary artery in
      acute myocardial infarction.

PMID- 16565560
TI  - Effect of granulocyte colony-stimulating factor treatment at a low dose but for a
      long duration in patients with coronary heart disease.
AB  - BACKGROUND: In animal models, granulocyte colony-stimulating factor (G-CSF)
      improves post-infarct cardiac function. However, in pilot studies involving
      patients with angina and acute myocardial infarction (AMI), G-CSF at a high dose
      frequently induced coronary occlusion or restenosis, but those at a low dose
      showed no significant beneficial effect. We hypothesized that a low dose but long
      duration of G-CSF will have a beneficial effect without serious complications to
      patients with coronary heart disease. METHODS AND RESULTS: Forty-six patients
      with angina or AMI were randomly assigned into G-CSF and non-G-CSF control
      groups, respectively. Recombinant G-CSF was subcutaneously injected once a day
      for 10 days. The leukocyte counts in the peripheral blood were controlled at
      approximately 30,000/microl. One month later, a Thallium-201 single photon
      emission computed tomography revealed the increased percentage uptake and the
      reduced extent and severity scores in the G-CSF angina group. In the G-CSF AMI
      group, the curve between the ejection fraction and peak creatine kinase shifted
      significantly upward, compared with that of the non-G-CSF AMI group. Serious
      complications were not observed during the 6 months of observation. CONCLUSIONS:
      A low dose but long duration of G-CSF treatment may have a beneficial effect
      without any serious complications in patients with coronary heart disease.

PMID- 16565561
TI  - Risk factors of atrial fibrillation following coronary artery bypass grafting: a
      preliminary report.
AB  - BACKGROUND: To evaluate the risks factors of atrial fibrillation (AF) following
      coronary artery bypass grafting (CABG). METHODS AND RESULTS: Twelve hundred
      patients subjected to CABG were included. Postoperative AF developed in 278
      patients (23.2%). Statistical analysis identified 5 independent predictors of AF:
      advanced age, history of supraventricular arrhythmias, preoperative heart
      failure, operation with standard CABG technique and repeated revascularization.
      CONCLUSIONS: Postoperative AF caused a significant increase in mortality and
      hospitalization length. There were 4 independent risk factors of postoperative
      AF. Administration of beta-blockers and the OPCAB (off-pump CABG) operating
      technique were identified as protective factors.

PMID- 16565562
TI  - Comparison of nifekalant and lidocaine for the treatment of shock-refractory
      ventricular fibrillation.
AB  - BACKGROUND: Although nifekalant is a class III antiarrhythmic agent without
      negative inotropic activity, its effect in patients with shock-refractory
      ventricular fibrillation remains unclear. METHODS AND RESULTS: Patients who had
      an out-of-hospital cardiac arrest with ventricular fibrillation that persisted
      after 3 shocks from an external defibrillator, intravenous epinephrine, and
      another shock were retrospectively studied. The patients received lidocaine from
      January 1997 through June 2001 and nifekalant from July 2001 through December
      2004. Short-term survival rates (survival to hospital admission and 24-h
      survival) were compared between the groups. The study group comprised 120
      patients (mean age: 62+/-16 years): 55 received nifekalant and 65 received
      lidocaine. Age, sex, history of ischemic heart disease, whether arrest was
      witnessed or not and time to arrival at the hospital did not differ significantly
      between the groups. As compared with lidocaine, nifekalant was associated with
      significantly higher rates of survival to hospital admission (67% vs 37%,
      p<0.001) and 24-h survival (53% vs 31%, p=0.01). Multivariate analysis showed
      that treatment with nifekalant and early initiation of cardiopulmonary
      resuscitation were independent predictors of 24-h survival. CONCLUSIONS: As
      compared with lidocaine, nifekalant may improve short-term survival in patients
      with out-of-hospital cardiac arrest due to shock-refractory ventricular
      fibrillation.

PMID- 16565563
TI  - Time course and prognostic value of plasma levels of N-terminal pro-brain
      natriuretic peptide in patients after ischemic stroke.
AB  - BACKGROUND: The association between plasma levels of N-terminal pro-brain
      natriuretic peptide (NT-proBNP) and prognostic outcomes in patients after
      ischemic stroke remains unknown. The present study tested the hypothesis that NT
      proBNP level is noticeably increased after ischemic stroke and that elevated NT
      proBNP is associated with unfavorable clinical outcomes (UFCO). METHODS AND
      RESULTS: Blood samples for NT-proBNP levels were collected serially and examined
      with sandwich immunoassay after acute ischemic stroke in 86 consecutive patients.
      The NT-proBNP levels were also measured in 30 healthy control volunteers and 30
      at-risk control subjects. The NT-proBNP levels were significantly higher at 4
      intervals after ischemic stroke than in healthy and at-risk control subjects (all
      p<0.001). The NT-proBNP decreased to a significantly lower level on day 21 and to
      a substantially lower level on day 90. Additionally, the NT-proBNP level at any
      of the 4 intervals was significantly higher in patients with than in patients
      without UFCO (defined as combined congestive heart failure > or = class 3, acute
      myocardial infarction, recurrent stroke or any cause of death) (all p<0.01).
      Multivariate analysis demonstrated that age and NIH Stroke Scale were the 2
      strongest independent predictors of increased NT-proBNP levels (all p<0.01).
      Furthermore, increased NT-proBNP (> or = 150 pg/ml) was the strongest independent
      predictor of long-term (mean follow-up: 24 months) UFCO (26 patients) (all
      p<0.05). CONCLUSIONS: The NT-proBNP level was markedly elevated after acute
      ischemic stroke and declined substantially thereafter. An increased NT-proBNP
      level was strongly and independently correlated with UFCO in patients after
      ischemic stroke.

PMID- 16565564
TI  - Pharmacoeconomic analysis of cilostazol for the secondary prevention of cerebral
      infarction.
AB  - BACKGROUND: The antiplatelet agent, cilostazol, is known to reduce the risk of
      subsequent cerebral infarction. However, the cost effectiveness of such treatment
      in comparison to aspirin has not been studied. METHODS AND RESULTS: A Markov
      model was developed to calculate the health outcomes and associated costs for 65
      year-old patients with cerebral infarction who were treated with 200 mg/day
      cilostazol or 81 mg/day aspirin. Cilostazol was more effective, but also more
      expensive than aspirin. Cilostazol would extend quality-adjusted life years
      (QALY) by 0.64, while increasing life-time costs by approximately Yen 1.1
      million. The incremental cost-effectiveness ratio of cilostazol in comparison
      with aspirin was estimated to be Yen 1.8 million per QALY. CONCLUSIONS: The use
      of cilostazol to prevent recurrence of cerebral infarction appears to be cost
      effective.

PMID- 16565565
TI  - Non-invasive assessment of coronary arterial tone using trans-thoracic Doppler
      echocardiography.
AB  - BACKGROUND: As coronary flow velocity (CFV) is inversely related to the luminal
      size that exists for the myocardial bed, the elevated arterial tone can be
      assessed as the higher flow velocity in the epicardial artery. We examined the
      usefulness of transthoracic Doppler echocardiography (TTDE) for the assessment of
      coronary arterial tone. METHODS AND RESULTS: A total of 32 patients underwent
      TTDE and angiography. The luminal diameter (LD) in the left anterior descending
      artery (LAD) was measured by using quantitative coronary angiography before and
      after nitroglycerin (NTG) administration. The ratio of post NTG LD to the control
      (LD(NTG/Pre)) was assessed as a standard parameter of coronary arterial tone. We
      also measured CFV and CFV reserve (CFVR) at the LAD by TTDE. We evaluated the
      change of CFV (CFV(NTG/Pre)) and CFVR (CFVR(NTG/Pre)) following NTG
      administration. The LD increased from 1.98+/-0.46 to 2.51+/-0.34 mm (p<0.001),
      while the CFV decreased from 23.9+/-10.0 to 16.3+/-5.6 cm/s (p<0.03), and the
      CFVR increased from 2.39+/-0.65 to 3.56+/-1.12 (p<0.001). There were significant
      correlations between CFV(NTG/Pre) and LD(NTG/Pre) (p<0.0001, R2 = 0.532), and
      between the CFVR(NTG/Pre) and LD(NTG/Pre) (p<0.0001, R2 = 0.715). CONCLUSION:
      TTDE can assess the coronary arterial tone by measuring the responses of CFV and
      CFVR to NTG administration.

PMID- 16565566
TI  - Repeated thermal therapy up-regulates endothelial nitric oxide synthase and
      augments angiogenesis in a mouse model of hindlimb ischemia.
AB  - BACKGROUND: Nitric oxide (NO), constitutively produced by endothelial NO synthase
      (eNOS), plays roles in angiogenesis. Having reported that thermal therapy up
      regulated the expression of arterial eNOS in hamsters, we investigated whether
      this therapy increased angiogenesis in mice with hindlimb ischemia. METHODS AND
      RESULTS: Unilateral hindlimb ischemia was induced in apolipoprotein E-deficient
      mice, which were divided into control and thermal therapy groups. The latter mice
      were placed in a far-infrared dry sauna at 41 degrees C for 15 min and then at 34
      degrees C for 20 min once daily for 5 weeks. Laser Doppler perfusion imaging
      demonstrated that the ischemic limb/normal side blood perfusion ratio in the
      thermal therapy group was significantly increased beyond that in controls (0.79+/
      0.04 vs 0.54+/-0.08, p<0.001). Significantly greater capillary density was seen
      in thermal therapy group (757+/-123 /mm2 vs 416+/-20 /mm2, p<0.01). Western
      blotting showed thermal therapy markedly increased hindlimb eNOS expression. To
      study possible involvement of eNOS in thermally induced angiogenesis, thermal
      therapy was given to mice with hindlimb ischemia with or without N(G)-nitro-L
      arginine methyl ester (L-NAME) administration for 5 weeks. L-NAME treatment
      eliminated angiogenesis induced using thermal therapy. Thermal therapy did not
      increase angiogenesis in eNOS-deficient mice. CONCLUSION: Angiogenesis was
      induced via eNOS using thermal therapy in mice with hindlimb ischemia.

PMID- 16565567
TI  - Effects of intramyocardial administration of slow-release basic fibroblast growth
      factor on angiogenesis and ventricular remodeling in a rat infarct model.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) stimulates neoangiogenesis.
      Incorporation into biodegradable gelatin hydrogels provides the sustained release
      of bFGF. The effects of intramyocardial injections of slow-release bFGF on
      neoangiogenesis in a rat model of infarction were investigated. METHODS AND
      RESULTS: Myocardial infarction was induced in rats using coronary artery
      ligation. A total of 124 rats received an intramyocardial injection of 20 microg
      of bFGF, the same amount of bFGF incorporated into gelatin hydrogel (bFGF + gel),
      gelatin hydrogel (gel) or saline. Ventricular function was evaluated by
      echocardiography 2 or 4 weeks later. Morphometric and histological analyses were
      used to evaluate infarct size, vascular density and myocardial apoptosis.
      Capillary density in the infarct border zone was higher in the bFGF and bFGF +
      gel groups than in the saline and gel groups at 4 weeks (p<0.001). Arteriolar
      density was higher in the bFGF + gel group than in the other 3 groups (p<0.05).
      The bFGF and bFGF + gel groups contained fewer apoptotic cardiomyocytes in the
      border zone than the saline and gel groups (p<0.01). The bFGF+gel group had
      thicker (p<0.05) and less expanded infarcts (p<0.01) compared with the saline
      group at 4 weeks. CONCLUSIONS: Incorporation of bFGF in gelatin hydrogels
      enhanced the effects of bFGF on arteriogenesis, ventricular remodeling and
      cardiac function.

PMID- 16565568
TI  - Changes in coronary resistance related to the stages of the female life cycle.
AB  - BACKGROUND: Estrogen is known to dilate the coronary vascular system mainly
      through nitric oxide (NO) release. However, it has not been determined whether or
      not this effect occurs equally throughout all stages of the female life cycle. We
      examined the changes in coronary flow properties in adolescent, adult and
      ovariectomized (OVX) female rats using the endothelial NO synthetase blocker, L-N
      (omega) nitroarginine (L-NNA). METHODS AND RESULTS: Female rats were divided into
      3 groups: adolescent (13 weeks, n=6), adult (19 weeks, n=8) and OVX (20 weeks,
      n=7, 12 weeks after oophorectomy). Coronary effluent was measured using the
      Langendorff non-working heart model before and 15 min after the use of L-NNA. In
      OVX rats, coronary effluent was significantly decreased in comparison with
      adolescent and adult rats (adolescent vs OVX: p<0.001; adult vs OVX: p<0.05).
      After treatment with L-NNA, coronary effluent was significantly higher in the
      adolescent group compared with the adult and OVX groups (adolescent vs adult:
      p<0.01; adolescent vs OVX: p<0.0005). CONCLUSIONS: Oophorectomy brought about an
      increase in coronary vascular resistance. L-NNA exacerbated coronary vascular
      resistance in relation to maturation. It is suggested that the effect of estrogen
      on vascular dilatation in adolescents is largely dependent on a non-NO pathway,
      whereas adults are largely dependent on an NO pathway.

PMID- 16565569
TI  - Angiotensin II receptor antagonist attenuates expression of aging markers in
      diabetic mouse heart.
AB  - BACKGROUND: Diabetes mellitus is an independent risk factor for heart failure.
      Diabetes mellitus causes other age-related cardiovascular diseases. We assessed
      the hypothesis that hearts from diabetic animals are associated with accelerated
      aging processes. We also examined the effect of an angiotensin II receptor
      blocker (ARB) on the expression of senescence-associated molecules. METHODS AND
      RESULTS: We administered an ARB (candesartan 10 mg/kg per day) or saline to
      diabetic db/db or control db/+ mice. The treatment was started when mice were 10
      weeks-old, and continued for 15 weeks. Systolic function was impaired in db/db
      mice and candesartan improved cardiac function. The amount of phosphorylated Akt
      and S6 was decreased in saline-treated db/db mice, and candesartan treatment
      partially preserved phosphorylation. The amount of p21, p27, p53 or Rb was
      increased in the heart tissue of saline treated db/db mice. Candesartan treatment
      completely suppressed the increases of p21, p27, p53 and Rb. CONCLUSIONS: An ARB
      improved cardiac function of diabetic animals, and this was accompanied by
      decreases of senescence-associated molecules in the myocardium. ARB may be a
      modality for heart failure patients with diabetes mellitus.

PMID- 16565570
TI  - Cross-bridge-dependent change in Ca2+ sensitivity is involved in the negative
      inotropic effect of nifedipine in aequorin-injected ferret ventricular muscles.
AB  - BACKGROUND: We hypothesized that the negative inotropic effect of nifedipine
      (Nif) on cardiac ventricular muscle is partly due to the cross-bridge-dependent
      decrease of Ca2+ sensitivity of the myofilaments as well as the decrease in Ca2+
      influx. METHOD AND RESULTS: We used aequorin-injected ferret papillary muscles
      and measured the slope of the extra-Ca(2+)-tension relation which expresses the
      change in the Ca2+ sensitivity through the feedback from the cross-bridges.
      Twitch tension was decreased significantly by 0.5 micromol/L Nif accompanying a
      significant reduction of the Ca2+ transient peak. When Nif (0.2-0.5 micromol/L)
      was added to the solution with 8 mmol/L Ca2+, the slope of the extra-Ca2+-tension
      relation became steeper in a concentration-dependent manner, which was similar to
      the change in the slope when the concentration of Ca2+ was decreased from 8 to 1
      mmol/L in the absence of Nif. BAY-K 8644 (0.3 micromol/L), a dihydropyridine
      receptor agonist, showed the opposite effect on the slope of the extra-Ca2+
      tension relation to that observed in Nif. However, 2,3-butanedione monoxime (3
      mmol/L), an inhibitor of the active cross-bridges, antagonized the effect of BAY
      K 8644. CONCLUSION: Nif exerts its negative inotropic effect on cardiac muscle by
      suppressing Ca2+ binding to troponin C via the inhibition of the L-type Ca2+
      channel, and by the cross-bridge-dependent decrease in the Ca2+ sensitivity, as
      in low extracellular Ca2+ concentration.

PMID- 16565571
TI  - Pathophysiological basis for monitoring of whole heart conductance by 2-lead
      system.
AB  - BACKGROUND: The defibrillation threshold (DFT) is elevated during myocardial
      ischemia, but the underlying mechanism remains to be elucidated. The hypothesis
      tested by the present study was that whole heart conductance (WHC) is a
      determinant of DFT. METHODS AND RESULTS: WHC was monitored across the longest
      diameter of the isolated perfused rat heart, using a 2-electrode instrument under
      various conditions including ischemia-reperfusion (IR). In the control study, WHC
      was influenced by the conductivity and flow rate of the solution. In IR, WHC
      decreased immediately after the onset of perfusion arrest in a single exponential
      manner, then declined again gradually. The second decrease was augmented and
      accelerated by pretreatment with 1.0 mmol/L heptanol (p<0.005) or high-[Ca2+]e
      (p<0.001), and was attenuated and delayed by pretreatment with 1.0 micromol/L
      verapamil (p<0.01). WHC after reperfusion was greater than the pre ischemic
      level. The postischemic increase in WHC was proportional to the ischemic interval
      and tissue water content as assessed by desiccation method. CONCLUSION: Although
      time-dependent alterations in DFT in ischemic hearts may be attributable at least
      in part to dynamic changes in WHC, WHC should be interpreted carefully because it
      reflects many physiological factors such as coronary perfusion, electrical
      coupling of cardiac myocytes and tissue edema.

PMID- 16565573
TI  - Suspected takotsubo cardiomyopathy caused by withdrawal of bupirenorphine in a
      child.
AB  - A 2-year-old Japanese girl had transient left ventricular apical ballooning on
      echocardiography and ST-segment elevation and T-wave inversion on
      electrocardiogram after withdrawal of bupirenorphine and midazolam. The findings
      improved within 2 weeks. There are many case reports of adults with takotsubo
      cardiomyopathy but none in children. Takotsubo cardiomyopathy is not well known
      by pediatric cardiologists, so pediatric cases may have been overlooked.
      Awareness of a phenomenon similar to takotsubo cardiomyopathy, even in young
      children, may be important.

PMID- 16565572
TI  - Arrhythmogenesis in the short-QT syndrome associated with combined HERG channel
      gating defects: a simulation study.
AB  - BACKGROUND: This study aimed to show the mechanism how the HERG channel gating
      defects causes life-threatening arrhythmia in the short-QT syndrome, using a
      simulation model of ventricular action potentials (APs). METHODS AND RESULTS: To
      evaluate the electrophysiological consequences of the short-QT syndrome at the
      level of the cardiac AP, the Markov model of wild-type (WT) KCNH2 channel was
      modified to obtain a model of the KCNH2 channel with the N588K mutation
      associated with the short-QT syndrome. Two parameters (betai and betabeta) were
      changed to reconstruct the N588K mutant Markov model, which successfully
      reproduced the experimental results of voltage-clamp recordings. The WT and
      mutant models were then integrated into the Luo-Rudy theoretical model of the
      cardiac ventricular AP. Unexpectedly, 1 parameter change alone, which caused gain
      of function, could shorten the AP duration (APD) but failed to induce early after
      depolarizations (EADs). Only the condition with the combined gating defects could
      lead to EAD. CONCLUSIONS: Although the gain of function for KCNH2 shortened APD
      in the short-QT syndrome, this simulation study suggested that arrhythmogenesis
      was associated not only with gain of function, but also with accelerated
      deactivation of KCNH2.

PMID- 16565574
TI  - Deficiency of the Caenorhabditis elegans DNA polymerase eta homologue increases
      sensitivity to UV radiation during germ-line development.
AB  - Defects in the human XPV/POLH gene result in the variant form of the disease
      xeroderma pigmentosum (XP-V). The gene encodes DNA polymerase eta (Poleta), which
      catalyzes translesion synthesis (TLS) past UV-induced cyclobutane pyrimidine
      dimers (CPDs) and other lesions. To further understand the roles of Poleta in
      multicellular organisms, we analyzed phenotypes caused by suppression of
      Caenorhabditis elegans POLH (Ce-POLH) by RNA interference (RNAi). F1 and F2
      progeny from worms treated by Ce-POLH-specific RNAi grew normally, but F1 eggs
      laid by worms treated by RNAi against Ce-POLD, which encodes Poldelta did not
      hatch. These results suggest that Poldelta but not Poleta is essential for C.
      elegans embryogenesis. Poleta-targeted embryos UV-irradiated after egg laying
      were only moderately sensitive. In contrast, Poleta-targeted embryos UV
      irradiated prior to egg laying exhibited severe sensitivity, indicating that
      Poleta contributes significantly to damage tolerance in C. elegans in early
      embryogenesis but only modestly at later stages. As early embryogenesis is
      characterized by high levels of DNA replication, Poleta may confer UV resistance
      in C. elegans, perhaps by catalyzing TLS in early embryogenesis.

PMID- 16565575
TI  - Characteristics of scratching behavior induced by some chemical mediators in
      hairless mice.
AB  - To find the characteristics of scratching behavior in hairless mice (HR-1),
      compound 48/80 and some putative chemical mediators of allergic reaction were
      injected intradermally into the backs of mice, and the number of scratching
      behaviors was measured. As reference mice, NC/Nga, ICR, and ddY mice were used.
      Scratching behavior in HR-1 and ICR mice was increased dose-dependently by
      compound 48/80. The same result was also observed with NC/Nga and ddY mice.
      However, the response in NC/Nga and ddY mice was far less than those of HR-1 and
      ICR mice. Similar to NC/Nga and ddY mice, HR-1 mice showed less sensitivity to
      histamine than ICR mice. On the other hand, the HR-1 mice showed a high response
      to serotonin compared with those of the NC/Nga and ddY mice. The scratching
      behavior in HR-1 mice induced by substance P was increased, but the effect was
      less potent than those in NC/Nga, ICR, and ddY mice. These results suggest that
      the scratching behavior induced by compound 48/80 in HR-1 mice is mainly
      attributable to serotonin.

PMID- 16565576
TI  - Effects of intra-arterial urokinase on a non-human primate thromboembolic stroke
      model.
AB  - One of the most important prognostic factors in the thrombolytic treatment of
      acute ischemic stroke is to re-canalize. The purpose of this study was to
      evaluate the effectiveness and safety of urokinase in a primate thromboembolic
      stroke model. Thromboembolic stroke was accomplished via occlusion of the middle
      cerebral artery (MCA) obtained by injecting an autologous blood clot into the
      left internal carotid artery in 21 male cynomolgus monkeys. Animals were randomly
      assigned to the following treatment groups: Group 1: vehicle (saline), Group 2:
      urokinase (40,000 IU), Group 3: urokinase (120,000 IU,) over 2 or 6 h via intra
      internal carotid catheter starting 1 h after embolization, respectively. In the
      urokinase-treated groups, neurologic deficits were improved in consciousness and
      skeletal muscle coordination, but not sensory and motor systems. The infarction
      size in Group 2 (11.9 +/- 3.9% of the hemisphere) and 3 (7.6 +/- 2.5%) were
      significantly smaller than that (24.7 +/- 3.5%) in Group 1. However, 2 of 5
      animals in Group 3 died. In conclusion, urokinase improved neurologic deficits
      and reduced cerebral infarction on thromboembolic stroke in the cynomolgus
      monkey.

PMID- 16565577
TI  - Functional arterial baroreflex attenuates the effects of antihypertensive drugs
      in conscious rats.
AB  - The present work was designed to observe the influences of arterial baroreflex
      (ABR) function on cardiovascular effects produced by four routinely used
      antihypertensive drugs in conscious rats. A low ABR model was obtained by the
      performance of sinoaortic denervation (SAD). The doses of the four drugs were as
      follows: nifedipine (1.5, 3.0 mg/kg), captopril (50, 100 mg/kg), atenolol (10, 20
      mg/kg), and hydrochlorothiazide (20, 40 mg/kg). They were administered via an
      intra-gastric catheter. Compared with sham-operated rats, SAD significantly
      increased blood pressure variability about 2 times without modification of blood
      pressure level. The decrease in blood pressure level induced by the four tested
      drugs was larger in SAD rats than in sham-operated rats, which decreased to about
      10 mmHg. Pulse interval was not changed by the treatment of captopril, but
      prolonged by atenolol in both sham-operated and SAD rats. In sham-operated
      groups, treatment of both nifedipine and hydrochlorothiazide decreased pulse
      interval. Whereas in sinoaortic denervated ones, this tachycardia was prevented.
      Among the four tested drugs, it was found that only nifedipine and atenolol
      significantly decreased blood pressure variability in SAD rats. It can be
      concluded that arterial baroreflex function was able to attenuate the hypotensive
      effects produced by antihypertensive drugs in conscious rats.

PMID- 16565578
TI  - Physiological significance of thromboxane A(2) receptor dimerization.
AB  - The thromboxane A(2) receptor (TP), one of the G protein-coupled receptors
      (GPCRs), consists of two splicing variants, TPalpha and TPbeta, which differ in
      their C-terminal regions. In the present study, we investigated whether TPalpha
      and TPbeta formed homo- or hetero-dimers and whether the dimerization changed the
      function of TP. The immunofluorescent analysis using human embryonic kidney (HEK)
      293 cells expressing either FLAG-tagged TPalpha or TPbeta showed that TPalpha is
      mainly distributed on plasma membranes and TPbeta existed on plasma membranes and
      within the cells. Co-immunoprecipitation analysis using HEK293 cells expressing
      both TPalpha and TPbeta showed that TPalpha and TPbeta formed homo- and hetero
      dimers. U46619, a TP agonist, caused phosphoinositide hydrolysis and elevation of
      [Ca(2+)](i) in a concentration-dependent manner in Chinese hamster ovary (CHO)
      cells expressing TPalpha or TPbeta. The responses were observed to a greater
      extent in the cells expressing TPalpha than TPbeta. In the cells expressing both
      TPalpha and TPbeta, U46619-induced responses were observed to a lesser extent
      than in the cells expressing TPalpha alone. Furthermore, [(3)H]SQ29548 binding
      showed that the level of the cell surface expression of TP was the following
      order: the cells expressing TPalpha > TPalpha and TPbeta > TPbeta. These results
      indicate that TPalpha and TPbeta formed homo- and hetero-dimers, and TP-mediated
      signaling may be regulated by the hetero-dimer.

PMID- 16565579
TI  - Pharmacological, pharmacokinetic, and clinical properties of benidipine
      hydrochloride, a novel, long-acting calcium channel blocker.
AB  - Benidipine is a dihydropyridine-derived calcium channel blocker developed in
      Japan, with several unique mechanisms of action, that is, triple calcium channels
      (L, N, and T) blocking action with a membrane approach. Benidipine has relatively
      high vascular selectivity and is expected to show protective effects on vascular
      endothelial cells. Renal protective effects of benidipine also have been shown in
      several basic and clinical studies. Moreover, anti-oxidative action and enhancing
      nitric oxide production have been noted with this drug, following its cardio
      protective effects in patients with ischemic heart diseases. In fact, benidipine
      exerted a better prognostic effect than other calcium channel blockers in the
      therapy for patients with vasospastic angina. In addition, benidipine showed
      reliable antihypertensive, renoprotective effects if used in combination with
      angiotensin II type 1 receptor blockers (ARBs) when adequate anti-hypertensive
      effects are not achieved by ARBs alone, indicating that benidipine is an useful
      calcium channel blocker in combination therapy for hypertension. Benidipine was
      launched on the Japanese market 14 years ago, but few severe side effects have
      been reported, suggesting that this is a drug with established safety and long
      acting pharmacological effects.

PMID- 16565580
TI  - Nestin expression in vascular malformations: a novel marker for proliferative
      endothelium.
AB  - Cavernous angiomas (CAs) and arteriovenous malformations (AVMs) sometimes show
      growth or de novo appearance. Proliferative capacity of the endothelium is
      evident in such malformations. Intermediate filament nestin is a newly identified
      marker for proliferative endothelium, which was originally detected in the
      neuroepithelial stem cells of the embryonal central nervous system.
      Immunohistochemical analysis of nestin was evaluated as a marker for
      proliferative capacity of endothelial cells by comparison with proliferating cell
      nuclear antigen (PCNA). Sixteen of 27 CAs and 13 of 20 AVMs were positive for
      nestin. Likewise, 12 of 27 CAs and 10 of 20 AVMs were positive for PCNA. Nestin
      staining was stronger in the typical malformative vessels of CAs than in AVMs, in
      both the endothelial cells and the interstitial cells. Newly formed endothelial
      cells expressed nestin strongly in the reactive tissues including organizing or
      encapsulated hematomas. These results suggest that neovascularization occurs in
      the process of repeated bleeding and remodeling of hematomas.

PMID- 16565581
TI  - Skull base chordomas: management and results.
AB  - Growth patterns of skull base chordomas are related to important neurovascular
      structures. Local invasiveness results in "clinically malignant" behavior. A high
      rate of transient neurological deficits occurs following radical surgery. At our
      institution, the principle of radical removal is not followed at any price. This
      study compared the results of our management with recent series. Eleven patients,
      five females and six males aged 24-65 years (mean 41 years), underwent removal of
      skull base chordoma with size one <3 cm, five 3-5 cm, and five >5 cm. Mostly,
      standard operative approaches were chosen. All patients underwent postoperative
      radiotherapy. Resection was subtotal/partial in seven patients and total in four
      with no mortality. Neurological deterioration occurred due to transient cranial
      nerve deficits in six patients. Temporary surgical morbidity (including cranial
      nerve deficits) was observed in seven patients. Median Karnofsky performance
      status score improved compared to preoperative (80), early postoperative (70),
      and latest assessment (90) (median 36 months). Five patients underwent
      reoperation due to tumor recurrence after 4-48 months (mean 24 months). Most
      patients undergoing removal of skull base chordomas suffer from transient
      neurological deficits which are mainly nonsignificant as the patients return to
      preoperative functional status. The apparently high rate of incomplete tumor
      resection (64%) reflects the infiltrative behavior and relationship with
      neurovascular structures. The operative strategy should not be excessively
      aggressive at any price, but rather take into account the options of radiotherapy
      and observation of residual tumor.

PMID- 16565582
TI  - Spontaneous resolution of diabetes insipidus after pituitary stalk sectioning
      during surgery for large craniopharyngioma. Endocrinological evaluation and
      clinical implications for surgical strategy.
AB  - The mechanism of spontaneous resolution of diabetes insipidus (DI) was
      investigated after surgery for large craniopharyngioma. Twenty-two adult patients
      (mean age 48.9 years old), who underwent surgery via the anterior
      interhemispheric trans-lamina terminalis approach, were divided into three
      groups: Group I, the entire pituitary stalk was preserved (n = 2); Group II, the
      stalk was dissected distally from the tumor but ultimately sacrificed (n = 9);
      Group III, the stalk was not identified and was sacrificed (n = 11). All patients
      were discharged without neurological deficits 1 month after surgery. Four
      patients underwent gamma-knife treatment for residual tumor or recurrence.
      Postoperative endocrinological functions were normal in Group I, and no
      replacement therapy was required. Hormonal replacement for pan-hypopituitarism
      and DI was necessary in Groups II and III (mean follow-up period 5.9 years). DI
      resolved at 2.7 +/- 1.3 years after surgery in four patients in Group II, and a
      hypertonic saline infusion test revealed production of small amounts of intrinsic
      antidiuretic hormone (ADH). Urine osmolarity was high in the morning, and a
      significant increase in urinary osmolarity was noted after Pitressin injection.
      These results indicate induction of hypersensitivity of the distal renal tubules
      to small amounts of intrinsic ADH, resulting in decreased urinary output.
      Recovery from DI can be expected, despite permanent impairment of anterior
      pituitary function, if the pituitary stalk is dissected as distally as possible.

PMID- 16565584
TI  - Persistent primitive trigeminal artery aneurysm associated with cerebellar
      hemangioblastoma. Case report.
AB  - A 72-year-old man presented with a cerebellar vermian tumor manifesting as
      headaches and vertigo. Angiography disclosed a vascular tumor fed by the superior
      cerebellar artery and an aneurysm of a primitive trigeminal artery. The patient
      underwent right occipital craniotomy to remove the highly vascular tumor via an
      occipital transtentorial approach. Association of a cerebral aneurysm with a
      hemangioblastoma has been reported previously in only five cases. Only three
      aneurysms were located on the feeding artery. The aneurysm in this case was not
      on the feeding artery. Simple coincidence might account for this case.

PMID- 16565583
TI  - Evaluation of interhemispheric time difference by magnetoencephalography before
      and after total callosotomy. Two case reports.
AB  - Interhemispheric time difference (ITD) measured by electroencephalography (EEG)
      and magnetoencephalography (MEG) was compared to seizure outcome after
      callosotomy. Two patients with frequent drop attacks underwent simultaneous EEG
      and MEG before and after total callosotomy. ITDs in 30 bilateral synchronized
      (BS) discharges were calculated independently by EEG and MEG. As minimum
      transcallosal conduction time was suggested to be approximately 20 msec, BS
      discharges were classified into five categories according to ITD and side: left-
      or right-leading long (300 to 80 msec), left- or right-leading moderate (80 to 20
      msec), and negligible (<20 msec). In Case 1 before callosotomy, EEG detected 77%
      negligible and 23% right-leading moderate BS discharges, whereas MEG detected 30%
      and 63%, respectively. After callosotomy, drop attacks reduced remarkably and EEG
      and MEG detected no BS discharges. In Case 2 before callosotomy, EEG detected 77%
      negligible and 23% moderate BS discharges, whereas MEG detected 80% and 20%,
      respectively. After callosotomy, drop attacks recurred 2 months later and EEG and
      MEG detected left- and right-leading long BS discharges (63% by EEG and 56% by
      MEG). MEG detected a large number of BS discharges with moderate ITD before
      surgery in Case 1, suggesting that the transcallosal pathway was the main pathway
      for the synchronization, whereas the negligible ITD in Case 2 excludes
      transcallosal propagation. BS discharges with longer ITD after surgery in Case 2
      suggest a persistent poly-synaptic non-transcallosal pathway. MEG with higher
      spatial resolution than EEG may provide surgical indications for callosotomy.

PMID- 16565585
TI  - Atypical meningioma with large cyst. Case report.
AB  - A 29-year-old male presented with loss of consciousness and generalized seizure,
      followed by right hemiparesis and speech disturbance. Computed tomography and
      magnetic resonance imaging showed a solid, enhanced tumor with a cyst in the left
      frontal area with surrounding edema and mild mass effect. The cyst wall was also
      enhanced. The preoperative diagnosis was cystic falx meningioma. The tumor was
      totally resected, but most of the cyst wall adhered tightly to the surrounding
      brain and could not be removed. Histological examination revealed atypical
      meningioma and tumor cells in the cyst wall. The patient received local
      radiotherapy to the residual cyst wall with a total dose of 50 Gy.

PMID- 16565586
TI  - Pituicytoma. Two case reports.
AB  - Pituicytoma is a rare tumor in the sellar or suprasellar region with distinct
      histological characteristics of glial neoplasm. A 42-year-old woman presented
      with a history of amenorrhea and vertigo, and a 62-year-old woman presented with
      mild headache. Both patients had mild hyperprolactinemia and one had mild
      anterior pituitary dysfunction. They underwent transcranial partial resection of
      a suprasellar tumor. The tumors were characterized by storiform pattern of
      elongated cells immunoreactive for S-100 protein and glial fibrillary acidic
      protein. Ultrastructural study showed abundant cytoplasmic intermediate filaments
      and tumor/blood vessel basal lamina, but no desmosomes between tumor cells. The
      residual tumors showed no changes in size without adjuvant therapy at 56 and 18
      months after surgery. Pituicytoma is a glial neoplasm of adults with low
      proliferative activity. Patients often present with visual symptoms or anterior
      pituitary dysfunction. Symptoms and signs of neurohypophysis are rare.
      Neuroimaging reveals an intra- or suprasellar mass with non-specific features.
      The prognosis and role of adjuvant therapy remain unclear for this discrete
      noninfiltrative glioma.

PMID- 16565587
TI  - Lumbar spinal extradural angiolipomas. Two case reports.
AB  - Spinal extradural angiolipomas are benign tumors mostly localized in the thoracic
      region. A 50-year-old woman and a 36-year-old man presented with rare lumbar
      spinal angiolipoma manifesting as low back pain but without neurological signs.
      Magnetic resonance imaging showed lumbar extradural tumors at the L4-5 and L1-2
      levels, respectively. Each patient underwent complete surgical resection of the
      epidural tumors. Histological examination revealed characteristics of
      angiolipomas in both tumors. The symptoms of both patients improved
      postoperatively and no recurrence of the tumors was found 1 year after surgery.

PMID- 16565588
TI  - Stevens-Johnson syndrome associated with intravenous acetazolamide administration
      for evaluation of cerebrovascular reactivity. Case report.
AB  - A 62-year-old man with left middle cerebral artery stenosis manifesting as
      transient ischemic attack underwent evaluation of regional cerebrovascular
      reactivity to acetazolamide using single photon emission computed tomography.
      Three days after intravenous administration of acetazolamide, erythematous
      eruptions of various sizes appeared on his back and spread over almost his entire
      body. Subsequently, painful ulcerations developed on his lips, and oral and nasal
      mucosa, and the conjunctiva became hyperemic, indicating Stevens-Johnson
      syndrome. The results of the lymphocyte transformation test were positive to only
      acetazolamide. Stevens-Johnson syndrome, also known as erythema multiforme major,
      can be life-threatening, and may be induced by intravenous administration of
      acetazolamide.

PMID- 16565589
TI  - Surgical removal of a live worm by stereotactic targeting in cerebral
      sparganosis. Case report.
AB  - A 64-year-old man presented with generalized tonic clonic convulsion followed by
      weakness of the right lower extremity. He had a medical history of hypertension,
      hyperlipidemia, and right cerebellar infarction. Computed tomography (CT) showed
      a small high density nodule with an enhanced perifocal low density area in the
      left occipital lobe. T1-weighted magnetic resonance (MR) imaging showed a ring
      shaped and partial string-like nodule with enhancement by gadolinium. T2-weighted
      MR imaging showed the white matter of the left occipital lobe as high intensity.
      CT and MR imaging seemed to indicate metastatic brain tumors, although cortical
      atrophy and ventricular dilation were recognized. Left parietal craniotomy was
      performed under stereotactic targeting to obtain a definitive diagnosis. During
      manipulation at the center of the targeted lesion, a white, tape-like body was
      found and recognized to be a live worm. Serological testing revealed strong
      immunopositivity against Spirometra mansoni. The infection route in the present
      case was probably through eating raw chicken meat. Cerebral sparganosis is
      extremely rare but should be considered in the differential diagnosis of
      metastatic brain tumors, especially in endemic areas.

PMID- 16565590
TI  - Impaired left ventricular filling in patients with essential hyperhidrosis: an
      echo-Doppler study.
AB  - Essential hyperhidrosis is a well recognized dermatologic and neurologic
      disorder, characterized by excessive sweating of the eccrine sweat glands. It is
      also associated with cardiac autonomic dysfunction because sympathetic fibers to
      eccrine glands of palms of the hand arise from stellate and upper thoracic
      ganglia, which also innervate the heart. In this study, we investigated cardiac
      function in patients with essential hyperhidrosis by conventional and tissue
      Doppler imaging methods. Eighteen subjects with essential hyperhidrosis and
      eighteen control subjects were included in this study. Pulsed-wave Doppler
      parameters of the left and right ventricles, which represent diastolic filling
      abnormalities, were obtained by conventional Doppler and tissue Doppler imaging.
      Isovolumetric relaxation time, isovolumetric contraction time, ejection time and
      myocardial performance index were also calculated. Mitral inflow peak early
      (E(M)) and late (A(M)) velocities and E(M)/A(M) ratio, which represent diastolic
      filling of left ventricle, were significantly lower in hyperhidrotic subjects
      than in controls. Also, mitral lateral annulus early and late velocities and
      early/late velocity ratio, reflecting diastolic filling of left ventricle, were
      significantly lower in hyperhidrotic subjects than those of controls. However,
      there were no differences between hyperhidrotic subjects and control subjects
      with regard to the other echocardiographic indices of left and right ventricle
      diastolic functions. In conclusion, decreased mitral inflow suggests left
      ventricle diastolic dysfunction in patients with essential hyperhidrosis. This
      indicates that hyperactivity of sympathetic nervous system in patient with
      hyperhidrosis may alter cardiac function in long term.

PMID- 16565591
TI  - Transthoracic echocardiographic predictors of the left atrial appendage
      contraction velocity in stroke patients with sinus rhythm.
AB  - Systemic embolization is a potential complication in patients with thrombi
      situated in the left atrium and particularly, in the left atrial appendage (LAA).
      Reduced LAA contraction velocities, determined by the transesophageal
      echocardiography (TEE), are associated with increased risk of LAA spontaneous
      echocontrast and thrombus formation, and a history of systemic embolism. However,
      TEE remains a semi-invasive procedure, limiting its serial application as a
      screening tool. Therefore, it is desirable to obtain information regarding LAA
      function by transthoracic echocardiography in patients having cardioembolic
      stroke. The present study was designed to investigate various echocardiographic
      variables for patients with stroke to predict LAA dysfunction, reflected as
      reduced LAA contraction velocity. We studied a total of 61 patients with newly
      diagnosed acute embolic stroke (42 patients) and transient ischemic attack (19
      patients). Computerized tomographic scanning was performed for the diagnosis of
      embolic stroke. Left atrial functional parameters determined by transthoracic
      echocardiography, such as left atrial active emptying fraction and acceleration
      slope of mitral inflow A wave, had significant correlations with the LAA
      contraction velocity (r = 0.57, p < 0.001; r = 0.54, p < 0.001, respectively).
      Left atrial volume index, left atrial active emptying volume and left atrial
      fractional shortening were also correlated with LAA contraction velocity (r = 
      0.44, p < 0.001; r = 0.38, p = 0.003; r = 0.37, p = 0.004, respectively). In
      conclusion, transthoracic echocardiography can provide valuable and reliable
      information about the LAA contraction velocity in stroke patients with sinus
      rhythm. This finding gives new insights for the appropriate strategy in the
      evaluation of an acute ischemic stroke.

PMID- 16565592
TI  - Predictive factors for acute esophageal toxicity in thoracic radiotherapy.
AB  - Acute esophageal toxicity (AET) is a common complication and dose-limiting
      toxicity in thoracic radiotherapy. Previous studies demonstrated several clinical
      and dosimetric parameters of AET in patients with lung cancer. However, there are
      few reports dealing with these variables in intra-thoracic malignancies,
      including lung cancer and other thoracic malignancy. The purpose of this study
      was to evaluate the clinical and dosimetric factors associated with AET in
      patients with intra-thoracic malignancies. We examined 61 patients with intra
      thoracic malignancies treated with radiotherapy: 34 patients with non-small-cell
      lung cancer (55%), 9 cases with small-cell lung cancer (15%), 7 cases with thymic
      cancer (11%), 4 thymomas (7%), 2 malignant lymphomas (3%), one seminoma (2%), one
      liposarcoma (2%), and 3 cases of other malignancies (5%). Radiotherapy was
      performed with a median dose of 60 Gray (Gy) (range 40-67 Gy). AET was graded
      according to the Radiation Therapy Oncology Group (RTOG) criteria. The following
      parameters were analyzed with respect to associations with AET by univariate and
      multivariate analyses: age, gender, thoracic surgery before radiotherapy,
      concurrent chemotherapy, duration of radiotherapy, maximum esophageal dose, mean
      esophageal dose, and percentage of esophageal volume receiving from 10 Gy (V10)
      to 65 Gy (V65), in 5-Gy increments. 43 patients (70%) developed AET: 36 patients
      (59%) with AET of RTOG Grade 1, 7 patients (11%) with Grade 2, and no patients
      (0%) with Grade 3 or worse. On multivariate analysis, V35 > 30% was the most
      statistically significant factor associated with mild AET (p = 0.013). Our
      findings provide a better understanding of the factors related to AET, and might
      be useful in designing a treatment plan to prevent severe esophageal toxicity.

PMID- 16565593
TI  - Contribution of intramuscular oxidative metabolism to total ATP production during
      forearm isometric exercise at varying intensities.
AB  - It is not fully clear whether intramuscular oxidative metabolism contributes to
      total adenosine triphosphate (ATP) production during forearm isometric exercise
      at varying intensities. We tested hypothesis that oxidative metabolism with
      intramuscular O2 contributes to lessen the dependence on anaerobic metabolism, in
      particular phosphocreatine (PCr) breakdown. Seven male subjects were tested for
      changes in muscle oxygenation (MO2) and high-energy phosphates in forearm flexor
      muscles at rest and during exercise under arterial occlusion by 31-phosphorus
      magnetic resonance spectroscopy (31P-MRS) and near infrared spectroscopy (NIRS).
      Isometric wrist flexion exercise was performed for 1 min or until exhaustion at
      intensities corresponding to 30%, 50% and 70% of maximal voluntary contraction
      (MVC) under intramuscular O2 (Intramuscular O2-Ex) and anaerobic (Anaero-Ex)
      conditions. Oxidative ATP production in Intramuscular O2-Ex was calculated as
      0.05 +/- 0.01 mM/s for 30%MVC, 0.08 +/- 0.01 mM/s for 50%MVC and 0.11 +/- 0.01
      mM/s for 70%MVC. At a lower intensity (30%MVC), PCr breakdown rate (0.17 +/- 0.02
      mM/s) of Anaero-Ex was significantly higher than the rate (0.13 +/- 0.01 mM/s) of
      Intramuscular O2-Ex (p < 0.05). There was no significant difference in ATP
      production rates through PCr breakdown and glycolysis between Intramuscular O2-Ex
      and Anaero-Ex at the higher intensities (50% and 70%MVC). In conclusion,
      intramuscular oxidative metabolism plays a significant role in reducing the
      dependence on PCr breakdown during isometric exercise at a lower intensity
      (30%MVC).

PMID- 16565594
TI  - Acupuncture stimulates the release of serotonin, but not dopamine, in the rat
      nucleus accumbens.
AB  - Acupuncture has been introduced as one of the available therapies widely used in
      alternative medicine, but it has not achieved widespread acceptance with
      scientific evidence. Furthermore there are still many unanswered questions about
      the basic mechanisms of acupuncture. To investigate the neuropharmacological
      mechanisms of oriental acupuncture, we studied the acupuncture-induced changes of
      in vivo monoamine release in the rat brain. A microdialysis guide cannula was
      implanted into the nucleus accumbens (ACC), which plays an important role in the
      brain reward system. Acupuncture treatment at the unilateral or bilateral Shenshu
      (bladder urinary channel 23) acupoints, located on the both sides of the spinous
      processes on the lower back, was carried out for 60 min in freely moving rats,
      and the dopamine (DA) and serotonin (5-HT) contents of the microdialysates in the
      ACC were measured simultaneously. In rats subjected to acupuncture at bilateral
      Shenshu acupoints, increases of 5-HT release in the ACC were observed at 20 min
      of acupuncture treatment and continued until 40 min after acupuncture was ended.
      Acupuncture at a unilateral Shenshu acupoint increased the release of 5-HT at 20
      min compared with that in the sham-control group. Five-HT release returned to the
      baseline level at 120 min. The effects of acupuncture at bilateral Shenshu
      acupoints on the release of 5-HT in the ACC were greater than that of unilateral
      acupuncture treatment. In contrast, DA release in the ACC was not changed
      following acupuncture treatment. Effective acupuncture increased and prolonged
      the activity of serotonergic neurons in the reward system pathway of the brain.
      This suggests that oriental acupuncture therapy may be effective for the
      treatment of emotional disorders, drug abuse and alcoholism.

PMID- 16565596
TI  - Inhibition of Oct4 expression in mouse preimplantation embryos using morpholino
      antisense oligonucleotides.
AB  - Morpholino oligonucleotides (MO) can induce gene silencing by binding to a target
      mRNA and inhibiting its translation, and this technique has been especially
      successful in studies of embryonic development in various vertebrates. But in
      mice MO-induced downregulation of target genes has not been widely reported. In
      this study, we examined whether MO delivery using ethoxylated polyethylenimine
      (EPEI) delivery reagent is useful for silencing gene expression in the mouse
      preimplantation embryo, by targeting endogenous gene Oct4. To optimize the
      conditions for MO delivery, we examined the MO concentration, the EPEI
      concentration, the treatment time, and the number of MO treatments. The MO
      treatment was performed at the 2-cell, the morula, the blastocyst, and the
      hatched blastocyst stage. We first determined the optimal conditions for MO
      delivery into the nucleus using fluorescein isothiocyanate (FITC)-labeled MO, and
      demonstrated that treatment with a combination of 20 microM MO and 0.56 microM
      EPEI for 3 hrs produced effective MO delivery. MO-induced downregulation of Oct4
      was then examined. Two-step MO treatment at the 2-cell and blastocyst stages
      successfully suppressed Oct4 expression. This MO treatment resulted in marked
      reduction of Oct4 protein at the blastocyst stage. After cultivation of
      blastocysts for further 4 days, derivatives of embryos either differentiated to
      trophoblastic cells or showed developmental arrest at the blastocyst. This
      phenocopy is similar to Oct4-deficient embryos. Overall, our results indicate
      that MO delivery with EPEI is an effective tool for analyzing gene function in
      mouse preimplantation embryos.

PMID- 16565595
TI  - High seroprevalence of Helicobacter pylori in chronic bronchitis among Chinese
      population.
AB  - An increased seroprevalence of Helicobacter pylori (H. pylori), especially high
      virulent cytotoxin-associated gene-A (CagA) positive strains, has been found in
      many extragastrointestinal disorders. Moreover, it has been reported that the
      risk of chronic bronchitis may be increased in H. pylori infected patients.
      However, until now there are no data regarding the relationship between H. pylori
      infection and chronic bronchitis among Chinese population. Therefore the aim of
      the present study was to assess the seroprevalence of H. pylori and in particular
      of CagA positive virulent strains in patients with chronic bronchitis among
      Chinese population. We evaluated 46 patients with chronic bronchitis, 48 age- and
      sex-matched patients with peptic ulcer and 48 healthy control subjects. All
      enrolled subjects underwent a serologic test for H. pylori IgG and CagA by enzyme
      linked-immunosorbent assay (ELISA). There was no significant difference in the
      seropositivity for these parameters between chronic bronchitis and peptic ulcer
      groups (86.9% vs 89.6% for anti-H. pylori IgG and 67.4% vs 72.9% for anti-H.
      pylori-CagA IgG). However, these serological parameters were significantly higher
      in the patients with chronic bronchitis or peptic ulcer than those in control
      group, who showed 60.4% for anti-H. pylori IgG seropositivity and 20.8% for anti
      H. pylori-CagA IgG seropositivity. Among the patients with chronic bronchitis, no
      significant difference was found in these serological parameters between the
      current cigarette smokers and never smokers. This is the first report of a high
      seroprevalence of H. pylori infection in chronic bronchitis among Chinese
      population.

PMID- 16565597
TI  - Osteosarcoma in a patient with neurofibromatosis type 1: a case report and review
      of the literature.
AB  - Neurofibromatosis type 1 (NF1) or von Recklinghausen's disease is a genetic
      disease generally characterized by cafe-au-lait spots and neurofibromas.
      Malignant tumors of the nervous system, such as malignant schwannomas, gliomas,
      or astrocytomas, have been well known to coexist with neurofibromatosis. However,
      occurrence of malignant tumors unrelated to the nervous system is rare. We report
      an unusual case of a 29-year-old NF1 female suffering from malignant peripheral
      nerve sheath tumor (MPNST) that eventually developed osteosarcoma in the proximal
      femur. Osteosarcoma is the most common high-grade malignant bone tumor in which
      the neoplastic cells produce osteoid. At 23 and 24 years old, she underwent
      excision of MPNST in the left posterior thigh. No osteosarcomatous portion was
      identified in these specimens. The patient underwent postoperative chemotherapy.
      At 29, left proximal thigh pain and swelling appeared. Computed tomography
      demonstrated cortical bone destruction in the left proximal femur where MPNST
      occurred. Magnetic resonance imaging revealed extraskeletal growth of the tumor.
      Bone scintigraphy demonstrated increased uptake in the left proximal femur. Hip
      disarticulation was performed. The removed tumor was composed of highly
      anaplastic cells. Lace-like irregular osteoid formation was observed among the
      tumor cells. MPNST component was totally absent. The tumor was diagnosed as
      osteoblastic type osteosarcoma. Two months after disarticulation the patient died
      of bilateral pulmonary metastasis. The correlation between the histogenesis of
      osteosarcoma and the genetic abnormality in NF1 patients has not been elucidated,
      but the finding of osteosarcomatous transformation in this case suggests the
      divergent cellular differentiation to mesenchymal malignant tumors of
      neuroectodermal tissue in NF1 patients.

PMID- 16565598
TI  - Serum antibody against granulocyte/macrophage colony-stimulating factor and KL-6
      in idiopathic pulmonary alveolar proteinosis.
AB  - Here we describe a case of idiopathic pulmonary alveolar proteinosis (I-PAP), in
      which anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibody and
      high level of KL-6 were found in the serum. Anti-GM-CSF antibody is responsible
      for I-PAP, and KL-6 is a serum marker for the activity of diffuse interstitial
      lung disease. A 38-year-old woman, who had no symptoms, was found to have an
      abnormal shadow on chest radiograph 5 years previously at a health check up.
      Chest radiograph showed a patchy shadow in the left lower lung field.
      Thoracoscopic biopsy was performed because the shadow had gradually expanded
      during the 5 years. Histological examination revealed proteinous material filling
      the alveoli and positive staining by the PAS method, suggesting PAP. Anti-GM-CSF
      antibody and a high level of KL-6 were detected in the serum at the time of
      diagnosis. Three years later, the shadow disappeared spontaneously. During this
      period, the level of KL-6 dramatically decreased, although that of GM-CSF
      antibody remained unchanged. The present case suggests that the serum level of
      the anti-GM-CSF antibody represents a useful marker for the diagnosis but not for
      follow-up of the clinical course. On the contrary, KL-6 is an excellent marker
      for the assessment of the clinical course of I-PAP.

PMID- 16565599
TI  - Effective treatment with cyclosporine A of a child with systemic lupus
      erythematosus resistant to cyclophosphamide pulse therapy.
AB  - Intermittent intravenous cyclophosphamide pulse therapy (IVCY) has been reported
      to be effective for the treatment of refractory systemic lupus erythematosus
      (SLE). However, there is a proportion of patients with SLE, who are IVCY
      resistant and need a long-term therapy to sustain the remission. We report here a
      case of a 6-year-old Japanese girl with SLE refractory to IVCY. She suffered from
      persistent hypocomplementemia and recurrent flares despite receiving
      methylprednisolone pulse, mizoribine pulse and IVCY therapy. Administration of
      cyclosporine A (CsA) was, therefore, initiated. Within 2 months of the start of
      CsA administration, the serum levels of C3, C4 and complement hemolytic activity
      began to increase rapidly, and finally returned to the normal levels. The serum
      anti-dsDNA antibody titer was decreased significantly after the initiation of
      this treatment. The prednisolone dose could be successfully tapered without
      precipitation of any flares. No adverse effects of CsA were observed. Based on
      these clinical observations, we suggest that CsA might be an effective treatment
      option for selected cases of refractory SLE.

PMID- 16565601
TI  - [Acute toxic hepatitis: RUCAM application to drug-induced liver injury and its
      limitations].

PMID- 16565602
TI  - [Role of PXR and CAR in cholestasis].
AB  - Cholestatic liver diseases are characterized by impairments of bile flows and
      accumulations of biliary constituents such as bile acids and bilirubin. The
      changes of phase I and II metabolism and the hepatobiliary transport system
      minimize cholestatic liver injury. These adaptive responses are transcriptionally
      regulated by several nuclear receptors. Recent studies have revealed that the
      pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are key
      nuclear receptors for regulating many of the adaptive responses noted in
      cholestasis. PXR and CAR coordinately regulate not only bile acid metabolism and
      transport, but also bilirubin clearance. PXR and CAR ligands may be useful in the
      future for the treatment of cholestatic liver disease.

PMID- 16565603
TI  - [Insulin resistance in non-alcoholic fatty liver disease].
AB  - Insulin resistance is the pathophysiological hallmark of various kinds of
      clinical diseases, including non- alcoholic fatty liver disease. Insulin
      resistance is the common characteristic of metabolic syndrome and its related
      features. Insulin resistance is a systemic disease that affects the nervous
      system, muscles, pancreas, kidney, heart and immune system, in addition to the
      liver. A complex interaction between genes and environment factors enhances
      insulin resistance and the phenotypic expression of NAFLD (non- alcoholic fatty
      liver disease) in individual patients. Advanced fibrotic liver disease is
      associated with many features of metabolic syndrome, and the risk of progressive
      liver disease should not be underestimated for the individuals suffering with
      metabolic disorders. Abnormalities of insulin signaling can cause the state of
      insulin resistance, but there is no clear cut scientific evidence that distorted
      insulin signaling is the primary pathophysiological defect. Increased adipose
      tissue mass can cause peripheral tissue insulin resistance via the changes of the
      adipocytokine secretory patterns. We discuss in this article the sequences of the
      insulin signaling cascades and the possible molecular targets of insulin
      resistance, the humoral "cross talk" between the distorted secretory patterns of
      the adipocytokines, and the peripheral tissue insulin resistance along with the
      pathophysiology of NAFLD.

PMID- 16565604
TI  - [Peginterferon alfa-2a plus ribavirin for initial treatment of chronic hepatitis
      C in Korea].
AB  - BACKGROUND/AIMS: Combination therapy with peginterferon and ribavirin is a
      standard therapy for western patients with chronic hepatitis C; however, its
      efficacy remains unclear in East Asian patients. We evaluated the efficacy and
      safety of administering peginterferon alfa-2a plus ribavirin in native Korean
      patients with chronic hepatitis C. METHODS: Seventy-five patients with detectable
      HCV RNA (52.0% male, median age: 50.8 years) were eligible for the study. The
      patients were treated with peginterferon alfa-2a 180 mcg/week plus ribavirin 800
      mg/day for 24 weeks (for genotype non-1, n=46) or 1000-1200 mg/day for 48 weeks
      (for genotype 1, n=29). The early virologic response (EVR), the end of treatment
      virologic response (ETVR), the sustained virologic response (SVR), the
      biochemical response and the adverse event were analyzed. RESULTS: EVR was seen
      in 86.2% of the patients with genotype 1. The ETVR was 58.6% in the genotype 1
      group and 84.8% in the genotype non-1 group (P=0.02). The overall SVR was 70.7%:
      55.2% in the genotype 1 group and 80.4% in the non-1 group (P=0.04). The
      sustained biochemical response was 64.0%. Multivariate analysis showed that the
      baseline HCV RNA level (Odds ratio: 0.045, 95% CI: 0.011-0.183, P<0.001) and
      genotype (Odds ratio: 0.247, 95% CI: 0.063-0.969, P=0.045) had an independent
      effect on the SVR. Neutropenia, anemia, flu-like symptoms and itching were the
      common adverse events. Aggravated liver function led to discontinuation of
      therapy for six patients. Dose modification in twenty-nine patients was effective
      without producing a significant reduction of the SVR. CONCLUSIONS: Our data
      suggest that the efficacy of peginterferon plus ribavirin therapy in Koreans is
      comparable to those from studies on Western patients as an initial treatment for
      chronic hepatitis C patients. The baseline HCV RNA level and the genotype can be
      significant factors influencing the SVR.

PMID- 16565605
TI  - [Survival analysis for patients with hepatocellular carcinoma according to stage,
      liver function and treatment modalities].
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is 3rd leading cause of cancer in
      Korea and the prognosis for HCC patients is poor. For assessing the present
      treatment outcome, this study analyzed the three-year survival rate (3-YSR) and
      the prognostic factors for patients with HCC in Korea. METHODS: Between November
      2000 and December 2003, 905 patients with HCC who were diagnosed and treated at
      the National Cancer Center Korea were enrolled in this study. The clinical
      variables, tumor characteristics and survival periods were analyzed. RESULTS: The
      mean age of all patients was 56.2+/-10.3 years and 732 (80.9%) patients were male
      (M:F=4.2:1). 508 (56.1%) patients died and the median survival period was 15.3
      months. The overall 3-YSR of the patients with modified UICC stage I, II, III,
      IVa and IVb were 67.4%, 65.2%, 30.7%, 9.0% and 5.0%, respectively. The modified
      UICC stage could not differentiate stage I from II, and stage IVa from IVb, on
      the 3-YSR. The 3-YSR of the Child-Pugh class A patients with modified UICC stage
      I or II was 85.4% by surgical resection and it was 69.6% by transcatheter
      chemoembolization (TACE), respectively (P= .461), and those values for patients
      with stage III were 49.2% and 36.8%, respectively (P=.081). As compared with
      systemic chemotherapy or conservative therapy, TACE increased the survival rate
      more for the Child-Pugh class A patients with stage IV. The independent
      prognostic factors were serum AFP, portal vein thrombosis, the Child-Pugh
      classification and the stage of HCC. CONCLUSIONS: This follow-up study will be
      helpful in assessing the results of treatments for HCC and it will provide data
      for the establishment of a more effective treatment strategy.

PMID- 16565606
TI  - [Clinical features of liver abscess developed after radiofrequency ablation and
      transarterial chemoembolization for hepatocellular carcinoma].
AB  - BACKGROUND/AIMS: Radiofrequency ablation (RFA) and transarterial
      chemoembolization (TACE) have been applied for treating hepatocellular carcinoma
      (HCC), but procedure-related complications can be a serious problem. This study
      was conducted to evaluate the clinical features of HCC patients who developed
      liver abscess after RFA and TACE, as compared to those patients without
      malignancy. METHODS: In our center, from December 1999 to March 2004, 31 cases of
      liver abscess developed after local treatment of HCC (13/751 after RFA and
      18/8417 after TAE), which correspond to 5.1% of the total cases (602) of liver
      abscess. We evaluated the patients' clinical features, the abscess
      characteristics, the bacteriology, treatment modality, hospital days and
      mortality, as compared to those characteristics of 263 abscess patients without
      malignancy. RESULTS: The time required to diagnose liver abscess was longer in
      the TACE group (24.8+/-16.5 days) compared to that of the other two groups
      (12.2+/-9.0 days in the RFA group, 9.6+/-7.5 days in the controls, P=0.001). Gas
      forming liver abscess is most frequently found in the RFA groups (76.9%). There
      were more hospitalized days for the TACE groups than for the RFA group and the
      controls (34.7+/-19.8 vs. 15.2+/-9.2 vs. 18.6+/-10.9 days, respectively,
      P<0.001). Two patients (11%) in the TACE group died of sepsis and liver failure.
      CONCLUSIONS: For the patients with prolonged fever after RFA and especially after
      TACE for HCC, a diagnosis of liver abscess should be suspected earlier to reduce
      the morbidity and mortality due to liver abscess per se and also the sepsis
      related decompensation of the liver.

PMID- 16565607
TI  - [Effect of low dose 5-fluorouracil and cisplatin intra-arterial infusion
      chemotherapy in advanced hepatocellular carcinoma with decompensated cirrhosis].
AB  - BACKGROUND/AIMS: Advanced hepatocellular carcinoma (HCC) with portal vein
      thrombosis (PVT) has a poor prognosis. The aim of this study was to evaluate the
      efficacy and safety of repeated arterial infusions of low dose cisplatin and 5
      fluorouracil (FU) in patients with advanced HCC with decompensated cirrhosis.
      METHODS: Between January 1995 and December 2003, a total of 79 decompensated
      cirrhotic patients having HCC and PVT were enrolled and divided into 2 groups.
      Group 1 (n=40) received intra-arterial infusion chemotherapy with cisplatin (10
      mg for 5 days) and 5-FU (250 mg for 5 days) via an implanted chemoport every 4
      weeks' and group 2 (n=39) was managed with only conservative treatment. RESULTS:
      The two groups were well matched with respect to the features relating to the
      prognosis, including age, gender and the Child- Pugh class. Although diffuse
      tumor involvement, main portal vein tumor thrombosis and bi-lobar involvement
      were more frequent in group 1, the median survival period of group 1 was
      significantly longer than group 2 (5 months vs. 3 months, respectively, P=0.016).
      Also, the 1-year survival rate of group 1 (7.5%) was higher than that of group 2
      (5.1%) (P=0.016). When we analyzed the patients with the Child class B, the
      survival benefits of intra-arterial chemotherapy were more significant (P=0.008).
      CONCLUSIONS: Intra-arterial chemotherapy consisting of low dose 5-FU and
      cisplatin achieved favorable results for advanced HCC patients who had
      decompensated cirrhosis, and it showed better survival in selected patients. This
      therapy may be useful as a palliative treatment for HCC patients with
      decompensated cirrhosis.

PMID- 16565608
TI  - [Clinical experience of 48 acute toxic hepatitis patients].
AB  - BACKGROUND/AIMS: Although many individual cases of toxic hepatitis have been
      reported in Korea, there are few comprehensive systematic studies on acute toxic
      hepatitis. The first aim of this study is to investigate the frequency and
      clinical characteristics of acute toxic hepatitis patients. The second aim of
      this study is to investigate the efficacy of steroid therapy for immunoallergic
      idiosyncrasy. METHODS: Between March 1998 and March 2004 forty eight patients
      were included in this study. The medical records were reviewed retrospectively.
      Acute toxic hepatitis was diagnosed by score of more than 3 in RUCAM criteria.
      All the patients were tested for hepatitis A, B and C. Other tests included
      antibodies to CMV and EBV, ANA, AMA and SMA. RESULTS: Seventy-three percent of
      the patients were female and the mean age of the patients was 47. Twenty cases of
      acute toxic hepatitis (42%) were related to prescribed medications. The other
      causes were herbs (35%) and traditional therapeutic preparations (23%). Common
      symptoms were jaundice (35%), fatigue (10%), fever (9%) and abdominal pain (9%).
      The biochemical pattern of hepatotoxicity was divided into three groups:
      hepatocellular (81%), mixed (13%), and cholestatic types (6%). Three patients who
      have prolonged and severe jaundice were classified into immunoallergic
      idiosyncrasy based upon clinical and histologic findings. Prednisolone was
      prescribed in all three cases whose bilirubin levels had been higher than 15
      mg/dL for at least 7 days. Jaundice and the laboratory findings rapidly improved
      within 8 days since the treatment began. CONCLUSIONS: In a demographic point of
      view, most patients of acute toxic hepatitis were middle aged women. Jaundice was
      the most commonly observed symptom. Prescribed drugs were the most common cause
      of acute toxic hepatitis. Although most cases of toxic hepatitis will recover
      with supportive care after cessation of the causative agent, steroid treatment
      may be helpful for the patients with severe jaundice patients who have
      immunoallergic idiosyncrasy.

PMID- 16565609
TI  - [Clinical features of fulminant hepatic failure in a tertiary hospital with a
      liver transplant center in Korea].
AB  - BACKGROUND/AIMS: Striking geographic differences have been noted in the etiology
      of fulminant hepatic failure (FHF). The prognosis of patients with FHF who do not
      receive liver transplantation in a timely manner is quite dismal. This study
      intended to identify the etiology and outcome of FHF in Korean adults and to
      examine the role of urgent living-donor liver transplantation (LDLT) for treating
      this unique situation. METHODS: We identified all the adult FHF patients who were
      referred to our unit between 1999 and 2004. FHF was defined as severe acute
      hepatitis complicated by the rapid development of hepatic encephalopathy within 8
      weeks of the initial symptoms in the patients without a previous history of liver
      disease. RESULTS: One hundred fourteen patients (47 males and 67 females) were
      identified. The mean age was 39.5+/-15.3 years. Drugs were the most common cause
      (28.1%) of FHF (herbal medications, 9.6%), and acute viral infection accounted
      for 23.7% (HBV accounted for 15.8%). Indeterminate etiologies were noted in 34%.
      The 90-day survival rate of the nontransplant group was only 15%. Fourteen
      patients received liver transplants (13 right-lobe LDLT, 1 cadaveric whole
      liver), and 12 of these (85.7%) survived and showed good graft function during 22
      months of median follow-up. CONCLUSIONS: Although the causes of FHF in Korea were
      diverse, HBV infection and herbal medications were responsible for a significant
      proportion of the cases. Since urgent LDLT improved the overall survival rate of
      patients with FHF, this should be considered as an important treatment option for
      patients suffering with FHF.

PMID- 16565610
TI  - [Protein expression profiles in a rat cirrhotic model induced by thioacetamide].
AB  - BACKGROUND/AIMS: The reactive oxygen species from thioacetamide (TAA) induces rat
      liver cirrhosis that resembles the human disease, and it can serve as a suitable
      animal model for studying human liver cirrhosis. The aim of this study was to
      identify the molecular protein signatures via a proteomics approach with using a
      rat model with TAA-induced liver cirrhosis. METHODS: Male Wistar rats were
      treated with 0.3 g/L TAA in their drinking water. The animals were then
      sacrificed at 9 and 30 weeks after TAA administration. The development of liver
      cirrhosis was observed with histological study. The livers were processed for
      proteins extraction and the proteins were analyzed by 2-dimensional
      electrophoresis. The proteins were identified by matrix-assisted laser desorption
      ionizing time-of-flight mass spectrometry and this was validated by
      immunohistochemical staining. RESULTS: On the proteomics analysis of the liver
      tissues, a total of 88 proteins showed significant change in their expression
      between the controls and the cirrhotic rats. When the proteins were categorized
      by their function, they included ECM/cellular skeleton, cell proliferation/death
      signal, metabolism, DNA damage/stress and immune response related proteins. The
      level of expression gradually increased up to 30 weeks for interleukin-6 (IL-6)
      precursor, transforming growth factor-beta (TGF-beta) induced protein, TIMP-1 and
      MMP-9. Cytochrome P450 2B, which is required for the metabolic activation of TAA,
      also showed the same increasing pattern. In contrast, the expression level of the
      proteins did not show a significant change at 9 weeks, but this increased to 3
      fold at 30 weeks for carbonic anhydrase VII, ras related protein Rab 6, Annexin
      A2, neurofibromatosis type 2 and aldehyde dehydrogenase. CONCLUSIONS: This study
      showed that there is a repertoire of proteins during the development of liver
      cirrhosis via TAA. In this model, IL-6, TGF-beta, MMP-9 and TIMP-1 were
      reconfirmed as the molecular signatures during the development of TAA-induced
      liver cirrhosis.

PMID- 16565611
TI  - [Toxic hepatitis associated with carp juice ingestion].
AB  - The potential hepatotoxicity of herbal remedies and/or health foods is usually
      ignored in daily life. There have been cases showing the toxic hepatitis and
      renal failure associated with the ingestion of raw carp bile. We experienced a
      case of toxic hepatitis without any evidence of renal failure that was associated
      with carp juice ingestion. The clinical manifestations were characterized by
      nausea and vomiting after the ingestion of carp juice for 3 months. The diagnosis
      of toxic hepatitis was made on the basis of the patient's history, laboratory
      data, RUCAM (Russel Uclaf Causality Assessment) and the results of
      ultrasonography guided liver biopsy. The patient showed rapid improvement after
      instituting supportive therapy.

PMID- 16565612
TI  - [A case of infiltrative hepatocellular carcinoma with main portal vein tumor
      thrombosis successfully treated by transarterial chemoembolization].
AB  - A 63-year-old HBsAg-positive male patient was admitted for the evaluation of a
      liver mass that was detected on ultrasonography. Spiral computed tomography (CT)
      revealed infiltrative hepatocellular carcinoma (HCC) in the right hepatic lobe
      with main portal vein tumor thrombosis. His liver function was Child-Pugh class A
      and the serum alpha fetoprotein level was 7,400 ng/mL. Transarterial
      chemoembolization (TACE) via the right hepatic artery was performed. Following 3
      sessions of TACE every 2 months, spiral CT revealed no evidence of viable tumor.
      The thrombi within the main portal vein disappeared with performing localized
      hepatic infarction at the site of the previous tumor. He is still alive 15 months
      after the third TACE without evidence of recurred tumor and his liver function
      remains well preserved. This case suggests that TACE might be effective and safe
      even in the patients with infiltrative HCC with main portal vein tumor
      thrombosis, if the extent of the tumor is limited and the liver function and
      portal flow via the collaterals are preserved.

PMID- 16565613
TI  - [Fatty liver].

PMID- 16565614
TI  - [Focal nodular hyperplasia of the liver: imaging findings with emphasis on the
      findings of superparamagnetic iron oxide-enhanced MR imaging].

PMID- 16565615
TI  - The effective management of pressure ulcers.
AB  - The challenges of managing pressure ulcers are often not limited to clinical
      decisions; they may impact other areas that encompass patient care, including
      financial, emotional, psychosocial, regulatory, and medical-legal aspects. The
      difficulty in managing these complex factors is magnified by recent gains in
      understanding of the pathophysiology of wounds related to pressure, which serves
      as the basis for the etiology, diagnosis, staging, and management of these
      wounds. This article summarizes the current and evolving knowledge related to
      pressure ulcers and discusses an algorithm recently developed to assist in
      clinical management decisions related to patients with pressure ulcers, with
      emphasis on appropriate utilization of Negative Pressure Wound Therapy delivered
      by V.A.C. Therapy (KCI USA, Inc.) in patients with Stage III and Stage IV
      pressure ulcers.

PMID- 16565617
TI  - Patterns of use of complementary therapies among cancer patients and their family
      caregivers.
AB  - Complementary therapies (CTs) are gaining popularity in the general population,
      including cancer patients, yet little is known about characteristics
      differentiating the use of one versus more CTs, about the patterns and
      persistence of CT use over time, or about the characteristics of cancer patients
      and their family caregivers who elect to participate in a study involving the use
      of CTs. The focus of this quasi-experimental study was to offer an 8-week, 5
      contact, nurse-delivered intervention involving guided imagery, reflexology, and
      reminiscence therapy to cancer patients undergoing chemotherapy and their family
      caregivers. Participants were allowed to elect to use none or any combination of
      CTs. Twenty-seven percent of eligible patients signed consent forms and agreed to
      participate. The typical participant was Caucasian, married, and had at least a
      high school education. Higher levels of education predicted use of more than 1 CT
      among cancer patients; there were no significant predictors for caregivers.
      Female patients were more likely to complete the CT protocol than their male
      counterparts, but there were no associations between CT protocol completion and
      caregiver demographics. Patients and family caregivers who elected to use more
      than 1 CT did not consistently implement their CTs. Participants who elected to
      use only 1 CT were more consistently performing their CT over time, suggesting
      that this lower level of CT use may be easier to integrate into their lives
      during cancer treatment.

PMID- 16565618
TI  - A brief behavioral sleep intervention for family caregivers of persons with
      cancer.
AB  - Behavioral interventions that support caregivers' restful sleep may delay the
      onset or decrease the severity of debilitating depressive symptoms. This, in
      turn, may increase caregivers' physical and psychological health and wellbeing. A
      repeated-measures experimental design was used to test the feasibility and
      effectiveness of a brief behavioral sleep intervention for family caregivers of
      persons with advanced stage cancer. The CAregiver Sleep Intervention (CASI)
      includes stimulus control, relaxation, cognitive therapy, and sleep hygiene
      elements. CASI is individualized and delivered to accommodate caregiver burden.
      Thirty adult caregivers participated. The Pittsburgh Sleep Quality Index (PSQI),
      Center for Epidemiological Studies-Depression scale (CES-D), and Caregiver
      Quality of Life-Cancer scale (CQOLC) were used to measure self-reported sleep
      quality, depressive symptoms, and quality of life. Actigraphs measured latency,
      duration, efficiency, and wake after sleep onset (WASO) scores. Data were
      collected at baseline, 3 and 5 weeks, 2, 3, and 4 months post baseline.
      Improvement was seen across groups; however, intervention caregivers showed more
      improvement in PSQI and CES-D scores than control caregivers. The CASI appears to
      be effective in improving sleep quality and depressive symptoms in caregivers of
      persons with cancer. Improvements in quality of life scores were similar across
      groups. Sample size and homogeneity limit generalizability.

PMID- 16565619
TI  - Quality of life in patients with advanced non-small cell lung cancer.
AB  - Quality of life (QOL) has been shown to improve with chemotherapy in patients
      with advanced non-small cell lung cancer (NSCLC), but the determinants of this
      improvement have not been thoroughly explored. Fifty consecutive NSCLC patients
      starting chemotherapy with measurable disease and with an Eastern Co-operative
      Oncology Group (ECOG) performance status of <or=2 were evaluated for change in
      QOL by European Organisation for Research and Treatment of Cancer Quality of Life
      Questionnaire (EORTC-QLQ-C30). The status of global QOL before chemotherapy
      influenced the degree of change in physical functioning (F = 8.71, P =.001),
      global QOL (F = 23.82, P <.001), and fatigue (F = 7.92, P =.001), whereas age of
      the patient was again linked with the change in global QOL (F = 4.68, P =.014),
      and type of chemotherapy administration (1st vs. 2nd line) was associated with
      the change in fatigue (F = 7.82, P =.001). Our findings show that patient age and
      baseline QOL assessed by EORTC-QLQ-C30, but not ECOG performance status, may help
      predict the amount of improvement in certain aspects of QOL in patients with
      advanced NSCLC undergoing chemotherapy. Conversely, in this cohort, patients who
      are likely to have deteriorating QOL on chemotherapy may benefit from closer
      follow-up and nursing care to optimize supportive measures.

PMID- 16565620
TI  - The relationship between meaning of illness, social support, coping strategies,
      and quality of life for lung cancer patients and their family members.
AB  - This article explores the relationship between meaning of illness, perceived
      social support resources, coping strategies used, and quality of life (QOL) by
      patients with lung cancer and their family members. The study was cross-sectional
      using interview data from 85 patients and associated family members. Regression
      results showed that total QOL in patients with lung cancer is predicted most by
      meaning of illness, specifically, the illness being perceived as manageable. QOL
      in family members is predicted most by meaning of illness, specifically, less
      adverse impact. Interestingly, the overall meaning of illness, coping strategies
      used, and social support were similar in the 2 groups. The results of the study
      emphasize the importance of acknowledging the circumstances of people's lives,
      both patients surviving lung cancer and their family members, which contribute to
      QOL.

PMID- 16565621
TI  - A population-based study of the quality of life of cancer survivors and their
      family caregivers.
AB  - Although survival rates for all cancers continue to increase, few studies have
      examined the quality of life of both cancer survivors and family caregivers
      during the survivorship period after treatment has ended. Information is lacking
      on the stressors, resources, meaning, and quality of life reported by survivors
      and family caregivers and the interrelationship between survivors' and family
      caregivers' quality of life. A stratified, random sample of 123 cancer survivors
      and 123 family caregivers (N = 246) were interviewed in an exploratory, cross
      sectional design 1-6 years after cancer treatment had ended. Approximately half
      (N = 62) of the dyads were white and half (N = 61) were African American. Results
      indicated that cancer survivors reported significantly higher quality of life,
      less fear of cancer recurrence, and more support than their family caregivers.
      The strongest predictors for cancer survivors' quality of life were family
      stressors, social support, meaning of the illness, and employment status, whereas
      the strongest predictors for family caregivers' quality of life were fear of
      recurrence and social support. Both the survivor's and family caregiver's quality
      of life independently contributed to the other's quality of life. Findings from
      this study suggest the importance of including both survivors and family
      caregivers in programs of care.

PMID- 16565623
TI  - Promoting community awareness of the need for colorectal cancer screening: a
      pilot study.
AB  - The purpose of this pilot study was to determine if a community education program
      based on the Health Belief Model effectively promotes awareness of the need for
      colorectal cancer (CRC) prevention and screening. An education program was given
      to 20 employees of an accounting firm in a midwestern city. A survey evaluated
      the participants' beliefs about CRC, before and after the presentation. The
      results support a significant increase in the belief that CRC is preventable, and
      in 5 of 6 screening factors from the Health Belief Model. Participants were
      encouraged to share what they learned and reported that they anticipate sharing
      with at least 31 others. A screening questionnaire was distributed as a "cue to
      action" to discuss CRC screening with their physicians. Participants' intention
      to discuss CRC with their physicians also increased. The actual effectiveness
      will be evaluated with 11 participants who volunteered for a 1-year follow-up
      study. This community education concept had several advantages, including
      simultaneous access to many participants who share personal testimonials and who
      invite peers to become screened. The program was effective in increasing
      awareness of the need for CRC prevention and screening, even beyond those in
      attendance. The results of the 1-year follow-up study may provide more insight to
      what education factors promote screening most effectively.

PMID- 16565624
TI  - Women's perceptions and beliefs about the genesis of their breast cancer.
AB  - A person's belief is seen as a set of assumptions, depending on perceptions, and
      formed with the influence of experiences and social culture. With the aim of
      understanding the beliefs about the genesis of their illness, 118 (59 + 59) women
      with different stages of breast cancer were interviewed. Half of the sample had
      chosen complementary care in an anthroposophical hospital, and the other half was
      a matched group. Qualitative content analysis was used. Three themes emerged: (1)
      belief in a link to life lived (71%), (2) heredity as the sole genesis (4%), and
      (3) rejection of the question (25%). Under beliefs in a link to life lived,
      external aspects to the patient's own life (eg, diet and lifestyle) were cited,
      as well as inner aspects such as psychosocial problems and stress. The findings
      show that women are well informed about medical facts, although their beliefs
      reveal a holistic approach. The women's beliefs, where inner psychosocial factors
      are uppermost, point to a reverse of the causal ranking of medical advisors. The
      difference between the groups was that the matching sample was more likely to
      reject the influence of possible causes from life lived. In a caring perspective,
      women's perceptions of the genesis of their illness are in some cases turned to
      creative health activities that may increase well-being.

PMID- 16565626
TI  - The influences of Chan-Chuang qi-gong therapy on complete blood cell counts in
      breast cancer patients treated with chemotherapy.
AB  - After surgery, breast cancer patients are offered adjuvant chemotherapy to avoid
      cancer cell spread. During chemotherapy process, neutrophils could fall
      relatively, and side effects could spike to the peak. Therefore, the medical care
      personnel should prevent the progression of the side effects. This study aimed to
      examine the effects of Chan-Chuang qi-gong therapy on complete blood counts in
      breast cancer patients treated with chemotherapy. This study used a quasi
      experimental design. The experiment group (n = 32) received a 21-day Chan-Chuang
      qi-gong therapy, whereas the control group (n = 35) did not. White blood cells,
      platelet, and hemoglobin were measured on the day before chemotherapy and on days
      8, 15, and 22 during chemotherapy. According to this study, there were
      significant differences in white blood cells (F = 115.76, P <.001), platelets (F
      = 25.29, P <.001), and hemoglobin (F = 15.39, P <.001) over the 3-week therapy
      between the experiment and control groups. Chan-Chuang qi-gong therapy may
      decrease leukopenia in breast cancer patients treated with chemotherapy. It is
      recommended conducting more studies on qi-gong and then introducing it in
      clinical nursing practice at an appropriate time to promote quality of nursing
      care and quality of patient life.

PMID- 16565627
TI  - Cardiopulmonary responses and adherence to exercise in women newly diagnosed with
      breast cancer undergoing adjuvant therapy.
AB  - Cardiopulmonary responses to an 8-week moderate-intensity aerobic exercise
      intervention and adherence to exercise during and after intervention were
      assessed in 41 women newly diagnosed with breast cancer undergoing adjuvant
      therapy. The intervention was primarily aimed at minimizing deconditioning. Women
      were randomly assigned to the intervention or control group, completed graded
      exercise tests before and after intervention, and encouraged to continue their
      exercise postintervention. Over time, only the intervention group showed
      significant decreases in resting heart rate, resting systolic blood pressure
      (SBP), P <.05 each, and maximum SBP, P <.02, and an increase in VO2 peak, P
      <.001, although resting SBP was higher in the intervention group at both
      timepoints, P <.05. The adherence rate to 8-week exercise intervention was 78.3%
      with average weekly attendance of 2.4 sessions and 42.7 minutes (27.8 minutes
      within target heart rate) exercise per session. Overall physical activity levels
      over 16 weeks postintervention did not differ between 2 groups. However, the
      within-group analysis indicated that only the intervention group showed a
      significant increase in voluntary activity, P < .02, and energy expenditure, P <
      .02, and a decrease in sedentary activity, P < .02. These findings indicate that
      moderate-intensity aerobic exercise is beneficial in reducing deconditioning of
      cardiopulmonary responses in newly diagnosed breast cancer women undergoing
      adjuvant therapy.

PMID- 16565628
TI  - Further challenges in adherence research: measurements, methodologies, and mental
      health care.

PMID- 16565630
TI  - The indirect costs of arthritis resulting from unemployment, reduced performance,
      and occupational changes while at work.
AB  - OBJECTIVE: The objective of this study was to assess the cost attributable to
      lost productivity from arthritis and the association between the degree of loss
      and demographic, disease-related, occupational, and psychosocial variables for
      people. METHODS: In a prospective study, 383 employed individuals with arthritis
      were recruited from southwestern Ontario, Canada. Respondents completed
      structured questionnaires assessing demographic, disease-related, workplace, and
      psychosocial variables as well as employment-related transitions at 2 time points
      18 months apart. Indirect costs resulting from arthritis-related absences,
      reduced performance, decreased work hours, job change, and work disability were
      estimated. A proportional odds model was used to assess the impact of the various
      variables on lost productivity. RESULTS: The average cost attributable to
      arthritis was CAN Dollars 11,553(Dollars CAN = 0.75 Dollars US) per person per
      year. The largest component of the loss was the result of reduced performance at
      work, which accounted for 41% (Dollars 4724) of the total loss. This was followed
      by wage loss resulting from stopping working or changing jobs, which comprised
      37% (Dollars 4309) of the total. Another 12% (Dollars 1398) and 10% (Dollars
      1121) of the loss were the result of the decrease in hours of work and
      absenteeism, respectively. Four variables were associated with the productivity
      loss: greater symptom severity (odds ratio [OR] = 1.11), low or medium control
      over the work schedule (OR = 0.55 and 0.60, respectively), greater workspace
      limitation (OR = 1.10), and higher depression (OR = 1.04). CONCLUSIONS: Indirect
      arthritis-related costs are substantial. Our results show that not only the
      disease itself, but also psychosocial and work-related factors affect the
      magnitude of the costs.

PMID- 16565629
TI  - Methods for evaluating patient adherence to antidepressant therapy: a real-world
      comparison of adherence and economic outcomes.
AB  - OBJECTIVE: The objective of this study was to differentiate between 3 measures of
      antidepressant adherence with regard to the number of patients deemed adherent to
      therapy and the association between adherence and resource utilization. DESIGN
      AND SETTING: The authors conducted a retrospective study of patients initiating
      selective serotonin reuptake inhibitor (SSRI) therapy for depression and/or
      anxiety between July 2001 and June 2002 in a large national managed care
      database. MAIN OUTCOME MEASURES: Rates of 6-month SSRI adherence were measured by
      3 different metrics: length of therapy (LOT), medication possession ratio (MPR),
      and combined MPR/LOT. Differences in resource utilization for each adherence
      metric were measured for patients deemed as 1) adherent, 2) nonadherent, 3)
      therapy changers, and 4) dose titraters. RESULTS: There were 22,947 patients
      meeting study criteria. Although statistically different, 6-month adherence rates
      were numerically similar across all methods (LOT, 44.6%; MPR, 43.3%; and MPR/LOT,
      42.9%, P < 0.001); approximately 57% of patients were nonadherent to therapy.
      Regardless of metric, the adherent cohort incurred the lowest yearly medical
      costs, followed by the nonadherent, titrate, and therapy change cohorts (P <
      0.001 between adherent cohort and all other cohorts). The LOT method produced the
      greatest difference in yearly medical costs between adherent and nonadherent
      patients (Dollars 511) followed by MPR/LOT (Dollars 432) and MPR (Dollars 423).
      When antidepressant prescription costs were added to medical costs, patients
      requiring a therapy change and titrating therapy incurred higher costs than
      adherent patients, whereas nonadherent and adherent patients incurred similar
      costs. CONCLUSION: Regardless of adherence metric, approximately 43% of patients
      were adherent to antidepressant therapy, and adherent patients were associated
      with the lowest yearly medical costs.

PMID- 16565631
TI  - Impact of changing the statistical methodology on hospital and surgeon ranking:
      the case of the New York State cardiac surgery report card.
AB  - BACKGROUND: Risk adjustment is central to the generation of health outcome report
      cards. It is unclear, however, whether risk adjustment should be based on
      standard logistic regression, fixed-effects or random-effects modeling.
      OBJECTIVE: The objective of this study was to determine how robust the New York
      State (NYS) Coronary Artery Bypass Graft (CABG) Surgery Report Card is to changes
      in the underlying statistical methodology. METHODS: Retrospective cohort study
      based on data from the NYS Cardiac Surgery Reporting System on all patient
      undergoing isolated CABG surgery in NYS and who were discharged between 1997 and
      1999 (51,750 patients). Using the same risk factors as in the NYS models, fixed
      effects and random-effects models were fitted to the NYS data. Quality outliers
      were identified using 1) the ratio of observed-to-expected mortality rates (O/E
      ratio) and confidence intervals (CIs) calculated using both parametric (Poisson
      distribution) and nonparametric (bootstrapping) techniques; and 2) shrinkage
      estimators. RESULTS: At the surgeon level, the standard logistic regression
      model, the fixed-effects model, and the fixed-effects component of the random
      effects model demonstrated near-perfect agreement on the identity of quality
      outliers using a quality indicator based on the O/E ratio and the Poisson
      distribution. Shrinkage estimators identified the fewest outliers, whereas the
      O/E ratios with bootstrap CI identified the greatest number of outliers. The
      results were similar for hospitals, except that the fixed-effects model
      identified more outliers than either the NYS model or the fixed-effects component
      of the random-effects model. CONCLUSION: Shrinkage estimators based on random
      effects models are slightly more conservative in identifying quality outliers
      compared with the traditional approach based on fixed-effects modeling and
      standard regression. Explicitly modeling surgeon provider effect (fixed-effects
      and random-effects models) did not significantly alter the distribution of
      quality outliers when compared with standard logistic regression (which does not
      model provider effect). Compared with the standard parametric approach, the use
      of a bootstrap approach to construct 95% confidence interval around the O/E ratio
      resulted in more providers being identified as quality outliers.

PMID- 16565632
TI  - Examination of the effects of financial risk on the formal treatment costs for a
      Medicaid population with psychiatric disabilities.
AB  - OBJECTIVES: We examined the effects of differing financial risk arrangements for
      mental health, physical health, and pharmacy services on the overall costs of
      these services with particular attention to cost containment and cost shifting.
      METHODS: Comprehensive service utilization information was obtained from a sample
      of 458 adults with severe mental illnesses during a 12-month period. Rate
      information was used to calculate costs for health, mental health and pharmacy. A
      2-part model was employed to test for differences among financial risk
      conditions. RESULTS: Total treatment costs, both those financed by Medicaid and
      those paid by other sources, were lower in plans that had a broader array of
      services for which they were at risk. Pharmacy costs were principally responsible
      for these differences. CONCLUSIONS: Treatment costs for adults with severe mental
      illnesses can be contained by placing providers at financial risk. However, risk
      arrangements may also increase treatment costs borne by other payers including
      charity services and self-pay. Evaluating the impact of at-risk financing
      mechanisms from a public health perspective requires assessing cost shifting,
      particularly for pharmaceuticals.

PMID- 16565633
TI  - Development and validation of a surname list to define Chinese ethnicity.
AB  - OBJECTIVE: Surnames have the potential to accurately identify ancestral origins
      as they are passed on from generation to generation. In this study, we developed
      and validated a Chinese surname list to define Chinese ethnicity. METHODS: We
      conducted a literature review, a panel review, and a telephone survey in a
      randomly selected sample from a Canadian city in 2003 to develop a Chinese
      surname list. The list was then validated to data from the Canadian Community
      Health Survey. Both surveys collected information on self-reported ethnicity and
      surname. RESULTS: Of the 112,452 people analyzed in the Canadian Community Health
      Survey, 1.6% were self-reported as Chinese. This was similar to the 1.5%
      identified by the surname list. Compared with self-reported Chinese ethnicity
      (reference standard), the surname list had 77.7% sensitivity, 80.5% positive
      predictive value, 99.7% specificity, and 99.6% negative predictive value. When
      stratifying by sex and marital status, the positive predictive value was 78.9%
      for married women and 83.6% for never married women. CONCLUSIONS: The Chinese
      surname list appears to be valid in identifying Chinese ethnicity. The validity
      may depend on the geographic origins and Chinese dialects in given populations.

PMID- 16565634
TI  - Randomized trial of onsite versus referral primary medical care for veterans in
      addictions treatment.
AB  - BACKGROUND: Patients presenting for treatment of substance use disorders (SUDs)
      often exhibit medical comorbidities that affect functional health status and
      healthcare costs. Providing primary care within addictions clinics (onsite care)
      may improve medical and SUD treatment outcomes in this population. OBJECTIVE: The
      objective of this study was to compare outcomes among Veterans' Administration
      (VA) patients who receive medical care within the SUD clinic and those referred
      to a general medicine clinic at the same facility. METHODS: Veterans entering SUD
      treatment with a chronic medical condition and no current primary care were
      randomized to receive primary medical care: 1) onsite in the VA SUD clinic (n =
      358), or 2) in the VA general internal medicine clinic (n = 362). Subjects were
      assessed at baseline and at 3, 6, and 12 months postrandomization. Intention-to
      treat analyses used random-effects regression. MEASURES: Measures included SF-36
      Physical and Mental Component Summaries (PCS, MCS), VA service utilization, SUD
      treatment retention, Addiction Severity Index (ASI) scores, 30-day abstinence,
      and total VA healthcare costs. RESULTS: Over the study year, patients assigned to
      onsite care were more likely to attend primary care (adjusted odds ratio [OR] =
      2.20; 95% confidence interval [CI] = 1.53-3.15) and to remain engaged in SUD
      treatment at 3 months (adjusted OR = 1.36; 1.00-1.84). Overall, outcomes on the
      MCS (but not the PCS) and the ASI improved significantly over time but did not
      differ by treatment condition. Total VA healthcare costs did not differ reliably
      across conditions. CONCLUSIONS: Compared with referral care, providing primary
      care within a VA addiction clinic increased primary care access and initial SUD
      treatment retention but showed no effect on overall health status or costs.

PMID- 16565635
TI  - Risk of nursing home admission in association with mental illness nationally in
      the Department of Veterans Affairs.
AB  - OBJECTIVE: We sought to determine whether patients with mental health diagnoses
      in the Department of Veterans Affairs (VA) are more likely to be admitted to
      nursing homes and to identify sociodemographic, utilization, and clinical
      characteristics, especially indicators of mental illness severity, associated
      with nursing home admission among mentally ill patients. METHODS: Patients
      receiving treatment in the VA system nationally during FY 2000 and having no
      evidence of nursing home utilization during FY 1999 or FY 2000 were followed
      through FY 2003 using administrative claims data. Three-year incidence rates and
      unadjusted odds ratios were estimated for each diagnosis. Logistic regression was
      used to examine the correlates of admission among mentally patients, including
      analyses stratified by age. RESULTS: Of 3,952,229 VA patients with no prior
      nursing home use, 15.2% received a mental health diagnosis, of which, 4.6% were
      eventually admitted to a nursing home. Among mentally ill patients, risk of
      admission was highest for those with any inpatient medical/surgical days (odds
      ratio [OR] = 2.28), followed by 3+ outpatient medical visits (OR = 1.48),
      inpatient mental health days (OR = 1.31), and outpatient mental health visits (OR
      = 1.09). Patients diagnosed with dementia were 58% more likely to be admitted.
      Patients diagnosed schizophrenia (OR = 1.26), other psychosis (OR = 1.15), and
      personality disorder (OR = 1.14) had the next highest probabilities. Elderly
      patients with bipolar disorder (OR = 1.28) were also more likely to enter.
      CONCLUSION: Although factors leading to nursing home entry among the mentally ill
      are similar to those driving entry in the general population, those with more
      severe mental health problems are still more likely to be admitted.

PMID- 16565636
TI  - Modeling the impact of enhanced depression treatment on workplace functioning and
      costs: a cost-benefit approach.
AB  - BACKGROUND: The impact of depression on the workplace has been widely observed in
      studies examining absenteeism and reduced productivity during days at work.
      However, there is little scientific evidence about whether depression
      interventions are cost-beneficial to employers. OBJECTIVE: We construct a cost
      benefit analysis of depression treatment under different workplace assumptions
      better reflecting the nature of employment. RESEARCH DESIGN: Data from a
      randomized controlled trial in which employed primary care patients with
      depression were treated in practices randomly assigned to an enhanced treatment
      intervention or usual care were used to construct a cost-benefit model from an
      employer perspective under different assumptions regarding employment. SUBJECTS:
      A national sample of 198 workers employed in a range of positions by companies
      was studied. MEASURES: Benefits included self-reported productivity and
      absenteeism; costs included intervention and treatment costs. Net benefit was
      calculated under different scenarios and return on investment (ROI) is derived.
      RESULTS: Enhanced depression treatment resulted in an average net benefit to the
      employer of Dollars 30 per participating worker in Year 1 of the intervention and
      Dollars 257 per participating worker in Year 2, for an estimated ROI during the 2
      year period of 302%. ROI increased in firms that rely on team production, hire
      more costly substitute labor, or realize penalties for output shortfalls. ROI
      decreased in firms that have a large fraction of employees with dependent
      coverage and experience high turnover rates. Results also are sensitive to how
      subjectively reported productivity is valued. CONCLUSION: Many employers will
      receive a potentially significant ROI from depression treatment models that
      improve absenteeism and productivity at work.

PMID- 16565637
TI  - Risk-adjusted mortality as an indicator of outcomes: comparison of the Medicare
      Advantage Program with the Veterans' Health Administration.
AB  - BACKGROUND: The Medicare Advantage Program (MAP) and the Veterans' Health
      Administration (VHA) currently provide many services that benefit the elderly,
      and a comparative study of their risk-adjusted mortality rates has the potential
      to provide important information regarding these 2 systems of care. OBJECTIVE:
      The objective of this retrospective study was to compare mortality rates between
      the MAP and the VHA after controlling for case-mix differences. SUBJECTS: This
      study consisted of 584,294 MAP patients and 420,514 VHA patients. MEASURES: We
      used the Death Master File to ascertain the vital status of each study subject
      over approximately 4 years. We used Cox regression models to estimate hazard
      ratios (HRs) with 95% confidence intervals (CIs) for the MAP compared with VHA
      patients. RESULTS: The average age for male MAP patients was 73.8 years (+/- 5.6)
      and for male VHA patients was 74.05 years (+/- 6.3). Unadjusted mortality rates
      of males for VHA and MAP were 25.7% and 22.8%, respectively, over approximately 4
      years (P < 0.0001), respectively. The case-mix of VHA patients, however, was
      sicker than those from MAP. After adjusting for case-mix, the HR for mortality in
      the MAP was significantly higher than that in the VHA (HR, 1.404; 95% CI = 1.383
      1.426). We obtained similar results when we compared the mortality rates of
      females for VHA and MAP. CONCLUSIONS: After adjusting for their higher prevalence
      of chronic disease and worse self-reported health, mortality rates were lower for
      patients cared for in the VHA compared with those in the MAP. Further studies
      should examine what differences in care structures and processes contribute to
      lower mortality in the VHA.

PMID- 16565638
TI  - Expanded mental health benefits and outpatient depression treatment intensity.
AB  - BACKGROUND: The justification for higher cost-sharing for behavioral health
      treatment is its greater price sensitivity relative to general healthcare
      treatment. Despite this, recent policy efforts have focused on improving access
      to behavioral health treatment. OBJECTIVES: We measured the effects on outpatient
      treatment of depression of a change in mental health benefits for employees of a
      large U.S.-based corporation. RESEARCH DESIGN: The benefit change involved 3
      major elements: reduced copayments for mental health treatment, the
      implementation of a selective contracting network, and an effort to destigmatize
      mental illness. Claims data and a difference-in-differences methodology were used
      to examine how the benefit change affected outpatient treatment of depression.
      SUBJECTS: Subjects consisted of 214,517 employee-years of data for individuals
      who were continuously enrolled for at least 1 full year at the intervention
      company and 96,365 employee-years in the control group. MEASURES: We measured
      initiation into treatment of depression and the number of outpatient therapy
      visits. RESULTS: The benefit change was associated with a 26% increase in the
      probability of initiating depression treatment. Conditional on initiating
      treatment, patients in the intervention company received 1.2 additional (P <
      0.001) outpatient mental health treatment visits relative to the control group.
      CONCLUSIONS: Our results suggest that the overall effect of the company's benefit
      change was to significantly increase the number of outpatient visits per episode
      of treatment conditional on treatment initiation.

PMID- 16565639
TI  - Implications of new geriatric diabetes care guidelines for the assessment of
      quality of care in older patients.
AB  - BACKGROUND: Current approaches to assessing quality of diabetes care do not
      account for the heterogeneity of older patients. OBJECTIVE: We sought to compare
      conclusions regarding adequacy of glucose and blood pressure control using
      current quality assessment approaches and a stratified approach based on
      geriatric care guidelines. DESIGN: This was a cross-sectional evaluation of
      diabetes care. SUBJECTS: We studied patients older than 65, living with diabetes
      (n = 554) attending clinics of an academic medical center. MEASUREMENTS: We
      measured the proportion of patients with and without markers of poor health (life
      expectancy < or = 5 years, age > or = 85, 4-6 activities of daily living
      dependencies, or Charlson Comorbidity Index Score > or = 5) achieving treatment
      goals. RESULTS: Under general population goals (glycosylated hemoglobin [HbA1C] <
      or = 6.5% or < 7%; systolic blood pressure [SBP] < 130 mm Hg), a small proportion
      of our subjects met glucose (24-36%) or SBP control (30%) targets. Under new
      guidelines, less-intense targets (HbA1C < or = 8%, SBP < 140 mm Hg) would be
      applied to patients with diminished health, with general population goals
      reserved for healthier patients. With this stratified approach, the proportion of
      sicker patients achieving their specified glucose (61-83%) and SBP goals (37-64%)
      generally was high, depending on the criteria for poor health, whereas the
      proportion of healthier patients achieving their goals remained low. CONCLUSIONS:
      A stratified approach to assessing the quality of diabetes care leads to distinct
      care conclusions for older patients with and without markers of diminished
      health. An approach to quality assessment and quality improvement that
      acknowledges patient heterogeneity could help ensure the clinical relevance of
      such efforts for older patients.

PMID- 16565640
TI  - Differential effect of early or late implementation of prior authorization
      policies on the use of Cox II inhibitors.
AB  - BACKGROUND: State Medicaid programs introduce many types of prescribing
      restrictions to manage pharmaceutical use and expenditure. Little is known about
      the differential effect of implementing prior authorization (PA) policies at
      market entry versus waiting until several years later when prescribing behavior
      may already be established. OBJECTIVES: We sought to examine the impact on
      overall use of Cox II inhibitors of PA policies implemented at market entry
      versus at least 2 years after market entry. RESEARCH DESIGN: We quantified Cox II
      inhibitor and nonselective nonsteroidal anti-inflammatory drug (NSAID)
      utilization for state Medicaid programs from January 1996 to September 2003. We
      used generalized estimating equations, Tukey's studentized range test and
      segmented linear regression on state Medicaid programs to determine the
      significance of changes in medication use. MEASURES: The primary end point was
      the number of defined daily doses (DDD) per 1000 population per day. RESULTS: Six
      states implementing prescribing restrictions for Cox II inhibitors at market
      entry had the lowest rates of uptake, averaging 10.9 DDD/1000/d. Twelve states
      adopting restrictions more than 2 years after market entry experienced declines
      in use from 23.0 DDD/1000/d before to 13.9 DDD/1000/d after the restrictions (P <
      0.01). The 17 states that had never restricted access had the highest
      utilization, averaging 29.0 DDD/1000/d. CONCLUSION: Implementing prescribing
      restrictions at market entry of Cox II inhibitors was effective in restricting
      uptake. Despite the difficulty in changing well-established prescribing patterns,
      utilization in states implementing policies 2 years after market entry approached
      that of the early adopting states within 1 year. Clinical outcomes of such
      policies remain unknown.

PMID- 16565641
TI  - Perceptions of the influence of prescription medicine samples on prescribing by
      family physicians.
AB  - BACKGROUND: The provision of free prescription medicine samples is a common and
      traditional marketing strategy used by pharmaceutical companies, but concerns
      have been raised about their influence on physician prescribing behavior and
      patient safety. OBJECTIVE: We sought to investigate the knowledge, attitudes, and
      behaviors of Australian family physicians regarding the use of sample
      prescription medications. METHODS: Qualitative and quantitative techniques were
      used, including (1) mailed questionnaires to family physicians, (2)
      semistructured interviews with family physicians, and (3) sample cupboard
      inventories. RESULTS: A number of issues about samples were identified by the
      questionnaires (208) and interviews (17 doctors), including insufficient
      labeling, poor record keeping, diversion of stock (personal use by doctors, their
      families, practice staff and pharmaceutical representatives), and wasting of
      expired stock. Prescription medicine samples also influenced prescribing
      behavior. Australian doctors were less likely to provide samples to patients on
      financial grounds compared with a previous study in the United States on medical
      residents. Six sample cupboards were inventoried. Median wholesale value of
      sample cupboards was AUD Dollars 4959 (range Dollars 2395-Dollars 8709), with 6%
      of stock expired. Very little generic medicine was included in the sample
      cupboards. CONCLUSIONS: Better methods are needed to meet legislative
      requirements and to ensure quality use of medicines (and optimal public health)
      with respect to prescription medicine samples. Doctors and practice staff require
      training on the appropriate handling and storage of prescription medications.
      Alternative ways for distribution of sample medications need to be investigated.

PMID- 16565642
TI  - Vaginal douche practices among black women at risk: exploring douching
      prevalence, reasons for douching, and sexually transmitted disease infection.
AB  - OBJECTIVE: The objective of this study was to identify douching patterns and
      their relation to sexually transmitted disease (STD) among black women seeking an
      STD evaluation. STUDY DESIGN: This study was a cross-sectional survey with
      biologic testing for chlamydia and gonorrhea infection. RESULTS: Of 891
      participants, 46.1% were current douchers. Commonly identified reasons for
      douching were to cleanse after menses (65.4%) and to feel fresh (42.2%). Frequent
      douching was associated with douching after sex (P<0.001), to alleviate an itch
      (P<0.001), and to feel fresh (P<0.001). Women who douched during menses (adjusted
      odds ratio [AOR]=4.78; 95% confidence interval [CI]=1.13-20.13) and to alleviate
      an itch (AOR=3.66; 95% CI=1.00-13.41) were more likely to have a current
      chlamydial infection. CONCLUSIONS: Douching was common among this high-risk
      population of black women. Prospective studies are needed to determine the
      consequences of douching and any mediating effects of women's motivation for the
      behavior on reproductive health.

PMID- 16565643
TI  - Commercial sex work and risk of HIV infection among young drug-injecting men who
      have sex with men in San Francisco.
AB  - OBJECTIVE: The objective of this study was to investigate the relationship
      between sex work and HIV infection among young injection drug-using men who have
      sex with men (MSM-IDU). STUDY DESIGN: This study was a cross-sectional analysis
      of behavioral and serologic data collected from 227 street-recruited MSM-IDU in
      San Francisco, California, between January 2000 and November 2001. RESULTS: Sixty
      eight percent of participants reported being paid by another man for sex. HIV
      prevalence was 12% (95% confidence interval, 8-16%); 42% of seropositive
      participants were unaware of their infection. HIV was independently associated
      with higher number of paying male partners and history of gonorrhea and inversely
      associated with number of female partners, education, and syringe-sharing.
      Consistent condom use overall was 41%, but varied significantly by type of
      partner. CONCLUSIONS: Among MSM-IDU in San Francisco, sex work with men is
      strongly associated with HIV infection and the prevalence of condom use is low.
      HIV prevention among MSM-IDU must be tailored to address the excess risk
      associated with sex work.

PMID- 16565644
TI  - Evaluation of clinician-reported adherence to Centers for Disease Control and
      Prevention guidelines for the treatment of Chlamydia trachomatis in two U.S.
      health plans.
AB  - OBJECTIVE: The objective of this study was to assess clinician adherence to
      Centers for Disease Control and Prevention-recommended treatments for Chlamydia
      trachomatis (CT) in two health plans. STUDY DESIGN: Using hypothetical scenarios,
      a 1999-2000 mail survey questioned clinicians about how they would treat a
      cervicitis patient (CT and gonorrhea treatment recommended) and two patients with
      laboratory-confirmed CT: an injection drug user (single-dose azithromycin
      promotes adherence) and a pregnant patient (nonteratogenic drugs recommended).
      RESULTS: Seven hundred forty-three (82%) of the 907 nonretired clinicians
      receiving the survey completed it. Eighty-one percent (N=599) reported providing
      recent CT care. Of these, 70.1% reported they would presumptively treat patients
      with cervicitis for CT and gonorrhea, 17.1% for CT only, and 11.7% for neither
      pathogen. Of the 580 clinicians addressing drug injectors, 61.7% reported they
      would prescribe azithromycin. Most (88.8%) of the 343 clinicians seeing pregnant
      patients reported they would prescribe Centers for Disease Control and Prevention
      (CDC)-recommended antibiotics. Reported adherence varied by clinician specialty
      and sources of treatment guidance. CONCLUSIONS: Most clinicians reported
      treatment consistent with CDC guidelines.

PMID- 16565645
TI  - Syphilis management in St. Petersburg, Russia: 1995-2001.
AB  - OBJECTIVES: The objectives of this study were to describe the recent syphilis
      epidemic in St. Petersburg, Russia; and to document the syphilis management
      practices in Russia to help inform the best way forward for a system in
      transition. DESIGN: This study was a retrospective cohort study of syphilis
      diagnosed and followed in St. Petersburg, 1995-2001. RESULTS: A total of 1,024
      persons were identified with syphilis. Persons treated for secondary syphilis
      with 400,000 IU aqueous penicillin intramuscularly every 3 hours for 28 days or
      2.4 micro benzathine penicillin intramuscularly weekly for 2 weeks responded most
      rapidly. Persons treated with 1.5 micro bicillin-5 intramuscularly at diagnosis
      and then two times per week for 3 weeks or 2.4 micro bicillin-1 intramuscularly
      weekly for 3 weeks displayed sluggish responses (P<0.0001). Regimens for treating
      later stages revealed similar responses (P=0.21). Benzathine penicillin at a
      dosage of 2.4 micro intramuscularly weekly for 3 weeks was not a used regimen.
      CONCLUSION: Benzathine penicillin at a dosage of 2.4 mu intramuscularly weekly
      for 1 to 2 weeks is in moderate use but its use should increase; 2.4 mu
      benzathine penicillin intramuscularly weekly for 3 weeks should be introduced as
      the standard of care for late syphilis. The efficacy of the locally manufactured
      bicillin-1 and bicillin-5 is in question.

PMID- 16565646
TI  - Evaluation of the new National HIV Behavioral Surveillance System (NHBS) is
      imperative.

PMID- 16565648
TI  - Medical community preferences concerning adult living related donor liver
      transplantation.
AB  - OBJECTIVES: To assess acceptance and acceptable estimated mortality levels for
      right lobe adult-to-adult living related liver transplantation for the medical
      and allied professions. METHODS: A paper questionnaire was sent to the physicians
      practicing with the French Graft Agency (Etablissement Francais des Greffes) and
      to all nurses and ancillary staff of the Paul Brousse Hospital Hepatobiliary
      Center. Responses were received from surgeons: 38/73; internists specialized in
      hepatology: 44/120; nurses: 98/100; health care assistants: 45/86; others: 17/20.
      RESULTS: Acceptance of living donor transplantation is above average for all
      professional categories and indications may be extended including patients with
      cancer. Acceptable mortality for the donor was 4%, except among internists
      (0.7%). Currently, the real risk of mortality for the donor (1%) is lower.
      Acceptable mortality for the recipient was between 15 and 20%. CONCLUSIONS:
      Acceptance of adult living donor liver transplantation among health care
      professionals is clearly above average. Thus the psychological involvement of
      transplantation teams, which is very strong in such situations, should not hamper
      the development of this type of transplantation.

PMID- 16565650
TI  - Hepatitis B vaccination in HIV-infected patients: a survey of physicians and
      patients participating in the Aquitaine cohort.
AB  - In France, HIV-infected (HIV+) patients are frequently coinfected with hepatitis
      B virus (HBV) or at risk for this infection. Physicians and their patients should
      be more committed to HBV prevention than the average population. AIMS: To gain
      insight into the attitude towards HBV and its vaccination in HIV+ patients from
      the Aquitaine Cohort and their attending physicians in France. METHODS: A cross
      sectional survey based on self-administered questionnaires was performed from
      November 2002 to June 2003. It targeted 198 physicians from the clinical group on
      AIDS epidemiology (Groupe d'Epidemiologie Clinique du SIDA en Aquitaine, GECSA)
      or participating in medical HIV networks in southwestern France; and 512 patients
      from the cohort. Questions concerned the following items for the physicians: HBV
      status, prescription of HBV serology and vaccination (frequency, type, schedule),
      risk factors assessed, reasons for non-vaccination; and for the patients: HBV
      status, information received, risk factors, attitude towards vaccination.
      RESULTS: 93% of physicians and 22% of patients stated they were vaccinated
      against HBV. HBV serological status was reported to be systematically ascertained
      by 75% of physicians, but post-vaccinal testing was only prescribed by 23% of
      them. The main reasons for not prescribing more often HBV vaccine were forgetting
      (79%), difficulty to identify subjects at risk (44%) and being afraid of post
      vaccinal complications (32%). Thirty percent of patients reported not to have
      received any information on HBV vaccination. Overall, 44% considered not to be at
      risk of infection but 82% of them had been confronted with at least one risk. The
      main reasons for not having been vaccinated were mostly worry about AIDS (70%),
      not having been asked by physician (65%) or afraid of complications (58%);
      nonetheless, 42% of patients were willing to be vaccinated. CONCLUSIONS: Results
      from this survey underline the need for specific health actions to be undertaken
      concerning hepatitis B vaccination in HIV+ patients as well as their health care
      providers.

PMID- 16565651
TI  - [Complementary treatments of chronic viral hepatitis C].
AB  - Pegylated interferon and ribavirin combination therapy represent the standard-of
      care treatment for chronic hepatitis C, that allows to cure more than half of the
      patients. However, the success of this bitherapy is in balance with numerous side
      effects, especially hematologic and psychiatric. This review is focused on
      complementary treatments (erythropoietin, G-CSF, vitamin E, glutathion,
      ursodeoxycholic acid and antidepressants) likely to bring a benefit in
      maintaining adequate interferon and ribavirin dosages and in improving quality of
      life. This analysis has been performed by using the Medline(R) data base and with
      data from laboratories which commercialized these molecules. Erythropoietin, G
      CSF and antidepressants are the best tools to optimize the bitherapy in its dose
      and its duration while privileging the quality of life of HCV-infected patients.

PMID- 16565652
TI  - [Crohn's disease: nutrition should not be forgotten].

PMID- 16565653
TI  - Diagnostic accuracy of magnifying chromoendoscopy with detection of intestinal
      metaplasia and dysplasia using acetic acid in Barrett's esophagus.
AB  - OBJECTIVES: Endoscopy with systematic randomized biopsies aims to improve the
      detection of intestinal metaplasia (IM) and dysplasia in Barrett's esophagus
      (BE). Magnifying chromoendoscopy with alcoholic acetic acid might allow directed
      biopsies to improve detection of IM and dysplasia. PATIENTS AND METHODS: Twenty
      eight patients were studied with magnifying chromoendoscopy (Optical power zoom x
      115, alcoholic acetic acid). Endoscopy biopsies were performed on one or several
      zones of BE chosen randomly, for which the chromoendoscopic pattern was
      determined according to Guelrud's classification. RESULTS: Among seventy-two
      biopsies, the agreement between magnifying chromoendoscopy and histology and the
      positive predictive value of the association of patterns III and IV for the
      diagnosis of IM were 72.4%; sensibility and specificity were respectively 95.5%
      and 42.9%. The diagnostic accuracy was 75%. Among the six biopsies that showed
      high-grade dysplasia, three were suspected because of two particular patterns:
      local loss of ridged cerebriform pattern due to the disorganization of the
      mucosal folds and hypervascularization of the mucosa. CONCLUSION: Magnifying
      chromoendoscopy with acetic acid allows targeted biopsies of the IM in BE and may
      help to detect high-grade dysplasia.

PMID- 16565654
TI  - Subsequent resection of locally advanced pancreatic carcinoma after
      chemoradiotherapy.
AB  - OBJECTIVES: The aim of this study was to evaluate the possibility of subsequent
      resection of locally advanced pancreatic adenocarcinoma after chemotherapy and
      external-beam radiotherapy. PATIENTS AND METHODS: Between January 1996 and
      January 2001, 33 consecutive patients (18 males and 15 women, mean age 63 years)
      with locally advanced PA were treated with chemotherapy and concurrent external
      beam radiotherapy. Radiotherapy delivered 45-50.4 Gy, in a classical manner
      (N=27) or on a split-course (N=6). Chemotherapy was made of 5FU by continuous
      infusion for all patients during 5 weeks and cisplatin at the 1st and 5th weeks
      (N=22). Tumor resectability was reassessed at the end of the chemoradiotherapy;
      surgical resection of tumour was attempted in patients whose tumor demonstrated
      reduction in size, and supplementary radiotherapy of 10 to 15 Gy was delivered to
      the others. RESULTS: Thirty-nine percent of patients experienced grade 3 acute
      toxicity. WHO criteria response to chemoradiotherapy four weeks after the end of
      treatment were: 4 partial responders (12%), 6 minor responders (18%), 14 stable
      disease (42%), 9 progression (28%). Ten patients underwent exploratory
      laparotomy, in one case vascular encasement did not allow for tumor resection,
      and in another patient, there was peritoneal carcinomatosis. In the 8 remaining
      patients, surgical (R0) resection was possible. In one patient histological
      examination showed fibrosis with no residual tumour. After a median follow-up
      period of 40 months, median survival was 16 months (66% and 37% of survival at 1
      and 2 years respectively). In operated and non-operated patients, survival rates
      at 24 months were 73% and 12.5% respectively. At 1 year, 80% of the patients
      treated with radiochemotherapy developed recurrence, metastatic recurrence in
      88%. Initial laparotomy, split course radiotherapy were poor outcome factors
      whereas chemotherapy appears to be a favorable outcome factor. CONCLUSION:
      Subsequent resection of locally advanced pancreatic adenocarcinoma is possible
      after chemoradiotherapy allowing for a prolonged survival in some patients.

PMID- 16565655
TI  - Water enema computed tomography: diagnostic tool in suspicion of colorectal
      tumor.
AB  - OBJECTIVES: The aim of this study was to assess the accuracy of water enema multi
      row computed tomography for detecting clinically suspected colorectal tumor.
      PATIENTS AND METHODS: A water enema multi-row computed tomography (WE-MR-CT) was
      performed in 128 consecutive patients (71 women, mean age 67.7 years) referred
      for suspicion of colorectal cancer. We defined at least one centimeter size of
      the lesion as the threshold of detection. The results of WE-MR-CT were compared
      with the diagnosis obtained by colonoscopy, pathology or clinical follow-up.
      RESULTS: The overall sensitivity and specificity of water enema multi-row CT in
      identifying patients with colorectal lesions were 95.5% and 93.5%, respectively.
      The negative predictive value was 98.8% for a 10-mm threshold lesion size. WE-MR
      CT allowed identifying synchronous lesions in three cases. CONCLUSIONS: WE-MR-CT
      can accurately detect supracentimetric colorectal tumors. The performance of this
      technique should be further evaluated in prospective studies.

PMID- 16565656
TI  - Quality and completeness of histopathology reports of rectal cancer resections.
      Results of an audit in Brittany.
AB  - Few data are available in France about implementation of guidelines for pathology
      reports of rectal cancer resections. AIM: The purpose of this study was to audit
      quality and completeness of histopathology reports of rectal cancer resections in
      Brittany by comparing results with French guidelines published in 1998. METHODS:
      All inhabitants in Brittany who were beneficiaries of the general health
      insurance system and who underwent surgery for rectal cancer between February
      1999 and January 2000 were included in the study. Twenty-one pathology
      laboratories, including 14 private laboratories, participated in this study. All
      pathology reports were examined by two physician-consultants of the health
      insurance system trained in the analysis of pathology reports (search for
      consigned or missing data). Results were compared with guidelines published in
      1998. RESULTS: Of 234 pathology reports, 204 (84%) mentioned the number of
      examined lymph nodes and 217 (93%) the number of those found positive. The
      criterion of at least 8 examined lymph nodes was noted in 53.4% of reports.
      Longitudinal margin involvement was recorded in 92% of reports and
      circumferential margin involvement in 27% only. Venous and/or lymphatic and
      neural invasion were recorded in 34% and 18% of reports, respectively. Tumor
      staging was made by using UICC (pTNM) in 67% of reports. CONCLUSION: This study
      shows that the quality and completeness of histopathology reports of rectal
      cancer resections could be improved in Brittany. Despite its documented value as
      an important predictor of local recurrence, circumferential margin involvement is
      too frequently omitted. Standardisation of the examination procedures and
      exhaustive reporting would be useful to improve practice quality.

PMID- 16565657
TI  - Impact of irritable bowel syndrome (IBS) on health-related quality of life
      (HRQOL).
AB  - AIMS: To assess the impact of irritable bowel syndrome (IBS) on patient-reported
      health-related quality of life (HRQOL). METHODS: Two HRQOL instruments were
      administered by telephone interviews to a sample of 253 IBS French patients
      recruited from the general population. IBS was diagnosed according to the
      Manning, Rome I and Rome II criteria. Patients with organic diseases were
      excluded from the study. A generic instrument, the Short Form 36 (SF-36), and an
      IBS disease-specific instrument, the IBSQOL, were used. RESULTS: Patients with
      IBS had statistically significant (P<0.05) lower scores for all SF-36 QOL domains
      compared with the general French population. Women (N=192) reported significantly
      (P<0.05) poorer HRQOL on both the SF-36 and the IBSQOL scores than men (N=61) for
      all domains except energy on the SF36 and the sleep on the IBSQOL. HRQOL
      deteriorated with time since onset of IBS symptoms for some domains such as diet.
      For both instruments, a positive correlation was observed between low scores and
      intensity of pain and discomfort. IBS patients with a predominance of diarrhea
      (N=72) exhibited significantly greater impairment of HRQOL in the emotional
      domain than IBS persons with constipation predominance (N=65) (P<or=0.05).
      CONCLUSION: IBS has a significant impact on HRQOL of patients. In addition,
      specific characteristics such as gender, symptom severity and time since onset of
      symptoms are predictive of more impaired health-related quality of life.

PMID- 16565659
TI  - [Palliative endoscopic treatments for esophageal cancers].
AB  - Esophageal cancer five-year survival has slightly increased during past 20 years
      (from 5 to 9%), but remains low. At time of diagnosis, 60% of the patients are
      only relevant for palliative therapy. Recent advances in therapeutic endoscopy
      have allowed improving dysphagia and quality of life. Endoscopic techniques are
      chosen according to tumor characteristics. According to French societies
      guidelines (FFCD, "Standards-Options-Recommandations" from FNCLCC, SNFGE)
      endoscopic treatment is a "gold standard" for metastatic patients with poor
      performance status, as well as oesophago-tracheal fistula. Expandable metal stent
      are efficient for malignant stenosis with lower morbidity and mortality than
      plastic prosthesis. Endoscopic placement of a covered self-expanding metal stent
      is the treatment of choice of an esophago-respiratory fistula. Dilatation is
      often the first step before other endoscopic therapies or medical treatment such
      as radiochemotherapy. Single dose brachytherapy could provide better long-term
      relief of dysphagia and fewer complications than stent placement, but is less
      widespread. Other techniques like bipolar electrocoagulation have restricted
      indications especially for circonferential stenosis of cervical esophagus.
      However, the main problem remains the dysphagia relapse after treatment.

PMID- 16565658
TI  - Efficacy of infliximab in Crohn's disease. Results of a retrospective multicenter
      study with a 15-month follow-up.
AB  - OBJECTIVES: To evaluate prescription practices and response to infliximab
      treatment for Crohn's disease (CD). PATIENTS AND METHODS: The files of CD
      patients treated with at least one infusion of infliximab treated in
      gastroenterology units belonging to university teaching hospitals of the Parisian
      hospitals group (Assistance Publique-Hopitaux de Paris (AP-HP) during the year
      2000 were analyzed retrospectively. RESULTS: One hundred and thirty-seven
      patients (36.0 +/- 12.7 years, 92 females) from 12 centers were studied.
      Indication for treatment was fistulae or perianal disease in 39% of patients,
      active Crohn's disease in 45% and mixed conditions in 16%. Mean follow-up was
      15.2 +/- 7.2 months. The overall response rate was 85%. No predictive factor of
      sustained remission could be identified. The mean time to relapse was to 3.9 +/-
      3.1 months. Thirty-eight patients were on maintenance therapy at the end of the
      follow up; 37% exhibiting progressive lost of response to treatment.
      Immunosuppressive therapy was added to infliximab in 78% of cases but response to
      infliximab was not modified by addition of immunosuppressive drugs. Adverse
      events, most frequently minor, were noted in 23% of the patients. CONCLUSION:
      This retrospective study confirms the efficacy and safety of infliximab in CD.

PMID- 16565660
TI  - [Nutritional therapy in inflammatory bowel disease].
AB  - Protein-energy malnutrition and specific nutrient deficiencies are common in
      inflammatory bowel diseases (IBD), more particularly in Crohn's disease. In
      adults, the use of artificial nutrition is indicated in the event of
      malnutrition, short bowel syndrome, or IBD refractory to all other treatments. In
      children, enteral nutrition has a place as first-line treatment to avoid side
      effects of corticosteroids on growth. The use, as a therapeutic tool, of specific
      nutrients (n-3 fatty acids, glutamine, antioxydant vitamins and minerals, TGF
      beta, probiotics...) seems interesting at the pathophysiological level.
      Nevertheless, these nutrients are still under evaluation and there are not enough
      available studies to recommend them in clinical routine. A very promising
      solution is the use of probiotics for the treatment of refractory pouchitis.

PMID- 16565662
TI  - [Current trend: endocrine tumors of the stomach, small bowel, colon and rectum].

PMID- 16565663
TI  - [Clinical cases: a well-differentiated endocrine tumor].

PMID- 16565665
TI  - [Questions for professor Philippe Ruszniewski].

PMID- 16565667
TI  - [High serum alkaline phosphatase level revealing a liver adenoma].
AB  - A 25-year-old woman had a high serum level of alkaline phosphatase activity (2571
      UI/L). Serum levels of transaminases, gamma glutamyl transferase and bilirubin
      were normal. Abdominal ultrasonography revealed a tumor nodule in the right liver
      lobe. There was no evidence of biliary obstruction. The serum activity of
      alkaline phosphatase returned to normal after surgical removal of the liver
      tumor. Histologic examination showed that the tumor was a liver adenoma with no
      evidence of degeneration. The adenoma cells reacted strongly positive to alkaline
      phosphatase by histochemical staining. The production of hepatic and biliary type
      alkaline phosphatase by the tumor is the most likely mechanism for the high serum
      levels observed in this patient.

PMID- 16565668
TI  - Fatal hepatic decompensation in a bone marrow transplant recipient with HBV
      related cirrhosis following lamivudine withdrawal.
AB  - Lamivudine is a nucleoside analogue with a potent antiviral activity used as
      prophylaxis against hepatitis B virus reactivation in patients with chronic HBV
      infection receiving chemotherapy. No standard guidelines exist, however, for the
      duration of lamivudine treatment. We report a clinical case of a 56-year-old
      patient with HBeAg-negative cirrhosis who developed a multiple myeloma. He was
      treated with lamivudine for 1 year while receiving chemotherapy and a subsequent
      bone marrow transplant. Complete remission from multiple myeloma was achieved.
      Four months after lamivudine was withdrawn, he experienced HBV reactivation with
      jaundice, though no YMDD mutations were detected. The patient rapidly developed
      fatal decompensation with septicemia and renal failure. In conclusion, this case
      shows that physicians should avoid discontinuing nucleoside therapy in patients
      with HBV infection who undergo immunosuppression for concomitant neoplastic
      conditions.

PMID- 16565669
TI  - [Multiple focal nodular hyperplasia of the liver associated with congenital
      absence of the portal vein].
AB  - We report the 32nd case of congenital absence of portal vein in an 18-year-old
      female adult associated with multiple focal nodular hyperplasia of the liver. The
      association of various hepatic tumors has been observed in half of the
      publications about congenital absence of portal vein. Hepatic tumors seem to
      result from systemic diversion of portal vein flow with a resultant increase of
      arterial flow causing important vascular and nutritif changes the liver and
      consequent parenchymal transformation.

PMID- 16565670
TI  - Extensive portal vein thrombosis related to abdominal trauma.
AB  - Abdominal trauma is a classic but very rare cause of portal vein thrombosis. We
      report the case of a patient with portal vein thrombosis and cavernoma associated
      with portal hypertension. Anamnesis identified a serious thoraco-abdominal trauma
      related to a bicycle accident 6 months before. Biological screening identified an
      inherited heterozygous G20210A factor II gene mutation which supports a recent
      notion that portal vein thrombosis most often occurs when both local and systemic
      aetiological factors are combined.

PMID- 16565671
TI  - [Solitary fibrous tumor of the pancreas. A case report].
AB  - Solitary fibrous tumour (SFT), a rare mesenchymal neoplasm usually arising from
      the pleura, may also occur in many other extra pleural sites. It has
      exceptionally been described in the pancreas. This report describes the case of a
      benign SFT of the pancreas occurring in a 41-year-old man who presented with a
      solid epigastric mass. Pathological and immunohistochemical findings are
      presented. Imaging features on ultrasonography, CT, MRI, and arteriography are
      widely detailed. Surgical resection of the tumour was performed, and the patient
      died from postoperative complications.

PMID- 16565672
TI  - [Multiple gastro-intestinal stromal tumors (GIST) in a patient with type I
      neurofibromatosis revealed by chronic bleeding: pre-operative radiological
      diagnosis].
AB  - Recent studies have pointed out a high incidence of GIST, usually multiple and of
      small intestinal location, in patients with type I neurofibromatosis. We here
      report an additional case, revealed by chronic gastro-intestinal bleeding and
      diagnosed at pre-operative imaging studies. A 56-year-old patient, with known
      type I neurofibromatosis, was referred to our department for the exploration of
      chronic gastro-intestinal bleeding during anti-aggregant therapy. Endoscopical
      examination was negative. Enteroscanner showed the presence of four tumor
      lesions, 3 in the jejunum and 1 in the ileum. Segmental surgical resections were
      performed. At histological examination, 2 of among the 3 jejunal lesions were
      diagnosed as typical GIST, of low risk of malignancy, CD117+, CD34+, whereas the
      last jejunal and ileal lesions were identified as fibroid tumors. Mutations of c
      kit gene and of the gene coding for PDGF-Ralpha were not detected. Post-operative
      recovery was uneventful; no recurrent bleeding was observed. Our case report
      underlines the potential role of enteroscanner in the management of patients with
      type I neurofibromatosis with possible digestive complications. It also
      emphasizes the importance of an accurate diagnosis of the digestive tumors
      associated with type I neurofibromatosis: GISTs are frequent in this setting and
      must not be misdiagnosed as neurofibromas.

PMID- 16565673
TI  - [Coma following chemotherapy: is 5FU implicated? Discussion about on case
      report].
AB  - 5FU is one of the most frequently used antioncogenic and cytostatic drug in
      digestive oncology. It may cause severe adverse events, such as encephalopathy,
      possibly based on hyperammoniemia, and may lead to coma. We report here the case
      of a coma with a favorable outcome following 5FU chemotherapy. As any other
      etiologic findings came to light, hyperammoniemia was discussed as a credible
      cause.

PMID- 16565674
TI  - [Resolution of Budd-Chiari syndrome with anticoagulant treatment].

PMID- 16565675
TI  - Feasibility of colonoscopy without sedation. A retrospective study of 502
      procedures.

PMID- 16565676
TI  - [Metastatic appendiceal adenocarcinoid].

PMID- 16565677
TI  - [Is the frequency of hemolytic uremic syndrome as a complication of gemcitabine
      underestimated? The role of systematic screening].

PMID- 16565679
TI  - Measuring change in rehabilitation medicine.

PMID- 16565678
TI  - Drug induced esophageal ulceration.

PMID- 16565681
TI  - Early rehabilitative treatment in patients with traumatic brain injuries: outcome
      at one-year follow-up.
AB  - AIM: The aim of this study was to analyze the outcome at one-year follow-up of
      patients with traumatic brain injuries (TBI) after 4 years of application of our
      organizing model and compare our results with the international data in terms of
      disability (functional independence measure [FIM], disability rating scale [DRS]
      scores) and social integration (community integration questionnaire [CIQ], work
      reentry) METHODS: We started a routine based on the presence of the physiatrist
      in the Intensive Care Unit (ICU) and Neurosurgery 3 times per week to evaluate
      all patients with TBI, program and control physiotherapeutic treatments and
      transfers to rehabilitative centers. Data were collected considering 80 TBI
      patients sequentially discharged from our department, from August 1999 to
      December 2003. The sample was composed of patients with severe brain injury
      evaluated at rehabilitation admission, rehabilitation discharge and one-year
      follow-up. We compared our data with those of the Traumatic Brain Injury Model
      System Data Base (TBI MSDB) and Gruppo Italiano per lo Studio delle
      Cerebrolesioni Acquisite Riabilitazione (GISCAR). RESULTS: Disability at one-year
      follow-up was better than at discharge: increase in FIM value, in DRS value.
      Social reintegration and return to work were not optimal: CIQ value was 16 and
      only 38% of patients returned to work at follow-up. Disability and social
      integration mean scores in our sample were similar to those obtained in TBI MSDB
      and so were the values of onset-admission interval (OAI) and length of stay
      (LOS). Differences were found with the Italian GISCAR database where mean OAI and
      LOS were higher than in our sample (55 and 86 days vs 18 and 37 days).
      CONCLUSIONS: Our data show that this kind of organizing model for the
      rehabilitative evolution of TBI patients can positively influence the cost
      efficiency rate of rehabilitation process reducing care costs in terms of ICU and
      rehabilitation LOS without affecting outcome in terms of disability and
      reintegration.

PMID- 16565680
TI  - Pharmacological interventions for spasticity following spinal cord injury:
      results of a Cochrane systematic review.
AB  - The aim of this paper was to assess the effectiveness and safety of baclofen,
      dantrolene, tizanidine and any other drugs for the treatment of long-term
      spasticity in spinal cord injury (SCI) patients, as well as the effectiveness and
      safety of different routes of administration of baclofen. A systematic review of
      randomised controlled trials (RCTs), within the Cochrane Collaboration Injuries
      Group, was carried out. The Cochrane Injuries Group Specialised Register, the
      Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINAHL were searched up
      to July 2006 without language restriction. Drug companies and experts active in
      the area were also contacted to find other relevant studies. Two investigators
      independently identified relevant studies, extracted data and assessed
      methodological quality of studies resolving disagreement by consensus. Nine out
      of 55 studies met the inclusion criteria. The heterogeneity among studies did not
      allow quantitative combination of RESULTS: Study designs were: 8 crossover, 1
      parallel-group trial. Two studies (14 SCI patients) showed a significant effect
      of intrathecal baclofen in reducing spasticity (Ashworth score and activities of
      daily living [ADL] performances), compared to placebo, without any adverse
      effect. The study comparing tizanidine to placebo (118 SCI patients) showed a
      significant effect of tizanidine in improving Ashworth score but not in ADL
      performances. The tizanidine group reported significant rates of adverse effects
      (drowsiness, xerostomia). For the other drugs (gabapentine, clonidine, diazepam,
      amytal and oral baclofen) the results do not provide evidence for a clinical
      significant effectiveness. This systematic review indicates that there is
      insufficient evidence to assist clinicians in a rational approach to antispastic
      treatment for SCI. Further research is urgently needed to improve the scientific
      basis of patient care.

PMID- 16565682
TI  - Percutaneous endoscopic gastrostomy: complications in the short and long-term
      follow-up and efficacy on nutritional status.
AB  - AIM: Percutaneous endoscopic gastrostomy (PEG) is an accepted procedure for
      patients at risk of malnutrition, but it requires an invasive procedure and many
      complications can occur. The aim of this study is to evaluate the long-term
      efficacy, morbidity and mortality of PEG. METHODS: We analysed 68 inpatients who
      underwent a PEG procedure between January 1999 and August 2006 in our
      rehabilitation unit. RESULTS: A total of 26.5% of the examined patients died, but
      none of them due to PEG-related complications. Out of the 18 patients who died, 8
      suffered from diabetes mellitus, thus showing a positive correlation between
      diabetes and mortality. The thirty-day mortality rate was of 1.5%; 30.9% of males
      and 23.1% of females developed an early peristomal infection, 4.4% of the
      patients suffered from stomal leakage, 1 patient pulled out the gastrostomy tube
      and 1 patient, accidentally, occurred to remove the tube. None major complication
      occurred. During the observation period nutritional parameters had been good in
      10 patients, who had been followed for 33.3 +/- 16.1 months. These indexes were
      reduced with a significant statistical difference in deaed patients. Only 20.6%
      of the patients improved their autonomy, valued by Barthel index (BI), while in
      the other patients BI remained = 10. CONCLUSIONS: This study confirmed the safety
      of PEG in terms of mortality and complications. The presence of diabetes mellitus
      increased mortality. The nutritional indexes were significantly reduced in deaed
      patients, while they remained good in the survivors. Nevertheless, a good
      nutrition had the slightest influence on the functional status.

PMID- 16565683
TI  - Physical rehabilitation and burnout: different aspects of the syndrome and
      comparison between healthcare professionals involved.
AB  - AIM: The aim of this study is to investigate burnout syndrome among physical
      rehabilitation professionals focusing on the differences between 4 categories of
      healthcare professionals involved. METHODS: The experimental group consisted of
      124 physiotherapy workers chosen among physicians, nurses, therapists, and
      technicians. The variables we chose to measure were: the presence of burnout
      (emotional exhaustion, depersonalization and lack of personal accomplishment),
      feelings of depression and anger, symptoms of psychological uneasiness and the
      level of perceived stress. RESULTS: Overall the level of burnout experienced was
      medium-low. Emotional exhaustion was more prevalent among physiotherapists, while
      depersonalization was higher among physicians. Moreover mild feelings of
      depression emerged among technicians. No differences were found among the 4
      categories when feelings of anger were considered, although anger was present at
      different levels (and more or less expressed) throughout the working environment.
      CONCLUSIONS: Some considerations on the nature and possible causes of
      psychological distress emerged from the work carried out with the groups of
      healthcare professionals and some possible areas of intervention are suggested.

PMID- 16565684
TI  - The compangle: a new goniometer for joint angle measurements of the hand. A
      technical note.
AB  - The accuracy of joint angle measurement of the hand may be negatively influenced
      by joint swelling, deformation and other obstacles. We developed an alternative
      goniometer with clear ergonomic advantages, especially for the measurement of
      small joints. This new concept of goniometry is described and preliminary results
      on the reliability of the measurements are presented. The intraclass correlation
      coefficients (ICCs) and the standard error of measurements (SEMs) of the
      alternative goniometer are greater respectively smaller than a conventional
      goniometer, indicating a better intratester reliability.

PMID- 16565685
TI  - The treatment of facial palsy from the point of view of physical and
      rehabilitation medicine.
AB  - There are evidences to support recommending the early intake of prednisone (in
      its appropriate dose of 1 mg/kg body weight for up to 70 or 80 mg/day) or the
      combined use of prednisone and acyclovir (or valacyclovir) within 72 h following
      the onset of paralysis in order to improve the outcome of Bell's palsy (BP).
      Although there may be a controversy about the role of physiotherapy in BP or
      facial palsy, it seemed that local superficial heat therapy, massage, exercises,
      electrical stimulation and biofeedback training have a place in the treatment of
      lower motor facial palsy. However, each modality has its indications. Moreover,
      some rehabilitative surgical methods might be of benefit for some patients with
      traumatic facial injuries or long standing paralysis without recovery, but early
      surgery in BP is usually not recommended. However, few may recommend early
      surgery in BP when there is 90-100% facial nerve degeneration. The efficacy of
      acupuncture, magnetic pellets and other modalities of physiotherapy needs further
      investigation. The general principles and the different opinions in treating and
      rehabilitating facial palsy are discussed and the need for further research in
      this field is suggested.

PMID- 16565686
TI  - Cognitive rehabilitation of attention deficit after brain damage: from research
      to clinical practice.

PMID- 16565687
TI  - Individual differences and attentional varieties.
AB  - With its own functional anatomy, circuitry and cellular structure, attention can
      be viewed as an organ system. This conceptualization reframes many problems in
      cognitive science and permits important insights into neurological and
      psychiatric disorders of both children and adults. Specifically, construing
      attention as an organ system helps to describe the evolutionary and developmental
      aspects of volitional control, thus paving the road towards a better appreciation
      of how such factors as genetics and culture influence control systems. The
      efficiency of the attention networks differs between people. However, these
      individual differences may elucidate variation in intelligence as well as the
      ability to regulate affect.

PMID- 16565688
TI  - Attention rehabilitation following stroke and traumatic brain injury. A review.
AB  - Attentional capacities, which are frequently impaired following brain injury,
      have also been found to be amenable to rehabilitation. This review discusses
      various approaches to attention rehabilitation in adult clients following stroke
      and traumatic brain injury. Attention process training has been accepted by many
      as a practice standard in postacute clients, however, its ability to generalize
      to new situations and to functional capacities is unclear. There is evidence for
      the use of psychostimulant medication, which may be most helpful when prescribed
      in combination with attention training. Biofeedback is a new avenue for
      intervention and is beginning to show some promising RESULTS: Rather than train
      underlying processes, another approach which shows promising results in a few
      small studies is training clients on specific functional skills, such as driving
      or vocational duties. Finally, modifications to the environment, implementation
      of strategies, provision of emotional support, and introduction of external
      supports/aids are important parts of a rehabilitation program, especially as the
      client returns to their home environment.

PMID- 16565689
TI  - National Consensus Conference. The rehabilitation management of traumatic brain
      injury patients during the acute phase: criteria for referral and transfer from
      intensive care units to rehabilitative facilities (Modena June 20-21, 2000).

PMID- 16565690
TI  - [Metabolic syndrome: current issues and perspectives].

PMID- 16565691
TI  - [The future of the metabolic syndrome: certainties, open questions and
      discussions].
AB  - The metabolic syndrome is a topic of hot debate among experts due to different
      opinions about its definition and its clinical relevance. The metabolic syndrome
      is identified by the presence of abnormalities of the glucose metabolism, blood
      pressure, fat deposition, and some plasma lipids. Several authors have attempted
      to find a physiopathological explanation for the association of the abnormalities
      in this syndrome. Recently, some aspects of the inflammation seem relevant to
      understand the association of visceral fat deposition, insulin-resistance and
      diabetes and vascular complications. From a clinical point of view this syndrome
      must be considered an important vascular risk factor.

PMID- 16565692
TI  - The bacterium behind the 2005 Nobel Prize.

PMID- 16565693
TI  - Transmission of Helicobacter pylori: are there evidences for a fecal-oral route?
AB  - Helicobacter pylori (H. pylori) infection spreads from person-to-person, however
      the precise mode of transmission (oral-oral, fecal-oral or gastro-gastric) is
      hitherto not known. Gaining understanding into the spread of the bacterium might
      be useful in identifying high-risk populations, especially in areas that have
      high rates of gastric malignancies or peptic ulcer. In this review, the authors
      analyze the aspects concerning the plausibility for the fecal-oral route on the
      basis of the available data.

PMID- 16565694
TI  - [Non-invasive diagnosis of Helicobacter pylori infection in the 2006 clinical
      practice].
AB  - At present, 2 approaches are used to detect Helicobacter pylori (H. pylori):
      invasive, if based on biopsies taken during endoscopy, and non-invasive, if they
      do not rely on endoscopic approach. A 3rd option is offered by the string test,
      that employs an invasive non-endoscopic strategy. The present review attempts to
      update on the diagnostic non-invasive approaches to patients in the clinical
      setting. Non-invasive tests include urea breath test (UBT), antigen stool assay,
      serology, and ''doctor's tests''. The choice of the methods depends on the
      situation, for example, the clinical circumstances, the diagnostic accuracy, the
      costs of the testing strategy, and the availability of the tests in the
      respective area. According to European guidelines, UBT and antigen stool assay
      are recommended in patients without alarm symptoms or under 45 years of age, at
      low risk of malignancy in the test and treat strategy. Confirmation of H. pylori
      eradication following treatment should be tested by UBT; the stool antigen assay
      is the alternative if the former is not available.

PMID- 16565695
TI  - [Invasive diagnosis of Helicobacter pylori infection in the 2006 clinical
      practice].
AB  - Currently, different approaches are employed to detect the presence of
      Helicobacter pylori (H. pylori): invasive, if based on biopsies performed during
      endoscopy (urease test, histology, culture, polymerase chain reaction), and non
      invasive, if endoscopy is not carried out. Another option is offered by the
      invasive non-endoscopic methods (string test). An update on the diagnostic
      invasive approaches to patients in the clinical setting is presented in this
      review. Although non-invasive tests are preferred, important information can be
      gained from histology, the unique technique which permits the evaluation of the
      status of the mucosa, and from culture, that allows strain typing and tests for
      antibiotic susceptibility. Until today, polymerase chain reaction has had a
      limited application in the clinical practice and the role of non-endoscopic
      methods needs to be better clarified in the future.

PMID- 16565696
TI  - [Gastric cancer and Helicobacter pylori: an interdisciplinary point of view].
AB  - Gastric carcinogenesis involves a slow but continuous, stepwise evolution from
      superficial gastritis to glandular atrophy, metaplasia, dysplasia, and finally,
      to adenocarcinoma. In 1994, the International Agency for Research on Cancer
      defined Helicobacter pylori (H. pylori) as a group I carcinogen. Evidence
      supporting a causal association has been demonstrated by epidemiological data as
      well as by experimental animal models. The process of carcinogenesis, which may
      well extend over decades, provides an excellent opportunity for prevention or
      early detection of the events preceding development of the neoplasm. This is
      especially true because, at present, H. pylori can be readily treated. Despite
      this, the prognosis for gastric cancer is poor and, in most industrialised
      countries, the survival is only 10% after 5 years from diagnosis. The sole
      exception is Japan where this malignancy is often identified at an early stage
      when cure by radical surgery is more probable.

PMID- 16565697
TI  - Extragastric manifestations of Helicobacter pylori infection.
AB  - Since the discovery of Helicobacter pylory (H. pylori), several studies have been
      published concerning a hypothetical role of this bacterium in different
      extragastric diseases, such as ischemic heart disease, idiopathic
      thrombocytopenic purpura, iron deficiency anemia or other disorders. The majority
      of those studies may be classified as epidemiological or eradicating trials but
      there are also case reports or in vitro studies. Idiopathic thromobocytopenic
      purpura represents the disease showing a stronger link with H. pylori infection.
      There are also increasing evidences on the role of H. pylori infection in iron
      deficiency anemia and ischemic heart disease. On the contrary, the association
      between H. pylori infection and other diseases is still controversial, as is
      supported in the majority of the cases by case reports, small pilot studies or
      just in vitro data.

PMID- 16565698
TI  - Role of Helicobacter pylori infection in peptic ulcer haemorrhage.
AB  - AIM: In spite of the diffusion of endoscopic treatment, mortality rate due to
      peptic ulcer haemorrhage (PUH) remains high. Helicobacter pylori (H. pylori)
      infection and nonsteroidal anti-inflammatory drugs (NSAIDs) are the 2 main
      aetiological factors, but their interactive role is controversial. The aim of
      this study was to determine both the prevalence of H. pylori infection and NSAIDs
      consumption in PUH and their prognostic importance. METHODS: In a prospective
      study, 41 consecutive patients (33 males, 8 females) admitted for PUH were
      recruited. H. pylori status was investigated both by measuring specific
      antibodies in serum and by histological detection on gastric biopsies obtained
      after one month from bleeding. In case of doubt, either a 13C urea breath test,
      or a stool antigen test were associated. All patients were treated with medical
      therapy associated to endoscopic treatment in most severe cases. RESULTS: Sixteen
      patients were infected from H. pylori (group A), 12 had a history of NSAIDs
      consumption (group B), and 13 had both risk factors (group C). The median
      duration of hospitalisation was 7 days for each group and correlated with age
      (P<0.04). Severity of PUH (high risk of rebleeding) was higher in group A (13/16;
      81%) and group C (9/13; 69%), with respect to group B (6/12; 50%). This
      difference was not significant. CONCLUSIONS: H. pylori infection has a
      predominant role in causing PUH as well as in the prognosis and clinical course
      of this condition. Hence, it is important to determine H. pylori status in every
      patient with PUH.

PMID- 16565699
TI  - [Benefit from bio-enteric Intra-gastric balloon (BIB) to modify lifestyle and
      eating habits in severely obese patients eligible for bariatric surgery].
AB  - AIM: The therapeutic model for severe obesity includes bariatric surgery,
      representing the safest way to keep weight down and to prevent relapses. The
      selection of patients for the most suitable type of surgery implies
      multidisciplinary approach (nutritionist, dietist, clinical psychologist and
      surgeon). The intragastric balloon may represent a relatively invasive method to
      help the medical team to select and prepare severely obese patients for
      restrictive bariatric surgery. METHODS: In our study we considered 48 severely
      obese patients: initial weight 111+/-14.8 kg, BMI 43+/-5.02, excess weight
      77.47+/-16.14%. These patients have been treated with intragastric balloon (BIB)
      filled to a volume of 500 cc for 6 months. We considered variations induced by
      BIB treatment on a number of parameters--clinical, anthropometric, food intake,
      partition of nourishing elements and psychological and psychometric data.
      RESULTS: At the end of the treatment the patients showed significant reductions
      of excess weight (67.35+/-20.19%), of weight (103.4+/-16.72 kg) and food intake,
      without modification of the items in the EDI2 test, but with important
      motivational support for a change in life style between the beginning and the end
      of the treatment, clearly resulting from the medical, dietist and clinical
      psychological follow-up. CONCLUSIONS: BIB is a relatively invasive means capable
      of modifying eating habits in the short term; it induces weight loss, may help to
      reduce the anaesthesiological risk and to foster a change in the patient's
      behaviour. In our experience treatment with BIB is useful from the educational
      point of view and can be used to select patients for bariatric surgery only
      within a multidisciplinary team. Further clinical studies are necessary.

PMID- 16565700
TI  - Sperm output in patients with primary infertility and hepatitis B or C virus;
      negative influence of HBV infection during concomitant varicocele.
AB  - AIM: The aim of this study was to evaluate the sperm abnormalities in young
      infertile patients with hepatitis B (HBV) or C (HCV) virus infection and to
      evaluate the additional negative influence of varicocele on sperm parameters in
      these patients. METHODS: Part I. Forty-two infertile patients in Child-Pugh
      classification A with HBV (n=23) or HCV (n=19) infection, underwent sperm
      analysis and quantitative detection of HBV-DNA or HCV-RNA in blood serum. Sperm
      parameters were compared to those of a group of 30 patients with primary
      infertility due to causes different from liver diseases and/or varicocele). Part
      II. Twenty-one infertile patients with varicocele associated to HBV (n=11) or HCV
      (n=10) infection were also enrolled and underwent semen analysis: a group of 39
      patients without liver disease, but with varicocele alone served as matched
      control group. RESULTS: Part I. HBV patients (with a median HBV-DNA load of
      6x10(5) copies/mL, range 1x10(5)-10x10(6)) showed median sperm parameters (sperm
      density, total number, forward motility and morphology, viability) significantly
      worse than those found in patients with HCV (with a median HCV-RNA load of
      2.3x10(6) copies/mL, range (2x10(5)-12x10(6)). Sperm parameters showed no
      significant correlation with the duration of infertility neither with the
      duration of viral infection. Sperm morphology only, exhibited a trend (P=0.06) of
      negative correlationship (r=-0.59) with the viral HBV-DNA load, whereas the other
      sperm parameters studied showed no correlation with the viral load. Part II. The
      group of infertile patients with HBV and varicocele showed median values of all
      sperm parameter evaluated significantly worse than those found in infertile
      patients with varicocele alone, or with HCV infection plus varicocele.
      CONCLUSIONS: Patients with HBV infection show worse sperm parameters compared
      with HCV patients. The additional presence of varicocele further impairs sperm
      output in HBV patients.

PMID- 16565701
TI  - [The cardiac natriuretic peptides].
AB  - Cardiac natriuretic peptides (including ANP, BNP, CNP and urodilatin) constitute
      a family of peptide hormones and neurotransmitters, sharing similar chemical
      structure (characterized by a cysteine bridge) and biological function. ANP and
      BNP are cardiac hormones because they are principally produced and secreted by
      cardiomyocytes. CNP is principally produced and secreted by endothelial cells,
      while urodilatin only by renal tubular cells. Natriuretic peptides share a direct
      diuretic, natriuretic and vasodilator effect and an inhibitory action on
      ventricular myocyte contraction as well as on remodeling, restenosis and other
      inflammatory processes of myocardium and smooth muscle cells. Cardiac natriuretic
      peptides share their biological action by means of specific receptors (NPR),
      which are present into the cell membranes of target tissues. Three different
      subtypes of NPRs have been so far identified in mammalian tissues. NPR-A and NPR
      B are generally considered to mediate all known biological actions throughout the
      guanylate cyclase (GC) intracellular domain, while the third member of the
      natriuretic peptide receptor family, the NPR-C receptor, has not a GC domain. It
      is generally thought that the NPR-C is not linked to GC and so serves as a
      clearance receptor. Natriuretic peptides constitute a family sharing both
      endocrine. paracrine and autocrine actions and neurotransmitter and immuno
      modulator functions. Therefore, it can be hypothesized that the cardiac
      natriuretic peptide system is closely related with other regulatory systems in a
      biological hierarchical networks.

PMID- 16565702
TI  - [Management of uncomplicated arterial hypertension in pregnancy].
AB  - In the management of uncomplicated arterial hypertension in pregnancy, blood
      pressure (BP) values of pregnant women should be treated in order to reduce risks
      of both maternal and fetal complications. To reduce these risks, it is necessary
      to monitor BP, some hematochemical parameters and albuminuria, to try to prevent
      more serious clinical complications. Moreover, repeated measurements of BP, as
      well as frequent ambulatory blood pressure monitoring (ABPM) over 24 h are
      necessary. In the treatment of hypertension in pregnancy, if there are no high
      risks, it is possible to try a non pharmacological antihypertensive therapy
      consisting of a suitable diet, reduction of weight, abolition of some lifestyles
      (smoking, excessive alcohol consumption and heavy physical exercises). If these
      measures are not sufficient or the risk is high, a pharmacological therapy with
      neither toxic nor teratogenic drugs for the fetus will be administered in order
      to normalize BP without reducing perfusion of the uterus/placenta. Only in case
      of severe hypertension, a more aggressive pharmacological treatment should be
      carried out and, if necessary, hospitalization. The drugs suggested in these
      cases are those which have already been recognised as presenting low side
      effects. Antihypertensive drugs used in pregnancy can be classified as: suitable
      (methyldopa, clonidine, long acting calcioantagonists); cautiously used (alpha
      blockers, beta-betablockers); contraindicated (ACE-inhibitors, sartans, short
      acting calcioantagonists). Hyper-tensive crises should be treated with an
      injection therapy (clonidine, labetalol), with hospital admission if necessary,
      or if preeclampsia or eclampsia may occur.

PMID- 16565703
TI  - [Treatment of colorectal cancer liver metastases].
AB  - Liver is the main target for colorectal cancer (CRC) metastases. About 50% of all
      patients affected by CRC develop liver metastases. Surgery remains the only
      potentially curative strategy and indications to surgery and resectability
      criteria are now less restrictive than before so that a more aggressive attitude
      in the treatment of metastatic lesions is the rule. However surgery is not
      possible in the majority of patients. For non resectable patients two options are
      available: local treatment strategies (Radio-frequency ablation and Cryosurgery:
      alone or in combination with surgery) and chemotherapy. High rates of objective
      response achieved with Fluoropyrimidines, Oxaliplatin (OHP) and Irinotecan (CPT
      11) based chemo-therapy, enable initially unresectable patients to undergo
      surgery, with a 5-year survival rate comparable to that observed for primary
      resectable patients. Therefore chemotherapy has not only a palliative aim, but
      becomes a fundamental moment of a combined medical and surgical treatment with
      curative purpose. After surgery two-thirds of patients will relapse in first two
      years, so that adjuvant therapy has been investigated to reduce recurrence rates,
      mainly testing hepatic arterial infusion (HAI) schedules. So far no randomized
      trials have been published on the role of systemic intravenous adjuvant chemo
      therapy. Finally we report the results of our monoinstitutional experience,
      suggesting a possible role of systemic adjuvant chemotherapy in reducing
      recurrence rates after liver metastasectomy. Probably in the next years new
      targeted drugs and locoregional therapies will contribute to further improve
      prognosis of such patients, in a neoadjuvant, adjuvant and palliative setting.

PMID- 16565704
TI  - Pluripotency of spermatogonial stem cells from adult mouse testis.
AB  - Embryonic germ cells as well as germline stem cells from neonatal mouse testis
      are pluripotent and have differentiation potential similar to embryonic stem
      cells, suggesting that the germline lineage may retain the ability to generate
      pluripotent cells. However, until now there has been no evidence for the
      pluripotency and plasticity of adult spermatogonial stem cells (SSCs), which are
      responsible for maintaining spermatogenesis throughout life in the male. Here we
      show the isolation of SSCs from adult mouse testis using genetic selection, with
      a success rate of 27%. These isolated SSCs respond to culture conditions and
      acquire embryonic stem cell properties. We name these cells multipotent adult
      germline stem cells (maGSCs). They are able to spontaneously differentiate into
      derivatives of the three embryonic germ layers in vitro and generate teratomas in
      immunodeficient mice. When injected into an early blastocyst, SSCs contribute to
      the development of various organs and show germline transmission. Thus, the
      capacity to form multipotent cells persists in adult mouse testis. Establishment
      of human maGSCs from testicular biopsies may allow individual cell-based therapy
      without the ethical and immunological problems associated with human embryonic
      stem cells. Furthermore, these cells may provide new opportunities to study
      genetic diseases in various cell lineages.

PMID- 16565705
TI  - RNAi-mediated gene silencing in non-human primates.
AB  - The opportunity to harness the RNA interference (RNAi) pathway to silence disease
      causing genes holds great promise for the development of therapeutics directed
      against targets that are otherwise not addressable with current medicines.
      Although there are numerous examples of in vivo silencing of target genes after
      local delivery of small interfering RNAs (siRNAs), there remain only a few
      reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and
      there are no reports of systemic efficacy in non-rodent species. Here we show
      that siRNAs, when delivered systemically in a liposomal formulation, can silence
      the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific
      siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and
      administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5
      mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB
      messenger RNA expression in the liver 48 h after administration, with maximal
      silencing of >90%. This silencing effect occurred as a result of APOB mRNA
      cleavage at precisely the site predicted for the RNAi mechanism. Significant
      reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels
      were observed as early as 24 h after treatment and lasted for 11 days at the
      highest siRNA dose, thus demonstrating an immediate, potent and lasting
      biological effect of siRNA treatment. Our findings show clinically relevant RNAi
      mediated gene silencing in non-human primates, supporting RNAi therapeutics as a
      potential new class of drugs.

PMID- 16565708
TI  - DNA methyltransferases control telomere length and telomere recombination in
      mammalian cells.
AB  - Here, we describe a role for mammalian DNA methyltransferases (DNMTs) in telomere
      length control. Mouse embryonic stem (ES) cells genetically deficient for DNMT1,
      or both DNMT3a and DNMT3b have dramatically elongated telomeres compared with
      wild-type controls. Mammalian telomere repeats (TTAGGG) lack the canonical CpG
      methylation site. However, we demonstrate that mouse subtelomeric regions are
      heavily methylated, and that this modification is decreased in DNMT-deficient
      cells. We show that other heterochromatic marks, such as histone 3 Lys 9 (H3K9)
      and histone 4 Lys 20 (H4K20) trimethylation, remain at both subtelomeric and
      telomeric regions in these cells. Lack of DNMTs also resulted in increased
      telomeric recombination as indicated by sister-chromatid exchanges involving
      telomeric sequences, and by the presence of 'alternative lengthening of
      telomeres' (ALT)-associated promyelocytic leukaemia (PML) bodies (APBs). This
      increased telomeric recombination may lead to telomere-length changes, although
      our results do not exclude a potential involvement of telomerase and telomere
      binding proteins in the aberrant telomere elongation observed in DNMT-deficient
      cells. Together, these results demonstrate a previously unappreciated role for
      DNA methylation in maintaining telomere integrity.

PMID- 16565707
TI  - In vitro germline potential of stem cells derived from fetal porcine skin.
AB  - Two of the unanswered questions in mammalian developmental biology are when and
      where the fate of the germ cell is specified. Here, we report that stem cells
      isolated from the skin of porcine fetuses have the intrinsic ability to
      differentiate into oocyte-like cells. When differentiation was induced, a
      subpopulation of these cells expressed markers such as Oct4, Growth
      differentiation factor 9b (GDF9b), the Deleted in Azoospermia-like (DAZL) gene
      and Vasa - all consistent with germ-cell formation. On further differentiation,
      these cells formed follicle-like aggregates that secreted oestradiol and
      progesterone and responded to gonadotropin stimulation. Some of these aggregates
      extruded large oocyte-like cells that expressed oocyte markers, such as zona
      pellucida, and the meiosis marker, synaptonemal complex protein 3 (SCP3). Some of
      these oocyte-like cells spontaneously developed into parthenogenetic embryo-like
      structures. The ability to generate oocyte-like cells from skin-derived cells may
      offer new possibilities for tissue therapy and provide a new in vitro model to
      study germ-cell formation and oogenesis.

PMID- 16565709
TI  - Regulation of caveolar endocytosis by syntaxin 6-dependent delivery of membrane
      components to the cell surface.
AB  - Caveolar endocytosis has an important function in the cellular uptake of some
      bacterial toxins, viruses and circulating proteins. However, the molecular
      machinery involved in regulating caveolar uptake is poorly defined. Here, we
      demonstrate that caveolar endocytosis is regulated by syntaxin 6, a target
      membrane soluble N-ethylmaleimide attachment protein receptor (t-SNARE) involved
      in membrane fusion events along the secretory pathway. When syntaxin 6 function
      was inhibited, internalization through caveolae was dramatically reduced, whereas
      other endocytic mechanisms were unaffected. Syntaxin 6 inhibition also reduced
      the presence of caveolin-1 and caveolae at the plasma membrane. In addition,
      syntaxin 6 inhibition decreased the delivery of GM1 ganglioside (GM1) and
      glycosylphosphatidylinositol (GPI)-GFP (but not vesicular stomatitis virus
      glycoprotein G; VSV-G) protein from the Golgi complex to the plasma membrane.
      Addition of GM1 to syntaxin 6-inhibited cells resulted in the reappearance of
      caveolin-1 and caveolae at the plasma membrane, and restored caveolar uptake.
      These results suggest that syntaxin 6 regulates the delivery of microdomain
      associated lipids and proteins to the cell surface, which are required for
      caveolar endocytosis.

PMID- 16565710
TI  - Topographic control of lipid-raft reconstitution in model membranes.
AB  - Liquid-ordered (L(O)) domains reconstituted in model membranes have provided a
      useful platform for in vitro studies of the lipid-raft model, in which signalling
      membrane molecules are thought to be compartmentalized in sphingolipid- and
      cholesterol-rich domains. These in vitro studies, however, have relied on an
      uncontrolled phase-separation process that gives a random distribution of L(O)
      domains. Obviously, a precise control of the size and spatial distribution of the
      L(O) domains would enable a more systematic large-scale in vitro study of the
      lipid-raft model. The prerequisite for such capability would be the generation of
      a well-defined energy landscape for reconstituting the L(O) domain without
      disrupting the two-dimensional (2D) fluidity of the model membrane. Here we
      report controlling the reconstitution of the L(O) domains in a spatially
      selective manner by predefining a landscape of energy barriers using topographic
      surface modifications. We show that the selective reconstitution spontaneously
      arises from the 2D brownian motion of nanoscale L(O) domains and signalling
      molecules captured in these nanodomains, which in turn produce a prescribed,
      concentrated downstream biochemical process. Our approach opens up the
      possibility of engineering model biological membranes by taking advantage of the
      intrinsic 2D fluidity. Moreover, our results indicate that the topographic
      configuration of cellular membranes could be an important machinery for
      controlling the lipid raft in vivo.

PMID- 16565711
TI  - Electronic structure origins of polarity-dependent high-TC ferromagnetism in
      oxide-diluted magnetic semiconductors.
AB  - Future spintronics technologies based on diluted magnetic semiconductors (DMSs)
      will rely heavily on a sound understanding of the microscopic origins of
      ferromagnetism in such materials. Discoveries of room-temperature ferromagnetism
      in wide-bandgap DMSs hold great promise, but this ferromagnetism remains poorly
      understood. Here we demonstrate a close link between the electronic structures
      and polarity-dependent high-TC ferromagnetism of TM(2+):ZnO DMSs, where TM(2+)
      denotes 3d transition metal ions. Trends in ferromagnetism across the 3d series
      of TM(2+):ZnO DMSs predicted from the energies of donor- and acceptor-type
      excited states reproduce experimental trends well. These results provide a
      unified basis for understanding both n- and p-type ferromagnetic oxide DMSs.

PMID- 16565712
TI  - Switching the electrical resistance of individual dislocations in single
      crystalline SrTiO3.
AB  - The great variability in the electrical properties of multinary oxide materials,
      ranging from insulating, through semiconducting to metallic behaviour, has given
      rise to the idea of modulating the electronic properties on a nanometre scale for
      high-density electronic memory devices. A particularly promising aspect seems to
      be the ability of perovskites to provide bistable switching of the conductance
      between non-metallic and metallic behaviour by the application of an appropriate
      electric field. Here we demonstrate that the switching behaviour is an intrinsic
      feature of naturally occurring dislocations in single crystals of a prototypical
      ternary oxide, SrTiO(3). The phenomenon is shown to originate from local
      modulations of the oxygen content and to be related to the self-doping capability
      of the early transition metal oxides. Our results show that extended defects,
      such as dislocations, can act as bistable nanowires and hold technological
      promise for terabit memory devices.

PMID- 16565713
TI  - Enhancement of spin coherence using Q-factor engineering in semiconductor
      microdisc lasers.
AB  - Semiconductor microcavities offer unique means of controlling light-matter
      interactions in confined geometries, resulting in a wide range of applications in
      optical communications and inspiring proposals for quantum information processing
      and computational schemes. Studies of spin dynamics in microcavities, a new and
      promising research field, have revealed effects such as polarization beats,
      stimulated spin scattering and giant Faraday rotation. Here, we study the
      electron spin dynamics in optically pumped GaAs microdisc lasers with quantum
      wells and interface-fluctuation quantum dots in the active region. In particular,
      we examine how the electron spin dynamics are modified by the stimulated emission
      in the discs, and observe an enhancement of the spin-coherence time when the
      optical excitation is in resonance with a high-quality (Q approximately 5,000)
      lasing mode. This resonant enhancement, contrary to expectations from the
      observed trend in the carrier-recombination time, is then manipulated by altering
      the cavity design and dimensions. In analogy with devices based on excitonic
      coherence, this ability to engineer coherent interactions between electron spins
      and photons may provide new pathways towards spin-dependent quantum
      optoelectronics.

PMID- 16565714
TI  - Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains
      accelerate alpha-synuclein fibrilization.
AB  - Oxidative stress, inflammation and alpha-synuclein overexpression confer risk for
      development of alpha-synucleinopathies-neurodegenerative diseases that include
      Parkinson disease and Lewy body dementia. Dopaminergic neurons undergo
      degeneration in these diseases and are particularly susceptible to oxidative
      stress because dopamine metabolism itself creates reactive oxygen species.
      Intraneuronal deposition of alpha-synuclein as amyloid fibrils or Lewy bodies is
      the hallmark of these diseases. Herein, we demonstrate that concentrations of
      oxidative cholesterol metabolites derived from reactive oxygen species are
      elevated in the cortices of individuals with Lewy body dementia relative to those
      of age-matched controls, and we show that these metabolites accelerate alpha
      synuclein aggregation in vitro. The increase in the production of these cytotoxic
      cholesterol metabolites is also observed in a dopaminergic cell line that
      overexpresses alpha-synuclein. By extension, these data lead to the hypothesis
      that oxidative stress produces cholesterol aldehydes that enable alpha-synuclein
      aggregation, leading to a pathologic cycle.

PMID- 16565715
TI  - Proteomic profiling of metalloprotease activities with cocktails of active-site
      probes.
AB  - Metalloproteases are a large, diverse class of enzymes involved in many
      physiological and disease processes. Metalloproteases are regulated by post
      translational mechanisms that diminish the effectiveness of conventional genomic
      and proteomic methods for their functional characterization. Chemical probes
      directed at active sites offer a potential way to measure metalloprotease
      activities in biological systems; however, large variations in structure limit
      the scope of any single small-molecule probe aimed at profiling this enzyme
      class. Here, we address this problem by creating a library of metalloprotease
      directed probes that show complementary target selectivity. These probes were
      applied as a 'cocktail' to proteomes and their labeling profiles were analyzed
      collectively using an advanced liquid chromatography-mass spectrometry platform.
      More than 20 metalloproteases were identified, including members from nearly all
      of the major branches of this enzyme class. These findings suggest that chemical
      proteomic methods can serve as a universal strategy to profile the activity of
      the metalloprotease superfamily in complex biological systems.

PMID- 16565716
TI  - Chemical modulation of receptor signaling inhibits regenerative angiogenesis in
      adult zebrafish.
AB  - We examined the role of angiogenesis and the need for receptor signaling using
      chemical inhibition of the vascular endothelial growth factor receptor in the
      adult zebrafish tail fin. Using a small-molecule inhibitor, we were able to exert
      precise control over blood vessel regeneration. An angiogenic limit to tissue
      regeneration was determined, as avascular tissue containing skin, pigment,
      neuronal axons and bone precursors could regenerate up to about 1 mm. This
      indicates that tissues can regenerate without direct interaction with endothelial
      cells and at a distance from blood supply. We also investigated whether the
      effects of chemical inhibition could be enhanced in zebrafish vascular mutants.
      We found that adult zebrafish, heterozygous for a mutation in the critical
      receptor effector phospholipase Cgamma1, show a greater sensitivity to chemical
      inhibition. This study illustrates the utility of the adult zebrafish as a new
      model system for receptor signaling and chemical biology.

PMID- 16565717
TI  - Inhibition of multidrug resistance transporter-1 facilitates neuroprotective
      therapies after focal cerebral ischemia.
AB  - The blood-brain barrier possesses active transporters carrying brain-permeable
      xenobiotics back into the blood against concentration gradients. We demonstrate
      that multidrug resistance transporter (Mdr)-1 is upregulated on capillary
      endothelium after focal cerebral ischemia; moreover, Mdr-1 deactivation by
      pharmacological inhibition or genetic knockout preferably enhances the
      accumulation and efficacy of two neuroprotectants known as Mdr-1 substrates in
      the ischemic brain. We predict that Mdr-1 inhibition may greatly facilitate
      neuroprotective therapies.

PMID- 16565718
TI  - Genetic clonal diversity predicts progression to esophageal adenocarcinoma.
AB  - Neoplasms are thought to progress to cancer through genetic instability
      generating cellular diversity and clonal expansions driven by selection for
      mutations in cancer genes. Despite advances in the study of molecular biology of
      cancer genes, relatively little is known about evolutionary mechanisms that drive
      neoplastic progression. It is unknown, for example, which may be more predictive
      of future progression of a neoplasm: genetic homogenization of the neoplasm,
      possibly caused by a clonal expansion, or the accumulation of clonal diversity.
      Here, in a prospective study, we show that clonal diversity measures adapted from
      ecology and evolution can predict progression to adenocarcinoma in the
      premalignant condition known as Barrett's esophagus, even when controlling for
      established genetic risk factors, including lesions in TP53 (p53; ref. 6) and
      ploidy abnormalities. Progression to cancer through accumulation of clonal
      diversity, on which natural selection acts, may be a fundamental principle of
      neoplasia with important clinical implications.

PMID- 16565719
TI  - Lethal influenza infection in the absence of the natural killer cell receptor
      gene Ncr1.
AB  - The elimination of viruses and tumors by natural killer cells is mediated by
      specific natural killer cell receptors. To study the in vivo function of a
      principal activating natural killer cell receptor, NCR1 (NKp46 in humans), we
      replaced the gene encoding this receptor (Ncr1) with a green fluorescent protein
      reporter cassette. There was enhanced spread of certain tumors in 129/Sv but not
      C57BL/6 Ncr1(gfp/gfp) mice, and influenza virus infection was lethal in both
      129/Sv and C57BL/6 Ncr1(gfp/gfp) mice. We noted accumulation of natural killer
      cells at the site of influenza infection by tracking the green fluorescent
      protein. Our results demonstrate a critical function for Ncr1 in the in vivo
      eradication of influenza virus.

PMID- 16565720
TI  - Transcriptional repressor Blimp-1 is essential for T cell homeostasis and self
      tolerance.
AB  - T cell homeostasis is crucial for a functional immune system, as the accumulation
      of T cells resulting from lack of regulatory T cells or an inability to shut down
      immune responses can lead to inflammation and autoimmune pathology. Here we show
      that Blimp-1, a transcriptional repressor that is a 'master regulator' of
      terminal B cell differentiation, was expressed in a subset of antigen-experienced
      CD4(+) and CD8(+) T cells. Mice reconstituted with fetal liver stem cells
      expressing a mutant Blimp-1 lacking the DNA-binding domain developed a lethal
      multiorgan inflammatory disease caused by an accumulation of effector and memory
      T cells. These data identify Blimp-1 as an essential regulator of T cell
      homeostasis and suggest that Blimp-1 regulates both B cell and T cell
      differentiation.

PMID- 16565721
TI  - Transcriptional repressor Blimp-1 regulates T cell homeostasis and function.
AB  - The B lymphocyte-induced maturation protein 1 (Blimp-1) transcriptional repressor
      is required for terminal differentiation of B lymphocytes. Here we document a
      function for Blimp-1 in the T cell lineage. Blimp-1-deficient thymocytes showed
      decreased survival and Blimp-1-deficient mice had more peripheral effector T
      cells. Mice lacking Blimp-1 developed severe colitis as early as 6 weeks of age,
      and Blimp-1-deficient regulatory T cells were defective in blocking the
      development of colitis. Blimp-1 mRNA expression increased substantially in
      response to T cell receptor stimulation. Compared with wild-type CD4(+) T cells,
      Blimp-1-deficient CD4(+) T cells proliferated more and produced excess
      interleukin 2 and interferon-gamma but reduced interleukin 10 after T cell
      receptor stimulation. These results emphasize a crucial function for Blimp-1 in
      controlling T cell homeostasis and activation.

PMID- 16565722
TI  - Reactive oxygen species act through p38 MAPK to limit the lifespan of
      hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) undergo self-renewing cell divisions and maintain
      blood production for their lifetime. Appropriate control of HSC self-renewal is
      crucial for the maintenance of hematopoietic homeostasis. Here we show that
      activation of p38 MAPK in response to increasing levels of reactive oxygen
      species (ROS) limits the lifespan of HSCs in vivo. In Atm(-/-) mice, elevation of
      ROS levels induces HSC-specific phosphorylation of p38 MAPK accompanied by a
      defect in the maintenance of HSC quiescence. Inhibition of p38 MAPK rescued ROS
      induced defects in HSC repopulating capacity and in the maintenance of HSC
      quiescence, indicating that the ROS-p38 MAPK pathway contributes to exhaustion of
      the stem cell population. Furthermore, prolonged treatment with an antioxidant or
      an inhibitor of p38 MAPK extended the lifespan of HSCs from wild-type mice in
      serial transplantation experiments. These data show that inactivation of p38 MAPK
      protects HSCs against loss of self-renewal capacity. Our characterization of
      molecular mechanisms that limit HSC lifespan may lead to beneficial therapies for
      human disease.

PMID- 16565723
TI  - Role of matrix metalloproteinases in delayed cortical responses after stroke.
AB  - Matrix metalloproteinases (MMPs) are zinc-endopeptidases with multifactorial
      actions in central nervous system (CNS) physiology and pathology. Accumulating
      data suggest that MMPs have a deleterious role in stroke. By degrading
      neurovascular matrix, MMPs promote injury of the blood-brain barrier, edema and
      hemorrhage. By disrupting cell-matrix signaling and homeostasis, MMPs trigger
      brain cell death. Hence, there is a movement toward the development of MMP
      inhibitors for acute stroke therapy. But MMPs may have a different role during
      delayed phases after stroke. Because MMPs modulate brain matrix, they may mediate
      beneficial plasticity and remodeling during stroke recovery. Here, we show that
      MMPs participate in delayed cortical responses after focal cerebral ischemia in
      rats. MMP-9 is upregulated in peri-infarct cortex at 7-14 days after stroke and
      is colocalized with markers of neurovascular remodeling. Treatment with MMP
      inhibitors at 7 days after stroke suppresses neurovascular remodeling, increases
      ischemic brain injury and impairs functional recovery at 14 days. MMP processing
      of bioavailable VEGF may be involved because inhibition of MMPs reduces
      endogenous VEGF signals, whereas additional treatment with exogenous VEGF
      prevents MMP inhibitor-induced worsening of infarction. These data suggest that,
      contrary to MMP inhibitor therapies for acute stroke, strategies that modulate
      MMPs may be needed for promoting stroke recovery.

PMID- 16565724
TI  - Human sebaceous tumors harbor inactivating mutations in LEF1.
AB  - We found that one-third of human sebaceous tumors examined had double-nucleotide
      substitutions in the same LEF1 allele, irrespective of DNA mismatch repair
      status. The mutations impaired both LEF1 binding to beta-catenin and
      transcriptional activation, and are the first tumor-associated mutations that
      inactivate Wnt signaling. Mutant LEF1 not only inhibited expression of beta
      catenin target genes but also stimulated expression of sebocyte markers,
      suggesting that it may determine the differentiated characteristics of sebaceous
      tumors.

PMID- 16565725
TI  - Structure and mechanism of a bacterial beta-glucosaminidase having O-GlcNAcase
      activity.
AB  - O-GlcNAc is an abundant post-translational modification of serine and threonine
      residues of nucleocytoplasmic proteins. This modification, found only within
      higher eukaryotes, is a dynamic modification that is often reciprocal to
      phosphorylation. In a manner analogous to phosphatases, a glycoside hydrolase
      termed O-GlcNAcase cleaves O-GlcNAc from modified proteins. Enzymes with high
      sequence similarity to human O-GlcNAcase are also found in human pathogens and
      symbionts. We report the three-dimensional structure of O-GlcNAcase from the
      human gut symbiont Bacteroides thetaiotaomicron both in its native form and in
      complex with a mimic of the reaction intermediate. Mutagenesis and kinetics
      studies show that the bacterial enzyme, very similarly to its human counterpart,
      operates via an unusual 'substrate-assisted' catalytic mechanism, which will
      inform the rational design of enzyme inhibitors.

PMID- 16565726
TI  - Ca(2+)-synaptotagmin directly regulates t-SNARE function during reconstituted
      membrane fusion.
AB  - In nerve terminals, exocytosis is mediated by SNARE proteins and regulated by
      Ca(2+) and synaptotagmin-1 (syt). Ca(2+) promotes the interaction of syt with
      anionic phospholipids and the target membrane SNAREs (t-SNAREs) SNAP-25 and
      syntaxin. Here, we have used a defined reconstituted fusion assay to determine
      directly whether syt-t-SNARE interactions couple Ca(2+) to membrane fusion by
      comparing the effects of Ca(2+)-syt on neuronal (SNAP-25, syntaxin and
      synaptobrevin) and yeast (Sso1p, Sec9c and Snc2p) SNAREs. Ca(2+)-syt aggregated
      neuronal and yeast SNARE liposomes to similar extents via interactions with
      anionic phospholipids. However, Ca(2+)-syt was able to bind and stimulate fusion
      mediated by only neuronal SNAREs and had no effect on yeast SNAREs. Thus, Ca(2+)
      syt regulates fusion through direct interactions with t-SNAREs and not solely
      through aggregation of vesicles. Ca(2+)-syt drove assembly of SNAP-25 onto
      membrane-embedded syntaxin, providing direct evidence that Ca(2+)-syt alters t
      SNARE structure.

PMID- 16565728
TI  - Transdermal protein delivery by a coadministered peptide identified via phage
      display.
AB  - Efficient transdermal drug delivery of large hydrophilic drugs is challenging.
      Here we report that the short synthetic peptide, ACSSSPSKHCG, identified by in
      vivo phage display, facilitated efficient transdermal protein drug delivery
      through intact skin. Coadministration of the peptide and insulin to the abdominal
      skin of diabetic rats resulted in elevated systemic levels of insulin and
      suppressed serum glucose levels for at least 11 h. Significant systemic
      bioavailability of human growth hormone was also achieved when topically
      coadministered with the peptide. The transdermal-enhancing activity of the
      peptide was sequence specific and dose dependent, did not involve direct
      interaction with insulin and enabled penetration of insulin into hair follicles
      beyond a depth of 600 microm. Time-lapse studies suggested that the peptide
      creates a transient opening in the skin barrier to enable macromolecular drugs to
      reach systemic circulation.

PMID- 16565727
TI  - Generation of cloned transgenic pigs rich in omega-3 fatty acids.
AB  - Meat products are generally low in omega-3 (n-3) fatty acids, which are
      beneficial to human health. We describe the generation of cloned pigs that
      express a humanized Caenorhabditis elegans gene, fat-1, encoding an n-3 fatty
      acid desaturase. The hfat-1 transgenic pigs produce high levels of n-3 fatty
      acids from n-6 analogs, and their tissues have a significantly reduced ratio of n
      6/n-3 fatty acids (P < 0.001).

PMID- 16565729
TI  - S-nitrosylation of cysteine 289 of the AT1 receptor decreases its binding
      affinity for angiotensin II.
AB  - 1. Nitric oxide (NO) is known to affect the properties of various proteins via
      the S-nitrosylation of cysteine residues. This study evaluated the direct effects
      of the NO donor sodium nitroprusside (SNP) on the pharmacological properties of
      the AT1 receptor for angiotensin II expressed in HEK-293 cells. 2. SNP dose
      dependently decreased the binding affinity of the AT1 receptor without affecting
      its total binding capacity. This modulatory effect was reversed within 5 min of
      removing SNP. 3. The effect of SNP was not modified in the presence of the G
      protein uncoupling agent GTPgammaS or the soluble guanylyl cyclase inhibitor 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. 4. The binding properties of a mutant
      AT1 receptor in which all five cysteine residues within the transmembrane domains
      had been replaced by serine was not affected by SNP. Systematic analysis of
      mutant AT1 receptors revealed that cysteine 289 conferred the sensitivity to SNP.
      5. These results suggest that NO decreased the binding affinity of the AT1
      receptor by S-nitrosylation of cysteine 289. This modulatory mechanism may be
      particularly relevant in pathophysiological situations where the beneficial
      effects of NO oppose the deleterious effects of angiotensin II.

PMID- 16565730
TI  - Pharmacological assessment of the duration of action of glycopyrrolate vs
      tiotropium and ipratropium in guinea-pig and human airways.
AB  - 1. Our study was aimed at investigating the duration of the bronchodilator action
      of the antimuscarinc drug glycopyrrolate compared to tiotropium and ipratropium.
      In the guinea-pig isolated trachea, the time (t1/2) necessary for a contractile
      response to carbachol (0.3 microM) to return to 50% recovery after washout of the
      antagonist was studied. The offset of the antagonist effect of glycopyrrolate,
      tiotropium and ipratropium (10 nM each) was t1/2 = 4.0 +/- 0.5, > 4.5 and 0.5 +/-
      0.1 h, respectively. At 4.5 h from the washout of the antagonist, the recovery of
      the response to carbachol was 50 +/- 8, 10 +/- 4 and 70 +/- 7%, respectively. 2.
      In the human isolated bronchus, the offset of the bronchodilator effects of
      glycopyrrolate (3 nM), tiotropium (1 nM) and ipratropium (10 nM) was t1/2 = 3.7
      +/- 0.2; > 6 and 3.0 +/- 0.2 h, respectively. At 6.0 h from the washout of the
      antagonist, the recovery of the response to carbachol (1 microM) was 101 +/- 10,
      27 +/- 3 and 110 +/- 10%, respectively. 4. In anaesthetized guinea-pigs,
      acetylcholine-induced bronchoconstriction was markedly reduced by intratracheal
      instillation of glycopyrrolate (3 nmol kg(-1); 88.1 +/- 4% inhibition),
      tiotropium (1.3 nmol kg(-1); 86.2 +/- 5% inhibition) or ipratropium (1.45 nmol
      kg(-1); 88.1 +/- 10% inhibition). These inhibitory effects assessed 3 or 24 h
      after antagonist administration were reduced to 69.9 +/- 5 and 29.7 +/- 6%; 28.3
      +/- 5 and 14.2 +/- 5% for glycopyrrolate and ipratropium, respectively, whereas
      they remained stable (83.5 +/- 4; 70.6 +/- 6) for tiotropium. The residual
      inhibitory effect of glycopyrrolate was also assessed at 16 h from
      administration, and proved to be as low as that found at 24 h (31.2 +/- 10 vs
      29.7 +/- 6%, respectively). 5. In conclusion, glycopyrrolate-induced
      bronchodilation has a longer duration than that of ipratropium, but less than
      that of tiotropium. The efficacy of a possible glycopyrrolate-based therapy for
      asthma or chronic obstructive pulmonary disease given once-a-day is not
      guaranteed by the present investigation.

PMID- 16565731
TI  - Involvement of Rho kinase and protein kinase C in carbachol-induced calcium
      sensitization in beta-escin skinned rat and guinea-pig bladders.
AB  - 1. The signal transduction pathways involved in carbachol (CCh)-induced calcium
      sensitization in beta-escin permeabilized rat and guinea-pig bladder smooth
      muscles were investigated and the results were compared with guinea-pig taenia
      caecum. 2. Calcium contractions elicited cumulatively (pCa 7.5-5) in the presence
      of calmodulin were significantly increased in all three tissues when CCh (50
      microM) was added to the medium. 3. Under constant [Ca2+]i conditions (pCa 6),
      calmodulin (1 microM) and then GTP (100 microM) initiated significant
      contractions. CCh (50 microM) added to the bath caused a further contraction in
      all three tissues - calcium sensitization. This sensitization was significantly
      inhibited by atropine (50 microM). 4. The incubation of the tissues with the IP3
      receptor blocker 2-APB (30 microM) reduced the subsequent development of calcium
      sensitization by CCh in rat bladder but did not affect it in guinea-pig bladder
      and taenia ceacum. 5. The Rho kinase (ROK) inhibitor Y-27632 (5 microM) added in
      the presence of CCh reversed the calcium sensitization in rat bladder, whereas a
      transient contraction followed by a relaxation to a level not significantly
      different from the CCh contraction was seen in both guinea-pig bladder and taenia
      caecum. Y-27632 (1 microM) continuously present significantly inhibited the CCh
      induced Ca2+ sensitization in rat bladder but not in guinea-pig bladder or taenia
      caecum. 6. In the presence of cyclopiazonic acid (CPA) (1 microM) and calmodulin
      (1 microM), Y-27632 (5 microM) did not change the calcium response curve (3 x 10(
      7)-10(-5) M) in rat bladder but increased the contractile responses significantly
      in both guinea-pig bladder and taenia caecum. 7. The protein kinase C (PKC)
      inhibitor GF 109203X (5 microM) added in the presence of CCh inhibited the
      calcium sensitization induced by this muscarinic agonist in all three tissues in
      different ratios. 8. In conclusion, muscarinic receptor activation induces
      calcium sensitization in rat and guinea-pig detrusor smooth muscles but there are
      differences in their pathways.

PMID- 16565732
TI  - Platelets accelerate gastric ulcer healing through presentation of vascular
      endothelial growth factor.
AB  - 1. Platelets contain an array of growth factors that can modulate healing
      processes, including both pro- (e.g., vascular endothelial growth factor (VEGF))
      and antiangiogenic (e.g., endostatin) factors. Previous studies have shown that
      circulating platelets contribute significantly to gastric ulcer healing, acting
      as a delivery system for these growth factors to the site of injury. In this
      study, we examined the effects of orally administered human platelets on the
      healing of gastric ulcers in rats, and determined the contribution of VEGF and
      endostatin to healing in this model. 2. Twice-daily administration of human
      platelets significantly accelerated ulcer healing, but platelet-poor plasma
      (PPP), lysed platelets and serum failed to produce this effect. There was no
      correlation between ulcer healing and the levels of VEGF or endostatin in serum,
      PPP or platelet-rich plasma (PRP). 3. Accelerated ulcer healing could not be
      produced by oral administration of the angiogenic factors themselves, at
      concentrations matching those in PRP. 4. The accelerated healing induced by
      platelets could be reversed by immuno-neutralization of VEGF. In contrast, immuno
      neutralization of endostatin did not affect PRP-induced ulcer healing. 5. These
      studies indicate that VEGF released from platelets accounts for the accelerated
      healing of gastric ulcers. However, as intact (rather than lysed) platelets were
      required for the accelerated healing, the presentation of VEGF by the platelet at
      the site of injury appears to be crucial for enhancement of the healing process.

PMID- 16565734
TI  - Non-myeloablative allogeneic stem cell transplant in a patient with refractory
      systemic lupus erythematosus.

PMID- 16565733
TI  - Blockade of IKs by HMR 1556 increases the reverse rate-dependence of
      refractoriness prolongation by dofetilide in isolated rabbit ventricles.
AB  - 1. The rate-dependent contributions of the rapid and slow components of the
      cardiac delayed rectifier K+ current (IKr and IKs, respectively) to
      repolarization are not fully understood. It is unclear whether the addition of
      IKs block will attenuate reverse rate-dependence seen after IKr block. 2. The
      individual and combined electrophysiological effects of selective IKr and IKs
      blockers, dofetilide and HMR 1556, respectively, were evaluated using Langendorff
      perfused rabbit hearts. Monophasic action potential duration at 90%
      repolarization (MAPD90) and ventricular effective refractory period (VERP) were
      determined at cycle lengths (CLs) of 200-500 ms (at 50 ms intervals). 3.
      Dofetilide (1-100 nM) prolonged MAPD90 in a concentration-dependent manner (P <
      0.001, n = 6) with reverse rate-dependence (P < 0.0001). In contrast, HMR 1556
      (10-240 nM) alone did not prolong MAPD90. However, in the presence of 7.5 nM
      dofetilide, HMR 1556 (100 nM) increased the extent of reverse rate-dependence by
      further prolonging MAPD90 at CLs of 400, 450 and 500 ms (P < 0.05, n = 9) and, to
      a lesser extent, at shorter CLs (e.g. by 17 +/- 4 ms at CL 500 vs 2 +/- 3 ms at
      CL 200 ms). 4. Effects of dofetilide and HMR 1556 on VERP were similar to those
      on MAPD90. The slope of the VERP vs CL relation was steeper after the combination
      (0.081 +/- 0.013) than after dofetilide alone (0.028 +/- 0.018, P < 0.01, n = 9).
      5. Blockade of rabbit IKs increased reverse rate-dependence of IKr block.

PMID- 16565735
TI  - Reduced-intensity allogeneic haemopoietic stem cell transplantation induces
      durable responses in patients with chronic B-lymphoproliferative disorders.
AB  - Thirty-six patients with chronic B-lymphoproliferative disorders (B-LPD)
      underwent reduced-intensity allogeneic transplantation (RIT) from HLA-identical
      related donors. Diagnoses included follicular (n=17), mantle cell (n=9) and small
      lymphocytic lymphoma (n=2), and chronic lymphocytic leukaemia (n=8). Median age
      at transplant was 51 years (range, 30-66) and time from diagnosis was 3.4 years
      (range, 0.3-9.5). At transplant, 28% were in CR, 36% were in PR and 36% were
      chemorefractory. Conditioning therapy included fludarabine and either
      cyclophosphamide (n=27) or melphalan (n=9). Graft-versus-host disease (GVHD)
      prophylaxis consisted of cyclosporin (CsA)/methotrexate (n=21), CsA/mycophenolate
      mofetil (n=13) or CsA alone (n=2). Eight patients died owing to acute GVHD (n=3),
      infection in association with chronic GVHD (n=4) and intra-abdominal bleeding
      (n=1). Treatment-related mortality was 8% at day 100, and 17 and 20% at one and
      two years, respectively. The cumulative incidence of grade II-IV acute GVHD was
      58%, whereas limited and extensive chronic GVHD occurred in 25 and 56%,
      respectively. No patient has relapsed or progressed. At a median follow-up of 48
      months, overall survival probability is 80% (95% CI, 67-93%). We confirm that RIT
      in chronic B-LPD can result in high and durable CR rates but with significant
      incidences of acute and chronic GVHD.

PMID- 16565736
TI  - T-cell-depleted stem cell boost for the treatment of autoimmune haemolytic
      anaemia after T-cell-depleted allogeneic bone marrow transplantation complicated
      by adenovirus infection.

PMID- 16565737
TI  - High-dose chemotherapy and autologous peripheral blood stem cell transplantation
      for primary breast cancer refractory to neoadjuvant chemotherapy.
AB  - The role of high-dose chemotherapy (HDCT) in patients with refractory breast
      cancer is not well established. Forty-two female patients (median age of 46
      years) with breast cancer refractory to neoadjuvant chemotherapy received HDCT
      (cyclophosphamide, carmustine and thiotepa) supported by an autologous peripheral
      blood stem cells transplant. Their disease had been refractory (defined as less
      than partial response) to one (18 patients) or two (24 patients) regimens of
      neoadjuvant chemotherapy. Twenty-nine patients had surgery before HDCT. The best
      response after surgery, HDCT, and radiation therapy was assessed 60 days after
      transplantation. Thirty patients had complete remission, eight had a PR, one had
      a minor response, and three had progressive disease. In seven of 13 patients
      whose disease was inoperable before HDCT, it became operable. After a median
      follow-up of 42 months, 21 patients were alive, and 15 remained disease free.
      Five-year overall survival (OS) was 57% (CI, 50-64%), and the estimated 5-year
      progression-free survival was 40% (CI, 32-48%). Both OS and PFS were better in
      patients whose disease became operable after chemotherapy than in those whose
      disease remained inoperable. A randomized study is warranted in this patient
      population.

PMID- 16565739
TI  - Impact of high-resolution matching in allogeneic unrelated donor stem cell
      transplantation in Switzerland.
AB  - It is currently unknown what degree of human leukocyte antigen (HLA)-mismatching
      is acceptable in unrelated donor hematopoietic stem cell transplantation (UD
      HSCT). Mismatches at some loci may be more permissive than others. We have
      analyzed the effect of high-resolution HLA-matching on outcome of all 214
      consecutive recipients of UD-HSCT carried out in Switzerland. All typing was by
      the Swiss reference laboratory. Donor-recipient pairs were HLA-10/10 matched
      (n=130) or mismatched for either HLA-A/-B/-DRB1/multiple loci (n=33; (HLA-A/
      B=10); (-DRB1=8); (multiple=15)); HLA-C (n=29) or HLA-DQ/-DRB3 (n=22; (DQ=16); (
      DRB1=6)). The median follow-up was 32 months. Survival probabilities (+/-95%
      confidence interval) at 3 years were 57 (+/-10)% for recipients of HLA 10/10
      matched transplants, 53 (+/-22)% for recipients of HLA-DQ/-DRB3-mismatched
      transplants, 44 (+/-20)% for recipients of HLA-C-mismatched transplants and 0%
      for recipients of transplants mismatched at HLA-A/-B/-DRB1/multiple loci
      (P<0.0001). In multivariate analyses, HLA compatibility was the variable most
      significantly associated with survival and treatment-related mortality. We found
      important differences in survival in recipients of UD-HSCT with best results for
      transplants from 10/10 matched donors. Single mismatches at HLA-DQ/-DRB3 were
      well tolerated, mismatches at HLA-C had intermediate results and mismatches at
      HLA-A/-B/-DRB1/multiple loci resulted in poor survival.

PMID- 16565738
TI  - Long-term outcome of high-dose melphalan and autologous stem cell transplantation
      for AL amyloidosis.
AB  - Light chain (AL) amyloidosis is the result of a clonal plasma cell expansion, in
      which amyloidogenic monoclonal light chains deposit in various tissues resulting
      in organ dysfunction and organ failure. The median survival of patients with AL
      amyloidosis without therapy is 10-14 months. Several phase II studies report
      haematological and clinical remission in up to 50% of patients after high-dose
      melphalan and autologous stem cell transplantation. We analysed retrospectively
      the long-term outcome of 19 patients treated in this way between August/1996 and
      December/2001. We observed a relatively high treatment-related mortality of 26%,
      but 12 patients (63%) were high-risk candidates. Eight patients (42%) surviving
      longer than 100 days achieved haematological remission and long-term survival,
      whereas 6 (32%) obtained no clear benefit from high-dose therapy. However, 62% of
      patients survived beyond 2 years and the median survival from transplant was 48
      months (range 0-104 months).

PMID- 16565740
TI  - Major salivary gland damage in allogeneic hematopoietic progenitor cell
      transplantation assessed by scintigraphic methods.
AB  - Salivary gland dysfunction is a common sequela of hematopoietic progenitor cell
      transplantation (HPCT). The investigation of major salivary gland dysfunction
      with sodium pertechnetate scintigraphy is a non-invasive method that provides
      images of the parotid and submandibular glands. In this prospective trial, 20
      HPCT patients were submitted to scintigraphic study with 99mTc-pertechenate and
      67Ga in order to evaluate the major salivary glands early involvement following
      HPCT. Major salivary glands were evaluated prior to HCPT as well as at Days +30,
      +60 and +100 post transplant. Major salivary glands uptake and clearance of 99mTc
      pertechenate results did not demonstrate any functional differences between pre-
      versus post transplant periods. Results of the 67Ga scan revealed inflammatory
      infiltration following HPCT, primarily in submandibular glands, suggest a
      persistent involvement of major salivary glands up to Day +100 after HPCT.

PMID- 16565741
TI  - Effect of interleukin-15 on effector and regulatory function of anti-CD3/anti
      CD28-stimulated CD4(+) T cells.
AB  - Autologous transfer of anti-CD3/anti-CD28 (CD3/CD28)-activated CD4(+) T cells may
      benefit patients receiving autologous stem cell transplant with severe CD4
      lymphopenia. Interleukin (IL)-15, an IL-2-like cytokine that promotes T cell
      survival may enhance immune reconstitution in conjunction with adoptive
      immunotherapy. We investigated the effect of IL-15 on effector and regulatory
      function of CD3/CD28-activated CD4(+) T cells. IL-15 upregulated CD45RO and CD25
      whereas it down regulated CD62L expression of CD3/CD28-stimulated CD4(+) T cells.
      Both type 1 (IFN-gamma, tumor necrosis factor (TNF)-alpha) and type 2 (IL-5 and
      IL-10) production by CD3/CD28-activated CD4(+) T cells was further enhanced by IL
      15. Co-culture experiments revealed that CD3/CD28-activated CD4(+) T cells down
      regulated proliferation of autologous peripheral blood lymphocytes (PBLs) and
      CD8(+) PBL subsets upon TCR ligation, a contact-dependent effect that was further
      enhanced by pretreatment with IL-15. Flow cytometric analysis of cell mixture
      with carboxyfluorescein diacetate succinimidyl ester and Annexin-V-PE staining
      revealed that CD3/CD28+IL-15-activated CD4(+) T cells showed increased apoptosis
      over CD4(+) T cells stimulated with CD3/CD28 alone. Taken together, pretreatment
      of CD3/CD28-activated CD4(+) T cells with IL-15 may increase regulatory function
      but may aggravate activation-induced apoptosis of CD3/CD28 CD4(+) T cells.

PMID- 16565742
TI  - Individualized exercise program for the treatment of severe fatigue in patients
      after allogeneic hematopoietic stem-cell transplant: a pilot study.
AB  - Chronic cancer-related fatigue in otherwise asymptomatic post-allogeneic
      hematopoietic stem cell transplant (HSCT) patients is common and debilitating.
      This pilot study investigated whether patients with no clinical or psychological
      abnormalities but severe fatigue would respond to an individually adapted aerobic
      exercise program. Participants were 12 patients (eight male, and four female
      patients), median age 47 years and 41 months post-HSCT with a variety of
      hematopoietic cancer diagnoses. All underwent a 12-week individualized mild
      aerobic exercise program, preceded by a 4-week introduction and baseline testing
      phase. Psychological measures included fatigue, mood and depression. Exercise
      related physiological outcomes included power output at ventilatory threshold 2
      (VT2) and associated changes in stroke volume, heart rate, blood lactate
      concentration and ratings of perceived exertion. Patients were assessed for
      fatigue before, immediately after and at 3, 6, 9 and 12 months post-program.
      Significant improvements were found on both measures of fatigue (both P<0.001),
      with a very large effect size of 1.82 on the The Functional Assessment of Cancer
      Therapy - Fatigue Module, which were maintained over the follow-up period.
      Exercise testing revealed a mean increase (P<0.001) of 28% in power output at VT2
      with an increase (P<0.001) in stroke volume and a decrease (P<0.001) in heart
      rate, blood lactate and perceived exertion at pre-intervention VT2 power output.

PMID- 16565743
TI  - Maintenance thalidomide following single cycle autologous peripheral blood stem
      cell transplant in patients with multiple myeloma.
AB  - Although autologous stem cell transplant is an effective therapy for patients
      with multiple myeloma and extends progression-free survival (PFS) and overall
      survival (OS), patients show a continued pattern of recurrent disease. Twenty
      nine patients were enrolled in a phase II study investigating the tolerability
      and efficacy of maintenance thalidomide following single autologous peripheral
      blood stem cell transplant. Six to eight weeks after transplant, patients were
      started on maintenance thalidomide at 50 mg a day. The dose was gradually
      escalated to a target dose of 400 mg a day and continued until disease
      progression or 6 months after achieving complete remission (CR) for a maximum
      total duration of 18 months. At 6 months, 13 patients (45%) achieved CR or near
      complete remission (positive immunofixation without any evidence of disease). The
      estimated 2-year OS was 83% and PFS was 49%. Median tolerated dose of thalidomide
      was 200 mg a day. In conclusion, thalidomide as maintenance therapy is feasible
      and may improve outcome after single autologous stem cell transplant.

PMID- 16565744
TI  - Therapy for severe refractory acute graft-versus-host disease with basiliximab, a
      selective interleukin-2 receptor antagonist.
AB  - Basiliximab is a chimeric monoclonal antibody that binds to the alpha chain of IL
      2R on activated cytotoxic T-cells, inhibiting lymphocyte proliferation. We report
      34 patients with refractory acute GVHD (grade III-IV) who received basiliximab
      from December 1998 to October 2003. Adults received 40 mg weekly (2-3 doses) and
      children received half of this dose. Median age was 13 years. Twenty-five donors
      were unrelated. The stem cell source was bone marrow in 30 and cord blood in
      four. Complete responses were seen in 27/32 patients (84%) with skin, 12/25 (48%)
      with gut and 6/23 (26%) with liver GVHD. Median duration of response was 38 days
      (5-1103). Overall survival at 5 years was 20%. Eleven patients (32%) are alive.
      The main causes of death were CMV (n=4), fungus (n=6), sepsis (n=8), hemorrhage
      (n=2), and relapse (n=2). Graft-versus-host disease flares were observed in 14
      patients (41%), half being rescued by other therapies. In conclusion, basiliximab
      was able to induce complete responses in patients with refractory acute GVHD.
      Prospective studies are necessary to evaluate the optimal treatment schedule.

PMID- 16565747
TI  - Fast and effective characterization for classification and similarity searches of
      2D and 3D spatial region data.
AB  - We propose a method for characterizing spatial region data. The method
      efficiently constructs a k-dimensional feature vector using concentric spheres in
      3D (circles in 2D) radiating out of a region's center of mass. These signatures
      capture structural and internal volume properties. We evaluate our approach by
      performing experiments on classification and similarity searches, using
      artificial and real datasets. To generate artificial regions we introduce a
      region growth model. Similarity searches on artificial data demonstrate that our
      technique, although straightforward, compares favorably to mathematical
      morphology, while being two orders of magnitude faster. Experiments with real
      datasets show its effectiveness and general applicability.

PMID- 16565745
TI  - Control of daily transcript oscillations in Drosophila by light and the circadian
      clock.
AB  - The transcriptional circuits of circadian clocks control physiological and
      behavioral rhythms. Light may affect such overt rhythms in two ways: (1) by
      entraining the clock circuits and (2) via clock-independent molecular pathways.
      In this study we examine the relationship between autonomous transcript
      oscillations and light-driven transcript responses. Transcript profiles of wild
      type and arrhythmic mutant Drosophila were recorded both in the presence of an
      environmental photocycle and in constant darkness. Systematic autonomous
      oscillations in the 12- to 48-h period range were detectable only in wild-type
      flies and occurred preferentially at the circadian period length. However, an
      extensive program of light-driven expression was confirmed in arrhythmic mutant
      flies. Many light-responsive transcripts are preferentially expressed in the
      compound eyes and the phospholipase C component of phototransduction, NORPA (no
      receptor potential), is required for their light-dependent regulation. Although
      there is evidence for the existence of multiple molecular clock circuits in
      cyanobacteria, protists, plants, and fungi, Drosophila appears to possess only
      one such system. The sustained photic expression responses identified here are
      partially coupled to the circadian clock and may reflect a mechanism for flies to
      modulate functions such as visual sensitivity and synaptic transmission in
      response to seasonal changes in photoperiod.

PMID- 16565748
TI  - Congo red interaction with alpha-proteins.
AB  - The ability of Congo red to form complexes with alpha-proteins, human growth
      hormone and human interferon-alpha2b, was found by absorption difference
      spectroscopy. A human growth hormone-Congo red complex was isolated by gel
      permeation chromatography, and its visible absorption spectrum was registered in
      comparison to free dye. The ability of Congo red to induce dimerization of human
      growth hormone was demonstrated using chemical cross-linking agents 1,3,5
      triacryloyl-hexahydro-s-triazine and ethylene glycol bis(succinimidylsuccinate).

PMID- 16565746
TI  - Assumption-free estimation of heritability from genome-wide identity-by-descent
      sharing between full siblings.
AB  - The study of continuously varying, quantitative traits is important in
      evolutionary biology, agriculture, and medicine. Variation in such traits is
      attributable to many, possibly interacting, genes whose expression may be
      sensitive to the environment, which makes their dissection into underlying
      causative factors difficult. An important population parameter for quantitative
      traits is heritability, the proportion of total variance that is due to genetic
      factors. Response to artificial and natural selection and the degree of
      resemblance between relatives are all a function of this parameter. Following the
      classic paper by R. A. Fisher in 1918, the estimation of additive and dominance
      genetic variance and heritability in populations is based upon the expected
      proportion of genes shared between different types of relatives, and explicit,
      often controversial and untestable models of genetic and non-genetic causes of
      family resemblance. With genome-wide coverage of genetic markers it is now
      possible to estimate such parameters solely within families using the actual
      degree of identity-by-descent sharing between relatives. Using genome scans on
      4,401 quasi-independent sib pairs of which 3,375 pairs had phenotypes, we
      estimated the heritability of height from empirical genome-wide identity-by
      descent sharing, which varied from 0.374 to 0.617 (mean 0.498, standard deviation
      0.036). The variance in identity-by-descent sharing per chromosome and per genome
      was consistent with theory. The maximum likelihood estimate of the heritability
      for height was 0.80 with no evidence for non-genetic causes of sib resemblance,
      consistent with results from independent twin and family studies but using an
      entirely separate source of information. Our application shows that it is
      feasible to estimate genetic variance solely from within-family segregation and
      provides an independent validation of previously untestable assumptions. Given
      sufficient data, our new paradigm will allow the estimation of genetic variation
      for disease susceptibility and quantitative traits that is free from confounding
      with non-genetic factors and will allow partitioning of genetic variation into
      additive and non-additive components.

PMID- 16565749
TI  - Application of alicyclic beta-amino acids in peptide chemistry.
AB  - The self-organizing beta-peptides have attracted considerable interest in the
      fields of foldamer chemistry and biochemistry. These compounds exhibit various
      stable secondary structure motifs that can be exploited to construct biologically
      active substances and nanostructured tertiary structures. The secondary
      structures can be controlled via the beta-amino acid sequence, and cyclic beta
      amino acid residues play a crucial role in the design. The most important
      procedures for the preparation of cyclic beta-amino acid monomers and peptides
      are discussed in this tutorial review. Besides the secondary structure design
      principles, the methods of folded structure detection are surveyed.

PMID- 16565750
TI  - Automotive fuels and internal combustion engines: a chemical perspective.
AB  - Commercial transportation fuels are complex mixtures containing hundreds or
      thousands of chemical components, whose composition has evolved considerably
      during the past 100 years. In conjunction with concurrent engine advancements,
      automotive fuel composition has been fine-tuned to balance efficiency and power
      demands while minimizing emissions. Pollutant emissions from internal combustion
      engines (ICE), which arise from non-ideal combustion, have been dramatically
      reduced in the past four decades. Emissions depend both on the engine operating
      parameters (e.g. engine temperature, speed, load, A/F ratio, and spark timing)
      and the fuel. These emissions result from complex processes involving
      interactions between the fuel and engine parameters. Vehicle emissions are
      comprised of volatile organic compounds (VOCs), CO, nitrogen oxides (NO(x)), and
      particulate matter (PM). VOCs and NO(x) form photochemical smog in urban
      atmospheres, and CO and PM may have adverse health impacts. Engine hardware and
      operating conditions, after-treatment catalysts, and fuel composition all affect
      the amount and composition of emissions leaving the vehicle tailpipe. While
      engine and after-treatment effects are generally larger than fuel effects, engine
      and after-treatment hardware can require specific fuel properties. Consequently,
      the best prospects for achieving the highest efficiency and lowest emissions lie
      with optimizing the entire fuel-engine-after-treatment system. This review
      provides a chemical perspective on the production, combustion, and environmental
      aspects of automotive fuels. We hope this review will be of interest to workers
      in the fields of chemical kinetics, fluid dynamics of reacting flows, atmospheric
      chemistry, automotive catalysts, fuel science, and governmental regulations.

PMID- 16565753
TI  - Recent progress on switchable rotaxanes.
AB  - Switchable rotaxanes are currently attracting considerable attention from
      chemists, physicists and materials scientists because of their potential to
      perform relative inter-component positional changes in response to external
      stimuli and the potential applications in the fields such as molecular machines,
      molecular switches, molecular logic gates and memory devices. This tutorial
      review summarizes recent work on switchable rotaxanes and their potential
      applications.

PMID- 16565751
TI  - Systematizing structural motifs and nomenclature in 1,n'-disubstituted ferrocene
      peptides.
AB  - Ferrocene peptide conjugates display an array of structural features including
      helical ferrocene based chirality and a number of different intramolecular
      hydrogen bonding patterns. In this tutorial review we present a rigorous
      nomenclature for these systems, followed by a section that summarises and
      categorises the structures known to date. The issues discussed herein are of
      general relevance for all metallocene-based chiral transition metal catalysts and
      peptide turn mimetics.

PMID- 16565752
TI  - Imidazolium receptors for the recognition of anions.
AB  - This tutorial review covers imidazolium receptors for anion recognition according
      to their topological and structural classification, and includes benzene
      tripodal, cyclophane and calix-imidazolium, fluorescent imidazolium, ferrocenyl
      imidazolium, cavitand and calixarene, and polymeric imidazolium systems.

PMID- 16565754
TI  - Organically-templated metal sulfates, selenites and selenates.
AB  - The literature on inorganic open-framework materials abounds in the synthesis and
      characterization of metal silicates, phosphates and carboxylates. Most of these
      materials have an organic amine as the template. In the last few years, it has
      been shown that anions such as sulfate, selenite and selenate can also be
      employed to obtain organically templated open-framework materials. This tutorial
      review provides an up-to-date survey of organically templated metal sulfates,
      selenites and selenates, prepared under hydrothermal conditions. The discussion
      includes one-, two-, and three-dimensional structures of these materials, many of
      which possess open architectures. The article should be useful to practitioners
      of inorganic and materials chemistry, besides students and teachers. The article
      serves to demonstrate how most oxy-anions can be used to build complex structures
      with metal-oxygen polyhedra.

PMID- 16565755
TI  - Re-defining neurological syndromes: the genotype meets the phenotype.

PMID- 16565756
TI  - Relationship between item difficulty and discrimination indices in true/false
      type multiple choice questions of a para-clinical multidisciplinary paper.
AB  - INTRODUCTION: This paper reports the relationship between the difficulty level
      and the discrimination power of true/false-type multiple-choice questions (MCQs)
      in a multidisciplinary paper for the para-clinical year of an undergraduate
      medical programme. MATERIALS AND METHODS: MCQ items in papers taken from Year II
      Parts A, B and C examinations for Sessions 2001/02, and Part B examinations for
      2002/03 and 2003/04, were analysed to obtain their difficulty indices and
      discrimination indices. Each paper consisted of 250 true/false items (50
      questions of 5 items each) on topics drawn from different disciplines. The
      questions were first constructed and vetted by the individual departments before
      being submitted to a central committee, where the final selection of the MCQs was
      made, based purely on the academic judgement of the committee. RESULTS: There was
      a wide distribution of item difficulty indices in all the MCQ papers analysed.
      Furthermore, the relationship between the difficulty index (P) and discrimination
      index (D) of the MCQ items in a paper was not linear, but more dome-shaped.
      Maximal discrimination (D = 51% to 71%) occurred with moderately easy/difficult
      items (P = 40% to 74%). On average, about 38% of the MCQ items in each paper were
      "very easy" (P > or =75%), while about 9% were "very difficult" (P <25%). About
      two-thirds of these very easy/difficult items had "very poor" or even negative
      discrimination (D < or =20%). CONCLUSIONS: MCQ items that demonstrate good
      discriminating potential tend to be moderately difficult items, and the
      moderately-to-very difficult items are more likely to show negative
      discrimination. There is a need to evaluate the effectiveness of our MCQ items.

PMID- 16565757
TI  - A nationwide survey on the knowledge and attitudes of Malaysian optometry
      students on patients' visual experiences during cataract surgery.
AB  - INTRODUCTION: During cataract surgery under regional (retrobulbar, peribulbar or
      sub- Tenon's) or topical anaesthesia, many patients experience a variety of
      visual sensations in their operated eye intraoperatively. Between 3% and 16.2% of
      patients are frightened by their intraoperative visual experiences, which may
      increase the risk of intraoperative complications and affect patients'
      satisfaction with the surgery. This study aims to determine optometry students'
      beliefs and knowledge of visual sensations experienced by patients during
      cataract surgery under regional and topical anaesthesia. MATERIALS AND METHODS: A
      nationwide survey of all Malaysian optometry students using a standardised, self
      administered questionnaire. RESULTS: All 129 optometry students participated in
      the survey, giving a 100% response rate. Overall, 26.4% and 29.5% of the students
      believed that patients undergoing cataract surgery under regional and topical
      anaesthesia, respectively, may experience no light perception, while 78.3% and
      72.9%, respectively, thought that patients would experience light perception.
      Many respondents also believed that patients might experience a variety of other
      visual sensations. Of all respondents, 70.5% and 74.4% of students believed that
      patients undergoing cataract surgery under regional and topical anaesthesia,
      respectively, may be frightened by their visual experience and 93.0% and 85.3%,
      respectively, felt that preoperative counselling might help to alleviate this
      fear. CONCLUSION: Many optometry students are aware that patients might encounter
      a variety of visual sensations during cataract surgery under local anaesthesia. A
      high proportion of students believe that patients may experience fear as a result
      of the intraoperative visual sensations and felt that preoperative counselling
      would be helpful.

PMID- 16565758
TI  - Angiographic characteristics of acute central serous chorioretinopathy in an
      Asian population.
AB  - INTRODUCTION: Acute central serous chorioretinopathy (CSCR) afflicts young middle
      aged males in the Western population. We aimed to analyse patient demographics
      and to determine the angiographic characteristics of acute CSCR in an Asian
      population. MATERIALS AND METHODS: This is a retrospective study of all patients
      presenting with acute CSCR who had fundal fluorescein angiograms performed within
      a 4-year period (between 1 January 1998 and 31 December 2001). RESULTS: The
      fluorescein angiograms of 128 patients were analysed. The majority were male
      (109/128) with a male-to-female ratio of 5.7:1. The age range of patients was 26
      to 60 years, with a mean age of 41 years. The majority of patients (84%) were
      aged 30 to 50 years. With regard to racial distribution, 83% were Chinese, 6%
      were Malays and 11% were Indians or of other races. Unilateral disease was found
      in 74 patients (58%) and 52 had bilateral disease. The macula was the most common
      site of fluorescein leakage and was found in 97 patients (76%). Almost half the
      patients (44%) had more than one site of disease involvement (i.e., multifocal).
      The inkblot leakage pattern was found in 103 patients (80%). CONCLUSIONS: The
      patient demographics of acute CSCR in our population were compared to that
      reported in the West. The gender ratio was similar, with males being afflicted 6
      to 10 times more compared to females. There was no racial predilection found for
      acute CSCR in the local population. We also found a significant proportion of
      patients with bilateral and multifocal disease compared to the West. The inkblot
      pattern of leakage was the most common pattern seen on angiography. There were a
      significant number of cases with bilateral and multifocal involvement, exceeding
      those reported in non-Asian populations.

PMID- 16565759
TI  - Human limbal progenitor cell characteristics are maintained in tissue culture.
AB  - INTRODUCTION: To determine the differentiation of human limbal epithelial cells
      in tissue culture. MATERIALS AND METHODS: Epithelial cells from the human limbus
      (n = 29) were isolated and cultured in supplemental hormonal epithelial medium
      (SHEM) in the presence of mitomycin C-treated 3T3 feeder layer. Confluent cells
      were airlifted to form multiple layers. The expression of cytokeratin 3 (K3),
      cytokeratin 12 (K12), involucrin, connexin 43 (Cx43), proliferation cell nuclear
      antigen (PCNA) and p63 was studied in normal and airlifted cells by
      immunohistochemistry. Expression levels of K3 and K12 mRNA were examined by real
      time polymerase chain reaction (PCR). RESULTS: The colony-forming efficiency of
      primary cultured (P0) cells was about 19.35 +/- 6.46% (mean +/- SD, n = 7). Real
      time PCR analysis showed that the transcription level of K3 and K12 in cultured
      cells was lower than in freshly isolated limbal cells or cells from central
      cornea (P <0.01). Few cells were positive for K3 in P0 or P1 cells [(1.99 +/-
      1.27)% (n = 7, P0) and (3.96 +/- 1.35)% (n = 4, P1), P = 0.046]. More cells at
      all levels were found to stain positive for PCNA and p63 as compared to K3, K12
      and involucrin. After air-lifting, cell sheets of 3 to 5 epithelial cell layers
      formed. Involucrin showed positive staining in suprabasal layers of the cell
      sheets while connexin 43 was only observed in the basal layer. Staining of K3
      remained sparse. CONCLUSIONS: Human limbal cells isolated from cadaveric tissues
      were able to proliferate in vitro and exhibited a phenotype with characteristics
      similar to that of the limbal stem or progenitor cells.

PMID- 16565761
TI  - Does the advent of endoscopic ultrasound (EUS) sound the death knell for
      endoscopic retrograde cholangiopancreatography (ERCP)?
AB  - INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) has been the
      premier diagnostic and therapeutic endoscopic procedure in the management of
      pancreatic and biliary diseases (PBD). The use of endoscopic ultrasound (EUS),
      including EUS-guided fine needle aspiration (FNA), of pancreatic and biliary
      tumours has become more widely available in the last decade and has gradually
      replaced diagnostic ERCP. Together with EUS, other imaging modalities like
      magnetic resonance cholangiopancreatography (MRCP) have resulted in a decrease in
      the number of ERCPs. With the advent of interventional EUS, ERCP is at risk of
      being completely eclipsed. METHODS: A search of all relevant articles on EUS and
      ERCP from Medline and peer-reviewed journals. RESULTS: This review article
      examines the exact place of ERCP and EUS and their relative contributions in the
      management algorithm of PBD. CONCLUSION: Although diagnostic EUS, including EUS
      guided FNA, is well established in the evaluation of PBD, interventional EUS is
      still in its infancy and its true potential is unknown. Therefore, therapeutic
      ERCP still has a vital, albeit smaller role to play in the treatment of
      pancreatic and biliary diseases.

PMID- 16565760
TI  - Bruch's membrane abnormalities in dome-shaped and mushroom-shaped choroidal
      melanomas.
AB  - INTRODUCTION: Mushroom-shaped choroidal melanoma is known to be associated with
      breaks in Bruch's membrane and is more likely to develop when Bruch's membrane is
      diseased. The study's goal is to determine if diseases causing breaks in Bruch's
      membrane predispose a choroidal melanoma to develop into a mushroom-shaped
      melanoma. MATERIALS AND METHODS: A retrospective review of cases of choroidal
      melanoma seen at our institution was carried out to determine if mushroom-shaped
      melanomas are more common than dome-shaped tumours in patients with macular
      abnormalities involving a loss of Bruch's membrane integrity. Forty-nine eyes of
      48 patients were included in this retrospective study. A dome-shaped or mushroom
      shaped configuration was assigned to each tumour. Macular degeneration, macular
      drusen, retinal pigment epithelial (RPE) stippling, macular oedema, choroidal
      neovascularisation (CNV), angioid streaks, disciform scars, lacquer cracks, and
      myopia greater than -3.00 D, were considered to constitute evidence of potential
      Bruch's membrane breaks and were determined in both eyes. A chi-square evaluation
      was used to compare the proportion of eyes with macular abnormalities in the 2
      tumour configuration groups. RESULTS: The tumour was dome-shaped in 40 eyes (82%)
      and mushroom-shaped in 9 eyes (18%). Macular abnormalities, indicative of loss of
      Bruch's membrane integrity, were seen in 21 (53%) of 40 eyes with dome-shaped
      melanomas and 5 (56%) of 9 eyes with mushroom-shaped melanomas. The proportion of
      eyes with macular abnormalities was not statistically different between the dome
      shaped and mushroom-shaped tumours, as assessed by chi-square analysis (P =
      0.87). CONCLUSIONS: Bruch's membrane disease does not influence the
      differentiation of choroidal melanoma into mushroom-shaped or dome-shaped tumour
      growth patterns.

PMID- 16565762
TI  - The risk of suicidality with selective serotonin reuptake inhibitors.
AB  - Antidepressants are efficacious in the treatment of depression but they are not
      without side effects. The recent findings on the risk of suicide with selective
      serotonin reuptake inhibitor treatment, however, have raised serious concerns
      about the risk-benefit ratio of their use. The development of the concerns is
      traced and the risks discussed, particularly in the child and adolescent group.
      The prescriber needs to be aware of the issues and of the need for close clinical
      monitoring of patients started on selective serotonin reuptake inhibitor
      treatment.

PMID- 16565763
TI  - Septic monoarthritis and osteomyelitis in an elderly man following Klebsiella
      pneumoniae genitourinary infection: case report.
AB  - INTRODUCTION: Klebsiella pneumoniae septic arthritis and osteomyelitis, albeit
      uncommon in adults, are important sites of disseminated infection. Many case
      reports have shown K. pneumoniae as a cause of nosocomial transmitted septic
      arthritis in neonates and children. We report a rare case of an elderly patient
      with K. pneumoniae genitourinary infection spreading to the liver and other extra
      hepatic sites like the prostate and peripheral joint. CLINICAL PICTURE: The
      patient presented with a short history of general malaise, fever and urinary
      symptoms, associated with an acute monoarthritis of the ankle. On admission, he
      was in septic shock. Investigations suggested an infective cause, as evidenced by
      raised total white cell count and pyuria. K. pneumoniae was cultured from both
      urine and ankle synovial fluid. Imaging confirmed multiple liver and prostatic
      abscesses, as well as osteomyelitis of the foot bones adjacent to the ankle.
      TREATMENT: Treatment in this case included surgical drainage of the affected
      joint and surrounding soft tissue structures, in addition to a 6-week course of
      systemic antibiotics. OUTCOME: The patient had good clinical response following
      treatment. In addition, we noted a normalisation of his laboratory parameters and
      resolution of the intraabdominal and pelvic abscesses. CONCLUSION: This case
      emphasises the importance of timely and accurate diagnosis followed by
      appropriate treatment in disseminated K. pneumoniae infection to prevent
      significant morbidity and mortality.

PMID- 16565764
TI  - Postirradiation sarcoma of the sphenoid bone--a case report.
AB  - INTRODUCTION: The development of secondary tumours as a result of radiation
      therapy is a rare but serious complication. CLINICAL PICTURE: This is a case
      report of a 45-year-old Chinese male who developed postirradiation sarcoma of the
      sphenoid bone in less than 5 years after radiation therapy for Stage T3N1M0
      nasopharyngeal carcinoma. DISCUSSION: In the literature, the only case of
      postirradiation osteosarcoma of the sphenoid bone was after radiation therapy for
      craniopharyngioma. There was no previously reported case of postirradiation
      sarcoma of the sphenoid bone after radiation therapy for nasopharyngeal
      carcinoma. CONCLUSION: This is the first case of postirradiation malignant
      fibrous histiocytoma of the sphenoid to be reported. Of about 3000 patients
      treated with radiotherapy for nasopharyngeal carcinoma over a 10-year period in
      Singapore, only 1 patient developed postirradiation tumour of the sphenoid bone.

PMID- 16565765
TI  - Potentially fatal paracetamol overdose and successful treatment with 3 days of
      intravenous N-acetylcysteine regime--a case report.
AB  - INTRODUCTION: Paracetamol overdose is the most common drug overdose worldwide. To
      our knowledge, the maximum number of paracetamol tablets ingested reported in the
      literature is 45 g. CLINICAL PICTURE: We describe a 21-year-old patient who
      acutely ingested 120 tablets, each 500 mg paracetamol (i.e., 60 g equivalent to
      1200 mg/kg body weight) in a suicidal attempt. Our patient also drank 2 bottles
      of codeine-based cough syrup equivalent to 360 mg of codeine. At 6 hours post
      ingestion, her serum paracetamol level was 207 mg/L. The poor prognostic factors
      for paracetamol overdose in our patient included massive paracetamol ingestion
      (confirmed by blood levels), codeine co-ingestion and elevated serum amylase (189
      U/L). TREATMENT: She was treated with a 3-day modified regimen of intravenous N
      acetylcysteine. OUTCOME: The liver function tests and the prothrombin time
      remained normal over the second and third day of admission and the patient was
      discharged without complications on the fifth day. CONCLUSION: From this
      experience we feel that in very severe paracetamol poisoning, a modified regime
      of intravenous N- acetylcysteine for 3 days is safe and efficacious.

PMID- 16565767
TI  - The doctor's multi-instrument tool of the future?

PMID- 16565766
TI  - Intravitreal triamcinolone acetonide for the treatment of diffuse diabetic
      macular oedema--a case report.
AB  - INTRODUCTION: Although laser photocoagulation is the primary treatment for
      diabetic macular oedema, treatment of eyes with diffuse macular oedema has been
      disappointing. Intravitreal injection of steroids is being investigated for the
      treatment of diabetic macular oedema. Preliminary results indicate that steroid
      injections do improve macular oedema, but it is not clear if they improve visual
      acuity. CLINICAL PICTURE, TREATMENT, AND OUTCOME: In this report, we describe a
      patient with a form of diffuse diabetic macular oedema that responded favourably
      to intravitreal steroid injections, with improvements in both foveal thickness
      and visual acuity. CONCLUSION: Intravitreal steroids can be useful for the
      treatment of diffuse diabetic macular oedema.

PMID- 16565768
TI  - Public healthcare--welfare, market share or laissez-faire?--a Sentosa Carlsberg
      skytower view.
AB  - How much the Government should provide for its people in sickness and in health,
      till death do us part, is open to different interpretation in different
      societies. One of the great paradoxes is that welfare states with high taxation
      can be globally competitive, innovative, successful market economies, and still
      provide quality universal healthcare. The Nordic countries, classical welfare
      states, have achieved top global ranking in economic competitiveness. Denmark's
      people are the most satisfied with their healthcare in the world, and the world's
      fourth most responsive healthcare system. This paper examines some of the factors
      that have made Denmark a successful, open and civil society that provides free
      access healthcare to all of its people.

PMID- 16565769
TI  - "The one" annoying patient.

PMID- 16565770
TI  - Interesting in- and outpatient attendances at Hogwarts Infirmary and St Mungo's
      Hospital for magical maladies.
AB  - Ailments afflicting wizarding folk are underreported in the muggle world. The
      recent integration of muggles and magical folk with the return of You-Know-Who
      (aka He Who Must Not Be Named) may result in a similar affliction of inhabitants
      of both worlds. We describe interesting maladies afflicting muggles and wizarding
      folk alike, arising from the use and misuse of magic. We also provide a basic
      glossary of magical ailments, and describe their muggle corollaries. Further
      studies will hopefully result in the development of immunity against the
      unforgivable curses.

PMID- 16565771
TI  - Suicide soon after generalized tonic-clonic seizure. A possible peri-ictal
      phenomenon?
AB  - We report the case of 36-year-old woman who had suffered from focal-unilateral
      right febrile grand mal since she was 9 months old as a result of neonatal
      asphyxia. Over the years, a modification of the clinical picture occurred and
      eventually the patient suffered from paranoid delusions that impaired her ability
      to work. After many years free from seizures, she experienced one day a
      generalized tonic-clonic seizure that required hospitalization and, soon
      thereafter, she committed suicide.

PMID- 16565772
TI  - New perspectives in chondrogenic differentiation of stem cells for cartilage
      repair.

PMID- 16565773
TI  - Prevalence of overweight misperception and weight control behaviors among normal
      weight adolescents in the United States.
AB  - Weight perceptions and weight control behaviors have been documented with
      underweight and overweight adolescents, yet limited information is available on
      normal weight adolescents. This study investigates the prevalence of overweight
      misperceptions and weight control behaviors among normal weight adolescents in
      the U.S. by sociodemographic and geographic characteristics. We examined data
      from the 2003 Youth Risk Behavior Survey (YRBS). A total of 9,714 normal weight
      U.S. high school students were included in this study. Outcome measures included
      self-reported height and weight measurements, overweight misperceptions, and
      weight control behaviors. Weighted prevalence estimates and odds ratios were
      computed. There were 16.2% of normal weight students who perceived themselves as
      overweight. Females (25.3%) were more likely to perceive themselves as overweight
      than males (6.7%) (p < 0.05). Misperceptions of overweight were highest among
      white (18.3%) and Hispanic students (15.2%) and lowest among black students
      (5.8%). Females (16.8%) outnumbered males (6.8%) in practicing at least one
      unhealthy weight control behavior (use of diet pills, laxatives, and fasting) in
      the past 30 days. The percentage of students who practiced at least one weight
      control behavior was similar by ethnicity. There were no significant differences
      in overweight misperception and weight control behaviors by grade level,
      geographic region, or metropolitan status. A significant portion of normal weight
      adolescents misperceive themselves as overweight and are engaging in unhealthy
      weight control behaviors. These data suggest that obesity prevention programs
      should address weight misperceptions and the harmful effects of unhealthy weight
      control methods even among normal weight adolescents.

PMID- 16565774
TI  - Immobilization of zinc phthalocyanines in silicate matrices and investigation of
      their photobactericidal effect on E. coli.
AB  - The aim of the present investigation was to immobilize zinc phthalocyanines in a
      silicate matrix and to test the photobactericidal properties of the matrices so
      prepared toward Esherichia coli in model aqueous media. For the purpose, tetra
      tertiary butyl zinc phthalocyanine (TBZnPc) and zinc phthalocyanine tetrasulfonic
      acid (ZnPcTS) were used. The abilities of these two photosensitizers to generate
      singlet oxygen in solution were compared by following the rate of photobleaching
      of 1,3-diphenylisobenzofuran (DPBF) at 430 nm in dimethylformamide (DMF). The
      results of this study show clearly that, under the conditions used here, the
      TBZnPc is the more effective generator of singlet oxygen; with it the DPBF was
      virtually completely photobleached in 4 min, while with the ZnPcTS under the same
      conditions, it took 12 min to reach this point. Glass conjugates with the two
      phthalocyanines were obtained by the sol-gel technique and were characterized by
      a well-defined color due to the phthalocyanine incorporated in the silicate
      matrix. Glasses with an intense, but inhomogeneous, green color were obtained
      when the tetrasulfonic derivative of the zinc phthalocyanine was used, while blue
      glasses of evenly distributed coloration were formed from the tetra tertiary
      butyl derivative. The ZnPcTS conjugate demonstrates more effective singlet oxygen
      evolution than is the case with the TBZnPc conjugate. These results are the
      opposite of those obtained for the free phthalocyanines in solution. The
      structural formulae of the compounds show that TBZnPc has a more pronounced
      hydrophobic character than the sulfonic derivative. In our view, the relative
      reactivities of the conjugates can be explained by the tetrasulfonic derivative
      being situated mainly in the surface parts of the glass matrix where the
      hydrophilic character is prevailing, while the tertiary butyl derivative is
      mainly present in the internal parts of the matrix as a result of which it is
      less accessible and therefore less active. The results obtained on the effect of
      zinc phthalocyanine conjugates on E. coli show a trend similar to that observed
      with singlet oxygen evolution shown. Thus, for the ZnPcTS conjugate, the log kill
      is 1.32 and for the TBZnPc conjugate, it is 0.98, in each case after 120 min. The
      results obtained show that phthalocyanines can be immobilized successfully in a
      silicate matrix and used for photodisinfection of microbially polluted waters.
      The silicate matrix has some advantages in comparison with other organic
      matrices. It is insoluble in water, resistant towards microorganisms, easy to
      fabricate, and might be developed successfully for the photodisinfection of
      water, e.g., in swimming pools and in other open water reservoirs.

PMID- 16565777
TI  - [Head injury in Buenos Aires city: a prospective, population based, epidemiologic
      study].
AB  - OBJECTIVE: The aim of the study is to present head injury (HI) epidemiology in a
      population of Buenos Aires that represents almost all socioeconomic sectors.
      MATERIAL AND METHOD: Prospective, population based study, approved by the Ethic,
      Education and Research Committees as part of a neurotrauma program. RESULTS: HI
      incidence was 322/100,000 inhabitants, of them mild HI accounted for 93%,
      moderate HI 4% and severe HI 3%. Average age was greater in women than in men (49
      vs. 38 yo, p 0.01). Taking into account population under and over 40 years we
      found several differences: the relative risk (RR) for any kind of HI was 1.97 (CI
      95% 1.77-2.19, p < 0.01, and the RR for motor vehicle (MV) related HI was 2.53
      (CI 95% 2.03-3.17, p < 0.01). Male drivers had a higher RR (16.76 CI 95% 5.35
      52.50, p < 0.01) regardless age. Assaults were also significantly higher in
      people under 40 yo (RR 2.11 IC 95% 1.46-3.03, p < 0.01) increased in young males.
      Self altitude falls were more frequent in population over 40 yo (RR 4.35 CI 95%
      2.61-4.16, p < 0.01) and in women at any age (RR 3.15 CI 95% 2.57-3.87, p <
      0.01). Pedestrian accidents were also more common in population over 40 yo (RR
      1.84 CI 95% 1.41-2.41 p < 0.01). We did not find any other differences concerning
      the remaining trauma mechanisms. CONCLUSIONS: HI incidence in Buenos Aires is
      similar to other printed series, but moderate and severe HI and mortality rates
      are below that ones. Motor vehicle accidents are the leading HI cause, especially
      in the young male population, while self altitude fall and pedestrian accidents
      are prevalent in women and people over 40 yo.

PMID- 16565778
TI  - [Pyogenic brain abscesses: experience with 60 consecutive cases].
AB  - INTRODUCTION: Brain abscess is a focal suppurative process in the brain
      parenchyma that still carries high mortality rates. Outcome is closely related
      with a correct and early management. In order to evaluate this management we have
      reviewed the brain abscesses treated in our Department during the last 14 years.
      MATERIAL AND METHODS: The authors present a retrospective series of 60
      consecutive patients with pyogenic brain abscess treated between January of 1990
      and February of 2004 paying attention to the epidemiology, etiology, clinical
      data, microbiology, treatment modalities and outcome. RESULTS: The male to female
      rate was 5.6 to 1. The average age was 47 years. Hematogenous spread was most
      frequent, followed by contiguous spread. In 22% of the cases, the origin was
      unknown. Regarding the causative pathogens, Gram positive cocci are the most
      frequent (44%), with a 40% incidence of anaerobics. A mixed infection occurred in
      39% of the abscesses. Three modalities of treatment were used: non surgical,
      catheter drainage-aspiration and surgical excision. Outcome was excellent in 52
      patients (86.7%) and 4 patients (6.7%) died. Although outcome was similar in both
      surgical modalities, drainage-aspiration required a second procedure in 20% of
      the cases while this was necessary in only 10% of the patients with abscess
      excision. Length of admission was shorter in the drainage-aspiration group than
      in the excision group (13 and 26 days respectively). Mortality was higher in
      patients with low level of consciousness and age over 70 years. CONCLUSIONS: The
      shorter admission time associated with drainage-aspiration of brain abscesses
      together with its high efficacy and low morbidity suggests that drainage
      aspiration should be used as the first mode of treatment.

PMID- 16565779
TI  - [Neuropsychological impairment in patients with intracranial aneurysms: surgical
      versus endovascular treatment].
AB  - OBJECTIVES: To describe the neuropsychological status of patients with
      intracranial aneurysms and to compare the cognitive status of patients with
      intracranial aneurysm treated by surgical or endovascular methods. MATERIAL AND
      METHODS: Ninety-three cases with intracranial aneurysms treated with surgery (n =
      56) or embolization (n = 37) were included. A neuropsychological assessment was
      applied to both groups retrospectively, at least one year after treatment.
      RESULTS: Neuropsychological impairment was found in both groups. 35.7% of the
      patients treated with surgery and 43.2%, of those treated with embolization did
      not show any cognitive impairment. Visual Memory and Cued Recall of verbal
      information are better in patients treated by embolization. CONCLUSIONS: Our
      results show that a large proportion of patients with intracranial aneurysms have
      cognitive impairment after treatment. Endovascular management may cause less
      impairment in visual and verbal memory. However, bleeding may be the most
      important factor to explain these cognitive impairments.

PMID- 16565780
TI  - Primary central nervous system lymphomas in immunocompetent patients.
AB  - OBJECTIVES: Primary central nervous system lymphoma (PCNSL) is a rare pathology
      and is most often seen in immunodeficient patients. This article presents our
      casuistic of PCNSL in immunocompetent patients and make a literature review on
      this issue with focus on recent advances, investigations, and controversies in
      diagnosis and management of this pathology. MATERIAL AND METHODS: Nine patients
      operated in the last years in our clinics are analysed in relation to sex, age,
      time of symptoms, procedures and adjuvant treatment. Posteriorly the results are
      compared with those in the preview literature. RESULTS: The age ranged from 44-68
      years (middle of 66 years); 62.5% of the patients were female. The mean time of
      symptoms, when the diagnostic was made, was 3.2 months (range 1-6 months). The
      most common symptoms were hemiparesis (present in 75% of the patients) headache
      (37.5%) seizures (25%) and ataxia (25%). The most common localization was the
      parietal, frontal and temporal lobe surface with 25% of the patients for each
      localization. Five patients (50%) were treated with stereotactic biopsy, three
      with surgery (37.5%) and one (12.5%) with both of them. Five patients (62.5%)
      were submitted to pos-operative radiotherapy as adjuvant treatment. In relation
      to the histology, the most common cell type was Diffuse B Cells. CONCLUSIONS:
      This study demonstrated that complete surgical resection followed by radiotherapy
      have shown good results. In opposition to the literature, the authors regard
      chemotherapy as a secondary line treatment and recommend its use only in some
      selected cases.

PMID- 16565781
TI  - Conjoined lumbosacral nerve roots: observations on three cases and review of the
      literature.
AB  - Lumbosacral nerve root anomalies are a rare group of congenital anatomical
      anomalies. Various types of anomalies of the lumbosacral nerve roots have been
      documented in the available international literature. Generally speaking, these
      anomalies may consist of a bifid, conjoined structure, of a transverse course or
      of a characteristic anastomized appearance. Firstly described as an incidental
      finding during autopsies or surgical procedures performed for lumbar disk
      herniations and often asymptomatic, lumbosacral nerve root anomalies have been
      more frequently described in the last years due to the advances made in
      radiological diagnosis (metrizamide myelography and CT, MRI). Our study comprised
      three patients with conjoined lumbosacral nerve roots, representing 0.25% of a
      total of 1200 patients who underwent lumbosacral CT/MRI procedures in the
      Addolorata Hospital and in the Service of Neuroradiology of the University of
      Rome "La Sapienza" during the last three years (March 2001-March 2004). We report
      our experience with three cases of conjoined lumbosacral nerve roots and analyze
      the most important literature on this topic. MR imaging is a better diagnostic
      procedure (in comparison to CT) for the differentiation of nerve root anomalies
      and, in particular, coronal sections furnish a precise definition of the profile
      of the conjoined/enlarged rootlets. In fact, the accurate information derived
      from MRI of multiple planes may be priceless for the preoperative and diagnostic
      evaluation of lumbosacral nerve root anomalies.

PMID- 16565783
TI  - Cavernous malformation of the trigeminal nerve.
AB  - A cavernous malformation involving the Gasserian ganglion, 2nd and 3rd divisions
      of the trigeminal nerve on the left side was resected via an extradural route in
      a 54 year old male. Cavernous malformations of the cranial nerves are rare.
      Specific origin from the trigeminal nerve has not been previously reported.

PMID- 16565782
TI  - Complete surgical resection of high-grade astroblastoma with long time survival:
      case report and review of the literature.
AB  - Astroblastoma is a rare glial neoplasm of unknown origin and uncertain prognosis.
      It usually presents in young adults as a well circumscribed hemispheric mass,
      often associated with a cystic component. The histological features of
      astroblastoma are the presence of typical astroblastic perivascular
      pseudorosettes and perivascular hyalinization. Two different subtypes of
      astroblastoma have been defined based upon histological characteristics.
      Prognosis, however, sometimes is in contradiction with the pathological
      appearance and seems to be more closely related to the grade of surgical
      resection. We present a new case of a patient with a high-grade astroblastoma
      with a long survival time, in whom complete surgical resection was confirmed by
      an early postoperative MRI.

PMID- 16565785
TI  - The Life Engagement Test: assessing purpose in life.
AB  - This article describes a 6-item scale, the Life Engagement Test, designed to
      measure purpose in life, defined in terms of the extent to which a person engages
      in activities that are personally valued. Psychometric data are presented
      including information about the scale's factor structure, internal consistency,
      test-retest reliability, convergent validity, discriminant predictive validity,
      and norms. The data suggest that the Life Engagement Test is psychometrically
      sound across different gender, age, and ethnic groups and is appropriate for
      wider use. Discussion centers on the use of the Life Engagement Test in
      behavioral medicine and health psychology research and recent associations that
      have begun to emerge between the scale and health-relevant outcomes.

PMID- 16565784
TI  - Thermalkalibacillus uzonensis gen. nov. sp. nov, a novel aerobic alkali-tolerant
      thermophilic bacterium isolated from a hot spring in Uzon Caldera, Kamchatka.
AB  - A novel thermophilic, alkali-tolerant, and CO-tolerant strain JW/WZ-YB58(T) was
      isolated from green mat samples obtained from the Zarvarzin II hot spring in the
      Uzon Caldera, Kamchatka (Far East Russia). Cells were Gram-type and Gram stain
      positive, strictly aerobic, 0.7-0.8 mum in width and 5.5-12 mum in length and
      produced terminal spherical spores of 1.2-1.6 mum in diameter with the mother
      cell swelling around 2 mum in diameter (drumstick-type morphology). Cells grew
      optimally at pH(25 degrees C) 8.2-8.4 and temperature 50-52 degrees C and
      tolerated maximally 6% (w/v) NaCl. They were strict heterotrophs and could not
      use either CO or CO(2 )(both with or without H(2)) as sole carbon source, but
      tolerated up to 90% (v/v) CO in the headspace. The isolate grew on various
      complex substrates such as yeast extract, on carbohydrates, and organic acids,
      which included starch, D: -galactose, D: -mannose, glutamate, fumarate and
      acetate. Catalase reaction was negative. The membrane polar lipids were dominated
      by branched saturated fatty acids, which included iso-15:0 (24.5%), anteiso-15:0
      (18.3%), iso-16:0 (9.9%), iso-17:0 (17.5%) and anteiso-17:0 (9.7%) as major
      constituents. The DNA G+C content of the strain is 45 mol%. Phylogenetic analyses
      based on 16S rRNA gene sequences revealed that strain JW/WZ-YB58(T) is distantly
      (<93% similarity) related to members of Bacillaceae. On the basis of 16S rRNA
      gene sequence, physiological and phenotypic characteristics, the isolate JW/WZ
      YB58(T) (ATCC BAA-1258; DSM 17740) is proposed to be the type strain for the type
      species of the new taxa within the family Bacillaceae, Thermalkalibacillus
      uzoniensis gen. nov. sp. nov. The Genbank accession number for the 16S rRNA gene
      sequence is DQ221694.

PMID- 16565786
TI  - A validated system for simulating common carotid arterial flow in vitro:
      alteration of endothelial cell response.
AB  - Pulsations in blood flow alter gene and protein expressions in endothelial cells
      (EC). A computer-controlled system was developed to mimic the common carotid
      artery flow waveform and shear stress levels or to provide steady flow of the
      same mean shear stress in a parallel plate flow chamber. The pseudo-steady state
      shear stress was determined from real-time pressure gradient measurements and
      compared to the Navier-Stokes equation solution. Following 24 h of steady flow
      (SF: 13 dyne/cm2), pulsatile arterial flow (AF: average = 13 dyne/cm2, range = 7
      25 dyne/cm2) or static conditions, heme oxygenase-1 (HO-1) and prostaglandin H
      synthase-2 (PGHS-2) mRNA and protein expressions from human umbilical vein
      endothelial cells were measured. Relative to steady flow, pulsatile arterial flow
      significantly attenuated mRNA upregulation of HO-1 (SF: 7.26 +/- 2.70-fold over
      static, AF: 4.84 +/- 0.37-fold over static; p < 0.01) and PGHS-2 (SF: 6.11+/-1.79
      fold over static, AF: 3.54+/-0.79-fold over static; p < 0.001). Pulsatile
      arterial flow (4.57+/-0.81-fold over static, p < 0.01) also significantly reduced
      the steady-flow-induced HO-1 protein upregulation (7.99 +/- 1.29-fold over
      static). These findings reveal that EC can discriminate between different flow
      patterns of the same average magnitude and respond at the molecular level.

PMID- 16565787
TI  - Different responsiveness to mechanical stress of bone cells from osteoporotic
      versus osteoarthritic donors.
AB  - INTRODUCTION: Osteoporosis (OP) and osteoarthritis (OA) are both common diseases
      in the elderly, but remarkably seldom coexist. The bone defects that are related
      to both diseases develop with increasing age, which suggests that they are
      related to some form of imperfect bone remodeling. Current opinion holds that the
      bone remodeling process is supervised by bone cells that respond to mechanical
      stimuli. An imperfect response of bone cells to mechanical stimuli might thus
      relate to imperfect bone remodeling, which could eventually lead to a lack bone
      mass and strength, such as in OP patients. MATERIALS: To investigate whether the
      cellular response to mechanical stress differs between OP and OA patients, we
      compared the response of bone cells from both groups to fluid shear stress of
      increasing magnitude. Bone cells from 9 female OP donors (age 60-90 year) and 9
      female age-matched OA donors were subjected to pulsating fluid flow (PFF) of low
      (0.4+/-0.1 Pa at 3 Hz), medium (0.6+/-0.3 Pa at 5 Hz), or high shear stress
      (1.2+/-0.4 at 9Hz), or were kept under static culture conditions. RESULTS: We
      found subtle differences in the shear-stress response of the two groups, measured
      as nitric oxide (NO) and prostaglandin E2 (PGE2) production. The NO-response to
      shear stress was higher in the OP than the OA cells, while the PGE2-response was
      higher in the OA cells. CONCLUSIONS: Assuming that NO and PGE2 play a role in
      cell-cell communication during remodeling, these results suggest that slight
      differences in mechanotransduction might relate to the opposite bone defects in
      osteoporosis and osteoarthritis.

PMID- 16565788
TI  - Action of low-level laser therapy on living fatty tissue of rats.
AB  - Little is known about the action of laser rays on normal adipose cells. The
      present study attempts to observe the behavior of fatty cells submitted to laser
      therapy. Dorsal fat pads of normal adult rats were submitted to low-level laser
      irradiation applied locally through intact skin, with four different dose
      schedules (4, 8, 12, and 16 J/cm(2)), with a further group being sham-irradiated.
      Histology, morphometry, immunofluorescence, and electron microscopy were all used
      to analyze irradiated tissues. Changes were restricted to the brown fatty tissue,
      in which a tendency was shown for multivacuolar cells to be transformed into the
      unilocular type. The number of cells which exhibited enlargement and fusion of
      small vacuoles was greater in the 4- and 16-J/cm(2) groups (p<0.05). Increased
      vascular proliferation and congestion was another more evident finding in laser
      treated animals compared to nontreated animals. Low-level laser rays cause brown
      adipose fat droplets to coalesce and fuse. Additionally, they stimulated
      proliferation and congestion of capillaries in the extracellular matrix.

PMID- 16565790
TI  - Gender differences in associations between depressive symptoms and patterns of
      substance use and risky sexual behavior among a nationally representative sample
      of U.S. adolescents.
AB  - OBJECTIVE: This study uses a cluster analysis of adolescents, based on their
      substance use and sexual risk behaviors, to 1) examine associations between risk
      behavior patterns and depressive symptoms, stratified by gender, and 2) examine
      gender differences in risk for depression. METHODS: Data are from a nationally
      representative survey of over 20,000 U.S. adolescents. Logistic regression was
      used to examine the associations between 16 risk behavior patterns and current
      depressive symptoms by gender. RESULTS: Compared to abstention, involvement in
      common adolescent risk behaviors (drinking, smoking, and sexual intercourse) was
      associated with increased odds of depressive symptoms in both sexes. However, sex
      differences in depressive symptoms vary by risk behavior pattern. There were no
      differences in odds for depressive symptoms between abstaining male and female
      adolescents (OR = 1.07, 95% CI 0.70-1.62). There were also few sex differences in
      odds of depressive symptoms within the highest-risk behavior profiles. Among
      adolescents showing light and moderate risk behavior patterns, females
      experienced significantly more depressive symptoms than males. CONCLUSIONS:
      Adolescents who engage in risk behaviors are at increased risk for depressive
      symptoms. Girls engaging in low and moderate substance use and sexual activity
      experience more depressive symptoms than boys with similar behavior. Screening
      for depression is indicated for female adolescents engaging in even experimental
      risk behaviors.

PMID- 16565789
TI  - Lycopene inhibition of IGF-induced cancer cell growth depends on the level of
      cyclin D1.
AB  - BACKGROUND: Insulin-like growth factors (IGFs) play an important role in normal
      and cancerous cell proliferation. Moreover, in recent studies IGF-I has been
      implicated as a major cancer risk factor. The tomato carotenoid lycopene and all
      trans retinoic acid (atRA) have been shown to inhibit growth factor-induced
      proliferation of different types of cancer cells. This action is associated with
      inhibition of cell cycle progression in G0/G1 phase. Cyclin D1 acts as a growth
      factor sensor in G1 phase and is overexpressed in many breast cancer tumors. We
      have previously demonstrated that slowdown of serum-stimulated cell cycle
      progression from G1 to S phase by lycopene correlates with reduction in cyclin D1
      levels, suggesting that the expression of this protein is a main target for
      lycopene's action. AIM OF THE STUDY: To determine whether the reported reduction
      in cyclin D1 level is the key mechanism for lycopene and atRA inhibitory action
      on IGF-I-induced cell cycle progression. RESULTS: Human breast (MCF-7) and
      endometrial (ECC-1) cancer cells were synchronized in G0/G1 phase by serum
      deprivation followed by stimulation with IGF-I. Cell treatment with lycopene and
      atRA inhibited IGF-I-stimulated cell cycle progression from G1 to S phase and
      decreased retinoblastoma protein (pRb) phosphorylation. These events were
      associated with a reduction in cyclin D1 and p21(CIP1/WAF1) level, but not that
      of p27(KIP1). To test the hypothesis that the decrease in cyclin D1 has a major
      role in the inhibitory effects of lycopene and atRA, we examined the ability of
      these two agents to suppress cell cycle progression in MCF-7.7D1.13 cells which
      are capable of expressing cyclin D1 under the control of the Zn-inducible
      metallothionein promoter. Our results showed that ectopic expression of cyclin D1
      can overcome cell cycle inhibition caused by lycopene and atRA. CONCLUSIONS: Our
      findings suggest that attenuation of cyclin Dl levels by lycopene and atRA is an
      important mechanism for the reduction of the mitogenic action of IGF-I.

PMID- 16565791
TI  - Usefulness of grasping a guiding catheter with a loop-snare wire for stent
      placement into the vertebrobasilar artery.
AB  - In cases in which the subclavian artery is severely tortuous or branches with an
      extremely angulated origin, stent placement in the vertebrobasilar artery on the
      approach from the femoral artery is often technically difficult. We report two
      cases in which a stent placement procedure for the vertebrobasilar artery was
      successfully performed by grasping a guiding catheter with a loop-snare wire.
      This technique is useful for tortuous arteries or arteries branching with an
      extremely angulated origin.

PMID- 16565792
TI  - Dual antiplatelet regime versus acetyl-acetic acid for carotid artery stenting.
AB  - Carotid artery stenting has been proposed as an option treatment of carotid
      artery stenosis. The aim of this single-institution study is to compare the dual
      antiplatelet treatment and heparin combined with acetyl-acetic acid, in patients
      who underwent carotid artery stenting. We compared 2 groups of 50 patents each
      who underwent carotid artery stenting for primary atherosclerotic disease. Group
      A received heparin for 24 h combined with 325 mg acetyl-acetic acid and group B
      received 250 mg ticlopidine twice a day combined with 325 mg acetyl-acetic acid.
      Outcome measurements included 30-day bleeding and neurological complications and
      30-day thrombosis/occlusion rates. The neurological complications were 16% in
      group A and 2% in group B (p < 0.05). Bleeding complications occurred in 4% in
      group A and 2% in group B (p > 0.05). The 30-day thrombosis/occlusion rate was 2%
      in group A and 0% in group B (p > 0.05). Dual antiplatelet treatment is
      recommended in all patients undergoing carotid artery stenting.

PMID- 16565794
TI  - "Recovery" vena cava filter: experience in 96 patients.
AB  - The purpose of the study was to assess the clinical safety and efficacy of the
      "Recovery(TM)" (Bard) inferior vena cava (IVC) filter. We retrospectively
      evaluated the clinical and imaging data of patients who had a "Recovery(TM)" IVC
      filter placed between January 2003 and December 2004 in our institution. The
      clinical presentation, indications, and procedure-related complications during
      placement and retrieval were evaluated. Follow-up computed tomography (CT)
      examinations of the abdomen and chest were evaluated for filter-related
      complications and pulmonary embolism (PE), respectively. "Recovery" filters were
      placed in 96 patients (72 males and 24 females; age range: 16-87 years; mean: 46
      years). Twenty-four patients presented with PE, 13 with deep vein thrombosis
      (DVT) and 2 with both PE and DVT. The remaining 57 patients had no symptoms of
      thromboembolism. Indications for filter placement included contraindication to
      anticoagulation (n = 27), complication of anticoagulation (n = 3), failure of
      anticoagulation (n = 5), and prophylaxis (n = 61). The device was successfully
      deployed in the infrarenal (n = 95) or suprarenal (n = 1) IVC through a femoral
      vein approach. Retrieval was attempted in 11 patients after a mean period of 117
      days (range: 24-426). The filter was successfully removed in nine patients (82%).
      Failure of retrieval was due to technical difficulty (n = 1) and the presence of
      thrombus in the filter (n = 1). One of the nine patients who had the filter
      removed developed IVC thrombus after retrieval and another had an intimal tear of
      the IVC. Follow-up abdominal CT (n = 40) at a mean of 80 days (range: 1-513)
      showed penetration of the IVC by the filter arms in 11, of which 3 had fracture
      of filter components. In one patient, a broken arm migrated into the pancreas.
      Asymmetric deployment of the filter legs was seen in 12 patients and thrombus
      within the filter in 2 patients. No filter migration or caval occlusion was
      encountered. Follow-up chest CT (n = 27) at a mean of 63 days (range: 1-386)
      showed PE in one patient (3%). During clinical follow-up, 12 of 96 patients
      developed symptoms of PE and only 1 of the 12 had PE on CT. There was no fatal
      pulmonary embolism in our group of patients following "Recovery" filter
      placement. However, the current version of the filter is associated with
      structure weakness, a high incidence of IVC wall penetration, and asymmetric
      deployment of the filter legs.

PMID- 16565793
TI  - Percutaneous stent-graft repair of a mycotic pulmonary artery pseudoaneurysm.
AB  - Ruptured mycotic pulmonary pseudoaneurysm is a lethal complication. Emergent
      surgical repair is usually recommended, but still associated with a high
      mortality rate. We present a patient in whom mycotic pulmonary pseudoaneurysm was
      a complication after surgical lobectomy 2 weeks earlier. This patient had
      suffered from repeated massive hemoptysis. After emergent surgical repair of the
      ruptured pulmonary artery stump, another episode of massive hemorrhage occurred.
      The pulmonary arteriogram revealed a segmental stenosis and a large, wide-necked,
      lobulated pseudoaneurysm at the left proximal pulmonary artery. We deployed a
      balloon-expandable stent-graft (48 mm in length mounted on a 12 mm x 40 mm
      angioplasty balloon) across the stenotic segment and the neck of the pulmonary
      pseudoaneurysm. Hemostasis was achieved immediately and, under a 4-week
      antibiotic treatment, patient was transferred to a local hospital for medical
      care. This case report demonstrates the benefit of minimally invasive
      endovascular therapy in a critically ill patient. A literature review of the
      etiology and management of mycotic pulmonary pseudoaneurysm is included.

PMID- 16565795
TI  - Acute dissection and contained rupture of a thoracic aortic aneurysm: emergency
      diagnosis with nonenhanced MR angiography.

PMID- 16565796
TI  - Changes in the American interventional radiology literature: comparison over a 10
      year time period.
AB  - PURPOSE: To determine the changes that occurred regarding interventional
      radiologic research in the major American radiology journals between 1992-1993
      and 2002-2003. METHODS: Articles published in three major American radiology
      journals (Journal of Vascular and Interventional Radiology, American Journal of
      Roentgenology, and Radiology) during two distinct 24-month time periods (1992
      1993 and 2002-2003) were evaluated. All articles judged to be pertinent to the
      interventional radiologic community were included. Investigations included in
      journal subheadings other than "interventional" or "vascular radiology" were
      included if the emphasis of the article was on a vascular imaging modality or
      peripheral intervention. Exclusions included: case reports, technical reports,
      letters to the editor, breast interventions, and primary neurointerventions. Data
      were collected regarding the affiliations of the primary author (nationality,
      hospital type, department); primary category of interest of the investigation;
      funding information; and study design variables. Two-by-two chi-squared
      statistical analyses were performed comparing the variables from the early and
      late data sets. RESULTS: A total of 405 articles met the inclusion criteria for
      the early data set (1992-1993); 488 articles met the inclusion criteria for the
      late data set (2002-2003). Variables that demonstrated a statistically
      significant decrease from the early data set to the late data set included:
      articles in which the primary author was from a department of radiology (91.1%
      vs. 86.3%; p < 0.025); articles written by a primary author who was American
      (69.4% vs. 44.6%; p < 0.001); and articles with a primary category of
      investigation that had a nonvascular intervention focus (22.7% vs. 11.9%; p <
      0.001). Variables that demonstrated a statistically significant increase from the
      early data set to the late data set included primary authors from Western Europe
      (18.0% vs. 30.1%; p < 0.001) and Asia (6.6% vs. 18.4%; p < 0.001), the primary
      field of investigation, with significant increases noted for primary cancer
      interventions (6.5% vs. 13.3%; p < 0.001), gynecologic interventions (0.2% vs.
      4.5%; p < 0.001), stent-grafts (0 vs. 2.9%; p < 0.001), and spine interventions
      (0 vs. 1.8%; p < 0.01). Studies receiving funding also demonstrated a significant
      increase when comparing the early and late data sets (11.3% vs. 23.0%,
      respectively; p < 0.001). CONCLUSIONS: Articles published in the American
      radiologic literature have changed significantly over the past 10 years. Primary
      authors are more likely to be nonradiologists and less likely to be American.
      Investigations dealing primarily with nonvascular interventions are less common;
      however, some forms of intervention (particularly cancer interventions) are seen
      more frequently in the literature. The percentage of funded projects has more
      than doubled in the same time frame.

PMID- 16565798
TI  - Left subclavian artery aneurysm rupture in association with aortic coarctation.

PMID- 16565797
TI  - Percutaneous vertebroplasty for osteoporotic compression fracture: multivariate
      study of predictors of new vertebral body fracture.
AB  - PURPOSE: To investigate the risk factors and relative risk of new compression
      fractures following vertebroplasty. METHODS: Initially, we enrolled 104
      consecutive patients with vertebral compression fractures caused by osteoporosis.
      A total of 83 of the 104 patients visited our hospital for follow-up examinations
      for more than 4 weeks after vertebroplasty. Logistic regression analysis of the
      data obtained from these 83 patients was used to determine relative risks of
      recurrent compression fractures, using 13 different factors. RESULTS: We
      identified 59 new fractures in 30 of the 83 patients: 41 new fractures in
      vertebrae adjacent to treated vertebrae; and 18 new fractures in vertebrae not
      adjacent to treated vertebrae. New fractures occurred in vertebrae adjacent to
      treated vertebrae significantly more frequently than in vertebrae not adjacent to
      treated vertebrae. Only cement leakage into the disk was a significant predictor
      of new vertebral body fracture after vertebroplasty (odds ratio = 4.633). None of
      the following covariates were associated with increased risk of new fracture:
      age, gender, bone mineral density, the number of vertebroplasty procedures, the
      number of vertebrae treated per procedure, the cumulative number of vertebrae
      treated, the presence of a single untreated vertebra between treated vertebrae,
      the presence of multiple untreated vertebrae between treated vertebrae, the
      amount of bone cement injected per procedure, the cumulative amount of bone
      cement injected, cement leakage into the soft tissue around the vertebra, and
      cement leakage into the vein.

PMID- 16565799
TI  - Nasolacrimal stenting: toward improving outcomes with a simple modification of
      the song stent.
AB  - The purpose of this study was to evaluate, in a prospective, single-center study,
      the effectiveness of Song's polyurethane stents, modified "in-house," in the
      percutaneous management of epiphora. Patients (n = 170; age range 18-83, mean =
      64; 50 male, 120 female) with severe epiphora had the modified stents inserted
      (183 eyes/195 stents) to treat unilateral/bilateral and complete/partial
      obstruction of the nasolacrimal system. The etiology of the obstruction was
      idiopathic in 119 cases (61%) and chronic dacryocystitis in 76 (39%). The set
      designed by Song was used in all patients but modified by us such that the
      extreme end is cone-shaped. The original technique was slightly modified by us
      and the procedure was conducted on an outpatient basis. The initial technical
      success rate of stent placement was 97%. Resolution of epiphora was complete in
      180 eyes and partial in 3. On follow-up (mean = 18 months; range: 2 days to 24
      months), 165 of 195 stents (85%) remained patent. Primary patency rates at follow
      up were 86%, 84%, 84%, and 79% in the first 6 months, second and third 6 months,
      and the present (24 months), respectively. Stents became obstructed in 30
      patients, but all but 2 were easily withdrawn and 20 of these patients remained
      asymptomatic for a mean of 14 months (secondary patency of 67%). Following stent
      removal, the withdrawn stent was replaced with a new stent in the same
      intervention on 14 occasions. In another six cases, patency was re-established
      without the need of a second stent. The procedure is simple and safe, both in
      stent insertion as well as in mechanical de-blocking and withdrawal when
      occluded. Success was >80 % in the short term (1-year follow-up). Stenting
      failure does not preclude other treatment because with the modification that we
      had introduced, the extreme end of the stent becomes more accessible to
      mechanical de-blocking, withdrawal, and relocation. The levels of primary and
      secondary patencies are promising and warrant more extensive investigation.

PMID- 16565800
TI  - Endofibrosis of iliac arteries in high-performance athletes: diagnostic approach
      and minimally invasive endovascular treatment.
AB  - The aim of this article is to report our experience in the diagnosis of two cases
      of iliac artery endofibrosis or arteriopathy, a rare entity occurring in high
      performance athletes, presenting with intermittent claudication (right-sided in
      both) after maximal exercise. External iliac artery endofibrosis or arteriopathy
      is a likely diagnosis in competitive athletes free of cardiovascular risk factors
      who present with leg claudication. Arteriography and a papaverine-assisted mean
      pressure gradient across the iliac arteries of more than 10 mmHg is a useful
      diagnostic approach. Moreover, balloon angioplasty of the iliac artery in that
      patient, in whom a pressure gradient was detected, resulted in symptomatic relief
      for 2 months followed by mild symptom recurrence. Thus, although balloon
      angioplasty is feasible and safe, it might not be adequate to treat this entity
      and, thus, its value remains undefined.

PMID- 16565801
TI  - Cardiac amyloidosis: typical imaging findings and diffuse myocardial damage
      demonstrated by delayed contrast-enhanced MRI.
AB  - Amyloidosis is a rare systemic disease. However, involvement of the heart is a
      common finding and is the most frequent cause of death in amyloidosis. We report
      the sonographic, scintigraphic, and MRI features of a pathologically proven case
      of cardiac amyloidosis. Delayed contrast-enhanced MR images, using an inversion
      recovery prepped gradient-echo sequence, revealed diffuse enhancement in the wall
      of both left and right ventricles. This enhancement suggested expansion of the
      extracellular space of the myocardium caused by diffuse myocardial necrosis
      secondary to deposition of amyloid.

PMID- 16565803
TI  - Evaluation of the impact of acid mine drainage on the chemistry and the
      macrobenthos in the Carolina stream (San Luis, Argentina).
AB  - The purpose of this study was to evaluate the impact of acid mine drainage on the
      chemistry and the macrobenthos of the Carolina stream (San Luis - Argentina).
      Samples were obtained in the years 1997-1998 at two sites: site C(1), located 200
      m upstream of the drainage, and site C(2), located 800 m downstream. The system
      buffer capacity was evaluated in the non - contaminated site by means of the
      buffer index calculation. The physico - chemical changes observed as a
      consequence of the contribution of acid mine drainage (AMD) were: a decreasing of
      pH and an increase in the ionic concentration, especially sulfate and Fe coming
      from the oxidation produced by chemiolithotrophic bacteria. The values obtained
      indicated a low buffer capacity and a high intrinsic vulnerability of the system
      to resist the impact originated by the AMD, producing a remarkable decreasing of
      pH of the receiving stream. These changes caused modifications in the original
      benthic community that was replaced by organisms more tolerant to the acid
      stress. A reduction in the abundance and in the taxonomic richness of the benthic
      macroinvertebrates was observed when compared with the reference station. An
      increase in the proportion of Chironomidae and of Acari and a decrease in the
      proportion of the remaining taxa were observed. The most sensitive groups were
      Ephemeroptera, Trichoptera and Mollusca. The community was mostly affected by the
      following variables: pH, conductivity, sulfate and dissolved total Fe.

PMID- 16565802
TI  - Antiplasmodial marine natural products in the perspective of current chemotherapy
      and prevention of malaria: a review.
AB  - The difficulty of obtaining an antimalarial vaccine along traditional lines,
      because of the highly adaptive character of the malaria parasite, prompts a
      ceaseless need for new drugs. To this end, marine organisms have been explored
      recently, as reviewed in this article within the perspective of clinically
      available antimalarial drugs and promising candidates. Most promising are
      tetrahydropyrrolo[1,2-alpha]pyrimidinium, bis-indole, and C(11)-N(5) alkaloids
      from sponges; pyridoacridone and decahydroquinoline alkaloids from ascidians; and
      pyrrole alkaloids from fungi, as well as polycyclic polyketides, norditerpene,
      and polyketide endoperoxides, terpene isonitriles, and, particularly, mixed
      biogenesis alpha-galactosyl ceramides from sponges. The first and the latter
      classes of agents best fulfill the requirements for combinatorial synthesis in
      providing a wide variety of compounds for high-throughput screening and toxicity
      tests. These results came largely from nonprofit organizations, a trend that we
      foresee will continue. However, partnership with the pharmaceutical industry was
      and is needed to bring candidate drugs to the clinic. In any event, success will
      not be achieved without political plans to make the results of technology easily
      available to poor populations.

PMID- 16565804
TI  - The effects of small dam removal on the distribution of sedimentary contaminants.
AB  - With increasing concern over degradation of aquatic resources, issues of
      liability, and maintenance costs, removal of small dams has become increasing
      popular. Although the benefits of removal seem to outweigh the drawbacks, there
      is a relative paucity of studies documenting the extent and magnitude of
      biological and chemical changes associated with dam removal, especially those
      evaluating potential changes in contaminant inventories. In August and November
      of 2000, a run-of-the-river dam on Manatawny Creek (southeast Pennsylvania) was
      removed in a two-stage process. To assess the effects of dam removal on the
      contaminant redistribution within the creek, sedimentary concentrations of
      polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and
      trace metals (Cd, Cr, Cu, Ni, Pb, Zn) were evaluated prior to and several months
      after removal. Pre- and post-removal analyses revealed elevated and spatially
      variable concentrations of total PAHs (ranging from approximately 200 to 81,000
      ng(g dry weight) and low to moderate concentrations of trace metals and PCBs. The
      concentrations of these sedimentary contaminants pre- versus post-removal were
      not significantly different. Additionally, though the impoundment received storm
      water run-off and associated contaminants from the adjacent city of Pottstown,
      the total inventory of fine-grain sediments in the impoundment prior to removal
      was very low. The removal of the low-level Manatawny Creek dam did not
      significantly redistribute contaminants downstream. However, each dam removal
      should be assessed on a case by case basis where the potential of sedimentary
      contaminant redistribution upon dam removal exists.

PMID- 16565805
TI  - Airborne dust particle counting techniques.
AB  - The paper briefly describes an electro-optical system for counting of dust
      particles, which is based on the scattering phenomena. Utilizing the scattering
      of light by various size particles present in the environment, various particle
      counting techniques have been developed in order to measure the scattered
      intensity of light. Light scatters in all directions but much more in the so
      called near forward direction 17( composite function) off axis, at 163( composite
      function) from the light source in the visible range. On the basis of two
      techniques, the right angle and forward angle scattering, opto-mechanical systems
      have been developed which measure scattered intensity and particulate matter. The
      forward scattering Nephelometer is more sensitive and therefore is more suitable
      for pollution monitoring than the right angle scattering Nephelometer. Whereas
      the right angle scattering Nephelometer has the utility in extremely low
      concentration in ppb level owing to the excellent light trap efficiency in
      comparison to forward scattering Nephelometer. In this paper measurement
      techniques and measurement results associated with design and development of a
      real time particle analyser are also discussed.

PMID- 16565806
TI  - Environmental monitoring of land-use and land-cover changes in a Mediterranean
      region of Turkey.
AB  - Unprecedented rates of human-induced changes in land use and land cover (LULC) at
      local and regional scales lead to alterations of global biogeochemical cycles.
      Driving forces behind LULC changes mainly include rapid growth rates of
      population and consumption, lack of valuation of ecological services, poverty,
      ignorance of biophysical limitations, and use of ecologically incompatible
      technologies. One of the major ecological tragedies of the commons in a
      Mediterranean region of Turkey is the loss of Lake Amik at the expense of
      increasing the area of croplands, which used to provide vital ecosystem goods and
      services for the region. In this study, we aimed at quantifying the effects of
      past land-use transitions on soil organic carbon (SOC) pools (0-20 cm) in a
      Mediterranean region of 3930 km(2), between 1972 and 2000. LULC changes were
      quantified from a time series of satellite images of Landsat-MSS in 1972, Landsat
      5 TM in 1987, and Landsat-7 ETM+ in 2000 using geographic information systems.
      The study showed that the increase in croplands between 1972 and 1987 took place
      at the expense of the irreversible losses of Lake Amik and its related wetlands
      of over 53 km(2). In the period of 1972 to 2000, croplands, settlements, and
      evergreen forests increased by 174%, 106%, and 14%, respectively. The increase in
      settlements occurred mostly to the detriment of croplands. Given the average
      rates of all the land-use transitions, and associated changes in SOC density for
      the study region of 3930 km(2), total SOC pool was estimated to decrease by 14.1%
      from 130.1 Mt in 1972 to 111.7 Mt in 2000.

PMID- 16565807
TI  - Bioaccumulation of trace elements in a wild grass three years after the
      Aznalcollar mine spill (South Spain).
AB  - In this paper, we surveyed the concentration of nine trace elements (As, Cd, Cu,
      Fe, Mn, Ni, Pb, Tl and Zn) in bermudagrass (Cynodon dactylon) 3 years after the
      mine spill in Aznalcollar (south Spain). The results were compared with those
      that had been obtained for the same species in a previous study, 18 months after
      the accident. Three types of soil condition were determined: i) unaffected soils
      (UN, control); ii) cleaned up and amended soils (A, amended); and (iii) non
      amended soils, inaccessible to the clean-up and remediation operations (NA, non
      amended). The trace element concentrations in the plants were lower than those
      reported in the first sampling for both washed (plant tissues) and unwashed
      plants (as consumed by herbivores). Apart from Cd, trace elements concentrations
      (plant tissues) were similar in the A and the UN soils. In the NA soils, the Cd,
      Fe, Mn, Zn and Pb levels in unwashed plants were excessive for animal
      consumption. This wild grass seems to be suitable as a soil stabilizer for spill
      affected soils and as a biomonitor for soil pollution by some trace elements (As,
      Cu and Zn); however, its potential for phytoextraction is negligible.

PMID- 16565808
TI  - Using NDVI to assess vegetative land cover change in central Puget Sound.
AB  - We used the Normalized Difference Vegetation Index (NDVI) in the rapidly growing
      Puget Sound region over three 5-year time blocks between 1986-1999 at three
      spatial scales in 42 Watershed Administrative Units (WAUs) to assess changes in
      the amounts and patterns of green vegetation. On average, approximately 20% of
      the area in each WAU experienced significant NDVI change over each 5-year time
      block. Cumulative NDVI change over 15 years (summing change over each 5-year time
      block) was an average of approximately 60% of each WAU, but was as high as 100%
      in some. At the regional scale, seasonal weather patterns and green-up from
      logging were the primary drivers of observed increases in NDVI values. At the WAU
      scale, anthropogenic factors were important drivers of both positive and negative
      NDVI change. For example, population density was highly correlated with negative
      NDVI change over 15 years (r = 0.66, P < 0.01), as was road density (r = 0.71, P
      < 0.01). At the smallest scale (within 3 case study WAUs) land use differences
      such as preserving versus harvesting forest lands drove vegetation change. We
      conclude that large areas within most watersheds are continually and heavily
      impacted by the high levels of human use and development over short time periods.
      Our results indicate that varying patterns and processes can be detected at
      multiple scales using changes in NDVIa values.

PMID- 16565809
TI  - Response of 1,2-dichloroethane-adapted microbial communities to ex-situ
      biostimulation of polluted groundwater.
AB  - The microbial community of a groundwater system contaminated by 1,2
      dichloroethane (1,2-DCA), a toxic and persistent chlorinated hydrocarbon, has
      been investigated for its response to biostimulation finalized to 1,2-DCA removal
      by reductive dehalogenation. The microbial population profile of samples from
      different wells in the aquifer and from microcosms enriched in the laboratory
      with different organic electron donors was analyzed by ARISA (Amplified Ribosomal
      Intergenic Spacer Analysis) and DGGE (Denaturing Gradient Gel Electrophoresis) of
      16S rRNA genes. 1,2-DCA was completely removed with release of ethene from most
      of the microcosms supplemented with lactate, acetate plus formate, while cheese
      whey supported 1,2-DCA dehalogenation only after a lag period. Microbial species
      richness deduced from ARISA profiles of the microbial community before and after
      electron donor amendments indicated that the response of the community to
      biostimulation was heterogeneous and depended on the well from which groundwater
      was sampled. Sequencing of 16S rRNA genes separated by DGGE indicated the
      presence of bacteria previously associated with soils and groundwater polluted by
      halogenated hydrocarbons or present in consortia active in the removal of these
      compounds. A PCR assay specific for Desulfitobacterium sp. showed the enrichment
      of this genus in some of the microcosms. The dehalogenation potential of the
      microbial community was confirmed by the amplification of dehalogenase-related
      sequences from the most active microcosms. Cloning and sequencing of PCR products
      indicated the presence in the metagenome of the bacterial community of a new
      dehalogenase potentially involved in 1,2-DCA reductive dechlorination.

PMID- 16565811
TI  - Allocentric cues do not always improve whole body reaching performance.
AB  - The aim of this investigation was to gain further insight into control strategies
      used for whole body reaching tasks. Subjects were requested to step and reach to
      remembered target locations in normal room lighting (LIGHT) and complete darkness
      (DARK) with their gaze directed toward or eccentric to the remembered target
      location. Targets were located centrally at three different heights. Eccentric
      anchors for gaze direction were located at target height and initial target
      distance, either 30 degrees to the right or 20 degrees to the left of target
      location. Control trials, where targets remained in place, and remembered target
      trials were randomly presented. We recorded movements of the hand, eye and head,
      while subjects stepped and reached to real or remembered target locations.
      Lateral, vertical and anterior-posterior (AP) hand errors and eye location, and
      gaze direction deviations were determined relative to control trials. Final hand
      location errors varied by target height, lighting condition and gaze
      eccentricity. Lower reaches in the DARK compared to the LIGHT condition were
      common, and when matched with a tendency to reach above the low target, help
      explain more accurate reaches for this target in darkness. Anchoring the gaze
      eccentrically reduced hand errors in the AP direction and increased errors in the
      lateral direction. These results could be explained by deviations in eye
      locations and gaze directions, which were deemed significant predictors of final
      reach errors, accounting for a 17-47% of final hand error variance. Results also
      confirmed a link between gaze deviations and hand and head displacements,
      suggesting that gaze direction is used as a common input for movement of the hand
      and body. Additional links between constant and variable eye deviations and hand
      errors were common for the AP direction but not for lateral or vertical
      directions. When combined with data regarding hand error predictions, we found
      that subjects' alterations in body movement in the AP direction were associated
      with AP adjustments in their reach, but final hand position adjustments were
      associated with gaze direction alterations for movements in the vertical and
      horizontal directions. These results support the hypothesis that gaze direction
      provides a control signal for hand and body movement and that this control signal
      is used for movement direction and not amplitude.

PMID- 16565810
TI  - Effect of speed manipulation on the control of aperture closure during reach-to
      grasp movements.
AB  - This study investigates coordination between hand transport and grasp movement
      components by examining a hypothesis that the hand location, relative to the
      object, in which aperture closure is initiated remains relatively constant under
      a wide range of transport speed. Subjects made reach-to-grasp movements to a
      dowel under four speed conditions: slow, comfortable, fast but comfortable, and
      maximum (i.e., as fast as possible). The distance traveled by the wrist after
      aperture reached its maximum (aperture closure distance) increased with an
      increase of transport speed across the speed conditions. This finding rejected
      the hypothesis and suggests that the speed of hand transport is taken into
      account in aperture closure initiation. Within each speed condition, however, the
      closure distance exhibited relatively small variability across trials, even
      though the total distance traveled by the wrist during the entire transport
      movement varied from trial to trial. The observed stability in aperture closure
      distance across trials implies that the hand distance to the object plays an
      important role in the control law governing the initiation of aperture closure.
      Further analysis showed that the aperture closure distance depended on the
      amplitude of peak aperture as well as hand velocity and acceleration. To clarify
      the form of the above control law, we analyzed four different mathematical
      models, in which a decision to initiate grasp closure is made as soon as a
      specific movement parameter (wrist distance to target or transport time) crosses
      a threshold that is either a constant value or a function of the above-mentioned
      other movement-related parameters. Statistical analysis performed across all
      movement conditions revealed that the control law model (according to which grasp
      initiation is made when hand distance to target becomes less than a certain
      linear function of aperture amplitude, hand velocity, and hand acceleration)
      produced significantly smaller residual errors than the other three models. The
      findings support the notion that transport-grasp coordination and grasp
      initiation is based predominantly on spatial characteristics of the arm movement,
      rather than movement timing.

PMID- 16565812
TI  - Do you know where your arm is if you think your head has moved?
AB  - Reproduction of a previously presented elbow position is affected by changes in
      head position. As movement of the head is associated with local biomechanical
      changes, the aim of the present study was to determine if illusory changes in
      head position could induce similar effects on the reproduction of elbow position.
      Galvanic vestibular stimulation (GVS) was applied to healthy subjects in supine
      lying. The stimulus was applied during the presentation of an elbow position,
      which the subject then reproduced without stimulation. In the first study, 13
      subjects received 1.5 mA stimuli, which caused postural sway in standing,
      confirming that the firing of vestibular afferents was affected, but no illusory
      changes in head position were reported. In the second study, 13 subjects received
      2.0-3.0 mA GVS. Six out of 13 subjects reported consistent illusory changes in
      head position, away from the side of the anode. In these subjects, anode right
      stimulation induced illusory left lateral flexion and elbow joint position error
      towards extension (p=0.03), while anode left tended to have the opposite effect
      (p=0.16). The GVS had no effect on error in subjects who did not experience
      illusory head movement with either 1.5 mA stimulus (p=0.8) or 2.0-3.0 mA stimulus
      (p=0.7). This study demonstrates that the accuracy of elbow repositioning is
      affected by illusory changes in head position. These results support the
      hypothesis that the perceived position of proximal body segments is used in the
      planning and performance of accurate upper limb movements.

PMID- 16565813
TI  - Genotype and subtype analyses of Cryptosporidium isolates from dairy calves and
      humans in Ontario.
AB  - To assess the importance of dairy cattle as a source of human Cryptosporidium
      infections in Ontario, Canada, 44 Cryptosporidium isolates from neonatal dairy
      calves and 11 from sporadic human cases of cryptosporidiosis in the province were
      genotyped by PCR-RFLP analyses of the Cryptosporidium oocyst wall protein (COWP)
      and 18S rRNA genes. Isolates were also subtyped by sequence analysis of the 60
      kDa glycoprotein (GP60) gene. All bovine isolates successfully subtyped belonged
      to Cryptosporidium parvum subtype family (allele) IIa. Seven subtypes of this
      family were identified among the bovine isolates. Four human isolates were
      Cryptosporidium hominis, of alleles Ia, Id, and Ie. Of the remaining seven human
      specimens, four were C. parvum allele IIa, two were C. parvum of an undetermined
      subtype, and one was identified as Cryptosporidium cervine genotype. Three of the
      C. parvum isolates from humans were the same subtypes as isolates from the
      calves. These findings suggest that cattle and other ruminants may be a source of
      sporadic human infections in Ontario. This is the first published description of
      Cryptosporidium genotypes and subtypes in Ontario, and is the second published
      report of human infection with Cryptosporidium cervine genotype.

PMID- 16565814
TI  - A preliminary survey of gastrointestinal and haemoparasites of beef cattle in the
      tropical livestock farming system in Nan Province, northern Thailand.
AB  - Parasitism is a primary cause of production losses in most cattle-producing
      countries of the world, including Thailand. A cross-sectional study was designed
      to determine baseline data on the prevalence of gastrointestinal and
      haemoparasites of beef cattle in Nan Province, northern Thailand and to
      investigate the factors associated with the prevalence of parasitic infections. A
      total of 207 faecal and 162 blood samples were collected during the summer of
      2005. The basic data of management were recorded, including the number of animals
      on the farm or in the village, major animal health problems, deworming programme
      and veterinary service. The overall prevalence of gastrointestinal parasitic
      infections was 61% (126/207). The most common helminth infections in this study
      were rumen flukes 28% (58), followed by strongyles 27% (55), and the rest were
      due to Strongyloides 1% (2) and Trichuris 1% (2). The common protozoan infections
      were Buxtonella cysts 2% (5) and coccidia oocysts 2% (4). Of the 162 blood
      samples examined, 50% (81) contained Theileria sp., 2% (4) trypanosome, and 1%
      (1) microfilariae. The high rate of parasitic infections in these areas might be
      related to the poor management by the farmers, such as sharing the same grazing
      pasture.

PMID- 16565816
TI  - Subgenotype analysis of Cryptosporidium parvum isolates from humans and animals
      in Japan using the 60-kDa glycoprotein gene sequences.
AB  - Cryptosporidium parvum is a well-known intestinal parasite which is associated
      with severe acute diarrhea in humans and animals. This parasite is composed of
      morphologically identical but genetically different multiple genotypes. In
      humans, cryptosporidiosis is mainly caused by two C. parvum genotypes, human
      genotype (previously known as genotype 1 and recently proposed as new species C.
      hominis) and cattle genotype (previously known as genotype 2). However, recent
      molecular studies indicate the genetic heterogeneity among the isolates of C.
      parvum human or cattle genotype. Therefore, identification of the isolates at the
      subgenotype level is more useful for control of the Cryptosporidium infection or
      for understanding of the population structure of C. parvum genotypes. In the
      present study, we identified the subgenotypes of the C. parvum human or cattle
      genotype isolates from humans and animals in Japan using DNA sequencing analysis
      of the C. parvum 60-kDa glycoprotein gene (GP60) and showed the new subgenotype
      in a raccoon dog isolate. This study suggested that C. parvum cattle genotype
      might be composed of zoonotic and host-specific multiple subgenotypes.

PMID- 16565815
TI  - Quick and efficient purification of Giardia intestinalis cysts from fecal
      samples.
AB  - Giardia intestinalis is an intestinal parasite that has sparked considerable
      interest because of the public health problem it creates and because it is
      regarded as one of the earliest divergent eukaryotes. The present report
      describes a new method for quick, clean, and effective isolation of G.
      intestinalis cysts from fecal samples. The isolated cysts have the quality
      required for biochemical studies of the excystation process.

PMID- 16565817
TI  - Dynamics of Diplostomum spathaceum infection in snail hosts at a fish farm.
AB  - Ecologically sustainable disease prevention in intensive monocultures, such as
      fish farming, is based on the knowledge of the ecology of parasites and the
      identification of the key proportion of host populations for parasite life
      cycles. In this paper, we examined the life cycle dynamics of the pathogenic
      trematode Diplostomum spathaceum at a fish farm during a period of 1 year,
      focusing especially on the pattern of infection in the snail host (Lymnaea
      stagnalis) population, which is the key phase in the parasite life cycle
      regarding preventative actions. We found that (1) the infection varied seasonally
      in snails, being highest in late August; (2) the prevalence of infection and the
      proportion of individuals releasing cercariae were strongly dependent on snail
      size; (3) the parasite over-wintered in snails as dormant sporocysts and 4) the
      mortality of infected snails was not likely to differ from uninfected individuals
      during winter. Furthermore, the seasonality and development of the infection in
      the snails corresponded to the pattern of infection observed in the tracer
      rainbow trout caged in the farm area. This pattern of infection also indicated
      strong spatiality of the infection, probably because of differences in the size
      of the snail population between the ponds rather than differences in the
      prevalence of infection. Overall, present results indicate a possibility for late
      summer outbreaks of D. spathaceum, but also that snail prevention at farms could
      be conducted more efficiently by considering both size-dependent infection and
      the timing of cercarial release.

PMID- 16565818
TI  - Effects of L-type Ca2+ channel antagonists on in vitro excystment of Paragonimus
      ohirai metacercariae induced by sodium cholate.
AB  - The inhibitory effects of L-type Ca2+ channel antagonists on Na cholate-induced
      in vitro excystment (CIIE) of Paragonimus ohirai metacercariae were studied. At
      concentrations of 10 microM, nicardipine and nimodipine inhibited CIIE completely
      and by approximately 92%, respectively. Nitrendipine and (+/-)-verapamil
      inhibited CIIE by about one half and one third, respectively. Nifedipine and
      diltiazem did not inhibit CIIE significantly. At higher concentrations,
      nitrendipine at 20 microM completely inhibited CIIE, and (+/-)-verapamil at 40
      microM inhibited CIIE by 93%. Nifedipine and diltiazem inhibited CIIE only
      slightly and little, respectively, even at 40 microM. Complete inhibition by
      nicardipine at 10 microM required preincubation of metacercariae with the
      antagonist for 15 min. The inhibitory effects of nicardipine and nimodipine were
      reversible, and most of the nimodipine-treated metacercariae could excyst within
      1 h after being washed, but the nicardipine-treated ones started to excyst 1 h
      after washing. Nicardipine suppressed the active movement of encysted juveniles
      evoked by Na cholate, whereas nimodipine did not suppress this significantly.
      These results suggested that L-type Ca2+ channels appeared to be involved in CIIE
      of P. ohirai metacercariae and that the inhibitory effect of the channels was due
      primarily to factors other than the inhibition of muscular activity, probably
      involving the secretion and release of enzymes lytic against the metacercarial
      cyst wall.

PMID- 16565819
TI  - Symptom patterns and relative distribution of functional bowel disorders in 1,023
      gastroenterology patients in Iran.
AB  - BACKGROUND AND AIMS: There are scanty data on functional bowel disorder (FBD)
      patterns in Iran. This first-time study tried to provide preliminary data on
      relative distribution of different types of FBD and their symptom patterns in
      Iranian patients. METHODS: A consecutive sample of 1,023 patients in an
      outpatient gastroenterology clinic in central Tehran was interviewed using two
      questionnaires based on Rome II criteria from December 2004 to May 2005 to detect
      FBD patients. RESULTS: Of 1,023 gastroenterology patients, 410 met Rome II
      criteria for FBD; functional constipation, 115 (28%); irritable bowel syndrome
      (IBS), 110 (27%) [IBS-C, 29%; IBS-D, 11%; IBS-A, 60%]; functional bloating, 102
      (25%); unspecified FBD, 76 (18%); and functional diarrhea, 7 (2%). FBD had no
      association with age or level of education, while it was more frequent in women
      (P=0.001). FBD was also more frequent among those with a history of
      abdominal/pelvic surgery (P=0.021). IBS patients had a lower mean of age compared
      with non-FBD group, while patients with constipation were older (Mann-Whitney U
      test, P=0.006). Constipation-related symptoms were the most frequent symptoms
      among IBS patients. Constipation (<3 defecations/week) was also the most frequent
      change in bowel habit in bloating and unspecified FBD patients. Fourteen percent
      of IBS consulters and 8.7% of functional constipation consulters met Rome II
      criteria for dyspepsia (disregarding the ruling out of upper gastrointestinal
      organic disease). Only 20% of patients with functional constipation were
      consulters. CONCLUSIONS: Population-based studies at provincial levels are
      essential to clarify FBD patterns in each provincial district in the country.

PMID- 16565820
TI  - A large preclinical animal model to assess ex vivo skin gene therapy
      applications.
AB  - Because of its easy accessibility, the skin is a very attractive target for gene
      therapy purposes. To study potential clinical applications in a preclinical
      setting, appropriate animal models are needed. Pig skin is very similar to human
      skin, and a variety of human diseases that are potentially amenable to gene
      therapy applications also occur in pigs. Only a few studies have analyzed the
      engraftment of transduced keratinocytes (KC) in pigs, however, with limited
      success. We describe a porcine model in which pig KC were transduced ex vivo with
      a retroviral vector encoding a marker gene and subsequently grafted onto the
      autologous host, utilizing a relatively simple grafting technique. Enhanced
      transduction efficiency was achieved by an optimized transduction protocol
      including centrifugation of the retroviral vector at a temperature of 32 degrees
      C. Transduced KC were then seeded onto acellular dermis, forming a stratified
      epidermis. Grafting was performed by creating full thickness wounds and placing
      the skin graft onto the muscle fascia, covered by a protective skin flap for
      several days. Successful engraftment of transduced KC was demonstrated by
      immunohistochemistry of biopsies taken at different time points, showing
      transgene expression in 40-50% of grafted KC. After 4 weeks, KC expressing a
      foreign marker gene was lost, suggesting a transgene-specific immune response in
      the immunocompetent pigs and highlighting the potential problems for clinical
      gene therapy studies when transferring new genetic material into a patient. The
      model presented here may be used to examine applications of skin gene therapy,
      where retroviral vectors encoding endogenous pig genes will be expressed in the
      skin.

PMID- 16565822
TI  - Symptom clusters: establishing the link between clinical practice and symptom
      management research.

PMID- 16565821
TI  - Anti-inflammatory agents in the management of alimentary mucositis.
AB  - BACKGROUND: Alimentary mucositis is a significant complication of cancer therapy,
      with important clinical and economic implications. MATERIALS AND METHODS: In June
      2005, the Mucositis Study Group of the Multinational Association of Supportive
      Care in Cancer/International Society for Oral Oncology conducted an evidence
      based review of the literature on alimentary mucositis. The goal of this
      literature review was to update previously published guidelines for the
      management of mucositis. RESULTS: This article reports the findings of the
      subgroup charged with reviewing the literature related to anti-inflammatory
      interventions. Considerable preclinical and clinical evidence suggests that the
      use of anti-inflammatory agents may be a promising approach to reduce the
      severity of mucositis. However, there was not enough evidence to support any new
      guidelines advocating the use of any specific anti-inflammatory intervention.
      CONCLUSION: Thus, there is a need for well-designed clinical trials evaluating
      the use of anti-inflammatory agents in the management of mucositis.

PMID- 16565823
TI  - [Implants in the hand].
AB  - Increasingly, implants in the region of hand joints and the wrist represent an
      alternative for the treatment of post-traumatic, inflamed, or degenerative joint
      damage. The diversity of hand functions also results in varied solutions, which
      are effective in their stability, mobility, and distraction. Different materials
      are necessary for this, and they require subtile radiological control. The native
      X-ray represents the substantial method to observe migration of the implants.
      Each interface between titanium, ceramic, zirconium, pyrocarbon, and silicon to
      the bone has to be assessed differently in order to obtain a relevant statement.
      The finger joints and to a limited extent the wrist represent the artificial
      joints with limited alternative therapy. Other implants in the hand should only
      be applied after strict indication and patient compliance, as arthrodesis and
      resection arthroplasty have shown very good long-term results.

PMID- 16565825
TI  - Salmonella serovar Give: an unusual pathogen causing splenic abscess.

PMID- 16565824
TI  - [Chronic mesenteric ischemia with consecutive ischemic colitis. Suggestions for
      diagnosis and therapy].
AB  - The incidence of acute mesenteric ischaemia has decreased over the last few
      years. However, cases of chronic mesenteric ischaemia have grown in number, as
      this disease is the most frequent disorder of the large intestine in the elderly.
      The typical clinical presentation of ischaemic colitis develops gradually and
      only becomes recognisable in the late stage of the disease. We present a 51-year
      old woman with a history of unexplained abdominal pain. Multislice CT
      demonstrated an irregular stenosis of the truncus coeliacus and superior
      mesenteric artery. A Riolan's anastomosis was present and showed excellent
      perfusion. After a hemicolectomy 6 years previously, different radiologic
      procedures and endoscopy revealed a structural tumour at the colon transversum we
      suspected to be malignant. A sequential procedure was conducted. In a first
      vascular intervention, the truncus coeliacus was reconstructed with a vein patch,
      and the mesenteric superior artery was replanted. The second laparotomy was
      performed for revision of the superior mesenteric artery and resection of the
      intestinal tumour. However, no carcinoma was found in histological examination.
      In fact, the individual multidisciplinary considerations play an important role
      in determining the best treatment strategy, if intervention is warranted. Based
      on our experience, sequential intervention with a common clinical pathway is the
      safest and most suitable and economic procedure for curing complex pathologies.

PMID- 16565826
TI  - Nationwide spread of clonally related CTX-M-15-producing multidrug-resistant
      Klebsiella pneumoniae strains in Hungary.

PMID- 16565827
TI  - Differential effects of nicotine on alcohol consumption in men and women.
AB  - RATIONALE: Nicotine and alcohol are frequently co-used, suggesting that use of
      one drug may facilitate use of the other. Furthermore, because men and women
      differ in their responses to both drugs, it is possible that men and women also
      differ in their responses to the combination of nicotine and alcohol. OBJECTIVE:
      This experiment was designed to investigate the effects of nicotine on
      consumption and subjective and physiological effects of alcohol in healthy male
      and female social drinkers. MATERIALS AND METHODS: Healthy light smoking, social
      drinkers (22 men and 12 women) participated in a three-session, double-blind
      within-subject study. They were pretreated with transdermal nicotine (7 or 14 mg)
      or placebo, followed two h later by an alcoholic beverage, and subsequent
      opportunities to "purchase" and consume more of the same drink. Outcome measures
      included the number of alcoholic beverages consumed and subjective and
      physiological effects. RESULTS: Nicotine increased alcohol consumption in men,
      whereas it decreased alcohol consumption in women. These effects were even more
      pronounced after excluding participants reporting nausea after nicotine
      administration. Nicotine alone increased subjective arousal in men but decreased
      positive mood in women. Nicotine increased the sedative-like effects of alcohol
      in both sexes. CONCLUSIONS: These findings indicate that both the subjective
      effects of nicotine and the effects of nicotine on alcohol consumption differ
      markedly in men and women. The findings extend existing data on sex differences
      in the effects of either nicotine or cigarette smoking on alcohol consumption,
      and support the idea that the pharmacological effects of nicotine may differ in
      men and women.

PMID- 16565828
TI  - Endoglin (CD105) is a target for an oral DNA vaccine against breast cancer.
AB  - Endoglin (CD105), a co-receptor in the TGF-beta receptor complex, is over
      expressed on proliferating endothelial cells in the breast tumor neovasculature
      and thus offers an attractive target for anti-angiogenic therapy. Here we report
      the anti-angiogenic/anti-tumor effects achieved in a prophylactic setting with an
      oral DNA vaccine encoding murine endoglin, carried by double attenuated
      Salmonella typhimurium (dam-, AroA-) to a secondary lymphoid organ, i.e., Peyer's
      patches . We demonstrate that an endoglin vaccine elicited activation of antigen
      presenting dendritic cells, coupled with immune responses mediated by CD8+ T
      cells against endoglin-positive target cells. Moreover, we observed suppression
      of angiogenesis only in mice administered with the endoglin vaccine as compared
      to controls. These data suggest that a CD8+ T cell-mediated immune response
      induced by this vaccine effectively suppressed dissemination of pulmonary
      metastases of D2F2 breast carcinoma cells presumably by eliminating proliferating
      endothelial cells in the tumor vasculature. It is anticipated that vaccine
      strategies such as this may contribute to future therapies for breast cancer.

PMID- 16565829
TI  - Chronic haematogenous Pseudomonas aeruginosa osteomyelitis of the clavicle, a
      case report and review of the literature.

PMID- 16565830
TI  - Ultrasonography after the first febrile urinary tract infection in children.
AB  - The importance of ultrasonography after the first febrile urinary tract infection
      has been recently challenged. The aim of this study was to evaluate the role of
      ultrasonography in detection of significant non-reflux abnormalities in the
      kidneys and the urinary tract, and to determine whether these findings influence
      treatment in these children. The clinical data and ultrasonography results of 155
      children admitted to a university hospital with the first febrile urinary tract
      infection were analysed retrospectively. Renal ultrasonography was abnormal in 23
      patients (14.8%). The major portion of these patients (81%) were younger than 2
      years of age. Management of nine of these patients was changed based primarily on
      ultrasonography findings. Four of these patients were treated operatively.
      CONCLUSION: Our findings indicate that ultrasonography performed after the first
      urinary tract infection may offer clinically important information about non
      reflux abnormalities in the kidneys and urinary tract that can affect the
      management of children with these complications.

PMID- 16565831
TI  - Molecular and hematological profiles of hemoglobin EE disease with different
      forms of alpha-thalassemia.
AB  - We describe hematologic and DNA characterization of hemoglobin (Hb) E homozygote
      with various forms of alpha-thalassemia in Thai individuals. Altogether, 131
      unrelated adult subjects with Hb EE at routine Hb analysis were studied. Forty
      two cases were found to carry alpha-thalassemia with ten different genotypes.
      These included 21 cases with alpha(+)-thalassemia heterozygote (
      alpha(3.7)/alphaalpha), one case with alpha(+)-thalassemia heterozygote (
      alpha(4.2)/alphaalpha), six cases with Hb Constant Spring heterozygote
      (alpha(CS)alpha/alphaalpha), four cases with homozygous alpha(+)-thalassemia (
      alpha(3.7)/-alpha(3.7)), one case with homozygous alpha(+)-thalassemia (
      alpha(4.2)/-alpha(4.2)), two cases with compound alpha(+)-thalassemia/Hb Constant
      Spring (-alpha(3.7)/alpha(CS)alpha), one case with compound alpha(+)
      thalassemia/Hb Pakse (-alpha(3.7)/alpha(PS)alpha), four cases with alpha(0)
      thalassemia heterozygote (--(SEA)/alphaalpha), and, unexpectedly, two cases with
      compound alpha(0)-thalassemia/alpha(+)-thalassemia [(--(SEA)/-alpha(3.7)) and (-
      (SEA)/-alpha(4.2))]. The hematological expression of these Hb E homozygotes with
      various forms of alpha-thalassemia was presented comparatively with those of the
      89 cases of pure Hb E homozygotes. Overlapping levels of Hb E, Hb F, and other
      hematological parameters were observed which did not predict clinical severity,
      indicating a need for alpha-globin gene analysis for accurate diagnosis and
      improved genetic counseling.

PMID- 16565832
TI  - Phase I/II trial of biweekly docetaxel and cisplatin with concurrent thoracic
      radiation for stage III non-small-cell lung cancer.
AB  - OBJECTIVES: We conducted phase I and II studies of biweekly docetaxel and
      cisplatin with concurrent radiotherapy, followed by consolidation chemotherapy
      with the same drugs in patients with locally advanced, unresectable non-small
      cell lung cancer (NSCLC). Our objectives were to define the maximum-tolerated
      dose and dose-limiting toxicity (DLT) in the phase I study, and to determine the
      response rate, toxicity, and survival rate at the recommended dose (RD) in the
      phase II study. METHODS: Patients with unresectable stage IIIA and IIIB NSCLC
      were studied. Six to eight cycles of docetaxel and cisplatin were administered at
      2-week intervals. In the phase I study, patients received four dose levels: level
      1, docetaxel/cisplatin=30/40 mg/m2; level 2, 35/40; level 3, 40/40; and level 4,
      45/40. Radiotherapy was delivered at a rate of 2 Gy per fraction/day up to a
      total dose of 60 Gy over the course of 6 weeks, during the first three cycles of
      chemotherapy. RESULTS: DLT comprised neutropenia at level 4 in the phase I study
      (n=15), and level 3 was considered the RD. In the phase II study (n=46), two
      patients had a complete response (4.3%) and 34 had a partial response (73.9%),
      for an overall response rate of 78.2% [95% CI (66.3-90.2%)]. The survival rate
      was 69.1% at 1 year and 39.6% at 2 years, with a median survival time of 19.1
      months. Leukopenia, neutropenia, anemia, and radiation esophagitis were the most
      common toxic reactions, with Grade > or = 3 reactions occurring at rates of 77,
      70, 17, and 8%, respectively. CONCLUSION: Biweekly docetaxel and cisplatin with
      concurrent RT was active and well tolerated in patients with unresectable stage
      III NSCLC.

PMID- 16565833
TI  - The influence of the time interval between monoHER and doxorubicin administration
      on the protection against doxorubicin-induced cardiotoxicity in mice.
AB  - PURPOSE: Despite its well-known cardiotoxicity, the anthracyclin doxorubicin
      (DOX) continues to be an effective and widely used chemotherapeutic agent. DOX
      induced cardiac damage presumably results from the formation of free radicals by
      DOX. Reactive oxygen species particularly affect the cardiac myocytes because
      these cells seem to have a relatively poor antioxidant defense system. The
      semisynthetic flavonoid monohydroxyethylrutoside (monoHER) showed
      cardioprotection against DOX-induced cardiotoxicity through its radical
      scavenging and iron chelating properties. Because of the relatively short final
      half-life of monoHER (about 30 min), it is expected that the time interval
      between monoHER and DOX might be of influence on the cardioprotective effect of
      monoHER. Therefore, the aim of the present study was to investigate this possible
      effect. METHODS: Six groups of 6 BALB/c mice were treated with saline, DOX alone
      or DOX (4 mg/kg i.v.) preceded by monoHER (500 mg/kg i.p.) with an interval of
      10, 30, 60 or 120 min. After a 6-week treatment period and additional observation
      for 2 weeks, the mice were sacrificed. Their cardiac tissues were processed for
      light microscopy, after which cardiomyocyte damage was evaluated according to
      Billingham (in Cancer Treat Rep 62(6):865-872, 1978). Microscopic evaluation
      revealed that treatment with DOX alone induced significant cardiac damage in
      comparison to the saline control group (P<0.001). RESULTS: The number of damaged
      cardiomyocytes was 9.6-fold (95% CI 4.4-21.0) higher in mice treated with DOX
      alone than that in animals of the control group. The ratio of aberrant
      cardiomyocytes in mice treated with DOX preceded by monoHER and those in mice
      treated with saline ranged from 1.6 to 2.8 (mean 2.2, 95% CI 1.2-4.1, P=0.019).
      The mean protective effect by adding monoHER before DOX led to a significant 4.4
      fold reduction (P<0.001, 95% CI 2.3-8.2) of abnormal cardiomyocytes. This
      protective effect did not depend on the time interval between monoHER and DOX
      administration (P=0.345). CONCLUSION: The results indicate that in an outpatient
      clinical setting monoHER may be administered shortly before DOX.

PMID- 16565834
TI  - Progressive massive osteolysis secondary to benign squamous epithelial
      colonisation in chronic osteomyelitis.
AB  - Although the rare complication of squamous cell carcinoma in chronic
      osteomyelitis is well known, benign squamous epithelial proliferation can also
      occur, causing osteolysis and fracture. The radiological and correlated
      pathological features of osteolysis from this benign complication of chronic
      osteomyelitis are presented.

PMID- 16565835
TI  - Posterior longitudinal ligament status in cervical spine bilateral facet
      dislocations.
AB  - OBJECTIVE: It is generally accepted that cervical spine bilateral facet
      dislocation results in complete disruption of the posterior longitudinal
      ligament. The goal of this study was to evaluate the integrity of numerous spine
      stabilizing structures by MRI, and to determine if any associations between
      injury patterns exist with respect to the posterior longitudinal ligament status.
      DESIGN: Retrospective case series. PATIENTS: A retrospective review was performed
      of 30 cervical spine injury subjects with bilateral facet dislocation. Assessment
      of 1.5T MRI images was carried out for: intervertebral disc disruption, facet
      fracture, and ligamentous disruption. Statistical analyses were performed to
      evaluate for associations between various injury patterns and posterior
      longitudinal ligament status. RESULTS: The frequency of MRI abnormalities was:
      anterior longitudinal ligament disruption (26.7%), disc herniation or disruption
      (90%), posterior longitudinal ligament disruption (40%), facet fracture (63.3%)
      and disruption of the posterior column ligament complex (97%). There were no
      significant associations between injury to the posterior longitudinal ligament
      and other structures. Compared to surgical reports, MRI was accurate for
      determining the status for 24 of 26 ligaments (three of three anterior
      longitudinal ligament, seven of nine posterior longitudinal ligament, and 14 of
      14 posterior column ligament complex) but generated false negatives in two
      instances (in both MRI showed an intact posterior longitudinal ligament that was
      torn at surgery). CONCLUSIONS: In contradistinction to the existing concept, the
      posterior longitudinal ligament can remain intact in a substantial proportion of
      hyperflexion injuries that produce bilateral cervical facet dislocation.
      Posterior longitudinal ligament integrity is not associated with any other injury
      pattern related to the anterior longitudinal ligament, intervertebral disc or
      facet fracture.

PMID- 16565836
TI  - Diffuse-type giant cell tumor of the subcutaneous thigh.
AB  - Diffuse-type giant cell tumor is an extra-articular form of pigmented
      villonodular synovitis. The localized form of this lesion (tenosynovial giant
      cell tumor) is frequent, representing the most common subset arising from the
      synovium of a joint, bursa or tendon sheath, with 85% of cases occurring in the
      fingers. The less frequent diffuse-type giant cell tumors are commonly located in
      the periarticular soft tissues, but on rare occasions these lesions can be purely
      intramuscular or subcutaneous We report the case of a 26-year-old female with
      diffuse-type giant cell tumor of the subcutaneous thigh, remote from a joint,
      bursa or tendon sheath. A review of the literature did not reveal any similar
      description of a diffuse-type giant cell tumor completely within the subcutaneous
      thigh, remote from a joint, bursa or tendon sheath. These lesions were initially
      regarded as inflammatory or reactive processes, but since the identification of
      clonal abnormalities in these patients, and in view of their capacity for
      autonomous growth, they are now widely considered to represent benign neoplasms.

PMID- 16565837
TI  - Demineralized bone matrix and hydroxyapatite/tri-calcium phosphate mixture for
      bone healing in rats.
AB  - PURPOSE: Hydroxyapatite/tri-calcium phosphate (HA/TCP) mixture is an
      osteoconductive material used as a bone graft substitute, and demineralised bone
      matrix (DBM) is an osteoinductive material. A combination of DBM and HA/TCP
      mixture would probably create a composite with both osteoconductive and
      osteoinductive properties. The purpose of this study was to determine the effect
      of the combination of DBM and HA/TCP mixture on healing of rat radius segmental
      defects. METHODS: Twenty-four adult male Wistar rats were used. Bilateral radial
      defects were created in each animal. Radial defects were implanted with DBM,
      HA/TCP mixture and a combination of both substances. Control defects were left
      unfilled. Ten weeks after implantation, the animals were sacrificed, and the
      radii were evaluated by radiograhic and histopathological studies. RESULTS: The
      use of DBM alone demonstrated improved healing on radiographic and histological
      studies compared to other groups and the control group. There were no differences
      between the other two groups and the control group. CONCLUSION: The DBM group
      showed the best healing response. Combined use of DBM and HA/TCP mixture did not
      improve bone healing, and the osteoinductive properties of DBM were inhibited by
      HA/TCP mixture.

PMID- 16565838
TI  - Serum interleukin-6 response to elective total hip replacement surgery.
AB  - The focus of this work was to study the serum interleukin-6 (IL-6) response to
      total hip replacement. Twenty-one patients received an uncemented total hip
      prosthesis. Venous samples for IL-6 determination were drawn before and after
      surgery. The IL-6 response was significant, and a peculiar heterogeneity of
      response was apparent: the medians of peak levels (82.3 pg/ml) and of areas under
      the response curve (51.8 pg/ml) distinguished between IL-6 high responders (HR)
      and IL-6 low responders (LR; p<0.0001). No difference was found in the gender
      composition of these groups, whereas the HR patients were older than the LR
      patients (p<0.05). The amount of IL-6 increase was found to correlate with
      patient age, whereas its slope was found to correlate with the duration of the
      surgical procedure. Moreover, the HR group presented a higher degree of
      hyperthermia in the days after surgery compared with the LR patients, without
      evidence of differences in postoperative complications, time to mobilisation, or
      length of stay in hospital. The main finding of our study was the evidence of a
      remarkable variability between individuals in the IL-6 response to surgery.
      Future studies are needed to identify the factors involved in the regulation of
      the cytokine response to surgery.

PMID- 16565839
TI  - Spacer prostheses in two-stage revision of infected knee arthroplasty.
AB  - At present, no consensus exists on the best spacer alternative for the management
      of two-stage exchange arthroplasty of infected knee arthroplasties. In this
      retrospective study, patient records of 24 patients, who had undergone two-stage
      revisions in which resterilised prosthetic components were used as spacers, were
      reviewed. The outcome was compared to that of operations performed during the
      same period (1993-2003) using cement spacers (n=10). With an average follow-up of
      32 months, control of infection was achieved in 26 cases (76%), with good or
      excellent clinical outcome in 19 cases (56%). Treatment failed and resulted in
      amputation at the level of the thigh before reimplantation in one case. Three
      patients did not undergo reimplantation. In four cases (12%) infection relapsed.
      The reinfection rate did not differ between the two spacer groups. Patients
      treated with resterilised components had a superior range of motion during the
      period between the two stages. Operative time was shorter and there was less
      blood loss in the reimplantation arthroplasty when a prosthetic spacer was used.
      We consider resterilised prosthetic components a safe and effective alternative
      to cement spacers in the management of infected knee arthroplasties.

PMID- 16565840
TI  - Custom mega-prosthetic replacement for proximal humeral tumours.
AB  - We used custom mega-prostheses in 57 patients with aggressive benign and
      malignant tumours of the proximal humerus. The most common tumour was
      osteosarcoma, followed by giant cell tumour and chondrosarcoma. We achieved extra
      articular and wide resection margins in all primary malignant tumours and narrow
      margins in benign and metastatic tumours. Six patients died of disease, 4
      patients developed local recurrences and 43 were continuously disease free at an
      average follow-up of 5.5 years (range 2-14.5 years). Five patients required
      revision replacements. The most common complications were proximal subluxation
      and aseptic loosening. Functional outcome was satisfactory in 78% of cases.

PMID- 16565841
TI  - Possible selection effects for radiation risk estimates in Japanese A-bomb
      survivors: reanalysis of acute radiation symptoms data.
AB  - An earlier analysis examined the possibility of bias in the Life Span Study (LSS)
      cohort by studying Japanese A-bomb survivors with bomb-related acute injuries and
      those without such injuries. The authors reported significantly higher radiation
      risks, both for cancers and non-cancers, among those survivors with acute
      injuries compared with those without. The risks were reported to be particularly
      large among survivors aged <10 or > or =55 years of age at the time of bombings.
      The aim of this paper is to examine these findings more closely using the LSS
      acute effects data. All the analyses were carried out using Poisson regression.
      Relative risk models were fitted with adjustment for sex and other factors.
      Significant differences in relative risk between survivors with epilation and
      burns and those without epilation and burns are found for leukaemia. There is
      also some evidence for heterogeneity in the leukaemia risk between survivors with
      two or more acute injuries and those with no injuries, but the evidence is
      disappeared when survivors with one or more injuries are compared with those
      without injuries. For solid cancers, cardiovascular disease and all deaths
      combined, the risks do not differ to a statistically significant extent between
      survivors with and without injuries. There is no statistically significant
      heterogeneity in risk across age-at-exposure categories for survivors with
      injuries. For all deaths combined, relative risk estimates and their
      uncertainties are significantly higher for survivors exposed at ages <10 years
      when compared with other exposure ages, but risks are not significantly raised
      for survivors exposed at > or =55 years of age. With the exception of leukaemia,
      the findings from the present work are inconsistent with those of Stewart and
      Kneale.

PMID- 16565842
TI  - Chromosome aberration analysis and the influence of mitotic delay after simulated
      partial-body exposure with high doses of sparsely and densely ionising radiation.
AB  - The influence of high doses of sparsely and densely ionising radiation on the
      yield of aberrant human peripheral lymphocytes in simulated partial-body
      exposures was studied by investigating radiation-induced chromosome aberration
      frequencies, namely dicentric and centric ring chromosomes. Peripheral blood
      samples from two volunteers were irradiated with high doses of 200 kV X-rays or
      neutrons with a mean energy of <E (n)> or =2.1 MeV and partial-body exposure was
      simulated by mixing irradiated and non-irradiated blood from the same two donors
      in proportions of 25, 50, and 75%. Lymphocytes were cultured and first-division
      metaphase cells were collected after culture times of 48, 56, and 72 h. A
      significant underrepresentation of dicentric and centric ring chromosomes was
      observed at the three highest doses of X-rays between the different culture times
      for nearly all proportions. After neutron irradiation, some significant
      differences were observed at all doses and all culture times, without however,
      revealing any systematic pattern. The distribution of dicentric and ring
      chromosomes showed overdispersion for both radiation types. After simulated
      partial-body exposures with 200 kV X-rays and <E (n)> or =2.1 MeV neutrons,
      strong mitotic delays could be observed, which depended on both the irradiated
      volume and the applied dose: the smaller the irradiated volume and the higher the
      dose, the higher was the selective advantage of non-irradiated cells. For the
      purpose of biological dosimetry after partial body exposure, an extension of the
      lymphocyte culture time is suggested at least for doses > or =3.0 Gy of 200 kV X
      rays and > or =0.5 Gy of <E (n)> or =2.1 MeV neutrons in order to prevent a
      systematic underestimation of cytogenetic damage.

PMID- 16565843
TI  - cDNA cloning of nine S alleles and establishment of a PCR-RFLP system for
      genotyping European pear cultivars.
AB  - Nine full-length cDNAs of S ribonucleases (S-RNases) were cloned from stylar RNA
      of European pear cultivars by RT-PCR and 3' and 5' RACE. Comparison of the
      nucleotide sequences between the nine S-RNases cloned and 13 putative S alleles
      previously amplified by genomic PCRs revealed that seven corresponded to Sa, Sb,
      Sd, Se, Sh, Sk and Sl alleles, and the other two were new S alleles (designated
      as Sq and Sr alleles). Genomic PCR with a set of a8FTQQYQa9 and a8EP-anti
      IIWPNVa9 primers was used to amplify nine S alleles; 1,414 bp (Sl), ca. 1.3 kb
      (Sk and Sq), 998 bp (Se), 440 bp (Sb) and ca. 350 bp (Sa, Sd, Sh and Sr). Among
      these, S alleles of similar size were discriminated by digestion with BaeI,
      BglII, BssHII, HindIII, EcoO109I and SphI. The PCR amplification of S allele
      following digestion with the restriction enzymes provided a PCR-RFLP system for
      rapid S-genotyping European pear cultivars harboring nine S alleles. The PCR-RFLP
      system assigned a total of 63 European pear cultivars to 25 genotypes. Among
      these, 14 genotypes were shared by two or more cultivars, which were cross
      incompatible. These results suggested that the genes cloned represented the S
      RNases from European pear, and that there were many cross-incompatible
      combinations among European pear varieties.

PMID- 16565844
TI  - A first linkage map of globe artichoke (Cynara cardunculus var. scolymus L.)
      based on AFLP, S-SAP, M-AFLP and microsatellite markers.
AB  - We present the first genetic maps of globe artichoke (Cynara cardunculus var.
      scolymus L. 2n=2x=34), constructed with a two-way pseudo-testcross strategy. A F1
      mapping population of 94 individuals was generated between a late-maturing, non
      spiny type and an early-maturing spiny type. The 30 AFLP, 13 M-AFLP and 9 S-SAP
      primer combinations chosen identified, respectively, 352, 38 and 41 polymorphic
      markers. Of 32 microsatellite primer pairs tested, 12 identified heterozygous
      loci in one or other parent, and 7 were fully informative as they segregated in
      both parents. The female parent map comprised 204 loci, spread over 18 linkage
      groups and spanned 1330.5 cM with a mean marker density of 6.5 cM. The equivalent
      figures for the male parent map were 180 loci, 17 linkage groups, 1239.4 and 6.9
      cM. About 3% of the AFLP and AFLP-derived markers displayed segregation
      distortion with a P value below 0.01, and were not used for map construction. All
      the SSR loci were included in the linkage analysis, although one locus did show
      some segregation distortion. The presence of 78 markers in common to both maps
      allowed the alignment of 16 linkage groups. The maps generated provide a firm
      basis for the mapping of agriculturally relevant traits, which will then open the
      way for the application of a marker-assisted selection breeding strategy in this
      species.

PMID- 16565845
TI  - The role of FDG-PET/CT in the detection of recurrent colorectal cancer.
AB  - PURPOSE: The conventional diagnostic techniques used to assess recurrence of
      colorectal cancer (CRCR) often yield unspecific findings. Integrated FDG-PET/CT
      seems to offer promise for the differential diagnosis of benign and malignant
      lesions. The aim of this study was to compare the value of FDG-PET and PET/CT in
      the detection of CRCR subsequent to colonic resection or rectal amputation.
      METHODS: The population for this retrospective study comprised 84 patients with
      suspected CRCR. The sensitivity, specificity and accuracy of PET and PET/CT were
      calculated for (a) intra-abdominal extrahepatic recurrences, (b) extra-abdominal
      and/or hepatic recurrences and (c) all recurrences, and tumour marker levels were
      analysed. RESULTS: The sensitivity, specificity and overall accuracy of PET in
      detecting intra-abdominal extrahepatic CRCR were 82%, 88% and 86%, respectively,
      compared with 88%, 94% and 92%, respectively, for PET/CT. The corresponding
      figures for detection of extra-abdominal and/or hepatic CRCR were 74%, 88% and
      85% for PET and 95%, 100% and 99% for PET/CT. Considering the entire population,
      the sensitivity, specificity and overall accuracy of PET were 80%, 69% and 75%,
      respectively, compared with 89%, 92% and 90%, respectively, for PET/CT. FDG
      PET/CT examination correctly detected 40 out of a total of 45 patients with CRCR.
      Two of five patients with falsely negative FDG-PET/CT findings had local
      microscopic recurrences and one had miliary liver metastases. Of 39 patients
      without CRCR, three showed false positive FDG-PET/CT results. Two of these cases
      were due to increased accumulation in inflammatory foci in the bowel wall, while
      one was due to haemorrhaging into the adrenal gland. CONCLUSION: FDG-PET/CT
      appears to be a very promising method for distinguishing a viable tumour from
      fibrous changes, thereby avoiding unnecessary laparotomy.

PMID- 16565846
TI  - Loss of neuronal integrity: a cause of hypometabolism in patients with traumatic
      brain injury without MRI abnormality in the chronic stage.
AB  - PURPOSE: Traumatic brain injury (TBI) causes brain dysfunction in many patients.
      However, some patients have severe brain dysfunction but display no abnormalities
      on magnetic resonance imaging (MRI). There have been some reports of
      hypometabolism even in such patients. The purpose of this study was to
      investigate the relationship between metabolic abnormality and loss of neuronal
      integrity in TBI patients with some symptoms but without MRI abnormalities.
      METHODS: The study population comprised ten patients with TBI and ten normal
      volunteers. All of the patients were examined at least 1 year after the injury. (
      15)O-labelled gas PET and [(11)C]flumazenil (FMZ) positron emission tomography
      (PET) were carried out. The cerebral metabolic rate of oxygen (CMRO(2)) and
      binding potential (BP) images of FMZ were calculated. Axial T2WI, T2*WI and FLAIR
      images were obtained. Coronal images were added in some cases. RESULTS: All of
      the patients had normal MRI findings, and all showed areas with abnormally low
      CMRO(2). Low uptake on BP images was observed in six patients (60%). No lesions
      that showed low uptake on BP images were without low CMRO(2). On the other hand,
      there were 14 lesions with low CMRO(2) but without BP abnormalities. CONCLUSION:
      These results indicate that there are metabolic abnormalities in TBI patients
      with some symptoms after brain injury but without abnormalities on MRI. Some of
      the hypometabolic lesions showed low BP, indicating a loss of neuronal integrity.
      Thus, FMZ PET may have potential to distinguish hypometabolism caused by neuronal
      loss from that caused by other factors.

PMID- 16565847
TI  - Comparison of 18F-FDG-PET and standard procedures for the pretreatment staging of
      children and adolescents with Hodgkin's disease.
AB  - PURPOSE: The aim of this study was to perform a prospective, blinded comparison
      of( 18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and
      conventional staging methods (CSMs) for initial staging of children and
      adolescents with Hodgkin's disease (HD). METHODS: Over a period of 4 years, 55
      children and adolescents with HD (mean age 15.5 years, range 3.9-18.9 years) were
      prospectively recruited into the study. They underwent 61 FDG-PET studies using a
      dedicated whole-body PET scanner as a part of their initial staging work-up. PET
      findings were correlated with the results of CSMs, including computed tomography
      (CT), ultrasound, bone scanning and bone marrow examination. Discordant findings
      were resolved by magnetic resonance imaging or clinical follow-up (range 2-47
      months). RESULTS: PET correctly changed the staging in 15% of patients (seven
      upstagings, two downstagings). Only two out of 61 patients (3%) were not
      accurately staged by PET; in these children, PET missed small lymphoma nodules
      detected on lung CT. The sensitivity of PET and CSMs for pretreatment staging was
      96.5% and 87.5%, respectively; specificity was 100% and 60%, and accuracy, 96.7%
      and 85.2%, respectively. Upon combination of FDG-PET and lung CT, the diagnostic
      accuracy reached 100% in our series. CONCLUSION: Our study showed that whole-body
      FDG-PET is an efficient and useful method for the initial staging of children
      with HD. FDG-PET in combination with lung CT should be recommended as a screening
      method prior to other conventional imaging modalities to plan a rational staging
      protocol. Large multicentre prospective studies are necessary to verify this
      conclusion.

PMID- 16565849
TI  - EMG and duration of ventilatory support in children with Guillain-Barre syndrome.
AB  - RATIONALE: Predicting length of stay in the intensive care unit (ICU) in children
      with Guillain-Barre syndrome may help decision-making at admission. MATERIALS AND
      METHODS: Between 1996 and 2003, we attended to 30 children with Guillain-Barre
      syndrome who required ventilatory support in ICU. We prospectively collected
      different variables that could potentially predict prolonged length of stay and
      ventilatory support in ICU. CONCLUSION: Using Cox proportional hazard analysis we
      found that lack of electrical excitability was the best predictor.

PMID- 16565848
TI  - To: Holstein A, Stumvoll M (2005) Contraindications can damage your health--is
      metformin a case in point? Diabetologia 48:2454-2459.

PMID- 16565850
TI  - Familial occurrence of moyamoya disease: a clinical study.
AB  - BACKGROUND: We reviewed a consecutive series of moyamoya disease (MMD) in
      children and studied their familial pedigrees to determine whether they showed
      specific clinical features or patterns of inheritance, and to investigate any
      correlation between familial MMD and common Asian diseases. METHODS: Cases of
      familial MMD (N=10) were reviewed in the aspect of clinical presentation, such
      as, symptoms and signs, age of onset, imaging studies including magnetic
      resonance imaging (MRI), cerebral angiography, and single photon emission
      computed tomography (SPECT), and operative results including complications, to
      identify differences between these patients and those with sporadic MMD (N=194).
      The male to female ratio in those with familial MMD was 4:6 and mean age was 8
      years (3-17). All were ischemic cases and five showed cerebral infarction on MRI.
      As a preliminary genetic study, familial pedigrees were examined. In addition,
      their familial histories concerning common Asian diseases, such as, hepatic
      disease, cancers, stroke, coronary heart disease, amyloidosis, and systemic lupus
      erythematosus, were investigated by telephone survey. RESULTS AND CONCLUSIONS:
      The familial MMD cases did not reveal any differences from the other MMD children
      in terms of clinical findings, imaging data, or surgical results. In our series,
      five cases (50%) showed MMD between siblings. Familial MMD relations were also
      observed with cousins, a mother, and an aunt. No specific pattern of genetic
      inheritance was observed, and no relation was found between the familial
      occurrence of MMD and common Asian diseases.

PMID- 16565851
TI  - Role of temozolomide in pediatric brain tumors.
AB  - FEATURES OF TEMOZOLOMIDE: Temozolomide (TMZ) belongs to the imidazotetrazine
      class and it is a DNA-methylating agent that has a good antitumor activity.
      Despite of dacarbazine, TMZ is spontaneously converted into its active metabolite
      5-(3-methyltriazen-l-yl)imidazole-4-carboxamide at physiologic pH, so it is not
      required in enzymatic demethylation in the liver. TMZ is able to cross the blood
      brain barrier and is stable at gastric acid pH so it has almost 100% oral
      bioavailability and is rapidly absorbed after it is taken orally. TEMOZOLOMIDE IN
      CANCER PATIENTS: On the basis of the relatively safe toxicity and the findings
      achieved in adult malignant gliomas, phase I and II clinical trials were set up
      to evaluate the opportunity of using this novel drug in pediatric cancer, too. In
      this review, we evaluate the antitumor activity of TMZ against high-grade
      gliomas, low-grade-gliomas, and medulloblastoma/primitive neuroectodermal tumors
      analyzing several phases I and II clinical trials in children. CONCLUSIONS: In
      spite of the poor activity of TMZ against pediatric brain tumors, the use of the
      drug in combination with other compounds should be evaluated in phases I and II
      clinical trials. Moreover, the evaluation of the methylation status of the O6
      methylguanine DNA methyltransferase promoter in glioblastoma biopsy specimens
      could be assayed as a predictive factor of TMZ efficacy.

PMID- 16565852
TI  - Lymphocytic hypophysitis with central diabetes insipidus and subsequent
      hypopituitarism masking a suprasellar germinoma in a 13-year-old girl.
AB  - CASE REPORT: We report a case of central diabetes insipidus, hypothyroidism, and
      subsequent hypopituitarism due to lymphocytic hypophysitis masking a germinoma in
      a 13-year-old pubertal girl. Magnetic resonance revealed an enlarged pituitary
      gland and a mass lesion in the pituitary stalk and inferior hypothalamus. Open
      cranial surgery of the anterior pituitary showed active hypophysitis with
      lymphocytic infiltrates but without necrosis. Despite prednisolone therapy, 1
      year later an enlarged, irregular cystic mass lesion had developed; in the
      pituitary stalk and inferior hypothalamus, a endoscopic biopsy revealed
      germinoma. CONCLUSION: Lymphocytic hypophysitis in children may be the first sign
      of a host reaction to an occult germinoma. The diagnosis of central diabetes
      insipidus with a thickened pituitary stalk requires long-term follow-up to
      establish the underlying cause.

PMID- 16565856
TI  - Michael Trede.

PMID- 16565854
TI  - Modified technique of hepatic vascular exclusion: effect on blood loss during
      complex mesohepatectomy in hepatocellular carcinoma patients with cirrhosis.
AB  - BACKGROUND: Hepatic veins remain patent during complete inflow occlusion (CIO)
      and bleeding from them may continue. Occlusion of the inferior vena cava (ICV)
      during CIO may reduce blood loss from hepatic veins. This study was designed to
      compare the overall outcomes after application of CIO with or without occlusion
      of the ICV below the liver in complex mesohepatectomy for hepatocellular
      carcinoma (HCC) patients with cirrhosis. MATERIALS AND METHODS: One hundred and
      eighteen (118) patients were randomly assigned to CIO or a modified technique of
      hepatic vascular exclusion (MTHVE). Hemodynamic parameters were evaluated and the
      amount of blood loss, measurement of liver enzymes, and postoperative progress
      were recorded. RESULTS: Blood loss during liver transection in CIO groups was
      significantly greater than that in MTHVE group (P=0.046). Thus, incidence of
      blood transfusion was significantly greater in patients of the CIO group
      (P=0.041). There were no significant differences in liver enzyme changes,
      bilirubin, or morbidity in the postoperative period between the two groups.
      CONCLUSIONS: CIO with occlusion of the ICV below the liver is a safe, effective,
      and feasible technique during mesohepatectomy in HCC patients with cirrhosis.
      Excellent results were obtained with minimized bleeding, limited hepatic function
      damage, and low rate of postoperative complications.

PMID- 16565853
TI  - Infantile clivus chordoma without clivus involvement: case report and review of
      the literature.
AB  - BACKGROUND: We present a giant clival chordoma with disseminated disease but
      without involvement of the clivus. To our knowledge, this is the youngest child
      and only the second case, presenting without base of skull involvement, in
      paediatric literature and the fourth reported case of a chordoma in a patient
      with tuberous sclerosis. DISCUSSION: We discuss the subtle presentation,
      difficulties in diagnosis and management and also review the literature.

PMID- 16565857
TI  - Isolation and transduction of monocytes: promising vehicles for therapeutic
      arteriogenesis.
AB  - BACKGROUND AND AIMS: Augmentation of collateral vessel growth (arteriogenesis) is
      of particular clinical interest for the treatment of vascular occlusive disease.
      Monocytes play a key role for arteriogenesis. They localize to areas of
      collateral development and create a highly arteriogenic environment. "Homing" of
      ex vivo genetically engineered monocytes could therapeutically be exploited for
      augmentation of arteriogenesis. However, isolation and ex vivo transduction of
      monocytes is problematic. METHODS: In this study, we established a valid method
      of monocyte isolation from peripheral blood and evaluated different in vitro
      transduction methods. RESULTS: Our results revealed that liposomes and
      electroporation were unsuccessful for monocyte transduction. However, high
      efficiency gene transfer (almost 95%) was achieved by adenoviral infection.
      Subsequent homing of virally transduced monocytes to sites of arteriogenesis
      could be demonstrated. CONCLUSION: Our study may offer a new method for the
      augmentation of arteriogenesis, all of which makes the ultimate goal of applying
      this strategy to humans for therapy of vascular disease eminently attractive.

PMID- 16565858
TI  - Radiofrequency induced thermotherapy: an alternative palliative treatment
      modality in head and neck cancer.
AB  - Bipolar radiofrequency induced thermotherapy (RFITT) is a minimally invasive
      electrosurgical technique characterized by a precise controllable effect in the
      tissue. It has demonstrable efficacy, safety and reproducibility in the
      management of solid malignancies. Our aim was to assess the morbidity and
      efficacy of RFITT as a palliative treatment of head and neck cancer. Prospective,
      non-randomized case series and analysis. After evaluation by the
      multidisciplinary Head and Neck Tumour Board at Helsinki University Central
      Hospital, Finland, 12 consecutive patients with a head and neck cancer without
      curative treatment possibilities were enrolled into the study. Five patients had
      pharyngeal carcinomas, one had an unknown primary tumour growing through the skin
      on the neck, two had a recurrent malignant melanoma originating from the
      maxillary sinuses, one had a carcinoma of the tongue, two had laryngeal
      carcinomas, and one had a recurrent adenoid cystic carcinoma of the parotid
      gland. RFITT was performed with a CelonLabPrecision generator using appropriate
      electrodes. The treatment was administered under local or general anaesthesia.
      The subjective morbidity of the treatment was evaluated. The response to the
      treatment was assessed clinically and with radiological imaging when feasible.
      All but two of the patients received palliation to their disease. RFITT induced
      clinically a partial response in ten patients, and there were radiological
      detectable changes. There were no treatment related complications, and the
      patients tolerated the treatment well. RFITT in head and neck cancer patients is
      easy to perform, well tolerated, and induces reduction in the tumour mass.
      Continuous evaluation of RFITT treatment modality is warranted in selected
      palliative care patients.

PMID- 16565859
TI  - Mannose selection system used for cucumber transformation.
AB  - The selectable marker system, which utilizes the pmi gene encoding for
      phosphomannose-isomerase that converts mannose-6-phosphate to fructose-6
      phosphate, was adapted for Agrobacterium-mediated transformation of cucumber
      (Cucumis sativus L.). Only transformed cells were capable of utilizing mannose as
      a carbon source. The highest transformation frequency of 23% was obtained with 10
      g/l mannose and 10 g/l sucrose in the medium. Molecular, genetic analysis, and
      PMI activity assay showed that the regenerated shoots contained the pmi gene and
      the gene was transmitted to the progeny in a Mendelian fashion. The results
      indicated that the mannose selection system, which is devoid of the disadvantages
      of antibiotic or herbicide selection, could be used for cucumber Agrobacterium
      mediated transformation.

PMID- 16565860
TI  - Stability of transgene integration and expression in subsequent generations of
      doubled haploid oilseed rape transformed with chitinase and beta-1,3-glucanase
      genes in a double-gene construct.
AB  - A double-gene construct with one chitinase and one beta-1,3-glucanase gene from
      barley, both driven by enhanced 35S promoters, was transformed into oilseed rape.
      From six primary transformants expressing both transgenes 10 doubled haploid
      lines were produced and studied for five generations. The number of inserted
      copies for both the genes was determined by Southern blotting and real-time PCR
      with full agreement between the two methods. When copy numbers were analysed in
      different generations, discrepancies were found, indicating that at least part of
      the inserted sequences were lost in one of the alleles of some doubled haploids.
      Chitinase and beta-1,3-glucanase expression was analysed by Western blotting in
      all five doubled haploid generations. Despite that both the genes were present on
      the same T-DNA and directed by the same promoter their expression pattern between
      generations was different. The beta-1,3-glucanase was expressed at high and
      stable levels in all generations, while the chitinase displayed lower expression
      that varied between generations. The transgenic plants did not show any major
      impact on fungal resistance when assayed in greenhouse, although purified beta
      1,3-glucanase and chitinase caused retardment of fungal growth in vitro.

PMID- 16565861
TI  - Artificial synthesis of interspecific chimeras between tuber mustard (Brassica
      juncea) and cabbage (Brassica oleracea) and cytological analysis.
AB  - Interspecific chimeras between tuber mustard and red cabbage were obtained by in
      vitro graft-culture method. Before grafting, 6-day-old seedlings of tuber mustard
      and red cabbage were vertically half-cut and treated with different
      concentrations of 6-BA and NAA for 1 min, then, they were symmetrically fit
      together. As a result, sectorial chimeras were initially produced from the united
      shoot tips. The maximum frequency of chimeral bud formation reached 6.33% when
      the vertical sections of tuber mustard and cabbage were treated with 2 mg/l 6-BA
      and 1 mg/l NAA. When sectorial chimeras were propagated on MS medium containing 1
      mg/l 6-BA, periclinal and mericlinal chimeras gradually developed. Chimeral
      shoots were rooted on half-strength MS medium containing 0.1 mg/l NAA. The rooted
      chimeras were acclimatized and transferred to the field for cytological and
      morphological analysis. The results showed that stomata density in the chimeras
      was significantly higher than that of their parents, while chloroplast size,
      starch grain size and number were intermediate between the two parents. The
      chimeras were further analyzed by flow cytometry, and the results indicated that
      they contained both sets of parental chromosomes. Moreover, chimeral plants
      possessed valuable characters from the two parents.

PMID- 16565863
TI  - A new locus for dominant hereditary spastic paraplegia maps to chromosome 2p12.

PMID- 16565862
TI  - Cenp-F (mitosin) is more than a mitotic marker.
AB  - Cenp-F (mitosin) is a large coiled-coil protein whose function has remained
      obscure since its identification a decade ago. It has been suggested that the
      protein plays a role in the kinetochore-mediated mitotic functions but until
      recently there was little evidence to support this postulation. Recent results
      from five laboratories have given insights on how Cenp-F may participate in the
      regulation of cell division. In this mini-review, we will summarize the current
      data regarding the mitotic tasks of Cenp-F as well as discuss how it is used as a
      proliferation marker of malignant cell growth in the clinic. Also, the protein's
      post-translational modification by farnesylation and potential contribution to
      cell cycle effects of farnesyl transferase inhibitors will be addressed.

PMID- 16565864
TI  - Heterogeneous oxygenation in nonexercising triceps surae muscle during
      contralateral isometric exercise.
AB  - To test whether changes in oxygenation of a resting skeletal muscle, evoked by a
      static contraction in a contralateral muscle, is uniform within a given skeletal
      muscle, we used near-infrared spectroscopy (NIRS). Seven subjects performed 2 min
      static knee extension exercise at 30% of maximal voluntary contraction. Changes
      in oxygenated hemoglobin (HbO(2)) were monitored using multiple-channel NIRS (40
      channels, 13 sources and 12 detectors) attached on the contralateral
      nonexercising triceps surae muscle. Changes in HbO(2) were expressed as a
      percentage of total labile signals. To characterize the distribution of changes
      in HbO(2), channels were compared between their positions on the triceps surae
      muscle, and represented as 'proximal versus distal' and 'lateral versus medial'
      portions. During static muscle contraction, the averaged changes in HbO(2) of all
      channels were correlated with those in calf blood flow (plethysmography; R
      (2)=0.188, P<0.05) and with calf vascular conductance (R (2)=0.146, P<0.05).
      HbO(2) did not differ significantly between the lateral and medial portions of
      the triceps surae muscle. In contrast, the decrease of HbO(2) in the proximal
      portion of the muscle was greater than that of the distal portion (P<0.05). These
      results indicate that the changes in oxygenation of a resting muscle, evoked by
      static contraction of the contralateral muscle, are heterogeneous.

PMID- 16565865
TI  - Fas-ligand-expressing adenovirus-transfected dendritic cells decrease allergen
      specific T cells and airway inflammation in a murine model of asthma.
AB  - T cells expressing a type-2 T helper profile of cytokines (Th2 cells) have been
      demonstrated to play an important role in the initiation and progression of
      allergic asthma, and it is well known that Fas ligand (FasL) induces apoptosis
      when bound to its receptor, Fas. In the present study, we examined the
      possibility of modulating asthma manifestations by dendritic cells (DCs)
      genetically engineered to express FasL (DC-FasL), which could deliver a death
      signal to T cells in an antigen-specific manner. The delivery of DC-FasL into
      ovalbumin (OVA)-immunized allergic mice decreased the airway hyper-responsiveness
      (AHR). Moreover, we established a mouse model of airway inflammation by using an
      adoptive transfer of Th2 cells derived from ovalbumin T cell receptor transgenic
      mice to study the effect of DC-FasL on airway reactivity. The administration of
      DC-FasL in Th2-cell-induced allergic mice had significantly decreased AHR, airway
      inflammation, and IL-4, IL-5 and IL-13 production. Furthermore, the numbers of
      OVA-specific T cells were decreased in the lung of mice receiving DC-FasL. These
      results demonstrate that FasL-expressing dendritic cells might be applied for the
      modulation of allergic responses.

PMID- 16565866
TI  - Association between sleep apnea severity and blood coagulability: Treatment
      effects of nasal continuous positive airway pressure.
AB  - A prothrombotic state may contribute to the elevated cardiovascular risk in
      patients with obstructive sleep apnea (OSA). We investigated the relationship
      between apnea severity and hemostasis factors and effect of continuous positive
      airway pressure (CPAP) treatment on hemostatic activity. We performed full
      overnight polysomnography in 44 OSA patients (mean age 47+/-10 years), yielding
      apnea-hypopnea index (AHI) and mean nighttime oxyhemoglobin saturation (SpO2) as
      indices of apnea severity. For treatment, subjects were double-blind randomized
      to 2 weeks of either therapeutic CPAP (n = 18), 3 l/min supplemental nocturnal
      oxygen (n = 16) or placebo-CPAP (<1 cm H2O) (n = 10). Levels of von Willebrand
      factor antigen (VWF:Ag), soluble tissue factor (sTF), D-dimer, and plasminogen
      activator inhibitor (PAI)-1 antigen were measured in plasma pre- and
      posttreatment. Before treatment, PAI-1 was significantly correlated with AHI (r =
      0.47, p = 0.001) and mean nighttime SpO2 (r = -0.32, p = 0.035), but these OSA
      measures were not significantly related with VWF:Ag, sTF, and D-dimer. AHI was a
      significant predictor of PAI-1 (R2 = 0.219, standardized beta = 0.47, p = 0.001),
      independent of mean nighttime SpO2, body mass index (BMI), and age. A weak time
      by-treatment interaction for PAI-1 was observed (p = 0.041), even after adjusting
      for age, BMI, pre-treatment AHI, and mean SpO2 (p = 0.046). Post hoc analyses
      suggested that only CPAP treatment was associated with a decrease in PAI-1 (p =
      0.039); there were no changes in VWF:Ag, sTF, and D-dimer associated with
      treatment with placebo-CPAP or with nocturnal oxygen. Apnea severity may be
      associated with impairment in the fibrinolytic capacity. To the extent that our
      sample size was limited, the observation that CPAP treatment led to a decrease in
      PAI-1 in OSA must be regarded as tentative.

PMID- 16565867
TI  - The role of telemedicine in CPAP compliance for patients with obstructive sleep
      apnea syndrome.
AB  - The objective of this study was to compare continuous positive airway pressure
      (CPAP) use, functional status, and client satisfaction in obstructive sleep apnea
      syndrome (OSAS) patients randomized to either telemedicine support or traditional
      care. In our university-affiliated sleep disorders center, patients with OSAS who
      were initiating CPAP therapy were randomized to receive telemedicine support vs
      traditional follow-up care for 30 days. The telemedicine group received a "Health
      Buddy" computer that provided daily Internet-based informational support and
      feedback for problems experienced with CPAP use. At 30 days, there were no
      significant differences in the hours of CPAP use between groups receiving
      traditional care (M = 4.22, SD+/-2.05) and telemedicine support (M = 4.29, SD+/
      2.15), p = 0.87, or in the proportion of nights with CPAP use between the
      traditional (M = 50%+/-33.8) and telemedicine groups (M = 47%+/-34.2), p=0.61. No
      significant differences were found between groups in functional status (M =
      2.27+/-4.56 vs M = 2.03+/-3.88, respectively, p = 0.76) or client satisfaction (M
      = 28.0+/-3.51 vs M = 28.5+/-3.05, p = 0.43). Patients in the telemedicine and
      traditional groups had similar CPAP use, functional status, and client
      satisfaction. The data suggest that telemedicine support as provided by our model
      compares favorably with traditional care. As a provider-extender, telemedicine
      support for patients initiating use of CPAP may allow for greater practice
      efficiency while maintaining quality of care.

PMID- 16565868
TI  - Hyponatremia in Kawasaki disease.
AB  - Although hyponatremia frequently occurs in Kawasaki disease (KD), the clinical
      characteristics of KD patients with hyponatremia and the pathogenesis of
      hyponatremia in KD remain unknown. The aims of this study were to define the
      clinical characteristics of KD patients with hyponatremia (serum sodium <135
      mEq/l) and to determine the factors associated with its development. One hundred
      and fourteen patients with KD were included in this study. Fifty-one patients
      (44.7%) had hyponatremia. Coronary artery lesions and dehydration were
      significantly more common in patients with hyponatremia. The duration of fever
      was significantly longer in patients with hyponatremia. Pyuria and hematuria were
      present significantly more often in patients with hyponatremia. The serum
      concentrations of potassium, chloride and total cholesterol were significantly
      lower in patients with hyponatremia. Serum C-reactive protein and alanine
      aminotransferase were significantly higher in patients with hyponatremia. Some
      patients with pyuria and hyponatremia exhibited increased excretion of urinary
      tubular epithelial cells and urinary casts. There was no difference in the
      incidence of diarrhea between patients with hyponatremia and patients without
      hyponatremia. These results indicate that hyponatremia in KD occurs in patients
      exhibiting severe inflammation. Further studies will be necessary to confirm the
      pathogenic mechanisms of hyponatremia in patients with KD.

PMID- 16565869
TI  - Foetal kidney maldevelopment in maternal use of angiotensin II type I receptor
      antagonists.
AB  - We report renal lesions observed in a foetus exposed throughout pregnancy to
      angiotensin II type I (AT 1) receptor antagonists. The mother suffered from
      essential hypertension and was treated with Cozaar (losartan 50 mg). Autopsy
      examination of the foetus revealed severe renal lesions, including tubular
      dysgenesis, hypertrophy of the endothelial and medial cells lining the arterial
      and arteriolar walls, hyperplasia of the juxtaglomerular apparatus and poorly
      developed vasa recta. Similar lesions have already been observed in foetuses of
      women treated with angiotensin-converting enzyme antagonists and also in foetuses
      and neonates of animals undergoing experimental blockade of the renin-angiotensin
      system. The purpose of this report is to describe structural lesions observed in
      the kidneys, and, particularly, vascular lesions. Our results suggest that the
      use of AT 1 receptor antagonists during pregnancy may have a severe deleterious
      effect on kidney development in the foetus.

PMID- 16565870
TI  - Left ventricular hypertrophy and arterial wall thickening in children with
      essential hypertension.
AB  - OBJECTIVE: Our aim was to determine the prevalence of left ventricular
      hypertrophy (LVH) and increased intima-media thickness (IMT) in Caucasian
      children with newly diagnosed, untreated essential hypertension (EH).
      PARTICIPANTS: Our study cohort consisted of 72 children with EH (mean age: 14.5
      years; range: 5-18 years). The control groups consisted of 103 age-matched,
      healthy children. METHODS: We evaluated the left ventricular mass (LVM), intima
      media thickness in the carotid (cIMT) and superficial femoral (fIMT) arteries, 24
      h ambulatory blood pressure, and biochemical cardiovascular risk factors.
      RESULTS: Of the hypertensive children examined, 41.6% had LVM above the 95th
      percentile, and 13.2% had LVM above 51 g/m2.7. Of the hypertensive subjects, the
      cIMT was above 2 SDS of normal values in 38.8%, and the flMT was above 2 SDS of
      normal values in 17.5%. Patients with LVM above 51 g/m2.7 had a higher birth
      weight than other patients. LVM, cIMT, and fIMT correlated with 24-h SBP and
      pulse pressure; LVM also correlated with homocysteine and serum uric acid
      concentrations. fIMT correlated with low Aprotein A1 (ApoA1), higher ApoB and C
      reactive protein, and daily sodium excretion. Step-wise regression analysis
      revealed that serum uric acid and higher birth weight were predictors for LVM,
      pulse pressure was a predictor for cIMT, and ApoB was a predictor for fIMT.
      CONCLUSIONS: A significant number of adolescents with EH already had
      cardiovascular damage at diagnosis. LVM and markers of arterial injury correlate
      with SBP, biochemical, and perinatal cardiovascular risk factors. Serum uric acid
      and higher birth weight are predictors of LVM.

PMID- 16565871
TI  - The use of darbepoetin in infants with chronic renal impairment.
AB  - Darbepoetin is a newer analogue of epoetin, with a longer half-life, that allows
      less frequent administration. There are currently no published data available for
      its use in infants. We report our experience with this drug in infants with
      chronic renal impairment, weighing less than 8 kg. Infants had baseline
      haemoglobin (Hb), iron, ferritin and transferrin levels measured. They were
      started on approximately 0.5 microg/kg per week of darbepoetin. Hb levels were
      checked every 2-4 weeks, and iron studies were performed every 4 weeks. Iron
      supplementation was prescribed to maintain ferritin levels>100 microg/l and
      transferrin saturation levels>20%. Follow up was for 20 weeks. Six infants with a
      mean weight of 4.08 kg and a mean creatinine of 259 micromol/l were included.
      Three infants were medically stable throughout the study, and the mean
      darbepoetin dose was decreased to 0.25 microg/kg per week. Their dosing interval
      was increased to every 3-4 weeks. The other three infants were less stable and
      had multiple medical problems, including periods of haemodialysis and surgery.
      These infants failed to reach target Hb level, despite an increase in the mean
      dose of darbepoetin to 1.2 microg/kg per week. In conclusion, darbepoetin can be
      successfully administered to infants with chronic renal insufficiency, but the
      dose needs to be tailored to each individual. Administration would be facilitated
      by smaller unidose syringes.

PMID- 16565872
TI  - Nitric oxide and superoxide in rat mesangial cells: modulation by C-reactive
      protein.
AB  - BACKGROUND: C-reactive protein (CRP) has been linked to cardiovascular and renal
      disease. We evaluated the effects of CRP on the production of nitric oxide (NO)
      and superoxide by rat mesangial cells (RMC) and the impact on cell function.
      METHODS AND RESULTS: RMC were incubated with cytokines (IFN-gamma, IL-1beta, and
      LPS) and CRP (10-100 microg/ml) for 24-72 h. Exposure to CRP resulted in a time-
      and dose-dependent reduction in NO accumulation (p<0.05). Although inducible
      nitric oxide synthase (iNOS) protein expression was unaltered after 48 h, CRP
      stimulated expression of HSP90. Steady state abundance of iNOS mRNA increased
      nearly threefold after a 24-h exposure to CRP. Incubation with 100 microg/ml CRP
      for 60-120 min resulted in a 272% increase in superoxide production that was
      prevented by diphenyleneiodium chloride but not L-NAME (p<0.0001). CONCLUSION:
      CRP enhances superoxide release in RMC, which in turn inactivates NO and reduces
      net production. The functional relevance of these CRP-induced changes is
      supported by increased expression of HSP90 in RMC exposed to the mediator. These
      findings suggest that systemic inflammation, which contributes to the
      pathogenesis of atherosclerosis, may play a role in the progression of kidney
      disease.

PMID- 16565873
TI  - Ten-year results of randomized treatment of children with severe vesicoureteral
      reflux. Final report of the International Reflux Study in Children.
AB  - For the comparison of long-term outcome of the management of medical or surgical
      treatment of children with severe vesicoureteral reflux (VUR), children aged <11
      years with non-obstructive grade III/IV reflux, previous urinary tract infection
      (UTI) and glomerular filtration rate (GFR) >or=70 ml/min per 1.73 m2 body surface
      area were recruited, and 306 were randomly allocated to receive antimicrobial
      prophylaxis or ureteral reimplantation. Primary endpoints were new renal scars
      and renal growth. Follow up, originally planned for 5 years, was extended to 10
      years for 252 children, 223 of whom had follow-up imaging. Up to 5 years, 40 new
      urographic scars (medical 19, surgical 21) were seen. Between 5 years and 10
      years, only two further scars were observed. Renal growth and UTI recurrence rate
      were similar, except that medically treated patients had more febrile infections.
      There was no difference in somatic growth, radionuclide imaging or renal
      function. A GFR <70 ml/min per 1.73 m2 was found in only one patient. Three
      patients developed hypertension requiring treatment. We conclude that, with close
      supervision and prompt treatment of recurrences, children entering the study with
      GFR >or=70 ml/min per 1.73 m2 progressed remarkably well under either medical or
      surgical management, emphasizing the importance of continued supervision and the
      entry level of renal function.

PMID- 16565874
TI  - Bladder dysfunction in children and adolescents after renal transplantation.
AB  - The underlying mechanisms of urinary-tract infections (UTI) in renal transplant
      recipients are still not fully understood. In otherwise healthy children, bladder
      dysfunction increases the susceptibility to UTI. The aim of this study was to
      evaluate lower-urinary-tract function in children and adolescents after renal
      transplantation. Sixty-eight recipients of renal transplants, 5-20 years of age
      and 1-15 years after transplantation, were evaluated for their bladder function
      with a questionnaire, uroflowmetry and bladder ultrasound, and for renal function
      (glomerular filtration rate) by measuring clearance of inulin or iohexol. Forty
      nine patients (72%) had some type of abnormality of bladder function. Abnormal
      bladder capacity was found in 26%, abnormal urinary flow in 50% and residual
      urine in 32% of the patients. There was no significant difference in bladder or
      renal function in children with urinary-tract malformations compared with those
      with normal urinary tract. Furthermore, there was no significant difference in
      renal function in patients with bladder dysfunction compared with those without.
      The incidence of bladder dysfunction is high in children and adolescents after
      renal transplantation, but the clinical significance of this finding and whether
      there is a correlation between bladder dysfunction and UTI in these patients need
      to be clarified further.

PMID- 16565875
TI  - Inflammatory pseudotumor of the cavernous sinus and skull base.
AB  - Inflammatory pseudotumor is a non-neoplastic process of unknown etiology
      characterized by a proliferation of connective tissue with an inflammatory
      infiltrate. Intracranial inflammatory pseudotumors classically involve the
      cavernous sinus but can also occur in the supratentorial or infratentorial
      compartments and spinal canal. Symptoms are dependent on location, and, when
      present in the cavernous sinus, typically include cranial nerve palsies of those
      nerves in the cavernous sinus. These lesions are rapidly responsive to steroid
      therapy. Surgery is typically indicated for biopsy only, but complete resection
      may be justified for lesions outside the cavernous sinus.

PMID- 16565877
TI  - Functional outcome following reconstruction in chronic multiple ligament
      deficient knees.
AB  - Multiligament knee injuries are rare but potentially limb-threatening conditions.
      In this study we aim to evaluate the mid- and long-term functional outcome of
      patients who underwent arthroscopically assisted multiple ligament reconstruction
      for chronic multiple knee ligament deficiency. Thirty-five patients (27 males and
      8 females) with an average age of 35.1 years (range: 17-60) were included in this
      study. Follow-up ranged from 12 to 124 months (average: 40.3). On final follow-up
      patients had a mean loss of extension of 3.1 degrees , while flexion ranged from
      95 degrees to 135 degrees (average: 118.4 degrees ). The functional outcome
      according to Clancy's criteria was excellent in 7 patients (20%), good in 14
      (40%), fair in 11 (31.4%), while 3 reconstructions resulted in failure (8.6%).
      Patients scored an average of 4.03 (range: 1-9) in their Tegner Activity Scale,
      while their score in Activities of Daily Living Scale of the Knee Outcome Survey
      ranged from 25 to 98 with an average of 72.7. Sixteen patients returned to
      sporting activities and all but three returned to work. Early operative treatment
      of multiple ligament injuries is preferable, as it may allow for anatomic repair
      instead of reconstruction of ligamentous structures. This study demonstrates
      though, that even if acute reconstruction has not or could not be performed,
      reconstruction in chronic multiple ligament deficient knees should be attempted.
      Although this complex and technically demanding procedure rarely results in a
      "normal" knee, it offers in most cases very satisfactory stability and a
      significant improvement in knee function.

PMID- 16565876
TI  - Interaction of the epithelial Ca2+ channels TRPV5 and TRPV6 with the intestine-
      and kidney-enriched PDZ protein NHERF4.
AB  - The epithelial Ca(2+) channels TRPV5 and TRPV6 constitute the apical Ca(2+)
      influx pathway in epithelial Ca(2+) transport. PDZ proteins have been
      demonstrated to play a crucial role in the targeting or anchoring of ion channels
      and transporters in the apical domain of the cell. In this study, we describe the
      identification of NHERF4 (Na-P(i) Cap2/IKEPP/PDZK2) as a novel TRPV5- and TRPV6
      associated PDZ protein. NHERF4 was identified using two separate yeast two-hybrid
      screens with the carboxyl termini of TRPV5 and TRPV6 as bait. Binding of the
      carboxyl termini of TRPV5 and TRPV6 with NHERF4 was confirmed by GST pull-down
      assays using in-vitro-translated NHERF4 or lysates of Xenopus laevis oocytes
      expressing NHERF4. Furthermore, the interaction was confirmed by GST pull-down
      and co-immunoprecipitation assays using in-vitro-translated full-length TRPV5 and
      Xenopus oocytes or HEK293 cells co-expressing NHERF4 and TRPV5/TRPV6,
      respectively. The fourth PDZ domain of NHERF4 was sufficient for the interaction,
      although PDZ domain 1 also contributed to the binding. The binding site for
      NHERF4 localized in a conserved region in the carboxyl terminus of TRPV5 and was
      distinct from the binding site of the PDZ protein NHERF2. NHERF4 predominantly
      localized at the plasma membrane of X. laevis oocytes and HeLa cells. This
      localization was independent of the presence of TRPV5. Therefore, we hypothesize
      a role for this novel PDZ protein as a putative plasma membrane scaffold for the
      epithelial Ca(2+) channels.

PMID- 16565878
TI  - Knee kinematics and kinetics during gait, step and hop in males with a 16 years
      old ACL injury compared with matched controls.
AB  - The objective of this study was to compare subjects who sustained an ACL injury
      during soccer 16 years ago with a control group with regard to knee kinematics
      and kinetics of gait, step activity and cross over hop. Secondly, in the injured
      subjects, the purpose was to study the impact on kinematics and kinetics of
      characteristics such as operative status, meniscal resection, being symptomatic,
      having knee extensor weakness and of having radiographic knee OA. Data from a 3
      dimensional gait analysis system (VICON) were used to calculate kinetics and
      kinematics during gait, step activity and cross over hop of 12 male subjects who
      had an anterior cruciate ligament injury 16 years earlier. Twelve uninjured
      subjects matched for age, sex, BMI and activity level served as controls. No
      significant differences in knee kinematics and kinetics between the ACL group and
      the control group were found. The variability of some parameters of step and all
      parameters of hop activity was generally larger in the ACL injured subjects
      compared with the controls. The ACL injured subjects had a significantly worse
      clinical status compared with the controls. Reduced knee extension strength was
      associated with joint moment reductions especially during step activity and cross
      over hop. Despite a significantly worse clinical status, as determined by self
      report and isokinetic strength testing, no significant differences were seen in
      knee joint kinetics and kinematics in an ACL injured group 16 years after injury
      compared with a matched control group. The variation was larger among the ACL
      injured subjects indicating the need for larger study groups in gait and movement
      analysis in long-term follow-up of ACL injury.

PMID- 16565879
TI  - Mobile versus fixed-bearing total knee arthroplasty: mid-term comparative
      clinical results of 216 prostheses.
AB  - Since the late 1970s, mobile-bearing total knee designs have been advocated as
      having theoretical advantages over fixed-bearing total knee replacements. At
      present there is no consensus as to whether there are any differences in clinical
      results between the two designs. We present the results of two consecutive
      cohorts each of over 100 prosthesis. The first cohort underwent a fixed-bearing
      prosthesis, whilst the second cohort received the mobile bearing variant of the
      same prosthesis. Both groups were assessed pre- and post-operatively using the
      American Knee Society knee and function scores as well as range of movement and
      the presence or absence of anterior knee pain. No difference was found
      statistically significant between the groups, either for the knee score
      (P=0.068), the function score (P=0.26), the range of movement (P=0.11) or the
      proportions of anterior knee pain (P=0.06). It is our opinion that mobile bearing
      knee prosthesis have still to prove their theoretical advantages in clinical
      practice.

PMID- 16565880
TI  - Sibling risk of pervasive developmental disorder estimated by means of an
      epidemiologic survey in Nagoya, Japan.
AB  - Broad-spectrum autism, referred to as pervasive developmental disorder (PDD), may
      be associated with genetic factors. We examined 241 siblings in 269 Japanese
      families with affected children. The sibling incidence of PDD was 10.0% whereas
      the prevalence of PDD in the general population in the same geographic region was
      2.1%. Both of these rates are higher than those reported previously, probably
      because of the expanded clinical criteria applied. The prevalence in males of the
      general population was 3.3% and that in females was 0.82%. The sibling incidences
      were 7.7 and 20.0% for families in which the probands were male and female,
      respectively. Because the reversed sex ratios correspond to the general rule for
      a multifactorial threshold model, we suggest that most PDD cases result from the
      cumulative effects of multiple factors (mostly genetic). The sibling incidences
      were 0 and 10.9% for families in which the proband had low and normal birth
      weight, respectively, suggesting the risk is lower in families with low-birth
      weight probands.

PMID- 16565881
TI  - Complete sequence data support lack of balancing selection on PRNP in a natural
      Chinese population.
AB  - The M129V mutation in the human prion protein gene (PRNP) is the primary site
      linked to susceptibility to prion diseases in humans. The heterozygous state of
      this allele has been proven to be more resistant to prion-related diseases such
      as Creutzfeldt-Jakob disease. Based on a study of the common genetic variations,
      it has been proposed that balancing selection has played a critical role in
      shaping the distribution of 129V in worldwide populations. Kreitman and Di-Rienzo
      [Kreitman and Di-Rienzo (2004)Trend Genet 20:300-304] challenged this hypothesis
      by pointing out that the exclusion of polymorphisms with low frequency may
      introduce an ascertainment bias and, in turn, lead to a wrong conclusion. By
      studying sequence variations in samples from the Human Genome Diversity Project,
      Soldevila et al. [Soldevila et al. (2005) Trends Genet 21:389-391] showed that
      this ascertainment bias does exist. We argue that the evidence presented by
      Soldevila et al. may be compromised by the samples tested since they were
      selected from a population that may be substructured. In this study, we re
      evaluated the hypothesis of balancing selection in a natural Chinese population
      using a much longer segment encompassing the entire genomic region of the PRNP
      gene (15 kb). We showed that the pattern of genetic variation in PRNP is not
      consistent with the presence of balancing selection in this gene.

PMID- 16565882
TI  - Analysis of the physiological mechanism of salt-tolerant transgenic rice carrying
      a vacuolar Na+/H + antiporter gene from Suaeda salsa.
AB  - Salt stress is one of the most serious factors limiting the productivity of
      agricultural crops. Increasing evidence has demonstrated that vacuolar Na+/H+
      antiporters play a crucial role in plant salt tolerance. In the present study, we
      expressed the Suaeda salsa vacuolar Na+/H+ antiporter SsNHX1 in transgenic rice
      to investigate whether this can increase the salt tolerance of rice, and to study
      how overexpression of this gene affected other salt-tolerant mechanisms. It was
      found that transgenic rice plants showed markedly enhanced tolerance to salt
      stress and to water deprivation compared with non-transgenic controls upon salt
      stress imposition under outdoor conditions. Measurements of ion levels indicated
      that K+, Ca2+ and Mg2+ contents were all higher in transgenic plants than in non
      transformed controls. Furthermore, shoot V-ATPase hydrolytic activity was
      dramatically increased in transgenics compared to that of non-transformed
      controls under salt stress conditions. Physiological analysis also showed that
      the photosynthetic activity of the transformed plants was higher whereas the same
      plants had reduced reactive oxygen species generation. In addition, the soluble
      sugar content increased in the transgenics compared with that in non-transgenics.
      These results imply that up-regulation of a vacuolar Na+/H+ antiporter gene in
      transgenic rice might cause pleiotropic up-regulation of other salt-resistance
      related mechanisms to improve salt tolerance.

PMID- 16565884
TI  - Normal physiological emotions but differences in expression of conscious feelings
      in children with high-functioning autism.
AB  - To provide insight into what aspects of the emotional circuit might be affected
      in high-functioning autism, we measured indices of physiological emotions and of
      the expression of conscious feelings in 10 children with high-functioning autism
      or Asperger syndrome and 10 comparison participants. Pleasant, unpleasant, and
      neutral pictures were presented while skin conductance responses were measured.
      Self-report ratings of pleasantness and interestingness were taken between
      pictures. Skin conductance responses did not differ between the groups. Self
      report ratings were different, with the children with autism giving more similar
      answers to the two questions than the comparison children. Impairments in socio
      emotional expression in autism may be related to deficits in perception and/or
      expression of conscious feelings; physiological emotions may be relatively
      preserved.

PMID- 16565883
TI  - Pharmacodynamic models for agents that alter production of natural cells with
      various distributions of lifespans.
AB  - Indirect pharmacodynamic response (IDR) models were developed for agents which
      alter the generation of cell populations with arbitrary lifespan distributions.
      These models extend lifespan based IDR models introduced previously [J.
      Pharmacokinet. Biopharm. 27: 467, 1999] for cell populations with the same
      lifespan ("delta" distribution). Considered are cell populations exhibiting time
      invariant lifespan distributions described by the probability density function
      l(tau). It is assumed that cell response (R) is produced at a zero-order rate
      (kin(t)) and is eliminated from the population when the cell lifespan expires.
      The cell loss rate is calculated as kin*l(t), where '*' denotes the convolution
      operator. Therapeutic agents can stimulate or inhibit production rates according
      to the Hill function: 1 +/- H(C(t)) where H(C(t)) contains the capacity (Smax)
      and potency (SC50) parameters and C(t) is a pharmacokinetic function. The
      production rate is kin(t) = kin.[ 1+/-H(C(t))]. The operational model is dR/dt =
      kin(t)-kin*l(t) with the baseline condition R0 = kin.TR, where TR is the mean
      lifespan. Single populations as well as populations with precursors were examined
      by simulation to establish the role of lifespan distribution parameters (mean and
      standard deviation) in controlling the response vs. time profile. Estimability of
      parameters was assessed. Numerical techniques of solving differential equations
      with the convolution integral were proposed. In addition, the models were applied
      to literature data to describe the stimulatory effects of single doses of
      recombinant human erythropoietin on reticulocytes in blood. The estimates of Smax
      and SC50 for these agents were obtained along with means and standard deviations
      for reticulocyte lifespan distributions. The proposed models can be used to
      analyze the pharmacodynamics of agents which alter natural cell production
      yielding parameters describing their efficacy and potency as well as means and
      standard deviations for cell lifespan distributions.

PMID- 16565885
TI  - 1998-2002 Update on "Causes of death in autism".

PMID- 16565886
TI  - The efficacy of behavioral treatments for hypertension.
AB  - Evidence is reviewed for the efficacy of behavioral treatments for hypertension.
      The format chosen here is a review of reviews given that numerous consensus
      committee reports and quantitative reviews on the topic have been published.
      Extensive evidence from over 100 randomized controlled trials indicates that
      behavioral treatments reduce blood pressure (BP) to a modest degree, and this
      change is greater than what is seen in wait-list or other inactive controls.
      Effect sizes are quite variable. The observed BP reductions are much greater when
      BP levels were high at pre-test, and behavioral studies tend to underestimate
      possible benefits because of floor effects in their protocols. Blood pressure
      measured in the office may be confounded with measurement habituation. Multi
      component, individualized psychological treatments lead to greater BP changes
      than do single-component treatments. Among biofeedback treatments, thermal
      feedback and electrodermal activity feedback fare better than EMG or direct BP
      feedback, which tend to produce null effects. There continues to be a scarcity of
      strong protocols that properly control for floor effects and potential
      measurement confounds.

PMID- 16565887
TI  - Relationship between adolescent marijuana use and young adult illicit drug use.
AB  - : We examined three components of the "gateway theory" in relation to marijuana
      use: (1) whether adolescent marijuana use predicts young adult drug use, (2)
      whether this association persists when controlling for similar family background,
      (3) whether common genetic or environmental factors contribute to the
      association. The three components were tested in adolescents from the National
      Longitudinal Study of Adolescent Health assessed twice during adolescence and
      then re-interviewed 5 years later. Component 1 was tested in 18,286 subjects,
      component 2 in sibling pairs (n=360) discordant for marijuana use, and component
      3 in a genetically informative sub-sample (n=4846). Marijuana use was defined as
      any use during adolescence, and drug use was defined as self-reported past year
      use of other illicit drugs besides marijuana. Marijuana users were twice as
      likely to use illicit drugs as young adults than non-users. Shared environmental
      factors mediated much of the relationship between adolescent marijuana use and
      young adult drug use. The association remained, however, even when controlling
      for familial environmental and other measured factors.

PMID- 16565888
TI  - The development of physical aggression from toddlerhood to pre-adolescence: a
      nation wide longitudinal study of Canadian children.
AB  - The objectives of the study were to model the developmental trajectories of
      physical aggression (PA) from toddlerhood to pre-adolescence and to identify risk
      factors that distinguish typical (normative) from atypical developmental
      patterns. Ten cohorts of approximately 1,000 children (n = 10,658) drawn form a
      nationally representative (Canadian) sample were followed over 6 years. Using a
      group based trajectory approach, we identified three groups of children with
      distinct developmental trajectories between 2 and 11 years of age. One third of
      the children (31.1%) followed a low desisting trajectory, reflected in infrequent
      use of PA in toddlerhood and virtually no PA by pre-adolescence. The majority of
      children (52.2%) followed a moderate desisting trajectory, reflected in
      occasional use of PA in toddlerhood and infrequent use by pre-adolescence. One
      sixth of the children (16.6%) followed a high stable trajectory of PA.
      Multivariate logistic regression indicated that children in the high PA
      trajectory group were more likely to be boys (OR: 1.67; CI: 1.5-1.87), from low
      income families (OR: 1.4; CI; 1.27-1.67), from families where the mother had not
      completed high school (OR: 1.20; CI: 1.05-1.38) and who reported using
      hostile/ineffective parenting strategies (OR: 1.16; CI: 1.14-1.18). In sum, the
      results indicate that the typical developmental pattern of PA was one of
      occasional and declining use over time. However, about one sixth of children,
      mostly boys from disadvantaged families, exhibited an atypical developmental
      pattern reflected in more frequent and stable use of PA. The results suggest that
      most children learned relatively well to inhibit PA by the end of childhood and
      that a minority failed to do so. Family risks traditionally found to be
      associated with antisocial behaviors during adolescence appear to interfere with
      the socialization of PA during early and middle childhood.

PMID- 16565889
TI  - A rare disorder: idiopathic tumoral calcinosis.

PMID- 16565890
TI  - Could 2'5'-oligoadenylate synthetase isoforms be biomarkers to differentiate
      between disease flare and infection in lupus patients? A pilot study.
AB  - 2'5'-Oligoadenylate synthetase (OAS) was shown to be related to systemic lupus
      erythematosus (SLE) 20 years ago, and was rediscovered to be involved in type I
      interferon pathway in SLE by several microarray gene expression studies recently.
      The goal of this study was to investigate OAS isoform expressions in lupus
      patients, to evaluate whether they could become biomarkers to differentiate
      between disease flare and infection. Fifty-four SLE patients presented with fever
      or systemic inflammatory syndrome, or both, were enrolled. Gene expressions of
      OAS1, OAS2, and OASL were studied by using real time PCR in active SLE (SLEDAI
      >or=9, n=29) and in those complicated with infections (n=25). The latter group
      was composed of 19 patients with invasive bacterial infections, and six patients
      with viral infections. C reactive protein (CRP) and other clinical parameters
      were also measured. Twenty-nine healthy individuals made up a normal control
      group. The mRNA expressions of OAS1, OAS2, and OASL were higher in patients with
      lupus flares than those with infections (p<0.03), or normal controls (p<0.001).
      SLE complicated with infections have higher OAS1 expression level (P=0.002),
      lower OASL (P=0.004), and equivalent OAS2 (P=0.135), when compared with those of
      normal controls. OASL expression level was negatively correlated with infection
      in lupus by logistic regression analysis (p=0.008). Area under the receiver
      operating characteristic curve for the prediction of infection was 0.92
      (p<0.0001) for OASL, and 0.77 (p=0.007) for CRP. Therefore, our preliminary data
      suggest that the pattern of OAS isoform expressions, OASL in particular, may
      provide useful information in differentiating disease flares from certain
      infections in SLE.

PMID- 16565891
TI  - Camptocormia as a clinical manifestation of mitochondrial myopathy.
AB  - Camptocormia is an unusual condition characterized by a progressive weakness of
      the extensor muscles of the spine that cause an involuntary truncal flexion.
      Occasionally, camptocormia can be the clinical manifestation of an underlying
      myopathy, including inflammatory or metabolic myopathies. We present a case of a
      78-year-old female with camptocormia associated with a mitochondrial myopathy.
      Additionally, we review the clinical characteristics of three similar, previously
      reported cases.

PMID- 16565892
TI  - Dietary calcium and bone mineral density in premenopausal women with systemic
      lupus erythematosus.
AB  - The primary objective of this study was to determine the relationship between
      dietary calcium intake and bone mineral density (BMD) in premenopausal women with
      systemic lupus erythematosus (SLE) on corticosteroids (CS). The secondary aim was
      to identify other risk factors for osteoporosis in these patients. A cross
      sectional sample of patients attending the SLE Clinic at a teaching hospital was
      recruited. BMD was measured using dual-energy X-ray absorptiometry. Daily dietary
      calcium intake was assessed using a structured validated food frequency
      questionnaire, in which patients were asked to estimate their food intake based
      on their recent 2-month dietary habits. Sixty subjects were recruited with a mean
      age of 33.70+/-8.46 years. The median duration of CS use was 5.5 years (range
      0.08-24). The median cumulative dose of steroids was 17.21 g (range 0.16-91.37).
      The median daily dietary calcium intake was 483 mg (range 78-2101). There was no
      significant correlation between calcium intake and BMD, even after correcting for
      CS use. There were also no correlations between BMD and the duration of SLE,
      cumulative CS use, duration of CS use, smoking, alcohol intake, and SLE disease
      activity index score. Twenty-eight (46.7%) patients had normal BMD, 28 (46.7%)
      had osteopenia, and four (6.6%) had osteoporosis. Duration of SLE significantly
      correlated with cumulative CS dosage. In conclusion, 6.7% of these Asian
      premenopausal SLE women had osteoporosis and only 46.7% had normal BMD. Daily
      dietary calcium intake did not correlate with BMD.

PMID- 16565893
TI  - Leukocytapheresis for the treatment of refractory systemic-onset juvenile
      idiopathic arthritis.
AB  - Although leukocytapheresis (LCAP) has been reported to be effective for the
      treatment of various autoimmune disorders, little information has been published
      yet on the efficacy and safety of LCAP for the treatment of systemic-onset
      juvenile idiopathic arthritis (SOJIA). A pilot trial of LCAP was therefore
      conducted on two children with refractory SOJIA using a granulocyte apheresis
      filter packed with cellulose acetate beads in an attempt to control the disease
      flares. Following three to eight sessions of LCAP, the joint symptoms gradually
      resolved without any increase in the dose of corticosteroids. The procedure was
      associated with a decrease in the serum interleukin-6. No severe adverse effects
      were observed except for mild nausea. However, efficacy of LCAP sustained in a
      short time since both patients subsequently developed flares after 3 months of
      the treatment.

PMID- 16565894
TI  - Comparison of the effect of alendronate on lumbar bone mineral density and bone
      turnover in men and postmenopausal women with osteoporosis.
AB  - The purpose of the present study was to compare the effect of alendronate
      treatment on lumbar bone mineral density (BMD) and bone turnover in men and
      postmenopausal women with osteoporosis. Sixty men with primary or secondary
      osteoporosis and 318 women with postmenopausal osteoporosis were treated with
      alendronate. The primary end points were lumbar BMD and urinary cross-linked N
      terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase
      (ALP) levels. The secondary end point was the incidence of vertebral and
      nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could
      complete the 12-month trial were analyzed. The mean ages of men and
      postmenopausal women were 69.1 and 70.4 years, respectively. Both men and
      postmenopausal women showed higher levels of urinary NTX as compared with normal
      range of premenopausal women. Alendronate treatment decreased urinary NTX level
      by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level
      by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone
      turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal
      women, respectively, at 12 months. Reduction in urinary NTX level and increase in
      lumbar BMD were smaller in men than in postmenopausal women. The incidence of
      vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and
      8.3 and 7.5%, respectively, in postmenopausal women, with no significant
      difference in these incidences between them. These results suggested that
      alendronate treatment effectively increased lumbar BMD from baseline in men with
      primary or secondary osteoporosis following reduction in bone turnover, although
      its efficacy did not appear to be greater than in postmenopausal women with
      osteoporosis.

PMID- 16565895
TI  - The occurrence of systemic lupus erythematosus in an asymptomatic carrier of
      human T-cell lymphotropic virus type I.
AB  - A 63-year-old asymptomatic carrier of human T-cell lymphotropic virus type I
      (HTLV-1) infection was admitted because of chest oppression, a high-grade fever,
      polyarthralgia, and erythematous rashes. Laboratory examination revealed
      lymphocytopenia, proteinuria, and high titers of antinuclear antibodies and
      antidouble-stranded DNA antibody; thus, she was diagnosed as having systemic
      lupus erythematosus (SLE). This case indicates that HTLV-1 infection might be
      related with the pathogenesis of SLE.

PMID- 16565896
TI  - Oxidative status in rheumatoid arthritis.
AB  - The insufficiency of antioxidant defense systems and the acceleration of the
      oxidative reactions can be results of the pro-oxidant/antioxidant imbalance in
      rheumatoid arthritis (RA). The aim of our study was to investigate the changes in
      oxidant status by measuring two different parameters; one was the level of
      malondialdehyde (MDA) as an index of lipid peroxidation and the other was total
      oxidative status; we could then compare our results with the antioxidant status,
      superoxide dismutase (SOD) enyzme activities. All were assessed in 22 patients
      with active RA and 18 age- and gender-matched control subjects. While serum MDA
      levels were significantly increased in patients with RA compared to the control
      group (p<0.03), the total oxidative status levels were decreased in patients with
      RA compared to the control group (p<0.008), and serum SOD activities did not show
      any statistical difference between the two groups. In conclusion, the increased
      MDA levels in our study may be important as a marker but are not sufficient to
      conclude that there was an increase in oxidative stress in RA patients because
      supporting results were not obtained from SOD and oxidative status measurements.
      These results give further support to the concept of oxygen free radicals playing
      a role in the pathogenesis of chronic inflammatory disorders, but we also
      consider that there is a more complex relationship than has been assumed. We
      think that further studies are needed to clarify these conflicting results.

PMID- 16565897
TI  - Safety and efficacy of infliximab in a patient with active WHO class IV lupus
      nephritis.
AB  - Because disease activity in systemic lupus erythematosus correlates well with
      increased serum levels and activity of the cytokine tumor necrosis factor alpha
      (TNF-alpha), we report on the safety and efficacy of infliximab, a chimeric
      monoclonal antibody directed against TNF-alpha, given to a patient with active
      lupus with diffuse proliferative nephritis (WHO Class IV). This patient who
      failed to remit with a combination of full-dose steroids, mycophenolate mofetil,
      and cyclosporine, went into sustained remission with the addition of infliximab
      infusions.

PMID- 16565898
TI  - Remitting seronegative symmetrical synovitis pitting oedema after BCG
      instillation.
AB  - Remitting seronegative symmetrical synovitis pitting oedema (RS3PE) is a distinct
      form of seronegative rheumatoid arthritis like polyarthritis. It is characterized
      by late onset symmetrical joint involvement and pitting oedema of hands and feet
      (JAMA 254(19):2763-2767, [1]). Polyarthritis secondary to intravesical Bacillus
      Calmette Guerin (BCG) therapy has been reported (Clin Rheumatol 21:536-537, [2]).
      To our knowledge, about 0.5% of patients receiving BCG instillation presented
      polyarthritis, but only one case of RS3PE has been reported (J Rheumatol 28:1699
      1701, [3]). We described the second case of RS3PE following intravesical BCG
      instillation of bladder carcinoma.

PMID- 16565899
TI  - Racial and ethnic disparities in mortality following congenital heart surgery.
AB  - Our objective was to assess risk-adjusted racial and ethnic disparities in
      mortality following congenital heart surgery. We studied 8483 congenital heart
      surgical cases from the Kids' Inpatient Database 2000. Black sub-analysis was
      performed using predetermined regional categories. For our Hispanic sub-analyses,
      we categorized Hispanics into state groups according to a state's predominant
      Hispanic group: West (Mexican-American), Southeast (Cuban-American), Northeast
      (Puerto Rican), and Mixed/Heterogeneous. Risk adjustment was performed using the
      Risk Adjustment for Congenital Heart Surgery method. Multivariate analyses
      assessed the effect of race/ethnicity and Hispanic state group on mortality and
      explored the effects of gender, income, insurance type, and region. Black
      children had a higher risk for death than Whites odds ratio (OR), [1.65; p =
      0.003]. Hispanics and the Cuban-American state group showed a trend toward a
      higher death risk (Hispanic: OR, 1.24; p = 0.16; Southeast Cuban-American: OR
      1.55; p = 0.08). Disparities were not influenced by insurance. Among Blacks,
      disparities were greatest in the Northeast region (OR, 2.25; p = 0.007). After
      adjusting for gender, income, and region, Blacks (OR, 1.76; p = 0.002) and
      Hispanics (OR, 1.34; p = 0.05) had a higher death risk. Racial and ethnic
      disparities in risk-adjusted mortality following congenital heart disease exist
      for Blacks and Hispanics. These disparities are not due to insurance but are
      partially explained by gender and region.

PMID- 16565900
TI  - Delayed contrast enhancement magnetic resonance imaging in congenital aortic
      stenosis.
AB  - We report a case of a 12-year-old boy with severe congenital aortic stenosis in
      whom magnetic resonance imaging (MRI) with delayed contrast enhancement
      demonstrated extensive subendocardial hyperenhancement within the left ventricle.
      The hyperenhancement was confirmed to be subendocardial infarct and fibrosis by
      histopathology. This case supports the utility of MRI with delayed contrast
      enhancement in evaluating myocardial viability in patients with congenital heart
      disease.

PMID- 16565901
TI  - Persistent truncus arteriosus with double aortic arch.
AB  - We report a rare association of persistent truncus arteriosus with double aortic
      arch in a 34-day old neonate.

PMID- 16565902
TI  - Two young adults who had acute coronary syndrome after regression of coronary
      aneurysms caused by Kawasaki disease in infancy.
AB  - We report two young adult patients who had acute coronary syndrome after
      regression of coronary aneurysms caused by Kawasaki disease (KD). A 26 year-old
      man had acute anterior myocardial infarction at midnight after drinking alcohol.
      He had had bilateral coronary aneurysms caused by KD at the age of 8 months.
      Selective coronary angiograms (CAGs) at the age of 7 years revealed regression of
      both coronary aneurysms. He had no symptoms until the onset of acute myocardial
      infarction. The other patient was a 24 year-old man diagnosed as having a
      subendocardial infarction. He had had bilateral coronary aneurysms caused by KD
      at the age of 1 year. CAGs at the age of 9 years showed that both had regressed.
      It should be recognized that young adults with apparently normal coronary
      arteries angiographically after regression of large coronary aneurysms caused by
      KD may occasionally have acute coronary syndromes. We suspect intimal involvement
      of the coronary arterial wall after regression of the large aneurysms underlies
      the acute coronary syndrome in adults. Risk factors for atherosclerosis must be
      avoided in this population.

PMID- 16565903
TI  - Prevalence of interatrial septal aneurysm in newborns and their natural course.
AB  - The objective of this study was to evaluate the prevalence of atrial septal
      aneurysm (ASA) in newborns, to define the natural course of ASA, and to
      investigate its role on closure of associated interatrial septal opening (IASO).
      A total of 1072 consecutive neonates were examined with echocardiography in the
      early postnatal period. The length of the interatrial septum, the diameter of
      IASO, the excursion and base of aneurysm, and the width of the related atrium
      were measured and the excursion ratio and the basal ratio were calculated for
      each neonate. Aneurysms with an excursion ratio > or = 25% were diagnosed as ASA.
      There were 81 neonates (7.6%) with ASA. The prevalence of ASA was 11.1% in
      preterm (14 of 126) and 7.1% in full-term newborns (67 of 946). All of the ASAs
      disappeared at the end of the first year of life, and there were no complications
      related to the lesion during the follow-up period. Although overall IASO
      prevalence was 78.6% (843 of 1072), it was 72.8% (59 of 81) among the cases with
      ASA. Although the disappearance time of interatrial septal shunt was not
      significantly different between the cases with and without ASA, spontaneous
      closure was less frequent in the cases with ASA than in those without ASA 77.7
      and 96.1%), respectively (p < 0.001). The prevalence of ASA is high among
      newborns, with a high resolution rate. Therefore, it can be considered that it is
      benign and transient observation. Less frequent spontaneous closure of IASO in
      cases with ASA indicates that ASA may have a deleterious effect on spontaneous
      closure.

PMID- 16565904
TI  - Resection of an obstructive neonatal cardiac myxoma of the infundibulum.
AB  - Myxoma, the most common primary cardiac tumor in adults, is rare in neonates. We
      describe a myxoma arising from the infundibulum of the right ventricle causing
      significant outflow tract obstruction in an otherwise normal newborn. Serial
      echocardiograms revealed an increasing gradient across the right ventricular
      outflow tract prompting surgery. The patient underwent successful excision of the
      myxoma with an uneventful recovery.

PMID- 16565905
TI  - Persistent atrial standstill in noncompaction cardiomyopathy.
AB  - Atrial standstill is a rare form of bradyarrhythmia and consists of a transitory
      or permanent loss of the electrical and mechanical activity of the atria. It has
      been described in a few cases of long-standing valvular disease, amyloidosis,
      myocarditis, and muscular dystrophy. We report on a young female with
      noncompaction cardiomyopathy that progressed to congestive heart failure.
      Electrocardiogram showed persistence atrial standstill that was confirmed
      clinically and by electrocardiomyopathy, Doppler two-dimensional echocardiogram,
      and tissue Doppler imaging. We assume that worsening of asymptomatic
      noncompaction and progression to the congestive form of cardiomyopathy could be
      presaged by the presence of persistent atrial standstill. Thus, persistence of
      atrial standstill in asymptomatic cardiomyopathy is a sign of poor prognosis.

PMID- 16565906
TI  - Altered prostaglandin E1 dosage during extracorporeal membrane oxygenation in a
      newborn with ductal-dependent congenital heart disease.
AB  - We describe a neonate with ductal-dependent congenital heart disease on
      extracorporeal membrane oxygenation (ECMO) for persistent pulmonary hypertension,
      who required markedly high doses of prostaglandin E1 (PGE1) to maintain patency
      of the ductus arteriosus: The effects of ECMO on the pharmacokinetics of PGE1 are
      discussed.

PMID- 16565907
TI  - Tetralogy of Fallot with congenital aortic valvar stenosis: the tetralogy-truncus
      interrelationship.
AB  - Two rare patients are reported with tetralogy of Fallot and congenital aortic
      valvar stenosis. The anatomic and developmental interrelationship between
      tetralogy of Fallot and truncus arteriosus is summarized. A study of 100 randomly
      selected postmortem cases of tetralogy revealed aortic valve pathology in 8%,
      myxomatous aortic valve leaflets without stenosis in 4%, bicuspid aortic valves
      without stenosis in 3%, and congenital aortic valvar stenosis in 1%. The
      frequency of systemic semilunar valve pathology in truncus was much higher (66%):
      moderate to marked myxomatous change in 44%, mild myxomatous change in 22%,
      truncal valvar stenosis in 11%, and truncal valvar regurgitation in 15%. Being
      aware of the tetralogy-truncus interrelationship and knowing that myxomatous
      aortic valves are prone to premature calcific aortic stenosis and/or
      regurgitation, physicians should follow the aortic valves of surgically repaired
      patients with tetralogy of Fallot and truncus arteriosus long term with great
      care. Timely aortic valvuloplasty or replacement may well prove life-saving in
      such patients.

PMID- 16565908
TI  - Hemodynamic and electrocardiographic effects of early pulmonary valve replacement
      in pediatric patients after transannular complete repair of tetralogy of Fallot.
AB  - In adults, pulmonary value replacement (PVR) shows improvement in right
      ventricular (RV) volume and function and reduces QRS duration. In addition, RV
      volume correlates with QRS duration and QRS change. This has not been shown in
      pediatric patients. The purpose of this study was to evaluate serial magnetic
      resonance imaging (MRI) and electrocardiogram measurements before and after early
      PVR in a pediatric population with repaired Tetralogy of Fallot and whether QRS
      duration and QRS change correlated with RV volume. A retrospective review of MRIs
      and electrocardiograms was conducted on 10 patients. Median age at repair was 2.1
      +/- 0.7 years, and median age at PVR was 11.5 +/- 2.0 years. There were
      significant decreases in RV end diastolic volume (EDV)/body surface area (BSA) (p
      < 0.0004), end systolic volume (ESV)/BSA (p = 0.02), RVEDV/left ventricular (LV)
      EDV (p < 0.001), RV ejection fraction (p < 0.04), RV stroke volume (SV)/BSA (p <
      0.0002), and (RVSV - LVSV)/BSA (p = 0.0007). No significant change in QRS
      duration occurred (p = 0.08). QRS duration (pre-r = 0.44, p = 0.20; post-r =
      0.34, p = 0.33) and QRS change (r = -0.08, p = 0.83) did not correlate with
      RVEDV. We propose early consideration of PVR in pediatric patients. PVR improves
      RV volumes and function and may provide beneficial electromechanical effects by
      slowing the progression of QRS duration.

PMID- 16565909
TI  - Magnetic resonance imaging of a distorted left subclavian artery course: an
      important clue to an unusual type of double aortic arch.
AB  - The objective of this study was to determine if distortion of the left subclavian
      artery course distinguishes double aortic arch with atretic left dorsal aorta
      from right aortic arch with mirror image branching. We performed a retrospective
      case series at a tertiary care center. Twenty-six patients undergoing magnetic
      resonance imaging for suspicion of a vascular ring were identified, 6 of whom had
      an atretic left dorsal aorta confirmed by surgical inspection. Six patients with
      the diagnosis of right aortic arch with mirror image branching were identified
      for comparison. The course of the left subclavian artery was assessed using
      surface-rendered magnetic resonance angiography (MRA) and axial fast spin echo
      images. All patients with double aortic arch had clinical symptoms suggestive of
      esophageal or tracheal compression. Six patients had double aortic arch, 3 of
      whom had an atretic left dorsal aorta. In these 3 patients, the branching
      patterns on MRA mimicked right aortic arch mirror image branching except for the
      distortion of the initial course of the left subclavian artery. Surgical
      observation confirmed the presence of an atretic left dorsal aorta that resulted
      in tension on the left subclavian artery pulling it posteriorly and inferiorly
      and completing the vascular ring. Patients with right aortic arch mirror image
      branching demonstrated no such subclavian artery distortion, and these patients
      did not have clinical symptoms suggestive of a vascular ring. Our results
      demonstrate that left subclavian artery distortion due to traction by an atretic
      left arch is an important diagnostic finding in the evaluation 6 patients with
      suspected vascular rings.

PMID- 16565910
TI  - 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography/computed tomography
      imaging evaluation of esophageal cancer.
AB  - We evaluated the clinical utility of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)
      positron emission tomography (PET)/computed tomography (CT) on the precise
      localization of pathologic foci and exclusion of normal variants in the imaging
      evaluation of patients with esophageal carcinoma. Combined PET/CT scans were
      performed in 60 patients (50 males, 10 females, age range 47-84 years) with
      history of esophageal carcinoma either at the time of initial diagnosis (group I,
      n=14) or for surveillance and/or detection of recurrent and metastatic disease
      (group II, n=46). Prior treatments included esophagectomy with gastric pull-up
      (n=23), surgery and chemotherapy (n=3), surgery and chemoradiation therapy
      (n=10), chemotherapy alone (n=5), radiation therapy alone (n=2), and
      chemoradiation without surgery (n=3). Diagnostic validation was by tissue
      sampling in three patients and clinical/radiological follow-up for up to 1.5
      years in the remaining patients. In group I, discordant abnormalities were noted
      in seven patients. PET demonstrated hypermetabolism in normal-size lymph nodes on
      CT in three patients that were considered likely true positive in view of
      concurrent existence of other adjacent enlarged hypermetabolic lymph nodes in the
      same nodal basin. Hypometabolic incidental CT abnormalities of up to 1-cm lung
      nodules were noted in three patients and pleural effusion in one patient, which
      were considered true negative in view of no change on follow-up PET/CT studies.
      In group II, both PET and CT showed concordant abnormalities in 23 patients. The
      precise image fusion of hypermetabolism in a liver lesion allowed a diagnostic CT
      guided biopsy in one patient. PET demonstrated true positive hypermetabolic
      abnormalities in four patients that localized to structures, which were normal by
      noncontrast CT criteria, and true negative in one patient with hepatic fatty
      deposits. PET showed decline in metabolic activity of the primary lesion in one
      patient after chemotherapy, while the corresponding CT abnormality remained
      unchanged. PET/CT image fusion provided relevant complementary diagnostic
      information in 14 patients with discordant findings (23% of total) that resulted
      in biopsy in three cases, institution of chemotherapy in four cases, and a wait
      and-watch strategy in seven cases. In conclusion, our findings add to the current
      body of literature that suggests that FDG-PET/CT scanning may improve the imaging
      evaluation of patients with esophageal cancer by providing complementary
      structural-metabolic information. In particular, our findings support the notion
      that PET/CT may be the most appropriate imaging modality in the evaluation of
      patients of esophageal cancer that may impact patient management.

PMID- 16565911
TI  - Short-term effects of psychiatric symptoms and interpersonal stressors on
      criminal violence--a case-crossover study.
AB  - BACKGROUND: The aim of the study was to analyse the triggering or acute risk
      effect of psychiatric symptoms and interpersonal stressors on criminal violence.
      METHOD: One hundred and thirty three violent offenders were recruited from a
      forensic psychiatric evaluation (FPE) unit and a national prison evaluation unit
      in Sweden during 2002-2003, and were interviewed about trigger exposures. A case
      crossover design was used eliminating long-term within individual confounding.
      RESULTS: Suicidal ideation or parasuicide within 24 h before the violent event
      conferred a ninefold risk increase. In contrast, violent ideation did not trigger
      criminal violence. Hallucinations yielded a fourfold risk increase, whereas
      paranoid thoughts were associated with a small and statistically non-significant
      risk increase. Acute conflicts with others and being denied psychiatric care
      within 24 h before violence also increased the risk of acting violently.
      CONCLUSIONS: Some tested psychiatric symptoms and stressors triggered criminal
      violence, whereas others did not. The case-crossover design may be particularly
      useful for the study of triggers of violence.

PMID- 16565913
TI  - Gender, place, and method of suicide.
AB  - BACKGROUND: The goal of the study was to investigate whether women use less
      lethal methods in committing suicide than men. A related objective was to
      determine whether place of committing suicide influences method of suicide.
      METHOD: Data on all completed suicides occurring in Riverside County from 1998 to
      2001 were derived from original death certificates obtained from records of the
      County Coroner. Descriptive statistics on method and place of suicide by sex were
      computed and graphically presented. Multivariate logistic regression models were
      fitted to data on 643 suicide victims to estimate the unique effects of sex and
      place of suicide on the three most common methods observed: firearms, hanging,
      and drug poisoning. RESULTS: Women were over 73% less likely to use firearms than
      men (OR = 0.267, CI = 0.172, 0.413). There were no sex differentials in hanging.
      Female victims were over 4 times more likely to die from drug poisoning than male
      victims (OR = 4.828, CI = 3.047, 7.650). When place of committing suicide was
      added to the equation, it was found that victims killing themselves at home were
      over 2.5 times as likely to use firearms as those dying in outdoor settings (OR =
      2.501, CI = 1.078, 6.051). Persons committing suicide at home were over 3 times
      more likely to hang themselves than those killing themselves outdoors or on
      railway tracks (CI = 3.118, CI = 1.447, 6.718). Victims committing suicide at
      home were also 3 times as likely to use drugs as those dying outdoors or on
      railway tracks (OR = 3.118, CI = 1.242, 7.828). Hotel or motel suicides were 4.9
      times more likely to use drug poisoning than outdoor or railway suicides (OR =
      4.924, CI = 1.409, 17.206). CONCLUSIONS: The proposition that women use less
      lethal methods of committing suicide than men was only partially supported by the
      data. It appears that the situation is more complex than a simple dichotomy
      between more lethal and less lethal methods. In past research, hanging has been
      considered a very lethal method. However, women were just as likely to hang
      themselves as men. Furthermore, firearm use was the second mode of suicide among
      women. The overall policy implication of this study is that suicide prevention
      efforts should concentrate not only on dissuading potential suicide victims, but
      also limiting access to firearms and promoting responsible firearm storage
      practices.

PMID- 16565912
TI  - Psychosocial risk clustering in high school students.
AB  - BACKGROUND: This secondary analysis describes the frequency of self-reported
      psychosocial risk factors in a geographically defined population of adolescents
      and quantifies the extent of multiple risks. Cluster analysis is used to develop
      three empirically distinct psychosocial risk clusters. METHODS: High school
      students in grades 9-13 from all seven public and two catholic high schools in
      the study area completed a class-administered survey. The analysis is based on
      3540 surveys reflecting approximately a 71% response. Cumulative risk was
      calculated by summing the number of times students exceeded a pre-defined
      threshold on a series of global rating scales. Risk clusters were created using a
      non-hierarchical cluster analysis technique for binary data. Clusters were
      partially validated by examining differences in socio-demographic and health
      utilization patterns. Reliability was assessed by examining two, three, and four
      group solutions across gender and grade strata. RESULTS: Multiple symptoms of
      emotional distress were reported by 37% of the sample, multiple stressors by 62%
      of the sample, and poly-drug use by 33%. In addition, three empirically distinct
      clusters were derived. Normals, 21% of the sample, did not report excessive
      stress or distress, and did not use substances. The Stressed (45%) reported
      excessive stress and distress predominantly related to schoolwork, parents, and
      facing problems. Virtually none used drugs. Substance Users (34%) reported
      excessive stress, distress, and high levels of substance use: smoking, drinking,
      and use of illicit drugs. Clusters were significantly different with respect to
      most socio-demographic factors, self-reported general health, and most aspects of
      health service utilization suggesting that they have some validity for targeting
      programs. CONCLUSIONS: This study highlights the importance of focusing on multi
      morbidities and illustrates the use of cluster analysis to identify risk profiles
      that may be amenable to school-based health promotion and prevention programs.

PMID- 16565914
TI  - Monitoring of mental health systems and services: comparison of four existing
      indicator schemes.
AB  - BACKGROUND: A public mental health indicator scheme may be defined as a
      systematic collection of brief proxy measures that represent summary information
      on variables that are potentially influenced by or relevant to mental health
      systems, programmes and services. Existing public mental health indicator schemes
      have been developed in or for high-income countries. METHOD: The paper describes
      and compares four existing high-income country public mental health indicator
      schemes and highlights key observations. RESULTS: The range of indicators and
      subclasses of indicators covered by the four existing schemes is large. There was
      only one item (indicator) that was covered by more than one scheme. CONCLUSIONS:
      The variety of possibilities in indicators and types of indicators suggests a
      lack of consensus in the essential contents of an indicator scheme. There is a
      need for a public mental health indicator scheme that is applicable in resource
      poor countries.

PMID- 16565915
TI  - Training patients with schizophrenia with the community re-entry module: a
      controlled study.
AB  - BACKGROUND: There is increasing evidence indicating that the Community Re-entry
      Module (CRM), a brief, structured instrument, could guide an effective
      intervention for patients with schizophrenia. This study evaluated the
      effectiveness of the Chinese version of the CRM with respect to improvement in
      psychiatric symptoms, social functioning as well as relapse and re
      hospitalization rates in comparison with a supportive counseling (SC)
      intervention. METHOD: Ninety-six outpatients with DSM-IV schizophrenia were
      randomly allocated to either CRM (N=48) or an equally intensive intervention of
      SC (N=48). The CRM was composed of 16 one-hour sessions, which were conducted
      with groups of 6-8 patients on a twice-a-week schedule. The two groups received
      routine psychiatric outpatient care during the intervention. Participants were
      assessed on an intention-to-treat basis with the Positive and Negative Syndrome
      Scales (PANSS), with the Social Disability Screening Schedule (SDSS) by two
      independent raters before and immediately after intervention, and at 6-month
      follow-up. The number of relapse and re-hospitalization were also documented.
      RESULTS: The CRM group significantly improved in terms of psychiatric symptoms
      and social functioning compared with the SC group. Rates of relapse and re
      hospitalization in the CRM group were lower although the difference between the
      two groups was not statistically significant. CONCLUSIONS: The study supports the
      feasibility and effectiveness of the Chinese version of the CRM as an effective
      psychosocial intervention for Chinese patients with schizophrenia to improve
      psychopathology, social functioning and relapse and re-hospitalization rates.

PMID- 16565916
TI  - Suicide rates, life satisfaction and happiness as markers for population mental
      health.
AB  - OBJECTIVE: To examine the association of variables from survey data on well-being
      with suicide rates and other markers of population mental health in Europe.
      DESIGN: Ecological study correlating (Spearman's rank correlation) life
      satisfaction and happiness (European Values Survey 1999/2000) in 32 countries
      with suicide rates (WHO Mortality Database), rates of hospital discharge for
      mental and behavioural disorders and prevalence of mental disorders based on
      registered mental patients (WHO Regional Office for Europe) and Mental Health
      Index (MHI)-5 survey data (European Opinion Research Group). RESULTS: An inverse
      association exists between suicide rates and life satisfaction (r=-0.44; 95% CI: 
      0.68, -0.11) and happiness (r=-0.42; 95% CI: -0.67, -0.08). Similar though weaker
      associations were seen with hospital discharge data and MHI-5 data but not with
      the prevalence of mental disorders. The association between suicide rates and
      life satisfaction was weaker amongst 15-44 year olds (r=-0.31; 95% CI: -0.59,
      0.04) than amongst 45-64 year olds (r=-0.47; 95% CI: -0.70, -0.14). It was
      strongest in the 65+ age group (r=-0.54; 95% CI: -0.75, -0.23). A similar pattern
      was observed for the association with happiness. In a subgroup analysis, the
      association between suicide and life satisfaction in Eastern Europe was similar
      to that in the whole dataset (r=-0.35) but a positive association was seen in
      Western Europe (r=0.47). CONCLUSIONS: Life satisfaction and happiness were
      modestly associated with other indicators of population mental health. Since all
      such markers have their limitations, surveys of well-being may be useful
      indicators of population mental health.

PMID- 16565917
TI  - Severe and persistent mental illness: a useful definition for prioritizing
      community-based mental health service interventions.
AB  - OBJECTIVE: There is a lack of consensus on the identification of seriously
      mentally ill patients (SMI). This study investigates the external and predictive
      validity of an operationalized definition for the severity and persistency of
      mental illness applied to a sample of service users attending a community mental
      health service. METHOD: The definition is based on the fulfilment of dysfunction
      (GAF < or = 50) and illness duration (> or = 2 yrs) criteria. The study was
      conducted with a two-year longitudinal design. External and predictive validity
      of the SMI definition were assessed against the diagnosis of psychosis. RESULTS:
      Our data show evidence for an overall high predictive and external validity of
      the SMI definition and high sensitivity in predicting those with high burden of
      mental illness. CONCLUSIONS: In order to identify people with high levels of
      psychiatric burden, the SMI working definition seems to be more useful than that
      simply based on diagnostic criteria.

PMID- 16565919
TI  - Suicide mortality and agricultural rationalization in post-war Europe.
AB  - BACKGROUND: The relationship between agricultural rationalization and suicide
      mortality has been little researched. On the basis of the hypothesis that
      agricultural rationalization leads to more suicide, this study investigated
      whether a general relationship could be found between structural change in
      agriculture and suicide mortality in post-war Europe. METHOD: Due to the expected
      small size of the effect, the data were deliberately collected so as to maximize
      the variation in the independent variable. Annual national-level data on suicide
      mortality, the percentage of the work force in agricultural employment, and the
      unemployment level were collected from those countries and 10-year periods where
      the structural changes (reductions in employment) in agriculture between 1950 and
      1995 had been most and least pronounced. In order to avoid confounders, the
      annual changes in the variables' values were correlated with each other, adding a
      control for the level of unemployment, and allowing for lagged effects. RESULTS:
      The annual changes in the levels of agricultural employment and those of suicide
      mortality did not covary at all. Controlling for unemployment levels did not
      change this, nor could any lagged effects be found. CONCLUSIONS: At the most
      general level, no causal relation between agricultural rationalization and
      suicide mortality was detected. This lack of a universal relation does not,
      however, preclude the possibility of the relationship existing given certain
      socio-historical circumstances.

PMID- 16565918
TI  - Perceived need for alcohol, drug, and mental health treatment.
AB  - BACKGROUND: To investigate determinants of perceived need for alcohol, drug, and
      mental (ADM) health treatment and differences in ADM treatment patterns between
      individuals with perceived need and those without. METHODS: We used data from a
      nationally representative telephone survey of 9585 adults conducted in 1997-1998.
      Logistic regression was used to study the determinants of perceived need and the
      correlation between perceived need and any ADM treatment, specialty ADM
      treatment, appropriate care, and medication adherence. RESULTS: Just fewer than
      37% of individuals with an ADM disorder perceived a need for treatment, while
      4.6% of those without an ADM disorder perceived a need for treatment. Women, the
      young and middle aged, the better educated, those with greater emotional support,
      and those with greater psychiatric morbidity were more likely to perceive need
      for ADM services. Perceived need was strongly correlated with receiving ADM
      treatment, although almost 44% of individuals in ADM treatment did not perceive a
      need for treatment. Among individuals in ADM treatment, those with perceived need
      were significantly more likely to receive specialty ADM treatment, but not more
      likely to be treatment adherent, or to receive appropriate care. CONCLUSION:
      Substantial levels of unmet need are likely to persist as long as perceived
      levels of need remain low. Interventions targeting perceived need may hold
      promise for decreasing unmet need.

PMID- 16565920
TI  - Prevalence of behavioural and emotional problems among six-years-old preschool
      children: baseline results of a prospective longitudinal study.
AB  - OBJECTIVE: To study the prevalence of behavioural and emotional problems and the
      scope of symptoms in preschool children. The results serve as baseline in a 4
      year follow-up study. METHOD: The sample consisted of 1887 preschool children who
      started primary level education within 6 months upon data collection. The sample
      represented the complete 1-year intake of all first year primary school children
      in a northern German town of 254,000 residents. The data were collected with
      standardized parent questionnaires. RESULTS: The 6-month prevalence of
      behavioural and emotional symptoms was 12.4%. The overall score for internalizing
      symptoms (INT) was significantly higher than the score for externalizing symptoms
      (EXT). The disturbed children had the highest mean scores on the syndrome scale
      "Anxious or Depressed". CONCLUSIONS: The level of psychopathology in preschool
      children was already as high as levels seen elsewhere in school children. The
      predominant role of INT was unexpected, particularly for boys. The attention of
      child mental health services need to focus on preschool children as on school
      children and on INT as much as on EXT, especially in boys.

PMID- 16565921
TI  - Where have they been? Service use of regular substance users with and without
      abuse and dependence.
AB  - OBJECTIVE: To present lifetime rates of service use for psychological and
      substance use related problems among regular substance users and to examine
      factors associated with service use. METHOD: Data come from a prospective
      longitudinal, epidemiological study of a community sample of adolescents and
      young adults (n = 2548, age 14-24 years at baseline) in Munich, Germany. The
      Munich-Composite International Diagnostic Interview (M-CIDI) was used at baseline
      and at two follow-ups to assess substance use and service use. RESULTS: Cumulated
      lifetime incidence of any substance abuse or dependence was 43.7%. Of those with
      abuse and dependence 23% had ever used any services for psychological or
      substance use related problems. Illicit substance users especially those with
      dependence had the highest rates of lifetime service use (52.1%).
      Psychotherapists and counseling services were contacted most frequently among
      regular substance users over their lifetimes. Utlilisation rates of substance
      abuse services were low (2%). Comorbid anxiety disorders and distressing life
      events were associated with increased lifetime service use. CONCLUSIONS: Only a
      minority of adolescents and young adults with substance use disorders have ever
      sought professional help. Specialized substance abuse services play only a minor
      role. The core role of psychotherapists and non-substance abuse specialized
      services needs critical research attention. Linkages between psychotherapists and
      the substance use service system should be strengthened to detect and intervene
      at early developmental stages of abuse and dependence.

PMID- 16565922
TI  - Personality correlates of outpatient mental health service utilization: findings
      from the U.S. national comorbidity survey.
AB  - OBJECTIVE: The present paper investigated the relationships between several
      personality constructs and the use of outpatient mental health services. METHODS:
      Respondents were from the National Comorbidity Survey (NCS) Part II data set and
      included those with a past-year mood, anxiety, alcohol/substance use disorder
      (n=1750). Bivariate logistic regressions were used to examine associations
      between participants' self-reports of personality traits and outpatient mental
      health service utilization. Similar multivariate analyses were used to
      investigate these associations after adjusting for sociodemographic variables and
      the presence of psychiatric disorders and their comorbidity. RESULTS: The
      bivariate and multivariate analyses revealed significant positive associations
      between outpatient mental health service utilization and both Powerful Others
      Locus of Control and Self-criticism. CONCLUSIONS: These findings suggest that
      personality traits may play a role in treatment seeking behaviors for mental
      health problems over and above the presence of psychiatric disorders alone. The
      assessment of relevant personality constructs has the potential to inform and
      improve treatment outreach efforts.

PMID- 16565923
TI  - Paraoxonase 1 192 and 55 polymorphisms in nephrotic children.
AB  - Human paraoxonase 1 (PON1) is a serum enzyme related to high-density lipoprotein
      which has a major role in preventing oxidative modification of low-density
      lipoprotein. Due to its amino acid substitution PON1 has two genetic
      polymorphisms. These polymorphisms are characterized by the location of glutamine
      (A genotype) and arginine (B genotype) at position 192, and leucine (L genotype)
      and methionine (M genotype) at position 55. Hyperlipidemia and increased lipid
      oxidation in nephrotic syndrome may lead to glomerulosclerosis and progression of
      the glomerular disease. In this study we aimed to investigate PON1 192 and PON1
      55 polymorphisms in children with focal segmental glomerulosclerosis (FSGS) and
      control subjects. The study included 25 children with biopsy-proven FSGS and 30
      healthy controls. We demonstrated a statistically significant difference between
      FSGS patients and control subjects with respect to the distribution of the PON1
      polymorphism. The AA genotype was less frequent and the AB+BB genotype was more
      frequent in FSGS patients than in controls (48 versus 73% for AA genotype and 52
      versus 27% for AB+BB genotype, p<0.05). Distributions of PON1 55 genotypes of
      FSGS and control subjects were also statistically different (76 versus 43% for LL
      genotype and 24 versus 57% for LM+MM genotype, p<0.05) (case-control study,
      dominant model, Fisher's exact test). The distributions of both genotypes in
      subgroups of FSGS (stable renal function versus declining renal function) were
      not statistically different. We conclude in this preliminary study that presence
      of B allele and/or L allele may be risk factors for the development of FSGS in
      children.

PMID- 16565925
TI  - Plaques and tangles and the pathogenesis of Alzheimer's disease.
AB  - Since the earliest descriptions, senile plaques (SP) and neurofibrillary tangles
      (NFT) have been regarded as the pathological hallmarks of Alzheimer's disease
      (AD). Consequently, studies of the morphology, distribution, and molecular
      composition of SP and NFT have played an important role in developing theories as
      to the pathogenesis of AD; the most important being the 'Amyloid Cascade
      Hypothesis (ACH)'. Nevertheless, the significance of SP and NFT to the
      pathogenesis of AD remains controversial. This review examines three questions:
      1) is there a relationship between the lesions and the degree of clinical
      dementia, 2) is the pathogenesis of the NFT linked to that of the SP, and 3) what
      is the relationship of SP and NFT to the pathogenesis of AD? These questions are
      discussed with reference to the morphology and molecular composition of SP and
      NFT, the effects of gene mutations, studies of head injury patients, experimental
      studies involving brain lesions and transgenes, and the degeneration of specific
      anatomical pathways. It was concluded that SP and NFT are not closely related to
      the developing dementia in AD, arise as relatively independent lesions, and may
      be the products of a degenerative process rather than being their cause.

PMID- 16565924
TI  - A genetic algorithm-based, hybrid machine learning approach to model selection.
AB  - We describe a general and robust method for identification of an optimal non
      linear mixed effects model. This includes structural, inter-individual random
      effects, covariate effects and residual error models using machine learning. This
      method is based on combinatorial optimization using genetic algorithm.

PMID- 16565927
TI  - Involvement of immature endothelial cells in vascular alterations in Alzheimer's
      disease.
AB  - The aim of the present study was to investigate ultrastructural features of
      cerebral capillaries and the pattern of new vessel formation in a patient with
      Alzheimer's disease (AD). Recent neuropathological studies have demonstrated that
      patients with AD have cerebrovascular pathology. Using electron microscopy, we
      showed that alterations of the capillaries are a common finding both in vascular
      disease and in AD, suggesting that vascular factors may also play a role in the
      pathogenesis of AD. We also found regionally increased capillary density, and in
      many sections immature endothelial cells lying on the preexisting endothelium
      were present in the lumen of capillaries. These cells might thus contribute to
      the pathological pattern of capillaries. The cytoplasm of immature endothelial
      cells in the patient with AD was characterized by accumulation of amyloid
      fibrils. We suggest that immature endothelial cells may be an important source of
      circulation-derived amyloid in the brain.

PMID- 16565926
TI  - No association between the brain-derived neurotrophic factor 196 G>A or 270 C>T
      polymorphisms and Alzheimer's or Parkinson's disease.
AB  - The brain-derived neurotrophic factor (BDNF) promotes survival, differentiation
      and maintenance of neurons in the central nervous system. BDNF 196 G>A and 270
      C>T polymorphisms have previously been associated with Alzheimer's disease (AD)
      and with Parkinson's disease (PD). To study the role of BDNF 196 G>A and 270 C>T
      polymorphisms in Finnish AD and PD patients we genotyped BDNF 196 G>A and 270 C>T
      polymorphisms in 97 sporadic AD patients, 52 PD patients and 101 control subjects
      with polymerase chain reaction. No associations were found between the genotypes
      studied and AD or PD in Finnish patients. Moreover, no interaction between either
      BDNF polymorphism and the epsilon 4 allele of apolipoprotein E was found. In
      conclusion, it seems that the BDNF gene does not contribute significantly to the
      risk of AD or PD in Finnish patients.

PMID- 16565928
TI  - Teratoma or enterogenous cyst? The histopathological and clinical dilemma in co
      existing occult neural tube dysraphism.
AB  - BACKGROUND: Better understanding of embryology, histopathology and genetics of
      dysraphic conditions have lead to an expansion of this concept to entities with a
      similar microscopic appearance (e.g. enterogenous cysts, colloid cyst of the III
      rd ventricle) or rated among neoplasms (e.g. mature teratoma), creating a certain
      conceptual confusion. Currently the diagnosis of "teratoma" is being substituted
      by "enterogenous cyst" or "teratomatous cyst". AIM OF PAPER: Clarification of
      concepts in this field and presentation of the experience of the Department of
      Neurosurgery of the Children's Memorial Health Institute associated therewith.
      MATERIAL AND METHOD: Since January 1990 through April 2005 we had treated 7
      children with the final diagnosis of "an enterogenous cyst". The mean age of the
      children was 10.5 years and the mean follow-up time was 4.1 years. The study was
      performed by a retrospective analysis of medical records, imaging studies and
      histological preparations. RESULTS: the study group included: 3 cases of type I
      enterogenous cyst, 1 case of type II cyst and 3 cases of type III cyst (in 2
      cases a former diagnosis of "mature teratoma" has been revised). Within this
      follow-up time, a good outcome was obtained in 3 cases, moderate disability - in
      3 cases and severe disability - in 1 case. CONCLUSIONS: (1) Enterogenous cyst
      often co-exists with other dysraphic features; (2) Clinical signs of an
      enterogenous cyst are non-typical and depend on location of the lesion. The
      presence of secreting gastric mucosa may lead to chemical myelitis; (3) Severity
      of the postoperative neurological deficit is due to the developmental nature of
      the lesion and common vascular supply; (4) Late results of treatment are
      satisfactory, provided the lesion is excised radically; (5) Enterogenous cyst may
      be diagnosed in the case of a tumor composed of tissues originating from 1, 2 or
      3 embryonic layers coexisting with dysraphic stigmata, congenital vertebral
      abnormalities or a mediastinal tumor of the same type. Types II and III of
      enterogenous cyst were historically diagnosed as "adult teratoma".

PMID- 16565929
TI  - Chordoid meningiomas of a different histopathological pattern: a report of two
      cases.
AB  - Chordoid meningioma is an uncommon histopathological variant of meningioma with a
      peculiar chordoma-like appearance. Its association with systemic inflammatory
      disorder linked to Castleman's syndrome was confirmed in the majority of young
      patients, however such a relationship in adults remains enigmatic. We report two
      cases of chordoid meningiomas in adult patients without manifestation of
      Castleman's syndrome. One tumour was almost totally composed of chordoma-like
      areas whereas the second one exhibited the unique combination of chordoma- and
      chondroma-like pattern. This is the first description of chordoid meningioma
      combined with extensive cartilaginous metaplasia. Both tumours exhibited
      histological evidence of infiltrative growth, accompanied by a relatively high
      proliferative index within structures of chordoid appearance. The designation of
      the chordoid component in meningioma is very important as this subtype of
      meningioma exhibits a more aggressive biological behaviour and higher risk of
      recurrence.

PMID- 16565930
TI  - The interaction between lung cancer metastases to the brain and their
      surroundings.
AB  - BACKGROUND AND STUDY PURPOSE: due to the fact that an interrelation between
      metastases of lung cancer to the brain and surroundings may influence the
      prognosis, we made attempts to answer the following questions: 1) how is the
      border between the tumour and its surroundings formed? 2) are there any
      differences in the glial and vascular reactivity around different forms of lung
      cancer metastases to the brain? MATERIAL AND METHODS: a neuropathological
      examination has been done on 66 patients (27 women and 39 men) with lung cancer
      metastases to the brain. They were divided into three groups: group I - 18 cases
      of squamous cell lung cancer (sqclc), group II - 33 cases of lung adenocarcinoma
      (adl) and group III - 15 cases of small cell lung cancer (sclc). RESULTS: the
      most "aggressive" mode of metastatic infiltration into the brain was presented by
      sqclc. In many cases of the sqclc the end of neoplastic infiltration exceeded the
      area of the examined specimen, represented the material taken during the routine
      neurosurgical procedure (mean distance 153.8 microm compared to group II and
      group III cases: 56.10 and 26.09 microm respectively, p<0.05). The highest
      intensity of astroglial reaction was found around group III tumours (the mean
      number of astrocytes 48.15 SD+/-8.25 per measured area in comparison with 24.76
      SD+/-10.54 and 19.75 SD+/-4.26 around group III and II metastases, respectively
      p<0.05). A remarkable fibrillary gliosis was also found around group III cases
      while the smallest one, comparable with normal nervous tissue glia
      immunoreactivity, within surroundings of group I metastases: group III : II
      p=0.0098, group III : I p=0.0000 and group III : control tissue p=0.0000). There
      were no significant differences in the mean number of vessels within the
      metastatic surroundings. CONCLUSIONS: a dispersed mode of infiltration by sqclc
      metastases to the brain causes precise detection of the macroscopic border
      between the metastatic tumour and the nervous tissue to be much more difficult
      than in sclc, which is sharply demarcated from the surroundings. The poor
      prognosis in sqclc metastases to the brain may, among other, depend on metastatic
      remnants in the form of dispersed neoplastic cells within the seemingly
      uninvolved nervous tissue, not removed during neurosurgical procedures.

PMID- 16565931
TI  - The effect of propofol on astro- and microglial reactivity in the course of
      experimental intracerebral haemorrhage in rats.
AB  - The glial cells play an important role in pathophysiology of the intracerebral
      haemorrhage (ICH). Thus the attempt at evaluating the possible influence of the
      propofol on the reactivity of astro- and microglial cells in the course of ICH
      was performed. 50 rats were divided into two groups depending on the applied
      anaesthesia. All animals were generally anaesthetized with fentanyl,
      dehydrobenzperidol and midazolam. No additional agents were given to the animals
      of the control group (group I). In the experimental group (group II), the animals
      received additionally intraperitoneally propofol in a dose of 50 mg/kg every
      thirty minutes. ICH was produced through infusion of the blood into the striatum.
      The astrocytic and microglial cells population was assessed on the 1, 3, 7, 14
      and 21 days after producing a haematoma using antibodies anti-GFAP and OX42. The
      stereological analysis was applied to estimate the numerical density of
      immunoreactive cells and the distribution of their types. On the 14th and 21st
      days of observation the density of GFAP-immunoreactivity (ir) cells was
      significantly higher in group II than that in group I. There were no differences
      in percentage distribution of GFAP-ir astrocytes between group I and group II. On
      the 3rd, 14th and 21st days of observation the density of OX42-ir cells was
      higher in group II in comparison with group I. For the 7th, and 21st days of
      survival the percentage of the ameboid form of OX42-ir cells was significantly
      lower in group I than that in group II. The administration of propofol during
      anaesthesia in the animals with ICH has evoked an increase of the activation of
      the astro- and microglial cells.

PMID- 16565932
TI  - Interleukin-12 in acute ischemic stroke patients.
AB  - Cytokines are important mediators of stroke-induced immunological/inflammatory
      reaction which contributes to brain infarct progression as well as to the disease
      severity and outcome. The aim of the study was to evaluate the levels of the
      proinflammatory and immunomodulatory cytokine interleukin-12 (IL-12) in serum of
      acute ischemic stroke patients, and to investigate the relation between these
      levels and demographic, laboratory, neuroimaging, and clinical data. The study
      comprised 23 first-ever ischemic stroke patients and 15 age- and sex-matched
      controls. Blood sampling for the determination of IL-12 and such peripheral
      markers of inflammation as erythrocyte sedimentation rate (ESR) and leukocyte
      count, together with cranial CT were performed within 24 h of stroke, while
      neurological and functional deficits were estimated, respectively, with the
      Scandinavian Stroke Scale (SSS) and Barthel Index (BI) within the same period and
      two weeks later. Stroke patients displayed significantly higher serum IL-12
      levels in comparison with controls. The serum IL-12 levels in stroke patients
      correlated significantly with the ESR values, the volume of early brain CT
      hypodense areas, and with the SSS and BI scores calculated within both studied
      times. The results indirectly suggest that IL-12 may play a role in the
      pathophysiology of ischemic stroke.

PMID- 16565933
TI  - Mononuclear subsets in the peripheral blood of multiple sclerosis patients in
      relation to results of brain gadolinium- enhancing imaging.
AB  - Very little is known about processes which are leading to the development of new
      multiple sclerosis (MS) plaques. Therefore, the problem of correlating
      immunological disequilibrium in MS patients with the onset of a relapse and with
      other markers of the disease seems to be of great importance. In our studies we
      have evaluated the mononuclear subsets in the peripheral blood of multiple
      sclerosis patients in relation to results of brain gadolinium-enhancing imaging.
      A positive magnetic resonance imaging (MRI) gadolinium enhancement indicates an
      ongoing inflammation and activity of the MS process, whereas gadolinium (Gd)
      negative imaging should be considered as a sign of stabilization of the MS
      process. MATERIAL AND METHODS: Peripheral blood was taken from 70 MS patients,
      fulfilling the criteria of McDonald et al [8]. Brain MRI was performed using a
      Magneton Impact 1.0 T (Siemens) machine. Enhanced T1 images were obtained after
      administration of 0.1 mmol/kg gadolinium - DTPA. Lymphocyte subsets were analyzed
      by flow cytometry with the aid of specific monoclonal antibodies. RESULTS: The
      relative percentage of the white blood cell count as well as the absolute number
      of mononuclears and of CD3+ lymphocyte were significantly lowered only in the
      group of gadolinium negative MS cases. The CD4+ relative percentage was
      significantly higher both in the total as well as in gadolinium positive and
      negative subgroups. The ratio of CD4/CD8 was significantly higher in MS patients.
      The absolute number of CD4 lymphocytes was the lowest in gadolinium negative MS
      cases. CONCLUSION: An appropriate regulation of the Th /T helper/ cells seems to
      be critical in the control and prevention of diverse states of the disease. In
      the course of an acute process, gadolinium positive imaging as well as
      immunological events, represented by mononuclear subsets in the peripheral blood
      may proceed and change very quickly, whereas gadolinium negative findings
      reflecting a stabilization of processes, are changing more slowly and therefore
      may be detected more easily in peripheral blood cell counts.

PMID- 16565934
TI  - The cerebral form of toxocarosis in a seven-year-old patient.
AB  - INTRODUCTION: Toxocarosis is a consequence of human infection by Toxocara canis
      larvae. There are symptomatic (visceral, ocular) and asymptomatic courses of
      toxocarosis. The cerebral form is very rare. CASE REPORT: We present a seven-year
      old patient who developed a cerebral form of toxocarosis. She demonstrated focal
      neurological symptoms (epilepsy) confirmed by neuro-imaging and histopathological
      examinations. A positive test for toxocarosis essentially completed the other
      outcomes. On the basis of the clinical picture and the conducted tests a
      diagnosis of a cerebral form of toxocarosis was established. Mebendazole was
      applied in treatment.

PMID- 16565935
TI  - Abstracts from the 1st Conference of Polish-German Cooperation Program in
      Neuroscience ordered by the Federal Ministry of Education and Research and the
      Polish Ministry of Education and Science. April 21-22, 2006. Warsaw, Poland.

PMID- 16565936
TI  - [Guidelines for obstetrics and neonatology].

PMID- 16565937
TI  - [Comments on the Guideline: Use of CTG during pregnancy and childbirth].

PMID- 16565939
TI  - [Long-term outcome of preterm neonates: the message behind the statistics].
AB  - In view of the current progress in neonatal intensive care, the present outcome
      of former preterm neonates does not necessarily reflect the future outcome of
      today's preterm neonates. In spite of this statistical uncertainty, long-term
      follow-up studies performed in the past few years point to the fact that the
      sequelae of prematurity may appear well beyond infancy and may be revealed in
      varying manners with increasing age. Therefore, a chronological account of the
      consequences of prematurity is given in this paper, ranging from perinatal
      mortality/morbidity to the problems to be observed during early childhood,
      preschool age, and adolescence right up to the long-term sequelae arising in
      later adulthood. Within this context, a two-fold paradigm shift in neonatology
      becomes apparent in that, first, the outcome of preterm neonates is not a result
      of immaturity per se, yet is significantly influenced by the factors leading to
      preterm birth (inflammation, intrauterine growth restriction), and, second, the
      sequelae of prematurity do not end with the end of neonatal intensive care, but
      are greatly modulated by familial conditions in their further course. Even though
      the statistical data are still subject to changes, these insights form the basis
      of a structured long-term follow-up of preterm neonates which, after the
      progressive establishment of acute treatment strategies, will become an
      increasingly important challenge to neonatology within the framework of
      paediatrics.

PMID- 16565938
TI  - [Use of CTG during pregnancy and childbirth].

PMID- 16565940
TI  - [Quality of data transfer in perinatal data -- experience of a centre].
AB  - BACKGROUND: A sufficient quality of data transfer from written patient records to
      electronic data processing is a precondition for a reasonable usage of perinatal
      data. However the quality of data transfer of the almost 200 characteristics
      routinely recorded at each delivery is largely unknown. MATERIALS AND METHODS:
      The quality of data transfer of 33 characteristics in 350 randomly selected
      singleton deliveries of the women's clinic of the University of Marburg from 2002
      and 2003 has been checked by comparing electronically recorded data with the
      original written documents. RESULTS: The quality of data transfer of the tested
      characteristics turned out to be heterogeneous. Characteristics necessary to
      calculate quality indicators show a very high data quality when excluding the
      characteristic attendance of a paediatrician. The quality of data transfer of
      characteristics denoting time as well as blood gas analysis are heterogeneous.
      Characteristics with a low quality of data transfer are associated with ambiguous
      instructions, the fact that the coding obstetrician is not dealing in the first
      instance with the item being encoded and the characteristics are of no immediate
      relevance for delivery, as well as difficult application of the software.
      CONCLUSION: The quality of data transfer of the characteristics collected in
      perinatal surveys needs to be validated. The type and amount of data being
      collected should be reassessed considering improvements of data quality.

PMID- 16565941
TI  - [Data collection for quality assurance in neonatology: how do physicians compare
      to documentation specialists?].
AB  - BACKGROUND: The quality of data collected for the German nationwide quality
      assurance program in neonatology is currently unknown. The aim of this study was
      to compare the quality of data collected by resident physicians with the quality
      of similar data collected by a dedicated research nurse. METHODS: Data for the
      German national quality assurance program in neonatology, derived from a cohort
      of 128 premature newborns with a birth weight <1500 g and/or a gestational age of
      <30 weeks born in the year 2003, were collected by residents taking care on these
      patients, and separately by a dedicated research nurse for the European Neonatal
      Network (EuroNeoNet). The data set collected for both networks included 44 common
      data items. The two data sets were compared, and any disagreement was double
      checked using the chart of the baby to clarify which of the data entries was
      wrong. Furthermore, as data items are not equally important, a weighted analysis
      of all mistakes was performed. RESULTS: We found wrong data in 108/128 (84 %) of
      the data sets collected by the residents, and in 43/128 (34 %) of the data sets
      collected by the research nurse (p < 0.001). The weighted analysis revealed that
      residents made more mistakes in 30/44 of collected data items, whereas the
      research nurse did worse only in 1/44 data items. CONCLUSION: This study shows
      that the quality of data obtained by our resident physicians was worse than the
      quality of data obtained by our dedicated research nurse.

PMID- 16565942
TI  - The effect of distance to provider on employee response to changes in mental
      health benefits.
AB  - We assess whether distance to provider moderates the effect of a change in mental
      health benefits on treatment initiation of employees of a large US-based company
      for psychiatric disorders. Mental health treatment administrative claims data
      plus eligibility information provided by a Fortune 50 company for the years 1995
      1998 are used for the analysis. The effect of distance is measured using the
      relative effect of the initiative on residents living far from providers compared
      to those living close to providers. We model the probability of treatment
      initiation using a random effects logit specification. We find that the effect of
      distance to provider has the potential to over-shadow other incentives to
      initiate treatment, especially at distances greater than 4 miles. These results
      lend further support to the notion that geographic dispersion of providers should
      be an important consideration when forming a selective contracting network.

PMID- 16565943
TI  - Poly(ether imide) membranes modified with poly(ethylene imine) as potential
      carriers for epidermal substitutes.
AB  - Poly(ether imide) (PEI) membranes were modified with a linear low-molecular
      weight (PETIM_0.6) and a branched high-molecular weight poly(ethylene imine)
      (PETIM_60). The membrane surfaces became more hydrophilic and the zeta potentials
      were shifted from negative to positive zeta values after immobilisation of both
      PETIM. These measurements also indicated the presence of a swollen surface layer
      in the case of PETIM_60, while a regular structuring of the surface was observed
      with scanning force microscopy for PETIM_0.6. A human keratinocyte cell line
      HaCaT was cultured on the different membranes. It was found that HaCaT cell
      growth was stimulated by PETIM_0.6. Cells reached earlier confluence on this
      substratum, while their growth was inhibited on a PEI membrane modified with
      PETIM_60, which makes PEI membranes modified with PETIM_0.6 a promising material
      for in vitro culture of epidermal transplants.

PMID- 16565944
TI  - Investigation of the structure of cellulose in LiCl/DMAc solution and its
      gelation behavior by small-angle X-ray scattering measurements.
AB  - Cellulose gels were prepared from cellulose in lithium chloride/N,N
      dimethylacetamide (LiCl/DMAc) solution. When the cellulose concentration in the
      solution is above the one at which cellulose molecules overlap, cellulose gels
      were formed. While the gel prepared by the addition of water was turbid, the one
      prepared by the ion exchange was colorless, transparent, and optically
      anisotropic. In order to explain this gelation behavior of cellulose, small-angle
      X-ray scattering (SAXS) measurements of the cellulose solutions and the gels were
      performed. The SAXS profiles of the cellulose solutions and the gels suggested
      that the large-scale fluctuation of the molecular chain density in the solution
      can be the origin of the molecular aggregates formed in the gel. Furthermore, the
      differences in the structure of the gels at the macroscopic and the molecular
      level were discussed in terms of the phase separation and the molecular
      association.

PMID- 16565945
TI  - Virtual anatomy: an anatomist's playground.
AB  - Virtual anatomy presents significant advantages over the reality of a cadaver as
      it can provide different views and perspectives, portability, longevity,
      standardization, diversity and most importantly the opportunity to learn the
      anatomy of the living human body instead of the corpse. Virtual anatomy is the
      life-like appearance of visible anatomy, a good example of which is the evolution
      of the Visible Human. Racial and statistical diversity is already developing as
      the population of photographic "Visible Humans" is now at least 10. Virtual
      anatomy should include additional diversity and therefore, consideration should
      be given to the preparation of more visible anatomy that will better support the
      virtual integration of all areas of physiology, kinematics, pathology and
      pathophysiology, development and evolution. Integration of anatomists with
      mathematicians, computer scientists, information scientists, physiologists,
      pathologists and clinicians (and LIST other basic scientist) is needed in order
      to facilitate this development. As this unfolds it is proposed, or challenged,
      that anatomists should maintain their position of responsibility for building
      anatomy as the foundation for all medical and healthcare education. In order to
      maintain that position they must understand and participate in this development
      and enjoy the rewards of teaching more visually empowering, functional, and
      clinical anatomy. The trip is a long one and is only about to begin but the train
      is leaving. Are you on board?

PMID- 16565946
TI  - Biomedical image visualization research using the Visible Human Datasets.
AB  - The practice of medicine and conduct of research in major segments of the
      biologic sciences have always relied on visualizations to study the relationship
      of anatomic structure to biologic function. Traditionally, these visualizations
      have either been direct, via vivisection and postmortem examination, or have
      required extensive mental reconstruction. The revolutionary capabilities of 3-D
      and 4-D medical imaging modalities, together with computer reconstruction and
      rendering of multidimensional medical and histological volume image data, obviate
      the need for physical dissection or abstract assembly. The availability of the
      Visible Human Datasets from the National Library of Medicine, coupled with the
      development of advanced computer algorithms to accurately and rapidly process,
      segment, register, measure, and display high resolution 3-D images, has provided
      a rich opportunity to help advance these important new imaging, visualization,
      and analysis methodologies from scientific theory to clinical practice.

PMID- 16565947
TI  - MR coronary vessel wall imaging: comparison between radial and spiral k-space
      sampling.
AB  - PURPOSE: To compare radial and spiral k-space sampling in navigator-gated ECG
      triggered three-dimensional (3D) coronary vessel wall imaging. MATERIALS AND
      METHODS: The right coronary artery (RCA) vessel walls of eight healthy subjects
      were imaged using a modified double-inversion prepulse in concert with radial and
      spiral data acquisition. For data analysis, two investigators blinded to the
      sequence parameters subjectively assessed image quality in terms of artifacts and
      vessel wall visualization. Objective measures of the signal-to-noise ratio (SNR),
      contrast-to-noise ratio (CNR), and vessel wall definition were also determined.
      RESULTS: Radial k-space sampling demonstrated fewer artifacts and led to improved
      visualization of the coronary vessel wall compared to spiral imaging (P < 0.05).
      This finding was also reflected in a better vessel wall definition using radial
      data acquisition (P < 0.05). SNR and CNR were found to be higher when spiral k
      space sampling was used (n.s.). CONCLUSION: Radial k-space sampling in concert
      with free-breathing navigator-gated cardiac-triggered MRI of the coronary vessel
      wall resulted in fewer motion artifacts and improved vessel wall definition
      compared to spiral k-space sampling. The proposed approach therefore appears to
      be preferable.

PMID- 16565948
TI  - Two approaches to repetition suppression.
AB  - Repetition suppression refers to the phenomenon that prior processing of stimuli
      (or stimulus attributes) decreases activation elicited by processing subsequent
      stimuli with identical attributes. We present two complementary approaches to
      identify regions that show repetition suppression for subsequent sentences with
      either identical: (1) sentence forms or (2) speakers. The first categorical
      approach simply compares sentences that are presented in Same and Different
      blocks. The second factorial approach operationally defines repetition
      suppression as decreased activation for the subsequent Same stimulus relative to
      its preceding sentence. To account for nonspecific time confounds, this approach
      tests for a repetition x condition (Same or Different) interaction. Surprisingly,
      the two approaches revealed different results: Only the categorical analysis
      detected sentence repetition effects in multiple regions within a bilateral
      frontotemporal system that has previously been implicated in sentence processing.
      These discrepancies might be due to the different efficiencies with which the
      particular contrasts were estimated or spurious differences in stimuli or
      attentional set that could not be entirely controlled within a single subject.
      Finally, we combined the two approaches in a [global null] conjunction analysis.

PMID- 16565950
TI  - Proteins of the same fold and unrelated sequences have similar amino acid
      composition.
AB  - It is well established that there is a relationship between the amino acid
      composition of a protein and its structural class (i.e., alpha, beta, alpha +
      beta, or alpha/beta). Several studies have even shown the power of amino acid
      composition in predicting the secondary structure class of a protein. Herein, we
      show that significant similarity in amino acid composition exists not only
      between proteins of the same class, but even between proteins of the same fold.
      To test conjectural explanations for this phenomenon, we analyzed a set of
      structurally similar proteins that are dissimilar in sequence. Based on this
      analysis, we suggest that specific residues that are involved in intramolecular
      interactions may account for this surprising relationship between composition and
      structure.

PMID- 16565949
TI  - Functional segregation of cortical language areas by sentence repetition.
AB  - The functional organization of the perisylvian language network was examined
      using a functional MRI (fMRI) adaptation paradigm with spoken sentences. In
      Experiment 1, a given sentence was presented every 14.4 s and repeated two,
      three, or four times in a row. The study of the temporal properties of the BOLD
      response revealed a temporal gradient along the dorsal-ventral and rostral-caudal
      directions: From Heschl's gyrus, where the fastest responses were recorded,
      responses became increasingly slower toward the posterior part of the superior
      temporal gyrus and toward the temporal poles and the left inferior frontal gyrus,
      where the slowest responses were observed. Repetition induced a decrease in
      amplitude and a speeding up of the BOLD response in the superior temporal sulcus
      (STS), while the most superior temporal regions were not affected. In Experiment
      2, small blocks of six sentences were presented in which either the speaker voice
      or the linguistic content of the sentence, or both, were repeated. Data analyses
      revealed a clear asymmetry: While two clusters in the left superior temporal
      sulcus showed identical repetition suppression whether the sentences were
      produced by the same speaker or different speakers, the homologous right regions
      were sensitive to sentence repetition only when the speaker voice remained
      constant. Thus, hemispheric left regions encode linguistic content while
      homologous right regions encode more details about extralinguistic features like
      speaker voice. The results demonstrate the feasibility of using sentence-level
      adaptation to probe the functional organization of cortical language areas.

PMID- 16565951
TI  - Exploring predictive and reproducible modeling with the single-subject FIAC
      dataset.
AB  - Predictive modeling of functional magnetic resonance imaging (fMRI) has the
      potential to expand the amount of information extracted and to enhance our
      understanding of brain systems by predicting brain states, rather than
      emphasizing the standard spatial mapping. Based on the block datasets of
      Functional Imaging Analysis Contest (FIAC) Subject 3, we demonstrate the
      potential and pitfalls of predictive modeling in fMRI analysis by investigating
      the performance of five models (linear discriminant analysis, logistic
      regression, linear support vector machine, Gaussian naive Bayes, and a variant)
      as a function of preprocessing steps and feature selection methods. We found
      that: (1) independent of the model, temporal detrending and feature selection
      assisted in building a more accurate predictive model; (2) the linear support
      vector machine and logistic regression often performed better than either of the
      Gaussian naive Bayes models in terms of the optimal prediction accuracy; and (3)
      the optimal prediction accuracy obtained in a feature space using principal
      components was typically lower than that obtained in a voxel space, given the
      same model and same preprocessing. We show that due to the existence of artifacts
      from different sources, high prediction accuracy alone does not guarantee that a
      classifier is learning a pattern of brain activity that might be usefully
      visualized, although cross-validation methods do provide fairly unbiased
      estimates of true prediction accuracy. The trade-off between the prediction
      accuracy and the reproducibility of the spatial pattern should be carefully
      considered in predictive modeling of fMRI. We suggest that unless the
      experimental goal is brain-state classification of new scans on well-defined
      spatial features, prediction alone should not be used as an optimization
      procedure in fMRI data analysis.

PMID- 16565952
TI  - HBM functional imaging analysis contest data analysis in wavelet space.
AB  - An analysis of the Functional Imaging Analysis Contest (FIAC) data is presented
      using spatial wavelet processing. This technique allows the image to be filtered
      adaptively according to the data itself, rather than relying on a predetermined
      filter. This adaptive filtering leads to better estimation of the parameters and
      contrasts in terms of mean squared error. It will be shown that by introducing a
      slight bias into the estimation, a large reduction in the variance can be
      achieved, leading to better overall mean squared error estimates. As no single
      filter needs to be preselected, results containing many scales of information can
      be found. In the FIAC data, it is shown that both small-scale and large-scale
      (smoother, more dispersed) effects occur. The combination of small- and large
      scale effects detected in the FIAC data would be easy to miss using conventional
      single filter analysis.

PMID- 16565953
TI  - Applying FSL to the FIAC data: model-based and model-free analysis of voice and
      sentence repetition priming.
AB  - This article presents results obtained from applying various tools from FSL
      (FMRIB Software Library) to data from the repetition priming experiment used for
      the HBM'05 Functional Image Analysis Contest. We present analyses from the model
      based General Linear Model (GLM) tool (FEAT) and from the model-free independent
      component analysis tool (MELODIC). We also discuss the application of tools for
      the correction of image distortions prior to the statistical analysis and the
      utility of recent advances in functional magnetic resonance imaging (FMRI) time
      series modeling and inference such as the use of optimal constrained HRF basis
      function modeling and mixture modeling inference. The combination of hemodynamic
      response function (HRF) and mixture modeling, in particular, revealed that both
      sentence content and speaker voice priming effects occurred bilaterally along the
      length of the superior temporal sulcus (STS). These results suggest that both are
      processed in a single underlying system without any significant asymmetries for
      content vs. voice processing.

PMID- 16565955
TI  - Altered diffusion tensor in multiple sclerosis normal-appearing brain tissue:
      cortical diffusion changes seem related to clinical deterioration.
AB  - PURPOSE: To investigate normal-appearing white (NAWM) and cortical gray (NAGM)
      matter separately in multiple sclerosis (MS) in vivo using diffusion tensor
      imaging (DTI). MATERIALS AND METHODS: In 64 MS patients (12 primary progressive
      [PP], 38 relapsing remitting [RR], 14 secondary progressive [SP]) and 20 healthy
      controls, whole-brain apparent diffusion coefficient (ADC) and fractional
      anisotropy (FA) maps were acquired. A stimulated echo acquisition mode (STEAM)
      DTI sequence was used with minimal geometrical distortion in comparison to echo
      planar imaging (EPI). NAWM and NAGM were identified using conventional magnetic
      resonance (MR) images, allowing a cautious assessment of FA in cortex. RESULTS:
      Histogram analyses showed significant global FA decreases and ADC increases in MS
      NAWM compared to control WM. MS cortical NAGM had no significant global ADC
      increase, but FA was decreased significantly. In regional analyses, nearly all
      NAWM regions-of-interest (ROIs) had significantly increased ADC compared to
      controls, but FA was not changed. In nearly all cortical NAGM ROIs, ADC was
      significantly increased and FA significantly reduced. In multiple linear
      regression analyses in RR/SPMS patients, NAGM-ADC histogram peak height was
      associated more strongly with clinical disability than T2 lesion load.
      CONCLUSION: Tissue damage occurs in both NAWM and cortical NAGM. The cortical
      damage appears to have more clinical impact than T2 lesions.

PMID- 16565954
TI  - Mangafodipir trisodium-enhanced MRI for the detection and characterization of
      focal hepatic lesions: is delayed imaging useful?
AB  - PURPOSE: To investigate the usefulness of early and delayed hepatic MRI after
      mangafodipir trisodium (Mn-DPDP) administration for the detection and
      characterization of focal hepatic lesions. MATERIALS AND METHODS: Forty-five
      patients (31 males and 14 females, mean age = 61 years) with a total of 113
      hepatic lesions (mean size = 3.5 cm) were included in this study (15 with
      hepatocellular carcinoma (HCC, N = 35), 20 with hepatic metastasis (N = 63), five
      with hemangioma (N = 10), three with cholangiocarcinoma (CC, N = 3), and two with
      liver abscess (N = 2)). T1-weighted gradient-echo MR images were obtained before
      and after Mn-DPDP administration, with a mean 18-hour delayed imaging. A
      qualitative analysis (including the size and signal intensity (SI)) and
      quantitative analysis (including enhancement and lesion-liver contrast-to-noise
      ratio (CNR)) were performed on pre- and postcontrast early and delayed MR images.
      RESULTS: Compared to postcontrast early imaging, 17 (48.6%) of 35 HCCs showed
      higher SI, 16 (45.7%) showed no SI change, and two (5.7%) showed lower SI on
      delayed imaging. All 63 metastases, 10 hemangiomas, three CCs, and two abscesses
      showed no SI change. On delayed imaging, ring enhancement was noted in 53
      metastases (84.1%), three hemangiomas (30.0%), and one abscess (50.0%), but was
      not seen in HCCs or CCs. Eight metastases (12.7%) also showed ring enhancement on
      postcontrast early imaging. No newly detected hepatic lesions were revealed on
      postcontrast delayed MR images compared to postcontrast early images. Regarding
      CNR, the HCCs showed a significant increase in CNR from postcontrast early to
      delayed images after administration of Mn-DPDP (P < 0.01). However, none of the
      metastases, hemangiomas, CCs, and abscesses showed a significant increase of CNR
      from postcontrast early to delayed images. CONCLUSION: Postcontrast delayed MR
      images after Mn-DPDP administration were helpful in distinguishing hepatocellular
      from nonhepatocellular lesions, but were not useful for lesion detection and had
      limited utility for lesion characterization, since benign and malignant hepatic
      lesions looked the same.

PMID- 16565956
TI  - Complete response in multiple myeloma: clinical trial E9486, an Eastern
      Cooperative Oncology Group study not involving stem cell transplantation.
AB  - BACKGROUND: The importance of obtaining a complete response (CR) in multiple
      myeloma (MM) treated with chemotherapy is unclear. METHODS: The Eastern
      Cooperative Oncology Group evaluated 653 previously untreated patients with
      active MM randomized to vincristine, carmustine (BCNU), melphalan,
      cyclophosphamide, and prednisone (VBMCP), to VBMCP and recombinant interferon
      alfa-2 (INFalpha-2), or to VBMCP and high-dose cyclophosphamide. RESULTS:
      Objective response was achieved in 420 (67%) of the 628 eligible patients, and 85
      (14%) achieved a CR. Patients receiving VBMCP and recombinant INFalpha-2 had a
      significantly higher CR (18%) than those receiving VBMCP alone (10%) (P = .02).
      The CR rate for VBMCP and high-dose cyclophosphamide was 12%. Median duration of
      survival was 3.5 years for all eligible patients, and the estimated 5-year
      survival rate was 31%. The median duration of survival from the date of objective
      response was 5.1 years for those who achieved a CR and 3.3 years for those with a
      partial response (P < .0001). The median postresponse survival was 6.6 years in
      the 21 patients in CR with nonclonal disease and 4.4 years in the 11 patients in
      CR who had persistent clonal disease. All patients with negative immunofixation
      results and nonclonal plasma cells in whom polymerase chain reaction was
      performed had a positive result (presence of tumor DNA). CONCLUSION: Patients in
      whom a CR was achieved had a longer survival than those who had a partial
      response.

PMID- 16565958
TI  - Factors associated with interval adherence to mammography screening in a
      population-based sample of New Hampshire women.

PMID- 16565959
TI  - ALDH2 genotype-associated differences in the acute effects of alcohol on P300,
      psychomotor performance, and subjective response in healthy young Korean men: a
      double-blind placebo-controlled crossover study.
AB  - BACKGROUND: This study investigated the acute effects of alcohol on
      neurophysiological and psychomotor functions and the subjective response in
      healthy young Korean men according to the mitochondrial aldehyde dehydrogenase
      (ALDH2) genotype. METHOD: A total of 24 males, half with ALDH2*1/*1 (active form)
      and the rest with ALDH2*1/*2 (inactive form), were selected through genotyping.
      In a double-blind placebo-controlled crossover design, each subject consumed
      either a 0.5 g/kg dose of alcohol or a placebo on two separate occasions, 1 week
      apart. The blood alcohol concentrations (BACs), P300 of event-related potential,
      psychomotor performance, and perceived feelings were assessed. RESULTS: Although
      the BACs were similar between the two groups, the effects of alcohol on P300 were
      greater overall in subjects with ALDH2*1/*2 than in subjects with ALDH2*1/*1.
      Psychomotor performance was more impaired after alcohol ingestion in subjects
      with ALDH2*1/*2 than in subjects with ALDH2*1/*1. The subjective response after
      alcohol ingestion was more negative in subjects with ALDH2*1/*2, compared to
      subjects with ALDH2*1/*1. CONCLUSIONS: These results suggest that the ALDH2
      polymorphism is an important factor in determining the effects of alcohol on
      various psychobehavioral functions.

PMID- 16565960
TI  - Effects of CD44 antibody-- or RGDS peptide--immobilized magnetic beads on cell
      proliferation and chondrogenesis of mesenchymal stem cells.
AB  - We evaluated the efficacy of a novel mesenchymal stem cell (MSC) delivery system
      using an external magnetic field for cartilage repair in vitro. MSCs were
      isolated from the bone marrow of Sprague Drawley rats and expanded in a
      monolayer. To use the MSC delivery system, two types of MSC-magnetic bead
      complexes were designed and compared. Expanded MSCs were combined with small
      sized (diameter: 310 nm) carboxyl group-combined (0.01-0.04 micromol/mg) magnetic
      beads, Ferri Sphere 100C, through either anti-rat CD44 mouse monoclonal
      antibodies or a synthetic cell adhesion factor, arginine (R)-glycine (G)-aspartic
      acid (D)-serine (S) (RGDS) peptide. Both cell complexes were successfully
      created, and were able to proliferate in monolayer culture up to at least day 7
      after separation of magnetic beads from the cell surface, although the
      proliferation of the complexes was slower in the early period of culture than
      that of non-labeled rat MSCs (after 7 days of culture: proliferation of CD44
      antibody-bead complexes, approximately 50%; RGDS peptide-bead complexes, 70%
      versus non-labeled rat MSCs, respectively). These complexes were seeded onto
      culture plates with or without an external magnetic force (magnetic flux density
      was 0.20 Tesla at a distance of 2 mm from plate base) generated by a neodymium
      magnet, and supplemented with chondrogenic differentiation medium. Both complexes
      could be attached and gathered effectively under the influence of the external
      magnet, and CD44-bead complexes could effectively generate chondrogenic matrix in
      monolayer culture. In a three-dimensional culture system, the production of a
      dense chondrogenic matrix and the expression of type II collagen and aggrecan
      mRNA were detected in both complexes, and the chondrogenic potential of these
      complexes was only a little less than that of rat MSCs alone. Thus, we conclude
      that due to the fact that MSC-RGDS peptide-bead complexes are composed using a
      biodegradable material, RGDS peptide, as a mediator, the RGDS peptide-bead
      complex is more useful for minimally invasive clinical applications using our
      design of magnetic MSC delivery system than CD44 antibody-beads.

PMID- 16565961
TI  - The optimal SAM surface functional group for producing a biomimetic HA coating on
      Ti.
AB  - Commercial interest is growing in biomimetic methods that employ self assembled
      mono-layers (SAMs) to produce biocompatible HA coatings on Ti-based orthopedic
      implants. Recently, separate studies have considered HA formation for various SAM
      surface functional groups. However, these have often neglected to verify
      crystallinity of the HA coating, which is essential for optimal bioactivity.
      Furthermore, differing experimental and analytical methods make performance
      comparisons difficult. This article investigates and evaluates HA formation for
      four of the most promising surface functional groups: --OH, --SO(3)H, --PO(4)H(2)
      and --COOH. All of them successfully formed a HA coating at Ca/P ratios between
      1.49 and 1.62. However, only the --SO(3)H and --COOH end groups produced a
      predominantly crystalline HA. Furthermore, the --COOH end group yielded the
      thickest layer and possessed crystalline characteristics very similar to that of
      the human bone. The --COOH end group appears to provide the optimal SAM surface
      interface for nucleation and growth of biomimetic crystalline HA. Intriguingly,
      this finding may lend support to explanations elsewhere of why human bone
      sialoprotein is such a potent nucleator of HA and is attributed to the protein's
      glutamic acid-rich sequences.

PMID- 16565962
TI  - The paraventricular nucleus of the thalamus as an interface between the orexin
      and CART peptides and the shell of the nucleus accumbens.
AB  - The paraventricular nucleus of the thalamus (PVT) receives afferents from the
      brainstem and has been thought to relay arousal related information to specific
      limbic forebrain areas, including the nucleus accumbens. More recent anatomical
      observations suggest that the PVT also receives afferents from various
      hypothalamic nuclei. The present anatomical experiments investigated the
      innervation of the PVT by fibers immunoreactive for orexin and cocaine and
      amphetamine related transcript (CART), two feeding-related peptides highly
      concentrated in the hypothalamus. Emphasis was placed on identifying the
      relationship between these neuropeptides and PVT neurons projecting to the shell
      of the nucleus accumbens (NacSh). Infusion of a retrograde tracer into the NacSh
      labeled numerous cells of the midline and intralaminar thalamus, most of which
      were restricted to the PVT. The retrograde tracer, orexin fibers, and CART fibers
      were immunopositive throughout the entire PVT whereas no overlap between signals
      was evident within adjacent thalamic regions. High-magnification light and
      confocal microscopy showed that both orexin and CART fibers made frequent contact
      with retrogradely labeled neurons throughout the anteroposterior PVT.
      Furthermore, single PVT cells retrogradely labeled from the NacSh were apposed by
      both orexin and CART fibers. The present experiments provide the first evidence
      suggesting a role for the PVT as a relay of hypothalamic activity to the nucleus
      accumbens. The PVT may function to link visceral arousal signals with limbic
      regions involved in behavioral responses.

PMID- 16565964
TI  - Inhibition of [11C]mirtazapine binding by alpha2-adrenoceptor antagonists studied
      by positron emission tomography in living porcine brain.
AB  - We have developed [(11)C]mirtazapine as a ligand for PET studies of
      antidepressant binding in living brain. However, previous studies have determined
      neither optimal methods for quantification of [(11)C]mirtazapine binding nor the
      pharmacological identity of this binding. To obtain that information, we have now
      mapped the distribution volume (V(d)) of [(11)C]mirtazapine relative to the
      arterial input in the brain of three pigs, in a baseline condition and after
      pretreatment with excess cold mirtazapine (3 mg/kg). Baseline V(d) ranged from 6
      ml/ml in cerebellum to 18 ml/ml in frontal cortex, with some evidence for a small
      self-displaceable binding component in the cerebellum. Regional binding
      potentials (pBs) obtained by a constrained two-compartment model, using the V(d)
      observation in cerebellum, were consistently higher than pBs obtained by other
      arterial input or reference tissue methods. We found that adequate quantification
      of pB was obtained using the simplified reference tissue method. Concomitant PET
      studies with [(15)O]-water indicated that mirtazapine challenge increased CBF
      uniformly in cerebellum and other brain regions, supporting the use of this
      reference tissue for calculation of [(11)C]mirtazapine pB. Displacement by
      mirtazapine was complete in the cerebral cortex, but only 50% in diencephalon,
      suggesting the presence of multiple binding sites of differing affinities in that
      tissue. Competition studies with yohimbine and RX 821002 showed decreases in
      [(11)C]mirtazapine pB throughout the forebrain; use of the multireceptor version
      of the Michaelis-Menten equation indicated that 42% of [(11)C]mirtazapine binding
      in cortical regions is displaceable by yohimbine. Thus, PET studies confirm that
      [(11)C]mirtazapine affects alpha(2)-adrenoceptor binding sites in living brain.

PMID- 16565963
TI  - Facilitation of glutamate release by nicotine involves the activation of a
      Ca2+/calmodulin signaling pathway in rat prefrontal cortex nerve terminals.
AB  - The effect of nicotine on evoked glutamate release from isolated nerve terminals
      (synaptosomes) from rat prefrontal cortex was examined. We found that nicotine
      significantly potentiated 4-aminopyridine (4AP)-evoked glutamate release, and
      this potentiatory effect was mimicked by the selective alpha7 nicotinic receptor
      agonist choline and was blocked by the selective alpha7 nicotinic receptor
      antagonist methyllycaconitine, indicating its mediation by alpha7 nicotinic
      receptors. Examination of the effect of nicotine on cytosolic [Ca(2+)] revealed
      that the potentiation of glutamate release was associated with an increase in
      voltage-dependent Ca(2+) influx through N- and P/Q-type Ca(2+) channels. The
      potentiatory effect of nicotine on Ca(2+) influx seems to be attributed to its
      increasing synaptosomal excitability because nicotine significantly increased
      depolarization-evoked increase in the intrasynaptosomal free Na(+) concentration
      and 4AP-evoked depolarization of the synaptosomal plasma membrane potential.
      Also, Ca(2+) ionophore ionomycin-induced glutamate release was enhanced by
      nicotine, and this action was blocked by methyllycaconitine. These results
      suggest that nicotine exerts its potentiatory effect presynaptically, likely
      through the activation of alpha7 nicotinic receptors, resulting in Na(+) influx
      and local depolarization, which subsequently enhances the Ca(K+) entry through
      voltage-dependent N-and P/Q-type Ca(2+) channels as well as the vesicular release
      machinery to cause an increase in evoked glutamate release from rat
      prefrontocortical nerve terminals. Moreover, in this release potentiation may
      involve an activation of Ca(2+)/calmodulin signaling pathway as nicotine-mediated
      potentiation of 4AP- and ionomycin-evoked glutamate release were significantly
      attenuated by KN62, a selective inhibitor of Ca(2+)/calmodulin-dependent kinase
      II.

PMID- 16565965
TI  - Regional alterations in RGS4 protein in schizophrenia.
AB  - The regulator of G protein signaling (RGS) molecules are a class of proteins that
      modulate the signaling activity of G-protein coupled receptors. Regulator of G
      protein signaling 4 (RGS4) is of particular interest in schizophrenia since it is
      associated with the dopamine (DA) receptor, its expression is altered in affected
      CNS tissue, and polymorphisms in the RGS4 gene are being examined as risk factors
      for the disease (Morris et al.2004, Am J Med Genet B Neuropsychiatr Genet 125:50
      53; Prasad et al.2005, Mol Psychiatry 10:213-219; Williams et al.2004, Biol
      Psychiatry 55:192-195). To further test for the involvement of RGS4 expression in
      schizophrenia, we examined a selection of different cortical and subcortical
      regions in human brain for alterations in RGS4 mRNA and protein expression. To
      evaluate the effect of antipsychotic medication on RGS4 expression levels, we
      compared a subset of treated and untreated cases that were off antipsychotic
      medication for at least 3 months prior to death. We report a significant decrease
      in RGS4 mRNA levels in the cingulate gyrus, superior frontal gyrus, and the
      insular cortex of all schizophrenia cases when compared with controls. A decrease
      in RGS4 mRNA was also observed in the caudate, but only in the medicated
      schizophrenia cases. Measurement of protein levels using Western blot
      demonstrated that RGS4 protein is decreased in the frontal cortex of
      schizophrenia cases.

PMID- 16565966
TI  - The acute and chronic administration of the 5-HT(2B/2C) receptor antagonist SB
      200646A significantly alters the activity of spontaneously active midbrain
      dopamine neurons in the rat: An in vivo extracellular single cell study.
AB  - This study examined the effect of the acute and chronic administration of the 5
      HT(2B/2C) receptor antagonist N-(1-methyl-5-indolyl)-N'-(3-pyridyl) urea
      hydrochloride (SB-200646A) on the activity of spontaneously active DA cells in
      the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in
      anesthetized, male Sprague-Dawley rats. This was accomplished using in vivo
      extracellular single cell recording. The i.v. administration of 4-16 mg/kg of SB
      200646A significantly increased the firing rate and % events as bursts in
      spontaneously active VTA DA neurons and significantly increased the % events as
      burst in SNC DA neurons. The acute i.p. administration of 20 and 40 mg/kg of SB
      200646A significantly increased the number of spontaneously active VTA DA neurons
      when compared with vehicle-treated controls. The acute administration of 10 mg/kg
      of SB-200646A significantly increased the coefficient of variation in
      spontaneously active SNC and DA neurons when compared with vehicle-treated
      controls. However, the acute i.p. administration of 20 mg/kg of SB-200646A
      significantly decreased the degree of bursting of VTA DA neurons. Similary,
      chronic i.p. administration of 10 mg/kg of SB-200646 did not significantly alter
      firing, whereas chronic administration of 20 mg/kg of SB-200646A or 20 mg/kg of
      clozapine significantly decreased the number of spontaneously active VTA DA
      neurons when compared with vehicle-treated controls. The SB-200646A-induced
      decrease in the number of spontaneously active VTA DA neurons was reversed by the
      i.v. administration of (+)-apomorphine or (-)-baclofen. The chronic i.p.
      administration of either 10 or 20 mg/kg of SB-200646A did not significantly alter
      the firing pattern of spontaneously active SNC DA neurons. However, the chronic
      administration of 20 mg/kg of SB-200646A significantly increased the degree of
      bursting in VTA DA neurons when compared with vehicle. Overall, the acute and
      chronic administration of SB-200646A produces in vivo electrophysiological
      effects, resembling that of atypical antipsychotic drugs.

PMID- 16565967
TI  - Distribution of constitutively expressed MEF-2A in adult rat and human nervous
      systems.
AB  - Myocyte enhancer factor 2A (MEF-2A) is a calcium-regulated transcription factor
      that promotes cell survival during nervous system development. To define and
      further characterize the distribution pattern of MEF-2A in the adult mammalian
      brain, we used a specific polyclonal antiserum against human MEF-2A to identify
      nuclear-localized MEF-2A protein in hippocampal and frontal cortical regions.
      Western blot and immunocytochemical analyses showed that MEF-2A was expressed not
      only in laminar structures but also in blood vessels of rat and human brains. MEF
      2A was colocalized with doublecortin (DCX), a microtubule-associated protein
      expressed by migrating neuroblasts, in CA1 and CA2 boundaries of the hippocampus.
      MEF-2A was expressed heterogeneously in additional structures of the rat brain,
      including the striatum, thalamus, and cerebellum. Furthermore, we found a strong
      nuclear and diffuse MEF-2A labeling pattern in spinal cord cells of rat and human
      material. Finally, the neurovasculature of adult rats and humans not only showed
      a strong expression of MEF-2A but also labeled positive for hyperpolarization
      activated, cyclic nucleotide-regulated (HCN) channels. This study further
      characterizes the distribution pattern of MEF-2A in the mammalian nervous system,
      demonstrates that MEF-2A colocalizes with DCX in selected neurons, and finds MEF
      2A and HCN1 proteins in the neurovasculature network.

PMID- 16565968
TI  - Central venous catheter and Stenotrophomonas maltophilia bacteremia in cancer
      patients.
AB  - BACKGROUND: Stenotrophomonas maltophilia bacteremia is frequently found in cancer
      patients. This study attempted to determine how often the catheters were the
      source of this infection and the risk factors associated with catheter-related
      bacteremias. METHODS: The microbiology records were retrospectively reviewed of
      all cancer patients having S. maltophilia bacteremia and indwelling central
      venous catheters seen between January 1998 and January 2004. In a multivariate
      analysis the patients' clinical characteristics, antimicrobial therapy, outcome,
      and source of bacteremia that were significantly associated with definite
      catheter-related S. maltophilia bacteremia as opposed to secondary bacteremia
      were identified. RESULTS: A total of 217 bacteremias were identified in 207
      patients: 159 (73%) were primary catheter-related (53 definite, 89 probable, and
      17 possible), 11 (5%) were primary noncatheter-related, and 47 (22%) were
      secondary. Multivariate analysis showed the following factors to be independently
      associated with definite catheter-related bacteremias: 1) polymicrobial
      bacteremia (odds ratio [OR], 7.6; 95% confidence interval [95% CI], 1.3-45.5); 2)
      no prior intensive care unit admission (OR, 0.06; 95% CI, 0.005-0.578); and 3)
      nonneutropenic status at onset (OR, 0.07; 95% CI, 0.013-0.419). The response rate
      to appropriate antibiotics and catheter removal was 95% in the patients with
      definite catheter-related bloodstream infections, compared with only 56% in the
      patients with secondary bacteremias (P = .001). CONCLUSIONS: The majority of the
      S. maltophilia bacteremias occurring in cancer patients with indwelling central
      venous catheters appear to be catheter-related and are often polymicrobial.
      Catheter-related S. maltophilia bacteremias occurred more frequently in
      noncritically ill, nonneutropenic patients, and prompt removal of the catheter
      was found to be associated with a better prognosis.

PMID- 16565969
TI  - Class distinction between follicular adenomas and follicular carcinomas of the
      thyroid gland on the basis of their signature expression.
AB  - BACKGROUND: Nodules of the thyroid gland are observed frequently in patients who
      undergo ultrasound studies. The majority of these nodules are benign,
      corresponding to goiters or adenomas, and only a small fraction corresponds to
      carcinomas. Among thyroid tumors, the diagnosis of follicular adenocarcinomas by
      preoperative fine-needle aspiration biopsy is a major challenge, because it
      requires inspection of the entire capsule to differentiate it from adenoma.
      Consequently, large numbers of patients undergo unnecessary thyroidectomy.
      METHODS: Using data from gene expression analysis, the authors applied Fisher
      linear discriminant analysis and searched for expression signatures of individual
      samples of adenomas and follicular carcinomas that could be used as molecular
      classifiers for the precise classification of malignant and nonmalignant lesions.
      RESULTS: Fourteen trios of genes were described that fulfilled the criteria for
      the correct classification of 100% of samples. The robustness of these trios was
      verified by using leave-1-out cross-validation and bootstrap analyses. The
      results demonstrated that, by combining trios, better classifiers could be
      generated that correctly classified >92% of samples. CONCLUSIONS: The strategy of
      classifiers based on individual signatures was a useful strategy for
      distinguishing between samples with very similar expression profiles.

PMID- 16565970
TI  - Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha
      for advanced hepatocellular carcinoma with portal venous invasion.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) with portal venous invasion (PVI) has
      a very poor prognosis, with a median survival of 3 months and virtually no
      survival at 1 year. The combination of intraarterial 5-fluorouracil (FU) and
      systemic interferon-alpha (IFNalpha) was recently reported to be effective
      against HCC with PVI, but these were small pilot studies. METHODS: One hundred
      and sixteen patients with HCC with PVI received IFNalpha (5,000,000 U
      intramuscularly on Days 1, 3, and 5 of each week of treatment) and 5-FU (500 mg
      into hepatic artery on Days 1-5 of the first and second week of each 4-week
      cycle). The therapy was either terminated at the end of the first cycle in cases
      with progressive disease, or continued for at least 3 cycles, when responses to
      treatment were evaluated by Eastern Cooperative Oncology Group criteria. The
      survival rate was compared with that of historical controls (n = 40). RESULTS:
      Nineteen (16%) patients showed complete response and another 42 (36%) showed
      partial response. Adverse events were limited to nausea and appetite loss. The
      survival rates at 12 and 24 months among overall patients were 34% and 18%,
      respectively, in contrast to 15% and 5% among the historical controls. Survival
      rates at 12 and 24 months were 81% and 59% among complete responders,
      respectively, and 43% and 18% among partial responders. CONCLUSION: The
      combination therapy with 5-FU and IFN was safe, and substantially improved the
      survival rate among the complete responders. These results provide a rationale
      for future randomized controlled trials.

PMID- 16565972
TI  - Differential expression of VEGF-A and angiopoietins in cartilage tumors and
      regulation by interleukin-1beta.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF)-A and angiopoietin (Ang)-1
      and Ang-2 are key factors in angiogenic signaling. In this study the expression
      of these factors was identified in cartilage tumors. As interleukin (IL)-1beta
      has been found to be an indispensable factor in angiogenic signaling, we further
      analyzed the effect of IL-1beta on the expression of VEGF-A, Ang-1, and Ang-2
      using a previously established cell culture model. METHODS: Surgical specimens of
      enchondromas, conventional chondrosarcomas, and dedifferentiated chondrosarcomas
      were obtained from 72 patients. VEGF-A, Ang-1, and Ang-2 mRNA expression was
      detected by conventional and quantitative reverse transcription polymerase chain
      reaction (PCR). VEGF-A expression was also detected by immunohistochemistry or
      Western blot. RESULTS: Differential expression of VEGF-A, Ang-1, and Ang-2 was
      clearly demonstrated in cartilage tumors. VEGF-A expression was positively
      correlated with the tumor type. Higher VEGF-A expression levels were detected in
      conventional chondrosarcomas Grades II and III (using a 3-tier grading system)
      than in dedifferentiated chondrosarcomas (P < .05). A typical pattern of VEGF-A
      isoforms was identified, including VEGF(121), VEGF(145), VEGF(165), and
      VEGF(189). Ang-1 presented as a low-level transcript with slightly elevated
      levels in chondrosarcomas (P < .05). Highly variable Ang-2 expression levels were
      detected in solitary cases of conventional chondrosarcomas. IL-1beta regulated
      VEGF-A and Ang-1 expressions in a dose-dependent manner. Whereas low IL-1beta
      concentrations increased VEGF-A and Ang-1 transcription, high IL-1beta
      concentrations had the opposite effect. IL-1beta did not activate Ang-2
      expression. CONCLUSIONS: Angiogenic signaling in cartilage tumors is variable and
      at least partly regulable by IL-1beta. The findings are of therapeutic relevance,
      either as a desired effect or a side effect in medical treatment.

PMID- 16565971
TI  - Multicenter Phase II trial of high-dose imatinib mesylate in metastatic melanoma:
      significant toxicity with no clinical efficacy.
AB  - BACKGROUND: Systemic treatment of metastatic melanoma is largely ineffective and
      alternative approaches are needed. Imatinib mesylate is an oral tyrosine kinase
      inhibitor that targets bcr-Abl, c-kit, platelet-derived growth factor receptor
      (PDGFR)-alpha, and PDGFR-beta, leading to remarkable clinical responses in
      several cancers. Signal transduction via c-kit, PDGFR-alpha, and PDGFR-beta has
      been demonstrated in malignant melanoma. METHODS: The primary objective of this
      Phase II study was to determine the response rate, response duration, and the
      frequency of 6-month progression-free survival in patients who could receive up
      to 2 prior therapeutic regimens. Initially, patients received imatinib at at dose
      of 400 mg twice orally each day. Based on Simon's optimal design, the study
      allowed entry of 21 patients; if there were > or = 2 objective responses, accrual
      would then continue to a total of 41 patients. RESULTS: Twenty-six patients were
      enrolled. Patients experienced 29 episodes of Grade 3 and 2 episodes of Grade 4
      toxicity (according to National Cancer Institute common toxicity criteria). No
      objective clinical responses were noted among the 25 evaluable patients. The
      median time to progression was 54 days and the median overall survival was 200
      days. No patient was free of disease progression at 6 months. Paraffin-embedded
      tumor specimens from 15 patients were tested for expression of imatinib
      responsive kinases by immunohistochemistry. Three tumors had moderate and 5
      tumors had weak staining for c-kit. Five tumor samples had weak staining for
      PDGFR-alpha and -beta. CONCLUSIONS: Imatinib is an inactive single agent in
      metastatic melanoma in a population of predominantely pretreated patients. The
      levels of c-kit and/or PDGFR-alpha, -beta expression in the current study were
      lower than previously reported. Alternative treatment strategies remain a
      priority for patients with advanced melanoma.

PMID- 16565974
TI  - Relation between rotation in the 6-OHDA lesioned rat and dopamine loss in
      striatal and substantia nigra subregions.
AB  - The relation between the rotation response to drug-induced activation of the
      dopamine (DA) receptor in the rat unilaterally lesioned with 6-hydroxydopamine (6
      OHDA) in the substantia nigra (SN) and the loss of DA in subregions of the SN and
      caudate-putamen (C/PUT) is not clear. Here this relation was examined in 23 rats
      classified as rotators to amphetamine (5 mg/kg). After their response was
      characterized in terms of ipsilateral rotation, contralateral rotation, and oral
      stereotypy in one place, they were divided into high, medium, low, and very low
      rotators. The loss of DA in each group was visualized on brain sections
      immunoreacted to tyrosine hydroxylase (TH). The density of the TH label on the
      side of the lesion was compared to that on the intact side. In the ventral
      midbrain, the density was determined in the SN subdivided into far lateral,
      lateral, central, and medial subregions and also in the ventral tegmental area
      (VTA). In the forebrain, it was determined in the C/PUT subdivided into lateral,
      central, and medial subregions and also in the nucleus accumbens (ACC). These
      measurements led to three principal findings. The first was a positive overall
      correlation between rotation and loss of TH label. The second was a correlation
      between rotation and penetration of the loss from the lateral subregions into
      more medial areas. The third was a larger loss in SN and VTA (midbrain) than in
      C/PUT and ACC (forebrain). These findings show that rotation depended not only on
      the overall loss of DA but also on its distribution across subregions. The loss
      in the lateral subregion, always the largest regardless of the rate of rotation,
      may have been the first step in inducing the motor abnormality, and the loss in
      the central and medial subregions may have served to enhance the abnormality due
      to the loss in the lateral subregion.

PMID- 16565973
TI  - Validation studies on the 5-hydroxy-L-[beta-11C]-tryptophan/PET method for
      probing the decarboxylase step in serotonin synthesis.
AB  - The two-tissue compartment model, including irreversible trapping in the second
      compartment (2TCM) is used to describe the kinetics of 5-Hydroxy-L-[beta-(11)C]
      tryptophan ([(11)C]HTP), a radioligand used in positron emission tomography (PET)
      for probing the second enzymatic step in the biosynthesis of serotonin. In this
      study, we examined the capacity of the model to track pharmacological changes in
      this biological process. We also investigated the potential loss of [(11)C]HTP
      derived radioactivity during a PET study, since loss should be negligible not to
      alter quantification. Six rhesus monkeys were investigated using bolus
      [(11)C]HTP/PET methodology before and after pharmacological intervention. The
      second enzymatic step in serotonin synthesis was inhibited using the aromatic L
      amino acid decarboxylase inhibitor NSD1015 (10 mg/kg). The extent of [(11)C]
      derived radioactivity loss from the brain was studied by inhibition of the enzyme
      responsible for formation of the tissue metabolite, monoamine oxidase A, using
      clorgyline (2 mg/kg). After NSD1015, the uptake of [(11)C]HTP-derived
      radioactivity was increased in all the investigated brain regions, while the
      parameter used to reflect decarboxylase activity, the net accumulation rate
      constant (K(acc)), was decreased by 37% in the striatum, compared with baseline.
      Pretreatment with clorgyline did not change the brain uptake of [(11)C]HTP
      derived radioactivity or K(acc). This study demonstrates that the 2TCM for
      [(11)C]HTP/PET is able to detect changes occurring during alteration of the
      biological process (i.e., the conversion of HTP to serotonin). Elimination of the
      radiotracer metabolite [(11)C]HIAA from the brain may be considered negligible if
      the PET study is limited to 60 min.

PMID- 16565976
TI  - Drug abuse in women with eating disorders.
AB  - OBJECTIVE: Drug abuse in women with eating disorders has received relatively
      little attention. The frequency of drug use disorder (DUD) by specific drug type
      was examined in the current longitudinal study. METHOD: In a prospective study,
      women diagnosed with either anorexia nervosa (AN; n = 136) or bulimia nervosa
      (BN; n = 110), were interviewed and assessed for research diagnostic criteria
      (RDC) DUD every 6-12 months over 8.6 years. RESULTS: Forty-two (17%) women in the
      current longitudinal study had a lifetime history of DUD, with 19 prospective
      onsets over the course of the study (9 AN and 10 BN). The most commonly abused
      illicit drugs were amphetamines, cocaine, and marijuana, and rates of DUD did not
      differ between intake diagnoses of AN and BN. CONCLUSION: Drug abuse in women
      with eating disorders is an area of clinical concern and should be monitored
      routinely throughout the treatment process.

PMID- 16565977
TI  - Polymorphism and pseudopolymorphism of salicaine and salicaine hydrochloride
      crystal polymorphism of local anaesthetic drugs, part V.
AB  - The local anaesthetic drug salicaine hydrochloride (hydroxytetracaine
      hydrochloride, 4-butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester
      hydrochloride, SLCHC) and the free-base salicaine (SLC) were characterized by
      thermal analysis, vibrational and solid-state NMR-spectroscopy, X-ray powder
      diffraction, X-ray single crystal structure analysis, and water vapor sorption
      analysis. Additionally, the crystal structures of the anhydrate mod. II degrees
      (monoclinic, space group P2(1)/n), the hydrated mod. I (triclinic, space group
      P(bar)1), and of the free base (SLC) in the form of the hemihydrate (triclinic,
      space group P(bar)1 are discussed. Mod. II degrees of the polymorphic SLCHC is
      the thermodynamically stable form at room temperature and is present in
      commercial products mostly contaminated with a hydrated form that is isomorphic
      with mod. I. Mod. II degrees crystallizes from most organic solvents and from the
      melt below 110 degrees C. Mod. I crystallizes from the melt at temperatures above
      110 degrees C, and additionally appears on dehydration of the hydrated mod. I. A
      third polymorph monotropically related to mod. II degrees was found by freeze
      drying. The free-base SLC was found to crystallize from ethanol/water as a
      triclinic hemihydrate.

PMID- 16565975
TI  - Detection and characterization of variant and modified structures of proteins in
      blood and tissues by mass spectrometry.
AB  - Some variant proteins cause diseases, and some diseases result in increases of
      proteins with abnormally modified structures. The detection, characterization,
      and estimation of the relative amounts of protein variants and abnormally
      modified proteins are important for clinical diagnosis and for elucidation of the
      mechanisms of the pathogenesis of diseases. Analysis of the covalent structures
      of proteins using matrix-assisted laser desorption time-of-flight mass
      spectrometry (MALDI-TOF-MS) and liquid chromatography-electrospray ionization MS
      (LC-ESI-MS), which had been developed by the early 1990s, have largely replaced
      analyses by conventional protein chemistry. Here, we review the detection and
      characterization of hemoglobin variants, HbA1c measurement, detection of
      carbohydrate-deficient transferrin, and identification of variants of
      transthyretin (TTR) and Cu/Zn-superoxide dismutase (SOD-1) using soft ionization
      MS. We also propose the diagnostic application of the signals of modified forms
      of TTR, that is, S-sulfonated TTR and S-homocysteinyl TTR. The relative peak
      height ratio of the abnormal/normal components gives valuable information about
      the instability of variants and enables the detection of unstable Hb subunits or
      thalassemia heterozygotes. We found unique modified structures of TTR that
      suggested changes in amyloid fibrils.

PMID- 16565978
TI  - Self-assembled polyelectrolyte nanocomplexes between chitosan derivatives and
      insulin.
AB  - Polyelectrolyte complexes (PEC) formed from chitosan derivatives and insulin was
      prepared and parameters influencing complex formation were characterized.
      Turbidimetric titration, in combination with dynamic light scattering (DLS) and
      laser doppler anemometry (LDA), were used to study the complexation process. The
      morphology of the PECs was determined using atomic force microscopy (AFM). PEC
      formation was predominantly pH-dependent. Complexation with insulin occurred only
      above critical pH value (pHc) of 6.0 for all the chitosan derivatives
      investigated. Soluble PECs in the size range of 200-500 nm with spherical or
      subspherical morphology and smooth surface structure were obtained at optimized
      polymer/insulin charge ratios. Optimal conditions were obtained when the pH of
      PECs was in the range of 6.5-8.0, depending on polymer structure. The stability
      of PECs was influenced by polymer chain length. Only when the MW of the polymers
      was > or =25-kDa PEC precipitation could be avoided. An increase in the ionic
      strength of the medium accelerated complex dissociation. Chitosan methylation and
      PEGylation significantly improved the stability of insulin in the PECs. Moreover,
      the PEC could protect insulin from degradation even at 50 degrees C for at least
      6 h. All complexes could be lyophilized without influencing the particle size,
      complex concentration, and stability of insulin. On the basis of our results, we
      suggest that interactions involved in PEC formation were predominantly
      electrostatic in nature, involving the positively charged amino groups of
      chitosan and the negatively charged insulin above its isoelectric point.
      Intranasal absorption of the polyelectrolyte nanocomplexes will be studied in
      vivo.

PMID- 16565979
TI  - A risk-based approach to establish stability testing conditions for tropical
      countries.
AB  - The external stability risk factors heat and moisture are evaluated with respect
      to the development of pharmaceutical products intended to be marketed in tropical
      and subtropical countries. The mean daily temperatures and dewpoints measured
      four times per day at selected places in Southeast Asia, South America, China,
      Southern Africa and the Caribbean are used to calculate the daily and monthly
      fluctuations of temperature and partial water vapour pressure, the mean kinetic
      temperature and the relative humidity. Based on these data, the hottest and the
      most humid place in each country or region are identified to reflect the worst
      case for the specific region. A formula to calculate safety margins for
      temperature and partial vapour pressure is introduced taking into consideration
      the difference between measured meteorological parameters and the stability
      testing conditions. An appropriate long-term stability testing condition is
      proposed for each selected country, related to the worst case for each specific
      region and the safety margins, as well as its classification in either Climatic
      Zone IVA or IVB.

PMID- 16565980
TI  - Ductus venosus shunting in the fetal venous circulation: regulatory mechanisms,
      diagnostic methods and medical importance.
AB  - The fetal liver is located at the crossroads of the umbilical venous circulation.
      Anatomically, the ductus venosus (DV) and the intrahepatic branches of the portal
      vein are arranged in parallel. The actual DV shunting rate, i.e. the percentage
      of umbilical blood flow entering the DV measured by Doppler velocimetry, seems to
      be lower than that estimated using radioactively-labeled microspheres. In human
      fetuses the DV shunting rate is about 20-30%. Increases in the DV shunting rate
      are a general adaptational mechanism to fetal distress. Hypoxia results in a
      significant increase in the DV shunting rate, most probably in order to ensure an
      adequate supply of oxygen and glucose to vitally important organs such as the
      brain and heart. The mechanism of blood flow redistribution between the fetal
      liver and the DV is still a matter of debate. The isthmic portion of the DV
      contains less smooth muscle tissue than the intrahepatic branches of the portal
      vein, which in vitro react more forcefully in response to catecholamines than the
      DV. In growth-restricted human fetuses DV shunting is increased and the umbilical
      blood supply to the fetal liver is reduced. The long-term reduction of the
      hepatic blood supply may be involved in fetal growth restriction. The occlusion
      of the DV leads to a significant increase in cell proliferation in fetal skeletal
      muscle, heart, kidneys and liver, and possibly to an increase in insulin-like
      growth factor (IGF)-I and -II mRNA expression in the fetal liver. These findings
      hint at the possible role of the perfusion of the fetal liver in the control of
      the growth process. The quantification of DV shunting by Doppler velocimetry may
      improve the early recognition of fetal compromise in prenatal medicine. In this
      Review we summarize the published data on the anatomical structure and histology
      of the DV, the mechanisms of regulation of DV shunting, its role in fetal
      survival and growth and the possible use of the measurement of DV shunting in
      clinical practice.

PMID- 16565981
TI  - DISQ 4: serum CA 125 and benign looking adnexal masses.

PMID- 16565982
TI  - Predicting operative delivery.
AB  - OBJECTIVE: Unplanned operative delivery (vaginal or abdominal) is associated with
      maternal anxiety, maternal and neonatal morbidity and increased resource use. We
      aimed to identify potential predictors for emergency operative delivery. METHODS:
      This was a prospective observational study of 202 nulliparous women in a tertiary
      antenatal unit between 36 and 40 weeks' gestation. The assessment included an
      interview, a vaginal examination for Bishop score (optional), and a translabial
      ultrasound examination performed with the woman in a supine position and after
      voiding to determine cervical length, bladder position on Valsalva, and fetal
      head engagement. Clinical data were obtained from the institutional obstetric
      database and patient records. RESULTS: In the late third trimester, body mass
      index (P = 0.016), maternal age at due date (P < 0.0001), history of Cesarean
      section in first-degree relatives (P = 0.009), Bishop score (P = 0.0004),
      cervical length (P = 0.001), bladder position on Valsalva (P = 0.003) and head
      engagement (P < 0.0001) were significantly associated with delivery mode. On
      multivariate logistic regression analysis, the best model for predicting normal
      vaginal delivery contained maternal age, history of Cesarean section, Bishop
      score and bladder position on Valsalva and had excellent ability to discriminate
      between normal vaginal delivery and operative delivery (c = 0.85). The model with
      the best ability to discriminate between vaginal delivery and Cesarean section
      contained the same parameters plus body mass index; this model performed even
      better (c = 0.87). CONCLUSIONS: Identification of women at increased risk of
      operative delivery appears feasible. A combination of clinical and ultrasound
      variables yielded a model that is likely to predict delivery mode accurately in
      up to 87% of cases. Such a model may become useful as an entry criterion for
      intervention trials in women at low or very high risk of operative delivery.

PMID- 16565984
TI  - Designed synthesis of nanostructured siloxane-organic hybrids from amphiphilic
      silicon-based precursors.
AB  - This paper reports on recent progress in the synthesis of nanostructured siloxane
      organic hybrids based on the self-assembly of amphiphilic silicon-based
      precursors. A variety of ordered hybrid materials have been obtained by molecular
      design of the precursors. Alkoxysilanes and chlorosilanes with covalently
      attached hydrophobic organic tails are hydrolyzed to form amphiphilic molecules
      containing silanol groups, leading to the formation of layered (lamellar)
      structures. Transparent and oriented thin films of lamellar hybrids were prepared
      by the reaction in the presence of tetraalkoxysilane. In addition, the design of
      molecules having alkyl chains and large oligosiloxane heads led to the formation
      of mesophases consisting of cylindrical assemblies, providing a direct pathway to
      ordered porous silica. The synthesis, structural features, and formation
      processes of these hybrid mesostructures are discussed.

PMID- 16565983
TI  - Inedible mushrooms: a good source of biologically active substances.
AB  - In the course of our investigation on biologically active substances from
      inedible mushrooms in Japan, Germany, and Vietnam, we studied the chemical
      constituents of 22 species belonging to five families: Scutigeraceae,
      Polyporaceae, Xylariaceae, Thelephoraceae, and Paxillaceae. Various types of
      chemical substances were purified and characterized based on the modern
      spectroscopic methods and also on chemical reactions. These metabolites have
      shown a broad activity in many biological systems, such as antimicrobial,
      nematicidal, inhibition of NO production, anti-human immunodeficiency virus,
      tumor necrosis factor-alpha, and antioxidant activities. These isolated
      metabolites did not only show interesting activities, but also are employed as
      chemical markers supported for chemosystematics of these families. This review
      paper deals with the chemical constituents of 22 species, their biological
      activities, and also a discussion on chemosystematics.

PMID- 16565985
TI  - O-confusion approach in construction of carbaporphyrinoids.
AB  - Carbaporphyrinoids provide a suitable macrocyclic platform for organometallic
      investigations providing unique capabilities for reversible modifications of a
      macrocyclic structure. Alteration of a coordination core is the route of choice
      for stabilizing unusual metal ion oxidation states and coordination geometries.
      This concise review presents the general characteristic of carbaporphyrinoid
      focusing, however, on oxaporphyrin derivatives. Incorporation of a furan ring
      into a porphyrin frame results in the formation of 21-oxaporphyrin or its O
      confused counterpart. This particular couple, constructed applying the O
      confusion concept, was selected to illustrate the developments in the field of
      carbaporphyrinoids. The coordination chemistry in the O-confused porphyrin
      surrounding takes advantage of the unique set of four meridional donor atoms
      (CNNN) constrained in the regular porphyrin-like framework. The subtle interplay
      between their structural flexibility, perimeter substitution, coordination, and
      aromaticity was detected for oxacarbaporphyrinoids. The oxidation state of a
      central metal ion is a factor, which determines the ligand molecular structure.
      The adjacency of the metal and carbon atom provides the unprecedented route for
      activation of the carbocyclic moiety, which is built into a metalloporphyrin-like
      structure. The perspectives of the field have also been briefly discussed
      including feasible applications as a new class of building blocks applied to
      control both the architecture and electronic properties of oligoporphyrinic
      nanostructures.

PMID- 16565986
TI  - Astrocytes in 17beta-estradiol treated mixed hippocampal cultures show attenuated
      calcium response to neuronal activity.
AB  - Glial cells in the brain are capable of responding to hormonal signals. The
      ovarian steroid hormone 17beta-estradiol, in addition to its actions on neurons,
      can directly affect glial cells. Estrogen receptors have been described on both
      neurons and astrocytes, suggesting a complex interplay between these two in
      mediating the effects of the hormone. Astrocytes sense and respond to neuronal
      activity with a rise in intracellular calcium concentration ([Ca(2+)](i)). Using
      simultaneous electrophysiology and calcium imaging techniques, we monitored
      neuronal activity evoked astrocyte ([Ca(2+)](i)) changes in mixed hippocampal
      cultures loaded with fluo-3 AM. Action potential firing in neurons, elicited by
      injecting depolarizing current pulses, was associated with ([Ca(2+)](i))
      elevations in astrocytes, which could be blocked by 200 microM MCPG and also 1
      microM TTX. We compared astrocytic ([Ca(2+)](i)) transients in control and 24
      hour estradiol treated cultures. The amplitude of the ([Ca(2+)](i)) transient,
      the number of responsive astrocytes, and the ([Ca(2+)](i)) wave velocity were all
      significantly reduced in estradiol treated cultures. ([Ca(2+)](i)) rise in
      astrocytes in response to local application of the metabotropic glutamate
      receptor (mGluR) agonist t-ACPD was attenuated in estradiol treated cultures,
      suggesting functional changes in the astrocyte mGluR following 24-h treatment
      with estradiol. Since astrocytes can modulate synaptic transmission by release of
      glutamate, the attenuated ([Ca(2+)](i)) response seen following estradiol
      treatment could have functional consequences on astrocyte-neuron signaling.

PMID- 16565987
TI  - Inverse regulation of inducible nitric oxide synthase (iNOS) and arginase I by
      the protein tyrosine phosphatase SHP-1 in CNS glia.
AB  - We have previously shown that the SH2 domain-containing protein tyrosine
      phosphatase SHP-1 plays a critical role in controlling virus infection in CNS
      glia in vivo and in vitro. The present study addressed whether increased virus
      replication in SHP-1-deficient glia in vitro may be a result of altered
      expression of inducible nitric oxide synthase (iNOS/NOS2). First, we observed a
      profound reduction in iNOS protein expression and production of nitric oxide (NO)
      in response to the viral mimic double-stranded RNA (dsRNA), despite the induction
      of high levels of iNOS mRNA, in SHP-1-deficient motheaten mouse compared to wild
      type littermate mouse glia. Because both iNOS expression and NO production are
      suppressed by multiple pathways involving arginase I activity, it was important
      that we observed abnormally high constitutive expression of arginase I in
      cultured glia of SHP-1-deficient compared to wild type mice. Further, both
      constitutive and IL-4/IL-10-induced expression of arginase I correlated with
      elevated STAT6 nuclear binding activity, decreased NO production, and increased
      virus replication in motheaten compared to wild type astrocytes. These findings
      provide the first evidence of an inverse relationship between NO and arginase I
      activity regulated by SHP-1 in CNS glia that is relevant to modulation of innate
      anti-viral responses. Thus, we propose that SHP-1 is a critical regulator of
      innate immunity to virus infections in CNS cells.

PMID- 16565988
TI  - Further evidence for first-trimester risk assessment as an autonomy-enhancing
      strategy.

PMID- 16565989
TI  - Prediction of patient-specific risk of early preterm delivery using maternal
      history and sonographic measurement of cervical length: a population-based
      prospective study.
AB  - OBJECTIVE: To develop a model for calculating the patient-specific risk of
      spontaneous early preterm delivery by combining maternal factors and the
      transvaginal sonographic measurement of cervical length at 22 + 0 to 24 + 6
      weeks, and to compare the detection rate of this method to that achieved from
      screening by cervical length or maternal characteristics alone. METHODS: This was
      a population-based prospective multicenter study involving 40,995 unselected
      women with singleton pregnancies attending for routine hospital antenatal care in
      London, UK. Complete follow-up was obtained from 39,284 (95.8%) cases. The main
      outcomes were detection rate, false-positive rate and accuracy of predicting
      spontaneous delivery before 32 weeks' gestation. RESULTS: Spontaneous delivery
      before 32 weeks occurred in 235 (0.6%) cases. The detection rate of screening for
      early preterm delivery, at a fixed false-positive rate of 10%, was 38% for
      maternal factors, 55% for cervical length and 69% for combined testing. There was
      good agreement between the model estimates and the observed probabilities of
      preterm delivery. CONCLUSIONS: This study provides a model that can give an
      accurate patient-specific risk of preterm delivery. The detection rate of
      screening by a combination of maternal factors and the measurement of cervical
      length was substantially higher than that of screening by each method alone.

PMID- 16565990
TI  - The fetal circulation and essential organs-a new twist to an old tale.

PMID- 16565991
TI  - Nuchal translucency screening and anxiety levels in pregnancy and puerperium.
AB  - OBJECTIVES: To compare levels of anxiety and depression during pregnancy and
      puerperium between women who are offered nuchal translucency (NT) screening
      routinely and those who are not, and to compare levels between women accepting
      and those declining screening. METHODS: In 12 midwife practices in three
      different health districts an experimental NT screening program was offered to
      pregnant women between 1 June 1999 and 1 January 2001. As part of this
      implementation study, questionnaires including the Hospital Anxiety and
      Depression Scale (HADS) were completed: after the patient was informed but before
      screening (T1), at 20 weeks of gestation (T2), and 6 weeks after delivery (T3). A
      control group of women receiving routine prenatal care (i.e. no screening
      offered) also completed the HADS questionnaire at 12 and 20 weeks and after
      delivery. RESULTS: Five hundred and twenty-seven questionnaires were analyzed.
      There was a screening uptake of 87% in the intervention group (i.e. those offered
      screening). Women in this group differed significantly in the percentage of
      previous miscarriages and religious background compared with the control group.
      We adjusted for these differences in the analysis. There were no significant
      differences in HADS scores between the intervention and the control groups at T1,
      suggesting that women receiving information on screening were not more anxious
      compared with women who were not informed. Women who were offered screening
      (acceptors as well as decliners) had significantly lower HADS levels at 20 weeks
      and after delivery. There were no demographic differences between women accepting
      and those declining screening. CONCLUSION: Informing women and offering them NT
      screening for Down syndrome does not increase anxiety or depression levels in
      pregnancy. In fact, women undergoing or declining screening seem less anxious
      compared with those who are not offered screening. It is possible that informing
      women and offering them the chance to decide autonomously whether to participate
      in screening reduces anxiety levels.

PMID- 16565992
TI  - Antenatal diagnosis of non-previa placenta increta with histological
      confirmation.

PMID- 16565993
TI  - Right superior vena cava draining into the left atrium: prenatal diagnosis and
      postnatal management.
AB  - Right superior vena cava (RSVC) draining into the left atrium, causing hypoxemia,
      represents a very rare congenital malformation which has not previously been
      described in the fetus. We describe a case in which fetal echocardiography at 22
      weeks' gestation revealed an enlarged superior vena cava connecting abnormally
      with a mildly enlarged left atrium. Neonatal transthoracic echocardiography
      confirmed the diagnosis and showed an abnormal connection of the right pulmonary
      veins to the RSVC. Right-to-left shunt due to anomalous drainage of the RSVC into
      the left atrium associated with an atrial septal defect and anomalous pulmonary
      venous return were diagnosed on echocardiography and confirmed by angiography.
      The newborn was hemodynamically stable at birth and at the 1-year follow-up.

PMID- 16565994
TI  - Prediction of labor and delivery by transperineal ultrasound in pregnancies with
      prelabor rupture of membranes at term.
AB  - OBJECTIVE: To evaluate whether engagement of the fetal head or cervical length in
      women with premature rupture of membranes (PROM) at term, are associated with
      time from PROM to delivery or need for operative delivery. METHODS: A
      transperineal ultrasound examination was performed in 152 women with a single
      live fetus in cephalic presentation after PROM (at > 37 gestational weeks). The
      shortest distance from the outer bony limit of the fetal skull to the skin
      surface of the perineum was measured in a transverse view, and the cervical
      length was measured in a sagittal view. The time from PROM to delivery was tested
      in a Cox regression analysis with ultrasound measurements, parity, maternal age,
      body mass index and birth weight as possible predictive factors. RESULTS: The
      head-perineal distance was associated with the time from PROM to delivery (log
      rank test, P < 0.001). Thirty-six hours after PROM, 32% (95% CI, 15-49) of women
      with a short head-perineal distance (< 45 mm) and 43% (95% CI, 24-62) of women
      with a long distance (> or = 45 mm) were still in labor. Women with a short head
      perineal distance had fewer Cesarean sections, less use of epidural analgesia and
      a shorter time in active labor, and their babies had a higher pH in the umbilical
      artery. The measured cervical length was not associated independently with time
      to delivery. CONCLUSION: Transperineal ultrasound measurements of fetal head
      engagement may help clinicians to predict the course of labor in women with PROM.

PMID- 16565995
TI  - Dynamic cervical change: is real-time sonographic cervical shortening predictive
      of preterm delivery in patients with symptoms of preterm labor?
AB  - OBJECTIVES: To determine prospectively if dynamic cervical change (spontaneous
      real-time cervical shortening) is predictive of preterm delivery at < 37 weeks'
      gestation in patients with symptoms of preterm labor. METHODS: This was a
      prospective study of patients at 23-34 weeks' gestation who were symptomatic for
      preterm labor. Patients underwent a 10-min real-time sonographic cervical length
      assessment with measurements taken at 1-min intervals. The presence or absence of
      dynamic cervical change, defined as real-time changes in cervical length
      observable to the naked eye of the sonologist during the examination, was
      recorded. Gestational age at delivery was obtained from medical records. Preterm
      delivery was defined as delivery at < 37 weeks' gestation. Dynamic cervical
      change and initial and minimum cervical lengths were assessed for prediction of
      preterm delivery. RESULTS: Seventy-six patients were enrolled, and 66 were
      available for outcome analysis. Thirty-one patients (47%) exhibited dynamic
      cervical change. Patients with dynamic change had shorter initial cervical
      lengths (27 mm vs. 36 mm, P = 0.001), shorter minimum cervical lengths (20 vs. 33
      mm, P < 0.001) and larger changes in cervical length during the examination
      period (10 vs. 4 mm, P < 0.001). In the subgroup of patients with an initial
      cervical length > 30 mm, those with dynamic change delivered earlier than did
      those without dynamic change (36.8 vs. 38.6 weeks, P = 0.02), and a higher
      percentage delivered preterm (27% vs. 11%, odds ratio (OR), 3.0 (0.5-17.0)).
      Multivariate analysis showed that minimum cervical length was a better predictor
      of preterm delivery than was initial cervical length. CONCLUSIONS: Dynamic
      cervical change occurs frequently in association with shortened cervical length.
      In patients with longer initial cervical lengths, dynamic change may increase the
      risk for preterm delivery. When dynamic change is noted in a patient with preterm
      labor symptoms, use of the minimum cervical length observed may be better
      compared with initial cervical length for determining preterm delivery risk.

PMID- 16565996
TI  - Nifedipine therapy for preterm labor: effects on placental, fetal cerebral and
      atrioventricular Doppler parameters in the first 48 hours.
AB  - OBJECTIVE: To assess the effect of nifedipine tocolysis on Doppler parameters of
      the uterine, umbilical and fetal middle cerebral arteries and atrioventricular
      valves in the first 48 h of therapy. METHODS: Doppler waveforms of uterine,
      umbilical and middle cerebral arteries and both atrioventricular valves were
      measured from 28 pregnant women and fetuses prior to and during nifedipine
      therapy for preterm labor. Maternal and fetal heart rates (FHR), maternal
      systolic and diastolic blood pressure, and the Doppler pulsatility index (PI) of
      the uterine, umbilical and middle cerebral arteries were measured. The
      cerebroplacental ratio (middle cerebral artery PI/umbilical artery PI) was
      calculated. The total time velocity integrals (TVIs) of tricuspid and mitral
      valves and their E- and A-wave peak velocity ratio (E/A) were measured. Friedman
      repeated-measures analysis of variance was used to compare the variables before
      and after nifedipine therapy. If significant differences were found, Wilcoxon's
      signed ranks test was used to analyze the difference between the two variables. A
      P-value of < 0.05 was considered significant. RESULTS: Nifedipine maintenance was
      associated with a significant decline in maternal systolic and diastolic blood
      pressure after 24 h, while maternal heart rate and FHR were unaffected. The
      uterine artery PI had decreased significantly at 24 and 48 h, while the umbilical
      artery PI did not change significantly. The middle cerebral artery PI had
      decreased significantly at 24 and again at 48 h. A significant fall in the
      cerebroplacental Doppler ratio was maintained beyond 24 h. The mean E/A values,
      TVIs and TVI x FHR values at 24 and 48 h were unchanged from the baseline values.
      CONCLUSIONS: Nifedipine maintenance tocolysis is associated with a significant
      decline in uterine artery and middle cerebral artery Doppler indices 24 h after
      the first dose. Fetal cardiac diastolic function is unaffected and the
      significant redistribution observed after 24 h is likely to be attributable to
      altered cerebral blood flow.

PMID- 16565997
TI  - Influence of nuchal translucency screening on anxiety and depression levels in
      pregnancy and puerperium.

PMID- 16565998
TI  - Affect modulates appetite-related brain activity to images of food.
AB  - OBJECTIVE: We examined whether affect ratings predicted regional cerebral
      responses to high and low-calorie foods. METHOD: Thirteen normal-weight adult
      women viewed photographs of high and low-calorie foods while undergoing
      functional magnetic resonance imaging (fMRI). Regression analysis was used to
      predict regional activation from positive and negative affect scores. RESULTS:
      Positive and negative affect had different effects on several important appetite
      related regions depending on the calorie content of the food images. When viewing
      high-calorie foods, positive affect was associated with increased activity in
      satiety-related regions of the lateral orbitofrontal cortex, but when viewing low
      calorie foods, positive affect was associated with increased activity in hunger
      related regions including the medial orbitofrontal and insular cortex. The
      opposite pattern of activity was observed for negative affect. CONCLUSION: These
      findings suggest a neurobiologic substrate that may be involved in the commonly
      reported increase in cravings for calorie-dense foods during heightened negative
      emotions.

PMID- 16565999
TI  - Do supplementary items on the eating disorder examination improve the assessment
      of adolescents with anorexia nervosa?
AB  - OBJECTIVE: Given that adolescents with anorexia nervosa (AN) typically have lower
      scores on the Eating Disorder Examination (EDE) than expected, the current study
      examined whether the inclusion of eight supplementary items developed by the
      authors of the EDE better captured the symptoms of adolescents with AN. METHOD: A
      dataset consisting of EDEs from 86 adolescents was examined by 3 primary methods:
      (1) baseline subscale scores were compared before and after the addition of the
      supplementary items, (2) the internal consistency of the EDE with the addition of
      these items was examined, and (3) each of these items was compared before and
      after treatment. RESULTS: After the addition of the supplementary items, the
      Eating Concern and Weight Concern subscales were significantly increased, whereas
      the Restraint subscale was significantly decreased, and the Shape Concern
      subscale was unchanged. Internal consistency was improved on the Eating Concern,
      Weight Concern, and Shape Concern subscales, and was decreased on the Restraint
      subscale. Three of eight items showed a significant decrease with treatment.
      CONCLUSION: Although the addition of some of these eight supplementary items
      better captured the psychopathology of adolescents with AN, scores were still
      substantially below expected, indicating that the exploration of other methods of
      assessment is needed.

PMID- 16566000
TI  - Complementary stripes of phospholipase Cbeta3 and Cbeta4 expression by Purkinje
      cell subsets in the mouse cerebellum.
AB  - Transverse boundaries divide the cerebellar cortex into four transverse zones,
      and within each zone the cortex is further subdivided into a symmetrical array of
      parasagittal stripes. Several molecules believed to mediate long-term depression
      at the parallel fiber-Purkinje cell synapse are known to be expressed in stripes.
      We have therefore explored the distributions of phospholipase Cbeta3 and
      phospholipase Cbeta4, key components in the transduction of type 1 metabotropic
      glutamate receptor-mediated responses. The data reveal that both phospholipase
      Cbeta isotypes are expressed strongly in the mouse cerebellum in subsets of
      Purkinje cells. The two distributions are distinct and largely nonoverlapping.
      The pattern of phospholipase Cbeta3 expression is unique, revealing stripes in
      three of the four transverse zones and a uniform distribution in the fourth. In
      contrast, phospholipase Cbeta4 appears to be confined largely to the Purkinje
      cells that are phospholipase Cbeta3-negative. PLCbeta3 is restricted to the
      zebrin II-immunopositive Purkinje cell subset. Not all zebrin II-immunoreactive
      Purkinje cells express PLCbeta3: in lobules IX and X it is restricted to that
      zebrin II-immunopositive subset that also expresses the small heat shock protein
      HSP25. PLCbeta4 expression is restricted to, and coextensive with, the zebrin II
      immunonegative Purkinje cell subset. These nonoverlapping expression patterns
      suggest that long-term depression may be manifested differently between
      cerebellar modules.

PMID- 16566001
TI  - Multiple olfactory receptor neurons and their axonal projections in the antennal
      lobe of the honeybee Apis mellifera.
AB  - The poreplate sensilla of honeybees are equipped with multiple olfactory receptor
      neurons (ORNs), which innervate glomeruli of the antennal lobe (AL). We
      investigated the axonal projection pattern in glomeruli of the AL (glomerular
      pattern), formed by the multiple ORNs of individual poreplate sensilla. We used
      the different glomerular patterns to draw conclusions about the equipment of
      poreplate sensilla with different ORN types. ORNs of single poreplate sensilla
      were stained and analyzed by laser-scanning confocal microscopy and 3D software
      (AMIRA). In 13 specimens we found between 7 and 23 ORNs. This is in accordance
      with data found in the literature (5-35 ORNs) suggesting that all ORNs of the
      single poreplate sensilla were stained. The ORNs innervate the AL via all four
      sensory tracts (T1-T4), and glomeruli of the anterior part of the AL are more
      often innervated. Each ORN innervates a single glomerulus (uniglomerular), and
      all ORNs of one poreplate sensillum project to different glomeruli. Visual
      inspection and individual identification of glomeruli, based on the honeybee
      digital AL atlas, were used to evaluate mapping of glomeruli by a rigid
      transformation of the experimental ALs onto a reference AL. ORNs belonging to
      individual poreplate sensilla form variable glomerular patterns, and we did not
      find a common organization of glomerular patterns. We conclude that poreplate
      sensilla are equipped with different ORN types but that the same ORN types can be
      found in different poreplate sensilla. The equipment of poreplate sensilla with
      ORNs is overlapping. The mapping of glomeruli by rigid transformation is revealed
      to be a powerful tool for comparative neuroanatomy.

PMID- 16566002
TI  - Identification, physiological actions, and distribution of VYRKPPFNGSIFamide
      (Val1)-SIFamide) in the stomatogastric nervous system of the American lobster
      Homarus americanus.
AB  - In this study, the peptide VYRKPPFNGSIFamide (Val(1)-SIFamide) was identified in
      the stomatogastric nervous system (STNS) of the American lobster, Homarus
      americanus, using matrix-assisted laser desorption/ionization-Fourier transform
      mass spectrometry (MALDI-FTMS). When bath-applied to the stomatogastric ganglion
      (STG), synthetic Val(1)-SIFamide activated the pyloric motor pattern, increasing
      both burst amplitude and duration in the pyloric dilator (PD) neurons. To
      determine the distribution of this novel SIFamide isoform within the lobster STNS
      and neuroendocrine organs, a rabbit polyclonal antibody was generated against
      synthetic Val(1)-SIFamide. Whole-mount immunolabeling with this antibody showed
      that this peptide is widely distributed within the STNS, including extensive
      neuropil staining in the STG and commissural ganglia (CoGs) as well as
      immunopositive somata in the CoGs and the oesophageal ganglion. Labeling was also
      occasionally seen in the pericardial organ (PO), but not in the sinus gland. When
      present in the PO, labeling was restricted to fibers-of-passage and was never
      seen in release terminals. Adsorption of the antibody by either Val(1)-SIFamide
      or Gly(1)-SIFamide abolished all Val(1)-SIFamide staining within the STNS,
      including the STG neuropil, whereas adsorption by other lobster neuropeptides had
      no effect on immunolabeling. These data strongly suggest that the staining we
      report is a true reflection of the distribution of this peptide in the STNS.
      Collectively, our mass spectrometric, physiological, and anatomical data are
      consistent with Val(1)-SIFamide serving as a locally released neuromodulator in
      the lobster STG. Thus, our study provides the first direct demonstration of
      function for an SIFamide isoform in any species.

PMID- 16566004
TI  - Topographical projection from the hippocampal formation to the amygdala: a
      combined anterograde and retrograde tracing study in the rat.
AB  - The hippocampal formation and amygdala are responsible for regulating emotion,
      learning, and behavior. The hippocampal projection to the amygdala has been
      demonstrated to originate in the subiculum and adjacent portion of field CA1 of
      the Ammon's horn (Sub/CA1) in the rat; however, the topographical organization of
      this pathway is still understudied. To make it clear, we performed anterograde
      and retrograde tracing with biotinylated dextran amine (BDA) and cholera toxin B
      subunit (CTb), respectively, in the rat. A series of BDA experiments revealed
      that the temporal-to-septal axis of origin determined a medial-to-lateral axis of
      termination in the amygdala. Briefly, the temporal region of the Sub/CA1 projects
      preferentially to the medial amygdaloid region including the medial,
      intercalated, and basomedial nuclei and the amygdalohippocampal transition area,
      and progressively more septal portions of the Sub/CA1 distribute their efferents
      in more lateral regions of the amygdala. Sub/CA1 fibers distributed in the
      central amygdaloid nucleus were relatively few. Retrograde tracing with CTb
      confirmed this topography and revealed little hippocampal innervation of the
      central nucleus of the amygdala. These observations suggest that distinct Sub/CA1
      regions arranged along the longitudinal hippocampal axis may influence distinct
      modalities of the amygdala function.

PMID- 16566003
TI  - Projections of the second cervical dorsal root ganglion to the cochlear nucleus
      in rats.
AB  - Physiological, anatomical, and clinical data have demonstrated interactions
      between somatosensory and auditory brainstem structures. Spinal nerve projections
      influence auditory responses, although the nature of the pathway(s) is not known.
      To address this issue, we injected biotinylated dextran amine into the cochlear
      nucleus or dorsal root ganglion (DRG) at the second cervical segment (C2).
      Cochlear nucleus injections retrogradely labeled small ganglion cells in C2 DRG.
      C2 DRG injections produced anterograde labeling in the external cuneate nucleus,
      cuneate nucleus, nucleus X, central cervical nucleus, dorsal horn of upper
      cervical spinal segments, and cochlear nucleus. The terminal field in the
      cochlear nucleus was concentrated in the subpeduncular corner and lamina of the
      granule cell domain, where endings of various size and shapes appeared.
      Examination under an electron microscope revealed that the C2 DRG terminals
      contained numerous round synaptic vesicles and formed asymmetric synapses,
      implying depolarizing influences on the target cell. Labeled endings synapsed
      with the stalk of the primary dendrite of unipolar brush cells, distal dendrites
      of presumptive granule cells, and endings containing pleomorphic synaptic
      vesicles. These primary somatosensory projections contribute to circuits that are
      hypothesized to mediate integrative functions of hearing.

PMID- 16566005
TI  - Cell division and cleavage orientation in the developing retina are regulated by
      L-DOPA.
AB  - Recent studies have highlighted a potential link between the cleavage orientation
      of a dividing neuroblast and the regulation of daughter cell fate in the
      developing vertebrate retina. There is evidence to suggest that this process is
      at least partially regulated by the presence of the retinal pigment epithelium
      (RPE) and/or RPE-derived factors. In addition to a lack of melanin in the RPE,
      the albino retina is characterized by abnormal patterns of cell proliferation and
      cellular organization during development as well as cell-type specific deficits
      in the adult. We examined mitotic spindle orientation in vivo in developing
      pigmented and albino rat retinae along with other parameters of cell division to
      determine whether RPE abnormalities in the albino influence these aspects of
      retinal development. In the albino, mitotic indices were elevated, an excess of
      cells remained in the cell cycle, dividing cells were not so tightly apposed to
      the ventricular margin, and an excessive proportion of divisions was vertically
      oriented (i.e., with the mitotic spindle aligned perpendicular to the plane of
      the neuroepithelium). Administration of L-DOPA (a melanin precursor found at
      reduced concentrations in the hypopigmented eye) regulated the distribution of
      spindle orientations and reduced levels of mitosis in a manner consistent with an
      endogenous role in the control of these processes. These findings highlight the
      multiple roles that L-DOPA plays in the regulation of retinal development and
      cast light on the diversity of anatomical abnormalities found in the albino
      visual system. J. Comp. Neurol. 496:369-381, 2006. (c) 2006 Wiley-Liss, Inc.

PMID- 16566006
TI  - Organization of dye-coupled cerebellar granule cells labeled from afferent
      vestibular and dorsal root fibers in the frog Rana esculenta.
AB  - Application of neurobiotin to the nerves of individual labyrinthine organs and
      dorsal root fibers of limb-innervating segments of the frog resulted in labeling
      of granule cells in the cerebellum showing a significant overlap with a partial
      segregation in the related areas of termination. In different parts of the
      cerebellum, various combinations of different canal and otolith organ-related
      granule cells have been discerned. The difference in the extension of territories
      of vertical canals vs. horizontal canals may reflect their different involvement
      in the vestibuloocular and vestibulospinal reflex. Dye-coupled cells related to
      the lagenar and saccular neurons were localized in more rostral parts of the
      cerebellum, whereas cells of the utricle were represented only in its caudal
      half. This separation is supportive of the dual function of the lagena and the
      saccule. The territories of granule cells related to the cervical and lumbar
      segments of the spinal cord were almost completely separated along the
      rostrocaudal axis of cerebellum, whereas their territories were almost entirely
      overlapping in the mediolateral and ventrodorsal directions. The partial overlap
      of labyrinthine organ-related and dorsal root fiber-related granule cells are
      suggestive of a convergence of sensory modalities involved in the sense of
      balance. We propose that the afferent input of vestibular and proprioceptive
      fibers mediated by gap junctions to the cerebellar granule cells subserve one of
      the possible morphological correlates of a very rapid modification of the motor
      activity in the vestibulocerebellospinal neuronal circuit.

PMID- 16566007
TI  - Architectonic organization of the inferior parietal convexity of the macaque
      monkey.
AB  - The inferior parietal lobule (IPL) of the macaque monkey constitutes the largest
      part of Brodmann's area 7. Functional, connectional, and architectonic data have
      indicated that area 7 is comprised of several distinct sectors located in the
      lateral bank of the intraparietal sulcus and on the IPL cortical convexity. To
      date, however, attempts to parcellate the IPL based on architectonic criteria
      have been controversial, and correlation between anatomical and functional data
      has been inadequate. In the present study we aimed to determine the number and
      extent of cytoarchitectonically distinct areas occupying the IPL convexity. To
      this end, we studied the cytoarchitecture and myeloarchitecture of this region in
      28 hemispheres of 17 macaque monkeys. Four distinct areas were identified at
      different rostrocaudal levels along the IPL convexity and were defined as PF,
      PFG, PG, and Opt, with area PF corresponding to the rostralmost area and area Opt
      to the caudalmost one. All areas extend dorsally up to the lateral bank of the
      intraparietal sulcus, for about 1-2 mm. Areas PF, PFG, and PG border ventrally on
      opercular areas, whereas area Opt extends ventrally into the dorsal bank of the
      superior temporal sulcus. Analysis of the distribution of SMI-32 immunoreactivity
      confirmed the proposed parcellation scheme. Some additional connectional data
      showed that the four areas project in a differential way to the premotor cortex.
      The present data challenge the current widely used subdivision of the IPL
      convexity into two areas, confirming, but also extending the subdivision
      originally proposed by Pandya and Seltzer.

PMID- 16566010
TI  - Multiple sclerosis: tip of the iceberg?

PMID- 16566008
TI  - Immunolocalization of the Ca2+-activated K+ channel Slo1 in axons and nerve
      terminals of mammalian brain and cultured neurons.
AB  - Ca(2+)-activated voltage-dependent K(+) channels (Slo1, KCa1.1, Maxi-K, or BK
      channel) play a crucial role in controlling neuronal signaling by coupling
      channel activity to both membrane depolarization and intracellular Ca(2+)
      signaling. In mammalian brain, immunolabeling experiments have shown staining for
      Slo1 channels predominantly localized to axons and presynaptic terminals of
      neurons. We have developed anti-Slo1 mouse monoclonal antibodies that have been
      extensively characterized for specificity of staining against recombinant Slo1 in
      heterologous cells, and native Slo1 in mammalian brain, and definitively by the
      lack of detectable immunoreactivity against brain samples from Slo1 knockout
      mice. Here we provide precise immunolocalization of Slo1 in rat brain with one of
      these monoclonal antibodies and show that Slo1 is accumulated in axons and
      synaptic terminal zones associated with glutamatergic synapses in hippocampus and
      GABAergic synapses in cerebellum. By using cultured hippocampal pyramidal neurons
      as a model system, we show that heterologously expressed Slo1 is initially
      targeted to the axonal surface membrane, and with further development in culture,
      become localized in presynaptic terminals. These studies provide new insights
      into the polarized localization of Slo1 channels in mammalian central neurons and
      provide further evidence for a key role in regulating neurotransmitter release in
      glutamatergic and GABAergic terminals.

PMID- 16566011
TI  - Prime minister's illness underscores remaining question in stroke care.

PMID- 16566009
TI  - Unique combination of anatomy and physiology in cells of the rat paralaminar
      thalamic nuclei adjacent to the medial geniculate body.
AB  - The medial geniculate body (MGB) has three major subdivisions, ventral (MGV),
      dorsal (MGD), and medial (MGM). MGM is linked with paralaminar nuclei that are
      situated medial and ventral to MGV/MGD. Paralaminar nuclei have unique inputs and
      outputs compared with MGV and MGD and have been linked to circuitry underlying
      some important functional roles. We recorded intracellularly from cells in the
      paralaminar nuclei in vitro. We found that they possess an unusual combination of
      anatomical and physiological features compared with those reported for "standard"
      thalamic neurons seen in the MGV/MGD and elsewhere in the thalamus. Compared with
      MGV/MGD neurons, anatomically, 1) paralaminar cell dendrites can be long, branch
      sparingly, and encompass a much larger area; 2) their dendrites may be smooth but
      can have well defined spines; and 3) their axons can have collaterals that branch
      locally within the same or nearby paralaminar nuclei. When compared with MGV/MGD
      neurons, physiologically, 1) their spikes are larger in amplitude and can be
      shorter in duration; 2) their spikes can have dual afterhyperpolarizations with
      fast and slow components; and 3) they can have a reduction or complete absence of
      the low-threshold, voltage-sensitive calcium conductance that reduces or
      eliminates the voltage-dependent burst response. We also recorded from cells in
      the parafascicular nucleus, a nucleus of the posterior intralaminar nuclear
      group, because they have unusual anatomical features that are similar to those of
      some of our paralaminar cells. As with the labeled paralaminar cells,
      parafascicular cells had physiological features distinguishing them from typical
      thalamic neurons.

PMID- 16566013
TI  - Non-eIF2B-related cystic leukoencephalopathy of unknown origin.

PMID- 16566012
TI  - Insular involvement in brain infarction increases risk for cardiac arrhythmia and
      death.
AB  - OBJECTIVE: Brain injuries may induce cardiac dysrhythmias and sudden cardiac
      death. METHODS: We analyzed 12-lead electrocardiograms of 493 consecutive
      patients with brain infarction (BI) proved by an magnetic resonance imaging and
      493 control subjects matched for age, sex, and center. Insular involvement
      (insula (+/-)) was assessed by two independent readings of the magnetic resonance
      imaging scans. Cases were followed for 5 years. RESULTS: Acute BI was
      independently associated with heart rate (< or = 64 beats/min), abnormal
      repolarization, atrial fibrillation, and ventricular and supraventricular ectopic
      beats. Lower heart rate in BI patients was due to an interaction with smoking (p
      for interaction = 0.004). Insula(+) group was significantly associated with
      abnormal repolarization with no interaction with infarct side. Atrial
      fibrillation by history was also more frequent in the insula(+) than in the
      insula(-) group (p = 0.07). After adjustment for age, sex, cardiovascular
      history, and handicap at admission, right insula(+) BI was significantly
      associated with 2-year all-cause death (hazard ratio, 2.11; 95% confidence
      interval, 1.27-3.52) and with vascular death (hazard ratio, 2.00; 95% confidence
      interval, 1.00-3.93). In multivariate analysis including age, sex, cardiovascular
      history, handicap at admission, and lesion side, increased QTc interval and left
      bundle branch block were independent predictors of all-cause and vascular
      mortality at 2 years in right insula(+) patients. INTERPRETATION: These findings
      support the notion that right insular involvement may lead to
      electrocardiographic abnormalities with potential prognostic implications. This
      could be important for optimal care in patients with right insular infarct.

PMID- 16566014
TI  - Toxic brainstem encephalopathy after artemisinin treatment for breast cancer.

PMID- 16566015
TI  - Improvement or progression in childhood cerebral arteriopathies: current
      difficulties in prediction and suggestions for research.

PMID- 16566016
TI  - Movement-related cortical potentials in primary lateral sclerosis.
AB  - OBJECTIVE: Some patients with primary lateral sclerosis (PLS) have a clinical
      course suggestive of a length-dependent dying-back of corticospinal axons. We
      measured movement-related cortical potentials (MRCPs) in these patients to
      determine whether cortical functions that are generated through short,
      intracortical connections were preserved when functions conducted by longer
      corticospinal projections were impaired. METHODS: An electroencephalogram was
      recorded from scalp electrodes of 10 PLS patients and 7 age-matched healthy
      control subjects as they made individual finger-tap movements on a keypad. MRCPs
      were derived from back-averaging the electroencephalogram to the movement.
      RESULTS: MRCPs produced by finger taps were markedly reduced in PLS patients,
      including components generated by premotor areas of the cortex as well as the
      primary motor cortex. In contrast, the beta-band event-related desynchronization
      from the motor cortex was preserved. INTERPRETATION: These findings suggest that
      impairment in PLS is not limited to the distal axons of corticospinal neurons,
      but also affects neurons within the primary motor cortex and premotor cortical
      areas. The loss of the MRCP may serve as a useful marker of upper motor neuron
      dysfunction. Preservation of event-related desynchronization suggests that the
      cells of origin differ from the large pyramidal cells that generate the MRCP.

PMID- 16566017
TI  - Leigh's disease due to a new mutation in the PDHX gene.
AB  - OBJECTIVE: To describe the clinical course, neuroradiological presentation,
      biochemical and molecular studies of a new patient with pyruvate dehydrogenase
      complex (PDHc) deficiency. To compare this case with the data on other published
      cases. METHODS: Brain magnetic resonance imaging (MRI), basal metabolic
      investigations with lactate measurements in body fluids, PDHc activity assay on
      cultured skin fibroblasts, immunoblot analysis and molecular studies (polymerase
      chain reaction [PCR] and sequencing procedures). RESULTS: Our patient accused an
      unspecific encephalopathy for years and presented at 13 years of age an acute
      deterioration with basal ganglia necrosis and subcortical white matter
      involvement. PDHc deficiency was secondary to a large deletion (3913 bp) in the
      PDHX gene, which encodes E3 binding protein (E3BP) subunit. INTERPRETATION: These
      data provide an additional case of E3BP deficiency with a unique and previously
      unreported deletion in the PDHX gene.

PMID- 16566019
TI  - Reply to Prilipko et al.

PMID- 16566018
TI  - Microphthalmia and brain atrophy: a novel neurodegenerative disease.
AB  - OBJECTIVE: To delineate the features of a novel neurodegenerative disease.
      METHODS: We report three children of three related families with congenital
      microphthalmia and blindness, and progressive spasticity, microcephaly, seizures,
      and profound mental retardation. RESULTS: A magnetic resonance imaging scan was
      normal at birth. However, follow-up studies showed progressive atrophy involving
      the cerebral white matter and cortex, cerebellum, brainstem, and corpus callosum.
      The white matter changes extended into the subcortical region leaving only small
      islands of remaining cortical tissue. Known metabolic conditions involving white
      matter degeneration were excluded. INTERPRETATION: We propose this to be a novel
      autosomal recessive neurodegenerative disorder to be coined MOBA (microphthalmia
      brain atrophy) disease.

PMID- 16566020
TI  - Neuropathology of dementia in Parkinson's disease.

PMID- 16566021
TI  - The Parkinson's complex: parkinsonism is just the tip of the iceberg.

PMID- 16566022
TI  - Magnetic resonance imaging as a surrogate outcome measure of disability in
      multiple sclerosis: have we been overly harsh in our assessment?
AB  - OBJECTIVE: The validity of magnetic resonance imaging (MRI) as a surrogate
      outcome measure in multiple sclerosis (MS) clinical trials has been greeted
      skeptically both by the US Food and Drug Administration and by clinical
      researchers because the correlation between current MRI measures and clinical
      disability, although significant, has generally been low. Thus, the reported
      correlations have varied between rho = 0.09 and rho = 0.60, and have often been
      at the lower end of this range. Nevertheless, it still appears possible that this
      apparently poor correlation is due not to any deficiency either with our current
      MRI measures or with our disability scale, but rather to the intrinsic
      variability in the clinical expression of MS plaques in different anatomical
      locations. METHODS: This article explores this possibility through the
      development of a general mathematical model for the relation between MRI changes
      and clinical disability in patients with MS. RESULTS: Under the conditions of
      this general model, the maximum expected correlation between clinical disability
      and MRI will typically be quite low (eg, rho = 0.2-0.3), even when it is assumed
      that the MRI changes are the sole determinant of disability and, furthermore,
      that the scale used to measure disability is ideal. INTERPRETATION: These
      observations, together with the significant relations already reported between
      MRI and disability (with observed correlations in the range of 0.2-0.6), actually
      suggest that our available clinical and MRI measures are considerably better than
      is currently believed and, in fact, that the MRI may be a valid surrogate marker
      in the assessment of treatment efficacy in MS.

PMID- 16566023
TI  - An association between type 1 diabetes and idiopathic generalized epilepsy.

PMID- 16566024
TI  - Anti-glutamic acid decarboxylase anti-bodies--the missing link between epilepsy
      and diabetes.

PMID- 16566026
TI  - Phospholipase A2 and spinal cord injury: a novel target for therapeutic
      intervention.

PMID- 16566027
TI  - Advances in neurological education: a time to share.

PMID- 16566028
TI  - Perfusion computed tomography: prediction of final infarct extent and stroke
      outcome. Reply.

PMID- 16566029
TI  - Revisions to the 2001 McDonald diagnostic criteria.

PMID- 16566030
TI  - Tuberculosis of the endothoracic fascia.
AB  - A 13-year-old boy presented with a history of respiratory infection that had
      progressed for 3 months. A chest X-ray showed pathological findings that
      suggested endothoracic fascia compromise (Skarby sign). The thorax computerized
      axial tomography scan revealed multiple opacities in the fascia. A biopsy was
      performed, and a pathological lymph node with caseous material was obtained.
      Thirty days later, Mycobacterium tuberculosis var. hominis was obtained from the
      culture. The diagnosis of tuberculosis of the endothoracic fascia was confirmed.
      Treatment included 9 months with isoniacide and rifampin, and 2 months with
      pirazynamide and streptomycin, with excellent response. Vitamin B6 was added.

PMID- 16566031
TI  - Electronic processing of manuscripts.

PMID- 16566032
TI  - Deterministic and statistical methods for reconstructing multidimensional NMR
      spectra.
AB  - Reconstruction of an image from a set of projections is a well-established
      science, successfully exploited in X-ray tomography and magnetic resonance
      imaging. This principle has been adapted to generate multidimensional NMR
      spectra, with the key difference that, instead of continuous density functions,
      high-resolution NMR spectra comprise discrete features, relatively sparsely
      distributed in space. For this reason, a reliable reconstruction can be made from
      a small number of projections. This speeds the measurements by orders of
      magnitude compared to the traditional methodology, which explores all evolution
      space on a Cartesian grid, one step at a time. Speed is of crucial importance for
      structural investigations of biomolecules such as proteins and for the
      investigation of time-dependent phenomena. Whereas the recording of a suitable
      set of projections is a straightforward process, the reconstruction stage can be
      more problematic. Several practical reconstruction schemes are explored. The
      deterministic methods-additive back-projection and the lowest-value algorithm
      derive the multidimensional spectrum directly from the experimental projections.
      The statistical search methods include iterative least-squares fitting, maximum
      entropy, and model-fitting schemes based on Bayesian analysis, particularly the
      reversible-jump Markov chain Monte Carlo procedure. These competing
      reconstruction schemes are tested on a set of six projections derived from the
      three-dimensional 700-MHz HNCO spectrum of a 187-residue protein (HasA) and
      compared in terms of reliability, absence of artifacts, sensitivity to noise, and
      speed of computation.

PMID- 16566033
TI  - Pharmacokinetics, pharmacodynamics, and hepatitis C viral kinetics during
      antiviral therapy: the null responder.
AB  - Our aim was to study the effect of ribavirin on viral kinetics and to study the
      early patterns of response to antiviral therapy of hepatitis C and their
      correlation with interferon pharmacokinetics and pharmacodynamics. We conducted a
      randomized, controlled trial of peginterferon alfa-2a with or without ribavirin
      in interferon naive patients with HCV genotype 1. HCV RNA levels were measured at
      frequent intervals during treatment together with serum levels of peginterferon
      alfa-2a and 2'5'oligoadenylate synthetase (OAS). Of 29 patients treated, 14 had a
      complete response at day 29 while 15 had a null response (less than 1 log decline
      in HCV RNA). There were no significant differences between complete and null
      responders with regard to gender, age, race, body mass index, HCV subtype,
      baseline HCV RNA levels, serum aminotransferase activities, stage of fibrosis,
      peak OAS, or interferon levels. Mean serum IFN levels at day 29 and OAS levels at
      day 3 were no different between complete and null responders (15,525 vs. 30,768
      pg/ml and 2,044 vs. 2,323 pM/hr, respectively, P = n.s.). Addition of ribavirin
      to pegylated IFN did not significantly affect day 29 IFN levels or Day 3 OAS
      levels. In conclusion, null responders to either peginterferon alone or in
      combination with ribavirin have little or no decrease in serum HCV RNA early in
      therapy and rarely go on to achieve sustained virologic response and have no
      apparent host differences than complete responders, suggesting that interferon
      resistance in these patients may be virally rather than host-determined.

PMID- 16566036
TI  - Anencephaly and twins.

PMID- 16566035
TI  - Prenatal phenotypic overlap of Costello syndrome and severe Noonan syndrome by
      tri-dimensional ultrasonography.
AB  - BACKGROUND: Prenatal diagnosis of multiple congenital anomalies is difficult, and
      usually molecular biology cannot immediately confirm the suspected syndrome.
      Fetal dysmorphology is useful tool in the diagnosis process, with limitations.
      METHODS: We report the thorough prenatal investigation by 2D and 3D
      ultrasonography in a case of suspected Costello syndrome. RESULTS: Prenatal
      abnormalities were: increased nuchal translucency, polyhydramnios, bilateral
      pyelectasis and ventriculomegaly. Ultrasonographic morphological fetal face
      analysis found abnormal thickness of the skin in the prefrontal area, thick
      dysplastic ears, thick lips and deep-set creases in the hands and feet. As
      Costello and Noonan syndromes overlap, a PTPN11 analysis was done, with presence
      of a mutation (T854C). CONCLUSION: Prenatal overlap of feature of severe Noonan
      syndrome and Costello syndrome is confirmed, with dysmorphological similarities,
      due to edema of fetal skin in face and extremities.

PMID- 16566037
TI  - Cystic hygroma and omphalocele at 11 weeks in a fetus with monosomy X.

PMID- 16566038
TI  - Fetal enterolithiasis: prenatal sonographic and MRI diagnosis in two cases of
      urorectal septum malformation (URSM) sequence.
AB  - OBJECTIVES: Enterolithiasis (multiple calcifications of intraluminal meconium) is
      a rare, prenatal ultrasonographic finding. In this study, our aim was to evaluate
      the prenatal diagnostic features and discuss the management of the patients.
      METHODS: The data of two cases of prenatally diagnosed fetal enterolithiasis were
      collected from ultrasound scan, magnetic resonance imaging (MRI) and neonatal or
      postnatal autopsy records. The findings were evaluated in both prenatal and
      postnatal periods. Chromosomal analysis was performed in one case. An evaluation
      of primary and secondary malformations was done. Coexisting anomalies were
      searched for via radiology, neonatal surgery and histopathology. RESULTS:
      Malformations in two cases (both males) with partial and complete urorectal
      septum malformation (URSM) sequence were described. The absence of an anal
      opening and presence of a fistula between the urinary and gastrointestinal tract
      were common findings. These features were considered as primary malformations
      contributing to the formation of enterolithiasis. Secondary anomalies (urinary
      and gastrointestinal system malformations, pulmonary hypoplasia, genital and
      other coexisting anomalies) were evaluated. CONCLUSIONS: The prenatal detection
      of enterolithiasis carries a poor prognosis. Most of the previously reported
      cases were invariably associated with major fetal malformations of the urinary
      and gastrointestinal tract. It is a warning sign for large bowel obstruction with
      or without enterourinary fistula. Therefore, adequate gastrointestinal and
      urologic studies must be undertaken after birth for the final diagnosis. There is
      a high mortality rate in the reported cases, mostly attributed to associated
      anomalies, and all survivors required neonatal surgery. It is important to
      differentiate the partial from the full URSM sequence because the prognosis in
      the partial URSM sequence is generally good, with long-term survival being
      common.

PMID- 16566039
TI  - Prenatal diagnosis of low-level mosaicism for a small XIST-negative supernumerary
      ring X chromosome in a nondysmorphic male fetus.

PMID- 16566041
TI  - Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD)
      without DNA from an index patient in a current pregnancy.

PMID- 16566043
TI  - Prenatal identification of small supernumerary marker chromosomes by FISH in an
      infant born with mild congenital anomalies.

PMID- 16566042
TI  - Karyotype and outcome of fetuses diagnosed with cystic hygroma in the first
      trimester in relation to nuchal translucency thickness.
AB  - OBJECTIVES: To determine the incidence and to examine the karyotype and the
      outcome of fetuses diagnosed with cystic hygroma (CH) at 11-14 weeks of
      gestation. METHODS: The presence of bilateral cystic anechoic cavities in the
      neck, nuchal translucency (NT), malformations and hydrops was prospectively
      recorded in 6894 ultrasound examinations in the first trimester, between 2001 and
      2004. RESULTS: Forty-two fetuses (0.62%) were diagnosed with CH in the first
      trimester of pregnancy and 60% of these had an abnormal karyotype. NT was > or =
      3 mm in 83% and hydrops was present in 40% of the cases. The karyotype was
      abnormal in 25 (69%) of these, showing trisomy 18 and 45,XO more often than
      trisomy 21. NT was <3 mm in seven cases (17%); no hydrops was present and only
      one had an abnormal karyotype (47 + 18). Eight babies with CH without aneuploidy
      or hydrops were born alive, seven among them were without malformations and are
      developing normally at 1 to 18 months of age, the remaining one presented with
      CHARGE syndrome. CONCLUSIONS: CH is an independent entity from NT and its
      association with increased NT carries a poor prognosis.

PMID- 16566044
TI  - Doubtful association between TAR syndrome and increased nuchal translucency in
      the first trimester of pregnancy.

PMID- 16566045
TI  - Prenatal diagnosis of type II osteogenesis imperfecta, describing a new mutation
      in the COL1A1 gene.

PMID- 16566046
TI  - Development of antiviral fusion inhibitors: short modified peptides derived from
      the transmembrane glycoprotein of feline immunodeficiency virus.
AB  - Feline immunodeficiency virus (FIV) is a naturally occurring pathogen that causes
      an AIDS-like syndrome in domestic cats and is a valuable model system by which
      criteria for antiviral vaccines and drugs development can be tested. The cell
      entry step of the lentivirus life cycle is regarded as a promising target for the
      development of new generation inhibitors. We have previously described potent in
      vitro anti-FIV activity associated with a synthetic octapeptide, termed C8 (Ac
      Trp-Glu-Asp-Trp-Val-Gly-Trp-Ile-NH2), containing the Trp-rich motif of FIV
      transmembrane glycoprotein, which shares a common structural framework with the
      corresponding molecule of HIV and appears to play a similar role in cell entry.
      In this report, in an attempt to develop simpler potential fusion inhibitors to
      be tested in vivo, we describe further studies focused on synthetic peptide
      analogues of C8. Since C8 inhibitory activity is dependent upon the Trp motif, we
      systematically replaced these residues with bulky and/or aromatic natural and
      unnatural amino acids, in order to develop a rational structure-activity
      relationship. Furthermore, the amino acids located between the Trp residues,
      which are not crucial for inhibitory activity, were replaced by simple alkyl
      spacers of appropriate length. Design, NMR structural analysis, in vitro anti-FIV
      activity in lymphoid cell cultures, and serum stability of these new analogues
      are reported. The final results indicate that a simpler hexapeptide (Ac-Nal2-Ape
      Nal2-Ape-Nal2-Ile-NH2; Nal2 = 3-naphthalen-2-yl-L-alanine, Ape = 5-aminopentanoic
      acid), almost entirely made up of unnatural amino acid residues, has markedly
      increased enzymatic stability, while maintaining strong antiviral potency in
      vitro.

PMID- 16566047
TI  - Selective hydroxylation of highly branched fatty acids and their derivatives by
      CYP102A1 from Bacillus megaterium.
AB  - Highly branched fatty acids, the main components of the preen-gland waxes of the
      domestic goose and the Muscovy duck, and their derivatives are promising chiral
      precursors for the synthesis of macrolide antibiotics. The key step in the
      utilisation of these compounds is their regioselective hydroxylation, which
      cannot be achieved in a classical chemical approach. Three P450 monooxygenases,
      CYP102A1, CYP102A2 and CYP102A3, demonstrating high turnover numbers in the
      hydroxylation of iso and anteiso fatty acids (>400 min(-1)), were tested for
      their activity towards these substrates. CYP102A1 from Bacillus megaterium and
      its A74G F87V L188Q triple mutant hydroxylate a variety of these substrates with
      high activity and regioselectivity. In all cases, the triple mutant showed much
      higher activities than the wild-type enzyme. The binding constants, determined
      for wild-type CYP102A1 and the triple mutant with tetramethylnonanol as
      substrate, were >200 microM and approximately 23 microM, respectively. Data
      derived from binding analysis support the differences in activity found for the
      wild-type CYP102A1 and the triple mutant. Surprisingly, CYP102A2 and CYP102A3
      from Bacillus subtilis did not show any activity. Substrate binding spectra,
      recorded to investigate substrate accessibility to the enzyme's active sites,
      revealed that the substrates either could not access the active site of the
      Bacillus subtilis monooxygenases, or did not come into proximity with the heme.

PMID- 16566048
TI  - Aptamer to ribozyme: the intrinsic catalytic potential of a small RNA.
AB  - The discovery of RNA-based catalysis 23 years ago dramatically changed the way
      biologists and biochemists thought of RNA. In the recent past, several ribozymes
      structures have provided some answers as to how catalysis is accomplished and how
      it relates to RNA structure and folding. However, there is still little
      information as to how catalytic activity evolved. Here we show that the small
      malachite green-binding aptamer has intrinsic catalytic potential that can be
      realized by designing the proper substrate. The charge distribution within the
      RNA binding pocket stabilizes the transition state of an ester hydrolysis
      reaction and thus accelerates the overall reaction. The results suggest that
      electrostatic forces can contribute significantly to RNA-based catalysis.
      Moreover, even simple RNA structures that have not been selected for catalytic
      properties can have a basic catalytic potential if they encounter the right
      substrate. This provides a possible starting point for the molecular evolution of
      more complex ribozymes.

PMID- 16566049
TI  - Inhibition and detection of galectins.
AB  - More and more studies report on the roles that galectins play in numerous types
      of cancer. These roles can be varied, as has been shown particularly for galectin
      3. These studies have created the need for inhibitors that can block unwanted
      effects, and the need to detect galectins in tissues, in order to better
      understand their role, and aid in diagnosis and prognosis. Since galectins bind
      beta-galactosides, monovalent galactose-derived inhibitors have been prepared but
      also peptidic ones have appeared. Since galectins often induce crosslinking and
      partake in aggregation phenomena, multivalency has been a successful design
      element in inhibitor development. Currently, there are no cheap and convenient
      solutions available for the detection of, ideally multiple, galectins in tissue
      samples, although antibody-based methods such as ELISA and Western blot analysis
      are being used. Besides these, a chemical probe-based method also shows potential
      as an alternative.

PMID- 16566050
TI  - o-Iodoxybenzoic acid (IBX): pKa and proton-affinity analysis.

PMID- 16566051
TI  - A dynamic random access memory based on a conjugated copolymer containing
      electron-donor and -acceptor moieties.

PMID- 16566052
TI  - Synthesis and characterization of stable ruthenabenzenes.

PMID- 16566053
TI  - Total synthesis of (-)-sarain A.

PMID- 16566054
TI  - Prenatal diagnosis and management of twin pregnancies complicated by a co
      existing molar pregnancy.

PMID- 16566055
TI  - Prenatal ultrasound and MRI predict placental localization in a combined
      intrauterine and extrauterine twin pregnancy.

PMID- 16566056
TI  - Prenatal diagnosis of bronchial atresia, early in pregnancy.

PMID- 16566057
TI  - Prenatal diagnosis of the fetal frontal encephalocele by three-dimensional
      ultrasound.

PMID- 16566058
TI  - Noninvasive genotyping of 9 Y-chromosome specific STR loci using circulatory
      fetal DNA in maternal plasma by multiplex PCR.
AB  - BACKGROUND: Human Y-Chromosome specific STR (Y-STR) has now become a useful loci
      in casework. However, noninvasive genotyping of multiple Y-STR loci and its
      application in prenatal genetic diagnosis haven't been reported. The purpose of
      this study is to develop a Y-STR multiplex PCR amplification system that is
      suitable for the amplification of short-sized templates of circulatory male fetal
      DNA and use the established multiplex in noninvasive prenatal genetic diagnosis
      and its further applications in forensic casework. METHODS: On the basis of the
      characteristic of circulatory fetal DNA in maternal plasma, we selected 9 Y-STR
      loci in which the allele size was less than 180 bp in length and developed two
      multiplexes that allowed fluorescent genotyping of 9 Y-STR loci simultaneously.
      These Y-STR loci include two trinucleotide repeats (DYS426 and DYS388) and seven
      tetranucleotide repeats (DYS393, DYS460, H4; DYS391, DYS389 I, DYS456 and
      DYS458). Sixty-four pairs of plasma DNA samples from pregnant women and genomic
      DNA samples from their husbands were detected by our method. RESULTS: As a
      result, an average of 7.3 Y-STR specific alleles was detected in each of the 30
      plasma DNA samples from pregnancies with male fetuses. However, none of these 9 Y
      STR specific alleles was detected in 34 plasma samples from pregnant women
      carrying female babies. The chances of detecting Y-STR alleles ranged from 66.7
      to 93.3%. Fifty-eight haplotypes were detected in 64 unrelated Chinese male
      individuals; haplotype diversity was 0.9966. This highly polymorphic Y-STR
      multiplex has greatly improved the chances of detecting the Y-STR allele.
      CONCLUSIONS: This assay provides a sensitive, accurate and efficient method for
      noninvasive prenatal genetic diagnosis and forensic casework.

PMID- 16566060
TI  - Intravenous administration of paclitaxel in Sprague-Dawley rats: what is a safe
      dose?
AB  - Few studies describe the administration of Taxol to rats; however, rats are
      typically used to study the toxicity of new drugs or novel formulations. A dose
      finding study was conducted to determine a safe dose of Taxol following
      intravenous administration in rats. Male Sprague-Dawley rats received a bolus of
      paclitaxel 5-20 mg/kg i.v. Blood was drawn before administration and at the
      following times after administration: 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 h.
      Plasma concentrations were determined using high performance liquid
      chromatography. Two rats received paclitaxel 20 mg/kg and died immediately. Nine
      rats received paclitaxel 10 mg/kg; seven of these rats died within 12 h and two
      rats were killed due to moribund conditions. Ten rats received paclitaxel 5 mg/kg
      with no morbidity. The following pharmacokinetics for paclitaxel in the plasma
      were estimated: C0, 8977 ng/ml; AUC(0 --> infinity), 7477 ng*h/ml; CL(s), 668
      ml/h*kg; V(ss), 1559 ml/kg; V(z) 2557 ml/kg and t(1/2), 2.6 h. It is concluded
      that further pharmacokinetic studies that are rationally designed to include
      appropriate measures of preclinical toxicity associated with paclitaxel are
      needed to identify formally the safest dose in rats following intravenous
      administration; however, these data indicate that male Sprague-Dawley rats can
      safely receive Taxol in a 5 mg/kg i.v. bolus.

PMID- 16566061
TI  - In Vitro metabolism of ciclesonide in human lung and liver precision-cut tissue
      slices.
AB  - Ciclesonide is a new-generation inhaled corticosteroid developed to treat the
      inflammation associated with persistent asthma. In order to identify the
      properties of ciclesonide responsible for anti-inflammatory activity, ciclesonide
      metabolism was investigated in human lung and liver precision-cut tissue slices.
      Three human lung and three human liver tissue slices were incubated with 25
      microM [14C]-ciclesonide for 2, 6 and 24 h. Cellular viability was assessed using
      adenosine 5'-triphosphate content and protein synthesis in lung slices and
      adenosine 5'-triphosphate content and potassium retention in liver slices.
      Ciclesonide and ciclesonide metabolites were analysed in tissue samples using
      high-performance liquid chromatography with ultraviolet and radiochemical
      detection. Metabolite identity was confirmed using mass spectrometry. In lung
      slices, the inactive parent compound, ciclesonide, was initially converted to the
      active metabolite, desisobutyryl-ciclesonide, and subsequently converted to fatty
      acid conjugates. The reversible formation of fatty acid conjugates was a major
      pathway of ciclesonide metabolism in human lung slices. The primary conjugate was
      identified as desisobutyryl-ciclesonide oleate. Ciclesonide was metabolized to at
      least five polar metabolites in the liver. Dihydroxylated desisobutyryl
      ciclesonide was the major polar metabolite in liver slices. Activation and fatty
      acid esterification in the lung followed by rapid inactivation in the liver may
      explain the improved safety profile and prolonged anti-inflammatory activity of
      ciclesonide.

PMID- 16566063
TI  - Michiko Tada (1938-2005).

PMID- 16566064
TI  - Bird flu fears widen.

PMID- 16566065
TI  - New insights into coral reef threats.

PMID- 16566066
TI  - Q & A: an interview with Patrick Lemaire.

PMID- 16566067
TI  - John Arthur Luetscher, Jr (1903-2005).

PMID- 16566068
TI  - Healthy eating. A sign of spring. Veggies that welcome in warm weather.

PMID- 16566069
TI  - Exchange lists. A way to plan meals.

PMID- 16566070
TI  - Diabetes & the uninsured: a national crisis.

PMID- 16566071
TI  - Pass the potatoes.

PMID- 16566073
TI  - Health tips. Soothing a sore throat.

PMID- 16566072
TI  - Chronic cough. It can be helped.

PMID- 16566074
TI  - Breast cancer drug offers dramatic results for some.

PMID- 16566075
TI  - Food advertising. Separating fact from fiction.

PMID- 16566076
TI  - Rosacea. A manageable condition.

PMID- 16566077
TI  - Why do my cheeks flush when I drink wine? I like a glass of wine with my evening
      meal, but I don't like having a red face.

PMID- 16566078
TI  - Low-grade gliomas: the debate continues.
AB  - Low-grade gliomas (LGG) are a heterogeneous group of tumors that tend to occur
      primarily in young adults and children. They are indolent, progressive, and often
      undergo anaplastic transformation. The prognosis of these tumors is primarily
      affected by age and pathologic type. Many questions remain in the management of
      LGGs, including the role of surgical resection (ie, maximal tumor resection), the
      optimal timing of radiation (ie, postoperative vs at the time of tumor
      progression), and the role of chemotherapy (ie, salvage after radiotherapy,
      primary treatment after surgery, concurrent with radiotherapy). Further
      complicating treatment decisions are concerns about toxicity with any
      intervention because LGG patients can often lead a relatively normal existence
      for years with no intervention. In this article we review the pertinent LGG
      literature published over the past few years and its impact on the management of
      LGGs.

PMID- 16566079
TI  - A growing hole in the safety net: physician charity care declines again.
AB  - Continuing a decade-long trend, the proportion of U.S. physicians providing
      charity care dropped to 68 percent in 2004-05 from 76 percent in 1996-97,
      according to a national study from the Center for Studying Health System Change
      (HSC). The ongoing decline in physician charity care is alarming given the
      increase in the number of uninsured people, particularly during the first half of
      the decade. Declines in charity care were observed across most major specialties,
      practice types, practice income levels and geographic regions. Increasing
      financial pressures and changes in practice arrangements may account in part for
      the continuing decrease in physician charity care.

PMID- 16566080
TI  - Low rates of nasal colonization with methicillin-resistant Staphylococcus aureus
      among staff members of an Italian hospital.

PMID- 16566081
TI  - Treatment of Hypertension in patients with type-2 diabetes mellitus.

PMID- 16566082
TI  - Prognostic staging of extensively pretreated patients with advanced HIV-1
      disease.
AB  - PURPOSE: Determinants of therapeutic success are poorly characterized in patients
      with extensive HAART experience. Positive prognostic factors (PPFs) in the TORO
      trials could serve as the basis for a prognostically meaningful staging of
      treatment-experienced patients initiating a new antiretroviral regimen. METHOD:
      In TORO, triple-class-experienced patients with viral load (VL) > or = 5,000
      copies/mL received an optimized background regimen of 3-5 antiretrovirals (based
      on treatment history and baseline resistance testing) +/- enfuvirtide (n = 995).
      Clinically relevant baseline PPFs that were predictive of 48-week virologic
      outcomes were identified via multiple regression analyses. RESULTS: The
      likelihood of VL < 400 copies/mL at 48 weeks (ITT analysis) was greater for those
      patients who had baseline CD4 count > or = 100 cells/mm3 (odds ratio [OR] 2.1;
      95% confidence intervals [CIs] 1.5, 3.1); baseline VL < 5 log10 copies/mL (OR
      1.8; 95% CIs 1.2, 2.6); received < or = 10 prior antiretrovirals (OR 2.4; 95% CIs
      1.6, 3.4); or received > or = 2 active antiretrovirals in their background
      treatment regimen (OR 2.3; 95% CIs 1.6, 3.3). Overall, 67% of triple-class
      experienced patients who met all four prognostic criteria and received
      enfuvirtide achieved VL < 400 copies/mL at 48 weeks vs. 43% for non-enfuvirtide
      patients (p < .05). Similar results were obtained when the analysis was done
      separately in each of the randomization arms of the study. CONCLUSION: Our
      findings provide guidance for physicians on expected outcomes in treatment
      experienced patients and should be of value in their clinical management, as well
      as in stratifying participants in clinical trials involving treatment-experienced
      patients.

PMID- 16566083
TI  - Simplicity and efficacy of a once-daily antiretroviral regimen with didanosine,
      lamivudine, and efavirenz in naive patients: the VESD study.
AB  - PURPOSE: Our aim was to analyze the efficacy and safety of didanosine-lamivudine
      efavirenz in a cohort of HIV patients starting antiretroviral therapy between
      January and September 2003. METHOD: We undertook a prospective, open-label,
      observational, multicenter study. RESULTS: 163 patients were enrolled. Over a 48
      week period, plasma HIV RNA levels declined sharply, with a median decrease at
      the end of the observation time of >4.62 log copies/mL. The proportion of
      patients achieving a plasma HIV RNA level below 50 copies/mL was 62.9% (intention
      to-treat analysis) at the end of the study period. The mean CD4 cell count
      increased steadily over time by 199 cells/microL. Antiviral efficacy was similar
      in patients with a baseline HIV RNA level above or below 100,000 copies/mL.
      Overall, 57 (34.1%) patients interrupted therapy; 9 due to lack of treatment
      response, 18 due to adverse side-effects, and 30 patients lost to follow-up or
      who withdrew their consent. Adherence was very high (90%-95%) and quality of life
      was good or very good in 69%. CONCLUSION: The once-daily combination of
      didanosine-lamivudine-efavirenz resulted in sustained viral suppression and was
      well-accepted by patients under real-life conditions, even immunosuppressed
      patients and those with a high viral load. Associated adverse events and
      virological failures were few.

PMID- 16566084
TI  - Long-term effect of acetyl-L-carnitine for antiretroviral toxic neuropathy.
AB  - BACKGROUND: Nucleoside analogue reverse transcriptase inhibitors (NRTIs) used for
      the treatment of HIV can a cause distal symmetrical peripheral polyneuropathy by
      disruption of mitochondrial metabolism. Treatment with acetyl-L-carnitine (ALCAR)
      has shown short-term symptomatic and histological improvement. Long-term effects
      have not been investigated. PURPOSE: To assess the subjective and objective
      degree of antiretroviral toxic neuropathy (ATN) during treatment with ALCAR.
      METHOD: A cohort of 21 patients with ATN who commenced treatment with ALCAR
      between March 1999 and October 2001 was reviewed after a mean of 4.3 years using
      standardized questionnaires and neurological examination. RESULTS: Of the 21
      patients, 2 had died and 3 were lost to follow-up. 16 patients were assessed. 10
      were still on potentially neurotoxic drugs. 13 were still taking ALCAR. 9 were
      pain free. The most common symptom was numbness (mild, moderate, and severe in
      12, 3, and 0 patients, respectively), followed by paraesthesia (8, 2, 2), pain
      (4, 3, 0), and burning (5, 2, 0). There was mildly reduced sensation in the toes
      of 8 patients. 13 patients reported that ALCAR had improved their symptoms very
      much or moderately, 2 reported no change, and 1 reported a moderate worsening.
      CONCLUSION: ALCAR led to long-term symptomatic improvement in most patients
      without the need to discontinue neurotoxic drugs. Although in this study there
      was no control group, this agent appears to be an effective pathogenesis-based
      treatment for ATN.

PMID- 16566085
TI  - Improving oral health with dental colleagues.

PMID- 16566086
TI  - En bloc resection of primary melanoma with regional lymph node dissection.
AB  - En bloc resection of the primary melanoma with the regional lymph node drainage
      basin as a method of controlling disease within the area was used in 281 patients
      with stage I or II melanoma arising on the extremities (proximal to wrist or
      ankle) or on the trunk from 1954 through 1964. The en bloc operation was
      performed in 212 patients with a five-year cure of 73.5% (156 of 212). Seventy
      six percent had histologically negative nodes. Only 2% developed regional
      recurrence. Sixty-nine patients had a discontinuous dissection. The five-year
      cure was comparable: 68% (47 of 69). The incidence of histologically negative
      nodes was similar (77%), but the regional recurrence rate was 14%. This
      difference is significant at P < .01. The incontinuity or en bloc procedure
      appears highly effective for its designed purpose.

PMID- 16566087
TI  - Appendicitis. A critical review of diagnosis and treatment in 1,000 cases.
AB  - One thousand cases of appendicitis seen from 1963 to 1973 were reviewed. The
      overall negative appendectomy rate was 20%, but in women between ages 20 and 40
      it exceeded 40%. Two thirds of the negative appendectomies were due to
      nonsurgical lesions. Mesenteric adenitis, gastroenteritis, and abdominal pain of
      unknown cause accounted for one third of the errors in females and two thirds in
      males. These diseases were best distinguished from appendicitis on the basis of
      temperature and white blood cell count. The remainder of the errors in females
      were due to pelvic inflammatory disease or other gynecologic diagnosis and were
      best distinguished from appendicitis on the basis of history and physical
      findings. The rate of perforation was 21% overall. The incidence of wound
      infection was 8.5%. Use of systemic antibiotics did not affect the wound
      infection rate.

PMID- 16566088
TI  - Screening for new metabolites from marine microorganisms.
AB  - This article gives an overview of current analysis techniques for the screening
      and the activity analysis of metabolites from marine (micro)organisms. The
      sequencing of marine genomes and the techniques of functional genomics (including
      transcriptome, proteome, and metabolome analyses) open up new possibilities for
      the screening of new metabolites of biotechnological interest. Although the
      sequencing of microbial marine genomes has been somewhat limited to date,
      selected genome sequences of marine bacteria and algae have already been
      published. This report summarizes the application of the techniques of functional
      genomics, such as transcriptome analysis in combination with high-resolution two
      dimensional polyacrylamide gelelectrophoresis and mass spectrometry, for the
      screening for bioactive compounds of marine microorganisms. Furthermore, the
      target analysis of antimicrobial compounds by proteome or transcriptome analysis
      of bacterial model systems is described. Recent high-throughput screening
      techniques are explained. Finally, new approaches for the screening of
      metabolites from marine microorganisms are discussed.

PMID- 16566089
TI  - Fatty acids from lipids of marine organisms: molecular biodiversity, roles as
      biomarkers, biologically active compounds, and economical aspects.
AB  - Because of their characteristic living environments, marine organisms produce a
      variety of lipids. Fatty acids constitute the essential part of triglycerides and
      wax esters, which are the major components of fats and oils. Nevertheless,
      phospholipids and glycolipids have considerable importance and will be taken into
      account, especially the latter compounds that excite increasing interest
      regarding their promising biological activities. Thus, in addition to the major
      polyunsaturated fatty acids (PUFA) such as eicosapentaenoic (EPA) and
      docosahexaenoic (DHA) acids, a great number of various fatty acids occur in
      marine organisms, e.g. saturated, mono- and diunsaturated, branched, halogenated,
      hydroxylated, methoxylated, non-methylene-interrupted. Various unprecedented
      chemical structures of fatty acids, and lipid-containing fatty acids, have
      recently been discovered, especially from the most primitive animals such as
      sponges and gorgonians. This review of marine lipidology deals with recent
      advances in the field of fatty acids since the end of the 1990s. Different
      approaches will be followed, mainly developing biomarkers of trophic chains in
      marine ecosystems and of chemotaxonomic interest, reporting new structures,
      especially those with biological activities or biosynthetic interest. An
      important part of this review will be devoted to the major PUFA, their relevance
      to health and nutrition, their biosynthesis, their sources (usual and promising)
      and market.

PMID- 16566090
TI  - Fish and shellfish upgrading, traceability.
AB  - Recognition of the limited biological resources and the increasing environmental
      pollution has emphasised the need for better utilisation of by-products from the
      fisheries. Currently, the seafood industry is dependent on the processing of the
      few selected fish and shellfish species that are highly popular with consumers
      but, from economic and nutritional points of view, it is essential to utilise the
      entire catch. In this review, we will focus on recent developments and
      innovations in the field of underutilised marine species and marine by-product
      upgrading and, more precisely, on two aspects of the bioconversion of wastes from
      marine organisms, i.e. extraction of enzymes and preparation of protein
      hydrolysates. We will deal with the question of accurate determination of fish
      species at the various steps of processing. Methods of genetic identification
      applicable to fresh fish samples and to derived products will be described.

PMID- 16566091
TI  - Marine microalgae.
AB  - Marine microalgae, the largest primary biomass, have been attracting attention as
      resources for new metabolites and biotechnologically useful genes. The
      diversified marine environment harbors a large variety of microalgae. In this
      paper, the biotechnological aspects and fundamental characteristics of marine
      microalgae are reviewed.

PMID- 16566092
TI  - Marine enzymes.
AB  - Marine enzyme biotechnology can offer novel biocatalysts with properties like
      high salt tolerance, hyperthermostability, barophilicity, cold adaptivity, and
      ease in large-scale cultivation. This review deals with the research and
      development work done on the occurrence, molecular biology, and bioprocessing of
      marine enzymes during the last decade. Exotic locations have been accessed for
      the search of novel enzymes. Scientists have isolated proteases and carbohydrases
      from deep sea hydrothermal vents. Cold active metabolic enzymes from
      psychrophilic marine microorganisms have received considerable research
      attention. Marine symbiont microorganisms growing in association with animals and
      plants were shown to produce enzymes of commercial interest. Microorganisms
      isolated from sediment and seawater have been the most widely studied, proteases,
      carbohydrases, and peroxidases being noteworthy. Enzymes from marine animals and
      plants were primarily studied for their metabolic roles, though proteases and
      peroxidases have found industrial applications. Novel techniques in molecular
      biology applied to assess the diversity of chitinases, nitrate, nitrite, ammonia
      metabolizing, and pollutant-degrading enzymes are discussed. Genes encoding
      chitinases, proteases, and carbohydrases from microbial and animal sources have
      been cloned and characterized. Research on the bioprocessing of marine-derived
      enzymes, however, has been scanty, focusing mainly on the application of solid
      state fermentation to the production of enzymes from microbial sources.

PMID- 16566093
TI  - Extreme environments as a resource for microorganisms and novel biocatalysts.
AB  - The steady increase in the number of newly isolated extremophilic microorganisms
      and the discovery of their enzymes by academic and industrial institutions
      underlines the enormous potential of extremophiles for application in future
      biotechnological processes. Enzymes from extremophilic microorganisms offer
      versatile tools for sustainable developments in a variety of industrial
      application as they show important environmental benefits due to their
      biodegradability, specific stability under extreme conditions, improved use of
      raw materials and decreased amount of waste products. Although major advances
      have been made in the last decade, our knowledge of the physiology, metabolism,
      enzymology and genetics of this fascinating group of extremophilic microorganisms
      and their related enzymes is still limited. In-depth information on the molecular
      properties of the enzymes and their genes, however, has to be obtained to analyze
      the structure and function of proteins that are catalytically active around the
      boiling and freezing points of water and extremes of pH. New techniques, such as
      genomics, metanogenomics, DNA evolution and gene shuffling, will lead to the
      production of enzymes that are highly specific for countless industrial
      applications. Due to the unusual properties of enzymes from extremophiles, they
      are expected to optimize already existing processes or even develop new
      sustainable technologies.

PMID- 16566094
TI  - [Resuscitation: new guidelines with incisive changes. A question of survival].

PMID- 16566095
TI  - ["Everything will be easier" (interview by Jochen Aumiller)].

PMID- 16566096
TI  - [Do you recognize tuberculosis?].

PMID- 16566097
TI  - [The intestine as erroneous suspect of illness].

PMID- 16566098
TI  - [Your patients swallow fewer pills than you think].

PMID- 16566099
TI  - [When must the tonsils be removed? (interview by Dr. Thomas Meissner)].

PMID- 16566100
TI  - [Identification and treatment of personality disorders in the physician's
      office].

PMID- 16566101
TI  - [Anxious (avoidant) personality disorder].
AB  - The anxious (avoidant or fearful) type of personality disorder has a lifetime
      prevalence of 5%, which makes it the most common form of personality disorder.
      Although it is one of the leading risk factors for severe depressive illnesses,
      anxiety disorders, substance dependence, eating disorders and chronic pain, its
      importance is frequently underestimated. Ambulatory treatment comprises
      psychoeducation, self-management and training in social competence.

PMID- 16566102
TI  - [Schizotypal personality disorder--diagnosis and treatment].
AB  - Schizotypal personality disorder is relatively common disorder, and is considered
      to be a mild form of schizophrenia. It is characterized by such "psychotic"
      symptoms as ideas of reference, odd or magical thinking, perceptual illusions and
      an inappropriate or flattened affect. In their contact with others, patients show
      odd expression and behavior. Since, numerous schizotypal symptoms can be treated
      successfully with atypical antipsychotic medication, the patient should be
      referred to a psychiatrist or neurologist. The mainstay of psychotherapy consists
      in crisis management, development of self-awareness of the problem, breaking down
      social isolation and general unspecific support in coping with daily problems.

PMID- 16566103
TI  - [Nacissistic personality disorder].
AB  - The narcissistic personality disorder is the extreme form of the so-called
      narcissistic personality style, which is characterized by exaggerated self
      importance coupled with an inordinate desire to be admired, ideas of grandiosity
      and a strong sense of entitlement, an absence of empathy and feelings of envy. In
      contact with others, the narcissist appears arrogant, readily feels injured, and
      takes advantage of other to achieve his own ends. A central psychodynamic role in
      the development of the condition is a labile sense of self-worth and its
      overcompensation. Psychotherapeutic treatment aims initially to develop an
      awareness of the problem in the patient, correction of cognitive dysfunction and
      a reduction in aggressive or disdainful behavior. Impulsive and aggressive
      behavior and attacks of depression may be reduced through the use of selective
      serotonin reuptake inhibitors.

PMID- 16566104
TI  - [Borderline personality disorder].
AB  - Characteristics of a borderline personality disorder include emotional
      instability and a self-threatening lack of impulsive control. As a result,
      interpersonal relationships are rendered difficult. The central elements of
      treatment are psychoeducation, self-management, improved stress tolerance and
      awareness, emotion managment and training in social competence.

PMID- 16566105
TI  - [What's to be done when a cough will not clear?].

PMID- 16566106
TI  - [No physician is safe from the state attorney].

PMID- 16566107
TI  - [Bankruptcy attorney reports about increasing workload. Number of bankrupt
      medical practices increases].

PMID- 16566108
TI  - [Shoulder dislocation: Do you know the maneuvers to reposition the shoulder?].

PMID- 16566109
TI  - [At least she was restrained by seat belts].

PMID- 16566110
TI  - [Image of the month. Spontaneous pneumomediastinum].

PMID- 16566111
TI  - [Clinical case of the month. Popliteal artery entrapment syndrome: a cause of non
      atherosclerotic arteriopathy in a young patient].
AB  - Popliteal artery entrapment syndrome is one of the most frequent causes of non
      atheromatous arteriopathy among young people without any vascular risk factor.
      The physiopathology is an extrinsic compression of the artery by muscular
      structures. It is important to make the right diagnosis because surgery is the
      only treatment.

PMID- 16566112
TI  - [Chronic intestinal angina and bypass revascularization: a case report].
AB  - Intestinal angina is a rare affection with a high morbidity-mortality rate if not
      diagnosed. It is characterized by abdominal pain and postprandial vomiting,
      weight loss and anorexia. Arteriography allows confirmation of the diagnosis. The
      following case is a typical example of its clinical presentation and surgical
      treatment. Different techniques of revascularisation in case of a stenosis of the
      main digestive arteries are discussed.

PMID- 16566113
TI  - [Secondary cancers in childhood].
AB  - Improved survival of pediatric cancer patients will lead to an increase of late
      sequellae such as secondary malignant neoplasms (SMN). Specific pediatric factors
      predisposing to these SMN are as follows: long expecting duration of life, high
      cellular proliferative potential, toxicity of often combined cancer therapies
      (radio- and chemotherapies) and more frequent genetic predisposition to cancer.
      Better understanding of these factors could improve patients management and could
      lead to the development of less toxic future therapies with the hope to decrease
      the risk of SMN.

PMID- 16566114
TI  - [Asthma and tobacco].
AB  - Roughly 40% of asthmatics are or have been smokers. These smoking asthmatics have
      been largely overlooked in the past. Tobacco is today considered as a risk factor
      for asthma and it seems that smoking asthmatics exhibit a different phenotype as
      compared to non smoking asthmatics. The inflammatory substrate differs widely,
      not only with respect to the type of cells present in the airways, but also with
      respect to the mediators brought into play. On the clinical point of view the
      asthma of smokers is also more severe that in non smokers, both at the
      symptomatic and the functional level. The asthma severity in smokers is partly
      linked to a resistance to inhaled corticoids, the cornerstone of maintenance
      treatment in asthma. This makes urgent to assess alternative treatment to inhaled
      corticoids for this asthma phenotype, but also emphasizes the need to support
      smoking cessation in asthmatics.

PMID- 16566115
TI  - [Hydrocephalus in children].
AB  - The files of all young patients, aged from one day to 17 years, that were
      operated for hydrocephalus in the Service of Neurosurgery of the Citadelle
      Hospital from 1987 to 2003 were reviewed and analysed. Over these 16 years of
      practice, a shunt was placed in a total of 194 children. This paper is mainly
      concerned with the etiologies of hydrocephalus and the complications related to
      the surgical procedure.

PMID- 16566116
TI  - [Kyphoplasty for the treatment of painful vertebral hemangioma].
AB  - Vertebral angiomas are frequent and often asymptomatic. Sometimes although they
      do not seem invasive radiologically, they are responsible for local pain. If
      there is concordance between pain and vertebral angioma localisation, surgery
      such as vertebroplasty or cyphoplasty can be proposed. These techniques lead to a
      quick and complete removal of symptoms.

PMID- 16566117
TI  - [Partial breast irradiation: the role of brachytherapy. A new treatment option
      for early breast cancer].
AB  - Early breast cancer can be treated by conservative surgery followed by partial
      breast irradiation. This recent treatment replaces classical external beam whole
      breast radiotherapy. Several techniques are available but most experience does
      exist with interstitial catheter based brachytherapy. This well tolerated
      treatment shortens the treatment time and offers a good local control and
      cosmetic outcome, comparable to the best classical treatments, as confirmed by
      the first published results. These good results can only be obtained by rigorous
      patient selection and very precise 3D imaging and source implantation techniques.

PMID- 16566118
TI  - [Cutaneous signs of endocrinopathies].
AB  - Some cutaneous lesions accompany or reveal endocrine disorders. Identifying the
      endocrinopathy is very important because it sometimes allows corrective rather
      than symptomatic treatment. The most frequenly involved diseases include
      thyrotoxicosis, hypothyroidism, the auto-immune disorders of thyroid, Cushing
      syndrome, Addison disease, acromegaly, androgen-dependent disorders,
      hypopituitarism, hypoparathyroidism, pseudohypoparathyroidism and diabetes
      mellitus.

PMID- 16566119
TI  - [Value of aerobic rehabilitation in the management of fibromyalgia].
AB  - This study assesses the influence of a muscular aerobic revalidation program on
      the management of the fibromyalgia syndrome. After 3 months, benefits consisting
      of increased muscle performances associated with a reduction of pain and an
      improvement of quality of life were documented. This study confirms the value of
      aerobic muscle exercise in fibromyalgia patients.

PMID- 16566120
TI  - [Carotid angioplasty and stenting: a justified therapeutic alternative?].
AB  - The efficacy and safety of carotid endarterectomy in the prevention of stroke,
      demonstrated in 1991, has elevated it to the treatment of choice for the
      extracranial carotid occlusive disease. The recent advances in endovascular
      treatment created an enthusiasm for carotid angioplasty and stenting (CAS) which
      is increasingly becoming an alternative to endarterectomy in high risk patients
      and more recently for the NASCET-eligible and asymptomatic patients with
      significant atherosclerosis. Although, the results of CAS must be at least
      equivalent, in terms of safety, efficacy, stroke prevention on the long term, to
      the published trials (NASCET, ECST, ACAS) in order to justify any change in the
      gold standard in the treatment of carotid bifurcation disease, which remain
      carotid endarterectomy.

PMID- 16566121
TI  - [Delivery outcome of adolescents in Far North Cameroon].
AB  - Delivery in teenager is associated with increased risk. The aim of this study was
      to evaluate the contribution of teenagers (10-19 years or less) to the total
      number of deliveries over a 10 year period in the Maroua provincial hospital
      (Cameroon) This was a retrospective study. The deliveries of 3.328 teenagers were
      analysed as far as their contribution to the deliveries is concerned and how this
      contribution changed with time from 01/01/1995 to 31/12/2004 at the Provincial
      Hospital Maroua (Cameroon). Analyses were performed using Excel and Epi Info 6.
      The chietaiota2 tests of the tendency, taking in account all ten age groups, was
      used to appreciate the phenomenon over time. This trend was considered
      significant if p<0.05. RESULTS: During the study period 13.026 women delivered,
      489 cases were excluded because the age was not specified. Finally, 3.328
      teenagers were analysed out of a total of 12537 cases, as far as their
      contribution to the number of deliveries from 1995 to 2004 in the Maroua
      provincial hospital. Teenagers contributed for 26,54% of total deliveries in
      Maroua Provincial Hospital, (Cameroon). Teenagers of 16 and less contributed for
      7,58%, and those aged 17 to 19 years contributed for 18,25%. We found out that
      the trend over the study period, has not changed (p>0.05). This study emphasizes
      the need of redynamisation of adolescents health services in Extreme North
      Cameroon. Studies should be done to determine the impact of young age on the
      delivery outcome.

PMID- 16566122
TI  - [Hydrocortisone 17-butyrate (Locoid), a thirty-year ongoing innovative drug].
AB  - Since half a century, dermocorticoids represent worthy compounds in
      dermatological therapy. About thirty years ago, hydrocortisone 17-butyrate was
      introduced on the Belgian market. This compound combines good efficiency and
      reduced risk of side effects. Its topical formulations have been enriched over
      time. The original Locoid lipocream and Locoid Crelo presentations confer
      remarkable qualities to the product. We report a synopsis of clinical and
      translational studies devoted to this unique dermocorticoid.

PMID- 16566123
TI  - [Iron metabolism in the yeast].
AB  - Current data concerning transport, storage and utilization of iron in the yeast
      cells, particularly Saccharomyces cerevisiae are summarized in the paper. It has
      been marked that iron uptake in the cells provides by high affinity system, it
      function is carried out by protein complex Fet3-Ftr1, and Fet4, protein with low
      affinity to iron ion. The both systems utilize Fe(II). Furthermore, the active
      site of the protein Fre1 is exposed on the outer side of plasmalemma. This
      protein, due to ferrireductase activity, provides availability of Fe(III) to the
      cell. The information regards to participation of siderophores and metal-proton
      plasma membrane exchangers Smf1 in iron transport is brought. Particular
      attention is given to regulation of expression of the genes, coding the iron
      metabolic systems. Some aspects of iron utilization for Fe-S-containing enzymes
      synthesis are lighted. It has been concluded that the yeast is a perspective
      subject for studying balance of living organisms between iron essentiality and
      its ability to trigger free radical reactions.

PMID- 16566124
TI  - [Alpha-lipoic--dihydrolipoic acids--active bioantioxidant and bioregulatory
      system].
AB  - alpha-Lipoic (LA) acid (thioctic acid) is an intramolecular disulfide that may be
      simply endogenically turned into dithiol. Dihydrolipoic acid (DHLA)/ LA and DHLA
      are bioantioxidants. They are synthesized in the body and taken with diet. Water-
      and lipide-soluble LA is highly-effective against the reactive oxygen species. LA
      (DHLA) protect the biomembranes, mitochondria from oxidative stresses of various
      kinds. LA, DHLA and lipoamide function as cofactors of polyenzyme mitochondrial
      complexes of 2-oxoacid dehydrogenases, of glycin decarboxylases and of some other
      enzymes. LA (DHLA) is ubiquinone reactivator and synergist by vitamin A, C, E. LA
      optimizes glucose metabolism, it is effective in insulin-resistant diabetes and
      its complications, in neutopathies and neurodegenerative diseases.

PMID- 16566125
TI  - [Modulation of molecular signaling mechanisms in excitable cells by toxins and
      bacterial substances].
AB  - The mechanisms of bacterial substances (protein A, peptidoglican Staphylococcus
      aureus), bacterium toxins (St. aureus, Corynebacterium diphtheriae, Shigella
      dysenteriae, Clostridium botulinum, Clostridium tetani, Vibrio choleral),
      transfer factor of immune reactivity to Staphylococcus aureus upon the key link
      (acetylcholine-, ATP-, inositol-1,4,5-triphosphate-, ryanodin-sensitive
      receptors, G-proteins, Ca2+, K(+)-transporting systems, second messengers) in the
      chain of signal conduction of excitatory and inhibitory agonists in excitable
      cells were examined. The action of these immune-active substances upon
      contractile proteins ATP-ase activity and protein synthesis was also discussed.

PMID- 16566126
TI  - The effect of buthionine sulfoximine on the glutathione level in goldfish
      tissues.
AB  - This study describes the effect of DL-buthionine-[S,R]-sulfoximine (BSO) on the
      glutathione equivalents (GSH-eq = GSH + 2 GSSG) of goldfish. BSO causes depletion
      of cellular GSH by inhibiting gamma-glutamylcysteine synthetase, a key enzyme of
      the GSH biosynthesis pathway. BSO at 1,000 and 1,500 mg/kg was effective in
      promoting 50 and 80% depletion of GSH-eq from brain and liver, respectively,
      within 3 days. Lower doses of BSO failed to effectively promote hepatic GSH-eq
      depletion. Moreover, no evident toxic side-effects were observed (including
      hepatic lipid peroxidation and free radical-mediated oxidation of proteins) in
      goldfish in response to BSO intraperitoneal injections. We conclude that BSO can
      be used to deplete GSH-eq in goldfish liver and brain, but attention should be
      paid to species-specific variations in BSO effects.

PMID- 16566127
TI  - [Effect of proteasomal proteolysis on NO-synthase activity in isolated
      platelets].
AB  - In experiments with isolated platelets it was shown, that application of
      proteasomal fraction II (PF II) from rabbit's reticulocytes changes the activity
      of endothelial nitric oxide synthase (eNOS). During incubation of sonicated
      platelets with PF II eNOS activity increased by 24.6% (p = 0.02). Methylated
      ubiquitin and clasto-lactacystin beta-lacton significantly eliminated this
      effect. So, it is not eNOS that is subsequent to proteasomal degradation, but a
      certain negative regulator of its activity. eNOS activity in platelets, treated
      with H2O2 (1 mM), after incubation with PF II increased to a higer extent, and
      was 3.4 +/- 0.36 UF/min x 10(6) cells (for 51.3% more, than in control), but H2O2
      did not affect the activity of enzyme in platelets under analogous condition
      without addition of PF II. It was established, that eNOS activity decreases after
      60 min of incubation with 10 mM of clasto-lactacystin beta-lacton by 11.6%, and
      with 20 mM--by 28.6% (p < 0.05). Data obtained witnesses about participation of
      ubiquitin-dependent proteasomal proteolysis in regulation of eNOS activity and
      possibility of the effect upon intensity of NO production due to acceleration of
      degradation of intracellular regulators of this enzyme's activity.

PMID- 16566128
TI  - [Variance analysis of Cd2+, Zn2+, and Mn2+ effect on membrane Na+,K(+)-ATPase
      activity of loach embryos].
AB  - The evaluation of influences Cd2+, Zn2+, Mn2+ in concentrations 10(-6), 10(-5),
      10(-4) M (factor of dose) on the Na+, K(+)-ATP-ase activity in the early period
      of development (60-330 min.) of loach embryos (time factor) using one- and two
      factor analysis of variance has been performed. It has been detected, that the
      changes of enzyme activity are mainly caused by action of the explored cations
      and do not depend on time of embryos development. The most influence on activity
      in the indicated period of embryos development of loach renders Cd2+ in
      concentration 10(-4) M, relative value of its influence being 95.7% (p = 0.01).
      Substantial concentration dependence of the Na+, K(+)-ATP-ase activity is exposed
      to the action of each of cations. The values of the influence of their
      concentration changes during the studied period of development differ
      insignificantly for all cations and make 76.2-77.5% (p < 0.01).

PMID- 16566129
TI  - [Protein kinase activity of immunoglobulins in human blood plasma].
AB  - Protein kinase activity of the immunoglobulins (Ig) fractions from blood plasma
      of clinically healthy humans has been studied. IgA, IgG and IgM preparations have
      been obtained using column chromatography on sorbents with rabbit antibody to H
      chains of human Ig. The level of 32P incorporation in casein in the presence of
      [gamma-32P]ATP was used to determine protein kinase activity of the Ig-fractions.
      The protein kinase activity of the preparation of IgA (but not IgG or IgM) was
      defined. The high-purified preparation of IgA for studing the protein kinase
      activity has been obtained. Three stages of purifications were used--the
      separation of plasma proteins by polyethylenglycol 6000, gel-filtration on the
      column with Toyopearl HW-60 Fine and affinity chromatography on the column
      containing rabbit antibody to H-chains of human IgA. It was revealed that the
      fraction of IgA possesses the casein phosphorylation activity. Heparin and
      trifluoperazine completely and partially inhibited protein kinase activity of IgA
      while spermidine did not render essential influence. On the basis of the obtained
      results the conclusion is made that the blood of clinical by healthy humans
      contains IgA possessing the protein kinase activity.

PMID- 16566130
TI  - [Effect of nitric oxide on 5'-nucleotidase activity of the membrane rafts in the
      smooth muscle cells].
AB  - We investigated the effect of nitric oxide on the catalytic activity of 5'
      nucleotidase associated with insoluble membrane domains (rafts) of pig stomach
      smooth muscle. The low concentration (0.1-10.0 microM) of nitric oxide donor
      sodium nitroprusside led to essential increase of catalytic activity of 5'
      nucleotidase. Maximal increase was observed at concentration of sodium
      nitroprusside of 1 microM. The enzyme's catalytic activity decreased to about
      control value at higher concentration of this substance. The catalytic activity
      of 5'-nucleotidase was also increased at presence of NaNO2, but only at high
      concentration (10 mM). The specific thiol-alkylating agent N-ethylmaleinimide (1
      100 microM) led to essential decrease of enzyme catalytic activity. Our data
      shows that nitric oxide changes the AMP-ase activity of 5'-nucleotidase, that is
      thought to be due to direct effect of this substance on protein. We suppose, that
      such effect of nitric oxide could be physiologicaly important in functioning of
      smooth muscle.

PMID- 16566131
TI  - [Modulating effect of glutamate transporter inhibitors on accumulation and
      release of the neuromediator by the brain nerve terminals in rats].
AB  - L-[14C]glutamate uptake and release processes in nerve terminals has been
      investigated using the nontransportable and transportable competitive inhibitors
      of glutamate transport as tools. The effects of DL-threo-beta-benzyloxyaspartate
      (DL-TBOA) and DL-threo-beta-hydroxyaspartate (DL-THA) on the accumulation of L
      [14C]glutamate have been evaluated after the exposure of rats to centrifuge
      induced hypergravity. Both analogs potently inhibited the L-[14C]glutamate uptake
      in a dose-dependent manner (100 microM glutamate, 30 s incubation period). The
      IC50 values for DL-TBOA calculated on the basis of curves of non-linear
      regression kinetic analysis was 18 +/- 2 microM and 11 +/- 2 microM (p < or =
      0.05) before and after the exposure to artificial gravity, respectively. L-THA,
      transportable analog, exhibited similar inhibitory characteristics (18 +/- 2 and
      12 +/- 2 microM, respectively). We have also demonstrated that DL-TBOA exerted
      slighter effect on depolarization-evoked carrier-mediated L-[14C]glutamate
      release in control rats in comparison with gravity-loaded ones. Thus, DL-TBOA had
      complex effect on glutamatergic transmission, inhibited uptake and release of L
      glutamate, and perhaps, became more potent under centrifuge-induced hypergravity.

PMID- 16566132
TI  - [Calcium release from the rat liver mitochondria during collapse of the membrane
      potential].
AB  - Ca(2+)-release from rat liver mitochondria after protonophore (carbonyl cyanide m
      chlorophenylhydrazone, CCCP)-induced membrane depolarisation is studied. It is
      shown that the release of calcium is accompanied by an increase of the inner
      mitochondrial membrane permeability as the result of the opening of permeability
      transition pore (PTP). Calcium is released from mitochondria through the
      uniporter working in reverse mode and also by PTP mechanism which accounts for
      ruthenium red (RR)-insensitive component of total. Ca(2+)-release. Unlike Ca2+,
      the strontium release from the mitochondria is completely sensitive to RR,
      specific uniporter blocker, which shows the absence of rapid Sr(2+)-efflux
      mechanisms other than uniporter of bivalent cations. The data obtained also give
      an evidence that the lifetime of the open state of the pore is limited, and
      barrier properties of the mitochondrial membrane are restored after the closure
      of the pore.

PMID- 16566133
TI  - [Kinetic model of spermine effect on the Mg2+, ATP-dependent transport of Ca ions
      in the smooth muscle mitochondria].
AB  - In experiments, carried out with the use of a radioactive label (45Ca2+) on
      suspension of rat uterus myocytes treated with digitonin solution (0.1 mg/ml),
      influence of spermine on the Mg2+, ATP-dependent Ca2+ transport in the
      mitochondria was investigated. Ca2+ accumulation in the mitochondria was tested
      as such which was blocked by ruthenium red (10 microM) and was not sensitive to
      thapsigargin (100 nM). It was shown, that dependence of initial speed of Ca ions
      accumulation in the mitochondria on spermine concentration (0.1-10 mm) is
      described by a bell-shaped curve. Spermine concentration being increased in the
      range of 0.1-1 mM the stimulation of Ca2+ accumulation was observed, at the
      further increase in polyamine concentration up to 10 mM the suppression of this
      process took place. On the basis of the analysis of the authors' experimental
      results and the literature data the model of complex spermine action on Ca2+
      accumulation in mitochondria was proposed and analyzed. The existence of two
      spermine binding sites on mitochondrial membrane--S1 and S2 occupation of which
      is connected to activation and inhibition of Ca(2+)-unipoter, accordingly, was
      taken into account. The kinetic analysis of the model which has been made in an
      equilibrium mode, allowed to calculate some important quantitative parameters
      describing spermine influence on Ca ions accumulation in mitochondria. It is
      supposed, that the proposed model can be useful in the further research of
      polyamine influence on transmembrane exchange of Ca ions in mitochondria.

PMID- 16566134
TI  - [Investigation of antioxidant activity of quinoline thioderivatives].
AB  - Antioxidant activity of new synthetic physiologically active substances
      (thioderivatives of quinoline) are investigated using the complex of primary
      estimation techniques in vitro and in vivo. It is shown that the compounds
      investigated display both antiradical and anti-oxidative activity, most strongly
      delineated for the compounds with methoxygroup in the 6th position of quinoline
      cycle. The suppositions concerning the mechanism of their antioxidant activity
      are made.

PMID- 16566135
TI  - [Purification and study of carbohydrate specificity of lectin from Sarcoscypha
      coccinea (Fr.) Lambette].
AB  - A lectin that revealed affinity for lactose, N-acethylactosamine, 4-nitrophenyl
      beta-D-gluco- and galactopyranosides from fruiting bodies of Sarcoscypha coccinea
      (Fr.) Lambette was purified by affinity chromatography on immobilized ovomucoid.
      According to electrophoresis data in 15% SDS-PAGE the lectin contains two very
      low-differing components with molecular weight 32 kDa. Molecular weight of the
      lectin is 128 kDa according to gel-chromatography on sephadex G-200. The lectin
      agglutinates rabbit erythrocytes and slightly weaker agglutinates human
      erythrocytes. After dialysis against 1% EDTA sodium salt solution the lectin
      loses hemaglutinating activity, but after the next dialysis against CaCl2
      solution it is restored.

PMID- 16566136
TI  - [Interrelation between thrombin structure and its stability].
AB  - Temperature inactivation of human thrombin has been studied when finding out the
      mechanism of this enzyme stabilization by amino acids. Effect of a number of
      amino acids on thrombin in the conditions (pH) of the highest activity of
      proteinase has been investigated. It is established that most amino acids are
      characterized to more or less extent by the protective action, when hampering the
      temperature inactivation of the enzyme. The correspondence was mainly found
      between the stabilizing effect of amino acids and thrombin specificity. Thrombin
      is stabilized by L-arginine and DL-lysine more intensively than by other amino
      acids. A stabilizing effect of L-glutamic acid was shown in contrast to the
      action of the latter on trypsin that was obviously connected with the original
      structure of the active centre of thrombin, that is the availability of anionic
      binding centre which includes Lys68, Arg72, Arg77. High thrombin stabilization by
      such amino acids as phenylalanine, DL-serine, DL-methonine was an exception. It
      was established that amino acids stabilize thrombin with formation of a compound
      with the reactive centre of its molecule, like the compounds enzyme-substrate.
      The macrostructure stability probably depends, to a considerable extent, on the
      state of the enzyme reactive centre: thrombin molecules, which contain a free
      reactive centre, are more labile than those which reactive centre is bound to the
      reagent of more or less specific character. The inhibition of the autolysis
      process may be another manifestation of thrombin stabilization by amino acids.

PMID- 16566137
TI  - [Effect of N-stearoylethanolamine on the level of stable NO metabolites in
      different pathological conditions which are accompanied by oxidative stress].
AB  - The effects of N-stearoylethanolamine (NSE) at the level of stable NO metabolites
      -NO2- NO3- under different pathological conditions which were accompanied by
      oxidative stress and NO disbalance were studied. It was found that NSE promoted
      the increasing of NO metabolites level on the animal models with deficit of NO
      compared to control and evoked decreasing content of NO2- and NO3- under
      pathological conditions with NO overproduction. It is suppoused, that NSE effects
      could be determined, by its ability to modulate the the activity of NO-synthase
      izoformes.

PMID- 16566138
TI  - [Effect of intermittent hypoxic hypoxia on energy supply of rat skeletal muscle
      during adaptation to physical load].
AB  - The experiment, on Wistar male rats was carried out to investigate influence of
      endurance training (swimming with load 7.0 +/- 1.3% body weight, 30 min a day,
      during 4 weeks) and additional intermittent hypoxic training (12% O2 in N2 - 15
      min, 21% O2 - 15 min, 5 sessions a day, during the first 2 weeks) on the
      following parameters: ADF-stimulated mitochondrial respiration, lactate/pyruvate
      ratio, succinate dehydrogenase activity, and lipid peroxidation in skeletal
      muscle. The next oxidation substrates were used: 1 mmol/l succinate and 1 mmol/l
      alpha-ketoglutarate as well as the next inhibitor succinate dehydrogenase 2
      mmol/l malonate. It was shown that physical work combined with intermittent
      hypoxic training led to the increase of mitochondrial respiration effectiveness
      in muscle energy supply under alpha-ketoglutarate oxidation in comparison with
      succinate oxidation as well as to the decrease of succinate dehydrogenase
      activity and lipid peroxidation. The study suggested that these changes may
      correct mitochondrial dysfunction under intensive muscular work.

PMID- 16566139
TI  - [Effect of tryptophan on mediator content in the brain tissue of rats with
      different levels of seizure susceptibility].
AB  - The effects of per orally administered tryptophan on serotonin and GABA levels in
      different brain areas were found to depend on initial levels of seizure
      susceptibility. Elimination of difference in the content of investigated mediator
      between animals with high and low seizure susceptibility was observed. Serotonin
      level was approximated to the initial one in rats with high seizure
      susceptibility but GABA level was approximated to the initial one in rats with
      low seizure susceptibility. Possible mechanismes of realization of tryptophan
      therapeutic effects are discussed.

PMID- 16566140
TI  - [Influence of conditions of artificial hibernation on energy metabolism indices
      in rats].
AB  - Influence of the conditions of artificial hibernation on the content of ATP, ADP,
      AMP, cAMF in the blood and liver of rats is studied. It is established, that the
      entering and stay of animals in the conditions of artificial hibernation is
      accompanied by a decrease of the content of ADP and P(l). The animal coming out
      of the condition of artificial hibernation is accompanied by an increase of the
      content of ATP and cAMP and achievement in twenty-four hours of the level of
      monitoring values.

PMID- 16566142
TI  - [Glycolipid changes in tissues of wheat leaves induced by exogenous hydrogen
      peroxide].
AB  - The results of the study of H2O2 treatment of wheat leaf glycolipid composition
      are presented. The fraction changes depended upon H2O2 concentration, way of
      treatment and exposition. The most typical reaction was galactolipid (MGDG, DGDG)
      content increase while lower sulpholipid variations at low doses of the root
      treatment and at leaf spraying.

PMID- 16566141
TI  - [Ability of lectins to model the action of antibiotics on growth of mutants of
      Bacillus subtilis].
AB  - Using the bacterium B. subtilis as a model and antibiotics as metabolic
      inhibitors which can suppress replication (mitomycin), transcription (rifampycin)
      or translation (streptomycin), it is shown that carbohydrate-binding proteins
      (lectins of plant origin) have different action on intracellular processes under
      study. The effect depends on lectin's structure and on the condition of bacterial
      reparation/recombination system. Lectins with chitin-binding domain (STA, WGA) is
      characterized by the most expressed effect on the repair-proficient strain when
      the inhibitor of template function of DNA (mitomycin C) was used. The absence of
      such effect on mutants recP and polC may prove that the corresponding bacterial
      proteins play the role of mediators in transmission of the signal influence of
      lectins. The representative of ribosome-inactivating lectins--SNA-I--could
      increase the streptomycin effect. It is proposed that intracellular effects of
      lectins have complex mechanisms which need participation of repair functions.

PMID- 16566143
TI  - A new enzymo-chemical method for simultaneous assay of methanol and formaldehyde.
AB  - A new enzymo-chemical method for the simultaneous assay of methanol and
      formaldehyde in mixtures is described which exploits alcohol oxidase (AO) and
      aldehyde-selective reagent, 3-methyl-2-benzothiazolinone hydrazone (MBTH). The
      enzyme is used for methanol oxidation to formaldehyde and MBTH plays a double
      role: 1) at the first step of reaction, it forms a colorless azine adduct with
      pre-existing and enzymatically formed formaldehyde and masks it from oxidation by
      AO; 2) at the second step of reaction, non-enzymatic oxidation of azine product
      to cyanine dye occurs in the presence of ferric ions in acid medium. Pre-existing
      formaldehyde content is assayed by colorimetric reaction with MBTH without
      treating samples by AO, and methanol content is determined by a gain in a colored
      product due to methanol-oxidising reaction. Possibility of differential assay of
      methanol and formaldehyde by the proposed method has been proved for model
      solutions as well as for real samples of industrial waste and technical
      formaline. A threshold sensitivity of the assay method for both analytes is near
      1 microM that responds to 30-32 ng analyte in 1 ml of reaction mixture and is 3.2
      fold higher when compared to the chemical method with the use of permanganate and
      chromotropic acid. Linearity of the calibration curve is reliable (p < 0.0001)
      and standard deviation for parallel measurements for real samples does not exceed
      7%. The proposed method, in contrast to the standard chemical approach, does not
      need the use of aggressive chemicals (concentrated sulfuric, phosphoric,
      chromotropic acids, permanganate), it is more simple in fulfillment and can be
      used for industrial wastes control and certification of formaline-contained
      stuffs.

PMID- 16566144
TI  - [Determination of the affinity of high- and low-affinity antibodies, which are in
      a mixture, using ELISA and the method of non-linear regression].
AB  - It was shown that application of the method of non-linear regression for the
      solution of the equation, which relates the fraction of free antibodies in a
      mixture and antigen concentrations, allows to determine the affinity constants
      for two antibodies in a mixture. Such method is easier and more accurate than the
      suggested by us earlier method, which use the numerical solution of the
      appropriate four equations, that describe the relations between the experimental
      data obtained by ELISA, competing antigen concentration, and values of antibody
      affinity. In addition, the proposed method allows using much less quantity of
      experimental measurements without diminishing of the accuracy for the affinity
      constants evaluations.

PMID- 16566145
TI  - Assessing risks of metals added to soils in Europe and North America.

PMID- 16566146
TI  - Labile zinc concentration and free copper ion activity in the rhizosphere of
      forest soils.
AB  - Water-soluble and acid-extractable Cu and Zn, water-soluble organic carbon
      (WSOC), pH, differential pulse anodic stripping voltammetry-labile Zn (ZnL), Zn2+
      activity (Windemere humic aqueous model [WHAM]; http://chess.ensmp.fr/
      chemsites.html), and Cu2+ activity with an ion-selective electrode were compared
      between the rhizosphere and the bulk components of nine acidic forest sites from
      southeastern Canada. At all sites, the WSOC contents were higher in the
      rhizosphere than in the bulk component. Acidity was also higher in the
      rhizosphere, although pH differences were significant at only five sites. The
      concentrations of Zn in water extracts and ZnL contents (at six sites) were
      higher in the rhizosphere, whereas acid-extractable Zn was only marginally
      increased in the rhizosphere. Calculations with WHAM indicated that free Zn2+ ion
      activities were higher in the rhizosphere than in the bulk soil but that the
      fraction of total dissolved Zn in water extracts that is present as free Zn2+ did
      not differ significantly between the two components. The concentration of Cu in
      the water extract was higher in the rhizosphere for all sites, but acid
      extractable Cu levels did not differ. The fraction of water-soluble Cu present as
      Cu2+ was higher in the bulk soil, although Cu2+ activities did not significantly
      vary with proximity to roots. These results showed that the processes acting in
      the rhizosphere of forest soils strongly affected the concentrations of dissolved
      Zn and Cu and that this microenvironment should be considered when estimating the
      bioavailability and the ecological risks of metals in soils.

PMID- 16566147
TI  - Assessment and control of the bioavailability of nickel in soils.
AB  - Nickel, a potentially toxic metal, is present in all soils with an average
      concentration of 20 to 30 mg/kg, sometimes exceeding 10,000 mg/kg (e.g.,
      ultramafic soils). The ecotoxicological risk of Ni in soils to organisms is
      controlled by its availability. It is therefore essential to identify an
      efficient and reliable method for the evaluation of this risk. This paper
      presents a complete study of the effect of Ni origin, localization, and soil
      properties on its availability as assessed with the isotopic exchange kinetics
      (IEK) method and compares plant response to isotopically exchangeable properties
      of Ni in soils. We performed IEK on 100 soil samples representing a worldwide
      range of Ni fate, and concentrations showed that pH was the main influencing
      parameter and that labile Ni (i.e., isotopically exchangeable Ni, Et) could be
      reasonably well assessed by a single diethylene triamine pentaacetic acid
      extraction. The identification of the soil mineral phases that bear Ni (bearing
      phases) in 16 Ni-rich samples selected among the 100 soils showed a strong effect
      of the mineralogy of the bearing phases on Ni availability (IEK). Plants with
      different Ni accumulation strategies all took up Ni from the same labile pool of
      Ni in four contrasting soils, and the amount taken up by hyperaccumulator plants
      could be anticipated with the IEK parameters, thus confirming the usefulness of
      isotopic dilution methods for risk assessment.

PMID- 16566148
TI  - Short-term natural attenuation of copper in soils: effects of time, temperature,
      and soil characteristics.
AB  - Natural attenuation of metals added to soils refers to the processes by which the
      mobility and bioavailability/toxicity of the added metals decline with time. In
      this paper, we used isotopic dilution techniques to investigate the short-term
      (30 d) natural attenuation of Cu added to 19 European soils at two effective
      concentrations shown to inhibit plant (tomato) growth by 10 and 90%. The results
      showed that the lability of Cu added to soils rapidly decreased after addition,
      especially in the soils with pH > 6.0, followed by a slow decrease in Cu
      lability. The lability of Cu added to soils also decreased with increasing
      incubation temperature. The activation energies and the apparent diffusion rate
      coefficients for the attenuation processes were 33 to 36 kJ/mol and 0.66 to 20.9
      x 10(-10)/s at 20 degrees C, respectively, and were consistent with Cu diffusion
      in meso- and micropores. The attenuation of Cu lability was modeled on the basis
      of three processes: precipitation/nucleation of Cu on soil surfaces, Cu occlusion
      within organic matter, and diffusion of Cu into micropores. The soil and
      environmental factors governing attenuation rates were soil pH, organic matter
      content, incubation time, and temperature. Soil pH is the key factor for natural
      attenuation of Cu added to soils. The model can be used to scale ecotoxicological
      data generated from different soils and under different incubation times and
      temperatures.

PMID- 16566149
TI  - Kinetics of metal fixation in soils: measurement and modeling by isotopic
      dilution.
AB  - The bioavailability of metal contaminants in soils varies widely, depending on
      soil characteristics and the source of the contaminant. As a consequence, site
      specific risk assessment requires accurate prediction of the bioavailable (or
      labile) fraction of soil metal. Moreover, metals in soil are subject to time
      dependent processes, which affect their bioavailability and thereby complicate
      the prediction of future risk. The aim of the present study was to describe the
      development of simple, readily applicable models for the time-dependent changes
      in lability of Cd and Zn in soils. We present data showing the time-dependent
      behavior of radiolabile and soil solution concentrations of Cd and Zn during an
      incubation study over a period of 813 d in 23 diverse soils. The data are used to
      parameterize candidate models of metal fixation in soils designed to be readily
      applicable and therefore relevant to risk assessment. We conclude that the final
      extent of metal fixation increases with pH and generally is greater for Zn than
      for Cd; however, the rate of fixation is independent of pH and equivalent to a
      half-time to equilibrium of 29 and 89 d for Cd and Zn, respectively. It is
      possible that longer-term processes occur, especially for Zn, but these could not
      be detected in the present study.

PMID- 16566150
TI  - Kinetics of zinc and cadmium release in freshly contaminated soils.
AB  - The kinetics of metal release from the solid phase to solution was measured on
      two sets of 14 freshly contaminated soils with diverse properties. From
      measurements of metal concentrations in extracted soil pore water, the amount
      accumulated from the soil by diffusive gradients in thin-film (DGT) devices, and
      the distribution coefficient for labile metal, Kdl, estimated by isotopic
      exchange, we calculated the response time, Tc, of the soil-solution system to the
      removal of metal by DGT and the rate constant for release from the solid phase,
      k(-1). Resupply was so fast for Zn that Tc (and k(-1)) could be measured only in
      three of the soils, with either a silty or a sandy loam texture and low to
      intermediate pH (4.84-5.66). In only six clay soils was resupply of Cd too fast
      to measure. The generally slower release rates of Cd compared to Zn may reflect
      the 100-fold lower concentration of Cd, which allowed a greater proportion of it
      to occupy stronger binding sites with slower release rates. The rate constants
      derived indicate that supply from the solid phase to solution will not limit
      uptake of Cd or Zn by plants in clay soils, but it could be a factor in sandy or
      silty soils with a low pH. These findings suggest that risk assessment of clay
      soils could be undertaken using measurements of metals in soil solution. However,
      devices such as DGT, which respond to the kinetics of supply, are necessary to
      assess available metal in low pH, sandy, and silty soils.

PMID- 16566151
TI  - Effect of soil properties on copper release in soil solutions at low moisture
      content.
AB  - Copper partitioning at moisture content of 1.2-fold the field moisture capacity
      (corresponding to a soil water potential of 7.84 J/kg; pF = 1.9) was studied in
      11 soils with pH 3.4 to 6.8 and an organic matter content of 4.1 to 233 g C/kg.
      Soil solutions were separated with the centrifuge method and analyzed to
      determine pH, Cu2+ activity, dissolved organic carbon, and Cu, Ca, Mg, and Na
      concentrations. Soil organic matter content, total Cu content, and soil pH were
      the main variables explaining variation in Cu activity in soil solutions. Based
      on total Cu, soil organic matter content, and soil solution pH, the Windermere
      Humic Aqueous Model (WHAM) VI assemblage model provided estimates of Cu2+
      activity, {Cu2}, with a root mean square error of the predicted pCu (i.e., 
      log{Cu2+}) of 0.77.

PMID- 16566152
TI  - Model studies of corrosion-induced copper runoff fate in soil.
AB  - Laboratory experiments have been performed with 3-cm soil columns simulating the
      fate of corrosion-induced copper runoff in contact with soil. The investigation
      simulates approximately 30 years (assuming an infiltration surplus of 25 cm/year)
      of continuous percolation of copper containing runoff water of a concentration
      realistic at the immediate release situation (4.8 mg/L) into four soils
      representative of urban conditions. Two of the three investigated topsoils
      reached their breakthrough of copper within the simulated time, while the third
      topsoil did not show a breakthrough. The subsoil reached a breakthrough after
      approximately 10 years of simulated exposure. To simulate more realistic outdoor
      scenarios, the laboratory-obtained breakthrough curves were modeled with Hydrus
      1D using a Langmuir-Freundlich model to describe copper sorption, the parameters
      of which were estimated from soil properties (pH, organic carbon content). The
      model predicts longer breakthrough times with increasing pH and organic content
      of the soil and with decreasing concentrations of copper and dissolved organic
      carbon in the runoff water. The time span for copper in runoff water (at
      concentrations of 0.01-10 mg/L) to reach a soil depth of 50 cm varied between 170
      and more than 8,000 years for the predicted field scenarios.

PMID- 16566153
TI  - Rhizotoxicity of cadmium and copper in soil extracts.
AB  - Dissolved organic matter (DOM) influences metal speciation in soil solutions and,
      hence, metal toxicity. Root-elongation experiments were conducted to examine the
      effect of soil solution components, such as Ca, H, and DOM, on metal
      rhizotoxicity. A biotic ligand model (BLM) was tested for its ability to predict
      the rhizotoxicity of Cd and Cu in soil extracts. It was hypothesized that the
      concentration of Cd and Cu bound to functional groups at the root surface
      estimated using a BLM would be a better predictor of rhizotoxicity than the free
      metal ion activity in solution. Both metals became less toxic at higher DOM, Ca,
      and H concentrations. Solution speciation and the effect on root growth explained
      most of the variability observed in the DOM experiments, but not in the cation
      experiments. It was concluded that Ca and H inhibited the rhizotoxicity of both
      metals tested. Rhizotoxicity data correlated better with estimates of metal-root
      complexes that have been estimated with a BLM than with free-metal ion activity
      or with total metal concentrations. The BLM seems to be a promising approach for
      predicting metal availability in soils and for assessing the associated risk.

PMID- 16566154
TI  - Effects of humic acid and competing cations on metal uptake by Lolium perenne.
AB  - Within the biotic ligand model, which describes relationships between chemical
      speciation and metal binding at an organism's surface, multicomponent (long-term)
      metal uptake by plants has seldom been studied. In the present work, we exposed
      perennial ryegrass to nutrient solutions with two levels of Cd, Cu, Ni, Pb, and
      Zn (1 and 0.1 microM) and with or without 30 mg/L of humic acid. Iron and Mn
      concentrations were constant over all treatments. The hypothesis tested was that
      humic acid lowers the free and labile metal concentration and, therefore, reduces
      the metal uptake and, finally, the metal content of the plant. The free metal ion
      concentrations in the nutrient solutions were measured by the Donnan membrane
      technique and labile metal concentrations by diffusive gradients in thin-films.
      The metal content of the shoots depends on the metal content of the roots. The
      metal content of the roots is a function of the adsorption of metals on the root
      surface. In a multicomponent system at metal concentrations of 1 microM, humic
      acid decreased Cu, Pb, and Fe adsorption at the root surface, but it increased
      Cd, Zn, and Mn adsorption at the root surface. Complexation of cations such as
      Cu, Pb, and Fe with high affinity for (dissolved) organic matter may lead to
      increased uptake of cations with low affinity for organic matter (Ni, Zn, and Cd)
      because of competition between cations at the root surface. The results suggest
      that competition between metal ions can play a major role in multicomponent metal
      uptake, which has to be taken into account during risk assessments of metal
      polluted soils.

PMID- 16566155
TI  - Agricultural soils spiked with copper mine wastes and copper concentrate:
      implications for copper bioavailability and bioaccumulation.
AB  - A better understanding of exposure to and effects of copper-rich pollutants in
      soils is required for accurate environmental risk assessment of copper. A
      greenhouse experiment was conducted to study copper bioavailability and
      bioaccumulation in agricultural soils spiked with different types of copper-rich
      mine solid wastes (copper ore, tailing sand, smelter dust, and smelter slag) and
      copper concentrate. A copper salt (copper sulfate, CuSO4) that frequently is used
      to assess soil copper bioavailability and phytotoxicity also was included for
      comparison. Results showed that smelter dust, tailing sand, and CuSO4 are more
      likely to be bioavailable and, thus, toxic to plants compared with smelter slag,
      concentrate, and ore at equivalent total copper concentrations. Differences may
      be explained by intrinsic differences in copper solubilization from the source
      materials, but also by their capability to decrease soil pH (confounding effect).
      The copper toxicity and bioaccumulation in plants also varied according to soil
      physicochemical characteristics (e.g., pH and total organic carbon) and the
      available levels of plant nutrients, such as nitrogen, phosphorus, and potassium.
      Chemistry/mineralogy of mine materials, soil/pore-water chemistry, and plant
      physiological status thus should be integrated for building adequate models to
      predict phytotoxicity and environmental risk of copper.

PMID- 16566156
TI  - Evaluating the contribution of soil properties to modifying lead
      phytoavailability and phytotoxicity.
AB  - Soil properties affect Pb bioavailability to human and ecological receptors and
      should be considered during ecological risk assessment of contaminated soil. We
      used path analysis (PA) to determine the relative contribution of soil properties
      (pH, organic C [OC], amorphous Fe and Al oxides [FEAL], and cation-exchange
      capacity [CEC]) in modifying Pb bioavailability. The response of biological
      endpoints (bioaccumulation and dry matter growth [DMG]) of lettuce (Lactuca
      sativa) grown on 21 Pb-spiked (2,000 mg/kg) soils were determined. Lettuce tissue
      Pb ranged from 3.22 to 233 mg/kg, and relative DMG ranged from 2.5 to 88.5% of
      their respective controls. Simple correlation showed strong relationships between
      CEC and OC (p < 0.01) and weaker relationships between pH and FEAL (p < 0.05) and
      Pb bioaccumulation. Results of PA suggest that soil pH increased the negative
      surface charge of organic matter and clay, thereby increasing CEC and decreasing
      Pb bioaccumulation. Also, the direct effect of OC on tissue Pb can be attributed
      to formation of surface Pb complexes by organic matter functional group ligands.
      Increased OC and/or CEC reduced Pb solubility and bioavailability in the 21 soils
      in the present study. The relative importance of soil properties likely will vary
      between studies employing different soils. Soil properties should be considered
      during the ecological risk assessment of metal in contaminated soils. Path
      analysis is useful for ecological studies involving soils with a wide range of
      physicochemical properties and can assist in site risk assessment of metals and
      remediation decisions on contaminated sites.

PMID- 16566157
TI  - Soil factors controlling the expression of copper toxicity to plants in a wide
      range of European soils.
AB  - The impact of soil properties on metal bioavailability to plants is well
      recognized. However, the effect of soil bioavailability parameters on toxicity
      threshold values for Cu in plants needs quantification. Eighteen European soils
      varying widely in soil properties were amended with CuCl2 to obtain a range of
      seven concentrations including an unamended control. Two plant toxicity assays,
      barley root elongation (4 d) and tomato shoot growth (21 d after emergence), were
      performed on each soil under controlled environment conditions. The effective
      concentration of added Cu causing 50% inhibition (EC50) ranged from 36 to 536
      mg/kg soil and from 22 to 851 mg/kg soil for barley root elongation and tomato
      shoot growth, respectively, representing variation in EC50 among soils of 15- and
      39-fold. Single regressions carried out between Cu toxicity threshold values and
      various soil properties showed that exchangeable calcium and soil cation exchange
      capacity (CEC; measured at soil pH) were the best single predictors for toxicity
      values from both plant tests. The inclusion of other soil properties, such as
      iron oxide concentration, soil pH, clay, or organic carbon content, further
      improved predictions. For risk assessment, we suggest that Cu toxicity threshold
      values (EC50) be normalized on the key soil property of CEC. If available, soil
      exchangeable calcium and iron oxide concentration would improve the
      normalization.

PMID- 16566158
TI  - Comparison of soil solution speciation and diffusive gradients in thin-films
      measurement as an indicator of copper bioavailability to plants.
AB  - The toxicity effect concentrations (10% effective concentration [EC10] and 50%
      effective concentration [EC50]) of total added Cu derived from barley root
      elongation and tomato growth assays varied widely among 18 European soils. We
      investigated whether this variation could be explained by the solubility or
      speciation of Cu in soil solutions or the diffusive gradients in thin-films (DGT)
      measurement. Solubility and Cu speciation varied greatly among the soils tested.
      However, the EC10 and EC50 of soil solution Cu or free Cu2+ activity varied even
      more widely than those based on the total added Cu, indicating that solubility or
      soil solution speciation alone could not explain intersoil variation in Cu
      toxicity. Estimated EC10 and EC50 of free Cu2+ activity correlated closely and
      negatively with soil pH, indicating a protective effect of H+, which is
      consistent with the biotic ligand model concept. The DGT measurement was found to
      narrow the intersoil variation in EC50 considerably and to be a better predictor
      of plant Cu concentrations than either soil solution Cu or free Cu2+ activity. We
      conclude that plant bioavailability of Cu in soil depends on Cu speciation,
      interactions with protective ions (particularly H+), and the resupply from the
      solid phase, and we conclude that the DGT measurement provides a useful indicator
      of Cu bioavailability in soil.

PMID- 16566159
TI  - Effect of a copper gradient on plant community structure.
AB  - Vegetation data including plant cover, biomass, species richness, and vegetation
      height was sampled on a copper-contaminated field with total copper contents
      varying from 50 to almost 3,000 mg/kg soil. The field was covered by early
      succession grassland dominated by Agrostis stolonifera. Plant cover, biomass,
      species richness, and vegetation height generally decreased with increasing
      copper content, although the highest biomass was reached at intermediate copper
      concentrations. Multivariate statistical analyses showed that plant community
      composition was significantly correlated with soil copper concentration and that
      community composition at soil copper concentrations above 200 mg/kg differed
      significantly from community composition at lower copper levels. Comparison of
      single-species (Black Bindweed, Fallopia convolvulus) performance at the field
      site and in laboratory tests involving field soil and spiked soil indicates that
      the laboratory tests conventionally applied for risk assessment purposes do not
      overestimate copper effects. Interaction between copper and other stressors
      operating only in the field probably balance the higher bioavailability in spiked
      soil.

PMID- 16566160
TI  - Toxicity benchmarks for antimony, barium, and beryllium determined using
      reproduction endpoints for Folsomia candida, Eisenia fetida, and Enchytraeus
      crypticus.
AB  - The U.S. Environmental Protection Agency is developing ecological soil screening
      levels (Eco-SSLs) for the ecological risk assessment of contaminants at Superfund
      sites. The Eco-SSLs for several soil contaminants have been developed from
      toxicity benchmarks for soil invertebrates in the existing literature.
      Insufficient information to generate Eco-SSLs for Sb, Ba, and Be necessitated
      toxicity testing to fill the data gaps. We used standardized toxicity tests with
      the earthworm Eiseniafetida, enchytraeid Enchytraeus crypticus, and collembolan
      Folsomia candida in the present study. These tests were selected on the basis of
      their ability to measure chemical toxicity to ecologically relevant test species
      during chronic assays and their inclusion of at least one reproduction component
      among the measurement endpoints. Tests were conducted in Sassafras Sandy Loam
      soil, which supports relatively high bioavailability of metals. Weathering and
      aging procedures for metals in amended soil were incorporated into these studies
      to better reflect exposure conditions in the field. The relative toxicity of
      metals to the soil invertebrates tested was Be > Sb > Ba based on the median
      effective concentration values for reproduction. These studies produced
      toxicological data that can contribute to the development of Eco-SSLs for Sb, Ba,
      and Be for soil invertebrates.

PMID- 16566161
TI  - Tungsten effects on survival, growth, and reproduction in the earthworm, Eisenia
      fetida.
AB  - To provide basic toxicity data for formulating risk characterization benchmarks,
      the effects of tungsten on survival, growth, and reproduction were investigated
      in the earthworm Eisenia fetida. Parallel studies with lead as a reference
      toxicant also were conducted. Although sodium tungstate (Na2WO4) was less acutely
      toxic than lead nitrate (Pb(NO3)2) in 14-d spiked field soil acute toxicity
      assays (lethal concentrations for 50% of organisms: W, 6,250 mg/kg; Pb, 2,490
      mg/kg), tungstate completely inhibited reproduction in 28- and 56-d assays at all
      tested tungsten concentrations (> or = 704 mg/kg). By comparison, cocoon
      production was not significantly reduced for lead concentrations until
      concentrations reached 766 mg/kg, and cocoon production was still observed at the
      highest concentration tested (1,650 mg/kg). These data indicate that tungsten is
      a reproductive toxicant for earthworms and that, by comparison, its sublethal
      toxicity is greater than that of lead. Toxicity data for other soil invertebrate
      species are required to fully establish benchmark levels/ecological soil
      screening levels for tungsten.

PMID- 16566162
TI  - Effect of soil properties on lead bioavailability and toxicity to earthworms.
AB  - Soil properties are important factors modifying metal bioavailability to
      ecological receptors. Twenty-one soils with a wide range of soil properties (USA;
      http://soils.usda.gov/technical/classification/taxonomy/) were amended with a
      single concentration of Pb (2,000 mg/kg) to determine the effects of soil
      properties on Pb bioavailability and toxicity to earthworms. Earthworm mortality
      ranged from 0 to 100% acute mortality following exposure to the same total
      concentration of Pb (2,000 mg/kg) in amended field soils. Internal Pb
      concentrations in earthworms ranged from 28.7 to 782 mg/kg, with a mean of 271
      mg/kg. Path analysis was used to partition correlations in an attempt to discern
      the relative contribution of each soil property. Results of path analysis
      indicated that pH was the most important soil property affecting earthworm
      mortality (p < 0.01) and internal Pb (p < 0.05). Soil pH was related inversely to
      mortality and internal Pb, soil solution Pb, and Pb bioavailability. The most
      important soil property modifying reproduction was amorphous iron and aluminum
      oxides (FEAL). Because FEAL is rich in pH-dependent cation-exchange sites,
      several soil properties, including pH, FEAL, and cation-exchange capacity, have a
      causal effect on Pb adsorption and soluble Pb. Path analysis is useful for
      assessing contaminated soils with a wide range of soil properties and can assist
      in ecological risk assessment and remediation decisions for contaminated sites.
      Soil properties are important factors modifying metal bioavailability and
      toxicity and should be considered during the ecological risk assessment of metals
      in contaminated soils.

PMID- 16566163
TI  - Improvement of the applicability of ecotoxicological tests with earthworms,
      springtails, and plants for the assessment of metals in natural soils.
AB  - The environmental risk assessment of metals in the soil compartment is based
      mainly on tests performed in Organization for Economic Cooperation and
      Development (OECD) artificial soil, but ecologically, the use of natural soils
      would be more relevant. In this contribution, the reproduction and growth of
      three standard species (an earthworm, a collembolan, and a dicotyledonous plant,
      respectively) was evaluated in nine natural soils (covering a wide range of pH
      values, organic matter content, texture, and so on) and in OECD artificial soil.
      Afterward, the effects of the model chemical zinc nitrate were assessed in all
      soils that were identified as being suitable for these species. The test results
      indicate that the toxicity of zinc nitrate can be higher by a factor of
      approximately four compared to artificial soil for invertebrates (earthworms and
      collembolans), whereas plants are only slightly more sensitive in some natural
      soils than in artificial soil. When comparing the different endpoints, it could
      be confirmed that the median effective concentration (EC50) is the most robust
      compared to the highly uncertain 10% effective concentration. Decreasing toxicity
      of zinc nitrate to collembolans was significantly correlated with an increase in
      soil pH but not with cation exchange capacity (CEC) or organic carbon (OC)
      content. No significant correlation was found between the toxicity of zinc
      nitrate to earthworms or plants and soil pH, CEC, or OC content. Possible
      consequences of the results are discussed, such as the testing of natural soils
      in addition to the OECD artificial soil or the inclusion of an additional safety
      factor to use the EC50 in current risk assessment schemes focusing on no-observed
      effect concentrations.

PMID- 16566164
TI  - Effect of pH on metal speciation and resulting metal uptake and toxicity for
      earthworms.
AB  - In the present study, relationships between changes in the solubility and
      speciation of metals in contaminated soils under different pH regimes and their
      toxicity to earthworms were investigated. Earthworms (Lumbricus rubellus) were
      exposed in a laboratory bioassay to metalliferous soils under three pH regimes:
      Unamended pH, pH lowered by one unit (pH -1), and pH increased by one unit (pH
      +1). In each soil, total (hot nitric acid-extractable) and 0.01 M CaCl2
      extractable metal concentrations were measured and soil pore-water chemistry
      analyzed to allow metal speciation to be modeled using the Windermere Humic
      Aqueous Model. Earthworm metal accumulation was determined and toxicity assessed
      by measuring survival and reproduction and at the molecular level by recording
      expression of the gene encoding metallothionein-2 (MT-2) using quantitative
      reverse transcriptase-polymerase chain reaction. Both metal solubility and
      speciation were found to be highly pH dependent. Metal accumulation in earthworms
      was influenced by soil concentration and, in some cases (e.g., Cd), by pH.
      Reproduction was affected (reduced up to 90%) by soil metal level, pH, and their
      interaction. Relationships between analyzed and calculated Zn concentrations and
      toxicity and between analyzed and calculated Cd concentrations and tissue
      accumulation and MT-2 expression were compared by fitting dose-response models
      and assessing the fit of the data. This analysis indicated that values based on a
      pH-adjusted free ion concentration best explained toxicity (r2 = 0.82) and
      accumulation (r2 = 0.54). Expression of MT-2 was, however, poorly correlated (p >
      0.05) with all analyzed and modeled soil metal concentrations.

PMID- 16566165
TI  - How terrestrial snails can be used in risk assessment of soils.
AB  - Among soil invertebrates, terrestrial snails are herbivorous and detritivorous
      organisms exposed to polluted soils by both digestive and cutaneous routes. Using
      laboratory-reared snails (Helix aspersa aspersa), we describe how the effects of
      contaminants on survival and growth of snails can be evaluated in laboratory
      bioassays. A national ring test was performed to assess the effect of Cd added to
      the soil or to the food. The ecotoxicity of sewage sludge also was evaluated. The
      present results demonstrate that toxicity depends on both the pollutants and the
      exposure route. Cadmium was sixfold more toxic for snails exposed via food
      contamination (median effective concentration [EC50], 68-139 microg/g) than via
      soil contamination (EC50, 534-877 microg/g), whereas the opposite occurred with
      the sewage sludge (EC50, 55% of sludge in the food and 10% of waste in the soil).
      A logistic relationship linked growth inhibition and internal Cd concentrations,
      which can reach 2,000 microg/g in the viscera of snails exposed to 626 microg/g
      in the food. No clear trend was found between Cu, Zn, Pb, Cr, and Ni
      concentrations in the sludge and in snail tissues. These data enabled the
      development of an international standard, which should enhance the use of
      terrestrial gastropods for both fundamental research and routine risk assessment
      in the terrestrial environment.

PMID- 16566166
TI  - Biological significance of metals partitioned to subcellular fractions within
      earthworms (Aporrectodea caliginosa).
AB  - Metal ions in excess of metabolic requirements are potentially toxic and must be
      removed from the vicinity of important biological molecules to protect organisms
      from adverse effects. Correspondingly, metals are sequestrated in various forms,
      defining the accumulation pattern and the magnitude of steady-state levels
      reached. To investigate the subcellular fractions over which Ca, Mg, Fe, Cu, Zn,
      Cd, Pb, Ni, and As are distributed, earthworms (Aporrectodea caliginosa)
      collected from the field were analyzed by isolating metal-rich granules and
      tissue fragments from intracellular microsomal and cytosolic fractions (i.e.,
      heat-stable proteins and heat-denatured proteins). The fractions showed metal
      specific binding capacity. Cadmium was mainly retrieved from the protein
      fractions. Copper was equally distributed over the protein fraction and the
      fraction comprising tissue fragments, cell membranes, and intact cells. Zinc, Ca,
      Mg, and As were mainly found in this fraction as well. Lead, Fe, and Ni were
      mainly isolated from the granular fraction. To study accumulation kinetics in the
      different fractions, three experiments were conducted in which earthworms were
      exposed to metal-spiked soil and a soil contaminated by anthropogenic inputs and,
      indigenous earthworms were exposed to field soils. Although kinetics showed
      variation, linear uptake and steady-state types of accumulation patterns could be
      understood according to subcellular compartmentalization. For risk assessment
      purposes, subcellular distribution of metals might allow for a more precise
      estimate of effects than total body burden. Identification of subcellular
      partitioning appears useful in determining the biological significance of steady
      state levels reached in animals.

PMID- 16566167
TI  - Transfer of Cd, Cu, Ni, Pb, and Zn in a soil-plant-invertebrate food chain: a
      microcosm study.
AB  - The transfer of Cd, Cu, Ni, Pb, and Zn was evaluated in a soil-plant (lettuce,
      Lactuca sativa)-invertebrate (snail, Helix aspersa) food chain during a microcosm
      experiment. Two agricultural soils, polluted and unpolluted, were studied.
      Lettuce was cultivated for eight weeks before introduction of snails into the
      microcosms (M-snails). In a parallel experiment, snails were exposed to lettuce
      only (i.e., without soil) in simpler exposure devices called containers (C
      snails). Snail exposure duration was eight weeks for both M- and C-snails. No
      effects on snail survival were found. Both M- and C-snails exposed to polluted
      soil showed a growth reduction, but only after two weeks of exposure. Time
      dependent accumulation in M-snails exposed to the polluted environment showed a
      regular increase of Cd and Zn concentrations over time and a rapid increase of Pb
      concentrations within the first two weeks, which then remained stable. Copper and
      Ni concentrations did not increase during any of the experiments. Concentrations
      in M- and C-snails were compared to estimate the relative contribution of soil
      and plant to the total bioaccumulation. The results suggest that the soil
      contribution may be higher than 80% for Pb, from 30 to 60% for Zn, and from 2 to
      40% for Cd.

PMID- 16566168
TI  - Effects of metal-contaminated forest soils from the Canadian shield to
      terrestrial organisms.
AB  - The effects of elevated metal concentrations in forest soils on terrestrial
      organisms were investigated by determining the toxicity of six site soils from
      northern Ontario and Quebec, Canada, using a battery of terrestrial toxicity
      tests. Soils were collected from three sites on each of two transects established
      downwind of nickel (Sudbury, ON, Canada) and copper (Rouyn-Noranda, PQ, Canada)
      smelting operations. Site soils were diluted to determine if toxicity estimates
      for the most-contaminated site soils could be quantified as a percent of site
      soil. Rouyn-Noranda soils were toxic following acute exposure (14 d) to plants,
      but not to invertebrates (7 d for collembola and 14 d for earthworms). However,
      Rouyn-Noranda soils were toxic to all species following chronic exposure (21, 35,
      and 63 d for plants, collembola, and earthworms, respectively). The toxicity of
      the Rouyn-Noranda site soils did not correspond to the gradient of metal
      concentrations in soil. Metal-contaminated Sudbury soils were toxic to plants but
      not to invertebrates, following acute exposure. Chronic exposure to Sudbury soils
      caused adverse effects to plant growth and invertebrate survival and
      reproduction. The toxicity of Sudbury soils corresponded to the metal
      concentration gradient, with one exception: The reference soil collected in
      October was toxic to collembola following acute and chronic exposure. This study
      evaluated the applicability of the new Environment Canada terrestrial toxicity
      test methods, developed using agricultural soils, to forest soils and also
      provided useful data to assess the ecological risk associated with mixtures of
      metals in soil.

PMID- 16566169
TI  - Soil properties affecting the toxicity of CuC12 and NiC12 for soil microbial
      processes in freshly spiked soils.
AB  - It generally is unknown to what extent the toxicity of Cu and Ni for soil
      microbial processes varies among different soils. A comparative study was made
      using three different microbial assays (nitrification potential, glucose-induced
      respiration, and C-mineralization of a plant residue) in 19 (for Cu) or 16 (for
      Ni) soils with contrasting soil properties. Each soil was spiked with CuCl2 or
      NiCl2 at seven different concentrations, and the bioassays were started after a 7
      d equilibration period. The Cu and Ni toxicity thresholds varied 19- to 90-fold
      among soils. The differences in both Cu and Ni toxicity among soils were neither
      explained by soil solution metal concentrations nor by free ion activities
      calculated from soil solution composition. Copper toxicity thresholds (total
      concentrations) increased with increasing organic matter content or cation
      exchange capacity (CEC) and, surprisingly, decreased with increasing pH depending
      on the assay. Nickel toxicity thresholds consistently increased with increasing
      CEC, background Ni, and clay content for all three assays. Thresholds expressed
      as soil solution free ion activities all significantly decreased with increasing
      soil solution pH (r2 = 0.57-0.93), consistent with a decreased H+:M2+ competition
      at the biological membrane. That competition largely counteracts the H+:M2+
      competition for sorption, effectively explaining the insignificant or weak effect
      of pH on total Ni or Cu toxicity thresholds. It is concluded that free metal-ion
      activity alone does not explain variation in metal toxicity among soils.

PMID- 16566170
TI  - Discrepancy of the microbial response to elevated copper between freshly spiked
      and long-term contaminated soils.
AB  - A systematic comparison of Cu toxicity thresholds was made between freshly spiked
      soils and soils in which elevated Cu concentrations have been present for various
      times. Three uncontaminated soils were spiked and experimentally leached or
      incubated outdoors for up to 18 months. Additionally, five field-contaminated
      soils with a 6- to 80-year-old Cu contamination were sampled, and corresponding
      uncontaminated soils were spiked to identical total concentrations. All soil
      samples were subjected to three microbial assays (nitrification potential,
      glucose-induced respiration, and maize residue C-mineralization). Experimental
      leaching or soil incubation after spiking reduced Cu toxicity (1.3- or 2.3-fold
      increase of dose, respectively, to inhibit process by 50% [ED50]). No significant
      effects of soil type, aging time (6, 12, or 18 months), or bioassay on the factor
      change of ED50 were found. Significant reductions of microbial activity in field
      contaminated soils were only identified in 2 of the 15 series (three assays in
      five soils), whereas freshly spiking the corresponding control soils
      significantly affected these processes in 12 series. Soil solution Cu
      concentrations significantly decreased on leaching at corresponding total soil
      Cu, and smaller decreases were found during additional aging. Soil solution Cu
      concentrations largely explain changes in Cu toxicity on leaching and aging,
      although additional variation may be related to changes in the sensitivity of
      microbial populations. It is concluded that total Cu toxicity thresholds are
      lower in freshly spiked soils compared to soils in which Cu salts have
      equilibrated and leaching has removed excess soluble salts. The large variability
      of soil microbial processes creates a large uncertainty about the magnitude of
      the factor by which aging mitigates Cu toxicity.

PMID- 16566171
TI  - Copper inhibition of soil organic matter decomposition in a seventy-year field
      exposure.
AB  - On a site contaminated decades ago with Cu from a wood treatment facility, we can
      observe that the decomposition of soil organic matter has been slowed. This
      represents an exceptional data set, and it allows us to address many challenges
      faced by regulators and risk assessors who are trying to derive appropriate soil
      quality criteria. These data are representative of a field study with a very well
      equilibrated contamination and allow the derivation of chronic toxicity threshold
      values for the inhibition of microbial respiration. Soil respiration is the main
      determinant of the carbon balance, and it is assessed using the accumulation of
      soil organic matter (SOM) in this case. Using data derived from a 70-year-old
      field study also has the advantage of not being subject to risk assessment
      uncertainty factors arising from the potential aging effects of spiked soil or to
      the uncertainty caused by laboratory-to-field differences, both of which are very
      difficult to address. The resulting toxicity thresholds for an inhibition of SOM
      degradation are 154, 193, and 285 mg Cu/kg dry soil for inhibition levels of 10,
      20, and 50%, respectively. Setting those thresholds correctly is critical for a
      proper risk assessment relative to sustainable development and agriculture.

PMID- 16566172
TI  - Ambient copper concentrations in agricultural and natural European soils: an
      overview.
AB  - Copper concentrations in soil are affected by a large number of processes related
      to the natural spatial variability (geochemistry), the amount released, the
      spatial and temporal distributions of these releases, and the large number of
      transportation, complexation, and dissolution processes. The present study
      reports the generated country-specific and land use-specific environmental
      concentration distributions of ambient copper exposure levels in European soils
      that were used for the derivation of "reasonable worst-case" predicted
      environmental copper concentrations (RWC-ambient copper PEC) for three types of
      soil uses: Agricultural soils, forest soils, and undefined grassland soils. Only
      recent and high-quality monitoring data (Q1) that comply with a number of
      criteria (i.e., sampling strategy, land use, digestion method, and absence of
      point sources) were selected for this purpose. Data treatment procedures used in
      the present study were based on the methods and concepts laid down in the
      European Union Technical Guidance Document on Risk Assessment and in the
      "combined monitoring-based and modeling-based priority setting" procedure. The
      derived median RWC-ambient copper PEC for European agricultural soils is 31.1
      mg/kg dry weight, with the lowest and highest RWC-ambient copper PEC found in
      Belgium (16.1 mg/kg dry wt) and northern Italy (57.5 mg/kg dry wt), respectively.
      The high value for Italian soils probably is related to the (recent) volcanic
      origin of these soils. Similarly, RWC-ambient copper PECs were derived for forest
      soils and undefined grassland soils (24.4 and 35.3 mg/kg, respectively). Observed
      differences between the diifferent soil uses could be related to various
      parameters and processes that determine the copper levels in soil (e.g., soil
      type associated with specitic soil uses, addition of fertilizers and pesticides,
      and presence of cattle).

PMID- 16566173
TI  - Plant toxicity testing to derive ecological soil screening levels for cobalt and
      nickel.
AB  - Phytotoxicity tests were performed to set ecological soil screening levels for
      cobalt (Co) and nickel (Ni) following the American Society for Testing and
      Materials international E1963-98 Standard Guide for Conducting Terrestrial Plant
      Toxicity Tests. Two soils (a modified artificial soil mixed with 5% organic
      matter, pH 5.01, and a native riverine sandy soil with 0.1% organic matter, pH
      6.3) were treated with cobalt(II) chloride or nickel chloride and allowed to age
      for four weeks before initiating tests. Alfalfa, barley, radish, perennial rye,
      and brassica were used to determine the appropriate range of concentrations and
      to select the most sensitive plant species for definitive tests. The tests were
      designed to have one to three test concentrations below the 20% effects
      concentration (EC20), and five to six test concentrations above the EC20.
      Definitive tests for each chemical used two soil matrices, three plant species,
      and replicates at 10 nominal concentrations, including negative control. Soil
      chemical concentrations were determined before planting and on completion of the
      phytotoxicity tests. Threshold responses interpreted as the EC20 for each species
      endpoint were calculated from regression analyses. The geometric mean of the EC20
      values (excluding emergence, mortality, and nodule numbers) for each species
      resulted in values of 30.6 mg/kg for Co and 27.9 mg/kg for Ni.

PMID- 16566174
TI  - The biotic ligand model for plants and metals: technical challenges for field
      application.
AB  - To improve predictions of phytoavailable metal, the mechanistic bases of
      bioaccumulation and toxicity of metals to plants can be integrated into a biotic
      ligand model (BLM). There are a number of significant challenges to the
      application of the BLM to plants in soils, including reliable measurements of
      free ion concentrations for the metals of interest in rhizospheric soil solution,
      as well as other free ions, and concentrations of ligands to which the ions could
      bind; identification of the simplest model that can adequately predict root
      accumulation, and the potential for more complex models to add accuracy to the
      predictions; incorporating the dissociation of labile metal complexes (i.e.,
      nonequilibrium processes) into a BLM, which is an equilibrium model; application
      of factors in a BLM that adequately describe translocation, in order to estimate
      metal concentration and speciation in plant shoots. The review concluded that the
      ability to estimate trace metal speciation in samples of soil solution are not
      likely to be better than within one order of magnitude of actual, thus this would
      be an additional source of uncertainty to the predictions of toxicity. Further,
      regulatory use of the BLM would require mechanistic bases; and, until root
      ligands associated with toxicity are well characterized, incorporating the
      ameliorative effects of competitive cations cannot be mechanistically based. As
      well, a functional BLM for soils with lower metal free ion activities will have
      to include kinetic data for metal-ligand complexes, as their
      association/disassociation may constitute a greater metal supply to roots than
      what would be predicted by the free ion concentration in soil solution. To apply
      the BLM to trophic transfer where metal concentration in plant shoots is the main
      focus, a probabilistic approach using experimentally determined root-shoot
      partitioning of metals might permit estimates of shoot accumulation from root
      data, to within one or two orders of magnitude.

PMID- 16566175
TI  - Developing a critical load approach for national risk assessments of atmospheric
      metal deposition.
AB  - The critical load approach has been proposed for evaluation of the need to reduce
      atmospheric emissions of metals that lead to transboundary transport and
      deposition across Europe. The present study demonstrates and evaluates the
      application of a critical load approach for national-scale risk assessment of
      metal deposition in the United Kingdom. Critical load maps, calculated using
      critical limits based on pH-dependent free metal ion activities, are presented.
      Current concentrations of lead and cadmium in soils are compared with two sets of
      critical limit values: First, limits based on the reactive soil concentration,
      and second, a pH-dependent free ion critical limit function, which takes into
      account variable soil characteristics across the country. The use of these two
      models leads to different conclusions about which areas of the United Kingdom are
      at greatest risk, partly because of differences in the range of values of pH and
      organic matter in soils used in ecotoxicological experiments and in the national
      database. Critical loads were calculated based on free ion critical limits; the
      critical loads were lowest in the south and east of the country and were
      associated with higher soil pH, lower runoff, and lower soil organic matter.

PMID- 16566176
TI  - Long-term corrosion-induced copper runoff from natural and artificial patina and
      its environmental impact.
AB  - The overall objective of this paper is to present an extensive set of data for
      corrosion-induced copper dispersion and its environmental interaction with solid
      surfaces in the near vicinity of buildings. Copper dispersion is discussed in
      terms of total copper flows, copper speciation and bioavailability at the
      immediate release situation, and its changes during transport from source to
      recipient. Presented results are based on extensive field exposures (eight years)
      at an urban site, laboratory investigations of the runoff process, published
      field data, generated predictive site-specific runoff rate models, and reactivity
      investigations toward various natural and manmade surfaces, such as those in
      soil, limestone, and concrete. Emphasis is placed on the interaction of copper
      containing runoff water with different soil systems through long-term laboratory
      column investigations. The fate of copper is discussed in terms of copper
      retention, copper chemical speciation, breakthrough capacities, and future
      mobilization based on changes in copper concentrations in the percolate water,
      computer modeling using the Windermere Humic Aqueous Model, and sequential
      extractions. The results illustrate that, for scenarios where copper comes in
      extensive contact with solid surfaces, such as soil and limestone, a large
      fraction of released copper is retained already in the immediate vicinity of the
      building. In all, both the total copper concentration in runoff water and its
      bioavailable part undergo a significant and rapid reduction.

PMID- 16566178
TI  - Nurses are not and never will be a fount of all knowledge.

PMID- 16566179
TI  - Campaigning nurses--the ethical dilemma.

PMID- 16566177
TI  - A new focus on caring principles.

PMID- 16566180
TI  - Continence crusaders.

PMID- 16566181
TI  - Risks and benefits associated with cosmetic procedures.
AB  - Cosmetic surgery is a rapidly growing area. This article examines what cosmetic
      surgery is, how prevalent the procedures are, risk management issues and how to
      ensure best practice.

PMID- 16566182
TI  - Marburg haemorrhagic fever.

PMID- 16566183
TI  - How to assess epidural blockade.

PMID- 16566184
TI  - Strategies for treating and managing testicular cancer.
AB  - Testicular cancer is a malignant neoplasm of the testis that carries an extremely
      favourable survival rate with current treatment strategies. This article
      discusses its aetiology, presentation, risk factors and diagnosis. Management
      strategies fall into two categories depending on subtype. Both are discussed for
      early and for late stage disease.

PMID- 16566185
TI  - Proton pump inhibitors.

PMID- 16566186
TI  - Implementing Essence of Care in a clinical research facility.
AB  - Since Essence of Care was introduced there have been a number of documents
      published on benchmarking in clinical areas. However, there is a lack of
      information on implementing the benchmarks in a research setting. This article
      describes how the Essence of Care framework has been translated for use at the
      Wellcome Trust Clinical Research Facility, detailing the implementation cycle,
      difficulties, achievements and future plans.

PMID- 16566188
TI  - Managing a caseload effectively.

PMID- 16566187
TI  - Addressing the concerns of the trainee nurse prescriber.
AB  - AIM: To identify the specialties from which trainee prescribers come and to
      determine their pre-training and post-training concerns about prescribing and how
      they are utilising their prescribing skills. METHOD: A self-report profile
      questionnaire including open and closed questions, some Likert-type scales and a
      24-item, self-report follow-up questionnaire were used. RESULTS: Half of the
      nurses who took part in this study came from four disciplines--practice nursing,
      mental health nursing, district nursing and paediatric/neonatal nursing. Before
      the course they were concerned that they had insufficient pharmacological
      knowledge to prescribe. However, once they had qualified this changed to concerns
      regarding educational needs, formal support and the way their role would be
      perceived by colleagues. Most participants felt that nurse prescribing impacted
      positively on patient care. CONCLUSION: With the right support systems in place,
      nurse prescribers are utilising their prescribing skills in order to develop
      their role, increase their clinical autonomy and improve the care of patients.

PMID- 16566189
TI  - Over one-quarter of nurses say they have been assaulted in the last year.

PMID- 16566190
TI  - [Otolaryngologic manifestations of Churg-Strauss sindrome. Report of a case and
      review of the literature].
AB  - Churg-Strauss Sindrome or allergic granulomatosis is a small vessel systemic
      vasculitis characterized by asthma, hypereosinophilia and necrotizing vasculitis
      with extravascular eosinophil granulomas. We describe a case assisted in our
      hospital who presented pulmonary infiltrates, fever, peripherical neuropathy,
      weight loss, myalgia, rhinosinusitis, with antecedents of nasal polyposis, and
      facial edema. Our aim is to review the main otolaryngologic manifestations of
      this rare illness that is treated with oral corticosteroids, immunosupresor drugs
      like ciclofosfamide and plasmapheresis.

PMID- 16566191
TI  - [Paraganglioma of the jugular foramen presenting with initial isolated vertigo].
AB  - The more common symptoms of the jugulotympanic paragangliomas are hearing loss,
      tinnitus and palsy of cranial nerves. Diagnosis is often delayed due to the slow
      growth of the tumour. We report one case with affectation of jugular foramen
      which clinically debuted as a peripheral vertigo and the diagnosis was made by
      CT, IRM and angiography. The patient was treated by Neurosurgery using Gamma
      Knife (radiosurgery) with good result.

PMID- 16566192
TI  - [Advantages of the determination of parathyroid hormone (PTH) intraoperatively in
      hyperparathyroidism surgery].
AB  - OBJECTIVE: To evaluate the utility of rapid or turbo intraoperative parathyroid
      (PTH) assay in the surgery of hyperparathyroidism. Since 2000 to july 2004 we
      have used this test on 39 patients. 24 of them corresponded to primary
      hyperparathyroidisms and 15 to secondary forms. Our results showed a PTH
      decreasing percentage >70% at 15 minutes in 92.3% of the cases. Only in two
      patients (5.1%) persisted the hypercalcemia after the surgery and one was
      reoperated with good clinic evolution. As advantages we stand out the reduction
      of surgical time, permitting unilateral parathyroid exploration instead a
      bilateral in primary HPT, and the prediction of success by confirming the
      excision of all hyperfunctionating parathyroid tissue in patients with multiple
      gland hyperplasia.

PMID- 16566193
TI  - [Postseptal orbital cellulitis and sinusitis. Descriptive study of 8 cases and
      literature review].
AB  - This is a retrospective study of 8 patients with postseptal orbital cellulitis
      (stages II-V of Chandler) caused by sinusitis during 1999-2003. The variables
      analyzed in this study included age, sex, delay in diagnosis, aetiology, imaging
      studies, microbiology specimens collected and treatment. Delays in diagnosis were
      frecuent. CT was the best radiologic study. Polymicrobial infections were the
      rule, including anaerobes. 4 patients of 8 needed surgical drainage. A general
      guideline for the management of periorbital and orbital cellulitis according to
      the clinical staging of the process is presented.

PMID- 16566194
TI  - [Pontine cavernous angioma (cavernoma) with initial ENT manifestations].
AB  - We report the case of a 22 years old female who consulted us for facial
      parestesias, hearing loss in right ear and sudden tinnitus. Her audiometry showed
      an unilateral discreet sensorineural hipoacusia and the cranial IRM, a mass of 20
      mm diameter in right pontine region and bulbus informed as cavernous angioma with
      signs of recent bleeding. The patient was sent to Neurosurgery but she refused
      the intervention. The risk of hemorrhage in the cavernomas is estimated at 0.25%
      to 1.6% per year and represents the main reason to advise a surgical treatment.

PMID- 16566195
TI  - [Prognostic value of the inmunohistochemical expression of protein p27KIP1 in
      laryngeal cancer].
AB  - In this paper we carried out an immunohistochemical study of protein p27KIP1
      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). In the cases with lymph node
      metastasis we also studied p27KIP1 expression at this level. Furthermore we have
      analysed the value of protein p27KIP1 expression as a prognostic factor (tumor
      recurrence, deads due to cancer and survival) and we evaluate the relationship
      between p27KIP1 expression and other clinic and pathologic parameters.

PMID- 16566196
TI  - [Suppurative bacterial acute parotitis in adults. Clinic and microbiological
      findings in 10 admitted patients].
AB  - We report the clinic and microbiological findings that were obtained in 10 adult
      patients admitted by our ENT Service with diagnosis of suppurative bacterial
      acute parotitis. S. aureus and Streptococcus sp were the most isolated organisms.
      All the patients were treated by hidratation, endovenous antibiotic therapy
      sometimes modified according to the antibiogram results, analgesics and
      antiinflammatories with success. In 3 times it was necessary to drain the
      purulent collection and in one of them there was a retroauricular abscess
      secondary to sialoadenitis.

PMID- 16566197
TI  - [Relationship between repeating tonsillitis and Berger's disease. Report of A
      case and review of the literature].
AB  - Berger's disease, so called IgA nephropathy, is a mesangioproliferative
      glomerulonephritis characterized by recurrent episodes of gross hematuria in
      relation with ENT infections like tonsillitis. We report a clinical case which
      presented that association and make a review of the literature about the possible
      advantages of tonsillectomy on the evolutive course and prognosis of the
      nephropathy.

PMID- 16566198
TI  - [Combined treatment of embolization followed by surgical resection in carotid
      paraganglioma].
AB  - Carotid body tumors represent a relatively uncommon finding in vascular surgery.
      We present the case of a 62 years old man with a right carotid paraganglioma
      diagnosed by cervical ultrasound scanner, magnetic resonance imaging and carotid
      arteriography. We decided to treat the patient in two times. In a first approach
      the tumor was percutaneously embolized, later on in a second time the
      paraganglioma was surgically resected. The patient is doing well without
      echographic evidence of tumor 3 years after the operation. This modality of
      treatment, embolization followed by surgical excision is a useful and valuable
      alternative.

PMID- 16566199
TI  - [Congenital hemangioma arising of internal orbitary edge. Importance of ENT
      exploration and treatment options].
AB  - Hemangiomas are the most common tumors in children. It id reported the case of 11
      months girl with congenital hemangioma at internal orbitary edge. ENT exploration
      is essential to rule out the affectation of nose and paranasal sinuses as well as
      other associated similar injuries in head and neck. As complementary tests we
      asked for CT and IRM to delimit the tumoration whose classic treatment are oral
      corticoids in high doses. Surgery usually is reserved for refractory cases to the
      medical therapy although the present exposition is changing due to different
      factors that we expose in the final discussion.

PMID- 16566200
TI  - [Malaria situation in the People's Republic of China in 2003].
AB  - Total 40,681 malaria cases and 129,147 suspected cases with 52 deaths were
      reported by the case reporting system in 910 counties of 21
      Provinces/Municipality/Autonomous Region (P/M/A) in 2003, and the annual
      incidence was 0.39/10000, an increase of 15.3% than that of the last year, which
      is the third year that malaria incidence consecutively increased since 2001.
      Based on a baseline survey in the project funded by the Global Fund to Fight
      AIDS, Tuberculosis and Malaria (GFATM), the estimated number of malaria cases was
      about 740,000 in 2003, 18 times more than reported. Among the 910 counties with
      reported malaria cases, 29 counties with an incidence more than 10/10000
      distributed in Yunnan (17 counties), Hainan (9), Anhui (1), Hubei (1) and Henan
      (1). There were 69 counties in which the malaria incidence was between 1/10000
      and 10/10000. The number of Plasmodium falciparum malaria cases was 4727,
      accounting for 11.6% of the total cases, of which 13.1% (621) were imported cases
      reported in 107 counties/cities of 16 P/M/A. Indigenous falciparum malaria was
      found in 78 counties/cities of Yunnan and Hainan Provinces, of which 64
      counties/cities were in Yunnan, increased by 22, 14 counties/cities were in
      Hainan, decreased by 2 compared to that of 2002. Yunnan and Hainan are stil the
      relatively high transmission areas. Yunnan has ranked No. 1 in the country in
      terms of the number of cases while Hainan ranked No. 1 by malaria incidence in
      recent years. 21,788 malaria cases were reported from the two provinces in 2003,
      accounting for 53.6% of the total reported cases in the country. There were 15
      431 cases with 43 deaths reported from Yunnan, the incidence was 4.24/10000, with
      an increase of 26.3% than that in the last year. Among the reported cases, 3529
      were falciparum malaria, increased by 22.9% in comparison to 2002. The number of
      reported cases in Hainan was 6357, with an incidence of 7.94/10000, 19.6%
      increase than the last year. In central China, the re-emergence of malaria was
      considerable in provinces along the Huai River, especially in Anhui Province. It
      should be stressed that the proportion of malaria cases was increasing in
      Anopheles sinensis transmitted areas where malaria was almost under control in
      the 1990s. The number of malaria cases in Anhui has been the second largest in
      the country since 2001. 8025 malaria cases and 18533 suspected cases were
      reported from Anhui in 2003, accounting for 19.7% of the total cases in the
      country, with an incidence of 1.53/10000 increased by 59.4% than that in 2002.
      Hubei Province reported 5 334 malaria cases with an incidence of 1.2/10000,
      increased by 33.3%. The number of reported cases in Henan and Jiangsu Provinces
      was 2 448 and 638 and the incidence decreased by 24.1% and 12.7% respectively.
      Focal outbreaks occurred in 222 villages of 9 counties in Anhui, Hubei and
      Jiangsu, where Anopheles sinensis is the principal transmission vector. Malaria
      cases reported from the above 4 provinces accounted for over 40% of the national
      figure. Cases reported from other P/M/A in the South and East China occupied
      about 6% of the total with certain degree of decrease, several hundreds from each
      of Guizhou, Guangxi, Sichuan, Guangdong, Fujian, Chongqing, Zhejiang, Shanghai
      and Hunan, more than 50% of which were imported cases. Less than 100 cases were
      reported from each of Shandong, Jiangxi, Liaoning, Shaanxi, Shanxi and Gansu
      Provinces in 2003. In summary, malaria is still an important problem of public
      health in China, especially in the southern and central parts where the incidence
      has been increasing since 2001. Yunnan and Hainan still faced critical situation
      of malaria endemics with a spread of Plasmodium falciparum, especially in the 25
      border counties in Yunnan. In the central part of the country including Anhui,
      Hubei, Henan and Jiangsu, where Anopheles sinensis was the principal vector, the
      malaria prevalence was highly unstable with frequent focal outbreaks in areas
      along the Huai River, which revealed new challenges to the malaria control
      program in China. Meanwhile, opportunities also exist with the support of the
      GFATM and the government, the latter paid much closer attention recently to
      issues in relation to public health.

PMID- 16566201
TI  - [Screening and preliminary identification of mimetic peptides of Plasmodium
      falciparum-infected erythrocyte membrane surface protein 1].
AB  - OBJECTIVE: To screen and identify mimetic peptides of Plasmodium falciparun
      infected erythrocyte membrane surface protein 1 in order to explore anti-adhesive
      agent against cerebral malaria. METHODS: Phage-borne peptide KLYLIAEGSVAA was
      used as panning targets to select target binders in a disulfide-constrained
      heptapeptides library. Three rounds of biopanning were carried out and then ELISA
      and competitive ELISA were used to evaluate the binding character between phage
      borne peptides and ICAM-1. The insert DNA sequences of positive clones were
      determined and their amino acid sequences were deduced. RESULTS: After three
      round panning, 22 clones were randomly chosen from the third panning and
      analyzed. Three clones showed positive interaction with ICAM-1, and two of them
      possessed the amino acid sequence C-ITAVPVR-C, the other one was C-DIMGGYN-C.
      These peptides specifically inhibited the binding of 15.2 antibody to ICAM-1
      detected by competitive ELISA. CONCLUSION: Two kinds of mimetic peptides of PfEMP
      1 have been obtained, which can bind with ICAM-1 specifically.

PMID- 16566202
TI  - [Microarray DNA chip in analyzing the association between HLA-DRB and advanced
      hepatosplenic schistosomiasis].
AB  - OBJECTIVE: To explore possible associations between host polymorphism of HLA
      class II genotypes and advanced hepatosplenic schistosomiasis japonica. METHODS:
      45 advanced schistosomiasis patients (experimental group) and 44 age- and sex
      matched patients with chronic schistosomiasis (control group) from the same area
      were investigated for their HLA class II gene DRB genotypes by genotyping the
      alleles using microarray DNA chip. The correlation of allele frequencies to
      advanced hepatosplenic schistosomiasis was compared for the two groups. RESULTS:
      HLA-DRB1*04x exhibited markedly higher frequency in advanced patients than that
      in control group (P < 0.01, RR = 3.928). In contrast, the frequency of HLA
      DRB1*15x in advanced patients was much lower when compared with that in control
      group (P < 0.01, RR = 0.050). Besides, the significant allele HLA-DRB1*15x
      displayed concurrence with allele DRB5*010x/020x. The linked gene haplotype
      DRB1*15x-DRB5*010x/020x showed significantly higher incidence in control group
      than in experimental group (P < 0.01). CONCLUSION: Allele HLA-DRB1*04x is
      positively, while HLA-DRB1*15x is negatively, correlated with advanced
      hepatosplenic schistosomiasis.

PMID- 16566203
TI  - [Mixed infection of Plasmodium malariae and Plasmodium falciparum].

PMID- 16566204
TI  - [Linking quantitation of electrophoresis pattern and data analysis in AFLP for
      Oncomelania hupensis].
AB  - OBJECTIVE: To search into a method for analyzing the quantitative data in
      amplified fragment length polymorphism (AFLP) electrophoresis. METHODS:
      Oncomelania snails collected from the field were screened. Forty snails found
      uninfected with schistosomiasis were divided randomly into two groups and used to
      isolate genomic DNA. AFLP electrophoresis pattern was first transformed into
      quantitative data by Glyko BandScan software, and the bands were read according
      to different standards of band-reading to acquire the corresponding data. These
      data sets were analyzed by genetic statistics to get an inference set, and the
      analysis of this inference set was performed to reach a summary description.
      RESULTS: The results of genetic variation from different standards of band
      reading were different With the increase of the standard value of band-reading,
      the indices indicating the genetic polymorphism of Oncomelania hupensis
      population (e.g. Shannon's information index) also increased. When the standard
      value reached at certain level, the values of these indices began to decrease.
      Compared with the above indices, the change for gene flow turned out contrary to
      the genetic identity. The distributions of inference results from different
      standards of band-reading all showed significant normal distribution. The mean
      value of genetic variation based on total grey was very close to that on the
      proportion of total grey. The average genetic identity between the
      "subpopulations" was 0.956 according to proportion of total grey or 0.958 from
      the total grey with an average genetic distance between the "subpopulations" of
      0.045 and 0.043 respectively. CONCLUSION: It seems to be a reasonable and
      accurate method by quantifying the AFLP electrophoresis pattern followed by
      analyzing the data through the use of the different standards of band-reading.

PMID- 16566205
TI  - [Studies on effect enhancement of the Schistosoma japonicum DNA vaccine pVIV02
      IL12-Sj23 by vegetal polysaccharides].
AB  - OBJECTIVE: To enhance the immunogenicity of the recombinant pVIVO2-IL12-Sj23
      vaccine of Schistosoma japonicum by using mixed vegetal polysaccharides as
      adjuvant. METHODS: The plasmid pVIVO2-IL12-Sj23 was constructed. 3 groups of
      BALB/C mice were injected intramuscularly with normal saline (Group A), pVIVO2
      IL12-Sj23 plasmid DNA (B), and pVIVO2-IL12-Sj23 plus mixed vegetal
      polysaccharides (C) respectively, and challenged with S. japonicum cercariae on
      the 4th week after immunization. Mice were killed to calculate the worm reduction
      rate and egg reduction rate in liver tissue on the 6th week after infection.
      Before and 4 weeks after immunization blood samples were collected. RESULTS: The
      worm reduction rate and egg reduction rate were 64.3% and 79.9%, respectively in
      group C, 45.5% and 58.4%, respectively in group B, showing a remarkable
      difference hetween them (P < 0.05). ELISA analysis showed a significantly higher
      level of IgG specific for Sj23 4 weeks after vaccination in groups B and C (P <
      0.05). However, there was no significant difference in IgG level between groups C
      and B (P > 0.05). CONCLUSION: When mixed vegetal polysaccharides are used as
      adjuvant, the effect of the vaccine pVIVO2-IL12-Sj23 can he considerably
      enhanced.

PMID- 16566206
TI  - [In vitro killing activity of the fractional proteins from microtus fortis serum
      to Schistosoma japonicum juveniles].
AB  - OBJECTIVE: To explore the killing effect of different fractional proteins from
      Microtus fortis (Mf) serum to S. japonicum juveniles, and to find possible
      association of the proteins with the natural resistance to schistosome infection.
      METHODS: The proteins in Mf serum were separated by means of ion-exchange column
      chromatography and molecular sieve column chromatography. After desalted by
      dialysis and lyophilized, the proteins were dissolved in DMEM medium which
      contained 300 U/ml penicillin and 300 microg/ml streptomycin, and the two-day old
      schistosomula were added in for in vitro cultivation (100 +/- 20/well). The
      killing activity of the fractional proteins to the juvenile worms was defined by
      mortality rate. RESULTS: 58 fractional proteins were separated from Mf serum, in
      which six proteins were confirmed to have a significant killing activity to
      schistosomula. The mortality of schistosomula all reached 37% and above, and the
      highest mortality (87.5%) was observed in the fraction 18.1, while the negative
      control was 25.09% (P < 0.01). CONCLUSION: Some fractional proteins in Microtus
      fortis serum show an effect in the natural resistance to schistosome infection.

PMID- 16566207
TI  - [Mathematical model in prediction and evaluation of the effects on control
      measures for schistosomiasis].
AB  - OBJECTIVE: To carry out a theoretical research on the rule that a mathematical
      model may play on predicting and evaluating the control effect of schistosomiasis
      japonica. METHODS: Earbour's two-host model was used to predict and evaluate the
      effect of different control measures by computer simulation. Pilot samples in two
      villages of Shanghai suburb in 1950s were applied for the analysis. RESULTS: When
      the prevalence was high, synchronous chemotherapy for human and cattle
      populations quickly reduced the indices of the infection. Mollusciciding provided
      positive impact on the effect of chemotherapy. Added with the environmental
      measures for snail control, the basic reproductive rate (BRR) and equilibrium
      prevalence in human and bovines were sustainably reduced and even reached an
      interruption of transmission. The effect of chemotherapy could be consolidated by
      the anti-fecundity vaccine for bovines. Satisfied control effect could also be
      obtained by chemotherapy in human and bovines combined with behaviour
      intervention for human and vaccination for bovines without snail control. In
      areas with lower levels of transmission velocity, BRR and prevalence, the effect
      of various interventions was better than that obtained in areas with higher
      levels of the above three infection indices, and the disease control could be
      easier. Conclusion The Barbour's mathematical model can be used to roughly
      predict and evaluate the effects of schistosomiasis control measures.

PMID- 16566208
TI  - [Paragonimus eggs in thyroid].

PMID- 16566209
TI  - [Cloning and expression of the fused gene of rhoptry protein ROP2 and major
      surface protein P30 from Toxoplasma gondii].
AB  - OBJECTIVE: To clone and express the fused gene fragment coding rhoptry protein
      ROP2 and major surface protein P30 from Toxoplasma gondii as a preparation for
      the construction of the complex ROP2-P30 antigen by gene engineering. METHODS:
      The gene fragment encoding P30 was amplified by PCR from T. gondii RH strain and
      subcloned into the recombinant plasmid pUC119/ROP2 already constructed. The
      recombinant plasmid pUC119/ROP2-P30 was digested by Sac I/HindIII and inserted
      into the same site of expression vector pET28b. The recombinant plasmid of
      pET28b/ROP2-P30 was transformed to E. coli and expressed under the induction of
      IPTG. RESULTS: The gene fragment 700 bp encoding P30 was obtained from the total
      DNA of T. gondii by PCR. The recombinant plasmid pET28b/ROP2-P30 was successfully
      constructed, which was highly expressed in E. coli, a fusion protein with
      molecular weight of 69000. CONCLUSION: The fusion gene encoding the rhoptry
      protein ROP2 and the major surface protein P30 of T. gondii has been successfully
      cloned and expressed to be an expected recombinant fusion protein ROP2-P30 with
      molecular weight 69000.

PMID- 16566210
TI  - [Expression and purification of Toxoplasma gondii GRA4 gene in prokaryotic
      system].
AB  - OBJECTIVE: To construct a prokaryotic expression system containing the dense
      granule protein 4 (GRA4) of Toxoplasma gondii, purify the expressed protein and
      detect its immunogenicity. METHODS: The specific fragment of GRA4 gene was
      amplified by PCR. After subcloning the prokaryotic expression recombinant pET
      GRA4, the expressed product was purified with His Bind affinity chromatography
      and analyzed by Western blot. BALB/c mice were immunized with the GRA4
      recombinant protein, and the antibody IgG titer was detected by ELISA. RESULTS:
      The pET-GRA4 prokaryotic expression system was obtained. The MW of the expressed
      protein was Mr 40,000 and formed in inclusion body. After purification, the
      recombinant protein could be specifically recognized by the T. gondii infected
      rabbit serum. Mice immunized with the purified recombinant protein elicited high
      titer of IgG antibody. CONCLUSION: The pET-GRA4 recombinant protein was
      successfully expressed and purified, which shows the immunogenicity.

PMID- 16566211
TI  - [Isolation and purification of an inhibitor on platelet aggregation from Ixodes
      sinensis].
AB  - OBJECTIVE: To study the bioactive components in ticks which inhibit platelet
      aggregation, and to understand the molecular mechanism of tick-host interaction.
      METHODS: Sephadex G-50 gel filtration and high performance liquid chromatography
      (HPLC) were used to purify the platelet aggregation inhibitor from lxodes
      sinensis. Its molecular weight and purity were checked by matrix-assisted laser
      desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Platelet-rich
      plasma (PRP) of rabbit was used to examine the function of platelet aggregation
      inhibitor. RESULTS: A purified platelet aggregation inhibitor was identified from
      L. sinensis with a molecular weight of 8 065. It inhibited platelet aggregation
      induced by ADP with strong potency. The inhibition of platelet aggregation
      reached over 90% under a concentration of 10 microg/ml. CONCLUSION: An inhibitor
      of platelet aggregation from L. sinensis was identified, which may play an
      important role for ticks to successfully get blood meal from their hosts.

PMID- 16566212
TI  - [Stomach perforation due to infection of Gnathostoma doloresi].

PMID- 16566213
TI  - [The relationship between infestation of Demodex folliculorum and epidermal
      neoplasm on face].
AB  - OBJECTIVE: To discuss the relationship between infestation of Demodex
      folliculorum and facial epidermal neoplasm. METHODS: A retrospective analysis was
      made with the pathological data of 153 cases collected in the recent four years
      on facial basal cell carcinoma, squamous cell carcinoma, seborrheic keratosis and
      trichilemmoma. The infection rate of Demodex folliculorum in the four types of
      neoplasm was evaluated and the relationship between the infection rate and the
      location of neoplasm and age was analyzed by V2 test. RESULTS: There was a
      significant difference in the infestation rate of Demodex folliculorum in the
      four types of epidermal neoplasm(P < 0.05), with the highest rate in basal cell
      carcinoma(56%), compared with seborrheic keratosis (21%), trichilemmoma (20%),
      and squamous cell carcinoma (14%). The infestation rate of Demodex folliculorum
      was significantly different in variant locations of epidermal neoplasm (P <
      0.05). The highest infestation rate was in cases of nasal neoplasm (71%),
      compared with other parts. In addition, among twelve cases of Demodex
      folliculorum positive nasal neoplasm, nine were basal cell carcinoma; ten of
      thirty-six basal cell carcinoma occurred on nose. CONCLUSION: The highest
      infestation rate of Demodex folliculorum was in cases of nasal epidermal neoplasm
      compared with other locations, and the cases of basal cell carcinoma showed the
      highest infestation rate among the four types of neoplasm.

PMID- 16566214
TI  - [Subcutaneous sparganosis: biopsy report of four cases].

PMID- 16566215
TI  - [Cloning and characterization of p43 cDNA from Trichinella spiralis].
AB  - OBJECTIVE: To clone and characterize the p43 cDNA from muscle larvae cDNA library
      of Trichinella spiralis (Ts) Chinese isolate. METHODS: PCR technique was used to
      amplify the target cDNA from muscle larvae cDNA library. After cloned in pMD18T
      vector, it was transformed into E. coli NovaBlue. The positive clones were
      sequenced and the cDNA was cloned into pET28a expression vector. After induced by
      IPTG, the inclusion body of the recombinant protein was purified and re-natured.
      The deoxyribonuclease II (DNase II) activity of the recombinant protein was
      tested by hydrolyzing XDNA. RESULTS: Open reading frame (ORF) of the p43 cDNA was
      successfully cloned from the muscle larvae cDNA library of the Chinese Ts, there
      were mutations of two nucleotides in the ORF of the Chinese Ts p43 cDNA comparing
      with that from U.S.A. isolate at the positions 210 and 604, namely, C and A in
      the USA isolate but T and G in the Chinese isolate. Considering that three
      authors had cloned the same p43 cDNA from the USA isolate and six groups
      (including this team) had also obtained the same sequence from the Chinese
      isolate, the mutation of the two nucleotides was considered as the single
      nucleotide polymorphic (SNP) marker of the Chinese Ts isolate. The DNase II
      activity of the recombinant protein was successfully detected by hydrolyzing
      lamdaDNA. CONCLUSION: The p43 cDNA was successfully cloned from the muscle larvae
      cDNA library of the Ts Chinese isolate. Two SNPs were found in the nucleotide
      sequence. The DNase II activity was proved.

PMID- 16566216
TI  - [RNA interference to the expression of peroxiredoxin-related genes in Trichomonas
      vaginalis].
AB  - OBJECTIVE: To inhibit the expression of the target genes of peroxiredoxin (Prx)
      and thioredoxin reductase (TrxR) by RNA interference and evaluate its effect on
      the growth of Trichomonas vaginalis. METHODS: Genomic DNA was extracted from
      cultured Trichomonas vaginalis with phenol-chloroform method and was transcribed
      to double stranded RNA (dsRNA). Short interference RNAs (siRNA, 21-23 bp)
      synthesized by digestion of dsRNA with RNase III and purified through filter
      cartridge, were transfected into the cells in three groups (A, B and C) to
      degrade the target genes of Prx, TrxR and Prx+TrxR through siPORT lipid,
      respectively, and the untransfected was selected as a control (group D). The
      levels of Prx and TrxR mRNA were determined 24 h and 48 h post-transfection by
      relative quantitative RT-PCR, and the growth of Trichomonas vaginalis was
      estimated under microscope 36 h post-transfection. RESULTS: Trichomonas vaginalis
      mRNA levels of Prx and TrxR decreased. Though the cell activity showed no
      significant difference (P > 0.05) in four groups as expected, a difference
      existed (P < 0.01) between the groups in the average of vells (7.2 x 10(7)/L,
      14.2 x 10(7)/L, 3.8 x l0(7) L and 20.3 x 10(7)/L in groups A, B, C and D
      respectively). CONCLUSIONS: RNA interference inhibits the expression of the genes
      of Prx and TrxR and extended Trichomonas vaginalis cells cycle considerably, but
      showed no influence on the cell activity.

PMID- 16566217
TI  - [Expression of hepatic Bcl-2 and Bax proteins in schistosome-infected mice and
      the role of pentoxifylline].
AB  - OBJECTIVE: To study the expression of hepatic Bcl-2 and Bax proteins in mice
      infected with Schistosoma japonicum and the role of pentoxifylline (PTX) in the
      expression. METHODS: Forty mice were randomly divided into 4 groups: one normal
      control group,mice in the other three groups were all infected each with 25
      cercariae, the infected control group was fed for 10 weeks after infection, and 2
      weeks after infection, the high dose PTX group was given PTX 360 mg/(kg x d) for
      8 weeks and the low dose PTX group was given PTX 180 mg/(kg x d)also for 8 weeks.
      At the end of 10 weeks all the mice were killed. Bcl-2 and Bax proteins
      expression was detected by immunohistochemisty. RESULTS: Compared with the normal
      control group, the expression of Bcl-2 and Bax was significantly higher in the
      infected control group (P < 0.05). Bcl-2 was significantly higher in high (dose
      PTX group than in the infected control group and in low dose PTX group (P <
      0.05). However there was no significant difference in the expression of Bax among
      the groups (P > 0.05). CONCLUSION: PTX treatment can significantly increase the
      expression of Bcl-2 in liver tissue of schistosome-infected mice in a dose
      dependent manner, and may play a role against liver inflammation and
      schistosomiasis-related liver fibrosis.

PMID- 16566218
TI  - [Experimental infection of mice with Blastocystis hominis].
AB  - OBJECTIVE: To seek a better pathway and proper number of parasites for
      Blastocystis hominis (B.h) infection in normal and immunocompromised ICR mice.
      METHODS: (1) 10(4), 10(5) and 10(6) B.h, cultured in RPMI 1640 medium from 3
      generations were used to infect mice through oral and rectum; (2) 10(6) B.h were
      used to infect immunocompromised mice through rectum. The reproduction of B.h in
      gastrointestinal tract and the pathologic changes in the tissues were observed.
      RESULTS: Mice were infected by B.h through either oral or rectum. The infected
      immunocompromised mice showed slow locomotion, depressed, lethargy, and descended
      body weight. Some infected mice discharged mucus feces, a few of them died during
      the experiment. Parasites were found in the whole gastrointestinal tract. Severe
      edema, hyperemia and congestion were observed in the tissues of jejunum, ileum,
      cecum and colon. The epithelia of small intestine and colonic mucous membrane
      showed exfoliation, inflammatory cell infiltration in submucosa, and structural
      changes in glands. CONCLUSION: Mice were more susceptible to Blastocystis hominis
      infection through rectum than orally. The parasites can be found in the whole
      gastrointestinal tract of mice, and can breed rapidly and cause significant
      pathological change in the gastrointestinal mucosa in immunocompromised mice.

PMID- 16566219
TI  - [Development of immunoblot kit for the detection of anti-Toxoplasma antibodies].
AB  - OBJECTIVE: To develop a diagnostic kit for the detection of anti-Toxoplasma
      antibodies in human sera by immunoblot technique. METHODS: The cytoplasm proteins
      of Toxoplasma gondii were extracted from collected ascites in Kunming strain mice
      infected by tachyzoites of Toxoplasma gondii (RH strain). Toxoplasma gondii
      soluble antigens were separated by SDS-PAGE electrophoresis and transferred to
      pyroxylin membrane. Using nonpoisonous tetramethylbenzidine (TMB) as horseradish
      peroxidase substrate for immunoblot, the optimal experimental conditions were
      selected through comparison of antigen preparation, reagents for blocking or
      washing, dilution concentration, reaction time, and frequencies of reacting band.
      Sensitivity, specificity, Youden index and stability were evaluated as the
      standard for the kit. RESULTS: In 30 sera with anti-Toxoplasma [gM antibodies and
      28 with IgG antibodies, the sensitivity for IgM and IgG antibody detection was
      90.0% (27/30) and 85.7% (24/28) respectively, the specificity was all 100% in
      examining 40 healthy control sera, and the Youden index was 0.9 and 0.86
      respectively. The kit was stable at 49 degrees C for 6 months. CONCLUSION: The
      immunoblot kit shows an easy operation, fast reaction and reliable result, and
      may be practical.

PMID- 16566220
TI  - [Epidemiological survey on hydatid disease in human in Yushu County].

PMID- 16566221
TI  - [A micro-culture method for continuous observation of free-living amoebae].
AB  - OBJECTIVE: To establish a method for co-culture of amoebae and endosymbionts,
      also for continuously observing the microphenotype of amoebae. METHODS: 24 wells
      culture plate with cover glass on the wells was used as containers. Amoebae and
      Candida albicans were co-cultured in microdrop of medium in the wells at 37
      degrees C, and observed under x1000. RESULTS: Continuous observation revealed
      trophozoites in various shapes like letters T, K, or Y, their movement and
      ingestion phenomenon were observed. CONCLUSION: The micro-culture method is
      useful in observing the amoebal morphology and its phagocytic process to Candida
      albicans.

PMID- 16566222
TI  - [Epidemiological study on taeniasis and cysticercosis in Rongshui County].

PMID- 16566223
TI  - [Two cases of angiostrongyliasis cantonensis].

PMID- 16566224
TI  - [An epidemiological analysis on malaria in Linzhi district of Tibet in 1986
      2004].
AB  - OBJECTIVE: To investigate the epidemiological characters of malaria in Linzhi
      district of Tibet. METHODS: A retrospective analysis on the epidemiology of
      malaria was carried out using the data on malaria situation in Linzhi district of
      Tibet in 1986-2004, referring to the distribution of season, population and
      region. RESULTS: The accumulative number of malaria cases in the period of 1986
      2004 was 2459. The annual incidence of malaria in the district was reduced from
      2.44 per ten thousand in 1986 to 1.03 per ten thousand in 2004, declined by 57.8%
      in 17 years. 99.3% of the cases were reported from Motuo County which was a
      typical high endemic area of malaria. The peak of prevalence occurred in June
      October and 66.7% of the total cases were in the age group of 15-59 years old.
      81.0% of the cases were farmers and 90.0% were Menba nationality. CONCLUSION:
      Motuo County has been the major area of malaria endemic in Linzhi district of
      Tibet. Most malaria cases in other counties are imported from Motuo.

PMID- 16566225
TI  - [Composition and diversity of acaroid mite community in different environments in
      Huainan City].
AB  - OBJECTIVE: To investigate the composition and diversity of acaroid mite community
      in Huainan City. METHODS: Dust samples were collected from storage circumstances,
      human dwellings and working places. Acaroid mites were isolated, counted and
      identified. 30 sampling spots from each of the three environments were selected,
      and 2 samples, each with 10 g, were collected from each sampling spot. RESULTS:
      26 species of acarid mites were identified from the three environments. These
      acarid mites belonged to 19 genera, 7 families. Diversity analysis showed that
      the average breeding density ranged from 15.35 +/- 6.13 to 31.27 +/- 8.34, the
      number of species ranged from 11 to 14, the values of the species richness index
      Rmargalef for the three circumstances raged from 1.99 to 4.35, the species
      diversity index (Shannon-Wiener index) ranged from 2.27 to 3.13, and Pielou index
      ranged from 0.95 to 0.96. CONCLUSION: The composition and diversity of acaroid
      mite community in three different circumstances are different significantly,
      which might be relevant to temperature, humidity and human interference.

PMID- 16566226
TI  - [Development of the specific antibodies and diagnostic antigens of Schistosoma
      japonicum].

PMID- 16566227
TI  - [Research progress on molecular biology of allergen from dermatophagoides].

PMID- 16566228
TI  - [Sero-epidemiological investigation on trichinosis in Dehong Prefecture].

PMID- 16566229
TI  - [Effect of alkaloids from Sophora moorcroftiana on Echinococcus granulosus in
      mice].

PMID- 16566230
TI  - [Relationship between multiple roles and psychological well-being: considering
      the cognitive relatedness of roles].
AB  - The purpose of this study was to examine the relationship between multiple role
      involvement and psychological well-being. Multiple roles were hypothesized to
      enhance people's well-being through a buffering effect and through resource
      appropriation, but were also hypothesized to decrease well-being through resource
      depletion. This study also examined self-complexity since previous work suggested
      that cognitive relatedness among roles would have a stronger impact on
      psychological well-being than mere number of roles. Survey data from 272 college
      students were used, and the results of multiple regression analysis suggested
      that having more independent roles activates resource utilization across
      different roles, which enhances psychological well-being.

PMID- 16566231
TI  - [Effect of coping behavior with work-family conflict in dual-career couples].
AB  - This study was carried out to accomplish two purposes: one was to establish the
      scale to plot the behavior to cope with work-family conflict, and the other was
      to examine the process models of such coping behavior. Answers toward the
      anonymous questionnaire survey of dual-career couples, which covered 191 males
      and 211 females, were analyzed. Based on the result of a factor analysis, the
      coping behavior scale which is comprised of the following three factors was
      established: flexible role assignment between husband and wife, home role
      reduction, and home role fulfillment. It was found that the coping behaviors of
      flexible role assignment and home role fulfillment are provoked by work-family
      conflict, and exert influence on mental health and satisfaction levels with
      marriage and work. In addition, home role reduction has the buffering effect to
      lessen the influence of work-family conflict on satisfaction levels and mental
      health. Moreover, coping behavior process models show gender difference.

PMID- 16566232
TI  - [Vagueness and the directionality of verbal probability expressions: the
      properties of probability information and their effects on decision making].
AB  - We examined the relationship between two properties of verbal probability (VP)
      expressions, "vagueness" and "directionality", and investigated the effects of
      these properties on decision making. Vagueness is defined as its imprecise
      characteristic of uncertainty expressions in VP, whereas the directionality is
      communicative functions which cause one to focus on the occurrence or non
      occurrence of the target event described by VP. Experiment 1 contrasted a
      disagreement in the literature as to whether one can predict the directionality
      from vagueness properties, and our analyses resolved the conflict by showing the
      ineffectiveness of the vagueness in predicting the directionality. Experiment 2
      administered decision tasks involving VP and numerical translation tasks of VP.
      We discovered that the directionality affects only on decision tasks. The results
      of Experiments 1 and 2 indicated that the directionality is distinct
      characteristic from the vagueness of VP, and these properties affect decisions
      independently. Implications are discussed.

PMID- 16566233
TI  - [Investigation of the cognitive process in selection of stress coping behavior].
AB  - The purpose of this study was to explore the cognitive process in selection of
      stress coping behavior. Subjects were 182 undergraduate students, who were asked
      to answer the questionnaire about their own stress experience and coping
      behavior. Factor analysis showed that the cognitive process in selection of
      coping behavior included four factors: "Expectation of positive outcome",
      "Expectation of emotion regulation", "Selection of habitual coping", "Selection
      in the elimination". Regression analysis showed that the score of "Expectation of
      positive outcome" was negatively correlated with stress response, the score of
      "Selection in the elimination" was positively correlated with stress response.
      Furthermore, interaction between the individual differences of cognitive process
      and coping behavior was found. People who engaged in emotion-focused coping style
      with elimination thinking felt more stressful than the others.

PMID- 16566234
TI  - [Intention to serve the same company for long years and job satisfaction in
      Japanese workers].
AB  - The purpose of this study was to investigate the relation between intention to
      serve the same company for long years and job satisfaction in Japanese workers.
      Four hundred eighteen Japanese workers completed a questionnaire to assess
      intention to serve for long years and job satisfaction. Job satisfaction was
      measured by two scales. One scale was consisted of the items which were deviced
      in the preliminary study concerning satisfaction with the company, and the other
      was consisted of the items based on the Minnesota Satisfaction Questionnaire. A
      factor analysis on the former scale yielded four factors: fosterage by company,
      order in company, company's name recognition, and expansibility of company. A
      factor analysis on the latter yielded four factors: contribution and activity,
      recognition and benefits, supervision, and discretion on job. The multiple
      regression analysis showed that "expansibility of company" was the most important
      predictor of intention to serve for long years.

PMID- 16566235
TI  - [Image and familiarity of student counseling service and willingness to use the
      service].
AB  - The purpose of this study was to investigate the relationship between image and
      familiarity that college students had about student counseling service and their
      willingness to make use of the service. A questionnaire was administered to 421
      college students. Factor analysis of the image found two positive sides:
      helpfulness and support in crisis, and two negative ones: disadvantage and
      uneasiness. Men had an image that was higher on support in crisis and
      disadvantage than women. Women were more familiar with the service, but no sex
      difference was found in the willingness to visit it. First-year students were
      lower in terms of their familiarity, but no image differences were found among
      students of different years. Regression analysis of the willingness indicated
      that different predictors became significant, depending on the sex and year of
      the respondents. It was suggested that different information about counseling
      service should be disseminated, so as to maximize the willingness, depending on
      the sex and year of the students.

PMID- 16566236
TI  - [Experimental test of the ideal free distribution in humans: the effects of
      reinforcer magnitude and group size].
AB  - The ideal free distribution (IFD) theory describes how animals living in the wild
      distribute themselves between two different resource sites. The IFD theory
      predicts that the ratio of animals in the two resource sites is equal to the
      ratio of resources available in those sites. The present study investigated the
      effects of absolute reinforcer magnitude and group size on the distribution of
      humans between two resource sites. Two groups of undergraduate students (N = 10
      and N = 20) chose blue or red cards to earn points. The ratio of points assigned
      to each color varied from 1 : 1 to 4 : 1 across five conditions. In each
      condition, absolute reinforcer magnitude was varied. The generalized ideal free
      distribution equation was fit to the data obtained under the different magnitude
      and group size conditions. These results suggest that larger absolute reinforcer
      magnitude and smaller group size produce higher sensitivity to resource
      distribution.

PMID- 16566237
TI  - [What dimensions do young children's trait concepts have for peers?].
AB  - This study investigated what dimensions young children's trait concepts have for
      real peers at their nursery school. Teachers of nursery school rated children's
      personality characteristics in terms of each dimension of the Big Five, and
      children were selected who showed different behavioral characteristics in those
      the five dimensions. Five- and six-year-old children (26 participants: 14 boys
      and 12 girls) evaluated those selected peers' personality. It was found that
      young children made different evaluations between extroversion and the other four
      traits (agreeableness, conscientiousness, emotional stability, and intellect),
      and between agreeableness and intellect. The results suggested that young
      children's trait concepts have a dimension of extroversion, in addition to a
      general dimension of goodness-badness.

PMID- 16566238
TI  - [Analysis on the strategies of primary health care and health promotion through
      an empowerment theory].

PMID- 16566240
TI  - [Study of influences of social support and social networks on participation in
      periodic health examination of the elderly at home comparison of three regions
      with different social backgrounds].
AB  - PURPOSE: Periodic health examination are presumed to be important with respect to
      the well-being of aged individuals. The purpose of this study was to analyze the
      relationships between elderly at home accepting periodic health examination and
      their social support and social networks. METHOD: The survey was performed
      targeting so-called young elderly persons living at home in 3 regions in Hokkaido
      Prefecture, a large city (Sapporo), an ex-coalmining town (Yuubari) and a small
      farming town (Takasu). The study populations were asked about social support and
      social networks, and the Mantel-Haenszel method was applied to analyze the data.
      RESULTS: 1) Both males and females who received periodic health examination
      within the last one year (participants) were members of various groups, such as
      neighborhood societies, clubs for the elderly and so on, and were more interested
      in public magazines and political issues than those who had never received
      periodic health examination (non-participants). Elderly males who accepted
      periodic health examination were those who were interested in elections, who had
      a hobby, and who thought that life was worthwhile. 2) Both elderly males and
      females who accepted periodic health examination were those who had friends, and
      elderly males who accepted periodic health examination were those who had close
      relatives and who lived in a friendly neighborhood. 3) Elderly males who accepted
      periodic health examination were more likely to both receive and supply
      instrumental and emotional support in interaction with others.

PMID- 16566239
TI  - [Physical and psychological predictors for the onset of certification of long
      term care insurance among older adults living independently in a community a 40
      month follow-up study].
AB  - OBJECTIVE: To ascertain predictors for the onset of different levels of
      certification of long-term care insurance among older adults living independently
      in a community. METHODS: Out of all residents aged 65 years and over living in
      Yoita town, Niigata prefecture, Japan (n = 1,673), 1,544 persons participated in
      the baseline interview survey in 2000 (response rate, 92.3%). Among these
      participants, 1,229 persons (79.6% of responders) were ranked as level 1, based
      on the hierarchical mobility level classification. They were followed up for the
      subsequent 3 years and 4 months to see whether they continued without
      certification of long-term care insurance or suffered onset of a "mild level",
      certified as levels "needing support" and 1 for long-term care insurance, or a
      "severe level" as 2-5. The Cox proportional hazards model with a stepwise method
      was used to identify the most parsimonious combination of predictors for each
      type of long-term care insurance certification. RESULTS: Of those who were
      followed up, 1,151 persons showed no disability in basic activities of daily
      living (ADL) at baseline nor died before application for long-term care during
      the follow-up and thus served for analysis. 1,055 persons (91.7%) remained as "no
      event", but 49 (4.3%) and 47 persons (4.1%) had onset of the "mild level" and the
      "severe level" during the follow-up, respectively. The final model for prediction
      of the "mild level" in both genders included advanced age and poor walking
      ability (hazard ratio (HR) for either unable or with difficulty: 7.22[95% CI,
      1.56-33.52] in males and both unable and with difficulty: 3.28[95% CI, 1.28-8.42]
      in females). The final model for prediction of the "severe level" in both genders
      included advanced age and poor instrumental ADL (HR for < or = 4 marks: 3.74[95%
      CI, 1.59-8.76] in males and 3.90[95% CI, 1.32-11.54] in females). Severe
      cognitive decline was a predictor only for the "severe level" in males. A history
      of hospitalization during past 1 year and poor chewing ability were predictive
      only for the "mild level" in females. CONCLUSIONS: Among older adults living
      independently in a community, most predictors for subsequent onset of mild level
      certification of long-term care insurance, except for advanced age, may be
      controlled by preventive strategies. Evaluating effectiveness of programs for
      this purpose warrants further study.

PMID- 16566241
TI  - [Influence of time and sequence of vaccination on completion ratio].

PMID- 16566243
TI  - [Comparison of intensive and moderate individual life-style intervention programs
      for overweight or obese persons with fasting glucose levels of 95-125 mg/dl in
      Japan].
AB  - OBJECTIVES: There are considerable differences in individual health education
      programs for persons at high risk of type 2 diabetes between ordinary Japanese
      life-style modification programs and the Diabetes Prevention Program in the US,
      the former being relatively moderate and the latter more intensive. We therefore
      compared the effectiveness of intensive and moderate intervention, focusing on
      the frequency of individual educational classes. METHODS: The subjects were men
      and women aged 44-69 years living in Nishiaizu town, Fukushima prefecture in
      Japan. Their fasting plasma glucose concentration was between 95 and 125 mg/dl at
      health examinations conducted in 2002 or 2003. They also had a body mass index
      (BMI) of 23.0 or higher, a fasting plasma glucose concentration of 125 mg/dl or
      lower and a post-load plasma glucose concentration (2 h) of 199 mg/dl or lower in
      the 2004 survey. We assigned the subjects according to their residences to an
      intensive life-style intervention group (two education classes per month; n = 11)
      or a moderate intervention group (one education class per month; n = 14). The
      main outcome measure was the change in body weight after 6 months of
      intervention. RESULTS: The loss of body weight was -3.5 kg (P< .0001) in the
      intensive intervention group and -1.8 kg (P = 0.02) in the moderate group, and
      the net difference in body weight loss between the groups was -2.0 kg (95%
      confidence interval -4.0 to -0.05; P = 0.045) after adjustment for age, sex, and
      baseline body weight. BMI and subcutaneous fat area showed similar results. The
      post-load plasma glucose concentration (2 h) and other tested values showed no
      significant net change between the two groups. CONCLUSIONS: Intensive and
      moderate intervention both reduced body weight in overweight or obese persons at
      high risk of type 2 diabetes. The intensive intervention, two sessions of
      individual education classes per month, was significantly more effective than the
      moderate one for reducing body weight.

PMID- 16566242
TI  - [Production of a fall prevention exercise programme considering suggestions from
      community-dwelling elderly].
AB  - OBJECTIVES: A fall prevention exercise programme, which elderly persons could
      undertake in their home alone to maintain and improve leg muscle strength, body
      balance ability and flexibility, was developed. The programme consisted of number
      of movements from which the best were selected on the basis of participant
      evaluation. The purpose of this report is to document the actual contents and an
      examination of the effects of this exercise programme in elderly people. METHODS:
      A total of 551 elderly persons, aged 75 years and over, not needing the support
      of elderly care insurance in S town, Miyagi Japan, were the subjects of this
      study. An intervention area and a non-intervention area were set in the study
      region. In the intervention area, 85 elderly people of high-risk for falls were
      selected to perform a longitudinal intervention study for one year. The selection
      criteria were as follows: 1) Maximum walking speed slower than median value, 2)
      Falls had been experienced in the past year. Forty elderly persons (15 men and 25
      women) participated in the class. Thirty movements designed to improve
      flexibility, leg muscle strength, and body balance, and to prevent tripping were
      executed and evaluated. Effects of this intervention on participants in the fall
      prevention class were examined using a follow-up survey one year after the
      baseline survey. The outcome of the fall prevention exercise programme was
      measured in terms of incidence of falls. RESULTS: A final fall prevention
      exercise programme consisting of ten movements was produced by the intervention.
      In addition, seven movements using a chair were part of the exercise programme.
      METS of the exercise programme for students, leaders, and elderly persons were
      3.41 +/- 0.37, 3.16 +/- 0.47, and 3.08 +/- 0.4, respectively. The incidence of
      falls over one year of the participants in the class significantly decreased from
      48.4% at baseline survey to 25.8% at follow-up survey, but that of non
      participants did not change. One-leg standing times with eyes open of the female
      participants significantly extended from the baseline survey to the follow-up
      survey, but not that of non-participants. CONCLUSIONS: This result of
      intervention suggested that incidence of falls was decreased by the execution of
      the exercise programme in twelve sessions of fall prevention class and at home.

PMID- 16566244
TI  - Influence of artifacts and pass/refer criteria on otoacoustic emission hearing
      screening.
AB  - A screening device for otoacoustic emission (OAE) testing was evaluated via
      measurements of click evoked OAEs (CEOAEs) and/or distortion product OAEs
      (DPOAEs) obtained in normally hearing young adults and newborns. Moreover,
      measurements were performed in a passive cavity and in ears with severe
      sensorineural hearing loss, in which the occurrence of a pass result was assumed
      to indicate artifacts. Different parameter settings were investigated. In
      comparison to normally hearing young adults, overall pass rates in newborns were
      similar using CEOAEs (93 to 100%), but lower using DPOAEs (65 to 95% vs. 83 to
      100%). Pass rates in ears with severe hearing loss were 10% at 2 kHz, 13% at 3
      kHz, and lower at other frequencies. Pass rates in the test cavity were generally
      low. The influence of test frequency on pass rates and calculations using
      computer simulation indicated the presence of artifacts. The discrimination of
      such artifacts from biological signals is difficult or impossible, and they may
      represent a serious problem for efficient OAE screening.

PMID- 16566245
TI  - Bi-syllabic, modern Greek word lists for use in word recognition tests.
AB  - The development of a word recognition test for Modern Greek, which is comprised
      of three fifty-word lists, is described herein. The development was guided by
      four principles: (1) use of the shortest words possible (two syllables for Greek)
      (2) use of highly frequent words (3) phonetic balance and (4) appropriate balance
      of first and second syllable stress. The lists were recorded by one male and one
      female native speakers. Thirty-seven native speakers of Greek listened to all
      words by both speakers. Across lists, the mean correct identification score was
      97.9% for the female voice (95% confidence interval 96.97 to 98.84) and 96.5%
      (95% confidence interval 95.31 to 97.77) for the male voice. This small
      difference was statistically significant (p < .01) and concentrated on words with
      first syllable stress. In future work, these recordings can be used in adult
      tests of speech perception and can be modified for tests of central auditory
      processing.

PMID- 16566246
TI  - Auditory status of persons with intellectual disability at the German Special
      Olympic Games.
AB  - Among persons with intellectual disability, the prevalence of hearing impairments
      is high. During the German Special Olympics Summer Games 2004, a hearing
      screening was conducted on 755 athletes with intellectual disabilities.
      Obligatory screening included ear inspection and recording of otoacoustic
      emissions, and optional screening included tympanometry and brief pure-tone
      audiometry. 38.0% of the athletes failed the screening. 53.0% needed ear wax
      removal. 56.1% of the fails indicated sensorineural hearing loss and 13.6%
      indicated mixed hearing loss. 12.5% of the fails were caused by unremovable ear
      wax, 1.4% by ear canal affections, and 16.4% by middle ear problems. Left ear
      fails were more frequent than right ear fails. A peripheral hearing disturbance
      can thus be expected in every third subject. The high failure rate, a
      considerable percentage of previously undetected profound hearing loss (1.1%),
      and the frequent need for ear wax removal, suggest that nearly half of persons
      with intellectual disabilities need regular otological or audiological
      consultations.

PMID- 16566247
TI  - Modification of the Threshold Equalising Noise (TEN) test for cochlear dead
      regions for use with steeply sloping high-frequency hearing loss.
AB  - Steeply sloping high-frequency hearing loss is often associated with cochlear
      dead regions. These can be identified by measuring pure-tone thresholds in quiet
      and in Threshold-Equalising Noise (TEN). However, many patients cannot be
      adequately tested because the low frequencies in the TEN lead to uncomfortable
      loudness. We investigated the effect of high-pass filtering on the TEN-test
      results and the loudness of the TEN. Twenty-four normally hearing subjects and 35
      subjects with steeply sloping high-frequency hearing loss were tested, using the
      standard TEN (TENs), and TEN high-pass filtered at 0.5 kHz (TEN0.5) or 1 kHz
      (TEN1). For both groups, masked thresholds did not differ across noise types for
      frequencies above 1 kHz. Over 50% of the hearing-impaired ears tested met the
      criteria for a dead region at 4 kHz, using all three noise types. However, masked
      thresholds and the prevalence of positive TEN-test results at 1 kHz were both
      lower with the TEN 1. The TEN1 was judged the most comfortable noise by 68% of
      the hearing-impaired subjects. We conclude that high-pass filtering would allow
      testing at higher TEN levels for patients with steeply sloping hearing loss.

PMID- 16566248
TI  - The listening in Spatialized Noise test: normative data for children.
AB  - The Listening in Spatialized Noise test (LISN) produces a three-dimensional
      auditory environment under headphones, using only a PC and an audiometer, and was
      designed to provide an ecologically valid assessment of auditory figure-ground
      skills in children. The listener is required to indicate the intelligibility
      level of a story presented at 0 degree azimuth, in the presence of distracter
      sentences simultaneously presented at either 0 degree or +/- 90 degrees azimuth.
      Various measures assess the extent to which either spatial, vocal, or spatial and
      vocal cues combined, increase a listener's ability to comprehend the story,
      without being affected by differences between participants in variables such as
      linguistic skills. There was a trend of improved performance with increasing age
      for 48 normally hearing seven-, eight-, and nine-year-olds, and sixteen adults.
      Whereas some significant differences were found between adults and children,
      there were no significant differences in performance between the seven-, eight-,
      and nine-year-olds on any measure, and no significant gender or practice effects
      were observed. Future studies on children with suspected auditory processing
      disorder were considered warranted.

PMID- 16566249
TI  - Test accuracy and prognostic validity of multiple auditory steady state responses
      for targeted hearing screening.
AB  - The test accuracy and prognostic validity of Multiple Auditory Steady State
      Responses (MSSR) and click Auditory Brainstem Responses (cABR) was compared
      within the context of a targeted screening protocol. A sample of 508 high-risk
      babies was first screened using cABR and MSSR (500 and 2000 Hz). All children
      (failed/ pass) were called back at three to four years of age to determine their
      hearing status (pure-tone audiometry). Although both methods showed an equally
      good test performance in the first screen (sensitivity: 100% and specificity: 92
      95%), the MSSR may have some potential advantage to identify low-frequency
      hearing loss. Furthermore, the confirmatory audiometry with MSSR predicted the
      child hearing status more accurately than the cABR. In conclusion, the MSSR can
      provide valuable information for the diagnosis and management of infants earlier
      detected by a screening protocol and further developed might be also useful as a
      screening test.

PMID- 16566250
TI  - An apparatus for diagnosis of ossicular chain mobility in humans.
AB  - Confirmation of the conditions of the ossicles is essential for tympanoplasty.
      However, at present, ossicular mobility is experimentally estimated with
      palpation by a surgeon, and the results depend on the surgeon's skill. In this
      study, a new apparatus for quantitatively measuring ossicular mobility was
      developed. With this apparatus, the ossicles were displaced and the reaction
      force from the ossicles, (i.e. the load applied to the ossicles) was
      simultaneously detected. Ossicular mobility of three patients with otosclerosis
      or chronic otitis media was measured to evaluate the usability of the apparatus.
      The apparatus can distinguish the differences in ossicular mobility between
      normal and fixed ossicles, and it makes estimating the change of mobility between
      pre- and posttreatments for ossicular fixation possible. Positive correlation was
      seen between ossicular mobility and hearing level.

PMID- 16566251
TI  - E. P. Pope Memorial Award to Dr. Patricia C. Blanchard.

PMID- 16566252
TI  - Longitudinal study of ELISA seroreactivity to Mycobacterium avium subsp.
      paratuberculosis in infected cattle and culture-negative herd mates.
AB  - Two thousand nine hundred fifty-two serum samples, collected once or twice
      annually from 545 cows of known fecal culture status were tested for antibodies
      to Mycobacterium avium subsp. paratuberculosis using a commercially available
      enzyme-linked immunosorbent assay (ELISA) test. Overall, 13.5% of the samples
      from 282 infected cows had positive ELISA results, but when tested multiple
      times, 38.3% of the cows had at least 1 serum sample with positive results. Among
      263 fecal culture-negative cows, 98.1% of the serum samples had negative ELISA
      results, but when tested multiple times, 7.8% of the cows had at least 1 positive
      ELISA sample. Fecal culture was positive on a test before the first positive
      ELISA in 50 cows, ELISA was positive before fecal culture in 12 cows, and in 38
      cows, both tests became positive at the same testing time. An additional 174 cows
      were positive on fecal culture and always negative on ELISA until culled. For
      cows that had ELISA sample:positive (S/P) ratios below the cutoff point, the
      change in S/P between sequential tests was evaluated to determine whether a rise
      in S/P could predict infection status. In this study, change in S/P was not a
      useful predictor of infection status in seronegative cows.

PMID- 16566253
TI  - High throughput detection of bluetongue virus by a new real-time fluorogenic
      reverse transcription-polymerase chain reaction: application on clinical samples
      from current Mediterranean outbreaks.
AB  - A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was
      developed for the detection of bluetongue virus (BTV) in blood samples. A
      combination of primers specific for a highly conserved region in RNA segment 5
      (based on Mediterranean BTV sequences) and a DNA probe bound to 5'-Taq nuclease
      3' minor groove binder (TaqMan MGB) was used to detect a range of isolates. This
      real-time RT-PCR assay could detect 5.4 x 10(-3) tissue culture infectious doses
      (TCID50) of virus per milliliter of sample, which was comparable to our current
      BTV diagnostic nested RT-PCR assay. The assay detected all recent Mediterranean
      isolates (including serotypes 2, 4, and 16), BTV vaccine strains for serotypes 2
      and 4, and 15 out of the 24 BTV reference strains available (all serotypes), but
      did not detect the related orbiviruses epizootic hemorrhagic disease and African
      horse sickness viruses. Following assay evaluation, the ability of this assay to
      identify BTV in recent isolates (2003, 2004) from ovine and bovine samples from
      an epizootic outbreak in Spain was also tested. Minor nucleotide changes
      (detected by sequencing viral genomes) within the probe-binding region were found
      to have a profound effect on virus detection. This assay has the benefits of
      being fast and simple, and the 96-well format enables large-scale epidemiological
      screening for BTV, especially when combined with a high-throughput nucleic acid
      extraction method.

PMID- 16566254
TI  - Diseases and pathogens associated with mortality in Ontario beef feedlots.
AB  - This study determined the prevalence of diseases and pathogens associated with
      mortality or severe morbidity in 72 Ontario beef feedlots in calves that died or
      were euthanized within 60 days after arrival. Routine pathologic and
      microbiologic investigations, as well as immunohistochemical staining for
      detection of bovine viral diarrhea virus (BVDV) antigen, were performed on 99
      calves that died or were euthanized within 60 days after arrival. Major disease
      conditions identified included fibrinosuppurative bronchopneumonia (49%),
      caseonecrotic bronchopneumonia or arthritis (or both) caused by Mycoplasma bovis
      (36%), viral respiratory disease (19%), BVDV-related diseases (21%), Histophilus
      somni myocarditis (8%), ruminal bloat (2%), and miscellaneous diseases (8%).
      Viral infections identified were BVDV (35%), bovine respiratory syncytial virus
      (9%), bovine herpesvirus-1 (6%), parainfluenza-3 virus (3%), and bovine
      coronavirus (2%). Bacteria isolated from the lungs included M. bovis (82%),
      Mycoplasma arginini (72%), Ureaplasma diversum (25%), Mannheimia haemolytica
      (27%), Pasteurella multocida (19%), H. somni (14%), and Arcanobacterium pyogenes
      (19%). Pneumonia was the most frequent cause of mortality of beef calves during
      the first 2 months after arrival in feedlots, representing 69% of total deaths.
      The prevalence of caseonecrotic bronchopneumonia caused by M. bovis was similar
      to that of fibrinosuppurative bronchopneumonia, and together, these diseases were
      the most common causes of pneumonia and death. M. bovis pneumonia and
      polyarthritis has emerged as an important cause of mortality in Ontario beef
      feedlots.

PMID- 16566255
TI  - Naturally occurring Mycoplasma bovis-associated pneumonia and polyarthritis in
      feedlot beef calves.
AB  - Mycoplasma bovis is perceived as an emerging cause of mortality in feedlot beef
      cattle. This study examined the lesions and infectious agents in naturally
      occurring M. bovis-associated bronchopneumonia and arthritis and the relationship
      of this condition with bovine viral diarrhea virus (BVDV) infection. Standardized
      pathologic, immunohistochemical, and microbiologic investigations were conducted
      on 99 calves that died or were euthanized within 60 days after arrival in 72
      feedlots. Cranioventral bronchopneumonia with multiple foci of caseous necrosis
      was identified in 54 of 99 calves, including 30 with concurrent
      fibrinosuppurative bronchopneumonia typical of pneumonic pasteurellosis.
      Mycoplasma bovis was consistently identified in these lesions by culture and
      immunohistochemistry, but also commonly in healthy lungs and those with pneumonia
      of other causes. Focal lesions of coagulation necrosis, typical of pneumonic
      pasteurellosis, were often infected with both Mannheimia haemolytica and M.
      bovis. Arthritis was present in 25 of 54 (46%) calves with M. bovis pneumonia,
      and all calves with arthritis had pneumonia. BVDV infection was more common in
      calves with lesions of bacterial pneumonia than in those dying of other causes,
      but BVDV infection was not more common in calves with caseonecrotic
      bronchopneumonia than those with fibrinosuppurative bronchopneumonia.
      Retrospective analysis identified cases of M. bovis pneumonia in the early 1980s
      that had milder lesions than the current cases. The findings suggest that, in at
      least some calves, M. bovis induces caseonecrotic bronchopneumonia within the
      lesions of pneumonic pasteurellosis.

PMID- 16566256
TI  - Molecular and antigenic characterization of a Mycoplasma bovis strain causing an
      outbreak of infectious keratoconjunctivitis.
AB  - An unusually high incidence of infectious keratoconjunctivitis followed by
      pneumonia and arthritis was observed in beef calves of a managed herd. No
      Moraxella spp. or bacteria other than Mycoplasma spp. were obtained from
      conjunctival and nasal swabs. A strategy was designed for characterization of
      bovine mycoplasmas at species and strain level on the basis of a combination of
      molecular tools and the immunoblotting method. The strategy made it possible to
      rapidly assign the bacterium responsible for this outbreak to one of the
      phylogenetic clusters of bovine mycoplasmas delineated in this study and then to
      identify it as Mycoplasma bovis. The strain, designated Sar 1, showed a 100% 16S
      rDNA sequence identity with two European strains (120/81 and MC3386) isolated in
      Germany and Ireland, respectively, and hosts a vsp gene analog to the vspA,
      vsp422-4, and vsp422-8 genes of the M. bovis reference strain PG45T and of the
      field strain 422. The use of a cross-reactive rabbit serum developed against the
      Mycoplasma agalactiae immunodominant antigen P48 confirmed the molecular
      findings. The immunological response of calves against M. bovis was also
      investigated. This is the first report on the occurrence of M. bovis on the
      Island of Sardinia (Italy).

PMID- 16566257
TI  - Experimentally induced infection of reindeer (Rangifer tarandus) with
      Mycobacterium bovis.
AB  - In the USA, all species of Cervidae are included in the USDA's uniform methods
      and rules for the eradication of bovine tuberculosis and, therefore, are subject
      to regulations regarding intradermal tuberculin testing. In reindeer (Rangifer
      tarandus), infection with Mycobacterium bovis is exceedingly rare and the
      response of reindeer to infection with M. bovis in pathologic and immunologic
      terms is unknown. The objectives of the study reported here were to describe the
      pathologic changes associated with M. bovis infection in reindeer and evaluate
      the effectiveness of intradermal tuberculin testing as a means of diagnosis of
      tuberculosis in reindeer. Thirteen reindeer were inoculated intratonsilarly with
      10(5) colony-forming units (CFU) of M. bovis, and 4 noninoculated reindeer served
      as negative controls. The comparative cervical test (CCT) was done on all
      reindeer 90 and 240 days after inoculation. Thirteen months after inoculation,
      all reindeer were euthanized and examined. All experimentally inoculated reindeer
      developed lesions in the medial retropharyngeal lymph nodes. The CCT accurately
      identified all M. bovis-inoculated reindeer, but false-positive results were
      common among negative-control reindeer. Modifications of the method for
      interpretation of the CCT decreased false-positive results without increasing
      false-negative results. Reindeer are susceptible to infection with M. bovis;
      however, lesions are fewer in number, less severe in nature, and less widely
      disseminated than are those seen in white-tailed deer (Odocoileus virginianus).
      Comparative cervical skin testing of reindeer can be highly sensitive, but has
      low specificity. Specificity can be improved by modification of criteria for
      interpretation of the CCT.

PMID- 16566258
TI  - Comparative toxicosis of sodium selenite and selenomethionine in lambs.
AB  - Excess consumption of selenium (Se) accumulator plants can result in selenium
      intoxication. The objective of the study reported here was to compare the acute
      toxicosis caused by organic selenium (selenomethionine) found in plants with that
      caused by the supplemental, inorganic form of selenium (sodium selenite). Lambs
      were orally administered a single dose of selenium as either sodium selenite or
      selenomethionine and were monitored for 7 days, after which they were euthanized
      and necropsied. Twelve randomly assigned treatment groups consisted of animals
      given 0, 1, 2, 3, or 4 mg of Se/kg of body weight as sodium selenite, or 0, 1, 2,
      3, 4, 6, or 8 mg of Se/kg as selenomethionine. Sodium selenite at dosages of 2,
      3, and 4 mg/kg, as well as selenomethionine at dosages of 4, 6, and 8 mg/kg
      resulted in tachypnea and/or respiratory distress following minimal exercise.
      Severity and time to recovery varied, and were dose dependent. Major
      histopathologic findings in animals of the high-dose groups included multifocal
      myocardial necrosis and pulmonary alveolar vasculitis with pulmonary edema and
      hemorrhage. Analysis of liver, kidney cortex, heart, blood, and serum revealed
      linear, dose-dependent increases in selenium concentration. However, tissue
      selenium concentration in selenomethionine-treated lambs were significantly
      greater than that in lambs treated with equivalent doses of sodium selenite. To
      estimate the oxidative effects of these selenium compounds in vivo, liver vitamin
      E concentration also was measured. Sodium selenite, but not selenomethionine
      administration resulted in decreased liver vitamin E concentration. Results of
      this study indicate that the chemical form of the ingested Se must be known to
      adequately interpret tissue, blood, and serum Se concentrations.

PMID- 16566259
TI  - Assessment of some blood parameters as potential markers of hepatic copper
      accumulation in cattle.
AB  - The increasing frequency of copper (Cu) toxicosis episodes in cattle in recent
      years, mainly associated with excess Cu supplementation, underscores the need to
      identify animals in the clinically silent phase of hepatic Cu accumulation. The
      aim of the study reported here was to evaluate the suitability of various blood
      parameters as potential early markers of hepatic Cu accumulation in cattle.
      Paired liver and blood samples from 70 calves aged 6 to 10 months were obtained
      at slaughter in a region in northwestern Spain where animals usually have hepatic
      Cu concentration higher than safe values. Neither serum Cu concentration nor
      ceruloplasmin (CP) concentration, the 2 parameters most commonly used for
      diagnosis of Cu deficiency, were significantly associated with hepatic Cu
      concentration. However, whole-blood Cu concentration had a slight but significant
      correlation with hepatic Cu concentration (r = 0.269, P = 0.026). The use of
      calculated blood parameters, such as the serum or whole-blood non-CP Cu fraction,
      or the CP-to-serum Cu ratio, increased the correlation with the hepatic Cu
      concentration (r = 0.393, P = 0.001, in the case of whole-blood, non-CP Cu
      concentration), but the strength of the association remained insufficient for
      accurate prediction of hepatic Cu values. Likewise, hepatic enzyme (aspartate
      transaminase and gamma-glutamyltransferase) activities were significantly or
      nearly correlated significantly with hepatic Cu concentration, but the strength
      of the association remained too low for accurate prediction. It is concluded that
      direct analysis of Cu concentration in liver biopsy specimens--preferably
      postmortem liver samples obtained at slaughter--is the best technique currently
      available for detecting chronic subclinical Cu accumulation in cattle at risk for
      supraoptimal Cu exposure.

PMID- 16566260
TI  - Histochemical and immunohistochemical evidence of a bacterium associated with
      lesions of epizootic bovine abortion.
AB  - Epizootic bovine abortion (EBA), a tick-transmitted disease of pregnant cattle
      grazing foothill pastures, is a major cause of reproductive failure in California
      and adjacent states. Affected fetuses develop a chronic disease, resulting in
      late-term abortion or premature calving. Despite investigations spanning 50
      years, to the authors' knowledge, the etiologic agent of EBA has not yet been
      isolated from affected fetuses or the tick vector. The diagnosis of EBA is based
      on gross and microscopic lesions. Recently, documentation that the etiologic
      agent is susceptible to antibiotics and identification of a unique 16S
      deltaproteobacterial rDNA gene sequence in 90% of thymus tissues from aborted
      fetuses have supported the role of a bacterial infection as the cause of EBA. To
      determine whether bacteria could be detected in the tissues, histochemical
      staining and immunohistochemical procedures were used on formalin-fixed, paraffin
      embedded tissues. Use of a modified Steiner silver stain revealed small numbers
      of intracytoplasmic bacterial rods in 37 of 42 thymic samples from EBA-affected
      fetuses. Improved detection was achieved by use of immunohistochemical staining
      with serum from EBA-affected fetuses that resulted in detection of numerous
      bacterial rods in the cytoplasm of histiocytic cells in the thymus from all 42
      EBA-affected fetuses. Immunohistochemical examination of additional tissues from
      21 field and experimental EBA cases revealed positively stained intracytoplasmic
      bacterial rods in many organs with inflammatory lesions. Use of the modified
      Steiner stain and immunohistochemical staining of tissues from negative-control
      fetuses failed to reveal organisms. To the authors' knowledge, this is the first
      report to document morphologic evidence of a bacterium associated with the
      lesions of EBA.

PMID- 16566261
TI  - Detection of canine parvovirus in fecal samples using loop-mediated isothermal
      amplification.
AB  - Loop-mediated isothermal amplification (LAMP) is a novel, sensitive, and rapid
      technique for detection of genomic DNA. The end-product of the technique is a
      white precipitate of magnesium pyrophosphate that is visible without the use of
      gel electrophoresis. The LAMP method was applied to the detection of canine
      parvovirus (CPV) genomic DNA. A set of 4 primers, 2 outer and 2 inner, were
      designed from CPV genomic DNA targeting the VP2 gene. The optimal reaction time
      and temperature for LAMP were determined to be 60 minutes and 63 degrees C. On
      the basis of results for 50 canine fecal samples using polymerase chain reaction
      (PCR) analysis as the gold standard, the relative sensitivity of LAMP was 100%
      and the relative specificity was 76.9%. The detection limit of the LAMP method
      was 10(-1) median tissue culture infective doses (TCID50)/ml, compared with 10
      TCID50/ml for PCR analysis. In addition to the advantage resulting from visual
      detection of the end product, the LAMP method is very rapid, requiring only 1
      hour to complete. This assay would be a viable alterative to PCR analysis for
      diagnosis of CPV infection in dogs. The LAMP method holds promise for use as a
      diagnostic assay for CPV detection in a clinical setting.

PMID- 16566263
TI  - Reverse transcription-polymerase chain reaction on pooled samples to detect
      bovine viral diarrhea virus by using fresh ear-notch-sample supernatants.
AB  - Ear-notch samples from 3,599 yearling heifers were collected to detect
      persistently infected (PI) animals with suspect bovine viral diarrhea virus
      (BVDV). Individual immunohistochemistry (IHC), individual antigen-capture enzyme
      linked immmunosorbent assay (AC-ELISA), and reverse transcription-polymerase
      chain reaction (RT-PCR) tests with pooled ear-notch supernatants were compared
      with samples from 3,016 heifers, whereas RT-PCR ear-notch pools and individual AC
      ELISA tests were compared with samples from all 3,599 heifers. Four heifers were
      identified positive by both IHC and AC-ELISA, whereas the remaining heifers were
      identified negative by both tests. When supernatant from ear notches from 100
      animals was randomly pooled and RT-PCR was accomplished on each pool, RT-PCR
      identified 2 pools that contained 1 positive AC-ELISA sample and 1 pool that
      contained 2 positive AC-ELISA samples. Further evaluation of the pooled RT-PCR
      ear-notch supernatant detected 100% (n = 36) samples spiked with supernatant from
      a single randomly selected positive AC-ELISA ear notch. Although follow-up
      confirmatory tests were not completed, all 3 methods correlated 100% in detecting
      suspect PI animals, with a kappa value of 1. The use of RT-PCR on pooled ear
      notch supernatant could provide an initial, rapid, cost-effective method of
      screening cattle herds for BVDV PI animals. Subsequent serial testing with an AC
      ELISA to evaluate individual samples included in the positive pool could minimize
      the length of time other animals are exposed to the virus.

PMID- 16566262
TI  - Evaluation of antigen-capture ELISA and immunohistochemical methods for avian
      surveillance of West Nile virus.
AB  - Accurate detection of West Nile virus (WNV) in corvids is essential for
      monitoring the spread of virus during the mosquito season. Viremia in corvids is
      very high, with titers approaching 10(8) viral particles/ml. In the presence of
      such marked viremia, the sensitivity of real-time reverse transcription
      polymerase chain reaction (RT-PCR) analysis is unnecessary, and more cost
      effective methods should be assessed. To this end, antigen-capture ELISA (ACE)
      and immunohistochemical (IHC) assays were evaluated. Skin, cloacal swab
      specimens, and feathers from corvids were tested by use of ACE, and results were
      compared with results obtained from use of real-time RT-PCR analysis. Of the 3
      sample types, skin gave the best sensitivity (98%) and specificity (100%). Skin,
      brain, kidney, and spleen from corvids were analyzed by IHC, and results were
      compared with real-time RT-PCR results. Kidney and spleen were more often
      positive by use of IHC than were brain and skin tissue; however, IHC did not
      perform as well as ACE in the identification of virus-positive birds. Results of
      this study support the use of a skin sample in an ACE format as an effective
      surveillance method for corvids.

PMID- 16566264
TI  - Detection of foot-and-mouth disease virus: comparative diagnostic sensitivity of
      two independent real-time reverse transcription-polymerase chain reaction assays.
AB  - Rapid and accurate diagnosis is central to the effective control of foot-and
      mouth disease (FMD). It is now recognized that reverse-transcription polymerase
      chain reaction (RT-PCR) assays can play an important role in the routine
      detection of FMD virus (FMDV) in clinical samples. The aim of this study was to
      compare the ability of 2 independent real-time RT-PCR (rRT-PCR) assays targeting
      the 5' untranslated region (5'UTR) and RNA polymerase (3D) to detect FMDV in
      clinical samples. There was concordance between the results generated by the 2
      assays for 88.1% (347 of 394) of RNA samples extracted from suspensions of
      epithelial tissue obtained from suspect FMD cases. The comparison between the 2
      tests highlighted 19 FMDV isolates (13 for the 5'UTR and 6 for the 3D assay),
      which failed to produce a signal in 1 assay but gave a positive signal in the
      other. The sequence of the genomic targets of selected isolates highlighted
      nucleotide substitutions in the primer or probe regions, thereby providing an
      explanation for negative results generated in the rRT-PCR assays. These data
      illustrate the importance of the continuous monitoring of circulating FMDV field
      strains to ensure the design of the rRT-PCR assay remains fit for purpose and
      suggest that the use of multiple diagnostic targets could further enhance the
      sensitivity of molecular methods for the detection of FMDV.

PMID- 16566265
TI  - Use of reverse transcription-polymerase chain reaction to determine the stability
      of rabies virus genome in brains kept at room temperature.
AB  - In tropical and subtropical climates, the shipment of animal brains for rabies
      diagnosis may be a problem because brain specimens sometimes arrive decomposed at
      the diagnostic laboratory. In this situation, reverse transcription-polymerase
      chain reaction (RT-PCR) may serve as a potential solution because of its high
      sensitivity. However, little is known about the stability of rabies viral RNA in
      decomposed brain tissue. To determine the stability of rabies virus genomic RNA
      in brain samples, 72 mice were inoculated with the challenge virus strain-11 of
      rabies virus. After incubation period, mice were euthanized to obtain their
      brains. These were categorized in 2 different groups. In the first group, 36
      brains were kept at room temperature (25-27 degrees C) immediately after
      euthanasia. In the second group, the other 36 inoculated brains were frozen at 
      70 degrees C and later maintained at room temperature. In both groups, RT-PCR was
      performed at days 0, 1, 2, 3, 4, 7, 10, 12, 16, 18, 23, and 26 by using primers
      previously described in the literature and a primer set specifically designed for
      a Mexican variant of vampire-bat rabies. Reverse-transcriptase PCR experiments
      were performed in 3 different inoculated brains, in which the direct fluorescent
      antibody (DFA) test was previously conducted to detect rabies viral antigen in
      the brains kept at room temperature and in the frozen brains. The DFA test
      resulted positive in both groups up to day 7. In brain samples stored at ambient
      temperature (25-27 degrees C), the intensity of the RT-PCR band started to
      diminish by day 12; however, rabies virus genome could be successfully amplified
      by RT-PCR up to 23 days. These results indicate that brain samples kept at
      ambient temperature (up to 27 degrees C) may reach a reference laboratory in an
      adequate state for rabies diagnosis by RT-PCR.

PMID- 16566266
TI  - Efficient screening of the cystinuria-related C663T Slc3a1 nonsense mutation in
      Newfoundland dogs by denaturing high-performance liquid chromatography.
AB  - Cystinuria in Newfoundland dogs is a metabolic disease associated with a nonsense
      mutation in the exon 2 of the Slc3a1 gene. Similar to type I human cystinuria,
      heterozygote carriers are not affected by the disease and do not reveal
      differences in urinary concentration of dibasic amino acids when compared with
      normal dogs. However, through a recessive mode of inheritance, these dogs are
      able to transmit the disease to their offspring. Early detection of mutation
      carriers through cost-effective reliable methods is therefore essential for the
      implementation of breeding methods aimed at the eradication of the disease.
      Denaturing high-performance liquid chromatography (DHPLC) is a recently developed
      technique for rapid and efficient screening of nucleotide polymorphisms in
      polymerase chain reaction-amplified products. This technique was used for the
      identification of the C663T Slc3a1 mutation in Portuguese Newfoundland dogs.
      Polymerase chain reaction products amplified from a region containing the C663T
      locus were subjected to DHPLC analysis, and results were double checked by DNA
      sequencing. Results showed the presence of the mutation in 6 of the 22 dogs
      tested. Urine biochemical parameters correlated well with the number of mutated
      Slc3a1 copies, and homozygotes for the C663T mutation were the only dogs
      diagnosed with cystinuria. Sequence analysis confirmed the DHPLC results,
      demonstrating that the technique could be a reliable alternative to sequencing
      for the rapid and cost-effective identification of mutations in canine breeds.

PMID- 16566267
TI  - Comparison of three monoclonal antibodies for use in immunohistochemical
      detection of bovine spongiform encephalopathy protease-resistant prion protein.
AB  - Confirmatory diagnosis of prion diseases in humans and animals relies on the
      histopathological examination and immunodetection of the protease-resistant
      isoform of prion protein (PrPres). The generation of novel PrP-specific
      monoclonal antibodies (MAbs) has greatly improved diagnostic methodology and
      basic research on prion diseases as well. In this study, the performance of 3
      different PrP-specific MAbs in recognizing brain PrPres deposits from cows
      affected with bovine spongiform encephalopathy (BSE) was compared by using a
      standard immunohistochemical technique under different pretreatment conditions.
      All antibodies showed similar reactivity after denaturing treatment. However,
      greater differences were found among them after proteinase K treatment, even in
      the absence of a denaturing step. In fact, 1 MAb (2A11) was able to react with
      PrPres deposits in the absence of a denaturing step, yielding the strongest
      signal and confirming the usefulness of MAb 2A11 in immunohistochemistry for the
      diagnosis of BSE.

PMID- 16566268
TI  - Preliminary observations of genetic susceptibility of elk (Cervus elaphus
      nelsoni) to chronic wasting disease by experimental oral inoculation.
AB  - To compare the genetic susceptibility of elk (Cervus elaphus nelsoni) with
      various alleles of the PRNP gene, which encodes the normal cellular prion
      protein, to chronic wasting disease (CWD), eight 8-month-old elk calves of 3
      genotypes (2 132MM, 2 132LM, and 4 132LL) were orally dosed with CWD-infected
      brain material from elk. During postinoculation (PI) month 23, both 132MM elk had
      lost appetite, developed clinical signs of weight loss and central nervous system
      (CNS) dysfunction, and were euthanized. Two other elk (both 132LM) developed
      similar clinical signs of disease and were euthanized during PI month 40. All 4
      affected elk had microscopic lesions of spongiform encephalopathy (SE), and
      PrPres, the disease-associated form of the prion protein, was detected in their
      CNS and lymphoid tissues by use of immunohistochemical (IHC) and Western blot
      (WB) techniques. These findings indicate that elk with MM and LM at codon 132 are
      susceptible to orally inoculated CWD. All 4 LL elk are alive at PI year 4 and are
      clinically normal, which suggests that 132LL elk may have reduced susceptibility
      to oral infection with CWD-infected material or may have prolonged incubation
      time.

PMID- 16566269
TI  - Histologic assessment and grading of the exocrine pancreas in the dog.
AB  - Histologic grading schemes for canine inflammatory conditions are sparse, and in
      the case of the canine pancreas, have not been previously described. In a
      previous study, we determined that histologic lesions of the exocrine pancreas
      occurred much more frequently than gross lesions. The intention of the current
      study was to develop a histologic grading scheme for nonneoplastic lesions
      following extensive assessment of the exocrine pancreas from dogs presented for
      necropsy examination. The parameters of the proposed scheme include neutrophilic
      inflammation, lymphocytic inflammation, pancreatic necrosis, pancreatic fat
      necrosis, edema, fibrosis, atrophy, and hyperplastic nodules. In this case
      series, the most common lesion was pancreatic hyperplastic nodules (80.2%),
      followed by lymphocytic inflammation (52.5%), fibrosis (49.5%), atrophy (46.5%),
      neutrophilic inflammation (31.7%), pancreatic fat necrosis (25.7%), pancreatic
      necrosis (16.8%), and edema (9.9%). Only 8 of the 101 animals had no evidence of
      any of the lesions in any of the sections examined. Fibrosis, atrophy, and/or
      lymphocytic infiltration most commonly accompanied nodules. Neutrophilic
      inflammation, when present, was often associated with necrosis (pancreatic
      necrosis, pancreatic fat necrosis, or both) and occasionally with hyperplastic
      nodules. The utilization of a grading scheme for exocrine pancreatic lesions will
      be useful in advancing the classification of exocrine pancreatic disease in the
      dog, which may lead to multicenter studies of exocrine pancreatic disorders in
      the dog and in other species.

PMID- 16566270
TI  - A devastating outbreak of malignant catarrhal fever in a bison feedlot.
AB  - In early 2003, an outbreak of malignant catarrhal fever (MCF) occurred in a bison
      feedlot in southern Idaho. The outbreak resulted in a 51.2% (n = 825) mortality
      rate among bison, which had been exposed to sheep for 19 days. Diagnosis was made
      by detection of ovine herpesvirus 2 (sheep-associated MCF virus) DNA in tissues
      or peripheral blood by polymerase chain reaction (PCR), and by histological
      examination of tissue lesions. Peak losses occurred between 41 and 55 days
      postmean exposure time (PME), and reached a maximum of 41 head per day. No known
      cases of MCF were observed among the 177 head of bison that arrived in the lot 3
      1/2 weeks after the departure of the sheep. Of the several thousand head of beef
      cattle in the lot during the outbreak, only a single case of MCF was identified.
      This outbreak illustrates the devastating impact the MCF virus can have on bison
      under certain exposure conditions, the high threat posed by adolescent lambs to
      susceptible species, the significantly greater susceptibility of bison than beef
      cattle to MCF, and the lack of horizontal transmission from clinically affected
      bison to herdmates.

PMID- 16566271
TI  - Survey of equine cutaneous neoplasia in the Pacific Northwest.
AB  - A retrospective study examined data regarding equine cutaneous and mucocutaneous
      neoplasms submitted to the Veterinary Diagnostic Laboratory at Oregon State
      University in a 3.5-year period. A total of 536 neoplasms were identified,
      accounting for 30% of the total equine pathology submissions. Sarcoid, squamous
      cell carcinoma, melanocytic tumors, papillomas, and mast cell tumors were the
      most common neoplasms, constituting 87.5% of all cutaneous neoplasms. Sarcoids
      represented 51.4% of all neoplasms and 15.18% of total equine accessions. Sarcoid
      was most common in paints, quarter horses, and Arabians, and was the only common
      tumor in donkeys and mules. Mean age at diagnosis of equine sarcoid was 9 years.
      Squamous cell carcinoma constituted 18.3% of all neoplasms and 5.41% of total
      equine accessions. Ocular squamous cell carcinoma was most common in paints and
      quarter horses, and penile/preputial squamous cell carcinoma was most common in
      appaloosas and quarter horses. The mean age of horses with ocular squamous cell
      carcinoma (13 years) and squamous cell carcinoma of the skin (15 years) was
      significantly less (P < 0.5) than that of horses with squamous cell carcinoma of
      the penis and prepuce (21 years) or vulva, anal, and perianal skin (19 years).
      Findings suggest that equine sarcoid and squamous cell carcinoma occur more
      frequently in the Pacific Northwest than in the northeastern United States.

PMID- 16566272
TI  - Compressive myelopathy due to intervertebral disk extrusion in a llama (Lama
      glama).
AB  - A 12-year-old intact female llama was euthanized following acute onset of spastic
      tetraparesis and recumbency with inability to rise. Postmortem examination
      revealed caudal cervical spinal cord compression due to a mass within the ventral
      spinal canal arising from the C6-C7 intervertebral disk space and attached to an
      irregularly thickened annulus fibrosis. On histopathologic examination, the mass
      was composed of amorphous acellular basophilic to amphophilic material admixed
      with irregularly arranged collagen bundles. The amorphous material was
      metachromatic and contained multiple small foci of markedly vacuolated round
      cells, characteristic of origin from the nucleus pulposus. Severe necrosis of all
      white matter tracts with astrocytic reaction was present in the overlying spinal
      cord segment. Ascending and descending Wallerian degeneration and dissecting
      interstitial astrogliosis were present within white matter tracts above and below
      the lesion, respectively. The diagnosis was compressive myelopathy due to chronic
      extrusion of the nucleus pulposus of the C6-C7 intervertebral disk. To the
      authors' knowledge, this is the first report of intervertebral disk disease in a
      camelid.

PMID- 16566273
TI  - Disseminated transmissible venereal tumor in a dog.
AB  - Transmissible venereal tumor (TVT) is a well-documented transplantable tumor in
      dogs, with no breed or sex predilection and a low metastatic rate. In this
      report, a 2-year-old intact female Mastiff that had numerous, rapidly growing
      masses throughout the subcutis mainly at the dorsal body plane, the caudal half
      of the ventral abdomen, and around the vulva was euthanized due to poor
      prognosis. Neoplastic nodules similar to those seen in the subcutis were also
      noted in the lung, anterior mediastinum, liver, spleen, kidney, and superficial
      and deep lymph nodes in both abdominal and thoracic cavities. The neoplastic
      nodules from the subcutis as well as metastatic foci revealed similar cytologic
      and histologic features, which were consistent with canine TVT. By
      immunohistochemical staining, the neoplastic cells were positive for lysozyme and
      vimentin but were negative for cytokeratin, desmin, CD3, and CD79a. The diagnosis
      of the TVT was further supported by the identification and analysis of long
      interspersed nuclear elements (LINE) from paraffin-embedded tumor tissue. This
      case is a rare example of TVT with multiorgan metastasis. In this case, the
      polymerase chain reaction technique was useful in differential diagnosis of
      canine round cell tumors because this technique can be applied in retrospective
      as well as future study.

PMID- 16566274
TI  - Thallium toxicosis in a Pit Bull Terrier.
AB  - Thallotoxicosis is described in an adult Pit Bull Terrier. The dog exhibited
      anorexia, emesis, weakness, conscious proprioceptive deficits, and a hemorrhagic
      diarrhea before death. A severe, acute necrotizing enterocolitis was evident upon
      histological examination, as was a multifocal to coalescing pulmonary edema.
      Liver and kidney thallium concentrations were 18 and 26 ppm, respectively. The
      source of the thallium was determined to be thallium sulfate obtained by a person
      with the intent to harm family members. Although thallium has not been produced
      in the United States for 20 years, this report demonstrates the need to consider
      thallium toxicosis as a differential diagnosis for animals presenting with vague
      and mixed gastrointestinal and neurological signs.

PMID- 16566275
TI  - Application of alpha-methylacyl coenzyme A racemase immunohistochemistry in the
      diagnosis of prostate cancer: a review.
AB  - Alpha-methylacyl coenzyme A racemase (AMACR) is a recently discovered enzyme
      protein that has been shown to be increased at both the mRNA and protein levels
      in prostatic adenocarcinoma as compared with normal prostatic tissues. Since its
      discovery, AMACR has gained wide acceptance for use in the diagnosis of prostatic
      adenocarcinoma in conjunction with morphology and immunohistochemical staining
      for basal cell markers. Numerous studies have consistently shown high sensitivity
      and specificity of AMACR for prostate cancer. This review focuses on AMACR
      expression in prostate cancer and its morphologic variants, high grade prostatic
      intraepithelial neoplasia, adenosis and benign conditions of the prostate. In
      addition, we discuss AMACR expression in other tumors. We also focus on the
      utility and technical aspects of the now-popular "triple stain"
      immunohistochemical antibody cocktail, consisting of antibodies to high-molecular
      weight keratin, p63 and AMACR. Finally, we emphasize diagnostic pitfalls in the
      application of AMACR to small, atypical foci of glands seen on prostate needle
      core biopsy and project future diagnostic as well as clinical applications for
      the protein.

PMID- 16566276
TI  - Analysis of CD36 expression on human monocytic cells and atherosclerotic tissue
      sections with quantum dots: investigation by flow cytometry and spectral imaging
      microscopy.
AB  - OBJECTIVE: To demonstrate CD36 expression with quantum dots (QDs) 525 and/or 605
      on human monocytic U937 cells and atherosclerotic tissue sections by means of
      flow cytometry (FCM) and/or confocal laser scanning microscopy (CLSM). STUDY
      DESIGN: U937 cells and tissue sections were analyzed by means of FCM and/or CLSM.
      FCM was performed, using different ultraviolet (UV) and visible (488/532 nm)
      excitation modes. In the visible mode, fluorescence intensities of QDs,
      phycoerythrin (PE) and fluorescein isothiocyanate (FITC) were compared. Three
      dimensional (3-D) sequences of images were obtained by spectral analysis in a
      CLSM and analyzed by the factor analysis of medical image sequences (FAMIS)
      algorithm, providing factor curves and images. Factor images are the result of
      the FAMIS image processing method, which differentiates emission spectra from 3D
      sequences of images. In CLSM analysis, preparations are screened in a UV
      excitation mode to optimize the possibilities of QDs and have the benefit of 4',6
      diamino-2-phenylindole or Hoechst 33342 counterstaining of nuclei. RESULTS: FCM
      and CLSM revealed CD36 expression by means of QDs 525 and/or 605. Fluorescence
      intensity of PE and of FITC was higher than that of QDs 525 and of 605. As factor
      curves and images show the red emission of QDs 605 only, subsequent reliable
      identification and localization of CD36 was obtained. CONCLUSION: QDs 525 and 605
      are useful to analyze antigenic expression. Following FCM, which is well adapted
      to detect fluorescence emission of QDs in the UV or visible excitation mode, CLSM
      and subsequent spectral analysis assess more specific characterization of QD
      fluorescent emissions.

PMID- 16566277
TI  - Theory and implementation of an electronic, automated measurement system for
      images obtained from immunohistochemically stained slides.
AB  - OBJECTIVE: To develop and implement an Internet-based, automated image
      measurement system for immunohistochemically stained slides including
      fluorescence images in online and off-line modes. STUDY DESIGN: An image
      analyzing system was developed that automatically measures digitized images
      obtained from immunohistochemically stained slides. It is divided into a common
      server platform and a specific image quantification system based upon DIAS
      (University of Jena). After registration, the user fills in an input data form
      and attaches images to be measured. The server periodically transfers the data to
      the measurement system. The measurement works on dynamic thresholding and active
      sampling of objects visualized by fluorescence and conventional chromogens. It
      includes stereologic algorithms, object quantification, syntactic structure
      analysis and quality assurance. RESULTS: The system has been tested for
      diaminobenzidene, alkaline phosphatase and fluorescence images (FITC, etc.). The
      reproducibility and stability of the system are > 98%. The series of successfully
      measured images comprises > 1,000 images in total in the online and off-line
      modes. CONCLUSION: An Internet-based automated image measurement system has been
      developed that offers worldwide access to the major requests for quantification
      of immunohistochemically stained slides-tissue array analysis, nuclear stains
      (MIB, hormones), membrane stains (CerbB2), vascularization and fluorescence in
      situ hybridization.

PMID- 16566278
TI  - Malignant fibrous histiocytoma of the glans penis: a case report.
AB  - BACKGROUND: Malignant fibrous histiocytoma has been regarded as the most common
      sarcoma of older adults. However, recent opinion regards pleomorphic malignant
      fibrous histiocytoma as an undifferentiated high grade pleomorphic sarcoma not
      otherwise classifiable utilizing current techniques available in surgical
      pathology. Notwithstanding controversy regarding its nomenclature, malignant
      fibrous histiocytoma involving the penis is exceedingly rare, with only 4 cases
      previously described, to our knowledge. CASE: An uncircumcised 73-year-old male
      presented with a painless, granular, partially necrotic lesion beneath the penile
      foreskin. There was no history of sexually transmitted disease, constitutional
      symptoms or dysuria. Examination of penile shaft, testicles, spermatic cord and
      inguinal lymph nodes were unremarkable. Biopsy revealed a markedly pleomorphic
      sarcoma. Subsequent, partial penectomy revealed the same lesion with an adjacent
      area of squamous cell carcinoma in situ. CONCLUSION: Malignant fibrous
      histiocytoma remains a diagnosis of exclusion. The investigation requires
      extensive tumor sampling in search of areas of differentiation and a complete
      battery of immunohistochemical markers. Therapeutically important entities in the
      differential diagnosis that must be ruled out include other poorly differentiated
      sarcomas, sarcomatoid squamous cell carcinoma and desmoplastic melanoma.

PMID- 16566279
TI  - Application of Photoshop and Scion Image analysis to quantification of signals in
      histochemistry, immunocytochemistry and hybridocytochemistry.
AB  - OBJECTIVE: To describe a simple method to achieve the differential selection and
      subsequent quantification of the strength signal using only one section. STUDY
      DESIGN: Several methods for performing quantitative histochemistry,
      immunocytochemistry or hybridocytochemistry, without use of specific commercial
      image analysis systems, rely on pixel-counting algorithms, which do not provide
      information on the amount of chromogen present in the section. Other techniques
      use complex algorithms to calculate the cumulative signal strength using two
      consecutive sections. To separate the chromogen signal we used the "Color range"
      option of the Adobe Photoshop program, which provides a specific file for a
      particular chromogen selection that could be applied on similar sections. The
      measurement of the chromogen signal strength of the specific staining is achieved
      with the Scion Image software program. CONCLUSION: The method described in this
      paper can also be applied to simultaneous detection of different signals on the
      same section or different parameters (area of particles, number of particles,
      etc.) when the "Analyze particles" tool of the Scion program is used.

PMID- 16566280
TI  - A stereologic approach to estimate the number of immunogold-labeled molecules in
      cells of tubules.
AB  - OBJECTIVE: The quantity of molecules can be measured very precisely by molecular
      biological methods, but the capabilities of these are limited to measure only the
      total mass of tissue. For estimating the number of molecules at the cell level,
      it is necessary to combine an immunohistochemical protocol with designed-based
      principles of stereology at the level of electron microscopy (EM). This article
      focuses on the problems and practical solutions of fitting together
      immunohistochemistry, stereology, and electron microscopy for the estimation of
      the number of angiotensin II AT1 receptors in rat kidney arterioles. STUDY
      DESIGN: We performed the preembedding immunostaining of angiotensin II AT1
      receptors using the silver-enhanced immunogold labeling system at EM level on
      serial sections of renal arterioles from 5 rats. RESULTS: Using this method the
      number of molecules can be estimated along the renal arterioles separately on the
      cell's surface, in cytoplasm, in nucleus, or in any subcellular location.
      CONCLUSION: For estimating the number of AT1 receptors, we designed a protocol
      that took into account the requirements for both immuno-EM and stereology. This
      method can be applied for estimating any molecule number in different types of
      cells in tubules.

PMID- 16566281
TI  - The evolution of azelaic acid.
AB  - Azelaic acid (AzA) is a naturally occurring dicarboxylic acid that has a long and
      complex history in the treatment of skin disorders. We summarize research on AzA
      from the past 25 years and follow its progress from a treatment of
      hyperpigmentation to a therapy for acne vulgaris and inflammatory
      (papulopustular) rosacea.

PMID- 16566282
TI  - The rationale for advancing the formulation of azelaic acid vehicles.
AB  - When first approved in December 2002, 15% azelaic acid (AzA) gel represented a
      significant advance over the available 20% AzA cream. Although a smaller amount
      of AzA was present in the new formulation, the gel medium provided a highly
      effective system for delivering the active ingredient, thus providing more
      effective treatment. This article explores the nature of these 2 vehicles and
      highlights the importance of the formulation in which dermatologic drugs are
      delivered.

PMID- 16566283
TI  - A clinical overview of azelaic acid.
AB  - Azelaic acid (AzA) initially was released in a 20% cream formulation, which has
      been shown to be effective in the treatment of mild to moderate rosacea.
      Recently, a 15% gel formulation was developed that vastly improved the delivery
      of AzA and has been proven by multiple studies to be effective in the treatment
      of rosacea. We present studies that examine both of these formulations, first in
      comparison with their vehicles and then in contrast with other well-accepted
      topical treatments of rosacea, such as metronidazole cream and gel.

PMID- 16566284
TI  - Case studies.

PMID- 16566285
TI  - The use of topical azelaic acid for common skin disorders other than inflammatory
      rosacea.
AB  - Topical azelaic acid (AzA) is approved for the treatment of acne vulgaris and
      inflammatory (papulopustular) rosacea. Because of diverse mechanisms of action
      that correlate with potential therapeutic benefit, AzA has been used to treat
      several common dermatoses including acne vulgaris, inflammatory rosacea,
      erythematotelangiectatic rosacea, perioral dermatitis, melasma, and
      postinflammatory hyperpigmentation. This article reviews the therapeutic use of
      topical AzA for the treatment of common skin disorders other than the US Food and
      Drug Administration (FDA)-approved indications of acne vulgaris and inflammatory
      rosacea.

PMID- 16566286
TI  - Viral and non-viral methods for gene transfer into skeletal muscle.
AB  - Skeletal muscle is an important target for genetic manipulation and its stable
      post-mitotic nature allows the use of both integrating and non-integrating viral
      and non-viral vectors. Adeno-associated viral vectors and naked plasmid DNA are
      currently the vectors of choice for gene transfer into muscle. The last couple of
      years have seen major breakthroughs in the field of vector delivery systems,
      particularly those using the vascular route, such that gene therapy of muscular
      dystrophies and the use of muscle as a platform for the production of secreted
      proteins has become a clinical possibility.

PMID- 16566287
TI  - Embryonic stem cells: a great hope for a new era of medicine.
AB  - Current stem-cell research has the potential to lead to new approaches for the
      treatment of cardiovascular, neurodegenerative and musculoskeletal diseases, as
      well as diabetes and cancer. Stem-cell-based approaches could be employed in cell
      replacement therapy or in drug treatments that encourage adult stem cells to
      migrate and activate at a site of injury or disease. For such therapeutic
      approaches to be successful, a greater understanding of the signaling pathways
      that determine the diverse developmental fates of these cells is needed. From a
      drug-discovery perspective, efforts are being deployed in developing cell-based
      assays to screen for small molecules that can modulate stem-cell fate. Such
      compounds will provide new insights into stem-cell biology, and may ultimately
      contribute to effective disease treatments.

PMID- 16566288
TI  - In search of p53 target genes for the therapeutic manipulation of cancer.
AB  - As a tumor suppressor protein, p53 plays a crucial role in cancer development.
      Direct associations between p53, apoptosis and drug response suggest that
      targeting genes/gene products downstream of p53 may have clinical benefits. The
      completion of the human genome project and the availability of microarray
      technology have led to new ways in which to define the global regulatory network
      of p53 and to search for oncogenes in the p53 pathway. A crucial step toward
      antitumor drug discovery is the mapping of p53 transcriptomes onto cancer
      phenomes. In this review, recent developments in the genome-wide search of p53
      target genes are discussed, along with current efforts in high-throughput
      antitumor target discovery in the p53 pathway and recent progress in the
      pharmacological modulation of targets downstream of p53 for effective cancer
      therapy.

PMID- 16566289
TI  - Bispecific antibodies for dual-modality cancer therapy: killing two signaling
      cascades with one stone.
AB  - The additive and synergistic therapeutic effects derived from combinations of
      chemotherapeutic drugs and radiation have established an indispensable paradigm:
      cancer must be attacked on multiple fronts. However, the increased antitumor
      efficacy of such combinational regimens is also associated with severe systemic
      toxicity, as these drugs cannot selectively target tumor cells. Monoclonal
      antibodies (mAbs), which have exquisite specificity for their antigens, are
      becoming an increasingly important class of antitumor agents, as they enhance the
      efficacy of various therapeutic regimens without significantly increasing
      systemic toxicity. Furthermore, preclinical and early clinical evidence indicate
      that combinations of antibody-based drugs provide even greater efficacy with
      minimal side effects. Unfortunately, the research, manufacturing and regulatory
      costs of mAb development pose a significant barrier to the use of antibody-based
      combination therapies. An emerging alternative is the use of dual-targeting
      bispecific antibodies (BsAbs). BsAbs are derived from the recombination of
      variable domains of two antibodies with different specificities; BsAbs are thus
      capable of binding both antigens of their parental antibodies. With the recent
      progress that has been made in antibody engineering technology, BsAbs that
      simultaneously target two tumor-associated molecules (eg, growth factor
      receptors) are being heralded for their potential to deliver two therapeutic
      moieties in a single molecule.

PMID- 16566290
TI  - Toward oligosaccharide- and glycopeptide-based HIV vaccines.
AB  - The human immunodeficiency virus (HIV) is the causative agent of acquired immune
      deficiency syndrome (AIDS), and HIV type 1 (HIV-1) is responsible for the current
      global pandemic of HIV and AIDS. There is widespread agreement that the best hope
      to contain this pandemic is the development of an effective HIV-1 vaccine. The
      major difficulty in HIV vaccine design, however, is in identifying novel epitopes
      for inducing broadly neutralizing antibodies. Accumulating data have implied that
      the HIV-1 carbohydrates, which are a strong defense against host immune attack,
      can also serve as targets for vaccines. This notion was reinforced by the
      characterization of a novel oligomannose cluster on HIV-1 glycoprotein gp120 as
      the epitope of the broadly neutralizing antibody 2G12. This review describes the
      current status and prospective of the progress toward a carbohydrate-based HIV
      vaccine. Recent research on the design, synthesis and antigenicity of HIV-1
      oligosaccharides and glycopeptide immunogens is also discussed.

PMID- 16566291
TI  - Mouse models of inflammatory bowel disease.
AB  - The past decade has seen an abundance of new mouse models that mimic the human
      inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis. These
      mouse models of IBD have provided great insight into the potential mechanisms
      that drive homeostatic dysregulation in the intestine, which manifests as mucosal
      inflammation. Within this review, the different animal models that have been
      employed to gain a greater understanding of the pathogenesis of IBD are discussed
      and some of the new biological drugs that have emerged as potential therapeutics
      as a result of these mouse modeling studies are reviewed.

PMID- 16566292
TI  - Cellular pharmacodynamics and pharmacokinetics of antibiotics: current views and
      perspectives.
AB  - The treatment of intracellular infections requires the use of antibiotics
      presenting appropriate cellular pharmacokinetic and pharmacodynamic properties.
      These properties, however, cannot be predicted on the simple basis of cellular
      drug accumulation and minimum inhibitory concentration in broth. In most cases,
      intracellular activity is actually lower than extracellular activity, despite the
      fact that all antibiotics reach intracellular concentrations that are at least
      equal to, and more often higher than the extracellular concentrations. This
      discrepancy may result from impairment of the expression of antibiotic activity
      or a change in bacterial responsiveness inside the cells. It therefore appears
      important to evaluate the intracellular activity of antibiotics in appropriate
      models.

PMID- 16566293
TI  - From genome to phenome--RNAi library screening and hit characterization using
      signaling pathway analysis.
AB  - Comprehensive, high-throughput analysis of gene function using RNA interference
      (RNAi)-based screens is emerging as a significant step forward for preliminary
      drug-target identification. Until quite recently drug target identification
      depended heavily on the analysis of changes in gene expression, which in turn
      needed to be correlated with gene function. The promise of obtaining preliminary
      'gene to phenotype' information using a single high-throughput platform is
      propelling major investment in this area by biotechnology and pharmaceutical
      companies. This review discusses recent developments in the use of RNAi library
      screens, and the various assay formats and techniques currently in use for data
      analysis downstream of such screens.

PMID- 16566294
TI  - Advances in systems biology: measurement, modeling and representation.
AB  - Systems biology is frequently defined as the study of all of the elements in a
      biological system and their relationship to one another in response to
      perturbation. Advances in science and technology are enabling the development of
      this emerging and cross-disciplinary field by allowing researchers to explore how
      biological components function as a network in cells, tissues and organisms.
      Recently, pharmaceutical companies have begun to embrace systems approaches in an
      effort to better understand physiology, pathogenic processes and pharmacological
      responses. This review focuses on recent advances within three core areas of
      systems biology: data collection, data analysis, and the integration and sharing
      of data.

PMID- 16566295
TI  - The cyclotides and related macrocyclic peptides as scaffolds in drug design.
AB  - The applicability of linear peptides as drugs is potentially limited by their
      susceptibility to proteolytic cleavage and poor bioavailability. Cyclotides are
      macrocyclic cystine-knotted mini-proteins that have a broad range of
      bioactivities and are exceptionally stable, being resistant to chemical, thermal
      and enzymatic degradation. The general limitations of peptides as drugs can
      potentially be overcome by using the cyclotide framework as a scaffold onto which
      new activities may be engineered. The potential use of cyclotides and related
      peptide scaffolds for drug design is evaluated herein, with reference to
      increasing knowledge of the structures and sequence diversity of natural
      cyclotides and the emergence of new approaches in protein engineering.

PMID- 16566296
TI  - Engineered protein inhibitors of proteases.
AB  - The control of proteolysis in an organism is achieved under normal circumstances
      through a balance of protease production, degradation and inactivation, via
      interaction with an endogenous inhibitor. When one of these mechanisms for
      control of proteolysis fails, it can result in the onset or progression of
      disease. Control of aberrant proteolysis is, therefore, a potetntial point of
      therapeutic intervention, and can be achieved either through the replacement of
      an absent endogenous inhibitor or by dosing with an inhibitor that is specific
      for a protease that is being over produced. Engineered protein inhibitors of
      proteases offer the potential to overcome the difficulties involved in
      identifying specific inhibitors via small-molecule-based approaches.

PMID- 16566297
TI  - Exploiting directed evolution for the discovery of biologicals.
AB  - Protein-based drugs offer unique advantages over small-molecule drugs in terms of
      both discovery and therapeutic use. The advent of recombinant DNA technology
      enabled the production of recombinant proteins and the generation of partially or
      fully human monoclonal antibodies, and continued developments in molecular
      biology have provided powerful approaches to generate improved proteins with more
      drug-like features. In this review, the benefits of using an evolutionary
      approach to biologicals drug discovery are discussed, with emphasis on the use of
      in vitro evolution technologies, such as ribosome display.

PMID- 16566299
TI  - Evidence-based medicine.

PMID- 16566298
TI  - South Dakota legislative report.

PMID- 16566300
TI  - Tele-echocardiography in neonates: utility and benefits in South Dakota primary
      care hospitals.
AB  - BACKGROUND: Live transmission of echocardiography can provide a rapid and
      accurate diagnosis in identifying neonates who need emergent transfer to a
      tertiary care center. This prevents a delay in management and/or unnecessary
      transport. OBJECTIVE: The purpose of this study was to review the utility,
      accuracy, and benefits of tele-echocardiography in primary care hospitals in
      South Dakota to assess neonates with suspected congenital heart disease. METHOD:
      Two primary care hospitals established a telemedicine link to our tertiary care
      center. A pediatric cardiologist interpreted neonatal tele-echocardiograms and
      results with recommendations were immediately communicated to the attending
      physicians. RESULTS: Seventy-six neonatal studies were performed over 30 months,
      72 at the primary care sites and 4 at the tertiary care center. Cardiac diagnosis
      was identified in 30 patients (40%). Neonatal transport was deemed necessary in 8
      patients (11%), 5 with major cardiovascular disease and 3 with persistent
      pulmonary hypertension of the newborn. Two pre-term infants at the tertiary
      center were diagnosed with patent ductus arteriosus and required medical
      intervention. CONCLUSION: Tele-echocardiography accurately distinguished neonates
      who required tertiary cardiac care from those with less critical cardiac disease
      fostering prompt diagnosis and appropriate care while subjecting a minimal number
      of patients to costly emergency transport.

PMID- 16566301
TI  - Choanal atresia: endoscopic repair in three recent cases and a review of the
      literature.

PMID- 16566302
TI  - Spinal stenosis.
AB  - Spinal stenosis can be generally described as the narrowing of the spinal canal
      causing compression of the spinal cord. This compression most often occurs in the
      lumbar portion of the spine and has a clinical presentation of pain and numbness
      in the low back, legs and buttocks after walking or extension of the lumbar
      spine. The symptoms associated with lumbar spinal stenosis are usually relieved
      with flexion of the lower back. In addition, compression at the cervical spine
      has occasionally been seen in combination with lumbar spinal stenosis, with
      thoracic spinal stenosis occurring only rarely. Therefore, because spinal
      stenosis is the most prevalent preoperative diagnosis for spine surgery and
      affects nearly 5 of every 1000 Americans older than 50 years old, it is
      imperative to understand the role of spinal stenosis in generating back and leg
      pain. In this article an overview of the etiology, treatment, and outcomes will
      be presented to give a better understanding of this condition.

PMID- 16566303
TI  - Cultural competence in health care: what is it?

PMID- 16566304
TI  - Cancer reporting in South Dakota: an update.

PMID- 16566305
TI  - South Dakota risk pool.

PMID- 16566306
TI  - A doctor's story.

PMID- 16566307
TI  - Extenuating circumstances: Rasz and me.

PMID- 16566308
TI  - Tackling violence head on.

PMID- 16566309
TI  - Preparing for disaster.

PMID- 16566310
TI  - Wales: emergency care still in crisis.

PMID- 16566311
TI  - All in a day's work.

PMID- 16566312
TI  - Stating the facts.

PMID- 16566313
TI  - Blood transfusion in A&E.

PMID- 16566314
TI  - Practice makes perfect. An unusual knee injury.

PMID- 16566315
TI  - Developing the A&E nurse practitioner role.

PMID- 16566316
TI  - Nurses' knowledge of commonly used drugs: a clinical audit.

PMID- 16566317
TI  - Board's eye view.

PMID- 16566318
TI  - The use of nouns and verbs by Japanese children and their caregivers in book
      reading and toy-playing contexts.
AB  - Japanese provides a valuable contrast for crosslinguistic studies of noun and
      verb dominance in early child language, and the effect of input on the early
      lexicon. In this study, 31 Japanese children between 1;0 and 2;0 and their
      caregivers were recorded in two contexts: joint bookreading and play with toys.
      Context had the largest effect, as nouns were much more frequent in the book
      context. Noun dominance was constant across development in the book context, but
      in the toy context there was a shift away as children developed from single words
      through the presyntactic stage to the syntactic stage. Caregiver language was
      verb dominant in a number of respects across development in the toy context, and
      thus was not closely related to child lexical balance. We conclude that in early
      lexical development, all children have a conceptual disposition to learn nouns.
      With vocabulary growth and the emergence of grammar, the proportion of verbs
      increases substantially, and at this stage properties of the input language may
      influence development.

PMID- 16566319
TI  - Patterns of intra-word phonological variability during the second year of life.
AB  - Phonological representation for adult speakers is generally assumed to include
      sub-lexical information at the level of the phoneme. Some have suggested,
      however, that young children operate with more holistic lexical representations.
      If young children use whole-word representation and adults employ phonemic
      representation, then a component of phonological development includes a
      transition from holistic to segmental storage of phonological information. The
      present study addresses the nature of this transition by investigating the
      prevalence and patterns of intra-word production variability during the first
      year of lexical acquisition (1;0-2;0). Longitudinal data from four typically
      developing children were analysed to determine variability at each age. Patterns
      of variability are discussed in relation to chronological age and productive
      vocabulary size. Results show high overall rates of variability, as well as a
      peak in variability corresponding to the onset of combinatorial speech,
      suggesting that phonological reorganization may commence somewhat later than
      previously thought.

PMID- 16566320
TI  - Facilitating the acquisition of UNDER by means of IN and ON--a training study in
      Polish.
AB  - Forty Polish children aged between 1;8 and 2;3 were trained over two training
      sessions in the comprehension of the preposition POD [UNDER]. In the experiment,
      two variables were manipulated: a within subjects variable of SITUATION and a
      between subjects variable of LINGUISTIC INPUT. The effect of situation could be
      found in all trained groups, showing that children's understanding in familiar
      and transfer situations differed significantly from the performance of the
      control group in the post-test. The results further suggest that depending on the
      type of a situation, the linguistic task requires different word learning
      abilities from a child.

PMID- 16566321
TI  - 'To define means to say what you know about things': the development of
      definitional skills as metalinguistic acquisition.
AB  - Some authors have suggested that definitional skills include metalinguistic
      components (Watson, 1985; Snow, 1990; McGhee-Bidlack, 1991). The present study
      therefore empirically investigated relations between the ability to define words
      and level of metalinguistic awareness in 280 Italian children (with ages ranging
      from 5 to 11 years) and in two groups of 40 adults each (with low and high
      educational levels, respectively). We used a definitional task presenting 24
      terms (nouns, verbs, and adjectives, which were either concrete or abstract) and
      a task examining 6 different aspects of metalinguistic awareness. Our aim was to
      demonstrate that metalinguistic skills can positively predict the formal quality
      of definitions and to identify various aspects of metalinguistic skills that
      might be directly related to definitional skills. Results showed better
      performance on both tasks as a function of age and educational level; they also
      confirmed the important roles of metalinguistic ability and educational level in
      producing well-structured formal definitions.

PMID- 16566322
TI  - Perspective-shifts in event descriptions in Tamil child language.
AB  - Children are able to take multiple perspectives in talking about entities and
      events. But the nature of children's sensitivities to the complex patterns of
      perspective-taking in adult language is unknown. We examine perspective-taking in
      four- and six-year-old Tamil-speaking children describing placement events, as
      reflected in the use of a general placement verb (veyyii 'put') versus two fine
      grained caused posture expressions specifying orientation, either vertical (nikka
      veyyii 'make stand') or horizontal (paDka veyyii 'make lie'). We also explore
      whether animacy systematically promotes shifts to a fine-grained perspective. The
      results show that four- and six-year-olds switch perspectives as flexibly and
      systematically as adults do. Animacy influences shifts to a fine-grained
      perspective similarly across age groups. However, unexpectedly, six-year-olds
      also display greater overall sensitivity to orientation, preferring the vertical
      over the horizontal caused posture expression. Despite early flexibility, the
      factors governing the patterns of perspective-taking on events are undergoing
      change even in later childhood, reminiscent of U-shaped semantic reorganizations
      observed in children's lexical knowledge. The present study points to the
      intriguing possibility that mechanisms that operate at the level of semantics
      could also influence subtle patterns of lexical choice and perspective-shifts.

PMID- 16566323
TI  - Language in boys with fragile X syndrome.
AB  - The current paper reports of language production in 15 Hebrew-speaking boys, aged
      9;0-13;0, with fully methylated, non-mosaic fragile X syndrome and no concomitant
      diagnosis of autism. Contrary to expectations, seven children were non-verbal.
      Language production in the verbal children was studied in free conversations and
      in context-bound speech. Despite extra caution in calculating MLU, participants'
      language level was not predicted by mean utterance length. Context bound speech
      resulted in grammatically more advanced performance than free conversation, and
      performance in both contexts differed in important ways from performance of
      typically developing MLU-matched controls. The relevance of MLU as a predictor of
      productive grammar in disordered populations is briefly discussed.

PMID- 16566324
TI  - Word learning deficit among Chinese dyslexic children.
AB  - The present study examined word learning difficulties in Chinese dyslexic
      children, readers of a nonalphabetic script. A total of 105 Hong Kong Chinese
      children were recruited and divided into three groups: Dyslexic (mean age 8;8),
      CA control (mean age 8;9), and RL control (mean age 6; 11). They were given a
      word learning task and a familiar word writing task. It was found that the
      Dyslexic group performed less well than the RL group in learning irregular words
      over trials but not the regular ones. Error analyses showed that the Dyslexic
      group made more orthographic and word association errors but less intra-wordlist
      interference errors than the RL control group. The Dyslexic group also performed
      significantly less well than both control groups in writing familiar words (e.g.
      their own name). These findings suggest that Chinese dyslexic children have
      difficulty learning new words, especially irregular ones, and retaining
      overlearned words in long-term memory. We conclude that Chinese dyslexic children
      have a specific impairment in word learning like their alphabetic counterparts.

PMID- 16566325
TI  - Prelinguistic pitch patterns expressing 'communication' and 'apprehension'.
AB  - This study examined whether pitch patterns of prelinguistic vocalizations could
      discriminate between social vocalizations, uttered apparently with the intention
      to communicate, and 'private' speech, related to solitary activities as an
      expression of 'thinking'. Four healthy ten month old English-speaking infants (2
      boys and 2 girls) were simultaneously video- and audiorecorded in their homes
      under two conditions: (A) when the infant was playing with mother, and (B) when
      the infant was alone. One hundred and fifty-six vocalizations were classified as
      'communicative', if accompanied by non-vocal communicative behaviour, or as
      'investigative', if accompanied by explorative activities. For the acoustic
      analysis, an automatic PITCH PATTERN RECOGNITION (PPR) software system was
      developed. The PPR-system could distinguish 'communicative' from 'investigative'
      vocalizations with an overall accuracy of 91.67%. These findings confirm that
      prelinguistic vocalizations might serve both as means of purposeful communication
      and as a tool of thought. These are the functions later assumed by language.

PMID- 16566326
TI  - The Phonological Mean Length of Utterance: methodological challenges from a
      crosslinguistic perspective.
AB  - The present study assesses the phonological development of 17 children acquiring
      Finnish at the developmental point of 25 words (ages 1; 2-2;0). The analysis is
      made using the PHONOLOGICAL MEAN LENGTH OF UTTERANCE (PMLU) method (Ingram &
      Ingram, 2001; Ingram, 2002), which focuses on the children's whole-word
      productions. Two separate analyses are carried out: the first analysis
      concentrates on consonants and follows the procedure devised by Ingram and Ingram
      (2001), and the second analysis also scores the correctness of vowels. The PMLU
      results of both analyses are found to be much higher than those reported for
      children acquiring English. The results show the apparent need for more language
      specific research in order to develop the PMLU method suitable for various
      language environments.

PMID- 16566327
TI  - Note of clarification on the coding of light verbs in 'Semantic generality, input
      frequency and the acquisition of syntax' (Journal of Child Language 31, 61-99).

PMID- 16566328
TI  - Early relations between lexical and grammatical development in very immature
      Italian preterms.
AB  - This study aimed to investigate early lexical and grammatical development and
      their relations in a sample of very immature healthy preterms, in order to assess
      whether their linguistic development was typical, at risk or atypical. The
      effects of biological factors and parental level of education on preterms'
      linguistic development were also investigated. Seventy-three Italian preterms and
      22 Italian fullterms (control sample) were assessed at 2;6 with an Italian test
      of repetition of sentences (TRF). Their mothers completed the Italian version of
      the MacArthur questionnaire (PVB). Our results showed that most of the preterm
      sample displayed a typical development, compared with the fullterms, with lexicon
      and grammar within the normal range and a normal relation between these
      competencies. However, preterms characterized by an extremely low birthweight
      (ELBW), a very low gestational age and male gender were at risk, with slight
      delays in the lexicon and grammar, but still retaining the normal relation
      between the two.

PMID- 16566330
TI  - The march of the mentors.

PMID- 16566331
TI  - Edging towards a brave new IT world.

PMID- 16566332
TI  - A quick fix?
AB  - Recommendations from the National Institute for Health and Clinical Excellence
      say more people with high cholesterol levels should be prescribed statins. But
      some professionals have reservations. Currently 2 million people in England and
      Wales take statins. This figure will rise to 3.3 million with the change in
      threshold for statin treatment. The threshold for considering statin use has
      changed from a 30 per cent ten-year risk of developing cardiovascular disease to
      a 20 per cent or more risk. Statins in low dosage are available over the counter.

PMID- 16566333
TI  - On the right track. Interview by Lynne Wallis.
AB  - With experience in A&E and HIV awareness as well as charity work overseas, Derek
      Reale was looking for a change. Working for the British Transport Police, he is
      able to bring his nursing and counselling skills to the role of welfare officer.
      His role can include help with housing, debt counselling and relationship work.
      He can act as a point of referral for officers who would benefit from
      counselling. Organisational and practical support are part of his work.

PMID- 16566334
TI  - A sight to behold. Interview by Lynne Pearce.
AB  - Nurses in Bolton have improved bereavement care and increased the number of
      corneas donated for transplant. Through their educational efforts, hospital and
      community staff now feel more confident in broaching the subject with relatives.
      More than 2,500 staff have received training on multidisciplinary study days.
      Since the team have been in post the number of corneas for donation has increased
      by 335 per cent.

PMID- 16566335
TI  - Giving something back.

PMID- 16566336
TI  - Holistic listening.

PMID- 16566337
TI  - Prejudice undermines health promotion.

PMID- 16566338
TI  - Quality assurance and UK nurse education.
AB  - AIM: To evaluate the quality assurance model for nursing education in the United
      Kingdom (UK) for the first nine months after the inception in 2002 of the Nursing
      and Midwifery Council (NMC). METHOD: A specially designed questionnaire was
      administered to representatives of higher education institutions where nurse
      education took place and representatives of the NMC in all four countries of the
      UK. RESULTS: Quality assurance activity had taken place across the UK, mostly in
      the shape of validation events. Quality assurance events proceeded largely as
      expected by higher education and NMC representatives. There was a statistically
      significant trend towards greater preparedness and knowledge for validation and
      satisfaction with the new quality assurance procedures in Scotland, Wales and
      Northern Ireland compared with England. CONCLUSION: At the time of this study the
      new quality assurance procedures were less than 12 months old and there may have
      been resistance to change in England where the changes were greatest.

PMID- 16566339
TI  - Physiological observation track and trigger system.
AB  - A patient observation chart was developed to combine physiological observation
      charting with the calculation and recording of an early warning score (EWS); this
      was named the Physiological Observation Track and Trigger System (POTTS).
      Reference to a table of instructions is no longer needed and the EWS can be
      calculated with minimal error. Increased frequency and accuracy of EWS recording
      assist in identifying patients at risk of deterioration and enhance patient
      safety.

PMID- 16566340
TI  - Complications associated with venous access devices: Part two.
AB  - In the second of two articles the author discusses the secondary complications
      that can arise following insertion of venous access devices (VADs). Part one,
      published last week, examined the primary complications that can arise when
      inserting VADs.

PMID- 16566342
TI  - Lessons learned.

PMID- 16566341
TI  - Intestinal obstruction.

PMID- 16566343
TI  - Ambition and drive.

PMID- 16566344
TI  - Healthy futures.

PMID- 16566345
TI  - [Personal assistance--individually assigned nurses].

PMID- 16566346
TI  - [The encumbered world of nursing].

PMID- 16566347
TI  - [The family as a new focus of nursing?. Interview by Angelika Burkhard].

PMID- 16566348
TI  - [Deeply grasped changes].

PMID- 16566349
TI  - [Therapeutic touch of well-being].

PMID- 16566350
TI  - [Hypovolemic shock and what nurses can do].

PMID- 16566351
TI  - [Revolution instead of collapse in nursing].

PMID- 16566352
TI  - [Passive smoking is dangerous].

PMID- 16566353
TI  - [An evening in Parliament].

PMID- 16566354
TI  - [The laws concerning quality of life can really be carried out].

PMID- 16566356
TI  - [Misunderstanding in geriatric nursing. Discussion of the article "Renounced and
      abandoned" from PFLEGE AKTUELL 10/2005].

PMID- 16566355
TI  - [Who counts the introductory discussion?].

PMID- 16566357
TI  - [Education for the Nursing Service].

PMID- 16566358
TI  - [Recommendations of the Polish Society of Obstetrics and Gynecology for women
      urinary incontinence]].

PMID- 16566360
TI  - [Prophylactics of cervical cancer in Polish female population aged 45-54].
AB  - OBJECTIVES: The study was designed to evaluate the effectiveness of cervical
      cancer prophylactics by identification of the time of last cervical cytological
      examination as well as by recognition of frequency of repeated cervical
      cytological examinations and reimbursement for the examination costs in
      representative sample of Polish women aged 45-54. MATERIAL AND METHODS: The study
      was conducted with the use of a standardized questionnaire in April 2004 in
      Polish nation-wide representative sample of 1083 women selected by random-route
      method. The study was adjusted for the following controllable variables: age,
      place of residence and its number of inhabitants, province. RESULTS: For the last
      3 years cytological examination of cervical smear has been performed in 58% of
      women regardless of their age and education including 32% for the last year.
      Between 3 and 10 years ago the examination had been performed in 16% of women. As
      many as 14% of respondents admitted that they had never had this examination. 5%
      declared having the examination more than 10 years ago, 4% could not remember
      having this examination at all and the remaining women either were not aware of
      this examination or did not answer this question. Cervical cytological
      examinations repeated regularly every 12-18 months were declared by 30% of women.
      Regular cervical cytological examinations were performed significantly more often
      among women using hormonal replacement therapy (54%) and those living in big
      cities (44%). These examinations were free of charge for 823 of women.
      CONCLUSIONS: Considerable proportion (42%) of women aged 45-54 years have not had
      cervical cytology performed for the last 3 years. More than a half of them (23%)
      do not care about their health and are not aware how important this examination
      is. As few as 30% of women have regular cytologic examinations. These are more
      often women interested in hormonal replacement therapy and big city dwellers.

PMID- 16566359
TI  - [Gastrointestinal stromal tumors localized in small intestine and diagnosed
      preoperatively as gynecological neoplasms].
AB  - OBJECTIVES: The aim of the study was the analysis of women with gastrointestinal
      stromal tumors (GIST) of small intestine treated and followed-up in Cancer Center
      Institute in Warsaw, who were primary operated in gynecological departments due
      to suspicion of gynecological neoplasm. MATERIALS AND METHODS: In the database of
      Clinical GIST Registry from 2001 to 2004 we identified 44 women with the
      diagnosis of CD117(+) GIST of small intestine, what corresponds to 34% (44/130)
      all female GIST patients. Sixteen of them (36.4%, 16/44) were primary operated on
      in gynecological departments due to the tentative diagnosis of gynecological
      neoplasm. RESULTS: The only indication for operation in 29 women was undiagnosed
      microscopically tumor of the pelvis. Sixteen of them (55.2%, 16/29) were operated
      on schedule in gynecological departments. The others 15 patients were operated
      due to: ileus and perforation of digestive tract (8), gastrointestinal bleeding
      (3), abdominal pain (2) and others (2). In analyzed group of patients 20 women
      (45.5%) after GIST excision remain without evidence of disease with median follow
      up time of 9 months, and in 24 patients (54.5%) GIST recurred in median time of
      18.5 months. In this latter group 23 patients were treated with imatinib due to
      inoperable/metastatic lesions. Estimated 2-year overall survival (calculated form
      the date of imatinib introduction) was 75%. CONCLUSIONS: GISTs, especially of
      small intestine, may simulate in women gynecological tumor, particularly of the
      ovary. Radical surgery remains the most effective method of GIST treatment. In
      inoperable/metastatic lesion the treatment of choice is tyrosinase kinase
      inhibitor--imatinib.

PMID- 16566361
TI  - [Screening mammography in Polish female population aged 45 to 54].
AB  - OBJECTIVES: The objective of the study was to investigate the time of last
      screening mammography as well as frequency of regular mammography examinations in
      Polish female population aged 45 to 54. MATERIAL AND METHODS: The study,
      conducted in April 2004, included Polish nation-wide representative random sample
      of 1083 women. The study was adjusted for controllable variables including age,
      type and size of place of residence, province. RESULTS: As few as 47% of women
      underwent screening mammography during the last three years. Mammography was
      performed significantly more often in big city dwellers than in women from
      small/moderate towns and villages (64% versus 43% and 40%, respectively).
      Mammography had never been performed in 39% of women including every other woman
      with primary/vocational education, every third woman with secondary education and
      every fourth woman with university education. Mammography is repeated on regular
      basis every 12-18 months in 19% of women. Older women (50-54 years old) are
      significantly more numerous--24% in this group than younger ones (45-49 years
      old)--15%. Amongst regular mammography users there are more big city dwellers-
      34% versus women from small/moderate towns--16% and from villages--14%, as well
      as there are more women with higher education level--women with university
      education constitute 30% of this group versus 23% of women with secondary
      education and 11% of women with primary/vocational education. Current and past
      users of hormonal replacement therapy, as well as women who are going to use HRT
      in the future significantly more often attend screening examinations. CONCLUSION:
      There is a strong need for development and implementation of a screening
      mammography program. National guidelines concerning the age of the first
      screening mammography and recommended frequency of mammography examinations
      during subsequent decades of woman's life should be developed. Educational
      campaigns are needed that would be designed not to frighten the women but to
      encourage them for regular use of screening mammography and to make them aware of
      the huge role mammography plays in detecting early stages of breast cancer and
      reducing women's mortality.

PMID- 16566362
TI  - [Chlamydia trachomatis and human papillomavirus (HPV) infections in teenage
      sexually active girls].
AB  - OBJECTIVE: The purpose of the study was to determine the frequency of
      C.trachomatis and HPV infections in teenage, sexually active girls. MATERIAL AND
      METHODS: 48 non-pregnant, sexually active young women (between 16-19 years of
      age), who submitted for periodical check-up during oral contraceptive use.
      Patients had periodical mild pain in the lower abdominal area and increased
      amount of mucigenous secretion. They had their first sexual intercourse before 16
      years of age, multiple partners (>3), unprotected intercourse. The direct
      immunofluorescence (DIF) was used for C. trachomatis antigen detection (Chlamydia
      Direct IF (bioMerieux, France). DNA HPV presence and oncogenic potential was
      assessed using hybridization method (Hybrid Capture I HPV Assay, Digene Corp.
      Beltsville, MD U.S.A.). RESULTS: C. trachomatis antigen was detected in 13 aut of
      48 swabs (27%), presence of HPV DNA was detected in 2 teenage girls with normal
      cytology (4.2%). In cytological evaluation LSIL (low grade squamous
      intraepithelial lesions) was described in 5 cases. In 4 of them along with LSIL
      coexisted C. trachomatis infection.

PMID- 16566364
TI  - [Prenatal diagnostics of congenital heart disease--own results].
AB  - OBJECTIVES: Congenital heart defects (CHD) are the most common congenital
      malformation. They are still often overlooked in fetuses during the routine
      obstetric scanning. DESIGN: The aim of our study was to present our results in
      detecting CHD in high risk pregnancies. MATERIAL AND METHODS: The echocardiograms
      of 135 fetuses and case history of neonates who had prenatal diagnosis of CHD
      were revied retrospectively. RESULTS: We diagnosed CHD in 135 fetuses. The most
      common CHD were: atrio-ventricular canal (32 fetuses-23,7%), hypoplastic left
      heart syndrome (17 fetuses--12.6%), ventricular septal defect (11 fetuses--8.2%),
      and aortic stenosis (10 fetuses--7.4%). There were 15 intrauterine deaths (11.1%)
      and 8 neonatal deaths. CONCLUSIONS: Prenatal echocardiography enables early
      detecting and adequate treatment of congenital heart defects.

PMID- 16566363
TI  - [Safety evaluation of a transdermal contraceptive system with an oral
      contraceptive].
AB  - OBJECTIVE: evaluation of the frequency of adverse events during the therapy with
      a transdermal contraceptive system (TCS) in comparison to an oral contraceptive.
      MATERIAL AND METHODS: 20 healthy women aged 23.8 +/- 4.1 years without
      contraindication to steroid hormonal therapy and a history of dermal
      hypersensitivity to adhesive applications. All patients were treated with either
      contraceptive patches containing 20 microg ethinyl estradiol (EE) and 150 microg
      norelgestromin (17-dNGM) or a monophasic oral contraceptive containing 20 microg
      EE and 150 microg desogestrel during 6 cycles. Safety evaluation was based on the
      frequency of adverse effects, changes in physical and gynecological examinations.
      RESULTS: The incidence of most adverse effects was similar between the
      transdermal and oral contraceptive therapies, except of a higher incidence of
      breast pain, dysmenorrhoea and application site reactions in the patch group. 50%
      of patients demonstrated gastro-intestinal complaints in the oral contraceptive
      group. None of the patients discontinued the hormonal contraceptive therapies due
      to adverse effects. CONCLUSION: The study suggests that a transdermal
      contraceptive system is a safe and well tolerated therapy.

PMID- 16566365
TI  - [Hairy cell leukemia in pregnancy].
AB  - Pregnancy complicated by HCL is an extremlely rare event: only 5 report of HCL in
      pregnancy have been previously described. A 36-year-old women was diagnosed of
      HCL presented in 14 week of her 5th pregnancy. Therapy was initiated in 18 wk of
      gestation with IFN-alpha at dose 6 x 106 U subcutaneous 3 times per week and
      prednisone 20 mg/d. IFN-alpha administration was well tolerated. After IFN-alpha
      therapy partial remission was achieved. The course of the pregnancy was normal.
      At week 39 of gestation a cesarean cection was performed and the patient
      delivered a healthy male infant weighing 3460 g with Apgar score of 10. The
      placenta was of normal size, no infiltration of hairy cell was founded. Post
      partum course was uncomplicated. The patient elected to not breast feed her
      infant. 3 weeks after delivery patient had a 5-days course of 2CDA

PMID- 16566366
TI  - [Didelphic uterus coexisting with bladder exstrophy].
AB  - Congenital anomalies of structures originating from Mullerian ducts are important
      gynecological problem. They often coexist with malformations of urinary tract. In
      this report we describe the case of 31 year old women with didelphus and bladder
      extrophy. The surgical treatment consisted on transabdominal total hysterectomy
      due to endometriosis IV (rAFS) narrowing ureteroenterostomy.

PMID- 16566367
TI  - [Gasless laparoscopic cyctectomy due to to ovarian cyst torsion in 14 weeks
      pregnant patient].
AB  - We present a case of gasless laparoscopic cystectomy due to ovarian cyst torsion
      in pregnant women. The course of an operation and postoperative period were
      uncomplicated. The gestation continued to term without any complication and the
      patient delivered an average-sized infant. We confirm that the gasless
      laparoscopy is a safe procedure for a certain group of pregnant women and allows
      to avoid laparotomy.

PMID- 16566368
TI  - [HELLP syndrome complicated by liver rupture].
AB  - The object of our study was the liver rupture as a complication of HELLP
      syndrome. We described a case of 27-year-old primigravida who underwent the
      cesarean section because of HELLP syndrome, followed by four laparotomies, due to
      capsular hematoma and liver rupture. Surgery with packing, argon coagulation or
      embolization of hepatic artery remain the only treatment for subcapsular hematoma
      and liver rupture. The main issue is to state the early diagnosis of HELLP
      syndrome because its clinical presentation at the beginning is very unclear and
      diagnosis is often delayed. It is important because the morbidity and mortality
      rates associated with the syndrome have been reported to be as high as 25
      percent.

PMID- 16566369
TI  - [Novel treatment for severe sepsis: recombinant human protein C (RHAPC)].
AB  - STUDY DESIGN: Review of literature on novel therapy for severe sepsis within
      recombinant human protein C (rhAPC). DATA SELECTION: MEDLINE and Polska
      Bibliografia Lekarska (2000-2003) were the main sources of the reviewed articles.
      DATA SYNTHESIS: Despite advances in critical care the rate of death from severe
      sepsis ranges from 30 to 50 percent (data related to patients with this
      complication treated in the intensive care units in the United States). In Poland
      about one third (27.3%) of all maternal deaths in 1991-2000 were from severe
      sepsis. Since the introduction of antibiotics, the first significant progress in
      effective therapy for severe sepsis was achieved due to the novel therapy within
      rhAPC. In 2001 Bernard et al. reported results of multi-center, placebo
      controlled, randomized trial, in which the administration of rhAPC at 24
      microgram/kg/h/96 hrs increased the survival in patients with severe sepsis by
      6.1% (mortality rate was 24.7% for rhAPC group, while 30.8% for placebo group).
      There was an insignificant tendency for more bleeding in rhAPC patients (3.5% vs.
      2.0% with placebo). In 2003 Dhainaut et al. described the pharmacological effects
      of rhAPC on severe sepsis. Fifteen biomarkers of inflammation or
      thrombosis/fibrinolysis were monitored. It was established that rhAPC decreases
      host response to infection resulting in lowering the levels of all inflammatory
      cytokines (TNFalfa, IL-1, IL-6 and IL-8), as well as lowering procoagulant
      markers, mainly D-dimers. CONCLUSION: Sufficient data are available to approve
      rhAPC for treatment of patients with severe sepsis. Both anticoagulant and
      antiinflammatory properties of rhAPC, as well as profibrinolytic activity, are
      the rationale for the use of rhAPC.

PMID- 16566370
TI  - [Classification and surgery for uterovaginal anomalies].
AB  - Maldevelopment of the mullerian ducts occurs in a variety of forms, and each
      anomaly is distinctive. Nevertheless, some generalizations can be made. A
      comprehensive preoperative evaluation of patients with suspected uterovaginal
      malformations is essential, but a clear understanding of the particular anomaly
      may not be established until the time of surgical correction. It is essential to
      exclude other then anatomical causes of procreative misfortunes before making the
      decision dealing with surgical correction of a given uterovaginal anomaly.

PMID- 16566371
TI  - [Physiological skin changes during pregnancy].
AB  - Associated with pregnancy skin changes appear at approximately 90% pregnant. For
      the necessity of proper and complex care of the pregnant woman. The actualization
      of this knowledge among the family doctors and the obstetricians is crucial. The
      ability of precise diagnosis of physiological skin changes allows specifying the
      suspected cases of pathologic etiology and referring them to the dermatological
      referral centers for in-depth diagnosis and eventual treatment. The physiologic
      changes of skin appendies were discussed in the presented paper, vascular
      alterations color, as well as the generative alterations and the changes in the
      skin.

PMID- 16566372
TI  - [Polish Gynecological Society's recommendations regarding pregnant women with
      diabetes mellitus].

PMID- 16566373
TI  - [Assessment of selected factors influencing birthweight in pregnant women with
      gestational diabetes mellitus].
AB  - OBJECTIVES: Giving birth to a chi;d with an excessive brithweight is one of the
      most common neonate complications observed in the pregnant women with gestation
      diabetes (GDM). DESIGN: The aim of the study was an evaluation of selected
      factors affecting birthweight in the GDM. MATERIALS AND METHODS: Data from 867
      pregnant women were analysed. The influence of: age, height, place of living and
      mother's educational background and BMI before pregnancy and weight gain during
      pregnancy and also HbA1c, triglycerides (TG) and total cholesterol (TC) values in
      the 3rd term of pregnancy (T3) were determined. The TC and TG were assessed by
      the enzymatic method by means of the Bio Merieux firm set--France, HbA1c by means
      of the immunoturbidimetric method using the Roche firm sets--France. RESULTS:
      Statistically significant birthweight differences were affirmed according to:
      mother's height (respectively the groups: < or = 155 vs 156-169 vs > or = 170
      cm), BMI before pregnancy (< 25 vs 25-29.9 vs > or = 30 kg/m2), weight gain in
      pregnancy (< 12 vs > or = 12 kg), TG (< 2.7 vs > 2.7 mmol/l) and HbA1c in T3. No
      influence of mother's age, her place of living, educational background, HbA1c at
      admission and TC values in T3 on the neonates birthweight was observed.
      CONCLUSIONS: The anthropometric and environmental factors (mother's height,
      weight, weight gain in pregnancy) have a more significant influence on the
      neonates birthweight of the mothers with GDM, than social-demographic factors
      (age, educational background, place of living), the way of treatment of GDM and
      TC in T3. The TG level in T3, beside HbA1c is an independent, prognostic factor
      of birthweight in GDM.

PMID- 16566374
TI  - [Retrospective evaluation of pregnancy in women suffering from systemic lupus
      erythematosus (SLE)].
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease
      predominantly affecting women of childbearing age, which may negatively influence
      the pregnancy course and outcomes. The objective of the study was to estimate the
      risk of fetal loss and prematurity in lupus patients. These data seem to be an
      important component of family counselling in lupus patients. DESIGN: The
      pregnancies' course and outcomes in lupus patients and in healthy controls were
      compared. MATERIAL AND METHODS: 47 lupus patients with pregnancies occurring
      after the diagnosis of SLE and 108 healthy controls were included in this study.
      The pregnancies were analysed in terms of delivery term and outcomes (live
      births/ miscarriage/ neonatal deaths/ congenital defects). The structured review
      and case histories analysis were used to gather the data. RESULTS: The percentage
      of spontaneous abortions (24.1%) and preterm deliveries (24.1%) were
      significantly higher in lupus patients when compared with healthy controls (9.3%
      and 5.3% respectively). CONCLUSIONS: The caution in pregnancy planning in lupus
      patients is necessary and the role of physicians' information in patients'
      awareness of fetal loss and prematurity is vital.

PMID- 16566376
TI  - [Maternal cardiac arrhythmias in pregnancy].
AB  - OBJECTIVES: Perinatal care of women with cardiac arrhythmias is very important
      for every obstetrician. Maternal heart disease complicates 0.2 to 4% of
      pregnancies. DESIGN: The purpose of this study was to analyze the course of
      pregnancy, delivery and postpartum period pregnant women with cardiac arrhythmias
      MATERIALS AND METHODS: We analyzed 14 pregnant women with cardiac arrhythmias.
      hospitalized in the Department of Obstetrics of Medical University of Gdansk,
      1998-2003. Time of delivery, weight and length of neonates in patients with
      cardiac arrhythmias was presented. RESULTS: Delivery and postpartum period were
      uncomplicated in all the patients and no stimulation was used. In two women with
      congenital complete atrio-ventricular block dicavital heart stimulator was
      applied. All patients and infants were discharged from hospital in good
      condition. CONCLUSION: We found no cardiological complications during pregnancy
      in patients with cardiac arrhythmias.

PMID- 16566375
TI  - [The effect of tobacco smoking during pregnancy on concentration of
      malondialdehyde in blood of mothers and in umbilical cord blood].
AB  - OBJECTIVES: Maternal smoking during pregnancy is known to be associated with not
      only intrauterine fetal growth retardation or low birth weight but also causes
      disturbances in postnatal growth and development. The prime role of oxidative
      stress in the pathogenesis of adverse pregnancy outcomes is almost universally
      accepted. DESIGN: The aim of the study was to estimate the effect of tobacco
      smoking during pregnancy on concentration of lipid peroxidation products
      (malondialdehyde - MDA) in blood of mother and newborns. MATERIALS AND METHODS:
      147 healthy, pregnant women were divided into non-smoking (n = 85) and smoking
      group (n = 62) according to questionnaire declaration and confirmed by cotinine
      concentration in serum and urine. Level of MDA was measured by fluorimetric
      method in plasma and in erythrocytes of mothers and umbilical cord blood.
      RESULTS: We found that, in group of women smoking during pregnancy concentration
      of malondialdehyde was higher in plasma and in erythrocytes when compared to
      group of tobacco abstinent. Also in cord blood of newborns of smoking mothers
      level of MDA was significantly higher in plasma (p < 0.05) as well as in
      erythrocytes (p < 0.01) than in control group. CONCLUSION: The presented results
      indicate that smoking during pregnancy may promotes free radical damage in
      growing fetus and newborns therefore stimulates metabolic disorders dependent on
      oxidative stress.

PMID- 16566377
TI  - [Attitude of pregnant women towards labour--study of forms of preparation and
      preferences].
AB  - OBJECTIVE: The aim of this study was to assess the knowledge of alternative
      delivery techniques among pregnant women and their preferences concerning the
      course of labour. MATERIAL AND METHODS: 275 woman hospitalizated in obstetric
      wards in Puck and Ist Clinic in Warsaw were questionnaired in the period of July
      2003 - February 2004. The mean age of women was 26 +/- 4.9. 55.7% of them were
      nulliparous, 44.3% multiparous. T-Student test was used for statistical analysis.
      RESULTS: The majority of questionnaired women knew alternative positions during
      delivery and possible analgetic techniques. 25.1% of women attended labour
      school. 81.2% wanted to give birth in the hospital, 10% at home and 8.8% in the
      delivery room. 51.1% preferred waterbirth and 22.5% obstetric chair--most of them
      came from the big cities, were better educated and attended labour school. Almost
      half of all women are in favour of epidural anaesthesia of delivery. Caesarean
      section on request was supported by 13.8%. For 67.4% the presence of intimates
      during labour was important. CONCLUSIONS: Labour school has a significant
      influence on women's knowledge and their preferences. Waterbirth and other modern
      delivery techniques are very popular among better educated women from big cities,
      while those with lower education from small cities and villages prefer "classic"
      labour. Therefore promotion of modern delivery methods and active participation
      in labour should be concentrated on these groups of women. Nowadays obstetric
      departments should ensure not only safety of giving birth but also complete
      personal comfort for pregnant women.

PMID- 16566378
TI  - [Pregnancy complications and pregnancy outcome in women under 18 and above 35
      years old in highly industrialized urban complex of Upper Silesia].
AB  - OBJECTIVES: There is a considerable effort done by many researchers towards
      identification factors that are responsible for increase in risk of adverse
      perinatal outcome. Maternal age is one of the most obvious but also one of the
      most difficult to proper interpretation. MATERIAL AND METHODS: The authors
      analyzed major complications in pregnancy and labour in women under 18 above 35
      years old in highly industrialized urban complex of Upper Silesia. RESULTS:
      Extremes of reproductive age, adolescence and age above 35 years have an impact
      on biological, social, cultural and economic conditions that significantly
      affects obstetrical results. CONCLUSIONS: Teenage mothers and the mothers above
      35 years old are regarded to be in increased risk of instrumental delivery and
      caesarean section. These factors are also associated with augmented incidence of
      complication such as preterm labour, intrauterine growth restriction etc.

PMID- 16566380
TI  - [The influence of body mass and stimulants on female fertility].
AB  - Infertility has been recognized by WHO a disease concerning males and females. It
      is a serious social problem, therefore the evaluation of its reasons, its
      prevention and treatment is a subject of clinical studies. OBJECTIVE: To define
      the reasons of infertility and factors affecting fertility. MATERIAL AND METHOD:
      The studied group consisted of 438 women, aged 21-46 years (average 29.7),
      suffering from primary or secondary infertility, treated at Gynecological
      Endocrinology Department of Medical University in Warsaw between January 1999 and
      March 2003. The data was obtained from medical records and interviews. The
      following factors were analyzed: body mass index (BMI), the kinds of stimulants
      and the type of infertility. RESULTS: The primary infertility was diagnosed in
      292 women (66.7%), secondary in 146 (33.3%). According to BMI, 32 (8.6%) women
      were obese. 102 patients (25.4%) were cigarette smokers. CONCLUSION: The factors
      affecting fertility are: obesity and cigarette smoking.

PMID- 16566379
TI  - [The influence of socioeconomic factors on female fertility].
AB  - OBJECTIVE: To define causes of female infertility and socioeconomic factors
      affecting fertility. MATERIAL AND METHODS: The study group consisted of 438
      patients, aged 21-46 (average 29.7), treated because of primary or secondary
      infertility between January 1999 and March 2003 at Gynecological Endocrinology
      Department of Medical University of Warsaw. All of them were residents of
      mazovian province. The following factors were analyzed: age, marital status,
      place of residence, education and the type of job performed in regard to their
      influence on fertility. The socioeconomic characteristics and the distribution of
      infertility in each age group were presented. RESULTS: Fifty women were aged over
      35 (11.4%). Most of the examined patients were city residents--339 (80%). 182
      (43.5%) women had university education, 189 (45.2%)--secondary education. 76
      (18.5%) women were physical workers. The factors affecting fertility were: age,
      education and the type of work performed. CONCLUSION: Age over 35 years and
      intensive physical work are the factors affecting fertility.

PMID- 16566381
TI  - [Primary headache associated with sexual activity].
AB  - Benign coital headache is known as a rare type of primary headache related to
      sexual activity. The pathogenesis of this type of headache remains unknown.
      Clinical manifestation is typical and connected with three phases of sexual
      activity. Coital cephalalgia is divided into two subtypes: preorgasmic and
      orgasmic headache. Some authors specifie the third type--postural type.
      Preorgasmic headache starts as a dull bilateral ache and increases with sexual
      excitement. Orgasmic headache has sudden, intense character and occurs at orgasm.
      Postural headache has been reported to develop after coitus. The author describes
      four cases of different types of sexual headache, which were effectively treated.
      Indomethacin was effective in all patients as direct treatment and propranolol
      was effective in patients to whom it was administrated as preventive treatment.

PMID- 16566382
TI  - [Women's sexual life quality assessment with use of questionnaires in clinical
      trials--review of accessible tools, their characteristics and comparison of their
      properties].
AB  - AIM: Aim of the study is a review of women's sexual life quality assessment
      questionnaires available in literature, analysis of their construction, special
      properties and usability in clinical trials. MATERIAL AND METHODS: Medline
      database and accessible literature has been reviewed. Seven questionnaires have
      been chosen for analysis. Analysis in scope of potential and usability of those
      questionnaires in clinical tests has been performed. CONCLUSIONS: Suitability of
      The Female Sexual Function Index (FSFI) and The Brief Index of Sexual Functioning
      for Women (BISF-W) have been shown as universal tools for sexual function
      assessment in clinical trials. They meet current model of women's sexual reaction
      and criteria of sexual disfunction classification.

PMID- 16566383
TI  - [The diagnosis of hyperprolactinemia in clinical practice].
AB  - Prolactin is a pituitary hormone that plays pivotal role in a variety of
      reproductive functions. Hyperprolactinemia is a common condition that can result
      from a number of causes; including use of medications and hypothyroidism, as well
      as pituitary disorders. Depending on the cause and consequences of
      hyperprolactinemia, selected patients require specific treatment. The underlying
      cause of hyperprolactinemia, sex, age and reproductive status must be considered.
      Management of this condition depends heavily on the cause and on the effects it
      has on the patient. The definition of the hyperprolactinemia is not uniformed,
      and in various clinical settings various criteria of this status are used. In the
      identification of hyperprolactinemia not only simple measurements of the
      prolactin serum level are used, the dynamic tests with the use of dopamine
      antagonists have a special role as well. Neither the measurement of the serum
      prolactin level, nor dynamic tests with dopamine antagonists are able to
      determine the presence of macroprolactin molecules in the serum, and this can
      lead clinicians to establish the false diagnosis of hyperprolactinemia.

PMID- 16566384
TI  - [The most frequent ear problems in general practice. Can you see that your
      patient is hard-of-hearing?].

PMID- 16566385
TI  - [Weight loss, weakness and round foci in the liver. Liver metastases, what
      else?].

PMID- 16566386
TI  - [What do your patients want to know now? The most frequent questions about avian
      influenza].

PMID- 16566387
TI  - [Pimples and pustules have various causes. Acne reveals the muscle builder].

PMID- 16566388
TI  - [The numbers of patients with endocrine disorders are increasing. Who will be
      responsible for them in the future?].

PMID- 16566389
TI  - [Subclinical hypothyroidism--what level of TSH is an indication for
      substitution?].
AB  - Overt hypothyroidism is always an indication for substitution with levothyroxine.
      In patients with subclinical hypothyroidism and clearly elevated TPO antibodies,
      a wish to bear a child, infertility, and pregnancy, as also hypothyroidism
      associated symptoms, including depression, a trial substitution with
      levothyroxine is justified. Before long-term treatment is initiated, an
      improvement in the clinical symptoms must be confirmed. Even though levothyroxine
      reduces the LDL cholesterol, or other risk factors are improved, it has not so
      far been unequivocally shown that levothyroxine reduces morbidity and mortality.
      These questions should be investigated in prospective clinical studies.

PMID- 16566390
TI  - [Subclinical Hyperthyroidism--What is Expected of the General Physician?].
AB  - Subclinical hypothyroidism is usually diagnosed during a routine examination. The
      results of recent studies reveal it to be a significant disease that is
      associated with a negative impact on myocardial function, an increased incidence
      of atrial fibrillation in the elderly patient, a loss of bony substance in post
      menopausal women, and, possibly, an increased incidence of dementia in the
      elderly. Associated with this pathology is also a significant increase in the 10
      year mortality rate. All this points to an urgent need to determine the
      underlying cause of sub-clinical hypothyroidism and to treat the condition in
      thesame way as manifest hyperthyroidism.

PMID- 16566391
TI  - [Current treatment with oral antidiabetic agents].
AB  - In the large majority of type 2 diabetics, the initial phase of the disease is
      characterized by insulin resistance. A primary insulin secretion disorder is seen
      only in normal-weight patients, and requires a differentiated therapeutic
      approach. Glinides make possible flexible meal-oriented stimulation of insulin
      secretion. Insulin resistance can be influenced by insulin sensitizers. In the
      overweight patient, biguanides (metformin) effectively lower blood sugar, either
      alone or in combination with other oral antidiabetic agents. Acarbose, and
      glitazone can delay progression to diabetes. Furthermore, acarbose, biguanides,
      and in particular glitazone, reduce cardiovascular events. For normal-weight
      patients, sulfonylureas are considered the first-line drug for monotherapy.
      Progressive insulin secretion deficiency and usually persistent insulin
      resistance requires insulin substitution in combination with oral antidiabetic
      agents or as conventional/intensified insulin therapy.

PMID- 16566392
TI  - [Pharmacotherapy in the treatment of obesity].
AB  - Currently, the substances orlistat and sibutramine are approved drugs for the
      pharmacotherapy of obesity. Used in combination with increased exercise and
      dietary measures, both are capable of significantly reducing weight. In the USA
      and Europe, official approval for the selective cannabinoid receptor antagonist,
      rimonabant has been applied for.

PMID- 16566393
TI  - [Cold extremity with no palpable pulse. Place it in a dependent position on a
      soft support, administer intravenous heparin!].

PMID- 16566394
TI  - [Do you work already with the newest insurance refund list?].

PMID- 16566395
TI  - [So young and apoplexy already].

PMID- 16566396
TI  - [Which prevention methods do you recommend to her?].

PMID- 16566397
TI  - [Monster hernia].

PMID- 16566398
TI  - [Oral health care in nursing and old people's homes and institutions for the
      mentally handicapped].
AB  - Staff members and residents of nursing homes and old people's homes were
      interviewed about the facilities and provision of oral health care. Clinical
      examinations were performed to obtain data about the oral health status of the
      institutionalised elderly. Results show that in most cases the oral health care
      facilities were insufficient to give care to persons with natural teeth. Of the
      edentulous elderly 43% reported that the retention of the lower denture was
      insufficient.

PMID- 16566399
TI  - [Bone anchorage in orthodontics. A review].
AB  - The achievement of absolute anchorage in orthodontics overcoming the reaction
      forces and moments has been problematic for a long time. This was caused on the
      one hand by the limitations of the devices available and on the other hand by the
      dependence on patient cooperation. The introduction of bone anchorage systems
      changed the traditional way of thinking on orthodontic anchorage. Whereas the
      application of anchor systems, such as palatal implants and onplants, has
      specific indications, bone screws with or without plates seem to have the
      potential of being used on a routine basis. However, appropriate data for more
      complete understanding of the biological and biomechanical background of this
      concept of orthodontic anchorage are still lacking. Furthermore, studies on the
      effectiveness of these systems when compared to the traditional orthodontic
      anchorage and based on large groups of patients are not available. Well-designed
      prospective clinical trials substantiating the evidence-based use of these
      devices are needed.

PMID- 16566400
TI  - [The changing picture of practicing dentistry].
AB  - Originally, dentists were particularly technical and curative practitioners.
      Nowadays, patient care is brought into focus, directed at maintaining oral health
      permanently by prevention and necessary curative treatments as a contribution to
      general health and well-being. The changing picture of praccising does not
      develop as a matter-of-course since many factors have an effect on dental
      practice. Effecting factors are: content concerning developments, technological
      advancements, legislation, government policies, organizational aspects, and
      typical characteristics of dental practitioners. The changing picture of
      practising dentistry is connected with uncertainty, proves to be hard to control,
      and some adjustments occur around practising.

PMID- 16566401
TI  - [Dental records and responsibility].
AB  - Dental records are more than a small part of the bookkeeping. In most dental
      practises, keeping records is the task of a dental assistant. In civil court, the
      dentist is in most countries liable for the mistakes of his employees. In
      disciplinary court however there may be doubt whether the dentist is responsible
      for the mistakes of his assistant. Contrary to their American colleagues, Dutch
      dental assistants and dental hygienists cannot be summoned before a disciplinary
      court. As these para-medics perform more and more dental treatment, independently
      or after delegation, they should be assigned there own disciplinary
      responsibility.

PMID- 16566402
TI  - [Cheek swelling after surgical removal of third molar].
AB  - A 55-years-old man visited his family doctor because of a one-day existing, not
      painful, right-sided swelling of the cheek. It appeared to be a subcutaneous
      emphysema, caused at an attempt to remove mandibular third molar roots, using a
      water- and air-cooled air rotor. Rare potential seuelae resulting from
      subcutaneous emphysema are venous air embolism, airway obstruction because of
      neck swelling, pneumomediastinum, and mediastinitis. Using air-cooled instruments
      in surgical orofacial treatments should be avoided because of the possible
      atrogenic life-threatening complications.

PMID- 16566403
TI  - [Acute sialoadenitis of the parotid gland].
AB  - An 88-year-old diabetic women was hospitalized because of a pheripheral vascular
      disorder. During her hospitalization she developed a right-sided facial swelling
      which was not limited by anatomical structures in this area. Ultrasound and
      computertomographic scanning supported the clinical diagnosis acute sialoadenitis
      of the parotid gland. The swelling resolved shortly after starting antibiotic
      therapy.

PMID- 16566404
TI  - Stress echocardiography in the evaluation of exercise physiology in patients with
      severe arterial pulmonary hypertension. New methodology.
AB  - INTRODUCTION: Doppler echocardiography is usually performed when assessing a
      patient with severe pulmonary hypertension (PHT), since it enables accurate
      determination of the severity of the hypertension through evaluation of several
      morphologic and hemodynamic variables. Echocardiograms are usually performed in
      left lateral decubitus (LLD). However, symptoms often arise only in a standing
      position and particularly during exercise. OBJECTIVE: To evaluate a group of
      patients with severe PHT using Doppler echocardiography during treadmill exercise
      testing. METHODS: We studied 8 patients (group A), mean age 43.88 +/- 14 years, 7
      women; three had idiopathic pulmonary hypertension, 2 pulmonary thromboembolic
      disease, 2 Eisenmenger syndrome, and one pulmonary hypertension associated with
      celiac disease. We also studied an 8-patient control group (group B) with similar
      demographic characteristics, who had tricuspid regurgitation but no known cardiac
      disease, including pulmonary hypertension (excluded by echocardiogram). In
      addition to the ergometric variables of stress test duration using the modified
      Bruce protocol, resting heart rate, peak heart rate (PHR), resting systolic blood
      pressure (RSBP) and peak systolic blood pressure (PSBP), we evaluated the
      following echocardiographic variables: pressure gradient between right ventricle
      and right atrium (RV/RAg) and systolic volume (SV) in left lateral decubitus, in
      a standing position (SP) and at peak workload (PW). Stress testing was stopped in
      cases of fatigue and/or dyspnea. RESULTS: In group A, the RV/RAg in LLD was 100
      +/- 20 mmHg, 98 +/- 20 mmHg in SP (p = NS) and 129 +/- 27 mmHg at PW (p = 0.003
      vs. SP). In group B, the RV/RAg in LLD was 19.8 +/- 3.5 mmHg, 14.6 +/- 2.1 mmHg
      in SP (p = 0.0005) and 29.5 +/- 3.3 mmHg at PW (p < 0.0001 vs. SP). In group A,
      SV was 38 +/- 11 ml in LLD, 35 +/- 10 ml in SP and 32 +/- 9 ml at PW (p = NS); in
      group B, it was 63 +/- 5 ml in LLD, 55 +/- 5 ml in SP and 64 +/- 7 ml at PW (p <
      0.0001). PHR was 114 +/- 10 bpm in group A and 145 +/- 8 (p < 0.0001) in group B.
      RSBP was 113 +/- 13 mmHg and PSBP 112 +/- 21 mmHg (p = NS) in group A, and 116 +/
      18 mmHg and 161 +/- 25 mmHg respectively (p < 0.0001) in group B. In four
      patients from group A, symptomatic falls in systolic blood pressure and SV
      occurred at PW. During a mean follow-up of 27 months (between 6 and 44 months),
      two of these four patients died and one is awaiting lung transplantation.
      CONCLUSIONS: 1. RV/RAg did not diminish in the standing position and rose
      significantly with orthostatic isotonic exercise during exercise testing in
      patients with severe PHT, with pulmonary artery systolic pressure reaching
      suprasystemic values. 2. Systolic volume and systolic blood pressure did not rise
      during exercise in patients with severe PHT, and patients with a decrease in
      systolic volume had worse clinical evolution. 3. Patients with severe PHT
      appeared to have chronotropic incompetence during exercise compared to the
      control group.

PMID- 16566405
TI  - Hypertrophic cardiomyopathy in a Portuguese population: mutations in the myosin
      binding protein C gene.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart
      disease and is often a consequence of mutations in the myosin-binding protein C
      gene (MYBPC3). Until now, however, no systematic review has been published on
      mutations of this gene in a Portuguese population. OBJECTIVES: In a Portuguese
      population of HCM patients: 1) to determine the prevalence of mutations in the
      MYBPC3 gene; 2) to characterize the mutations genetically; 3) to analyze the
      phenotype and compare it with the genotype-phenotype correlations for mutations
      in this gene described in the literature. METHODS: We studied 45 consecutive
      index patients with HCM (41 with familial HCM). In each patient, we performed a
      genetic study to detect mutations in the MYBPC3 gene. Once a mutation was
      identified and genetically characterized, a broad phenotypic evaluation was
      performed. The genetic and clinical data were then compared with those described
      in the literature. RESULTS: Of the 45 patients, 5 (11.1%) showed mutations in the
      MYBPC3 gene (2 deletions and 3 missense mutations), all in patients with familial
      HCM. Of these, 4 were 'new' mutations: Ala 522 Thr (exon 17); Gli 1205 Asp (exon
      32); Lis 505 Del (exon 17) and Lis 813 Del (exon 25). The other mutation, Arg 502
      Gln (exon 17), had been previously described in the literature. Three of the 5
      mutations were located in exon 17. Four of these 5 patients were symptomatic,
      mainly with heart failure and supraventricular arrhythmias. No patient was at
      high risk for sudden cardiac death. Most of the patients had non-obstructive HCM.
      The ECG, echocardiogram, Holter monitoring and treadmill exercise test showed
      highly variable results, reflecting the heterogeneity typical of this disease.
      CONCLUSIONS: In a Portuguese population of 45 HCM patients, 5 (11.1%) had
      mutations in the MYBPC3 gene (3 missense mutations--theoretically less frequent
      in the MYBPC3 gene--and 2 deletions). Four of these were 'new' mutations and 3 of
      them were located in exon 17 (which may be a 'hot spot' for MYBPC3 gene mutations
      in the Portuguese population). In all the patients, the phenotypic expression was
      different from that usually described for these mutations; in 3 of our patients,
      the clinical manifestations and penetrance were of early onset and one patient
      had a highly symptomatic form of obstructive hypertrophic cardiomyopathy. These
      data reflect the large number of exceptions to the classic genotype-phenotype
      correlations in HCM, highlighting the role of other factors, genetic and non
      genetic, in regulating penetrance, clinical expression and prognosis in each
      family and in each individual patient.

PMID- 16566406
TI  - The enigmatic diversity of hypertrophic cardiomyopathy.

PMID- 16566407
TI  - Usefulness of low-dose dobutamine echocardiography in idiopathic dilated
      cardiomyopathy.
AB  - INTRODUCTION: Low-dose dobutamine stress echocardiography is a common and useful
      technique to assess myocardial viability in patients with ischemic
      cardiomyopathy. OBJECTIVE: To evaluate the use of low-dose dobutamine stress
      echocardiography in determining the functional status of patients with idiopathic
      dilated cardiomyopathy (IDCM). METHODS: Prospective study of 28 patients with
      IDCM by transthoracic echocardiography (2D), low-dose dobutamine stress
      echocardiography, cardiopulmonary exercise testing (CPET) and measurement of pro
      BNP. RESULTS: The mean age of the population was 50.3 +/- 11.5 years, 9 female
      and 19 male. Mean ejection fraction was 32.1 +/- 9.8%. All were in sinus rhythm.
      The following parameters were analyzed in 2D echocardiography and after
      dobutamine: dimensions of left atrium (LA) and of left ventricle in diastole and
      systole, shortening fraction (%), left ventricular end-diastolic (EDV) and end
      systolic volumes (ESV), ejection fraction (EF), and mitral inflow (E, A, E/A
      ratio and deceleration time). In CPET, we considered the following parameters:
      peak VO2 and % maximal peak VO2 attained. We compared echo results with CPET.
      There was a correlation between age and peak VO2 (r = -0.38 with p = 0.049). In
      2D echo, there was a correlation between baseline EF and LA dimensions and peak
      VO2 (r = 0.45 / p = 0.004 and r = -0.49 / p = 0.014, respectively). After
      dobutamine echo, there was a correlation between some echo parameters and peak
      VO2: EF - r = 0.59 / p = 0.001, LA dimensions - r = 0.56 / p = 0.007, and ESV - r
      = -0.45 / p = 0.026. Percentage maximal peak VO2 attained correlated with LA
      dimensions measured in 2D echo and after dobutamine (r = -0.398 / p = 0.036 and r
      = -0.674 / p = 0.02 respectively) and EF after dobutamine (r = -0.389 / p =
      0.04). The value of pro-BNP correlated with LA dimensions and baseline EF (r =
      0.44 / p = 0.02 and r = -0.57 / p = 0.002, respectively), and the correlation was
      maintained after inotropic stimulation with dobutamine (r = 0.57 / p = 0.001 and
      r = -0.55 / p = 0.0039). CONCLUSION: Low-dose dobutamine stress echocardiography
      showed stronger correlations with cardiopulmonary exercise testing than the
      parameters evaluated by conventional echocardiography and could be used to
      determine the functional status of patients with dilated cardiomyopathy; patients
      with greater ejection fraction after inotropic stimulation had better
      cardiopulmonary tests.

PMID- 16566408
TI  - Cardiac tumors in the pediatric age group--case reports.
AB  - We present two case reports of primary cardiac tumors diagnosed in the pediatric
      age group, with different clinical evolution and therapeutic approach.

PMID- 16566409
TI  - Primary amyloidosis as a cause of microvascular angina and intermittent
      claudication.
AB  - Primary systemic amyloidosis or AL amyloidosis is a rare condition characterized
      by extracellular deposits of fibrils composed of fragments of immunoglobulin
      light chains. Widespread deposition of this amyloid in tissues interferes with
      their normal function and leads to multiple organ failure. Clinical
      manifestations are highly variable due to the wide range of organs involved. The
      heart is affected in 90% of cases; in 30% of these, cardiac dysfunction is the
      form of presentation and in 50% it is the cause of death. The commonest form of
      cardiovascular manifestation is congestive heart failure due to restrictive
      cardiomyopathy caused by extensive interstitial infiltration of amyloid into the
      myocardium. Occasionally, it can present as angina, due to infiltration of
      amyloid into the walls of small vessels. The authors describe the case of a
      patient in whom the disease presented simultaneously with heart failure and
      effort angina, as well as intermittent claudication.

PMID- 16566410
TI  - Types of clinical studies. IV. Clinical trials.
AB  - Clinical practice should be based on the best available information from high
      quality studies. Among the various study models, the randomized controlled trial,
      despite some disadvantages, is usually considered the gold standard for
      determining the efficacy of an intervention (drugs, surgery, etc.), and so this
      type of study should be part of all rational, conscious clinical decision-making.
      In this article, we present the classic structure of a randomized controlled
      trial, together with indications for critical appraisal of quality, as well as a
      brief discussion of the design, conduct and results, for correct determination of
      an intervention's effect.

PMID- 16566411
TI  - Stents for correction of aortic coarctation in adults.

PMID- 16566412
TI  - [Young children with serious disorders as a result of late diagnosis of cystic
      fibrosis].
AB  - A girl and a boy, who both presented with recurrent respiratory infections from
      birth, were referred to a paediatrician at the age of 2.5 years: they were
      diagnosed with cystic fibrosis (CF). The girl died from respiratory insufficiency
      at the age of 6 years and the boy at the age of 13 years from pulmonary
      aspiration. A further girl and boy who presented with abnormal faeces and failure
      to thrive were referred to the paediatrician at the ages of 2.5 months with
      haematomas and 2 weeks with anaemia respectively, as a result of vitamin
      deficiencies due to malabsorption. They too had CF. The girl had a brain
      haemorrhage in the meantime that left her with serious impairments. The boy
      recovered. A delay in diagnosing CF is not uncommon, as the symptoms of CF are
      hard to differentiate from those of common childhood diseases. However, this
      diagnostic delay can result in serious organ damage. Current treatment of CF has
      a predominantly prophylactic character and aims at maintaining normal growth and
      nutritional status as well as at preventing or postponing chronic bacterial
      infection of the lower respiratory tract. This treatment is most effective when
      it is started before any organ damage has occurred: a state that can only be
      achieved when patients with CF are identified shortly after birth. Therefore, it
      is important to add CF-screening to the neonatal screening program.

PMID- 16566413
TI  - [Cholinesterase inhibitors in dementia: the precarious balance between efficacy
      and safety].
AB  - Cholinesterase inhibitors are widely prescribed in patients with Alzheimer's
      disease. Recently it has become clear that using these medications increases the
      risk of serious adverse events like cardiac arrhythmias, and some studies report
      a much-increased mortality in the treatment group on comparison with the placebo
      group. In the light of the at best, modest, treatment effects, we advocate that
      the safety of cholinesterase inhibitors should be the subject of continuing,
      intense scrutiny. Efforts should be made to delineate the profile of a true
      'cholinergic deficiency syndrome', in order to be able to prescribe these
      medications to a group of patients in whom the benefits outweigh the risks.

PMID- 16566414
TI  - [Susceptibility to infection in patients with diabetes mellitus].
AB  - A variety of possible mechanisms that might explain such susceptibility are
      described in the literature. Still, definite explanations for and actual proof of
      this supposed susceptibility remains scarce. Most evidence has been provided for
      urinary tract infections, bacterial skin infections, and skin and mucosal Candida
      infections. A recent Dutch study among patients presenting to general
      practitioners provides further evidence for the increased susceptibility to this
      kind of infections, but also revealed a more frequent occurrence of lower
      respiratory tract infections and other skin or mucosal mycotic infections.
      Furthermore, there was an increased risk of prostatitis.

PMID- 16566415
TI  - [Potential role for probiotics in the prevention of infectious complications
      during acute pancreatitis].
AB  - Acute pancreatitis has a high mortality in case of secondary infection of (peri
      )pancreatic necrosis. Bacterial translocation is held responsible for the
      majority of these infectious complications of severe acute pancreatitis.
      Prophylactic strategies should therefore be directed at the three most important
      pathophysiological mechanisms of bacterial translocation: disturbed small-bowel
      motility and bacterial overgrowth, failure of the mucosal barrier function and a
      disturbed response of the immune system. In-vitro studies and research in
      experimental animals have shown that specially selected probiotics exert an
      effect on these mechanisms and can prevent bacterial translocation. Recently,
      several randomised, double-blind, placebo-controlled trials evaluating
      prophylactic treatment with enteral probiotics have shown good results. A Dutch
      multicentre trial, 'Probiotics in pancreatitis trial' (PROPATRIA), is currently
      underway.

PMID- 16566416
TI  - [Non-antibiotic prophylaxis for recurrent urinary-tract infections].
AB  - Urinary-tract infections (UTIs) occur frequently and hence have significant
      financial implications. Antibiotic prophylaxis can be considered in women with
      recurrent UTIs. However, frequent exposure to antibiotics can lead to
      antimicrobial resistance and side effects. The most important steps in the
      pathogenesis of UTIs are the colonisation and adherence of uropathogens.
      Lactobacilli impede intravaginal colonisation by competing with uropathogens.
      Cranberries interfere with the adherence of uropathogens to uroepithelial cells.
      Therefore, cranberries and lactobacilli are potential alternatives in the
      prophylaxis of UTIs. Randomised clinical trials comparing these compounds with
      long-term, low-dose antibiotics for the prevention of recurrent UTIs in women
      have not yet been conducted. Such a trial has recently been started in The
      Netherlands: the 'Non-antibiotic versus antibiotic prophylaxis for recurrent
      urinary-tract infections' (NAPRUTI) study.

PMID- 16566417
TI  - [Diagnostic image (265). A toddler with progressive abdominal pain after a car
      accident].
AB  - A 2.5-year-old boy who was caught in a car accident had a seatbelt-sign on his
      right lower abdomen and a jejunal perforation.

PMID- 16566418
TI  - [From the Cochrane Library: postmenopausal hormone replacement therapy (HRT) does
      not protect women against cardiovascular disease but does lead to an increased
      risk of venous thromboembolism].
AB  - Observational studies in the early nineteen-nineties have strongly suggested that
      hormone replacement therapy (HRT) has benefits for reducing cardiovascular events
      in postmenopausal women. A recent Cochrane systematic review assessed the effects
      of HRT in primary and secondary prevention of cardiovascular disease in
      postmenopausal women from ten randomized placebo-controlled trials published in
      the last decade. No protective effect of HRT was seen for any of the
      cardiovascular outcomes assessed. In contrast, higher risks of venous
      thromboembolic events, pulmonary embolus and stroke were found in postmenopausal
      women randomized to HRT compared to a placebo. Initiating HRT in postmenopausal
      women (with or without cardiovascular disease) for the sole reason of preventing
      cardiovascular disease should not be recommended. Further, in the case of other
      risk factors for venous thromboembolic events, the use of HRT for preventive
      purposes should be discouraged.

PMID- 16566419
TI  - [Increased risk of infection in patients with diabetes mellitus type 1 or 2].
AB  - OBJECTIVE: To determine the risk of common infections in patients with diabetes
      mellitus type 1 (DM1) or type 2 (DM2). DESIGN: Prospective controlled study.
      METHODS: In a 12-month prospective cohort study as part of the Second Dutch
      National Survey of General Practice, 705 adult DM1 and 6,712 DM2 patients were
      compared with 18,911 control patients who had hypertension without diabetes.
      Outcome measures were medically-attended episodes of infections of the
      respiratory tract, urinary tract, skin and mucous membranes. Multivariate and
      multinomial logistic regression analysis was applied to determine independent
      risks of infections and their recurrence in patients with diabetes compared to
      controls. RESULTS: Upper respiratory-tract infections were as common in diabetes
      patients as in controls. Diabetes patients had a higher risk of lower respiratory
      tract infections (DM2: odds ratio (OR): 1.30; 95% CI: 1.11-1.52), urinary-tract
      infections (DM1: OR: 1.56; 95% CI: 1.13-2.15; DM2: OR: 1.21; 95% CI: 1.07-1.38),
      bacterial skin or mucous-membrane infections (DM1: OR: 1.48; 95% CI: 1.01-2.15;
      DM2: OR: 1.32; 95% CI: 1.13-1.55) and mycotic skin or mucous-membrane infections
      (DM2: OR: 1.41; 95% CI: 1.24-1.61). The risk of recurrence of these common
      infections was seen to be increased. CONCLUSIONS: Patients with type-1 and type-2
      diabetes are at increased risk of lower respiratory-tract infections, urinary
      tract infections and skin or mucous-membrane infections.

PMID- 16566420
TI  - [Trachea compression due to a Kommerell diverticulum in a patient with a right
      sided aorta].
AB  - A 64-year-old man who was evaluated for a long history of a discontinuous barking
      cough with difficulty in coughing up sputum was found to have 90% stenosis of the
      trachea. Further imaging studies revealed a right-sided descending aorta with an
      aberrant left subclavian artery arising from a Kommerell diverticulum. This
      caused the compression of the trachea. The compression was relieved by
      transposition of the aberrant left subclavian artery to the ascending aorta and
      replacement of the aneurysmatic part of the aorta by an endoprosthesis.

PMID- 16566421
TI  - [Colostomy as a cause of deviation colitis in a blind-ended bowel segment].
AB  - Two women aged 63 and 53 who had undergone colostomy for faecal incontinence,
      presented a few months later complaining of anal blood and mucous loss. On
      sigmoidoscopy, a previously healthy section of colorectum seemed to be inflamed.
      Local treatment with hydrocortisone and mesalazine and oral prednisolone did not
      relieve the symptoms. Subsequently the affected part of the colon was resected
      upon which the anal blood and mucous loss stopped. After a deviating stoma
      procedure, the colonic segment diverted from the faecal stream can develop signs
      of non-specific inflammation. The risk of colitis following the creation of a
      stoma is 0-50%. On systematic endoscopy 3-36 months following deviation, the risk
      of findings corresponding to deviation colitis is 50-100%. Symptoms are usually
      mild but can be so devastating that continuity of the faecal stream has to be
      restored or further resection is warranted.

PMID- 16566422
TI  - [Complete atrioventricular block during galantamine therapy].
AB  - A 77-year-old man who for 5 months had been being treated with galantamine for
      early Alzheimer's disease, suddenly became unwell. He was bradycardic and his ECG
      showed a complete atrioventricular block. This was treated by implantation of a
      pacemaker. Treatment with galantamine was continued. A month later he had no
      cardiac symptoms and his dementia score on a cognitive scale had improved.
      Cholinesterase inhibitors may have adverse effects on the heart. Patients
      starting treatment with cholinesterase inhibitors should be screened for an
      increased risk of cardiac arrhythmias by investigating their potassium
      concentrations and running an ECG.

PMID- 16566423
TI  - [Induced abortion in The Netherlands in the twentieth century; from taboo to
      revolutionary change].
AB  - Between 1890 and 1945 the number of induced (criminal) abortions increased in
      Amsterdam; from 1945 up until the 1960s the number decreased slightly. In 1965
      the number of induced abortions that took place in Amsterdam was estimated at
      more than 2000. Complications were frequent and included infections, septicaemia,
      damage caused by injected soap and sometimes air embolism. Women in Amsterdam
      often used primitive methods of contraception, but effective methods, such as
      condoms and diaphragms, were also used to some degree. Oral contraception was
      introduced in The Netherlands in 1962. Its use increased rapidly and consequently
      many doctors were confronted with problems surrounding contraception, including
      failures and abortion requests. After a television programme on abortion in 1967,
      requests for abortion surged. Hospitals set up multidisciplinary abortion
      committees to assess the requests, but soon it became evident that the women
      themselves were better able to judge whether they should undergo the procedure.
      Abortion clinics were established outside hospitals. Support from the feminist
      movement played a role after changes were already underway. The nationwide number
      of abortions increased to 21,000 in 1972 and to about 25,000 in the 1990s. The
      number remained stable, even among teenagers, because caregivers placed a great
      deal of emphasis on adequate contraception.

PMID- 16566424
TI  - [A study of non-antibiotic versus antibiotic prophylaxis for recurrent urinary
      tract infections in women (the NAPRUTI study)].
AB  - Patient enrolment in the 'Non-antibiotic versus antibiotic prophylaxis for
      recurrent urinary-tract infections' (NAPRUTI) study was started in September
      2005. In this study of women with recurrent urinary-tract infections we aim to
      investigate the effect of 12 months of non-antibiotic prophylaxis in comparison
      with antibiotic prophylaxis on the rate of recurrence of urinary-tract infections
      and the development of antibiotic resistance. The study consists of two
      interlinked, randomised, clinical non-inferiority trials. In one trial, 280
      premenopausal women will receive either cranberry capsules (twice daily 500 mg)
      or standardised antibiotic therapy (once daily 480 mg trimethoprim
      sulfamethoxazole). In the other trial, 280 postmenopausal women will receive
      either oral lactobacilli (twice daily a capsule with > 10(9) colony-forming units
      of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14) or standardised
      antibiotic therapy. Non-inferiority of non-antibiotic prophylaxis would be
      attractive given its potential to reduce the prevalence of microbial resistance
      to antibiotics significantly.

PMID- 16566425
TI  - [Lifestyle intervention for the prevention of cardiovascular disease].

PMID- 16566426
TI  - [Lifestyle intervention for the prevention of cardiovascular disease].

PMID- 16566427
TI  - [Corticosteroids and the risk of glaucoma].

PMID- 16566428
TI  - [Measures to reduce absorption in the treatment of intoxications].

PMID- 16566429
TI  - [Gynaecological diagnosis of postmenopausal women with abnormal vaginal bleeding:
      a comparison with the guideline].

PMID- 16566430
TI  - [Gynaecological diagnosis of postmenopausal women with abnormal vaginal bleeding:
      a comparison with the guideline].

PMID- 16566431
TI  - Neuronal input pathways to the brain's biological clock and their functional
      significance.
AB  - Circadian rhythms are entrained daily by environmental photic and non-photic
      cues. The present review describes the anatomy and functional characteristics of
      the three major input pathways to the circadian clock mediating entrainment: the
      retino-hypothalamic tract, the geniculo-hypothalamic tract and the midbrain raphe
      projection.

PMID- 16566432
TI  - Cell substrates: where do we stand after 50 years of discussion?
AB  - The issue of which cells are acceptable as substrates for the production of
      biological products, and especially vaccines, has been with us in one form or
      another since the development of cell cultures in the 1950s. The major cell
      substrate events that occurred over the past 50 years are reviewed briefly,
      including the outcomes of the seven most significant meetings. Cell DNA has been
      discussed for 30 years with incomplete resolution of some aspects of the issue.
      The currently available information on the potential oncogenicity of cellular DNA
      derived from continuous cell lines for which there is no evidence of either viral
      integration or extrachromosomal viral elements is reviewed. Issues associated
      with the continuing regulatory uncertainty about cell DNA are discussed. A
      perspective is provided on the answers to four questions: (i) what do we know now
      about the DNA issue? (ii) what can we conclude from what we know now? (iii) what
      more information, if any, is needed to provide updated guidance? and how do we
      reach a consensus and updated guidance? And finally, a way forward is presented.

PMID- 16566433
TI  - The uptake and fate of exogenous cellular DNA in mammalian cells.
AB  - Mammalian cells take up exogenous DNA very inefficiently. However, in the absence
      of viral vectors, DNA can be transfected into cells by co-precipitation with
      calcium phosphate and usually also with carrier DNA or by lipofection or
      electroporation. Such DNA can be expressed efficiently by cells. Alternatively,
      direct injection can also result in uptake and expression of transgenes. Without
      carefully designed means to target DNA specifically to integrate into the host
      genome, the vast majority of internalised DNA remains extra-chromosomal and is
      degraded. The likely fate of DNA which in low levels may contaminate vaccines
      derived from mammalian cell lines, will also be destruction. There is a
      theoretical risk of DNA integration events with random sequences of donor-derived
      DNA but the probability of that leading to serious adverse effects to the host is
      extremely small.

PMID- 16566434
TI  - Lessons learned from gene therapy concerning and the use of integrating vectors
      and the possible risk of insertional oncogenesis.

PMID- 16566436
TI  - Biological activity of residual cell-substrate DNA.
AB  - Vaccines and other biological products manufactured in cells contain
      contaminating residual DNA derived from that production cell substrate, with the
      amount and form of this DNA depending mainly on the type of vaccine. The
      potential risk of this cellular DNA has been debated for over 40 years without
      resolution. Opinions on residual DNA have varied from it being considered an
      inert contaminant, and thus its presence should not be deemed to be a risk to
      vaccine recipients, to it being considered an important risk factor, particularly
      for vaccines manufactured in certain cell substrates, such as cells derived from
      tumours or cells that are tumorigenic. We are not of the opinion that DNA can be
      considered biologically inert, but whether or what risk residual cell-substrate
      DNA poses remains to be determined. In this paper, we discuss our approaches to
      address this issue and describe some preliminary work.

PMID- 16566435
TI  - Adaptation of the WHO guideline for residual DNA in parenteral vaccines produced
      on continuous cell lines to a limit for oral vaccines.
AB  - Although there is a WHO guidance for a limit on residual DNA for parenterally
      administered vaccines produced on continuous cell lines, there is no
      corresponding guidance for oral vaccines. To help determine an oral limit, we
      performed a study of Vero cell DNA uptake in rats, in which the relative uptake
      and persistence of Vero cell DNA administered orally was compared to its uptake
      when delivered intramuscularly (IM). The results of this study allowed the
      generation of an empirically derived IM versus oral factor (10(6)) representing
      the relative inefficiency of DNA uptake by oral administration. This factor was
      then applied to the WHO recommended parenteral limit of 10 ng/dose to determine a
      corresponding upper limit on the level of residual Vero cell DNA for an oral
      vaccine of 10 mg. As a conservative approach, this empirically determined limit
      was reduced 100-fold to 100 microg. Thus, the results of this animal study,
      together with additional evidence in the literature, support a residual DNA
      safety limit of 100 microg per dose for an oral vaccine produced on a continuous
      cell line.

PMID- 16566438
TI  - Practical assay issues with the PERT/PBRT assay: a highly sensitive reverse
      transcriptase assay.
AB  - Product safety testing for retroviruses can be achieved by a panel of screening
      assays, including electron microscopy, viral gene specific PCRs, virus
      propagation, and detection of reverse transciptase activity. The application of
      PCR-based reverse transcriptase assays (PERT) that are approximately a million
      fold more sensitive than conventional nucleotide incorporation assays in the
      testing of biologicals is described. Use of PERT assays can be applied to three
      areas: (i) screening for adventitious retrovirus contamination; (ii) detecting
      and quantifying endogenous viral particle load and (iii) monitoring levels of
      infectious retrovirus generation in cell lines that contain endogenous
      retroviruses.

PMID- 16566437
TI  - Molecular methods for virus discovery.
AB  - The potential use of novel cell substrates from diverse animal species raises
      concerns about the transmission of hitherto unknown viral agents. Viruses that do
      not cause a cytopathic effect in cell culture may escape detection by
      conventional methods and molecular methods may therefore prove useful for
      screening for hitherto unknown viruses. This review describes currently used
      molecular methods for virus discovery, including degenerate PCR assays,
      representational difference analysis and rolling circle amplification, and
      summarises the advantages and disadvantages of each technique.

PMID- 16566439
TI  - Antibodies to SV40 in sera from humans and macaques.

PMID- 16566441
TI  - Adventitious agent test methods.

PMID- 16566440
TI  - Polio vaccines, SV40 and human tumours, an update on false positive and false
      negative results.
AB  - Simian virus 40 (SV40) has been detected in different human tumours in numerous
      laboratories. The detection of SV40 in human tumours has been linked to the
      administration of SV40-contaminated polio vaccines from 1954 until 1963. Many of
      these reports linked SV40 to human mesothelioma. Some studies have failed to
      detect SV40 in human tumours and this has caused a controversy. Here we review
      the current literature. Moreover, we present evidence showing how differences in
      the sensitivities of methodologies can lead to a very different interpretation of
      the same study. The same 20 mesothelioma specimens all tested negative, 2/20
      tested positive or 7/20 tested positive for SV40 Tag by simply changing the
      detection method on the same immuno-precipitation/western blot membranes. These
      results provide a simple explanation for some of the apparent discordant results
      reported in the literature.

PMID- 16566442
TI  - Scope and practicality of in vivo testing for adventitious agents.
AB  - An overview of the in vivo assays currently performed to test for the presence of
      adventitious contaminants is available. Retrospective validation data have been
      reviewed. Assay problems specifically related to the testing of vaccine viral
      stocks and cell substrates may be discussed.

PMID- 16566443
TI  - Detection of adventitious viruses in biologicals--a rare occurrence.
AB  - Adventitious virus assays are performed as part of raw materials testing, cell
      line characterization, and lot-release testing of biologicals such as monoclonal
      antibodies, gene therapy vectors, recombinant proteins, and vaccines. The testing
      methods follow guidance provided in the 9 CFR (bovine and porcine raw materials
      testing, and certain vaccine products) or Points to Consider documents (cell line
      characterization and evaluation of the majority of biologicals). The
      methodologies used and the types of adventitious viruses detected during testing
      of the various types of samples are discussed in this paper. The detection of
      adventitious viruses is quite rare, especially during evaluation of cell banks
      and biologicals produced in human, mouse, or insect cell substrates. The most
      common detection scenarios include bovine viral diarrhoea virus in foetal bovine
      serum samples, porcine parvovirus in porcine substrates, and murine minute virus,
      REO virus, and Cache Valley virus in Chinese hamster cell-derived bulk harvests.
      The two last-named viral entities are believed to be introduced via bovine serum
      used during the manufacturing process (during scale-up or during the entire
      process). Knowledge of the types of agents being detected is useful in designing
      viral clearance methodologies for purification processes and in engineering
      manufacturing processes and facilities.

PMID- 16566444
TI  - Approaches to the release of a master cell bank of PER.C6 cells; a novel cell
      substrate for the manufacture of human vaccines.
AB  - At Merck and Co. we have developed a recombinant E1 deficient adenovirus type 5
      vaccine vector for HIV-1 and have adopted the PER.C6 cell line as a cell
      substrate for the manufacture of this vector for Phase I and II clinical trials.
      The PER.C6 cell line was developed at Crucell by the transfection of human
      primary embryonic retinoblasts with a transgene of E1 constructed with a minimum
      of E1 coding sequences to preclude homologous recombination generating
      replication-competent adenovirus, between E1 sequences in PER.C6 and adenovirus
      vectors with E1 deletions of the same molecular coordinates. We have developed a
      Master Cell Bank (MCB) of PER.C6 cells under serum-free conditions of suspension
      culture from a vial of PER.C6 cells obtained from Crucell. This MCB has been
      released according to an extensive panel of testing for the detection of
      adventitious viral agents, including assays for sterility and mycoplasma, in vivo
      and in vitro assays for the detection of viruses of human, bovine and porcine
      origin, replication competent adenoviruses, sensitive PERT assays for the
      detection of RT in supernatants of co-cultivations, electron microscopy and a
      panel of PCR-based assays for specific human and animal viruses. This MCB has
      been used for the manufacture of vaccine vector supporting a number of IND
      submissions for Phase I clinical trials over a three-year period during which the
      panel of PCR testing applied to the MCB has been judiciously expanded. Advances
      in QPCR technology, liquid handling systems, and more recently mass spectrometry
      offer the possibility that very broad panels of primers and probes capable of the
      detection of all known human viruses can be applied routinely to support the
      release of biologicals for human clinical trials. The impact of this breadth of
      testing on the continued reliance of classical in vivo and in vitro assays for
      adventitious viruses is clearly an emerging issue worthy of serious debate.

PMID- 16566445
TI  - Newer molecular approaches to detect known viruses and previously unrecognized
      viruses in cell substrates.
AB  - The theme of this brief presentation is that there are tremendous advances not
      only in PCR-based detection but in other novel ways of detecting viruses and
      other agents. Much of the research is now being driven by the bio-defence agenda.
      Somehow those with manufacturing and regulatory responsibilities have to keep
      abreast of these developments and incorporate them as they become available into
      defining the safety of cell substrates. I am concerned that these techniques are
      and may remain academic research tools without validation or standardization, and
      that individual academic laboratories will not develop the capacity and special
      skills necessary to satisfy regulatory requirements, but that there is a
      tremendous research incentive in this area that needs to be linked with the
      development of safe prophylactic and therapeutic biologicals. With that, I will
      finish what I would consider as a report rather than an original talk.

PMID- 16566446
TI  - Basis for sample size in international conference on harmonization guidances.

PMID- 16566447
TI  - Statistical bases for defining level of assurance.
AB  - Assurance of a low risk that material produced in cell culture harbours
      adventitious agents is provided through carefully conducted clearance studies, as
      well as quality control testing. Clearance studies are a form of quality
      assurance, and are used to demonstrate the ability of the manufacturing process
      to minimize or neutralize unwanted contaminants. Quality control testing is
      confirmation of a low risk that manufactured lots are contaminated with an
      adventitious agent. Neither of these can guarantee, however, that product
      released to the customer will be completely free of contaminants. Clearance
      studies provide information on log reduction of a contaminant, but by their
      nature cannot demonstrate complete elimination. In quality control testing, the
      ability to support the claim that there is minimal risk of a lot containing an
      adventitious agent depends on the quantity of material being tested and on the
      sensitivity of the detection assay. Statistical methods can be used both to
      design clearance studies, as well as control tests, to achieve a desirable level
      of assurance that the contaminant is below a defined threshold in the product.
      Basic data analysis methods, such as confidence intervals, improve the quality of
      information, by showing the range of adventitious agent reduction or level.

PMID- 16566449
TI  - Insect cells as a new substrate for vaccine production.
AB  - Vaccine antigens can be expressed in several expression systems, of which
      expression in eukaryotic cell lines is a well-known example. Whereas for most
      current applications cell substrates such as Vero, MRC-5 or chicken embryo
      fibroblasts are used, cell lines derived from insects present an alternative for
      the future production of vaccines. Since such substrates are not yet extensively
      used, knowledge about their feasibility and safety for vaccine antigen production
      is limited. In the current example, an insect-derived cell line Hi-5, used for
      the expression of the human papilloma virus L1 antigen, was extensively
      characterized, in particular for aspects of viral safety. A comprehensive QC
      testing programme, complemented with additional characterization tests relevant
      to the insect nature of the cell line, was developed. Current results indicate
      the satisfactory quality and safety of the Hi-5 cell line. The proposed testing
      programme could stand as an example for the release testing and further
      characterization which would be required for insect cell lines.

PMID- 16566448
TI  - Comprehensive characterization of the 293-ORF6 cell line.

PMID- 16566450
TI  - Safety assessment of Madin Darby canine kidney cells as vaccine substrate.
AB  - Conventional influenza vaccines are manufactured using embryonated chicken eggs,
      a substrate with little flexibility and vulnerable to extraneous agents. Solvay
      Pharmaceuticals developed a production technology based on the continuous cell
      line Madin Darby Canine Kidney (MDCK) as vaccine cell substrate. A risk-based
      safety assessment of MDCK, with respect to tumorigenicity of intact cells and
      oncogenicity of cellular components, cellular DNA and adventitious agents, shows
      that this substrate is as safe as other substrates and therefore without
      increased risk to the vaccine recipient.

PMID- 16566451
TI  - Tumorigenicity assessments of Per.C6 cells and of an Ad5-vectored HIV-1 vaccine
      produced on this continuous cell line.
AB  - PER.C6, a cell line derived from human embryonic retinal cells transformed with
      the Adenovirus Type 5 (Ad5) E1A and E1B genes, is used to produce E1-deleted Ad5
      vectors such as the MRKAd5 HIV-1 gag vaccine. While whole, live PER.C6 cells are
      capable of growing as tumours when transplanted subcutaneously into
      immunodeficient nude mice at a high dosage, the process for vaccine production
      includes filtration steps and other methods which effectively preclude
      contamination by intact viable substrate cells. However, because of the
      neoplastic nature of this cell line, we carried out a series of investigations to
      assess the tumorigenic risk posed by residuals from the cell substrate in a
      vaccine. To address concerns about transmission of oncogenic DNA, we demonstrated
      that purified PER.C6 cellular DNA does not induce tumours in newborn hamsters or
      nude mice. To address concerns about other potential residuals, including
      hypothetical adventitious tumour viruses, we demonstrated that a PER.C6 cell
      lysate and a MRKAd5 HIV-1 gag vaccine produced on PER.C6 cells do not induce
      tumours in newborn hamsters or newborn rats. These results, in conjunction with
      the wide panel of viral safety tests performed on these cells, support the safety
      of the PER.C6 as a cell substrate for vaccine production.

PMID- 16566452
TI  - Bovine serum--regulatory issues.
AB  - For many years users of bovine serum in the manufacture of human and veterinary
      biological medicinal products have relied upon USDA 9CFR to ensure the viral
      safety of their serum. Recently, EU regulators have formalised their position by
      issuing guidelines on the use of bovine serum during manufacture. Additionally,
      the European Pharmacopoeia has drafted a monograph on bovine serum. There is good
      harmonisation among the recommendations and requirements although the EU CHMP
      guideline calls for greater attention to be paid to the potential presence of
      infectious bovine polyoma virus. The EU guidelines also call for various tests to
      assess the effect of BVDV antibodies in the detection of BVDV. However, in
      response to criticisms from serum suppliers and users, the stringency of these
      recommendations is being relaxed. The overall viral safety of bovine serum should
      be subject to a risk analysis as infectious virus will invariably be present in
      some batches of serum but remain undetected. Other factors such as the
      geographical source of the serum, the efficacy of viral inactivation/removal
      steps and the ability of specific viruses to grow in the production cells being
      used, should be taken into consideration.

PMID- 16566453
TI  - Vaccine cell substrates: bovine and porcine virus considerations.
AB  - The use of materials of animal origin to supplement cell cultures used in vaccine
      production, viral diagnostic testing, or materials testing may lead to
      contamination of the vaccines, with seroconversion or disease in the vaccinated
      animals, and possible misdiagnosis of diagnostic samples or incorrect test
      results. The methods used by the Center for Veterinary Biologics to monitor serum
      and cell cultures are described. Considerations for the use of animal origin
      materials, especially bovine and porcine, as substrates or additives, plus the
      possibility of crossovers to humans are discussed.

PMID- 16566454
TI  - Animal-free culture process for manufacture of viral vaccines: process validation
      and regulatory perspectives.

PMID- 16566455
TI  - Diagnostics for TSE agents.
AB  - Bovine Spongiform Encephalopathy (BSE) is a fatal acquired neuro-degenerative
      disease in cattle, belonging to the group of transmissible spongiform
      encephalopathies (TSEs) or prion diseases. Since its first recognition in the
      U.K. in 1986, BSE has raised great public health concerns because the BSE agent
      has been shown to cause variant Creutzfeldt Jakob Disease (vCJD) in humans. With
      the introduction of mandatory active surveillance programmes in the European
      Union the need to develop rapid tests to diagnose BSE has become a high priority.
      Up to now, the European Union has approved twelve rapid tests for BSE monitoring
      in cattle, and approval for two new tests which have been evaluated in 2004 is
      pending. These rapid screening tests have been used in active surveillance of BSE
      and have greatly improved the detection of infected cattle before their entry
      into the human food chain. At present, no diagnostic test exists for the
      detection of prions in live animals or humans. New diagnostic techniques aimed at
      increasing the sensitivity and specificity of PrPsc detection in body fluids and
      at identifying novel surrogate markers are under development.

PMID- 16566456
TI  - Production cell substrates and vCJD.

PMID- 16566457
TI  - TSE risk assessment for starting materials used during, or in the manufacture of
      vaccines for human use--a consultant's view of the commercial approach.
AB  - Vaccination is an essential tool to protect humans from many infectious diseases.
      Materials derived from bovine tissues are used in, or during the manufacture of,
      most vaccines. Following the occurrence of BSE in cattle in three continents
      since 1986, the need to ensure the TSE safety of vaccines is vital. Various
      actions have been taken to ensure safety targets are reached. This paper shows
      that selecting starting tissues used in vaccine manufacture on the basis of their
      inherent TSE risk is of prime importance and is more secure than using geography
      as the primary criterion of a safe origin. Other approaches can also contribute
      to safety assurance. These include avoiding, where possible, tissues from
      animals, risk tissues and tissues of unknown or uncertain provenance. It is
      essential to ensure tissues are collected and processed appropriately and
      detailed records are kept. The risk assessment approach, based on the main safety
      factors of Source, Process and Use, coupled with these additional features,
      combine to establish that the TSE safety of vaccines is ensured, despite the
      challenge resulting from the occurrence of BSE.

PMID- 16566458
TI  - A node pruning algorithm based on a Fourier amplitude sensitivity test method.
AB  - In this paper, we propose a new pruning algorithm to obtain the optimal number of
      hidden units of a single layer of a fully connected neural network (NN). The
      technique relies on a global sensitivity analysis of model output. The relevance
      of the hidden nodes is determined by analysing the Fourier decomposition of the
      variance of the model output. Each hidden unit is assigned a ratio (the fraction
      of variance which the unit accounts for) that gives their ranking. This
      quantitative information therefore leads to a suggestion of the most favorable
      units to eliminate. Experimental results suggest that the method can be seen as
      an effective tool available to the user in controlling the complexity in NNs.

PMID- 16566459
TI  - Generalizing self-organizing map for categorical data.
AB  - The self-organizing map (SOM) is an unsupervised neural network which projects
      high-dimensional data onto a low-dimensional grid and visually reveals the
      topological order of the original data. Self-organizing maps have been
      successfully applied to many fields, including engineering and business domains.
      However, the conventional SOM training algorithm handles only numeric data.
      Categorical data are usually converted to a set of binary data before training of
      an SOM takes place. If a simple transformation scheme is adopted, the similarity
      information embedded between categorical values may be lost. Consequently, the
      trained SOM is unable to reflect the correct topological order. This paper
      proposes a generalized self-organizing map model that offers an intuitive method
      of specifying the similarity between categorical values via distance hierarchies
      and, hence, enables the direct process of categorical values during training. In
      fact, distance hierarchy unifies the distance computation of both numeric and
      categorical values. The unification is done by mapping the values to distance
      hierarchies and then measuring the distance in the hierarchies. Experiments on
      synthetic and real datasets were conducted, and the results demonstrated the
      effectiveness of the generalized SOM model.

PMID- 16566460
TI  - The parameterless self-organizing map algorithm.
AB  - The parameterless self-organizing map (PLSOM) is a new neural network algorithm
      based on the self-organizing map (SOM). It eliminates the need for a learning
      rate and annealing schemes for learning rate and neighborhood size. We discuss
      the relative performance of the PLSOM and the SOM and demonstrate some tasks in
      which the SOM fails but the PLSOM performs satisfactory. Finally we discuss some
      example applications of the PLSOM and present a proof of ordering under certain
      limited conditions.

PMID- 16566461
TI  - Implementing online natural gradient learning: problems and solutions.
AB  - The online natural gradient learning is an efficient algorithm to resolve the
      slow learning speed and poor performance of the standard gradient descent method.
      However, there are several problems to implement this algorithm. In this paper,
      we proposed a new algorithm to solve these problems and then compared the new
      algorithm with other known algorithms for online learning, including Almeida
      Langlois-Amaral-Plakhov algorithm (ALAP), Vario-eta, local adaptive learning rate
      and learning with momentum etc., using sample data sets from Proben1 and
      normalized handwritten digits, automatically scanned from envelopes by the U.S.
      Postal Services. The strong and weak points of these algorithms were analyzed and
      tested empirically. We found out that using the online training error as the
      criterion to determine whether the learning rate should be changed or not is not
      appropriate and our new algorithm has better performance than other existing
      online algorithms.

PMID- 16566462
TI  - The linear separability problem: some testing methods.
AB  - The notion of linear separability is used widely in machine learning research.
      Learning algorithms that use this concept to learn include neural networks
      (single layer perceptron and recursive deterministic perceptron), and kernel
      machines (support vector machines). This paper presents an overview of several of
      the methods for testing linear separability between two classes. The methods are
      divided into four groups: Those based on linear programming, those based on
      computational geometry, one based on neural networks, and one based on quadratic
      programming. The Fisher linear discriminant method is also presented. A section
      on the quantification of the complexity of classification problems is included.

PMID- 16566463
TI  - Modulated Hebb-Oja learning rule--a method for principal subspace analysis.
AB  - This paper presents analysis of the recently proposed modulated Hebb-Oja (MHO)
      method that performs linear mapping to a lower-dimensional subspace. Principal
      component subspace is the method that will be analyzed. Comparing to some other
      well-known methods for yielding principal component subspace (e.g., Oja's
      Subspace Learning Algorithm), the proposed method has one feature that could be
      seen as desirable from the biological point of view--synaptic efficacy learning
      rule does not need the explicit information about the value of the other
      efficacies to make individual efficacy modification. Also, the simplicity of the
      "neural circuits" that perform global computations and a fact that their number
      does not depend on the number of input and output neurons, could be seen as good
      features of the proposed method.

PMID- 16566464
TI  - Toward the training of feed-forward neural networks with the D-optimum input
      sequence.
AB  - The problem under consideration is to obtain a measurement schedule for training
      neural networks. This task is perceived as an experimental design in a given
      design space that is obtained in such a way as to minimize the difference between
      the neural network and the system being considered. This difference can be
      expressed in many different ways and one of them, namely, the D-optimality
      criterion is used in this paper. In particular, the paper presents a unified and
      comprehensive treatment of this problem by discussing the existing and previously
      unpublished properties of the optimum experimental design (OED) for neural
      networks. The consequences of the above properties are discussed as well. A
      hybrid algorithm that can be used for both the training and data development of
      neural networks is another important contribution of this paper. A careful
      analysis of the algorithm is presented and its comprehensive convergence analysis
      with the help of the Lyapunov method are given. The paper contains a number of
      numerical examples that justify the application of the OED theory for neural
      networks. Moreover, an industrial application example is given that deals with
      the valve actuator.

PMID- 16566465
TI  - Orthogonal search-based rule extraction (OSRE) for trained neural networks: a
      practical and efficient approach.
AB  - There is much interest in rule extraction from neural networks and a plethora of
      different methods have been proposed for this purpose. We discuss the merits of
      pedagogical and decompositional approaches to rule extraction from trained neural
      networks, and show that some currently used methods for binary data comply with a
      theoretical formalism for extraction of Boolean rules from continuously valued
      logic. This formalism is extended into a generic methodology for rule extraction
      from smooth decision surfaces fitted to discrete or quantized continuous
      variables independently of the analytical structure of the underlying model, and
      in a manner that is efficient even for high input dimensions. This methodology is
      then tested with Monks' data, for which exact rules are obtained and to
      Wisconsin's breast cancer data, where a small number of high-order rules are
      identified whose discriminatory performance can be directly visualized.

PMID- 16566466
TI  - A bidirectional heteroassociative memory for binary and grey-level patterns.
AB  - Typical bidirectional associative memories (BAM) use an offline, one-shot
      learning rule, have poor memory storage capacity, are sensitive to noise, and are
      subject to spurious steady states during recall. Recent work on BAM has improved
      network performance in relation to noisy recall and the number of spurious
      attractors, but at the cost of an increase in BAM complexity. In all cases, the
      networks can only recall bipolar stimuli and, thus, are of limited use for grey
      level pattern recall. In this paper, we introduce a new bidirectional
      heteroassociative memory model that uses a simple self-convergent iterative
      learning rule and a new nonlinear output function. As a result, the model can
      learn online without being subject to overlearning. Our simulation results show
      that this new model causes fewer spurious attractors when compared to others
      popular BAM networks, for a comparable performance in terms of tolerance to noise
      and storage capacity. In addition, the novel output function enables it to learn
      and recall grey-level patterns in a bidirectional way.

PMID- 16566467
TI  - Basins of attraction in fully asynchronous discrete-time discrete-state dynamic
      networks.
AB  - This paper gives a formulation of the basins of fixed point states of fully
      asynchronous discrete-time discrete-state dynamic networks. That formulation
      provides two advantages. The first one is to point out the different behaviors
      between synchronous and asynchronous modes and the second one is to allow us to
      easily deduce an algorithm which determines the behavior of a network for a given
      initialization. In the context of this study, we consider networks of a large
      number of neurons (or units, processors, etc.), whose dynamic is fully
      asynchronous with overlapping updates. We suppose that the neurons take a finite
      number of discrete states and that the updating scheme is discrete in time. We
      make no hypothesis on the activation functions of the nodes, so that the dynamic
      of the network may have multiple cycles and/or basins. Our results are
      illustrated on a simple example of a fully asynchronous Hopfield neural network.

PMID- 16566468
TI  - Dynamics analysis and analog associative memory of networks with LT neurons.
AB  - The additive recurrent network structure of linear threshold neurons represents a
      class of biologically-motivated models, where nonsaturating transfer functions
      are necessary for representing neuronal activities, such as that of cortical
      neurons. This paper extends the existing results of dynamics analysis of such
      linear threshold networks by establishing new and milder conditions for
      boundedness and asymptotical stability, while allowing for multistability. As a
      condition for asymptotical stability, it is found that boundedness does not
      require a deterministic matrix to be symmetric or possess positive off-diagonal
      entries. The conditions put forward an explicit way to design and analyze such
      networks. Based on the established theory, an alternate approach to study such
      networks is through permitted and forbidden sets. An application of the linear
      threshold (LT) network is analog associative memory, for which a simple design
      method describing the associative memory is suggested in this paper. The proposed
      design method is similar to a generalized Hebbian approach, but with distinctions
      of additional network parameters for normalization, excitation and inhibition,
      both on a global and local scale. The computational abilities of the network are
      dependent on its nonlinear dynamics, which in turn is reliant upon the sparsity
      of the memory vectors.

PMID- 16566469
TI  - Blind estimation of channel parameters and source components for EEG signals: a
      sparse factorization approach.
AB  - In this paper, we use a two-stage sparse factorization approach for blindly
      estimating the channel parameters and then estimating source components for
      electroencephalogram (EEG) signals. EEG signals are assumed to be linear mixtures
      of source components, artifacts, etc. Therefore, a raw EEG data matrix can be
      factored into the product of two matrices, one of which represents the mixing
      matrix and the other the source component matrix. Furthermore, the components are
      sparse in the time-frequency domain, i.e., the factorization is a sparse
      factorization in the time frequency domain. It is a challenging task to estimate
      the mixing matrix. Our extensive analysis and computational results, which were
      based on many sets of EEG data, not only provide firm evidences supporting the
      above assumption, but also prompt us to propose a new algorithm for estimating
      the mixing matrix. After the mixing matrix is estimated, the source components
      are estimated in the time frequency domain using a linear programming method. In
      an example of the potential applications of our approach, we analyzed the EEG
      data that was obtained from a modified Sternberg memory experiment. Two almost
      uncorrelated components obtained by applying the sparse factorization method were
      selected for phase synchronization analysis. Several interesting findings were
      obtained, especially that memory-related synchronization and desynchronization
      appear in the alpha band, and that the strength of alpha band synchronization is
      related to memory performance.

PMID- 16566470
TI  - Adaptive wavelet neural network control with hysteresis estimation for piezo
      positioning mechanism.
AB  - An adaptive wavelet neural network (AWNN) control with hysteresis estimation is
      proposed in this study to improve the control performance of a piezo-positioning
      mechanism, which is always severely deteriorated due to hysteresis effect. First,
      the control system configuration of the piezo-positioning mechanism is
      introduced. Then, a new hysteretic model by integrating a modified hysteresis
      friction force function is proposed to represent the dynamics of the overall
      piezo-positioning mechanism. According to this developed dynamics, an AWNN
      controller with hysteresis estimation is proposed. In the proposed AWNN
      controller, a wavelet neural network (WNN) with accurate approximation capability
      is employed to approximate the part of the unknown function in the proposed
      dynamics of the piezo-positioning mechanism, and a robust compensator is proposed
      to confront the lumped uncertainty that comprises the inevitable approximation
      errors due to finite number of wavelet basis functions and disturbances, optimal
      parameter vectors, and higher order terms in Taylor series. Moreover, adaptive
      learning algorithms for the online learning of the parameters of the WNN are
      derived based on the Lyapunov stability theorem. Finally, the command tracking
      performance and the robustness to external load disturbance of the proposed AWNN
      control system are illustrated by some experimental results.

PMID- 16566471
TI  - Modeling and inverse controller design for an unmanned aerial vehicle based on
      the self-organizing map.
AB  - The next generation of aircraft will have dynamics that vary considerably over
      the operating regime. A single controller will have difficulty to meet the design
      specifications. In this paper, a self-organizing map (SOM)-based local linear
      modeling scheme of an unmanned aerial vehicle (UAV) is developed to design a set
      of inverse controllers. The SOM selects the operating regime depending only on
      the embedded output space information and avoids normalization of the input data.
      Each local linear model is associated with a linear controller, which is easy to
      design. Switching of the controllers is done synchronously with the active local
      linear model that tracks the different operating conditions. The proposed
      multiple modeling and control strategy has been successfully tested in a
      simulator that models the LoFLYTE UAV.

PMID- 16566472
TI  - Neural-network-based adaptive UPFC for improving transient stability performance
      of power system.
AB  - This paper uses the recently proposed H(infinity)-learning method, for updating
      the parameter of the radial basis function neural network (RBFNN) used as a
      control scheme for the unified power flow controller (UPFC) to improve the
      transient stability performance of a multimachine power system. The RBFNN uses a
      single neuron architecture whose input is proportional to the difference in error
      and the updating of its parameters is carried via a proportional value of the
      error. Also, the coefficients of the difference of error, error, and auxiliary
      signal used for improving damping performance are depicted by a genetic
      algorithm. The performance of the newly designed controller is evaluated in a
      four-machine power system subjected to different types of disturbances. The newly
      designed single-neuron RBFNN-based UPFC exhibits better damping performance
      compared to the conventional PID as well as the extended Kalman filter (EKF)
      updating-based RBFNN scheme, making the unstable cases stable. Its simple
      architecture reduces the computational burden, thereby making it attractive for
      real-time implementation. Also, all the machines are being equipped with the
      conventional power system stabilizer (PSS) to study the coordinated effect of
      UPFC and PSS in the system.

PMID- 16566473
TI  - Sparse Bayesian kernel survival analysis for modeling the growth domain of
      microbial pathogens.
AB  - Survival analysis is a branch of statistics concerned with the time elapsing
      before "failure," with diverse applications in medical statistics and the
      analysis of the reliability of electrical or mechanical components. We introduce
      a parametric accelerated life survival analysis model based on kernel learning
      methods that, at least in principal, is able to learn arbitrary dependencies
      between a vector of explanatory variables and the scale of the distribution of
      survival times. The proposed kernel survival analysis method is then used to
      model the growth domain of Clostridium botulinum, the food processing and storage
      conditions permitting the growth of this foodborne microbial pathogen, leading to
      the production of the neurotoxin responsible for botulism. A Bayesian training
      procedure, based on the evidence framework, is used for model selection and to
      provide a credible interval on model predictions. The kernel survival analysis
      models are found to be more accurate than models based on more traditional
      survival analysis techniques but also suggest a risk assessment of the foodborne
      botulism hazard would benefit from the collection of additional data.

PMID- 16566475
TI  - Neuromorphic walking gait control.
AB  - We present a neuromorphic pattern generator for controlling the walking gaits of
      four-legged robots which is inspired by central pattern generators found in the
      nervous system and which is implemented as a very large scale integrated (VLSI)
      chip. The chip contains oscillator circuits that mimic the output of motor
      neurons in a strongly simplified way. We show that four coupled oscillators can
      produce rhythmic patterns with phase relationships that are appropriate to
      generate all four-legged animal walking gaits. These phase relationships together
      with frequency and duty cycle of the oscillators determine the walking behavior
      of a robot driven by the chip, and they depend on a small set of stationary bias
      voltages. We give analytic expressions for these dependencies. This chip reduces
      the complex, dynamic inter-leg control problem associated with walking gait
      generation to the problem of setting a few stationary parameters. It provides a
      compact and low power solution for walking gait control in robots.

PMID- 16566474
TI  - A neuromorphic depth-from-motion vision model with STDP adaptation.
AB  - We propose a simplified depth-from-motion vision model based on leaky integrate
      and-fire (LIF) neurons for edge detection and two-dimensional depth recovery. In
      the model, every LIF neuron is able to detect the irradiance edges passing
      through its receptive field in an optical flow field, and respond to the
      detection by firing a spike when the neuron's firing criterion is satisfied. If a
      neuron fires a spike, the time-of-travel of the spike-associated edge is
      transferred as the prediction information to the next synapse-linked neuron to
      determine its state. Correlations between input spikes and their timing thus
      encode depth in the visual field. The adaptation of synapses mediated by spike
      timing-dependent plasticity is used to improve the algorithm's robustness against
      inaccuracy caused by spurious edge propagation. The algorithm is characterized on
      both artificial and real image sequences. The implementation of the algorithm in
      analog very large scale integrated (aVLSI) circuitry is also discussed.

PMID- 16566476
TI  - Adaptive neural network control for a class of low-triangular-structured
      nonlinear systems.
AB  - In this paper, a class of unknown perturbed nonlinear systems is theoretically
      stabilized by using adaptive neural network control. The systems, with
      disturbances and nonaffine unknown functions, have low triangular structure,
      which generalizes both strict-feedback uncertain systems and pure-feedback ones.
      There do not exist any effective methods to stabilize this kind of systems. With
      some new conclusions for Nussbaum-Gain functions (NGF) and the idea of
      backstepping, semiglobal, uniformal, and ultimate boundedness of all the signals
      in the closed-loop is proved at equilibrium point. The two problems, control
      directions and control singularity, are well dealt with. The effectiveness of
      proposed scheme is shown by simulation on a proper nonlinear system.

PMID- 16566477
TI  - Computation of Adalines' sensitivity to weight perturbation.
AB  - In this paper, the sensitivity of Adalines to weight perturbation is discussed.
      According to the discrete feature of Adalines' input and output, the sensitivity
      is defined as the probability of an Adaline's erroneous outputs due to weight
      perturbation with respect to all possible inputs. By means of hypercube model and
      analytical geometry method, a heuristic algorithm is given to accurately compute
      the sensitivity. The accuracy of the algorithm is verified by computer
      simulations.

PMID- 16566478
TI  - Associative memory design for 256 gray-level images using a multilayer neural
      network.
AB  - A design procedure is presented for neural associative memories storing gray
      scale images. It is an evolution of a previous work based on the decomposition of
      the image with 2L gray levels into L binary patterns, stored in L uncoupled
      neural networks. In this letter, an L-layer neural network is proposed with both
      intralayer and interlayer connections. The connections between different layers
      introduce interactions among all the neurons, increasing the recall performance
      with respect to the uncoupled case. In particular, the proposed network can store
      images with the commonly used number of 256 gray levels instead of 16, as in the
      previous approach.

PMID- 16566479
TI  - Convergence of gradient method with momentum for two-layer feedforward neural
      networks.
AB  - A gradient method with momentum for two-layer feedforward neural networks is
      considered. The learning rate is set to be a constant and the momentum factor an
      adaptive variable. Both the weak and strong convergence results are proved, as
      well as the convergence rates for the error function and for the weight. Compared
      to the existing convergence results, our results are more general since we do not
      require the error function to be quadratic.

PMID- 16566480
TI  - On the new method for the control of discrete nonlinear dynamic systems using
      neural networks.
AB  - This correspondence points out an incorrect statement in Adetona et al, 2000, and
      Adetona et al., 2004, about the application of the proposed control law to
      nonminimum phase systems. A counterexample shows the limitations of the control
      law and, furthermore, its control capability to nonminimum phase systems is
      explained.

PMID- 16566481
TI  - Batch map extensions of the kernel-based maximum entropy learning rule.
AB  - In this letter, two batch-map extensions are described for the kernel-based
      maximum entropy learning rule (kMER). In the first, the weights are iteratively
      set to weighted component-wise medians, while in the second the generalized
      median is used, enabling kMER to process symbolic data. Simulations are performed
      to illustrate the extensions.

PMID- 16566482
TI  - Comments on "the 1993 DIMACS graph coloring challenge" and "energy function-based
      approaches to graph coloring".
AB  - Since all graphs in the 1993 DIMACS graph coloring challenge are undirected, each
      edge should be only counted once. However, in some files each edge is counted
      once, whereas in others each edge is counted twice; so a systematical check on
      the DIMACS challenge is made to eliminate the inconsistencies. Besides, the
      experimental results of a previous paper by Blas et al. counted each violated
      edges twice and neglected the inconsistencies in the DIMACS challenge. So the
      correct experimental results of a previous paper by Blas et al are also given.

PMID- 16566483
TI  - Dollar 6,280 and counting.

PMID- 16566484
TI  - Congressional direction on health IT still not clear.

PMID- 16566485
TI  - Busy year ahead in the states.

PMID- 16566487
TI  - Weighing in on obesity.

PMID- 16566486
TI  - Preparing for pandemic: Health plans partner with federal agencies to address the
      threat of avian flu.

PMID- 16566488
TI  - The ABCs of PPOs.

PMID- 16566489
TI  - Immunization practices and policies: a survey of health insurance plans.

PMID- 16566490
TI  - Accreditation: Quality control in an evolving marketplace. Interview by Ed
      Rabinowitz.

PMID- 16566491
TI  - Simplified credentialing works for providers, plans: collaborative technology
      initiative transforms a cumbersome process.

PMID- 16566492
TI  - Principles for improving enterprise agility: Modernizing health IT systems with
      less business risk and disruption.

PMID- 16566493
TI  - Technology-driven care coordination: using health IT to support provider pay-for
      performance.

PMID- 16566494
TI  - The HCA forum. Interview by G Ross Baker.

PMID- 16566495
TI  - A student-written, faculty-reviewed, free, on-line textbook of public health
      management and policy.
AB  - A student-written, faculty-reviewed, on-line textbook of public health management
      and policy has been created in conjunction with a course on this subject. Writing
      a chapter is a requirement for course credit. With each class, each year, this
      textbook is revised and in 2005 is in its sixth edition. This book is in the
      public domain and can be copied and used by others without permission and for
      free.

PMID- 16566496
TI  - Teaching organization theory for healthcare management: three applied learning
      methods.
AB  - Organization theory (OT) provides a way of seeing, describing, analyzing,
      understanding, and improving organizations based on patterns of organizational
      design and behavior (Daft 2004). It gives managers models, principles, and
      methods with which to diagnose and fix organization structure, design, and
      process problems. Health care organizations (HCOs) face serious problems such as
      fatal medical errors, harmful treatment delays, misuse of scarce nurses, costly
      inefficiency, and service failures. Some of health care managers' most critical
      work involves designing and structuring their organizations so their missions,
      visions, and goals can be achieved-and in some cases so their organizations can
      survive. Thus, it is imperative that graduate healthcare management programs
      develop effective approaches for teaching OT to students who will manage HCOs.
      Guided by principles of education, three applied teaching/learning
      activities/assignments were created to teach OT in a graduate healthcare
      management program. These educationalmethods develop students' competency with OT
      applied to HCOs. The teaching techniques in this article may be useful to faculty
      teaching graduate courses in organization theory and related subjects such as
      leadership, quality, and operation management.

PMID- 16566497
TI  - Preceptor and employer evaluation of health administration student competencies.
AB  - A survey tool was designed to ascertain preceptors' and employers' perceptions of
      students after completion of one-year residencies/fellowships or other
      employment. Five-year results from two graduate MHA programs that administer the
      survey are described, along with ways the results have been used in program
      administration. Interpersonal communication skills and working in teams were
      ranked first and second as the most important skills by employers and preceptors
      of both programs. Findings generally show a high level of satisfaction with
      health administration graduates. It is recommended that programs adopt similar
      tools to better attune health administration curricula to marketplace demands.

PMID- 16566498
TI  - The identification of best practices in teaching quality competencies for
      preparing future healthcare leaders.
AB  - The mandate for quality in all aspects of clinical practice, service delivery,
      and management practice has never been greater. The Institute of Medicine's (IOM)
      landmarkwork To Erris Human heightened the urgency of this serious issue. In a
      follow-up report, the IOM's Crossing the Quality Chasm called for radical change
      to achieve numerous quality objectives throughout the continuum of the healthcare
      system including the preparation of future healthcare leaders. This study was
      conducted to assess how effectively healthcare management education faculty are
      meeting the challenge of integrating quality improvement into their curricula and
      how faculty perceived their quality expertise. Another goal was to identify the
      student learning assessment strategies, teaching methods, content, and resources
      utilized by faculty to achieve this integration and to suggest a framework for
      "best practices" in teaching qualitycompetencies citing the literature. The
      study's findings raise a number of important issues with respect to the ways in
      which QI is conceptualized and integrated into curricula and concludes that there
      is substantial need for 'quality improvement' in healthcare management education
      faculty's approaches to the teaching of QI.

PMID- 16566499
TI  - View from the top: CEO perspectives on executive development and succession
      planning practices in healthcare organizations.
AB  - Many healthcare professionals question whether the industry's hospitals and multi
      site systems are implementing the necessary executive development and succession
      planning systems to ensure that high potential managers are prepared and aptly
      selected to assume key executive roles. Survey data, case studies, and cross
      industry comparisons suggest that healthcare organizations may face a leadership
      crisis as the current generation of chief executive officers (CEOs) nears
      retirement while traditional means of developing the leadership pipeline,
      including middle-management positions and graduate programs requiring formal
      residencies, continue to dissipate. Given the daunting challenges that accompany
      the healthcare industry's quest to identify, develop, and retain leadership
      talent, this article provides best practice findings from a qualitative study of
      13 healthcare organizations with a record of exemplary executive development and
      succession planning practices. CEOs from six single-site hospitals, six
      healthcare systems, and one medical group were interviewed to identify industry
      best practices so that healthcare practitioners and educators may utilize the
      findings to enhance the industry's leadership capacity.

PMID- 16566500
TI  - Metric learning for text documents.
AB  - Many algorithms in machine learning rely on being given a good distance metric
      over the input space. Rather than using a default metric such as the Euclidean
      metric, it is desirable to obtain a metric based on the provided data. We
      consider the problem of learning a Riemannian metric associated with a given
      differentiable manifold and a set of points. Our approach to the problem involves
      choosing a metric from a parametric family that is based on maximizing the
      inverse volume of a given data set of points. From a statistical perspective, it
      is related to maximum likelihood under a model that assigns probabilities
      inversely proportional to the Riemannian volume element. We discuss in detail
      learning a metric on the multinomial simplex where the metric candidates are pull
      back metrics of the Fisher information under a Lie group of transformations. When
      applied to text document classification the resulting geodesic distance resemble,
      but outperform, the tfidf cosine similarity measure.

PMID- 16566501
TI  - Graph partitioning active contours (GPAC) for image segmentation.
AB  - In this paper, we introduce new types of variational segmentation cost functions
      and associated active contour methods that are based on pairwise similarities or
      dissimilarities of the pixels. As a solution to a minimization problem, we
      introduce a new curve evolution framework, the graph partitioning active contours
      (GPAC). Using global features, our curve evolution is able to produce results
      close to the ideal minimization of such cost functions. New and efficient
      implementation techniques are also introduced in this paper. Our experiments show
      that GPAC solution is effective on natural images and computationally efficient.
      Experiments on gray-scale, color, and texture images show promising segmentation
      results.

PMID- 16566502
TI  - Variational Bayes for continuous hidden Markov models and its application to
      active learning.
AB  - In this paper, we present a varitional Bayes (VB) framework for learning
      continuous hidden Markov models (CHMMs), and we examine the VB framework within
      active learning. Unlike a maximum likelihood or maximum a posteriori training
      procedure, which yield a point estimate of the CHMM parameters, VB-based training
      yields an estimate of the full posterior of the model parameters. This is
      particularly important for small training sets since it gives a measure of
      confidence in the accuracy of the learned model. This is utilized within the
      context of active learning, for which we acquire labels for those feature vectors
      for which knowledge of the associated label would be most informative for
      reducing model-parameter uncertainty. Three active learning algorithms are
      considered in this paper: 1) query by committee (QBC), with the goal of selecting
      data for labeling that minimize the classification variance, 2) a maximum
      expected information gain method that seeks to label data with the goal of
      reducing the entropy of the model parameters, and 3) an error-reduction-based
      procedure that attempts to minimize classification error over the test data. The
      experimental results are presented for synthetic and measured data. We
      demonstrate that all of these active learning methods can significantly reduce
      the amount of required labeling, compared to random selection of samples for
      labeling.

PMID- 16566503
TI  - A genetic algorithm using hyper-quadtrees for low-dimensional K-means clustering.
AB  - The k-means algorithm is widely used for clustering because of its computational
      efficiency. Given n points in d-dimensional space and the number of desired
      clusters k, k-means seeks a set of k cluster centers so as to minimize the sum of
      the squared Euclidean distance between each point and its nearest cluster center.
      However, the algorithm is very sensitive to the initial selection of centers and
      is likely to converge to partitions that are significantly inferior to the global
      optimum. We present a genetic algorithm (GA) for evolving centers in the k-means
      algorithm that simultaneously identifies good partitions for a range of values
      around a specified k. The set of centers is represented using a hyper-quadtree
      constructed on the data. This representation is exploited in our GA to generate
      an initial population of good centers and to support a novel crossover operation
      that selectively passes good subsets of neighboring centers from parents to
      offspring by swapping subtrees. Experimental results indicate that our GA finds
      the global optimum for data sets with known optima and finds good solutions for
      large simulated data sets.

PMID- 16566504
TI  - Selection of generative models in classification.
AB  - This paper is concerned with the selection of a generative model for supervised
      classification. Classical criteria for model selection assess the fit of a model
      rather than its ability to produce a low classification error rate. A new
      criterion, the Bayesian Entropy Criterion (BEC), is proposed. This criterion
      takes into account the decisional purpose of a model by minimizing the integrated
      classification entropy. It provides an interesting alternative to the cross
      validated error rate which is computationally expensive. The asymptotic behavior
      of the BEC criterion is presented. Numerical experiments on both simulated and
      real data sets show that BEC performs better than the BIC criterion to select a
      model minimizing the classification error rate and provides analogous performance
      to the cross-validated error rate.

PMID- 16566505
TI  - Sparse representation for coarse and fine object recognition.
AB  - This paper offers a sparse, multiscale representation of objects. It captures the
      object appearance by selection from a very large dictionary of Gaussian
      differential basis functions. The learning procedure results from the matching
      pursuit algorithm, while the recognition is based on polynomial approximation to
      the bases, turning image matching into a problem of polynomial evaluation. The
      method is suited for coarse recognition between objects and, by adding more
      bases, also for fine recognition of the object pose. The advantages over the
      common representation using PCA include storing sampled points for recognition is
      not required, adding new objects to an existing data set is trivial because
      retraining other object models is not needed, and significantly in the important
      case where one has to scan an image over multiple locations in search for an
      object, the new representation is readily available as opposed to PCA projection
      at each location. The experimental result on the COIL-100 data set demonstrates
      high recognition accuracy with real-time performance.

PMID- 16566506
TI  - Shapeme histogram projection and matching for partial object recognition.
AB  - Histograms of shape signature or prototypical shapes, called shapemes, have been
      used effectively in previous work for 2D/3D shape matching and recognition. We
      extend the idea of shapeme histogram to recognize partially observed query
      objects from a database of complete model objects. We propose representing each
      model object as a collection of shapeme histograms and match the query histogram
      to this representation in two steps: 1) compute a constrained projection of the
      query histogram onto the subspace spanned by all the shapeme histograms of the
      model and 2) compute a match measure between the query histogram and the
      projection. The first step is formulated as a constrained optimization problem
      that is solved by a sampling algorithm. The second step is formulated under a
      Bayesian framework, where an implicit feature selection process is conducted to
      improve the discrimination capability of shapeme histograms. Results of matching
      partially viewed range objects with a 243 model database demonstrate better
      performance than the original shapeme histogram matching algorithm and other
      approaches.

PMID- 16566507
TI  - A discriminative learning framework with pairwise constraints for video object
      classification.
AB  - To deal with the problem of insufficient labeled data in video object
      classification, one solution is to utilize additional pairwise constraints that
      indicate the relationship between two examples, i.e., whether these examples
      belong to the same class or not. In this paper, we propose a discriminative
      learning approach which can incorporate pairwise constraints into a conventional
      margin-based learning framework. Different from previous work that usually
      attempts to learn better distance metrics or estimate the underlying data
      distribution, the proposed approach can directly model the decision boundary and,
      thus, require fewer model assumptions. Moreover, the proposed approach can handle
      both labeled data and pairwise constraints in a unified framework. In this work,
      we investigate two families of pairwise loss functions, namely, convex and
      nonconvex pairwise loss functions, and then derive three pairwise learning
      algorithms by plugging in the hinge loss and the logistic loss functions. The
      proposed learning algorithms were evaluated using a people identification task on
      two surveillance video data sets. The experiments demonstrated that the proposed
      pairwise learning algorithms considerably outperform the baseline classifiers
      using only labeled data and two other pairwise learning algorithms with the same
      amount of pairwise constraints.

PMID- 16566508
TI  - One-shot learning of object categories.
AB  - Learning visual models of object categories notoriously requires hundreds or
      thousands of training examples. We show that it is possible to learn much
      information about a category from just one, or a handful, of images. The key
      insight is that, rather than learning from scratch, one can take advantage of
      knowledge coming from previously learned categories, no matter how different
      these categories might be. We explore a Bayesian implementation of this idea.
      Object categories are represented by probabilistic models. Prior knowledge is
      represented as a probability density function on the parameters of these models.
      The posterior model for an object category is obtained by updating the prior in
      the light of one or more observations. We test a simple implementation of our
      algorithm on a database of 101 diverse object categories. We compare category
      models learned by an implementation of our Bayesian approach to models learned
      from by Maximum Likelihood (ML) and Maximum A Posteriori (MAP) methods. We find
      that on a database of more than 100 categories, the Bayesian approach produces
      informative models when the number of training examples is too small for other
      methods to operate successfully.

PMID- 16566509
TI  - A shape-from-shading method of polyhedral objects using prior information.
AB  - We propose a new method for recovering the 3D shape of a polyhedral object from
      its single 2D image using the shading information contained in the image and the
      prior information on the object. In a strict sense, we cannot recover the shape
      of a polyhedron from an incorrect line drawing, even if it is practically almost
      correct. In order to overcome this problem, we propose a flexible face
      positioning method that can permit inconsistencies in the recovered shape that
      arise from vertex-position errors contained in incorrect line drawings. Also, we
      propose to use prior information about the horizontality and verticality of
      special faces and the convex and concave properties of the edges in order to
      attain good solutions and present a method of formulating such prior information
      as physical constraints. The shape-from-shading method is formulated as a
      minimization problem of a nonlinear cost function with the nonlinear constraints
      and its solution is searched by a global optimization algorithm. In the
      experiments with a synthetic image and three kinds of real images, shapes that
      are similar to those of the actual objects were recovered in all cases. As a
      result, the proposed method has proven to be effective in the shape recovery of
      simple-shape polyhedral objects.

PMID- 16566510
TI  - Motion analysis of articulated objects from monocular images.
AB  - This paper presents a new method of motion analysis of articulated objects from
      feature point correspondences over monocular perspective images without imposing
      any constraints on motion. An articulated object is modeled as a kinematic chain
      consisting of joints and links, and its 3D joint positions are estimated within a
      scale factor using the connection relationship of two links over two or three
      images. Then, twists and exponential maps are employed to represent the motion of
      each link, including the general motion of the base link and the rotation of
      other links around their joints. Finally, constraints from image point
      correspondences, which are similar to that of the essential matrix in rigid
      motion, are developed to estimate the motion. In the algorithm, the
      characteristic of articulated motion, i.e., motion correlation among links, is
      applied to decrease the complexity of the problem and improve the robustness. A
      point pattern matching algorithm for articulated objects is also discussed in
      this paper. Simulations and experiments on real images show the correctness and
      efficiency of the algorithms.

PMID- 16566511
TI  - Custom-built moments for edge location.
AB  - We present a general construction of functions whose moments serve to locate and
      parametrize step edges within an image. Previous use of moments to locate edges
      was limited to functions supported on a circular region, but our method allows
      the use of "custom-designed" functions supported on circles, rectangles, or any
      desired shape, and with graphs whose shape may be chosen with great freedom. We
      present analyses of the sensitivity of our method to pixelization errors or
      discrepancy between the image and an idealized edge model. The parametric edge
      description yielded by our method makes it especially suitable as a component of
      wedgelet image coding.

PMID- 16566512
TI  - Robust point matching for nonrigid shapes by preserving local neighborhood
      structures.
AB  - In previous work on point matching, a set of points is often treated as an
      instance of a joint distribution to exploit global relationships in the point
      set. For nonrigid shapes, however, the local relationship among neighboring
      points is stronger and more stable than the global one. In this paper, we
      introduce the lotion of a neighborhood structure for the general point matching
      problem. We formulate point matching as an optimization problem to preserve local
      neighborhood structures during matching. Our approach has a simple graph matching
      interpretation, where each point is a node in the graph, and two nodes are
      connected by an edge if they are neighbors. The optimal match between two graphs
      is the one that maximizes the number of matched edges. Existing techniques are
      leveraged to search for an optimal solution with the shape context distance used
      to initialize the graph matching, followed by relaxation labeling updates for
      refinement. Extensive experiments show the robustness of our approach under
      deformation, noise in point locations, outliers, occlusion, and rotation. It
      outperforms the shape context and TPS-RPM algorithms on most scenarios.

PMID- 16566513
TI  - Adaptive support-weight approach for correspondence search.
AB  - We present a new window-based method for correspondence search using varying
      support-weights. We adjust the support-weights of the pixels in a given support
      window based on color similarity and geometric proximity to reduce the image
      ambiguity. Our method outperforms other local methods on standard stereo
      benchmarks.

PMID- 16566514
TI  - A texture-based method for modeling the background and detecting moving objects.
AB  - This paper presents a novel and efficient texture-based method for modeling the
      background and detecting moving objects from a video sequence. Each pixel is
      modeled as a group of adaptive local binary pattern histograms that are
      calculated over a circular region around the pixel. The approach provides us with
      many advantages compared to the state-of-the-art. Experimental results clearly
      justify our model.

PMID- 16566516
TI  - Retrospective and perspectives of thermophilic anaerobic digestion: Part I.

PMID- 16566517
TI  - Fuzzy neural network for flow estimation in sewer systems during wet weather.
AB  - Estimation of the water flow from rainfall intensity during storm events is
      important in hydrology, sewer system control, and environmental protection. The
      runoff-producing behavior of a sewer system changes from one storm event to
      another because rainfall loss depends not only on rainfall intensities, but also
      on the state of the soil and vegetation, the general condition of the climate,
      and so on. As such, it would be difficult to obtain a precise flowrate estimation
      without sufficient a priori knowledge of these factors. To establish a model for
      flow estimation, one can also use statistical methods, such as the neural network
      STORMNET, software developed at Lyonnaise des Eaux, France, analyzing the
      relation between rainfall intensity and flowrate data of the known storm events
      registered in the past for a given sewer system. In this study, the authors
      propose a fuzzy neural network to estimate the flowrate from rainfall intensity.
      The fuzzy neural network combines four STORMNETs and fuzzy deduction to better
      estimate the flowrates. This study's system for flow estimation can be calibrated
      automatically by using known storm events; no data regarding the physical
      characteristics of the drainage basins are required. Compared with the neural
      network STORMNET, this method reduces the mean square error of the flow estimates
      by approximately 20%. Experimental results are reported herein.

PMID- 16566515
TI  - Principal axis-based correspondence between multiple cameras for people tracking.
AB  - Visual surveillance using multiple cameras has attracted increasing interest in
      recent years. Correspondence between multiple cameras is one of the most
      important and basic problems which visual surveillance using multiple cameras
      brings. In this paper, we propose a simple and robust method, based on principal
      axes of people, to match people across multiple cameras. The correspondence
      likelihood reflecting the similarity of pairs of principal axes of people is
      constructed according to the relationship between "ground-points" of people
      detected in each camera view and the intersections of principal axes detected in
      different camera views and transformed to the same view. Our method has the
      following desirable properties: 1) Camera calibration is not needed. 2) Accurate
      motion detection and segmentation are less critical due to the robustness of the
      principal axis-based feature to noise. 3) Based on the fused data derived from
      correspondence results, positions of people in each camera view can be accurately
      located even when the people are partially occluded in all views. The
      experimental results on several real video sequences from outdoor environments
      have demonstrated the effectiveness, efficiency, and robustness of our method.

PMID- 16566519
TI  - Comparison of techniques for the detection of helminth ova in drinking water and
      wastewater.
AB  - Many countries use wastewater for irrigation. The World Health Organization
      established, as reuse guidelines, a maximum value of 1 helminth ovum/L for
      irrigation. Various techniques for enumerating helminth ova in water have been
      published. To determine the most adequate method for Mexico, four techniques were
      compared: the U.S. Environmental Protection Agency (U.S. EPA), membrane-filter,
      Leeds I, and Faust. Two types of water were used: drinking water and municipal
      wastewater effluent. Sensitivity, discrimination coefficients, precision,
      recovery efficiency, and cost were determined. In addition, several unseeded
      wastewater samples were analyzed. For drinking water, U.S. EPA and the membrane
      filter techniques demonstrated comparable results; however, when wastewater was
      used, the membrane technique showed some deficiencies. Because the U.S. EPA
      technique may be used for samples with both high and low solids content, allows
      for the recovery of helminth ova with different specific gravities, and has the
      lowest total cost, it was selected as the best technique.

PMID- 16566518
TI  - Biohydrogen production in continuous-flow reactor using mixed microbial culture.
AB  - The goal of the proposed project was to develop an anaerobic fermentation process
      that converts negative-value organic wastes into hydrogen-rich gas in a
      continuous-flow reactor under different operating conditions, such as hydraulic
      retention time (HRT), heat treatment, pH, and substrates. A series of batch tests
      were also conducted in parallel to the continuous study to evaluate the hydrogen
      conversion efficiency of two different organic substrates, namely sucrose and
      starch. A heat shock (at 90 degrees C for 15 minutes) was applied to the sludge
      in an external heating chamber known as a sludge activation chamber, as a method
      to impose a selection pressure to eliminate non-spore-forming, hydrogen-consuming
      bacteria and to activate spore germination. The experimental results showed that
      the heat activation of biomass enhanced hydrogen production by selecting for
      hydrogen-producing, spore-forming bacteria. The batch feeding at a shorter HRT of
      20 hours (or higher organic loading rate) favored hydrogen production, whereas,
      at a longer HRT of 30 hours, methane was detected in the gas phase. The major
      organic acids of hydrogen fermentation were acetate, butyrate, and propionate. Up
      to 23.1% of influent chemical oxygen demand was consumed in biomass synthesis.
      Batch tests showed that the hydrogen-production potential of starch was lower
      than sucrose, and better conversion efficiency from starch was obtained at a
      lower pH of 4.5. However, addition of sucrose to starch improved the overall
      hydrogen-production potential and hydrogen-production rate. This study showed
      that sustainable biohydrogen production from carbohydrate-rich substrates is
      possible through heat activation of settled sludge.

PMID- 16566520
TI  - Effect of seeding materials and mixing strength on struvite precipitation.
AB  - Struvite precipitation has increasing interest as a technology for removing and
      recovering phosphorus from wastewater streams. Many chemical factors have been
      studied, such as optimum pH values and component-ion molar ratios, yet,
      understanding of physical aspects is lacking. Two physical parameters were
      tested: (1) seeding material addition and (2) mixing. Objectives were to evaluate
      three seeding materials and to optimize mixing conditions for struvite-crystal
      precipitation, growth, and subsequent sedimentation. Results confirm that mixing
      strength and proper seeding materials increase crystal size and improve
      settleability. For unseeded solutions, optimum phosphorus removal was achieved at
      a mixing strength of G = 76 s(-1). Struvite crystals that were added as the
      seeding material provided the best performance with respect to phosphorus removal
      and crystal-size distribution. Overall, this study provided information to
      improve the practical application of struvite precipitation as a phosphorous
      treatment technology for wastewaters, while generating a marketable slow-release
      fertilizer as a product.

PMID- 16566521
TI  - Aerobic and anaerobic membrane bioreactors for municipal wastewater treatment.
AB  - An aerobic bioreactor and an anaerobic bioreactor, each coupled with a
      microfiltration membrane filter (MBR), were operated at different hydraulic
      retention times (HRTs) with primary effluent from the City of Elmhurst, Illinois,
      municipal-wastewater-treatment plant. The soluble chemical oxygen demand (COD)
      removal performance of the anaerobic MBR system was similar to that of the
      aerobic MBR under the same operational conditions, without the added cost of
      aeration. The results indicated that the solids deposition rate on the membrane
      surface was lower in the case of anaerobic MBR compared to the aerobic MBR,
      indicating possible lower loss in water-flux rates. This research found that an
      anaerobic MBR is a feasible and economical option for municipal-wastewater
      treatment plants seeking COD removal by a biological process followed by a
      separate nitrification and denitrification system.

PMID- 16566522
TI  - Sustainable oil and grease removal from synthetic stormwater runoff using bench
      scale bioretention studies.
AB  - One of the principal components of the contaminant load in urban stormwater
      runoff is oil and grease (O&G) pollution, resulting from vehicle emissions. A
      mulch layer was used as a contaminant trap to remove O&G (dissolved and
      particulate-associated naphthalene, dissolved toluene, and dissolved motor oil
      hydrocarbons) from a synthetic runoff during a bench-scale infiltration study.
      Approximately 80 to 95% removal of all contaminants from synthetic runoff was
      found via sorption and filtration. Subsequently, approximately 90% of the sorbed
      naphthalene, toluene, oil, and particulate-associated naphthalene was biodegraded
      within approximately 3, 4, 8, and 2 days after the event, respectively, based on
      decreases in contaminant concentrations coupled with increases of microbial
      populations. These results indicate the effectiveness and sustainability of
      placing a thin layer of mulch on the surface of a bioretention facility for
      reducing O&G pollution from urban stormwater runoff.

PMID- 16566523
TI  - Biological decolorization of reactive anthraquinone and phthalocyanine dyes under
      various oxidation-reduction conditions.
AB  - The decolorization of two anthraquinone dyes (Reactive Blue 4 [RB4] and Reactive
      Blue 19 [RB19]) and two phthalocyanine dyes (Reactive Blue 7 [RB7] and Reactive
      Blue 21 [RB21]) was investigated at an initial dye concentration of 300 mg/L
      using an unacclimated, enrichment culture. The culture was fed a mixture of
      organic compounds and maintained initially under aerobic conditions, and then
      progressively developed anoxic/ anaerobic conditions. Biotransformation-related
      decolorization of the dyes did not take place under aerobic conditions, but use
      of the feed organic mixture and biomass production by the enrichment culture were
      not affected. Complete ammonia removal occurred in the control and all dye
      amended cultures. The development and extent of nitrification were much lower in
      the latter cultures, in which ammonia removal via air stripping was the dominant
      mechanism. Prolonged incubation of the culture under anoxic/anaerobic conditions
      with multiple carbon source additions resulted in a high decolorization extent of
      anthraquinone dyes (over 84%) and only partial decolorization of phthalocyanine
      dyes (49 to 66%). Development of significant methanogenic activity took place in
      the control and, to a lesser extent, in the two phthalocyanine dye-amended
      cultures, but the anthraquinone dyes severely inhibited the development of
      methanogenic activity. The RB4 and RB19 decolorization was attributed to
      nonreversible, microbially mediated dye transformation(s), demonstrated by the
      accumulation of decolorization products with absorbance maxima in the 420- to 460
      nm region. The decolorization of RB4 and RB19 followed Michaelis-Menten kinetics.
      At an initial dye concentration of 300 mg/L, the observed maximum decolorization
      rate per unit biomass was 9.1 and 37.5 mg dye/mg volatile suspended solids x day
      for the RB4 and RB19, respectively. Thus, partial decolorization of reactive
      phthalocyanine dyes and extensive biological decolorization of reactive
      anthraquinone dyes is feasible only under anoxic/anaerobic conditions.

PMID- 16566524
TI  - Thermophilic-anaerobic digestion to produce class A biosolids: initial full-scale
      studies at Hyperion Treatment Plant.
AB  - The highest quality of biosolids is called exceptional quality. To qualify for
      this classification, biosolids must comply with three criteria: (1) metal
      concentrations, (2) vector-attraction reduction, and (3) the Class A pathogen
      density requirements. The City of Los Angeles Bureau of Sanitation Hyperion
      Treatment Plant (HTP) (Playa del Rey, California) meets the first two
      requirements. Thus, the objective of this study was to ensure that HTP's
      biosolids production would meet the Class A pathogen-reduction requirements
      following the time-temperature regimen for batch processing (U.S. EPA, 1993;
      Subsection 32, Alternative 1). Because regulations require the pathogen limits to
      be met at the last point of plant control, biosolids sampling was not limited to
      immediately after the digesters, i.e., the digester outflows. The sampling
      extended to several locations in HTP's postdigestion train, in particular, the
      last points of plant control, i.e., the truck loading facility and the farm for
      land application. A two-stage, thermophilic-continuous-batch process, consisting
      of a battery of six egg-shaped digesters, was established in late 2001 for phase
      I of this study and modified in early 2002 for phase II. As the biosolids were
      discharged from the second-stage digesters, the Salmonella sp. (pathogen) and
      fecal-coliform (indicator) densities were well below the limits for Class A
      biosolids, even though the second-stage-digester temperatures were a few degrees
      below the temperature required by Alternative 1. Salmonella sp. densities
      remained below the Class A limit at all postdigestion sampling locations. Fecal
      coliform densities were also below the Class A limit at postdigestion-sampling
      locations, except the truck-loading facility (phases I and II) and the farm for
      final use of the biosolids (phase II). Although federal regulations require one
      of the limits for either fecal coliforms or Salmonella sp. to be met, local
      regulations in Kern County, California, where the biosolids are land-applied,
      require compliance with both bacterial limits. Additional work identified
      dewatering, cooling of biosolids after the dewatering centrifuges, and
      contamination as possible factors in the rise in density of fecal coliforms.
      These results provided the basis for the full conversion of HTP to the Los
      Angeles continuous-batch, thermophilic-anaerobic-digestion process. During later
      phases of testing, this process was demonstrated to produce fully disinfected
      biosolids at the farm for land application.

PMID- 16566525
TI  - Comparison between direct microscopy and flow cytometry for rRNA-based
      quantification of Candidatus Accumulibacter phosphatis in activated sludge.
AB  - A comparison of the quantification of a specific microbial group in activated
      sludge by fluorescent in-situ hybridization, coupled with either direct
      microscopic counting or flow cytometry, was performed using an enhanced
      biological-phosphorus-removal, sequencing-batch reactor. The population dynamics
      of Candidatus Accumulibacter phosphatis (Cand. A. phosphatis) was evaluated
      during two separate runs of the reactor. With the operational conditions used,
      Cand. A. phosphatis was enriched until a failure in the pH controller eliminated
      its ecological advantage. As a result, the comparison of quantification
      techniques included Cand. A. phosphatis concentrations as low as 11% and as high
      as 96% of the total cells in the samples. The analysis demonstrated that,
      regardless of the particular limitations of each technique, both provided similar
      results when the activated-sludge flocs were easily dispersed. However, when the
      activated-sludge samples contained flocs that were difficult to disperse, flow
      cytometry failed to provide quantitative results.

PMID- 16566526
TI  - A rapid, direct measurement of bacterial growth rate in anaerobic wastewater
      treatment.
AB  - Reliable design and operation of biological wastewater treatment systems demand
      robust models of biological degradation processes. However, methods to directly
      measure key bacterial growth kinetics have not been readily available. Those
      methods that are available rely on the classic measurement of aerobic respiration
      using oxygen uptake take rates. This paper shows how the thymidine assay can be
      used as a rapid and direct measurement of bacterial specific growth rates (mu) in
      situ for an anaerobic treatment process, independent of aerobic respiration. A
      filtration-based assay is applied and evaluated a dispersed-phase high-rate
      anaerobic treatment process, with results obtained in less than an hour. The
      chemical oxygen demand (COD) biomass in the reactor was 0.52 kg COD m(-3) and the
      specific growth rate of these anaerobic bacteria was 0.8 +/- 0.2 d(-1). It took
      the bacterial populations 21.6 hours to double. This is an important advancement
      from existing methods that use aerobic respiration as a pseudo measurement of
      bacterial specific growth rates. The method allows rapid and direct measures of
      microbial growth rates for anaerobic treatment processes.

PMID- 16566527
TI  - Biological phosphate uptake and release: effect of pH and magnesium ions.
AB  - Enhanced biological phosphorus removal (EBPR) is based on poly-phosphate
      accumulating organisms' (PAOs) unique features of "luxury" phosphate uptake
      during aerobic conditions and phosphate release in anaerobic conditions. It is
      believed that poly-phosphate accumulation is accompanied by the uptake and
      accumulation of potassium ions (K+) and magnesium ions (Mg2+). The release of
      phosphate under anaerobic conditions is also accompanied by the release of both
      cations. The objective of this research was to evaluate the effect of pH and Mg2+
      on the biological phosphate uptake and release behavior of activated sludge mixed
      liquor during aeration and sedimentation. Research results indicate that Mg2+,
      supplied either by magnesium chloride (MgCl2) or magnesium hydroxide [Mg(OH)2],
      stimulated phosphate uptake during the aeration period, while pH increase, caused
      by the application of Mg(OH)2, enhanced phosphate release during the
      sedimentation period. It is also noted in our experiments with MgCl2 that Mg2+
      slightly inhibited anaerobic phosphate release.

PMID- 16566528
TI  - Bioleaching of zinc and copper from anaerobically digested swine manure: effect
      of sulfur levels and solids contents.
AB  - Anaerobically digested swine manure (ADSM) generally contains high concentrations
      of zinc (Zn) and copper (Cu). These metals levels exceed the land application
      regulations of municipal biosolids of many European countries and are on the
      borderline of exceptional quality in the U.S. Environmental Protection Agency
      (U.S. EPA) 40 CFR part 503 standards. From this perspective, a series of batch
      tests were conducted to evaluate the feasibility of bioleaching of Zn and Cu from
      ADSM so that the produced biosolids could safely be applied to land. The effect
      of different substrate levels (sulfur) and total solids content (as high as 9%)
      on metal solubilization was investigated. The results showed that metal
      solubilization efficiency for both Zn and Cu declined significantly with an
      increase in total solids from 3 to 6% and then to 9% at the same substrate level.
      Metal solubilization increased proportionately with increases in substrate
      concentration up to 6% of total solids content. However, at 9% total solids
      content, metal solubilization was insignificant at all substrate levels tested.
      At a 6% total solids level and 10 000 mg/L of substrate, 94% of Zn and 72% of Cu
      were solubilized. Bioleaching was also found to be effective in destruction of
      pathogens with approximately 2.5 log-scale reduction. The residual biosolid was
      found to meet the Class A biosolids standands of U.S. EPA 40 CFR part 503.

PMID- 16566529
TI  - Enhanced anaerobic biodegradability and inactivation of fecal coliforms and
      Salmonella spp. in wastewater sludge by using microwaves.
AB  - During continuous operation of three mesophilic-anaerobic digesters, the effect
      of microwave irradiation, as sludge thermal pretreatment (60 to 65 degrees C),
      was studied. The fecal coliforms log inactivation for microwaved/digested sludge
      was 4.2 +/- 0.4, whereas for conventionally heated/digested sludge and control
      were 2.9 +/- 0.5 and 1.5 +/- 0.5, respectively. In the case of Salmonella spp.,
      no colonies were detected in 85% of the microwaved/digested samples. Considering
      the detection limit, the log inactivation of these samples was greater than 2.0
      +/- 0.3. The conventionally heated/digested sludge and control showed log
      inactivations of 1.9 +/- 0.2 and 1.1 +/- 0.3, respectively. At the 95% confidence
      level, microwaved/digested sludge increased the biogas production by 16.4 +/-
      5.6% and 6.3 +/- 2.4%, as compared to control and conventionally heated/digested
      sludge, respectively. When thermally treated sludge was analyzed for soluble
      chemical oxygen demand, microwaved waste-activated sludge showed considerable
      solubilization between 37 and 60 degrees C. Microwaved/digested sludge showed a
      reduction of capillary suction times by 11.1 +/- 5.9% and 10.7 +/- 5.6%, as
      compared to control and conventionally heated/digested sludge, respectively.

PMID- 16566530
TI  - Who will follow?

PMID- 16566531
TI  - Emotional implications of working in a burn unit.
AB  - Burnout is a syndrome that has been characterized by emotional exhaustion,
      depersonalization, and reduced personal accomplishment associated with chronic
      occupational stressors. The purpose of this study was to determine the prevalence
      of burnout in healthcare professionals involved in primary burn care and to gain
      an understanding of the stressors and pleasures they experience. A cross
      sectional survey was administered between February and March 2004 to healthcare
      professionals working in the burn unit (BU, study group) and critical care unit
      (CrCU, control group) of a teaching hospital. Three questionnaires were
      administered: a demographic data sheet, the Maslach Burnout Inventory (MBI), and
      a questionnaire evaluating sources of stress, pleasures of work, and coping
      mechanisms used by staff. All 75 surveys distributed were completed (BU=36,
      CrCU=39). Respondents from the BU were nurses (66.7%), occupational or physical
      therapists (11.1%), physicians (8.3%), respiratory therapists (5.6%), social
      workers (2.8%), and others (5.6%). There were no significant differences between
      BU and CrCU professionals in years of experience on the unit (6.7 vs 8.0 years),
      years in the field (16.5 vs 14.7 years), weekly hours of patient care (35.1 vs
      39.6 hours), and number of ventilated patients cared for per month (8.4 vs 19.3
      patients). On the MBI, there were no significant differences between units with
      respect to the emotional exhaustion and personal accomplishment subscales.
      However, staff in the BU reported lower rates of depersonalization (P=.049)
      compared with the CrCU counterparts. There was no significant difference in the
      perceived sources of workplaces stressors, but differences existed in the coping
      mechanisms. BU professionals exercised less (P=.007), talked less with their
      families (P=.006), ate less (P=.002), and watched less television (P=.002)
      compared with CrCU professionals as a means of coping with their workplace
      stress. In conclusion, although BU and CrCU have similar work environments, BU
      staff was significantly less depersonalized compared with CrCU staff. However,
      the two units had comparable rates of emotional exhaustion and depersonalization.
      The mechanisms for coping with workplace stress differed significantly between
      the two units.

PMID- 16566532
TI  - Phenomenology in the context of burn care: from "a correct judgment" to "a
      judgment with convinced validity".

PMID- 16566533
TI  - T cells of the gammadelta T-cell receptor lineage play an important role in the
      postburn wound healing process.
AB  - Although gammadelta T cells have been implicated in various aspects of the dermal
      wound healing process, their role in postburn wound healing processes has not
      been investigated. To study this, we subjected mice deficient in gammadelta T
      cells (ie, T-cell receptor delta gene [delta TCR]) and wild-type (WT; C57BL6J)
      mice to burn injury (25% TBSA) or sham treatment; skin samples were isolated 3
      days later. Marked inflammation of the injury site was observed in WT mice but
      was markedly reduced in delta TCR mice. Postinjury fibroblast growth factor,
      platelet-derived growth factor granulocyte-colony stimulating factor levels, and
      nitrite/nitrate were elevated in skin samples from injured WT mice, whereas skin
      tissue levels of these growth factors and inflammatory mediators was
      significantly atteunuated in delta TCRmice. In conclusion, these findings support
      the concept that gammadelta T cells are important to postburn wound healing via
      the production of growth factors and, potentially, regulation of inducible nitric
      oxide synthase activation.

PMID- 16566534
TI  - Long-term follow-up of patients treated for toxic epidermal necrolysis.
AB  - Patient outcomes concerning toxic epidermal necrolysis (TEN) have improved over
      the years as a better understanding of the pathophysiology of the illness has
      been gained and enhancements have been made in the care of the acutely ill. With
      increase in survival, long-term complications these patients experience are
      beginning to be recognized. In this study, we analyzed the outcomes of a cohort
      of TEN survivors treated at our burn unit and sought to determine the impact of
      clinical variables from the initial hospitalization on mortality after discharge.
      We performed a retrospective review of data from patients with TEN treated at our
      burn unit from March 1993 to September 2002. Follow-up data on new health
      problems were collected on patients who were alive at discharge via
      questionnaire. Survival was estimated using the Kaplan-Meier method with Cox
      regression model. During the study period, of the 64 patients treated for TEN, 46
      survived. After discharge, 15 patients died, whereas the remaining 31 patients
      continued to suffer from ocular (54%), skin (81%), and renal (23%) problems.
      Median survival for the whole cohort has not been reached, with an estimated 5
      year survival of 65%. No patient in either group had a TEN recurrence. Seventy
      nine percent of the patients with ocular involvement in the acute phase of TEN
      had long-term ocular complications, and 73% of patients with mucosal involvement
      had persistent mucosal lesions. Five individual factors were found to be
      predictors of postdischarge mortality on univariate analysis: age at diagnosis of
      TEN>or=60 years, SCORTEN 3 to 6, % maximal TBSA slough>or=50%, days from onset of
      symptoms to admission to a burn unit>or=5 days, and presence of multiple
      comorbidities at diagnosis of TEN. In multivariate analysis, only SCORTEN of 3 to
      6 (P=.003) and days to admission>or=5 (P=.027) maintained significance as
      predictors of mortality and may be used to heighten surveillance during
      postdischarge care of patients with TEN.

PMID- 16566535
TI  - Fourth-degree burns to the lower extremity with exposed tendon and bone: a ten
      year experience.
AB  - Fourth-degree extremity burns involve muscle, tendon, and bone, often leading to
      amputation or significant functional impairment. We report our 10-year experience
      (1995-2004) at an urban burn center with fourth-degree burns to the lower
      extremity to characterize treatments and outcomes. Twenty-one patients (40
      limbs), mean age of 45 years, were treated for fourth-degree lower-extremity
      burns with the average extremity burn size of 24% TBSA (range, 2-36%) and a mean
      fourth-degree burn size of 9% TBSA (range, 2-18%). A mean of eight operations
      were required for limb salvage. Six free-tissue transfers, 2 fillet flaps, 14
      local flaps, and multiple skin grafts were performed. Five patients underwent
      tibial burring for granulation tissue stimulation, and the subatmospheric
      pressure device was used in eight patients. Seven limb amputations (18%) were
      required in four patients, and 76% of patients were ambulatory on follow-up. The
      mean hospital stay was 76 days with high rates of cellulitis, deep vein
      thrombosis, and bacteremia. Patients treated with flap closure had a significant
      decrease in the number of operations required for limb salvage. Fourth-degree
      lower-extremity burns require multistage reconstructive procedures using multiple
      levels of the reconstructive ladder but limb salvage is possible in a majority of
      cases.

PMID- 16566536
TI  - Semapimod reduces the depth of injury resulting in enhanced re-epithelialization
      of partial-thickness burns in swine.
AB  - Studies suggest that tumor necrosis factor alpha (TNF-alpha) plays a role in burn
      pathogenesis. We conducted a randomized controlled experiment in swine to
      determine whether a novel macrophage inhibitor, semapimod (formerly known as CNI
      1493), would blunt the local production of TNF-alpha, interleukin (IL)-1, and IL
      6 in burns leading to less injury extension and faster re-epithelialization.
      After creating second-degree burns, animals received one or two intravenous
      boluses of semapimod 1 mg/kg or normal saline, and all burns were treated with
      silver sulfadiazine. The depth of follicular necrosis and thrombosis was reduced
      by either one or two doses of semapimod (P=.04 and .02, respectively). However,
      no differences were noted between groups in cytokine levels. Depth of scarring
      was similar in all groups. We conclude that Semapimod reduces the depth of
      follicular necrosis and thrombosis after second-degree burns in swine, indirectly
      resulting in more rapid re-epithelialization. However, this affect does not
      appear to be mediated by reduced local TNF-alpha, IL-1, or IL-6 protein levels.

PMID- 16566537
TI  - Burn injury exacerbates hemodynamic and metabolic responses in rats with
      polymicrobial sepsis.
AB  - The most common and life-threatening complication of severe burn injury is
      infection, which often results in multiple organ failure (MOF). However, the
      mechanism of development of MOF after burn injury associated with infection is
      not fully understood. Our previous studies showed that when polymorphonuclear
      neutrophils (PMNs) are depleted, burn injury-induced increase in microvascular
      permeability to albumin is markedly attenuated. Thus, we hypothesized that the
      combination of burn injury and polymicrobial infection exacerbates PMN
      activation, increases intestinal microvascular permeability to albumin, and
      alters hemodynamics and metabolism more than burn injury or infection alone.
      Sprague-Dawley rats (250-275 g) were divided into four groups. In the burn group,
      rats were subjected to a 30% TBSA burn injury. In the cecal-ligation puncture
      (CLP) group, CLP was performed using a 22-gauge needle with one puncture. In
      burn+CLP group, rats were subjected to CLP immediately after burn procedure. In
      sham group, rats were subjected to sham procedures. Transient polymicrobial
      bacteremia and persistent polymicrobial bacteremia were induced in the CLP group
      and burn+CLP group, respectively. Microvascular permeability, myeloperoxidase,
      and PMN production of elastase and reactive oxygen species increased in the burn
      group and CLP group and further increased in the burn+CLP group. Hemodunamic and
      metabolic alterations on day 1 and 3 after injury correlated with those
      alterations. Although there was only a low mortality in the burn group and CLP
      group, there was a high mortality in burn+CLP group (79%). The mechanism of MOF
      that leads to high mortality in burn injury complicated by infection may involve
      uncontrolled microvascular damage mediated by PMN activation.

PMID- 16566538
TI  - Quantifying collagen type in mature burn scars: a novel approach using histology
      and digital image analysis.
AB  - Using Herovici staining and digital image analysis, we have studied the collagen
      subtype and fiber orientation in mature burn scars. These techniques have shown
      mature burn scars to have increased type I/type III collagen ratios compared with
      normal skin. Additionally, the collagen orientation of burn scars has been shown
      to be thickened, tightly packed, and lacking the "basket weave" appearance of
      normal skin specimens. These techniques allow the differentiation of type I
      collagen from type III collagen, the assessment of collagen orientation, and the
      analysis of scar architecture in terms of epidermis and papillary/reticular
      dermis contribution. These findings are important clinically because collagen
      subtype and fiber orientation may predict future scar activity. Any attempt to
      modify the scarring process can be directly measured and compared using this
      easily reproducible technique.

PMID- 16566539
TI  - Management of blisters in the partial-thickness burn: an integrative research
      review.
AB  - Conflicting recommendations and clinical applications have been given concerning
      best practices for the management of burn blisters associated with partial
      thickness burns. Arguments for the preservation of intact blisters center on the
      idea of naturally occurring biologic protection whereas the debridment of
      blisters has been advocated because of the perceived decreases in wound infection
      and complications. Recurring themes in burn wound management that are considered
      in this debate include infection, healing, functional and aesthetic outcome,
      patient comfort, ease of dressing care, and cost efficiency. The management of
      burn blisters should be supported by evidence across these six categories, should
      match the expertise of the provider, and should use the available resources in
      the practice setting. The purpose of this review is combine the findings of a
      comprehensive review of the published literature with respect to the management
      of blisters in the partial-thickness burn into a clinical guideline for best
      practice based on available evidence.

PMID- 16566540
TI  - Tissue tonometry is a simple, objective measure for pliability of burn scar: is
      it reliable?
AB  - Objective measurement of burn scar response to treatment is important to
      facilitate individual patient care, research, and service development. This work
      examines the validity and reliability of the tonometer as a means of quantifying
      scar pliability. Ten burn survivors were recruited into the study. Triplicate
      measures were taken for each of four scar and one normal skin point. The
      pliability score from the Vancouver Scar Scale also was used as a comparison. The
      tonometer demonstrated a high degree of reliability (intraclass correlation
      coefficients 0.91-0.94). It also was shown to provide a valid measure of
      pliability by quantifying decreased tissue deformation for scar (2.04 +/- 0.45
      mm) compared with normal tissue (3.02 +/- 0.92 mm; t = 4.28, P = .004) and a
      moderate correlation with Vancouver Scar Scale scores. The tissue tonometer
      provides a repeatable, objective index of burn scar pliability. Using the methods
      described, it is a simple, clinically useful technique for monitoring an
      individual's scar.

PMID- 16566541
TI  - A modified dynamic mouth splint for burn patients.
AB  - The prevention and management of microstomia contracture is very important for
      the quality of life in a patient who has experienced facial burns. Mouth opening
      is important for speech, eating, dental hygiene, expression, social interaction,
      psychosocial well being, and administrating general anesthesia. Principles of
      scar management state a need for opposing horizontal, vertical, and
      circumferential forces for effective management of microstomia. At the Royal
      Brisbane and Women's Hospital, horizontal and circumferential stretch was
      provided well; however, a suitable vertical stretch component was required. After
      a literature review, we introduced and trialed a dynamic mouth splint.
      Subsequently, a modified dynamic mouth splint was developed. The presentation
      here of four case studies will demonstrate that the use of the splint in
      combination with current practice has improved mouth opening and consequently
      functional outcomes.

PMID- 16566543
TI  - Bathtub fire: an extraordinary burn injury.

PMID- 16566542
TI  - Face burns caused by flambe drinks.
AB  - This study was conducted to identify the epidemiology of face burns in Korean
      adults caused by flambe drinks in the hope of developing preventive programs. We
      reviewed the medical records of 25 patients with burns caused by flame drinks
      that were admitted to the Hallym Burn Centre, Hangang Sacred Heart Hospital,
      Seoul, Korea, during the 30-month period of July 2002 to December 2004. The
      injuries occurred while drinking and spilling the whisky on the flame (68%)
      during the hours of social gathering and festivity. There were more men than
      women (male:female ratio=21:4); the mean age was 27.5+/-5.7 years (mean 27, range
      21-43 years). Alcohol flames inflicted superficial (56%) to mid-second-degree
      burns in a relatively small area of body (TBSA 3.2+/-3.0%). The head was most
      commonly involved, followed by the upper extremity and trunk. All patients except
      two were treated with observation and daily dressing changes only. The mean
      length of hospital stay was 12.1+/-6.5 (10, 5-25) days. Long-term cosmetic
      outcomes were excellent. Some victims suffered mild corneal (n=4) and ear (n=6)
      burns, without permanent sequelae. Post-traumatic stress disorder and depression
      also were reported. Burn injuries induced by flambe drinks may be prevented by
      increasing public awareness about its danger and the potential risk for corneal
      and facial burns and by implementing a safety policy. All the involved parties-
      public, distillers, and bar and restaurant management--need to coordinate their
      efforts achieve a reduction in injuries.

PMID- 16566544
TI  - The use of hydrogen peroxide for achieving dermal hemostasis after burn excision
      in a patient with platelet dysfunction.
AB  - As a topical hemostatic agent, hydrogen peroxide (3%) has been applied to
      tangential excisions of burn patients. Hydrogen peroxide provides an adjunct to
      topical epinephrine for hemostasis and clinically has been most useful in
      patients with known platelet dysfunction. Hydrogen peroxide should be irrigated
      from the wound bed before the placement of skin grafting because of its potential
      to inhibit wound healing. In our experience, hydrogen peroxide (3%) soaks have
      not resulted in complications related to corrosive damage, oxygen gas formation,
      or lipid peroxidation that are associated with high concentrations of hydrogen
      peroxide (30%). We also have experienced excellent skin graft take at the wound
      bed after using hydrogen peroxide.

PMID- 16566545
TI  - Purpura fulminans in an adult patient with Haemophilus influenzae sepsis: case
      report and review of the literature.
AB  - Purpura fulminans is a rare complication of a coagulopathy or an infection.
      Haemophilus influenzae infection, which has decreased since the haemophilus
      influenzae type B vaccine was initiated, is an unusual initiating cause of
      purpura fulminans. This case is the first reported in the literature of an adult
      who developed purpura fulminans after Haemophilus influenzae sepsis. Her elevated
      beta2 glycoprotein 1 ratio may have contributed to the severity of her disease.
      Although rare, Haemophilus influenzae may precipitate purpura fulminans. Current
      therapy is directed at control of precipitating factors, removal of nonviable
      tissue, treatment of secondary infections, and physiologic support. There also is
      evidence that patients respond well to hyperbaric oxygen therapy, with decreasing
      limb and tissue loss.

PMID- 16566546
TI  - Aesthetic skin branding: a novel form of body art with adverse clinical sequela.
AB  - Branding is a form of body art wherein third-degree burns are inflicted on the
      skin to produce permanent scars. This method of scarification is a common
      practice among many indigenous cultures and has become exceedingly common in
      western societies. As with other forms of body art, branding is not a
      manifestation of a psychiatric disorder but, rather, a method of self-expression.
      The process can be performed through the use of electrocautery, laser, chemicals,
      freezing, and hot metal. Complications arising from the procedure include acute
      infection, transmission of blood-borne pathogens, allergic reactions, and
      sequelae arising from third-degree burns. In addition, skin branding has been
      shown to be associated with substance abuse and high-risk behaviors among
      adolescents. The purpose of this article is to present the following case report
      and review to familiarize clinicians with this dangerous method of body art.

PMID- 16566547
TI  - Coin and currency burn.
AB  - We describe a case of burns purposefully sustained in a patient performing a
      bizarre pub game while under the influence of alcohol. Full-thickness burns were
      sustained through contact with a 50-p UK currency coin essentially heated with
      burning paper. We discuss the nature and ease by which such burns can be
      sustained in the community and the increasing awareness of alcohol abuse as a
      factor in a significant proportion of such self-inflicted burns.

PMID- 16566548
TI  - Acquired-transient factor X deficiency associated with anticardiolipin antibodies
      in a child with extensive burns.
AB  - The article presents the case of an 18-month-old boy with major scald burns
      complicated by acquired F-X deficiency. On the 15th day of hospitalization, the
      patient developed sepsis and fever. He also exhibited bruxism, especially during
      the febrile episodes, which his permanent teeth to luxate and become mobile.
      Pedodontists decided that all the child's teeth should be extracted to ensure
      proper development of the jaw with growth. Twelve hours later, he developed a
      leukemoid reaction, which was attributed to infection with another aerobic
      organism or development of anaerobic bacteremia after teeth extraction. Twenty
      four hours after the extractions, the burn wounds began oozing and there was
      extensive gingival bleeding and epistaxis. Coagulation parameters were assessed
      immediately. Disseminated intravascular coagulation was detected initially and
      was successfully treated with fresh-frozen plasma transfusions, but bleeding from
      the burn wounds and nasal/oral mucous membranes continued. Further testing
      revealed the diagnosis of acquired isolated F-X deficiency linked with
      antiphospholipid antibodies. Treatment with plasmapheresis, steroids, and
      intravenous immunoglobulin was successful. Hypertrophic scar formation was the
      only issue during 7 months of follow-up.

PMID- 16566552
TI  - Dementia as a risk factor for major burns.

PMID- 16566553
TI  - Loperamide: a potential topical analgesic for the treatment of burn pain.

PMID- 16566554
TI  - A critical evaluation of the clinimetrics of laser Doppler as a method of burn
      assessment in clinical practice.
AB  - The estimation of burn depth, which is essential in the management of burns, has
      traditionally been conducted using clinical evaluation, which has problems of
      subjectivity. A number of studies have been conducted assessing the use of laser
      Doppler to estimate burn depth. Some studies have advocated the use of this
      instrument in clinical practice. However, careful evaluation of many studies to
      date reveal a lack of standardization among studies and significant
      methodological problems that affect the validity of the findings in relation to
      the clinical management of burns. Although many studies suggest that the use of
      laser Doppler may be a useful adjunct to clinical evaluation, in a climate of
      evidence-based medicine when strict scientific principles are considered further
      studies are needed to show the tool to be valid and consistently reliable for the
      assessment of burns. Until such time, laser Doppler should remain as a research
      tool.

PMID- 16566555
TI  - Effects of oxandrolone on outcome measures in the severely burned: a multicenter
      prospective randomized double-blind trial.
AB  - Severe burns induce pathophysiologic problems, among them catabolism of lean
      mass, leading to protracted hospitalization and prolonged recovery. Oxandrolone
      is an anabolic agent shown to decrease lean mass catabolism and improve wound
      healing in the severely burned patients. We enrolled 81 adult subjects with burns
      20% to 60% TBSA in a multicenter trial testing the effects of oxandrolone on
      length of hospital stay. Subjects were randomized between oxandrolone 10 mg every
      12 hours or placebo. The study was stopped halfway through projected enrollment
      because of a significant difference between groups found on planned interim
      analysis. We found that length of stay was shorter in the oxandrolone group (31.6
      +/- 3.1 days) than placebo (43.3 +/- 5.3 days; P < .05). This difference
      strengthened when deaths were excluded and hospital stay was indexed to burn size
      (1.24 +/- 0.15 days/% TBSA burned vs 0.87 +/- 0.05 days/% TBSA burned, P < .05).
      We conclude that treatment using oxandrolone should be considered for use in the
      severely burned while hepatic transaminases are monitored.

PMID- 16566557
TI  - Infection control practices in U.S. burn units.
AB  - The purpose of this study was to determine infection control procedures most
      commonly used in burn units in the United States. We used two data collection
      formats: a brief quantitative survey and a brief qualitative interview. Our
      response rate was 75% (104/139). We found wide variability in general infection
      control practices as well as in wound care practices in intensive care units. The
      majority of units reported having written infection control guidelines specific
      to the burn unit. Respondents noted challenges that burn injury presents to
      infection control. A broad range of techniques for preventing device- and
      procedure-related infection also were provided by respondents. Compliance with
      hand washing on the part of physicians and ancillary staff remains a major
      challenge. To improve the quality of infection control and reduce variation in
      practice, we must continue to monitor the types of practices that are delivered,
      provide feedback to providers on how they care for their patients, where evidence
      exists disseminate best practices, and build the evidence base through efficacy
      trials.

PMID- 16566558
TI  - Prospective analysis of nosocomial infection rates, antibiotic use, and patterns
      of resistance in a burn population.
AB  - Despite significant advances in burn care, infection remains a major cause of
      morbidity and mortality in burn patients. We sought to determine accurate
      infection rates, risk factors for infection, and the percentage of infections
      caused by resistant organisms. In addition, we attempted to identify
      interventions to decrease the use of antimicrobial drugs. Data were collected
      prospectively from 157 burn patients admitted to the University of Iowa Carver
      College of Medicine burn treatment center from October 2001 to October 2002. A
      research assistant reviewed the medical record for each patient identified by
      burn surgeons as being infected to determine whether these episodes met the
      infection control criteria for nosocomial infections. The infection control
      assessment agreed with the surgeon's assessment for 16.7% of the pneumonias,
      70.0% of the burn wound infections, 57.1% of the urinary tract infections, and
      70.0% of the bloodstream infections. By multiple logistic regression analysis,
      body surface area burned, comorbidities, and use of invasive devices were
      significantly related to acquisition of nosocomial infections as identified by
      both the burn surgeons and the infection control criteria. Staphylococcus aureus
      and Pseudomonas were the most common resistant organisms identified. In our
      population, surgeons could decrease antimicrobial use by using explicit criteria
      for identifying patients with hospital-acquired infections, limiting
      perioperative prophylaxis to patients at highest risk of infection, and
      decreasing the incidence of nosocomial infection with reduced use of devices and
      strict adherence to aseptic technique.

PMID- 16566559
TI  - Epidemiologic analysis of patients with burns presenting to the burn units of a
      University Hospital Network in Turkey.
AB  - This retrospective study analyzed risk factors in addition to the demographic and
      epidemiological features of 813 burn patients who were admitted to the burn units
      of a University Hospital Network in Turkey during a 6-year period. The study
      consisted of 436 men (53.6%) and 377 women (46.4%; mean age, 31; range, 0-87
      years). The age distribution of the patients peaked at 1 to 6 years and at 35 to
      44 years. The most common types of burns were scalds (63.8%) and flame burns
      (22.1%). The mean TBSA burned was 9.4 +/- 15.3% in adults and 19.8 +/- 18.6% in
      children. The median and mean hospital stays were 16 and 22.8 days, respectively
      (range, 1-114 days). A total of 813 patients were evaluated, leaving only 255
      hospitalized patients. Of the hospitalized patients, 100 (74.6%) underwent
      autografting, 8 (6.0%) underwent amputation, 113 (84.3%) underwent debridment,
      and 76 (56.7%) underwent escharotomy. The mortality rate among hospitalized
      patients was 14.1%. Although this study provides information about the population
      within close proximity to our burn units, there remains a need for a countrywide
      database of burn incidents.

PMID- 16566560
TI  - Acute cholecystitis in burn patients.
AB  - Acute cholecystitis is a complication in critical illnesses, including burns. The
      purpose of this report is to review one institution's experience with this
      complication during a 21-year time period. A computerized burn registry was used
      for data collection and analysis in this retrospective review. Twenty patients
      developed cholecystitis from a total burn admission population of 10,762 in this
      21-year period (0.18%). Mean patient age was 43.5 years, and their mean burn size
      was 37.4% with a mean full-thickness burn size of 23% TBSA. Mean patient length
      of stay was 77.4 days. Sixteen of these patients were intubated and mechanically
      ventilated for a mean of 56 days. Total parental nutrition was required in 12
      patients. The use of total parental nutrition steadily decreased over the length
      of the study, and early enteral tube feed use has become the norm. All but two
      patients were in the Burn Intensive Care Unit at the time of diagnosis. Men
      outnumbered women by three to one. Nine patients with positive sonograms were
      successfully managed without surgical intervention. Two of these patients also
      had positive hydroxy iminodiacetic acid scans. Surgically managed patients were
      treated with both open and laparoscopic cholecystectomy as well as
      cholecystostomy tube placement. Mortality was 25%. Acute cholecystitis remains a
      serious although relatively rare complication in burn patients. Patients often
      have an unreliable physical examination, several possible causes of fever, and
      abnormal laboratory results. A high index of suspicion and sound clinical
      judgment is required to manage this rare-but-challenging problem.

PMID- 16566561
TI  - Trauma severity influences acute stress in young burned children.
AB  - The purpose of this study was to assess the role of trauma severity on subsequent
      symptoms of posttraumatic stress disorder (PTSD) and physiological reactivity in
      a total of 70 children, ranging from 12 to 48 months of age, who were acutely
      burned. Parents were interviewed shortly after the child was admitted to the
      hospital. PTSD symptoms were measured using the Posttraumatic Stress Disorder
      Semi-Structured Interview and Observational Record for Infants and Young Children
      and the Diagnostic Interview for Children and Adolescents. Nurses completed a
      questionnaire about the child's symptoms and recorded the child's physiological
      data throughout the hospital stay. Significant relationships were found between
      severity of childhood trauma and the total number of PTSD symptoms and
      physiological reactivity. This study supports the hypothesis that severity of
      trauma experienced by young children influences psychological and physiological
      stress indicators after burn injuries. These findings provide new directions for
      the assessment and prevention of PTSD in this age group.

PMID- 16566562
TI  - Burns and amputations: a 24-year experience.
AB  - Although the management of the severely burnt extremity poses a significant
      therapeutic dilemma, burn injuries resulting in amputation are uncommon, In such
      cases, however, amputation can reduce the rate of mortality. In a total of 1858
      patients from January 1980 to January 2004, there were 34 amputations in 27
      patients. There were 23 men (age range, 14-64 years) and 4 women (age range, 34
      85 years). The majority of amputations from burns caused by flame injury
      predominantly after motor vehicle accidents, with only eight cases resulting from
      high-voltage electrical injury. Nine patients required immediate amputations,
      with the rest being delayed. There were three deaths, with a survival rate of
      89%. The majority of single lower-limb amputees and only one of seven bilateral
      amputees were independently mobile. The presence of pre-existing psychiatric
      disease significantly impaired rehabilitation. Free tissue transfer and the usage
      of bioengineered materials may help reduce the incidence of amputations.

PMID- 16566563
TI  - Analysis of functional outcomes in patients discharged from an acute burn center.
AB  - Burn patients require careful consideration of their post-discharge needs to
      maximize their recovery. Patient-specific variables or a combination of variables
      that might allow clinicians to develop pathways and objective endpoints for
      appropriate discharge would assist in expediting the patient's post-discharge
      care. While there have been numerous studies examining a single variable and its
      ability to predict outcomes, these studies may not be directly applicable to burn
      patients. A burn clinician must incorporate a number of variables into their
      prediction of discharge disposition and outcomes. Our study included 202 burn
      patients aged 16 and older discharged from the acute burn unit from February 2004
      to June 2005. Descriptive data collection included age, total body surface area,
      location of burn, presence/absence of inhalation injury, gender, length of stay,
      discharge disposition, insurance status, and presence/absence of social support.
      The analysis that also incorporated data containing functional status consisted
      of FIM scores for locomotion, transfers, dressing, and feeding. The
      classification tree analysis was utilized to demonstrate what variables could
      predict discharge disposition. The only variable that could strongly predict
      those patients that went home versus another setting was the FIM locomotion
      score. Of the patients who went home, 87.2% were at or above a supervision level
      for locomotion, whereas 85.2% of the patients not discharged to home were at or
      below a maximal assist level. The level of functional independence at the time of
      a patient's discharge as assessed by the patient's ability to walk was the most
      powerful identifier of their ongoing needs.

PMID- 16566564
TI  - The use of video capture virtual reality in burn rehabilitation: the
      possibilities.
AB  - We independently explored the use of the Sony PlayStation II EyeToy (Sony
      Corporation, Foster City, CA) as a tool for use in the rehabilitation of patients
      with severe burns. Intensive occupational and physical therapy is crucial in
      minimizing and preventing long-term disability for the burn patient; however, the
      therapist faces a difficult challenge combating the agonizing pain experienced by
      the patient during therapy. The Sony PlayStation II EyeToy is a projected, video
      capture system that, although initially developed as a gaming environment for
      children, may be a useful application in a rehabilitative context. As compared
      with other virtual reality systems the EyeToy is an efficient rehabilitation tool
      that is sold commercially at a relatively low cost. This report presents the
      potential advantages for use of the EyeToy as an innovative rehabilitative tool
      with mitigating effects on pain in burn rehabilitation. This new technology
      represents a challenging and motivating way for the patient to immerse himself or
      herself in an alternate reality while undergoing treatment, thereby reducing the
      pain and discomfort he or she experiences. This simple, affordable technique may
      prove to heighten the level of patient cooperation and therefore speed the
      process of rehabilitation and return of functional ability.

PMID- 16566565
TI  - Healing at home: Comparing cohorts of children with medium-sized burns treated as
      outpatients with in-hospital applied Acticoat to those children treated as
      inpatients with silver sulfadiazine.
AB  - Using Acticoat (Smith & Nephew, London, UK), a dressing that requires changing
      only twice per week, we are able to discharge children with medium-sized burns
      for the majority of their acute care. In sizeable wounds, early burn care is
      often too painful to do at home and, therefore, sedative analgesia or anesthesia
      can be provided by the burn unity as necessary. In the interval between
      dressings, the patients remain at home. A cohort of 30 patients treated in this
      fashion between 2000 and 2002 were compared with 73 matched historical controls
      kept as inpatients and treated with silver sulfadiazine. Children treated with
      Acticoat spent, on average, 0.83 days admitted in hospital whereas those treated
      with silver sulfadiazine averaged 13.85 days (P < .001). There was a reduction in
      complications in patients treated with Acticoat and the need for skin grafting
      was not increased. We have been able to facilitate earlier discharges while
      continuing to provide safe and effective comprehensive burn care.

PMID- 16566566
TI  - Effect of recombinant platelet-derived growth factor (Regranex) on wound closure
      in genetically diabetic mice.
AB  - Burns, especially those involving large surface areas, represent a complex wound
      healing problem. Platelet-derived growth factor (PDGF) is released by activated
      platelets to recruit inflammatory cells toward the wound bed. It has effects on
      promoting angiogenesis and granulation tissue formation. However, the
      effectiveness of topical PDGF on wound closure is variable, ranging from little
      improvement observed in pig models to dramatic improvement reported in a diabetic
      mouse model. Here, we sought to determine the effectiveness of commercially sold
      PDGF-BB (Regranex) on wound closure in genetically diabetic mice. C57BL/KsJ
      db+/db+ mice and its host strain bearing dorsal 1.5-cm wounds were divided into
      groups (n = 8 in each group) receiving topical application of either Regranex (10
      microg/wound) or vehicle for 5 consecutive days after wounding. The rate of wound
      closure was analyzed using computerized planimetry. The amount of granulation
      tissue was determined histologically. Our data indicate that diabetic mice
      exhibit a significant delay in wound closure when compared with their host
      strain. Topical application of Regranex did not improve the time to wound closure
      but did significantly increase the amount of granulation tissue. Our current
      study using commercially available Regranex failed to reproduce the previously
      reported finding that PDGF improved wound closure in healing impaired genetically
      diabetic mice.

PMID- 16566567
TI  - Sedation using dexmedetomidine in pediatric burn patients.
AB  - Maintaining appropriate sedation and analgesia in pediatric burn patients can be
      quite challenging and often requires high doses of analgesics and anxiolytics
      because tolerance quickly develops. Escalating doses of opioids and
      benzodiazepines provide little additional benefit while increasing the incidence
      of side effects. Dexmedetomidine (DEX) is a novel alpha2-adrenergic agonist that
      provides sedation, anxiolysis, and analgesia with much less respiratory
      depression than other sedatives. In addition, DEX stimulation of alpha2 receptors
      on pancreatic beta cells may inhibit insulin secretion. Hyperglycemia has not
      been studied specifically in patients receiving DEX. Therefore, we hypothesized
      that DEX would improve sedation compared with our standard sedation regimen. In
      addition, we studied the effects of DEX on blood glucose levels. We performed a
      retrospective chart review of 65 pediatric burn patients (42 boys, 23 girls) in
      the intensive care unit admitted between 2001 and 2004 who received DEX infusion
      because of failure to achieve adequate sedation with our standard regimen of
      opioids and benzodiazepines. We recorded age, TBSA burn size, weight, dose and
      duration of infusion, adequacy of sedation before and after initiation of DEX,
      blood glucose levels before and after DEX, and the presence or absence of
      mechanical ventilation. The mean age was 5 years (range, 0.6-17), burn size was
      36% TBSA (range, 3-94), and weight was 26 kg (range, 8-100). All patients were
      rated "inadequately sedate" before DEX infusion was initiated at 0.2 mug/kg/hr
      and titrated to effect. Twenty-six patients received a loading dose of 1 mug/kg.
      The average duration of DEX infusion was 11 days (range, 2-50), and no
      tachyphylaxis was noted. The mean dose was 0.5 mug/kg/hr (range, 0.1-2).
      Infusions were weaned over the course of 12 to 24 hours without evidence of
      rebound hypertension or withdrawal. With DEX titration, all patients were rated
      "adequately sedate," even though all were sedation failures with opioids and
      benzodiazepines. Eleven of 42 patients receiving ventilatory support were
      extubated while on DEX infusion, and no patient showed evidence of DEX induced
      respiratory depression. Patient's blood glucose levels averaged 121.2 +/- 8.9
      mg/dl while on DEX infusion and 117.1 +/- 12.1 mg/dl while off, a nonsignificant
      difference.

PMID- 16566568
TI  - Ketamine: a safe and effective agent for painful procedures in the pediatric burn
      patient.
AB  - Ketamine is an effective agent when used for sedation during painful bedside
      procedures. We developed a ketamine administration protocol for
      nonanesthesiologists for the purpose of establishing safe monitoring and
      documentation during ketamine sedation procedures. From June 1, 2002, through
      June 30, 2003, a total of 522 sedation events using ketamine were performed; 347
      of these events were analyzed. Seventeen (4.9%) events contained potentially
      adverse outcome indicators, 10 (2.9%) of which required intervention. Eight
      events were airway related and responded to repositioning, supplemental oxygen,
      or bag-valve-mask ventilation. Two patients had a decrease in blood pressure,
      which responded to fluid administration. Total doses of ketamine administered
      were between 6 and 800 mg, for procedures ranging from 1 to 105 minutes, in
      patients weighing between 3 and 111 kg. The development of a strict protocol
      ensures the safe administration of ketamine for the pediatric burn patient.

PMID- 16566570
TI  - Pediatric burns with snap-cap fireworks.
AB  - Snap-caps are marketed as a relatively safe pyrotechnic (explosive) device for
      children 8 years and older. Individually, the snap-caps pose very little threat
      because the amount of explosive compounds contained in each is limited to 1 mg.
      However, the accidental explosion of numerous snap-caps may cause significant
      burns. This study highlights a series of pediatric patients who presented with
      severe second- and third-degree burns as a result of accidental explosion of snap
      caps. Seven patients with snap-caps-related injuries were treated at the
      University of California, San Diego Regional Burn Center from January 1996 to
      April 1999. Study foci included 1) mode and extent of injury, 2) management, 3)
      associated morbidity, and 4) functional outcome. Six patients (84%) required
      hospital admission. Four patients (57%) underwent split-thickness skin grafting
      to repair mean TBSA burns of 4.1% (range, 2-8%). Three patients (43%) received
      aggressive management of burns with topical medications and dressing changes. The
      nature and extent of snap-cap injuries support the contention that snap-caps have
      the potential to harm children to whom they are marketed.

PMID- 16566572
TI  - Elevated circulating leukemia inhibitory factor in patients with extensive burns.
AB  - To investigate circulating cytokine responsiveness in major burns in association
      with the systemic stress response system, we tested hypothalamic-pituitary
      adrenal (HPA) axis markers in extensive burn cases treated in the Department of
      Plastic and Reconstructive Surgery at Nagasaki University. The HPA axis is a
      major stress response system, and the leukemia inhibitory factor (LIF) may be a
      potent mediator of the HPA axis; therefore, circulating LIF levels in burn
      patients were studied. Twenty extensively burned patients (burn surface area,
      >20%), ie, 10 women and 10 men, 37 to 77 years of age (average: 59.1 +/- 12.10
      years), were assessed. Circulating LIF, adrenocorticotropic hormone (ACTH), other
      inflammatory markers, and 24-hour urinary free cortisol excretion levels were
      investigated. LIF levels were greater in patients who died than in those who
      survived (186.1 +/- 80.41, 83.5 +/- 64.49 pg/ml, respectively, P < .001) at 36
      hours after injury. ACTH levels were more significantly elevated in fatal cases
      than in those who survived. (41.3 +/- 8.28, 25.2 +/- 7.84 pg/ml, respectively, P
      < .0001). Twenty-four hour (24 to 48 hours after injury) pooled urinary free
      cortisol excretion levels also were significantly greater in fatal cases than in
      the surviving patient group (235.0 +/- 36.49 microg/day, 69.0 +/- 18.04
      microg/day, respectively, P < .0001). The correlation between serum LIF and urine
      free cortisol was significant (r = .30; P < .01) as was the correlation of serum
      LIF with plasma ACTH (r = .24; P < .01). Serum LIF as well as HPA axis activity
      markers is a good marker of disease severity and prognosis in patients with
      extensive burns.

PMID- 16566573
TI  - Effects of tumor necrosis factor-alpha on the 26S proteasome and 19S regulator in
      skeletal muscle of severely scalded mice.
AB  - The negative nitrogen balance after burns is an important factor in the
      rehabilitation and treatment of burn injury. It is known that the 26s protesome
      system plays a key role in the protein breakdown of skeletal muscle in some
      pathological situations, including burns, although the mechanism of which remains
      poorly understood. The present study surveyed the effect of tumor necrosis factor
      alpha (TNF-alpha) on the 26S proteasome sysytem after burn injury, which is
      thought to be principally responsible for the proteolysis. The means of immuno
      precipitation-deduction and enzyme-linked immunosorbent assay were used to test
      the change of activities and contents of 26S proteasome and 19S regulator in
      skeletal muscle of mice inflicted with 30% TBSA third-degree burns. The genes
      expression of 19S regulator's subunits Psmc2, Psmc5, Psmd1, and Psmd2 were
      examined by the use of reverse-transcription polymerase chain reaction. The
      results showed that TNF-alpha and burn can markedly increased the activities and
      contents of 26S proteasome and 19S regulator in mice skeletal muscle. In
      addition, the expression levels of the 19S regulator's subunits also were
      remarkably increased. The monoclonal antibody to TNF-alpha obviously can diminish
      the increment of the activities and contents of 26S proteasome and 19S regulator
      as much as the expression levels of the 19S regulator's subunits. The results
      suggested that TNF-alpha can activate the 26S proteasome system in skeletal
      muscle, thus enhancing the degradation of protein, which is associated with the
      development of negative nitrogen balance after scald.

PMID- 16566574
TI  - Reuse of skin graft patches for the coverage of skin defects.

PMID- 16566575
TI  - Neuroleptic malignant syndrome associated with metoclopramide in a burn patient.
AB  - Neuroleptic malignant syndrome (NMS) is an uncommon, potentially fatal syndrome
      that occurs with the use of neuroleptic medications. In view of the rarity of
      this syndrome and the overlap with the pathophysiologic manifestations of a burn,
      the burn surgeon may not readily recognize NMS on presentation. We describe the
      case of a 27-year-old man with 15% TBSA burns who developed NMS as a result of
      metoclopramide use. Recognition and treatment resulted in a prompt resolution of
      symptoms. Initial treatment should include immediate withdrawal of all
      neuroleptic agents, measures aimed at decreasing body temperature, supportive
      care, and restoration of dopamine balance. Various authors have advocated
      treatment with various medications, including benzodiazepines, dantrolene, and
      dopaminergic agents. It is important for burn unit personnel to be aware of this
      syndrome because the early institution of therapy can be life saving.

PMID- 16566576
TI  - Secondary abdominal compartment syndrome in children with burns and trauma: a
      potentially lethal complication.
AB  - Acute, rapid, and unimpeded increases in intra-abdominal pressure can lead to
      multiple organ dysfunction defined as the abdominal compartment syndrome (ACS).
      If this develops in the absence of obvious intra-abdominal injury, it has been
      termed secondary ACS (2 degrees ACS). Massive fluid resuscitation in the presence
      of large burns or shock can lead to 2 degrees ACS. The importance of early
      recognition and the need for urgent abdominal decompression have been recognized
      in adults; however, this has not been appreciated in the pediatric population.
      Medical records of four children diagnosed with 2 degrees ACS were reviewed.
      Secondary ACS occurred in three children with burns and in one child with a
      traumatic brain injury. Three children underwent decompressive laparotomy, and
      one underwent successful percutaneous drainage. There were two survivors.
      Secondary ACS may be observed in burnt or traumatized children needing large
      volume resuscitation. Early recognition of 2 degrees ACS by routine bladder
      pressure monitoring in this high-risk group of children may result in earlier
      decompression and a possible decrease in morbidity and mortality.

PMID- 16566577
TI  - Multiple giant disseminated pyogenic granuloma in a burn lesion.
AB  - This case describes a 2-year-old boy who developed multiple giant pyogenic
      granulomas on his left upper extremity secondary to a burn injury caused by
      boiling milk. Here, we present multiple pyogenic granulomas in a burn patient and
      discuss the possible etiologies of the entity. The pyogenic granulomas were
      excised and wounds closed with sutures (primary repair) (primary closure). No
      pyogenic granulomas have recurred after 11 months of follow-up. Pyogenic
      granuloma with multiple dissemination in a burn scar is an extremely rare
      occurrence, and there have been no reports of pyogenic granulomas caused by flame
      and other type of scalding burns such as hot water and oil. The case presented
      here was a burn injury caused by hot milk. The burn etiology, not the burn injury
      itself, is important because all similar cases have the same etiology. We thought
      that this may not be a coincidence and that milk proteins or other components of
      the milk might cause the development of pyogenic granuloma.

PMID- 16566579
TI  - In situ single-molecule imaging with attoliter detection using objective total
      internal reflection confocal microscopy.
AB  - Confocal microscopy is widely used for acquiring high spatial resolution tissue
      sample images of interesting fluorescent molecules inside cells. The fluorescent
      molecules are often tagged proteins participating in a biological function. The
      high spatial resolution of confocal microscopy compared to wide field imaging
      comes from an ability to optically isolate and image exceedingly small volume
      elements made up of the lateral (focal plane) and depth dimensions. Confocal
      microscopy at the optical diffraction limit images volumes on the order of
      approximately 0.5 femtoliter (10(-15) L). Further resolution enhancement can be
      achieved with total internal reflection microscopy (TIRM). With TIRM, an
      exponentially decaying electromagnetic field (near-field) established on the
      surface of the sample defines a subdiffraction limit dimension that, when
      combined with conventional confocal microscopy, permits image formation from <7
      attoL (10(-18) L) volumes [Borejdo et al. (2006) Biochim. Biophys. Acta, in
      press]. Demonstrated here is a new variation of TIRM, focused TIRM (fTIRM) that
      decreases the volume element to approximately 3 attoL. These estimates were
      verified experimentally by measuring characteristic times for Brownian motion of
      fluorescent nanospheres through the volume elements. A novel application for TIRM
      is in situ single-molecule fluorescence spectroscopy. Single-molecule studies of
      protein structure and function are well-known to avoid the ambiguities introduced
      by ensemble averaging. In situ, proteins are subjected to the native forces of
      the crowded environment in the cell that are not present in vitro. The attoL
      fluorescence detection volume of TIRM permits isolation of single proteins in
      situ. Muscle tissue contains myosin at a approximately 120 microM concentration.
      Evidence is provided that >75% of the bleachable fluorescence detected with fTIRM
      is emitted by five chromophore-labeled myosins in a muscle fiber.

PMID- 16566578
TI  - Structural studies of a potent insect maturation inhibitor bound to the juvenile
      hormone esterase of Manduca sexta.
AB  - Juvenile hormone (JH) is an insect hormone containing an alpha,beta-unsaturated
      ester consisting of a small alcohol and long, hydrophobic acid. JH degradation is
      required for proper insect development. One pathway of this degradation is
      through juvenile hormone esterase (JHE), which cleaves the JH ester bond to
      produce methanol and JH acid. JHE is a member of the functionally divergent
      alpha/beta-hydrolase family of enzymes and is a highly efficient enzyme that
      cleaves JH at very low in vivo concentrations. We present here a 2.7 A crystal
      structure of JHE from the tobacco hornworm Manduca sexta (MsJHE) in complex with
      the transition state analogue inhibitor 3-octylthio-1,1,1-trifluoropropan-2-one
      (OTFP) covalently bound to the active site. This crystal structure, the first JHE
      structure reported, contains a long, hydrophobic binding pocket with the solvent
      inaccessible catalytic triad located at the end. The structure explains many of
      the interactions observed between JHE and its substrates and inhibitors, such as
      the preference for small alcohol groups and long hydrophobic backbones. The most
      potent JHE inhibitors identified to date contain a trifluoromethyl ketone (TFK)
      moiety and have a sulfur atom beta to the ketone. In this study, sulfur-aromatic
      interactions were observed between the sulfur atom of OTFP and a conserved
      aromatic residue in the crystal structure. Mutational analysis supported the
      hypothesis that these interactions contribute to the potency of sulfur-containing
      TFK inhibitors. Together, these results clarify the binding mechanism of JHE
      inhibitors and provide useful observations for the development of additional
      enzyme inhibitors for a variety of enzymes.

PMID- 16566581
TI  - Interactions of HIV-1 Gag with assembly cofactors.
AB  - HIV-1 Gag is the only protein required for retroviral particle assembly. There is
      evidence suggesting that phosphatidylinositol phosphate and nucleic acid are
      essential for viruslike particle assembly. To elucidate structural foundations of
      interactions of HIV-1 Gag with the assembly cofactors PI(4,5)P2 and RNA, we
      employed mass spectrometric protein footprinting. In particular, the NHS-biotin
      modification approach was used to identify the lysine residues that are exposed
      to the solvent in free Gag and are protected from biotinylation by direct protein
      ligand or protein-protein contacts in Gag complexes with PI(4,5)P2 and/or RNA. Of
      21 surface lysines readily modified in free Gag, only K30 and K32, located in the
      matrix domain, were strongly protected in the Gag-PI(4,5)P2 complex. Nucleic acid
      also protected these lysines, but only at significantly higher concentrations. In
      contrast, nucleic acids and not PI(4,5)P2 exhibited strong protection of two
      nucleocapsid domain residues: K391 and K424. In addition, K314, located in the
      capsid domain, was specifically protected only in the presence of both PI(4,5)P2
      and nucleic acid. We suggest that concerted binding of PI(4,5)P2 and nucleic acid
      to the matrix and nucleocapsid domains, respectively, promotes protein-protein
      interactions involving capsid domains. These protein-protein interactions must be
      involved in virus particle assembly.

PMID- 16566580
TI  - Interaction of Vitreoscilla hemoglobin with membrane lipids.
AB  - The interaction of the recombinant hemoglobin from Vitreoscilla sp. (VHb) with
      the bacterial membrane of Escherichia coli cells has been investigated by
      measuring the propensity of VHb to interact with monolayers formed by natural
      bacterial phosholipids. The measurements showed that the protein is capable of
      penetrating the monolayers, possibly establishing interactions with the
      hydrophobic acyl chains. VHb is also capable of binding reversibly phospholipids
      and free fatty acids in solution with a strong selectivity toward cyclopropanated
      acyl chain species. Lipid binding occurs within the distal heme pocket as
      demonstrated by a sharp UV-vis spectral change corresponding to a five-coordinate
      to six-coordinate transition of the heme-iron ferric derivative. Oxygen binding
      properties are affected by the presence of the lipid component within the active
      site. In particular, the oxygen affinity is decreased by more than 20-fold in the
      presence of cyclopropanated phospholipids. The kinetic counterpart of the
      decrease in oxygen affinity is manifest in a 10-fold decrease in the ligand
      combination kinetics. Accordingly, the CO and NO combination kinetics were also
      significantly affected by the presence of the bound lipid within the active site.
      These studies indicate that the current functional hypotheses about VHb should
      take into account the association of the protein within the cytoplasmic membrane
      as well as the presence of a phospholipid within the active site. These data
      suggest a possible lipid-induced regulation of oxygen affinity as the basis of
      VHb functioning.

PMID- 16566582
TI  - A thermodynamic comparison of HPr proteins from extremophilic organisms.
AB  - A thermodynamic stability study of five histidine-containing phosphocarrier
      protein (HPr) homologues derived from organisms inhabiting diverse environments
      is described. These HPr homologues are from Bacillus subtilis (Bs), Streptococcus
      thermophilus (St), Bacillus staerothermophilus (Bst), Bacillus halodurans (Bh),
      and Oceanobacillus iheyensis (Oi). Analyses of solvent and thermal denaturation
      experiments provide the cardinal thermodynamic parameters, like deltaG, deltaH,
      deltaS, T(m), and deltaC(p), that characterize the conformational stability for
      each homologue. The homologue from Bacillus staerothermophilus (BstHPr) was
      established as the most thermostable homologue and also the homologue with
      highest deltaG at all temperatures. A good correlation between habitat
      temperature of the organism and thermal stability of the protein is also seen.
      Stability curves (deltaG vs T) for every homologue are also reported; these
      reveal very similar deltaC(p) and temperature of maximum stability (T(S)) values
      for all HPr homologues. Stability curves show that the higher thermal stability
      of some homologues is not a result of change in curvature of the curve or a shift
      to higher temperature, but rather a displacement of the stability curves to
      higher deltaG values. Stability curves also allowed estimation of deltaG at
      habitat temperature of the organisms, and we find good agreement between
      homologues. Electrostatic contributions to stability of each homologue were
      investigated by measuring stability as a function of varying pH and NaCl
      concentration, and our results suggest that most HPr homologues share similar
      electrostatic contributions to stability.

PMID- 16566584
TI  - Kinetic and structural studies on the catalytic role of the aspartic acid residue
      conserved in copper amine oxidase.
AB  - Copper amine oxidase contains a post-translationally generated quinone cofactor,
      topa quinone (TPQ), which mediates electron transfer from the amine substrate to
      molecular oxygen. The overall catalytic reaction is divided into the former
      reductive and the latter oxidative half-reactions based on the redox state of
      TPQ. In the reductive half-reaction, substrate amine reacts with the C5 carbonyl
      group of the oxidized TPQ, forming the substrate Schiff base (TPQ(ssb)), which is
      then converted to the product Schiff base (TPQ(psb)). During this step, an
      invariant Asp residue with an elevated pKa is presumed to serve as a general base
      accepting the alpha proton of the substrate. When Asp298, the putative active
      site base in the recombinant enzyme from Arthrobacter globiformis, was mutated
      into Ala, the catalytic efficiency dropped to a level of about 10(6) orders of
      magnitude smaller than the wild-type (WT) enzyme, consistent with the
      essentiality of Asp298. Global analysis of the slow UV/vis spectral changes
      observed during the reductive half-reaction of the D298A mutant with 2
      phenylethylamine provided apparent rate constants for the formation and decay of
      TPQ(ssb) (k(obs) = 4.7 and 4.8 x 10(-4) s(-1), respectively), both of which are
      markedly smaller than those of the WT enzyme determined by rapid-scan stopped
      flow analysis (k(obs) = 699 and 411 s(-1), respectively). Thus, Asp298 plays
      important roles not only in the alpha-proton abstraction from TPQ(ssb) but also
      in other steps in the reductive half-reaction. X-ray diffraction analyses of
      D298A crystals soaked with the substrate for 1 h and 1 week revealed the
      structures of TPQ(ssb) and TPQ(psb), respectively, as pre-assigned by single
      crystal microspectrophotometry. Consistent with the stereospecificity of alpha
      proton abstraction, the pro-S alpha-proton of TPQ(ssb) to be abstracted is
      positioned nearly perpendicularly to the plane formed by the Schiff-base imine
      double bond conjugating with the quinone ring of TPQ, so that the orbitals of
      sigma and pi electrons maximally overlap in the conjugate system. More
      intriguingly, the pro-S alpha proton of the substrate is released
      stereospecifically even in the reaction catalyzed by the base-lacking D298A
      mutant. On the basis of these results, we propose that the stereospecificity of
      alpha-proton abstraction is primarily determined by the conformation of TPQ(ssb),
      rather than the relative geometry of TPQ and the catalytic base.

PMID- 16566583
TI  - Interaction of C1q with IgG1, C-reactive protein and pentraxin 3: mutational
      studies using recombinant globular head modules of human C1q A, B, and C chains.
AB  - C1q is the first subcomponent of the classical complement pathway that can
      interact with a range of biochemically and structurally diverse self and nonself
      ligands. 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
      specific and differential binding properties toward C1q ligands. It is largely
      considered that C1q-ligand interactions are ionic in nature; however, the
      complementary ligand-binding sites on C1q and the mechanisms of interactions are
      still unclear. To identify the residues on the gC1q domain that are likely to be
      involved in ligand recognition, we have generated a number of substitution
      mutants of ghA, ghB, and ghC modules and examined their interactions with three
      selected ligands: IgG1, C-reactive protein (CRP), and pentraxin 3 (PTX3). Our
      results suggest that charged residues belonging to the apex of the gC1q
      heterotrimer (with participation of all three chains) as well as the side of the
      ghB are crucial for C1q binding to these ligands, and their contribution to each
      interaction is different. It is likely that a set of charged residues from the
      gC1q surface participate via different ionic and hydrogen bonds with
      corresponding residues from the ligand, instead of forming separate binding
      sites. Thus, a recently proposed model suggesting the rotation of the gC1q domain
      upon ligand recognition may be extended to C1q interaction with CRP and PTX3 in
      addition to IgG1.

PMID- 16566585
TI  - Modification of the phylloquinone in the A1 binding site in photosystem I studied
      using time-resolved FTIR difference spectroscopy and density functional theory.
AB  - A phylloquinone molecule (2-methyl-3-phytyl-1,4-naphthoquinone) occupies the A1
      binding site in photosystem I. Previously, we have obtained A1(-)/A1 FTIR
      difference spectra using labeled and unlabeled photosystem I particles and
      proposed assignments for many of the bands in the spectra [Sivakumar, V., Wang,
      R., and Hastings, G. (2005) Biochemistry 44, 1880-1893]. In particular, we
      suggested that a negative/positive band at 1654/1495 cm(-1) in A1(-)/A1 FTIR DS
      is due to a C=O/C-:O mode of the neutral/anionic phylloquinone, respectively. To
      test this hypothesis, we have obtained A1(-)/A1 FTIR DS for menG mutant PS I
      particles. In menG mutant PS I, phylloquinone in the A1 binding site is replaced
      with an analogue in which the methyl group at position 2 of the quinone ring is
      replaced with a hydrogen atom (2-phytyl-1,4-naphthoquinone). In A1(-)/A1 FTIR DS
      obtained using menG mutant PS I particles, we find that the 1654/1495 cm(-1)
      bands are upshifted by approximately 6 cm(-1). To test if such upshifts are
      likely for C=O/C-:O modes of neutral/anionic phylloquinone, we have used density
      functional theory to calculate the "anion minus neutral" infrared difference
      spectra for both phylloquinone and its methyl-less analogue. We have also
      undertaken calculations in which the C4=O carbonyl group of phylloquinone and its
      methyl-less analogue are hydrogen bonded (to a water or leucine molecule). We
      find that, irrespective of the hydrogen bonding state of the C4=O group, the
      C=O/C-:O modes of neutral/reduced phylloquinone are indeed expected to be
      upshifted by at least 6 cm(-1) upon replacement of the methyl group at position 2
      with hydrogen. The calculations also suggest that certain C=C/C-:C modes of
      neutral/reduced phylloquinone do not shift upon replacement of the methyl group.
      On the basis of these calculated results, we suggest which bands in the A1(-)/A1
      FTIR DS may be associated with C=C/C-:C modes of neutral/reduced phylloquinone,
      respectively.

PMID- 16566586
TI  - Identification of a calcium-binding site in the PsbO protein of photosystem II.
AB  - Analysis of the anomalous X-diffraction data reported by Ferreira et al. (PDB
      entry 1S5L) for crystals of photosystem II isolated from Thermosynechococcus
      elongatus indicates that a calcium ion is bound to the PsbO protein. The Ca2+
      binding site is located close to the lumenal exit of a putative proton channel
      leading from the water splitting site.

PMID- 16566587
TI  - Hydrogen peroxide-mediated isoniazid activation catalyzed by Mycobacterium
      tuberculosis catalase-peroxidase (KatG) and its S315T mutant.
AB  - Inhibition of the enzyme Mycobacterium tuberculosis InhA (enoyl-acyl carrier
      protein reductase) due to formation of an isonicotinoyl-NAD adduct (IN-NAD) from
      isoniazid (INH) and nicotinamide adenine dinucleotide cofactor is considered
      central to the mode of action of INH, a first-line treatment for tuberculosis
      infection. INH action against mycobacteria requires catalase-peroxidase (KatG)
      function, and IN-NAD adduct formation is catalyzed in vitro by M. tuberculosis
      KatG under a variety of conditions, yet a physiologically relevant approach to
      the process has not emerged that allows scrutiny of the mechanism and the origins
      of INH resistance in the most prevalent drug-resistant strain bearing
      KatG[S315T]. In this report, we describe how hydrogen peroxide, delivered at very
      low concentrations to ferric KatG, leads to efficient inhibition of InhA due to
      formation of the IN-NAD adduct. The rate of adduct formation mediated by wild
      type KatG was about 20-fold greater than by the isoniazid-resistant KatG[S315T]
      mutant under optimal conditions (H2O2 supplied along with NAD+ and INH). Slow
      adduct formation also occurs starting with NADH and INH, in the presence of KatG
      even in the absence of added peroxide, due to endogenous peroxide. The poor
      efficiency of the KatG[S315T] mutant can be enhanced merely by increasing the
      concentration of INH, consistent with this enzyme's reduced affinity for INH
      binding to the resting enzyme and the catalytically competent enzyme intermediate
      (Compound I). Origins of drug resistance in the KatG[S315T] mutant enzyme are
      analyzed at the structural level through examination of the three-dimensional X
      ray crystal structure of the mutant enzyme.

PMID- 16566588
TI  - 2'-Fluoroarabino- and arabinonucleic acid show different conformations, resulting
      in deviating RNA affinities and processing of their heteroduplexes with RNA by
      RNase H.
AB  - 2'-Deoxy-2'-fluoro-arabinonucleic acid (FANA) and arabinonucleic acid (ANA)
      paired to RNA are substrates of RNase H. The conformation of the natural DNA/RNA
      hybrid substrates appears to be neither A-form nor B-form. Consistent with this,
      the conformations of FANA and ANA were found to be intermediate between the A-
      and B-forms. However, FANA opposite RNA is preferred by RNase H over ANA, and the
      RNA affinity of FANA considerably exceeds that of ANA. By investigating the
      conformational boundaries of FANA and ANA residues in crystal structures of A-
      and B-form DNA duplexes at atomic resolution, we demonstrate that FANA and ANA
      display subtle conformational differences. The structural data provide insight
      into the structural requirements at the catalytic site of RNase H. They also
      allow conclusions with regard to the relative importance of stereoelectronic
      effects and hydration as modulators of RNA affinity.

PMID- 16566589
TI  - Importance of context in protein folding: secondary structural propensities
      versus tertiary contact-assisted secondary structure formation.
AB  - Molecular dynamics simulations can be used to reveal the detailed conformational
      behaviors of peptides and proteins. By comparing fragment and full-length protein
      simulations, we can investigate the role of each peptide segment in the folding
      process. Here, we take advantage of information regarding the helix formation
      process from our previous simulations of barnase and protein A as well as new
      simulations of four helical fragments from these proteins at three different
      temperatures, starting with both helical and extended structures. Segments with
      high helical propensity began the folding process by tethering the chain through
      side chain interactions involving either polar interactions, such as salt
      bridges, or hydrophobic staples. These tethers were frequently nonnative (i.e.,
      not i --> i + 4 spacing) and provided a scaffold for other residues, thereby
      limiting the conformational search. The helical structure then propagated on both
      sides of the tether. Segments with low stability and propensity formed later in
      the folding process and utilized contacts with other portions of the protein when
      folding. These helices formed via a tertiary contact-assisted mechanism,
      primarily via hydrophobic contacts between residues distant in sequence. Thus,
      segments with different helical propensities appear to play different roles
      during protein folding. Furthermore, the active role of nonlocal side chains in
      helix formation highlights why we must move beyond simple hierarchical models of
      protein folding.

PMID- 16566590
TI  - Analysis of DNA-dependent protein kinase-mediated DNA end joining by two-photon
      fluorescence cross-correlation spectroscopy.
AB  - Nonhomologous end joining (NHEJ) is the primary mechanism by which mammalian
      cells repair DNA double-strand breaks (DSBs). Proteins known to play a role in
      NHEJ include the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), the
      Ku 70/Ku 80 heterodimer (Ku), XRCC4, and DNA ligase IV. One of the main roles of
      the DNA-PKcs-Ku complex is to bring the ends of the DSB together in a process
      termed synapsis, prior to end joining. Synapsis results in the
      autophosphorylation of DNA-PKcs, which is required to make the DNA ends available
      for ligation. Here, we describe a novel assay using two-photon fluorescence cross
      correlation spectroscopy that allows for the analysis of DNA synapsis and end
      joining in solution using purified proteins. We demonstrate that although
      autophosphorylation-defective DNA-PKcs does not support DNA ligase-mediated DNA
      end joining, like wild-type (WT) DNA-PKcs, it is capable of Ku-dependent DNA
      synapsis in solution. Moreover, we show that, in the presence of Ku, both WT DNA
      PKcs and autophosphorylation-defective DNA-PKcs promote the formation of
      multiple, large multi-DNA complexes in solution, suggesting that, rather than
      align two opposing DNA ends, multiple DNA-PK molecules may serve to bring
      multiple DNA ends into the NHEJ complex.

PMID- 16566591
TI  - Transmembrane organization of yeast syntaxin-analogue Sso1p.
AB  - Membrane fusion in secretory pathways is thought to be mediated by SNAREs. It is
      proposed that membrane fusion transits through hemifusion, a condition in which
      the outer leaflets of the bilayers are mixed, but the inner leaflets are not.
      Hemifusion then proceeds to the fusion pore that connects the two internal
      contents. It is believed that the transmembrane domains (TMDs) of the fusion
      proteins play an essential role in the transition from hemifusion to the fusion
      pore. In this work, the structure, dynamics, and membrane topology of the TMD of
      Sso1p, a target membrane (t-) SNARE involved in the trafficking from Golgi to
      plasma membrane in yeast, was investigated using site-directed spin labeling and
      EPR spectroscopy. The EPR analysis of spin-labeled mutants showed that the TMD of
      Sso1p is a well-defined membrane spanning alpha-helix. The results also indicate
      that there is an equilibrium between the monomers and the oligomers. The
      oligomerization is mainly mediated through the interaction at the N-terminal half
      of the TMD, whereas the C-terminal half is free of the tertiary interaction.
      Additionally, the isotropic hyperfine splitting values were examined for
      nitroxide-scanning mutants, and it was found that the hyperfine splitting values
      show a V-shaped profile across the bilayer. Thus, hyperfine splitting may be used
      as an additional parameter to measure bilayer immersion depths of nitroxide.

PMID- 16566592
TI  - Site-directed alkylation of cysteine replacements in the lactose permease of
      Escherichia coli: helices I, III, VI, and XI.
AB  - To complete a study on site-directed alkylation of Cys replacements in the
      lactose permease of Escherichia coli (LacY), the reactivity of single-Cys mutants
      in helices I, III, VI, and XI, as well as some of the adjoining loops, with N
      [14C]ethylmaleimide (NEM) or methanethiosulfonate ethylsulfonate (MTSES) was
      studied in right-side-out membrane vesicles. With the exception of several
      positions in the middle of helix I, which either face the bilayer or are in close
      proximity to other helices, the remaining Cys replacements react with the
      membrane-permeant alkylating agent NEM. In helices III and XI, most Cys
      replacements are also alkylated by NEM except for positions that face the
      bilayer. The reactivity of Cys replacements in helix VI is noticeably lower and
      only 45% of the replacements label. Binding of sugar leads to significant
      increases in the reactivity of Cys residues that are located primarily at the
      same level as the sugar-binding site or in the periplasmic half of each helix.
      Remarkably, studies with small, impermeant MTSES show that single-Cys
      replacements in the cytoplasmic portions of helices I and XI, which line the
      inward-facing cavity, are accessible to solvent from the periplasmic surface of
      the membrane. Moreover, addition of ligand results in increased accessibility of
      Cys residues to the aqueous milieu in the periplasmic region of the helices,
      which may reflect structural rearrangements leading to opening of an outward
      facing cavity. The findings are consistent with the X-ray structure of LacY and
      with the alternating access model [Abramson, J., Smirnova, I., et al. (2003)
      Science 301, 610-615].

PMID- 16566593
TI  - Azotobacter vinelandii vanadium nitrogenase: formaldehyde is a product of
      catalyzed HCN reduction, and excess ammonia arises directly from catalyzed azide
      reduction.
AB  - The Mo-nitrogenase-catalyzed reduction of both cyanide and azide results in the
      production of excess NH3, which is an amount of NH3 over and above that expected
      to be formed from the well-recognized reactions. Several suggestions about the
      possible sources of excess NH3 have been made, but previous attempts to
      characterize these reactions have met with either limited (or no) success or
      controversy. Because V-nitrogenase has a propensity to release partially reduced
      intermediates, e.g., N2H4 during N2 reduction, it was selected to probe the
      reduction of cyanide and azide. Sensitive assay procedures were developed and
      employed to monitor the production of either HCHO or CH3OH (its further two
      electron-reduced product) from HCN. Like Mo-nitrogenase, V-nitrogenase suffered
      electron-flux inhibition by CN- (but was much less sensitive than Mo
      nitrogenase), but unlike the case for Mo-nitrogenase, MgATP hydrolysis was also
      inhibited by CN-. V-Nitrogenase also released more of the four-electron-reduced
      intermediate, CH3NH2, than did Mo-nitrogenase. At high NaCN concentrations, V
      nitrogenase directed a significant percentage of electron flux into excess NH3,
      and under these conditions, substantial amounts of HCHO, but no CH3OH, were
      detected for the first time. With azide, in contrast to the case for Mo
      nitrogenase, both total electron flux and MgATP hydrolysis with V-nitrogenase
      were inhibited. V-Nitrogenase, unlike Mo-nitrogenase, showed no preference
      between the two-electron reduction to N2-plus-NH3 and the six-electron reduction
      to N2H4-plus-NH3. V-Nitrogenase formed more excess NH3, but reduction of the N2
      produced by the two-electron reduction of N3(-) was not its source. Rather, it
      was formed directly by the eight-electron reduction of N3(-). Unlike Mo
      nitrogenase, CO could not completely eliminate either cyanide or azide reduction
      by V-nitrogenase. CO did, however, eliminate the inhibition of both electron flux
      and MgATP hydrolysis by CN-, but not that caused by azide. These different
      responses to CO suggest different sites or modes of interaction for these two
      substrates with V-nitrogenase.

PMID- 16566596
TI  - Engineering diverse changes in beta-turn propensities in the N-terminal beta
      hairpin of ubiquitin reveals significant effects on stability and kinetics but a
      robust folding transition state.
AB  - Using the N-terminal 17-residue beta-hairpin of ubiquitin as a "host" for
      mutational studies, we have investigated the influence of the beta-turn sequence
      on protein stability and folding kinetics by replacing the native G-bulged turn
      (TLTGK) with more flexible analogues (TG3K and TG5K) and a series of four-residue
      type I' beta-turn sequences, commonly found in beta-hairpins. Although a
      statistical analysis of type I' turns demonstrates residue preferences at
      specific sites, the frequency of occurrence appears to only broadly correlate
      with experimentally determined protein stabilities. The subsequent engineering of
      context-dependent non-native tertiary contacts involving turn residues is shown
      to produce large changes in stability. Relatively few point mutations have been
      described that probe secondary structure formation in ubiquitin in a manner that
      is independent of tertiary contacts. To this end, we have used the more rigorous
      rate-equilibrium free energy relationship (Leffler analysis), rather than the two
      point phi value analysis, to show for a family of engineered beta-turn mutants
      that stability (range of approximately 20 kJ/mol) and folding kinetics (190-fold
      variation in refolding rate) are linearly correlated (alpha(f) = 0.74 +/- 0.08).
      The data are consistent with a transition state that is robust with regard to a
      wide range of statistically favored and disfavored beta-turn mutations and
      implicate a loosely assembled beta-hairpin as a key template in transition state
      stabilization with the beta-turn playing a central role.

PMID- 16566594
TI  - Resolution of multiple substrate binding sites in cytochrome P450 3A4: the
      stoichiometry of the enzyme-substrate complexes probed by FRET and Job's
      titration.
AB  - To explore the mechanism of homotropic cooperativity in human cytochrome P450 3A4
      (CYP3A4) we studied the interactions of the enzyme with 1-pyrenebutanol (1-PB), 1
      pyrenemethylamine (PMA), and bromocriptine by FRET from the substrate fluorophore
      to the heme, and by absorbance spectroscopy. These approaches combined with an
      innovative setup of titration-by-dilution and continuous variation (Job's
      titration) experiments allowed us to probe the relationship between substrate
      binding and the subsequent spin transition caused by 1-PB or bromocriptine or the
      type-II spectral changes caused by PMA. The 1-PB-induced spin shift in CYP3A4
      reveals prominent homotropic cooperativity, which is characterized by a Hill
      coefficient of 1.8 +/- 0.3 (S50 = 8.0 +/- 1.1 microM). In contrast, the
      interactions of CYP3A4 with bromocriptine or PMA reveal no cooperativity,
      exhibiting KD values of 0.31 +/- 0.08 microM and 7.1 +/- 2.3 microM,
      respectively. The binding of all three substrates monitored by FRET in titration
      by-dilution experiments at an enzyme:substrate ratio of 1 reveals a simple
      bimolecular interaction with KD values of 0.16 +/- 0.09, 4.8 +/- 1.4, and 0.18 +/
      0.09 microM for 1-PB, PMA, and bromocriptine, respectively. Correspondingly,
      Job's titration experiments showed that the 1-PB-induced spin shift reflects the
      formation of a complex of the enzyme with two substrate molecules, while
      bromocriptine and PMA exhibit 1:1 binding stoichiometry. Combining the results of
      Job's titrations with the value of KD obtained in our FRET experiments, we
      demonstrate that the interactions of CYP3A4 with 1-PB obey a sequential binding
      mechanism, where the spin transition is triggered by the binding of 1-PB to the
      low-affinity site, which becomes possible only upon saturation of the high
      affinity site.

PMID- 16566595
TI  - Aberrant metabolites in mouse models of congenital blinding diseases: formation
      and storage of retinyl esters.
AB  - Regeneration of the visual chromophore, 11-cis-retinal, is a critical step in
      restoring photoreceptors to their dark-adapted conditions. This regeneration
      process, called the retinoid cycle, takes place in the photoreceptor outer
      segments and the retinal pigment epithelium (RPE). Disabling mutations in nearly
      all of the retinoid cycle genes are linked to human conditions that cause
      congenital or progressive defects in vision. Several mouse models with disrupted
      genes related to this cycle contain abnormal fatty acid retinyl ester levels in
      the RPE. To investigate the mechanisms of retinyl ester accumulation, we
      generated single or double knockout mice lacking retinoid cycle genes. All-trans
      retinyl esters accumulated in mice lacking RPE65, but they are reduced in double
      knockout mice also lacking opsin, suggesting a connection between visual pigment
      regeneration and the retinoid cycle. Only Rdh5-deficient mice accumulate cis
      retinyl esters, regardless of the simultaneous disruption of RPE65, opsin, and
      prRDH. 13-cis-Retinoids are produced at higher levels when the flow of retinoid
      through the cycle was increased, and these esters are stored in specific
      structures called retinosomes. Most importantly, retinylamine, a specific and
      effective inhibitor of the 11-cis-retinol formation, also inhibits the production
      of 13-cis-retinyl esters. The data presented here support the idea that 13-cis
      retinyl esters are formed through an aberrant enzymatic isomerization process.

PMID- 16566597
TI  - Role of conserved prolines in the structure and function of the Na+/dicarboxylate
      cotransporter 1, NaDC1.
AB  - The Na+/dicarboxylate cotransporter 1 (NaDC1) is a low-affinity transporter for
      citric acid cycle intermediates such as succinate and citrate. The sequence of
      NaDC1 contains a number of conserved proline residues in predicted transmembrane
      helices (TMs) 7 and 10. These transmembrane domains are of particular importance
      because they may be involved in determining the substrate or cation-binding
      affinity in NaDC1. Four conserved proline residues in TMs 7 and 10 of rabbit
      NaDC1 were replaced with alanine to promote ideal alpha helix or glycine to
      promote free conformation, and the mutant transporters were expressed in the HRPE
      cell line. Mutations of prolines in TM 10 produced decreased protein expression
      and activity, whereas mutations of prolines in TM 7 completely abolished protein
      expression and activity. The chemical chaperone glycerol was found to improve the
      expression of the Pro-351 mutants in TM 7, suggesting that these mutants had
      defects in trafficking. The inactive mutant transporters at position 351 could
      also be rescued by the addition of a proline at a second site. For example, the
      P351A-F347P mutant had restored activity, although its substrate specificity was
      altered. We conclude that, in TM 7, Pro-327 may be of particular importance in
      the function of the transporter, whereas Pro-351 may affect protein targeting.
      The prolines in TM 10, at positions 523 and 524, may not be directly involved in
      the transporter function but may be necessary for maintaining structure.

PMID- 16566598
TI  - Effect of carboxyl-terminal truncation on structure and lipid interaction of
      human apolipoprotein E4.
AB  - Apolipoprotein (apo) E4 has been identified as a major risk factor for
      Alzheimer's disease. Recently, apoE4 was found to undergo proteolytic cleavage in
      Alzheimer's disease brains, resulting in neurotoxic C-terminal-truncated
      fragments. In this study, we examined the effect of progressive truncation of the
      C-terminal domain in apoE4 on its lipid-free structure and lipid binding
      properties. Circular dichroism measurements demonstrated that deletion of
      residues 273-299 or 261-299 significantly decreased the number of helical
      residues, suggesting that the C-terminal residues 261-299 have alpha-helical
      structure. Although the progressive deletions in the C-terminal domain appear to
      somewhat increase thermal stability, apoE4 (delta273-299) and apoE4 (delta261
      299) showed stability similar to that of the apoE4 22-kDa fragment (residues 1
      191) when denatured with guanidine-HCl, indicating that residues 192-272 have a
      negligible effect on the stability of the C-terminal-truncated apoE4. Comparison
      of Trp-264 fluorescence in single Trp mutants of full-length and C-terminal
      truncated apoE4 (delta273-299) indicated that the C-terminal domain structure in
      the latter is both less organized and cooperative. In addition, comparison of the
      binding of the C-terminal-truncated mutants to a hydrophobic fluorescent dye and
      to lipid emulsions revealed that residues 261-272 create a hydrophobic site which
      is critical for lipid binding. These results suggest that removal of a
      hydrophobic C-terminal alpha-helical segment (residues 273-299) to create C
      terminal-truncated apoE4 forms found in brain leads to less organized C-terminal
      structure while still retaining a second alpha-helical lipid-binding region
      (residues 261-272) that is available for interaction with cell membranes and
      other proteins such as amyloid beta peptide.

PMID- 16566599
TI  - Mechanism of the membrane interaction of polynuclear platinum anticancer agents.
      Implications for cellular uptake.
AB  - The interaction between phospholipids and polynuclear platinum drugs was studied
      as a mechanism model for cellular uptake of anticancer drugs. The interaction was
      studied by differential scanning calorimetry (DSC), 31P nuclear magnetic
      resonance spectroscopy (NMR), inductively coupled plasma optical emission
      spectroscopy (ICP-OES), and electrospray ionization mass spectrometry (ESI-MS).
      The transition temperature, enthalpy, and entropy of negatively charged
      phospholipids DPPS, DPPA, and DPPG were changed upon reaction with the trinuclear
      platinum complex [{trans-PtCl(NH3)2}2mu-Pt(NH3)2{H2N(CH2)6NH2}2](NO3)4 (I,
      BBR3464) and the dinuclear analogue [{trans-PtCl(NH3)2}mu
      {(NH2)(CH2)3NH2(CH2)4(NH2)}Cl3 (II, BBR3571). This suggests that these platinum
      complexes interacted not only with the phosphate headgroup but also with the
      region of the fatty acid tail of liposomes and finally changed the fluidity of
      the membrane. Both noncovalent (presumably electrostatic and hydrogen bonding)
      and covalent interactions were involved in the reactions of the negatively
      charged phospholipids DPPA, DPPS, and DPPG with the highly positively charged
      platinum complexes. In contrast, few differences were seen for the zwitterionic
      phospholipids DPPC and DPPE. The binding ratio of BBR3464 to DPPA liposomes was
      higher than the ratio of BBR3464 to DPPS liposomes, and similar differences were
      seen for BBR3571. The binding ratios of the platinum complexes to negatively
      charged phospholipids DPPA, DPPS, and DPPG were slightly lower in a 100 mM
      chloride solution than in a chloride-free solution. The binding of BBR3464 and
      BBR3571 with the liposomes was significantly stronger than that with cis
      [PtCl2(NH3)2], cisplatin. ESI-MS confirmed that the products of the incubation of
      BBR3464 with DPPA and DPPS correspond to chloride displacement and formation of
      [Pt3(NH3)6{NH2(CH2)6NH2}2(DPPA)2]2+ (1) and [Pt3(NH3)6{NH2(CH2)6NH2}2(DPPS)2]2+
      (2), respectively. Similar observations were made for BBR3571. 31P NMR spectra
      confirmed that the site of binding for DPPA was the phosphate oxygen, whereas for
      DPPS, a binding site of the nitrogen of the serine side chain is indicated.
      Noncovalent interactions were also confirmed by use of the analogue
      [{Pt(NH3)3}2mu-Pt(NH3)2{H2N(CH2)6NH2}2](NO3)6 (III, 0,0,0/t,t,t). The
      implications of these results for the mechanism of cellular uptake of polynuclear
      platinum complexes are discussed.

PMID- 16566600
TI  - Incorporation of fragment X into fibrin clots renders them more susceptible to
      lysis by plasmin.
AB  - Bleeding, the most serious complication of thrombolytic therapy with tissue-type
      plasminogen activator (t-PA), is thought to result from lysis of fibrin in
      hemostatic plugs and from the systemic lytic state caused by unopposed plasmin.
      One mechanism by which systemic plasmin can impair hemostasis is by partially
      degrading fibrinogen to fragment X, a product that retains clottability but forms
      clots with reduced tensile strength that stimulate plasminogen activation by t-PA
      more than fibrin clots. The purpose of this study was to elucidate potential
      mechanisms by which fragment X accelerates t-PA-mediated fibrinolysis. In the
      presence of t-PA, clots containing fragment X were degraded faster than fibrin
      clots and exhibited higher rates of plasminogen activation. Although treatment
      with carboxypeptidase B, an enzyme that reduces plasminogen binding to fibrin,
      prolonged the lysis times of fragment X and fibrin clots, clots containing
      fragment X still were degraded more rapidly. Furthermore, plasmin or trypsin also
      degraded clots containing fragment X more rapidly than fibrin clots, suggesting
      that this effect is largely independent of plasminogen activation. Fragment X
      derived degradation products were not preferentially released by plasmin from
      clots composed of equal concentrations of fibrinogen and fragment X, indicating
      that fragment X does not constitute a preferential site for proteolysis. These
      data suggest that structural changes resulting from incorporation of fragment X
      into clots promote their lysis. Thus, attenuation of thrombolytic therapy-induced
      fragment X formation may reduce the risk of bleeding.

PMID- 16566601
TI  - Effect of natural L- to D-amino acid conversion on the organization, membrane
      binding, and biological function of the antimicrobial peptides bombinins H.
AB  - Antimicrobial peptides (AMPs) are evolutionarily old components of innate
      immunity found in all living pluricellular organisms. Interestingly, some
      organisms express families of AMPs with only a slight variation among their
      members, possibly to increase their spectrum of activity. Despite the growing
      body of knowledge about their biological activity and mode of action on bacteria,
      only a few of them have been tested on Leishmania, a worldwide spread protozoan
      pathogen, and the parameters contributing to this activity are yet to be
      determined. We report on the anti-Leishmania activity and mode of action of
      bombinins H2 and H4 isolated from the skin secretion of the frog Bombina
      variegata. H4, the most active, is the first natural AMP of animal origin with a
      single L- to D-amino acid isomerization. Membrane depolarization and membrane
      permeation assays, as well as electron microscopy, suggest that the lethal
      mechanism involves plasma membrane permeation and/or disruption. To better
      understand the enhanced activity of H4, we determined the peptide's structure in
      membranes mimicking those of mammals, bacteria, and Leishmania by using ATR-FTIR
      and CD spectroscopies and assessed their membrane binding by using surface
      plasmon resonance. The data reveal that (i) H2 but not H4 partially aggregates in
      membranes mimicking those of Leishmania, (ii) H2 is slightly more helical than H4
      in all membranes, and (iii) H4 binds the Leishmania model membrane approximately
      5-fold better than H2. This study highlights the importance of a single alpha
      amino acid epimerization as a tool used by nature to modulate the activity of
      AMPs. In addition, our findings suggest bombinins H as potential templates for
      the development of new drugs with a new mode of action against Leishmania.

PMID- 16566602
TI  - Influence of reduction of heme a and Cu(A) on the oxidized catalytic center of
      cytochrome c oxidase: insight from organic solvents.
AB  - Purified bovine heart cytochrome c oxidase (CcO) has been extracted from aqueous
      solution into hexane in the presence of phospholipids and calcium ions. In
      extracts, CcO is in the so-called "slow" form and probably situated in reverse
      micelles. At low water:phospholipid molar ratios, electron transfer from reduced
      heme a and Cu(A) to the catalytic center is inhibited and both heme a3 and Cu(B)
      remain in the oxidized state. The rate of binding of cyanide to heme a3 in this
      oxidized catalytic center is, however, dependent on the redox state of heme a and
      Cu(A). When heme a and Cu(A) are reduced, the rate is increased 20-fold compared
      to the rate when these two centers are oxidized. The enhanced rate of binding of
      cyanide to heme a3 is explained by the destabilization of an intrinsic ligand,
      located at the catalytic site, that is triggered by the reduction of heme a and
      Cu(A).

PMID- 16566603
TI  - Stabilization of the biologically active conformation of the principal
      neutralizing determinant of HIV-1(IIIB) containing a cis-proline surrogate: 1H
      NMR and molecular modeling study.
AB  - The V3 loop is part of the gp120 glycoprotein, an extracellular protein located
      on the membrane of the human immunodeficiency virus (HIV-1). This loop is
      significantly important in many biological processes of the virus and contains
      the principal neutralizing determinant (PND). The PND is one of the most variable
      regions of the envelope, and this is probably related to the ability of the HIV
      virus to escape the immunologic defenses of the target host. Particular attention
      has been paid to the central part of the V3 loop which contains a highly
      conserved GPGR/GPGQ sequence and represents the binding site for antibodies. Many
      attempts have been made to design synthetic peptides as mimics of the V3 loop
      capable of eliciting immune response. However, this strategy suffers from the
      great conformational flexibility small peptides have in solution, which together
      with bioavailability represents the most important limitation to the usefulness
      of synthetic peptides as drugs and as synthetic immunogens. The use of
      conformationally constrained peptides can alleviate this problem. Early works
      using NMR studies have shown that a V3(IIIB) loop-derived peptide is
      conformationally heterogeneous when free in water. Upon complexation with
      0.5beta, a monoclonal neutralizing antibody specific for the HIV-1(IIIB) strain,
      it adopts a beta-hairpin conformation with the central proline forming a type VIb
      beta-turn. In this study, we report the design and characterization of a
      conformationally restricted peptide with a sequence identical to that previously
      described, but with thiazolidine derivatives replacing the proline. The affinity
      of the 2,2-dimethylthiazolidine derivative for 0.5beta demonstrates that this
      moiety can successfully be used to mimic the proline in a cis conformation. This
      peptide not only displays a high propensity to adopt a beta-hairpin conformation
      but also retains the type VIb RGPG beta-turn similar to that found in the native
      complex. These compounds could help in elaborating more efficient immunogens for
      HIV-1 synthetic vaccine development.

PMID- 16566604
TI  - Mn(II) binding by the anthracis repressor from Bacillus anthracis.
AB  - The anthracis repressor (AntR) is a manganese-activated transcriptional regulator
      from Bacillus anthracis and is a member of the diphtheria toxin repressor (DtxR)
      family of proteins. In this paper, we characterize the Mn(II) binding and protein
      dimerization state using a combination of continuous wave (cw) and pulsed EPR
      methods. Equilibrium metal binding experiments showed that AntR binds 2
      equivalents of Mn(II) with positive cooperativity and apparent dissociation
      constants of 210 and 16.6 microM. AntR showed sub-millisecond Mn(II) on-rates as
      measured using stopped-flow EPR. The kinetics of Mn(II) dissociation, measured by
      displacement with Zn(II), was biphasic with rate constants of 35.7 and 0.115 s(
      1). Variable-temperature parallel and perpendicular mode cw EPR spectra showed no
      evidence of a spin-exchange interaction, suggesting that the two Mn(II) ions are
      not forming a binuclear cluster. Finally, size exclusion chromatography and
      double electron-electron resonance EPR demonstrated that AntR forms a dimer in
      the absence of Mn(II). These results provide insights into the metal activation
      of AntR and allow a comparison with related DtxR proteins.

PMID- 16566605
TI  - Functionally relevant coupled dynamic profile of bacteriorhodopsin and lipids in
      purple membranes.
AB  - The dynamics of bacteriorhodopsin (bR) and the lipid headgroups in oriented
      purple membranes (PMs) was determined at various temperatures and relative
      humidity (rh) using solid-state NMR spectroscopy. The 31P NMR spectra of the
      alpha- and gamma-phosphate groups in methyl phosphatidylglycerophosphate (PGP
      Me), which is the major phospholipid in the PM, changed sensitively with
      hydration levels. Between 253 and 233 K, the signals from a fully hydrated sample
      became broadened similarly to those of a dry sample at 293 K. The 15N cross
      polarization (CP) NMR spectral intensities from [15N]Gly bR incorporated into
      fully hydrated PMs were suppressed in 15N CP NMR spectra at 293 K compared with
      those of dry membranes but gradually recovered at low temperatures or at lower
      hydration (75%) levels. The suppression of the NMR signals, which is due to
      interference with proton decoupling frequency (approximately 45 kHz), coupled
      with short spin-spin relaxation times (T2) indicates that the loops of bR, in
      particular, have motional components around this frequency. The motion of the
      transmembrane alpha-helices in bR was largely affected by the freezing of excess
      water at low temperatures. While between 253 and 233 K, where a dynamic phase
      transition-like change was observed in the 31P NMR spectra for the phosphate
      lipid headgroups, the molecular motion of the loops and the C- and N-termini
      slowed, suggesting lipid-loop interactions, although protein-protein interactions
      between stacks cannot be excluded. The results of T2 measurements of dry samples,
      which do not have proton pumping activity, were similar to those for fully
      hydrated samples below 213 K where the M-intermediates can be trapped. These
      results suggest that motions in the 10s micros correlation regime may be
      functionally important for the photocycle of bR, and protein-lipid interactions
      are motionally coupled in this dynamic regime.

PMID- 16566606
TI  - Peroxynitrite-mediated tau modifications stabilize preformed filaments and
      destabilize microtubules through distinct mechanisms.
AB  - Alzheimer's disease (AD) is a progressive amnestic dementia typified by abnormal
      modifications of the microtubule (MT)-associated tau protein that promote its
      pathological self-assembly and displacement from the MT lattice. Previously, we
      showed that peroxynitrite (ONOO-) induces the oxidative 3,3'-dityrosine (3,3'-DT)
      cross-linking and site-selective nitration of tau monomers [Reynolds et al.
      (2005) Biochemistry 44, 1690-1700]. In the present study, we examined the effects
      of ONOO(-)-mediated modifications on two key elements of tau pathobiology: (1)
      the stability of preformed tau filaments and (2) the ability of monomeric tau to
      promote tubulin assembly. Here, we report that treatment of synthetic tau
      filaments with ONOO- generates heat-stable, SDS-insoluble aggregates with a
      significantly reduced mobility by SDS-PAGE compared to that of nontreated
      filaments. Ultrastructurally, these aggregates appear to be cross-linked via
      interfilament bridges. Using LC-MS/MS and HPLC with fluorescent detection, we
      demonstrate that covalent 3,3'-DT linkages are present within these higher-order
      aggregates. Similar to monomeric tau, filamentous tau exhibits a hierarchical
      pattern of nitration following ONOO- treatment with site selectivity toward the
      amino-terminal residues Tyr18 and Tyr29. Further, select nitration of residues
      Tyr18, Tyr29, Tyr197, and Tyr394, events known to stabilize the pathological Alz
      50 conformation [Reynolds et al. (2005) Biochemistry 44, 13997-14009], inhibits
      the ability of monomeric tau to promote tubulin assembly. This effect is specific
      for the 3-NT modification, as mutant tau proteins pseudophosphorylated at each
      Tyr residue are fully competent to stabilize MTs. Collectively, our results
      suggest that ONOO(-)-mediated modifications stabilize tau filaments via 3,3'-DT
      bonding and destabilize MTs by site-selective nitration of tau monomers.
      Moreover, assumption of the Alz-50 conformation may be the mechanism through
      which tau nitration modulates MT stability.

PMID- 16566607
TI  - Assessing the lipid requirements of the Torpedo californica nicotinic
      acetylcholine receptor.
AB  - The lipid requirements of the Torpedo californica nicotinic acetylcholine
      receptor (nAChR) were assessed by reconstituting purified receptors into lipid
      vesicles of defined composition and by using photolabeling with 3-trifluoromethyl
      3-(m-[125I]iodophenyl)diazirine ([125I]TID) to determine functionality. Earlier
      studies demonstrated that nAChRs reconstituted into membranes containing
      phosphatidylcholine (PC), the anionic lipid phosphatidic acid (PA), and
      cholesterol (CH) are particularly effective at stabilizing the nAChR in the
      resting (closed) state that is capable of undergoing agonist-induced
      conformational transitions (i.e., functionality). The present studies demonstrate
      that (1) there is no obligatory requirement for PC, (2) increasing the CH content
      serves to increase the degree to which nAChRs are stabilized in the resting
      state, and this effect saturates at approximately 35 mol % (molar lipid
      percentage), and (3) the effect of increasing levels of PA saturates at
      approximately 12 mol % and in the absence of PA nAChRs are stabilized in the
      desensitized state (i.e., nonfunctional). Native Torpedo membranes contain
      approximately 35 mol % CH but less than 1 mol % PA, suggesting that other anionic
      lipids may substitute for PA. We report that (1) phosphatidylserine (PS) and
      phosphatidylinositol (PI), anionic lipids that are abundant in native Torpedo
      membranes, also stabilize the receptor in the resting state although with reduced
      efficacy (approximately 50-60%) compared to PA, and (2) for nAChRs reconstituted
      into PA/CH membranes at different lipid-protein molar ratios, receptor
      functionality decreases rapidly below approximately 65 lipids per receptor.
      Collectively, these results are consistent with a functional requirement of a
      single shell of lipids surrounding the nAChR and specific anionic lipid- and
      sterol (CH)-protein interactions.

PMID- 16566611
TI  - The state of knowledge of chronic depression.

PMID- 16566612
TI  - Factors associated with health-related quality of life among outpatients with
      major depressive disorder: a STAR*D report.
AB  - OBJECTIVE: Major depressive disorder (MDD) is often chronic and is often
      associated with significant morbidity and mortality. The importance of assessing
      disability and health-related quality of life (HRQOL) in patients with MDD has
      only recently been recognized. The aim of this study was to examine
      sociodemographic and clinical correlates of HRQOL in a large cohort of
      outpatients with MDD. METHOD: Baseline assessments were completed for 1500
      consecutive patients enrolled in the Sequenced Treatment Alternatives to Relieve
      Depression trial, including sociodemographic characteristics and measures of
      depressive symptom severity, clinical features, and HRQOL. Multiple domains of
      HRQOL were assessed with the 12-item Short Form Health Survey, the Work and
      Social Adjustment Scale, and the Quality of Life Enjoyment and Satisfaction
      Questionnaire. The current analyses were conducted on HRQOL data available for
      1397 of the 1500 subjects. RESULTS: Greater symptom severity was associated with
      reduced HRQOL by all measures. Even after age and symptom severity were
      controlled for, a number of clinical features and sociodemographic
      characteristics were independently associated with HRQOL in multiple domains,
      including age at onset of MDD, ethnicity, marital status, employment status,
      education level, insurance status, and monthly household income. CONCLUSION:
      Results strongly suggest the need to assess HRQOL in addition to symptoms in
      order to gauge the true severity of MDD. This study also highlights the necessity
      of measuring HRQOL in multiple domains. These results have implications for the
      assessment of remission and functional recovery in the treatment of MDD.

PMID- 16566614
TI  - Estimating the prevalence and impact of antidepressant-induced sexual dysfunction
      in 2 European countries: a cross-sectional patient survey.
AB  - OBJECTIVE: Sexual dysfunction is a common side effect of antidepressant
      treatment, but recognition of the problem is variable. The aim of this study was
      to estimate the prevalence and impact of sexual dysfunction during antidepressant
      treatment in 2 European countries. METHOD: A cross-sectional survey of 502 adults
      in France and the United Kingdom. All participants were diagnosed with depression
      and taking a selective serotonin reuptake inhibitor (SSRI) or serotonin
      norepinephrine reuptake inhibitor (SNRI), starting within the previous 3 months.
      Information was gathered about other medications and conditions known to impair
      sexual functioning, recent changes in sexual functioning, and the impact of any
      changes. The Medical Outcomes Study 12-Item Short-Form Health Survey and the
      Arizona Sexual Experience Scale were administered to measure health status and
      sexual functioning. Data were collected from June to July of 2002. RESULTS:
      Applying a prevalence estimate algorithm, 26.6% of the French sample and 39.2% of
      the U.K. sample were classified as having antidepressant-induced sexual
      dysfunction; 34.2% of men and 32.5% of women were classified with antidepressant
      induced sexual dysfunction. There was no clear pattern of antidepressant-induced
      sexual dysfunction related to specific antidepressants. Patients with
      antidepressant-induced sexual dysfunction reported that changes in sexual
      functioning negatively affected their self-esteem, mood, and relationships with
      sexual partners. 23.8% of the French sample and 25.2% of the U.K. sample reported
      that they perceived that their partner was dissatisfied with their sex life.
      CONCLUSION: The prevalence of antidepressant-induced sexual dysfunction in this
      study is similar to previous estimates reported in the literature. The impact of
      antidepressant-induced sexual dysfunction is substantial and negatively affects
      quality of life, self-esteem, mood, and relationships with sexual partners.

PMID- 16566613
TI  - The relationship between depression and sleep disturbances: a Japanese nationwide
      general population survey.
AB  - OBJECTIVE: Among the existing epidemiologic studies that have examined the
      relationship between depression and sleep disturbances, there are few nationwide
      studies that have been conducted on subjects representing the general population.
      The present study was therefore conducted to clarify the relationship between
      depression and sleep disturbances, in particular the relationship between
      depression and both sleep duration and subjective sleep sufficiency, using a
      large sample representative of the general population. METHOD: The survey was
      conducted in June 2000, using self-administered questionnaires, targeting a
      population that was selected randomly from among 300 communities throughout
      Japan. Among the respondents, data from 24,686 individuals aged 20 years or older
      were analyzed. The Center for Epidemiologic Studies Depression Scale was used to
      assess the presence of depression. Sleep status, including sleep duration,
      subjective sleep sufficiency, and the presence or absence of insomnia symptoms,
      was evaluated. RESULTS: Those whose sleep duration was less than 6 hours and
      those whose sleep duration was 8 hours or more tended to be more depressed than
      those whose sleep duration was between 6 and 8 hours. Thus, sleep duration
      exhibited a U-shaped association with symptoms of depression. As subjective sleep
      sufficiency decreased, symptoms of depression increased, indicating a linear
      inverse-proportional relationship. CONCLUSION: The fact that sleep duration and
      subjective sleep sufficiency exhibited different relationships with symptoms of
      depression indicates that these 2 sleep parameters each have their own
      significance with regard to depression. These findings may be useful in the
      medical management of mental diseases.

PMID- 16566615
TI  - Levetiracetam for treatment-refractory posttraumatic stress disorder.
AB  - OBJECTIVE: To assess the use of levetiracetam, a novel anticonvulsant agent, in
      the treatment of refractory posttraumatic stress disorder (PTSD). METHOD:
      Retrospective analysis was conducted of 23 patients with DSM-IV diagnosis of PTSD
      who, after being deemed partial or nonresponders to antidepressant therapy,
      received levetiracetam in a naturalistic fashion. The primary outcome measure was
      the PTSD Checklist-Civilian Version (PCL-C). Secondary outcome measures included
      the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for
      Depression (HAM-D), Clinical Global Impressions-Severity of Illness scale (CGI
      S), and Clinical Global Impressions-Improvement scale (CGI-I). RESULTS:
      Levetiracetam at a mean+/-SD dose of 1967+/-650 mg/day for 9.7+/-3.7 weeks was
      generally well tolerated. Nineteen patients (83%) were taking at least 1
      concomitant medication. Patients were severely ill with a mean baseline PCL-C
      score of 67.2+/-9.4, CGI-S score of 6.0+/-0.7, and HAM-A score of 26.8+/-4.9.
      Patients improved significantly on all measures (p<.001). Thirteen patients (56%)
      met responder criteria at endpoint (PCL-C mean change=23.5, CGI-I score<or=2),
      and 6 (26%) met remission criteria (CGI-S score<or=2). Adverse events were
      generally mild, and no patients discontinued levetiracetam because of side
      effects. CONCLUSION: These preliminary data suggest that levetiracetam may be an
      effective treatment in combination with antidepressant therapy for patients with
      PTSD who remain symptomatic after initial intervention.

PMID- 16566616
TI  - Health-related quality of life and functioning of middle-aged and elderly adults
      with bipolar disorder.
AB  - OBJECTIVE: Data characterizing bipolar disorder in older people are scarce,
      particularly on functional status. We evaluated health-related quality of life
      and functioning (HRQoLF) among older outpatients with bipolar disorder as well as
      the relationship of HRQoLF to bipolar illness characteristics. METHOD: We
      compared community-dwelling middle-aged and older adults (age range, 45 to 85
      years) with bipolar disorder (N=54; mean age=57.6 years), schizophrenia (N=55;
      mean age=58.5 years), or no psychiatric illnesses (N=38; mean age=64.7 years) on
      indicators of objective functioning (e.g., education, occupational attainment,
      medical comorbidity) and health status (e.g., Quality of Well-Being scale [QWB]
      and the Medical Outcomes Study-Short Form Health Survey [SF-36]). Within the
      group with bipolar disorder, we examined the relationship between HRQoLF and
      clinical variables (e.g., phase and duration of illness, psychotic symptoms,
      cognitive functioning). RESULTS: Patients with bipolar disorder were similar in
      educational and occupational attainment to the normal comparison group, but they
      obtained lower scores on the QWB and SF-36 (with large effect sizes). Compared
      with schizophrenia, bipolar disorder was associated with better educational and
      work histories but similar QWB and SF-36 scores and more medical comorbidity.
      Patients in remission from bipolar disorder had QWB scores that were worse than
      those of normal comparison subjects. Greater severity of psychotic and depressive
      symptoms and cognitive impairment were associated with lower HRQoLF. CONCLUSIONS:
      Bipolar disorder was associated with substantial disability in this sample of
      older adults, similar in severity to schizophrenia. Remission of bipolar disorder
      was associated with significant but incomplete improvement in functioning,
      whereas psychotic and depressive symptoms and cognitive impairment seemed to
      contribute to lower HRQoLF.

PMID- 16566617
TI  - Treatment adherence among patients with bipolar or manic disorder taking atypical
      and typical antipsychotics.
AB  - OBJECTIVE: This retrospective claims-based study evaluated treatment adherence
      among patients with bipolar or manic disorder treated with atypical and typical
      antipsychotics. METHOD: Claims data for 18,158 antipsychotic treatment episodes
      in 15,224 commercially insured patients with bipolar or manic disorder (ICD-9-CM
      criteria), from January 1999 through August 2003, were evaluated. Overall
      adherence was measured by adherence intensity (medication possession ratio) and
      treatment duration (length of treatment episodes). Treatment-related factors that
      may affect medication adherence were also investigated. Pairwise comparisons of
      the individual atypicals and a combined group of leading typical antipsychotics
      were undertaken using multiple regression analysis adjusting for differing
      patient characteristics. RESULTS: Adherence intensity with quetiapine was 3%
      greater than with the typicals combined (p=.002) and was greater than with
      risperidone or olanzapine by 4% (p<.001) and 2% (p=.001), respectively.
      Olanzapine (2%, p<.001) and ziprasidone (3%, p=.001) showed significantly greater
      adherence intensity than risperidone. Risperidone (p=.002), olanzapine (p=.055),
      and the typicals (p=.021) demonstrated negative associations between dose and
      adherence intensity, while quetiapine showed a nonsignificant trend for a
      positive association (p=.074). Quetiapine and risperidone had significantly
      longer treatment durations than the typicals combined (1.05 and 1.00 months,
      respectively, p<.001) and longer treatment durations than olanzapine (0.75 and
      0.79 months, respectively, p<.001) or ziprasidone (0.78 months, p=.002 and 0.69
      months, p=.003, respectively). Shorter treatment durations were associated with
      switching to other antipsychotics or remaining on or switching to other
      psychotropics (e.g., traditional mood stabilizers) only. All of the atypicals
      except ziprasidone were associated with a significantly lower likelihood of
      switching compared with the typicals (p<.05). CONCLUSIONS: The claims-based
      findings of this study suggest that, for bipolar or manic disorder, quetiapine
      therapy may be associated with better treatment adherence than typical or some
      atypical antipsychotics. Estimated differences, however, were relatively small,
      particularly for adherence intensity.

PMID- 16566618
TI  - Indirect self-destructive behavior and overt suicidality in patients with
      complicated grief.
AB  - BACKGROUND: Complicated grief is associated with increased suicidal ideation in
      samples of bereaved individuals; however, suicidal behavior has not been assessed
      in these patients. Additionally, there are no reports of suicidality among help
      seeking individuals with complicated grief. Therefore, we examined suicidal
      behavior and its correlates in 149 patients who signed informed consent
      statements to participate in a National Institute of Mental Health-funded
      treatment study of complicated grief. METHOD: All patients met criteria for
      complicated grief (Inventory of Complicated Grief score>or=25). Suicidality was
      assessed using a structured clinical interview administered prior to beginning
      treatment. Participants also completed self-report questionnaires and interview
      assessment measures rating the presence or absence of DSM-IV Axis I diagnosis and
      symptom severity. Data were gathered between April 2001 and April 2004. RESULTS:
      Thoughts of wanting to die following the death of a loved one were reported by
      65% of participants. More than half of this group (38% of the study sample)
      engaged in self-destructive behavior, including 9% who made a suicide attempt and
      29% who engaged in indirect suicidal behavior. In a multiple logistic regression
      model, only the severity of complicated grief symptoms (p<.0001) and history of a
      suicide attempt (p<.02) were significantly associated with postloss suicidal
      behavior. DISCUSSION: Consistent with reports of non-help-seeking bereaved
      people, a high rate of individuals seeking treatment for complicated grief
      endorsed a wish to die. Notably, 13% of this group made at least 1 suicide
      attempt, and 44% engaged in indirect self-destructive behavior. Given its
      frequency, this behavior should be included in assessment of bereaved people.

PMID- 16566619
TI  - Efficacy and safety of sildenafil in men with serotonergic antidepressant
      associated erectile dysfunction: results from a randomized, double-blind, placebo
      controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of short-term treatment with sildenafil
      citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile
      dysfunction (ED). METHOD: Men (aged>or=18 years) with major depressive disorder
      (MDD; DSM-IV criteria) in remission and taking SRIs who experienced SRI
      associated ED were enrolled in this multicenter, 6-week, randomized, flexible
      dose, double-blind, placebo-controlled trial. The primary study measures were
      questions 3 (Q3: frequency of penetration) and 4 (Q4: frequency of maintained
      erections after penetration) of the International Index of Erectile Function
      (IIEF) questionnaire. Secondary study measures were all other questions and
      domains of the IIEF, the Erectile Dysfunction Index of Treatment Satisfaction
      (EDITS), a global efficacy questionnaire (GEQ), and a patient-maintained event
      log of sexual activity. RESULTS: Patients receiving sildenafil (N=71) versus
      placebo (N=71) reported significantly higher mean+/-SE scores on Q3 (3.9+/-0.2
      vs. 3.1+/-0.2, p=.003) and Q4 (3.7+/-0.2 vs. 2.8+/-0.2, p<.001) of the IIEF and
      significantly higher scores on all domains of the IIEF. Patients receiving
      sildenafil also reported significantly improved scores on all questions of the
      EDITS questionnaire (p<.02) and the GEQ (p<.0001) and an increased number of
      successful sexual intercourse attempts per week (p<.0001) compared with patients
      receiving placebo. All patients remained in MDD remission (score<or=10 on the
      Hamilton Rating Scale for Depression). Adverse events in patients taking
      sildenafil (vs. placebo) were headache (9% vs. 9%), dyspepsia (9% vs. 1%),
      anxiety (6% vs. 4%), and abnormal vision (3% vs. 0%). CONCLUSIONS: Short-term (6
      week) administration of sildenafil was well tolerated and significantly improved
      erectile function and overall sexual satisfaction in men with ED associated with
      SRI therapy for MDD. Sildenafil may be successfully used to treat SRI-associated
      ED without interruption of antidepressant therapy.

PMID- 16566621
TI  - A single-center, double-blind, placebo-controlled evaluation of lamotrigine in
      the treatment of obesity in adults.
AB  - OBJECTIVE: Unlike many pharmacotherapies for mood disorders, lamotrigine has not
      been shown to be associated with weight gain. This study evaluated the safety and
      efficacy of lamotrigine, compared with placebo, as a monotherapy for weight loss
      in obese adult subjects. METHOD: Forty subjects were randomly assigned (1:1) to
      receive lamotrigine 200 mg/day or placebo for up to 26 weeks. Eligibility
      included a body mass index (BMI) of 30 to < 40. The primary endpoint was the
      change from baseline to endpoint (week 26) in subject weight. Secondary endpoints
      included the change from baseline to endpoint in BMI, percent body fat, serum
      lipid, and glycosylated hemoglobin values, subject satisfaction with treatment,
      and quality of life. RESULTS: Mean change in body weight from baseline to
      endpoint (last observation carried forward) was -6.4+/-10.26 lb and -1.2+/-7.09
      lb for lamotrigine and placebo, respectively (p=.0623). Baseline body weight was
      slightly different between treatment groups (lamotrigine mean=207.9+/-19.88 lb,
      placebo mean=225.0+/-32.70 lb; p=.0588). There was a statistically significant
      difference (p=.0421) in mean change in BMI from baseline to endpoint (-1.5+/-2.78
      and -0.1+/-1.05 for lamotrigine and placebo, respectively). Subjects were more
      satisfied with lamotrigine treatment compared with placebo (p=.0065). There were
      no significant differences between treatment groups in other secondary endpoints.
      The most frequently reported adverse event was mild-to-moderate headache,
      occurring in both treatment groups. CONCLUSION: Lamotrigine demonstrated a
      statistically significant difference in mean change in BMI and a trend toward a
      decrease in body weight and was well tolerated.

PMID- 16566620
TI  - Lifetime comorbidity of DSM-IV mood and anxiety disorders and specific drug use
      disorders: results from the National Epidemiologic Survey on Alcohol and Related
      Conditions.
AB  - OBJECTIVE: To present nationally representative data on the lifetime prevalence
      and comorbidity of 8 specific drug use disorders, separately for abuse and
      dependence, and mood and anxiety disorders. METHOD: Data come from a
      representative sample (N=43,093) of the United States civilian, noninstitutional
      population 18 years and older. Diagnoses of mood, anxiety, and drug use disorders
      were based upon face-to-face personal interviews using the Alcohol Use Disorder
      and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV).
      RESULTS: Associations between specific mood and anxiety disorders and specific
      drug use disorders were virtually all positive and statistically significant
      (p<.05). In general, associations were greater for dependence than abuse, greater
      for mood than anxiety disorders, and in some instances stronger among women than
      men (p<.05). Large odds ratios also were observed for individuals with comorbid
      mood and anxiety disorders. CONCLUSION: The comorbidity between specific mood and
      anxiety disorders and specific drug use disorders is pervasive in the U.S.
      population. Findings suggest that comorbid psychiatric disorders may increase the
      risk of greater involvement in more serious illicit drug use disorders and that
      the greater comorbidity between mood and anxiety and drug use disorders among
      women may reflect greater deviance and psychopathology among drug-using women
      than men. Findings also suggest that drug abuse prevention and intervention
      efforts should address other psychiatric conditions. Further, definitions of drug
      use disorder phenotypes should give careful consideration to other psychiatric
      conditions as meaningful characteristics of case heterogeneity.

PMID- 16566622
TI  - Imipramine is effective in preventing relapse in electroconvulsive therapy
      responsive depressed inpatients with prior pharmacotherapy treatment failure: a
      randomized, placebo-controlled trial.
AB  - OBJECTIVE: To compare the efficacy of imipramine versus placebo in preventing
      relapse after successful electroconvulsive therapy (ECT) in depressive inpatients
      with pharmacotherapy treatment failure prior to ECT. METHOD: During a 6-month
      period, the incidence of relapse was assessed. Two centers, both inpatient units
      for treatment of depressed patients, participated in this trial. Patients with
      DSM-IV-diagnosed major depressive disorder resistant to an anti-depressant and
      subsequent lithium addition and/or a monoamine oxidase inhibitor were included.
      Patients were randomly assigned to double-blind treatment with imipramine with
      adequate plasma levels (N=12) or placebo (N=15) after successful ECT. The mean
      imipramine dosage was 209 mg/day (standard deviation: 91.7, range: 75-325
      mg/day). The main outcome measure was relapse defined as at least "moderately
      worse" compared with baseline score on the Clinical Global Impressions
      Improvement scale. Treatments were compared with survival analysis using the Cox
      proportional hazards model, including psychotic features and the score on the
      Hamilton Rating Scale for Depression (HAM-D) at baseline as prespecified
      covariables. Patients were enrolled in the study from April 1997 to July 2001.
      RESULTS: In the placebo group, 80% (12/15) of the patients relapsed compared with
      18% (2/11) in the imipramine group. The Cox regression analysis showed a
      significant reduction in the risk of relapse of 85.6% with imipramine compared to
      placebo (p=.007; 95% confidence interval [CI]=24.6% to 97.2%) adjusted for the
      covariables. There was an 18% increase in the relapse rate (p=.032; 95% CI=2% to
      36%) per unit increase in HAM-D score before the start of the trial; psychotic
      features had no significant effect (p=.794). CONCLUSIONS: Depressed patients with
      pharmacotherapy treatment failure may benefit from the prophylactic effect of the
      same class of drug during maintenance therapy after response to ECT.

PMID- 16566623
TI  - Response versus remission in obsessive-compulsive disorder.
AB  - OBJECTIVE: To investigate rates of response and remission in adults with
      obsessive-compulsive disorder (OCD) after 12 weeks of evidence-based treatment.
      METHOD: Post hoc analyses of response and remission were conducted using data
      from a multisite, randomized, controlled trial comparing the effects of 12 weeks
      of exposure and ritual prevention (EX/RP), clomipramine (CMI), their combination
      (EX/RP+CMI), or pill placebo (PBO) in 122 adults with OCD (DSM-III-R or DSM-IV
      criteria). Response was defined as a decrease in symptoms; remission was defined
      as minimal symptoms after treatment. Different response and remission definitions
      were constructed based on criteria used in prior studies. For each definition,
      the proportion of responders or remitters in each treatment group was then
      compared. RESULTS: There were significant differences (p<.05) among the 4
      treatment groups in the proportion of responders and remitters. In pairwise
      comparisons, EX/RP+CMI and EX/RP each produced significantly more responders and
      remitters than PBO; CMI produced significantly more responders and remitters than
      PBO for some definitions but not for others. When remission was defined as a Yale
      Brown Obsessive Compulsive Scale (YBOCS) score of 12 or less, significantly more
      EX/RP+CMI (18/31 [58%]) and EX/RP (15/29 [52%]) patients entering treatment
      achieved remission than either CMI (9/36 [25%]) or PBO (0/26 [0%]) patients.
      However, even in treatment completers, many CMI and some EX/RP+CMI and EX/RP
      patients did not achieve remission (remission rates for YBOCS<or=12:
      EX/RP+CMI=13/19 [68%]; EX/RP=15/21 [71%]; CMI=8/27 [30%]; PBO=0/20 [0%]).
      CONCLUSION: EX/RP (with or without CMI) can lead to superior treatment outcome
      compared with CMI alone in OCD patients without comorbid depression. However,
      many OCD patients who receive evidence-based treatment do not achieve remission.

PMID- 16566624
TI  - A randomized controlled trial of cognitive therapy for bipolar disorder: focus on
      long-term change.
AB  - BACKGROUND: This study reports the outcome of a randomized controlled trial of
      cognitive therapy (CT) for bipolar disorder. The treatment protocol differed from
      other published forms of CT for bipolar disorder through the addition of emotive
      techniques. METHOD: Fifty-two patients with DSM-IV bipolar I or II disorder were
      randomly allocated to a 6-month trial of either CT or treatment as usual, with
      both treatment groups also receiving mood stabilizers. Outcome measures included
      relapse rates, dysfunctional attitudes, psychosocial functioning, hopelessness,
      self-control, and medication adherence. Patients were assessed during treatment
      by independent raters blind to the patients' group status. RESULTS: At
      posttreatment, patients allocated to CT had experienced less severe depression
      scores (Beck Depression Inventory and Montgomery-Asberg Depression Rating Scale)
      and less dysfunctional attitudes. After controlling for the presence of major
      depressive episode at baseline, there was a statistical trend toward a greater
      time to depressive relapse (p=.06) for the CT group. At 12-month follow-up, the
      CT group showed a trend toward lower Young Mania Rating Scale scores and improved
      behavioral self-control. The Clinical Global Impressions-Improvement scale,
      comparing the 18 months prior to treatment to the severity of illness status at
      follow-up, showed a substantial difference between groups in favor of CT.
      CONCLUSION: Our findings corroborate previous bipolar disorder research in
      demonstrating the value of CT, particularly immediately post-treatment, and
      indicate some continuation (albeit diminishing) of benefits in the succeeding 12
      months. These findings suggest that psychological booster sessions may be crucial
      for maintaining the beneficial effects of cognitive therapy.

PMID- 16566626
TI  - A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or
      placebo in breast cancer patients (stages I, II, III, and IV) with major
      depression.
AB  - OBJECTIVE: This study compared the efficacy and safety of paroxetine and
      desipramine with those of placebo in the treatment of depressive disorders in
      adult women with breast cancer, stages I-IV. METHOD: In a double-blind, placebo
      controlled study, 35 female outpatients with breast cancer and DSM-III-R major
      depression or adjustment disorder with depressed mood were randomly assigned to
      treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6
      weeks. Primary efficacy was assessed by change from baseline in score on the 21
      item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome
      measure was change from baseline in the Clinical Global Impressions-Severity of
      Illness scale (CGI-S) score. RESULTS: Mean changes in the total HAM-D and CGI-S
      scores from baseline to 6-week endpoint for the paroxetine and desipramine groups
      were not significantly different than those for the placebo-treated group. An
      unusually high rate of response (defined as >or=50% improvement in the HAM-D
      score) in the placebo group was observed (55% [N=6]); adverse events precipitated
      patient discontinuation in the active treatment groups (9% [N=1] for desipramine,
      15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18%
      [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating
      Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic)
      was also similar between groups. CONCLUSION: The small number of women in this
      study most likely contributed to the lack of observed differences in efficacy
      observed during the 6 weeks of treatment. Randomized, placebo-controlled trials
      of adequate power seeking to determine efficacy of antidepressants in the United
      States for the treatment of women with breast cancer and comorbid depression
      remain of paramount importance.

PMID- 16566627
TI  - Menstrual dysfunction prior to onset of psychiatric illness is reported more
      commonly by women with bipolar disorder than by women with unipolar depression
      and healthy controls.
AB  - BACKGROUND: Preliminary reports suggest that menstrual cycle irregularities occur
      more commonly in women with bipolar disorder and unipolar depression than in the
      general population. However, it is not always clear whether such abnormalities,
      reflecting disruption of the hypothalamic-pituitary-gonadal (HPG) axis, are
      caused by psychotropic treatments or associated with the disorder per se. METHOD:
      The prevalence of early-onset (within the first 5 postmenarchal years) menstrual
      cycle dysfunction (menstrual cycle length unpredictable within 10 days or
      menstrual cycle length<25 days or >35 days) occurring before onset of psychiatric
      illness was compared between subjects with DSM-IV bipolar disorder participating
      in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)
      and subjects with DSM-IV unipolar depression or no psychiatric illness
      participating in the Harvard Study of Moods and Cycles. Data from the Harvard
      Study of Moods and Cycles were gathered from September 1995 to September 1997,
      and data from STEP-BD were gathered from November 1999 to May 2001. RESULTS:
      Early-onset menstrual cycle dysfunction was reported to have occurred in 101/295
      women with bipolar disorder (34.2%), 60/245 women with depression (24.5%), and
      134/619 healthy controls (21.7%). Women with bipolar disorder were more likely to
      have early-onset menstrual cycle dysfunction than healthy controls (chi2=16.58,
      p<.0001) and depressed women (chi2=6.08, p=.01), while depressed women were not
      more likely to have early-onset menstrual cycle dysfunction than healthy controls
      (chi2=0.81, p=.37). CONCLUSIONS: Compared with healthy controls and women with
      unipolar depression, women with bipolar disorder retrospectively report early
      onset menstrual dysfunction more commonly prior to onset of bipolar disorder.
      Future studies should evaluate potential abnormalities in the hypothalamic
      pituitary-gonadal axis that are associated with bipolar disorder.

PMID- 16566628
TI  - St. John's wort (Hypericum perforatum) and breastfeeding: plasma and breast milk
      concentrations of hyperforin for 5 mothers and 2 infants.
AB  - BACKGROUND: Herbal preparations for depression, such as St. John's wort, are
      often preferred over pharmaceutical preparations by mothers and midwives after
      childbirth because these preparations are available to patients as over-the
      counter "natural" treatments and are popularly assumed to be safe. The only
      existing report on St. John's wort excretion into human milk showed that only 1
      active component (hyperforin) was detectable in breast milk, but was not
      detectable in the infants' plasma. Another report found more cases of minor
      problems in infants breast-fed by women taking St. John's wort. However,
      significance was reached only in comparison with disease-matched women (p<.01),
      not healthy controls (p=.20). METHOD: Five mothers who were taking 300 mg of St.
      John's wort 3 times daily (LI 160 [Jarsin], Lichtwer Pharma GmbH; Berlin,
      Germany) and their breastfed infants were assessed. Thirty-six breast milk
      samples (foremilk and hindmilk collected during an 18-hour period) and 5 mothers'
      and 2 infants' plasma samples were analyzed for hyperforin levels by tandem mass
      spectrometry (LC/MS/MS; limit of quantification=0.1 ng/mL). Data were gathered
      from January 2001 to February 2002. RESULTS: Hyperforin is excreted into breast
      milk at low levels. However, the compound was at the limit of quantification in
      the 2 infants' plasma samples (0.1 ng/mL). Milk/plasma ratios ranged from 0.04 to
      0.13. The relative infant doses of 0.9% to 2.5% indicate that infant exposure to
      hyperforin through milk is comparable to levels reported in most studies
      assessing anti-depressants or neuroleptics. No side effects were seen in the
      mothers or infants. CONCLUSION: These results add to the evidence of the relative
      safety of St. John's wort while breast-feeding found in previous observational
      studies.

PMID- 16566629
TI  - Recent advances in the treatment of depression in the presence of physical
      symptoms.

PMID- 16566632
TI  - Psychiatric genetics.

PMID- 16566633
TI  - Electroencephalographic abnormalities associated with antidepressant treatment: a
      comparison of mirtazapine, venlafaxine, citalopram, reboxetine, and
      amitriptyline.

PMID- 16566634
TI  - Panic attacks associated with topiramate.

PMID- 16566635
TI  - Ziprasidone-induced acute dystonic reactions in patients with bipolar disorder.

PMID- 16566636
TI  - Monosymptomatic hypochondriacal psychosis or tardive dystonia?

PMID- 16566638
TI  - Small bowel: the last frontier.

PMID- 16566639
TI  - Double-balloon enteroscopy: a descriptive study of 50 explorations.
AB  - AIM: To evaluate the utility of double-balloon enteroscopy for small-bowel
      disease. DESIGN: A prospective study of 50 consecutive enteroscopies performed
      from December 2004 to July 2005 to analyze diagnoses and treatments. PATIENTS: 44
      patients (33 had undergone a previous capsule endoscopy) with indications for
      obscure digestive hemorrhage, angiodysplasia, Peutz-Jeghers syndrome, ulcer,
      suspected Crohn's disease, tumors, and refractory celiac disease. RESULTS: We
      carried out enteroscopy studies in 44 patients by the oral route and, in 6
      additional patients, by both the oral and anal routes. We reached the ileon with
      the oral route in all cases but one (jejunal stenosis), and in 4 cases out of 7
      with the anal route, with an average duration of 73 minutes. We found
      angiodysplasia in 19 cases, as well as NSAID-related enteropathy, Crohn's
      disease, diverticulosis, and Waldenstrom's disease. We performed biopsies in 31%
      of cases with diagnoses of adenocarcinoma, lymphangiectasia secondary to tumor in
      celiac disease, and Whipple's disease. We treated 19 patients with angiodysplasia
      (1 to 20 synchronous lesions) with argon, and 4 patients with polyps using
      polipectomy (sporadic polyps or Peutz-Jeghers syndrome). A retained capsule in
      one patient with stenosis was removed. CONCLUSIONS: Double-balloon enteroscopy is
      a useful and effective technique in the diagnosis and treatment of small
      intestine diseases, thus complementing capsule endoscopy. More studies are needed
      to analyze its impact on the management of this condition.

PMID- 16566640
TI  - Diagnostic yield of 335 push video-enteroscopies.
AB  - BACKGROUND AND OBJECTIVES: The diagnostic yield of push enteroscopy (PE) varies
      widely from 13 to 78% of cases, according to the various series. The aim of this
      retrospective cohort study was to determine the endoscopic and histological yield
      of PE in our health area. PATIENTS AND METHODS: A total of 355 consecutive
      patients (190 males/165 females; mean age 45 years, range 15-89) underwent PE
      over a 6-year period, from 1997 to 2003. PE was performed under sedation and
      without overtube. Small-bowel mucosa biopsies were taken in 199 explorations
      (56%). Clinical indications for PE included: chronic diarrhea (35%), occult
      digestive bleeding (ODB) or iron-deficiency anemia (28%), suspected small-bowel
      malignancy (16%), chronic abdominal pain (28/355; 8%), follow-up of polyposis or
      malabsorption syndromes (7%), and abnormal radiographic findings (6%). RESULTS:
      PE detected lesions in 122 cases (34%); in 6 cases (6%) lesions were within the
      reach of esophagogastroduodenoscopy. A normal macroscopic appearance of the small
      intestinal mucosa with an abnormal histological study was seen in 16 patients
      (6%). Major findings included: malabsorptive diseases (14%), nonspecific
      enteropathy (5%), angiodysplasia (3,5%), lymphangiectasia (3%); jejunal polyps
      (2%), Crohn s disease (2%), intestinal tumors (2%), extrinsic jejunal strictures
      (0.5%), and other (10/355; 3%). Abnormal radiographic findings (62%), chronic
      diarrhea (37%) and ODB (31%) were the indications with a higher diagnostic yield.
      No major complications were seen. CONCLUSIONS: According to our experience, PE is
      a safe and useful tool for the evaluation of small-bowel disease, especially in
      some indications (abnormal radiographic findings, chronic diarrhea, and ODB).
      Small-bowel biopsy increases PE's diagnostic yield in patients with chronic
      diarrhea.

PMID- 16566641
TI  - Polymorphisms in the interleukin-10 gene and relation to phenotype in patients
      with ulcerative colitis.
AB  - BACKGROUND AND OBJECTIVES: Interleukin-10 (IL-10) has a key role in regulating
      mucosal inflammation in inflammatory bowel disease. In our population of Spanish
      ulcerative colitis (UC) patients, we have previously demonstrated that two
      polymorphisms (IL-10.G14 microsatellite allele and homozygous for the -1082G
      allele (guanine at position -1082)) in the IL-10 gene were susceptibility markers
      for disease. No data exist regarding the relationship of these IL-10
      polymorphisms with phenotypic subpopulations in UC. Therefore, this study sought
      to examine the contribution of IL-10 polymorphisms to phenotypical variability in
      UC. MATERIAL AND METHODS: A cohort of 215 Spanish unrelated patients with UC
      recruited in a single center was studied. All patients were rigorously phenotyped
      and followed for at least 3 years (mean time: 11.8 years). The clinical phenotype
      was established before genotyping. Genotyping was performed using polymerase
      chain reaction (PCR) assays. RESULTS: Patients with UC included 129 (60%) men and
      89 (40%) women. Mean age at diagnosis was 38 years, with a range of 8-83. Disease
      extent included 127 (59.1%) left-side patients and 88 (40.9%) extensive patients.
      Neither UC phenotype variable was associated with the presence of susceptibility
      polymorphisms (10G14 microsatellite and -1082G allele). CONCLUSIONS: In Madrid's
      Spanish population of UC patients, the carrying of the ILG14 microsatellite or 
      1082G polymorphism in the IL-10 gene was not associated with phenotype of
      disease.

PMID- 16566642
TI  - Informed consent document in gastrointestinal endoscopy: understanding and
      acceptance by patients.
AB  - OBJECTIVE: We wanted to know if patients read and understand the informed consent
      (IC) document used for endoscopic procedures, and to evaluate the readability of
      IC. METHOD: During two months we gave patients studied in our endoscopy unit an
      anonymous questionnaire with different items concerning reading degree, knowledge
      of the technique, complications, sedation used, and information received. We
      evaluated IC readability using the Flesch index. RESULTS: 309 patients were
      included (mean age: 53 years, 55% males, 86% outpatients, 50% with basic
      education); 85% of patients read the IC, 96% considered they understood the
      exploration technique, 22% were not aware of severe complications, and 82% knew
      which kind of sedation would be used; 88% of patients received additional
      information from their doctors. Outpatients read the IC in a greater percentage
      versus inpatients (p < 0.05); patients with only basic education tended to ignore
      the possibility of complications (p < 0.05). Doctors gave more information to
      rural patients (p = 0.08), offered better information about complications to
      urban patients (p = 0.09), and offered more information on other diagnostic
      procedures to patients older than 50 years (p < 0.05). With the Flesch index we
      found that gastroscopy and colonoscopy ICs had a "standard" level of readability,
      while ERCP ICs were more complex. CONCLUSIONS: The majority of our patients read
      and understands the IC. Doctors adapt information to patient characteristics. Our
      IC documents have an acceptable level of readability, but given that 50% of our
      patients have only a basic educational status, we should attempt to provide an
      easier IC document.

PMID- 16566643
TI  - Hepatitis B surface antigen detection using pooled sera. A cost-benefit analysis.
AB  - OBJECTIVES: To examine the feasibility and to perform a cost benefit analysis of
      a 5-sample pooling strategy using an enzyme immunoassay (EIA) for the screening
      of hepatitis B surface antigen (HBsAg). MATERIAL AND METHODS: To assess the
      sensitivity and specificity of the pooling method, each of the 40 positive sera
      (from weak to intensely HBsAg-positive) and 250 negative sera were tested in a
      pool with 4 HBsAg-negative sera. The limit of detection for HBsAg/ad and HBsAg/ay
      was evaluated using sera from a panel of purified subtypes. A study under real
      conditions was conducted using pools from 340 pregnant women. RESULTS: The
      sensitivity and specificity of this technique were 100%. The correlation
      coefficient among the sample/cutoff ratios of 40 samples studied in single and in
      pooled conditions was 0.792 (p < 0.005). The pooling method has lower levels of
      detection for HBsAg/ad and HBsAg/ay at 0.20 ng/mL and 0.12 ng/mL, and the single
      method at 0.34 ng/mL and 0.29 ng/mL, respectively. The pooling method loses no
      sensitivity for values up to 100 IU/L of anti-HBs in the four sera mixed with a
      positive serum. The cost-benefit analysis showed that the pooling method could
      save from 30% up to 75% of the cost of HBsAg determination, according to whether
      seroprevalences were 10% or 1%, respectively. CONCLUSIONS: The pooled HBsAg EIA
      yielded no worse than the single EIA test, and was a cost-effective and valid
      strategy in areas with a high, medium or low prevalence.

PMID- 16566644
TI  - Current indications of liver biopsy.

PMID- 16566645
TI  - Epiploic appendicitis.

PMID- 16566646
TI  - [Intestinal obstruction caused by colonic tuberculosis. Presentation of two
      cases].

PMID- 16566647
TI  - [Reply to "anal prolapse of a sigmoid lipoma"].

PMID- 16566648
TI  - [Gastric carcinosarcoma].

PMID- 16566649
TI  - [Hepatic metastases: a way of GIST presentation].

PMID- 16566650
TI  - [Glutaraldehyde colitis].

PMID- 16566651
TI  - [Prognostic factors in bacteremia and sepsis].

PMID- 16566652
TI  - [Fever in patients of a Service of Internal Medicine: prospective study in 204
      cases].
AB  - OBJECTIVES: Fever in hospitalized patients (FHP) is a difficult problem. We study
      clinical characteristics and predictive parameters of infection, sepsis and
      outcome. PATIENTS AND METHODS: Prospective study of 204 patients with fever > 38
      degrees C admitted in an Internal Medicine ward. In each patient clinical
      evaluation, complete blood count (CBC) urinalysis (UA), C-reactive protein (CRP),
      chest X- ray (CXR), blood and urine cultures were performed. RESULTS: 115
      patients suffered infection (75.9% nosocomial, 7.4% sepsis), 35 had a non
      infectious etiology and 54 an unknown cause. CBC and CRP did not distinguish
      infection, bacteremia or sepsis. In UA, positive nitrites, leukocytes and
      bacteriuria were predictive of infection. 18.6% of the patients were diagnosed by
      CXR. 18% of urine cultures and 13% of blood cultures were positive. 71.6%
      received antibiotics (deemed unnecessary in 18%). Microbiological results
      modified 25% of initial treatments. Average hospital stay was 17 days; 16.7%
      died. Chronic lung disease, fever duration, dysphagia and urinary tract
      alterations predict infection. Obesity, diabetes mellitus, liver failure,
      immunocompromised host, central vascular access, fever duration and nosocomial
      infection predict bacteremia. Sepsis is more prevalent in males, with malignancy
      and vascular or nosocomial infection. Chronic liver disease, nosocomial
      infection, severe lung infection and sepsis increase mortality. CONCLUSIONS:
      Clinical diagnosis of FHP is inaccurate. Infection is it s most frequent cause;
      UA, CXR, and blood and urine cultures are useful. FHP increases mortality and
      hospital stay. We have established predictable models of infection, bacteremia,
      sepsis and mortality. However, its sensibility and specificity are low.

PMID- 16566653
TI  - [Epidemiological features of community- and nosocomial-acquired bacteremia in the
      hospitalized elderly patients].
AB  - OBJECTIVES: To analyze the epidemiology and to identify associated factors for
      community- and nosocomial-acquired bacteremia in the elderly (BE). PATIENT AND
      METHODS: Elderly patients diagnosed of bacteremia were selected. Community- or
      acquired-bacteremia were defined according to standard criteria. The severity of
      underlying diseases was classified as non-fatal, ultimately fatal, or rapidly
      fatal, according to McCabe-Jackson criteria. Multivariate analysis by logistic
      regression was used to identify associated factors to bacteremia. RESULTS: Two
      hundred and forty-two cases of BE were selected. The mean age was 72.5 years, 50%
      occurred in males. One hundred and thirty cases (53.7%) were community-acquired
      and 112 (46.3%) cases were nosocomial-acquired BE. Most common underlying
      diseases were diabetes mellitus (30.6%%), chronic obstructive pulmonary disease
      (25.6%) and neoplasia (24%). Gram-negative bacteria were more frequently isolated
      in community-acquired BE, while gram-positive cocci were more common in
      nosocomial-acquired BE. Sources of infection were: vascular (19%), respiratory
      tract (18.6%), biliary tract (17.8%) and urinary tract (8.3%). The factors
      associated with nosocomial-acquired BE were (adjusted OR; 95%CI): underlying
      diseases (5.4; 2.7-10.8), neoplasia (2.5; 1.3-4.9) and vascular origin (2.2; 1.1
      4.5). Fifty-two patients died (23.1%). CONCLUSIONS: BE occurs in elderly patients
      debilitated with well-defined underlying diseases. BE is associated to high
      mortality.

PMID- 16566654
TI  - [Mortality and prognostic factors in patients admitted with community-acquired
      bacteremia].
AB  - BACKGROUND: Community-acquired bacteremia is a frequently clinical problem and is
      associated with a high mortality. The Pitt bacteremia score that is calculated
      using body temperature, mental status, and some respiratory and circulatory
      features is an useful tool in order to know the prognosis of patients with
      bacteremia. Objectives were to know microbial etiology of bacteremia in our
      community, percentage of patients that received an inadequate empiric antibiotic
      treatment and independent prognostic factors associated with mortality, including
      Pitt bacteremia score. METHOD: Observational study of a cohort of patients over
      18 years admitted at a tertiary hospital due to an infection with a community
      acquired bacteremia. Twenty-eight cases were rejected because possible blood
      culture contamination. RESULTS: Seventy-five patients were included, the mean age
      was 68.6 +/- 18.2 years, 38 women (51%). Mortality rate was 23% [IC95% 13.8
      33.8]. More frequent bacteria isolated were Escherichia coli, Staphylococcus
      aureus, coagulase negative staphylococci, Pseudomonas aeruginosa, Streptococcus
      viridans, enterococci and Klebsiella spp. Mortality in patients treated with an
      inadequate antibiotic therapy (18%, 3 patients) was not lower than in adequately
      treated patients (24%, 14 patients, p = 0.42). Independent prognostic factors
      related to mortality were serum albumin concentration, OR = 5.17 (IC 95% 1.45
      16.7) for every downing step of 1 g/dl, the Pitt bacteremia score OR = 1.50 (IC
      95% 1.01-2.24) for every unit increase, and a high score at McCabe and Jackson
      classification OR = 5.08 ( IC 95% 1.43-16.7). CONCLUSIONS: An inadequate empiric
      antibiotic therapy was not associated with a worse vital prognosis. Independent
      prognostic factors related to mortality were serum albumin concentration, the
      Pitt bacteremia score, and the McCabe and Jackson classification.

PMID- 16566656
TI  - [Bacteraemia due to Leuconostoc spp. in a patient without immunological
      disorders].
AB  - Leuconostoc spp are gram-positive coccobacilli, catalase and oxidase negative,
      vancomycin resistant. Causes of infection have been reported previously but it
      has not been described confirmed bacteremia due to Leuconostoc spp in patient
      without other immunological disorders. We describe a case of bacteremia in a 64
      years-old man with a prosthetic valve 7 months before to begin fever of unknown
      origin. We confirmed bacteremia due Leuconostoc spp and the treatment with
      respective antibiotics permits the cure. Leuconostoc spp should be considered as
      a potential cause of bacteraemia, but we would be observant to the bacteremias
      due vancomycin resistant germs, because in most cases the laboratory do not find
      the sensitivity to this antibiotic.

PMID- 16566655
TI  - [Pulmonary Langerhans'-cell histiocytosis].
AB  - Pulmonary Langerhans'-cell histiocytosis belongs to a spectrum of diseases
      characterized by monoclonal proliferation and infiltration of organs by
      Langerhans' cells. It is an uncommon interstitial lung disease of unknown
      etiology occurring almost exclusively in cigarette smokers. It s course in adults
      is variable and unpredictable, ranging from benign self-limiting types with
      spontaneous regression to slowly progressive malignant disease that leads to
      respiratory failure and death. We report one patient diagnoses of pulmonary
      Langerhans' cell histiocytosis who experimented an objective radiographic
      improvement and disappearance of symptoms after smoking cessation.

PMID- 16566657
TI  - [Pericardial effusion as the only first clinical manifestation of systemic lupus
      erythematosus].
AB  - Pericarditis is the most frequent cardiac manifestation of systemic lupus
      erythematosus (SLE), but pericardial effusion rarely occurs as the only first
      clinical manifestation of SLE. We report the case of a male patient whose initial
      manifestation of lupus was a pericardial effusion. We comment on its clinical
      course and we reviewed in the medical literature different presenting features in
      SLE.

PMID- 16566658
TI  - [Carcinoma of the Fallopian tube: a case].
AB  - The case of a 43-years old woman with previous history of mental retardation and
      major depressive syndrome, consulting for metrorrhagia is presented. At physical
      examination a right adnexal mass was detected on palpation. Transvaginal
      echography showed a 3-cavity cyst in right ovary. A surgical intervention with
      total hysterectomy and dual adnexectomy was performed. Pathological study showed
      proliferative endometrium, bilateral follicular cysts and well differentiated
      serous adenocarcinoma located at fallopian tube. The patient refused adjuvant
      chemotherapy, a close follow-up is ongoing in outpatient Oncology Unit. Then some
      epidemiologic, etiologic, clinica, diagnostic and therapeutic issues related to
      this rare tumour are discussed.

PMID- 16566659
TI  - [Tumor necrosis factor blocking agents: a review. Part II: safety and
      recommendations].
AB  - Blockade of tumor necrosis factor with monoclonal antibodies, has emerged as one
      of the most promising therapies in some autoimmune conditions as rheumatoid
      arthritis, ankylosing spondylitis, psoriatic arthritis and Crohn's disease. They
      have shown effectiveness on reducing symptoms and modifying the progression of
      the disease. However, they disrupt the balance of inflammatory and immune
      responses and some risks associated with TNF-blockers have become apparent. The
      purpose of this article is to review the evidence about benefits and risk
      associated with the use of TNF-blockers in approved indications and to provide
      practical recommendations for its use in the management of this conditions.

PMID- 16566660
TI  - [Multiple primary synchronous neoplasm of the lung].

PMID- 16566664
TI  - Three-phase hand acupuncture: a new discovery inspired by the auricular
      acupuncture microsystem.

PMID- 16566661
TI  - Developing a musculo-skeletal screening survey for Indigenous Australians living
      in rural communities.
AB  - INTRODUCTION: Indigenous Australians living in rural communities experience high
      levels of musculoskeletal conditions that significantly impair their daily
      activities. Aboriginal health workers (AHWs) have a close understanding of their
      communities' needs and play a central role in the assessment and management of
      these conditions. To assist in the musculoskeletal assessment process a screening
      survey was collaboratively developed, trialled and evaluated for use by AHWs.
      METHODS: A cross-sectional survey was developed following discussions with key
      community informants, and a literature review for relevant survey instruments. It
      was piloted before being administered by AHWs and the findings compared with
      those of a clinical assessment conducted by musculoskeletal health professionals.
      The participants included 189 members of an Australian rural Indigenous
      community. RESULTS: The screening survey achieved face and content validity. It
      provided high sensitivity (above 70%) and moderately high specificity (above 60%)
      for measuring musculoskeletal conditions in this community. It did not achieve
      high enough Kappa scores when measuring agreement between the screening tool and
      clinical assessment. A significant correlation was, however, obtained between the
      most prevalent musculoskeletal condition and between reported overall pain as
      assessed by AHWs and chiropractors. CONCLUSIONS: The screening survey has
      applicability in this community and has the potential to be adapted in similar
      settings. Incorporating a basic range of motion and palpation assessment to
      localise painful anatomical sites may help to further improve the sensitivity and
      specificity of this instrument.

PMID- 16566665
TI  - Observational study on homeopathic treatment.

PMID- 16566666
TI  - Methodological difficulties in homeopathic treatment of children with ADD/ADHD.

PMID- 16566667
TI  - Weak quantum theory: satisfied by quantized critical point fluctuations.

PMID- 16566668
TI  - Standardization of individualized treatments in a randomized controlled trial of
      acupuncture for stroke rehabilitation.

PMID- 16566669
TI  - Reactive oxygen species--(ROS) pathogens or sources of vital energy? Part 1. ROS
      in normal and pathologic physiology of living systems.
AB  - Free radicals and reactive oxygen species (ROS) are considered to be dangerous
      pathogens as they may damage key molecular constituents of cells. However this
      concept approach does not take into account vital functions of ROS in normal
      physiology. Information has emerged that a substantial share of oxygen consumed
      by aerobic organisms is used for ROS production and that ROS are indispensable
      for regulation of multiple functions of living cells. Yet, each cell is equipped
      with powerful means to eliminate ROS immediately. Explanations of the mechanisms
      of regulatory action of ROS upon a wide spectrum of biochemical and physiologic
      reactions and of ROS therapeutic efficacy raise serious problems in the framework
      of the conventional biochemical paradigm. Here data concerning ROS production and
      utilization are considered with an emphasis on an apparent paradox: Why does the
      body produce a lot of ROS and then eliminate them as soon as they appear?

PMID- 16566670
TI  - Quantum events of biophoton emission associated with complementary and
      alternative medicine therapies: a descriptive pilot study.
AB  - INTRODUCTION: Biophoton emission (BPE) is a quantum event characterized by a
      relatively stable but ultralow- rate emission of visible photons from living
      organisms. It has been associated with high energy processes such as: cell
      metabolism, growth, phagocytosis, neural activity, and oxidative stress. BPE has
      also been suggested to reflect the organism's global state of health as well as
      the response to stimulation including therapeutic interventions. If BPE changes
      occur as a result of various complementary and alternative medical interventions,
      this could prove useful to monitor both the patient's response to a specific
      treatment and global changes in their health status. This descriptive study
      attempts to identify BPE changes associated with three different chiropractic
      techniques that use different energetic approaches: mechanical, gravitational,
      and bioenergetic. MATERIALS AND METHODS: The BPE was measured at the neck and/or
      the lower back of 3 asymptomatic adult male volunteers. The measurements were
      made before and after different chiropractic interventions. The treatment
      techniques included a high velocity joint manipulation with the aid of a drop
      table, Sacro-Occipital Technique, and Bio-Energetic Synchronization Technique.
      Enough time was allotted for measurements in order to differentiate between
      natural fluctuation of the BPE and the changes induced by the interventions.
      RESULTS: All techniques induced small (up to 20%) but statistically significant
      changes (p < 0.05 in one case, p < 0.001 in the other two) in the BPE. Each
      technique demonstrated a different pattern of BPE change that may be specific to
      the technique. CONCLUSION: The intensity of BPE is a noninvasive indicator of the
      health of the human body and is significantly altered in different ways by
      chiropractic interventions. Future research is necessary to explore more features
      of BPE and its utility as an indicator of health, as well as the theoretical and
      clinical significance of these findings.

PMID- 16566671
TI  - Inhibition of growth and induction of apoptosis in human cancer cell lines by an
      ethyl acetate fraction from shiitake mushrooms.
AB  - OBJECTIVE: Shiitake (Lentinus edodes) mushrooms have been reported to have cancer
      preventing properties. However, little research has been conducted verifying the
      antitumor activities of "mycochemicals" in shiitake mushrooms. In this study,
      potential roles of an ethyl acetate fraction from shiitake mushrooms were
      investigated by in vitro bioassays. DESIGN: The activities of an ethyl acetate
      fraction were evaluated by [3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium
      bromide] (MTT), apoptosis bioassay, cell cycle analysis, and Western blot
      analysis using two human breast carcinoma cell lines (MDA-MB-453 and MCF-7), one
      human nonmalignant breast epithelial cell line (MCF-10F), and two myeloma cell
      lines (RPMI-8226 and IM-9). RESULTS: Concentration-dependent antiproliferative
      effects of the fraction were observed in all cell lines using the MTT assay.
      Approximately 50 mg/L concentration of the fraction induced apoptosis in 50% of
      the population of four human tumor cell lines and the fraction-induced apoptosis
      may have been mediated through the pro-apoptotic bax protein which was up
      regulated. Cell cycle analysis revealed that the fraction induced cell cycle
      arrest by significant decrease of S phase, which was associated with the
      induction of cdk inhibitors p21 and the suppression of cdk4 and cyclin D1
      activity. Compared to malignant tumor cells, nonmalignant cells were less
      sensitive to the fraction for the suppression of cell growth and regulation of
      bax, p21, cyclin D1, and cdk4 expression. A 51% antiproliferative effect occurred
      at the highest concentration of the fraction (800 mg/L). CONCLUSIONS: These data
      suggest that inhibition of growth in tumor cells by "mycochemicals" in shiitake
      mushrooms may result from induction of apoptosis.

PMID- 16566673
TI  - Integrative care and bridge building among health care providers in Norway and
      Denmark.
AB  - BACKGROUND: Patients in Norway and Demmark with the medical diagnoses of cancer,
      multiple sclerosis (MS), and HIV/AIDS use complementary and alternative treatment
      (CAT) in growing numbers, most often in addition to receiving conventional
      treatment. At the same time, the interest and demand from patients for more
      holistic-oriented care is strongly increasing. Following this, there is a desire
      and need for better communication and cooperation among the conventional medical
      establishment, CAT practitioners, and patients. This development raises new
      demands on research designs to incorporate complexity and diversity concerning
      the intervention, effect mechanisms, and outcomes. DISCUSSION: This article
      outlines different models used to combine conventional, complementary, and
      alternative treatment (CCAT), describing various degrees of integration among
      therapies. The authors are closely involved in three current and planned research
      projects in Norway and Denmark focusing on cancer, MS, and HIV/AIDS. These
      research projects are briefly introduced as examples of bridge-building efforts
      dealing with integrative care. Despite explicit political good will in Norway and
      Denmark, initiatives to enhance integration face challenges connected to lack of
      knowledge; resistance toward CCAT; lack of time, space, and economic resources;
      and patients left without any claim on insurance in the case of treatment
      failure. These challenges are outlined based on the researchers' experience from
      being involved in the research projects. CONCLUSIONS: To optimize treatment
      outcomes in the future, it is argued that the need for closer cooperation among
      conventional and alternative therapists across professional boundaries in an
      interactive partnership with patients is evident. Researchers have to rethink
      research design and methods in meeting the new trend toward bridge building based
      on integrative health care.

PMID- 16566672
TI  - The chemical and biologic profile of a red clover (Trifolium pratense L.) phase
      II clinical extract.
AB  - OBJECTIVES: To document the chemical and biologic profile of a clinical phase II
      red clover (Trifolium pratense L.) extract by identifying and measuring the major
      and minor components visible in the high-performance liquid chromatography
      ultraviolet (HPLC-UV) chromatogram and evaluating each compound for estrogenic
      and antioxidant activity. DESIGN: Individual compounds in the preformulated
      (i.e., no excipients present) extract were identified by either chemical
      isolation followed by structure elucidation or matching to retention time and
      molecular mass of chemical standards via liquid chromatography-mass spectrometry
      (LC-MS) analysis. Quantitation of the amounts of compounds found in the
      preformulated extract was done using HPLC-UV or LC-MS. Isolated compounds or
      standards were evaluated for their ability to: (1) induce alkaline phosphatase
      (AP) in an endometrial carcinoma cell line, (2) competitively bind to recombinant
      human estrogen receptors (ERs) alpha (alpha) and beta (beta), and (3) act as
      antioxidants by scavenging 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH)
      free radicals. RESULTS: The preformulated red clover extract had 50% effective
      concentration (EC 50) of 2.0 to 2.2 microg/mL in the AP estrogenicity assay, and
      50% inhibitory concentrations (IC(50)s) of 18.4 to 32.6 microg/mL and 1.9 to 3.4
      microg/mL in the ERalpha and ERbeta binding assays, respectively. The
      preformulated extract was composed of 35.54% isoflavones, 1.11% flavonoids, 0.06%
      pterocarpans, < or =0.03% coumarins, and < or =0.03% tyramine. Daidzein,
      genistein, formononetin, biochanin A, coumestrol, and naringenin were estrogenic
      in the AP assay, and all of these, except formononetin, bound to one or both ERs.
      CONCLUSIONS: The major and minor chemical and active estrogenic components of a
      preformulated phase II red clover clinical extract were identified,
      quantitatively measured, and the final capsule doses were calculated. The extract
      is currently under evaluation in a year-long clinical study for the alleviation
      of menopausal hot flashes. This is the first report to thoroughly summarize the
      chemistry and biology of all major peaks observed in the HPLC-UV chromatogram of
      a clinical red clover dietary supplement.

PMID- 16566674
TI  - Comparing effects of auricular acupressure with and without an internet-assisted
      program on smoking cessation and self-efficacy of adolescents.
AB  - OBJECTIVES: This study aimed to develop an Internet-assisted smoking cessation
      program accompanied with auricular acupressure, and compare the quit rate and
      self-efficacy of youth smokers receiving auricular acupressure with and without
      the Internet-assisted smoking cessation program. DESIGN: A Website was
      constructed on IBM Websphere 5.0 and DB2 database using HTML, Javascript, and
      JSP. A quasiexperimental research design was adopted. Subjects were assigned
      nonrandomly to two groups. Group 1 received auricular acupressure plus the
      Internet-assisted smoking cessation program, whereas group 2 received auricular
      acupressure only. MEASUREMENTS: The data of demographic factors, serum cotinine,
      quitting rate, nicotine dependence, and self-efficacy of subjects were collected
      before and after a 4-week intervention. RESULTS: After intervention, the quit
      rate was 15.78% in group 1 and 2.56% in group 2. Nicotine dependence was
      significantly lowered in group 1, but remained unchanged in group 2. The
      improvement of self-efficacy between groups 1 and 2 was significantly different.
      CONCLUSIONS: The combination of auricular acupressure and Internet-assisted
      smoking cessation program was more efficacious than auricular acupressure alone
      in terms of quit rate.

PMID- 16566675
TI  - Efficacy of COLD-fX in the prevention of respiratory symptoms in community
      dwelling adults: a randomized, double-blinded, placebo controlled trial.
AB  - BACKGROUND: COLD-fX (CVT-E002), a proprietary extract of the roots of North
      American ginseng (Panax quinquefolium), rich in poly-furanosyl-pyranosyl
      saccharides, has been found efficacious in the prevention of respiratory
      infections in institutionalized seniors and healthy adults. OBJECTIVE: We
      examined the efficacy of COLD-fX in the prevention of acute respiratory illness
      (ARI) in community dwelling seniors. DESIGN: This was a randomized, double-blind,
      placebo controlled trial. INTERVENTION: The participants were asked to take 2
      capsules/day of either COLD-fX or placebo (200 mg/ capsule) for a period of 4
      months. SUBJECTS: A total of 43 community-dwelling adults aged 65 years or older
      were recruited. Following one month of intervention, subjects were immunized with
      influenza vaccine. OUTCOME MEASURES: Subjects recorded the incidence and duration
      of respiratory symptoms during the study. They also recorded the incidence of
      adverse events during the study. RESULTS: The frequency and duration of ARI
      during the first two months of the study was found to be similar in the two
      groups. However, during the last 2 months (November and December) significantly
      fewer subjects in the COLD-fX group 32% reported ARI compared to the placebo
      group 62%. The duration of symptoms during the last 2 months was significantly
      shorter in the COLD-fX group than the placebo group (5.6 days in the COLD-fX
      group vs 12.6 days in the placebo group). There was no influenza illness
      circulating in the community during the period of the study. CONCLUSIONS:
      Ingestion of COLD-fX by immunocompetent seniors during an early "cold and flu"
      season reduced the relative risk and duration of respiratory symptoms by 48% and
      55%, respectively. Daily COLD-fX administration can thus be a safe, natural
      therapeutic means for the prevention of ARI in healthy seniors.

PMID- 16566676
TI  - A systematic review of Chinese medicinal herbs for acute bronchitis.
AB  - OBJECTIVES: To assess the effectiveness and safety of Chinese medicinal herbs for
      treating uncomplicated acute bronchitis. DATA SOURCES: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL), which includes the Cochrane
      Acute Respiratory Infections Group's specialized register; The Chinese Cochrane
      Centre's Controlled Trials Register; MEDLINE; EMBASE; and the Chinese Biomedical
      Database (CBM). METHODS: We only included randomized controlled trials. At least
      two authors extracted data and assessed trial quality. MAIN RESULTS: Four trials
      reported the time to improvement of cough, fever, and rales associated with
      bronchitis and showed that patients treated with Chinese herbs had a shorter
      duration of signs and symptoms. Two trials reported the proportion of patients
      with improved signs and symptoms at follow-up and showed that Chinese herbs were
      beneficial in terms of relief of signs and symptoms. Thirteen (13) trials
      analyzed the data on physician global assessment of improvement at follow-up.
      Nine (9) of 13 trials showed that Chinese herbs were superior to routine
      treatment and the other four trials showed a similar effect to routine treatment.
      In general, Chinese herbs appeared beneficial. Only one trial reported adverse
      effects during treatment. CONCLUSIONS: There are insufficient quality data to
      recommend the routine use of Chinese herbs for acute bronchitis. The benefit
      found in this systematic review could be due to publication bias and study-design
      limitations of the individual studies. In addition, the safety of Chinese herbs
      is unknown due to the lack of toxicological evidence on these Chinese herbs,
      though adverse events are rarely reported.

PMID- 16566677
TI  - Chinese medicinal herbs for influenza: a systematic review.
AB  - BACKGROUND: Influenza is an acute respiratory communicable disease which can
      cause high morbidity and mortality in an epidemic. Traditional Chinese medicinal
      herbs following a particular theory may be a potential medicine of choice.
      OBJECTIVES: We aim to assess the therapeutic effect and adverse reaction of
      traditional Chinese medicinal herbs in the treatment of uncomplicated influenza.
      SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE, CBM, and
      handsearched the relevant Chinese journals. SELECTION CRITERIA: Randomised and
      quasi-randomised trials compared with placebo, or with other chemical drugs
      normally used in care, or various other Chinese medicinal herbs amd chemical
      drugs with herbal preparations compared with simple chemical drugs were also
      included. DATA COLLECTION AND ANALYSIS: At least two reviewers extracted data and
      assessed trial quality. MAIN RESULTS: We included 8 relevant studies, most of
      which were of low quality. Because of the clinical heterogeneity, we did not
      perform a summary meta-analysis. Some of the studies showed positive results
      favouring Traditional Chinese medicinal herb treatment compared to antiviral or
      antipyretic-analgesic drugs or the combination of them. Only three studies
      mentioned adverse reactions but no detailed data were acquired in the included
      studies. REVIEWERS' CONCLUSIONS: The small number of included studies and
      participants, as well as the low quality of most studies, made the evidence far
      from conclusive for clinical decision making. More high quality randomised
      controlled trials (RCTs) with similar interventions are required to strengthen
      the evidence for the efficacy and safety of certain herbal preparations.

PMID- 16566678
TI  - Is quality control of Cochrane reviews in controversial areas sufficient?
AB  - OBJECTIVES: Some conclusions from the Cochrane Database of Systematic Reviews
      (CDSR) seem volatile in areas of controversy and have recently changed
      conclusions. With this perspective in mind we decided to test the validity and
      sensitivity of negative conclusions in a systematic review of low-level laser
      therapy (LLLT) for osteoarthritis (OA) from the Cochrane Library was valid and
      robust. SETTINGS/LOCATION: None as this was a systematic review of literature.
      DESIGN: Validity was tested against a 9-item checklist for systematic reviews.
      Review selections were analyzed for possible discrepancies between trial and
      review reports and omissions of relevant trials and data. Data from discrepancies
      and omissions were then entered into sensitivity and subgroup analyses. OUTCOME
      MEASURES: Continuous and dichotomous data for pain SUBJECTS: Patients with
      osteoarthritis. INTERVENTIONS: LLLT. RESULTS: Only clinicians who had performed
      LLLT trials, and had negative results were invited into the review group. The
      review was oblivious to findings published after 1993 about physiologic
      mechanisms and dose response patterns for LLLT. We found 18 questionable
      selections that favored a negative review conclusion in 17 of 18 cases. These
      were largely omissions of relevant positive data and selective inclusion of
      negative data from trials with small, ineffective doses. When existing and
      omitted data from relevant trials were combined, results changed from negative to
      significantly positive for continuous and categorical data. Subgrouping trials by
      location and recommended doses taken from current guidelines, revealed a highly
      significant effect of LLLT for treating knee OA. CONCLUSIONS: The results of this
      CDSR was not robust and seems to be colored by questionable selections or
      omissions. For alternative pain therapies, it should be considered if lack of
      expertise on therapy mechanisms, or conflicts of interests with competing pain
      drug manufacturers, may bias conclusions. Review groups should recruit a balanced
      mix of current views and expertise and expand the use of sensitivity analyses to
      improve quality of CDSRs in areas of controversy.

PMID- 16566679
TI  - Strengths, weaknesses, and development of Traditional Chinese Medicine in the
      health system of Hong Kong: through the eyes of future Western doctors.
AB  - Five focus group discussions were conducted with 28 (fourth-year) medical
      students from the Chinese University of Hong Kong (CUHK) to explore attitudes to
      Traditional Chinese Medicine (TCM) and its impact on the future of medical
      training. Most students perceived that TCM was a good alternative for certain
      health problems but lack of scientific evidence and the absence of regulation
      were major barriers. Students were concerned about the limitations of TCM, but
      identified their need to understand TCM to effectively communicate with their
      patients. Paralleled with the experience in the United Kingdom and other
      countries, if traditional and conventional doctors are to work effectively side
      by side, current medical education and health service arrangements need to
      change.

PMID- 16566688
TI  - Resuscitation fluid controversies--Australian trials offer new insights.

PMID- 16566681
TI  - Producing and disseminating systematic reviews: a summary of the CAM-related work
      presented at the 13th international Cochrane Colloquium.
AB  - In order to facilitate the conduct and dissemination of high-quality systematic
      reviews in CAM further, three key issues were discussed at the Melbourne Cochrane
      Colloquium: (a) How to improve the overall methodological quality of CAM reviews
      in general, (b) how to improve the quality of Traditional Chinese Medicine
      reviews and trials; and (c) how to make the CAM reviews more accessible to the
      lay public throughout the world. A summary of each of these is presented.

PMID- 16566689
TI  - "... the occasion fleeting; experience fallacious, and judgement difficult.".

PMID- 16566690
TI  - Advanced haemodynamic monitoring: getting to the heart of it.

PMID- 16566692
TI  - MET: the emergency medical team or the medical education team?

PMID- 16566691
TI  - Is there an ideal insulin adjustment protocol for the critically ill patient?

PMID- 16566693
TI  - Safety and feasibility of an insulin adjustment protocol to maintain blood
      glucose concentrations within a narrow range in critically ill patients in an
      Australian level III adult intensive care unit.
AB  - OBJECTIVE: Recent data have shown a link between normal blood glucose levels and
      improved outcomes in intensive care patients. We wished to develop an insulin
      adjustment protocol for an adult intensive care unit to maintain blood glucose
      concentrations safely within a narrow range. METHODS: After a 6 month
      introductory period, an observational study was conducted during a 10 month
      period in an Australian level III intensive care unit to assess the safety and
      feasibility of an insulin adjustment protocol to maintain blood glucose
      concentrations safely within a narrow range. The protocol included a variable
      insulin infusion, a constant caloric source and frequent blood glucose level
      monitoring to detect and prevent hypoglycaemia. RESULTS: Over the 10 month period
      a total of 148 patients were studied using the protocol and represented 13 % of
      all intensive care unit admissions during this period. In total, there were
      12,623 patient hours 'on protocol', with 5,603 blood glucose levels performed.
      The mean morning blood glucose level was 6.5 mmol/L and 49% of blood glucose
      levels were within the target range of 4.1 - 7.0 mmol/L. There were four recorded
      incidents of hypoglycaemia, defined as a blood glucose level of less than 2.2
      mmol/L, the lowest at 1.5 mmol/L being the only symptomatic episode. The
      incidence of hyperglycaemia (blood glucose level > 10 mmol/L) was 13 % of all
      blood glucose level measurements. CONCLUSIONS: The insulin adjustment protocol
      with a constant caloric source and frequent blood glucose level monitoring was
      found to be safe and feasible in maintaining blood glucose concentrations within
      a narrow range in a mixed adult intensive care unit population.

PMID- 16566694
TI  - Failure of continuous cardiac output measurement using the PiCCO Device during
      induced hypothermia: a case report.
AB  - Continuous cardiac output measurement using pulse contour analysis is a technique
      gaining widespread acceptance in intensive care units. We report a case where a
      pulse contour analysis computer (PiCCO, Pulsion Medical Systems, Munich, Germany)
      failed to calibrate in a patient who was undergoing induced hypothermia for
      anoxic brain injury. Despite several attempts to calibrate, using increased cold
      injectate volumes and exchanging both the PiCCO device and the arterial catheter,
      we were unable to correct the calibration problem and hence were unable to
      monitor cardiac output. Subsequent rewarming of the patient allowed calibration
      of the arterial waveform and continuous cardiac output measurement. We were
      unable to find any previous reports of this problem using a PiCCO device,
      although similar problems with thermodilution cardiac output estimation using the
      pulmonary artery catheter during hypothermic cardiopulmonary bypass have been
      documented.

PMID- 16566695
TI  - Traumatic liver injury complicating cardio-pulmonary resuscitation. The value of
      a major intensive care facility: a report of two cases.
AB  - Complications associated with external cardiac compression include trauma to the
      heart, chest wall, lungs and gastrointestinal viscera, with gastrointestinal
      visceral injury including, ruptured stomach, liver, oesophagus, spleen and colon.
      However, the use of thrombolytics and anticoagulants in patients with an acute
      myocardial infarction increases the incidence of a visceral haemorrhage when
      these patients need cardiopulmonary resuscitation. We report two out-of-hospital
      cardiac arrest patients whose immediate post-resuscitation phase was complicated
      by hepatic injury and significant haemoperitoneum. Conservative management in a
      major intensive care unit of both the liver trauma and the induced coagulopathy
      was associated with a successful outcome in both cases.

PMID- 16566696
TI  - Acute hepatic failure caused by an acute aortic dissection with cardiac
      tamponade: a case report.
AB  - An acute cardiac tamponade from any cause may result in rapid deterioration of
      hepatic function in a previously healthy patient. We describe a case of an acute
      ascending aortic dissection that presented as acute hepatic failure, due to an
      acute cardiac tamponade and severe right heart failure. The differential
      diagnosis of the aetiology of acute liver failure is extensive and includes
      poisonings, vascular obstruction and sepsis, particularly on the background of
      decompensated liver disease. Many of these conditions are associated with
      hypotension. The acute presentation in our patient, combined with the lack of a
      characteristic history delayed the diagnosis of a proximal (type A) dissection
      with tamponade and subsequent hepatic failure. Severe right-sided heart failure
      as a result of conditions such as cardiac tamponade should be excluded in
      patients presenting with acute hepatic failure of unknown aetiology.

PMID- 16566697
TI  - Levosimendan following coronary artery bypass grafting in a patient with end
      stage renal failure: a case report.
AB  - Levosimendan is a novel inotropic agent indicated for patients with decompensated
      heart failure. It has well recognised mechanisms of action. Its use however, has
      not been described in patients with end-stage renal failure. This report
      describes the use of levosimendan in a post-operative coronary artery bypass
      graft patient with decompensated heart failure and end-stage renal failure
      previously receiving dialysis six days per week. Levosimendan proved to be a safe
      and useful agent when used as a continuous intravenous infusion initially at 0.05
      microg/kg/min then increasing up to 0.2 microg/kg/min for a total of 42 hours.

PMID- 16566698
TI  - The use of the oesophageal Doppler monitor in the intensive care unit.
AB  - OBJECTIVE: To review the theory and clinical use of the oesophageal Doppler
      monitor (ODM) in the intensive care setting. DATA SOURCES: A literature search
      using the key-words in both Medline and Pubmed databases. Information concerning
      insertion techniques and various waveforms was also obtained from the
      manufacturers. SUMMARY OF REVIEW: Both clinical and non clinical means of
      assessing the cardiac output have inherent inaccuracies. Some methods (e.g. the
      pulmonary artery catheter) are associated with potentially life-threatening
      complications. The oesophageal Doppler monitor offers a less-invasive, real-time
      indicator of cardiac output. This review describes the theory of the ODM, the
      technique for its insertion, the waveforms seen in various pathological states
      and appraises the available literature on its use. CONCLUSIONS: The ODM offers a
      minimally invasive means of continuous haemodynamic monitoring with an extremely
      low incidence of complications. It is easy to insert and has been validated
      against established methods of cardiac output monitoring. However, whilst it has
      been shown to be of particular benefit in guiding fluid management and peri
      operative care, there is less evidence of its usefulness in guiding inotrope
      requirements. Additionally, any reduction in morbidity and resource consumption
      has not yet been reported to be associated with an improvement in ICU survival.

PMID- 16566700
TI  - A farewell to P-values.

PMID- 16566699
TI  - Assessment of adrenocortical function in the critically ill.
AB  - OBJECTIVE: To review current concepts in the diagnosis of adrenocortical disease
      in the critically ill patient. DATA SOURCES: A review of articles reported on
      adrenocortical insufficiency in the acutely ill patient. SUMMARY OF REVIEW: The
      contribution of adrenal insufficiency to the morbidity of critically ill patients
      is currently under renewed scrutiny. The debate continues about the role of
      steroids in sepsis and essentially the question remains unanswered. Central to
      this debate is the issue of whether adrenal insufficiency is common in the
      critically ill patient. What is incontrovertible is that adrenocortical function
      is essential for host survival during critical illness, but what constitutes
      adrenocortical insufficiency in critically ill patients is not clear. Absolute
      adrenocortical insufficiency (diagnosed by very low plasma cortisol
      concentrations) is uncommon in the intensive care population. The diagnosis of
      relative adrenocortical insufficiency (elevated basal plasma cortisol with a
      subnormal increase in plasma concentrations following an ACTH stimulus) continues
      to generate debate. The controversy surrounding the role of steroids in sepsis
      and the confusion over the criteria for diagnosing adrenal insufficiency in the
      critically ill are reviewed. CONCLUSIONS: We suggest that the following caveats
      be borne in mind when diagnosing adrenal insufficiency in the critically ill
      patient. Firstly, the gold standard for the diagnosis has not been established.
      Secondly, caution must be exercised when interpreting a single plasma cortisol
      value. In the event of a single result indicating adrenal hypofunction, we
      suggest repeating the measurements after a 6 to 12 hour interval. The clinician
      must also be aware of variations in cortisol concentrations induced by the assay.
      Thirdly, the clinician must be aware of the potential limitations of the
      conventional high dose corticotrophin test. We also suggest that plasma free
      cortisol is more relevant than total plasma cortisol in the assessment of adrenal
      function in critical illness and that the low dose corticotrophin test is more
      sensitive than the conventional high dose test. These areas should be the subject
      of further investigations.

PMID- 16566701
TI  - A 38-year-old morbidly obese man with chest pain, shortness of breath and a numb
      lip.

PMID- 16566702
TI  - "While we often manage dying patients, dying is not an indication for admission
      to an ICU".

PMID- 16566703
TI  - Equivalence trials and the treatment of fungal infections and mortality and other
      event rates: corrections.

PMID- 16566704
TI  - Alternative propellant aerosol delivery systems.
AB  - The year 2006 represents the 50th anniversary of the pressurized metered dose
      inhaler. With most technologies, 50 years represents a significant time span for
      technology evolution and modification, but with propellant-driven metered dose
      inhalers, the pace of change has been relatively slow. We are now in the era of
      alternative propellant aerosol delivery systems, but at this 50-year juncture,
      what are the characteristics of these systems and what are the prospects for
      future advances? This review will consider alternative propellant aerosol
      delivery systems broadly from their inception through future opportunities and
      challenges.

PMID- 16566705
TI  - Biodegradable microspheres for parenteral delivery.
AB  - Nowadays, emphasis is being laid to development of controlled release dosage
      forms. Interest in this technology has increased steadily over the past few
      years. Although oral administration of drugs is a widely accepted route of drug
      delivery, bioavailability of drug often varies as a result of gastrointestinal
      absorption, degradation by first-pass effect, and hostile environment of
      gastrointestinal tract. Transdermal administration for percutaneous absorption of
      drug is limited by the impermeable nature of the stratum corneum. Ocular and
      nasal delivery is also unfavorable because of degradation by enzymes present in
      eye tissues and nasal mucosa. Hence, the parenteral route is the most viable
      approach in such cases. Of the various ways of achieving long-term parenteral
      drug delivery, biodegradable microspheres are one of the better means of
      controlling the release of drug over a long time. Because of the lipidic nature
      of liposomes, problems such as limited physical stability and difficulty of
      freeze-drying are encountered. Similarly, for emulsions, stability on long-term
      basis and in suspensions, rheological changes during filling, injecting, and
      storage poses limitation. Also, in all these systems, the release rate cannot be
      tailored to the needs of the patient. Parenteral controlled-release formulations
      based on biodegradable microspheres can overcome these problems and can control
      the release of drug over a predetermined time span, usually in the order of days
      to weeks to months. Various FDA-approved controlled-release parenteral
      formulations based on these biodegradable microspheres are available on the
      market, including Lupron Depot Nutropin Depot and Zoladex. This review covers
      various molecules encapsulated in biodegradable microspheres for parenteral
      delivery.

PMID- 16566707
TI  - Editorial: photodynamic therapy and detection.

PMID- 16566708
TI  - Biophysical aspects of photodynamic therapy.
AB  - Over the last three decades photodynamic therapy (PDT) has been developed to a
      useful clinical tool, a viable alternative in the treatment of cancer and other
      diseases. Several disciplines have contributed to this development: chemistry in
      the development of new photosensitizing agents, biology in the elucidation of
      cellular processes involved in PDT, pharmacology and physiology in identifying
      the mechanisms of distribution of photosensitizers in an organism, and, last but
      not least, physics in the development of better light sources, dosimetric
      concepts and construction of imaging devices, optical sensors and spectroscopic
      methods for determining sensitizer concentrations in different tissues. Physics
      and biophysics have also helped to focus on the role of pH for sensitizer
      accumulation, dose rate effects, oxygen depletion, temperature, and optical
      penetration of light of different wavelengths into various types of tissue. These
      are all important parameters for optimally effective PDT. The present review will
      give a brief, physically based, overview of PDT and then discuss some of the main
      biophysical aspects of this therapeutic modality.

PMID- 16566709
TI  - Singlet oxygen in photosensitization.
AB  - Oxygen is a ubiquitous element and a vitally important substance for life on the
      Earth, and especially for human life. Living organisms need oxygen for most, if
      not all, of their cellular functions. On the other hand, oxygen can produce
      metabolites that are toxic and potentially lethal to the same cells. Being
      reactive and chemically unstable reactive oxygen species (ROS) are the most
      important metabolites that initiate reduction and oxidation (redox) reactions
      under physiological conditions. Oxygen in its excited singlet state (1O2) is
      probably the most important intermediate in such reactions. Since the discovery
      of oxygen by Joseph Priestley in 1775 it has been recognized that oxygen can be
      both beneficial and harmful to life.

PMID- 16566710
TI  - Hydrogen peroxide, superoxide, and hydroxyl radicals are involved in the
      phototoxic action of hematoporphyrin derivative against tumor cells.
AB  - This study was aimed to estimate the participation of reactive oxygen species
      (ROS), other than singlet oxygen (1O2), in the antitumor effect of photodynamic
      therapy (PDT) with hematoporphyrin derivative (HPD) as well as to determine the
      ability of photoexcited HPD to the formation of protein peroxides that currently
      are regarded as a new form of ROS. Studies were performed on Ehrlich ascites
      carcinoma (EAC) cells, which were loaded with HPD in phosphate-buffered saline
      and then irradiated with red light at 630 run in the same buffer. Experiments
      indicated that H2O2 and oxygen radicals could mediate the tumoricidal action of
      HPD-PDT; we found that photosensitization of EAC cells with HPD leads to the
      formation of significant amounts of H2O2, superoxide (O2-.), and hydroxyl (OH.)
      radicals, which along with 1O2 were involved in photoinactivation of the cells in
      vitro. Our data showed that in EAC cells subjected to HPD-PDT, the generation
      H2O2, O2-., and OH. could be largely mediated by: (i) an increase in the activity
      of xanthine oxidase (XOD), due most probably to the conversion of xanthine
      dehydrogenase (XDH) to XOD via a Ca2+-dependent proteolytic process as well as
      oxidation of SH groups in XDH; and (ii) photooxidation of some cellular
      constituents (proteins). Another interesting finding of our studies is that in
      tumor cells subjected to HPD-PDT the Fenton-like reactions could play an
      important role in the generation of OH., and that cell-bound Cu/Zn-superoxide
      dismutase as well as catalase can protect tumor cells against the phototoxic
      action of HPD. In addition, we clearly demonstrated the ability of photoexcited
      HPD to the generation of protein peroxides in tumor cells. Studies suggest that
      1O2 is the main agent responsible for the generation of protein peroxides in EAC
      cells treated with HPD-PDT, although other ROS (H2O2, O2-., and OH.) were also
      implicated in this process. However, further work is needed to clarify the
      significance of these peroxides in the antitumor effect of PDT with HPD.

PMID- 16566711
TI  - An overview of synthetic approaches to porphyrin, phthalocyanine, and
      phenothiazine photosensitizers for photodynamic therapy.
AB  - The mechanistic basis of photodynamic therapy is reviewed briefly, and the
      factors that are important in improving photosensitizers are examined. The
      methods for preparing the three main classes of PDT photosensitizers, namely,
      porphyrins, phthalocyanines, and phenothiazines, are reviewed.

PMID- 16566712
TI  - New derivatives of 5-aminolevulinic acid for photodynamic therapy: chemical
      synthesis and porphyrin production in in vitro and in vivo biological systems.
AB  - Photodynamic therapy (PDT) has become a new treatment for several oncological and
      nononcological disorders. This procedure involves systemic or topical
      administration of a lesion-localizing photosensitizer or prodrug, followed by
      irradiation with visible light to cause singlet oxygen-induced damage to the
      target tissue. 5-aminolevulinic acid (ALA) is an endogenous precursor for several
      photosensitizing porphyrins formed by heme biosynthesis, and has been studied for
      PDT with promising results for some superficial diseases of the skin and hollow
      internal organs. Hydrophilic ALA has a limited ability to penetrate certain
      biological barriers and has a relatively low selectivity for lesions. In
      addition, its ability to induce intracellular porphyrins has been shown to be low
      compared to most esters of ALA. This stimulated a search for lipophilic
      derivatives of ALA to overcome the shortcomings of ALA. Thirty-two new esters of
      ALA were prepared and their ability to induce porphyrin formation was assessed in
      the WiDr human carcinoma cell line in vitro and in the normal skin of Balb/c nude
      mice in vivo. Branched-chain alkyl esters and substituted benzyl esters were
      found to be the most efficient porphyrin precursors of the compounds studied.

PMID- 16566713
TI  - Use of ALA and ALA derivatives for optimizing ALA-based photodynamic therapy: a
      review of our experience.
AB  - 5-Aminolevulinic acid (ALA)-based PDT has been gaining increased attention in the
      last ten years, and become an approved treatment modality for some cancers and
      other diseases. Different approaches to enhance this therapeutic modality are in
      progress, including the development of several drug delivery systems and the use
      of more lipophilic ALA derivatives. This paper focuses on our experience in this
      field.

PMID- 16566714
TI  - Regulation of porphyrin synthesis and photodynamic therapy in heavy metal
      intoxication.
AB  - Protoporphyrin IX (PpIX) synthesis by malignant cells is successfully exploited
      for photodynamic therapy (PDT) following administration of 5-aminolevulinic acid
      (ALA) and light irradiation. The influence of two environmental heavy metal
      poisons, lead and gallium, on PpIX-synthesis and ALA-PDT was studied in two neu
      ronal cell lines, SH-SY5Y neuroblastoma and PC12 pheochromocytoma. The heavy
      metal intoxication affected two of the heme-synthesis enzymes, ALA-dehydratase
      (ALAD) and porphobilinogen deaminase (PBGD). The present results show that lead
      poisoning significantly decreased the PBGD cellular level and inhibited its
      enzymatic activity, whereas the effects of gallium were less prominent. Although,
      the protein levels were reduced, the mRNA levels of PBGD remained unchanged
      during metal intoxication. These findings show additional inhibitory activity of
      lead on top of its classical effect on ALAD. Proteasome activity was enhanced
      during lead treatment, as measured by the AMC fluorigenic proteasome assay. The
      reduction in PBGD levels was not a consequence of PBGD mRNA reduced synthesis,
      which remained unchanged as shown by RT-PCR analysis. As a result of the lead
      poisoning, marked alterations in the cell cycle were observed, including a
      decreased G1 phase and an increased number of S phase cells. The efficacy of ALA
      PDT was reduced in correlation with decreased activities of the enzymes during
      lead intoxication. We may conclude that lead poisoning adversely affects the
      outcome of ALA photodynamic therapy of cancer.

PMID- 16566715
TI  - Induction of apoptosis by hexaminolevulinate-mediated photodynamic therapy in
      human colon carcinoma cell line 320DM.
AB  - Photodynamic therapy (PDT) typically involves systemic or topical administration
      of a tumor-localizing photosensitizer or prodrug and its subsequent activation by
      visible light. This results primarily in singlet oxygen-induced photodamage to
      the tumor. 5-Aminolevulinic acid (ALA) and its derivatives have recently been
      widely used for PDT due to their selective induction in tumor of endogenous
      protoporphyrin IX (PpIX), a potent photosensitizer. Although ALA-PDT has achieved
      successful results in the treatment of several clinical oncological and
      nononcological diseases, the mechanisms of this modality are still not fully
      elucidated. In the present study, the human colon carcinoma cell line 320DM was
      treated in vitro with PDT using hexaminolevulinate (HAL), a hexylester of ALA
      known to be 50 to 100 times more efficient at producing PpIX formation than ALA
      itself. PpIX production increased with increasing HAL concentrations in the cells
      and phototoxicity of the cells was enhanced with increasing light (450 nm) doses.
      HAL-PDT induced apoptotic cell death, as measured by nuclear staining of Hoechst
      33342 for fluorescence microscopy, DNA electrophoresis and TdT staining for flow
      cytometry. PDT with 5 muM of HAL and a light dose of 640 mJ/cm2 produced a 75%
      apoptotic cell population 40 hr after the treatment. Furthermore, the loss of
      mitochondrial membrane potential coincident with the release of cytochrome c from
      the mitochondria into the cytosol led to a rapid activation of caspase-9 and
      caspase-3 (an executioner), indicating that the selective damage to the
      mitochondria by HAL-PDT can induce a cytochrome-c-mediated apoptotic response in
      the 320DM cells.

PMID- 16566716
TI  - Characterization of apoptosis induced by photodynamic treatment with hypericin in
      A431 human epidermoid carcinoma cells.
AB  - Hypericin is a naturally occurring metabolite extracted from Hypericum plants and
      is regarded as a promising photosensitizing agent for applications in the frame
      of photodynamic treatment (PDT). This treatment procedure is based on the light
      induced formation of reactive oxygen species and subsequent destruction of target
      cells. We used an in vitro model system consisting of human epidermoid carcinoma
      cells (A431) and hypericin as a photosensitizer to study the time- and dose
      dependent characteristics of hypericin-PDT-based induction of cytotoxicity and
      apoptotic cell death. The induction of apoptosis by hypericin-PDT was found to
      follow a strict dose-dependent manner with a transition to necrotic cell death at
      higher doses. Apoptosis was analyzed by characteristical biochemical and
      morphological markers (activation of caspases, nuclear fragmentation and membrane
      blebbing). Time-course analysis of an almost homogenous apoptotic population of
      cells (at 1.44 J/cm2) showed a rapid increase in nuclear fragmentation and
      activation of caspases reaching a maximum at 5 hr after irradiation. Using
      specific caspase substrates, significant activation of caspase-2, -3, -6, and -9
      was found. Mitochondrial involvement during hypericin-PDT-induced apoptosis could
      be proven by a rapid reduction of the mitochondrial membrane potential;
      interestingly, the level of intracellular adenosine-5'-triphosphate (ATP) remains
      at control level for up to 6 hr post irradiation suggesting upregulation of
      glycolysis as a compensating mechanism of energy supply. Our data contribute to a
      deeper understanding of the processes involved in apoptotic cell death following
      photodynamic treatment with hypericin.

PMID- 16566717
TI  - Deposition of complement proteins on cells treated by photodynamic therapy in
      vitro.
AB  - Activation of the complement system has emerged as a critical event in the
      response of tumors to photodynamic therapy (PDT) due to its involvement in the
      vascular effects as well as in the inflammatory and immune reactions observed
      with this treatment modality. However, the exact mechanism of PDT-induced
      complement activation has not been precisely characterized. The present study
      examines the potential of PDT at the cellular level to directly activate the
      complement system. Mouse tumor SCCVII cells treated by Photofrin-based PDT and
      post-incubated in the presence of homologous (mouse) serum were analyzed by flow
      cytometry for binding of complement proteins on their surface. The results show
      that PDT induced the fixation of complement C3 protein, probably in the form of
      its activated fragments, and of the terminal membrane attacks complex of
      complement on the treated SCCVII cells. Deposition of C3/C3 fragments on human
      umbilical vein endothelial cells (HUVEC) treated by Photofrin-PDT and post
      incubated in the presence of human serum was also detected. Complement fixation
      was preferentially elevated on SCCVII cell undergoing PDT-induced apoptosis. The
      induction of surface expression of heat shock protein 70 (HSP70) on PDT-treated
      cells also triggered complement deposition, since the presence of anti-HSP70
      antibodies during the post-PDT incubation blocked the anchoring of C3/C3
      fragments to SCCVII cells. The fact that PDT-treated cells are recognized by the
      complement system as their target adds an important element for understanding the
      mechanism of tumor response to PDT.

PMID- 16566718
TI  - Photodynamic effect of curcumin on NPC/CNE2 cells.
AB  - Nasopharyngeal carcinoma (NPC) is highly prevalent in Southern China.
      Radiotherapy is the primary treatment of NPC, but the rate of tumor recurrence is
      significant. Photodynamic therapy (PDT) and the use of natural compounds become
      one of the new approaches in the investigation of NPC treatment. PDT is an
      alternate method of cancer treatment while curcumin (CUR) is a compound derived
      from the traditional Chinese medicinal (TCM) herbs. The purpose of the study
      focuses on the photodynamic effect of CUR on one of the NPC cell lines, NPC/CNE2.
      Cytotoxicity and photocytotoxicity of CUR were evaluated by 3-(4,5-dimthyl
      thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Uptake
      kinetics of CUR in NPC/CNE2 was examined by flow cytometry. The mode of cell
      death induced by CUR was studied by fluorescence microscopy. Summarizing the
      results, CUR showed dark cytotoxicity as well as photocytotoxic effects on
      NPC/CNE2 cells. LC50 of CUR in the dark was about 16 microM. The cytotoxicity of
      CUR was enhanced by the irradiation of visible light and blue filtered light
      (maximum transmittance at 300 approximately 400 nm) with light doses of 300 kJ/m2
      and 60 kJ/m2 respectively. NPC/CNE2 was found to rapidly take up CUR in the first
      hour of incubation, and the uptake kinetics steadily increased to a plateau level
      after 20 hr of incubation. Cell shrinkage and membrane bledding appeared under
      the observation of fluorescence microscopy. Such evidences proved that CUR might
      induce apoptosis on NPC/CNE2 cells. The preliminary study confirmed that CUR
      demonstrated dark cytotoxicity and photocytotoxicty to NPC/CNE2. The mode of
      action is likely to be induced by apoptotic pathway. CUR may be developed as a
      potential photosensitizer as well as a chemotherapeutic agent in clinical
      application.

PMID- 16566719
TI  - Comparison of merocyanine 540-mediated photodynamic action on leukemia cells
      between pulsed and continuous wave light sources.
AB  - Whether a pulsed laser is superior to a continuous wave (CW) light source in
      photodynamic therapy (PDT) of cancer is still unclear and contradictory in the
      literature. Although photosaturation of a sensitizer and oxygen depletion in
      tumor have been considered to be involved during pulsed laser irradiation, there
      is a lack of experimental data. In the present work several parameters such as
      the amount of merocyanine 540 (MC540) in cells, the oxygen concentration in
      cells, and the amount of photos reaching cells during pulsed laser irradiation,
      were studied to compare the MC540-mediated PDT effects of a pulsed laser and a CW
      light source on murine myeloid WEH-3B (JCS) cells in vitro. The results showed
      that the pulsed laser was less effective at cell inactivation than the CW light
      under the same irradiation dose. However, when the energy of the pulsed laser was
      reduced from 0.25 to 0.06 mJ/cm2 while keeping the total irradiation dose
      unchanged, the photoinactivation of cells was increased significantly. Based on
      the measurements and calculations for the present experimental conditions, each
      cell has about 108 MC540 molecules bound (5 microg/ml MC540 for 1 hr) and
      receives about 109 photos from 0.25 mJ/cm2 of the pulsed laser. The results
      indicate that the photosaturation of MC540 occurs in the present conditions due
      to the fact that the photons received by one cell in one laser pulse were much
      more than the numbers of MC540 molecules bound to one cell. Thus, the
      photosaturation of the photosensitizer is one of the reasons to explain the
      different efficiency in cell inactivation between the pulsed laser and CW light.

PMID- 16566720
TI  - Perylenequinones in photodynamic therapy: cellular versus vascular response.
AB  - Photodynamic therapy (PDT) is a promising new modality in the treatment of
      cancers, which employs the interaction between a tumor-localizing photosensitizer
      and light of an appropriate wavelength to bring about molecular oxygen-induced
      cell death. We have investigated the efficacy of photosensitizers from the family
      perylenequinone, namely Hypericin, Hypocrellin A and B, in the treatment of
      cancer. These photosensitizers are known as potent second generation natural
      photosensitizers that have phototherapeutic advantages over the presently used
      porphyrins. We have studied the in vitro signaling mechanism involved in the
      photodynamic action following PDT in various human carcinoma cell lines. The
      difference of tumor cell death between two modes of action i.e., vascular- and
      cellular-mediated cell death, were evaluated in order to compare treatments that
      can efficaciously eradicate tumor in xenografts model. The antivascular effect of
      PDT was demonstrated in the chick chorioallantoic membrane (CAM) model. Tumor
      therapy based on targeting the vasculature of the tumor is indeed promising as
      demonstrated in the higher relative regression percentage of treated tumor
      compared to cellular targeted PDT. The favorable tumor response derived from
      short drug-light interval mediated PDT was primarily based on the differential
      uptake of the photosensitizer into tumor-associated vasculature as opposed to the
      cellular compartments of the tumor.

PMID- 16566721
TI  - Positron emission tomography imaging of tumor response after photodynamic
      therapy.
AB  - Positron emission tomography (PET) imaging is a powerful noninvasive tool
      allowing physiological and biochemical processes to be investigated in vivo at
      the molecular level. In the clinics, it is currently being used to detect and
      stage cancer and to assess tumor response following therapy. In cancer research,
      at the preclinical level, PET in conjunction with a dedicated high-resolution
      small animal scanner can play an important role in drug development as well as in
      the evaluation of novel treatment protocols. In this paper, we review the use of
      PET in assessing tumor response to photodynamic therapy (PDT) and discuss its
      potential role in the development of novel photosensitizers. This molecular
      imaging modality is particularly promising for the real-time evaluation of tumor
      response to therapy both in terms of treatment efficacy and action mechanism.

PMID- 16566722
TI  - Avastin enhances photodynamic therapy treatment of Kaposi's sarcoma in a mouse
      tumor model.
AB  - The goal of the current study was to determine if the antiangiogenic drug Avastin
      would improve the effectiveness of Photodynamic Therapy (PDT) in a xenograft
      model of Kaposi's sarcoma (KS). Human KS-Imm tumors transplanted in nude mice
      were treated with Photofrin-mediated PDT. Expression parameters of proangiogenic
      molecules were documented and the tumoricidal effectiveness of PDT combined with
      the VEGF inhibitor Avastin was determined. PDT induced increased expression of
      HIF-1alpha, VEGF, PGE2, TNF-alpha, and IL-1beta within treated KS tumor tissue.
      Significant overexpression of KS cell derived human VEGF and to a lesser extent
      overexpression of host cell derived mouse VEGF were detected within treated
      tumors. Combining PDT with Avastin resulted in a significant increase in the long
      term responsiveness of treated KS tumors when compared to individual treatments.
      These results demonstrate for the first time that Avastin can improve PDT
      treatment effectiveness and suggest that VEGF inhibitors may ameliorate the
      clinical efficacy of PDT.

PMID- 16566723
TI  - Repetitive photodynamic therapy of malignant brain tumors.
AB  - The probability of achieving local control with current single-shot,
      intraoperative photodynamic therapy (PDT) treatments of intracerebral gliomas
      seems improbable due to the length of time required to deliver adequate light
      fluences to depths of 1-2 cm in the resection margin. Additionally, due to the
      short doubling time of many malignant gliomas, the kill rate per cell doubling
      indicates that it seems unlikely that a single treatment would be sufficient to
      prevent tumor recurrence. Multiple repetitive treatments would therefore seem
      required. In this publication we primarily review our work examining the effects
      of repetitive PDT on malignant brain tumor cells both in vitro and in vivo. The
      in vitro therapy response of human and rat glioma spheroids to 5-aminolevulinic
      acid (ALA)-mediated PDT in repetitive form was investigated. The results
      indicated that PDT repeated at relatively long intervals (weeks) was more
      effective at inhibiting spheroid growth than either daily fractionated PDT or
      single-treatment regimes. The in vivo response to repetitive treatment was
      evaluated in a rodent glioma model where BT4C cell line tumors were established
      in the brains of inbred BD-IX rats. Microfluorometry of frozen tissue sections
      showed that PpIX is produced with a 10-20:1 tumor to normal tissue selectivity
      ratio 4 hr after ALA injection. Preliminary evidence of increased efficacy of
      repetitive PDT and low fluence rate treatment is presented.

PMID- 16566724
TI  - Photoimmunotherapy for cancer treatment.
AB  - Phototherapy, with its effective dose control and light delivery, has become a
      promising modality for treating malignant and nonmalignant diseases.
      Photochemical interaction, specifically photodynamic therapy (PDT), and
      photothermal interaction have been the primary mechanisms for direct cell
      destruction in the treatment of cancers. Preclinical studies demonstrate that, in
      addition to direct local cytotoxicity, PDT can also induce systemic immune
      responses, which may enhance therapeutic effects on primary tumors and on
      metastases at distant sites. Selective photothermal therapy, using an in situ
      application of light-absorbing dye, has also proven to be an effective method for
      local treatment of tumors. When combined with immunotherapy, the effects of
      phototherapy can be amplified, potentially making the photoimmunotherapy a
      systemic treatment modality. This phototherapy-immunotherapy combination,
      particularly in conjunction with immunoadjuvant, has been used in preclinical
      studies. The efficacy and long-term effects of such a combination are summarized
      and the recent experimental results are presented. A new immunoadjuvant, glycated
      chitosan (GC), has been used to enhance photochemical and photothermal therapies.
      The PDT-GC combination in the treatment of mammary tumors and lung tumors in mice
      provided significant improvement in the long-term survival of tumor-bearing
      animals. The use of GC in dye-assisted laser photothermal therapy also provided
      long-term curative effects and antitumor immune responses in the treatment of
      metastatic tumors in rats. The immune responses induced by phototherapy and
      enhanced by immunotherapy could become important mechanism in the control of
      metastatic tumors.

PMID- 16566725
TI  - Mechanism of radiosensitization by porphyrins.
AB  - According to our previous data, hematoporphyrin dimethyl ether (HPde) at
      concentrations useful for photodynamic therapy can radiosensitize aggressive
      Ehrlich ascite carcinoma (EAT) to 2Gy irradiation inducing total tumour growth
      inhibition. The aim of this study was to further investigate the possible
      mechanism of radiosensitization of EAT by dicarboxylic porphyrin-HPde. Our
      results reveal that HPde is inducing several rearrangements in the EAT cells: 1.2
      x 10-6 M of the photosensitizer diminishes the number of cells in mitosis by a
      factor of 3, increases the number of cells in the S phase of the cell cycle,
      modifies the activities of antioxidant enzymes glutation S-transferase (GST) and
      DT-diaphorase (DTD), and eventually induces slight apoptosis. Moreover, it was
      shown that HPde is a ligand of peripheral benzodiazepine receptor (PBR). Named
      "house keeper," PBR is usually responsible for all these perturbations, which, in
      our case, act in concert with the following ionizing radiation, producing the
      interaction of two antiproliferative/destructive factors.

PMID- 16566727
TI  - Methods for detailed histopathological investigation and localization of biopsies
      from cervix uteri to improve the interpretation of autofluorescence data.
AB  - Fluorescence spectroscopy is one of many optical methods that are potentially
      clinically useful for noninvasive detection and characterization of disorders on
      the cervical part of uterus, including precancerous lesions. The cervix uteri
      exhibits a biologically complex tissue and the morphology of a biopsy is
      generally not homogenous. The standard histopathological protocol accounts only
      for the most severe condition found within the biopsy and no information is given
      on other constituents potentially influencing the recorded fluorescence spectra.
      Spectra are usually correlated, using multivariate techniques, to the
      histopathological diagnosis of the biopsies. Since the probe volume of
      fluorescence spectroscopy is considerably smaller than the extension of the
      biopsy, this can cause problems in the search for correlation between the
      fluorescence signals and the pathological structures. In addition, the
      orientation and location of the biopsies are normally not recorded. We now report
      on the first detailed histopathological protocol where numerous tissue
      parameters, such as thickness and type of the epithelium and the number of blood
      vessels, glands, and inflammatory cells, are tabulated and the orientation and
      location of the biopsy are recorded as precisely as possible. Hopefully, the use
      of this protocol together with sophisticated mathematical methods will increase
      the probability to classify cervical disorders of the uterus, including
      precancerous lesions, with high sensitivity and specificity.

PMID- 16566726
TI  - Spectroscopic measurements of photoinduced processes in human skin after topical
      application of the hexyl ester of 5-aminolevulinic acid.
AB  - Although 5-aminolevulinic acid, ALA, and its derivatives, have been widely
      studied and applied in clinical photodynamic therapy (PDT), there is still a lack
      of reliable and non-invasive methods and technologies to evaluate physiological
      parameters of relevance for the therapy, such as erythema, melanogenesis, and
      oxygen level. We have investigated the kinetics of these parameters in human skin
      in vivo during and after PDT with the hexyl ester of ALA, ALA-Hex. Furthermore,
      the depth of photosensitizer (protoporphyrin IX, PpIX) production after different
      application times was investigated. It was found that the depth increased with
      increasing application time of ALA-Hex. We also investigated the depth of PpIX
      before and after light exposure causing 50% photobleaching at 407 nm. The PpIX
      localized in superficial layers of the normal tissue was removed during the
      bleaching. Thus, after bleaching, the remaining PpIX was localized mainly in the
      deeper layers of normal tissue. We have applied fluorescence emission
      spectroscopy, fluorescence excitation spectroscopy, and reflectance spectroscopy
      in the study of the above-mentioned parameters. In conclusion, fluorescence
      excitation spectroscopy and reflectance spectroscopy are simple, useful,
      reliable, and noninvasive techniques in the evaluation of the processes taking
      place in human skin in vivo during and after PDT. Using these methods we were
      able to quantify melanogenesis, O2 level, erythema, vasoconstriction, and
      vasodilatation.

PMID- 16566728
TI  - Fluorescence diagnosis using enzyme-related metabolic abnormalities of neoplasia.
AB  - Early cancer diagnosis is of the most crucial factors determining proper patient
      management and long-term survival. Thus, there is considerable interest in
      developing more reliable methods for cancer diagnosis. Fluorescence diagnosis
      using metabolic alterations of neoplasia has emerged as a powerful new biomedical
      tool. It is characterized by superior sensitivity and selectivity over other
      methods, and it offers the possibility to obtain molecular information required
      to determine the state of the disease. Furthermore, important advancements have
      been made in generating deeper three-dimensional images in vivo by exploiting
      tissue transparency in the near-infrared region and fluorescence-mediated
      tomography, which might render fluorescence diagnosis less invasive. From basic
      principles in optics and molecular biology to the development of medical
      instrumentation and the launching of clinical trials, we have comprehensively
      compiled the basic information required to clearly understand fundamental aspects
      of fluorescence-based diagnosis.

PMID- 16566730
TI  - Facilitated delivery of ALA to inaccessible regions via bioadhesive patch
      systems.
AB  - 5-Aminolevulinic acid (ALA) is now being increasingly used in photodynamic
      therapy (PDT) and photodiagnosis (PDD) of lesions of the oral cavity, esophagus,
      and female genital tract. Clearly, topically applied creams and solutions are not
      the most suitable drug delivery systems for such moist and irregularly shaped
      areas, where shear forces may be high. As a result, such areas of the body are
      currently relatively inaccessible to efficient topical delivery of ALA. The use
      of a bioadhesive patch for topical delivery of ALA to the lower female genital
      tract and now, for the first time, to the human lip, is described. Use of the
      patch, containing 38 mg ALA cm-2, allowed successful PDT of vulval
      intraepithelial neoplasia lesions and induced protoporphyrin IX production in
      Herpes simplex lesions of the lip.

PMID- 16566729
TI  - Updated results of a phase I trial of motexafin lutetium-mediated interstitial
      photodynamic therapy in patients with locally recurrent prostate cancer.
AB  - Locally recurrent prostate cancer after treatment with radiation therapy is a
      clinical problem with few acceptable treatments. One potential treatment,
      photodynamic therapy (PDT), is a modality that uses laser light, drug
      photosensitizer, and oxygen to kill tumor cells through direct cellular
      cytotoxicity and/or through destruction of tumor vasculature. A Phase I trial of
      interstitial PDT with the photosensitizer Motexafin lutetium was initiated in men
      with locally recurrent prostate cancer. In this ongoing trial, the primary
      objective is to determine the maximally tolerated dose of Motexafin lutetium
      mediated PDT. Other objectives include evaluation of Motexafin lutetium uptake
      from prostate tissue using a spectrofluorometric assay and evaluation of optical
      properties in the human prostate. Fifteen men with biopsy-proven locally
      recurrent prostate cancer and no evidence of distant metastatic disease have been
      enrolled and 14 have been treated. Treatment plans were developed using
      transrectal ultrasound images. The PDT dose was escalated by increasing the
      Motexafin lutetium dose, increasing the 732 ran light dose, and decreasing the
      drug-light interval. Motexafin lutetium doses ranged from 0.5 to 2 mg/kg
      administered IV 24, 6, or 3 hr prior to 732 ran light delivery. The light dose,
      measured in real time with in situ spherical detectors was 25-100 J/cm2. Light
      was delivered via optical fibers inserted through a transperineal brachytherapy
      template in the operating room. Optical property measurements were made before
      and after light therapy. Prostate biopsies were obtained before and after light
      delivery for spectrofluorometric measurements of photosensitizer uptake. Fourteen
      patients have completed protocol treatment on eight dose levels without dose
      limiting toxicity. Grade I genitourinary symptoms that are PDT related have been
      observed. One patient had Grade II urinary urgency that was urinary catheter
      related. No rectal or other gastrointestinal PDT-related tox-icities have been
      observed to date. Measurements of Motexafin lutetium demonstrated the presence of
      photosensitizer in prostate tissue from all patients. Optical property
      measurements demonstrated substantial heterogeneity in the optical properties of
      the human prostate gland which supports the use of individualized treatment
      planning for prostate PDT.

PMID- 16566731
TI  - Pretreatment of plantar warts with azone enhances the effect of 5-aminolevulinic
      acid photodynamic therapy.
AB  - 5-Aminolevulinic acid (5-ALA) is a well characterized precursor in the synthesis
      of various endogenous porphyrins used in photodynamic therapy (PDT). It is most
      often administered topically into a tumor which is then irradiated with visible
      light at established wavelength to sensitize porphyrins accumulated therein. Our
      main aim in the present study was to increase the penetration of 5-ALA through
      the altered skin by application of 3% azone (1-dodecyl-azepan-2-one) before the
      application of 20% 5-ALA in patients with plantar warts: mosaic warts (MW) and
      myrmecia (MY). We also used 20% 5-ALA only to treat warts in other patients. We
      compared the therapeutic and cosmetic effects of the two treatment modalities.
      The lesions treated with modification of 5-ALA-PDT by pretreatment with azone
      responded with better effectiveness. In 18 patients subjected to 5-ALA-PDT plus
      3% azone, we observed 66.7% complete response of MW and 100% of MY following PDT
      repeated two or three times; whereas in other 18 patients treated with 5-ALA-PDT
      alone, we observed only 37.5% complete response of MW and 70% of MY. These
      results provide evidence that the pretreatment with azone should be considered as
      the step that enhances 5-ALA penetration in tissues and thus increases the
      effectiveness of applied PDT.

PMID- 16566732
TI  - Photodynamic therapy of nodular basal cell carcinoma with multifiber contact
      light delivery.
AB  - To overcome the limited treatment depth of superficial photodynamic therapy we
      investigate interstitial light delivery. In the present work the treatment light
      was delivered using a system in which three or six clear-cut fibers were placed
      in direct contact with the tumor area. This placement was thought to represent a
      step toward general purpose interstitial PDT. Twelve nodular basal cell
      carcinomas were treated employing delta-aminolevulinic acid and 635 nm laser
      irradiation. Fluorescence measurements were performed monitoring the buildup and
      subsequent bleaching of the produced sensitizer protoporphyrin IX. The treatment
      efficacy, judged at a 28-month follow-up, showed a 100% complete response. Two
      punch excisions at 7 months converted two partial responses to complete
      responses. One patient failed to appear at all follow-up sessions. The outcome of
      the treatments was comparable to superficial photodynamic therapy in terms of
      histological, clinical, and cosmetic results.

PMID- 16566733
TI  - Fluorescence diagnosis and photodynamic therapy in dermatology from experimental
      state to clinic standard methods.
AB  - The role of photodynamic therapy (PDT) in the treatment of in situ neoplasias and
      tumors of the skin is steadily increasing. An intratumoral enriched
      photosensitizer and its activation by light are the principles of photodynamic
      action. Aminolevulinic acid (ALA) has been shown to be the drug with most
      experimental and clinical use in the past. The highest efficacy with most
      selectivity in topical PDT is postulated for methyl aminolevulinate or methyl
      aminooxopenoat (MAL, MAOP, Metvix). For solar keratoses, topical PDT using MAL is
      already considered to be the treatment of choice. Epithelial skin tumors such as
      basal cell carcinomas also respond very well, however, a debulking procedure of
      the exophytic tumor tissue is an absolute prerequisite to a successful cure. In
      addition to functioning as a novel therapeutic tool, photodynamic sensitization
      of skin cancer cells is increasingly used for fluorescence diagnosis (FD) (also
      known as photodynamic diagnosis or PDD). The fluorescence of induced porphyrins
      is effective in detecting and delineating neoplastic skin areas. Future
      approaches of FD and PDT are nontumoral applications, especially psoriasis, viral
      induced diseases, or acne vulgaris. Topical PDT is well tolerated and leads to
      excellent aesthetic results with only minor side effects.

PMID- 16566734
TI  - Photodynamic applications in superficial bladder cancer: facts and hopes!
AB  - As a disease characterized by a polymorphic and fluctuant nature in its
      evolution, superficial transitional cell carcinoma of the bladder remains a
      perpetual therapeutic challenge. This raises a great interest in the development
      of new diagnostic and therapeutic photodynamic applications. This article
      describes recent facts in the field of bladder cancer photodiagnosis and gives a
      survey on ongoing research in photodynamic therapy. Fluorescence cystoscopy
      induced by different aminolevulinic acid compounds (e.g., ALA-HAL) is well
      accepted in the urological community as a user-friendly new diagnostic tool in
      the endoscopic management of bladder tumors and CIS. Photodynamic therapy based
      on the same photosensitizing agents remains experimental, but recent results
      raise hopes of new therapeutic directions.

PMID- 16566735
TI  - Photodynamic therapy and detection of high-grade gliomas.
AB  - The first reported use of photodynamic therapy (PDT) for the treatment of high
      grade gliomas occurred in 1981. In the intervening years there have been
      relatively few clinical trials to investigate the efficacy of this therapeutic
      modality for the treatment of gliomas. This is due, in part, to the rarity of the
      disease, and the ever growing list of novel therapies that PDT must compete
      against. These factors make accrual of patients for clinical trials a difficult
      proposition. During the mid-1990s, a number of reviews were published that
      effectively summarized the status of PDT for the management of high-grade
      gliomas. The intent of the present work is to provide an update of recent
      developments (1996-2004) in PDT and photodynamic detection (PDD) of gliomas, in
      particular, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA).

PMID- 16566736
TI  - PDT in clinics: indications, results, and markets.
AB  - Photodynamic therapy (PDT) is based on the selective light activation of an
      exogenously given drug to patients. PDT acts mainly on cell membranes either of
      neovascular endothelial cells or of cancer cells leading to cancer cell death.
      Six drugs are now marketed based on clinical assays in various indications, which
      showed a clear cost efficiency as compared to other classical procedures. PDT is
      easy to handle and can be performed in medical installations fitting the
      conditions of health care in developing countries. Its cost effectiveness could
      represent an appropriate solution to the increasing number of cancers of various
      origin. However despite all the clinical results now available, PDT development
      remains slow. The reasons for this situation include cost of development,
      intellectual property, and competition between pharmaceutical companies.

PMID- 16566737
TI  - Photodynamic therapy as an alternative antimicrobial modality for oral
      infections.
AB  - Infections of the mouth are mostly local in nature, but if left untreated, may
      lead to potentially life-threatening conditions. Mouth infections, such as
      caries, pulpitis, periodontal disease, and oral mucosal infections, such as mouth
      ulcers, are readily accessible and thus well suited to photodynamic therapy
      (PDT). Many organisms, which may cause infections in the oral cavity, have been
      found to be susceptible to PDT to varying degrees. Several photosensitizers have
      been shown to be effective against target organisms without inducing damage to
      the host tissues. The use of appropriate photosensitizers and light doses can
      eradicate virtually all organisms in the region, but in the oral cavity where
      there is a balance of native microflora, this would potentially be a problem
      leading to the overgrowth of opportunistic organisms. This may be overcome using
      a photosensitizer linked to an antibody recognizing the target organisms. At
      present, treatment of infections with PDT appears best for localized and
      superficial infections. Treatment of deeply seated infections, such as abscesses,
      may also be possible with improvements in the delivery of the sensitizer and
      light. PDT has the potential to become established as an alternative
      antimicrobial approach for oral infections and deserves further evaluation.

PMID- 16566738
TI  - Photodynamic therapy of microbial infections: state of the art and perspectives.
AB  - Photodynamic therapy (PDT) is coming of age as an efficient alternative treatment
      for microbial infections, a problem which is presently aggravated by the
      increasingly widespread diffusion of antibiotic-resistant microbial strains. In
      particular, the use of red light-absorbing photosensitizers as photodynamic
      antimicrobial agents is characterized by various favorable features, including:
      (a) the broad spectrum of antimicrobial action of selected phenothiazines,
      porphyrins, and phthalocyanines, which promote the photosensitized inactivation
      of Gram(+) and Gram(-) bacteria, fungi, mycoplasma, and parasites by using one
      phototherapeutic protocol and mild irradiation conditions; (b)
      porphyrins/phthalocyanines display no appreciable toxicity in the dark at
      photochemically active doses; (c) microbial cell death is primarily a consequence
      of membrane photodamage through a typically multitarget process, which minimizes
      the risk of both the onset of mutagenic processes and the selection of
      photoresistant cells; (d) such photosensitizers act with essentially identical
      efficiency against both wild and antibiotic-resistant strains, whereas no
      selection of photoresistant microbial pathogens has been observed; (e) a
      combination between antibiotic-based and photodynamic therapy is possible. A
      typical example of phthalocyanine-sensitized photoinactivation of methicillin
      resistant Staphylococcus aureus (MRSA) is provided. At present, antimicrobial PDT
      appears to be especially convenient for the treatment of localized infections,
      such as oral candidosis, periodontitis or chronic wounds.

PMID- 16566740
TI  - Outstanding scientist of the year 2006: Rogel Patawaran, BS.
AB  - Rogel Patawaran is cofounder of iQSecure Solutions, Inc., a secure web mail
      company, which began in 2002 and is currently based in Santa Monica, California.
      Its unique service enables hospitals, clinics, and doctors' offices the
      opportunity to have secure web-based video and telephone conferencing by simply
      switching online services offered by this innovative company. In addition, he is
      cofounder of AuthoTecq, based in Long Beach, California, and inventor of the
      AuthoTecq system in 1999. The AuthoTecq system is an online credit card
      processing company. Rogel Patawaran sought to remedy one of the problems facing
      users of internet transactions. Because internet merchants act as their own
      gateway for financial transactions, they have been storing credit card numbers in
      their own databases, thereby failing to address the necessary security provisions
      involved in the storage of such sensitive information. AuthoTecq removes this
      responsibility from the merchant by processing financial transactions on behalf
      of the merchants. Its system dramatically reduces credit card theft, and thereby
      decreases the amount of credit card fraud. In his landmark book Saving Lives &
      Saving Money, Newt Gingrich, former Speaker of House of Representatives,
      describes a new approach to the challenge of creating a better system of personal
      health and health care for the 21st century, a system that saves lives and saves
      money. He indicates that you could be visiting a clinic with electronic medical
      records, electronic laboratory reports, and electronic drug prescriptions. This
      entirely electronic clinic saves money and lives because it is far more accurate
      than a paper system. Such clinics exist at the Kaiser Permanente Hospitals, the
      Mayo Clinic in Jacksonville, Florida, the Cleveland Clinic, many Harvard
      hospitals, and all Veteran Administration hospitals in the US. He indicates that
      healthcare is the only industry in America that can give you a disease and then
      charge you to cure it. He further reports that out of 100 hospital patients, five
      or six will be the victim of a preventable error. He states that medication
      errors alone kill 7000 people each year, adding $2 billion to the overall cost of
      healthcare. He stresses that these 7000 needless deaths are not only unacceptable
      but un-American as well. During the 1990s, the pharmaceutical industry sought
      help from the Food and Drug Administration (FDA) to develop a standard by which a
      paperless system could be adopted for healthcare. In March of 1997, the FDA
      issued its final ruling, which established the criteria for which the FDA will
      recognize the transmission of authenticity within electronic data as well as
      establishing standards of authenticity for electronic data equivalent to the
      validity of signatures on paper documents and records. The FDA also recognizes
      the growth that can be experienced by converting healthcare technology to a
      paperless system, such as the expediting of patient files in a more organized
      manner, increasing the speed of file transfer of such documents, reducing
      prescription errors, enabling computer-generated data analysis and statistics,
      and reducing storage space. Rogel Patawaran and his colleagues also realized that
      electronic healthcare technology using the highest standard of data encryption to
      transfer data could also dramatically improve the safety of patients in our
      nation and the world. To answer the needs within healthcare technology, Rogel
      Patawaran created a system for healthcare providers using the most superior
      encryption methods, and in the process creating iQSolutions, Inc. Its web mail
      system uses the Public Key Infrastructure (PKI) format, which is the strongest
      known encryption format. PKI is used in combination with the Advance Encryption
      Standard (AES) digital encryption algorithm, which is the current algorithm used
      by banks and government agencies, thereby protecting the privacy and accuracy of
      the information. Rogel Patawaran's remarkable contributions to the encryption
      process will aid in the number of lives saved as well as helping to avoid medical
      malpractice by ensuring the accuracy of medical records, as well as reducing the
      number of medication errors or inappropriate prescriptions being filled. These
      remarkable accomplishments in patient safety are accomplished at a rapid speed
      that ensures that data-sensitive patient files can be securely transmitted
      between and within hospitals. Finally, with the growing need for an electronic
      system within the medical field, doctors will be able to securely access all such
      data from anywhere and at any time, thus reducing the age-old problem of time
      constraints that a paper system presented doctors and hospitals alike. In
      recognition of Rogel Patawaran's contributions to the medical field through the
      use of encryption teamed with the transferring of sensitive data such as hospital
      records, Rogel Patawaran has been selected as the Outstanding Scientist of 2006.

PMID- 16566739
TI  - Photochemical internalization (PCI): a new modality for light activation of
      endocytosed therapeuticals.
AB  - Photochemical internalization (PCI) is a new technology, where certain
      photosensitizing substances (photosensitizers) are used to improve the
      utilization of macromolecules for cancer therapy, in a site-specific manner.
      Degradation of macromolecules in endocytic vesicles after uptake by endocytosis
      is a major intracellular barrier for the therapeutic application of molecules
      having intracellular targets of action. PCI is based on the light activation of
      photosensitizers specifically located in the membrane of endocytic vesicles
      inducing the rupture of this membrane upon illumination. Thereby endocytosed
      molecules can be released to reach their target of action before being degraded
      in lysosomes. This has been shown to enhance the biological activity of a large
      variety of macromolecules and other molecules that do not readily penetrate the
      plasma membrane, including type I ribosome-inactivating proteins (RIPs),
      immunotoxins, gene-encoding plasmids, adenovirus, peptidenucleic acids, and the
      chemotherapeuticum bleomycin. In several cases up to a 100-fold increase in
      biological activity has been observed. This article reviews the background and
      present status of PCI.

PMID- 16566741
TI  - Revolutionary advances in medical waste management. The Sanitec system.
AB  - It is the purpose of this collective review to provide a detailed outline of a
      revolutionary medical waste disposal system that should be used in all medical
      centers in the world to prevent pollution of our planet from medical waste. The
      Sanitec medical waste disposal system consists of the following seven components:
      (1) an all-weather steel enclosure of the waste management system, allowing it to
      be used inside or outside of the hospital center; (2) an automatic mechanical
      lift-and-load system that protects the workers from devastating back injuries;
      (3) a sophisticated shredding system designed for medical waste; (4) a series of
      air filters including the High Efficiency Particulate Air (HEPA) filter; (5)
      microwave disinfection of the medical waste material; (6) a waste compactor or
      dumpster; and (7) an onboard microprocessor. It must be emphasized that this
      waste management system can be used either inside or outside the hospital. From
      start to finish, the Sanitec Microwave Disinfection system is designed to provide
      process and engineering controls that assure complete disinfection and
      destruction, while minimizing the operator's exposure to risk. There are numerous
      technologic benefits to the Sanitec systems, including environmental,
      operational, physical, and disinfection efficiency as well as waste residue
      disinfection. Wastes treated through the Sanitec system are thoroughly
      disinfected, unrecognizable, and reduced in volume by approximately 80% (saving
      valuable landfill space and reducing hauling requirements and costs). They are
      acceptable in any municipal solid waste program. Sanitec's Zero Pollution
      Advantage is augmented by a complete range of services, including installation,
      startup, testing, training, maintenance, and repair, over the life of this
      system. The Sanitec waste management system has essentially been designed to
      provide the best overall solution to the customer, when that customer actually
      looks at the total cost of dealing with the medical waste issue. The Sanitec
      system is the right choice for healthcare and medical waste professionals around
      the world.

PMID- 16566742
TI  - A revolutionary advance in skin closure compared to current methods.
AB  - Six pigs were used to evaluate the influence of three separate modalities on
      contaminated wounds. Full-thickness skin wounds on the abdomen were contaminated
      with 10(4) or 10(5) Staphylococcus aureus and then closed with one of three
      methods. The three closure modalities included (1) a new absorbable staple
      (Insorb) placed in the subcuticular tissue, (2) a braided Vicryl suture, and (3)
      percutaneous metal staples. Any foreign body material implanted in tissue
      increases the risk of infection at that site. Wound closure always involves the
      use of a foreign body. Historically, sutures have been the primary material used
      to close tissue. The newer synthetic sutures are significangly more biodegradable
      and cause less infection than sutures composed of protein, such as silk and
      catgut. Metal staples are also associated with a low risk of infection. Recently,
      Incisive Surgical, Inc. (Plymouth, Minnesota) has developed an absorbable polymer
      staple specifically for subcuticular skin closure. The purpose of this study was
      to compare the new Insorb staple to both an absorbable polymer suture and a metal
      staple. Wound infection was assessed 7 days after closure by clinical signs and
      quantitative bacterial swabs. The results demonstrated that wounds closed with
      Insorb staples had the lowest incidence (33%) of infection, followed by
      percutaneous metal staples (44%). All wounds (100%) closed with Vicryl suture
      became infected. The incidence of wound infection directly correlated with the
      level of quantitative bacterial count at analysis. The Insorb staple was
      associated with significantly reduced closure time, less inflammation and
      infection, and better aesthetic result compared to Vicryl. Compared to metal
      staples, the Insorb subcuticular staplers demonstrated comparable closure time
      without the need for later staple removal. In conclusion, the closure of
      contaminated wounds with the Insorb staples is a superior choice to Vicryl suture
      because they have a significantly (p = 0.009) lower incidence of infection. The
      Insorb staple is a revolutionary advance in subcuticular skin stapling.

PMID- 16566743
TI  - Scientific basis for the selection of absorbent underpads that remain securely
      attached to underlying bed or chair.
AB  - The occurrence of pressure ulcers in patients is very high in certain high-risk
      groups. These special high-risk groups include elderly patients, patients with
      spinal cord injuries, or any individual with an impaired ability to reposition.
      Prevention of pressure ulcers is by far the best treatment of this condition,
      warranting certain interventions and preventive measures. One major risk factor
      to be minimized is the exposure of skin to moisture. Underpads are often used to
      protect the skin of patients who are incontinent. These products effectively
      absorb moisture and present a quick-drying surface to the skin. The construction
      of an underpad should accomplish three goals. First, its backing should have a
      low coefficient of friction to prevent frictional skin injuries. Second, an inner
      absorbent core should rapidly contain moisture and disseminate it throughout the
      entire pad. Third, the core and coverstock should successfully work together to
      retain moisture and prevent wet-back or fluid return. The purpose of this study
      was to determine the performance of three commercially available underpads in
      reducing the development of pressure sores in patients at high risk. In this
      study we selected three underpads that could be securely attached to either the
      underlying bed or the chair. The three performance parameters examined were
      absorbent capacity, wetback prevention, and holding security of the underpads.
      Measurements of these performance parameters can be easily replicated in other
      laboratories. The results of these studies provide a scientific basis for
      selecting and purchasing an underpad to prevent pressure ulcers in patients. In
      this comprehensive evaluation, we assess an absorbent underpad with polyethylene
      flaps and two absorbent underpads with adhesive. The absorbent capacity results
      showed Tranquility SlimLine Peach Sheet to be the most absorbent. The wet-back
      results showed Tranquility SlimLine Peach Sheet to be the only underpad with no
      wet-back, with no fluid returning through the coverstock. The Tranquility
      SlimLine Peach Sheet Underpad has four adhesive strips attached to each of the
      four ends of the underpad surface. These 5 cm long strips secure well to the seat
      of a wheelchair or chair. In contrast, they do not maintain secure attachment to
      a bed sheet, making the bed sheet vulnerable to urine or stool penetration. When
      the clinical staff used the Tuckable on the bed surface, they were all impressed
      by the secure fit of the plastic wings, which easily tucked around the mattress.
      The wings remained in place throughout the night. Realizing the stability of the
      Tuckable underpads, the clinical staff suggested that the Tuckable underpad be
      placed first on the bed, then the Tranquility SlimLine Peach Sheet can be placed
      on top of the Tuckable underpad, using the four adhesive strips to attach it to
      the surface of the Tuckable underpad. All of the staff were impressed that the
      adhesive strips remained securely attached to the Tuckable. This clinical
      decision was found to be very cost efficient, because the Tuckable could remain
      in place more than a week without changing. Even though we have developed a
      unique scientific basis for the selection of underpads for use on either chairs
      or beds, it can be a financial challenge to the patient or healthcare setting to
      use these products, because Medicare provides no reimbursement for underpads, an
      invitation to pressure ulcer formation. In the absence of responsible federal
      government policy, we are making recommendations for the selection of a cost
      conscious and responsible company that sells incontinence products--Home Deliver
      Incontinent Supplies Co., Inc., (HDIS), Olivette, Missouri.

PMID- 16566744
TI  - Anterior cruciate reconstruction with bioactive Leeds-Keio ligament (LKII):
      preliminary report.
AB  - The scaffold type Leeds-Keio artificial ligament (LK) for ligament reconstruction
      of the knee provides sufficient strength to require minimal sacrifice of
      autogenous tissue. This implant works not only as prosthesis but also as scaffold
      onto which natural tissue grows from the synovium. LK has been in clinical use
      for anterior cruciate ligament (ACL) reconstruction since 1982, although the
      operative procedure has been modified and has undergone significant development
      since that time. Recently, we developed radio frequency-generated glow discharge
      (RFGGD)-treated LK ligament (LKII, previously indicated as Bio-LK) to improve
      tissue induction and reported that cell proliferation and cell attachment to
      artificial fibers increased considerably with this hydrophilic treatment. In this
      study, we report the findings of reconstructed ACL using LKII, which has been in
      clinical use since 2003. At reconstruction, LKII was covered with the remnant of
      the original ACL as much as possible in order to preserve the nerve ending
      system. Thirteen cases with over 12 months' postoperative history were reviewed.
      Knee stability was regained after reconstruction without any complications such
      as joint effusion and chronic synovitis. In one case, postoperative arthroscopy
      showed that the reconstructed ACL was completely covered with newly formed tissue
      at 8 weeks postoperatively. Biopsy revealed abundant fibroblasts, collagenous
      fibers, and vessels around the artificial fibers without marked inflammatory
      findings. Transmission electron microscope study showed abundant thin collagen
      fibers, which demonstrated regular orientation to some extent. Fibroblasts were
      observed with extensive amount of rough endoplasmic reticulum. According to these
      results, we consider LKII to be superior to LK in tissue induction and
      maturation.

PMID- 16566745
TI  - Setting properties of four acrylic and two calcium-phosphate cements used in
      vertebroplasty.
AB  - STUDY DESIGN: Experimental study conducted in the laboratory with six different
      bone cements. OBJECTIVES: To isolate the thermal properties of conventional and
      emerging bone cements used in vertebroplasty and to characterize their setting
      behavior. SUMMARY OF BACKGROUND DATA: The heat released during setting has been
      linked to the desirable effects of pain relief and tumor destruction and to the
      undesirable effect of thermal necrosis of surrounding tissue. However, there are
      currently no studies that disconnect the exothermic reaction of the cements from
      the media in which they occur. Before the combined thermal effect is examined, it
      is important to understand the setting properties of cements alone. METHODS:
      Thirty independent experiments were conducted with four PMMA cements
      (Cranioplastic, Vertebroplastic, Palacos LV-40, Antibiotic Simplex) and two
      calcium-phosphate cements (chronOS Inject and Biopex) in accordance with ASTM
      standard F 451-99a. A thermocouple was placed in the center of the cement mass,
      and the temperature-versus-time measurements were recorded. RESULTS: The calcium
      phosphate cements took over half an hour to reach their maximum temperature,
      which was only 3-4 degrees C higher than the ambient temperature. The temperature
      increase for the acrylic cements was between 16 and 23 degrees C, and it took
      about 15 minutes to reach the maximum temperature. The variation within the
      groups was also important. CONCLUSION: The exothermic reaction of calcium
      phosphate cements appears to be insignificant. Although the acrylic cements
      release considerably greater heat in a much shorter time period, it does not
      appear that their temperature is sufficiently high to cause extensive thermal
      injury. However, variations within each group must be considered along with the
      intended use when deciding on the cement to be used.

PMID- 16566746
TI  - Collective review: bioactive implants coated with poly(D,L-lactide) and growth
      factors IGF-I, TGF-beta1, or BMP-2 for stimulation of fracture healing.
AB  - Demographic data reveal that due to the increasing aging of the population,
      complications with the musculoskeletal system will increase in the next years.
      One major problem in orthopedic and trauma surgery are the delayed healing or non
      unions of long bone fractures. The exogenous application of growth factors can
      stimulate the bone healing to reduce these complications. Beside the choice of
      the optimal growth factor the application system is important. Therefore, we
      developed a new bioactive coating method for implants, which is based on a
      biodegradable poly(D,L-lactide) (coating thickness: 10 mum). This coating allows
      the incorporation of growth factors and the controlled release of these factors
      during the healing process without the need for further devices. The effect of
      different growth factors (IGF-I, TGF-beta1, and BMP-2) locally released from
      coated intramedullary implants on fracture healing was investigated with
      biomechanical and histological analysis in rats. All investigated growth factors
      stimulated the fracture healing as assessed with biomechanical tests and
      histological analysis. The local application of combined IGF-I and TGF-beta1 had
      the most stimulating effect on fracture healing, followed by the effect of BMP-2,
      IGF-I, and TGF-beta1 alone. Bioactive coating of biomechanical well-established
      implants can on the one hand stabilize the fracture and on the other hand
      stimulate healing processes to increase healing and to reduce the rate of
      complications.

PMID- 16566747
TI  - Scanning electron microscope fractography of induced fatigue-damaged saline
      breast implants.
AB  - Breast implant strength and durability is presently an important topic in
      biomaterials science. Research studies are being conducted to determine the
      mechanisms and rates of failure in order to assess the in vivo performance of
      breast implants. Fatigue life is a measure of breast implant durability since
      fatigue failure is a potential in vivo failure mechanism. This study describes
      the characterization of the fracture surface morphology of breast implant shell
      regions that have failed due to cyclic fatigue. Saline breast implants were
      fatigue tested to failure using a laboratory apparatus in which flat plates
      cyclically compressed the implants. The implants were unimplanted control devices
      of both textured and smooth saline implants. The failure surfaces of the fatigued
      shells were examined using scanning electron microscopy (SEM). The morphological
      features of the failure surfaces are described for implants with short and long
      fatigue lifetimes. The details of both the inside and outside surfaces of the
      shell at the failure location are described. Two different modes of failure were
      observed in both the textured and smooth shells. These modes depend on the
      magnitude of the cyclic load and corresponding number of fatigue cycles at
      failure. The first mode is a tear in the shell of about 18 mm in length, and the
      second mode is a pinhole approximately 1 mm in diameter. Details of the surface
      morphology for these two types of failure modes and shell thickness data are
      presented herein. There was no significant change in the crosslink density of the
      shell as a result of fatigue.

PMID- 16566748
TI  - Implant-associated infections: an overview.
AB  - The discovery of a 5500-year-old dental implant near Gebel Ramlah, Egypt, marks
      the earliest discovery of a medical prosthesis. It would not be until the 20th
      century, however, that this ancient concept would resurface on a wide scale
      basis. With the introduction of physiologically inert biomaterials in the 1950s,
      the field of surgical implants has emerged as arguably one of the greatest
      medical advancements of our time. It is now estimated that millions of patients
      worldwide have received some type of prosthesis. This forces us to appreciate the
      impact of implant-associated infections on patients today and mandates that we as
      a medical community be prepared to manage these infections effectively. This
      article provides an in-depth review of the current most commonly used prosthetic
      devices and the infections that accompany them. We examine the epidemiology,
      diagnosis, prevention, and treatment of various implant-associated infections
      within the fields of general, plastic, orthopedic, dental, and neurosurgery. We
      will highlight the recent technological advancements and future prospects. We
      will also draw attention to the need for further research in this ever growing
      field.

PMID- 16566749
TI  - Syneture stainless STEEL suture. A collective review of its performance in
      surgical wound closure.
AB  - Syneture (division of U.S. Surgical, division of Tyco Healthcare, Norwalk,
      Connecticut, USA) STEEL sutures are monofilament stainless steel sutures composed
      of 316L stainless steel conforming to ASTM Standard F138 grade 2 (" Stainless
      steel bar and wire for surgical implant"). STEEL sutures meet all requirements
      established by the United States Pharmacopeia (USP) for nonabsorbable surgical
      sutures. Steel sutures are for use in abdominal wound closure, intestinal
      anastomosis, hernia repair, sternal closure, and skin closure. They are attached
      to the following types of surgical needles: Roto-Grip Needles and SCC Needle. The
      sutures and needles are packaged in a Mylar/Tyvek outer envelope. The purposes of
      this clinical review are two fold. First, we will report the performance of the
      Syneture STEEL suture product in the largest studies of suture performance ever
      reported in the literature. In addition, we will provide comprehensive
      information from the surgical literature that highlights the unique benefits of
      stainless steel sutures for the following wound closure techniques: sternal
      fixation, abdominal wound repair, inguinal hernia repair, and skin wound closure.
      Consorta Inc. (Rolling Meadows, Illinois), a leading healthcare resource
      management group purchasing organization, and Syneture, jointly with a clinician
      task force, designed a reproducible surgical evaluation program for needles and
      sutures in a large cooperative of healthcare systems. Because of the subjective
      nature of the more commonly used suture selection techniques, a nonexperimental
      observational study approach was designed to replace perception of performance
      characteristics with actual clinical experience. In a report involving 19
      Consorta shareholder hospitals, they discussed the preliminary part (Phase I) of
      a large nonexperimental observational study of the clinical performance of
      surgical needles and sutures. Performance characteristics of the sutures and
      needles produced by Syneture that were evaluated in 3407 surgical procedures
      included packaging/ease of opening, needle strength and sharpness, tissue drag,
      knot security, tensile strength, clinically acceptable determinations, and
      clinically unacceptable determinations. In this preliminary study, the surgeons
      concluded that the needles and sutures were clinically acceptable in 98.1% of the
      evaluations. Armed with this favorable experience, we wanted to expand this
      observational study to an entirely new group of shareholder hospitals that had a
      larger number of participating hospitals (Phase I, 19 hospitals; Phase II, 42
      hospitals). This more than doubling of hospital observational base dramatically
      increased the number of patients and performance evaluations. In the Phase II
      expanded program involving 42 hospitals, the number of patients (8939) and the
      number of evaluations (25,545) were more than twofold the preliminary study. In
      the phase I multicentric evaluation of Syneture surgical sutures, the performance
      of 9266 sutures was evaluated. Of these performance evaluations, 130 evaluations
      focused on Syneture STEEL sutures. The surgeons were especially pleased by the
      performance of this suture product, with 129 Syneture STEEL products being judged
      as clinically acceptable in their performance. Only one Syneture STEEL suture was
      judged to be unacceptable in its performance, resulting in a 99.2% acceptability
      rating. In the expanded phase II evaluation of Syneture suture products, the
      performance evaluation involved 25,545 surgical suture evaluations. The
      performance of Syneture STEEL sutures was judged in 215 cases. Of these product
      performance evaluations, 207 were judged to be clinically acceptable in their
      performance (96.3%). It is important to emphasize that the phase I and phase II
      observational studies evaluated the performance of other sutures besides
      monofilament steel sutures. These comprehensive suture and needle performance
      evaluations included the following additional sutures: Plain Gut, Mild Chromic
      Gut, Chromic Gut, DEXON II, DEXON S, MAXON, BIOSYN, SOFSILK, SURGILON, BRALON,
      MONOSOF, DERMALON, SURGIDAC, POLY-SORB, TI.CRON, SURGIPRO, SURGIPRO II, NOVAFIL,
      VASCUFIL, and FLEXON. Finally, we provide a collective review of the literature
      that shows the reliable performance of monofilament stainless steel sutures in
      the following wound closure techniques: sternal fixation, abdominal wound
      closure, inguinal hernia repair, and skin wound closure.

PMID- 16566750
TI  - Evidence for a dynamic role for homocitrate during nitrogen fixation: the effect
      of substitution at the alpha-Lys426 position in MoFe-protein of Azotobacter
      vinelandii.
AB  - Although it is generally accepted that the active site of nitrogenase is located
      on the FeMo-cofactor, the exact site(s) of N2 binding and reduction remain the
      subject of continuing debate, with both molybdenum and iron atoms being suggested
      as key players. The current consensus favours binding of acetylene and some other
      non-biologically relevant substrates to the central iron atoms of the FeMo
      cofactor [Dos Santos, Igarashi, Lee, Hoffman, Seefeldt and Dean (2005) Acc. Chem.
      Res. 38, 208-214]. The reduction of N2 is, however, a more demanding process than
      reduction of these alternative substrates because it has a much higher activation
      energy and does not bind until three electrons have been accumulated on the
      enzyme. The possible conversion of bidentate into monodentate homocitrate on this
      three electron-reduced species has been proposed to free up a binding site for N2
      on the molybdenum atom. One of the features of this hypothesis is that alpha
      Lys426 facilitates chelate ring opening and subsequent orientation of the
      monodentate homocitrate by forming a specific hydrogen bond to the homocitrate 
      CH2CH2CO2- carboxylate group. In support of this concept, we show that mutation
      of alpha-Lys426 can selectively perturb N2 reduction without affecting acetylene
      reduction. We interpret our experimental observations in the light of a detailed
      molecular mechanics modelling study of the wild-type and altered MoFe
      nitrogenases.

PMID- 16566751
TI  - Identification and characterization of Thermoplasma acidophilum glyceraldehyde
      dehydrogenase: a new class of NADP+-specific aldehyde dehydrogenase.
AB  - Thermoacidophilic archaea such as Thermoplasma acidophilum and Sulfolobus
      solfataricus are known to metabolize D-glucose via the nED (non-phosphorylated
      Entner-Doudoroff) pathway. In the present study, we identified and characterized
      a glyceraldehyde dehydrogenase involved in the downstream portion of the nED
      pathway. This glyceraldehyde dehydrogenase was purified from T. acidophilum cell
      extracts by sequential chromatography on DEAE-Sepharose, Q-Sepharose, Phenyl
      Sepharose and Affi-Gel Blue columns. SDS/PAGE of the purified enzyme showed a
      molecular mass of approx. 53 kDa, whereas the molecular mass of the native
      protein was 215 kDa, indicating that glyceraldehyde dehydrogenase is a tetrameric
      protein. By MALDI-TOF-MS (matrix-assisted laser-desorption ionization-time-of
      flight MS) peptide fingerprinting of the purified protein, it was found that the
      gene product of Ta0809 in the T. acidophilum genome database corresponds to the
      purified glyceraldehyde dehydrogenase. The native enzyme showed the highest
      activity towards glyceraldehyde, but no activity towards aliphatic or aromatic
      aldehydes, and no activity when NAD+ was substituted for NADP+. Analysis of the
      amino acid sequence and enzyme inhibition studies indicated that this
      glyceraldehyde dehydrogenase belongs to the ALDH (aldehyde dehydrogenase)
      superfamily. BLAST searches showed that homologues of the Ta0809 protein are not
      present in the Sulfolobus genome. Possible differences between T. acidophilum
      (Euryarchaeota) and S. solfataricus (Crenarchaeaota) in terms of the glycolytic
      pathway are thus expected.

PMID- 16566752
TI  - Tumour necrosis factor alpha causes hypoferraemia and reduced intestinal iron
      absorption in mice.
AB  - Cytokines are implicated in the anaemia of chronic disease by reducing
      erythropoiesis and increasing iron sequestration in the reticuloendotheial
      system. However, the effect of cytokines, in particular TNFalpha (tumour necrosis
      factor alpha), on small bowel iron uptake and iron-transporter expression remains
      unclear. In the present study, we subjected CD1 male mice to intraperitoneal
      injection with TNFalpha (10 ng/mouse) and then examined the expression and
      localization of DMT1 (divalent metal transporter 1), IREG1 (iron-regulated
      protein 1) and ferritin in duodenum. Liver and spleen samples were used to
      determine hepcidin mRNA expression. Changes in serum iron and iron loading of
      duodenum, spleen and liver were also determined. We found a significant (P<0.05)
      fall in serum iron 3 h post-TNFalpha exposure. This was coincident with increased
      iron deposition in the spleen. After 24 h of exposure, there was a significant
      decrease in duodenal iron transfer (P<0.05) coincident with increased enterocyte
      ferritin expression (P<0.05) and re-localization of IREG1 from the basolateral
      enterocyte membrane. Hepatic hepcidin mRNA levels remained unchanged, whereas
      splenic hepcidin mRNA expression was reduced at 24 h. In conclusion, we provide
      evidence that TNFalpha may contribute to anaemia of chronic disease by iron
      sequestration in the spleen and by reduced duodenal iron transfer, which seems to
      be due to increased enterocyte iron binding by ferritin and a loss of IREG1
      function. These observations were independent of hepcidin mRNA levels.

PMID- 16566753
TI  - Using the acetabulum to estimate age at death of adult males.
AB  - The acetabular region is often present and adequately preserved in adult human
      skeletal remains. Close morphological examination of the 242 left male os coxae
      from the identified collection of Coimbra (Portugal) has enabled the recognition
      of seven variables that can be used to estimate age at death. This paper
      describes these variables and argues their appropriateness by analyzing the
      correlation between these criteria and the age, the intra- and interobserver
      consistence, and the accuracy in age prediction using Bayesian inference to
      estimate age of identified specimens. Results show significant close correlation
      between the acetabular criteria and age, nonsignificant differences in intra- and
      interobserver test, and 89% accuracy in Bayes prediction. Obtained estimated age
      of the specimens had similar accuracy in all ages. These results indicate that
      these seven variables, based on the acetabular area, are potentially useful to
      estimate age at death for adult specimens.

PMID- 16566754
TI  - Histological age prediction from the femur in a contemporary Dutch sample. The
      decrease of nonremodeled bone in the anterior cortex.
AB  - This paper presents an uncomplicated and minimally invasive method for age-at
      death determination in a contemporary Dutch (West European) population, by
      modifying the approach of assessment based on the age-related remodeling of bone
      tissue. In contrast to the usual "osteon count," a "non-remodeled tissue count"
      is undertaken. To optimize the method, proper zeroing of the polarization filter
      set of the microscope is essential. Instructions for setting the filters are
      given. A sample of femoral shaft segments totaling 162 individuals with ages
      ranging from 15 to 96 years is analyzed. Subperiosteal quantitative assessments
      are recorded at the most anterior point of the femoral shaft and also at points
      25 degrees to the left and to the right of that point. Interobserver agreement in
      the assessments shows an acceptable degree of correlation. Bone remodeling with
      age does not progress in a linear, but in a curvilinear manner. Dependence of
      predicted age on nonremodeled surface counts in the analyzed areas of the
      anterior cortex of the femur appears to be significant. A set of regression
      equations is given. Sex can be ignored in age prediction. The small but
      statistically significant dependence of predicted age on cadaver length
      corresponds with the present strong secular increase in stature in the
      Netherlands. A concise catalogue with micrograph examples for every 10-year
      period in life is available upon request.

PMID- 16566755
TI  - A quantitative method for estimation of volume changes in arachnoid foveae with
      age.
AB  - Age-related changes of arachnoid foveae have been described, but objective,
      quantitative analyses are lacking. A new quantitative method is presented for
      estimation of change in total volume of arachnoid foveae with age. The pilot
      sample consisted of nine skulls from the Palmer Anatomy Laboratory. Arachnoid
      foveae were filled with sand, which was extracted using a vacuum pump. Mass was
      determined with an analytical balance and converted to volume. A reliability
      analysis was performed using intraclass correlation coefficients. The method was
      found to be highly reliable (intraobserver ICC = 0.9935, interobserver ICC =
      0.9878). The relationship between total volume and age was then examined in a
      sample of 63 males of accurately known age from the Hamann-Todd collection.
      Linear regression analysis revealed no statistically significant relationship
      between total volume and age, or foveae frequency and age (alpha = 0.05).
      Development of arachnoid foveae may be influenced by health factors, which could
      limit its usefulness in aging.

PMID- 16566756
TI  - Comparability of radiographic and 3D-ultrasound measurements of facial midline
      tissue depths.
AB  - As a second step in our three-dimensional (3D) ultrasound research on facial
      tissues, orthodontic patients with available lateral cephalographs (radiographs)
      allowing measurements of tissues along the midline of the face were recruited for
      ultrasound scanning. Comparison of three points on the upper lip (A-point), chin
      (B-point), and nose (nasion) produced differences of varying magnitude between
      radiographic and ultrasound measurements, with the B-point measurement being
      clearly affected by head orientation. Concordance was better for A-point and best
      for nasion. Although extension of two-dimensional (2D) ultrasound scanning of
      facial tissues to 3D scanning for forensic and surgical reconstructive purposes
      remains a worthy goal, it must be recognized that because of the differences in
      technique, measurements obtained from the different visualization modalities at
      present vary in their comparability.

PMID- 16566757
TI  - Test of an alternative method for determining sex from the os coxae: applications
      for modern Americans.
AB  - A recently proposed method for determining sex from the os coxae reports a 98%
      success rate using European collections. The purposes of the present study are to
      (1) evaluate the success rate of this proposed method using modern American os
      coxae from different population subgroups; (2) compare the success rate of the
      new method with that obtained using traditional techniques; and (3) determine
      replicability of the new method and interobserver error. Eight hundred and
      seventy-six adult left os coxae were independently evaluated by both authors.
      Summary statistics for sex classifications were calculated for the total sample
      and for a random sample of 400 individuals. The impact of sex and ancestry on the
      success of each method was calculated on the random sample using Pearson's chi2
      values. Results demonstrate that for modern American os coxae, neither sex nor
      race have a significant impact on the success rate for either the new or
      traditional methods (p < 0.01). Additionally, the success rate of the new method
      is comparable with that obtained using traditional techniques. Finally,
      interobserver error using the new method for overall sex determination is low.

PMID- 16566758
TI  - Genetics and genomics of core short tandem repeat loci used in human identity
      testing.
AB  - Over the past decade, the human identity testing community has settled on a set
      of core short tandem repeat (STR) loci that are widely used for DNA typing
      applications. A variety of commercial kits enable robust amplification of these
      core STR loci. A brief history is presented regarding the selection of core
      autosomal and Y-chromosomal STR markers. The physical location of each STR locus
      in the human genome is delineated and allele ranges and variants observed in
      human populations are summarized as are mutation rates observed from parentage
      testing. Internet resources for additional information on core STR loci are
      reviewed. Additional topics are also discussed, including potential linkage of
      STR loci to genetic disease-causing genes, probabilistic predictions of sample
      ethnicity, and desirable characteristics for additional STR loci that may be
      added in the future to the current core loci. These core STR loci, which form the
      basis for DNA databases worldwide, will continue to play an important role in
      forensic science for many years to come.

PMID- 16566759
TI  - Microchip-based cell lysis and DNA extraction from sperm cells for application to
      forensic analysis.
AB  - The current backlog of casework is among the most significant challenges facing
      crime laboratories at this time. While the development of next-generation
      microchip-based technology for expedited forensic casework analysis offers one
      solution to this problem, this will require the adaptation of manual, large
      volume, benchtop chemistry to small volume microfluidic devices. Analysis of
      evidentiary materials from rape kits where semen or sperm cells are commonly
      found represents a unique set of challenges for on-chip cell lysis and DNA
      extraction that must be addressed for successful application. The work presented
      here details the development of a microdevice capable of DNA extraction directly
      from sperm cells for application to the analysis of sexual assault evidence. A
      variety of chemical lysing agents are assessed for inclusion in the extraction
      protocol and a method for DNA purification from sperm cells is described.
      Suitability of the extracted DNA for short tandem repeat (STR) analysis is
      assessed and genetic profiles shown. Finally, on-chip cell lysis methods are
      evaluated, with results from fluorescence visualization of cell rupture and DNA
      extraction from an integrated cell lysis and purification with subsequent STR
      amplification presented. A method for on-chip cell lysis and DNA purification is
      described, with considerations toward inclusion in an integrated microdevice
      capable of both differential cell sorting and DNA extraction. The results of this
      work demonstrate the feasibility of incorporating microchip-based cell lysis and
      DNA extraction into forensic casework analysis.

PMID- 16566760
TI  - A proposal for standardization in forensic canine DNA typing: allele nomenclature
      of six canine-specific STR loci.
AB  - In this study a proposal for the allele nomenclature of six polymorphic short
      tandem repeat (STR) loci (PEZ3, PEZ6, PEZ8, PEZ10, FHC2161, and FHC2328) for
      canine genotyping (Canis lupus familiaris) is presented. The nomenclature is
      based on the sequence data of the polymorphic region of the microsatellite
      markers as recommended by the DNA commission of the International Society of
      Forensic Haemogenetics (ISFH) in 1994 for human DNA typing. To cover commonly and
      rarely occurring alleles, a selection of homozygous and heterozygous animals were
      analyzed and subjected to sequence studies. The alleles consisted of simple tri-
      and tetra-nucleotide repeat patterns as well as compound and highly complex
      repeat patterns. Several alleles revealing the same fragment size but different
      repeat structures were found. The allele designation described here was adopted
      to the number of repeats, including all variable regions within the amplified
      fragment. In a second step the most commonly occurring alleles were added to an
      allelic ladder for each marker allowing a reliable typing of all alleles
      differing in size. A total number of 142 unrelated dogs from surrounding
      municipal animal homes, private households, and canines in police duty were
      analyzed. The data were added to a population database providing allele
      frequencies for each marker.

PMID- 16566761
TI  - Three-dimensional surface topography acquisition and analysis for firearm
      identification.
AB  - In the last decade, computer-based systems for the comparison of microscopic
      firearms evidence have been the subject of considerable research work because of
      their expected capability of supporting the firearms examiner through the
      automated analysis of large amounts of evidence. The Integrated Ballistics
      Identification System, which is based on a two-dimensional representation of the
      specimen surface, has been widely adopted in forensic laboratories worldwide.
      More recently, some attempts to develop systems based on three-dimensional (3D)
      representations of the specimen surface have been made, both in the literature
      and as industrial products, such as BulletTRAX-3D, but fundamental limitations in
      achieving fully automated identification remain. This work analyzes the
      advantages and disadvantages of a 3D-based approach by proposing an approach and
      a prototype system for firearms evidence comparison that is based on the
      acquisition and analysis of the 3D surface topography of specimens, with
      particular reference to cartridge cases. The concept of 3D virtual comparison
      microscope is introduced, whose purpose is not to provide fully automated
      identification, but to show how the availability of 3D shape information can
      provide a whole new set of verification means, some of them being described and
      discussed in this work, specifically, visual enhancement tools and quantitative
      measurement of shape properties, for supporting, not replacing, the firearm
      examiner in reaching the final decision.

PMID- 16566762
TI  - Pyrotechnic reaction residue particle analysis.
AB  - Pyrotechnic reaction residue particle (PRRP) production, sampling and analysis
      are all very similar to that for primer gunshot residue. In both cases, the
      preferred method of analysis uses scanning electron microscopy to locate suspect
      particles and then uses energy dispersive x-ray spectroscopy to characterize the
      particle's constituent chemical elements. There are relatively few times when
      standard micro-analytical chemistry performed on pyrotechnic residues may not
      provide sufficient information for forensic investigators. However, on those
      occasions, PRRP analysis provides a greatly improved ability to discriminate
      between materials of pyrotechnic origin and other unrelated substances also
      present. The greater specificity of PRRP analysis is the result of its analyzing
      a large number of individual micron-sized particles, rather than producing only a
      single integrated result such as produced using standard micro-analytical
      chemistry. For example, PRRP analyses are used to demonstrate its ability to
      successfully (1) discriminate between pyrotechnic residues and unrelated
      background contamination, (2) identify that two different pyrotechnic
      compositions had previously been exploded within the same device, and (3)
      establish the chronology of an incident involving two separate and closely
      occurring explosions.

PMID- 16566764
TI  - Neutral heroin impurities from tetrahydrobenzylisoquinoline alkaloids.
AB  - Laudanosine, reticuline, codamine, and laudanine are members of the
      tetrahydrobenzylisoquinoline family of natural products. These alkaloids are
      present in the opium poppy, Papaver somniferum, and are subsequently found as
      impurities in clandestinely processed morphine. Morphine is then synthesized to
      heroin using hot acetic anhydride. During the course of this study, it was
      determined that these four tetrahydrobenzylisoquinolines undergo degradation to a
      series of 18 neutral impurities when subjected to hot acetic anhydride. Based on
      the degradation pathway, these new impurities were categorized into two sets of
      impurities called the C1-acetates compounds and the stilbene compounds.
      Synthesis, isolation, and structural elucidation information is provided for the
      tetrahydrobenzylisoquinoline alkaloids, and the new neutral impurities have been
      studied. Several hundred authentic heroin samples were analyzed using an
      established heroin signature program method. This methodology features the
      detection of trace neutral impurities present in heroin samples. It was
      determined that all 18 new impurities were detected in various quantities in four
      different types of heroin samples. Analytical results featuring these new
      impurities are reported for South American-, Southwest Asian-, Mexican-, and
      Southeast Asian-type heroin samples. These new impurities, coupled with other
      established forensic markers, enhance the ability to classify illicit heroin
      samples.

PMID- 16566763
TI  - The identification of the emulsifier component of emulsion explosives by liquid
      chromatography-mass spectrometry.
AB  - The widespread availability of emulsion explosives for commercial blasting has
      inevitably lead to their diversion for criminal misuse. Present techniques for
      the characterization of emulsion explosives and their residues is generally based
      on the detection and identification of the oxidizer and the hydrocarbon
      components. Use of these components is problematic for residue identification
      because ammonium nitrate, waxes, and oils are relatively common in the urban
      environment and even their co-detection does not exclude them being sourced from
      materials other than explosives. The detection of the emulsifier component offers
      increased evidential value as certain emulsifiers used in explosive formulations
      are manufactured for that specific use, or have limited environmental
      distribution. In the current study liquid chromatography-mass spectrometry (LC
      MS) was utilized for the characterization of two emulsifiers in common use;
      ethanolamine adducts of polyisobutylene succinic anhydride and sorbitol mono
      oleate (SMO). The LC-MS technique enabled the detection of both emulsifiers in
      preblast samples; however, only SMO was detected in postblast residues. The
      analysis of the hydrocarbon component by gas chromatography-mass spectrometry was
      achieved in the same procedure.

PMID- 16566765
TI  - GHB free acid: I. Solution formation studies and spectroscopic characterization
      by 1HNMR and FT-IR.
AB  - In forensic evidence, gamma-hydroxybutyric acid (GHB) has frequently been
      encountered in one of its salt forms (gamma-hydroxybutyrate), but has also been
      encountered in its free acid form (GHB). Owing to the physical properties,
      encounters of the free acid have been largely restricted to forensic exhibits
      comprising aqueous solutions, such as acidic beverages that have been "spiked" or
      formulated with GHB salts or gamma-butyrolactone (GBL). The analysis of GHB free
      acid presents particular difficulties including the potential for altering the
      original proportions of GHB free acid, GHB carboxylate, and GBL in the course of
      analysis, and discrimination between GHB free acid and carboxylate forms. In this
      work, the formation of GHB free acid in aqueous solutions (water and/or D2O) was
      studied as a function of solution pH. Proton nuclear magnetic resonance (1HNMR)
      and Fourier-transform infrared spectrometry (FT-IR) measurements were obtained on
      freshly prepared mixtures of NaGHB and HCl stock solutions representing a series
      of points along the GHB titration curve. Both 1HNMR and FT-IR were shown to track
      the changing proportions of GHB free acid and carboxylate forms as a function of
      pH, while simultaneously monitoring for the formation of the lactone (GBL). The
      results were consistent with acid-base conversion behavior for a carboxylic acid.
      1HNMR was shown to provide an ideal means for analysis of aqueous-based GHB/GBL
      forensic exhibits based on simple dilution of the neat liquid exhibit, without
      altering the original proportions of GHB free acid, carboxylate, and GBL in the
      samples.

PMID- 16566766
TI  - GHB free acid: II. Isolation and spectroscopic characterization for forensic
      analysis.
AB  - A reference standard for gamma-hydroxybutyric acid (GHB) free acid is not
      commercially available, making its analysis in forensic exhibits more difficult.
      GHB free acid is typically encountered in aqueous solution and in the presence of
      the lactone, gamma-butyrolactone (GBL), presenting difficulty in Fourier
      transform infrared (FT-IR) analysis. The strong infrared (IR) absorptivity of the
      GBL carbonyl band, the shifting of the GBL carbonyl band in aqueous solutions,
      and the position of the O-H bend for water can mask the main carbonyl band for
      GHB free acid. Model solutions of beta-hydroxybutyric acid (BHB) and GBL were
      studied in order to further understand the masking of the GHB free acid carbonyl
      band in FT-IR analysis. The use of second derivative FT-IR spectroscopy was shown
      to provide resolution of the free acid carbonyl band, and a presumptive test for
      GHB free acid was developed and applied. An extension of this work included
      preparing, for use as a standard reference material, small amounts (< or = 10 mg)
      of GHB free acid. Preparation was based on the instantaneous reaction of GHB's
      sodium salt with a stoichiometric amount of hydrochloric acid in aqueous
      solution, and subsequent isolation of the free acid in neat liquid form. Both FT
      IR and proton nuclear magnetic resonance spectra of the neat reference material
      were obtained and used to verify its identity. The isolation of GHB free acid
      from actual forensic exhibits is also presented, with identity confirmation using
      FT-IR.

PMID- 16566767
TI  - Color analysis of apparently achromatic automotive paints by visible
      microspectrophotometry.
AB  - Chromatic secondary pigments are utilized in achromatic automotive paints to
      create unique paint systems. These pigments may not be observable in reflected
      light; however, utilizing visible microspectrophotometry (MSP) discriminating
      data may be gathered. This study analyzed 160 apparently achromatic automotive
      paints via this technique for spectral evidence of secondary pigmentation. These
      results were compared with visual observations made via polarizing light
      microscopy. Positive spectral results were attained in approximately 25% of the
      black and gray/silver topcoat sample sets, whereas the white topcoat and gray
      undercoat set yielded no probative spectral data. The black sample set did yield
      several samples that produced spectral evidence of pigmentation when no visual
      chromatic data was observed. The results of this study suggest that paint
      analysis schemes should incorporate visible MSP for apparently achromatic black
      and gray/silver paint samples.

PMID- 16566768
TI  - Identification of a novel polymorphism in the X-chromosome region homologous to
      the DYS456 locus.
AB  - During an extensive multipopulation study with Y-short tandem repeat (STR) loci,
      amplified using the AmpFlSTR Yfiler PCR amplification kit, amplification of a 71
      bp fragment was observed in 2.32% of the male samples analyzed (N = 3141). By
      direct sequencing of this fragment, it was determined that the primer binding
      sequences were identical to those of the DYS456 locus. A T to G single-nucleotide
      polymorphism (SNP) enabled amplification of the 71 bp fragment. The SNP is
      located within an X-Y homologous region at Xq21.31 and was observed with the
      highest frequency within the African American and Sub-Saharan African populations
      in our study. Presence of SNP on the X chromosome did not interfere with the
      reliability of typing the DYS456 locus and the other Y-STR loci typeable using
      the AmpFlSTR Yfiler PCR amplification kit. Full profiles in a mixture of
      male:female at 1:4000 were obtained using the current configuration of the
      AmpFlSTR Yfiler kit even in the presence of female DNA containing the G variant.

PMID- 16566769
TI  - Probability of exclusion in paternity testing: time to reassess.
AB  - The average exclusion probability is a measure of efficiency in paternity
      testing; it refers to the a priori ability of a battery of tests to detect
      paternity inconsistencies. This parameter measures the capacity of the system to
      detect a false accusation of paternity. Traditionally, this average exclusion
      probability has been estimated as the probability of excluding a man who is not
      the father by an inconsistency in at least one of the studied loci. We suggest
      that this criterion should be corrected, as currently the presumed father is
      excluded when at least three genetic inconsistencies are found with the child
      being tested, not just one. This change of criterion has occurred because of the
      use of microsatellite loci, whose mutation rates are much greater than those of
      the coding genes used previously in paternity studies. We propose the use of the
      average probability of exclusion for at least three loci (not only one), as an
      honest measure of the combined probability of exclusion of several loci, and we
      propose an algebraic expression to calculate it.

PMID- 16566770
TI  - The application of miniplex primer sets in the analysis of degraded DNA from
      human skeletal remains.
AB  - A new set of multiplexed PCR primers has been applied to the analysis of human
      skeletal remains to determine their efficacy in analyzing degraded DNA. These
      primer sets, known as Miniplexes, produce shorter amplicons (50-280 base pairs
      (bp)) than standard short tandem repeat (STR) kits, but still utilize the 13
      CODIS STR loci, providing results that are searchable on national DNA databases.
      In this study, a set of 31 different human remains were exposed to a variety of
      environmental conditions, extracted, and amplified with commercial and Miniplex
      DNA typing kits. The amplification efficiency of the Miniplex sets was then
      compared with the Promega PowerPlex 16 system. Sixty-four percent of the samples
      generated full profiles when amplified with the Miniplexes, while only 16% of the
      samples generated full profiles with the Powerplex 16 kit. Complete profiles were
      obtained for 11 of the 12 Miniplex loci with amplicon sizes less than 200 bp.
      These data suggest smaller PCR amplicons may provide a useful alternative to
      mitochondrial DNA for anthropological and forensic analysis of degraded DNA from
      human skeletal remains.

PMID- 16566771
TI  - Minisequencing-based genotyping of Duffy and ABO blood groups for forensic
      purposes.
AB  - Duffy and ABO blood group genetic polymorphisms were studied by minisequencing
      analysis of single-nucleotide polymorphisms (SNPs) at nucleotide positions--33,
      125, 265, and 298 of the Duffy gene and at nucleotide positions-261, 297, 467,
      646, and 703 of the ABO gene. In an Italian population sample, we found four
      alleles and seven genotypes for the Duffy and six alleles and 16 genotypes for
      the ABO systems. The lower limit for reproducible results was 200 pg DNA, with a
      range of up to 10 ng and an optimum at 1 ng. All of the 16 analyzed inclusive
      paternity tests were also consistent with parentage and two out of four
      inconsistencies with parentage cases were excluded by one or more SNPs. Although
      Duffy and ABO SNP typing show lower informativeness than most current forensic
      tests, their robustness, the limited population distribution of FY* Fy type, and
      the sensitivity of the minisequencing technology suggest that these markers can
      be useful in selected forensic applications.

PMID- 16566772
TI  - The use of Polilight in the detection of seminal fluid, saliva, and bloodstains
      and comparison with conventional chemical-based screening tests.
AB  - Biological stains can be difficult to detect at crime scenes or on items
      recovered from crime scenes. The use of a versatile light source may assist in
      their detection. The ability of Polilight to locate potential semen, saliva, and
      blood stains on a range of substrates and at different dilutions was tested. We
      also tested the use of Polilight in comparison with conventional chemical-based
      presumptive screening tests such as acid phosphatase (AP), Phadebas, and luminol,
      often used in casework for detecting potential semen, saliva, and blood stains,
      respectively. The Polilight was able to locate stains that were not apparent to
      the naked eye. The color of the material on which a stain is deposited can have
      an effect on the detectibility of the stain. The Polilight was found to be
      comparable with the AP and Phadebas tests in terms of its sensitivity. In a
      comparative study between the AP test and Polilight on 40 casework exhibits, one
      false-negative result was observed when using the Polilight. On a series of mock
      casework exhibits it was determined that the Polilight can be used successfully
      to locate saliva stains for DNA analysis. The sensitivity of luminol for
      detecting potential bloodstains was greater than that of Polilight; however the
      Polilight has particular application in instances where a bloodstain may have
      been concealed with paint. Overall, the Polilight is a relatively safe, simple,
      noninvasive, and nondestructive technique suitable for use in forensic casework.

PMID- 16566773
TI  - Genetic variation in hemp and marijuana (Cannabis sativa L.) according to
      amplified fragment length polymorphisms.
AB  - Cannabis sativa L. (Cannabaceae) is one of the earliest known cultivated plants
      and is important in the global economy today as a licit and an illicit crop.
      Molecular markers distinguishing licit and illicit cultivars have forensic
      utility, but no direct comparison of hemp and marijuana amplified fragment length
      polymorphism (AFLP) has been made to date. Genetic variation was surveyed in
      three populations of fiber hemp and a potent cultivar of marijuana using AFLP
      markers. Ten primer pairs yielded 1206 bands, of which 88% were polymorphic.
      Eighteen bands represented fixed differences between all fiber populations and
      the drug cultivar. These markers have practical utility for (1) establishing
      conspiracy in the cultivation and distribution of marijuana, (2) identifying
      geographic sources of seized drugs, and (3) discriminating illegal, potent
      marijuana cultivars from hemp where the cultivation of industrial hemp is
      permitted.

PMID- 16566774
TI  - The analysis of illicit methaqualone containing preparations by gas
      chromatography-mass spectrometry for forensic purposes.
AB  - A validated gas chromatographic-mass spectrometric method for quantitative
      analysis of methaqualone (MTQ) in illicit preparations is reported. The method
      proved to have a coefficient of variation of below 5%. Four batches of seized
      tablets, two pairs with similar imprints, were analyzed. It was found that the
      average MTQ concentration in all four batches of tablets differed significantly
      (p = 0.01) rendering it impossible to conclude that, on the basis of MTQ
      concentration alone, the batches with a similar logo originated from the same
      manufacturer or manufacturing batch. Conversely, it can be said that in this
      case, the four batches originated from either different clandestine laboratories
      or manufacturing batches.

PMID- 16566775
TI  - Comparison of handmarks in manual strangulation: an experimental study.
AB  - A police case with a strangulated woman with fingermarks on the neck and two
      suspects identifying each other as the perpetrator set off a laboratory
      experiment. Twenty-one males participated in the study. Blue paint was applied to
      their fingers, after which they grasped a neck dummy and pressed hard as if
      strangulating someone. The imprint was removed from the dummy, and their hands
      were photographed. Five imprints were randomly chosen and superimposed on the
      hand photographs in blind trials. In no cases did we match an imprint to the
      correct hand. However, in four cases we matched the imprint with several hands,
      one of which was the correct one. This means we were able to exclude nonmatches
      in 4/5 cases. Overall, matching of hands and fingermarks is difficult and
      inconclusive. Objective criteria for matching are difficult to establish, and
      matching is probably best suited for cases with specific anatomical features.

PMID- 16566776
TI  - Missing persons-missing data: the need to collect antemortem dental records of
      missing persons.
AB  - The subject of missing persons is of great concern to the community with numerous
      associated emotional, financial, and health costs. This paper examines the
      forensic medical issues raised by the delayed identification of individuals
      classified as "missing" and highlights the importance of including dental data in
      the investigation of missing persons. Focusing on Australia, the current
      approaches employed in missing persons investigations are outlined. Of particular
      significance is the fact that each of the eight Australian states and territories
      has its own Missing Persons Unit that operates within distinct state and
      territory legislation. Consequently, there is a lack of uniformity within
      Australia about the legal and procedural framework within which investigations of
      missing persons are conducted, and the interaction of that framework with
      coronial law procedures. One of the main investigative problems in missing
      persons investigations is the lack of forensic medical, particularly,
      odontological input. Forensic odontology has been employed in numerous cases in
      Australia where identity is unknown or uncertain because of remains being
      skeletonized, incinerated, or partly burnt. The routine employment of the
      forensic odontologist to assist in missing person inquiries, has however, been
      ignored. The failure to routinely employ forensic odontology in missing persons
      inquiries has resulted in numerous delays in identification. Three Australian
      cases are presented where the investigation of individuals whose identity was
      uncertain or unknown was prolonged due to the failure to utilize the appropriate
      (and available) dental resources. In light of the outcomes of these cases, we
      suggest that a national missing persons dental records database be established
      for future missing persons investigations. Such a database could be easily
      managed between a coronial system and a forensic medical institute. In Australia,
      a national missing persons dental records database could be incorporated into the
      National Coroners Information System (NCIS) managed, on behalf of Australia's
      Coroners, by the Victorian Institute of Forensic Medicine. The existence of the
      NCIS would ensure operational collaboration in the implementation of the system
      and cost savings to Australian policing agencies involved in missing person
      inquiries. The implementation of such a database would facilitate timely and
      efficient reconciliation of clinical and postmortem dental records and have
      subsequent social and financial benefits.

PMID- 16566778
TI  - Pediatric homicides related to burn injury: a retrospective review at the medical
      university of South Carolina.
AB  - Many burn injuries are mistakenly referred to as "accidents" because they occur
      suddenly and seem unpredictable and uncontrollable; however, injuries often occur
      in predictable patterns. We reviewed all pediatric forensic cases referred to the
      Medical University of South Carolina Forensic Pathology Section over a 28-year
      period from January 1975 to December 2002. There were 124 cases with 121 fire
      related fatalities and three scald fatalities. Ninety of the burn victims were in
      the 0-5-year age group. The manner of deaths showed 108 accidents and 12
      homicides (four undetermined). Eleven of 12 burn-related homicides occurred at
      the home with all of the victims in the 1-8-year age group. The perpetrator of
      the home fire homicides was the mother in five cases and the sister in one case
      (two undetermined). Homicide involved a vehicle fire in one case in which the
      father caused an explosion with an accelerant. The three scald death perpetrators
      were the father, mother's boyfriend, and an aunt.This retrospective study and
      review of the literature may reveal patterns useful for evaluation of manner of
      death. By recognizing scene characteristics, potential perpetrators, and children
      at risk, we can better classify pediatric burn-related fatalities.

PMID- 16566777
TI  - Esophageal causes of sudden and unexpected death.
AB  - Gastrointestinal conditions are uncommon causes of sudden and/or unexpected death
      as compared to cardiovascular diseases, motor vehicle trauma, or suicide, and may
      involve an array of fatal mechanisms. Lethal esophageal conditions are
      encountered even less often, the manifestations of which include acute upper
      airway occlusion from tumors or foreign material, intraluminal hemorrhage from
      vascular abnormalities, or perforation with fistula formation resulting in
      hemorrhage and sepsis. When encountered at autopsy, a particular condition may
      also be a manifestation of a disease that does not primarily involve the
      esophagus. For this reason, a detailed autopsy investigation is required for
      evidence of systemic or remote disease when lesions are found within the
      esophagus. In this report, possible life-threatening esophageal conditions are
      reviewed with a description of lethal mechanisms, mention of rare associated
      diseases, and comment on difficulties that may arise at autopsy in the evaluation
      of such cases.

PMID- 16566779
TI  - Sudden death due to an unrecognized cardiac hydatid cyst: three medicolegal
      autopsy cases.
AB  - Echinococcosis is a human infection caused by the larval stage of Echinococcocus
      granulosus. The most common sites of infection are the liver and the lungs.
      Cardiac hydatid cysts are very rare, even in regions where hydatic cysts are
      endemic (the Mediterranean, South America, Africa, and Australia). It has been
      reported that cardiac involvement is seen in about 0.5-3% of human echinococcosis
      cases. Three cases of cardiac hydatid disease that caused sudden death and which
      were histopathologically diagnosed are reported. Cardiac echinococcosis is rare,
      but due to its insidious presentation and affinity to cause sudden death, it is
      important that it be identified in the histopathological examination.

PMID- 16566780
TI  - Fatal dog maulings associated with infant swings.
AB  - We present three cases of fatal dog maulings of infants placed in mobile infant
      swings, a phenomenon not previously described in the literature. In each case,
      the victim was left in a mobile swing, unsupervised by an adult, and the
      attacking dog was a family pet. Case 1 involved an 18-day-old male infant
      attacked by a pit bull; Case 2 involved a 3-month-old male infant attacked by a
      Chow Chow and/or a Dachshund, and Case 3 involved an 18-day-old female infant
      attacked by a Labrador-pit bull mix. These cases not only underscore the
      importance of not leaving young children unattended in the presence of pet dogs,
      but also raise the possibility that mobile swings may trigger a predatory
      response in dogs and thus may represent an additional risk factor for dog attack.

PMID- 16566781
TI  - Abusive prescription of psychostimulants: a study of two cases.
AB  - Because psychostimulants have serious possible side effects and particular
      potential for abuse, their therapeutic indications are today exclusively limited
      to disorders such as obesity, narcolepsy, or attention deficit/hyperactivity
      disorder. We report two cases of abusive prescription of these drugs. The first
      concerns a woman who was treated for a 3 kg weight gain with fenproporex for 5
      years and presented a withdrawal syndrome when this drug was no longer marketed
      in France. In the second case, a woman who complained of atypical sleep problems
      was prescribed modafinil, methylphenidate, clobazam, lormetazepam, meprobamate,
      and aceprometazine, and was found dead in her home a few weeks later in
      unexplained circumstances. For these two patients, neither the indications, nor
      the contraindications, nor the prescribing rules for these restricted drugs had
      been complied with. This case report highlights the extreme danger of these
      substances and stresses the importance of adhering to the rules of prescription.

PMID- 16566782
TI  - Suicide associated with the Antichrist delusion.
AB  - The Antichrist delusion is a relatively infrequently observed religious delusion.
      Some cases of the Antichrist delusion have been associated with violence toward
      others. The aim of this article is to document a case of suicide secondary to the
      delusion. At age 17 a woman with no history of mental illness developed the
      belief that she was the Antichrist. For several years she did not discuss this
      with anyone and functioned appropriately in society. Then, at age 32, after the
      birth of her first child, her delusion intensified and she ultimately committed
      suicide to protect others from the harm she felt she was destined to cause them.
      The Antichrist delusion as a misidentification state may involve danger to a
      patient who harbors the delusion, as well as to other individuals.

PMID- 16566783
TI  - The influence of site of collection on postmortem morphine concentrations in
      heroin overdose victims.
AB  - When assaying for postmortem morphine concentration, significant site sampling
      variability exists between central and peripheral sampling sites and even within
      sampling regions of the body. To study the variation, 76 suspected heroin
      overdoses were identified. Each had femoral artery (FA) and vein (FV), left and
      right ventricle and pooled heart blood samples obtained at autopsy. Forty-four
      tested positive for morphine. Morphine concentrations were determined by gas
      chromatography/mass spectrometry, with sampling site differences reported as log
      transformed ratios and compared by signed rank test. The mean FA to FV ratio for
      total morphine was 1.2 (range 0-4.5). The ratio for left heart to right heart
      total morphine was 1.1 (range 0.4-3.2). Left ventricular to FV total morphine
      ratio was 2.0 (range 0.6-6.9). In these opioid overdose deaths, FA and FV
      morphine concentrations are usually similar, although up to 4.5-fold differences
      were noted. Centrally obtained morphine concentrations are on average twice as
      high compared with peripheral morphine concentrations. Left and right ventricular
      morphine concentrations were usually similar, although up to 3.2-fold differences
      were noted (left side higher).

PMID- 16566784
TI  - Relationships between concentrations of cocaine and its hydrolysates in
      peripheral blood, heart blood, vitreous humor and urine.
AB  - Cocaine is known to degrade in vivo and in vitro by several hydrolytic
      mechanisms. A previous study found that the initial amount of cocaine added to
      plasma could be accounted for by summing the molar concentrations of cocaine's
      hydrolysis products and the cocaine remaining after hydrolysis. The present study
      was undertaken to investigate whether or not relationships might exist between
      such molar concentration sums for different postmortem bodily fluids.
      Determinations of cocaine, benzoylecgonine, ecgonine methyl ester, and ecgonine
      were performed using liquid chromatography/mass spectrometry (LC/MS/MS) with
      heart blood, femoral blood, vitreous humor (VH), and urine (UR). The results
      demonstrate a strong correlation between blood and VH concentrations (correlation
      coefficients of 0.88-0.94), weak correlation between the UR and blood
      concentrations (correlation coefficients of 0.61-0.64), and weak correlation
      between UR and VH concentrations (correlation coefficient of 0.59). The results
      demonstrate that ecgonine is a significant hydrolysate with concentrations on the
      same order of magnitude as benzoylecgonine. The results are consistent with rapid
      distribution of the parent drug and its hydrolysates in the blood and VH. The
      strong correlation between the blood and VH demonstrates that VH is an important
      medium for toxicology testing when attempting to make a determination of cocaine
      intoxication.

PMID- 16566786
TI  - Commentary on: Alexander RT, Radisch D. Sudden infant death syndrome risk factors
      with regards to sleep position, sleep surface, and co-sleeping. J Forensic Sci
      2005;50:1-5.

PMID- 16566792
TI  - Allele frequency data for 19 short tandem repeats (PowerPlex 16 and FFFl) in a
      Belgian population sample.

PMID- 16566791
TI  - Allele frequencies of penta D and penta E loci in Afghanistan population.

PMID- 16566793
TI  - Genetic variation for penta D and penta E in a northeast Colombian population
      (Department of Santander).

PMID- 16566794
TI  - Population data on eight short tandem repeat loci in the Barbadian population.

PMID- 16566795
TI  - Population genetic analysis of Moroccans residing in Belgium using 15 STRs of the
      Identifiler kit.

PMID- 16566796
TI  - Allele frequency distribution of short tandem repeat D13S1493 in two populations.

PMID- 16566797
TI  - Supplemented data on mutation rates in 33 autosomal short tandem repeat
      polymorphisms.

PMID- 16566798
TI  - Distribution of D9S2150, GATA164F07, and D10S2469 alleles in a Chinese population
      sample.

PMID- 16566799
TI  - Polymorphism of three short tandem repeat loci in Chinese population.

PMID- 16566800
TI  - Genetic variation for 15 short tandem repeat loci in an El Salvadoran (Central
      America) population.

PMID- 16566809
TI  - Abstracts of the 46th Annual Scientific Meeting of the British Society for
      Haematology incorporating the Netherlands and British Haemostasis and Thrombosis
      Societies, 3-5 April 2006, Edinburgh, United Kingdom.

PMID- 16566811
TI  - Using prostate-specific antigen screening and nomograms to assess risk and
      predict outcomes in the management of prostate cancer.
AB  - We review the role of prostate-specific antigen (PSA) and the importance of
      patient education in the management of prostate cancer, based on discussions held
      at a European symposium on managing prostate cancer. Although PSA is the most
      widely used serum marker for detecting prostate cancer and for monitoring
      treatment responses, its use as a diagnostic marker is controversial due to
      concerns of over-diagnosis and low specificity. PSA isoforms, as well as PSA
      doubling time, might improve the specificity for earlier prostate cancer
      detection and can be used as surrogate markers for treatment efficacy. Patients
      can differ considerably in the importance they place on health-related quality of
      life aspects and fear of cancer progression. Consequently, there needs to be
      active, educated discussion of risk and outcomes between physicians and patients.
      Risk assessment tools, e.g. validated nomograms, enable clinicians to improve
      their decision analysis and form the basis for subsequent discussion of treatment
      options between the physician and patient, thereby enabling informed consent and
      appropriate decision-making.

PMID- 16566812
TI  - Optimizing outcomes and quality of life in the hormonal treatment of prostate
      cancer.
AB  - We review the effectiveness of androgen-deprivation therapy (ADT) in the
      management of prostate cancer, and the effect that this treatment has on a
      patient's quality of life (QoL), based on discussions held at a European
      symposium on the management of prostate cancer. The overall QoL is reduced in
      asymptomatic men, and there are known decreases in cognitive function, self
      esteem, libido and sexual function. Hot flashes are also a frequent problem.
      Prolonged ADT can lead to osteoporosis and subsequently fractures. Various
      effective methods exist to manage and minimize these side-effects; some are
      specific to the side-effect, whereas other more general methods include lifestyle
      changes, specific drugs and added hormonal manipulations. Intermittent ADT for
      patients taking luteinizing hormone-releasing hormone agonists offers a promising
      method to reduce adverse effects, and possibly increases the time to androgen
      independence. Initial studies indicate that prostate-specific antigen-based
      progression with intermittent ADT is similar to that seen with continuous ADT,
      but there is a reduction in side-effects, leading to an improvement in QoL.

PMID- 16566813
TI  - A re-staging transurethral resection predicts early progression of superficial
      bladder cancer.
AB  - OBJECTIVE: To determine whether pathology on a re-staging transurethral resection
      (TUR) predicts the early progression of superficial bladder cancer. PATIENTS AND
      METHODS: In all, 710 patients presenting with multiple superficial bladder
      cancers were evaluated by re-staging TUR and followed for 5 years. Tumours were
      classified by stage as confined to mucosa (Ta) or invading submucosa (T1), and by
      grade (low- or high-grade). Pathology on re-staging TUR was correlated with the
      endpoints of tumour recurrence and stage progression. RESULTS: Of the 710
      patients, 490 (69%) had a recurrence and 149 (21%) progressed over 5 years.
      Eighty patients had high-grade invasive (T1G3) cancer on re-staging TUR and 61
      (76%) progressed to muscle invasion (median time to progression 15 months),
      compared with 88 of 630 (14%) who had no evidence of tumour (T0) or other than T1
      tumours detected on re-staging TUR. CONCLUSION: A re-staging TUR identifies
      patients with superficial bladder cancer who are at high risk of early tumour
      progression.

PMID- 16566814
TI  - The value of a second transurethral resection for T1 bladder cancer.
AB  - OBJECTIVE: To evaluate a series of repeat transurethral resections (TURs) of
      tumour in patients with T1 bladder cancer, usually used to ensure a complete
      resection and to exclude the possibility muscle-invasive disease. PATIENTS AND
      METHODS: In all, 136 consecutive patients had a second TUR because of a
      histopathological diagnosis of T1 transitional cell carcinoma (TCC) after their
      initial TUR. Of the 136 patients, 101 were first presentations and 35 had
      recurrent tumours. The second TUR was done 4-6 weeks later. The evaluation
      included the presence of previously undetected residual tumour, changes to
      histopathological staging/grading, and tumour location. RESULTS: In all, 71
      patients (52%) had residual disease according to findings from specimens obtained
      during the second TUR. The staging was: no tumour, 65 (48%); Ta, 11 (8%); T1, 32
      (24%); Tis, 15 (11%); and > or = T2, 13 (10%). Histopathological changes that
      worsened the prognosis (>T1 and or concomitant Tis) were found in 21% of
      patients. Residual malignant tissue was found in the same location as the first
      TUR in 86% of the patients, and at different locations in 14%. Overall, 28
      patients (21% of the original 136) had a radical cystectomy as a consequence of
      the second TUR findings. CONCLUSIONS: A routine second TUR should be advised in
      patients with T1 TCC of the bladder, to achieve a more complete tumour resection
      and to identify patients who should have a prompt cystectomy.

PMID- 16566815
TI  - The impact of fathers' physical and psychosocial work conditions on attempted and
      completed suicide among their children.
AB  - BACKGROUND: Adverse employment experiences, particularly exposure to unemployment
      and the threat of unemployment, have been strongly associated with several
      adverse mental and physical health outcomes including suicide. However, virtually
      no research has been conducted on the trans-generational impact of parental
      working conditions on attempted or completed suicide among their children.
      METHODS: We conducted a nested case control study based on a cohort, gathered in
      the western Canadian province of British Columbia, of male sawmill workers and a
      second cohort of their children. Physical and psychosocial work conditions to
      which fathers were exposed during the first 16 years of their children's lives,
      measured using the demand/control model, were linked to hospital suicide records
      (attempted and completed) among their children. RESULTS: Two hundred and fifty
      children in the cohort attempted or committed suicide between 1985 and 2001.
      Multivariate models, with partial control for father's mental health outcomes
      prior to their child's suicide demonstrate, 1) a strong association between low
      duration of father's employment at a study sawmill and attempted suicide for
      their male children, 2) elevated odds for attempted suicide among female children
      of fathers' employed in a sawmill job with low control and, 3) a strong
      association between fathers in jobs with low psychological demand and completed
      suicides among male children. CONCLUSION: Exposure of fathers to adverse
      psychosocial work conditions during the first 16 years of their children's life
      was associated with greater odds for attempted and completed suicide among their
      children.

PMID- 16566816
TI  - First CytoJournal Peer-Reviewer's Retreat in 2006 - open access, peer-review, and
      impact factor.
AB  - CytoJournal organized its first Peer-Reviewer's Retreat of 2006 during the United
      States and Canadian Academy of Pathology Annual Meeting at Atlanta on Feb 12,
      2006. The major topics discussed were open access, peer review, and impact
      factors. Representative participants volunteered to join the task force to
      prepare an instructional guide for peer-reviewing cytopathology manuscripts.
      Concern about the impact factor for CytoJournal was discussed. A feedback to its
      readers and authors was recommended. Impact factor calculation needs at least
      three years of journal statistics. It is only possible after two years from the
      time a journal is first accepted by Thomson-ISI for citation tracking.
      CytoJournal is still too new for an impact factor to be calculated. However,
      general progress of CytoJournal suggests an encouraging pattern for high impact
      factor.

PMID- 16566818
TI  - Technical efficiency of district hospitals: evidence from Namibia using data
      envelopment analysis.
AB  - BACKGROUND: In most countries of the sub-Saharan Africa, health care needs have
      been increasing due to emerging and re-emerging health problems. However, the
      supply of health care resources to address the problems has been continuously
      declining, thus jeopardizing the progress towards achieving the health-related
      Millennium Development Goals. Namibia is no exception to this. It is therefore
      necessary to quantify the level of technical inefficiency in the countries so as
      to alert policy makers of the potential resource gains to the health system if
      the hospitals that absorb a lion's share of the available resources are
      technically efficient. METHOD: All public sector hospitals (N = 30) were included
      in the study. Hospital capacity utilization ratios and the data envelopment
      analysis (DEA) technique were used to assess technical efficiency. The DEA model
      used three inputs and two outputs. Data for four financial years (1997/98 to
      2000/2001) was used for the analysis. To test for the robustness of the DEA
      technical efficiency scores the Jackknife analysis was used. RESULTS: The
      findings suggest the presence of substantial degree of pure technical and scale
      inefficiency. The average technical efficiency level during the given period was
      less than 75%. Less than half of the hospitals included in the study were located
      on the technically efficient frontier. Increasing returns to scale is observed to
      be the predominant form of scale inefficiency. CONCLUSION: It is concluded that
      the existing level of pure technical and scale inefficiency of the district
      hospitals is considerably high and may negatively affect the government's
      initiatives to improve access to quality health care and scaling up of
      interventions that are necessary to achieve the health-related Millennium
      Development Goals. It is recommended that the inefficient hospitals learn from
      their efficient peers identified by the DEA model so as to improve the overall
      performance of the health system.

PMID- 16566817
TI  - Exploring the reasons for the large density of triplex-forming oligonucleotide
      target sequences in the human regulatory regions.
AB  - BACKGROUND: DNA duplex sequences that can be targets for triplex formation are
      highly over-represented in the human genome, especially in regulatory regions.
      RESULTS: Here we studied using bioinformatics tools several properties of triplex
      target sequences in an attempt to determine those that make these sequences so
      special in the genome. CONCLUSION: Our results strongly suggest that the unique
      physical properties of these sequences make them particularly suitable as
      "separators" between protein-recognition sites in the promoter region.

PMID- 16566819
TI  - The yin and yang of 15-lipoxygenase-1 and delta-desaturases: dietary omega-6
      linoleic acid metabolic pathway in prostate.
AB  - One of the major components in high-fat diets (Western diet) is the omega (omega,
      n)-6 polyunsaturated fatty acid (PUFA) called linoleic acid (LA). Linoleic acid
      is the precursor for arachidonic acid (AA). These fatty acids are metabolized to
      an array of eicosanoids and prostaglandins depending upon the enzymes in the
      pathway. Aberrant expression of the catabolic enzymes such as cyclooxygenases
      (COX-1 and/or -2) or lipoxygenases (5-LO, 12-LO, 15-LO-1, and 15-LO-2) that
      convert PUFA either AA and/or LA to bioactive lipid metabolites appear to
      significantly contribute to the development of PCa. However, PUFA and its
      cellular interactions in PCa are poorly understood. We therefore examined the
      mRNA levels of key enzymes involved in the LA and AA pathways in 18 human donor
      (normal) prostates compared to 60 prostate tumors using the Affymetrix U95Av2
      chips. This comparative (normal donor versus prostate cancer) study showed that:
      1) the level of 15-LO-1 expression (the key enzyme in the LA pathway) is low (P <
      0.001), whereas the levels of delta-5 desaturase (P < 0.001, the key enzyme in
      the AA pathway), delta-6 desaturase (P = 0.001), elongase (P = 0.16) and 15
      lipoxygenase-2 (15-LO-2, P = 0.74) are higher in donor (normal) prostates, and 2)
      Contrary to the observation in the normal tissues, significantly high levels of
      only 15-LO-1; whereas low levels of delta-6 desaturase, elongase, delta-5
      desaturase and 15-LO-2 respectively, were observed in PCa tissues. Although the
      cyclooxygenase (COX)-1 and COX-2 mRNA levels were high in PCa, no significant
      differences were observed when compared in donor tissues. Our study underscores
      the importance of promising dietary intervention agents such as the omega-3 fatty
      acids as substrate competitors of LA/AA, aimed primarily at high 15-LO-1 and COX
      2 as the molecular targets in PCa initiation and/or progression.

PMID- 16566820
TI  - Identification and characterization of human polyserase-3, a novel protein with
      tandem serine-protease domains in the same polypeptide chain.
AB  - BACKGROUND: We have previously described the identification and characterization
      of polyserase-1 and polyserase-2, two human serine proteases containing three
      different catalytic domains within the same polypeptide chain. Polyserase-1 shows
      a complex organization and it is synthesized as a membrane-bound protein which
      can generate three independent serine protease domains as a consequence of post
      translational processing events. The two first domains are enzymatically active.
      By contrast, polyserase-2 is an extracellular glycosylated protein whose three
      protease domains remain embedded in the same chain, and only the first domain
      possesses catalytic activity. RESULTS: Following our interest in the study of the
      human degradome, we have cloned a human liver cDNA encoding polyserase-3, a new
      protease with tandem serine protease domains in the same polypeptide chain.
      Comparative analysis of polyserase-3 with the two human polyserases described to
      date, revealed that this novel polyprotein is more closely related to polyserase
      2 than to polyserase-1. Thus, polyserase-3 is a secreted protein such as
      polyserase-2, but lacks additional domains like the type II transmembrane motif
      and the low-density lipoprotein receptor module present in the membrane-anchored
      polyserase-1. Moreover, analysis of post-translational mechanisms operating in
      polyserase-3 maturation showed that its two protease domains remain as integral
      parts of the same polypeptide chain. This situation is similar to that observed
      in polyserase-2, but distinct from polyserase-1 whose protease domains are
      proteolytically released from the original chain to generate independent units.
      Immunolocalization studies indicated that polyserase-3 is secreted as a non
      glycosylated protein, thus being also distinct from polyserase-2, which is a
      heavily glycosylated protein. Enzymatic assays indicated that recombinant
      polyserase-3 degrades the alpha-chain of fibrinogen as well as pro-urokinase-type
      plasminogen activator (pro-uPA). Northern blot analysis showed that polyserase-3
      exhibits a unique expression pattern among human polyserases, being predominantly
      detected in testis, liver, heart and ovary, as well as in several tumor cell
      lines. CONCLUSION: These findings contribute to define the growing group of human
      polyserine proteases composed at present by three different proteins. All of them
      share a complex structural design with several catalytic units in a single
      polypeptide but also show specific features in terms of enzymatic properties,
      expression patterns and post-translational maturation mechanisms.

PMID- 16566821
TI  - Health-related quality of life of irritable bowel syndrome patients in different
      cultural settings.
AB  - BACKGROUND: Persons with Irritable bowel syndrome (IBS) are seriously affected in
      their everyday life. The effect across different cultural settings of IBS on
      their quality of life has been little studied. The aim was to compare health
      related quality of life (HRQOL) of individuals suffering from IBS in two
      different cultural settings; Crete, Greece and Linkoping, Sweden. METHODS: This
      study is a sex and age-matched case-control study, with n = 30 Cretan IBS cases
      and n = 90 Swedish IBS cases and a Swedish control group (n = 300) randomly
      selected from the general population. Health-related quality of life, measured by
      SF-36 and demographics, life style indicators and co-morbidity, was measured.
      RESULTS: Cretan IBS cases reported lower HRQOL on most dimensions of SF-36 in
      comparison to the Swedish IBS cases. Significant differences were found for the
      dimensions mental health (p < 0.0001) and general health (p = 0.05) even after
      adjustments for educational level and co-morbidity. Women from Crete with IBS
      scored especially low on the dimensions general health (p = 0.009) and mental
      health (p < 0.0001) in comparison with Swedish women with IBS. The IBS cases,
      from both sites, reported significantly lower scores on all HRQOL dimensions in
      comparison with the Swedish control group. CONCLUSION: The results from this
      study tentatively support that the claim that similar individuals having the same
      disease, e.g. IBS, but living in different cultural environments could perceive
      their disease differently and that the disease might affect their everyday life
      and quality of life in a different way. The Cretan population, and especially
      women, are more seriously affected mentally by their disease than Swedish IBS
      cases. Coping with IBS in everyday life might be more problematic in the Cretan
      environment than in the Swedish setting.

PMID- 16566822
TI  - Demand of elderly people for residential care: an exploratory study.
AB  - BACKGROUND: Because of the rapid aging population, the demand for residential
      care exceeds availability. This paper presents the results of a study that
      focuses on the demand of elderly people for residential care and determinants
      (elderly people's personal characteristics, needs and resources) that are
      associated with this demand. Furthermore, the accuracy of the waiting list as a
      reflection of this demand has been examined. METHODS: 67 elderly people waiting
      for admission into a home for the elderly, are subjected to semi-structured
      interviews. The data are analyzed by using multivariate statistics. RESULTS:
      Elderly people who indicate that they would refuse an offer of admission into a
      home for the elderly feel healthier (p = 0.02), have greater self-care agency (p
      = 0.02) and perceive less necessity of admission (p < 0.01), compared to those
      who would accept such an offer. Especially the inability to manage everyday
      activities and the lack of a social network are highly associated with the
      elderly people's demand for residential care. Furthermore, it is evident that
      waiting lists for homes for the elderly do not accurately reflect the demand for
      residential care, since 35% of the elderly people on a waiting list did not
      actually experience an immediate demand for residential care and stated that they
      would not accept an offer of admission. Quite a lot of respondents just
      registered out of a sense of precaution; a strategic decision dictated by current
      shortages in care provision and a vulnerable health status. CONCLUSION: The
      results contribute to the understanding of waiting lists and the demand for
      residential care. It became apparent that not everybody who asks for admission
      into a home for the elderly, really needed it. The importance of elderly people's
      resources like social networks and the ability to manage everyday activities in
      relation to the demand for care became clear. These findings are important
      because they indicate that resources also play a role in predicting elderly
      people's demand and as a result can guide the development and the (re)design of
      adequate health care services.

PMID- 16566823
TI  - Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell
      death in the mouse MPTP model of Parkinson's disease.
AB  - BACKGROUND: Accumulating evidence suggests that inflammation plays an important
      role in the progression of Parkinson's disease (PD). Among many inflammatory
      factors found in the PD brain, cyclooxygenase (COX), specifically the inducible
      isoform, COX-2, is believed to be a critical enzyme in the inflammatory response.
      Induction of COX-2 is also found in an experimental model of PD produced by
      administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). METHOD: COX
      2-deficient mice or C57BL/6 mice were treated with MPTP to investigate the
      effects of COX-2 deficiency or by using various doses of valdecoxib, a specific
      COX-2 inhibitor, which induces inhibition of COX-2 on dopaminergic neuronal
      toxicity and locomotor activity impairment. Immunohistochemistry, stereological
      cell counts, immunoblotting, an automated spontaneous locomotor activity recorder
      and rotarod behavioral testing apparatus were used to assess microglial
      activation, cell loss, and behavioral impairments. RESULTS: MPTP reduced tyrosine
      hydroxylase (TH)-positive cell counts in the substantia nigra pars compacta
      (SNpc); total distance traveled, vertical activity, and coordination on a
      rotarod; and increased microglia activation. Valdecoxib alleviated the microglial
      activation, the loss of TH-positive cells and the decrease in open field and
      vertical activity. COX-2 deficiency attenuated MPTP-induced microglial
      activation, degeneration of TH-positive cells, and loss of coordination.
      CONCLUSION: These results indicate that reducing COX-2 activity can mitigate the
      secondary and progressive loss of dopaminergic neurons as well as the motor
      deficits induced by MPTP, possibly by suppression of microglial activation in the
      SNpc.

PMID- 16566825
TI  - The time-profile of cell growth in fission yeast: model selection criteria
      favoring bilinear models over exponential ones.
AB  - BACKGROUND: There is considerable controversy concerning the exact growth profile
      of size parameters during the cell cycle. Linear, exponential and bilinear models
      are commonly considered, and the same model may not apply for all species.
      Selection of the most adequate model to describe a given data-set requires the
      use of quantitative model selection criteria, such as the partial (sequential) F
      test, the Akaike information criterion and the Schwarz Bayesian information
      criterion, which are suitable for comparing differently parameterized models in
      terms of the quality and robustness of the fit but have not yet been used in cell
      growth-profile studies. RESULTS: Length increase data from representative
      individual fission yeast (Schizosaccharomyces pombe) cells measured on time-lapse
      films have been reanalyzed using these model selection criteria. To fit the data,
      an extended version of a recently introduced linearized biexponential (LinBiExp)
      model was developed, which makes possible a smooth, continuously differentiable
      transition between two linear segments and, hence, allows fully parametrized
      bilinear fittings. Despite relatively small differences, essentially all the
      quantitative selection criteria considered here indicated that the bilinear model
      was somewhat more adequate than the exponential model for fitting these fission
      yeast data. CONCLUSION: A general quantitative framework was introduced to judge
      the adequacy of bilinear versus exponential models in the description of growth
      time-profiles. For single cell growth, because of the relatively limited data
      range, the statistical evidence is not strong enough to favor one model clearly
      over the other and to settle the bilinear versus exponential dispute.
      Nevertheless, for the present individual cell growth data for fission yeast, the
      bilinear model seems more adequate according to all metrics, especially in the
      case of wee1Delta cells.

PMID- 16566824
TI  - GENOMEMASKER package for designing unique genomic PCR primers.
AB  - BACKGROUND: The design of oligonucleotides and PCR primers for studying large
      genomes is complicated by the redundancy of sequences. The eukaryotic genomes are
      particularly difficult to study due to abundant repeats. The speed of most
      existing primer evaluation programs is not sufficient for large-scale
      experiments. RESULTS: In order to improve the efficiency and success rate of
      automatic primer/oligo design, we created a novel method which allows rapid
      masking of repeats in large sequence files, for example in eukaryotic genomes. It
      also allows the detection of all alternative binding sites of PCR primers and the
      prediction of PCR products. The new method was implemented in a collection of
      efficient programs, the GENOMEMASKER package. The performance of the programs was
      compared to other similar programs. We also modified the PRIMER3 program, to be
      able to design primers from lowercase-masked sequences. CONCLUSION: The
      GENOMEMASKER package is able to mask the entire human genome for non-unique
      primers within 6 hours and find locations of all binding sites for 10,000
      designed primer pairs within 10 minutes. Additionally, it predicts all
      alternative PCR products from large genomes for given primer pairs.

PMID- 16566826
TI  - The chemopreventive properties of chlorogenic acid reveal a potential new role
      for the microsomal glucose-6-phosphate translocase in brain tumor progression.
AB  - BACKGROUND: Chlorogenic acid (CHL), the most potent functional inhibitor of the
      microsomal glucose-6-phosphate translocase (G6PT), is thought to possess cancer
      chemopreventive properties. It is not known, however, whether any G6PT functions
      are involved in tumorigenesis. We investigated the effects of CHL and the
      potential role of G6PT in regulating the invasive phenotype of brain tumor
      derived glioma cells. RESULTS: RT-PCR was used to show that, among the adult and
      pediatric brain tumor-derived cells tested, U-87 glioma cells expressed the
      highest levels of G6PT mRNA. U-87 cells lacked the microsomal catalytic subunit
      glucose-6-phosphatase (G6Pase)-alpha but expressed G6Pase-beta which, when
      coupled to G6PT, allows G6P hydrolysis into glucose to occur in non-glyconeogenic
      tissues such as brain. CHL inhibited U-87 cell migration and matrix
      metalloproteinase (MMP)-2 secretion, two prerequisites for tumor cell invasion.
      Moreover, CHL also inhibited cell migration induced by sphingosine-1-phosphate
      (S1P), a potent mitogen for glioblastoma multiform cells, as well as the rapid,
      S1P-induced extracellular signal-regulated protein kinase phosphorylation
      potentially mediated through intracellular calcium mobilization, suggesting that
      G6PT may also perform crucial functions in regulating intracellular signalling.
      Overexpression of the recombinant G6PT protein induced U-87 glioma cell migration
      that was, in turn, antagonized by CHL. MMP-2 secretion was also inhibited by the
      adenosine triphosphate (ATP)-depleting agents 2-deoxyglucose and 5-thioglucose, a
      mechanism that may inhibit ATP-mediated calcium sequestration by G6PT.
      CONCLUSION: We illustrate a new G6PT function in glioma cells that could regulate
      the intracellular signalling and invasive phenotype of brain tumor cells, and
      that can be targeted by the anticancer properties of CHL.

PMID- 16566827
TI  - Lipopolysaccharide regulated protein expression is only partly impaired in
      monocytes from patients with type I diabetes.
AB  - BACKGROUND: Monocytes play an important role in innate immunity and
      atherosclerosis. A disturbed secretion of cytokines in lipopolysaccharide (LPS)
      activated monocytes from type 1 diabetes (T1D) patients has been described and
      may contribute to the impaired inflammatory response in these individuals. In the
      present study the influence of LPS on five different proteins with a function in
      immunity and atherosclerosis was analyzed in monocytes from controls and T1D
      patients. METHODS: Monocytes were isolated from controls and T1D patients and the
      LPS-stimulated increase of IL-6, CXCL8, monocyte chemotactic protein 1 (CCL2, MCP
      1) and superoxide dismutase (SOD 2), as well as the LPS-mediated decrease of
      apolipoprotein E (Apo E) in primary human monocytes from controls and T1D
      patients was determined. RESULTS: CCL2 and IL-6 secretion in response to LPS was
      found significantly reduced in monocytes from T1D patients when compared to
      controls whereas basal CCL2 release was similar in control and T1D cells. In
      contrast, CXCL8 and apolipoprotein E secretion and SOD 2 expression upon LPS
      stimulation is similar from T1D and control monocytes. CONCLUSION: These data
      indicate that LPS-mediated protein expression is only partly disturbed in
      monocytes from T1D patients. Reduced secretion of IL-6 and CCL2 in activated
      monocytes of these patients may contribute to an impaired inflammatory response
      and vascular disease.

PMID- 16566829
TI  - EAAC1 is expressed in rat and human prostate epithelial cells; functions as a
      high-affinity L-aspartate transporter; and is regulated by prolactin and
      testosterone.
AB  - BACKGROUND: Prostate epithelial cells accumulate a high level of aspartate that
      is utilized as a substrate for their unique function of production and secretion
      of enormously high levels of citrate. In most mammalian cells aspartate is
      synthesized; and, therefore is a non-essential amino acid. In contrast, in
      citrate-producing prostate cells, aspartate is an essential amino acid that must
      be derived from circulation. The prostate intracellular/extracellular conditions
      present a 40:1 concentration gradient. Therefore, these cells must possess a
      plasma membrane-associated aspartate uptake transport process to achieve their
      functional activity. In earlier kinetic studies we identified the existence of a
      unique Na+-dependent high-affinity L-aspartate transport process in rat prostate
      secretory epithelial cells. The present report is concerned with the
      identification of this putative L-aspartate transporter in rat and human prostate
      cells. RESULTS: The studies show for the first time that EAAC1 is expressed in
      normal rat prostate epithelial cells, in normal and hyperplastic human prostate
      glands, and in human malignant prostate cell lines. EAAC1 expression and high
      affinity L-aspartate transport are correspondingly down-regulated by EAAC1 siRNA
      knock down. Exposure of prostate cells to physiological levels of prolactin or
      testosterone results in an up-regulation of EAAC1 expression and a corresponding
      increase in the high-affinity transport of L-aspartate into the cells.
      CONCLUSION: This study shows that EAAC1 functions as the high-affinity L
      aspartate transporter that is responsible for the uptake and accumulation of
      aspartate in prostate cells. In other cells (predominantly excitable tissue
      cells), EAAC1 has been reported to function as a glutamate transporter rather
      than as an aspartate transporter. The regulation of EAAC1 expression and L
      aspartate transport by testosterone and prolactin is consistent with their
      regulation of citrate production in prostate cells. The identification of EAAC1
      as the high-affinity L-aspartate transporter now permits studies to elucidate the
      mechanism of hormonal regulation of EAAC1 gene expression, and to investigate the
      mechanism by which the cellular environment effects the functioning of EAAC1 as
      an aspartate transporter or as a glutamate transporter.

PMID- 16566830
TI  - Spatial and temporal structure of typhoid outbreaks in Washington, D.C., 1906
      1909: evaluating local clustering with the Gi* statistic.
AB  - BACKGROUND: To better understand the distribution of typhoid outbreaks in
      Washington, D.C., the U.S. Public Health Service (PHS) conducted four
      investigations of typhoid fever. These studies included maps of cases reported
      between 1 May - 31 October 1906 - 1909. These data were entered into a GIS
      database and analyzed using Ripley's K-function followed by the Gi* statistic in
      yearly intervals to evaluate spatial clustering, the scale of clustering, and the
      temporal stability of these clusters. RESULTS: The Ripley's K-function indicated
      no global spatial autocorrelation. The Gi* statistic indicated clustering of
      typhoid at multiple scales across the four year time period, refuting the
      conclusions drawn in all four PHS reports concerning the distribution of cases.
      While the PHS reports suggested an even distribution of the disease, this study
      quantified both areas of localized disease clustering, as well as mobile larger
      regions of clustering. Thus, indicating both highly localized and periodic
      generalized sources of infection within the city. CONCLUSION: The methodology
      applied in this study was useful for evaluating the spatial distribution and
      annual-level temporal patterns of typhoid outbreaks in Washington, D.C. from 1906
      to 1909. While advanced spatial analyses of historical data sets must be
      interpreted with caution, this study does suggest that there is utility in these
      types of analyses and that they provide new insights into the urban patterns of
      typhoid outbreaks during the early part of the twentieth century.

PMID- 16566828
TI  - The role of endothelin-1 in hyperoxia-induced lung injury in mice.
AB  - BACKGROUND: As prolonged hyperoxia induces extensive lung tissue damage, we set
      out to investigate the involvement of endothelin-1 (ET-1) receptors in these
      adverse changes. METHODS: Experiments were performed on four groups of mice:
      control animals kept in room air and a group of mice exposed to hyperoxia for 60
      h were not subjected to ET-1 receptor blockade, whereas the dual ETA/ETB-receptor
      blocker tezosantan (TEZ) was administered via an intraperitoneal pump (10
      mg/kg/day for 6 days) to other groups of normal and hyperoxic mice. The
      respiratory system impedance (Zrs) was measured by means of forced oscillations
      in the anesthetized, paralyzed and mechanically ventilated mice before and after
      the iv injection of ET-1 (2 microg). Changes in the airway resistance (Raw) and
      in the tissue damping (G) and elastance (H) of a constant-phase tissue
      compartment were identified from Zrs by model fitting. RESULTS: The plasma ET-1
      level increased in the mice exposed to hyperoxia (3.3 +/- 1.6 pg/ml) relative to
      those exposed to room air (1.6 +/- 0.3 pg/ml, p < 0.05). TEZ administration
      prevented the hyperoxia-induced increases in G (13.1 +/- 1.7 vs. 9.6 +/- 0.3
      cmH2O/l, p < 0.05) and H (59 +/- 9 vs. 41 +/- 5 cmH2O/l, p < 0.05) and inhibited
      the lung responses to ET-1. Hyperoxia decreased the reactivity of the airways to
      ET-1, whereas it elevated the reactivity of the tissues. CONCLUSION: These
      findings substantiate the involvement of the ET-1 receptors in the
      physiopathogenesis of hyperoxia-induced lung damage. Dual ET-1 receptor
      antagonism may well be of value in the prevention of hyperoxia-induced
      parenchymal damage.

PMID- 16566831
TI  - Guinea pigs: a suitable animal model to study lipoprotein metabolism,
      atherosclerosis and inflammation.
AB  - Numerous animal models have been used to study diet effects on cholesterol and
      lipoprotein metabolism. However, most of those models differ from humans in the
      plasma distribution of cholesterol and in the processing of lipoproteins in the
      plasma compartment. Although transgenic or knock-out mice have been used to study
      a specific pathway involved in cholesterol metabolism, these data are of limited
      use because other metabolic pathways and responses to interventions may differ
      from the human condition. Carbohydrate restricted diets have been shown to reduce
      plasma triglycerides, increase HDL cholesterol and promote the formation of
      larger, less atherogenic LDL. However, the mechanisms behind these responses and
      the relation to atherosclerotic events in the aorta have not been explored in
      detail due to the lack of an appropriate animal model. Guinea pigs carry the
      majority of the cholesterol in LDL and possess cholesterol ester transfer protein
      and lipoprotein lipase activities, which results in reverse cholesterol transport
      and delipidation cascades equivalent to the human situation. Further,
      carbohydrate restriction has been shown to alter the distribution of LDL
      subfractions, to decrease cholesterol accumulation in aortas and to decrease
      aortic cytokine expression. It is the purpose of this review to discuss the use
      of guinea pigs as useful models to evaluate diet effects on lipoprotein
      metabolism, atherosclerosis and inflammation with an emphasis on carbohydrate
      restricted diets.

PMID- 16566832
TI  - Can HRCT be used as a marker of airway remodelling in children with difficult
      asthma?
AB  - BACKGROUND: Whole airway wall thickening on high resolution computed tomography
      (HRCT) is reported to parallel thickening of the bronchial epithelial reticular
      basement membrane (RBM) in adult asthmatics. A similar relationship in children
      with difficult asthma (DA), in whom RBM thickening is a known feature, may allow
      the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this
      relationship in children with DA. METHODS: 27 children (median age 10.5 [range
      4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower
      lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall
      thickening (BWT) of the right lower lobe using semi-quantitative and quantitative
      scoring techniques. The semi-quantitative score (grade 0-4) was an overall
      assessment of BWT of all clearly identifiable airways in HRCT scans. The
      quantitative score (BWT %; defined as [airway outer diameter - airway lumen
      diameter]/airway outer diameter x100) was the average score of all airways
      visible and calculated using electronic endpoint callipers. RBM thickness in
      endobronchial biopsies was measured using image analysis. 23/27 subjects
      performed spirometry and the relationships between RBM thickness and BWT with
      airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial
      biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the
      right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2
      65.6)%. There was no relationship between RBM thickness and BWT in the right
      lower lobe using either scoring technique. No relationship was found between FEV1
      and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM
      thickness and BWT on HRCT has been found in adults with asthma, this relationship
      does not appear to hold true in children with DA.

PMID- 16566833
TI  - Differences in avoidable mortality between migrants and the native Dutch in The
      Netherlands.
AB  - BACKGROUND: The quality of the healthcare system and its role in influencing
      mortality of migrant groups can be explored by examining ethnic variations in
      'avoidable' mortality. This study investigates the association between the level
      of mortality from 'avoidable' causes and ethnic origin in the Netherlands and
      identifies social factors that contribute to this association. METHODS: Data were
      obtained from cause of death and population registries in the period 1995-2000.
      We compared mortality rates for selected 'avoidable' conditions for Turkish,
      Moroccan, Surinamese and Antillean/Aruban groups to native Dutch. RESULTS: We
      found slightly elevated risk in total 'avoidable' mortality for migrant
      populations (RR = 1.13). Higher risks of death among migrants were observed from
      almost all infectious diseases (most RR > 3.00) and several chronic conditions
      including asthma, diabetes and cerebro-vascular disorders (most RR > 1.70).
      Migrant women experienced a higher risk of death from maternity-related
      conditions (RR = 3.37). Surinamese and Antillean/Aruban population had a higher
      mortality risk (RR = 1.65 and 1.31 respectively), while Turkish and Moroccans
      experienced a lower risk of death (RR = 0.93 and 0.77 respectively) from all
      'avoidable' conditions compared to native Dutch. Control for demographic and
      socioeconomic factors explained a substantial part of ethnic differences in
      'avoidable' mortality. CONCLUSION: Compared to the native Dutch population, total
      'avoidable' mortality was slightly elevated for all migrants combined. Mortality
      risks varied greatly by cause of death and ethnic origin. The substantial
      differences in mortality for a few 'avoidable' conditions suggest opportunities
      for quality improvement within specific areas of the healthcare system targeted
      to disadvantaged groups.

PMID- 16566835
TI  - Breast metastasis of ilial carcinoid tumor: case report and literature review.
AB  - BACKGROUND: Metastatic breast carcinoids are rare neoplasms. They can be mistaken
      for primary breast carcinoma both clinically and radiologically, even with known
      history of carcinoid tumor elsewhere in the body. CASE PRESENTATION: We report a
      case of unilateral breast metastasis from carcinoid tumor of the small intestine
      in a 52-year-old woman who was successfully treated by lumpectomy and radiation
      therapy. An extensive review of the literature reveals only a few cases of
      metastatic carcinoid to the breast from small intestinal primaries. CONCLUSION:
      Clinical suspicion for metastasis should be high in a patient with breast mass
      and history of known carcinoid elsewhere in the body. Lumpectomy alone may be
      effective in these patients. Mastectomy and especially axillary dissection could
      be avoided. Their histological appearance may mimic ductal adenocarcinoma of the
      breast. However, the distinction is important due to differences in management
      and prognosis.

PMID- 16566834
TI  - Cerebrospinal fluid HIV-1 RNA, intrathecal immunoactivation, and drug
      concentrations after treatment with a combination of saquinavir, nelfinavir, and
      two nucleoside analogues: the M61022 study.
AB  - BACKGROUND: The way various antiretroviral drugs and drug combinations affect HIV
      1 infection in the central nervous system is still largely unknown. The aim of
      this study was to determine the cerebrospinal fluid (CSF) steady-state
      concentrations of saquinavir and nelfinavir in relation to plasma concentrations,
      and to study their effect in combination with two nucleoside reverse
      transcriptase inhibitors (NRTIs) on CSF viral loads, intrathecal
      immunoactivation, and blood-brain barrier integrity. METHODS: Paired CSF and
      plasma samples from 8 antiretroviral-naive HIV-1 infected patients starting
      combination therapy with saquinavir, nelfinavir, and two nucleoside analogues
      were collected prior to treatment, and again after approximately 12 and 48 weeks
      of antiretroviral therapy. Additional plasma samples were taken at weeks 2, 4, 8,
      24, and 36. The concentrations of protease inhibitors were analysed, as were
      levels of HIV-1 RNA, CD4+ T-cell count, beta2-microglobulin, neopterin, albumin
      ratio, IgG index, and monocytic cell count. RESULTS: None of the patients in the
      study presented with HIV-1 RNA < 50 copies/mL in CSF or plasma prior to
      treatment, compared to 5/7 at the end of the study. Signs of cell-mediated
      intrathecal immunoactivation, measured by neopterin and beta2-microglobulin,
      decreased significantly in both CSF and serum, although only 1/7 reached normal
      CSF neopterin levels after 48 weeks of treatment. There was no significant
      reduction of albumin ratio, IgG index or CSF monocytic cell count. Saquinavir
      median (range) concentrations were < 2.5 (< 2.5-96.0) nM unbound in plasma, and <
      2.5 (< 2.5-9.0) nM total in CSF. Nelfinavir median (range) concentrations were
      10.0 (< 2.0-31.0) nM unbound in plasma, and < 2.0 (< 2.0-23.0) nM total in CSF.
      Saquinavir and nelfinavir were detectable in 7/15 and 9/15 CSF samples,
      respectively. CONCLUSION: Saquinavir and nelfinavir, in combination with two
      NRTIs, decrease the CSF viral load and, to a lesser extent, intrathecal
      immunoactivation. We found reasonably high CSF concentrations of nelfinavir, but
      suboptimal concentrations of saquinavir.

PMID- 16566836
TI  - Detection of non-coding RNAs on the basis of predicted secondary structure
      formation free energy change.
AB  - BACKGROUND: Non-coding RNAs (ncRNAs) have a multitude of roles in the cell, many
      of which remain to be discovered. However, it is difficult to detect novel ncRNAs
      in biochemical screens. To advance biological knowledge, computational methods
      that can accurately detect ncRNAs in sequenced genomes are therefore desirable.
      The increasing number of genomic sequences provides a rich dataset for
      computational comparative sequence analysis and detection of novel ncRNAs.
      RESULTS: Here, Dynalign, a program for predicting secondary structures common to
      two RNA sequences on the basis of minimizing folding free energy change, is
      utilized as a computational ncRNA detection tool. The Dynalign-computed optimal
      total free energy change, which scores the structural alignment and the free
      energy change of folding into a common structure for two RNA sequences, is shown
      to be an effective measure for distinguishing ncRNA from randomized sequences. To
      make the classification as a ncRNA, the total free energy change of an input
      sequence pair can either be compared with the total free energy changes of a set
      of control sequence pairs, or be used in combination with sequence length and
      nucleotide frequencies as input to a classification support vector machine. The
      latter method is much faster, but slightly less sensitive at a given specificity.
      Additionally, the classification support vector machine method is shown to be
      sensitive and specific on genomic ncRNA screens of two different Escherichia coli
      and Salmonella typhi genome alignments, in which many ncRNAs are known. The
      Dynalign computational experiments are also compared with two other ncRNA
      detection programs, RNAz and QRNA. CONCLUSION: The Dynalign-based support vector
      machine method is more sensitive for known ncRNAs in the test genomic screens
      than RNAz and QRNA. Additionally, both Dynalign-based methods are more sensitive
      than RNAz and QRNA at low sequence pair identities. Dynalign can be used as a
      comparable or more accurate tool than RNAz or QRNA in genomic screens, especially
      for low-identity regions. Dynalign provides a method for discovering ncRNAs in
      sequenced genomes that other methods may not identify. Significant improvements
      in Dynalign runtime have also been achieved.

PMID- 16566837
TI  - Hormonal regulation of alveolarization: structure-function correlation.
AB  - BACKGROUND: Dexamethasone (Dex) limits and all-trans-retinoic acid (RA) promotes
      alveolarization. While structural changes resulting from such hormonal exposures
      are known, their functional consequences are unclear. METHODS: Neonatal rats were
      treated with Dex and/or RA during the first two weeks of life or were given RA
      after previous exposure to Dex. Morphology was assessed by light microscopy and
      radial alveolar counts. Function was evaluated by plethysmography at d13,
      pressure volume curves at d30, and exercise swim testing and arterial blood gases
      at both d15 and d30. RESULTS: Dex-treated animals had simplified lung
      architecture without secondary septation. Animals given RA alone had smaller,
      more numerous alveoli. Concomitant treatment with Dex + RA prevented the Dex
      induced changes in septation. While the results of exposure to Dex + RA were
      sustained, the effects of RA alone were reversed two weeks after treatment was
      stopped. At d13, Dex-treated animals had increased lung volume, respiratory rate,
      tidal volume, and minute ventilation. On d15, both RA- and Dex-treated animals
      had hypercarbia and low arterial pH. By d30, the RA-treated animals resolved this
      respiratory acidosis, but Dex-treated animals continued to demonstrate blood gas
      and lung volume abnormalities. Concomitant RA treatment improved respiratory
      acidosis, but failed to normalize Dex-induced changes in pulmonary function and
      lung volumes. No differences in exercise tolerance were noted at either d15 or
      d30. RA treatment after the period of alveolarization also corrected the effects
      of earlier Dex exposure, but the structural changes due to RA alone were again
      lost two weeks after treatment. CONCLUSION: We conclude that both RA- and
      corticosteroid-treatments are associated with respiratory acidosis at d15. While
      RA alone-induced changes in structure andrespiratory function are reversed, Dex
      treated animals continue to demonstrate increased respiratory rate, minute
      ventilation, tidal and total lung volumes at d30. Concomitant treatment with Dex
      + RA prevents decreased septation induced by Dex alone and results in correction
      of hypercarbia. However, these animals continue to have abnormal pulmonary
      function and lung volumes. Increased septation as a result of RA treatment alone
      is reversed upon discontinuation of treatment. These data suggest that Dex + RA
      treatment results in improved gas exchange likely secondary to normalized
      septation.

PMID- 16566838
TI  - Anthropometric measures in relation to basal cell carcinoma: a longitudinal
      study.
AB  - BACKGROUND: The relationship between anthropometric indices and risk of basal
      cell carcinoma (BCC) is largely unknown. We aimed to examine the association
      between anthropometric measures and development of BCC and to demonstrate whether
      adherence to World Health Organisation guidelines for body mass index, waist
      circumference, and waist/hip ratio was associated with risk of BCC, independent
      of sun exposure. METHODS: Study participants were participants in a community
      based skin cancer prevention trial in Nambour, a town in southeast Queensland
      (latitude 26 degrees S). In 1992, height, weight, and waist and hip
      circumferences were measured for all 1621 participants and weight was remeasured
      at the end of the trial in 1996. Prevalence proportion ratios were calculated
      using a log-binomial model to estimate the risk of BCC prior to or prevalent in
      1992, while Poisson regression with robust error variances was used to estimate
      the relative risk of BCC during the follow-up period. RESULTS: At baseline, 94
      participants had a current BCC, and 202 had a history of BCC. During the 5-year
      follow-up period, 179 participants developed one or more new BCCs. We found no
      significant association between any of the anthropometric measures or indices and
      risk of BCC after controlling for potential confounding factors including sun
      exposure. There was a suggestion that short-term weight gain may increase the
      risk of developing BCC for women only. CONCLUSION: Adherence to World Health
      Organisation guidelines for body mass index, waist circumference and waist/hip
      ratio is not significantly associated with occurrence of basal cell carcinomas of
      the skin.

PMID- 16566839
TI  - Structural proteomics of minimal organisms: conservation of protein fold usage
      and evolutionary implications.
AB  - BACKGROUND: Determining the complete repertoire of protein structures for all
      soluble, globular proteins in a single organism has been one of the major goals
      of several structural genomics projects in recent years. RESULTS: We report that
      this goal has nearly been reached for several "minimal organisms"--parasites or
      symbionts with reduced genomes--for which over 95% of the soluble, globular
      proteins may now be assigned folds, overall 3-D backbone structures. We analyze
      the structures of these proteins as they relate to cellular functions, and
      compare conservation of fold usage between functional categories. We also compare
      patterns in the conservation of folds among minimal organisms and those observed
      between minimal organisms and other bacteria. CONCLUSION: We find that proteins
      performing essential cellular functions closely related to transcription and
      translation exhibit a higher degree of conservation in fold usage than proteins
      in other functional categories. Folds related to transcription and translation
      functional categories were also overrepresented in minimal organisms compared to
      other bacteria.

PMID- 16566841
TI  - A population-based model for priority setting across the care continuum and
      across modalities.
AB  - BACKGROUND: The Health-sector Wide (HsW) priority setting model is designed to
      shift the focus of priority setting away from 'program budgets'--that are
      typically defined by modality or disease-stage--and towards well-defined target
      populations with a particular disease/health problem. METHODS: The key features
      of the HsW model are i) a disease/health problem framework, ii) a sequential
      approach to covering the entire health sector, iii) comprehensiveness of scope in
      identifying intervention options and iv) the use of objective evidence. The HsW
      model redefines the unit of analysis over which priorities are set to include all
      mutually exclusive and complementary interventions for the prevention and
      treatment of each disease/health problem under consideration. The HsW model is
      therefore incompatible with the fragmented approach to priority setting across
      multiple program budgets that currently characterises allocation in many health
      systems. The HsW model employs standard cost-utility analyses and decision-rules
      with the aim of maximising QALYs contingent upon the global budget constraint for
      the set of diseases/health problems under consideration. It is recognised that
      the objective function may include non-health arguments that would imply a
      departure from simple QALY maximisation and that political constraints frequently
      limit degrees of freedom. In addressing these broader considerations, the HsW
      model can be modified to maximise value-weighted QALYs contingent upon the global
      budget constraint and any political constraints bearing upon allocation
      decisions. RESULTS: The HsW model has been applied in several contexts, recently
      to osteoarthritis, that has demonstrated both its practical application and its
      capacity to derive clear evidenced-based policy recommendations. CONCLUSION:
      Comparisons with other approaches to priority setting, such as Programme
      Budgeting and Marginal Analysis (PBMA) and modality-based cost-effectiveness
      comparisons, as typified by Australia's Pharmaceutical Benefits Advisory
      Committee process for the listing of pharmaceuticals for government funding,
      demonstrate the value added by the HsW model notably in its greater likelihood of
      contributing to allocative efficiency.

PMID- 16566840
TI  - Bacteria and cancer: cause, coincidence or cure? A review.
AB  - Research has found that certain bacteria are associated with human cancers. Their
      role, however, is still unclear. Convincing evidence links some species to
      carcinogenesis while others appear promising in the diagnosis, prevention or
      treatment of cancers. The complex relationship between bacteria and humans is
      demonstrated by Helicobacter pylori and Salmonella typhi infections. Research has
      shown that H. pylori can cause gastric cancer or MALT lymphoma in some
      individuals. In contrast, exposure to H. pylori appears to reduce the risk of
      esophageal cancer in others. Salmonella typhi infection has been associated with
      the development of gallbladder cancer; however S. typhi is a promising carrier of
      therapeutic agents for melanoma, colon and bladder cancers. Thus bacterial
      species and their roles in particular cancers appear to differ among different
      individuals. Many species, however, share an important characteristic: highly
      site-specific colonization. This critical factor may lead to the development of
      non-invasive diagnostic tests, innovative treatments and cancer vaccines.

PMID- 16566842
TI  - Youth at risk of physical inactivity may benefit more from activity-related
      support than youth not at risk.
AB  - BACKGROUND: This study examines whether associations between activity-related
      support and adolescents' physical activity differ for adolescents at high versus
      low risk of physical inactivity. METHODS: Participants included 202 middle-school
      aged girls (N = 92) and boys (N = 110). Physical activity was assessed using
      three self-report questionnaires. Activity-related support from mothers, fathers,
      siblings, and peers was assessed using the Activity Support Scale. Perceived
      sport competence was assessed using the Physical Activity Self Description
      Questionnaire. Participants' height and weight were measured and used to
      calculate their age- and sex-adjusted Body Mass Index percentile. Participants
      were classified as being at high risk for physical inactivity if they fulfilled
      two of the following three criteria: (1) overweight; (2) female; or (3) having
      low perceived sport competence. RESULTS: Activity-related support from all
      sources was associated with higher levels of physical activity among adolescents.
      A stronger association between activity support and physical activity was found
      for adolescents at high risk for physical inactivity in comparison to adolescents
      at low risk. CONCLUSIONS: Findings from this study suggest that the activity
      related support from family and friends may be an effective tool in promoting
      physical activity among youth at risk of physical inactivity.

PMID- 16566844
TI  - Chiral trimethylsilylated C2-symmetrical diamines as phosphorous derivatizing
      agents for the determination of the enantiomeric excess of chiral alcohols by 1H
      NMR.
AB  - The use of organophosphorus derivatising agents, prepared from C2 symmetric
      trimethylsilylated diamines, for the 1H NMR and 31P NMR determination of the
      enantiomeric composition of chiral alcohols is described.

PMID- 16566845
TI  - Aldehyde dehydrogenase is essential for both adult and larval ethanol resistance
      in Drosophila melanogaster.
AB  - The enzyme aldehyde dehydrogenase (ALDH) is essential for ethanol metabolism in
      mammals, converting the highly toxic intermediate acetaldehyde to acetate. The
      role of ALDH in Drosophila has been debated, with some authors arguing that, at
      least in larvae, acetaldehyde detoxification is carried out mainly by alcohol
      dehydrogenase (ADH), the enzyme responsible for converting ethanol to
      acetaldehyde. Here, we report the creation and characterization of four null
      mutants of Aldh, the putative structural locus for ALDH. Aldh null larvae and
      adults are poisoned by ethanol concentrations easily tolerated by wild-types;
      their ethanol sensitivity is in fact comparable to that of Adh nulls. The results
      refute the view that ALDH plays only a minor role in ethanol detoxification in
      larvae, and suggest that Aldh and Adh may be equally important players in the
      evolution of ethanol resistance in fruit-breeding Drosophila.

PMID- 16566846
TI  - Fertility intentions: are the undecided more like those who want more or want no
      more children?
AB  - In fertility surveys often women (and sometimes men) are asked their fertility
      desires, i.e. whether they want a/nother birth or not. Some respond that they are
      undecided. This study examines whether these persons are more like those who say
      they want more births or like those who say they want no more births. Data on
      married men and women in 29 Demographic and Health Surveys with sample sizes
      ranging from 300 to 3000 are used. A logistic regression equation is estimated
      within each country for those with known desires and then used to classify each
      person who was undecided. In all sub-Saharan African countries (n=20) and for
      both sexes, 50% or more of the undecided persons are classified as wanting more
      children (with one exception of wives in Kenya). By contrast in all five Latin
      American countries for both sexes less than 50% of the undecided were classified
      in the 'want more' group (with an exception of husbands in the Dominican
      Republic). Generally, the undecided tend to be classified the same as the
      majority among those in the survey with stated desires.

PMID- 16566843
TI  - Comparison of P2X and TRPV1 receptors in ganglia or primary culture of trigeminal
      neurons and their modulation by NGF or serotonin.
AB  - BACKGROUND: Cultured sensory neurons are a common experimental model to elucidate
      the molecular mechanisms of pain transduction typically involving activation of
      ATP-sensitive P2X or capsaicin-sensitive TRPV1 receptors. This applies also to
      trigeminal ganglion neurons that convey pain inputs from head tissues. Little is,
      however, known about the plasticity of these receptors on trigeminal neurons in
      culture, grown without adding the neurotrophin NGF which per se is a powerful
      algogen. The characteristics of such receptors after short-term culture were
      compared with those of ganglia. Furthermore, their modulation by chronically
      applied serotonin or NGF was investigated. RESULTS: Rat or mouse neurons in
      culture mainly belonged to small and medium diameter neurons as observed in
      sections of trigeminal ganglia. Real time RT-PCR, Western blot analysis and
      immunocytochemistry showed upregulation of P2X(3) and TRPV1 receptors after 1-4
      days in culture (together with their more frequent co-localization), while P2X(2)
      ones were unchanged. TRPV1 immunoreactivity was, however, lower in mouse ganglia
      and cultures. Intracellular Ca(2+) imaging and whole-cell patch clamping showed
      functional P2X and TRPV1 receptors. Neurons exhibited a range of responses to the
      P2X agonist alpha, beta-methylene-adenosine-5'-triphosphate indicating the
      presence of homomeric P2X(3) receptors (selectively antagonized by A-317491) and
      heteromeric P2X(2/3) receptors. The latter were observed in 16 % mouse neurons
      only. Despite upregulation of receptors in culture, neurons retained the
      potential for further enhancement of P2X(3) receptors by 24 h NGF treatment. At
      this time point TRPV1 receptors had lost the facilitation observed after acute
      NGF application. Conversely, chronically-applied serotonin selectively
      upregulated TRPV1 receptors rather than P2X(3) receptors. CONCLUSION: Comparing
      ganglia and cultures offered the advantage of understanding early adaptive
      changes of nociception-transducing receptors of trigeminal neurons. Culturing did
      not prevent differential receptor upregulation by algogenic substances like NGF
      or serotonin, indicating that chronic application led to distinct plastic changes
      in the molecular mechanisms mediating pain on trigeminal nociceptors.

PMID- 16566847
TI  - Determinants of chronic malnutrition among preschool children in Bangladesh.
AB  - This study investigated the impact of some socioeconomic, demographic and health
      and community factors on chronic malnutrition or stunting in Bangladeshi children
      aged less than 5 years. The analysis revealed that the overall prevalence of
      stunting was 44%, of which 18% of children were severely stunted, and the
      demographic characteristics appeared to be the most significant factors for
      chronic malnutrition. Multinomial logistic regression analysis showed that
      parents' education, household economic status, media exposure, number of under-5
      children, place of delivery, child's age, birth order, months of breast-feeding,
      birth size, mother's BMI, mother's height, age of household head, measles
      vaccine, supplementation of diet with liquids and regional differentials were
      significantly associated with severe as well as moderate stunting.

PMID- 16566848
TI  - Coerced first sexual intercourse and selected reproductive health outcomes among
      young women in KwaZulu-Natal, South Africa.
AB  - Coercion may play an important role in compelling young women to engage in sexual
      intercourse at an early age. With a decline in age at first intercourse and
      increased reporting of coercive first sex, concerns of adverse reproductive
      health outcomes such as unintended pregnancy and sexually transmitted infections
      (STIs), including HIV, have become important issues, particularly in the context
      of a high HIV prevalence. This paper uses data collected in 2001 from the second
      round of a longitudinal study of 1130 sexually experienced young women in KwaZulu
      Natal to investigate the relationship between coerced first intercourse and
      selected reproductive health outcomes and behaviours. Nearly 46% of all sexually
      experienced young women had reported that their first sexual encounter had been
      coerced. Young women who reported being coerced at first sex were significantly
      more likely to be Black and living in an urban area. Those who had been coerced
      at first sex were also more likely to report having had an STI and having
      experienced unintended pregnancy, than those who had not been coerced at first
      sex. Coercion at first sex is an important social and public health problem that
      has a serious impact on the reproductive health and behaviours of young women.
      Interventions should directly address the issue of sexual coercion by ensuring
      young women are aware of their reproductive rights.

PMID- 16566850
TI  - Clinical and neuropsychological characteristics of child and adolescent bipolar
      disorder.
AB  - BACKGROUND: The diagnosis of bipolar disorder in pre-pubertal populations remains
      difficult and often controversial. Consequently, the clinical and
      neuropsychological characteristics of mania in the child and adolescent years
      remain poorly defined. This review provides a clinical account of childhood and
      adolescent bipolar disorder and compares the neuropsychology and neuroanatomy of
      young BPD patients compared with adult BPD and childhood syndromes of attention
      deficit hyperactivity disorder (ADHD) and conduct disorder (CD). METHOD:
      Literature review based on Pubmed searches. RESULTS: Early- and adult-onset mania
      and BPD may share a common pattern of neurobiological characteristics despite
      developmental variations in the clinical presentation. In contrast, important
      distinctions are apparent between the child-onset syndromes of BPD, ADHD and CD,
      specifically at the neural level. CONCLUSIONS: Disorders of affect dysregulation
      in childhood deserve closer neuroscientific and phenotypic scrutiny than given
      hitherto.

PMID- 16566849
TI  - The influence of adversity and perceived social support on the outcome of major
      depressive disorder in subjects with different levels of depressive symptoms.
AB  - BACKGROUND: Adverse life events and social support may influence the outcome of
      major depressive disorder (MDD). We hypothesized that outcome would depend on the
      level of depressive symptoms present at the outset, with those in partial
      remission being particularly vulnerable. METHOD: In the Vantaa Depression Study
      (VDS), patients with DSM-IV MDD were interviewed at baseline, and at 6 and 18
      months. Life events were investigated with the Interview for Recent Life Events
      (IRLE) and social support with the Interview Measure of Social Relationships
      (IMSR) and the Perceived Social Support Scale - Revised (PSSS-R). The patients
      were divided into three subgroups at 6 months, those in full remission (n = 68),
      partial remission (n = 75) or major depressive episode (MDE) (n = 50). The
      influence of social support and negative life events during the next 12 months on
      the level of depressive symptoms, measured by the Hamilton Rating Scale for
      Depression (HAMD), was investigated at endpoint. RESULTS: The severity of life
      events and perceived social support influenced the outcome of depression overall,
      even after adjusting for baseline level of depression and neuroticism. In the
      full remission subgroup, both severity of life events and subjective social
      support significantly predicted outcome. However, in the partial remission group,
      only the severity of events, and in the MDE group, the level of social support
      were significant predictors. CONCLUSIONS: Adverse life events and/or poor
      perceived social support influence the medium-term outcome of all psychiatric
      patients with MDD. These factors appear to have the strongest predictive value in
      the subgroup of patients currently in full remission.

PMID- 16566851
TI  - Role of calcium influx through voltage-operated calcium channels and of calcium
      mobilization in the physiology of Schistosoma mansoni muscle contractions.
AB  - We tested the hypothesis that voltage-operated Ca2+ channels mediate an
      extracellular Ca2+ influx in muscle fibres from the human parasite Schistosoma
      mansoni and, along with Ca2+ mobilization from the sarcoplasmic reticulum,
      contribute to muscle contraction. Indeed, whole-cell voltage clamp revealed
      voltage-gated inward currents carried by divalent ions with a peak current
      elicited by steps to +20 mV (from a holding potential of -70 mV). Depolarization
      of the fibres by elevated extracellular K+ elicited contractions that were
      completely dependent on extracellular Ca2+ and inhibited by nicardipine (half
      inhibition at 4.1 microM). However these contractions were not very sensitive to
      other classical blockers of voltage-gated Ca2+ channels, indicating that the
      schistosome muscle channels have an atypical pharmacology when compared to their
      mammalian counterparts. Futhermore, the contraction induced by 5 mM caffeine was
      inhibited after depletion of the sarcoplasmic reticulum either with thapsigargin
      (10 microM) or ryanodine (10 microM). These data suggest that voltage-operated
      Ca2+ channels do contribute to S. mansoni contraction as does the mobilization of
      stored Ca2+, despite the small volume of sarcoplasmic reticulum in schistosome
      smooth muscles.

PMID- 16566852
TI  - Resource predictability and host specificity in fleas: the effect of host body
      mass.
AB  - Ecological specialization is hypothesized to result from the exploitation of
      predictable resource bases. For parasitic organisms, one prediction is that
      parasites of large-bodied host species, which tend to be long-lived, should
      specialize on these hosts, whereas parasites of small host species, which
      represent more ephemeral and less predictable resources, should become
      generalists. We tested this prediction by quantifying the association between the
      level of host specificity of fleas and the mean body mass of their mammalian
      hosts, using published data from 2 large, distinct geographical regions (South
      Africa and northern North America). In general, we found supporting evidence that
      flea host specificity, measured either as the number of host species exploited or
      their taxonomic distinctness, became more pronounced with increasing host body
      mass. There were, however, some discrepancies among the results depending on the
      different measures of host specificity, the geographical region studied, or
      whether we used the raw values or phylogenetically independent contrasts. These
      are discussed with respect to other forces acting on the evolution of host
      specificity in parasites, as well as in the context of the regions' contrasting
      evolutionary histories. Overall, though, our findings indicate that the
      exploitation of large-bodied, and therefore long-lived, host species has promoted
      specialization in fleas, most likely because these hosts represent predictable
      resources.

PMID- 16566854
TI  - Survival of thermophilic spore-forming bacteria in a 90+ year old milk powder
      from Ernest Shackelton's Cape Royds Hut in Antarctica.
AB  - Milk powder taken to Antarctica on Shackelton's British Antarctic Expedition in
      1907 was produced in New Zealand by a roller drying process in the first factory
      in the world dedicated to this process. Thermophilic bacilli are the dominant
      contaminants of modern spray-dried milk powders and the 1907 milk powder allows a
      comparison to be made of contaminating strains in roller-dried and spray-dried
      powders. Samples of milk powder obtained from Shackelton's Hut at Cape Royds had
      low levels of thermophilic contamination (< 500 cfu ml-1) but the two dominant
      strains (Bacillus licheniformis strain F and Bacillus subtilis) were typical of
      those found in spray-dried powders. Soil samples from the floor of the hut also
      contained these strains, whereas soils distant from the hut did not. Differences
      in the RAPD profiles of isolates from the milk powder and the soils suggest that
      contamination of the milk from the soil was unlikely. It is significant that the
      most commonly encountered contaminant strain in modern spray-dried milk
      (Anoxybacillus flavithermus strain C) was not detected in the 1907 sample.

PMID- 16566853
TI  - Organophosphorus pesticides residues in Italian raw milk.
AB  - Organophosphorus pesticides (OPPs), widely used in agriculture, can cause toxic
      effects to humans and animals. The main purpose of the present work was to
      determine the contamination in raw milk by the main organophosphorus pesticides
      used in Italy and to evaluate the opportunity to start specific procedures of
      risk management along the milk production chain. The samples, collected in 4
      Italian dairy plants directly from the tank trucks during the delivering, were
      representative of 920 tonnes of raw milk. The isolation of the OPPs (acephate,
      chlorpyriphos, chlorpyriphos-methyl, diazinon, methamidophos, methidathion,
      phorate, pirimiphos-methyl) was performed by liquid partition followed by clean
      up with solid phase extraction. The analyses were carried out by dual column gas
      chromatography using two nitrogen-phosphorus detectors. Among the 135 samples
      analysed, 37 were positive in traces and 10 showed an OPP contamination ranging
      from 5 to 18 microg/kg. The higher results were recorded in the samples collected
      during the autumn-winter period. The main pollutants detected were acephate and
      chlorpyriphos. In every positive sample found, the OPP contamination was lower
      than the maximum residue level (MRL) fixed by the European Commission.

PMID- 16566855
TI  - Camel (Camelus dromedarius) immunoglobulin G, alpha-lactalbumin, serum albumin
      and lactoferrin in colostrum and milk during the early post partum period.
AB  - Colostrum and milk samples from twelve Tunisian camels were analysed for
      concentration of immunoglobulin G (IgG), alpha-lactalbumin (alpha-la), serum
      albumin (CSA) and lactoferrin throughout the first 14 milkings post partum (7
      days of lactation) using single radial immunodiffusion assay. Concentrations
      (mg/ml, means+/-SD) at first milking were IgG, 100.7+/-60.4; alpha-la, 2.2+/-0.7;
      CSA, 8.5+/-3.6 and lactoferrin, 1.2+/-0.3. Large variations were recorded for IgG
      and CSA concentrations (11.8-211.1 mg/ml and 2.9-13.8 mg/ml respectively)
      Concentrations of IgG and CSA dropped abruptly in the subsequent milkings while
      alpha-la concentration increased until milking 5 and then decreased slowly.
      Lactoferrin dropped only from milking 7. Mean IgG concentrations were 3.6 and 2.5
      mg/ml at milking 9 and 13 respectively. However, IgG concentration did not differ
      significantly, at the 1% level, from milkings 11 to 14. The contribution of CSA
      to the increase in whey proteins in early milks was greater than that described
      in the bovine and caprine species.

PMID- 16566856
TI  - Optimal settings of fingerprint-type analysing computer software for the analysis
      of enterohaemorrhagic Escherichia coli pulsed-field gel electrophoresis patterns.
AB  - Settings of fingerprint-type analysing computer software were optimized for
      analysis of enterohaemorrhagic Escherichia coli (EHEC) pulsed-field gel
      electrophoresis (PFGE) patterns. Under the lowest values of parameters, maximum
      value of similarities calculated using the Dice coefficient were obtained between
      PFGE patterns from one EHEC strain on the same gel when reference lanes for
      calibration of distortions during electrophoresis were set to every fourth lane.
      PFGE patterns of 15 EHEC strains on different gels were investigated. Similarity
      values calculated using the Pearson product-moment correlation coefficient
      (Pearson correlation) were significantly higher than those using the Dice
      coefficient with optimal values of parameters determined by the program (P <
      0.01). When PFGE patterns of 45 EHEC strains were analysed by the computer
      program, EHEC strains from one mass outbreak and three intra-family outbreaks
      were each clustered and the similarity values within the clusters were > 90%
      using Pearson correlation.

PMID- 16566857
TI  - T-cell subsets in the pathogenesis of human asthma.
AB  - Genetic predisposition and environmental instructions tune thresholds for
      activation of T cells, other inflammatory cells, and resident tissue cells in
      asthmatic inflammation. Selective migration of peripheral-blood T cells to the
      lungs, their survival and reactivation in the submucosa, and their effector
      functions represent sequential immunologic events. Activation-induced T-cell
      death and peripheral T-cell tolerance are critical events in disease
      pathogenesis. As a mechanism for peripheral Th2 response in atopic diseases,
      particularly, the high interferon (IFN)-gamma-producing Th1 compartment of
      activated effector T cells shows increased activation-induced cell death, skewing
      the immune response toward surviving Th2 cells in allergic asthma. After
      migration to asthmatic lung, these cells switch on effector cytokines and induce
      bronchial epithelial apoptosis with mainly IFN-gamma, tumor necrosis factor (TNF)
      alpha, and Fas-ligand. In addition, skewing of allergen-specific effector T cells
      to T-regulatory cells appears to be an essential event in the control of harmful
      immune response induced by allergens as a possible means for remedy.

PMID- 16566858
TI  - The role of the respiratory syncytial virus in airway syndromes in childhood.
AB  - The majority of infants admitted to hospital in infancy with lower respiratory
      tract infections (LRTIs) have been infected with the respiratory syncytial virus
      (RSV). Infants and young children experiencing RSV LRTIs experience increased
      respiratory morbidity in subsequent years, although the prevalence falls rapidly
      in early childhood. Recent data support the suggestion that in most subjects,
      this recurrent morbidity is not attributable to atopic asthma and that in most
      respects, the acute and long-term outcomes with RSV infections are similar in
      nature to those attributable to other viruses. The phenotype of the acute illness
      probably provides better prognostic information than the type of virus.

PMID- 16566859
TI  - Gene by environment interaction in asthma.
AB  - Asthma is a chronic inflammatory disease of the airways that is highly prevalent
      in the Western world. It is a genetically complex disease caused by multiple
      genetic and environmental factors, which may interact. Genetic research has
      recently incorporated environmental factors to investigate gene by environment
      interaction, and the first examples of gene by environment interaction in asthma
      have been reported. Linkage analyses indicate that one or more genes on
      chromosome 5q interact with environmental tobacco smoke in infancy in asthma
      development. Several candidate genes have been consistently shown to interact
      with the environment. These include the innate immunity genes CD14 and Toll-like
      receptor 4, and microbial exposures, as well as the detoxifying gene family
      glutathione-S-transferase and environmental tobacco smoke exposure and air
      pollutants. Gene by environment interaction is important in asthma pathogenesis,
      and future studies should take the interaction of both factors into account.

PMID- 16566860
TI  - The role of novel genes in modifying airway responses in asthma.
AB  - Major progress has been made during the past few years in developing a better
      understanding of the genetic basis of asthma, which has led to the identification
      of several chromosomal regions and loci showing linkage to and association with
      asthma and asthma-related phenotypes. Recent positional cloning approaches have
      also been informative in identifying several strong candidate genes for asthma.
      As another approach, association studies between candidate gene polymorphisms and
      asthma-related phenotypes have been conducted in many areas and replicated in
      different ethnic groups. These approaches need to be followed by validation
      processes to confirm their functional relevance in the pathophysiology of asthma.
      In this review, we describe several novel genes, including ADAM33, ADRB2, and
      eotaxin, that modify airway responsiveness in asthmatic patients.

PMID- 16566861
TI  - Cytokine and anti-cytokine therapy for asthma.
AB  - Cytokines play a critical role in the pathogenesis of asthma. Asthma resolution
      may depend on the correction of dysregulated cytokine expression, which is a
      characteristic feature of this chronic inflammatory disease. It is, therefore,
      not surprising that attempts have been made to either block cytokines present at
      elevated levels or to substitute cytokines that are insufficiently expressed in
      asthma. In this article, the results of these studies are discussed, and the
      obtained insights regarding asthma pathogenesis and new treatment options are
      summarized.

PMID- 16566863
TI  - Capsaicin treatment of idiopathic rhinitis: the new panacea?
AB  - The management of patients with perennial nonallergic or idiopathic rhinitis is
      difficult. Diagnosis and treatment are hampered by several factors. First, the
      diagnosis is made by exclusion of other nasal diseases. As a consequence,
      idiopathic rhinitis is not defined according to clear-cut criteria. A commonly
      accepted phenotype of idiopathic rhinitis does not exist. Second, the
      pathophysiology of idiopathic rhinitis is not yet fully elucidated. In contrast
      with allergic rhinitis, inflammation does not appear to play an important role in
      idiopathic rhinitis. Recent studies indicate a neural dysregulation of the nasal
      mucosa. Additionally, the available therapeutic arsenal comprising both
      pharmacotherapy and surgery is at best partially efficacious in these patients.
      The efficacy of repeated capsaicin application has been established in several
      randomized controlled trials. This treatment modality may be the first step to
      more specific and better treatment options for patients with idiopathic rhinitis
      that is unresponsive to standard treatment.

PMID- 16566862
TI  - Rhinitis in the elderly.
AB  - The effects of aging on the nose include structural, hormonal, mucosal,
      olfactory, and neural changes. As the US population ages and remains in overall
      better health, we will have more patients with rhinologic problems related to
      aging. In this manuscript, we review the available evidence on the structural and
      physiologic changes of the nose caused by aging, and we briefly describe
      management of common causes of rhinitis in the elderly.

PMID- 16566864
TI  - Animal models of food allergy: opportunities and barriers.
AB  - The potential for animal models to mimic the human disease process makes them an
      attractive tool for determining disease mechanisms, predicting disease triggers,
      and testing treatment regimens. With this in mind, animal models of food allergy
      have been receiving increasing attention as research tools to answer some of the
      difficult questions regarding food-allergy disease. Most of the food-allergy
      animal models developed to date have been designed to test reagents for
      immunotherapeutic treatment of allergic disease and to predict the potential
      human allergenicity of proteins. Current animal models under development are
      rodent, swine, and dog. The variables affecting development of such models
      include allergen concentration, allergen matrix or food source, allergen route of
      exposure, duration, animal age, adjuvant use, and dose range of allergens. Each
      model presents opportunities for and barriers to a fuller understanding of the
      allergic response. The conditions inherent to each model and the intended purpose
      of the study should therefore be considered prior to its use.

PMID- 16566866
TI  - Novel foods to treat food allergy and gastrointestinal infection.
AB  - The gastrointestinal tract communicates directly with the external environment.
      Necessary nutrients must be absorbed and commensal bacteria tolerated, and
      foreign proteins, antigens, and pathogens must be simultaneously excluded or
      destroyed. Immaturity or disruption of the mucosal immune defenses increases
      vulnerability to food allergy, intolerance, and infectious disease. Diseases
      resulting from ingested foreign proteins and organisms are increasing and cause
      morbidity and mortality worldwide. There is no specific treatment for food
      allergy other than avoidance. Vaccination for infectious disease is limited by
      the cost and logistics of distribution and administration, particularly in
      developing countries. Novel strategies are being explored to modulate the gut
      mucosal immune system by altering protein expression in food. Crops are being
      developed to remove deleterious allergens to prevent immunogenic exposure while
      preserving nutritional quality. Local food plants that express protein fragments
      of pathogens might provide an effective means to stimulate gut mucosal immunity
      while increasing vaccine accessibility.

PMID- 16566865
TI  - The diagnosis and management of egg allergy.
AB  - Egg allergy is a common food hypersensitivity in children. Atopic dermatitis
      represents the main clinical manifestation in infancy. On first exposure, many of
      these infants present with urticaria, angioedema, or anaphylaxis. The role of egg
      allergy in gastrointestinal conditions is less well understood. The "gold
      standard" for the diagnosis of egg allergy is the double-blind, placebo
      controlled food challenge. Diagnostic cut-off levels have been defined for food
      specific serum immunoglobulin E antibody level and skin prick test wheal diameter
      that predict an adverse challenge outcome. This has significantly reduced the
      need for formal food challenges. Atopy patch testing, in conjunction with
      immunoglobulin E-based tests, may further improve the accuracy of predicting a
      positive challenge. The treatment of egg allergy consists of dietary elimination,
      or a maternal elimination diet in breast-fed infants. Approximately two thirds of
      infants with egg allergy will become tolerant by 7 years of age.

PMID- 16566867
TI  - Avian influenza.
AB  - The current epidemic of H5N1 highly pathogenic avian influenza in Southeast Asia
      raises serious concerns that genetic reassortment will result in the next
      influenza pandemic. There have been 164 confirmed cases of human infection with
      avian influenza since 1996. In 2004 alone, there were 45 cases of human H5N1 in
      Vietnam and Thailand, with a mortality rate over 70%. In addition to the
      potential public health hazard, the current zoonotic epidemic has caused severe
      economic losses. Efforts must be concentrated on early detection of bird
      outbreaks with aggressive culling, quarantines, and disinfection. To prepare for
      and prevent increased human cases, it is essential to improve detection methods
      and stockpile effective antivirals. Novel therapeutic modalities, including
      short, interfering RNAs and new vaccine strategies that use plasmid-based genetic
      systems offer promise, should a pandemic occur.

PMID- 16566868
TI  - The use of macrolides in treatment of upper respiratory tract infections.
AB  - Antimicrobial resistance is a growing problem among upper respiratory tract
      pathogens. Resistance to beta-lactam drugs among Streptococcus pneumoniae,
      Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and
      well-tolerated antibiotics, macrolides play a key role in the treatment of
      community-acquired upper respiratory tract infections (RTIs). Their broad
      spectrum of activity against gram-positive cocci, such as S. pneumoniae and S.
      pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin),
      and Moraxella catarrhalis, has led to the widespread use of macrolides for
      empiric treatment of upper RTIs and as alternatives for patients allergic to beta
      lactams. Macrolide resistance is increasing among pneumococci and recently among
      S. pyogenes, and is associated with increasing use of the newer macrolides, such
      as azithromycin. Ribosomal target modification mediated by erm(A) and erm(B)
      genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of
      resistance in both S. pneumoniae and S. pyogenes. Recently, ribosomal protein and
      RNA mutations have been found to be responsible for acquired resistance to
      macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides
      are only weakly active against macrolide-resistant streptococci species,
      producing an efflux pump (mef), and are inactive against pathogens with ribosomal
      target modification (erm), treatment failures are uncommon. Therefore, macrolide
      therapy, for now, remains a good alternative for treatment of upper RTIs;
      however, continuous monitoring of the local resistance patterns is essential.

PMID- 16566870
TI  - Epilepsy and chromosomal rearrangements in Smith-Magenis Syndrome
      [del(17)(p11.2p11.2)].
AB  - Smith-Magenis syndrome is a multiple congenital anomalies/mental retardation
      syndrome associated with a heterozygous deletion of chromosome 17p11.2. Seizures
      have not been formally studied in this population. Our objectives were to
      estimate the prevalence of seizures and electroencephalographic (EEG)
      epileptiform abnormalities in patients with Smith-Magenis syndrome with defined
      chromosomal rearrangements and to describe the spectrum of abnormal EEG patterns.
      Prolonged video-EEGs were obtained in 60 patients. Eighteen percent of patients
      reported a seizure history; however, abnormal EEGs were identified in 31 of the
      60 subjects and 27 of 31 were epileptiform. Generalized epileptiform patterns
      were the most common (73%). Most patients with either small or large deletions
      had an abnormal EEG (83%; 75%) in contrast to those with a common deletion (49%).
      Our results indicate that epileptiform EEG abnormalities are frequent in patients
      with Smith-Magenis syndrome. Considering that close to one third of individuals
      with Smith-Magenis syndrome with epileptiform abnormalities also had a history of
      clinical seizures, cortical hyperexcitability and epilepsy should be considered
      an important component of the Smith-Magenis syndrome clinical phenotype.

PMID- 16566871
TI  - Tuberous sclerosis complex: correlation of magnetic resonance imaging (MRI)
      findings with comorbidities.
AB  - We studied the magnetic resonance imaging (MRI) findings in a cohort of Chinese
      children with tuberous sclerosis complex to determine the relationship between
      age, sex, mental retardation, autism, epilepsy, infantile spasm, and early age at
      onset of seizures and the numbers and locations of tubers detected. We searched
      our tuberous sclerosis registry, established in 1985 (N = 44), and performed an
      analysis of children who had MRIs of the brain performed (n = 22). A
      neuroradiologist blinded to the clinical findings scored the MRIs according to
      the total number and site of the tubers. The following factors were analyzed:
      age, sex, presence of autism (n = 7), presence (n = 19) and severity of mental
      retardation (mild [n = 12], moderate to severe [n = 7]), presence of epilepsy (n
      = 21) or infantile spasm (n = 8), and age at onset of seizures less than 1 year
      (n = 10). There was no significant relationship between the number and site of
      tubers and the following factors: sex, autism, mental retardation, degree of
      mental retardation, epilepsy, history of infantile spasm, or age at onset of
      seizures less than 1 year. Only the presence of cortical tubers in the parietal
      regions had a significant relationship with the history of infantile spasm (P =
      .012). Using multiple regression analysis of all of the risk factors, only age is
      related to the number of tubers in the MRI (P = .047), and a history of infantile
      spasm is related to the presence of tubers in the parietal (P = .009) and
      occipital (P = .031) lobes. The associated comorbidities in tuberous sclerosis
      complex might be explained by more complex underlying genetic or pathologic
      issues rather than purely by the site of the cortical tubers. We suggest that a
      developmental approach, by analyzing the age at the appearance of tubers in both
      symptomatic and asymptomatic cases with the development of other neuropsychiatric
      comorbidities, should be undertaken to assess the causal relationship.

PMID- 16566873
TI  - Modafinil for drooling in cerebral palsy.
AB  - Two patients with spastic cerebral palsy recently treated with modafinil at the
      Walter Reed Army Medical Center child neurology clinic have stopped drooling.
      This occurred after starting modafinil for spasticity and without other changes
      in the patients' treatment programs. The decrease in drooling is to a remarkable
      degree. Both patients had a chronic problem with drooling. One patient has gone
      from wearing a bib or bandanna, which was constantly wet from drooling to being
      essentially dry. After starting modafinil, both patients stopped drooling. The
      parents initially observed decreased drooling at home. Clinic appointment
      examinations and evaluations at physical therapy confirmed these observations.
      Better coordination and speech have been noted in each patient. Modafinil
      improves drooling in at least some patients with spastic cerebral palsy. The
      decreased drooling is due to improvements noted in swallowing.

PMID- 16566872
TI  - Increased medial thalamic creatine-phosphocreatine found by proton magnetic
      resonance spectroscopy in children with obsessive-compulsive disorder versus
      major depression and healthy controls.
AB  - Altered brain creatine-phosphocreatine levels might reflect changes in brain
      energy use and have been implicated in the pathogenesis of obsessive-compulsive
      disorder and major depressive disorder. We used proton magnetic resonance
      spectroscopy to measure absolute concentrations of creatine-phosphocreatine in
      the right and left medial thalami in 18 pediatric patients with major depressive
      disorder 9 to 17 years of age, 18 case-matched healthy controls, and 27 patients
      with obsessive-compulsive disorder 7 to 16 years old. The two patient groups were
      psychotropic drug naive and were not comorbid for the diagnosis of the comparison
      group. We found significantly increased left and right medial thalamic creatine
      phosphocreatine concentrations in patients with obsessive-compulsive disorder
      compared with both healthy controls and patients with major depression. Creatine
      phosphocreatine concentrations did not differ significantly between patients with
      major depression and healthy controls. Our data suggest that increased medial
      thalamic creatine-phosphocreatine concentrations in patients with untreated
      obsessive-compulsive disorder reflect altered energy use in the medial thalamus
      and might differentiate patients with obsessive-compulsive disorder from healthy
      controls and patients with major depression. Although these results must be
      considered preliminary, further study of the diagnostic specificity of creatine
      phosphocreatine in obsessive-compulsive disorder is indicated.

PMID- 16566874
TI  - Detection of wallerian degeneration in a newborn by diffusion magnetic resonance
      imaging (MRI).
AB  - We present the case of an infant with hypoxic-ischemic encephalopathy in whom
      wallerian degeneration is demonstrated in white-matter fiber tracts by diffusion
      magnetic resonance imaging (MRI). MRI was undertaken on days 2 and 9 and then at
      9 months of age. On day 2, conventional MRI was normal, but diffusion MRI showed
      bioccipital abnormalities. On day 9, diffusion MRI showed marked abnormalities in
      the deep white matter of the occipital regions (left > right), corpus callosum,
      left posterior limb of the internal capsule, and left cerebral peduncle. Water
      apparent diffusion coefficient values showed a significant reduction in the left
      occipital white matter and corpus callosum between days 2 and 9 while
      demonstrating the expected pseudonormalization in cortical gray matter. Images at
      9 months showed left occipital porencephaly and atrophy of the left cerebral
      peduncle, with the infant displaying right hemiplegia at 18 months of age. In
      this case, the time course of diffusion changes differed between white and gray
      matter, with diffusion MRI showing delayed wallerian degeneration of the cerebral
      white matter. This case characterizes this degeneration with clinical and follow
      up MRI at 9 months of age.

PMID- 16566875
TI  - Behavioral therapy for treatment of stereotypic movements in nonautistic
      children.
AB  - Although typically described in autistic, mentally retarded, and sensory-deprived
      individuals, motor stereotypies also occur in normal children. In this
      preliminary report, the behavior modification techniques of habit reversal and
      differential reinforcement of other behavior were evaluated as a therapeutic
      modality for the suppression of stereotypic movements in nonautistic subjects.
      Twelve children, ages 6 to 14 years, with physiologic stereotypies were treated
      using a standardized treatment protocol. Clinical outcomes were based on
      differences between assessments obtained at baseline and on telephone follow-up.
      Evaluation scales included measures of the frequency, intensity, interference,
      and number of stereotypies (Stereotypy Severity Scale motor portion and
      Stereotypy Linear Analog Scale) and assessment of global function (Child Global
      Assessment Scale and Stereotypy Severity Scale global portion). The results were
      correlated with the child's level of motivation and the number of treatment
      sessions. After a mean follow-up of 12.1 months, motor stereotypies showed
      significant improvement on the Stereotypy Linear Analog Scale and Stereotypy
      Severity Scale total score, P = .009 and P = .046, respectively. Both scales
      showed a relationship between the number of treatment sessions attended and a
      reduction in movements. The Child Global Assessment Scale also improved with
      therapy, but there was no correlation with the number of treatment sessions.
      Highly motivated patients had greater improvement on the Stereotypy Linear Analog
      Scale and Stereotypy Severity Scale scales compared with less motivated patients,
      but motivation had no impact on the Child Global Assessment Scale. The combined
      use of habit reversal and differential reinforcement of other behavior is
      beneficial in reducing motor stereotypies in nonautistic children.

PMID- 16566876
TI  - Infantile spasms as an adverse outcome of neonatal cortical sinovenous
      thrombosis.
AB  - Cerebral sinovenous thrombosis is a rare but potentially serious condition often
      occurring in children with nonspecific presenting features. Much remains to be
      learned about the long-term outcome of infants with cerebral sinovenous
      thrombosis. We report a series of four patients taken from a prospective database
      of neonates with sinovenous thrombosis who subsequently developed infantile
      spasms, three with hypsarrythmia on electroencephalography and one with multiple
      independent spike foci. The first patient presented at 2 weeks of age with
      hypernatremia, dehydration, and seizures. He was found to have extensive
      thrombosis and hemorrhagic infarction of the right basal ganglia. The second
      patient presented at 5 weeks of life and was found to have sagittal sinus
      thrombosis with bilateral intracranial hemorrhage. The third patient presented
      with seizures on day 1 of life and was found to have venous thrombosis involving
      the torcular, extending into the sagittal sinus. The fourth patient presented at
      3 weeks with lethargy and seizures. He was diagnosed with bacterial meningitis
      and also had extensive sinus thrombosis. All patients developed infantile spasms
      at ages 9, 7, 11, and 10 months, respectively. This is the first report in the
      English literature describing infantile spasms as a possible outcome of
      sinovenous thrombosis in early infancy.

PMID- 16566877
TI  - Recurrent headache in chinese children: any agreement between clinician diagnosis
      and symptom-based diagnoses using the International Classification of Headache
      Disorders (Second Edition)?
AB  - There has been a lack of published data on the pattern of recurrent headache in
      Chinese children. The validity of the International Classification of Headache
      Disorders criteria has not been evaluated in Chinese children. We performed a
      retrospective medical record review of 124 children aged <18 years with an
      International Classification of Diseases coding of headache followed up in a
      general outpatient clinic in a university-based hospital over a 3-year period
      (2000-2002). The aims of our study were to (1) study the pattern of recurrent
      headache in Chinese children and (2) study any agreement between clinical
      diagnoses made by our board-certified pediatricians and symptom-based diagnoses
      using the second edition of the International Classification of Headache
      Disorders (International Classification of Headache Disorders-II). The most
      common type was unclassified headache (70.2%), followed by infrequent episodic
      tension-type headache (24.2%) and migraine without aura (5.6%). A family history
      of headache or migraine was more commonly found in children with infrequent
      episodic tension-type headache or migraine without aura (P = .0109). The co
      occurrence of abdominal pain with infrequent episodic tension-type headache was
      30%; for unclassified headache, it was 19.5%. Dysmenorrhea occurred in 7.1% of
      girls with infrequent episodic tension-type headache and 8.6% of girls with
      unclassified headache. However, migraine without aura was not associated with
      abdominal pain or dysmenorrhea. Children with migraine without aura were more
      frequently referred to child neurologists (P = .0207) and admitted (P = .0000).
      Neurologic investigations, including electroencephalography, computed tomography,
      or magnetic resonance imaging of the brain, were performed in less than 30% of
      cases. Abnormal results were found in only seven cases; with two referred to a
      neurosurgeon and none requiring surgical intervention. Thus, by using the
      clinical diagnosis of our board-certified pediatricians as the standard, the
      sensitivity and specificity of International Classification of Headache Disorders
      II-based definition of migraine without aura was 23.1% and 93.4%, respectively,
      and for infrequent episodic tension-type headache, it was 37.5% and 76%,
      respectively. The typical characteristics of migraine tend to emerge later and
      might have led to underdiagnosis of the younger age group, with a higher rate of
      referral and inpatient management. The new edition of the International
      Classification of Headache Disorders criteria is still restrictive in clinical
      practice and might not be able to reflect current pediatric practice. Further
      studies with a defined study period or recurrent headache might be more useful in
      analyzing the use of these new International Classification of Headache Disorders
      criteria in the diagnosis of recurrent headache in children.

PMID- 16566878
TI  - Right hemisphere brain morphology, attention-deficit hyperactivity disorder
      (ADHD) subtype, and social comprehension.
AB  - Social comprehension involves empathy for others' experiences and appropriate
      responses to nonverbal cues. Previous research using magnetic resonance imaging
      (MRI) has suggested a relationship between brain morphology and psychiatric
      syndromes, such as attention-deficit hyperactivity disorder (ADHD), that
      typically entail social difficulties. The right hemisphere, specifically, has
      been associated with social skill deficits, and numerous studies have also
      associated ADHD with social skill deficits. No studies, however, have examined
      the association of ADHD subtype with both social comprehension and right
      hemisphere morphology. Fifty-nine children (6-12 years old) underwent MRI, from
      which the right hemisphere was classified into four morphologic subtypes.
      Children were also grouped by ADHD subtype or clinical control status. From
      Behavior Assessment System for Children (BASC) items, a social comprehension
      subscale was constructed. Analyses revealed significant differences in social
      comprehension based on ADHD subtype. Differences in social comprehension based on
      ADHD status were especially pronounced in children with atypical right-hemisphere
      morphology. Thus, the diagnosis of ADHD might be associated with underlying risk
      in the area of social comprehension, especially for children with atypical right
      hemisphere morphology.

PMID- 16566879
TI  - Nonprogressive familial leukoencephalopathy with porencephalic cyst and focal
      seizures.
AB  - Two siblings with a similar white-matter disease but different clinical symptoms
      are described. The first sibling suffers from nonprogressive spastic hemiparesis
      secondary to a congenital periventricular porencephalic cyst. Her brother has
      focal epilepsy. On magnetic resonance imaging, both patients show diffuse white
      matter involvement predominantly of the posterior periventricular area. We
      suggest that this is a familial white-matter disorder with minimal symptoms and
      no progression in early childhood.

PMID- 16566880
TI  - Coexisting muscular dystrophies and epilepsy in children.
AB  - Muscular dystrophies are composed of a variety of genetic muscle disorders linked
      to different chromosomes and loci and associated with different gene mutations
      that lead to progressive muscle atrophy and weakness. Fukuyama congenital
      muscular dystrophy is frequently associated with partial and generalized epilepsy
      and congenital brain anomalies, including cobblestone complex and other neuronal
      migration defects. We report generalized convulsive epilepsy in a boy with normal
      brain magnetic resonance imaging and Duchenne muscular dystrophy with deletion of
      dystrophin gene, and we report absence epilepsy with normal brain magnetic
      resonance imaging in another boy with limb girdle muscular dystrophy with partial
      calpain deficiency. We, therefore, review coexisting muscular dystrophies and
      epilepsy in children. In addition to Fukuyama congenital muscular dystrophy,
      partial or generalized epilepsy has also been reported in the following types of
      muscular dystrophies, including Duchenne/Becker dystrophy, facioscapulohumeral
      dystrophy, congenital muscular dystrophy with partial and complete deficiency of
      laminin alpha2 (merosin) chain, and limb girdle muscular dystrophy with partial
      calpain deficiency.

PMID- 16566881
TI  - Diagnostic strategy for the detection of dystrophin gene mutations in asian
      patients and carriers using immortalized cell lines.
AB  - Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked recessive
      diseases of muscle degeneration caused by mutations in the dystrophin gene. More
      than half of our local Asian patients have point mutations that cannot be
      detected by conventional multiplex polymerase chain reaction deletion screening.
      This study aimed to develop mutational screening and carrier detection for
      Duchenne and Becker muscular dystrophy using protein truncation analysis from
      Epstein-Barr virus-transformed lymphocyte cell lines. Messenger ribonucleic acid
      was extracted from fresh lymphocytes and Epstein-Barr virus-transformed
      lymphocyte cell lines of 14 patients. Reverse transcriptase polymerase chain
      reaction was performed in 11 overlapping segments, followed by in vitro protein
      translation and truncation analysis. DNA sequencing was carried out for the
      corresponding complementary DNA regions, which showed aberrant truncated protein
      products. Carrier studies using this method were also performed for two families.
      Half of the patients had frame-shifting deletions, and the remaining seven
      patients showed point mutations, of which four were novel. These mutations were
      detected in messenger ribonucleic acid extracted from both fresh lymphocytes and
      Epstein-Barr virus-transformed lymphocyte cell lines. Carrier status was
      confirmed in one family and was found to be negative in the other family studied.
      Protein truncation analysis is an efficient method of screening truncating point
      mutations from immortalized lymphocyte cell lines from patients. This approach
      not only serves to prove the pathogenicity of both deletion- and nondeletion-type
      mutations; it is also effective for carrier detection. The use of such cell lines
      obviates the need for repeated blood and muscle sampling in patients and offers a
      perpetual source of messenger ribonucleic acid that can be used long after the
      patient's demise.

PMID- 16566882
TI  - Sturge-Weber syndrome variant with atypical intracranial findings: case report.
AB  - Sturge-Weber syndrome is characterized by a facial port-wine nevus,
      leptomeningeal angiomatosis, and glaucoma; it is commonly complicated by epilepsy
      and hemiparesis. We present a patient with a head and neck port-wine nevus,
      glaucoma, abnormalities of the intracranial deep veins, and untreated
      communicating hydrocephalus. The patient lacks any radiologic or clinical
      evidence of cerebral leptomeningeal angiomatosis. Considering that intracranial
      venous anomalies also are likely compatible with the embryologic explanation of
      Sturge-Weber syndrome, this child can serve as an unusual example of Sturge-Weber
      syndrome type II.

PMID- 16566883
TI  - Impaired motor control in patients with benign focal epilepsy of childhood.
AB  - Upper extremity motor function was quantitatively assessed in 6 children (age 7
      11 years) treated with antiepileptic drugs for benign focal epilepsies of
      childhood and compared with that of 30 age-matched normal children. Both motor
      performance and adaptation to perturbing mechanical constraints imposed by a
      robotic device were significantly impaired in children with benign focal
      epilepsies of childhood. Our findings thus question whether certain "benign"
      epilepsies are truly benign and whether pharmacologic treatment might contribute
      to motor impairment.

PMID- 16566884
TI  - Oromotor and communication findings in joubert syndrome: further evidence of
      multisystem apraxia.
AB  - This study provides descriptive information in the areas of oromotor abilities
      and communication to better understand the spectrum of disability in individuals
      with Joubert syndrome. Participants included 21 individuals with the diagnosis of
      Joubert syndrome (mean age 10.45 years). Participants completed oromotor and
      receptive language measures. In addition, all of the participants' speech and
      gesture communication from a narrative task was coded and analyzed from
      videotape. Caregivers reported the participants' level of fine and gross motor
      function. The results show that individuals with Joubert syndrome exhibit a
      distinct oromotor pattern consistent with verbal and lingual apraxias. Despite
      significant motor skills deficits and oculomotor apraxia, persons with Joubert
      syndrome produced gestures when communicating, and those whose speech was less
      intelligible used a higher rate of gesture compared with those with greater
      verbal output. These findings suggest a new form of apraxia not previously
      described in the condition and are consistent with previous research that
      suggests that persons with Joubert syndrome typically do not exhibit classic
      symptoms of autism spectrum disorder.

PMID- 16566885
TI  - Parenting stress and its relationship to the behavior of children with Joubert
      syndrome.
AB  - This study describes the relationship between parenting stress and behavior in
      children with Joubert syndrome, a rare genetic neurodevelopmental disorder.
      Parents (N = 43) reported severely impaired child adaptive behaviors. Most
      children did not show maladaptive behaviors, but a subset of approximately 20%
      displayed significant problems in areas such as inattention, overactivity, social
      withdrawal, and atypical behaviors. Mothers (59%) and fathers (40%) reported
      elevated levels of parenting stress. A hierarchical regression, including
      demographics, adaptive behavior, and maladaptive behavior, predicted 67% of the
      variance in mothers' stress and 40% of the variance in fathers' stress.
      Maladaptive behaviors uniquely contributed to maternal and paternal stress. The
      child's adaptive behavior level contributed significantly to parenting stress for
      mothers but not for fathers. Findings provide a better understanding of the
      impact of child behavior on parents caring for a child with Joubert syndrome.

PMID- 16566886
TI  - Fat intolerance in developmentally impaired children with severe feeding
      intolerance.
AB  - Children with a variety of genetic, metabolic, and neurologic disorders can
      suffer from severe feeding intolerance that is unresponsive to medical, surgical,
      and nutritional therapy. Developmentally disabled tube-fed children with severe
      upper gastrointestinal symptoms that persisted after fundoplication who were
      unresponsive to all medical, surgical, and nutritional interventions underwent a
      thorough gastrointestinal evaluation, including gastroscopy, pH-metry, upper
      gastrointestinal barium series, and gastric emptying studies. They were placed on
      a low-fat diet, and the symptoms before and after the diet were compared. The
      patients were then rechallenged with incremental increases in fat until the
      symptoms recurred or the patients reached their former fat concentration. Six
      children meeting the study criteria were evaluated. Four of these patients had a
      significant improvement in symptoms, oral intake and feeding tolerance with a
      decrease in fat intake, and relapse of symptoms when fat calories were increased.
      Improvement occurred in children who had been intolerant to duodenal feeding. We
      were subsequently able to wean two children from tube feeding. Dietary fat can
      provoke upper gastrointestinal symptoms in children with gastric and intestinal
      dysmotility. Short-term manipulation of dietary fat intake can improve tolerance
      to feeding.

PMID- 16566887
TI  - Developmental regression and mitochondrial dysfunction in a child with autism.
AB  - Autistic spectrum disorders can be associated with mitochondrial dysfunction. We
      present a singleton case of developmental regression and oxidative
      phosphorylation disorder in a 19-month-old girl. Subtle abnormalities in the
      serum creatine kinase level, aspartate aminotransferase, and serum bicarbonate
      led us to perform a muscle biopsy, which showed type I myofiber atrophy,
      increased lipid content, and reduced cytochrome c oxidase activity. There were
      marked reductions in enzymatic activities for complex I and III. Complex IV
      (cytochrome c oxidase) activity was near the 5% confidence level. To determine
      the frequency of routine laboratory abnormalities in similar patients, we
      performed a retrospective study including 159 patients with autism (Diagnostic
      and Statistical Manual of Mental Disorders-IV and Childhood Autism Rating Scale)
      not previously diagnosed with metabolic disorders and 94 age-matched controls
      with other neurologic disorders. Aspartate aminotransferase was elevated in 38%
      of patients with autism compared with 15% of controls (P <.0001). The serum
      creatine kinase level also was abnormally elevated in 22 (47%) of 47 patients
      with autism. These data suggest that further metabolic evaluation is indicated in
      autistic patients and that defects of oxidative phosphorylation might be
      prevalent.

PMID- 16566888
TI  - Central core disease: atypical case with respiratory insufficiency in an
      intensive care unit.
AB  - Central core disease is a rare congenital myopathy characterized by formation of
      typical cores in myofibrils. We report an atypical case of central core disease
      with respiratory insufficiency in the late stage of congenital myopathy. A 13
      year-old girl was admitted to the intensive care unit with the diagnosis of
      respiratory distress syndrome. Ventilatory support was initiated. After 2 weeks
      of follow-up, the Division of Pediatric Neurology was consulted owing to the
      failure to wean her from the ventilator. Clinical and electromyographic features
      were in favor of primary muscle disease. Muscle biopsy revealed typical cores in
      type 1 muscle fibers, which were diagnostic for central core disease. This case
      was presented to emphasize that patients with respiratory distress who cannot be
      weaned from the ventilator should be evaluated for central core disease with an
      atypical presentation.

PMID- 16566889
TI  - Congenital indifference to pain and deletion of chromosome 10q-: new association.
AB  - We describe a case of a de novo terminal deletion of the long arm of chromosome
      10 with the novel feature of congenital indifference to pain in a 2-year 10-month
      old boy. Relative indifference to pain defined by a lack of emotional response to
      pain has not been described previously in association with the terminal deletion
      of the long arm of chromosome 10.

PMID- 16566890
TI  - Inosiplex affects the spectra of proton magnetic resonance spectroscopy in
      subacute sclerosing panencephalitis.
AB  - In vivo magnetic resonance techniques such as magnetic resonance imaging (MRI)
      and magnetic resonance spectroscopy have been some of the most useful tools for
      evaluation of neurologic diseases. In subacute sclerosing panencephalitis,
      magnetic resonance spectroscopy can be an additional tool for evaluation of
      disease progression or the efficacy of the treatment, such as interferon or
      inosiplex, compared with MRI. Inosiplex is one of the effective drugs for
      subacute sclerosing panencephalitis, but our in vivo and in vitro magnetic
      resonance spectroscopic study indicated that inosiplex affects the spectra,
      suggesting a possible failure of neurologic evaluation in a patient with subacute
      sclerosing panencephalitis treated with inosiplex.

PMID- 16566891
TI  - Influence on grip of knife handle surface characteristics and wearing protective
      gloves.
AB  - Ten subjects were asked to apply maximum torques on knife handles with either
      their bare hand or their hand wearing a Kevlar fibre protective glove. Four knife
      handles (2 roughnesses, 2 hardnesses) were tested. Surface electromyograms of 6
      upper limb and shoulder muscles were recorded and subject opinions on both knife
      handle hardness and friction in the hand were also assessed. The results revealed
      the significant influence of wearing gloves (p<0.0001), knife type (p<0.0005) and
      handle hardness (p<0.005) on the applied torque. Wearing Kevlar fibre gloves
      greatly increased the torque independently of the other two parameters. Under the
      bare hand condition, a 90 degrees ShA slightly rough handle provided the greatest
      torque. Subject opinion agreed with the observed effects on recorded torque
      values except for the hardness factor, for which a preference for the 70 degrees
      ShA value over the 90 degrees ShA value emerged.

PMID- 16566892
TI  - Requirement of proper occlusal force for morphological maturation of neural
      components of periodontal Ruffini endings of the rat incisor.
AB  - The present study examined the effect of reduced occlusal force on morphological
      maturation of periodontal Ruffini endings, primary mechanoreceptors in the
      periodontal ligament, of the rat incisor. The reduction of occlusal force was
      induced by grinding the cutting edges of unilateral incisors of the rat from
      postnatal day 14 (PN14d), when periodontal Ruffini endings are immature. Under
      normal development, the axon terminals of Ruffini endings gradually ramified with
      the passage of time, and showed ruffled outlines having numerous dot-like
      structures around PN28d. When the mechanical stimulation was reduced, appearance
      of dot-like structures at the axon terminals delayed. Quantitative analysis
      elucidated that the percentages of immunoreactive areas for protein gene product
      9.5, a marker protein of neural elements, at ground side were significantly
      smaller than those at non-ground side 14 days following the initial grinding. The
      distribution and morphology of terminal Schwann cells was not apparently
      affected. The present results indicate that the proper mechanical stimulation to
      the ligament contributes to the morphological maturation of the periodontal
      Ruffini endings.

PMID- 16566893
TI  - Applications of ATR-FTIR spectroscopic imaging to biomedical samples.
AB  - FTIR spectroscopic imaging in ATR (Attenuated Total Reflection) mode is a
      powerful tool for studying biomedical samples. This paper summarises recent
      advances in the applications of ATR-FTIR imaging to dissolution of pharmaceutical
      formulations and drug release. The use of two different ATR accessories to obtain
      chemical images of formulations in contact with water as a function of time is
      demonstrated. The innovative use of the diamond ATR accessory allowed in situ
      imaging of tablet compaction and dissolution. ATR-FTIR imaging was also applied
      to obtain images of the surface of skin and the spatial distribution of protein
      and lipid rich domains was obtained. Chemical images of cross-section of rabbit
      aorta were obtained using a diamond ATR accessory and the possibility of in situ
      imaging of arterial samples in contact with aqueous solution was demonstrated for
      the first time. This experiment opens an opportunity to image arterial samples in
      contact with solutions containing drug molecules. This approach may help in
      understanding the mechanisms of treatment of atherosclerosis.

PMID- 16566895
TI  - Subtype-specific, bi-component inhibition of SK channels by low internal pH.
AB  - The effects of low intracellular pH (pH(i) 6.4) on cloned small-conductance Ca2+
      activated K+ channel currents of all three subtypes (SK1, SK2, and SK3) were
      investigated in HEK293 cells using the patch-clamp technique. In 400 nM internal
      Ca2+ [Ca2+]i, all subtypes were inhibited by pH(i) 6.4 in the order of
      sensitivity: SK1>SK3>SK2. The inhibition increased with the transmembrane
      voltage. In saturating internal Ca2+, the inhibition was abolished for SK1-3
      channels at negative potentials, indicating a [Ca2+]i-dependent mode of
      inhibition. Application of 50 microM 1-ethyl-2-benzimidazolone was able to
      potentiate SK3 current to the same extent as at neutral pH(i). We conclude that
      SK1-3 all are inhibited by low pH(i). We suggest two components of inhibition: a
      [Ca2+]i-dependent component, likely involving the SK beta-subunits calmodulin,
      and a voltage-dependent component, consistent with a pore-blocking effect. This
      pH(i)-dependent inhibition can be reversed pharmacologically.

PMID- 16566894
TI  - Membrane transport of hydrogen peroxide.
AB  - Hydrogen peroxide (H2O2) belongs to the reactive oxygen species (ROS), known as
      oxidants that can react with various cellular targets thereby causing cell damage
      or even cell death. On the other hand, recent work has demonstrated that H2O2
      also functions as a signalling molecule controlling different essential processes
      in plants and mammals. Because of these opposing functions the cellular level of
      H2O2 is likely to be subjected to tight regulation via processes involved in
      production, distribution and removal. Substantial progress has been made
      exploring the formation and scavenging of H2O2, whereas little is known about how
      this signal molecule is transported from its site of origin to the place of
      action or detoxification. From work in yeast and bacteria it is clear that the
      diffusion of H2O2 across membranes is limited. We have now obtained direct
      evidence that selected aquaporin homologues from plants and mammals have the
      capacity to channel H2O2 across membranes. The main focus of this review is (i)
      to summarize the most recent evidence for a signalling role of H2O2 in various
      pathways in plants and mammals and (ii) to discuss the relevance of specific
      transport of H2O2.

PMID- 16566896
TI  - Inhibition of hepatitis C virus RNA replication by short hairpin RNA synthesized
      by T7 RNA polymerase in hepatitis C virus subgenomic replicons.
AB  - RNA interference (RNAi) is a cellular process that induces gene silencing by
      which small duplexes of RNA specifically target a homologous sequence for
      cleavage by cellular ribonucleases. Here, to test the RNAi method for blocking
      hepatitis C virus (HCV) RNA replication, we created four short hairpin RNAs
      (shRNAs) targeting the HCV internal ribosome entry site/Core gene transcript
      using T7 RNA polymerase. shRNA suppressed the replication of HCV RNA in the HCV
      replicon. On the other hand, short interfering RNAs synthesized using the T7 RNA
      polymerase system trigger a potent induction of interferon-alpha and -beta in a
      variety of cells. We examined whether the shRNAs synthesized using the T7 RNA
      polymerase system activated double-stranded RNA-dependent protein kinase, 2'-5'
      oligoadenylate synthetase, or interferon-regulatory factor-3. Our results
      demonstrated that the T7-transcribed shRNA did not activate these proteins in Huh
      7 cells and the HCV replicon. These shRNAs are a promising new strategy for anti
      HCV gene therapeutics.

PMID- 16566897
TI  - Estrogen deficient male mice develop compulsive behavior.
AB  - BACKGROUND: Aromatase converts androgen to estrogen. Thus, the aromatase knockout
      (ArKO) mouse is estrogen deficient. We investigated the compulsive behaviors of
      these animals and the protein levels of catechol-O-methyltransferase (COMT) in
      frontal cortex, hypothalamus and liver. METHODS: Grooming was analyzed during the
      20-min period immediately following a water-mist spray. Running wheel activity
      over two consecutive nights and barbering were analyzed. COMT protein levels were
      measured by Western analysis. RESULTS: Six-month old male but not female ArKO
      mice develop compulsive behaviors such as excessive barbering, grooming and wheel
      running. Excessive activities were reversed by 3 weeks of 17beta-estradiol
      replacement. Interestingly, the presentation of compulsive behaviors is
      accompanied by concomitant decreases (p < .05) in hypothalamic COMT protein
      levels in male ArKO mice. These values returned to normal upon 17beta-estradiol
      treatment. In contrast, hepatic and frontal cortex COMT levels were not affected
      by the estrogen status, indicating region- and tissue-specific regulation of COMT
      levels by estrogen. No differences in COMT levels were detectable between female
      animals of both genotypes. CONCLUSIONS: This study describes the novel
      observation of a possible link between estrogen, COMT and development of
      compulsive behaviors in male animals which may have therapeutic implications in
      obsessive compulsive disorder (OCD) patients.

PMID- 16566898
TI  - Neuropsychological performance in first-episode adolescents with schizophrenia: a
      comparison with first-episode adults and adolescent control subjects.
AB  - BACKGROUND: The goal of this study was to compare the extent of cognitive
      deficits between adolescents and adults early in the course of schizophrenia.
      METHODS: A comprehensive neuropsychological battery was performed on 49
      adolescents with childhood- or adolescent-onset schizophrenia, 139 adults with
      adult-onset schizophrenia, 32 healthy adolescent volunteers, and 240 healthy
      adult volunteers. Both patient groups were assessed early in the course of their
      illness and were matched to their respective control groups on age and parental
      education. RESULTS: The adolescent patients performed significantly worse than
      the adult patients on tasks of working memory, language, and motor function. The
      healthy adolescents also performed significantly worse than the healthy adults in
      working memory and language tasks but were significantly better than the adults
      in motor function. When accounting for developmental differences in the control
      group, only motor performance was worse in the adolescent patients compared with
      the adult patients. CONCLUSIONS: These findings, when coupled with published
      retrospective studies reporting greater cognitive deficits in earlier onset
      schizophrenia, implicate a cessation in development in specific cognitive domains
      following the onset of schizophrenia in adolescent patients.

PMID- 16566899
TI  - The mesolimbic dopamine reward circuit in depression.
AB  - The neural circuitry that mediates mood under normal and abnormal conditions
      remains incompletely understood. Most attention in the field has focused on
      hippocampal and frontal cortical regions for their role in depression and
      antidepressant action. While these regions no doubt play important roles in these
      phenomena, there is compelling evidence that other brain regions are also
      involved. Here we focus on the potential role of the nucleus accumbens (NAc;
      ventral striatum) and its dopaminergic input from the ventral tegmental area
      (VTA), which form the mesolimbic dopamine system, in depression. The mesolimbic
      dopamine system is most often associated with the rewarding effects of food, sex,
      and drugs of abuse. Given the prominence of anhedonia, reduced motivation, and
      decreased energy level in most individuals with depression, we propose that the
      NAc and VTA contribute importantly to the pathophysiology and symptomatology of
      depression and may even be involved in its etiology. We review recent studies
      showing that manipulations of key proteins (e.g. CREB, dynorphin, BDNF, MCH, or
      Clock) within the VTA-NAc circuit of rodents produce unique behavioral
      phenotypes, some of which are directly relevant to depression. Studies of these
      and other proteins in the mesolimbic dopamine system have established novel
      approaches to modeling key symptoms of depression in animals, and could enable
      the development of antidepressant medications with fundamentally new mechanisms
      of action.

PMID- 16566900
TI  - Mineralocorticoid receptor function in posttraumatic stress disorder after
      pretreatment with metyrapone.
AB  - BACKGROUND: Alterations of mineralocorticoid receptor (MR) mediated negative
      feedback inhibition of cortisol might contribute to abnormalities of hypothalamic
      pituitary adrenal (HPA) activity in posttraumatic stress disorder (PTSD).
      METHODS: In a placebo-controlled study, we examined 11 subjects with PTSD and 11
      healthy controls between 14:00 and 21:00. After pretreatment with 3 g metyrapone
      to inhibit basal endogenous cortisol secretion, subjects orally received in
      randomized order .5 mg of the MR agonist fludrocortisone or placebo.
      Adrenocorticotropic hormone (ACTH), cortisol, and 11-deoxycortisol were measured
      every 30 min until 21:00. RESULTS: Compared to placebo, fludrocortisone led to a
      significant decrease of ACTH and cortisol that was similar in both groups.
      Subjects with PTSD had higher raw cortisol and higher normed (baseline-related)
      ACTH and 11-deoxycortisol values after metyrapone independent of treatment with
      fludrocortisone or placebo. CONCLUSIONS: While HPA responses after metyrapone
      seem to be stronger in PTSD compared to controls, no alterations of
      mineralocorticoid receptor function in PTSD were found in this study.

PMID- 16566901
TI  - Prevention of missing data in clinical research studies.
AB  - Missing data is a problem that is ubiquitous to all clinical studies and a source
      of multiple problems from an analytic point of view (reduced statistical power,
      increased the type I error, bias) Statistical approaches have been developed to
      analyze data collected from trials with missing data. Understanding and
      implementing the appropriate statistical technique is essential but should be
      differentiated from preventive approaches that are designed to reduce rates of
      missing data In this article, we draw attention to these preventive efforts.
      Seven steps to minimizing the amount of missing data are defined as
      documentation, training, monitoring reports, patient contact, data entry and
      management, pilot studies, and communication. Although the implementation of
      these approaches is time consuming and costly, the overall quality of the study
      is increased. Despite efforts devoted to areas, no study is without missing data.
      Once the study is completed, it is essential to assess the pattern of missing
      data and apply the appropriate statistical analysis.

PMID- 16566902
TI  - Puzzling out the reeler brainteaser: does reelin signal to unique neural
      lineages?
AB  - Much has been learnt about the reeler mutant since its inclusion in the
      celebrated Catalog of the Neurological Mutants of the Mouse in the mid-sixties.
      The pace of discovery was most definitively agitated after the identification of
      reelin, the genuine gene product mutated in reeler (first expressed by a
      monolayer of cells in the marginal zone of the developing brain), and the
      subsequent establishment of the so-called reelin signaling pathway (including the
      reelin receptor machinery expressed by migrating newborn neurons). Yet little is
      known as to how the reelin signaling events, which are critically involved in
      neuronal migration, are linked to the in vivo behavior of individual neurons.
      Lately, the results of the forced ectopic expression of reelin in the neurogenic
      zone jeopardized all proposed models regarding its mechanism of action. Our
      studies suggest that earlier than newborn neurons, the radial glia neuronal
      progenitors may receive a functional reelin signal. Here I show evidence of an
      enriched localization of the reelin receptor machinery in radial glial cells of
      the lateral, but not the median, ganglionic eminence. This precise
      compartmentalization suggests that, unlike radial migration of cortical
      projection neurons, reelin signaling is not directly related with the tangential
      migration of the bulk of cortical interneurons. I hereby submit a personal
      glimpse of reeler morphogenesis which embodies a testable hypothesis; namely,
      that reelin signals to unique neural lineages to regulate migration.

PMID- 16566903
TI  - Characterization of cerebral tissue by MRI map ISODATA in embolic stroke in rat.
AB  - ISODATA using MRI parameter-weighted images has been previously employed to
      characterize ischemic cell damage after stroke in rats. In an effort to increase
      the objectivity and to further automate the ISODATA, MRI parameter maps were now
      employed. Male Wistar rats were subjected to embolic stroke and received
      treatment via a femoral vein at 4 h post-stroke. The control rats received saline
      and were sacrificed at 6, 24 and 48 h after stroke, respectively. Treated rats
      received rtPA alone or were treated with a combination of rtPA and an antibody,
      7E3 F(ab')2, against the glycoprotein receptor that binds the platelet to fibrin.
      These rats were sacrificed at 24, or 48, h post-stroke. T1, T2 and diffusion maps
      were employed for map ISODATA analysis. H&E histological analysis of coronal
      sections of tissue was performed and compared with map ISODATA from the
      corresponding sections. ISODATA signatures were highly correlated (R
      approximately 0.80, P < 0.0001) with the ischemic cell damage analyzed at 6, 24
      and 48 h post-stroke. At 24 and 48 h after stroke, ISODATA lesion sizes were
      highly correlated (R > 0.97, P < 0.001) with lesion sizes measured
      histologically. The combination treatment of rtPA and 7E3 F(ab')2 reduced both
      infarction size (P < 0.002) and average signature (P < 0.03) at 48 h after
      stroke, compared to saline-treated animals. No significant difference was found
      between saline and rtPA-alone-treated rats. The map ISODATA successfully provides
      objective and automated quantitation of the ischemic damage in both size and
      severity in an embolic stroke model of rat with and without a therapeutic
      intervention.

PMID- 16566904
TI  - Estradiol and progesterone modulation of angiotensin II receptors in the arcuate
      nucleus of ovariectomized and lactating rats.
AB  - The expression of angiotensin II (Ang II) receptors in the brain is modulated by
      estradiol and progesterone. Considering that Ang II plays a critical role in
      controlling prolactin secretion and that neurons in the arcuate nucleus (ARC) are
      the main regulator of this function, the present study aimed to evaluate ARC Ang
      II receptor binding in 2 experimental models with different estradiol and
      progesterone plasma levels. Animals were divided into 4 groups: ovariectomy (OVX)
      plus oil vehicle, OVX plus estradiol and progesterone replacement, lactating rats
      on day 7 postpartum, and lactating rats on day 20. Animals were killed by
      decapitation, and the brains were removed. Ang II receptors were quantified by
      autoradiography in ARC. Trunk blood samples were collected, and plasma estradiol
      and progesterone were measured by radioimmunoassay. Treatment of OVX rats with
      estradiol and progesterone increased Ang II receptor binding when compared to OVX
      vehicle-treated animals. Plasma estradiol (r = +0.77) and progesterone (r =
      +0.87) were highly correlated with Ang II receptors in ovariectomized animals.
      Lactating rats (day 20) showed a significant decrease in Ang II receptor binding
      and plasma progesterone when compared to lactating rats (day 7), however, no
      difference was seen in plasma estradiol. Plasma levels of progesterone (r =
      +0.81), but not estradiol (r = +0.32), were highly correlated with Ang II
      receptors in lactating rats. In conclusion, present results show that ARC Ang II
      receptors decreases on day 20 of lactation compared to day 7 and are highly
      correlated with plasma progesterone, indicating a pivotal role for progesterone
      in this regulation.

PMID- 16566905
TI  - Paraoxon suppresses Ca(2+) spike and afterhyperpolarization in snail neurons:
      Relevance to the hyperexcitability induction.
AB  - The effects of organophosphate (OP) paraoxon, active metabolite of parathion,
      were studied on the Ca(2+) and Ba(2+) spikes and on the excitability of the
      neuronal soma membranes of land snail (Caucasotachea atrolabiata). Paraoxon (0.3
      muM) reversibly decreased the duration and amplitude of Ca(2+) and Ba(2+) spikes.
      It also reduced the duration and the amplitude of the afterhyperpolarization
      (AHP) that follows spikes, leading to a significant increase in the frequency of
      Ca(2+) spikes. Pretreatment with atropine and hexamethonium, selective blockers
      of muscarinic and nicotinic receptors, respectively, did not prevent the effects
      of paraoxon on Ca(2+) spikes. Intracellular injection of the calcium chelator
      BAPTA dramatically decreased the duration and amplitude of AHP and increased the
      duration and frequency of Ca(2+) spikes. In the presence of BAPTA, paraoxon
      decreased the duration of the Ca(2+) spikes without affecting their frequency.
      Apamin, a neurotoxin from bee venom, known to selectively block small conductance
      of calcium-activated potassium channels (SK), significantly decreased the
      duration and amplitude of the AHP, an effect that was associated with an increase
      in spike frequency. In the presence of apamin, bath application of paraoxon
      reduced the duration of Ca(2+) spike and AHP and increased the firing frequency
      of nerve cells. In summary, these data suggest that exposure to submicromolar
      concentration of paraoxon may directly affect membrane excitability. Suppression
      of Ca(2+) entry during the action potential would down regulate Ca(2+)-activated
      K(+) channels leading to a reduction of the AHP and an increase in cell firing.

PMID- 16566906
TI  - Effects of melatonin on orphanin FQ/nociceptin-induced hyperalgesia in mice.
AB  - The pain modulatory properties of melatonin (MT) are generally recognized but the
      detail of the interaction between melatonin and opioid system in pain regulation
      is not fully understood. The present study was undertaken to investigate the
      modulatory effect of melatonin (MT) on the hyperalgesic effect of Orphanin
      FQ/Nociceptin (OFQ/NC, NC), a member of opioid peptide family.
      Intracerebroventricular (i.c.v.) administration of NC (10 microg/mouse) induced
      significant hyperalgesic effect in tail-flick test in mice; i.c.v. (5, 10, 50
      microg/mouse) or intraperitoneal (i.p.) (5, 10, 50 mg/kg) co-injection of
      melatonin dose-dependently reversed NC-induced hyperalgesia and showed a profound
      analgesic effect. The antihyperalgesia effect of MT could be significantly
      antagonized by i.c.v. co-injection of luzindole (10 microg/mouse) (an antagonist
      of MT receptor) or naloxone (10 microg/mouse) (antagonist of traditional opioid
      receptor). Taken together, all the results suggested that MT could produce a
      luzindole and naloxone sensitive reversing effect on NC-induced hyperalgesia at
      supraspinal and peripheral level in mice. The augmentation effect of MT on the
      traditional opioid system may be one of the mechanisms of this antihyperalgesia
      action induced by MT. The present work will help to elucidate the mechanism of
      the pain modulation effect of MT, and also will help to represent new interesting
      modulating therapeutic targets for the relief of pain.

PMID- 16566907
TI  - Neuronal cytoskeleton and synaptic densities are altered after a chronic
      treatment with the cannabinoid receptor agonist WIN 55,212-2.
AB  - Cannabinoid CB1 receptors are the most abundant G-protein-coupled receptors in
      the brain. Its presynaptic location suggests a role for cannabinoids in
      modulating the release of neurotransmitters from axon terminals by retrograde
      signaling. The neuroprotective effects of cannabinoid agonists in animal models
      of ischemia, seizures, hypoxia, Multiple Sclerosis, Huntington and Parkinson
      disease have been demonstrated in several reports. The proposed mechanism for the
      neuroprotection ranges from antioxidant effects, reduction of microglial
      activation and anti-inflammatory reaction to receptor-mediated reduction of
      glutamate release. In the present work, we analyzed the morphological changes
      induced by a chronic treatment with the synthetic cannabinoid receptor agonist,
      WIN 55,212-2, in four brain regions where the CB1 cannabinoid receptor is present
      in high density: the CA1 hippocampal area, corpus striatum, cerebellum and
      frontal cortex. After a twice-daily treatment for 14 days with the cannabinoid
      receptor agonist (3 mg/kg sc, each dose) to male Wistar rats (150-170 g), the
      expression of neurofilaments (Nf-160 and Nf-200), microtubule-associated protein
      2 (MAP-2), synaptophysin (Syn) and glial fibrillary acidic protein (GFAP) was
      studied by immunohistochemistry and digital image analysis. Ultrastructural study
      of the synapses was done using electron microscopy. After the treatment, a
      significant increase in the expression of neuronal cytoskeletal proteins (Nf-160,
      Nf-200, MAP-2) was observed, but we did not find changes in the expression of
      GFAP, the main astroglial cytoskeletal protein. In cerebellum, there was an
      increase in Syn expression and in the number of synaptic vesicles, while, in the
      hippocampus, an increase in the Syn expression and in the thickness of the
      postsynaptic densities was observed. The results obtained from these studies
      provide evidences on the absence of astroglial reaction and a sprouting phenomena
      induced by the WIN treatment that might be a key contributor to the long-term
      neuroprotective effects observed after cannabinoid treatments in different models
      of central nervous system (CNS) injury reported in the literature.

PMID- 16566908
TI  - Expression of thymosin beta in the rat brain following transient global ischemia.
AB  - Thymosin beta (Tbeta) isoforms play an important role in the organization of the
      cytoskeleton by sequestering G-actin during development of the mammalian brain.
      In this study, we examined changes in the expression of Tbeta4 and Tbeta15 after
      transient global ischemia. Tbeta15 mRNA increased gradually in the dentate gyrus
      (DG) of the hippocampal formation from 3 h after reperfusion and peaked 9 h
      later. Similarly, a significant increase in Tbeta4 mRNA level was observed in the
      DG 12 h after reperfusion. Tbeta4 and Tbeta15 proteins were found in different
      cell types in control brains; Tbeta15 was expressed in a subset of doublecortin
      (DCX)-positive cells in the DG, whereas Tbeta4-IR was observed in DG neurons and
      nearby microglial cells. After ischemia, Tbeta15-IR was found in DG neurons and
      Tbeta4-IR in the reactivated microglial cells. Interestingly, Tbeta15-IR
      accumulated in the nuclei of CA1 neurons, which are vulnerable to ischemic
      insults. These results suggest that Tbeta4 and Tbeta15 function in different
      cellular contexts during ischemia-induced responses.

PMID- 16566909
TI  - Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase
      activity during early reperfusion.
AB  - OBJECTIVES: We previously demonstrated that ischemic preconditioning (IPC)
      attenuates calpain activation during reperfusion. Herein, we tested the
      hypothesis that enhancement of Na+/K+-ATPase activity during early reperfusion as
      a result of calpain inhibition is involved in the protection afforded by
      myocardial IPC. METHODS: Intracellular Na+ concentration ([Na+]i) measured using
      23Na-magnetic resonance spectroscopy, Na+/K+-ATPase activity, detachment of
      Na+/K+-ATPase alpha subunits from the membrane cytoskeleton, degradation of
      fodrin and ankyrin, and calpain activation were analysed in isolated rat hearts
      reperfused after 60 min of ischemia with or without previous IPC and different
      treatments aimed to mimic or blunt the effects of IPC. RESULTS: In non-treated
      hearts subjected to ischemia (control hearts), reperfusion for 5 min severely
      reduced Na+/K+-ATPase activity and dissociated alpha1 and alpha2 subunits of
      Na+/K+-ATPase from the membrane-cytoskeleton complex in parallel with proteolysis
      of alpha-fodrin and ankyrin-B and calpain activation. IPC accelerated the
      recovery of [Na+]i, increased Na+/K+-ATPase activity, and prevented dissociation
      of Na+/K+-ATPase from the membrane-cytoskeleton complex. IPC also prevented alpha
      fodrin and ankyrin-B loss and calpain activation, effects that were associated
      with attenuated lactate dehydrogenase (LDH) release and infarct size and improved
      contractile recovery. These effects of IPC were reproduced by perfusing the
      hearts with the calpain inhibitor MDL-28170 and by transient stimulation of cAMP
      dependent protein kinase (PKA) with CPT-cAMP, and they were reverted by perfusing
      with the PKA inhibitor H89. CONCLUSION: The results of the present study are
      consistent with the hypothesis that enhanced recovery of Na+/K+-ATPase activity
      during reperfusion as a result of attenuated calpain-mediated detachment of the
      protein from the membrane-cytoskeleton complex contributes to the protection
      afforded by IPC.

PMID- 16566910
TI  - Cardiac genomic response following preconditioning stimulus.
AB  - This review focuses on the genomic response following a preconditioning stimulus.
      Initial studies demonstrated that classical ischemic preconditioning mediated by
      cyclic episodes of short durations of reversible ischemia and reperfusion could
      result in the reprogramming of gene expression. Some of these genes are
      translated into proteins during the late preconditioning or so-called "second
      window of protection". Subsequent studies determined a unique similarity of the
      expressed gene profiles between diverse varieties of preconditioning including
      ischemic/hypoxic, heat shock, and oxidative stress. The most common genes that
      are expressed by virtually any kind of stress conditioning include antioxidants
      like superoxide dismutase, glutathione peroxidase and heme oxygenase and heat
      shock proteins such as HSP70. At a later date, differential display and
      subtractive hybridization techniques revealed the identities of many other genes
      including those belonging to mitochondrial respiratory chain such as ATPases.
      More recently, gene array profiles using gene chips determined several other
      genes triggered by preconditioning including the mitochondrial genes. The results
      of the studies present in the literature clearly indicate the existence of a
      strong resemblance between the patterns of gene expression profiles induced by
      diverse preconditioning stimuli, oxidative stress being situated at the cross
      roads of all forms of the stresses. Redox signaling appears to be responsible for
      the conversion of the ischemia/reperfusion-induced "death signal" into
      preconditioning-mediated "survival signal".

PMID- 16566911
TI  - Elastin biosynthesis: The missing link in tissue-engineered blood vessels.
AB  - Nearly 20 years have passed since Weinberg and Bell attempted to make the first
      tissue-engineered blood vessels. Following this early attempt, vascular tissue
      engineering has emerged as one of the most promising approaches to fabricate
      orderly and mechanically competent vascular substitutes. In elastic and muscular
      arteries, elastin is a critical structural and regulatory matrix protein and
      plays an important and dominant role by conferring elasticity to the vessel wall.
      Elastin also regulates vascular smooth muscle cells activity and phenotype.
      Despite the great promise that tissue-engineered blood vessels have to offer,
      little research in the last two decades has addressed the importance of elastin
      incorporation into these vessels. Although cardiovascular tissue engineering has
      been reviewed in the past, very little attention has been given to elastin. Thus,
      this review focuses on the recent advances made towards elastogenesis and the
      challenges we face in the quest for appropriate functional vascular substitutes.

PMID- 16566912
TI  - Spectrin-phospholipid interactions. Existence of multiple kinds of binding sites?
AB  - The object of this paper is to review briefly the studies on the interactions of
      erythroid and non-erythroid spectrins with lipids in model and natural membranes.
      An important progress on the identification of lipid-binding sites has recently
      been made although many questions remain still unanswered. In particular, our
      understanding of the physiological role of such interactions is still limited.
      Another important issue is the occurrence of spectrins in membrane rafts, how
      they are attached to the raft and what is their function in rafts.

PMID- 16566913
TI  - Separate Na,K-ATPase genes are required for otolith formation and semicircular
      canal development in zebrafish.
AB  - We have investigated the role of Na,K-ATPase genes in zebrafish ear development.
      Six Na,K-ATPase genes are differentially expressed in the developing zebrafish
      inner ear. Antisense morpholino knockdown of Na,K-ATPase alpha1a.1 expression
      blocked formation of otoliths. This effect was phenocopied by treatment of
      embryos with ouabain, an inhibitor of Na,K-ATPase activity. The otolith defect
      produced by morpholinos was rescued by microinjection of zebrafish alpha1a.1 or
      rat alpha1 mRNA, while the ouabain-induced defect was rescued by expression of
      ouabain-resistant zebrafish alpha1a.1 or rat alpha1 mRNA. Knockdown of a second
      zebrafish alpha subunit, alpha1a.2, disrupted development of the semicircular
      canals. Knockdown of Na,K-ATPase beta2b expression also caused an otolith defect,
      suggesting that the beta2b subunit partners with the alpha1a.1 subunit to form a
      Na,K-ATPase required for otolith formation. These results reveal novel roles for
      Na,K-ATPase genes in vestibular system development and indicate that different
      isoforms play distinct functional roles in formation of inner ear structures. Our
      results highlight zebrafish gene knockdown-mRNA rescue as an approach that can be
      used to dissect the functional properties of zebrafish and mammalian Na,K-ATPase
      genes.

PMID- 16566914
TI  - Neurofascin interactions play a critical role in clustering sodium channels,
      ankyrin G and beta IV spectrin at peripheral nodes of Ranvier.
AB  - The Ig cell adhesion molecules (CAM) neurofascin (NF) and Nr-CAM are localized at
      developing nodes of Ranvier in peripheral myelinated axons prior to clustering of
      Na+ channels. Different isoforms of NF are expressed on neurons and glia, and NF
      binding on both cells has been suggested to play roles in node and paranode
      formation. To clarify the role of NF further, we analyzed effects of NF-Fc fusion
      proteins in Schwann cell-DRG neuron myelinating cocultures. NF-Fc significantly
      inhibited nodal clustering of Na+ channels, ankyrin G, and betaIV spectrin, and
      modestly reduced Caspr clustering at paranodal junctions; it did not
      significantly affect lengths or numbers of myelin-positive segments, axon initial
      segments, or accumulations of phosphorylated-ERM proteins in Schwann cell nodal
      microvilli. NF-Fc binds to Schwann cells but little or no binding to DRG neurons
      was detected. The results suggest a critical early role for axonal NF in
      clustering of Na+ channels at nodes of Ranvier via interactions with receptors on
      Schwann cells.

PMID- 16566915
TI  - Development of the male germline stem cell niche in Drosophila.
AB  - Stem cells are found in specialized microenvironments, or "niches", which
      regulate stem cell identity and behavior. The adult testis and ovary in
      Drosophila contain germline stem cells (GSCs) with well-defined niches, and are
      excellent models for studying niche development. Here, we investigate the
      formation of the testis GSC niche, or "hub", during the late stages of
      embryogenesis. By morphological and molecular criteria, we identify and follow
      the development of an embryonic hub that forms from a subset of anterior somatic
      gonadal precursors (SGPs) in the male gonad. Embryonic hub cells form a discrete
      cluster apart from other SGPs, express several molecular markers in common with
      the adult hub and organize anterior-most germ cells in a rosette pattern
      characteristic of GSCs in the adult. The sex determination genes transformer and
      doublesex ensure that hub formation occurs only in males. Interestingly, hub
      formation occurs in both XX and XY gonads mutant for doublesex, indicating that
      doublesex is required to repress hub formation in females. This work establishes
      the Drosophila male GSC niche as a model for understanding the mechanisms
      controlling niche formation and initial stem cell recruitment, as well as the
      development of sexual dimorphism in the gonad.

PMID- 16566916
TI  - Neurogenic secretion mediated by the purinergic P2Y1 receptor in guinea-pig small
      intestine.
AB  - We tested the hypothesis that ATP is an enteric neurotransmitter that acts at
      P2Y1 excitatory purinergic receptors on intestinal secretomotor neurons to evoke
      neurogenic mucosal secretion in the guinea pig. Ussing chamber methods for
      studying neurogenic intestinal secretion were used to test the hypothesis.
      Application of ATP evoked concentration-dependent increases in short circuit
      current (Isc) indicative of stimulation of electrolyte secretion. MRS2179, a
      selective P2Y1 purinergic receptor antagonist, suppressed the ATP-evoked
      responses in a concentration-dependent manner with an IC50 of 0.9+/-0.1 microM.
      Tetrodotoxin or a selective vasoactive intestinal peptide (VPAC1) receptor
      antagonist suppressed or abolished the ATP-evoked responses. A selective VPAC1
      receptor antagonist also suppressed Isc responses evoked by electrical field
      stimulation of the secretomotor neurons. Secretory responses to ATP were not
      suppressed by scopolamine, piroxicam nor selective adenosine receptor
      antagonists. Region-specific differences in responses to ATP corresponded to
      regional differences in the expression of mRNA transcripts for the P2Y1 receptor.
      Post-receptor signal transduction for the P2Y1-evoked responses involved
      stimulation of phospholipase C and an IP3/Ca2+-calmodulin/protein kinase C
      signaling cascade. Our evidence suggests that ATP is released as a
      neurotransmitter to stimulate neurogenic mucosal secretion by binding to P2Y1
      receptors expressed by VIP-ergic secretomotor neurons.

PMID- 16566917
TI  - Effect of YM-254890, a specific Galphaq/11 inhibitor, on experimental peripheral
      arterial disease in rats.
AB  - The protective effect of YM-254890, a specific Galphaq/11 inhibitor, on laurate
      induced peripheral arterial disease in rats was compared with those of
      prostaglandin E1 (PGE1), beraprost, and clopidogrel. YM-254890 inhibited ADP
      induced ex vivo rat platelet aggregation at a dose of 3 microg/kg. Furthermore,
      YM-254890 strongly inhibited phenylephrine-, serotonin- and endothelin-1-induced
      contractions in the rat aorta, and improved dermal blood flow after the laurate
      injection. The intra-arterial single bolus administration of YM-254890 15 min
      after the laurate injection dose-dependently inhibited the progression of the
      lesion, with significance, at 3 microg/kg without affecting systemic blood
      pressure. PGE1 and beraprost, when administered before the laurate injection,
      were effective, but their potencies were less than that of YM-254890. Clopidogrel
      significantly suppressed lesion progression when administered at 30 mg/kg twice a
      day for 3 days, which completely inhibited platelet aggregation. These results
      suggest that the local administration of YM-254890 may be useful for treating
      peripheral arterial disease.

PMID- 16566918
TI  - Activation of the adenylyl cyclase/protein kinase A pathway facilitates neural
      release of beta-nicotinamide adenine dinucleotide in canine mesenteric artery.
AB  - Using high performance liquid chromatography techniques with fluorescence
      detection we demonstrate that overflow of beta-nicotinamide adenine dinucleotide
      evoked by electrical field stimulation (16 Hz, 0.3 ms) in the canine isolated
      mesenteric artery is increased by the activators of adenylyl cyclase (AC)
      forskolin and calcitonin gene-related peptide (CGRP), by dibutyryl cAMP, and by
      the inhibitors of phosphodiesterases III and IV milrinone and rolipram. The
      enhancing effect of forskolin is abolished by the AC inhibitor MDL 12,330A and by
      protein kinase A (PKA) inhibitors peptide 14-22 amide and 4-cyano-3
      methylisoquinoline. Therefore, activation of the AC/cAMP/PKA pathway enhances the
      release of beta-NAD+ from perivascular nerve terminals.

PMID- 16566919
TI  - Nitric oxide synthase mediates delta opioid receptor-induced hypothermia in rats.
AB  - The role of nitric oxide (NO) production in delta opioid receptor-induced
      hypothermia has not been reported. The present study investigated the effect of
      nitric oxide synthase (NOS) inhibitors on the hypothermic effect of (+)-4-[(aR)-a
      ((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N
      diethylbenzamide (SNC-80), a nonpeptide delta opioid agonist. SNC-80 (35 mg/kg,
      i.p.) administered to rats caused a significant hypothermia. N-nitro-L-arginine
      methyl ester (L-NAME) (10, 25 and 50 mg/kg, i.p.), a NOS inhibitor, and 7
      nitroindazole (7-NI) (5 and 10 mg/kg, i.p.), a neuronal NOS inhibitor, were
      ineffective. For combined administration, L-NAME (50 mg/kg, i.p.) or 7-NI (10
      mg/kg, i.p.) attenuated SNC-80-evoked hypothermia. To determine the involvement
      of central NOS, L-NAME (0.25, 0.5 and 1 mg/rat) was administered i.c.v. 30 min
      prior to SNC-80 (35 mg/kg, i.p.). Experiments revealed that L-NAME (1 mg/rat,
      i.c.v.) attenuated SNC-80-induced hypothermia. The present data demonstrate that
      central NO production is necessary for delta opioid receptor-induced hypothermia.

PMID- 16566920
TI  - Expression dynamics of drug resistance genes, multidrug resistance 1 (MDR1) and
      lung resistance protein (LRP) during the evolution of overt leukemia in
      myelodysplastic syndromes.
AB  - It is well-known that leukemic cells of overt leukemia (OL) that have transformed
      from myelodysplastic syndromes (MDS) are more resistant to chemotherapy as
      compared with de novo AML cells. Thus, to examine the expression levels of drug
      resistant genes and their alterations with the development of OL in MDS, the
      expression of mRNA for MDR1 and LRP was determined in bone marrow samples from
      control, de novo AML, MDS, MDS at the time of OL transformation (MDS --> OL), and
      after transformation (OL) by quantitative real-time RT-PCR. The expression of
      MDR1 in MDS bone marrow at the time of initial diagnosis was as low as that for
      control subjects. However, the expression level was significantly elevated at the
      time of the development of OL (MDS --> OL) compared with the initial MDS subjects
      (P < 0.05), while expression was relatively reduced after OL development (OL).
      The expression of LRP was significantly higher in MDS and MDS --> OL samples than
      control subjects. However, the high expression of LRP in MDS --> OL was
      significantly reduced after OL development (OL). The expression levels of drug
      resistant genes in MDS --> OL or OL were not significantly higher than those of
      de novo AML samples, although LRP expression in MDS or MDS --> OL was relatively
      higher than that of de novo AML. Detecting increases in the expression of MDR1
      would be useful for predicting OL development in MDS patients.

PMID- 16566921
TI  - Regulation of bcl-2 expression by Ubc9.
AB  - Posttranslational modifications mediated by ubiquitin-like proteins have been
      implicated in regulating a variety of cellular pathways. Although small ubiquitin
      like modifier (SUMO) is a new member of this family, it has caught a great deal
      of attention recently because of its novel and distinguished functions.
      Sumoylation is a multiple-step process, involving maturation, activation,
      conjugation and ligation. Ubc9 is an E2 conjugating enzyme essential for
      sumoylation. We have previously shown that suppression of sumoylation by a
      dominant negative Ubc9 mutant (Ubc9-DN) in the estrogen receptor (ER) positive
      MCF-7 cells is associated with alterations of tumor cell's response to anticancer
      drugs as well as tumor growth in a xenograft mouse carcinoma model. To dissect
      the underlying mechanism of Ubc9-associated alterations of drug responsiveness
      and tumor growth, we profiled gene expression for the cells expressing wild type
      Ubc9 (Ubc9-WT) and Ubc9-DN. We found that several tumorigenesis-related genes
      were downregulated in the Ubc9-DN cells. Within this group, we found that over 10
      genes are known to be regulated by ER. Experiments using the estrogen response
      element fused to the luciferase reporter showed that the basal level of
      luciferase activity was significantly reduced in the Ubc9-DN cells when compared
      to the vector alone or the Ubc9-WT cells. Furthermore, we found that both the
      stability and the subcellular localization of steroid hormone receptor
      coactivator-1 (SRC-1) were altered in the Ubc9-DN cells. Together, these results
      suggest that Ubc9 might regulate bcl-2 expression through the ER signaling
      pathway, which ultimately contributes to the alterations of drug responsiveness
      and tumor growth.

PMID- 16566922
TI  - XIAP decreases caspase-12 cleavage and calpain activity in spinal cord of ALS
      transgenic mice.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by the selective
      degeneration of motor neurons. The cause for nerve cell demise is not clear but
      involves activation of the caspase family of cysteine proteases. We have shown
      that ER stress and caspase-12 activation occur in ALS transgenic mice carrying
      the mutant copper/zinc superoxide dismutase (SOD1) gene. In these mice, we found
      that the antiapoptotic proteins, X-linked Inhibitor of Apoptosis Protein (XIAP)
      and the related protein, MIAP2 were decreased. To study the role of this, we
      generated double transgenic mice expressing XIAP in ALS spinal cord neurons using
      the Thy1 promoter. Overexpression of XIAP inhibited caspase-12 cleavage and
      reduced calpain activity in the ALS mice. XIAP also reduced the breakdown of
      calpastatin that is an inhibitor of calpain. In the double transgenic mice, life
      span was increased by about 12%. These data support the view that XIAP has
      beneficial effects in ALS and extends survival. The neuroprotective effect of
      XIAP involves inhibition of caspases and the stabilization of the
      calpastatin/calpain system that is altered in the ALS mice.

PMID- 16566923
TI  - The glycoprotein hGC-1 binds to cadherin and lectins.
AB  - Human granulocyte colony stimulating factor stimulated clone-1 (hGC-1, also known
      as GW112, OLM4, and hOlfD) is an olfactomedin-related glycoprotein of unknown
      function. We performed a series of biochemical studies to characterize its
      function. Using hGC-1 purified from baculovirus Sf9 cells we demonstrated that
      hGC-1 is a secreted glycoprotein containing N-linked carbohydrate chains and
      forms disulfide-bonded multimers. It binds to cell surfaces and to the locutions
      ricinus communis agglutinin I, concanavalin A and wheat germ agglutinin. Purified
      hGC-1 enhanced NIH3T3 and 293T/17 cell spreading and attachment, as did hGC-1
      enriched culture supernatants of 293T/17 cells transfected with an hGC-1
      expression vector. Coimmunoprecipitation studies demonstrated that hGC-1
      interacts with cadherin in 293T/17 cells. This interaction depends on the C
      terminal olfactomedin domain, but does not require the five well-conserved
      cysteine residues. However, cysteine residues at 83, 85, 246 and 437 are
      essential for secretion, and cysteine 226 is critical for hGC-1 multimer
      formation. Our studies demonstrated that hGC-1, an extracellular matrix
      glycoprotein, facilitates cell adhesion. Its potential interaction with
      endogenous cell surface lectins and cadherin may mediate this function.

PMID- 16566924
TI  - Identification of new central nervous system specific mouse microRNAs.
AB  - MicroRNAs (miRNAs) are small regulatory molecules suppressing mRNA activity in
      metazoans. Here we describe two new miRNAs cloned from brain tissue of mouse
      embryos. These miRNAs are expressed mainly during embryogenesis and specifically
      in the central nervous system. We also established the expression patterns of
      three recently identified miRNAs that were found in our short RNA library. All of
      them were expressed in the brain and spinal chord but while miR-410 and miR-431
      were central nervous system specific, miR-500 was also expressed in limb buds. In
      addition, the expression of miR-500 in limb buds showed very strong asymmetry in
      favour of the left hand side.

PMID- 16566925
TI  - Spatially dependent activation of the patterning protease, Easter.
AB  - The dorsoventral axis of the Drosophila embryo is established by the activating
      cleavage of a signaling ligand by a serine protease, Easter, only on the ventral
      side of the embryo. Easter is the final protease in a serine protease cascade in
      which initial reaction steps appear not to be ventrally restricted, but where
      Easter activity is promoted ventrally through the action of a spatial cue at an
      unknown step in the pathway. Here, biochemical studies demonstrate that this
      spatial control occurs at or above the level of Easter zymogen activation, rather
      than through direct promotion of Easter's catalytic activity against the
      signaling ligand.

PMID- 16566926
TI  - Inhibition of human matriptase by eglin c variants.
AB  - Based on the enzyme specificity of matriptase, a type II transmembrane serine
      protease (TTSP) overexpressed in epithelial tumors, we screened a cDNA library
      expressing variants of the protease inhibitor eglin c in order to identify potent
      matriptase inhibitors. The most potent of these, R(1)K(4)'-eglin, which had the
      wild-type Pro(45) (P1 position) and Tyr(49) (P4' position) residues replaced with
      Arg and Lys, respectively, led to the production of a selective, high affinity
      (K(i) of 4nM) and proteolytically stable inhibitor of matriptase. Screening for
      eglin c variants could yield specific, potent and stable inhibitors to matriptase
      and to other members of the TTSP family.

PMID- 16566927
TI  - Synaptotagmin I and Ca(2+) promote half fusion more than full fusion in SNARE
      mediated bilayer fusion.
AB  - Synaptic membrane fusion, which is necessary for neurotransmitter release, may be
      mediated by SNAREs and regulated by synaptotagmin (Syt) and Ca(2+). Fusion of
      liposomes mediated by reconstituted SNAREs produces full fusion and hemifusion, a
      membrane structure in which outer leaflets are mixed but the inner leaflets
      remain intact. Here, using the liposome fusion assay, it is shown that Syt
      promoted both hemifusion and full fusion in a Ca(2+)-dependent manner. Syt.Ca(2+)
      increased hemifusion more than full fusion, modulating the ratio of hemifusion to
      full fusion. Unlike the case of neuronal SNAREs, stimulation of fusion by
      Syt.Ca(2+) was not seen for other SNAREs involved in trafficking in yeast,
      indicating that the Syt.Ca(2+) stimulation was SNARE-specific. We constructed
      hybrid SNAREs in which transmembrane domains were swapped between neuronal and
      yeast SNAREs. With these hybrid SNAREs, we demonstrated that the interaction
      between the SNARE motifs of neuronal proteins and Syt.Ca(2+) was required for the
      stimulation of fusion.

PMID- 16566928
TI  - Post-transcriptional downregulation of sarcolipin mRNA by triiodothyronine in the
      atrial myocardium.
AB  - Thyroid hormone-mediated positive cardiotropic effects are differently regulated
      between the atria and ventricles. This regulation is, at least in part, dependent
      on sarcoplasmic reticulum (SR) proteins. Sarcolipin, a homologue of
      phospholamban, has been recently identified as an atrium-specific SR protein. The
      expression of sarcolipin mRNA was significantly decreased in the atria of mice
      with hyperthyroidism and in 3,5,3'-triiodo-l-thyronine-treated neonatal rat
      atrial myocytes. Promoter activity and mRNA stability analyses revealed that
      thyroid hormone post-transcriptionally down regulated the expression of
      sarcolipin mRNA. The atrium-specific effect of thyroid hormone may occur in part
      through the regulation of atrial sarcolipin gene expression.

PMID- 16566929
TI  - Prokaryotic and eukaryotic monothiol glutaredoxins are able to perform the
      functions of Grx5 in the biogenesis of Fe/S clusters in yeast mitochondria.
AB  - The Saccharomyces cerevisiae monothiol glutaredoxin Grx5 participates in the
      mitochondrial biogenesis of iron-sulfur clusters. Grx5 homologues exist in
      organisms from bacteria to humans. Chicken (cGRX5) and human (hGRX5) homologues
      contain a mitochondrial targeting sequence, suggesting a mitochondrial
      localization for these two proteins. We have compartmentalized the Escherichia
      coli and Synechocystis sp. homologues, and also cGRX5 and hGRX5, in the
      mitochondrial matrix of a yeast grx5 mutant. All four heterologous proteins
      rescue the defects of the mutant. The chicken cGRX5 gene was significantly
      expressed throughout the embryo stages in different tissues. These results
      underline the functional conservation of Grx5 homologues throughout evolution.

PMID- 16566930
TI  - Expression of aromatase (P450 aromatase/CYP19) in peritoneal and ovarian
      endometriotic tissues and deep endometriotic (adenomyotic) nodules of the
      rectovaginal septum.
AB  - We found, by reverse transcription--real time--polymerase chain reaction, that
      the expression of aromatase (CYP19) in ovarian, peritoneal endometriosis, and
      deep endometriotic nodules is significantly different, which strengthens the
      theory of three distinct clinical entities. Compared with peritoneal
      endometriosis, ovarian endometriosis exhibits an 8-fold higher expression of
      aromatase, which suggests that aromatase inhibitors may be particularly active in
      this form of endometriosis.

PMID- 16566931
TI  - Sperm immobilizing properties of lemon juice.
AB  - The aim of this study was to evaluate the sperm-immobilizing properties of lemon
      juice to determine if they are consistent with its traditional contraceptive use.
      It was found that lemon juice supernatant (LJS) has high osmolality (550-60 mOsm)
      and low pH (2.2-2.6) and that addition of LJS to semen to give a final
      concentration of 20% v/v reduced the pH from around 8.4 to 4.1. This
      acidification was associated with irreversible cessation of all sperm movements
      within 1 minute. In conclusion, lemon juice should be further evaluated for
      acceptability, safety, and efficacy as a topical vaginal contraceptive agent.

PMID- 16566932
TI  - Intracytoplasmic sperm injection may lead to vertical transmission, expansion,
      and de novo occurrence of Y-chromosome microdeletions in male fetuses.
AB  - Y-chromosome microdeletion in male fetuses conceived by intracytoplasmic sperm
      injection (ICSI) was screened by polymerase chain reaction for sequence-tagged
      sites in azoospermia factor (AZF)-b and AZFc regions. Treatment with ICSI may
      lead to vertical transmission, expansion, and de novo Y-chromosome microdeletion
      in male fetuses.

PMID- 16566933
TI  - Type of menopause, patterns of hormone therapy use, and hot flashes.
AB  - OBJECTIVE: To examine the associations between the type of menopause (natural,
      hysterectomy with ovarian conservation, and hysterectomy with bilateral
      oophorectomy) and the experiencing of hot flashes while accounting for different
      patterns of hormone therapy (HT) use among the menopausal groups. DESIGN: Cross
      sectional study. SETTING: Women who reported their history of hot flashes and HT
      use through a mailed survey. PATIENT(S): Postmenopausal women ages 40-60 years
      residing in the Baltimore metropolitan area. INTERVENTION(S): No interventions
      were administered. MAIN OUTCOME MEASURE(S): Associations between type of
      menopause and the experiencing of hot flashes. RESULT(S): Among all participants,
      both types of surgical menopause were associated with a decreased risk of
      experiencing any, moderate or severe, and daily hot flashes. After taking into
      account HT use patterns, women who underwent bilateral oophorectomy were at
      increased risk of experiencing any, moderate or severe, and daily hot flashes
      compared with women with natural menopause, although only the results for
      moderate or severe hot flashes were statistically significant. Women who
      underwent hysterectomy with ovarian conservation remained at significantly lower
      odds of experiencing any hot flashes than women with natural menopause.
      CONCLUSION(S): Women who undergo bilateral oophorectomy and who are not given HT
      to prevent the onset of menopausal symptoms are at increased risk of experiencing
      hot flashes, especially those that are moderate to severe in nature, compared
      with women with natural menopause.

PMID- 16566934
TI  - Elevated serum mullerian-inhibiting substance may be a marker for ovarian
      hyperstimulation syndrome in normal women undergoing in vitro fertilization.
AB  - We identified patients who experienced ovarian hyperstimulation syndrome (OHSS)
      (n = 16) and compared their baseline pretreatment levels of mullerian-inhibiting
      substance (MIS) to age- and weight-matched patients with normal responses to
      gonadotropins (n = 14). Baseline serum MIS in patients with OHSS were sixfold
      higher than those seen in normal controls (3.62 +/- 0.87 vs. 0.63 +/- 0.09 ng/mL;
      P=.0036), indicating that MIS could potentially serve as a useful marker for
      identifying patients at risk for OHSS.

PMID- 16566935
TI  - Impact of coasting in patients undergoing controlled ovarian stimulation with the
      gonadotropin-releasing hormone antagonist cetrorelix.
AB  - Coasting is the most popular modality for the prevention of ovarian
      hyperstimulation syndrome, but this procedure has not been evaluated in patients
      undergoing controlled ovarian hyperstimulation (COH) with GnRH antagonists. The
      impact of coasting in a cycle in which GnRH antagonist is used was evaluated in
      29 women, and it was found that coasting did not deleteriously affect the outcome
      in high-responder patients undergoing COH with GnRH antagonists.

PMID- 16566936
TI  - Impact of hypnosis during embryo transfer on the outcome of in vitro
      fertilization-embryo transfer: a case-control study.
AB  - OBJECTIVE: To investigate whether hypnosis during ET contributes to successful
      IVF/ET outcome. DESIGN: Case-control clinical study. SETTING: Academic Fertility
      and IVF Unit, Soroka Medical Center, Beer-Sheva, Israel. PATIENT(S): Infertile
      couples undergoing IVF. INTERVENTION(S): Ninety-eight IVF/ET cycles with hypnosis
      during the ET procedure were matched with 96 regular IVF/ET cycles. MAIN OUTCOME
      MEASURES: Comparison of clinical pregnancy and implantation rates between the two
      groups. RESULT(S): We obtained 52 clinical pregnancies out of 98 cycles (53.1%)
      with an implantation rate of 28% among hypnosis IVF/ET cycles, and 29 out of 96
      (30.2%) clinical pregnancies and an implantation rate of 14.4% in the control
      cycles. Our overall IVF program pregnancy rate for the same period was 32.1%.
      Logistic regression analysis was performed emphasizing the positive contribution
      of hypnosis to the IVF/ET conception rates. CONCLUSION(S): This study suggests
      that the use of hypnosis during ET may significantly improve the IVF/ET cycle
      outcome in terms of increased implantation and clinical pregnancy rates.
      Furthermore, it seems that the patients' attitude to the treatment was more
      favorable.

PMID- 16566937
TI  - Determination of lignin by size exclusion chromatography using multi angle laser
      light scattering.
AB  - A method was developed using high-performance size exclusion liquid
      chromatography (HPSEC) with multi-angle laser light scattering (MALLS), quasi
      elastic light scattering (QELS), interferometric refractometry (RI) and UV
      detection to characterize and monitor lignin. The combination proved very
      effective at tracking changes in molecular conformation of lignin molecules over
      time; i.e. changes in molecular weight distribution, radius of gyration, and
      hydrodynamic radius. Until this study, UV detection (280 nm) had been the primary
      lignin determination method for chromatography. Three different HPLC columns were
      used to study the effects of pH, flow conditions, and mobile phase compositions
      (dimethyl sulphoxide, water, 0.1M NaOH, and lithium bromide) on the
      chromatography of lignin. Since light scattering accuracy is highly dependent on
      solute concentration, both the UV and RI detectors were calibrated for use as
      concentration detectors. Shodex Asahipak GS-320 HQ column with 0.1M NaOH (pH
      12.0) run at 0.5 ml/min was found to give the highest separation and most
      consistent recovery. The study also revealed that the lignin aggregated at pH
      below 8.5. This aggregation was detected only by MALLS and was not observed on UV
      or RI detectors. It is very important to take this loss in apparent concentration
      due to aggregation into consideration before collecting reliable depolymerization
      data.

PMID- 16566938
TI  - The C-terminal TPR domain of Tom70 defines a family of mitochondrial protein
      import receptors found only in animals and fungi.
AB  - In fungi and animals the translocase in the outer mitochondrial membrane (TOM
      complex) consists of multiple components including the receptor subunit Tom70.
      Genome sequence analyses suggest no Tom70 receptor subunit exists in plants or
      protozoans, raising questions about its ancestry, function and the importance of
      its activity. Here we characterise the relationships within the Tom70 family of
      proteins. We find that in both fungi and animals, a conserved domain structure
      exists within the Tom70 family, with a transmembrane segment followed by 11
      tetratricopeptide repeat motifs organised in three distinct domains. The C
      terminal domain of Tom70 is highly conserved, and crucial for the import of
      hydrophobic substrate proteins, including those with and those without N-terminal
      presequences. Tom70 likely arose after fungi and animals diverged from other
      eukaryote lineages including plants, and subsequent gene duplication gave rise to
      a paralogue specific to the Saccharomyces group of yeasts. In animals and in
      fungi, Tom70 plays a fundamental role in the import of precursor proteins, by
      assisting relatively hydrophobic regions of substrate proteins into the
      translocation channel in the outer mitochondrial membrane. Proteins that function
      equivalently to Tom70 may have arisen independently in plants and protists.

PMID- 16566939
TI  - Correlation of SF-12 and SF-36 in a trauma population.
AB  - BACKGROUND: The SF-36 is a commonly used general measure of health-related
      quality of life (QoL). The SF-12 is a related tool with less response burden, but
      its performance in a general trauma population is unknown. HYPOTHESIS: The SF-12
      would provide similar QoL information to the SF-36 in blunt trauma patients.
      METHODS: Adults with nonneurological blunt injury were prospectively enrolled.
      Demographic, injury, and socioeconomic data were collected. Patients were
      assessed with functional and psychologic questionnaires 1 and 6 months after
      injury. Physical (PCS) and mental (MCS) component scores of the SF-36 and SF-12
      were compared using Pearson's correlation coefficient. Linear regression
      identified factors associated with the SF-12 and SF-36 PCS and MCS.
      Responsiveness to change was assessed using the standardized response mean.
      RESULTS: Correlation of the PCS was 0.924 and MCS was 0.925 (both P < 0.001). QoL
      remained below population norms at 6 months. PCS was moderately responsive to
      change and was equivalent using either the SF-12 or the SF-36. MCS was not
      responsive to change using either tool. At both time points, at least 25% of
      patients with normal SF-12 PCS or MCS had SF-36 subscale scores significantly
      below the normal population. CONCLUSIONS: The SF-12 can be used to assess QoL in
      trauma patients. The lack of responsiveness to change of the MCS suggests other
      methods may be necessary to fully evaluate mental QoL. Summary scores may not be
      sufficient to fully assess QoL in this population. Combining the SF-12 with
      measures to assess psychosocial variables should be further investigated.

PMID- 16566940
TI  - Isolated perfusion of a tubed superficial epigastric flap in a rodent model.
AB  - BACKGROUND: Isolated perfusion models can yield important data regarding
      metabolism of the skin. An effective model must remain stable during perfusion
      but respond appropriately to metabolic and vascular stimuli. We describe the
      design and characterization of a tubed superficial epigastric isolated perfusion
      flap. MATERIALS AND METHODS: Tubed superficial epigastric flaps were created in
      20 male Sprague Dawley rats. Forty-eight hours later the femoral vessels were
      cannulated and the flaps were perfused using a Krebs-Heinseleit buffer containing
      albumin for a period of 2 h. In five of the flaps norepinephrine and
      acetylcholine were added sequentially to the perfusate to determine vascular
      reactivity. In a further four flaps insulin (20 U/liter) and iodoacetate (5 mM)
      were added to the perfusate to confirm that the flap was metabolically active and
      reactive. Venous outflow was collected at regular intervals and analyzed for
      electrolytes, lactate, and glucose content. Vascularity and skin perfusion were
      characterized using barium microangiography and methylene blue dye injection.
      RESULTS: This flap model was found to be stable in terms of arterial pressure,
      electrolyte levels, and lactate production over the perfusion period.
      Norepinephrine caused a sharp increase in vascular resistance, which was reversed
      by administration of acetylcholine. Lactate production increased appropriately
      with the addition of insulin to the perfusate with a rapid decline following
      addition of the glycolysis inhibitor iodoacetate. There was no leakage of
      perfusate or significant swelling of the flap during the perfusion. CONCLUSIONS:
      The tubed superficial epigastric artery flap makes an effective model for
      isolated perfusion studies of the skin with a wide range of experimental
      applications.

PMID- 16566942
TI  - Mycophenolate mofetil impairs the integrity of colonic anastomosis.
AB  - BACKGROUND: The aim of this experimental study was to investigate the effect of
      mycophenolate mofetil (MMF) during the three phases of colonic anastomosis
      healing and specifically to check the effect of MMF on the expression of
      transforming growth factor-beta1 (TGF-beta1), one of the most important growth
      factors contributing to mechanical stability of colonic anastomosis. MATERIALS
      AND METHODS: Sixty male Wistar rats underwent colonic resection and end-to-end
      anastomosis. The animals were divided into two groups, a study group given MMF 40
      mg/kg, intraduodenally and a control group given vehicle. The rats were
      sacrificed at 3, 7, and 14 days (10 animals in each group). The anastomoses were
      tested by measuring bursting pressure and hydroxyproline content. Histological
      examination and immunohistochemical expression of TGF-beta1 also were assessed.
      RESULTS: The mean bursting pressure in the study group was significantly lower on
      day 3 and 7, but there was no statistical significance on day 14. The mean
      hydroxyproline content was lower in the study group on days 3, 7, and 14.
      Histology showed decreased number of macrophages and fibroblasts on days 3 and 7
      but no difference on day 14. The expression of TGF-beta1 was significantly
      reduced in the study group, with the difference being more pronounced on days 3
      and 7. CONCLUSION: MMF weakens the integrity of colonic anastomosis, and this
      effect is more significant during the inflammatory phase of healing. MMF has a
      negative effect on macrophages and TGF-beta1 expression, resulting in decreased
      collagen accumulation at the anastomosis.

PMID- 16566941
TI  - Transplantation of endothelial progenitor cells transferred by vascular
      endothelial growth factor gene for vascular regeneration of ischemic flaps.
AB  - BACKGROUND: Neovascularization occurs through two mechanisms: angiogenesis and
      vasculogenesis. Therefore, there are two strategies to promote
      neovascularization: therapeutic angiogenesis and therapeutic vasculogenesis
      (endothelial progenitor cells therapy). MATERIALS AND METHODS: In this study, we
      examined whether or not endothelial progenitor cells combined with vascular
      endothelial growth factor (VEGF) gene therapy is useful for ischemia surgical
      flaps in vivo. At the same time, we quantitatively compared the
      neovascularization ability of transplanted endothelial progenitor cells (EPCs)
      transducted with VEGF165 gene and EPCs alone. EPCs were isolated from cord blood
      of healthy human volunteers, cultured in vitro for 7 days and identified by
      immunofluorescence. After transduced with VEGF165 gene in vitro, proliferative
      activity of EPCs was assessed using MTT assay. CM-DiI was used to trace EPCs in
      vivo 4 days after injection of 5 x 10(5) VEGF-transduced EPCs(VEGF-transduced
      EPCs group, n = 10), 5 x 10(5) EPCs (non-transduced EPCs group, n = 10) in 500
      microL EBM-2 media, or 500 microL EBM-2 media (EBM-2 media group, n = 10) local,
      a cranially based flap was elevated on the back of nude mice. The percent flap
      survival, neovasculariztion and blood flow recovery of flaps was detected.
      RESULTS: EPCs expressed cell markers CD34, KDR, and CD133. A statistically
      significant increase in percent flap survival was observed in mice of VEGF
      transduced EPCs group as compared with that of non-transduced EPCs group: 67.99
      +/- 6.64% versus 59.43 +/- 4.69% (P < 0.01), and 41.24 +/- 2.44% in EBM-2 media
      group (P < 0.01). The capillary density and blood flow recovery of flaps in VEGF
      transduced EPCs group were both improved. CM-DiI-labeled VEGF-transduced EPCs
      were observed in vivo and the numbers of cells increased. CONCLUSION: EPCs from
      human cord blood can increased neovascularization of ischemic flaps and augmented
      the survival areas, and VEGF-transduced EPCs have more powerful ability of
      promoting neovascularization in animal model of ischemic flaps.

PMID- 16566943
TI  - Pulse low dose steroids attenuate post-cardiopulmonary bypass SIRS; SIRS I.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) initiates inflammation that contributes
      to multiorgan dysfunction (SIRS). Steroids have been demonstrated to attenuate
      this response; however, resistance to use steroids remains because of potential
      adverse effects of the high doses used. This study examines a lower dose steroid
      protocol for safety and attenuation of SIRS. METHODS: Sixty patients undergoing
      CPB were randomized to pulse low doses of methylprednisolone (250 mg given twice
      IV) or placebo in this RCT. Outcomes pertaining to hemodynamics, ventilator
      requirement, arrhythmia, and metabolic derangements were recorded. Post-operative
      glucose control and gastrointestinal prohylaxis was instituted in all patients.
      RESULTS: IL-6 concentrations were lower in the steroid group at 4 and 8 h post
      operatively (P < 0.0001). The steroid group demonstrated more normothermia (37.2
      degrees C versus 37.6 degrees C, P = 0.002), better hemodynamic stability with
      less requirement for inotropes or vasopressors (0% versus 27.6%, P = 0.005),
      higher SVRIs (1840 versus 1340 DSm2/cm5, P = 0.002), and higher mean arterial
      pressures (79 versus 74 mmHg, P = 0.03). The steroid group had a shorter duration
      of intubation (7.7 versus 10.7 h, P = 0.02), a shorter length of ICU stay (1.0
      versus 2.0 days, P = 0.03), and less blood loss (505 versus 690 ml, P = 0.04)
      with no difference in post-operative blood glucose levels or complications.
      CONCLUSIONS: Patients undergoing cardiopulmonary bypass receiving low pulse dose
      steroids had better hemodynamics, shorter mechanical ventilation times, less
      blood loss, and required less time in the ICU compared to those receiving
      placebo. Therefore, this study demonstrates that prophylactic low dose steroids
      attenuate the SIRS response to CPB without resulting in any untoward side
      effects.

PMID- 16566944
TI  - Injury in the first year of life: risk factors and solutions for high-risk
      families.
AB  - BACKGROUND: Injury is one of the leading causes of death for infants younger than
      1 year of age. We investigated potential contributing factors for injury among
      children born to high-risk families. METHODS: The Fragile Families and Child
      Wellbeing Study is a longitudinal cohort of approximately 5000 children from
      mostly unwed parents across the United States. Data from interviews with mothers
      conducted shortly after birth and follow-up surveys at 1 year were used for this
      analysis. Injuries sustained in the first year of life that required medical
      attention were studied. Multivariate regression analysis was used to identify
      independent risk factors for injury in this population. RESULTS: A total of 13.7%
      of mothers reported that their child had sustained an injury in the first year of
      life. We identified 17 potential maternal, paternal, and environmental risk
      factors for injury, including socioeconomic, mental health, relationship
      violence, criminal justice system involvement, and substance abuse challenges.
      Multivariate regression analyses revealed two significant independent risk
      factors, maternal alcohol use (odds ratio 2.15, P = 0.044) and mother spanking
      child in the previous month (odds ration 2.32, P = 0.027). CONCLUSIONS: Among
      this higher-risk group, injury in the first year of life is more than twice the
      national incidence. Predisposing factors to injury often are complex and
      interrelated, but with focused education and prevention efforts, including
      discussions of maternal alcohol use and attitudes toward physical discipline, we
      may decrease the burden of infant injury in this vulnerable population.

PMID- 16566945
TI  - Bilateral infarcts in the territory of the superior cerebellar artery: clinical
      presentation, presumed cause, and outcome.
AB  - BACKGROUNDS AND PURPOSE: The aim of this study was to document the clinical
      presentation, vascular topographic patterns, stroke mechanism, and outcome of
      bilateral infarcts in the territory of the superior cerebellar artery (SCA) based
      on data collected from a prospective acute stroke registry. METHODS: We studied
      the clinical and radiological features of 11 patients with bilateral infarctions
      in the territory of the SCA diagnosed by brain MRI. RESULTS: Bilateral SCA
      infarcts represented 23.4% (11/47) of all SCA territory infarction. Bilateral SCA
      infarcts mostly associated with brainstem (n = 5), cerebral (n = 5), or non-SCA
      cerebellar lesions (n = 4). The most common clinical presentation at onset was
      sudden fall with axial lateropulsion and dysarthria (n = 6). In five patients
      with a coexisting infarct(s) in the brainstem, limb weakness and/or mental change
      were prominent and often masked the signs of cerebellar dysfunction. Six patients
      showed no stenosis or occlusion in the vertebrobasilar system on brain MRA. Five
      had an obvious cardiac source of emboli. Eight patients showed favorable outcomes
      with complete recovery or minimal disability, but three patients with additional
      extensive brainstem infarcts died within 1 week. CONCLUSIONS: Bilateral SCA
      territory infarcts show variable clinical, vascular topographic, and prognostic
      features. They usually result from cardiac emboli.

PMID- 16566946
TI  - Effect of sinomenine on gene expression of the IL-1 beta-activated human synovial
      sarcoma.
AB  - Sinomenine is an alkaloid with pharmacological effects of anti-inflammation, anti
      angiogenesis, anti-arthritis and immunosuppression. This study aimed to
      investigate the effect of sinomenine on gene expression of human synovial sarcoma
      cells (Hs701.T) activated by IL-1 beta. The proliferative effect of sinomenine
      was examined in the presence or absence of IL-1 beta by the [3H]-thymidine
      incorporation and MTT assay, respectively. Using DNA microarray technology and RT
      PCR, the activating action of IL-1 beta and modulatory effect of sinomenine on
      Hs701.T were simultaneously determined. Results showed that IL-1 beta could
      stimulate the proliferation and gene expression of Hs701.T cells. Sinomenine
      could significantly inhibit proliferation of IL-1 beta-activated Hs701.T cells
      and suppress expression of 17 genes including IL-6, PlGF, Daxx, and HSP27. These
      genes were found to be important in tumor progression through the mediation of
      inflammation, cell adhesion, proliferation, apoptosis and angiogenesis. In
      conclusion, our study provides supplementary information for the further studies
      on the pharmacological effects of sinomenine acting on synovial sarcoma.

PMID- 16566947
TI  - Difructose anhydride III and sodium caprate activate paracellular transport via
      different intracellular events in Caco-2 cells.
AB  - A nondigestible disaccharide, difructose anhydride (DFA) III, is known to
      activate calcium transport via tight junctions (TJs); however, the
      characteristics of and mechanisms for the increase in paracellular transport
      induced by DFAIII have not been clarified. We compared the effect of DFAIII with
      that of sodium caprate (C10), a well-known enhancer of TJ permeability, on the
      changes in TJ proteins, transport of paracellular markers, and effects of nine
      cellular signaling blockers using Caco-2 monolayers. The addition of DFAIII (0
      100mmol/L) and C10 (0-10mmol/L) to the apical medium of the Caco-2 monolayers
      dose-dependently decreased transepithelial electrical resistance (TER), which is
      an indicator of TJ permeability. The reduction with C10 was much faster than that
      with DFAIII. Transport of the paracellular markers of various molecular weights
      (182-43,200) was elevated by the addition of 100mmol/L DFAIII and 10mmol/L C10.
      The transport rates were much in the presence of C10 than of DFAIII, while the
      reduction in TER by two treatments was similar (from 1000 to 300Omega cm(2)).
      Treatment with DFAIII and C10 changed the distribution of actin filament and
      claudin-1, but not occludin, junctional adhesion molecule-1, or zonula occludens
      1; however, alterations in the patterns of the TJ proteins differed according to
      treatment. An inhibitor of myosin light chain kinase and a chelator of
      intracellular calcium ion ([Ca(2+)](i)) attenuated the TER reduction by C10, but
      not by DFAIII. These data demonstrate that the increase in TJ permeability
      induced by DFAIII results from the alterations to actin and claudin-1 via
      [Ca(2+)](i)-independent mechanisms.

PMID- 16566948
TI  - Acteoside and its aglycones protect primary cultures of rat cortical cells from
      glutamate-induced excitotoxicity.
AB  - We have previously reported that acteoside isolated from the leaves of Callicarpa
      dichotoma has significant neuroprotective activity against glutamate-induced
      neurotoxicity in primary cultured rat cortical cells. To determine the essential
      structural moiety within this phenylethanoid glycoside needed to exert
      neuroprotective activity, acteoside was hydrolyzed with acid into its aglycones,
      caffeic acid and 3',4'-dihydroxylphenylethanol. Caffeic acid and 3',4'
      dihydroxylphenylethanol also showed significant neuroprotective activities.
      Acteoside and its aglycones inhibited glutamate-induced intracellular Ca2+ influx
      resulting in overproduction of nitric oxide and reduced the formation of reactive
      oxygen species. These compounds preserved the mitochondrial membrane potential
      and the activities of antioxidative enzymes, such as superoxide dismutase,
      glutathione reductase and glutathione peroxidase reduced by glutamate. It was
      followed by the preservation of the level of glutathione and finally the
      inhibition of membrane lipid peroxidation.

PMID- 16566949
TI  - The 'amygdala theory of autism' revisited: linking structure to behavior.
AB  - The 'amygdala theory of autism' suggests a crucial role for the amygdala in the
      neurobiological basis of autism spectrum disorders. However, to date evidence is
      lacking of a direct relationship between amygdala measures and behavioral
      manifestations of autism in affected individuals. In 17 adult individuals with
      Asperger syndrome (AS) and 17 well-matched controls we therefore assessed
      associations between MRI-derived amygdala volume and behavioral variables of
      emotion recognition and social cognition, as well as with core AS symptomatology.
      Results revealed that individuals with AS exhibited impairments in emotion
      recognition and social cognition compared to controls and also showed atypical
      relationships between amygdala volumes and overall head size. We found positive
      associations between emotional and social understanding and amygdala volume in
      the control group, but not in the AS group. In the AS group however, amygdala
      size was negatively related to diagnostic parameters, with smaller amygdala
      volumes involving higher levels of restricted-repetitive behavior domains. Our
      data seem to indicate that in AS the amygdala is not crucially involved in social
      and emotional understanding. It may, however, be a mediator for narrow interest
      patterns and the imposition of routines and rituals. Our data, in conjunction
      with current literature, seem to argue for a modification of the 'amygdala theory
      of autism'.

PMID- 16566950
TI  - Independent associations between weight status and disability in adults: results
      from the Health Survey for England.
AB  - OBJECTIVES: While direct links between obesity and some illnesses are well
      established, there is a relative paucity of research on associations between
      obesity and disabilities. The aim of this study was to test for significant
      associations between overweight and obesity and the presence of a wide range of
      disabling conditions in adults, controlling for sex, age, education, social
      class, income, cigarette smoking status and alcohol consumption. STUDY DESIGN:
      Data were extracted from the Health Survey for England (2001); a cross-sectional
      survey of the community-dwelling population. In total, 8613 adult participants
      were included in the analysis. METHODS: Multivariate logistic regression was
      employed to test whether the odds of having a range of disabling conditions are
      higher in the overweight and obese populations compared with those in the ideal
      weight range. RESULTS: The risk of nearly all disabling conditions tested was
      elevated in the obese and morbidly obese groups. Of great importance for public
      health, the risks of musculoskeletal illness, arthritis and rheumatism, and
      personal care disability were significantly elevated, even in those in the
      overweight category (currently about half of the adult population living in the
      UK). CONCLUSIONS: Obesity is independently associated with a range of disabling
      conditions in adults. The present study highlights the need for further research
      into the mechanisms by which these associations occur.

PMID- 16566951
TI  - The impact of home safety promotion on different social strata in a WHO safe
      community.
AB  - OBJECTIVES: Few studies have investigated the impact of home safety promotion
      programmes on different social strata. The aim of this study was to investigate
      the distribution of effects of a community-based home safety programme on home
      injury rates among families with different connections to the labour market.
      METHODS: A quasi-experimental design was used, with pre- and post-implementation
      registrations covering the total populations below 65 years of age in the
      programme implementation area (population 41,000) and in a neighbouring
      comparison municipality (population 26,000) in Ostergotland County, Sweden.
      RESULTS: In the intervention and comparison areas, households in which the adults
      were not vocationally active displayed the highest rates of home injury. After 6
      years of programme activity, the home injury rates for males and females in all
      social status categories displayed a decreasing trend in the intervention area.
      The opposite was true for the comparison area, i.e. the incidence of injury
      increased, with the exception of females in non-vocationally active households.
      The decline in injury rates in the intervention area was statistically
      significant for males and females in the employed category and for males in the
      non-vocationally active category. Changes in injury rates in the comparison area
      were not statistically significant. CONCLUSION: The programme was partially
      successful in that it reduced the injury rate in non-vocationally active
      households, but it did not influence the injury rate in the employed households.
      The study design did not allow for conclusions regarding why the post
      intervention injury rates remained higher in non-vocationally active households.
      Further research on the association between the incidence of home injury and
      socio-economic factors is warranted.

PMID- 16566952
TI  - The history of qing hao in the Chinese materia medica.
AB  - Artemisinin is currently used for treating drug-resistant malaria. It is found in
      Artemisia annua and also in A. apiacea and A. lancea. Artemisia annua and A.
      apiacea were known to the Chinese in antiquity and, since they were easily
      confused with each other, both provided plant material for the herbal drug qing
      hao (blue-green hao). This article shows, however, that since at least the
      eleventh century Chinese scholars recognized the difference between the two
      species, and advocated the use of A. apiacea, rather than A. annua for 'treating
      lingering heat in joints and bones' and 'exhaustion due to heat/fevers'. The
      article furthermore provides a literal translation of the method of preparing
      qing hao for treating intermittent fever episodes, as advocated by the eminent
      physician Ge Hong in the fourth century CE. His recommendation was to soak the
      fresh plant in cold water, wring it out and ingest the expressed juice in its raw
      state. Both findings may have important practical implications for current
      traditional usage of the plant as an antimalarial: rather than using the dried
      leaves of A. annua in warm infusions, it suggests that fresh juice extraction
      from A. apiacea may improve efficacy.

PMID- 16566953
TI  - A versatile synthesis of 17-heteroaryl androstenes via palladium-mediated Suzuki
      cross-coupling with heteroaryl boronic acids.
AB  - Suzuki coupling of 17-iodoandrosta-5,16-dien-3beta-ol (1) and 17-iodoandrosta
      4,16-dien-3-one (2) with nine heteroaryl boronic acids (mainly 2- or 3-furanyl,
      thienyl, benzofuranyl and benzothienyl boronic acid derivatives) were carried out
      under normal Suzuki condition (Pd(PPh(3))(4), 2M Na(2)CO(3) and MeOH), generally
      yielded C(17)-heteroaryl steroids in moderate (10-60%) yields, but furanyl-2- and
      5-chlorothienyl-2-boronic acid did not give any coupling product.

PMID- 16566955
TI  - In silico studies using Radial Distribution Function approach for predicting
      affinity of 1 alpha,25-dihydroxyvitamin D(3) analogues for Vitamin D receptor.
AB  - The Radial Distribution Function (RDF) approach has been applied to the study of
      the chick intestinal VDR affinity of 49 Vitamin D analogues. A model able to
      describe more than 77.5% of the variance in the experimental activity was
      developed with the use of the mentioned approach. In contrast, none of four
      different approaches, including the use of Topological, BCUT, Randic molecular
      profiles and Geometrical descriptors were able to explain more than 55% of the
      variance in the mentioned property, with the same number of variables in the
      equation.

PMID- 16566954
TI  - Factors associated with estrogen receptors-alpha (ER-alpha) and -beta (ER-beta)
      and progesterone receptor abundance in obese and non obese pre- and post
      menopausal women.
AB  - There is scarce information about the factors associated with estrogen receptors
      (ER) at menopause. In 113 volunteers pre- and post-menopausal healthy women,
      grouped as with and without obesity, estrogen receptors-alpha and -beta, and
      progesterone receptor (PR) were measured by immunohistochemistry in skin punch
      biopsies obtained from the external gluteal area. In pre-menopausal women,
      biopsies and a blood sample were performed between days 7 and 14 of the cycle.
      Serum hormone levels were measured by immunoradiometric assay or
      radioimmunoassay. After menopause, ER and PR amounts decreased significantly. At
      pre-menopause, obese women had lower PR levels than non obese (P<.006). In the
      post-menopausal group, obese women showed higher ER-alpha (P<.03) and ER-beta
      (P<.02) levels than the non obese group. In the analysis of factors associated
      with the amount of steroid receptors for the total group, log[ER-alpha], log[ER
      beta], and log[PR] were associated with age (P<.002, <.005, and <.004,
      respectively). The log[ER-alpha] was also associated with log[FSH] (P<.0008);
      meanwhile, the log[PR] showed a marginal correlation with log[FSH]. In pre
      menopausal women no factor associated with any of the three receptors was found.
      In post-menopausal women log[ER-alpha] was associated with log[estrone] and
      log[DHEAS] (P<.003 and <.02, respectively). log[PR] was associated with BMI
      (P<.002), years since menopause (P<.05), and log[DHEAS] (P<.003). We concluded
      that ER and PR diminish sharply at post-menopause. At this stage the amount of
      receptors depends on several factors such as BMI, years since menopause, and
      androgen precursors.

PMID- 16566956
TI  - Absence of neurotoxic effects in leopard sharks, Triakis semifasciata, following
      domoic acid exposure.
AB  - Domoic acid (DA), a potent neurotoxin produced by select species of algae and
      diatoms, kills neurons bearing kainic acid-type glutamate receptors. Studies have
      shown that DA bioaccumulates in invertebrates and fish that consume the diatoms.
      In every vertebrate species tested or observed in the wild, dietary or systemic
      DA causes neuronal damage or clinical signs of neurotoxicity. Sharks, like marine
      birds and mammals, are exposed to DA through their diet; however, no research has
      demonstrated the effect of DA on shark behavior or physiology. In this study,
      juvenile leopard sharks (Triakis semifasciata) were given DA by intracoelomic
      injection at doses of 0, 1, 3, 9, and 27 mg/kg and observed for 7 days. The
      sharks failed to demonstrate behavioral or histological changes in response to
      the toxin. We identified putative brain glutamate receptors by probing western
      blots with an antibody specific for kainic acid-type glutamate receptors and
      demonstrated receptor localization in the cerebellum with immunohistochemistry.
      Blood levels of DA in three sharks dosed at 9 mg/kg fell rapidly within 1.5h of
      injection. We show that leopard sharks possess the molecular target for DA but
      are resistant to doses of DA known to be toxic to other vertebrates.

PMID- 16566957
TI  - Effect of soluble microbial products on microbial metabolisms related to nutrient
      removal.
AB  - In this study, the effect of soluble microbial products (SMP) on the metabolisms
      related to phosphate or nitrogen removal of activated sludge was investigated.
      Two anaerobic-aerobic activated sludge processes were operated, one with a
      hydraulic retention time (HRT) of 48 h (RunL) and the other 6.4 h (RunS). The
      longer HRT of RunL was intended to promote the accumulation of SMPs in the
      supernatant. With the sludge from RunS and the supernatant from both of the runs,
      supernatant exchange batch experiments (SEBEs) were conducted, in which the
      acetate uptake rate and phosphate release rates under anaerobic conditions and
      the phosphate uptake rate under aerobic conditions were measured as these
      metabolisms are related to enhanced biological phosphorus removal. The
      nitrification rate was also measured. The statistical analyses of the results
      from the SEBEs showed that the supernatant from RunL had an inhibitory effect on
      the anaerobic acetate uptake and nitrification of the sludge from RunS. The cause
      of which was attributed to SMPs in the supernatant from RunL. As a result, the
      inhibitory effect of SMPs on nitrification and anaerobic acetate uptake was
      confirmed.

PMID- 16566958
TI  - Biodegradability assessment of several priority hazardous substances: choice,
      application and relevance regarding toxicity and bacterial activity.
AB  - Nineteen compounds listed in the category of priority substances (PS) were
      selected for a biodegradation study using standardized tests. The compounds
      consist of pesticides, chlorinated solvents and volatile organic compounds
      (VOCs). In this paper, the choice of the most suitable method is discussed in
      relation to the physico-chemical properties of each substance. Zahn-Wellens,
      manometric respirometry and closed-bottle tests are alternatively used.
      Experimental results are presented and interpreted. Toxicity (Microtox) and
      bacterial viability (Bac-light) are also used as tools to investigate the
      influence of each substance on the microbial population (activated sludge). In
      addition, experimental values are compared with predictive data calculated
      according to quantitative structure activity relationships (QSARs) models. Biodeg
      Models were permitted to correctly estimate 17 substances; Survey Models and
      screening tests also revealed the same behavior for 16 target compounds.

PMID- 16566959
TI  - Highly potent anti-human GPVI monoclonal antibodies derived from GPVI knockout
      mouse immunization.
AB  - Recent progress in the understanding of thrombus formation has suggested an
      important role for glycoprotein (GP) VI in this process. To clarify the exact
      role in detail, it is necessary to use specific, high affinity inhibitory
      antibodies. However, possibly due to the conserved structure of GPVI among
      species, it has been difficult to obtain potent antibodies. In this study, we
      developed highly potent anti-human GPVI monoclonal antibodies using GPVI knockout
      mice for immunization. Fab fragments of these antibodies, named OM1 and OM2,
      potently inhibit collagen-induced platelet aggregation. The IC(50) values for OM1
      and OM2 are 0.6+/-0.05 and 1.7+/-0.5 microg/mL, respectively, showing potency
      greater than, or equal to that of abciximab (1.7+/-0.3 microg/mL), an anti
      GPIIb/IIIa antibody. Fab fragments of OM1 and OM2 also potently inhibit collagen
      induced ATP release, thromboxane A(2) formation, and platelet adhesion to
      immobilized collagen under static and flow conditions. Interestingly, platelet
      aggregation induced with collagen-related peptide was potently inhibited by OM2
      but not OM1, indicating that OM1 recognizes an epitope that is different from
      collagen-related peptide-binding site on GPVI. These results suggest that OM1 and
      OM2 may be useful tools to understand the role of GPVI in thrombus formation.
      Furthermore, these antibodies have the potential to be developed as a new class
      of therapeutic tool.

PMID- 16566961
TI  - Vitamin D: its role in cancer prevention and treatment.
AB  - Vitamin D, the sunshine vitamin, has been recognized for almost 100 years as
      being essential for bone health. Vitamin D provides an adequate amount of calcium
      and phosphorus for the normal development and mineralization of a healthy
      skeleton. Vitamin D made in the skin or ingested in the diet, however, is
      biologically inactive and requires obligate hydroxylations first in the liver to
      25-hydroxyvitamin D, and then in the kidney to 1,25-dihydroxyvitamin D. 25
      Hydroxyvitamin D is the major circulating form of vitamin D that is the best
      indicator of vitamin D status. 1,25-dihydroxyvitamin D is the biologically active
      form of vitamin D. This lipid-soluble hormone interacts with its specific nuclear
      receptor in the intestine and bone to regulate calcium metabolism. It is now
      recognized that the vitamin D receptor is also present in most tissues and cells
      in the body. 1,25-dihydroxyvitamin D, by interacting with its receptor in non
      calcemic tissues, is able to elicit a wide variety of biologic responses. 1,25
      dihydroxyvitamin D regulates cellular growth and influences the modulation of the
      immune system. There is compelling epidemiologic observations that suggest that
      living at higher latitudes is associated with increased risk of many common
      deadly cancers. Both prospective and retrospective studies help support the
      concept that it is vitamin D deficiency that is the driving force for increased
      risk of common cancers in people living at higher latitudes. Most tissues and
      cells not only have a vitamin D receptor, but also have the ability to make 1,25
      dihydroxyvitamin D. It has been suggested that increasing vitamin D intake or sun
      exposure increases circulating concentrations of 25-hydroxyvitamin D, which in
      turn, is metabolized to 1,25-dihydroxyvitamin D(3) in prostate, colon, breast,
      etc. The local cellular production of 1,25-dihydroxyvitamin D acts in an
      autocrine fashion to regulate cell growth and decrease the risk of the cells
      becoming malignant. Therefore, measurement of 25-hydroxyvitamin D is important
      not only to monitor vitamin D status for bone health, but also for cancer
      prevention.

PMID- 16566960
TI  - The role of ATP sensitive K+ channels and of nitric oxide synthase on myocardial
      ischemia/reperfusion-induced apoptosis.
AB  - During ischemia, ATP-sensitive K+ channels (KATP channels) open, and this
      triggers necrotic processes and apoptosis. In this study, we investigated whether
      selective sarcoplasmic and mitochondrial KATP channel blockers affected
      myocardial apoptosis and nitric oxide synthase (NOS) activity in a rat model of
      myocardial ischemia/reperfusion in vitro. Isolated rat hearts were subjected to
      30 min of coronary artery occlusion followed by 30 min of reperfusion. A
      selective sarcKATP channel blocker, HMR1098 and a selective mitoKATP channel
      blocker, 5-hydroxydecanoate, were added to the perfusion fluid 10 min before
      occlusion. Myocardial apoptosis was detected immunohistochemically using the
      TUNEL method. Myocardial inducible NOS (iNOS) and endothelial NOS (eNOS) were
      determined immunohistochemically. In control hearts, apoptosis induction was
      associated with a greater immunoreactivity of iNOS than eNOS. Treatment with
      HMR1098, at a concentration of 3 micromol/l, significantly reduced the TUNEL
      positive cardiomyocytes and this was associated with decreased iNOS and increased
      eNOS immunoreactivity. When this drug was administered at a higher concentration,
      at 30 micromol/l, a more marked reduction in apoptosis was observed but, in
      contrast to the effects observed at the lower drug concentration, eNOS
      immunoreactivity was almost completely abolished while iNOS was strong. Moreover,
      ischemia-induced cardiac dysfunction (e.g. contractile force and recovery of
      coronary flow) was increased by the higher concentration of HMR 1098. In hearts
      treated with 5-hydroxydecanoate, myocyte apoptosis was slightly reduced, and this
      was associated with an almost equal increase in both iNOS and eNOS
      immunoreactivity. These findings suggest that iNOS appears to be more important
      than eNOS in the reduction of apoptosis. However, the further inhibition of
      apoptosis by the higher concentration of HMR 1098 was associated with poorer
      cardiac function.

PMID- 16566962
TI  - Mesonephroid adenocarcinoma arising from mesonephroid metaplasia of the urinary
      bladder.
AB  - We present a rare case of mesonephroid adenocarcinoma arising from mesonephroid
      metaplasia of the urinary bladder. For the first time, the unique histopathologic
      features in this patient provide evidence for the theory that vesical
      mesonephroid adenocarcinoma might be a highly aggressive metaplastic variant of
      urothelial carcinoma that should be treated accordingly.

PMID- 16566964
TI  - Laparoscopic nephroureterectomy for transitional cell carcinoma of renal pelvis
      and ureter: Nagoya experience.
AB  - OBJECTIVES: To evaluate the efficacy of retroperitoneoscopic nephroureterectomy
      for transitional cell carcinoma of the renal pelvis and ureter, we analyzed the
      clinical outcomes and long-term cancer control of 89 patients. METHODS: In 36
      patients, the kidney was retroperitoneoscopically dissected and the ureteral end
      was resected with open procedure (combined laparoscopy group). In 53 patients,
      the ureteral end with a bladder cuff was transected using an endoscopic stapler
      (pure laparoscopy group). Sixty patients underwent open nephroureterectomy (open
      group). The median follow-up period was 35, 31, and 17 months in the open,
      combined, and pure laparoscopy groups, respectively. RESULTS: The average
      operative time and bleeding volume was 5.4 hours and 665 mL in the open group,
      5.1 hours and 580 mL in the combined laparoscopy group, and 4.3 hours and 354 mL
      in the pure laparoscopy group, respectively. The cause-specific patient survival
      rate at 3 years was 81% in the open group, 86% in the combined laparoscopy group,
      and 80% in the pure laparoscopy group. The bladder recurrence-free rate at 3
      years was 51% in the open group, 65% in the combined laparoscopy group, and 45%
      in the pure laparoscopy group. The extravesical recurrence-free rate at 3 years
      was 71% in the open surgery group, 76% in the combined laparoscopy group, and 71%
      in the pure laparoscopy group. No statistically significant difference was seen
      in patient survival, bladder recurrence, or extravesical recurrence rates among
      the three groups. CONCLUSIONS: Our retroperitoneal laparoscopic
      nephroureterectomy is less invasive than open surgery and is a safe and effective
      alternative.

PMID- 16566965
TI  - Chlorhexidine in urethral gel: does it cause pain at flexible cystoscopy?
AB  - OBJECTIVES: To investigate the effect of chlorhexidine gluconate in urethral
      local anesthetic gel on patients undergoing outpatient flexible cystoscopy. We
      postulated that chlorhexidine was contributing to the pain and urgency that
      occurs during and after cystoscopy. METHODS: A prospective randomized single
      blinded study was conducted. A total of 141 patients undergoing outpatient
      flexible cystoscopy participated in the study. They were randomized to receive 10
      mL of 2% lignocaine gel with 0.05% chlorhexidine gluconate (group 1, n = 72) or
      10 mL of 2% lignocaine and aqueous gel mixture (group 2, n = 69). Pain scores
      were recorded on a numerical visual analog scale from 0 to 10. RESULTS: The
      groups were well matched for the purposes of comparison. The mean pain scores
      were not significantly different between groups 1 and 2 at the insertion of the
      scope (2.1 versus 2.2, P = 0.7), during cystoscopy (1.8 versus 1.9, P = 0.759),
      and immediately after cystoscopy (1.4 versus 0.8, P = 0.06). However, a
      significant difference was found in the mean pain scores between groups 1 and 2
      during the first void (1.8 versus 1.0, P = 0.031) and after the first void (2.4
      versus 1.2, P = 0.007). A significant increase occurred in the reported levels of
      urgency after cystoscopy in group 1 (P = 0.018). No difference was found in the
      level of culture-proven symptomatic infection. CONCLUSIONS: Chlorhexidine appears
      to contribute to significant levels of pain and urgency after outpatient flexible
      cystoscopy.

PMID- 16566966
TI  - Impact of nocturia on symptom-specific quality of life among community-dwelling
      adults aged 40 years and older.
AB  - OBJECTIVES: To evaluate factors predicting the effect of nocturia in a community
      based cohort of adults using a nocturia-specific quality-of-life (N-QOL)
      questionnaire. METHODS: From October 2004 to February 2005, adults aged 40 years
      old or older living in Matsu, Taiwan and reporting nocturia of one episode or
      more per night were interviewed with a 12-item N-QOL questionnaire consisting of
      Sleep/Energy and Bother/Concern subscales. Univariate analyses were used to
      analyze the effects of demographic characteristics, frequency and duration of
      nocturia, and sleeping characteristics on the N-QOL score. Multiple linear
      regression analysis was used to identify factors predicting the N-QOL score.
      RESULTS: A total of 663 adults completed this study (mean age 59.4 years). The
      average N-QOL scores (a lower score indicates worse QOL) were 91.4 +/- 11.2, 83.7
      +/- 13.2, 77.6 +/- 16.8, and 67.6 +/- 21.2 for nocturia episodes of 1, 2, 3, and
      4 or more per night, respectively (P < 0.001). Men reported significantly lower N
      QOL (85.6 +/- 15.1 versus 88.9 +/- 13.1, P = 0.003) and Bother/Concern subscale
      scores (42.0 +/- 8.4 versus 44.0 +/- 7.4, P < 0.001), but not Energy/Sleep
      subscale scores (43.6 +/- 7.8 versus 44.4 +/- 7.3, P = 0.158) than women. On
      multiple linear regression analysis, increasing nocturia episodes (regression
      coefficient -6.2, 95% confidence interval -7.4 to -5.0), male sex (regression
      coefficient -3.5, 95% confidence interval -5.4 to -1.5), and degree of sleeping
      disturbance after nocturia (regression coefficient -4.5, 95% confidence interval 
      5.6 to -3.4) independently predicted a significantly lower N-QOL score.
      CONCLUSIONS: The results of our study have confirmed that nocturia has a more
      significant QOL impact when the patient has two or more episodes per night.
      Moreover, men experienced a greater impact from nocturia than women, particularly
      in the Bother/Concern domain.

PMID- 16566967
TI  - An implantable ligation device that achieves male sterilization without cutting
      the vas deferens.
AB  - OBJECTIVES: To determine whether the Vasclip implant procedure would (a) be
      equivalent to vasectomy in producing azoospermia, (b) produce greater patient
      satisfaction postoperatively, and (c) result in lower complication rates,
      postoperative pain, hematoma formation, spermatic granuloma, and surgical site
      infection when compared with historical controls. METHODS: Sterilization and
      complications were studied in 124 consecutive patients. RESULTS: Successful
      sterilization, defined by azoospermia at 10 to 14 months, was observed in 116 of
      119 subjects. The effectiveness seemed to be equivalent to that of vasectomy. The
      incidence of postoperative pain and hematoma formation was similar to that with
      standard methods. The Vasclip procedure had similar infection rates and seemed to
      have lower rates of sperm granuloma when compared with vasectomy. In 3 subjects
      with persistent presence of sperm, histologic examination after traditional
      vasectomy indicated that misalignment of the device led to partial vas incision
      with recanalization. Patient acceptability was high: of the clinical study
      patients, 99% of survey respondents would recommend that other men considering a
      vasectomy have the Vasclip procedure. CONCLUSIONS: The Vasclip implant procedure
      represents a new, effective, office-based alternative to vasectomy. Physicians'
      benefits can include reduced procedural time and reduction of postprocedural
      complications. Potential patients' benefits include reduced risk of postoperative
      infection and sperm granuloma formation.

PMID- 16566969
TI  - Bladder herniation through suprapubic incision for penile prosthesis.
AB  - To our knowledge, we present the first case of bladder herniation after insertion
      of an inflatable penile prosthesis. A 65-year-old man presented with a suprapubic
      bulge. He had his third inflatable penile prosthesis placed 1 year earlier. He
      had no voiding complaints but requested surgical intervention because the hernia
      was cosmetically undesirable. After the hernia sac was opened the majority of the
      bladder was found within it. The defect was repaired with Gore-Tex mesh and the
      reservoir replaced. One must consider bladder involvement in ventral hernias
      after penile prosthesis insertion, and a preoperative cystogram might assist in
      identifying hernia contents.

PMID- 16566968
TI  - Technical modification of microsurgical varicocelectomy can reduce operating
      time.
AB  - OBJECTIVES: To evaluate the impact of a technical modification of the
      microsurgical subinguinal varicocelectomy on surgical operating time. METHODS: We
      introduced a technical modification to the standard microsurgical subinguinal
      varicocelectomy (division of the spermatic cord package before microsurgical
      dissection) in January 1999, to simplify the procedure and reduce surgical
      operating time. We performed a retrospective review of surgical outcomes in 89
      men who underwent microsurgical varicocelectomy before modification of the
      procedure and 76 men who underwent microsurgical varicocelectomy after
      modification of the procedure. We compared operating times (in minutes),
      intraoperative findings, improvement in semen parameters, and postoperative
      complications between the two groups. RESULTS: Overall, 101 men underwent a left
      and 64 men bilateral microsurgical varicocelectomy. Operating time (mean +/-
      standard error of the mean) was significantly less for the modified procedure
      compared with standard microsurgical varicocelectomy (50.2 +/- 1.8 minutes versus
      56.5 +/- 1.3 minutes for left-sided procedures and 81.7 +/- 2.6 minutes versus
      104.0 +/- 4.0 minutes for bilateral procedures, respectively). No postoperative
      complications (including recurrence or clinical hydrocele) were identified at 6
      weeks postoperatively. Total motile sperm count improved significantly in both
      groups after surgery. CONCLUSIONS: The modified microsurgical varicocelectomy
      reduces surgical operating time significantly without compromising outcome.

PMID- 16566970
TI  - Hand port use for extraction during laparoscopic donor nephrectomy.
AB  - OBJECTIVES: To report our technique of laparoscopic donor nephrectomy using the
      hand port for specimen extraction. In 1999, our institution began a kidney
      transplant program. Donor nephrectomies have since been exclusively performed
      laparoscopically. Early in our experience, we used a specimen extraction bag to
      assist in graft removal, but encountered some complications. We subsequently
      changed our technique to include a hand port for specimen extraction. METHODS: A
      database of our experience was kept prospectively. The records of both donors and
      recipients were reviewed. We describe our technique of laparoscopic donor
      nephrectomy, including our new method of specimen extraction using a hand port.
      RESULTS: A total of 230 consecutive procedures were reviewed. We had excellent
      donor outcomes, including a mean operative time of 107.9 minutes and an estimated
      blood loss of 112.4 mL. In addition, the complication (12.6%) and open conversion
      (1.3%) rates were low. The time needed for specimen extraction decreased from
      3.16 minutes to 1.16 minutes (P <0.05) after implementation of the hand port.
      CONCLUSIONS: The hand port modification decreased the extraction time and allowed
      for a safer method of extraction. We believe that the hand port facilitates a
      procedure that contains a small margin of error.

PMID- 16566971
TI  - E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: analysis of
      125 patients.
AB  - OBJECTIVES: The treatment of choice for invasive penile carcinoma is amputation
      and lymphadenectomy. The latter is associated with a high morbidity rate.
      Analysis of new prognostic factors such as E-cadherin, matrix metalloproteinase
      (MMP)-2, and MMP-9 may help to select candidates for lymphadenectomy. METHODS: We
      assessed 125 patients with penile epidermoid carcinoma treated with amputation
      and bilateral lymphadenectomy. The following factors were analyzed: age, race,
      disease evolution time, venereal background, clinical and pathologic stage, tumor
      thickness, differentiation grade, venous and lymphatic embolization,
      koilocytosis, type of invasion, and E-cadherin, MMP-2, and MMP-9
      immunoreactivity. The value of risk factors for lymph node metastases and
      specific survival was assessed. RESULTS: The mean follow-up was 76.5 months.
      Clinical N stage (P = 0.001), tumor thickness (P = 0.027), lymphatic permeation
      (P < 0.001), venous embolization (P = 0.002), corpus cavernosum infiltration (P =
      0.002), and low E-cadherin expression (P = 0.032) significantly correlated with
      the presence of metastases. Independent risk factors for metastases were
      lymphatic permeation (relative risk [RR] = 5.99; 95% confidence interval [CI] 2.1
      to 16.9) and clinical N stage (RR = 5.5; 95% CI = 1.9 to 16.7). Lymph node
      metastases (RR = 57.9; 95% CI = 7.4 to 453.9), urethral infiltration (RR = 3.5;
      95% CI = 1.3 to 9.2), and MMP-9 immunoreactivity (RR = 3.2; 95% CI = 1.2 to 8.3)
      were considered independent risk factors for disease recurrence. CONCLUSIONS: On
      univariate analysis, low E-cadherin immunoreactivity was associated with a
      greater risk of lymph node metastases. High MMP-9 immunoreactivity was an
      independent risk factor for disease recurrence.

PMID- 16566972
TI  - Evaluation of prostatic massage in treatment of chronic prostatitis.
AB  - OBJECTIVES: To evaluate the efficacy of regular prostatic massage in combination
      with culture-specific antibiotic therapy for men with chronic prostatitis.
      METHODS: This study included 81 consecutive patients who attended our outpatient
      clinic with a history or symptoms suggestive of chronic prostatitis (National
      Institutes of Health category II and IIIA). In addition to prostatic culture and
      sensitivity, all patients were asked to complete the National Institutes of
      Health Chronic Prostatitis Symptom Index. According to their chronic prostatitis
      category, all patients were divided into four groups: group 1, chronic bacterial
      prostatitis treated with antibiotics and prostatic massage, n = 17; group 2,
      chronic bacterial prostatitis treated with antibiotics alone, n = 20; group 3,
      chronic nonbacterial prostatitis treated with antibiotics and prostatic massage,
      n = 25; and group 4, chronic nonbacterial prostatitis treated with antibiotics
      alone, n = 19. RESULTS: Of the 37 patients with initially positive cultures, 30
      (81.1%) had sterile final cultures. Overall, 30 patients (37%) of 81 had complete
      resolution of symptoms, 18 (22.2%) had initial resolution but had recurrence
      after therapy, 22 (27.1%) had partial improvement, and 11 (13.5%) had no
      improvement. No significant difference was found in the response between patients
      treated with antibiotics alone and those treated with antibiotics and prostatic
      massage in all four groups. Only 29% of class IIIa patients had complete
      improvement in contrast to 52% complete improvement in the class II patients.
      CONCLUSIONS: Prostatic massage did not significantly improve the response of
      patients with chronic pelvic pain syndrome to antibiotics. Patients with National
      Institutes of Health class II prostatitis should be primarily treated with
      culture-sensitive antibiotics. Treatment of nonbacterial prostatitis is
      challenging and requires additional extensive research.

PMID- 16566973
TI  - Pediatric kidney stones: long-term outcomes.
AB  - OBJECTIVES: To determine the specific risks for recurrent stone disease and which
      initial evaluations resulted in an effective reduction of risk, we undertook a
      long-term follow-up study of children who had experienced upper tract urinary
      stones. METHODS: Identified patients were contacted and interviewed using a
      structured questionnaire. The patient data were subcategorized and analyzed.
      RESULTS: The results demonstrated that our population had a recurrence rate
      similar to the reported adult stone recurrence rates. No evidence was found of
      impaired growth or development. Our population of noncircumcised boys did not
      demonstrate a high risk of struvite stones. Surgical techniques have evolved.
      Anatomic and metabolic factors were not a predictor of an adverse risk of
      recurrence. Cystinuria may carry extra risk, although our numbers were not
      sufficient to be sure. CONCLUSIONS: Extensive metabolic screening of children
      with upper tract urinary stones is not supported by the data from our patients.
      Testing for cystinuria is justified. The principles of screening and surveillance
      should match the recommended care of adults with stone formation.

PMID- 16566974
TI  - Contractile activity of the prostate at ejaculation: an electrophysiologic study.
AB  - OBJECTIVES: To investigate the hypothesis that the prostate contracts at
      ejaculation to push its secretions into the urethra. Although it has been
      mentioned that the prostate contracts at ejaculation, a report of this finding
      could not be traced in published studies. METHODS: The electromyographic activity
      of 8 canine prostates was recorded by applying an electrode to the prostate. The
      prostatic urethral pressure was simultaneously measured by means of a manometric
      catheter. The prostatic electromyographic and urethral pressures were recorded at
      rest and on ejaculation by penile electrovibration. RESULTS: The prostatic slow
      waves (SWs) and action potentials (APs), as well as the urethral pressure at
      rest, showed a significant increase during the ejaculatory bouts (P < 0.05 and P
      < 0.05, respectively). The SWs, APs, and pressure increase occurred
      simultaneously with each bout of ejaculatory spurt, which occurred at mean
      intervals of 1.1 +/- 0.02 seconds and a number of 4.6 +/- 1.2 bouts. CONCLUSIONS:
      The electric waves discharged from the prostate at rest seemed to produce
      prostatic contractions, which cause prostatic urethral pressure increases. At
      ejaculation, the intermittent increase of the wave variables and urethral
      pressure coincided with the ejaculatory spurts, apparently denoting intermittent
      prostatic smooth muscle contractions. These contractions seem to squeeze the
      prostatic secretions into the prostatic urethra.

PMID- 16566975
TI  - Neurovascular preservation in orthotopic cystectomy: impact on female sexual
      function.
AB  - OBJECTIVES: The published data regarding female orthotopic cystectomy have
      focused primarily on urethral recurrence and urinary continence. In a new era of
      sexuality, evaluating postoperative sexual outcome has become a new surgical
      endpoint. In this study, we focused on the impact of neurovascular preservation
      after radical cystectomy and neobladder construction. METHODS: We assessed female
      sexuality in 13 patients after orthotopic cystectomy using a standardized
      questionnaire, Female Sexual Function Index (FSFI). Six patients had undergone
      nerve-sparing cystectomy and seven had undergone contemporary non-nerve-sparing
      cystectomy. Intraoperatively, the tumor was deemed oncologically safe for
      neurovascular preservation. All 13 patients were sexually active preoperatively,
      were younger than 65 years old, had recurrence-free follow-up findings after 1
      year, and had undergone no pelvic irradiation. The 19-item FSFI questionnaire
      analyzed six domains (desire, arousal, lubrication, orgasm, satisfaction, and
      pain) of sexual function. RESULTS: In the nerve-sparing group (mean age 55.9
      years), the baseline and 12-month postoperative scores showed a minimal decline
      in results, with a total mean FSFI score of 24.5 versus 22.3, respectively. In
      analyzing each of the six domains, no significant decline or difference was
      observed. Conversely, in the non-nerve-sparing group (mean age 56.7 years), a
      significant decline or difference was found in the 12-month total mean FSFI
      scores between the baseline and postoperative FSFI scores (25.0 versus 11.0,
      respectively). In the non-nerve-sparing group, 6 of 7 patients ultimately
      discontinued sexual intercourse. CONCLUSIONS: Female sexual function was
      preserved in patients who received neurovascular preservation. In contrast, all
      domains of sexual function declined in patients who had undergone non
      neurovascular preservation.

PMID- 16566976
TI  - Sutureless nephron-sparing surgery: use of albumin glutaraldehyde tissue adhesive
      (BioGlue).
AB  - OBJECTIVES: To determine the feasibility of using serum albumin glutaraldehyde
      tissue adhesive (BioGlue) to achieve hemostasis and prevent urine leakage during
      nephron-sparing surgery (NSS). METHODS: From February 1993 to April 2005, 174 NSS
      operations were performed for renal cell carcinoma at our institute. A total of
      143 patients underwent NSS with the traditional suturing technique (suture group)
      and 31 patients underwent a sutureless BioGlue sealing-only procedure (BioGlue
      group). We compared the two groups for clinical and tumor characteristics and
      surgical outcome. RESULTS: The patient and tumor characteristics were similar in
      both groups. The average maximal tumor diameter was 4.21 cm (range 2.2 to 7) for
      the suture group and 3.67 cm (range 2 to 6.8) for the BioGlue group. The use of
      BioGlue reduced the mean warm ischemic time by 8.8 minutes (17.2 versus 26
      minutes, P = 0.002). The mean estimated blood loss was 45.1 mL in the BioGlue
      group and 111.7 mL in the suture group (P = 0.001). Blood transfusion was
      required in 1 patient (3.2%) of the BioGlue group and 24 (17%) in the suture
      group (P = 0.014). None of the patients treated with BioGlue developed urinary
      fistula compared with three (2%) in the suture group. CONCLUSIONS: Albumin
      glutaraldehyde tissue adhesive (BioGlue) alone provided adequate hemostasis
      during NSS, significantly decreasing the blood loss and transfusion rate, as well
      as the renal ischemic and operative times. BioGlue was easy to use and safe for
      sealing the kidney during partial nephrectomy. Future prospective clinical trials
      are necessary to validate its role during renal surgery.

PMID- 16566978
TI  - Association of PAX5 expression with clinical outcome in patients with TaT1
      transitional cell carcinoma of the bladder.
AB  - OBJECTIVES: To assess the frequency and intensity of PAX5 gene messenger
      ribonucleic acid (mRNA) expression in TaT1 bladder cancer tissue, as well as its
      correlation with clinicopathologic variables and patient outcome. METHODS: The
      RNA expression of PAX5 was evaluated with reverse transcriptase polymerase chain
      reaction in the tumor tissue of 75 patients with stage TaT1 bladder cancer
      treated with transurethral resection. Patients were observed with cystoscopy and
      urinary cytologic evaluation. The association between PAX5 expression and
      clinicopathologic variables and patient outcome was evaluated. Benign urothelium
      from 8 patients with benign prostatic hyperplasia was obtained. These patients
      were used as a control group. RESULTS: PAX5 expression was found in 62 patients
      with bladder cancer (82.7%) but in no patient from the control group. High PAX5
      expression (greater than 0.2) was confirmed in 19 patients (25.3%). No
      significant relationship was observed between quantity of PAX5 expression and
      clinicopathologic variables. The 3-year recurrence-free and progression-free
      survival rates in highly positive patients were 13.2% and 71.6%, compared with
      40.6% and 92.8%, respectively, in patients with weak or negative expression (log
      rank test, P = 0.0075, P = 0.022). Multivariate Cox proportional hazard model
      analysis identified PAX5 expression as an independent predictor of tumor
      recurrence. CONCLUSIONS: PAX5 gene expression is a frequent finding in
      superficial transitional cell carcinoma of the bladder. High levels of PAX5 are
      associated with poorer recurrence-free and progression-free survival rates.
      Moreover, PAX5 expression was found to be an independent prognostic factor for
      recurrence-free survival by a multivariate analysis.

PMID- 16566977
TI  - Comparative effects of in vitro ischemia on contractile responses of mouse and
      rat bladders to various forms of stimulation.
AB  - OBJECTIVES: To compare in an in vitro study the sensitivity of rat and mouse
      bladders to ischemia and reperfusion. Urinary bladder dysfunction is related to
      ischemia and reperfusion. Several studies have been conducted in which one animal
      model was used in the urinary bladder dysfunction experiments, but very few
      studies have compared the consequences of urinary bladder dysfunction in
      different species. METHODS: Male rats and mice were anesthetized and their
      bladders removed. Bladder strips were placed in 15-mL baths containing oxygenated
      Tyrode's solution with glucose. Strips were stimulated by field stimulation,
      carbachol, and KCl, and the responses were recorded. Individual strips were
      switched for 1 hour to Tyrode's with no glucose equilibrated with nitrogen.
      During this hour, one half of the strips received repetitive stimulation. After
      the 1 hour of ischemia, the strips were returned to Tyrode's solution with
      glucose and oxygen for 1 hour without repetitive stimulation. The strips were
      restimulated as described above. RESULTS: The rat bladder generated significantly
      greater tension than the mouse bladder. The responses of the mouse, but not the
      rat, bladder strips were suppressed after repetitive field stimulation in normal
      solution. In both species, the responses were suppressed under ischemic
      conditions with or without repetitive stimulation. The responses of the mouse
      bladders were more sensitive to ischemia and repetitive stimulation than rat
      bladders. CONCLUSIONS: These results have demonstrated that the mouse bladder is
      more sensitive to ischemic stress than the rat bladder. This information would be
      important when choosing species for the study of ischemia and reperfusion.

PMID- 16566979
TI  - Robotic-assisted laparoscopic prostatectomy in overweight and obese patients.
AB  - OBJECTIVES: To assess outcomes of robotic laparoscopic radical prostatectomy
      (RLRP) in overweight and obese patients, defined as those with a body mass index
      (BMI) of 25 to 30 kg/m2 and greater than 30 kg/m2, respectively. METHODS: This
      was a nonrandomized study evaluating all of our RLRP patients. Patients were
      divided into three groups: BMI of 25 kg/m2 or less (group 1), BMI greater than 25
      kg/m2 and less than 30 kg/m2 (group 2), and BMI of 30 kg/m2 or more (group 3).
      Patients were evaluated prospectively with the validated Rand 36-Item Health
      Survey (version 2) and with the University of California, Los Angeles Prostate
      Cancer Index questionnaire. RESULTS: Between February 2003 and November 2004, 150
      RLRPs were performed at our center. Average follow-up was 8 months. Groups 1, 2,
      and 3 had 39, 65, and 46 patients, respectively. Average BMIs for all three
      groups were statistically different (P < 0.01). When compared with group 1, open
      conversion rates, hospital stay, positive margin, and complication rates were not
      statistically different for groups 2 or 3. Operative time (P < 0.004) and
      estimated blood loss (P < 0.03), however, were statistically greater for group 3
      compared with group 1. Transfusion rate was highest in group 2 (P = 0.04 compared
      with group 1). Prostate weights were also statistically greater in groups 2 (P =
      0.003) and 3 (P = 0.02) compared with group 1. Overall, BMI did not increase
      perioperative and postoperative morbidity. CONCLUSIONS: Robotic laparoscopic
      radical prostatectomy is safe in overweight and obese patients and might be the
      surgical management of choice in this subset of patients. Further long-term
      follow-up with more patients is required to verify this initial observation.

PMID- 16566980
TI  - New biocompatible highly purified collagen gel for therapeutic renal artery
      embolization.
AB  - OBJECTIVES: To evaluate the effectiveness and safety of a new purified collagen
      gel with specific properties for renal artery embolization in an experimental
      model in dogs. METHODS: The new gel was prepared from type I bovine tendon
      collagen, highly purified to eliminate immunogenicity, and reconstituted through
      extensive dialysis in distilled water without the addition of glutaraldehyde. The
      study was conducted on 16 mongrel dogs that underwent random embolization of the
      renal artery. The dogs were divided into two groups: group 1 was killed after 2
      days and group 2 after 21 days. The abdominal organs, lungs, and muscles of the
      posterior limbs were studied in detail and samples were taken for an anatomic
      pathologic analysis. RESULTS: After embolization, uniform parenchymatosus
      ischemia and loose perirenal adhesions without significant volumetric changes
      were observed in group 1. A microscopic study revealed acidophilus amorphous and
      birefringent emboli filling the lumen of the renal artery and extending into the
      arterioles. The glomeruli and tubules showed early signs of diffused necrosis. In
      group 2, microscopic examination revealed endothelial proliferation around the
      emboli that had closely adhered to the arterial wall, with signs of fibroblastic
      proliferation within the emboli. In both groups, the abdominal organs, lungs, and
      muscles of the posterior limbs did not show signs of collagen migration.
      CONCLUSIONS: Purified collagen gel effectively embolized the renal artery. The
      absence of collagen migration to other organs and posterior limbs suggests that
      this material can be safely used for organ embolization.

PMID- 16566981
TI  - Prognostic implication of capsular invasion without perinephric fat infiltration
      in localized renal cell carcinoma.
AB  - OBJECTIVES: To analyze the prognostic value of capsular invasion without
      perinephric fat infiltration in patients with localized renal cell carcinoma
      (RCC) Stage pT1-pT2N0M0. METHODS: A total of 288 patients with RCC (conventional
      type) confined to the kidney (pT1-pT2N0M0) who underwent radical nephrectomy from
      January 1993 to November 2004 at our institution were included in our study. The
      disease of all patients was staged according to the 2002 TNM classification
      system. Pathologic findings, including T stage, nuclear grade, and capsular
      invasion, were retrospectively reviewed. Disease-specific survival was compared
      according to the capsular invasion. RESULTS: Tumor invasion of the renal capsule
      was identified in 108 (37.5%) of the 288 patients. Of the 230 patients with Stage
      pT1, 78 (33.9%) had lesions invading the renal capsule and 30 (51.7%) of 58
      patients with Stage pT2 had capsular invasion. Involvement of the renal capsule
      was associated with a worse pT stage (P = 0.015). The 5-year disease-specific
      survival rate for patients with no capsular invasion versus with capsular
      invasion was 91.8% versus 84.3%, respectively (P = 0.132). For patients with pT1
      tumors, the 5-year disease-specific survival rate was 95.6% for patients without
      capsular invasion and 92.6% for those with capsular invasion (P = 0.299). For
      patients with pT2 tumors, the 5-year disease-specific survival rate was 90.5% for
      patients without capsular invasion and 73.8% for those with capsular invasion (P
      = 0.031). CONCLUSIONS: Renal capsular invasion is associated with a worse stage
      in localized RCC. Patients with Stage pT2 RCC and capsular invasion appear to
      have a worse prognosis than those with equivalently staged RCC without capsular
      invasion.

PMID- 16566982
TI  - Ureteroscopic laser papillotomy to treat papillary calcifications associated with
      chronic flank pain.
AB  - OBJECTIVES: To evaluate retrospectively the efficacy and durability of a novel
      approach using ureteroscopic laser papillotomy for the treatment of painful
      papillary calcifications. Chronic pain due to renal papillary calcifications has
      not been addressed by current techniques. METHODS: Ureteroscopic holmium laser
      lithotripsy and papillotomy were performed on patients with chronic pain and
      radiographically visible papillary calcifications without free collecting system
      calculi. The papillary urothelium overlying all cystic dilations and intraductal
      calcifications was vaporized. Treated patients answered a telephone survey to
      assess pain scores, duration of response, use of narcotics, and patient
      satisfaction. We reviewed the medical records to evaluate for procedure-related
      complications and serum creatinine measurements. RESULTS: Of 20 patients who
      underwent laser papillotomy and responded to the telephone survey, 7 had
      bilateral procedures, yielding 27 renal units available for analysis. "Much less
      pain" was reported after 85% of the procedures, with a durable improvement
      reported after 59% of the procedures, at a median follow-up of 14.5 months.
      Significant improvements in the median pain scores were seen at 1 month (1.0, P
      <0.001), 6 months (2.0, P <0.001), and 1 year (1.5, P <0.001) compared with a
      median preoperative pain score of 9.0. The mean serum creatinine was unchanged
      after the procedure. CONCLUSIONS: Ureteroscopic laser papillotomy appears to be
      an effective treatment option for the chronic pain associated with papillary
      calcifications. Laser papillotomy offers hope to patients who would otherwise
      have been denied an attempt at treatment because of a lack of free calculi within
      the collecting system.

PMID- 16566983
TI  - Long-term outcome of abdominal sacrocolpopexy using xenograft compared with
      synthetic mesh.
AB  - OBJECTIVES: To assess the clinical outcome after abdominal sacrocolpopexy using a
      porcine dermal graft compared with a synthetic mesh. METHODS: Patients with
      vaginal vault prolapse Stage II or worse (Baden-Walker staging), underwent
      sacrocolpopexy using a synthetic mesh (n = 25) or porcine collagen graft (n =
      27). The subjective outcome was measured using validated questionnaires. RESULTS:
      The mean clinical follow-up from surgery was 7.1 months for the xenograft
      compared with 7.4 months for the synthetic cohort. At clinical follow-up, vaginal
      vault prolapse Stage II was present in 8 (29%) of 27 patients in the xenograft
      cohort and 6 (24%) of 25 patients in the synthetic mesh cohort (no significant
      difference). The mean follow-up from surgery to survey was 2.5 years in the
      xenograft cohort and 4.3 years in the synthetic cohort. None of the patients in
      either cohort had undergone a secondary sacrocolpopexy. No significant
      differences were found between the cohorts regarding surgical morbidity other
      than more patients experiencing fever for 1 to 3 days in the xenograft cohort (P
      < 0.001). No significant differences were found in lower urinary tract symptoms,
      anorectal symptoms, or quality-of-life variables between the two cohorts.
      CONCLUSIONS: Abdominal sacrocolpopexy using a porcine dermal graft was comparable
      to synthetic mesh in terms of subjective and anatomic outcomes at mid to long
      term follow-up.

PMID- 16566984
TI  - Urinary matrix metalloproteinase activity is not significantly altered in
      patients with renal cell carcinoma.
AB  - OBJECTIVES: Matrix metalloproteinases (MMPs) are proteins that degrade the
      extracellular matrix and have been shown to be elevated in the urine of patients
      with cancer. One action of MMPs is the degradation of collagen IV that plays a
      role in tumor invasion and metastasis. This degradation can be measured by a
      fluorescent microplate activity assay that has been suggested to identify
      patients with renal cell carcinoma (RCC). Our aim was to confirm the utility of
      urinary MMP activity as a diagnostic test for RCC. METHODS: Urine samples from 21
      patients undergoing nephrectomy for renal masses, as well as from 2 patients
      undergoing retroperitoneal mass excision for presumed local recurrence, were
      collected. Urine samples from 47 healthy volunteers were also collected. After
      concentration, the urine samples were incubated with fluorescein-labeled collagen
      IV. The fluorescence activity in each sample was measured using a conventional
      fluorescent microplate reader to determine the degree of collagen IV degradation
      in each specimen. RESULTS: Of the 21 patients undergoing nephrectomy, 15 had RCC,
      and both patients undergoing retroperitoneal mass excision had pathologically
      confirmed RCC recurrence. The mean number of fluorescence units emitted from the
      urine of patients with RCC was 48,924 units (range 0 to 275,879). The mean number
      of fluorescence units emitted from the urine of healthy patients was 29,834 units
      (range 0 to 400,086). This difference was not statistically significant (P =
      0.34). CONCLUSIONS: Despite previous evidence, urinary MMP activity was not an
      adequate test to identify RCC. Most normal urine samples had significant MMP
      activity.

PMID- 16566985
TI  - Androgen receptor immunostaining and androgen receptor messenger ribonucleic acid
      expression are increased in cremaster muscles associated with undescended testis.
AB  - OBJECTIVES: To determine and compare androgen receptor (AR) immunostaining and AR
      messenger ribonucleic acid (mRNA) expression in cremaster muscles associated with
      descended or undescended testis. METHODS: Eight boys with descended testis but
      with inguinal hernia and 8 boys with undescended testis were evaluated. Serum
      follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and
      free testosterone levels were determined, and samples of cremaster muscles were
      immunostained for AR. Groups were compared by unpaired t tests and Fisher's exact
      tests; P values of <0.05 were considered significant. Samples of cremaster
      muscles were obtained from another 5 boys with descended testis but with inguinal
      hernia and 5 boys with undescended testis. The expression of AR mRNA in those
      samples was determined by semiquantitative reverse transcriptase polymerase chain
      reaction. RESULTS: Serum FSH, LH, testosterone, and free testosterone levels were
      similar among groups. None of the samples from boys with descended testis showed
      positive staining, but 4 of 8 samples from boys with undescended testis stained
      positive for AR. Androgen receptor mRNA transcript levels were approximately 10
      times lower in cremaster muscles of boys with descended testis compared with
      those in boys with undescended testis. CONCLUSIONS: Despite similar serum hormone
      levels, more AR expression in cremaster muscles associated with undescended
      testis might represent evidence of being subjected to a lesser degree of
      androgenic effects.

PMID- 16566986
TI  - Testicular infarction in a 12-year-old boy with Wegener's granulomatosis.
AB  - We present the case of a 12-year-old boy with testicular infarction secondary to
      Wegener's granulomatosis. Scrotal exploration revealed no evidence of testicular
      torsion. The testis was left in place, and, after systemic therapy, partial
      reperfusion was present.

PMID- 16566987
TI  - Heterotopic ossification of percutaneous nephrostomy tract.
AB  - Heterotopic ossification is a rare, abnormal formation of true bone within
      extraskeletal soft tissues and is a common complication after musculoskeletal
      trauma or orthopedic procedures. We report a case of heterotopic ossification of
      a percutaneous nephrostomy tract causing flank pain and masquerading as a
      retained nephrostomy catheter in a young steroid-dependent man with sarcoidosis 2
      years after percutaneous nephrolithotomy. The patient's underlying sarcoidosis
      combined with local tissue ischemia likely contributed to this rare complication.

PMID- 16566988
TI  - Post-robotic prostatectomy urinary continence: characterization of perfect
      continence versus occasional dribbling in pad-free men.
AB  - OBJECTIVES: To review and characterize two groups of men who report being pad
      free after robot-assisted laparoscopic prostatectomy (RLRP): those with
      occasional incontinence and those with complete control. METHODS: The study
      included 106 out of a total of 195 men who underwent RLRP. Inclusion requirements
      were adequate follow-up and no-pad continence status. All patients completed self
      administered American Urological Association symptom score (AUAss) and continence
      questionnaires and underwent measurement of peak urinary flow rates, postvoid
      residual volumes, and voided volumes (VV) before and 3 months after surgery. All
      data and standard clinical characteristics were entered prospectively into an
      electronic database. RESULTS: Two distinct groups reported wearing no pads: the
      "perfect" group (n = 32) reported never leaking, and the "imperfect" group (n =
      74) reported occasional leakage but did not wear pads. Preoperatively, the
      "imperfect" group was older (62.2 versus 59 years) and had more urinary symptoms
      (all P < 0.05). Postoperatively, the "imperfect" group took longer to achieve a
      pad-free status (median 39.8 versus 19.3 days), had larger prostates (mean 50.9
      versus 43.2 g), had lower VV (324 versus 405 mL), and more urinary symptoms
      (AUAss 7.4 versus 4.3; all P < 0.05). CONCLUSIONS: Sixty-nine percent of men who
      attain "pad-free continence" after RLRP have occasional urinary leakage.
      Preoperatively, these men are characteristically older and have larger prostates,
      AUAss, and bother scores. Postoperatively, the "imperfect" group takes longer to
      achieve pad-free status and has smaller bladder capacities and more urinary
      symptoms. These results suggest that an overactive detrusor is the likely
      contributing etiology.

PMID- 16566989
TI  - Malignant teratoma 32 years after treatment of germ cell tumor confined to
      testis.
AB  - After the first 2 years of follow-up, the prognosis of testicular cancer confined
      to the testis is traditionally considered excellent. We report on a man who
      presented with a psoas mass, corresponding to a very late relapse of his left
      testicular cancer initially confined to the testis and confirmed by negative
      retroperitoneal lymph node dissection. Histologic analysis of the mass revealed
      malignant teratoma. The patient's history was remarkable because of the very long
      interval to relapse (32 years) associated with this malignant teratoma. This
      clinical case illustrates the possibility of late relapses throughout life,
      whatever the initial stage.

PMID- 16566990
TI  - Review pathology in a diagnostic bladder cancer trial: effect of patient risk
      category.
AB  - OBJECTIVES: Bladder cancer pathologic features are a continuous spectrum from
      benign to invasive lesions, causing diagnostic difficulties. Review pathology
      might be an answer, but appears to be of limited value. We studied the effect of
      patients' risk profile on the value of review pathology. METHODS: We used three
      Phase III multicenter studies that assessed the value of hexaminolevulinate
      fluorescence cystoscopy on diagnosis and management. Two studies (Europe and
      United States) included patients at high risk of carcinoma in situ (CIS), the
      third study (Europe) included all patients at risk of bladder cancer. Tumors and
      biopsies were examined by a local and review pathologist. RESULTS: The percentage
      of patients with CIS was high in the first two studies (20.6% and 15.9%) compared
      with the epidemiologic data (7.9%) and the third study (7.8%). The numbers of
      patients (specimens) in the three studies were 209 (927), 277 (986), and 142
      (553). Overall conformity for both grade and stage was between 50.5% and 56.6%,
      comparable to published data. Although conformity was best in the high-risk
      study, this was predominantly because of the better conformity in low-risk
      tumors. Conformity in Stage T1, CIS, and invasive tumors was low. The results
      from Europe and the United States were comparable, although the local pathologist
      in the United States tended to overstage or overgrade. CONCLUSIONS: Although
      histologic conformity was greater in the high-risk patient population, this was
      mainly a result of pTa tumors. The diagnosis of pT1, CIS, and invasiveness
      appears difficult. Because these tumors significantly influence therapy, review
      pathology in patients at high risk or suspicious for high risk should be
      considered.

PMID- 16566991
TI  - Implants of noninvasive papillary urothelial carcinoma in peritoneum and
      ileocolonic neobladder: support for "seed and soil" hypothesis of bladder
      recurrence.
AB  - OBJECTIVES: To explore the underlying mechanism of tumor regrowth in cases of
      noninvasive urothelial carcinoma that recur in unusual anatomic locations.
      METHODS: The pathology files of our institution and the consult service of one of
      us were searched for cases of noninvasive nonmetastatic urothelial carcinoma with
      involvement of unusual anatomic sites. Cases in which the mode of spread included
      direct spread to the adjacent tissue and lymphovascular metastases were excluded.
      Medical history, including presenting symptoms, and follow-up data were obtained.
      RESULTS: Two cases of noninvasive urothelial carcinoma were identified. One had
      presented as an implant in the peritoneal investment of the bladder dome and the
      other as multiple implants growing on the benign surface of the colonic mucosa of
      an orthotopic neobladder distant from the anastomosis site. Both cases had
      initially presented as noninvasive papillary urothelial carcinoma of the renal
      pelvis. Although the urinary bladder was free of neoplastic changes at
      nephroureterectomy, both patients also developed several papillary tumors within
      the bladder shortly after the removal of the kidney. CONCLUSIONS: After
      clinicopathologic correlation, the mode of tumor spread in these cases was best
      explained by the "seeding/implantation" theory. The urothelial tumor cells in
      each of these cases demonstrated the ability to implant themselves not only in
      the urothelium of the bladder but also in the colonic mucosa of a constructed
      neobladder and on the peritoneal surface.

PMID- 16566992
TI  - Pediatric blunt renal trauma: its conservative management and patterns of
      associated injuries.
AB  - OBJECTIVES: To review the conservative management of pediatric renal trauma and
      investigate the significance of associated nonrenal injuries. METHODS: We
      performed a retrospective review of 63 pediatric patients with blunt renal injury
      who were treated expectantly. A comparison was made between operative and
      nonoperative management, mechanism of injury, treatment complications,
      requirement for blood transfusion, length of hospital stay, associated injuries,
      and incidence of pre-existing urologic conditions. RESULTS: The renal injury
      grade was grade I in 31 patients, grade II in 12, grade III in 8, grade IV in 10,
      and grade V in 2. Two patients underwent acute surgical exploration; one for
      nonrenal causes and one (2%) for life-threatening renal bleeding (grade V
      injury). Renorrhaphy was not performed, and 98% of patients were initially
      treated nonoperatively. Three patients (5%) underwent delayed renal surgery: one
      nephrectomy for Wilms' tumor, one partial nephrectomy for nonhealing grade IV
      injury, and one attempted repair of a renal pelvis injury with subsequent
      nephrectomy. Excluding 1 patient who died and one nephrectomy for tumor control,
      our renal salvage rate was 97% (59 of 61). The overall mean hospital stay was 7.7
      days and was similar across all grades (grade I, 7.7 days; grade II, 7.8; grade
      III, 6.1; grade IV, 9.2; and grade V, 10.5 days). CONCLUSIONS: The results of our
      study have shown that pediatric patients with blunt nonexsanguinating renal
      injuries treated conservatively do well. The length of hospital stay did not
      increase with worsening severity of renal injury and, instead, was determined by
      the severity of the nonrenal associated injuries. This report adds to a growing
      body of published data that suggest that conservative management of pediatric
      blunt renal trauma is safe.

PMID- 16566993
TI  - Phase I/II dose finding study of combination cisplatin and gemcitabine in
      patients with recurrent cervix cancer.
AB  - OBJECTIVES: To evaluate the toxicity and efficacy of cisplatin and gemcitabine in
      women with recurrent cervical cancer. METHODS: A multi-institutional phase I/II
      dose finding study of cisplatin and gemcitabine delivered to women with recurrent
      previously radiated cervical carcinoma. RESULTS: Twenty eight patients were
      enrolled. The mean and median age of patients was 51 years (age range 35 to 70
      years). Chemotherapy was given on a 28-day cycle; cisplatin was administered at a
      fixed dose of 50 mg/m(2), day 1 and gemcitabine, days 1, 8, and 15. Gemcitabine
      doses started at 600 mg/m(2) (dose level 1) and were escalated by 100
      mg/m(2)/dose level until 1000 mg/m(2) (dose level 5). Twenty seven patients were
      evaluable for toxicity and disease response, and 75 cycles of chemotherapy were
      administered. Toxicities were predominantly hematological; 18% of patients
      experienced grade 3 anemia, 37% grade 3 and 11% grade 4 leukopenia, 41% grade 3
      neutropenia, and 26% grade 3 thrombocytopenia. The maximally tolerated dose (MTD)
      was not reached. One patient experienced a dose-limiting toxicity on dose level 2
      (febrile neutropenia). One patient had a CR and 3 patients had a PR to therapy
      (15% response rate), 41% of patients had SD, and 44% had progression of cancer.
      Median survival was 11.9 months. CONCLUSION: Although this 28-day gemcitabine and
      cisplatin regimen in recurrent cervix cancer has tolerable toxicity, 21-day
      regimens are recommended because of improved practicality, higher dose intensity,
      and higher response rates.

PMID- 16566994
TI  - Reproduction in high body condition mares with high versus low leptin
      concentrations.
AB  - Previous results from our laboratory indicated that a majority of mares with high
      body condition scores (BCS) displayed estrous cycles or had considerable
      follicular activity during the winter. Among these high BCS mares, about 35% of
      them exhibited a persistent hyperleptinemia and hyperinsulinemia. The current
      experiment was designed to compare the reproductive characteristics of high BCS
      mares with hyperleptinemia to those with normal (low) plasma concentrations of
      leptin during the winter and the first estrous cycle (or the first full cycle
      encountered for those already cycling). Light horse mares with high BCS (6-8.5)
      were assigned to groups based on leptin concentrations (8/group): low (<5 ng/mL)
      and high (>10 ng/mL). Beginning 7 January, mares were assessed every 3d for
      follicular activity and then daily once a follicle >25 mm was detected. Mares
      were subsequently monitored through their first and second ovulations. Leptin
      concentrations remained higher (P<0.001) in mares in the high leptin group over
      the duration of the experiment. Also, high leptin mares had greater (P<0.0001)
      insulin response to glucose infusion and a faster (P<0.05) rate of glucose
      clearance. One mare with high leptin and three mares with low leptin had
      progesterone concentrations indicative of the presence of a corpus luteum at the
      onset of the experiment. Plasma concentrations of LH, FSH, and progesterone did
      not differ between groups (P>0.1) during the first estrous cycle occurring after
      7 January. Date of first ovulation after 7 January and interovulatory interval
      were similar (P>0.1) for the two groups, as were estimates of follicular numbers
      on the ovaries (small, medium, and large; P>0.1). It is concluded that the
      perturbations in leptin and insulin secretion observed in some high BCS mares are
      not associated with alterations in ovarian activity or the estrous cycle during
      winter and into the period of vernal transition.

PMID- 16566995
TI  - Assessment of plasma profile of pregnancy-associated glycoprotein (PAG) in sheep
      with a heterologous (anti-caPAG55+59) RIA and its potential for diagnosing
      pregnancy.
AB  - The purpose of the present investigation was to generate pregnancy associated
      glycoprotein (PAG)-profiles throughout pregnancy in a heterogenous sample of
      sheep using a radioimmunoassay with a heterologous antibody (anti-caPAG(55+59),
      #708) and utilize them for the purpose of pregnancy detection. From 2 weeks after
      the introduction of males into the breeding herd until 4 weeks after parturition,
      weekly blood samples were collected from 66 pregnant and 25 non-pregnant ewes of
      various breeds. Between 3 and 5 weeks after conception, plasma PAG levels
      increased, remained almost stable until week 17, then continued to increase,
      culminating in a drastic surge during the last 2 weeks of pregnancy. By 4 weeks
      of gestation, the plasma PAG level exceeded the level typical for non-pregnant
      ewes by five standard deviations, permitting a reliable pregnancy diagnosis.
      Plasma PAG levels were higher in twin-bearing ewes than in ewes carrying a single
      lamb, differences getting more evident as pregnancy proceeded. Neither breed and
      parity of the mother nor sex and weight of lambs borne exerted a significant
      effect. The heterologous assay system utilizing a caprine antibody proved to
      deliver results that are more consistent and less depending on various variables
      than those used in other studies. It may be concluded that, at the present state
      of development, the assay provides a reliable means of diagnosing pregnancy in
      sheep from the 4th week after they have been bred onward.

PMID- 16566996
TI  - A response to Bernstein Ratner (2005). Evidence-based practice in stuttering:
      some questions to consider.

PMID- 16566997
TI  - Rheological characterization of composites using a vertical oscillation
      rheometer.
AB  - OBJECTIVES: The purpose of this study was to investigate the viscoelastic
      properties related to the handling characteristics of composites. METHODS: A
      custom-designed vertical oscillation rheometer (VOR) was used for the rheological
      measurements of composites. The VOR consists of three parts: (1) a measuring
      unit, (2) a deformation induction unit, and (3) a force-detecting unit. Two
      medium-viscous composites, Z100 and Z250, and two packable composites, P60 and
      SureFil, were tested. A dynamic oscillatory test was used to evaluate the storage
      modulus (E'), loss modulus (E''), and loss tangent (tan delta) of the composites
      as a function of frequency (omega) from 0.1 to 20Hz at 23 degrees C. RESULTS: The
      E' and E'' increased with increasing frequency and showed differences in
      magnitude among brands. The complex moduli E* of the composites at omega=2 Hz,
      normalized to that of Z100, were 2.16 (Z250), 4.80 (P60), and 25.21 (SureFil).
      The magnitudes and frequency characteristic of loss tangent differed
      significantly among brands. The relationship among the complex modulus E*, the
      phase angle delta, and the frequency omega was represented by the frequency
      domain phasor form E*(omega)e(idelta)=E*(omega) angledelta. SIGNIFICANCE: The
      viscoelasticities of composites, which influence handling characteristics, are
      significantly different among brands. The VOR is a relatively simple device for
      the dynamic rheological measurement of dental composites. The loci of the
      frequency domain phasor plots in a complex plane are a valuable method of
      representing the viscoelastic properties of composites.

PMID- 16566998
TI  - Multilayered construction of glucose oxidase and silica nanoparticles on Au
      electrodes based on layer-by-layer covalent attachment.
AB  - A feasible approach to construct multilayer films of aminated silica
      nanoparticles/glucose oxidase (ASNPs/GOx) on the Au electrode surface using a
      glutaraldehyde as a covalent attachment cross-linker is described. The covalent
      attachment processes were followed and confirmed by electrochemical impedance
      spectroscopy (EIS), which demonstrated that the ASNPs/GOx multilayer films are
      formed in a progressive and uniform manner. The gold electrodes modified with the
      ASNPs/GOx multilayer films were studied by cyclic voltammetry (CV) and showed
      excellent electro-catalytical response to the oxidation of glucose when
      ferrocenemethanol was used as an artificial redox mediator. From the analysis of
      voltammetric signals, the coverage of active enzyme on the electrode was
      estimated, which showed a linear relationship with the number of ASNPs/GOx
      bilayers. This suggests that the analytical performance such as sensitivity,
      detection limit is tunable by controlling the number of attached bilayers. The
      linear response range of the biosensor constructed with four bilayers of
      ASNPs/GOx to the concentration of glucose can extend at least to 8mM and reached
      95% of the steady-state current in less than 4s with the sensitivity of 5.11
      microA/mM cm(2) and the detection limit of 9 microm. In addition, the sensor
      exhibited good stability and long-term life.

PMID- 16566999
TI  - Differential detergent fractionation for non-electrophoretic bovine peripheral
      blood monocyte proteomics reveals proteins involved in professional antigen
      presentation.
AB  - Professional antigen presenting cells (APC), dendritic cells (DC) and their
      myeloid progenitors, monocytes/macrophages are critical controllers of innate and
      adaptive immunity. Here we show that differential detergent fractionation (DDF)
      analysis of bovine monocytes reveals proteins related to antigen pattern
      recognition, uptake and presentation to immunocompetent lymphocytes. We identify
      53 bovine proteins involved in immune function of professional APC. In
      particular, 13 adhesion molecules, three toll-like receptors (TLR1, 6 and 8),
      three antigen uptake-related proteins (including mannose receptor [MR]
      precursor), and eight actin-like proteins involved in active endocytosis were
      identified. In addition, MHC class I and II-related proteins, cytokines, active
      substances and growth factors have been identified. We conclude that the DDF
      approach can provide interpretable and meaningful functional information
      concerning protein expression profiles associated with monocyte activation,
      transformation into macrophages and/or immature DC, and maturation of monocyte
      derived DC in the presence of multiple bovine pathogens.

PMID- 16567000
TI  - The contributions of Paul Ehrlich to infectious disease.
AB  - Paul Ehrlich (1854-1915) is nowadays considered a pioneer in a number of medical
      fields, and in the course of time his role in the establishment and development
      of disciplines such as histology, immunology, oncology and haematology has been
      acknowledged. Aim of this historical note is to illustrate, in the area of
      chemotherapy, the special importance of this brilliant scientist whose 150th
      anniversary of birth occurred in 2004. Already as a medical student, Ehrlich was
      obsessed by structural organic chemistry and dyes, and, continually studying
      these issues, he elaborated his theory regarding the discovery of a "magic
      bullet", able to specifically destroy tumour cells and micro-organisms. In
      practice he applied methylene blue to the treatment of malaria patients,
      following his intuition that such a dye could destroy parasites. However, his
      culminating achievements in the chemotherapic field, reached even at the expense
      of his health, were the concept of the one-dose treatment of Helicobacter pylori
      infection, and the creation of arsphenamine (compound 606, or Salvarsan), the
      first really effective compound in controlling human syphilis. Within the many
      and various contributions of Ehrlich to the development of experimental and
      clinical medicine, a special mention of his experimental studies and clinical
      applications in the area of chemotherapy is essential, since his achievements in
      this biomedical area remain a paramount legacy in the history of the therapy of
      infections.

PMID- 16567001
TI  - An improved liquid chromatographic method with electrochemical detection for
      direct determination of serotonin in microdialysates from Caudate-putamen and
      pineal gland regions of rat brain.
AB  - A liquid chromatography method coupled with electrochemical detection has been
      developed for the direct measurement 5-hydroxytryptamine (5-HT) and 5
      hydroxyindoleacetic acid (5-HIAA) in brain microdialysates. The separation
      conditions have been optimized to detect only the 5-HT and 5-HIAA in dialysates
      and elute the other monoamines and their metabolites in the void. Linear
      regression analysis of chromatographic peak area as a function of concentration
      in the range 5-1000 pg/mL gave correlation coefficients over 0.995. Sample
      stability and an assay validation for precision and accuracy were also performed.
      The limit of detection (S/N = 3) for 5-HT was 12 femtomol/mL. The method has been
      applied to simultaneously measure extracellular 5-HT and 5-HIAA in brain
      microdialysates from the pineal gland and caudate-putamen of awake and freely
      moving rats under basal conditions.

PMID- 16567002
TI  - Modulation of canine immunosenescence by life-long caloric restriction.
AB  - Caloric restriction (CR) has been shown to retard immunosenescence and to extend
      median and maximum life span in rodent species. Longitudinal effects of CR on the
      canine immune system are presented in this report. A group of 48 Labrador
      Retrievers, divided at weaning into weight- and sex-matched pairs, were
      maintained on a diet restriction protocol from age 8 weeks until death. Each
      restricted dog received 75% of the total food consumed by its control-fed pair
      mate. Immune parameters were monitored from 4 to 13 years. CR retarded age
      related declines in both lymphoproliferative responses and absolute numbers of
      lymphocytes and the T, CD4, and CD8-cell subsets. In females, CR attenuated the
      age-related increase in T-cell percentages and marginally retarded the age
      related increase in memory cell percentages. Age-related changes in B-cell
      percentages and numbers were augmented by CR. No direct effect of CR on
      phagocytic activity of PMN, antibody production or NK cell activity, was
      observed. Lower lymphoproliferative responses, lower numbers of lymphocytes, T,
      CD4 and CD8 cells, lower CD8 percentages and higher B-cell percentages were all
      found to be significantly associated with a decreased likelihood of survival in
      these dogs.

PMID- 16567003
TI  - The sialic acid residue is a crucial component of C. jejuni lipooligosaccharide
      ganglioside mimicry in the induction Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is an autoimmune neuropathy that often follows C.
      jejuni infection. Sialic acid (N-acetylneuraminic acid, NANA) is a common
      constituent of lipooligosaccharide (LOS). The molecular mimicry between C. jejuni
      LOS and human peripheral nerve gangliosides is believed to play an important role
      in the pathogenesis of GBS. The neuB1 encodes NANA synthetase, required for the
      synthesis of NANA of C. jejuni LOS. A neuB1 mutant was constructed from a C.
      jejuni HS:19 wild strain. Mutant LOS could not bind the cholera toxin B subunit,
      failed to induce anti-GM1 antibodies, and did not cause pathological changes in
      the peripheral nerves. These data suggest that the NANA residue in LOS is a
      crucial epitope in realization of ganglioside molecular mimicry.

PMID- 16567004
TI  - Videomanometry reveals clinically relevant parameters of swallowing in children.
AB  - OBJECTIVE: The aim of this pilot study is to demonstrate the technical and
      clinical feasibility of videomanometry to assess swallowing in infants and young
      children presenting with dysphagia. METHODS: We performed videomanometry using a
      combined solid state catheter and a perfused manometric sleeve assembly in eight
      patients (2-28 months) presenting at a tertiary care institution with symptoms of
      dysphagia. Solid state sensors were positioned at the inferior margin of the
      valleculae and the laryngeal entrance and the upper esophageal sphincter sleeve
      assembly was positioned across the upper esophageal sphincter. Manometric and
      radiological data were digitally recorded simultaneously using a manofluoromixer.
      Liquid bolus swallows were recorded in each patient and different geometric
      parameters of deglutition were measured. RESULTS: Placement and fixation of the
      catheter was well tolerated and no adverse effects occurred. The children easily
      swallowed test boluses as selected during clinical examination. Results indicate
      that pharyngeal contractility can be evaluated as well as relaxation of the upper
      esophageal sphincter during swallowing of wet boluses. CONCLUSIONS:
      Videomanometry in young children is feasible with the limited discomfort of the
      placement of the catheter. It is a promising technique that will allow more
      accurate assessment of pediatric oropharyngeal dysphagia.

PMID- 16567005
TI  - Evaluation of a new automated assay for hepatitis B surface antigen (HBsAg)
      detection VIDAS HBsAg Ultra.
AB  - In a multicenter study a new automated screening assay, VIDAS HBsAg Ultra (long
      (L) and short (S) incubation protocol (Biomerieux, Marcy l'Etoile, France), was
      compared to a well established test (AxSYM HBsAg v2, Abbott Diagnostics,
      Wiesbaden, Germany) for the detection of hepatitis B virus (HBV) surface antigen
      (HBsAg). A total of 32 seroconversion panels, sera from the chronic phase of
      infection, dilution series of the WHO standard, S gene mutants (recombinant
      mutants and diluted and undiluted sera harbouring mutants with single or multiple
      amino acid (aa) substitutions, n = 40) and isolated anti-HBc positive samples
      were tested for the evaluation of sensitivity. Sera from HBsAg negative blood
      donors, pregnant women, hospitalized patients and potentially cross-reactive
      samples were investigated to determine the specificity of the new assay. The
      VIDAS HBsAg Ultra (L+S) had a higher sensitivity than the alternative assay for
      the detection of acute hepatitis B in seroconversion panels. The mean time of the
      diagnostic window was shortened with the VIDAS HBsAg Ultra (L) and (S) in
      comparison with the AxSYM HBsAg v2 by 1.06 and 0.66 days, respectively. The VIDAS
      HBsAg Ultra (L) did not detect one diluted sample out of six bearing the single
      aa G145R substitution, and two out of 12 diluted samples harbouring multiple aa
      substitutions. The analytical sensitivity of the assays varied from one surface
      mutant to another. While no false positive results were obtained with the VIDAS
      HBsAg Ultra (L+S) among potentially interfering samples, four false positives
      were detected with the AxSYM HBsAg v2. The respective values for sensitivity for
      the VIDAS HBsAg Ultra (L), (S) and the AxSYM HBsAg v2 were 99.07%, 97.87% and
      94.14%. The specificities were 100% (VIDAS HBsAg Ultra L and S) and 99.6% (AxSYM
      HBsAg v2). In conclusion, the VIDAS HBsAg Ultra is highly sensitive and specific
      and represents an improvement for the detection of HBsAg in routine diagnostic
      laboratories.

PMID- 16567006
TI  - Brief early handling increases morphine dependence in adult rats.
AB  - Short early manipulations of rodent postnatal environment may trigger long-term
      effects on neurobiological and behavioural phenotypes in adulthood. However,
      little is known about such effects of handling on the vulnerability to develop
      drug dependence. The present study aimed to analyze the long-term effects of a
      brief handling (1 min) on morphine and ethanol dependence and on the
      preproenkephalin (PPE) mRNA and mu opioid receptor levels. Handled rats showed a
      significant increase in morphine (25mg/l) but not ethanol (10%) consumption and
      preference after 7 weeks and no difference in morphine (2 and 5mg/kg) conditioned
      place preference. No difference of preproenkephalin mRNA and mu opioid receptor
      levels was detected in the mesolimbic system between both groups. These data
      emphasize that human brief handling, which can lead to morphine dependence
      development, constitutes in itself an experimental treatment and not a control
      condition.

PMID- 16567007
TI  - Glycobiological study of adult Opisthorchis viverrini: characterization of N
      linked oligosaccharides.

PMID- 16567008
TI  - Risk factors and characteristics of falls during inpatient rehabilitation of
      elderly patients.
AB  - The present study investigated the incidence, characteristics, and risk factors
      predictive of falls in different patient populations hospitalized in a geriatric
      rehabilitation hospital. Overall 84 fallers and 84 control patients were enrolled
      in this study. The patients were analyzed into three subgroups: patients
      hospitalized for stroke rehabilitation, hip surgery rehabilitation, and other
      rehabilitation patients. All patients were evaluated for their predisposing and
      situational risk factors for the fall. Each group of fallers was analyzed in
      relation to the control group. Every group was also analyzed in relation to the
      other groups. Risk-taking activity and using wheelchairs were common risk factor
      among patients hospitalized for stroke rehabilitation or hip surgery
      rehabilitation. Vertigo and anti-hypertensive drugs intake were significant
      predictors of falling among all fallers in the hospital. Among Stroke patients'
      vertigo was a significant predictor of falling. Anti-depressant drug intake was
      the only weakly significant predictor of falling among deconditioned patients.
      Patient's falls in a geriatric rehabilitation setting tend to demonstrate
      patterns that may be used to focus prevention strategies. We found that risk
      factors for falls differ between different groups of rehabilitation patients, and
      that the selection of type of patients may affect which combination of risk
      factors is identified.

PMID- 16567009
TI  - Bacteriophages and biotechnology: vaccines, gene therapy and antibacterials.
AB  - In recent years it has been recognized that bacteriophages have several potential
      applications in the modern biotechnology industry: they have been proposed as
      delivery vehicles for protein and DNA vaccines; as gene therapy delivery
      vehicles; as alternatives to antibiotics; for the detection of pathogenic
      bacteria; and as tools for screening libraries of proteins, peptides or
      antibodies. This diversity, and the ease of their manipulation and production,
      means that they have potential uses in research, therapeutics and manufacturing
      in both the biotechnology and medical fields. It is hoped that the wide range of
      scientists, clinicians and biotechnologists currently researching or putting
      phages to practical use are able to pool their knowledge and expertise and
      thereby accelerate progress towards further development in this exciting field of
      biotechnology.

PMID- 16567010
TI  - Effects of the gravitational vertical on the visual perception of reversible
      figures.
AB  - We examined the effects of the gravitational vertical on the perception of
      reversible figures. Each reversible figure had two interpretations depending on
      whether it was viewed vertically in one orientation or upside down. When it was
      presented horizontally, the two interpretations alternated. Subjects were
      required to indicate which interpretation was perceived after briefly viewing the
      horizontal presentation on a head-mounted display. When the subject was upright,
      each interpretation occurred by chance. When the subject was lying on one side,
      the horizontal figure was generally perceived as if it was presented vertically
      with the side down. The results suggest that the perception of reversible figures
      is influenced by the gravitational vertical, which might be reconstructed by
      multimodal integration of vestibular, proprioceptive, and tactile inputs.

PMID- 16567011
TI  - Effect of the dissolved oxygen on the bioproduction of glycerol and ethanol by
      Hansenula anomala growing under salt stress conditions.
AB  - The effect of the dissolved oxygen on glycerol and ethanol productions by an
      osmotolerant yeast Hansenula anomala was examined during growth in media at low
      water activity resulting from the addition of 2M NaCl in the culture medium. High
      stirring rate, high culture medium aeration, as well as high mass transfer
      surface inhibited both glycerol and ethanol biosynthesis. In absence of oxygen,
      yeast used acetaldehyde as a hydrogen acceptor, leading to the stimulation of
      ethanol biosynthesis and accounting for the low biomass and glycerol production;
      the experimental ratio ethanol on glycerol produced was 5.1 when the available
      oxygen was lowered (low stirring rate, 500rpm) and increased to 10.2 in absence
      of aeration. Extracellular glycerol production was therefore optimal for a
      moderate stirring (1000rpm) and aeration (1.4vvm) rates. These optimal conditions
      resulted in an experimental ratio ethanol on glycerol produced of 4.1, namely
      close to the theoretical value of 4, illustrating the osmodependent channelling
      of carbon towards polyols production.

PMID- 16567012
TI  - Effects of cyanide and dissolved oxygen concentration on biological Au recovery.
AB  - The number of discarded electric devices containing traces of Au is currently
      increasing. It is desirable to recover this Au because of its valuable
      physicochemical properties. Au is usually dissolved with relatively high
      concentrations of cyanide, which is associated with environmental risk.
      Chromobacterium violaceum is able to produce and detoxify small amounts of
      cyanide, and may thus be able to recover Au from discarded electric devices. This
      study investigated the effects of cyanide and dissolved oxygen concentration on
      biological Au recovery. Cyanide production by C. violaceum was sufficient to
      dissolve Au, while maintaining a high cyanide concentration did not enhance Au
      dissolution. Increased oxygen concentration enhanced Au dissolution from 0.04 to
      0.16 mmol/l within the test period of 70 h. Electrochemical measurement clarified
      this phenomenon; the rest potential of Au in the cyanide solution produced by C.
      violaceum increased from -400 to -200 mV, while in the sterile cyanide solution,
      it was constant in cyanide concentrations ranging from 0 to 1.5 mmol/l and
      increased in dissolved oxygen concentrations ranging from 0 to 0.25 mmol/l.
      Therefore, it was clarified that dissolved oxygen concentration is the main
      factor affecting the efficiency of cyanide leaching of gold by using bacteria.

PMID- 16567013
TI  - Substrate and inhibitor specificity of class 1 and class 2 histone deacetylases.
AB  - Histone deacetylases (HDACs) are key enzymes in the transcriptional regulation of
      gene expression in eukaryotic cells. In recent years HDACs have attracted
      considerable attention as promising new targets in anticancer therapy. Currently,
      different histone deacetylase subtypes are divided into four groups denoted as
      classes 1-4. Here, we compare in more detail representatives of class 1 HDACs and
      FB188 HDAH as a close bacterial homologue of class 2 HDAC6, in regard of
      substrate and inhibitor specificity. Structure comparison is used to identify
      candidate regions responsible for observed specificity differences. Knowledge of
      these structural elements expedite studies on the biochemical role of different
      HDAC subtypes as well as the development of highly selective HDAC inhibitors as
      antitumor agents.

PMID- 16567014
TI  - Markedly improving Novozym 435-mediated regioselective acylation of 1-beta-D
      arabinofuranosylcytosine by using co-solvent mixtures as the reaction media.
AB  - A comparative study was made of Novozym 435-catalyzed regioselective acylation of
      1-beta-D-arabinofuranosylcytosine with vinyl propionate for the preparation of
      the 5'-O-monoester in eleven co-solvent mixtures and three pure polar solvents.
      Novozym 435 displayed low or no acylation activity toward 1-beta-D
      arabinofuranosylcytosine in pure polar solvents, although those solvents can
      dissolve the nucleosides well. When a hexane-pyridine co-solvent system was
      adopted, both the initial rate and the substrate conversion were enhanced
      markedly. The polarity of co-solvent mixtures had significant effect on the
      reaction. Among the solvent mixtures investigated, the higher the polarity of the
      solvent mixture, the lower the initial reaction rate and the substrate
      conversion. It was also found that the acylation was dependent on the hydrophobic
      solvent content, the water activity and the reaction temperature. The most
      suitable co-solvent, initial water activity, and reaction temperature were hexane
      pyridine (28:72, v/v), 0.07, and 50 degrees C, respectively. Under these
      conditions, the initial rate, the substrate conversion and the regioselectivity
      were as high as 91.1 mM h(-1), >97% and >98%, respectively, after a reaction time
      of 6 h. Among the reaction mediums examined, the lowest apparent activation
      energy was achieved with hexane-pyridine (28:72, v/v), in which Novozym 435 also
      exhibited good thermal stability.

PMID- 16567015
TI  - A protein database constructed from low-coverage genomic sequence of Bacillus
      megaterium and its use for accelerated proteomic analysis.
AB  - Peptide mass fingerprint (PMF) matching is a high-throughput method used for
      protein spot identification in connection with two-dimensional gel
      electrophoresis (2DE). However, the success of PMF matching largely depends on
      whether the proteins to be identified exist in the database searched.
      Consequently, it is often necessary to apply other more sophisticated but also
      time-consuming technologies to generate sequence-tags for definitive protein
      identification. On the other hand, modern sequencing technologies are generating
      a large quantity of DNA sequences, first in unfinished form or with low genome
      coverage due to the time-consuming and thus limiting steps of finishing and
      annotation. We recently started to sequence the genome of Bacillus megaterium DSM
      319, a bacterium of industrial interest. In this study, we demonstrate that a
      protein database generated from merely three-fold coverage, unfinished genomic
      sequences of this bacterium allows a fast and reliable protein spot
      identification solely based on PMF from high-throughput MALDI-TOF MS analysis. We
      further show that the strain-specific protein database from low coverage genomic
      sequence greatly outperforms the commonly used cross-species databases
      constructed from 13 completely sequenced Bacillus strains for protein spot
      identification via PMF.

PMID- 16567016
TI  - The diversity of RNA silencing pathways in plants.
AB  - RNA silencing was discovered in plants as a mechanism whereby invading nucleic
      acids, such as transgenes and viruses, are silenced through the action of small
      (20-26 nt) homologous RNA molecules. Our understanding of small RNA biology has
      significantly improved in recent years, and it is now clear that there are
      several cellular silencing pathways in addition to those involved in defense.
      Endogenous silencing pathways have important roles in gene regulation at the
      transcriptional, RNA stability and translational levels. They share a common core
      of small RNA generator and effector proteins with multiple paralogs in plant
      genomes, some of which have acquired highly specialized functions. Here, we
      review recent developments in the plant RNA silencing field that have identified
      components of specific silencing pathways and have shed light on the mechanisms
      and biological roles of RNA silencing in plants.

PMID- 16567017
TI  - A decade of modeling Alzheimer's disease in transgenic mice.
AB  - It has been over a decade since the first Alzheimer's disease (AD) transgenic
      mouse models were reported. These models have enabled dramatic advances in our
      understanding of the pathogenic mechanism in AD and of potential therapeutic
      approaches to tackling the inexorable clinical progression of the disease. In
      this article, we discuss the current status of AD mouse models and focus on
      recent work that has examined the development of the neuropathological lesions
      observed in AD (plaques and tangles). The relationship between these lesions,
      neurodegeneration and development of the clinical syndrome will be explored.

PMID- 16567018
TI  - Simple sequence repeats as advantageous mutators in evolution.
AB  - Simple sequence repeats (SSRs) often serve to modify genes with which they are
      associated. The influence of SSRs on gene regulation, transcription and protein
      function typically depends on the number of repeats, while mutations that add or
      subtract repeat units are both frequent and reversible. SSRs thus provide a
      prolific source of quantitative and qualitative variation. Over the past decade,
      researchers have found that this spontaneous variation has been tapped by natural
      and artificial selection to adjust almost every aspect of gene function. These
      studies support the hypothesis that SSRs, by virtue of their special mutational
      and functional qualities, have a major role in generating the genetic variation
      underlying adaptive evolution.

PMID- 16567019
TI  - Biologics in development for rheumatoid arthritis: relevance to osteoarthritis.
AB  - The osteoarthritis disease process affects not only the cartilage but also the
      entire joint structure, including the synovium, bone and periarticular muscles.
      Characteristically, abnormal biomechanical forces result in an imbalance between
      chondrocyte anabolic and catabolic pathways, which ultimately leads to
      progressive joint destruction. Within cartilage and synovium, pro-inflammatory
      cytokines, particularly IL-1b and TNF-a, auto-catalytically stimulate their own
      production and induce chondrocytes to produce additional catabolic mediators,
      including proteases, chemokines, nitric oxide, and prostaglandins. The success of
      targeted biological therapy in rheumatoid arthritis has taught that the blockade
      of a single dominant cytokine can lead to remarkable clinical benefit, even in
      complex disease. The effectiveness of biologicals in inflammatory arthritides as
      disease modifying agents has increased the likelihood that similar strategies can
      be developed to target specific molecular mechanisms in osteoarthritis (OA).
      However, since the clinical development program for disease-modifying OA drugs
      (DMOADs) is complicated by the slow progression of disease in many patients, the
      introduction of DMOADs will be greatly enhanced by advances in imaging and
      biomarkers that serve as validated surrogate endpoints for meaningful clinical
      outcomes.

PMID- 16567020
TI  - Secondary cancers after a lung carcinoid primary: a population-based analysis.
AB  - Carcinoid tumors of the lung were first described in 1937, yet little is known
      about their etiology. The aim of the present investigation was to determine if
      there was excess risk of secondary cancers in a population-based sample after a
      lung carcinoid tumor diagnosis which may provide insight to the etiology.
      Subjects were 1882 cases diagnosed with carcinoid tumors of the lung between 1988
      and 2000 whose information was obtained from the Surveillance, Epidemiology and
      End Results (SEER) Program database. Standardized incidence ratios were
      calculated by dividing the observed number of second primary cancers by the
      expected number of cancers. Excess risk of breast cancer was seen following
      diagnosis of a carcinoid tumor (SIR=1.80 95% CI 1.22-2.55). When stratified by
      time after diagnosis, excess risk of breast cancers in women was seen in the
      first 5 years after carcinoid diagnosis (SIR=1.68 95% CI 1.08-2.50) but fewer
      than expected breast cancers were diagnosed greater than 5 years after carcinoid
      diagnosis (SIR=0.29 95% CI 0.09-0.68). Prostate cancers also occurred 2.8 times
      more often than expected (95% CI 1.66-4.43), with risk being elevated only in the
      first 5 years post-carcinoid diagnosis. Development of lung carcinoids may be the
      result of genetic predisposition or environmental exposures, particularly those
      that are hormonally related. The role of genetics and sex hormones in lung
      carcinoid development, as well as the identification of other risk factors,
      should be explored.

PMID- 16567022
TI  - Results of surgery in small cell carcinoma of the lung.
AB  - OBJECTIVE: The experiences published by various groups have re-opened the debate
      on the role of surgery in the management of patients with small cell lung cancer,
      especially in those with early stage disease (T1-T2 N0). Our study reports the
      survival rate of 47 patients with small cell lung cancer treated surgically.
      PATIENTS AND METHODS: Ours is a prospective study that selected patients with
      lung cancer recommended for surgery (n=2994) between 1993 and 1997 based on
      operability criteria accepted by the Bronchogenic Carcinoma Cooperative Group of
      the Spanish Society of Pneumology and Thoracic Surgery. We report the clinical as
      well as pathological stages of the patients with small cell lung cancer (n=47),
      later analysing the 5-year survival rate after surgery using the Kaplan-Meier
      method. RESULTS: In 31 patients (66%), resection was complete; 3 patients (6%)
      received induction treatment and 30 (64%) adjuvant treatment. Five years later,
      26% (95% CI 12-40%) of the patients that received surgical treatment were still
      alive. When we analysed the patients that underwent complete resection, 31% (95%
      CI 13-49%) survived 5 years or more. In patients at stage Ip (n=15), 36% (95% CI
      11-61%) were still living after 5 years. CONCLUSION: Until future studies compare
      surgery plus chemotherapy versus chemotherapy and radiotherapy, it seems
      reasonable to offer surgical treatment to those patients with early stage small
      cell lung cancer (T1-T2-N0).

PMID- 16567021
TI  - Mutations of the epidermal growth factor receptor tyrosine kinase domain and
      associations with clinicopathological features in non-small cell lung cancer
      patients.
AB  - Somatic tyrosine kinase (TK) domain mutations of the epidermal growth factor
      receptor (EGFR) gene are associated with sensitivity of non-small cell lung
      cancer (NSCLC) to tyrosine kinase inhibitors (TKI's), however their incidence in
      distinct populations is not clarified. We sequenced exons 18-21 of the EGFR TK
      domain from 60 Greek and Czech patients, enrolled in an adjuvant chemotherapy
      trial following total resection for stages I-IIIa disease. Somatic mutations were
      found in 9/60 patients (15.0%), several being novel. EGFR mutations were more
      common in Stage I tumors (p = 0.023), they were also more common in women and
      never smokers; however, no other significant association of clinicopathological
      features with mutations was found. Median TTP and OS of patients with and without
      mutations were 13.2 and 40 months compared to 22.9 and 43.2 months, respectively.
      These differences were not statistically significant. K-ras (5/60, 8%) and EGFR
      mutations were found to be mutually exclusive. We identified a wide spectrum of
      somatic EGFR TK mutations reporting a relatively high incidence (15%) in NSCLC
      patients of Greek and Czech origin. As ethnicity seems to be a factor for the
      origin of these mutations, further studies in distinct populations are warranted.

PMID- 16567023
TI  - Clozapine but not haloperidol suppresses the changes in the levels of
      neuropeptides in MK-801-treated rat brain regions.
AB  - Noncompetitive NMDA receptor antagonist (+)MK-801 is known to induce
      neurotoxicity and schizophrenia-like symptomatology where atypical neuroleptic
      clozapine is effective in contrast to typical neuroleptic, haloperidol. Although
      neuropeptides are implicated in memory and cognition, their roles in
      schizophrenia are not well understood. In the present study, we therefore
      examined the possible roles of neuropeptides, cholecystokinin (CCK) and
      somatostatin (SS) in the posterior cingulate/retrosplenial cortices (PC/RSC),
      frontal cortex, and hippocampus of a MK-801-induced schizophrenia-like model rat
      brain. This study further investigated the pretreated effect of atypical versus
      typical neuroleptics on the peptidergic system. SS mRNA and peptide levels
      significantly decreased in the PC/RSC and hippocampus but not in the frontal
      cortex 3 days after 0.5 mg/kg MK-801 treatment whereas CCK mRNA and peptide
      levels significantly decreased in all of the brain regions examined. Pretreatment
      with clozapine but not haloperidol completely recovered the changes in both mRNA
      and peptide levels of SS and CCK in those brain regions. These data suggest that
      peptidergic system in the brain presumably plays an important role in the control
      of negative schizophrenia.

PMID- 16567024
TI  - Nurse teachers' knowledge in curriculum planning and implementation.
AB  - BACKGROUND: Nurses are required to base care on research evidence but research
      findings on nursing practice often suggest that the linkage is poor and
      ritualistic routines often prevail. AIMS: The study explored the origin and
      nature of knowledge utilised by nurse teachers when developing and implementing a
      curriculum. METHODS: In a single, ethnographic case study data were collected
      from two curriculum development and two curriculum implementation groups, using
      interviews, participant observation and documents. The study drew directly on
      Bernstein's theory of the pedagogic device and cultural reproduction. RESULTS:
      Findings suggested that even though nurse education appears to be dominated by
      policies and guidelines produced by state agencies, it was teachers operating at
      institutional and classroom levels who determined what was delivered to student
      nurses as they relied upon their experience of teaching and clinical practice to
      plan and implement curriculum. Notwithstanding both national and local
      aspirations to the contrary, teaching and assessment practices were mostly
      teacher- rather than student-centred, with heavy reliance on propositional
      knowledge. CONCLUSION: The practices identified within this study may induce
      approaches to learning that may be antithetical to delivering research based care
      within a prevailing climate that advocates evidence-based practice, clinical
      effectiveness and governance.

PMID- 16567025
TI  - Biomechanical performance of the new BeadEx implant in the treatment of
      osteoporotic vertebral body compression fractures: restoration and maintenance of
      height and stability.
AB  - BACKGROUND: Vertebral compression fractures are counted among the most common
      complications of osteoporosis. For treatment, a new, alternative implant has been
      developed (BeadEx, Expandis, Hof HaCarmel, Israel). The aim of the present in
      vitro study was to evaluate whether this implant is able to restore the initial
      height and three-dimensional stability after fracture and whether it is able to
      maintain this height and stability during complex cyclic loading. METHODS: The
      BeadEx implant consists of small titanium rolls, which are pressed into the
      vertebral body through specially designed, hollow pedicle screws. The height and
      the three-dimensional flexibility of 18 bisegmental spine specimens (nine T12-L2,
      nine L3-L5) was measured, first, before and after creating a wedge compression
      fracture at the middle vertebral body (L1 resp. L4), second, after treatment of
      the fracture, and, third, during and after complex cyclic loading. The fractures
      were treated either with BeadEx plus internal fixator, BeadEx plus bone cement or
      vertebroplasty for comparison. FINDINGS: The height before fracture could almost
      be restored by BeadEx plus bone cement but not by BeadEx plus fixator and
      vertebroplasty. The total height loss after cyclic loading was smallest with
      BeadEx plus bone cement (in median -4.7mm with respect to the intact specimens)
      but -6.2mm with BeadEx plus fixator and -7.8mm with vertebroplasty. The three
      dimensional stability of the specimens was clearly higher if treated with BeadEx
      plus fixator than with BeadEx plus bone cement or vertebroplasty. INTERPRETATION:
      From a biomechanical point of view, BeadEx plus bone cement can be recommended as
      an alternative to vertebroplasty in the treatment of osteoporotic vertebral body
      fractures. BeadEx plus fixator can be recommended if additional stability is
      needed.

PMID- 16567026
TI  - The influence of sole wedges on frontal plane knee kinetics, in isolation and in
      combination with representative rigid and semi-rigid ankle-foot-orthoses.
AB  - BACKGROUND: In earlier stages of knee osteoarthritis orthotic treatments with
      knee orthoses or modified footwear are often considered. Although the load
      reducing effects of knee orthoses have been well established, wearing modified
      footwear would be more comfortable for the patient and less encumbering. The
      effect of modified footwear on the frontal load of the knee is controversial.
      This article describes the effect of medial or lateral shoe wedges alone or
      together with two different types of ankle-stabilizing orthoses. METHODS: The
      effect on frontal knee loading was measured during standing and walking with
      medially and laterally placed wedges under the sole of the shoe. The wedges were
      also combined with two types of orthotic devices - an Ankle-Foot-Orthosis that
      was rigid in the frontal plane but allowed unrestricted sagittal plane motion and
      an ankle support that was semi-rigid in the frontal plane. Joint loading of 10
      healthy persons (mean (standard deviation): age 34 (9) years, height 178 (4)cm,
      mass 73 (9)kg) was investigated by means of a special measuring device that
      accurately determines static loads (Lasar Posture) and with instrumented gait
      analysis (Vicon/Kistler). FINDINGS: Using a lateral wedge under the sole of the
      shoe (without orthotic support) showed no significant reduction in the mean
      maximal knee moment in the frontal plane. Adding an Ankle-Foot-Orthosis that is
      rigid in the frontal plane resulted in significant reduction in the maximal
      frontal moment from 0.54 Nm/kg to 0.38Nm/kg (p0.01). Using a medial wedge,
      without and with Ankle-Foot-Orthosis, produced a significant increase in the
      maximal frontal moment to 0.59 Nm/kg (p0.05) or 0.67 Nm/kg (p0.01), respectively.
      INTERPRETATION: These results suggest that the application of a sole wedge
      significantly influences frontal knee loading when used in combination with an
      Ankle-Foot-Orthosis that is rigid in the frontal plane.

PMID- 16567027
TI  - Assessment of intermittent trace element pollution by moss bags.
AB  - Moss bags of the aquatic bryophyte Rhynchostegium riparioides (Hedw.) C. Jens.
      were transplanted into an irrigation ditch in the Province of Vicenza (NE Italy),
      affected by intermittent trace element contamination due to galvanics. The study
      aimed at: (a) testing the ability of mosses to detect different patterns of
      pollution, (b) providing information about intensity and temporal extension of
      pollution events, and (c) localising the main sources. Moss bags were collected
      after 20, 34, 48 and 62 days of exposure. The concentrations of As, Cd, Cr, Cu,
      Hg, Mn, Ni, Pb and Zn in the desiccated apical shoots of mosses were determined
      by atomic absorption spectrophotometry. The mean concentrations measured in non
      contaminated stations of a previous work were adopted as background values, to
      calculate the contamination factor (CF). Transplants were able to: (a) detect
      spatial patterns of bioaccumulation, (b) reveal chronic contamination by Pb and
      Cu, intermittent contamination by Cr, Zn, and Ni, and a release of Cd by moss
      bags, and (c) localise the main emission sources.

PMID- 16567028
TI  - Case reports and literature review: the association between reactivation of human
      herpes virus-6 and peripheral white blood cell count in patients with
      carbamazepine-induced hypersensitivity syndrome.
AB  - Eruptions induced by anticonvulsants can often be experienced clinically, and the
      clinical diagnosis of "drug induced hypersensitivity syndrome (HS)" was proposed
      to characterize these drug eruptions. Reactivation of human herpes virus-6 seems
      to be an integral component of HS. Previously, we experienced two cases of
      carbamazepine (an anticonvulsant) induced HS and both cases did not show a
      reactivation of human herpes virus-6 infection (no elevation of anti-human herpes
      virus-6 IgG titres). The features of these two cases were compared with other
      reported cases that presented HS with the reactivation of human herpes virus-6.
      In the early phase of HS, a change in peripheral white blood cell count seems to
      be important and could be used as an indicator to predict whether late phase HS
      with reactivation of human herpes virus-6 will occur, since the increase in white
      blood cell count is seen before the increase in anti-human herpes virus-6 titres.
      Reactivation of human herpes virus-6 may cause severe clinical symptoms such as
      encephalitis. When an increase in white blood cells are observed in HS cases at
      onset, immediate discontinuation of cause drug and intensive care are necessary
      to avoid the more severe symptoms of HS.

PMID- 16567029
TI  - Contamination of mercury in tongkat Ali hitam herbal preparations.
AB  - The DCA (Drug Control Authority), Malaysia has implemented the phase three
      registration of traditional medicines on 1 January 1992. As such, a total of 100
      products in various pharmaceutical dosage forms of a herbal preparation found in
      Malaysia, containing tongkat Ali hitam, either single or combined preparations,
      were analyzed for the presence of a heavy toxic metal, mercury, using atomic
      absorption spectrophotometer, after performing a simple random sampling to enable
      each sample an equal chance of being selected in an unbiased manner. Results
      showed that 26% of these products possessed 0.53-2.35 ppm of mercury, and
      therefore, do not comply with the quality requirement for traditional medicines
      in Malaysia. The quality requirement for traditional medicines in Malaysia is not
      exceeding 0.5 ppm for mercury. Out of these 26 products, four products have
      already registered with the DCA, Malaysia whilst the rest, however, have not
      registered with the DCA, Malaysia.

PMID- 16567030
TI  - Enhancement by dexamethasone of the therapeutic benefits of cisplatin via
      regulation of tumor angiogenesis and cell cycle kinetics in a murine tumor
      paradigm.
AB  - We have investigated in the current study, the possible modulatory effects of
      dexamethasone on cisplatin cytotoxicity in Ehrlich ascites carcinoma (EAC)
      bearing female Swiss albino mice. Cisplatin (3.5mg/kg) was injected IP for 3
      consecutive days in mice previously inoculated SC with EAC cells in the right
      flank. Dexamethasone (2.5mg/kg) was administered SC alone or 24h ahead of
      cisplatin challenge, and these regimens were given for 3 consecutive days.
      Dexamethasone enhanced the anti-tumor effects of cisplatin, clearly demonstrated
      by the increased mean tumor growth time (TGT) and tumor growth delay time (TGDT)
      values compared to cisplatin alone. The effects of dexamethasone on tumor
      angiogenesis and cell cycle distribution of EAC cells have been addressed as
      possible mechanisms, whereby the glucocorticoid could probably augment cisplatin
      cell-kill. Indeed, dexamethasone enhanced the angiostatic activity of cisplatin
      by 52.5%. The glucocorticoid also synchronized the EAC cells in the G2/M phase,
      secondary to its regulatory role on the transcriptional and translational
      activity in these cells, thus, exposing them to the dramatic cytotoxic potential
      of cisplatin. One could conclude that dexamethasone enhanced the anti-tumor
      effects of cisplatin via augmenting its angiostatic activity and modulating cell
      cycle kinetics. Also, dexamethasone did not alter cisplatin-induced
      nephrotoxicity, thus demonstrating an improved therapeutic potential.

PMID- 16567031
TI  - The influence of capsule geometry and cement formulation on the apparent
      viscosity of dental cements.
AB  - OBJECTIVES: This work examines the influence of specific aspects of capsule
      design and cement formulation on the handling properties of the extruded glass
      polyalkenoate cement (GPC) pastes. METHODS: A commercial metal reinforced GPC,
      HiDense, and experimental GPCs were extruded using a tensometer at loads and
      rates maintained within end-user limits and the apparent viscosity of the cement
      paste was determined by applying Poiseuille's law. The influence of the extrusion
      procedure (mixing time and ram speed), capillary geometry (length and diameter)
      and cement composition (powder: liquid (P:L) ratio, tartaric acid content and
      poly(acrylic acid) molar mass) on the apparent viscosity of the cement paste was
      evaluated. RESULTS: The examined GPCs behaved as non-Newtonian, pseudoplastic
      materials and exhibited a yield stress. Variation of the geometry of the capsule
      capillary resulted in the apparent viscosity of HiDense increasing by 7% as the
      length increased from 5 to 15mm whilst halving the capillary diameter from 2 to
      1mm resulted in a 63% decrease in the apparent viscosity and a 600% increase in
      the extrusion load. The apparent viscosity of the experimental GPCs was increased
      by an increase in the P:L ratio and, in general, by the PAA molar mass, whilst
      the concentration-dependent effect of (+)-tartaric acid (TAA) indicates a working
      time dependence on TAA content. CONCLUSIONS: Using this approach optimisation of
      the rheological properties can be achieved by manipulation of the capsule design
      and cement formulation due to the dependency of the apparent viscosity on the
      capillary diameter, TAA content, P:L ratio and poly(acrylic acid) molar mass.

PMID- 16567032
TI  - Clinical performance of posterior metal-free polymer crowns with and without
      fiber reinforcement: one-year results of a randomised clinical trial.
AB  - OBJECTIVES: The aim of this study was to evaluate the clinical performance of
      posterior, metal-free polymer crowns with and without a glass-fiber framework, in
      comparison to metal-ceramic crowns. METHODS: After randomisation, 80 single
      crowns, manufactured from a newly designed polymer composite, were set in
      posterior teeth. Half of these received a glass-fiber framework, while half were
      prepared without any framework stabilisation. All polymer crowns were adhesively
      luted with resin cement. As the control group, 40 conventional metal-ceramic
      crowns were inserted with hybrid cement. Documentation included failures and
      other complications, as well as gingival/plaque status and aesthetic performance.
      RESULTS: During the 12-month observation period, eight polymer crowns and three
      metal-ceramic crowns showed clinically relevant complications. The most frequent
      complications were root canal treatments (n=4) and decementation (n=4) of the
      crowns. A total of two crowns (one polymer crown with fiber network and one crown
      of the control group) had to be replaced. After 12 months, polymer crowns with
      glass-fiber framework exhibited significantly higher plaque accumulation
      (p=0.005) and gingival index (p=0.04) than metal-ceramic crowns, while no
      significant differences could be demonstrated for polymer crowns without fiber
      reinforcement. Postoperative sensibility and aesthetic performance did not differ
      significantly between the groups. CONCLUSIONS: Within a 12-month observation
      period, posterior polymer crowns with and without glass-fiber framework
      demonstrated acceptable stability and aesthetic performance. Polymer crowns with
      fiber framework showed significant higher plaque accumulation and gingival index
      than metal-ceramic crowns.

PMID- 16567033
TI  - Calcium channel blockers for tocolysis: a review of their role and safety
      following reports of serious adverse events.
AB  - The use of nifedipine and other calcium channel blockers has become commonplace
      in the management of preterm labour. Several relatively small randomised trials
      have compared calcium channel blockers with beta-agonists and the meta-analyses
      of these studies have demonstrated superior or comparable efficacy and a superior
      adverse events profile. The safety of calcium channel blockers in pregnancy has
      not been rigorously evaluated and they remain unlicensed for use as tocolytics.
      Indeed, there is concern following a number of recent case studies that have
      reported serious adverse events after the administration of a calcium channel
      blocker as a tocolytic. In this article all these recently reported cases are
      critically reviewed and the pros and cons of tocolytic treatment options are
      discussed. Based on the findings of this review the following recommendations can
      be made with regard to tocolysis with calcium channel blockers: firstly, calcium
      channel blockers should not be combined with intravenous beta-agonists; secondly,
      intravenous nicardipine or high oral doses of nifedipine should not be used in
      cases where the mother is cardiovascular compromised or in cases of multiple
      gestation; finally, blood pressure should be monitored and cardiotocography
      recorded during the administration of immediate release tablets and patients
      should be advised to avoid chewing them. To truly establish the safety of
      tocolytics, all serious adverse effects of tocolytics should be reported to a
      central point and be critically reviewed.

PMID- 16567034
TI  - Continued reduction in the incidence of birth trauma and birth asphyxia related
      to instrumental deliveries after the study period: was this the Hawthorne effect?
AB  - BACKGROUND: The incidence of birth trauma and birth asphyxia related to
      instrumental deliveries in our obstetric unit was high (2.8%) in 1998-1999. A
      study was performed in 2000 to identify the risk factors. Unexpectedly, the
      incidence (0.6%) was reduced significantly during the study period. We attributed
      this phenomenon to the famous Hawthorne effect (tendency to improve performance
      because of awareness of being studied). OBJECTIVES: The objectives were to study
      whether there is a continued reduction in the incidence of birth trauma and birth
      asphyxia related to instrumental deliveries in the post-study period (2001-2003)
      and to investigate the presence of underlying confounding factors apart from the
      Hawthorne effect. METHOD: To compare the hospital obstetric statistics among the
      pre-study period (1998-1999), the study period (2000) and the post-study period
      (2001-2003), in particular the incidence of birth trauma and birth asphyxia
      related to instrumental deliveries, the instrumental delivery rate, the overall
      Caesarean section rate, the Caesarean section rate for no progress of labour, the
      incidence of failed instrumental delivery, the incidence of attempted
      instrumental delivery in the operating theatre, and incidence of direct second
      stage Caesarean sections. RESULTS: The incidence of birth trauma and birth
      asphyxia related to instrumental deliveries (0.6%) during the study period (2000)
      was significantly lower than that (2.8%) during the pre-study period (1998-1999;
      RR 0.27, 95% CI 0.11-0.70). This phenomenon continued into the post-study period
      (2001-2003) when the incidence of 1.0% was similarly lower than that in the pre
      study period (RR 0.35, 95% CI 0.20-0.64). The instrumental delivery rate
      decreased further in the post-study period (13.5%) compared with those in the
      study (16.6%) and pre-study (19.5%) periods (RR 0.81, 95% CI 0.75-0.89 and RR
      0.69, 95% CI 0.65-0.74, respectively). There was a marked increase in the direct
      second-stage Caesarean section rate in the post-study period (7.1%) compared to
      those in the study (0.4%) and pre-study (0.7%) periods (RR 15.9, 95% CI 5.05
      49.73 and RR 9.77, 95% CI 5.28-18.08, respectively). CONCLUSION: A change in
      obstetric practice was identified that may explain the continued reduction in the
      incidence of birth trauma and birth asphyxia related to instrumental deliveries
      in the post-study period.

PMID- 16567035
TI  - Comment to "Peripartum hysterectomy in a teaching hospital in the eastern region
      of Turkey".

PMID- 16567036
TI  - Salvage techniques for phosphodiesterase 5 inhibitor therapy: purposeful but how
      much?

PMID- 16567037
TI  - Apathy in patients with mild cognitive impairment and the risk of developing
      dementia of Alzheimer's disease: a one-year follow-up study.
AB  - OBJECTIVE: To evaluate the relation between apathy and development of dementia in
      patients with amnestic mild cognitive impairment (MCI). METHODS: Two hundred and
      fifty-one French-speaking outpatients fulfilling the criteria of amnestic MCI
      were enrolled. Apathy was assessed with the Apathy Inventory (IA).
      Neuropsychiatric evaluation also included the Goldberg anxiety scale and the
      Montgomery and Asberg Depressive Rating Scale (MADRS). The main end point
      considered after a 1-year follow-up was the development of dementia of Alzheimer
      type (DAT). RESULTS: At baseline there were 86 (39.8%) subjects presenting at
      least one symptom of apathy among the 216 included in analysis. After a 1-year
      follow-up, 22 patients developed DAT. Of the patients with apathy at baseline 13
      (15.1%) developed DAT in comparison with 9 (6.9%) of the non-apathetic patients.
      At the 1-year follow-up, patients developing DAT had a significantly higher
      frequency of apathetic symptoms (91.7%) than patients without DAT (26.9%).
      CONCLUSION: Taking into account that apathy is one of the most frequently
      observed neuropsychiatric symptoms in MCI and in DAT the present study suggests
      that patients with MCI and apathy should be more closely observed.

PMID- 16567038
TI  - Proteomics-based analysis of a pair of glioma cell lines with different tumor
      forming characteristics.
AB  - Glioma is the most common malignant disease in the brain, and recurrence is the
      main cause of death from this disease. Tumor recurrence involves multiple steps,
      and requires the accumulation of the altered expression of many different
      proteins. Identification of the recurrence associated protein profile in glioma
      cell lines will be helpful in clarifying the molecular mechanisms underlying
      glioma recurrence. In this report, two glioma cell lines with distinct tumor
      forming ability in vitro and in vivo were chosen and the different protein
      expression patterns were analyzed by proteomics method. To confirm the utility of
      this method, we validated the differential expression of one protein, cathepsin
      D, by immunohistochemistry analysis. Forty-six proteins appeared differently
      between two cell lines and 18 of them were identified. These 18 are involved in
      cell proliferation, DNA replication, protein synthesis, invasion, angiogenesis
      and neurotrophic factor. All of these molecules are important in tumor growth,
      and a subset of them may be related to glioma recurrence. These findings may
      contribute to the discovery of new diagnostic markers and therapeutic targets of
      glioma.

PMID- 16567039
TI  - Protein tyrosine nitration is associated with cold- and drug-resistant
      microtubules in neuronal-like PC12 cells.
AB  - Among the myriad of cellular functions played by nitric oxide in the brain, there
      is increasing evidence that nitric oxide might be a primary player in the program
      of neurogenesis and neuronal differentiation. We have recently reported that
      tyrosine nitration of proteins is implicated in the signaling pathway triggered
      by nitric oxide during NGF-induced neuronal differentiation in PC12 cells. The
      cytoskeleton becomes the main cellular fraction containing nitrotyrosinated
      proteins, and the cytoskeletal proteins alpha-tubulin and tau are two of the
      targets. Here, we have studied the association of nitrated proteins with the
      cytoskeletal fraction in differentiating PC12 cells following exposure to
      microtubule depolymerising treatments and found that nitration of the
      cytoskeleton correlates with the increased microtubule stability underlying the
      progression of neuronal differentiation. These results suggest a novel functional
      role for nitrated cytoskeletal proteins in the stabilisation of neurites
      occurring in differentiated neuronal cells.

PMID- 16567040
TI  - Antioxidant Cu/Zn SOD: expression in postnatal brain progenitor cells.
AB  - Precursor cells have been shown to be affected by oxidative stress, in vivo and
      vitro, but little is known about the expression of antioxidant mechanisms in
      neuronal/glial differentiation. We have characterized the expression of Cu/Zn
      superoxide dismutase (Cu/Zn SOD), one of the main antioxidant proteins involved
      in the breakdown of superoxide, in the immature rat dorsolateral subventricular
      zone (SVZ), rostral migratory stream (RMS) and hippocampal subgranular zone
      (SGZ). Progenitor cells were identified immunohistochemically on cryostat
      sections by 5'Bromodeoxyuridine (BrdU) incorporation and expressing cells were
      further characterized using double labeling for progenitor markers. In the SVZ,
      only a subpopulation of BrdU+ cells, mostly found in the medial SVZ, expressed
      Cu/Zn SOD. These cells were mostly nestin+ and some were also vimentin+. In
      contrast, in the lateral SVZ few Cu/Zn SOD+/BrdU+ cells were found. These were
      primarily nestin+, vimentin-, showed some PSA-NCAM expression, but only a few
      were NG2+. In the RMS and SGZ virtually all BrdU+ progenitors were Cu/Zn SOD+ and
      expressed nestin and vimentin. Some RMS cells were also PSA-NCAM+. These findings
      show a heterogeneous expression of Cu/Zn SOD in restricted cell types in the
      germinative zones and suggest a role for antioxidant Cu/Zn SOD in progenitor
      cells of the immature rat brain.

PMID- 16567041
TI  - Hippocampus proper distinguishes between identified and unidentified real-life
      visual objects: an intracranial ERP study.
AB  - Converging evidence indicates that the medial temporal lobe participates not only
      in memory but also in visual object processing. We investigated hippocampal
      contributions to visual object identification by recording event-related
      potentials directly from within the hippocampus during a visual object
      identification task with spatially filtered pictures of real objects presented at
      different levels of filtering. Hippocampal responses differentiated between
      identified and unidentified visual objects within a time window of 200-900 ms
      after stimulus presentation: identified objects elicited a small negative
      component peaking around 300 ms (hippocampal-N300) and a large positive
      component, around 650 ms (hippocampal-P600), while the N300 was increased and the
      P600 was reduced in amplitude in response to unidentified objects. These findings
      demonstrate that the hippocampus proper contributes to the identification of
      visual objects discriminating from the very early between identified and
      unidentified meaningful visual objects.

PMID- 16567042
TI  - Biologic and genetic characteristics of Toxoplasma gondii isolates in free-range
      chickens from Costa Rica, Central America.
AB  - The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator
      of the prevalence of T. gondii oocysts in the soil because chickens feed from the
      ground. The prevalence of T. gondii in 144 free-range chickens (Gallus
      domesticus) from Costa Rica was determined. Antibodies to T. gondii were assayed
      by the modified agglutination test (MAT), and found in 60 (40.1%) of 144 chickens
      with titers of 1:5 in 16, 1:10 in 5, 1:20 in 2, 1:40 in 3, 1:80 in 5, and 1:160
      or higher in 29. Tissues of all chickens were bioassayed for T. gondii in mice or
      cats. Hearts and brains of 52 chickens with titers of 1:5 or higher and 16
      chickens with doubtful titers were pooled and bioassayed in mice. Tissues from 76
      chickens with MAT titers of 1:10 or less were pooled and fed to three T. gondii
      free cats. Fecal floats of cats were bioassayed orally in mice but were negative
      for T. gondii oocysts. T. gondii was isolated by bioassay in mice from 32
      chickens with MAT titers of 1:10 or higher. All infected mice from 4 of the 32
      isolates died of toxoplasmosis. Genotyping of these 32 isolates using
      polymorphisms at the loci SAG1, SAG2, SAG3, BTUB and GRA6 revealed five
      genotypes. Five isolates had type I alleles and one isolate had type III alleles
      at all loci. The rest 26 isolates contained the combination of type I and II or I
      and III alleles and were divided into three genotypes. None was found to have
      genotype II alleles at all five loci. This is the first report of genetic
      characterization of T. gondii isolates from Costa Rica, Central America.

PMID- 16567044
TI  - Molecular evidence for the infection of zoo chimpanzees by pig Ascaris.
AB  - We here describe the transmission of the pig roundworm, Ascaris suum to
      chimpanzees maintained in the Copenhagen Zoo, Denmark. Using a technique for
      whole genome fingerprinting, amplified fragment length polymorphism (AFLP) and
      the technique PCR restricted fragment length polymorphism (PCR-RFLP) of the
      internal transcribed spacer region (ITS) of the nuclear ribosomal DNA, the worms
      from the chimpanzees were compared with Ascaris spp obtained from humans and pigs
      in order to identify the source of the infection. By the use of different
      distance and clustering based methods on the AFLP data set the worms from the
      chimpanzees were assigned to the same cluster as that of the worms from pigs. The
      PCR-RFLP analysis supported the AFLP results. Therefore, the zoo chimpanzees have
      required Ascaris infections by cross-infection from pigs. Pigs as a potential
      source of Ascaris infections for both captive and wild chimpanzees and other
      animals, therefore needs to be considered and appropriate steps taken to prevent
      such infection.

PMID- 16567043
TI  - Detection of benzimidazole resistance in Haemonchus contortus using RFLP-PCR
      technique.
AB  - Benzimidazole (BZ) resistance in Haemonchus contortus is linked primarily with
      the mutation in the beta-tubulin isotype 1 gene that substitute phenylalanine
      (Phe) to tyrosine (Tyr) at 200 codon of the gene. In the present study, a new
      restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR)
      technique has been developed for detection of BZ resistance in the beta-tubulin
      isotype 1 gene of H. contortus. The technique utilizes two primers viz. AvikaF
      and AvikaR to amplify the region containing mutation in the beta-tubulin gene
      followed by restriction digestion. After digestion, the 'rr' individuals
      (homozygous resistant) revealed 257 and 48 bp bands, the 'rS' individuals
      (heterozygous) showed 305, 257 and 48 bp bands, while 'SS' individuals
      (homozygous susceptible) revealed uncut 305 bp band. A total of 162 adult male H.
      contortus collected from Avikanagar, Jaipur and Bikaner regions (54 from each
      region) were genotyped for analyzing BZ resistance in the beta-tubulin gene. Out
      of which, 130 adults were 'rr' types, 20 'rS' types and 12 'SS' types. The
      results showed that genotypic frequencies of different genotypes (rr, rS and SS)
      were highly significant difference among the three regions (P<0.001). The 'rr'
      individuals were higher (98%) in Jaipur followed by Avikanagar (93%) and Bikaner
      (50%) regions. Overall, the prevalence of BZ resistant allele (r) was higher
      (86%) as compared to BZ susceptible allele (S) (14%). The technique was also
      found suitable for genotyping of larvae of H. contortus and yielded reproducible
      results. The study indicated that RFLP-PCR is an easy, reproducible and less
      expensive than allele specific PCR. This technique will be helpful in
      establishing the prevalence rate of BZ resistance in H. contortus and can also be
      utilized for existing worm control programme.

PMID- 16567045
TI  - Hematological and biochemical changes in water buffalo calves (Bubalus bubalis)
      infected with Trypanosoma evansi.
AB  - Four water buffalo calves (Bubalus bubalis) were each inoculated intravenously
      with 10(6)T. evansi (camel isolate) and the fifth calf kept as non-infected
      control. The blood and sera of all calves were examined every 4 days during the
      first month post-inoculation (pi) and then once weekly until the end of the
      experiment (88 days pi). They were examined for hematological and biochemical
      changes, liver and kidney function tests. Hemoglobin concentration (Hb%), packed
      cell volume (PCV) and red blood cell count were significantly decreased. Total
      leucocytic count, lymphocytes and monocytes showed significant increase. Liver
      function tests revealed significant elevation in the activity of lactate
      dehydrogenase enzyme (LDH), globulin, total biliruben and indirect biliruben
      while alkaline phosphatase enzyme showed significant decrease. Kidney function
      tests revealed significant decrease of both creatinine and urea.

PMID- 16567046
TI  - Montenegro's skin reactions and antibodies against different Leishmania species
      in dogs from a visceral leishmaniosis endemic area.
AB  - In this study, humoral (circulating anti-Leishmania antibodies) and cellular
      (Montenegro's skin test) immune responses of dogs from an endemic area of
      visceral leishmaniosis were tested using Leishmania chagasi, Leishmania
      amazonensis and Leishmania braziliensis antigens. The antibody response was
      tested in three animal groups, selected according to their anti-L. chagasi
      antibody activity, as measured by ELISA in the serum: 19 negative (O.D. below
      0.30), seven with undefined (O.D. between 0.40 and 0.70) and 12 positive (O.D.
      above 1.0) ELISA result. In the group of animals with positive ELISA, the
      antibody activity against L. chagasi antigens (mean O.D.=1.31) was significantly
      higher (ANOVA, P<0.01) than against L. amazonensis (mean O.D.=0.88) or L.
      braziliensis (mean O.D.=0.87) antigens. The Montenegro's skin test results
      obtained with L. chagasi and L. braziliensis antigens showed a fair agreement
      (kappa=0.309). The same was observed when antigens from L. braziliensis and L.
      amazonensis were compared (kappa=0.374), whereas a moderate agreement between the
      results from tests performed with L. chagasi and L. amazonensis antigens was
      observed (kappa=0.530). The induration areas obtained with L. braziliensis
      antigen were smaller than those obtained with the other antigens. The data
      presented herein indicate that the use of antigens from different Leishmania
      species may interfere with the results of the immunological tests performed in
      dogs in an endemic area of visceral leishmaniosis.

PMID- 16567047
TI  - Two serine proteases from Anopheles dirus haemocytes exhibit changes in
      transcript abundance after infection of an incompatible rodent malaria parasite,
      Plasmodium yoelii.
AB  - Serine proteases are involved in regulation of innate immune responses, such as
      haemolymph coagulation, melanization reaction and antimicrobial peptide
      synthesis. Although several serine proteases have been characterized in Anopheles
      gambiae (A. gambiae), few were cloned from other malaria vectors. In this study,
      we identified three cDNA fragments of serine proteases (AdSp1, AdSp2 and AdSp3)
      from haemocytes of an oriental malaria vector, Anopheles dirus (A. dirus), by
      cloning of fragments amplified with degenerate primers into the T-vector. RT-PCR
      analysis demonstrated that both AdSp1 and AdSp3 genes were also expressed in
      salivary gland. Basic local alignment search tool (BLAST) search found that both
      AdSp1 and AdSp3 were highly similar in sequence to A. gambiae Sp14A and Sp14D2,
      insects prophenoloxidase activating enzyme (PPAE) and Drosophila protease easter.
      Semi-quantitative RT-PCR indicated the transcription level of both AdSp1 and
      AdSp3 in haemocytes of A. dirus infected with Plasmodium yoelii (P. yoelii) was
      significant higher than that fed on 5% glucose or normal mouse blood at 7 days
      after the infectious meal (p<0.05), when P. yoelii oocysts began to be melanized
      by A. dirus. Our results indicated that both AdSp1 and AdSp3 might play an
      important role during melanotic encapsulation of P. yoelii by A. dirus.

PMID- 16567048
TI  - Comparison of infection rates of Oestrus ovis between sheep and goats kept in
      mixed flocks.
AB  - Oestrosis is a nasal myiasis of sheep and goats caused by larvae of the fly
      Oestrus ovis and can lead to severe clinical signs, which together with the
      disturbance caused by the adult fly may result into serious economic losses.
      Infection rates and larval burdens are always higher in sheep than in goats after
      either natural or artificial infestation. The aim of this study was to compare
      the host preference of the adult fly O. ovis between sheep and goats in mixed
      flocks, where they are kept together under the same husbandry conditions and
      hence, are very similarly exposed to the fly preference. Blood sera samples were
      collected from a total of 397 sheep and 335 goats, from 43 mixed flocks located
      at different regions of Greece. Antibodies specific to O. ovis IgG were measured
      by ELISA. A flock was considered positive when at least one individual was
      positive, i.e. showed a seropositivity of >or=20% in relation to positive control
      sera. A total of 193 (48.6%) sheep and 58 (17.9%) goats were found to be
      seropositive against O. ovis. Thirty-eight (88.4%) out of 43 flocks had at least
      one seropositive animal. The mean seroconversion against O. ovis in animals from
      the different flocks was 38.6% and 13.6% for sheep and goats, respectively,
      whereas the variance of infection within each flock was 0-100%. The mean
      seropositivity between sheep that were found to be positive or negative was 60.6%
      and 5.4%, respectively, whereas the corresponding values between goats were 35.2%
      and 5.2%, respectively. No significant difference in the seroconversion values
      was noted between flocks from the different areas (P=0.817), whereas a very
      significant difference was observed between animal species (P=0.001). However,
      there was no significant difference when seroconversion comparisons were made
      within samples of the same animals species, sheep or goats from different flocks
      of all the regions included in the study (P=0.695). The results of this study
      clearly demonstrate that O. ovis has a widespread distribution in Greece, and the
      seroprevalence is significantly higher in sheep than goats (P=0.001).

PMID- 16567049
TI  - High prevalence of Trypanosoma brucei gambiense group 1 in pigs from the Fontem
      sleeping sickness focus in Cameroon.
AB  - To understand the importance of domestic pigs in the epidemiology of human
      trypanosomiasis, PCR was used to identify trypanosome populations in 133 pigs
      from the Fontem sleeping sickness focus of Cameroon. The results from this study
      show that 73.7% (98/133) of pigs from the Fontem area carry at least one
      trypanosome species. Trypanosoma vivax, T. brucei s.l. and T. congolense forest
      were found in 34.6% (46/133), 40.0% (53/133) and 46.0% (61/133) of the pigs
      respectively. T. simiae and T. congolense savannah were not identified in these
      animals. The use of repeated DNA sequences detected T. b. gambiense group 1 in
      14.8% (15/101) of the pigs. Such pigs can be possible reservoir hosts for T. b.
      gambiense group 1 and contribute to the maintenance of the disease in the area.
      Mixed infections were revealed in 35.3% (47/133) of the pigs. Furthermore, we
      observed that under natural conditions, 52.4% (11/21) of the pigs from the Fontem
      focus carry mixed infections with T. b. gambiense group 1. No significant
      difference was observed between the percentage of T. b. gambiense group 1 single
      and mixed infections, and between the prevalence of this trypanosome in pigs from
      villages with and without sleeping sickness patients.

PMID- 16567050
TI  - Evaluation of buparvaquone (BUTA-Kel KELA, Belgium) as a treatment of East Coast
      fever in cattle, in the peri-urban of Dar Es Salaam city, Tanzania.
AB  - Evaluation trials of the efficacy of buparvaquone (BUTA-kel KELA Laboratoria,
      N.V. Belgium), as a treatment of field cases of Theileria parva infection (East
      Coast fever - ECF) were carried out on 63 cattle in the peri-urban of Dar Es
      Salaam city, Tanzania, during the period November 2004 to August 2005. Thirty-two
      cattle (56%) received single-dose treatment (2.5 mg buparvaquone per kg body
      weight), while two and three-dose treatment with interval(s) of 48 h was given to
      33% and 11% of total treated cattle, respectively; 38 cattle (60.3%) were treated
      at an early stage of the disease, while 25 cattle (39.7%) were treated at an
      advanced stage of the disease. The rectal body temperature of 90.5% of
      buparvaquone-treated cattle dropped to normal values (37.5-39.5 degrees C) by day
      7 of treatment, and by day 15 of treatment 96.8% of treated cattle showed normal
      values. Pulmonary signs were observed in 8/68 (11.8%) of total ECF diagnosed
      cattle and were successfully treated, albeit with parvaquone plus frusemide
      (Fruvexon); were not included in final evaluation of the efficacy of BUTA-kel.
      The present evaluation trials record a recovery rate of 95.2%. Buparvaquone (BUTA
      kel KELA Laboratoria, N.V. Belgium), therefore, records another efficacious and
      valuable alternative treatment against East Coast fever in Tanzania.

PMID- 16567051
TI  - An expanded adenylate kinase gene family in the protozoan parasite Trypanosoma
      cruzi.
AB  - Adenylate kinases supply energy routes in cellular energetic homeostasis. In this
      work, we identified and characterized the adenylate kinase activity in extracts
      from the flagellated parasite Trypanosoma cruzi, the causative agent of Chagas'
      disease. Adenylate kinase activity was detected in different subcellular
      fractions and the cytosolic isoform was biochemically characterized. Cytosolic
      adenylate kinase specific activity increases continuously during the epimastigote
      growth and is down-regulated when other soluble phosphotransferase, arginine
      kinase, is overexpressed. Six different genes of adenylate kinase isoforms were
      identified and the mRNA expression was confirmed by RT-PCR and Northern Blot.
      Three open reading frames coding for different enzyme isoforms named TzADK1,
      TzADK2 and TzADK5 were cloned and functionally expressed in E. coli. This work
      reports an unusually large number of genes of adenylate kinases and suggests a
      coordinated regulation of phosphotransferase-mediated ATP regenerating pathways
      in the unicellular parasite Trypanosoma cruzi.

PMID- 16567052
TI  - Measurement of protein turnover rates by heavy water labeling of nonessential
      amino acids.
AB  - In vivo measurements of protein synthesis using isotope-labeled amino acids (AAs)
      are hampered by the heterogeneity of AA pools and, for slow turnover proteins,
      the difficulty and expense of long-term labeling. Continuous oral heavy water
      (2H2O) labeling can safely maintain stable body water 2H enrichments for weeks or
      months. 2H is metabolically incorporated into C-H bonds of nonessential AAs
      (NEAAs) and hence into proteins. No posttranslational label exchange occurs, so
      2H incorporation into protein NEAAs, in principle, reports on protein synthesis.
      Here, we show by mass isotopomer distribution analysis (MIDA) of 2H2O-labeled
      rodent tissue proteins that metabolic 2H flux into C-H bonds of Ala, Gly, or Gln
      used for protein synthesis is nearly complete. By 2H2O labeling of rodents,
      turnover of bone and muscle mixed proteins was quantified and stimulation of
      liver collagen synthesis by CCl4 was detected. Kinetics of several human serum
      proteins were also measured, reproducing published t1/2 estimates. Plateau
      enrichments in Ala varied among different proteins. Moderate amounts of protein,
      isolated chromatographically or electrophoretically, sufficed for kinetic
      analyses. In conclusion, 2H2O labeling permits sensitive, quantitative,
      operationally simple measurements of protein turnover in vivo by the rise-to
      plateau approach, especially for proteins with slow constitutive turnover.

PMID- 16567053
TI  - The calcium-sensitive large-conductance potassium channel (BK/MAXI K) is present
      in the inner mitochondrial membrane of rat brain.
AB  - Large-conductance voltage- and calcium-sensitive channels are known to be
      expressed in the plasmalemma of central neurons; however, recent data suggest
      that large-conductance voltage- and calcium-sensitive channels may also be
      present in mitochondrial membranes. To determine the subcellular localization and
      distribution of large-conductance voltage- and calcium-sensitive channels, rat
      brain fractions obtained by Ficoll-sucrose density gradient centrifugation were
      examined by Western blotting, immunocytochemistry and immuno-gold electron
      microscopy. Immunoblotting studies demonstrated the presence of a consistent
      signal for the alpha subunit of the large-conductance voltage- and calcium
      sensitive channel in the mitochondrial fraction. Double-labeling
      immunofluorescence also demonstrated that large-conductance voltage- and calcium
      sensitive channels are present in mitochondria and co-localize with mitochondrial
      specific proteins such as the translocase of the inner membrane 23, adenine
      nucleotide translocator, cytochrome c oxidase or complex IV-subunit 1 and the
      inner mitochondrial membrane protein but do not co-localize with calnexin, an
      endoplasmic reticulum marker. Western blotting of discrete subcellular fractions
      demonstrated that cytochrome c oxidase or complex IV-subunit 1 was only expressed
      in the mitochondrial fraction whereas actin, acetylcholinesterase, cadherins,
      calnexin, 58 kDa Golgi protein, lactate dehydrogenase and microtubule-associated
      protein 1 were not, demonstrating the purity of the mitochondrial fraction.
      Electron microscopic examination of the mitochondrial pellet demonstrated gold
      particle labeling within mitochondria, indicative of the presence of large
      conductance voltage- and calcium-sensitive channels in the inner mitochondrial
      membrane. These studies provide concrete morphological evidence for the existence
      of large-conductance voltage- and calcium-sensitive channels in mitochondria: our
      findings corroborate the recent electrophysiological evidence of mitochondrial
      large-conductance voltage- and calcium-sensitive channels in glioma and cardiac
      cells.

PMID- 16567054
TI  - Cyclooxygenase-2 mediates the development of cortical spreading depression
      induced tolerance to transient focal cerebral ischemia in rats.
AB  - We examined the role of cyclooxygenase-2 in the development of ischemic tolerance
      induced by cortical spreading depression against transient, focal brain ischemia.
      Cortical spreading depression was continuously induced for 2 h with topical KCl
      (13+/-1 depolarizations/2 h) in male Wistar rats. At 1, 2, 3, 4, and 5 days
      following recovery, the middle cerebral artery was transiently occluded for 120
      min. Four days later, the animals were killed and infarct volume was determined.
      Additionally, cyclooxygenase-2 levels in the cerebral cortex and 15 deoxy
      Delta(12, 14) PGJ2 levels in cerebrospinal fluid were determined at these times
      with Western blotting and immunoassay, respectively. Infarct volume was reduced
      compared with non-cortical spreading depression control animals (274.3+/-15.3
      mm3) when cortical spreading depression was performed 3 and 4 days before middle
      cerebral artery occlusion (163.9+/-14.2 mm3, 154.9+/-14.2 mm3) but not at 1, 2
      and 5 days (280.4+/-17.3 mm3, 276.3+/-16.9 mm3 and 268.5+/-17.3 mm3).
      Cyclooxygenase-2 levels increased most dramatically starting at 2 days, peaked at
      3 days, and started to return toward baseline at 4 days after cortical spreading
      depression. 15 Deoxy-Delta(12, 14) PGJ2 levels increased from 134.7+/-83 pg/ml at
      baseline to 718+/-98 pg/ml at 3 days. Administration of N-[2-cyclohexyloxy-4
      nitrophenyl] methanesulphonamide (10 mg/kg, i.v.), a selective cyclooxygenase-2
      inhibitor, at 1 h prior to middle cerebral artery occlusion in cortical spreading
      depression preconditioned animals did not affect infarct volume (162.6+/-62.1
      mm3). However, administration of N-[2-cyclohexyloxy-4-nitrophenyl]
      methanesulphonamide given three times prior to middle cerebral artery occlusion
      prevented the reduced infarct volume induced by cortical spreading depression
      preconditioning (272.9+/-63.2 mm3). Administration of L-nitro-arginine methyl
      ester (4 mg/kg, i.v.) prior to cortical spreading depression blocked increases in
      cyclooxygenase-2 normally seen at 3 and 4 days. We conclude that NO-mediated
      cyclooxygenase-2 upregulation by cortical spreading depression protects the brain
      against ischemic damage.

PMID- 16567055
TI  - The psychometric properties of the Chinese version of the Fagerstrom Test for
      Nicotine Dependence.
AB  - This study examined the psychometric properties of the Chinese version of the
      Fagerstrom Test for Nicotine Dependence (FTND). Criterion validity, factorial
      structure, and construct reliability were conducted using PRELIS 2 and LISREL 8.7
      software. Two hundred and forty-five adult smokers were recruited from April to
      August 2005 in Taiwan. Because some items of the FTND are dichotomous and
      ordinal, biserial and polyserial correlations between the items and saliva
      cotinine levels were utilized. Confirmatory factor analyses (CFA) were performed
      to compare the relative fit of three competing models. Computation of the
      construct reliability was necessitated by a lack of tau-equivalence. The results
      demonstrated that the Chinese version has satisfactory validity and reliability.
      One item, "Smoke more in the morning," had low correlations with saliva cotinine.
      CFA found the items of the Chinese version were best modeled as two correlated
      factors without a cross-loading. These findings differ from the previous research
      testing the English version. Studies addressing the specific features of
      cigarette dependence in different socio-cultural contexts are needed.

PMID- 16567056
TI  - Looking for boomerang effects: a pre-post experimental study of the effects of
      exposure of youth to television advertising for nicotine replacement therapy and
      Zyban.
AB  - In the context of concerns about unintended "boomerang" influences of
      advertising, this study aimed to examine effects of nicotine replacement therapy
      (NRT) and Zyban advertising on youth perceptions of the ease of quitting, health
      risks of smoking and future intentions to smoke. 718 youth aged 14-16years were
      randomly allocated to view four television ads promoting either: NRT; Zyban; non
      pharmaceutical cessation services (telephone Quitline); or non-cessation messages
      on sun protection. Questionnaire measures were administered before and after
      viewing ads. There were no effects of advertising exposure on perceived health
      effects of smoking or intentions to smoke. Compared with the sun protection ads,
      but not the Quitline ads, those exposed to NRT ads reported stronger perceptions
      about the ease of quitting, but non-susceptible non-smokers primarily drove this
      difference. This study suggests that exposure to NRT and Zyban advertising in an
      experimental context does not reliably influence youth smoking-related beliefs,
      especially those vulnerable to becoming regular smokers.

PMID- 16567057
TI  - Smoking for weight control: effect of priming for body image in female restrained
      eaters.
AB  - Women are more likely than men to believe that smoking helps to control their
      weight, and this relationship may be more pronounced in those with eating
      disturbances, such as eating restraint. Restrained eaters have been shown to be
      more susceptible to media portrayals of idealized body image, like those used in
      tobacco advertising. The primary aim of this study was to examine the effect of
      an implicit prime for body image on expectations that smoking can control weight
      in restrained and non-restrained eaters. Participants were 40 females, who smoked
      an average of 7.65 (S.D.=4.38) cigarettes per day. Participants were presented
      with a bogus task of rating slides; either participants viewed 30 slides of
      nature scenes (neutral prime); or viewed 30 slides depicting fashion models (body
      image prime). Participants then completed questionnaires that assessed smoking
      expectancies, smoking history, and eating restraint. As hypothesized, restrained
      eaters who viewed the slides depicting models had greater likelihood ratings that
      smoking helps to control appetite and manage weight, in comparison to restrained
      eaters who viewed the control slides and non-restrained eaters who viewed either
      type of slides. There were no other group differences across the remaining
      smoking expectancy factors. Images similar to those used in tobacco advertising
      targeting women had the ability to elicit stronger beliefs that smoking is
      beneficial for weight control in a group of women who are at heightened risk for
      such beliefs.

PMID- 16567058
TI  - Gender and weight concerns in adolescent smokers.
AB  - The aim of this study was to examine smoking-specific weight concerns in a well
      characterized sample of adolescent daily smokers and the influence of gender,
      age, and body mass index (BMI). Adolescent smokers (n=103) were asked two smoking
      specific weight concern questions: "How much do cigarettes help you control your
      weight?" and "How concerned are you about gaining weight as a result of
      quitting?" A significant positive relationship was found between average daily
      cigarette use and belief in smoking as a means to control weight and a
      significant negative relationship between the years of smoking and belief that
      smoking controls weight. There was no significant relationship between BMI and
      smoking to control weight for females, whereas for males, there was a positive
      relationship, indicating that heavier males were more likely to report smoking to
      control weight. Additionally, females who smoked more cigarettes reported more
      concern about gaining weight upon quitting, a pattern not seen in males. Results
      highlight potentially important gender differences in the relationship between
      weight concerns and smoking and the influence these concerns may have on quitting
      smoking.

PMID- 16567060
TI  - Regulatory challenges for new formulations of controlled substances in today's
      environment.
AB  - The pharmaceutical industry has made substantial innovations in the area of
      targeted drug delivery and optimization of pharmacokinetics for existing drugs to
      try to maximize therapeutic effect while simultaneously minimizing adverse
      consequences of medication abuse. These innovations, however, have not come
      without a price. Designer drugs and high content modified release formulations
      have been exploited both in casual recreational drug abuse as well as, on a much
      larger scale, by the criminal diversion of these products for profit. In this
      paper we will consider the challenges before manufacturers and regulators as they
      approach the problem of abuse potential of these new drug products and some of
      the solutions specifically designed to counteract abuse.

PMID- 16567059
TI  - Antioxidant activity of Maytenus ilicifolia root bark.
AB  - Maytenus ilicifolia is an important plant with potential on cancer treatment and
      has been largely used in Brazil and other countries. We have evaluated the crude
      ethanolic extract of M. ilicifolia as a potential antioxidant source using an
      assay based on the bleaching of the radical monocation 2,2'-azinobis (3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS(*+)) and by HOCl scavenger capacity.
      Trolox and uric acid were used as positive controls. The results indicated M.
      ilicifolia root bark as a great source of antioxidants based on its potential as
      scavenger of radicals.

PMID- 16567061
TI  - Characterization of the human EDF-1 minimal promoter: involvement of NFY and Sp1
      in the regulation of basal transcription.
AB  - Endothelial Differentiation Factor (EDF)-1 is a calmodulin binding protein
      involved in the repression of endothelial cell differentiation, a crucial, late
      step in angiogenesis. Its expression is cell cycle regulated, although its
      transcriptional regulation is yet to be determined. To map the promoter region
      and to understand its regulation, we cloned and fused 2300 bp upstream of EDF-1
      translational start site to a luciferase reporter gene. After transient
      transfection in HeLa cells, this fragment was shown to possess a promoter
      activity. Deletion constructs of the 5' flanking region of EDF-1 lead to the
      identification of the minimal promoter region which was highly homologous to the
      mouse sequence. No TATA box was detected, whereas three consensus sequences--two
      GC boxes and a CAAT box--were identified. EMSA supershift and chromatin
      immunoprecipitation demonstrated that these sequences were binding sites for
      Sp1/Sp3 and NFY, respectively. Deletion of Sp1/Sp3 and NF-Y consensus sequences
      resulted in the total loss of EDF-1 promoter activity. Our studies indicate that
      Sp1 and NFY binding is essential for EDF-1 promoter activity.

PMID- 16567062
TI  - Insight into the complex genetic network of tetraploid Atlantic salmon (Salmo
      salar L.): description of multiple novel Pax-7 splice variants.
AB  - Paired box transcription factor 7 (Pax-7) cDNA was isolated from the skeletal
      muscle and brain of alevin and adult stages of Atlantic salmon, identifying 10
      variants categorised as novel or established insertions (ins) or deletions (del).
      Two putative Pax-7 paralogs were identified (denoted Pax-7alpha and Pax-7beta) on
      the basis of the length and sequences of intron 3 (218 and 248 bp) and versions
      of ins1 and ins2. Pax-7beta contained a threonine variant of ins1
      (GQY[T]GPEYVYCGT), and a shortened variant of ins2 (GEAS). Pattern identification
      revealed the threonine variant of ins1 includes a potential phosphorylation site
      (casein kinase II). Thus, the tetraploid Atlantic salmon genome appears to
      contain at least two putative copies and multiple splice variants of Pax-7. In
      situ hybridisation localised Pax-7 to mononuclear cells in the fast muscle of
      adult Atlantic salmon, while quantitative real-time PCR showed Pax-7alpha to be
      more highly expressed in brain than in skeletal muscle.

PMID- 16567063
TI  - Origin and evolution of the TKDP gene family.
AB  - The placenta is arguably the most diverse mammalian organ, and several gene
      families expressed in trophoblast tissue are evolving unusually rapidly. The
      trophoblast Kunitz domain protein (TKDP) gene family arose relatively recently
      within the Artiodactyla order in the lineage leading to modern day ruminants.
      Each contains a classical Kunitz-type serine peptidase inhibitory domain at the
      carboxyl-terminus and one or more unique N-domains preceded by the signal
      peptide/propeptide (SP/PP) region. We isolated, mapped and fully sequenced the
      ovine (ov) TKDP-1 gene. Making use of available cDNA sequences to other TKDP
      family members and recent information from the bovine genome sequence, we have
      been able to make inferences about the origin and evolution of the entire gene
      family. The crucial event that created the initial TKDP gene was when a short
      exon was inserted into the intron that separated the sequences encoding the SP/PP
      and Kunitz domains of an ancestral Kunitz gene. This short exon was flanked by
      endogenous retroviral repetitive elements that likely promoted subsequent
      duplication events to provide a tripartite N-domain containing three repeats.
      This three-exon structure further duplicated once in its entirety to provide the
      progenitor of the present day ovTKDP-1 gene, which has two N-domains, and most
      probably twice to provide the progenitor of the bovine TKDP-1 gene, which has
      three N-domains. The TKDPs provide an example of a gene family that is evolving
      rapidly by whole gene duplication, intragenic duplication events, and selection
      for amino acid (aa) change.

PMID- 16567064
TI  - PCR detection of virulence factor genes in Escherichia coli isolates from weaned
      piglets with edema disease and/or diarrhea in China.
AB  - Fimbriae, toxins and pathogenicity islands (PAIs) are main virulence factors of
      the pathogenic Escherichia coli strains. To investigate into their prevalence in
      clinical E. coli isolates associated with porcine postweaning diarrhea (PWD)
      and/or pig edema disease (ED), 240 isolates were obtained from diseased piglets
      (140 from PWD, 76 from ED and 24 from ED/PWD) and submitted to PCR detection for
      genes coding for fimbriae, enterotoxins, shiga toxins, intimin and high-molecular
      weight protein 2 (HMWP2). Among the 240 isolates detected, detection rates of the
      genes for F18, F4, intimin, HMWP2, Stx2e, LTa, STa and STb were 26.25%, 3.75%,
      28.33%, 16.67%, 35%, 10.83%, 14.58% and 9.17%, respectively, and 67.92% of the
      isolates could be assigned into 20 different virulence factor patterns. Further
      more, F18ab+ STEC are the prevalent pathogens of ED, and F18+ and/or intimin+
      STEC/ETEC are the dominant pathogens of ED/PWD, while F18ab+, F4+ and/or intimin+
      ETEC and HPI+ and/or LEE+ E. coli are more frequently associated with PWD.

PMID- 16567065
TI  - The significance of under- or overweight during childhood as a risk factor for
      hypertensive diseases in pregnancy.
AB  - Hypertensive diseases in pregnancy are still a major cause of foetal and maternal
      mortality. Known risk factors allow identification of only a small number of
      patients at risk of developing such a complication. However, better knowledge of
      the risk profile would improve an early adequate monitoring of these pregnancies.
      We therefore investigated the correlation between under- or overweight during
      childhood and the development of hypertensive diseases during pregnancy. The
      study was designed as a cross-sectional case control study. A self-administered
      questionnaire was distributed to 2600 women, who had contacted the German pre
      eclampsia self-help group for information on hypertensive diseases in pregnancy
      and 1233 control women recruited in different hospitals. Diagnosis according to
      criteria of the international society for hypertensive diseases in pregnancy was
      based on medical records. 766 women with a hypertensive disease during their
      pregnancy and 951 control women with normal pregnancies were evaluated after
      verifying for exclusion criteria and complete data sets. Student t-test, chi
      square test and multivariate logistic regression models were used for statistical
      analysis. A history of under- (OR 2.1, 95% CI 1.23-3.61) or overweight (OR 1.46,
      95% CI 1.01-2.12) during childhood is associated with an increased risk for
      hypertensive diseases in pregnancy, which is at least partly independent of pre
      pregnancy BMI. In combination with other risk factors, a history of under- or
      overweight during childhood will help to identify patients at risk for
      hypertensive diseases in pregnancy.

PMID- 16567067
TI  - Effects of toluene inhalation exposure on olfactory functioning: behavioral and
      histological assessment.
AB  - Exposure to pollutant or toxic substances is known to induce adverse health
      effects but few studies have been devoted to study the impact on olfactory
      functioning although neuroreceptors in the nasal cavity are directly in contact
      with volatile molecules. Thus, this work was designed to evaluate in mice the
      potential modifications of the olfactory functioning during (1 month) and after
      (1 month) a prolonged toluene exposure at both sensitive/perceptive and cellular
      levels. Mice were exposed to 1000ppm of toluene for 5h/day, 5days/week for 4
      weeks. Firstly, behavioral evaluation (T-maze test) to toluene sensitivity showed
      a constant decrease during all the 4 weeks of exposure (W1-W4) which continued
      during 2 weeks after the exposure (W5, W6). In contrast, during the last 2 weeks
      of the experiment (W7, W8), the sensitivity of mice to toluene went back to
      normal. Secondly, structural modifications, i.e. density of cells and thickness
      of olfactory epithelium were observed soon after the outset of exposure. The
      number of cells did not change at the beginning of exposure (W1, W2), decreased
      markedly later (W3, W4), increased significantly the first week of the recovery
      period (W5) and stayed stable during the following weeks (W6-W8). Concerning the
      thickness of neuroepithelium, the results at W1 showed a decrease followed by an
      increase suggesting an inflammatory process (W2, W3). In contrast, the results of
      W4 revealed an abrupt decrease of the thickness whereas the return to normal
      arose immediately at the outset of recovery period.

PMID- 16567066
TI  - Effects of benzo-a-pyrene on oxytocin-induced Ca2+ oscillations in myometrial
      cells.
AB  - Benzo-a-pyrene (BaP) is a polycyclic aromatic hydrocarbon that exists as a major
      environmental pollutant. The effect of this carcinogen/mutagen upon myometrial
      Ca(2+) signaling in a human myometrial cell line (PHM1) was examined. Exposure of
      cells to BaP did not alter basal Ca(2+) levels or the inositol(1,4,5)
      trisphosphate-releasable Ca(2+) pool. However, BaP significantly decreased the
      initial oxytocin-induced Ca(2+) transient and the frequency of oxytocin-induced
      Ca(2+)oscillations as well as delayed their onset. To determine the specific
      effects of BaP, pharmacologic agents that target intracellular Ca(2+) homeostasis
      mechanisms were used. Genistein (a non-specific tyrosine kinase inhibitor) and
      AG1478 (an epidermal growth factor receptor blocker) markedly reduced the
      oxytocin-induced Ca(2+) oscillations in control, but had no effect in BaP treated
      cells. Addition of epidermal growth factor or serum before or after oxytocin
      restored the Ca(2+) oscillations in BaP treated cells to a level similar to
      control cells, while the K(+) channel blocker tetraethylammonium chloride,
      partially restored the Ca(2+) response. These data suggest that the tyrosine
      kinase pathway, which is part of the G-protein coupled receptor pathway response
      to oxytocin in PHM1 cells, is a target of BaP action and that EGF or serum can
      restore the oxytocin-induced Ca(2+) oscillations.

PMID- 16567068
TI  - Assessment of screening evaluations is not straightforward Comment on:
      "Comparison of screening questionnaires for the diagnosis of hypogonadism" [J.E.
      Morley, H.M. Perry III, R.T. Kevorkian, P. Patrick, Maturitas 53 (2006) 424-429].

PMID- 16567069
TI  - Synthesis and study of controlled release of ibuprofen from the new acrylic type
      polymers.
AB  - New acrylic type polymeric systems having degradable ester bonds linked to
      ibuprofen were synthesized and evaluated as materials for drug delivery.
      Methacryloyloxy(2-hydroxy)propyl-4-isobutyl-alpha-methylphenyl acetate (MOPE), a
      new methacrylic derivative of ibuprofen in which the drug is separated from the
      methacrylic backbone by an oxy(2-hydroxy)propylene spacer arm and hydrolytically
      labile ester bond, was synthesized from reaction of glycidyl methacrylate with
      ibuprofen. The resulting drug containing monomer was copolymerized with
      methacrylamide, 2-hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or n-butyl
      methacrylate by free radical polymerization method in N,N-di-methylformamide
      (DMF) solution, utilizing azobisisobutyronitrile as initiator at the temperature
      range 65-70 degrees C. The obtained polymers were characterized by FT-IR, 1H NMR
      and 13C NMR spectroscopy. Gel permeation chromatography (GPC) was used for
      determination of average molecular weights of drug-polymer conjugates and showed
      that the polydispersity indices of the polymers are in the range of 1.9-2.3. Drug
      release studies were performed by hydrolysis in buffered solutions (pH 1 and 8)
      at 37 degrees C. Detection of hydrolysis by UV spectroscopy at selected interval
      showed that the drug can be released by selective hydrolysis of the ester bond at
      the side of drug moiety. The release profiles indicated that the hydrolytic
      behavior of polymeric prodrugs is strongly based on the hydrophilicity of polymer
      and the pH of the hydrolysis solution. The hydrophilic polymers containing
      ibuprofen were hydrolyzed in buffer solutions rather than the hydrophobic
      polymers.

PMID- 16567071
TI  - Influence of rheological behaviour of particulate/polymer dispersions on liquid
      filling characteristics for hard gelatin capsules.
AB  - Lactose/poloxamer dispersions were prepared by mixing under vacuum to achieve a
      de-aerated mix with good capsule filling properties and disperse phase uniformity
      at 70 degrees C. Satisfactory capsule filling of molten dispersions was achieved
      up to a limiting concentration of disperse phase, dependent on particle size
      distribution and continuous phase viscosity. Lactose/poloxamer dispersions
      exhibited thixotropic shear thinning behaviour with an abrupt increase in
      apparent viscosity above a limiting concentration of disperse phase. There was a
      good correlation between satisfactory filling of molten dispersions into capsules
      and apparent viscosity of the formulation, whereas, the pronounced increase in
      apparent viscosity resulted in unsatisfactory filling above a critical
      concentration of disperse phase. The rheological data was analysed in detail
      using empirical models and also used to identify capsule filling problems at
      extrudate shear rates for flow from hopper to pump (12 s(-1)) and from nozzle to
      capsule (340 s(-1)).

PMID- 16567070
TI  - Preparation and characterization of mucoadhesive polymer-coated nanoparticles.
AB  - The transmucosal routes such as pulmonary, nasal and oral routes are most
      important and common routes for drug delivering to the body. However, peptide and
      protein drugs are degraded before they reach the blood stream and cannot cross
      the mucosal barriers. The mucoadhesive polymer-coated nanoparticles colloidal
      carriers can solve these problems. In the present investigation, mucoadhesive
      polymer-coated nanoparticles were prepared by emulsion polymerization process. A
      detailed preparation procedure of the mucoadhesive polymer-coated nanoparticles
      was provided. The parameters such as portion of the mucoadhesive polymers and
      concentration of the radical initiator were investigated. The resulting chitosan
      coated nanoparticles colloids possessed positive surface charge, while
      poly(acrylic acid)-coated nanoparticles colloids and carbopol-coated
      nanoparticles colloids had negative surface charge. These nanoparticles were
      suitable for carrying hydrophilic protein or peptide drugs. Chitosan-coated
      nanoparticles were stable when pH value below 11, while poly(acrylic acid)-coated
      nanoparticles and carbopol-coated nanoparticles were stable under physiological
      pH conditions. Therefore, they are promising for transmucosal drug delivery.

PMID- 16567072
TI  - Novel sustained release, swellable and bioadhesive gastroretentive drug delivery
      system for ofloxacin.
AB  - Oral sustained release gastroretentive dosage forms offer many advantages for
      drugs having absorption from upper gastrointestinal tract and improve the
      bioavailability of medications that are characterized by a narrow absorption
      window. A new gastroretentive sustained release delivery system was developed
      with floating, swellable and bioadhesive properties. All these properties were
      optimized and evaluated. Various release retarding polymers like psyllium husk,
      HPMC K100M and a swelling agent, crosspovidone in combinations were tried and
      optimized to get the release profile for 24 h. Formulations were evaluated for in
      vitro drug release profile, swelling characteristics and in vitro bioadhesion
      property. The in vitro drug release followed Higuchi kinetics and the drug
      release mechanism was found to be of anomalous or non-Fickian type. For the
      developed formulation, the value of n was found to be 0.5766 while for the
      marketed formulation the value was 0.5718 indicating the anomalous transport. The
      high water uptake leading to higher swelling of the tablet supported the
      anomalous release mechanism of ofloxacin. The similarity factor f2 was found to
      be 91.12 for the developed formulation indicating the release was similar to that
      of the marketed formulation (Zanocin OD). The swelling properties were increased
      with increasing crosspovidone concentration and contributed significantly in drug
      release from the tablet matrix. The bioadhesive property of the developed
      formulation was found to be significant (P < 0.005) in combination as compared to
      HPMC K100M and psyllium husk alone.

PMID- 16567073
TI  - Cholesterol and triglycerides lowering activities of caraway fruits in normal and
      streptozotocin diabetic rats.
AB  - The purpose of this study was to examine the effect of single and repeated oral
      administration of the aqueous extract of Carum carvi L. fruits at a dose of
      (20mg/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats
      (STZ). After a single oral administration, Carum carvi extract produced a
      significant decrease on triglycerides levels in normal rats (p<0.05). In STZ
      diabetic rats, cholesterol levels were decreased significantly 6h after Carum
      carvi treatment (p<0.05). On the other hand, repeated oral administration of
      Carum carvi extract exhibited a significant hypotriglyceridemic and
      hypocholesterolemic activities in both normal (p<0.01 and <0.001 respectively)
      and STZ diabetic rats (p<0.001) 15 days after Carum carvi treatment. We conclude
      that the aqueous extract of Carum carvi (20mg/kg) exhibits a potent lipid
      lowering activity in both normal and severe hyperglycemic rats after repeated
      oral administration of Carum carvi aqueous extract.

PMID- 16567074
TI  - Intracranial sewing needle in a man with seizure: a case of child abuse?
AB  - Physical abuse in infancy can cause persistent neurological deficits. Although
      intracranial foreign bodies are generally secondary to penetrating trauma or
      surgical procedures, rarely they also occur as a result of child abuse. A 32-year
      old man presented with the complaint of generalized tonic clonic seizures to the
      Neurology Department of Marmara, University Hospital. Computerized tomography
      (CT) scan revealed a sewing needle located within the temporal lobe. The location
      and the position of the needle suggested that it must have been introduced in
      infancy through the lamdoid suture before the closure of it, as an unsuccessful
      deliberate homicide attempt or accidental injury.

PMID- 16567075
TI  - Coronal reformations of the chest on 64-row multi-detector row CT: evaluation of
      image quality in comparison with 16-, 8- and 4-row multi-detector row CT.
AB  - PURPOSE: To evaluate image quality of coronal reformations of chest performed on
      64-row MDCT in comparison with 16-, 8- and 4-row MDCT. MATERIALS AND METHODS:
      Consecutive patients who underwent pulmonary CT angiography using four different
      MDCT scanners were retrospectively studied with IRB approval: (1) n=30, 64-row
      MDCT; (2) n=30, 16-row MDCT; (3) n=30, 8-row MDCT; (4) n=30, 4-row MDCT. Coronal
      reformatted images (2 mm thickness and 2mm intervals for 64-row MDCT; 5 mm
      thickness and 5 mm intervals for 16-, 8- and 4-row MDCT) were evaluated by
      consensus reading of two board-certified radiologists who were blinded to scanner
      type. The image quality of overall chest appearance and individual thoracic
      structures including heart, aorta and pulmonary arteries was graded using five
      point scale. Grades from four different scanners were compared using Kruskal
      Wallis test. A second evaluation was performed in 48 randomly selected patients
      (12 patients for each scanner). Reproducibility was assessed using weighted-kappa
      analysis. RESULT: Significant reproducibility was observed between the first and
      second evaluations in 48 patients both for image quality of overall chest
      (weighted kappa=0.826) and each thoracic structure (mean weighted kappa=0.803;
      range, 0.729-0.858). Image quality of overall chest and individual thoracic
      structures differed significantly among four different MDCT groups, with 64-row
      MDCT having the highest grades, followed by 16-, 8- and 4-row MDCT (mean grades
      for overall chest in each scanner: 3.9, 3.0, 2.4 and 1.9, respectively) (P<0.0001
      for overall chest and each thoracic structure). CONCLUSION: When comparing
      coronal reformations of chest using four different MDCT scanners, the 64-row MDCT
      had the highest image quality for overall chest appearance and individual
      thoracic structures, followed by 16-, 8- and finally 4-row MDCT.

PMID- 16567076
TI  - Noise properties for three weighted Feldkamp algorithms using a 256-detecotor row
      CT-scanner: case study for hepatic volumetric cine imaging.
AB  - In cone-beam geometry, image quality may be degraded or artifacts may occur if
      the cone angle is substantially wide. This is because a cone-beam scan along a
      circular orbit does not collect the complete set of data required to make an
      exact reconstruction of all volumetric data. To increase temporal resolution and
      thus image quality in cone-beam geometry, Silver proposed the new half-scan
      algorithm (NHS-FDK), which extends Parker's weighting function (HS-FDK) by
      utilizing a larger range up to 2pi. Here, we evaluated these algorithms for
      hepatic contrast-enhanced CT in cine scan mode using a 256-detector row CT. The
      full-scan (FS-FDK) images show uniform distribution of the image noise and CT
      number uniformity. Image noise and CT-number uniformity with HS-FDK and NHS-FDK
      images follow the initial projection angle. HS-FDK images therefore have more
      changeable higher intensity (brighter) and a lower intensity (darker) areas than
      respective FS-FDK and NHS-FDK images. We concluded that, considering the trade
      off between image quality and temporal resolution, the NHS-FDK algorithm is
      useful in volumetric cine imaging for the abdomen.

PMID- 16567077
TI  - The role of salvage surgery for recurrence of esophageal squamous cell cancer.
AB  - AIM: A consensus treatment strategy for recurrent esophageal squamous cell cancer
      (ESCC) has not been established. The purpose of the present study was to analyse
      the mode of recurrence, and evaluate the role of surgical salvage treatment in
      recurrence of ESCC. METHODS: Recurrence was detected in 131 of 367 consecutive
      patients with ESCC. We retrospectively analysed the mode of recurrence and
      treatment for recurrence. Recurrence was divided into four types; lymph node,
      hematogeneous, mixed and local. Treatments were classified into four groups;
      chemotherapy alone (C group), radiation therapy +/- chemotherapy (R group),
      surgery +/- other therapy (S group), and no therapy (N group). RESULTS: Of the
      131 recurrences, the number of patients with lymph node, hematogeneous, mixed and
      local recurrence was 43, 44, 40 and 4, respectively. The number of patients in
      the C, R, S, N groups was 35, 35, 24 and 37, respectively. Of the 24 patients who
      received surgical treatment for recurrence, the number of patients with lymph
      node, hematogeneous, mixed and local recurrence was 11, 6, 6 and 1, respectively.
      The number of lesions in hematogeneous recurrence was 2 or less. The survival
      rate from recurrence to death in the C, R, S and N groups was 0, 3.9, 6.7 and 0%,
      respectively. A statistically significant difference was found in these groups (p
      < 0.0001). CONCLUSIONS: Salvage surgery is one of the useful treatment tools for
      resectable metastatic lesions. In such cases, the number of lesions, recurrent
      sites and effectiveness of chemotherapy and/or radiotherapy should be carefully
      evaluated.

PMID- 16567078
TI  - Effect of dietary vegetable and animal proteins on atherothrombosis in mice.
AB  - OBJECTIVE: It is believed that vegetable and fish, but not animal, proteins
      prevent thrombosis. The present study compared the effect of long-term intake of
      purified vegetable and animal proteins (casein, pork, egg white, chicken, white
      and red fish, soybean, and potato) and powders from whole vegetable and animal
      meats (soybean, pork, chicken, and horse mackerel) on thrombotic tendency.
      METHODS: Western-style high-fat diets with various proteins were given to mice
      deficient in apolipoprotein-E and low-density lipoprotein receptor for 8 or 12
      wk. Thrombotic tendency was assessed by a laser-induced thrombosis test, severity
      of atherosclerosis was assessed by morphometric analysis of the aortic lesions,
      and reactivity of platelets was measured by a shear-induced platelet function
      test. RESULTS: There was no difference in thrombotic tendency between the
      vegetable and animal protein diets with the exception of pork protein, which
      showed a prothrombotic effect. The latter was not observed in animals kept on a
      high-protein diet. Thrombotic tendency was not affected by preparation of dietary
      powders from whole pork, chicken, or horse mackerel meats and casein (control),
      all of which contained the same percentages of protein and lipid. In contrast,
      soybean powder showed an antithrombotic effect, which was mainly due to an
      inhibition of atherogenesis rather than to platelet inhibition. CONCLUSION:
      Neither the purified animal nor the vegetable protein diet affected thrombotic
      tendency. Soybean powder inhibited atherothrombosis mainly by inhibiting the
      atherosclerotic process.

PMID- 16567079
TI  - Dental and skeletal changes following surgically assisted rapid maxillary
      expansion.
AB  - The aim of this study was to evaluate skeletal and dental changes after
      surgically assisted rapid maxillary expansion (SARME). Clinical trials were
      carried out that assessed skeletal and dental changes through cephalograms,
      computer tomographs or dental casts. No other simultaneous treatment during the
      active expansion period was accepted. Electronic databases (Pubmed, Medline,
      Medline In-Process & Other Non-Indexed Citations, All Evidence-based Medicine
      Reviews, Embase, Web of Science and Lilacs) were searched. Abstracts which
      appeared to fulfil the selection criteria were selected by consensus. The
      original articles were then retrieved and evaluated with a methodological
      checklist. Their references were hand searched for possible missing articles.
      Only 12 articles fulfilled the selection criteria. All presented methodological
      flaws. An individual methodological analysis of these articles was made.
      Expansion was greater at the molars and diminished progressively to the anterior
      part of the dental arch in all the evaluation periods. Vertical and sagittal
      skeletal changes were nil or not clinically significant. The nasal portion of the
      maxillary complex showed an increase in dimensions thereby improving nasal
      patency. An overall dental relapse of 0.5-1 mm is reported after 1 year of
      orthodontic treatment. The conclusions should be considered with caution because
      only a secondary level of evidence was found.

PMID- 16567080
TI  - Comorbid posttraumatic stress disorder is associated with suicidality in male
      veterans with schizophrenia or schizoaffective disorder.
AB  - The purpose of this study was to determine if patients with schizophrenia or
      schizoaffective disorders and comorbid posttraumatic stress disorder (PTSD) are
      at higher risk for suicidality than patients without comorbid PTSD. Participants
      were 165 male veterans with primary diagnoses of schizophrenia or schizoaffective
      disorder. Those with comorbid PTSD reported higher rates of suicidal ideation and
      suicidal behaviors compared to those without comorbid PTSD. These findings
      suggest that patients with comorbid PTSD are at higher risk for suicidality.
      Enhanced screening and targeted interventions may be warranted to address
      comorbid PTSD and increased suicide risk in this population.

PMID- 16567081
TI  - Meta-analysis of association between ApoE epsilon4 allele and schizophrenia.
AB  - Several case-control studies have reported an association between schizophrenia
      and the epsilon4 allele of Apolipoprotein E gene. The results have been
      equivocal. This meta-analysis has evaluated the collective evidence for an
      association between the epsilon4 allele of Apolipoprotein E gene and
      schizophrenia. We analyzed published data sequentially first considering epsilon4
      allele itself, and then epsilon4 carrier status as risk factors for schizophrenia
      using a sample of 17 population-based case-control studies, of which 6 were from
      Asian and 11 from Caucasian populations. The pooled odds ratios from the
      Caucasian populations showed a modest association with risk of schizophrenia for
      epsilon4 allele and epsilon4 carrier genotype. No other alleles or genotypes were
      significant in either Asian or Caucasian populations when analysed separately or
      combined, although the sample size had over 80% power to detect a significant
      odds ratio of 1.9 in Asian-population studies and 1.6 in Caucasian-population
      studies. After allowing for sensitivity analysis of the studies and assessment of
      publication bias, we conclude that the epsilon4 allele of Apolipoprotein E does
      not play a major role in risk of schizophrenia in Caucasian populations. Since
      significant heterogeneity was present among the 6 Asian populations reported to
      date, further studies using larger sample sizes are required.

PMID- 16567082
TI  - Evidence of semantic disorganisation using semantic priming in individuals with
      high schizotypy.
AB  - Semantic processing deficits are present in schizophrenia and are particularly
      evident on semantic priming tasks. Using high schizotypes (psychosis-prone
      individuals) can overcome some confounds involved in studying actively
      symptomatic schizophrenics. In the current study, 26 high and 32 low scorers on
      the O-LIFE schizotypy scale (from a sample of 251 students) were selected for
      testing. All subjects were administered a lexical-decision semantic priming task
      where half the stimuli had a short 200 ms stimulus onset asynchrony (SOA, length
      of time from onset of prime to onset of target) and half the stimuli had a long
      750 ms SOA. In addition, half the words were of high frequency and half of a low
      frequency. There were no group differences in priming for words of different
      frequencies. Low schizotypes showed greater priming at the 200 ms SOA than at the
      750 ms SOA, whilst individuals with high schizotypy showed the opposite pattern.
      The pattern shown by the low schizotypes replicates earlier work by the authors
      using other normal control samples; establishing that there is greater priming
      under conditions of automatic spreading of activation. Furthermore, the data
      shows there is not an increase in automatic spreading of activation in
      individuals with high schizotypy. There has been controversy in the schizophrenia
      literature over whether there is increased priming under automatic conditions.
      The current study suggests that, when confounds are controlled for, schizophrenia
      like symptoms are not related to an increase in automatic spreading of
      activation.

PMID- 16567083
TI  - Heparin coating durability on artificial heart valves studied by XPS and
      antithrombin binding capacity.
AB  - The durability and functionality of a heparin coating on artificial heart valve
      leaflets were evaluated with X-ray photoelectron spectroscopy (XPS) and by the
      coatings' capacity to bind antithrombin. Current methods for accelerated life
      time testing are based on exposing leaflets to water solutions. In this paper a
      method is explored, in which heart valve leaflets were exposed to a continuous
      high shear rate (4 L/min) of human citrated plasma. It was found that the heparin
      coating was stable and wear resistant enough to still be present after 3 weeks
      and to have about the same antithrombin uptake as coatings not exposed to
      circulating plasma. It was, however, partly destroyed by the test as found using
      XPS. We suggest that heparin chains from the upper layer of heparin have been
      torn off from the carrier chain, in combination with loss of heparin conjugate
      and plasma deposition in patches. This study showed that XPS provides additional
      information to biological measurements such as antithrombin uptake. XPS is
      therefore a valuable technique not only to characterize biomaterials but also to
      evaluate the effect of a performance test.

PMID- 16567084
TI  - Mechanosensitive synoviocytes: a Ca2+ -PKCalpha-MAP kinase pathway contributes to
      stretch-induced hyaluronan synthesis in vitro.
AB  - Hyaluronan (HA) is central to joint function, contributing to synovial fluid
      retention, lubrication, matrix organisation and joint embryogenesis. HA synthesis
      by intimal synoviocytes is stimulated by stretch (SSHA), linking HA production to
      joint usage; but the signal transduction paths are unknown. Low passage rabbit
      synoviocytes (RS), cultured from micro dissected synovial intima, were subjected
      to 10min of 10% static stretch followed by 170-min relaxation, or to sustained
      stretch for 180min in a Flexcell 2000 apparatus. Medium HA content was analysed
      by a HA-binding assay. The roles of protein kinase C (PKC) isoforms,
      extracellular signal-regulated kinases (ERK1/2) and Ca(2+) signalling in SSHA
      were tested using kinase inhibitors, Ca(2+) chelators and Ca(2+) channel
      activators combined with Western blots for activated kinases. Stretch increased
      HA secretion by 57%, independently of stretch duration. PKCalpha translocated
      from cytosol to membrane and triggered the phosphorylation of ERK1/2. The PKC
      inhibitor bisindolylmaleimide (BIM) blocked both SSHA and ERK phosphorylation, as
      did Go 6976, a specific inhibitor of Ca(2+)-dependent PKC. The Ca(2+) channel
      activator Bay K stimulated HA secretion and ERK phosphorylation. Extra- and intra
      cellular Ca(2+) chelation by EGTA and BAPTA-AM (respectively) inhibited SSHA.
      SSHA was also blocked by the partially selective protein kinase A inhibitor, H
      89. Connective tissue growth factor, CTGF, was not involved in SSHA. Thus,
      stimulation of synoviocyte HA secretion by static stretch is due at least in part
      the o activation of a Ca(2+) influx-dependent activation of the PKCalpha-MEK
      ERK1/2 cascade. This is functionally important because it links joint lubrication
      to joint use.

PMID- 16567086
TI  - Dietary gamma-linolenate attenuates tumor growth in a rodent model of prostatic
      adenocarcinoma via suppression of elevated generation of PGE(2) and 5S-HETE.
AB  - Prostate cancer poses considerable threat to the aging male population as it has
      become a leading cause of cancer death to this group. Due to the complexity of
      this age-related disease, the mechanism(s) and factors resulting in prostate
      cancer remain unclear. Reports showing an increase risk in prostatic cancer with
      increasing dietary fat are contrasted by other studies suggesting the beneficial
      effects of certain polyunsaturated fatty acid (PUFA) in the modulation of tumor
      development. The n-6 PUFA, gamma-linolenic acid (GLA), has been shown to suppress
      tumor growth in vitro. Therefore, using the Lobund-Wistar (L-W) rat model of
      prostate cancer, we tested the hypothesis whether dietary supplementation of GLA
      could suppress tumor growth and development in vivo. Prostatic adenocarcinomas
      were induced in two groups of L-W rats, the experimental group (N-nitroso-N
      methylurea, NMU/testosterone propionate, TP) and the GLA group (NMU/TP/GLA fed)
      undergoing similar treatment but fed a purified diet supplemented with GLA. Our
      findings revealed a decrease in prostate growth in the NMU/TP/GLA-fed group as
      determined by weight, tissue size, DNA content and prostate-specific antigen
      (tumor marker of prostate cancer). Comparison between the two groups showed a
      significant increase in 5S-hydroxyeicosatetraenoic acid and prostaglandin E(2) in
      the NMU/TP group. These increases paralleled the increased protein expression and
      activity of cyclooxygenase-2 as well as increased activity of 5-lipoxygenase.
      Taken together, the findings showed that intake of GLA-enriched diet does reduce
      prostatic cancer development in L-W rats and could serve as a non-toxic adjunct
      in management of human prostatic cancer.

PMID- 16567085
TI  - The N-terminal 70-kDa fragment of fibronectin binds to cell surface fibronectin
      assembly sites in the absence of intact fibronectin.
AB  - Binding of the N-terminal 70-kDa (70K) fragment of fibronectin to fibroblasts
      blocks assembly of intact fibronectin and is an accurate indicator of the ability
      of various agents to enhance or inhibit fibronectin assembly. Such binding is
      widely thought to be to already assembled fibronectin. We evaluated this
      hypothesis with fibronectin-null mouse fibroblasts plated on laminin-1 in the
      absence of intact fibronectin. As a proteolytic fragment or recombinant protein,
      70K bound fibronectin-null cells specifically in linear arrays that extended
      outwards from the periphery of spread cells. At early time points, these arrays
      were similar to those formed by intact fibronectin. 70K arrays formed within 5
      min following ligand addition at concentrations as low as 5 nM, indicating rapid
      and high affinity binding. Bound 70K was extractable with Triton X-100 or
      deoxycholate but became insoluble when cross-linked with a membrane-impermeable
      agent into large SDS-stable complexes. Intact fibronectin, in contrast, became
      progressively non-extractable in the absence of cross-linking. The detergent
      resistant arrays of cross-linked 70K localized to tips of cellular extensions and
      partially overlapped with alpha6 and beta1 integrin subunits at the base of the
      extensions. alpha5 did not localize with 70K arrays, but became progressively co
      localized with assemblies of intact fibronectin over time. These results support
      a model in which the 70-kDa region of fibronectin binds to linearly arrayed cell
      surface molecules of adherent cells to initiate assembly, display of the arrays
      is controlled by the integrin that mediates adhesion, and fibronectin-binding
      integrins promote fibronectin-fibronectin interactions during progression of
      assembly.

PMID- 16567087
TI  - Olfactory cell-based biosensor: a first step towards a neurochip of bioelectronic
      nose.
AB  - Human olfactory system can distinguish thousands of odors. In order to realize
      the biomimetic design of electronic nose on the principle of mammalian olfactory
      system, this article reports an olfactory cell-based biosensor as a real bionic
      technique for odorants detection. Effective cultures of olfactory receptor
      neurons and olfactory bulb cells have been achieved on the semiconductor chip.
      Using light-addressable potentiometric sensor (LAPS) as sensing chip to monitor
      extracellular potential of the neurons, the response under stimulations of the
      odorants or neurotransmitters, such as acetic acid and glutamic acid, was tested.
      The results demonstrate that this kind of hybrid system of LAPS and olfactory
      neurons, which is sensitive to odorous changes, has great potential and is
      promising to be used as a novel neurochip of bioelectronic nose for detecting
      odors.

PMID- 16567089
TI  - Karyopherin flexibility in nucleocytoplasmic transport.
AB  - Recent structural work on nuclear transport factors of the importin-beta
      superfamily of karyopherins has shown that these proteins are superhelices of
      HEAT repeats that are able to assume different conformations in different
      functional states. The inherent flexibility of these helicoids facilitates the
      accommodation of different binding partners by an induced-fit type of mechanism.
      Moreover, the energy stored by distorting these molecules may partially balance
      binding energies to enable assembly and disassembly of their complexes with
      relatively small energy changes. Flexibility appears to be an intrinsic feature
      of such superhelices and might be functionally important not only for
      karyopherins and nuclear transport, but also for HEAT repeat proteins from other
      biological systems.

PMID- 16567090
TI  - Structure of the rhodopsin dimer: a working model for G-protein-coupled
      receptors.
AB  - G-protein-coupled receptors (GPCRs) participate in virtually all physiological
      processes. They constitute the largest and most structurally conserved family of
      signaling molecules. Several class C GPCRs have been shown to exist as dimers in
      their active form and growing evidence indicates that many, if not all, class A
      receptors also form dimers and/or higher-order oligomers. High-resolution crystal
      structures are available only for the detergent-solubilized light receptor
      rhodopsin (Rho), the archetypal class A GPCR. In addition, Rho is the only GPCR
      for which the presumed higher-order oligomeric state has been demonstrated, by
      imaging native disk membranes using atomic force microscopy (AFM). Based on these
      data and the X-ray structure, an atomic model of Rho dimers has been proposed, a
      model that is currently scrutinized in various ways. AFM has also been used to
      measure the forces required to unfold single Rho molecules, thereby revealing
      which residues are responsible for Rho's stability. Recent functional analyses of
      fractions from solubilized disk membranes revealed that higher-order Rho
      oligomers are the most active species. These and other results have enhanced our
      understanding of GPCR structure and function.

PMID- 16567092
TI  - 17 beta-estradiol activates PI3K/Akt signaling pathway by estrogen receptor (ER)
      dependent and ER-independent mechanisms in endometrial cancer cells.
AB  - Cellular response to estrogen is mediated both by estrogen receptor (ER) binding
      to estrogen response element (ERE) and by non-nuclear actions like activation of
      signal transducing pathways. The main aims are to study if PI3K/Akt signaling
      pathway can be activated by 17beta-estradiol (E2) via non-nuclear action and to
      investigate the relationship of the action of E2 and ER in endometrial cancer
      cells expressing with different status of ER. The levels of phosphorylated Akt
      (Ser473) (P-Akt) and total Akt were examined by western blot and Akt kinase
      activity was measured in cells after stimulation with 1 microM E2 at different
      time points. Inhibitory role of LY294002 on activation of Akt induced by E2 and
      its estrogen antagonist, ICI182780 were also tested. P-Akt/Akt was used as a
      measure of activation of Akt. We found that maximum P-Akt/Akt and Akt kinase
      activity took place at 30 min in Ishikawa cells and 15 min in HEC-1A cells and
      the activation persisted for at least 2 h after stimulation with 1 microM E2. The
      activation of Akt elicited gradually with increasing doses of E2. PI3K inhibitor,
      LY294002, stopped the activating Akt in a dose-dependent manner and 50 microM
      LY294002 completely blocked the activation of Akt induced by E2. ICI182780 could
      block the activation of PI3K/Akt in ER-positive Ishikawa cells but not in HEC-1A
      cells with poor-expressed ER. This study demonstrated that E2 is able to promptly
      activate PI3K/Akt signal pathway in Ishikawa cells in an ER-dependent manner and
      ER-independent in HEC-1A cells. Blockage of PI3K/Akt cascade may become a
      potential and effective way to control endometrial carcinoma, especially in ER
      negative cancers, which show no response to endocrinal therapy.

PMID- 16567093
TI  - Biomechanical features of gait waveform data associated with knee osteoarthritis:
      an application of principal component analysis.
AB  - This study compared the gait of 50 patients with end-stage knee osteoarthritis to
      a group of 63 age-matched asymptomatic control subjects. The analysis focused on
      three gait waveform measures that were selected based on previous literature
      demonstrating their relevance to knee osteoarthritis (OA): the knee flexion
      angle, flexion moment, and adduction moment. The objective was to determine the
      biomechanical features of these gait measures related to knee osteoarthritis.
      Principal component analysis was used as a data reduction tool, as well as a
      preliminary step for further analysis to determine gait pattern differences
      between the OA and the control groups. These further analyses included
      statistical hypothesis testing to detect group differences, and discriminant
      analysis to quantify overall group separation and to establish a hierarchy of
      discriminatory ability among the gait waveform features. The two groups were
      separated with a misclassification rate (estimated by cross-validation) of 8%.
      The discriminatory features of the gait waveforms were, in order of their
      discriminatory ability: the amplitude of the flexion moment, the range of motion
      of the flexion angle, the magnitude of the flexion moment during early stance,
      and the magnitude of the adduction moment during stance.

PMID- 16567094
TI  - Photodynamic therapy of cerebral glioma - a review. Part II - clinical studies.
AB  - Photodynamic therapy (PDT) is a binary treatment modality that has been used to
      treat malignant brain tumours for 25 years. The treatment involves the selective
      uptake of a photosensitizer (PS) by the tumour cells followed by irradiation of
      the tumour with light of the appropriate wavelength to excite and activate the PS
      resulting in selective tumour destruction and is a potentially valuable adjunct
      to surgical excision and other conventional therapies. PDT has undergone
      extensive laboratory studies and clinical trials with a variety of PS and tumour
      models. These are discussed with reference mainly to clinical studies involving
      the PDT of brain tumours.

PMID- 16567095
TI  - Tibial plateau fracture after anterior cruciate ligament reconstruction: Role of
      the interference screw resorption in the stress riser effect.
AB  - We report a case of tibial plateau fracture after previous anterior cruciate
      ligament (ACL) reconstruction using patellar tendon autograft and bioabsorbable
      screws 4 years previously. The fracture occurred through the tibial tunnel. The
      interference screw had undergone complete resorption and the tunnel widening had
      increased. The resorption of the interference screw did not simultaneously
      promote and foster the growth of surrounding bone tissue. Therefore, the area of
      reactive tissue left by the screw resorption in an enlarged bone tunnel may lead
      to vulnerability of the tibial plateau. Stress risers would occur following ACL
      reconstruction if either resorption is not complete or bony integration is not
      complete.

PMID- 16567096
TI  - Proficiency test for gamma spectroscopic analysis with a simulated fission
      product reference spectrum.
AB  - Within the proficiency test programme for the radionuclide laboratories
      supporting the verification of the Comprehensive Nuclear-Test-Ban Treaty, a
      simulated gamma spectrum with the characteristics of an atmospheric nuclear test
      was used as reference material. The spectrum was produced by the MCNP-based
      Virtual Gamma Spectroscopy Laboratory (VGSL), using analysis results of a
      historical measurement of nuclear weapons debris as input. The method was found
      suitable for a proficiency test assessing laboratories' gamma spectroscopic
      analysis.

PMID- 16567097
TI  - Development of gamma-ray emitting test sources for portal monitors.
AB  - A new set of gamma-ray emitting test sources was designed by the National
      Institute of Standards and Technology (NIST) for testing of radiation portal
      monitors for homeland security applications. This paper provides a description of
      the construction and characterization of these new sources that were designed and
      built to meet the American National Standard Institute (ANSI) N42.35-2004 and
      N42.38 standards' requirements.

PMID- 16567098
TI  - Monte Carlo calculations of spectra and interaction probabilities for photons in
      liquid scintillators for use in the standardization of radionuclides.
AB  - The probabilities for the interaction of photons, Pint, in three different liquid
      scintillators (toluene, Ultima Gold, and Hionic Fluor) were calculated as a
      function of energy for three different geometries using the Monte Carlo codes
      PENELOPE and EGSnrcMP. The agreement in Pint values between the two codes in all
      of the geometries and scintillators for energies above 100 keV was within +/
      0.5%. The agreement was better than +/-4% for energies between 20 and 100 keV. No
      substantive differences in the normalized absorbed energy spectra were observed
      for initial photon energies in the range of 20-1000 keV. The influence of
      scintillator composition on the simulation results was investigated in the
      context of a possible conflict in the published composition data for Hionic
      Fluor. A difference in interaction probability of about 27% was observed at 20
      keV when an alternate composition having lower amounts of S and P is used. At 100
      keV, the differences were within the calculational uncertainties.

PMID- 16567099
TI  - Left ventricular geometry reconstruction in ischemic cardiomyopathy patients with
      predominantly hypokinetic left ventricle.
AB  - OBJECTIVE: The effectiveness of the left ventricle (LV) geometry reconstruction
      (Dor procedure) as the method of surgical treatment of LV post-infarction
      aneurysm and large dilated myocardial scars is well established. The efficacy of
      LV restoration in cases of globally dilated hypofunctional LV, containing the
      same spherical architecture as scarred, remains questionable. METHODS: The
      results of LV geometry reconstruction in small population of patients with
      ischemic dilated cardiomyopathy (IDCMP) and predominantly hypokinetic LV are
      described in 14 patients of that underwent LV rebuilding into a conical
      architecture. Surgical procedures included LV geometry reconstruction with the
      synthetic patch, narrowing of widened dimensions between papillary muscles,
      coronary artery bypass grafting (CABG) and, in several cases, mitral and
      tricuspid valves annuloplasty. RESULTS: Initial mean end-diastolic and end
      systolic volumes indexes were 177 and 112 ml/m2, respectively, mean LV ejection
      fraction (EF) of 32.9%. The analysis of immediate and mid-term (1 and 4 years)
      results proved that LV reconstruction markedly decreased LV volumes and increased
      LVEF an average of +12% above resting values with significant improvement in
      clinical status. CONCLUSIONS: A rebuilding procedure for the scarred heart is now
      introduced to be used in ischemic patients with dilated ischemic cardiomyopathy
      without significant scar. Preliminary structural and physiological results imply
      that creating an elliptical form has potential importance during LV
      reconstruction of very sick patients with IDCMP without discrete scar.

PMID- 16567100
TI  - Stonehenge and the heart: similar construction.

PMID- 16567101
TI  - Tenth RESTORE Group Meeting: overview.

PMID- 16567102
TI  - The helical ventricular myocardial band of Torrent-Guasp: potential implications
      in congenital heart defects.
AB  - The new concepts of cardiac anatomy and physiology, based on the observations
      made by Francisco Torrent-Guasp's discovery of the helical ventricular myocardial
      band, can be useful in the context of the surgical strategies currently used to
      manage patients with congenital heart defects. The potential impact of the
      Torrent-Guasp's Heart on congenital heart defects have been analyzed in the
      following settings: ventriculo-arterial discordance (transposition of the great
      arteries), double (atrio-ventricular and ventriculo-arterial) discordance
      (congenitally corrected transposition of the great arteries), Ebstein's anomaly,
      pulmonary valve regurgitation after repair of tetralogy of Fallot, Ross
      operation, and complex intra-ventricular malformations. The functional
      interaction of right and left ventricles occurs not only through their
      arrangements in series but also thanks to the structural spiral features. Changes
      in size and function of either ventricle may influence the performance of the
      other ventricle. The variety and complexity of congenital heart defects make the
      recognition of the relationship between form and function a vital component,
      especially when compared to acquired disease. The new concepts of cardiac anatomy
      and function proposed by Francisco Torrent-Guasp, based on his observations,
      should stimulate further investigations of alternative surgical strategies by
      individuals involved with the management of patients with congenital heart
      defects.

PMID- 16567103
TI  - The ventricular septum: the lion of right ventricular function, and its impact on
      right ventricular restoration.
AB  - OBJECTIVE: To evaluate the structure-function relationships of the right
      ventricle (RV) and septum and determine if the helical ventricular band model
      would define fiber orientation for maximal force response. Implications were made
      for right ventricular function. METHODS: The right ventricular free wall and
      biventricular septum were studied by inserting sonomicrometer crystals at
      different angulations to determine the maximum response of fiber shortening.
      These reactions were compared to the lateral left ventricular (LV) wall and
      further tested by use of positive and negative inotropic drug infusions. RESULTS:
      The maximum contraction of the free wall was achieved by placing crystals in the
      transverse orientation angulations, whereas oblique orientation allowed the
      maximal septal response. Fiber orientation angulation was the same for the LV
      free wall and septum. These angulations correlate with the MRI-related twisting
      actions of septal motion needed for ejection and suction for rapid filling. These
      findings have important impact, because they imply that the septum is 'lion of
      right ventricular function,' since septal twisting is essential when pulmonary
      vascular resistance is increased. The incidence of postoperative right heart
      failure due to septal dyssyncrony, with loss of septal twisting action from
      inadequate myocardial protection, is explored relative to RV free wall and septum
      function. Furthermore, early studies of right ventricular restoration in patients
      with RV dysplasia and RV failure after chronic pulmonary insufficiency following
      repair of Tetralogy of Fallot are described, with predominant attention directed
      toward rebuilding normal septal architecture and function. CONCLUSIONS: This
      experimental and clinical overview indicates that the septum is 'the lion of
      right ventricular function,' and implies that the use of this knowledge can
      become an important guideline for planning novel surgical geometric interventions
      after RV failure.

PMID- 16567104
TI  - Structure/function interface with sequential shortening of basal and apical
      components of the myocardial band.
AB  - OBJECTIVE: To study the sequential shortening of Torrent-Guasp's 'rope-heart
      model' of the muscular band, and analyze the structure-function relationship of
      basal loop wrapping the outer right and left ventricles, around the inner helical
      apical loop containing reciprocal descending and ascending spiral segments.
      METHODS: In 24 pigs (27-82 kg), temporal shortening by sonomicrometer crystals
      was recorded. The ECG evaluated rhythm, and Millar pressure transducers measured
      intraventricular pressure and dP/dt. RESULTS: The predominant shortening sequence
      proceeded from right to left in basal loop, then down the descending and up the
      ascending apical loop segments. In muscle surrounded by the basal loop,
      epicardial muscle predominantly shortened before endocardial muscle. Crystal
      location defined underlying contractile trajectory; transverse in basal versus
      oblique in apical loop, subendocardial in descending and subepicardial in
      ascending segments. Mean shortening fraction average 18+/-3%, with endocardial
      exceeding epicardial shortening by 5+/-1%. Ascending segment crystal displacement
      followed descending shortening by 82+/-23 ms, and finished 92+/-33 ms after
      descending shortening stops, causing active systolic shortening to suction venous
      return; isovolumetric relaxation was absent. CONCLUSIONS: Shortening sequence
      followed the rope-like myocardial band model to contradict traditional thinking.
      Epicardial muscle shortened before endocardial papillary muscle despite early
      endocardial activation, and suction filling follows active systolic unopposed
      ascending segment shortening during the 'isovolumetric relaxation' phase.

PMID- 16567105
TI  - Active myocyte shortening during the 'isovolumetric relaxation' phase of diastole
      is responsible for ventricular suction; 'systolic ventricular filling'.
AB  - OBJECTIVE: To study the 'isovolumetric relaxation' phase of rapid ventricular
      filling by analysis of the shortening of cardiac muscle in the endocardial and
      epicardial segments of the left ventricle in the dual helical model of the
      ventricular band, described by Torrent-Guasp. METHODS: In 10 pigs (27-82 kg),
      temporal shortening by sonomicrometer crystals was recorded while recording ECG,
      and measuring intraventricular pressure and dP/dt with Millar pressure
      transducers. RESULTS: The following sequence was observed; shortening began in
      descending or endocardial segment, and 82+/-23 ms later it was initiated in the
      epicardial or ascending segment of the band. The descending segment stops
      shortening during the rapid filling phase of fast descent of ventricular
      pressure, but the ascending segment shortening continues for 92+/-33 ms, so that
      active shortening continues during the period of isovolumetric relaxation. During
      the rapid filling phase, dopamine decreased the interval between completion of
      endocardial and termination of epicardial contraction from 92+/-20 to 33+/-8 ms.
      Conversely propranolol delayed the start of epicardial shortening from 82+/-23 to
      121+/-20 ms, and prolonged the duration of endocardial contraction, causing a
      closer (21+/-5 ms vs 92+/-20 ms) interval between termination of contraction of
      endocardial and epicardial fibers. The resultant slope of the rapid descent of
      the left ventricular pressure curve became prolonged. CONCLUSIONS: These time
      sequences show that ongoing unopposed ascending segment shortening occurs during
      the phase of rapid fall of ventricular pressure. These active shortening phases
      respond to positive and negative inotropic stimulation, and indicate the classic
      concept of 'isovolumetric relaxation', IVR, must be reconsidered, and the new
      term 'isovolumetric contraction', IVC, or systolic ventricular filing may be
      used.

PMID- 16567106
TI  - A new concept of ventricular restoration for nonischemic dilated cardiomyopathy.
AB  - OBJECTIVE: Left ventricular restoration is used to treat patients with chronic
      progressive heart failure caused by nonischemic dilated cardiomyopathy. This
      study addresses the use of site selection to determine either lateral wall or
      septal exclusion. METHODS: Evolution of intraoperative echocardiography to define
      the site of poorest contraction and use of multiple biopsies to show the
      nonhomogeneous nature of damage are reviewed. To address the heterogeneity of
      extent of fibrosis in nonischemic cardiomyopathy, target selection was used to
      determine the mode of left ventriculoplasty. Either the lateral wall was excluded
      by partial left ventriculectomy (PLV) or septal anterior ventricular exclusion
      (SAVE or Pacopexy) was employed if the septum was primarily diseased. Surgical
      results in 107 high-risk (43% NYHA (New York Heart Association) class III and 57%
      class IV) patients with idiopathic dilated cardiomyopathy over the past 9 years
      are reviewed. RESULTS: Overall hospital mortality was 7.1% in 84 elective
      operations and 60.9% in 23 emergency operations, and fell from 42.8% (6 of 14) to
      15.0% (14 of 93), when site selection for the area of left ventricular excision
      or exclusion was determined by the intraoperative echocardiography test. The
      SAVE/Pacopexy procedure was performed in 36 patients with 62.2% 5-year survival
      rate. For the entire cohort of PLV and SAVE/Pacopexy population, overall ejection
      fraction increased from 20 to 31%, and NYHA class improved from 3.6 to 1.8. The 1
      , 5-, and 7-year survival rates were 66.9, 46.0, and 36.2%, respectively. In
      patients having the operation before inotropic dependent, the survival rate was
      78.1, 58.0, and 50.2%, respectively. CONCLUSIONS: Left ventriculoplasty is
      effective for patients with idiopathic dilated cardiomyopathy with heart failure
      by proper patient selection, appropriate timing of the operation, and choice of
      the surgical procedure (exclusion site selection).

PMID- 16567107
TI  - The myocardium and its fibrous matrix working in concert as a spatially netted
      mesh: a critical review of the purported tertiary structure of the ventricular
      mass.
AB  - With the increasing interest now paid to volume reduction surgery, in which the
      cardiac surgeon is required to resect the ventricular myocardium to an extent
      unenvisaged in the previous century, it is imperative that we develop as precise
      knowledge as is possible of the basic structure of the ventricular myocardial
      mass and its functional correlates. This is the most important in the light of
      the adoption by some cardiac surgeons of an unvalidated model which hypothesises
      that the entire myocardial mass can be unravelled to produce one continuous band.
      It is our opinion that this model, and the phylogenetic and functional correlates
      derived from it, is incompatible with current concepts of cardiac structure and
      cardiodynamics. Furthermore, the proponents of the continuous myocardial band
      have made no effort to demonstrate perceived deficiencies with current concepts,
      nor have they performed any histological studies to validate their model.
      Clinical results using modifications of radius reduction surgery based on the
      concept of the continuous myocardial band show that the procedure essentially
      becomes ineffective. As we show in this review, if we understand the situation
      correctly, it was the erstwhile intention of the promoters of the continuous band
      to elucidate the basic mechanism of diastolic ventricular dilation. Their
      attempts, however, are doomed to failure, as is any attempt to conceptualise the
      myocardial mass on the basis of a tertiary structure, because of the underlying
      three-dimensional netting of the myocardial aggregates and the supporting fibrous
      tissue to form the myocardial syncytium. Thus, the ventricular myocardium is
      arranged in the form of a modified blood vessel rather than a skeletal muscle. If
      an analogy is required with skeletal muscle, then the ventricular myocardium
      possesses the freedom of motion, and the ability for shaping and conformational
      self-controlling that is better seen in the tongue. It is part of this ability
      that contributes to the rapid end-systolic ventricular dilation. Histologic
      investigations reveal that the fibrous content of the three-dimensional mesh is
      relatively inhomogeneous through the ventricular walls, particularly when the
      myocardium is diseased. The regional capacity to control systolic mural
      thickening, therefore, varies throughout the walls of the ventricular components.
      The existence of the spatially netted structure of the ventricular mass,
      therefore, must invalidate any attempt to conceptualise the ventricular
      myocardium as a tertiary arrangement of individual myocardial bands or tracts.

PMID- 16567108
TI  - Myocardial protection during surgical ventricular restoration.
AB  - OBJECTIVE: Ventricular restoration is a novel procedure for treating congestive
      heart failure (CHF). The two important features include a technically correct
      procedure and adequate myocardial protection. The two protective techniques
      include conventional cardioplegia and the beating heart. METHODS: This report
      reviews a RESTORE clinical registry and summarizes background experimental work
      related to myocardial protection in failing dilated hearts. RESULTS: The RESTORE
      registry is reported, where protection is 55% with cardioplegia and 45% with
      beating heart. The beating method was used more frequently in patients with
      ejection fraction <30%, end systolic volume 80 ml/m2, NYHA class >III/IV. Overall
      survival results favored cardioplegia except for the first 30 days, but after
      matching patients on age, ejection fraction (EF) and NYHA the beating results and
      cardioplegic results were comparable. Experimental work evaluated the safety of
      the beating method in failing dilated ventricles under acute conditions.
      Supplemental coronary perfusion studies in chronically dilated hearts after
      tachycardia induced cardiomyopathy were analyzed to show that (a) there was
      vascular remodeling (less flow at the same pressure in failing hearts with
      cardioplegic, but not beating delivery; (b) in the open state (used during
      restoration) subendocardial flow increased in the beating heart, and fell after
      cardioplegia. These studies were done without ischemia. CONCLUSIONS: Cardioplegic
      delivery for protection is 'time dependent' (needing ischemic intervals) while
      beating nourishment is 'procedure dependent,' as continuous perfusion is provided
      throughout the procedure is suggested. The importance of maintaining high
      perfusion pressure is emphasized.

PMID- 16567109
TI  - Septal anterior ventricular exclusion operation (Pacopexy) for ischemic dilated
      cardiomyopathy: treat form not disease.
AB  - OBJECTIVE: Restoration of left ventricle size and shape is an effective surgical
      procedure in patients with dilated cardiomyopathy. This report defines early and
      intermediate results following the reshaping of the left ventricle from spherical
      to ellipsoid configuration in patients with ischemic cardiomyopathy, employing a
      technique for LV restoration (LVR) that uses form rather than disease as the
      endpoint for oblique patch placement. METHODS: Between 1998 and 2004, a cohort of
      83 patients with dilated ischemic cardiomyopathy underwent an operation to
      reshape the left ventricle. In 54 patients the Dor procedure was done, and 29
      underwent the septal anterior ventricular exclusion (SAVE) procedure to emphasize
      the elliptical shape, whereby patch placement followed an oblique trajectory
      between the LV apex and septum below the aortic valve. Ventricular form, rather
      than the disease scar marked the suture placement site endpoint to create an
      ellipse. The mean age was 58+/-27, but SAVE patients had larger end systolic
      volume index (135+/-38 vs 95+/-25). Overall preoperative NYHA functional class
      III was in 69% and IV in 31 patients, but more SAVE patients were in class IV
      (38% vs 28%). The procedures were elective in 72 and emergent in 11, with similar
      entry criteria for each procedure. RESULTS: In combination with LVR operation,
      mitral surgery was performed in 49/83 and tricuspid annuloplasty in 23/83
      patients, but these procedures were more common after SAVE (59% vs 44% and 45% vs
      19%, respectively), because of larger LV volumes in SAVE patients; 2.8+/-1.3
      coronary artery bypass grafts were used. Perioperative use of IABP or LVAD was 15
      and 1, respectively in 83 patients. Hospital death was in 1/11 or 9% after
      emergent operations and 3/72 or 4% in elective procedures, with no difference
      between groups. After discharge from the hospital, NYHA class improved to class I
      or II in 57 patients, class III/IV in 14 patients, with 10 late deaths. The 5
      year survival rate after the elective operation was 80.3% in SAVE and with
      elective operation and 77.4% in the Dor procedure. CONCLUSION: The SAVE or
      Pacopexy technique is easy to reshape the dilated left ventricle from spherical
      to ellipsoid form after the LVR, and the resultant improved configuration may
      contribute to the overall results for patients with ischemic dilated
      cardiomyopathy.

PMID- 16567110
TI  - CXCL5 gene polymorphisms are related to systemic concentrations and leukocyte
      production of epithelial neutrophil-activating peptide (ENA-78).
AB  - Data exist linking elevated epithelial neutrophil activating peptide (ENA-78)
      concentrations with myriad inflammatory conditions. ENA-78 is encoded by the
      CXCL5 gene which has recently been shown to be polymorphic in nature (rs352046
      and rs425535). No functional data on these polymorphisms exist. We investigated
      whether CXCL5 polymorphisms are associated with differences in plasma ENA-78
      concentrations or leukocyte production of ENA-78 from cultured leukocytes in
      relatively healthy adults. We genotyped 114 adults for the above polymorphisms.
      Variant alleles at both loci were highly linked (D'=1, r2=0.94). The rs352046
      variant allele was associated with significantly higher ENA-78 plasma
      concentrations. A genotype effect was also demonstrated for this polymorphism and
      leukocyte production of ENA-78. Both polymorphisms were predicted to have
      functional consequences by in silico analyses, with the rs352046 polymorphism
      found to occur at a transcription factor binding site for myeloid zinc finger
      proteins and the rs425535 polymorphism found to be located in an exon splicing
      enhancer site. Our findings add to the strength of CXCL5 as candidate gene in
      future disease-gene and pharmacogenetic association studies.

PMID- 16567111
TI  - Effect of commonly used vehicles on gastrointestinal, renal, and liver function
      in rats.
AB  - INTRODUCTION: Solubility is often a limiting factor when testing new compounds in
      animal experiments. Various solubilizing agents may be used, but each have their
      own pharmacological effects. We investigated the effects of selected vehicles
      having different chemical characteristics on gastrointestinal, renal, and liver
      function. METHODS: Rats were treated orally, intravenously or intraperitoneally
      and gastric emptying, intestinal transit, renal, and liver function were
      investigated. RESULTS: Gastrointestinal motility was influenced by
      hydroxyethylcellulose, hydroxypropyl-beta-cyclodextrin (HPbetaCD), HPgammaCD,
      DMSO, polyethylene glycol 400 (PEG 400), fat emulsion, and the corresponding
      emulsifier. Liver function was affected by HPbetaCD, HPgammaCD, DMSO, PEG 400,
      Polysorbate 80, Cremophor RH 40, and fat emulsion. An increase in liver enzymes
      was observed after PEG 400 and Polysorbate 80. DMSO interfered with clinical
      chemistry measurements in serum. Urinary function was modified by HPgammaCD,
      DMSO, PEG 400, and Polysorbate 80, while enhanced urine enzyme excretion was
      observed after HPbetaCD, HPgammaCD, DMSO, PEG 400, and Polysorbate 80.
      DISCUSSION: Most of the investigated vehicles changed gastrointestinal, renal,
      and/or liver parameters after application of a certain threshold dose for each
      assay. No "best" vehicle could be identified that may be used in each test
      system. Thus, vehicles must be selected not only on their chemical
      characteristics but also on their potential pharmacological activity in a given
      test system.

PMID- 16567112
TI  - Applicability of reverse microdialysis in pharmacological and toxicological
      studies.
AB  - A recent application of microdialysis is the introduction of a substance into the
      extracellular space via the microdialysis probe. The inclusion of a higher amount
      of a drug in the perfusate allows the drug to diffuse through the microdialysis
      membrane to the tissue. This technique, actually called as reverse microdialysis,
      not only allows the local administration of a substance but also permits the
      simultaneous sampling of the extracellular levels of endogenous compounds. Local
      effects of exogenous compounds have been studied in the central nervous system,
      hepatic tissue, dermis, heart and corpora luteae of experimental animals by means
      of reverse microdialysis. In central nervous studies, reverse microdialysis has
      been extensively used for the study of the effects on neurotransmission at
      different central nuclei of diverse pharmacological and toxicological agents,
      such as antidepressants, antipsychotics, antiparkinsonians, hallucinogens, drugs
      of abuse and experimental drugs. In the clinical setting, reverse microdialysis
      has been used for the study of local effects of drugs in the adipose tissue,
      skeletal muscle and dermis. The aim of this review is to describe the principles
      of the reverse microdialysis, to compare the technique with other available
      methods and finally to describe the applicability of reverse microdialysis in the
      study of drugs properties both in basic and clinical research.

PMID- 16567113
TI  - A one-step approach to the analysis of the QT interval in conscious telemetrized
      dogs.
AB  - INTRODUCTION: To account for heart rate-induced changes in the QT interval,
      correction formulas are generally applied to normalize the QT interval for heart
      rate. None of these formulas is entirely accurate because correction or
      normalization of any parameter in biology may introduce an additional source of
      variation in estimating the parameter. In this article, a one-step approach for
      the statistical analysis of the QT interval was proposed based on modeling the
      functional relationship between the QT interval and heart rate. METHODS: The QT
      HR relationship was incorporated into the statistical analysis to provide a model
      based correction. This was accomplished by including HR as a covariate in the QT
      interval analysis. The approach was demonstrated using data generated from Lilly
      Research Laboratories. We compared the false positive rate and statistical power
      of QT, QTcF, and the proposed one-step method. RESULTS: We found the one-step
      method demonstrated the greatest sensitivity in detecting a QT interval change
      without an increase in the false positive rate. It was shown that the one-step QT
      analysis could detect a 5%-6% increment of the QT interval. This is approximately
      equivalent to an increase of 11-13 ms in QT interval in beagle dogs. DISCUSSION:
      Several advantages and unique features of the one-step method are discussed.
      These include evaluating treatment effect on QT without applying a heart rate
      correction formula and estimating QT difference flexibly at any selected heart
      rate. In addition to the linear QT-HR relationship, other functional
      relationships can be easily implemented to this approach.

PMID- 16567114
TI  - EEG departments in Great Britain: a survey of practice.
AB  - OBJECTIVE: Guidelines have been published recently on when an
      electroencephalogram (EEG) should be undertaken and the expected waiting time for
      a routine EEG, but have not included recommendations on how an EEG should be
      undertaken or who should undertake and report EEGs. The purpose of this survey
      was to obtain background information on the composition and practice of EEG
      departments throughout Great Britain that might form the basis for additional
      recommendations and guidelines. METHODS: A postal questionnaire was sent to all
      EEG departments in Great Britain in 2001/2002; non-responders were sent a further
      copy of the questionnaire. RESULTS: Fifty-two departments responded, representing
      a response rate of 48%. The reasons for this relatively poor response rate are
      not known. Findings indicated that a single doctor reported EEGs in 44% of all
      departments. The speciality of doctor reporting EEGs included neurophysiologists
      (59%), neurologists (22%), paediatric neurologists (PNs) (13%), psychiatrists
      (5%) and one general practitioner (GP). EEG recordists from 28 departments (54%)
      and medical staff in 21 departments (40%) stated that they had not received any
      formal training in, respectively, undertaking and reporting EEGs in children. In
      29 departments (55%), medical staff report EEGs independently from the
      recordists. Fourteen departments (27%) undertake less than 500 EEGs per year. Ten
      of the 42 departments providing a paediatric service perform less than 100
      paediatric EEGs per year. Eighteen (35%) and eight (15%) units have a waiting
      time of 2-4 and over 12 weeks, respectively, for a routine EEG. CONCLUSIONS: This
      survey has identified a range of practice and operational procedures in 52 EEG
      departments throughout Great Britain. These findings may have implications on the
      investigation and management of people with non-epileptic seizures and epilepsy.

PMID- 16567115
TI  - A modified technique of transperitoneal direct approach for totally laparoscopic
      aortoiliac surgery.
AB  - OBJECTIVE: To present our modification of the transperitoneal direct approach
      (TDA) for totally laparoscopic aortoiliac surgery. METHODS AND RESULTS: From
      September 2003 to August 2005 a total of 52 patients underwent laparoscopic
      operations for aortoiliac disease (50 aortoiliac occlusive disease; two abdominal
      aortic aneurysm). The modified TDA was used in 20 patients. CONCLUSION: The main
      advantage of TDA is reduced dissection of the aorta and pelvic arteries resulting
      in lowered blood loss and lymphatic injury.

PMID- 16567116
TI  - Improvement of quality of life six months after infrageniculate bypass surgery:
      diabetic patients benefit less than non-diabetic patients.
AB  - OBJECTIVES: The aim of the study was to assess the change in health related
      quality of life (HRQoL) after infrageniculate bypass grafting in patients with
      critical limb ischaemia (CLI). DESIGN: Observational, prospective clinical study.
      MATERIALS AND METHODS: In total, 86 patients (72% male; age 71 (IQR, 64-78)
      years) undergoing infrageniculate bypass grafting for limb salvage were assessed
      by the short form (SF)-36 questionnaire before and 6 months after surgery. In
      subgroup analysis, the influence of diabetes mellitus, age, gender, and stage of
      peripheral arterial occlusive disease on HRQoL-outcome were assessed. RESULTS:
      Following revascularization HRQoL significantly improved in all eight dimensions
      of the SF-36. While baseline HRQoL-values of diabetic and non-diabetic patients
      did not differ significantly, postoperative improvement was significantly less in
      the diabetes group. CONCLUSIONS: An aggressive approach towards infrageniculate
      bypass surgery for limb salvage is justified by quality of life improvement.
      However, this improvement tends to be less in patients with diabetes mellitus.

PMID- 16567117
TI  - The significance of reduced respiratory chain enzyme activities: clinical,
      biochemical and radiological associations.
AB  - BACKGROUND: Mitochondrial diseases are an important group of neurometabolic
      disorders in children with varied clinical presentations and diagnosis that can
      be difficult to confirm. AIM: To report the significance of reduced respiratory
      chain enzyme (RCE) activity in muscle biopsy samples from children. METHODS:
      Retrospective odds ratio was used to compare clinical and biochemical features,
      DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without
      reduced RCE activity. RESULTS: Children with reduced RCE activity were
      significantly more likely to have consanguineous parents, to present with acute
      encephalopathy and lactic acidaemia and/or within the first year of life; to have
      an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the
      basal ganglia. There were positive associations with a maternal family history of
      possible mitochondrial cytopathy; a presentation with failure to thrive and
      lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and
      with an abnormal allopurinol loading test. There was no association with
      ophthalmic abnormalities, deafness, epilepsy or myopathy. CONCLUSION: The
      association of these clinical, biochemical and radiological features with reduced
      RCE activity suggests a possible causative link.

PMID- 16567118
TI  - Fatal outcome following foetal cerebellar haemorrhage associated with placental
      thrombosis.
AB  - Cerebellar haemorrhage is a rare prenatal event. Possible aetiologies for foetal
      intracranial haemorrhage include: trauma, asphyxia, infection, vascular defects,
      blood dyscrasias, ingestion of drugs and alloimmune and isoimmune
      thrombocytopenia. We report the ultrasonographic diagnosis of a cerebellar
      haematoma at 21 weeks of gestation. The foetus succumbed at 33 weeks of gestation
      following rupture of a subcapsular liver haematoma. An autopsy demonstrated a
      placental foetal thrombotic vasculopathy and thrombi in the chorionic vessels. We
      assume that hypercoagulability was responsible for the multiple infarcts in the
      foetus with haemorrhagic transformation in the cerebellum and liver. The
      differential diagnosis of foetal cerebellar haemorrhage includes maternal
      hypercoagulability; in this case multiple haemorrhagic/ischaemic events may be
      encountered during the pregnancy. A thorough investigation to elucidate the
      aetiology is pertinent in every case of foetal cerebellar haemorrhage in order to
      enable accurate counselling and correct management.

PMID- 16567119
TI  - Retention of structural and functional polarity in cultured skate hepatocytes
      undergoing in vitro morphogenesis.
AB  - The present study characterized a primary culture model of hepatocytes isolated
      from the little skate, Leucoraja erinacea, that maintain remarkable structural
      and functional polarity over 7 days in culture. Skate hepatocytes were isolated
      as clusters of 3-20 hepatocytes surrounding a bile canaliculus, rather than as
      single cells. Trypan blue and propidium iodide exclusion was found to be >98%,
      and the cells maintained high intracellular concentrations of K+, ATP, and
      reduced glutathione (GSH), and high ratios of ATP/ADP and GSH/GSSG. Glutathione S
      transferase activity remained constant, whereas cytochrome P450 activity declined
      to 16% of initial levels after 7 days. Quantitative RT-PCR analysis revealed that
      the mRNA levels of several genes remained constant over the 7-day period, whereas
      Bsep, the canalicular bile salt export pump, levels declined slowly to 30% of
      initial values. In the presence of dexamethasone, the cells underwent a
      morphogenesis in which the clusters reannealed into a three-dimensional network
      of chords. During this morphogenesis, skate hepatocytes clusters maintained a
      polarized distribution of actin filaments and microtubules, as well as apical and
      basolateral membrane domains. Polarity of membrane transport systems was
      confirmed both morphologically, using antibodies raised against Bsep and Mrp2,
      the canalicular multispecific organic anion transporter, and functionally, by
      monitoring secretion of the fluorescent organic anions NBD-taurocholate, a Bsep
      substrate, and fluorescein-methotrexate, an Mrp2 substrate, into the bile
      canalicular spaces. Overall, the results indicate that in contrast with mammalian
      hepatocytes, isolated skate hepatocyte clusters retain polarity in culture, and
      provide an excellent system for investigating long-term effects of drugs and
      xenobiotics on hepatobiliary functions, and for studying in vitro morphogenesis.

PMID- 16567120
TI  - An ontological approach to support the description of nursing practice in Japan
      with the ICNP.
AB  - BACKGROUND: With increasing computerization of nursing records in Japan,
      standardization of nursing terminology is becoming imperative. Although some
      efforts have been made to formalize description of nursing practice in Japan with
      the International Classification of Nursing Practice (ICNP), lack of effective
      description tools has impacted negatively on the initiatives. PURPOSE: To develop
      and evaluate an ontological approach that could be used to facilitate the
      description of nursing practice in Japan with the ICNP. METHODOLOGY: An ontology
      based support system was developed using Protege-2000, mainly by the following
      three steps: (1) representing a standard classification of nursing practice (the
      Nursing Master) in Japan; (2) representing a Japanese version of the ICNP; (3)
      designing an ontology-based framework. A heuristic matching algorithm was
      developed to automatically match the action labels in the Nursing Master with the
      terms of the eight axes of the ICNP Nursing Actions Classification. A preliminary
      evaluation was performed to examine the usefulness of the system. RESULTS: High
      hit rate was shown on the ICNP axes ActionType, Target, and Location. The
      evaluation indicated that 51.7+/-5.8% (mean+/-S.D.) of the action labels with
      only one action type were properly matched, and that in 80+/-4% (mean+/-S.D.) of
      action labels with more than one action type, at least one valid action type was
      matched correctly. CONCLUSION: The ontology-based approach using a frame-based
      knowledge representation system (e.g., Protege-2000) is useful for supporting the
      formal description of nursing practice in Japan with the ICNP.

PMID- 16567121
TI  - The impact of computerised physician order entry systems on pathology services: a
      systematic review.
AB  - PURPOSE: Computerised physician order entry (CPOE) systems hold the promise of
      significant improvements to health care delivery and patient care. The
      implementation of such systems is costly and complex. The purpose of this paper
      is to review current evidence of the impact of CPOE on hospital pathology
      services. METHODS: This paper presents a review of the literature (1990-August
      2004) about CPOE systems and identifies indicators for measuring the impact of
      CPOE on pathology services. RESULTS: Nineteen studies which contained some form
      of 'control' group, were identified. They featured a variety of designs including
      randomised controlled trials, quasi-experimental and before and after studies. We
      categorised these into three groups: studies comparing pathology CPOE systems
      (with no decision support) to paper systems; pathology CPOE systems (with
      decision support) to paper systems; and pathology CPOE systems with specific
      pathology features compared to systems without those features. We identified 10
      areas of impact assessment and 39 indicators used to measure the impact of CPOE
      on different stages of the pathology test ordering and reporting process.
      CONCLUSION: We conclude that while some data suggest that CPOE systems are
      beneficial for clinical and laboratory work processes, these data are limited,
      and further research is needed. Few data are available regarding the impact of
      CPOE on patient outcomes.

PMID- 16567122
TI  - Altered expression of alkaline phosphatase (ALP) in the liver of primary biliary
      cirrhosis (PBC) patients.
AB  - Serum alkaline phosphatase (ALP) is a representative marker of cholestasis, in
      diseases such as primary biliary cirrhosis (PBC). However, the hepatic
      localization of ALP in patients with cholestatic liver diseases has not been
      fully clarified. Accordingly, we studied the expression of ALP in the liver of
      PBC, chronic hepatitis C and controls. By immunohistochemistry, in the liver
      tissue of controls and chronic hepatitis C patients, ALP was found to be
      localized in the canalicular membrane of hepatocytes and the apical area of the
      cytoplasm of bile duct epithelial cells. In PBC, ALP was localized in both the
      canalicular and baso-lateral membranes of hepatocytes and in the whole cytoplasm
      of the remaining bile duct epithelial cells. The expression of ALP in liver
      tissues evaluated by Western blotting was increased to 3.6-fold in PBC compared
      with that in the controls and chronic hepatitis C patients, while the expression
      of mRNA of ALP evaluated by RT-PCR was increased to 7.0-fold in PBC compared with
      that in the controls and chronic hepatitis C patients. The present study is the
      first study to reveal altered localization and increased expression of ALP which
      may result in the elevation of serum ALP in PBC.

PMID- 16567123
TI  - G protein-mediated signal transduction is affected in primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by
      severe intraepatic cholestasis. Pruritus often occurs during the course of the
      illness. We designed a study aimed at assessing whether pruritus is associated
      with dysfunction of signal transduction. Seventeen female patients affected by
      PBC were enrolled into the study and divided in two groups according to severity
      of liver disease. Leukocytes were isolated from peripheral blood and Gi, Go and
      Gs protein expressions were evaluated by western blotting, while G protein
      function was assessed by measuring cyclic adenosine phosphate formation. The
      expression of all types of G proteins was increased in leukocytes of PBC
      patients. The basal adenylate activity was significally higher than control in
      patients with less severe liver disease, while it was lower than normal in those
      with severe liver disease. Incubation of patient leukocytes with guanosine
      triphosphate-gamma-S and Gs protein activators failed to enhance cAMP production,
      while N-formyl-met-leu-phe was more effective in reducing cAMP production. The
      expression of all G proteins was non-selectively increased in PBC leukocytes,
      while adenylate cyclase activity was significantly modified. However, the
      observed changes in G proteins expression and in adenylate cyclase activity are
      not related to the presence of pruritus.

PMID- 16567124
TI  - PIKE GTPase-mediated nuclear signalings promote cell survival.
AB  - The nuclear GTPase PIKE (PI 3-kinase Enhancer) binds PI 3-kinase and enhances it
      lipid kinase activity. PIKE predominantly distributes in the brain, and nerve
      growth factor stimulation triggers PIKE activation by provoking nuclear
      translocation of PLC-gamma1, which acts as a physiologic guanine nucleotide
      exchange factor (GEF) for PIKE through its SH3 domain. PIKE contains GTPase and
      ArfGAP domains, which are separated by a PH domain. C-terminal ArfGAP domain
      activates its internal GTPase activity, and this process is regulated by the
      interaction between phosphatidylinositols and PH domain. PI 3-kinase occurs in
      the nuclei of a broad range of cell types, and various stimuli elicit its nuclear
      translocation. The nuclei from NGF-treated PC12 cells are resistant to DNA
      fragmentation initiated by activated cell-free apoptosome, for which PIKE/nuclear
      PI 3-kinase signaling through nuclear PI(3,4,5)P(3) and Akt plays an essential
      role. As a nuclear receptor for PI(3,4,5)P(3,) B23 binds to PI(3,4,5)P(3) in an
      NGF-dependent way. The PI(3,4,5)P(3)/B23 complex inhibits DNA fragmentation
      activity of CAD. Nuclear Akt regulation of apoptosis is dependent on its
      phosphorylation of key substrates in the nucleus, but the identities of these
      substrates are unknown. Identification of its nuclear substrates will further our
      understanding of the physiological roles of nuclear PI 3-kinase/Akt signaling.

PMID- 16567125
TI  - Formation of conjugated linoleic acid metabolites in human vascular endothelial
      cells.
AB  - Conjugated linoleic acids (CLAs) are bioactive lipid compounds showing anti
      atherogenic actions in cell culture experiments and animal models of
      atherosclerosis without exact knowledge about the underlying mechanisms. CLAs
      were recently reported to be further metabolized to bioactive conjugated
      metabolites indicating that these metabolites are possibly involved in mediating
      the anti-atherogenic actions of CLA. Regarding the lack of information with
      respect to the formation of CLA metabolites in the vascular endothelium, which is
      strongly involved in the process of atherosclerosis, the present study aimed to
      explore the potential formation of CLA metabolites in vascular endothelial cells.
      The results from the present study show for the first time that the CLA isomers
      cis-9, trans-11 CLA and trans-10, cis-12 CLA are metabolized within endothelial
      cells to beta-oxidation products such as CD16:2c7t9 and CD16:2t8c10 and
      elongation products such as CD20:2c11t13, CD20:2t12c14 as well as CD22:2c13t15
      and CD22:2t14c16. Different CD16:2/CLA ratios observed between cells treated with
      different CLA isomers indicate that the metabolism of CLAs depends on the
      configuration of the conjugated double bonds. In conclusion, regarding the
      biological activity reported for CD20:2t12c14 and other metabolites of CLA, the
      present results indicate that metabolites of CLA are possibly also involved in
      mediating the anti-atherogenic actions of CLA.

PMID- 16567126
TI  - Presence and development of atrial fibrillation in chronic heart failure.
      Experiences from the MERIT-HF Study.
AB  - BACKGROUND: Atrial fibrillation is common in heart failure, but data regarding
      beta-blockade in these patients and its ability to prevent new occurrence of
      atrial fibrillation are scarce. METHODS: Baseline ECGs in MERIT-HF were coded
      regarding baseline rhythm, and outcome was analyzed in relation to rhythm.
      Occurrence of atrial fibrillation during follow-up was also analyzed. RESULTS: At
      baseline atrial fibrillation was diagnosed in 556 patients (13.9%). Mean
      metoprolol CR/XL dose in patients in atrial fibrillation (154 mg) and sinus
      rhythm (158 mg) was similar, as well as decrease in heart rate (14.8 and 13.7
      bpm, respectively). Only 61 (total of 362) deaths occurred in those in atrial
      fibrillation at baseline, 31 on placebo and 30 on metoprolol (RR 1.0; 95% CI 0.61
      1.65). During follow-up, new atrial fibrillation was observed in 85 patients on
      placebo and 47 patients on metoprolol (RR 0.53; 95% CI 0.37-0.76; p=0.0005).
      CONCLUSION: First, given the wide confidence interval, it was impossible to
      detect an interaction between metoprolol and mortality in patients with atrial
      fibrillation and heart failure. Second, in patients with sinus rhythm at
      baseline, metoprolol reduced the incidence of atrial fibrillation during follow
      up. However, we must be extremely cautious in over-interpreting effects in these
      subgroups.

PMID- 16567128
TI  - Risk assessment and prediction of Ixodes ricinus tick questing activity and human
      tick-borne encephalitis infection in space and time in the Czech Republic.
AB  - Present risk assessment and prediction of future risk of humans exposed to Ixodes
      (I.) ricinus tick attacks and, consequently, to tick-borne encephalitis (TBE)
      virus infection as one of the basic preconditions for successful TBE prevention
      has been intensively studied in the Czech Republic. An atlas of TBE in the Czech
      Republic containing predictive maps of I. ricinus high-incidence habitats and TBE
      risk sites identified by satellite data (Landsat 5 TM with spatial resolution 30
      m) at a scale of 1:200,000 over a territory of 52,000 km(2) and maps of human TBE
      case distribution (1971-2000) has been prepared using remote sensing and
      geographical information systems technologies. The influence of climate changes
      on a forest ecosystem inhabited by I. ricinus has been studied in the southern
      region of the Czech Republic. The analysis of long-term series (1931-2000) of
      climatologic and phenological characteristics has been carried out. The results
      are compared with the long-term series of TBE incidence. The influence of weather
      condition on day-to-day changes of I. ricinus host-seeking activities was studied
      in 2001-2004. Field observations were realized in the south-eastern periphery of
      Prague where the experimental plots for tick monitoring were established in a
      relevant type of forest growth (Querceto-carpinetum). I. ricinus activities were
      investigated by the flagging method on three plots (200 m(2) each) in weekly
      intervals (March to November) during 2001-2004. The instruments for
      micrometeorological observations were installed between the experimental plots.
      Macrometeorological data were used from the nearby Czech Hydrometeorological
      Institute first class meteorological observatory. Simple and multiple linear
      regression and quadratic regression were used to test the relation between
      weather modification and I. ricinus host-seeking activity. Two preliminary most
      suitable 'models' are demonstrated.

PMID- 16567127
TI  - Multidimensional scaling of pediatric sleep breathing problems and bio-behavioral
      correlates.
AB  - STUDY OBJECTIVES: Complex relationships exist between pediatric sleep disorders
      and daytime behavior. Using a multidimensional scaling model, we investigated
      these relationships in 126 children with sleep breathing disorders (SBD). METHOD:
      Validated questionnaires on nighttime behavior, daytime behavior, and respiratory
      health were administered to a large number of school children in Belgium.
      Children who met the criterion of having at least one sleep-related breathing
      problem (three or more times per week during the past six months) were selected
      for further analyses. A total of 26 indicators were defined and modeled,
      including sleep problems, sleep efficiency, sleep environment, sleep enuresis,
      internalised and externalised behavioral problems, respiratory health of the
      child and relatives, smoking exposure, and caffeine consumption. RESULTS: From
      3,045 questionnaire responses 4.1% of the children were reported to have a SBD
      symptom. SBD children differed on sleep and health domains from non-SBD children.
      Furthermore, through scaling of the (dis)similarities among the 26 indicators the
      SBD child was able to be modeled. By way of an internal analysis of the data
      matrix the following indicators were eliminated: sleep correlates, health of the
      family, and behavior rated by teachers, followed by caffeine intake, drugs, and
      behavior rated by the parents. This revealed a two-dimensional model, consisting
      of primary SBD and secondary SBD. CONCLUSION: Children with SBD differ on many
      domains from children without such disorders and an underlying two-fold SBD
      concept was found. Firstly, the SBD-indicator positioned in between investigated
      correlates with disorders of initiating and maintaining sleep and sleep
      hyperhydrosis on one hand and with respiratory-related illnesses on the other;
      this was labeled primary SBD. Secondly, the SDB-indicator not closely associated
      with any of the investigated correlates can be interpreted as secondary SBD.

PMID- 16567130
TI  - Altered feeding behaviour induced by long-term cisplatin in rats.
AB  - In animals without the emetic reflex, several emetogenic stimuli induce pica, an
      altered feeding behaviour consisting of the ingestion of non-nutritive
      substances. The development of pica in response to an emetogenic stimulus has
      been proposed to be useful as an indirect marker of nausea in the rat. In fact,
      like nausea and emesis in humans, it is accompanied by serotonin release from the
      enterochromaffin cells, increased c-fos labelling in the area postrema and the
      nucleus tractus solitarius, and a delay in gastric emptying. Furthermore, pica,
      measured as kaolin intake, is reduced by anti-emetic drugs. Pica has been
      demonstrated after single doses of cisplatin, the most emetogenic
      chemotherapeutic drug. However, cisplatin, as other antineoplastic drugs, is
      generally given in cycles, where conventional anti-emetics tend to lose
      efficiency. The aim of this work was to evaluate the pica induced by long-term
      treatment with cisplatin. Saline or cisplatin was administered once a week for 5
      consecutive weeks, and temperature, body weight, food ingestion and kaolin intake
      were measured on a daily basis. The influence of isolation (pica is necessarily
      studied in isolated animals) and exposure to kaolin (basal kaolin intake could
      modify pica itself and other parameters) on temperature, body weight and daily
      food ingestion was negligible in saline-treated rats. Cisplatin administered at 3
      mg/kg/week was too toxic: it produced hypothermia, weight drop and anorexia in
      both grouped and isolated rats, and 50% mortality in isolated animals. Toxicity
      associated with cisplatin administered at 1 mg/kg/week was acceptable, with a
      slower rate of weight gain being the major effect. In these rats, each cisplatin
      injection produced both acute anorexia and rebound hyperphagic responses. In
      addition, each administration induced both acute pica and an increase in basal
      kaolin intake, resembling the development of nausea in humans. This model could
      be useful for studying both the mechanisms leading to nausea associated with a
      long-term antineoplastic treatment and the efficiency of new anti-emetic drugs.

PMID- 16567129
TI  - Cardiac nociceptors innervated by vagal afferents in rats.
AB  - It is reported that cardiac afferent information is transmitted through at least
      three different pathways to the CNS: sympathetic, parasympathetic, and somatic;
      however, there are few studies concerning the role of afferent fibers of vagus
      nerves for eliciting cardiac sensation including pain. Especially, receptive
      field properties innervated by single vagal nerve fiber and mechanical threshold
      of nociceptors on the cardiac surface are not yet quantitatively studied.
      Therefore, in this study, we systematically investigated characteristics of vagal
      units innervating cardiac nociceptors in rats. Using anesthetized and
      artificially ventilated rats, 37 single unit recordings were made from fine nerve
      filaments of the left vagal nerve. For quantitative mechanical stimulation, the
      cardiac surface was stimulated by a von Frey type device. In addition, bradykinin
      was used for checking the chemical sensitivity of the nociceptor. Electrical
      stimulation was used to estimate the conduction velocity of the recorded nerve
      fiber. All units recorded from the vagal nerve were either Adelta- or C-polymodal
      nociceptors. About 70% of the afferents had conduction velocities in the C-fiber
      range. In 60% of the units, the peripheral receptive field covered spot-like
      areas, but we also found larger and continuous receptive fields. Our results show
      that a majority of nociceptors innervated by vagal afferents are the C-polymodal
      type with spot-like receptive fields. We consider it to relate to the ambiguous
      and dull pain of angina pectoris.

PMID- 16567131
TI  - The role of tachykinins in circular muscle contractility of the murine ileum: a
      functional investigation.
AB  - We investigated the participation of different tachykinin receptors in
      contractility of circular muscle strips of the mouse ileum using selective NK
      receptor agonists and antagonists. The NK1 receptor agonist septide (1-100 nM)
      induced dose-dependent contractions which were reduced by atropine and augmented
      by L-NNA. L-NNA increased and TTX consecutively reduced contractions to the NK2
      receptor agonist beta-A-NKA (1-100 nM). Senktide, agonist of NK3 receptors,
      failed to induce contractions. NANC contractions to EFS were decreased after NK1
      receptor blockade with RP67580. This inhibitory effect was more pronounced after
      additional blockade of NK2 and NK3 receptors. NK3 receptor antagonism alone
      reduced contractions at higher frequencies of stimulation. When the duration of
      the EFS stimulus was increased, the participation of all NK receptor subtypes
      became more evident. Our results suggest that excitatory NANC transmission in the
      circular muscle layer of the mouse ileum is mediated by tachykinins acting
      principally on NK1 receptors on cholinergic nerves and smooth muscle cells. Also
      NK2 receptors, located on smooth muscle cells and nitrergic neurons, and NK3
      receptors on enteric neurons are involved.

PMID- 16567132
TI  - Differentiated hemodynamic changes controlled by splanchnic nerve.
AB  - The splanchnic (SPL) nerve is a postganglionic sympathetic nerve involved in the
      tonic regulation of the cardiovascular system. Electrical stimulation of this
      nerve produces mesenteric vasoconstriction and it has been assumed that
      vasodilatory responses are dependent on inhibition of the vasoconstrictor tone.
      Several different central stimuli have been shown to dilate the hindquarter
      vascular bed and constrict the mesenteric vascular bed. To determine whether
      vasodilatory and vasoconstrictor effects in different vascular beds are elicited
      by activation of different sympathetic nerves, we investigated the hemodynamic
      changes in hindquarter, mesenteric and renal vascular beds evoked by electrical
      stimulation of the SPL nerve. Stimulation of the intact or sectioned SPL nerve in
      chloralose-anesthetized, artificially ventilated rats evoked increases in the
      hindquarter vascular conductance and simultaneously decreased the mesenteric and
      renal vascular conductance. Intravenous (i.v.) administration of L-NAME prior to
      stimulation of the proximal end of the sectioned SPL nerve abolished the increase
      in hindquarter conductance, suggesting the involvement of nitric oxide in this
      response. In assessing the hemodynamic effects of tonic activity on the SPL
      nerves, no significant changes were observed after unilateral section of the SPL
      nerve, but bilateral section of the SPL nerves decreased hindquarter conductance
      and did not significantly change the mesenteric conductance simultaneously. No
      consistent response was observed in the renal vascular bed after unilateral and
      subsequent contralateral section of the SPL nerves. These findings demonstrate
      that electrical stimulation of the SPL nerve produces mesenteric vasoconstriction
      and simultaneous hindquarter vasodilatation, which is mediated by nitric oxide.
      Moreover, the present data suggest that SPL nerves may provide a tonic
      vasodilatory tone in the hindquarter vascular bed and simultaneously a
      vasoconstrictor tone in another, undetermined vascular bed.

PMID- 16567133
TI  - DNA-PK phosphorylates histone H2AX during apoptotic DNA fragmentation in
      mammalian cells.
AB  - The phosphorylation of histone H2AX at serine 139 is one of the earliest
      responses of mammalian cells to ionizing radiation-induced DNA breaks. DNA breaks
      are also generated during the terminal stages of apoptosis when chromosomal DNA
      is cleaved into oligonucleosomal pieces. Apoptotic DNA fragmentation and the
      consequent chromatin condensation are important for efficient clearing of genomic
      DNA and nucleosomes and for protecting the organism from auto-immmunization and
      oncogenic transformation. In this study, we demonstrate that H2AX is
      phosphorylated during apoptotic DNA fragmentation in mouse, Chinese hamster
      ovary, and human cells. We have previously shown that ataxia telangiectasia
      mutated kinase (ATM) is primarily responsible for H2AX phosphorylation in murine
      cells in response to ionizing radiation. Interestingly, we find here that DNA
      dependent protein kinase (DNA-PK) is solely responsible for H2AX phosphorylation
      during apoptosis while ATM is dispensable for the process. Moreover, the kinase
      activity of DNA-PKcs (catalytic subunit of DNA-PK) is specifically required for
      the induction of gammaH2AX. We further show that DNA-PKcs is robustly activated
      in apoptotic cells, as evidenced by autophosphorylation at serine 2056, before it
      is inactivated by cleavage. In contrast, ATM is degraded well before DNA
      fragmentation and gammaH2AX induction resulting in the predominance of DNA-PK
      during the later stages of apoptosis. Finally, we show that DNA-PKcs
      autophosphorylation and gammaH2AX induction occur only in apoptotic nuclei with
      characteristic chromatin condensation but not in non-apoptotic nuclei from the
      same culture establishing the most direct link between DNA fragmentation, DNA
      PKcs activation, and H2AX phosphorylation. It is well established that DNA-PK is
      inactivated by cleavage late in apoptosis in order to forestall DNA repair. Our
      results demonstrate, for the first time, that DNA-PK is actually activated in
      late apoptotic cells and is able to initiate an early step in the DNA-damage
      response, namely H2AX phosphorylation, before it is inactivated by proteolysis.

PMID- 16567134
TI  - Measurement of drug-protein binding by immobilized human serum albumin-HPLC and
      comparison with ultrafiltration.
AB  - An HPLC method employing CHIRAL-I (150 mm x 3 mm), 5 microm column from Chrom.
      Tech., immobilized with human serum albumin (HSA), was used to determine in vitro
      protein binding of several compounds. Experimentally obtained plasma protein data
      exhibited good correlation with the reported values. The method was compared with
      the conventional ultra filtration technique and both yielded similar results.
      Proprietary compounds that could not be analyzed by ultra filtration due to high
      non-specific binding to filter membrane were successfully analyzed by HSA-HPLC
      method. On the other hand, two proprietary compounds did not elute from HSA
      column due to strong binding, but were successfully analyzed by ultra filtration.
      This proves that both the techniques have their own merits and demerits and
      should be exploited judiciously as per the requirement. The plasma protein
      binding studies conducted on four gyrase inhibitors in rat and human plasma
      exhibited no interspecies difference via ultra filtration method. Further, it was
      also observed that the protein binding obtained for the four gyrase inhibitors by
      HSA-HPLC method was not only similar to that obtained by ultra filtration in
      human plasma but was also in accordance with ex vivo and in vitro protein binding
      obtained for rat plasma after ultra filtration because these compounds
      predominantly bind to HSA The binding of several compounds to alpha1-acid
      glycoprotein (AGP), another important plasma protein, was also examined using AGP
      immobilized column. However, the data could not be relied upon since some anti
      bacterials and non-steroidal anti-inflammatory drugs (NSAIDS), which are known to
      predominantly bind to HSA, were also found to bind to AGP.

PMID- 16567135
TI  - Determination of limiting mobilities and dissociation constants of 21 amino acids
      by capillary zone electrophoresis at very low pH.
AB  - The dependence of the effective electrophoretic mobility on pH of the background
      electrolyte was experimentally determined by capillary zone electrophoresis (CZE)
      for cationic forms of amino acids. The pH of the background electrolytes was in
      the highly acidic range, 1.6-2.6 pH units, to ensure a high degree of protonation
      of the amino acids. Poly(vinyl alcohol) was added to the background electrolytes
      to avoid possible adsorption of the analytes at the inner capillary wall. Non
      linear regression of the experimental data was applied to obtain the parameters
      of the relevant regression functions--the actual mobilities and mixed
      dissociation constants corresponding to the actual ionic strength. The extended
      Onsager and Debye-Huckel law was used to calculate the limiting mobilities and
      thermodynamic dissociation constants. The comparison of the experimental
      electropherogram with the computer prediction by PeakMaster using the determined
      data is presented for the selected sample of amino acids.

PMID- 16567136
TI  - Validated LC-MS-MS method for determination of m-nisoldipine polymorphs in rat
      plasma and its application to pharmacokinetic studies.
AB  - A sensitive and specific liquid chromatography-tandem mass spectrometric (LC-MS
      MS) method has been developed to determine m-nisoldipine in rat plasma. Sample
      was pretreated by a single-step protein precipitation with acetonitrile, in
      contrast to the liquid-liquid procedure frequently used for the extraction of 1,4
      dihydropyridines from biologic samples. Separation of analyte and internal
      standard (I.S.) was performed on a Symmetry RP-C(18) analytic column (50 mm x 4.6
      mm, 3.5 microm) with a mobile phase consisting of acetonitrile-water (80:20, v/v)
      at a flow rate of 0.5 ml/min. The API 4000 triple quadrupole mass spectrometer
      was operated in multiple reaction monitoring (MRM) scan mode using TurboIonSpray
      ionization (ESI) source. The method was sensitive with a lower limit of
      quantification (LLOQ) of 0.2 ng/mL, with good linearity (r>or=0.9982) over the
      linear range of 0.2-20 ng/mL. All the validation data, such as accuracy,
      precision, and inter-day repeatability, were within the required limits. The
      method was successfully applied to pharmacokinetic and relative bioavailability
      studies of m-nisoldipine polymorphs in rats.

PMID- 16567137
TI  - Determination of the enantiomeric composition of a new insulin sensitizer in
      plasma samples from non-clinical and clinical investigations using chiral HPLC
      with electrospray tandem mass spectrometric detection.
AB  - Two drug assays were developed and applied to assess the enantiomeric composition
      of an insulin sensitizer drug in plasma after administration of its racemate to
      man, and in human and animal plasma and serum samples generated after in vitro
      experiments. The sample preparation for the assays consisted either of protein
      precipitation and column-switching, or liquid-liquid extraction and direct
      injection. Subsequently, both assays employed chiral HPLC coupled to atmospheric
      pressure ionization mass spectrometry. An interconversion of the racemate to a
      mixture enriched with the (+)-enantiomer could be confirmed for all species and
      biological matrices. The individual enantiomers could be quantified in the
      concentration range 0.5-500 ng/ml, starting with a 100-microl plasma aliquot.
      Inter- and intra-assay precision and accuracy were in the range 0.1-7.9 and 88.8
      106.0%, respectively. Run times of 5 min for a single sample allows the analysis
      of more than 200 samples overnight.

PMID- 16567139
TI  - Eating behaviors to grow on.

PMID- 16567138
TI  - Long wave ultrasound may enhance bone regeneration by altering OPG/RANKL ratio in
      human osteoblast-like cells.
AB  - Human osteoblast cell line (MG63) cells were treated with long wave (45 kHz,
      intensity 30 mW/cm(2)) continuous ultrasound (US) for 5 min and incubated for
      various time periods following the treatment. The reverse transcriptase
      polymerase chain reaction (RT-PCR) technique was used for observing the genetic
      expression and real-time PCR for quantitative analysis of receptor activator of
      NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) along with alkaline
      phosphatase (ALP), an early bone marker, and osteocalcin (OCN) a late marker.
      ELISA was performed to estimate the amount of the cytokine released into the
      culture media. The osteoblasts responded to US by significantly upregulating both
      the OPG mRNA and protein levels. There was no RANKL mRNA expression observed in
      both the US and control groups and the protein levels were also very low in both
      groups. There was also no TNF-alpha expression and the TNF-alpha protein levels
      were insignificant. ALP and OCN mRNA were significantly upregulated in the US
      group. To our knowledge, this is the first study that shows the effect of US on
      OPG, RANKL and TNF-alpha expression. US appears to upregulate OPG and may
      downregulate RANKL production. From these findings, we conclude that therapeutic
      ultrasound may increase bone regeneration by altering the OPG/RANKL ratio in the
      bone microenvironment.

PMID- 16567140
TI  - ADA's growing membership: let's celebrate... and then repeat... and repeat...

PMID- 16567142
TI  - Infant feeding: can we spice it up a bit?

PMID- 16567143
TI  - Communication is the heart of provider-patient relationship.

PMID- 16567144
TI  - Centers for Medicare & Medicaid Services telehealth coverage of MNT--what ADA
      members need to know.

PMID- 16567145
TI  - Promoting health in an unhealthful environment: lifestyle challenges for children
      and adolescents.

PMID- 16567146
TI  - Does dieting increase the risk for obesity and eating disorders?

PMID- 16567147
TI  - Adolescent and parent views of family meals.
AB  - OBJECTIVE: To examine and compare the family mealtime environment from the
      perspectives of both adolescents and parents. DESIGN: Adolescents completed a
      school-based survey and parents participated in a telephone interview as part of
      Project EAT (Eating Among Teens). SUBJECTS/SETTING: Participants were 902
      adolescent females (n=424) and males (n=478) and one of their guardians/parents.
      STATISTICAL ANALYSES PERFORMED: Frequencies, chi(2) analyses, and Spearman
      correlations were used to assess relationships. RESULTS: Parents were more likely
      than adolescents to report eating five or more family meals per week, the
      importance of eating together, and scheduling difficulties (P<0.001). Younger
      adolescents were more likely than older adolescents to report eating five or more
      family meals per week, higher importance of eating together, and more rule
      expectations at mealtime (P<0.001), whereas older adolescents were more likely to
      report scheduling difficulties (P<0.001). Girls reported more family meals per
      week and more scheduling conflicts than boys did; boys reported more rules at
      mealtime than girls did (P<0.001). CONCLUSIONS: Family meals are perceived
      positively by both adolescents and parents. Family meals may be a useful
      mechanism for enhancing family togetherness, and for role modeling behaviors that
      parents would like their children to emulate. Dietetics professionals can
      capitalize on positive attitudes toward family meals to help promote their
      frequency. Helping families learn to cook healthful, quick meals may reduce
      dependency on less healthful meal options, reduce the frequency of eating outside
      of the home, and promote greater nutritional intake.

PMID- 16567148
TI  - Family mealtimes: more than just eating together.

PMID- 16567149
TI  - Dairy and dairy-related nutrient intake during middle childhood.
AB  - OBJECTIVE: To characterize patterns of dairy intake among girls in middle
      childhood. DESIGN: Longitudinal data were used to characterize girls' patterns of
      dairy intake at age 5, 7, 9, and 11 years. SUBJECTS: Participants were 151 girls
      from predominately middle-class and exclusively non-Hispanic white families
      living in central Pennsylvania. STATISTICAL ANALYSES: Intakes of dairy, energy,
      macronutrients, vitamin D, calcium, and phosphorus were assessed using three 24
      hour dietary recalls in 151 non-Hispanic white girls at age 5, 7, 9, and 11
      years. Analyses of changes over time were conducted using repeated measures
      analysis of variance. McNemar's chi(2) test was used to analyze change in
      percentage of dairy consumers over time. RESULTS: From age 5 to 11 years, girls'
      total dairy intake remained stable. Total milk consumption declined, due to a
      decline in intake of milk as a beverage, while intakes of cheese and dairy
      desserts increased. Much of the decline in milk intake from age 5 to 11 years,
      especially for milk as a beverage, was due to a reduction in the percentage of
      girls consuming milk as a beverage, not simply due to a decline in the servings
      of milk as a beverage consumed by consumers. On average, girls met vitamin D
      recommendations over time; however, by age 9 and 11 years girls failed to meet
      calcium and phosphorus recommendations. CONCLUSIONS: Although girls' dairy intake
      was stable over time, at age 7, 9, and 11 years girls did not meet the
      recommended three servings per day, leading to suboptimal intakes of calcium and
      phosphorus at age 9 and 11 years. Increasing milk intake among all children
      should continue to be a major focus of interventions.

PMID- 16567150
TI  - Larger portion sizes lead to a sustained increase in energy intake over 2 days.
AB  - OBJECTIVE: We tested the effect on energy intake of increasing the portion size
      of all foods and beverages served over 2 consecutive days. DESIGN: The study used
      a randomized crossover design. SUBJECTS/SETTING: Subjects were 32 adults from a
      university community. INTERVENTION: For 2 consecutive days in each of 3 weeks,
      subjects ate their main meals in a controlled setting and were given snacks for
      consumption between meals. We used the same two daily menus each week, but varied
      the portion sizes of all foods and beverages served in a given week (either 100%,
      150%, or 200% of baseline amounts). MAIN OUTCOME MEASURES: Energy intake and
      ratings of hunger and satiety were measured. STATISTICAL ANALYSES PERFORMED: A
      linear mixed model with repeated measures was used. RESULTS: There was a
      significant effect of portion size on energy intake in both men and women
      (P<0.0001). Increasing portions by 50% increased daily energy intake by 16%
      (women: 335 kcal/day; men: 504 kcal/day), and increasing portions by 100%
      increased intake by 26% (women: 530 kcal/day; men: 812 kcal/day). Energy intake
      did not differ between the 2 days of each week. Daily ratings of fullness were
      lowest in the 100% portion condition (P=0.0004), but did not differ significantly
      in the 150% and 200% conditions. CONCLUSIONS: Increasing the portion size of all
      foods resulted in a significant increase in energy intake that was sustained over
      2 days. These data support suggestions that large portions are associated with
      excess energy intake that could contribute to increased body weight.

PMID- 16567151
TI  - Higher satiety ratings following yogurt consumption relative to fruit drink or
      dairy fruit drink.
AB  - OBJECTIVES: To compare the satiating power of semisolid and liquid yogurts with
      fruit beverages and dairy fruit drinks. DESIGN AND PROCEDURES: Thirty-two
      volunteers (16 men and 16 women), ages 18 to 35 years, consumed a 200-kcal
      preload stimulus on four separate occasions. A tray lunch was presented 90
      minutes after the preload and food consumption was measured. METHODS: The stimuli
      were: a semisolid yogurt containing pieces of peach and eaten with a spoon (378
      g), the same yogurt in a drinkable homogenized form (378 g), a peach-flavored
      dairy beverage (400 mL), and a peach juice beverage (400 mL). Participants rated
      hunger, thirst, satiety, and desire to eat at baseline and at 20-minute intervals
      after ingestion. RESULTS: The two yogurts (semisolid and liquid) led to lower
      hunger and higher fullness ratings as compared with the fruit drink or dairy
      fruit drink. There was no difference in satiety profiles between the yogurt that
      was eaten with a spoon and the drinkable version. Energy intakes at lunch were
      the same across all four conditions (mean+/-standard deviation, 806+/-43 kcal).
      CONCLUSIONS: The two yogurts were more satiating than the two beverages. However,
      lower hunger and higher fullness ratings after yogurt consumption did not lead to
      energy compensation at the next meal.

PMID- 16567152
TI  - Obesity, disordered eating, and eating disorders in a longitudinal study of
      adolescents: how do dieters fare 5 years later?
AB  - OBJECTIVE: To determine if adolescents who report dieting and different weight
      control behaviors are at increased or decreased risk for gains in body mass
      index, overweight status, binge eating, extreme weight-control behaviors, and
      eating disorders 5 years later. DESIGN: Population-based 5-year longitudinal
      study. PARTICIPANTS: Adolescents (N=2,516) from diverse ethnic and socioeconomic
      backgrounds who completed Project EAT (Eating Among Teens) surveys in 1999 (Time
      1) and 2004 (Time 2). MAIN OUTCOME MEASURES: Weight status, binge eating, extreme
      weight control, and self-reported eating disorder. STATISTICAL ANALYSIS: Multiple
      linear and logistic regressions. RESULTS: Adolescents using unhealthful weight
      control behaviors at Time 1 increased their body mass index by about 1 unit more
      than adolescents not using any weight-control behaviors and were at approximately
      three times greater risk for being overweight at Time 2 (odds ratio [OR]=2.7 for
      girls; OR=3.2 for boys). Adolescents using unhealthful weight-control behaviors
      were also at increased risk for binge eating with loss of control (OR=6.4 for
      girls; OR=5.9 for boys) and for extreme weight-control behaviors such as self
      induced vomiting and use of diet pills, laxatives, and diuretics (OR=2.5 for
      girls; OR=4.8 for boys) 5 years later, compared with adolescents not using any
      weight-control behaviors. CONCLUSIONS: Dieting and unhealthful weight-control
      behaviors predict outcomes related to obesity and eating disorders 5 years later.
      A shift away from dieting and drastic weight-control measures toward the long
      term implementation of healthful eating and physical activity behaviors is needed
      to prevent obesity and eating disorders in adolescents.

PMID- 16567153
TI  - Nutrigenomics: from molecular nutrition to prevention of disease.
AB  - Until recently, nutrition research concentrated on nutrient deficiencies and
      impairment of health. The advent of genomics-interpreted broadly as a suite of
      high throughput technologies for the generation, processing, and application of
      scientific information about the composition and functions of genomes-has created
      unprecedented opportunities for increasing our understanding of how nutrients
      modulate gene and protein expression and ultimately influence cellular and
      organismal metabolism. Nutritional genomics (nutrigenomics), the junction between
      health, diet, and genomics, can be seen as the combination of molecular nutrition
      and genomics. The diverse tissue and organ-specific effects of bioactive dietary
      components include gene-expression patterns (transcriptome); organization of the
      chromatin (epigenome); protein-expression patterns, including posttranslational
      modifications (proteome); as well as metabolite profiles (metabolome).
      Nutrigenomics will promote an increased understanding of how nutrition influences
      metabolic pathways and homeostatic control, how this regulation is disturbed in
      the early phases of diet-related disease, and the extent to which individual
      sensitizing genotypes contribute to such diseases. Eventually, nutrigenomics will
      lead to evidence-based dietary intervention strategies for restoring health and
      fitness and for preventing diet-related disease. In this review, we provide a
      brief overview of nutrigenomics from our point of view by describing current
      strategies, future opportunities, and challenges.

PMID- 16567154
TI  - Key facilitators and best practices of hotel-style room service in hospitals.
AB  - This qualitative study sought to identify the features, advantages, and
      disadvantages of hotel-style room service; the barriers to, and facilitators for,
      implementing the process; and "best practices." The study took place in four
      heterogeneous hospitals. Participants included hospital administrators, managers,
      and room-service employees. Data-collection methods included semi-structured
      interviews, observations, and document analysis. Common features of hotel-style
      room service were meal delivery within 30 to 45 minutes, a restaurant-style menu,
      procedures to feed ineligible patients, tray assembly on demand, scripting, and
      waitstaff uniforms for room-service employees. The major barrier to implementing
      room service was obtaining nursing support. The key facilitators were the
      hospital's service-oriented culture, using a multidisciplinary planning team,
      engaging nursing departments early in the planning stages, and intense customer
      service training of room-service employees. The overwhelming advantage was
      patients' control over their food choices. The main disadvantage was cost.
      Initial best practices in hotel-style room service include: (a) taking a
      multidisciplinary team approach for developing and implementing the process, (b)
      customer-service training, (c) using a customer-driven menu, (d) wearing
      waitstaff uniforms, and (e) using carts with airpots for dispensing hot
      beverages.

PMID- 16567155
TI  - Effects of dietary protein intake on indexes of hydration.
AB  - This study aims to characterize the relationship between increased protein intake
      and hydration indexes. Five men participated in a 12-week, randomized, crossover,
      controlled diet intervention study. Subjects consumed eucaloric diets containing
      3.6 (high protein), 1.8 (moderate protein), and 0.8 (low protein) g/kg/day of
      protein for 4 weeks each. Energy intakes were based on requirements established
      relative to resting energy expenditure and activity at baseline. Assessments
      included blood urea nitrogen, plasma osmolality, urine-specific gravity, and
      estimates of fluid balance. Repeated-measures analyses of variance and paired t
      tests were used to determine effects of treatment and time. Fluid intake and
      fluid balance were unaffected. Blood urea nitrogen was higher for high protein vs
      low protein and vs moderate protein, and urine-specific gravity was higher for
      high protein vs moderate protein. Baseline plasma osmolality was greater for high
      protein vs low protein and vs moderate protein. The effect of increasing dietary
      protein on fluid status was minimal.

PMID- 16567156
TI  - Acceptability of soymilk as a calcium-rich beverage in elementary school
      children.
AB  - Dairy products are the main source of calcium in the National School Lunch
      Program. Children who avoid dairy products because of lactose intolerance or
      other concerns can benefit from the availability of another calcium-rich beverage
      in the National School Lunch Program. This study assessed whether elementary
      school children would select and consume calcium-fortified soymilk in school
      cafeterias and whether the addition of soymilk would increase the percentage of
      students selecting a calcium-rich beverage at lunch. The ratio of saturated fat
      to calcium consumed from calcium-rich beverages with and without the availability
      of soymilk was also determined. After 4 weeks of soymilk availability, 22.3% of
      students chose soymilk and consumed an average of 58% of each carton, whereas
      77.6% chose dairy milk and consumed an average of 52.6%. Total calcium-rich
      beverage selection with lunch increased from 79% to 83.1%. Calcium consumption
      per gram of saturated fat consumed from calcium-rich beverages also rose from 194
      mg to 237 mg with the addition of soymilk.

PMID- 16567157
TI  - Sensory evaluation ratings and melting characteristics show that okra gum is an
      acceptable milk-fat ingredient substitute in chocolate frozen dairy dessert.
AB  - Reducing dietary fat intake may lower the risk of developing coronary heart
      disease. This study examined the feasibility of substituting okra gum for 25%,
      50%, 75%, or 100% milk fat in frozen chocolate dairy dessert. Fifty-six consumers
      evaluated the frozen dairy desserts using a hedonic scale. Consumers rated color,
      smell, texture, flavor, aftertaste, and overall acceptability characteristics of
      all products as acceptable. All ratings were similar among the products except
      for the aftertaste rating, which was significantly lower for chocolate frozen
      dairy dessert containing 100% milk-fat replacement with okra gum compared with
      the control (0% milk-fat replacement) (P<0.05). Whereas melting points of all
      products were similar, melting rates slowed significantly as milk-fat replacement
      with okra gum increased, suggesting that okra gum may increase the stability of
      frozen dairy desserts (P<0.05). Overall, this study shows that okra gum is an
      acceptable milk-fat ingredient substitute in chocolate frozen dairy dessert.

PMID- 16567158
TI  - Does eating during television viewing affect preschool children's intake?
AB  - The objective of this study was to examine the effects of television (TV) viewing
      on children's lunch and snack intake in one condition when the children watched a
      22-minute cartoon video on TV (TV group), and in another without the TV (no TV
      group). Participants included 24 children and their parents, recruited from a
      university child-care center. Parents reported children's TV viewing habits at
      home. Overall, children ate significantly less snack and lunch in the TV
      condition compared with the no TV condition. However, children who reportedly
      watched more daily hours of TV and who had a higher frequency of meals eaten in
      front of the TV at home ate more lunch in the TV condition. TV viewing may either
      increase or reduce children's intake, depending on prior experience with eating
      during TV viewing.

PMID- 16567159
TI  - Where can I find information on the oxalate content of foods?

PMID- 16567161
TI  - Segmental multicystic dysplasia and ureteropelvic junction obstruction in a
      nonduplicated kidney.
AB  - A 2-month-old child presented for evaluation of prenatal hydronephrosis. Imaging
      studies were consistent with a right duplex system with a dysplastic,
      nonfunctioning upper pole and lower pole ureteropelvic junction obstruction. We
      proceeded with removal of the upper pole and pyeloplasty and were surprised to
      find a single collecting system with a cystic, dysplastic upper pole segment and
      the absence of an upper pole pelvis or ureter. The rare diagnosis of a segmental
      multicystic dysplastic kidney with ipsilateral ureteropelvic junction obstruction
      was made. We present a review of the case and of previous literature on this
      topic.

PMID- 16567160
TI  - Alpha-synuclein facilitates the toxicity of oxidized catechol metabolites:
      implications for selective neurodegeneration in Parkinson's disease.
AB  - Free radicals, including dopamine (DA)-oxidized metabolites, have long been
      implicated in pathogenesis of Parkinson's disease (PD). However, the
      relationships between such oxidative stresses and alpha-synuclein (alpha-S), a
      major constituent of Lewy bodies, remain unknown. In this study, we established
      neuronal cells that constitutively express alpha-S and tetracycline-regulated
      tyrosinase. While tyrosinase overexpression induced apoptosis, co-expression of
      wild type or A53T mutant human alpha-S with tyrosinase further exacerbated cell
      death. In this process, the formation of alpha-S oligomers and the reduction in
      mitochondrial membrane potential were demonstrated. This cellular model may
      reconstitute the pathological metabolism of alpha-S in the synucleinopathy and
      provide a useful tool to explore possible pathomechanisms of nigral degeneration
      in PD.

PMID- 16567163
TI  - Preperitoneal pelvic packing in the child with an unstable pelvis: a novel
      approach.
AB  - Combined external pelvic fixation and preperitoneal pelvic packing may represent
      a revolutionary management strategy for mechanically unstable pelvis fractures in
      critically injured patients.

PMID- 16567162
TI  - A case report of glial choristoma of the tongue.
AB  - Glial choristoma of the tongue is extremely rare. The authors report the case of
      a 9-day-old infant with a congenital lingual glial choristoma. Complete surgical
      excision was performed without postoperative complications or recurrence. The
      authors also present a review of the literature and outcome of this benign tumor.

PMID- 16567164
TI  - Nonresectable inflammatory pseudotumor of the porta hepatis.
AB  - Inflammatory pseudotumors are rare mass lesions often mistaken for malignancy.
      Currently, only 2 cases of pseudotumors originating from the porta hepatis have
      been reported in the pediatric literature, and both cases were those of patients
      older than 30 years. When located in the porta hepatis, pseudotumors are
      difficult to treat via surgical resection, and other therapeutic options must be
      considered. We report a pediatric case of inflammatory pseudotumor of the porta
      hepatis and discuss the different surgical and nonsurgical options used in
      treating pseudotumors.

PMID- 16567165
TI  - Congenital nasal pyriform aperture stenosis: a rare cause of neonatal nasal
      obstruction.
AB  - Congenital nasal pyriform aperture stenosis has been described as an unusual
      cause of neonatal nasal obstruction. Clinical suspicion is based on respiratory
      distress, cyclic cyanosis, apneas, and feeding difficulties. A bony overgrowth of
      the maxillary nasal processes is thought to be responsible for this deformity.
      This anomaly has been reported as an isolated feature or can be associated with
      craniofacial or central nervous system anomalies. Surgery is indicated in cases
      of severe respiratory distress, feeding difficulties, and when conservative
      methods fail.

PMID- 16567166
TI  - Prevention of heart failure in the management of congenital diaphragmatic hernia
      by maintaining ductal patency. A case report.
AB  - Congenital diaphragmatic hernia is a rare entity in childhood carrying a high
      mortality rate of 30% to 50%. Ipsilateral pulmonary hypoplasia, increased
      pulmonary vascular resistance, and potential cardiac failure complicate early
      postnatal life. Surgical correction can either be performed on the first day of
      life or be deferred to a time after stabilization of the infant. Our patient
      presented with a left-sided Bochdalek's hernia containing large and small bowel.
      She required intubation and resuscitation on day 1 of life, and surgical repair
      had to be postponed. Further respiratory deterioration required commencement of
      inhaled nitric oxide and high-frequency ventilation. Pulmonary artery pressure
      rose to suprasystemic level. Closure of the ductus arteriosus on day 8 resulted
      in imminent right-sided heart failure. Commencement of alprostadil (prostaglandin
      E1) reopened the ductus and stabilized the patient. Surgical repair was
      successful 3 days later. Alprostadil should be considered as an important
      component of therapy in severe cases of congenital diaphragmatic hernia, where
      deterioration of right-sided heart function occurs.

PMID- 16567167
TI  - Absence of the p53 tumor suppressor gene promotes osteogenesis in mesenchymal
      stem cells.
AB  - OBJECTIVE: Osteosarcoma arises predominantly in the metaphyseal growth plate of
      children during the growth spurt years. These tumors develop during physiological
      growth from an expanding cell population, suggesting that the transformed cell is
      a bone-forming progenitor. An absence of the p53 oncogene has been implicated in
      the origin and progression of osteosarcoma, and because mesenchymal stem cells
      (MSCs) are the physiological osteogenic progenitor cell population, we
      hypothesized that a p53-/- mutation would enhance bone differentiation of MSC in
      a mouse model of in vitro osteogenesis. METHODS: Clonal MSC populations were
      derived from p53-/- mice. P53-/- and wild-type cells were placed in osteogenic
      culture and assessed via Alizarin Red quantification and alkaline phosphatase
      staining. The osteogenic marker genes Cbfa1, osteopontin, and osteocalcin were
      assessed by quantitative real time polymerase chain reaction during
      differentiation. RESULTS: Bone nodule formation and alkaline phosphatase staining
      was accelerated and enhanced in the p53-/- cells. The early and intermediate
      osteogenic markers, Cbfa1 and osteopontin, were upregulated in p53-/- MSCs
      compared with wild-type cells during osteogenesis. The terminal osteogenic marker
      gene osteocalcin was paradoxically lower in p53-/- MSCs indicating impaired
      terminal differentiation. CONCLUSION: The p53-/- mutation enhances and
      accelerates early osteogenesis in MSCs, but prevents terminal differentiation
      toward a mature osteocyte phenotype. These findings may have important
      implications for the regulation of the MSC compartment during the derivation of
      osteosarcoma in children.

PMID- 16567168
TI  - Outcome after surgical resection of recurrent rhabdomyosarcoma.
AB  - BACKGROUND/PURPOSE: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma
      in children. Patients with localized disease have a cure rate of 50% to 90%;
      however, there has been little evidence that aggressive surgical resection for
      recurrent disease is of benefit. We reviewed our experience with aggressive
      surgical resection for recurrent RMS. METHODS: A retrospective review of the
      records for patients with RMS was performed. Data extracted included tumor site,
      histology, initial therapy, time to recurrence, treatment, and outcomes. RESULTS:
      From 1991 to 2002, 122 patients with RMS (3 months-18 years) were treated at the
      MD Anderson Cancer Center. Of 32 patients with recurrent RMS, 19 had surgical
      resection and 13 had biopsy only or no resection. The common primary sites
      included extremity (12), genitourinary nonbladder/prostate (7), and
      retroperitoneal/trunk (7). In the resection group, 33 operations were performed
      with 5 (15%) major complications and no deaths. Seventeen (52%) of these
      procedures (7 pelvic, 5 thoracic, 3 amputations, and 2 cranial) were classified
      as aggressive. After a mean follow-up period of 4.9 years, 7 patients (37%) had
      no evidence of disease, 8 (42%) died, and 4 were lost to follow-up. There was no
      correlation between survival and the type of resection. In the no-resection group
      only, 1 (8%) of 13 patients survived. CONCLUSIONS: Despite morbidity, aggressive
      surgical resection is warranted to improve survival in patients with recurrent
      RMS.

PMID- 16567169
TI  - Neuroblastoma detection using serum proteomic profiling: a novel mining technique
      for cancer?
AB  - BACKGROUND: Serum proteins in neuroblastoma (NB), such as neuron-specific enolase
      and lactate dehydrogenase, are used as nonspecific markers of disease severity.
      In this study, we have generated serum protein profiles that correlate with NB by
      applying proteomic technologies to uncover, at the protein level, serum
      polypeptide expression patterns in patients with NB. METHODS: Surface-enhanced
      laser desorption/ionization-time-of-flight mass spectrometry was used to generate
      protein expression spectra in human NB (group I, n = 18) and healthy children
      (group II, n = 17) sera. Groups I and II mass spectral data were compared after
      baseline subtraction. Peaks with high signal-to-noise ratios were selected and
      grouped into bins with various intervals along mass-to-charge axis. Two-sample t
      test and 3-fold cross validation were used to identify differential biomarkers
      between groups I and II. RESULTS: Significant differentially expressed proteins
      were identified between groups I and II (P < or = .05). The discriminatory
      features (proteomic patterns) of cancer from normal sera were successfully
      identified using the classification algorithm. The average classification
      performance after 3-fold cross validation was 87.26%. CONCLUSION: Surface
      enhanced laser desorption/ionization-time-of-flight mass spectrometry is suitable
      for preliminary assessment of NB and could potentially provide a noninvasive
      diagnosis of NB. We propose that surface-enhanced laser desorption/ionization
      provides a novel method for NB diagnosis because direct observations of spectral
      differences between normal and NB sera are possible.

PMID- 16567170
TI  - Bilateral staged versus bilateral simultaneous thoracotomy in the pediatric
      population.
AB  - AIM: The aim of the study was to evaluate the safety and outcomes of simultaneous
      bilateral thoracotomy in pediatric patients compared with traditional bilateral
      staged thoracotomy. METHODS: This is a retrospective review of 30 consecutive
      patients 18 years or younger undergoing either bilateral staged or bilateral
      simultaneous thoracotomy between March 1994 and July 2004. Follow-up (mean, 47
      months) was available for all patients. RESULTS: Thirty patients (17 boys, 13
      girls; average age, 12 years) underwent bilateral staged or bilateral
      simultaneous thoracotomy. Eighteen patients underwent staged thoracotomy, 9
      patients underwent simultaneous thoracotomy, and 3 patients underwent both
      procedures. Diagnosis included sarcoma (n = 21), Wilms tumor (n = 4),
      indeterminate pulmonary nodules (n = 3), and germ cell tumor (n = 2). When we
      compared outcomes for patients undergoing simultaneous versus staged bilateral
      thoracotomy, mean hospital stay (5.2 vs 10.6 days; P < .002), intensive care unit
      stay (1 vs 2 nights; P < .0001), days with tube thoracostomy (4 vs 8 days; P <
      .0005), and time to initiation of adjuvant chemotherapy (13 vs 30 days; P < .05)
      were all significantly less for patients undergoing bilateral simultaneous
      thoracotomy. In addition, postoperative complications were less frequent in
      patients undergoing simultaneous versus staged thoracotomy (0 vs 3 events; P =
      .25). CONCLUSIONS: In selected patients, bilateral simultaneous thoracotomy is
      safe and may lessen morbidity and hospital stay while avoiding delay in
      initiation of adjuvant chemotherapy.

PMID- 16567171
TI  - Bilateral Wilms' tumors with progressive or nonresponsive disease.
AB  - BACKGROUND: To provide guidelines for future cooperative group trials, we
      reviewed the outcomes of children with bilateral Wilms' tumors (BWTs) treated on
      National Wilms Tumor Study-4 (NWTS-4) who had progressive or nonresponsive
      disease (PNRD). METHODS: NWTS-4 enrolled 3335 patients from August 1986 to
      September 1994 including 188 patients with BWT (5.6%). Treatment and outcome data
      were collected on patients with BWT. Treatment guidelines were outlined in the
      protocol, but patients were not on study. RESULTS: Thirty-eight children with BWT
      had PNRD. Preoperative chemotherapy was given for a median of 7 months (range, 2
      29 months) before definitive resection. After the initial chemotherapy regimen,
      36 children went on to a second regimen, and of these, 21 children received a
      third regimen before resection. Eleven patients received irradiation to one or
      both kidneys. Pathology at resection revealed previously undiagnosed anaplasia in
      3 patients (2 diffuse and 1 focal) treated for 14, 15, and 15 months before
      resection. A fourth patient developed a diffusely anaplastic tumor 13 months
      after therapy. Other pathological findings included rhabdomyomatous (4 patients)
      or differentiated stromal elements (10 patients) and complete necrosis (1
      patient). Ten kidneys from 7 patients lacked biopsy at presentation or pathology
      review of those specimens. CONCLUSIONS: BWT patients with PNRD received prolonged
      courses of chemotherapy. Early and sequential biopsies to establish the reason
      for failure to respond should be obtained. This will identify anaplastic tumors
      managed best by early nephrectomy and intensive chemotherapy and will also
      distinguish differentiated tumors that are best managed with early resection, but
      less intensive therapy after nephrectomy.

PMID- 16567172
TI  - Severe dysplasia in children with familial adenomatous polyposis: rare or simply
      overlooked?
AB  - BACKGROUND/PURPOSE: Because severe dysplasia and carcinoma in children with
      familial adenomatous polyposis (FAP) younger than 18 years is rare, earlier
      surgical intervention is not common. The purpose of this study is to report the
      prevalence of dysplasia and carcinoma among children with FAP in our institution.
      METHODS: From 1998 through 2004, children 18 years or younger with FAP that
      underwent total proctocolectomy at a large children's hospital were
      retrospectively reviewed. RESULTS: Eleven children underwent surgery for FAP. The
      mean age at surgery was 13 +/- 3.2 years. Approximately half of the patients who
      underwent preoperative endoscopy had evidence of dysplasia. Nine (82%) patients
      had dysplasia on preoperative biopsy and/or operative specimen, and 3 (27%) of
      these patients had severe dysplasia or carcinoma in situ. Four of the 5 patients
      without symptoms had evidence of dysplasia. No patients had invasive carcinoma.
      CONCLUSION: We observed a higher incidence of severe colonic dysplasia in young
      children with FAP compared with the current literature. A significant number of
      patients with dysplasia at surgery had no symptoms and no evidence of dysplasia
      on preoperative endoscopic biopsies. These data suggest that earlier intervention
      in children with FAP may be beneficial and should be investigated further.

PMID- 16567173
TI  - Extracorporeal membrane oxygenation for support of children after hematopoietic
      stem cell transplantation: the Extracorporeal Life Support Organization
      experience.
AB  - PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a means of respiratory and
      hemodynamic support for patients failing conventional therapies. Children
      requiring hematopoietic stem cell transplantation who develop complications
      during therapy may require ECMO. Such patients pose medical and ethical
      challenges for clinicians considering initiation of ECMO. The authors review the
      outcomes of these patients and propose recommendations. METHODS: The
      Extracorporeal Life Support Organization Registry was queried for all patients
      younger than 18 years with an International Classification of Diseases, Ninth
      Revision, or Current Procedural Terminology code related to bone or stem cell
      transplant. RESULTS: Nineteen children in the registry met inclusion criteria.
      The median age was 9.6 years (7 months to 17.5 years). Initiation of ECMO was for
      pulmonary support (n = 17), cardiac support (n = 1), or cardiopulmonary
      resuscitation (n = 1). The median duration of ECMO support was 5.1 days (range,
      30 hours to 42 days). Pulmonary infections included 3 parainfluenza, 2
      Pneumocystis carinii, 1 influenza A, and 1 respiratory syncytial virus. Overall,
      15 (79%) died during their ECMO run, whereas only 4 (21%) survived to come off
      ECMO. Furthermore, of those who survived their ECMO run, only one patient
      survived to discharge from the hospital. Risk factors for death on ECMO include
      development of renal complications and development of multiorgan dysfunction.
      CONCLUSION: Patients who require ECMO for cardiopulmonary support after
      hematopoietic stem cell transplantation have a poor prognosis. Clinicians must be
      cautious in presenting this option to parents and present them with appropriate
      expectations in this high-risk population.

PMID- 16567174
TI  - Corticosteroids for fetuses with congenital diaphragmatic hernia: can we show
      benefit?
AB  - BACKGROUND AND PURPOSE: Prenatal corticosteroids have been used in fetuses with
      congenital diaphragmatic hernia (CDH). We tested the utility of steroids by 2
      methods. METHODS: Mothers carrying fetuses with CDH were randomized to 3 weekly
      doses of betamethasone or placebo starting at 34 weeks. Patients were followed
      until death or discharge. In a separate cohort study, the CDH Registry was used
      to compare infants who received prenatal steroids to those who had not. RESULTS:
      Thirty-four patients were enrolled at 7 centers, with 32 completing the trial.
      There were 15 placebo and 17 steroid patients. There was no difference in
      survival, length of stay, duration of ventilation, or oxygen use at 30 days. For
      the cohort study, we looked at infants older than 34 weeks who were born after
      October 2000 when data on prenatal steroids were collected. There were 1093
      patients; 390 were evaluable, with 56 receiving steroids. There was no difference
      in survival, length of stay, ventilator days, or oxygen use at 30 days.
      CONCLUSION: Neither the trial nor the CDH Registry suggest that late prenatal
      corticosteroids benefit fetuses with CDH. More than 1700 mothers and fetuses
      would need to be enrolled in a trial to show a 10% improvement in survival. It is
      unlikely that late steroids offer benefit to most fetuses with CDH.

PMID- 16567175
TI  - Fetal tracheal reconstruction with cartilaginous grafts engineered from
      mesenchymal amniocytes.
AB  - BACKGROUND/PURPOSE: This study was aimed at determining whether cartilaginous
      grafts engineered from mesenchymal cells normally present in the amniotic fluid
      could be used in fetal tracheal repair. METHODS: Ovine mesenchymal amniocytes
      were expanded in culture, labeled with green fluorescent protein, and seeded onto
      biodegradable scaffold tubes maintained in chondrogenic medium. After
      chondrogenic differentiation of the constructs was confirmed, they were used to
      repair either partial or full circumferential tracheal defects in allogeneic
      fetal lambs (n = 7). Newborns were evaluated for signs of airway compromise.
      Implants were harvested over a 10-day period postnatally for multiple analyses.
      RESULTS: All 5 lambs that survived to term were able to breathe spontaneously at
      birth, 4 (80%) of them without stridor. However, variable degrees of stridor
      developed over time in all but one animal. Mild-to-moderate tracheal stenosis was
      present in all specimens. Histologically, grafts contained green fluorescent
      protein-positive cells, were lined with pseudostratified columnar epithelium, and
      remodeled into a predominantly fibrous cartilage pattern. Implants showed no
      significant changes in glycosaminoglycans, collagen, and elastin content at
      harvest. CONCLUSIONS: Engineered cartilaginous grafts derived from mesenchymal
      amniocytes may become a viable alternative for tracheal repair. The amniotic
      fluid can be a practical cell source for engineered tracheal reconstruction.

PMID- 16567176
TI  - Demonstrating relief of cardiac compression with the Nuss minimally invasive
      repair for pectus excavatum.
AB  - BACKGROUND/PURPOSE: Anatomic and physiological parameters have not been routinely
      used in the preoperative and postoperative evaluation of pectus excavatum. Most
      symptomatic patients have had significant subjective improvement after pectus
      correction. This study is based upon the use of noninvasive upright
      echocardiography/electrocardiogram (echo/EKG) with exercise to both identify and
      provide evidence of correction of cardiac abnormalities resulting from pectus
      excavatum. METHODS: One hundred twenty-three patients, 99 males and 24 females,
      ages 5 to 18 years (average, 13 years) underwent Nuss pectus repair. A
      retrospective review of their medical records was performed. RESULTS: Symptoms
      related to exertion were present in 106 (86%). The mean Haller chest wall index
      (CWI) was 4.3 (2.4-10.85). Preoperative echo/EKG with exercise revealed cardiac
      compression in 117 (95%). A mitral valve abnormality was present in 54 (44%). Six
      children had no chamber compression but mitral valve prolapse was present in 2
      and significant arrhythmias in 4. All patients were asymptomatic after surgery.
      Postoperative echo/EKG with exercise was performed in 107 (87%). The
      postoperative echo/EKG was normal in 100 (93% of those studied). Mild persistent
      mitral valve prolapse existed in 7. There were no postoperative arrhythmias.
      Twelve (9.8%) patients with low CWI (<3.25) were relieved of chamber compression
      and had no postoperative arrhythmia. Patent ductus was discovered in 2 patients
      on their postoperative echos. One closed spontaneously. A child with Marfan
      syndrome required interventional occlusion. CONCLUSION: Noninvasive echo/EKG with
      exercise is beneficial in the evaluation of patients with pectus excavatum and
      provides objective evidence of improvement postoperatively. It is especially
      valuable as a physiological indicator of cardiac abnormality in patients with a
      CWI below 3.25. Patients with mitral valve prolapse need long-term follow-up.

PMID- 16567177
TI  - Pediatric surgery fellowship compliance to the 80-hour work week.
AB  - OBJECTIVE: The goal of this study was to determine the compliance of pediatric
      surgery fellowships with Accreditation Council for Graduate Medical Education
      (ACGME) duty hour restrictions while confronting a reduced resident workforce.
      MATERIALS AND METHODS: An evaluation of training programs was performed by
      surveying pediatric surgery fellows on aspects of work hours, ACGME guideline
      compliance, operative case volume, employment of physician extenders, and
      didactic education. RESULTS: A 74% survey response rate was achieved. Of the
      respondents, 95% felt fully aware of ACGME guidelines. Although 95% of programs
      had mechanisms for compliance in place, only 45% of fellows felt compliant.
      Median work hours were 80 to 90 hours per week. Although subordinate residents
      were felt to obtain better compliance (>86%), only 69% of fellows perceived
      greater service commitment as a result. No impact on volume of operative cases
      was perceived. Of the programs, 89% employed physician extenders and 55% used
      additional fellows, but no overall effect on fellow work hours was evident.
      Fellows did not identify an improvement in the quality of clinical fellowships
      with guideline implementation. CONCLUSIONS: A minority of fellows comply with
      ACGME guidelines. Vigilance of duty hour tracking correlates to better
      compliance. A shift of patient care to fellows is perceived. Use of support
      personnel did not significantly aid compliance.

PMID- 16567178
TI  - A leap in faith: the impact of removing the surgeon from the level II trauma
      response.
AB  - BACKGROUND: Limitation of resident work hours has created the need to explore
      alternatives to surgeon presence during initial assessment and resuscitation for
      selected life-threatening injuries in children. We recently eliminated the
      requirement for surgeon presence during Level II alerts. The purpose of this
      study was to evaluate the impact of this change on patient care. METHODS: A
      retrospective analysis of trauma alert activity was performed using data from our
      trauma registry. In March 2003, responsibility for level II alerts was
      transferred from the pediatric surgeons (PSs) to the Emergency Department (ED)
      physicians. We compared the activity in the 18-month period before this change
      (period 1; n = 627) to that afterward (period 2; n = 587). Outcome measures
      included injury severity score, emergency department length of stay, missed
      injuries, abdominal computed tomography use, and mortality. Data were analyzed
      using log-rank statistic, chi2, or t test, where appropriate, with significance
      level at P < .05. RESULTS: During the entire study period, 1499 patients met the
      trauma alert activation criteria of which 1214 (81%) were level II alerts. The
      mean injury severity score for period 1 (8.5 +/- 7.3 SD) was similar to period 2
      (9.0 +/- 7.1 SD). When ED physicians replaced PS for Level II alerts, ED length
      of stay increased from 135 minutes to 165 minutes (P < .001). In addition, the
      use of abdominal computed tomography was significantly decreased (53.6% vs 42.6%;
      P < .001). However, there were no missed injuries and no significant differences
      in the rate of mortality. CONCLUSIONS: When ED physicians replaced PS for Level
      II alerts, trauma room length of stay was increased, but use of abdominal imaging
      was decreased with no differences in rate of missed injury or mortality.
      Emergency Department physicians can safely replace PS during Level II alerts.
      These findings may be useful to institutions experiencing surgical workforce
      limitations for trauma alerts.

PMID- 16567179
TI  - An analysis of proctoscopy vs computed tomography scanning in the diagnosis of
      rectal injuries in children: which is better?
AB  - BACKGROUND: Current dogma suggests that the diagnosis of rectal injury can be
      made after physical examination and proctoscopy (PR). However, anecdotal evidence
      suggests that these modalities lack specificity when applied to children and that
      computed tomography (CT) scanning may be superior. A direct comparison between CT
      scanning and PR has not been performed. We therefore sought to compare CT with PR
      in the diagnosis of rectal injury by analyzing our large institutional
      experience. METHODS: To assess institutional outcome, the charts of all children
      younger than 18 years admitted to our level I trauma center (1999-2004) were
      prospectively collected and retrospectively assessed. Demographics, diagnostic
      accuracy (PR vs CT), and outcome (length of stay, days in the intensive care unit
      [ICU], Injury Severity Score, and missed injury) were assessed. RESULTS: There
      were 24 injuries (63% boys, 71% blunt, 100% survival), and diagnostic modality
      included the following: PR, 37.5%; CT, 37.5%; laparotomy alone, 8%. Length of
      stay (PR 5.7 +/- 6.2 vs CT 13.7 +/- 22.2, NS) were similar between groups. Of the
      missed rectal injuries, 66% of patients undergoing PR had missed injuries that
      were ultimately detected by CT whereas 33% of the patients undergoing CT scan had
      a missed injury. CONCLUSION: CT is at least as accurate as PR in diagnosing
      pediatric rectal injury. Consideration of early scanning as opposed to PR may
      improve diagnosis and outcome in these patients.

PMID- 16567180
TI  - Management of giant omphalocele with rapid creation of abdominal domain.
AB  - BACKGROUND: The management of giant omphaloceles (GO) can be quite difficult when
      there is absence of abdominal domain. Coverage with delayed closure has been
      described. We present a technique to create an adequate peritoneal domain.
      METHODS: This is a retrospective review of our experience using an
      intraperitoneal tissue expander (IPTE) to create adequate abdominal domain in 2
      patients with GO. RESULTS: In 2 children with unrepaired GO, an IPTE was placed
      into the pelvis and was inflated to the target volume over 3 to 4 weeks. At the
      definitive operation for the closure of the abdominal defect, the IPTE was
      removed, allowing reduction of all the viscera into the peritoneal cavity and
      achieving complete abdominal wall closure. The patients are now 1 year
      postoperative, each having a normal abdomen and enjoying normal growth and
      development. CONCLUSION: Intraperitoneal tissue expander placement can create the
      needed domain over several weeks in GO. Its use in 2 cases was associated with
      satisfactory complete abdominal wall closure in short order. This technique
      should be considered as a treatment option.

PMID- 16567181
TI  - Video-assisted transumbilical appendectomy in children.
AB  - BACKGROUND: Video-assisted transumbilical appendectomy (VATA) is a combination of
      laparoscopic and open techniques and is not widely used in children. We are
      reporting our most recent experience with this technique. METHODS: After the
      institutional review board approval, the charts of patients who underwent VATA
      between December 2003 and October 2004 were retrospectively reviewed. All
      children presenting with a preoperative diagnosis of appendicitis were
      candidates. A 10-mm trocar was placed in the umbilicus. An operating laparoscope
      was used for mobilizing the appendix. The appendix was delivered through the
      umbilicus. A standard extracorporeal appendectomy was performed. The umbilical
      ring was closed and the wound irrigated. Demographic and outcome data were
      collected and is presented as mean +/- SD. RESULTS: Sixty-one males and 50
      females underwent VATA (n = 111). Age and weight were 11 +/- 3.2 years and 49 +/-
      22 kg, respectively. Six patients had previous abdominal surgery. Operative time
      was 36 +/- 24 minutes (range, 9-140 minutes). An additional trocar was placed in
      2 patients, and 2 patients were converted to open. Five patients had additional
      procedures. Appendicitis was classified intraoperatively as acute (n = 44),
      suppurative (n = 5), gangrenous (n = 8), ruptured (n = 30), appendiceal colic (n
      = 13), and other (n = 11). Preoperative antibiotics were given to 95 patients and
      were continued in 35 patients postoperatively. Length of stay was 1.8 +/- 1.7
      days (range, 1-11 days). Length of follow-up was 13 +/- 6.3 days (n = 90).
      Complications included intra-abdominal abscess (n = 1) and wound infection (n =
      7). CONCLUSIONS: Video-assisted transumbilical appendectomy minimizes equipment
      needs, thus, potentially reducing cost. Simple and complex appendectomies can be
      performed even if the patient has had previous abdominal surgery. Our
      complication rate was low, and our operating times and length of stay were short.
      Video-assisted transumbilical appendectomy is a safe and effective technique in
      children and can be used in lieu of the 3-trocar laparoscopic technique.

PMID- 16567182
TI  - Absent STAT-1 expression perturbs adaptation and apoptosis after massive
      intestinal resection.
AB  - BACKGROUND: We have previously established the significance of epidermal growth
      factor receptor (EGFR) activity and the cyclin-dependent kinase inhibitor
      p21waf1/cip1 (p21) for the adaptive response of the intestine to massive small
      bowel resection (SBR). In this study, we tested the role of the signal transducer
      and activator of transcription 1 (STAT-1) as this transcription factor is
      activated by the EGFR and known to induce p21 expression. METHODS: Control (n =
      40; C57/Bl6) and STAT-1-null mice (n = 40) underwent 50% proximal SBR or sham
      operation. After 3 days, the remnant ileum was harvested and the villus and crypt
      morphology was measured along with changes in rates of enterocyte proliferation
      and apoptosis. RESULTS: The magnitude of resection-induced adaptation was greater
      in STAT-1-null animals as verified by taller villi and deeper crypts. The
      expected increase in enterocyte apoptosis did not occur after SBR in the
      background of STAT-1 deficiency. Western blotting revealed elevated expression of
      p21 protein in both STAT-1-null and controls after SBR. CONCLUSION: Increased p21
      expression after SBR in the absence of STAT-1 suggests an alternate mechanism for
      resection-induced regulation of p21. Enhanced adaptation in STAT-1-null animals
      suggests that this transcription factor serves an inhibitor to the process of
      adaptation, perhaps via regulation of enterocyte apoptosis.

PMID- 16567183
TI  - Combined pharmacotherapy that increases proliferation and decreases apoptosis
      optimally enhances intestinal adaptation.
AB  - BACKGROUND: Adaptation after massive small bowel resection (SBR) is associated
      with increased rates of enterocyte proliferation (P) and apoptosis (A). In the
      present study, we sought to determine the effect of dual therapy designed to
      increase P and simultaneously reduce A. METHODS: C57Bl/6 mice underwent a 50%
      small bowel resection (SBR) or sham operation, and then received an inhibitor of
      apoptosis (pan-caspase inhibitor), a stimulus for proliferation (epidermal growth
      factor; EGF), a combination, or vehicle control. After 3 days, adaptive
      morphology (villus height, crypt depth) and rates of enterocyte turnover
      (proliferation and apoptosis) were measured in the remnant ileum. RESULTS:
      Adaptation in controls and treated with the inhibitor was similar. EGF-treated
      mice demonstrated an even greater adaptive response. Combined therapy with the
      inhibitor and EGF resulted in maximal adaptation as gauged by the greatest
      increases in villus height and crypt depth and ratio of rates of P to A.
      CONCLUSION: The capacity for adaptation following massive SBR is maintained via
      tight regulation of cell production and death. Pharmacologic intervention
      directed at increasing enterocyte proliferation while simultaneously decreasing
      apoptosis augments adaptation greater than either intervention alone and may
      provide a useful strategy to clinically amplify adaptation.

PMID- 16567184
TI  - Surgery for intestinal perforation in preterm neonates: anastomosis vs stoma.
AB  - BACKGROUND: Traditionally, a stoma is established after resection of perforated
      or necrotic intestine for isolated intestinal perforation (IIP) and necrotizing
      enterocolitis (NEC). We compared the outcome of resection and anastomosis (RA)
      with stoma formation (RS). METHODS: Sixty-eight neonates undergoing laparotomy
      for IIP (n = 20), NEC (n = 43), and indeterminate cause (n = 5) were reviewed
      retrospectively. Intestinal resection was followed by either anastomosis or
      stoma. The primary outcome measure was the frequency of anastomosis- and stoma
      related complications. RESULTS: The median gestational age (GA) was 28.5 weeks
      and birth weight (BW) was 940 g. Thirty-seven neonates had RA (NEC 22, IIP 14, 1
      unknown), 28 RS (NEC 21, IIP 6, 1 unknown), and 3 laparotomy only. Twenty-five
      neonates died postoperatively. The mean +/- SD GA of those who survived was 30 +/
      4.5 weeks and those who died was 27.2 +/- 3.5 weeks (P = .008). The mean BW for
      those that survived was 1440.5 +/- 865.1 g and those who died was 827.7 +/- 385.1
      g (P = .002). There was no statistically significant difference between the RA
      and RS groups for GA (P = .93), BW (P = .4), general complications (P = .96),
      anastomosis and stoma complications (P = .48), and deaths (P = .42). CONCLUSIONS:
      RA, rather than stoma, is an acceptable option in the surgical management of
      preterm neonates with IIP or NEC.

PMID- 16567185
TI  - Colonic manometry as predictor of cecostomy success in children with defecation
      disorders.
AB  - PURPOSE: The aim of this study was to define the predictive value of colonic
      manometry and contrast enema before cecostomy placement in children with
      defecation disorders. METHODS: Medical records, contrast enema, and colonic
      manometry studies were reviewed for 32 children with defecation disorders who
      underwent cecostomy placement between 1999 and 2004. Diagnoses included
      idiopathic constipation (n = 13), Hirschsprung's disease (n = 2), cerebral palsy
      (n = 1), imperforate anus (n = 6), spinal abnormality (n = 6), and anal with
      spinal abnormality (n = 4). Contrast enemas were evaluated for the presence of
      anatomic abnormalities and the degree of colonic dilatation. Colonic manometry
      was considered normal when high-amplitude propagating contractions (HAPC)
      occurred from proximal to distal colon. Clinical success was defined as normal
      defecation frequency with no or occasional fecal incontinence. RESULTS: Colonic
      manometry was done on 32 and contrast enema on 24 patients before cecostomy. At
      follow-up, 25 patients (78%) fulfilled the success criteria. Absence of HAPC
      throughout the colon was related to unsuccessful outcome (P = .03). Colonic
      response with normal HAPC after bisacodyl administration was predictive of
      success (P = .03). Presence of colonic dilatation was not associated with colonic
      dysmotility. CONCLUSION: Colonic manometry is helpful in predicting the outcome
      after cecostomy. Patients with generalized colonic dysmotility are less likely to
      benefit from use of antegrade enemas via cecostomy. Normal colonic response to
      bisacodyl predicts favorable outcome.

PMID- 16567186
TI  - Basic fibroblast growth factor and granulocyte colony-stimulating factor enhance
      mucosal surface expansion after adult small bowel transplantation without
      vascular reconstruction in rats.
AB  - AIM: We showed previously that adult small bowel could be transplanted
      successfully in rats without vascular reconstruction by removing the graft
      serosa. In this study, we assessed if granulocyte colony-stimulating factor (G
      CSF) or basic fibroblast growth factor (bFGF) could improve graft survival in the
      same rat model. METHOD: A 10-mm-long adult small bowel graft from an adult 12
      week-old Lewis rat was transplanted into a pouch created in the omentum of a 5
      week-old Lewis rat (syngeneic bowel transplantation [SBTx], n = 49). Graft serosa
      was removed just before SBTx in the serosectomy group (n = 29) and left intact in
      the nonserosectomy group (n = 20). Each group was divided into 3 subgroups (sG):
      sG-1 had no G-CSF or bFGF; sG-2 had daily subcutaneous injections of G-CSF; and
      sG-3 had continuous infusion of bFGF around the graft in the omentum. All grafts
      were harvested 14 days after SBTx and studied histologically. A mucosal surface
      expansion score (MSES) was used where 0 = no mucosa on the graft, 1 = mucosa on
      one fourth of the graft, 2 = mucosa on one half of the graft, 3 = mucosa on three
      fourths of the graft, and 4 = mucosa on the whole graft. The density of CD34
      positive capillaries per 1000 nuclei was also measured. RESULTS: Serosectomy
      group MSES were significantly higher than nonserosectomy group MSES indicating
      that grafts survived (P < .0001). CD34-positive capillaries in serosectomy group
      subgroups for mucosa were 103.9 +/- 34.2, 130.2 +/- 52.0, and 132.3 +/- 37.7,
      respectively; for muscle, 74.4 +/- 38.0, 86.2 +/- 32.9, and 82.4 +/- 30.3,
      respectively; and for omentum, 73.8 +/- 30.1, 151.3 +/- 60.3, and 140.0 +/- 49.0,
      respectively. Mucosal surface expansion score and overall CD34-positive
      capillaries for sG-2 and sG-3 were significantly higher than for sG-1 (both, P <
      .05). CONCLUSION: Our results suggest that G-CSF and bFGF enhance angiogenesis
      and mucosal surface expansion.

PMID- 16567187
TI  - Heparin-binding epidermal growth factor-like growth factor reduces intestinal
      apoptosis in neonatal rats with necrotizing enterocolitis.
AB  - PURPOSE: We have previously demonstrated that enterally administered heparin
      binding epidermal growth factor-like growth factor (HB-EGF) decreases the
      incidence and severity of necrotizing enterocolitis (NEC) in a neonatal rat
      model. Because apoptosis contributes to gut barrier failure in this model, the
      aim of this study was to investigate the effect of HB-EGF on apoptosis during the
      development of NEC. METHODS: NEC was induced in neonatal rats by exposure to
      hypoxia, hypothermia, hypertonic formula feeding (HHHTF) plus enteral
      administration of lipopolysaccharide (LPS). Fifty-one neonatal rats were randomly
      divided into the following groups: (1) breast-fed (BF), (2) HHHTF + LPS, and (3)
      HHHTF + LPS with HB-EGF (600 microg/kg) added to the formula. NEC was evaluated
      using a standard histological scoring system. Apoptotic cells in intestinal
      tissues were detected by terminal deoxynucleotidyltransferase-mediated dUTP nick
      end labeling (TUNEL) and by active caspase 3 immunohistochemical staining.
      RESULTS: The incidence of NEC in the HHHTF + LPS group was higher than that in
      the BF group (65% vs 0%, P < .05). With administration of HB-EGF, the incidence
      of NEC significantly decreased to 23.8% (P < .05). The median TUNEL and active
      caspase 3 scores in the HHHTF + LPS group were higher than those in the BF group
      (1.9 vs 0.9 and 1.75 vs 0.6, respectively, P < .05). The median TUNEL and active
      caspase 3 scores were significantly decreased in the HHHTF + LPS + HB-EGF group
      compared with the HHHTF + LPS group (1.24 vs 1.9 and 1.0 vs 1.75, respectively, P
      < .05). CONCLUSION: HB-EGF reduces the incidence of NEC in a neonatal rat model
      in part by decreasing apoptosis. These results support the use of HB-EGF-based
      clinical regimens for the treatment of NEC.

PMID- 16567188
TI  - Colostomy in anorectal malformations: a procedure with serious but preventable
      complications.
AB  - PURPOSE: Colostomy for patients with anorectal malformations decompresses an
      obstructed colon, avoids fecal contamination of the urinary tract, and protects a
      future perineal operation. The procedure is associated with several significant
      complications. MATERIALS AND METHODS: The medical records of 1700 cases of
      anorectal malformations were retrospectively reviewed. A total of 230 patients
      underwent reconstruction without a colostomy. Of the remaining 1470 patients,
      1420 had their colostomy performed at another institution (group A) and 50 did at
      our institution (group B) using a specific technique with separated stomas in the
      descending colon. RESULTS: There were 616 complications identified in 464
      patients of group A and in 4 patients in group B, an incidence of 33% vs 8% (P <
      .01). Complications in group A were classified into several groups. The first
      group was mislocation (282 cases), including 116 with stomas too close to each
      other, 97 with stomas located too distally in the rectosigmoid (which interfered
      with the pull-through), 30 with inverted stomas, 21 with stomas too far apart
      from each other, and 18 with right upper sigmoidostomies. The second largest
      group was prolapse (119 cases), which occurred mainly in mobile portions of the
      colon. The third group was composed of general surgical complications after
      colostomy closure (82 cases), such as intestinal obstruction (47 cases), wound
      infection (13 cases), incisional hernia (11 cases), anastomotic dehiscence (7
      cases), sepsis (3 cases), and bleeding (1 case). Two of the septic patients died.
      Another group included 62 patients who received a Hartmann's procedure, which we
      considered to be contraindicated in anorectal malformations. A total of 42
      patients suffered from stenosis of the stoma; 29, from retraction. CONCLUSIONS:
      Most colostomy complications are preventable using separated stomas in the
      descending colon. Mislocated stomas lead to problems with appliance application,
      interference with the pull-through, megasigmoid, distal fecal impaction, and
      urinary tract infections. Loop colostomies lead to urinary tract infections,
      distal fecal impaction, and prolapse. Prolapse is a potentially dangerous
      complication that mostly occurs when the stoma is placed in a mobile portion of
      the colon. Recognizing this makes the complication preventable by trying to
      create colostomies in fixed portions of the colon or by fixing the bowel to the
      abdominal wall when necessary. The trend to avoid colostomies is justified;
      however, colostomy is the best way to prevent complications in anorectal surgery
      and, when indicated, should be done with a meticulous technique following strict
      rules to avoid complications.

PMID- 16567189
TI  - Extracellular matrix dynamics associated with tissue-engineered intravascular
      sclerotherapy.
AB  - BACKGROUND: The extracellular dynamics after intravascular sclerotherapy with an
      injectable, fibroblast-based engineered construct is unknown. METHODS: Rabbits
      underwent ethanol sclerotherapy of a jugular vein segment. Control animals (n =
      40) underwent no further treatment or an acellular collagen hydrogel was
      injected. Experimental animals (n = 20) received a tissue-engineered construct.
      After 1, 2, 4, and 20 to 24 weeks, segments were evaluated for collagen,
      glycosaminoglycan (GAG), matrix metalloproteinase (MMP) 2 and 9, and tissue
      inhibitors of MMP (TIMPs) 1 and 2 and scored on a scale of 0 to 3. Groups and
      time points were compared using nonparametric statistical analysis. RESULTS:
      Collagen content was higher in animals that received fibroblasts (P < .05).
      Glycosaminoglycan analysis showed a higher grade only at 1 week (P < .05).
      Collagen and GAG deposition were prominent at weeks 1 through 4, and decreased
      over time. Both MMP-2 and MMP-9 and TIMP-1 and TIMP-2 grade decreased with time
      (P < .01) in all groups, with no differences between groups. CONCLUSION:
      Enhancement of intravascular sclerotherapy by tissue engineering stems, at least
      in part, from increased local deposition of collagen and GAG. MMP and TIMPs may
      play a role in recanalization after experimental sclerotherapy. Tissue
      engineering may be a valuable adjunct for the treatment of vascular
      malformations.

PMID- 16567190
TI  - Distension enterogenesis: increasing the size and function of small intestine.
AB  - INTRODUCTION: The purpose of this study is to evaluate the feasibility of using
      saline infusion to lengthen small bowel while preserving intestinal enzymatic
      function. METHODS: Male Sprague-Dawley rats had a 3-cm jejunal segment taken out
      of continuity. A catheter was inserted in the proximal end, and the distal end
      was oversewn. Continuous infusion of saline into the isolated jejunal segment was
      started 2 weeks postoperatively. Segments were harvested 1 week later. Segment
      weights and lengths were measured preoperatively and at the time of harvest.
      Histology of harvested segments was performed. Alkaline phosphatase (ALP) and
      lactase assays were performed. Comparisons were made with normal jejunum from
      control animals. RESULTS: A 32% increase in length was achieved with saline
      distension of small intestine. The segment weight to length ratio was
      significantly increased by saline distension; however, the total protein-to
      weight ratio was unchanged. Specific activities of ALP and lactase were not
      affected by saline distension. Because of the increased length and weight of the
      distended jejunal segments, total segment activities for both enzymes were
      significantly increased. CONCLUSIONS: Saline infusion appears to be a viable
      method for increasing small intestinal length without compromising enzymatic
      function. This phenomenon may provide a new method for the treatment of patients
      with short bowel syndrome in the future, and further study is warranted.

PMID- 16567191
TI  - Feasibility of magnetic resonance spectroscopy for evaluating fetal lung
      maturity.
AB  - BACKGROUND/PURPOSE: Amniocentesis is an invasive procedure with inherent risks.
      Magnetic resonance (MR) spectroscopy is a safe noninvasive way of measuring
      levels of choline-containing compounds (including surfactant) and other
      metabolites. The purpose of this study was to test the feasibility of assessing
      fetal lung maturity in vivo and ex vivo using MR spectroscopy to determine
      differences in amniotic fluid choline concentrations between the second and third
      trimesters. METHODS: Magnetic resonance spectroscopy was performed on ex vivo
      samples of amniotic fluid from second- and third-trimester fetuses. In vivo MR
      spectroscopy was performed on amniotic fluid and fetal lungs in third-trimester
      fetuses. Spectral acquisition and analysis were performed by an attending
      radiologist in conjunction with an MR spectroscopist. RESULTS: Choline-containing
      compounds were observed from 3.20 to 3.25 ppm. Comparison of spectra from second-
      and third-trimester amniocentesis revealed a trend toward increased choline at
      later gestational ages. Spectra from amniotic fluid and lungs of a third
      trimester fetus showed that choline can be detected in the in vivo setting.
      CONCLUSIONS: Magnetic resonance spectroscopy is a safe noninvasive procedure that
      enables measurement of choline-containing compounds in fetal lung and amniotic
      fluid. Magnetic resonance spectroscopy shows a trend toward an increased quantity
      of choline in third- vs second-trimester amniocentesis.

PMID- 16567192
TI  - Tracheal occlusion in fetal rats alters expression of mesenchymal nuclear
      transcription factors without affecting surfactant protein expression.
AB  - BACKGROUND/PURPOSE: Mesenchymal nuclear transcription factors (MNTF) are involved
      in lung development and maturation and regulate surfactant protein (SP)
      expression. Prolonged (>2 weeks) fetal tracheal occlusion (TO) has been shown to
      accelerate lung growth and inhibit pulmonary surfactant synthesis. The effects of
      TO on SP expression and MNTF, however, have not been formally assessed. The
      objectives of this study were to evaluate the effects of short-term (3 days) TO
      on normal lung growth and protein expression of pulmonary MNTF involved in SP
      synthesis. METHODS: At E19 (term, 22 days), 2 fetuses per time-dated Sprague
      Dawley rats underwent either TO (n = 23) or a sham (n = 22) operation. Lungs were
      harvested 72 hours post surgery. Pulmonary SP-A; SP-B; SP-C messenger RNA (mRNA)
      expression; and SP-A and SP-B, Hoxb5, thyroid transcription factor 1, and
      retinoic X receptor-alpha protein expression were analyzed. RESULTS: Lung weight
      was significantly increased by TO (TO 0.32 +/- 0.02g vs SHAM 0.14 +/- 0.01 g; P <
      .001), resulting in 123% increase of the lung-to-body-weight ratio. No difference
      of SP-A-mRNA (177 +/- 4.3 TO vs 169 +/- 4.4 SHAM; P = .25), SP-B-mRNA (87.7 +/-
      0.2 TO vs 87.4 +/- 0.02 SHAM; P = .33), and SP-C-mRNA (186.5 +/- 3.2 TO vs 183.2
      +/- 2.7 SHAM; P = .45) expression was found. Surfactant protein A (175.6 +/- 25.3
      TO vs 192.5 +/- 19.8 SHAM; P = .59) and SP-B (163.4 +/- 5.2 TO vs 166.8 +/- 9.3
      SHAM; P = .75) protein expression were similar in both groups; however, Hoxb5
      (70.3 +/- 18.9 TO vs 130.6 +/- 5.1 SHAM; P = .02) and thyroid transcription
      factor 1 (102.6 +/- 19 TO vs 181.1 +/- 6.3 SHAM; P = .007) expression were
      significantly decreased. Retinoic X receptor-alpha expression tended to be
      increased by TO (171.9 +/- 6.0 TO vs 155.4 +/- 6.7 SHAM; P = .06). CONCLUSIONS:
      Short-term TO late in gestation induces rapid lung growth. Surfactant protein
      mRNA and protein expression are not significantly altered. Thyroid transcription
      factor 1 and Hoxb5 are down-regulated by TO, suggesting that duration and timing
      of occlusion are important in balancing the effects of TO on lung growth vs lung
      maturation.

PMID- 16567193
TI  - Effect of VEGF on the branching morphogenesis of normal and nitrofen-induced
      hypoplastic fetal rat lung explants.
AB  - PURPOSE: Changes in vascular structures as well as vascular endothelial growth
      factor (VEGF) downregulation have been reported in hypoplastic lungs associated
      with congenital diaphragmatic hernia. We hypothesized that VEGF may accelerate
      branching morphogenesis and thus may modulate lung growth in normal and nitrofen
      induced pulmonary hypoplastic lungs. METHODS: A hypoplastic fetal lung model and
      a normal control lung model were induced by feeding pregnant rats with or without
      nitrofen, respectively. Fetal lungs harvested on day 13.5 were cultured at
      ambient oxygen tensions for 72 hours with 0, 25, 50, or 100 ng/mL of exogenous
      rat VEGF added daily in the serum-free medium. The rates of increase in bud count
      and airway contour were evaluated. Real-time polymerase chain reaction was
      carried out to evaluate the expression of surfactant protein C mRNA in the
      explants at the end of culture. RESULTS: Vascular endothelial growth factor
      accelerated the increase in bud count and airway contour in normal and
      hypoplastic lung explants compared to controls. Surfactant protein C mRNA
      expression was significantly increased at 50 ng/mL VEGF compared to controls in
      both normal and hypoplastic lung explants. CONCLUSION: These data suggest that
      VEGF plays an important role in lung morphogenesis and may accelerate lung growth
      in nitrofen-induced hypoplastic lung.

PMID- 16567194
TI  - Development of a model system for preliminary evaluation of tissue-engineered
      vascular conduits.
AB  - BACKGROUND/PURPOSE: The ability to construct tissue-engineered neovessels for use
      as arterial or venous grafts holds great promise for the advancement of pediatric
      surgical disciplines. Although the feasibility of tissue engineering vascular
      grafts has been demonstrated, the long-term function, safety, and efficacy of
      these grafts as well as their capacity to grow and adapt remain largely unknown.
      In an attempt to further characterize and develop this technology, we used severe
      combined immunodeficiency beige (SCID/bg) mouse recipients, chosen because such
      animals accept xenogenic human cells, to create a small animal model that would
      allow a rapid and cost-effective preliminary evaluation of the function of tissue
      engineered vascular grafts. METHODS: Eight CB-17 SCID/bg female mice underwent
      vascular graft placement. Four of these mice received aortic interposition
      grafts, 1 mouse received an inferior vena cava interposition graft, and 3 mice
      underwent aortocaval graft insertion. All grafts were fashioned from
      decellularized ovine arteriole tissue engineering scaffolds. Grafts were
      evaluated for patency using clinical examination, ultrasound interrogation, and
      micro-computed tomography. Animals were killed at various time points after
      implantation, and grafts were harvested and analyzed histologically using
      standard hematoxylin and eosin staining. RESULTS: All grafts were patent based on
      clinical examination for up to 35 days. Patency was confirmed in 5 grafts using
      ultrasound interrogation. Patency was confirmed in 4 grafts using micro-computed
      tomography. One animal that underwent arteriovenous grafting had to be euthanized
      secondary to high-output cardiac failure on postoperative day 2. The remaining
      animals were killed between postoperative days 12 and 35. Histologic evaluation
      of the specimens demonstrated patent grafts with cellular ingrowth into the
      tissue engineering scaffold. CONCLUSIONS: From these results, we conclude that
      the use of the SCID/bg mouse model for preliminary evaluation of new tissue
      engineering methodologies for construction of vascular conduits is feasible. Use
      of this model has the added advantage of evaluating nonautologous and even
      xenograft tissues, including human cells.

PMID- 16567196
TI  - Comparison between ureteral replacements using a transverse tubularized colonic
      tube or ileal ureter: experimental study in dogs.
AB  - INTRODUCTION: We report the comparison between ureteral replacements using a
      transverse tubularized colonic tube or ileal ureter in dogs. MATERIALS AND
      METHODS: Ten canines were studied. Four underwent ureteral substitution with an
      ileal ureter; 5 with a single transverse tubularized colonic tube and 1 with a
      double colonic transverse tubularized tube. The animals were observed for a
      predetermined interval of 30 days. At 30 days, the animals underwent an
      intravenous pyelogram, cystogram, urine analysis, and serum electrolyte sampling,
      and the kidney, ureteral conduit, and bladder were examined grossly and
      histologically. RESULTS: The pyelograms of both the ileal ureter and the
      transverse tubularized colonic tube showed prompt bilateral renal excretion.
      Grade 1 hydronephrosis was seen in 3 of 4 animals that received the ileal ureter
      and with 1 of 5 animals that received the colonic tube. Histological exam of the
      kidneys showed small focal areas of pyelonephritis in both groups without
      significant injury to the collecting tubules or glomeruli. DISCUSSION: The
      transverse tubularized colonic tube is an effective form of ureteral replacement
      in the animal model. The advantages of using the colon include its proximity to
      the ureters, the minimal mobilization needed, position outside the radiation
      portals, and the short colonic segment necessary.

PMID- 16567195
TI  - Laboratory parameters predictive of developing necrotizing enterocolitis in
      infants born before 33 weeks of gestation.
AB  - PURPOSE: The aim of this study was to identify laboratory findings predictive of
      necrotizing enterocolitis (NEC). METHODS: Prospective follow-up of 140 infants of
      less than 33 weeks of gestation. Twenty-six infants developed NEC (grades I to
      III, criteria of Bell et al [Ann Surg 1978;187:1-7]) (NEC group). For each, 2
      birth-weight, gestational age- and postnatal age-matched controls were selected
      (control group). Blood counts, glucose and electrolyte levels, C-reactive
      protein, and acid-base balance 3 days, 2 days, and 1 day before and at the onset
      of NEC and at corresponding ages from the controls were recorded. RESULTS:
      Metabolic acidosis occurred, the platelet levels decreased, and the blood glucose
      increased on successive days in the infants with grade NEC II-III. At the onset
      of NEC, the infants had significantly lower platelet and higher blood glucose
      levels compared with controls. More than half of infants with intestinal
      perforation had leukocyte levels above 30 x 10(9)/L and pH less than 7.25, and
      their mean blood glucose levels increased to more than 1.5 mmol/L in 24 hours.
      The remaining parameters were not useful. CONCLUSION: A persistent metabolic
      acidosis, decreasing platelet, and increasing blood glucose level on several
      successive days might predict a developing NEC, and leukocyte values above 30 x
      10(9)/L, pH less than 7.25, and a blood glucose rise by 1.5 mmol/L or more within
      24 hours predict NEC with intestinal perforation. Such findings should alert the
      physician to look for signs of NEC in a preterm infant.

PMID- 16567197
TI  - Congenital intestinal anomalies, neonatal short bowel syndrome, and
      prenatal/neonatal counseling.
AB  - BACKGROUND: Short bowel syndrome (SBS) is a severe malabsorption caused by bowel
      loss. Congenital intestinal anomalies (CIA) detectable by prenatal ultrasound as
      jejunoileal atresia, meconium peritonitis, complicated meconium ileus, and fetal
      volvulus can be responsible for SBS. AIMS: This study aims to investigate either
      frequency of SBS or the morbidity in CIA population during the first admission.
      MATERIAL AND METHODS: Records of CIA treated from 1997 to 2003 were reviewed. The
      prenatal ultrasound findings were correlated with SBS. Student's t and chi(2)
      tests were performed to analyze epidemiological data, growth at discharge,
      sepsis, liver disease, catheter-related complications, motor developmental delay,
      and hospital stay in CIA with and without SBS. RESULTS: Forty-four CIA: SBS
      developed in 43%, ranging from 83% in volvulus to 0% in complicated meconium
      ileus. Thirty-six prenatal diagnoses: a strong correlation with SBS was observed
      in isolated dilated bowel (58%). In SBS neonates, birth weight, gestational age,
      and growth at discharge were statistically lower, whereas sepsis, motor delay,
      and hospital stay were statistically higher. CONCLUSIONS: Many neonates with CIA
      detectable by prenatal ultrasound develop SBS. Short bowel syndrome presents a
      significant higher morbidity. The counseling should stress the frequent
      association between CIA and SBS as well as the significant morbidity in SBS.

PMID- 16567198
TI  - Hepatolithiasis after hepatic portoenterostomy for biliary atresia.
AB  - BACKGROUND: Hepatolithiasis after hepatic portoenterostomy for biliary atresia
      has been paid little attention, with only 22 reported cases. PATIENTS AND
      METHODS: Fifteen patients underwent living-related liver transplantation for
      biliary atresia after hepatic portoenterostomy in our hospital between 1998 and
      2004. The resected livers were examined for the existence and location of
      hepatolithiasis, composition of the calculi, and bacterial infection of bile. The
      relation between a history of cholangitis and the presence of hepatolithiasis was
      analyzed. RESULTS: Intrahepatic calculi were found in 8 (53%) of 15 patients. The
      calculi consisted of almost 100% calcium bilirubinate. Calculi were found in bile
      lakes in 8 patients. Bacteria were present in the bile in 8 (53%) of the 15
      patients. Of the 8 patients, 7 (88%) had a history of ascending cholangitis.
      CONCLUSIONS: Hepatolithiasis occurs after hepatic portoenterostomy for biliary
      atresia more frequently than previously thought. Bile stasis and possibly bile
      infection are the main causes of calculi formation.

PMID- 16567199
TI  - Extrahepatic portal vein morphology in children with extrahepatic portal
      hypertension assessed by 3-dimensional computed tomographic portography: a new
      etiology of extrahepatic portal hypertension.
AB  - BACKGROUND/PURPOSE: The cause of extrahepatic portal hypertension in children has
      not been clarified. Our aim was to determine the morphological features of the
      extrahepatic portal vein in children with extrahepatic portal hypertension by 3
      dimensional computed tomographic portography and to clarify the etiology of this
      disorder. MATERIALS AND METHODS: Six patients ranging in age from 10 to 18 years
      (median age, 12.8 years) who had portal hypertension presented with hematemesis.
      They underwent intravenous computed tomographic portography using a helical
      computed tomography scanner and 3-dimensional image reconstruction. RESULTS: The
      extrahepatic portal vein was visualized in all patients by 3-dimensional computed
      tomographic portography. None of the patients showed extrahepatic portal vein
      obstruction or cavernous transformation. All patients had a tortuous eta-shaped
      extrahepatic portal vein, and a line could be drawn through the flexures of the
      portal vein to the hepatic hilum. CONCLUSION: In children, extrahepatic portal
      hypertension is not caused by extrahepatic portal vein obstruction and may be of
      embryological origin.

PMID- 16567200
TI  - A report of 6 children with small bowel intussusception that required surgical
      intervention.
AB  - BACKGROUND/PURPOSE: We aim to justify the need for surgical intervention in our
      patients with childhood small bowel intussusceptions (SBIs) and review the
      current concepts in childhood SBI. MATERIALS AND METHODS: We retrospectively
      reviewed the clinical charts of all patients with surgically confirmed SBI
      between July 1999 and October 2002. Demographic data, clinical presentation and
      investigations, operative and pathologic findings, and outcome were analyzed.
      RESULTS: Of 173 patients with intussusception, 6 (3.5%) were diagnosed with SBI.
      Median age was 11 months. Ultrasonography revealed intussusceptions in all
      patients, but only 1 was diagnosed with SBI. Air enema reductions were attempted
      in 4 of 6 patients with all ending up in failure and surgery. Surgery revealed
      ileoileal intussusceptions in 4 patients and jejunojejunal intussusceptions in 2
      patients. Two patients had long intussusceptions measuring between 30 and 50 cm
      in length. Five patients had pathologic lead points, and bowel complications
      occurred in 2 patients. All underwent bowel resection and primary anastomosis.
      CONCLUSION: Despite reports on spontaneous reduction of SBI, surgery was
      unavoidable in all our patients with SBI because of the presence of pathologic
      lead points and/or bowel complications. Air enema reduction was ineffective in
      SBI. Due caution should be exercised when selecting patients for expectant
      management.

PMID- 16567201
TI  - Effect of paralysis of the abdominal wall muscles by botulinum A toxin to
      intraabdominal pressure: an experimental study.
AB  - PURPOSE: To show the effect of botulinum A toxin-induced paralysis of abdominal
      muscles on intraabdominal pressure. MATERIAL AND METHODS: Fifteen Sprague-Dawley
      rats were divided into 2 groups. An abdominal skin incision was done, and 2
      catheters were placed for the pressure monitoring and saline infusion. Saline
      solution was given to the abdomen until reaching to a pressure level of 9 cm H2O
      and 6 mm Hg in pressure device, and the amounts of injected saline were recorded.
      Then intraabdominal saline was drained. Two milliliters (5 U/mL) botulinum A
      toxin was applied to the abdominal muscles in group 2. Saline was injected at the
      same points in same amounts in group 1. After 3 days, catheters were placed, and
      the saline volumes needed to obtain the same pressure levels were recorded for
      each rat. Spontaneous motor unit potential (MUP), single MUP analysis and
      interference patterns of the muscles, respiratory rates, and vascular pressure
      measurements were recorded before and after botulinum toxin (Botox) injections.
      RESULTS: Mean intraabdominal saline volumes in the first and third days were 63.8
      and 64.4 mL in group 1 and 67.6 and 80.6 mL in group 2, respectively. Mean MUP
      amplitude and duration of the rectus muscles in group 2 (17.1 microV and 1.47
      milliseconds) were significantly lower than those of group 1 (187 microV and 4.9
      milliseconds) in the third day. There were no pathological changes in respiratory
      rates and pressure measurements before and after Botox injections. CONCLUSION:
      This pilot experimental study showed that local injection of botulinum A toxin
      causes paralysis in abdominal wall muscles, increases the intraabdominal volume,
      and decreases the pressure, and this application may be used as an adjunct in
      abdominal wall closure in selective cases.

PMID- 16567202
TI  - False-positive rate in prenatal diagnosis of surgical anomalies.
AB  - BACKGROUND/PURPOSE: Technical refinements and increasingly sophisticated
      equipment have led to higher sensitivity in prenatal diagnosis of congenital
      malformations; however, such progress may be accompanied by decreased
      specificity. The aim of this study is to evaluate evolution of prenatal diagnosis
      from the first sonographic suspicion of fetal anomaly until after delivery
      (diagnosis confirmed, resolution before birth, healthy baby, or affected with
      different disorder) to document rate of false-positive (FP) results. METHODS:
      Retrospective review of prenatal ultrasound examinations performed at our
      institution between 2000 and 2002 was conducted. The series includes pregnancies
      referred to our department after detection of thoracic and abdominal anomalies at
      routine obstetrical sonography and with a follow-up comprising at least the first
      6 months of life. Urologic malformations were excluded. Those fetuses who proved
      healthy at birth were considered FP results. RESULTS: One hundred fifty-seven
      fetuses/neonates underwent complete follow-up. Prenatal diagnosis of esophageal
      atresia resulted in 3 (27%) of 11 FPs. Finding of dilated bowel, isolated or
      associated with hyperechogenicity or ascites, was not predictive of small bowel
      obstruction in 7 (41%) of 17 fetuses. No FPs were found with regard to abdominal
      wall defects (8 gastroschisis and 26 omphaloceles, all confirmed at birth).
      Concerning thoracic malformations, no FPs were seen among the 28 cases of
      congenital diaphragmatic hernia, whereas diagnosis of lung malformation presented
      a specificity of 97% (1/28 FP). Ovarian cysts accounted for an FP rate of 17%
      (4/23 FPs). Overall, a percentage of FP of 12% (6/50) was seen in 2000, of 11%
      (5/44) in 2001, and 9% (6/63) in 2002, with no statistically significant
      difference. CONCLUSIONS: Because of the high FP rate regarding some particular
      anomalies, unnecessary psychological burden to prospective parents may ensue.
      This issue should be dealt with in future prospective studies.

PMID- 16567203
TI  - Increased expression of c-fos and c-jun in the rat small intestinal epithelium
      after ischemia-reperfusion injury: a possible correlation with the proliferation
      or apoptosis of intestinal epithelial cells.
AB  - BACKGROUND AND PURPOSE: An increased expression of immediate early genes, such as
      the c-fos and c-jun, is observed in some organs after ischemia-reperfusion (I/R)
      injury. These factors have been revealed to potentially induce apoptosis and
      proliferation of the postischemic cells. The purpose of this study is to analyze
      the relationship between the expression patterns of such immediate early genes
      and the cellular responses in the intestinal epithelial cells (IECs) after I/R
      stress. METHODS: The rat small intestine was reperfused after 30 minutes
      ischemia. Semiquantitative reverse transcription-polymerase chain reaction was
      used to quantify c-fos and c-jun messenger RNAs. The proliferation and apoptosis
      of IECs were detected by immunohistochemistry and the in situ terminal
      deoxynucleotidyl transferase-mediated dUTP biotin nick-end labeling method,
      respectively. RESULTS: The messenger RNA levels of the c-fos and c-jun showed
      characteristic patterns in the IECs after the I/R stress. The proliferation of
      the cells was initially observed after the I/R stress, followed by apoptosis of
      the cells. CONCLUSIONS: The sequential expression patterns of these factors are
      possibly related to the proliferation and apoptosis of the IECs.

PMID- 16567204
TI  - Follow-up of anorectal anomalies: the Italian parents' and patients' perspective.
AB  - BACKGROUND: Several studies addressed the long-term follow-up of anorectal
      anomalies (ARM) in relation to clinical issues (eg, continence) and quality of
      life. However, most of these studies are based upon questionnaires designed by
      physicians and/or health-care professionals, which may be sources of bias.
      METHODS: To investigate whether parents of children (patients themselves or older
      children or adults) who were born with ARM had the perception that they received
      appropriate care and follow-up, a survey was carried out in Italy, in 2003, among
      families with children with ARM. A 20-item questionnaire was mailed to 425
      patients and parents listed in the AIMAR (Italian association for anorectal
      malformation) database and was returned by 209 families. The questionnaire
      covered different aspects of ARM: type of malformations and surgery, associated
      anomalies, fecal and urinary continence, as well as aspects about information
      given to the parents and satisfaction of care and follow-up received. RESULT: The
      patients and parents demonstrated a good understanding of distribution of
      malformations and their anatomical classification; nevertheless, 67% of
      responders had to travel outside their living area for surgery. Bowel management
      (BM) was commonly used among subjects; however, a significant percentage of
      patients using regular enemas were still soiling (58 patients were clean and 116
      soiled). Urinary continence problems were mostly found in females with cloaca;
      nevertheless, 21 male patients reported occasional dribbling of difficult
      interpretation. Most subjects were provided with a good explanation about their
      or their child's malformation at time of reconstructive surgery, but the same
      level of information was missing about functional prognosis later in life when
      the need of an appropriate psychologic support was also felt. CONCLUSIONS:
      Patients and parents born with ARM are generally satisfied with the information
      received and with the short-term postreconstructive follow-up care. At longer
      follow-up, although more than a quarter of patients are completely clean, there
      is a significant percentage of subjects who still soil while following a BM
      program. This is explained by the small number of nurses and BM specialists who
      are involved in the rehabilitation process and by the lack of appropriate
      information about functional prognosis that are conveyed to the parents. In this
      respect, psychologic support in bridging the gap between cure and care may be
      critical.

PMID- 16567205
TI  - Complications of the tracheal diverticulum after division of congenital
      tracheoesophageal fistula.
AB  - In 3 patients, recurrent respiratory symptoms after neonatal repair of congenital
      tracheoesophageal fistula (Gross type C in 2, D in 1) were associated with a
      large tracheal remnant of the fistula termed diverticulum. Symptoms resolved
      after resection of the diverticulum in 1 child with airway obstruction and 1
      adult with recurrent tracheoesophageal fistula.

PMID- 16567206
TI  - The use of octreotide to treat congenital chylothorax.
AB  - We report the use of the octreotide (a somatostatin analogue) in the treatment of
      idiopathic congenital chylothorax in a patient with Turner's syndrome who had
      previously failed conservative medical therapy. The patient improved rapidly
      after initiation of octreotide with complete resolution after 5 days of
      continuous therapy (10 microg/kg per hour).

PMID- 16567207
TI  - Successful surgical treatment of a 4-month infant after exsanguination for
      aortoesophageal fistula.
AB  - We report on the case of a 4-month infant in hypovolemic shock for severe
      digestive hemorrhage 38 days after surgical treatment of a double aortic arch who
      underwent a successful emergency thoracotomy for suspicion of an aortoesophageal
      fistula.

PMID- 16567208
TI  - Colonic stricture mimicking Hirschsprung's disease: a localized cytomegalovirus
      infection.
AB  - The diagnosis of congenital cytomegalovirus (CMV) infection is best established
      by isolating the virus from urine or saliva within the first 2 weeks of life.
      Detection beyond this point may reflect perinatal acquisition of CMV.
      Cytomegalovirus is usually transmitted by direct human-to-human contact through
      vertical or horizontal routes. Infected persons can excrete CMV in urine, saliva,
      semen, cervical secretions, or breast milk. Because the virus establishes latent
      infections, blood products and solid organs can also transmit CMV. In the
      surgical literature, intestinal CMV-infected cells in infants have prevalently
      been associated with neonatal necrotizing enterocolitis, and only very few cases
      of primary CMV infection of the gastrointestinal tract of surgical interest in
      immunocompetent neonates have been reported. We describe a neonate with
      congenital or perinatal CMV infection with gastrointestinal involvement who
      developed a colonic stricture and manifested a clinical picture simulating
      Hirschsprung's disease. The intestinal lesion was a localized segmental CMV
      infection of the colon in which inflammation dominated the histopathologic
      finding. Chorioretinitis was also present.

PMID- 16567209
TI  - Metastatic rhinosporidioma in a child.
AB  - Rhinosporidiosis is a chronic granulomatous disease caused by Rhinosporidium
      seeberi. It commonly affects nasal mucosa and conjunctiva. Subcutaneous disease
      is unusual and it is often mistaken for soft-tissue sarcoma. Such tumoral
      rhinosporidiosis has never been reported in children. This report describes, for
      the first time, an 11-year-old girl who presented with nasal polyp and multiple
      metastatic swellings of rhinosporidial origin. Fine-needle aspiration cytology
      and histopathology were diagnostic. Surgical excision, followed by dapsone
      therapy, was found to be useful.

PMID- 16567210
TI  - Antral mucosal valve: a rare cause of gastric outlet obstruction in newborn.
AB  - A 15-day male neonate presented with postprandial nonbilious vomiting. Barium
      meal suggested pyloric obstruction. Ultrasound of the stomach after saline
      loading revealed an echogenic antral valve. Subsequent laparotomy confirmed the
      ultrasound findings. Excision of the valve resulted in excellent recovery. To our
      knowledge, gastric outlet obstruction because of an antral mucosal valve in a
      neonate has not previously been described.

PMID- 16567212
TI  - A new simplified technique for needlescopic inguinal herniorrhaphy in children.
AB  - BACKGROUND: Needlescopic techniques have been used recently in repairing inguinal
      hernias (IHs), which made this type of surgery more feasible and less invasive.
      The technique is being developed further. OBJECTIVE: The objective of this study
      was to describe and assess the results that can be achieved by using a new
      simplified technique (Reverdin needle) in needlescopic inguinal herniorrhaphy in
      children. PATIENTS AND METHODS: All patients with symptomatic IH confirmed by
      clinical examination were subjected to elective needlescopic herniorrhaphy. One
      hundred fifty patients with 186 groin hernias, from 2 hospitals in Egypt and
      Saudi Arabia, in the period from October 1999 to May 2002, were assigned to
      needlescopic inguinal herniorrhaphy using Reverdin needle. Reverdin needle was
      used to insert a purse-string suture around the internal inguinal ring to be tied
      extracorporeally. RESULTS: A total of 186 inguinal hernial defects in 150
      children were repaired successfully. There were 130 males and 20 females with a
      mean age of 20.58 +/- 21 months (range, 8-96 months). Right-sided IH was present
      in 86 patients (57.33%); among these patients, an opened internal inguinal ring
      was found and repaired in 12 cases (8%). Left-sided IH was present in 30 (20%),
      bilateral hernia in 19 cases (12.67%), and recurrent IH in 20 cases (10%). The
      mean duration of surgery was 8.7 +/- 1.18 minutes for unilateral and 12.35 +/- 2
      minutes for bilateral hernia repair. There were no intraoperative or
      postoperative complications. The mean hospital stay was 6 +/- 1.21 hours.
      CONCLUSION: The new technique had all the advantages of needlescopic
      herniorrhaphy in children (less invasive, less pain, short hospital stay)
      combined with the advantages of reduced operating time, simplicity, and
      feasibility. It may be preferable to the intracorporeal suturing and knot tying.
      However, it needs long-term follow-up.

PMID- 16567211
TI  - A novel laparoscopic technique for the repair of pediatric umbilical and
      epigastric hernias.
AB  - BACKGROUND/PURPOSE: The aim of this study was to determine whether a novel
      laparoscopic technique for pediatric umibilical and epigastric hernia repair is
      safe, quick, effective, durable, and cosmetically acceptable. METHODS: Forty-one
      consecutive umbilical and 13 epigastric hernias were repaired laparoscopically.
      Six patients had concomitant epigastric and umbilical hernias repaired during one
      procedure. Two 3-mm ports were used via a lateral approach. Mean age was 4.2
      years for those with an umbilical hernia and 2.0 years for those with an
      epigastric hernia. RESULTS: All procedures were completed laparoscopically. The
      mean operative time was 27 minutes for umbilical hernia repair and 16 minutes for
      epigastric hernia repair. There were no intraoperative or postoperative
      complications. Follow-up was 100% and ranged from 6 to 35 months. There have been
      no recurrent hernias, and patient/parent satisfaction was subjectively excellent.
      CONCLUSION: This case series demonstrated that this novel technique of
      laparoscopic anterior abdominal wall hernia repair is safe, quick, effective,
      durable, and cosmetically acceptable. It requires few instruments and minimal
      advanced laparoscopic techniques.

PMID- 16567213
TI  - Multiple mesenteric teratomas: usefulness of spiral computed tomography with 3
      dimensional reconstruction.
AB  - A very rare case of mesenteric teratoma is reported. Complete tumor resection is
      the main prognostic factor for survival in such cases. Therefore, an important
      factor for successful surgery is the exact preoperative visualization of the
      extent of the tumor, including visualization of the abdominal arteries. This
      report describes the use of spiral computed tomography with 3-dimensional
      reconstruction for visualization of the extent of multiple mesenteric teratomas.

PMID- 16567214
TI  - Preoperative magnetic resonance imaging for intralobar pulmonary sequestration.

PMID- 16567215
TI  - The value of open surgical approaches for aspirated pen caps: revisited.

PMID- 16567217
TI  - Possibility that esophageal atresia (EA) carries an increased risk for esophageal
      carcinoma.

PMID- 16567218
TI  - Some more about intrapericardial teratomas in perinatal period.

PMID- 16567222
TI  - The changing indications of gastrointestinal decontamination in poisonings.
AB  - Gastrointestinal (GI) decontamination is commonly used in the treatment of the
      poisoned patient. Although the practice is widely accepted, the science behind
      the recommendations is limited. This article describes commonly used techniques
      for GI decontamination and critically reviews the studies evaluating these
      treatments.

PMID- 16567223
TI  - Utilizing the laboratory in the poisoned patient.
AB  - This article examines the role of common laboratory tests in the evaluation of a
      poisoned patient. Numerous laboratory tests maybe useful to clinicians caring for
      poisoned patients. Clinicians should not order a broad range of tests
      indiscriminately, but rather thoughtfully consider appropriate tests. The results
      of the tests should be reviewed in the context of the clinical scenario.

PMID- 16567224
TI  - Differentiating the causes of metabolic acidosis in the poisoned patient.
AB  - Numerous drugs and toxins may induce the development of a metabolic acidosis. The
      treating physician should be cognizant of the many compounds that can produce
      metabolic acidosis following an overdose or an accidental exposure, or with
      therapeutic use. Knowledge and comprehension of the substances associated with
      metabolic acidosis will facilitate the diagnosis and treatment of poisoned
      patients.

PMID- 16567225
TI  - Acetaminophen poisoning.
AB  - Acetaminophen (acetyl-para-amino-phenol or APAP), an antipyretic and analgesic,
      is a common component in hundreds of over-the-counter and prescription
      medications. The wide usage of this drug results in many potentially toxic
      exposures. It is therefore critical for the clinician to be comfortable with the
      diagnosis and treatment of APAP toxicity. Prompt recognition of APAP overdose and
      institution of appropriate therapy are essential to preventing morbidity and
      mortality.

PMID- 16567227
TI  - Toxicity associated with carbon monoxide.
AB  - Carbon monoxide is an insidious poison that accounts for thousands of deaths each
      year in North America. Clinical effects maybe diverse and include headache,
      dizziness, nausea, vomiting,syn-cope, seizures, coma, dysrhythmias, and cardiac
      ischemia. Children, pregnant women, and patients who have underlying
      cardiovascular disease are particularly at risk for adverse out-comes. Treatment
      consists of oxygen therapy, supportive care, and, in selected cases, hyperbaric
      oxygen therapy.

PMID- 16567226
TI  - Heavy metal poisoning: clinical presentations and pathophysiology.
AB  - Humans have had a long and tumultuous relationship with heavy metals. Their
      ubiquitous nature and our reliance on them for manufacturing have resulted at
      times in exposures sufficient to cause systemic toxicity. Their easy acquisition
      and potent toxicity have also made them popular choices for criminal poisonings.
      This article examines the clinical manifestation and pathophysiology of poisoning
      from lead, mercury, arsenic, and thallium.

PMID- 16567228
TI  - Cocaine-induced chest pain.
AB  - Cocaine-associated chest pain is a clinical entity that crosses all socioeconomic
      groups and hence will be encountered by many physicians. The initial evaluation
      and treatment of cocaine-induced chest pain are similar to those of patients who
      have non-cocaine-induced chest pain, but there are several notable exceptions.
      This article reviews the pathophysiology, evaluation, management, and disposition
      decisions unique to patients presenting with cocaine-induced chest pain.

PMID- 16567229
TI  - New drugs of abuse in North America.
AB  - The term "drugs of abuse" usually brings to mind traditional street drugs, such
      as cocaine, heroin, marijuana, and methamphetamine. The drug scene, however, is
      constantly evolving. As various law enforcement agencies pursue and dismantle
      distribution and pro-duction organizations of the usual drugs of abuse, dealers
      and users are turning to less known, more accessible, and often currently licit
      substances. The widespread growth of the Internet with its vast distribution of
      information has increased the accessibility ofa host of substances and
      facilitated synthesis and production of various substances by individuals. This
      article discusses several new and emerging abused substances, including new
      synthetic variations, plants, and pharmaceuticals diverted for abuse.

PMID- 16567230
TI  - Hyperthermic syndromes induced by toxins.
AB  - Normal thermogenesis requires a complex interaction between systems that generate
      and dissipate heat. Serving as director of thermogenesis, the hypothalamus
      activates the sympathetic nervous system along with the thyroid and adrenal
      glands to respond to changes in body temperature. Working in concert, these
      systems result in heat generation by uncoupling of oxidative phosphorylation,
      combined with impaired heat dissipation through vasoconstriction. In this
      article, the authors discuss serotonin and sympathomimetic syndromes, neuroleptic
      malignant syndrome,and malignant hyperthermia and how these syndromes affect the
      hypothalamic and sympathetic nervous systems, resulting at times in severe
      hyperthermia. Current treatment recommendations and future trends in treatment
      are also discussed.

PMID- 16567231
TI  - Chemically induced seizures.
AB  - Drug- and toxin-associated seizures (DTS) may result from exposure to a wide
      variety of agents. Most DTS can be managed with supportive care. First-line
      anticonvulsant therapy should include benzodiazepines, unless agents require a
      specific antidote. Phenytoin is generally not expected to be useful for DTS and
      in some instances may be harmful. In this article the authors discuss the
      pathophysiology of DTS, the potential differential diagnosis, and the clinical
      presentation. They also review selected agents that cause DTS and provide an
      overview of how the clinician should approach the management of patients who have
      DTS.

PMID- 16567232
TI  - Brown recluse spider envenomation.
AB  - Brown recluse spider bite is a common diagnosis in almost every state in America.
      In fact, cases have been reported in areas where the spider has never been seen.
      A review of medical literature reveals that most current concepts regarding brown
      recluse spider envenomation are based on supposition. In this article, we attempt
      to review critically our present understanding of brown recluse bites with a
      focus on the published evidence.

PMID- 16567233
TI  - Hepatotoxicity associated with herbal products.
AB  - A significant number of herbal products have been associated with hepatotoxicity.
      Attribution of liver injury to a specific herbal pro-duct may be difficult. There
      are few clinical or laboratory manifestations that specifically suggest that
      liver injury is the result of aspecific herbal. Compounding this difficulty is
      that the patient may have liver disease from another cause, may be consuming
      other potentially hepatotoxic products, or may be using a contaminated herbal
      product. The most important clue often is the temporal relationship between
      initiation of the herbal product and the appearance of liver injury; of equal
      importance is the resolution of the injury following withdrawal of the herbal
      product.

PMID- 16567234
TI  - Criminal poisoning: Munchausen by proxy.
AB  - The diagnosis and subsequent prosecution of Munchausen by proxy (MBP) cases
      require the collaborative teamwork of health care teams, laboratory personnel,
      law enforcement, and social services. Poisoning occurs in a significant number of
      the MBP cases with a diverse variety of agents used. To aid laboratory
      professionals in determining the appropriate toxicology tests to perform in such
      criminal cases, health care professionals must focus their testing requests on
      substances that correspond to the victim's signs, symptoms, and ancillary test
      values. This article reviews MBP, with particular focus on poisoning agents that
      have been used in past reported cases.

PMID- 16567235
TI  - Criminal poisoning: medical murderers.
AB  - It is impossible to determine the true incidence of homicides that occur within
      health care facilities. Over the years there have been numerous documented
      examples of health care providers preying on helpless patients. For several
      reasons, the health care system has been inadequate in its response. This article
      reviews some of those cases, the hospitals' responses, and the outcome of
      investigations,to reveal the common factors that can identify the warning signs
      of these tragic events.

PMID- 16567237
TI  - Long-term posttransplantation care: the expanding role of community
      nephrologists.
AB  - Improvements in transplantation practices, immunosuppressive agents, and
      management of comorbid conditions have led to better outcomes for kidney
      transplant recipients. Transplantation has become the treatment of choice for
      patients with end-stage renal disease (ESRD). This has resulted in continued
      growth in the number of patients living with a functioning kidney allograft as a
      percentage of the total ESRD population. These patients require long-term follow
      up care, which already is straining the limited resources of transplant centers.
      Community nephrologists are the logical choice to assume responsibility for the
      posttransplantation care of these patients after discharge from transplant
      centers when they are stabilized. Optimal management of kidney transplant
      recipients depends on regular interactive communication between the patient's
      community nephrologist and the transplant center. Open communication will not
      only facilitate the initial transition of care, it also will decrease the
      frequency of referrals back to the transplant center. In an ideal situation, the
      transplant center and community nephrologist would develop and discuss plans for
      discharge and transition of care for the individual patient before the actual
      kidney transplantation. Important issues for effective communication include
      changes in laboratory results and kidney function; pretransplantation and
      posttransplantation comorbid conditions, surgical complications, or adverse
      effects of medications; modifications to immunosuppressive therapy or other
      medications; recurrent hospitalizations or emergency care; and changes in biopsy
      results.

PMID- 16567238
TI  - Recommendations for outpatient monitoring of kidney transplant recipients.
AB  - Clinical and laboratory outpatient monitoring is an important tool in the
      prevention and management of complications associated with kidney transplantation
      and immunosuppressive therapy. In the absence of standard protocols for
      outpatient surveillance of kidney transplant recipients, recommendations for
      frequency and type of monitoring are determined by the likelihood of problems
      that are unique to the individual transplant recipient and the particular
      posttransplantation period. In addition, it is imperative to maintain the
      transplant recipient's overall health by screening for conditions or diseases
      that can be linked to prior renal disease, immunosuppressive therapies, and
      general health maintenance.

PMID- 16567239
TI  - Current and evolving immunosuppressive regimens in kidney transplantation.
AB  - The advent of novel immunosuppressive agents with increased potency now offers
      multiple treatment options for transplant physicians. However, variable efficacy,
      drug-drug interactions, and adverse effects associated with long-term
      immunosuppression continue to complicate the clinical management of kidney
      transplant recipients. Currently, investigators are challenged to develop
      regimens that take into account not only efficacy, but also dosing, monitoring,
      safety, and patient quality of life. Recent research has focused on evaluating
      new combinations of approved agents that seek to improve outcomes by improving
      control of immunologic events with fewer complications. This article reviews
      current practice and recent studies to give all health care providers who manage
      kidney transplant recipients a better understanding of current regimens and
      general trends in immunosuppressive therapy.

PMID- 16567240
TI  - Maintenance immunosuppression regimens: conversion, minimization, withdrawal, and
      avoidance.
AB  - A wide choice of drug combinations is available to clinicians for
      immunosuppression regimens for their kidney transplant patients. Although many
      protocols have minimized early graft loss, the optimal long-term regimen is
      unknown. Recent studies clearly showed that cardiovascular death is now the
      leading cause of graft loss. Strategies must be developed that address this risk
      while keeping immunologic events low. Transplant physicians have focused on
      exploring regimens that minimize or avoid the use of corticosteroids. Studies
      also have started to explore protocols that minimize calcineurin inhibitor
      therapy.

PMID- 16567241
TI  - Overcoming barriers to long-term graft survival.
AB  - Although short-term kidney graft survival has improved in recent years, the focus
      has shifted to the challenge of improving long-term graft survival. Acute
      rejection, chronic allograft nephropathy, and cardiovascular disease are
      associated with graft loss and patient death. Reducing the potential for such
      posttransplantation complications may improve long-term graft survival. In
      addition, gaining a better understanding of the role that various
      immunosuppressive therapies have in decreasing the risk for graft injury will
      help clinicians make better-informed decisions about appropriate treatment
      regimens for individual kidney transplant recipients.

PMID- 16567242
TI  - Long-term patient survival: strategies to improve overall health.
AB  - The use of potent immunosuppressant therapy has led to an increase in number of
      patients with successful long-term kidney transplants. These individuals come to
      kidney transplantation with varying levels of comorbidity associated with end
      stage renal disease and are susceptible to immunologic and nonimmunologic
      comorbidities that arise late after transplantation, including cardiovascular
      disease, infection, malignancy, and bone disease, which negatively impact on
      patient and graft survival. In addition, nonadherence to immunosuppressant
      regimens increases with time after transplantation, which further augments the
      risk for late-term graft failure and mortality. Consistent and frequent follow-up
      of kidney transplant recipients beyond the first year permits early diagnosis and
      successful treatment of many posttransplantation comorbidities. Implementation of
      preventive practices and aggressive management of risk factors throughout the
      life of the transplant improves overall health and long-term outcomes.
      Establishment and maintenance of close relationships among transplant centers,
      physicians, patients, and their families improves patient adherence to
      medications and reduces the risk for morbidity and mortality.

PMID- 16567243
TI  - Challenges in the counseling and management of older kidney transplant
      candidates.
AB  - Patients aged 60 years and older represent the fastest-growing population with
      chronic kidney disease and end-stage renal disease (ESRD). In 2002, a total of
      137,000 patients aged 65 years and older were on dialysis therapy in the United
      States, but only a highly selected minority of them (5%) were on the waiting list
      for a kidney transplant. The majority of older patients on dialysis therapy are
      not being referred for the waiting list, presumably because of comorbid diseases
      and lower life expectancy. However, kidney transplantation clearly has been shown
      to improve survival compared with dialysis, even for older patients. Because both
      patient age and time on the transplant waiting list increase the risk for death,
      older patients (ie, > or =60 years) who already have a shorter life expectancy
      than younger patients are more likely to die with a functioning graft. The
      limited supply of deceased-donor kidneys and increasing number of patients who
      would benefit from transplantation have created a dilemma about how to fairly
      allocate donor kidneys among patients of all ages while meeting the needs of the
      increasing number of older patients with ESRD. Although older dialysis patients
      receive fewer kidney transplants than younger patients, their patient and graft
      survival rates are good. Instead of applying rigid age limits, the "biological,"
      rather than "chronological," age of individual patients should be assessed
      carefully to help clinicians select the most appropriate candidates for kidney
      transplantation and reduce morbidity and mortality in older transplant
      recipients.

PMID- 16567244
TI  - Posttransplantation quality of life: more than graft function.
AB  - Whereas newer immunosuppressive therapies have increased patient and graft
      survival, long-term treatment with these drugs has been linked to medical and
      physical complications that may impact on posttransplantation quality of life.
      Immunosuppression-related physical side effects that can alter appearance-
      including hirsutism, gingival hyperplasia, weight gain, cushingoid facies, hand
      tremors, alopecia, and skin disorders--are among the most bothersome to patients
      and may have serious psychosocial implications. In addition, physical side
      effects may influence patient adherence to their prescribed treatment regimens
      and result in more serious complications, such as acute rejection, graft loss,
      rehospitalization, and even mortality. Therefore, strategies for minimizing side
      effects of immunosuppressive therapy and improving medication adherence are
      integral to better long-term transplant recipient management.

PMID- 16567245
TI  - The ability of paramedics to predict aspiration in patients undergoing
      prehospital rapid sequence intubation.
AB  - One of the purported benefits to invasive prehospital airway management is the
      prevention of aspiration; however, aspiration events may occur before the arrival
      of prehospital personnel. We explore the timing of aspiration in patients with
      severe traumatic brain injury (TBI) undergoing paramedic rapid sequence
      intubation (RSI). Severely head-injured (Glasgow Coma Scale [GCS] score 3-8)
      adults were prospectively enrolled into the San Diego Paramedic RSI Trial. As
      part of the prehospital data collection tool, paramedics prospectively assessed
      for clinical evidence of aspiration before RSI (pre-intubation), aspiration
      events occurring during RSI (peri-RSI), and regurgitation of vomitus or blood
      after intubation (post-intubation). Data were abstracted from work sheets used
      during the RSI procedure, a telephone debriefing by one of the principal
      investigators immediately after delivery of the patient, and San Diego County
      prehospital and trauma databases. The incidence of pre-intubation aspiration,
      peri-RSI aspiration, and post-intubation regurgitation of vomitus or blood were
      determined. Patients with and without pre-intubation aspiration were compared
      with regard to pre- and post-intubation hypoxia and the rate of aspiration
      pneumonia. Logistic regression was used to explore the association between pre
      intubation aspiration and various demographic and clinical factors. The results
      showed that pre-intubation aspiration was noted by paramedics in 72/269 patients
      in whom complete data were available. Peri-RSI aspiration was reported in one
      patient; there were no reported cases of post-intubation regurgitation of vomitus
      or blood. Patients in the pre-intubation aspiration group required more
      intubation attempts, had a higher incidence of desaturations and lower pre- and
      post-intubation SaO(2) values, and were more frequently diagnosed with aspiration
      pneumonia. Pre-intubation aspiration was associated with severe TBI, GCS score of
      3, younger age, and the absence of alcohol intoxication despite controlling for
      age, gender, GCS, Head AIS (Abbreviated Injury Score), and serum ethanol. It is
      concluded that paramedics seem to be able to accurately assess for aspiration in
      patients undergoing prehospital RSI. The vast majority of aspiration events seem
      to occur before the arrival of prehospital personnel. Alteration in consciousness
      from TBI may carry a higher risk of aspiration than with other causes, such as
      alcohol intoxication.

PMID- 16567247
TI  - Traumatic, pericardio-diaphragmatic rupture: an extremely rare cause of
      pericarditis.
AB  - A 54-year-old man with a recent history of blunt abdominal trauma presented to
      the Emergency Department with severe pain in the chest and abdomen. He was
      tachycardic, tacypneic, and hypoxic. An electrocardiogram (EKG) at that time
      showed ST elevation and PR depression consistent with acute pericarditis, and a
      computed tomography (CT) scan subsequently showed herniation of abdominal
      contents into the pericardium and left hemithorax. After surgical repair of the
      diaphragmatic defect and intrapericardial hernia, the EKG findings resolved. He
      recovered over the course of several weeks and was subsequently discharged home.

PMID- 16567246
TI  - Isolated obturator externus muscle abscess presenting as hip pain.
AB  - The case of a 20-year-old diabetic male with 2 weeks of hip pain, diagnosed with
      an isolated obturator externus muscle abscess, is reported. Pyomyositis, or
      abscess formation deep within a large striated muscle, is a rare but potentially
      life-threatening disease.

PMID- 16567248
TI  - Pneumobilia: benign or life-threatening.
AB  - Pneumobilia, or air within the biliary tree of the liver, suggests an abnormal
      communication between the biliary tract and the intestines, or infection by gas
      forming bacteria. Pneumobilia usually can be distinguished from air in the portal
      venous system by its appearance on computed tomography (CT) scan. The most common
      conditions associated with pneumobilia include: 1) a biliary-enteric surgical
      anastamosis, 2) an incompetent sphincter of Oddi, or 3) a spontaneous biliary
      enteric fistula. Three cases of pneumobilia associated with its most common
      causes are presented and further differential diagnostic possibilities as well as
      the implications of this finding on patient management are discussed.

PMID- 16567249
TI  - Spontaneous rupture of an umbilical hernia with evisceration.
AB  - Umbilical hernias are a common complication of persistent ascites. Spontaneous
      rupture of these hernias is a less common complication. We report a case of
      spontaneous evisceration through an umbilical hernia in a cirrhotic patient with
      chronic ascites. Definitive surgical repair of the evisceration was not possible
      secondary to persistent ascites that was refractory to paracentesis and diuresis.
      Transjugular intrahepatic portocaval shunt (TIPS) placement was ultimately
      performed in an attempt to eliminate the ascites fluid. This case demonstrates a
      rare, but life-threatening complication of abdominal ascites that may be
      prevented by aggressive medical and surgical management.

PMID- 16567250
TI  - Wide-complex tachycardia as the presenting complaint in a case of malingering.
AB  - Fabrications of lethal dysrhythmias are an extremely rare manifestation of
      malingering, with only one case described more than two decades ago. Recognition
      of this clinical entity is important because the diagnosis may be difficult to
      make, therapeutic implications for the patient are significant, and financial
      consequences of misdiagnosis are considerable. In this case report, we present an
      unusual example of malingering, in which a patient intentionally mimicked
      repeated episodes of unstable wide-complex ventricular tachycardia, by tapping on
      the chest wall cardiac leads, while feigning concurrent episodes of chest pain.

PMID- 16567251
TI  - Ketamine to avoid mechanical ventilation in severe pediatric asthma.
AB  - Children experiencing severe asthma exacerbations may deteriorate to respiratory
      failure requiring endotracheal intubation and mechanical ventilation. Mechanical
      ventilation is often life saving in this setting, but also exposes the asthmatic
      child to substantial iatrogenic risk. We present two cases of severe asthma
      exacerbations in prepubertal children for whom the administration of a bolus of
      intravenous ketamine followed by a continuous infusion of a relatively large dose
      of ketamine led to prompt improvement, obviating the need for mechanical
      ventilation. These cases suggest that for children experiencing severe asthma
      exacerbations, intravenous ketamine may be an effective temporizing measure to
      avoid exposing these children to the risks associated with mechanical
      ventilation.

PMID- 16567252
TI  - Pit viper envenomation in pregnancy: a case report and literature review.
AB  - Pit viper bites are very rare in pregnant patients and there is no consensus for
      treatment. This case report describes the treatment of a 28-year-old woman at 26
      weeks gestation who suffered a pit viper envenomation.

PMID- 16567253
TI  - Missed abdominal ectopic pregnancy.
AB  - A case of a ruptured 10-week abdominal ectopic pregnancy, originally diagnosed
      and treated as pelvic inflammatory disease, is reported. The patient was treated
      surgically and recovered uneventfully. The case is discussed and a review of the
      literature is presented.

PMID- 16567254
TI  - An unusual case of 4-aminopyridine toxicity.
AB  - 4-aminopyridine (4-AP) is an orphan drug in the United States. It enhances
      neuronal conduction at synapses and is indicated in the treatment of selected
      neuromuscular disorders, including multiple sclerosis and myasthenia gravis,
      among others. Its documented toxicity generally has been limited to central
      nervous system (CNS) hyperexcitation and gastrointestinal upset. In this case, a
      56-year-old man accidentally overdosed on an unknown amount of generic 4-AP. This
      history was unknown by his family and unavailable to initial providers.
      Approximately 1 h after ingestion, his son found him diaphoretic, vomiting, and
      having unintelligible speech. In the ensuing 2-3 h, the patient became moderately
      hypothermic (32.8 degrees C; 91 degrees F), developed atrial fibrillation with a
      rapid ventricular response, and had neurological changes that were confused with
      an acute cerebrovascular accident. After a 36-h stay in the intensive care unit
      that included mechanical ventilation, cardioversion, passive rewarming, and an
      extensive medical workup, the patient recovered without sequelae. After
      extubation he stated that he thought he may have ingested too much 4-AP after
      rubbing a large amount of it against a sore tooth to take advantage of its local
      analgesic properties. This case of 4-AP overdose resulting in atrial fibrillation
      with rapid ventricular response, hypothermia, and acute neurological changes
      mistaken for an acute cerebrovascular accident is an unusual one. This case shows
      that overdose of 4-AP can cause or mimic several serious medical conditions, and
      that a detailed history and physical examination are essential for uncovering
      unusual diagnoses.

PMID- 16567255
TI  - Electrocardiographic changes with segmental akinesia after chloral hydrate
      overdose.
AB  - We report a case of deliberate ingestion of 12.5 g chloral hydrate in a 25-year
      old psychiatric patient. Coma and life-threatening ventricular dysrhythmias were
      observed soon after ingestion. Repeated electrocardiographic examination was
      consistent with ischemic changes appearing on day 3. They were associated with
      segmental abnormal left ventricular wall motion by echocardiography. A coronary
      angiogram was performed and was normal. Toxic metabolites of chloral hydrate,
      trichloroethanol and trichloroacetic acid were found in the urine until day 7.
      This case illustrates that with halogenated aliphatic hydrocarbons, sustained
      changes in cardiac contractility may occur in addition to early life-threatening
      ventricular dysrhythmias.

PMID- 16567257
TI  - Utility of supine oblique radiographs in detecting cervical spine injury.
AB  - A retrospective case-control study was performed to determine if the addition of
      supine oblique radiographs to the routine cervical spine series results in the
      detection of patients with cervical spine injuries not identified with standard
      views alone. The cervical spine radiographs of 82 patients with known cervical
      spine injuries and 180 hospitalized patients without cervical spine injuries were
      collected. Radiographs of the two patient groups were randomly combined to form
      the study sample. The radiographs were reviewed independently by a board
      certified radiologist and a board-certified emergency physician. During the first
      phase, each reviewer was provided with standard views of the cervical spine
      (lateral, anterior-posterior, open-mouth odontoid, and submental views). During
      the second phase, each reviewer was provided with the standard views and supine
      obliques. The reviewers were masked to all clinical information and previous
      radiologic interpretations. The results showed that in the first phase (standard
      views only), the two physicians had a sensitivity of 81% (95% confidence interval
      [CI] 74-87%) and a specificity of 93% (95% CI 90-96%). In the second phase
      (obliques included), the two physicians had a sensitivity of 76% (95% CI 69-83)
      and specificity of 90% (95% CI 87-93%). In a subset analysis of patients with
      posterior element (lamina, facet, and pedicle) fractures, the two physicians had
      a sensitivity of 88% (95% CI 78-95%) with standard radiographs and 86% (95% CI 76
      94%) with the addition of oblique radiographs. In conclusion the addition of
      supine oblique radiographs to the standard trauma cervical spine series did not
      increase the readers' sensitivity for detecting patients with cervical spine
      injuries. Routinely including oblique radiographs in patients undergoing
      radiographic screening of the cervical spine is not warranted.

PMID- 16567256
TI  - Analysis of patients treated during four Disaster Medical Assistance Team
      deployments.
AB  - To aid disaster planning, a retrospective review of patients seen by New Mexico 1
      Disaster Medical Assistance Team (NM-1 DMAT) after four disasters was conducted.
      Data analyzed included age, gender, past medical history, chief complaint,
      diagnosis, diagnostic testing, treatment, triage category, disposition, and time
      to presentation after the disaster. Data were analyzed for differences between
      patients presenting early vs. late after a disaster and to test if availability
      of diagnostic testing changed patient disposition. The results showed that the
      majority of patients presented with upper respiratory tract infection symptoms,
      wounds, and musculoskeletal pain. The needs of patients were similar whether they
      presented early or late. The same proportion of patients was transferred to
      hospitals when diagnostic testing was available vs. not available, despite a
      higher level of acuity when diagnostic testing was available. In conclusion,
      DMATs should be prepared to see high volumes of low acuity patients. Patient
      needs do not change with time. Diagnostic testing may be useful.

PMID- 16567258
TI  - The epidemiology of illness and injury at the alpine venues during the Salt Lake
      City 2002 Winter Olympic Games.
AB  - The Emergency Medicine literature has described levels of medical care for mass
      gatherings in the United States, including for the Los Angeles 1984 Summer and
      Calgary 1988 Winter Olympic Games. However, there are limited data to describe
      the type and number of illness or injury that may occur during mass gatherings in
      an alpine winter environment. To describe the epidemiology of illness and injury
      seen among spectators at the alpine and snowboarding venues during the Salt Lake
      City 2002 Winter Olympic Games, we conducted a retrospective review of the Salt
      Lake City 2002 Olympic Medical Care database for all patient encounters during
      the operational period of the Games at the alpine and snowboarding venues. The
      three venues included were: Deer Valley Resort (DVR), Park City Mountain Resort
      (PCM), and Snowbasin Resort (SBA). Each venue had a medical clinic located on
      site for spectators and another for athletes. Physicians, nurses, emergency
      medical technicians, and therapists staffed the clinics. The database was created
      by Inter-mountain Health Care (IHC) in conjunction with Salt Lake City 2002
      Winter Olympic staff and consisted of descriptive reports of all patient
      encounters from all venues including demographic, epidemiology, and outcome
      information. IHC maintains the database, and was the sole medical provider for
      the Games. Each venue had at least 6 days of competition events. Over the 19 days
      of the Olympiad, a total of 410,160 spectators and 3,961 competitive athletes
      attended the three venues. There were 841 spectators evaluated and treated at the
      venue clinics, and mobile medical staff treated 262 spectators. The top five
      spectator clinic diagnostic categories were: sprain/strain (n=108), miscellaneous
      trauma (n=103), respiratory (n=88), miscellaneous medical (n=69), and digestive
      (n=52). Fifty spectators required transport to a hospital for additional care: 27
      required transfer by ground ambulance and the remainder were transported by
      private vehicle. The overall spectator medical utilization rate was 26.9. In
      conclusion, the rate and acuity of patients seen at the alpine venues during the
      2002 Winter Olympic Games was low. Nevertheless, we recommend full on-site
      physician and nurse staffing with advanced trauma and cardiac life support
      available during similar events.

PMID- 16567259
TI  - Nordic venue medical services during the 2002 Winter Olympics.
AB  - This article represents a retrospective analysis of medical care provided to
      spectators, athletes, officials, and workforce at the cross country skiing and
      biathlon venue, Soldier Hollow, during the 2002 Winter Olympic Games. A
      retrospective chart review was performed of the primary diagnosis category
      assigned to each patient on medical encounter forms completed at the time medical
      care was provided in the athlete or spectator medical clinics. Descriptive
      statistics were used to characterize data from the primary diagnosis categories
      for groups of patients. There were 590 total medical encounters among athlete and
      spectator medical services over 19 operational days with 227,847 total visitors
      (includes spectators, athletes, and workforce). The incidence of medical
      encounters was 26 per 10,000 visitors. There were 215 medical encounters that
      were evaluated and treated by a physician in the athlete (69 cases) or spectator
      (146 cases) medical clinics. The most common diagnoses were related to
      respiratory infection or respiratory disease. There were 177 patients discharged
      without follow-up and 26 referred to a medical facility off venue. Six patients
      were transported to a hospital by ground ambulance. In conclusion, the injuries
      and illnesses evaluated and treated were consistent with prior studies on medical
      care at Olympic Games. Although some patients required ground ambulance transport
      off venue due to injury or illness, there were no critical injuries or illnesses
      that resulted in death. The level of services available to both athletes and
      spectators was more than adequate for the injuries and illnesses encountered.

PMID- 16567260
TI  - Ultrasonographic investigation of the effect of reverse Trendelenburg on the
      cross-sectional area of the femoral vein.
AB  - Emergency physicians often obtain central venous access via the femoral vein in
      critically ill patients or patients with difficult peripheral access due to
      chronic intravenous drug use. Previous studies using two-dimensional
      ultrasonography have demonstrated that the Trendelenburg position increases the
      cross-sectional area of the internal jugular vein. This study is designed to
      determine the effect of the Reverse Trendelenburg position on femoral vein
      dimensions using bedside ED ultrasonography. A prospective, non-randomized
      observational study was conducted that enrolled subjects at an urban Level I
      Trauma Center and an affiliated School of Medicine over a 2-month period.
      Informed consent was obtained from 52 adult subjects with no history of deep
      venous thrombosis or vascular surgery in the lower limbs. Using two-dimensional
      ultrasound with a 7.5-MHz linear transducer, femoral vein cross-sectional areas
      on the right and left sides were measured with subjects supine, and in
      approximately 15 degrees reverse Trendelenburg. The data was analyzed using a two
      tailed Student's t test. The mean cross-sectional area of the femoral vein with
      subjects supine was 0.85 cm(2) (SD +/- 0.41 cm(2)), and 1.22 cm(2) (SD +/- 0.51
      cm(2)) with subjects in reverse Trendelenberg. The cross-sectional area of the
      femoral vein increased significantly (p < 0.001) with the reverse Trendelenburg
      position [55.2% +/- 9.1% (95% CI)]. In conclusion, a significant increase in
      femoral vein cross-sectional area can be achieved with the reverse Trendelenburg
      position. This maneuver may increase the rate of successful femoral vein
      catheterization.

PMID- 16567261
TI  - Heart block and rash.

PMID- 16567262
TI  - Association of Henoch-Schonlein purpura and hepatitis A.

PMID- 16567263
TI  - Thrombolytic treatment of acute pulmonary embolism in myotonic dystrophy.

PMID- 16567264
TI  - Resuscitation attempts in asystolic patients: the legal tail wagging the dog?
AB  - In today's litigious society, legal worries can cause Emergency practitioners to
      alter their delivery of clinical care. One clinical scenario in which this
      particularly true is in resuscitation of the so called "medically futile"
      patient. Patients who arrive to the Emergency Department in prolonged asystole
      have a uniformly dismal prognosis at best. Yet, many Emergency Physicians often
      continue resuscitative efforts for fear of being sued. These fears are largely
      unjustified. This article attempts to analyze the factors and elements involved
      in support of the assertion that the risk of a lawsuit is negligible at best.

PMID- 16567265
TI  - New therapies for uremic secondary hyperparathyroidism.
AB  - Secondary hyperparathyroidism (SHPT) is a common and serious complication of
      chronic kidney disease (CKD). It affects more than 300,000 end-stage renal
      disease patients treated by dialysis and probably more than 3 million patients
      with CKD worldwide. For a long time, traditional therapies for SHPT had consisted
      of correcting the hypocalcemia using calcium salts and vitamin D derivatives,
      preventing the hyperphosphatemia by calcium- or aluminum-containing intestinal
      phosphate binders, and recently by using no metal-containing intestinal phosphate
      binders; however, these therapies are limited by the occurrence of hypercalcemia,
      hyperphosphatemia, and the lack of specificity and long-term efficacy. Moreover,
      surgical parathyroidectomy (PTX), which remains the gold standard therapy, is not
      exempt from risk. PTX exposes patients to anesthesia risks, presurgical and
      postsurgical complications, and in many cases a permanent state of
      hypoparathyroidism. Thus, the medical treatment of SHPT became an ideal target
      for the development of new therapies and strategies. The purpose of this article
      is to provide an overview of these new therapies, including vitamin D analogs,
      intestinal phosphate binders, calcimimetics, parathyroidectomies, tyrosine kinase
      inhibitors, azydothymidine, anticalcineurins, N-terminal truncated parathyroid
      hormone fragments, bisphosphonates, calcitonin, osteoprotegerin, and others. The
      use of these new therapies alone or in combination may help to optimize the
      future treatment of SHPT in CKD patients.

PMID- 16567266
TI  - Disordered mineral metabolism and vascular calcification in nondialyzed chronic
      kidney disease patients.
AB  - It is well established that abnormalities in mineral metabolism are apparent
      early in the course of chronic kidney disease (CKD) and result in clinically
      relevant consequences such as renal osteodystrophy. Furthermore, there is
      emerging evidence linking some of these abnormalities (hyperphosphatemia) to the
      high cardiovascular morbidity and mortality experienced by nondialyzed patients
      with CKD. Most studies have evaluated vascular calcification in patients with
      stage 5 CKD. Reports published over the last 2 years show that the process begins
      rather early in CKD and is particularly severe among elderly and type 2 diabetic
      patients. Furthermore, "calcium begets calcium", such that the calcification
      burden in early CKD is an important predictor of subsequent progression,
      including the rapid increase seen in stage 5 CKD. There is an increasing body of
      evidence that supports the thesis that elevated serum levels of phosphorus and
      calcium and deficiency of inhibitors of calcification (for example, fetuin-A) are
      important in the progression of vascular calcification in patients with end-stage
      renal disease. However, the concentrations of calcium and phosphorus shown to
      induce mineralization in cell culture studies are not observed in most patients
      until late in stage 4 or stage 5 CKD. Cross-sectional and longitudinal studies
      have also been unable to show a correlation between serum levels of markers of
      disordered mineral metabolism and severity of vascular calcification. Future
      studies should evaluate the pathogenetic role of phosphorus retention, which
      occurs early in the course of CKD, in the induction and/or progression of
      vascular calcification. Finally, there is a need to identify alternative
      pathogenetic mechanisms that may be important causes of the high calcification
      burden observed early in CKD.

PMID- 16567267
TI  - Effect of high-dose thiamine and pyridoxine on advanced glycation end products
      and other oxidative stress markers in hemodialysis patients: a randomized placebo
      controlled study.
AB  - OBJECTIVE: To study the effect of high doses of thiamine (250 mg/day) and
      pyridoxine (200 mg/day) supplementation on plasma levels of advanced glycation
      end products and other oxidative stress markers in hemodialysis patients. DESIGN:
      An interventional survey. SETTING: This study was conducted at an outpatient
      nephrology clinic. INTERVENTION AND PATIENTS: We performed a randomized placebo
      controlled study over 8 weeks in 50 patients (53% men, age 52.9 +/- 3.4 years) on
      regular hemodialysis. MAIN OUTCOME MEASURES: The patients were divided into 2
      groups of 25 patients in each arm. Before starting the study, the patients in
      both groups were matched by age, gender, inflammatory profile (plasma interleukin
      [IL]-6 and high-sensitivity C-reactive protein [hsCRP]), and nutritional status
      (subjective global assessment and protein nitrogen appearance). RESULTS: In all,
      40 of 50 patients completed the study (19 patients in the vitamin group and 21 in
      the placebo group). Serum albumin, plasma hsCRP, IL-6, advanced oxidation protein
      products, pentosidine and 8-hydroxy-2'-deoxyguanosine were measured before and
      after treatment in each group. In both groups, over 8 weeks of follow-up, no
      significant differences could be observed in oxidative stress, inflammatory, or
      nutritional markers. CONCLUSIONS: There was no evidence showing that high doses
      of thiamine and pyridoxine affects oxidative stress in hemodialysis patients.

PMID- 16567268
TI  - Relationship between serum carnitine, acylcarnitines, and renal function in
      patients with chronic renal disease.
AB  - BACKGROUND: Serum free carnitine is decreased and serum acylcarnitines are
      increased in maintenance hemodialysis (MHD) patients, and the causes for these
      abnormalities are not known. This study examined the role of renal failure in the
      occurrence of low serum carnitine and increased acylcarnitines in patients with
      advanced chronic kidney disease (CKD) by assessing the relationship between these
      compounds and renal function in normal individuals and patients with CKD. If
      these compounds decrease as glomerular filtration rate (GFR) decreases, this
      suggests that decreased intake or impaired synthesis in kidneys explain the low
      serum values. If serum compounds increase as GFR decreases, this suggests that
      impaired excretion may predispose to these values. METHODS: The study, conducted
      in Lyon, France (part A), and Los Angeles, California (part B), compared serum
      free carnitine and acylcarnitines to renal function in 20 normal patients, 65 CKD
      patients, and 29 MHD patients. GFR was measured using inulin (A) and iothalamate
      (B) clearances. Carnitine compounds were measured by tandem mass spectrometry (A)
      and electron spray mass spectrometry (B). RESULTS: There was no relationship
      between serum total carnitine or free carnitine and GFR in the normal subjects
      and CKD patients. In contrast, serum acylcarnitines were inversely correlated
      with GFR in these 2 groups. Serum free carnitine was significantly lower in MHD
      patients than in CKD patients and normal controls in study B, whereas
      acylcarnitines were significantly greater than controls in studies A and B and
      than in CKD patients in study A. CONCLUSIONS: Serum free carnitine is not reduced
      in CKD and decreases in MHD patients. Serum acylcarnitines increase in CKD and
      MHD patients primarily because of impaired excretory function in the failing
      kidney.

PMID- 16567269
TI  - Menu suggestion: an effective way to improve dietary compliance in peritoneal
      dialysis patients.
AB  - OBJECTIVE: Poor compliance with the dietary prescriptions is quite common in
      dialysis patients. We believe that most of the noncompliance is caused by the
      patient's poor understanding of the dietary prescription. Therefore, in the
      present study, we tried to investigate the role of menu suggestion in improving
      the patient's compliance with the dietary prescription. DESIGN AND SETTING: A
      longitudinal cohort study conducted at an outpatient dialysis clinic. PATIENTS:
      Seventy clinically stable patients on peritoneal dialysis were included in this
      prospective study during April 1, 2004, to November 31, 2004, in a single center.
      Patients who had significant cognitive impairment and thus did not understand the
      food contents during the training course were not eligible for enrollment.
      INTERVENTION: All the patients were randomly assigned to 1 of 2 groups. Group 1
      patients received the traditional patient education method. Group 2 patients
      additionally received individualized menu suggestions based on their food
      preferences and education on how to exchange the foods at equivalent amounts
      according to the exchange list. MAIN OUTCOME MEASURES: At present, there are no
      clear optimal dietary protein intake levels for peritoneal dialysis patients. Our
      experience is that a dietary protein intake level of 0.8 to 1.2 g/kg/d can
      maintain our patients in a good nutritional status. Thereafter, in this study we
      prescribed the dietary protein intake level at 0.8 to 1.2 g/kg/d and defined
      compliance as meeting this target protein intake level. RESULTS: There were 35
      patients in each group. The compliance was 22.9% in group 1 and 57.1% in group 2
      (P < .05). CONCLUSIONS: Our study suggests that menu suggestion may be an
      effective way of improving the compliance with the diet in peritoneal dialysis
      patients. It improves the patient's understanding of the dietary prescription.

PMID- 16567270
TI  - Bioelectrical impedance analysis before versus after a hemodialysis session in
      evaluation of nutritional status.
AB  - OBJECTIVE: The objective of our study was to evaluate whether bioelectrical
      impedance analysis (BIA) performed 15 minutes after a hemodialysis (HD) session
      is clinically useful in nutrition status assessment in comparison with BIA
      performed before HD. Because of better reliability, it is postulated in the
      literature that BIA measurements should be performed 1 to 5 hours after HD
      sessions. However, the measurements 1 to 5 hours after HD sessions are
      inconvenient in clinical practice. Furthermore, the currently published BIA
      reference values for the HD population are based on the measurements taken before
      HD sessions. METHODS: The study group consisted of 29 HD patients who were in a
      stable clinical condition. BIA measurements were performed by means of BIA 101
      System (Akern RJL Systems, Florence, Italy). The correlation coefficients were
      surveyed between traditional indices of nutritional status, such as body mass
      index (BMI) and plasma concentrations of protein, albumin, and nonprotein
      nitrogen blood urea nitrogen (BUN) (measured before HD) on one hand, and BIA
      parameters (taken before and 15 minutes after HD) on the other hand. RESULTS:
      Statistically significant correlations occurred between such BIA parameters as
      (1) phase angle and BMI or albumin, or total protein or BUN and (2) body cell
      mass and BMI or BUN. The differences between correlation coefficients achieved
      either before or after HD were statistically nonsignificant. CONCLUSIONS: BIA
      measurements in the studied group of patients did correlate with traditional
      indices of nutritional status. The correlation coefficients were not
      significantly influenced by the time of performing BIA measurements. The obtained
      correlations confirm that BIA performed 15 minutes after an HD session may be a
      useful tool in evaluation of nutritional status of stable HD patients in clinical
      practice.

PMID- 16567271
TI  - Circulating growth hormone binding protein levels and mononuclear cell growth
      hormone receptor expression in uremia.
AB  - BACKGROUND: Resistance to growth hormone (GH) in end-stage renal disease (ESRD)
      causes growth retardation and muscle wasting. In humans, circulating GH binding
      protein (GHBP), the extracellular domain of the GH receptor that is shed into the
      circulation and is believed to reflect tissue GH receptor levels, is reduced in
      uremia and suggests that cellular GH receptor levels are correspondingly reduced.
      If true, this could be a cause of GH resistance. We set out to establish whether
      serum GHBP levels reflect cellular GH receptor levels and whether changes in
      serum GHBP levels are related to nutritional or inflammatory status. METHODS: GH
      receptor protein expression in peripheral blood mononuclear cells (PBMC) from 21
      ESRD and 14 normal subjects were analyzed by fluorochrome flow cytometry.
      RESULTS: The GH receptor density and percent total PBMCs expressing the GH
      receptor were similar in the 2 groups, and there was no difference in percent GH
      receptor positive T or B cells or monocytes. In contrast, serum GHBP levels were
      80% lower in ESRD. GHBP levels did not correlate with serum albumin, body mass
      index, or muscle mass but seemed to be partly related to the log serum C-reactive
      protein levels. CONCLUSIONS: Serum GHBP levels are markedly reduced in ESRD; this
      seems to occur independent of nutritional status and may in part be caused by
      inflammation. Because GH receptor expression on PBMC of ESRD and control subjects
      was similar, our findings argue against a reduction in GH receptor as a cause of
      GH resistance and the use of serum GHBP levels as a reliable marker of specific
      tissue GH receptor levels.

PMID- 16567272
TI  - The use of neural networks in evaluation of the direction and dynamics of changes
      in lipid parameters in kidney transplant patients on the Mediterranean diet.
AB  - OBJECTIVE: The objective of the study was to assess whether neural networks can
      be a tool useful in the evaluation of the effect of the Mediterranean diet (MD)
      on the direction and dynamics of selected parameters. DESIGN: Randomized,
      prospective study. SETTING: Outpatient Clinic of the Department of Nephrology,
      Transplantology, and Internal Medicine. PATIENTS AND INTERVENTION: The study
      group consisted of 21 patients after kidney transplantation whose diet complied
      with the MD; the control group included 16 patients (also after transplantation)
      on a low-fat diet, isocaloric with the study diet. MAIN OUTCOME MEASURES:
      Anthropometry, plasma lipids, chromatography of triacylglycerols and fatty acids,
      and activity of superoxide dismutase and catalase were measured in both groups.
      Statistical analysis was done with the SNN (Statistica Neural Networks) StatSoft
      software package. RESULTS: The advantage of neural networks is the possibility of
      the dynamic presentation of a process taking place in a biological system. In the
      MD group in the first months of use of the diet, the cholesterol level was
      reduced only in the group of young and middle-aged patients. This tendency was
      not observed among elderly patients, among whom a small reduction of the total
      cholesterol level was noted only at the end of the observation period. In control
      group at the beginning of the observation, the plasma total cholesterol level was
      proportional to the patient's age. After 6 months, the total cholesterol
      increased in young patients and redacted in the group of elderly patients.
      CONCLUSIONS: We concluded that the MD diet would be ideal for posttransplantation
      patients without serious pathologic dyslipidemia. In the case of patients with
      substantial dyslipidemia, appropriate pharmacologic treatment lowering
      proatherosclerotic lipid levels should be used in combination with the MD.
      Artificial neural networks (ANNs) were a useful tool in modeling biological
      parameters, showing dynamics of the studied interactions in a very detailed way.
      ANN is the most suitable method for investigations with many variables,
      interconnected nonlinearly; therefore, this method allows for a more general
      approach to biological problems. However, it should be noted that considerable
      data sets are required to obtain a satisfactory fit to the data. Moreover, to
      ensure the predictive power of this method for new cases, the representative
      database is indispensable. In spite of these demands, ANN is a prospective tool
      for reliable, quick assessments and predictions.

PMID- 16567273
TI  - Scope of practice in renal nutrition.
AB  - Clinical standards for practice in renal nutrition can vary dramatically from
      region to region, state to state, and clinic to clinic, and are greatly affected
      by the policies of several governing bodies. This review explores the factors
      that influence practice patterns among renal dietitians and examines the current
      American Dietetic Association's Scope of Dietetics Practice Framework for its
      applicability to kidney disease. Lastly, this article discusses current
      strategies for establishing a scope of practice in renal nutrition and evaluates
      licensure and credentialing issues that impact standards for practice across the
      various regions of the United States.

PMID- 16567274
TI  - Desserts first.

PMID- 16567275
TI  - Food fortification and nutrition labeling: implications for patients with kidney
      disease.

PMID- 16567276
TI  - "Live now, pay later".

PMID- 16567277
TI  - Adult-onset foveomacular vitelliform dystrophy.
AB  - BACKGROUND: Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a condition
      that presents classically as bilateral, symmetrical, grayish-yellow, round or
      oval-shaped lesions within the macular area. These lesions are mildly elevated
      and are typically one third to one half disc diameter in size. The onset of the
      disease is usually between 30 and 50 years of age with variable genetic
      inheritance, although some have suggested an autosomal dominance inheritance
      pattern. Patients with AOFVD typically present with symptoms of blurred vision or
      mild metamorphopsia. Results of diagnostic testing show a normal or mildly
      subnormal electro-oculogram (EOG). Fluorescein angiography results (FA) typically
      show hypofluorescence in the area corresponding to the vitelliform lesion and a
      surrounding ring of hyperfluorescence. Results of optical coherence tomography
      (OCT) show the vitelliform lesion as being located in the retinal pigment
      epithelium (RPE) layer or between the RPE and photoreceptor layer. CASE REPORTS:
      Two cases of AOFVD are presented with each patient having different macular
      appearances owing to the different stage of the disease process. In case 1, a 76
      year-old white man presented with stage II AOFVD characterized by typical
      vitelliform lesions. His best-corrected acuities were 20/70+ in the right eye
      (O.D.) and 20/80- in the left eye (O.S.). In case 2, a 54-year-old white man
      presented with stage V AOFVD with bilateral atrophic maculae with best-corrected
      acuities of 10/60- O.D. and 10/160- O.S. CONCLUSION: Patients with adult-onset
      foveomacular vitelliform dystrophy typically have slow progressive vision loss.
      However, patients can develop dramatically decreased vision owing to subfoveal
      choroidal neovascularization (CNV). Thus, it is important to establish the
      correct diagnosis and monitor this condition. Furthermore, because there are
      reports of AOFVD having an autosomal dominance inheritance pattern with variable
      penetrance, it is recommended that the patient's family members have a
      comprehensive eye examination to rule out any early signs of this rare eye
      condition.

PMID- 16567278
TI  - Treatment of cytomegalovirus retinitis with oral valganciclovir in an acquired
      immunodeficiency syndrome patient unresponsive to combination antiretroviral
      therapy.
AB  - BACKGROUND: Cytomegalovirus (CMV) retinitis was a much-feared visual complication
      of late-stage acquired immunodeficiency syndrome (AIDS) in the past. Its
      incidence has waned significantly owing to the benefits of potent antiretroviral
      combination therapy, which for many individuals has provided some degree of
      immune reconstitution and avoidance of opportunistic infections, particularly
      this blinding disease. CASE REPORT: A 45-year-old white man with long-standing,
      multidrug-resistant human immunodeficiency virus (HIV) infection and severe
      immunodeficiency despite multiple antiretroviral drug regimens, presented to the
      eye clinic reporting decreased vision and spider web patterns in his left eye for
      the past week. Best-corrected visual acuity was 20/20 in the right (O.D.) and
      20/25 in the left eye (O.S.). Dilated funduscopic examination of the left eye
      found vasculitis of the midperipheral inferonasal arcade in the midperiphery,
      with surrounding intraretinal hemorrhage and granular retinal necrosis. Diagnosis
      of cytomegalovirus retinitis was made, and the patient began induction therapy
      with oral valganciclovir 900 mg twice a day for 3 weeks. Maintenance therapy
      after retinitis stabilization was 900 mg every day until any observed recurrence
      of infection. Three months after complete resolution of the active retinitis, the
      patient returned to the clinic reporting new floaters of recent onset. A
      reactivation of the CMV retinitis warranted a reinduction with valganciclovir 900
      mg orally twice a day for 3 weeks. CONCLUSION: This case is illustrative of the
      efficacy and relative ease of administration of valganciclovir, the newest
      medication approved for treatment and maintenance of CMV retinitis. Despite his
      severe immunodeficiency, our patient tolerated the induction and maintenance
      therapy of oral valganciclovir well, and the CMV retinitis was stabilized and
      resolved with full recovery of visual acuity.

PMID- 16567279
TI  - Decreased high-density lipoprotein serum levels associated with topical
      bimatoprost therapy.
AB  - BACKGROUND: The aim of this study is to report an adverse systemic response
      associated with topical bimatoprost therapy. CASE REPORT: An otherwise healthy 58
      year-old woman with primary open-angle glaucoma was started on bimatoprost drops
      once a day. Bimatoprost is a structural analog of prostaglandin F2 alpha
      ethanolamide (PGF2a), a class of compounds that in systemic form has been
      associated with alterations in serum lipid levels. The patient subsequently
      experienced a significant decrease in her high-density lipoprotein (HDL) serum
      levels, which subsequently returned to normal on discontinuation of bimatoprost.
      CONCLUSIONS: This is the first published report of a possible association between
      topical bimatoprost therapy and decreased serum HDL levels. Because of the
      significantly increased risk of cardiovascular disease and morbidity associated
      with low HDL levels, further study is strongly indicated.

PMID- 16567280
TI  - The crisis in health care: is it an optometric concern?
AB  - The number of uninsured and underinsured Americans continues to rise. Many large
      U.S. corporations are finding the burden of providing health insurance for their
      retirees, as well as their workers, seriously affecting their ability to compete
      globally. Many smaller companies are eliminating their health insurance entirely,
      or requiring greater contributions on the part of the insured worker. The
      problems encountered by industry have resulted in a new form of health insurance
      called Consumer-Driven Health Plans, which require greater outlays by covered
      workers. The changes in our health care delivery system in the past 42 years have
      dramatically changed the practice of optometry as well as medicine. The rapid
      growth in health care costs, particularly for our citizens who pay for their own
      health insurance, has outpaced wages by nearly 4 times. The number of citizens
      who qualify for Medicaid continues to increase. This presents a particular
      problem for optometry, as vision care is not a mandated service of Medicaid under
      federal guidelines. In addition, many managed care plans may have to eliminate
      eye care benefits, which are often a carve-out of a major plan in order to stay
      competitive. There is also evidence to suggest that many of our citizens who can
      least afford the present cost of health care will attempt to receive their care
      from community clinics and charitable programs, including vision care programs.

PMID- 16567281
TI  - Electrophysiological pulmonary vein antrum isolation with a multielectrode basket
      catheter is feasible and effective for curing paroxysmal atrial fibrillation:
      efficacy of minimally extensive pulmonary vein isolation.
AB  - BACKGROUND: How extensive should an appropriate pulmonary vein (PV) ablation be
      is a matter of controversy. OBJECTIVE: The study's aim was to investigate the
      efficacy of minimally extensive PV ablation for isolating the PV antrum (PVA)
      with the guidance of electrophysiological parameters. METHODS: Fifty-five
      consecutive symptomatic paroxysmal atrial fibrillation (PAF) patients underwent
      PV mapping with a multielectrode basket catheter (MBC). A 31-mm MBC was deployed
      in 3-4 PVs as proximally as possible without dislodgement, and the longitudinal
      PV mapping enabled us to recognize single sharp potentials formed by the total
      fusion of the PV and left atrial potentials around the PV ostium or the
      transverse activation patterns that were observed. Those potentials were defined
      as PVA potentials. Radiofrequency ablation was performed circumferentially
      targeting PVA potentials with the end point being their elimination. RESULTS:
      After circumferential PVA ablation, electrical disconnection was achieved in 77%
      and residual PVA conduction gaps were observed in 23% of all targeted PVs. Those
      residual conduction gaps were mainly located at the border between ipsilateral
      PVs (42%) and between the left PVs and left atrial appendage (33%) and were
      eliminated by a mean of 3 +/- 2 minutes of local radiofrequency deliveries.
      During the follow-up period (11 +/- 5 months), 46 (84%) patients were free of
      symptomatic PAF without any anti-arrhythmic drugs. No PV stenosis or spontaneous
      left atrial flutter occurred. CONCLUSIONS: Electrophysiological PVA ablation with
      an MBC is feasible and effective for curing PAF because this minimally extensive
      PVA isolation technique targets the optimal sites, achieving both high efficacy
      and safety.

PMID- 16567282
TI  - Multielectrode basket catheter: a new tool for curing atrial fibrillation?

PMID- 16567283
TI  - Feasibility study of endocardial mapping of ganglionated plexuses during catheter
      ablation of atrial fibrillation.
AB  - BACKGROUND: Numerous reports have demonstrated an association between autonomic
      tone and atrial fibrillation (AF). Pulmonary vein (PV) denervation during
      catheter ablation of AF has been shown to significantly reduce recurrence of AF.
      OBJECTIVES: The purpose of this study was to assess the safety and efficacy of
      high-frequency stimulation at mapping cardiac ganglionated plexuses in patients
      undergoing catheter ablation of AF. METHODS: Fourteen patients with a history of
      symptomatic AF underwent a single transseptal approach and electroanatomic
      mapping of the left atrium, right atrium, and coronary sinus. Using high
      frequency stimulation with patients under general anesthesia (20-50 Hz, 5-15 V,
      pulse width 10 ms), mapping of ganglionated plexuses was performed.
      Radiofrequency (RF) ablation was performed during AF guided by complex
      fractionated atrial electrograms. Lesions were mostly delivered circumferentially
      in the antral area of the PVs, predominantly over and adjacent to regions of
      ganglionated plexuses. RESULTS: There was a mean of 4 +/- 1 (range 2-6)
      ganglionated plexuses per patient, and a mean total of 3 +/- 1 RF applications
      were delivered over positive vagal sites. Although a vagal response occurred
      infrequently during ablation (0.9%), postablation high-frequency stimulation
      failed to provoke a vagal response in 30 (88%) of 34 previously positive vagal
      sites that underwent ablation. CONCLUSION: Ganglionated plexuses can be precisely
      mapped using high-frequency stimulation and are located predominantly in the path
      of lesions delivered during ablation of AF. Objective documentation of
      modification of autonomic tone can be documented in the majority of patients.
      Future studies are required to determine the specific role of mapping and
      targeting of ganglionated plexuses in patients undergoing catheter ablation of
      AF.

PMID- 16567284
TI  - Equivalent arrhythmic risk in patients recently diagnosed with dilated
      cardiomyopathy compared with patients diagnosed for 9 months or more.
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) recently
      expanded coverage for implantable cardioverter-defibrillators (ICDs) in patients
      with left ventricular ejection fraction < or =35% and nonischemic dilated
      cardiomyopathy for > or =9 months. To investigate the ramifications of these
      criteria, the ICD registry from Tufts-New England Medical Center was analyzed for
      arrhythmic events and death in patients with newly diagnosed (<9 months) vs late
      diagnosed (> or =9 months) nonischemic dilated cardiomyopathy. OBJECTIVES: The
      purpose of this study was to analyze the arrhythmic risk in patients with recent
      vs late diagnosis of nonischemic dilated cardiomyopathy. METHODS: One hundred
      thirty-one patients with nonischemic dilated cardiomyopathy were divided into two
      cohorts (<9 or > or =9 months of symptoms) and analyzed for any occurrence of
      treated ventricular arrhythmia, potentially lethal arrhythmias defined as
      ventricular flutter rates > or =230 bpm, and ventricular fibrillation. Patients
      with documented sustained ventricular tachycardias (included in prior CMS
      coverage) were excluded. RESULTS: In the study group, the mean age was 58.1 +/-
      15 years and ejection fraction 20.6% +/- 8%. In a follow-up period of 25.3 +/- 24
      months, the 52 patients with a recent diagnosis (1.4 +/- 2 months) had no
      difference in the occurrence of ventricular arrhythmias (P = .49) and malignant
      ventricular arrhythmias (P = .16) compared with the 79 patients diagnosed > or =9
      months (mean 58.1 +/- 39 months). CONCLUSION: Patients with nonischemic dilated
      cardiomyopathy experienced equivalent occurrences of treated and potentially
      lethal arrhythmias irrespective of diagnosis duration. These findings suggest
      that the 9-month time qualifier used in the CMS guidelines for ICD reimbursement
      may not reliably discriminate patients at high risk for sudden cardiac death in
      this selected population.

PMID- 16567285
TI  - Recently diagnosed nonischemic dilated cardiomyopathy: when should we implant the
      defibrillator?

PMID- 16567286
TI  - Prospective validation of stress echocardiography as an identifier of cardiac
      resynchronization therapy responders.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) provides benefit for
      congestive heart failure (CHF), but predictors of the clinical response are
      debated. OBJECTIVE: The aim of this prospective study was to assess the
      predictive role of dobutamine stress echocardiography (DSE) in identifying a
      suitable candidate for CRT. METHODS: From March 2001 to December 2003, 71 CHF
      patients were prospectively enrolled on the basis of four criteria: New York
      Heart Association (NYHA) class III and IV; QRS > or =150 ms with a left bundle
      branch block pattern, and left ventricular ejection fraction (LVEF) < or =35%
      under optimal medical treatment. The combined endpoints were hospital readmission
      for class IV CHF, heart transplant (HT), and CHF-related death. RESULTS: The 67
      patients completing the study presented with the following characteristics: age
      (70 +/- 10 years; 11 women); etiology (idiopathic in 44, ischemic in 23); NYHA
      class (40 in class III and 27 in class IV); LVEF 26% (+/-5%); QRS duration (190
      +/- 28 ms); 6-minute walk test 330 m (+/-108); peak oxygen uptake 10.7 (+/-3.3
      mL/kg/min); mitral insufficiency in 42 (> or =III grade); interventricular (IV)
      delay (62 +/- 21 ms); and intraventricular dyssynchrony in 30 patients. Over the
      follow-up period of 12.1 +/- 8.7 months, 20 (29.9%) of 67 patients presented with
      at least one hemodynamic event: hospitalization for CHF in 19 (28%) of 67, HT in
      2 (3%) of 67, and CHF death in 7 (10%) 67. Univariate analysis identified NYHA
      class (P = .03), LVEF (P = .015), IV dyssynchrony before (P = .038) and after CRT
      (P = .0035), IV delay after CRT (P = .002), 6-minute walk distance (P = .01), and
      DSE Res+ (P = .008) as significant predictors of clinical events. A receiver
      operating curve established a cut-off value of 1.25 for the DSE responders (Res+:
      34 patients at 10 microg/kg/min infusion rates), and the improvement at the 10
      microg/kg/min level was 41% +/- 7% in Res+ and 29% +/- 8% in nonresponders
      (P<.0001). With a cut-off value of 1.25-fold the LVEF increase, the DSE test
      exhibits 70% sensitivity, 61.7% specificity, 43.8% positive predictive value, and
      82.9% negative predictive value. Cox analysis identified IV dyssynchrony before
      CRT (P = .01) and DSE Res+ (P = .003) as independent predictive factors.
      CONCLUSIONS: Independent predictive factors of severe hemodynamic clinical
      outcome in patients with CRT are IV dyssynchrony and DSE.

PMID- 16567287
TI  - Myocardial contractile reserve as a predictor of cardiac resynchronization
      therapy response.

PMID- 16567288
TI  - Differentiating arrhythmogenic right ventricular cardiomyopathy from right
      ventricular outflow tract ventricular tachycardia using multilead QRS duration
      and axis.
AB  - BACKGROUND: Ventricular tachycardia (VT) resulting from arrhythmogenic right
      ventricular cardiomyopathy (ARVC) may be difficult to differentiate from
      idiopathic right ventricular outflow tract (RVOT) VT. OBJECTIVES: The purpose of
      this study was to investigate the hypothesis that QRS characteristics would be
      different in ARVC because of altered conduction through abnormal myocardium.
      METHODS: In 24 RVOT VT patients (18 women and 6 men; age 42 +/- 10 years) and 20
      ARVC patients (12 women and 8 men; age 38 +/- 14 years), mean QRS duration,
      frontal plane axis, and precordial R-wave transition were measured in 12-lead
      ECGs recorded during VT. RESULTS: Mean QRS duration was longer in all 12 leads in
      ARVC patients. A significant difference was noted in leads I, III, aVL, aVF,
      V(1), V(2), and V(3) (P <.05). Leads I and aVL had the largest mean difference
      between ARVC and RVOT VT patients of 17.6 +/- 4.7 ms and 15.8 +/- 7.5 ms,
      respectively (P <.0001). Lead I QRS duration > or =120 ms had a sensitivity of
      100%, specificity 46%, positive predictive value 61%, and negative predictive
      value 100% for ARVC. The area under the receiver operating characteristic (ROC)
      curve was 0.89. The addition of mean QRS axis <30 degrees (R<S in lead III) to
      the above criterion increased specificity for ARVC to 100%. QRS duration remained
      sensitive and specific in the subgroup of nine ARVC ECGs with an inferior axis
      (ROC area 0.82). R-wave transition was not different between groups. CONCLUSION:
      QRS duration is longer in ARVC compared with RVOT VT. An algorithm combining lead
      I QRS duration for sensitivity and axis for specificity is useful for
      differentiating the two tachycardia substrates.

PMID- 16567289
TI  - QT peak dispersion, not QT dispersion, is a more useful diagnostic marker for
      detecting exercise-induced myocardial ischemia.
AB  - BACKGROUND: The electrocardiographic indices of QT dispersion (QTd), QT peak
      dispersion (QTpd), and the principal component analysis ratio (PCAr) are related
      to the occurrence of fatal arrhythmia and are influenced by physical exercise.
      OBJECTIVE: The purpose of this study was to investigate whether or not the QT
      parameters can be used as markers for exercise-induced myocardial ischemia.
      METHODS: We measured these QT parameters at rest and at 3 minutes after exercise
      using exercise-stress thallium-201 scintigraphy (SPECT), compared with
      conventional ST segment changes in 161 patients with suspected or known coronary
      artery disease. The patients were classified into four groups (normal,
      redistribution, fixed defect, and redistribution with fixed defect) according to
      SPECT. RESULTS: At rest, QTd and PCAr were greater in the fixed defect and
      redistribution with fixed defect groups. PCAr, however, increased after exercise
      in the redistribution and redistribution with fixed defect groups. Although QTpd
      at rest was not significantly different among the four groups, it increased in
      the redistribution and redistribution with fixed defect groups after exercise
      (QTpd after exercise: normal, 36 +/- 16 ms vs. redistribution, 51 +/- 23 ms,
      redistribution with fixed defect, 53 +/- 19 ms; P<.05). For myocardial infarction
      reflected by fixed defect, QTd at rest was the most useful indicator, while QTpd
      after exercise was the most useful indicator for exercise-induced myocardial
      ischemia according to multiple logistic regression analysis with receiver
      operating characteristic curves. In addition, the change in PCAr by exercise was
      an independent predictor for exercise-induced ischemia. CONCLUSIONS: QTpd and
      PCAr could be useful indices for exercise-induced myocardial ischemia.
      Determining the QTpd of a patient after exercising can improve the diagnostic
      accuracy of ischemia in a routine clinical setting.

PMID- 16567290
TI  - Should QT replace ST for detecting myocardial ischemia?

PMID- 16567291
TI  - The benefit of upgrading chronically right ventricle-paced heart failure patients
      to resynchronization therapy demonstrated by strain rate imaging.
AB  - BACKGROUND: RV pacing induces conduction delay (CD), mechanical dyssynchrony, and
      increased morbidity in patients with HF. CRT improves HF symptoms and survival,
      but sparse data exist on its direct effect on chronically RV-paced HF patients.
      OBJECTIVES: To assess the benefit of cardiac resynchronization therapy (CRT) in
      chronically right ventricle (RV)-paced heart failure (HF) patients. METHODS: We
      studied 12 consecutive patients with class III HF who had a previously implanted
      pacemaker or implantable cardioverter-defibrillator. These individuals were
      chronically RV paced and referred for upgrade to a biventricular device by their
      primary cardiologists. Tissue Doppler and strain rate imaging (TDI and SRI,
      respectively) were performed immediately before each upgrade and 4-6 weeks
      afterward to quantify changes in regional wall motion and synchrony with CRT.
      RESULTS: CRT significantly reduced the mean QRS duration (205 ms to 156 ms;
      P<.0001), and it increased the ejection fraction (30.7%+/-5.1% to 35.8%+/-5.1%;
      P<.01). Left ventricular end-systolic and end-diastolic dimensions were also
      significantly reduced. Clinically, patients improved by an average of one New
      York Heart Association (NYHA) functional class after upgrade (P = .006). The
      parameter exhibiting greatest improvement was the coefficient of variation (CoV:
      standard deviation/mean) of time to peak systolic strain rate, a marker of
      ventricular dyssynchrony, which decreased from 34.3%+/-13.0% to 19.0%+/-6.6%
      (P<.01). Reduction in CoV of time to peak systolic strain rate was maximally seen
      in the midventricle (38.2%+/-19.6% to 16.5%+/-9.7%; P<.01). CONCLUSIONS:
      Upgrading chronically RV-paced HF patients to CRT improves global and regional
      systolic function. TDI and SRI provide compelling evidence that this benefit
      parallels that seen in HF patients with CD unrelated to RV pacing, which implies
      that biventricular pacing synchronizes mechanical activation in different
      myocardial regions in patients upgraded from RV pacing as well.

PMID- 16567292
TI  - Smokers are at markedly increased risk of appropriate defibrillator shocks in a
      primary prevention population.
AB  - BACKGROUND: Cigarette smoking is a known risk factor for sudden cardiac death
      (SCD). It is unknown whether smoking status affects implantable cardioverter
      defibrillator (ICD) therapy. OBJECTIVE: The primary end point was appropriate ICD
      therapy according to smoking status. METHODS: A total of 105 consecutive patients
      who underwent ICD implantation for primary prevention of SCD were retrospectively
      analyzed. All patients had an abnormal response to programmed ventricular
      stimulation performed for nonsustained ventricular tachycardia in the setting of
      ischemic cardiomyopathy between January 1999 and December 2003. RESULTS: Among
      the 105 patients, 6 (37.5%) of 16 current smokers, 14 (25.9%) of 54 former
      smokers, and 2 (5.7%) of 35 of never smokers received an appropriate ICD therapy
      (P = .02). Kaplan-Meier analysis for survival free of appropriate ICD therapy
      comparing never smokers with both current smokers (P = .002) and former smokers
      (P = .01) demonstrated statistically significant differences by log rank over a
      mean follow-up of 21.8 +/- 13.7 months. Cox regression analysis found that
      current smoking was associated with an increased risk of appropriate therapy
      (hazard ratio 7.36; 95% confidence interval 1.42-38.10; P = .02) as was former
      smoking (hazard ratio 5.42; 95% confidence interval 1.20-24.47; P = .03). There
      was no difference in inappropriate therapy between groups (P = .12). CONCLUSIONS:
      Cigarette smoking is an independent predictor of appropriate ICD therapy in a
      primary prevention population. While outcomes differences among current smokers,
      former smokers, and never smokers are demonstrable, the effect of smoking
      cessation on ICD therapy requires further study.

PMID- 16567293
TI  - Smoking accelerates implantable cardioverter-defibrillator shocks: encouraging
      patients to quit a bad habit.

PMID- 16567295
TI  - Is skeletal myoblast transplantation proarrhythmic? The jury is still out.

PMID- 16567296
TI  - Idiopathic ventricular tachycardia originating in the great cardiac vein.

PMID- 16567294
TI  - Electrophysiological consequence of skeletal myoblast transplantation in normal
      and infarcted canine myocardium.
AB  - OBJECTIVE: The purpose of this study is to test our hypothesis that injection of
      skeletal myoblasts (SkMbs) into viable tissue may alter impulse conduction but
      that injections into nonviable tissue (scar) will have negligible impact.
      BACKGROUND: Myocardial infarction (MI) is a major public health problem. SkMb
      transplantation after MI has been shown to have some beneficial effect on
      hemodynamic function. Previous studies have indicated that SkMbs do not
      electrically couple with viable host myocardium in vivo. METHODS: We used optical
      mapping to measure impulse propagation and arrhythmia inducibility in the canine
      left ventricular wedge preparation with and without MI. MI was created by
      temporary ligation of a branch of the left anterior descending coronary artery
      (LAD) (7.0 +/- 3.8 ng/mL troponin 24 hours after MI). Labeled SkMbs (10(8) in 4
      mL of serum-free basal solution) were injected from the epicardium (20-40 0.1 mL
      injections) into normal myocardium (n = 8) or the central zone of the MI (n = 6).
      RESULTS: During endocardial pacing in the absence of MI, transmural conduction
      velocity was similar with (35.75 +/- 3.4 cm/s) and without (37.42 +/- 3.6 cm/s)
      SkMb transplantation. However, pacing from the epicardium resulted in conduction
      slowing in regions that were DiI-positive and associated with the expression of
      skeletal myosin (fast) but not connexin-43. In all preparations with MI (n = 13),
      abnormal impulse propagation was seen regardless of SkMb transplantation.
      Arrhythmias (at least one extra beat after standard programmed stimulation)
      occurred most frequently in preparations with MI independent of SkMb
      transplantation. In preparations without MI (n = 8), SkMb transplantation did not
      significantly increase arrhythmia inducibility. CONCLUSION: We conclude that
      SkMbs transplanted into normal myocardium can cause abnormal impulse propagation.
      These data suggest that the location of SkMb transplantation may influence
      arrhythmia vulnerability associated with MI.

PMID- 16567297
TI  - Tale of two tails: the tip of the atrial appendages is an unusual site for focal
      atrial tachycardia.

PMID- 16567298
TI  - The National ICD Registry: now and into the future.

PMID- 16567299
TI  - Echocardiography and patient selection for cardiac resynchronization therapy: a
      critical appraisal.
AB  - Echocardiography has been the focus of growing interest for improving patient
      selection for cardiac resynchronization therapy in order to reduce the number of
      nonresponders. Various techniques have been described for assessing dyssynchrony,
      using standard echocardiography (pulsed-wave Doppler and M-mode
      echocardiography), tissue Doppler imaging, and other imaging modes such as three
      dimensional echocardiography. This article provides an overview of the technical
      and practical aspects of these different techniques and discusses the current
      evidence for optimizing patient selection by echocardiography.

PMID- 16567300
TI  - Wilhelm His Jr. (1863-1934)--the man behind the bundle.
AB  - Wilhelm His Jr. (1863-1934) was a Swiss-born cardiologist and anatomist. In 1893,
      he discovered the bundle of His-the specialized tissue in the heart that
      transmits the electrical impulses and helps synchronize contraction. He pioneered
      studies in cardiac conduction and coined the term "heart block," which he
      identified as the cause of Adams-Stokes disease. He was a professor of medicine
      at the University of Berlin, became the dean of medicine in 1918 and in 1928 was
      elected rector of the University of Berlin. Through his long clinical and
      teaching career he became better known for his work on gout and diseases of the
      joints. "Trench fever," or Werner-His disease, was also named after him. This
      report presents the life and work of Wilhelm His Jr., who was described by his
      colleagues as "a master of his profession, a great physician, investigator, and a
      well cultured gentleman."

PMID- 16567301
TI  - Is there a role for amiodarone in the era of the implantable cardioverter
      defibrillator?

PMID- 16567302
TI  - Atrioventricular block: what is the mechanism?

PMID- 16567303
TI  - Supraventricular tachycardia vs ventricular tachycardia: what is the rhythm?

PMID- 16567304
TI  - How to manage the patient with a high defibrillation threshold.

PMID- 16567305
TI  - Large septic pulmonary embolism complicating extraction of an infected
      transvenous defibrillator lead.

PMID- 16567306
TI  - In Memoriam: Gregory R. Ferrier, PhD, 1943-2005.

PMID- 16567307
TI  - Seymour Furman, M.D. 7-12-1931 - 2-20-2006.

PMID- 16567309
TI  - Primary biliary cirrhosis: when and why does the disease develop?
AB  - Primary biliary cirrhosis is a chronic cholestatic liver disease with an
      autoimmune pathogenesis, that generally develops in adult life, often in
      perimenopausal age. The clinical features are heterogeneous, ranging from an
      asymptomatic presentation to end-stage liver disease. Primary biliary cirrhosis
      is unknown in children and its natural history has yet to be elucidated.
      Following a Canadian report of primary biliary cirrhosis in two girls (16 and 15
      years old), we describe a clinical case developing at 17 years of age. A temporal
      association between Borrelia Burgdorferi infection and diagnosis of primary
      biliary cirrhosis was observed.

PMID- 16567310
TI  - Cardiotoxicity of 5-fluorouracil in 1350 patients with no prior history of heart
      disease.
AB  - To show the nature and magnitude of EKG anomalies subsequent to 5-fluorouracil
      (5FU) administration and determine whether the onset is dependent on a pre
      existing cardiovascular pathological condition. 1,350 patients were treated by
      5FU between 1995 and 2000. EKG were recorded in all patients before each
      administration of 5FU. All cases of 5FU related cardiotoxicity were analyzed and
      recorded by the Lyon Pharmacovigilance Center. Clinical symptoms included chest
      pain in 10 patients with an infarct-like pattern in 2 (including one death), and
      heart failure in one. Three patients suffered from anginal pain without EKG
      changes and two had electrocardiographic changes without clinical symptoms.
      Coronary disorders resolved completely on cessation of 5FU therapy, except in one
      patient who died two months later of heart infarct. The patient with heart
      failure required specific treatment. Based on both the clinical and
      electrocardiographic changes, the causative role of 5FU is highly likely. The
      incidence of cardiotoxicity was 1.2% among these patients, which is close to
      previous data from the literature. These 16 case reports confirm the cardiotoxic
      potential of 5FU and argue for the need of a careful cardiac monitoring of 5FU
      treated cancer patients. The mechanism of 5FU cardiotoxicity is not elucidated.
      Coronary spasm is the most commonly suspected hypothesis, but further studies are
      warranted to seek for toxic inflammatory lesions of the myocardium (apoptosis,
      necrosis, fibrosis).

PMID- 16567311
TI  - [Cancer cells escape from failsafe programs in a simple Twist].
AB  - A major obstacle to the expansion of abnormal cells with significant
      proliferative potential is the induction of either cellular senescence or
      programmed cell death. Consequently, oncogene-driven hyperproliferation must be
      associated with apoptosis inhibition to allow malignant outgrowth. The oncogenic
      cooperation of N-Myc and Twist 1 in the development of neuroblastoma, the most
      common and deadly solid tumour of childhood, perfectly illustrates such a
      process. N-Myc promotes cell proliferation whereas Twist 1 counteracts its pro
      apoptotic properties by knocking-down the ARF/p53 pathway. This observation
      provides a mechanistic explanation for the rarity of p53 mutations in
      neuroblastomas. It also highlights the involvement of two crucial regulators of
      embryogenesis in human cancer development. In this review, we discuss the
      possible role of Twist 1 in tumour progression, based on the numerous recent
      studies reporting its overexpression in a variety of human cancers.

PMID- 16567312
TI  - [Adjuvant chemotherapy in the treatment of sarcomas].
AB  - For many types of cancers, adjuvant chemotherapy showed a moderate but
      significant benefit in terms of survival improvement. In sarcomas, the situation
      is contrasted and depends on the histological, molecular sub-types, as well as
      the topography of the tumor. Soft tissue sarcomas are in general poorly
      chemosensitive tumors and while adjuvant chemotherapy was found effective to
      delay relapses or to decrease the local relapses, it failed to yield a
      significant benefit with regard to overall survival. Sub-groups analysis indicate
      a significant lengthening of survival for the soft tissues sarcomas of the
      extremities. Neoadjuvant chemotherapy of the soft tissues sarcomas starts should
      be reserved to rhabdomyosarcomas and the bone sarcomas like the osteosarcomas and
      the Ewing's sarcomas of bones are more susceptible to chemotherapy, which is an
      integral part of the treatment with a preoperative chemotherapy and, following
      surgery of the primary tumor, an adjuvant chemotherapy adapted to the
      histological response to the neoadjuvant treatment.

PMID- 16567313
TI  - [Medical treatment of metastatic or recurrent cancer of the cervix].
AB  - Cervical cancer is the most frequent gynaecological cancer worldwide. Incidence
      is decreasing in industrialized countries but remains high in poorest countries.
      In metastatic or recurrent disease, the treatment is more often palliative.
      Chemotherapy yields some efficiency in non-irradiated fields but the benefit
      should be balanced with the treatment toxicities. In this setting, cisplatin is
      considered as the drug of reference, but responses rates are poor. So far,
      combined chemotherapy has not been shown better than cisplatin alone. Recently,
      results for cisplatin associated with topotecan appear to be promising while used
      for treatment in metastatic or recurrent disease. However, the bad prognosis of
      this illness leads to keep on looking for better treatments. Targeted
      therapeutics and immunotherapy against human papilloma virus could bear
      significant progress for treatment of cervical cancer.

PMID- 16567315
TI  - [Parathyroid carcinoma].
AB  - Parathyroid carcinoma is a rare disease accounting for 1 to 5% of parathyroid
      neoplasms. This malignant tumour must be suspected when a severe primary
      hyperparathyroidism occurs with high hypercalcemia and elevated parathormon
      levels. At this time, a cervical mass is often palpable. Both head and neck
      ultrasonography and 99mTc-sestamibi scintigraphy are the best preoperative
      imaging tests to suspect and localize the tumour. Surgical approach with
      simultaneous tumorectomy and hemithyroidectomy, completed by selective neck
      dissection (level VI) is the treatment of choice. An elective lateral neck
      dissection should be performed if necessary. Tumour control should be monitored
      by regular measurement of calcium and parathormon levels. Local recurrence or
      metastasis risk is 30 to 70% and the 5 year overall survival about 50 to 80%. In
      case of recurrence, aggressive surgical management should be applied and adjuvant
      radiation therapy may be discussed.

PMID- 16567314
TI  - [Treatment of venous thrombosis in cancer patients: practical aspects].
AB  - The risk of venous thromboembolism (VTE) is increased in association with
      malignancy, and has a potential to produce significant morbidity and mortality.
      Treatment of such patients with anticoagulants is associated with both benefit
      and a high rate of complications. In the early phase, the treatment is usually
      achieved with low molecular weight heparin (LMWH), which has a number of
      advantages over unfractionated heparin (UFH): once or twice daily administration,
      no necessary laboratory monitoring, lesser risk of bleeding and no drugs
      interactions. Nevertheless, the UFH is the anticoagulant of choice when a rapid
      anticoagulant effect or stop of anticoagulant effect is required, in the
      treatment of massive pulmonary embolism or severe renal insufficiency. Prolonged
      anticoagulation with LMWH (over 3 or 6 months) appears to be beneficial on
      survival for such patients. The subject of anticoagulation in patients with
      primary or secondary brain tumours is controversial. The long-term
      anticoagulation mainly use LMWH or vitamin K antagonist. The last ones are more
      difficult to use because of an unpredictable response with higher rate of
      recurrence and bleeding. The optimal duration of treatment is not known but the
      patients should be treated for at least 6 months, even at least 12 months after a
      second episode of venous thromboembolism. On the primary prevention in high-risk
      surgical oncology, the LMWH are at least as effective and safer as UFH when the
      optimal dose was administered. For the medical patients, the use of prophylactic
      anticoagulant treatment is less clear except the patients who are bedridden for
      prolonged periods of time. For the secondary prevention, the LMWH seems to be
      more effective over vitamin K antagonists. For these patients, the anticoagulant
      therapy is recommended indefinitely or until cancer is resolved.

PMID- 16567316
TI  - [Stress and allostatic load: perspectives in psycho-oncology].
AB  - Since its origins as a scientific field back in the late seventies, psycho
      oncology has remained notably descriptive. Few conceptual advances have been
      achieved in the study of psychodynamics and biological underpinnings of
      psychological adjustment to the experience of cancer. Moreover, the specific
      aspects of psychopathological responses to cancer, as well as their optimal
      pharmacological management remain poorly understood. On the other hand, recent
      years have been characterized by significant progress in the delineation of
      biological mechanisms of stress and its consequences for the brain, body, and
      general health. In this paper, we examine the applicability of the concept of
      allostatic load to the study of stress and psychopathology related to the cancer
      experience. While homeostasis refers to maintaining specific biological
      parameters constant, allostasis can be defined as the process of maintaining
      stability through change. In this context, excessive or dysregulated activity of
      allostatic (adaptive) systems leads to deleterious effects for the brain (reduced
      neurogenesis, altered cell death processes, and dendritic branching) and body
      (increased cardiovascular risk). These damaging effects of cumulated stress have
      been refered to as the allostatic load, or the cost inflicted to the organism in
      order to maintain stability. We hypothesize that the concept of allostatic load
      is particularly relevant to the multiple, repeated and chronic stressors
      associated with the experience of cancer. In the light of this model, we propose
      a new classification of psychopathological conditions in psycho-oncology: the
      cancer-specific stress syndrome, with its three clinical subtypes (depressive,
      post-traumatic, and dysallostatic). Suggestions are formulated for some
      biological correlates of psychodynamic processes and for the study of innovative
      pharmacological approaches in the treatment of stress-related disorders in
      oncology (anticonvulsants, CRH antagonists, 5HT-1A receptor agonists...).

PMID- 16567317
TI  - [Genetic polymorphism of gluthation-S transferases and N-acetyl transferases 2
      and nasopharyngeal carcinoma: the Tunisia experience].
AB  - Interindividual differences observed in the metabolism of xenobiotics have been
      attributed to the genetic polymorphism of genes, which code for enzymes involved
      in detoxification. This genetic variability seems to be associated with the
      individual's susceptibility to certain cancers, including nasopharyngeal
      carcinoma. In this study, we have investigated the genotypic frequencies of DNA
      polymorphisms of two detoxification's genes: the gluthatione-S-transferase (GST)
      and the N-acetyl transferase 2 (NAT2). The study has included 45 patients with
      nasopharyngeal carcinoma compared to 100 healthy Tunisian controls. The presence
      of the GSTM1 null and GSTT1 null polymorphism was screened by using a multiplex
      PCR procedure. A PCR-RFLP method was used to detect polymorphism for the most
      common alleles of the NAT2 gene. Allelic frequencies between the two groups were
      compared using a chi2 test and odds ratio with 95% confidence intervals were
      calculated. The results indicate that the genotypic frequency of GSTM10/0 between
      controls and patients was significantly different. This genotype confers an
      increased risk of nasopharyngeal carcinoma (Odds Ratio = 2.12, [0.64-4.7]).
      However, genotypic frequencies of NAT2*6/NAT2*6 were significantly higher in the
      group of nasopharyngeal carcinoma patients. The calculated Odds Ratio showed an
      association between this genotype and nasopharyngeal carcinoma. In conclusion,
      the increase of nasopharyngeal carcinoma risk in Tunisia seems to be associated
      with GSTM10/0 and NAT2*6/6 genotype.

PMID- 16567318
TI  - [Influence of the delay between conservative surgery and radiation therapy on
      local relapse in node-positive breast tumor].
AB  - It has been shown that a delay in radiotherapy (RT) initiation resulted in a
      higher local relapse (LR) rate. The present analysis investigated retrospectively
      if the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS)
      after breast-conserving surgery (BCS) in node-positive (N +) breast cancer
      patients. Among seven French Adjuvant Study Group trials, 1,831 patients were
      assessable: 475 received RT directly after BCS, 567 after the 3rd chemotherapy
      (CT) cycle, and 789 after the 6th CT cycle. In the 1,356 patients receiving CT,
      it consisted of FEC regimens (fluorouracil, epirubicin, cyclophosphamide) in
      83.5% of patients. After a 102-month median follow-up, 214 patients (11.7%)
      developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively
      (p < 0.0001). In the multivariate analysis, the timing of RT was not associated
      with a higher rate of LR, whereas tumor size and hormonotherapy were prognostic
      factors. In our population, there was no increase in the risk of LR when RT was
      delayed to deliver adjuvant CT. Prognostic factors were tumor size, and
      hormonotherapy. The number of CT courses could modify this risk.

PMID- 16567319
TI  - [Multisite validation study of questionnaire assessing out-patient satisfaction
      with care questionnaire in ambulatory chemotherapy or radiotherapy treatment].
AB  - Patient satisfaction is now recognised as an important quality of care outcome
      which is particularly relevant in oncology. Adapted from the EORTC In-Patsat32,
      the Out-Patsat35 is a 35-item satisfaction with care questionnaire measuring
      cancer outpatients' perception of hospital doctors and nurses, as well as aspects
      of care organisation and services. This study assessed the psychometric
      properties of this scale. Patients undergoing ambulatory chemotherapy (CT) or
      radiotherapy (RT) in 7 cancer centres in France were invited to complete at home
      the Out-Patsat35 as well as EORTC QLQ-C30 for psychometric testing. Of 416
      eligible patients recruited, 96% returned the questionnaire. Most patients (71%
      in CT; 69% in RT) completed this scale within 15 minutes and the mean rate of
      item omission was only 4.4%. Confirmatory analyses revealed good convergent
      validity and excellent internal consistency, although some subscales within the
      Out-Patsat35 were relatively highly correlated. Items and subscales of the Out
      Patsat35 and of the QLQ-C30 were not significantly correlated, underlying that
      the two questionnaires are assessing quite distinct concepts. The subscales of
      the Out-Patsat35 were not related to age, gender and education, suggesting a
      cultural evolution in French cancer patients towards a greater homogeneity in
      their opinion toward care. This study supports the acceptability to patients, and
      the psychometric properties of the EORTC Out-Patsat35 questionnaire.

PMID- 16567320
TI  - Descriptions of clinical semiology of seizures in literature.
AB  - Literary texts are an important part of the cultural history of many fields of
      medicine. Accounts of epilepsy are frequent, and descriptions of seizure
      semiology are often included with varying detail. This review looks at these, and
      considers the authors' background knowledge of epilepsy. The first group of
      writers suffered seizures themselves. Some of them provide remarkable and novel
      insights into the subjective symptoms and experiences in and around seizures.A
      second group draws from their own observations of seizures in others who may have
      been close relatives or fortuitous strangers. Here, the outside view prevails,
      and seizures may be described with clinical objectiveness. Commonly, the
      reactions of onlookers become part of the narrative beyond the seizure
      description. The third group writes from second-hand knowledge, which may be
      other observer reports, interviews with people with epilepsy or with experts,
      information being available in dictionaries, medical textbooks and the like. The
      professional standard of most writers means that the resulting descriptions are
      quite accurate, but there are also examples of poor use of such information. Many
      authors' sources are not known, but can be assumed to belong to one of the above
      categories, and we can sometimes guess. It appears that even authors with no
      first-hand knowledge are often aware of seizure types other than the most widely
      known, generalised tonic-clonic, and there is a widespread interest in warnings
      and how the afflicted respond to them. The quality of an author's fictional
      account of epilepsy should not be judged from a translation, because specific
      aspects and the language involved in the description may have been misunderstood
      by the translator.

PMID- 16567321
TI  - Cognitive functions in children with benign childhood epilepsy with
      centrotemporal spikes (BECTS).
AB  - Benign childhood epilepsy with centrotemporal spikes (BECTS) is regarded as a
      benign form of epilepsy because of its usually favorable outcome, in terms of
      seizures. Eighteen children with BECTS were studied in terms of
      neuropsychological and learning abilities: intellectual quotient, oral language
      (phonological production, naming skills, verbal fluency and syntactic
      comprehension), drawing and visuo-spatial skills, visual and selective attention,
      verbal and visuo-spatial memory, reading, numeracy and spelling. The mean IQ of
      the population was within the normal range, but individual results were
      heterogeneous. Verbal functions and memory were normal. In contrast, drawing and
      visuo-spatial skills, attention and visuo-spatial memory were significantly weak
      compared to the normal range for age. Reading, numeracy and/or spelling ability
      were significantly delayed by one academic year or more in ten of the children.
      In conclusion, despite its benign outcome in terms of epilepsy, BECTS can be
      accompanied by specific cognitive disorders and low academic achievement.

PMID- 16567322
TI  - The consequences of idiopathic partial epilepsies in relation to
      neuropsychological functioning: a closer look at the associated mathematical
      disability.
AB  - Although the seizure prognosis is mostly favorable in idiopathic partial
      epilepsies, there is some empirical evidence showing that subtle
      neuropsychological impairments, with a consequent risk of academic
      underachievement, are not rare. We investigated neuropsychological functioning
      including attention, memory, visuomotor ability, and executive functioning with a
      closer look at the associated mathematical ability in patients with idiopathic
      partial epilepsies. A battery of age-appropriate, neuropsychological and
      mathematics achievement tests was administered to 30 participants with idiopathic
      partial epilepsy [13 children with benign epilepsy with centrotemporal spikes
      (BECTS), 17 children with idiopathic childhood occipital epilepsies (ICOE)], and
      to 30 healthy participants matched for age, sex, handedness, and socioeconomic
      status. Results did not support any impairment in overall neuropsychological
      functioning in participants with idiopathic partial epilepsies, whereas, isolated
      deficits did exist. The mean performance of the IPE group was significantly lower
      than the control group in six out of 12, neuropsychological measures: drawing (p
      < 0.01), digit span (p < 0.05), verbal learning (p < 0.01), object assembly (p <
      0.01), similarities (p < 0.05), and vocabulary (p < 0.001). Results suggested
      that one should be cautious regarding neuropsychological and academic prognosis
      in the so-called benign idiopathic partial epilepsies of childhood.

PMID- 16567323
TI  - Oligogenic inheritance in photosensitive juvenile myoclonic epilepsy?
AB  - The interplay of multiple genetic factors, as opposed to monogenic inheritance,
      is suspected to play a role in many idiopathic generalized epilepsies. This leads
      to a digenic or oligogenic inheritance model, which although rather simplified,
      may explain at least some of the clinical observations. Here we describe a family
      in which the clinical phenotype in the offspring can be explained by a
      combination of photosensitivity and epilepsy traits that segregated independently
      of each other. This case history demonstrates the need to evaluate family
      histories in more detail in order to uncover potential clinical markers for
      genetic factors in complex epilepsies.

PMID- 16567324
TI  - Identifying baseline characteristics of placebo responders versus nonresponders
      in randomized double-blind trials of refractory partial-onset seizures.
AB  - In add-on studies of partial-onset seizures, the placebo response, defined as a
      50% decrease from baseline in seizure frequency, ranges from 0-19%. Reasons for
      this significant difference between placebo groups in different trials are not
      given in the literature. This exploratory analysis was undertaken to compare the
      baseline characteristics of placebo responders and nonresponders, in an attempt
      to identify common features. The pooled statistical analysis was performed on the
      database for three pivotal studies of levetiracetam (n = 904). Using the 50%
      response definition, we found that 45.6% of placebo nonresponders were on one
      antiepileptic drug at baseline, compared with 69% of placebo responders. The
      difference in number of baseline antiepileptic drugs was almost statistically
      significant (p = 0.056). Placebo nonresponders also tended to have epilepsy for
      longer than responders. The mean age at onset of epilepsy was consistently
      different between placebo nonresponders and responders (15.2 versus 20.8 years,
      respectively; p = 0.019). These findings suggest that the placebo response is
      higher in patients with partial-onset seizures who are taking only one
      antiepileptic drug at baseline and have later onset and shorter duration of
      epilepsy than in patients on more than one antiepileptic drug at baseline with
      earlier onset and longer duration of epilepsy.

PMID- 16567325
TI  - Isolated paroxysmal arousals as focal epilepsy.
AB  - Paroxysmal motor phenomena and arousals during sleep are frequent. The
      differential diagnoses between benign hypnic transient events, epileptic and non
      epileptic seizures represent a common clinical problem. Video-EEG monitoring
      during sleep, recording several episodes in the same patient, is essential in
      order to characterize these phenomena. It offers the possibility to compare
      electro-clinical data, to demonstrate the eventual stereotyped pattern of motor
      phenomena and their progression in time, and to study EEG-polygraphic correlates.
      The recently described double split-screen synchronized display (DSSSD) technique
      represents a useful tool for comparing particular clinical patterns of epileptic
      seizures when dealing with complex, hypermotor phenomena observed in frontal lobe
      epilepsy. We reviewed the data of 24 patients admitted during a two-year period
      (2002-2003) to our epilepsy sleep unit for isolated paroxysmal sleep motor
      events. Four patients presented with very brief paroxysmal arousals without
      daytime fits. Three of our patients presented isolated paroxysmal arousals,
      whereas in one, the events were associated with hypermotor seizures. We present a
      simplified variant of the DSSSD method (modified DSSSD) that can be used to study
      episodes of paroxysmal arousals in order to confirm their stereotyped motor
      pattern. The clinical aspects and the EEG-polygraphy patterns were informative,
      with the absence of asymmetrical tonic or dystonic posturing of the limbs. Scalp
      EEG alone does not usually provide much information in patients with isolated
      paroxysmal arousals. Coupled to the modified DSSSD technique, it may allow
      confirmation of the diagnosis of frontal epilepsy, as was the case in our four
      patients. [Published with video sequences].

PMID- 16567326
TI  - EEG and seizure exacerbation induced by carbamazepine in Panayiotopoulos
      syndrome.
AB  - We report on a 4-year 8-month-old boy with Panayiotopoulos syndrome who showed
      atypical evolution with newly developed absence seizures and EEG exacerbation
      induced by carbamazepine. Soon after the introduction of carbamazepine, EEGs
      began to worsen, and finally absence seizures and myoclonic seizures appeared.
      Immediately after we discontinued carbamazepine, the seizures disappeared and the
      EEG improved. Carbamazepine may induce unusual electroclinical features,
      electrophysiologically explained by bilateral synchrony. This case provides more
      evidence of the close links between Panayiotopoulos syndrome and benign childhood
      epilepsy with centrotemporal spikes.

PMID- 16567327
TI  - Herpes encephalitis as a cause of nonconvulsive status epilepticus.
AB  - Nonconvulsive status epilepticus is a specific form of status epilepticus
      characterized by alteration in mental status and persistent seizure activity on
      EEG, with or without motor phenomena. Recognition of the consequences of
      nonconvulsive status epilepticus has attracted greater attention to this
      condition. We present a 24-year-old woman with epilepsy who developed
      nonconvulsive status epilepticus during pregnancy. Despite treatment with
      antiepileptic drugs, the seizures persisted and confusion deepened. Further
      workup to explain the etiology revealed the diagnosis as herpes encephalitis. She
      recovered completely by the third day of parenteral acyclovir administration.
      Herpes simplex encephalitis causing nonconvulsive status epilepticus in a
      pregnant, epileptic woman is an unfortunate and unusual condition, which was
      simultaneously complicated by the presence of multiple etiological factors.

PMID- 16567328
TI  - "Burst and slow complexes" in nonconvulsive epileptic status.
AB  - Generalized 1Hz, burst-and-slow-wave complexes were observed in a comatosed
      patient with acute disseminated encephalomyelitis (ADEM) when she showed
      extremely intractable, generalized convulsions and fragmented myoclonus in the
      whole body. Two types of short-latency SEPs were obtained separately during the
      burst and slow phase of the EEG (SEP-burst and SEP-slow, respectively), which
      showed a two fold greater amplitude of N20 in the former than in the latter. This
      suggests enhanced responsiveness to the peripheral stimuli during the burst phase
      as compared with the slow phase. CSF and serum were positive for autoantibodies
      to NMDA receptors. The "burst and slow complexes" reported here are considered to
      be an atypical EEG pattern of a generalized epileptic phenomenon.

PMID- 16567329
TI  - Post-ictal forceful yawning in a patient with nondominant hemisphere epilepsy.
AB  - Yawning has been rarely described in association with seizures and not previously
      documented by video-EEG. We present a 48-year-old woman with a long history of
      non-dominant for speech hemisphere seizures and post-ictal yawning. Yawning was
      irresistible, forceful and often repetitive. We reviewed the few similar
      epileptic cases described in the literature and discussed the possible
      mechanisms. [Published with video sequences].

PMID- 16567330
TI  - Sleep-related laryngospasm: a video-polysomnographic recording.
AB  - We present a case of laryngospasm in a 12-year-old male who experienced sudden,
      nocturnal episodes of breathing difficulties and agitation. Apart from
      laryngospasm, the main differential diagnoses included frontal seizures, sleep
      related choking syndrome, sleep asthma, sleep apnoea and REM sleep behaviour
      disorder. The video and the EEG recordings supported the diagnosis of
      laryngospasm. The pH-metry confirmed the existence of reflux. Its treatment
      successfully controlled the episodes. This case illustrates, with a typical video
      recording, this infrequent type of paroxysmal event with an important
      differential diagnosis.[Published with video sequences].

PMID- 16567331
TI  - Uncommon, exceptional and atypical: a case of frontal lobe epilepsy due to
      cortical dysplasia.
AB  - We report a case of frontal lobe epilepsy due to focal cortical dysplasia that
      included three independent unusual features. The patient, a 45-year-old, right
      handed woman, had her first seizure at age 29, well into adulthood. Seizures had
      been easily controlled with medication for 15 years, then without provocation
      they became medically intractable during a single, identifiable day. Resection of
      the dysplastic tissue in the posterior dorsolateral right frontal cortex rendered
      the patient seizure-free, but produced a significant, non-fluent, Broca type,
      crossed aphasia. In addition, the seizure semiology was striking and remarkable,
      a common finding in frontal lobe epilepsy. [Published with video sequences].

PMID- 16567332
TI  - Myoclonus relieved by carbamazepine in subacute sclerosing panencephalitis.
AB  - A 20-year-old woman with subacute sclerosing panencephalitis, bedridden because
      of dystonic posturing and very frequent myoclonic involuntary movements, improved
      dramatically with carbamazepine. The favorable effect of the carbamazepine on
      myoclonus was demonstrated by discontinuing and reintroducing carbamazepine, and
      videoing the consequent reappearance and disappearance of the myoclonus.
      [Published with video sequences].

PMID- 16567333
TI  - Are epilepsy classifications based on epileptic syndromes and seizure types
      outdated?

PMID- 16567334
TI  - Gender equality and women's absolute status: a test of the feminist models of
      rape.
AB  - Feminist theory predicts both a positive and negative relationship between gender
      equality and rape rates. Although liberal and radical feminist theory predicts
      that gender equality should ameliorate rape victimization, radical feminist
      theorists have argued that gender equality may increase rape in the form of male
      backlash. Alternatively, Marxist criminologists focus on women's absolute
      socioeconomic status rather than gender equality as a predictor of rape rates,
      whereas socialist feminists combine both radical and Marxist perspectives. This
      study uses factor analysis to overcome multicollinearity limitations of past
      studies while exploring the relationship between women's absolute and relative
      socioeconomic status on rape rates in major U.S. cities using 2000 census data.
      The findings indicate support for both the Marxist and radical feminist
      explanations of rape but no support for the ameliorative hypothesis. These
      findings support a more inclusive socialist feminist theory that takes both
      Marxist and radical feminist hypotheses into account.

PMID- 16567335
TI  - Coping and violence exposure as predictors of psychological functioning in
      domestic violence survivors.
AB  - This study examines the differential effects of adult and childhood physical and
      psychological abuse, abuse-specific coping, and psychological adjustment in
      battered women seeking emergency shelter. Multivariate regression analyses
      confirmed the devastating impact of psychological abuse (childhood and
      concurrent) on battered women's adjustment. The results corroborated prior
      research suggesting a cumulative vulnerability to psychological victimization in
      a substantial proportion of residents. Unexpectedly, frequency of physical
      violence was unrelated to women's distress. The study argues that modes of coping
      traditionally considered adaptive (e.g., engaged, proactive) may be unsafe for
      battered women and children. The multifaceted nature of survivors' coping choices
      is discussed.

PMID- 16567336
TI  - Arresting developments: trends in female arrests for domestic violence and
      proposed explanations.
AB  - This article represents an effort to generate more systematic and specified
      discussion on the topic of unintended consequences in the movement to decrease
      violence against women. In this case, the consequence is increases in female
      arrests for domestic violence. This article builds on recent discussions by first
      using a sample of data to examine felony domestic violence arrest rates for men
      and women. The data support the conclusion that domestic violence arrests of
      women have increased. Second, the article presents six explanations that are
      derived from existing literature. Although the authors do not offer empirical
      tests of these explanations, this presentation can play an important part in
      better understanding the outcomes of criminal justice policies that are aimed at
      increasing victim safety.

PMID- 16567337
TI  - Electroshock as a form of violence against women.
AB  - This article reframes electroconvulsive therapy as a form of violence against
      women. Drawing on women's testimony and on scientific research, it establishes
      that this "treatment," which is overwhelmingly given to women, results in
      extensive cognitive and physical impairment. Correspondingly, it functions and is
      experienced as a form of assault and social control, not unlike wife battery.
      Emergent themes include electroshock as life destroying, a sign of contempt for
      women, punishment, a means of enforcing sex roles, a way to silence women about
      other abuse, an assault, traumatizing for those who undergo it and those forced
      to witness it.

PMID- 16567339
TI  - Hand-assisted retroperitoneoscopic living donor nephrectomy: first UK experience.

PMID- 16567340
TI  - Persistent T-cell activation and clinical correlations in patients with ANCA
      associated systemic vasculitis.
AB  - BACKGROUND: Although in antineutrophil cytoplasmic autoantibodies (ANCA)
      associated systemic vasculitis (AASV) patients, activation of T-cells has been
      described, persistence of these alterations has not been well characterized. This
      study was conducted to define persistent T-cell activation (PTA) in AASV patients
      and to assess whether this correlates with disease activity, disease severity,
      age or therapy. METHODS: The expression of CD4, CD45RO, CD25, CD26, CD28, CCR7
      and HLA-DR was examined longitudinally in 38 consecutive AASV patients. Clinical
      parameters were compared by univariate and multiple analysis and Kaplan-Meier
      curves for relapse-free survival were calculated. RESULTS: PTA could be defined
      as either of two activation phenotypes, i.e. a low percentage of CD4+ CD45RO- T
      cells or a high percentage of CD25 in the naive CD4+ population (n = 26), since
      only these phenotypes were stable over time and were not associated with active
      disease. In patients with PTA, major organ involvement was significantly more
      often found than in patients without PTA. Moreover, the cumulative
      cyclophosphamide dose (26.86 vs 8.53 P < 0.01) was significantly increased in
      these patients, suggesting that PTA was associated with disease severity. In
      general, patients with PTA were older than those without (62.92 +/- 9.4 years vs
      48.42 +/- 16.9 years respectively, P < 0.01). PTA was independent of disease
      duration. Interestingly, patients with a low percentage of CD4+CD45RO- T-cells
      were significantly more often diagnosed as microscopic polyangiitis (P < 0.01).
      CONCLUSION: We identified two independent phenotypes of T-cell activation in AASV
      patients. These phenotypes are persistent and do not reflect disease activity.
      PTA predominantly occurs in patients with severe disease. This might explain the
      higher cumulative cyclophosphamide dose found in these patients.

PMID- 16567341
TI  - Relation of haemofilter type to venous catheter resistance is crucial for
      filtration performance and haemocompatibility in CVVH--an in vitro study.
AB  - BACKGROUND: Main factors for the overall performance of haemofilters (HF) are
      membrane features and filter durability without clogging/clotting of capillaries.
      However, the venous line resistance (Pv) is a powerful force for net filtrate
      flux resulting in haemoconcentration and thus is enhancing the phenomenon of
      membrane clogging. Therefore, we hypothesized that catheter type, as it is
      associated with Pv-levels, contributes to the extent in which filter longevity
      and filtration performance are restricted due to blocked hollow fibres. METHODS:
      Heparinized porcine blood (5 IU/ml) was circulated in an in vitro system for
      haemofiltration (FH6S-filters were used, Ca. Gambro). Three different sizes of
      catheters for peripheral vein access (Vygonuele V, Ca. Vygon) were alternately
      inserted into the circuit for blood return from the filter to the reservoir. To
      produce Pv-levels lower than commonly induced by Shaldon catheters, a 14G
      vygonuele was used. Pv-levels standard for 11-12 French catheters were provided
      by using a 16G-vygonuele. To produce Pv-levels common for low-French or tri-lumen
      catheters, a shortened 18G-vygonuele was used. The respective Pv-levels attained
      were compared with respect to the overall filtration performance (system
      pressures, haemocompatibility and sieving coefficients). RESULTS: Catheters of 14
      and 16G enabled transiently maximal blood flow (Qb)/filtration rates (Qf) of
      300/60 ml/min and continuous filtration with Qb/Qf of 200/40 ml/min. The
      shortened 18G catheter reduced maximal flow rates down to Qb/Qf of 200/40 ml/min,
      and continuous flow rates down to Qb/Qf of 125/25 ml/min. At the end, median
      values for blocked hollow fibres were, 35% in the 14G-group, 40% in the 18G-group
      and 70% in the 16G-group. Haemocompatibility appeared to be higher in the 14G
      group with respect to various parameters when compared with the other groups.
      CONCLUSIONS: The flow resistance by the catheter chosen for haemofiltration
      clearly influenced the filtration performance. Thus, investigations focused on
      compatibility of catheter type as it related to Pv-levels with the particular
      method of renal replacement therapy that should be performed. This point could be
      crucial in reducing filter clogging and haemostasis during CVVH.

PMID- 16567342
TI  - Health impacts of macroeconomic crises and policies: determinants of variation in
      childhood malnutrition trends in Cameroon.
AB  - BACKGROUND: It is generally hypothesized that macro economic shocks worsen child
      health by lowering household economic status and limiting access to health care,
      but this proposition seldom has been tested empirically. We examined the effects
      of economic crises and adjustment programmes during the 1990s in Cameroon on
      childhood malnutrition in population subgroups and evaluated the household and
      health system mediators of these effects. METHODS: We used pooled cross-sectional
      data from two Demographic and Health Surveys conducted in 1991 and 1998. In
      multivariate analysis, we stratified data on child sex and age, maternal
      education, and place and region of residence. We used a linear regression model
      to estimate the net effects of changes in average household economic status and
      maternal health seeking behaviour (MHSB) on changes in the prevalence of
      malnutrition for each stratum, adjusting for all other variables. RESULTS: The
      prevalence of malnutrition in children younger than 3 years increased from 16 to
      23% (P < 0.001) between 1991 and 1998. The increase in urban areas, from 13 to
      15% (P = 0.391), mostly occurred in children of low-educated mothers. The
      increase in rural areas, from 19 to 25% (P < 0.001), mostly occurred in boys,
      children older than 6 months of age, those born to low-educated mothers, and
      those of low economic status. In urban areas, the advantage associated with
      higher maternal education was robust to all controls, and declines in economic
      status and MHSB were the mediators of increasing malnutrition. In rural areas,
      increase in malnutrition was higher in children with lower baseline economic
      status; decline in MHSB was a significant mediator of worsening nutritional
      status. CONCLUSIONS: The negative nutritional effects during economic crises and
      adjustment programmes of the 1990s in Cameroon were largest among children of low
      socioeconomic status. Declines in household economic status and access to health
      care were the mediators of increasing malnutrition.

PMID- 16567343
TI  - Propofol-alfentanil vs propofol-remifentanil for posterior spinal fusion
      including wake-up test.
AB  - BACKGROUND: Wake-up test can be used during posterior spinal fusion (PSF) to
      ensure that spinal function remains intact. This study aims at assessing the
      characteristics of the wake-up test during propofol-alfentanil (PA) vs propofol
      remifentanil (PR) infusions for PSF surgery. METHODS: Sixty patients with
      scoliosis and candidates for PSF surgery were randomly allocated in either
      alfentanil (PA) or remifentanil (PR) group. After an i.v. bolus of alfentanil 30
      microg kg(-1) in the PA group or remifentanil 1 microg kg(-1) in the PR group,
      anaesthesia was induced with thiopental and atracurium. During maintenance,
      opioid infusion consisted of alfentanil 1 microg kg(-1) min(-1) or remifentanil
      0.2 microg kg(-1) min(-1), in the PA group and the PR group, respectively. All
      patients received propofol 50 microg kg(-1) min(-1). Atracurium was given to
      maintain the required surgical relaxation. At the surgeon's request, all
      infusions were discontinued. Patients were asked to move their hands and feet.
      Time from anaesthetic discontinuation to spontaneous ventilation (T(1)), and from
      then until movement of the hands and feet (T(2)), and its quality were recorded.
      RESULTS: The average T(1) and T(2) were significantly shorter in the PR group
      [3.6 (2.5) and 4.1 (2) min] than the PA group [6.1 (4) and 7.5 (4.5) min].
      Quality of wake-up test, however, did not show significant difference between the
      two groups studied. CONCLUSION: Wake-up test can be conducted faster with
      remifentanil compared with alfentanil infusion during PSF surgery.

PMID- 16567344
TI  - Attenuation in invasive blood pressure measurement systems.
AB  - Poor fidelity invasive arterial blood pressure (IABP) traces are a frequent
      practical problem. It is common practice to describe any such trace as being
      'damped'; the resonance behaviour of IABP measurement systems having been
      extensively described in the literature. However, as poor quality arterial blood
      pressure signals are seen even with optimal pressure transduction circuits, this
      cannot be the sole mechanism. In this commentary the classical lumped-parameter
      Windkessel model is extended by postulating an additional impedance proximal to
      the site of IABP measurement. This impedance represents any mechanical
      obstruction to laminar flow. Equations are presented relating measured and actual
      arterial blood pressures in terms of the model impedances. The reactive
      properties of such a partial obstruction may lead to an IABP trace that is
      superficially similar in appearance to the case of an over-damped measurement
      system. However, this phenomenon should be termed 'attenuation' rather than
      'damping' and is probably more common. The distinction is of practical importance
      as the behaviour of the measured systolic and diastolic pressures is different --
      both are systematically underestimated and the mean arterial pressure is thus not
      preserved. Furthermore, this error varies inversely with the peripheral vascular
      resistance of the tissues distal to the measurement point, therefore apparently
      magnifying the effect of vasodilatation on blood pressure or derived quantities.

PMID- 16567345
TI  - Landiolol, an ultra-short-acting beta 1-adrenoceptor antagonist, does not alter
      the electroencephalographic effect of isoflurane in swine model.
AB  - BACKGROUND: beta-Adrenergic blocking agents may interact with anaesthetics, and
      several studies suggest that beta-blockers attenuate electroencephalographic
      responses during general anaesthesia. We have investigated the influence of
      landiolol, an ultra-short-acting beta 1-adrenoceptor antagonist, on the
      electroencephalographic effect of isoflurane in pigs. METHODS: Ten swine were
      anaesthetized through inhalation of 2% isoflurane. The inhalational concentration
      was then decreased to 0.5% and maintained for 25 min, before being returned to 2%
      and maintained for a further 25 min (control period). After control measurements,
      infusion of landiolol (at 0.125 mg kg(-1) min(-1) for 1 min, and then at 0.04 mg
      kg(-1) min(-1)) was started. After a 20 min stabilization period, the
      inhalational concentration was varied as in the control period (40 gamma
      landiolol). Finally, infusion of landiolol was increased from 0.04 to 0.2 mg kg(
      1) min(-1), and after a 20 min stabilization period, the inhalational
      concentration was again varied as in the control period (200 gamma landiolol).
      End-tidal isoflurane concentrations and spectral edge frequencies were recorded
      throughout the study. Analysis of the pharmacodynamics was performed using a
      sigmoidal inhibitory maximal effect model for spectral edge frequency vs effect
      site concentration. RESULTS: There were no significant differences in the effect
      of isoflurane among the conditions used. Landiolol did not shift the
      concentration-effect relationship [the effect-site concentration that produced
      50% of the maximal effect was 1.35 (0.17)% under control conditions, 1.30 (0.12)%
      at 40 gamma landiolol, and 1.38 (0.30)% at 200 gamma landiolol]. CONCLUSION:
      Landiolol does not alter the electroencephalographic effect of isoflurane.

PMID- 16567346
TI  - Non-technical skills in the intensive care unit.
AB  - In high-risk industries such as aviation, the skills not related directly to
      technical expertise, but crucial for maintaining safety (e.g. teamwork), have
      been categorized as non-technical skills. Recently, research in anaesthesia has
      identified and developed a taxonomy of the non-technical skills requisite for
      safety in the operating theatre. Although many of the principles related to
      performance and safety within anaesthesia are relevant to the intensive care unit
      (ICU), relatively little research has been done to identify the non-technical
      skills required for safe practice within the ICU. This review focused upon
      critical incident studies in the ICU, in order to examine whether the
      contributory factors identified as underlying the critical incidents, were
      associated with the skill categories (e.g. task management, teamwork, situation
      awareness and decision making) outlined in the Anaesthetists' Non-technical
      Skills (ANTS) taxonomy. We found that a large proportion of the contributory
      factors underlying critical incidents could be attributed to a non-technical
      skill category outlined in the ANTS taxonomy. This is informative both for future
      critical incident reporting, and also as an indication that the ANTS taxonomy may
      provide a good starting point for the development of a non-technical skills
      taxonomy for intensive care. However, the ICU presents a range of unique
      challenges to practitioners working within it. It is therefore necessary to
      conduct further non-technical skills research, using human factors techniques
      such as root-cause analyses, observation of behaviour, attitudinal surveys,
      studies of cognition, and structured interviews to develop a better understanding
      of the non-technical skills important for safety within the ICU. Examples of such
      research highlight the utility of these techniques.

PMID- 16567347
TI  - GnRH antagonists in ovarian stimulation for IVF.
AB  - The present review describes, on the basis of the currently available evidence,
      the consensus reached by a group of experts on the use of gonadotropin-releasing
      hormone (GnRH) antagonists in ovarian stimulation for IVF. The single or multiple
      low-dose administration of GnRH antagonist during the late-follicular phase
      effectively prevents a premature rise in serum luteinizing hormone (LH) levels in
      most women. Although controversy remains, most comparative studies suggest a
      slight, not significant reduction in the probability of pregnancy after IVF using
      GnRH antagonist versus GnRH agonist co-treatment. Published meta-analyses suggest
      that this slight difference in pregnancy rates is not attributed to chance.
      Further studies applying varying treatment regimens and outcome measures are
      required. Data are not in favour of a need to modify the starting dose of
      gonadotropins. Data are not in favour of increasing gonadotropin dose at GnRH
      antagonist initiation. The addition of LH from the initiation of ovarian
      stimulation or from GnRH antagonist administration does not appear to be
      necessary. Replacement of human chorionic gonadotropin (HCG) by GnRH agonist for
      triggering final oocyte maturation is associated with a lower probability of
      pregnancy. The optimal timing for HCG administration needs to be explored
      further. GnRH antagonist initiation on day 6 of stimulation appears to be
      superior to flexible initiation by a follicle of 14-16 mm, although earlier GnRH
      antagonist administration is worth further evaluation. Luteal phase
      supplementation in GnRH antagonist protocols remains mandatory in IVF. Effects of
      GnRH antagonist co-treatment on the incidence of ovarian hyperstimulation
      syndrome remains uncertain, although a trend is present in favour of the GnRH
      antagonists. The role of GnRH antagonists in ovarian stimulation for IVF appears
      to be promising, although many questions regarding preferred dose regimens and
      effects on clinical outcomes remain.

PMID- 16567348
TI  - No evidence of chromosome damage in chronic obstructive pulmonary disease (COPD).
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and
      mortality in industrialized countries. It is characterized by a progressive
      airflow limitation resulting from an abnormal inflammatory response of the lungs
      to inhaled gases and particles. Since oxidative stress is thought to play a role
      in COPD, and since increased oxidative stress is associated with chromosomal
      instability in several diseases, we investigated whether such relationship also
      exists in COPD. Whole blood lymphocytes from 49 COPD patients and 48 age- and sex
      matched controls were cultivated in vitro and cytogenetic damage was evaluated by
      micronucleus (MN) and sister-chromatid-exchange (SCE) assays. In patients with
      COPD, MN frequency was not significantly different from that of controls.
      Similarly, SCE frequency did not differ in the two groups suggesting no
      disturbance in DNA replication. Unlike other diseases characterized by oxidative
      stress, COPD does not appear to be associated with DNA damage.

PMID- 16567349
TI  - Relationship between genotoxicity biomarkers in somatic and germ cells: findings
      from a biomonitoring study.
AB  - A biomonitoring study to evaluate chromosome and DNA damage respectively in
      somatic and germ cells of a group of male workers exposed to styrene by using
      biomarkers of genotoxicity was carried out. Styrene-exposed workers from three
      different areas of Tuscany and healthy subjects, of comparable mean age, sex and
      lifestyle characteristics, as a control group not exposed to chemicals, have been
      enrolled. In addition to previous reports [L. Migliore, A. Naccarati, A. Zanello,
      R. Scarpato, L. Bramanti and M. Mariani (2002) Hum. Reprod., 17, 2912-2918; L.
      Migliore, A. Naccarati, F. Coppede et al. (2006) Pharmacogenet. Genomics, 16, 87
      99] we present now data on a cross-sectional investigation involving a
      homogeneous group of subjects for which data on both somatic and germ cells have
      been obtained from individuals (42 exposed and 25 controls). Somatic cell
      genotoxicity was assessed by analysing the frequency of micronucleated
      binucleated cells (MNBN) in blood lymphocytes. The micronucleus assay was coupled
      with centromeric fluorescence in situ hybridization (FISH) analysis. Primary DNA
      damage in germ cells was evaluated by alkaline single-cell gel electrophoresis
      (Comet assay) and the percentage of the tail DNA (%TD) was used as parameter of
      Comet evaluation. Moreover, to investigate the frequencies of aneuploidy and
      diploidy in sperm, we performed multicolour FISH, using DNA probes specific for
      the centromeric regions of sex chromosomes and chromosome 2, in decondensed sperm
      nuclei of samples with normal semen parameters in a subgroup of individuals.
      Mandelic and phenylglyoxylic acids (MAPGA) in end of shift samples were
      determined as biomarkers of internal dose. MAPGA excretion was consistent with an
      exposure to styrene above the threshold limit value-time weighted average
      concentration of 20 p.p.m. Styrene workers showed significantly higher frequency
      of MNBN as compared to controls (13.8 +/- 5.2 versus 6.2 +/- 5.1; P < 0.001), due
      to higher proportions of both micronuclei (MN) arising from chromosomal breakage
      (C-MN) and harbouring whole chromosomes (C+MN). DNA damage in sperm cells was
      also higher among styrene-exposed, the %TD being 11.02 +/- 2.99 versus 7.42 +/-
      2.30 in controls (P < 0.001). The incidence of aneuploidy and diploidy for the
      tested chromosomes in sperm did not show a statistically significant difference
      between workers and controls. However, a positive correlation was found between
      genotoxic damage detected in somatic and in germ cells, even after removing the
      effect of age (r = 0.475; P < 0.001). Although cytogenetic biomarkers detected
      both in somatic and germ cells were interrelated, no relationships were apparent
      with exposure parameters. Styrene exposure may increase the likelihood of both
      chromosome and DNA damage in somatic and germ cells, thus supporting the
      hypothesis of an interference on reproductive capacity among exposed workers.
      This is the first time that a field study shows a correlation between two
      biomarkers of genotoxicity evaluated at the same time in somatic and germ cells.

PMID- 16567352
TI  - Red flags need more evaluation.

PMID- 16567350
TI  - Evidence for genotoxicity of pesticides in pesticide applicators: a review.
AB  - A systematic review of the literature has been conducted and studies reporting
      investigations of genotoxicity biomarkers in pesticide workers have been assessed
      with view to establishing whether there was evidence for any risk to those using
      pesticides approved in the United Kingdom. Each of the studies was evaluated
      using a set of criteria drawn up by members of the UK Committee of Mutagenicity
      based upon the guidelines proposed by the International Programme on Chemical
      Safety (IPCS) working group [R. J. Albertini, D. Anderson, G. R. Douglas, L.
      Hagmar, K. Hemminki, F. Merlo, A. T. Natarajan, H. Norppa, D. E. Shuker, R. Tice,
      M. D. Waters and A. Aitio (2000) Mutat. Res., 463, 111-172]; 24 out of 70 studies
      met the criteria for inclusion in the substantive evaluation. Positive findings
      were compared with occupational practices and evidence of exposure to specific
      pesticides with view to developing hypotheses for further consideration.
      Seventeen of the 24 studies reported positive findings, although in the majority
      of these the magnitude of increase was small. There was some limited evidence
      that the use of benzimidazoles was more consistently associated with positive
      findings. However, limitations in the data, particularly evidence of exposure,
      did not allow definitive conclusions to be drawn. Also, it was noted that the use
      (or not) of personal protective equipment (PPE) was not well documented and in
      the few studies in which its use was reported, the findings were more likely to
      be positive in the absence of PPE usage. An independent epidemiological review
      concluded that all studies were of limited design, particularly with regards to
      study size, the assessment of subject selection and potential recruitment bias.
      Variance in genotoxicity indices in the control population and a lack of
      understanding of the factors influencing this variability complicate attempts to
      characterize positive responses. More substantive data are needed in this respect
      so that the significance of relatively small increases in biomonitoring indices
      can be accurately assessed. Once these data are available, a study in workers
      using benzimidazoles would be appropriate.

PMID- 16567353
TI  - Thrombocytopaenia in lupus as a marker of adverse outcome--seeking Ariadne's
      thread.
AB  - OBJECTIVE: To assess the role of thrombocytopaenia as an independent predictor of
      outcome in patients with systemic lupus erythematosus (SLE). METHODS: This was a
      single-centre, retrospective, matched case-control study (1:2). Fifty consecutive
      Greek SLE patients were selected at random who had developed thrombocytopaenia
      during the disease course (cases) were compared with 100 SLE patients with no
      history of thrombocytopaenia, and matched for age, sex and disease duration
      (controls). Overall damage was assessed at the end of follow-up, using Systemic
      Lupus International Collaborating Clinics index. Total number of irreversible
      organ-damage events for both groups were recorded. Rates for specific outcomes
      and incidence-rate ratios (IRRs) for damage were estimated. Multivariate analysis
      estimating influential clinical and immunological factors for outcome, including
      thrombocytopaenia, was performed. RESULTS: After 583 person-years of follow-up
      for cases and 1155 for controls, we found that thrombocytopaenic individuals have
      a higher risk for damage (IRR 1.96, 1.52-2.53) compared with their matched
      controls and this effect persists throughout the course of their disease. They
      also have a predilection to certain types of damage involving heart and kidneys.
      Among other significant factors associated with damage in multivariate analysis
      (disease activity, serositis, anti-cardiolipin antibodies, central nervous system
      involvement), thrombocytopaenia appears as the most influential. CONCLUSION:
      Thrombocytopaenia is a quantitive and qualitative marker of impending damage in
      SLE patients.

PMID- 16567354
TI  - The Juvenile Dermatomyositis National Registry and Repository (UK and Ireland)-
      clinical characteristics of children recruited within the first 5 yr.
AB  - OBJECTIVES: To identify epidemiological, clinical and laboratory characteristics
      of juvenile dermatomyositis (JDM) in a national multi-centre cohort of patients,
      and to review recent changes in the understanding of management and prognosis in
      the light of these data. METHODS: All children with idiopathic inflammatory
      myositis recruited to the Juvenile Dermatomyositis National Registry and
      Repository (UK and Ireland) were included. Features at presentation, and later in
      disease, were assessed and evaluated. A total of 63 out of 175 children with a
      new diagnosis of myositis were recruited at the time of diagnosis and followed
      prospectively. Out of the 175 children, 122 diagnosed prior to 2000 were
      recruited retrospectively, with subsequent data collected prospectively. RESULTS:
      One patient died (0.7%), which is equivalent to one death per 465 patient years.
      Data were available at the time of analysis on 151 registered patients. The most
      common presenting features were characteristic rash, weakness, tiredness,
      Gottron's patches and myalgia. Muscle biopsy, magnetic resonance imaging and
      muscle enzymes were frequently, but not always, abnormal. Muscle enzymes and
      erythrocyte sedimentation rate were not useful markers of disease activity.
      CONCLUSIONS: The JDM National Registry and Repository captures data on a
      significant cohort of children with inflammatory myositis. The current study
      reports the largest European cohort of children with dermatomyositis to date.
      This powerful resource will help improve our understanding of this rare disease.
      Prospective data collection will allow a fuller analysis of poor prognostic
      features, impact of therapy, and variable outcome of childhood myositis.

PMID- 16567355
TI  - The ICF comprehensively covers the spectrum of health problems encountered by
      health professionals in patients with musculoskeletal conditions.
AB  - OBJECTIVES: The objective of this study was to investigate, whether the
      International Classification of Functioning, Disablity and Health (ICF)
      comprehensively covers the spectrum of health problems encountered by medical
      doctors and physiotherapists in patients with musculoskeletal conditions.
      METHODS: A worldwide e-mail survey with questionnaires that requested lists of
      relevant areas in the ICF components-body functions, body structures, activities
      and participation, and environmental factors-in patients with rheumatoid
      arthritis, osteoarthritis, low back pain and osteoporosis was conducted. The
      suitability of linking the named concepts to the ICF as well as the precision of
      the linking was characterized by assigning the concepts to six groups. RESULTS:
      All concepts that were named by the experts could be linked to the ICF, with the
      exception of personal factors. Between 32% (environmental factors) and 51%
      (activities and participation) of the named concepts were linked to an ICF
      category with an identical meaning and the same grade of precision. All other
      named concepts were linked to ICF categories with a lower level of precision, or
      encompassed more than one ICF category, or were linked to an ICF category with a
      related, but not identical meaning. CONCLUSIONS: The ICF covers comprehensively
      the spectrum of problems encountered in patients with musculoskeletal conditions
      by clinical experts throughout the world. This strengthens the validity of the
      ICF in the view of the users and will encourage the use of ICF-based applications
      such as the ICF checklist and the now-developed ICF Core Sets.

PMID- 16567356
TI  - Elevated serum levels of soluble receptor activator of nuclear factors-kappaB
      ligand (sRANKL) and reduced bone mineral density in patients with ankylosing
      spondylitis (AS).
AB  - OBJECTIVE: To assess bone mineral density (BMD), serum levels of soluble receptor
      activator of nuclear factors-kappaB ligand (sRANKL) and osteoprotegerin (OPG) in
      patients with ankylosing spondylitis (AS), and to determine their relationships
      with disease activities. METHODS: Serum levels of sRANKL and OPG in AS were
      measured by sandwich enzyme-linked immunosorbent assay. The disease activities
      were determined using Bath Ankylosing Spondylitis Disease Activity Score Index,
      Bath Ankylosing Spondylitis Functional Index , Bath Ankylosing Spondylitis
      Metrology Index and Bath Ankylosing Spondylitis Patient Global Score. BMD of
      femur and lumbar spine was measured by dual energy X-ray absorptiometry.
      Radiological grading was determined by New York criteria for sacroiliitis and
      modified Stoke Ankylosing Spondylitis Spine Score. RESULTS: Osteoporosis and
      osteopaenia of femoral neck were found in 33 and 41% of patients, respectively.
      BMD of femoral neck showed negative correlation with disease activity indexes,
      erythrocyte sedimentation rate and C-reactive protein. The serum sRANKL levels
      and the ratio of sRANKL to OPG were significantly higher in patients with AS than
      those of controls. The sRANKL/OPG ratio tended to increase in patients with
      reduced BMD and radiological findings of active inflammation. CONCLUSION: About
      74% of AS patients have reduced BMD and this change reflects disease activity.
      Serum sRANKL levels and sRANKL/OPG ratios are up-regulated in patients with AS
      and have relationship with BMD and radiological changes. These results suggest
      that the imbalance between RANKL and OPG might be involved in the pathogenesis
      and clinical courses of osteoporosis in AS.

PMID- 16567357
TI  - Improved health-related quality of life for rheumatoid arthritis patients treated
      with abatacept who have inadequate response to anti-TNF therapy in a double
      blind, placebo-controlled, multicentre randomized clinical trial.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) patients who have inadequate response to
      anti-tumour necrosis factor (TNF) therapy currently have treatment options that
      are limited and less than optimal in their risk-to-benefit ratio. Abatacept
      provides a new generation of RA medications that has previously been demonstrated
      to have positive clinical outcomes with this population. The current study sought
      to demonstrate the efficacy of abatacept on quality of life (QoL) for RA patients
      with inadequate response to anti-TNF therapy. METHODS: Patients were entered into
      a double-blind, placebo-controlled, multicentre randomized clinical trial, with
      258 patients randomized to abatacept + disease-modifying anti-rheumatic drugs
      (DMARDs) and 133 patients randomized to placebo + DMARDS. The QoL was measured
      with the Short Form Health Survey (SF-36), Health Assessment Questionnaire (HAQ)
      and fatigue visual analogue scale, and was analysed with basic (ANOVA, chi
      square) and multigroup growth curve techniques to assess differential change over
      time. RESULTS: Treatment group QoL improved significantly more than placebo on
      the HAQ and fatigue indices, as well as seven of the eight SF-36 scales and SF-36
      physical and mental summary scores. Improvement rate was faster for abatacept
      than for placebo on the QoL measures, and the improvements from abatacept related
      to normal levels of QoL on many domains. CONCLUSION: Clinically relevant benefits
      of abatacept over placebo are discussed regarding improving QoL. Importantly, the
      larger rate of change for abatacept over placebo provides clinicians with a
      medication that can lead to meaningful changes in a patient's life within a few
      weeks, even when the patient previously failed anti-TNF therapy.

PMID- 16567358
TI  - Synovial fibroblasts: key players in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that
      primarily affects the joints and ultimately leads to their destruction. The
      involvement of immune cells is a general hallmark of autoimmune-related
      disorders. In this regard, macrophages, T cells and their respective cytokines
      play a pivotal role in RA. However, the notion that RA is a primarily T-cell
      dependent disease has been strongly challenged during recent years. Rather, it
      has been understood that resident, fibroblast-like cells contribute significantly
      to the perpetuation of disease, and that they may even play a role in its
      initiation. These rheumatoid arthritis synovial fibroblasts (RASFs) constitute a
      quite unique cell type that distinguishes RA from other inflammatory conditions
      of the joints. A number of studies have demonstrated that RASFs show alterations
      in morphology and behaviour, including molecular changes in signalling cascades,
      apoptosis responses and in the expression of adhesion molecules as well as matrix
      degrading enzymes. These changes appear to reflect a stable activation of RASFs,
      which occurs independently of continuous exogenous stimulation. As a consequence,
      RASFs are no longer considered passive bystanders but active players in the
      complex intercellular network of RA.

PMID- 16567359
TI  - Lack of genetic association of the Toll-like receptor 4 (TLR4) Asp299Gly and
      Thr399Ile polymorphisms with spondylarthropathies in a Hungarian population.
AB  - OBJECTIVES: Bacteria have long been suggested as aetiological factors in the
      genetically susceptible host in spondylarthropathies, including ankylosing
      spondylitis (AS) and reactive arthritis (ReA). Variability of the Toll-like
      receptor 4 (TLR4) gene has been shown to play a role in the inflammatory response
      to certain bacterial infections. We investigated whether TLR4 Asp299Gly and
      Thr399Ile polymorphisms contribute to the genetic background of
      spondylarthropathies in a cohort of Hungarian patients with AS and ReA. METHODS:
      DNA was obtained from patients with AS (n=138), ReA (n=91) and ethnically matched
      healthy controls (n=140). Genotyping was carried out by polymerase chain reaction
      restriction fragment length polymorphism analysis and the results were confirmed
      by direct sequencing. RESULTS: No significant differences in allele or genotype
      frequencies were observed between controls and either the AS patients or the ReA
      patients. Clinical characteristics of these groups were unrelated to the presence
      of any of these polymorphisms. CONCLUSIONS: Toll-like receptor 4 Asp299Gly and
      Thr399Ile polymorphisms do not contribute to disease susceptibility in either AS
      or ReA. Functional abnormalities of the TLR4 signalling pathway suggested in
      spondylarthropathies seem not to be genetically determined by these two common
      polymorphisms.

PMID- 16567361
TI  - Studying the striving and opposing forces in newspaper journalism: the actantial
      model of health promotion.
AB  - The cultural aspects of health promotion are important in policy development as
      well as in assessing effectiveness of health promotion activities. The discourses
      on promoting health and well-being in journalism reflect the health promotion
      culture in society. This article illustrates how health promotion is portrayed by
      147 newspaper items from the two Finnish quality dailies during the period 2002
      2004 and introduces a semiotic Actantial Model of Health Promotion (AMHP) for
      studying health promotion cultures. The most popular news themes on health
      promotion were physical and social environment, welfare services, nutrition and
      obesity, and mental well-being. The actants (actors, actions and abstract factor)
      of health promotion were identified and the AMHP with seven key actants
      (generator, health-object, public, tool, executor, threat and obstacle) was
      constructed. The model sheds light on two sides of health promotion discourses in
      journalism. The dominant culture of health promotion was represented by policy
      actions, information, education and scientific research, which were defined by
      health experts, decision-makers and researchers. Representations of the opposite
      culture--'the otherness' of health promotion included external harmful factors
      and unhealthy behaviours, mentalities opposed to being health-oriented,
      rationally uncontrolled living, disorder, disharmony and insecurity. The opposing
      factors were presented by people and institutions lacking the will, ability or
      motivation for a health-oriented life. To understand better the values of health
      promotion, it is necessary to assess the characteristics of the opposite side of
      health promotion culture, because the current dominant values can be described
      more clearly by the boundaries--by 'otherness'. The study argues that the AMHP
      can be used as a semiotic method to identify the value dimensions and the
      boundaries between the dominant and the opposite discourses of health promotion
      in various communications such as advertising and health education. Also, it
      provides a tool for the analysis of the media's role in 'victimization' or
      'heroization' of various population groups.

PMID- 16567360
TI  - Development of a novel 2D proteomics approach for the identification of proteins
      secreted by primary chondrocytes after stimulation by IL-1 and oncostatin M.
AB  - OBJECTIVES: To develop a proteomics approach to study changes in the secreted
      protein levels of primary human chondrocytes after stimulation by the pro
      inflammatory cytokines interleukin-1 and oncostatin M. METHODS: Using both the
      primary human articular and bovine nasal chondrocyte-conditioned mediums, methods
      were investigated to enable the separation of proteins by two-dimensional (2D)
      gel electrophoresis. Differentially regulated proteins were identified using
      tandem electrospray mass spectrometery. RESULTS: We discovered that proteoglycans
      and glycosylaminoglycans (GAGs) secreted by chondrocytes significantly interfered
      with 2D gel focusing. Several different methods for GAG removal were attempted
      including enzymic digestion, cetyl pyridinium chloride precipitation and anion
      exchange in high salt. The anion exchange proved to be the most effective. Even
      from these initial gels, we were able to identify eight proteins produced by
      human chondrocytes: matrix metalloproteinase (MMP)-1, MMP-3, YKL40, cyclophilin
      A, beta2-microglobulin, transthyretin, S100A11, peroxidine 1 and cofilin. MMP-1,
      MMP-3, YKL40 and cyclophilin A were all identified as processed, smaller peptide
      fragments. CONCLUSIONS: We were able to develop a novel sample preparation
      protocol to allow the reproducible sample preparation of secreted proteins from
      human chondrocytes. From the initial data, we were able to show that at least
      some of the proteins produced were cleaved to smaller fragments as a result of
      proteolysis. Therefore, this technique provides valuable information about
      protein processing which gene-based arrays do not.

PMID- 16567362
TI  - Bayesian inference in a hidden stochastic two-compartment model for feline
      hematopoiesis.
AB  - In this paper, we describe a hidden two-compartment stochastic process used to
      model the kinetics of feline hematopoietic stem cells (HSCs) in continuous time.
      Because of the experimental design and data collection scheme, the inferential
      task presents numerous challenges. While the hematopoietic process evolves in
      continuous time, the observations are collected only at discrete irregular times
      and are a probabilistic function of the state of the process. In addition, the
      animals go through an experimental procedure such that their reserve of HSCs is
      severely depleted at the start of the observation period. This impedes any
      approximation of the hematopoietic process with a continuous state-space process
      (normal approximation of the transition probabilities would be inaccurate when
      the state of the process, i.e. the number of stem cells, is small). We implement
      a Markov chain Monte Carlo algorithm that allows us to estimate the posterior
      distribution of the parameters of the hematopoietic process while maintaining its
      state-space discrete (i.e. without using any approximation). We show the
      performance of the algorithm on simulated data. Finally, we apply the algorithm
      to data on multiple experimental cats and provide estimates of the rates of the
      fates of feline HSCs. The obtained estimates are in agreement with the estimates
      obtained with different methods published in the medical literature. However, the
      proposed approach makes a more efficient use of the data and hence the parameter
      estimates are much more accurate than the one obtained with the methods
      previously proposed.

PMID- 16567363
TI  - GBPM: GRID-based pharmacophore model: concept and application studies to protein
      protein recognition.
AB  - MOTIVATION: Automatic procedures to obtain pharmacophore models from
      experimentally determined macromolecular complexes can help in the drug discovery
      process, especially when protein-protein recognition plays an important
      biological role. RESULTS: The GRID-based pharmacophore model (GBPM) is a fully
      objective method for defining most relevant interaction areas in complexes
      deriving pharmacophore models from three-dimensional (3D) molecular structure
      information. It is based on logical and clustering operations with 3D maps
      computed by the GRID program on structurally known molecular complexes. In this
      manuscript we describe the concept and discuss application examples regarding
      protein-protein recognition. In particular two complexes selected in the Protein
      Data Bank have been tested to evaluate the GBPM capability to identify
      interaction areas. The results obtained show the capabilities of this new
      bioinformatic method.

PMID- 16567364
TI  - A dynamic programming algorithm for binning microbial community profiles.
AB  - MOTIVATION: A number of community profiling approaches have been widely used to
      study the microbial community composition and its variations in environmental
      ecology. Automated Ribosomal Intergenic Spacer Analysis (ARISA) is one such
      technique. ARISA has been used to study microbial communities using 16S-23S rRNA
      intergenic spacer length heterogeneity at different times and places. Owing to
      errors in sampling, random mutations in PCR amplification, and probably mostly
      variations in readings from the equipment used to analyze fragment sizes, the
      data read directly from the fragment analyzer should not be used for down stream
      statistical analysis. No optimal data preprocessing methods are available. A
      commonly used approach is to bin the reading lengths of the 16S-23S intergenic
      spacer. We have developed a dynamic programming algorithm based binning method
      for ARISA data analysis which minimizes the overall differences between
      replicates from the same sampling location and time. RESULTS: In a test example
      from an ocean time series sampling program, data preprocessing identified several
      outliers which upon re-examination were found to be because of systematic errors.
      Clustering analysis of the ARISA from different times based on the dynamic
      programming algorithm binned data revealed important features of the biodiversity
      of the microbial communities.

PMID- 16567365
TI  - Finding regions of significance in SELDI measurements for identifying protein
      biomarkers.
AB  - MOTIVATION: There is a well-recognized potential of protein expression profiling
      using the surface-enhanced laser desorption and ionization technology for
      discovering biomarkers that can be applied in clinical diagnosis, prognosis and
      therapy prediction. The pre-processing of the raw data, however, is still
      problematic. METHODS: We focus on the peak detection step, where the standard
      method is marked by poor specificity. Currently, scientists need to inspect
      individual spectra visually and laboriously in order to verify that spectral
      peaks identified by the standard method are real. Motivated by this multi
      spectral process, we investigate an analytical approach-called RS for 'regions of
      significance'-that reduces the data to a single spectrum of F-statistics
      capturing significant variability between spectra. To account for multiple
      testing, we use a false discovery rate criterion for identifying potentially
      interesting proteins. RESULTS: We show that RS has better operating
      characteristics than several existing methods and demonstrate routine
      applications on a number of large datasets.

PMID- 16567366
TI  - Identification and characterization of oviductal glycoprotein-binding protein
      partner on gametes: epitopic similarity to non-muscle myosin IIA, MYH 9.
AB  - The mammalian estrogen induced oviductal glycoprotein (OGP) has been known to
      associate with capacitated sperm, oocytes and developing embryos. This study
      aimed to identify the putative binding partner of OGP on gametes using N-terminal
      peptide of bonnet monkey (Macaca radiata) OGP, Nmon, as bait. A protein(s) of
      molecular size approximately 54 kDa was detected by far-western blot analysis of
      detergent solubilized human sperm proteins. MALDI-TOF mass spectra analysis of
      approximately 54 kDa tryptic peptides gave a significant hit to non-muscle myosin
      heavy chain. Biochemical characterization of approximately 54 kDa was done with
      antibodies specific to non-muscle myosin IIA, MYH9. The approximately 54 kDa
      protein, possible breakdown product of MYH9, immunoreacted with MYH9 antibody in
      western blot analysis. OGP binding to approximately 54 kDa could also be
      demonstrated in far-western blot analysis of detergent solubilized human sperm
      proteins and nuclear matrix intermediate filament (NM-IF) preparations from human
      sperm and mouse oocytes. Far-western blot analysis of MYH9 enriched by
      immunoprecipitation identified the native approximately 220 kDa protein as OGP
      binding partner. The identical and characteristic immunogold localization pattern
      of Nmon and MYH9 on sperm NM-IF preparation substantiated these findings. The
      results suggest that OGP binds to both gametes through its interaction with MYH9
      through the non-glycosylated N-terminal conserved region of OGP, spanning the
      residues 11-137.

PMID- 16567367
TI  - Histamine uptake by human endometrial cells expressing the organic cation
      transporter EMT and the vesicular monoamine transporter-2.
AB  - Cellular reuptake of monoamines, which is mediated by cell membrane transporters,
      is followed by accumulation in vesicles by vesicular monoamine transporters
      (VMAT). The aim of this study was to demonstrate the presence of functional
      monoamine transporters with high affinity for histamine in human endometrial
      tissue, since histamine has been implicated as a paracrine signal during
      endometrial decidualization and embryo implantation. In situ hybridization with
      (35)S-labelled cRNA probes was used for detection of the organic cationic
      transporter-2 (OCT-2), the extraneuronal monoamine transporter (EMT), and VMAT-2
      in cryosections of normal human endometrial tissue. To identify functional
      transporters for histamine in endometrial cells, we incubated primary cultures of
      stromal cells and cultures of attached glands with (3)H-labelled histamine.
      Cultures were pretreated with either corticosterone, a specific inhibitor of EMT,
      or reserpine, a specific inhibitor of VMAT-2. EMT mRNA was localized in the
      stroma with peak expression in the secretory phase, whereas OCT-2 mRNA was
      expressed by few cells in the stroma throughout the cycle. VMAT-2 mRNA was
      localized in the stroma during the proliferative phase and in the epithelium
      during the secretory phase. Thus, EMT and VMAT-2, which both have high affinity
      for histamine, are strongly expressed in endometrial cells. Both corticosterone
      and reserpine significantly reduced the uptake of (3)H-histamine in stromal cells
      during the proliferative as well as the secretory phase. This indicates the
      presence of functional EMT and VMAT-2 transporter proteins throughout the cycle,
      even though their periods of maximal mRNA expression were limited. The results of
      uptake experiments with glandular epithelial cells confirmed not only the
      presence of functional VMAT-2 transporter protein in the secretory phase but also
      the absence of a histamine-specific plasma membrane transporter throughout the
      cycle. Thus, endometrial tissue contains both plasma membrane and vesicular
      membrane monoamine transporters with high affinity for histamine. They can
      potentially influence the reproductive process by the uptake of extracellular
      histamine and subsequent release on demand.

PMID- 16567368
TI  - Structural basis of carbohydrate recognition by a Man(alpha1-2)Man-specific
      lectin from Bowringia milbraedii.
AB  - The crystal structure of the seed lectin from the tropical legume Bowringia
      milbraedii was determined in complex with the disaccharide ligand Man(alpha1
      2)Man. In solution, the protein exhibits a dynamic dimer-tetramer equilibrium,
      consistent with the concanavalin A-type tetramer observed in the crystal.
      Contacts between the tetramers are mediated almost exclusively through the
      carbohydrate ligand, resulting in a crystal lattice virtually identical to that
      of the concanavalin-A:Man(alpha1-2)Man complex, even though both proteins have
      less than 50% sequence identity. The disaccharide binds exclusively in a
      "downstream" binding mode, with the non-reducing mannose occupying the
      monosaccharide-binding site. The reducing mannose is bound in a predominantly
      polar subsite involving Tyr131, Gln218, and Tyr219.

PMID- 16567369
TI  - Effects of caloric restriction and exercise on age-related, chronic inflammation
      assessed by C-reactive protein and interleukin-6.
AB  - Chronic inflammation is associated with the aging process and numerous age
      related pathologies. We evaluated the effects of age, caloric restriction (CR),
      and exercise on plasma C-reactive protein (CRP), interleukin-6, and total
      antioxidant capacity in Fisher 344 rats. The inflammatory markers were analyzed
      using enzyme-linked immunosorbent assays (ELISA), while total antioxidant
      potential was determined by a spectrophotometric method. An increase in
      circulating levels of CRP with age was attenuated with long-term 40% CR; short
      term 40% CR in young animals also reduced CRP concentration compared to age
      matched controls. Lifelong exercise with 8% CR showed a marked decrease in CRP
      levels compared to 8% CR controls and an even greater reduction compared to ad
      libitum-fed rats. Plasma interleukin-6 levels remained unchanged with age, CR,
      and exercise, whereas inflammation levels showed an inverse association with
      plasma antioxidant status. These studies highlight the anti-inflammatory effects
      of CR and exercise.

PMID- 16567370
TI  - Gene expression and physiologic responses of the heart to the initiation and
      withdrawal of caloric restriction.
AB  - Aging increases and caloric restriction (CR) decreases morbidity and mortality
      associated with the cardiovascular system. Using Affymetrix microarrays, we
      identified changes in heart gene expression induced by aging and CR in male mice.
      Eight weeks of CR (CR8) reproduced 19% of the long-term CR (LTCR)-related
      expression changes. Because CR8 begins to extend the life span of these mice,
      these genes may be keys to its cardioprotective effects. CR8 and LTCR changed
      gene expression in a manner consistent with reduced remodeling and fibrosis, and
      enhanced contractility and energy production via lipid beta-oxidation. Molecular
      and histochemical studies indicated that CR reduced natriuretic peptide precursor
      type B and collagen expression, and reduced perivascular collagen deposition. We
      found smaller cardiomyocytes in the left ventricle of old-LTCR mice, suggesting
      reduced age-related cell death. Eight weeks of control feeding returned 97% of
      the LTCR-responsive genes to control expression levels. Thus, key CR-induced
      effects are rapidly responsive to diet, suggesting reduced caloric intake has
      rapid, positive effects on the heart.

PMID- 16567371
TI  - Upregulation of aortic adhesion molecules during aging.
AB  - To investigate effects of aging on adhesion molecules (AMs), the present study
      assessed the expressions of aortic P-selectin and vascular adhesion molecule-1
      (VCAM-1) in young (6-month-old) and old (24-month-old) Fischer 344 rats fed ad
      libitum (AL) or calorie-restricted diets. Results showed increased levels of
      aortic P-selectin and VCAM-1 in the old AL rats, causing excessive leukocyte
      infiltration as indicated by enhanced myeloperoxidase level. These elevations
      were parallel to increased oxidative stress including lipid peroxides during
      aging. Then involvement of redox-sensitive transcription factor nuclear factor
      kappaB was analyzed, and greater activation of nuclear factor-kappaB-inducing
      kinase (NIK)/IkappaB kinase (IKK)/Inhibitor of kappaB (IkappaB) pathway in aorta
      from old AL rats was found. Further, in cultured endothelial cells challenged by
      various oxidative stimuli, the induced redox imbalance triggered overexpression
      and promoter activities of P-selectin and VCAM-1. Our study documented that
      aortic upregulated AMs with age are closely related to activation of
      NIK/IKK/IkappaB/nuclear factor-kappaB pathway brought on by oxidative stress.

PMID- 16567372
TI  - Molecular regulation of apoptosis in fast plantaris muscles of aged rats.
AB  - This study tested the hypothesis that aging exacerbates apoptotic signaling in
      rat fast plantaris muscle during muscle unloading. Plantaris muscle mass was 22%
      lower in aged animals and the apoptotic index was 600% higher, when compared to
      those in young adult animals. Following 14 days of hind-limb unloading, absolute
      plantaris muscle mass was 20% lower in young adult animals with a corresponding
      200% higher elevation of the apoptotic index. Unloading had no affect on muscle
      weight or apoptotic index of aged plantaris muscles. The changes in pro-apoptotic
      messenger RNA (mRNA) for apoptotic protease activating factor-1 (Apaf-1), Bax,
      and inhibitor of differentiation protein-2 (Id2) were exacerbated with aging. Bax
      and Bcl-2 protein levels were also altered differently in aged muscle, compared
      to young. Significant positive correlations were observed between the changes in
      Id2 and Bax mRNA, and Id2 and caspase-9 mRNA. These data suggest that a pro
      apoptotic environment may contribute to aging-associated atrophy in fast skeletal
      muscle, but apoptotic signaling differs by age.

PMID- 16567374
TI  - Frailty and the foolishness of Eos.

PMID- 16567375
TI  - Phenotype of frailty: characterization in the women's health and aging studies.
AB  - BACKGROUND: "Frailty" is an adverse, primarily gerontologic, health condition
      regarded as frequent with aging and having severe consequences. Although
      clinicians claim that the extremes of frailty can be easily recognized, a
      standardized definition of frailty has proved elusive until recently. This
      article evaluates the cross-validity, criterion validity, and internal validity
      in the Women's Health and Aging Studies (WHAS) of a discrete measure of frailty
      recently validated in the Cardiovascular Health Study (CHS). METHODS: The frailty
      measure developed in CHS was delineated in the WHAS data sets. Using latent class
      analysis, we evaluated whether criteria composing the measure aggregate into a
      syndrome. We verified the criterion validity of the measure by testing whether
      participants defined as frail were more likely than others to develop adverse
      geriatric outcomes or to die. RESULTS: The distributions of frailty in the WHAS
      and CHS were comparable. In latent class analyses, the measures demonstrated
      strong internal validity vis a vis stated theory characterizing frailty as a
      medical syndrome. In proportional hazards models, frail women had a higher risk
      of developing activities of daily living (ADL) and/or instrumental ADL
      disability, institutionalization, and death, independently of multiple
      potentially confounding factors. CONCLUSIONS: The findings of this study are
      consistent with the widely held theory that conceptualizes frailty as a syndrome.
      The frailty definition developed in the CHS is applicable across diverse
      population samples and identifies a profile of high risk of multiple adverse
      outcomes.

PMID- 16567376
TI  - Cholinergically mediated augmentation of cerebral perfusion in Alzheimer's
      disease and related cognitive disorders: the cholinergic-vascular hypothesis.
AB  - The treatment of Alzheimer's disease (AD) with cholinesterase inhibitors (ChEIs)
      is based on the cholinergic hypothesis. This hypothesis fails to account for the
      global nature of the clinical effects of ChEIs, for the replication of these
      effects in other dementias, and for the strong and unpredictable intraindividual
      variation in response to treatment. These findings may be better explained by the
      premise that ChEIs primarily act by augmenting cerebral perfusion: the
      cholinergic-vascular hypothesis. This article will review the evidence from
      preclinical and clinical investigations on the vascular role of the cholinergic
      neural system. The clinical relevance of this hypothesis is discussed with
      respect to its interactions with the vascular and amyloid hypotheses of AD.
      Implications for treatment are indicated. Finally, we propose that the role of
      the cholinergic system in neurovascular regulation and functional hyperemia
      elucidates how the cholinergic deficit in AD contributes to the clinical and
      pathological features of this disease.

PMID- 16567377
TI  - The effect of prior disability history on subsequent functional transitions.
AB  - BACKGROUND: Many older persons experience multiple transitions between states of
      disability and independence, but little is known about the effect of prior
      disability history on subsequent functional transitions. Our objective was to
      determine the effect of prior disability on subsequent transitions between no
      disability, mild disability, severe disability, and death. METHODS: For 60
      months, 754 persons aged 70 or older underwent monthly assessments of disability
      in basic activities of daily living. We used a multistate extension of the
      proportional hazards model to determine the effects of amount, defined as
      cumulative duration, and distribution, defined as number of episodes, of prior
      disability on subsequent functional transitions, adjusted for age, gender,
      cognitive status, timed gait, and habitual physical activity. RESULTS: For each
      additional month of prior disability, participants were more likely to make
      transitions representing new or worsening disability and were less likely to make
      transitions from disability to independence or from severe disability to death.
      Adjusting for the cumulative duration of prior disability, more episodes of prior
      disability were associated with a higher likelihood of most transitions,
      representing both increasing and decreasing disability, but had no effect on
      transitions to death. CONCLUSIONS: Both the amount and distribution of prior
      disability are important determinants of the likelihood of subsequent functional
      transitions. Analytic methods that account for prior disability history should be
      used in studies of functional transitions, and new measures of disability burden
      are needed that incorporate distribution as well as amount of disability.

PMID- 16567378
TI  - Lower plasma vitamin E levels are associated with the frailty syndrome: the
      InCHIANTI study.
AB  - BACKGROUND: The primary biologic mechanism that causes frailty in older persons
      has never been adequately explained. According to recent views, oxidative stress
      may be the driving force of this condition. We tested the hypothesis that,
      independent of confounders, low plasma levels of vitamin E (alpha-tocopherol),
      the main fat-soluble human antioxidant, are associated with the frailty syndrome
      in older persons free from dementia and disability. METHODS: The study sample
      included 827 older (> or =65 years) persons (women, 54%) who participated in a
      population-based epidemiological study. Frail participants were identified based
      on the presence of at least three of five of the following features: self
      reported weight loss, low energy, slow gait speed, low grip strength, and low
      physical activity. Participants with none of these features were considered
      nonfrail, while participants with one or two were considered intermediate frail.
      Plasma vitamin E levels were determined using reverse-phase high-performance
      liquid chromatography. Measured confounders included lower extremity muscle
      strength, cognitive function, diseases, and factors related to vitamin E
      metabolism. RESULTS: Age- and gender-adjusted levels of vitamin E decreased
      gradually from the nonfrail to the frail group (p for trend =.015). In the
      logistic model adjusted for multiple potential confounders, participants in the
      highest vitamin E tertile were less likely to be frail than were participants in
      the lowest vitamin E tertile (odds ratio, 0.30; 95% confidence interval, 0.10
      0.91). CONCLUSIONS: Our findings show an association between low circulating
      levels of one of the most important components of the human antioxidant system
      and the presence of frailty.

PMID- 16567379
TI  - Association of inflammatory markers with socioeconomic status.
AB  - BACKGROUND: This study examines the association between socioeconomic status
      (SES) and inflammatory markers in well-functioning older adults and seeks to
      determine whether any association remains after adjusting for biomedical and
      behavioral factors typically related to elevated serum levels of inflammatory
      markers. METHODS: Data were obtained from 3044 men and women, aged 70-79 from
      Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health,
      Aging and Body Composition study. Three indicators of SES were used: education,
      income, and ownership of financial assets. Serum levels of interleukin-6, C
      reactive protein, and tumor necrosis factor-alpha were measured. RESULTS: Low SES
      was associated with significantly elevated levels of interleukin-6, C-reactive
      protein, and tumor necrosis factor-alpha compared to high SES. Behavioral factors
      (including smoking, drinking, obesity) explained a substantial part of the
      inverse association between SES and inflammatory markers. Adjustment for
      prevalent diseases (including heart diseases, lung disease, and diabetes)
      associated with inflammation explained less of the association. CONCLUSIONS: This
      study suggests that interventions to improve health behaviors, even in old age
      and especially in low SES groups, may be useful in reducing risks associated with
      inflammation.

PMID- 16567380
TI  - Longitudinal changes during aging using proton magnetic resonance spectroscopy.
AB  - OBJECTIVE: We aimed to examine the longitudinal change in proton magnetic
      resonance spectroscopy ((1)H-MRS) visible metabolites (N-acetyl aspartate [NAA],
      creatine [Cr], choline [Cho], and myo-Inositol [mI]) in brains of elderly
      individuals over 3 years and relate them to cognitive function. METHODS:
      Neurologically and psychiatrically normal volunteers (n = 40) were examined at
      baseline and 3 years later with (1)H-MRS in two voxels (frontal white matter n =
      29, and occipitoparietal gray matter n = 36) and with detailed neuropsychological
      assessments. Longitudinal analyses were performed with age, educational level,
      sex, and white matter hyperintensities (WMH) in voxels as covariates. RESULTS:
      Frontal mI was significantly increased over time in male participants, but all
      other metabolites were stable over time. Neuropsychological performance was not
      significantly changed over 3 years, and there was no relationship between change
      in metabolite levels and change in neuropsychological function. CONCLUSIONS: MRS
      visible metabolites are stable in elderly persons over 3 years, with the
      exception of mI which shows an increase. Increasing mI may be a marker of aging
      or a preclinical neurodegenerative process. MRS changes do not correlate with
      change in neurocognitive function during aging.

PMID- 16567381
TI  - Effects of an ad libitum, high carbohydrate diet and aerobic exercise training on
      insulin action and muscle metabolism in older men and women.
AB  - BACKGROUND: Previous studies have demonstrated that aerobic exercise training and
      weight loss have independent effects on insulin-stimulated glucose disposal
      (ISGD). We hypothesized that ad libitum consumption of a high-carbohydrate diet
      would result in weight loss and improved ISGD, and that aerobic exercise training
      would facilitate greater improvements in ISGD compared with diet alone. METHODS:
      Older participants (13 women, 9 men; age = 66 +/- 1 year) with impaired glucose
      tolerance were randomly assigned to an ad libitum diet alone (18% fat, 19%
      protein, 63% carbohydrate) or this diet plus aerobic exercise training (4 d/wk,
      45 min/d, 80% VO(2peak)) for 12 weeks. ISGD, abdominal fat distribution, muscle
      glycogen, and glycogen synthase activity were assessed pre- and postintervention.
      RESULTS: Consumption of the diet resulted in significant weight loss and an
      improvement in ISGD. Consumption of the diet plus exercise training also resulted
      in weight loss and increased ISGD, but results were not significantly different
      from those in the diet-alone group. Mean abdominal visceral and subcutaneous
      adipose tissue cross-sectional areas were smaller postintervention compared to
      baseline with no difference between groups. Exercise training and consumption of
      the diet increased muscle glycogen content (344.7 +/- 21.3 to 616.7 +/- 34.4
      micromol.g(-1)) and decreased glycogen synthase activity (0.21 +/- 0.02 to 0.13
      +/- 0.01) compared to the diet alone. CONCLUSIONS: These results demonstrate that
      consumption of an ad libitum, high-carbohydrate diet alone or in combination with
      aerobic exercise training results in weight loss and improved insulin
      sensitivity. Furthermore, exercise combined with this diet appears to limit
      additional increases in insulin sensitivity due to muscle glycogen
      supercompensation with a concomitant adaptive response of glycogen synthase.

PMID- 16567382
TI  - Functional status of centenarians in Tokyo, Japan: developing better phenotypes
      of exceptional longevity.
AB  - BACKGROUND: Centenarians are sometimes said to be representative of lifelong
      healthy aging. Whether they are, in fact, examples of healthy aging remains a
      subject of debate. The existence of heterogeneity in functional status has been
      reported repeatedly in previous studies of centenarians. However, there is as yet
      no standardized classification system with which to describe their functional
      phenotype. METHODS: As part of a dynamic cohort study, we studied 304
      centenarians (65 men and 239 women) living in Tokyo. Their functional status
      (sensory, physical, and cognitive), which we used to represent their phenotype,
      was assessed and subsequently classified by standard assessment methods (simple
      questionnaire, Barthel index, Mini-Mental State Examination, and the Clinical
      Dementia Rating, respectively). RESULTS: We classified participants into 4
      categories according to their functional status. Only 5 (2%) were classified as
      "Exceptional," with all of their functions graded as excellent, and 56 (18%) were
      "Normal," exhibiting maintenance of fine cognitive and physical functions. One
      hundred sixty-seven (55%) were "Frail," exhibiting impairment of either cognitive
      or physical functions, and the remaining 76 (25%) were "Fragile," exhibiting
      deterioration of both physical and cognitive functions. CONCLUSIONS: The
      relationships between biochemical marker, mortality rates, lifestyle, and
      functional phenotypes demonstrated by this classification method indicate that
      the system is reliable to address the functional status of extremely old persons.
      Thus, this framework would be a useful tool for exploring the factors that
      contribute to exceptional longevity as well as those that help to maintain the
      functional status of the extremely old population.

PMID- 16567383
TI  - Universal metrics for quality assessment of protein identifications by mass
      spectrometry.
AB  - Increasing numbers of large proteomic datasets are becoming available. As
      attempts are made to interpret these datasets and integrate them with other forms
      of genomic data, researchers are becoming more aware of the importance of data
      quality with respect to protein identification. We present three simple and
      universal metrics that describe different aspects of the quality of protein
      identifications by peptide mass fingerprinting. Hit ratio gives an indication of
      the signal-to-noise ratio in a mass spectrum, mass coverage measures the amount
      of protein sequence matched, and excess of limit-digested peptides reflects the
      completeness of the digestion that precedes the peptide mass fingerprinting.
      Receiver-operating characteristic plots show that the novel metric, excess of
      limit-digested peptides, can discriminate between correct and random matches more
      accurately than search score when validating the results from a state-of-the-art
      protein identification software system (Mascot) especially when combined with the
      two other metrics, hit ratio and mass coverage. Recommendations are made
      regarding the use of the metrics when reporting protein identification
      experiments.

PMID- 16567384
TI  - Regulation of phosphatidylinositol 3-kinase by polyisoprenyl phosphates in
      neutrophil-mediated tissue injury.
AB  - Neutrophils play a central role in host defense, inflammation, and tissue injury.
      Recent findings indicate a novel role for polyisoprenyl phosphates (PIPPs) as
      natural down-regulatory signals in neutrophils. The relationship between PIPPs
      and neutrophil early activating signals, such as phosphoinositides, has not been
      previously determined. Here, we establish presqualene diphosphate (PSDP) as an
      endogenous PIPP regulator of phosphatidylinositol 3-kinase (PI3K). In human
      neutrophils, leukotriene B4 (LTB4) triggered rapid decreases in PSDP and
      reciprocal increases in PI3K activity. In addition, PSDP was identified by gas
      chromatography/mass spectrometry in p110gamma-PI3K immunoprecipitates obtained 30
      s after LTB4, indicating a physical interaction between PSDP and PI3K in
      activated neutrophils. Moreover, PSDP (0.4-800 pmol) directly inhibited
      recombinant human p110gamma-PI3K activity. During an experimental model of lung
      injury and inflammation, a reciprocal relationship was also present in vivo for
      lung PSDP and PI3K activity. To investigate its therapeutic potential, we
      developed a new PSDP structural mimetic that blocked human neutrophil activation
      and mouse lung PI3K activity and inflammation. Together, our findings indicate
      that PSDP is an endogenous PI3K inhibitor, and suggest that in inflammatory
      diseases characterized by excessive neutrophil activation, PIPPs can serve as
      structural templates in a novel antineutrophil therapeutic strategy to limit
      tissue injury.

PMID- 16567385
TI  - Secondary memory CD8+ T cells are more protective but slower to acquire a central
      memory phenotype.
AB  - The formation of memory CD8 T cells is an important goal of vaccination. However,
      although widespread use of booster immunizations in humans generates secondary
      and tertiary CD8 T cell memory, experimental data are limited to primary CD8 T
      cell memory. Here, we show that, compared with primary memory CD8 T cells,
      secondary memory CD8 T cells exhibit substantially delayed conversion to a
      central-memory phenotype, as determined by CD62L expression and interleukin (IL)
      2 production. This delayed conversion to a central-memory phenotype correlates
      with reduced basal proliferation and responsiveness to IL-15, although in vitro
      coculture with a high concentration of IL-15 is capable of inducing proliferation
      and CD62L upregulation. Functionally, secondary memory CD8 T cells are more
      protective in vivo on a per cell basis, and this may be explained by sustained
      lytic ability. Additionally, secondary memory CD8 T cells are more permissive
      than primary memory CD8 T cells for new T cell priming in lymph nodes, possibly
      suggesting a mechanism of replacement for memory T cells. Thus, primary and
      secondary memory CD8 T cells are functionally distinct, and the number of
      encounters with antigen influences memory CD8 T cell function.

PMID- 16567386
TI  - A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil
      recruitment in inflammatory arthritis.
AB  - Neutrophil recruitment into tissue plays an important role in host defense and
      disease pathogenesis, including the inflammatory arthritides. A multitude of
      diverse chemoattractants have been implicated in neutrophil recruitment,
      suggesting that they have overlapping functions in mediating this critical
      biological response. However, here we demonstrate a unique, non-redundant role
      for the leukotriene B4 receptor BLT1 in mediating neutrophil recruitment into the
      joint in the K/BxN mouse model of inflammatory arthritis. We demonstrate that
      neutrophil expression of BLT1 was absolutely required for arthritis generation
      and chemokine production in this model, and that specific BLT1 inhibition
      reversed established disease. Adoptive transfer of wild-type (WT) neutrophils
      restored arthritis and chemokine production in BLT1(-/-) mice. Surprisingly, the
      primary effect of the transferred WT neutrophils into BLT1(-/-) mice was to
      promote the entry of endogenous BLT1(-/-) neutrophils into the joints of these
      mice. However, continued joint inflammation was dependent on the presence of WT
      neutrophils, indicating an ongoing specific requirement for BLT1-activated
      neutrophils in mediating BLT1(-/-) neutrophil recruitment by other
      chemoattractants. These experiments demonstrate that neutrophil BLT1 functions in
      a novel and essential non-cell-autonomous manner to enable the recruitment of
      additional neutrophils not expressing this receptor, thereby amplifying the
      inflammatory response in autoantibody-induced arthritis.

PMID- 16567387
TI  - Impaired Langerhans cell migration in psoriasis.
AB  - We have examined whether psoriasis is associated with systemic effects on
      epidermal Langerhans cell (LC) function and, specifically, the migration of LCs
      from the skin. Compared with normal skin, the frequency and morphology of
      epidermal LCs in uninvolved skin from patients with psoriasis was normal.
      However, mobilization of these cells in response to stimuli that normally induce
      migration (chemical allergen, tumor necrosis factor alpha [TNF-alpha], and
      interleukin-1beta [IL-1beta]) was largely absent, despite the fact that treatment
      with TNF-alpha and IL-1beta was associated with comparable inflammatory reactions
      in patients and controls. The failure of LC migration from uninvolved skin was
      not attributable to altered expression of receptors for IL-1beta or TNF-alpha
      that are required for mobilization, nor was there an association with induced
      cutaneous cytokine expression. Although a role for altered dynamics of LC
      migration/turnover has not been formally excluded, these data reveal a very
      consistent decrement of LC function in psoriasis that may play a decisive role in
      disease pathogenesis.

PMID- 16567388
TI  - Neutrophil-derived leukotriene B4 is required for inflammatory arthritis.
AB  - Neutrophils serve as a vanguard of the acute innate immune response to invading
      pathogens. Neutrophils are also abundant at sites of autoimmune inflammation,
      such as the rheumatoid joint, although their pathophysiologic role is
      incompletely defined and relevant effector functions remain obscure. Using
      genetic and pharmacologic approaches in the K/BxN serum transfer model of
      arthritis, we find that autoantibody-driven erosive synovitis is critically
      reliant on the generation of leukotrienes, and more specifically on leukotriene
      B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular
      source for this mediator, we find via reconstitution experiments that mast cells
      are a dispensable source of leukotrienes, whereas arthritis susceptibility can be
      restored to leukotriene-deficient mice by intravenous administration of wild-type
      neutrophils. These experiments demonstrate a nonredundant role for LTB4 in
      inflammatory arthritis and define a neutrophil mediator involved in orchestrating
      the synovial eruption.

PMID- 16567389
TI  - Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine
      ileitis.
AB  - L-selectin ligands might be relevant for inflammatory cell trafficking into the
      small intestine in a spontaneous model of chronic ileitis (i.e., SAMP1/YitFc
      mice). Immunoblockade of peripheral node addressin or mucosal addressin cell
      adhesion molecule 1 failed to ameliorate ileitis, whereas P-selectin glycoprotein
      ligand 1 (PSGL-1) neutralization attenuated both the adoptively transferred and
      spontaneous disease. PSGL-1 was detected in venules of mesenteric lymph node and
      small intestine by immunohistochemistry and confirmed by real-time reverse
      transcription polymerase chain reaction and flow cytometry. In addition,
      reconstitution of wild-type mice with PSGL-1(-/-) bone marrow demonstrated that
      PSGL-1 messenger RNA and PSGL-1 protein expression remained on endothelium,
      localized within mesenteric lymph node and small intestine. Endothelial PSGL-1
      bound P-selectin-IgG and its blockade or genetic deletion altered the recruitment
      of lymphocytes to the small intestine, as revealed by intravital microscopy and
      homing studies. Endothelial expression of PSGL-1 adds a new dimension to the
      various cellular interactions involved in small intestinal recruitment. Thus, the
      multiple roles of PSGL-1 may explain why targeting this single adhesion molecule
      results in attenuation of chronic murine ileitis, a disease previously resistant
      to antiadhesion molecule strategies.

PMID- 16567390
TI  - CD4+ T cells that enter the draining lymph nodes after antigen injection
      participate in the primary response and become central-memory cells.
AB  - We explored the relationship between the time of naive CD4+ T cell exposure to
      antigen in the primary immune response and the quality of the memory cells
      produced. Naive CD4+ T cells that migrated into the skin-draining lymph nodes
      after subcutaneous antigen injection accounted for about half of the antigen
      specific population present at the peak of clonal expansion. These late-arriving
      T cells divided less and more retained the central-memory marker CD62L than the T
      cells that resided in the draining lymph nodes at the time of antigen injection.
      The fewer cell divisions were related to competition with resident T cells that
      expanded earlier in the response and a reduction in the number of dendritic cells
      displaying peptide-major histocompatibility complex (MHC) II complexes at later
      times after antigen injection. The progeny of late-arriving T cells possessed the
      phenotype of central-memory cells, and proliferated more extensively during the
      secondary response than the progeny of the resident T cells. The results suggest
      that late arrival into lymph nodes and exposure to antigen-presenting cells
      displaying lower numbers of peptide-MHC II complexes in the presence of competing
      T cells ensures that some antigen-specific CD4+ T cells divide less in the
      primary response and become central-memory cells.

PMID- 16567392
TI  - Clostridium septicum infections in children: a case report and review of the
      literature.
AB  - Clostridium myonecrosis is a rare and deadly infection that progresses very
      rapidly; thus, prompt diagnosis and treatment is vital. In adults, clostridial
      myonecrosis used to be a well-known complication of war wounds. Today, it is
      usually seen in settings of trauma, surgery, malignancy, skin infections/burns,
      and septic abortions. More recently, cases of nontraumatic or spontaneous
      clostridial myonecrosis have been reported in both adults and children.
      Clostridium perfringens and Clostridium septicum are responsible for the majority
      of the clinically relevant infections. Higher mortality rates are seen when C
      septicum is the causative agent. Here we present a child who survived a severe
      case of C septicum myonecrosis involving both abdominal and thoracic cavities.
      This rare infection has a high mortality rate and might be easily misdiagnosed in
      children, even by experienced clinicians, because of its nonspecific
      presentation. We also review all reported pediatric cases of C septicum infection
      and myonecrosis and discuss the surgical and medical interventions associated
      with improved survival. We identified a total of 47 cases of C septicum
      infection; of these, 22 (47%) were cases of C septicum associated with
      myonecrosis. Several factors, if available, were analyzed for each case: age,
      gender, infection location, previous diagnoses, presenting signs and symptoms,
      neutropenia, gross pathology of the colon, antibiotic use, surgical intervention,
      and final outcome. We found that conditions related with C septicum infection in
      children can be grouped into 3 major categories: patients with neutrophil
      dysfunction; patients with associated bowel ischemia; and patients with a history
      of trauma. Malignancies were found in 49% of the cases, cyclic or congenital
      neutropenia in 21%, hemolytic-uremic syndrome in 11%, structural bowel ischemia
      in 4%, and local extremity trauma in 6%. In addition, 6% of the cases had no
      known underlying disorder. Abdominal symptoms including vomiting, diarrhea, blood
      per rectum, abdominal pain, anorexia, and/or acute abdomen, were reported in 85%
      of the children. Fever was also a common finding. The mainstay of treatment for C
      septicum infection was parenteral antibiotics and/or surgical intervention. The
      mortality rate for children with C septicum infection and myonecrosis was 57% and
      59%, respectively. Although 82% of all cases received antibiotics, only 43%
      underwent therapeutic surgical intervention. Several clinical factors were found
      to be associated with improved survival. Only 35% of the children with
      gastrointestinal tract involvement survived, compared with 86% of the children
      without gastrointestinal tract involvement. The survival rates for other
      conditions ranged from 0% to 50%. One hundred percent survival was reported in
      patients with no previously diagnosed conditions and those with infections
      resulting from trauma to the extremities. All survivors received antibiotic
      treatment, compared with only 68% of the nonsurvivors. Most survivors (84%)
      underwent therapeutic surgical intervention, compared with only 12% of
      nonsurvivors. Other treatments were used adjunctively, including hyperbaric
      oxygen, granulocyte colony-stimulating factor, granulocyte transfusions, and
      intravenous immunoglobulin. C septicum infections in children are often fatal;
      thus, one needs to have a high index of suspicion in at-risk patients. This
      review describes who these patients are, their clinical presentation, and the
      therapeutic strategies associated with improved survival.

PMID- 16567391
TI  - CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer.
AB  - Chronic inflammation is a well-known risk factor for cancer. Proinflammatory
      mediators such as prostaglandin E2 (PGE2) promote colorectal tumor growth by
      stimulating angiogenesis, cell invasion, and cell growth, and inhibiting
      apoptosis. Molecules that regulate tumor-associated angiogenesis provide
      promising therapeutic targets for treatment of colorectal cancer (CRC) as
      indicated by the recent development of the novel anti-angiogenic agent
      bevacizumab (Avastin). However, use of this drug only prolongs survival by
      several months, highlighting the importance of finding more effective treatment
      regimens. We report here that PGE2 induces expression of CXCL1 (growth-regulated
      oncogene alpha), a pro-angiogenic chemokine, in human CRC cells. More
      importantly, CXCL1 released from carcinoma cells induces microvascular
      endothelial cell migration and tube formation in vitro. Furthermore, PGE2
      promotes tumor growth in vivo by induction of CXCL1 expression, which results in
      increased tumor microvessel formation. These results have potential clinical
      significance because we found that CXCL1 expression correlates with PGE2 levels
      in human CRCs. Collectively, our findings show for the first time that CXCL1 is
      regulated by PGE2 and indicate that CXCL1 inhibitors should be evaluated further
      as potential anti-angiogenic agents for treatment of CRC.

PMID- 16567393
TI  - The effect of timing of cord clamping on neonatal venous hematocrit values and
      clinical outcome at term: a randomized, controlled trial.
AB  - BACKGROUND: The umbilical cord is usually clamped immediately after birth. There
      is no sound evidence to support this approach, which might deprive the newborn of
      some benefits such as an increase in iron storage. OBJECTIVES: We sought to
      determine the effect of timing of cord clamping on neonatal venous hematocrit and
      clinical outcome in term newborns and maternal postpartum hemorrhage. METHODS:
      This was a randomized, controlled trial performed in 2 obstetrical units in
      Argentina on neonates born at term without complications to mothers with
      uneventful pregnancies. After written parental consents were obtained, newborns
      were randomly assigned to cord clamping within the first 15 seconds (group 1), at
      1 minute (group 2), or at 3 minutes (group 3) after birth. The infants' venous
      hematocrit value was measured 6 hours after birth. RESULTS: Two hundred seventy
      six newborns were recruited. Mean venous hematocrit values at 6 hours of life
      were 53.5% (group 1), 57.0% (group 2), and 59.4% (group 3). Statistical analyses
      were performed, and results were equivalent among groups because the hematocrit
      increase in neonates with late clamping was within the prespecified physiologic
      range. The prevalence of hematocrit at <45% (anemia) was significantly lower in
      groups 2 and 3 than in group 1. The prevalence of hematocrit at >65% was similar
      in groups 1 and 2 (4.4% and 5.9%, respectively) but significantly higher in group
      3 (14.1%) versus group 1 (4.4%). There were no significant differences in other
      neonatal outcomes and in maternal postpartum hemorrhage. CONCLUSIONS: Delayed
      cord clamping at birth increases neonatal mean venous hematocrit within a
      physiologic range. Neither significant differences nor harmful effects were
      observed among groups. Furthermore, this intervention seems to reduce the rate of
      neonatal anemia. This practice has been shown to be safe and should be
      implemented to increase neonatal iron storage at birth.

PMID- 16567394
TI  - Preterm growth restraint: a paradigm that unifies intrauterine growth retardation
      and preterm extrauterine growth retardation and has implications for the small
      for-gestational-age indication in growth hormone therapy.

PMID- 16567395
TI  - Diacetylated derivatives of spermine and spermidine as novel promising tumor
      markers.
AB  - N1,N12-diacetylspermine (DiAcSpm) and N1,N8-diacetylspermidine (DiAcSpd) are
      minor components of human urinary polyamine to which little attention has been
      paid until recently. HPLC analysis of urinary polyamines has revealed that the
      excretion of these diacetylpolyamines, in particular, into urine was frequently
      and markedly increased in association with every type of cancer so far examined.
      Remission was usually accompanied by recovery of urinary diacetylpolyamines to
      the normal level. DiAcSpm was more sensitive than CEA for detecting colorectal
      cancer patients, while DiAcSpd was highly specific for malignant conditions in
      that the excretion of the latter was scarcely elevated in cases of benign
      urogenital diseases. An ELISA procedure for rapid determination of DiAcSpm was
      developed to promote the clinical application of these new tumor markers, and
      subsequent studies indicated that DiAcSpm was elevated in 60% of colorectal
      cancer patients at early stages (stage 0 + I), whereas only 10% of these patients
      were CEA-positive. DiAcSpm may also be useful as a follow-up marker that is
      efficient for detecting recurrence and sensitive to changes in the clinical
      condition of patients. The evidence accumulated so far indicates that DiAcSpm and
      DiAcSpd are promising novel tumor markers. They deserve more intensive studies,
      including studies of their biochemistry and metabolism.

PMID- 16567397
TI  - Lymphocyte toxicity of prion fragments.
AB  - Prion protein fragments that are extracted from the brains of patients with
      Gerstmann-Straussler-Scheinker disease are known to have stimulating action on
      circulating leukocytes. In particular, the amyloidogenic hydrophobic prion
      peptide HuPrP (113-127) AGAAAAGAVVGGLGG has been reported to be associated with
      significant cellular toxicity. In this paper we show that the self assembled form
      of HuPrP (113-127) and its valine rich domains viz. GAVVGGLG [HuPrP (119-126)]
      and VVGGLGG [HuPrP (121-127)] are toxic to peripheral lymphocytes. To explore the
      cytotoxic mechanism of these fragments, we studied 3-(4,5-dimethylthiazol-2yl)-2
      5-diphenyltetrazolium bromide (MTT) reduction, reactive oxygen species (ROS)
      generation, calcium influx and raft sequestration of' peptide treated
      lymphocytes. Langmuir monolayer studies on these peptides showed a maximum lipid
      perturbing property of HuPrP (121-127) as compared to the other two fragments.
      MTT reduction assays on lymphocytes treated with peptides indicated that the
      prion peptide fibrils are relatively more toxic than freshly solubilized peptide
      preparations. Lymphocytes treated with HuPrP (121-127), HuPrP (113-127) and HuPrP
      (119-126) fibrils underwent 60%, 30% and 40% cell death, respectively. Abeta(1
      42), HuPrP (119-126) and HuPrP (121-127) fibrils caused 4 fold increases in
      intracellular ROS as compared with control cells. However, HuPrP (113-127)
      fibrils lacked such a significant ROS generating activity, indicating that a
      subtle difference in sequence leads to a difference in the toxic mechanism in the
      cell. HuPrP (119-126) and HuPrP (121-127) fibrils also produced maximum raft
      sequestration and calcium influx. Taken together, these data suggest that the
      assemblage of prion fragments has significant toxic activity on peripheral
      lymphocytes, a finding with implications for controlling reactive lymphocytes in
      prion infected subjects.

PMID- 16567396
TI  - Application of lectin microarray to crude samples: differential glycan profiling
      of lec mutants.
AB  - We recently developed a novel system for lectin microarray based on the
      evanescent-field fluorescence-detection principle, by which even weak lectin
      oligosaccharide interactions are detectable without a washing procedure. For its
      practical application, cell glycan analysis was performed for Chinese hamster
      ovary (CHO) cells and their glycan profile was compared with those of their
      glycosylation-defective Lec mutants. Each of the cell surface extracts gave a
      significantly different profile from that of the parental CHO cells in a manner
      reflecting denoted biosynthetic features. Hence, the developed lectin microarray
      system is considered to be fully applicable for differential glycan profiling of
      crude samples.

PMID- 16567398
TI  - Novel heparanase-inhibiting antibody reduces neointima formation.
AB  - Basic fibroblast growth factor (bFGF), stored bound to heparan sulfate
      proteoglycans in the extracellular matrix (ECM) of the arterial media, may
      initiate smooth muscle cell (SMC) proliferation after coronary intervention, thus
      contributing to restenosis. bFGF mobilization from ECM stores after injury may be
      induced by platelet degranulation products such as heparanase. Therapies aimed at
      the inhibition of bFGF release and activation may assist in prevention of
      restenosis. To test this theory, we first examined the mobilization and
      activation of bFGF in the arterial media by platelet-derived heparanase.
      Heparanase, locally delivered to the rat carotid artery, was found to release
      bFGF and induce substantial SMC proliferation in the absence of actual vascular
      injury. An antibody that neutralizes heparanase was then developed and evaluated
      in a rat carotid balloon injury model. Local delivery of anti-heparanase IgG was
      found to inhibit bFGF release by approximately 60% ( p < 0.001) at 4 d; this
      correlated with the significant reduction in neointima formation observed at 14 d
      (intimal area/medial area: control 1.3 +/- 0.3, anti-heparanase 0.35 +/- 0.12, p
      < 0.0001). Platelet-derived heparanase is therefore likely to be important in
      initiating events leading to restenosis via bFGF mobilization. Furthermore,
      heparanase neutralization may assist in the prevention of restenosis following
      vascular injury.

PMID- 16567399
TI  - Phylogeny of vertebrate Src tyrosine kinases revealed by the epitope region of
      mAb327.
AB  - Mass fingerprinting and MS/MS analysis demonstrated that Xyk, a 57-kDa Src family
      tyrosine kinase that is activated within minutes of Xenopus egg fertilization,
      comprises a mixture of two Src proteins, Src1 and Src2. However, the Xenopus Src
      protein, denoted as xSrc, is hardly detectable with mAb327, a universal Src
      specific antibody, whose target sequence has not yet been determined. We show
      that a point amino acid substitution in the Src homology 3 domain of xSrc is
      critical for improvement of the low efficiency of its recognition by mAb327.
      Namely, a point-mutated xSrc, in which Arg-121 was replaced by His that is
      conserved among mAb327-reactive Src in mammals and chicken, showed increased
      recognition by mAb327. On the other hand, a mutant chicken Src, in which the His
      122 residue is replaced by Arg, showed decreased recognition by mAb327. Genomic
      sequencing analysis also demonstrated that reptile Src proteins are of either the
      R-type (snake) or H-type (caiman, turtle, and tortoise). These studies revealed,
      for the first time, a critical amino acid in the Src SH3 domain for mAb327
      recognition, and suggest a novel scheme for the molecular evolution of Src, in
      which the H-type Src(s) are monophyletic and derived from the R-type Src.

PMID- 16567400
TI  - A novel sulfotransferase abundantly expressed in the dauer larvae of
      Caenorhabditis elegans.
AB  - We have isolated a gene (clone Y113G7A.11) from Caenorhabditis elegans (C.
      elegans), that we have designated as ceST1, and which is the only member of the
      cytosolic sulfotransferase (SULT) gene family present in the genome of this
      organism. We identified the SULT motifs of ceST1 based upon their deduced amino
      acid sequence, and subsequently expressed the ceST1 cDNA in Escherichia coli and
      characterized its enzymatic properties. The recombinant protein showed sulfation
      activity for 4-nitrophenol and 2-naphthol substrates, but did not catalyze the
      sulfation of either monoamines or hydroxysteroids. Another compound sulfated by
      ceST1 is bisphenol A, which is known to stimulate germ cell proliferation in C.
      elegans. SULT activity was not detected in the cytosol of C. elegans, probably
      due to heat labile inhibitors. The ceST1 protein was detectable in the cytosol of
      C. elegans using anti-sera raised against recombinant ceST1, and transcripts
      could also be detected throughout the developmental stages. Moreover, high levels
      of ceST1 expression were evident at both the embryonic and adult stages and were
      augmented in dauer larva. These findings suggest that this sulfotransferase
      either forms part of a defence system against xenobiotics or regulates germ cell
      proliferation in C. elegans.

PMID- 16567402
TI  - Up-regulation of heme biosynthesis during differentiation of Neuro2a cells.
AB  - Heme is an iron-containing tetrapyrrole molecule that functions as a prosthetic
      group for proteins such as mitochondrial respiratory enzymes. Several studies
      have suggested that heme has essential functions in the construction and
      maintenance of the nervous system. In this study, the contents of three
      biologically important forms of heme (types a, b, and c) and the expression of
      heme biosynthetic enzymes were examined in differentiating Neuro2a cells. During
      neuronal differentiation, there were increases in the cellular heme levels and
      increases in the mRNA levels for the rate-limiting enzymes of heme biosynthesis,
      such as aminolevulinic acid synthase (ALAS; EC 2.3.1.37) and coproporphyrinogen
      oxidase (EC 1.3.3.3). With respect to heme contents, heme b increased in the late
      phase of differentiation, but no apparent increase in heme a or b was observed in
      the early phase. In contrast, heme c (cytochrome c) markedly increased during the
      early phase of differentiation. This change preceded the increase in heme b and
      the up-regulation of the mRNA levels for heme biosynthetic enzymes. This study
      suggests the up-regulation of heme biosynthesis and differential regulation of
      the heme a, b, and c levels during neuronal differentiation.

PMID- 16567401
TI  - Processing of human cathepsin D is independent of its catalytic function and auto
      activation: involvement of cathepsins L and B.
AB  - The current mechanism proposed for the processing and activation of the 52 kDa
      lysosomal aspartic protease cathepsin D (cath-D) is a combination of partial auto
      activation generating a 51 kDa pseudo-cath-D, followed by enzyme-assisted
      maturation involving cysteine and/or aspartic proteases and yielding successively
      a 48 kDa intermediate and then 34 + 14 kDa cath-D mature species. Here we have
      investigated the in vivo processing of human cath-D in a cath-D-deficient
      fibroblast cell line in order to determine whether its maturation occurs through
      already active cath-D and/or other proteases. We demonstrate that cellular cath-D
      is processed in a manner independent of its catalytic function and that auto
      activation is not a required step. Moreover, the cysteine protease inhibitor E-64
      partially blocks processing, leading to accumulation of 52-48 kDa cath-D
      intermediates. Furthermore, two inhibitors, CLICK148 and CA-074Met, specific for
      the lysosomal cath-L and cath-B cysteine proteases induce accumulation of 48 kDa
      intermediate cath-D. Finally, maturation of endocytosed pro-cath-D is also
      independent of its catalytic function and requires cysteine proteases. We
      therefore conclude that the mechanism of cath-D maturation involves a fully
      assisted processing similar to that of pro-renin.

PMID- 16567403
TI  - Characterization and application of a novel RNA aptamer against the mouse prion
      protein.
AB  - In order to isolate RNA aptamers against the mouse prion protein (mPrP), we
      carried out in vitro selection from RNA pools containing a 30-nucleotide
      randomized region. Aptamer 60-3 was found to have a high affinity for mPrP (K(d)
      = 5.6 +/- 1.5 nM), and 2'-fluoro-pyrimidine modifications for RNase resistance
      did not abolish its binding activity (K(d) = 22 +/- 4 nM). Following 5'
      biotinylation, aptamer 60-3 specifically detected PrP in mouse brain homogenate
      in a Northwestern blotting assay. To determine the mPrP-aptamer binding region,
      we performed protein-deletion-mutant analysis and competition-binding analysis
      using heparin. The results showed that aptamer 60-3 appears to have binding sites
      located between amino acids 23-108.

PMID- 16567404
TI  - Loss of core fucosylation of low-density lipoprotein receptor-related protein-1
      impairs its function, leading to the upregulation of serum levels of insulin-like
      growth factor-binding protein 3 in Fut8-/- mice.
AB  - alpha1,6-Fucosyltransferase (Fut8) catalyzes the transfer of a fucose residue
      from GDP-fucose to the innermost N-acetylglucosamine residue of N-glycans. Here
      we report that the loss of core fucosylation impairs the function of low-density
      lipoprotein (LDL) receptor-related protein-1 (LRP-1), a multifunctional scavenger
      and signaling receptor, resulting in a reduction in the endocytosis of insulin
      like growth factor (IGF)-binding protein-3 (IGFBP-3) in the cells derived from
      Fut8-null (Fut8-/-) mice. The reduced endocytosis was restored by the re
      introduction of Fut8. Serum levels of IGFBP-3 were markedly upregulated in Fut8-/
      mice. These data clearly indicate that core fucosylation is crucial for the
      scavenging activity of LRP-1 in vivo.

PMID- 16567405
TI  - Identification and characterization of a neutralizing monoclonal antibody for the
      epitope on HM-1 killer toxin.
AB  - Killer toxin-neutralizing monoclonal antibody (nmAb-KT) against HM-1 killer toxin
      (HM-1) produced by yeast Williopsis saturnus var. mrakii IFO 0895 reduces both
      the killing and glucan synthase inhibitory activity of HM-1. nmAb-KT is
      classified as IgG1kappa and has been shown to be ineffective against HYI killer
      toxin produced by the related yeast W. saturnus var. saturnus IFO 0117. To
      determine the epitope for nmAb-KT, overlapping peptides were synthesized from the
      primary structure of HM-1. nmAb-KT reacted with peptides P5 (33NVHWMVTGGST43), P6
      (39TGGSTDGKQG48) and P7 (44DGKQGCATIWEGS56), which represent the middle region of
      the HM-1 sequence. P6 reacted most strongly with nmAb-KT. Combined analysis by
      immunoblotting, surface plasmon resonance (SPR) analysis and yeast growth
      inhibition assay showed that nmAb-KT recognizes a specific epitope within peptide
      P6. The K(d) value of nmAb-KT against HM-1 and P6 were determined to be 5.48 x
      10(-9) M and 1.47 x 10(-6) M by SPR analysis, respectively. These results
      strongly indicate that nmAb-KT binds to HM-1 at the sequence 41GSTDGK46, and not
      to HYI at the same position. The potential active site of HM-1 involved in the
      killing activity against sensitive yeast is discussed.

PMID- 16567406
TI  - Multiple structural transitions of the GroEL subunit are sensitive to
      intermolecular interactions with cochaperonin and refolding polypeptide.
AB  - In this study we attempted to determine the specific roles of the numerous
      conformational changes that are observed in the bacterial chaperonin GroEL, by
      performing stopped-flow experiments on GroEL R231W in the presence of a refolding
      substrate protein. The apparent rate of one kinetic phase was decreased by
      approximately 25% in the presence of prebound unfolded malate dehydrogenase while
      another phase was suppressed completely under the same conditions, reflecting
      different effects of the unfolded protein on multiple structural transitions
      within GroEL. The addition of cochaperonin GroES counteracts the effect of the
      bound substrate protein in the former case, but had no effect on the latter, more
      extensive suppression. Using a chemically modified form of GroEL R231W which is
      incapable of releasing substrate proteins at low temperatures, we identified a
      conformational transition that is implicated in the release of substrate
      proteins. Parts of the actual process of substrate protein release were also
      observed through fluorescence resonance energy transfer experiments involving
      GroEL and labeled substrate protein. Analysis of the energy transfer data
      revealed an interesting relationship between substrate protein displacement and a
      specific structural transition in the GroEL apical domain.

PMID- 16567407
TI  - Probing the catalytic center of porcine aminoacylase 1 by site-directed
      mutagenesis, homology modeling and substrate docking.
AB  - Three-dimensional structural models of porcine aminoacylase 1 (pACY1) were
      constructed by homology modeling and aligning the structures of members of the
      M20 peptidase family. After energy minimization and quality evaluation, the best
      model from the homology modeling was chosen for docking with the best substrate
      (N-acetyl-L-methionine). The most reasonable binding mode was found among a large
      number of predicted complexes by using clustering analysis and screening with
      expert knowledge. Structural analysis revealed that the zinc ion is not likely to
      bind to the substrate, and that Arg348 and Glu146 play vital roles in binding and
      catalysis. In the site-directed mutagenesis experiments, mutation of His79,
      Asp112, Glu147, Arg348, and Glu146, resulted in significant reductions of
      specific activity, while the wild-type pACY1 overexpressed in Rosetta (DE3) had
      almost as high a specific activity as the native enzyme. On the basis of these
      observations, we proposed a revised catalytic mechanism for this metalloenzyme.

PMID- 16567408
TI  - Evaluation of the dynamic structure of DsrA RNA from E. coli and its functional
      consequences.
AB  - DsrA RNA is an 87-nucleotide regulatory non-protein-coding RNA of Escherichia
      coli for which two secondary structure models (I and II) have been proposed. We
      have compared these models by the energy calculations, which revealed that the
      currently accepted model II should be rejected on the basis of thermodynamics.
      Here we provide new results of nuclease footprinting analysis and the application
      of RNA technologies that have not previously been used for DsrA RNA structural
      studies, such as hydrolysis with RNase H, DNAzyme, hydroxyl radicals and lead.
      These approaches together with bioinformatics calculations provided strong
      arguments for a new model III. This model clearly shows that the long U-rich
      region between hairpins 1 and 2 is double-stranded. These findings shed new light
      on DsrA RNA-Hfq interactions.

PMID- 16567409
TI  - Variation in the divalent cation requirements of influenza A virus N1
      neuraminidases.
AB  - Enzymatic kinetic parameters of influenza A virus N1 neuraminidases (NA)
      chromatographically purified from several vaccine candidate strains were tested.
      With ionic strength held constant, Ca2+ or Mg2+ increased the initial rate of
      enzymatic activity. The 1934 and 1943 strains had statistically significant
      highest initial velocities, V(max)/K(m) and V(max). There were no significant
      differences among the influenza virus strains from 1947 to 1991. Measured K(m)
      for the 1943 strain (6.2 x 10(-5) M) was significantly higher than other strains
      (3.1-4.7 x 10(-5) M). V(max)/K(m) varied from 0.78 M(-1) s(-1) to 0.91 M(-1) s(
      1) and V(max) varied from 3.0 s(-1) to 5.5 s(-1) before the addition of a
      divalent cation and increased approximately 2-fold for each of these kinetic
      parameters for each strain after the addition of exogenous Ca2+ or Mg2+. Dialysis
      reduced the initial velocity and immunogenicity of each strain with significant
      differences found among strains. Enzymatic activity and immunogenicity were
      partially restored by the addition of exogenous Ca2+. Nucleic acid sequence
      analysis could not predict these differences. Selection of vaccine strains must
      include analysis of antigenic changes, but also enzymatic studies and
      determination of the requirement of divalent cations to maintain immunogenicity
      and activity during production.

PMID- 16567410
TI  - Muscarinic acetylcholine receptors stimulate Ca2+ influx in PC12D cells
      predominantly via activation of Ca2+ store-operated channels.
AB  - Activation of muscarinic acetylcholine receptors (mAChRs) causes the rapid
      release of Ca2+ from intracellular stores and a sustained influx of external Ca2+
      in PC12D cells, a subline of the widely studied cell line PC12. Release of Ca2+
      from intracellular stores and a sustained influx of Ca2+ are also observed
      following exposure to thapsigargin, a sesquiterpene lactone that depletes
      intracellular Ca2+ pools by irreversibly inhibiting the Ca2+ pump of the
      endoplasmic reticulum. In this study, we show that carbachol and thapsigargin
      empty the same intracellular Ca2+ stores, and that these stores are a subset of
      intracellular stores depleted by the Ca2+ ionophore ionomycin. Intracellular Ca2+
      stores remain depleted during continuous stimulation of mAChR with carbachol in
      medium containing 2 mM extracellular Ca2+, but rapidly refill following
      inhibition of mAChRs with atropine. Addition of atropine to carbachol-stimulated
      cells causes intracellular Ca2+ levels to return to baseline levels in two steps:
      a rapid decrease that correlates with the reuptake of Ca2+ into internal stores
      and a delayed decrease that correlates with the inhibition of a Mn2+-permeable
      Ca2+ channel. Several lines of evidence suggest that carbachol and thapsigargin
      stimulate Ca2+ influx by a common mechanism: (i) pretreatment with thapsigargin
      occludes atropine-mediated inhibition of Ca2+ influx, (ii) carbachol and
      thapsigargin applied individually or together are equally efficient at
      stimulating the influx of Mn2+, and (iii) identical rates of Ca2+ influx are
      observed when Ca2+ is added to cells pretreated with carbachol, thapsigargin, or
      both agents in the absence of extracellular Ca2+. Taken together, these data
      suggest that the sustained influx of extracellular Ca2+ observed following
      activation of mAChRs in PC12D cells is mediated primarily by activation of a Mn2+
      permeable, Ca2+ store-operated Ca2+ channel.

PMID- 16567411
TI  - Muscarinic acetylcholine receptors activate TRPC6 channels in PC12D cells via
      Ca2+ store-independent mechanisms.
AB  - In this paper we report that stimulation of mAChRs in PC12D cells activates Ca2+
      channels that are regulated independently of intracellular Ca2+ stores. In
      nominally Ca2+-free medium, exposure of PC12D cells to carbachol stimulates a
      robust influx of Ba2+, a Ca2+ substitute. This influx is blocked by atropine, but
      not by inhibitors of the nicotinic acetylcholine receptor or L-, N-, or T-type
      voltage-regulated Ca2+ channels. By contrast, depletion of intracellular Ca2+
      stores with thapsigargin only weakly stimulates Ba2+ influx. Unlike store
      operated Ca2+ channels (SOCCs), which close only after intracellular Ca2+ stores
      refill, channels mediating carbachol-stimulated Ba2+ influx rapidly close
      following the inactivation of mAChRs with atropine. Ba2+ influx is inhibited by
      extracellular Ca2+, by the Ca2+ channel blocker SKF-96365, and by activation of
      protein kinase C (PKC). Exogenous expression of antisense RNA encoding the rat
      canonical-transient receptor potential Ca2+ channel subtype 6 (TRPC6) or the N
      terminal domain of TRPC6 blocks carbachol-stimulated Ba2+ influx in PC12D cells.
      Expression of TRPC6 antisense RNA or the TRPC6 N-terminal domain also blocks Ba2+
      influx stimulated by 1-oleoyl-2-acetyl-sn-glycerol (OAG), a diacylglycerol analog
      previously shown to activate exogenously expressed TRPC6 channels. These data
      show that mAChRs in PC12D cells activate endogenous Ca2+ channels that are
      regulated independently of Ca2+ stores and require the expression of TRPC6.

PMID- 16567412
TI  - Freshwater bioluminescence in Vibrio albensis (Vibrio cholerae biovar albensis)
      NCIMB 41 is caused by a two-nucleotide deletion in luxO.
AB  - We previously proposed that the function of the lux operon is to produce a
      halotolerant flavodoxin, FP390 or P-flavin binding protein, and not to produce
      light. A crucial basis of this hypothesis is that almost all species of luminous
      bacteria emit light in culture media containing over 2% NaCl. However, Vibrio
      albensis (Vibrio cholerae biovar albensis) NCIMB 41 emits light in freshwater and
      this appears to be in direct conflict with our hypothesis. To determine why this
      exceptional freshwater bioluminescence is emitted, we studied the lux operon and
      the regulatory system of the operon in this strain, and found that expression of
      the operon is regulated by a system involving a derivative of 4,5-dihydroxy 2,3
      pentanedione, DPD, as an inducer, and the repressor gene for the lux operon,
      luxO, is damaged by deletion of two nucleotides. Furthermore, to study the effect
      of damage to the luxO gene, pUC18 derivatives containing the damaged and repaired
      luxO sequences were prepared. Cells transfected with the damaged luxO sequence
      emitted light like the parental strain, whereas ones transfected with the
      repaired one did so only sparingly. Here we show that the light emission in
      freshwater by this strain is not in conflict with our hypothesis.

PMID- 16567413
TI  - Identification of the substrate interaction region of the chitin-binding domain
      of Streptomyces griseus chitinase C.
AB  - Chitinase C from Streptomyces griseus HUT6037 was discovered as the first
      bacterial chitinase in family 19 other than chitinases found in higher plants.
      Chitinase C comprises two domains: a chitin-binding domain (ChBD(ChiC)) for
      attachment to chitin and a chitin-catalytic domain for digesting chitin. The
      structure of ChBD(ChiC) was determined by means of 13C-, 15N-, and 1H-resonance
      nuclear magnetic resonance (NMR) spectroscopy. The conformation of its backbone
      comprised two beta-sheets composed of two and three antiparallel beta-strands,
      respectively, this being very similar to the backbone conformations of the
      cellulose-binding domain of endoglucanase Z from Erwinia chrysanthemi (CBD(EGZ))
      and the chitin-binding domain of chitinase A1 from Bacillus circulans WL-12
      (ChBD(ChiA1)). The interaction between ChBD(ChiC) and hexa-N-acetyl-chitohexaose
      was monitored through chemical shift perturbations, which showed that ChBD(ChiC)
      interacted with the substrate through two aromatic rings exposed to the solvent
      as CBD(EGZ) interacts with cellulose through three characteristic aromatic rings.
      Comparison of the conformations of ChBD(ChiA1), ChBD(ChiC), and other typical
      chitin- and cellulose-binding domains, which have three solvent-exposed aromatic
      residues responsible for binding to polysaccharides, has suggested that they have
      adopted versatile binding site conformations depending on the substrates, with
      almost the same backbone conformations being retained.

PMID- 16567414
TI  - Tannic acid, a potent inhibitor of epidermal growth factor receptor tyrosine
      kinase.
AB  - Increasing evidence supports the hypothesis that tannic acid, a plant polyphenol,
      exerts anticarcinogenic activity in chemically induced cancers. In the present
      study, tannic acid was found to strongly inhibit tyrosine kinase activity of
      epidermal growth factor receptor (EGFr) in vitro (IC50 = 323 nM). In contrast,
      the inhibition by tannic acid of p60(c-src) tyrosine kinase (IC50 = 14 microM)
      and insulin receptor tyrosine kinase (IC50 = 5 microM) was much weaker. The
      inhibition of EGFr tyrosine kinase by tannic acid was competitive with respect to
      ATP and non-competitive with respect to peptide substrate. In cultured cells,
      growth factor-induced tyrosine phosphorylation of growth factor receptors,
      including EGFr, platelet-derived growth factor receptor, and basic fibroblast
      growth factor receptor, was inhibited by tannic acid. No inhibition of insulin
      induced tyrosine phosphorylation of insulin receptor and insulin-receptor
      substrate-1 was observed. EGF-stimulated growth of HepG2 cells was inhibited in
      the presence of tannic acid. The inhibition of serine/threonine-specific protein
      kinases, including cAMP-dependent protein kinase, protein kinase C and mitogen
      activated protein kinase, by tannic acid was only detected at relatively high
      concentration, IC50 being 3, 325 and 142 microM respectively. The molecular
      modeling study suggested that tannic acid could be docked into the ATP binding
      pockets of either EGFr or insulin receptor. These results demonstrate that tannic
      acid is an in vitro potent inhibitor of EGFr tyrosine kinase.

PMID- 16567415
TI  - Distinct DNA methylation activity of Dnmt3a and Dnmt3b towards naked and
      nucleosomal DNA.
AB  - In mammals, the resetting of DNA methylation patterns in early embryos and germ
      cells is crucial for development. De novo type DNA methyltransferases Dnmt3a and
      Dnmt3b are responsible for creating DNA methylation patterns during embryogenesis
      and in germ cells. Although their in vitro DNA methylation properties are
      similar, Dnmt3a and Dnmt3b methylate different genomic DNA regions in vivo. In
      the present study, we have examined the DNA methylation activity of Dnmt3a and
      Dnmt3b towards nucleosomes reconstituted from recombinant histones and DNAs, and
      compared it to that of the corresponding naked DNAs. Dnmt3a showed higher DNA
      methylation activity than Dnmt3b towards naked DNA and the naked part of
      nucleosomal DNA. On the other hand, Dnmt3a scarcely methylated the DNA within the
      nucleosome core region, while Dnmt3b significantly did, although the activity was
      low. We propose that the preferential DNA methylation activity of Dnmt3a towards
      the naked part of nucleosomal DNA and the significant methylation activity of
      Dnmt3b towards the nucleosome core region contribute to their distinct
      methylation of genomic DNA in vivo.

PMID- 16567416
TI  - Cleavage of amyloid-beta precursor protein (APP) by membrane-type matrix
      metalloproteinases.
AB  - Amyloid-beta precursor protein (APP) was identified on expression cloning from a
      human placenta cDNA library as a gene product that modulates the activity of
      membrane-type matrix metalloproteinase-1 (MT1-MMP). Co-expression of MT1-MMP with
      APP in HEK293T cells induced cleavage and shedding of the APP ectodomain when co
      expressed with APP adaptor protein Fe65. Among the MT-MMPs tested, MT3-MMP and
      MT5-MMP also caused efficient APP shedding. The recombinant APP protein was
      cleaved by MT3-MMP in vitro at the A463-M464, N579-M580, H622-S623, and H685-Q686
      peptide bonds, which included a cleavage site within the amyloid beta peptide
      region known to produce a C-terminal fragment. The Swedish-type mutant of APP,
      which produces a high level of amyloid beta peptide, was more effectively cleaved
      by MT3-MMP than wild-type APP in both the presence and absence of Fe65; however,
      amyloid beta peptide production was not affected by MT3-MMP expression.
      Expression of MT3-MMP enhanced Fe65-dependent transactivation by APP fused to the
      Gal4 DNA-binding and transactivation domains. These results suggest that MT1-MMP,
      MT3-MMP and MT5-MMP should play an important role in the regulation of APP
      functions in tissues including the central nervous system.

PMID- 16567417
TI  - Binding of steroidogenic factor-1 to the regulatory region might not be critical
      for transcriptional regulation of the human CYP1B1 gene.
AB  - Cytochrome P450 (CYP) 1B1, which catalyzes 17beta-estradiol 4-hydroxylation, is
      expressed in steroid-related tissues including ovary, testis, and adrenal gland.
      Generally, the expressions of steroidogenic CYPs are transcriptionally regulated
      by steroidogenic factor-1 (SF-1) and cAMP response element (CRE) binding protein
      (CREB). In the present study, we examined the possibility that the human CYP1B1
      gene might be regulated by SF-1 and CREB. Gel shift analyses revealed that in
      vitro translated SF-1 can bind to the putative SF-1 binding sites, SF-1a (at 
      1722) and SF-1b (at -2474), on the CYP1B1 gene. In vitro translated CREB barely
      binds to the putative SF-1 binding sites. Luciferase analysis revealed that a
      reporter plasmid, pGL3 (-2623/+25), containing the SF-1a and SF-1b elements is
      transactivated by the concomitant co-expression of SF-1 and protein kinase A
      (PKA). However, the transcriptional activity is induced by PKA alone. Mutations
      in the SF-1a and SF-1b elements did not affect the luciferase activity. Thus, the
      binding of SF-1 to the putative SF-1 binding sites of the human CYP1B1 gene might
      not be essential for transcriptional regulation. Interestingly, deletion and
      mutation analyses indicated that the PKA signaling pathway is involved in the
      xenobiotic responsive element (XRE)-mediated transactivation of the human CYP1B1
      gene.

PMID- 16567418
TI  - Acceptor specificity of 4-alpha-glucanotransferases of mammalian glycogen
      debranching enzymes.
AB  - Glycogen debranching enzyme (GDE) has two distinct active sites for its 4-alpha
      glucanotransferase and amylo-alpha-1,6-glucosidase activities. The GDE 4-alpha
      glucanotransferases of mammals show stringent donor specificity; only alpha
      glucans with an alpha-1,6-linked maltotetraosyl or maltotriosyl branch function
      as donors of a maltotriosyl or maltosyl residue. In this study, we investigated
      the acceptor specificity of the 4-alpha-glucanotransferases using methyl alpha
      maltooligosides, p-nitrophenyl alpha-maltooligosides, and pyridylaminated
      maltooligosaccharides of various sizes as the acceptor substrates, and
      phosphorylase limit dextrin as the donor substrate. High-performance liquid
      chromatography analysis of the transfer products indicated that maltotriosyl and
      maltosyl residues were specifically transferred from phosphorylase limit dextrin
      to acceptors with a maltopentaosyl residue comprising a nonreducing-end. These
      results suggest that the acceptor binding sites in the active sites of mammalian
      GDE 4-alpha-glucanotransferases are composed of tandem subsites that are
      geometrically complementary to five glucose residues.

PMID- 16567419
TI  - 5-Oxo-eicosatetraenoic acid-induced chemotaxis: identification of a responsible
      receptor hGPCR48 and negative regulation by G protein G(12/13).
AB  - While screening genes encoding G protein-coupled receptors (GPCRs) in the human
      genome, we and other groups have identified a GPCR named hGPCR48 as a high
      affinity receptor for 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is
      arachidonic acid metabolite and an endogenous chemoattractant for granulocytes.
      Using Chinese hamster ovary (CHO) cells stably expressing hGPCR48, we show here
      that activation of the receptor causes the chemotaxis of the cells toward 5-oxo
      ETE. We also show that the chemotaxis of human granulocytes toward 5-oxo-ETE is
      inhibited by pretreatment with anti-hGPCR48 antibodies, indicating that hGPCR48
      is an endogenous receptor responsible for chemotaxis of granulocytes toward 5-oxo
      ETE. In addition, we show that the chemotaxis of CHO cells expressing hGPCR48 is
      suppressed by pretreatment with pertussis toxin, and enhanced by overexpression
      of the carboxy terminal peptides of Galpha (12/13) subunits or a regulator of the
      G protein signaling domain of p115RhoGEF, both of which are known to suppress
      G(12/13)-dependent signaling pathways. These results indicate that hGPCR48
      couples with G(i/o) and G(12/13) proteins, which then initiate or attenuate the
      chemotaxis of the cells toward 5-oxo-ETE, respectively.

PMID- 16567420
TI  - Kinetic isotope effect of the L-phenylalanine oxidase from Pseudomonas sp. P-501.
AB  - Pseudomonas L-phenylalanine oxidase (deaminating and decarboxylating) mainly
      catalyzes oxygenation when L-phenylalanine is used as the substrate, but
      oxidation when L-methionine is used as the substrate. Using [C(alpha)-H]-DL
      methionine and [C(alpha)-D]-DL-methionine as substrate, the reductive half
      reaction of FAD cofactor of enzyme has been studied by stopped-flow
      spectrophotometry. The rate of reduction of FAD cofactor has a kinetic isotope
      effect (KIE) of 5.4 and 4.1 in the absence and presence of 30% glycerol,
      respectively. The KIE is independent of temperature, but the rates of the
      reductive half reaction are dependent on temperature, indicating that thermally
      induced motion at the active site drives the H-transfer reaction by H-tunneling.

PMID- 16567421
TI  - Experimental basis for a stable plasmid, pLS30, to shuttle between Bacillus
      subtilis species by conjugational transfer.
AB  - The use of Bacillus subtilis 168 as the initial host for molecular cloning and
      subsequent delivery of the engineered DNA to other Bacillus hosts appears
      attractive, and would lead to an efficient DNA manipulation system. However,
      methods of delivery to other Bacillus species are limited due to their inability
      to develop natural competence. An alternative, unexplored conjugational transfer
      method drew our attention and a B. subtilis native plasmid, pLS30, isolated from
      B. subtilis (natto) strain IAM1168 was characterized for this aim. The nucleotide
      sequence (6,610 bp) contained the mob gene and its recognition sequence, oriT,
      that features pLS30 as a mobile plasmid between Bacillus species on conjugational
      transfer. Plasmid pLS3001, a chimera with a pBR322-based plasmid prepared in
      Escherichia coli to confer an antibiotic resistance marker, showed apparent
      mobilizing activity in the pLS20-mediated conjugational transfer system recently
      established. The rep gene and associated palT1-like sequence common to all other
      pLS plasmids previously sequenced indicated that pLS30 is a typical rolling
      circle replicating (RCR) type plasmid. Due to the significant stability of pLS30
      in IAM1168, application of a mobile plasmid would allow quick propagation to
      Bacillus species.

PMID- 16567422
TI  - Peroxisome proliferator-activated receptor subtypes differentially cooperate with
      other transcription factors in selective transactivation of the perilipin/PEX11
      alpha gene pair.
AB  - Perilipin is an adipocyte-specific protein associated with lipid droplets that is
      crucial for the regulation of storage and mobilization of lipids. We earlier
      reported that the mouse perilipin gene is regulated by peroxisome proliferator
      activated receptor (PPAR) gamma through a peroxisome proliferator-response
      element (PPRE) positioned upstream of the perilipin promoter. Moreover, we showed
      that this PPRE also controls expression of the PEX11alpha gene, which is located
      further upstream. We show here that three elements, A, B, and C, in close
      proximity downstream of the PPRE, are essential for transactivation of the
      perilipin gene by PPARgamma. Electrophoretic gel-mobility shift assays
      demonstrated that nuclear factor (NF)-1 subtypes bind specifically to element B.
      Furthermore, chromatin immunoprecipitation using 3T3-L1 cells revealed that NF-1A
      and NF-1B bind to element B in a differentiation-dependent fashion, whereas
      binding is constitutive with NF-1C and NF-1X. Element C is likely to be a binding
      motif for nuclear receptors. With PPARalpha, elements A-C do not appear to be
      required for transactivation of the PEX11alpha gene, so that cooperation with
      other transcription factors may be differentially involved in selective
      transactivation of the PEX11alpha and perilipin genes by different PPAR subtypes.

PMID- 16567423
TI  - Roles of adjoining Asp and Cys residues of first matrix-facing loop in transport
      activity of yeast and bovine mitochondrial ADP/ATP carriers.
AB  - The mitochondrial ADP/ATP carrier (AAC) transports substrate by interconversion
      of its conformation between m- and c-states. The 1st loop facing the matrix (LM1)
      is extruded into the matrix in the m-state and is suggested to intrude into the
      mitochondrial membrane on conversion to the c-state conformation [Hashimoto, M.,
      Majima, E., Goto, S., Shinohara, Y., and Terada, H. (1999) Biochemistry 38, 1050
      1056]. To elucidate the mechanism of the translocation of LM1, we examined the
      effects of site-directed mutagenesis of two adjoining residues, Cys56 and Asp55
      in the bovine type 1 AAC and Cys73 and Asp72 in the yeast type 2 AAC, on the
      substrate transport activity. We found that (i) replacement of the Cys by bulky
      and hydrophilic residues was unfavorable for efficient transport activity, (ii)
      the carboxyl groups of the Asp residues of the bovine and yeast AACs were
      essential and strictly position-specific, and (iii) hence, the mutation to Glu
      showed transport activity comparable to that of the native AACs. Based on these
      results, we discussed the functional role of LM1 in the transport activity of
      AAC.

PMID- 16567424
TI  - Pepstatin A, an aspartic proteinase inhibitor, suppresses RANKL-induced
      osteoclast differentiation.
AB  - Pepstatin A is well known to be an inhibitor of aspartic proteinases such as
      pepsin, cathepsins D and E. Except for its role as a proteinase inhibitor,
      however, the pharmacological action of pepstatin A upon cells remain unclear. In
      this study, we found that pepstatin A suppressed receptor activator of NF-kappaB
      ligand (RANKL)-induced osteoclast differentiation. Pepstatin A suppressed the
      formation of multinuclear osteoclasts dose-dependently. This inhibition of the
      formation only affected osteoclast cells, i.e., not osteoblast-like cells.
      Furthermore, pepstatin A also suppressed differentiation from pre-osteoclast
      cells to mononuclear osteoclast cells dose-dependently. This inhibition seems to
      be independent of the activities of proteinases such as cathepsin D, because the
      formation of osteoclasts was not suppressed with the concentration that inhibited
      the activity of cathepsin D. Cell signaling analysis indicated that the
      phosphorylation of ERK was inhibited in pepstatin A-treated cells, while the
      phosphorylation of IkappaB and Akt showed almost no change. Furthermore,
      pepstatin A decreased the expression of nuclear factor of activated T cells c1
      (NFATc1). These results suggest that pepstatin A suppresses the differentiation
      of osteoclasts through the blockade of ERK signaling and the inhibition of NFATc1
      expression.

PMID- 16567425
TI  - Catalytic promiscuity in dihydroxy-acid dehydratase from the thermoacidophilic
      archaeon Sulfolobus solfataricus.
AB  - Dihydroxy-acid dehydratase (DHAD) is one of the key enzymes involved in the
      biosynthetic pathway of the branched chain amino acids. Although the enzyme has
      been purified and characterized in various mesophiles, including bacteria and
      eukarya, the biochemical properties of DHAD from hyperthermophilic archaea have
      not yet been reported. In this study we cloned, expressed in Escherichia coli,
      and purified a DHAD homologue from the thermoacidophilic archaeon Sulfolobus
      solfataricus, which grows optimally at 80 degrees C and pH 3. The recombinant S.
      solfataricus DHAD (rSso_DHAD) showed the highest activity on 2,3
      dihydroxyisovalerate among 17 aldonic acids tested. Interestingly, this enzyme
      also displayed high activity toward d-gluconate and some other pentonic and
      hexonic sugar acids. The k(cat)/K(m) values were 140.3 mM(-1) s(-1) for 2,3
      dihydroxyisovalerate and 20.0 mM(-1) s(-1) for d-gluconate, respectively. A
      possible evolutionary explanation for substrate promiscuity was provided through
      amino acid sequence alignments of DHADs and 6-phosphogluconate dehydratases from
      archaea, bacteria and eukarya.

PMID- 16567426
TI  - Saccharomyces cerevisiae Rot1p is an ER-localized membrane protein that may
      function with BiP/Kar2p in protein folding.
AB  - The 70-kDa heat shock protein (Hsp70) family of molecular chaperones cooperates
      with cofactors to promote protein folding, assembly of protein complexes and
      translocation of proteins across membranes. Although many cofactors of cytosolic
      Hsp70s have been identified, knowledge about cofactors of BiP/Kar2p, an
      endoplasmic reticulum (ER)-resident Hsp70, is still poor. Here we propose the
      Saccharomyces cerevisiae protein Rot1p as a possible cofactor of BiP/Kar2p
      involved in protein folding. Rot1p was found to be an essential, ER-localized
      membrane protein facing the lumen. ROT1 genetically interacted with several ER
      chaperone genes including KAR2, and the rot1-2 mutation triggered the unfolded
      protein response. Rot1p associated with Kar2p, especially under conditions of ER
      stress, and maturation of a model protein, a reduced form of carboxypeptidaseY,
      was impaired in a kar2-1 rot1-2 double mutant. These findings suggest that Rot1p
      participates in protein folding with Kar2p. Morphological analysis of rot1-2
      cells revealed cell wall defects and accumulation of autophagic bodies in the
      vacuole. This implies that the protein folding machinery in which Rot1p is
      involved chaperones proteins acting in various physiological processes including
      cell wall synthesis and lysis of autophagic bodies.

PMID- 16567427
TI  - Identification and characterization of carbohydrate molecules in mammalian cells
      recognized by dengue virus type 2.
AB  - The interaction between cell surface receptors and the envelope glycoprotein
      (EGP) on the viral membrane surface is the initial step of Dengue virus
      infection. To understand the host range, tissue tropism, and virulence of this
      pathogen, it is critical to elucidate the molecular mechanisms of the interaction
      of EGP with receptor molecules. Here, using a TLC/virus-binding assay, we
      isolated and characterized a carbohydrate molecule on mammalian cell surfaces
      that is recognized by dengue virus type 2 (DEN2). Structural determination by
      immunochemical methods showed that the carbohydrate structure of the purified
      glycosphingolipid was neolactotetraosylceramide (nLc4Cer). This glycosphingolipid
      was expressed on the cell surface of susceptible cells, such as human
      erythroleukemia K562 and baby hamster kidney BHK-21. All serotypes of DEN
      viruses, DEN1 to DEN4, reacted with nLc4Cer, and the non-reducing terminal
      disaccharide residue Galbeta1-4GlcNAcbeta1- was found to be a critical
      determinant for the binding of DEN2. Chemically synthesized derivatives carrying
      multiple carbohydrate residues of nLc4, but not nLc4 oligosaccharide, inhibited
      DEN2 infection of BHK-21 cells. These findings strongly suggested that
      multivalent nLc4 oligosaccharide could act as a competitive inhibitor against the
      binding of DEN2 to the host cells.

PMID- 16567429
TI  - As technology evolves, so should its application: shortcomings of the "18-week
      anatomy scan".

PMID- 16567428
TI  - Thiolysis of poly(3-hydroxybutyrate) with polyhydroxyalkanoate synthase from
      Ralstonia eutropha.
AB  - Poly(3-hydroxybutyrate) (PHB) is synthesized from 3-hydroxybutyryl-CoA by
      polyhydroxyalkanoate synthase and hydrolyzed by PHB depolymerase. In this study,
      we focused on the reverse reaction of polyhydroxyalkanoate synthase, and propose
      the possibility that PHB can be degraded through a novel process, that is
      thiolysis of PHB with CoASH. Polyhydroxyalkanoate synthase of Ralstonia eutropha
      was incubated with 14C-labeled PHB and CoASH. The reaction mixture was
      fractionated by HPLC and then analyzed with a scintillation counter. The analysis
      revealed 3-hydroxybutyryl-CoA to be a product of the reaction. When NADP+ and
      acetoacetyl-CoA reductase were added to the reaction mixture, an increase in
      absorbance at 340 nm was observed. Native PHB inclusion bodies from R. eutropha
      also showed thiolytic activity. This is the first indication that
      polyhydroxyalkanoate synthase catalyzes both the synthesis and degradation of
      PHB, and that native PHB inclusion bodies has thiolytic activity.

PMID- 16567430
TI  - Prenatal diagnosis of trisomy 13: analysis of 28 cases.
AB  - OBJECTIVE: The purpose of this study was to investigate the role of second
      trimester sonographic examination in the prenatal diagnosis of trisomy 13.
      METHODS: Of 22,150 fetal chromosome analyses, 28 fetuses with trisomy 13 were
      found between 1990 and 2004. Sonographic findings of this aneuploidy were
      analyzed in this study. RESULTS: The average maternal age was 32.4 years; the
      average gestational age was 19.5 weeks. There was an 89.3% (n = 25) total
      prevalence of sonographic abnormalities in fetuses with trisomy 13 in this
      series. Major (structural) malformations were seen in 23 cases (82.1%), whereas
      minor anomalies were detected on sonography in 16 cases (57.1%). Although in 2
      fetuses 1 minor anomaly was the only sonographic sign of trisomy 13, other cases
      with minor anomalies (87.5% [n = 14]) were multiplex malformations, in which
      combinations of major and minor anomalies were detected on sonography. The most
      frequently seen structural abnormalities were central nervous system and facial
      anomalies (64.3% [n = 18]). Among central nervous system anomalies,
      ventriculomegaly and holoprosencephaly were seen most frequently. Cardiovascular
      anomalies were detected in 53.6% (n = 15) of the fetuses with trisomy 13. This
      high frequency underlines the importance of echocardiography in diagnosing this
      aneuploidy. Among minor anomalies, increased nuchal translucency (21.4%) and
      echogenic bowel (17.9%) were the most common findings. CONCLUSIONS: Second
      trimester sonographic examination is capable of showing anomalies that are
      characteristic of trisomy 13; thus, the scan can indicate whether fetal
      karyotyping is advisable. Incorporation of careful assessment of the fetal
      cardiovascular system by sonography certainly increases the detection rate of
      trisomy 13.

PMID- 16567431
TI  - Evaluating the efficiency of using second-trimester nasal bone hypoplasia as a
      single or a combined marker for fetal aneuploidy.
AB  - OBJECTIVE: Although second-trimester nasal bone (NB) hypoplasia has been
      associated with fetal aneuploidy, its role as a single marker is still uncertain.
      Our objective was to evaluate the efficiency of NB hypoplasia as an independent
      marker for fetal aneuploidy. METHODS: This was a prospective cohort study of
      women undergoing an anatomic survey between 16 and 22 weeks' gestation. The fetal
      NB and other markers of fetal aneuploidy, including nuchal fold, femur and
      humeral lengths, choroid plexus cysts, major fetal anomalies, echogenic bowel,
      pyelectasis, and hypoplastic fifth digits, were evaluated. Nasal bone hypoplasia
      was defined either as an absent NB or by a ratio of the biparietal diameter to
      NB. Fetuses or infants with fetal aneuploidy were compared with those without for
      the presence of NB hypoplasia either as a single marker or in the presence of
      other markers for aneuploidy. RESULTS: Of 2885 women evaluated, NB measurements
      were obtained in 2465 (85%). There were 35 (1.4%) cases with fetal aneuploidy.
      The sensitivity and specificity of a single NB in detecting Down syndrome varied
      from 23% to 64% and 57% to 99%, respectively, depending on the definition of NB
      hypoplasia used. There was an improvement in the efficiency of using the NB when
      combined with other markers, with sensitivity and specificity increasing from 59%
      to 82% and 74% to 87%, respectively. CONCLUSIONS: Nasal bone hypoplasia is a
      marker for fetal aneuploidy. The combination of the NB with other makers was
      associated with an improvement in detection of fetal aneuploidy.

PMID- 16567432
TI  - The effects of maternal position on the amniotic fluid index.
AB  - OBJECTIVE: We investigated the influence of maternal positioning on the
      measurement of the amniotic fluid index (AFI) in third-trimester pregnancies. We
      wanted to determine whether a change in the position of the women, from supine
      flat to supine-elevated, would influence the measurement of the AFI. METHODS:
      Each patient had AFI measurements obtained in both positions by the same
      investigator. RESULTS: We determined the values of the amniotic fluid index to be
      consistent in both positions for pregnancies with normal AFI measurements.
      CONCLUSIONS: Measurements of the amniotic fluid did not appear to be influenced
      by maternal position in the third trimester when the AFI was in the normal range.

PMID- 16567433
TI  - Instability of Doppler cerebral blood flow in monochorionic twins.
AB  - OBJECTIVE: The purpose of this study was to evaluate Doppler flow velocity
      changes in cerebral vessels of monochorionic twins with twin-twin transfusion
      syndrome (TTTS). METHODS: Repeated Doppler umbilical and cerebral blood flow
      studies were performed in 7 twin pairs with TTTS. Eight monochorionic twin pairs
      and 11 dichorionic twin pairs served as control groups. The following Doppler
      parameters were assessed: umbilical artery pulsatility index (PI), middle
      cerebral artery (MCA) PI, cerebroplacental ratio, delta PI between the umbilical
      artery and MCA, and peak systolic velocity (PSV) in the MCA. RESULTS: Significant
      variations in PSV in the MCA and cerebral indices were found in the study group
      of monochorionic twins with TTTS. Periods of high PSV with low PI in the MCA were
      followed by lower PSV in the same fetus. Repeated measurements in the comparison
      groups were stable without significant variations. The delta cerebroplacental
      ratio was significantly higher in the study group (0.38 versus 0.09 and 0.19 in
      the comparison groups; P < .02). CONCLUSIONS: Significant changes in Doppler flow
      velocity and indices suggest instability of cerebral blood flow with episodes of
      "hyperperfusion" in monochorionic twins with TTTS. Further studies are needed to
      elucidate the relationship of these transient changes to neurologic sequelae in
      the neonate.

PMID- 16567434
TI  - Fetal echocardiographic findings are not predictive of death in twin-twin
      transfusion syndrome.
AB  - OBJECTIVE: The purpose of this study was to determine whether fetal
      echocardiographic findings are predictive of prognosis in recipient fetuses with
      twin-twin transfusion syndrome (TTTS). METHODS: A cohort of 30 pregnancies with
      TTTS between 1990 and 2001 was included. Diagnosis and staging of TTTS were made
      according to the Quintero system. Fetal echocardiographic findings of
      cardiomegaly, right ventricular hypertrophy, and tricuspid regurgitation were
      evaluated for relationship with fetal death. Power analysis revealed an
      approximately 80% power to detect a 2-fold increased risk of fetal death, with
      alpha = .05. Logistic regression was used to determine the relationship between
      echocardiographic findings and death. RESULTS: Most pregnancies were Quintero
      stage 1, n = 13 (43%), and ranged in severity to Quintero stage 5, n = 4 (13%).
      Cardiac findings in the recipient fetus that were assessed for a relationship
      with death included cardiomegaly at the initial appearance of TTTS or at the most
      severe evaluation findings, right ventricular hypertrophy at initial appearance
      or at the most severe evaluation findings, or tricuspid regurgitation at initial
      appearance or at the most severe evaluation findings. Fetal or neonatal death in
      the recipient twin was not related to the presence of cardiac findings (odds
      ratio, 0.77; 95% confidence interval, 0.16-3.74). CONCLUSIONS: Fetal
      echocardiographic findings, whether evaluated at initial appearance or over the
      course of serial evaluations, were not related to fetal or neonatal death in
      recipient twins with TTTS.

PMID- 16567435
TI  - Evaluation of the agreement between 3-dimensional ultrasonography and magnetic
      resonance imaging for fetal lung volume measurement.
AB  - OBJECTIVE: The purpose of this study was to assess the agreement between 3
      dimensional ultrasonography (3DUS) and magnetic resonance imaging (MRI) for lung
      volumetry in fetuses with and without abnormalities associated with lung
      hypoplasia. METHODS: Fifty-nine singleton pregnancies were evaluated. Cases were
      separated into groups 1 and 2, according to the presence or absence of
      malformations associated with lung hypoplasia, respectively. Fetal lung volume
      was calculated by the Virtual Organ Computer-Aided Analysis (VOCAL) program of
      the 3DUS and the MRI. In both groups, measurements performed with all VOCAL
      angles were compared among themselves and with those obtained by MRI. Bland
      Altman tests and analysis of variance were used for this purpose. RESULTS: In
      groups 1 and 2, the mean lung volume obtained with each rotation angle of the
      VOCAL technique was significantly smaller than the mean volume calculated by MRI
      (P < .001), and the mean volume obtained with the 30 degrees rotation step was
      significantly smaller than those obtained with the other rotation steps of the
      VOCAL technique. Bland-Altman tests confirmed this underestimation and showed a
      broad 95% confidence interval when the VOCAL angles were compared with those of
      MRI and when the 30 degrees rotation step was compared with the other VOCAL
      steps. CONCLUSIONS: There was a substantial discrepancy between 3DUS and MRI and
      between the 30 degrees rotation step of the VOCAL technique and the other
      rotation angles, for lung volume measurement in fetuses with and without
      abnormalities associated with lung hypoplasia.

PMID- 16567436
TI  - Changes in the sonographic appearance of the uterus after discontinuation of
      tamoxifen therapy.
AB  - OBJECTIVE: The purpose of this study was to assess the duration of
      sonographically detected changes in the endometrium of women with a history of
      tamoxifen use. METHODS: Patients with breast cancer who had a history of
      tamoxifen use and documented pelvic sonographic studies were identified by means
      of clinic databases in both the Section of Gynecological Oncology and the Section
      of Obstetrical and Gynecological Ultrasound, University of Chicago, between
      January 1, 1996, and March 30, 2004. Of the 99 patients who met study criteria,
      34 had discontinued tamoxifen use before the sonographic evaluation. Each
      patient's age, gravity and parity, weight, ethnicity, duration and dose of drug
      use, interval from drug discontinuation until sonographic evaluation, and uterine
      pathologic findings were reviewed. Endometrial thickness as assessed by pelvic
      sonography was examined in relation to duration of tamoxifen use and time from
      discontinuation of the drug. Statistical analysis was performed with linear
      regression and mixed effect linear regression models. RESULTS: Endometrial
      thickness increased with increasing duration of tamoxifen use at a rate of 0.75
      mm/y. The mean endometrial thickness after approximately 5 years of tamoxifen use
      was 12 mm (range, 6-21 mm). After discontinuation of tamoxifen, endometrial
      thickness decreased by 1.27 mm/y. CONCLUSIONS: Endometrial thickness as measured
      by pelvic ultrasound examination increases with the duration of tamoxifen use.
      After discontinuation of the drug, the measured thickness decreases but at a very
      slow rate.

PMID- 16567437
TI  - Assessment of the therapeutic response of hepatocellular carcinoma treated with
      transcatheter arterial chemoembolization: comparison of contrast-enhanced
      sonography and 3-phase computed tomography.
AB  - OBJECTIVE: The purpose of this study was to compare contrast-enhanced sonography
      with 3-phase computed tomography (CT) in assessing the therapeutic response of
      hepatocellular carcinomas (HCCs) treated with transcatheter arterial
      chemoembolization (TACE). METHODS: Twenty-nine nodular HCCs treated with TACE
      were examined with contrast-enhanced sonography, 3-phase helical CT, and
      conventional angiography. Contrast-enhanced sonographic and CT findings were
      interpreted separately and prospectively for the presence or absence of contrast
      enhancement in the treated HCCs. Conventional angiography served as the reference
      standard. RESULTS: Intratumoral enhancement was seen in 19 HCCs (61%) on contrast
      enhanced sonography and 12 HCCs (39%) on CT. Enhancement patterns on sonography
      were blush in 8 (42%), branching in 2 (11%), nodular in 4 (21%), and stippled in
      5 (26%). Of the 19 HCCs with intratumoral enhancement on contrast-enhanced
      sonography, 13 (68%) showed tumor staining on angiography. Of the 12 HCCs without
      intratumoral enhancement on sonography, 1 (8%) showed tumor staining on
      angiography. The sensitivity and specificity of contrast-enhanced sonography in
      depicting flow in HCCs treated with TACE were 93% and 65%, respectively. The
      sensitivity and specificity of 3-phase CT were 64% and 100%. CONCLUSIONS:
      Contrast-enhanced sonography is a more sensitive imaging method than 3-phase CT
      in depicting vascularity in HCCs treated with TACE.

PMID- 16567438
TI  - Correlation between estimates of tumor perfusion from microbubble contrast
      enhanced sonography and dynamic contrast-enhanced magnetic resonance imaging.
AB  - OBJECTIVE: We compared measurements of tumor perfusion from microbubble contrast
      enhanced sonography (MCES) and dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) in an animal tumor model. METHODS: Seven mice were implanted
      with Lewis lung carcinoma cells on their hind limbs and imaged 14 days later with
      a Philips 5- to 7-MHz sonography system (Philips Medical Systems, Andover, MA)
      and a Varian 7.0-T MRI system (Varian, Inc, Palo Alto, CA). For sonographic
      imaging 100 microL of a perfluoropropane microbubble contrast agent (Definity;
      Bristol-Myers Squibb Medical Imaging, Billerica, MA) was injected and allowed to
      reach a pseudo steady state, after which a high-mechanical index pulse was
      delivered to destroy the microbubbles within the field of view, and the
      replenishment of the microbubbles was imaged for 30 to 60 seconds. The MRI
      included acquisition of a T(10) map and 35 serial T(1)-weighted images
      (repetition time, 100 milliseconds; echo time, 3.1 milliseconds; alpha, 30
      degrees ) after the injection of 100 microL of 0.2-mmol/kg gadopentetate
      dimeglumine (Magnevist; Berlex, Wayne, NJ). Region-of-interest and voxel-by-voxel
      analyses of both data sets were performed; microbubble contrast-enhanced
      sonography returned estimates of microvessel cross-sectional area, microbubble
      velocity, and mean blood flow, whereas DCE-MRI returned estimates of a perfusion
      permeability index and the extravascular extracellular volume fraction. RESULTS:
      Comparing similar regions of tumor tissue seen on sonography and MRI, region-of
      interest analyses revealed a strong (r(2) = 0.57) and significant relationship (P
      < .002) between the estimates of perfusion obtained by the two modalities.
      CONCLUSIONS: Microbubble contrast-enhanced sonography can effectively depict
      intratumoral heterogeneity in preclinical xenograft models when voxel-by-voxel
      analysis is performed, and this analysis correlates with similar DCE-MRI
      measurements.

PMID- 16567439
TI  - Transcranial contrast imaging of cerebral perfusion in patients with space
      occupying intracranial lesions.
AB  - OBJECTIVE: The aim of this study was to evaluate a deficit in cerebral perfusion
      after administration of the contrast agent SonoVue (Bracco Altana Pharma,
      Konstanz, Germany) in patients with intracranial space-occupying lesions.
      METHODS: We used transcranial duplex sonography to examine 10 healthy volunteers
      and 4 patients. Of the patients, one 55-year-old woman had an intracranial
      glioblastoma; one 54-year-old woman had an intracranial hemorrhage; and one 49
      year-old woman and one 69-year-old man had a malignant middle cerebral artery
      infarction. A decompressive craniectomy was performed in the 2 patients with
      malignant middle cerebral artery infarction. Triggered images with pulsing
      intervals of 1000 milliseconds were used for the evaluation of time-intensity
      curves in several regions of interest. The mechanical index was set at 1.6; in
      patients with a craniectomy, the mechanical index was set at 1.1. RESULTS: In all
      patients, the perfusion deficit could be recognized in the ipsilateral
      hemisphere. The superimposition of the sonographic images with those from
      computed tomography or magnetic resonance imaging showed a good correspondence in
      shape and size in patients with a craniectomy. In patients without a craniectomy,
      a rough correspondence with findings from magnetic resonance imaging or computed
      tomography could be recognized. CONCLUSIONS: By using contrast-enhanced
      transcranial duplex sonography, it is possible to image the perfusion deficit in
      cerebral microcirculation in patients with intracranial space-occupying lesions.
      These results should be confirmed by more pathologic cases and correlated with
      magnetic resonance imaging and other neuroimaging techniques. Additionally,
      further technical development in sonographic systems is necessary to improve the
      diagnostics of cerebral perfusion deficit.

PMID- 16567441
TI  - Transvaginal sonographic findings associated with emphysematous vaginitis at 32
      weeks' gestation.

PMID- 16567440
TI  - Three-dimensional ultrasonographic reslicing of the fetal brain to assist
      prenatal diagnosis of central nervous system anomalies.
AB  - OBJECTIVES: The purpose of this study was to evaluate the potential of 3
      dimensional ultrasonographic planar and nonplanar reslicing techniques. METHODS:
      Fetuses with severe brain anomalies diagnosed by means of 2-dimensional
      ultrasonography were prospectively included in the study. Good-quality 3
      dimensional volumes of the fetal head were obtained in each case. Subsequently,
      these volumes were reviewed with use of 3-dimensional extended imaging with
      Oblique View and DynamicMR (Medison Co, Ltd, Seoul, Korea). RESULTS: Eight
      fetuses (mean gestational age, 23 weeks; range, 20-30 weeks) with the following
      central nervous system anomalies were examined: semilobar holoprosencephaly,
      absent cavum septum pellucidum, porencephaly in twin-to-twin transfusion
      syndrome, partial agenesis of the corpus callosum, Dandy-Walker variant, open-lip
      schizencephaly, aneurysm of the vein of Galen, and dilated cavum vergae.
      CONCLUSIONS: Planar and nonplanar reslicing of the volumes delivered informative
      images in any reconstructed plane. One important prerequisite, however, was the
      absence of acoustic shadowing during data acquisition.

PMID- 16567442
TI  - Prenatal sonographic diagnosis of milroy congenital lymphedema.

PMID- 16567443
TI  - Acute progression of a unilateral fetal ovarian cyst to complex bilateral cysts
      causing acute polyhydramnios.

PMID- 16567444
TI  - Prenatal diagnosis of giant fetal truncal hemangioma by means of 2- and 3
      dimensional sonography with magnetic resonance imaging.

PMID- 16567446
TI  - Prenatal diagnosis of spondylocostal dysostosis with 3-dimensional
      ultrasonography.

PMID- 16567445
TI  - Fetal fibular hemimelia: case report and review of the literature.

PMID- 16567447
TI  - Cervical varix as a cause of vaginal bleeding during pregnancy: prenatal
      diagnosis by color Doppler ultrasonography.

PMID- 16567448
TI  - Schizencephaly in a dysgenetic fetal brain: prenatal sonographic, magnetic
      resonance imaging, and postmortem correlation.

PMID- 16567449
TI  - High-resolution sonographic diagnosis of sirenomelia.

PMID- 16567450
TI  - Pattern recognition and descriptive sonographic scoring in the diagnosis of
      ovarian cancer.

PMID- 16567451
TI  - The mechanical index, ultrasound practices, and the ALARA principle.

PMID- 16567453
TI  - Low-intensity pulsed ultrasound accelerates bone-tendon junction healing: a
      partial patellectomy model in rabbits.
AB  - BACKGROUND: Low-intensity pulsed ultrasound has been demonstrated to be
      beneficial for accelerating fracture healing, delayed union, nonunion, and soft
      tissue repair. HYPOTHESIS: Low-intensity pulsed ultrasound accelerates healing of
      bone-to-tendon junction repair by promoting osteogenesis and tissue remodeling at
      the healing junction. STUDY DESIGN: Controlled laboratory study. METHODS:
      Standard partial patellectomy was conducted in forty-eight 18-week-old rabbits
      divided into an ultrasound treatment and control group. Daily ultrasound was
      delivered 3 days after surgery onto the patellar tendon-patella healing junction
      and continuously up to weeks 2, 4, 8, and 16 postoperatively, when the patella
      patellar tendon complexes were harvested for radiographic, histologic, and
      biomechanical evaluations. RESULTS: Radiographic measurements showed
      significantly more newly formed bone at the patellar tendon-patella healing
      junction in the ultrasound group compared with the controls at week 8 (4.91 +/-
      2.74 mm(2) vs 2.50 +/- 1.83 mm(2), P < .05) and week 16 (7.22 +/- 2.34 mm(2) vs
      4.61 +/- 2.22 mm(2), P < .05) after partial patellectomy. Histologically, the
      ultrasound group at weeks 8 and 16 showed improved tissue integration,
      characterized by trabecular bone expansion from the remaining patella and
      regeneration of fibrocartilage layer at the patellar tendon-patella healing
      junction. Fluorescence microscopy revealed earlier bone formation in the
      ultrasound group when compared with the controls at week 8 (1.78 +/- 0.32 vs 1.23
      +/- 0.43, P < .01) and week 16 (2.10 +/- 0.67 vs 1.29 +/- 0.35, P < .01).
      Mechanical testing showed significantly higher failure load and ultimate strength
      in the ultrasound group (300.2 +/- 61.7 N and 7.10 +/- 1.29 MPa, respectively) as
      compared with controls (222.3 +/- 65.1 N and 5.26 +/- 1.36 MPa, respectively) at
      week 16 (P < .05 for both). CONCLUSION: Low-intensity pulsed ultrasound was able
      to accelerate bone-to-tendon junction repair. CLINICAL RELEVANCE: These results
      may help establish treatment efficacy for accelerating bone-to-tendon junction
      repair and facilitating earlier rehabilitation.

PMID- 16567455
TI  - Tarsal tunnel syndrome in athletes.
AB  - BACKGROUND: The details of the occurrence of tarsal tunnel syndrome in athletes
      have not been well documented in the literature, and more data on tarsal tunnel
      syndrome related to sporting activity are necessary to enable better recognition
      of this condition. HYPOTHESIS: Sporting activities make athletes vulnerable to
      the occurrence of tarsal tunnel syndrome under specific conditions. STUDY DESIGN:
      Case series; Level of evidence, 4. METHODS: Between 1986 and 2002, 18 patients
      with tarsal tunnel syndrome related to sporting activities were surgically
      treated, of whom 15 patients (21 feet; mean age, 17.8 years) were competitive
      athletes and 3 were recreational sports amateurs (4 feet; mean age, 52.7 years).
      To assess the role of physical factors and sporting activities in making athletes
      vulnerable to the occurrence of tarsal tunnel syndrome, the authors reviewed the
      medical charts and evaluated the results of treatment. The mean duration of
      follow-up was 58.6 months. RESULTS: Activities that triggered tarsal tunnel
      syndrome were those that applied a heavy burden on the ankle joint such as
      sprinting, jumping, and performing ashibarai in judo under specific physical
      conditions. Predisposing underlying physical factors were flatfoot deformity and
      an existence of talocalcaneal coalition, accessory muscles, and bony fragments
      around the tarsal tunnel. The majority of patients were able to return to the
      same sport after treatment. CONCLUSION: Tarsal tunnel syndrome occurs in athletes
      involved in strenuous sporting activities, especially when predisposing physical
      factors are present.

PMID- 16567454
TI  - An in vivo injury model of posterolateral knee instability.
AB  - BACKGROUND: Posterolateral knee instability is a difficult clinical problem to
      diagnose and treat. To best evaluate its natural history and the effects of
      interventional treatments, it is important to develop an in vivo model in an
      attempt to validate human cadaveric and clinical observational studies. PURPOSE:
      To develop an in vivo model of posterolateral knee instability in the rabbit and
      to determine the natural history of untreated posterolateral knee injuries at 6
      months postoperatively. STUDY DESIGN: Controlled laboratory study. METHODS: The
      fibular collateral ligament and popliteus tendon were surgically transected in 1
      knee in each of 10 skeletally mature New Zealand White rabbits, with the
      contralateral knee serving as a control knee. At 6 months postoperatively, the
      rabbits were euthanized, the knees were removed, and biomechanical testing of
      knee joint stability was performed. After biomechanical testing, histological
      sections of each proximal tibia and distal femur were evaluated, and each
      proximal tibia was graded using an osteoarthritis grading scheme. RESULTS:
      Biomechanical testing revealed a statistically significant difference in amount
      of rotation in the operated knees compared with the unoperated control knees to
      varus moments at 30 degrees , 60 degrees , and 90 degrees and to external
      rotation torques at 30 degrees and 60 degrees . Morphological analysis revealed
      no significant difference in lesions of osteoarthritis in the medial compartment
      of the operated knees compared with the unoperated knees. CONCLUSIONS: Although
      the presence of posterolateral knee instability was validated 6 months after
      surgery in this model, the authors did not identify significant differences in
      lesions of osteoarthritis in the operated knees compared with the unoperated
      control knees. CLINICAL SIGNIFICANCE: This study confirms that posterolateral
      knee instability can be created in an animal model. It also recapitulates the
      clinical observation in humans that untreated posterolateral knee injuries do not
      heal. Similar to animal models of medial collateral ligament sectioning, further
      studies to validate a posterolateral instability knee model may lead to
      interventional studies to determine the best way to treat this complex knee
      instability pattern.

PMID- 16567456
TI  - Autologous osteochondral mosaicplasty for capitellar osteochondritis dissecans in
      teenaged patients.
AB  - BACKGROUND: Autologous osteochondral mosaicplasty is a new technique to provide
      hyaline repair for articular defects. Although recent studies have reported the
      successful treatment of articular defects in the knee and ankle joints with this
      surgical procedure, little attention has been given to the surgical efficacy of
      mosaicplasty in the treatment of osteochondritis dissecans of the humeral
      capitellum. PURPOSE: To clarify the clinical outcomes of mosaicplasty for
      teenaged patients with advanced lesions of capitellar osteochondritis dissecans.
      STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Eight teenaged patients
      with advanced lesions of capitellar osteochondritis dissecans underwent
      mosaicplasties. All patients were baseball players who were affected on the right
      side, which was also their throwing side. The surgical technique involves
      obtaining small-sized cylindrical osteochondral grafts from the lateral periphery
      of the femoral condyles and transplanting them to prepared osteochondral defects.
      At a mean follow-up of 24 months, all patients were evaluated clinically and
      radiographically. RESULTS: Seven of the 8 patients were free from elbow pain, and
      the remaining patient had mild pain occasionally. The mean clinical score
      described by Timmerman and Andrews (a maximum of 200 points) significantly
      improved from 140 points to 183 points postoperatively. All patients except one
      had excellent or good clinical results. Radiographically, the graft incorporation
      and a normal contour of the subchondral cortex were found in all patients.
      Magnetic resonance imaging showed that the preoperative heterogeneity of the
      lesion had disappeared and the signal intensity returned to normal. Six of the 8
      patients, including all 3 pitchers, returned to competitive-level baseball.
      CONCLUSION: Mosaicplasty for advanced lesions of capitellar osteochondritis
      dissecans in teenaged baseball players can provide satisfactory clinical and
      radiographic results.

PMID- 16567457
TI  - Osteochondritis dissecans of the entire femoral trochlea.

PMID- 16567458
TI  - Arthroscopic capsulolabral reconstruction for posterior instability of the
      shoulder: a prospective study of 100 shoulders.
AB  - BACKGROUND: There are few reports in the literature detailing arthroscopic
      treatment of unidirectional posterior shoulder instability. HYPOTHESIS:
      Arthroscopic capsulolabral reconstruction is effective in restoring stability and
      function and alleviating pain in athletes with symptomatic unidirectional
      posterior instability. This population has significant differences in glenoid and
      chondrolabral versions when compared with controls. STUDY DESIGN: Cohort study;
      Level of evidence, 2. METHODS: Ninety-one athletes (100 shoulders) with
      unidirectional recurrent posterior shoulder instability were treated with an
      arthroscopic posterior capsulolabral reconstruction and evaluated at a mean of 27
      months postoperatively. A subset of 51 shoulders in contact athletes were
      compared with the entire group of 100 shoulders. Patients were evaluated
      prospectively with the American Shoulder and Elbow Surgeons scoring system.
      Stability, strength, and range of motion were evaluated preoperatively and
      postoperatively with standardized subjective scales. Forty-eight shoulders had
      magnetic resonance arthrograms performed and were available for review. The
      posterior inferior chondrolabral and bony glenoid versions were measured and
      compared with controls. RESULTS: At a mean of 27 months postoperatively, the mean
      American Shoulder and Elbow Surgeons score improved from 50.36 to 85.66 (P <
      .001). There were significant improvements in stability, pain, and function based
      on standardized subjective scales (P < .001). The contact athletes did not
      demonstrate any significant differences when compared with the entire cohort for
      any outcome measure. The results in the 71 shoulders followed for at least 2
      years were similar to the overall group. On magnetic resonance arthrography, the
      shoulders with posterior instability were found to have significantly greater
      chondrolabral and osseous retroversion in comparison with controls (P < .001 and
      P = .008, respectively). CONCLUSION: Arthroscopic capsulolabral reconstruction is
      an effective, reliable treatment for symptomatic unidirectional recurrent
      posterior glenohumeral instability in an athletic population. Overall, 89% of
      patients were able to return to sport, with 67% of patients able to return to the
      same level postoperatively.

PMID- 16567459
TI  - Medial patellofemoral ligament reconstruction in patients with lateral patellar
      instability and trochlear dysplasia.
AB  - BACKGROUND: Reconstruction of the medial patellofemoral ligament has been proven
      to restore stability in patients with lateral patellar instability. No study to
      date has examined the results in a patient population with the predisposing
      factor of femoral trochlear dysplasia. HYPOTHESIS: Reconstruction of the medial
      patellofemoral ligament restores stability and provides pain relief in patients
      who have lateral patellar instability in association with trochlear dysplasia.
      STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-four patients
      with chronic patellar instability and trochlear dysplasia were treated with
      medial patellofemoral ligament reconstruction using an adductor tendon autograft,
      bone-quadriceps tendon autograft, or bone-patellar tendon allograft. All patients
      were evaluated preoperatively and postoperatively with Kujala, Lysholm, and
      Tegner scores at a minimum of 24 months. RESULTS: Thirty-four patients were
      followed for a mean of 66.5 months (range, 24-130 months) after surgery. Kujala
      scores improved from 53.3 to 90.7, Lysholm scores improved from 52.4 to 92.1, and
      Tegner activity scores improved from 3.1 to 5.1. All improvements were highly
      statistically significant (P < .001). No statistical difference was found between
      the postoperative Lysholm, Kujala, and Tegner scores and the degree of dysplasia,
      graft type, or degree of symptoms. There were 85.3% and 91.1% good and excellent
      results based on Kujala and Lysholm scores, respectively. No recurrent
      dislocations have occurred. CONCLUSION: Medial patellofemoral ligament
      reconstruction provides excellent long-term pain relief and functional return in
      patients with patellar instability and femoral trochlear dysplasia. In addition,
      reconstruction prevents recurrent dislocation, despite the diminished bony
      constraint of a dysplastic trochlea.

PMID- 16567460
TI  - Elongation and structural properties of meniscal repair using suture techniques
      in distraction and shear force scenarios: biomechanical evaluation using a cyclic
      loading protocol.
AB  - BACKGROUND: Most biomechanical studies on meniscal repairs have focused on
      testing distraction scenarios to evaluate structural properties of the repaired
      meniscus. An application of shear forces might replicate the in vivo situation
      more closely. HYPOTHESIS: In the shear force scenario, meniscal repair using a
      vertical suture technique will result in significantly less elongation when
      subjected to a cyclic loading protocol than that resulting from a horizontal
      suture technique. STUDY DESIGN: Controlled laboratory study. METHODS: In fresh
      frozen porcine menisci (n = 10 in each group), horizontal and vertical 2.0
      Ethibond suturing techniques were tested in distraction and shear force
      scenarios. Elongation after 1000 cycles between 5 and 20 N and the structural
      properties such as stiffness, yield load, maximum load to failure, and failure
      mode were evaluated using a testing machine at a rate of 12.5 mm/s. RESULTS: In
      the distraction force scenario, no statistically significant difference in
      elongation after cyclic loading was found between specimens repaired with
      vertical or horizontal suture techniques. After 1000 cycles of cyclic loading in
      the shear force scenario, the horizontal suturing revealed significantly less
      elongation (2.8 +/- 1.1 mm) than did the vertical suture technique (4.6 +/- 2.0
      mm). No statistically significant difference in yield and maximum load was found
      (P > .05). CONCLUSION: The results of the present study do not support the
      authors' hypothesis. In the shear force test, horizontal sutures were superior to
      vertical suture techniques. CLINICAL RELEVANCE: Meniscal repair with horizontal
      suture techniques can withstand elongation due to shear forces more effectively
      than can vertical mattress sutures.

PMID- 16567462
TI  - Infectious disease outbreaks in competitive sports: a review of the literature.
AB  - Recent outbreaks of infectious diseases in athletes in competitive sports have
      stimulated considerable interest. The environments in which these athletes
      compete, practice, receive therapy for injuries, and travel, both domestically
      and internationally, provide varied opportunities for the transmission of
      infectious organisms. The purpose of this medical literature review is to
      identify the agents most commonly reported in the medical literature as
      responsible for infectious disease outbreaks in specific sports and their modes
      of transmission and to guide targeted prevention efforts. A literature review of
      English-language articles in medical publications that reported outbreaks of
      infectious diseases in competitive athletes was conducted in PubMed MEDLINE from
      1966 through May 2005. Outbreaks that were solely food borne were excluded. Fifty
      nine reports of infectious disease outbreaks in competitive sports were
      identified in the published medical literature. Herpes simplex virus infections
      appear to be common among wrestlers and rugby players, with no single strain
      responsible for the outbreaks. Methicillin-resistant Staphylococcus aureus was
      responsible for several recent outbreaks of soft tissue and skin infections among
      collegiate and professional athletes. The most common mode of transmission in
      outbreaks was direct, person-to-person (primarily skin-to-skin) contact. Blood
      borne exposure was implicated in 2 confirmed outbreaks of hepatitis. Airborne and
      vector transmissions were rarely reported. This review provides an overview of
      infectious disease outbreaks thought to be either serious enough or unusual
      enough to report. Appropriate surveillance of the frequency of infections will
      allow sports medicine staff to identify outbreaks quickly and take necessary
      measures to contain further transmission and prevent future outbreaks.

PMID- 16567461
TI  - Comparing the incidence of anterior cruciate ligament injury in collegiate
      lacrosse, soccer, and basketball players: implications for anterior cruciate
      ligament mechanism and prevention.
AB  - BACKGROUND: Female college basketball and soccer athletes have higher rates of
      anterior cruciate ligament injury than do their male counterparts. Rates of
      anterior cruciate ligament injuries for women and men in collegiate lacrosse have
      not been examined. Understanding anterior cruciate ligament injury patterns in
      lacrosse, a full-contact sport for men and noncontact sport for women, could
      further injury prevention efforts. HYPOTHESES: Female anterior cruciate ligament
      injury rates will decrease over time owing to longer participation in sports.
      Lacrosse anterior cruciate ligament injury rates will be lower than rates in
      basketball and soccer possibly owing to beneficial biomechanics of carrying a
      lacrosse stick. STUDY DESIGN: Cohort study (Prevalence); Level of evidence, 2.
      METHODS: Data from the National Collegiate Athletic Association Injury
      Surveillance System were analyzed to compare men's and women's anterior cruciate
      ligament injuries in basketball, lacrosse, and soccer over 15 years. RESULTS:
      Anterior cruciate ligament injury rates in women's basketball and soccer were
      0.28 and 0.32 injuries per 1000 athlete exposures, respectively, and did not
      decline over the study period. In men's basketball, injury rate fluctuated
      between 0.03 and 0.13 athlete exposures. Rates of anterior cruciate ligament
      injury did not significantly change in men's soccer over the study period. The
      rate of anterior cruciate ligament injury in men's lacrosse (0.17 athlete
      exposures, P < .05) was significantly higher than in men's basketball (0.08
      athlete exposures) and soccer (0.12 athlete exposures). Injury rate in women's
      lacrosse (0.18 athlete exposures, P < .05) was significantly lower than in
      women's basketball and soccer. CONCLUSION: There was no discernable change in
      rate of anterior cruciate ligament injury in men or women during the study
      period. Men's lacrosse is a high-risk sport for anterior cruciate ligament
      injury. Unlike basketball and soccer, the rates of anterior cruciate ligament
      injury are essentially the same in men's and women's lacrosse. The level of
      allowed contact in pivoting sports may be a factor in determining sport-specific
      anterior cruciate ligament risk.

PMID- 16567463
TI  - Shedding light on cones.

PMID- 16567464
TI  - Physiological features of the S- and M-cone photoreceptors of wild-type mice from
      single-cell recordings.
AB  - Cone cells constitute only 3% of the photoreceptors of the wild-type (WT) mouse.
      While mouse rods have been thoroughly investigated with suction pipette
      recordings of their outer segment membrane currents, to date no recordings from
      WT cones have been published, likely because of the rarity of cones and the
      fragility of their outer segments. Recently, we characterized the photoreceptors
      of Nrl(-/-) mice, using suction pipette recordings from their "inner segments"
      (perinuclear region), and found them to be cones. Here we report the use of this
      same method to record for the first time the responses of single cones of WT
      mice, and of mice lacking the alpha-subunit of the G-protein transducin
      (G(t)alpha(-/-)), a loss that renders them functionally rodless. Most cones were
      found to functionally co-express both S- (lambda(max) = 360 nm) and M-
      (lambda(max) = 508 nm) cone opsins and to be maximally sensitive at 360 nm ("S
      cones"); nonetheless, all cones from the dorsal retina were found to be maximally
      sensitive at 508 nm ("M-cones"). The dim-flash response kinetics and absolute
      sensitivity of S- and M-cones were very similar and not dependent on which of the
      coexpressed cone opsins drove transduction; the time to peak of the dim-flash
      response was approximately 70 ms, and approximately 0.2% of the circulating
      current was suppressed per photoisomerization. Amplification in WT cones (A
      approximately 4 s(-2)) was found to be about twofold lower than in rods (A
      approximately 8 s(-2)). Mouse M-cones maintained their circulating current at
      very nearly the dark adapted level even when >90% of their M-opsin was bleached.
      S-cones were less tolerant to bleached S-opsin than M-cones to bleached M-opsin,
      but still far more tolerant than mouse rods to bleached rhodopsin, which exhibit
      persistent suppression of nearly 50% of their circulating current following a 20%
      bleach. Thus, the three types of mouse opsin appear distinctive in the degree to
      which their bleached, unregenerated opsins generate "dark light."

PMID- 16567465
TI  - Roles of K149, G352, and H401 in the channel functions of ClC-0: testing the
      predictions from theoretical calculations.
AB  - The ClC family of Cl(-) channels and transporters comprises membrane proteins
      ubiquitously present in species ranging from prokaryotes to mammals. The recently
      solved structures of the bacterial ClC proteins have provided a good model to
      guide the functional experiments for the eukaryotic Cl(-) channels. Theoretical
      calculations based on the bacterial ClC structures have identified several
      residues critical for the Cl(-) binding energy in the Cl(-) transport pathway. It
      was speculated that the corresponding residues in eukaryotic Cl(-) channels might
      play similar roles for the channel functions. In this study, we made a series of
      mutations in three such residues in eukaryotic ClC Cl(-) channels (K149, G352,
      and H401 in ClC-0) and studied the functional consequences on the channel
      properties. A cysteine modification approach was also employed to evaluate the
      electrostatic effects of the charge placed at these three positions. The
      experimental results revealed that among the three residues tested, K149 plays
      the most important role in controlling both the gating and the permeation
      functions of ClC-0. On the other hand, mutations of H401 alter the channel
      conductance but not the gating properties, while mutations of G352 result in very
      little functional consequence. The mutation of K149 into a neutral residue
      leucine (K149L) shifts the activation curve and leads to flickery channel
      openings. The anion permeability ratios derived from bi-ionic experiments are
      also significantly altered in that the selectivity of Cl(-) over other anions is
      decreased. Furthermore, removing the positive charge at this position reduces and
      increases, respectively, the accessibility of the negatively and positively
      charged methane thiosulfonate reagents to the pore. The control of the
      accessibility to charged MTS reagents and the regulation of the anion permeation
      support the idea that K149 exerts an electrostatic effect on the channel
      function, confirming the prediction from computational studies.

PMID- 16567466
TI  - Mechanism of beta4 subunit modulation of BK channels.
AB  - Large-conductance (BK-type) Ca(2+)-activated potassium channels are activated by
      membrane depolarization and cytoplasmic Ca(2+). BK channels are expressed in a
      broad variety of cells and have a corresponding diversity in properties.
      Underlying much of the functional diversity is a family of four tissue-specific
      accessory subunits (beta1-beta4). Biophysical characterization has shown that the
      beta4 subunit confers properties of the so-called "type II" BK channel isotypes
      seen in brain. These properties include slow gating kinetics and resistance to
      iberiotoxin and charybdotoxin blockade. In addition, the beta4 subunit reduces
      the apparent voltage sensitivity of channel activation and has complex effects on
      apparent Ca(2+) sensitivity. Specifically, channel activity at low Ca(2+) is
      inhibited, while at high Ca(2+), activity is enhanced. The goal of this study is
      to understand the mechanism underlying beta4 subunit action in the context of a
      dual allosteric model for BK channel gating. We observed that beta4's most
      profound effect is a decrease in P(o) (at least 11-fold) in the absence of
      calcium binding and voltage sensor activation. However, beta4 promotes channel
      opening by increasing voltage dependence of P(o)-V relations at negative membrane
      potentials. In the context of the dual allosteric model for BK channels, we find
      these properties are explained by distinct and opposing actions of beta4 on BK
      channels. beta4 reduces channel opening by decreasing the intrinsic gating
      equilibrium (L(0)), and decreasing the allosteric coupling between calcium
      binding and voltage sensor activation (E). However, beta4 has a compensatory
      effect on channel opening following depolarization by shifting open channel
      voltage sensor activation (Vh(o)) to more negative membrane potentials. The
      consequence is that beta4 causes a net positive shift of the G-V relationship
      (relative to alpha subunit alone) at low calcium. At higher calcium, the
      contribution by Vh(o) and an increase in allosteric coupling to Ca(2+) binding
      (C) promotes a negative G-V shift of alpha+beta4 channels as compared to alpha
      subunits alone. This manner of modulation predicts that type II BK channels are
      downregulated by beta4 at resting voltages through effects on L(0). However,
      beta4 confers a compensatory effect on voltage sensor activation that increases
      channel opening during depolarization.

PMID- 16567467
TI  - Ethical and legal issues in research involving human subjects: do you want a
      piece of me?
AB  - The conduct of biomedical research involving the participation of human beings
      implicates a variety of ethical concerns pertaining to such values as dignity,
      bodily integrity, autonomy, and privacy. These ethical concerns have been
      translated into a complex regulatory apparatus in the USA, containing specific
      legal provisions concerning such matters as participant safety, informed consent,
      and confidentiality. A topic of particular interest for pathologists is the
      handling of human tissue specimens that may be used for present, or stored for
      future, research purposes. This article examines the ethical and legal
      ramifications of obtaining and storing tissue samples for research purposes, with
      special attention to the issues of informed consent and confidentiality.

PMID- 16567468
TI  - Biochemical markers of acute pancreatitis.
AB  - Serum amylase remains the most commonly used biochemical marker for the diagnosis
      of acute pancreatitis, but its sensitivity can be reduced by late presentation,
      hypertriglyceridaemia, and chronic alcoholism. Urinary trypsinogen-2 is
      convenient, of comparable diagnostic accuracy, and provides greater (99%)
      negative predictive value. Early prediction of the severity of acute pancreatitis
      can be made by well validated scoring systems at 48 hours, but the novel serum
      markers procalcitonin and interleukin 6 allow earlier prediction (12 to 24 hours
      after admission). Serum alanine transaminase >150 IU/l and jaundice suggest a
      gallstone aetiology, requiring endoscopic retrograde cholangiopancreatography.
      For obscure aetiologies, serum calcium and triglycerides should be measured.
      Genetic polymorphisms may play an important role in "idiopathic" acute recurrent
      pancreatitis.

PMID- 16567469
TI  - Comparison of renal function markers in Kuwaiti patients with sickle cell
      disease.
AB  - BACKGROUND: Proteinuria is a common manifestation of renal disease which is a
      significant cause of morbidity in patients with sickle cell disease (SCD).
      OBJECTIVE: To evaluate and compare cystatin C, beta(2)-microglobulin, and
      creatinine as markers of renal disease in relation to the degree of proteinuria
      and other complications of SCD. METHODS: 24 h urine collections were used for
      estimation of urine protein and creatinine clearance in 59 patients with SCD.
      Results were correlated with plasma cystatin C, beta(2)-microglobulin,
      creatinine, glomerular filtration rate (GFR; derived from plasma creatinine by
      Cockcroft-Gault, MDRD formulae, and calculated cystatin C clearance), and
      clinical and haematological variables. RESULTS: Comparing the different methods
      of GFR, the proportion of patients with hyperfiltration (GFR >140 ml/min) were
      30.5% (MDRD), 44.1% (Cockcroft-Gault), and 10.2 % (calculated cystatin C
      clearance). Cystatin C was the most consistent marker of hyperfiltration. The
      endogenous markers of GFR showed an increasing trend with increasing proteinuria,
      but haematological variables were not correlated with cystatin C, beta(2)
      microglobulin, or plasma creatinine. Urine protein excretion was correlated with
      age (r = 0.33) and significant proteinuria was present in 13.6% of patients.
      Patients with proteinuria had lower haemoglobin concentration (p = 0.027) than
      those without proteinuria but HbF was not related to the degree of proteinuria or
      to markers of GFR. CONCLUSIONS: Markers of GFR show variable ability to identify
      hyperfiltration in patients with SCD, but cystatin C is the best endogenous
      marker. Proteinuria is associated with age, haemoglobin, and abnormalities of
      GFR. Routine screening is recommended to allow for early detection and
      intervention.

PMID- 16567470
TI  - Rapid fixation of brains: a viable alternative?
AB  - AIM: Recent events surrounding postmortem practices have necessitated several
      changes in the way necropsies are conducted both within the medicolegal and
      hospital settings. These changes have resulted in a striking reduction in the
      frequency of brain retention for neuropathological examination. Aberdeen Royal
      Infirmary, responding quickly to rising concerns among bereaved relatives
      regarding organ retention, instituted a change in practice regarding the
      examination of brains at necropsy as early as 2001. The new protocol involved
      subjecting the brain to rapid fixation using combined immersion and perfusion
      techniques. This allows return of the organ to the body without unreasonable
      delay to the funeral. In this article, we present the results of a retrospective
      audit comparing the efficacy of the new method against the conventional fixation
      protocol. METHODS: An equal number of postmortem brains were selected randomly
      from the year 1998 (following the usual fixation protocol), and from the year
      2001 (following the new method). A three tier scoring system was devised to
      assess section and staining quality, and a single observer scored all the cases.
      RESULTS: No statistical difference was noted in the quality of sections prepared
      by rapid fixation those by conventional fixation. Furthermore, the rapid method
      was more frequently adequate for diagnosis (considering scores of 2 and 3
      together) than the conventional method. CONCLUSION: Rapid fixation offers a
      viable alternative for detailed examination of brains at necropsy, without
      necessarily prolonging the retention of the organ.

PMID- 16567471
TI  - Increased expression of connexins 26 and 43 in lymph node metastases of breast
      cancer.
AB  - BACKGROUND: Gap junctions are intercellular channels composed of connexins, which
      mediate the direct passage of small molecules between neighbouring cells. They
      are involved in regulation of cell cycle, cell signalling, and differentiation,
      and probably invasion and metastasis. The role of connexins in the metastatic
      process is controversial, because some studies indicate that connexin expression
      is inversely correlated with metastatic capacity. In contrast, others demonstrate
      that connexins may be involved in metastasis. In addition, connexin status in
      breast cancer metastasis has not been widely studied. METHODS: We evaluated by
      immunohistochemistry the expression of connexin 26 (Cx26) and connexin 43 (Cx43)
      in primary breast tumours (PTs) and matched paired metastases to lymph nodes
      (MLNs). RESULTS: In PTs, we observed predominantly cytoplasmic localisation of
      evaluated connexins, indicating alterations in connexin expression in breast
      cancer cells. We demonstrated that expression of Cx26 and Cx43 was increased in
      MLNs compared with PTs (p<0.00001 and p<0.001, for CX26 and Cx43, respectively).
      In addition, Cx26 and Cx43 negative PTs developed Cx26 and Cx43 positive MLNs.
      Furthermore, besides increased cytoplasmic staining, enhanced membranous
      localisation of Cx43, typical of normal cells, was found in MLNs. Additionally,
      membranous Cx26 expression appeared only in metastatic breast cancer cells.
      CONCLUSIONS: These findings suggest that connexins may contribute to the
      efficient metastasising of breast cancer to the lymph nodes.

PMID- 16567472
TI  - Intrapatellar tendon lipoma with chondro-osseous differentiation: detection of
      HMGA2-LPP fusion gene transcript.
AB  - A 54 year old man developed an unusual lipoma in the patellar tendon, consisting
      of a fibro-adipose component and a chondro-osseous component. The fibro-adipose
      component contained mature adipocytes, lipoblasts, and fibroblasts; the chondro
      osseous component showed typical endochondral bone formation. Molecular analysis
      showed that the identical HMGA2-LPP fusion transcript-characteristic of lipoma,
      parosteal lipoma, and pulmonary chondroid hamartoma-was detectable in the both
      components.

PMID- 16567473
TI  - High grade prostatic intraepithelial neoplasia with squamous differentiation.
AB  - An unusual variant of prostatic intraepithelial neoplasia with prominent and
      extensive squamous differentiation is described. The lesion was identified in the
      transition zone of a 79 year old man with a three year history of increasing
      urinary obstructive symptoms and a clinical diagnosis of benign prostatic
      hyperplasia who underwent simple prostatectomy. Two years after surgery,
      prostatic biopsies showed atrophy and mild chronic inflammation, with no evidence
      of malignancy. This unusual intraepithelial lesion seems not to have been
      described before and may represent a new variant of high grade prostatic
      intraepithelial neoplasia (HGPIN) with squamous differentiation.

PMID- 16567474
TI  - Familial tumoral calcinosis and testicular microlithiasis associated with a new
      mutation of GALNT3 in a white family.
AB  - BACKGROUND: Familial tumoral calcinosis (FTC) is a rare autosomal recessive
      disease characterised by the development of multiple calcified masses in
      periarticular soft tissues; GALNT3 gene mutations have recently been described in
      an African American and in a Druse Arab family with FTC. OBJECTIVE: To report the
      clinical and histological features caused by a new GALNT3 mutation in a white
      family. RESULTS: Homozygosity for the nonsense mutation Lys463X was found in both
      affected siblings, who displayed a classic phenotype, the male also having
      testicular microlithiasis. He is the first subject described with testicular
      microlithiasis in FTC. CONCLUSIONS: The high testicular expression of GALNT3
      suggests that the gene alteration could act locally by causing deposition of
      calcium, and the testis may be an underestimated site of calcification in FTC.
      Autoimmune diseases are present in several members of the family. Although immune
      disorders have been described in FTC, autoimmunity does not segregate with the
      GALNT3 mutation in this family.

PMID- 16567475
TI  - Rapid diagnosis of Penicillium marneffei infection by fine needle aspiration
      cytology.
AB  - This report describes the use of fine needle aspiration (FNA) cytology to make a
      rapid diagnosis of Penicillium marneffei infection in an HIV positive patient. P
      marneffei is a thermally dimorphic fungus that is a mould at 25 degrees C and a
      yeast at 37 degrees C. It multiplies by fission. It can be easily mistaken for
      various other infections that are characterised by the presence of histiocytes
      with phagocytosed yeast cells. In smears the demonstration of yeast cells with a
      distinctive central septum confirms the diagnosis.

PMID- 16567476
TI  - Science to practice: Should biopsy be performed in potential liver donors when
      unenhanced CT shows an unacceptable degree of steatosis for transplantation?

PMID- 16567478
TI  - Leadership and organizational development: lessons from the USS Constitution and
      the age of fighting sail.

PMID- 16567479
TI  - Percutaneous image-guided urologic procedures.

PMID- 16567480
TI  - Neuroradiology in the humanities and social sciences.

PMID- 16567481
TI  - Imaging of fistula in ano.
AB  - Fistula in ano is a common condition that often recurs despite seemingly adequate
      surgery, usually because of infection that was missed at surgery. It is now
      increasingly recognized that preoperative imaging can help identify infection
      that would have otherwise gone unidentified. In particular, magnetic resonance
      (MR) imaging findings have been shown to influence surgery and markedly diminish
      the chance of recurrence; thus, preoperative imaging will become increasingly
      routine in the future. In this article, the authors describe the pathogenesis,
      classification, and imaging of fistula in ano, with an emphasis on MR imaging.
      Most important, the authors describe how the radiologist is well placed to answer
      the surgical riddles that must be solved for treatment to be effective.

PMID- 16567482
TI  - The solitary pulmonary nodule.
AB  - The imaging evaluation of a solitary pulmonary nodule is complex. Management
      decisions are based on clinical history, size and appearance of the nodule, and
      feasibility of obtaining a tissue diagnosis. The most reliable imaging features
      are those that are indicative of benignancy, such as a benign pattern of
      calcification and periodic follow-up with computed tomography for 2 years showing
      no growth. Fine-needle aspiration biopsy and core biopsy are important procedures
      that may obviate surgery if there is a specific benign diagnosis from the
      procedure. In using the various imaging and diagnostic modalities described in
      this review, one should strive to not only identify small malignant tumors--where
      resection results in high survival rates--but also spare patients with benign
      disease from undergoing unnecessary surgery.

PMID- 16567483
TI  - Breast microcalcifications: retrieval failure at prone stereotactic core and
      vacuum breast biopsy--frequency, causes, and outcome.
AB  - PURPOSE: To retrospectively determine the frequency and causes of failure to
      retrieve microcalcifications in nonpalpable lesions, as judged on a radiograph of
      the specimen, and to determine outcome in patients with those lesions. MATERIALS
      AND METHODS: Informed consent was obtained from each patient prior to biopsy. The
      institutional review board approved this HIPAA-compliant study and granted a
      waiver of informed consent. Retrospective review was performed of 1701
      consecutive nonpalpable microcalcification lesions in 1511 women aged 29-92 years
      (median age, 54 years) who underwent percutaneous stereotactic biopsy on a prone
      biopsy table. Biopsy was successively performed with 14-gauge core, 14-gauge
      vacuum, and 11-gauge vacuum devices, with mild selection bias, and for each
      lesion, biopsy was performed with one device. Radiographs of the specimen were
      obtained to see whether microcalcifications were retrieved. Patient,
      mammographic, and biopsy variables were correlated with negative radiographs of
      the specimen. At repeat biopsy or mammographic follow-up, outcome was evaluated
      in patients with benign histologic results and negative radiographs of the
      specimen by using Fisher exact test P values. RESULTS: Radiographs of the
      specimen were negative in 16% (30 of 182) of lesions at 14-gauge core biopsy, in
      4% (four of 96) of lesions at 14-gauge vacuum biopsy, and in 1% (19 of 1423) of
      lesions at 11-gauge vacuum biopsy (P < .001). Substantial bleeding was a
      significant factor (P < .001) in failure to retrieve microcalcifications at only
      11-gauge vacuum biopsy. Histologic results in 53 lesions with negative
      radiographs of the specimen were malignant (n = 6), indicated atypical
      hyperplasia (n = 6), or were benign (n = 41). Follow-up in patients with 40
      benign lesions was performed with repeat biopsy (n = 17, with malignancy in three
      lesions) or mammography (n = 23) for 15-128 months (median, 70 months); one
      patient with one lesion was lost to follow-up. CONCLUSION: Failure to retrieve
      microcalcifications was least common with 11-gauge directional vacuum-assisted
      biopsy and occurred in 1% (19 of 1423) of lesions. Cancer was missed in 8% (three
      of 40) of benign lesions in patients who were followed up.

PMID- 16567484
TI  - Effect of blood vessels on measurement of nodule volume in a chest phantom.
AB  - PURPOSE: To identify, by using a chest phantom, whether vessels that contact lung
      nodules measuring less than 5 mm in diameter will affect nodule volume
      assessment. MATERIALS AND METHODS: Forty synthetic nodules (20 with ground-glass
      attenuation and 20 with solid attenuation) that measured less than 5 mm in
      diameter were placed into a chest phantom either adjacent to (n = 30) or isolated
      from (n = 10) synthetic vessels. Nodules were imaged by using low-dose (20 mAs)
      and diagnostic (120 mAs) multi-detector row computed tomography (CT). Nodules
      that were known to lie in direct contact with vessels were confirmed by visual
      inspection. Nontargeted 1.25 x 1.00-mm sections were analyzed with a three
      dimensional computer-assisted method for measuring nodule volume. A mixed-model
      analysis of variance was used to examine the influence of several factors (eg,
      the presence of adjacent vessels; tube current-time product; and nodule
      attenuation, diameter, and location) on measurement error. RESULTS: The mean
      absolute error (MAE) for all nodules adjacent to vessels was 2.3 mm(3), which was
      higher than the MAE for isolated nodules (1.9 mm(3)) (P < .001). This difference
      proved significant only for diagnostic CT (2.2 mm(3) for nodules adjacent to
      vessels vs 1.3 mm(3) for nodules isolated from vessels) (P < .05). A larger MAE
      was noted for nodules with ground-glass attenuation (2.3 mm(3)) versus those with
      solid attenuation (2.0 mm(3)), for increasing nodule volume (1.66 mm(3) for
      nodules smaller than 20 mm(3) vs 2.83 mm(3) for nodules larger than 40 mm(3)),
      and for posterior nodule location (P < .05). CONCLUSION: The presence of a vessel
      led to a small yet significant increase in volume error on diagnostic-quality
      images. This represents less than one-third of the overall error, even for
      nodules larger than 40 mm(3) or approximately 4 mm in diameter. This increase,
      however, may be more important for smaller nodules with errors of less than 3
      mm(3).

PMID- 16567485
TI  - Tagging-based, electronically cleansed CT colonography: evaluation of patient
      comfort and image readability.
AB  - PURPOSE: To prospectively compare the homogeneity, adequacy, and patient
      acceptance of nonionic iodine-based regimens with those of a barium-based regimen
      for computed tomographic (CT) colonography with electronic subtraction cleansing.
      MATERIALS AND METHODS: After institutional review board approval and informed
      consent were obtained, 68 subjects (41 men (60%) men, 27 (40%) women; mean age,
      60 years +/- 6 [standard deviation]) with average or moderate risk factors for
      development of colorectal carcinoma were recruited and placed into three study
      groups. Group 1 (n = 25) ingested 150-mL aliquots of 2% barium sulfate suspension
      with meals and snacks for 48 hours prior to imaging, without other diet
      modification or a cathartic. Group 2 (n = 21) ingested 10-mL aliquots of nonionic
      iodinated contrast material (iopromide) with a concentration of 300 mg per
      milliliter with meals and snacks for 2 days before imaging, without diet
      modification or a cathartic. Group 3 (n = 22) ingested nonionic iodinated
      contrast material (iohexol) with a concentration of 300 mg per milliliter with
      meals and snacks for 2 days before imaging and ingested 34 g of magnesium citrate
      the evening prior to imaging. CT colonography was also performed on 10 control
      subjects who ingested polyethylene glycol electrolyte solution prior to imaging.
      Subjective and numerical measures of bowel preparation quality, homogeneity, and
      patient comfort among the noncathartic and cathartic cohorts were compared with
      nonparametric analysis of variance, the Fisher exact test, and the F test, as
      appropriate. The study was HIPAA compliant. RESULTS: Study subjects who received
      tagging preparations reported significantly improved discomfort scores when
      compared with those of the control subjects (P < .05, each comparison). There was
      no significant difference in discomfort scores among groups 1, 2, and 3. For each
      reader, scores of subtracted image readability were highest for group 3.
      Dichotomized rates of preparation "success" were also greatest for group 3.
      CONCLUSION: In this series, the patient discomfort scores were significantly
      improved with tagging preparations for CT colonography. Nonionic iodinated
      contrast material in conjunction with a hyperosmotic laxative (magnesium citrate)
      was associated with the best subjective and numerical indices of readability.

PMID- 16567487
TI  - Parkinson disease: pattern of functional MR imaging activation during deep brain
      stimulation of subthalamic nucleus--initial experience.
AB  - PURPOSE: To prospectively determine the pattern of functional magnetic resonance
      (MR) imaging activation at 3 T produced by deep brain stimulation (DBS) of
      subthalamic nucleus (STN) for treatment of Parkinson disease and to determine the
      safety of DBS electrode stimulation during functional MR imaging at 3 T.
      MATERIALS AND METHODS: Informed consent was obtained from all subjects
      participating in the study, and the study protocol was approved by the
      institutional review board at the Cleveland Clinic Foundation and was HIPAA
      compliant. After extensive phantom safety testing of DBS lead systems, five
      patients (three men, two women; mean age, 49.4 years +/- 14.5 [standard
      deviation]; range, 31-74 years) with percutaneously extended bilateral DBS
      electrodes placed in the STN for treatment of Parkinson disease were examined at
      3 T on the 1st or 2nd postoperative day. Imaging consisted of a three-dimensional
      anatomic data set with leads disconnected and a blood oxygen level-dependent
      functional MR image with a single lead connected to the external pulse generator
      in the MR imaging control room by using stimulation parameters previously
      determined to produce optimal stimulation for alleviation of symptoms. A total of
      nine leads were tested with the functional MR imaging protocol. Subjects
      underwent neurologic examination immediately before and after MR imaging.
      RESULTS: All five patients completed the study without change in their neurologic
      examination and with activation seen in eight of nine electrodes stimulated.
      Activation was seen in the ipsilateral basal ganglia in all subjects and
      ipsilateral thalamus in six of the electrodes tested. Two of the electrode
      stimulations demonstrated additional activation in the STN and/or substantia
      nigra region adjacent to the electrode tip. For three electrode stimulations,
      activation was seen in the contralateral superior cerebellum. CONCLUSION:
      Therapeutically effective DBS of STN can be performed safely during functional MR
      imaging at 3 T and produces a consistent pattern of ipsilateral activation of
      deep brain motor structures.

PMID- 16567486
TI  - Odontogenic orbital inflammation: clinical and CT findings--initial observations.
AB  - PURPOSE: To retrospectively review computed tomographic (CT) and clinical
      findings in patients with odontogenic orbital infection. MATERIALS AND METHODS:
      Approval from the institutional review board was obtained for chart and scan
      review, and informed consent was waived for this HIPAA-compliant study. Five
      patients, two male and three female (median age, 37 years; age range, 13-55
      years), who had odontogenic orbital cellulitis underwent clinical evaluation, CT
      scanning, and treatment. CT findings, including periapical lucency suggesting
      abscess, sinus opacification, and the route of spread of infection, were analyzed
      in each patient. Imaging, clinical, and surgical findings, including the initial
      clinical diagnosis and the presence of a periapical abscess at surgery and at
      pathologic examination, were compared. RESULTS: Periapical lucency and sinus
      opacification were seen in all patients. The route of infection spread was
      through either the premalar soft tissues or the maxillary sinuses. The
      odontogenic origin of the orbital infection was not clinically suspected in any
      patients. Correct diagnosis was later made at CT in all patients. Four patients
      had periapical abscesses at pathologic analysis, and the fifth patient had apical
      periodontitis at clinical analysis and granuloma at pathologic analysis. Dental
      surgery was required in each of the five patients for resolution of infection;
      four patients underwent extraction of the infected tooth, and one patient
      underwent incision and drainage of a periapical abscess. CONCLUSION: Abnormal
      periapical lucency, widening of the periodontal ligament space, and the presence
      of a subperiosteal abscess suggested an odontogenic origin of orbital infection.

PMID- 16567488
TI  - Outcome of percutaneous transhepatic venoplasty for hepatic venous outflow
      obstruction after living donor liver transplantation.
AB  - PURPOSE: To evaluate retrospectively the outcome of percutaneous transhepatic
      venoplasty of hepatic venous outflow obstruction after living donor liver
      transplantation (LDLT). MATERIALS AND METHODS: The institutional Human Subjects
      Research Review Board approved the interventional protocol and the retrospective
      study, for which informed consent was not required. Before treatment, informed
      consent was obtained from the patient or the patient's parents in all cases. Of
      26 consecutive patients (nine male, 17 female; median age, 9 years) suspected of
      having hepatic venous outflow obstruction after LDLT, 20 patients confirmed to
      have anastomotic outflow stenosis at percutaneous hepatic venography and
      manometry underwent venoplasty. Pressure gradients before and after venoplasty
      were evaluated by using a paired t test. Patients in whom obstruction recurred
      during follow-up were re-treated with venoplasty with or without expandable
      metallic stents. Patency was analyzed by using Kaplan-Meier analysis. RESULTS:
      The initial balloon venoplasty was technically successful in all 20 patients, all
      of whom had improved clinical findings. The pressure gradient +/- standard
      deviation was reduced from 14.6 mg Hg +/- 8.6 to 2.2 mg Hg +/- 2.4 (P < .001).
      Eleven patients had recurrent obstruction and were treated with balloon
      venoplasty; one of them underwent stent placement, as well as venoplasty. The
      primary (event-free) patency and 95% confidence interval (CI) at 3, 12, and 60
      months after venoplasty were 0.80 (95% CI: 0.62, 0.98), 0.60 (95% CI: 0.38,
      0.81), and 0.60 (95% CI: 0.38, 0.81), respectively. The primary assisted patency,
      maintained with repeated venoplasty and expandable metallic stents, was 1.00 at
      60 months. CONCLUSION: Percutaneous venoplasty is an effective treatment for
      hepatic venous outflow obstruction after LDLT.

PMID- 16567490
TI  - Case 93: thoracic splenosis.

PMID- 16567491
TI  - The golf ball-on-tee sign.

PMID- 16567492
TI  - Comments regarding the spur sign.

PMID- 16567493
TI  - A Fisher exact test will be more proper.

PMID- 16567494
TI  - "You can see a lot just by observing," but ...

PMID- 16567497
TI  - Controversy fuels trafficking of GPI-anchored proteins.
AB  - The model that glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs)
      take a direct transport route to the apical membrane of epithelial cells has
      recently been challenged. In this issue, Paladino et al. (p. 1023) and Hua et al.
      (p. 1035) show that the original view nevertheless holds. This closes a chapter
      in the winding story of GPI-AP trafficking but opens another phase, as the
      controversy has stimulated the development of new methodology.

PMID- 16567498
TI  - The epithelial-mesenchymal transition: new insights in signaling, development,
      and disease.
AB  - The conversion of an epithelial cell to a mesenchymal cell is critical to
      metazoan embryogenesis and a defining structural feature of organ development.
      Current interest in this process, which is described as an epithelial-mesenchymal
      transition (EMT), stems from its developmental importance and its involvement in
      several adult pathologies. Interest and research in EMT are currently at a high
      level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada
      (October 1-3, 2005). The meeting, which was hosted by The EMT International
      Association, was the second international EMT meeting, the first being held in
      Port Douglas, Queensland, Australia in October 2003. The EMT International
      Association was formed in 2002 to provide an international body for those
      interested in EMT and the reverse process, mesenchymal-epithelial transition,
      and, most importantly, to bring together those working on EMT in development,
      cancer, fibrosis, and pathology. These themes continued during the recent meeting
      in Vancouver. Discussion at the Vancouver meeting spanned several areas of
      research, including signaling pathway activation of EMT and the transcription
      factors and gene targets involved. Also covered in detail was the basic cell
      biology of EMT and its role in cancer and fibrosis, as well as the identification
      of new markers to facilitate the observation of EMT in vivo. This is particularly
      important because the potential contribution of EMT during neoplasia is the
      subject of vigorous scientific debate (Tarin, D., E.W. Thompson, and D.F.
      Newgreen. 2005. Cancer Res. 65:5996-6000; Thompson, E.W., D.F. Newgreen, and D.
      Tarin. 2005. Cancer Res. 65:5991-5995).

PMID- 16567499
TI  - A role for the RabA4b effector protein PI-4Kbeta1 in polarized expansion of root
      hair cells in Arabidopsis thaliana.
AB  - The RabA4b GTPase labels a novel, trans-Golgi network compartment displaying a
      developmentally regulated polar distribution in growing Arabidopsis thaliana root
      hair cells. GTP bound RabA4b selectively recruits the plant phosphatidylinositol
      4-OH kinase, PI-4Kbeta1, but not members of other PI-4K families. PI-4Kbeta1
      colocalizes with RabA4b on tip-localized membranes in growing root hairs, and
      mutant plants in which both the PI-4Kbeta1 and -4Kbeta2 genes are disrupted
      display aberrant root hair morphologies. PI-4Kbeta1 interacts with RabA4b through
      a novel homology domain, specific to eukaryotic type IIIbeta PI-4Ks, and PI
      4Kbeta1 also interacts with a Ca2+ sensor, AtCBL1, through its NH2 terminus. We
      propose that RabA4b recruitment of PI-4Kbeta1 results in Ca2+-dependent
      generation of PI-4P on this compartment, providing a link between Ca2+ and PI
      4,5P2-dependent signals during the polarized secretion of cell wall components in
      tip-growing root hair cells.

PMID- 16567500
TI  - Stu2p binds tubulin and undergoes an open-to-closed conformational change.
AB  - Stu2p from budding yeast belongs to the conserved Dis1/XMAP215 family of
      microtubule-associated proteins (MAPs). The common feature of proteins in this
      family is the presence of HEAT repeat-containing TOG domains near the NH2
      terminus. We have investigated the functions of the two TOG domains of Stu2p in
      vivo and in vitro. Our data suggest that Stu2p regulates microtubule dynamics
      through two separate activities. First, Stu2p binds to a single free tubulin
      heterodimer through its first TOG domain. A large conformational transition in
      homodimeric Stu2p from an open structure to a closed one accompanies the capture
      of a single free tubulin heterodimer. Second, Stu2p has the capacity to associate
      directly with microtubule ends, at least in part, through its second TOG domain.
      These two properties lead to the stabilization of microtubules in vivo, perhaps
      by the loading of tubulin dimers at microtubule ends. We suggest that this
      mechanism of microtubule regulation is a conserved feature of the Dis1/XMAP215
      family of MAPs.

PMID- 16567501
TI  - Vectorial insertion of apical and basolateral membrane proteins in polarized
      epithelial cells revealed by quantitative 3D live cell imaging.
AB  - Although epithelial cells are known to exhibit a polarized distribution of
      membrane components, the pathways responsible for delivering membrane proteins to
      their appropriate domains remain unclear. Using an optimized approach to three
      dimensional live cell imaging, we have visualized the transport of newly
      synthesized apical and basolateral membrane proteins in fully polarized filter
      grown Madin-Darby canine kidney cells. We performed a detailed quantitative
      kinetic analysis of trans-Golgi network (TGN) exit, passage through transport
      intermediates, and arrival at the plasma membrane using cyan/yellow fluorescent
      protein-tagged glycosylphosphatidylinositol-anchored protein and vesicular
      stomatitis virus glycoprotein as apical and basolateral reporters, respectively.
      For both pathways, exit from the TGN was rate limiting. Furthermore, apical and
      basolateral proteins were targeted directly to their respective membranes,
      resolving current confusion as to whether sorting occurs on the secretory pathway
      or only after endocytosis. However, a transcytotic protein did reach the apical
      surface after a prior appearance basolaterally. Finally, newly synthesized
      proteins appeared to be delivered to the entire lateral or apical surface,
      suggesting-contrary to expectations-that there is not a restricted site for
      vesicle docking or fusion adjacent to the junctional complex.

PMID- 16567502
TI  - CHMP5 is essential for late endosome function and down-regulation of receptor
      signaling during mouse embryogenesis.
AB  - Charged MVB protein 5 (CHMP5) is a coiled coil protein homologous to the yeast
      Vps60/Mos10 gene and other ESCRT-III complex members, although its precise
      function in either yeast or mammalian cells is unknown. We deleted the CHMP5 gene
      in mice, resulting in a phenotype of early embryonic lethality, reflecting
      defective late endosome function and dysregulation of signal transduction. Chmp5
      /- cells exhibit enlarged late endosomal compartments that contain abundant
      internal vesicles expressing proteins that are characteristic of late endosomes
      and lysosomes. This is in contrast to ESCRT-III mutants in yeast, which are
      defective in multivesicular body (MVB) formation. The degradative capacity of
      Chmp5-/- cells was reduced, and undigested proteins from multiple pathways
      accumulated in enlarged MVBs that failed to traffic their cargo to lysosomes.
      Therefore, CHMP5 regulates late endosome function downstream of MVB formation,
      and the loss of CHMP5 enhances signal transduction by inhibiting lysosomal
      degradation of activated receptors.

PMID- 16567503
TI  - CpG-induced tyrosine phosphorylation occurs via a TLR9-independent mechanism and
      is required for cytokine secretion.
AB  - Toll-like receptors (TLRs) recognize molecular patterns preferentially expressed
      by pathogens. In endosomes, TLR9 is activated by unmethylated bacterial DNA,
      resulting in proinflammatory cytokine secretion via the adaptor protein MyD88. We
      demonstrate that CpG oligonucleotides activate a TLR9-independent pathway
      initiated by two Src family kinases, Hck and Lyn, which trigger a tyrosine
      phosphorylation-mediated signaling cascade. This cascade induces actin
      cytoskeleton reorganization, resulting in cell spreading, adhesion, and motility.
      CpG-induced actin polymerization originates at the plasma membrane, rather than
      in endosomes. Chloroquine, an inhibitor of CpG-triggered cytokine secretion,
      blocked TLR9/MyD88-dependent cytokine secretion as expected but failed to inhibit
      CpG-induced Src family kinase activation and its dependent cellular responses.
      Knock down of Src family kinase expression or the use of specific kinase
      inhibitors blocked MyD88-dependent signaling and cytokine secretion, providing
      evidence that tyrosine phosphorylation is both CpG induced and an upstream
      requirement for the engagement of TLR9. The Src family pathway intersects the
      TLR9-MyD88 pathway by promoting the tyrosine phosphorylation of TLR9 and the
      recruitment of Syk to this receptor.

PMID- 16567504
TI  - Two distinct cytoplasmic regions of the beta2 integrin chain regulate RhoA
      function during phagocytosis.
AB  - AlphaMbeta2 integrins mediate phagocytosis of opsonized particles in a process
      controlled by RhoA, Rho kinase, myosin II, Arp2/3, and actin polymerization.
      AlphaMbeta2, Rho, Arp2/3, and F-actin accumulate underneath bound particles;
      however, the mechanism regulating Rho function during alphaMbeta2-mediated
      phagocytosis is poorly understood. We report that the binding of C3bi-opsonized
      sheep red blood cells (RBCs) to alphaMbeta2 increases Rho-GTP, but not Rac-GTP,
      levels. Deletion of the cytoplasmic domain of beta2, but not of alphaM, abolished
      Rho recruitment and activation, as well as phagocytic uptake. Interestingly, a 16
      amino acid (aa) region in the membrane-proximal half of the beta2 cytoplasmic
      domain was necessary for activating Rho. Three COOH-terminal residues (aa 758
      760) were essential for beta2-induced accumulation of Rho at complement receptor
      3 (CR3) phagosomes. Activation of Rho was necessary, but not sufficient, for its
      stable recruitment underneath bound particles or for uptake. However, recruitment
      of active Rho was sufficient for phagocytosis. Our data shed light on the
      mechanism of outside-in signaling, from ligated integrins to the activation of
      Rho GTPase signaling.

PMID- 16567505
TI  - 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit
      hepatic glucose phosphorylation by an AMP-activated protein kinase-independent
      effect on glucokinase translocation.
AB  - AMP-activated protein kinase (AMPK) controls glucose uptake and glycolysis in
      muscle. Little is known about its role in liver glucose uptake, which is
      controlled by glucokinase. We report here that 5-aminoimidazole-4-carboxamide-1
      beta-D-ribofuranoside (AICAR), metformin, and oligomycin activated AMPK and
      inhibited glucose phosphorylation and glycolysis in rat hepatocytes. In vitro
      experiments demonstrated that this inhibition was not due to direct
      phosphorylation of glucokinase or its regulatory protein by AMPK. By contrast,
      AMPK phosphorylated liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
      without affecting activity. Inhibitors of the endothelial nitric oxide synthase,
      stress kinases, and phosphatidylinositol 3-kinase pathways did not counteract the
      effects of AICAR, metformin, or oligomycin, suggesting that these signaling
      pathways were not involved. Interestingly, the inhibitory effect on glucose
      phosphorylation of these well-known AMPK activators persisted in primary cultured
      hepatocytes from newly engineered mice lacking both liver alpha1 and alpha2 AMPK
      catalytic subunits, demonstrating that this effect was clearly not mediated by
      AMPK. Finally, AICAR, metformin, and oligomycin were found to inhibit the glucose
      induced translocation of glucokinase from the nucleus to the cytosol by a
      mechanism that could be related to the decrease in intracellular ATP
      concentrations observed in these conditions.

PMID- 16567506
TI  - Widespread and stable pancreatic gene transfer by adeno-associated virus vectors
      via different routes.
AB  - Diabetes is a disease of epidemic proportions and is on the rise worldwide. Gene
      therapy has been actively pursued but limited by technical hurdles and profound
      inefficiency of direct gene transfer to the pancreas in vivo. Here, we show that,
      for the first time, appropriate serotypes of adeno-associated virus (AAV),
      coupled with a double-stranded vector DNA cassette, enable extensive and long
      term in vivo gene transfer in the adult mouse pancreas by three different
      delivery methods. Intraperitoneal and intravenous delivery of AAV8 effectively
      transduced exocrine acinar cells as well as endocrine beta-cells, while local
      pancreatic intraductal delivery of AAV6 showed the best efficiency in the beta
      cells among all AAV serotypes tested in this study. Nearly the entire islet
      population showed gene transfer but with distinct gene transfer efficiency and
      patterns when different delivery methods and vectors were used. Importantly,
      localized gene delivery coupled with an insulin promoter allowed extensive yet
      specific gene expression in the beta-cells. These effective new methods should
      provide useful tools to study diabetes pathogenesis and gene therapy.

PMID- 16567507
TI  - Accelerated diabetic nephropathy in mice lacking the peroxisome proliferator
      activated receptor alpha.
AB  - Peroxisome proliferator-activated receptor (PPAR)alpha, a member of the ligand
      activated nuclear receptor superfamily, plays an important role in lipid
      metabolism and glucose homeostasis and is highly expressed in the kidney. The
      present studies were aimed at determining the role of PPARalpha in the
      pathogenesis of diabetic nephropathy using PPARalpha-knockout mice and cultured
      murine mesangial cells. Diabetes was induced using a low-dose streptozotocin
      protocol in 8-week-old male 129 SvJ PPARalpha-knockout and wild-type mice.
      Diabetic PPARalpha-knockout and wild-type mice developed elevated fasting blood
      glucose (P < 0.001) and HbA1c levels (P < 0.001). Renal functional and
      histopathological changes in diabetic and nondiabetic PPARalpha-knockout and wild
      type mice were evaluated after 16 weeks of hyperglycemia. PPARalpha
      immunostaining of the cortical tubules of diabetic wild-type mice was elevated by
      hyperglycemia. In diabetic PPARalpha-knockout mice, renal disease with
      accompanying albuminuria, glomerular sclerosis, and mesangial area expansion was
      more severe than in diabetic wild-type mice (P < 0.05) and was accompanied by
      increased levels of serum free fatty acids and triglycerides (P < 0.01).
      Furthermore, they exhibited increased renal immunostaining for type IV collagen
      and osteopontin, which was associated with increased macrophage infiltration and
      glomerular apoptosis. There were no significant differences in these indexes of
      renal disease between nondiabetic PPARalpha-knockout and wild-type mice and
      diabetic PPARalpha wild-type mice. In vitro studies demonstrated that high
      glucose levels markedly increased the expression of type IV collagen,
      transforming growth factor-beta1, and the number of leukocytes adherent to
      cultured mesangial cells. Adherence of leukocytes was inhibited by the PPARalpha
      agonist fenofibrate. Taken together, PPARalpha deficiency appears to aggravate
      the severity of diabetic nephropathy through an increase in extracellular matrix
      formation, inflammation, and circulating free fatty acid and triglyceride
      concentrations. PPARalpha agonists may serve as useful therapeutic agents for
      type 1 diabetic nephropathy.

PMID- 16567508
TI  - ZO-1 expression and phosphorylation in diabetic nephropathy.
AB  - Cellular mechanisms responsible for the loss of capillary wall permselectivity in
      diabetic nephropathy are not well characterized. ZO-1 is a junctional protein
      involved in the assembly and proper function of a number of tight junctions and
      is also expressed at the junction of podocytes with the slit diaphragm. We
      investigated the effect of diabetes and high glucose concentration on the
      expression of ZO-1 in animal models of both type 1 and 2 diabetes and in rat
      glomerular epithelial cells. In diabetic animals, immunohistochemistry and
      Western blotting showed decreased expression of ZO-1 in glomeruli. Immunogold
      electron microscopy revealed redistribution of ZO-1 from the podocyte membrane to
      the cytoplasm in the diabetic animals. Exposure of rat glomerular epithelial
      cells to high glucose resulted in a decrease in the intensity of ZO-1 staining
      and redistribution of ZO-1 from the membrane to the cytoplasm, changes that are
      attenuated by blockade of the angiotensin II type 1 receptor. ZO-1 protein
      expression and serine and tyrosine phosphorylation of ZO-1 were also decreased in
      cells exposed to high glucose. These findings suggest that alterations in the
      content and localization of ZO-1 may be relevant to the pathogenesis of
      proteinuria in diabetes.

PMID- 16567510
TI  - Genetic mapping of disposition index and acute insulin response loci on
      chromosome 11q. The Insulin Resistance Atherosclerosis Study (IRAS) Family Study.
AB  - Glucose homeostasis, a defining characteristic of physiological glucose
      metabolism, is the result of complex feedback relationships with both genetic and
      environmental determinants that influence insulin sensitivity and beta-cell
      function. Relatively little is known about the genetic basis of glucose
      homeostasis phenotypes or their relationship to risk of diabetes. Our group
      previously published a genome scan for glucose homeostasis traits in 284 African
      American subjects from 21 pedigrees in the Insulin Resistance Atherosclerosis
      Study Family Study (IRASFS) and presented evidence for linkage to disposition
      index (DI) on chromosome 11q with a logarithm of odds (LOD) of 3.21 at 81 cM
      flanked by markers D11S2371 and D11S2002 (support interval from 71 to 96 cM). In
      this study, genotyping and analysis of an additional 214 African-American
      subjects in 21 pedigrees from the IRASFS yielded independent evidence of linkage
      to DI. When these two datasets were combined, a DI linkage peak was observed with
      an LOD of 3.89 at 78 cM (support interval from 67 to 89 cM). Fine mapping with 15
      additional microsatellite markers in this 11q region for the entire 42 pedigrees
      resulted in an LOD score of 4.80 at 80 cM near marker D11S937 (support interval
      from 76 to 84 cM). In these 42 pedigrees, there was also suggestive evidence for
      linkage to acute insulin response (AIR) at two separate locations flanking the DI
      peak (64 cM, LOD 2.77, flanked by markers D11S4076 and D11S981; and 85 cM, LOD
      2.54, flanked by markers D11S4172 and D11S2002). No evidence of linkage to the
      insulin sensitivity index (S(i)) was observed. Nine positional candidate genes
      were evaluated for association to DI and AIR. Among these candidates, single
      nucleotide polymorphisms (SNPs) in muscle glycogen phosphorylase showed evidence
      of association with DI (P < 0.011). In addition, SNPs in the pyruvate carboxylase
      gene showed evidence of association (P < 0.002) with AIR. Further analysis of
      these candidate genes, however, did not provide evidence that these SNPs
      accounted for the evidence of linkage to either DI or AIR. These detailed genetic
      analyses provide strong evidence of a DI locus on 11q in African-American
      pedigrees, with additional suggestive evidence of independent AIR loci in the
      same region.

PMID- 16567509
TI  - Contribution of aldose reductase to diabetic hyperproliferation of vascular
      smooth muscle cells.
AB  - The objective of this study was to determine whether the polyol pathway enzyme
      aldose reductase mediates diabetes abnormalities in vascular smooth muscle cell
      (SMC) growth. Aldose reductase inhibitors (tolrestat or sorbinil) or antisense
      aldose reductase mRNA prevented hyperproliferation of cultured rat aortic SMCs
      induced by high glucose. Cell cycle progression in the presence of high glucose
      was blocked by tolrestat, which induced a G0-G1 phase growth arrest. In situ,
      diabetes increased SMC growth and intimal hyperplasia in balloon-injured carotid
      arteries of streptozotocin-treated rats, when examined 7 or 14 days after injury.
      Treatment with tolrestat (15 mg x kg(-1) x day(-1)) diminished intimal
      hyperplasia and decreased SMC content of the lesion by 25%. Although tolrestat
      treatment increased immunoreactivity of the lesion with antibodies raised against
      protein adducts of the lipid peroxidation product 4-hydroxy trans-2-nonenal, no
      compensatory increase in lesion fibrosis was observed. Collectively, these
      results suggest that inhibition of aldose reductase prevents glucose-induced
      stimulation of SMC growth in culture and in situ. Even though inhibition of
      aldose reductase increases vascular oxidative stress, this approach may be useful
      in preventing abnormal SMC growth in vessels of diabetic patients.

PMID- 16567511
TI  - A polymorphism in the AMPKalpha2 subunit gene is associated with insulin
      resistance and type 2 diabetes in the Japanese population.
AB  - AMP-activated protein kinase (AMPK) acts as a fuel gauge for glucose and lipid
      metabolism. The gene encoding the alpha2 isoform of the catalytic subunit of AMPK
      (PRKAA2) is located at one of the Japanese type 2 diabetes loci mapped by our
      previous genome scan (1p36-32). PRKAA2 is, therefore, a good candidate gene for
      insulin resistance and type 2 diabetes. We screened all nine exons, their exon
      intron boundaries, and the 5' and 3' flanking regions of PRKAA2 to identify
      single nucleotide polymorphisms (SNPs), and we genotyped 192 type 2 diabetic
      patients and 272 nondiabetic subjects to assess possible associations between
      genotypes or haplotypes and type 2 diabetes. None of the 10 SNPs genotyped was
      associated with type 2 diabetes, but the haplotype analysis, consisting of six
      representative SNPs, revealed one haplotype, with the A (minor) allele for
      rs2051040 and a major allele for the other five SNPs, to be associated with type
      2 diabetes (P = 0.009). This finding was confirmed in two larger replication
      samples (657 case and 360 control subjects, P = 0.021; and 356 case and 192
      control subjects from the same area in Japan, P = 0.007) and a significant P
      value was obtained in the joint haplotype analysis of all samples (1,205 case and
      824 control subjects, P = 0.0001). Furthermore, insulin resistance was associated
      with rs2051040 in nondiabetic subjects, and those with the A (minor) allele had a
      higher homeostasis model assessment of insulin resistance index than those who
      did not (initial control subjects [n = 272], P = 0.002; and joint replication
      control subjects [n = 552], P = 0.037). We speculate that the PRKAA2 gene
      influences insulin resistance and susceptibility to type 2 diabetes in the
      Japanese population.

PMID- 16567512
TI  - Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated
      receptor-gamma-dependent mechanism in mice.
AB  - Adiponectin has insulin-sensitizing, antiatherogenic, and anti-inflammatory
      properties, but little is known about factors that regulate its secretion. To
      examine the effect of fish oil on adiponectin secretion, mice were fed either a
      control diet or isocaloric diets containing 27% safflower oil or 27, 13.5, and 8%
      menhaden fish oil. Within 15 days, fish oil feeding raised plasma adiponectin
      concentrations two- to threefold in a dose-dependent manner, and the
      concentrations remained approximately twofold higher for 7 days when the fish oil
      diet was replaced by the safflower oil diet. Within 24 h, fish oil markedly
      induced transcription of the adiponectin gene in epididymal adipose tissue but
      not in subcutaneous fat. The increase of plasma adiponectin by fish oil was
      completely blocked by administration of the peroxisome proliferator-activated
      receptor (PPAR)gamma inhibitor bisphenol-A-diglycidyl ether. In contrast, there
      was no effect of fish oil feeding on adiponectin secretion in PPARalpha-null
      mice. These data suggest that fish oil is a naturally occurring potent regulator
      of adiponectin secretion in vivo and that it does so through a PPARgamma
      dependent and PPARalpha-independent manner in epididymal fat.

PMID- 16567513
TI  - Increased brain monocarboxylic acid transport and utilization in type 1 diabetes.
AB  - We hypothesized that increased capacity for brain utilization of nonglucose
      substrates (monocarboxylic acids [MCAs]) by upregulation of the MCA transporters
      may contribute metabolic substrates during hypoglycemia. To test this hypothesis,
      we assessed brain acetate metabolism in five well-controlled type 1 diabetic
      subjects and six nondiabetic control subjects using 13C magnetic resonance
      spectroscopy during infusions of [2-(13)C]acetate during hypoglycemia
      (approximately 55 mg/dl). Acetate is transported into the brain through MCA
      transporters that are also used for lactate and ketones. Brain acetate
      concentrations were over twofold higher in the subjects with diabetes than the
      control subjects (P = 0.01). The fraction of oxidative metabolism from acetate (P
      = 0.015) and the rate of MCA transport (P = 0.01) were also approximately twofold
      higher in the diabetic subjects. We conclude that during hypoglycemia MCA
      transport in the brain was increased by approximately twofold in patients with
      well-controlled type 1 diabetes, as reflected by higher brain acetate
      concentrations and rates of acetate oxidation. This upregulation would
      potentially allow a similar twofold increase in the transport of other MCAs,
      including lactate, during insulin-induced hypoglycemia. These data are consistent
      with the hypothesis that upregulation of MCA transport may contribute to the
      maintenance of brain energetics during hypoglycemia in patients with type 1
      diabetes.

PMID- 16567514
TI  - Group 1B phospholipase A2-mediated lysophospholipid absorption directly
      contributes to postprandial hyperglycemia.
AB  - Postprandial hyperglycemia is an early indicator of abnormality in glucose
      metabolism leading to type 2 diabetes. However, mechanisms that contribute to
      postprandial hyperglycemia have not been identified. This study showed that mice
      with targeted inactivation of the group 1B phospholipase A2 (Pla2g1b) gene
      displayed lower postprandial glycemia than that observed in wild-type mice after
      being fed a glucose-rich meal. The difference was caused by enhanced postprandial
      glucose uptake by the liver, heart, and muscle tissues as well as altered
      postprandial hepatic glucose metabolism in the Pla2g1b-/- mice. These differences
      were attributed to a fivefold decrease in the amount of dietary phospholipids
      absorbed as lysophospholipids in Pla2g1b-/- mice compared with that observed in
      Pla2g1b+/+ mice. Elevating plasma lysophospholipid levels in Pla2g1b-/- mice via
      intraperitoneal injection resulted in glucose intolerance similar to that
      exhibited by Pla2g1b+/+ mice. Studies with cultured hepatoma cells revealed that
      lysophospholipids dose-dependently suppressed insulin-stimulated glycogen
      synthesis. These results demonstrated that reduction of lysophospholipid
      absorption enhances insulin-mediated glucose metabolism and is protective against
      postprandial hyperglycemia.

PMID- 16567515
TI  - Opposite effect of JAK2 on insulin-dependent activation of mitogen-activated
      protein kinases and Akt in muscle cells: possible target to ameliorate insulin
      resistance.
AB  - Many cytokines increase their receptor affinity for Janus kinases (JAKs).
      Activated JAK binds to signal transducers and activators of transcription,
      insulin receptor substrates (IRSs), and Shc. Intriguingly, insulin acting through
      its own receptor kinase also activates JAK2. However, the impact of such
      activation on insulin action remains unknown. To determine the contribution of
      JAK2 to insulin signaling, we transfected L6 myotubes with siRNA against JAK2
      (siJAK2), reducing JAK2 protein expression by 75%. Insulin-dependent
      phosphorylation of IRS1/2 and Shc was not affected by siJAK2, but insulin-induced
      phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular
      signal-related kinase, p38, and Jun NH2-terminal kinase and their respective
      upstream kinases MKK1/2, MKK3/6, and MKK4/7 was significantly lowered when JAK2
      was depleted, correlating with a significant drop in insulin-mediated cell
      proliferation. These effects were reproduced by the JAK2 inhibitor AG490.
      Conversely, insulin-stimulated Akt phosphorylation, glucose uptake, and GLUT4
      translocation were not affected by siJAK2. Interestingly, in two insulin
      resistant states, siJAK2 led to partial restoration of Akt phosphorylation and
      glucose uptake stimulation but not of the MAPK pathway. These results suggest
      that JAK2 may depress the Akt to glucose uptake signaling axis selectively in
      insulin-resistant states. Inhibition of JAK2 may be a useful strategy to relieve
      insulin resistance of metabolic outcomes.

PMID- 16567516
TI  - Insulin signaling in human visceral and subcutaneous adipose tissue in vivo.
AB  - In this study, we evaluated the activation of various insulin signaling molecules
      in human fat in vivo and compared signaling reactions in visceral and
      subcutaneous fat depots. Paired abdominal omental and subcutaneous fat biopsies
      were obtained from nonobese subjects with normal insulin sensitivity under basal
      conditions and 6 and 30 min following administration of intravenous insulin.
      Insulin receptor phosphorylation was more intense and rapid and insulin receptor
      protein content was greater in omental than in subcutaneous adipose tissue (P <
      0.05). Insulin-induced phosphorylation of Akt also occurred to a greater extent
      and earlier in omental than in subcutaneous fat (P < 0.05) in the absence of
      significant changes in Akt protein content. Accordingly, phosphorylation of the
      Akt substrate glycogen synthase kinase-3 was more responsive to insulin
      stimulation in omental fat. Protein content of extracellular signal-regulated
      kinase (ERK)-1/2 was threefold higher in omental than in subcutaneous fat (P <
      0.05), and ERK phosphorylation showed an early 6-min peak in omental fat, in
      contrast with a more gradual increase observed in subcutaneous fat. In
      conclusion, the adipocyte insulin signaling system of omental fat shows greater
      and earlier responses to insulin than that of subcutaneous fat. These findings
      may contribute to explain the biological diversity of the two fat depots.

PMID- 16567517
TI  - Characterization of peripheral circadian clocks in adipose tissues.
AB  - First described in the suprachiasmatic nucleus, circadian clocks have since been
      found in several peripheral tissues. Although obesity has been associated with
      dysregulated circadian expression profiles of leptin, adiponectin, and other fat
      derived cytokines, there have been no comprehensive analyses of the circadian
      clock machinery in adipose depots. In this study, we show robust and coordinated
      expression of circadian oscillator genes (Npas2, Bmal1, Per1-3, and Cry1-2) and
      clock-controlled downstream genes (Rev-erb alpha, Rev-erb beta, Dbp, E4bp4,
      Stra13, and Id2) in murine brown, inguinal, and epididymal (BAT, iWAT, and eWAT)
      adipose tissues. These results correlated with respective gene expression in
      liver and the serum markers of circadian function. Through Affymetrix microarray
      analysis, we identified 650 genes that shared circadian expression profiles in
      BAT, iWAT, and liver. Furthermore, we have demonstrated that temporally
      restricted feeding causes a coordinated phase-shift in circadian expression of
      the major oscillator genes and their downstream targets in adipose tissues. The
      presence of circadian oscillator genes in fat has significant metabolic
      implications, and their characterization may have potential therapeutic relevance
      with respect to the pathogenesis and treatment of diseases such as obesity, type
      2 diabetes, and the metabolic syndrome.

PMID- 16567518
TI  - Combined interleukin-6 and interleukin-1 deficiency causes obesity in young mice.
AB  - Proinflammatory cytokines including interleukin (IL)-1 and IL-6 exert pleiotropic
      effects on the neuro-immuno-endocrine system. Previously, we showed that IL-1
      receptor antagonist-deficient (IL-1Ra(-/-)) mice show a lean phenotype due to an
      abnormal lipid metabolism. On the contrary, it was reported that IL-6(-/-) mice
      exhibit obesity after 6 months of age. This study sought to assess the roles of
      IL-1 and IL-6 in body weight homeostasis. We generated mice deficient in IL-6 and
      IL-1Ra (IL-6(-/-) IL-1Ra(-/-)) and IL-6, IL-1alpha, and IL-1beta (IL-6(-/-) IL-1(
      /-)). IL-6(-/-) IL-1Ra(-/-) mice exhibited a lean phenotype, similar to IL-1Ra(-/
      ) mice. On the other hand, IL-6(-/-) IL-1(-/-) mice became obese as early as 10
      weeks of age, while IL-1(-/-) mice and IL-6(-/-) mice were normal at this age.
      The daily food intake was significantly higher in IL-6(-/-) IL-1(-/-) mice than
      in IL-6(-/-) IL-1(+/-) mice, while energy expenditure was comparable in these two
      strains. Acute anorexia induced by peripheral administration of IL-1 was
      significantly suppressed in IL-6(-/-) IL-1(-/-) mice, but not in IL-1(-/-) mice
      or IL-6(-/-) mice compared with wild-type mice. These results indicate that IL-1
      and IL-6 are both involved in the regulation of body fat in a redundant manner in
      young mice.

PMID- 16567519
TI  - Gonadal hormones determine sensitivity to central leptin and insulin.
AB  - Males have proportionally more visceral fat and are more likely to develop
      complications associated with obesity than females, and the male brain is
      relatively more sensitive to the catabolic action of insulin and less sensitive
      to that of leptin than the female brain. To understand the underlying mechanism,
      we manipulated estrogen through ovariectomy (OVX) and estradiol administration.
      Rats with relatively high systemic estrogen (intact females and OVX females and
      males administered estrogen subcutaneously) were significantly more sensitive to
      leptin's anorexic action in the brain (i3vt), as well as significantly less
      sensitive to insulin's i3vt action, than intact males. Administering estradiol
      directly into the brain of our females increased i3vt leptin sensitivity while
      decreasing i3vt insulin sensitivity and changed the body fat distribution of our
      females to resemble that of intact females. These data indicate that estrogen
      acts within the brain to increase leptin sensitivity, decrease insulin
      sensitivity, and favor subcutaneous over visceral fat.

PMID- 16567520
TI  - Evidence from glut2-null mice that glucose is a critical physiological regulator
      of feeding.
AB  - A role for glucose in the control of feeding has been proposed, but its precise
      physiological importance is unknown. Here, we evaluated feeding behavior in glut2
      null mice, which express a transgenic glucose transporter in their beta-cells to
      rescue insulin secretion (ripglut1;glut2-/- mice). We showed that in the absence
      of GLUT2, daily food intake was increased and feeding initiation and termination
      following a fasting period were abnormal. This was accompanied by suppressed
      regulation of hypothalamic orexigenic and anorexigenic neuropeptides expression
      during the fast-to-refed transition. In these conditions, however, there was
      normal regulation of the circulating levels of insulin, leptin, or glucose but a
      loss of regulation of plasma ghrelin concentrations. To evaluate whether the
      abnormal feeding behavior was due to suppressed glucose sensing, we evaluated
      feeding in response to intraperitoneal or intracerebroventricular glucose or 2
      deoxy-D-glucose injections. We showed that in GLUT2-null mice, feeding was no
      longer inhibited by glucose or activated by 2-deoxy-D-glucose injections and the
      regulation of hypothalamic neuropeptide expression by intracerebroventricular
      glucose administration was lost. Together, these data demonstrate that absence of
      GLUT2 suppressed the function of central glucose sensors, which control feeding
      probably by regulating the hypothalamic melanocortin pathway. Furthermore,
      inactivation of these glucose sensors causes overeating.

PMID- 16567521
TI  - Decreased in vitro type 1 immune response against coxsackie virus B4 in children
      with type 1 diabetes.
AB  - Enteroviruses, particularly Coxsackie virus B4 (CVB4), are considered to be
      involved in the pathogenesis of type 1 diabetes. We wanted to compare the
      characteristics of T-cell immune response to CVB4 in children with type 1
      diabetes and healthy children with and without HLA risk-associated haplotypes
      (HLA-DR3-DQ2 or HLA-DR4-DQ8) for type 1 diabetes. Peripheral blood mononuclear
      cells (PBMCs) were isolated and cultured with CVB4 and analyzed for cytokine and
      chemokine receptors by flow cytometry and for expression of transcription factors
      Tbet and GATA-3 by RT-PCR and Western blot. Culture supernatants were analyzed
      for secretion of gamma-interferon (IFN-gamma). In children with type 1 diabetes,
      a decreased percentage of T-cells expressed CCR2, CXCR6, interleukin (IL)-18R,
      and IL-12Rbeta2-chain after in vitro stimulation with CVB4 in comparison with
      healthy children with or without HLA risk genotype. Moreover, we found that
      children with type 1 diabetes had decreased IFN-gamma secretion and expression of
      Tbet, both on mRNA and protein level, in CVB4-stimulated PBMCs. Accordingly,
      children with type 1 diabetes show an impaired type 1 immune response against
      CVB4 compared with healthy children. This may lead to a delayed clearance of the
      virus and, at least partly, explain why children with type 1 diabetes may be more
      prone to CVB4 infections and related complications, such as beta-cell damage.

PMID- 16567522
TI  - Atorvastatin fails to prevent the development of autoimmune diabetes despite
      inhibition of pathogenic beta-cell-specific CD8 T-cells.
AB  - Statins, the widely used inhibitors of cholesterol biosynthesis, also have
      immunomodulatory properties. Statins have recently been shown to have beneficial
      prophylactic and therapeutic effects in actively induced, short-term animal
      models of the autoimmune diseases multiple sclerosis and rheumatoid arthritis,
      leading to clinical trials. We therefore investigated whether statins' protective
      effects could be reproduced in the nonobese diabetic (NOD) mouse, a spontaneous,
      chronic model of autoimmune diabetes. Mice were treated with 0, 1, 10, or 50 mg x
      kg(-1) x day(-1) oral atorvastatin from 6 or 12 weeks of age, without effect on
      the rate or prevalence of diabetes development, islet infiltration, or islet
      major histocompatibility complex class II expression. However, there was clear
      evidence of a disease-relevant immunological effect of statins in vivo, since
      short-term (12-day) treatment significantly reduced the number of proinflammatory
      (gamma-interferon-producing) CD8 cells recognizing a dominant pathogenic epitope.
      This effect was absent in mice treated for longer periods, suggesting that
      atorvastatin loses efficiency in inhibiting autoantigen-specific T-cells over
      time. This observation may explain the discrepancy between the reported success
      of statins in acutely induced models and the lack of it in a chronic, spontaneous
      model of autoimmune disease and has implications for the adoption of such therapy
      in humans.

PMID- 16567523
TI  - CD4+ CD25+ regulatory T-cells inhibit the islet innate immune response and
      promote islet engraftment.
AB  - Early islet cell loss is a significant problem in clinical islet cell
      transplantation. Diverse stress stimuli induce innate immune responses in islets
      that contribute to beta-cell dysfunction, inflammation, and loss. Here, we show
      that cytokine-stimulated murine islets express multiple inflammatory chemokines
      that recruit T-cells and thereby impair islet function in vitro and in vivo. Both
      nonislet ductal and exocrine elements and the individual islet cellular
      components contribute to this innate immune response. CD4+ CD25+ regulatory T
      cells inhibit islet chemokine expression through a cell contact-dependent,
      soluble factor-independent mechanism and inhibit effector T-cell migration to the
      islet. Regulatory T-cells can also migrate to stimulated islets. Cotransfer of
      regulatory T-cells with islets in a transplantation model prevents islet innate
      immune responses and inflammation and preserves normal architecture and
      engraftment. Regulatory T-cell inhibition of multiple components of innate immune
      responses may be a fundamental aspect of their function that influences ischemia
      reperfusion injury and adaptive immunity.

PMID- 16567525
TI  - Mechanisms of time-dependent potentiation of insulin release: involvement of
      nitric oxide synthase.
AB  - Time-dependent potentiation (TDP) of insulin release is normally absent in mice.
      However, we recently demonstrated that TDP occurs in mouse islets under
      conditions of forced decrease of intracellular pH (pH(i)) associated with
      elevated NADPH+H(+) (NADPH) levels. Hence, TDP in mouse islets may be kept
      suppressed by neuronal nitric oxide (NO) synthase (nNOS), an NADPH-utilizing
      enzyme with alkaline pH optimum. To determine the role of nNOS in the suppression
      of TDP in mouse islets, glucose-induced TDP was monitored in mouse islets in
      which nNOS activity had been genetically removed or chemically inhibited and
      compared with the TDP response in wild-type mouse islets with and without forced
      intracellular acidification. Genetic deletion of nNOS was provided by an nNOS
      knockout (NOS-KO) mouse model, B6-129S4-Nos1(tm1Plh)/J. To explore how nNOS
      inhibits TDP, we compared pH(i) and NADPH levels in wild-type and NOS-KO islets
      and monitored TDP with various components of the nNOS reaction added. Glucose
      normally does not produce TDP in wild-type mouse islets except under forced
      intracellular acidification. Remarkably, glucose produced strong TDP in NOS-KO
      islets and in wild-type islets treated with nNOS inhibitors. TDP in NOS-KO islets
      was not inhibited by the addition of NO, and NOS-KO islets exhibited a lower
      pH(i) than wild-type islets. The addition of arginine to wild-type islets also
      enabled glucose to induce TDP. Our results show that nNOS activity contributes to
      the absence of TDP in mouse islets putatively through depletion of intracellular
      arginine.

PMID- 16567524
TI  - Protection of INS-1 cells from free fatty acid-induced apoptosis by targeting
      hOGG1 to mitochondria.
AB  - Chronic exposure to elevated levels of free fatty acids (FFAs) impairs pancreatic
      beta-cell function and contributes to the decline of insulin secretion in type 2
      diabetes. Previously, we reported that FFAs caused increased nitric oxide (NO)
      production, which damaged mitochondrial DNA (mtDNA) and ultimately led to
      apoptosis in INS-1 cells. To firmly establish the link between FFA-generated
      mtDNA damage and apoptosis, we stably transfected INS-1 cells with an expression
      vector containing the gene for the DNA repair enzyme human 8-oxoguanine DNA
      glycosylase/apurinic lyase (hOGG1) downstream of the mitochondrial targeting
      sequence (MTS) from manganese superoxide dismutase. Successful integration of MTS
      OGG1 into the INS-1 cellular genome was confirmed by Southern blot analysis.
      Western blots and enzyme activity assays revealed that hOGG1 was targeted to
      mitochondria and the recombinant enzyme was active. MTS-OGG1 cells showed a
      significant decrease in FFA-induced mtDNA damage compared with vector-only
      transfectants. Additionally, hOGG1 overexpression in mitochondria decreased FFA
      induced inhibition of ATP production and protected INS-1 cells from apoptosis.
      These results indicate that mtDNA damage plays a pivotal role in FFA-induced beta
      cell dysfunction and apoptosis. Therefore, targeting DNA repair enzymes into beta
      cell mitochondria could be a potential therapeutic strategy for preventing or
      delaying the onset of type 2 diabetes symptoms.

PMID- 16567527
TI  - Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a
      cAMP-dependent protein kinase pathway.
AB  - Although genistein, a soy isoflavone, has beneficial effects on various tissues,
      it is unclear whether it plays a role in physiological insulin secretion. Here,
      we present evidence that genistein increases rapid glucose-stimulated insulin
      secretion (GSIS) in both insulin-secreting cell lines (INS-1 and MIN6) and mouse
      pancreatic islets. Genistein elicited a significant effect at a concentration as
      low as 10 nmol/l with a maximal effect at 5 micromol/l. The effect of genistein
      on GSIS was not dependent on estrogen receptor and also not related to an
      inhibition of protein tyrosine kinase (PTK). Consistent with its effect on GSIS,
      genistein increases intracellular cAMP and activates protein kinase A (PKA) in
      both cell lines and the islets by a mechanism that does not involve estrogen
      receptor or PTK. The induced cAMP by genistein, at physiological concentrations,
      may result primarily from enhanced adenylate cyclase activity. Pharmacological or
      molecular intervention of PKA activation indicated that the insulinotropic effect
      of genistein is primarily mediated through PKA. These findings demonstrated that
      genistein directly acts on pancreatic beta-cells, leading to activation of the
      cAMP/PKA signaling cascade to exert an insulinotropic effect, thereby providing a
      novel role of soy isoflavones in the regulation of insulin secretion.

PMID- 16567526
TI  - Blockers of the delayed-rectifier potassium current in pancreatic beta-cells
      enhance glucose-dependent insulin secretion.
AB  - Delayed-rectifier K+ currents (I(DR)) in pancreatic beta-cells are thought to
      contribute to action potential repolarization and thereby modulate insulin
      secretion. The voltage-gated K+ channel, K(V)2.1, is expressed in beta-cells, and
      the biophysical characteristics of heterologously expressed channels are similar
      to those of I(DR) in rodent beta-cells. A novel peptidyl inhibitor of
      K(V)2.1/K(V)2.2 channels, guangxitoxin (GxTX)-1 (half-maximal concentration
      approximately 1 nmol/l), has been purified, characterized, and used to probe the
      contribution of these channels to beta-cell physiology. In mouse beta-cells, GxTX
      1 inhibits 90% of I(DR) and, as for K(V)2.1, shifts the voltage dependence of
      channel activation to more depolarized potentials, a characteristic of gating
      modifier peptides. GxTX-1 broadens the beta-cell action potential, enhances
      glucose-stimulated intracellular calcium oscillations, and enhances insulin
      secretion from mouse pancreatic islets in a glucose-dependent manner. These data
      point to a mechanism for specific enhancement of glucose-dependent insulin
      secretion by applying blockers of the beta-cell I(DR), which may provide
      advantages over currently used therapies for the treatment of type 2 diabetes.

PMID- 16567528
TI  - Postprandial suppression of glucagon secretion depends on intact pulsatile
      insulin secretion: further evidence for the intraislet insulin hypothesis.
AB  - Type 2 diabetes is characterized by an approximately 60% loss of beta-cell mass,
      a marked defect in postprandial insulin secretion, and a failure to suppress
      postprandial glucagon concentrations. It is possible that postprandial
      hyperglucagonemia in type 2 diabetes is due to impaired postprandial insulin
      secretion. To address this, we studied eight adult Goettingen minipigs before and
      after an approximately 60% reduction in beta-cell mass induced by alloxan. Pigs
      were studied fasting and after ingestion of a mixed meal. Insulin and glucagon
      secretion were determined by deconvolution of blood hormone concentrations
      measured at 1-min intervals. The relationship between insulin and glucagon
      release was analyzed using cross-correlation and forward versus reverse cross
      approximate entropy. We report that glucagon and insulin were secreted in
      approximately 4-min pulses. Prealloxan, postprandial insulin secretion drove an
      approximately 20% suppression of glucagon concentrations (P < 0.01), through
      inhibition of glucagon pulse mass. The alloxan-induced approximately 60% deficit
      in beta-cell mass lead to an approximately 70% deficit in postprandial insulin
      secretion and loss of the postprandial insulin-driven suppression of glucagon
      secretion. We conclude that postprandial hyperglucagonemia in type 2 diabetes is
      likely due to loss of intraislet postprandial suppression of glucagon secretion
      by insulin.

PMID- 16567529
TI  - Sustained exposure to high glucose concentrations modifies glucose signaling and
      the mechanics of secretory vesicle fusion in primary rat pancreatic beta-cells.
AB  - The mechanism(s) by which chronic hyperglycemia impairs glucose-stimulated
      insulin secretion is poorly defined. Here, we compare the "nanomechanics" of
      single exocytotic events in primary rat pancreatic beta-cells cultured for 48 h
      at optimal (10 mmol/l) or elevated (30 mmol/l) glucose concentrations. Cargo
      release was imaged by total internal reflection fluorescence microscopy of lumen
      targeted probes (neuropeptide Y [NPY]-pH-insensitive yellow fluorescent protein
      [NPY-Venus] or NPY-monomeric red fluorescent protein), while the fate of the
      vesicle membrane was reported simultaneously with phosphatase-on-the-granule-of
      insulinoma-enhanced green fluorescent protein. Under all conditions studied,
      exocytosis proceeded via a "cavity recapture" mechanism in which the vesicle and
      plasma membranes fused transiently. While essentially complete release of NPY
      Venus was observed in 24 +/- 1% of glucose-stimulated exocytotic events in cells
      maintained at 10 mmol/l glucose, this value was reduced reversibly to 5 +/- 2% of
      events by culture at 30 mmol/l glucose, in line with decreases in Glut2 and
      glucokinase gene expression, and attenuated glucose-stimulated increases in NADPH
      and intracellular [Ca2+]. Since vesicle release in response to cell
      depolarization with KCl was not affected by culture at 30 mmol/l glucose, we
      conclude that hyperglycemia causes the abnormal termination of individual insulin
      release events principally by inhibiting glucose signaling.

PMID- 16567531
TI  - Coordinate changes in plasma glucose and pancreatic beta-cell function in Latino
      women at high risk for type 2 diabetes.
AB  - The purpose of this study was to examine longitudinally the relationship among
      glucose levels, pancreatic beta-cell function, and insulin resistance in women at
      high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and
      intravenous glucose tolerance tests (IVGTTs) were performed at 15-month intervals
      for up to 5 years or until fasting plasma glucose exceeded 140 mg/dl in Hispanic
      women with recent gestational diabetes. Data were analyzed 1) to compare changes
      in insulin sensitivity, beta-cell function, and glucose levels between women who
      had diabetes at one or more visits and women who remained diabetes free and 2) to
      determine longitudinal patterns of change in glucose levels and acute beta-cell
      compensation for insulin resistance. Seventy-one women provided data from a total
      of 280 paired OGTTs and IVGTTs during a median follow-up of 46 months. Compared
      with the 47 women who remained free of diabetes, the 24 who either had diabetes
      (n = 9) or developed it during follow-up (n = 15) had higher baseline glucose
      levels and lower acute beta-cell compensation for insulin resistance. Baseline
      insulin sensitivity was low in both groups and did not change significantly
      during follow-up. Fasting and 2-h glucose levels increased more rapidly in the
      diabetic group despite a decline in acute beta-cell compensation that was
      significantly slower than the decline in women who did not develop diabetes. This
      paradox was explained by an accelerated rise in glucose levels for any decline in
      beta-cell compensation when beta-cell compensation reached approximately 10% of
      normal, a level that was reached in the women who had or developed diabetes but
      not in the women who remained diabetes free. These findings define a pathogenesis
      for type 2 diabetes in one high-risk group that is characterized by a relatively
      long-term decline in acute beta-cell compensation for chronic insulin resistance
      that is attended by slowly rising glucose levels. Only relatively late in this
      process do glucose levels rise rapidly and into the diabetic range.

PMID- 16567530
TI  - Inhibition of glucose-stimulated activation of extracellular signal-regulated
      protein kinases 1 and 2 by epinephrine in pancreatic beta-cells.
AB  - Glucose sensing is essential for the ability of pancreatic beta-cells to produce
      insulin in sufficient quantities to maintain blood glucose within the normal
      range. Stress causes the release of adrenergic hormones that increase circulating
      glucose by promoting glucose production and inhibiting insulin release. We have
      shown that extracellular signal-regulated kinases 1 and 2 (ERK1/2) are responsive
      to glucose in pancreatic beta-cells and that glucose activates ERK1/2 by
      mechanisms independent of insulin. Here we show that glucose-induced activation
      of ERK1/2 is inhibited by epinephrine through the alpha2-adrenergic receptor.
      Epinephrine and the selective alpha2-adrenergic agonist UK14304 reduced insulin
      secretion and glucose-stimulated ERK1/2 activation in a pertussis toxin-sensitive
      manner, implicating the alpha subunit of a Gi family member. Alpha2-adrenergic
      agonists also reduced stimulation of ERK1/2 by glucagon-like peptide 1 and KCl,
      but not by phorbol ester or nerve growth factor. Our findings suggest that alpha2
      adrenergic agonists act via a Gi family member on early steps in ERK1/2
      activation, supporting the idea that ERK1/2 are regulated in a manner that
      reflects insulin demand.

PMID- 16567532
TI  - Blockade of GABA(A) receptors in the ventromedial hypothalamus further stimulates
      glucagon and sympathoadrenal but not the hypothalamo-pituitary-adrenal response
      to hypoglycemia.
AB  - Hypoglycemia provokes a multifaceted counterregulatory response involving the
      sympathoadrenal system, stimulation of glucagon secretion, and the hypothalamo
      pituitary-adrenal axis that is commonly impaired in diabetes. We examined whether
      modulation of inhibitory input from gamma-aminobutyric acid (GABA) in the
      ventromedial hypothalamus (VMH), a major glucose-sensing region within the brain,
      plays a role in affecting counterregulatory responses to hypoglycemia. Normal
      Sprague-Dawley rats had carotid artery and jugular vein catheters chronically
      implanted, as well as bilateral steel microinjection guide cannulas inserted down
      to the level of the VMH. Seven to 10 days following surgery, the rats were
      microinjected with artificial extracellular fluid, the GABA(A) receptor agonist
      muscimol (1 nmol/side), or the GABA(A) receptor antagonist bicuculline methiodide
      (12.5 pmol/side) before being subjected to a hyperinsulinemic-hypoglycemic (2.5
      mmol/l) glucose clamp for 90 min. Following VMH administration of bicuculline
      methiodide, glucose infusion rates were significantly suppressed, whereas
      muscimol raised glucose infusion rates significantly compared with controls.
      Glucagon and epinephrine responses were elevated with the antagonist and
      suppressed with the agonist compared with controls. Corticosterone responses,
      however, were unaffected by either administration of the agonist or antagonist
      into the VMH. These data demonstrate that modulation of the GABAergic system in
      the VMH alters both glucagon and sympathoadrenal, but not corticosterone,
      responses to hypoglycemia. Our findings are consistent with the hypothesis that
      GABAergic inhibitory tone within the VMH can modulate glucose counterregulatory
      responses.

PMID- 16567533
TI  - Cognitive and neural hippocampal effects of long-term moderate recurrent
      hypoglycemia.
AB  - Recurrent hypoglycemia is the most feared complication of intensive insulin
      therapy for type 1 diabetes. Study of the cognitive impact of recurrent
      hypoglycemia in humans has been hampered by difficulty in controlling for prior
      glycemic history and diabetes status; there have been no prospective studies. We
      used a rat model of recurrent hypoglycemia with hypoglycemia for 3 h, once
      weekly, from 1 month of age. At 4, 8, and 12 months of age, cohorts were tested
      on a hippocampally dependent spatial memory task, during which hippocampal
      extracellular fluid (ECF) glucose and lactate were measured using microdialysis.
      At 4 months, recurrent hypoglycemia improved euglycemic task performance (76 +/-
      4 vs. 64 +/- 3% for controls) and reversed the task-associated dip in ECF glucose
      seen in controls. However, recurrent hypoglycemia impaired performance in animals
      tested when hypoglycemic (45 +/- 4 vs. 55 +/- 2%). Recurrent hypoglycemia
      preserved euglycemic task performance across age: at 12 months, both task
      performance (62%) and ECF glucose changes in euglycemic recurrently hypoglycemic
      animals resembled those of 4-month-old control animals, whereas control animals'
      performance deteriorated to chance (44%) by 8 months. At 12 months, hippocampal
      slice physiology was assessed, with results paralleling the cognitive findings:
      slices from recurrently hypoglycemic rats showed improved gamma-aminobutyric acid
      (GABA)ergic inhibition at euglycemia but much greater loss of this tone at low
      bath glucose. Our data show that moderate weekly hypoglycemia prevented age
      related decline in hippocampally cognitive function and cognitive metabolism, at
      least when euglycemic. The impact of recurrent hypoglycemia on cognition is
      multifaceted and includes both metabolic and electrophysiological components.

PMID- 16567534
TI  - Survival benefits of intensive insulin therapy in critical illness: impact of
      maintaining normoglycemia versus glycemia-independent actions of insulin.
AB  - Tight blood glucose control with insulin reduces morbidity and mortality of
      critically ill patients. However, the relative impact of maintaining
      normoglycemia and of glycemia-independent actions of insulin remains unknown. We
      therefore independently manipulated blood glucose and plasma insulin levels in
      burn-injured, parentally fed rabbits over 7 days to obtain four study groups: two
      normoglycemic groups with either normal or elevated insulin levels and two
      hyperglycemic groups with either normal or elevated insulin levels. We studied
      the relative impact of glycemia and glycemia-independent effects of insulin on
      survival; myocardial contractility in an open chest preparation; endothelial
      function in isolated aortic rings; and liver, kidney, and leukocyte function in a
      rabbit model of critical illness. Mortality was significantly lower in the two
      normoglycemic groups independent of insulin levels. Maintaining normoglycemia,
      independent of insulin levels, prevented endothelial dysfunction as well as liver
      and kidney injury. To increase myocardial systolic function, elevated insulin
      levels and prevention of hyperglycemia were required concomitantly. Leukocyte
      dysfunction was present in the two hyperglycemic groups, which could in part be
      rescued by insulin. The results suggest that the observed benefits of intensive
      insulin therapy required mainly maintenance of normoglycemia; whereas glycemia
      independent actions of insulin exerted only minor, organ-specific impact.

PMID- 16567535
TI  - Brain magnetic resonance imaging correlates of impaired cognition in patients
      with type 2 diabetes.
AB  - The structural correlates of impaired cognition in type 2 diabetes are unclear.
      The present study compared cognition and brain magnetic resonance imaging (MRI)
      between type 2 diabetic patients and nondiabetic control subjects and assessed
      the relationship between cognition and MRI findings and blood pressure and
      metabolic control. The study included 113 patients and 51 control subjects. Brain
      MRI scans were rated for white matter lesions (WMLs), cortical and subcortical
      atrophy, and infarcts. Neuropsychological test scores were divided into five
      cognitive domains and expressed as standardized Z values. Type 2 diabetes was
      associated with deep WMLs (P = 0.02), cortical (P < 0.001) and subcortical (P <
      0.05) atrophy, (silent) infarcts (P = 0.06), and impaired cognitive performance
      (attention and executive function, information-processing speed, and memory, all
      P < 0.05). Adjustment for hypertension did not affect the results. Within the
      type 2 diabetic group, cognitive function was inversely related with WMLs,
      atrophy, and the presence of infarcts (adjusted for age, sex, and estimated IQ),
      and there was a modest association with HbA1c and diabetes duration. This
      association was strongest for age, even more so than in control subjects. We
      conclude that cognitive impairments in patients with type 2 diabetes are not only
      associated with subcortical ischemic changes in the brain, but also with
      increased brain atrophy.

PMID- 16567536
TI  - The natural course of beta-cell function in nondiabetic and diabetic individuals:
      the Insulin Resistance Atherosclerosis Study.
AB  - Data from the UKPDS (U.K. Prospective Diabetes Study) indicate a continuous
      decline in beta-cell function in patients with type 2 diabetes. We studied
      longitudinal changes in beta-cell function (follow-up of 5.2 years) in subjects
      with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2
      diabetes, using acute insulin response (AIR) and insulin sensitivity index (S(i))
      from a frequently sampled intravenous glucose tolerance test among African
      American, Hispanic, and non-Hispanic white subjects aged 40-69 years. At
      baseline, decreasing levels of both S(i) and AIR (either unadjusted or adjusted
      for S(i)) mirrored deteriorating glucose tolerance status at baseline and at
      follow-up. A different pattern was found with respect to longitudinal changes;
      S(i) declined in each glucose tolerance category, ranging from -0.81 x10(-4) min(
      1) x muU(-1) x ml(-1) in NGT at baseline and NGT at follow-up (NGT/NGT) to -1.06
      x10(-4) in NGT/diabetes, whereas the directional change in AIR principally
      determined the glucose tolerance status at follow-up. In NGT/NGT S(i) decreased
      by 35% and AIR increased by 34%. Results were similar in each of the three ethnic
      groups. These data shed light on the natural course of beta-cell function; over
      5.2 years, mean insulin sensitivity declined in each glucose tolerance category.
      The change in AIR, however, principally determined glucose tolerance status at
      follow-up; NGT was maintained by a compensatory increase in insulin secretion.
      Failure to increase insulin secretion led to IGT, and a decrease in insulin
      secretion led to overt diabetes. This data may have important implications for
      the prevention and treatment of type 2 diabetes.

PMID- 16567537
TI  - Antecedent hypercortisolemia is not primarily responsible for generating
      hypoglycemia-associated autonomic failure.
AB  - Hypoglycemia-associated autonomic failure (HAAF) occurs commonly in patients with
      longstanding diabetes, placing affected patients at increased risk for severe
      hypoglycemia. Previous studies have suggested that hypoglycemia-induced
      hypercortisolemia may be responsible for blunting subsequent sympathoadrenal
      responses to hypoglycemia; however, this view remains highly controversial. In
      this work, we sought to better define the role of antecedent hypercortisolemia in
      generating HAAF, using two complimentary experimental models in nondiabetic human
      subjects: 1) antecedent hydrocortisone infusions (simulating physiologic cortisol
      responses to hypoglycemia) and 2) antecedent hypoglycemia, with and without
      concurrent blockade of endogenous cortisol production using oral metyrapone. Our
      results showed no effect of antecedent hypercortisolemia on epinephrine responses
      to subsequent hypoglycemia (area under the curve/time 280 +/- 53 vs. 337 +/- 57
      pg/ml, P = 0.16). Of particular importance, selective blockade of endogenous
      cortisol production during antecedent hypoglycemia had no effect on subsequent
      counterregulatory responses to hypoglycemia. Compared with epinephrine responses
      following antecedent euglycemia (area under the curve/time 312 +/- 38 pg/ml),
      epinephrine responses were comparably blunted following antecedent hypoglycemia,
      regardless of whether concurrent metyrapone blockade was employed (198 +/- 28 vs.
      192 +/- 28 pg/ml, P = NS). Similar results were obtained for glucagon and ACTH
      levels. Considered together, these observations provide strong evidence that
      hypoglycemia-induced hypercortisolemia is not primarily responsible for the
      generation of HAAF.

PMID- 16567538
TI  - Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes.
AB  - Chronic hyperglycemia underlies microvascular complications in patients with type
      1 diabetes. The mechanisms leading to these vascular complications are not fully
      understood. Recently, we observed that acute hyperglycemia results in endothelial
      glycocalyx damage. To establish whether glycocalyx is associated with
      microvascular damage, we performed glycocalyx perturbation volume measurements in
      type 1 diabetic patients with microalbuminuria (DM1-MA group; n = 7), without
      microalbuminuria (DM1-NA group; n = 7), and in age-matched control subjects (CON;
      n = 7). Systemic glycocalyx volume was determined comparing intravascular
      distribution volume of a glycocalyx-permeable tracer (dextran 40) to that of a
      glycocalyx-impermeable tracer (labeled erythrocytes). Sublingual capillaries were
      visualized using orthogonal polarization spectral microscopy to estimate
      microvascular glycocalyx. Patients and control subjects were matched according to
      age and BMI. Glycocalyx volume decreased in a stepwise fashion from CON, DM1-NA,
      and finally DM1-MA subjects (1.5 +/- 0.1, 0.8 +/- 0.4, and 0.2 +/- 0.1 l,
      respectively, P < 0.05). Microvascular glycocalyx in sublingual capillaries was
      also decreased in type 1 diabetes versus the control group (0.5 +/- 0.1 vs. 0.9
      +/- 0.1 microm, P < 0.05). Plasma hyaluronan, a principal glycocalyx constituent,
      and hyaluronidase were increased in type 1 diabetes. In conclusion, type 1
      diabetic patients are characterized by endothelial glycocalyx damage, the
      severity of which is increased in presence of microalbuminuria.

PMID- 16567539
TI  - Clustering of insulin resistance with vascular dysfunction and low-grade
      inflammation in type 2 diabetes.
AB  - Vascular dysfunction, low-grade inflammation, insulin resistance, and impaired
      fibrinolysis have each been reported to be present in type 2 diabetes, but their
      relationships, and the role of obesity, have not been investigated. We measured
      insulin sensitivity (euglycemic clamp), forearm blood flow responses to graded
      local acetylcholine (Ach) and sodium nitroprusside (SNP) infusions, plasma
      concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, von
      Willebrand factor (vWF), plasminogen activator inhibitor (PAI)-1, tissue
      plasminogen activator (tPA), and high-sensitivity C-reactive protein (hs-CRP) in
      81 diabetic patients. When patients were stratified by insulin resistance, more
      severe insulin resistance was associated (P < 0.05) with overweight, central fat
      distribution, hypertension, and dyslipidemia (with similar sex distribution, age,
      fasting plasma glucose, and HbA1c). With regard to vascular function, both
      endothelium-dependent (Ach) (-22, -40, and -52%; P < 0.0001) and -independent
      (SNP) (-3, -7, and -27%; P < 0.02) vasodilatation were progressively reduced
      across insulin resistance tertiles. In multivariate analysis, inflammatory
      markers (IL-6, hs-CRP, and TNF-alpha) were independently associated with insulin
      resistance and fasting glycemia, fibrinolytic markers PAI-1 and tPA with insulin
      resistance and central fat distribution, and vascular indexes (vWF, Ach, and SNP
      vasodilation) with insulin resistance and obesity or cytokines (TNF-alpha or IL
      6). In type 2 diabetes, insulin resistance is associated with vascular
      dysfunction/damage, impaired fibrinolysis, and low-grade inflammation
      independently of obesity and poor glycemic control.

PMID- 16567540
TI  - Insulin treatment ameliorates impaired corneal reepithelialization in diabetic
      rats.
AB  - Patients with diabetes are at an increased risk for developing corneal disorders,
      often as a result of surgical and nonsurgical trauma. This study investigated
      whether intensive treatment of diabetes with the goal of maintaining blood
      glucose concentrations close to the normal range could ameliorate the delayed
      corneal wound healing found in animals with uncontrolled diabetes. Diabetes was
      induced with streptozotocin, and rats were divided into groups based on the
      degree of blood glucose control: 1) not treated with insulin implants (DB group),
      2) receiving insulin implants and determined to be normoglycemic (DB-IN group),
      and 3) normal, nondiabetic animals serving as controls. Immediately before
      wounding at 9 or 11 weeks after the induction of the diabetic state, corneal
      thickness and corneal sensitivity of the DB and DB-IN groups were comparable with
      controls. DB, but not DB-IN, rats exhibited subnormal intraocular pressure. At 9
      and 11 weeks after the onset of diabetes, the corneas of the right and left eyes,
      respectively, were abraded by mechanical scraping. The DB rats had residual
      corneal epithelial defects that ranged from 23% to 5.6-fold larger compared with
      the control group and a rate of healing that was 19% slower than control animals.
      The DB-IN group had healing characteristics similar to the control group. DNA
      synthesis in the peripheral cornea and conjunctiva, but not the limbus, of DB
      animals was reduced 50 and 91%, respectively, from control levels. Cell
      proliferation in the DB-IN group was comparable with the control group, with the
      exception of a 72% increase in the peripheral cornea in the DB-IN group. These
      results indicate that intensive therapy with insulin, which establishes
      normoglycemia in rats with diabetes, prevents the delay in wound healing of
      ocular surface epithelium observed in poorly controlled diabetic animals.

PMID- 16567541
TI  - Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic
      and local insulin.
AB  - Diabetic retinopathy is characterized by early onset of neuronal cell death. We
      previously showed that insulin mediates a prosurvival pathway in retinal neurons
      and that normal retina expresses a highly active basal insulin receptor/Akt
      signaling pathway that is stable throughout feeding and fasting. Using the
      streptozotocin-induced diabetic rat model, we tested the hypothesis that diabetes
      diminishes basal retinal insulin receptor signaling concomitantly with increased
      diabetes-induced retinal apoptosis. The expression, phosphorylation status,
      and/or kinase activity of the insulin receptor and downstream signaling proteins
      were investigated in retinas of age-matched control, diabetic, and insulin
      treated diabetic rats. Four weeks of diabetes reduced basal insulin receptor
      kinase, insulin receptor substrate (IRS)-1/2-associated phosphatidylinositol 3
      kinase, and Akt kinase activity without altering insulin receptor or IRS-1/2
      expression or tyrosine phosphorylation. After 12 weeks of diabetes, constitutive
      insulin receptor autophosphorylation and IRS-2 expression were reduced, without
      changes in p42/p44 mitogen-activated protein kinase or IRS-1. Sustained systemic
      insulin treatment of diabetic rats prevented loss of insulin receptor and Akt
      kinase activity, and acute intravitreal insulin administration restored insulin
      receptor kinase activity. Insulin treatment restored insulin receptor-beta
      autophosphorylation in rat retinas maintained ex vivo, demonstrating functional
      receptors and suggesting loss of ligand as a cause for reduced retinal insulin
      receptor/Akt pathway activity. These results demonstrate that diabetes
      progressively impairs the constitutive retinal insulin receptor signaling pathway
      through Akt and suggests that loss of this survival pathway may contribute to the
      initial stages of diabetic retinopathy.

PMID- 16567543
TI  - Genetic and functional analysis of the Nkt1 locus using congenic NOD mice:
      improved Valpha14-NKT cell performance but failure to protect against type 1
      diabetes.
AB  - Defective invariant natural killer T-cells (iNKT cells) have been implicated in
      the etiology of type 1 diabetes in nonobese diabetic (NOD) mice. In a genome scan
      of a cross between NOD and C57BL/6 mice, the most significant locus controlling
      the number of iNKT cells, referred to as Nkt1, was recently mapped to distal
      chromosome 1. Here, using congenic mice for this chromosomal segment, we
      definitively demonstrate the existence of Nkt1 and show that introgression of the
      C57BL/6 allele onto the NOD background improves both the number of iNKT cells and
      their rapid production of cytokines elicited by alpha-galactosylceramide
      treatment, explaining at least half of the difference between the NOD and C57BL/6
      strains. Using new subcongenic lines, we circumscribed the Nkt1 locus to a 8.7-cM
      segment, between the NR1i3 and D1Mit458 markers, that notably includes the SLAM
      (signaling lymphocytic activation molecule) gene cluster, recently involved in
      murine lupus susceptibility. However, despite a significant correction of the
      iNKT cell defect, the Nkt1 locus did not alter the course of spontaneous diabetes
      in congenic mice. Our findings indicate a complex relationship between iNKT cells
      and autoimmune susceptibility. Congenic lines nonetheless provide powerful models
      to dissect the biology of iNKT cells.

PMID- 16567542
TI  - The PPARG Pro12Ala polymorphism is associated with a decreased risk of developing
      hyperglycemia over 6 years and combines with the effect of the APM1 G-11391A
      single nucleotide polymorphism: the Data From an Epidemiological Study on the
      Insulin Resistance Syndrome (DESIR) study.
AB  - Although cross-sectional studies have associated the Pro12Ala polymorphism of
      PPARG with type 2 diabetes, prospective studies offer more opportunities to
      investigate genetic variants. Associations between PPARG polymorphisms with
      insulin resistance parameters and with the 6-year incidence of impaired fasting
      glucose or type 2 diabetes were tested in 3,914 French Caucasians from the DESIR
      (Data From an Epidemiological Study on the Insulin Resistance Syndrome) cohort.
      In subjects normoglycemic at baseline (n = 3,498), the 6-year risk of
      hyperglycemia was lower in PPARG Ala carriers (odds ratio [OR] vs. ProPro = 0.66
      [95% CI 0.44-0.99], P = 0.046 adjusted for sex, age, and BMI). Similar results
      were found with the PPARG C1431T single nucleotide polymorphism (SNP; adjusted OR
      = 0.65 [0.44-0.96], P = 0.036). Both alleles are in strong linkage disequilibrium
      (D' = 0.669, P < 0.001). The baseline mean fasting insulin and homeostasis model
      assessment of insulin resistance (HOMA-IR) were lower in Ala carriers compared
      with ProPro homozygotes (P = 0.001 for both), with smaller increases in mean
      insulin and HOMA-IR during follow-up (P = 0.007 and 0.018, respectively). No
      association with insulin levels or HOMA-IR was found with C1431T. In this cohort,
      the APM1 G-11391A SNP is associated with the development of hyperglycemia. The
      combined effects of PPARG Pro12Ala and APM1 G-11391A SNPs showed no interaction
      on the risk of 6-year hyperglycemia. The PPARG Ala allele showed a relatively
      high protective effect in developing hyperglycemia and hyperinsulinemia during a
      6-year period. Cumulative rather than synergistic effects of PPARG Pro12Ala and
      APM1 SNPs on diabetes risk are suggested.

PMID- 16567544
TI  - EIF4A2 is a positional candidate gene at the 3q27 locus linked to type 2 diabetes
      in French families.
AB  - One of the most replicated loci influencing type 2 diabetes-related quantitative
      traits (quantitative trait loci [QTL]) is on chromosome 3q27 and modulates both
      type 2 diabetes-and metabolic syndrome-associated phenotypes. A QTL for type 2
      diabetes age of onset (logarithm of odds [LOD] score = 3.01 at D3S3686, P =
      0.0001) was identified in a set of French families. To assess genetic variation
      underlying both age-of-onset QTL and our previous type 2 diabetes linkage in a
      3.87-Mb interval, we explored 36 single nucleotide polymorphisms (SNPs) in two
      biologically relevant candidate genes for glucose homeostasis, kininogen (KNG1),
      and eukaryotic translation initiation factor 4alpha2 (EIF4A2). Analysis of 148
      families showed significant association of a frequent SNP, rs266714, located 2.47
      kb upstream of EIF4A2, with familial type 2 diabetes (family-based association
      test, P = 0.0008) and early age of onset (P = 0.0008). This SNP also contributes
      to both age-of-onset QTL (1.13 LOD score decrease P = 0.02) and type 2 diabetes
      linkage (genotype identical-by-descent sharing test, P = 0.02). However, no
      association was observed in three independent European diabetic cohorts. EIF4A2
      controls specific mRNA translation and protein synthesis rate in pancreatic beta
      cells, and our data indicates that EIF4A2 is downregulated by high glucose in rat
      beta-INS832/13 cells. The potential role of EIF4A2 in glucose homeostasis and its
      putative contribution to type 2 diabetes in the presence of metabolic stress will
      require further investigation.

PMID- 16567545
TI  - Potential therapeutic gene for the treatment of ischemic disease: Ad2/hypoxia
      inducible factor-1alpha (HIF-1)/VP16 enhances B-type natriuretic peptide gene
      expression via a HIF-1-responsive element.
AB  - In this issue of Molecular Pharmacology, Luo et al. (p. 1953) present a study
      employing a HIF-1alpha/VP16 chimera to investigate the mechanism by which this
      constitutively active transcription factor activates expression of brain
      natriuretic peptide (BNP). The results define a functional hypoxia responsive
      element (HRE) in the promoter of the human BNP gene and demonstrate that this HRE
      is necessary for HIF-1alpha/VP16-induced gene expression in human cardiomyocytes
      grown under normoxic conditions. Luo et al. also show that a consensus E-box DNA
      binding sequence is necessary for appropriate BNP regulation. Because HIF-1 is
      known to elicit protective and beneficial gene expression programs in many
      scenarios and because BNP is known to be cardioprotective, this study provides
      support for the therapeutic use of the chimeric HIF-1alpha/VP16 protein in
      coronary heart disease. However, because HIF-1alpha is a key regulatory molecule
      that acts upon a large number of downstream gene networks, there remains a need
      for further investigation. Particularly useful would be comprehensive gene
      expression profiling coupled with functional analysis of HIF-1alpha/VP16
      regulated genes. The results of such studies will elucidate the mechanism of
      beneficial effects and address concerns regarding potential adverse effects of
      activating specific HIF-1alpha/VP16-dependent gene programs.

PMID- 16567546
TI  - Periodontal treatment and glycemic control in diabetic patients: the problem of a
      possible Hawthorne effect.

PMID- 16567547
TI  - "Know what" and "know how": knowledge creation in clinical practice.

PMID- 16567548
TI  - Dental flossing and interproximal caries: a systematic review.
AB  - Our aim was to assess, systematically, the effect of flossing on interproximal
      caries risk. Six trials involving 808 subjects, ages 4 to 13 years, were
      identified. There were significant study-to-study differences and a moderate to
      large potential for bias. Professional flossing performed on school days for 1.7
      years on predominantly primary teeth in children was associated with a 40% caries
      risk reduction (relative risk, 0.60; 95% confidence interval, 0.48-0.76; p-value,
      < 0.001). Both three-monthly professional flossing for 3 years (relative risk,
      0.93; 95% confidence interval, 0.73-1.19; p-value, 0.32) and self-performed
      flossing in young adolescents for 2 years (relative risk, 1.01; 95% confidence
      interval, 0.85-1.20; p-value, 0.93) did not reduce caries risk. No flossing
      trials in adults or under unsupervised conditions could be identified.
      Professional flossing in children with low fluoride exposures is highly effective
      in reducing interproximal caries risk. These findings should be extrapolated to
      more typical floss-users with care, since self-flossing has failed to show an
      effect.

PMID- 16567549
TI  - A critical review of non-carious cervical (wear) lesions and the role of
      abfraction, erosion, and abrasion.
AB  - The terms 'abfraction' and 'abrasion' describe the cause of lesions found along
      the cervical margins of teeth. Erosion, abrasion, and attrition have all been
      associated with their formation. Early research suggested that the cause of the V
      shaped lesion was excessive horizontal toothbrushing. Abfraction is another
      possible etiology and involves occlusal stress, producing cervical cracks that
      predispose the surface to erosion and abrasion. This article critically reviews
      the literature on abrasion, erosion, and abrasion, and abfraction. The references
      were obtained by a MEDLINE search in March, 2005, and from this, hand searches
      were undertaken. From the literature, there is little evidence, apart from
      laboratory studies, to indicate that abfraction exists other than as a
      hypothetical component of cervical wear.

PMID- 16567550
TI  - Cigarette smoking increases the risk of root canal treatment.
AB  - Few studies have investigated smoking as a risk factor for root canal treatment.
      We studied the effect of smoking on the incidence of root canal treatment,
      controlling for recognized risk factors, in 811 dentate male participants in the
      VA Dental Longitudinal Study. Participants were not VA patients. Follow-up ranged
      from 2 to 28 years. Root canal treatment was verified on radiographs and
      evaluated with proportional hazards regression models. Compared with never
      smokers, current cigarette smokers were 1.7 times as likely to have root canal
      treatment (p < 0.001), but cigar and/or pipe use was not significantly associated
      with root canal treatment. The risk among cigarette smokers increased with more
      years of exposure and decreased with length of abstinence. These findings suggest
      that there is a dose-response relationship between cigarette smoking and the risk
      of root canal treatment.

PMID- 16567551
TI  - Subgingival and tongue microbiota during early periodontitis.
AB  - Periodontal infections have a microbial etiology. Association of species with
      early disease would be useful in determining which microbes initiate
      periodontitis. We hypothesized that the microbiota of subgingival and tongue
      samples would differ between early periodontitis and health. A cross-sectional
      evaluation of 141 healthy and early periodontitis adults was performed with the
      use of oligonucleotide probes and PCR. Most species differed in associations with
      sample sites; most subgingival species were associated with subgingival samples.
      Few species were detected more frequently in early periodontitis by DNA probes.
      Porphyromonas gingivalis and Tannerella forsythia (Tannerella forsythensis) were
      associated with early periodontitis by direct PCR. In conclusion, the microbiota
      of tongue samples was less sensitive than that of subgingival samples in
      detecting periodontal species, and there was overlap in species detected in
      health and early periodontitis. Detection of periodontal pathogens in early
      periodontitis suggests an etiology similar to that of more advanced disease.

PMID- 16567552
TI  - Stress, cortisol, and periodontitis in a population aged 50 years and over.
AB  - Periodontitis and its relationship with psycho-neuro-immunological variables,
      such as psychological stress and cortisol, have been little explored. The
      objective of this study was to evaluate the extent and severity of chronic
      periodontitis and its association with the levels of salivary cortisol and the
      scores obtained with a stress questionnaire in a population aged 50 years and
      over. We studied 235 individuals in a cross-sectional study. They answered the
      Lipp's Inventory of Stress Symptoms for Adults, were instructed to collect three
      saliva samples for cortisol analysis, and were examined for evaluation for
      periodontitis. Based on logistic regression, cortisol levels were positively
      associated with the following outcomes: means of clinical attachment level (CAL)
      > = 4 mm [OR = 5.1, 95%CI (1.2, 20.7)]; 30% of sites with CAL > = 5 mm [OR = 6.9,
      95%CI (1.7, 27.1)]; and 26% of sites with probing depth > = 4 mm [OR = 10.7,
      95%CI (1.9, 54.1)] after adjustment for confounding variables. The results
      suggest that cortisol levels were positively associated with the extent and
      severity of periodontitis.

PMID- 16567553
TI  - Phenotypic variation in dentinogenesis imperfecta/dentin dysplasia linked to
      4q21.
AB  - Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders
      that primarily affect the formation of tooth dentin. Both conditions are
      autosomal-dominant and can be caused by mutations in the dentin
      sialophosphoprotein gene (DSPP, 4q21.3). We recruited 23 members of a four
      generation kindred, including ten persons with dentin defects, and tested the
      hypothesis that these defects are linked to DSPP. The primary dentition showed
      amber discoloration, pulp obliteration, and severe attrition. The secondary
      dentition showed either pulp obliteration with bulbous crowns and gray
      discoloration or thistle-tube pulp configurations, normal crowns, and mild gray
      discoloration. Haplotype analyses showed no recombination between three 4q21-q24
      markers and the disease locus. Mutational analyses identified no coding or intron
      junction sequence variations associated with affection status in DMP1, MEPE, or
      the DSP portion of DSPP. The defects in the permanent dentition were typically
      mild and consistent with a diagnosis of DD-II, but some dental features
      associated with DGI-II were also present. We conclude that DD-II and DGI-II are
      milder and more severe forms, respectively, of the same disease.

PMID- 16567554
TI  - Dental plaque pH and micro-organisms during hyposalivation.
AB  - We have previously reported that minor gland and whole saliva flow rates and
      salivary proteins showed differences in individuals with primary Sjogren's
      syndrome or head and neck radiation therapy, compared with controls (Eliasson et
      al., 2005). We now hypothesize that pH and number of acidogenic micro-organisms
      in dental plaque as well as saliva buffering capacity also differ in these
      individuals. Plaque pH was measured by the microtouch method up to 60 min after a
      sucrose rinse. Plaque collected from the same sites was analyzed for counts of
      total and acidic micro-organisms. Compared with their controls, the irradiated
      group but not the Sjogren's syndrome group displayed significantly lower plaque
      pH, increased numbers of lactobacilli and Candida species, as well as reduced
      buffering capacity. Stepwise regression tests suggested that the buccal minor
      salivary-gland secretion rate in the test groups and counts of mutans
      streptococci in the controls were of significant importance for dental plaque pH.

PMID- 16567556
TI  - Finger osteoarthritis and differences in dental work tasks.
AB  - Mechanical load has been proposed as a risk factor for hand osteoarthritis.
      Dentists produce high manual forces in their work tasks. We studied whether the
      pattern of dental work tasks was associated with finger osteoarthritis.
      Radiographs of both hands of 291 middle-aged female dentists were examined for
      the presence of osteoarthritis. Patterns of dental work tasks during work history
      were empirically defined by cluster analysis. Three patterns emerged reflecting
      high, moderate, and mild task variation. Age, specialization, years in clinical
      work, various activities requiring hand use, family history of Heberden's nodes,
      body mass index, and smoking were accounted for in logistic regression analyses.
      The dentists with a history of low task variation had a greater prevalence of
      osteoarthritis in the thumb, index, and middle fingers compared with dentists
      with high variation (OR 2.22; 95%CI 1.04-4.91). The pattern of dental work task
      history is associated with the localization of osteoarthritis in the fingers.

PMID- 16567555
TI  - Oral health beliefs in adolescence and oral health in young adulthood.
AB  - According to theory, health beliefs are related to health behaviors. We
      investigated whether individuals who hold favorable oral-health-related beliefs
      over time have better adult oral health than those who do not. Beliefs about the
      efficacy of water fluoridation, keeping the mouth clean, avoiding sweet foods,
      visiting the dentist, using dental floss, and using fluoridated toothpaste were
      assessed in a birth cohort at ages 15, 18, and 26 years. At each age, the
      majority of participants endorsed the importance of each practice. However, there
      was also evidence of instability across time. Individuals who held stable
      favorable dental beliefs from adolescence through adulthood had fewer teeth
      missing due to caries, less periodontal disease, better oral hygiene, better self
      rated oral health, and more restorations. Dental beliefs can change between
      adolescence and young adulthood, and these changes are related to oral health. In
      particular, unfavorable dental health beliefs are related to poorer oral health.

PMID- 16567557
TI  - Development of a self-etch adhesive for resin-modified glass ionomers.
AB  - The favorable self-adhesiveness of resin-modified glass ionomers (RMGIs) might be
      even further improved if the time-consuming and technically sensitive etch-and
      rinse pre-treatment step with polyalkenoic acids could be avoided. We undertook
      this study to assess the effectiveness of an experimental self-etch adhesive for
      RMGIs that does not need to be rinsed off. Ultrastructural analysis and micro
      tensile bond strength testing to enamel and dentin of a RMGI restorative material
      and a RMGI adhesive were performed after 4 different surface pre-treatments: no
      conditioning; 25% polyalkenoic acid; an experimental self-etch adhesive; and
      37.5% phosphoric acid followed by the experimental self-etch adhesive. The use of
      an experimental self-etch adhesive increased the bond strength of RMGIs,
      especially after an additional conditioning step. Interfacial analysis showed the
      formation of a thin hydroxyapatite-containing hybrid layer. The self-etch
      technique enhances the user-friendliness of RMGIs and lowers their technique
      sensitivity, while maintaining desirable characteristics of the conventional etch
      and-rinse approach with polyalkenoic acids.

PMID- 16567558
TI  - Effects of a hydroxyapatite-based biomaterial on gene expression in osteoblast
      like cells.
AB  - Biostite is a hydroxyapatite-derived biomaterial that is used in periodontal and
      bone reconstructive procedures due to its osteoconductive properties. Since the
      molecular effects of this biomaterial on osteoblasts are still unknown, we
      decided to assess whether it may specifically modulate osteoblast functions in
      vitro. We found that a brief exposure to Biostite significantly reduced the
      proliferation of MG-63 and SaOS-2 osteoblast-like cells to approximately 50% of
      the plateau value. Furthermore, gene array analysis of MG-63 cells showed that
      Biostite caused a differential expression of 37 genes which are involved in cell
      proliferation and interaction, and related to osteoblast differentiation and
      tissue regeneration. Results were confirmed by RT-PCR, Western blot, and by an
      increase in alkaline phosphatase (ALP) specific activity. Biostite also increased
      levels of polycystin-2, a mechano-sensitive Ca(2+) channel, a promising new
      marker of bone cell differentiation. Biostite, therefore, may directly affect
      osteoblasts by enhancing chondro/osteogenic gene expression and cytoskeleton
      related signaling pathways, which may contribute to its clinical efficacy.

PMID- 16567560
TI  - Impact of endodontic treatments on the rigidity of the root.
AB  - The destabilizing effect of endodontic treatment upon teeth is still
      controversial. The purpose of this study was to investigate the effects of
      different steps of endodontic treatments upon the rigidity of teeth. Extracted
      untreated central maxillary anterior teeth were loaded (3.75 N), and deformations
      of the root were assessed by Speckle pattern interferometry. The following
      treatments (with subsequent determination of deformability) were conducted
      sequentially: access preparation, manual instrumentation (Kerr files ISO-40, ISO
      60, ISO-80, ISO-110), and tapered and parallel-sided post preparation. It was
      found that the teeth were increasingly destabilized by any treatment. While the
      increased deformability was not significant with the manual enlargement (p >
      0.05), we found a significant destabilization after access preparation and post
      preparation (p < 0.05). A corresponding difference was found after conversion of
      the post preparation from tapered to parallel-sided (p < 0.05). Both substance
      loss and modifications of the natural root canal geometry play an important role
      in tooth rigidity.

PMID- 16567559
TI  - Enamel demineralization in primary and permanent teeth.
AB  - Although enamel demineralization is important for our understanding of caries
      formation, no consensus has been reached regarding the possible differences in
      susceptibility of primary and permanent enamel. We used the constant composition
      (CC) technique to investigate the acid-induced demineralization of these tissues
      at a relative undersaturation with respect to hydroxyapatite (HAP) of 0.902, pH =
      4.5, and ionic strength = 0.15 mol L(-1). The demineralization rates showed
      significant differences, primary enamel having the greater susceptibility to
      dissolution during an initial linear stage: 1.5 +/- 0.5 x 10(-10) mol mm(-2) min(
      1) compared with 2.6 +/- 0.5 x 10(-11) mol mm(-2) min(-1) for permanent enamel.
      During the reactions, we observed nanosized crystallites which attached to the
      enamel surfaces or escaped into the bulk solution. These nanosized crystallites
      were kinetically protected against further dissolution, even though the solutions
      remained undersaturated. It is hypothesized that they may contribute to the
      remarkable mechanical and dynamic characteristics of enamel.

PMID- 16567561
TI  - Streptococcus mutans: fructose transport, xylitol resistance, and virulence.
AB  - Streptococcus mutans, the primary etiological agent of human dental caries,
      possesses at least two fructose phosphotransferase systems (PTSs), encoded by
      fruI and fruCD. fruI is also responsible for xylitol transport. We hypothesized
      that fructose and xylitol transport systems do not affect virulence. Thus,
      colonization and cariogenicity of fruI(-) and fruCD(-) single and double mutants,
      their WT (UA159), and xylitol resistance (X(r)) of S. mutans were studied in rats
      fed a high-sucrose diet. A sucrose phosphorylase (gtfA(-)) mutant and a reference
      strain (NCTC-10449S) were additional controls. Recoveries of fruI mutant from the
      teeth were decreased, unlike those for the other strains. The fruCD mutation was
      associated with a slight loss of cariogenicity on enamel, whereas mutation of
      fruI was associated with a loss of cariogenicity in dentin. These results also
      suggest why xylitol inhibition of caries is paradoxically associated with
      spontaneous emergence of so-called X(r) S. mutans in habitual human xylitol
      users.

PMID- 16567562
TI  - Role of secreted frizzled-related protein 1 (SFRP1) in wound healing.
AB  - Wound healing is a complex cascade of events, which diminishes the size of the
      wound and reestablishes tissue integrity. Secreted frizzled-related protein 1
      (SFRP1) contributes to the inhibition of apoptosis in fibroblast populations. We
      investigated the role of SFRP1 in a mouse wound-healing model; 2.0-mm excisional
      wounds were created in the scalp and hard palate. Healing responses were measured
      by histomorphometric analysis, apoptosis assay, and immunohistochemistry. Dermal
      wounds did not harbor SFRP1, but healed faster than palatal wounds which
      expressed significant levels of SFRP1. Antibody experiments aimed at blocking
      SFRP1 in palatal wounds resulted in promotion of wound closure, enhancement of
      new tissue formation, decrease of inflammatory cell infiltrate, and increase of
      apoptotic fibroblasts. Analysis of the present data suggests that SFRP1 may be
      partly responsible for the poorer healing performance of the palatal wounds
      compared with dermal wounds. Blocking SFRP1 results in improvement of palatal
      healing outcomes.

PMID- 16567563
TI  - Effects of isoflurane on parasympathetic vasodilatation in the rat submandibular
      gland.
AB  - Volatile anesthetics have been known to suppress parasympathetic reflex
      vasodilatation in the lower lip and palate. However, in the submandibular gland,
      little is known about the effects of these anesthetics on the parasympathetic
      vasodilatation elicited by reflex and direct (i.e., non-reflex) activation of the
      parasympathetic vasodilator mechanisms. Although both parasympathetic
      vasodilatations were inhibited by isoflurane in a concentration- and time
      dependent manner, the effects of continuous administration of the alpha(1)
      adrenoceptor agonist methoxamine were markedly different: The reflex
      vasodilatation was not affected by methoxamine, while the direct vasodilatation
      was significantly reduced. Picrotoxin (GABA(A) receptor antagonist) attenuated
      the inhibitory effect of isoflurane on direct vasodilatation and the systemic
      arterial blood pressure. These findings suggest that the isoflurane-induced
      inhibitory effects on direct vasodilatation are produced by a decrease of
      peripheral vascular tone by GABAergic mechanisms, whereas those on the reflex
      vasodilatation are produced exclusively by the inhibition of the reflex center.

PMID- 16567564
TI  - Clinical stress testing in the pediatric age group: a statement from the American
      Heart Association Council on Cardiovascular Disease in the Young, Committee on
      Atherosclerosis, Hypertension, and Obesity in Youth.
AB  - This statement is an updated report of the American Heart Association's previous
      publications on exercise in children. In this statement, exercise laboratory
      requirements for environment, equipment, staffing, and procedures are presented.
      Indications and contraindications to stress testing are discussed, as are types
      of testing protocols and the use of pharmacological stress protocols. Current
      stress laboratory practices are reviewed on the basis of a survey of pediatric
      cardiology training programs.

PMID- 16567565
TI  - Contemporary definitions and classification of the cardiomyopathies: an American
      Heart Association Scientific Statement from the Council on Clinical Cardiology,
      Heart Failure and Transplantation Committee; Quality of Care and Outcomes
      Research and Functional Genomics and Translational Biology Interdisciplinary
      Working Groups; and Council on Epidemiology and Prevention.
AB  - Classifications of heart muscle diseases have proved to be exceedingly complex
      and in many respects contradictory. Indeed, the precise language used to describe
      these diseases is profoundly important. A new contemporary and rigorous
      classification of cardiomyopathies (with definitions) is proposed here. This
      reference document affords an important framework and measure of clarity to this
      heterogeneous group of diseases. Of particular note, the present classification
      scheme recognizes the rapid evolution of molecular genetics in cardiology, as
      well as the introduction of several recently described diseases, and is unique in
      that it incorporates ion channelopathies as a primary cardiomyopathy.

PMID- 16567566
TI  - Idiopathic epicardial left ventricular tachycardia originating remote from the
      sinus of Valsalva: electrophysiological characteristics, catheter ablation, and
      identification from the 12-lead electrocardiogram.
AB  - BACKGROUND: Despite the success of catheter ablation for treatment of idiopathic
      ventricular tachycardia (VT), occasional patients have been reported in whom VT
      could not be ablated from the right or left ventricular endocardium or from the
      aortic sinus of Valsalva (ASOV). METHODS AND RESULTS: In 12 of 138 patients (9%)
      with idiopathic VT referred for ablation, an epicardial left ventricular site of
      origin was identified >10 mm from the ASOV. Coronary venous mapping demonstrated
      epicardial preceding endocardial activation by >10 ms (41+/-7 versus 15+/-11 ms
      before QRS onset; P<0.001). VT induction was facilitated by catecholamines and
      terminated by adenosine. Ablation through the coronary veins or via percutaneous
      transpericardial catheterization was successful in 9 patients; 2 required direct
      surgical ablation as a result of anatomic constraints. No ECG pattern was
      specific for epicardial VT. However, slowed initial precordial QRS activation, as
      quantified by a novel metric, the maximum deflection index, was more useful. A
      delayed precordial maximum deflection index > or =0.55 identified epicardial VT
      remote from the ASOV with a sensitivity of 100% and a specificity of 98.7%
      relative to all other sites of origin (P<0.001). CONCLUSIONS: Although clinically
      underrecognized, idiopathic VT may originate from the perivascular sites on the
      left ventricular epicardium. The mechanism is consistent with triggered activity.
      It is amenable to ablation by transvenous or transpericardial approaches,
      although technical challenges remain. Recognition of a prolonged precordial
      maximum deflection index and early use of transvenous epicardial mapping are
      critical to avoid protracted and unsuccessful ablation elsewhere in the
      ventricles.

PMID- 16567567
TI  - Plakophilin-2 mutations are the major determinant of familial arrhythmogenic
      right ventricular dysplasia/cardiomyopathy.
AB  - BACKGROUND: Mutations in the plakophilin-2 gene (PKP2) have been found in
      patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC).
      Hence, genetic screening can potentially be a valuable tool in the diagnostic
      workup of patients with ARVC. METHODS AND RESULTS: To establish the prevalence
      and character of PKP2 mutations and to study potential differences in the
      associated phenotype, we evaluated 96 index patients, including 56 who fulfilled
      the published task force criteria. In addition, 114 family members from 34 of
      these 56 ARVC index patients were phenotyped. In 24 of these 56 ARVC patients
      (43%), 14 different (11 novel) PKP2 mutations were identified. Four different
      mutations were found more than once; haplotype analyses revealed identical
      haplotypes in the different mutation carriers, suggesting founder mutations. No
      specific genotype-phenotype correlations could be identified, except that
      negative T waves in V(2) and V(3) occurred more often in PKP2 mutation carriers
      (P<0.05). Of the 34 index patients whose family members were phenotyped, 23
      familial cases were identified. PKP2 mutations were identified in 16 of these 23
      ARVC index patients (70%) with familial ARVC. On the other hand, no PKP2
      mutations at all were found in 11 probands without additional affected family
      members (P<0.001). CONCLUSIONS: PKP2 mutations can be identified in nearly half
      of the Dutch patients fulfilling the ARVC criteria. In familial ARVC, even the
      vast majority (70%) is caused by PKP2 mutations. However, nonfamilial ARVC is not
      related to PKP2. The high yield of mutational analysis in familial ARVC is unique
      in inherited cardiomyopathies.

PMID- 16567568
TI  - Association between human fetuin-A and the metabolic syndrome: data from the
      Heart and Soul Study.
AB  - BACKGROUND: Fetuin-A is a multifunctional hepatic secretory protein that inhibits
      the action of insulin in experimental animals. We evaluated the association
      between human serum fetuin-A and the metabolic syndrome (MetS) in a cohort of
      persons with coronary artery disease. METHODS AND RESULTS: We defined MetS by the
      National Cholesterol Education Program criteria among 711 nondiabetic outpatients
      with coronary artery disease. The mean age was 67 years, and 82% were male. We
      divided participants into quartiles by serum fetuin-A concentrations. A total of
      45% of participants (80 of 177) in the highest quartile of fetuin-A had MetS
      compared with 24% of participants (42 of 177) in the lowest quartile (odds ratio,
      2.7; 95% confidence interval, 1.7 to 4.2; P<0.001). This association persisted
      after adjustment for potential confounding variables, including hypertension,
      body mass index, and inflammatory biomarkers (adjusted odds ratio, 2.0; 95%
      confidence interval, 1.1 to 3.5; P=0.02). Higher fetuin-A quartiles were also
      strongly and independently associated with higher low-density lipoprotein, non
      high-density lipoprotein (HDL), and triglyceride concentrations and lower HDL
      concentrations (all P<0.01). CONCLUSIONS: Higher human fetuin-A concentrations
      are strongly associated with MetS and an atherogenic lipid profile. Future
      studies should evaluate whether fetuin-A predicts coronary artery disease risk.

PMID- 16567569
TI  - Magnesium intake and incidence of metabolic syndrome among young adults.
AB  - BACKGROUND: Studies suggest that magnesium intake may be inversely related to
      risk of hypertension and type 2 diabetes mellitus and that higher intake of
      magnesium may decrease blood triglycerides and increase high-density lipoprotein
      (HDL) cholesterol levels. However, the longitudinal association of magnesium
      intake and incidence of metabolic syndrome has not been investigated. METHODS AND
      RESULTS: We prospectively examined the relations between magnesium intake and
      incident metabolic syndrome and its components among 4637 Americans, aged 18 to
      30 years, who were free from metabolic syndrome and diabetes at baseline.
      Metabolic syndrome was diagnosed according to the National Cholesterol Education
      Program/Adult Treatment Panel III definition. Diet was assessed by an interviewer
      administered quantitative food frequency questionnaire, and magnesium intake was
      derived from the nutrient database developed by the Minnesota Nutrition
      Coordinating Center. During the 15 years of follow-up, 608 incident cases of the
      metabolic syndrome were identified. Magnesium intake was inversely associated
      with incidence of metabolic syndrome after adjustment for major lifestyle and
      dietary variables and baseline status of each component of the metabolic
      syndrome. Compared with those in the lowest quartile of magnesium intake,
      multivariable-adjusted hazard ratio of metabolic syndrome for participants in the
      highest quartile was 0.69 (95% confidence interval [CI], 0.52 to 0.91; P for
      trend <0.01). The inverse associations were not materially modified by gender and
      race. Magnesium intake was also inversely related to individual component of the
      metabolic syndrome and fasting insulin levels. CONCLUSIONS: Our findings suggest
      that young adults with higher magnesium intake have lower risk of development of
      metabolic syndrome.

PMID- 16567570
TI  - Effect of clopidogrel premedication in off-pump cardiac surgery: are we
      forfeiting the benefits of reduced hemorrhagic sequelae?
AB  - BACKGROUND: Premedication with clopidogrel has reduced thrombotic complications
      after percutaneous coronary revascularization procedures. However, because of the
      enhanced and irreversible platelet inhibition by clopidogrel, patients requiring
      surgical revascularization have a higher risk of bleeding complications and
      transfusion requirements. A principal benefit of surgical coronary
      revascularization without cardiopulmonary bypass is its lower hemorrhagic
      sequelae. The purpose of this study was to evaluate the effect of preoperative
      clopidogrel administration in the incidence of hemostatic reexploration, blood
      product transfusion rates, morbidity, and mortality in patients undergoing off
      pump coronary artery bypass graft surgery using a large patient sample and a risk
      adjusted approach. METHODS AND RESULTS: Two hundred eighty-one patients (17.9%)
      did and 1291 (82.1%) did not receive clopidogrel before their surgery, for a
      total of 1572 patients undergoing isolated off-pump coronary artery bypass graft
      surgery between January 2000 and June 2002. Risk-adjusted logistic regression
      analyses and a matched pair analyses by propensity scores were used to assess the
      association between clopidogrel administration and reoperation as a result of
      bleeding, intraoperative and postoperative blood transfusions received, and the
      need for multiple transfusions. Hemorrhage-related preoperative risk factors
      identified in the literature and those found significant in a univariate model
      were used. The clopidogrel group had a higher likelihood of hemostatic
      reoperations (odds ratio [OR], 5.1; 95% confidence interval [CI], 2.47 to 10.47;
      P<0.01) and an increased need in overall packed red blood cell (OR, 2.6; 95% CI,
      1.94 to 3.60; P<0.01), multiple unit (OR, 1.6; 95% CI, 1.07 to 2.48; P=0.02), and
      platelet (OR, 2.5; 95% CI, 1.77 to 3.66; P<0.01) transfusions. Surgical outcomes
      and operative mortality (1.4% versus 1.4%; P=1.00) were not statistically
      different. CONCLUSIONS: Clopidogrel administration in the cardiology suite
      increases the risk for hemostatic reoperation and the requirements for blood
      product transfusions during and after off-pump coronary artery bypass graft
      surgery.

PMID- 16567571
TI  - Abdominal aortic aneurysm is associated with high serum levels of tenascin-X and
      decreased aneurysmal tissue tenascin-X.
AB  - BACKGROUND: Tenascin-X is a large extracellular matrix protein that is abundantly
      expressed in several connective tissues. A 140-kDa C-terminal fragment of
      tenascin-X is present in human serum. Complete deficiency of tenascin-X is
      associated with Ehlers-Danlos syndrome, and these patients show major connective
      tissue alterations in their skin, as well as blood vessel fragility. In this
      study, we investigated whether tenascin-X is present in normal human aorta and
      abdominal aortic aneurysm (AAA) tissues and whether an association exists between
      serum tenascin-X levels and AAA. METHODS AND RESULTS: Five normal aortas and 5
      AAA tissues were immunostained for tenascin-X and elastin. Tenascin-X was present
      throughout the entire aorta and was especially abundant near the elastic
      lamellae, whereas tenascin-X expression was strongly decreased in AAA tissue.
      Measurement of tenascin-X serum concentration by enzyme-linked immunosorbent
      assay (ELISA) in 87 AAA patients and 86 controls demonstrated an increasing risk
      for AAA with increasing tenascin-X serum concentrations. After adjustment for
      established risk factors, tenascin-X serum concentrations in the highest quartile
      were associated with a 5-fold increase in risk of AAA (odds ratio, 5.3; 95%
      confidence interval, 2.0 to 13.8). CONCLUSIONS: Tenascin-X expression is markedly
      decreased in AAA tissue, and AAA is associated with high serum concentrations of
      tenascin-X.

PMID- 16567572
TI  - Gastrointestinal complications of dual antiplatelet therapy.

PMID- 16567573
TI  - Images in cardiovascular medicine. Severe left atrial edema and heart failure
      after atrial fibrillation ablation.

PMID- 16567574
TI  - Images in cardiovascular medicine. Serial high-spatial-resolution, multisequence
      magnetic resonance imaging studies identify fibrous cap rupture and penetrating
      ulcer into carotid atherosclerotic plaque.

PMID- 16567575
TI  - Images in cardiovascular medicine. Diffuse infiltration of lymphoma of the
      myocardium mimicking clinical hypertrophic cardiomyopathy.

PMID- 16567576
TI  - Letter regarding article by Staat et al, "postconditioning the human heart".

PMID- 16567577
TI  - A view from Sofia.

PMID- 16567578
TI  - Vitamin K epoxide reductase complex and vascular calcification: is this the
      important link between vitamin K and the arterial vessel wall?

PMID- 16567579
TI  - Cardioprotective properties of fibrates: which fibrate, which patients, what
      mechanism?

PMID- 16567580
TI  - Women have higher left ventricular ejection fractions than men independent of
      differences in left ventricular volume: the Dallas Heart Study.
AB  - BACKGROUND: Although gender-specific criteria are common for defining cardiac
      traits such as left ventricular hypertrophy, left ventricular ejection fraction
      (LVEF) thresholds widely used in clinical practice have traditionally been the
      same for women and men, perhaps because it remains uncertain whether there is a
      systematic difference in LVEF between genders. METHODS AND RESULTS: Using cardiac
      magnetic resonance imaging in a probability-based sample of Dallas County
      residents aged 30 to 65 years (1435 women and 1183 men), we compared LVEF in
      women and men. The association of gender with stroke volume independent of end
      diastolic volume (EDV) or other potential confounders was assessed by
      multivariable analysis. Gender-specific thresholds for a low LVEF were defined at
      the 2.5th percentile in women and men from a healthy reference subpopulation. The
      median (25th, 75th percentile) LVEF was higher in women than in men (75% [70%,
      79%] in women versus 70% [65%, 75%] in men, P<0.001). Left ventricular EDV and
      end-systolic volume indexed to body surface area were smaller in women than in
      men (P<0.001 for both). Gender remained significantly associated with stroke
      volume, independent of EDV and other potential confounders in multivariable
      analysis. A low LVEF was defined as below 61% in women and below 55% in men.
      CONCLUSIONS: Women have a higher LVEF than men in the general population,
      secondary to a higher stroke volume for a given EDV independent of known
      potential confounders.

PMID- 16567581
TI  - Pericardial disease.

PMID- 16567583
TI  - Leptin, endothelin, NADPH oxidase, and heart failure.

PMID- 16567584
TI  - Emergence of novel genetic effects on blood pressure and hemodynamics in
      adolescence: the Georgia Cardiovascular Twin Study.
AB  - Multiple longitudinal studies have demonstrated reasonable stability of blood
      pressure (BP) levels and hemodynamics throughout childhood and adolescence and
      into adulthood. Part of this stability might be caused by genetic factors that
      are expressed steadily over time. We aimed to determine the relative
      contributions of genetic and environmental factors to the stability of BP and
      underlying hemodynamic characteristics between ages 14 and 18 years. In addition,
      potential ethnic differences were examined. To this end, resting levels of BP and
      impedance-derived hemodynamic variables were measured twice in >500 pairs of
      European American (EA) and African American (AA) twins, with an intervening
      period of 4.1 years. Structural equation modeling of the twin data on BP and
      underlying hemodynamic variables (adjusted for age, sex, and body mass index)
      showed that heritabilities were moderate to high (25% to 64%) and relatively
      stable over time. These genetic influences accounted for 60% to 100% of the
      phenotypic tracking correlations (range 0.39 to 0.62). Emergence of novel genetic
      influences accounted for a significant part of the variance (17% to 33%) at the
      second measurement occasion. There were significant ethnic differences for BP,
      with nonshared environmental influences becoming larger over time in AAs compared
      with EAs for both systolic and diastolic BP. In summary, novel genetic effects
      emerge during development into adulthood and explain a considerable part of the
      variation in BP and hemodynamics. Environmental influences become more important
      with age in AAs compared with EAs for both systolic and diastolic BP. Future
      elucidation of these environmental factors may help explain ethnic differences in
      hypertension risk.

PMID- 16567585
TI  - Polymorphism in endothelin-related genes limits exercise-induced decreases in
      arterial stiffness in older subjects.
AB  - Increase in arterial stiffness is associated with aging, which is improved by
      regular exercise. Endothelin (ET) system has crucial roles in regulating vascular
      tone and in the progression of atherosclerosis. We hypothesized that molecular
      variations (ie, gene polymorphisms) in ET-related gene might affect exercise
      induced improvement in arterial stiffness with age in human subjects. The present
      study provides a cross-sectional investigation of 191 healthy middle-aged and
      older (65+/-1 years) human subjects to clarify the relationship between the
      regular exercise-induced improvement of arterial stiffness and the gene
      polymorphisms of ET converting enzyme (ECE)-1, ECE-2, ET-A receptor (ET-A), and
      ET-B receptor (ET-B). The study subjects were divided into active and inactive
      groups based on the median value (186 kcal/d) of energy expenditure. Brachial
      ankle arterial pulse wave velocity (baPWV) was used to evaluate arterial
      stiffness. All individuals were genotyped for 4 different polymorphisms of the ET
      system: 2013(+289)A/G in intron 17 of ECE-1, 669(+17)T/C in intron 5 of ECE-2,
      958A/G in exon 6 of ET-A, and 831A/G in exon 4 of ET-B. The baseline baPWV was
      significantly lower in the active group without any change in blood pressure.
      Polymorphisms in ECE-1 influenced basal blood pressure. Polymorphisms in ECE-1
      and ECE-2 had no effect on baPWV between active and inactive groups. However,
      polymorphisms in both ET-A and ET-B affected baPWV in the 2 groups. The present
      results suggest that differences in ET-A and ET-B polymorphisms may influence the
      response of the vascular wall to exercise whereas ECE-1 polymorphisms may affect
      basal blood pressure.

PMID- 16567586
TI  - Association of hemoglobin delivery with left ventricular structure and function
      in hypertensive patients: Losartan Intervention for End Point Reduction in
      Hypertension Study.
AB  - Several studies have shown associations of high levels of hemoglobin (Hgb) or
      blood viscosity with cardiac events and with left ventricular (LV) hypertrophy
      (LVH). To assess the relations of LV mass and function with Hgb delivery (ie, the
      physiological carrier of oxygen), we calculated the product of Hgb concentration
      and Doppler-derived cardiac output in 864 hypertensive participants with
      electrocardiographic LVH (359 women) in the Losartan Intervention for End Point
      Reduction in Hypertension echocardiography substudy. Among women, Hgb delivery
      was positively related to internal dimension, septal and posterior wall
      thicknesses, LV mass, endocardial and midwall fractional shortening, and peak A
      wave velocity and negatively to total peripheral resistance index, E/A ratio,
      deceleration time, and the isovolumic relaxation time. Among men, Hgb delivery
      was positively related to LV internal dimension, LV mass, and A velocity, and
      negatively to LV midwall shortening, relative wall thickness, peripheral
      resistance index, and E/A ratio. In multivariable analyses that adjusted for age,
      diastolic blood pressure, body mass index, and total cholesterol, hemoglobin
      delivery in women was related positively to LV fractional shortening, midwall
      shortening, LV mass mitral valve A velocity, and LV internal dimension and
      negatively to mitral valve deceleration time and isovolumic relaxation time.
      Among men, Hgb delivery had positive independent relations to mitral valve A
      velocity, LV internal dimension, midwall shortening, and LV mass and negative
      relations to the E/A ratio and relative wall thickness. Thus, in hypertensive
      LVH, higher oxygen delivery capacity is associated with higher LV mass and
      impaired early diastolic LV filling.

PMID- 16567587
TI  - Compared with whom? Addressing the prognostic value of ambulatory blood pressure
      categories.

PMID- 16567588
TI  - Long-term risk of mortality associated with selective and combined elevation in
      office, home, and ambulatory blood pressure.
AB  - In the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study, office,
      home, and ambulatory blood pressure (BP) values were measured contemporaneously
      between 1990 and 1993 in a large population sample (n=2051). Cardiovascular (CV)
      and non-CV death certificates were collected over the next 148 months, which
      allowed us to assess the prognostic value of selective and combined elevation in
      these 3 BPs over a long follow-up. There were 69 CV and 233 all-cause deaths.
      Compared with subjects with normal office and 24-hour BP, the hazard ratio for CV
      death showed a progressive increase in those with a selective office BP elevation
      (white-coat hypertension), a selective 24-hour BP elevation (masked
      hypertension), and elevation in both office and 24-hour BP. This was the case
      also when the above conditions were identified by office versus home BP values.
      Selective elevation in home versus ambulatory BP or vice versa also carried an
      increased risk. There was indeed a progressive increase in both CV and all-cause
      mortality risk from subjects in whom office, home, and ambulatory BP were all
      normal to those in whom 1, 2, or all 3 BPs were elevated, regardless of which BP
      was considered. The trends remained significant after adjustment for age and
      gender, as well as, in most instances, after further adjustment for other
      cardiovascular risk factors. Thus, white-coat hypertension and masked
      hypertension, both when identified by office and ambulatory or by office and home
      BPs, are not prognostically innocent. Indeed, each BP elevation (office, home, or
      ambulatory) carries an increase in risk mortality that adds to that of the other
      BP elevations.

PMID- 16567589
TI  - Impairment of in vitro and in vivo heart function in angiotensin-(1-7) receptor
      MAS knockout mice.
AB  - In this study we investigated the effects of the genetic deletion of the
      angiotensin (Ang)-(1-7) receptor Mas on heart function. Localization of Mas in
      the mouse heart was evaluated by binding of rhodamine-labeled Ang-(1-7). Cardiac
      function was examined using isolated heart preparations. Echocardiography was
      used to confirm the results obtained with isolated heart studies. To elucidate
      the possible mechanisms involved in the cardiac phenotype observed in Mas(-/-)
      mice, whole-cell calcium currents in cardiomyocytes and the expression of
      collagen types I, III, and VI and fibronectin were analyzed. Ang-(1-7) binding
      showed that Mas is localized in cardiomyocytes of the mouse heart. Isolated heart
      techniques revealed that Mas-deficient mice present a lower systolic tension
      (average: 1.4+/-0.09 versus 2.1+/-0.03 g in Mas(+/+) mice), +/-dT/dt, and heart
      rate. A significantly higher coronary vessel resistance was also observed in Mas
      deficient mice. Echocardiography revealed that hearts of Mas-deficient mice
      showed a significantly decreased fractional shortening, posterior wall thickness
      in systole and left ventricle end-diastolic dimension, and a higher left
      ventricle end-systolic dimension. A markedly lower global ventricular function,
      as defined by a higher myocardial performance index, was observed. A higher
      delayed time to the peak of calcium current was also observed. The changes in
      cardiac function could be partially explained by a marked change in collagen
      expression to a profibrotic profile in Mas-deficient mice. These results indicate
      that Ang-(1-7)-Mas axis plays a key role in the maintenance of the structure and
      function of the heart.

PMID- 16567590
TI  - Microvascular plasticity and experimental heart failure.

PMID- 16567591
TI  - Vascular endothelial growth factor blockade promotes the transition from
      compensatory cardiac hypertrophy to failure in response to pressure overload.
AB  - Cardiac hypertrophy is associated with upregulation of vascular endothelial
      growth factor (VEGF) in the myocardium. Here, we evaluated the effects of a decoy
      VEGF receptor on heart morphology and function to a murine model of pressure
      overload hypertrophy. Mice were administered adenoviral vector encoding a decoy
      VEGF receptor (Ad-Flk), and their hearts were subjected to pressure overload by
      transverse aortic constriction (TAC). Treatment with Ad-Flk led to a net
      reduction in capillary density in hearts subjected to TAC. Ad-Flk also led to a
      reduction in TAC-induced cardiac hypertrophy and promoted left ventricle
      dilatation and a loss in contractile function. Treatment with Ad-Flk markedly
      increased myocardial fibrosis and collagen gene upregulation. In contrast, Ad-Flk
      had no effect on any of these parameters in sham-treated mice. Administration of
      a VEGF trap reagent diminished pressure overload cardiac hypertrophy and promoted
      the progression to heart failure but had no effect on sham-treated animals. These
      findings suggest that VEGF is required to maintain myocardial capillary density
      and that reductions in the vascular bed are associated with the transition from
      compensatory hypertrophy to failure.

PMID- 16567592
TI  - Telmisartan: the ACE of ARBs?

PMID- 16567593
TI  - Telmisartan but not valsartan increases caloric expenditure and protects against
      weight gain and hepatic steatosis.
AB  - The potential effects of angiotensin II receptor blockers (ARBs) on adipose
      tissue biology and body weight are of considerable interest, because these agents
      are frequently used to treat hypertension in patients who are prone to visceral
      obesity, the metabolic syndrome, and diabetes. In rats fed a high-fat, high
      carbohydrate diet, we compared the effects of 2 ARBs, telmisartan and valsartan,
      on body weight, food intake, energy expenditure, fat accumulation, fat cell size,
      and hepatic triglyceride levels. Telmisartan, but not valsartan, promoted
      increases in caloric expenditure and protected against dietary-induced weight
      gain. In the telmisartan-treated rats, absolute food intake, but not food intake
      adjusted for body weight, was lower than in valsartan-treated rats or controls.
      Telmisartan reduced the accumulation of visceral fat and decreased adipocyte size
      to a much greater extent than valsartan and was also associated with a
      significant reduction in hepatic triglyceride levels. Moreover, telmisartan, but
      not valsartan, increased the expression of both nuclear-encoded and mitochondrial
      encoded genes in skeletal muscle known to play important roles in mitochondrial
      energy metabolism. Thus, in addition to a class effect of ARBs in modulating
      adipocyte size, these findings raise the possibility that certain molecules, like
      telmisartan, may have a particularly strong impact on fat cell volume and fat
      accumulation, as well as distinctive effects on energy metabolism, that may help
      protect against dietary-induced visceral obesity and weight gain.

PMID- 16567594
TI  - Association of the Ghrelin receptor gene region with left ventricular hypertrophy
      in the general population: results of the MONICA/KORA Augsburg Echocardiographic
      Substudy.
AB  - Growth hormone (GH) can influence left ventricular myocardial growth, structure,
      and function. The GH secretagogue receptor (GHSR, ghrelin receptor) is known to
      be involved in GH release and is expressed in the myocardium. We hypothesized
      that genetic variants within the GHSR are associated with parameters of left
      ventricular mass (LVM) and geometry. Ten single-nucleotide polymorphisms (SNPs)
      covering the gene region were genotyped in 1230 members of the general population
      (Monitoring Trends and Determinants on Cardiovascular Diseases Augsburg
      Echocardiographic Substudy). Linkage disequilibrium analysis revealed a linkage
      disequilibrium block consisting of 5 SNPs forming 2 common haplotypes. One
      haplotype was found significantly more often in subjects without left ventricular
      hypertrophy ([LVH] 69% versus 59%; permutated P=0.0015), whereas the second
      haplotype was significantly more frequent in individuals with LVH (32% versus
      26%; P=0.019). Homozygous subjects presented with an increase of risk with
      respect to all heart size parameters. A significantly increasing frequency of the
      risk haplotype could be observed from the lowest (20.9%) to the highest quintile
      (31.0%) of gender-specific LVM distributions (P=0.0096). We found association of
      the minor alleles of individual single nucleotide polymorphisms contributing to
      the haplotypes with higher LVM indices, septal wall thickness, and different LVH
      criteria consistent in men and women in matched cases and controls (LVM, women:
      144.8+/-30.9 [noncarrier] versus 171.3+/-36.0 [homozygous], P=0.001; men: 186.7+/
      42.4 versus 236.3+/-64.5, P=0.002). These data suggest that common variants in
      the GHSR region are associated with parameters of LVM and geometry independent of
      blood pressure and body mass in the general population and, thus, may be involved
      in the pathogenesis of LVH.

PMID- 16567595
TI  - Increased sympathetic nerve activity correlates with neurovascular compression at
      the rostral ventrolateral medulla.
AB  - We used microneurography to measure muscle sympathetic nerve activity (MSNA) in
      25 hypertensive subjects and correlated these results with the presence or
      absence of signs of neurovascular compression (NVC) at the rostral ventrolateral
      (RVL) medulla on MRI. Subjects were divided into 3 groups based on MRI findings:
      NVC-, no MRI evidence of NVC (N=9); NVC+contact, image showing artery in contact
      but not compressing the RVL medulla (N=8); and NVC+compression, image showing
      arterial compression of the RVL medulla (N=8). The MSNA measurements were
      performed at rest, after a hypothermic stimulus, and during isometric exercise.
      The MSNA during rest in the NVC+compression group was significantly higher than
      that in the NVC+contact and NVC- groups (30.4+/-3.4 versus 17.5+/-1.1 and 21.4+/
      3.2 spikes per minute, respectively). However, the blood pressure in the
      NVC+compression group was slightly but not significantly higher than that in the
      other 2 groups (183+/-7/115+/-8, 174+/-6/108+/-7, and 171+/-5/110+/-5 mm Hg,
      respectively). The increases in MSNA, blood pressure, and heart rate during the
      cold pressor and isometric exercise tests were similar. Our results show that,
      although resting MSNA is elevated in patients with true NVC of the RVL medulla,
      patients without NVC or with arterial contact but not overt compression of the
      RVL medulla have similar MSNA. These findings are important for identifying,
      among hypertensive patients with NVC, individuals who may have associated
      physiological repercussions, such as increased sympathetic activity.

PMID- 16567596
TI  - Time, now, to recover the fun in the physical examination rather than abandon it.

PMID- 16567597
TI  - Reconsidering medication appropriateness for patients late in life.

PMID- 16567598
TI  - Competency in cardiac examination skills in medical students, trainees,
      physicians, and faculty: a multicenter study.
AB  - BACKGROUND: Cardiac examination is an essential aspect of the physical
      examination. Previous studies have shown poor diagnostic accuracy, but most used
      audio recordings, precluding correlation with visible observations. The training
      spectrum from medical students (MSs) to faculty has not been tested, to our
      knowledge. METHODS: A validated 50-question, computer-based test was used to
      assess 4 aspects of cardiac examination competency: (1) cardiac physiology
      knowledge, (2) auditory skills, (3) visual skills, and (4) integration of
      auditory and visual skills using computer graphic animations and virtual patient
      examinations (actual patients filmed at the bedside). We tested 860 participants:
      318 MSs, 289 residents (225 internal medicine and 64 family medicine), 85
      cardiology fellows, 131 physicians (50 full-time faculty, 12 volunteer clinical
      faculty, and 69 private practitioners), and 37 others. RESULTS: Mean scores
      improved from MS1-2 to MS3-4 (P = .003) but did not improve or differ
      significantly among MS3, MS4, internal medicine residents, family medicine
      residents, full-time faculty, volunteer clinical faculty, and private
      practitioners. Only cardiology fellows tested significantly better (P<.001), and
      they were the best in all 4 subcategories of competency, whereas MS1-2 were the
      worst in the auditory and visual subcategories. Participants demonstrated low
      specificity for systolic murmurs (0.35) and low sensitivity for diastolic murmurs
      (0.49). CONCLUSIONS: Cardiac examination skills do not improve after MS3 and may
      decline after years in practice, which has important implications for medical
      decision making, patient safety, cost-effective care, and continuing medical
      education. Improvement in cardiac examination competency will require training in
      simultaneous audio and visual examination in faculty and trainees.

PMID- 16567599
TI  - Relationship between accurate auscultation of a clinically useful third heart
      sound and level of experience.
AB  - BACKGROUND: Poor performance by physicians-in-training and interobserver
      variability between physicians have diminished clinicians' confidence in the
      value of the third heart sound (S3). METHODS: To determine whether auscultation
      of a clinically useful S3 improves with advancing levels of experience, we
      performed a prospective, blinded, observational study of 100 patients undergoing
      left-sided heart catheterization. Patients underwent blinded auscultation by 4
      physicians (each from 1 of 4 different levels of experience), phonocardiography,
      measurement of blood B-type natriuretic peptide levels, echocardiography for
      measurement of left ventricular ejection fraction, and cardiac catheterization
      for measurement of left ventricular end-diastolic pressure. RESULTS: Whereas
      residents' and interns' auscultatory findings demonstrated no significant
      agreement with phonocardiographic findings, an S3 auscultated by cardiology
      fellows (kappa = 0.37; P<.001) and cardiology attendings (kappa = 0.29; P = .003)
      agreed with phonocardiographic findings. Although the sensitivities of the S3
      were low (13%-52%) for identifying patients with abnormal measures of left
      ventricular function, the specificities were high (85%-95%), with the best test
      characteristics exhibited by phonocardiography and more experienced physicians.
      The S3 detected by attendings and fellows was superior in distinguishing an
      elevated B-type natriuretic peptide level, a depressed left ventricular ejection
      fraction, or an elevated left ventricular end-diastolic pressure (P = .002-.02
      for attendings and .02-.03 for fellows) compared with residents (P = .02-.47) or
      interns (P = .09-.64). CONCLUSIONS: The S3 auscultated by more experienced
      physicians demonstrated fair agreement with phonocardiographic findings. Although
      correlations were superior for phonocardiography, the associations between the S3
      and abnormal markers of left ventricular function improved with each level of
      auscultator experience.

PMID- 16567600
TI  - A trial of disclosing physicians' financial incentives to patients.
AB  - BACKGROUND: Concern regarding financial conflict of interest for physicians has
      led to calls for disclosure of financial incentives to patients. However, limited
      data on the outcomes of disclosure exist to guide policy. METHODS: This
      randomized trial was conducted among 8000 adult patients at 2 multispecialty
      group practices based in the Boston, Mass, and Los Angeles, Calif, areas.
      Intervention patients were mailed a compensation disclosure letter written by the
      chief medical officer of their physician group, and all patients were surveyed
      approximately 3 months later. RESULTS: Disclosure patients were significantly
      more able to identify correctly the compensation model of their primary care
      physician, in Boston (adjusted odds ratio, 2.30; 95% confidence interval, 1.92
      2.75) and in Los Angeles (adjusted odds ratio, 1.37; 95% confidence interval,
      1.03-1.82). Disclosure patients also had more confidence in their ability to
      judge the possible influence of incentives on their health care: in Boston, 32.5%
      vs 17.8% (P<.001); and in Los Angeles, 31.8% vs 26.4% (P = .20). The disclosure
      intervention did not change trust in primary care physicians overall. However, of
      patients who remembered receiving the disclosure, 21.4% in Boston and 24.4% in
      Los Angeles responded that the disclosure had increased trust either greatly or
      somewhat, while in both cities less than 5% of patients responded that the
      information decreased trust. Patients' loyalty to their physician group was
      higher among disclosure patients in Boston (73.4% vs 70.2%; P = .03) and Los
      Angeles (74.1% vs 66.9%; P = .08). CONCLUSIONS: Among diverse patient
      populations, a single mailed disclosure letter from physician groups was
      associated with improved knowledge of physicians' compensation models. Patients'
      trust in their physicians was unharmed, and their loyalty to their physician
      group was strengthened. For physician groups with similar compensation programs,
      disclosure to patients should be considered an effective method to enhance the
      patient-physician relationship.

PMID- 16567601
TI  - Associations between the age at diagnosis and location of colorectal cancer and
      the use of alcohol and tobacco: implications for screening.
AB  - BACKGROUND: Individualizing recommendations for colorectal cancer (CRC) screening
      intervals and modalities requires accurate risk assessment. Although hereditary
      predisposition is commonly used, the effect of exogenous risk factors has
      remained largely unexplored. To address this, we analyzed the age at presentation
      and location of CRC in relation to alcohol and tobacco use. METHODS: We queried
      the IMPAC Medical Registry Services Cancer Information Resource File for CRCs
      diagnosed between June 1, 1993, and December 31, 2003. Subjects were classified
      as current, past, or never users of alcohol and tobacco. A logistic regression
      model for location of CRC and a linear regression model for age at diagnosis were
      constructed using these explanatory variables along with gender, race, and
      insurance status. RESULTS: Our data set consisted of 161 172 patients with CRC.
      Current drinking, smoking, and smoking plus drinking were associated with younger
      ages at onset of CRC (adjusted age difference, 5.2, 5.2, and 7.8 years,
      respectively; P<.001 for all). A distal location of CRC was more likely to occur
      in current drinkers (odds ratio, 1.192; 95% confidence interval, 1.15-1.23) and
      smokers (odds ratio, 1.164; 95% confidence interval, 1.12-1.21). Colorectal
      cancer in men tended to occur earlier (adjusted age difference, 1.9 years;
      P<.001) and have a distal predominance (odds ratio, 1.42; P<.001) compared with
      women. The smoking but not the drinking effect size was greater in women than in
      men (adjusted age difference, 2.6 years; P<.001). CONCLUSIONS: Alcohol use,
      tobacco use, and male gender were associated with earlier onset and a distal
      location of CRC. If confirmed, these factors should guide recommendations
      regarding initiation of CRC screening and, possibly, choice of techniques.

PMID- 16567602
TI  - Current antibiotic therapy for isolated urinary tract infections in women.
AB  - BACKGROUND: Sulfa antibiotics, such as a combination product of trimethoprim and
      sulfamethoxazole, have traditionally been the drugs of choice for urinary tract
      infections (UTIs) and remained the most common treatment as recently as a decade
      ago. However, increasing sulfa resistance among Escherichia coli may have led to
      changes in prescribing practices. METHODS: We used the 2000-2002 National
      Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care
      Survey to obtain nationally representative data on antibiotics prescribed for
      women with isolated outpatient UTIs following visits to physicians' offices,
      hospital clinics, and emergency departments (n = 2638). Logistic regression was
      used to determine predictors of quinolone use. RESULTS: Quinolones were more
      commonly prescribed than sulfa antibiotics in each year evaluated. In the most
      recent year of data, quinolones were prescribed in 48% and sulfas in 33% of UTI
      visits (P<.04). Quinolones were significantly more likely to be prescribed to
      older patients and in visits occurring in the Northeast; however, no difference
      in quinolone prescribing was seen when evaluating insurance status, setting,
      race, ethnicity, health care provider type, and year. Approximately one third of
      the quinolones used were broader-spectrum agents. CONCLUSIONS: Quinolones have
      surpassed sulfas as the most common class of antibiotic prescribed for isolated
      outpatient UTI in women. Few significant predictors of quinolone use exist,
      suggesting that the increase is not confined to a certain subset of patients.
      This pervasive growth in quinolone use raises concerns about increases in
      resistance to this important class of antibiotics.

PMID- 16567603
TI  - Management of acute pharyngitis in adults: reliability of rapid streptococcal
      tests and clinical findings.
AB  - BACKGROUND: How to use clinical score, the rapid streptococcal antigen test
      (RSAT), and culture results is uncertain for efficient management of acute
      pharyngitis in adults. METHODS: This prospective cohort study included 372 adult
      patients with pharyngitis treated at a Swiss university-based primary care
      clinic. In eligible patients with 2 to 4 clinical symptoms and signs (temperature
      >or=38 degrees C, tonsillar exudate, tender cervical adenopathy, and no cough or
      rhinitis), we performed an RSAT and obtained a throat culture. We measured
      sensitivity and specificity of RSAT with culture as a gold standard and compared
      appropriate antibiotic use with cost per patient appropriately treated for the
      following 5 strategies: symptomatic treatment, systematic RSAT, selective RSAT,
      empirical antibiotic treatment, and systematic culture. RESULTS: RSAT had high
      sensitivity (91%) and specificity (95%) for the diagnosis of streptococcal
      pharyngitis. Systematic throat culture resulted in the highest antibiotic use, in
      38% of patients with streptococcal pharyngitis. Systematic RSAT led to nearly
      optimal treatment (94%) and antibiotic prescription (37%), with minimal
      antibiotic overuse (3%) and underuse (3%). Empirical antibiotic treatment in
      patients with 3 or 4 clinical symptoms or signs resulted in a lower rate of
      appropriate therapy (59%) but higher rates of antibiotic use (60%), overuse
      (32%), and underuse (9%). Systematic RSAT was more cost-effective than strategies
      based on empirical treatment or culture: 15.00 dollars, 26.00 dollars, and 32.00
      dollars, respectively, per patient appropriately treated. CONCLUSIONS: The RSAT
      we used is a valid test for diagnosis of pharyngitis in adults. A clinical
      approach combining this RSAT and clinical findings efficiently reduces
      inappropriate antibiotic prescription in adult patients with acute pharyngitis.
      Empirical therapy in patients with 3 or 4 clinical symptoms or signs results in
      antibiotic overuse.

PMID- 16567604
TI  - Prolonged effects of a home-based intervention in patients with chronic illness.
AB  - BACKGROUND: Data on the long-term benefits of nonspecific disease management
      programs are limited. We performed a long-term follow-up of a previously
      published randomized trial. METHODS: We compared all-cause mortality and
      recurrent hospitalization during median follow-up of 7.5 years in a heterogeneous
      cohort of patients with chronic illness initially exposed to a multidisciplinary,
      home-based intervention (HBI) (n = 260) or to usual postdischarge care (n = 268).
      RESULTS: During follow-up, HBI had no impact on all-cause mortality (relative
      risk, 1.04; 95% confidence interval, 0.80-1.35) or event-free survival from death
      or unplanned hospitalization (relative risk, 1.03; 95% confidence interval, 0.86
      1.24). Initial analysis suggested that HBI had only a marginal impact in reducing
      unplanned hospitalization, with 677 readmissions vs 824 for the usual care group
      (mean +/- SD rate, 0.72 +/- 0.96 vs 0.84 +/- 1.20 readmissions/patient per year;
      P = .08). When accounting for increased hospital activity in HBI patients with
      chronic obstructive pulmonary disease during follow-up for 2 years, post hoc
      analyses showed that HBI reduced readmissions by 14% within 2 years in patients
      without this condition (mean +/- SD rate, 0.54 +/- 0.72 vs 0.63 +/- 0.88
      readmission/patient per year; P = .04) and by 21% in all surviving patients
      within 3 to 8 years (mean +/- SD rate, 0.64 +/- 1.26 vs 0.81 +/- 1.61
      readmissions/patient per year; P = .03). Overall, recurrent hospital costs were
      significantly lower (14%) in the HBI group (mean +/- SD, 823 dollars +/- 1642
      dollars vs 960 dollars +/- 1376 dollars per patient per year; P = .045).
      CONCLUSION: This unique study suggests that a nonspecific HBI provides long-term
      cost benefits in a range of chronic illnesses, except for chronic obstructive
      pulmonary disease.

PMID- 16567605
TI  - Natural history of knee cartilage defects and factors affecting change.
AB  - BACKGROUND: Knee cartilage defects may play an important role in early
      osteoarthritis, but little is known about their natural history. METHODS: Knee
      cartilage defect score (range, 0-4), cartilage volume, and bone surface area were
      determined using T1-weighted fat-saturated magnetic resonance imaging in 325
      subjects (mean age, 45 years) at baseline and 2 years later. RESULTS: Thirty
      three percent of the subjects had a worsening (>or=1-point increase) and 37% of
      the subjects had an improvement (>or=1-point decrease) in cartilage defect score
      in any knee compartment during 2.3 years. A worsening in cartilage defect score
      was significantly associated with female sex (odds ratio [OR], 3.09 and 3.64 in
      the medial and lateral tibiofemoral compartments) and baseline factors, including
      age (OR, 1.05 per year in the medial tibiofemoral compartment), body mass index
      (OR, 1.08 in the lateral tibiofemoral compartment), tibiofemoral osteophytes (OR,
      6.22 and 6.04 per grade), tibial bone area (OR, 1.24 and 2.07 per square
      centimeter), and cartilage volume (OR, 2.91 and 1.71 per milliliter in the medial
      tibiofemoral and patellar compartments). An improvement in cartilage defect score
      had similar but reversed associations with these factors (except for sex),
      including a decrease in body mass index (OR, 1.23 in the medial tibiofemoral
      compartment). CONCLUSIONS: Knee cartilage defects are variable, and changes are
      associated with female sex, age, and body mass index. Increases are associated
      with baseline cartilage volume, bone size, and osteophytes, suggesting a role for
      these in the pathogenesis of cartilage defects. Interventions such as weight loss
      may improve knee cartilage defects.

PMID- 16567606
TI  - Effects of angiotensin-converting enzyme inhibition with perindopril on left
      ventricular remodeling and clinical outcome: results of the randomized
      Perindopril and Remodeling in Elderly with Acute Myocardial Infarction (PREAMI)
      Study.
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitors reduce mortality and
      remodeling after myocardial infarction in patients with left ventricular
      dysfunction. METHODS: Perindopril and Remodeling in Elderly With Acute Myocardial
      Infarction (PREAMI), a double-blind, randomized, parallel-group, multicenter,
      placebo-controlled study, determined whether similar benefits occur in elderly
      postinfarction patients with preserved left ventricular function. A total of 1252
      patients 65 years or older with a left ventricular ejection fraction of 40% or
      higher and recent acute myocardial infarction were randomized to receive
      perindopril erbumine or placebo (8 mg/d) for 12 months. The combined primary end
      point was death, hospitalization for heart failure, or left ventricular
      remodeling. Secondary end points included cardiovascular death, hospitalization
      for reinfarction or angina, and revascularization. RESULTS: The primary end point
      occurred in 181 patients (35%) taking perindopril and 290 patients (57%) taking
      placebo, with a significant absolute risk reduction of 0.22 (95% confidence
      interval, 0.16 to 0.28; P<.001). A total of 126 patients (28%) and 226 patients
      (51%) in the perindopril and placebo groups, respectively, experienced
      remodeling. The mean increase in left ventricle end-diastolic volume was 0.7 mL
      with perindopril compared with 4.0 mL with placebo (P<.001). In the perindopril
      group, 40 deaths (6%) and 22 hospitalizations (4%) for heart failure occurred,
      whereas 37 deaths (6%) and 30 hospitalizations (5%) occurred in the placebo
      group. Treatment did not affect death, whereas the hospitalization rate for heart
      failure was slightly reduced (absolute risk reduction, 0.01; 95% confidence
      interval, -0.01 to 0.02). No treatment effect on other secondary end points was
      detected. CONCLUSION: We found that 1-year treatment with 8 mg/d of perindopril
      reduces progressive left ventricular remodeling that can occur even in the
      presence of small infarct size, but it was not associated with better clinical
      outcomes.

PMID- 16567608
TI  - Effect of quality improvement on racial disparities in diabetes care.
AB  - BACKGROUND: Racial disparities in care are well documented; information regarding
      solutions is limited. We evaluated whether generic quality improvement efforts
      were associated with changes in racial disparities in diabetes care. METHODS:
      Using insurance claims and electronic medical record data, we identified 5101
      whites and 1987 blacks with diabetes mellitus receiving care within a
      multispecialty group practice from 1997 to 2001. We assessed rates of annual low
      density lipoprotein cholesterol level testing, low-density lipoprotein
      cholesterol level control (<130 mg/dL [<3.37 mmol/L]), statin therapy, annual
      glycosylated hemoglobin level testing, glycosylated hemoglobin level control
      (<7.0%), and annual dilated eye examinations. We used logistic regression models
      with generalized estimating equations to adjust for race, year, race x year
      interactions, age, and sex. RESULTS: Rates of annual low-density lipoprotein
      cholesterol level testing increased from 39% to 64%, while the white-black
      disparity decreased from 14% to 4%; rates of low-density lipoprotein cholesterol
      level control increased from 15% to 43%, while the white-black disparity
      decreased from 9% to 6% (P<.001 for both race x year interactions). Statin
      therapy rates increased from 20% to 37%; however, black patients remained less
      likely than white patients to receive therapy. The 1997 rates of annual
      glycosylated hemoglobin level testing (76%) and annual eye examinations (74%)
      were high, and there was no white-black disparity over time. Rates of
      glycosylated hemoglobin level control remained low (31%), and the white-black
      disparity remained constant at 10%. CONCLUSIONS: Racial disparities were
      diminished in some aspects of diabetes care following variably successful quality
      improvement, but differences in the use of statins and glycemic level control
      persisted. Reducing disparities may require a focus on minority health.

PMID- 16567607
TI  - A controlled trial of naltrexone augmentation of nicotine replacement therapy for
      smoking cessation.
AB  - BACKGROUND: Many smokers remain refractory to current therapies, which only
      partially address weight gain after smoking cessation. Thus, this study evaluated
      whether naltrexone hydrochloride augmentation of nicotine patch therapy improves
      smoking abstinence and reduces postcessation weight gain more than nicotine patch
      therapy alone and at what dose. METHODS: Six-week double-blind placebo-controlled
      trial with follow-up in an outpatient research center. Four hundred individuals
      who smoked 20 or more cigarettes daily were randomly assigned to treatment for 6
      weeks with a 21-mg nicotine patch and oral naltrexone hydrochloride (0, 25, 50,
      or 100 mg/d) after equal random treatment assignment and followed up for 1 year
      after randomization. The a priori specified primary end points were prolonged 4
      week cigarette abstinence after a 2-week grace period in the intent-to-treat
      sample and weight gain in these abstainers. RESULTS: We found no significant
      differences in prolonged 4-week abstinence (P = .49) or 6-week continuous
      abstinence after the quit date (P = .12) during treatment in the intent-to-treat
      analysis. Among 295 treatment completers, the 100-mg dose was associated with
      higher continuous abstinence rates (71.6%) compared with placebo (48%) (odds
      ratio, 2.73; 95% confidence interval, 1.39-5.39; P<.01). Among continuous
      abstainers, the 25-mg naltrexone hydrochloride group gained significantly less
      weight (mean +/- SEM, 0.7 +/- 0.31 kg) than the placebo group (mean +/- SEM, 1.9
      +/- 0.33 kg; P<.01). Similar naltrexone dose effects on weight were found for
      those with prolonged abstinence and treatment completers, irrespective of
      abstinence. CONCLUSIONS: The 100-mg dose of naltrexone hydrochloride appears the
      most promising for augmenting the efficacy of the nicotine patch on smoking
      cessation outcomes but requires further study. The significant weight reduction
      with low-dose naltrexone therapy suggests that it may be useful as a second-line
      treatment for weight-concerned smokers.

PMID- 16567609
TI  - Type 2 diabetes mellitus in midlife estimated from the Cambridge Risk Score and
      body mass index.
AB  - BACKGROUND: The Cambridge Risk Score (CRS) was developed to screen for type 2
      diabetes mellitus risk. We assessed the ability of the CRS to predict
      glycosylated hemoglobin (HbA(1c)) levels and determined whether the CRS was
      better than body mass index (BMI) at predicting HbA(1c) levels in midlife.
      METHODS: We included 7452 participants without known diabetes in a biomedical
      survey of the 1958 British Birth Cohort at 45 years of age. Receiver operator
      characteristic curves were used to compare the ability of the CRS and BMI to
      identify individuals with elevated HbA(1c) levels using thresholds of 7.0% or
      more, 6.0% or more, and 5.5% or more. RESULTS: Of the total sample, 0.9% (95%
      confidence interval [CI], 0.7%-1.1%) had HbA(1c) levels of 7.0% or more; 3.8%
      (95% CI, 3.2%-4.5%), 6.0% or more; and 24.4% (95% CI, 23.1%-25.9%), 5.5% or more.
      The CRS detected individuals with elevated HbA(1c) levels with reasonable
      accuracy (area under the curve, 0.84 for HbA(1c) level >or=7.0%; 0.76 for HbA(1c)
      level >or=6.0%). Similar area under the curve values were obtained using BMI
      alone (0.84 for HbA(1c) level >or=7.0%; 0.79 for HbA(1c) level >or=6.0%). When
      tested using the lower HbA(1c) threshold of 5.5% or more, the CRS and BMI did not
      perform well (areas under the curve, 0.65 and 0.63 for CRS and BMI,
      respectively). Both measures indicated that approximately 20% of the cohort were
      at increased risk of diabetes. Owing to the low prevalence of diabetes at 45
      years of age, only 2% to 3% of those considered at risk had elevated HbA(1c)
      levels. CONCLUSIONS: For a population in mid-adult life, the CRS identified
      individuals with elevated HbA(1c) levels reasonably well. However, the CRS had no
      advantage compared with BMI alone in identifying diabetes risk.

PMID- 16567610
TI  - Use of a blood glucose monitoring manual to enhance monitoring adherence in
      adults with diabetes: a randomized controlled trial.
AB  - BACKGROUND: Frequent blood glucose (BG) monitoring is a critical component of
      diabetes management, yet many barriers exist to consistent monitoring. METHODS:
      In this randomized controlled trial, we sought to determine if an educational
      manual, the Blood Sugar Monitoring Owner's Manual (BGMOM), could increase
      adherence to BG monitoring by helping patients form realistic expectations and
      responses to BG monitoring results. The 199 participants were recruited from a
      multidisciplinary diabetes clinic and had high-risk diabetes (hemoglobin A(1C)
      >or=8.0%); 35% had type 1 diabetes mellitus. Participants were randomized to 1 of
      3 groups: BGMOM intervention (BGM+), attention control (BG meter only [MT]), or
      standard care (SC). The BGM+ and MT groups received BG meters and meter
      education; the BGM+ group also received BGMOM booklets. The SC group received
      usual care. Data gathered during 6 months of follow-up included BG monitoring
      frequency and hemoglobin A(1C) measurement. RESULTS: Monitoring frequency
      increased significantly in the BGM+ group (1.9 +/- 1.3 to 2.8 +/- 1.5 times
      daily, P<.001) but only slightly in the MT group (1.7 +/- 1.3 to 2.0 +/- 1.3
      times daily). The BGM+ group experienced the greatest improvement in hemoglobin
      A(1C) level (BGM+: -0.13 +/- 1.28; MT: -0.04 +/- 1.31; SC: 0.04 +/- 1.10).
      Further, a higher percentage of those in the BGM+ group (61%) improved their
      glycemic control compared with the other groups (44%; P = .05). Finally, the BGM+
      group displayed the most knowledge about the definition of hemoglobin A(1C) (P =
      .04) and reported the least amount of negative affect about out-of-range BG
      monitoring results (P = .03). CONCLUSION: As an adjunct to standard diabetes
      education and support, a manual such as the BGMOM can help optimize BG monitoring
      and glycemic control.

PMID- 16567611
TI  - Colchicine for recurrent acute pericarditis.

PMID- 16567612
TI  - Complex haplotypes derived from noncoding polymorphisms of the intronless alpha2A
      adrenergic gene diversify receptor expression.
AB  - Alpha(2A)-adrenergic receptors (alpha(2A)AR) regulate multiple central nervous
      system, cardiovascular, and metabolic processes including neurotransmitter
      release, platelet aggregation, blood pressure, insulin secretion, and lipolysis.
      Complex diseases associated with alpha(2A)AR dysfunction display familial
      clustering, phenotypic heterogeneity, and interindividual variability in response
      to therapy targeted to alpha(2A)ARs, suggesting common, functional polymorphisms.
      In a multiethnic discovery cohort we identified 16 single-nucleotide
      polymorphisms (SNPs) in the alpha(2A)AR gene organized into 17 haplotypes of two
      major phylogenetic clades. In contrast to other adrenergic genes, variability of
      the alpha(2A)AR was primarily due to SNPs in the promoter, 5' UTR and 3' UTR, as
      opposed to the coding block. Marked ethnic variability in the frequency of SNPs
      and haplotypes was observed: one haplotype represented 70% of Caucasians, whereas
      Africans and Asians had a wide distribution of less common haplotypes, with the
      highest haplotype frequencies being 16% and 35%, respectively. Despite the
      compact nature of this intronless gene, local linkage disequilibrium between a
      number of SNPs was low and ethnic-dependent. Whole-gene transfections into BE(2)
      C human neuronal cells using vectors containing the entire approximately 5.3-kb
      gene without exogenous promoters were used to ascertain the effects of haplotypes
      on alpha(2A)AR expression. Substantial differences (P < 0.001) in transcript and
      cell-surface protein expression, by as much as approximately 5-fold, was observed
      between haplotypes, including those with common frequencies. Thus, signaling by
      this virtually ubiquitous receptor is under major genetic influence, which may be
      the basis for highly divergent phenotypes in complex diseases such as systemic
      and pulmonary hypertension, heart failure, diabetes, and obesity.

PMID- 16567613
TI  - Reelin expression and glycosylation patterns are altered in Alzheimer's disease.
AB  - Reelin is a glycoprotein that is essential for the correct cytoarchitectonic
      organization of the developing CNS. Its function in the adult brain is less
      understood, although it has been proposed that Reelin is involved in signaling
      pathways linked to neurodegeneration. Here we analyzed Reelin expression in
      brains and cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients and
      nondemented controls. We found a 40% increase in the Reelin protein levels in the
      cortex of AD patients compared with controls. Similar increases were detected at
      the Reelin mRNA transcriptional level. This expression correlates with parallel
      increases in CSF but not in plasma samples. Next, we examined whether CSF Reelin
      levels were also altered in neurological diseases, including frontotemporal
      dementia, progressive supranuclear palsy, and Parkinson's disease. The Reelin 180
      kDa band increased in all of the neurodegenerative disorders analyzed. Moreover,
      the 180-kDa Reelin levels correlated positively with Tau protein in CSF. Finally,
      we studied the pattern of Reelin glycosylation by using several lectins and the
      anti-HNK-1 antibody. Glycosylation differed in plasma and CSF. Furthermore, the
      pattern of Reelin lectin binding differed between the CSF of controls and in AD.
      Our results show that Reelin is up-regulated in the brain and CSF in several
      neurodegenerative diseases and that CSF and plasma Reelin have distinct cellular
      origins, thereby supporting that Reelin is involved in the pathogenesis of a
      number of neurodegenerative diseases.

PMID- 16567614
TI  - Songbirds tune their vocal tract to the fundamental frequency of their song.
AB  - In human speech, the sound generated by the larynx is modified by articulatory
      movements of the upper vocal tract, which acts as a variable resonant filter
      concentrating energy near particular frequencies, or formants, essential in
      speech recognition. Despite its potential importance in vocal communication,
      little is known about the presence of tunable vocal tract filters in other
      vertebrates. The tonal quality of much birdsong, in which upper harmonics have
      relatively little energy, depends on filtering of the vocal source, but the
      nature of this filter is controversial. Current hypotheses treat the songbird
      vocal tract as a rigid tube with a resonance that is modulated by the end
      correction of a variable beak opening. Through x-ray cinematography of singing
      birds, we show that birdsong is accompanied by cyclical movements of the hyoid
      skeleton and changes in the diameter of the cranial end of the esophagus that
      maintain an inverse relationship between the volume of the oropharyngeal cavity
      and esophagus and the song's fundamental frequency. A computational acoustic
      model indicates that this song-related motor pattern tunes the major resonance of
      the oropharyngeal-esophageal cavity to actively track the song's fundamental
      frequency.

PMID- 16567615
TI  - Specific T-type calcium channel isoforms are associated with distinct burst
      phenotypes in deep cerebellar nuclear neurons.
AB  - T-type calcium channels are thought to transform neuronal output to a burst mode
      by generating low voltage-activated (LVA) calcium currents and rebound burst
      discharge. In this study we assess the expression pattern of the three different
      T-type channel isoforms (Ca(v)3.1, Ca(v)3.2, and Ca(v)3.3) in cerebellar neurons
      and focus on their potential role in generating LVA spikes and rebound discharge
      in deep cerebellar nuclear (DCN) neurons. We detected expression of one or more
      Ca(v)3 channel isoforms in a wide range of cerebellar neurons and selective
      expression of different isoforms in DCN cells. We further identify two classes of
      large-diameter DCN neurons that exhibit either a strong or weak capability for
      rebound discharge, despite the ability to generate LVA spikes when calcium
      currents are pharmacologically isolated. By correlating the Ca(v)3 channel
      expression pattern with the electrophysiological profile of identified DCN cells,
      we show that Ca(v)3.1 channels are expressed in isolation in DCN-burst cells,
      whereas Ca(v)3.3 is expressed in DCN-weak burst cells. Ca(v)3.1-expressing DCN
      cells correspond to excitatory or GABAergic neurons, whereas Ca(v)3.3-expressing
      cells are non-GABAergic. The Ca(v)3 class of LVA calcium channels is thus
      expressed in specific combinations in a wide range of cerebellar neurons but
      contributes to rebound burst discharge in only a select number of cell classes.

PMID- 16567616
TI  - The influence of chromosome flexibility on chromosome transport during anaphase
      A.
AB  - The role of protein flexibility in molecular motor function has previously been
      studied by considering a Brownian ratchet motor that is connected to its cargo by
      an elastic spring, with the result that the average velocity of the motor/cargo
      system is increased by reducing the stiffness of the linkage. Here, we extend
      this investigation to the case of chromosome transport during anaphase A, in
      which the relevant flexibility is not primarily in the motor/cargo linkage but
      rather in the cargo itself, i.e., in the chromosome. We model the motor mechanism
      as an imperfect Brownian ratchet with a built-in opposing load and the chromosome
      as a collection of discrete segments linked by an elastic energy function that
      discretizes the potential energy of an elastic rod. Thermal fluctuations are
      produced in the model by random forces, as in Brownian dynamics. All of the
      parameters that characterize the chromosome are known or can be estimated from
      experimental data, as can all but one of the motor parameters, which is adjusted
      to give the correct transport velocity of normal-length chromosomes. With the
      parameters so determined, we then reproduce the experimental finding of Nicklas
      [Nicklas, R. B. (1965) J. Cell Biol. 25, 119-135] that chromosome speed is
      essentially independent of chromosome length, even though our model contains no
      "velocity governor." We find instead that this effect is a consequence of
      chromosome flexibility, as it disappears when stiffer than normal chromosomes are
      considered.

PMID- 16567617
TI  - NifB-dependent in vitro synthesis of the iron-molybdenum cofactor of nitrogenase.
AB  - Biological nitrogen fixation, an essential process of the biogeochemical nitrogen
      cycle that supports life on Earth, is catalyzed by the nitrogenase enzyme. The
      nitrogenase active site contains an iron and molybdenum cofactor (FeMo-co)
      composed of 7Fe-9S-Mo-homocitrate and one not-yet-identified atom, which probably
      is the most complex [Fe-S] cluster in nature. Here, we show the in vitro
      synthesis of FeMo-co from its simple constituents, Fe, S, Mo, and homocitrate.
      The in vitro FeMo-co synthesis requires purified NifB and depends on S
      adenosylmethionine, indicating that radical chemistry is required during FeMo-co
      assembly.

PMID- 16567618
TI  - Transfer characteristics of the hair cell's afferent synapse.
AB  - The sense of hearing depends on fast, finely graded neurotransmission at the
      ribbon synapses connecting hair cells to afferent nerve fibers. The processing
      that occurs at this first chemical synapse in the auditory pathway determines the
      quality and extent of the information conveyed to the central nervous system.
      Knowledge of the synapse's input-output function is therefore essential for
      understanding how auditory stimuli are encoded. To investigate the transfer
      function at the hair cell's synapse, we developed a preparation of the bullfrog's
      amphibian papilla. In the portion of this receptor organ representing stimuli of
      400-800 Hz, each afferent nerve fiber forms several synaptic terminals onto one
      to three hair cells. By performing simultaneous voltage-clamp recordings from
      presynaptic hair cells and postsynaptic afferent fibers, we established that the
      rate of evoked vesicle release, as determined from the average postsynaptic
      current, depends linearly on the amplitude of the presynaptic Ca(2+) current.
      This result implies that, for receptor potentials in the physiological range, the
      hair cell's synapse transmits information with high fidelity.

PMID- 16567619
TI  - NXP-2 association with SUMO-2 depends on lysines required for transcriptional
      repression.
AB  - Small ubiquitin-like modifier (SUMO) modification of transcription factors is
      generally associated with repression. Reverse genetic analysis of SUMO-1, and -2
      conserved residues emphasized the importance of dual charge reversals in
      abrogating the critical role of SUMO-2 K33, K35, and K42 in repression. GST-SUMO
      2-affinity chromatography followed by liquid chromatography (LC)-MS analysis
      identified proteins that appeared to bind preferentially to WT SUMO-2 versus SUMO
      2 K33E and K35E. LSD1, NXP-2, KIAA0809 (ARIP4), SAE2, RanGAP1, PELP1, and SETDB1
      bound to SUMO-2 and not to SUMO-2 K33E, K42E, or K35E and K42E. Although LSD1 is
      a histone lysine demethylase, and histone H3K4 was demethylated at a SUMO-2
      repressed promoter, neither overexpression of a dominant-negative LSD1 nor LSD1
      depletion with RNA interference affected SUMO-2-mediated repression, indicating
      that LSD1 is not essential for repression, in this context. When tethered to a
      promoter by fusion to Gal4, NXP-2 repressed transcription, consistent with a role
      for NXP-2 in SUMO-mediated repression. SUMO-2-associated proteins identified in
      this study may contribute to SUMO-dependent regulation of transcription or other
      processes.

PMID- 16567620
TI  - A protein interaction surface in nonribosomal peptide synthesis mapped by
      combinatorial mutagenesis and selection.
AB  - Nonribosomal peptide synthetases (NRPSs) and polyketide synthases are large,
      multidomain enzymes that biosynthesize a number of pharmaceutically important
      natural products. The recognition of biosynthetic intermediates, displayed via
      covalent attachment to carrier proteins, by catalytic domains is critical for
      NRPS and polyketide synthase function. We report the use of combinatorial
      mutagenesis coupled with in vivo selection for the production of the Escherichia
      coli NRPS product enterobactin to map the surface of the aryl carrier protein
      (ArCP) domain of EntB that interacts with the downstream elongation module EntF.
      Two libraries spanning the predicted helix 2 and loop 2/helix 3 of EntB-ArCP were
      generated by shotgun alanine scanning and selected for their ability to support
      enterobactin production. From the surviving pools, we identified several
      hydrophobic residues (M249, F264, and A268) that were highly conserved. These
      residues cluster near the phosphopantetheinylated serine in a structural model,
      and two of these positions are in the predicted helix 3 region. Subsequent in
      vitro studies are consistent with the hypothesis that these residues form a
      surface on EntB required for interaction with EntF. These results suggest that
      helix 3 is a major recognition element in EntB-ArCP and demonstrate the utility
      of selection-based approaches for studying NRPS biosynthesis.

PMID- 16567623
TI  - Green primaries: environmentally friendly energetic complexes.
AB  - Primary explosives are used in small quantities to generate a detonation wave
      when subjected to a flame, heat, impact, electric spark, or friction. Detonation
      of the primary explosive initiates the secondary booster or main-charge explosive
      or propellant. Long-term use of lead azide and lead styphnate as primary
      explosives has resulted in lead contamination at artillery and firing ranges and
      become a major health hazard and environmental problem for both military and
      civilian personnel. Devices using lead primary explosives are manufactured by the
      tens of millions every year in the United States from primers for bullets to
      detonators for mining. Although substantial synthetic efforts have long been
      focused on the search for greener primary explosives, this unresolved problem has
      become a "holy grail" of energetic materials research. Existing candidates suffer
      from instability or excessive sensitivity, or they possess toxic metals or
      perchlorate. We report here four previously undescribed green primary explosives
      based on complex metal dianions and environmentally benign cations,
      (cat)(2)[M(II)(NT)(4)(H(2)O)(2)] (where cat is NH(4)(+) or Na(+), M is Fe(2+) or
      Cu(2+), and NT(-) is 5-nitrotetrazolato-N(2)). They are safer to prepare, handle,
      and transport than lead compounds, have comparable initiation efficiencies to
      lead azide, and offer rapid reliable detonation comparable with lead styphnate.
      Remarkably, they possess all current requirements for green primary explosives
      and are suitable to replace lead primary explosives in detonators. More
      importantly, they can be synthesized more safely, do not pose health risks to
      personnel, and cause much less pollution to the environment.

PMID- 16567621
TI  - Bottleneck-mediated quasispecies restriction during spread of an RNA virus from
      inoculation site to brain.
AB  - The amplification of RNA viruses such as poliovirus is associated with high error
      rates, and the resulting diversity likely facilitates viral survival within an
      infected host. However, within individual tissues of infected hosts, there may be
      barriers to viral spread that limit genome sampling. We tested whether poliovirus
      population diversity was maintained during viral spread to the brain of
      poliovirus receptor-expressing mice. Each of four restriction enzyme site-tagged
      viruses was shown to be able to replicate in the mouse brain. However, when
      infection was initiated by i.m., i.v., or i.p. routes, only a subset of the
      members of the injected pool was detectable in the brain. This jackpot effect was
      the result of a bottleneck in viral transit from the inoculation site to the
      brain. The bottleneck was difficult to overcome, requiring a 10(7) increase in
      viral inoculum to allow representation of all or most members of the infecting
      pool. Therefore, the bottleneck is not likely to be a physical barrier but an
      antiviral state induced by a founder virus. We suggest that the innate immune
      response can limit viral pathogenicity by limiting the number and therefore the
      diversity of viruses during spread to vulnerable tissues.

PMID- 16567622
TI  - Insights into transcriptional regulation and sigma competition from an
      equilibrium model of RNA polymerase binding to DNA.
AB  - To explore scenarios that permit transcription regulation by activator
      recruitment of RNA polymerase and sigma competition in vivo, we used an
      equilibrium model of RNA polymerase binding to DNA constrained by the values of
      total RNA polymerase (E) and sigma(70) per cell measured in this work. Our
      numbers of E and sigma(70) per cell, which are consistent with most of the
      primary data in the literature, suggest that in vivo (i) only a minor fraction of
      RNA polymerase (<20%) is involved in elongation and (ii) sigma(70) is in excess
      of total E. Modeling the partitioning of RNA polymerase between promoters,
      nonspecific DNA binding sites, and the cytoplasm suggested that even weak
      promoters will be saturated with Esigma(70) in vivo unless nonspecific DNA
      binding by Esigma(70) is rather significant. In addition, the model predicted
      that sigmas compete for binding to E only when their total number exceeds the
      total amount of RNA polymerase (excluding that involved in elongation) and that
      weak promoters will be preferentially subjected to sigma competition.

PMID- 16567624
TI  - Suppression of prion protein in livestock by RNA interference.
AB  - Given the difficulty of applying gene knockout technology to species other than
      mice, we decided to explore the utility of RNA interference (RNAi) in silencing
      the expression of genes in livestock. Short hairpin RNAs (shRNAs) were designed
      and screened for their ability to suppress the expression of caprine and bovine
      prion protein (PrP). Lentiviral vectors were used to deliver a transgene
      expressing GFP and an shRNA targeting PrP into goat fibroblasts. These cells were
      then used for nuclear transplantation to produce a cloned goat fetus, which was
      surgically recovered at 81 days of gestation and compared with an age-matched
      control derived by natural mating. All tissues examined in the cloned fetus
      expressed GFP, and PCR analysis confirmed the presence of the transgene encoding
      the PrP shRNA. Most relevant, Western blot analysis performed on brain tissues
      comparing the transgenic fetus with control demonstrated a significant (>90%)
      decrease in PrP expression levels. To confirm that similar methodologies could be
      applied to the bovine, recombinant virus was injected into the perivitelline
      space of bovine ova. After in vitro fertilization and culture, 76% of the
      blastocysts exhibited GFP expression, indicative that they expressed shRNAs
      targeting PrP. Our results provide strong evidence that the approach described
      here will be useful in producing transgenic livestock conferring potential
      disease resistance and provide an effective strategy for suppressing gene
      expression in a variety of large-animal models.

PMID- 16567626
TI  - Profile of Peter Walter.

PMID- 16567627
TI  - Profile of Robert M. Stroud.

PMID- 16567628
TI  - The inherent structure landscape of a protein.
AB  - Using the Go model of a real protein, we explore the landscape of its metastable
      structures. First, we show how the inherent structure energy density can be
      obtained from the probability density determined by sampling molecular dynamics
      trajectories and quenching. The analysis of the inherent structure landscape can
      characterize the folding transition. Then we show how thermodynamics of the
      inherent states can be established to study the equilibrium properties of
      proteins. Our work brings some elements into the current discussion about the
      protein dynamical transition. The study uses a simplified model to illustrate the
      ideas, but, as the inherent structure landscape is much simpler than the free
      energy surface of the protein, it appears to be accessible for an all-atom model
      of a small protein, at the expense of much longer calculations.

PMID- 16567629
TI  - L-tartaric acid synthesis from vitamin C in higher plants.
AB  - The biosynthetic pathway of L-tartaric acid, the form most commonly encountered
      in nature, and its catabolic ties to vitamin C, remain a challenge to plant
      scientists. Vitamin C and L-tartaric acid are plant-derived metabolites with
      intrinsic human value. In contrast to most fruits during development, grapes
      accumulate L-tartaric acid, which remains within the berry throughout ripening.
      Berry taste and the organoleptic properties and aging potential of wines are
      intimately linked to levels of L-tartaric acid present in the fruit, and those
      added during vinification. Elucidation of the reactions relating L-tartaric acid
      to vitamin C catabolism in the Vitaceae showed that they proceed via the
      oxidation of L-idonic acid, the proposed rate-limiting step in the pathway. Here
      we report the use of transcript and metabolite profiling to identify candidate
      cDNAs from genes expressed at developmental times and in tissues appropriate for
      L-tartaric acid biosynthesis in grape berries. Enzymological analyses of one
      candidate confirmed its activity in the proposed rate-limiting step of the direct
      pathway from vitamin C to tartaric acid in higher plants. Surveying organic acid
      content in Vitis and related genera, we have identified a non-tartrate-forming
      species in which this gene is deleted. This species accumulates in excess of
      three times the levels of vitamin C than comparably ripe berries of tartrate
      accumulating species, suggesting that modulation of tartaric acid biosynthesis
      may provide a rational basis for the production of grapes rich in vitamin C.

PMID- 16567625
TI  - Apolipoprotein E4: a causative factor and therapeutic target in neuropathology,
      including Alzheimer's disease.
AB  - The premise of this review is that apolipoprotein (apo) E4 is much more than a
      contributing factor to neurodegeneration. ApoE has critical functions in
      redistributing lipids among CNS cells for normal lipid homeostasis, repairing
      injured neurons, maintaining synapto-dendritic connections, and scavenging
      toxins. In multiple pathways affecting neuropathology, including Alzheimer's
      disease, apoE acts directly or in concert with age, head injury, oxidative
      stress, ischemia, inflammation, and excess amyloid beta peptide production to
      cause neurological disorders, accelerating progression, altering prognosis, or
      lowering age of onset. We envision that unique structural features of apoE4 are
      responsible for apoE4-associated neuropathology. Although the structures of
      apoE2, apoE3, and apoE4 are in dynamic equilibrium, apoE4, which is detrimental
      in a variety of neurological disorders, is more likely to assume a pathological
      conformation. Importantly, apoE4 displays domain interaction (an interaction
      between the N- and C-terminal domains of the protein that results in a compact
      structure) and molten globule formation (the formation of stable, reactive
      intermediates with potentially pathological activities). In response to CNS
      stress or injury, neurons can synthesize apoE. ApoE4 uniquely undergoes neuron
      specific proteolysis, resulting in bioactive toxic fragments that enter the
      cytosol, alter the cytoskeleton, disrupt mitochondrial energy balance, and cause
      cell death. Our findings suggest potential therapeutic strategies, including the
      use of "structure correctors" to convert apoE4 to an "apoE3-like" molecule,
      protease inhibitors to prevent the generation of toxic apoE4 fragments, and
      "mitochondrial protectors" to prevent cellular energy disruption.

PMID- 16567630
TI  - Structural basis of docking interactions between ERK2 and MAP kinase phosphatase
      3.
AB  - Mitogen-activated protein (MAP) kinases are central components of signal
      transduction pathways for cell proliferation, stress responses, and
      differentiation. Signaling efficiency and specificity are modulated in large part
      by docking interactions between individual MAP kinase and the kinase interaction
      motif (KIM), (R/K)(2-3)-X(1-6)-Phi(A)-X-Phi(B), in its cognate kinases,
      phosphatases, scaffolding proteins, and substrates. We have determined the
      crystal structure of extracellular signal-regulated protein kinase 2 bound to the
      KIM peptide from MAP kinase phosphatase 3, an extracellular signal-regulated
      protein kinase 2-specific phosphatase. The structure reveals that the KIM docking
      site, situated in a noncatalytic region opposite of the kinase catalytic pocket,
      is comprised of a highly acidic patch and a hydrophobic groove, which engage the
      basic and Phi(A)-X-Phi(B) residues, respectively, in the KIM sequence. The
      specific docking interactions observed in the structure consolidate all known
      biochemical data. In addition, structural comparison indicates that the KIM
      docking site is conserved in all MAP kinases. The results establish a structural
      model for understanding how MAP kinases interact with their regulators and
      substrates and provide new insights into how MAP kinase docking specificity can
      be achieved.

PMID- 16567631
TI  - Na+/H+ exchanger type 1 is a receptor for pathogenic subgroup J avian leukosis
      virus.
AB  - Subgroup J avian leukosis virus (ALV-J) is a recently identified avian oncogenic
      retrovirus responsible for severe economic losses worldwide. In contrast with the
      other ALV subgroups, ALV-J predominantly induces myeloid leukosis in meat-type
      chickens. Despite significant homology with the other ALV subgroups across most
      of the genome, the envelope protein of ALV-J (EnvJ) shares low homology with the
      others. Pathogenicity and myeloid leukosis induction map to the env gene of ALV
      J. A chimeric protein composed of the surface domain of EnvJ fused to the
      constant region of a rabbit IgG and mass spectrometry were used to identify the
      chicken Na(+)/H(+) exchanger type 1 (chNHE1) as a binding protein for ALV-J. Flow
      cytometry analysis and coprecipitation experiments demonstrated a specific
      interaction between EnvJ and chNHE1. When introduced into nonpermissive human
      293T cells and quail QT6 cells, chNHE1 conferred susceptibility to EnvJ-mediated
      infection. Furthermore, 293T cells expressing chNHE1 fused with 293T cells
      expressing EnvJ in a low-pH-dependent manner. Together, these data identify
      chNHE1 as a cellular receptor for the highly pathogenic ALV-J.

PMID- 16567632
TI  - Hyperaccumulation of arsenic in the shoots of Arabidopsis silenced for arsenate
      reductase (ACR2).
AB  - Endogenous plant arsenate reductase (ACR) activity converts arsenate to arsenite
      in roots, immobilizing arsenic below ground. By blocking this activity, we hoped
      to construct plants that would mobilize more arsenate aboveground. We have
      identified a single gene in the Arabidopsis thaliana genome, ACR2, with moderate
      sequence homology to yeast arsenate reductase. Expression of ACR2 cDNA in
      Escherichia coli complemented the arsenate-resistant and arsenate-sensitive
      phenotypes of various bacterial ars operon mutants. RNA interference reduced ACR2
      protein expression in Arabidopsis to as low as 2% of wild-type levels. The
      various knockdown plant lines were more sensitive to high concentrations of
      arsenate, but not arsenite, than wild type. The knockdown lines accumulated 10-
      to 16-fold more arsenic in shoots (350-500 ppm) and retained less arsenic in
      roots than wild type, when grown on arsenate medium with <8 ppm arsenic. Reducing
      expression of ACR2 homologs in tree, shrub, and grass species should play a vital
      role in the phytoremediation of environmental arsenic contamination.

PMID- 16567633
TI  - The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal
      cystogenesis in polycystic kidney disease.
AB  - Autosomal-dominant polycystic kidney disease (ADPKD) is a common genetic disorder
      that frequently leads to renal failure. Mutations in polycystin-1 (PC1) underlie
      most cases of ADPKD, but the function of PC1 has remained poorly understood. No
      preventive treatment for this disease is available. Here, we show that the
      cytoplasmic tail of PC1 interacts with tuberin, and the mTOR pathway is
      inappropriately activated in cyst-lining epithelial cells in human ADPKD patients
      and mouse models. Rapamycin, an inhibitor of mTOR, is highly effective in
      reducing renal cystogenesis in two independent mouse models of PKD. Treatment of
      human ADPKD transplant-recipient patients with rapamycin results in a significant
      reduction in native polycystic kidney size. These results indicate that PC1 has
      an important function in the regulation of the mTOR pathway and that this pathway
      provides a target for medical therapy of ADPKD.

PMID- 16567635
TI  - Structural basis for histone N-terminal recognition by human peptidylarginine
      deiminase 4.
AB  - Histone arginine methylation is a posttranslational modification linked to the
      regulation of gene transcription. Unlike other posttranslational modifications,
      methylation has generally been regarded as stable, and enzymes that demethylate
      histone arginine residues have not been identified. However, it has recently been
      shown that human peptidylarginine deiminase 4 (PAD4), a Ca(2+)-dependent enzyme
      previously known to convert arginine residues to citrulline in histones, can also
      convert monomethylated arginine residues to citrulline both in vivo and in vitro.
      Citrullination of histone arginine residues by the enzyme antagonizes methylation
      by histone arginine methyltransferases and is thus a novel posttranslational
      modification that regulates the level of histone arginine methylation and gene
      activity. Here we present the crystal structures of a Ca(2+)-bound PAD4 mutant in
      complex with three histone N-terminal peptides, each consisting of 10 amino acid
      residues that include one target arginine residue for the enzyme (H3/Arg-8,
      H3/Arg-17, and H4/Arg-3). To each histone N-terminal peptide, the enzyme induces
      a beta-turn-like bent conformation composed of five successive residues at the
      molecular surface near the active site cleft. The remaining five residues are
      highly disordered. The enzyme recognizes each peptide through backbone atoms of
      the peptide with a possible consensus recognition motif. The sequence specificity
      of the peptide recognized by this enzyme is thought to be fairly broad. These
      observations provide structural insights into target protein recognition by
      histone modification enzymes and illustrate how PAD4 can target multiple arginine
      sites in the histone N-terminal tails.

PMID- 16567634
TI  - Substrate binding in quinoprotein ethanol dehydrogenase from Pseudomonas
      aeruginosa studied by electron-nuclear double resonance.
AB  - Binding of methanol to the quinoprotein ethanol dehydrogenase from Pseudomonas
      aeruginosa has been studied by pulsed electron-nuclear double resonance at 9 GHz.
      Shifts in the hyperfine couplings of the pyrroloquinoline quinone radical provide
      direct evidence for a change in the environment of the cofactor when substrate is
      present. By performing experiments with deuteriated methanol, we confirmed that
      methanol was the cause of the effect. Density functional theory calculations show
      that these shifts can be understood if a water molecule, which is often found in
      x-ray structures of the active site of quinoprotein alcohol dehydrogenases, is
      displaced by the substrate. The difference between the binding of water and
      methanol is that the water molecule forms a hydrogen bond to O5 of
      pyrroloquinoline quinone, which the methanol, by virtue of its methyl group, does
      not. The results support the proposal that aspartate rather than glutamate is the
      catalytically active base for a hydride transfer mechanism in quinoprotein
      alcohol dehydrogenases.

PMID- 16567636
TI  - Role of the Yersinia pestis plasminogen activator in the incidence of distinct
      septicemic and bubonic forms of flea-borne plague.
AB  - Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized
      by severe local lymphadenitis that progresses rapidly to systemic infection and
      life-threatening septicemia. Here, we show that although flea-borne transmission
      usually leads to bubonic plague in mice, it can also lead to primary septicemic
      plague. However, intradermal injection of Y. pestis, commonly used to mimic
      transmission by fleabite, leads only to bubonic plague. A Y. pestis strain
      lacking the plasmid-encoded cell-surface plasminogen activator, which is
      avirulent by intradermal or s.c. injection, was able to cause fatal primary
      septicemic plague at low incidence, but not bubonic plague, when transmitted by
      fleas. The results clarify a long-standing uncertainty about the etiology of
      primary septicemic plague and support an evolutionary scenario in which plague
      first emerged as a flea-borne septicemic disease of limited transmissibility.
      Subsequent acquisition of the plasminogen activator gene by horizontal transfer
      enabled the bubonic form of disease and increased the potential for epidemic
      spread.

PMID- 16567637
TI  - In vivo diffusion analysis with quantum dots and dextrans predicts the width of
      brain extracellular space.
AB  - Diffusion within the extracellular space (ECS) of the brain is necessary for
      chemical signaling and for neurons and glia to access nutrients and therapeutics;
      however, the width of the ECS in living tissue remains unknown. We used
      integrative optical imaging to show that dextrans and water-soluble quantum dots
      with Stokes-Einstein diameters as large as 35 nm diffuse within the ECS of adult
      rat neocortex in vivo. Modeling the ECS as fluid-filled "pores" predicts a normal
      width of 38-64 nm, at least 2-fold greater than estimates from EM of fixed
      tissue. ECS width falls below 10 nm after terminal ischemia, a likely explanation
      for the small ECS visualized in electron micrographs. Our results will improve
      modeling of neurotransmitter spread after spillover and ectopic release and
      establish size limits for diffusion of drug delivery vectors such as viruses,
      liposomes, and nanoparticles in brain ECS.

PMID- 16567638
TI  - Physically realistic homology models built with ROSETTA can be more accurate than
      their templates.
AB  - We have developed a method that combines the ROSETTA de novo protein folding and
      refinement protocol with distance constraints derived from homologous structures
      to build homology models that are frequently more accurate than their templates.
      We test this method by building complete-chain models for a benchmark set of 22
      proteins, each with 1 or 2 candidate templates, for a total of 39 test cases. We
      use structure-based and sequence-based alignments for each of the test cases. All
      atoms, including hydrogens, are represented explicitly. The resulting models
      contain approximately the same number of atomic overlaps as experimentally
      determined crystal structures and maintain good stereochemistry. The most
      accurate models can be identified by their energies, and in 22 of 39 cases a
      model that is more accurate than the template over aligned regions is one of the
      10 lowest-energy models.

PMID- 16567639
TI  - Suppression of natural killer cell-mediated bone marrow cell rejection by
      CD4+CD25+ regulatory T cells.
AB  - Naturally occurring CD4(+)CD25(+) T regulatory (Treg) cells have been shown to
      inhibit adaptive responses by T cells. Natural killer (NK) cells represent an
      important component of innate immunity in both cancer and infectious disease
      states. We investigated whether CD4(+)CD25(+) Treg cells could affect NK cell
      function in vivo by using allogeneic (full H2-disparate) bone marrow (BM)
      transplantation and the model of hybrid resistance, in which parental marrow
      grafts are rejected solely by the NK cells of irradiated (BALB/c x C57BL/6) F(1)
      recipients. We demonstrate that the prior removal of host Treg cells, but not
      CD8(+) T cells, significantly enhanced NK cell-mediated BM rejection in both
      models. The inhibitory role of Treg cells on NK cells was confirmed in vivo with
      adoptive transfer studies in which transferred CD4(+)CD25(+) cells could abrogate
      NK cell-mediated hybrid resistance. Anti-TGF-beta mAb treatment also increased NK
      cell-mediated BM graft rejection, suggesting that the NK cell suppression is
      exerted through TGF-beta. Thus, CD4(+)CD25(+) Treg cells can potently inhibit NK
      cell function in vivo, and their depletion may have therapeutic ramifications for
      NK cell function in BM transplantation and cancer therapy.

PMID- 16567640
TI  - Mitogen-activated protein kinase kinase 3 is a pivotal pathway regulating p38
      activation in inflammatory arthritis.
AB  - p38 mitogen-activated protein kinase (MAPK) regulates cytokines in arthritis and
      is, in turn, regulated by MAPK kinase (MKK) 3 and MKK6. To modulate p38 function
      but potentially minimize toxicity, we evaluated the utility of targeting MKK3 by
      using MKK3(-/-) mice. These studies showed that TNF-alpha increased
      phosphorylation of p38 in WT cultured synoviocytes but that p38 activation, IL
      1beta, and IL-6 expression were markedly lower in MKK3(-/-) synoviocytes. In
      contrast, IL-1beta or LPS-stimulated p38 phosphorylation and IL-6 production by
      MKK3(-/-) synoviocytes were normal. Detailed signaling studies showed that NF
      kappaB also contributes to IL-6 production and that TNF-alpha-induced NF-kappaB
      activation is MKK3-dependent. In contrast, LPS-mediated activation of NF-kappaB
      does not require MKK3. To determine whether this dichotomy occurs in vivo, two
      inflammation models were studied. In K/BxN passive arthritis, the severity of
      arthritis was dramatically lower in MKK3(-/-) mice. Phospho-p38, phospho-MAPK
      activator protein kinase 2, IL-1beta, CXC ligand 1, IL-6, and matrix
      metalloproteinase (MMP) 3 levels in the joints of MKK3(-/-) mice were
      significantly lower than in controls. Exogenous IL-1beta administered during the
      first 4 days of the passive model restored arthritis to the same severity as in
      WT mice. In the second model, IL-6 production after systemic LPS administration
      was similar in WT and MKK3(-/-) mice. Therefore, selective MKK3 deficiency can
      suppress inflammatory arthritis and cytokine production while Toll-like receptor
      4-mediated host defense remains intact.

PMID- 16567641
TI  - Glucocorticoids reduce phobic fear in humans.
AB  - Phobias are characterized by excessive fear, cued by the presence or anticipation
      of a fearful situation. Whereas it is well established that glucocorticoids are
      released in fearful situations, it is not known whether these hormones, in turn,
      modulate perceived fear. As extensive evidence indicates that elevated
      glucocorticoid levels impair the retrieval of emotionally arousing information,
      they might also inhibit retrieval of fear memory associated with phobia and,
      thereby, reduce phobic fear. Here, we investigated whether acutely administrated
      glucocorticoids reduced phobic fear in two double-blind, placebo-controlled
      studies in 40 subjects with social phobia and 20 subjects with spider phobia. In
      the social phobia study, cortisone (25 mg) administered orally 1 h before a socio
      evaluative stressor significantly reduced self-reported fear during the
      anticipation, exposure, and recovery phase of the stressor. Moreover, the stress
      induced release of cortisol in placebo-treated subjects correlated negatively
      with fear ratings, suggesting that endogenously released cortisol in the context
      of a phobic situation buffers fear symptoms. In the spider phobia study, repeated
      oral administration of cortisol (10 mg), but not placebo, 1 h before exposure to
      a spider photograph induced a progressive reduction of stimulus-induced fear.
      This effect was maintained when subjects were exposed to the stimulus again 2
      days after the last cortisol administration, suggesting that cortisol may also
      have facilitated the extinction of phobic fear. Cortisol treatment did not reduce
      general, phobia-unrelated anxiety. In conclusion, the present findings in two
      distinct types of phobias indicate that glucocorticoid administration reduces
      phobic fear.

PMID- 16567642
TI  - Simple and accurate estimation of ancestral protein sequences.
AB  - There are a variety of reasons to reconstruct the sequences of ancient proteins,
      but whatever the reason, the value of the reconstructed protein depends on the
      accuracy with which the ancient sequence is inferred. This study uses sequences
      simulated by a sequence-evolution simulation program that compares parsimony,
      maximum likelihood, and the Bayesian methods of inferring ancestral sequences and
      concludes that the Bayesian method, as implemented by MRBAYES 3.11, is preferred.
      Estimated ancestral sequences are of necessity the same length as the alignment
      on which the underlying phylogeny is based. A highly accurate method for
      correcting the estimated sequences is introduced, and it is shown that the
      correction permits inferring the sequences of ancient protein sequences with a
      very high degree of accuracy.

PMID- 16567643
TI  - Perceptual moments of conscious visual experience inferred from oscillatory brain
      activity.
AB  - Transient periods of synchronized oscillating neuronal discharges in the brain
      have been proposed to support the discrete perceptual moments underlying
      conscious visual experience. However, the information content of these perceptual
      moments remains a critical challenge to the understanding of consciousness. We
      uncovered this information content in four observers who consciously perceived
      each interpretation of the ambiguous Dali painting Slave Market with the
      Disappearing Bust of Voltaire. For each individual observer, we isolated the
      stimulus spatial frequency (SF) features underlying their overt judgments of the
      input as "the nuns" and "Voltaire". Every 2 ms between stimulus onset and overt
      response, we derived the sensitivity of the observer's oscillatory brain activity
      (in the theta, alpha, and beta bandwidths) to these SF features. Then, in each
      bandwidth, we estimated the moments (between stimulus onset and perceptual
      judgment) when perception-specific SF features were maximally integrated,
      corresponding to perceptual moments. We show that the centroparietal beta
      oscillations support perceptual moments underlying the conscious perception of
      the nuns, whereas theta oscillations support the perception of Voltaire. For both
      perceptions, we reveal the specific information content of these perceptual
      moments.

PMID- 16567644
TI  - Gene expression patterns in human placenta.
AB  - The placenta is the principal metabolic, respiratory, excretory, and endocrine
      organ for the first 9 months of fetal life. Its role in fetal and maternal
      physiology is remarkably diverse. Because of the central role that the placenta
      has in fetal and maternal physiology and development, the possibility that
      variation in placental gene expression patterns might be linked to important
      abnormalities in maternal or fetal health, or even variations in later life,
      warrants investigation. As an initial step, we used DNA microarrays to analyze
      gene expression patterns in 72 samples of amnion, chorion, umbilical cord, and
      sections of villus parenchyma from 19 human placentas from successful full-term
      pregnancies. The umbilical cord, chorion, amnion, and villus parenchyma samples
      were readily distinguished by differences in their global gene-expression
      patterns, many of which seemed to be related to physiology and histology.
      Differentially expressed genes have roles that include placental trophoblast
      secretion, signal transduction, metabolism, immune regulation, cell adhesion, and
      structure. We found interindividual differences in expression patterns in villus
      parenchyma and systematic differences between the maternal, fetal, and
      intermediate layers. A group of genes that was expressed in both the maternal and
      fetal villus parenchyma sections of placenta included genes that may be
      associated with preeclampsia. We identified sets of genes whose expression in
      placenta was significantly correlated with the sex of the fetus. This study
      provides a rich and diverse picture of the molecular variation in the placenta
      from healthy pregnancies.

PMID- 16567645
TI  - Neutral and adaptive variation in gene expression.
AB  - Variation among populations in gene expression should be related to the
      accumulation of random-neutral changes and evolution by natural selection. The
      following evolutionary analysis has general applicability to biological and
      medical science because it accounts for genetic relatedness and identifies
      patterns of expression variation that are affected by natural selection. To
      identify genes evolving by natural selection, we allocate the maximum among
      population variation to genetic distance and then examine the remaining variation
      relative to a hypothesized important ecological parameter (temperature). These
      analyses measure the expression of metabolic genes in common-gardened populations
      of the fish Fundulus heteroclitus whose habitat is distributed along a steep
      thermal gradient. Although much of the variation in gene expression fits a null
      model of neutral drift, the variation in expression for 22% of the genes that
      regress with habitat temperature was far greater than could be accounted for by
      genetic distance alone. The most parsimonious explanation for among-population
      variation for these genes is evolution by natural selection. In addition, many
      metabolic genes have patterns of variation incongruent with neutral evolution:
      They have too much or too little variation. These patterns of biological
      variation in expression may reflect important physiological or ecological
      functions.

PMID- 16567646
TI  - Solution structure of the N-domain of Wilson disease protein: distinct nucleotide
      binding environment and effects of disease mutations.
AB  - Wilson disease protein (ATP7B) is a copper-transporting P(1B)-type ATPase that
      regulates copper homeostasis and biosynthesis of copper-containing enzymes in
      human tissues. Inactivation of ATP7B or related ATP7A leads to severe
      neurodegenerative disorders, whereas their overexpression contributes to cancer
      cell resistance to chemotherapeutics. Copper-transporting ATPases differ from
      other P-type ATPases in their topology and the sequence of their nucleotide
      binding domain (N-domain). To gain insight into the structural basis of ATP7B
      function, we have solved the structure of the ATP7B N-domain in the presence of
      ATP by using heteronuclear multidimensional NMR spectroscopy. The N-domain
      consists of a six-stranded beta-sheet with two adjacent alpha-helical hairpins
      and, unexpectedly, shows higher similarity to the bacterial K(+)-transporting
      ATPase KdpB than to the mammalian Ca(2+)-ATPase or Na(+),K(+)-ATPase. The common
      core structure of P-type ATPases is retained in the 3D fold of the N-domain;
      however, the nucleotide coordination environment of ATP7B within this fold is
      different. The residues H1069, G1099, G1101, I1102, G1149, and N1150 conserved in
      the P(1B)-ATPase subfamily contribute to ATP binding. Analysis of the frequent
      disease mutation H1069Q demonstrates that this mutation does not significantly
      affect the structure of the N-domain but prevents tight binding of ATP. The
      structure of the N-domain accounts for the disruptive effects of >30 known Wilson
      disease mutations. The unique features of the N-domain provide a structural basis
      for the development of specific inhibitors and regulators of ATP7B.

PMID- 16567647
TI  - PR130 is a modulator of the Wnt-signaling cascade that counters repression of the
      antagonist Naked cuticle.
AB  - The Wnt-signaling cascade is required for several crucial steps during early
      embryogenesis, and its activity is modulated by various agonists and antagonists
      to provide spatiotemporal-specific signaling. Naked cuticle is a Wnt antagonist
      that itself is induced by Wnt signaling to keep Wnt signaling in check. Little is
      known about the regulation of this antagonist. We have recently shown that the
      protein phosphatase 2A regulatory subunit PR72 is required for the inhibitory
      effect of Naked cuticle on Wnt signaling. In the present study, we show that
      PR130, which has an N terminus that differs from that of PR72 but shares the same
      C terminus, also interacts with Naked cuticle but instead functions as an
      activator of the Wnt-signaling pathway, both in cell culture and during
      development. We find that PR130 modulates Wnt signal transduction by restricting
      the ability of Naked cuticle to function as a Wnt inhibitor. Our data establish
      PR130 as a modulator of the Wnt-signaling pathway and suggest a mechanism of Wnt
      signal regulation in which the inhibitory activity of Naked cuticle is determined
      by the relative level of expression of two transcripts of the same protein
      phosphatase 2A regulatory subunit.

PMID- 16567648
TI  - Approaches for biological and biomimetic energy conversion.
AB  - This article highlights areas of research at the interface of nanotechnology, the
      physical sciences, and biology that are related to energy conversion:
      specifically, those related to photovoltaic applications. Although much ongoing
      work is seeking to understand basic processes of photosynthesis and chemical
      conversion, such as light harvesting, electron transfer, and ion transport,
      application of this knowledge to the development of fully synthetic and/or hybrid
      devices is still in its infancy. To develop systems that produce energy in an
      efficient manner, it is important both to understand the biological mechanisms of
      energy flow for optimization of primary structure and to appreciate the roles of
      architecture and assembly. Whether devices are completely synthetic and mimic
      biological processes or devices use natural biomolecules, much of the research
      for future power systems will happen at the intersection of disciplines.

PMID- 16567649
TI  - New primate genus from the Miocene of Argentina.
AB  - Killikaike blakei is a new genus and species of anthropoid from the late Early
      Miocene of southeastern Argentina based on the most pristine fossil platyrrhine
      skull and dentition known so far. It is part of the New World platyrrhine clade
      (Family Cebidae; Subfamily Cebinae) including modern squirrel (Saimiri) and
      capuchin monkeys (Cebus) and their fossil relatives known from Early to Middle
      Miocene and subrecent periods. Living cebines are relatively large-brained,
      adroit predatory foragers and live within complex social groups, and wild
      capuchins exhibit a wide range of behaviors associated with enhanced
      intelligence. We show that K. blakei lacks diagnostic derived characteristics of
      the lower face and premolar dentition that are shared by modern cebines, but its
      strongly vaulted frontal bone and capacious anterior cranial fossa indicate the
      early evolution of an enlarged forebrain.

PMID- 16567650
TI  - How TRIM5alpha defends against retroviral invasions.

PMID- 16567651
TI  - Integrin-driven actin polymerization consolidates long-term potentiation.
AB  - Long-term potentiation (LTP), like memory, becomes progressively more resistant
      to disruption with time after its formation. Here we show that threshold
      conditions for inducing LTP cause a rapid, long-lasting increase in polymerized
      filamentous actin in dendritic spines of adult hippocampus. Two independent
      manipulations that reverse LTP disrupted this effect when applied shortly after
      induction but not 30 min later. Function-blocking antibodies to beta1 family
      integrins selectively eliminated both actin polymerization and stabilization of
      LTP. We propose that the initial stages of consolidation involve integrin-driven
      events common to cells engaged in activities that require rapid morphological
      changes.

PMID- 16567653
TI  - You can't always get what you want: conservation planning with feedback effects.

PMID- 16567652
TI  - mTOR is out of control in polycystic kidney disease.

PMID- 16567654
TI  - A functional AMPA receptor-calcium channel complex in the postsynaptic membrane.
AB  - Ca(2+) channels play critical roles in the regulation of synaptic activity. In
      contrast to the well established function of voltage-activated Ca(2+) channels in
      the presynaptic membrane for neurotransmitter release, some studies are just
      beginning to elucidate the functions of the Ca(2+) channels in the postsynaptic
      membrane. In this study, we demonstrated the functional association of alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors with the neuronal
      Ca(2+) channels. A series of biochemical studies showed the specific association
      of Ca(v)2.1 (alpha(1A)-class) and Ca(v)2.2 (alpha(1B)-class) with AMPA receptors
      in the postsynaptic membrane. Our electrophysiological and Ca(2+) imaging
      analyses of recombinant Ca(v)2.1 and AMPA receptors also showed functional
      coupling of the two channels. Considering the critical roles of postsynaptic
      intracellular concentration of Ca(2+) ([Ca(2+)](i)) increase and AMPA receptor
      trafficking for long-term potentiation (LTP) and long-term depression (LTD), the
      functional association of Ca(2+) channels with the AMPA receptors may provide new
      insights into the mechanism of synaptic plasticity.

PMID- 16567655
TI  - Folding-based molecular simulations reveal mechanisms of the rotary motor F1
      ATPase.
AB  - Biomolecular machines fulfill their function through large conformational changes
      that typically occur on the millisecond time scale or longer. Conventional
      atomistic simulations can only reach microseconds at the moment. Here, extending
      the minimalist model developed for protein folding, we propose the "switching Go
      model" and use it to simulate the rotary motion of ATP-driven molecular motor
      F(1)-ATPase. The simulation recovers the unidirectional 120 degrees rotation of
      the gamma-subunit, the rotor. The rotation was induced solely by steric repulsion
      from the alpha(3)beta(3) subunits, the stator, which undergoes conformation
      changes during ATP hydrolysis. In silico alanine mutagenesis further elucidated
      which residues play specific roles in the rotation. Finally, regarding the
      mechanochemical coupling scheme, we found that the tri-site model does not lead
      to successful rotation but that the always-bi-site model produces approximately
      30 degrees and approximately 90 degrees substeps, perfectly in accord with
      experiments. In the always-bi-site model, the number of sites occupied by
      nucleotides is always two during the hydrolysis cycle. This study opens up an
      avenue of simulating functional dynamics of huge biomolecules that occur on the
      millisecond time scales involving large-amplitude conformational change.

PMID- 16567656
TI  - Life stress and diminished expression of genes encoding glucocorticoid receptor
      and beta2-adrenergic receptor in children with asthma.
AB  - Despite evidence that stressful experience can exacerbate the symptoms of asthma,
      little is known about the biological mechanisms through which this occurs. This
      study examined whether life stress reduces expression of the genes coding for the
      glucocorticoid receptor and the beta(2)-adrenergic receptor. A total of 77
      children were enrolled in the study (59% male; mean age, 13.5 years). Thirty-nine
      of them were physician-diagnosed with asthma, and 38 were healthy. After an in
      depth interview regarding stressful experiences, leukocytes were collected
      through antecubital venipuncture, and real-time RT-PCR was used to quantify mRNA.
      Chronic stress was associated with reduced expression of mRNA for the beta(2)
      adrenergic receptor among children with asthma. In the sample of healthy
      children, however, the direction of this effect was reversed. The occurrence of a
      major life event in the 6 months before the study was not sufficient to influence
      patterns of gene expression. When such events occurred in the context of a
      chronic stressor, however, their association with patterns of gene expression was
      accentuated. Children with asthma who simultaneously experienced acute and
      chronic stress exhibited a 5.5-fold reduction in glucocorticoid receptor mRNA and
      a 9.5-fold reduction in beta(2)-adrenergic receptor mRNA relative to children
      with asthma without comparable stressor exposure. These findings suggest that
      stressful experience diminishes expression of the glucocorticoid and beta(2)
      adrenergic receptor genes in children with asthma. To the extent that it
      diminishes sensitivity to the antiinflammatory properties of glucocorticoids or
      the bronchodilatory properties of beta-agonists, this process could explain the
      increased asthma morbidity associated with stress.

PMID- 16567657
TI  - Simulation of polymer translocation through protein channels.
AB  - A modeling algorithm is presented to compute simultaneously polymer conformations
      and ionic current, as single polymer molecules undergo translocation through
      protein channels. The method is based on a combination of Langevin dynamics for
      coarse-grained models of polymers and the Poisson-Nernst-Planck formalism for
      ionic current. For the illustrative example of ssDNA passing through the alpha
      hemolysin pore, vivid details of conformational fluctuations of the polymer
      inside the vestibule and beta-barrel compartments of the protein pore, and their
      consequent effects on the translocation time and extent of blocked ionic current
      are presented. In addition to yielding insights into several experimentally
      reported puzzles, our simulations offer experimental strategies to sequence
      polymers more efficiently.

PMID- 16567658
TI  - The evolution of viral emergence.

PMID- 16567659
TI  - Legume flowers bear fruit.

PMID- 16567660
TI  - Finding the final pieces of the vitamin B12 biosynthetic jigsaw.

PMID- 16567662
TI  - Has stroke shifted from hemorrhagic to ischemic in China?

PMID- 16567663
TI  - Referral bias may underestimate number of very elderly patients eligible for
      rtPA.

PMID- 16567664
TI  - Economic benefit of increasing utilization of intravenous tissue plasminogen
      activator for acute ischemic stroke in the United States.

PMID- 16567665
TI  - Hyperglycemia and hyperinsulinemia in circulatory disorder after subarachnoid
      hemorrhage.

PMID- 16567666
TI  - The EMMY trial of uterine artery embolization for the treatment of symptomatic
      uterine fibroid tumors: randomized, yes, but a flawed trial nonetheless.

PMID- 16567667
TI  - Reporting standards for endovascular treatment of lower extremity deep vein
      thrombosis.

PMID- 16567668
TI  - Quality improvement guidelines for the treatment of lower extremity deep vein
      thrombosis with use of endovascular thrombus removal.

PMID- 16567669
TI  - Guidelines for the use of retrievable and convertible vena cava filters: report
      from the Society of Interventional Radiology multidisciplinary consensus
      conference.

PMID- 16567670
TI  - Nonhepatic arteries originating from the hepatic arteries: angiographic analysis
      in 250 patients.
AB  - PURPOSE: To investigate the prevalence and patterns of origin of nonhepatic
      arteries originating from the proper hepatic artery (PHA) or its distal branches
      and to assess their relation to anatomic variations. MATERIALS AND METHODS:
      Digital subtraction celiac arteriography and selective left hepatic arteriography
      was performed in 250 patients with hepatocellular carcinoma. Three interventional
      radiologists interpreted the angiograms on the monitor by consensus. If
      necessary, further superselective arteriography was performed. The prevalence of
      nonhepatic arteries, their sites of origin, and the influence of underlying
      anatomic variants were analyzed. RESULTS: Nonhepatic arteries were found in 205
      patients. The most common nonhepatic artery was the right gastric artery (RGA; n
      = 196), followed by the hepatic falciform artery (HFA; n = 129), accessory left
      gastric artery (LGA; n = 43), posterior superior pancreaticoduodenal artery
      (PSPDA; n = 18), and left inferior phrenic artery (LIPA; n = 5). The left hepatic
      artery (LHA) was the most frequent origin of nonhepatic arteries (170 of 250).
      Regardless of anatomic variation, the most common origins of the RGA and HFA were
      the PHA and the segment IV hepatic artery, respectively. In patients with an
      aberrant LHA from the LGA, no accessory LGAs or LIPAs were found. PSPDAs
      preferentially arose from variant hepatic arteries arising from the
      gastroduodenal artery. CONCLUSIONS: Nonhepatic arteries commonly arise from the
      hepatic arteries, especially the LHA and PHA. Moreover, variants of the celiac
      and hepatic arteries influence the prevalence and sites of origin of nonhepatic
      arteries.

PMID- 16567671
TI  - Uterine artery embolization in the treatment of symptomatic uterine fibroid
      tumors (EMMY trial): periprocedural results and complications.
AB  - PURPOSE: Uterine artery embolization (UAE) is an emerging treatment for
      symptomatic uterine fibroid tumors. This study was performed to evaluate the
      periprocedural results of the UAE procedure and identify risk factors for
      technical failure, fever after UAE, pain, and other complications. MATERIALS AND
      METHODS: As part of a multicenter, randomized trial to compare UAE versus
      hysterectomy in patients with symptomatic uterine fibroid tumors, 81 patients
      underwent UAE. Univariate and multivariate analyses were used to identify
      predictors for technical failure, postprocedural fever, complications as defined
      by the Society of Interventional Radiology (SIR), and pain scores. RESULTS: The
      technical failure rate according to SIR guidelines was 5.3% (95% CI, 2.3%-10.1%).
      The procedural failure rate was 17.3% (95% CI, 9.8%-27.3%). Bilateral failure
      occurred in four of 81 patients and unilateral failure occurred in 10 of 81
      patients. Technical failure occurred mainly as a result of difficult anatomy
      (3.7%) or absence of the uterine artery (3.1%). The overall complication rates
      were 28.4% during the patients' hospital stay and 60.5% for the 6 weeks after
      discharge. The risk of technical failure was found to increase in the presence of
      a single fibroid tumor (odds ratio [OR], 6.21; 95% CI, 1.65-23.41; P = .007)
      and/or a small uterine volume (<500 cm(3); OR, 10.8; 95% CI, 1.25-93.36; P =
      .03). The amount of embolization material was associated with the onset of fever
      after UAE (OR, 2.05; 95% CI, 1.09-3.87; P = .027), major complications (OR, 5.68;
      95% CI, 2.05-15.75; P = .001), and high pain scores (OR, 1.97; 95% CI, 1.08-3.58;
      P = .027). CONCLUSIONS: The procedural failure rate for UAE was higher than those
      reported by others, mainly as a result of difficult anatomy and absence of a
      uterine artery in some cases. The risk of procedural failure was increased for
      patients with single fibroid tumors and/or small uterine volumes. A clear dose
      effect response was revealed between the amount of embolization material used and
      the risk for postprocedural fever, major complications, and severe pain.

PMID- 16567672
TI  - Endovascular embolization of symptomatic arteriovenous fistulas secondary to
      lower-limb in situ venous bypass grafts.
AB  - PURPOSE: To evaluate the safety and efficacy of endovascular treatment of
      symptomatic arteriovenous (AV) fistulas associated with femoropopliteal in situ
      venous bypass grafts. MATERIALS AND METHODS: Twenty-one patients underwent
      embolization of symptomatic AV fistulas associated with lower-limb bypass with
      use of the saphenous vein (n = 16) or femoral vein (n = 5). The procedures were
      performed with microcatheters and metallic coils. Indications for embolization
      were venous congestion (n = 15) and arterial insufficiency (n = 6). Eight
      patients had persistent lower-limb edema, seven had painful inflammatory skin
      thickening, three had intermittent claudication, and three had nonhealing ulcers.
      RESULTS: Forty-four AV fistulas were embolized. Symptoms of venous congestion
      regressed completely in 12 of 15 patients (80%). Partial symptom improvement was
      achieved in three other patients (20%), two of whom had persistent lower-limb
      edema and bypass with use of the femoral vein. Five of six patients with ischemic
      symptoms (83%) had complete symptom relief. One patient (17%) whose ischemic
      ulcer did not recover despite successful embolization of AV fistulas required an
      amputation 4 months later. Overall, 17 of 21 patients (81%) showed complete
      recovery of clinical symptoms. There was no bypass occlusion during follow-up
      (mean, 17.5 months; range, 1-45 months). CONCLUSIONS: Embolization of symptomatic
      AV fistulas secondary to lower-limb in situ venous bypass is a safe and efficient
      alternative to surgical ligature. Complete regression of clinical symptoms is
      less likely when the bypass is performed with use of the femoral vein.

PMID- 16567673
TI  - Mechanical thrombectomy of acute iliofemoral deep vein thrombosis with use of an
      Arrow-Trerotola percutaneous thrombectomy device.
AB  - PURPOSE: To evaluate the immediate and 1-year clinical outcomes of mechanical
      thrombectomy with use of the Arrow-Trerotola percutaneous thrombectomy device
      (PTD) with or without low-dose urokinase in the treatment of acute iliofemoral
      deep vein thrombosis (DVT). MATERIALS AND METHODS: Mechanical thrombectomy with
      the PTD was performed in 25 patients with acute iliofemoral DVT. Thrombolytic
      therapy with low-dose urokinase was used in all patients without
      contraindications (n = 20). Other therapies used in combination included inferior
      vena cava filter insertion (n = 5), sheath aspiration thrombectomy (n = 25), and
      angioplasty and stent placement (n = 20). RESULTS: Initial technical and clinical
      success was achieved in all cases. In the 20 patients who had no
      contraindications to the use of urokinase, the dosage of urokinase did not exceed
      1 million IU (range, 360,000-1,000,000 IU; mean, 640,000 IU). The mean time of
      urokinase infusion was 16 hours (range, 12-20). In five patients who had a
      contraindication to the use of urokinase, mechanical thrombectomy with the PTD
      was successful without the use of urokinase. There were no major complications.
      Primary patency of the stent-implanted common iliac vein segment was achieved at
      1 year in 17 of 20 patients (85%). The overall 1-year clinical success rate was
      92% (23 of 25 patients). Valvular insufficiency occurred in two patients (8%).
      CONCLUSION: The PTD is an effective mechanical thrombectomy device in the
      treatment of acute iliofemoral DVT with or without adjunctive urokinase
      thrombolysis.

PMID- 16567674
TI  - Efficacy and safety results with the LifeSite hemodialysis access system versus
      the Tesio-Cath hemodialysis catheter at 12 months.
AB  - PURPOSE: To compare the performance and safety of a fully subcutaneous vascular
      access device, the LifeSite hemodialysis access system, versus a tunneled
      hemodialysis catheter, the Tesio-Cath, at 1 year after implantation. MATERIALS
      AND METHODS: Sixty-eight patients who required hemodialysis received implantation
      of the LifeSite device or a Tesio-Cath device as a part of this multicenter
      study. Thirty-four patients were treated in each group. The endpoints observed
      included blood flow rates and associated venous pressures, overall and device
      related adverse events, the need for thrombolytic infusions, device-related
      infections (DRIs) and associated hospitalizations, and technical device survival.
      RESULTS: During the 12-month observation period, significantly higher venous
      pressures were required in patients with the Tesio-Cath to achieve blood flow
      rates comparable with those achieved with the LifeSite device. Patients in the
      LifeSite group experienced a significantly lower rate of non-device-related
      adverse events (P < .001), device-related adverse events (P < .016), need for
      thrombolytic infusions (P < .002), and DRIs (P < .013) compared with patients in
      the Tesio-Cath group. There was a trend toward a lower number of hospital days
      per month for DRIs in the LifeSite group, with the rate for the Tesio-Cath group
      being twice that in the LifeSite group. The use of the LifeSite device was also
      associated with a significantly higher probability of device survival for 12
      months after censoring for planned removals (P < .031). CONCLUSIONS: The results
      of the present study demonstrate superior device performance and technical device
      survival, reduced complications, and the need for fewer interventions with the
      LifeSite hemodialysis access system compared with a standard hemodialysis
      catheter during a 1-year time period after implantation.

PMID- 16567675
TI  - The role of functional MR imaging in the assessment of tumor response after
      chemoembolization in patients with hepatocellular carcinoma.
AB  - PURPOSE: To assess treatment response of hepatocellular carcinoma (HCC) after
      transarterial chemoembolization (TACE) with use of diffusion and dynamic contrast
      medium-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: MR
      imaging studies before and after TACE in 38 patients with HCC (33 male patients
      and five female patients) were evaluated. Diffusion and dynamic contrast medium
      enhanced MR imaging was performed on a 1.5-T unit. The imaging protocol included
      T2-weighted fast spin-echo, breath-hold diffusion-weighted echoplanar, and breath
      hold unenhanced and contrast medium-enhanced T1-weighted three-dimensional fat
      saturation gradient-recalled echo imaging in the arterial and portal venous
      phases. Tumor size, percent enhancement, and apparent diffusion coefficient (ADC)
      values were recorded before and after treatment. Survival analysis was also
      performed. RESULTS: The study included 38 lesions with a mean diameter of 8.0 cm.
      Mean reduction in tumor diameter was 8 mm after treatment (t test; P = .0005),
      which did not fulfill Response Evaluation Criteria in Solid Tumors for complete
      or partial response. Reduction in tumor enhancement in the arterial (30%) and
      venous (47%) phases was statistically significant (signed-rank test; P = .0003
      and P < 0.00005, respectively). Tumor ADC value increased from 0.0015 mm(2)/sec
      to 0.0018 mm(2)/sec after treatment (t test; P = .026), whereas the ADC values
      for the liver, spleen, and muscle remained unchanged. Median patient survival was
      19 months. CONCLUSIONS: After TACE, tumors demonstrated decreased size and
      enhancement with increases in ADC values. In this cohort, diffusion and dynamic
      contrast medium-enhanced MR imaging parameters were significantly altered after
      TACE, and these could be useful tools in the assessment of tumor response.

PMID- 16567676
TI  - Radiofrequency ablation of small renal cell carcinomas using multitined
      expandable electrodes: preliminary experience.
AB  - PURPOSE: Radiofrequency ablation is a minimally invasive, nephron-sparing option
      for renal cell carcinoma (RCC) in poor surgical candidates. We report our
      contemporary experience with RCC radiofrequency ablation using multitined
      expandable electrodes along with an aggressive treatment strategy to displace
      adjacent viscera away from probe tines. Involution of the treatment zone was
      assessed over time. MATERIALS AND METHODS: Over a 36-month period, a quality
      assurance database identified 22 patients with 26 sporadic RCC who underwent 43
      ablations during 27 radiofrequency ablation sessions. The mean age of the cohort
      was 71 years (range, 47-89 y). Mean RCC diameter was 2.2 cm (range, 1-4 cm).
      Twenty-six of radiofrequency ablation sessions were performed using multitined
      expandable electrodes. All ablations used CT guidance with moderate sedation.
      Adjunctive techniques used during ablation were recorded, as were instances in
      which ablation mandated penetration of tines beyond the kidney margin. Post
      treatment ablation zones were measured from CT/MR images to evaluate serial
      involution and treatment response. RESULTS: Technical success in targeting and
      ablation was 100%. Follow-up periods ranged from 1 to 31 months (mean, 11.2).
      During this period, one patient presented with marginal local recurrence and
      underwent repeat radiofrequency ablation. Adjunctive techniques in four patients
      included water injection for displacement of the tail of the pancreas (n = 1) or
      descending colon (n = 3). Deliberate penetration of tines beyond the margins of
      the kidney was performed in 41% of cases; no hemorrhage occurred in these cases.
      No major complications occurred. Minor complications occurred in 17% of patients,
      including asymptomatic pneumothorax, perirenal hematomas, subcutaneous hematoma,
      and subcutaneous abscess. After 6 months, mean involution of the ablation zone
      was 15% from baseline volume per year. CONCLUSION: Multitined expandable
      radiofrequency electrodes produce a high rate of local control for small RCCs
      with a low complication rate, even when tine penetration of the kidney is
      required for an adequate tumor treatment margin. Adjacent organs can be protected
      with adjunctive percutaneous maneuvers.

PMID- 16567677
TI  - Intervascular anastomoses created by an endovascular approach: technical aspects
      and initial results in an animal study.
AB  - PURPOSE: The current article describes the initial results after the creation of
      intervascular connections with use of an exclusively endovascular approach.
      Connections of two vessels were performed in the thoracic and abdominal areas
      with use of a kinematic needle without traversing a solid organ. The materials
      developed specifically for this technique are described. MATERIALS AND METHODS:
      The procedure was carried out in 11 animals and consisted of bringing together
      two vascular structures with use of magnets, performing a puncture from the lumen
      of one vessel to that of the other, and inserting a prosthesis between the two.
      The prosthesis has a biconical morphology and is made with a 0.016-inch
      monofilament of nitinol. Its most outstanding feature is that, when it is dilated
      with a balloon, it shortens and "rolls up," flattening its ends. This allows good
      fixation to the vessel wall, avoiding the protrusion of metal into the lumen of
      the native vessel. RESULTS: On four occasions, the aorta was connected to another
      nearby vessel: the abdominal aorta to the inferior vena cava (IVC; n = 1), the
      ascending aorta to the trunk of the pulmonary artery (n = 1), and the descending
      aorta to the left pulmonary artery (n = 2). On another four occasions, two veins
      were connected: the portal vein and the IVC. Finally, on three occasions, the
      right pulmonary artery was connected to the superior vena cava. The connection
      was safely and accurately performed with passage of a guide wire in all cases. In
      two experiments, the prosthesis was too short and leakage with massive bleeding
      was observed after a successful initial deployment of the prosthesis CONCLUSION:
      Intervascular anastomoses created by an endovascular approach are feasible in the
      authors' experimental model for several different vessel pairings.

PMID- 16567678
TI  - Pluronic F127: application in arterial embolization.
AB  - PURPOSE: Pluronic is a substance that is widely used in medical and
      pharmaceutical fields. In particular, 20% Pluronic F127 solution is a unique
      substance that is liquid at less than 15 degrees C and gelatinous at 25 to 60
      degrees C. In this study, the authors took advantage of the gelation property of
      Pluronic F127 at human body temperature to simulate embolization and dissolution
      of the embolism in the renal artery and the superior mesenteric artery (SMA)
      using a rabbit model. MATERIALS AND METHODS: Four female Japanese rabbits
      (weight, 2.5-3 kg each) were used. The renal artery was fitted with a 4-F cobra
      type catheter and embolized with a 20% Pluronic F127 solution at a temperature of
      20 degrees C. The embolic effect was evaluated by angiography immediately after
      the initial injection and every 15 minutes for 2.5 hours after embolization.
      After 24 hours, pathologic changes of the renal parenchyma were also evaluated.
      The embolic effect for SMA and ischemic changes of the intestine were evaluated
      in the same manner. RESULTS: Angiographic findings showed that Pluronic F127
      caused embolization immediately after injection and dissolved in the renal artery
      and the SMA after 90 to 120 minutes. The pathologic findings showed no ischemic
      change in the renal parenchyma. Necrosis was not found in the intestine, but
      focal hemorrhagic changes were extensively present when the gel had dissolved.
      This suggested that Pluronic F127 dissolved before severe tissue damage could
      occur. CONCLUSION: Pluronic F127 can potentially be used as a temporary embolic
      material.

PMID- 16567679
TI  - Radiofrequency ablation of the liver in a rabbit model: creation of artificial
      ascites to minimize collateral thermal injury to the diaphragm and stomach.
AB  - PURPOSE: To assess whether the creation of artificial ascites during
      radiofrequency (RF) ablation of the subcapsular portion of the liver can minimize
      collateral thermal injury to the diaphragm and stomach. MATERIALS AND METHODS: A
      total of 20 percutaneous RF ablation procedures were performed in the livers of
      10 rabbits (control, n = 5; experimental, n = 5) with use of an internally cooled
      electrode (1-cm active tip). In the experimental group, artificial ascites was
      established before RF ablation by dripping 320 mL of normal saline solution via a
      20-gauge sheathed needle to separate the liver from the diaphragm and stomach. In
      each rabbit, two subcapsular ablation zones were made in the inferior tip of the
      left lobe of the liver adjacent to the stomach and in the far dome of the right
      lobe next to the diaphragm consecutively. After the animals were killed 3 days
      after the procedure, the frequency, size, and degree of thermal injury were
      compared between the experimental and control groups. The degree of thermal
      injury was graded by visual inspection according to a four-point scoring system.
      Representative cases underwent gross and histologic analysis. RESULTS: Artificial
      ascites was achieved successfully with a single puncture in all rabbits in the
      experimental group. Mean procedure time for the formation of artificial ascites
      was 9 minutes. There was no difference in the size of the RF ablation zones in
      the liver between the two groups (P > .05). Thermal injury in the adjacent organs
      was observed significantly more frequently in the control group compared with the
      experimental group (diaphragm, 100% vs 0; stomach, 80% vs 20%; P < .05).
      CONCLUSION: Creation of artificial ascites may be a simple and useful technique
      that can be used to reduce the frequency and severity of thermal injury during RF
      ablation of subcapsular hepatic tumors.

PMID- 16567680
TI  - Radiofrequency renal ablation: in vivo comparison of internally cooled,
      multitined expandable and internally cooled perfusion electrodes.
AB  - PURPOSE: To evaluate the in vivo efficiency of radiofrequency ablation using an
      internally cooled-perfusion (ICP) electrode for inducing coagulation necrosis
      compared with those of RFA using internally cooled or multitined expandable
      electrodes in porcine kidneys. MATERIALS AND METHODS: Using a 200 W generator and
      internally cooled and ICP electrodes or a 150 W generator and a multitined
      expandable electrode, a total of 15 radiofrequency ablations were performed in
      the kidneys of nine pigs. After placement of an electrode in the lower pole of a
      kidney, one ablation zone was created using one of three different regimens:
      group A, radiofrequency ablation using an internally cooled electrode; group B,
      radiofrequency ablation using an ICP electrode with 14.6% NaCl solution
      instillation at 1 mL/minute; group C, radiofrequency ablation using a multitined
      expandable electrode. Three days after the procedures, contrast-enhanced CT scans
      were obtained to evaluate ablation region volumes, and kidneys were harvested for
      gross measurements. The three groups were compared with respect to technical
      parameters such as changes in impedance and current during radiofrequency
      ablation. The dimensions of thermal ablation zones created in the three groups
      were compared histologically. RESULTS: In vivo study showed that ICP electrode
      allowed a greater energy delivery than internally cooled or multitined expandable
      electrode during radiofrequency ablation: 63.3 +/- 8.8 kJ in group A; 101 +/- 3.3
      kJ in group B; and 61.8 +/- 12.5 kJ (P < .05). In vivo studies showed
      radiofrequency ablation using ICP electrode achieved larger mean coagulation
      volumes than radiofrequency ablation using the other electrodes: 12.0 +/- 3.9
      cm(3) in group A; 30.5 +/- 7.6 cm(3) in group B; and 11.6 +/- 6.7 cm(3) in group
      C (P < .05). In addition, group B had a larger mean short-axis diameter of
      radiofrequency-induced coagulation necrosis than groups A or C: 2.6 +/- 0.5 cm in
      group A; 3.6 +/- 0.4 cm in group B; and 2.4 +/- 0.7 cm in group C (difference
      between groups B and C: P < .05). CONCLUSIONS: Radiofrequency ablation using an
      ICP electrode showed better performance at creating coagulation necrosis than
      radiofrequency ablation using internally cooled or multitined expandable
      electrodes in this porcine renal model.

PMID- 16567681
TI  - Translumbar repair of a type II endoleak associated with an aorta-to-left renal
      vein fistula after aortic stent-graft placement.
AB  - An abdominal aortic aneurysm (AAA) is a serious medical condition with
      significant associated morbidity and mortality. Endograft repair of AAAs is a
      therapy in evolution, but offers promise as a minimally invasive treatment
      option. Persistent sac pressurization via endoleaks has limited wider application
      of stent-grafting technology. The present report describes a case of an AAA with
      rupture into a retroaortic left renal vein that was treated acutely with aortic
      stent-graft repair. Continued aneurysm enlargement and a large type II endoleak
      drained by an arteriovenous fistula were subsequently treated via a translumbar
      approach.

PMID- 16567682
TI  - Endovascular repair of a bleeding secondary aortoenteric fistula with acute leg
      ischemia: a case report and review of the literature.
AB  - The endovascular approach seems very attractive for patients with bleeding
      secondary aortoenteric fistulas (SAEF) and limb ischemia, particularly when there
      is no associated sepsis. Aortic stent-grafting can rapidly seal the aortoenteric
      communication and ensure limb reperfusion. In the present case, a 53-year-old man
      with a bleeding SAEF and acute leg ischemia underwent aortic stent-grafting. Ten
      months later, CT and leukocyte scan (Tc-99m) showed no evidence of graft
      infection and the patient remains well 18 months postoperatively. In the typical
      patient with a bleeding SAEF, endoluminal treatment, if feasible anatomically,
      should be considered as first-choice treatment whether it represents a "bridging"
      step or a "definite" solution.

PMID- 16567683
TI  - Successful transfemoral creation of an intrahepatic portosystemic shunt with use
      of the Viatorr device.
AB  - Although the large majority of cases are anatomically favorable and therefore
      technically feasible, congenital or acquired conditions may complicate or even
      preclude successful creation of a transjugular intrahepatic portosystemic shunt
      (TIPS). The present report describes the use of the inferior right hepatic vein
      from a femoral vein access to obtain portal access and place a covered stent,
      reconstruct a partially occluded portal vein, and embolize large gastric varices
      in a patient with a persistent left superior vena cava (SVC) and absent right
      SVC.

PMID- 16567684
TI  - Malignant hypertension during cryoablation of an adrenal gland tumor.
AB  - The authors report a case of hypertensive crisis during cryoablation of an
      adrenal metastasis. This case is of particular interest not only because of the
      nature of the complication but also because of the timing of the hypertensive
      crisis. Based on their observations, the authors suggest that it may be prudent
      to pretreat this patient population with alpha-adrenergic blocking medications
      (eg, phenoxybenzamine), as is typically done for patients with neuroendocrine
      tumors such as pheochromocytoma. Preemptive intervention with these medications
      requires close collaboration between radiology and anesthesia care teams.

PMID- 16567685
TI  - The positive effect of targeted marketing on an existing uterine fibroid
      embolization practice.
AB  - PURPOSE: Although uterine fibroid embolization is an effective treatment option
      for symptomatic women, it is unclear what methods can be used to expand referrals
      in an already established practice. The authors tested the hypothesis that an
      advertising strategy focused on a defined target market can expand an existing
      uterine fibroid embolization practice. MATERIALS AND METHODS: A market-driven
      planning sequence was employed. This included a determination of goals, an
      examination of current competition, determination of target market based on local
      environment and previous consumer use, pretest of product sample, and
      implementation of advertisement. Based on the analysis the authors determined
      that the target audience was professional black women aged 35 to 45. A specific
      weekly magazine was selected due to readership demographics. An advertisement was
      run for 8 consecutive weeks. The authors prospectively tracked patient inquiries,
      clinic visits, cases performed, and revenues generated for 3 months following the
      initial advertisement. All patients were seen in a fully staffed, preexisting
      fibroid clinic located within an urban, university-based academic practice
      performing 250 uterine fibroid embolizations annually. RESULTS: Ninety calls were
      received directly related to the advertisement. There were 35 clinic visits,
      which resulted in 17 uterine fibroid embolizations and 52 total MR imaging
      procedures. Eighteen patients were not considered candidates based on established
      protocols. The 17 extra cases performed over 3 months represented a 27% increase
      in case volume. Total professional cash collections for these cases (including MR
      imaging) were 58,317 US dollars. The cost of advertising was 8,000 US dollars. As
      a result of existing infrastructure, no additional costs were necessary. This
      resulted in a net revenue gain 50,317 US dollars and a nonannualized rate of
      return of approximately 625%. CONCLUSION: As Interventional Radiologists look to
      develop and expand existing practices, traditional marketing tools such as those
      utilized in this study can be used to facilitate practice growth for specific
      clinical programs, such as uterine artery embolization. Defining a target market
      can significantly expand an existing uterine fibroid embolization practice. The
      optimal choice of targeted media awaits verification from future studies.

PMID- 16567686
TI  - Sloughing of intraductal tumor thrombus of hepatocellular carcinoma after
      transcatheter chemoembolization causing obstructive jaundice and acute
      pancreatitis.

PMID- 16567687
TI  - Treatment of carotid arteriovenous fistula with balloon-expandable
      tracheobronchial covered stent.

PMID- 16567688
TI  - Cephalosporin-induced myoclonus.

PMID- 16567689
TI  - Patient page. Can our leisure activities help to prevent cognitive decline?

PMID- 16567690
TI  - Clinical findings of the phakomatoses: neurofibromatosis.

PMID- 16567691
TI  - What does cerebral platelet activation mean in the setting of carotid stenosis?

PMID- 16567692
TI  - Cognitive leisure activities, but not watching TV, for future brain benefits.

PMID- 16567693
TI  - REM sleep behavior disorder: a possible early marker for synucleinopathies.

PMID- 16567695
TI  - Levels and value of platelet activity in patients with severe internal carotid
      artery stenosis.
AB  - BACKGROUND: Turbulent blood flow caused by arterial stenosis can induce platelet
      activation and aggregation, which subsequently participate in arterial
      thromboembolic events. OBJECTIVE: To test the hypothesis that platelet activation
      (expressed by CD62p) is enhanced in cerebral vs systemic circulation in patients
      with severe internal carotid artery (ICA) stenosis. METHODS: Platelet CD62p
      expression was prospectively measured using flow cytometry in 35 consecutive
      symptomatic patients with severe ICA stenosis and in 20 at-risk control subjects
      who underwent both coronary and cerebral angiographic studies due to angina
      pectoris and suspicious vertebral artery or intracranial artery stenosis. The
      CD62p expression was also evaluated in 20 healthy subjects. Blood samples were
      first drawn from the right internal jugular vein (cerebral circulation) and right
      femoral vein (systemic circulation) before extra- and intracerebral angiographic
      examination of both patients and at-risk control subjects and again at 40 minutes
      after ICA stenting. Clopidogrel was administered to the patients following the
      second blood sampling. RESULTS: Systemic CD62p expression was higher in patients
      than in both the healthy and at-risk control subjects (both p < 0.0001).
      Additionally, cerebral CD62p expression was higher in patients than in at-risk
      control subjects (p < 0.0001) prior to intervention. Moreover, CD62p expression
      was higher in cerebral circulation than in systemic circulation in the patients
      (p < 0.0001) before ICA stenting. However, CD62p expression was less enhanced in
      cerebral circulation than in systemic circulation after ICA stenting (p <
      0.0001). Furthermore, CD62p expression was decreased after 3 months of follow-up
      (p < 0.0001). CONCLUSIONS: Compared to systemic CD62p expression, cerebral CD62p
      expression was more enhanced prior to ICA stenting and was less enhanced after
      ICA stenting in patients with severe ICA stenosis.

PMID- 16567694
TI  - MRI of the brain and cervical spinal cord in rhizomelic chondrodysplasia
      punctata.
AB  - BACKGROUND: The classic rhizomelic chondrodysplasia punctata (RCDP) phenotype
      involves a typical facial appearance, cataracts, skeletal dysplasia causing
      disproportionate somatic growth failure, microcephaly, and severe psychomotor
      defects. Biochemical abnormalities include impaired plasmalogen biosynthesis in
      all forms of RCDP and accumulation of phytanic acid in RCDP type 1. A subset of
      patients has a milder clinical and biochemical phenotype, with less severe
      neurologic impairment and an incomplete deficiency in plasmalogens. The impact of
      plasmalogen deficiency on neurologic function is severe, causing spasticity and
      mental defects, but its pathomechanism is still unknown. The authors specifically
      focused on myelination because myelin is rich in ethanolamine plasmalogens.
      OBJECTIVE: To define the neuroimaging characteristics of the genetic peroxisomal
      disorder RCDP. METHODS: Twenty-one MR images of the brain and cervical spine of
      11 patients were evaluated and correlated with neurologic and biochemical
      profiles. RESULTS: No abnormalities on MRI were seen in the patients with a mild
      phenotype of RCDP, whereas delayed myelination, ventricular enlargement and
      increased subarachnoidal spaces, supratentorial myelin abnormalities, and
      cerebellar atrophy were observed in patients with the severe phenotype of both
      RCDP type 1 and 3. The severity of both the MRI abnormalities and the clinical
      phenotype is correlated with the plasmalogen level. CONCLUSIONS: The severe
      phenotype of rhizomelic chondrodysplasia punctata (RCDP) is accompanied by a
      specific pattern of both developmental and regressive MRI abnormalities.
      Plasmalogen levels seem to play an important role in the pathophysiology of CNS
      abnormalities in RCDP. Increased phytanic acid appears not to be the cause of
      cerebellar atrophy.

PMID- 16567696
TI  - Quality of hospital care in African American and white patients with ischemic
      stroke and TIA.
AB  - OBJECTIVE: To examine whether differences exist in the in-hospital diagnostic
      evaluation and treatment of African American and white patients with ischemic
      stroke (IS) and TIA. METHODS: The authors used a state-wide hospital-based stroke
      registry prototype designed to measure and track the quality of acute stroke
      care. Weighted descriptive statistics for each racial group are reported for the
      following variables, which were deemed to be potential confounders of the
      association between race and the quality of stroke care: age, gender, insurance
      status, emergency medical services arrival, functional status on presentation,
      modified Rankin score at discharge, stroke subtype, neurologist involved in care,
      and stroke pathway utilization. The magnitude and significance of the
      associations between race and each quality indicator of in-hospital acute stroke
      care were determined by separate multiple logistic regression models, adjusting
      for all potential confounding variables. RESULTS: Among patients admitted with IS
      and TIA who were alive at discharge (n = 1,837), 340 (18.5%) were African
      American and 1497 (81.5%) were white. After multivariate analysis, African
      Americans were less likely to have a door-to-CT time of less than 25 minutes
      (odds ratio [OR] 0.13 [CI 0.049 to 0.32]), obtain cardiac monitoring (OR 0.54 [CI
      0.29 to 1.03]), undergo dysphagia screening (OR 0.69 [CI 0.50 to 0.95]), and
      receive smoking cessation counseling (OR 0.27 [CI 0.17 to 0.42]). CONCLUSIONS:
      Quality of hospital care for African American and white patients with acute
      ischemic stroke and TIA was similar in many respects. However, African Americans
      were less likely to receive a CT within 25 minutes of arrival, cardiac
      monitoring, dysphagia screening, and smoking cessation counseling.

PMID- 16567697
TI  - Predictors for malignant middle cerebral artery infarctions: a postmortem
      analysis.
AB  - BACKGROUND: Early detection of malignant infarction of the middle cerebral artery
      (MI-MCA) is important because of possible treatment by hemicraniectomy.
      OBJECTIVE: To investigate the anatomic and vascular predictors of MI-MCA. METHOD:
      The authors evaluated 192 consecutive autopsies of patients with nonlacunar
      cerebral infarction affecting the MCA territory. MI-MCA was defined by an infarct
      with temporal or central brain herniation and brain swelling. The autopsy
      protocol included a systematic analysis of intracranial arteries (including the
      bony segments of carotid and vertebral arteries and the circle of Willis),
      extracranial arteries, the aortic arch, and the heart. RESULTS: A total of 45
      patients with MI-MCA were identified. Their median (range) survival time was 6 (0
      to 20) days as compared with 18 (0 to 2,040) days for non-MI-MCA patients.
      Compared with non-MI-MCA, MI-MCA cases more frequently involved the superficial
      and deep MCA territory and were more frequently associated with anterior cerebral
      and anterior choroidal artery territory infarcts. Hemorrhagic transformation,
      Duret hemorrhages, carotid occlusion, and ipsilateral abnormalities of the circle
      of Willis were also more frequent (p < 0.05). Multivariable analysis showed that
      younger age, female sex, absence of stroke history, higher heart weight, carotid
      artery occlusion, and abnormal circle of Willis ipsilaterally were all
      independently associated with MI-MCA (p < 0.03). CONCLUSIONS: Typical pathologic
      pattern for development of malignant infarction of the middle cerebral artery is
      a carotid occlusion with abnormal ipsilateral circle of Willis in a young patient
      who had a first-ever large hemispheric stroke including the superficial territory
      with possibly a slight predominance of female sex.

PMID- 16567698
TI  - Risk factors for transitions from normal to mild cognitive impairment and
      dementia.
AB  - OBJECTIVE: To identify risk factors associated with transitions from cognitively
      normal to various forms of mild cognitive impairment (MCI) and then from MCI into
      early dementia with death as a competing state. METHODS: Cognitive assessments
      from 554 subjects participating in a longitudinal study at the University of
      Kentucky AD Center were used to classify individuals into one of three transient
      states at any visit: cognitively normal, amnestic MCI, or mixed MCI. Between
      visits subjects could die or become demented. A series of polytomous logistic
      models were used to model transitions among these states over time and to
      determine how the log odds of these transitions vary with age, education, sex,
      family history of dementia, and APOE status. RESULTS: Age affects all transitions
      among transient states as well as those to dementia or death. Presence of at
      least one apolipoprotein 4 allele affects transitions from cognitively normal
      into amnestic MCI or into dementia. At most 12 years of education affects
      transitions into mixed MCI. Transitions do not vary with sex or family history.
      CONCLUSION: Aside from age, the usual risk factors associated with conversion
      from cognitively normal into dementia are likely risk factors for transitions
      into mild cognitive impairment.

PMID- 16567699
TI  - Contrasting cognitive trajectories of impending death and preclinical dementia in
      the very old.
AB  - BACKGROUND: Both impending death and preclinical dementia are associated with
      cognitive impairment in old age, although their effects on cognitive functioning
      have rarely been examined within the same study. METHODS: Participants (n =
      1,200, aged 75+ years) from a community-based study completed a measure of global
      cognitive performance (the Mini-Mental State Examination [MMSE]) at 3-year
      intervals over an 11-year period. Level and change of MMSE performance were
      compared for three groups: persons in close proximity to death, persons in a
      preclinical phase of dementia, and persons who remained alive and nondemented
      throughout the study. RESULTS: There were significant group differences in MMSE
      performance 3 years before each outcome (death, dementia, or end of study). Those
      with preclinical dementia performed the poorest and declined twice as fast on the
      MMSE relative to the other groups. Although persons in close proximity to death
      declined faster in general, no accelerated decline was observed for the impending
      death group after persons with dementia or preclinical dementia had been
      excluded. Group differences were attenuated for the oldest-old (81+ years)
      compared to the old-old (75 to 80 years). CONCLUSIONS: The lack of accelerated
      decline in proximity to death after excluding persons with dementia or
      preclinical dementia suggests that part of the terminal decline effect
      demonstrated in previous investigations may reflect preclinical dementia
      deficits. Further, accelerated cognitive decline might be a more reliable
      indicator of preclinical dementia than a low cognitive score due to confounds
      associated with cross-sectional cognitive performance.

PMID- 16567701
TI  - Axonal damage markers in cerebrospinal fluid are increased in ALS.
AB  - OBJECTIVE: To test whether biomarkers for axonal degeneration correlated with
      clinical subtypes and were of use in predicting progression of ALS. METHODS:
      Patients with ALS (n = 69), patients with Alzheimer disease (AD; n = 73), and age
      matched controls (n = 33) were included in this prospective study. CSF levels of
      tau protein and neurofilaments (NfHSMI35) were measured using ELISA. In 49
      patients with ALS, follow-up data were available (median follow-up 7 months).
      RESULTS: CSF levels of NfHSMI35 were five times higher in patients with ALS (1.7
      ng/mL) than in controls (0.3 ng/mL, p < 0.001) and 10 times higher than in
      patients with AD (0.14 ng/mL, p < 0.001). NfHSMI35 values were also higher in
      patients with upper motor neuron-dominant ALS than in patients with typical ALS
      (upper motor neuron + lower motor neuron) at p = 0.02. Values of NfHSMI35 were
      higher in ALS of more rapid progression. The values of NfH and tau did not
      correlate with CSF protein content. CONCLUSIONS: The authors propose that axonal
      damage markers in CSF may discriminate between subtypes of ALS and that they
      could be used as markers for therapeutic trials. CSF NfH was superior to tau in
      these discriminations.

PMID- 16567700
TI  - Potential early markers of Parkinson disease in idiopathic REM sleep behavior
      disorder.
AB  - BACKGROUND: Idiopathic REM sleep behavior disorder (RBD) is characterized by loss
      of atonia during REM sleep, resulting in motor activity during dreams. Studies
      estimate that approximately half of patients with RBD will eventually develop
      Parkinson disease (PD), so RBD may be an indicator of presymptomatic PD. Several
      potential early diagnostic markers of PD have been proposed, but they have
      generally not been tested in presymptomatic PD. The authors hypothesized that
      these markers may be abnormal in idiopathic RBD. METHODS: The authors compared 25
      patients with polysomnography-confirmed RBD without PD with age- and sex-matched
      controls. Color vision, olfaction, quantitative motor testing, and indices of
      depression, personality, and autonomic function were examined. RESULTS: Patients
      demonstrated significant impairment in color discrimination and olfactory
      function. Patients had subtle abnormalities on quantitative testing of motor and
      gait speed. Autonomic symptoms were more common in patients than controls.
      Abnormalities were heterogeneous, with some patients scoring normally on all
      domains, whereas others were severely impaired on multiple domains. Dysfunction
      on tests of olfactory function, color vision, and motor speed were highly
      correlated, such that patients who performed poorly on one test tended to perform
      poorly on the others. CONCLUSIONS: Many potential early markers of Parkinson
      disease are significantly abnormal in idiopathic REM sleep behavior disorder.
      These abnormalities are present in approximately half of the patients, suggesting
      a heterogenous pathophysiology.

PMID- 16567702
TI  - Is skin biopsy a predictor of transition to symptomatic HIV neuropathy? A
      longitudinal study.
AB  - OBJECTIVE: To investigate whether serially assessed epidermal nerve fiber (ENF)
      density and quantitative sensory thresholds (QSTs) are associated with the
      clinical transition from HIV infection with no neuropathy or asymptomatic
      neuropathy to symptomatic distal sensory neuropathy (SDSP). BACKGROUND:
      Identifying predictors of transition to SDSP would enable identification of
      subjects at enhanced risk for development of HIV-SDSP and facilitate intervention
      studies with the ultimate goal of disease prevention. Asymptomatic signs of
      sensory dysfunction in the feet have been shown to be weakly predictive of SDSP;
      however, bedside evaluation of small sensory fibers is limited. Abnormality of
      these fibers may play an important role in the genesis of SDSP. METHODS: Fifty
      eight HIV-infected subjects underwent serial clinical, virologic, immunologic,
      skin biopsy, and QST assessments. Cox proportional hazards modeling was used to
      examine the associations of serial ENF density and QST assessments with the risk
      of development of SDSP among the subset of 26 subjects who had asymptomatic or no
      neuropathy at study entry. RESULTS: Median follow-up was 2.9 years (range 6
      months to 4.5 years) during which 19 of 26 subjects transitioned to SDSP. Using a
      model where ENF density and QST measures from the study visit before potential
      transition were examined, a lower leg ENF density, a higher cooling threshold,
      and a higher heat pain threshold for minimal pain (HP 0.5) were associated with a
      greater risk of SDSP in univariate analyses. In multiple regression analyses, leg
      ENF density but not QST measures were significantly associated with SDSP. A leg
      ENF density of 10 fibers/mm or less conferred a 14-fold greater risk of SDSP than
      a leg ENF density greater than 10 fibers/mm. CONCLUSIONS: Measures of small
      sensory fibers (leg epidermal nerve fiber density, cooling and heat pain
      thresholds) seem to be associated with transition to symptomatic HIV-associated
      distal sensory neuropathy 6 to 12 months later.

PMID- 16567703
TI  - Caudate blood flow and volume are reduced in HIV+ neurocognitively impaired
      patients.
AB  - OBJECTIVE: To evaluate the effects of HIV-associated neurocognitive impairment on
      caudate blood flow and volume. METHODS: The authors performed continuous arterial
      spin labeled MRI on 42 HIV+ patients (23 subsyndromic and 19 HIV
      neurosymptomatic) on highly active antiretroviral therapy and 17 seronegative
      controls. They compared caudate blood flow and volume among groups. RESULTS: A
      stepwise decrease in both caudate blood flow and volume was observed with
      increasing HIV-associated neurocognitive impairment. Compared with seronegative
      controls, baseline caudate blood flow was reduced in HIV+ neurosymptomatic
      patients (p = 0.001) with a similar decreasing trend for subsyndromic HIV+
      patients (p = 0.070). Differences in caudate volume were observed only for
      neurosymptomatic HIV+ patients compared with controls (p = 0.010). A Jonckheere
      Terpstra test for trends was significant for both caudate blood flow and volume
      for each of the three subgroups. Pearson product moment correlation coefficients
      were not significant between caudate blood flow and volume for each group.
      CONCLUSIONS: Decreasing trends in caudate blood flow and volume were associated
      with significantly increasing HIV-associated neurocognitive impairment (HNCI),
      with the greatest decreases observed for more severely impaired patients.
      However, reductions in caudate blood flow and volume were poorly correlated.
      Changes in residual caudate blood flow may act as a surrogate biomarker for
      classifying the degree of HNCI.

PMID- 16567704
TI  - Antiretroviral use and other risks for HIV-associated neuropathies in an
      international cohort.
AB  - OBJECTIVE: To explore the association between specific nucleoside reverse
      transcriptase inhibitors and sensory neuropathies (SNs) and define the modifying
      roles of hepatitis C (HCV), vitamin B12 deficiency, and impaired glucose
      tolerance. METHODS: The authors conducted a prospective cohort study of 147 HIV
      infected adults at two sites chosen to emphasize demographic differences.
      Standardized assessments included detailed antiretroviral histories, neurologic
      examinations, skin biopsies for epidermal nerve quantitation, and quantitative
      sensory testing. RESULTS: There were significant differences between subjects at
      Johns Hopkins University (JHU) and Monash University (MU) in gender, race, HIV
      transmission route, and HCV seroprevalence. Symptomatic SN was present in 49% at
      JHU and 55% at MU (chi2 = 4.02, p = 0.134) and was significantly more common in
      those at least age 40 than younger patients (odds ratio [OR] = 2.87, 95% CI =
      1.27, 6.49). After adjusting for site, age, and CD4 cell count, exposure to
      didanosine (ddI) or stavudine (d4T) was associated with an significantly
      increased likelihood of symptomatic SN (ddI: OR = 3.21, 95% CI: 1.56, 6.60; d4T:
      OR = 7.66, 95% CI: 2.89, 20.33). Plasma HIV RNA, lactate, and HCV were not
      associated with SN. Quantitative vibratory testing identified neuropathy with a
      positive predictive value of 76% and epidermal nerve fiber densities 59%.
      CONCLUSIONS: Exposure to stavudine and didanosine was significantly associated
      with a heightened risk for symptomatic sensory neuropathy. Reduced vibration
      thresholds and epidermal nerve fiber densities had the highest diagnostic
      efficiency of the laboratory indicators of neuropathy examined, but were
      relatively insensitive in isolation.

PMID- 16567705
TI  - Cerebral metabolites in HIV-infected children followed for 10 months with 1H-MRS.
AB  - BACKGROUND: Previous studies have shown that HIV-infected children have abnormal
      cerebral metabolites, measured by proton MR spectroscopy (1H MRS), but the
      stability of these measurements over time has not been described in HIV-infected
      children. The authors recently reported a study of cerebral metabolites in 20 HIV
      infected children (6 to 16 years of age); the current study followed 12 of these
      children (10.0 years +/- 3.7 years) and repeated the MR spectroscopy at 24.1 +/-
      3.7 weeks and 42.2 +/- 3.5 weeks following the entry time with repeated
      neuropsychological testing. METHODS: 1H MR spectra were acquired at 1.5 T (GE
      Signa, PRESS localization, repetition time = 3,000 msec, echo time = 30 msec).
      Five brain regions were studied: right frontal white matter, left frontal white
      matter, right basal ganglia, right hippocampus, and midfrontal gray matter. The
      concentrations of N-acetylaspartate (NAA), choline (CHO), creatine (CR), and myo
      inositol (mI) and the ratio of each metabolite to CR were determined. RESULTS:
      There were no changes in the metabolite concentrations or metabolite/CR ratios at
      the three time periods. Similarly, during this follow-up period, HIV-positive
      children showed no changes in clinical signs, HIV viral loads, CD4%, or CD4
      counts, except for improved spatial memory with repeat testing. CONCLUSION: In a
      clinically and neurologically stable group of HIV-infected children, cerebral
      metabolites were stable over a 10-month time period, suggesting that it is
      possible to assess changes in cerebral metabolites as a measure of cerebral
      health, but longer follow-up in a larger sample is needed.

PMID- 16567706
TI  - Basilar-type migraine: clinical, epidemiologic, and genetic features.
AB  - BACKGROUND: It remains uncertain whether basilar-type migraine (BM) is a subtype
      of migraine with typical aura (MTA) or a distinct phenotype or genotype.
      OBJECTIVE: To analyze the symptomatology, familial distribution, and genotype of
      BM. METHODS: The authors recruited 105 families comprising 362 patients with MTA
      or BM (International Classification of Headache Disorders-1 criteria). Among
      these patients, 38 patients from 29 families had BM. In 12 of the families with
      BM with an apparently dominant inheritance the authors sequenced all exons of the
      CACNA1A (chromosome 19) and ATP1A2 (chromosome 1) genes responsible for most
      cases of the autosomal dominantly inherited familial hemiplegic migraine and
      performed a linkage analysis of chromosome 1 and 19 with a nonparametric or
      autosomal dominant parametric model using an affected only analysis. RESULTS: BM
      occurred in 10% (38/362) of patients with MTA. The basilar-type aura had a median
      duration of 60 minutes and comprised vertigo 61%, dysarthria 53%, tinnitus 45%,
      diplopia 45%, bilateral visual symptoms 40%, bilateral paresthesias 24%,
      decreased level of consciousness 21%, hypacusia 21%, and ataxia 5%. The relative
      frequency of the individual basilar-type symptoms was not different from patients
      with hemiplegic migraine from a previous study. The patients with BM were equally
      distributed among the 105 families with MTA (p = 0.37). The attacks of MTA were
      identical in families with or without BM. No causative mutations and no linkage
      was identified. CONCLUSIONS: Basilar-type aura seemingly may occur at times in
      any patient with migraine with typical aura. There is no firm clinical,
      epidemiologic, or genetic evidence that BM is an independent disease entity
      different from MTA.

PMID- 16567707
TI  - Humor and smiling: cortical regions selective for cognitive, affective, and
      volitional components.
AB  - BACKGROUND: The interrelationships among humor, smiling, and grinning have
      fascinated philosophers for millennia and neurologists for over a century. A
      functional dissociation between emotional facial expressions and those under
      voluntary control was suggested decades ago. Recent functional imaging studies,
      however, have been somewhat at odds with older studies with respect to the role
      of the right frontal cortex in the perception of humor. METHODS: Blood oxygen
      level-dependent (BOLD) activity was measured in 13 subjects during the
      presentation of "funny" vs "nonfunny" versions of essentially the same cartoons
      and compared with BOLD activity associated with "merely grinning" at similar
      nonfunny cartoons via fMRI. RESULTS: Humor perception was correlated with BOLD
      activity in the left temporo-occipitoparietal junction and left prefrontal cortex
      and humor-associated smiling (recorded with an MR-compatible video camera) with
      bilateral activity in the basal temporal lobes. Unexpectedly, both conditions
      were also accompanied by a decrease in BOLD activity in the right orbitofrontal
      cortex. Voluntary "grinning" in the absence of humorous stimuli was accompanied
      by bilateral activity in the facial motor regions. CONCLUSIONS: These results
      confirm the clinically derived hypothesis of separate cortical regions
      responsible for the production of emotionally driven vs voluntary facial
      expressions. The right orbitofrontal decrease reconciles inconsistencies between
      clinical and functional imaging findings and may reflect a disinhibition of
      facial emotional expression.

PMID- 16567708
TI  - A Phase II study of the safety and efficacy of teriflunomide in multiple
      sclerosis with relapses.
AB  - BACKGROUND: Teriflunomide, a dihydro-orotate dehydrogenase inhibitor, has
      immunomodulatory effects, including the ability to suppress experimental allergic
      encephalomyelitis. In this randomized, double-blind, placebo-controlled Phase II
      study, the authors examined the safety and efficacy of oral teriflunomide in
      multiple sclerosis (MS) with relapses. METHODS: Patients (n = 179) with relapsing
      remitting MS (n = 157) or secondary progressive MS with relapses (n = 22) were
      randomized to receive placebo, teriflunomide 7 mg/day, or teriflunomide 14 mg/day
      for 36 weeks. MRI brain scans were performed every 6 weeks. The primary endpoint
      was the number of combined unique active lesions per MRI scan. Secondary
      endpoints included MRI-defined disease burden, relapse frequency, and disability
      increase. RESULTS: The median number of combined unique active lesions per scan
      was 0.5, 0.2, and 0.3 in the placebo, teriflunomide 7 mg/day (p < 0.03 vs
      placebo), and teriflunomide 14 mg/day (p < 0.01 vs placebo) groups during the 36
      week double-blind treatment phase. Teriflunomide-treated patients also had
      significantly fewer T1 enhancing lesions per scan, new or enlarging T2 lesions
      per scan, and new T2 lesions. Patients receiving teriflunomide 14 mg/day had
      significantly reduced T2 disease burden. Teriflunomide treatment resulted in
      trends toward a lower annualized relapse rate and fewer relapsing patients (14
      mg/day only) vs placebo. Significantly fewer patients receiving teriflunomide 14
      mg/day vs placebo demonstrated disability increase. Treatment was well tolerated;
      numbers of adverse events and serious adverse events were similar in all
      treatment groups. CONCLUSION: Oral teriflunomide was effective in reducing MRI
      lesions and was well tolerated in patients with relapsing multiple sclerosis.

PMID- 16567709
TI  - Natural history of homonymous hemianopia.
AB  - OBJECTIVE: To describe the characteristics of spontaneous recovery of homonymous
      hemianopia (HH). METHODS: The authors reviewed medical records of all patients
      with HH confirmed by formal visual field testing and seen in follow-up in their
      service between 1989 and 2004. Clinical characteristics, causes, neuroradiologic
      definition of lesion location, final outcome, and evolution of the visual field
      defects were recorded. The associations among final visual field defect outcome,
      time from injury, and clinical features were analyzed. RESULTS: A total of 254
      patients with 263 HH were included in this study. Spontaneous visual field defect
      recovery was observed in 101 HH (38.4%). The likelihood of spontaneous recovery
      decreased with increasing time from injury to initial visual field testing (p =
      0.0003). The probability of improvement was related to the time since injury (p =
      0.0003) with a 50 to 60% chance of improvement for cases tested within 1 month
      after injury that decreased to about 20% for cases tested at 6 months after
      surgery. No other factor was found to correlate with the final outcome of the
      visual field defects. Improvement after 6 months from injury was mild and usually
      related to improvement of the underlying disease. CONCLUSION: Spontaneous
      improvement of homonymous hemianopia is seen in at least 50% of patients first
      seen within 1 month of injury. In most cases, the improvement occurs within the
      first 3 months from injury. Spontaneous improvement after 6 months postinjury
      should be interpreted with caution as it is most likely related to improvement of
      the underlying disease or to improvement in the patient's ability to perform
      visual field testing reliably.

PMID- 16567710
TI  - Homonymous hemianopias: clinical-anatomic correlations in 904 cases.
AB  - OBJECTIVE: To describe the clinical characteristics and clinical-anatomic
      correlations of homonymous hemianopia (HH). BACKGROUND: Homonymous hemianopia
      impairs visual function and frequently precludes driving. Most knowledge of HH is
      based on relatively few cases with clinical-anatomic correlations. METHODS: The
      authors reviewed medical records of all patients with HH seen in their service
      between 1989 and 2004. Demographic characteristics, characteristics of visual
      field defects, causes of visual field defects, neuroradiologic definition of
      lesion location, and associated neurologic deficits were recorded. RESULTS: A
      total of 904 HH were found in 852 patients. A total of 340 HH (37.6%) were
      complete and 564 HH (62.4%) were incomplete. Homonymous quadrantanopia (264 HH,
      29%) was the most common type of incomplete HH, followed by homonymous
      scotomatous defects (116 HH, 13.5%), partial HH (114 HH, 13%), and HH with
      macular sparing (66 HH, 7%). A total of 407 HH (45.0%) were isolated. Causes of
      HH included stroke (629 HH, 69.6%), trauma (123, 13.6%), tumor (102, 11.3%),
      brain surgery (22, 2.4%), demyelination (13, 1.4%), other rare causes (13, 1.4%),
      and unknown etiology (2, 0.2%). The lesions were most commonly located in the
      occipital lobes (45%) and the optic radiations (32.2%). Every type of HH, except
      for unilateral loss of temporal crescent and homonymous sectoranopia, was found
      in all lesion locations along the retrochiasmal visual pathways. CONCLUSION:
      Homonymous hemianopia is usually secondary to stroke, head trauma, and tumors.
      Although the characteristics of visual field defects can be helpful in lesion
      location, specific visual field defects do not always indicate specific brain
      locations.

PMID- 16567712
TI  - Transient prosopagnosia after ischemic stroke.

PMID- 16567711
TI  - A randomized, double-blind trial of bromocriptine efficacy in nonfluent aphasia
      after stroke.
AB  - The authors assessed the efficacy of bromocriptine in nonfluent aphasia after
      stroke in a 16-week, randomized, double-blind, placebo-controlled clinical trial
      conducted from June 2002 to April 2004. In all 38 patients after 4 months of
      treatment, improvement in both the bromocriptine and placebo treatment groups was
      observed (p < 0.001). The analysis of repeated-measures analysis of variance
      revealed bromocriptine did not improve nonfluent aphasia.

PMID- 16567713
TI  - Multifocal neuropathy due to plasma cell infiltration of peripheral nerves in
      multiple myeloma.
AB  - Patients with multiple myeloma (MM) can manifest a variety of neurologic
      complications. The authors report two patients who had development of a
      multifocal neuropathy related to infiltration of peripheral nerves by malignant
      plasma cells as the only manifestation of a relapse of MM, which was considered
      in full remission.

PMID- 16567714
TI  - Childhood-onset multifocal motor neuropathy with conduction blocks.
AB  - Multifocal motor neuropathy (MMN) is an acquired disorder with onset in
      adulthood. The authors describe a patient with a slowly progressing distal upper
      limb motor neuropathy since age 6 years, in whom definite conduction blocks in
      upper limbs, outside common entrapment sites, and no sensory involvement were
      consistent with MMN. IV immunoglobulin treatment produced marked muscle strength
      improvement and conduction block disappearance. MMN diagnosis should also be
      considered in childhood.

PMID- 16567715
TI  - Intronic mutation in the PGK1 gene may cause recurrent myoglobinuria by aberrant
      splicing.
AB  - A 33-year-old man with mental retardation and recurrent myoglobinuria
      demonstrated a deficiency in the phosphoglycerate kinase 1 (PGK1) activity of his
      muscles and erythrocytes. His PGK1 gene had intronic G-to-A substitution 5
      nucleotides downstream from the normal exon 7 5' splice site (IVS7 + 5 G>A). This
      novel mutation results in a frame shift due to the insertion of 52 bp of intron 7
      in the mature mRNA by aberrant splicing.

PMID- 16567716
TI  - Frequency of spinal arteriovenous malformations in patients with unexplained
      myelopathy.
AB  - The authors reviewed charts of 78 myelopathy patients who underwent spinal
      angiography for possible arteriovenous malformations (AVMs). Twenty-two patients
      had an AVM. No neurologic complications from angiography were observed. MRI
      findings of increased T2 signal or flow voids were strongly associated with AVMs.
      Spinal angiography should be performed in all patients with unexplained
      myelopathy after neurologic evaluation and an MRI demonstrating increased T2
      signal or flow voids.

PMID- 16567717
TI  - Electrophysiologic characterization in spinocerebellar ataxia 17.
AB  - The authors performed a multimodal electrophysiologic evaluation in nine patients
      belonging to four SCA17 (spinocerebellar ataxia type 17) families. Peripheral
      nerve and visual system were not involved. Brainstem auditory evoked potentials
      were constantly abnormal with central type lesions. Magnetic motor evoked
      potentials were abnormal only in the lower limbs, suggesting a length-dependent
      involvement of the pyramidal tract. Somatosensory evoked potentials were abnormal
      in almost all our patients, and abnormalities were consistent with a
      somatosensory pathway involvement along the brainstem.

PMID- 16567718
TI  - Correlation of visual hallucinations with occipital rCBF changes by donepezil in
      DLB.
AB  - The authors explored the neural substrate of visual hallucinations in dementia
      with Lewy bodies (DLB) by investigating changes in regional cerebral blood flow
      (rCBF) and psychiatric symptoms, before and after cholinesterase inhibitor
      treatment. Twenty subjects with DLB were treated with donepezil for a 12-week
      period. Hallucinations attenuated while receiving therapy, whereas occipital rCBF
      focally increased, suggesting that functional visual association cortex deficits
      may cause visual hallucinations in patients with DLB.

PMID- 16567719
TI  - Relationship between Helicobacter pylori infection and Alzheimer disease.
AB  - The authors investigated the association between Helicobacter pylori infection
      (Hp-I) and Alzheimer disease (AD) by using histology for diagnosis of Hp-I. Fifty
      patients with AD and 30 iron deficiency anemic control participants without AD
      were included. The histologic prevalence of Hp-I was 88% in patients with AD and
      46.7% in controls (p < 0.001).

PMID- 16567720
TI  - What is the risk of developing parkinsonism following neuroleptic use?
AB  - Use of neuroleptic medications is common among elderly patients. Using
      multivariate models, the authors found that use of antipsychotic medications,
      age, and disability were strong predictors of developing self-reported Parkinson
      disease (PD) in the subsequent year among 1992 to 2000 Medicare Current
      Beneficiary Survey participants. Although more research is needed, these data
      suggest that 126 Medicare beneficiaries would need to be treated with neuroleptic
      medications to cause one additional case of self-reported PD.

PMID- 16567722
TI  - MRI characteristics of cerebral air embolism from a venous source.

PMID- 16567721
TI  - Central respiratory dysfunction following vertebral artery dissection.

PMID- 16567724
TI  - Does sensory Guillain-Barre syndrome exist without any abnormalities in motor
      nerve conduction?

PMID- 16567723
TI  - Migraine with aura associated with reversible MRI abnormalities.

PMID- 16567725
TI  - Rheumatoid leptomeningitis after heart transplantation.

PMID- 16567726
TI  - Penguins and hummingbirds: midbrain atrophy in progressive supranuclear palsy.

PMID- 16567727
TI  - Lack of association with TorsinA haplotype in German patients with sporadic
      dystonia.

PMID- 16567728
TI  - Dwelling place.

PMID- 16567729
TI  - Long-term results of tacrolimus in cyclosporine- and prednisone-dependent
      myasthenia gravis.

PMID- 16567730
TI  - Prevalence of bipolar symptoms in epilepsy vs other chronic health disorders.

PMID- 16567731
TI  - A randomized controlled trial of surgery vs steroid injection for carpal tunnel
      syndrome.

PMID- 16567732
TI  - Polyneuropathy associated with interferon beta treatment in patients with
      multiple sclerosis.

PMID- 16567733
TI  - The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and
      Hispanics.

PMID- 16567734
TI  - Depression is associated with impairment of ADL, not motor function in Parkinson
      disease.

PMID- 16567735
TI  - Improved tolerability and efficacy in epilepsy patients with extended-release
      carbamazepine.

PMID- 16567737
TI  - Neurologic links between epilepsy and depression in women: is hippocampal
      neuroplasticity the key?
AB  - Recent advances in our understanding of the actions of sex steroids on the brain
      and the pathophysiology of depression have provided a hypothetical framework that
      may functionally connect epilepsy, ovarian hormone levels, and depression. The
      hippocampus plays a critical role in both seizure activity and mood disorders,
      which suggests that pathology in this area of the brain might provide a link
      between epilepsy and depression. Recent findings support the view that
      neurogenesis is not the only factor that contributes to the pathomechanism of
      depression and antidepressant responses, which may involve other hippocampal
      cellular or molecular changes, or both. Specifically, remodeling of the
      hippocampal spine synapses may play a significant role in the neurobiology of
      depression and the effects of antidepressant therapy. Because the effects of
      estrogens on hippocampal synaptogenesis parallel those of antidepressants, loss
      of estrogen appears to be a critical contributor to the etiology of depressive
      disorders. The increased incidence of depression observed in women with epilepsy
      might therefore reflect a hormonal deficiency state because epilepsy is
      frequently associated with defects in reproductive function. In women with
      catamenial epilepsy, changes in gonadal steroid production are seen to link
      seizure frequency with reproductive state, emphasizing the importance of gonadal
      steroid levels not only in depression but also in seizure activity. Paradoxical
      features of epilepsy, i.e., seizure-induced increases in hippocampal neurotrophin
      expression and neurogenesis, suggest that the most important factor in the
      neurobiology of depression might be the extent to which the hippocampus can adapt
      appropriately to changes in the environment through alterations in hippocampal
      synaptic connectivity.

PMID- 16567738
TI  - Menstrual disorders in women with epilepsy.
AB  - Women with epilepsy are more likely to have menstrual disorders than women in the
      general population. Estimates vary because of different definitions of menstrual
      disorder. Our best estimate is that perhaps one of every three women with
      epilepsy may be affected compared with one of seven in the general population.
      Menstrual disorders are significant because they are associated with anovulatory
      cycles that may increase the risks for infertility, migraine, emotional
      disorders, and female cancers. They are neurologically important because they are
      associated with greater seizure frequency. Increasing evidence implicates both
      epilepsy itself and antiepileptic drug (AED) use as causal or contributory
      factors. These factors can alter reproductive hormone levels and promote the
      development of reproductive endocrine disorders, especially polycystic ovarian
      syndrome (PCOS). Among AEDs, valproate has been associated with the development
      of characteristic PCOS features. The risk appears to be particularly high when
      valproate use is started in childhood or adolescence. Menopause tends to occur
      earlier in women with epilepsy, especially in the setting of a high lifetime
      number of seizures and lifetime use of multiple enzyme-inducing AEDs. The
      intricate relationship between reproductive disorders and epilepsy suggests that
      reproductive function should be monitored closely as part of the comprehensive
      care of women with epilepsy.

PMID- 16567739
TI  - An overview of oral contraceptives: mechanism of action and clinical use.
AB  - Hormonal contraception is available in oral contraceptive pills and in newer
      formulations, including the transdermal patch, the vaginal ring, subcutaneous
      implants, and IM injections. Prevention of pregnancy is achieved by inhibiting
      ovulation, fertilization, and/or implantation of an egg. Hormonal contraception
      provides effective, tolerable, and reversible prevention of pregnancy. Efficacy
      and safety profiles are similar for different formulations and administration
      routes. Lowest expected failure (i.e., method failure) rates for hormonal
      contraceptives, regardless of formulation, are <2%. Typical failure rates for
      oral formulations range from <3% to 5% due to failures in compliance. The most
      commonly reported adverse effects are weight gain, nausea, variations in
      menstrual flow, breast changes such as tenderness, discomfort, or swelling,
      depression or mood disturbances, decreased sexual desire or response, and acne.
      Rare but serious potential effects include cardiovascular diseases, such as
      stroke, and an increased risk for breast cancer, liver tumors, and gallbladder
      disease. Hormonal contraceptive use should be avoided in women at risk for blood
      clots, by heavy smokers, and in women with breast or other cancers. Use of
      hormonal contraception in adolescents requires special consideration, in part
      because of decreased compliance.

PMID- 16567741
TI  - Antiepileptic drugs and hormonal contraceptives in adolescent women with
      epilepsy.
AB  - Both estrogen and progesterone influence seizure activity in women with epilepsy,
      with estrogen generally demonstrating proconvulsant and progesterone
      anticonvulsant effects. Women with epilepsy exhibit a variety of endocrine
      disturbances, probably due to a combination of factors, including the epilepsy
      syndrome and the effect of interictal and ictal epileptic discharges in the
      brain. The direct effects of some antiepileptic drugs (AEDs) further increase
      this risk, apparently related to a specific drug's effect on hepatic microsomal
      enzymes of the cytochrome P-450 system. AEDs that induce hepatic microsomal
      enzymes also interact with hormonal contraception to increase estrogen's
      metabolism and progesterone's protein binding, decreasing concentrations of both
      hormones and thus reducing contraceptive efficacy. Some evidence indicates that
      concurrent use of hormonal contraceptives and lamotrigine significantly decreases
      the plasma concentration of lamotrigine, suggesting that close monitoring is
      warranted. Nevertheless, hormonal contraception confers comparable or superior
      efficacy compared with such other contraceptives as the intrauterine device and
      barrier methods and remains an appropriate option in women with epilepsy.
      Importantly, concurrent use of hormonal contraception and AEDs does not adversely
      affect seizure control. Careful patient management, including the use of
      increased estrogen doses (> or =50 microg) in patients receiving enzyme-inducing
      AEDs, may further minimize the risk for unintended pregnancy. Special
      considerations in women of childbearing age include decreased compliance and
      disease prevention. Although adequate seizure control is the critical requirement
      of an AED, the potential for interactions with hormonal contraception and the
      increased risk for endocrine disturbances caused by drugs that alter hepatic
      microsomal enzymes suggest additional potential advantages for AED treatment that
      does not affect these enzymes. Both the constellation of physicians treating
      women with epilepsy and the patients themselves have a poor understanding of the
      spectrum of reproductive health issues involved, and increased awareness is
      needed to improve patient management.

PMID- 16567744
TI  - Depression and suicide in adolescents with epilepsy.
AB  - Depression and other disorders are underdiagnosed and undertreated in young
      people with epilepsy. Signs of depression are often dismissed as "normal"
      reactions, even though depression is a life-threatening disease and a risk factor
      for suicide. A strong correlation between epilepsy and depression has been
      demonstrated in a variety of studies; etiological factors include neurologic,
      genetic, and iatrogenic factors. At the time of the initial diagnostic
      evaluation, the physician who is managing the patient with seizure disorder
      should make a psychiatric and psychosocial assessment to identify the patient's
      risk for depression. This approach enables the physician to assess the impact of
      epilepsy on the patient and to detect gross signs of psychiatric disorder.
      Effective treatment options include both somatic and nonsomatic therapies as well
      as combinations thereof.

PMID- 16567745
TI  - Nurse practitioners now able to work across Canada.

PMID- 16567746
TI  - For-profit clinic founder is CMA's new president-elect.

PMID- 16567747
TI  - Canadian helps WHO with pandemic.

PMID- 16567748
TI  - STIs a "hidden epidemic": SOGC.

PMID- 16567751
TI  - Does glycemic control with insulin therapy play a role for critically ill
      patients in hospital?

PMID- 16567752
TI  - Can you prevent adverse drug events after hospital discharge?

PMID- 16567753
TI  - Poverty and health.

PMID- 16567754
TI  - A child with fever, hip pain and limp.

PMID- 16567755
TI  - Intravenously administered vitamin C as cancer therapy: three cases.
AB  - Early clinical studies showed that high-dose vitamin C, given by intravenous and
      oral routes, may improve symptoms and prolong life in patients with terminal
      cancer. Double-blind placebo-controlled studies of oral vitamin C therapy showed
      no benefit. Recent evidence shows that oral administration of the maximum
      tolerated dose of vitamin C (18 g/d) produces peak plasma concentrations of only
      220 micromol/L, whereas intravenous administration of the same dose produces
      plasma concentrations about 25-fold higher. Larger doses (50-100 g) given
      intravenously may result in plasma concentrations of about 14,000 micromol/L. At
      concentrations above 1000 micromol/L, vitamin C is toxic to some cancer cells but
      not to normal cells in vitro. We found 3 well-documented cases of advanced
      cancers, confirmed by histopathologic review, where patients had unexpectedly
      long survival times after receiving high-dose intravenous vitamin C therapy. We
      examined clinical details of each case in accordance with National Cancer
      Institute (NCI) Best Case Series guidelines. Tumour pathology was verified by
      pathologists at the NCI who were unaware of diagnosis or treatment. In light of
      recent clinical pharmacokinetic findings and in vitro evidence of anti-tumour
      mechanisms, these case reports indicate that the role of high-dose intravenous
      vitamin C therapy in cancer treatment should be reassessed.

PMID- 16567756
TI  - High-dose vitamin C therapy: renewed hope or false promise?

PMID- 16567757
TI  - Prescribing exercise as preventive therapy.
AB  - Energy expenditure of about 1000 kcal (4200 kJ) per week (equivalent to walking 1
      hour 5 days a week) is associated with significant health benefits. Health
      benefits can be achieved through structured or nonstructured physical activity,
      accumulated throughout the day (even through short 10-minute bouts) on most days
      of the week. In this article we outline the means of evaluating cardiovascular
      and musculoskeletal fitness, the methods of evaluating physical activity levels,
      the current recommendations for exercise (including intensity, type, time and
      frequency) and the resources available for patients and physicians interested in
      learning more about the evaluation of physical activity and fitness levels and
      the prescription of exercise.

PMID- 16567759
TI  - Colon cancer screening.

PMID- 16567760
TI  - Colon cancer screening.

PMID- 16567761
TI  - Conjugate vaccines and polysaccharide response.

PMID- 16567762
TI  - Unnecessary distraction for specialist physicians.

PMID- 16567763
TI  - Sentinel node micrometastases and non-sentinel nodes in breast cancer: how much
      do we need to know?

PMID- 16567764
TI  - Cancer in the elderly population: the protection racket.

PMID- 16567765
TI  - Have we found the ultimate risk factor for breast cancer?

PMID- 16567766
TI  - Estrogen receptor testing of breast cancer in current clinical practice: what's
      the question?

PMID- 16567767
TI  - New horizons in staging for non-small-cell lung cancer.

PMID- 16567768
TI  - Genomics identifies medulloblastoma subgroups that are enriched for specific
      genetic alterations.
AB  - PURPOSE: Traditional genetic approaches to identify gene mutations in cancer are
      expensive and laborious. Nonetheless, if we are to avoid rejecting effective
      molecular targeted therapies, we must test these drugs in patients whose tumors
      harbor mutations in the drug target. We hypothesized that gene expression
      profiling might be a more rapid and cost-effective method of identifying tumors
      that contain specific genetic abnormalities. MATERIALS AND METHODS: Gene
      expression profiles of 46 samples of medulloblastoma were generated using the
      U133av2 Affymetrix oligonucleotide array and validated using real-time reverse
      transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry.
      Genetic abnormalities were confirmed using fluorescence in situ hybridization
      (FISH) and direct sequencing. RESULTS: Unsupervised analysis of gene expression
      profiles partitioned medulloblastomas into five distinct subgroups (subgroups A
      to E). Gene expression signatures that distinguished these subgroups predicted
      the presence of key molecular alterations that we subsequently confirmed by gene
      sequence analysis and FISH. Subgroup-specific abnormalities included mutations in
      the Wingless (WNT) pathway and deletion of chromosome 6 (subgroup B) and
      mutations in the Sonic Hedgehog (SHH) pathway (subgroup D). Real-time RT-PCR
      analysis of gene expression profiles was then used to predict accurately the
      presence of mutations in the WNT and SHH pathways in a separate group of 31
      medulloblastomas. CONCLUSION: Genome-wide expression profiles can partition large
      tumor cohorts into subgroups that are enriched for specific genetic alterations.
      This approach may assist ultimately in the selection of patients for future
      clinical trials of molecular targeted therapies.

PMID- 16567769
TI  - Prospective evaluation of the relationship of patient age and paclitaxel clinical
      pharmacology: Cancer and Leukemia Group B (CALGB 9762).
AB  - PURPOSE: To prospectively evaluate the pharmacokinetics and toxicity profile of
      paclitaxel in relation to patient age in adults > or = 55 years old. PATIENTS AND
      METHODS: Paclitaxel was administered at 175 mg/m2 for 3 hours to 153 patients, 46
      of whom were > or = 75 years of age. Pharmacokinetic and toxicity assessments
      were performed. Data were analyzed by cohort (cohort 1, age 55 to 64 years;
      cohort 2, age 65 to 74 years; cohort 3, age > or = 75 years). RESULTS: Paclitaxel
      concentration versus time (AUC) and total-body clearance (CL(tb)) data were
      available for 122 patients (cohort 1, 46 patients; cohort 2, 44 patients; cohort
      3, 32 patients). Mean paclitaxel AUC increased across cohorts (P = .01). Mean
      (SE) AUCs were 22.4 (2.5) micromol/L x hour, 26.2 (2.8) micromol/L x hour, and
      31.7 (5.6) micromol/L x hour for cohorts 1, 2, and 3, respectively. There was a
      corresponding significant (P = .007) age-related decrease in mean (SE) paclitaxel
      CL(tb) (cohort 1, 11.0 [0.7] L/h/m2; cohort 2, 9.3 [0.6] L/h/m2; cohort 3, 8.2
      [0.6] L/h/m2). Patients in cohort 3 experienced significantly lower absolute
      neutrophil count nadirs than did younger groups (P = .02). There was also a
      significant increase in percentage of patients with > or = grade 3 neutropenia
      across age cohorts (cohort 1, 22%; cohort 2, 35%; cohort 3, 49%; P = .006).
      However, the increased exposure of patients to paclitaxel and increased
      neutropenia were not reflected in adverse clinical sequelae such as
      hospitalization for toxicity (P = .82), receiving intravenous antibiotics (P =
      .21), or experiencing a temperature more than 38 degrees C (P = .45). CONCLUSION:
      Although paclitaxel CL(tb) decreases with increasing patient age, there is great
      interpatient variability. Cooperative group studies to evaluate the effect of
      aging on pharmacokinetics are feasible.

PMID- 16567770
TI  - Endogenous steroid hormone concentrations and risk of breast cancer: does the
      association vary by a woman's predicted breast cancer risk?
AB  - PURPOSE: To examine whether the associations of endogenous estrogens and
      testosterone with breast cancer risk differ between high- and low-risk women, as
      determined by the Gail model and the Rosner and Colditz model, and by family
      history of breast cancer. METHODS: We conducted a prospective nested case-control
      study within the Nurses' Health Study. From 1989 or 1990 until June 2000, blood
      samples were collected, 418 breast cancer patient cases were identified, and two
      controls (total n = 817) were matched to each case. We classified women as high
      or low risk based on their family history of breast cancer, their 5-year Gail
      risk score, and their 5-year Rosner and Colditz risk score. Multivariate relative
      risks (RR) and 95% CI were calculated by unconditional logistic regression,
      adjusting for matching and breast cancer risk factors. RESULTS: Estrone sulfate
      was statistically significantly associated with breast cancer risk among women
      with low (< 1.66%) and high (> or = 2.52%; 75th percentile) Gail predicted risk
      (fourth v first quartile RR = 3.6; 95% CI, 1.9 to 7.0; RR = 2.5; 95% CI, 1.2 to
      5.1, respectively). Testosterone results were similar across strata of predicted
      risk, with two times the risk in the fourth (v first) quartile. Estradiol
      appeared more strongly associated with breast cancer in women with higher
      predicted risk (RR = 4.5; 95% CI, 2.1 to 9.5) compared with women with lower risk
      (RR = 2.1; 95% CI, 1.2 to 3.6), but differences were not statistically
      significant. Results were similar across predicted Rosner and Colditz risk
      scores. CONCLUSION: These data suggest that higher levels of endogenous estrogens
      and testosterone are associated with increased breast cancer risk, regardless of
      predicted risk or family history of breast cancer.

PMID- 16567771
TI  - Micrometastases in sentinel lymph node in a multicentric study: predictive
      factors of nonsentinel lymph node involvement--Groupe des Chirurgiens de la
      Federation des Centres de Lutte Contre le Cancer.
AB  - PURPOSE: To determine the rate of nonsentinel lymph node (NSN) involvement at
      axillary lymph node dissection (ALND) and predictive factors of this involvement
      following detection of micrometastasis in sentinel nodes (SN). METHODS: We
      analyzed 700 observations of SN micrometastases with additional ALND with the
      characteristics of the patients, tumors, and SN. RESULTS: Involvement of SN was
      diagnosed 388 times by serial sections (55.4%) with standard hemoxylin and eosin
      staining (HES) and 312 times solely on immunohistochemical analysis (IHC; 44.6%).
      The accurate size of the micrometastases was indicated in 488 cases: 301 larger
      than 0.2 mm (61.7%) and 187 < or = 0.2 mm (38.3%). Ninety-four patients (13.4%)
      presented an NSN involvement with only one NSN involved in 62 cases (66%).
      Predictive factors of NSN involvement were in univariate analysis (pT stage [P <
      .000], menopausal status [P = .048], T stage [P = .006], grade [P = .013],
      lymphovascular invasion [LVI; P = .013], histologic tumor type [P = .017], and
      method of micrometastasis detection, by HES or IHC [P = .015]) and in
      multivariate analysis (pT stage < or = or > 20 mm [odds ratio, 2.54],
      micrometastases detected by HES or IHC [odds ratio,1.734], presence or absence of
      LVI [odds ratio, 1.706]). Micrometastasis size < or = or greater than 0.2 mm was
      not predictive. CONCLUSION: This study confirms the value of serial sections and
      the vital role played by IHC in screening for small micrometastases. Omission of
      additional ALND may be envisaged with minimal risk for pT1a and pT1b tumors, and
      pT1a-b-c tumors corresponding to tubular, colloidal, or medullar cancers.

PMID- 16567772
TI  - Traditional versus up-front [18F] fluorodeoxyglucose-positron emission tomography
      staging of non-small-cell lung cancer: a Dutch cooperative randomized study.
AB  - PURPOSE: We investigated whether application of positron emission tomography
      (PET) immediately after first presentation might simplify staging while
      maintaining accuracy, as compared with traditional strategy in routine clinical
      setting. METHODS: At first presentation, patients with a provisional diagnosis of
      lung cancer without overt dissemination were randomly assigned to traditional
      work-up (TWU) according to international guidelines or early PET followed by
      histologic/cytologic verification of lesions, or imaging and follow-up. Patients
      with [18F] fluorodeoxyglucose (18FDG) -avid, noncentral tumors without suspicion
      of mediastinal or distant metastases on PET proceeded directly to thoracotomy.
      Follow-up in presumed benign lesions was at least 12 months. In patients treated
      with surgery or neoadjuvant therapy, the quality of staging was measured by
      comparing the clinical stage to the final stage (combination of peroperative
      staging and 6 months of follow-up). To investigate test substitution, we analyzed
      the number of (non)invasive tests to achieve clinical TNM staging, and its
      associated costs. RESULTS: Between 1999 and 2001, 465 patients (233 TWU, 232 PET)
      were enrolled at 22 hospitals. The mean (standard deviation) number of procedures
      to finalize staging was equal in the TWU arm and the PET arm: 7.9 (2.0) v 7.9
      (1.9), P = .90, respectively. Mediastinoscopies occurred significantly less often
      in the PET arm. Agreement between clinical and final stage was good in both arms
      (kappa = .85 v .78; P = .07). Costs did not differ significantly. CONCLUSION: Up
      front 18FDG-PET in patients with (suspected) lung cancer does not reduce the
      overall number of diagnostic test, but it maintains quality of TNM staging with
      the use of less invasive surgery.

PMID- 16567773
TI  - Growing bone and cartilage. The role of mesenchymal stem cells.

PMID- 16567774
TI  - An unstable pelvic ring. The killing fracture.

PMID- 16567775
TI  - Current concepts in the management of metastatic spinal disease. The role of
      minimally-invasive approaches.

PMID- 16567776
TI  - The effect of the diameter of metal-on-metal bearings on systemic exposure to
      cobalt and chromium.
AB  - The recent resurgence in the use of metal-on-metal bearings has led to fresh
      concerns over metal wear and elevated systemic levels of metal ions. In order to
      establish if bearing diameter influences the release of metal ions, we compared
      the whole blood levels of cobalt and chromium (at one year) and the urinary
      cobalt and chromium output (at one to three and four to six years) following
      either a 50 mm or 54 mm Birmingham hip resurfacing or a 28 mm Metasul total hip
      replacement. The whole blood concentrations and daily output of cobalt and
      chromium in these time periods for both bearings were in the same range and
      without significant difference.

PMID- 16567777
TI  - The association between metal ions from hip resurfacing and reduced T-cell
      counts.
AB  - We have studied the relationship between metal ion levels and lymphocyte counts
      in patients with metal-on-metal hip resurfacings. Peripheral blood samples were
      analysed for lymphocyte subtypes and whole blood cobalt and chromium ion levels
      in 68 patients (34 with metal-on-metal hip resurfacings and 34 with standard
      metal-on-polyethylene total hip replacements). All hip components were
      radiologically well-fixed and the patients were asymptomatic. Cobalt and chromium
      levels were significantly elevated in the patients with metal-on-metal hip
      resurfacings, compared with the patients with standard metal-on-polyethylene
      designs (p < 0.0001). There was a statistically significant decrease in the level
      of CD8(+) cells (T-cytotoxic/suppressor) (p = 0.005) in the metal-on-metal hip
      resurfacing group. A threshold level of blood cobalt and chromium ions was
      associated with reduced CD8(+) T-cell counts. We have no evidence that our
      patients suffered as a result of this reduced level of CD8(+) T-cells.

PMID- 16567778
TI  - Bone remodelling around a cemented polyethylene cup. A longitudinal densitometry
      study.
AB  - The aims of this study were to examine the repeatability of measurements of bone
      mineral density (BMD) around a cemented polyethylene Charnley acetabular
      component using dual-energy x-ray absorptiometry and to determine the
      longitudinal pattern of change in BMD during the first 24 months after surgery.
      The precision of measurements of BMD in 19 subjects ranged from 7.7% to 10.8%
      between regions, using a four-region-of-interest model. A longitudinal study of
      27 patients demonstrated a transient decrease in net pelvic BMD during the first
      12 months, which recovered to baseline at 24 months. The BMD in the region medial
      to the dome of the component reduced by between 7% and 10% during the first three
      months, but recovered to approximately baseline values by two years. Changes in
      BMD in the pelvis around cemented acetabular components may be measured using
      dual-energy x-ray absorptiometry. Bone loss after insertion of a cemented
      Charnley acetabular component is small, transient and occurs mainly at the medial
      wall of the acetabulum. After two years, bone mass returns to baseline values,
      with a pattern suggesting a uniform transmission of load to the acetabulum.

PMID- 16567779
TI  - Treatment of avascular necrosis of the hip by a non-vascularised cortical graft.
AB  - This retrospective study describes the long-term results of core decompression
      and placement of a non-vascularised bone graft in the management of avascular
      necrosis of the femoral head. We treated 80 hips in 65 patients, 18 by a cortical
      tibial autograft and 62 by a fibular allograft. The mean age of the patients was
      36 years (SD 13.2). A total of 78 hips were available for evaluation of which pre
      operatively six were Ficat-Arlet stage 0, three stage I, 31 stage IIA, 16 stage
      IIB, 13 stage III and nine stage IV. A total of 34 hips (44%) were revised at a
      mean of four years (SD 3.8). Survivorship analysis using a clinical end-point
      showed a survival rate of 59% five years after surgery. We found a significant
      difference (p = 0.002) in survivorship, when using a clinical and radiological
      end-point, between the two grafts, in favour of the tibial autograft. We
      considered this difference to be the result of the better quality and increased
      volume of tibial bone compared with that from the trochanteric region used with
      the fibular allograft. This is a relatively simple, extra-articular and
      reproducible procedure. In our view core decompression, removal of the necrotic
      tissue and packing of the cancellous grafts into the core track are vital parts
      of the procedure.

PMID- 16567780
TI  - Peri-prosthetic bone density after implantation of a custom-made femoral
      component. A five-year follow-up.
AB  - Peri-prosthetic bone loss caused by stress shielding may be associated with
      aseptic loosening of femoral components. In order to increase primary stability
      and to reduce stress shielding, a three-dimensional, cementless individual
      femoral (Evolution K) component was manufactured using pre-operative CT scans.
      Using dual energy x-ray absorptiometry, peri-prosthetic bone density was measured
      in 43 patients, three months, six months, 3.6 and 4.6 years after surgery. At
      final follow-up there was a significant reduction in mean bone density in the
      proximal Gruen zones of -30.3% (zone 7) and -22.8% (zone 1). The density in the
      other zones declined by a mean of between -4% and -16%. We conclude that the
      manufacture of a three-dimensional, custom-made femoral component could not
      prevent a reduction in peri-prosthetic bone density.

PMID- 16567781
TI  - Differences in ion release after ceramic-on-ceramic and metal-on-metal total hip
      replacement. Medium-term follow-up.
AB  - Modern metal-on-metal bearings produce less wear debris and osteolysis, but have
      the potential adverse effect of release of ions. Improved ceramic-on-ceramic
      bearings have the lowest wear of all, but the corrosion process has not been
      analysed. Our aim was to measure the serum ion release (ng/ml) in 23 patients
      having stable hip prostheses with a ceramic-on-ceramic coupling (group A) and to
      compare it with the release in 42 patients with a metal-on-metal bearing (group
      B) in the medium term. Reference values were obtained from a population of 47
      healthy subjects (group C). The concentrations of chromium, cobalt, aluminium and
      titanium were measured. There was a significant increase of cobalt, chromium and
      aluminium levels (p < 0.05) in group B compared with groups A and C. Group A did
      not differ significantly from the control group. Despite the apparent advantage
      of a metal-on-metal coupling, especially in younger patients with a long life
      expectancy, a major concern arises regarding the extent and duration of ion
      exposure. For this reason, the low corrosion level in a ceramic-on-ceramic
      coupling could be advantageous.

PMID- 16567782
TI  - Decrease in anterior knee laxity by electrical stimulation of normal and
      reconstructed anterior cruciate ligaments.
AB  - We have investigated the changes in anterior laxity of the knee in response to
      direct electrical stimulation of eight normal and 45 reconstructed anterior
      cruciate ligaments (ACLs). In the latter, the mean time from reconstruction was
      26.7 months (24 to 32). The ACL was stimulated electrically using a bipolar
      electrode probe during arthroscopy. Anterior laxity was examined with the knee
      flexed at 20 degrees under a force of 134 N applied anteriorly to the tibia using
      the KT-2000 knee arthrometer before, during and after electrical stimulation.
      Anterior tibial translation in eight normal and 17 ACL-reconstructed knees was
      significantly decreased during stimulation, compared with that before
      stimulation. In 28 knees with reconstruction of the ACL, in 22 of which the
      grafts were found to have detectable somatosensory evoked potentials during
      stimulation, anterior tibial translation was not decreased. These findings
      suggest that the ACL-hamstring reflex arc in normal knees may contribute to the
      functional stability and that this may not be fully restored after some
      reconstructions of the ACL.

PMID- 16567783
TI  - Interobserver variation in the measurement of patellar height after total knee
      arthroplasty.
AB  - We assessed the reproducibility and accuracy of four ratios used to measure
      patellar height, namely the Blackburne-Peel, Caton-Deschamps, Insall-Salvati and
      modified Insall-Salvati, before and after total knee arthroplasty. The patellar
      height was measured, by means of the four ratios, on the pre- and post-operative
      lateral radiographs of 44 patients (45 knees) who had undergone total knee
      arthroplasty. Two independent observers measured the films sequentially, in
      identical conditions, totalling 720 measurements per observer. Statistical
      analysis, comparing both observers and ratios, was carried out using the
      intraclass correlation coefficient. Before operation there was greater
      interobserver variation using either the Insall-Salvati or modified Insall
      Salvati ratios than when using the Caton-Deschamps or Blackburne-Peel methods.
      This was because of difficulty in identifying the insertion of the patellar
      tendon. Before operation, there was a minimal difference in reliability between
      these methods. After operation the interobserver difference was greatly reduced
      using both the Caton-Deschamps and Blackburne-Peel methods, which use the
      prosthetic joint line, compared with the Insall-Salvati and modified Insall
      Salvati, which reference from the insertion of the patellar tendon. The
      theoretical advantage of using the Insall-Salvati and modified Insall-Salvati
      ratios in measuring true patellar height after total knee arthroplasty needs to
      be balanced against their significant interobserver variability and inferior
      reliability when compared with other ratios.

PMID- 16567784
TI  - Pathology of the torn rotator cuff tendon. Reduction in potential for repair as
      tear size increases.
AB  - We have studied cellular and vascular changes in different stages of full
      thickness tears of the rotator cuff. We examined biopsies from the supraspinatus
      tendon in 40 patients with chronic rotator cuff tears who were undergoing surgery
      and compared them with biopsies from four uninjured subscapularis tendons.
      Morphological and immunocytochemical methods using monoclonal antibodies directed
      against leucocytes, macrophages, mast cells, proliferative and vascular markers
      were used. Histological changes indicative of repair and inflammation were most
      evident in small sized rotator cuff tears with increased fibroblast cellularity
      and intimal hyperplasia, together with increased expression of leucocyte and
      vascular markers. These reparative and inflammatory changes diminished as the
      size of the rotator cuff tear increased. Marked oedema and degeneration was seen
      in large and massive tears, which more often showed chondroid metaplasia and
      amyloid deposition. There was no association between the age of the patient and
      the duration of symptoms. In contrast, large and massive tears showed no increase
      in the number of inflammatory cells and blood vessels. Small sized rotator cuff
      tears retained the greatest potential to heal, showing increased fibroblast
      cellularity, blood vessel proliferation and the presence of a significant
      inflammatory component. Tissue from large and massive tears is of such a
      degenerative nature that it may be a significant cause of re-rupture after
      surgical repair and could make healing improbable in this group.

PMID- 16567785
TI  - The results of arthroplasty in osteoarthritis of the shoulder.
AB  - We have undertaken a prospective clinical and radiological analysis of 124
      shoulder arthroplasties (113 patients) carried out for osteoarthritis. The
      clinical results showed improvement in the absolute Constant score and the
      American Shoulder and Elbow Surgeons score of 22 and 43, respectively. Both were
      statistically significant (p < 0.001). There was no significant difference in the
      scores after hemiarthroplasty and total arthroplasty in those patients with an
      intact rotator cuff. When revision was used as the end-point for survival at ten
      years, survival of 86%, or 90% if glenoid components made of Hylamer sterilised
      in air were omitted, was obtained in primary osteoarthritis. The most common
      cause for revision in the hemiarthroplasty group was glenoid pain at a mean of
      1.5 years; in the total arthroplasty group it was loosening of the glenoid at a
      mean of 4.5 years. Analysis of pre-operative factors showed that the risk of
      gross loosening of the glenoid increased threefold when there was evidence of
      erosion of the glenoid at operation. Shoulder arthroplasty should not be delayed
      once symptomatic osteoarthritis has been established and should be undertaken
      before failure of the cuff or erosion of the glenoid are present.

PMID- 16567786
TI  - Treatment of anterior fracture-dislocations of the proximal humerus by open
      reduction and internal fixation.
AB  - Over a seven-year period we treated a consecutive series of 58 patients, 20 men
      and 38 women with a mean age of 66 years (21 to 87) who had an acute complex
      anterior fracture-dislocation of the proximal humerus. Two patterns of injury are
      proposed for study based upon a prospective assessment of the pattern of soft
      tissue and bony injury and the degree of devascularisation of the humeral head.
      In 23 patients, the head had retained capsular attachments and arterial back
      bleeding (type-I injury), whereas in 35 patients the head was devoid of
      significant soft-tissue attachments with no active arterial bleeding (type-II
      injury). Following treatment by open reduction and internal fixation, only two of
      23 patients with type-I injuries developed radiological evidence of osteonecrosis
      of the humeral head, compared with four of seven patients with type-II injuries.
      A policy of primary treatment by open reduction and internal fixation of type-I
      injuries is justified, whereas most elderly patients (aged 60 years or over) with
      type-II injuries are best treated by hemiarthroplasty. The best treatment for
      younger patients (aged under 60 years) who sustain type-II injuries is
      controversial and an individualised approach to their management is advocated.

PMID- 16567787
TI  - Total elbow arthroplasty with the Coonrad/Coonrad-Morrey prosthesis. A 10- to 31
      year survival analysis.
AB  - There have been few reports in the literature of total elbow arthroplasty
      extending beyond 10 to 15 years. We reviewed 40 patients (41 elbows) with a mean
      age of 56 years (19 to 83) who had undergone a Coonrad/Coonrad-Morrey elbow
      arthroplasty by one surgeon for various diagnoses between 1974 and 1994. Surgical
      selection excluded patients with previous elbow infection or who refused to
      accept a sedentary level of elbow activity postoperatively. Objective data were
      collected from charts, radiographs, clinical photographs and supplemented by the
      referring orthopaedic surgeons' records and radiographs if health or distance
      prevented a patient from returning for final review. Subjective outcome was
      defined by patient satisfaction. Of the 41 elbows, 21 were functional between 10
      and 14 years after operation, ten between 15 and 19 years and ten between 20 and
      31 years. There were 14 complications and 13 revisions, but no cases of acute
      infection, or permanent removal of any implant.

PMID- 16567789
TI  - The influence of facet tropism on herniation of the lumbar disc in adolescents
      and adults.
AB  - We carried out a study to determine the effect of facet tropism on the
      development of adolescent and adult herniation of the lumbar disc. We assessed
      149 levels in 140 adolescents aged between 13 and 18 years and 119 levels in 111
      adults aged between 40 and 49 years with herniation. The facet tropism of each
      patient was measured at the level of the herniated disc by CT. There was no
      significant difference in facet tropism between the herniated and the normal
      discs in both the adolescent and adult groups, except at the L4-L5 level in the
      adults. Facet tropism did not influence the development of herniation of the
      lumbar disc in either adolescents or adults.

PMID- 16567788
TI  - Spinal and pelvic parameters in Marfan's syndrome and their relevance to surgical
      planning.
AB  - Spinal deformities are a common feature of Marfan's syndrome and can be a
      significant cause of morbidity. The morphology of the scoliosis associated with
      this condition was previously described by Sponseller, but no correlation with
      the pelvic parameters has been seen. We performed a retrospective radiological
      study of 58 patients with scoliosis, secondary to Marfan's syndrome and related
      the findings in the thoracolumbar spine to the pelvic parameters, including
      pelvic version (tilt), pelvic incidence and sacral slope. Our results showed
      marked abnormalities in the pelvic values compared with those found in the
      unaffected population, with increased retroversion of the pelvis in particular.
      In addition we found a close correlation between the different patterns of pelvic
      parameters and scoliosis morphology. We found that pelvic abnormalities may
      partially dictate the spinal disorders seen in Marfan's syndrome. Our results
      supplement the well-established Sponseller classification, as well as stressing
      the importance of considering the orientation of the pelvis when planning
      surgery.

PMID- 16567790
TI  - Does the disabilities of the arm, shoulder and hand (DASH) scoring system only
      measure disability due to injuries to the upper limb?
AB  - Although the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was
      designed, and has been validated, as a measure of disability in patients with
      disorders of the upper limb, the influence of those of the lower limb on
      disability as measured by the DASH score has not been assessed. The aim of this
      study was to investigate whether it exclusively measures disability associated
      with injuries to the upper limb. The Short Musculoskeletal Functional Assessment,
      a general musculoskeletal assessment instrument, was also completed by
      participants. Disability was compared in 206 participants, 84 with an injury to
      the upper limb, 73 with injury to the lower limb and 49 controls. We found that
      the DASH score also measured disability in patients with injuries to the lower
      limb. Care must therefore be taken when attributing disability measured by the
      DASH score to injuries of the upper limb when problems are also present in the
      lower limb. Its inability to discriminate clearly between disability due to
      problems at these separate sites must be taken into account when using this
      instrument in clinical practice or research.

PMID- 16567791
TI  - Delay increases the need for open reduction of type-III supracondylar fractures
      of the humerus.
AB  - Recent reports have suggested that a delay in the management of type-III
      supracondylar fractures of the humerus does not affect the outcome. In this
      retrospective study we examined whether the timing of surgery affected peri
      operative complications, or the need for open reduction. There were 171 children
      with a closed type-III supracondylar fracture of the humerus and no vascular
      compromise in our study. They were divided into two groups: those treated less
      than eight hours from presentation to the Accident and Emergency Department (126
      children), and those treated more than eight hours from presentation (45
      children). There were no differences in the rate of complications between the
      groups, but children waiting more than eight hours for reduction were more likely
      to undergo an open reduction (33.3% vs 11.2%, p < 0.05) and there was a weak
      correlation (p = 0.062) between delay in surgery and length of operating time.
      Consequently, we would still recommend treating these injuries at the earliest
      opportunity.

PMID- 16567793
TI  - Flexible intramedullary nails for unstable fractures of the tibia in children. An
      eight-year experience.
AB  - Flexible intramedullary nailing is gaining popularity as an effective method of
      treating long-bone fractures in children. We retrospectively reviewed the records
      and radiographs of 56 unstable fractures of the tibia in 54 children treated
      between March 1997 and May 2005. All were followed up for at least two months
      after the removal of the nails. Of the 56 tibial fractures, 13 were open. There
      were no nonunions. The mean time to clinical and radiological union was ten
      weeks. Complications included residual angulation of the tibia, leg-length
      discrepancy, deep infection and failures of fixation. All achieved an excellent
      functional outcome. We conclude that flexible intramedullary fixation is an easy
      and effective method of management of both open and closed unstable fractures of
      the tibia in children.

PMID- 16567792
TI  - Treatment of local recurrences of giant cell tumour in long bones after curettage
      and cementing. A Scandinavian Sarcoma Group study.
AB  - We retrospectively studied local recurrence of giant cell tumour in long bones
      following treatment with curettage and cementing in 137 patients. The median
      follow-up time was 60 months (3 to 166). A total of 19 patients (14%) had at
      least one local recurrence, the first was diagnosed at a median of 17 months (3
      to 29) after treatment of the primary tumour. There were 13 patients with a total
      of 15 local recurrences who were successfully treated by further curettage and
      cementing. Two patients with a second local recurrence were consequently treated
      twice. At the last follow-up, at a median of 53 months (3 to 128) after the most
      recent operation, all patients were free from disease and had good function. We
      concluded that local recurrence of giant cell tumour after curettage and
      cementing in long bones can generally be successfully treated with further
      curettage and cementing, with only a minor risk of increased morbidity. This
      suggests that more extensive surgery for the primary tumour in an attempt to
      obtain wide margins is not the method of choice, since it leaves the patient with
      higher morbidity with no significant gain with respect to cure of the disease.

PMID- 16567794
TI  - Can pre-operative skin marking transfer methicillin-resistant Staphylococcus
      aureus between patients? A laboratory experiment.
AB  - National guidelines state that in patients undergoing operations the site of the
      procedure should be marked. In clinical practice the same marker is used
      repeatedly. We are not aware of any investigation regarding the theoretical risk
      of transferring organisms such as methicillin-resistant Staphyloccocus aureus
      (MRSA) between patients by a skin marker. In an experimental setting, Penflex and
      Viomedex skin markers were tested 30 times each after contaminating them with a
      standard inoculum of MRSA. The survival of the organism on the tip of the markers
      was assessed by culture on MRSA-indicator nutrient agar plates at 0, 5, 15 and 60
      minutes, 24 and 48 hours and at 1, 2, and 3 weeks after contamination. There was
      a significant difference between the markers, with the Penflex showing no
      survival of MRSA after 15 minutes whereas the Viomedex product continued to
      produce MRSA cultures for up to three weeks.

PMID- 16567795
TI  - The culture of articular chondrocytes in hydrogel constructs within a bioreactor
      enhances cell proliferation and matrix synthesis.
AB  - Bovine and human articular chondrocytes were seeded in 2% alginate constructs and
      cultured for up to 19 days in a rotating-wall-vessel (RWV) and under static
      conditions. Culture within the RWV enhanced DNA levels for bovine chondrocyte
      seeded constructs when compared with static conditions but did not produce
      enhancement for human cells. There was a significant enhancement of
      glycosaminoglycans and hydroxyproline synthesis for both bovine and human
      chondrocytes. In all cases, histological analysis revealed enhanced Safranin-O
      staining in the peripheral regions of the constructs compared with the central
      region. There was an overall increase in staining intensity after culture within
      the RWV compared with static conditions. Type-II collagen was produced by both
      bovine and human chondrocytes in the peripheral and central regions of the
      constructs and the staining intensity was enhanced by culture within the RWV. A
      capsule of flattened cells containing type-I collagen developed around the
      constructs maintained under static conditions when seeded with either bovine or
      human chondrocytes, but not when cultured within the RWV bioreactor.

PMID- 16567796
TI  - Sympathetic afferent units from lumbar intervertebral discs.
AB  - To clarify the pathomechanisms of discogenic low back pain, the sympathetic
      afferent discharge originating from the L5-L6 disc via the L2 root were
      investigated neurophysiologically in 31 Lewis rats. Sympathetic afferent units
      were recorded from the L2 root connected to the lumbar sympathetic trunk by rami
      communicantes. The L5-L6 discs were mechanically probed, stimulated electrically
      to evoke action potentials and, finally, treated with chemicals to produce an
      inflammatory reaction. We could not obtain a response from any units in the L5-L6
      discs using mechanical stimulation, but with electrical stimulation we identified
      42 units consisting mostly of A-delta fibres. In some experiments a response to
      mechanical probing of the L5-L6 disc was recognised after producing an
      inflammatory reaction. This study suggests that mechanical stimulation of the
      lumbar discs may not always produce pain, whereas inflammatory changes may cause
      the disc to become sensitive to mechanical stimuli, resulting in nociceptive
      information being transmitted as discogenic low back pain to the spinal cord
      through the lumbar sympathetic trunk. This may partly explain the variation in
      human symptoms of degenerate discs.

PMID- 16567797
TI  - The care of pin sites with external fixation.

PMID- 16567798
TI  - Brachial plexus palsy secondary to birth injuries.

PMID- 16567799
TI  - BRCA1 modulates xenobiotic stress-inducible gene expression by interacting with
      ARNT in human breast cancer cells.
AB  - Previously, we have reported that BRCA1 regulates the expression of various
      classes of genes, including genes involved in xenobiotic stress responses (Bae,
      I., Fan, S., Meng, Q., Rih, J. K., Kim, H. J., Kang, H. J., Xu, J., Goldberg, I.
      D., Jaiswal, A. K., and Rosen, E. M. (2004) Cancer Res. 64, 7893-7909). In the
      present study, we have investigated the effects of BRCA1 on xenobiotic stress
      inducible gene expression. In response to aryl hydrocarbon receptor (AhR)
      ligands, cytoplasmic AhR becomes activated and then translocates to the nucleus
      where it forms a complex with the aryl hydrocarbon receptor nuclear translocator
      (ARNT). Subsequently, the AhR.ARNT complex binds to the enhancer or promoter of
      genes containing a xenobiotic stress-responsive element and regulates the
      expression of multiple target genes including cytochrome P450 subfamily
      polypeptide 1 (CYP1A1). In this study, we have found that endogenous and
      overexpressed exogenous wild-type BRCA1 affect xenobiotic stress-induced CYP1A1
      gene expression. Using a standard chromatin immunoprecipitation assay, we have
      demonstrated that BRCA1 is recruited to the promoter regions of CYP1A1 and CYP1B1
      along with ARNT and/or AhR following xenobiotic exposure. Our findings suggest
      that BRCA1 may be physiologically important for mounting a normal response to
      xenobiotic insults and that it may function as a coactivator for ARNT activity.
      Using immunoprecipitation, Western blotting, and glutathione S-transferase
      capture assays, a xenobiotic-independent interaction between BRCA1 and ARNT has
      been identified, although it is not yet known whether this is a direct or
      indirect interaction. We have also found that the inducibility of CYP1A1 and
      CYP1B1 transcripts following xenobiotic stress was significantly attenuated in
      BRCA1 knockdown cells. This reduced inducibility is associated with an altered
      stability of ARNT and was almost completely reversed in cells transfected with an
      ARNT expression vector. Finally, we have found that xenobiotic (TCDD) treatments
      of breast cancer cells containing reduced levels of BRCA1 cause the transcription
      factor ARNT to become unstable.

PMID- 16567800
TI  - Molecular basis of formaldehyde detoxification. Characterization of two S
      formylglutathione hydrolases from Escherichia coli, FrmB and YeiG.
AB  - The Escherichia coli genes frmB (yaiM) and yeiG encode two uncharacterized
      proteins that share 54% sequence identity and contain a serine esterase motif. We
      demonstrated that purified FrmB and YeiG have high carboxylesterase activity
      against the model substrates, p-nitrophenyl esters of fatty acids (C2-C6) and
      alpha-naphthyl acetate. However, both proteins had the highest hydrolytic
      activity toward S-formylglutathione, an intermediate of the glutathione-dependent
      pathway of formaldehyde detoxification. With this substrate, both proteins had
      similar affinity (Km = 0.41-0.43 mM), but FrmB was almost 5 times more active.
      Alanine replacement mutagenesis of YeiG demonstrated that Ser145, Asp233, and
      His256 are absolutely required for activity, indicating that these residues
      represent a serine hydrolase catalytic triad in this protein and in other S
      formylglutathione hydrolases. This was confirmed by inspecting the crystal
      structure of the Saccharomyces cerevisiae S-formylglutathione hydrolase YJG8
      (Protein Data Bank code 1pv1), which has 45% sequence identity to YeiG. The
      structure revealed a canonical alpha/beta-hydrolase fold and a classical serine
      hydrolase catalytic triad (Ser161, His276, Asp241). In E. coli cells, the
      expression of frmB was stimulated 45-75 times by the addition of formaldehyde to
      the growth medium, whereas YeiG was found to be a constitutive enzyme. The
      simultaneous deletion of both frmB and yeiG genes was required to increase the
      sensitivity of the growth of E. coli cells to formaldehyde, suggesting that both
      FrmB and YeiG contribute to the detoxification of formaldehyde. Thus, FrmB and
      YeiG are S-formylglutathione hydrolases with a Ser-His-Asp catalytic triad
      involved in the detoxification of formaldehyde in E. coli.

PMID- 16567801
TI  - Distinct glycan structures of uroplakins Ia and Ib: structural basis for the
      selective binding of FimH adhesin to uroplakin Ia.
AB  - Although it has been shown that mouse uroplakin (UP) Ia, a major glycoprotein of
      urothelial apical surface, can serve as the receptor for the FimH lectin adhesin
      of type 1-fimbriated Escherichia coli, the organism that causes a great majority
      of urinary tract infections, the glycan structure of this native receptor was
      unknown. Using a sensitive approach that combines in-gel glycosidase and protease
      digestions, permethylation of released glycans, and mass spectrometry, we have
      elucidated for the first time the native glycoform structures of the mouse UPIa
      receptor and those of its non-binding homolog, UPIb, and have determined the
      glycosylation site occupancy. UPIa presents a high level of terminally exposed
      mannose residues (located on Man(6)GlcNAc(2) to Man(9)GlcNAc(2)) that are capable
      of specifically interacting with FimH. We have shown that this property is
      conserved not only in the mouse uroplakins but also in cattle and, even more
      importantly, in human UPIa, thus establishing the concept that UPIa is a major
      urothelial receptor in humans and other mammals for the mannose-specific FimH
      variant. In contrast, our results indicate that most terminally exposed glycans
      of mouse UPIb are non-mannose residues, thus explaining the failure of FimH to
      bind to this UPIb. In cattle, on the other hand, complex carbohydrates
      constituted only about 20% of the UPIb N-linked glycans. Human UPIa contained
      exclusively high mannose glycans, and human UPIb contained only complex glycans.
      The drastically different carbohydrate processing of the UPIa and UPIb proteins,
      two closely related members of the tetraspanin family, may reflect differences in
      their folding and masking due to their interactions with their associated
      proteins, UPII and UPIIIa, respectively. Results from this study shed light on
      the molecular pathogenesis of urinary tract infections and may aid in the design
      of glyco-mimetic inhibitors for preventing and treating this disease.

PMID- 16567802
TI  - A new model for ligand release. Role of side chain in gating the enediyne
      antibiotic.
AB  - Antitumor antibiotic chromoproteins such as neocarzinostatin involve a labile
      toxin that is tightly bound by a protective protein with very high affinity but
      must also be freed to exert its function. Contrary to the prevalent concept of
      ligand release, we established that toxin release from neocarzinostatin requires
      no major backbone conformational changes. We report, herein, that subtle changes
      in the side chains of specific amino acid residues are adequate to gate the
      release of chromophore. A recombinant wild type aponeocarzinostatin and its
      variants mutated around the opening of the chromophore binding cleft are employed
      to identify specific side chains likely to affect chromophore release.
      Preliminary, biophysical characterization of mutant apoproteins by circular
      dichroism and thermal denaturation indicate that the fundamental structural
      characteristics of wild type protein are conserved in these mutants. The
      chromophore reconstitution studies further show that all mutants are able to bind
      chromophore efficiently with similar complex structures. NMR studies on 15N
      labeled mutants also suggest the intactness of binding pocket structure. Kinetic
      studies of chromophore release monitored by time course fluorescence and
      quantitative high pressure liquid chromatography analyses show that the ligand
      release rate is significantly enhanced only in Phe78 mutants. The extent of DNA
      cleavage in vitro corresponds well to the rate of chromophore release. The
      results provide the first clear-cut indication of how toxin release can be
      controlled by a specific side chain of a carrier protein.

PMID- 16567803
TI  - Redox activation of aldose reductase in the ischemic heart.
AB  - Aldose reductase (AR) reduces cytotoxic aldehydes and glutathione conjugates of
      aldehydes derived from lipid peroxidation. Its inhibition has been shown to
      increase oxidative injury and abolish the late phase of ischemic preconditioning.
      However, the mechanisms by which ischemia regulates AR activity remain unclear.
      Herein, we report that rat hearts subjected to ischemia, in situ or ex vivo,
      display a 2-4-fold increase in AR activity. The AR activity was not further
      enhanced by reperfusion. Activation increased Vmax of the enzyme without
      affecting the Km and decreased the sensitivity of the enzyme to inhibition by
      sorbinil. Enzyme activation could be prevented by pretreating the hearts with the
      radical scavenging thiol, N-(2-mercaptoproprionyl)glycine or the superoxide
      dismutase mimetic, Tiron, or by treating homogenates with dithiothreitol. In
      vitro, the recombinant enzyme was activated upon treatment with H2O2 and the
      activated, but not the native enzyme, formed a covalent adduct with the sulfenic
      acid-specific reagent dimedone. The enzyme activity in the ischemic, but not the
      nonischemic heart homogenates was inhibited by dimedone. Separation of proteins
      from hearts subjected to coronary occlusion by two-dimensional electrophoresis
      and subsequent matrix-assisted laser desorption ionization time-of-flight/mass
      spectrometry analysis revealed the formation of sulfenic acids at Cys-298 and Cys
      303. These data indicate that reactive oxygen species formed in the ischemic
      heart activate AR by modifying its cysteine residues to sulfenic acids.

PMID- 16567804
TI  - Caspase-3 cleaves and inactivates the glutamate transporter EAAT2.
AB  - EAAT2 is a high affinity, Na+-dependent glutamate transporter with predominant
      astroglial localization. It accounts for the clearance of the bulk of glutamate
      released at central nervous system synapses and therefore has a crucial role in
      shaping glutamatergic neurotransmission and limiting excitotoxicity. Caspase-3
      activation and impairment in expression and activity of EAAT2 are two distinct
      molecular mechanisms occurring in human amyotrophic lateral sclerosis (ALS) and
      in the transgenic rodent model of the disease. Excitotoxicity caused by down
      regulation of EAAT2 is thought to be a contributing factor to motor neuron death
      in ALS. In this study, we report the novel evidence that caspase-3 cleaves EAAT2
      at a unique site located in the cytosolic C-terminal domain of the transporter, a
      finding that links excitotoxicity and activation of caspase-3 as converging
      mechanisms in the pathogenesis of ALS. Caspase-3 cleavage of EAAT2 leads to a
      drastic and selective inhibition of this transporter. Heterologous expression of
      mutant SOD1 proteins linked to the familial form of ALS leads to inhibition of
      EAAT2 through a mechanism that largely involves activation of caspase-3 and
      cleavage of the transporter. In addition, we found evidence in spinal cord
      homogenates of mutant SOD1 ALS mice of a truncated form of EAAT2, likely deriving
      from caspase-3-mediated proteolytic cleavage, which appeared concurrently to the
      loss of EAAT2 immunoreactivity and to increased expression of activated caspase
      3. Taken together, our findings suggest that caspase-3 cleavage of EAAT2 is one
      mechanism responsible for the impairment of glutamate uptake in mutant SOD1
      linked ALS.

PMID- 16567805
TI  - Distinct domains for anti- and pro-apoptotic activities of IEX-1.
AB  - IEX-1 (immediate early response gene X-1) is a stress-inducible gene. Its
      overexpression can suppress or enhance apoptosis dependent on the nature of
      stress, yet the polypeptide does not possess any of the functional domains that
      are homologous to those present in well characterized effectors or inhibitors of
      apoptosis. This study using sequence-targeting mutagenesis reveals a
      transmembrane-like integrated region of the protein to be critical for both pro
      apoptotic and anti-apoptotic functions. Substitution of the key hydrophobic
      residues with hydrophilic ones within this region impairs the capacity IEX-1 to
      positively and negatively regulate apoptosis. Mutations at N-linked glycosylation
      and phosphorylation sites or truncation of the C terminus of IEX-1 also abrogated
      its potential to promote cell survival. However, distinguished from the
      transmembrane-like domain, these mutants preserved pro-apoptotic activity of IEX
      1 fully. On the contrary, mutation of nuclear localization sequence, despite its
      importance in apoptosis, did not impede IEX-1-mediated cell survival. Strikingly,
      all the mutants that lose their anti-apoptotic ability are unable to prevent
      acute increases in production of intracellular reactive oxygen species (ROS) at
      the initial onset of apoptosis, whereas those mutants that can sustain anti-death
      function also control acute ROS production as sufficiently as wild-type IEX-1.
      These findings suggest a critical role of IEX-1 in regulation of intracellular
      ROS homeostasis, providing new insight into the mechanism underlying IEX-1
      mediated cell survival.

PMID- 16567806
TI  - Metal ion site engineering indicates a global toggle switch model for seven
      transmembrane receptor activation.
AB  - Much evidence indicates that, during activation of seven-transmembrane (7TM)
      receptors, the intracellular segments of the transmembrane helices (TMs) move
      apart with large amplitude, rigid body movements of especially TM-VI and TM-VII.
      In this study, AspIII:08 (Asp113), the anchor point for monoamine binding in TM
      III, was used as the starting point to engineer activating metal ion sites
      between the extracellular segments of the beta2-adrenergic receptor. Cu(II) and
      Zn(II) alone and in complex with aromatic chelators acted as potent (EC50
      decreased to 0.5 microm) and efficacious agonists in sites constructed between
      positions III:08 (Asp or His), VI:16 (preferentially Cys), and/or VII:06
      (preferentially Cys). In molecular models built over the backbone conformation of
      the inactive rhodopsin structure, the heavy atoms that coordinate the metal ion
      were located too far away from each other to form high affinity metal ion sites
      in both the bidentate and potential tridentate settings. This indicates that the
      residues involved in the main ligand-binding pocket will have to move closer to
      each other during receptor activation. On the basis of the distance constraints
      from these activating metal ion sites, we propose a global toggle switch
      mechanism for 7TM receptor activation in which inward movement of the
      extracellular segments of especially TM-VI and, to some extent, TM-VII is coupled
      to the well established outward movement of the intracellular segments of these
      helices. We suggest that the pivots for these vertical seesaw movements are the
      highly conserved proline bends of the involved helices.

PMID- 16567807
TI  - Interleukin-1beta enhances GABAA receptor cell-surface expression by a
      phosphatidylinositol 3-kinase/Akt pathway: relevance to sepsis-associated
      encephalopathy.
AB  - Sepsis-associated encephalopathy (SAE) is a frequent but poorly understood
      neurological complication in sepsis that negatively influences survival. Here we
      present clinical and experimental evidence that this brain dysfunction may be
      related to altered neurotransmission produced by inflammatory mediators. Compared
      with septic patients, SAE patients had higher interleukin-1beta (IL-1beta) plasma
      levels; interestingly, these levels decreased once the encephalopathy was
      resolved. A putative IL-1beta effect on type A gamma-aminobutyric acid receptors
      (GABA(A)Rs), which mediate fast synaptic transmission in most cerebral inhibitory
      synapses in mammals, was investigated in cultured hippocampal neurons and in
      Xenopus oocytes expressing native or foreign rat brain GABA(A)Rs, respectively.
      Confocal images in both cell types revealed that IL-1beta increases recruitment
      of GABA(A)Rs to the cell surface. Moreover, brief applications of IL-1beta to
      voltage-clamped oocytes yielded a delayed potentiation of the GABA-elicited
      chloride currents (I(GABA)); this effect was suppressed by IL-1ra, the natural IL
      1 receptor (IL-1RI) antagonist. Western blot analysis combined with I(GABA)
      recording and confocal images of GABA(A) Rs in oocytes showed that IL-1beta
      stimulates the IL-1RI-dependent phosphatidylinositol 3-kinase activation and the
      consequent facilitation of phospho-Akt-mediated insertion of GABA(A)Rs into the
      cell surface. The interruption of this signaling pathway by specific
      phosphatidylinositol 3-kinase or Akt inhibitors suppresses the cytokine-mediated
      effects on GABA(A)R, whereas activation of the conditionally active form of Akt1
      (myr-Akt1.ER*) with 4-hydroxytamoxifen reproduces the effects. These findings
      point to a previously unrecognized signaling pathway that connects IL-1beta with
      increased "GABAergic tone." We propose that through this mechanism IL-1beta might
      alter synaptic strength at central GABAergic synapses and so contribute to the
      cognitive dysfunction observed in SAE.

PMID- 16567808
TI  - Functions of ERp57 in the folding and assembly of major histocompatibility
      complex class I molecules.
AB  - ERp57 is a thiol oxidoreductase of the endoplasmic reticulum that appears to be
      recruited to substrates indirectly through its association with the molecular
      chaperones calnexin and calreticulin. However, its functions in living cells have
      been difficult to demonstrate. During the biogenesis of class I
      histocompatibility molecules, ERp57 has been detected in association with free
      class I heavy chains and, at a later stage, with a large complex termed the
      peptide loading complex. This implicates ERp57 in heavy chain disulfide
      formation, isomerization, or reduction as well as in the loading of peptides onto
      class I molecules. In this study, we show that ERp57 does indeed participate in
      oxidative folding of the heavy chain. Depletion of ERp57 by RNA interference
      delayed heavy chain disulfide bond formation, slowed folding of the heavy chain
      alpha(3) domain, and caused slight delays in the transport of class I molecules
      from the endoplasmic reticulum to the Golgi apparatus. In contrast, heavy chain
      beta(2)-microglobulin association kinetics were normal, suggesting that the
      interaction between heavy chain and beta(2) -microglobulin does not depend on an
      oxidized alpha(3) domain. Likewise, the peptide loading complex assembled
      properly, and peptide loading appeared normal upon depletion of ERp57. These
      studies demonstrate that ERp57 is involved in disulfide formation in vivo but do
      not support a role for ERp57 in peptide loading of class I molecules.
      Interestingly, depletion of another thiol oxidoreductase, ERp72, had no
      detectable effect on class I biogenesis, consistent with a specialized role for
      ERp57 in this process.

PMID- 16567810
TI  - Arginine-vasopressin activates the JAK-STAT pathway in vascular smooth muscle
      cells.
AB  - JAK (Janus-activated kinase)-STAT (signal transducers and activators of
      transcription) signaling is a major signal transduction pathway in mammalian
      cells. Different growth factors and cytokines were reported as activators of the
      JAK-STAT pathway in various cell types. Interestingly, arginine-vasopressin (AVP)
      was never reported as an inducer of the JAK-STAT pathway. In the present study,
      we show for the first time that AVP stimulation of vascular smooth muscle cells
      (VSMCs) induces STAT3 tyrosine and serine phosphorylation, followed by nuclear
      translocation of the phosphorylated STAT3. In addition, we found that AVP induced
      JAK2 tyrosine phosphorylation. Taken together, these results demonstrate that AVP
      activates the JAK-STAT pathway in VSMCs. Furthermore, our results indicate that
      AVP-induced STAT3 tyrosine phosphorylation requires both JAK2 and c-Src tyrosine
      kinases. The present study also implicates that extracellular signal-regulated
      kinase (ERK1/2), which are serine/threonine kinases, are the mediators of STAT3
      serine phosphorylation upon AVP stimulation. We further suggest that AVP-induced
      STAT3 serine phosphorylation negatively modulates AVP-induced STAT3 tyrosine
      phosphorylation. Finally, our results implicate a novel role for the JAK-STAT
      pathway, mediating AVP-induced VSMC hypertrophy.

PMID- 16567809
TI  - Polymorphisms in human langerin affect stability and sugar binding activity.
AB  - Langerhans cells are specialized skin dendritic cells that take up and degrade
      antigens for presentation to the immune system. Langerin, a cell surface C-type
      lectin of Langerhans cells, can be internalized and accumulates in Birbeck
      granules, subdomains of the endosomal recycling compartment that are specific to
      Langerhans cells. Langerin binds and mediates uptake and degradation of
      glycoconjugates containing mannose and related sugars. Analysis of the human
      genome has identified three single nucleotide polymorphisms that result in amino
      acid changes in the carbohydrate-recognition domain of langerin. The effects of
      the amino acid changes on the activity of langerin were examined by expressing
      each of the polymorphic forms. Expression of full-length versions of the four
      common langerin haplotypes in fibroblasts revealed that all of these forms can
      mediate endocytosis of neoglycoprotein ligands. However, sugar binding assays and
      differential scanning calorimetry performed on fragments from the extracellular
      domain showed that two of the amino acid changes reduce the affinity of the
      carbohydrate-recognition domain for mannose and decrease the stability of the
      extracellular domain. In addition, analysis of sugar binding by langerin
      containing the rare W264R mutation, previously identified in an individual
      lacking Birbeck granules, shows that this mutation abolishes sugar binding
      activity. These findings suggest that certain langerin haplotypes may differ in
      their binding to pathogens and thus might be associated with susceptibility to
      infection.

PMID- 16567811
TI  - Efficacy, tolerability, and safety of a novel once-daily extended-release
      metformin in patients with type 2 diabetes.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacy and safety of
      a novel extended-release metformin in patients with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: Adults with type 2 diabetes (newly diagnosed, treated with
      diet and exercise only, or previously treated with oral diabetic medications)
      were randomly assigned to receive one of three extended-release metformin
      treatment regimens (1,500 mg/day q.d., 1,500 mg/day twice daily, or 2,000 mg/day
      q.d.) or immediate-release metformin (1,500 mg/day twice daily) in a double-blind
      24-week trial. RESULTS: Significant decreases (P < 0.001) in mean HbA(1c) (A1C)
      levels were observed by week 12 in all treatment groups. The mean changes from
      baseline to end point in the two groups given 1,500 mg extended-release metformin
      (-0.73 and -0.74%) were not significantly different from the change in the
      immediate-release metformin group (-0.70%), whereas the 2,000-mg extended-release
      metformin group showed a greater decrease in A1C levels (-1.06%; mean difference
      [2,000 mg extended-release metformin - immediate-release metformin]: -0.36 [98.4%
      CI -0.65 to -0.06]). Rapid decreases in fasting plasma glucose levels were
      observed by week 1, which continued until week 8, and were maintained for the
      duration of the study. The overall incidence of adverse events was similar for
      all treatment groups, but fewer patients in the extended-release metformin groups
      discontinued treatment due to nausea during the initial dosing period than in the
      immediate-release metformin group. CONCLUSIONS: Once- or twice-daily extended
      release metformin was as safe and effective as twice-daily immediate-release
      metformin and provided continued glycemic control for up to 24 weeks of
      treatment.

PMID- 16567812
TI  - The Hyperglycemia: Intensive Insulin Infusion in Infarction (HI-5) study: a
      randomized controlled trial of insulin infusion therapy for myocardial
      infarction.
AB  - OBJECTIVE: There is conflicting evidence regarding the benefit of intravenous
      insulin therapy on mortality following acute myocardial infarction (AMI). The
      goal of the current study was to determine whether improved glycemic control,
      achieved through an insulin/dextrose infusion with a variable rate of insulin,
      reduces mortality among hyperglycemic patients with AMI. RESEARCH DESIGN AND
      METHODS: Subjects suffering AMI with either known diabetes or without diabetes
      but blood glucose level (BGL) > or =7.8 mmol/l were randomized to receive
      insulin/dextrose infusion therapy for at least 24 h to maintain a BGL <10 mmol/l
      or conventional therapy. RESULTS: A total of 240 subjects were recruited.
      Insulin/dextrose infusion did not reduce mortality at the inpatient stage (4.8
      vs. conventional 3.5%, P = 0.75), 3 months (7.1 vs 4.4%, P = 0.42), or 6 months
      (7.9 vs. 6.1%, P = 0.62). There was, however, a lower incidence of cardiac
      failure (12.7 vs. 22.8%, P = 0.04) and reinfarction within 3 months (2.4 vs.
      6.1%, P = 0.05). When analyzed by mean BGL achieved during the first 24 h,
      mortality was lower among subjects with a mean BGL < or =8 mmol/l, compared with
      subjects with a mean BGL >8 mmol/l (2 vs. 11% at 6 months, P = 0.02).
      CONCLUSIONS: We did not find a reduction in mortality among patients who received
      insulin/dextrose infusion therapy. However, it remains possible that tight
      glycemic control with insulin therapy following AMI improves outcomes.

PMID- 16567813
TI  - Long-term breast-feeding in women with type 1 diabetes.
AB  - OBJECTIVE: Breast-feeding may be more difficult in women with diabetes because of
      neonatal morbidity and fluctuating maternal blood glucose values. The frequency
      of long-term breast-feeding and the possible predictors for successful breast
      feeding were investigated. RESEARCH DESIGN AND METHODS: One hundred two
      consecutive women with type 1 diabetes were interviewed about breast-feeding
      using a semistructured questionnaire 5 days and 4 months after delivery. Clinical
      data were collected from the medical records. RESULTS: Five days after delivery,
      86% of the women were breast-feeding. Four months after delivery, 55 (54%) women
      were exclusively, 14 (14%) were partly, and 33 (32%) were not breast-feeding
      compared with 50, 26, and 24% in the background population (NS). Mothers
      exclusively breast-feeding at 4 months were characterized by previous experience
      with breast-feeding, a higher educational level, and vaginal delivery and
      included a high proportion of nonsmokers, whereas there were no associations with
      diabetes-related parameters such as white classes, duration of diabetes, HbA(1c),
      and insulin dose at conception. Breast-fed offspring had a significantly higher
      birth weight and gestational age and were less often receiving glucose
      intravenously compared with the remaining offspring. Independent predictors of
      exclusive breast-feeding at 4 months were previous experience with breast-feeding
      (odds ratio 6.3 [95% CI 2.4-17]) and higher educational level (7.1 [2.4-21]).
      Cessation of breast-feeding was mainly due to common nursing problems, such as
      perceived milk supply, and not related to maternal diabetes status. CONCLUSIONS:
      The majority of the women with type 1 diabetes initiated breast-feeding, and the
      prevalence of breast-feeding at 4 months was comparable to that in the background
      population. Independent predictors of exclusive breast-feeding at 4 months were
      previous experience with breast-feeding and higher educational level.

PMID- 16567814
TI  - Cereal fiber improves whole-body insulin sensitivity in overweight and obese
      women.
AB  - OBJECTIVE: Cereal fiber intake is linked to reduced risk of type 2 diabetes in
      epidemiological observations. The pathogenic background of this phenomenon is
      unknown. Based on recent findings, we hypothesized that intake of purified
      insoluble oat fiber may improve whole-body insulin sensitivity. RESEARCH DESIGN
      AND METHODS: A randomized, controlled, single-blind, cross-over study was
      performed, and 17 overweight or obese subjects with normal glucose metabolism
      were analyzed. After consumption of nine macronutrient-matched portions of fiber
      enriched bread (white bread enriched with 31.2 g insoluble fiber/day) or control
      (white bread) over a time period of 72 h, whole-body insulin sensitivity was
      assessed by euglycemic-hyperinsulinemic clamp. Energy intake was individually
      adjusted by providing standardized liquid meals. Hydrogen breath tests were
      performed to control for dietary adherence. RESULTS: When analyzing the entire
      cohort, whole-body glucose disposal was improved after fiber consumption (M value
      6.56 +/- 0.32 vs. 6.07 +/- 0.27 mg . min(-1) . kg(-1); P = 0.043). Thirteen
      subjects had increased hydrogen breath test concentrations after fiber
      consumption, indicating probable dietary adherence. Restricting analysis to these
      subjects, improvements in M value (6.85 +/- 0.34 vs. 6.06 +/- 0.32 mg . min(-1) .
      kg(-1); P = 0.003) and insulin sensitivity, expressed as M/I ratio (M value
      divided by mean serum insulin at steady state: 3.73 +/- 0.23 vs. 3.21 +/- 0.27; P
      = 0.02), after fiber consumption were more pronounced. Plasma lipids, serum
      magnesium, ghrelin, and adiponectin concentrations, as well as substrate
      utilization and body weight, were not significantly changed by fiber intake (P >
      0.15). CONCLUSIONS: Increased insoluble dietary fiber intake for 3 days
      significantly improved whole-body insulin sensitivity. These data suggest a
      potential mechanism linking cereal fiber intake and reduced risk of type 2
      diabetes.

PMID- 16567815
TI  - Low-saturated fat dietary counseling starting in infancy improves insulin
      sensitivity in 9-year-old healthy children: the Special Turku Coronary Risk
      Factor Intervention Project for Children (STRIP) study.
AB  - OBJECTIVE: Insulin resistance is promoted already in childhood by obesity and
      possibly by high-saturated fat intake. We examined the effect of infancy onset
      biannually given dietary counseling on markers of insulin resistance in healthy 9
      year-old children. RESEARCH DESIGN AND METHODS: Healthy 7-month-old infants (n =
      1,062) were randomized to the intervention (n = 540) and control (n = 522)
      groups. Each year, two individualized counseling sessions were organized to each
      intervention family. The purpose of counseling was to minimize children's
      exposure to known environmental atherosclerosis risk factors. Homeostasis model
      assessment of insulin resistance (HOMA-IR) index, serum lipids, blood pressure,
      and weight for height were determined in a random subgroup of 78 intervention
      children and 89 control children at the age of 9 years. RESULTS: Intervention
      children consumed less total and saturated fat than the control children (P =
      0.002 and < 0.0001, respectively). The HOMA-IR index was lower in intervention
      children than in control children (P = 0.020). There was a significant
      association between saturated fat intake and HOMA-IR. In multivariate analyses
      including saturated fat intake, study group, and other determinants of HOMA-IR
      (serum triglyceride concentration, weight for height, and systolic blood
      pressure), study group was, whereas saturated fat intake was not, significantly
      associated with HOMA-IR. This suggests that the beneficial effect of intervention
      on insulin sensitivity was largely, but not fully, explained by the decrease in
      saturated fat intake. CONCLUSIONS: The long-term biannual dietary intervention
      decreases the intake of total and saturated fat and has a positive effect on
      insulin resistance index in 9-year-old children.

PMID- 16567816
TI  - Hyperglycemia and diabetes in patients with schizophrenia or schizoaffective
      disorders.
AB  - OBJECTIVE: Pharmacoepidemiological studies have shown an increased prevalence of
      diabetes in patients with schizophrenia. To address this issue, we decided to
      assess glucose metabolism in a population of patients with schizophrenia or
      schizoaffective disorder. RESEARCH DESIGN AND METHODS: Oral glucose tolerance
      tests (OGTTs) were performed in 200 unselected in- and outpatients. Insulin
      sensitivity and beta-cell function were assessed using the homeostasis model
      assessment (HOMA) indexes and 30-min glucose and insulin levels. RESULTS: The
      mainly Western European (87.7%) study population had a mean age of 40.8 years,
      was 70% male, and had a mean fasting glucose of 5.1 mmol/l and a mean fasting
      insulin of 14.8 mU/l. Hyperglycemia was present in 7% of the population: 1.5%
      with impaired fasting glucose and 5.5% with impaired glucose tolerance. The
      prevalence of diabetes was 14.5%, of which 8% was previously known and 6.5% was
      newly diagnosed. Compared with a 1.5% prevalence of diabetes in the age-matched
      general Dutch population, the prevalence of identified cases was significantly
      increased in the study population. Comparable figures on the prevalence of
      hyperglycemia in the general population are not available. Insulin resistance was
      increased in the study population as a whole (HOMA of insulin resistance: 3.1
      3.5), irrespective of the use of antipsychotic medication and, if used,
      irrespective of its type (typical or atypical). No indication of beta-cell defect
      was found, whereas a nonsignificant increased insulin resistance was found with
      antipsychotic medication. CONCLUSIONS: OGTTs in 200 mainly Caucasian patients
      with schizophrenia or schizoaffective disorder, mean age 41 years, showed that 7%
      suffered from hyperglycemia and 14.5% from diabetes. The prevalence of diabetes
      was significantly increased compared with the general population. No differential
      effect of antipsychotic monotherapy in diabetogenic effects was found. Therefore,
      a modification of the consensus statement on antipsychotic drugs, obesity, and
      diabetes is proposed, i.e., measurement of fasting glucose in all patients with
      schizophrenia, irrespective of prescribed antipsychotic drug.

PMID- 16567817
TI  - Disorders of glucose metabolism in acute stroke patients: an underrecognized
      problem.
AB  - OBJECTIVE: To determine the prevalence of disturbances in glucose metabolism in
      patients with acute stroke. RESEARCH DESIGN AND METHODS: Consecutively admitted
      acute stroke patients (n = 286) were screened for glucose tolerance according to
      the standardized World Health Organization protocol in the 1st and 2nd week after
      the stroke event. In addition, we repeatedly measured fasting capillary blood
      glucose during the first 10 days. RESULTS: Measurements were not performed or
      cancelled if patients were not fully conscious or had severe dysphagia or early
      complications that made transfers to other hospitals necessary (n = 48). Of the
      remaining 238 patients, 20.2% had previously known diabetes; 16.4% were
      classified as having newly diagnosed diabetes, 23.1% as having impaired glucose
      tolerance (IGT), and 0.8% as having impaired fasting glucose; and only 19.7%
      showed normal glucose levels. Another 47 patients (19.7%) had hyperglycemic
      values only in the 1st week (transient hyperglycemia) or could not be fully
      classified due to missing data in the oral glucose tolerance test. Patients with
      diabetes compared with nondiabetic subjects had more severe strokes (National
      Institutes of Health Stroke Scale [NIHSS] on admission: 7.2 +/- 6.6 vs. 4.6 +/-
      3.1, 4.2 +/- 4.4, and 3.7 +/- 3.6 for IGT, transient hyperglycemia, and
      normoglycemia, respectively; P < 0.001), a worse outcome (modified Rankin scale 0
      1 at discharge: 40.2 vs. 54.4, 63.8, and 72.3% for IGT, transient hyperglycemia,
      and normoglycemia, respectively; P < 0.001), and a higher rate of infectious
      complications (35.6 vs. 12.3, 21.2, and 4.2% for IGT, transient hyperglycemia,
      and normoglycemia, respectively; P < 0.001). In the multivariate analysis, NIHSS
      on admission, female sex, and the occurrence of urinary tract infection were
      independently associated with newly diagnosed diabetes. CONCLUSIONS: The majority
      of acute stroke patients have disorders of glucose metabolism, and in most cases
      this fact has been unrecognized. Diabetes worsens the outcome of acute stroke.
      Therefore, in the post-acute phase, an oral glucose tolerance test should be
      recommended in all stroke patients with no prior history of diabetes.

PMID- 16567818
TI  - High risk of cardiovascular disease in patients with type 1 diabetes in the U.K.:
      a cohort study using the general practice research database.
AB  - OBJECTIVE: To estimate the absolute and relative risk of cardiovascular disease
      (CVD) in patients with type 1 diabetes in the U.K. RESEARCH DESIGN AND METHODS:
      Subjects with type 1 diabetes (n = 7,479) and five age- and sex-matched subjects
      without diabetes (n = 38,116) and free of CVD at baseline were selected from the
      General Practice Research Database (GPRD), a large primary care database
      representative of the U.K. population. Incident major CVD events, comprising
      myocardial infarction, acute coronary heart disease death, coronary
      revascularizations, or stroke, were captured for the period 1992-1999. RESULTS:
      The hazard ratio (HR) for major CVD was 3.6 (95% CI 2.9-4.5) in type 1 diabetic
      men compared with those without diabetes and 7.7 (5.5-10.7) in women. Increased
      HRs were found for acute coronary events (3.0 and 7.6 in type 1 diabetic men and
      women, respectively, versus nondiabetic subjects), coronary revascularizations
      (5.0 in men, 16.8 in women), and for stroke (3.7 in men, 4.8 in women). Type 1
      diabetic men aged 45-55 years had an absolute CVD risk similar to that of men in
      the general population 10-15 years older, with an even greater difference in
      women. CONCLUSIONS: Despite advances in care, these data show that absolute and
      relative risks of CVD remain extremely high in patients with type 1 diabetes.
      Women with type 1 diabetes continue to experience greater relative risks of CVD
      than men compared with those without diabetes.

PMID- 16567819
TI  - Diabetes and 30-day mortality from peptic ulcer bleeding and perforation: a
      Danish population-based cohort study.
AB  - OBJECTIVE: Diabetes may influence the outcome of complicated peptic ulcer
      disease, due to angiopathy, blurring of symptoms, and increased risk of sepsis.
      We examined whether diabetes increased 30-day mortality among Danish patients
      hospitalized with bleeding or perforated peptic ulcers. RESEARCH DESIGN AND
      METHODS: This population-based cohort study took place in the three Danish
      counties of North Jutland, Viborg, and Aarhus between 1991 and 2003. Patients
      hospitalized with a first-time diagnosis of peptic ulcer bleeding or perforation
      were identified using the counties' hospital discharge registries. Data on
      diabetes, other comorbidities, and use of ulcer-associated drugs were obtained
      from discharge registries and prescription databases. The Danish Civil Registry
      System allowed complete follow-up for mortality. The outcome under study was 30
      day mortality in diabetic versus nondiabetic patients, adjusted for potential
      confounders. RESULTS: We identified 7,232 patients hospitalized for bleeding
      ulcers, of whom 731 (10.1%) had diabetes. The 30-day mortality among diabetic
      patients was 16.6 vs. 10.1% for other patients with bleeding ulcers. The adjusted
      30-day mortality rate ratio (MRR) for diabetic patients was 1.40 (95% CI 1.15
      1.70). We also identified 2,061 patients with perforated ulcers, of whom 140
      (6.8%) had diabetes. The 30-day mortality among diabetic patients was 42.9 vs.
      24.0% in other patients with perforated ulcers, corresponding to an adjusted 30
      day MRR of 1.51 (1.15-1.98). CONCLUSIONS: Among patients with peptic ulcer
      bleeding and perforation, diabetes appears to be associated with substantially
      increased short-term mortality.

PMID- 16567820
TI  - Translating the chronic care model into the community: results from a randomized
      controlled trial of a multifaceted diabetes care intervention.
AB  - OBJECTIVE: To determine whether using the chronic care model (CCM) in an
      underserved community leads to improved clinical and behavioral outcomes for
      people with diabetes. RESEARCH DESIGN AND METHODS: This multilevel, cluster
      design, randomized controlled trial examined the effectiveness of a CCM-based
      intervention in an underserved urban community. Eleven primary care practices,
      along with their patients, were randomized to three groups: CCM intervention (n =
      30 patients), provider education only (PROV group) (n = 38), and usual care (UC
      group) (n = 51). RESULTS: A marked decline in HbA(1c) was observed in the CCM
      group (-0.6%, P = 0.008) but not in the other groups. The magnitude of the
      association remained strong after adjustment for clustering (P = 0.01). The same
      pattern was observed for a decline in non-HDL cholesterol and for the proportion
      of participants who self-monitor blood glucose in the CCM group (non-HDL
      cholesterol: -10.4 mg/dl, P = 0.24; self-monitor blood glucose: +22.2%, P <
      0.0001), with statistically significant between-group differences in improvement
      (non-HDL cholesterol: P = 0.05; self-monitor blood glucose: P = 0.03) after
      adjustment. The CCM group also showed improvement in HDL cholesterol (+5.5 mg/dl,
      P = 0.0004), diabetes knowledge test scores (+6.7%, P = 0.07), and empowerment
      scores (+2, P = 0.02). CONCLUSIONS: These results suggest that implementing the
      CCM in the community is effective in improving clinical and behavioral outcomes
      in patients with diabetes.

PMID- 16567821
TI  - Attributions of adolescents with type 1 diabetes in social situations:
      relationship with expected adherence, diabetes stress, and metabolic control.
AB  - OBJECTIVE: To examine the relationships among negative attributions of friend
      reactions (NAFRs) within a social context, anticipated adherence difficulties,
      diabetes stress, and metabolic control. RESEARCH DESIGN AND METHODS: A sample of
      104 adolescents with type 1 diabetes completed instruments measuring
      demographics, attribution of friend reactions, anticipated adherence, and
      diabetes stress. Metabolic control was measured by HbA(1c) obtained during the
      clinic visit. RESULTS: Path analysis demonstrated an excellent fit of a model
      depicting an indirect relationship between NAFRs and metabolic control through
      the mechanisms of expected adherence difficulties and diabetes stress.
      CONCLUSIONS: Adolescents who make NAFRs are likely to find adherence difficult in
      social situations and have increased feelings of stress, with the latter
      associated with poorer metabolic control. Intervention efforts to address
      negative attributions may impact adherence behavior and feelings of stress,
      especially if specific contexts of self-care behavior are taken into account.

PMID- 16567822
TI  - Is self-efficacy associated with diabetes self-management across race/ethnicity
      and health literacy?
AB  - OBJECTIVE: Although prior research demonstrated that improving diabetes self
      efficacy can improve self-management behavior, little is known about the
      applicability of this research across race/ethnicity and health literacy levels.
      We examined the relationship between diabetes self-efficacy and self-management
      behavior in an urban, diverse, low-income population with a high prevalence of
      limited health literacy. RESEARCH DESIGN AND METHODS: We administered an oral
      questionnaire in Spanish and English to patients with type 2 diabetes at two
      primary care clinics at a public hospital. We measured self-efficacy, health
      literacy, and self-management behaviors using established instruments. We
      performed multivariate regressions to explore the associations between self
      efficacy and self-management, adjusting for clinical and demographic factors. We
      tested for interactions between self-efficacy, race/ethnicity, and health
      literacy on self-management. RESULTS: The study participants were ethnically
      diverse (18% Asian/Pacific Islander, 25% African American, 42% Latino/a, and 15%
      white), and 52% had limited health literacy (short version of the Test of
      Functional Health Literacy in Adults score <23). Diabetes self-efficacy was
      associated with four of the five self-management domains (P < 0.01). After
      adjustment, with each 10% increase in self-efficacy score, patients were more
      likely to report optimal diet (0.14 day more per week), exercise (0.09 day more
      per week), self-monitoring of blood glucose (odds ratio 1.16), and foot care
      (1.22), but not medication adherence (1.10, P = 0.40). The associations between
      self-efficacy and self-management were consistent across race/ethnicity and
      health literacy levels. CONCLUSIONS: Self-efficacy was associated with self
      management behaviors in this vulnerable population, across both race/ethnicity
      and health literacy levels. However, the magnitude of the associations suggests
      that, among diverse populations, further study of the determinants of and
      barriers to self-management is warranted. Policy efforts should be focused on
      expanding the reach of self-management interventions to include ethnically
      diverse populations across the spectrum of health literacy.

PMID- 16567823
TI  - Depression and glycemic control in elderly ethnically diverse patients with
      diabetes: the IDEATel project.
AB  - OBJECTIVE: The purpose of the study was to investigate the effect of comorbid
      depression on glycemic control and on response to a telemedicine case management
      intervention for elderly, ethnically diverse diabetic patients. RESEARCH DESIGN
      AND METHODS: Medicare beneficiaries in underserved areas were participants (n =
      1,665) in the Informatics for Diabetes Education and Telemedicine (IDEATel)
      project and randomized to a telemedicine case management intervention or usual
      care. The data analyzed include baseline demographics (age, sex, race/ethnicity,
      marital status, insulin use, years of education, years of diabetes, and pack
      years smoked) and measures of glycemic control (HbA(1c) [A1C]), comorbidity,
      diabetes symptom severity, functional disability and depression, and 1-year (n =
      1,578) A1C. The association between depression and glycemic control was analyzed
      cross-sectionally and prospectively. RESULTS: At baseline, there was a
      significant correlation between depression and A1C and a trend for depression to
      predict A1C when other factors were controlled. However, in prospective analyses,
      depression did not predict change in A1C, either in the control or intervention
      group. CONCLUSIONS: In this large sample of elderly diabetic patients, a weak
      relationship between depression and A1C was found, but depression did not
      prospectively predict change in glycemic control. Thus, there is no evidence that
      depression should be used to exclude patients from interventions. Also, we should
      evaluate the impact of depression on outcomes other than glycemic control.

PMID- 16567824
TI  - Antihypertensive medication prescribing in 27,822 elderly Canadians with diabetes
      over the past decade.
AB  - OBJECTIVE: The purpose of this study was to examine whether prescribing practices
      for elderly individuals with diabetes and hypertension changed over the past
      decade. RESEARCH DESIGN AND METHODS: We linked the Ontario Diabetes Database and
      four administrative databases in Ontario, Canada, to identify 27,822 patients >65
      years of age who had diabetes and were newly treated for hypertension between 1
      January 1995 and 31 December 2001. All patients were followed for 2 years after
      their initial antihypertensive medication prescription. RESULTS: The 27,822
      patients in this study (mean age 72 years, 51% men) were treated with oral
      hypoglycemic agents alone (n = 17,128 patients, 62%), insulin alone (n = 2,346,
      8%), both oral hypoglycemic agents and insulin (n = 2,205, 8%), or diet alone (n
      = 6,143, 22%). Management within the first 2 years of hypertension diagnosis
      consisted of antihypertensive monotherapy in 20,183 patients (73%), two
      antihypertensive drugs in 6,207 (22%), and three or more drugs in 1,432 (5%); the
      most frequently chosen antihypertensive drugs were ACE inhibitors (68%),
      thiazides (15%), and calcium channel blockers (9%). Between 1995 and 2001,
      physician prescribing practices changed: the population-adjusted rates of
      antihypertensive drug prescribing increased by 46% (95% CI 33-55%), the
      proportion of initial antihypertensive prescriptions for ACE inhibitors increased
      from 54 to 76% (P < 0.0001), and the use of multiple antihypertensive agents
      within the first 2 years of diagnosis increased from 21 to 32% (P < 0.0001).
      CONCLUSIONS: Antihypertensive prescribing patterns in elderly individuals with
      diabetes changed over the past decade in Ontario in directions consistent with
      the evolving evidence base.

PMID- 16567825
TI  - Choice of antibody immunotherapy influences cytomegalovirus viremia in
      simultaneous pancreas-kidney transplant recipients.
AB  - OBJECTIVE: Simultaneous pancreas-kidney (SPK) transplantation in type 1 diabetic
      patients requires immunotherapy against allo- and autoreactive T-cells.
      Cytomegalovirus (CMV) infection is a major cause for morbidity after
      transplantation and is possibly related to recurrent autoimmunity. In this study,
      we assessed the pattern of CMV viremia in SPK transplant recipients receiving
      either antithymocyte globulin (ATG) or anti-CD25 (daclizumab) immunosuppressive
      induction therapy. RESEARCH DESIGN AND METHODS: We evaluated 36 SPK transplant
      recipients from a randomized cohort that received either ATG or daclizumab as
      induction therapy. Patients at risk for CMV infection received oral prophylactic
      ganciclovir therapy. The CMV DNA level in plasma was measured for at least 180
      days using a quantitative real-time PCR. Recipient peripheral blood mononuclear
      cells were cross-sectionally HLA tetramer-stained for CMV-specific CD8(+) T
      cells. RESULTS: Positive CMV serostatus in donors was correlated with a higher
      incidence of CMV viremia than negative serostatus. In patients at risk,
      daclizumab induction therapy significantly prolonged CMV-free survival. CMV
      viremia occurred earlier and was more severe in patients with rejection episodes
      than in patients without rejection episodes. CMV-specific CD8(+) T-cell counts
      were significantly lower in patients developing CMV viremia than in those who did
      not. CONCLUSIONS: Despite their comparable immunosuppressive potential,
      daclizumab is safer than ATG regarding CMV infection risk in SPK transplantation.
      ATG-treated rejection episodes are associated with earlier and more severe
      infection. Furthermore, high CMV-specific tetramer counts reflect antiviral
      immunity rather than concurrent viremia because they imply low viremic activity.
      These findings may prove valuable in the discussion on both safety of induction
      therapy and recurrent autoimmunity in SPK and islet transplantation.

PMID- 16567826
TI  - Tissue gene expression of renin-angiotensin system in human type 2 diabetic
      nephropathy.
AB  - OBJECTIVE: Recent studies have proved that blockade of the renin-angiotensin
      system (RAS) retards the progression of diabetic nephropathy, whereas
      hyporeninemia is known as a typical state in diabetic subjects. The purpose of
      this study is to determine whether expression levels of RAS differ between
      nondiabetic and diabetic renal tissues with accurate quantitative method.
      RESEARCH DESIGN AND METHODS: Subjects were 66 nondiabetic and 8 diabetic patients
      with biopsy-proven renal diseases. The eight diabetic subjects suffered from type
      2 diabetes with overt proteinuria. Renal histology revealed typical diffuse or
      nodular lesions with linear IgG deposit on immunofluorescent staining and
      thickened basement membrane on electronic microscopy. Total RNA from a small part
      of the renal cortical biopsy specimens was reverse-transcribed, and the resultant
      cDNA was amplified for new major components of RAS (i.e., renin, renin receptor,
      angiotensinogen, ACE, ACE2, angiotensin II type 1 receptor, and angiotensin II
      type 2 receptor) and measured. RESULTS: Among these components, a significant
      upregulation was observed in the ACE gene in diabetic renal tissue. CONCLUSIONS:
      The results suggest that renal tissue RAS might be activated in the respect that
      ACE gene expression is upregulated in spite of a tendency to low renin expression
      in type 2 diabetic nephropathy.

PMID- 16567827
TI  - Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin
      resistance and fat accumulation in the liver in humans.
AB  - OBJECTIVE: The alpha(2)-Heremans-Schmid glycoprotein (AHSG; fetuin-A in animals)
      impairs insulin signaling in vitro and in rodents. Whether AHSG is associated
      with insulin resistance in humans is under investigation. In an animal model of
      diet-induced obesity that is commonly associated with hepatic steatosis, an
      increase in Ahsg mRNA expression was observed in the liver. Therefore, we
      hypothesized that the AHSG plasma protein, which is exclusively secreted by the
      liver in humans, may not only be associated with insulin resistance but also with
      fat accumulation in the liver. RESEARCH DESIGN AND METHODS: Data from 106 healthy
      Caucasians without type 2 diabetes were included in cross-sectional analyses. A
      subgroup of 47 individuals had data from a longitudinal study. Insulin
      sensitivity was measured by a euglycemic-hyperinsulinemic clamp, and liver fat
      was determined by (1)H magnetic resonance spectroscopy. RESULTS: AHSG plasma
      levels, adjusted for age, sex, and percentage of body fat, were higher in
      subjects with impaired glucose tolerance compared with subjects with normal
      glucose tolerance (P = 0.006). AHSG plasma levels were negatively associated with
      insulin sensitivity (r = -0.22, P = 0.03) in cross-sectional analyses. Moreover,
      they were positively associated with liver fat (r = 0.27, P = 0.01). In
      longitudinal analyses, under weight loss, a decrease in liver fat was accompanied
      by a decrease in AHSG plasma concentrations. Furthermore, high AHSG levels at
      baseline predicted less increase in insulin sensitivity (P = 0.02). CONCLUSIONS:
      We found that high AHSG plasma levels are associated with insulin resistance in
      humans. Moreover, AHSG plasma levels are elevated in subjects with fat
      accumulation in the liver. This is consistent with a potential role of AHSG as a
      link between fatty liver and insulin resistance.

PMID- 16567829
TI  - Polymorphisms of the protein kinase C-beta gene (PRKCB1) accelerate kidney
      disease in type 2 diabetes without overt proteinuria.
AB  - OBJECTIVE: We investigated the contribution of PKC-beta gene (PRKCB1)
      polymorphisms to diabetic kidney disease in a prospective observational follow-up
      study. RESEARCH DESIGN AND METHODS: A total of 364 Japanese subjects with type 2
      diabetes without overt proteinuria were enrolled during 1996-1998 and followed
      until 2004. Five single nucleotide polymorphisms (-1504C/T, -546C/G, -348A/G, 
      278C/T, and -238C/G) in the promoter region of PRKCB1 were genotyped. The end
      points were transition from stage to stage of diabetic nephropathy as a time-to
      event outcome and the annual decline rate of estimated glomerular filtration rate
      (eGFR) as a slope-based outcome. RESULTS: During the study (median 6 years), 34
      of 364 subjects (9.3%) progressed. Kaplan-Meier estimation revealed that subjects
      with both T allele at -1054 C/T and G allele at -546 C/G polymorphisms frequently
      showed transition to advanced stages of diabetic nephropathy (P = 0.015). The
      annual change rate in eGFR in the subjects with both alleles was also
      significantly higher than in others (-2.96 +/- 0.62 vs. -1.63 +/- 0.15 ml/min per
      1.73 m(2)/year, P = 0.02). The estimated frequency of this risk T-G haplotype was
      significantly higher in the progressors who showed transition to advanced
      nephropathy stages (12%) than in the nonprogressors (5%) (odds ratio 2.3 [95% CI
      1.0-5.2]), and it was also higher in those with accelerated decline of the Delta
      eGFR (> or =3 ml/min per 1.73 m(2)/year) than in those without (2.1 [1.1-3.9]).
      CONCLUSIONS: Our study indicates that PRKCB1 is a predictor for worsening of
      kidney disease in Japanese subjects with type 2 diabetes.

PMID- 16567828
TI  - Risk of celiac disease in children with type 1 diabetes is modified by positivity
      for HLA-DQB1*02-DQA1*05 and TNF -308A.
AB  - OBJECTIVE: The overlap between genetic susceptibility to celiac disease (CD) and
      to type 1 diabetes is incomplete; therefore, some genetic polymorphisms may
      significantly modify the risk of CD in subjects with type 1 diabetes. This study
      aimed to investigate whether the susceptibility to CD in diabetic children is
      modified by positivity for HLA-DQB1*02-DQA1*05 and DQB1*0302-DQA1*03 and by
      alleles of single nucleotide polymorphisms within the genes encoding CTLA4,
      transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha,
      interferon (IFN)-gamma, interleukin (IL)-1, IL-2, IL-6, and IL-10. RESEARCH
      DESIGN AND METHODS: Genotypic data were compared between 130 case subjects
      (children with type 1 diabetes and CD diagnosed using endomysium antibodies) and
      245 control subjects (children with type 1 diabetes only, optimally two per case,
      matched for center, age at type 1 diabetes onset, and type 1 diabetes duration).
      The subjects were recruited from 10 major European pediatric diabetes centers
      performing regular screening for CD. The polymorphisms were determined using PCR
      with sequence-specific primers, and the risk was assessed by building a step-up
      conditional logistic regression model using variables that were significantly
      associated with CD in the univariate analysis. RESULTS: The best-fitted model
      showed that risk of CD is increased by presence of HLA-DQB1*02-DQA1*05 (odds
      ratio 4.5 [95% CI 1.8-11], for homozygosity, and 2.0 [1.1-3.7], for a single
      dose) and also independently by TNF -308A (1.9 [1.1-3.2], for phenotypic
      positivity), whereas IL1-alpha -889T showed a weak negative association (0.6 [0.4
      0.9]). CONCLUSIONS: The results indicate that the risk of CD in children with
      type 1 diabetes is significantly modified both by the presence of HLA-DQB1*02
      DQA1*05 and by a variant of another gene within the major histocompatibility
      complex, the TNF -308A.

PMID- 16567830
TI  - Pioglitazone treatment improves nitrosative stress in type 2 diabetes.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of 24 weeks of
      treatment with 45 mg/day pioglitazone on peripheral skin blood flow (SkBF) and
      skin nitric oxide (NO) production in vivo in patients with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: This was a randomized, parallel, cross-over, double
      blind, within- and between-subject study designed to compare vascular responses
      before and after treatment. We studied 12 subjects with type 2 diabetes (average
      age 58.6 +/- 30.8 years, HbA(1c) 7.9 +/- 00.4%, BMI 31.3 +/- 1.2 kg/m(2)). SkBF
      was measured using laser Doppler techniques in response to ischemia reperfusion
      and local skin warming, and NO production was assessed in vivo using an
      amperometric NO meter inserted directly into the skin. These measurements were
      performed before treatment and at 6 and 24 weeks. RESULTS: The SkBF response was
      not significantly improved after 24 weeks in either of the groups. NO production
      was significantly decreased in the pioglitazone-treated group in the basal
      condition (area under the curve 6.4 +/- 1.0 vs. 2.8 +/- 0.8, P < 0.01), after
      local heat stimulation at 40 degrees C (12.9 +/- 2.2 vs. 5.7 +/- 1.7, P < 0.01),
      and after nociceptor stimulated flow with local heating at 44 degrees C (36.4 +/-
      6.3 vs. 16.6 +/- 3.4). Differences were not significant in the placebo-treated
      group. CONCLUSIONS: Treatment of patients with type 2 diabetes with pioglitazone
      for 24 weeks reduced skin NO production, thus probably reducing nitrosative
      stress without a demonstrable effect on SkBF. Because nitrosative stress is
      considered to be a factor in the pathogenesis of neurovascular dysfunction, these
      findings warrant further investigation.

PMID- 16567831
TI  - HbA1c and peripheral arterial disease in diabetes: the Atherosclerosis Risk in
      Communities study.
AB  - OBJECTIVE: To assess the relation between HbA(1c) (A1C) and incident peripheral
      arterial disease (PAD) in a community-based cohort of diabetic adults from the
      Atherosclerosis Risk in Communities (ARIC) study. A second aim was to investigate
      whether the association was stronger for severe, symptomatic disease compared
      with PAD assessed by low ankle-brachial index (ABI). RESEARCH DESIGN AND METHODS:
      This was a prospective cohort study of 1,894 individuals with diabetes using ARIC
      visit 2 as baseline (1990-1992) with follow-up for incident PAD through 2002. We
      assessed the relation between A1C and incident PAD, defined by intermittent
      claudication, PAD-related hospitalization, or a low ABI (<0.9). RESULTS: During a
      mean follow-up of 9.8 years, the crude incidence rates were 2.1 per 1,000 person
      years for intermittent claudication (n = 41), 2.9 per 1,000 person-years for PAD
      related hospitalization (n = 57), and 18.9 per 1,000 person-years for low ABI at
      visit 3 or 4 (n = 123). The relative risk (RR) (95% CI) of an incident PAD event
      comparing the second and third tertiles of A1C to the first, respectively, after
      adjustment for cardiovascular risk factors was strongest for severe, symptomatic
      forms of disease, e.g., PAD-related hospitalization (RR = 4.56 [1.86-11.18] for
      the third A1C tertile compared with the first, P trend <0.001) than for low ABI
      (RR = 1.64 [0.94-2.87], P trend = 0.08). CONCLUSIONS: We found a positive,
      graded, and independent association between A1C and PAD risk in diabetic adults.
      This association was stronger for clinical (symptomatic) PAD, whose
      manifestations may be related to microvascular insufficiency, than for low ABI.
      Our results suggest that efforts to improve glycemic control in persons with
      diabetes may substantially reduce the risk of PAD.

PMID- 16567832
TI  - The relationship among pain, sensory loss, and small nerve fibers in diabetes.
AB  - OBJECTIVE: Many individuals with diabetes experience neuropathic pain, often
      without objective signs of large-fiber neuropathy. We examined intraepidermal
      nerve fibers (IENFs) to evaluate the role of small nerve fibers in the genesis of
      neuropathic pain. RESEARCH DESIGN AND METHODS: Twenty-five diabetic subjects with
      neuropathic pain and 13 without were studied. The pain was present for at least 6
      months for which no other cause could be found. Punch skin biopsies were obtained
      from the distal leg. IENFs were stained using antibody to protein gene product
      9.5 and counted with confocal microscopy. Neuropathy was graded by vibration
      perception and cold detection thresholds and the Michigan Neuropathy Screening
      Instrument. RESULTS: In the total cohort, IENF density was significantly lower in
      those with pain compared with those without (3 [1-6] vs. 10 [3-19], respectively,
      P = 0.02). There were significant inverse correlations between IENF and severity
      of neuropathy, with the pain group having a flatter gradient than their pain-free
      counterparts (P < 0.02). The difference in IENF density was greatest in subjects
      with less objective evidence of neuropathy (P < or = 0.01). CONCLUSIONS: More
      severe loss of IENF is associated with the presence of neuropathic pain only in
      those with little or no objective sign of neuropathy. Thus, loss of IENF cannot
      explain pain in all cases, suggesting that different mechanisms underpin the
      genesis of pain at various stages of neuropathy.

PMID- 16567833
TI  - Uncoupling protein 2 promoter polymorphism -866G/A affects peripheral nerve
      dysfunction in Japanese type 2 diabetic patients.
AB  - OBJECTIVE: To determine genetic predispositions for diabetic polyneuropathy, we
      investigated the relationship between the -866G/A polymorphism of uncoupling
      protein (UCP) 2 and neurological manifestations in 197 type 2 diabetic patients.
      RESEARCH DESIGN AND METHODS: We first examined whether UCP2 mRNA had been
      expressed in the dorsal root ganglion (DRG) in four Long-Evans Tokushima Otsuka
      rats using RT-PCR and electrophoresis. Genotyping of UCP2 promoter polymorphism 
      866G/A was then performed in 197 unrelated Japanese type 2 diabetic patients, who
      were subjected to nerve conduction, quantitative vibratory perception, head-up
      tilt, and heart rate variability tests, by PCR restriction fragment-length
      polymorphism. The relationships between UCP2 genotype and various nerve functions
      were analyzed by uni- and multivariable analysis. RESULTS: Expression of UCP2
      mRNA was confirmed in rat DRG. Multiple regression analysis clarified the
      hypothesis that the G/A + A/A genotype was significantly related to decreased
      motor nerve conduction velocity and impaired blood pressure maintenance on the
      head-up tilt test. Multiple logistic regression analysis revealed that the G/A +
      A/A genotypes are a significant risk factor for sensory nerve conduction slowing
      and orthostatic hypotension. CONCLUSIONS: UCP2 promoter gene polymorphism -866
      G/A was significantly associated with nerve conduction slowing and vasomotor
      sympathetic functions. These findings suggest that the higher UCP2 activity
      related to the A allele has an energy-depleting effect on peripheral nerve
      function in type 2 diabetic patients.

PMID- 16567834
TI  - Altered fiber distribution and fiber-specific glycolytic and oxidative enzyme
      activity in skeletal muscle of patients with type 2 diabetes.
AB  - OBJECTIVE: We investigated whether alterations of glycolytic and oxidative enzyme
      capacity in skeletal muscle of patients with type 2 diabetes pertain to specific
      muscle fibers and are associated with changes in muscle fiber composition.
      RESEARCH DESIGN AND METHODS: Vastus lateralis muscle was obtained by percutaneous
      biopsy from 10 patients with type 2 diabetes and 15 age- and BMI-matched healthy
      volunteers. Using cytophotometry, muscle fiber composition and fiber type
      specific glycolytic and oxidative enzyme activities were measured in slow
      oxidative, fast oxidative glycolytic, and fast glycolytic fibers. RESULTS: In the
      whole muscle, oxidative activity was decreased in patients with type 2 diabetes.
      The slow oxidative fiber fraction was reduced by 16%, whereas the fast glycolytic
      fiber fraction was increased by 49% in skeletal muscle from the diabetic
      patients. Both oxidative and glycolytic enzyme activities were significantly
      increased in fast glycolytic and fast oxidative glycolytic fibers of type 2
      diabetic patients. However, the fiber-specific ratio of glycolytic enzyme
      activity relative to oxidative activity was not different between type 2 diabetic
      patients and the control subjects. The myofibrillic ATP activity was
      significantly lower in all fiber types of patients with type 2 diabetes and
      correlates with glucose infusion rate during the steady state of a euglycemic
      hyperinsulinemic clamp and maximal aerobic capacity and negatively with HbA(1c)
      values. CONCLUSIONS: Reduced oxidative enzyme activity in muscle of type 2
      diabetic patients is most likely due to a reduction in slow oxidative fibers.
      Increased glycolytic and oxidative enzyme activities in individual muscle fibers
      are closely related to measures of long-term glycemic control and whole-body
      insulin sensitivity and could therefore represent a compensatory mechanism of the
      muscle in function of the altered glucose metabolism.

PMID- 16567835
TI  - Adult Treatment Panel III 2001 but not International Diabetes Federation 2005
      criteria of the metabolic syndrome predict clinical cardiovascular events in
      subjects who underwent coronary angiography.
AB  - OBJECTIVE: The International Diabetes Federation (IDF) has recently established a
      worldwide consensus definition of the metabolic syndrome. No prospective data are
      available on the cardiovascular risk associated with this new metabolic syndrome
      definition. RESEARCH DESIGN AND METHODS: In a prospective study of 750 coronary
      patients, we recorded vascular events over 4 years. RESULTS: From our patients,
      37.3% (n = 280) had the metabolic syndrome according to the Adult Treatment Panel
      III (ATPIII) definition and 45.5% (n = 341) according to the IDF definition. The
      metabolic syndrome as defined by the ATPIII criteria significantly predicted
      vascular events (adjusted hazard ratio 1.745 [95% CI 1.255-2.427]; P = 0.001),
      but the metabolic syndrome as defined by IDF criteria did not (1.189 [0.859
      1.646]; P = 0.297). Accordingly, event-free survival was significantly lower
      among patients who fulfilled the ATPIII but not the IDF criteria than among those
      who met the IDF but not the ATPIII criteria (P = 0.012). The metabolic syndrome
      as defined by ATPIII criteria remained significantly predictive of vascular
      events after adjustment for type 2 diabetes but not after additional adjustment
      for the metabolic syndrome components high triglycerides and low HDL cholesterol.
      These lipid traits in turn proved significantly predictive of vascular events
      even after adjustment for the metabolic syndrome. CONCLUSIONS: The ATPIII
      definition of the metabolic syndrome confers a significantly higher risk of
      vascular events than the IDF definition. However, among angiographied coronary
      patients, even the ATPIII definition of the metabolic syndrome does not provide
      prognostic information beyond its dyslipidemic features.

PMID- 16567836
TI  - Alcohol consumption in relation to metabolic regulation, inflammation, and
      adiponectin in 64-year-old Caucasian women: a population-based study with a focus
      on impaired glucose regulation.
AB  - OBJECTIVE: The aims of this study were to examine alcohol drinking patterns in
      women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose
      tolerance (NGT) and to investigate whether alcohol intake was associated with
      improved insulin sensitivity, decreased biomarkers of inflammation, and increased
      adiponectin levels and if these effects were limited to dysmetabolic women.
      RESEARCH DESIGN AND METHODS: From a cohort of 64-year-old Caucasian women, 209
      with type 2 diabetes, 205 with IGT, and 186 with NGT were recruited. Alcohol
      consumption and medication use were assessed by questionnaires. Anthropometric
      data were collected, and blood glucose, insulin, HDL cholesterol, triglycerides,
      C-reactive protein, white blood cell count, and serum adiponectin were measured.
      RESULTS: Compared with the NGT group, alcohol consumption was lower in the IGT
      group and lowest in the diabetes group. Mean alcohol intakes of >9.2 and > or =3
      9 g/day were positively associated with adiponectin and insulin sensitivity
      (homeostasis model assessment [HOMA]), respectively, independently of obesity,
      metabolic control, and other confounders. Alcohol intake correlated negatively
      with inflammatory markers, although this did not remain after adjustment for HOMA
      and waist circumference. The inverse associations between alcohol consumption and
      factors related to the metabolic syndrome such as HOMA, waist circumference, and
      inflammatory markers were more obvious among women with diabetes and IGT than in
      healthy women. CONCLUSIONS: In these women, moderate alcohol consumption showed
      beneficial associations with the prevalence of type 2 diabetes, IGT, insulin
      sensitivity, and serum adiponectin. There is a need to clarify whether
      adiponectin may be a mechanistic link and also to clarify the clinical
      implications of these observations.

PMID- 16567838
TI  - Impact of routine stenting on clinical outcome in diabetic patients undergoing
      primary angioplasty for ST-segment elevation myocardial infarction.

PMID- 16567837
TI  - The association among autonomic nervous system function, incident diabetes, and
      intervention arm in the Diabetes Prevention Program.
AB  - OBJECTIVE: Autonomic nervous system dysfunction, a correlate of obesity and poor
      cardiorespiratory fitness, is associated with the development of diabetes. We
      tested whether estimates of autonomic nervous system function improved in the
      intensive lifestyle versus metformin or placebo arms of the Diabetes Prevention
      Program (DPP) and whether baseline or a change in autonomic nervous system
      function was associated with the development of diabetes over 3.2 years. RESEARCH
      DESIGN AND METHODS: In 2,980 DPP participants, 12-lead electrocardiograms were
      measured at baseline and annually. Heart rate, heart rate variability (HRV), and
      QT duration were used to estimate fitness and autonomic nervous system function.
      RESULTS: In the lifestyle arm, heart rate and QT indexes decreased, and HRV
      increased over time. The magnitude of decline in heart rate and QT duration was
      substantially smaller in the other arms, whereas HRV did not increase. Baseline
      heart rate was the only index significantly (P < 0.05) associated with incident
      diabetes after adjustment for demographics and weight change (hazard ratio for
      lifestyle and metformin arms = 1.19 and 1.17 per 10.6 beats/min, respectively).
      Decreases in heart rate and QT indexes and increases in HRV over time were
      associated with a lower risk of developing diabetes. The protective association
      between decreased heart rate and incident diabetes in the lifestyle arm remained
      significant after accounting for change in weight and physical activity.
      CONCLUSIONS: Indexes that reflect autonomic function and fitness improved (i.e.,
      heart rate decreased and HRV increased) in the lifestyle modification arm of the
      DPP. Improvements in these indexes are inversely associated with the development
      of diabetes independent of weight change.

PMID- 16567839
TI  - Albumin-to-creatinine ratio in random urine samples might replace 24-h urine
      collections in screening for micro- and macroalbuminuria in pregnant woman with
      type 1 diabetes.

PMID- 16567840
TI  - Human insulin-induced lipoatrophy: a successful treatment with glucocorticoid.

PMID- 16567841
TI  - Synergistic association of metabolic syndrome and overt nephropathy with elevated
      asymmetric dimethylarginine in serum and impaired cutaneous microvasodilation in
      patients with type 2 diabetes.

PMID- 16567842
TI  - C-reactive protein and metabolic syndrome in elderly women: a 12-year follow-up
      study.

PMID- 16567843
TI  - Prevalence of the metabolic syndrome among Korean adults according to the
      criteria of the International Diabetes Federation.

PMID- 16567844
TI  - Pancreas and islet transplantation in type 1 diabetes.

PMID- 16567845
TI  - Insulin treatment and type 1 diabetes topics.

PMID- 16567846
TI  - An exploratory study into the effectiveness of a combination of traditional
      Chinese herbs in the management of type 2 diabetes.

PMID- 16567847
TI  - Probing the validity of the probe-to-bone test in the diagnosis of osteomyelitis
      of the foot in diabetes.

PMID- 16567848
TI  - A case of fulminant type 1 diabetes associated with painless thyroiditis.

PMID- 16567849
TI  - Severe injection site reaction to insulin detemir.

PMID- 16567850
TI  - Recurrence of diabetes after diarrhea-associated hemolytic uremic syndrome.

PMID- 16567851
TI  - Maternal age and prevalence of gestational diabetes mellitus.

PMID- 16567852
TI  - Soluble tumor necrosis factor receptor 1 is strongly and independently associated
      with serum homocysteine in nonobese Japanese type 2 diabetic patients.

PMID- 16567853
TI  - Maternal weight gain is associated with infant insulin concentrations during the
      1st year of life.

PMID- 16567854
TI  - Phenformin-induced lactic acidosis in an older diabetic patient: a recurrent
      drama (phenformin and lactic acidosis).

PMID- 16567855
TI  - Patient self-management of insulin doses in the hospital.

PMID- 16567857
TI  - Risk factors associated with healing chronic diabetic foot ulcers: the importance
      of hyperglycemia.
AB  - Diabetic foot ulcer management presents a significant challenge for wound care
      clinicians; numerous approaches to encourage healing in these difficult wounds
      have been explored. To determine risk factors related to diabetic foot ulcer time
      to healing and closure, a secondary analysis of data from a prospective
      randomized study involving 245 patients treated with a bioengineered human dermal
      substitute (n = 130) or control treatment (n = 115) was conducted. Analyzed
      variables included age, race, gender, ulcer duration, initial ulcer size, initial
      hemoglobin (HgbA1c), average HgbA1c, change in HgbA1c, diabetes type, average
      hours of weight-bearing, study ulcer infection, history of smoking or alcohol
      use, and laboratory values. Time to healing was significantly affected by initial
      ulcer size (risk ratio 0.75, confidence interval 0.59-0.96), gender (risk ratio
      2.01, confidence interval 1.20-3.40), and wound infection during the study (risk
      ratio 2.9, confidence interval 1.45-4.22). Initial ulcer size (>2 cm2), male
      gender, and an episode of infection during the study were associated with an
      increased risk of nonclosure after 12 weeks of care (P <0.05). In patients whose
      HgbA1C increased during the study (n = 101), 20.7% of all wounds and 21% of
      dermal substitute-managed wounds (n = 105) healed; whereas, in patients whose
      HgbA1C levels remained stable or decreased, 26.3% of all wounds and 47% of dermal
      substitute-managed wounds healed (P <0.05). Female gender, small ulcer size, and
      the absence of infection were found to have a positive effect on healing all
      diabetic foot ulcers; improved glucose control had a significant effect on
      healing wounds managed with the dermal substitute only. This is the first
      diabetic foot ulcer study to find a relationship between hyperglycemia and wound
      healing. Further research into factors that improve healing of wounds, including
      diabetic foot ulcers, is warranted.

PMID- 16567856
TI  - Assessing the effects of LXR agonists on cellular cholesterol handling: a stable
      isotope tracer study.
AB  - The liver X receptors (LXRs) alpha and beta are responsible for the
      transcriptional regulation of a number of genes involved in cholesterol efflux
      from cells and therefore may be molecular targets for the treatment of
      cardiovascular disease. However, the effects of LXR ligands on cholesterol
      turnover in cells has not been examined comprehensively. In this study, cellular
      cholesterol handling (e.g., synthesis, catabolism, influx, and efflux) was
      examined using a stable isotope labeling study and a two-compartment modeling
      scheme. In HepG2 cells, the incorporation of 13C into cholesterol from [1
      13C]acetate was analyzed by mass isotopomer distribution analysis in conjunction
      with nonsteady state, multicompartment kinetic analysis to calculate the
      cholesterol fluxes. Incubation with synthetic, nonsteroidal LXR agonists (GW3965,
      T0901317, and SB742881) increased cholesterol synthesis (approximately 10-fold),
      decreased cellular cholesterol influx (71-82%), and increased cellular
      cholesterol efflux (1.7- to 1.9-fold) by 96 h. As a consequence of these altered
      cholesterol fluxes, cellular cholesterol decreased (36-39%) by 96 h. The
      increased cellular cholesterol turnover was associated with increased expression
      of the LXR-activated genes ABCA1, ABCG1, FAS, and sterol-regulatory element
      binding protein 1c. In summary, the mathematical model presented allows time
      dependent calculations of cellular cholesterol fluxes. These data demonstrate
      that all of the cellular cholesterol fluxes were altered by LXR activation and
      that the increase in cholesterol synthesis did not compensate for the increased
      cellular cholesterol efflux, resulting in a net cellular cholesterol loss.

PMID- 16567858
TI  - Road traffic injuries & fatalities in India--a modern epidemic.

PMID- 16567860
TI  - The Journal on the move.

PMID- 16567859
TI  - Clinical safety issues in developing & testing of vaginal microbicides.

PMID- 16567861
TI  - Tumour necrosis factor & dengue.

PMID- 16567862
TI  - Cholera: time for action.

PMID- 16567863
TI  - Epigenetic therapy--a new development in pharmacology.
AB  - Epigenetics, heritable changes in gene expression that do not involve changes in
      DNA sequence, is known to be involved in disease. Two important epigenetic
      changes that are known to contribute to disease are abnormal methylation patterns
      of DNA and modifications of histones in chromatin. This review describes a new
      development in pharmacology, epigenetic therapy, which attempts to correct these
      changes. At present two groups of drugs are being developed. One inhibits DNA
      methyltransferases (DNMTs) resulting in the inhibition of DNA methylation. This
      group of drugs may prove to be useful in the treatment of cancer where
      hypermethylation of tumour suppressor genes is known to lead to silencing of
      these genes. The other group of drugs inhibits histone deacetylases (HDACs)
      resulting in the accumulation of acetylated histones which are thought to mediate
      the anticancer effects of these drugs. Both these drug groups have shown
      promising results in drug trials for the treatment of cancer. Since epigenetic
      changes are thought to underlie a wide range of diseases, the scope of epigenetic
      therapy is likely to expand.

PMID- 16567864
TI  - Circulating levels of tumour necrosis factor-alpha & interferon-gamma in patients
      with dengue & dengue haemorrhagic fever during an outbreak.
AB  - BACKGROUND & OBJECTIVE: Dengue haemorrhagic fever (DHF) is a severe illness
      caused by dengue viruses, the pathogenesis of which is not fully understood.
      Immune enhancement caused by cytokines, interferon and activated complement
      system is one of the hypotheses proposed to explain the haemorrhagic form of
      disease. This study was undertaken to investigate the role of pro-inflammatory
      cytokines tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN
      gamma) in dengue infection, and their possible association with disease severity.
      METHODS: Blood samples were collected from 60 patients; 28 patients of DF and 32
      of DHF (clinically categorized into DF or DHF as per WHO criteria) from September
      to November 2003 at Delhi. Fifteen healthy individuals were included as control.
      All the patients were confirmed positive for dengue infection by serology or by
      reverse transcriptase-polymerase chain reaction (RT-PCR). Serum levels of TNF
      alpha and IFN-gamma were determined by ELISA. RESULTS: The levels of both the
      cytokines were significantly elevated in the disease group as compared to the
      control group. Significantly higher levels of TNF-alpha; 258.02 pg/ml (P<0.005)
      were seen in patients having secondary infection, while patients with primary
      infection had higher level of IFN-gamma; 29.47 pg/ml (P<0.005). TNF-alpha was
      elevated in the later phase of illness, while IFN-gamma was elevated in early
      phase also. INTERPRETATION & CONCLUSION: Overproduction of TNF-alpha during
      secondary infection may have a role in immunopathogenesis of DHF, however, study
      of other cytokines produced along with IFN-gamma;, during the course of dengue
      infection is required to know the specific role of IFN-gamma in DI.

PMID- 16567865
TI  - Epidemiological, microbiological & electron microscopic study of a cholera
      outbreak in a Kolkata slum community.
AB  - BACKGROUND & OBJECTIVE: Epidemics of cholera caused by Vibrio cholerae O1 or O139
      have been reported from different parts of India. Factors such as unsafe water
      supply, poor environmental sanitation, indiscriminate defaecation and lack of
      personal hygiene are mainly responsible for continued transmission of this
      disease. We report here epidemiological and microbiological findings of a
      localized outbreak of cholera, which occurred during March and April 2004 in the
      eastern part of Kolkata city. METHODS: The affected slum area has a population of
      4409, predominantly muslims. Patients suffering from acute watery diarrhoea
      attended the health outposts organized by National Institute of Cholera and
      Enteric Diseases, Kolkata and International Vaccine Institute, South Korea as
      part of a routine surveillance programme at the locality as well as the emergency
      medical camp organized by the Kolkata Municipal Corporation. Stool and water
      samples were collected and tested for diarrhoeagenic pathogens in the laboratory.
      Bacteriophages specific for V. cholerae were isolates and studied electron
      microscopically for morphology. RESULTS: A total of 89 diarrhoea cases were
      reported giving an attack rate of 2 per cent. V. cholerae O1 biotype ElTor,
      serotype Ogawa was isolated as a sole pathogen from 15 (15.8%) of 89 stool
      samples screened. Water samples (2 from tube wells, 3 from municipal taps and 1
      from well) showed presence of coliform bacilli with high MPN (Most Probable
      Number) count. Bacteriophages specific to V. cholerae were isolated from 2 of 6
      water samples examined. A leakage was detected in the main pipeline supplying
      drinking water to that area. INTERPRETATION & CONCLUSION: The outbreak was caused
      by V. cholerae O1 (Ogawa) biotype ElTor. The presence of phages in the water
      samples was an additional indicator for V. cholerae contamination in this
      community. Occurrences of such outbreaks support vaccination against cholera as
      an alternative strategy.

PMID- 16567866
TI  - Anti-HBc & HBV-DNA detection in blood donors negative for hepatitis B virus
      surface antigen in reducing risk of transfusion associated HBV infection.
AB  - BACKGROUND & OBJECTIVE: Though sensitive screening assays for detection of
      hepatitis B virus surface antigen (HBsAg) are available, occasional cases of post
      transfusion hepatitis B virus infection (PTH) still occur. The present study was
      undertaken to assess the prevalence of anti-hepatitis B core (anti-HBc)
      positivity and presence of HBV-DNA in serum sample of healthy blood donors
      negative for both HBsAg and anti-HCV antibody in Shiraz, Iran. Since anti-HBc
      detection is not mandatory in Iran, we evaluated whether anti-HBc detection could
      be adopted as a screening assay for safety of donated blood. METHODS: Two
      thousands serum samples negative for both HBsAg and anti-HCV collected from
      healthy blood donors were tested for the presence of anti HBc antibody. All
      samples positive for anti-HBc antibody were then investigated for determination
      of anti-HBc titre, anti-HBs titre, HbeAg and anti-HBe antibody by enzyme
      immunoassay (EIA). Every sample that tested negative for HBsAg but positive for
      anti-HBc alone or in combination with other serological markers was also examined
      for the presence of HBV-DNA by polymerase chain reaction (PCR). RESULTS: Of the
      2000 samples tested, 131 (6.55%) blood samples were found to be positive for anti
      HBc. HBV DNA was detected among 16 of 131(12.2%) anti-HBc positive specimens.
      Further, there was an association between the titration of anti-HBc antibody and
      the intensity of expected PCR product band. The liver function test results were
      all in normal range except in 4 of 16 HBV-DNA positive subjects. The mean levels
      of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in HBV-PCR
      positive subjects were 14 IU/l and 23.7 IU/l respectively. INTERPRETATION &
      CONCLUSION: Anti-HBc antibody should be tested routinely on blood donors
      volunteers and if the sample found positive regardless of anti-HBs titre, the
      blood should be discarded. Further testing for HBV-DNA would be appropriate to
      follow up the donor for HBV infection.

PMID- 16567867
TI  - Increased endocytic activity in monocyte-derived dendritic cells in patients with
      psoriasis vulgaris.
AB  - BACKGROUND & OBJECTIVE: The understanding of the pathogenesis of psoriasis
      vulgaris has focused on T cell mediated immune disorder for many years. Recent
      studies provide evidence that dendritic cells may be of major importance as
      regulatory cells driving the psoriasis tissue reaction, and they are one of the
      therapeutic targets. In order to further characterize the role of dendritic cells
      in psoriasis, this study was designed to assess the differentiation of dendritic
      cells from monocytes (MoDC), the expression of phagocytosis related receptors by
      MoDC, their endocytic activity for fluorescent beads and lucifer yellow as well
      as their superoxide generation in patients with psoriasis. METHODS: Twenty eight
      patients with psoriasis vulgaris and 12 healthy controls were included in the
      study. MoDC were obtained by culturing monocytes with granulocyte macrophage
      colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 5 days. Cell
      surface expression of CD1a, CD14, CD40, CD80, CD83, CD86, HLA-DR, mannose
      receptor (MR) and Fcg receptors by MoDC and their endocytosis of dextran and
      lucifer yellow were analyzed by flow cytometry. Zymosan ingestion was measured to
      access the phagocytosis of MoDC. RESULTS: Differentiation of monocytes to
      dendritic cells was upregulated in patients manifested as significantly increased
      expression of CD40, CD80, CD86 and HLA-DR compared with that in healthy controls
      (P<0.01). Expression of MR and Fcg receptor II (CD32) by MoDC was significantly
      increased in patients with psoriasis as well (P<0.01). Endocytosis of dextran but
      not lucifer yellow in patients was significantly higher than controls (P<0.01),
      and significantly enhanced phagocytosis by increasing zymosan ingestion was also
      observed (P<0.01) in patients. Taken together, endocytic and phagocytic activity
      of MoDC in psoriasis was increased than normal persons. INTERPRETATION &
      CONCLUSION: Enhanced activity of dendritic cells binding and capturing foreign
      antigens for subsequent antigen presentation and the initiation of immune
      responses in psoriasis may contribute to the pathogenesis of the disease. The
      upregulated expression of MR and the enhanced endocytic activity of DC might be
      an explanation for the absence of skin infection observed in psoriasis.

PMID- 16567868
TI  - Serosurvey of rubella in five blocks of Tamil Nadu.
AB  - BACKGROUND & OBJECTIVE: Rubella, normally a mild, self-limiting disease
      characterized by rash, fever and lymphadenopathy, is a vaccine preventable
      disease. It carries little morbidity and apparently only minor complications in
      children. Infection during early pregnancy may lead to congenital rubella
      infection. Presence of rubella specific IgG in an unvaccinated population is a
      long term marker of previous rubella infection, which helps to assess the immune
      status of that population. Though many seroprevalence studies on rebella have
      been reported earlier from India, no study has been conducted in recent years. We
      undertook this study in 2003 in five blocks identified by the Integrated Child
      Development Scheme (ICDS), in the five districts of Tamil Nadu to assess the
      immune status to rubella in two age groups (1-5 yr boys and girls and 10-16 yr
      adolescent girls) before vaccination and draw strategies for future vaccination
      programme. METHODS: A total of 300 blood samples were collected by vein puncture
      from girls and boys of 1-5 yr age and adolescent girls of 10-16 yr age. Samples
      were tested for the presence of rubella specific IgG antibody by ELISA. RESULTS:
      Of the 300 samples tested, 145 (48.3%) were negative for rubella IgG antibodies.
      The seronegativity was 82.2 per cent in 1-5 yr and 13.5 per cent in the 10-16 yr
      age groups, the difference was statistically significant (P<0.001).
      INTERPRETATION & CONCLUSION: Large percentage of children, 82.2 per cent in the 1
      5 yr age group and 13.5 per cent in 10-16 yr population were susceptible to
      rubella infection highlighting the fact that there was a risk of congenital
      rubella syndrome. There is a need to implement routine measles, mumps, rubella
      (MMR) immunization programme for under five children and mass scale one time
      immunization with monovalent rubella vaccine for adolescent girls.

PMID- 16567869
TI  - Ultra low volume aerosol application of deltacide (deltamethrin 0.5% w/v, S
      bioallethrin 0.71% w/v & piperonyl butoxide 8.9% w/v) against mosquitoes.
AB  - BACKGROUND & OBJECTIVE: Insecticide in the form of space spray as an ultra low
      volume (ULV) aerosol are used during epidemics of vector borne diseases.
      Deltacide, a formulation comprising of three chemicals viz., deltamethrin 0.5 per
      cent w/v, S-bio-allethrin 0.71 per cent w/v and piperonyl butoxide 8.9 per cent
      w/v is suitable for ULV application. As this combination is found to be effective
      in preventing resistance development tackling the population, which had already
      developed resistance and cause immediate mortality, its synergistic effect was
      tested in Peet Grady chamber, against three species of mosquitoes, viz., Aedes
      aegypti, Anopheles stephensi and Culex quinquefasciatus. METHODS: Blood fed
      females were exposed to ULV application of deltacide in a Peet Grady chamber at
      four dosages viz., 0.005, 0.01, 0.02 and 0.04 ml/m2 and examined for knockdown
      activity at 10 min interval for 60 min. Thereafter, the mosquitoes were removed
      from the chamber and maintained in another room having controlled temperature
      (28+/-2 degrees C) and humidity (60-75%) and observed for recovery, if any, and
      the per cent knockdown was calculated. Mortality rate after 24 h of holding
      period was also determined from moribund and dead adults. RESULTS: Pairwise
      comparison showed that the effect of deltacide spray varied significantly
      (P<0.001) among the three species tested. The effectiveness was significantly
      higher in Ae. aegypti, when compared with that of Cx. quiquefasciatus (P<0.001)
      and An. stephensi (P<0.05). However, there was no significant difference in the
      efficacy of deltacide between Cx. quiquefasciatus and An. stephensi. All species
      of mosquitoes became inactive i.e., knocked down completely within 60 min of
      exposure at all the dosages tested and mortality observed was 100 per cent after
      24 h of exposure. INTERPRETATION & CONCLUSION: Deltacide when tested in the form
      of ULV cold aerosol, the dosage 0.01 ml/m2 was effective against both Ae.
      aegypti, and An. stephensi, and 0.02 ml/m2 against Cx. quiquefasciatus, causing
      100 per cent mortality. The efficacy of ULV application of deltacide against
      vector mosquitoes needs to be assessed under field conditions.

PMID- 16567870
TI  - Occurrence of Aeromonas hydrophila in acute gasteroenteritis among children.
AB  - BACKGROUND & OBJECTIVE: The interest on the occurrence multidrug resistance and
      pathogenicity of Aeromonas hydrophila is increasing worldwide since it causes
      gasteroenteritis to children. Though reports on the occurrence of
      gasteroenteritis among children due to A. hydrophila in Tamil Nadu are available
      from certain areas, no information is available from Coimbatore. Hence, this
      study was undertaken to find out the occurrence of the pathogenic A. hydrophila
      in diarrhoeal stool of children, particularly in Coimbatore region. METHODS:
      Isolation and identification of A. hydrophila was carried out from stool samples
      collected from children with acute diarrhoea. Multiple antibiotic resistance was
      determined by disc diffusion method. The pathogenicity of A. hydrophila was
      confirmed by production of haemolysin, protease and slime. RESULTS: Of the 216
      samples, 21 (9.7%) were positive for A. hydrophila. Among them 20 isolates were
      resistant to bacitracin. Most of the isolates showed multiple antibiotic
      resistance. Among the 21 isolates, protease and haemolysin producers were 100 and
      95 per cent respectively. About 76 per cent of the isolates produced slime.
      INTERPRETATION & CONCLUSION: The results of the present study indicated the
      presence of pathogenic A. hydrophila in the study area causing diarrhoea among
      children.

PMID- 16567871
TI  - Phenotypic characters of urinary isolates of Pseudomonas aeruginosa & their
      association with mouse renal colonization.
AB  - BACKGROUND & OBJECTIVE: Very few studies regarding production of virulence
      factors in different predominant serotypes of uropathogenic Pseudomonas
      aeruginosa are available and they have not been correlated to in vivo
      pathogenicity in the urinary tract. This study was carriedout with the objective
      to analyze the phenotypic characters of uroisolates of P. aeruginosa in vitro and
      to study the association of these virulence traits with their ability to cause
      nephropathogenicity in mouse model of ascending urinary tract infection (UTI).
      METHODS: Protease, elastase, alginate, haemolysin, pyochelin, pyoverdin and
      phopholipase C were measured using standard protocols in 18 uroisolates of P.
      aeruginosa isolated from patients suffering from complicated UTIs. An ascending
      model of pyelonephritis was established in Swiss Webster (LACA) female mice with
      these isolates. Quantitative bacterial count and histopathological evaluation of
      mouse renal tissue was done which were then assessed for a possible association
      with elaboration of virulence factors. RESULTS: All isolates of P. aeruginosa
      were able to colonize renal tissue of mice. However, renal counts varied amongst
      different isolates producing different virulence factors. Isolates producing high
      levels of haemolysin along with other virulence factors were able to colonize and
      multiply more in mouse renal tissue as compared to those producing low levels of
      haemolysin. INTERPRETATION & CONCLUSION: The findings of this study indicated an
      association between haemolysin production and renal colonization. High level of
      haemolysin production in vitro could be used as surrogate information for
      assessing pyelonephritic potential of P. aeruginosa.

PMID- 16567872
TI  - Androgen & vitamin D nuclear receptor expression in archival breast tumour
      samples.
AB  - BACKGROUND & OBJECTIVE: Breast tumour cells have receptors for androgen and
      vitamin D and their clinical significance is not completely understood.
      Therefore, the present study was undertaken to analyze androgen and vitamin D
      receptor levels in human primary infiltrating ductal breast carcinomas (IDC) and
      benign breast tumour archival samples and to find out their correlation, if any,
      with the clinical findings. METHODS: Paraffin blocks of benign and malignant
      breast tumours were sectioned, deparaffinized, and nuclei released by pepsin
      digestion. After antigen retrieval, nuclei were stained with primary antibodies
      for androgen or vitamin D receptors and secondary fluorescein isothiocyanate
      (FITC) labeled antibodies and propidium iodide respectively, to quantitative
      receptor expression and DNA content by flow cytometry. RESULTS: Androgen receptor
      positive nuclei ranged from 16-66 per cent in the IDC tumours as compared to 36
      67 per cent in the benign tumours. Based on flow cytometric comparison of AR
      expression in AR positive and negative cell lines established earlier, 24 of 28
      tumours from postmenopausal women were AR positive compared to all benign tumours
      and 32 of 33 tumours from pre-menopausal patients. Vitamin D receptor positive
      nuclei ranged from 14-89 and 2-75 per cent in IDC and benign tumours,
      respectively. All pre- or post-menopausal tumours were VDR positive as compared
      to 10 of 15 benign tumours that were VDR positive. No correlation was seen
      between nuclear androgen and vitamin D receptor expression of the IDC or benign
      tumours. There was a positive correlation between per cent of receptor positive
      nuclei and antigen density as measured by ratio of the mean log fluorescence
      channel value (MFC). No statistically significant correlation was found between
      nuclear receptor expression (per cent positive nuclei or antigen density) with
      that of tumour stage, lymph node status, tumour grade, patient age or menopausal
      status. INTERPRETATION & CONCLUSION: There was no significant correlation between
      androgen or vitamin D receptor expression and clinical findings. The expression
      of AR and VDR and the antigen density in the nuclei of the archival breast tumour
      samples were highly variable because of the tumour heterogeneity. Future studies
      with fresh biopsy samples of tumour on AR and VDR levels and their up- or down
      regulation may be useful while stratifying the patients for hormonal therapy.

PMID- 16567873
TI  - Prevalence & phenotypic expression of sopB gene among clinical isolates of
      Salmonella enterica.
AB  - BACKGROUND & OBJECTIVE: Salmonella induced enteritis is a complex phenomenon
      involving a number of pathogenic factors. Type III secretions play a central role
      in the development of Salmonella induced enteritis. One such Type III secretion
      protein is Salmonella outer proteinB (SopB). Reports on the prevalence of this
      gene among different serovars of Salmonella of Indian origin appears to be
      lacking. The present investigation reports on the prevalence of sopB gene and its
      phenotypic expression (SopB protein) among different serovars of Salmonella
      enterica isolated from man and animals. METHODS: A total of 50 isolates of S.
      enterica belonging to 11 serovars isolated from cases of enteric infection in
      man, birds and animals were tested for the presence of sopB gene by polymerase
      chain reaction (PCR) using its specific primers. The in vitro phenotypic
      expression of SopB protein was detected by dot-ELISA using anti-SopB serum.
      RESULTS: All the 50 isolates of S. enterica belonging to 11 were found to carry
      sopB gene irrespective of their serovars like Typhimurium, Enteritidis,
      Gallinarum, Choleraesuis, Virchow, etc., and source of isolation. Of these, 41
      isolates were found to express sopB gene phenotypically as detected by dot- ELISA
      using anti-SopB serum. Of the different serovars, all but Gallinarum expressed
      Sop B protein phenotypically in vitro. INTERPRETATION & CONCLUSION: Our findings
      indicated that sopB gene was wildely distributed and conserved among Salmonella
      irrespective of their serovars and source of isolation. Further work need to be
      done to study the factors associated with the phenotypic expression of this gene.

PMID- 16567874
TI  - High fertility among scheduled tribes of Madhya Pradesh.

PMID- 16567875
TI  - Which hantaviruses in India ?

PMID- 16567876
TI  - Tuberculosis control in Latvia: integrated DOTS and DOTS-plus programmes.
AB  - From 1991 until the end of 1998, the number of patients with tuberculosis in
      Latvia increased 2.5 times with a simultaneous increase of drug resistant and
      multidrug resistant tuberculosis (MDR-TB). Descriptive analysis of different TB
      programme services, activities and strategies including Directly Observed Therapy
      Short-course (DOTS) for tuberculosis and treatment of MDR-TB, were performed.
      Data from the state tuberculosis registry, drug resistance surveillance, and the
      national MDR-TB database were used. The state-funded national tuberculosis
      control programme (NTAP, Nacionala Tuberkulozes Apkarodanas Programma), based on
      WHO recommended DOTS strategy, was introduced in Latvia in 1996. The NTAP
      includes TB control in prisons. Treatment of MDR-TB using second line drugs was
      started in 1997. Cure rates for TB patients increased from 59.5% in 1996 to 77.5%
      in 2003. Between 1996 and 2003, more than 200 patients began MDR-TB treatment
      each year, and the cure rate was between 66% and 73%. Numbers of MDR-TB patients
      were reduced by more than half during this period. Treatment results including
      MDR-TB reached the WHO target, with cure rates 85% of newly diagnosed patients.
      These results demonstrate that MDR-TB treatment and management using the
      individualised treatment approach can be effectively provided within the overall
      TB programme on a national scale, to successfully treat a large number of MDR-TB
      patients. Rapid diagnostic methods combined with early intensified case finding,
      isolation and infection control measures could decrease transmission of TB and
      MDR-TB in hospitals and in the community. Highly important that MDR-TB management
      follows WHO recommendations in order to stop creating drug resistance to first
      and to second line drugs.

PMID- 16567877
TI  - Epidemiology and response to the growing problem of tuberculosis in London.
AB  - As in other countries with low tuberculosis incidence, tuberculosis in England
      and Wales tends to be concentrated in some subgroups of the population, and is
      mainly a problem in large cities. In 2003, almost half of all tuberculosis cases
      reported in England and Wales were from London, where the incidence was almost
      five times higher than in the rest of England and Wales. While the highest
      proportion of cases occur in foreign born patients, evidence from a large
      outbreak of drug resistant tuberculosis points to ongoing active transmission
      among marginalised groups including homeless people, hard drug users, and
      prisoners. Increasing rates of disease and levels of drug resistance, combined
      with a concentration of disease in hard-to-reach risk groups now present a major
      challenge to tuberculosis control in the city. To respond to the changing
      epidemiology observed in recent years, treatment and control services are being
      reconfigured, surveillance has been improved with the implementation of the
      London TB register, and the utility of mobile digital x ray screening for at risk
      populations such as homeless people and prisoners is being evaluated. However,
      tuberculosis in London is not yet under control and more needs to be done.
      Services must adapt to the needs of those groups now most affected. This will
      require continued improvements to surveillance and monitoring, combined with
      improved access to care, better case detection, rapid diagnosis and active social
      support for people undergoing treatment.

PMID- 16567878
TI  - Tuberculosis outcome monitoring--is it time to update European recommendations?
AB  - We discuss tuberculosis treatment outcome monitoring and the adherence of
      countries in the WHO European Region to modifications introduced in 2001 to
      enhance inter-country comparability. Outcomes for definite pulmonary tuberculosis
      cases were compared for cases reported in 2001 and 2000. Reporting was considered
      complete if 98% or more of cases originally notified had outcome reported. In
      both years, maximal period of observation was 12 months from start of treatment.
      In 2000, countries reported outcome as 'cured', 'completed', 'died', 'failed',
      'defaulted', 'transferred' and 'other, not evaluated' for cohorts of new and
      retreated cases. In 2001, following changes, countries were also requested to
      monitor cases with unknown treatment history and two outcome categories were
      added--'still on treatment' and 'unknown'. Of 42 countries reporting outcomes in
      2001, 74% (31) had nationwide, complete data, up from 50% (19/38) in 2000. Twelve
      of 21 countries that reported on observation period complied with that
      recommended. 'Defaulted' and 'transferred' were applied interchangeably with
      'unknown'. Among new cases, 'still on treatment' was used by 15/31 countries
      (range: 1%-15%). 'Failed' was rarely recorded in western European countries
      (<1%). European tuberculosis outcome monitoring should include all definite
      pulmonary cases, applying the standard period of observation and revised
      categories, and preferably reported using individual data.

PMID- 16567879
TI  - BCG in Finland: changing from a universal to a selected programme.
AB  - In Finland, all newborns are currently offered BCG vaccination, and the national
      coverage is over 98%. The annual incidence of tuberculosis is low, at 6.6/100,000
      in 2004 and has been steadily declining in recent years. Finland differs from the
      other Nordic countries in that the majority of cases are detected in people aged
      65 and over in the indigenous population, and only a smaller proportion (12%)
      detected in immigrants. The high incidence of TB and MDR TB in neighbouring
      countries has raised concern, but no increase in TB detected in Finnish-born
      citizens has been seen. A decision has been made to change from mass BCG
      vaccination to targeting risk groups.

PMID- 16567880
TI  - Selective BCG vaccination in a country with low incidence of tuberculosis.
AB  - In 1975 the BCG vaccination policy in Sweden changed from routine vaccination of
      all newborn infants to selective vaccination of groups at higher risk. This
      report aims to evaluate the present BCG policy, with focus on the tuberculosis
      situation in Sweden during the period from 1989 to 2005. The population structure
      in Sweden has changed, with increasing numbers and proportions of people who were
      born outside Sweden, especially in countries with high prevalence of
      tuberculosis. BCG vaccination coverage fell from more than 95% before 1975 to
      less than 2% in 1976 to 1980, and then again increased to around 16%
      (corresponding to about 88% of the risk group recommended for vaccination). The
      increasing proportion of foreign born tuberculosis patients among all
      tuberculosis cases of illness in Sweden, and the high age-specific incidence of
      tuberculosis in the childbearing age groups in the foreign-born population,
      indicate the need to continue selective vaccination of children in families
      originating from countries with high tuberculosis incidence. The cumulative
      incidence of tuberculosis in the 30 cohorts born in Sweden after 1974 and
      observed to the end of 2004 was estimated at 0.5 cases per 100 000 person-years.
      Sweden still has one of the lowest incidences of tuberculosis in the world, which
      means a minimal average risk of infection for the majority of children born to
      Swedish parents. The observed increase of tuberculosis in 2005, partly attributed
      to an outbreak at a day nursery, is a reminder of the serious consequences of
      delayed diagnosis. Intensified active case finding is the most important action
      to prevent childhood tuberculosis, by means of eliminating the sources of
      infection to prevent transmission to the child population. Early detection and
      treatment of infected children is necessary to prevent development of serious
      disseminated tuberculosis.

PMID- 16567881
TI  - Prospects for the BCG vaccination programme in France.
AB  - Until recently, the French BCG vaccination programme consisted of a mandatory BCG
      vaccination before children started at daycare centres, and of re-vaccination of
      tuberculin-negative children. A re-assessment of this programme has been
      undertaken in recent years. It has led in 2004 to the discontinuation of all
      revaccinations and post-vaccination tuberculin tests except those post
      vaccination tuberculin tests performed as part of a diagnosis of tuberculosis
      infection or disease or of the follow-up of health or social workers for whom BCG
      vaccination remains mandatory. Based on an estimate of the epidemiological impact
      of either selective vaccination of high risk children or discontinuation of BCG
      vaccination, and taking into account the risk-benefit balance that can be made of
      the two options, the Conseil Superieur d'Hygiene Publique de France (CSHPF,
      national high committee of public hygiene) has recommended a change to selective
      vaccination. However, the committee has proposed the strengthening of other
      control measures aimed at decreasing the risk of infection for children, as a pre
      requisite to the implementation of this strategy. This position is made more
      complex by the withdrawal of the multipuncture technique in early 2006,
      previously used in France in more than 90% of BCG primary vaccinations.

PMID- 16567882
TI  - European survey of BCG vaccination policies and surveillance in children, 2005.
AB  - In 2005, all 25 EU countries, as well as Andorra, Bulgaria, Norway, Romania and
      Switzerland, participated in a survey on BCG vaccination in children. BCG was
      recommended nationally for children under 12 months in 12 countries, in older
      children in five countries and in children at risk (from origin, contact or
      travel) in 10 countries. Seven countries did not use BCG systematically.
      Revaccination was practised in four countries. In countries with universal
      vaccination, BCG coverage was high (83.0% to 99.8%). TB cases commonly occurred
      in vaccinated children (at least 30%-98% in five countries using universal or
      high-risk approach). Disseminated infection due to BCG was rarely reported in
      recent years (0-1/100 000 vaccinated). There is a wide variation among BCG
      recommendations in Europe, and nearly half the countries surveyed were
      considering revisions, at a time when the European Centre for Disease Prevention
      and Control (ECDC) is advocating for harmonised vaccine strategies. Data on
      monitoring of BCG coverage in target groups is important but often lacking in
      Europe. Information on BCG status and eligibility should be collected routinely
      through TB case notification. The incidence of severe adverse effects of BCG in
      children should be monitored. Given lack of evidence to its efficacy,
      revaccination should be discontinued.

PMID- 16567883
TI  - Tuberculosis and BCG in Europe.

PMID- 16567885
TI  - Listening to music decreases need for sedative medication during colonoscopy: a
      randomized, controlled trial.
AB  - BACKGROUND: Music played during endoscopic procedures may alleviate anxiety and
      improve patient acceptance of the procedure. A prospective randomized, controlled
      trial was undertaken to determine whether music decreases the requirement for
      midazolam during colonoscopy and makes the procedure more comfortable and
      acceptable. METHODS: Patients undergoing elective colonoscopy between October
      2003 and February 2004 were randomized to either not listen to music (Group 1;
      n=40) or listen to music of their choice (Group 2; n=38) during the procedure.
      All patients received intravenous midazolam on demand in aliquots of 2 mg each.
      The dose of midazolam, duration of procedure, recovery time, pain and discomfort
      scores and willingness to undergo a repeat procedure using the same sedation
      protocol were compared. RESULTS: Patients in Group 2 received significantly less
      midazolam than those in Group 1 (p=0.007). The pain score was similar in the two
      groups, whereas discomfort score was lower in Group 2 (p=0.001). Patients in the
      two groups were equally likely to be willing for a repeat procedure. CONCLUSION:
      Listening to music during colonoscopy helps reduce the dose of sedative
      medications and decreases discomfort experienced during the procedure.

PMID- 16567886
TI  - Utility of hydrogen breath tests in diagnosis of small intestinal bacterial
      overgrowth in malabsorption syndrome and its relationship with oro-cecal transit
      time.
AB  - BACKGROUND: Small intestinal bacterial overgrowth (SIBO), which may result from
      intestinal stasis, is common in malabsorption syndrome (MAS). Quantitative
      culture of upper gut aspirate is used as a gold standard for the diagnosis of
      SIBO. Studies on diagnosis of SIBO using non-invasive hydrogen breath tests are
      contradictory. METHODS: 83 patients (age 35 [14-70] y; 50 men) with MAS due to
      various causes were investigated for SIBO using quantitative culture of upper gut
      aspirate obtained using a special endoscopic catheter and glucose and lactulose
      hydrogen breath tests (GHBT, LHBT). Sustained elevation in breath hydrogen of 12
      ppm above basal and two separate peaks (one due to SIBO and the other from colon)
      were diagnostic of SIBO in GHBT and LHBT, respectively. Oro-cecal transit time
      (OCTT) was estimated using LHBT in 71 patients. RESULTS: Thirty two of 81 (39.5%)
      patients with MAS had SIBO on culture (>or= 10(5) CFU/mL). Using aspirate culture
      as the gold standard, sensitivity, specificity, positive and negative predictive
      values and diagnostic accuracy of GHBT to diagnose SIBO were 44%, 80%, 62%, 67%
      and 65%, respectively; the corresponding values for LHBT were 31%, 86%, 62%, 54%
      and 55%, respectively. OCTT in patients with SIBO diagnosed on GHBT and/or
      aspirate culture (n=58) was longer than in those without (170 [60-250] vs. 120
      [50-290] min, p=0.02); of others, 7 were hydrogen non-producers and in 6 OCTT
      could not be assessed due to sustained early peak because of SIBO. CONCLUSIONS:
      GHBT and LHBT are highly specific but insensitive for diagnosis of SIBO in MAS;
      OCTT is longer in patients with MAS and SIBO than in those without.

PMID- 16567888
TI  - Tumor necrosis factor-alpha gene promoter polymorphism in Iranian patients with
      chronic hepatitis B.
AB  - BACKGROUND: Clearance of hepatitis B virus (HBV) infection requires a good host
      immune response. Cytokines like tumor necrosis factor-alpha (TNF- alpha) may play
      a role in such immune response. Genetic changes in TNF-a gene promoter region are
      known to influence TNF- alpha expression. We therefore studied the role of one
      such mutation in chronic HBV infection. METHODS: Presence of -308 G/A
      polymorphism in the promoter region of TNF- alpha gene was looked for in 100
      patients with chronic HBV infection, 91 subjects with spontaneously recovered HBV
      infection and 89 healthy controls, using a PCR-RFLP method. RESULTS: Variant
      alleles (A/A or A/G) were found in 22 of 100 (22%) patients with chronic HBV
      infection, 21 of 91 (23%) subjects with spontaneous HBV clearance and 14 of 89
      (15.7%) control subjects (p=ns for inter-group comparisons). CONCLUSION: TNF-
      alpha promoter polymorphism -308A is common in Iranian population, but has no
      association with development of chronic HBV infection.

PMID- 16567887
TI  - Analysis of patients listed for liver transplantation in Shiraz, Iran.
AB  - AIM: To analyze records of patients listed for liver transplantation (LT) at our
      hospital, the first and the largest LT center in Iran. METHODS: We analyzed
      medical records of patients aged 14 years or older, who were listed for LT for
      chronic liver disease between 1994 and 2004. Outcome was determined from records
      or follow-up data. RESULTS: Among the 480 patients (mean age 39 [SD 13] years;
      327 [68.1%] men) listed for LT, common causes of cirrhosis were cryptogenic (143;
      29.9%) and hepatitis B (127; 26.5%). Child-Turcott-Pugh (CTP) class distribution
      of these patients was: A - 37 (7.7%), B - 258 (53.7%) and C - 185 (38.6%). Mean
      (SD) follow-up duration was 11.4 (11.8) months (range 1-108). One hundred and
      four (21.7%) patients received LT and 173 (36%) died while awaiting LT. CTP class
      influenced 1-year (90%, 73% and 55% in class A, B and C, respectively) and 2-year
      (84%, 48% and 25%, respectively) survival rates. MELD score also influenced
      survival. Survival was better in patients who underwent LT than in those who
      continued on the waiting list (p< 0.01). CONCLUSION: Only about one-fifth of
      patients listed for LT in Iran received LT and a large proportion died without
      LT.

PMID- 16567889
TI  - External duodenal fistula following closure of duodenal perforation.
AB  - AIM: Retrospective analysis of experience with management of external duodenal
      fistula (EDF) without using total parenteral nutrition (TPN). METHOD: Medical
      records of 31 patients with EDF following closure of duodenal ulcer perforation,
      treated over a 7-year period (1994-2001), were studied. Twenty-one patients (68%)
      had evidence of sepsis at presentation or during the course of treatment. None
      could afford TPN for optimum time. All patients received hospital-based enteral
      nutrition through nasojejunal tube, besides supportive medical treatment and/or
      surgery. Peritonitis or failure to insert nasojejunal tube for enteric
      alimentation led to early surgery. RESULTS: Two patients died of septicemia and
      multi-organ failure within 48 hours of admission. Fourteen patients (48.3%)
      initially received conservative treatment (Group I); six of them later required
      surgery. Fifteen patients (51.7%) underwent early surgery due to peritonitis
      (n=9) or failure to establish enteral feeding (n=6) (Group II); wound infection,
      intra-abdominal abscess and septicemia were more common in these patients than
      those in Group I. Survival rate was higher in Group I than in Group II (86%
      versus 40%; p< 0.05). Septicemia and gastrectomy were the independent factors
      associated with high mortality. CONCLUSIONS: EDF can be satisfactorily managed
      without TPN. Successful placement of enteral feeding line, supportive treatment
      and delayed surgery can achieve survival in 85% of patients. Minimum intervention
      is recommended when early surgery is performed in peritonitis or to establish
      enteral feeding line.

PMID- 16567890
TI  - The case for Helicobacter pylori eradication in India: sensationalism, skepticism
      and scientific salesmanship.

PMID- 16567891
TI  - Helicobacter pylori infection in India: the case against eradication.

PMID- 16567892
TI  - Nodular liver in a chronic alcoholic.

PMID- 16567893
TI  - Agenesis of the dorsal pancreas (ADP) and pancreatitis - is there an association?
AB  - Agenesis of the dorsal pancreas (ADP) is a rare congenital anomaly. We describe
      four patients with ADP presenting with acute pancreatitis. One patient had
      diabetes mellitus and another had malrotation of duodenum as an additional
      feature. All patients improved on conservative management.

PMID- 16567894
TI  - Laparoscopic jejuno-jejunostomy for afferent loop stasis following truncal
      vagotomy with posterior gastro-jejunostomy for pyloric stenosis.
AB  - A 47-year-old man presented with epigastric pain relieved by bilious vomiting
      since one month. He had undergone truncal vagotomy with posterior
      gastrojejunostomy for benign gastric outlet obstruction 2 years ago. Endoscopy
      showed distension and stasis in the afferent loop, bile gastritis and
      esophagitis. Laparoscopic Braun jejunojejunostomy relieved his symptoms.

PMID- 16567896
TI  - Small intestinal adenocarcinoma in Peutz-Jeghers syndrome.
AB  - Peutz-Jeghers syndrome (PJS) is characterized by intestinal hamartomatous
      polyposis (usually affecting the jejunum) and mucocutaneous melanin spots. Though
      malignant changes are not common, PJS can predispose to carcinoma in the GI tract
      and elsewhere. We report a 25-year-old man with PJS who developed small
      intestinal adenocarcinoma and presented with small bowel obstruction due to
      jejuno-ileal intussusception.

PMID- 16567895
TI  - Pericardial effusion following esophageal variceal sclerotherapy.
AB  - We report a 37-year-old man with portal cavernoma who developed pericardial
      effusion two weeks following sclerotherapy for esophageal varices. It responded
      to conservative management.

PMID- 16567897
TI  - Successful closure of spontaneous esophageal perforation (Boerhaave's syndrome)
      by endoscopic clipping.
AB  - Endoscopic clips have been used mainly for control of gastrointestinal (GI)
      bleeding and occasionally for closure of GI perforations. However, closure of
      spontaneous esophageal perforation (Boerhaave's syndrome) by clipping has not
      been reported. We described successful non-surgical closure of spontaneous
      esophageal perforation by endoscopic clipping in a patient with bilateral
      pyopneumothorax and septicemia.

PMID- 16567898
TI  - Fatal isoflurane hepatotoxicity without re-exposure.
AB  - Isoflurane is less hepatotoxic than its predecessors, halothane and enflurane. We
      present a 68-year-old man who developed fulminant and fatal hepatic necrosis two
      days after open cholecystectomy done under isoflurane anesthesia. Laboratory
      findings included grossly elevated transaminases and bilirubin and prolonged
      prothrombin time. Serological studies were negative for viral hepatitis.
      Postmortem examination demonstrated centrilobular necrosis of liver.

PMID- 16567899
TI  - Choriocarcinoma - a rare association with squamous cell carcinoma of esophagus.
AB  - Extragenital choriocarcinoma involving the gastrointestinal tract is rare. We
      report a 60-year-old woman with squamous cell carcinoma of esophagus with a
      choriocarcinomatous focus. She was palliated with chemotherapy and an
      endoprosthesis.

PMID- 16567900
TI  - Diagnostic value of gall bladder wall thickness in patients with ascites.

PMID- 16567901
TI  - Anti-HCV IgM as predictor of response to interferon therapy in schistosomal
      patients with chronic hepatitis C.

PMID- 16567902
TI  - Prevalence of Helicobacter pylori amongst expatriates from the Indian
      subcontinent in Southeast Asia.

PMID- 16567903
TI  - Severity and extent of ulcerative colitis: role of C-reactive protein.

PMID- 16567905
TI  - Association of Guillain-Barre syndrome and hepatitis E infection.

PMID- 16567904
TI  - Follow up of patient with totally resected gastric stromal tumor.

PMID- 16567906
TI  - Adult T-cell leukemia blast crisis in a patient with acute liver failure.

PMID- 16567907
TI  - Pancreatic lymphoma: atypical imaging findings.

PMID- 16567908
TI  - Endoscopic ultrasound features of biliary ascariasis.

PMID- 16567909
TI  - National rural health mission.

PMID- 16567910
TI  - Neonatal nosocomial infections in Bahrami Children Hospital.
AB  - OBJECTIVE: Nosocomial infections are one of the most important causes of
      mortality and morbidity in hospitals. These are major public health problems
      worldwide, but particularly in developing countries. These infections have the
      most common frequency in pediatric hospitals-especially in neonatal wards- second
      to burn hospitals. In the present study, neonatal nosocomial infections have been
      reviewed in Bahrami Children Hospital from fall of 1999 through fall of 2004.
      METHODS: Nosocomial infected patients were defined as all patients who were
      neither infected not were in incubation period at the admission time and had
      positive culture after third day of admission. The incidence of nosocomial
      infections computed as infections per 100 hospital discharges and infections per
      100 hospital days. Chi square test was used for comparison of rates. RESULTS:
      Fifty-two patients had been diagnosed having nosocomial infections. NICU
      (Neonatal Intensive Care Unit) showed the highest portion of infections (40%)
      followed by neonatal surgery ward (35%) and neonates ward (25%). Frequencies of
      nosocomial infection by site were as follows: eyes (27%), septicemia, surgical
      wounds and location of drain or catheter (each one 21%), CSF (7%) and urinary
      (2%). The most common pathogenic organisms were Enterobacter (27%), aurues
      Staphilococcus (21%), Klebsiella (18%), E.coli (14%) and epidermis Staphilococcus
      (9%). Total number of hospitalized patients was 5990 and total number of
      hospitalized days was 39,095 in the five years. Infections per 100 hospital
      discharges and 100 hospital days by service were as follows, respectively: NICU
      (2.9, 0.26), neonatal surgery (1.7, 0.18) and neonates (0.3, 0.06). The
      differences were significantly meaningful (p value< 0.001). CONCLUSION: These
      findings provide useful information for future surveillance in association with
      prevention programs. Subsequently, surveillance should be focused on high-risk
      patients in intensive care unit and/or who have undergone surgery and invasive
      procedures.

PMID- 16567911
TI  - Clinical profile and natural history of children with HIV infection.
AB  - OBJECTIVE: As the HIV infection spreads in India, increasing number of children
      are affected. We report the clinical manifestations, the laboratory parameters
      and follow up of these children. METHODS: We reviewed case records of all
      children diagnosed as pediatric HIV infection since 1995 in our department at a
      tertiary care hospital in north India. Since September 1999, all children with
      HIV infection registered in our clinic were prospectively followed up. Complete
      clinical and laboratory evaluation was performed at baseline and thereafter
      children were followed up. The children were managed according to standard
      treatment guidelines. RESULTS: 109 children (82 boys, 27 girls) were diagnosed to
      have HIV infection. The median (range) age at presentation was 48 months (range:
      0.75 months-180 months). Eighty one (74.3%) children acquired the infection
      vertically. Ninety-one (83.5%) children were symptomatic at time of presentation.
      The common symptoms in the former were failure to thrive (81.3%), recurrent fever
      (73.6%), diarrhea (50.5%) and recurrent or persistent pneumonia (44%). All
      children had poor nutritional status at baseline. Of the 67 children who followed
      up, 36 were receiving antiretroviral drugs (32 received 3 drugs), while families
      of 31 children did not opt for antiretroviral therapy. Children receiving
      antiretroviral therapy showed improvement in nutritional parameters. CONCLUSION:
      Majority of children with HIV infection presented with various clinical
      manifestations, poor nutritional status and immunosuppression. Administration of
      nevirapine based antiretroviral therapy leads to improvement in growth and immune
      restoration.

PMID- 16567912
TI  - Prevalence of pediatric HIV in New Delhi.
AB  - OBJECTIVE: This study was carried out to determine the prevalence of HIV
      infection in North India, as there are scanty reports from this part of India.
      METHODS: The prevalence of HIV infection was determined by serological tests for
      HIV antibodies in children born to a seropositive mother or suffering from
      chronic diarrhea, failure to thrive or disseminated tuberculosis. RESULTS: One
      hundred and twelve children were tested of which ten were seropositive (8.9%).
      This included six children born to seropositive mother (22%), two with chronic
      diarrhea (4%), one with failure to thrive (5%) and one child with disseminated
      tuberculosis (6.6%). CONCLUSION: HIV infection is an emerging reality in New
      Delhi. A clinically directed screening can help detect more cases.

PMID- 16567913
TI  - Magnesium therapy in birth asphyxia.
AB  - OBJECTIVE: Glutamate plays a critical role in the hypoxic ischaemic neuronal
      death. Two mechanisms of glutamate- induced neuronal death have been identified.
      One is rapid cell death that occurs in minutes and the second is delayed cell
      death that occurs over hours and is initiated principally by the activation of
      the N-methyl D-Aspactate (NMDA) receptor. Magnesium (Mg) is an NMDA receptor
      blocker. Systemic administration of Mg after a simulated hypoxic ischaemic insult
      has been shown to limit neuronal injury in several animal models. However, before
      embarking on to the use of Mg for neuronal protection in the human neonate it is
      important to study the safety and side effects of Mg administration. METHODS:
      Forty terms, appropriate for gestational age babies with severe birth asphyxia (1
      min Apgar score < 3 and 5 min Apgar score < 6), were randomly assigned to either
      the study group or the control group. Infants in both groups were treated as per
      unit protocol except that babies in the study group received intravenous
      injection of magnesium sulphate 250 mg/kg within half an hour of birth and
      subsequently 125 mg/kg at 24 and 48 hours of life. RESULTS: The mean cord blood
      serum Mg levels were 0.78 (+/- 0.047) mmol/L in the control group and 0.779(+/
      0.045) mmol/L in the study group. The serum Mg levels at 3, 6, 12, 24, 48 and 72
      hours of life were 1.87(+/-0.6), 1.65(+/-0.059), 1.468 (+/-0.91), 1.881 (+/-
      0.053), 1.916 (+/- 0.053) and 1.493 (+/- 0.084) mmol/L respectively in the study
      group. All these values were significantly higher than those obtained in the
      control group (p< 0.001). No significant alterations in heart rate, respiratory
      rate, oxygen saturation and mean arterial pressure were seen, following magnesium
      infusion with either 250 mg/kg or 125 mg/kg dose. The serum Mg levels in the
      study group ranged between 1.493 (+/- 0.084) and 1.916(+/-0.053) mmol/L, which
      are considered to be in the neuroprotective range. CONCLUSION: Injection MgSO4
      administered in a dose of 250 mg/kg and 125 mg/kg as an intravenous infusion is
      safe and the Mg levels obtained are in the range considered to be
      neuroprotective.

PMID- 16567914
TI  - Psychosocial impact and personality predictors of coherence feeling among girls
      with acne.
AB  - OBJECTIVE: The extent to which acne influences the emotional life of adolescents
      is a matter of discussion; but people with acne are prone to emotional and
      psychological disturbances. METHODS: 54 adolescent girls with acne were studied
      for their personality variables that are related to high coherence. Sense of
      coherence, e.g. meaningfulness of life, is crucial to cope successfully with
      stressors of living: it expresses the belief that a high probability exists that
      things will work out as well as can reasonably be expected. 58 adolescent girls
      without acne were in the control group. RESULTS: Neuroticism (anxiety level) was
      the first predictor of the sense of coherence measure for girls with acne,
      explaining 19% of the variance. Extraversion was the next predictor, explaining
      an additional 2 3% of the variance and psychoticism was the third predictor,
      explaining together 27% of the variance. There was a lack of difference between
      groups with respect to other personality variables. CONCLUSION: These predictors
      have to be taken into consideration while treating adolescents acne.
      Dermatologists, pediatricians and other physicians treating adolescents' acne
      should be familiar with emotional and psychosocial disturbances that accompany
      acne in order to effectively assist these patients.

PMID- 16567915
TI  - Ultrasound guided hydrostatic reduction in the management of intussusception.
AB  - OBJECTIVE: A case series study was conducted for two years from 01 June 2002 to
      01 June 2004 to study the efficiency of ultrasound guided hydrostatic reduction
      in the management of intussusception in children. METHODS: A total of 25 patients
      who underwent the procedure were evaluated. All the patients were diagnosed by
      High Resolution Ultrasonography (HRUSG). Continuous monitoring of the progress of
      reduction during the procedure was done by HRUSG. 500-1000 ml (average 600 ml) of
      normal saline was used. RESULTS: 24 out of 25 (96%) intussusceptions were
      successfully reduced. Average time taken was 15 minutes. All the patients were
      reviewed after 24 hrs for recurrence. None of them showed recurrence within 24
      hrs. No complications were observed. CONCLUSION: The study concludes that
      ultrasound guided hydrostatic reduction is a safe, simple and effective method
      for treatment of intussusception in children.

PMID- 16567916
TI  - Retroperitoneal teratomas in children.
AB  - OBJECTIVE: This paper aims to highlight the clinical features, investigations and
      treatment of retroperitoneal teratomas condition. METHODS: 12 patients (8 females
      and 4 males, age range-2 months to 14 yrs) of retroperitoneal teratoma admitted
      to the department of Pediatric Surgery, King George Medical University, Lucknow
      between 1980 and 2004 were studied. Investigations included hematology, plain X
      ray of the abdomen, intravenous urography, ultrasound, computerised tomography
      (CT) of the abdomen (after 1990, 8 patients) and serum alpha-fetoprotein assay
      (after 1991, 6 patients, preoperatively). All patients underwent surgery. Serum
      alpha-fetoprotein assay was used during follow-up to detect recurrence. RESULTS:
      Majority of the tumors were left pararenal in location. In two patients there was
      bilateral involvement. In all except one, the tumor could be excised easily
      preserving the kidneys. In one child with a massive cystic tumor with bilateral
      involvement, the tumor was marsupialised in the first stage and excised
      subsequently. One child died postoperatively, the other 11 children are well and
      there has been no tumor recurrence on follow-up. CONCLUSIONS: Retroperitoneal
      teratomas are uncommon lesions in children mostly arising in close relation to
      the kidneys. The majority are benign but complete excision is necessary for cure.
      Even large tumors with bilateral involvement of the retroperitoneum can be
      excised while preserving adjacent organs. Serum alpha-fetoprotein assay is a
      reliable method of detecting recurrence.

PMID- 16567917
TI  - Juvenile amyotrophic lateral sclerosis.
AB  - Juvenile amytrophic lateral sclerosis (JALS) is a type of motor neuron disease
      presenting before 25 years of age. It is characterized by a combination of upper
      and lower motor signs. It may be familial or sporadic. We are reporting a
      sporadic case of JALS with onset of symptoms at 4 years of age. Diagnostic
      criteria and a brief review of literature are presented.

PMID- 16567918
TI  - Embryologic preputial sinus remnant mimicking urethral duplication.
AB  - Urethral duplications are rare congenital anomalies. Approximately 200 cases of
      urethral duplications have been reported in literature. We present a seven-year
      old-boy with an embryologic preputial sinus remnant which was mimicking urethral
      duplication. The clinical presentations and embryology of the urethral
      duplication and preputial sinus are discussed.

PMID- 16567919
TI  - Crohn's disease presenting as palatal ulcer.
AB  - Crohn's disease (CD) in children younger than 5 years of age is termed as early
      onset inflammatory bowel disease (EO-IBD). We report a 4 yr 6 mo-old child with
      EO-IBD, who presented with palatal ulcer, an extra intestinal manifestation of
      Crohn's disease as the dominant feature.

PMID- 16567920
TI  - Caroli's disease.
AB  - Caroli's disease is a rare congenital disorder and occasional cases have been
      reported from Japan and other parts of Asia. It comprises of congenital dilation
      of the lower (segmental) intrahepatic bile duct. Cholangitis liver, cirrhosis and
      cholangiocarcinoma are its potential complication. A case of caroli's disease in
      an 8-years-old boy with bilobar involvement of liver, (specially affecting right
      superior lobe) presenting with intermittent abdominal pain, fever and
      hepatosplenomegaly is reported here.

PMID- 16567921
TI  - Hypereosinophilic syndrome.
AB  - Hypereosinophilic syndrome is a leukoproliferative disease characterised by
      sustained overproduction of eosinophils. The three diagnostic criteria for this
      disorder are (1) Eosinophilia of greater than 1500 cells/ml, persisting for
      longer than 6 months, (2) lack of another diagnosis to explain the eosinophilia
      and (3) signs and symptoms of organ involvement. We report a 15-year-old boy who
      was diagnosed as Hypereosinophilic syndrome based on these criteria.

PMID- 16567922
TI  - Childhood primary mesenteric seminoma.
AB  - We report an 11-year-old child who presented with an abdominal lump and was
      diagnosed as having an extragonal primary mesenteric seminoma. Patient was
      treated with 4 cycles of combination chemotherapy cisplatin, etoposide and
      bleomycin; he is now disease free for 2 years. We discuss and review extragonadal
      germ cell tumors arising from the mesentery and their management.

PMID- 16567924
TI  - National rural health mission: training of health functionaries.

PMID- 16567923
TI  - Jarcho-Levin syndrome.
AB  - Jarcho-Levin syndrome is an eponym that represents a spectrum of short trunk
      skeletal dysplasias with variable involvement of the vertebrae and ribs.
      Initially considered to be lethal, it is now accepted as compatible with life in
      its milder presentations. Here are reported two neonates with the lethal variety
      of this syndrome. One neonate had associated anomalies like hydrocephalus,
      hydroureteronephrosis and meningomyelocoele while the other had no additional
      anomalies. Also is reviewed the literature regarding this less understood
      disorder focusing on the applied clinical aspects that have stemmed out from the
      recent molecular research.

PMID- 16567925
TI  - Improvement in Lasegue's sign: an early predictor of recovery in childhood
      Guillain-Barre syndrome.

PMID- 16567926
TI  - Persistent pulmonary hypertension among neonates with sepsis.

PMID- 16567927
TI  - Early onset neonatal sepsis.

PMID- 16567928
TI  - The retina of tyrant flycatchers: topographic organization of neuronal density
      and size in the ganglion cell layer of the great kiskadee Pitangus sulphuratus
      and the rusty margined flycatcher Myiozetetes cayanensis (Aves: Tyrannidae).
AB  - Tyrant flycatchers comprise the largest group of passerine birds of the
      Neotropical region but their retinal organization is unknown. The great kiskadee,
      Pitangus sulphuratus, is categorized as a supreme generalist and utilizes a
      variety of foraging strategies. The rusty margined flycatcher, Myiozetetes
      cayanensis, is partially frugivorous and captures insects in the air. Using
      retinal wholemounts, we described the topographic distribution of density and
      size of neurons lying in the retinal ganglion cell layer in those two species of
      tyrant flycatchers. Maps of neuron distribution showing isodensity contours
      revealed the presence of a pronounced central fovea and a temporal area in both
      species. Both retinal specializations were circumscribed by an inconspicuous
      horizontal visual streak. The highest foveal densities ranged from 48,000 to
      55,000 cells/mm(2) for Pitangus sulphuratus and between 62,000 and 65,000
      cells/mm(2) for Myiozetetes cayanensis. The peak density in the temporal area was
      around 40,000 cells/mm(2) for Pitangus sulphuratus and 46,000 cells/mm(2) for
      Myiozetetes cayanensis. At central, mid-peripheral and peripheral eccentricities,
      perikaryon size varied quite similarly in both species. A cohort of giant retinal
      ganglion cells with perikaryon size > 300 microm(2) was observed at the temporal
      periphery and defines an 'area giganto cellularis' described previously in
      procellariiform seabirds. This specialization is thought to be involved in
      movement detection and could aid the tyrant flycatchers to capture moving prey.
      Functionally, the presence of a fovea associated with a temporal area would allow
      high spatial resolution for capturing insects by the tyrant flycatchers.
      Nonetheless, even though both species exhibit different foraging strategies, they
      shared a similar topographic arrangement of neuronal density in the ganglion cell
      layer. This suggests that the retinal topography did not accompany changes in the
      foraging ecology throughout evolutionary history for these species of tyrant
      flycatchers.

PMID- 16567929
TI  - Cell birth and survival following seasonal periods of cell proliferation in the
      chemosensory epithelia of red-backed salamanders, Plethodon cinereus.
AB  - In addition to the continuous low levels of neurogenesis typical of adult
      vertebrates to replace damaged chemoreceptor cells, red-backed salamanders
      (Plethodon cinereus) experience an up-regulation of chemoreceptor epithelial cell
      proliferation on a seasonal basis. Significantly more cell division occurs in
      late spring than at any other time of the year, and we investigated the fate and
      life span of these newly generated cells. We used 5-bromo-2'-deoxyuridine (BrdU)
      immunocytochemical cell birth dating to examine cell proliferation and cell
      migration in the main olfactory and vomeronasal epithelia of red-backed
      salamanders collected in late spring who were allowed to survive for one hour or
      three, four, 25, 28, 42, 49 and 100 days post-injection. We examined new neuron
      growth in the vomeronasal and olfactory epithelia using antibodies against Growth
      Associated Protein-43 (GAP-43), a protein whose synthesis is up-regulated during
      axon growth. We also tracked apoptosis within both types of chemosensory
      epithelia using terminal deoxynucleotidyl transferase-mediated nick-end labeling
      (TUNEL). BrdU-immunoreactive cells were located extensively throughout the
      vomeronasal epithelia, particularly in the area posterior to the entrance of the
      nasolacrimal duct, not only after three days of survival, but also all of the
      longer experimental survival periods as well; BrdU-ir cells within the olfactory
      epithelia were rarely located after longer survival periods. Salamanders
      collected in late spring displayed extensive GAP-43 labeling in the vomeronasal
      epithelia posterior to the entrance of the nasolacrimal duct, indicating a large
      population of young vomeronasal receptor neurons. Finally, apoptotic cells were
      evident in this same post-nasolacrimal-duct-area of the vomeronasal organ and in
      the olfactory epithelium. We suggest that vomeronasal receptor neurons born in
      late spring function throughout the summer and may be associated with the
      animals' extensive territoriality during that period.

PMID- 16567930
TI  - Dipyridamole plus aspirin: the best regimen for stroke prevention after
      noncardioembolic focal cerebral ischemia.

PMID- 16567931
TI  - Comparison of warfarin versus aspirin for the prevention of recurrent stroke or
      death: subgroup analyses from the Warfarin-Aspirin Recurrent Stroke Study.
AB  - BACKGROUND AND PURPOSE: We performed a combination of prespecified and
      exploratory subgroup analyses to detect any treatment differences among various
      baseline subgroups in the Warfarin-Aspirin Recurrent Stroke Study (WARSS) cohort.
      METHODS: The WARSS compared the efficacy of adjusted-dose warfarin (INR 1.4-2.8)
      to aspirin (325 mg/day) for recurrent ischemic stroke or death within 2 years.
      The effect of warfarin and aspirin was compared among prespecified and
      exploratory subgroups with respect to sociodemographic and vascular risk factors,
      stroke subtype, arterial territory, and infarct topography. Hazard ratios and 95%
      confidence intervals comparing warfarin to aspirin were calculated using Cox
      proportional hazards models. Differences in hazard ratios were tested using
      interaction terms. RESULTS: No treatment differences between warfarin and aspirin
      were found across multiple prespecified subgroups. In a multivariate model,
      warfarin was associated with greater hazard among patients with moderate stroke
      severity (HR 1.63, 95% CI 1.005-2.64, p = 0.047) and a greater benefit among
      those with posterior circulation location without brainstem infarction (HR 0.54,
      95% CI 0.33-0.88, p = 0.013). In post-hoc analyses of the cryptogenic subgroup,
      warfarin was associated with worse outcomes among patients with moderate stroke
      severity and better outcomes among those without baseline hypertension or with
      posterior circulation infarcts sparing the brainstem. CONCLUSIONS: In the WARSS,
      the majority of subgroup analyses showed no benefit of warfarin over aspirin.
      Warfarin benefit was limited to brainstem-sparing posterior circulation infarcts
      and select cryptogenic stroke subgroups. Pending future clinical trial evidence
      to the contrary, antiplatelets are recommended for survivors of noncardioembolic
      stroke.

PMID- 16567932
TI  - Mutations and polymorphisms in genes affecting hemostasis proteins and
      homocysteine metabolism in children with arterial ischemic stroke.
AB  - BACKGROUND: The pathogenesis of thrombosis in childhood seems to be
      multifactorial implicating genetic and environmental factors. AIM: To compare the
      distributions of mutations/polymorphisms in genes affecting hemostasis (factor V
      Leiden - FVL, FV H1298R-FVR2, FII 20210A, b-Fib 455G>A, FXIII V34L, PAI-1 4G, HPA
      1b) or homocysteine metabolism (MTHFR C677T, MTHFR A1298C) among 90 children with
      arterial ischemic stroke (AIS) and 103 controls, and to associate the carriage of
      these mutations/polymorphisms with their corresponding proteins in children with
      AIS. RESULTS: AIS was more frequent in boys (p < 0.01). No studied
      mutation/polymorphism was found to be a risk factor for AIS, except for FVL [odds
      ratio 4.2 (95% CI 1.5-12.1)], the presence of which was even higher in 31
      children with congenital AIS [odds ratio 6.82 (95% CI 2.0-22.8)]. FVL carriers
      had an odds ratio of 5.76 (95% CI 1.6-6.4) when FVR2 was absent. In thrombosed
      children, activated protein C resistance, prothrombin and fibrinogen levels were
      higher in the presence of FVL, FII20210A or b-Fib 455G-->A, respectively. Double
      heterozygotes in both MTHFR C677T and A1298T or homozygotes in one had
      significantly elevated homocysteine levels. CONCLUSION: Except for FVL, no
      definite conclusion could be reached regarding the involvement of the studied
      mutations/polymorphisms in childhood AIS.

PMID- 16567933
TI  - 30-day survival and rehospitalization for stroke patients according to physician
      specialty.
AB  - BACKGROUND AND PURPOSE: Stroke patients appear to have improved outcomes when
      cared for by neurologists, but the mechanism by which improved outcome is
      achieved is unclear. This study compares 30-day cause-specific rehospitalization,
      30-day mortality, and specific processes of care for patients treated by a
      neurologist only, a generalist only, a neurologist and a generalist (i.e.,
      collaborative care), or by another specialist during the index hospitalization.
      METHODS: This study uses Cox regression to analyze claims and enrollment data
      from 44,099 Medicare beneficiaries 65 years of age and older and discharged with
      acute ischemic stroke from 1998 to 2000 in 11 US metropolitan regions. RESULTS:
      Patients seen by neurologists had more severe strokes than patients seen by
      generalists, though patients seen by generalists had more comorbidities. Patients
      seen by neurologists (alone or collaboratively) had a 10 and 16% lower risk of 30
      day mortality, respectively. Patients seen by a neurologist only had a 12% lower
      risk of rehospitalization for infections and aspiration pneumonitis. In contrast,
      patients seen by neurologists had a higher risk of rehospitalization for
      atherosclerotic (cardiovascular and non-acute cerebrovascular) disease. Patients
      seen by neurologists were more likely to be discharged to inpatient
      rehabilitation, had longer lengths of stay, and were more likely to receive
      warfarin after discharge. CONCLUSIONS: Results support the hypothesis that
      neurologists improve outcomes specifically by reducing the potential for
      aspiration (through increased swallowing evaluations) or by improving functioning
      (through use of rehabilitation therapy). Future studies should continue to
      examine the mechanisms by which neurologists may achieve better outcomes in
      stroke care.

PMID- 16567934
TI  - Delayed transient worsening of neurological deficits after ischaemic stroke.
AB  - BACKGROUND: Although the causes of stroke recurrence are well known, no
      particular study deals with the specific issue of late-onset transient worsening
      of the neurological deficit (TWND) after an ischaemic stroke. PATIENTS AND
      METHODS: In this retrospective study the aetiology of the TWNDs in 101 patients
      was compared to the causes of transient ischaemic attacks (TIAs) in 115 patients.
      All patients had a full cardiovascular and neuroimaging examination according to
      current guidelines. An electroencephalogram (EEG) was performed when necessary.
      The diagnosis of inhibitory seizures was retained when the EEG showed periodic
      lateralized epileptiform discharges or intermittent rhythmic delta activities, or
      when the patient developed typical seizures afterwards. RESULTS: Arterial
      hypertension and diabetes were more prevalent vascular risk factors in TWND
      patients. Small-vessel disease and inhibitory seizures were a more frequent cause
      of TWNDs than of TIAs. Extracranial large-vessel disease predominates in TIA
      patients. The global prevalence of cardiac diseases as cause of TIAs and TWNDs
      was the same, although severe ulcerous plaques of the aortic arch and patent
      foramen ovale with atrial septum aneurysm occurred more frequently in TWND
      patients. CONCLUSIONS: The most frequent causes of late-onset TWNDs were
      different from those of TIAs. Apart from repeated neuroimaging of the brain,
      exhaustive cardiac investigations and EEG are mandatory in TWND patients.

PMID- 16567935
TI  - Basal Ganglia-thalamic hemorrhage in young adults: a hospital-based study.
AB  - BACKGROUND: The causes of basal ganglia-thalamic hemorrhage in the young are not
      well established. Therefore, its clinical profile, etiology, and risk factors
      were studied. METHODS: Retrospectively, collected data were evaluated using the
      chi(2) test and logistic regression analysis. RESULTS: Gender differences
      occurred in the clinical profile, risk factors, and etiological spectrum. Large
      hematoma, Glasgow Coma Scale </=10 on admission, and the need for surgical
      intervention occurred significantly more frequently in males. The etiologies
      included vascular anomaly in 13 of 247 enrollees (5.3%), hypertension (80.2%),
      alcoholism/cigarette smoking (4.9%), medical problems (8.5%), and cryptogenic
      causes (5.3%). CONCLUSION: The need for aggressive investigation is suggested in
      normotensive patients, especially in females and those aged below 30 years.

PMID- 16567936
TI  - Direct costs of surgical clipping and endovascular coiling of unruptured
      intracranial aneurysms.
AB  - BACKGROUND: Unruptured intracranial aneurysms can be preventively treated by
      surgical clipping or endovascular coiling. We determined in detail the costs of
      these treatments. METHODS: We included patients who were treated for an
      unruptured aneurysm between 1997 and 2003. Patients coiled in this period were
      matched with clipped patients according to the year of treatment, age and gender.
      Considering clipping and coiling, we compared all pre-admission costs of
      diagnostic procedures, all costs of treatment, and costs during follow-up
      including standard angiographic control examinations at 6 and 18 months after
      coiling. Costs were calculated as the product of the used resources and the costs
      of these resources. RESULTS: The mean price for clipping was EUR 8,865.42 and
      that for coiling EUR 10,370.29. The difference was mainly determined by the
      higher material costs of coiling (EUR 5,300) compared with clipping (EUR 690).
      Costs of clipping were mainly determined by the need for intensive care
      facilities (1.2 days after clipping and 0 days after coiling) and the length of
      hospital stay (10.5 days after clipping and 3.4 days after coiling). After
      bootstrapping the data, costs of coiling were on average EUR 1,553 (95%
      confidence interval: EUR 1,539-1,569) higher than those of clipping. CONCLUSIONS:
      For unruptured intracranial aneurysms, direct in-hospital costs of coiling are on
      average higher than those of clipping, mostly because of the more expensive
      coils.

PMID- 16567937
TI  - Cerebrovascular reserve capacity is preserved in a population-based sample of
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: Type 2 diabetes mellitus (DM2) is associated with an
      increased risk of stroke. DM2 is also associated with cognitive impairments.
      Vascular dysfunction, such as impaired cerebrovascular reserve capacity (CVR),
      may be a determinant of these changes, but previous studies on CVR in DM2 have
      provided variable results in selected populations of patients. We aimed to
      examine CVR in a population-based sample of DM2 patients. METHODS: The CO(2)
      reactivity of the middle cerebral artery was examined using transcranial Doppler
      ultrasonography in 81 DM2 patients and 38 controls. In DM2 patients CVR was
      correlated with diabetic parameters, vascular risk factors and cognitive
      functioning. RESULTS: CVR was similar in patients and controls (51 vs. 49%).
      Within the DM2 group, there was no statistically significant relationship between
      CVR and DM duration, HbA(1c), albuminuria, blood pressure, intima-media thickness
      and cognition. CVR tended to be lower in diabetic patients with retinopathy [46
      vs. 55%, mean difference: -7.9 (confidence interval -18.0, 2.2)]. CONCLUSION: We
      conclude that CVR is not impaired in unselected patients with DM2 and probably
      does not, therefore, play a major role in the aetiology of cognitive impairment.

PMID- 16567938
TI  - Effect of early and delayed recanalization on infarct pattern in proximal middle
      cerebral artery occlusion.
AB  - BACKGROUND: To investigate the effect of early (<6 h) versus delayed (>6 h)
      recanalization on infarct pattern in acute middle cerebral artery (MCA)
      occlusion. METHODS: 35 patients with acute MCA occlusion (M1 segment; symptom
      onset <6 h) were analyzed. Stroke MRI was performed immediately after admission
      (day 0), and on days 1 and 7. In addition, vessel status was assessed within 6 h,
      at 24 h and on day 7. Patients were grouped according to early (</=6 h, n = 10),
      delayed (6-24 h, n = 8) or no recanalization within 24 h (n = 17). Infarct
      patterns between the three subgroups were compared on normalized day 1 diffusion
      weighted imaging (DWI) data. Lesion plots were generated for the three subgroups
      depicting voxel by voxel the relative frequency of infarction. RESULTS: Lesion
      growth was significantly larger in the group without recanalization (125 +/- 100
      cm(3); mean +/- SD) compared to patients with early (41 +/- 42 cm(3); p = 0.02)
      or delayed (47 +/- 45 cm(3); p < 0.05) recanalization. The analysis of infarct
      patterns revealed extensive sparing of peripheral cortical regions in both the
      early and delayed recanalization groups compared to the persistent occlusion
      group. In the early/delayed recanalization groups, cortical involvement was often
      limited to the central MCA territory (i.e. insular region and adjacent cortex, in
      addition to the basal ganglia). The final infarct volume was 80 +/- 71 cm(3) in
      patients with early, 93 +/- 62 cm(3) in those with delayed, and 194 +/- 156 cm(3)
      in those without recanalization. CONCLUSIONS: Delayed recanalization
      significantly limits DWI lesion expansion in patients with proximal MCA occlusion
      and selectively saves peripheral cortical regions. Collateral supply to the
      peripheral MCA territory may be sufficient for an extended period of time.

PMID- 16567939
TI  - Pattern of antibiotic therapy and clinical outcome in acute generalized
      peritonitis in semi-urban and rural Nigerians.
AB  - To determine the pattern of antibiotic therapy and clinical outcome a prospective
      survey of all patients operated on for acute generalized peritonitis was
      undertaken. The male to female ratio was 1.7:1, and the mean age was 27.6 +/-
      18.3 years. Operative findings were typhoid ilea perforation in 75 (38.1%),
      complicated acute intestinal obstruction in 44 (22.3%), complicated and
      uncomplicated acute appendicitis in 34 (17.3%), peptic ulcer perforation in 18
      (9%) and traumatic intestinal injury in 11 (5.6%), representing the majority of
      the patients. A combination of chloramphenicol, gentamicin and metronidazole was
      given to 80 (40.6%), ampiclox, gentamicin and metronidazole to 72 (36.5%),
      ampiclox and gentamicin to 21 (10.6%) and other combinations to 5. A single
      antibiotic was administered in 13 (6.6%), that is clavulanate-amoxicillin,
      ampiclox, and cefuroxime. Antibiotics were changed in 37 patients (18.8%): to
      amoxicillin-clavulanate in 13, cefuroxime in 11, ceftriazone in 7, cefuroxime and
      metronidazole in 4 and amoxicillin-clavulanate and metronidazole in 2 patients.
      Postoperative complications were mainly wound infection in 105 (42.6%), wound
      dehiscence in 33 (16.7%), residual intra-abdominal sepsis in 19 (9.6%), residual
      intra-abdominal abscess in 17 (8.6%), postoperative chest infection in 14 (7%),
      incisional hernia in 11 (5.6%), anaemia in 6, faecal fistula in 5 and there was a
      mortality of 15.7%.

PMID- 16567940
TI  - Examination of a novel, specified local antibiotic therapy through
      polymethylmethacrylate capsules in a rabbit osteomyelitis model.
AB  - Chronic bone and soft tissue suppurations have become more frequent recently due
      to the increasing number of high-energy injuries. There are certain antibiotic
      beads available for local administration, but they cannot always be applied
      specifically against the pyogenic microorganisms. In the present study, a new
      technique of local antibiotic therapy for the treatment of infections is
      described. Polymethylmethacrylate (PMMA) capsules were produced and filled with
      0.1 ml Tazocin (0.02 g piperacillin sodium + 0.005 g tazobactam). The efficacy of
      these Tazocin-filled capsules was examined in vivo using a rabbit osteomyelitis
      model. Chronic osteomyelitis was induced in rabbit tibia by local injection of
      Staphylococcus aureus. The treatment included surgical debridement and
      implantation of Tazocin-containing PMMA capsules into the medullar cavity (n =
      12). Simple surgical debridement with no antibiotic implantation was performed in
      control animals (n = 7). Results were evaluated using microbiological,
      radiological and histological methods 14 weeks after induction of osteomyelitis.
      Eight weeks after the implantation of PMMA capsules, complete physical,
      radiological and histological healing was achieved in 7 animals, initiation of
      the reparative phase was observed histologically in 3 cases and no reparative
      signs were detected in 2 rabbits. In the control group, no significant sign of
      reparation could be seen in any of the cases.

PMID- 16567941
TI  - A phase I study of oral uracil-tegafur prior to weekly intravenous gemcitabine in
      patients with advanced pancreatic cancer.
AB  - BACKGROUND: Gemcitabine is widely accepted as the first-line agent for advanced
      pancreatic cancer. The antitumor cell activity of gemcitabine is higher when
      administered after 5-fluorouracil (5-FU) rather than before 5-FU in an in vitro
      study. The present study was conducted to define the maximum tolerated dose and
      dose-limiting toxicity associated with an oral fluoropyrimidine prodrug that
      combines uracil and tegafur (UFT), given prior to weekly intravenous gemcitabine
      in patients with advanced pancreatic cancer. METHODS: Over a 21-day cycle,
      gemcitabine was given intravenously over 30 min on days 8 and 15, while UFT was
      given orally from days 1 to 14. The dose of UFT used was 400 mg per day, given as
      two doses. The dose of gemcitabine was escalated in a stepwise fashion from 800
      (level 1, n = 3) to 900 mg/m2 (level 2, n = 6) and then to 1,000 mg/m2 (level 3,
      n = 3), such that totally 12 patients received the combination chemotherapy.
      RESULTS: During the first cycle, grade 3 leukopenia was observed in 2 patients at
      dose level 1. Only 1 patient treated at dose level 2 experienced dose-limiting
      toxicity (grade 3 elevated transaminase), including additional patients treated
      at this dose level. No grade 3/4 toxicities occurred in patients treated at dose
      level 3. A significant response was observed in 1 out of 12 patients (8.3%).
      Seven patients (58.3%) had stable disease, while 4 patients (33.3%) showed
      disease progression. CONCLUSIONS: The combination chemotherapy of oral UFT and
      gemcitabine was convenient, well tolerated and may benefit patients with advanced
      pancreatic cancer. Doses recommended for further study of this schedule are
      gemcitabine 1,000 mg/m2 and UFT 400 mg/day.

PMID- 16567942
TI  - Antifungal Activity of Chromolaena odorata (L.) King & Robinson(Asteraceae) of
      Cameroon.
AB  - An aqueous ethanol extract of leaves of Chromolaena odorata and some of its
      fractions were examined for their antifungal properties by dilution methods on
      solid and liquid media, using yeasts and filamentous fungi. Extract and fractions
      inhibit the in vitro growth of Cryptococcus neoformans, Microsporum gypseum,
      Trichophyton mentagrophytes and Trichophyton rubrum with a minimal inhibitory
      concentration range from 62.5 to 500 microg/ml for the extract and from 25 to 100
      microg/ml for fractions. A qualitative chemical analysis of the extract and
      fractions showed the presence of biologically active constituents such as some
      coumarins, flavonoids, phenols, tannins and sterols. No toxic effect was observed
      in mice treated per os with the extract. This study provides a scientific
      confirmation of the use of Chromolaena odorata in traditional medicine.

PMID- 16567943
TI  - Reevaluation of routine invasive strategy versus noninvasive testing following
      uncomplicated ST-elevation myocardial infarction.
AB  - BACKGROUND AND AIMS: While current guidelines recommend a selective invasive
      approach after low-risk ST-elevation myocardial infarction (STEMI) treated by
      thrombolysis, based on noninvasive identification of patients with residual or
      inducible myocardial ischemia, in many instances physicians employ a strategy of
      routine angiography. The present study was undertaken to reexamine the
      correlation between noninvasive testing and coronary angiography in patients
      recovering from uncomplicated STEMI with regard to detection and management of
      residual infarct artery stenosis and to identify patients with multivessel (MVD)
      or high-risk coronary disease. METHODS: We prospectively performed predischarge
      exercise testing (ETT) and myocardial perfusion scintigraphy (MPS) prior to
      routine predischarge coronary angiography in 83/276 consecutive STEMI patients,
      who after treatment with initial and early thrombolysis, were defined as low risk
      by ACC/AHA risk classification. RESULTS: ETT was positive for myocardial ischemia
      in 11/43 (26%) patients with single-vessel disease (SVD) and 11/22 (50%) patients
      with MVD, but normal or nondiagnostic in the remainder. MPS revealed significant
      reversible perfusion defects in 13/40 (32%) patients with SVD and 13/22 (59%)
      patients with MVD. A selective strategy of ETT followed by MPS for nondiagnostic
      ETT missed residual infarct-related artery stenosis and/or MVD in 31/81 (38%) of
      the cohort. Among patients who may not otherwise have been referred for
      angiography, severe (> or =70%) residual stenosis of the infarct-related artery
      was present in 56% and MVD in 16%. CONCLUSIONS: Early predischarge ETT and/or MPS
      had limited sensitivity for the detection of coronary disease in low-risk post
      STEMI patients. The study supports a simpler strategy of routine coronary
      angiography in most patients after low-risk STEMI.

PMID- 16567944
TI  - Epilepsy and obstructive sleep apnea.
AB  - A few publications documented the coexistence of epilepsy and obstructive sleep
      apnea (OSA). The extent, nature, and clinical relevance of this association
      remain poorly understood. We retrospectively reviewed the database of our sleep
      center to identify patients with both sleep apnea and epilepsy. Characteristics
      of epilepsy, sleep history, presence of excessive daytime sleepiness [Epworth
      Sleepiness Scale (ESS)] and polysomnographic data were assessed. The effect of
      continuous positive airway pressure (CPAP) on seizure reduction was prospectively
      analyzed after a median interval of 26 months (range: 2-116 months) from the
      diagnosis of OSA. OSA was found in 29 epilepsy patients (25 men and 4 women) with
      a median age of 56 years (range: 37-79). The median apnea hypopnea index was 33
      (range: 10-85), the oxygen desaturation index was 12 (range 0-92), and 52% of the
      patients had an ESS score >10. In 27 patients, epilepsy appeared 1 month to 44
      years prior to the diagnosis of OSA. In 21 patients, the appearance of OSA
      symptoms coincided with a clear increase in seizure frequency or the first
      appearance of a status epilepticus. Treatment with CPAP was continued with good
      compliance in 12 patients and led to a significant reduction of both ESS scores
      and seizure frequency in 4 patients. Our data suggest the importance of
      considering diagnosis and treatment of OSA in epilepsy patients with poor seizure
      control and/or reappearance of seizures after a seizure-free interval.

PMID- 16567945
TI  - Paraneoplastic rhombencephalitis and brachial plexopathy in two cases of
      amphiphysin auto-immunity.
AB  - Amphiphysin, a synaptic vesicle protein, is an auto-immune target in rare cases
      of paraneoplastic neurological disorders. We report two additional cases with
      distinct neurological syndromes and paraneoplastic anti-amphiphysin antibodies.
      The first patient, a 59-year-old man, presented with cerebellar and cranial nerve
      dysfunction and small cell lung carcinoma. The second, a 77-year- old woman,
      presented with left brachial plexopathy followed by sensorimotor neuropathy and
      breast carcinoma.

PMID- 16567946
TI  - Changes in gene expression during Wolffian duct development.
AB  - BACKGROUND: Wolffian ducts (WDs) are the embryonic precursors of the male
      reproductive tract. Their development is induced by testosterone, which interacts
      with the androgen receptor (AR). The molecular pathways underlying androgen
      dependent WD development are largely unknown. We aimed to identify AR target
      genes important in this process. METHODS: RNA was isolated from rat WDs at E17.5
      and E20.5. Affymetrix GeneChip expression arrays were used to identify
      transcripts up- or downregulated more than 2-fold. Regulation of seven
      transcripts was confirmed using quantitative PCR. RESULTS: Transcripts from 76
      known genes were regulated, including modulators of insulin-like growth factor
      and transforming growth factor-beta signalling. By controlling these modulators,
      androgens may indirectly affect growth factor signalling pathways important in
      epithelial-mesenchymal interactions and organ development. Caveolin-1, also
      upregulated, may play a role in modifying as well as mediating AR signalling.
      Differentiation of WD epithelium and smooth muscle, innervation and extracellular
      matrix synthesis were reflected in regulation of other transcripts. Several genes
      were previously suggested to be regulated by androgens or contained functional or
      putative androgen/glucocorticoid response elements, indicating they may be direct
      targets of androgen signalling. CONCLUSION: Our results suggest novel cohorts of
      signals that may contribute to androgen-dependent WD development and provide
      hypotheses that can be tested by future studies.

PMID- 16567947
TI  - Does the season or month of birth influence disease progression in multiple
      sclerosis?
AB  - We investigated the influence of season and birth month on sustained progression
      to Expanded Disability Status Scale 6 (requires a cane) through a database review
      of 2,319 definite multiple sclerosis (MS) patients followed for a mean 19.3
      years, until July 2003 in British Columbia, Canada. The season of birth had a
      marginal effect on disease progression (p = 0.051), with winter babies exhibiting
      the slowest progression (p = 0.048). Birth month had a significant effect on
      progression (p = 0.038), mainly due to those January born having a 40% (95% CI
      32.9-47.4) chance of requiring a cane later than those born in other months.
      There was some evidence to suggest that the gestational period had a small but
      long-lasting effect on later disease progression in British Columbia, Canada.

PMID- 16567948
TI  - Complications in children with long-term cochlear implants.
AB  - OBJECTIVES: To evaluate the complications in children who underwent cochlear
      implantation between 1991 and 2002 at Chi Mei Medical Center, Taipei Medical
      University. METHOD: The medical records of 169 cases of pediatric cochlear
      implants from 1991 to 2002 with a follow-up period of 3-11 years were reviewed
      for demographics and complications. A follow-up phone call and clinical visits
      were performed to determine the long-term results. RESULTS: The medical-surgical
      complications were facial nerve stimulation, transient dizziness, flap breakdown,
      minor change of taste, cholesteatoma, otitis media with effusion and mastoiditis.
      The device-related complications included 4 device failures and 1 device breakage
      in a traffic accident. CONCLUSION: Chronic otitis media and cholesteatoma
      developed in children as long-term complications and surgical challenges.
      Nevertheless, cochlear implantation surgery in children is a reliable and safe
      procedure with a low percentage of severe complications. To prevent cholesteatoma
      formation, parents are advised to schedule a regular ENT consultation at least
      yearly for early identification and treatment in the stages of acute otitis media
      or drum retraction.

PMID- 16567949
TI  - Should we use ossicular remnants in ossicular reconstruction following
      cholesteatoma removal?
AB  - The remnants of the acoustic ossicles have been used in ossicular reconstruction
      during mastoid surgery for many decades. The present study assessed the status of
      the acoustic ossicles in 114 patients (57 with cholesteatoma and 57 without)
      during surgery for chronic otitis media using the operating microscope. In 52
      cases, the ossicles (malleus and/or incus) were assessed using both the surgical
      and scanning electron microscope in order to reveal any erosions and compare the
      findings. From the 57 operated ears with cholesteatoma, 45 (79%) had ossicular
      erosion whereas 12 (21%) did not. In the group of 57 operated ears with chronic
      otitis media without cholesteatoma, 33 (58%) had ossicular erosion whereas 24
      (42%) did not. This difference was statistically significant (p = 0.02). With
      regard to the 52 operated cases who were studied with both microscopes, in the
      cholesteatoma patients the surgical microscope was not able to reveal any
      ossicular erosions in 39% of the cases, whereas the scanning electron microscope
      revealed moderate or severe erosions in the same ears. This suggests that the
      operating microscope is not reliable enough to determine if ossicular remnants
      can be used in ossicular reconstruction following cholesteatoma surgery. There is
      a considerable risk that epithelia or other cholesteatoma particles remain in the
      areas of erosions that cannot be seen with the operating microscope. The use of
      such ossicular remnants may lead to cholesteatoma recurrence and failures in
      mastoid surgery. Therefore, autoclaving or alternative prosthesis may be
      considered in such cases.

PMID- 16567952
TI  - New insights into carrier binding and epithelial uptake of the erythropoietic
      nutrients cobalamin and folate.
AB  - PURPOSE OF REVIEW: In addition to malnutrition several genetic and acquired
      conditions may affect the homeostasis of cobalamin (vitamin B12) and folate,
      leading to megaloblastic anemia and other diseases. The present review describes
      new insight into protein handling of cobalamin and folate. RECENT FINDINGS: The
      recent solution of the three-dimensional structure of the cobalamin binder
      transcobalamin shows two separate domains enclosing the vitamin. This structure
      apparently also applies for the other homologous cobalamin binders, intrinsic
      factor and haptocorrin. Genetic studies of inherited cobalamin malabsorption and
      biochemical studies have now revealed that the functional receptor for uptake of
      intrinsic factor-vitamin cobalamin complexes also is a complex itself consisting
      of two different gene products, cubilin and amnionless. A role in folate uptake
      of megalin, an endocytic receptor for epithelial uptake of various proteins
      including transcobalamin, is now also indicated by the observation that megalin
      can mediate uptake of soluble folate receptor. SUMMARY: New data show the
      structure of cobalamin carriers and reveal novel proteins involved in the
      epithelial uptake of cobalamin and folate. Genetic abnormalities in three
      different genes encoding proteins in the epithelial uptake of cobalamin are now
      known to cause malabsorption of cobalamin and megaloblastic anemia.

PMID- 16567950
TI  - Effect of atorvastatin treatment on isoproterenol-induced myocardial infarction
      in rats.
AB  - In the present study, chronic treatment of atorvastatin was evaluated on
      isoproterenol-induced myocardial infarction. Male Sprague-Dawley rats (200 +/- 25
      g) were randomized into the following four groups: (1) control group, (2)
      isoproterenol-treated group, (3) atorvastatin-treated group, and (4)
      isoproterenol- and atorvastatin-treated group. Various serum and tissue
      parameters as well as histopathological studies were carried out in all groups.
      Isoproterenol administration produced severe myocardial damage and oxidative
      stress in rats. Atorvastatin treatment reduced myocardial infarction which has
      been reflected by improvement in serum parameters, ATPase activities and
      histopathological lesions. However, it could not reduce oxidative stress and
      hypertrophy induced by isoproterenol. Hence, it can be concluded that
      atorvastatin may protect myocardial infarction induced by isoproterenol
      independent of its antioxidant properties.

PMID- 16567953
TI  - Modulation of malaria virulence by determinants of Plasmodium falciparum
      erythrocyte membrane protein-1 display.
AB  - PURPOSE OF REVIEW: Plasmodium falciparum malaria parasites carry approximately 60
      var genes that encode variable adhesins termed P. falciparum erythrocyte membrane
      protein-1. Clonal expression of a single P. falciparum erythrocyte membrane
      protein-1 variant on the surface of the parasitized host erythrocyte promotes
      binding of the cell to blood elements (including noninfected erythrocytes,
      leukocytes) and walls of microvessels. These binding events enable parasitized
      erythrocytes to sequester and avoid clearance by the spleen, and they also
      contribute to disease by causing microvascular inflammation and obstruction.
      RECENT FINDINGS: Steps by which P. falciparum erythrocyte membrane protein-1 is
      exported to the parasitized erythrocyte surface have recently been elucidated.
      The ability of parasites to cytoadhere and cause disease depends on the variant
      of P. falciparum erythrocyte membrane protein-1 as well as its amount and
      distribution at the erythrocyte surface. An example of a host polymorphism that
      affects P. falciparum erythrocyte membrane protein-1 display is hemoglobin C,
      which may protect against malaria by impairing the parasite's ability to adhere
      to microvessels and induce inflammation. Interference with P. falciparum
      erythrocyte membrane protein-1-mediated phenomena appears to diminish
      cytoadherence in vivo and to protect against disease in animal models. SUMMARY:
      Plasmodium falciparum erythrocyte membrane protein-1-mediated sequestration of
      parasitized erythrocytes plays a central role in malaria pathogenesis. Clinical
      interventions aimed at reducing cytoadherence and microvascular inflammation may
      improve disease outcome.

PMID- 16567954
TI  - Modifier genes and sickle cell anemia.
AB  - PURPOSE OF REVIEW: With the completion of the human genome project and HapMap,
      previously unknown genetic polymorphisms associated with disease have been
      observed. This review highlights genetic polymorphisms that have provided insight
      into the pathophysiology underlying the many phenotypes of sickle cell disease.
      RECENT FINDINGS: The phenotypes of sickle cell disease are likely to be modulated
      by polymorphisms in genes that are involved in inflammation, cell-cell
      interaction, and nitric oxide biology. Case-control studies are beginning to
      define the relationships between single-nucleotide polymorphisms in candidate
      genes and the many subphenotypes of sickle cell anemia. A common theme emerging
      from these studies is that single-nucleotide polymorphisms in genes of the
      transforming growth factor-beta/bone morphogenetic protein and a few other genes
      such as Klotho are associated with several subphenotypes of sickle cell disease.
      SUMMARY: Genomic medicine is merging with clinical practice as our understanding
      of the structure and variability of the human genome increases. Patients with
      diseases caused by identical mutations in a single gene - sickle cell anemia is a
      prime example - can have clinical courses very different from one another, and
      when environmental influences are removed the phenotypic heterogeneity of
      mendelian single-gene disorders is best explained by single-nucleotide
      polymorphisms in genes that modulate the disease phenotype. As this field
      expands, insights will be gained into complex epistatic factors that influence
      the clinical presentation of sickle cell disease, enabling physicians to better
      predict and manage the many complications of this disease.

PMID- 16567955
TI  - Erythroblastic islands: specialized microenvironmental niches for erythropoiesis.
AB  - PURPOSE OF REVIEW: This review focuses on current understanding of molecular
      mechanisms operating within erythroblastic islands including cell-cell adhesion,
      regulatory feedback, and central macrophage function. RECENT FINDINGS:
      Erythroblasts express a variety of adhesion molecules and recently two
      interactions have been identified that appear to be critical for island
      integrity. Erythroblast macrophage protein, expressed on erythroblasts and
      macrophages, mediates cell-cell attachments via homophilic binding. Erythroblast
      intercellular adhesion molecule-4 links erythroblasts to macrophages through
      interaction with macrophage alphav integrin. In intercellular adhesion molecule-4
      knockout mice, erythroblastic islands are markedly reduced, whereas the
      erythroblast macrophage protein null phenotype is severely anemic and embryonic
      lethal. Retinoblastoma tumor suppressor (Rb) protein stimulates macrophage
      differentiation by counteracting inhibition of Id2 on PU.1, a transcription
      factor that is a crucial regulator of macrophage differentiation. Rb-deficient
      macrophages do not bind Rb null erythroblasts and the Rb null phenotype is anemic
      and embryonic lethal. Lastly, extruded nuclei rapidly expose phosphatidylserine
      on their surface, providing a recognition signal similar to apoptotic cells.
      SUMMARY: Although understanding of molecular mechanisms operating within islands
      is at an early stage, tantalizing evidence suggests that erythroblastic islands
      are specialized niches where intercellular interactions in concert with cytokines
      play critical roles in regulating erythropoiesis.

PMID- 16567956
TI  - Recent advances in globin gene transfer for the treatment of beta-thalassemia and
      sickle cell anemia.
AB  - PURPOSE OF REVIEW: The beta-thalassemias and sickle cell anemia are severe
      congenital anemias for which there is presently no curative therapy other than
      allogeneic hematopoietic stem cell transplantation. This therapeutic option,
      however, is not available to most patients due to the lack of an HLA-matched bone
      marrow donor. The transfer of a regulated globin gene in autologous hematopoietic
      stem cells is therefore a highly attractive alternative treatment. This strategy,
      simple in principle, raises major challenges in terms of controlling transgene
      expression, which ideally should be erythroid specific, differentiation and stage
      restricted, elevated, position independent, and sustained over time. RECENT
      FINDINGS: Using lentiviral vectors, May et al. demonstrated that an optimized
      combination of proximal and distal transcriptional control elements permits
      lineage-specific and elevated beta-globin expression in vivo, resulting in
      therapeutic hemoglobin production and correction of anemia in beta-thalassemic
      mice. Several groups have extended these findings to various models of beta
      thalassemia and sickle cell disease. While the addition of the wild-type beta
      globin gene is naturally suited for treating beta-thalassemia, several
      alternatives have been proposed for the treatment of sickle cell disease, using
      either gamma or mutant beta-globin gene addition, trans-splicing or RNA
      interference. SUMMARY: These recent advances bode well for the clinical
      investigation of stem cell-based gene therapy in the severe hemoglobinopathies.

PMID- 16567958
TI  - Transcriptional regulation of megakaryopoiesis: thrombopoietin signaling and
      nuclear factors.
AB  - PURPOSE OF REVIEW: Thrombopoietin, the primary regulator of megakaryopoiesis,
      acts by modulating several nuclear transcription factors. This review focuses on
      recent studies that have provided new insights into the functional roles of these
      proteins. RECENT FINDINGS: Among the transcription factors responsible for
      megakaryopoiesis, important roles for the signal transducer and activator of
      transcription and Forkhead box proteins have been defined. In addition, in the
      past several years, two new groups of transcription factors have been found to be
      affected by thrombopoietin signaling, homeodomain-containing HOX proteins and
      hypoxia-inducible factor. The HOX transcription factors, which play key roles in
      body pattern development, are also expressed in adult hematopoietic stem cells
      and play pivotal roles in their proliferation. Thrombopoietin controls the levels
      of expression and modifies the function of homeodomain proteins in thrombopoietin
      responsive leukemic cells and in primary immature hematopoietic cells. Levels of
      hypoxia-inducible factor, a master transcription factor required for the
      adaptation to hypoxic conditions, is also affected by thrombopoietin in these
      cells. SUMMARY: The discovery that a diverse range of transcription factors are
      downstream effectors of thrombopoietin helps to explain the molecular mechanisms
      by which the hormone affects hematopoiesis.

PMID- 16567959
TI  - Inherited disorders of platelets: an update.
AB  - PURPOSE OF REVIEW: To overview inherited syndromes that affect platelets and to
      discuss current data on the molecular origin and management of these rare
      diseases. RECENT FINDINGS: An increasing number of genes responsible for
      inherited thrombocytopenias have been identified and these now extend to
      glycosylation defects. Although Glanzmann thrombasthenia remains the predominant
      disorder of platelet function, knowledge is increasing of pathologies concerning
      primary receptors for adhesion and signalling, the activation and secretory
      pathways, and even the development of procoagulant activity. SUMMARY: These
      syndromes affect cell adhesion, cell activation, and cell-to-cell contact
      interactions fundamental in cell biology. Studies on the pathophysiology of
      alphaIIbbeta3 in platelets have helped unravel the molecular mechanisms of
      integrin function, and the information gained has resulted in improved
      antithrombotic therapy. The establishment of national registries and the use of
      state-of-the-art genomic and proteomic technologies will accelerate progress and
      help to define how mutations affecting a much larger range of proteins contribute
      alone or in combination to defining specific platelet phenotypes.

PMID- 16567960
TI  - Toll-like receptor signaling and atherosclerosis.
AB  - PURPOSE OF REVIEW: Chronic inflammation and disordered lipid metabolism represent
      hallmarks of atherosclerosis. Considerable evidence has accumulated to suggest
      that innate immune defense mechanisms might interact with proinflammatory
      pathways and exacerbate or perhaps even initiate development of arterial plaques.
      Until recently the preponderance of such evidence has been indirectly emerging
      from clinical and epidemiologic studies, with some support from experimental
      animal models of atherosclerosis. RECENT FINDINGS: Recent data now directly
      implicate signaling by toll-like receptor 4 and the common adaptor molecule MyD88
      in the pathogenesis of atherosclerosis, establishing a key link between
      atherosclerosis and defense against both foreign pathogens and endogenously
      generated inflammatory ligands. SUMMARY: Here we briefly review these and closely
      related studies, highlighting areas that should provide fertile ground for future
      studies aimed at a more comprehensive understanding of the interplay between
      innate immune defense mechanisms, atherosclerosis and related vascular disorders.

PMID- 16567961
TI  - Hypoxia-inducible factors, hypoxia, and tumor angiogenesis.
AB  - PURPOSE OF REVIEW: The transcription factor hypoxia-inducible factor is activated
      by low oxygen to promote the expression of target genes that allow cellular,
      tissue, and organismal adaptation to low oxygen. Hypoxia-inducible factor is
      activated not only by hypoxia but also as a consequence of genetic mutations in a
      variety of tumors. This review summarizes recent studies on hypoxia-inducible
      factor-alpha functions in development and tumorigenesis. RECENT FINDINGS:
      Deficiency of the tumor suppressor von Hippel-Lindau leads to constitutively
      active hypoxia-inducible factor and hypoxia-inducible factor target gene
      expression. Other genetic lesions, however, e.g. in JunD, can also result in
      elevated hypoxia-inducible factor levels. The specific functions of hypoxia
      inducible factor-1alpha and hypoxia-inducible factor-2alpha during development
      and tumor growth remain incompletely understood. Whereas hypoxia-inducible factor
      2alpha seems to be the critical hypoxia factor in renal cell carcinoma, hypoxia
      inducible factor-1alpha plays a significant role in the growth of tumors in other
      tissues. Loss of von Hippel-Lindau is not sufficient for neoplastic
      transformation, suggesting that hypoxia-inducible factor does not act alone to
      cause tumors. SUMMARY: It will be important to further characterize the specific
      roles of hypoxia-inducible factor-1alpha and hypoxia-inducible factor-2alpha
      during tumorigenesis to design therapies targeting the relevant isoform for
      specific diseases. It is also necessary to investigate the effect of reducing
      hypoxia-inducible factor levels on other angiogenic factors.

PMID- 16567963
TI  - Bibliography. Current world literature. Erythroid system and its diseases.

PMID- 16567964
TI  - BRAF somatic mutations in malignant melanoma and melanocytic naevi.
AB  - BRAF somatic mutations are frequently found in primary and metastatic melanomas
      and melanocytic naevi. Commonly found BRAF mutants stimulate constitutive RAF/MEK
      (mitogen-activated ERK-activating kinase)/ERK (extracellular signal-regulated
      kinase) pathway activation and act as transforming oncogenes in NIH-3T3 cells and
      immortalized murine melanocytes. The most common BRAF mutation is the V600E
      alteration, but over 30 distinct BRAF mutations, varying in biological activity,
      have been found and may be predictive of clinically relevant tumour differences.
      The origin of these acquired mutations remains unknown, but melanomas have a
      different BRAF mutational spectrum from other tumours, possibly resulting from
      unique environmental exposures. In melanoma cases, BRAF mutations are frequently
      found in superficial spreading or nodular histological subtypes, in tumours on
      intermittently sun-exposed sites and in younger patients. Although evidence
      indicates that the activation of the RAF/MEK/ERK pathway influences the
      proliferation, invasion and survival of melanoma cells in vitro, the exact role
      of BRAF mutation in melanoma tumour progression, maintenance and outcome remains
      controversial. In addition, although BRAF and NRAS mutations are mutually
      exclusive in melanomas, other genetic events may complement BRAF mutation to
      produce biological activity similar to NRAS mutation. Nonetheless, preclinical
      and early clinical studies predict that RAF/MEK/ERK pathway inhibitors will have
      therapeutic activity towards melanoma, but that tumour subclassification by
      BRAF/NRAS mutational status may be necessary to evaluate their efficacy.

PMID- 16567962
TI  - Contribution of endothelial progenitors and proangiogenic hematopoietic cells to
      vascularization of tumor and ischemic tissue.
AB  - PURPOSE OF REVIEW: During the last several years, a substantial amount of
      evidence from animal as well as human studies has advanced our knowledge of how
      bone marrow derived cells contribute to neoangiogenesis. In the light of recent
      findings, we may have to redefine our thinking of endothelial cells as well as of
      perivascular mural cells. RECENT FINDINGS: Inflammatory hematopoietic cells, such
      as macrophages, have been shown to promote neoangiogenesis during tumor growth
      and wound healing. Dendritic cells, B lymphocytes, monocytes, and other immune
      cells have also been found to be recruited to neoangiogenic niches and to support
      neovessel formation. These findings have led to the concept that subsets of
      hematopoietic cells comprise proangiogenic cells that drive adult
      revascularization processes. While evidence of the importance of endothelial
      progenitor cells in adult vasculogenesis increased further, the role of these
      comobilized hematopoietic cells has been intensely studied in the last few years.
      SUMMARY: Angiogenic factors promote mobilization of vascular endothelial growth
      factor receptor 1-positive hematopoietic cells through matrix metalloproteinase-9
      mediated release of soluble kit-ligand and recruit these proangiogenic cells to
      areas of hypoxia, where perivascular mural cells present stromal-derived factor 1
      (CXCL-12) as an important retention signal. The same factors are possibly
      involved in mobilization of vascular endothelial growth factor receptor 2
      positive endothelial precursors that may participate in neovessel formation. The
      complete characterization of mechanisms, mediators and signaling pathways
      involved in these processes will provide novel targets for both anti and
      proangiogenic therapeutic strategies.

PMID- 16567965
TI  - Genomic stability in malignant melanoma of Xiphophorus.
AB  - Microsatellite instability is a feature of many tumours and is indicative of a
      generalized genomic instability of cancer cells. Whether this phenomenon is
      essential for tumorigenesis and whether it is an early or late step is still a
      matter of debate. In the Xiphophorus melanoma model, the primary steps leading to
      tumour formation are known and include overexpression of a mutationally altered
      epidermal growth factor receptor and the resulting defects in signalling. We have
      analysed the late stages of melanoma progression for microsatellite instability.
      Although several types of microsatellite allele alteration in DNA from tumours
      relative to DNA from non-tumour tissue were found, the frequency was rather low
      (7.6%). Thus, although the tumours show a wide range of malignancy and
      aggressiveness, genomic instability that becomes apparent as microsatellite
      instability does not appear to be an obligatory step for melanoma progression.

PMID- 16567966
TI  - A theory and model to explain the skin melanoma epidemic.
AB  - Before 1955, the incidence of malignant melanoma in Nordic countries increased
      from birth to approximately 30 years of age, when it levelled off to around five
      cases per 100,000 person-years. From 1957 onwards, the incidence no longer
      stabilized at the age of 30 years, but continued to increase with age to at least
      100 cases per 100,000 person-years. The aims of this study were to examine this
      sudden change in melanoma trends and to develop an explanatory model. The Nordic
      Cancer Registries and the American Cancer Society provided age-specific incidence
      data. Birth cohorts of melanoma incidence for men were plotted against calendar
      year and age. A theory and a corresponding mathematical model were developed to
      explain the time trends in all cohorts, as well as the reported age-specific
      incidence and age-standardized incidence over time. A statistical distribution of
      time to sickness fitted all the post-1957 data. Earlier studies have indicated
      that body-resonant frequency modulation broadcasting radiation from 1955 onwards
      may affect melanoma incidence. The proposed model may shed light on the melanoma
      epidemic and may be useful in predicting future melanoma trends based on known
      birth cohort data and possible effects from policy changes with regard to
      population exposure to electromagnetic radiation.

PMID- 16567967
TI  - Influence of angiogenin on the growth of A375 human melanoma cells and the
      expression of basic fibroblast growth factor.
AB  - Angiogenin was isolated as a tumor angiogenic factor solely on the basis of its
      angiogenic activity. Its expression is essential for melanoma progression and
      metastasis. Many studies have mainly focused on how it induces angiogenesis,
      which allows further melanoma growth and metastasis. Here, we investigated the
      effects of angiogenin on melanoma cell growth and studied its influence on the
      expression and function of the basic fibroblast growth factor. We transfected the
      angiogenin gene in the sense and antisense orientation into A375 cells, and
      obtained stable angiogenin under-expressing and over-expressing transfectants. We
      found that in the angiogenin antisense transfectants, the cell proliferation was
      decreased and the basic fibroblast growth factor-induced cell proliferation was
      inhibited, but the expression of basic fibroblast growth factor was increased. In
      contrast, in the angiogenin sense transfectants, the cell proliferation was
      increased, and the basic fibroblast growth factor-induced cell proliferation was
      also increased. The expression of basic fibroblast growth factor, however, was
      decreased. In conclusion, we demonstrated that, besides its angiogenic activity,
      angiogenin also directly contributes to A375 cell proliferation and is required
      for the basic fibroblast growth factor to induce cell proliferation. We also
      demonstrated that the endogenous angiogenin expression levels affect the
      expression of basic fibroblast growth factor in A375 cells. By targeting
      angiogenin, therefore, one may find a potential therapeutic approach to human
      malignant melanoma.

PMID- 16567968
TI  - Antiproliferative effect of STI571 on cultured human cutaneous melanoma-derived
      cell lines.
AB  - Standard antineoplastic treatment for metastatic melanoma is ineffective in the
      large majority of patients. Therefore, alternative approaches need to be
      investigated. STI571 is a new antineoplastic compound, which selectively inhibits
      the tyrosine kinase activity of ABL, c-Kit and platelet-derived growth factor
      receptor (PDGFR). Melanoma may express all of these proteins. The aim of this
      study was to investigate whether STI571 inhibits the in-vitro growth of melanoma
      cells. Nineteen cell lines were obtained from four primary and 15 metastatic
      melanomas of cutaneous origin. The percentages of positive cells for the putative
      targets of STI571 were as follows: ABL, 41-100%; c-Kit, 8-97%; PDGFR-alpha, 41
      98%; PDGFR-beta, 51-99%. 3-(4,5-Dimethylthiazol-yl)-2,5-diphenyltetrazolium (MTT)
      and viability assays showed that STI571 clearly inhibits the proliferation of
      eight of the 19 (42.1%) cell lines. No relationship could be established between
      the expression of c-Kit, ABL, PDGFR-alpha or PDGFR-beta and the response of cell
      lines to STI571. Our study shows, for the first time, an antiproliferative effect
      of STI571 on human melanoma cell lines of cutaneous origin, raising the
      possibility of the future clinical use of STI571. The identification of the
      target of STI571 in human cutaneous melanoma cells would allow the selection of
      patients who could benefit from this treatment.

PMID- 16567969
TI  - Concordant loss of melanoma differentiation antigens in synchronous and
      asynchronous melanoma metastases: implications for immunotherapy.
AB  - Because of its known heterogeneity, the analysis of antigen expression is crucial
      prior to the initiation of antigen-specific immunotherapy for melanoma. The
      melanoma differentiation antigens gp100, MART-1 and tyrosinase are involved in a
      common pathway of melanin synthesis. Peptides derived from these melanoma
      differentiation antigens are used in the immunotherapy of melanoma and antibodies
      recognizing these antigens are commonly applied to detect melanocytic lesions.
      One hundred and ninety-one paraffin-embedded melanoma metastases from 28 patients
      with 2-19 lesions (mean, 6.8) developing synchronously (n = 67) or asynchronously
      (n = 124) were analysed by immunohistochemistry for the expression of the
      melanoma differentiation antigens, as well as cancer/testis antigens of the
      melanoma antigen-A (MAGE-A) family (monoclonal antibodies 77B and 57B), anti-S100
      and SM5-1. The overall reactivities were 81.6% (gp100), 79.5% (MART-1), 59.6%
      (tyrosinase), 59.1% (77B), 60.7% (57B), 93.2% (S100) and 91.6% (SM5-1). Twenty
      seven lesions (14.1%) were positive for all tumour-associated antigens, 75
      lesions (39.2%) were negative for one antigen and 87 lesions (45.5%) were
      negative for several tumour-associated antigens. Co-ordinated loss was found for
      lesions negative for gp100 and MART-1 (9.4%, P < 0.0005), gp100 and tyrosinase
      (11.0%, P = 0.009), MART-1 and tyrosinase (15.2%, P < 0.0005) and gp100, MART-1
      and tyrosinase (8.9%, P < 0.0005), which is up to six times higher than the
      expected calculated loss. This co-ordinated loss of melanoma differentiation
      antigens in melanoma did not include cancer testis antigens and S100 or SM5-1. On
      average, the melanoma differentiation antigens stained 50-65% of cells within a
      lesion, and 10-39% of synchronous clusters were heterogeneous for melanoma
      differentiation antigen expression. In conclusion, broader polypeptide vaccines
      should be used for melanoma immunotherapy.

PMID- 16567970
TI  - Analysis of gene expression profiles in melanoma cells with acquired resistance
      against antineoplastic drugs.
AB  - Resistance to various antineoplastic agents is common in the clinical management
      of malignant melanoma. The biological mechanisms conferring these different drug
      resistant phenotypes are still unclear. To identify potential factors mediating
      drug resistance to melanoma cells, the mRNA expression profiles of the parental
      drug-sensitive human melanoma cell line MeWo and four derived drug-resistant
      sublines with acquired resistance against four commonly used drugs for melanoma
      treatment (cisplatin, etoposide, fotemustine and vindesine) were analysed. We
      investigated cDNA arrays with 43,000 cDNA clones ( approximately 30,000 unique
      genes) to study the expression patterns of these cell lines. We were able to
      simultaneously extract new candidate genes associated with drug resistance in
      malignant melanoma and to correlate the present findings with previously
      described resistance-associated genes. Using hierarchical clustering and
      analysing the overlap of genes with altered expression, we detected similarities
      between the expression signatures related to cisplatin and fotemustine
      resistance. The resistance against vindesine required a minimal set of changes in
      gene expression relative to the parental MeWo cell line. Our study provides new
      data that may be used to obtain further insight into the resistance
      characteristics of malignant melanoma.

PMID- 16567971
TI  - Anti-alphaGal-dependent complement-mediated cytotoxicity in metastatic melanoma.
AB  - Antibodies to the cell surface disaccharide galactose(alpha1,3)galactose
      (alphaGal) are the most prevalent natural antibodies in human serum. The anti
      alphaGal immunoglobulin M-dependent activation of complement causes hyperacute
      rejection of organ transplants from discordant species by human recipients. It
      has been shown in vitro that human tumour cells transduced with the gene that
      synthesizes alphaGal become sensitive to human serum. A prerequisite for anti
      alphaGal antibody-based therapeutic strategies is that patients with cancer have
      adequate serum levels of anti-alphaGal immunoglobulins and complement. The
      objective of this work was to measure the levels and function of anti-alphaGal
      immunoglobulins and complement in the serum of patients with metastatic melanoma
      and healthy volunteers. Serum complement levels were assayed by radial
      immunodiffusion. Anti-alphaGal immunoglobulin G and immunoglobulin M titres were
      measured by enzyme-linked immunosorbent assay. Disaccharide sugar blocking was
      used to investigate antibody specificity. The functional integrity of anti
      alphaGal antibodies and complement was investigated in cell lysis assays. It was
      found that the levels of the complement components C1q, C3 and C4 and the
      function of the classical complement pathway were normal in metastatic melanoma
      patients. Anti-alphaGal antibody titres were as variable in metastatic melanoma
      patients as in healthy controls, and the lysis of alphaGal-expressing cells
      correlated with anti-alphaGal immunoglobulin M titre (P < 0.0001). Anti-alphaGal
      antibody titres, complement levels and overall cytolytic function in the serum of
      patients with metastatic melanoma were indistinguishable from those of healthy
      controls. There is thus nothing intrinsic to the disease that will limit anti
      alphaGal-based therapeutic strategies for enhanced antigen presentation or
      induced cell lysis, including the mimicry of hyperacute rejection.

PMID- 16567972
TI  - Accumulation of low-avidity anti-melanocortin receptor 1 (anti-MC1R) CD8+ T cells
      in the lesional skin of a patient with melanoma-related depigmentation.
AB  - Spontaneous or therapy-induced depigmentation in patients with melanoma has long
      been considered a favourable prognostic indicator. In this report, we isolated T
      cells infiltrating the depigmented skin of an HLA-A2+/DR4+ patient with melanoma,
      and detected a very high frequency of CD8+ T cells specific for melanocortin
      receptor 1 (MC1R), a hormone receptor involved in cutaneous pigmentation. In
      particular, tissue-infiltrating CD8+ T cells dominantly recognized the novel
      MC1R52-60 peptide epitope in an HLA-A2-restricted manner, and peptide-reactive
      CD8+ T cells were also detected in freshly isolated peripheral blood from this
      patient. Although type 1 CD4+ T-cell responses against MC1R were not detected in
      fresh tissue isolates, short-term in-vitro stimulation of peripheral blood
      lymphocytes resulted in the rapid expansion of CD4+ T cells reactive against
      novel HLA-DR4-presented epitopes derived from the MC1R protein (i.e. MC1R82-95,
      MC1R105-118 and MC1R149-161). MC1R peptide-specific CD8+ T-cell clones isolated
      from the depigmented skin of this patient were characterized by comparatively low
      functional avidity for specific major histocompatibility complex-peptide
      complexes and were poorly lytic; however, these effector cells were capable of
      secreting both interferon-gamma and granzyme B against relevant target cells in
      vitro, and may have played an important role in the induction of leucoderma in
      situ in this patient.

PMID- 16567973
TI  - Contribution of melanocortin-1 receptor gene variants to sporadic cutaneous
      melanoma risk in a population in central Italy: a case-control study.
AB  - The melanocortin-1 receptor (MC1R) gene is a key determinant of the physiological
      variation in human skin pigmentation. It is highly polymorphic, and specific MC1R
      allelic variants have been shown to be low-penetrance melanoma susceptibility
      alleles. We investigated the contribution of the MC1R genotype to the risk of
      sporadic cutaneous melanoma in a population in central Italy. One hundred
      patients with sporadic cutaneous melanoma of any stage and 100 unrelated control
      individuals were consecutively recruited between 1 September 2000 and 31 December
      2001. Information on ethnic background and residential history, phenotypic risk
      factors for melanoma and ultraviolet exposure habits was collected through a
      standardized questionnaire and total skin examination. Sequence analysis of the
      entire coding region of the MC1R gene was performed. A total of 26 MC1R variants,
      including a novel 123_124insT allele, was identified in our population, with the
      most frequent allele being V60L. Carriers of high-penetrance 'R' MC1R alleles,
      that define MC1R variants strongly associated with the red hair colour phenotype,
      showed a statistically significant increase in melanoma risk [odds ratio (OR),
      2.55; 95% confidence interval (CI), 1.19-5.55]. No significant association with
      melanoma risk was observed for carriers of 'r' variants (OR, 0.90; 95% CI, 0.45
      1.82). Amongst individual MC1R variants, the R151C allele was significantly
      associated with melanoma, with an OR of 2.94 (95% CI, 1.04-8.31). After
      stratification for clinical and ultraviolet exposure risk factors, the melanoma
      risk associated with high-penetrance 'R' variants appeared to increase
      significantly, mainly in the presence of clinically atypical naevi, more than 50
      melanocytic naevi, high recreational sun exposure and occupational sun exposure.
      These results support the contribution of high-penetrance MC1R variant alleles to
      genetic predisposition to sporadic cutaneous melanoma in a population in central
      Italy.

PMID- 16567974
TI  - Quantitative assessment of tumour extraction from dermoscopy images and
      evaluation of computer-based extraction methods for an automatic melanoma
      diagnostic system.
AB  - The aims of this study were to provide a quantitative assessment of the tumour
      area extracted by dermatologists and to evaluate computer-based methods from
      dermoscopy images for refining a computer-based melanoma diagnostic system.
      Dermoscopic images of 188 Clark naevi, 56 Reed naevi and 75 melanomas were
      examined. Five dermatologists manually drew the border of each lesion with a
      tablet computer. The inter-observer variability was evaluated and the standard
      tumour area (STA) for each dermoscopy image was defined. Manual extractions by 10
      non-medical individuals and by two computer-based methods were evaluated with STA
      based assessment criteria: precision and recall. Our new computer-based method
      introduced the region-growing approach in order to yield results close to those
      obtained by dermatologists. The effectiveness of our extraction method with
      regard to diagnostic accuracy was evaluated. Two linear classifiers were built
      using the results of conventional and new computer-based tumour area extraction
      methods. The final diagnostic accuracy was evaluated by drawing the receiver
      operating curve (ROC) of each classifier, and the area under each ROC was
      evaluated. The standard deviations of the tumour area extracted by five
      dermatologists and 10 non-medical individuals were 8.9% and 10.7%, respectively.
      After assessment of the extraction results by dermatologists, the STA was defined
      as the area that was selected by more than two dermatologists. Dermatologists
      selected the melanoma area with statistically smaller divergence than that of
      Clark naevus or Reed naevus (P = 0.05). By contrast, non-medical individuals did
      not show this difference. Our new computer-based extraction algorithm showed
      superior performance (precision, 94.1%; recall, 95.3%) to the conventional
      thresholding method (precision, 99.5%; recall, 87.6%). These results indicate
      that our new algorithm extracted a tumour area close to that obtained by
      dermatologists and, in particular, the border part of the tumour was adequately
      extracted. With this refinement, the area under the ROC increased from 0.795 to
      0.875 and the diagnostic accuracy showed an increase of approximately 20% in
      specificity when the sensitivity was 80%. It can be concluded that our computer
      based tumour extraction algorithm extracted almost the same area as that obtained
      by dermatologists and provided improved computer-based diagnostic accuracy.

PMID- 16567975
TI  - Familial risks for eye melanoma and retinoblastoma: results from the Swedish
      Family-Cancer Database.
AB  - No systematic population-based studies have been conducted on familial eye
      cancers. Reliable data on familial risks are important for clinical counselling
      and cancer genetics. The current analysis was based on the nation-wide Swedish
      Family-Cancer Database on 10.5 million individuals, containing families with
      parents and offspring. Cancer data were retrieved from the Swedish Cancer
      Registry from the years 1958 to 2002, including 3636 patients with any type of
      eye cancer. Familial risk for offspring was defined using the standardized
      incidence ratio (SIR), adjusted for many variables. Ocular melanoma was detected
      in two parent-offspring pairs, but the SIR of 3.90 was not significant. Parental
      upper aerodigestive tract (2.05), left-sided colon (1.83) and male non-medullary
      thyroid (6.98) cancers showed an association with ocular melanoma, albeit some
      with a borderline significance. The SIR for leukaemia was increased when parents
      were diagnosed with eye melanoma. There was no evidence for the association of
      ocular melanoma with cutaneous melanoma. The SIR for ocular melanoma was 1.76
      when a sister was diagnosed with breast cancer, but there was no increase when a
      mother was diagnosed with breast cancer. When both a child and the parent
      presented with retinoblastoma, the SIR was 900. The parents of children with
      retinoblastoma had an excess of small intestinal and rectal cancers and Hodgkin's
      disease. The present findings were based on a limited number of cases, but they
      display a complex and heterogeneous pattern of familial associations in ocular
      melanoma, including an association with breast cancer through a putative
      recessive mechanism.

PMID- 16567976
TI  - Mutations of PIK3CA are rare in cutaneous melanoma.
AB  - Recent studies have shown that the PIK3CA gene, which encodes the p110alpha
      catalytic subunit of phosphatidylinositol 3-kinases, is mutated in human cancers.
      To determine whether PIK3CA is altered in cutaneous melanoma, we screened a
      series of 101 melanoma metastases. We identified PIK3CA missense mutations in
      three metastases (3%). Interestingly, these mutations were observed only in
      tumours that were negative for NRAS mutations. Using immunohistochemistry, we
      also analysed our metastases for the expression of phosphorylated Akt. These
      analyses revealed a moderate to strong phosphorylated Akt expression in 78% (21
      of 27) of metastases with NRAS mutations and in 73% (54 of 74) of metastases
      without NRAS mutations. Interestingly, the three metastases with mutations in
      PIK3CA all exhibited a strong expression of phosphorylated Akt. Taken together,
      our results show that PIK3CA is mutated in a minority of melanomas and suggest
      that mutations in this gene may represent an alternative mechanism of Akt
      activation in cutaneous melanoma.

PMID- 16567978
TI  - Safety and immunogenicity of a measles, mumps, rubella and varicella vaccine
      given with combined Haemophilus influenzae type b conjugate/hepatitis B vaccines
      and combined diphtheria-tetanus-acellular pertussis vaccines.
AB  - BACKGROUND: A study was conducted to assess administration of a combination
      measles, mumps, rubella and varicella vaccine (MMRV) with other childhood
      vaccines. METHODS: In this open, multicenter trial, 1915 healthy children ages 12
      15 months were randomized into 3 groups: group 1, MMRV, combined Haemophilus
      influenzae type b conjugate-hepatitis B vaccines (Hib/HepB) and combined
      diphtheria-tetanus-acellular pertussis vaccines (DTaP) concomitantly; group 2,
      MMRV followed by Hib/HepB and DTaP 42 days later; group 3, MMR and varicella
      vaccine followed by Hib/HepB and DTaP 42 days later. RESULTS: Antibody responses
      to measles, mumps, rubella, varicella, Hib, HepB, diphtheria and tetanus were
      similar between groups 1 and 2 (all >95%, except varicella, 89.7% in group 1 and
      90.9% in group 2). Pertussis toxin and filamentous hemagglutinin responses were
      significantly lower in group 1 than in group 2 (group 1, 74.1 and 67.1%; group 2,
      90.4 and 86.8%, respectively). An exploratory analysis suggested that the
      difference in and pertussis toxin and filamentous hemagglutinin responses was
      likely the result of study design rather than interference among vaccine
      components because the groups differed in age of receipt of DTaP (group 1,
      approximately 12 months; group 2, approximately 13.5 months). When the groups
      were matched for age, sample size was sufficient for comparison only in children
      > or =13.5 months old. Pertussis toxin and filamentous hemagglutinin responses
      were similar in these children. The safety profiles for each vaccination regimen
      were comparable. CONCLUSIONS: The immunogenicity data support concomitant
      administration of MMRV with Hib/HepB. Limited data from an exploratory analysis
      indicate that MMRV can be administered concomitantly with DTaP. Concomitant
      administration of MMRV, Hib/HepB and DTaP is well-tolerated.

PMID- 16567979
TI  - Changing epidemiology of outpatient bacteremia in 3- to 36-month-old children
      after the introduction of the heptavalent-conjugated pneumococcal vaccine.
AB  - BACKGROUND: The introduction of routine vaccination with heptavalent conjugated
      pneumococcal vaccine has changed the overall incidence of bacteremia in children
      3 months-3 years old. OBJECTIVE: To describe the changing incidence and etiology
      of bacteremia in previously healthy toddlers presenting to outpatient clinical
      settings. METHODS: Retrospective case series of all blood cultures obtained
      between September 1998 and August 2003 in Kaiser Permanente Northern California
      outpatient clinics and emergency departments from previously healthy children 3
      months-3 years old. RESULTS: Implementation of routine vaccination with the
      conjugated pneumococcal vaccine resulted in an 84% reduction of Streptococcus
      pneumoniae bacteremia (1.3-0.2%) and a 67% reduction in overall bacteremia (1.6
      0.7%) in the study population. The rate of blood culture isolation of
      contaminating organisms remained unchanged at 1.8%; therefore, by the end of the
      study, >70% of organisms identified in blood cultures were contaminants. During
      the 5 study years, total blood cultures drawn decreased by 35% in outpatient
      pediatric clinics but remained unchanged in emergency departments. By 2003, one
      third of all pathogenic organisms isolated from blood cultures were Escherichia
      coli, one-third were non-vaccine serotype S. pneumoniae, the majority of the
      remaining one-third were Staphylococcus aureus, Salmonella spp., Neisseria
      meningitidis and Streptococcus pyogenes. In our population of children routinely
      immunized with the conjugated pneumococcal vaccine, a white blood cell count
      >15,000 by itself is a poor predictor of bacteremia in the febrile toddler
      (sensitivity, 74.0%; specificity, 54.5%; positive predictive value, 1.5%;
      negative predictive value, 99.5%). CONCLUSION: In the United States, routine
      vaccinations with Haemophilus influenzae type b and S. pneumoniae vaccines have
      made bacteremia in the previously healthy toddler a rare event. As the incidence
      of pneumococcal bacteremia has decreased, E. coli, Salmonella spp. and
      Staphylococcus aureus have increased in relative importance. The use of the white
      blood cell count alone to guide the empiric use of antibiotics is not indicated.
      New guidelines are needed to approach the previously healthy febrile toddler in
      the outpatient setting.

PMID- 16567980
TI  - Streptococcus pneumoniae serogroups 15 and 33: an increasing cause of
      pneumococcal infections in children in the United States after the introduction
      of the pneumococcal 7-valent conjugate vaccine.
AB  - BACKGROUND: After the widespread use of the 7-valent pneumococcal conjugate
      vaccine, replacement serotypes have emerged. Serogroups 15 and 33 have emerged as
      nonvaccine serotypes causing invasive disease. We describe the clinical
      characteristics of children with infections caused by these serogroups and
      determined the genetic relationship of the strains. MATERIALS AND METHODS: The
      United States Pediatric Multicenter Pneumococcal Surveillance Group has
      prospectively identified children with pneumococcal infections since 1993. Charts
      were reviewed retrospectively, isolates were serogrouped and serotyped and
      randomly selected strains were fingerprinted with the use of pulsed field gel
      electrophoresis. Selected strains were further characterized by multilocus
      sequence typing. RESULTS: Between January 1994 and December 2004, 103 children
      had pneumococcal disease caused by serogroup 15, and 40 children had infections
      caused by serogroup 33. There was an increase from a mean of 7 cases per year for
      serogroup 15 in the prevaccine period to 14 cases per year in the postvaccine
      period and from 2 cases per year for serogroup 33 to 7 cases per year in the same
      periods. Isolates were susceptible to penicillin and ceftriaxone in both periods.
      A predominant clone was found in each serogroup representing 60% (30 of 50) of
      serogroup 15 strains and 83% (24 of 29) of the serotype 33F strains. The
      serogroup 15 clone comprised strains of serotypes 15B and 15C, whereas the 33
      clone contained only serotype 33F strains. One isolate from each of the 15 and 33
      clones was characterized by multilocus sequence typing and were found to be ST199
      and 100, respectively. CONCLUSIONS: Pneumococcal disease in children caused by
      penicillin-susceptible clones of serogroups 15 and 33 is increasing in the United
      States. Clinicians should consider replacement serotypes when encountered with
      invasive pneumococcal disease in vaccinated children.

PMID- 16567981
TI  - Immunogenicity and safety of measles-mumps-rubella, varicella and Haemophilus
      influenzae type b vaccines administered concurrently with a fourth dose of
      heptavalent pneumococcal conjugate vaccine compared with the vaccines
      administered without heptavalent pneumococcal conjugate vaccine.
AB  - BACKGROUND: Prevnar [heptavalent pneumococcal conjugate vaccine (PCV7)] is
      licensed in the United States for routine administration in infants and may be
      coadministered with other infant vaccines. Safety and immunogenicity data on the
      coadministration of the fourth dose of PCV7 with measles-mumps-rubella (MMR),
      varicella and Haemophilus influenzae type b (Hib) vaccines are limited. METHODS:
      Children 12-15 months of age received either MMR with PCV7 (group 1) or MMR
      without PCV7 (group 2). All subjects received Hib and varicella vaccines. Group 2
      received PCV7 6-9 weeks after MMR vaccination. Sera for analysis of all non-PCV7
      antibodies were collected just before administration of MMR vaccine and 6 weeks
      later. Optimal antigen responses were assessed with the use of predetermined
      antibody titers. The primary end point was >90% response rate (all antigens).
      Noninferiority was defined as <10% difference between groups. Local and systemic
      reactions and postvaccination adverse events were monitored and compared between
      groups. RESULTS: A total of 694 subjects (347 per group) were enrolled. After
      immunization with MMR plus PCV7 concurrently, or MMR followed 6 weeks later by
      PCV7, the percentages of subjects seroconverting were significantly greater than
      90% for all antigens. The difference between the 2 groups was significantly less
      than 10%. CONCLUSION: The immune response to MMR, Hib and varicella vaccines,
      when administered concurrently with a 4th (booster) dose of PCV7, was noninferior
      to that of these vaccines when given without PCV7. These results support
      concomitant administration of PCV7 with MMR, varicella and Hib as part of the
      recommended immunization schedule for children 12-15 months of age.

PMID- 16567982
TI  - Immunogenicity and boosting after a reduced number of doses of a pneumococcal
      conjugate vaccine in infants and toddlers.
AB  - BACKGROUND: The minimum number of doses of pneumococcal conjugate vaccine
      required for protection is not known. We studied the immunogenicity of a reduced
      schedule in infants and toddlers. METHODS: U.K. infants were given either 2 or 3
      doses (at 2 and 4 or 2/3/4 months of age) of a 9-valent pneumococcal conjugate
      vaccine (9VPCV) followed by boosting at 12 months of age. In a separate study,
      toddlers (12 months) received 1 or 2 doses (2 months apart) of 9VPCV followed by
      pneumococcal polysaccharide vaccine at 18 months of age. RESULTS: For infants,
      serotype-specific IgG geometric mean concentrations were similar post-primary
      immunization between the groups with both showing avidity maturation and similar
      booster responses. For toddlers, the primary response to 4 of the 9 serotypes was
      lower in the 1- compared with the 2-dose group (type 6B, 0.77 versus 7.1; type
      14, 4.67 versus 14.98; type 19F, 5.05 versus 7.75; type 23F, 2.48 versus 5.05),
      although for all serotypes booster responses were similar between groups, and the
      postprimary responses in the 1-dose group were at least as high as those after
      infant immunization. CONCLUSIONS: The 2-dose infant priming schedule of 9VPCV is
      comparable with the 3-dose schedule and may thus be equally protective, whereas 1
      dose in toddlers may suffice for a catch-up.

PMID- 16567983
TI  - Comparison of human metapneumovirus, respiratory syncytial virus and influenza A
      virus lower respiratory tract infections in hospitalized young children.
AB  - BACKGROUND: We compared the clinical and demographic features of children with
      lower respiratory tract infection (LRI) caused by human metapneumovirus (HMPV),
      respiratory syncytial virus (RSV) and influenza A virus and sought to determine
      whether coinfection by HMPV and other respiratory viruses leads to increased
      disease severity. METHODS: Nasal wash specimens were prospectively obtained from
      516 children hospitalized for LRI during a 1-year period and tested for the
      presence of HMPV by reverse transcription-polymerase chain reaction and for RSV
      and influenza A by direct immunofluorescence. RESULTS: HMPV was detected in 68
      (13%) patients and was the third most common viral pathogen; 16 of 68 HMPV
      positive children (24%) had coinfection with other respiratory viruses
      (HMPVco).HMPV patients were older than RSV patients (17.6 +/- 16.8 months versus
      10.5 +/- 11.8 months, P = 0.02). HMPV was associated with wheezing and hypoxemia
      at a rate similar to that of RSV and higher than that of influenza A. Atelectasis
      was more common among HMPV (40%) than among RSV and influenza patients (13%, P <
      0.05 for each). HMPV infection was more often associated with a diagnosis of
      pneumonia than RSV and influenza A and was more often associated with a diagnosis
      of asthma and less often associated with a diagnosis of bronchiolitis than RSV
      infection (P < 0.05 for each), even when corrected for age. Children with HMPVco
      had a higher rate of gastrointestinal symptoms but did not show a more severe
      respiratory picture. CONCLUSIONS: The clinical pattern of HMPV more closely
      resembles that of RSV than that of influenza A LRI, yet the differences in age,
      radiographic findings and clinical diagnosis suggest that HMPV pathogenesis may
      differ from that of RSV.

PMID- 16567984
TI  - Growth of human immunodeficiency virus-uninfected children exposed to perinatal
      zidovudine for the prevention of mother-to-child human immunodeficiency virus
      transmission.
AB  - BACKGROUND: Perinatal human immunodeficiency virus (HIV) prevention programs have
      been implemented in several countries, and many children have been or will be
      exposed to antiretrovirals in utero and during their first weeks of life.
      Although reducing substantially the number of infected children, the potential
      adverse consequences of these treatments on the health of HIV-uninfected children
      need to be assessed. OBJECTIVE: To investigate the impact of in utero and
      postnatal zidovudine exposure on the growth of HIV-uninfected children born to
      HIV-infected women. METHODS: We used data prospectively collected in 1408 live
      born children participating in a clinical trial comparing zidovudine regimens of
      different durations to prevent perinatal transmission in Thailand (PHPT-1). We
      used a linear mixed model to analyze the anthropometric measurements (weight for
      age, height for age and weight for height Z-scores) until 18 months of age
      according to zidovudine treatment duration (mothers, <7.5 weeks versus more;
      infants, 3 days versus >4 weeks). RESULTS: Children exposed in utero for >7.5
      weeks had a slightly lower birth weight (Z-score difference, 0.08; P = 0.003).
      However, zidovudine exposure had no effect on the evolution of Z-scores from 6
      weeks to 18 months of age. CONCLUSIONS: Although a longer in utero zidovudine
      exposure may have had a negative impact on birth weight, the magnitude of this
      effect was small and faded over time. Neither the total nor the postnatal
      duration of exposure was associated with changes in infant Z-scores from 6 weeks
      to 18 months of age.

PMID- 16567985
TI  - Comorbidities and mortality among children hospitalized with diarrheal disease in
      an area of high prevalence of human immunodeficiency virus infection.
AB  - PURPOSE: To describe the profile of comorbidities in children admitted with
      diarrhea to an urban hospital with high human immunodeficiency virus (HIV)
      prevalence in South Africa and to examine the contribution of comorbidities to
      inpatient mortality. METHODS: Data from a retrospective random sample of 319
      children were extracted and analyzed from a total of 1145 children hospitalized
      for diarrhea in 2001. We used multiple logistic regression models to determine
      the independent effects of HIV infection, malnutrition, pneumonia and bacteremia
      on inpatient mortality. RESULTS: Overall 68% of the diarrheal admissions were
      classified as HIV-infected and 61% were classified as malnourished, with 53%
      having evidence of both. HIV infection was strongly associated with malnutrition,
      pneumonia and bacteremia. Inpatient mortality was 14% [95% confidence interval
      (CI), 11-19%]. Mortality was higher among HIV-infected than among uninfected
      children [crude odds ratio (OR), 6.0; 95% CI 2.1-17.0]. History of low birth
      weight, previous admission, malnutrition, HIV infection, pneumonia, bacteremia,
      low hemoglobin, total white blood cell count and serum albumin were significant
      predictors of mortality in univariate analyses. After adjustment, severe
      malnutrition (OR 2.1; 95% CI 1.0-4.9), bacteremia (OR 2.9; 95% CI 1.2-7.2) and
      pneumonia (OR 3.9; 95% CI 1.3-12.0) remained independent predictors of mortality,
      whereas the association between HIV infection and mortality was significantly
      diminished (OR 4.0; 95% CI 0.8-18.1). CONCLUSION: In a setting of high HIV
      prevalence, malnutrition, bacteremia and pneumonia contribute independently to
      death in children hospitalized with diarrheal disease.

PMID- 16567986
TI  - Retrospective study of pediatric facial cellulitis of odontogenic origin.
AB  - OBJECTIVES: The aims of this retrospective study were to investigate the clinical
      characteristics of pediatric facial cellulitis of odontogenic origin and to
      compare the clinical differences between upper and lower facial infections and
      between genders. METHODS: Fifty-six children (28 boys and 28 girls) diagnosed
      with facial cellulitis of odontogenic origin during the year 2003 were selected
      for study. The average age was 5.72 +/- 2.70 years. Clinical investigations
      included sex, location of cellulitis, peak occurrence month, symptoms of
      infection, preference of first visit, hospitalization status, timing of surgical
      or dental interventions, need for incision and drainage, source of infection, and
      management of the primary odontogenic origin. Children were divided into upper
      face and lower face groups depending on the location of the infection. The chi
      and Student t tests were computed to assess the differences in the various study
      variables between upper and lower face infections and gender. RESULTS: Upper and
      lower face infections were reported in 57.1 and 42.9% of children, respectively.
      The source of infection was mostly from the deciduous posterior teeth. The
      clinical symptoms included a frequent toothache before swelling, and less
      commonly fever and trismus. Hospitalization was needed in 53.6% of the patients,
      and the mean length of hospitalization was 5.03 +/- 3.80 days. Surgical
      intervention such as incision and drainage was needed in only 25% of the cases.
      The majority of the patients had either surgical or dental interventions after
      subsidence of the swelling. The peak occurrence month was February. The source of
      infection in the upper face infections was significantly different from that of
      lower face infections (P < 0.01). Other study variables were not statistically
      significant for upper and lower face infections (P > 0.05). CONCLUSIONS: The
      differences in upper and lower face infections and differences in gender were not
      clinically significant. Surgical or dental interventions can be delayed through
      the proper use of antibiotics. With correct diagnosis, antibiotic treatment and
      appropriate timing for surgical or dental interventions, rapid resolution of the
      infection is expected.

PMID- 16567987
TI  - Clinical and molecular epidemiology of community-acquired methicillin-resistant
      Staphylococcus aureus infections among children with risk factors for health care
      associated infection: 2001-2003.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has recently
      emerged as a common cause of infection in children in many parts of the world.
      The epidemiology of community-acquired MRSA (CA-MRSA) among healthy children has
      been recently described. However, little is known about CA-MRSA in children with
      underlying medical conditions. OBJECTIVE: To compare the clinical and molecular
      epidemiology of CA-MRSA in children with and without risk factors for health care
      associated infections (RF-HAI). METHODS: We conducted a 3-year retrospective
      cohort study of children with CA-MRSA infection. RF-HAI, including
      hospitalization within the past year, indwelling medical devices or chronic
      medical condition, were identified by chart review. Genetic relatedness of CA
      MRSA strains was assessed by pulsed field gel electrophoresis. Polymerase chain
      reaction was used to detect Panton-Valentine leukocidin and determine
      staphylococcal chromosomal cassette carrying the mecA methicillin-resistant gene
      (SCCmec) type. RESULTS: We identified 446 episodes of community-acquired S.
      aureus infections, of which 134 (30%) were caused by MRSA. During the 3-year
      study period, the proportion of S. aureus infections caused by MRSA rose from 15%
      (12 of 80) to 40% (93 of 235) (P < 0.001) with the increase noted predominately
      in children with skin and soft tissue infections. RF-HAI were identified in 56
      (42%) patients with CA-MRSA. Among subjects with CA-MRSA, children with RF-HAI
      were more likely to have had an invasive infection than healthy children (32%
      versus 5%; P < 0.001). CA-MRSA isolates from children with RF-HAI were similar to
      those without RF-HAI; all laboratory-retained CA-MRSA isolates harbored the
      SCCmec type IV cassette, and almost all isolates were susceptible to trimethoprim
      sulfamethoxazole and clindamycin. However, pulsed field gel electrophoresis
      revealed greater molecular diversity among CA-MRSA isolates recovered from
      children with RF-HAI compared with those from otherwise healthy children (P =
      0.001). Additionally CA-MRSA isolates from children with RF-HAI were less likely
      to contain sequences for Panton-Valentine leukocidin (P < 0.001) and more likely
      to be resistant to 3 or more classes of antibiotics (P = 0.033). CONCLUSION: CA
      MRSA strains recovered from children with RF-HAI were phenotypically similar to
      those recovered from healthy children The absence of SCCmec type II or III MRSA
      among children with RF-HAI suggests that CA-MRSA strains might have become
      endemic within pediatric health care facilities.

PMID- 16567988
TI  - Three-year surveillance of community onset health care-associated staphylococcus
      aureus infections in children.
AB  - BACKGROUND: Staphylococcus aureus causes skin and soft tissue or invasive
      infections in children in the community, in the hospital or in other ways
      associated with the health care system (HCA). METHODS: Prospective community
      acquired S. aureus infection surveillance at Texas Children's Hospital was
      initiated on August 1, 2001. Community onset HCA (CO HCA) infections were
      identified. Demographic and clinical data were collected. Antibiotic
      susceptibilities were determined. Data were analyzed by chi or Student's t test.
      CO HCO-isolates were characterized by pulsed field gel electrophoresis and
      staphylococcal chromosomal cassette carrying the mecA methicillin-resistant gene
      (SCCmec) typing. RESULTS: From August 1, 2001 to July 31, 2004, 61.5% of 322 in
      year 1, 62.9% of 259 in year 2 and 56.9% of 318 in year 3 of CO HCA isolates were
      methicillin-resistant S. aureus (MRSA). Among the CO HCA-MRSA isolates, 8.9% of
      542 were from children with invasive infections compared with 24.1% of 357 CO HCA
      methicillin-susceptible S. aureus (MSSA; P < 0.001). Sixty-six percent of
      children with CO HCA-S. aureus isolates were admitted to the hospital.
      Clindamycin resistance increased over the 3 years (CO HCA-MRSA, from 3.5% to
      18.8%, P < 0.001; CO HCA-MSSA, from 3.2% to 10.2%, P = 0.053). Thirty-three of 35
      (94.3%) CO HCA-MRSA carried SCCmecIV; 30 were USA300. Only 3 of 35 MSSA were
      related to USA300 by pulsed field gel electrophoresis. CONCLUSIONS: CO HCA-S.
      aureus infections remained steady over the 3-year study at Texas Children's
      Hospital. Clindamycin resistance increased >4-fold for CO HCA-S. aureus isolates
      over the 3 years and is no longer appropriate for empiric treatment of invasive
      infections suspected to be caused by CO HCA-MRSA at our hospital. In our setting,
      CO HCA-MRSA infections are steady in number despite substantial increases in
      community-acquired MRSA infections and both being related to the same clone.

PMID- 16567989
TI  - Human metapneumovirus infection in young children hospitalized with respiratory
      tract disease.
AB  - BACKGROUND: Human metapneumovirus (hMPV) is a newly recognized pathogen
      associated with respiratory tract disease (RTD). OBJECTIVES: To evaluate the
      incidence of hMPV infection in children hospitalized with RTD and to analyze the
      virologic and clinical features of hMPV infection. STUDY DESIGN: All children
      younger than 5 years of age hospitalized for RTD were included in this 1-year
      prospective study. hMPV was detected in nasopharyngeal secretions by reverse
      transcription polymerase chain reaction. The hMPV F gene amplification products
      were sequenced, and a phylogenetic tree was constructed. Samples were also tested
      for other respiratory viruses by both direct immunofluorescence assay and virus
      culture. RESULTS: hMPV, detected in 50 of 589 (8.5%) children, represented the
      second leading cause of RTD after respiratory syncytial virus (RSV). Infections
      with hMPV occurred mainly between December and April. hMPV isolates clustered
      into the 4 subgroups (A1, A2, B1 and B2) currently recognized; the majority (72%)
      of hMPV isolates belonged to subgroup A1. Among the 35 children infected with
      hMPV alone, 23 (65.7%) had bronchiolitis, 5 (14.3%) had pneumonia, 2 (5.7%) had
      asthma exacerbation and 5 (14.3%) had a limited upper RTD. Fifteen (30%) of the
      hMPV-infected children were coinfected with RSV. As compared with children
      infected with hMPV or RSV alone, duration of hospitalization and requirement for
      supplemental oxygen were increased in the hMPV/RSV-coinfected children.
      CONCLUSIONS: hMPV is a frequent cause of RTD in young children. hMPV/RSV
      coinfection is frequent and could be more severe than a single hMPV or RSV
      infection.

PMID- 16567990
TI  - Epidemiology of pertussis.

PMID- 16567991
TI  - Introduction of tetanus toxoid and reduced diphtheria toxoid vaccines in the
      United States.

PMID- 16567993
TI  - Safety and immunogenicity of live varicella virus vaccine in children with human
      immunodeficiency virus type 1.
AB  - Live varicella virus vaccine was administered to 10 stable human immunodeficiency
      virus type 1 (HIV-1)-infected children. Subjects were monitored for adverse
      reactions, HIV-1 plasma levels, CD4 T cell counts and immune responses. The
      vaccine was well-tolerated. Varicella-zoster virus-specific lymphocyte
      proliferative responses were detected in all subjects by 4 weeks and in 9 of 10
      subjects 1 year after vaccination.

PMID- 16567992
TI  - Low immunologic response to highly active antiretroviral therapy in naive
      vertically human immunodeficiency virus type 1-infected children with severe
      immunodeficiency.
AB  - We conducted a retrospective study to analyze the CD4 recovery of naive
      vertically human immunodeficiency virus-infected children with severe
      immunodeficiency who were followed up during at least 4 years of receiving highly
      active antiretroviral therapy (HAART). Children with baseline CD4 of <15% did not
      reach a mean CD4 of > or =25% after the 4th year on HAART. We conclude that
      starting HAART after severe immunosuppression of naive HIV-infected children may
      not be effective for recovery of normal %CD4.

PMID- 16567995
TI  - Impact of the quebec school-based hepatitis B immunization program and potential
      benefit of the addition of an infant immunization program.
AB  - Ten years after a school-based hepatitis B immunization program was implemented,
      we conducted a study to assess the impact of the program, vaccine failures, risk
      factors and the number of cases potentially preventable by the addition of an
      infant vaccination program. The preteen vaccination program is highly effective.
      An infant immunization program would bring additional benefits.

PMID- 16567994
TI  - Active epidemiologic surveillance of pneumonia and invasive pneumococcal disease
      in ambulatory and hospitalized infants in Cordoba, Argentina.
AB  - Active surveillance of ambulatory and hospitalized children 2-23 months old in
      Cordoba, Argentina for invasive pneumococcal disease and radiographically
      confirmed "obvious" pneumonia revealed annual incidences of 206.8 and 2422 cases,
      respectively, per 100,000 children. The invasive pneumococcal disease incidence
      was substantially higher than those previously reported from Latin America and
      Europe.

PMID- 16567996
TI  - Extensive swelling reaction associated with diphtheria and tetanus toxoids and
      acellular pertussis vaccine.
AB  - Although extensive swelling reactions in the injected limb after the
      administration of diphtheria-tetanus toxoid-acellular pertussis vaccine have been
      reported previously, to our knowledge, computerized tomography images of this
      entity have not been published. A 4-year-old boy with extensive swelling after
      vaccination with diphtheria-tetanus toxoid-acellular pertussis vaccine is
      presented.

PMID- 16567997
TI  - Early onset Morganella morganii sepsis in a newborn infant with emergence of
      cephalosporin resistance caused by depression of AMPC beta-lactamase production..
AB  - A preterm infant with early onset Morganella morganii sepsis was treated with
      cefotaxime and gentamicin after confirmation of antimicrobial susceptibility. The
      infant developed persistent ventriculitis caused by the emergence of a cefotaxime
      resistant Morganella variant with derepression of its AmpC beta-lactamase. When
      choosing antibiotic therapy, the risk of development of resistance to
      cephalosporins should be considered in infections caused by M. morganii and other
      Gram-negative organisms with inducible AmpC beta-lactamases.

PMID- 16567998
TI  - Recurrent central nervous system blastomycosis in an immunocompetent child
      treated successfully with sequential liposomal amphotericin B and voriconazole.
AB  - Central nervous system involvement in infection with Blastomyces dermatitidis is
      uncommon, except in immunocompromised patients. We report a case of central
      nervous system blastomycosis occurring 18 months after treatment of pulmonary
      blastomycosis in an immunocompetent child. Our patient was successfully treated
      sequentially with liposomal amphotericin B followed by oral voriconazole without
      need for surgical resection.

PMID- 16567999
TI  - Intracranial aspergillosis in children successfully treated with antifungal
      therapy and surgical intervention.
AB  - Invasive aspergillosis is an uncommon but often lethal complication in
      immunocompromised patients. Despite the progress obtained with new antifungal
      drugs, intracranial aspergillosis often requires a combined medical and surgical
      approach. Most cases previously reported in immunocompromised children were
      fatal. We describe 4 immunosuppressed children with intracranial aspergillosis
      successfully treated with surgery and antifungal long-term therapy.

PMID- 16568001
TI  - Pneumococcal resistance in the postvaccine era.

PMID- 16568000
TI  - Neuropsychiatric reaction induced by abacavir in a pediatric human
      immunodeficiency virus-infected patient.

PMID- 16568002
TI  - Favorable midterm results of total hip arthroplasties with a lateral flare
      uncemented stem.
AB  - Uncemented stems have been advocated for primary total hip arthroplasties in the
      young active population. We evaluated the clinical and radiographic results of
      total hip arthroplasties with a customized lateral flare cementless femoral stem
      in a prospective, consecutive series of 35 patients (40 hips) younger than 55
      years at the time of surgery and who were followed up for an average of 9.2 years
      (range, 5.7-12.2 years). The study group comprised 20 men and 15 women with an
      average age of 45.2 years (range, 30-55 years). One patient had aseptic loosening
      of the stem and one patient had a deep infection. The mean preoperative Harris
      hip score was 47 and at the latest followup it was 97. The mean axial migration
      was 0.51 mm. Femoral osteolysis was found to be circumscribed to the proximal
      femur in Gruen Zones 1 (15%) and 7 (8%) in patients with accelerated polyethylene
      wear. Radiographic changes consistent with new bone apposition under the lateral
      flare of the stem in Zones 2, 6, and 7 were found in 73% of the cases. Our data
      suggest a custom lateral flare stem for primary arthroplasties in the younger
      patient population achieves excellent clinical results with a low rate of aseptic
      loosening. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series).

PMID- 16568003
TI  - Periprosthetic fractures after total knee arthroplasties.
AB  - The management of periprosthetic fracture around the knee remains a challenging
      problem. The objective of this article was to review the general concepts,
      treatment algorithms, and the overall treatment outcomes of femoral and tibial
      periprosthetic fractures after total knee arthroplasty. This article aimed to
      highlight the deficiencies of the current classification systems that fail to
      provide a guideline for selection of appropriate treatment options. We proposed a
      new classification system for periprosthetic femoral fractures that takes into
      account the status of the prosthesis, the quality of distal bone stock, and the
      reducibility of the fracture. Type I fractures are those occurring in patients
      with good bone stock with the prosthesis being fixed and well positioned. Type IA
      fractures are either nondisplaced or easily reducible and can be treated
      conservatively. Type IB fractures are irreducible and require reduction and
      internal fixation. Type II fractures are defined as those occurring also in
      patients with good bone stock and being reducible, but either the components are
      loose or malpositioned. These fractures are treated by revision arthroplasty.
      Type III fractures are reducible or irreducible fractures that occur in patients
      with poor bone stock and in the vicinity of loose or malpositioned components.
      These fractures are treated by distal femoral replacement. LEVEL OF EVIDENCE:
      Therapeutic study, level V (expert opinion). See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 16568004
TI  - Hybrid component fixation in revision total knee arthroplasty.
AB  - We retrospectively analyzed the midterm survivor rate of revision total knee
      arthroplasty using hybrid stem fixation. We included 33 patients, 21 women and 12
      men with an average age of 68 years (range, 57-80 years). Revision was performed
      for aseptic loosening in 16 patients, aseptic loosening and knee instability in
      five patients, instability in seven patients, infection in three patients, and
      postoperative stiffness and pain in two patients. The average follow-up was 38
      months. Three knees (9%) were revised during the follow-up period. Two patients
      (6%) underwent revision for aseptic loosening and one patient (3%) for deep
      implant infection. The average knee score improved from 42 points (range, 10 to
      60) to 83 points (range, 60 to 100). The average functional score improved from
      48 points (range, 15-65 points) to 76 points (range, 46-99 points). All patients
      had no pain (13%) or moderate/occasional pain (87%) during walking. The average
      ROM improved from 94 degrees (range, 45 degrees-125 degrees) to 105 degrees
      (range, 70 degrees-125 degrees). Hybrid component fixation is a useful treatment
      option in revision total knee arthroplasty. The revision rate for aseptic
      loosening within a three year follow-up is 6%. LEVEL OF EVIDENCE: Therapeutic
      study, level IV (case series). See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 16568007
TI  - [In vivo functional microspectroscopy of cells and tissues].
AB  - The interaction between living matter and optical spectra (Raman, infrared,
      fluorescence spectroscopy) can be used to characterize simple or complex
      biomolecular systems. At the cell and tissue level, these microspectroscopic
      techniques can be used to construct descriptors of molecular or supramolecular
      (nucleic acids, proteins, lipids, etc.) function in a given biological situation
      (healthy or pathological tissue, normal or pathological cell, induction of
      cytotoxicity, apoptosis or differentiation, presence or not of a resistance
      phenotype, etc.) At the present time vibrational spectroscopy appears to be a
      particularly powerful technique for characterization of the early phases of
      pathological processes occurring within given cells or tissues. It could be used
      to develop tools for early diagnosis and prediction of therapeutic response.

PMID- 16568005
TI  - Surgical treatment and customized rehabilitation for stiff knee arthroplasties.
AB  - Treating patients who have arthrofibrotic or stiff knees after total knee
      arthroplasty can be difficult. Treatment with arthroscopic debridement,
      arthrolysis of adhesions with polyethylene spacer exchange, or complete revision
      arthroplasty often has led to less than optimal range of motion and functional
      outcomes. We used a combination of surgical arthrolysis and an intensive
      postoperative rehabilitation protocol, including functional bracing, to treat
      this condition. We then retrospectively reviewed 18 knees in 17 patients who had
      stiff knees after total knee arthroplasty with no other detectable clinical or
      radiographic abnormalities, at a mean followup of 30 months. Seventeen knees
      (94%) had gains in knee range of motion with a mean increased range of motion of
      31 degrees. Although 16 of 17 patients had clinical improvement and were
      satisfied with the procedure, only (2/3) of the patients (12 of 18 patients) had
      excellent or good Knee Society objective scores. This combined surgical and
      rehabilitation method can lead to an increased range of motion. All patients
      improved clinically, but good functional results were less predictable. The
      authors think treatment of these difficult knees should be aimed at soft tissue
      operative releases supplemented by an intensive rehabilitation protocol. LEVEL OF
      EVIDENCE: Therapeutic study, level IV (prospective study). See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 16568008
TI  - [Role of matrikins in melanoma progression].
AB  - Expression of melanoma invasiveness, ultimately leading to the formation of
      metastases, requires that cancer cells break through the successive skin barriers
      (dermo-epidermal junction, dermis) constituted of various extracellular matrix
      constituents. In order to facilitate their progression, melanoma cells express,
      in concert with stromal cells, a group of proteolytic systems which degrade this
      extracellular structures. However, proteolysis of basement membrane, collagen or
      elastic fibers can uncover cryptic sites or/and liberate matrix fragments whose
      properties appeared distinct from their intact macromolecule counterparts. Those
      fragments, called matrikines, are able to empede or to accelerate melanoma
      progression ex vivo and in vivo. Non-collagenous domains of basement membrane
      collagens, which behave like potent "matstatins", are seen as potential
      pharmacological agents in melanoma.

PMID- 16568009
TI  - [Anti-tumor immunotherapy against multidrug resistance].
AB  - Overexpression of a membrane glycoprotein (P170) represents the most common
      multidrug resistance (MDR) mechanism in cancer therapy. Specific autoantibodies
      to extracellular loops 1, 2 and 4 of murine P170 are elicited in mice using
      palmitoylated synthetic peptides reconstituted in liposomes with or without Lipid
      A and resuspended in alum. IgM antibodies are detected 14 days following the
      first injection and IgG1 become predominant after the third challenge. Animals do
      not show any autoimmunity symptoms or induced toxicity up to 18 months after the
      immunization. Previous immunizations of mice using liposomes with mdr1 peptides
      efficiently improve chemotherapy with doxorubicin and vinblastine against P388 R
      cells with a 77% increase of survival half time in the immunized group. Sera from
      immunized mice are also effective in reducing cellular resistance to vinblastine
      and doxorubicin in vitro. Taken together these data suggest that this
      immunization approach might have potential clinical applications.

PMID- 16568011
TI  - [Regeneration of injured airway epithelium].
AB  - The airway surface epithelium is frequently injured by microorganisms and viruses
      due to its permanent contact with the external medium. Following injury, the
      epithelium is able to repair itself and regenerate through several mechanisms
      including spreading and migration of basal cells, cell proliferation and
      differentiation. The cellular and molecular factors involved in wound repair and
      epithelial regeneration interact closely, implying the participation of
      cytoskeleton proteins and integrins receptors, matrix metalloproteinases and
      their inhibitors as well as cytokines and growth factors secreted by airway
      epithelial and mesenchymal cells. The spatio-temporal modulation of the pro
      inflammatory cytokines such as IL-8, and MMPs (MMP-9 and -7) during the different
      steps of regeneration suggests that the matrix and secretory environment are
      markedly involved in these mechanisms and that their dysregulation may induce
      remodeling of the airway mucosa. A better knowledge of the mechanisms involved in
      airway epithelium regeneration may pave the way to regenerative therapeutics
      allowing the reconstitution of a functional airway mucosa in numerous respiratory
      diseases such as cystic fibrosis, chronic obstructive pulmonary diseases and
      bronchiolitis.

PMID- 16568010
TI  - [Telomeres and telomerase, new targets for anticancer chemotherapy].
AB  - Telomeres are composed of single-strand DNA rich in guanine which can adopt
      particular structures such as T-loop or G-quadruples, a four-strand DAN structure
      formed by guanine repeats. Telomeric single-strand DNA is the substrate of
      telomerase, an enzyme necessary for telomeric replication which is suppressed in
      most cancer cells and which participates in tumor genesis. The formation of a
      telomeric G-quadruplex blocks telomerase activity and offers an original strategy
      for new anti-cancer agents. Using an original approach combining rational
      screening and synthesis, several series of compounds have been identified which
      specifically bind to the telomeric quadruplex. These derivatives, called "G
      quadruplex DNA ligands", are able to block telomeric replication in cancer cells
      and provoke replicative senescence and/or apoptosis after a few cell cycles. Our
      team is working on characterizing the cellular and molecular mechanisms of action
      of these ligands. Using mutant cell models resistant to these ligands or
      expressing a protein cuff covering the telomere in tumor lines, we have
      demonstrated that the telomere is the principal intracellular target of action of
      these compounds and the implicit existence of the G-quadruplex structure. In
      collaboration with academic and industrial partners, optimization of these
      ligands to develop pharmacologically active products should enable in vivo
      validation of a new therapeutic concept.

PMID- 16568012
TI  - [Cell-host-parasite interactions: biodiversity, pathogenesis, environment].
AB  - The apicomplexan Toxoplasma gondii, an obligate intracellular parasite, can
      infect humans and a wide range of vertebrates leading to toxoplasmosis. This
      generally benign affection can causes severe life-threatening disease,
      particularly in immunocompromised patients and in children with congenital
      toxoplasmosis. Our research team works on cell-host-parasite interactions by
      studying biodiversity, pathogenic mechanisms and environment. We search to
      identify prognostic factors of disease and markers of resistance. This project is
      an integral part of our Research Institute (IFR53) which receives support from
      the Toxoplasma Biological Resource Center for constituting a bank of well
      characterized toxoplasma isolates for genotyping, clinical and epidemiological
      data. The involvement of metalloproteinases implicated during monocytic cell
      invasion and identification of ABC transporter proteins in T. gondii, factors
      implicated in resistance, need to be explored.

PMID- 16568013
TI  - [Paleoparasitology: host-parasite relationship in a historical and
      paleoenvironmenal context].
AB  - Paleoparasitology of the ancient world has mainly concerned the study of latrine
      sediments, coprolites collected from mummified bodies or archeological strata,
      mostly preserved by natural conditions. The well-preserved conditions of helminth
      eggs have allowed paleoepideological approaches and application of immunological
      techniques for the detection of protozoan palaeoantigens.

PMID- 16568015
TI  - [Regenerating agents (RGTAs): a new therapeutic approach].
AB  - RGTAs, or ReGeneraTing Agents constitute a new class of medicinal substance that
      enhance both speed and quality of tissue healing and leading in some case to a
      real tissue regenerating process. RGTAs consist of chemically engineered polymers
      adapted to interact with and protect against proteolytic degradation of cellular
      signaling proteins known as growth factors, cytokines, interleukins, colony
      stimulating factors, chemokines, neurotrophic factors etc. Indeed almost all
      these proteins of cellular communication are naturally stored in the extra
      cellular matrix interacting specifically with the heparan sulfates or HS. After
      tissue injury of any cause, cells die liberating glycanases and proteases
      inducing first HS degradation then liberation of the cytokines which in turn are
      susceptible to degradation as they are no longer protected. By replacing the
      natural HS, RGTAs will protect cytokines from proteolyses as they are liberated
      from the matrix compartment matter in the wound. This spatio-temporal selective
      protection of cytokines results in a preservation of the natural endogenous
      signaling of a tissue and is reflected by spectacular tissue regeneration or by a
      very greatly improved tissue repair. These observations indicate that mammals
      have an unexpected ability to regenerate and that RGTA helps to reveal this
      capacity. The aim of OTR3 is to develop RGTA into a drug to treat specific tissue
      lesions.

PMID- 16568014
TI  - [Nano-biocaptures for research and diagnostics in inflammation diseases and
      cancer].
AB  - As part of the ongoing search for ways to decrease the mortality of different
      pathological conditions related to cancer and inflammatory diseases,
      nanotechnologies currently under evaluation offer potentially attractive tools
      for innovative methodologies for early diagnosis, new bioimaging techniques and
      therapeutic strategies. Nano-tools can be employed for various functions, such as
      the detection of lesions at very early stages of disease development, extremely
      precise anatomical localization, or evaluation of the efficacy of medications
      specifically targeted against cells and pathological tissues. We have synthesized
      homogeneous CdSe/ZnS (core/shell) highly fluorescent nanocrystals (NC) detectable
      as individual nanoparticules with a routine fluorescent microscope. These NC are
      at least 10-fold brighter than the best organic fluorophores and at least 1000
      fold more stable against photobleaching than AlexaFluor, for example. When
      conjugated with proteins, DNA or with drugs, NCs may be excited with the light of
      any wavelength from UV through visible spectral region providing a range of
      fluorescence colors depending on their diameter. These properties provide
      excellent perspectives for high through-put multiplexing and long-term tracking
      of labeled precursors for days or even weeks. We present here NC applications for
      ultrasensitive detection of p-glycoprotein, cytokeratins, LCA, Ki67, etc. both on
      the cellular level and in pathological human surgical specimens.

PMID- 16568016
TI  - [Laparoscopic colon-sigmoid resection with mesenteric artery preservation for
      diverticular disease].
AB  - AIM: About 2/3 of the Western population over the age of 80 years are affected by
      colic diverticulosis; 25% will develop diverticular disease with or without
      complications: fistula, obstruction, pericolic abscess, free perforation or
      hemorrhage. Laparoscopic approach for benign diseases of the colon such as
      diverticulosis, Chrohn's disease, etc. is unanimously considered as a very
      effective procedure. We have performed a retrospective analysis of 9 years with
      laparoscopic approach of the diverticular disease. The purpose of this study was
      to determine the feasibility, safety and benefits of laparoscopic approach.
      METHODS: From May 1994 to November 2002, 69 patients affected by non-complicated
      diverticular disease, were treated laparoscopically, at the Mininvasive Surgery
      Department of Spoleto. In the same period other 213 patients suffering from
      cancer of the colon-rectum were operated through laparoscopic surgery. A
      colosigmoid resection with mesenteric inferior artery preservation was performed
      in 46 cases (67%). RESULTS: We have performed only a laparoscopic colectomy
      technique (no hand-assisted procedures); the convertion rate was of 7.2%, the
      mean operative time was 145 min, no intraoperative complications were observed
      and finally the mean hospital stay was of 7.4 days (6-9). The postoperative
      complications were 1 case of infection of the umbilical scar and 1 case of
      pleural effusion with bronchopneumonia. CONCLUSIONS: Elective laparoscopic
      colectomy for diverticular disease is feasible, safe and gives very good results:
      minimum postoperative discomfort, rapid recovery, low mobility and postoperative
      stay, rapid return to normal activities. However, in some cases, this procedure
      can be extremely difficult because of previous inflammatory complications
      (adhesions, fistulas or stenosis), therefore, high surgical skills in
      laparoscopic-colic surgery are required.

PMID- 16568017
TI  - Surgical therapy for patients with extraesophageal symptoms of gastroesophageal
      reflux disease.
AB  - AIM: The last 20 years have seen a systematic reappraisal of the physiopathology
      and diagnosis of gastroesophageal reflux disease (GERD) and its associated
      typical symptoms, while less attention has been paid to correlating GERD with
      certain extraesophageal symptoms and the value of surgery for their treatment.
      The aim of this study was to determine the clinical and physiopathological
      features and the outcome of surgery, in a group of patients who underwent
      laparoscopic fundoplication for GERD with atypical symptoms, and to compare the
      results with another group of patients operated for GERD with typical symptoms.
      METHODS: Two hundred and forty-one patients were evaluated for GERD at our
      Digestive Physiopathology outpatients surgery from January 2001 to January 2003.
      Of the 36 patients who underwent laparoscopic fundoplication, 23 had the typical
      symptoms of GERD and 13 had atypical symptoms. Twelve months after surgery, these
      patients were compared in terms of 24-h pH monitoring, esophageal manometry,
      regression of symptoms and degree of satisfaction. RESULTS: Postoperatively,
      patients with atypical symptoms had a smaller increase in effective peristalsis
      (P = 0.06) and a more limited improvement in symptoms (54% vs 91%, P = 0.001),
      and they expressed less satisfaction with the surgical treatment (5.9 vs 8.2, P =
      0.003). CONCLUSIONS: The results of surgery in GERD patients with atypical
      symptoms are worse than in those with typical symptoms. A careful preoperative
      work-up, based on 24-h pH monitoring, is fundamental for patients with atypical
      symptoms, who also need to be informed of the high likelihood of surgery proving
      clinically unsuccessful.

PMID- 16568018
TI  - [Nearly total thyroidectomy: versus total thyroidectomy: our experience].
AB  - AIM: Generally, the classification of thyroidectomy as benign pathology is:
      multinodular toxic goitre, simple goitre, toxic adenoma, Base-dow disease,
      Hashimoto's tyroiditis Subtotal thyroidectomy provides for the removal of the
      gland except for a bilateral residue of about 6-10 g, near total thyroidectomy
      provides for the near total removal of the gland except for a residue inferior to
      5 grams. Near total thyroidectomy has taken the place of the subtotal
      thyroidectomy. METHODS: In two years, in our institute, there have been exeuted:
      96 near total thyrodectomies, 96 total thyroidetomies, 8 lobectomies ad two
      revues for recurrencies. RESULTS: In 2 cases there have been haemorrhagies after
      nearly total thyroidetomy. Only in 1 case we practiced tracheotomy for follicular
      carcinoma infiltering thiroidic cartilage. In 2 cases treated with nearly total
      thyroidetomy and in 4 cases treated with total thyroidetomy, there has been
      temporary hypoparathyroidism. In no case treared wih nearly total thyroidetomy
      and in 2 cases treated with total thyroidetomy, there has been permanent hypo
      parathyroidism. In 5 cases treated with total thyroidetomy and in no case treated
      with nearly total thyroidetomy, there has been, monolateral, temporary paralysis
      of the inferior laryngeal nerve that solved in 6 months for 3 patients and in 2
      months for 2 patients. CONCLUSIONS: There has not been permanent paralysis of the
      mono or bilateral inferior laryngeal nerve. Even if the surgical approach to the
      benign disease is now orientated to the total thyroidectomy, a more conservative
      surgery is, in our opinion, justified when a malignant pathology is excluded and
      considering also the low effect of recurrencies and hypothyroidism.

PMID- 16568019
TI  - [Sentinel lymph node procedure in thyroid carcinoma patients. Our experience].
AB  - AIM: How far to extend surgical treatment of papillary thyroid carcinoma (PTC) is
      still an open question. A contribution may derive from intraoperative lymphatic
      mapping because, in other malignancies, the procedure has become an important aid
      in defining lymph node status. The aim of this study was to evaluate the
      feasibility of sentinel lymph node (SLN) mapping performed by intratumoural
      injection of vital blue dye to guide nodal dissection in PTC. METHODS: One
      hundred and ten patients were selected for the study, all of them had a
      preoperative diagnosis of PTC, but no clinical or ultrasonographic evidence of
      nodal involvement. Following cervicotomy and exposition of the thyroid gland,
      vital blue dye was injected into the malignant thyroid nodule. Subsequently,
      total thyroidectomy and lymph node dissection were carried out, and the thyroid,
      the SLN(s) and the other lymph nodes were sent for frozen section and definitive
      histologic evaluation. RESULTS: Intraoperative lymphatic mapping located sentinel
      lymph nodes in 74 cases (67.3%); the SLN was detected in the laterocervical
      compartment (LC) in 4 cases (5.4%), with the ''sick'' of the CC. In 23 of these
      74 patients (31.1%) the SLN(s) were positive for micro-metastases and in 15 cases
      (65.2%) both the SLN and other resected nodes were found positive. In the 51
      cases in whom the SLN was disease-free, the other nodes were also negative. Of
      the 36 cases in whom the SLN was not detected, in 4 cases (11.1%) a parathyroid
      gland was stained and in 1 case (2.8%) fibroadipous tissue was stained. To date,
      of the 23 patients with positive-SLN 22 patients are living without disease
      (95.6%), 1 patient is living with disease (4.4%); all patients with negative SLN
      are living without disease; of the 36 patients without staining of the SLN, 35
      are living without disease (97.2%) and 1 patient is deceased for reasons
      different from PTC (2.8%). CONCLUSIONS: On the basis of this study, we underline
      some disadvantages in using Blue Patent V dye in SLN biopsy procedure as: a) the
      risk of disruption and interruption of the lymphatics from the tumour; b) blue
      dye uptake by a parathyroid gland which is successively mistakenly removed; c)
      the ''seak'' of the CC that doesn't permit to disclose SLN that lies outside the
      central compartment.

PMID- 16568020
TI  - [Biliodigestive anastomosis: case series and technical notes].
AB  - AIM: Biliodigestive anastomoses are widely used in the treatment of biliary
      obstruction. METHODS: A survey is presented of the personal case series treated
      during the last 5 years. Thirty biliodigestive anastomose have been performed
      both for neoplastic disease and for benign lesions. RESULTS: The biliodigestive
      anastomosis has been performed with the Blumgart's technique both for benign and
      malignant tumors. CONCLUSIONS: The authors point out that experience is of the
      utmost importance for the operation success. Major attention is paid to the
      surgical technique used for the biliodigestive anastomosis and a retrospective
      analysis is made.

PMID- 16568021
TI  - [Intraoperative transesophageal echocardiography in the endovascular treatment of
      thoracic aortic aneurysms].
AB  - AIM: Endovascular surgery is an efficacious alternative to conventional surgery
      in the treatment of descending thoracic aorta aneurysms. However, primary and
      delayed endoleaks are some endovascular technology's weak points. They are
      usually detected by angiography or angio CT, but many information may be obtained
      by transesophageal echocardiography (TEE) both as to endoleaks and to endograft's
      correct placement. Our purpose is to confirm, on the basis of our experience, the
      validity of this technique chosen both by us and by other groups with a wider
      casuistry. METHODS: We positioned endografts for the treatment of degenerative or
      post-traumatic aneurysms of the descending thoracic aorta using TEE, together
      with angiography, during surgery in 8 out of 9 patients. TEE was carried out on
      the same 8 patients also before surgery, and for some patients even in the follow
      up together with angio CT, after 6 and 12 months. RESULTS: In the situations
      where TEE was used we found 5 cases of endoleaks and 1 of these was not detected
      by angiography because of its small dimensions. All of these endoleaks were
      immediately corrected with more angioplasty or graft extensions; in a case, where
      we could not utilize the TEE, the problem solved spontaneously after 30 days as
      it was confirmed both by angiography and angio TC. The statistical analysis with
      the Student t test is significant for P < 0.005. CONCLUSIONS: We think that using
      TEE during the placement of an endograft on the descending thoracic aorta may
      help to obtain useful information in addition to those that we can obtain with
      angiography. Therefore, this may lead to improve the technique and to reduce
      possible both immediate or delayed complications.

PMID- 16568022
TI  - Amelanotic malignant melanoma of the esophagus. Report of a case.
AB  - Primary malignant melanomas of the esophagus are rare neoplasms with aggressive
      behavior and tendency to lymphatic and hematogenous spread. We report on a
      patient affected with a primary amelanotic melanoma of the esophagus synchronous
      to a squamous cell carcinoma of the epiglottis and treated by subtotal
      esophagectomy. A 58-year-old woman presented with a three-month history of
      dysphagia, retrosternal pain and weight loss. An upper gastrointestinal endoscopy
      revealed a 3 cm, non pigmented, polypoid mass of the middle esophagus and biopsy
      was consistent with undifferentiated carcinoma. Fiberoptic bronchoscopy revealed
      a 0.5 cm, polypoid lesion of the right aspect of the epiglottis consistent with a
      squamous cell carcinoma. The esophageal neoplasm was treated by subtotal
      esophagectomy while the squamous cell carcinoma of the epiglottis was referred to
      radiotherapy 1 month after surgery. Microscopy showed diffuse proliferation of
      anaplastic cells with multiple mitotic figures, marked nuclei and multilobulated
      nucleoli. The neoplasm stained positive for HBM-45 antigen and S-100 protein.
      Tumor stage was pT1N0M0. Review of patient's medical history and exploration of
      skin and mucous membranes failed to reveal malignant lesions and definitive
      diagnosis was primary amelanotic malignant melanoma of the esophagus. The patient
      died 16 months after surgery of disseminated disease. In conclusion the present
      case confirms that primary malignant melanomas of the esophagus have a dismal
      outcome even in cases of early-stage lesions amenable to surgical resection.

PMID- 16568023
TI  - Primary hyperparathyroidism related to a parathyroid adenoma: the dramatic
      clinical evolution of a misdiagnosed patient and its surgical solution.
AB  - Primary hyperparathyroidism is a clinical condition related to an excessive and
      abnormally regulated secretion of parathyroid hormone (PTH) from the parathyroid
      glands which is responsible for an alteration of the calcium and phosphorus
      metabolism. Parathyroid adenomas are the most important cause of primary
      hyperparathyroidism (80-85%). A case of parathyroid adenoma observed in a patient
      aged 47, admitted to the Emergency Medicine Department of our Hospital with a
      diagnosis of hypertensive crisis, cephalea, vomiting, and a clinical history of
      recurrent episodes of severe abdominal and renal pain, is presented. Lab data
      showed severe hypercalcemia and a progressive worsening of the renal function. A
      severe neurological involvement with stupor, derangement of mind, the arising of
      acute respiratory depression, lethargy compelled the colleagues to transfer him
      to the Intensive Care Unit; a neck ultrasonography showed a poor-echogenous area
      under the right thyroid inferior pole, with signs of vascularization. The suspect
      of a primary hyperparathyroidism related to a single adenoma of the parathyroid
      gland suggested a surgical treatment. A ''concise parathyroidectomy'' was
      performed. Our surgical approach was confirmed by the comparison of the
      preintervention and the post-intervention iPTH values: 2080 pg/mL (normal range:
      12-65 pg/mL) before excision vs 101 pg/mL after the removal. The histologycal
      exam reported a parathyroid adenoma with large areas with haemorrage. Three days
      after surgery the patient was in good general conditions. Patients affected by
      primary hyperparathyroidism are often misdiagnosed because their clinical
      conditions can create differential diagnosis problems with other diseases.
      However the surgical option remains the gold standard treatment.

PMID- 16568025
TI  - [Open radiofrequency liver resection: technical details].
AB  - AIM: Radiofrequency (RF) for the treatment of hepatic neoplasms can be performed
      through percutaneous, laparoscopic or open surgery. The aim of this study was to
      point out the details of the role of open RF (ORF). METHODS: Between November
      2002 and November 2003, we performed 13 ORFs. Seven patients had an association
      with chronic liver cirrhosis. With the aid of intraoperative single, internally
      cooled needle RF, 12 liver resections were performed (7 subsegmentectomies, 3
      segmentectomies, 1 left lateral lobectomy, and 1 right lobectomy). In 1 case RF
      was applied directly to the tumor lesion. In all cases ultrasonography (US) was
      performed intraoperatively, other lesions were found in 7.7% of the cases. RF
      energy was applied along the margins of the tumor to create <<zones of necrosis>>
      before resection with a scalpel. RESULTS: Average operating time for ORF alone
      was 74.4 minutes (range 30-115 minutes). Mean intraoperative blood loss during
      the procedure was 104 mL (range 25-250 mL), and blood transfusions were required
      in 3 patients. Mean hospital stay was 7.9 days (range 6-10 days). Only minor
      complications were found, and no mortality was observed. No liver recurrence was
      detected during mean follow-up of 6 months. CONCLUSIONS: This technique is
      suitable for patients who are at risk of bleeding because it offers a new method
      for transfusion-free resection, reducing postoperative complications and shorter
      long-term survival. Adequate follow-up is necessary to judge its true efficacy,
      in terms of recurrence and survival.

PMID- 16568024
TI  - [Cervical lymphorrea after nodal dissection: role of fasting based on clinical
      evidence].
AB  - The management of chylous fistula, subsequent to neck nodal dissection, includes
      either unstandardized conservative procedures and reoperation. The main reason of
      controversy in literature is probably due to the rarity (1-2.5%) of such
      troublesome complication due to inadvertent disruption of the thoracic duct
      itself or of its tributary branches. We report one case of severe cervical
      chylous fistula, occurred after left lateral dissection for advanced papillary
      thyroid carcinoma, and successfully restored by a conservative approach. None of
      the following treatment modalities was effective: pressure dressing, low-fat
      diet, octreotide, etilefrine, and local tetracycline sclerotherapy. Instead,
      fasting combined with total venous nutritional replacement was successful in
      curing the leak. It may be hypothesized that the beneficial effect on chyle
      production observed in the present patient in fasting condition, could be
      explained by a decrease of splancnic blood flow consequent to intestinal feeding
      rest. The other treatment procedures can be adjunctive methods with impredictable
      effect. As a standard approach with the aim to prevent and treat cervical
      lymphorrea, we suggest preoperatory fat meal, intraoperative search for milky
      leak by positive respiratory pressure, ligation of the thoracic duct (a mesh
      coverage when necessary) if inadvertently damaged, but not a systematic search
      for it. Moreover, according to the amount and the duration of the leakage,
      fasting combined with venous supplement by central or peripheral access, in
      combination with local treatment by sclerosing agents appears to be efficacious.
      In our opinion, neck reoperation or intrathoracic ligation of the thoracic duct
      represent the last therapeutic option of unresponsive or untractable cases.

PMID- 16568026
TI  - A lump in the neck: cervical bronchogenic cyst mimicking a thyroid nodule.

PMID- 16568027
TI  - [Peritoneal carcinomatosis due to ocular melanoma].

PMID- 16568028
TI  - [Retroperitoneal ''Ancient Schwannoma'': case report].

PMID- 16568029
TI  - CHST6 mutations in North American subjects with macular corneal dystrophy: a
      comprehensive molecular genetic review.
AB  - PURPOSE: To evaluate mutations in the carbohydrate sulfotransferase-6 (CHST6)
      gene in American subjects with macular corneal dystrophy (MCD). METHODS: We
      analyzed CHST6 in 57 patients from 31 families with MCD from the United States,
      57 carriers (parents or children), and 27 unaffected blood relatives of affected
      subjects. We compared the observed nucleotide sequences with those found by
      numerous investigators in other populations with MCD and in controls. RESULTS: In
      24 families, the corneal disorder could be explained by mutations in the coding
      region of CHST6 or in the region upstream of this gene in both the maternal and
      paternal chromosome. In most instances of MCD a homozygous or heterozygous
      missense mutation in exon 3 of CHST6 was found. Six cases resulted from a
      deletion upstream of CHST6. CONCLUSIONS: Nucleotide changes within the coding
      region of CHST6 are predicted to alter the encoded protein significantly within
      evolutionary conserved parts of the encoded sulfotransferase. Our findings
      support the hypothesis that CHST6 mutations are cardinal to the pathogenesis of
      MCD. Moreover, the observation that some cases of MCD cannot be explained by
      mutations in CHST6 suggests that MCD may result from other subtle changes in
      CHST6 or from genetic heterogeneity.

PMID- 16568030
TI  - Novel variants in the hotspot region of RP1 in South African patients with
      retinitis pigmentosa.
AB  - PURPOSE: Mutations in the hotspot of RP1 are reportedly responsible for 4-7% of
      autosomal dominant retinitis pigmentosa (ADRP) in the United States, Canada, and
      Europe. South Africa (SA) has unique subpopulations and a comparatively low
      observed frequency of rhodopsin mutations, which lead to this investigation of
      the contribution of RP1 mutations to the ADRP disease burden in SA. METHODS:
      Fifty-seven affected, unrelated South African individuals with ADRP were selected
      for mutation screening of the RP1 hotspot, using denaturing high performance
      liquid chromatography (HPLC). Variants were identified by direct sequencing,
      after which cosegregation analysis and population frequency studies were
      performed using restriction fragment length polymorphism analysis, nondenaturing
      HPLC, or denaturing HPLC. RESULTS: Three mutations were identified, including two
      novel sequence variations and the common Arg677X mutation. A wide spectrum of
      disease severity was observed in the families with these RP1 gene mutations. Two
      nondisease-associated polymorphisms were also detected, with the frequency of one
      of these variants being significantly low in Black African individuals.
      CONCLUSIONS: Mutations were only found in Caucasian families with origins in the
      British Isles. The observed RP1 mutation frequency of 5.3% in SA ADRP patients is
      comparable to the frequency reported in other populations.

PMID- 16568032
TI  - Data day.

PMID- 16568031
TI  - Identification of calcium channel alpha1 subunit mRNA expressed in retinal
      bipolar neurons.
AB  - PURPOSE: Glutamate release from goldfish bipolar cell terminals is driven by Ca2+
      influx through L-type calcium channels that exhibit several uncommon features,
      including rapid kinetics of activation and deactivation, slow inactivation, and
      activation at an unusually negative voltage range for L-type channels. The
      purpose of this study was to establish the molecular identities of the alpha1
      subunits responsible for these distinctive properties. METHODS: Transcripts for
      calcium channel alpha1 subunits expressed in individual goldfish ON-type bipolar
      cells were identified using single-cell reverse transcriptase polymerase chain
      reaction (RT-PCR). After cloning the goldfish homologs of the zebrafish and
      mammalian subunits, we designed sets of nested primers that are specific for
      Cav1.3a, and Cav1.3b L-type calcium channels. RESULTS: Large-terminal, ON-type
      bipolar cells express transcripts of Cav1.3a and/or Cav1.3b. CONCLUSIONS: The
      endogenous expression of only one or both subunits in a single cell raises the
      possibility of functionally distinct classes of bipolar cells that differ in
      calcium current properties.

PMID- 16568034
TI  - Misinformation.

PMID- 16568035
TI  - Anecdotal data.

PMID- 16568036
TI  - RITA outcomes.

PMID- 16568037
TI  - Territorial disputes.

PMID- 16568038
TI  - Ethical dilemma.

PMID- 16568039
TI  - A longstanding problem.

PMID- 16568040
TI  - Rose-tinted academia.

PMID- 16568041
TI  - Awarding degrees.

PMID- 16568042
TI  - Missing the point.

PMID- 16568052
TI  - Oldest recorded case of impacted wisdom teeth.

PMID- 16568054
TI  - The dentinal caries experience of children in the United Kingdom, 2003.
AB  - BACKGROUND: The 2003 Children's Dental Health Survey is the fourth in a series of
      decennial national children's dental health surveys. AIMS: This paper reports the
      survey-derived estimates of dentinal caries experience of children aged five,
      eight, 12 and 15 years, considering the trends over recent decades and the
      position in 2003 following changes in disease presentation and the use of
      additional criteria. METHODOLOGY: A representative UK sample of children in the
      four specified age groups were invited to participate in a clinical dental
      examination in school. A total of 12,698 children were sampled and 10,381 were
      examined (82%). Examinations were undertaken in school by trained and calibrated
      examining teams using reclining chairs and portable lights, the criteria were
      visual, limited to dentine caries and no diagnostic aids were employed. In order
      to compare trend data with 1993 and earlier surveys the criteria allowed the re
      classification of the full 2003a results (those including cavities and visual
      dentine caries - D(3cv)MFT/d(3cv)mft) according to the previous criteria to
      produce results labelled 2003b (those restricted to dentinal cavities-
      D(3c)MFT/d(3c)mft). RESULTS AND CONCLUSIONS: The experience of obvious dentinal
      caries in children within the UK has continued to change over the last decade and
      patterns are different for the two dentitions. While continuing overall
      improvements are evident for permanent teeth across the UK (D(3c) for 15-year-old
      children falling from 42% in 1983, via 30% in 1993 to 13% in 2003 for example),
      trends amongst those experiencing dentinal caries are more concerning and there
      have been no statistically significant improvements for primary teeth (the mean
      number of teeth with obvious dentine decay (d(3c)) at age five years being 1.3 in
      1983 and 1.4 in both 1993 and 2003). The inclusion in the criteria of visual
      dentinal caries resulted in higher estimates of mean caries and mean caries
      experience in the permanent dentition (at age 15 years D(3) increasing from 0.2
      to 0.8, D(3)MFT increasing from 1.6 to 2.0 for example) but not the primary
      dentition (where the estimates for % d(3)mft at age five years were identical at
      43%). Geographic variations also persist across the UK (% with D(3cv)MFT at 12
      years being 41% for England, 54% Wales, 73% Northern Ireland and 43% for the UK;
      % with d(3cv)mft at age 5 years: 41% for England, 52% Wales, 61% Northern Ireland
      and 43% for the UK). These survey results have implications for planning and for
      daily practice, but must be interpreted carefully acknowledging the specific
      survey conditions and diagnostic criteria employed.

PMID- 16568055
TI  - Primary tuberculosis of the tongue: a rare nodular presentation.
AB  - We report a case of a 38-year-old male who presented to us with a nodular
      swelling of the tongue with cervical lymphadenopathy suggestive of a malignancy.
      The lesion was diagnosed to be of tuberculous origin and the patient responded
      well to anti-tubercular chemotherapy.

PMID- 16568062
TI  - The behaviour, social status and number of teeth extracted in children under
      general anaesthesia: a referral centre revisited.
AB  - OBJECTIVE: To report on the changing profile of children attending for Dental
      General Anaesthetic extractions (DGA) at the same centre in 1998 and again in
      2004 compared to 1991. DESIGN: Prospective clinical. SETTING: Glasgow Dental
      Hospital DGA service during August 1999 and August/September 2004. SUBJECTS AND
      METHOD: Children presenting for DGA extractions. Data recorded: age, gender,
      number of teeth extracted and level of behaviour using the Frankl scale. RESULTS:
      In 1999: 190 children (97 boys) mean age five years. In 2004: 106 children (55
      boys) mean age five years. There was a significant increase in the mean number of
      teeth extracted (p < 0.001), 4.2 (1-16) and 7.8 (1-17) in 1999 and 2004
      respectively, compared to 3.7 in 1991. Twenty-six per cent of children had
      between six and 16 teeth extracted in 1999 compared to 74% in 2004. Significantly
      fewer children demonstrated "definitely positive" behaviour compared to 1991.
      Children were in the poorest socioeconomic groups, reflecting the geographic
      area. CONCLUSION: Over half of the children were aged five years and under. Fewer
      highly co-operative children were treated. More teeth were extracted per child,
      suggesting that there should be greater opportunities to carry out restorations,
      not just extractions under general anaesthesia.

PMID- 16568076
TI  - Star of India. The First MClinDent (prosthodontics) Residential Week in India,
      February 4-10, 2006.

PMID- 16568063
TI  - Microbiological evaluation of photo-activated disinfection in endodontics (an in
      vivo study).
AB  - OBJECTIVE: To determine the microbiological effect of photoactivated disinfection
      (PAD) as an adjunct to normal root canal disinfection in vivo. DESIGN: A
      randomised trial carried out in general dental practice. SUBJECTS AND METHODS:
      Patients presenting with symptoms of irreversible pulpitis or periradicular
      periodontitis requiring endodontic therapy were selected at random. A
      microbiological sample of the canal was taken on accessing the canal, after
      conventional endodontic therapy, and finally after the PAD process
      (photosensitiser and light) had been carried out on the prepared canal. All three
      samples from each canal were plated within 30 minutes of sampling and cultured
      anaerobically for five days. Growth of viable bacteria was recorded for each
      sample to determine bacterial load. RESULTS: Thirty of the 32 canals were
      included in the results. Cultures from the remaining two did not reach the
      laboratory within the target time during which viability was sustained. Of the
      remaining 30, 10 canals were negative to culture. These were either one of the
      canals in multi rooted teeth where the others were infected or where a pre
      treatment with a poly-antibiotic paste had been applied to hyperaemic vital
      tissue. Sixteen of the remainder were negative to culture after conventional
      endodontic therapy. Three of the four which had remained infected cultured
      negative after the PAD process. In the one canal where culturable bacteria were
      still present, a review of the light delivery system showed a fracture in the
      fibre reducing the effective light output by 90%. CONCLUSIONS: The PAD system
      offers a means of destroying bacteria remaining after using conventional
      irrigants in endodontic therapy.

PMID- 16568078
TI  - Overexpression of antizyme-inhibitor in NIH3T3 fibroblasts provides growth
      advantage through neutralization of antizyme functions.
AB  - Antizyme inhibitor (AzI) is a homolog of ornithine decarboxylase (ODC), a key
      enzyme of polyamine synthesis. Antizyme inhibitor retains no enzymatic activity,
      but exhibits high affinity to antizyme (Az), a negative regulator of polyamine
      homeostasis. As polyamines are involved in maintaining cellular proliferation,
      and since AzI may negate Az functions, we have investigated the role of AzI in
      regulating cell growth. We show here that overexpression of AzI in NIH3T3 cells
      increased growth rate, enabled growth in low serum, and permitted anchorage
      independent growth in soft agar, while reduction of AzI levels by AzI siRNA
      reduced cellular proliferation. Moreover, AzI overproducing cells gave rise to
      tumors when injected into nude mice. AzI overexpression resulted in elevation of
      ODC activity and of polyamine uptake. These effects of AzI are a result of its
      ability to neutralize Az, as overexpression of an AzI mutant with reduced Az
      binding failed to alter cellular polyamine metabolism and growth properties. We
      also demonstrate upregulation of AzI in Ras transformed cells, suggesting its
      relevance to some naturally occurring transformations. Finally, increased uptake
      activity rendered AzI overproducing and Ras-transformed cells more sensitive to
      toxic polyamine analogs. Our results therefore imply that AzI has a central and
      meaningful role in modulation of polyamine homeostasis, and in regulating
      cellular proliferation and transformation properties.

PMID- 16568079
TI  - Expression of Snail protein in tumor-stroma interface.
AB  - The product of Snail gene is a repressor of E-cadherin transcription and an
      inductor of the epithelial-to-mesenchymal transition in several epithelial tumor
      cell lines. In order to examine Snail expression in animal and human tissues, we
      have raised a monoclonal antibody (MAb) that reacts with the regulatory domain of
      this protein. Analysis of murine embryos shows that Snail is expressed in
      extraembryonic tissues and embryonic mesoderm, in mesenchymal cells of lungs and
      dermis as well as in cartilage. Little reactivity was detected in adult tissues
      as Snail was not constitutively expressed in most mesenchymal cells. However,
      Snail expression was observed in activated fibroblasts involved in wound healing
      in mice skin. Moreover, Snail was detected in pathological conditions causing
      hyperstimulation of fibroblasts, such as fibromatosis. Analysis of Snail
      expression in tumors revealed that it was highly expressed in sarcomas and
      fibrosarcomas. In epithelial tumors, it presented a more limited distribution,
      restricted to stromal cells placed in the vicinity of the tumor and to tumoral
      cells in the same areas. These results demonstrate that Snail is present in
      activated mesenchymal cells, indicate its relevance in the communication between
      tumor and stroma and suggest that it can promote the conversion of carcinoma
      cells to stromal cells.

PMID- 16568080
TI  - TIPUH1 encodes a novel KRAB zinc-finger protein highly expressed in human
      hepatocellular carcinomas.
AB  - To achieve a better understanding of mechanisms that underlie
      hepatocarcinogenesis and to identify novel target molecules for diagnosis and
      therapy of hepatocellular carcinoma (HCC), we previously analysed gene-expression
      profiles of 20 HCC tissues on a cDNA microarray. Among the genes upregulated in
      the tumor tissues compared with their nontumor counterparts, we focused on a
      novel gene termed transcription-involved protein upregulated in HCC (TIPUH1) that
      putatively encoded a 500-amino-acid protein containing 12 zinc-finger domains and
      a Kruppel-associated box domain. Multiple-tissue northern blot analysis revealed
      it's testis- and placenta-specific expression in normal tissues. Colony-formation
      assay in soft agar showed that TIPUH1 conferred anchorage-independent growth to
      NIH3T3 cells, suggesting its oncogenic activity. Conversely, specific siRNA for
      TIPUH1 knocked down its expression in HCC cells, which resulted in their growth
      inhibition. We identified four TIPUH1-interacting proteins including TIF1beta, a
      transcription-intermediary protein, and three involved in pre-mRNA processing
      (hnRNPU, hnRNPF, and Nucleolin), suggesting that overexpressed TIPUH1 may play a
      role in hepatocarcinogenesis by regulating transcription and/or RNA processing of
      growth control genes. These data may contribute to a better understanding of
      liver neoplasia, and to the development of novel strategy for treatment of HCCs.

PMID- 16568081
TI  - Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in
      neuroblastoma.
AB  - Retinoic acid (RA) has been shown to induce neuronal differentiation and/or
      apoptosis, and is widely used as a chemotherapeutic agent for treating the
      patients with neuroblastoma. However, the therapeutic effect of RA is still
      limited. To unveil the molecular mechanism(s) inducing differentiation and
      apoptosis in neuroblastoma cells, we compared CHP134 and NB-39-nu cell lines, in
      which all-trans-RA (ATRA) induces apoptosis, with LA-N-5 and RTBM1 cell lines, in
      which it induces neuronal differentiation. Here, we found that Bcl-2 was strongly
      downregulated in CHP134 and NB-39-nu cells, whereas it was abundantly expressed
      in LA-N-5 and RTBM1 cells. ATRA-mediated apoptosis in CHP134 and NB-39-nu cells
      was associated with a significant activation of caspase-9 and caspase-3 as well
      as cytoplasmic release of cytochrome c from mitochondria in a p53-independent
      manner. Enforced expression of Bcl-2 significantly inhibited ATRA-mediated
      apoptosis in CHP134 cells. In addition, treatment of RTBM1 cells with a Bcl-2
      inhibitor, HA14-1, enhanced apoptotic response induced by ATRA. Of note, two out
      of 10 sporadic neuroblastomas expressed bcl-2 at undetectable levels and
      underwent cell death in response to ATRA in primary cultures. Thus, our present
      results suggest that overexpression of Bcl-2 is one of the key mechanisms to give
      neuroblastoma cells the resistance against ATRA-mediated apoptosis. This may
      provide a new therapeutic strategy against the ATRA-resistant and aggressive
      neuroblastomas by combining treatment with ATRA and a Bcl-2 inhibitor.

PMID- 16568082
TI  - CEA-related cell adhesion molecule-1 is involved in angiogenic switch in prostate
      cancer.
AB  - We demonstrate here that epithelial carcinoembryonic antigen (CEA)-related cell
      adhesion molecule-1 (CEACAM1) downregulation in prostate intraepithelial
      neoplasia (PIN) is inversely correlated with its upregulation in adjacent blood
      vessels. CEACAM1 silencing in prostate cancer cell line DU-145 via small
      interfering ribonucleic acid (siRNA) increased but its overexpression suppressed
      the expression of angiogenic/lymphangiogenic factors such as vascular endothelial
      growth factor (VEGF)-A, -C and -D, and angiogenic inhibitor collagen
      18/endostatin. Furthermore, CEACAM1 overexpression in DU-145 cells increased but
      CEACAM1 silencing reduced angiopoietin-1 expression. Inverse relation was found
      for angiopoietin-2. Supernatant of CEACAM1-overexpressing DU-145 suppressed but
      that of CEACAM1-silenced increased the VEGF-induced endothelial tubes. Electron
      microscopically the majority of PIN-associated blood vessels was structurally
      destabilized exhibiting endothelial fenestration, trans- and inter-endothelial
      gaps. In some PIN areas, invasion of single tumor cells into the destabilized
      blood vessels was observed. These data show that disappearance of epithelial
      CEACAM1 in PIN is accompanied by its upregulation in adjacent vasculature which
      apparently correlates with vascular destabilization and increased vascularization
      of prostate cancer. Strategies to either conserve the epithelial CEACAM1 or to
      target endothelial CEACAM1 might be useful for an anti-angiogenic therapy of
      prostate cancer.

PMID- 16568083
TI  - Regulation of vimentin by SIP1 in human epithelial breast tumor cells.
AB  - The expression of Smad interacting protein-1 (SIP1; ZEB2) and the de novo
      expression of vimentin are frequently involved in epithelial-to-mesenchymal
      transitions (EMTs) under both normal and pathological conditions. In the present
      study, we investigated the potential role of SIP1 in the regulation of vimentin
      during the EMT associated with breast tumor cell migration and invasion.
      Examining several breast tumor cell lines displaying various degrees of
      invasiveness, we found SIP1 and vimentin expression only in invasive cell lines.
      Also, using a model of cell migration with human mammary MCF10A cells, we showed
      that SIP1 is induced specifically in vimentin-positive migratory cells.
      Furthermore, transfection of SIP1 cDNA in MCF10A cells increased their vimentin
      expression both at the mRNA and protein levels and enhanced their migratory
      abilities in Boyden Chamber assays. Inversely, inhibition of SIP1 expression by
      RNAi strategies in BT-549 cells and MCF10A cells decreased vimentin expression.
      We also showed that SIP1 transfection did not activate the TOP-FLASH reporter
      system, suggesting that the beta-catenin/TCF pathway is not implicated in the
      regulation of vimentin by SIP1. Our results therefore implicate SIP1 in the
      regulation of vimentin observed in the EMT associated with breast tumor cell
      migration, a pathway that may contribute to the metastatic progression of breast
      cancer.

PMID- 16568084
TI  - The SRC family kinase LYN redirects B cell receptor signaling in human SLP65
      deficient B cell lymphoma cells.
AB  - SLP65 represents a critical component in (pre-) B cell receptor signal
      transduction but is compromised in a subset of pre-B cell-derived acute
      lymphoblastic leukemia. Based on these findings, we investigated (i.) whether
      SLP65-deficiency also occurs in mature B cell-derived lymphoma and (ii.) whether
      SLP65-deficient B cell lymphoma cells use an alternative B cell receptor
      signaling pathway in the absence of SLP65. Indeed, expression of SLP65 protein
      was also missing in a fraction of B cell lymphoma cases. While SLP65 is essential
      for B cell receptor-induced Ca2+ mobilization in normal B cells, B cell receptor
      engagement in SLP65-deficient as compared to SLP65-reconstituted B cell lymphoma
      cells resulted in an accelerated yet shortlived Ca2+-signal. B cell receptor
      engagement of SLP65-deficient lymphoma cells involves SRC kinase activation,
      which is critical for B cell receptor-dependent Ca2+-mobilisation in the absence
      but not in the presence of SLP65. As shown by RNA interference, the SRC kinase
      LYN is required for B cell receptor-induced Ca2+ release in SLP65-deficient B
      cell lymphoma cells but dispensable after SLP65-reconstitution. B cell receptor
      engagement in SLP65-deficient B cell lymphoma cells also resulted in tyrosine
      phosphorylation of the proliferation- and survival-related MAPK1 and STAT5
      molecules, which was sensitive to silencing of the SRC kinase LYN. Inhibition of
      SRC kinase activity resulted in growth arrest and cell death specifically in
      SLP65-deficient lymphoma cells. These findings indicate that LYN can short
      circuit conventional B cell receptor signaling in SLP65-deficient B cell lymphoma
      cells and thereby promote activation of survival and proliferation-related
      molecules.

PMID- 16568085
TI  - Expression of Dickkopf genes is strongly reduced in malignant melanoma.
AB  - The Dickkopf (DKK) genes were originally identified as factors inducing head
      formation in Xenopus. The genes code for inhibitors that are involved in Wnt
      signaling. We speculate that loss of DKK expression plays a role in development
      or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and
      tissue samples of malignant melanoma for loss of DKK, especially DKK-3
      transcription. We found that DKK-1, -2 and -3 were downregulated or lost in all
      cell lines and in most of the tumor samples analysed. Reduced DKK-3 expression
      occurred as early as in primary tumors detected by both immunohistochemical and
      reverse transcription-polymerase chain reaction RT-PCR analysis. Functional
      assays with stable DKK-3 transfected cell lines revealed that DKK-3 expression
      increased cell-cell adhesion and decreased cell migration. Further,
      downregulation of fibronectin, snail-1 and re-expression of E-cadherin was found
      in the DKK-3 expressing cell clones supporting a role of DKK-3 in tumor
      progression. Our studies thus indicate that loss of DKK-3 expression may
      contribute to melanoma progression.

PMID- 16568086
TI  - MEKK1 controls matrix degradation and tumor cell dissemination during metastasis
      of polyoma middle-T driven mammary cancer.
AB  - Mammary tumor cells are required to degrade the surrounding matrix and
      disseminate in order to metastasize, and both of these processes are controlled
      by a tumor cell-signaling network that remains poorly defined. MEKK1 is a MAPKKK
      that regulates both the extracellular signal regulated kinase (ERK1/2) and the c
      Jun amino terminal kinase (JNK) signaling pathways. MEKK1 signaling regulates
      migration through control of cell adhesion and is required for inducible
      expression of urokinase-type plasminogen activator (uPA). MEKK1-deficient mice
      with mammary gland-targeted expression of the polyoma middle T antigen (PyMT)
      transgene develop primary mammary tumors at a rate and frequency similar to wild
      type littermates, indicating that MEKK1 deficiency does not affect PyMT-mediated
      transformation. However, MEKK1-/- mice display significantly delayed tumor cell
      dissemination and lung metastasis. Delayed MEKK1-dependent tumor dissemination is
      associated with markedly reduced tumor uPA expression, gelatinase activity, and
      prolonged tumor basement membrane integrity. siRNA-mediated MEKK1 knockdown
      inhibits uPA activity, cell migration and invasion in MDA-MB-231 human breast
      cancer cells. Thus MEKK1 controls tumor progression by regulating both the
      migration and proteolysis aspects of tumor cell invasiveness. To our knowledge,
      this is the first example of a MAPKKK that regulates metastasis through control
      of tumor invasiveness.

PMID- 16568087
TI  - The Mcs7 quantitative trait locus is associated with an increased susceptibility
      to mammary cancer in congenic rats and an allele-specific imbalance.
AB  - Identification of high-penetrance breast cancer genes such as Brca1 has been
      accomplished by analysing familial cases. However, these genes occur at low
      frequency and do not account for the majority of genetic risk. Identification of
      low-penetrance alleles that occur commonly in populations may benefit from
      unbiased genome-wide screening. One such approach uses linkage studies in rodent
      models to identify homologous human candidates. The Wistar Kyoto (WKy) rat is
      resistant to mammary carcinomas induced with 7,12-dimethybenz[a]anthracene
      (DMBA), whereas the Wistar Furth (WF) strain is susceptible. Previous genome-wide
      linkage studies in crosses of these strains identified three WKy resistance
      quantitative trait loci, Mcs5, Mcs6 and Mcs8, and one predicted to increase
      susceptibility, Mcs7. The Mcs7 region on rat chromosome 10 (RNO10) is orthologous
      to human 17q, a common site of genetic aberrations in breast cancer. Here, we
      establish the independent phenotype conferred by Mcs7 using congenic rats
      carrying the WKy Mcs7 locus on a WF background. Tumor multiplicity was
      significantly higher ( approximately 50%) in DMBA-treated congenics homozygous
      and heterozygous for the WKy allele at the Mcs7 locus, compared to controls. We
      also investigated allelic imbalance (AI) in mammary carcinomas from (WKy x WF)F1
      rats and Mcs7 heterozygous congenics. Of the four known WKy Mcs loci tested, only
      Mcs7 displayed AI. The pattern of AI in carcinomas from both F1 and Mcs7 congenic
      rats was similar, suggesting a WF allelic loss. Together, these data suggest that
      one or more breast cancer-related genes are located within the dominantly acting
      WKy allele at the Mcs7 locus.

PMID- 16568089
TI  - SUMO modification of Sam68 enhances its ability to repress cyclin D1 expression
      and inhibits its ability to induce apoptosis.
AB  - Sam68 (Src associated in mitosis; 68 kDa) is an RNA-binding protein and substrate
      of Src family kinases. It is thought to play a role in cell cycle progression.
      Overexpression of Sam68 in fibroblasts was reported to have two separable
      functions dependent on its ability to bind RNA--cell cycle arrest or the
      induction of apoptosis. Post-translational modification with SUMO (small
      ubiquitin-like modifier) is common to many transcription factors and can regulate
      protein localization, stability and function. Here we show Sam68 to be modified
      by SUMO, and demonstrate that the SUMO E3 ligase (PIAS1) (protein inhibitor of
      activated STAT1) can enhance Sam68 sumoylation. Lysine 96, the first lysine in
      the amino-terminal region of Sam68, was found to be the major SUMO acceptor site.
      Mutation of the SUMO acceptor lysine to arginine enhanced the ability of Sam68 to
      induce apoptosis but inhibited its ability to act as a transcriptional inhibitor
      of cyclin D1 expression. A SUMO-1 Sam68 fusion protein, on the other hand,
      inhibited the ability of Sam68 to induce apoptosis but was a strong repressor of
      cyclin D1 expression. Thus, SUMO may be an important regulator of Sam68 function
      in cell cycle progression.

PMID- 16568088
TI  - Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes
      colonic carcinoma metastasis.
AB  - Cellular metastasis is the most detrimental step in carcinoma disease
      progression, yet the mechanisms that regulate this process are poorly understood.
      CXCL12 and its receptor CXCR4 are co-expressed in several tissues and cell types
      throughout the body and play essential roles in development. Disruption of either
      gene causes embryonic lethality due to similar defects. Post-natally, CXCL12
      signaling has a wide range of effects on CXCR4-expressing cells, including the
      directed migration of leukocytes, lymphocytes and hematopoietic stem cells.
      Recently, this signaling axis has also been described as an important regulator
      of directed carcinoma cell metastasis. We show herein that while CXCR4 expression
      remains consistent, constitutive colonic epithelial expression of CXCL12 is
      silenced by DNA hypermethylation in primary colorectal carcinomas as well as
      colorectal carcinoma-derived cell lines. Inhibition of DNA methyltransferase
      (Dnmt) enzymes with 5-aza-2'-deoxycytidine or genetic ablation of both Dnmt1 and
      Dnmt3b prevented promoter methylation and restored CXCL12 expression. Re
      expression of functional, endogenous CXCL12 in colorectal carcinoma cells
      dramatically reduced metastatic tumor formation in mice, as well as foci
      formation in soft agar. Decreased metastasis was correlated with increased
      caspase activity in cells re-expressing CXCL12. These data constitute the unique
      observation that silencing CXCL12 within colonic carcinoma cells greatly enhances
      their metastatic potential.

PMID- 16568090
TI  - Oncogenic HRAS suppresses clusterin expression through promoter hypermethylation.
AB  - Silencing of gene expression by methylation of CpG islands in regulatory elements
      is frequently observed in cancer. However, an influence of the most common
      oncogenic signalling pathways onto DNA methylation has not yet been investigated
      thoroughly. To address this issue, we identified genes suppressed in HRAS
      transformed rat fibroblasts but upregulated after treatment with the
      demethylating agent 5-Aza-2-deoxycytidine and with the MEK1,2 inhibitor U0126.
      Analysis of gene expression by microarray and Northern blot analysis revealed the
      MEK/ERK target genes clusterin, matrix metalloproteinase 2 (Mmp2), peptidylpropyl
      isomerase C-associated protein, syndecan 4, Timp2 and Thbs1 to be repressed in
      the HRAS-transformed FE-8 cells in a MEK/ERK- and methylation-dependent manner.
      Hypermethylation of putative regulatory elements in HRAS-transformed cells as
      compared to immortalized fibroblasts was detected within a CpG island 14.5 kb
      upstream of clusterin, within the clusterin promoter and within a CpG island of
      the Mmp2 promoter by bisulphite sequencing. Furthermore, hypermethylation of the
      clusterin promoter was observed 10 days after induction of HRAS in immortalized
      rat fibroblasts and a clear correlation between reduced clusterin expression and
      hypermethlyation could also be observed in distinct rat tissues. These results
      suggest that silencing of individual genes by DNA methylation is controlled by
      oncogenic signalling pathways, yet the mechanisms responsible for initial target
      gene suppression are variable.

PMID- 16568091
TI  - Identification of STAT3 as a specific substrate of breast tumor kinase.
AB  - Breast tumor kinase (Brk) is a non-receptor tyrosine kinase distantly related to
      the Src family kinase. It is expressed in more than 60% of breast tumors, but the
      biological role of this kinase remains to be determined. Only a limited number of
      substates have been identified for Brk, and the link of Brk to tumorigenesis
      remains largely unknown. In this study, we provide evidence that the signal
      transducer and activator of transcription 3, STAT3, is a physiological target of
      Brk. Activation of STAT3 previously has been linked to oncogenesis, and results
      in this study demonstrate that STAT3 is tyrosine phosphorylated and
      transcriptionally activated in cells expressing endogenous Brk. Signal transducer
      and activator of transcription 3 is specifically targeted since other STAT
      members are not responsive to Brk expression. Signal transducer and activator of
      transcription 3 activation requires the catalytic activity of Brk, and expression
      of both STAT3 and Brk stimulate cellular proliferation. In addition, we have
      identified a negative regulator of Brk, the suppressor of cytokine signaling,
      SOCS3. The SOCS3 protein is known to block signaling mediated by cytokine
      receptors, and here we find that SOCS3 is able to repress the activity of the Brk
      non-receptor tyrosine kinase.

PMID- 16568092
TI  - Members of the hSWI/SNF chromatin remodeling complex associate with and are
      phosphorylated by protein kinase B/Akt.
AB  - In an adenosine triphosphate (ATP)-dependent process, the hSWI/SNF chromatin
      remodeling complex functions to alter chromatin structure, thereby regulating
      transcription factor access to DNA. In addition to interactions with
      transcription factors and recognition of acetylated histone residues, the
      chromatin remodeling activity of hSWI/SNF has also been shown to respond to a
      variety of cell signaling pathways. Our results demonstrate a novel interaction
      between the serine/threonine kinase Akt and members of the hSWI/SNF chromatin
      remodeling complex. Activation of Akt in HeLa cells resulted in its association
      with hSWI/SNF subunits: INI1, BAF155 and BAF170, as well as actin. BAF155 became
      preferentially recognized by an antibody that detects phosphorylated Akt
      substrates upon activation of Akt, suggesting that BAF155 may be an in vivo
      target for phosphorylation by Akt. Glutathione-S-transferase (GST) pulldown
      experiments demonstrated that INI1 and BAF155 were both capable of directly
      interacting with Akt. Finally, in vitro kinase assays provided additional
      evidence that BAF155 and potentially INI1 are substrates for Akt phosphorylation.
      These data provide the first evidence that Akt signaling may modulate function of
      the hSWI/SNF complex.

PMID- 16568093
TI  - BH3 peptidomimetics potently activate apoptosis and demonstrate single agent
      efficacy in neuroblastoma.
AB  - The major impediment to cure for many malignancies is the development of therapy
      resistance with resultant tumor progression. Genetic alterations leading to
      subversion of inherent apoptosis pathways are common themes in therapy
      resistance. Bcl-2 family proteins play a critical role in regulating
      mitochondrial apoptosis that governs chemotherapeutic effects, and defective
      engagement of these pathways contributes to treatment failure. We have studied
      the efficacy of BH3 peptidomimetics consisting of the minimal death, or BH3,
      domains of the proapoptotic BH3-only proteins Bid and Bad to induce apoptosis
      using neuroblastoma (NB) as a model system. We demonstrate that BH3 peptides,
      modified with an arginine homopolymer for membrane transduction (called r8-BidBH3
      and r8-BadBH3, respectively), potently induce apoptosis in NB cells, including
      those with MYCN amplification. Cell death is caspase 9 dependent, consistent with
      a requirement for the intrinsic mitochondrial pathway. Substitutions at highly
      conserved residues within the r8-BidBH3 peptide abolish apoptotic efficacy
      supporting activity through specific BH domain interactions. Concomitant exposure
      to r8-BadBH3 and r8-BidBH3 at sublethal monotherapy doses revealed potent synergy
      consistent with a competitive displacement model, whereby BH3 peptides displace
      sequestered BH3 proteins to induce cell death. Further, BH3 peptides demonstrate
      antitumor efficacy in a xenograft model of NB in the absence of additional
      genotoxic or trophic stressors. These data provide proof of principle that
      targeted re-engagement of apoptosis pathways may be of therapeutic utility, and
      BH3-like compounds are attractive lead agents to re-establish therapy-induced
      apoptosis in refractory malignancies.

PMID- 16568094
TI  - MAP1D, a novel methionine aminopeptidase family member is overexpressed in colon
      cancer.
AB  - N-terminal methionine removal is an important cellular process required for
      proper biological activity, subcellular localization, and eventual degradation of
      many proteins. The enzymes that catalyze this reaction are called Methionine
      Aminopeptidases (MAPs). To date, only two MAP family members, MAP1A and MAP2,
      have been well characterized and studied in mammals. In our studies, we have
      cloned a full length MAP1D gene. Expression and purification of full length
      recombinant protein shows that the sequence encodes an enzyme with MAP activity.
      MAP1D is overexpressed in colon cancer cell lines and in colon tumors as compared
      to matched normal tissue samples. Downregulation of MAP1D expression by shRNA in
      HCT-116 colon carcinoma cells reduces anchorage-independant growth in soft agar.
      These data suggest that MAP1D is a potentially oncogenic, novel member of the MAP
      gene family that may play an important role in colon tumorigenesis.

PMID- 16568095
TI  - Achaete-scute like 2 (ascl2) is a target of Wnt signalling and is upregulated in
      intestinal neoplasia.
AB  - Achaete-scute like (ASCL)2 is a basic helix-loop-helix transcription factor
      essential for the maintenance of proliferating trophoblasts during placental
      development. Using oligonucleotide microarrays we identified ascl2 as a gene
      significantly upregulated in colorectal adenocarcinomas (n=36 cancers, n=16
      normals; 15-fold, P<0.0001). This finding was confirmed by quantitative reverse
      transcriptase (RT)-PCR on large intestinal cancers (n=29 cancers, n=16 normals;
      10-fold, P<0.0001). In situ hybridization for ascl2 demonstrated expression at
      the base of small and large intestinal crypts (n=304), but in no other normal
      tissues excepting placenta. By in situ hybridization, 52-71% of colorectal
      adenomas (n=187), 50-73% of large (n=327) and 33-64% of small intestinal
      adenocarcinomas (n=124) were positive for ascl2 expression. Upregulation of
      murine ascl2 was also observed using oligonucleotide microarrays, quantitative RT
      PCR and in situ hybridization on apcmin/+ and apc1638N/+ smad4-/+ tumours. Tumour
      cell lines stably transfected with LEF1(DN) or APC2, or transiently transfected
      with short-interfering RNA (siRNA) against beta-catenin showed a significant
      downregulation of ascl2. Colocalization of ascl2 with nuclear beta-catenin was
      observed in 73 small intestinal adenocarcinomas (P=0.0008) and apcmin/+ tumours.
      Preliminary in vitro data suggest ascl2 may promote progression through the G2/M
      cell cycle checkpoint. In summary, ascl2 is a putative regulator of proliferation
      that is overexpressed in intestinal neoplasia.

PMID- 16568097
TI  - Putting the brain back together.

PMID- 16568096
TI  - Involvement of the Rho/Rac family member RhoG in caveolar endocytosis.
AB  - We show here that the GTPase RhoG is involved in caveolar trafficking. Wild-type
      RhoG moves sequentially to the plasma membrane, intracellular vesicles, and the
      Golgi apparatus along markers of this endocytic pathway. Such translocation is
      associated with changes in RhoG GDP/GTP levels and is highly dependent on lipid
      raft integrity and on the function of the GTPase dynamin2. In addition, the
      constitutively active RhoG(Q61L) mutant is preferentially located in endocytic
      vesicles that can be decorated with markers of the caveola-derived endocytic
      pathway. RhoG(Q61L), but not the analogous Rac1 mutant protein, affects caveola
      internalization and the subsequent delivery of endocytic vesicles to the Golgi
      apparatus. The expression of RhoG/Rac1 chimeric proteins and RhoG(Q61L) effector
      mutants in cells induces alterations in the internalization of caveolae and
      severe changes in vesicle structure, respectively. However, the knockdown of
      endogenous rhoG transcripts using small interfering RNAs does not affect
      significantly the trafficking of caveola-derived vesicles, suggesting that RhoG
      function is dispensable for this endocytic process or, alternatively, that its
      function is compensated by other molecules. Taken together, these observations
      assign a novel function to RhoG and suggest that caveolar trafficking, as
      previously shown for other endocytic routes, is modulated by GTPases of the Ras
      superfamily.

PMID- 16568098
TI  - Purkinje cells in awake behaving animals operate at the upstate membrane
      potential.

PMID- 16568101
TI  - Even chromatin gets the blues.

PMID- 16568103
TI  - Measuring the brain's assumptions.

PMID- 16568102
TI  - A mint of mutations in TRPM8 leads to cool results.

PMID- 16568104
TI  - Go with the flow: signaling from the ventricle directs neuroblast migration.

PMID- 16568105
TI  - Rational rats.

PMID- 16568106
TI  - Going down BOLDly.

PMID- 16568107
TI  - hPepT1 mediates bacterial tripeptide fMLP uptake in human monocytes.
AB  - Here, we examined hPepT1 expression in the monocytic cell line, KG-1. Reverse
      transcription polymerase chain reaction (RT-PCR) analysis revealed that hPepT1 is
      expressed in KG-1 cells, while cDNA cloning and direct sequencing confirmed the
      sequence of KG-1 hPepT1 (accession number, AY634368). Immunoblotting of cell
      lysates from KG-1 cells or macrophages isolated from human peripheral blood
      revealed a approximately 100 kDa immunoreactive band mainly present in the
      membrane fraction. Uptake experiments showed that the transport of 20 microM
      radiolabeled Gly-Sarcosine ([14C]Gly-Sar) in KG-1 cells was Na+, Cl- dependent
      and disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS)-sensitive. In
      addition, hPepT1 activity was likely to be coupled to a Na+/H+ exchanger, as
      evidenced by the fact that [14C]Gly-Sar uptake was not affected by the absence of
      Na+ when cells were incubated at low pH (5.2). Interestingly, hPepT1-mediated
      transport was reduced in KG-1 cells incubated at low pH as it was also observed
      in nonpolarized Caco2-BBE cells. This pattern of pH-dependence is due to a
      disruption of the driving force of hPepT1-mediated transport events. This was
      supported by our finding that nonpolarized cells, Caco2-BBE cells and KG-1 cells,
      have an increased permeability to H+ when compared to polarized Caco2-BBE cells.
      Finally, we showed that hPepT1 is responsible for transporting fMLP into
      undifferentiated and differentiated (macrophage-like) KG-1 cells. Together, these
      results show that hPepT1 is expressed in nonpolarized immune cells, such as
      macrophages, where the transporter functions best at the physiological pH 7.2.
      Furthermore, we provide evidence for hPepT1-mediated fMLP transport, which might
      constitute a novel immune cell activation pathway during intestinal inflammation.

PMID- 16568108
TI  - Functional facets of the pulmonary neuroendocrine system.
AB  - Pulmonary neuroendocrine cells (PNECs) have been around for 60 years in the
      scientific literature, although phylogenetically they are ancient. Their
      traditionally ascribed functions include chemoreception and regulation of lung
      maturation and growth. There is recent evidence that neuroendocrine (NE)
      differentiation in the lung is regulated by genes and pathways that are conserved
      in the development of the nervous system from Drosophila to humans (such as
      achaete-scute homolog-1), or implicated in the carcinogenesis of the nervous or
      NE system (such as the retinoblastoma tumor suppressor gene). In addition,
      complex neural networks are in place to regulate chemosensory and other
      functions. Even solitary PNECs appear to be innervated. For the first time ever,
      we have mouse models for lung NE carcinomas, including the most common and
      virulent small cell lung carcinoma. Moreover, PNECs may be important for
      inflammatory responses, and pivotal for lung stem cell niches. These discoveries
      signify an exciting new era for PNECs and are likely to have therapeutic and
      diagnostic applications.

PMID- 16568109
TI  - Enzyme-based visualization of receptor-ligand binding in tissues.
AB  - New methods of elucidating the ligand-binding activity of receptors could improve
      our understanding of receptor function, key events they control, and their
      presence in normal and pathological states. We describe a method for visualizing
      receptor-ligand binding in cells and tissues that substitutes fluorescein for
      radioactive labels, and detects receptor bound, fluoresceinated ligand with an
      antifluorescein/horseradish peroxidase amplification system. Receptor-bound
      ligand is then visualized by light microscopy against a standard hemotoxylin
      stained background of cell structure. Quantitative versions of the assay provide
      an apparent dissociation constant and number of receptors per cell at saturation
      in cell or tissue specimens. Receptors examined include the folate receptor,
      bombesin peptide-binding receptors, the epidermal growth factor receptor, the
      neuropeptide Y receptor, the asialoglycoprotein receptor, and RGD peptide-binding
      integrins. Using fluoresceinated versions of molecules, we show the method can
      visualize and quantitate receptor-bound ligands in cell culture monolayers and
      animal tissue specimens. Ligand binding to receptors present in tissues was
      visualized in normal and pathological samples of human tissue microarrays. The
      enzyme-amplified detection of receptor-bound fluoresceinated ligand is a simple
      and nonradioactive-based method that provides information on the receptor
      activity in tissue specimens.

PMID- 16568110
TI  - The several faces of clinical trials: from new therapies to failed preventive
      strategies.

PMID- 16568111
TI  - Patent foramen ovale closure to treat migraine headache.

PMID- 16568112
TI  - Patent foramen ovale, migraine and stroke: no reason to intervene.

PMID- 16568122
TI  - Can clopidogrel and aspirin lower mortality in patients with acute myocardial
      infarction?

PMID- 16568123
TI  - Should all stroke patients receive tissue plasminogen activator therapy, despite
      mild or improving symptoms?

PMID- 16568124
TI  - Can patent foramen ovale closure using the Cardia PFO occluder reduce the
      occurrence of thromboembolic events?

PMID- 16568125
TI  - Do elderly patients with non-ST-segment elevation acute coronary syndromes
      benefit from early invasive treatment?

PMID- 16568126
TI  - Does abciximab provide long-term benefit for patients with acute myocardial
      infarction treated with stents?

PMID- 16568128
TI  - Coronary heart disease in women: highlights of the past 2 years--stepping stones,
      milestones and obstructing boulders.
AB  - Emerging data continue to highlight important sex-based differences in coronary
      heart disease (CHD) prevention and diagnostic testing, in the management of acute
      coronary syndromes and in the outcomes of CHD therapies. Evidence-based
      guidelines have been developed that offer specific recommendations for clinicians
      and information for women. These guidelines are buttressed by results that have
      become available from randomized, controlled clinical trials in women, and data
      from CHD registries and clinical trials involving both sexes but including
      adequate numbers of women to enable the reporting of sex-specific results.
      Underuse of guideline-based preventive and therapeutic strategies for women
      probably contributes to their less favorable CHD outcomes. Adherence to
      recommendations offers the promise of improving the heart health of women. In
      this article, I summarize new information to guide the preventive, diagnostic and
      therapeutic management of CHD in women.

PMID- 16568127
TI  - Are drug-eluting stents cost-effective when compared with bare-metal stents in a
      real-world setting?

PMID- 16568129
TI  - Immunosuppression for heart transplantation: where are we now?
AB  - The success of cardiac transplantation is largely attributable to the development
      of effective immunosuppressive regimens. The introduction of calcineurin
      inhibitors was pivotal in reducing the frequency of acute rejection and improving
      early survival. Newer agents, including mycophenolate mofetil (MMF) and
      proliferation-signal inhibitors, have shown promise in further reducing acute
      rejection rates and, notably, reducing the frequency of cardiac allograft
      vasculopathy, which limits long-term graft survival. The introduction of first
      year intravascular ultrasonography results as a surrogate marker for outcome
      after cardiac transplantation has helped assessment of the efficacy of
      immunosuppressive medications. Proliferation-signal inhibitors and MMF were shown
      by this imaging method to reduce cardiac allograft vasculopathy. The combination
      of these drugs, in tandem with the weaning of patients off calcineurin
      inhibitors, has been shown to reverse calcineurin-inhibitor-related nephrotoxic
      effects. A randomized trial that compared three of the more common
      immunosuppressive regimens suggested that tacrolimus and MMF are associated with
      a reduction in the frequency of rejection episodes that require treatment and
      have the fewest adverse effects. Finally, the use of statins has brought added
      benefit to immunosuppressive regimens by improving outcomes after cardiac
      transplantation, reportedly because of an immunomodulatory property. Promising
      newer immunosuppressive agents await clinical trials. This review presents an
      overview of the emerging data on immunosuppressive therapy for cardiac
      transplantation.

PMID- 16568130
TI  - Left ventricular dyssynchrony in patients with heart failure: pathophysiology,
      diagnosis and treatment.
AB  - The number of patients with chronic heart failure is increasing rapidly in the
      Western world. Despite the introduction of new pharmacologic therapies, the
      prognosis of these patients remains poor. Left ventricular (LV) dyssynchrony is a
      frequently observed feature in patients with heart failure, and is recognized as
      an important predictor of poor outcome if left untreated. The presence of LV
      dyssynchrony leads to inefficient LV contraction with a decreased cardiac output.
      Moreover, patients with LV dyssynchrony are at increased risk of adverse cardiac
      events. New therapeutic options targeted at restoring normal mechanical
      synchrony, such as cardiac resynchronization therapy, have been shown to improve
      clinical symptoms and prognosis in patients with heart failure. The beneficial
      effects of cardiac resynchronization therapy are predominantly mediated by this
      treatment's ability to reduce LV dyssynchrony. Given these results, adequate
      identification of LV dyssynchrony in patients with heart failure is of paramount
      importance. Several new imaging techniques are proving useful for diagnosis of LV
      dyssynchrony. In particular, advanced echocardiographic techniques (e.g. tissue
      Doppler imaging) and conductance catheter techniques are two accurate methods for
      quantification of LV dyssynchrony. In this review, we discuss the
      pathophysiology, diagnosis and treatment of LV dyssynchrony in patients with
      heart failure.

PMID- 16568131
TI  - Drug Insight: angiotensin-converting-enzyme inhibitors and atrial fibrillation-
      indications and contraindications.
AB  - Large clinical trials have demonstrated that angiotensin-converting-enzyme (ACE)
      inhibitors are associated with beneficial outcomes in patients with arterial
      hypertension, heart failure, coronary artery disease, or a combination of these
      conditions. Other reports have suggested that ACE inhibitors prevent the
      development or recurrence of atrial fibrillation (AF), a common arrhythmia. In
      the TRACE trial, in patients with reduced left ventricular function after
      myocardial infarction, trandolapril reduced the frequency of AF. In the SOLVD
      trial, a 78% reduction in the frequency of AF after infarction was noted with
      enalapril compared with placebo. Studies in patients with persistent AF
      undergoing cardioversion suggest that ACE inhibitors improve outcomes and prevent
      AF recurrences. The mechanism of AF prevention by ACE inhibitors is unclear, but
      experimental data show prevention or attenuation of pacing-induced atrial
      remodeling with ACE inhibitor use. ACE inhibitors decrease angiotensin II
      concentration; angiotension II stimulates mitogen-activated protein kinases,
      which in turn activate fibrosis formation and lead to conduction heterogeneity
      and induction of AF. On the other hand, AF induces atrial dilatation, atrial
      stretch and atrial secretion of ACE. Among other properties, ACE inhibitors have
      a sympatholytic effect and increase baroreceptor sensitivity. This review
      discusses the current data on the use of ACE inhibitors for AF prevention.
      Although these drugs represent a promising therapeutic option for AF patients,
      the data so far seem only supportive rather than definitive. Prospective trials
      are required to validate the benefit of ACE inhibitors and to investigate which
      patients are most likely to benefit from this pharmacological therapy.

PMID- 16568132
TI  - Suspected clopidogrel resistance in a patient with acute stent thrombosis.
AB  - BACKGROUND: A 67-year-old man with supraventricular tachycardia associated with
      angina underwent coronary angiographic assessment. This investigation revealed
      mild coronary artery disease in his left main coronary artery and significant
      stenosis of the ramus medianus (left intermediate artery). A drug-eluting stent
      was deployed and treatment with clopidogrel and eptifibatide started. The patient
      subsequently developed chest pain accompanied by hypotension, hypoxemia and
      electrocardiographic changes that indicated acute myocardial infarction.
      Emergency angiography revealed occlusion of the ramus medianus despite
      clopidogrel therapy. INVESTIGATIONS: Coronary angiography, hypercoagulable work
      up and platelet function tests. DIAGNOSIS: Acute stent thrombosis and suspected
      clopidogrel resistance, culminating in ST-segment elevation myocardial infarction
      after percutaneous coronary intervention. MANAGEMENT: Warfarin, aspirin and
      clopidogrel drug therapy.

PMID- 16568134
TI  - Weight cycling of athletes and subsequent weight gain in middleage.
AB  - OBJECTIVE: To study the effects of repeated cycles of weight loss and regain as
      young adults on long-term weight development. DESIGN: A follow-up study with
      questionnaires in 1985, 1995 and 2001. SETTING: Finland. SUBJECTS: A national
      cohort of 1838 male elite athletes who had represented Finland in major
      international sport competitions in 1920-1965, including 370 men engaged in
      sports in which weight-related performance classes are associated with weight
      cycling (boxers, weight lifters and wrestlers; further called as weight cyclers),
      and 834 matched control men with no athletic background. OUTCOME MEASURE: Weight
      change since the age of 20 years, body mass index (BMI) and prevalence of obesity
      and overweight. RESULTS: The weight cyclers gained 5.2 BMI units from age 20
      years to their maximum mean weight, which was at age 58.7 years. Corresponding
      figures for the controls were 4.2 BMI units at 58.5 years and for other athletes
      3.3 BMI units at age 62.5 years. The proportion of obese (BMI> or =30 kg/m(2))
      subjects was greatest among the weight cyclers both in 1985 and 1995. In 2001,
      the weight cyclers were more often obese than other athletes, but did not differ
      from the controls. The odds ratio for the weight cyclers to be obese compared to
      other athletes in 1985 was 3.18 (95% confidence intervals 2.09-4.83), and
      compared to the controls 2.0 (1.35-2.96). The enhanced weight gain of the weight
      cyclers was not accounted for by present health habits (smoking, alcohol use, use
      of high-fat milk or physical activity) or weight at age 20 years. CONCLUSIONS:
      Repeated cycles of weight loss and regain appear to enhance subsequent weight
      gain and may predispose to obesity. Chronic dieting with weight cycling may be
      harmful for permanent weight control.

PMID- 16568135
TI  - Genetic and environmental correlations between obesity phenotypes and age at
      menarche.
AB  - OBJECTIVE: To assess the extent that the genetic and environmental factors
      contribute to the phenotypic correlations between obesity traits and age at
      menarche (AAM), and also to examine the influence of AAM on obesity in both pre-
      and postmenopausal women. METHODS: F ive hundred and twelve pedigrees with 2667
      Caucasian female subjects from two to four generations were recruited. Fat mass
      and lean mass (both in kg) were measured by dual-energy X-ray absorptiometry
      scanner. Body mass index (BMI) (kg/m(2)) was calculated. We performed bivariate
      quantitative genetic analyses in the total sample containing 2667 Caucasian
      women. We also selected 206 unrelated premenopausal women and 140 unrelated
      postmenopausal women from the total sample, and computed the respective
      phenotypic correlation between obesity and AAM in these two subgroups. RESULTS:
      For fat mass, lean mass and BMI, we detected their significant negative genetic
      correlations with AAM after adjustment for significant covariates, which were 
      0.3170 (P<0.001), -0.1721 (P<0.05) and -0.3665 (P<0.001), respectively. However,
      their environmental correlations with AAM were all nonsignificant (P>0.05),
      ranging from -0.0016 to 0.0192. In the premenopausal subgroup, significant
      associations were observed between fat mass and AAM (rho=-0.231, P<0.01) as well
      as between BMI and AAM (rho=-0.257, P<0.01). In the postmenopausal subgroup, no
      such associations were observed. CONCLUSION: Our results for the first time
      suggested that significant phenotypic association between obesity phenotypes and
      AAM is mainly attributable to shared genetic rather than environmental factors,
      and AAM may have stronger effects on obesity phenotypes in pre- than in
      postmenopausal women.

PMID- 16568136
TI  - Maternal restriction of children's eating and encouragements to eat as the 'non
      shared environment': a pilot study using the child feeding questionnaire.
AB  - OBJECTIVE: This pilot study tested whether maternal feeding attitudes and styles
      towards children are part of the 'shared' or 'non-shared' home environment. A
      secondary aim was to test whether within-family differences in maternal feeding
      attitudes and styles relate to within-family differences in child weight status.
      METHODS: Mothers of 3- to 7-year-old sibling pairs (N=15 pairs) completed the
      Child Feeding Questionnaire (CFQ), which assessed feeding attitudes (perceived
      responsibility, perceived child overweight and child weight concern) and feeding
      styles (monitoring, restriction and pressure to eat) towards children. Mothers
      rated each sibling separately. Child weight and height were measured and
      converted to body mass index (BMI) z-scores. Intraclass correlations tested the
      familial associations for each CFQ subscale. Pearson's correlations tested
      whether within-family differences in CFQ subscales were related to within-family
      differences in child BMI z-scores. RESULTS: Perceived responsibility (rho=0.77,
      P=0.0004), perceived child overweight (rho=0.99, P<0.0001) and monitoring
      (rho=0.57, P=0.01) showed significant familial correlations. Mothers reported
      significantly greater weight concern (r=0.85, P=0.02) and reduced pressure to eat
      (r=-0.80, P=0.03) towards heavier than thinner children within families.
      CONCLUSION: Whether or not maternal feeding practices are shared or non-shared
      components of the home environment depends on the specific feeding domain being
      measured. Restrictive feeding practices and encouragements to eat by mothers
      might be tested as non-shared environmental variables in genetics studies of
      childhood obesity.

PMID- 16568137
TI  - Polymorphisms in the NPY and AGRP genes and body fatness in Dutch adults.
AB  - OBJECTIVE: To investigate the association between DNA polymorphisms in the NPY
      and AGRP genes and body fatness. DESIGN AND METHODS: The association between the
      AGRP Ala67Thr or the NPY Leu7Pro polymorphisms and indicators of body fatness
      (baseline leptin levels, body mass index (BMI) values and prevalence of
      overweight) are investigated in 582 participants of two large cohorts in The
      Netherlands (total 18 500 adult men and women), aged 20-40 years whose weight
      remained relatively constant or whose weight increased substantially (range 5.5
      47 kg) during a mean follow-up of 7 years. RESULTS: No consistent associations
      were found for the indicators of body fatness for men and women. Among women, BMI
      values, leptin levels and prevalence of overweight were not statistically
      different for carriers of the mutant alleles compared to that of the non
      carriers. Among men, carriers of the Thr67-allele of the AGRP gene had similar
      leptin levels, but higher BMI values compared to those with the genotyping
      Ala67/Ala67: mean adjusted BMI 25.6 kg/m2 (95% CI 24.3-27.0) vs 23.9 kg/m2 (23.6
      24.3). Also, the risk of being overweight at baseline tended to be higher for
      male carriers of the Thr67-allele of the AGRP gene (OR 2.52; 95% CI 0.86-7.4).
      Furthermore, male carriers of the Pro7-allele of the NPY gene had on average
      higher leptin levels and BMI values vs non-carriers of this allele: 4.7 microg/l
      (95% CI 3.7-6.0) and 25.7 kg/m2 (95% CI 24.4-27.0) vs 3.1 microg/l (95% CI 2.9
      3.4) and 23.9 kg/m2 (95% CI 23.5-24.3), respectively. These male carriers had
      also a higher risk on being overweight at baseline (OR 3.3 (95% CI 1.2-8.9))
      compared to non-carriers of the Pro7-allele. CONCLUSION: The consistent findings
      among men suggest that the NPY Leu7Pro polymorphism (or another linked marker)
      might be involved in the development of obesity at younger ages. The findings for
      the AGRP Ala67Thr were less consistent and need further investigation. Among
      women, these polymorphisms do not play an important role.

PMID- 16568138
TI  - The relationship between body mass index and educational level in young
      Portuguese males: 1995 and 1999 cohorts.
AB  - INTRODUCTION: Over the last decades, a progressive increase in height and weight
      has been observed throughout Europe. Increase in weight has been more marked
      however, with a resulting increase in overweight and obesity prevalence. RESULTS
      published have analyzed the relationship between body mass index (BMI) and
      educational level. Most studies indicate an inverse relationship between BMI and
      educational level in developed countries. OBJECTIVE: This study's main objective
      was to evaluate the relationship between BMI and educational level (years of
      schooling) in young Portuguese males in 1995 and 1999. METHODS: Transverse study
      of data (BMI and years of schooling) from the military inspection records of
      virtually the entire Portuguese male population with an average age of 20 years,
      examined in 1995 and 1999, totaling 81 363 and 71 254, respectively. Four classes
      of BMI (<20, 20-24.9, 25-29.9 and > or =30 kg/m2) and four schooling levels (<5,
      5-9, 10-12, and >12 years) were considered. We applied the chi2 test for
      associations between BMI and educational level and the odds ratio to quantify
      categorical variables. The significance level was 5%. RESULTS: In 1995, 15.2%
      were overweight (BMI> or =25 years), increasing to 20.8% in 1999. The percentage
      of obesity (BMI> or =30 years) was 1.4% in 1995 and 2.2% in 1999. The percentage
      of overweight and obesity increased directly in line with the increase in
      educational level, both in 1995 and 1999. In 1995, the percentage of subjects
      with obesity according to years of schooling was as follows: <5 years--1.4%; 5-9
      years--1.4%; 10-12 years--1.5% and >12 years--1.7%. In 1999, the results were as
      follows: <5 years--1.4%; 5-9 years--2.2%; 10-12 years--2.8% and >12 years--3.2%.
      CONCLUSIONS: We can conclude that the prevalence of overweight and obesity in
      young male Portuguese increased in the last decade and that, unlike most
      developed countries, the higher the level of education, the greater the
      percentage of overweight and obesity, both in 1995 and 1999.

PMID- 16568139
TI  - The effect of thalidomide on spinal cord ischemia/reperfusion injury in a rabbit
      model.
AB  - STUDY DESIGN: Randomized study. OBJECTIVES: To evaluate the effects of
      thalidomide on spinal cord ischemia/reperfusion injury via reduced TNF-alpha
      production. SETTING: Animal experimental laboratory, Clinical Research Institute
      of Seoul National University Hospital, Seoul, Korea. METHODS: Spinal cord
      ischemia was induced in rabbits by occluding the infrarenal aorta. Rabbits in
      group N did not undergo ischemic insult, but rabbits in groups C (the untreated
      group), THA, and THB underwent ischemic insult for 15 min. The THA and THB groups
      received thalidomide (20 mg/kg) intraperitoneally (i.p.) before ischemia, but
      only the THB group received thalidomide (i.p., 20 mg/kg) after 24 and 48 h of
      reperfusion. After evaluating neurologic functions at 1.5 h, 3, and 5 days of
      reperfusion, rabbits were killed for histopathologic examination and Western blot
      analysis of TNF-alpha. RESULTS: The THA and THB groups showed significantly less
      neurologic dysfunction than the C group at 1.5 h, 3, and 5 days of reperfusion.
      The number of normal spinal motor neurons in ventral gray matter was higher in
      THA and THB than in C, but no difference was observed between THA and THB.
      Western blot analysis showed a significantly higher level of TNF-alpha in C than
      in THA and THB at 1.5 h of reperfusion, but no difference was observed between C,
      THA, or THB at 3 or 5 days of reperfusion. CONCLUSION: Thalidomide treatment
      before ischemic insult reduces early phase ischemia/reperfusion injury of the
      spinal cord in rabbits.

PMID- 16568140
TI  - Modified Girdlestones-Taylor procedure for claw toes in spinal cord injury.
AB  - STUDY DESIGN: A combination of review of case notes and outpatient follow-up.
      OBJECTIVE: To evaluate the effectiveness of the modified Girdlestones-Taylor
      procedure in patients with spinal cord injury (SCI). SETTING: Princess Royal
      Spinal Injuries Centre (PRSIC), Northern General Hospital, Sheffield, UK.
      METHODS: Nine patients with claw toe deformities to 27 toes were treated at the
      PRSIC from 1996 to 2005. After examination of their medical records, their toes
      were assessed for pain, residual deformity and stiffness. They were also asked to
      grade their satisfaction with the surgical outcome. The results were tabulated.
      RESULTS: The average age of our series of patients was 43.3 years. The mean time
      from injury to surgery was 20.4 years and the mean time from surgery to last
      follow-up was 37.3 months. All our patients had good to excellent results, with
      over 70% of the toes having excellent results. CONCLUSION: The modified
      Girdlestones-Taylor procedure for claw toe correction appears to be a safe and
      effective treatment for patients with SCI.

PMID- 16568141
TI  - Cerebro-spinal decompression sickness: report of two cases.
AB  - STUDY DESIGN: Two case reports. OBJECTIVE: To describe two unusual cases of deep
      diving followed by cerebro-spinal decompression sickness (DCS). SETTING: Midlands
      Centre for Spinal Injuries, England. METHODS: Observation of the outcome of two
      different cases of cerebro-spinal DCS, who have received two different modalities
      of treatment. RESULTS: The first patient's symptoms developed after he surfaced,
      he was treated according to the US Navy treatment table 6. He also received
      steroids for almost 3 weeks. His MRI of the brain and spinal cord, which was
      performed within 24 h of injury did not show any abnormality, while a repeat MRI
      3 weeks later revealed abnormal signals in the brain and spinal cord. The second
      patient's symptoms started before he surfaced, he was treated with Comex 30
      treatment table for 14 days and received no steroids, his MRI was performed 3
      days after the injury showed high signals in the brain and spinal cord.
      CONCLUSION: Both divers developed cerebro-spinal dysfunction. They had
      encephalopathy (manifested by loss of consciousness), which indicates bilateral
      cerebral dysfunction. DCS can occur even when dives are conducted according to
      the procedures described by the US Navy. The use of high-dose steroids has not
      been formally tested in DCS; their use is controversial.

PMID- 16568142
TI  - The role of androgens or growth factors in the bone resorption process in recent
      spinal cord injured patients: a cross-sectional study.
AB  - STUDY DESIGN: This cross-sectional study compared the androgen and growth factor
      profiles and the bone turnover of patients with spinal cord injury (SCI) versus
      able-bodied controls (AB). OBJECTIVE: Determine whether androgens, GH, or either
      IGF-I or IGFBP-3, are implicated in bone turnover alteration in patients with
      recent SCI. SETTING: Propara Center, Montpellier, France. METHODS: In all, 16 men
      (31.3 years) with complete SCI, seven paraplegics and nine tetraplegics, who had
      sustained injury an average of 3 months earlier, and 12 AB who served as controls
      (27.5 years) participated. Androgens, growth hormone and its mediators were
      investigated. The bone resorption process was evaluated by urinary and plasma
      type I collagen C-telopeptide (CTXu, CTXp), while bone formation was evaluated by
      osteocalcin (OC) and bone alkaline phosphatase. RESULTS: Total testosterone (TT)
      and the free androgen index (FAI) were significantly lower in the SCI patients,
      whereas FSH was significantly higher (P<0.05). These hormonal variations were not
      related to the level of neurological lesion. There was no significant difference
      in GH, IGF-I, or IGFBP-3 levels. CTXu and CTXp indicated high bone resorption
      activity in the SCI patients (P<0.05). Regarding bone formation markers, only OC
      was affected by neurological lesion (P<0.05). Basal hormone levels did not
      correlate with markers of bone turnover. CONCLUSION: The high bone resorption
      process observed in SCI patients did not seem directly related to testicular
      endocrine abnormalities or an altered growth factor profile. Nevertheless, the
      reduced TT and FAI levels could be aggravating factors in the development of
      acute bone loss.

PMID- 16568143
TI  - Perceptual threshold to cutaneous electrical stimulation in patients with spinal
      cord injury.
AB  - STUDY DESIGN: Prospective experimental. OBJECTIVES: The aim of this study was to
      develop a quantitative sensory test (QST) that could be used for assessing the
      level and the density (degree of impairment) of spinal cord injury (SCI) and for
      monitoring neurological changes in patients with SCI. SETTING: National Spinal
      Injuries Centre, Stoke Mandeville Hospital, Buckinghamshire Hospitals NHS Trust,
      UK. METHODS: Perceptual threshold to 3 Hz cutaneous electrical stimulation was
      measured in 30 control subjects and in 45 patients with SCI at American Spinal
      Injuries Association (ASIA) sensory key points for selected dermatomes between C3
      and S2 bilaterally. Electrical perceptual threshold (EPT) was recorded as the
      lowest ascending stimulus intensity out of three tests at which the subject
      reported sensation. The level of SCI according to EPT results was established for
      right and left sides as the most caudal spinal segment at which patient's EPT was
      within the control range (mean +/- 2 standard deviation (SD)). The level of SCI,
      according to EPT, was then compared with clinical sensory level derived according
      to ASIA classification. RESULTS: In the control group, EPT depended on the
      dermatome tested and was lowest for T1 (1.01 +/- 0.23 mA, mean +/- SD) and
      highest for L5 (3.32 +/- 1.14 mA). There was strong correlation between
      corresponding right and left dermatomes and between repeated assessments. In the
      SCI group, the level of lesion according to EPT and clinical testing was the same
      in 43 of the 90 tests (48%). In 37 cases (41%), the EPT level was higher than the
      clinical level, and in 10 cases (11%), it was lower. Below the level of lesion in
      incomplete SCI and in the zone of partial preservation in complete SCI, the EPT
      values in most dermatomes were raised compared with the control group.
      CONCLUSIONS: EPT is a simple, reproducible QST that can assess both the level and
      the density of SCI. It seems to add sensitivity and resolution to the standard
      clinical testing and could be a useful adjunct in longitudinal monitoring of
      patients with SCI for research purposes during natural recovery and therapeutic
      interventions. SPONSORSHIP: International Spinal Research Trust (ISRT), UK, Grant
      CLI001.

PMID- 16568144
TI  - Unstable baseline blood pressure in chronic tetraplegia.
AB  - STUDY DESIGN: Case-control. OBJECTIVE: Tetraplegic patients are subject to
      episodes of autonomic dysreflexia and postural hypotension. It is suggested that
      these patients sustain, in addition, unstable baseline blood pressure (BP) that
      is independent of symptoms and body position. METHODS: BP monitoring was
      conducted in 10 tetraplegic patients, motor and sensory complete (American Spinal
      Injury Association (ASIA) A) (Group A), and five paraplegic at T8-T10 levels,
      ASIA A (Group B). A SpaceLabs automatically inflating pneumatic cuff recorded arm
      pressures at 10-30 min intervals in the daytime, sitting position and at 30 min
      intervals in the night-time, recumbent position. Group mean arterial pressure
      (MAP) and MAP standard deviation (MAP variation) for sitting and recumbent
      positions were compared. RESULTS: Sitting the MAP for Group A was less than that
      of Group B; 87+/-9 versus 108+/-7 mmHg, P<0.01. However, MAP variability for
      Group A was greater than for Group B; 17+/-4 (20% of MAP) versus 13+/-2 mmHg (12%
      of MAP), P=0.04. In the recumbent position, the MAP for Group A was similar to
      that for Group B; 87+/-13 versus 97+/-7 mmHg, P=0.16. However, MAP variability
      for Group A remained higher than for Group B; 13+/-3 (20% of MAP) versus 8+/-2
      mmHg (8% of MAP), P=0.02. CONCLUSION: Tetraplegic patients demonstrate unstable
      BP in either the sitting or recumbent position compared with low thoracic
      paraplegic patients.

PMID- 16568145
TI  - Disability and determinants of gait performance in tropical spastic
      paraparesis/HTLV-I associated myelopathy (HAM/TSP).
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: The aim of this survey is to describe
      the disability profile in a group of tropical spastic paraparesis/HTLV-I
      associated myelopathy patients, identifying the requirements for community
      ambulation. SETTING: Tertiary care unit, Rio de Janeiro, Brazil. METHODS: Seventy
      two patients were assessed (49 female and 23 male), referred by tertiary care
      centers, when a clinical protocol was applied. RESULTS: The sample had an average
      age of 40 years and an average of 137 months of duration of the disease. The most
      prevalent aspects of disability found were in gait and sphincter control areas. A
      total of 72% of the patients were community ambulators and 17% were restricted to
      wheel chair. Age, strength and low-back pain interfere in activities of daily
      living (P<0.05). A positive correlation was found between community ambulation
      and the knee extensors (r=0.80) and ankle plantar flexors (r=0.74). Strength,
      age, low-back pain, duration of disease, asymmetric onset of the symptoms and
      spasticity interfered in the ability to walk (P<0.05). A rehabilitation program
      was proposed focusing on modifiable factors that affect disability level.
      CONCLUSION: It was possible to describe the profile of disability in this group
      of patients, identifying the requirements to the community ambulation.

PMID- 16568146
TI  - Prostatic carcinosarcoma 15 years after combined external beam radiation and
      brachytherapy for prostatic adenocarcinoma: a case report.
AB  - A 65-year-old man with a history of combined pelvic external beam radiation
      therapy (EBRT) and brachytherapy for prostatic adenocarcinoma 15 years prior
      underwent total pelvic exenteration for presumed rectal sarcoma with prostatic
      invasion. Pathology revealed carcinosarcoma of prostatic origin. This patient
      exhibited the longest reported interval between initial presentation with
      prostatic adenocarcinoma and development of carcinosarcoma. This case is also the
      first reported case of prostatic carcinosarcoma occurring after combined EBRT and
      brachytherapy. The increasing use of such combination high-dose radiation therapy
      may potentially lead to an increased incidence of secondary malignancies such as
      prostatic carcinosarcoma in the future.

PMID- 16568147
TI  - PSA velocity and PSA slope.
AB  - The aim of this study is to compare different tools for evaluating prostate
      specific antigen (PSA) increase or decrease, such as PSA velocity and PSA slope.
      This study was conducted on 312 male patients evaluated with transrectal
      ultrasound-guided biopsy of prostate with six or more cores. Patients with at
      least three consecutive PSA measurements in at least 18 months entered the study.
      Prostate-specific antigen slope was estimated by the slope of the least-square
      regression line fit to PSA versus time in years; PSA velocity was calculated with
      3 or more PSA arrays. Median age was 66 years (range 45-86). Overall 67 patients
      were affected by primary prostate cancer, 245 were controls without prostate
      cancer. Prostate-specific antigen slope and PSA velocity were significantly
      higher in patients with prostate cancer than in controls. At the ROC analysis,
      PSA slope evidenced better results than PSA velocity (area under the curve (AUC)
      0.743 for PSA slope; AUC 0.663 for PSA velocity; P=0.037). At PSA slope
      (calculated with the least-square fit) equal to zero, the sensitivity resulted as
      being 94% with a specificity of 38.8%. In conclusion prostate-specific antigen
      slope calculated with three or more PSA assays permits longitudinal evaluation of
      PSA for prostate diagnosis. Prostate-specific antigen slope improves both
      sensitivity and specificity in prostate cancer diagnosis, compared with PSA
      velocity.

PMID- 16568148
TI  - Overview of the pharmacogenetics of asthma treatment.
AB  - Asthma affects approximately 300 million individuals worldwide. Medications
      comprise a substantial portion of asthma expenditures. Despite the availability
      of three primary therapeutic classes of medications, there are a significant
      number of nonresponders to therapy. Available data, as well as previous
      pharmacogenetic studies, suggest that genetics may contribute as much as 60-80%
      to the interindividual variability in treatment response. In this methodologic
      review, after providing a broad overview of the asthma pharmacogenetics
      literature to date, we describe the application of a novel family-based screening
      algorithm to the analysis of pharmacogenetic data and highlight our approach to
      identifying and verifying loci influencing asthma treatment response. This
      approach seeks to address issues related to multiple comparisons, statistical
      power, population stratification, and failure to replicate from which previous
      population-based or case-control pharmacogenetic association studies may suffer.
      Identification of such replicable loci is the next step towards the goal of
      'individualized therapy' for asthma.

PMID- 16568149
TI  - Hippocampal upregulation of the cyclooxygenase-2 gene following neonatal
      clomipramine treatment (a model of depression).
AB  - Although a putative role has been attributed to inflammation in the pathogenesis
      of depressive disorders, the relationship of prostaglandins, known mediators of
      inflammation, and depression has not been elucidated. Clomipramine is an
      antidepressive drug with a pro-depressive paradoxical effect in adult rats when
      administrated neonatally. Using this effect as a model of depression, we
      investigated the differential expression of the cyclooxygenase (COX-2) gene in
      rat brains. Rats injected neonatally with clomipramine showed depressive-like
      symptoms in adulthood, as well as decreased levels of the brain-derived
      neurotrophic factor (BDNF) and a quantitative differential expression of the COX
      2 gene (Real Time PCR) and protein (immunohistochemistry) in the hippocampus. As
      evidenced, the relationship between a key enzyme in the prostaglandin synthesis
      and biological and behavioral depression-like changes opens an interesting line
      of investigation regarding the molecular bases of depression and its potential
      treatment through immunomodulatory drugs.

PMID- 16568150
TI  - Experience with voluntary and required genomic data submissions to the FDA:
      summary report from track 1 of the third FDA-DIA-PWG-PhRMA-BIO pharmacogenomics
      workshop.

PMID- 16568151
TI  - A complex polymorphic region in the brain-derived neurotrophic factor (BDNF) gene
      confers susceptibility to bipolar disorder and affects transcriptional activity.
AB  - Previous studies have suggested that genetic variations in the brain-derived
      neurotrophic factor (BDNF) gene may be associated with several neuropsychiatric
      diseases including bipolar disorder. The present study examined a microsatellite
      polymorphism located approximately 1.0 kb upstream of the translation initiation
      site of the BDNF gene for novel sequence variations, association with bipolar
      disorder, and effects on transcriptional activity. Detailed sequencing analysis
      revealed that this polymorphism is not a simple dinucleotide repeat, but it is
      highly polymorphic with a complex structure containing three types of
      dinucleotide repeats, insertion/deletion, and nucleotide substitutions that gives
      rise to a total of 23 novel allelic variants. We obtained evidence supporting the
      association between this polymorphic region (designated as BDNF-linked complex
      polymorphic region (BDNF-LCPR)) and bipolar disorder. One of the major alleles
      ('A1' allele) was significantly more common in patients than in controls (odds
      ratio 2.8, 95% confidential interval 1.5-5.3, P=0.001). Furthermore, a luciferase
      reporter gene assay in rat primary cultured neurons suggests that this risk
      allele (A1) has a lower-transcription activity, compared to the other alleles.
      Our results suggest that the BDNF-LCPR is a functional variation that confers
      susceptibility to bipolar disorder and affects transcriptional activity of the
      BDNF gene.

PMID- 16568152
TI  - Gas-phase ion/ion reactions of multiply protonated polypeptides with metal
      containing anions.
AB  - Gas-phase reactions of multiply protonated polypeptides and metal containing
      anions represent a new methodology for manipulating the cationizing agent
      composition of polypeptides. This approach affords greater flexibility in forming
      metal containing ions than commonly used methods, such as electrospray ionization
      of a metal salt/peptide mixture and matrix-assisted laser desorption. Here, the
      effects of properties of the polypeptide and anionic reactant on the nature of
      the reaction products are investigated. For a given metal, the identity of the
      ligand in the metal containing anion is the dominant factor in determining
      product distributions. For a given polypeptide ion, the difference between the
      metal ion affinity and the proton affinity of the negatively charged ligand in
      the anionic reactant is of predictive value in anticipating the relative
      contributions of proton transfer and metal ion transfer. Furthermore, the binding
      strength of the ligand anion to charge sites in the polypeptide correlates with
      the extent of observed cluster ion formation. Polypeptide composition, sequence,
      and charge state can also play a notable role in determining the distribution of
      products. In addition to their usefulness in gas-phase ion synthesis strategies,
      the reactions of protonated polypeptides and metal containing anions represent an
      example of a gas-phase ion/ion reaction that is sensitive to polypeptide
      structure. These observations are noteworthy in that they allude to the
      possibility of obtaining information, without requiring fragmentation of the
      peptide backbone, about ion structure as well as the relative ion affinities
      associated with the reactants.

PMID- 16568153
TI  - Powered lower limb orthoses for gait rehabilitation.
AB  - Bodyweight supported treadmill training has become a prominent gait
      rehabilitation method in leading rehabilitation centers. This type of locomotor
      training has many functional benefits but the labor costs are considerable. To
      reduce therapist effort, several groups have developed large robotic devices for
      assisting treadmill stepping. A complementary approach that has not been
      adequately explored is to use powered lower limb orthoses for locomotor training.
      Recent advances in robotic technology have made lightweight powered orthoses
      feasible and practical. An advantage to using powered orthoses as rehabilitation
      aids is they allow practice starting, turning, stopping, and avoiding obstacles
      during overground walking.

PMID- 16568154
TI  - Diabetic cardiomyopathy: where are we 40 years later?
AB  - Diabetic cardiomyopathy is a cardiac disease that arises as a result of the
      diabetic state, independent of vascular or valvular pathology. It manifests
      initially as asymptomatic diastolic dysfunction, which progresses to symptomatic
      heart failure. The compliance of the heart wall is decreased and contractile
      function is impaired. The pathophysiology is incompletely understood, but appears
      to be initiated both by hyperglycemia and changes in cardiac metabolism. These
      changes induce oxidative stress and activate a number of secondary messenger
      pathways, leading to cardiac hypertrophy, fibrosis and cell death. Alterations in
      contractile proteins and intracellular ions impair excitation-contraction
      coupling, while decreased autonomic responsiveness and autonomic neuropathy
      impair its regulation. Extensive structural abnormalities also occur, which have
      deleterious mechanical and functional consequences.

PMID- 16568155
TI  - Nav1.5/R1193Q polymorphism is associated with both long QT and Brugada syndromes.
AB  - BACKGROUND: Brugada syndrome (BS) and long QT syndrome (LQTS) are electrical
      disorders with a genetic background. They are revealed on surface
      electrocardiograms as either right bundle branch block and ST segment elevation
      in the right pericardial leads (V1, V2 and V3) in BS or as a long QTc interval on
      all 12 leads of the electrocardiogram in LQTS. Both BS and LQTS can lead to
      syncope and even sudden death. The R1193Q SCN5A variant was recently associated
      with LQTS, BS and cardiac conductance disease. OBJECTIVE AND METHODS: The aim of
      the present study was to screen the SCN5A gene from two patients -- one with BS
      and the other showing signs of a BS/LQTS phenotype -- for mutations, and to
      characterize the effect of the mutations on channel function using the patch
      clamp technique. RESULTS: A heterozygous mutation (R1193Q) was identified on the
      SCN5A gene in both patients. The R1193Q polymorphism was absent in 100 unrelated
      control alleles, suggesting that it has a low frequency in the French Canadian
      population. Mutant R1193Q expressed in tsA201 cells, which was studied using the
      patch clamp technique, had a persistent sodium current that could account for the
      QTc prolongation. A shift of steady-state inactivation toward more hyperpolarized
      voltages was observed that could explain the BS phenotype. CONCLUSION: The R1193Q
      polymorphism is definitively associated with cardiac electrical abnormalities.

PMID- 16568156
TI  - A comparison of Canadian and American guidelines for lipid management using data
      from the National Cholesterol Education Program Evaluation ProjecT Utilizing
      Novel E-technology (NEPTUNE) II survey.
AB  - BACKGROUND: The United States' National Cholesterol Education Program (NCEP)
      Adult Treatment Panel III and the Canadian Working Group on Hypercholesterolemia
      and Other Dyslipidemias (CWG) have each issued guidelines for the treatment of
      dyslipidemia. OBJECTIVE: The present analysis compared the percentage of patients
      reaching target lipid levels according to NCEP and CWG guidelines among
      participants of the NCEP Evaluation ProjecT Utilizing Novel E-technology
      (NEPTUNE) II, a survey performed in the United States. METHODS: American
      physicians who were high prescribers of lipid-modifying medications (n=376) each
      enrolled 10 to 20 consecutive patients from February to September 2003. Medical
      information, laboratory measurements and treatment plans associated with a single
      office visit were entered into a personal digital assistant and uploaded to a
      central database via the Internet. RESULTS: Under both sets of guidelines,
      treatment success was strongly related to risk category (P<0.001). Treatment goal
      achievement in the low-risk (zero or one risk factor) and moderate-risk (two or
      more risk factors) categories was not substantially different between NCEP and
      CWG guidelines; however, in the high-risk category (coronary artery disease [CAD]
      and risk equivalents [RE]), CWG treatment goals were met less frequently than
      NCEP goals. NCEP combined low-density lipoprotein cholesterol and non-high
      density lipoprotein cholesterol treatment goals were met by 39% of
      hypertriglyceridemic patients (27% in the CAD + CAD RE category). CWG combined
      low-density lipoprotein cholesterol and total cholesterol/high-density
      lipoprotein cholesterol ratio treatment goals were met by 38% of
      hypertriglyceridemic patients (19% in the CAD + CAD RE category). CONCLUSIONS:
      These data indicate substantial underachievement of treatment goals by patients
      at high risk under both the CWG and NCEP guidelines. The lower frequency of
      treatment success in high-risk patients according to the CWG definition indicates
      that more aggressive treatment is needed to reach CWG goals.

PMID- 16568157
TI  - Predictors of self-reported noncompliance with antihypertensive drug treatment: a
      prospective cohort study.
AB  - BACKGROUND: Persistence and compliance are different aspects of the broader
      concept of adherence to drug treatment. In a prior study, determinants of
      nonpersistence in a group of patients newly prescribed antihypertensive
      medications were examined. OBJECTIVE: To determine noncompliance among those who
      were persistent with therapy. METHODS: A prospective cohort study was conducted,
      in which individuals prescribed a new antihypertensive monotherapy were
      identified through a network of 173 pharmacies. Participants were interviewed by
      telephone twice during a three-month period. At the end of this period,
      individuals who reported still taking the medication initially prescribed were
      included in the analysis. Self-reported noncompliance was measured at three
      months. Data were analyzed using a multivariate logistic regression model.
      RESULTS: Of 509 eligible participants, 118 (23.2%) reported noncompliance with
      their drug treatment. Noncompliance was significantly associated with the use of
      angiotensin-converting enzyme inhibitors (adjusted OR [AOR] 3.0; 95% CI 1.17 to
      7.92) compared with the angiotensin II receptor blocker losartan, and with the
      belief that hypertension is not a risk factor for cardiovascular diseases (AOR
      2.0; 95% CI 1.21 to 3.33). On the other hand, noncompliance was inversely
      associated with the use of more than four pills of medication per day (AOR 0.3;
      95% CI 0.15 to 0.64). CONCLUSIONS: Compliance with drug treatment could be
      improved by proper selection of medication, and by attempts to correct the false
      perceptions patients may have about hypertension. Further research is needed to
      better understand the clinical significance of a higher number of pills as a
      predictor of good compliance. Further research is also needed using different
      means of measuring noncompliance.

PMID- 16568158
TI  - Unequal access to interventional cardiac care in Nova Scotia in patients with
      acute myocardial infarction complicated by cardiogenic shock.
AB  - BACKGROUND: The optimal treatment of cardiogenic shock (CS) complicating acute
      myocardial infarction (AMI) remains controversial and continues to be associated
      with a high mortality rate. The present study evaluated the outcomes of all
      patients having AMI complicated by CS in a single Canadian province. METHODS: All
      consecutive patients diagnosed with AMI and CS from October 1997 to December 2002
      in Nova Scotia were included in the present study. The Improving Cardiac Outcomes
      in Nova Scotia (ICONS) registry was used as the principal source of data. The
      outcome of interest was in-hospital mortality. RESULTS: During the study period,
      a total of 11,300 patients with AMI were identified, with 707 complicated by CS,
      for an incidence of AMI+CS of 6.3%. The overall mortality rate for patients with
      AMI+CS was 60.1%. Multivariate regression analysis identified age older than 65
      years (OR 2.0; 95% CI 1.4 to 2.9) and renal insufficiency (OR 2.1; 95% CI 1.4 to
      3.2) as independent predictors of mortality, while access to invasive cardiac
      care (defined as admission or transfer to the only cardiac catheterization
      capable centre in Halifax, Nova Scotia) was found to be an independent predictor
      of survival (OR 0.4; 95% CI 0.3 to 0.5). Access to invasive cardiac care was
      limited to 414 (59%) patients, 250 (35%) of whom actually underwent cardiac
      catheterization. CONCLUSIONS: Admissions to a tertiary care centre that can
      provide invasive care was independently associated with improved survival, and
      older age and renal insufficiency were associated with death among patients with
      AMI and CS.

PMID- 16568159
TI  - Aspergillus fumigatus pacemaker lead endocarditis: a case report and review of
      the literature.
AB  - The diagnosis of fungal endocarditis requires a high index of clinical suspicion.
      Rarely, pacemaker implantation may be a risk factor for the development of fungal
      endocarditis. A 71-year-old man with a history of multiple transvenous pacemaker
      manipulations and fever of an uncertain source is described. A diagnosis of
      culture-negative pacemaker endocarditis was established only after repeat
      transthoracic echocardiography. Amphotericin B was instituted; however, the
      patient developed a cerebral infarct and died. Postmortem examination
      demonstrated Aspergillus fumigatus within a large pacemaker lead thrombus,
      tricuspid and aortic valve vegetations, and septic pulmonary and renal emboli.
      The present report describes the clinical and pathological features of a rare
      case of Aspergillus fumigatus pacemaker lead endocarditis and suggests that
      serial echocardiograms may be effective in the early detection of pacemaker lead
      vegetations. The diagnostic features and therapeutic management of pacemaker lead
      endocarditis are reviewed.

PMID- 16568160
TI  - An introduction to thiol redox proteins in the endoplasmic reticulum and a review
      of current electrochemical methods of detection of thiols.
AB  - This aim of this paper is to expound the complexity of thiol redox systems in the
      endoplasmic reticulum of eukaryotic cells to the electroanalytical community. A
      summary of the state of the art in electrochemical methods for detection of
      thiols gives an insight into the challenges that need to be addressed to bridge
      the disparity between current analytical techniques and applications in a 'real'
      biological scenario.

PMID- 16568161
TI  - Wireless excitation of quartz crystals immersed in an aqueous fluid.
AB  - A novel toroidal coil geometry able to induce remote acoustic waves in quartz
      crystals has been evaluated for the development of (bio)sensors. Remote acoustic
      generation in air was obtained for two alternative toroidal coils, with
      corresponding electrical impedance changes of 40 Omega for a PDMS- and 140 Omega
      for a ferrite-supported toroid respectively. It was found that the range of
      remote acoustic generation relative to the spiral coil standard was much
      improved, increasing the axial separation of their resonant sensing element from
      0.1 mm to 20 mm, thereby allowing electromagnetic wave penetration across glass
      walls and fluid media to be utilised. Consideration of the transduction
      mechanism, along with measured cyclic changes in acoustic signal as a function of
      rotation, indicated that the large PDMS toroidal coil produced an asymmetric
      electric field. It was shown for the first time that a quartz crystal blank fully
      immersed in an aqueous fluid could support chemically sensitive shear acoustic
      standing waves that were excited and detected remotely. A signal to noise ratio
      of 30 ratio 1 at 20.13 MHz was achieved by placing a ferrite supported toroidal
      coil on the lower side of a glass beaker containing a 12 x 0.25 mm AT crystal
      blank and 1 mL of water. This discovery allows wireless shear acoustic wave
      measurements to be performed with total separation between the electronic
      detection system and assays undertaken in fluidic systems.

PMID- 16568162
TI  - Amperometric choline biosensor fabricated through electrostatic assembly of
      bienzyme/polyelectrolyte hybrid layers on carbon nanotubes.
AB  - We report a flow injection amperometric choline biosensor based on the
      electrostatic assembly of the choline oxidase (ChO) enzyme and a bienzyme of ChO
      and horseradish peroxidase (HRP) onto multi-wall carbon nanotubes (MWCNT)
      modified glassy carbon (GC) electrodes. These choline biosensors were fabricated
      by immobilization of enzymes on the negatively charged MWCNT surface through
      alternately assembling a cationic poly(diallydimethylammonium chloride) (PDDA)
      layer and an enzyme layer. Using this layer-by-layer assembling approach, a
      bioactive nanocomposite film of PDDA/ChO/PDDA/HRP/PDDA/CNT (ChO/HRP/CNT) and
      PDDA/ChO/PDDA/CNT (ChO/CNT) was fabricated on the GC surface. Owing to the
      electrocatalytic effect of carbon nanotubes, the measurement of faradic responses
      resulting from enzymatic reactions has been realized at low potential with
      acceptable sensitivity. The ChO/HRP/CNT biosensor is more sensitive than the
      ChO/CNT one. Experimental parameters affecting the sensitivity of biosensors,
      e.g., applied potential, flow rate, etc., were optimized and potential
      interference was examined. The response time for this choline biosensor is fast
      (few seconds). The linear range of detection for the choline biosensor is from
      5.0 x 10(-5) to 5.0 x 10(-3) M and the detection limit is about 1.0 x 10(-5) M.

PMID- 16568163
TI  - Homogenous rapid detection of nucleic acids using two-color quantum dots.
AB  - We report a homogenous method for rapid and sensitive detection of nucleic acids
      using two-color quantum dots (QDs) based on single-molecule coincidence
      detection. The streptavidin-coated quantum dots functioned as both a nano
      scaffold and as a fluorescence pair for coincidence detection. Two biotinylated
      oligonucleotide probes were used to recognize and detect specific complementary
      target DNA through a sandwich hybridization reaction. The DNA hybrids were first
      caught and assembled on the surface of 605 nm-emitting QDs (605QDs) through
      specific streptavidin-biotin binding. The 525 nm-emitting QDs (525QDs) were then
      added to bind the other end of DNA hybrids. The coincidence signals were observed
      only when the presence of target DNA led to the formation of 605QD/DNA
      hybrid/525QD complexes. In comparison with a conventional QD-based assay, this
      assay provided high detection efficiency and short analysis time due to its high
      hybridization efficiency resulting from the high diffusion coefficient and no
      limitation of temperature treatment. This QD-based single-molecule coincidence
      detection offers a simple, rapid and ultra sensitive method for genomic DNA
      analysis in a homogenous format.

PMID- 16568164
TI  - Towards biochemical reaction monitoring using FT-IR synchrotron radiation.
AB  - A lab-on-a-chip device made of CaF2 windows and SU-8 polymer was used for fluid
      lamination to achieve rapid mixing of two streamlines with a cross section of 300
      x 5 microm each. Time resolved measurements of the induced chemical reaction was
      achieved by applying constant feeding low flow rates and by on-chip measurement
      at defined distances after the mixing point. Synchrotron IR microscopic detection
      was employed for direct and label-free monitoring of (bio)chemical reactions.
      Furthermore, using synchrotron IR microscopy the measurement spot could be
      reduced to the diffraction limit, thus maximizing time resolution in the
      experimental set-up under study. Based on computational fluid dynamic simulations
      the principle of the set-up is discussed. Experimental results on the basic
      hydrolysis of methyl chloroacetate proved the working principle of the
      experimental set-up. First results on the interaction between the antibiotic
      vancomycin and a tripeptide (Ac2KAA) involved in the build up of the membrane
      proteins of gram-positive bacteria are presented.

PMID- 16568165
TI  - Luminescence temperature sensing using poly(vinyl alcohol)-encapsulated Ru(bpy)3
      2+ films.
AB  - The ruthenium(II) diimine complexes, such as ruthenium(II) tris(bipyridyl),
      Ru(bpy)3 2+, possess highly luminescent excited states that are not only readily
      quenched by oxygen but also by an increase in temperature. The former effect can
      be rendered insignificant by encapsulating the complex in an oxygen impermeable
      polymer, although encapsulation often leads also to a loss of temperature
      sensitivity. The luminescence properties of Ru(bpy)3 2+ encapsulated in PVA were
      studied as a function of oxygen concentration and temperature and found to be
      independent of the former, but still very sensitive towards the latter. The
      results were fitted to an established Arrhenius-type equation, based on thermal
      quenching of the emitting state by a slightly higher (DeltaE= 3100 cm(-1))3d-d
      state that deactivates very rapidly (10(-13) s)via a non-radiative process.

PMID- 16568166
TI  - Ultrasound-enhanced flow injection chemiluminescence for determination of
      hydrogen peroxide.
AB  - A novel ultrasonic flow injection chemiluminescence (FI-CL) manifold for
      determining hydrogen peroxide (H2O2) has been designed and evaluated.
      Chemiluminescence obtained from the luminol-H2O2-cobalt(II) reaction was enhanced
      by applying 120 W of ultrasound for a period of 4 s to the reaction coil in the
      FI-CL system and this enhancement was verified by comparison with an identical
      manifold without ultrasound. The system was developed for determining ultra-trace
      levels of H2O2 and a calibration curve was obtained with a linear portion over
      the range of 10-200 nmol L(-1) H2O2 (correlation coefficient 0.9945). The
      detection limit (3sigma) and the quantification limit (LOQ) were found to be 1 x
      10(-9) and 3.3 x 10(-9) mol L(-1) respectively and the relative standard
      deviation was 1.37% for 2 x 10(-7) mol L(-1) H2O2 (n = 10). The method was
      applied to the determination of trace amounts of H2O2 in purified water and
      natural water samples without any special pre-treatments.

PMID- 16568167
TI  - A hyphenated flow-through analytical system for the study of the mobility and
      fractionation of trace and major elements in environmental solid samples.
AB  - A flow-through hyphenated analytical method has been tested that enables not only
      the accelerated and efficient fractionation of trace elements (TE) species in
      environmental solids to be achieved but allows real-time studies on the leaching
      process to be made. Rotating coiled columns (RCC), earlier used mainly in
      countercurrent chromatography, have been successfully applied to the dynamic
      fractionation of heavy metals in soil, sediment, and sludge samples. A ground
      solid sample (about 0.5 g) was retained in a PTFE rotating column as the
      stationary phase whereas different aqueous eluents, chosen according to recent
      data on the selectivity of leachants, were continuously pumped through. Elements
      were determined in the effluent on-line by inductively coupled plasma atomic
      emission spectrometry (ICP-AES). Since the flow rates used in the RCC are in good
      agreement with those needed for cross-flow nebulization in the ICP-AES
      spectrometer, both devices were coupled directly without any additional interface
      systems. Simultaneous investigation of the elution profiles of trace and major
      elements has made it possible to study the elements association in separated
      fractions and hence to prove the efficacy of extractants and their selectivity
      toward targeted mineralogical phases of samples. The close association of heavy
      metals with Mn oxides in the sediment and sludge samples was confirmed. The time
      resolved dissolution of different organic complexes of metals was observed for
      the sediment sample. It was found that in sediment and sludge samples the
      dynamics of iron release under the action of Tamm's reagent is somewhat different
      from that of aluminium. In addition, the proposed method can also be applied to
      develop effective leaching schemes and in the analysis of environmental solids
      for risk assessment of their contaminants addressed to water quality and
      bioavailability.

PMID- 16568168
TI  - Detection of As(III) via oxidation to As(V) using platinum nanoparticle modified
      glassy carbon electrodes: arsenic detection without interference from copper.
AB  - The electrochemical detection of As(III) was investigated on a platinum
      nanoparticle modified glassy carbon electrode in 1 M aqueous HClO4. Platinum
      nanoparticle modified glassy carbon electrodes were prepared by potential cycling
      in 0.1 M aqueous KCl containing 1 mM K2PtCl6. In each potential cycle, the
      potential was held at + 0.5 V for 0.01 s and at -0.7 V for 10 s. 25 cycles were
      optimally used to prepare the electrodes. The resulting electrode surfaces were
      characterized with AFM. The response to arsenic(III) on the modified electrode
      was examined using cyclic voltammetry and linear sweep voltammetry. By using the
      As(III) oxidation peak for the analytical determination, there is no interference
      from Cu(II) if present in contrast to the other metal surfaces (especially gold)
      typically used for the detection of arsenic; Cu(II) precludes the use of the
      As(0) to As(III) peak for quantitative anodic stripping voltammetry measurements
      due to the formation of Cu3As2 and an overlapping interference peak from the
      stripping of Cu(0). After optimization, a LOD of 2.1 +/- 0.05 ppb was obtained
      using the direct oxidation of As(III) to As(V), while the World Health
      Organization's guideline value of arsenic for drinking water is 10 ppb,
      suggesting the method may have practical utility.

PMID- 16568169
TI  - Microdialysis hollow fiber as a macromolecule trap for on-line coupling of solid
      phase microextraction and capillary electrophoresis.
AB  - On-line coupling of solid phase microextraction (SPME) and capillary
      electrophoresis (CE) is highly desirable due to the apparent advantages of the
      two techniques particularly in the context of microanalysis. However, the
      hyphenation is a significant challenge, because of band broadening and analyte
      carryover caused by the slow kinetics of analyte desorption in liquid phase. A
      novel strategy was presented in this study to overcome these problems. Analytes
      desorbed from an SPME fiber, which was held by an adapter, were first transferred
      by electrophoretic migration into a short piece of microdialysis hollow fiber,
      which was located at the inlet of a CE system. Analytes with molecular weights
      greater than the molecular weight cut-off of the microdialysis material were
      trapped in the microdialysis hollow fiber due to the dialysis effect. Then, under
      another electric field with different electrode polarity, the analytes trapped in
      the microdialysis hollow fiber migrated into the separation capillary and were
      separated. In the coupling approach, the microdialysis hollow fiber functioned as
      a macromolecule trap and a sample pre-concentrator as well. Band broadening was
      eliminated because the initial sample volume was very small (at nL level).
      Meanwhile, analyte carryover was eliminated because the desorption time could be
      as long as needed. Coupling of SPME with CE including two modes, capillary zone
      electrophoresis (CZE) and capillary isoelectric focusing (CIEF), was successfully
      demonstrated with proteins as test analytes. High efficiency and high resolution
      were obtained. The detection limits with UV absorbance whole-column imaging
      detection were 3.0 x 10(-7) and 3.0 x 10(-8) M (S/N = 3) for beta-lactoglobulin A
      and ovalbumin, respectively.

PMID- 16568170
TI  - Moving window cross validation: a new cross validation method for the selection
      of a rational number of components in a partial least squares calibration model.
AB  - A new cross validation method called moving window cross validation (MWCV) is
      proposed in this study, as a novel method for selecting the rational number of
      components for building an efficient calibration model in analytical chemistry.
      This method works with an innovative pattern to split a validation set by a
      number of given windows that move synchronously along proper subsets of all the
      samples. Calculations for the mean value of all mean squares error in cross
      validations (MSECVs) for all splitting forms are made for different numbers of
      components, and then the optimal number of components for the model can be
      selected. Performance of MWCV is compared with that of two cross validation
      methods, leave-one-out cross validation (LOOCV) and Monte Carlo cross validation
      (MCCV), for partial least squares (PLS) models developed on one simulated data
      set and two real near-infrared (NIR) spectral data sets. The results reveal that
      MWCV can avoid a tendency to over-fit the data. Selection of the optimal number
      of components can be easily made by MWCV because it yields a global minimum in
      root MSECV at the optimal number of components. Changes in the window size and
      window number of MWCV do not greatly influence the selection of the number of
      components. MWCV is demonstrated to be an effective, simple and accurate cross
      validation method.

PMID- 16568171
TI  - Modified secured principal component regression for detection of unexpected
      chromatographic features in herbal fingerprints.
AB  - Secured principal component regression is modified for the qualitative analysis
      of chromatographic fingerprint data sets of herbal samples with residual
      concentrations. After chromatographic shift-correction and autoscaling are
      performed on the data, this modified secured principal component regression
      (msPCR) can detect unexpected chromatographic features in various herbal
      fingerprints. The successful application of msPCR to two real herbal medicines of
      Erigeron breviscapus from different geographical origins and Ginkgo biloba from
      various sources or vendors demonstrates that the proposed method can detect
      reasonably unexpected features differing from the regulars or not being modeled.
      From a chemical point of view, the causes have also been explained to corroborate
      the results. Moreover, it presents a viable approach for the qualitative
      evaluation of diverse herbal objects with a regular class of chromatographic
      fingerprints.

PMID- 16568172
TI  - Analytical performance characteristics of nanoelectrospray emitters as a function
      of conductive coating.
AB  - As miniaturization of electrospray continues to become more prevalent in the mass
      spectrometry arsenal, numerous types of conductive coatings have been developed
      with miniaturized electrospray emitters. Different conductive coatings have
      different properties that may lead to differences in analytical performance. This
      paper investigates and compares the analytical properties of a series of applied
      conductive coatings for low-flow electrospray ionization developed in this
      laboratory vs. commercially-available types. Evaporated graphite is thoroughly
      compared with commercially available polyaniline (PANI) coated emitters and metal
      coated emitters. Each set of emitters was investigated to determine various
      performance characteristics, including susceptibility to electrical discharge in
      both positive and negative ionization modes, as well as emitter reproducibility
      and generation of a standard curve to determine each emitter coating's limit of
      detection and limit of quantitation. Furthermore, evaporated graphite and
      polyaniline coated fused silica capillaries were investigated to determine which
      coating is more stable over long-term analyses and during electrical discharge.

PMID- 16568173
TI  - Direct monitoring of toxic compounds in air using a portable mass spectrometer.
AB  - A portable tandem mass spectrometer, capable of performing atmospheric pressure
      chemical ionization (APCI) using a direct atmospheric inlet, is applied to the
      real-time monitoring of toxic compounds in air. Analytes of interest include
      dimethyl methylphosphonate, arsine, benzene, toluene, pyridine and vinyl acetate.
      The detection, identification and quantification of organic and inorganic
      compounds in air is demonstrated using short analysis times (<5 seconds) with
      detection limits in the low ppb (v/v) levels and linear dynamic ranges of several
      orders of magnitude. Highly specific detection and identification is achieved,
      even when the analyte is a trace component in a complex mixture including such
      interferents as fuels, lubricants, and cleaners. The effects of environmental
      conditions, including temperature and humidity, are delineated. Receiver
      operating characteristic (ROC) curves are presented to show the trade-off between
      false positive and false negative detection rates. Tandem mass spectrometry based
      both on collision-induced dissociation and on selective atmospheric pressure
      ion/molecule reactions is also used to increase selectivity and sensitivity.

PMID- 16568174
TI  - Surface-enhanced Raman spectroscopy of half-mustard agent.
AB  - The detection and identification of chemical warfare agents is an important
      analytical goal. Herein, it is demonstrated that 2-chloroethyl ethyl sulfide
      (half-mustard, CEES) can be successfully analysed using surface-enhanced Raman
      spectroscopy (SERS). A critical component in this detection system is the
      fabrication of a robust, yet highly enhancing, sensor surface. Recent advances in
      substrate fabrication and in the fundamental understanding of the SERS phenomenon
      enable the development of improved substrates for practical SERS applications.

PMID- 16568175
TI  - Development and optimization of a lab-on-a-chip device for the measurement of
      trace nitrogen dioxide gas in the atmosphere.
AB  - We propose the use of lab-on-a-chip technology for measuring gaseous chemical
      pollutants, and describe the development of a microchip for the detection of
      nitrogen dioxide (NO2) in air. A microchip fabricated from quartz glass has been
      developed for handling the following three functions, gas absorption, chemical
      reaction and fluorescence detection. Channels constructed in the microchip were
      covered with porous glass plates, allowing nitrogen dioxide to penetrate into the
      triethanolamine (TEA) flowing within the microchannel beneath. The nitrogen
      dioxide was then mixed with TEA and reacted with a suitable fluorescence reagent
      in the chemical reaction chamber in the microchip. The reacted solution was then
      allowed to flow into the fluorescence detection area to be excited by an
      ultraviolet light-emitting diode (UV-LED), and the fluorescence was detected
      using a photomultiplier tube (PMT). The reaction time, reagent concentration, pH,
      flow rate and other measurement conditions were optimised for analysis of
      nitrogen dioxide in air. Preliminary studies with standardized test solutions
      revealed quantitative measurements of nitrite ion (NO2-), which corresponded to
      atmospheric nitrogen dioxide in the range of 10-80 ppbv.

PMID- 16568177
TI  - TXRF analysis of aged three way catalysts.
AB  - A methodology for the quantitative analysis of the elements present in car
      exhaust catalysts by TXRF is described. Some of the most relevant catalytic
      components (Zr, Rh, Pd) and contaminant elements (P, Pb, Zn, Pt, Ca and Ni) on
      car Three Way Catalysts were quantified during vehicle aging. The study was
      conducted along the main axis of a Ford Focus 1.6i catalytic cartridge, aiming to
      obtain the axial profile of the elements retained or eliminated after more than
      59,000 km. The analysis of a fresh Three Way Catalysts (0 km) was also conducted
      for comparative purposes. The existence of a strong differences for elemental
      concentration in the interphase between the two blocks of the catalytic cartridge
      has been quantitatively measured for first time. In addition, the behaviour of
      the contaminant absorption capacity of both catalytic blocks has been obtained.
      Finally, the loss of the contaminant elements Pb and Zn to the environment has
      been proven.

PMID- 16568176
TI  - Analysis of gaseous toxic industrial compounds and chemical warfare agent
      simulants by atmospheric pressure ionization mass spectrometry.
AB  - The suitability of atmospheric pressure chemical ionization mass spectrometry as
      sensing instrumentation for the real-time monitoring of low levels of toxic
      compounds is assessed, especially with respect to public safety applications.
      Gaseous samples of nine toxic industrial compounds, NH3, H2S, Cl2, CS2, SO2,
      C2H4O, HBr, C6H6 and AsH3, and two chemical warfare agent simulants, dimethyl
      methylphosphonate (DMMP) and methyl salicylate (MeS), were studied. API-MS proves
      highly suited to this application, with speedy analysis times (<30 seconds), high
      sensitivity, high selectivity towards analytes, good precision, dynamic range and
      accuracy. Tandem MS methods were implemented in selected cases for improved
      selectivity, sensitivity, and limits of detection. Limits of detection in the
      parts-per-billion and parts-per-trillion range were achieved for this set of
      analytes. In all cases detection limits were well below the compounds'
      permissible exposure limits (PELs), even in the presence of added complex
      mixtures of alkanes. Linear responses, up to several orders of magnitude, were
      obtained over the concentration ranges studied (sub-ppb to ppm), with relative
      standard deviations less than 3%, regardless of the presence of alkane
      interferents. Receiver operating characteristic (ROC) curves are presented to
      show the performance trade-off between sensitivity, probability of correct
      detection, and false positive rate. A dynamic sample preparation system for the
      production of gas phase analyte concentrations ranging from 100 pptr to 100 ppm
      and capable of admixing gaseous matrix compounds and control of relative humidity
      and temperature is also described.

PMID- 16568178
TI  - Towards molecular imaging and treatment of disease with radionuclides: the role
      of inorganic chemistry.
AB  - Molecular imaging and radiotherapy using radionuclides is a rapidly expanding
      field of medicine and medical research. This article highlights the development
      of the role of inorganic chemistry in designing and producing the
      radiopharmaceuticals on which this interdisciplinary science depends.

PMID- 16568180
TI  - Development of a convenient new synthetic route to [3]ferrocenophanones.
AB  - [3]Ferrocenophanone rac-8 was prepared by several non-Friedel-Crafts pathways
      starting from a Mannich-type coupling of 1,1'-diacetylferrocene followed by
      catalytic hydrogenation. Hydride abstraction from the resulting alpha
      dimethylamino[3]ferrocenophane rac-14 with B(C6F5)3 followed by hydrolysis gave
      the ketone rac-8. Several variants of the Sommelet reaction, using
      ethylglyoxylate, formaldehyde or hexamethylenetetramine (urotropine) as the
      "oxidizing" reagent gave the alpha-[3]ferrocenophanone 8 in good to excellent
      yield. Some variants of these reactions were also used for the preparation of the
      pure enantiomer (R)-8. The electrochemical behaviour of 8 has been investigated
      and compared with related derivatives.

PMID- 16568179
TI  - Unsymmetrical surface modification of a heteropolyoxotungstate via in-situ
      generation of monomeric and dimeric copper(II) species.
AB  - Unsymmetrical functionalization of a discrete alpha-{SiW12O40} Keggin with two
      heterometallic building blocks, a Cu(II) dimer and a Cu(II) monomer, results in
      the formation of [{Cu2(O2CMe)2(5,5'-dimethyl-2,2'-bipy)2}{Cu(5,5'-dimethyl-2,2'
      bipy)2}SiW12O40] that displays interesting physical properties.

PMID- 16568181
TI  - Linear and star-shaped polynuclear Ru(II) complexes of 2-(2'
      pyridyl)benzimidazolyl derivatives: syntheses, photophysical properties and red
      light-emitting devices.
AB  - Two new star-shaped ligands with a 1,3,5-triphenylbenzene core, tmpb (1,3,5
      tris[p-2-(2'-pyridyl)benzimidazolylphenyl]benzene), and a 2,4,6-tris(p-biphenyl)
      1,3,5-triazine core, tmbt (2,4,6-tris[p-2-(2'-pyridyl)benzimidazolylbiphenyl]
      1,3,5-triazine), have been synthesized. Their corresponding trinuclear Ru(II)
      complexes [Ru3(tmpb)(bpy)6](PF6)6 (3) and [Ru3(tmpt)(bpy)6](PF6)6 (4) have been
      obtained. Two dinuclear linear Ru(II) complexes with previously reported ligands
      bmb (1,4-bis[2-(2'-pyridyl)benzimidazolyl]benzene) and bmbp (4,4'-bis[2-(2'
      pyridyl)benzimidazolyl]biphenyl) and formulae [Ru2(bmb)(bpy)4](PF6)4 (1) and
      [Ru2(bmbp)(bpy)4](PF6)4 (2) have also been synthesized. Photophysical and
      electrochemical properties of the new compounds have been investigated. All four
      compounds display a characteristic metal-to-ligand-charge transfer (MLCT)
      absorption band and emit a red light when excited at the maximum of the MLCT band
      with emission maximum at 624, 629, 623 and 625 nm, respectively in neat films at
      ambient temperature. The emission quantum efficiency of the four complexes in
      neat films was determined to be 0.15, 0.17, 0.04 and 0.05, respectively. Light
      emitting devices based on these four compounds were fabricated by spin-casting
      the compound as a neat film to an ITO substrate, followed by the deposition of an
      aluminium metal layer. All devices emit a deep red light and the device behavior
      resembles that of a light emitting electrochemical cell. The EL maximum of the
      devices 1, 2, 3, and 4 is at 637, 657, 678, and 655 nm, respectively. All four
      devices have a fast response time when a sufficiently high voltage is applied.
      The device based on 2 is the brightest with a maximum luminance of 133 cd m(-2)
      at 7 V. The performance of devices based on 1, 2, and 4 is in general much more
      efficient than the device based on [Ru(bpy)3](PF6)2, which was fabricated and
      evaluated under the same experimental conditions as for the devices based on 1-4.

PMID- 16568182
TI  - Fullerene bridged metallocyclodextrin donor-acceptor complexes: optical
      spectroscopy and photophysics.
AB  - Two pyridine substituted beta-cyclodextrins have been synthesized and coordinated
      to the photoactive metal centres, [Ru(II)(bpy)2] and [Re(I)(CO)3bpy], where bpy
      is 2,2'-bipyridyl. The photophysical and electrochemical properties of these
      model complexes have been examined and compared with dinuclear complexes formed
      when C60 was included between two cyclodextrin cavities of the
      metallocyclodextrin units. On inclusion of C60, significant quenching of the
      emission of the luminophores is observed. Concentration and laser power
      dependence confirm that this quenching is intramolecular. The quenching process
      is interpreted in terms of a photoinduced electron transfer between the
      photosensitizer and C60 centre on the basis of spectroscopic and electrochemical
      evidence. Rate constants of 1.3 +/- 0.1 x 10(8) and 7.0 +/- 0.4 x 10(7) s(-1)
      have been determined for the Ru and Re based complexes, respectively.
      Significantly, these large rate constants indicate that that there is substantial
      electronic communication across the cyclodextrin at least for excited state
      processes.

PMID- 16568183
TI  - Preparation and characterization of Cr(III), Mn(II), Fe(II), Co(II) and Ni(II)
      complexes of a hexaazadithiophenolate macrocycle.
AB  - The ligating properties of the 24-membered macrocyclic dinucleating
      hexaazadithiophenolate ligand (L(Me))2- towards the transition metal ions Cr(II),
      Mn(II), Fe(II), Co(II), Ni(II) and Zn(II) have been examined. It is demonstrated
      that this ligand forms an isostructural series of bioctahedral
      [(L(Me))M(II)2(OAc)]+ complexes with Mn(II) (2), Fe(II) (3), Co(II) (4), Ni(II)
      (5) and Zn(II) (6). The reaction of (L(Me))2- with two equivalents of CrCl2 and
      NaOAc followed by air-oxidation produced the complex [(L(Me))Cr(III)H2(OAc)]2+
      (1), which is the first example for a mononuclear complex of (L(Me))2-. Complexes
      2-6 contain a central N3M(II)(mu-SR)2(mu-OAc)M(II)N3 core with an exogenous
      acetate bridge. The Cr(III) ion in is bonded to three N and two S atoms of
      (L(Me))2- and an O atom of a monodentate acetate coligand. In 2-6 there is a
      consistent decrease in the deviations of the bond angles from the ideal
      octahedral values such that the coordination polyhedra in the dinickel complex 5
      are more regular than in the dimanganese compound 2. The temperature dependent
      magnetic susceptibility measurements reveal the magnetic exchange interactions in
      the [(L(Me))M(II)2(OAc)]+ cations to be relatively weak. Intramolecular
      antiferromagnetic exchange interactions are present in the Mn(II)2, Fe(II)2 and
      Co(II)2 complexes where J = -5.1, -10.6 and approximately -2.0 cm(-1) (H = 
      2JS1S2). In contrast, in the dinickel complex 5 a ferromagnetic exchange
      interaction is present with J = +6.4 cm(-1). An explanation for this difference
      is qualitatively discussed in terms of the bonding differences.

PMID- 16568184
TI  - Triazenide-bridged rhodium-palladium complexes: [I2Rh(mu-p-MeC6H4NNNC6H4Me
      p)2Pd(eta(3)-C3H5)]-, a stable paramagnetic [RhPd]4+ species with a localised
      Rh(II) centre.
AB  - Deprotonation of mixtures of the triazene complexes [RhCl(CO)2(p-MeC6H4NNNHC6H4Me
      p)] and [PdCl(eta(3)-C3H5)(p-MeC6H4NNNHC6H4Me-p)] or [PdCl2(PPh3)(p
      MeC6H4NNNHC6H4Me-p)] with NEt3 gives the structurally characterised
      heterobinuclear triazenide-bridged species [(OC)2Rh(mu-p-MeC6H4NNNC6H4Me
      p)2PdLL'] {LL' = eta(3)-C3H5 1 or Cl(PPh3) 2} which, in the presence of Me3NO,
      react with [NBu(n)4]I, [NBu(n)4]Br, [PPN]Cl or [NBu(n)4]NCS to give [(OC)XRh(mu-p
      MeC6H4NNNC6H4Me-p)2PdCl(PPh3)]- (X = I 3-, Br 4-, Cl 5- or NCS 6-) and
      [NBu(n)4][(OC)XRh(mu-p-MeC6H4NNNC6H4Me-p)2Pd(eta(3)-C3H5)], (X = I 7- or Br 8-).
      The allyl complexes 7- and 8- undergo one-electron oxidation to the corresponding
      unstable neutral complexes 7 and 8 but, in the presence of the appropriate
      halide, oxidative substitution results in the stable paramagnetic complexes
      [NBu(n)4][X2Rh(mu-p-MeC6H4NNNC6H4Me-p)2Pd(eta(3)-C3H5)], (X = I 9- or Br 10-). X
      Ray structural (9-), DFT and EPR spectroscopic studies are consistent with the
      unpaired electron of 9- and 10- localised primarily on the Rh(II) centre of the
      [RhPd]4+ core, which is susceptible to oxygen coordination at low temperature to
      give Rh(III)-bound superoxide.

PMID- 16568185
TI  - Ligating properties of a potentially tetradentate Schiff base
      [(CH3)2NCH2CH2N=CHC6H3(OH)(OMe)] with zinc(II), cadmium(II), cobalt(II),
      cobalt(III) and manganese(III) ions: synthesis and structural studies.
AB  - A series of Zn(II), Cd(II), Co(II), Co(III) and Mn(III) complexes with the Schiff
      base [(CH3)2NCH2CH2N=CHC6H3(OH)(OMe)], LH, derived from 2-dimethylaminoethylamine
      and o-vanillin, has been synthesised and structures of all the products have been
      established by X-ray crystallography. In the cases of zinc and cadmium, dimeric
      complexes [Zn(LH)2(NCS)] [Zn2(L)(mu(1,1)-CH3COO)(NCS)3] (1), [Cd2(L)2(Cl)2] (2)
      and [Cd2(L)2(NCS)2] (3), and for cobalt and manganese, monomeric complexes
      [Co(LH)2(NCS)]2 [Co(NCS)4] (4), [Co(LH)2(NCS)]ClO4 (5), [Co(L)(N3)(o
      vanillinate)] x 0.5 MeOH (6) and [Mn(LH)2(MeOH)2](ClO4)3 (7), are formed with
      various terminal ligands. All the complexes have been characterised by elemental
      analysis and IR spectra. UV-Vis and NMR spectroscopy, magnetic, and
      electrochemical studies, were also carried out where feasible. The Schiff base
      functions as a bi-, tri- or tetra-dentate chelating agent and coordinates via the
      protonated or deprotonated phenolic oxygen, amine and imine nitrogens, and only
      in case of 1 with the methoxy oxygen atoms, to the metal ion leading to the
      formation of mono- or bi-metallic complexes.

PMID- 16568186
TI  - The influence of N-substitution on the reductive elimination behaviour of
      hydrocarbyl-palladium-carbene complexes--a DFT study.
AB  - The reductive elimination of 2-hydrocarbyl-imidazolium salts from hydrocarbyl
      palladium complexes bearing N-heterocyclic carbene (NHC) ligands represents an
      important deactivation route for catalysts of this type. We have explored the
      influence that carbene N-substituents have on both the activation energy and the
      overall thermodynamics of the reductive elimination reaction using density
      functional theory (DFT). Given the proximity of the N-substituent to the three
      centred transition structure, steric bulk has little influence on the activation
      barrier and it is electronic factors that dominate the barriers' magnitude.
      Increased electron donation from the departing NHC ligand acts to stabilise the
      associated complex against reductive elimination, with stability following the
      trend: Cl < H < Ph < Me < Cy < iPr < neopentyl < tBu. The intimate involvement of
      the carbene p pi-orbital in determining the barrier to reductive elimination
      means N-substituents that are capable of removing pi-density (e.g. phenyl) act to
      promote a more facile reductive elimination.

PMID- 16568187
TI  - B(C6F5)3 adducts of transition metal acyl compounds.
AB  - The transition metal acyl compounds [Co(L)(CO)3(COMe)] (L = PMe3, PPhMe2, P(4-Me
      C6H4)3, PPh3 and P(4-F-C6H4)3), [Mn(CO)5(COMe)] and [Mo(PPh3)(eta(5)
      C5H5)(CO)2(COMe)] react with B(C6F5)3 to form the adducts
      [Co(L)(CO)3(C{OB(C6F5)3}Me)] (L = PMe3, 1, PPhMe2, 2, P(4-Me-C6H4)3, 3, PPh3, 4,
      P(4-F-C6H4)3), 5, [Mn(CO)5(C{OB(C6F5)3}Me)] 6 and [Mo(eta(5)
      C5H5)(PPh3)(CO)2(C{OB(C6F5)3}Me)], 7. Addition of B(C6F5)3 to a cooled solution
      of [Mo(eta(5)-C5H5)(CO)3(Me)], under an atmosphere of CO gave [Mo(eta(5)
      C5H5)(CO)3(C{OB(C6F5)3}Me)] 8. In the presence of adventitious water, the
      compound [Co{HOB(C6F5)3}2{OP(4-F-C6H4)3}2] 9, was formed from [Co(P(4-F
      C6H4)3)(CO)3(C{OB(C6F5)3}Me)]. The compounds 4 and 9 have been structurally
      characterised. The use of B(C6F5)3 as a catalyst for the CO-induced migratory
      insertion reaction in the transition metal alkyl compounds [Co(PPh3)(CO)3(Me)],
      [Mn(CO)5(Me)], [Mo(eta(5)-C5H5)(CO)3(Me)] and [Fe(eta(5)-C5H5)(CO)2(Me)] has been
      investigated.

PMID- 16568188
TI  - The electronic structure and spectra of spin-triplet ground state
      bis(biuretato)cobalt(III) coordination compounds.
AB  - The planar coordination compounds of cobalt(III) with bis(biuretato) ligands are
      highly unusual due to their intermediate spin triplet ground state. Density
      functional theory (DFT) and time-dependent DFT have been applied in a study of
      the structure and electronic spectroscopy of this type of coordination compounds.
      The investigations included prediction and spectroscopic measurements of the
      absorption and circular dichroism (CD), as well as an experimental study of the
      magnetic CD. The results obtained by TD-DFT were in excellent agreement with the
      observed spectral features, both regarding the d-d and the charge transfer
      regions. There was noted a systematic blue-shift of the TD-DFT results compared
      to experiment, corresponding to an offset of ca. 0.5 microm(-1) and a scaling
      factor of 1.25 for the transition energies. The DFT results are rationalized in
      terms of a qualitative MO analysis.

PMID- 16568189
TI  - Syntheses of copper(I)cis-1,3,5-tri-iminocyclohexane complexes.
AB  - Copper(I) complexes of the ligand cis-1,3,5-tris(cinnamylideneamino)cyclohexane
      (L) have been prepared from a versatile precursor complex, [Cu(I)(L)NCMe]BF4,
      which incorporates a labile acetonitrile ligand that can be exchanged to give a
      range of new Cu(L)X complexes (where X = Cl, Br, NO2, SPh). 1H NMR spectra and X
      ray structures of the Cl, Br and NO2 complexes show L coordinated in a symmetric
      fashion about the copper centre. The complexes have been further characterised
      using UV/Visible spectroscopy and cyclic voltammetry. CuLCl shows an
      electrochemically reversible Cu(I/II) redox couple at 0.51 V (vs. Ag/AgCl) while
      the CuLNO2 complex shows an analogous quasi-reversible wave at 0.41 V (vs.
      Ag/AgCl).

PMID- 16568190
TI  - Redox behavior of tumor-inhibiting ruthenium(III) complexes and effects of
      physiological reductants on their binding to GMP.
AB  - Biotransformation of ruthenium(III) anticancer complexes as hypothesized in the
      activation-by-reduction theory is the central topic of the present paper. The
      redox behavior of tetrachlorobis(azole)ruthenate(III)-type complexes was studied
      by NMR spectroscopy and square wave voltammetry. The influence of reducing agents
      on the binding behavior toward the DNA-modeling nucleotide GMP was determined by
      capillary electrophoresis, accompanied by identification of arising peaks by
      online coupling to electrospray ionization mass spectrometry. The determination
      of redox potentials revealed that the biologically relevant reductants ascorbic
      acid and glutathione are capable of reducing the studied Ru(III) complexes under
      physiological conditions. Characteristic differences in reduction kinetics
      dependent on the pH value can be explained by higher reduction strength of
      ascorbic acid and glutathione at higher pH compared to the pH-independent redox
      response of ruthenium(III) complexes. Binding behavior of (H2ind)[trans
      RuCl4(Hind)2] (Hind = 1H-indazole) toward GMP was found to be increased upon
      addition of two equivalents of glutathione but not of ascorbic acid. In contrast,
      only a minor influence on the GMP-binding under reductive conditions was found
      for (H2im)[trans-RuCl4(Him)2] (KP418, Him = 1H-imidazole).

PMID- 16568191
TI  - Synthesis, luminescence and ion-binding properties of palladium(II) complexes
      with 1,2-bis[di(benzo-15-crown-5)phosphino]ethane (dbcpe).
AB  - A series of palladium(II) complexes with 1,2-bis[di(benzo-15-crown
      5)phosphino]ethane ligand (dbcpe), [Pd(dbcpe)X2] (X = Cl 1, Br 2 and I 3), have
      been successfully synthesised and characterised. The X-ray crystal structure of
      dbcpe has also been determined. The cation-binding properties of the complexes
      have been studied and the stability constants with alkali metal cations
      determined. The crown-free analogue of dbcpe, 1,2-bis[bis(3,4
      dimethoxyphenyl)phosphino]ethane (ddmppe), and the related complexes have also
      been prepared and comparison studies have been made.

PMID- 16568192
TI  - Approach to undifferentiated chest pain in the emergency department: a review of
      recent medical literature and published practice guidelines.
AB  - Chest pain is the presenting complaint in over 6 million emergency department
      visits each year. Differentiating acute coronary syndrome (ACS) from other,
      noncardiac causes of chest pain is imperative in emergency practice. This article
      reviews the current medical evidence and published guidelines for the diagnosis
      of undifferentiated chest pain. A MEDLINE database search was conducted for
      relevant English language articles discussing an approach to undifferentiated
      chest pain. The published guidelines of the American College of Emergency
      Physicians, the American Heart Association, and the American College of
      Cardiology were also reviewed. The data surveyed suggest that, for all adult
      patients complaining of nontraumatic chest pain, a cardiac etiology for their
      presentation should be considered. History, physical examination,
      electrocardiogram, chest radiography, and to a lesser extent laboratory results
      can help differentiate ACS from other emergent diagnoses, e.g., aortic
      dissection, esophageal rupture, pulmonary embolus, pneumothorax, pneumonia, and
      pericarditis. No single feature of a patient's history, physical examination, or
      diagnostic test results can diagnose ACS to the exclusion of other causes of
      chest pain. Consequently, patients presenting with a complaint of chest pain
      frequently require serial evaluations, and admission to an observation unit or
      the hospital.

PMID- 16568193
TI  - Acute decompensated heart failure: formulating an evidence-based approach to
      diagnosis and treatment (part I).
AB  - Heart failure is a disease that effects affects approximately 5 million
      Americans, accounts for 1 million hospitalizations annually, and represents the
      most common hospital discharge diagnosis for patients over the age of 65. Despite
      the significant impact of this disease, the accepted approach to treatment of
      acute decompensated heart failure (ADHF) has changed little in over 40 years.
      Another potential problem is that differentiating ADHF from other causes of
      dyspnea can be difficult, as historical elements, physical examination findings,
      and radiographic results lack adequate sensitivities to accurately identify the
      disease. This article, the first of a two-part series, will explore the
      historically accepted disease models for heart failure and their relevance to
      developing a therapeutic approach to ADHF. Additionally, diagnostic issues in
      heart failure will be examined, particularly the emerging role of natriuretic
      peptide assays for the identification of ADHF.

PMID- 16568195
TI  - New diagnostic and treatment modalities for pulmonary embolism: one path through
      the confusion.
AB  - Pulmonary embolism is one of the greatest diagnostic challenges in emergency
      medicine. New techniques and strategies constantly arise for the diagnosis and
      treatment of this disease. A review of the new diagnostic and treatment
      modalities for pulmonary embolism (PE) suggests that it should be suspected in
      any patient with unexplained dyspnea, tachypnea, or chest pain. All patients
      suspected of PE must be risk stratified, ideally with a criteria-validated
      clinical decision rule. After assessing pre-test probability, D-dimer assays will
      reliably exclude PE in the low risk group and no further imaging is warranted.
      Computed tomography (CT) angiogram is the initial imaging study of choice for
      stable patients. V/Q scans should be used only when CT is not available or if the
      patient has a contraindication to CT scans or intravenous contrast. Bedside
      echocardiography or stabilization of the patient and CT angiogram are the initial
      tests for suspected massive PE. If PE is confirmed, hypotensive patients should
      be treated with thrombolytics. Both heparin and low molecular weight heparin are
      equally effective initial treatments for stable patients with suspected or
      confirmed PE. Because accurate screening and identification of pulmonary embolism
      frequently requires more than a single test, knowledge of existing diagnostic
      techniques allows an evidence-based strategy for diagnosis. New therapeutic
      choices may benefit patients with confirmed pulmonary embolism.

PMID- 16568194
TI  - Acute decompensated heart failure: formulating an evidence-based approach to
      diagnosis and treatment (part II).
AB  - Acute decompensated heart failure (ADHF) is a disease of enormous scope and
      impact. Despite significant advances in our understanding of the pathophysiology
      of the disease, the initial treatment of ADHF has changed little in the past 40
      years. This article, the second in a two-part series, will examine the emergency
      department approach to ADHF, including the issues of risk stratification and goal
      directed therapy. It will also review therapeutic interventions, including
      available medications and the role of non-invasive ventilation devices for the
      stabilization and treatment of ADHF.

PMID- 16568196
TI  - Blunt cardiac injury.
AB  - The diagnosis and management of blunt cardiac injury, formerly known as
      myocardial contusion, has challenged clinicians for decades. Caused primarily by
      motor vehicle collisions, significant blunt cardiac injury carries a high
      mortality rate. Yet no reliable diagnostic test exists to identify those patients
      at greatest risk for an adverse outcome. A literature search using the MEDLINE
      database was performed to compose a review of epidemiology, diagnostic
      intervention, and therapeutic approach. The results of the search indicate that,
      along with a high index of suspicion, utilizing a combination of
      electrocardiogram, troponin, and echocardiography for appropriate patients may
      improve the diagnosis, risk stratification and disposition of patients sustaining
      blunt cardiac injury.

PMID- 16568197
TI  - Patient noncompliance: causes and solutions.
AB  - This essay examines the subject of patient noncompliance with prescribed
      medications or other health regimens and its possible causes, and discusses
      possible solutions. Noncompliance or nonadherence to prescribed medical regimens
      may have serious detrimental effects on the patient's health and quality of life,
      and may lead to further morbidity or mortality. Proposed solutions to the problem
      of noncompliance are many (Table 3). If aggressively pursued, they may help
      improve the health of individual patients and the general community.

PMID- 16568198
TI  - The effects of the prophylactic tropisetron-propofol combination on postoperative
      nausea and vomiting in patients undergoing thyroidectomy under desflurane
      anesthesia.
AB  - PURPOSE: To evaluate the efficacies of tropisetron and tropisetron-propofol
      combination in the prophylaxis for postoperative nausea and vomiting in patients
      undergoing thyroidectomy under desflurane anesthesia. (This combination has
      apparently not been previously investigated for this particular surgery and
      anesthesia.) METHODS: Prospective, randomized, double-blind study. One hundred
      five patients aged between 19 and 68 years were included in the study. Group T
      received 5 mg of tropisetron (tropisetron group. n=35), group TP (tropisetron
      propofol group, n=35) received 5 mg of tropisetron and 0.5 mg/kg of propofol and
      group P (placebo group, n=35) received saline, immediately after anesthesia
      induction. The anesthesia induction regimen was applied to all patients, and
      anesthesia was maintained with 5-7% desflurane and 66% N 2 O in O 2 . RESULTS:
      Group TP reported a lower incidence of postoperative nausea and vomiting (17%)
      than those in groups T and P (42.8% and 77%, respectively). The postoperative
      antiemetic requirements were significantly higher in the placebo group compared
      to the other two groups (p<0.05). CONCLUSION: The tropisetron-propofol
      combination is more effective than tropisetron alone in the prevention of
      postoperative nausea and vomiting after thyroidectomy.

PMID- 16568199
TI  - Essays in public health and preventive medicine.

PMID- 16568200
TI  - I matched, not for residency, but to save a life.

PMID- 16568202
TI  - Disease activity and 18F-FDG uptake in organising pneumonia: semi-quantitative
      evaluation using computed tomography and positron emission tomography.
AB  - PURPOSE: The present study was conducted to evaluate whether( 18)F
      fluorodeoxyglucose positron emission tomography (FDG-PET) in combination with
      computed tomography (CT) reflects disease activity in patients with organising
      pneumonia. METHODS: Eighty-eight subjects who were normal (n=66) or who had
      proven organising pneumonia (n=22) underwent FDG-PET and CT imaging. The subjects
      included 55 men and 33 women, ranging in age from 24 to 63 years (mean 47 years).
      PET and CT data sets were digitally fused using a conformational PET/CT fusion
      algorithm. All scans were evaluated independently by two chest radiologists who
      were unaware of other clinical data. The visual score, maximal and mean
      standardised uptake value (SUV), and maximal and mean lesion-to-normal tissue
      ratio (LNR) were calculated. The imaging results were compared with the
      laboratory and pulmonary function test results. The inflammatory cells in the
      lesions were quantified immunohistochemically. RESULTS: The visual score, maximal
      and mean SUV, and maximal and mean LNR of the patients with organising pneumonia
      were significantly higher than those of the normal subjects. The patients with
      air-space consolidation had a significantly higher SUV than those without air
      space consolidation (mean+/-SD 3.08+/-0.39 vs 2.35+/-0.56; p<0.05). The number of
      CD45(+) cells was positively correlated with the maximal SUV (r=0.632, p<0.01)
      and the maximal LNR (r=0.453, p<0.05). The number of CD8(+) T lymphocytes also
      showed positive correlations with the maximal SUV (r=0.540, p<0.01) and the
      maximal LNR (r=0.547, p<0.01). CONCLUSION: Patients with organising pneumonia
      have an enhanced FDG accumulation which reflects the degree of disease activity.

PMID- 16568204
TI  - Developing nuclear medicine in developing countries: IAEA's possible mission.

PMID- 16568203
TI  - [(99m)Tc]Demotate 2 in the detection of sst(2)-positive tumours: a preclinical
      comparison with [(111)In]DOTA-tate.
AB  - PURPOSE: The aim of this study was to evaluate [(99m)Tc]Demotate 2 ([(99m)Tc-N(4)
      (0-1),Asp(0),Tyr(3)]octreotate) as a candidate for in vivo imaging of sst(2)
      positive tumours and to compare it with [(111)In]DOTA-tate ([(111)In
      DOTA(0),Tyr(3)]octreotate). METHODS: Labelling of Demotate 2 with (99m)Tc was
      performed at room temperature using SnCl(2) as reductant in the presence of
      citrate at alkaline pH. Radiochemical analysis involved ITLC and HPLC methods.
      Peptide conjugate affinities for sst(2) were determined by receptor
      autoradiography on rat brain cortex sections using [DOTA(0),(125)I
      Tyr(3)]octreotate as the radioligand. The affinity profile of Demotate 2 for
      human sst(1)-sst(5) was studied by receptor autoradiography in cell preparations
      using the universal somatostatin radioligand [(125)I][Leu(8),(D:
      )Trp(22),Tyr(25)]somatostatin-28. The internalisation rates of [(99m)Tc]Demotate
      2 and [(111)In]DOTA-tate were compared in sst(2)-positive and -negative control
      cell lines. Biodistribution of radiopeptides was studied in male Lewis rats
      bearing CA20948 tumours. RESULTS: Peptide conjugates showed selectivity and a
      high affinity binding for sst(2) (Demotate 2 IC(50)=3.2 nM and DOTA-tate
      IC(50)=5.4 nM). [(99m)Tc]Demotate 2, like [(111)In]DOTA-tate, internalised
      rapidly in all sst(2)-positive cells tested, but not in sst(2)-negative control
      cells. After injection in CA20948 tumour-bearing rats both radiopeptides showed
      high and specific uptake in the sst(2)-positive organs and in the implanted
      tumour and rapid excretion from non-target tissues via the kidneys. CONCLUSION:
      [(99m)Tc]Demotate 2, similarly to the known sst(2)-targeting agent [(111)In]DOTA
      tate, showed promising biological qualities for application in the scintigraphy
      of sst(2)-positive tumours.

PMID- 16568205
TI  - [18F]FETO for adrenocortical PET imaging: a pilot study in healthy volunteers.
AB  - PURPOSE: Functional imaging of the adrenal cortex by means of PET may play an
      important clinical role. Recently, we presented the synthesis and first
      evaluation of a novel 11beta-hydroxylase inhibitor, [(18)F]FETO, in rats
      displaying high tracer accumulation in the adrenals. In this study, we aimed to
      investigate for the first time the potency of [(18)F]FETO as a PET tracer for the
      adrenal cortex in humans. METHODS: An average preparation yielded 1-2 GBq of
      [(18)F]FETO ready to use. Ten healthy volunteers aged 24-57 years (five male and
      five female) were included in the study. After i.v. administration of 365 MBq
      [(18)F]FETO (246-391 MBq), dynamic images were acquired in 2D standard mode in 14
      frames over 45 min. Afterwards, whole-body scanning was performed. In addition to
      visual interpretation, semi-quantitative analysis using standardised uptake
      values (SUVs) was conducted. RESULTS: [(18)F]FETO distribution was similar in all
      scanned volunteers. Visually, pronounced accumulation of [(18)F]FETO was found in
      the adrenals, whereas moderate uptake was observed-at least in some of the
      subjects-for liver, renal calices, gallbladder, stomach walls and pancreas.
      Kidney and bowels showed only faint uptake. Median SUVs for the right and left
      adrenal glands were 15.6 (10.0-28.6) and 15.7 (10.3-35.9), respectively. The
      reference tissue (liver) displayed a median SUV of 2.5 (2.2-4.6). CONCLUSION:
      [(18)F]FETO is a valuable tracer for adrenocortical PET imaging, combining the
      longer half-life of( 18)F with a high 11beta-hydroxylase selectivity. In
      accordance with our findings in rats, FETO PET revealed very high accumulation in
      the adrenal glands in healthy volunteers.

PMID- 16568206
TI  - Elevation of radiolabelled thymidine uptake in RIF-1 fibrosarcoma and HT29 colon
      adenocarcinoma cells after treatment with thymidylate synthase inhibitors.
AB  - PURPOSE: We recently showed an increase in tumour uptake of 2-[(11)C]thymidine in
      patients with gastrointestinal malignancies after thymidylate synthase (TS)
      inhibition. To understand the phenomenon in more detail, we investigated whether
      TS inhibition by different TS inhibitors leads to a dose- and time-dependent
      change in the uptake of radiolabelled thymidine, and whether radiotracer uptake
      is related to changes in cell viability resulting from treatment. METHODS: RIF-1
      and HT29 cells were treated with the TS inhibitors 5-fluorouracil (5-FU) and
      AG337 (nolatrexed dihydrochloride), as well as cisplatin as control. The cell
      viability and net accumulation of [(3)H]thymidine after a 1-h pulse was
      determined at different times after drug treatment. RESULTS: In both cell lines,
      [(3)H]thymidine uptake increased after a 2-h treatment with 5-FU, in a dose- and
      time-dependent manner. [(3)H]thymidine uptake decreased at 24 and 48 h post
      treatment. AG337 also produced a similar effect. In contrast to the TS
      inhibitors, cisplatin decreased [(3)H]thymidine uptake in RIF-1 and HT29 cells at
      all time points. Cell viability was compromised only after 24 h. CONCLUSION:
      Using two types of TS inhibitor, we have shown an increase in [(3)H]thymidine
      uptake, in a dose-dependent manner, a few hours after TS inhibition when the cell
      viability was not compromised. This effect was not seen with a non-TS inhibitor.
      These findings suggest that 2-[(11)C]thymidine positron emission tomography can
      be used to study TS inhibition in vivo at early time points when cell viability
      is not compromised and may therefore be helpful in the development of new TS
      inhibitors and in differentiating between patients with tumours sensitive to TS
      inhibitors and those unlikely to respond.

PMID- 16568207
TI  - Cubilin and megalin in radiation-induced renal injury with labelled somatostatin
      analogues: are we just dealing with the kidney?

PMID- 16568208
TI  - The influence of photon depth of interaction and non-collinear spread of
      annihilation photons on PET image spatial resolution.
AB  - PURPOSE: The quality of PET imaging is impaired by parallax errors. These errors
      produce misalignment between the projected location of the true origin of the
      annihilation event and the line of response determined by the coincidence
      detection system. Parallax errors are due to the varying depths of photon
      interaction (DOI) within the scintillator and the non-collinear (NC) emission of
      the annihilation photons. The aim of this work was to address the problems
      associated with the DOI and the NC spread of annihilation photons and to develop
      a quantitative model to assess their impact on image spatial resolution losses
      for various commonly used scintillators and PET geometries. METHODS: A
      theoretical model based on Monte Carlo simulations was developed to assess the
      relative influence of DOI and the NC spread of annihilation photons on PET
      spatial resolution for various scintillator materials (BGO, LSO, LuAP, GSO, NaI)
      and PET geometries. RESULTS: The results demonstrate good agreement between
      simulated, experimental and published overall spatial resolution for some
      commercial systems, with maximum differences around 1 mm in both 2D and 3D mode.
      The DOI introduces an impairment of non-stationary spatial resolution along the
      radial direction, which can be very severe at peripheral positions. As an
      example, the radial spatial resolution loss due to DOI increased from 1.3 mm at
      the centre to 6.7 mm at 20 cm from the centre of a BGO camera with a 412-mm
      radius in 2D mode. Including the NC, the corresponding losses were 3.0 mm at the
      centre and 7.3 mm 20 cm from the centre. CONCLUSION: Without a DOI detection
      technique, it seems difficult to improve PET spatial resolution and increase
      sensitivity by reducing the detector ring radius or by extending the detector in
      the axial direction. Much effort is expended on the design and configuration of
      smaller detector elements but more effort should be devoted to the DOI
      complexity.

PMID- 16568209
TI  - Incidence and patterns of neuraxis metastases in children with diffuse pontine
      glioma.
AB  - PURPOSE: We performed a retrospective study of patients with diffuse pontine
      glioma (DPG) who suffered neuraxis metastasis (NM) and characterized the
      incidence, clinical features, radiologic findings, and patterns of disease
      dissemination. METHODS: Magnetic resonance imaging (MRI) of brain and spine was
      used to assess NM. Some patients also underwent magnetic resonance spectroscopy
      (MRS) (6 patients) and fluorodeoxyglucose positron emission tomography (FDG-PET)
      scans (13 patients) to further evaluate areas of metastatic disease. Three
      patients had histologic confirmation of disease at the site of NM. RESULTS:
      Between 1986 and 2003, 18 of 96 patients (17.3%) with DPG developed NM. The
      median age at diagnosis was 8 years (range, 4-17). All patients had adjuvant
      chemotherapy and/or focal radiotherapy at diagnosis. The NM occurred at a median
      of 15 months from diagnosis of DPG (range, 3-96). Three patterns of NM were seen
      on MRI of brain and spine in these patients; 8 (39%) had parenchymal (PM), 4
      (22%) leptomeningeal (PM), 2 (11%) subependymal, and in 5 a combination of two or
      more patterns. The MRS and FDG-PET scan of suspected areas of metastatic disease
      was consistent with tumor in 6 of 6 and 12 of 13 patients who underwent these
      procedures respectively. Three patients also had histologic confirmation of
      malignant glioma at the site of NM. Despite salvage therapy, all 18 patients have
      died of disease at a median of 5 months (range, 0.5-20) from diagnosis of
      neuraxis spread. CONCLUSION: Our study emphasizes the need for screening patients
      with DPG for NM at the time of recurrence.

PMID- 16568211
TI  - Laser-induced autofluorescence study of caries model in vitro.
AB  - Laser-induced autofluorescence spectra of teeth irradiated by a 337 nm nitrogen
      laser were measured during in vitro caries formation through initial enamel
      demineralization and introducing of carious bacterial flora in the lesions
      developed. Spectra obtained from sound teeth consist of an intensive maximum at
      480-500 nm and secondary maximum at 430-450 nm. In the process of caries
      formation, we observed an increase in the intensity at 430-450 nm and the
      appearance of two maxima in the red spectral region-at 590-650 nm. The intensity
      increase at 430-450 nm was related to the tooth demineralization. Bacteria
      presence and their metabolism products induced an increase in the absorption in
      the UV-blue spectral region at 350-420 nm and the appearance of a fluorescence
      signal in the long-wave spectral region at 590-650 nm. From the point of view of
      tissue optics, these results allow caries to be considered as consisting of two
      different phenomena-tissue destruction and bacterial flora and its metabolism
      products increase. The results could be used to obtain a more complete picture of
      caries formation on the base of its fluorescent properties.

PMID- 16568210
TI  - Low-energy irradiation stimulates formation of osteoclast-like cells via RANK
      expression in vitro.
AB  - Low-energy laser irradiation (Ga-Al-As semiconductor laser, output 50 mW) was
      applied to rat osteoclast precursor cells for 1, 3, 6, or 10 min at 24-h
      intervals during the culture period. The number of tartrate-resistant acid
      phosphatase positive multinucleate cells was increased by approximately 1.3-fold
      in the 3- and 6-min irradiation groups. Further, osteoclasts appeared on day 2 in
      the laser irradiation groups but not until day 3 in the control groups. In
      immunohistochemical staining for receptor activator of NF-kappaB (RANK), the
      laser irradiation groups showed significantly greater amounts of staining in
      comparison with the control group on days 2 and 3. Reverse transcription
      polymerase chain reaction results also showed that the expressions of RANK were
      upregulated. In the pit formation assay, resorption pits were significantly more
      abundant in the laser irradiation groups than in the controls. The present
      results suggest that low-energy laser irradiation facilitates differentiation and
      activation of osteoclasts via RANK expression.

PMID- 16568212
TI  - WITHDRAWN: Validation of the Tunisian version of the rheumatoid arthritis quality
      of life (RAQoL) questionnaire.
AB  - Ahead of Print article withdrawn by publisher

PMID- 16568213
TI  - Double-filtration plasmapheresis for resolution of corticosteroid resistant adult
      onset Still's disease.
AB  - A 45-year-old Japanese male was diagnosed with adult onset Still's disease
      (AOSD). High-dose corticosteroid initially resolved the illness; however, high
      fever, maculopalpular rashes, arthralgia, and acute pericarditis rapidly
      recurred, and were followed by a somnolent state without focal signs. A diagnosis
      of corticosteroid resistant, severe, recurrent AOSD was made, and double
      filtration plasmapheresis (DFPP) was performed immediately. The somnolent state
      began to resolve during the first plasmapheresis procedure, and the other
      symptoms resolved shortly thereafter. DFPP theoretically removes monocyte
      activating cytokines, such as monocyte colony-stimulating factor (M-CSF) from the
      circulation, and therefore may prove to be an effective treatment for
      corticosteroid resistant, rapidly developing cases of AOSD.

PMID- 16568214
TI  - Complications associated with transobturator sling procedures.
AB  - This study aims to determine the complications associated with trans-obturator
      slings as reported to a national database. We required "MAUDE", a database that
      collects reports of complications associated with medical devices and which is
      maintained by the Food and Drug Administration. We searched for complications
      associated with three different, commercially available trans-obturator slings.
      We then tabulated the results by type of complication, by date of occurrence, and
      by type of sling. Between January 2004 and July 2005, 140 reports of 173
      complications associated with trans-obturator tapes were reported to the MAUDE
      database. Previously unreported injuries, such as obturator nerve injuries, large
      blood losses (>or=600cc), and ischiorectal fossa abscesses, were documented.
      Serious complications occur with the trans-obturator tape systems, but the rates
      are unknown due to database limitations. The type of complication appears to
      differ between devices and this may reflect different implantation systems and
      different polypropylene mesh formulations. Improved tracking of device
      complications is necessary to maximize patient safety.

PMID- 16568215
TI  - Postpartum urinary incontinence: a comparison of vaginal delivery, elective, and
      emergent cesarean section.
AB  - The aim of this study was to assess the impact of delivery on the pelvic floor
      and whether cesarean section (C/S) can prevent pelvic floor injury. Five hundred
      thirty nine women were divided into three groups according to the delivery method
      adopted: elective C/S, emergent C/S, and vaginal delivery. A urinary incontinence
      questionnaire survey was conducted around 1 year postpartum. Emergent C/S may be
      a major risk factor for postpartum urinary incontinence and interfere with the
      benefit of elective C/S for preventing pelvic floor injury. Hence, not all C/S
      deliveries can reduce the likelihood of postpartum urinary incontinence. The key
      lies in whether the C/S is performed before labor.

PMID- 16568216
TI  - Anatomy of the superficial temporal artery and its branches: its importance for
      surgery.
AB  - The temporoparietal, parieto-occipital flaps or the forehead flaps that are used
      in reconstructive surgery are prepared on the superficial temporal artery (STA)
      and its branches. For a successful surgery and a suitable flap design, adequate
      anatomical knowledge is needed. In our study, the red colored latex solution was
      injected into the external carotid artery; the STA and its branches were
      dissected in 27 specimens. The mean diameter of the STA at the zygomatic arch was
      determined as 2.73+/-0.51 mm. The diameters of the frontal branch were bigger
      than those of the parietal branch in 15 samples out of 27. The diameters of both
      the frontal and parietal branches were equal in four samples. The diameter of the
      parietal branch was bigger than that of the frontal branch in eight samples. In
      20 samples out of 27 (74.07%), the bifurcation point of the STA was above the
      arch. In six samples (22.22%), the STA bifurcated directly over the arch. In only
      one sample (3.70%), bifurcation was not observed and the STA continued only as a
      frontal branch (absence of the parietal branch). The absence of the frontal
      branch was not encountered. In one sample (3.70%), double parietal branches were
      observed. In six samples out of 27 (22.22%), zygomatico-orbital artery was not
      encountered. In 21 samples (77.77%), zygomatico-orbital arteries ran towards the
      face, parallel to zygomatic arch and distributed in the orbicularis oculi muscle.
      The transverse facial artery existed in all samples. The auricular branches
      running to the helix and tragus were observed in all samples. The STA was 16.68+/
      0.35 mm at the front of the tragus. Some landmarks were chosen on the head and
      then the STA was observed where it crossed all of these landmarks. This paper
      confirms the well-known variability of the superficial temporal arterial branches
      and their relation to the pericranial region. Knowledge concerning the arterial
      features of the lateral forehead region is important for the aesthetic surgeon.
      STA and its branches have been found to be suitable for use in microvascular
      anastomoses. A better understanding of the midline forehead vascularity should
      allow modification of reconstructive techniques and reduce postoperative
      complications.

PMID- 16568217
TI  - Neural symmetry and functional asymmetry of the mandible.
AB  - Even in the absence of malformation or skull base asymmetry, the mandible may be
      physiologically asymmetric and this remains a major challenge in the orthodontic
      treatment. The mandible is a bone formed by a primary subunit, i.e., the neural
      part, with different functional secondary subunits, so we suggest that in a
      normal mandible the asymmetry was caused by the secondary functional subunit and
      the neural part is nearly symmetric. Eighty-three dry human mandible samples were
      studied. The measurements of the size of the mandible (corpus, ramus, mandible
      notch, condylar process, the angle of the mandible) and the neural subunit (the
      mandibular canal and the position of the mental and mandibular foramina) were
      measured bilaterally. The left and right sides were compared according to the
      dental status: 60 dentate and 23 edentulous mandibles. The calculation of the
      symmetry was based on the paired Student t test, the absolute difference |R-L|
      and the relative absolute difference |R-L|/|R+L|x100. The mandibular canal and
      the position of the foramina were symmetric, except for the position of the
      mandibular foramen in relation to the mandible notch. The symmetry was not
      modified by the dental status. The total length of the mandible and the length of
      the ramus were greater on the left side independently from the dental status. The
      length of the corpus and the mandible angle were symmetric in each group. The
      mandible notch was always asymmetric and its height was greater in the dentate
      group. The condylar process was the most asymmetric structure in each group. The
      primary subunit of the mandible, surrounding the mandibular canal, is a symmetric
      component of the mandible and is not modified by the dental status. The angle of
      the mandible between the corpus and ramus is another symmetric parameter that is
      important for the facial architecture. The ramus and especially the mandibular
      notch as well as the condylar process are the most asymmetric subunits influenced
      by the functional matrices.

PMID- 16568218
TI  - Determination of dimensions and angles of mandible in the fetal period.
AB  - The aim of the present study was to determine the dimensions of the mandible
      during the fetal period, the relationship between the growth rates of the angle
      of the mandible and the dimensions of the mandible. Furthermore the angle of
      union of the two halves of the body of the mandible on the horizontal mandibular
      plane, which was not described elsewhere, is explored in this study. One hundred
      and sixty-one human fetuses (83 males and 78 females) without any cranio-facial
      or mandibular asymmetry, external pathology or anomaly and aged between 9 and 40
      weeks of gestation were used in the study. Cases were stratified into four groups
      according to their developmental ages, that is, first trimester, second
      trimester, third trimester, and term fetuses. Cranio-facial parameters in
      addition to bi-condylar, bi-gonial, bi-mental tubercular, condyle-gonion, gonion
      mental tubercle, condyle-mental tubercle, gonion-pogonion distances were
      measured. The degree of the angle of the mandible, angle of union of the two
      halves of the body of the mandible and sagittal length of the base of the
      mandible were calculated. The means of the parameters with respect to gestational
      weeks and groups were computed. While there were no sex differences in any of the
      parameters (P>0.05) there were very significant relationships between gestational
      age and parameters (P<0.001). The mean degree of the angle of the mandible during
      the fetal period was 122+/-8 degrees . The mean alpha angle of the base of the
      mandible was 65+/-8 degrees . None of these angles varied significantly
      throughout the fetal period. Height of the ramus of the mandible increased more
      than the length of the body of the mandible and bi-gonial distance in the first
      and second trimesters while in the third trimester and term period they increased
      at the same rate. Comparisons of groups for the ratio of the transverse to the
      sagittal lengths of the mandible revealed significant differences between first
      and second trimesters with term group (P<0.05). Accordingly, bi-gonial distance
      of the mandible increased more during the third trimester and term time than the
      first and second trimesters, compared with the sagittal length of the mandible.
      The morphometric features and architectural changes observed in the mandible do
      not totally occur during the fetal period but continue later in childhood and
      adulthood.

PMID- 16568219
TI  - Attitudes and reactions of Jordanian medical students to the dissecting room.
AB  - Emotional and psychological reactions of Jordanian medical students to the
      dissecting room (DR) were assessed. A questionnaire was distributed to 200
      students in preclinical years in the academic year 2002-2003 in the faculty of
      medicine at Jordan University of Science and Technology; 145 students have
      responded. Varying degree of fear on first entering the DR was reported by 28.4%.
      The most frequent reactions were recurring visual images of cadavers 28.9% and
      palpitation 19.3%. Students' reactions were most commonly elicited by smell of
      the DR 58.5% and by fear of infection 50.3%. The most frequent method of coping
      with such fears was by rationalization 89.8%. Significant gender differences
      (P<0.05) were found in the most aspects of DR experiences. Female students showed
      higher level of fear, reported recurring visual images of cadavers more often
      than males, were more disturbed by certain stimuli in the DR and used religious
      books and praying as coping methods more frequently than their male peers. The
      need for appropriate psychological preparation of students before DR practical on
      human cadavers is discussed.

PMID- 16568220
TI  - Factors predicting long-term responses to splenectomy in patients with idiopathic
      thrombocytopenic purpura.
AB  - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder
      for which appropriate diagnostic treatments are uncertain. The response to
      splenectomy varies from 60% to 90%, and the remaining patients relapse and
      require further treatment. Therefore, it is important to predict the outcome of
      splenectomy before and after surgery. The objective of this study was to evaluate
      the efficacy of splenectomy in patients diagnosed with ITP. MATERIALS AND
      METHODS: From 1988 to 2004, we splenectomized 32 patients with ITP; 17 underwent
      laparoscopic splenectomy (LS) and 15 underwent conventional open splenectomy
      (OS). For analysis, patients were separated retrospectively into two groups: the
      "responding group," those who showed good outcomes with splenectomy, and the "non
      responding group," those who did not show good outcomes with splenectomy. Blood
      samples were examined before and immediately after surgery (day 0) and on
      postoperative days (POD) 1, 3, 5, and 7. RESULTS: The median follow-up was 8.3
      years (range: 1-16 years). The overall 5- and 10-year survival rates after
      splenectomy were 96.9% (one death). The responding group included 24 patients
      (75%), and the non-responding group included 7 (21.9%). Platelet counts in the
      responding group increased gradually until POD 7, and although platelet counts in
      the non-responding group were almost constant until POD 5, they subsequently
      decreased until POD 7. Average platelet counts in the responding and non
      responding groups were 269 and 124 x 10(9)/l on POD 7, respectively (P < 0.05).
      The pre- to post-surgery ratio of platelet counts were almost the same as the
      result of the actual data. Platelet counts during the long-term follow-up for the
      responding and non-responding groups were related to those noted on discharge.
      CONCLUSIONS: A high platelet count on POD 7 was associated with a good response
      to splenectomy, but age at surgery, the time interval between diagnosis and
      splenectomy, and prior responses to corticosteroid were not. We suggest that long
      term outcomes of splenectomy can easily be predicted by platelet counts on POD 7.

PMID- 16568221
TI  - Peritoneal cytology does not increase the prognostic information provided by TNM
      in gastric cancer.
AB  - BACKGROUND: This study aimed at verifying whether peritoneal cytology could
      improve the prognostic information provided by TNM staging in gastric cancer
      patients. METHOD: The presence of free peritoneal tumor cells was investigated in
      168 patients who underwent curative resection for gastric cancer from January
      1992 to July 2002 in Verona, Italy. The influence of peritoneal cytology on
      survival was evaluated by a Cox regression model, controlling for potential
      confounders. RESULTS: Twenty-three patients (14%) had positive peritoneal
      cytology. Patients with positive lavage were more likely to present serosal
      infiltration (100 vs. 46%) and nodal metastases (91 vs. 67%; P < 0.001). Positive
      lavage was associated with a very poor prognosis: 3-year survival was only 9%
      (95% CI 2-27%) when peritoneal cancer cells had been detected, whereas survival
      reached 50% (95% CI 42-59%) in patients with a negative cytology. In multivariate
      survival analysis, peritoneal cytology was an independent predictor of mortality
      when controlling for sex, age, site, histology, and nodal metastases, but not
      when adjusting also for depth of tumor invasion (RR of positive versus negative =
      1.2, 95% CI 0.7-2.0). Similarly, the influence of peritoneal cytology on survival
      was no longer significant when univariate analysis was restricted to T3/T4
      patients (RR = 1.5, 0.9-2.5). CONCLUSIONS: Positive peritoneal cytology was a
      marker of poor prognosis in gastric cancer patients. Nevertheless, peritoneal
      lavage did not increase the prognostic information already provided by the TNM
      staging system in this Italian series.

PMID- 16568222
TI  - Re: "Highlights in surgery through outstanding ISS/SIC surgeons".

PMID- 16568223
TI  - The role of adrenal venous sampling in the surgical management of primary
      aldosteronism.
AB  - OBJECTIVE: Primary aldosteronism is the most common endocrine form of secondary
      hypertension, but no single test or imaging method always identifies it.
      Identification of a unilateral overproduction of aldosterone due to Conn's
      adenoma or unilateral hyperplasia is of utmost importance to the surgeon.
      MATERIALS AND METHODS: We reviewed our experience with primary aldosteronism in
      46 consecutive patients who had undergone adrenalectomy at the Surgical Pathology
      Institute, University of Padua since 1993. All the patients underwent a CT scan.
      Adrenal venous sampling was performed in those patients with negative or
      equivocal findings on imaging studies. RESULTS: Computed tomography was non
      contributory in 12 patients and frankly misleading in 2 patients, demonstrating a
      probable mass lesion in the contralateral but not in the ipsilateral adrenal.
      Eighteen patients had selective venous sampling that was successful in altering
      the management of 14 cases. Eleven patients who biochemically had an adrenal
      adenoma, had normal/equivocal CT, while the remaining 3 had bilateral or
      contralateral adrenal masses. Venous sampling localized aldosterone secretion and
      an adenoma, less than 1 cm in diameter, was removed, curing their hypertension.
      Eleven patients were treated by open adrenalectomy and 35 by the lateral
      transperitoneal laparoscopic approach. Histological examination revealed 45
      Conn's adenomas, of which 13 had a diameter of less than 1 cm (range 0.3-0.8),
      and 1 case of nodular hyperplasia. CONCLUSIONS: Patients who have equivocal or
      unexpected CT findings should proceed to hormonal localization. Adrenal venous
      sampling is essential in patients with equivocal CT scans to avoid unnecessary
      and inappropriate adrenalectomy.

PMID- 16568225
TI  - Surgery for "body packers"--a 15-year experience.
AB  - BACKGROUND: "Body packing" of illegal drugs has increased in the last decades,
      and with it our experience in treating these patients, yet no clear guidelines
      for surgical treatment are available. We examined the characteristics and
      outcomes of patients who required surgical intervention. STUDY DESIGN: Charts of
      all patients who underwent surgery at our institution for ingested drug packets
      between January 1990 and January 2005 were reviewed. Patients were identified by
      a pre-existing list of names collected prospectively and by admission codes.
      Reviewed parameters included presentation, method of diagnosis, indication for
      surgery, procedure, and patient outcome. RESULTS: Twenty-five patients were
      identified, for whom charts were available for review. Main indications for
      surgery were drug toxicity and small bowel obstruction. Most packets were
      retrieved using a combination of milking and multiple enterotomies. A high rate
      (40%) of postoperative wound infection was found. The incidence of wound
      infection correlated significantly with the number of enterotomies. CONCLUSION:
      Surgical intervention for body packing remains the treatment for a minority of
      these patients. Patients should be placed in lithotomy to facilitate the exposure
      of the entire gastrointestinal tract, and to allow milking of the packets and
      their possible retrieval through the anus. The number of enterotomies should be
      minimized in order to reduce the risk of wound infection. If multiple
      enterotomies are used, the surgeon should consider leaving the wound open for
      delayed closure.

PMID- 16568224
TI  - Outcomes of surgery for mid and distal rectal cancer in the elderly.
AB  - BACKGROUND: This study aimed to evaluate the surgical strategies, operative
      results, and oncological outcomes of elderly patients who underwent curative
      resection for mid and distal rectal cancer. Comparison was made with patients of
      younger age. STUDY DESIGN: Of the 612 patients who underwent curative resection
      for rectal cancer, 133 were older than 75 years of age. Comparisons were made
      between the young and elderly patients in the aspects of operative strategies,
      operative results, and long-term outcomes. RESULTS: Resection resulting in a
      permanent end colostomy was performed in 96 patients (15.7%), and there was no
      difference between young and elderly patients. There was a female predominance in
      the elderly group. Elderly patients also had a higher incidence of comorbid
      medical diseases, especially cardiovascular and neurological diseases. The
      operative time, blood loss, and incidence of intraoperative complications did not
      differ in the two groups. However, significantly fewer elderly patients underwent
      adjuvant radiation and/or chemotherapy. The overall 30-day mortality was 1.14%.
      There was no difference between the elderly patients and younger patients in
      hospital mortality (P = 0.178). The complication rates of the elderly and young
      patients were 36.8% and 30.1%, respectively (P = 0.141). Comparison between the
      individual complications in the elderly and young patients revealed significantly
      more cardiovascular complications in the elderly patients. With the median follow
      up of the surviving patients of 45.1 months, the overall 5-year survival of the
      elderly and younger groups was 47.7% and 70.1%, respectively (P < 0.001). The 5
      year cancer-specific survival was 75.4% and 67.5% in the young and elderly
      patients, respectively (P = 0.061). CONCLUSIONS: Curative resection for mid and
      distal rectal cancer for the elderly can be performed safely with the same
      strategies of sphincter preservation used for younger patients. The postoperative
      complications and the 5-year cancer-specific survival rates were similar to those
      of younger patients.

PMID- 16568227
TI  - Sequential preoperative ipsilateral portal and arterial embolization in patients
      with colorectal liver metastases.
AB  - BACKGROUND: Preoperative portal vein embolization (PVE) induces ipsilateral
      atrophy of the hepatic parenchyma to be resected, as well as contralateral
      compensatory hypertrophy of the residual liver. However, there are two potential
      problems with this technique: inadequate contralateral hypertrophy and tumor
      progression while waiting for the non-embolized liver to hypertrophy. We devised
      a strategy to deal with these two problems by performing an ipsilateral hepatic
      artery embolization 6 weeks after an unsatisfactory PVE in an effort to
      accelerate the hypertrophy of the remnant liver. MATERIALS AND METHODS: Two
      patients with colorectal liver metastases underwent to this sequential
      preoperative treatment in order to achieve resectability of their metastatic
      disease. RESULTS: Both patients successfully underwent major hepatic resection.
      CONCLUSIONS: In our experience sequential ipsilateral portal vein and hepatic
      artery embolization extended the indications for liver resection for metastatic
      colorectal cancer.

PMID- 16568226
TI  - Posttraumatic thromboprophylaxis revisited: an argument against the current
      methods of DVT and PE prophylaxis after injury.
AB  - BACKGROUND: Thromboprophylaxis after injury is a controversial issue. Practices
      and outcomes vary widely. METHODS: Review of selected trauma literature on venous
      thromboprophylaxis after injury. RESULTS: Multiple trauma articles suggest that
      the efficacy of different methods of thromboprophylaxis is unproven. Most of the
      practices on this issue are extrapolated from studies which were performed in non
      trauma patients and therefore, may not be applicable in the unique trauma
      population. CONCLUSIONS: In the absence of undisputable evidence, none of the
      current methods of venous thromboprophylaxis after injury should be considered as
      standard of care. There is a need to discover new methods of thromboprophylaxis
      for the Trauma patient.

PMID- 16568228
TI  - Indication of hepatopancreatoduodenectomy for biliary tract cancer.
AB  - BACKGROUND: The indication for a hepatopancreatoduodenectomy (HPD) in patients
      with advanced biliary tract cancer is still controversial, because this
      aggressive surgery might be associated with high mortality and morbidity rates.
      In this study, we review our experience with HPD for advanced biliary tract
      cancer, and seek to define the indication for HPD. METHODS: Eleven patients with
      biliary tract cancer underwent HPD at Wakayama Medical University Hospital
      between 1986 and 2004. Univariate analysis was used to assess independent
      variables of the mortality and morbidity associated with HPD. RESULTS: The rates
      of mortality and morbidity were 18% and 82%, respectively. Univariate analysis
      showed that the total serum bilirubin level before surgery and the hepatic
      parenchymal resection of more than two Healey's segments correlated significantly
      with an increased risk of severe complications (P = 0.044, 0.0152, respectively).
      The 1-, 2-, and 3-year survival rates were 44%, 33%, and 11%, respectively.
      CONCLUSIONS: Hepatopancreatoduodenectomy might offer a chance of long survival by
      yielding a tumor-free margin in selected patients who are able to tolerate such
      an aggressive operation, but the indication for this aggressive surgery should be
      carefully considered.

PMID- 16568229
TI  - Atherosclerosis may be caused by inadequate levels of turbulence and mixing.

PMID- 16568230
TI  - Total colectomy improves altered distribution of regulatory T cells in patients
      with ulcerative colitis.
AB  - BACKGROUND: It is now generally believed that regulatory T cells (Tregs) play an
      important role in peripheral tolerance, and a defect in Tregs is considered one
      of the most important factors in the induction of various kinds of autoimmune
      disease including ulcerative colitis (UC). Here, we examined the change in
      frequency of Tregs phenotype in five patients with UC whose condition had not
      been controllable by conventional conservative therapy and who were scheduled for
      total colectomy. AIMS: The aim of this study was to elucidate the role of Tregs
      in the pathogenesis of UC in a clinical setting. METHODS: Peripheral blood
      mononuclear cells (PBMCs) were obtained from five patients with UC, and the
      change in frequency of Tregs was analyzed by flow cytometry before total
      colectomy and on postoperative days 1, 7, and 20. Tregs were defined as CD4+
      CD25+ CD45RA+ T cells, and data (%) were expressed as frequency of Tregs/CD4+ T
      cells. Peripheral blood mononuclear cells (PBMCs) from healthy blood donors (n =
      5) and from patients undergoing other types of major surgery (n = 5) were used as
      controls. RESULTS: Comparison with normal subjects showed that generation of
      Tregs was suppressed in UC patients before they underwent total colectomy (0.95
      versus 5.06; P = 0.009). The frequency of Tregs increased shortly after total
      colectomy. The frequency at postoperative days 1, 7, and 20 was 3.81%, 8.13%, and
      3.76%, respectively. There were significant differences in the change in
      frequency in the period before surgery and postoperative day 1, between
      postoperative days 1 and 7, and between days 7 and 20. CONCLUSIONS: Elimination
      of targeted antigens residing in the colorectal mucosa by total colectomy
      improved the suppressed distribution of Tregs in UC patients. The present study
      provides the first direct clinical evidence that Tregs play a pivotal role in the
      pathogenesis of UC.

PMID- 16568232
TI  - Impact of overweight and pneumoperitoneum on hemodynamics and oxygenation during
      prolonged laparoscopic surgery.
AB  - BACKGROUND: Anesthesia adversely affects respiratory function and hemodynamics in
      obese patients. Although many studies have been performed in morbidly obese
      patients, data are limited concerning overweight patients [BMI 25-29.9 kg m(-2)].
      The aim of this study was to evaluate the effects of prolonged pneumoperitoneum
      in Trendelenburg position on hemodynamics and gas exchange in normal and
      overweight patients. METHODS: We studied 15 overweight and 15 non-obese [BMI 18.5
      24.9 kg m(-2)] patients who underwent totally endoscopic robot-assisted radical
      prostatectomy under general anesthesia with an inspired oxygen fraction of 0.5. A
      standardized anesthetic regimen was used, and patients were examined at standard
      times: after induction of anesthesia and Trendelenburg posture, every 30 minutes
      after establishing pneumoperitoneum, and after the release of the
      pneumoperitoneum with the patient still in Trendelenburg position. RESULTS: After
      induction of anesthesia and Trendelenburg positioning arterial oxygen pressure
      [P(a)O2] and alveolar-arterial difference in oxygen tension [A(a)DO2] differed
      significantly between both groups with lower P(a)O2 [235 +/- 27 versus 164 +/- 51
      mmHg] and higher A(a)DO2 [149 +/- 48 versus 76 +/- 28 mmHg] values in overweight
      patients. During pneumoperitoneum, P(a)O2 transient increased above baseline
      values in overweight patients, whereas A(a)DO2 decreased. Hemodynamic parameters
      [HR, MAP, and CVP] did not differ significantly between groups. CONCLUSIONS:
      Arterial oxygenation and A(a)DO2 are significantly impaired in overweight
      patients under general anesthesia in Trendelenburg posture. In overweight
      patients pneumoperitoneum transient reduced the impairment of arterial
      oxygenation and lead to a decrease in A(a)DO2. Hemodynamic parameters were not
      affected by body weight.

PMID- 16568231
TI  - Which octogenarians do poorly after major open abdominal surgery in our Asian
      population?
AB  - BACKGROUND: As the elderly population grows and surgeons are faced with more
      octogenarians, there is a need to know how our Asian patients fair after major
      surgery. METHODS: A retrospective review of 125 octogenarians who underwent major
      abdominal surgery between January 1997 and September 2003 was performed.
      Preoperative condition was assessed using a weighted index of comorbidity used in
      Charlson Comorbidity Index and classification of patients according to the
      American Society of Anaesthesiologists (ASA). Outcome was measured as to whether
      complications developed, 30-day mortality and whether there was return to
      premorbid function. RESULTS: The patients had a mean age of 84.6 years (range: 80
      106). Nearly half (48.8%, n = 61) the cases were emergency cases. The median
      index of comorbidity was 3, and 29.6% of patients were classified either ASA III
      or IV. The operations were mostly stomach, small bowel or large bowel resection.
      Multivariate analysis revealed that emergency operations were associated with
      significantly increased odds of morbidity. The overall 30-day mortality was 5.6%,
      being only 4.7% for elective cases, despite high morbidity rates. ASA
      classification, comorbidity index >5, development of acute coronary syndrome and
      anastomotic leakage were found on multivariate analysis to significantly increase
      the odds of mortality. For elective cases, 82.8% of patients were able to return
      to their premorbid functional status. Development of complications and
      comorbidity index >5 were found to predict failure of its occurrence. Low serum
      albumin and haemoglobin and renal impairment were also predictors of adverse
      outcome. CONCLUSIONS: Efforts to improve outcome in geriatric surgery patients
      should emphasize a shift of attitude towards elective surgery rather than doing
      emergency operations when complications occur and also target the optimization of
      predictors of adverse outcome. Octogenarians should not be denied elective
      surgery.

PMID- 16568233
TI  - Oxidative DNA damage in cucumber cotyledons irradiated with ultraviolet light.
AB  - DNA was isolated from the cotyledons of cucumber seedlings irradiated with
      ultraviolet (UV)-C (254 nm) or UV-B+UV-A (280-360 nm; maximum energy at 312 nm)
      at various fluence rates and durations. Following enzymatic hydrolysis of DNA,
      the content of 8-hydroxy-2'-deoxyguanosine [(8-OHdG), 8-oxo-7,8-dihydro-2'
      deoxyguanosine], a well-established biomarker closely identified with
      carcinogenesis and aging in animal cells, was determined using a high-performance
      liquid chromatograph equipped with an electrochemical detector. The levels of 8
      OHdG increased with UV-C and UV-B irradiation in a fluence-dependent manner. This
      increase was also observed in etiolated cotyledons that had been excised from
      dark-grown cucumber seedlings and then cultured in vitro under UV light:
      monochromatic UV light at 270 nm or 290 nm increased the 8-OHdG level
      considerably, while UV at wavelengths above 310 nm had only small effects. In
      situ detection of H2O2 and quantification of H2O2 in plant extracts revealed that
      H2O2 accumulated in cotyledons irradiated with UV light. These results suggest
      that UV irradiation induces oxidative DNA damage in plant cells.

PMID- 16568235
TI  - Glycogen synthase kinase 3beta and Alzheimer's disease: pathophysiological and
      therapeutic significance.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder associated with
      cognitive and behavioral dysfunction and is the leading cause of dementia in the
      elderly. Several studies have implicated molecular and cellular signaling
      cascades involving the serine-threonine kinase, glycogen synthase kinase beta(GSK
      3beta) in the pathogenesis of AD. GSK-3beta may play an important role in the
      formation of neurofibrillary tangles and senile plaques, the two classical
      pathological hallmarks of AD. In this review, we discuss the interaction between
      GSK-3beta and several key molecules involved in AD, including the presenilins,
      amyloid precursor protein, tau, and beta-amyloid. We identify the signal
      transduction pathways involved in the pathogenesis of AD, including Wnt, Notch,
      and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.

PMID- 16568234
TI  - Amodal completion by baboons (Papio papio): contribution of background depth
      cues.
AB  - Four baboons (Papio papio) were tested in a computerized two-alternative forced
      choice task in which partially occluded graphic stimuli were shown either on
      linear perspective backgrounds depicting a corridor or on uniformly black
      backgrounds. The results indicated that baboons complete partly occluded stimuli
      and that amodal completion is facilitated by the display of pictorial background
      depth cues. Inter-individual differences emerged in the ability to extrapolate
      three-dimensional information from two-dimensional visual information.

PMID- 16568236
TI  - Regulation of mitochondrial oxidative phosphorylation by second messenger
      mediated signal transduction mechanisms.
AB  - The mitochondrial oxidative phosphorylation system is responsible for providing
      the bulk of cellular ATP molecules. There is a growing body of information
      regarding the regulation of this process by a number of second messenger-mediated
      signal transduction mechanisms, although direct studies aimed at elucidating this
      regulation are limited. The main second messengers affecting mitochondrial signal
      transduction are cAMP and calcium. Other second messengers include ceramide and
      reactive oxygen species as well as nitric oxide and reactive nitrogen species.
      This review focuses on available data on the regulation of the mitochondrial
      oxidative phosphorylation system by signal transduction mechanisms and is
      organised according to the second messengers involved, because of their pivotal
      role in mitochondrial function. Future perspectives for further investigations
      regarding these mechanisms in the regulation of the oxidative phosphorylation
      system are formulated.

PMID- 16568237
TI  - The vertebrate connexin family.
AB  - Connexins are chordate-specific transmembrane proteins that can form gap
      junctional channels between adjacent cells. With the progress in vertebrate
      genome sequencing, it is now possible to reconstruct the main lines in the
      evolution of the connexin family from fishes to mammals. Four connexin groups are
      only found in fishes. Otherwise, the differences between fishes and mammals can
      be explained by two gene losses (Cx39.9 and Cx43.4) after the divergence of the
      Reptilia, and three gene duplications (the generation of Cx26 and 30 from a
      preCx26/30 sequence, Cx30.3 and 31.1 from a preCx30.3/ 31.1 sequence, and Cx31.3
      from an uncertain origin). Orthologs of most connexins can be found throughout
      the vertebrates from fishes to mammals. As judged from the recently defined
      connexins in tunicates, the original connexin might be related to the ortholog
      groups of Cx36, 39.2, 43.4, 45 or 47.

PMID- 16568238
TI  - Hairpin RNA: a secondary structure of primary importance.
AB  - An RNA hairpin is an essential secondary structure of RNA. It can guide RNA
      folding, determine interactions in a ribozyme, protect messenger RNA (mRNA) from
      degradation, serve as a recognition motif for RNA binding proteins or act as a
      substrate for enzymatic reactions. In this review, we have focused on cis-acting
      RNA hairpins in metazoa, which regulate histone gene expression, mRNA
      localization and translation. We also review evolution, mechanism of action and
      experimental use of trans-acting microRNAs, which are coded by short RNA
      hairpins. Finally, we discuss the existence and effects of long RNA hairpin in
      animals. We show that several proteins previously recognized to play a role in a
      specific RNA stem-loop function in cis were also linked to RNA silencing pathways
      where a different type of hairpin acts in trans. Such overlaps indicate that the
      relationship between certain mechanisms that recognize different types of RNA
      hairpins is closer than previously thought.

PMID- 16568239
TI  - Recombinant G protein-coupled receptors from expression to renaturation: a
      challenge towards structure.
AB  - G protein-coupled receptors (GPCRS) represent a class of integral membrane
      proteins involved in many biological processes and pathologies. Fifty percent of
      all modern drugs and almost 25% of the top 200 bestselling drugs are estimated to
      target GPCRs. Despite these crucial biological implications, very little is
      known, at atomic resolution, about the detailed molecular mechanisms by which
      these membrane proteins are able to recognize their extra-cellular stimuli and
      transmit the associated messages. Obviously, our understanding of GPCR
      functioning would be greatly facilitated by the availability of high-resolution
      three-dimensional (3D) structural data. However, expression, solubilization and
      purification of these membrane proteins are not easy to achieve, and at present,
      only one 3D structure has been determined, that of bovine rhodopsin. This review
      presents and compares the different successful strategies which have been applied
      to solubilize and purify recombinant GPCRs in the perspective of structural
      biology experiments.

PMID- 16568240
TI  - Caveolin-1 interacts with the chaperone complex TCP-1 and modulates its protein
      folding activity.
AB  - We report that caveolin-1, one of the major structural protein of caveolae,
      interacts with TCP-1, a hetero-oligomeric chaperone complex present in all
      eukaryotic cells that contributes mainly to the folding of actin and tubulin. The
      caveolin-TCP-1 interaction entails the first 32 amino acids of the N-terminal
      segment of caveolin. Our data show that caveolin-1 expression is needed for the
      induction of TCP-1 actin folding function in response to insulin stimulation.
      Caveolin-1 phosphorylation at tyrosine residue 14 induces the dissociation of
      caveolin-1 from TCP-1 and activates actin folding. We show that the mechanism by
      which caveolin-1 modulates TCP-1 activity is indirect and involves the
      cytoskeleton linker filamin. Filamin is known to bind caveolin-1 and to function
      as a negative regulator of insulin-mediated signaling. Our data support the
      notion that the caveolin-filamin interaction contributes to restore insulin
      mediated phosphorylation of caveolin, thus allowing the release of active TCP-1.

PMID- 16568241
TI  - The clinical potential of sphingolipid-based therapeutics.
AB  - The era of sphingolipid-based therapeutics is upon us. A large body of work has
      been accumulating that demonstrates the distinct biological roles of
      sphingolipids in maintaining a homeostatic environment and in responding to
      environmental stimuli to regulate cellular processes. It is thus necessary to
      further investigate alterations in sphingolipid-metabolism in pathological
      conditions and, in turn, try to exploit altered sphingolipid-metabolizing enzymes
      and their metabolites as therapeutic targets. This review will examine how
      advances in the fields of drug delivery, drug discovery, synthetic chemistry,
      enzyme replacement therapy, immunobiology, infectious disease and nanotechnology
      have delivered the potential and promise of utilizing and/or targeting
      sphingolipid metabolites as therapies for diverse diseases.

PMID- 16568242
TI  - Insights into the genetic basis of congenital heart disease.
AB  - Cardiovascular malformations are the most common type of birth defect and result
      in significant mortality worldwide. The etiology for the majority of these
      anomalies remains unknown. Advances in the characterization of the molecular
      pathways critical for normal cardiac development have led to the identification
      of numerous genes necessary for this complex morphogenetic process. This work has
      aided the discovery of an increasing number of single genes being implicated as
      the cause of human cardiovascular malformations. This review summarizes normal
      cardiac development and outlines the recent discoveries of the genetic causes of
      congenital heart disease.

PMID- 16568244
TI  - The neurotrophic receptor TrkB: a drug target in anti-cancer therapy?
AB  - Increasing evidence implies altered signaling through the neurotrophic receptor
      tyrosine kinase TrkB in promoting tumor formation and metastasis. TrkB, sometimes
      in conjunction with its primary ligand BDNF, is often overexpressed in a variety
      of human cancers, ranging from neuroblastomas to pancreatic ductal
      adenocarcinomas, in which it may allow tumor expansion and contribute to
      resistance to anti-tumor agents. In vitro, TrkB acts as a potent suppressor of
      anoikis (detachment-induced apoptosis), which is associated with the acquisition
      of an aggressive tumorigenic and metastatic phenotype in vivo. In view of its
      predicted contribution to tumorigenicity and metastasis in humans, TrkB
      corresponds to a potential drug target, and preclinical models have already been
      established. The encouraging results of pharmacological Trk inhibitors in tumor
      xenograft models suggest that TrkB inhibition may represent a promising novel
      anti-tumor therapeutic strategy. This hypothesis is currently being evaluated in
      clinical trials. Here, we will discuss the latest developments on TrkB in these
      contexts as well as highlight some critical questions that remain to be addressed
      for evaluating TrkB as a therapeutic target in cancer.

PMID- 16568243
TI  - Magnetic resonance and the human brain: anatomy, function and metabolism.
AB  - The introduction and development, over the last three decades, of magnetic
      resonance (MR) imaging and MR spectroscopy technology for in vivo studies of the
      human brain represents a truly remarkable achievement, with enormous scientific
      and clinical ramifications. These effectively non-invasive techniques allow for
      studies of the anatomy, the function and the metabolism of the living human
      brain. They have allowed for new understandings of how the healthy brain works
      and have provided insights into the mechanisms underlying multiple disease
      processes which affect the brain. Different MR techniques have been developed for
      studying anatomy, function and metabolism. The primary focus of this review is to
      describe these different methodologies and to briefly review how they are being
      employed to more fully appreciate the intricacies associated with the organ,
      which most distinctly differentiates the human species from the other animal
      forms on earth.

PMID- 16568245
TI  - Stem cells and their niche: a matter of fate.
AB  - Embryonic stem cells provide an in vitro model for developmental biologists to
      study cell fate decisions during ontogenesis, while somatic stem cells allow
      physiologists to understand tissue homeostasis in the adult. The behavior of stem
      cells is dependent on an intimate relationship with a supportive niche. This
      brief review highlights some of the most important recent trends in stem cell
      biology, focusing in particular on the supportive microenvironments for both
      embryonic and adult stem cells. Known intrinsic and extrinsic molecular players
      from the best-characterized stem cell types are summarized, illuminating a number
      of shared environmental cues among tissues originating from all three embryonic
      germ layers.

PMID- 16568246
TI  - Beta-adrenergic receptors and nitric oxide generation in the cardiovascular
      system.
AB  - Nitric oxide plays a crucial role in cardiovascular homeostasis, with important
      vasodilatory, anti-thrombotic and anti-atherogenic properties. Beta-adrenergic
      receptors (betaARs), present on a wide variety of cardiovascular cells, including
      vascular endothelial cells, platelets, cardiac myocytes and leukocytes, have long
      been established as key players in maintaining cardiovascular homeostatic
      control. During the last few years a wealth of evidence has emerged which
      directly links stimulation of these cardiovascular betaARs to nitric oxide (NO)
      generation, suggesting a new and important mechanism of adrenergic control of
      cardiovascular function. This review explores the cardiovascular cell systems in
      which this coupling of betaARs and NO occurs, the intracellular signalling and
      regulatory mechanisms involved and the abnormalities in betaAR-NO oxide coupling
      found in cardiovascular disease states.

PMID- 16568247
TI  - Therapeutic strategies to ameliorate lysosomal storage disorders--a focus on
      Gaucher disease.
AB  - The lysosomal storage disorders encompass more than 40 distinct diseases, most of
      which are caused by the deficient activity of a lysosomal hydrolase leading to
      the progressive, intralysosomal accumulation of substrates such as sphingolipids,
      mucopolysaccharides, and oligosaccharides. Here, we primarily focus on Gaucher
      disease, one of the most prevalent lysosomal storage disorders, which is caused
      by an impaired activity of glucocerebrosidase, resulting in the accumulation of
      the glycosphingolipid glucosylceramide in the lysosomes. Enzyme replacement and
      substrate reduction therapies have proven effective for Gaucher disease cases
      without central nervous system involvement. We discuss the promise of chemical
      chaperone therapy to complement established therapeutic strategies for Gaucher
      disease. Chemical chaperones are small molecules that bind to the active site of
      glucocerebrosidase variants stabilizing their three-dimensional structure in the
      endoplasmic reticulum, likely preventing their endoplasmic reticulum-associated
      degradation and allowing their proper trafficking to the lysosome where they can
      degrade accumulated substrate to effectively ameliorate Gaucher disease.

PMID- 16568250
TI  - No loss of cardioprotection by postconditioning in connexin 43-deficient mice.
AB  - In situ hearts and isolated cardiomyocytes from heterozygous connexin 43
      deficient (Cx43+/-) mice cannot be protected by ischemic preconditioning or
      diazoxide. We have now addressed the role of connexin 43 in ischemic
      postconditioning (PC). Wild type (WT) and Cx43+/- mice were subjected to 30 min
      coronary occlusion and 120 min reperfusion, with and without a PC protocol of
      three cycles of 10 s coronary occlusion/10 s reperfusion. Infarct size (TTC
      staining) was reduced by PC from 54+/-5 to 37+/-3% of area at risk in WT.
      Likewise, infarct size was reduced by PC from 53+/-4 to 34+/-3% of area at risk
      in Cx43+/-. We conclude that connexin 43 is no prerequisite for PC's protection.
      To this end, the signal transduction of ischemic preconditioning and
      postconditioning differs.

PMID- 16568249
TI  - Self-reported psychopathology, adaptive functioning and sense of coherence, and
      psychiatric diagnosis among young men--a population-based study.
AB  - OBJECTIVE: To study the associations between psychiatric disorders and self
      perceived problems among adolescent boys. METHOD: The study population consisted
      of 2348 Finnish boys born during 1981 attending obligatory military call-up
      (79.7% of the original sample). At military call-up in 1999, the boys filled in
      the Young Adult Self-Report (YASR) and Orientation of Life Questionnaire (SOC
      13). Information about psychiatric disorders was obtained from the national
      military register during the years 1999-2004. RESULTS: Most of the
      psychopathology, adaptive functioning and SOC scales were associated with a
      variety of psychiatric disorders at follow-up. However, when the effects of
      scales were controlled in multivariate analysis, only YASR somatic problems and
      SOC-13 showed an independent association with a wide range of psychiatric
      disorders at follow-up. Poor SOC-13 predicted anxiety, depression, antisocial
      personality and substance use disorders. The YASR somatic problems scale
      predicted anxiety, depression, substance use, psychotic, and adjustment
      disorders. Self-reported delinquency and poor competence at school predicted
      substance use and antisocial personality disorders. CONCLUSIONS: Self-reports of
      poor sense of coherence and somatic complaints have a non-specific association
      with a wide range of psychiatric disorders. Clinical and theoretical implications
      of these findings are discussed.

PMID- 16568248
TI  - Lipid-lowering drugs.
AB  - Although a change in life-style is often the method of first choice for lipid
      lowering, lipid-lowering drugs, in general, help to control elevated levels of
      different forms of lipids in patients with hyperlipidemia. While one group of
      drugs, statins, lowers cholesterol, the other group, fibrates, is known to take
      care of fatty acids and triglycerides. In addition, other drugs, such as
      ezetimibe, colesevelam, torcetrapib, avasimibe, implitapide, and niacin are also
      being considered to manage hyperlipidemia. As lipids are very critical for
      cardiovascular diseases, these drugs reduce fatal and nonfatal cardiovascular
      abnormalities in the general population. However, a number of recent studies
      indicate that apart from their lipid-lowering activities, statins and fibrates
      exhibit multiple functions to modulate intracellular signaling pathways, inhibit
      inflammation, suppress the production of reactive oxygen species, and modulate T
      cell activity. Therefore, nowadays, these drugs are being considered as possible
      therapeutics for several forms of human disorders including cancer, autoimmunity,
      inflammation, and neurodegeneration. Here I discuss these applications in the
      light of newly discovered modes of action of these drugs.

PMID- 16568251
TI  - Remodeling of myocardial sleeve and gap junctions in canine superior vena cava
      after rapid pacing.
AB  - OBJECTIVE: We studied the response of the superior vena cava (SVC) myocardial
      sleeve to atrial fibrillation (AF). METHODS AND RESULTS: We examined adult male
      dogs without pacing (N=6) and after rapid atrial pacing (600 bpm) for 2 weeks
      (P2w; N=5) and 6-8 weeks (P6-8w; N=5). After pacing, the sleeve was increased in
      thickness (non-paced vs. either paced group, both P<0.05). This was associated
      with an increase in proliferative activity, which was higher in the P2w than the
      P6-8w animals (P<0.05). In addition, collagen content increased, and the
      component cardiomyocytes become more unevenly oriented and shorter and narrower
      in shape (non-paced vs. either paced group, both P<0.05). Pacing had different
      effects on connexin40 (Cx40) and Cx43 gap junctions. There was a 98% increase in
      Cx43 signal in P2w, and a 74% increase in P6-8w animals (non-paced vs. each paced
      group, both P<0.05). In contrast, Cx40 signal decreased 47% in P2w but increased
      44% in P6-8w animals (non-paced vs. each paced group, both P<0.05). CONCLUSIONS:
      Rapid atrial pacing results in a specific pattern of remodeling of the canine SVC
      sleeve, including changes in size and shape, spatial orientation, and gap
      junction expression profile of the component cardiomyocytes. These changes may co
      operatively affect the electrical properties and contribute to the formation and
      maintenance of the arrhythmogenic substrate of AF.

PMID- 16568253
TI  - Refining the application of direct embryogenesis in sugarcane: Effect of the
      developmental phase of leaf disc explants and the timing of DNA transfer on
      transformation efficiency.
AB  - A rapid in vitro protocol using direct somatic embryogenesis and microprojectile
      bombardment was investigated to establish the developmental phases most suitable
      for efficient sugarcane transformation. Immature leaf roll disc explants with and
      without pre-emergent inflorescence tissue were compared. It was shown that for
      effective transformation to occur, explants should be cultured for several days
      to allow initiation of embryo development prior to bombardment. Leaf roll discs
      with pre-emergent inflorescences showed a higher degree of embryogenic competence
      than non-flowering explants, and transformation efficiency was higher when
      explants containing floral initials were bombarded. Despite the occurrence of
      high numbers of phenotypically negative plants, combining the use of inflorescent
      leaf roll discs with direct embryogenic regeneration has the potential to improve
      the speed and efficiency of transgenesis in sugarcane.

PMID- 16568252
TI  - The regulation of Saccharomyces cerevisiae FLO gene expression and Ca2+ 
      dependent flocculation by Flo8p and Mss11p.
AB  - The ability of many microorganisms to modify adhesion-related properties of their
      cell surface is of importance for many processes, including substrate adhesion,
      cell-cell adhesion, invasive growth, pathogenic behaviour and biofilm formation.
      In the yeast Saccharomyces cerevisiae, a group of structurally related, cell-wall
      associated proteins encoded by the FLO gene family are directly responsible for
      many of the cellular adhesion phenotypes displayed by this organism. Previous
      research has suggested that the differential transcription of FLO genes
      determines specific adhesion phenotypes. However, the transcriptional regulation
      of most FLO genes remains poorly understood. Here we show that the
      transcriptional activator Mss11p, which has previously been shown to be involved
      in the regulation of starch degradation, the formation of pseudohyphae and
      haploid invasive growth, also acts as a strong inducer of flocculation. The data
      indicate that Mss11p induces flocculation together with Flo8p, and that FLO1 is
      the dominant target gene of the two factors in this process. The deletion of
      MSS11 leads to a non-flocculent phenotype, and specific domains of Mss11p that
      are critical for the induction of flocculation are identified. The data clearly
      show that several essential transcription factors are shared by at least two
      flocculation genes that control different adhesion phenotypes.

PMID- 16568255
TI  - [Bladder cancer--what's new].

PMID- 16568254
TI  - Identification of a potential structural marker for embryogenic competency in the
      Brassica napus spp. oleifera embryogenic tissue.
AB  - The Brassica napus secondary embryogenesis system requires no exogenous growth
      regulator to stimulate embryo development. It is stable embryogenically over a
      long period of culture and has a distinct pre-embryogenic stage. This system was
      used to investigate the morphological and cellular changes occurring in the
      embryogenic tissue compared to non-embryogenic tissue using various microscopy
      techniques. A unique ultrastructural feature designated the extracellular matrix
      (ECM) was observed on the surface of pre-embryogenic embryoids but not on the non
      embryogenic individuals. The ECM layer was found to be dominant in the pre
      embryogenic stage and reduced to fragments during embryo growth and development
      in mature embryogenic tissue. This is a novel aspect of the phenotype previously
      unreported in the Brassica system. This structure might be linked to acquisition
      of embryogenic competence.

PMID- 16568256
TI  - [Magnetic resonance imaging in orthopaedic medicine].
AB  - Magnetic resonance imaging (MRI) is an established diagnostic tool in
      orthopaedics. Superior soft tissue contrast, lack of ionised radiation and free
      slice orientation are the key points for optimal evaluation of joint structures,
      muscles and ligaments. Application of contrast agents improves the detection of
      inflammation and tumour tissue. However, measuring and interpretation of magnetic
      resonance imaging is a challenge both for orthopaedists and radiologists. Basic
      requirements for good diagnosis are clinical findings, plain radiographs and a
      clear indication. This report provides information about the method of magnetic
      resonance imaging, artefacts, indications, risks and drawbacks as well as
      limitations of this method that necessitate alternative imaging modalities.

PMID- 16568257
TI  - [Therapeutic splitting as standard treatment for cholelithiasis].
AB  - At the moment, therapeutic splitting is still regarded by the vast majority of
      surgeons as the gold standard for stones in the common bile duct. Endoscopic
      clearance of the duct certainly is much less invasive than open exploration.
      However, this does not apply when compared with laparoscopic stone removal. Both
      are equivalent in respect to stone clearance rates, but the laparoscopic
      techniques protect patients from the long-term sequelae of endoscopic
      papillotomy. This can be important particularly for younger patients.
      Laparoscopic bile duct exploration is cost-effective and safe. Special experience
      in laparoscopic surgical techniques, however, is mandatory. Thus, surgeons should
      intensify their training in laparoscopic bile duct exploration in order to
      increase the acceptance of these techniques.

PMID- 16568258
TI  - [Surgical therapy of hilar cholangiocarcinoma].
AB  - Surgical resection provides the only chance of cure for patients suffering from
      hilar cholangiocarcinoma. Due to the central anatomic localization within the
      liver hilum, established guidelines of oncologic surgery are difficult to apply.
      Resection of the hilar bifurcation alone or in combination with limited hepatic
      resection can be performed with low morbidity and low mortality but shows a high
      rate of local tumor recurrence. Usually, extended resection is required to
      achieve adequate safety margins. Right trisectionectomy complies best with the
      basic rules of oncologic surgery while allowing the maximum safety margin. The 5
      year survival rates reported after right trisectionectomy range between 20% and
      40% and reach 59% in selected patients. The increasing experience with living
      donor transplantation and recent advances in neoadjuvant tumor therapy may lead
      to renewed discussion of liver transplantation in hilar cholangiocarcinoma.

PMID- 16568260
TI  - Influence of the SLCO1B1*1b and *5 haplotypes on pravastatin's cholesterol
      lowering capabilities and basal sterol serum levels.
AB  - We previously showed that variant SLCO1B1 haplotype *1b (A388G) accelerates and
      that *5 (T521C) delays hepatocellular uptake of the HMG-CoA reductase inhibitor
      pravastatin [Mwinyi et al. (2004): Clin Pharmacol Ther 75:415-421]. In the
      present study we checked for differential effects of variant SLCO1B1 haplotypes
      on hepatocellular cholesterol synthesis. We analyzed the serum levels of
      cholesterol, lathosterol, and campesterol in healthy white males which had been
      grouped on the basis of their SLCO1B1 haplotype: *1a (n=10), *1b (n=10), and *5
      (n=8). The subjects received a single oral dose of 40 mg pravastatin. Cholesterol
      and lathosterol levels were lower in all subjects following pravastatin intake
      for up to 24. Median levels 6 h post-dosing of lathosterol decreased in each
      SLCO1B1 haplotype group in the rank order of *1b (-0.11 mg dl(-1); min-max: -0.20
      to -0.04; p=0.005) > *1a (-0.09 mg dl(-1); min-max: -0.22 to -0.05; p=0.005) > *5
      (-0.07 mg dl(-1); min-max: -0.17 to -0.05; p=0.012). Lathosterol median-change
      values were significantly greater in haplotype *1b than in haplotype *5
      individuals (p=0.041, non-adjusted), which was congruent with the extent of mean
      changes in lathosterol-to-cholesterol ratios, although the latter did not reach
      statistical significance. Post-treatment serum levels of campesterol were not
      affected by SLCO1B1 haplotype. Interestingly, sterol basal serum levels tended to
      be highest in *1b carriers, followed by those in *1a and *5 individuals, with
      significant differences in lathosterol concentrations between the *1b and *5
      (p=0.041, non-adjusted) haplotype group. Our findings suggest an association of
      SLCO1B1*1b and *5 haplotypes to pravastatin's inhibition of the hepatocellular
      HMG-CoA reductase. Furthermore, SLCO1B1 haplotypes seem to play a role in basal
      cholesterol homeostasis.

PMID- 16568259
TI  - Type 1 diabetes in Japan.
AB  - Type 1 diabetes is a multifactorial disease which results from a T-cell-mediated
      autoimmune destruction of the pancreatic beta cells in genetically predisposed
      individuals. The risk for individuals of developing type 1 diabetes varies
      remarkably according to country of residence and race. Japan has one of the
      lowest incidence rates of type 1 diabetes in the world, and recognises at least
      three subtypes of the condition: acute-onset ('classical'), slow-onset, and
      fulminant type 1 diabetes. The incidence rate of type 1 diabetes in children aged
      0-14 years in Japan increased over the period from 1973-1992, but remained
      constant over the last decade, averaging 2.37 cases per 100,000 persons per year;
      the incidence does not appear to have increased in older age groups. Although
      there are few reports regarding the incidence and prevalence of type 1 diabetes
      in adult-onset patients, it appears that the prevalence of type 1 diabetes in
      adults is more than twice that in childhood-onset patients and that two-thirds of
      them have a slow-onset form of type 1 diabetes. Differences and similarities in
      the association of MHC and non-MHC genes with type 1 diabetes are observed in
      Japan and in countries with Caucasoid populations. Highly susceptible class II
      HLA haplotypes identified in patients of Caucasoid origin are rarely seen in
      Japanese patients, whereas protective haplotypes are universal. Non-MHC genes
      associated with susceptibility to type 1 diabetes in both Japanese and Caucasoid
      patients include polymorphisms in the insulin gene, the cytotoxic T-lymphocyte
      antigen 4 (CTLA4) gene, the interleukin-18 (IL18) gene and the major
      histocompatibility complex class I chain-related gene A (MICA) gene. Fulminant
      type 1 diabetes is a unique subtype of type 1 diabetes that accounts for about
      20% of acute-onset type 1 diabetes, and is seen mainly in adults. The challenge
      for the future is to investigate the underlying pathogenesis of beta cell
      destruction, including the genetic or environmental factors that may modify the
      form of onset for each subtype of Japanese type 1 diabetes.

PMID- 16568261
TI  - Immunostimulation by induced expression of NKG2D and its MIC ligands in HTLV-1
      associated neurologic disease.
AB  - The NKG2D receptor costimulates effector/memory CD8 T cells and is normally
      absent on CD4 T cells but can be induced by T cell antigen receptor complex
      stimulation and interleukin-15 (IL-15). Among its ligands are the human major
      histocompatibility complex class I-related MICA and MICB, which have a restricted
      tissue distribution but are frequently associated with malignancies and some
      microbial infections. Moreover, aberrant expression of MIC may promote autoimmune
      disease progression. Human T cell lymphotropic virus type I (HTLV-1)-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory
      disease of the central nervous system that resembles multiple sclerosis. Disease
      progression involves production of IL-15 and its receptor through transactivation
      by the viral Tax regulator protein, an activated immune response state, and local
      cytokine production and T cell fratricide by Tax-specific cytotoxic T lymphocytes
      (CTL). This study shows that as with CD8 T cells, substantial proportions of
      HAM/TSP patient CD4 T cells are positive for NKG2D and that large numbers of T
      cells from both subsets express MIC, which can be transactivated by Tax
      independent of nuclear factor kappaB. Engagement of MIC by NKG2D promotes
      spontaneous HAM/TSP T cell proliferation and, apparently, CTL activities against
      HTLV-1-infected T cells. These results reveal a viral strategy that may exploit
      immune stimulatory mechanisms to negotiate a balance between promotion and
      limitation of infected host T cell expansions.

PMID- 16568262
TI  - Diversity and duplication of DQB and DRB-like genes of the MHC in baleen whales
      (suborder: Mysticeti).
AB  - The molecular diversity and phylogenetic relationships of two class II genes of
      the baleen whale major histocompatibility complex were investigated and compared
      to toothed whales and out-groups. Amplification of the DQB exon 2 provided
      sequences showing high within-species and between-species nucleotide diversity
      and uninterrupted reading frames consistent with functional class II loci found
      in related mammals (e.g., ruminants). Cloning of amplified products indicated
      gene duplication in the humpback whale and triplication in the southern right
      whale, with average nucleotide diversity of 5.9 and 6.3%, respectively, for
      alleles of each species. Significantly higher nonsynonymous divergence at sites
      coding for peptide binding (32% for humpback and 40% for southern right)
      suggested that these loci were subject to positive (overdominant) selection. A
      population survey of humpback whales detected 23 alleles, differing by up to 21%
      of their inferred amino acid sequences. Amplification of the DRB exon 2 resulted
      in two groups of sequences. One was most similar to the DRB3 of the cow and
      present in all whales screened to date, including toothed whales. The second was
      most similar to the DRB2 of the cow and was found only in the bowhead and right
      whales. Both loci showed low diversity among species and apparent loss of
      function or altered function including interruption of reading frames. Finally,
      comparison of inferred protein sequence of the DRB3-like locus suggested
      convergence with the DQB, perhaps resulting from intergenic conversion or
      recombination.

PMID- 16568264
TI  - Properties of the prototype 256-row (cone beam) CT scanner.
AB  - We evaluated Feldkamp artifacts, which are specific to cone-beam computed
      tomography (CT), in phantom and clinical studies using the 256-multidetector-row
      CT (256MDCT), and compared the reconstruction accuracy of axial and helical
      scans. Image noise, slice sensitivity profile (SSP) and artifacts with the
      256MDCT were evaluated using a phantom, and the results were compared to those of
      a 64MDCT. We also examined chest and abdomen scans produced with the 256MDCT in
      volunteers. For the axial scan, Feldkamp artifacts were visualized as high
      frequency streak-like artifacts that are oriented horizontally at the edge of the
      scan region in the phantom study. Similar results were obtained with the
      volunteers in soft-tissue regions near either bony structures or air pockets.
      Feldkamp artifacts with the 256MDCT can lead to misdiagnosis if not correctly
      identified and minimized via helical scanning. Image noise was less for axial
      than helical scans, while SSP was better with helical than axial scans. Feldkamp
      artifacts observed in the 256MDCT images, however, did not generally affect the
      interpretation of images. The 256MDCT promises more accurate diagnosis, and will
      provide volumetric cine images of wider cranio-caudal coverage, enabling new
      applications of CT.

PMID- 16568263
TI  - Isolation of major histocompatibility complex Class I genes from the tammar
      wallaby (Macropus eugenii).
AB  - The major histocompatibility complex (MHC) plays an essential role in the
      adaptive immune system of vertebrates through antigen recognition. Although MHC
      genes are found in all vertebrates, the MHC region is dynamic and has changed
      throughout vertebrate evolution, making it an important tool for comparative
      genomics. Marsupials occupy an important position in mammalian phylogeny, yet the
      MHC of few marsupials has been studied in detail. We report the isolation and
      analysis of expressed MHC Class I genes from the tammar wallaby, a model
      marsupial used extensively for the study of mammalian reproduction, genetics, and
      immunology. We determined that there are at least 11 Class I loci in the tammar
      genome and isolated six expressed Class I sequences from spleen and testes cDNA
      libraries, representing at least four loci. Two of the Class I sequences contain
      substitutions at sites known to be important for antigen binding, perhaps
      impacting their ability to bind peptides, or the types of peptide to which they
      bind. Phylogenetic analysis of tammar wallaby Class I sequences and other
      mammalian Class I sequences suggests that some tammar wallaby and red-necked
      wallaby loci evolved from common ancestral genes.

PMID- 16568266
TI  - Magic angle effect in MR imaging of ankle tendons: influence of foot positioning
      on prevalence and site in asymptomatic subjects and cadaveric tendons.
AB  - The influence of foot positioning on prevalence of the magic angle effect (MAE)
      in ankle tendons was investigated. In 30 asymptomatic volunteers and five
      cadaveric feet, MR imaging of the ankle was performed in the supine (neutral
      position of the foot) and prone (plantar-flexed foot) position. MAE was
      considered if increased T1-weighted signal at a certain site was seen in one
      position only. Histological correlation was obtained at 25 sites of the cadaveric
      posterior tibialis tendons (PTT). MAE occurred in 6/30 vs 1/30 (supine vs prone)
      anterior tibialis tendons (ATT), 30/30 vs 0/30 extensor hallucis longus and 27/30
      vs 0/30 extensor digitorum longus tendons, 29/30 vs 0/30 PTTs, 30/30 vs 0/30
      flexor digitorum and flexor hallucis longus tendons, 30/30 vs 1/30 peroneus
      brevis and 23/30 vs 1/30 peroneus longus tendons. At 12/25 cadaveric PTT sites
      where MAE was exclusively responsible for the increased signal, histology
      revealed normal tissue (11/12) or minimal degeneration (1/12). In conclusion, the
      supine body position with neutral position of the foot, a high prevalence (77
      100%) of MAE in ankle tendons except for the ATT (20%) is seen. MAE is almost
      absent in the prone body position with plantar flexion of the foot.

PMID- 16568265
TI  - Multidetector CT of the kidney.
AB  - The technological development of multidetector CT offers new possibilities for
      better imaging of organic structures that can be used in diagnosis of the kidney.
      The thinner slices allow a better spatial resolution, and slice fusion allows
      improved contrast resolution. The isotropic voxel has been realized in the latest
      64-channel scanners. The image quality of arbitrarily reconstructed planes has
      arrived at the image quality of the scan plane. Faster scanning allows studies in
      different contrast phases, which is helpful for better discrimination of benign
      or malignant lesions especially in the highly vascularized kidney. Different
      phases of contrast uptake can be differentiated (arterial, cortico-medullary,
      nephrographic, and excretory phase). Multidetector CT brings along the risk of
      increased dose due to thinner slice collimation and overranging phenomena.
      Indications for CT investigation of the kidney include urolithiasis, tumor
      diagnosis and staging, renal trauma, and vascular disease. Even in children,
      special indications for CT of the kidney remain in polytrauma and tumor staging.
      Multidetector CT of the kidney has become a very valuable tool in urology, but a
      careful protocol strategy is mandatory.

PMID- 16568267
TI  - Dose reduction in multidetector CT of the urinary tract. Studies in a phantom
      model.
AB  - A novel ureter phantom was developed for investigations of image quality and dose
      in CT urography. The ureter phantom consisted of a water box (14 cm x 32 cm x 42
      cm) with five parallel plastic tubes (diameter 2.7 mm) filled with different
      concentrations of contrast media (1.88-30 mg iodine/ml). CT density of the tubes
      and noise of the surrounding water were determined using two multidetector
      scanners (Philips MX8000 with four rows, Siemens Sensation 16 with 16 rows) with
      varying tube current-time product (15-100 mAs per slice), voltage (90 kV, 100 kV,
      120 kV), pitch (0.875-1.75), and slice thickness (1 mm, 2 mm, 3.2 mm). Contrast
      to-noise ratio as a parameter of image quality was correlated with dose (CTDI)
      and was compared with image evaluation by two radiologists. The CT densities of
      different concentrations of contrast media and contrast-to-noise ratio were
      significantly higher when low voltages (90 kV versus 120 kV, 100 kV versus 120
      kV) were applied. Smaller slice thickness (1 mm versus 2 mm) did not change CT
      density but decreased contrast-to-noise ratio due to increased noise. Contrast
      phantom studies showed favourable effects of low tube voltage on image quality in
      the low dose range. This may facilitate substantial dose reduction in CT
      urography.

PMID- 16568268
TI  - Visual targeting of components of floral colour patterns in flower-naive
      bumblebees (Bombus terrestris; Apidae).
AB  - Floral colour patterns are contrasting colour patches on flowers, a part of the
      signalling apparatus that was considered to display shape and colour signals used
      by flower-visitors to detect flowers and locate the site of floral reward. Here,
      we show that flower-naive bumblebees (Bombus terrestris) spontaneously direct
      their approach towards the outside margin of artificial flowers, which provides
      contrast between these dummy flowers and the background. If no floral guides are
      present, the bumblebees continue to approach the margin and finally touch the
      marginal area of the dummy flower with the tips of their antennae. Whilst
      approaching dummy flowers that also have a central floral guide, the bumblebees
      change their direction of flight: Initially, they approach the margin, later they
      switch to approaching the colour guide, and finally they precisely touch the
      floral guide with their antennae. Variation of the shape of equally sized dummy
      flowers did not alter the bumblebees' preferential orientation towards the guide.
      Using reciprocal combinations of guide colour and surrounding colour, we showed
      that the approach from a distance towards the corolla and the antennal contact
      with the guide are elicited by the same colour parameter: spectral purity. As a
      consequence, the dummy flowers eliciting the greatest frequency of antennal
      reactions at the guide are those that combine a floral guide of high spectral
      purity with a corolla of less spectral purity. Our results support the hypothesis
      that floral guides direct bumblebees' approaches to the site of first contact
      with the flower, which is achieved by the tips of the antennae.

PMID- 16568269
TI  - Initial guesses generation for Fluorescence Intensity Distribution Analysis.
AB  - The growing number of applications of Fluorescence Intensity Distribution
      Analysis (FIDA) demands for new approaches in data processing, aiming at
      increased speed and robustness. Iterative algorithms of parameter estimation,
      although proven to be universal and accurate, require some initial guesses (IG)
      of the unknown parameters. An essential component of any data processing
      technology, IG become especially important in case of FIDA, since even with
      apparently reasonable, and physically admissible but randomly chosen IG, the
      iterative procedure may converge to situations where the FIDA model cannot be
      evaluated correctly. In the present work we introduce an approach for IG
      generation in FIDA experiments based on the method of moments. IG are generated
      for the sample parameters: brightness, concentration, and for the parameters
      related to experimental set-up: background, observation volume profile. A number
      of analytical simplifications were introduced in order to increase the accuracy
      and robustness of the numerical algorithms. The performance of the developed
      method has been tested on number of simulations and experimental data. Iterative
      fitting with generated IG proved to be more robust and at least five times faster
      than with an arbitrarily chosen IG. Applicability of the proposed method for
      quick estimation of brightness and concentrations is discussed.

PMID- 16568270
TI  - Detecting fluorescent protein expression and co-localisation on single secretory
      vesicles with linear spectral unmixing.
AB  - Many questions in cell biology and biophysics involve the quantitation of co
      localisation and the interaction of proteins tagged with different fluorophores.
      However, the incomplete separation of the different colour channels due to the
      presence of autofluorescence, along with cross-excitation and emission "bleed
      through" of one colour channel into the other, all combine to render the
      interpretation of multi-band images ambiguous. Here we introduce a new live-cell
      epifluorescence spectral imaging and linear unmixing technique for classifying
      resolution-limited point objects containing multiple fluorophores. We demonstrate
      the performance of our technique by detecting, at the single-vesicle level, the
      co-expression of the vesicle-associated membrane protein, VAMP-2 (also called
      synaptobrevin-2), linked to either enhanced green fluorescent protein (EGFP) or
      citrine [a less pH-sensitive variant of enhanced yellow fluorescent protein
      (EYFP)], in mouse cortical astrocytes. In contrast, the co-expression of VAMP-2
      citrine and the lysosomal transporter sialine fused to EGFP resulted in little
      overlap. Spectral imaging and linear unmixing permit us to fingerprint the
      expression of spectrally overlapping fluorescent proteins on single secretory
      organelles in the presence of a spectrally broad autofluorescence. Our technique
      provides a robust alternative to error-prone dual- or triple colour co
      localisation studies.

PMID- 16568271
TI  - Culture conditions improving the production of jadomycin B.
AB  - The jadomycins are a unique family of benzoxazolophenanthridine antibiotics
      produced by Streptomyces venezuelae ISP5230 following heat or ethanol shock or
      phage infection. We have modified the culture conditions by altering the carbon
      source, buffer, inoculum size, and timing of ethanol shock, thereby reducing
      growing times and improving jadomycin B production. Our optimized conditions use
      glucose as the carbon source, MOPS as buffer, low concentrations of phosphate, a
      defined inoculum concentration and an immediate ethanol shock to induce jadomycin
      B production; results that contrast previous studies. The altered media will
      facilitate the isolation of related jadomycin B congeners.

PMID- 16568272
TI  - A weighted measure for the similarity analysis of DNA sequences.
AB  - Here we propose a weighted measure for the similarity analysis of DNA sequences.
      It is based on LZ complexity and (0,1) characteristic sequences of DNA sequences.
      This weighted measure enables biologists to extract similarity information from
      biological sequences according to their requirements. For example, by this
      weighted measure, one can obtain either the full similarity information or a
      similarity analysis from a given biological aspect. Moreover, the length of DNA
      sequence is not problematic. The application of the weighted measure to the
      similarity analysis of beta-globin genes from nine species shows its flexibility.

PMID- 16568273
TI  - Pathophysiological mechanism and immediate treatment of retrograde cerebral
      venous air embolism.

PMID- 16568275
TI  - Early post-traumatic heterotopic mesenteric ossification: report of a case.

PMID- 16568274
TI  - Avian influenza (H5N1): implications for intensive care.
AB  - BACKGROUND: As influenza A/H5N1 spreads around the globe the risk of an epidemic
      increases. DISCUSSION: Review of the cases of influenza A/H5N1 reported to date
      demonstrates that it causes a severe illness, with a high proportion of patients
      (63%) requiring advanced organ support. Of these approx. 68% develop multiorgan
      failure, at least 54% develop acute respiratory distress syndrome, and 90% die.
      Disease progression is rapid, with a median time from presentation to hospital to
      requirement for advanced organ support of only 2 days. CONCLUSION: The infectious
      nature, severity and clinical manifestations of the disease and its potential for
      pandemic spread have considerable implications for intensive care in terms of
      infection control, patient management, staff morale and intensive care expansion.

PMID- 16568277
TI  - Detecting emergent effects of multiple predator species.
AB  - When foraging together, multiple predator species that share a single prey often
      cause prey mortality that cannot be predicted based on knowledge of predation by
      each species separately. Modeling and managing the effects of multiple predator
      species depend on accurately assessing these combined effects. Two methods are
      currently used to experimentally examine combined predation by multiple predator
      species: the additive and substitutive experimental designs. I simultaneously
      employed both experimental designs to examine predation by two crab species on
      shared mussel prey. I show that the two methods yield results that disagree both
      quantitatively and qualitatively, leading to very different conclusions about the
      way that predator species combine to affect prey mortality. This discrepancy
      occurred because the two methods examine complimentary, but not interchangeable
      questions. I advocate using an experimental design that incorporates both
      additive and substitutive designs to achieve a more complete understanding of the
      combined effects of multiple predator species.

PMID- 16568276
TI  - Limited spread of innovation in a wild parrot, the kea (Nestor notabilis).
AB  - In the local population of kea in Mount Cook Village, New Zealand, some keas open
      the lids of rubbish bins with their bill to obtain food scraps within. We
      investigated the extent to which this innovation has spread in the local
      population, and what factors limit the acquisition of bin opening. Only five
      males of 36 individually recognised birds were observed to have performed
      successful bin opening. With one exception there were always other keas present,
      watching successful bin opening. Seventeen additional individuals were seen to
      have benefitted from lid opening. Their foraging success was less than that of
      the bin openers. Social status of bin openers did not differ from scrounging
      males. Among the individuals that were regularly seen at the site of the bins but
      were not successful in bin opening, social status and the ratio of feeding
      directly from open bins correlated with the amount of opening attempts. We
      conclude that scrounging facilitated certain behavioural aspects of bin opening
      rather than inhibiting them. The fact that only 9% of opening attempts were
      successful, and the long period of time required to increase efficiency in lid
      opening shows that mainly individual experience, and to a lesser extent insight
      and social learning, play key roles in acquisition of the opening technique. The
      results indicate that the spread of innovative solutions of challenging
      mechanical problems in animals may be restricted to only a few individuals.

PMID- 16568278
TI  - The mixotroph Ochromonas tuberculata may invade and suppress specialist phago-
      and phototroph plankton communities depending on nutrient conditions.
AB  - Mixotrophic organisms combine light, mineral nutrients, and prey as supplementary
      resources. Based on theoretical assumptions and field observations, we tested
      experimentally the hypothesis that mixotrophs may invade established plankton
      communities depending on the trophic status of the system, and investigated
      possible effects on food web structure, species diversity, and nutrient dynamics.
      To test our hypothesis, we inoculated the mixotrophic nanoflagellate Ochromonas
      tuberculata into established planktonic food webs, consisting of specialist
      phototrophs, specialist phagotrophs, and bacteria at different supplies of
      soluble inorganic nutrients and dissolved organic carbon. Oligotrophic systems
      facilitated the invasion of O. tuberculata in two different ways. First, the
      combination of photosynthesis and phagotrophy gave mixotrophs a competitive
      advantage over specialist phototrophs and specialist phagotrophs. Second, low
      nutrient supplies supported the growth of small plankton organisms that fell into
      the food size spectrum of mixotrophs. Conversely, high nutrient supplies
      prevented O. tuberculata from successfully invading the food webs. Two important
      conclusions were derived from our experiments. First, in contrast to a paradigm
      of ecology, specialization may not necessarily be the most successful strategy
      for survival under stable conditions. Indeed, the use of several resources with
      lower efficiency can be an equally, or even more, successful strategy in nature.
      Second, when limiting nutrients promote the growth of bacterio- and
      picophytoplankton, invading mixotrophs may have a habitat-ameliorating effect for
      higher trophic levels, gauged in terms of food quantity and quality. Using given
      resources more efficiently, O. tuberculata generated higher biomasses and
      expressed an increased nutritional value for potential planktivores, due to
      decreased cellular carbon to phosphorus (C:P) ratios compared to specialized
      plankton taxa. Our findings may help to explain why energy transfer efficiency
      between phytoplankton and higher trophic levels is generally higher in
      oligotrophic systems than in nutrient rich environments.

PMID- 16568279
TI  - Competition for pulsed resources: an experimental study of establishment and
      coexistence for an arid-land grass.
AB  - In arid environments, episodically-pulsed resources are important components of
      annual water and nutrient supply for plants. This study set out to test whether
      seedlings have an increased capacity for using pulsed resources, which might then
      improve establishment when in competition with older individuals. A second aim
      was to determine whether there is a trade-off in competitive strategies when
      resources are supplied continuously at low concentrations, or as pulses with
      pronounced inter-pulse periods. A glasshouse experiment used a target-neighbour
      design of size-asymmetric competition, with juveniles of Panicum antidotale (blue
      panicgrass) introduced into contrasting densities of adult plants. Stable
      isotopes of nitrogen were used for measuring plant resource uptake from pulses,
      and tolerance to inter-pulse conditions was assessed as the mean residence time
      (MRT) of nitrogen. A higher root/shoot ratio and finer root system enhanced the
      capacity of juveniles to use resources when pulsed, rather than when continuously
      supplied. Higher resource uptake during pulses improved the establishment of
      juvenile Panicum in mixed cultures with older individuals. However, a trade-off
      was observed in plant strategies, with juveniles showing a lower MRT for
      nitrogen, which suggested reduced tolerance to resource deficit during inter
      pulse periods. Under field conditions, higher utilization of pulsed resources
      would lead to the improved seedling establishment of Panicum adjacent to "nurse"
      plants, whereas mature plants with well-developed roots, exploiting a greater
      soil volume, maintain more constant resource uptake and retention during inter
      pulse periods.

PMID- 16568280
TI  - Sixteen-slice CT with volumetric analysis of foot fractures.
AB  - Computed tomography (CT) imaging of the foot demands excellent resolution for the
      delineation of complex fractures and joint alignment after trauma. The quality of
      current multislice volumetric acquisition results in exceptional multiplanar and
      3-D reconstructions, precluding the requirement for an additional acquisition in
      a second plane. This pictoral essay depicts fractures of various bones of the
      foot, with reference to recent investigative studies demonstrating the value of
      CT in the evaluation of foot fractures.

PMID- 16568281
TI  - Clinical quiz. Gallstone ileus with cholecystocolonic fistula.

PMID- 16568283
TI  - Effects of delay to reinforcement on the choice between cocaine and food in
      rhesus monkeys.
AB  - RATIONALE: Although a delay between behavior and reinforcer has been shown to
      weaken behavior, little is known about the effects of delay on drug choice.
      OBJECTIVES: The present study examined effects of delay between lever press and
      reinforcer presentation on the choice between a drug and non-drug reinforcer and
      between different drug doses. MATERIALS AND METHODS: Monkeys (n=4) were allowed
      to choose 32 times/day between cocaine and four food pellets. The delay between
      lever press and a preferred dose of cocaine (0.05 mg/kg/injection) was increased
      systematically from 0 to 240 s, while the delay to food remained at 0 s. A second
      group of monkeys (n=4) was allowed to choose between 0.05 mg/kg/injection and a
      lower dose of cocaine (0.025 mg/kg/injection). Next, a delay that resulted in
      less than 20% choice of 0.05 mg/kg/injection cocaine was selected and delay to
      the alternative was varied. RESULTS: Results were similar across groups. The
      choice of 0.05 mg/kg/injection approximated 100% at 0 delay and decreased to near
      0 as delay increased. As the delay to alternative was subsequently increased from
      0 to 240 s, choice of 0.05 mg/kg/injection increased, though full cocaine choice
      was not generally restored. The delay estimated to maintain 50% choice
      (indifference point) was lower for the cocaine-food choice (mean=64 s) than for
      the cocaine-cocaine choice (mean=207 s). CONCLUSIONS: This experiment
      demonstrates that the choice between cocaine and a non-drug or drug alternative
      can be modified by increasing the interval between behavior and drug injection.
      Overall, the results are consistent with a temporal discounting model of drug
      choice.

PMID- 16568284
TI  - GluDy allele variations in Aegilops tauschii and Triticum aestivum: implications
      for the origins of hexaploid wheats.
AB  - To investigate the evolution and geographical origins of hexaploid wheat, we
      examined a 284 bp sequence from the promoter region of the GluDy locus, coding
      for the y subunit of high-molecular-weight glutenin. Fourteen different alleles
      were found in 100 accessions of Aegilops tauschii and 169 of Triticum aestivum.
      Two alleles were present in both species; the other 7 alleles from Ae. tauschii
      and 5 from T. aestivum were unique to their respective species. The two shared
      alleles differed at only one nucleotide position within the region sequenced, but
      their apparent association with the common haplotypes GluD1a and GluD1d, which
      have substantial differences within their GluDy coding regions, makes it unlikely
      that the alleles evolved independently in Ae. tauschii and T. aestivum. The
      results therefore support previous studies which suggest that there were at least
      two Ae. tauschii sources that contributed germplasm to the D genome of T.
      aestivum. The number of alleles present in T. aestivum, and the nucleotide
      diversity of these alleles, indicates that this region of the D genome has
      undergone relatively rapid change since polyploidisation. Ae. tauschii from Syria
      and Turkey had relatively high nucleotide diversity and possessed all the major
      GluDy alleles, indicating that these populations are probably ancient and not the
      result of adventive spread. The presence in the Turkish population of both of the
      shared alleles suggests that hexaploid wheat is likely to have originated in
      southeast Turkey or northern Syria, within the Fertile Crescent and near to the
      farming villages at which archaeological remains of hexaploid wheats are first
      found. A second, more recent, hexaploidisation probably occurred in Iran.

PMID- 16568282
TI  - Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the
      bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes.
AB  - RATIONALE: Corticotropin-releasing factor (CRF) produces anxiety-like and
      aversive effects when infused directly into the various regions of the brain,
      including the bed nucleus of the stria terminalis (BNST). However, the CRF
      receptor subtypes within the BNST mediating these phenomena have not been
      established. OBJECTIVES: We used selective CRF receptor antagonists to determine
      the receptor subtypes involved in the anxiogenic-like and aversive effects CRF in
      the BNST. MATERIALS AND METHODS: Male Long-Evans rats were bilaterally infused
      with CRF (0.2 or 1.0 nmol) either alone or in combination with the CRF1 receptor
      antagonist CP154,526 or the CRF2 receptor antagonist anti-sauvagine 30 (AS30)
      before behavioral testing in the elevated plus maze or place conditioning
      paradigms. RESULTS: Intra-BNST administration of CRF produced a dose-dependent
      reduction in open arm entries and open arm time in the elevated plus maze,
      indicating an anxiogenic-like effect. These effects were inhibited by co-infusion
      of CP154,526 but not of AS30, indicating that the anxiogenic-like effects of CRF
      in the BNST are mediated by CRF1 receptors. Place conditioning with intra-BNST
      administration of CRF produced a dose-dependent aversion to the CRF-paired
      environment that was prevented by co-infusion of either CP154,526 or AS30,
      indicating that both CRF receptor subtypes mediate the aversive effects of this
      peptide. Intra-BNST infusions of the CRF receptor antagonists alone produced no
      effects in either behavioral paradigm. CONCLUSIONS: CRF1 receptors in the BNST
      mediate the anxiogenic-like effects of CRF in this region, whereas both CRF1 and
      CRF2 receptor subtypes mediate the conditioned aversive effects of this peptide
      within the BNST.

PMID- 16568285
TI  - Differential gene expression in Phaseolus vulgaris I locus NILs challenged with
      Bean common mosaic virus.
AB  - The Phaseolus vulgaris I locus-Bean common mosaic virus (BCMV; Potyviridae)
      pathosystem is of critical importance to bean geneticists, breeders and
      pathologists because of the worldwide distribution of both the virus and
      germplasm containing this resistance gene. In order to learn more about the
      molecular responses characteristic of this resistance gene, a cDNA-AFLP screen
      was conducted on homozygous NILs of P. vulgaris variety 'Black Turtle Soup' (BT),
      containing either the I locus allele for resistance (BT(II)) or susceptibility
      (BT(ii)) to BCMV. Eight conditions were compared in a factorial analysis: BT(II)
      versus BT(ii); mock inoculated versus BCMV inoculated; 26 versus 34 degrees C.
      Transcripts induced in response to viral infection and that were further
      responsive to temperature, genotype or both were isolated and cloned. Sequence
      analysis of the resultant clones revealed several classes of putative genes,
      including transcription-related and signal transduction-related genes. Review of
      disease resistance literature suggests further avenues of research involving the
      candidates isolated in this screen.

PMID- 16568286
TI  - Topographical distribution of typical unifocal congenital hypertrophy of retinal
      pigment epithelium.
AB  - PURPOSE: To describe the topographical distribution of typical congenital
      hypertrophy of retinal pigment epithelium (CHRPE) lesions in the ocular fundi.
      METHODS: Retrospective review of the clinical records of 52 patients with typical
      unifocal CHRPE. RESULTS: The 52 CHRPE lesions ranged from 2.5 mm to 11.5 mm in
      maximal basal diameter (mean=6.6 mm, SD=2.6 mm). The central point of the lesion
      was in the peripheral fundus in 44 eyes and in the intermediate fundus in eight
      eyes. The footprint of the lesion involved the peripheral fundus only in 25 eyes,
      both the intermediate and peripheral fundus in 22 eyes, and the intermediate
      fundus only in five eyes. The central point of the lesion was located in the
      temporal quadrant in 24 eyes, the inferior quadrant in 12 eyes, the nasal
      quadrant in nine eyes, and the superior quadrant in seven eyes. No lesion in this
      series involved the posterior fundus. CONCLUSIONS: The most common fundus
      location for typical unifocal CHRPE in this series was the peripheral fundus
      temporally. Although posterior fundus location of CHRPE has been reported
      occasionally, our study suggests that such a location is very uncommon.

PMID- 16568287
TI  - Development of visual pursuit in the first 6 years of life.
AB  - BACKGROUND: There are few previous investigations on the development of smooth
      visual pursuit in children. The aim of this study was to determine normative
      values for the development of horizontal and vertical smooth pursuit in a large
      number of normal children. METHODS: Eye movements of 358 healthy children aged 6
      weeks through 6 years were recorded using infrared photo-oculography. Visual
      pursuit was elicited with colored squares of 1.2 degrees of visual angle. The
      stimulus moved horizontally or vertically with constant velocities of 7.5, 15, or
      30 degrees/s. RESULTS: Attention time increased with increasing age from 0.54 to
      0.77 (P<0.01) and decreased with increasing stimulus velocities (P<0.01). The
      ratio of time of smooth pursuit to time of smooth pursuit plus saccades increased
      with increasing age from 0.63 to 0.78 (P<0.01) and decreased with increasing
      stimulus velocities (P<0.01). For stimulus velocities of 7.5 degrees/s, no
      significant difference was found between horizontal and vertical gain values. For
      stimulus velocities of 15 degrees/s and 30 degrees/s, gains for horizontal
      movements were larger that for vertical (P<0.05). Increasing stimulus speeds were
      associated with decreasing gains (P<0.05). CONCLUSIONS: This study provides the
      following normative values for photo-oculography in healthy children aged 6 weeks
      through 6 years of age: attention time, smooth pursuit time, and gain for three
      stimulus velocities presented horizontally and vertically. This normative
      database should help to diagnose pathologic ophthalmological or neuropediatric
      conditions, to perform screening interventions, and to initiate therapies.

PMID- 16568290
TI  - The distal tibiofibular syndesmosis during passive foot flexion. RSA-based study
      on intact, ligament injured and screw fixed cadaver specimens.
AB  - INTRODUCTION: The aim of the study was to investigate the kinematics of the
      distal tibiofibular syndesmosis in intact and ligament injured ankles and to
      assess how effective is the syndesmotic screw in restraining mortise width
      variations during passive foot flexion. MATERIALS AND METHODS: The trials were
      carried out on seven fresh frozen cadaver specimens. The distal tibiofibular
      syndesmosis widening was investigated using Roentgen stereophotogrammetric
      analysis, in intact and ligament injured ankles and after the fixation of the
      syndesmotic screw. The AO-ASIF recommendations were followed for screw implant.
      RESULTS: Injury to the syndesmotic and deltoid ligaments of the ankle did not
      result in a significant variation of the syndesmosis behavior during passive foot
      flexion. The 4.5-mm diameter cortical screw used in this study proved effective
      in restraining mortise width variation during foot flexion. The recorded mortise
      widening in the flexion arc extending from the neutral to the maximally
      dorsiflexed position was negligible in intact and ligament injured joints.
      CONCLUSION: The result does not endorse the recommendation of placing the foot in
      full dorsal flexion during screw implantation. The choice of screw fixation as a
      treatment for ankle syndesmosis disruption should be carefully evaluated.

PMID- 16568289
TI  - [Procalcitonin as an early marker of sepsis].
AB  - A 64-year-old male with an APC resistance (factor V mutation Leiden) and
      interrupted oral anticoagulation due to an erosive gastritis, was admitted to
      hospital for increasing dyspnoea. Transthoracic echocardiography revealed a
      floating thrombus via an open foramen ovale in both atria reaching both
      ventricles. Sonography showed multiple stage thrombosis of the left leg reaching
      to the V. femoralis superficialis. A few months previously, peripheral pulmonary
      artery embolization has been confirmed by scintigraphy. The patient was
      transferred to our hospital and underwent emergency surgery for closure of the
      atrial septum defect and thrombus removal. On the 4th postoperative day, the
      patient was transferred to the normal ward, however, on the 10th postoperative
      day, the patient developed a symptomatic transitory psychotic syndrome and became
      hypotensive before he was transferred to the ICU. Due to impaired oxygenation and
      the patient's history, a new pulmonary artery embolization was suspected. After
      ICU admission, the patient required increasing norepinephrine support and rapidly
      developed septic fever. However, serum procalcitonin was elevated and a computed
      tomography (skull, chest and abdomen) was performed for a focus search. Pulmonary
      artery embolism could be ruled out but an oval structure near to the ampulla
      recti (ca. 30 x 20 mm) was identified as an abscess and immediate abscess
      incision was performed. After surgery, the further course was characterized by a
      steep fall in vasopressor support and body temperature. The patient was
      transferred to the normal ward on the 2nd postoperative day. This case shows that
      procalcitonin allows early and reliable diagnosis of sepsis in patients with
      undefined shock.

PMID- 16568291
TI  - Human metabolism of arsenolipids present in cod liver.
AB  - We report results from the first investigation of the human metabolism of arsenic
      containing lipids (arsenolipids), significant arsenic constituents of some
      seafood products. Two male volunteers ingested canned cod liver and the arsenic
      metabolites in their urine were monitored by high-performance liquid
      chromatography inductively coupled plasma mass spectrometry over a 66-h period.
      Volunteer A consumed 85 g (wet mass) of cod liver containing a total of
      approximately 120 microg arsenic, 77% of which was present as arsenolipids, and
      volunteer B consumed 85 g (wet mass) of cod liver, 25% of which was present as
      arsenolipids, together with 20 g of cod liver oil, containing a total of about
      180 microg arsenic. The structures of the arsenolipids are currently unknown,
      whereas the majority of the non-lipid arsenic in the cod liver was identified as
      arsenobetaine, which was excreted unchanged. The arsenolipids were rapidly
      metabolised to water-soluble compounds and excreted in the urine; peak arsenic
      concentrations were recorded between 7 and 15 h (volunteer A) and between 6.5 and
      15 h (volunteer B), and by the end of the experiment about 90% of the ingested
      arsenic had been accounted for in the urine for both volunteers. The major
      arsenolipid metabolite was dimethylarsinate (DMA), constituting 73% (volunteer A)
      or 41% (volunteer B) of the total urinary arsenic, and most of the remaining
      arsenolipid-derived arsenic, constituting about 10% (volunteer A) and 5%
      (volunteer B), comprised four novel arsenic-containing fatty acids, namely oxo
      dimethylarsenopropanoic acid, thio-dimethylarsenopropanoic acid, oxo
      dimethylarsenobutanoic acid, and thio-dimethylarsenobutanoic acid. Unchanged
      arsenobetaine (15% for volunteer A and 51% for volunteer B) made up the remaining
      urinary arsenic together with trace quantities of other, mostly unknown,
      arsenicals. In a second experiment (volunteer A only), performed with pure cod
      liver oil, which contains only arsenolipids, DMA and the same four arsenic fatty
      acids were excreted in the urine. The study shows that arsenolipids in cod liver
      are bioavailable, and that they are quickly biotransformed to several water
      soluble arsenicals, the structures of which suggest that the native arsenolipids
      contain a dimethylarsine oxide moiety.

PMID- 16568288
TI  - Cortisol promotes survival and regeneration of axotomised retinal ganglion cells
      and enhances effects of aurintricarboxylic acid.
AB  - BACKGROUND: Neuroprotection is essential for repair processes after a traumatic
      insult in the central nervous system. We have demonstrated previously significant
      neuroprotective properties of the anti-apoptotic drug aurintricarboxylic acid in
      the model of axotomised retinal ganglion cells. Glucocorticoids are widely used
      to treat injuries of the nervous system. Due to the anti-inflammatory and
      microglia-inhibiting properties of glucocorticoids, we studied the
      neuroprotective effects of intravitreally administered cortisol after an optic
      nerve cut. METHODS: Ninety-eight adult Sprague-Dawley rats were used in this
      study. The optic nerve was cut intra-orbitally. Either vehicle or compound
      solution was injected intravitreally. Fluorescent dye was put onto the optic
      nerve stump to label retinal ganglion cells retrogradely. Retinal whole mounts
      were prepared 2 weeks after axotomy, and surviving retinal ganglion cells were
      counted. RESULTS: Two weeks after axotomy, up to 50+/-7% of all retinal ganglion
      cells survived if cortisol was injected into the eye compared with 17+/-5%
      survival if only vehicle solution was injected. The neuroprotective effects of
      aurintricarboxylic acid (43+/-5% survival) could be further enhanced if combined
      with cortisol (up to 61+/-5% survival). Regeneration of cut retinal ganglion cell
      axons into a peripheral nerve graft could also be enhanced by an intravitreal
      injection of cortisol (169+/-42 regenerating retinal ganglion cells per mm2 vs.
      73+/-12 cells per mm2 after vehicle injection). The increase was not as high as
      with aurintricarboxylic acid (192+/-40 cells per mm2), although more retinal
      ganglion cells survived with cortisol. This indicates that neuronal survival
      alone is not sufficient for subsequent axonal regeneration. Nevertheless,
      regeneration could be markedly increased if aurintricarboxylic acid and cortisol
      were combined (308+/-72 cells per mm2). CONCLUSIONS: Whereas aurintricarboxylic
      acid seems to act directly on lesioned retinal ganglion cells, cortisol seems to
      act on the glial environment, as indicated by microglial cell morphology and
      enhanced glial fibrillary acidic protein expression. The results show that both
      neuroprotection and regeneration can be enhanced by the combination of two simple
      compounds acting on different sites.

PMID- 16568292
TI  - Trace-level determination of pharmaceutical residues by LC-MS/MS in natural and
      treated waters. A pilot-survey study.
AB  - A pilot-survey study was performed by collecting samples (influent and effluent
      wastewaters, rivers and tap waters) from different locations in Europe (Spain,
      Belgium, Germany and Slovenia). A solid-phase extraction (SPE) followed by liquid
      chromatography-tandem mass spectrometry method was applied for the determination
      of pharmaceuticals (ibuprofen, naproxen, ketoprofen, diclofenac and clofibric
      acid). Method detection limits and method quantification limits were at the parts
      per-trillion level (7.5-75 ng/L). The recovery rates of the SPE from deionized
      water and effluent wastewater samples spiked at 100- and 1,000-ng/L levels ranged
      from 87 to 95%. Identification criteria in compliance with the EU regulation for
      confirmatory methods of organic residues were applied. A detailed study of signal
      suppression evaluation for analysis of pharmaceutical residues in effluent
      wastewaters is presented.

PMID- 16568293
TI  - Modified superheated water extraction of pesticides from spiked sediment and
      soil.
AB  - In this study a laboratory-made superheated water system was applied in order to
      extract some pesticides from sand, sediment and soil samples. Extraction
      efficiencies were investigated at different time intervals with regard to
      temperature, type and amount of organic modifier. Pesticides were removed from
      the aqueous extract using dichloromethane as a trapping solvent. The optimal
      extraction temperature from sand specimens for malathion, heptachlor, aldrin,
      dieldrin, butachlor, metalaxyl and propiconazole was found to be 160 degrees C,
      while those for chlordane and thiobencarb were 120 degrees C and 180 degrees C,
      respectively. The static extraction time for heptachlor, aldrin, dieldrin,
      butachlor and metalaxyl was found to be 15 min, whereas for malathion and
      thiobencarb it was 5 min, and for chlordane and propiconazole it was 10 and 20
      min, respectively. Recoveries for the extractions of the pesticides from sand
      under optimized extraction conditions ranged between 96 and 101%. Those obtained
      from sediment under such conditions were unsatisfactory, and were consequently
      improved by adding an organic modifier to the superheated water, and sodium
      chloride to the extract during liquid-liquid extraction. These procedures were
      optimized further for the parameters described and recoveries exceeded 91%, with
      the exception of butachlor. The extraction technique was also applied to soil
      samples at a reduced water flow rate of 0.5 mL min(-1), yielding recoveries of 82
      105%, and 76% for dieldrin. The reproducibilities, expressed as relative standard
      deviations (RSDs), ranged between 2 and 13%.

PMID- 16568294
TI  - Biosensors based on carbon nanotubes.
AB  - Carbon nanotubes (CNTs) exhibit a unique combination of excellent mechanical,
      electrical and electrochemical properties, which has stimulated increasing
      interest in the application of CNTs as components in (bio)sensors. This review
      highlights various design methodologies for CNT-based biosensors and their
      employment for the detection of a number of biomolecules. In addition, recent
      developments in the fields of CNT-based chemiresistors and chemically sensitive
      field-effect transistors are presented. After a critical discussion of the
      factors that currently limit the practical use of CNT-based biosensors, the
      review concludes with an outline of potential future applications for CNTs in
      biology and medicine.

PMID- 16568295
TI  - Cyst-like cortical tubers in patients with tuberous sclerosis complex: MR imaging
      with the FLAIR sequence.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is an inherited disorder
      characterized by the presence of cortical tubers, the majority of which are solid
      and show high signal on FLAIR images. Low-signal tubers are less frequent.
      OBJECTIVE: To evaluate cystic cortical tubers in patients with TSC on the basis
      of their appearance on FLAIR images. MATERIALS AND METHODS: MR examinations of 73
      patients were retrospectively reviewed and 17 children (aged 25 days to 12.3
      years) with a typical cyst-like tubers were selected for further analysis. The
      age of the patients, the number of lesions, and the shape and MR intensity were
      analyzed. RESULTS: Cyst-like cortical tubers were detected in 82% of children
      below 7 years of age and in 18% of those older then 7 years (P=0.00086). Most of
      the cystic lesions were of the shrunken type (72%), the expansile type being less
      frequently seen (28%). CONCLUSIONS: FLAIR images confirm the cystic character of
      some of the cortical tubers in TSC patients although the pathogenesis of cystic
      change is still unknown.

PMID- 16568296
TI  - Progressive pulmonary calcification in a child after orthotopic liver
      transplantation.
AB  - We present a case of progressive pulmonary calcification associated with
      prolonged respiratory insufficiency in a 2-year-old boy with a history of
      orthotopic liver transplantation. This case demonstrates the potentially
      progressive nature of pulmonary calcification and that it can present with
      respiratory insufficiency at a later period after transplantation than previously
      thought. We describe radiological findings and discuss established as well as
      plausible pathological mechanisms contributing to the development of
      calcifications in these patients.

PMID- 16568298
TI  - Differential diagnosis of mesiotemporal lesions: case report of neurosyphilis.

PMID- 16568297
TI  - Zygomycosis: the re-emerging fungal infection.
AB  - Invasive fungal infections are major medical complications in immunocompromised
      patients. The recent rise in the incidence of cancer and the increased use of
      newer medical treatment modalities, including organ transplantations, have
      resulted in growing numbers of highly immunosuppressed individuals. Although
      aspergillosis and candidiasis are among the most common invasive mycoses in such
      patients, there is evidence that the incidence of infectious diseases caused by
      Zygomycetes has risen significantly over the past decade. Patients with diabetes,
      malignancies, solid organ or bone marrow transplants, or iron overload and those
      receiving immunosuppressive agents, deferoxamine therapy, or broad-spectrum
      antimicrobial drugs are at highest risk for zygomycosis. This review details the
      emergence and importance of zygomycosis in current clinical practice and its
      manifestations and management. The etiologic species, pathogenesis and risk
      factors for zygomycosis are reviewed and updated. The clinical spectrum of
      zygomycosis is now broader, and it can be difficult to distinguish between
      mucormycosis and enthomophthoramycosis, both of which can manifest as disease
      ranging from a superficial infection to an angioinvasive infection with high
      mortality. Finally, the three-part treatment strategy (antifungal drugs, surgery,
      control of underlying diseases) is reviewed. Lipid formulations of amphotericin B
      are the antifungal agents of choice for treatment of zygomycosis. A novel
      antifungal triazole, posaconazole, has been developed and may become approved for
      treatment of zygomycosis. The clinical experience with adjunctive treatments like
      colony-stimulating factors, interferon-gamma, and hyperbaric oxygen therapy is
      still limited.

PMID- 16568299
TI  - In vivo basal ganglia volumetry through application of NURBS models to MR images.
AB  - Volumetry of basal ganglia (BG) based on magnetic resonance imaging (MRI)
      provides a sensitive marker in differential diagnosis of BG disorders. The non
      uniform rational B-spline (NURBS) surfaces are mathematical representations of
      three-dimensional structures which have recently been applied in volumetric
      studies. In this study, a volumetric evaluation of BG based on NURBS was
      performed in 35 right-handed volunteers. We aimed to compare and validate this
      technique with respect to manual MRI volumetry and evaluate possible side
      differences between these structures. Intra- and interobserver biases less than
      1.5% demonstrated the method's stability. The mean percentage differences between
      NURBS and manual methods were less than 1% for all the structures considered;
      however, the internal segments of the globus pallidus showed a mean percentage
      difference of about 1.7%. Rightward asymmetry was found for the caudate nucleus
      (mean+/-SD 3.20+/-0.20 cm(3) vs. 3.10+/-0.19 cm(3), P<0.001) for both its head
      (1.44+/-0.10 cm(3) vs. 1.41+/-0.09 cm(3), P<0.01) and its body/tail (1.73+/-0.11
      cm(3) and 1.68+/-0.12 cm(3), P<0.01), and for the globus pallidus (1.23+/-0.08
      cm(3) and 1.18+/-0.09 cm(3), P<0.001) for both the internal (0.33+/-0.05 cm(3)
      vs. 0.31+/-0.05 cm(3), P<0.01) and external (0.90+/-0.05 cm(3) vs. 0.86+/-0.05
      cm(3), P<0.001) segments. No volumetric side differences were found for the
      putamen (3.43+/-0.14 cm(3) vs. 3.39+/-0.17 cm(3), P>0.05). The rightward
      asymmetry of the BG may be ascribed to the predominant use of the right hand. In
      conclusion, NURBS is an accurate and reliable method for quantitative volumetry
      of nervous structures. It offers the advantage of giving a three-dimensional
      representation of the structures examined.

PMID- 16568300
TI  - Nitric oxide: a co-modulator of efferent peptidergic neurosecretory cells
      including a unique octopaminergic neurone innervating locust heart.
AB  - Our findings suggest that nitric oxide (NO) acts as peripheral neuromodulator in
      locusts, in which it is commonly co-localized with RF-like peptide in
      neurosecretory cells. We also present the first evidence for NO as a cardio
      regulator in insects. Putative NO-producing neurones were detected in locust pre
      genital free abdominal ganglia by NADPH-diaphorase histochemistry and with an
      antibody against NO synthase (NOS). With both methods, we identified the same 14
      somata in each examined ganglion: two dorsal posterior midline somata; six
      ventral posterior midline somata; and three pairs of lateral somata. A
      combination of NOS-detection methods with nerve tracing and transmitter
      immunocytochemistry revealed that at least 12 of these cells were efferent, of
      which four were identified as peptidergic neurosecretory cells with an antiserum
      detecting RFamide-like peptides. One of the latter was unequivocally identified
      as an octopaminergic dorsal unpaired median (DUM) neurone, which specifically
      projected to the heart ("DUM-heart"). Its peripheral projections revealed by axon
      tracing appeared as a meshwork of varicose endings encapsulating the heart. NOS
      like immunoreactive profiles were found in the heart nerve. NO donors caused a
      dose-dependent increase in heart rate. This cardio-excitatory effect was
      negatively correlated to resting heart rate and seemed to be dependent on the
      physiological state of the animal. Hence, NO released from neurones such as the
      rhythmically active DUM-heart might exert continuous control over the heart.
      Possible mechanisms for the actions of NO on the heart and interactions with
      other neuromodulators co-localized in the DUM-heart neurone (octopamine, taurine,
      RF-amide-like peptide) are discussed.

PMID- 16568301
TI  - In vivo light-microscopic documentation for primary calcification processes in
      the hermatypic coral Stylophora pistillata.
AB  - Skeletogenesis in the hermatypic coral Stylophora pistillata was studied by using
      the lateral skeleton preparative (LSP) assay, viz., a coral nubbin attached to a
      glass coverslip glued to the bottom of a Petri dish. Observations on tissue and
      skeletal growth were made by polarized microscopy and by using vital staining.
      The horizontal distal tissue edges developed thin transparent extensions of
      ectodermal and calicoblastic layers only. Four stages (I-IV) of skeletogenesis
      were observed at these edges, underneath the newly developed tissue. In stage I,
      a thin clear layer of coral tissue advanced 3-40 microm beyond the existing LSP
      peripheral zone, revealing no sign of spiculae deposition. At stage II, primary
      fusiform crystals (1 microm each) were deposited, forming a primary discontinuous
      skeletal front 5-30 microm away from the previously deposited skeleton. During
      stage III, needle-like crystals appeared, covering the primary fusiform crystals.
      Stage IV involved further lengthening of the needle-like crystals, a process that
      resulted in occlusion of the spaces between adjacent crystals. Calcification
      stages I-III developed within hours, whereas stage IV was completed in several
      days to weeks. Two basic skeletal structures, "scattered" and "laminar"
      skeletons, were formed, integrating the growth patterns of the needle-like
      crystals. High variation was recorded in the expression of the four calcification
      stages, either between different locations along a single LSP or between
      different preparations observed at the same diurnal time. All four skeletogenesis
      stages took place during both day and night periods, indicating that an intrinsic
      process controls S. pistillata calcification.

PMID- 16568302
TI  - Identification, content, and distribution of type VI collagen in bovine tendons.
AB  - Tendon composition changes according to differentiation, mechanical load, and
      aging. In this study, we attempted to identify, localize, and quantify type VI
      collagen in bovine tendons. Type VI collagen was identified by the
      electrophoretic behavior of the alpha chains and Western blotting, and by rotary
      shadowing. Type VI collagen was extracted from powdered tendon with three
      sequential 24-h extractions with 4 M guanidine-HCl. The amount of type VI
      collagen was determined by enzyme-linked immunosorbent assay for purely tensional
      areas and for the compressive fibrocartilage regions of the deep flexor tendon of
      the digits, for the corresponding fetal and calf tendons, and for the extensor
      digital tendon. The distal fibrocartilaginous region of the adult tendon was
      richer in type VI collagen than the tensional area, reaching as much as 3.3 mg/g
      (0.33%) of the wet weight. Calf tendons showed an accumulation of type VI at the
      fibrocartilage site. Immunocytochemistry demonstrated that type VI collagen was
      evenly distributed in the tensional areas of tendons but was highly concentrated
      around the fibrochondrocytes in the fibrocartilages. The results demonstrate that
      tendons are variable with regard to the presence and distribution of type VI
      collagen. The early accumulation of type VI collagen in the region of calf tendon
      that will become fibrocartilage in the adult suggests that it is a good marker of
      fibrocartilage differentiation. Furthermore, the distribution of type VI collagen
      in tendon fibrocartilage indicates that it organizes the pericellular environment
      and may represent a survival factor for these cells.

PMID- 16568303
TI  - Estradiol increases VEGF in human breast studied by whole-tissue culture.
AB  - Sex steroid exposure constitutes a risk factor for breast cancer, but little is
      known about the effects of sex steroids on the normal breast, largely because of
      the lack of convenient models. We have developed a method of culturing normal
      breast tissue ex vivo. We have applied this method to investigate the effects of
      estradiol and progesterone on the key angiogenic mediator, vascular endothelial
      growth factor (VEGF), in the breast. Whole breast tissue was obtained from
      routine reduction mammoplasty. Tissue biopsies were cultured in vitro for 1-3
      weeks, and the expression of luminal cytokeratin 18 was determined by
      immunohistochemistry. As an application, tissue biopsies were treated in vitro
      for 1 week with or without estradiol or estradiol and progesterone. Estrogen
      receptor, progesterone receptor, and Ki-67 were analyzed, and VEGF levels were
      examined by quantitative immunoassay and immunohistochemistry. Whole breast
      tissue was cultured ex vivo for 1 week with preserved morphology. Increased
      detachment of the luminal epithelium was observed after 2 weeks. Estradiol
      increased extracellular levels of VEGF in normal breast tissue biopsy medium. The
      addition of progesterone had neither stimulatory nor inhibitory effects on
      secreted VEGF. The method of whole breast tissue culturing thus provide a means
      by which to explore the biology of normal breast tissue. Our results suggest that
      estradiol exerts pro-angiogenic effects in normal breast by increasing levels of
      biologically active VEGF.

PMID- 16568304
TI  - Another option to treat Kummell's disease with cord compression.
AB  - The efficiency of short-segment fixation with transpedicle body augmenter (a
      titanium spacer with bone-ingrowth porous surface, TpBA) to treat Kummell's
      disease with cord compression (stage III) was retrospectively evaluated. No
      laminectomy or instrumentation reduction was done. Inclusion criteria included
      Frankel CDE, single-level within T10-L2. FU rate was 88%, i.e. 21 cases were
      included. Frankel function classification was 6E9D6C. Mean age was 72+/-8 years.
      F:M was 16:5. FU period was 48 M (range, 30-76 M). The hospitalization was 4.5+/
      2.2 days; operation time, 70.4+/-17.2 min; blood loss, 150+/-72 cc. Final Frankel
      class was 20E1D. Complications included two superficial infection and one
      pneumonia. Body height and kyphosis were all corrected significantly and well
      preserved at the final visit. No TpBA dislodgement or implant failure was noted;
      however, three cases developed new compression fractures. The clinical outcome
      showed 81% with P1 or P2 by Denis pain scale. This method can decompress spinal
      canal, maintain kyphosis correction and vertebral restoration, prevent implant
      failure, and attain good clinical results.

PMID- 16568305
TI  - Frameless stereotaxy in a transmandibular, circumglossal, retropharyngeal
      cervical decompression in a Klippel-Feil patient: technical note.
AB  - Frameless stereotaxy, while most commonly applied to intracranial surgery, has
      seen an increasing number of applications in spinal surgery. Its use in the spine
      has been described to a greater degree in posterior rather than anterior surgical
      approaches, presumably due to the relative paucity of anatomical landmarks
      appropriate for frameless stereotactic registration in the anterior spine. This
      technical note illustrates the previously undescribed, successful use of
      frameless stereotaxy to the transmandibular, circumglossal, retropharyngeal
      surgical approach in a patient with Klippel-Feil syndrome.

PMID- 16568306
TI  - Alterations of blood pressure in type 1 diabetic children and adolescents.
AB  - The aim of this study was to assess the association between metabolic control,
      microalbuminuria, and diabetic nephropathy with ambulatory blood pressure
      monitoring (ABPM) in normotensive individuals with type 1 diabetes mellitus (DM).
      ABPM was undertaken in 68 normotensive type 1 diabetic patients with a mean age
      of 14.4+/-4.2 years. Microalbuminuria was diagnosed on the basis of a urinary
      albumin excretion rate grater than 20 microg/min in two of the three 24-h urine
      collections. Hypertension (HT) frequency was greater in the microalbuminuric
      patients than normoalbuminuric patients (54 vs 17.54%, p=0.05) with ABPM.
      Microalbuminuric patients had a higher diastolic pressure burden than
      normoalbuminuric patients. There were no differences in systolic and diastolic
      dips between the two groups. Diastolic pressure loads in all periods showed a
      significant correlation with duration of diabetes, mean HbA1c from the onset of
      diabetes, and level of microalbuminuria. Nocturnal dipping was reduced in 41.2%
      of the patients. In the normoalbuminuric group 41.1% and in the microalbuminuric
      group 63.6% were nondippers. Our data demonstrate higher 24-h and daytime
      diastolic blood pressure load and loss of nocturnal dip in type 1 diabetic
      adolescents and children. High diastolic blood pressure burden in diabetic
      patients could represent a risk for nephropathy.

PMID- 16568307
TI  - Role of mitotic, pro-apoptotic and anti-apoptotic factors in human kidney
      development.
AB  - The expression pattern of mitotic Ki-67 and anti-apoptotic bcl-2 proteins, as
      well as apoptotic caspase-3 and p53 proteins, were investigated in the human
      mesonephros and metanephros of 5-9 week-old human conceptuses. Apoptotic cells
      were additionally detected using the terminal deoxynucleotidyl transferase (TdT)
      nick-end labelling (TUNEL) method. Between the 5th and 7th developmental weeks Ki
      67, caspase-3 and TUNEL-positive cells characterized all mesonephric structures,
      indicating importance of cell proliferation in the growth of the mesonephros and
      role of apoptosis in nephrogenesis. From the 7th week on, p53 and bcl-2 positive
      cells appeared in the mesonephros as well. Regressive changes in the mesonephros
      could be regulated by activation of p53, while bcl-2 could contribute to
      selective survival of some tubules giving rise to adult structures. In the early
      human metanephros (5-7 weeks), Ki-67 positive cells characterized all metanephric
      structures, indicating a role of cell proliferation in branching of the ureteric
      bud and in nephron formation. During the same period bcl-2, caspase-3 and TUNEL
      positive cells were found only in the metanephric mesenchyme and nephrons. Bcl-2
      protein probably protected nephrons from apoptosis, while caspase-3 protein
      controlled cell death in the mesenchyme. At later stages (7-9-weeks), appearance
      of p53-expressing cells could participate in further morphogenesis of the
      metanephric collecting system. The factors investigated had a spatially and
      temporally restricted pattern of appearance in developing kidneys. Changes in
      that pattern might lead to serious disturbances of kidney formation and function
      in early childhood.

PMID- 16568308
TI  - Papillary thyroid carcinoma presenting as a solitary soft tissue arm metastasis
      in an elderly hyperthyroid patient. Case report and review of the literature.
AB  - A case of papillary thyroid carcinoma (PTC) presenting as a solitary metastasis
      in the right arm muscle is described in an elderly hyperthyroid male patient. A 2
      cm nodule in the right bycipites muscle was found to be a papillary carcinoma of
      thyroid origin and a primary, 3.5-cm tumor was subsequently found in the left
      lobe of a hyperfunctioning gland due to toxic goiter. Both tumors were well
      differentiated PTC, follicular variant. No high grade features, nor
      extrathyroidal spread, nor regional lymph node metastases were found, but
      histology evidenced intrathyroidal vascular invasion. After radical surgery and
      radioiodine therapy, the patient is currently disease-free 4 years after
      diagnosis. This is the third reported case of PTC manifesting as a single soft
      tissue metastasis and the first associated with hyperthyroidism. Hematogenous
      spread of differentiated PTC is rare, although less unusual in PTC follicular
      variant. Histological vascular invasion, hypervascularity and increased blood
      flow in the hyperfunctioning thyroid gland might have facilitated the
      dissemination of malignant tumor cells through the bloodstream. Literature data
      indicate that PTC in elderly patients is increasing and is often clinically
      aggressive. Radical surgical and radiometabolic treatments are required also in
      this age group to improve clinical outcome.

PMID- 16568309
TI  - Deregulation of HMGA2 in an aggressive angiomyxoma with t(11;12)(q23;q15).
AB  - Aggressive angiomyxoma is a soft-tissue neoplasm with a predilection for the
      pelvic and perineal regions and a tendency to recur locally. Cytogenetic data on
      this tumor type are limited to five cases, three of which showed rearrangement of
      chromosomal bands 12q13-15. Molecular investigation of two of the tumors
      identified the HMGA2 gene as the target of the 12q rearrangements. However, the
      two previously analyzed tumors were different at the molecular level: in one, the
      rearrangement of 12q13-15 resulted in a fusion product, whereas, in the second
      case, the breakpoint was telomeric (3') to the HMGA2, leaving the gene intact
      although expressed in its entire length. To shed more light on the pathobiology
      of aggressive angiomyxoma and to investigate the molecular mechanisms behind the
      involvement of the HMGA2 gene in this tumor type (fusion transcript vs
      deregulated expression), we investigated, cytogenetically and with molecular
      techniques, one such tumor which presented a t(11;12)(q23;q15) as the sole
      karyotypic aberration. FISH analyses demonstrated no structural alteration of
      HMGA2 at the cytogenetic level; however, expression of the full-length gene was
      detected molecularly.

PMID- 16568310
TI  - Trichostatin A enhances the response of chemotherapeutic agents in inhibiting
      pancreatic cancer cell proliferation.
AB  - Pancreatic cancer is an aggressive neoplasia, and standard chemotherapies are by
      and large ineffective. The purpose of this work was to get a comprehensive
      preclinical study on the ability of anticancer drug combinations that best
      inhibit growth of pancreatic adenocarcinoma cells. We evaluated the in vitro
      growth inhibition of ten pancreatic cancer cell lines to gemcitabine and 5
      fluorouracil, newer generation cytotoxic agents (oxaliplatin, irinotecan),
      targeted therapy (gefitinib) and a histone deacetylase (HDAC) inhibitor
      (trichostatin A). Cells were treated with the single drug alone and all pairwise
      drug association. Our results demonstrate that TSA can effectively increase the
      drug sensitivity of all the cell lines studied. The association of TSA and
      irinotecan determines an increase in growth inhibition on the highest percentage
      of cell lines (80%). Our findings may represent an experimental basis for
      potential clinical application of HDAC inhibitors, in particular in association
      with drugs used in cancer clinical treatment, supporting the idea that HDAC
      inhibitors could act as sensitizers for chemotherapy.

PMID- 16568311
TI  - Effect of nitrite on a thermophilic, methanogenic consortium from an oil storage
      tank.
AB  - Samples from an oil storage tank (resident temperature 40 to 60 degrees C), which
      experienced unwanted periodic odorous gas emissions, contained up to 2,400/ml of
      thermophilic, lactate-utilizing, sulfate-reducing bacteria. Significant methane
      production was also evident. Enrichments on acetate gave sheathed filaments
      characteristic of the acetotrophic methanogen Methanosaeta thermophila of which
      the presence was confirmed by determining the PCR-amplified 16S rDNA sequence.
      16S rDNA analysis of enrichments, grown on lactate- and sulfate-containing media,
      indicated the presence of bacteria related to Garciella nitratireducens,
      Clostridium sp. and Acinetobacter sp. These sulfidogenic enrichments typically
      produced sulfide to a maximum concentration of 5-7 mM in media containing excess
      lactate and 10 mM sulfate or thiosulfate. Both the production of sulfide and the
      consumption of acetate by the enrichment cultures were inhibited by low
      concentrations of nitrite (0.5-1.0 mM). Hence, addition of nitrite may be an
      effective way to prevent odorous gas emissions from the storage tank.

PMID- 16568313
TI  - Monascus fermentation of dioscorea for increasing the production of cholesterol
      lowering agent--monacolin K and antiinflammation agent--monascin.
AB  - Monacolin K, an inhibitor for cholesterol synthesis, is the secondary metabolite
      of Monascus species. The formation of the secondary metabolites of the Monascus
      species is affected by cultivation environment and method. This research uses
      sweet potato (Ipomoea batatas), potato (Solanum tuberosum), casava (Manihot
      esculenta), and dioscorea (Dioscorea batatas) as the substrates and discusses the
      best substrate to produce monacolin K. The results show that Monascus purpureus
      NTU 301, with dioscorea as the substrate, can produce monacolin K at 2,584 mg kg(
      1), which is 5.37 times to that resulted when rice is used as the substrate. In
      addition, more amount of yellow pigment can be found in Monascus-fermented
      dioscorea than in Monascus-fermented rice. The certain composition of yellow
      pigment is identified as monascin, which has been shown as an antiinflammation
      agent exhibiting potent inhibitory effects on 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced inflammation in mice in previous studies. Therefore,
      dioscorea is concluded to be the best substrate for Monascus species to produce
      the cholesterol-lowering agent-monacolin K and antiinflammation agent-monascin.

PMID- 16568312
TI  - Suspended aggregates as an immobilization mode for high-density perfusion culture
      of HEK 293 cells in a stirred tank bioreactor.
AB  - Cells of the human embryonic kidney cell line (HEK 293) grown in repeated
      suspension and perfusion systems were characterized and described. Cell
      aggregates that formed immediately after the HEK 293 cells were inoculated in
      stirred vessels in serum-containing Dulbecco's modified Eagle's medium (D-MEM)/F
      12 medium. The mean diameter of the cell aggregates reflecting the aggregate size
      increased with culture time, shifting from 63 to 239 mum after 1 and 8 days of
      culture in spinner flasks, respectively. No significant differences in cell
      performance were observed between HEK 293 cell populations grown as suspended
      aggregates and those grown as anchored monolayers. Replacing the D-MEM/F-12 with
      CD 293 medium caused the compact spherical cell aggregates to dissociate into
      single cells and small irregular aggregates without any apparent effect on cell
      performance. Moreover, the spherical cell aggregates could reform from individual
      cells and small aggregates when exposed to the serum-containing D-MEM/F-12
      dominant medium. Perfusion culture of HEK 293 cells grown as suspended aggregates
      in a 7.5-l stirred tank bioreactor for 17 days resulted in a maximum viable cell
      density of 1.2 x 10(7) cells ml(-1). These results demonstrate the feasibility
      and proof-of-concept for using aggregates as an immobilization system in large
      scale stirred bioreactors because a small-scale culture can be used as easily as
      the inoculum for larger bioreactors.

PMID- 16568314
TI  - Purification and characterization of laccase produced by a white rot fungus
      Pleurotus sajor-caju under submerged culture condition and its potential in
      decolorization of azo dyes.
AB  - An extracellular laccase was isolated and purified from Pleurotus sajor-caju
      grown in submerged culture in a bioreactor, and used to investigate its ability
      to decolorize three azo dyes. The extracellular laccase production was enhanced
      up to 2.5-fold in the medium amended with xylidine (1 mM). Purification was
      carried out using ammonium sulfate (70% w/v), DEAE-cellulose, and Sephadex G-100
      column chromatography. The enzyme was purified up to 10.3-fold from the initial
      protein preparation with an overall yield of 53%. The purified laccase was
      monomeric with an apparent molecular mass of 61.0 kDa. The purified enzyme
      exerted its optimal activity with 2,2-azino-bis(3-ethylbenzo-thiazoline-6
      sulfonate (ABTS) and oxidized various lignin-related phenols. The catalytic
      efficiencies kcat/Km determined for ABTS and syringaldazine were 9.2x10(5) and
      8.7x10(5), respectively. The optimum pH and temperature for the purified enzyme
      was 5.0 and 40 degrees C, respectively. Sodium azide completely inhibited the
      laccase activity. The absorption spectrum revealed type 1 and type 3 copper
      signals. The purified enzyme decolorized azo dyes such as acid red 18, acid Black
      1, and direct blue 71 up to 90, 87, and 72%, respectively. Decolorization ability
      of P. sajor-caju laccase suggests that this enzyme could be used for
      decolorization of industrial effluents.

PMID- 16568315
TI  - Biological function of the pld gene product that degrades epsilon-poly-L-lysine
      in Streptomyces albulus.
AB  - Epsilon-poly-L-lysine (epsilon-PL) is one of the few naturally occurring
      biopolymers and is characterized by a peptide bond between the alpha-carboxyl and
      epsilon-amino groups. Previously, we purified and characterized the epsilon-PL
      degrading enzyme (Pld) from Streptomyces albulus, which is an epsilon-PL
      producer, and this enzyme was expected to confer self-resistance to the epsilon
      PL produced by the organism itself. The gene encoding Pld was cloned based on the
      N-terminal amino acid sequence determined in this study, and a sequencing
      analysis revealed eight open reading frames (ORFs), i.e., ORF1 to ORF8 in the
      flanking region surrounding the pld gene (present in ORF5). To investigate the
      biological function of Pld, we constructed a knockout mutant in which the pld
      gene is inactivated. Studies on epsilon-PL susceptibility, epsilon-PL-degrading
      activity, and epsilon-PL productivity demonstrated that the pld gene does play a
      partial role in self-resistance and that S. albulus was found to produce other
      epsilon-PL-degrading enzyme(s) in addition to Pld. To the best of our knowledge,
      this is the first report on a self-resistance gene for a biopolymer possessing
      antibacterial activity.

PMID- 16568316
TI  - Systems for the detection and analysis of protein-protein interactions.
AB  - The analysis of protein-protein interactions is important for developing a better
      understanding of the functional annotations of proteins that are involved in
      various biochemical reactions in vivo. The discovery that a protein with an
      unknown function binds to a protein with a known function could provide a
      significant clue to the cellular pathway concerning the unknown protein.
      Therefore, information on protein-protein interactions obtained by the
      comprehensive analysis of all gene products is available for the construction of
      interactive networks consisting of individual protein-protein interactions,
      which, in turn, permit elaborate biological phenomena to be understood. Systems
      for detecting protein-protein interactions in vitro and in vivo have been
      developed, and have been modified to compensate for limitations. Using these
      novel approaches, comprehensive and reliable information on protein-protein
      interactions can be determined. Systems that permit this to be achieved are
      described in this review.

PMID- 16568317
TI  - Production and partial characterization of arabinoxylan-degrading enzymes by
      Penicillium brasilianum under solid-state fermentation.
AB  - The production of a battery of arabinoxylan-degrading enzymes by the fungus
      Penicillium brasilianum grown on brewer's spent grain (BSG) under solid-state
      fermentation was investigated. Initial moisture content, initial pH, temperature,
      and nitrogen source content were optimized to achieve maximum production of
      feruloyl esterase, xylanase, and alpha-L: -arabinofuranosidase. Under the optimum
      growth conditions (80% moisture, pH 6, 26.5 degrees C, and 5 g/l nitrogen
      source), the maximum level of feruloyl esterase (1,542 mU/g BSG) was found after
      196 h, whereas xylanase (709 U/g BSG) and ArabF activity (3,567 mU/g BSG) were
      maximal after 108 h and 96 h, respectively. Based on substrate utilization data,
      the feruloyl esterases produced by P. brasilianum was anticipated to subclass B.
      A crude enzyme (CE) preparation from P. brasilianum culture grown on BSG was
      tested for the release of hydroxycinnamic acids and pentoses from BSG. The P.
      brasilianum CE produced in this work contains a balance of cell wall-modifying
      enzymes capable of degrading arabinoxylan of BSG by more than 40%.

PMID- 16568318
TI  - Autecological properties of soil sphingomonads involved in the degradation of
      polycyclic aromatic hydrocarbons.
AB  - Autecological properties that are thought to be important for polycyclic aromatic
      hydrocarbon (PAH)-degradation by bacteria in contaminated soils include the
      ability to utilize a broad range of carbon sources, efficient biofilm formation,
      cell-surface hydrophobicity, surfactant production, motility, and chemotaxis.
      Sphingomonas species are common PAH-degraders, and a selection of PAH-degrading
      sphingomonad strains isolated from contaminated soils was therefore characterized
      in terms of these properties. All the sphingomonads tested were relatively
      hydrophilic and were able to grow as biofilms on a phenanthrene-coated surface,
      though biofilm formation under other conditions was variable. Sphingobium
      yanoikuyae B1 was able to utilize the greatest range of carbon sources, though it
      was not chemotaxic towards any of the substrates tested. Other sphingomonad
      strains were considerably less flexible in their catabolic range. None of the
      strains produced detectable surfactant and swimming motility varied between the
      strains. Examination of the total Sphingomonas community in the soils tested
      showed that one of the isolates studied was present at significant levels,
      suggesting that it can thrive under PAH-contaminated conditions despite the lack
      of many of the tested characteristics. We conclude that these properties are not
      essential for survival and persistence of Sphingomonas in PAH-contaminated soils.

PMID- 16568319
TI  - Von Willebrand factor and thrombosis.
AB  - There is increasing evidence that von Willebrand factor (VWF), an adhesive
      multimeric protein that has an important function in primary hemostasis and as a
      carrier of factor VIII, has a pivotal role in thrombogenesis. In fact, while the
      presence in plasma of unusually large VWF multimers due to a congenital or
      acquired deficiency of a VWF-cleaving metalloprotease has been implicated in the
      pathogenesis of thrombotic thrombocytopenic purpura (TTP), high plasma levels of
      VWF have been associated with a slightly increased risk of arterial thrombosis.
      With regard to the association between VWF and venous thrombosis, clear
      conclusions cannot yet be drawn from the conflicting published data. Patients
      with von Willebrand disease, an inherited hemorrhagic disorder, may also
      paradoxically experience thrombotic events as a result of interactions among
      multiple prothrombotic risk factors. After a description of the structure and
      physiology of VWF, all these aspects are discussed in the present review.

PMID- 16568320
TI  - Myelodysplastic patients with raised percentage of hypochromic red cells have
      evidence of functional iron deficiency.
AB  - Raised percentage hypochromic red cells (%HRC) were detected at diagnosis in 10
      of 34 consecutive patients with low-risk myelodysplastic syndrome (MDS)
      [refractory anemia (RA) (4/26) and RA with ring sideroblasts (6/8)], all of whom
      had normal or increased serum ferritin and bone marrow iron stores. Elevated %HRC
      has persisted in all 10 cases and subsequently developed in another RA patient
      who later had a complete remission of MDS with normalisation of %HRC after a
      respiratory tract infection. A strong positive correlation was found between %HRC
      and erythrocyte zinc protoporphyrin levels in 11 MDS patients tested (p=0.01),
      suggesting that functional iron deficiency contributes to ineffective
      erythropoiesis in cases of MDS with raised %HRC. Five of seven patients with
      elevated %HRC had satisfactory haemoglobin responses to a trial of human
      recombinant erythropoietin without iron supplementation.

PMID- 16568321
TI  - Primary pancreatic lymphoma--a rare cause of cholestasis leading to surgical
      treatment.

PMID- 16568324
TI  - "Fibrinolytic capacity in peritoneal fluid after laparoscopic and conventional
      colorectal resection: data from a randomized controlled trial" by J. Neudecker et
      al.

PMID- 16568325
TI  - The vagal nerve as a link between the nervous and immune system in the instance
      of polymicrobial sepsis.
AB  - BACKGROUND: The role of the vagal nerve in the autonomic nervous system is widely
      well known. Recently, an additional function was revealed serving as a connector
      between the nervous and immune system. This connection is called the "cholinergic
      inflammatory pathway." Through stimulation of the acetylcholine receptors located
      upon the macrophages, the "unspecific" immune system can be directly influenced.
      METHODS: The vagal nerve was completely transected directly posterior to its
      passage through the diaphragm. The effect of complete vagotomy was analyzed using
      a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis,
      CASP). Survival and clinical course of vagotomized or sham-operated mice were
      analyzed in the CASP model. RESULTS: After CASP surgery, vagotomy led to a
      significantly increased mortality (64.7%) in comparison to sham-vagotomized
      animals (34%). No difference in the bacterial load of various tissues (lung,
      liver, spleen, blood, lavage fluid, and kidney) from septic animals with or
      without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine
      levels (TNF, IL-6, IL-10, and MCP-1) 20 h after the induction of polymicrobial
      peritonitis. CONCLUSION: The vagal nerve is therefore an important modulator of
      the immune system.

PMID- 16568326
TI  - Octreotide hardens the pancreas.
AB  - BACKGROUND AND AIMS: Leakage from pancreaticojejunostomy and development of
      pancreatic fistulas are the major postoperative complications in patients
      undergoing duodenopancreatectomy. The risk of developing these complications is
      higher when surgery is performed on a soft pancreas. A recent report suggests
      that octreotide hardens the pancreas when given intraoperatively. The present
      study aims at verifying this observation by measuring tissue hardness of the
      pancreas by a commercially available durometer in pigs with and without
      octreotide pretreatment. METHODS: Three groups of pigs were investigated: Group 1
      (n=6) received no treatment; group 2 (n=6) was treated with 3x100 microg
      octreotide for 1 day; group 3 (n=6) for 5 days. Thereafter, animals were killed
      and the pancreas was harvested for performing measurements: Tissue hardness was
      assessed by a commercially available durometer, and a suture holding test was
      performed using a Newton dynamometer. RESULTS: There was a significant increase
      in tissue hardness between untreated control animals [26.3+/-2.5 S.U. (shore
      units)] and animals with 1 day octreotide pretreatment (29.8+/-2.6 S.U.; p=0.04)
      as well as between the groups treated for 1 and 5 days (34.8+/-2.8 S.U.; p=0.01).
      Suture holding capacity was higher in animals treated for 5 days. CONCLUSION: The
      present study agrees with a recent report suggesting that octreotide hardens the
      pancreas. Octreotide pretreatment may therefore be an advantage when performing
      surgery on a soft pancreas, i.e., in patients scheduled for duodenopancreatectomy
      for ampullary carcinomas or circumscript pancreatic tumors not associated with
      chronic pancreatitis.

PMID- 16568327
TI  - Blood loss in total knee arthroplasty: an analysis of risk factors.
AB  - The amount of blood loss in a primary cemented total knee arthroplasty (TKA)
      seems to vary in different reported studies. We carried out a prospective study
      to determine the factors affecting the peri-operative blood loss, hidden blood
      loss and blood transfusion requirements in a primary cemented total knee
      arthroplasty. The factors analysed were gender, diagnosis, tourniquet time and
      body mass index (BMI). We included a total of 66 consecutive patients who
      underwent primary TKA by a single surgeon (A.M). There was significantly more
      peri-operative blood loss in male patients than in females (p=0.001, Student's t
      test). The patients with rheumatoid arthritis did not show any statistical
      difference in peri-operative blood loss compared with that in patients with
      osteoarthritis. The tourniquet time and the surgical time showed a positive
      correlation with peri-operative blood loss. The BMI did not show any correlation
      with peri-operative blood loss. The incidence of blood transfusion was
      significantly higher in patients with rheumatoid knees as their pre-operative
      haemoglobin value was low. The amount of hidden blood loss in our series was 38%.
      We concluded that gender and tourniquet time plays a role in blood loss in TKA,
      but diagnosis (advanced osteoarthritis [OA] or rheumatoid arthritis (RA) does
      not. The blood transfusion depends on both pre-operative haemoglobin value and
      intra-operative blood loss. The post-operative transfusion trigger can be brought
      to 8.0 g% in a haemodynamically stable patient.

PMID- 16568328
TI  - Treatment of open tibial shaft fractures using tightly fitted interlocking
      nailing.
AB  - Between 2000 and 2003 we treated 23 patients who sustained open tibial shaft
      fractures with tightly fitted interlocking intramedullary nailing. There were
      three grade I, eight grade II, nine grade IIIa, and three grade IIIb open
      fractures. Nail diameters were decided on using preoperative and intraoperative
      radiographs. Nails were introduced after gentle passage with a 7- to 8-mm hand
      reamer. Union was obtained in all cases. Nine (37.5%) fractures, however,
      required additional procedures before union. Three of them gained union through
      exchange nailing, bone graft, and bone transport, respectively. The remaining six
      underwent dynamisation. Two of them required an additional exchange nailing for
      non-union; thereafter one healed and the other gained union through an additional
      bone graft. Deep infection occurred in one case. Screw breakage occurred in one
      case only. Tightly fitted nailing produced a significantly lower incidence of
      locking screw breakage. However, even with this advantage, this technical
      modification has failed to show clinical advantage in terms of higher healing
      rate or lower rate of secondary procedures.

PMID- 16568329
TI  - Reducing incision length or intensifying rehabilitation: what makes the
      difference to length of stay in total hip replacement in a UK setting?
AB  - Minimal-incision surgery for hip arthroplasty and intensive post-op physiotherapy
      have both been shown to allow early mobilisation and to reduce hospital stay.
      Forty-five patients undergoing primary total hip arthroplasty using a standard
      posterior approach were compared with 51 patients using a minimal incision. In
      both groups, physiotherapy involved either a routine or intensive regime.
      Patients were matched in age, sex and body mass index. There was no significant
      difference in blood loss, post-operative stay and change in Oxford hip scores at
      one year between the mini- and standard-incision groups. There was a significant
      difference (P=0.003) in length of stay between routine- and intensive
      physiotherapy groups (11.4 vs. 7.9 days). The dislocation rate was higher in the
      mini-incision group. This study suggests that in a standard UK setting, intensive
      physiotherapy can significantly decrease in-patient stay, but reducing the
      incision length does not.

PMID- 16568330
TI  - Two-stage surgical procedure for treating pelvic malunions.
AB  - When surgically treated, pelvic-ring deformities due to post-traumatic malunions
      in adults usually require invasive three-stage (prone/supine/prone or
      supine/prone/supine) procedures. A standardised two-stage prone/supine procedure
      was developed by the authors. Technical points and first clinical results are
      presented. Malunuions related to Tile B and C types of fracture were successfully
      corrected.

PMID- 16568331
TI  - Phenotypic comparison of allopatric populations of Fasciola hepatica and Fasciola
      gigantica from European and African bovines using a computer image analysis
      system (CIAS).
AB  - The quantification of the different sizes and shapes of Fasciola hepatica and
      Fasciola gigantica from bovines has been achieved for the first time in natural
      allopatric populations. Linear measurements, areas and ratios of gravid adults
      and eggs of F. hepatica (from France and Spain) and F. gigantica (from Burkina
      Faso) were analysed using a computer image analysis system and an allometric
      model: (y2m - y2)/y2 = c[(y1m - y1)/y1](b), where y1 = body area or body length,
      y2 = one of the measurements analysed, y1m, y2m = maximum values towards which y1
      and y2, respectively, tend and c, b = constants. All the measurements overlap in
      the two fasciolids, apart from the distance between the ventral sucker and the
      posterior end of the body, body roundness and body length/body width ratio. The
      results obtained may be useful in Fasciola species identification in countries
      where both species coexist.

PMID- 16568332
TI  - An ultrastructural study of alimentary tract development in the cercariae of
      Diplostomum pseudospathaceum (Digenea: Diplostomidae).
AB  - Morphogenesis of the alimentary canal in developing Diplostomum pseudospathaceum
      cercariae has been studied using electron microscopy. The foregut primordium
      appears in early cercariae as a cellular cord. Later, the lumen develops within
      the foregut primordium, and its cells give rise to the cellular epithelium,
      limiting this lumen. During subsequent development, the lateral plasma membranes,
      separating the cells, disappear from the primary foregut epithelium as do nuclei
      and most of cellular organelles. These events seem to progress in several steps,
      and eventually, the foregut lining becomes the thin anucleate syncytial layer. In
      late cercariae, this layer becomes connected with nucleated cytons, producing
      secretory inclusions. Each of two caecal branches appears to arise from a row of
      large cuboid cells. The primordial gastrodermal cells are involved in synthetic
      and secretory activity and give rise to numerous secretory inclusions. These
      inclusions release their contents into the cavities which develop between
      adjacent primordial caecal cells. The intercellular cavities gradually increase
      in size and fuse to eventually form a single caecal lumen. In mature cercariae,
      the large caecal lumen packed with electron-dense secretory material is limited
      by a thin cellular gastrodermis, displaying no secretory features.

PMID- 16568333
TI  - Reliability of microbial surrogate Chlorella for determining Cryptosporidium
      oocysts removal.
AB  - The green alga, Chlorella, abundant in water sources and similar in size to the
      Cryptosporidium oocysts, may be a suitable candidate to evaluate the removal
      capacities of the waterworks for Cryptosporidium oocysts. The zeta potentials of
      Cryptosporidium oocysts in different water samples were more negative than
      Chlorella. Although the hydrophobicities of Chlorella were similar to
      Cryptosporidium oocysts, the experimental collision efficiencies for
      Cryptosporidium oocysts were higher than for Chlorella. It is indicated that
      Cryptosporidium oocysts would consume more coagulants during coagulation, with
      higher removal rate in the filtration process than Chlorella.

PMID- 16568335
TI  - [Oral submucous fibrosis in a 31-year-old Indian women: first case report from
      Germany].
AB  - BACKGROUND: Oral submucous fibrosis (OSF) is a chronic disease characterized by
      subepithelial collagen deposition with formation of bands involving the oral
      cavity and adjacent structures. Oral submucous fibrosis is a precancerous
      condition. It is caused by chewing of betel quid (Areca catechu L., Piper betle,
      lime and tobacco) and ready-made products like pan masala and gutka which also
      contain areca nut. These products are available all over South Asia. The hallmark
      of OSF is extremely restricted mouth opening. CASE REPORT: A 31-year-old Indian
      woman who has lived in Germany since 1997 presented herself because of limitation
      of mouth opening. She reported that she has chewed pan masala and gutka since she
      was 17 years of age. History, clinical and histological findings clearly pointed
      to the diagnosis of OSF. DISCUSSION: Conservative as well as surgical
      interventions for OSF have not resulted in adequate long-term results. Since OSF
      may occur in children and young adults, the primary aim should be to avoid
      progression of the disease, initially by physiotherapy. Surgical interventions
      should not be applied at an early stage of the disease because recurrences and
      further surgical interventions are often necessary. Due to the increasing numbers
      of migrants from South Asia more cases of OSF will probably also be observed in
      Germany, where areca nut-containing products are also available.

PMID- 16568334
TI  - A new shampoo based on neem (Azadirachta indica) is highly effective against head
      lice in vitro.
AB  - Because topical compounds based on insecticidal chemicals are the mainstay of
      head lice treatment, but resistance is increasing, alternatives, such as herbs
      and oils are being sold to treat head lice. To test a commercial shampoo based on
      seed extract of Azadirachta indica (neem tree) for its in vitro effect, head lice
      (n=17) were collected from school children in Australia and immersed in Wash-Away
      Louse shampoo (Alpha-Biocare GmbH, Germany). Vitality was evaluated for more than
      3 h by examination under a dissecting microscope. Positive and negative controls
      were a commercially available head lice treatment containing permethrin 1% (n=19)
      and no treatment (n=14). All lice treated with the neem shampoo did not show any
      vital signs from the initial examination after immersion at 5-30 min; after 3 h,
      only a single louse showed minor signs of life, indicated by gut movements, a
      mortality of 94%. In the permethrin group, mortality was 20% at 5 min, 50% at 15
      min, and 74% after 3 h. All 14 head lice of the negative control group survived
      during the observation period. Our data show that Wash-Away Louse is highly
      effective in vitro against head lice. The neem shampoo was more effective than
      the permethrin-based product. We speculate that complex plant-based compounds
      will replace the well-defined chemical pediculicides if resistance to the
      commonly used products further increases.

PMID- 16568336
TI  - Arbuscular mycorrhizal status of spring ephemerals in the desert ecosystem of
      Junggar Basin, China.
AB  - A survey was made of the arbuscular mycorrhizal (AM) status of 73 spring
      ephemeral plant species that grow in the desert ecosystem of Junggar Basin,
      northwest China. The proportion of AM colonization ranged from 7 to 73% with a
      mean value of 30%. A total of 65 plant species studied were AM with
      coils/arbuscules or vesicles and the remaining eight species were possibly AM
      with no coils/arbuscules or vesicles but with fungal mycelia in the root cortex.
      AM fungal spores were isolated from rhizosphere samples of all 73 plant species
      and identified. The mean spore density was 22 per 20 ml of air-dried soil,
      ranging from 0 to 120. Colonization and spore density of perennials were slightly
      higher than of annuals and varied among different plant families. A total of 603
      AM fungal spore (or sporocarp) specimens were isolated belonging to six genera,
      Acaulospora, Archaeopora, Entrophospora, Glomus, Paraglomus, and Scutellospora;
      Glomus was the dominant genus. We conclude that spring ephemerals may be highly
      dependent on AM associations for survival in the very infertile and arid soils of
      this desert ecosystem.

PMID- 16568338
TI  - The effect of unilateral and bilateral strength training on the bilateral deficit
      and lean tissue mass in post-menopausal women.
AB  - Some have observed maximal strength of simultaneous bilateral homologous limb
      contraction is less than the sum of strengths of right and left limbs contracting
      alone; a phenomenon referred to as the bilateral deficit (BLD). There is
      controversy on whether there is a BLD for all exercises. We assessed whether a
      BLD occurs across different exercises (leg press, knee extension, and lat pull
      down), whether the BLD could be altered with unilateral or bilateral training,
      and whether unilateral versus bilateral training was more beneficial for
      increasing lean tissue mass (LTM). Post-menopausal women (approximately 57 years)
      were randomized to bilateral (n=14) and unilateral (n=12) training, or non
      training control (n=24) groups. Bilateral training involved seven exercises
      performed with bilateral contractions (two sets, 3 days week-1, 26 weeks).
      Unilateral training involved the same exercises performed with one limb at a
      time. A BLD was found for leg press and lat pull-down, but not for knee
      extension. Bilateral training decreased the BLD; whereas unilateral training had
      minimal effect on the BLD. The unilateral-training group had a greater increase
      in lower-body LTM compared to the control group (P<0.05); however, there were no
      differences between unilateral and bilateral training groups. Both training
      groups had greater increases in LTM of the upper- and whole-body compared to the
      control group. We conclude that the BLD is apparent for some exercises (i.e., the
      leg press and lat pull-down) but not others (i.e., knee extension). Bilateral
      training reduces the BLD; whereas unilateral training has minimal effect on the
      BLD.

PMID- 16568337
TI  - Single nucleotide polymorphism, genetic mapping, and expression of genes coding
      for the DOF wheat prolamin-box binding factor.
AB  - Wheat prolamin-box binding factor (WPBF) was shown to be an activator of Triticum
      aestivum L. storage protein genes. Three homoeologous genes encoding this
      transcription factor were isolated from a bacterial artificial chromosome genomic
      library and sequenced. The genes all have two exons separated by an intron of
      approximately 1,000 bp where the second exon contains the entire coding sequence.
      Many differences were found between homoeologous sequences, but none of them is
      predicted to significantly alter the sequence of the putative encoded protein.
      The three homoeologous genes are specifically expressed in grain from 3 to 39
      days after anthesis. The allelic variation of a genetically diverse collection of
      27 bread wheat lines was assessed. One, five, and one single-nucleotide
      polymorphisms (SNPs) were detected in the wPbf genes for the A, B, and D genomes,
      respectively. Physical and genetic mapping utilizing some of the SNPs identified
      confirmed that wPbf genes are located close to the centromeres on the
      homoeologous group 5 chromosomes. The low level of allelic diversity found in
      wPbf genes may suggest that these genes play a key role and are thus constrained
      by selection.

PMID- 16568339
TI  - Increase of adiponectin receptor gene expression by physical exercise in soleus
      muscle of obese Zucker rats.
AB  - Aerobic exercise, including treadmill running has been widely used to treat
      insulin resistance and type 2 diabetes. We studied the effects of endurance
      training on gene expression of adiponectin receptor 1 (AdipoR1) in skeletal
      muscle of obese Zucker rats: the 8-week moderate exercise program consisted of
      treadmill running at 20 m/min and 0 degrees gradient for 1 h/day, 7 days/week.
      After 8 weeks, insulin action on glucose disposal rate was measured by glucose
      insulin index, the product of the areas under the curve of glucose and insulin
      during intraperitoneal glucose tolerance testing. In contrast to results for
      sedentary obese rats, exercise training decreased plasma levels of insulin and
      glucose as well as the glucose-insulin index in obese rats, indicating the merit
      of regular moderate exercise for improvement of insulin sensitivity in this
      insulin-resistant animal model. Also, diabetes-related reductions in mRNA and
      protein content of AdipoR1 in soleus muscle were observed in obese rats at
      baseline; they were markedly reversed after the 8-week exercise program. However,
      such exercise training did not alter plasma levels of insulin and glucose in lean
      Zucker rats. Also, AdipoR1 gene expression in soleus muscle was not changed by
      exercise in lean Zucker rats compared with the sedentary, lean littermates. These
      results suggest that long-term exercise training may reverse reduced AdipoR1 gene
      expression in soleus muscle and improve insulin sensitivity in the obese Zucker
      rats. Thus, an endurance exercise training is probably helpful clinically for
      obese individuals with insulin resistance.

PMID- 16568340
TI  - Human skeletal muscle structure and function preserved by vibration muscle
      exercise following 55 days of bed rest.
AB  - Prolonged immobilization of the human body results in functional impairments and
      musculoskeletal system deconditioning that may be attenuated by adequate muscle
      exercise. In a 56-day horizontal bed rest campaign involving voluntary males we
      investigated the effects of vibration muscle exercise (RVE, 2x6 min daily) on the
      lower limb skeletal muscles using a newly designed foot plantar trainer (Galileo
      Space) for use at supine position during bed rest. The maximally voluntary
      isometric plantar flexion force was maintained following regular RVE bouts during
      bed rest (controls -18.6 %, P<0.05). At the start (BR2) and end of bed rest
      (BR55) muscle biopsies were taken from both mixed fast/slow-type vastus lateralis
      (VL) and mainly slow-type soleus muscle (SOL), each having n=10. RVE group: the
      size of myofiber types I and II was largely unchanged in VL, and increased in
      SOL. Ctrl group: the SOL depicted a disrupted pattern of myofibers I/II profiles
      (i.e., type II>140 % vs. preBR) suggesting a slow-to-fast muscle phenotype shift.
      In RVE-trained SOL, however, an overall conserved myofiber I/II pattern was
      documented. RVE training increased the activity-dependent expression of nitric
      oxide synthase type 1 immunofluorescence at SOL and VL myofiber membranes. These
      data provide evidence for the beneficial effects of RVE training on the
      deconditioned structure and function of the lower limb skeletal muscle. Daily
      short RVE should be employed as an effective atrophy countermeasure co-protocol
      preferentially addressing postural calf muscles during prolonged clinical
      immobilization or long-term human space missions.

PMID- 16568341
TI  - Proximal tibia medial open-wedge osteotomy using plates with wedges: early
      results in 58 cases.
AB  - We evaluated in this study indications, surgical technique, and results of wedge
      plates for fixation in proximal tibia medial opening wedge osteotomy. Fifty-eight
      knees in 56 consecutive patients (9 men, 47 women; mean age 52 years; ranging
      between 36 and 66 years) with medial compartment osteoarthrosis were treated with
      proximal tibia medial open-wedge osteotomy. For fixation, plates which were
      designed by the first author and which support the osteotomy surface with wedge
      shaped projections were used. The plates were either rectangular in shape with
      two or four holes or had an inverse "L" shape with four holes, and had bearing
      metal wedges of varying heights from 5 to 15 mm. Tricortical (n=8) and bicortical
      (n=43) iliac bone autografts and allografts (n=7) were used. The average follow
      up time was 21 months (ranging between 6 and 44 months). The mean preoperative
      tibiofemoral angle was 4.6 degrees varus (0 degrees -11 degrees ) while it was
      5.6 degrees valgus (2 degrees -11 degrees ) postoperatively. The mean
      preoperative HSS score was 58 (range 51-75) and it was found 89 (range 79-96)
      postoperatively. As complications, lateral tibial plateau fracture in 5 knees
      (8.6%) and lateral cortex fracture in 15 knees (25.8%) were encountered during
      surgery. Deep vein thrombosis in two cases (3.4%) and nonfatal pulmonary embolism
      in one case (1.7%), delayed wound healing in two knees (3.4%), and delayed union
      as well as breakdown of a distal screw in one knee (1.7%) were encountered
      postoperatively. In conclusion, using wedge plates for fixation of proximal tibia
      medial opening wedge osteotomy in the treatment of medial osteoarthritis with
      unicompartmental involvement of the knee, provides adequate stabilization to
      allow early movement for functional rehabilitation and keeps the obtained
      correction level.

PMID- 16568343
TI  - Screening for polymorphisms in the PXR gene in a Dutch population.
AB  - OBJECTIVE: Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of over 50%
      of all drugs currently in use. However, CYP3A4 expression shows a large inter
      individual variation that cannot only be explained by genetic polymorphisms
      identified in this gene. The pregnane X receptor (PXR) has been identified as a
      transcriptional regulator of CYP3A4. Single nucleotide polymorphisms (SNPs) in
      the PXR gene could influence PXR activity and thereby CYP3A4 expression. This
      study was therefore aimed at determining the frequencies of known SNPs and
      detecting yet unknown SNPs in the PXR gene in a Dutch population. METHODS:
      Genomic DNA was isolated from blood samples obtained from 100 healthy volunteers
      and subjected to PCR amplification, followed by DNA sequencing. The population,
      of which the ethnicity was 93% Caucasian, consisted of 79 female individuals and
      21 males. RESULTS: A total of 24 SNPs were found in the PXR gene, eight of which
      are previously unknown. The allelic frequencies found in this population varied
      from 0.5 to 73%. Most of the previously detected SNPs were located in introns.
      One new SNP, T8555G in exon 8, causes an amino acid change of C379G and is
      located in the Ligand Binding Domain of PXR. CONCLUSION: Several SNPs were
      detected in the PXR gene, one of which is located in the ligand binding domain
      (LBD). These SNPs may influence PXR-mediated CYP3A4 induction.

PMID- 16568342
TI  - Diffuse and focal brain stem tumors in childhood: prognostic factors and surgical
      outcome. Experience in a single institution.
AB  - OBJECTIVE: Brainstem tumors (BSTs) are usually gliomas and are divided into
      diffuse BSTs (DBSTs) and focal BSTs (FBSTs). The aim of this study is to
      investigate the different outcomes of these two entities. METHODS: Thirty-one
      patients with BSTs were admitted to our institution from 1995 to 2003. Patients
      with DBSTs were treated with locoregional radiotherapy (1.8 Gy/day for 54 Gy) and
      weekly vincristine for radiosensitization (1.5 mg/sm for six total doses).
      Patients with FBSTs underwent surgical resection. Chemotherapy and/or
      radiotherapy were considered in progression. RESULTS AND CONCLUSIONS: Fourteen
      patients were diagnosed as having DBSTs. The responses to treatment were ten
      cases of partial response, three of stable disease, and one of progressive
      disease. General and/or neurological symptoms improved in more than 80% of
      patients. The median time from diagnosis to progression and to death were,
      nonetheless, 8 (range of 3-13) and 13 (range of 4-25) months, respectively, with
      a 2-year overall survival rate of 12.3% [standard error (SE) 11.2]. Seventeen
      patients were diagnosed as having FBSTs. Gross total removal was achieved in 4/17
      cases, subtotal removal in 7/17, and partial removal in 6/17. There was one
      surgery-related death. Eight out of 17 patients had adjuvant chemo- and/or
      radiotherapy after progression: 6/8 are without neurological symptoms and 2/8
      have died due to tumor progression. The 4-year overall and disease-free survival
      rates are 87.4 (SE 8.4) and 58.8% (SE 11.9), respectively, the extent of
      resection being the most important prognostic factor (p=0.012). DBSTs continue to
      carry a dismal prognosis, thus demanding new treatment modalities; FBSTs can be
      treated surgically and patients benefit from a better prognosis.

PMID- 16568345
TI  - Chordoid glioma of the third ventricle.

PMID- 16568344
TI  - National campaigns to improve antibiotic use.
AB  - High levels of antibiotic consumption are driving levels of bacterial resistance
      that threaten public health. Nonetheless, antibiotics still provide highly
      effective treatments for common diseases with important implications for human
      health. The challenge for public education is to achieve a meaningful reduction
      in unnecessary antibiotic use without adversely affecting the management of
      bacterial infections. This paper focuses on the lessons learned from national
      campaigns in countries (Belgium and France) with high antibiotic use. Evaluation
      of these national campaigns showed the importance of television advertising as a
      powerful medium to change attitudes and perhaps also behaviour with regard to
      antibiotics. Moreover, in both countries, strong evidence suggested reduced
      antibiotic prescribing. However, adverse effects associated with a reduction in
      antibiotic prescribing were not monitored. We conclude that carefully designed
      mass education campaigns could improve antibiotic use nationally and should be
      considered in countries with high antibiotic use. However, these campaigns should
      employ techniques of social marketing and use appropriate outcome measures. The
      benefits and risks of such campaigns have been less well established in countries
      where antibiotic use is already low or declining.

PMID- 16568346
TI  - Fibroblast growth factor-2 augments recombinant human bone morphogenetic protein
      2-induced osteoinductive activity.
AB  - The osteoinductive activity induced by recombinant human BMP-2 (rhBMP-2) blunts
      proportionately as the recipient ages. In order to compensate for this bluntness
      administration of fibroblast growth factor-2 (FGF-2) has been considered. The aim
      of this study was to determine whether FGF-2 administration augments
      osteoinductive activity caused by rhBMP-2 and to evaluate the effect of aging on
      bone formation induced by coadministration of rhBMP-2 and FGF-2. Sixty-four
      Wistar strain male rats of 8-week-old (prepubertal) and 16-week-old
      (postpubertal) received bone defects bilaterally in the parietal bone and the
      defects were filled by a polylactic acid polyglycolic acid copolymer/gelatin
      sponge (PGS) impregnated with rhBMP-2 plus 0 ng, 25 ng, and 250 ng FGF-2 (n=10 in
      each). At 2 weeks after grafting, the new bone volume seemed to be larger in the
      rhBMP-2+FGF-2 groups than in the rhBMP-2 alone group. At 4 weeks, the new bone
      formation was linked to the adjacent original bone. In the prepubertal rats, all
      newly formed bone was similarly calcified. In the postpubertal rats, only the
      rhBMP-2+25 ng FGF-2 group showed this higher degree of calcification. At 2 weeks,
      alkaline phosphatase (ALP) activity in the rhBMP-2+25 ng FGF-2 group was
      significantly (p<0.05) larger than that in the rhBMP-2 group in both prepubertal
      and postpubertal rats. This result shows that low-dose administration of FGF-2
      enhanced the degree of calcification and ALP activity in the rhBMP-2 grafting
      site especially in the postpubertal rats. Therefore, FGF-2 would be a candidate
      to compensate for the reduction of osteoinductive activity of rhBMP-2 with aging.

PMID- 16568347
TI  - Healing and normal fibroblasts exhibit differential proliferation, collagen
      production, alpha-SMA expression, and contraction.
AB  - This study determines the differences in proliferation, collagen production,
      alpha-smooth muscle actin (alpha-SMA) expression, and contraction between healing
      and normal fibroblasts. Transected and sham-operated rat medial collateral
      ligaments (MCL) were used to obtain healing and normal fibroblasts, respectively.
      It was found that healing fibroblasts in monolayer culture proliferated 1.4-fold
      faster at 48 h and had 1.7-fold greater protein expression of alpha-SMA than
      normal fibroblasts. In addition, it was noted that the proliferation of healing
      fibroblasts in collagen gels was not significantly different from that of normal
      fibroblasts at 24 h, but it was at 48 h. Furthermore, in collagen gels, healing
      fibroblasts produced more type I collagen than normal fibroblasts and generated
      1.6- and 1.7-fold larger contractile forces at 15 and 20 h, respectively, than
      their normal counterparts. Taken together, the results of this study show that
      healing fibroblasts possess a differential proliferation, alpha-SMA protein
      expression, and contraction than normal fibroblasts.

PMID- 16568348
TI  - Mechanical interlocking of engineered cartilage to an underlying polymeric
      substrate: towards a biohybrid tissue equivalent.
AB  - This study investigates the feasibility of engineering a biohybrid cartilage
      equivalent (BCE) with the long-term goal of restoring the mechanical integrity
      and interfacial characteristics of severely damaged cartilage. The BCE depends on
      the successful adhesion, via mechanical interlocking, of a cartilage layer to a
      nondegradable composite scaffold or prosthesis. The model scaffold, consisting of
      a nonwoven mesh bonded to a solid core, was seeded with bovine articular
      chondrocytes. High molecular weight poly(L-lactic acid), which has a slow
      degradation time, was used to model the nondegradable polymer. Biochemical and
      histological analysis demonstrate that the BCE can support the growth of a
      cartilaginous matrix for at least 6 weeks in culture. Mechanical testing of the
      BCE showed cartilage adhesion strength increased from 19.27+/-1.62 to 43.79+/
      3.88 kPa between 35 and 50 days in culture. Nonmechanically interlocked cartilage
      achieved less than 5% of this adhesion strength. For the first time, atomic force
      microscopy (AFM) was used to characterize surface topography of tissue-engineered
      cartilage. Surface roughness of constructs after 8 and 10 weeks ranged from 153
      to 171 nm, falling within the range of native cartilage (100-600 nm). This study
      demonstrates the feasibility of creating a biohybrid cartilage equivalent by
      mechanically interlocking a cartilaginous layer to an underlying polymeric
      matrix.

PMID- 16568349
TI  - The effective dispersion of nanovectors within the tumor microvasculature.
AB  - The effective longitudinal diffusion of nanovectors along non-permeable and
      permeable capillaries has been studied considering the contribution of molecular
      and convective diffusion based on the Taylor's theory of shear dispersion. The
      problem is of importance in the transport of nanovectors used for the
      intravascular delivery of drugs and contrast agents. It has been shown that for a
      given capillary size and hemodynamic conditions a critical radius acr exists for
      which the effective longitudinal diffusion along the capillary has a minimum:
      Nanovectors with a < acr diffuse mainly by Brownian diffusion whereas nanovectors
      with a < acr diffuse mainly by convection and the effective diffusion coefficient
      grows with a. In permeable conduits, the effective diffusion reduces
      significantly compared to normal non-leaky vessels and it has been derived that
      acr grows almost linearly with the hydraulic permeability Lp of blood vessels. It
      has been shown that the blood conduits with the largest effective longitudinal
      diffusivity could be preferentially targeted by the circulating vectors. Based on
      these findings, the following strategies are proposed to increase the number of
      nanovectors targeting the tumor vessels: (i) The use of nanovectors with a
      critical radius for normal vessels, (ii) the injecting of bolus of nanovectors
      with different radii, and (iii) the normalization of the tumor vasculature.
      Finally, it has been emphasized that the size of the vector should be selected
      depending on the body district where the tumoral mass is developing and on the
      type, malignancy, and state of the tumor.

PMID- 16568350
TI  - Pulmonary vascular resistance and impedance in isolated mouse lungs: effects of
      pulmonary emboli.
AB  - To study pulsatile pressure-flow rate relationships in the intact pulmonary
      vascular network of mice, we developed a protocol for measuring pulmonary
      vascular resistance and impedance in isolated, ventilated, and perfused mouse
      lungs. We used pulmonary emboli to validate the effect of vascular obstruction on
      resistance and impedance. Main pulmonary artery and left atrial pressures and
      pulmonary vascular flow rate were measured under steady and pulsatile conditions
      in the lungs of C57BL/6J mice (n = 6) before and after two infusions with 25
      microm-diameter microspheres (one million per infusion). After the first and
      second embolizations, pulmonary artery pressures increased approximately two-fold
      and three and a half-fold, respectively, compared to baseline, at a steady flow
      rate of 1 ml/min (P < 0.05). Pulmonary vascular resistance and 0 Hz impedance
      also increased after the first and second embolizations for all flow rates tested
      (P < 0.05). Frequency-dependent features of the pulmonary vascular impedance
      spectrum were suggestive of shifts in the major pulmonary vascular reflection
      sites with embolization. Our results demonstrate that pulmonary artery pressure,
      resistance, and impedance magnitude measured in this isolated lung setup changed
      in ways consistent with in vivo studies in larger animals and humans and
      demonstrate the usefulness of the isolated, ventilated, and perfused mouse lung
      for investigating steady and pulsatile pressure-flow rate relationships.

PMID- 16568351
TI  - Effects of arterial bifurcation geometry on nucleotide concentration at the
      endothelium.
AB  - A mathematical and computational analysis of nucleotide concentration for a two
      dimensional artery bifurcation has been developed. This region of the vasculature
      is known to be exposed to spatially varying wall shear stress (WSS), hence the
      variation of adenosine nucleotides is of interest. A previously derived
      similarity solution for mass transport in blood boundary layers for arbitrary
      wall shear stress function has been used. For the analytical model, the geometric
      condition has been incorporated into the system using the theory for flow past a
      wedge. As the bifurcation angle varies different characteristics are exhibited,
      such as maxima in ADP concentration and the existence of a low wall shear stress
      region around the stagnation point, for large angles. In the limiting case of two
      dimensional stagnation point flow the concentration was constant throughout the
      domain length. The computational simulations provided a more detailed
      understanding into how nucleotides vary. Similarities existed between the two
      solution methods in the vicinity of the stagnation point, but deviated as the
      fully developed condition prevailed. Additionally, the effect of pulsatile flow
      has been included, leading to considerable gradients in wall shear stress, both
      temporal and spatial. However, the resulting nucleotide concentration is
      determined by the time-averaged wall shear stress. The effects of flow-induced
      ATP release have also been included, leading to significant changes in ATP
      concentration. Under rapid release, the concentration at the surface increased
      relative to the bulk concentration.

PMID- 16568352
TI  - Interferon-gamma responses to Candida recover slowly or remain low in
      immunodeficient HIV patients responding to ART.
AB  - Extended assessments of memory T-cell responses in HIV patients who have a
      satisfactory virological response to combination antiretroviral therapy (CART)
      have been limited by availability of longitudinal samples and of antigens to
      which most individuals (including HIV-negative controls) have been exposed.
      Studies of cytomegalovirus (CMV) show that interferon-gamma (IFN-gamma) responses
      never recover completely, but this may be antigen-specific. Here we present
      responses to Candida and CMV antigens analyzed using a statistical approach that
      derives overall trends from samples collected at variable time points. Results
      were considered in relation to putative markers of T-regulatory cells. Blood
      mononuclear cells collected from seventeen HIV-1 patients (nadir <100 CD4 T
      cells/mL) 0-8 years after initiation of CART were stimulated with Candida spp
      lysate, Candida enolase protein or CMV lysate and production of IFN-gamma was
      assessed by ELISpot assay. CD4 T-cell counts increased fivefold and stabilized
      within 24 months on CART, following control of plasma viremia. IFN-gamma
      responses to Candida antigens began low and increased slowly, generating positive
      slope up to 60 months on CART (Candida enolase p=0.008; Candida lysate p=0.03;
      mixed-model Wald test). Only two patients displayed a CMV or Candida-specific IFN
      gamma response above the median for seronegative controls. Proportions of T cells
      expressing CD25 or CD57 did not correlate with IFN-gamma responses. Slow
      reconstitution of IFN-gamma responses to CMV and Candida in previously
      immunodeficient patients with restored CD4+ T-cell counts on CART suggests a
      broad and nonresolving defect in memory T-cell responses.

PMID- 16568353
TI  - Structural identifiability of physiologically based pharmacokinetic models.
AB  - When starting a project in drug kinetics it is necessary to test a priori whether
      there is sufficient information in the experimental input-output design to
      estimate unique values of internal rate constants. This is an important test if
      the pharmacokinetics of a drug are to be characterised in some way by the
      parameter values estimated from the observed plasma or blood concentration
      profile. Various modifications of the well-perfused Physiologically Based
      Pharmacokinetic model (PBPK) are considered here. More complex PBPK models can be
      considered to consist of subsystems, representing groups of tissues, which are
      connected in parallel to the central compartment. A novel method of structural
      identifiability analysis is presented here that considers these subsystems
      individually. This makes analysis of subsequently modified models much simpler.
      It is found in a number of cases that these more complex systems remain globally
      identifiable and at worst reduce to locally identifiable for the additional
      parameters. A caveat is added about having more than one eliminating peripheral
      tissue.

PMID- 16568354
TI  - Goal-directed action representation in autism.
AB  - The aim of the present study was to investigate the ability of individuals with
      autism to represent goal-directed behavioural actions. We compared the
      performance of subjects with autism (n=16), mentally retarded subjects (n=14) and
      normal healthy subjects (n=15) in a sequencing task consisted in arranging
      pictures of single events in their appropriate order so as to make coherent
      stories. Three types of actions were presented: (a) actions on objects; (b)
      actions on objects in a broader spatio-temporal context; (c) interactive actions.
      Autistic subjects were impaired in arranging sequences of actions on objects, as
      compared to both control groups. This impairment might contribute to explaining
      both executive deficits and difficulties in understanding others' behaviour in
      autism.

PMID- 16568355
TI  - Teaching reciprocal imitation skills to young children with autism using a
      naturalistic behavioral approach: effects on language, pretend play, and joint
      attention.
AB  - Children with autism exhibit significant deficits in imitation skills which
      impede the acquisition of more complex behaviors and socialization, and are thus
      an important focus of early intervention programs for children with autism. This
      study used a multiple-baseline design across five young children with autism to
      assess the benefit of a naturalistic behavioral technique for teaching object
      imitation. Participants increased their imitation skills and generalized these
      skills to novel environments. In addition, participants exhibited increases in
      other social-communicative behaviors, including language, pretend play, and joint
      attention. These results provide support for the effectiveness of a naturalistic
      behavioral intervention for teaching imitation and offer a new and potentially
      important treatment option for young children who exhibit deficits in social
      communicative behaviors.

PMID- 16568356
TI  - Brief report: "the autism epidemic". The registered prevalence of autism in a
      Swedish urban area.
AB  - The objective of this study was to establish rates of diagnosed autism spectrum
      disorders (ASDs) in a circumscribed geographical region. The total population
      born in 1977-1994, living in Goteborg Sweden in 2001, was screened for ASD in
      registers of the Child Neuropsychiatry Clinic. The minimum registered rate of
      autistic disorder was 20.5 in 10,000. Other ASDs were 32.9 in 10,000, including
      9.2 in 10,000 with Asperger syndrome. Males predominated. In the youngest group
      (7-12 years), 1.23% had a registered diagnosis of ASD. There was an increase in
      the rate of diagnosed registered ASD over time; the cause was not determined. The
      increase tended to level off in the younger age cohort, perhaps due to Asperger
      syndrome cases missed in screening.

PMID- 16568357
TI  - The effects of lag schedules and preferred materials on variable responding in
      students with autism.
AB  - Effects of a Lag 1 reinforcement schedule on appropriate and varied responding to
      the social question, "What do you like to do?" and effects of the proportion of
      preferred stimuli present during training on the amount of varied responding in
      each session were investigated with students with autism. An ABAB reversal design
      and a multielement design were used to evaluate the effects of the Lag schedule
      and proportion of preferred stimuli, respectively. Results showed that a Lag 1
      schedule was effective at increasing varied vocal responding for 2 of 3
      participants. The proportion of stimuli that were preferred did not affect the
      amount of varied responding emitted.

PMID- 16568359
TI  - Comment on "Asperger syndrome: Familial, pre- and perinatal factors" by Gillberg
      and Cederland.

PMID- 16568358
TI  - Cognitive and symptom profiles in high-functioning pervasive developmental
      disorder not otherwise specified and attention-deficit/hyperactivity disorder.
AB  - Age- and IQ-balanced 27 children with high-functioning (IQ>or=70) pervasive
      developmental disorder not otherwise specified (HPDDNOS) and 27 children with
      attention-deficit/hyperactivity disorder (ADHD) were compared on the Japanese
      version of Wechsler Intelligence Scale for Children Third Edition (WISC-III) and
      the Childhood Autism Rating Scale-Tokyo Version (CARS-TV). Compared with the ADHD
      children, the HPDDNOS children scored significantly lower on verbal
      comprehension, vocabulary, and comprehension, but significantly higher on block
      design. After controlling for the total CARS-TV score, the HPDDNOS children were
      significantly more abnormal on "relationships with people," "nonverbal
      communication," and "general impressions," but less abnormal on "near receptor
      responsiveness" and "activity level." These differences in cognitive and autistic
      symptom profiles may help professionals to distinguish clinically between both
      conditions.

PMID- 16568360
TI  - Effectiveness of metal-metal and metal-organic compound combinations against
      Plutella xylostella: implications for plant elemental defense.
AB  - Plants that contain elevated foliar metal concentrations can be categorized as
      accumulators or, if the accumulation is extreme, hyperaccumulators. The defense
      hypothesis suggests that these plants may be defended against folivore attack,
      and recent research has indicated that metal concentrations at or below the
      accumulator range may be defensively effective. This experiment explored the
      toxicity of four metals hyper-accumulated by plants (Cd, Ni, Pb, and Zn) and
      asked if combinations of metals, or metals and organic chemicals, might broaden
      the defensive effectiveness of metals. Metals were used alone and in certain
      metal + metal (Zn plus Ni, Pb, or Cd) and metal + organic defensive chemical (Ni
      plus tannic acid, atropine, or nicotine) combinations. Artificial diet amended
      with these treatments was fed to larvae of the crucifer specialist herbivore
      Plutella xylostella. Combinations of metals and metals + organic chemicals
      significantly decreased survival and pupation rates, compared to single
      treatments, for at least some concentrations in every experiment. Effects of
      combinations were additive rather than synergistic or antagonistic. Because Zn
      enhanced the toxicity of other metals and Ni enhanced the toxicity of organic
      defensive chemicals, our findings suggest that the defensive effects of metals
      are more widespread among plants than previously believed. They also support the
      hypothesis that herbivore defense may have led to the evolution of metal hyper
      accumulation by increasing the preexisting defensive effects of metals at
      accumulator levels in plants.

PMID- 16568362
TI  - Enteric drainage pancreatic transplantation.
AB  - Enteric drainage is currently the preferred method of pancreatic transplantation.
      This technique results in long-term good control of diabetes. In this report we
      discuss the postoperative radiologic anatomy and complications.

PMID- 16568363
TI  - Bladder tumors: virtual MR cystoscopy.
AB  - Virtual cystoscopy is a promising new technique based on computer-simulated
      rendering of the inner surface of the urinary bladder using volumetric magnetic
      resonance (MR) imaging data, thus enabling maneuvers that normally are not
      possible with conventional cystoscopy. Due to several distinct advantages over
      conventional cystoscopy such as minimal invasiveness, evaluation of the urethral
      orifice from a cranial point of view and an opportunity to observe diverticula
      formations and the inner urethral space, gadolinium-enhanced MR cystoscopy has a
      great potential for competing with conventional cystoscopy under some clinical
      circumstances. The recent improvement in MR scanners has significantly
      facilitated virtual cystoscopic evaluation of the urinary bladder lumen by MR
      imaging. Volumetric data associated with powerful postprocessing procedures allow
      imaging of the inner urinary bladder surface with excellent detail. In this
      article, imaging techniques and clinical applications of gadolinium-enhanced
      virtual MR cystoscopy are presented.

PMID- 16568364
TI  - Looking forward.
AB  - With the rapid acceleration of technology, fundamental changes in the science of
      surgery are emerging within the lifetime of a surgeon's practice. This review
      includes the technologies of information systems, robotics, virtual reality,
      simulation and training, directed-energy surgical instruments, photonics, and
      brain chips, as well as their impact on the practice of surgery. Also considered
      are those technologies that may replace surgery, such as genetic engineering,
      tissue engineering, suspended animation, and nanotechnology. The evidence for
      each of these technologies is presented as preliminary reports of their success
      in research laboratories.

PMID- 16568365
TI  - Pesticide detoxifying functions of N-halamine fabrics.
AB  - Halamine structures incorporated on polyester/cotton fabrics were able to
      detoxify oxime carbamate pesticides that contain thio bonds rapidly upon contact.
      The reaction was endothermic, and the detoxification rate was in first order to
      concentrations of the pesticides. Aldicarb was degraded in a much faster rate
      than that of methomyl by the halamine fabrics. The reactivity of halamine
      structures was different, and imide halamine was more reactive than amine
      halamine. The detoxification was an oxidative reaction on the sulfur atom
      existing in both aldicarb and methomyl. The same halamine structures were unable
      to effectively react with carbaryl and carbofuran, which are aromatic carbamates
      and do not contain any thio bonds.

PMID- 16568367
TI  - Minimal changes in reflux esophagitis: red ones and white ones.
AB  - Minimal change esophagitis is commonly accepted as part of the spectrum of reflux
      esophagitis in Japan as well as in many reflux esophagitis classification
      systems. However, the Los Angeles system excludes minimal changes as a sign of
      reflux esophagitis because of low interobserver agreement. The high prevalence of
      minimal change esophagitis suggests that many endoscopists can recognize such
      findings in their patients' esophagi. However, we do not have a clear definition
      of minimal changes, which requires proven interobserver agreement, histological
      evidence, and response data to therapeutic intervention. Furthermore,
      erythematous changes (red ones) and acanthotic changes (white ones) are not
      distinguished in the definition of minimal change used in Japan. It is time to
      clarify such issues.

PMID- 16568366
TI  - Simultaneous measurement of noise-activated middle-ear muscle reflex and stimulus
      frequency otoacoustic emissions.
AB  - Otoacoustic emissions serve as a noninvasive probe of the medial olivocochlear
      (MOC) reflex. Stimulus frequency otoacoustic emissions (SFOAEs) elicited by a low
      level probe tone may be the optimal type of emission for studying MOC effects
      because at low levels, the probe itself does not elicit the MOC reflex [Guinan et
      al. (2003) J. Assoc. Res. Otolaryngol. 4:521]. Based on anatomical
      considerations, the MOC reflex activated by ipsilateral acoustic stimulation
      (mediated by the crossed olivocochlear bundle) is predicted to be stronger than
      the reflex to contralateral stimulation. Broadband noise is an effective
      activator of the MOC reflex; however, it is also an effective activator of the
      middle-ear muscle (MEM) reflex, which can make results difficult to interpret.
      The MEM reflex may be activated at lower levels than measured clinically, and
      most previous human studies have not explicitly included measurements to rule out
      MEM reflex contamination. The current study addressed these issues using a higher
      frequency SFOAE probe tone to test for cochlear changes mediated by the MOC
      reflex, while simultaneously monitoring the MEM reflex using a low-frequency
      probe tone. Broadband notched noise was presented ipsilaterally at various levels
      to elicit probe-tone shifts. Measurements are reported for 15 normal-hearing
      subjects. With the higher-frequency probe near 1.5 kHz, only 20% of subjects
      showed shifts consistent with an MOC reflex in the absence of an MEM-induced
      shift. With the higher-frequency probe near 3.5 kHz, up to 40% of subjects showed
      shifts in the absence of an MEM-induced shift. However, these responses had
      longer time courses than expected for MOC-induced shifts, and may have been
      dominated by other cochlear processes, rather than MOC reflex. These results
      suggest caution in the interpretation of effects observed using ipsilaterally
      presented acoustic activators intended to excite the MOC reflex.

PMID- 16568368
TI  - Management of hepatocellular carcinoma in Japan.

PMID- 16568370
TI  - Study of hemodynamic changes in portal systemic shunts and their relation to
      variceal relapse after endoscopic variceal ligation combined with ethanol
      sclerotherapy.
AB  - BACKGROUND: Among the factors influencing variceal relapse after endoscopic
      treatment, portal hemodynamic changes, especially in portal systemic shunts,
      could be the most important factor because hemodynamics are directly related to
      the development of esophageal varices. We aimed to clarify the influence of
      endoscopic treatment for esophageal varices on portal systemic shunts as well as
      its predictive value for variceal relapse. METHODS: Fifty patients who underwent
      combined endoscopic variceal ligation and injection sclerotherapy were examined
      with sonography and portography. RESULTS: Decrease of diameter, hepatopetal flow
      direction in the left gastric vein, or the presence of non-varices portal
      systemic shunt were sonographic findings related to a low incidence of variceal
      relapse. The presence of blood flow in and around the esophagus on venograms was
      highly predictive for variceal relapse. In patients with such venograms, non
      varices portal systemic shunts did not develop. CONCLUSIONS: Sonographic
      assessment of hemodynamic changes in portal systemic shunt could be useful for
      estimating the results of endoscopic treatment for esophageal varices.

PMID- 16568371
TI  - Simple and accurate (13)C-urea breath test for detection of Helicobacter pylori
      in the remnant stomach after surgery.
AB  - BACKGROUND: The efficacy of the (13)C-urea breath test (UBT) for diagnosis of
      Helicobacter pylori (H. pylori) infection in the remnant stomach after surgery is
      a matter of controversy. We report a simple and accurate method of (13)C-UBT for
      diagnosis of H. pylori infection in the remnant stomach after gastrectomy.
      METHODS: Eighty patients who had undergone gastrectomy with or without subsequent
      H. pylori eradication therapy were examined a total of 134 times for H. pylori
      infection by the (13)C-UBT. (13)C-Urea, 10mg per test, was used in powdered form
      or in the form of film-coated tablets. Breath samples were collected before and
      10, 20, and 3 min after ingestion. Mucosal biopsy specimens for bacterial culture
      and histological examination of the remnant stomach were collected endoscopically
      after each (13)C-UBT test. RESULTS: Factors that confounded the (13)C-UBT results
      in the remnant stomach were oral bacteria, posture, and residual food. Lying
      horizontally on the left side was the best position, and film-coated tablets
      indicated no necessity for use of mouthwash. The method of anastomosis had no
      significant effect on the results of the (13)C-UBT. Thirty minutes and a cutoff
      of 4.5 per thousand were optimal conditions for detection of H. pylori in the
      remnant stomach. Under these conditions, sensitivity, specificity, and accuracy
      were 79.4% (27/34 cases), 95.7% (44/46 cases), and 88.8% (71/80 cases),
      respectively, in ordinary H. pylori diagnosis, and 100% (2/2 cases), 93.3% (14/15
      cases), and 94.1% (16/17 cases), respectively, in evaluating eradication at 4
      weeks after treatment of H. pylori. CONCLUSIONS: Having the patient lie
      horizontally on the left side, using a film-coated (13)C-urea tablet without
      using mouthwash, and measurement at 3 min provided a simple and accurate method
      of (13)C-urea breath test for detection of H. pylori in the remnant stomach after
      gastrectomy.

PMID- 16568369
TI  - Update of research and management of hepatitis B.

PMID- 16568372
TI  - The significance of aberrant CHFR methylation for clinical response to
      microtubule inhibitors in gastric cancer.
AB  - BACKGROUND: We studied the correlations between CHFR (checkpoint with FHA and
      RING finger) gene methylation and responses to microtubule inhibitors (MI) in
      gastric cancer. METHODS: We examined 9 gastric cancer cell lines and 46 gastric
      cancer specimens from patients who underwent surgical resection. Promoter
      methylation was determined by methylation-specific polymerase chain reaction
      (MSP). CHFR mRNA expression was estimated by quantitative reverse transcription
      PCR. The MI-induced growth inhibition was assayed by a standard MTT method.
      RESULTS: CHFR expression was silenced by aberrant promoter methylation in 3 of 9
      gastric cancer cell lines. The level of CHFR mRNA expression was closely
      correlated with IC(50) in the MI-treated cells (R=0.889, P=0.005). In 46 patients
      with gastric cancers, 24 (52%) presented aberrant CHFR methylation. Among them,
      12 patients had received treatment with MI because of advanced-stage tumor or
      tumor recurrence after surgery. The responders to the MI treatment were 29% in
      patients with CHFR methylation and 20% in those without the methylation. However,
      6 (86%) of 7 patients with methylated CHFR tumor showed some regression or no
      progression, whereas 4 (80%) of 5 patients with unmethylated CHFR tumor
      manifested progressive deterioration. CONCLUSIONS: These observations indicated
      that CHFR methylation may be a clinically useful approach to predict the
      responsiveness of gastric cancers to treatment with MI.

PMID- 16568373
TI  - Influence of chemotherapeutic agents and cytokines on the expression of 5
      fluorouracil-associated enzymes in human colon cancer cell lines.
AB  - BACKGROUND: Several studies have demonstrated that intratumoral expression of
      catabolizing and anabolizing enzymes for 5-fluorouracil (5-FU) is important in
      the response of cancers to 5-FU-based chemotherapy. We investigated the influence
      of other chemotherapeutic agents or cytokines, which are often administered for
      enhancing the efficacy of 5-FU, on the tumoral expression of 5-FU-associated
      enzymes, i.e., dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS),
      orotate phosphoribosyl transferase (OPRT), and thymidine phosphorylase (TP).
      METHODS: Human colon cancer cell lines (HT-29, Caco-2, and DLD-1) were incubated
      with 5-FU and with 5-FU combined with cisplatin, camptothecin, paclitaxel,
      mitomycin C, interferon, or TNF-related apoptosis-inducing ligand. mRNA
      expression of 5-FU-associated enzymes was assessed by real-time PCR. Activity of
      each enzyme and intracellular 5-FU accumulation after incubation with such agents
      were also evaluated. RESULTS: Each agent had a synergistic effect on the
      cytotoxicity of 5-FU. All chemotherapeutic agents other than cytokines induced
      marked alteration of the mRNA expression profile of 5-FU-associated enzymes;
      depression of DPD, elevation of TS, and slight suppression of OPRT and TP. In
      accordance with mRNA expression, enzyme activity of DPD was significantly
      depressed by such agents. Furthermore, although 5-FU itself increased DPD mRNA
      expression, a mechanism considered to be related to the acquisition of 5-FU
      resistance, the addition of cisplatin or camptothecin significantly inhibited the
      5-FU-induced elevation of DPD. CONCLUSIONS: 5-FU-associated enzymes in colon
      cancer cells were greatly influenced by various chemotherapeutic agents; in
      particular, DPD expression was depressed. These results appear important in
      planning chemotherapy and also in understanding the development of adverse
      effects of 5-FU.

PMID- 16568374
TI  - Early reduction of infected hepatocytes by activated immunity at the time of
      interferon withdrawal hepatitis followed by lamivudine administration resulted in
      higher seroconversion in hepatitis Be antigen-positive patients with chronic
      hepatitis B.
AB  - BACKGROUND: It has been found that the efficacy of lamivudine (LAM) therapy can
      be improved by preceding administration with a short course of corticosteroid
      that induces a flare of the disease upon its withdrawal. Because of the side
      effects of corticosteroid, we tested the effect of a short course of interferon
      (IFN) as the primer instead of prednisolone, which was followed by LAM when the
      hepatitis flare occurred. The incidence of LAM resistance mutations and the
      effect of core promoter and precore mutations on the durability of the responses
      were also studied. METHODS: Patients treated with interferon (IFN)-LAM therapy
      (n=73) were compared to those treated with IFN alone (n=117). The IFN-LAM group
      received IFN-alpha MU/day, t.i.w. for a 3-month period. LAM (10mg/day during 1
      year) was started when IFN withdrawal hepatitis occurred during 2-10 months after
      stopping IFN. The LAM-resistant, core promoter, and precore mutations were
      examined by sequencing. RESULTS: (1) The IFN-LAM group developed exacerbated
      hepatitis following IFN withdrawal in 63 patients before starting LAM therapy.
      The seroconversion (SC) rate was significantly higher in the IFN-LAM group than
      in the IFN-alone group (61% vs 26%, P=0.0001). (2) The LAM resistance mutation
      rate was 31% at 1 year after initiating LAM therapy. (3) In a stepwise
      discriminant-function analysis, decreased level of HBeAg determined at 4 weeks
      after LAM administration and increased level of HBeAb before the start of LAM
      administration contributed significantly on seroconversion to anti-HBe (P =
      0.0073 and 0.004, respectively). (4) The reappearance rate of HBeAg within 6
      months after the therapy (relapse) was 33% in the IFN-LAM group and 10% in the
      IFN-alone group. The prevalence of core promoter and precore mutations did not
      change before and after the therapy, nor did these mutations correlate with the
      relapse after stopping IFN-LAM therapy. CONCLUSIONS: (1) Our findings suggest
      that early reduction of infected hepatocytes expressed by HBeAg by LAM may
      contribute to a high SC rate of IFN-LAM therapy. (2) The emergence of LAM
      resistant mutations was similar to the previously reported rate, and neither core
      promoter nor precore mutations correlated with relapse of seroconverters after
      IFN-LAM withdrawal.

PMID- 16568375
TI  - Significant elevation of serum interleukin-18 levels in patients with acute
      pancreatitis.
AB  - BACKGROUND: We have reported that peripheral lymphocyte reduction due to
      apoptosis is linked to the development of subsequent infectious complications in
      patients with severe acute pancreatitis and that Th1 (helper T cell type 1)/Th2
      (helper T cell type 2) balance tends to cause Th1 suppression in experimental
      severe acute pancreatitis. It has been reported that interleukin (IL)-18 is a
      cytokine produced from Kupffer cells and activated macrophages, and that IL-18
      acts on Th1 cells and in combination with IL-12 strongly induces production of
      interferon-gamma. However, the role of IL-18 in acute pancreatitis has not yet
      been fully understood. METHODS: Serum IL-18 concentrations were determined by an
      enzyme-linked immunosorbent assay in 43 patients with acute pancreatitis at the
      time of admission. The relationships with etiology, pancreatic necrosis,
      severity, blood biochemical parameters on admission, infection, and organ
      dysfunction during the clinical course and prognosis were analyzed. RESULTS:
      Serum IL-18 levels in patients with acute pancreatitis (656+/- 11pg/ml) were
      significantly higher than those in healthy volunteers (126+/- pg/ml). Serum IL-18
      levels were significantly positively correlated with the Ranson score and
      Japanese severity score. Among the blood biochemical parameters on admission,
      base excess and total protein were significantly negatively correlated with serum
      IL-18 levels. Moreover, the CD4/CD8 rate of lymphocytes, serum IL-6 levels, and
      serum IL-8 levels were significantly positively correlated with serum IL-18
      levels. On day 7 after admission, the CD4/CD8 rate of lymphocytes and the rate of
      CD4-positive lymphocytes were significantly positively correlated with serum IL
      18 levels. Furthermore, serum IL-18 levels in patients with hepatic dysfunction
      (980+/- 25pg/ml) were significantly higher than those without hepatic dysfunction
      (464+/- 8pg/ml). Serum IL-18 levels were not related to infection or prognosis.
      Elevation of serum IL-18 levels continued during 4 weeks after admission.
      CONCLUSIONS: These results suggest that serum IL-18 levels are significantly
      elevated and are correlated with severity in patients with acute pancreatitis and
      that IL-18 may be closely related to helper T cell response and hepatic
      dysfunction in this disease.

PMID- 16568377
TI  - A case of sumatriptan-induced intestinal ischemia.

PMID- 16568376
TI  - Gefitinib and the modulation of the signaling pathways downstream of epidermal
      growth factor receptor in human liver cancer cells.
AB  - BACKGROUND: The transforming growth factor-alpha (TGF-alpha)/epidermal growth
      factor receptor (EGFR) signaling pathway has been demonstrated to have a pivotal
      role in hepatocarcinogenesis. We examined whether abrogation of the TGF
      alpha/EGFR signaling pathway with a selective EGFR tyrosine kinase inhibitor,
      gefitinib, could inhibit the proliferation of human hepatocellular carcinoma
      (HCC) cells. METHODS: Cellular growth was monitored by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Cell-cycle distribution was
      analyzed by flow cytometric analysis. Activities of signaling molecules were
      evaluated by Western blot analysis. RESULTS: HCC cells expressed EGFR at variable
      levels; however, extracellular signal-regulated kinase (ERK)1/2 and AKT, key
      signaling molecules downstream of EGFR, were not constitutively active in the
      cells. When HCC cells were treated with TGF-alpha, cellular growth was
      accelerated in a manner dependent on activation of ERK1/2 and AKT. When the cells
      were co-treated with gefitinib and TGF-alpha, enhanced proliferation and
      activation of ERK1/2 and AKT were canceled, and the cell-cycle promotion by TGF
      alpha was inhibited by co-treatment with gefitinib and TGF-alpha, independently
      of expression levels of EGFR. In contrast, gefitinib did not show an
      antiproliferative effect on HCC cells cultivated under the 10% serum condition.
      CONCLUSIONS: The present data demonstrated that gefitinib exerted an
      antiproliferative action on HCC cells under a limited condition when signaling
      pathways downstream of EGFR were activated by TGF-alpha.

PMID- 16568378
TI  - Solid serous adenoma of the pancreas: a solid variant of serous cystadenoma or a
      separate disease entity?

PMID- 16568379
TI  - Epigenetics modulates the effect of chemotherapy on gastric cancer.

PMID- 16568380
TI  - Significance of elevated serum IL-18 levels in patients with acute pancreatitis.

PMID- 16568381
TI  - Professor Yoshinori Tashiro's contribution to orthopedic surgery.

PMID- 16568382
TI  - Internal plate fixation of fractures: short history and recent developments.
AB  - Metal plates for internal fixation of fractures have been used for more than 100
      years. Although initial shortcomings such as corrosion and insufficient strength
      have been overcome, more recent designs have not solved all problems. Further
      research is needed to develop a plate that accelerates fracture healing while not
      interfering with bone physiology. The introduction of rigid plates had by far the
      greatest impact on plate fixation of fractures. However, it led to cortical
      porosis, delayed bridging, and refractures after plate removal. These unwarranted
      effects were said to be caused by bone-plate contact interfering with cortical
      perfusion. Consequently, further plate modifications aimed to reduce this contact
      area to minimize necrosis and subsequent porosis. The advocates of limited
      contact plates have not published measurements of the contact area or proof of
      the temporary nature of the porosis. Moreover, clinical studies of newer plate
      types have failed to show a superior outcome. Histomor-phometric measurements of
      the cortex showed no difference in the extent of necrosis under plates having
      different contact areas. Necrosis was predominant in the periosteal cortical
      half, whereas porosis occurred mostly in the endosteal cortical half. No positive
      correlation was found between either. The scientific evidence to date strongly
      suggests that bone loss is caused by stress shielding and not interference with
      cortical perfusion secondary to bone-plate contact. Consequently, an axially
      compressible plate (ACP) incorporating polylactide (PLA) inserts press-fit around
      screw holes was designed. The bioresorbable inserts should allow for (1)
      increased micromotion in the axial plane to promote healing during the union
      phase and (2) gradual degradation over time to decrease stress shielding during
      the remodeling phase. Results of ongoing experimental results are encouraging.
      Only plates allowing dynamic compression in the axial plane can lead to a
      revolution in fracture fixation.

PMID- 16568383
TI  - Report on the Japanese Orthopaedic Association's 3-year project observing hip
      fractures at fixed-point hospitals.
AB  - BACKGROUND: The aim of this study was to assess the disability and mortality of
      hip fractures 1 year after initial visit (postoperatively) at fixed-point
      hospitals selected by the Japanese Orthopaedic Association Committee on
      Osteoporosis. METHOD: A total of 158 core orthopedic hospitals were selected for
      participation in this research. Subjects were all aged 65 years and older with
      hip fractures at the selected hospitals between January 1, 1999 and December 31,
      2001. A prognostic survey of activities of daily living (ADL), assessed by the
      long-term care insurance criteria established by the Ministry of Health, Labour,
      and Welfare of Japan was performed 1 year after the initial visit. RESULTS: A
      total of 1992 hip fractures in patients aged 65 to 111 years were treated over
      the 3 years from 1999 to 2001. Among the 1992 patients, 4537 had femoral neck
      fractures and 6217 had trochanteric fractures. Surgical treatment was chosen for
      85.6% of the femoral neck fractures and 88.2% of the trochanteric fractures. The
      mean duration from fracture to admission was 3.1 days, and the mean duration from
      admission to surgery was 11.2 days. The mean duration from surgery to discharge
      over the 3-year period was 49.8 days. Before hip fracture, the ratio of patients
      with J1 ("able to go out freely utilizing public transportation") or J2 ("able to
      visit immediate neighbors independently") on the long-term care insurance
      criteria was 50.9%. At 1 year after the initial visit, that result represented a
      decrease of 24.1 percentage points before hip fracture. A total of 70 patients
      died before undergoing surgery. In the present study, the 1-year mortality rate
      for the entire patient population over the 3-year period was 10.1%. CONCLUSIONS:
      Hip fracture patients show a decrease in the ADL score 1 year after the initial
      visit. Compared to other countries, the duration of hospitalization is longer in
      Japan, but the mortality rate is lower.

PMID- 16568384
TI  - Changes in total alkaline phosphatase level after hip fracture: comparison
      between femoral neck and trochanter fractures.
AB  - BACKGROUND: Biochemical bone metabolic markers are affected by fractures, and
      total alkaline phosphatase (ALP) is considered one of the bone formation markers.
      Only a few reports have dealt with changes in bone formation markers during the
      healing process of bone fragility hip fractures. Despite the difference in the
      amount of callus formation and bone fusion rate, no significant differences in
      longitudinal change of total ALP between femoral neck and trochanter fracture
      have been reported. METHODS: A total of 69 osteoporotic patients with femoral
      neck or trochanter fracture whose serum concentrations of total ALP were examined
      at least four times at six periodic examination points (1, 2, 3, 4, 6, and 8
      weeks after surgery) and whose state of bone union was obtained within 24 weeks
      after surgery were selected for this retrospective study. The characteristic
      longitudinal change of total ALP during the healing process was shown, and the
      possibility of total ALP as a predictive factor for the state of osteosynthesis
      of hip fractures is discussed. RESULTS: Changes in the total ALP level according
      to the healing process were similar for femoral neck and trochanter fractures.
      The concentration of total ALP rose to a maximum at 3 weeks after surgery and
      then gradually decreased for both fractures. However, the range of change was
      significantly greater for trochanter fractures than for femoral neck fractures.
      For trochanter fractures, total ALP decreased from 3 to 6 weeks after surgery in
      all but one patient. CONCLUSIONS: Increases in the concentration of total ALP
      after surgery and the subsequent decreases may reflect the normal healing
      process. A significant difference in the changes of total ALP after surgery
      between femoral trochanter and neck fractures was shown. Periodic measurement of
      total ALP might be useful for obtaining information on the osteosynthesis state.

PMID- 16568385
TI  - Usefulness of arterial blood gas analysis and D-dimer measurement in the
      assessment of pulmonary embolism after orthopedic surgery.
AB  - BACKGROUND: Deep venous thrombosis (DVT) and pulmonary embolism (PE) after spinal
      or lower extremity surgery are well recognized as common complications. Since
      1995 we have investigated the incidence of PE after orthopedic surgery using
      ventilation-perfusion (V/Q) lung scans, and the prevalence of PE was about 10%.
      With a view to detecting early-stage PE by simple examinations, we evaluated the
      use of both the blood gas analysis and the D-dimer measurement after spinal or
      lower extremity surgery. METHODS: Altogether, 85 patients who underwent spinal or
      lower extremity surgery were eligible for the study. Pneumatic sequential leg
      compression devices (PSLCDs) were utilized continuously both intra- and
      postoperatively. Arterial blood gas analysis and D-dimer measurement were
      performed pre- and postoperatively on days 3 and 7. We set lung scan criteria as
      follows: postoperative decrease in Pa(O2) (deltaPa(O2) by > or = 10 torr (group
      G), postoperative D-dimer of > or = 1 microg/ml (group D), or both. Patients with
      the criteria went on to undergo lung scans, and PE was diagnosed by the existence
      of any mismatch between ventilation-perfusion (V/Q) lung scans. RESULTS: A total
      of 44 (51.8%) patients met the lung scan criteria and underwent perfusion lung
      scans, 10 (11.7%) of whom were diagnosed as PE. In groups G and D, about 30%
      showed PE. Moreover, six (85.7%) of the seven patients with both criteria showed
      a significant increase (83.7%) in the prevalence of PE. CONCLUSIONS: Patients
      with the above criteria showed a high prevalence of PE. Moreover, 10 (11.7%) of
      the 85 patients were diagnosed as having PE, which corresponded to the prevalence
      in our former studies where lung scans were performed in all patients. The blood
      gas analysis and the D-dimer measurement may be utilized as the first screening
      examinations.

PMID- 16568386
TI  - Diagnosis of deep vein thrombosis after operation for fracture of the proximal
      femur: comparative study of ultrasonography and venography.
AB  - BACKGROUND: We compared investigative methods to study the diagnostic capability
      of ultrasonography. Subjects were 75 patients with proximal femur fractures who
      underwent surgery from March 2002 to December 2003. METHODS: Biochemical assays
      were carried out on days 3 and 7, and D-dimer levels were investigated as a time
      series. Ascending lower limb venography and ultrasonography were carried out
      nearly simultaneously in all cases on day 7. RESULTS: The incidence of deep vein
      thrombosis (DVT)-positive findings on venography was 61.3% (46/75). Venography
      results demonstrated a diagnostic sensitivity of 95.5% and specificity of 91.4%
      using a D-dimer cutoff of 1microg/ml on postoperative day 7. By ultrasonography,
      diagnostic sensitivity for DVT was 78.3%, and specificity was 96.5%. Among all
      proximal area cases, there were 18 limbs with DVT seen on venography among which
      were 17 limbs in cases demonstrating DVT at the same site on ultrasonography, a
      correct diagnosis rate of 94.4%. CONCLUSIONS: For the diagnosis of a thrombus
      more proximal than the popliteal area, a location at high risk for occurrence of
      pulmonary embolism, ultrasonography provided results nearly on par with those
      obtained by venography. Thus, we believe that ultrasonography allowed a more
      noninvasive, accurate diagnosis and more rapid treatment in cases where D-dimer
      values were 1 microg/ml or more on postoperative day 7.

PMID- 16568387
TI  - MRI study of bioabsorbable poly-L-lactic acid devices used for fixation of
      fracture and osteotomies.
AB  - BACKGROUND: The overall clinical results of bioabsorbable fixation devices made
      of poly-L-lactic acid (PLLA) used for fixation of fractures, bone grafting, and
      osteotomies have been favorable. However, clinical studies demonstrated no sign
      of normal bony architecture restored after surgery, although implant channels had
      been filled with fibrous tissue. The purpose of the present retrospective study
      was to examine the extent of structural changes in PLLA devices (PLLA-Ds) for
      fixation of rotational acetabular osteotomies and displaced malleolar ankle
      fractures using magnetic resonance imaging (MRI). METHODS: Altogether, 14
      patients with osteoarthritis of hip joints and 15 with displaced malleolar ankle
      fractures were operated on using PLLA-D (NEOFIX). Of these patients, 22 were
      finally enrolled in the study, and the period from operation to the time of the
      study ranged from 17 to 78 months. The postoperative radiographic findings were
      evaluated for union, and changes around the implant holes were classified as
      sclerosis, resorption, or no change. MRI was carried out to estimate changes in
      the PLLA-Ds. RESULTS: Bone union was obtained in all cases; clinical
      complications such as infection, joint effusion, soft tissue irritation due to
      PLLA-D deviation, and motion pain in the joints were not observed. The MRI study
      suggested that water content in PLLA-D increased mainly due to biodegradation and
      that implants were not replaced by bony tissue. CONCLUSIONS: The PLLA-Ds were
      degraded but were not replaced by bony tissue during the observation period.
      Considering these findings and the assumption that in bony tissues mechanical
      strength of PLLA-D decreases with time, attention should be paid to mechanical
      insufficiency, which may occur when the cross-sectional area of a PLLA-D extends
      beyond the cross-sectional area of the osteosynthesis site.

PMID- 16568388
TI  - Endoscopic anterior cruciate ligament reconstruction using a computer-assisted
      fluoroscopic navigation system.
AB  - BACKGROUND: During anterior cruciate ligament (ACL) reconstruction, placement of
      the reconstructed ligament affects the clinical results. To accomplish accurate
      and reproducible placement of the tibial bone tunnel, we employed a fluoroscopic
      navigation system for endoscopic ACL reconstruction. In this study, preciseness
      of the tibial tunnel placement was evaluated, and the advantages and
      disadvantages of this navigation system for endoscopic ACL reconstruction are
      discussed. METHODS: Altogether, 16 knees of 16 patients who had undergone ACL
      reconstruction using this system (navi group) were evaluated regarding the
      positioning of the tibial tunnel against Blumensaat's line using X-p and the
      route of the graft by magnetic resonance imaging (MRI). Another 16 knees of 16
      patients who underwent endoscopic ACL reconstruction without the navigation
      system were the controls (control group). RESULTS: At the 1-year follow-up,
      maximally extended lateral knee X-p revealed that the anterior edge of the tibial
      tunnel and Blumensaat's line were almost aligned and that roof impingement was
      avoided; the T2-weighted MR images showed that the graft was placed close to and
      parallel to the intercondylar roof in all the knees of the navi group. The ratio
      of the distance between Blumensaat's line and the anterior edge of the tibial
      tunnel at the level of the tibial plateau to the anteroposterior width in fully
      extended true lateral radiographs was 2.7% +/- 3.4% in the navi group and 8.4% +/
      7.4% in the control group. CONCLUSIONS: The computer-assisted fluoroscopic
      navigation system improves accuracy and decreases dispersion of the tibial tunnel
      placement against Blumensaat's line in single-bundle ACL reconstruction. This
      innovative device renders the reconstruction procedure more reliable, eliminating
      the problem of skeletal variation among patients. However, the function of this
      navigation system for femoral tunnel placement is insufficient at present.
      Further refinement of the system is necessary, and the method of application
      requires improvement.

PMID- 16568389
TI  - Clinical use of a newly developed calcium phosphate cement (XSB-671D).
AB  - BACKGROUND: Several kinds of thermally processed hydroxyapatite have been
      commonly used for bone defects due to bone diseases or fractures instead of
      autologous bone grafts. However, these materials do not change in form during
      surgery and are not absorbed over a long period. To overcome this disadvantage,
      calcium phosphate bone cements (CPCs) have been developed and are already in use
      in clinical cases. These materials have merit in that to be formed in situ they
      are injectable and absorbable, but there are still problems with their handling
      and their hardening properties. A newly developed CPC called XSB-671D hardens
      earlier and is more resistant to body fluids than other CPCs. The purpose of this
      article is to verify the effectiveness, safety and usefulness of this CPC (XSB
      671D) as a bone defect filler. METHODS: We conducted clinical trials at five
      medical institutions based on a unified protocol in a total of 75 cases (30
      males, 45 females). We observed the postoperative constitutional symptoms and
      local symptoms of the filling sites. The effectiveness of this material was
      evaluated by radiographs of the filled sites, and blood and urine were examined
      to evaluate any adverse effects. RESULTS: The ratio of the cases determined to be
      "effective" or "better" among the 74 cases we found qualified was 97.3%, and XSB
      671D was confirmed to be a highly effective material with beneficial effects of
      biocompatibility and osteoconduction as a bone defect filler. Additionally, there
      were no adverse effects caused by XSB-671D except one local skin reaction, which
      disappeared 2 weeks later; its safety was also thus verified. CONCLUSIONS: We
      conclude that effective, safe treatment is possible using XSB-671D in cases
      requiring filling of a bone defect as well as those with serious osteoporosis.

PMID- 16568390
TI  - Total hip arthroplasty with an uncemented hydroxyapatite-coated tapered titanium
      stem: results at a minimum of 10 years' follow-up in 104 hips.
AB  - BACKGROUND: The purpose of this study was to evaluate the minimum 10-year results
      of primary total hip arthroplasty using an uncemented, hydroxyapatite-coated
      tapered stem. Radiological signs of bone remodeling are also presented. METHODS:
      We followed a consecutive series of 105 patients (115 hips), who had had an
      uncemented, proximally hydroxyapatite-coated Bi-Metric femoral component for a
      mean of 12.2 years (range 10.0-14.9 years). The average age at operation was 52
      years. Detailed clinical and radiological analyses were performed after a minimum
      of 5 and 10 years. Eight patients (10 hips) had died, and one patient was lost to
      follow-up, leaving 104 hips for final evaluation. The clinical result was
      evaluated by the Harris Hip Score, complications, and thigh pain. RESULTS: All
      patients still had their femoral components in place at the final follow-up. The
      average Harris Hip Score after 10 years was 92 (range 50-100) with no
      deterioration over time. Radiologically, several signs of progressive remodeling
      were identified, but no stem showed signs of loosening. CONCLUSIONS: The
      intermediate clinical and radiological results with this stem are encouraging. In
      the hands of various surgeons, the stem has performed well in a young, high-risk
      population.

PMID- 16568391
TI  - Deviation of skin marker from bone target during movement of the scapula.
AB  - BACKGROUND: Recording movement of the scapula by non-invasive techniques is
      fraught with technical difficulty. One convenient method involves placing a
      single marker on the skin overlying the acromion. The purpose of this study was
      to compare translatory discrepancies between marker and underlying bone for seven
      markers affixed to the skin overlying different parts of the scapula. METHODS:
      The markers were small plastic spheres filled with machine oil, clearly visible
      on magnetic resonance imaging (MRI), placed over seven loci of the scapula,
      including the acromion, spine, medial border, lateral border, and inferior angle.
      Nine healthy men participated, assuming three positions in the MRI apparatus: (1)
      arm at the side of the trunk (starting position); (2) arm in full elevation over
      the head; and (3) hand placed behind the back at the thoracolumbar area. Visible
      markers and three loci of the scapula itself were digitized on each MRI scan,
      enabling calculation of changes in location of each marker relative to the
      scapula between the starting position and either of the other two positions.
      RESULTS: Among the seven loci examined, the marker placed atop the acromion
      deviated least from its target, 39 +/- 1 mm (mean +/- standard deviation) for
      full elevation and 15 +/- 1 mm for moving the hand behind the back. Markers along
      the medial border and at the inferior angle exhibited relatively large
      deviations, on the order of 8 mm for full elevation and 3 mm for moving the hand
      behind the back. CONCLUSIONS: For the two movements studied, involving full range
      of motion in the shoulder complex, translation of the scapula is most accurately
      recorded if the marker is placed over the acromion, but the systematic error is
      too large for such tracking to be deemed precise.

PMID- 16568392
TI  - Response of rabbit skeletal muscle to tibial lengthening.
AB  - BACKGROUND: Experimental and clinical studies have provided knowledge regarding
      osteogenesis during limb lengthening. However, response of skeletal muscle to
      limb lengthening is not fully understood, especially as concerns histogenesis. We
      studied the morphological response of rabbit skeletal muscle to limb lengthening.
      In this study, we investigated proliferation of satellite cells, responsible for
      generation of new myonuclei, during limb lengthening. METHODS: Tibialis anterior
      muscles of young and adult rabbits were subjected to lengthening at a rate of 0.5
      mm twice per day for 20 days. After lengthening, muscle wet weight was measured
      to assess skeletal muscle growth, then proliferating cell nuclear antigen was
      measured. Immunostaining was performed to analyze proliferating cells in the
      proximal, middle, and distal portions of the muscle belly and the
      musculotendinous junction. RESULTS: Muscle wet weight increased significantly
      after lengthening both in adult (0.4 g) and young (0.1 g) rabbits. Satellite
      cells showed proliferation in response to lengthening. In adult rabbits,
      satellite cell proliferation increased along the entire lengthened muscle to a
      similar degree (from 7.1% in the middle portion to 8.6% in the musculotendinous
      junction). In young rabbits, proliferation was greater in the musculotendinous
      junction (4.8%) than that in other muscle portions (2.3% in the middle and distal
      portions, and 2.4% in the proximal portion). In adult rabbits, the rate of
      increase in satellite cell proliferation was 1780% in the middle portion to 2860%
      in the musculotendinous junction, whereas the rate was between 210% in the middle
      portion and 290% in the distal portion in young rabbit. The rate of increase in
      cell proliferation by lengthening was higher in adult muscle than that in young
      muscles as well as satellite cell proliferation. CONCLUSION: These findings
      indicate that limb lengthening promotes muscle growth in both young and adult
      rabbits.

PMID- 16568394
TI  - Treatment of Kienbock's disease with cultured stem cell-seeded hybrid tendon roll
      interposition arthroplasty: experimental study.
AB  - BACKGROUND: Several procedures that consist of excision arthroplasty, intercarpal
      arthrodesis with or without excision of the lunate, proximal row carpectomy, and
      joint leveling procedures are used to treat advanced Kienbock's disease. However,
      no reconstructive surgery for a collapsed lunate has been established. The aim of
      this study was to develop a method of tendon roll interposition arthroplasty
      using a tissue-engineering technique to improve the clinical results of the
      tendon roll interposition arthroplasty for treating advanced Kienbock's disease.
      METHODS: Twenty-four Japanese white rabbits were used for this study as three
      treatment models of Kienbock's disease. The lunate of the right paw was excised,
      and then one of three kinds of tendon roll was interposed into the excision space
      as follows: group A (controls), a conventional tendon roll made of autologous
      Achilles tendon; group B (cored tendon roll) a tendon roll with a core of the
      collagen-ceramic composite; and group C (hybrid tendon roll), a scaffold seeded
      with cultured cells was rolled in the Achilles tendon. In all groups the right
      wrist was immobilized with cast 6 weeks after surgery. Wrist radiography was
      evaluated 0, 4, 6, and 12 weeks after surgery; specimens were sectioned and
      evaluated histologically 12 weeks after surgery. RESULTS: In group C the small
      shadow of the hydroxyapatite granule gradually increased until 12 weeks after
      surgery, whereas in group B the shadow of the core gradually decreased. The
      deficit spaces of the lunate remained radiographically lucent for 12 weeks after
      surgery in group A. Histological findings revealed new bone formation at the
      center and stained cartilage matrix at the peripheral of the hybrid tendon roll
      group (group C) but not in group A or B. CONCLUSIONS: Radiological and
      histological examinations proved that it is possible to make new hybrid tendon
      rolls using this method, as osteogenesis in the center and cartilage matrix in
      the peripheral of the tendon roll were revealed.

PMID- 16568393
TI  - Histological changes in intervertebral discs after smoking and cessation:
      experimental study using a rat passive smoking model.
AB  - BACKGROUND: Passive smoking has been reported to induce intervertebral disc
      degeneration in rats, and the objective of the present study was to
      histologically investigate changes in smoking-induced intervertebral disc
      degeneration after cessation of smoking. METHODS: Four-week-old rats were
      subjected to passive smoking for 8 weeks in a smoking box [20 cigarettes a day:
      one cigarette an hour (inhaled over 3 minutes and followed by ventilation with
      room air for 5 minutes)] to induce intervertebral disc degeneration. Smoke-free
      periods of different lengths were then established, and intervertebral discs were
      histologically analyzed. RESULTS: Immediately after 8 weeks of passive smoking,
      intervertebral discs exhibited cracks, tears, and misalignment of the annulus
      fibrosus, and increased fibrous tissue was seen in the nucleus pulposus. In
      addition, the level of interleukin-1beta in intervertebral discs was higher in
      the smoking group than in the non-smoking group. After cessation, progression of
      degeneration ceased, and the matrix of the nucleus pulposus and annulus fibrosus
      exhibited increased fibrous connective tissue and proteoglycan. However, there
      were no changes in annulus fibrosus misalignment. Interleukin-1beta levels also
      remained significantly elevated after 8 weeks of cessation. CONCLUSIONS: While
      the annulus fibrosus degeneration caused by smoking was partially irreversible
      after cessation of smoking, the amount of mucin (proteoglycan) in the nucleus
      pulposus and annulus fibrosus tended to increase after cessation, thus suggesting
      the possibility that smoking-induced intervertebral disc degeneration can be
      repaired to some degree by cessation of smoking.

PMID- 16568395
TI  - Effect of low protein concentration lubricants in hip simulators.
AB  - BACKGROUND: Proteins play an important role as boundary lubricants in vivo and in
      vitro. Hip simulator studies have tested various protein concentrations of
      lubricants. Several groups reported that nonphysiological pits were created with
      low protein concentrations. Our study showed details of wear findings with low
      protein concentrations. This may be the first mapping of the run-in wear
      morphology on ultra high molecular weight polyethylene (UHMWPE) cups. METHODS:
      The UHMWPE cups used were holding cobalt chrome (CoCr) balls. This study was run
      on orbital-type hip simulators at up to 1.0 million cycles (Mc). The lubricant
      was bovine calf serum (0, 3, 5, 7, 10, and 1 mg/ml protein concentrations). Two
      volumes of lubricant were used (40 and 16 ml). Volumetric wear rates were
      calculated and the cup surfaces were observed using reflected light microscopy
      (RLM) and scanning electron microscopy (SEM). RESULTS: The 40-ml volume showed a
      lower wear rate than the 160-ml volume. The RLM findings showed that the machine
      marks gradually disappeared up to 1.Mc, but there were no obvious pits on the
      polyethylene surface. The SEM findings showed nonphysiological wear phenomena in
      the 0-mg/ml protein concentration and physiological wear phenomena in the low
      protein concentrations. In the main bearing wear area, many nodules were observed
      with fibrils. In the peripheral bearing wear area, mainly ripples were observed.
      At the nonbearing wear area, folds were observed. CONCLUSIONS: Our study showed
      the microwear findings with low-protein serum: First, folds were formed, followed
      by ripples, and finally nodules accompanied by fibrils. During the run-in wear
      phase, nodules and fibrils had already appeared in the main bearing wear area.
      Thus, we need to investigate more details of the wear process when folds or
      ripples change to nodules at the main wear area in the run-in wear.

PMID- 16568396
TI  - Reconstruction using bone lengthening of the residual digit after amputation for
      the treatment of digital malignant tumors.

PMID- 16568397
TI  - Fatal pulmonary fat embolism after posterior spinal fusion surgery.

PMID- 16568398
TI  - Extensor tendon rupture in ring and little fingers with DRUJ osteoarthritis
      without perforating the DRUJ capsule.

PMID- 16568399
TI  - Three cases with periosteal osteosarcoma arising from the femur.

PMID- 16568400
TI  - Reconstruction of congenital pseudarthrosis of the clavicle in an adult.

PMID- 16568401
TI  - Collagen-hydroxyapatite composites for hard tissue repair.
AB  - Bone is the most implanted tissue after blood. The major solid components of
      human bone are collagen (a natural polymer, also found in skin and tendons) and a
      substituted hydroxyapatite (a natural ceramic, also found in teeth). Although
      these two components when used separately provide a relatively successful mean of
      augmenting bone growth, the composite of the two natural materials exceeds this
      success. This paper provides a review of the most common routes to the
      fabrication of collagen (Col) and hydroxyapatite (HA) composites for bone
      analogues. The regeneration of diseased or fractured bones is the challenge faced
      by current technologies in tissue engineering. Hydroxyapatite and collagen
      composites (Col-HA) have the potential in mimicking and replacing skeletal bones.
      Both in vivo and in vitro studies show the importance of collagen type,
      mineralisation conditions, porosity, manufacturing conditions and crosslinking.
      The results outlined on mechanical properties, cell culturing and de-novo bone
      growth of these devices relate to the efficiency of these to be used as future
      bone implants. Solid free form fabrication where a mould can be built up layer by
      layer, providing shape and internal vascularisation may provide an improved
      method of creating composite structures.

PMID- 16568403
TI  - Protein labeling with red squarylium dyes for analysis by capillary
      electrophoresis with laser-induced fluorescence detection.
AB  - Two new red luminescent asymmetric squarylium dyes (designated "Red-1c and Red
      3") have been shown to exhibit absorbance shifts to longer wavelengths upon the
      addition of protein, along with a concomitant increase in fluorescence emission.
      Specifically, the absorbance maxima for Red-1c and Red-3 dyes are 607 and 622 nm,
      respectively, in the absence of HSA, and 642 and 640 nm in the presence of HSA,
      making the excitation of their protein complexes feasible with inexpensive and
      robust diode lasers. Fluorescence emission maxima, in the presence of HSA, are
      656 and 644 nm for Red-1c and Red-3, respectively. Because of the inherently low
      fluorescence of the dyes in their free state, Red-1c and Red-3 were used as on
      column labels (that is, with the dye incorporated into the separation buffer),
      thus eliminating the need for sample derivatization prior to injection and
      separation. A comparison of precolumn and on-column labeling of proteins with
      these squarylium dyes revealed higher efficiencies and greater sensitivities for
      on-column labeling, which, when conducted with a basic, high-salt content buffer,
      permitted baseline resolution of a mixture of five model proteins. LOD for model
      proteins, such as transferrin, alpha-lactalbumin, BSA, and beta-lactoglobulin A
      and B, labeled with these dyes and analyzed by CE with LIF detection (CE-LIF)
      were found to be dependent upon dye concentration and solution pH, and are as low
      as 5 nM for BSA. Satisfactory linear relationships between peak height (or peak
      area) and protein concentration were obtained by CE-LIF for this on-column
      labeling method with Red-3 and Red-1c.

PMID- 16568404
TI  - Bacteria capture, concentration and detection by alternating current
      dielectrophoresis and self-assembly of dispersed single-wall carbon nanotubes.
AB  - The high polarizability and dielectrophoretic mobility of single-walled carbon
      nanotubes (SWNT) are utilized to capture and detect low numbers of bacteria and
      submicron particles in milliliter-sized samples. Concentrated SWNT solutions are
      mixed with the sample and a high-frequency (>100 kHz) alternating current (AC)
      field is applied by a microelectrode array to enhance bulk absorption of the
      particles (bacteria and nanoparticle substitutes) by the SWNTs via dipole-dipole
      interaction. The same AC field then drives the SWNT-bacteria aggregates to the
      microelectrode array by positive-AC dielectrophoresis (DEP), with enhanced and
      reversed bacteria DEP mobility due to the attached SWNTs. Since the field
      frequency exceeds the inverse RC time of the electrode double layer, the AC field
      penetrates deeply into the bulk and across the electrode gap. Consequently, the
      SWNTs and absorbed bacteria assemble rapidly (<5 min) into conducting linear
      aggregates between the electrodes. Measured AC impedance spectra by the same
      trapping electrodes and fields show a detection threshold of 10(4) bacteria/mL
      with this pathogen trapping and concentration technique.

PMID- 16568407
TI  - Identification of differentially expressed, tumor-associated proteins in oral
      squamous cell carcinoma by proteomic analysis.
AB  - Oral squamous cellular carcinoma is a malignant tumor with poor prognosis and
      therefore the discovery of early markers to discriminate malignant from normal
      cells would be of critical importance in clinical diagnosis. Subcellular
      fractions from oral squamous cell carcinoma (OSCC) and control samples, enriched
      in mitochondrial and cytosolic proteins, were analyzed by 2-DE, followed by MALDI
      TOF-MS. Twenty proteins showed altered expression levels in OSCC; 14 were up- and
      6 were down-regulated in comparison with the control samples. For 11 proteins,
      cofilin, C-reactive protein precursor, creatine kinase m-chain, fatty acid
      binding protein, keratin type II, myosin light chain 2 and 3, nucleoside
      diphosphate kinase A, phosphoglycerate mutase 1, plakoglobulin, and retinoic acid
      binding protein II, it is shown for the first time that they are differentially
      expressed in OSCC. Proteins with highly up-regulated levels may be of interest as
      potential diagnostic markers and consequently of clinical interest.

PMID- 16568409
TI  - Effects of weight training on quality of life in recent breast cancer survivors:
      the Weight Training for Breast Cancer Survivors (WTBS) study.
AB  - BACKGROUND: Aerobic exercise training has been shown to have beneficial effects
      on quality of life (QOL) in breast cancer survivors. However, the effects of
      weight training on psychological benefits are unknown. We sought to examine the
      effects of weight training on changes in QOL and depressive symptoms in recent
      breast cancer survivors. METHODS: A convenience sample of 86 survivors (4-36
      months posttreatment) was randomized into treatment and control groups. The
      primary outcomes were changes in QOL (CARES short form) and depressive symptoms
      (CES-D) between baseline and month 6 in this randomized controlled trial.
      RESULTS: Over 6 months the physical global QOL score improved in the treatment
      group compared with the control group (Standardized Difference = 0.62, P = .006).
      The psychosocial global score also improved significantly in the treatment group
      compared with the control group (Standardized Difference = 0.52, P = .02). There
      were no changes in CES-D scores. Increases in upper body strength were correlated
      with improvements in physical global score (r = 0.32; P <.01) and psychosocial
      global score (r = 0.30; P <.01). Increases in lean mass were also correlated with
      improvements in physical global score (r = 0.23; P <.05) and psychosocial global
      score (r = 0.24; P <.05). CONCLUSION: Twice-weekly weight training for recent
      breast cancer survivors may result in improved QOL, in part via changes in body
      composition and strength.

PMID- 16568408
TI  - Accumulation and trapping of hepatitis A virus particles by electrohydrodynamic
      flow and dielectrophoresis.
AB  - Hepatitis A virus particles (d = 27 nm) were successfully accumulated and trapped
      in a microfluidic system by means of a combination of electrohydrodynamic flow
      and dielectrophoretic forces. Electric fields were generated in a field cage
      consisting of eight microelectrodes. In addition, high medium conductance (0.3
      S/m) resulted in sufficient Joule heating and the corresponding spatial variation
      of temperature, density, and permittivity to induce electrohydrodynamic flow in
      the vicinity of the field cage. Flow vortices transport particles toward the
      center of the field cage, where dielectrophoretic forces cause permanent
      entrapment and particle aggregation. Spatial distribution of temperature,
      density, and permittivity as well as resulting flow patterns were modeled
      numerically and are in good agreement with experimental results. This
      accumulation scheme might be applicable to sample concentration enhancement in
      biosensor applications.

PMID- 16568410
TI  - Do temperamentally shy children process emotion differently than nonshy children?
      Behavioral, psychophysiological, and gender differences in reticent preschoolers.
AB  - We examined regional brain electrical activity (EEG), heart rate, and subjective
      responses at rest and during the presentation of videoclips designed to elicit a
      range of emotions (e.g., sadness, anger, happiness, fear) among a sample of
      healthy 4-year-old children selected for temperamental shyness. We found that shy
      children exhibited significantly greater relative right central EEG activation at
      rest and during the presentation of the fear-eliciting videoclip than nonshy
      children. Shy females displayed greater relative right mid-frontal EEG activation
      during the sad, happy, and fear videoclips than shy males who displayed greater
      relative left mid-frontal EEG activation. These results (1) suggest that recent
      frontal EEG activation/emotion models might be gender-specific and (2) appear to
      provide the first empirical evidence for recent theoretical notions linking the
      origins and maintenance of temperamental shyness in children to difficulty in
      regulating fear responses.

PMID- 16568411
TI  - Nonnutritive sucking: one of the major determinants of filial love.
AB  - The present study investigated the rewarding effects of nonnutritive sucking on
      the development of a filial preference. Two experiments were conducted to test
      whether nonnutritive visceral and oral stimuli have reinforcing properties
      independent from each other or act in synergy. Lambs could interact freely with
      their dam but were deprived of suckling by covering the udder for the first 12
      hr. In Experiment 1, suckling was prevented and replaced by human giving, in the
      presence of the mother, either a bottle of water (B5 and B2.5: 5% or 2.5% birth
      weight, BW, divided into seven portions over 12 hr) or water via tube-feeding (I5
      and I2.5: 5% or 2.5% BW, also divided into seven portions over 12 hr). During a
      two-choice test performed at 12 hr after birth, only B5 and I5 lambs preferred
      their mother to an alien ewe however, B5 were faster at choosing their mother at
      the beginning of the test. B2.5 and I2.5 lambs made a random choice. In
      Experiment 2, suckling was prevented and replaced by human giving, in the
      presence of the mother, either a bottle of water (B2.5: 2.5% BW, divided into
      seven portions over 12 hr) or water via tube-feeding (I10 and I2.5: 10% or 2.5%
      BW, also divided into seven portions over 12 hr). During a two-choice test at 12
      hr, tube-fed lambs (I10 and I2.5) preferred their mother to a human. B2.5 lambs
      were equally attracted to both partners and spent more time near the human than
      lambs from the other groups. In a test of reactivity to a human performed on
      neonates isolated from their mother, B2.5 lambs explored the human much more than
      the other lambs. The presence of the human had soothing properties in B2.5 lambs
      and once the human left, they were the only lambs displaying enhanced vocal and
      locomotor activity. In these experiments, nonnutritive gastrointestinal stimuli
      induced a preference for the mother whereas nonnutritive sucking led to a strong
      positive relationship with the human. These results suggest that when lambs
      suckle their dam, the development of filial bonding is facilitated through the
      combined effects of oral and gastrointestinal stimuli.

PMID- 16568412
TI  - Prenatal exposure to temporal and spatial stimulus properties affects postnatal
      responsiveness to spatial contiguity in bobwhite quail chicks.
AB  - Little is known about how experiential factors guide and organize the development
      of intersensory perception. This study manipulated the amount of late prenatal
      and early postnatal experience with the temporal synchrony and spatial contiguity
      of audio-visual stimulation available to bobwhite quail embryos and hatchlings to
      explore this question. Results revealed that only embryos exposed to temporally
      synchronous and spatially contiguous audio-visual stimulation prior to hatching
      subsequently preferred spatially contiguous audio-visual maternal information
      following hatching, despite being denied postnatal visual experience. In
      contrast, embryos that did not receive exposure to both temporal synchrony and
      spatial contiguity (and were also denied postnatal visual experience) failed to
      show a preference for the spatial contiguity of maternal auditory and visual
      information following hatching. These results suggest that prenatal exposure to
      the amodal properties of temporal synchrony and spatial contiguity facilitate
      chicks' emerging sensitivity to the spatial contiguity of audio-visual
      information in the period following hatching.

PMID- 16568413
TI  - Left versus right nipple preference in free-ranging infant rhesus macaques
      (Macaca mulatta).
AB  - The examination of nonhuman primate (NHP) lateralized behaviors may provide
      insight into the evolution of hemispheric specialization. This study examined
      nipple preference in 64 infant macaques in order to consider the ontogeny of
      lateralized behavior. We used a focal animal sampling method to record nipple
      contact during 15, 30-min observation sessions collected across each infant's
      first year of life. Using a lateralized behavior index (LBI) we calculated
      individual and population preferences (LBI=(R-L)/(R+L); "R"=mean right nipple
      contact, "L"=mean left nipple contact). Strength of preference was calculated as
      the absolute value of this score. Infants exhibited no population preference for
      a particular nipple, but showed a significant strength of preference that
      developed after 48 hr. Interestingly, successive siblings preferred the nipple
      not used by the previous infant. These findings suggest that nipple preference is
      guided by external stimuli, and that nipple preference during infancy may not be
      a behavioral representation of hemispheric specialization.

PMID- 16568414
TI  - The ontogeny of autonomic measures in 6- and 12-month-old infants.
AB  - The purpose of this study was to develop a standardized protocol to measure
      preejection period (PEP), a measure of sympathetic nervous system, and
      respiratory sinus arrhythmia (RSA), a measure of parasympathetic nervous system,
      during resting and challenging states for 6- and 12-month-old infants and to
      determine developmental changes and individual stability of these measures. A 7
      min reactivity protocol was administered to Latino infants at 6 months (n=194)
      and 12 months (n=181). Results showed: (1) it is feasible to measure PEP and RSA
      in infants, (2) the protocol elicited significant autonomic changes, (3)
      individual resting autonomic measures were moderately stable from 6 to 12 months,
      but reactivity measures were not stable, and (4) heart rate and RSA resting and
      challenge group means changed significantly from 6 to 12 months. Findings suggest
      that although infants' autonomic responses show developmental changes,
      individuals' rank order is stable from 6 to 12 months of age.

PMID- 16568415
TI  - Maternal and littermate deprivation disrupts maternal behavior and social
      learning of food preference in adulthood: tactile stimulation, nest odor, and
      social rearing prevent these effects.
AB  - Maternal and littermate (social) separation, through artificial rearing (AR),
      disrupts the development of subsequent maternal behavior and social learning in
      rats. The addition of maternal-licking-like stimulation during AR, partially
      reverses some of these effects. However, little is know about the role of social
      stimuli from littermates and nest odors during the preweaning period, in the
      development of the adult maternal behavior and social learning. The purpose of
      this study was to examine the effects of peer- and peer-and-odor rearing on the
      development of maternal behavior and social learning in rats. Female pups were
      reared with mothers (mother reared-MR) or without mothers (AR) from postnatal day
      (PND) 3. AR rats received three different treatments: (1) AR-CONTROL group
      received minimal tactile stimulation, (2) AR-ODOR females received exposure to
      maternal nest material inside the AR-isolation-cup environment, (3) AR-SOCIAL
      group was reared in the cup with maternal nest material and a conspecific of the
      same-age and same-sex and received additional tactile stimulation. MR females
      were reared by their mothers in the nest and with conspecifics. In adulthood,
      rats were tested for maternal behavior towards their own pups and in a social
      learning task. Results confirm our previous report that AR impairs performance of
      maternal behavior and the development of a social food preference. Furthermore,
      social cues from a littermate, in combination with tactile stimulation and the
      nest odor, reversed the negative effects of complete isolation (AR-CONTROL) on
      some of the above behaviors. Exposure to the odor alone also had effects on some
      of these olfactory-mediated behaviors. These studies indicate that social
      stimulation from littermates during the preweaning period, in combination with
      odor from the nest and tactile stimulation, contributes to the development of
      affiliative behaviors.

PMID- 16568416
TI  - Neonatal behavior and infant cognitive development in rhesus macaques produced by
      assisted reproductive technologies.
AB  - Assisted reproductive technologies (ART) used in fertility clinics include in
      vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), followed
      by embryo transfer into the biological or a surrogate mother. Over 1,000,000
      liveborn offspring--an estimated 1 in 150 United States newborns--have been
      produced worldwide by ART since 1978. IVF appears to produce healthy children in
      singleton pregnancies, though concerns remain regarding preterm deliveries,
      multiple pregnancies, as well as the longer-term consequences of all ART
      procedures. Clinical studies remain difficult to interpret and subject to
      confounding variables, as developmental problems may be due to a parent's
      reproductive conditions rather than, or in addition to, an ART procedure. Also,
      because of expense and time commitments, the United States ART clinical
      population is not fully representative of society diversities. This socio
      economic skewing might compensate for negative effects, masking small, or modest
      developmental deficits. Embryo splitting (ES), an ART procedure used only with
      animals, can produce genetically identical offspring. ES involves dividing four-
      to eight-cell embryos into separate blastomeres and implanting them into empty
      zona pellucida, followed by embryo transfer. Although these ART techniques have
      produced nonhuman primate offspring, there has been no research on behavioral
      safety. Here, we report the first study of behavioral development by rhesus
      macaques infants produced through ES, ICSI, and IVF. We assessed neonatal
      reflexes, self-feeding ability, recognition memory, object concept attainment,
      simple discrimination learning and reversal, and learning set (LS) acquisition.
      Although the sample sizes are small, we found no overall ART group delayed
      development. Surprisingly, the ES and ICSI monkeys appeared to be accelerated in
      attaining age milestones involving sensory-motor behaviors and a difficult Well
      Hiding object concept task. We conclude that macaque monkeys may provide an
      excellent model for the study of early human development by offspring of parents
      with conditions requiring ART pregnancies, as well as a model for the behavioral
      study of genetic-environment interactions using identical twins produced by ES.

PMID- 16568418
TI  - Combination of free-breathing and breathhold steady-state free precession
      magnetic resonance angiography for detection of coronary artery stenoses.
AB  - PURPOSE: To analyze the incremental diagnostic value of a combination of two
      approaches (free-breathing and breathhold) vs. the sole free-breathing approach
      to coronary magnetic resonance angiography (CMRA) for detection of significant
      stenoses. MATERIALS AND METHODS: Thirty patients were consecutively included in
      this prospective trial. CMRA was performed on a 1.5-T MR scanner (Magnetom
      Sonata, Siemens) using a balanced steady-state free precession (SSFP) sequence
      during free-breathing (2.4 x 0.9 x 0.7 mm3). Breathholding acquisitions (3.0 x
      1.5 x 0.7 mm3) were only performed in cases in which the quality of free
      breathing CMRA precluded assessment. Patients with contraindications to CMRA,
      claustrophobia, or nonassessable images were not excluded from the assessment of
      diagnostic accuracy (intention-to-diagnose design). RESULTS: In 60% of all free
      breathing coronary acquisitions the image quality was adequate for diagnostic
      assessment. For the remaining 40% of the cases, breathhold acquisitions were
      obtained. The sensitivity, specificity, nonassessable rate, and accuracy in
      identifying main coronary branches with significant stenoses using the
      combination of both breathing approaches and the free-breathing approach alone
      were 65% vs. 32%, 73% vs. 53%, 24% vs. 52%, and 71% vs. 46%, respectively (P <
      0.001). CONCLUSION: In this consecutive cohort of patients, the combination of
      free-breathing and breathhold CMRA significantly improved diagnostic accuracy.
      Nevertheless, even this combination did not reach accuracies sufficient for
      routine clinical application.

PMID- 16568419
TI  - Determining hierarchical functional networks from auditory stimuli fMRI.
AB  - We determined connectivity of the human brain using functional magnetic resonance
      imaging (fMRI) while subjects experienced auditory stimuli in a 2-by-2 factorial
      design. The two factors in this study were "speaker" (same or different speaker)
      and "sentence" (same or different sentences). Connectivity studies allow us to
      ask how spatially remote brain regions are neurophysiologically related given
      these stimuli. In the context of this study, we examined how the "speaker" effect
      and "sentence" effect influenced these relationships. We applied a Bayesian
      connectivity method that determines hierarchical functional networks of
      functionally connected brain regions. Hierarchy in these functional networks is
      determined by conditional probabilities of elevated activity. For example, a
      brain region that becomes active a superset of the time of another region is
      considered ascendant to that brain region in the hierarchical network. For each
      factor level, we found a baseline functional network connecting the primary
      auditory cortex (Brodmann's Area [BA] 41) with the BA 42 and BA 22 of the
      superior temporal gyrus (STG). We also found a baseline functional network that
      includes Wernicke's Area (BA 22 posterior), STG, and BA 44 for each factor level.
      However, we additionally observed a strong ascendant connection from BA 41 to the
      posterior cingulate (BA 30) and Broca's Area and a stronger connection from
      Wernicke's Area to STG and the posterior cingulate while passively listening to
      different sentences rather than the same sentence repeatedly. Finally, our
      results revealed no significant "speaker" effect or interaction between "speaker"
      and "sentence."

PMID- 16568420
TI  - The Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire is reliable in
      stroke patients.
AB  - AIMS: To investigate the test-retest reliability of Danish Prostatic Symptom
      Score (DAN-PSS-1) questionnaire in a sample of stroke patients. METHODS: A
      prospective study design was used in which the stroke patients were invited to
      complete a postal self-administrated DAN-PSS-1 questionnaire twice. The
      questionnaire consists of 12 questions related to lower urinary tract symptoms
      (LUTS). The participants were asked to state the frequency and severity of their
      symptoms (symptom score) and its impact on their daily life (bother score).
      Seventy-one stroke patients were included and 59 (83%) answered the questionnaire
      twice. The reliability test was done in two aspects: (a) detecting the frequency
      of each symptom and its bother factor, the scores were reduced to a two-category
      scale (=0, >0) and simple kappa statistics was used; (b) detecting the severity
      of each symptom and its bother factor, the total scale (0-3) and weighted kappa
      statistics was used. RESULTS: The proportion of agreement for the frequency
      symptom scores ranged from 76% to 97% and the simple kappa coefficient ranged
      from poor (kappa = 0.00) to excellent (kappa = 0.91). The proportion of agreement
      for the corresponding bother scores ranged from 76% to 95% and the simple kappa
      coefficient ranged from good (kappa = 0.61) to excellent (kappa = 0.84). The
      weighted kappa coefficient for the severity symptom scores ranged from moderate
      (kappa(w) = 0.43) to good (kappa(w) = 0.75) and the corresponding bother scores
      ranged from moderate (kappa(w) = 0.48) to good (kappa(w) = 0.68). CONCLUSIONS:
      The DAN-PSS-1 questionnaire had acceptable test-retest reliability and may be
      suitable for measuring the frequency and severity of LUTS and its bother factor
      in stroke patients.

PMID- 16568423
TI  - Evidence that some events of mammalian embryogenesis can result from differential
      growth, making migration unnecessary.
AB  - Three events during mammalian embryogenesis were reexamined that traditionally
      have been considered to be migratory. Using reconstructions of serially sectioned
      rat and human embryos and computer imaging, this descriptive study reexamined the
      following: sclerotome formation from the somite, spinal ganglion formation from
      the neural crest, and thyroid, parathyroid, and thymus gland formations from
      pharyngeal endoderm. The aim was to determine if the positional changes of the
      developing structures could be explained by differential growth (i.e., changes in
      the size and shape of the embryo and its parts) rather than migration (i.e.,
      structures moving from one region of the embryo to another). Embryos and many of
      their internal structures, especially the neural tube, rapidly change in size and
      shape during the period when migration is described, but these phenomena were not
      considered in past studies. Surface reference points were used in past
      investigations that also move as the embryo and its internal structures enlarge.
      Computer imaging makes it feasible for the first time to keep magnifications
      identical for each series of reconstructions, rendering each one equivalent to
      one frame of a motion picture film. Using this technique together with more
      centralized, less mobile reference points, the study concludes that the
      positional changes that occur during the three events can be explained by
      differential growth. Anat Rec (Part B: New Anat) 289B:53-63, 2006. (c) 2006 Wiley
      Liss, Inc.

PMID- 16568421
TI  - Functional imaging analysis contest (FIAC) analysis according to AFNI and SUMA.
AB  - The Functional Imaging Analysis Contest (FIAC) datasets were analyzed with the
      AFNI software package. Two types of linear regression analyses were carried out:
      "fixed shape" hemodynamic response, where a preselected incomplete gamma function
      is used to model each brief activation episode, and "variable shape" analysis,
      where the temporal shape of the response model in each stimulus block class is
      allowed to vary separately in each voxel. These time series regressions were
      carried out both in the volume and on the original data projected to individual
      standardized cortical surface models. Intersubject analyses were carried out
      voxel-wise on the regression amplitudes obtained from these time series results,
      using a multi-way within-subject analysis of variance (ANOVA). Group analysis of
      the block design demonstrated a significant repetition suppression of the BOLD
      signal within blocks in the superior and middle temporal gyrus. This effect may
      represent differences in the response to the first stimulus following a period of
      silence compared to the remaining sentences in the block. Analyzing the event
      related data, Brodmann area 31 showed significant sentence effect and consecutive
      sentence repetition effect. However, no significant speaker effect was found;
      these results may be consistent with the instructions to the subjects that they
      would be tested on the sentence content. Sentence by speaker interaction effects
      were found in bilateral middle temporal gyrus, left inferior frontal, and left
      inferior temporal gyrus.

PMID- 16568422
TI  - AAA award winners.

PMID- 16568424
TI  - Method for preparing permanent brain slices and serial slice images for education
      and MRI correlation.
AB  - It is important to understand the anatomical structures of the human brain in
      horizontal planes. Serially sectioned brain slices can easily be made with a meat
      slicer. The objective of this research was to enhance the educational value of
      serial brain slices made with a meat slicer through various applications. Two
      brains were taken out of two cadavers and embedded with gelatin solution to make
      two brain blocks. The first brain block was serially sectioned at 5 mm thickness
      using a meat slicer to make 28 horizontal brain slices. Each brain slice was
      embedded with a synthetic resin mixture to make 28 permanent specimens. The
      second brain block was magnetic resonance-scanned at 1.4 mm thickness to make 130
      horizontal magnetic resonance images, then serially sectioned at the same
      thickness using the meat slicer to make 130 horizontal brain slices. Each brain
      slice was scanned into a computer to make a series of slice images. Ten
      anatomical structures in the slice images were outlined to make segmented images.
      Corresponding magnetic resonance images, slice images, and segmented images were
      stacked and volume-reconstructed to make three-dimensional images, which were
      sectioned and rotated at free angles. We show that the serial brain slices made
      with a meat slicer can be permanently preserved and used in a variety of
      educational settings. Anat Rec (Part B: New Anat) 289B:64-71, 2006. (c) 2006
      Wiley-Liss, Inc.

PMID- 16568425
TI  - Anatomical reasoning in the informatics age: Principles, ontologies, and agendas.
AB  - Reasoning about anatomy shares historical scientific roots with formal logic and
      artificial intelligence. With advances in computer-based intelligent programming,
      high-level biological structural knowledge may be exploited directly for
      biomedical research, clinical tasks, and educational applications. We consider
      the special nature of anatomical domain knowledge, emphasizing the complex
      concepts and semantics that must be represented in the development of ontologies,
      formally structured databases of biological information. We review the evolution
      of the fundamental scientific principles of logic and artificial intelligence
      needed for building machines that can make use of anatomical knowledge. We look
      at methods for compiling ontologies and compare the structural designs of the
      Foundational Model of Anatomy and Open GALEN ontologies. We further consider
      issues related to mapping developing anatomy resources with other biological
      ontologies in genomics, proteomics, and physiology. Although early results are
      promising, considerable resources and continuing effort must be committed to
      completing and extending anatomical ontologies for the ultimate success of
      computer-based anatomical reasoning. Anat Rec (Part B: New Anat) 289B:72-84,
      2006. (c) 2006 Wiley-Liss, Inc.

PMID- 16568427
TI  - Elsevier to support top AAA award for anatomy education.

PMID- 16568426
TI  - Inference for magnitudes and delays of responses in the FIAC data using
      BRAINSTAT/FMRISTAT.
AB  - We used straightforward linear mixed effects models as described in Worsley et
      al. together with recent advances in smoothing to control the degrees of freedom,
      and random field theory based on discrete local maxima. This has been implemented
      in BRAINSTAT, a Python version of FMRISTAT. Our main novelty is voxel-wise
      inference for both magnitude and delay (latency) of the hemodynamic response. Our
      analysis appears to be more sensitive than that of Dehaene-Lambertz et al. Our
      main findings are greater magnitude (1.08% +/- 0.17%) and delay (0.153 +/- 0.035
      s) for different sentences compared to same sentences, together with a smaller
      but still significantly greater magnitude for different speaker compared to same
      speaker (0.47% +/- 0.08%).

PMID- 16568428
TI  - Intramyocellular lipid quantification from 1H long echo time spectra at 1.5 and 3
      T by means of the LCModel technique.
AB  - PURPOSE: To introduce a method of independent determination of CH2 and CH3
      components of intramyocellular lipids (IMCLs) by using long TE for spectra
      measurement and LCModel for spectra evaluation, to test this technique in
      controls and insulin-resistant subjects, and to compare results at 1.5 and 3 T.
      MATERIALS AND METHODS: Eight healthy volunteers and 11 patients with type 2
      diabetes mellitus underwent measurement using a 1.5-T MR scanner; six healthy
      volunteers were measured using a 3-T MR scanner. Spectra from the tibialis
      anterior muscle were acquired by using a point resolved spectroscopy (PRESS)
      sequence with the following parameters: TR/TE/ACQ = 2000 msec/270 msec/256.
      Spectra were processed by LCModel 6.1 software with two types of adopted basis
      set. RESULTS: Spectra with good separation of both CH2 and CH3 components of IMCL
      and extramyocellular lipids (EMCLs) were obtained and the LCModel routine was
      successfully applied. The reproducibility comparison (N= 7 at 1.5 T vs. N = 5 at
      3 T) showed that better results can be obtained at higher B0 values. The
      comparison of the healthy and insulin-resistant subjects proved that both
      IMCL_CH2/Cr and IMCL_CH3/Cr ratios significantly differ. CONCLUSION: Long TE
      spectroscopy of the human muscle with IMCL quantification using the LCModel
      technique can detect changes in IMCL levels as well as help in the study of fatty
      acyl chain composition. Using a higher field strength increased the intra
      individual reproducibility by approximately 150%.

PMID- 16568429
TI  - EPRI to estimate the in vivo intracerebral reducing ability in adolescent rats
      subjected to neonatal isolation.
AB  - PURPOSE: To estimate the in vivo intracerebral reducing ability after acute
      stress in adolescent rats subjected to early neonatal isolation (NI), by
      performing temporal electron paramagnetic resonance imaging (EPRI) of the brain.
      MATERIALS AND METHODS: An EPRI system operating at an EPR frequency of 700 MHz
      was used. The intracerebral reducing ability was estimated based on the halflife
      of the EPR signal of the blood-brain barrier (BBB)-permeable nitroxide radical.
      The NI treatment was performed for a period of one hour per day over postnatal
      days 2-9. Six-week-old rats were exposed to acute stress (immobilization for 90
      minutes) prior to the EPRI study. RESULTS: Depletion of the intracerebral
      reducing ability caused by the acute stress was observed; however, this depletion
      phenomenon did not occur in animals that were not subjected to NI. CONCLUSION:
      The results obtained in this study prove that NI induces cerebral vulnerability
      to acute stress in adolescence.

PMID- 16568430
TI  - Comparison of quantitative cartilage measurements acquired on two 3.0T MRI
      systems from different manufacturers.
AB  - PURPOSE: To investigate the comparability of two osteoarthritis (OA) surrogate
      endpoints--average cartilage thickness and cartilage volume--acquired from
      healthy volunteers on two 3.0T magnetic resonance imaging (MRI) systems from
      different manufacturers. MATERIALS AND METHODS: Ten knees of five healthy
      volunteers were scanned on a 3.0T General Electric (GE) and a 3.0T Philips
      scanner using a fast three-dimensional fat-suppressed spoiled gradient (SPGR)
      imaging sequence. The acquisition parameters were optimized beforehand and were
      kept as comparable as possible on both scanners. For quantitative analysis, the
      average cartilage thickness and volume of the load-bearing regions of the femoral
      condyles were compared. Data were analyzed using a univariate repeated-measures
      analysis of variance (ANOVA) to examine the effects of position, condyle, and
      imaging system on the measurements. RESULTS: The average cartilage thickness and
      volume of the load-bearing regions of the femoral condyles did not differ between
      the two different 3.0T MRI systems (P > 0.05). There was no significant effect of
      position or condyle on the average cartilage thickness measurements (P > 0.05;
      range = 0.41-0.93) or cartilage volume (P > 0.05; range = 0.14-0.87). CONCLUSION:
      Two OA surrogate endpoints--average cartilage thickness and cartilage volume-
      acquired on two 3.0T MRI systems from different manufacturers are comparable.

PMID- 16568433
TI  - An unsuspected MR projectile: a "wooden" chair with metal bracing.

PMID- 16568431
TI  - Gradient- and spin-echo T2-weighted imaging for SPIO-enhanced detection and
      characterization of focal liver lesions.
AB  - PURPOSE: To evaluate superparamagnetic iron oxide (SPIO)-enhanced breathhold T2
      weighted GRASE imaging in detection and characterization of focal liver lesions.
      MATERIALS AND METHODS: In 30 patients (including 20 with cirrhosis) with 39
      malignant and 25 benign lesions, gradient- and spin-echo (GRASE) images with two
      echo times (75 and 90 msec; GRASE75 and GRASE90) were obtained prior to and
      following administration of SPIO, and compared with respiratory-triggered and
      breathhold fast spin-echo (RT-FSE and BH-FSE) images. Two readers evaluated image
      quality and reviewed 240 liver segments for sensitivity and specificity. Signal
      to-noise ratio (SNR), and its reduction in liver and spleen after administration
      of SPIO, and lesion-to-liver contrast-to-noise ratio (CNR) were measured.
      RESULTS: Compared with RT-FSE and BH-FSE, GRASE reduced scan time by 77% to 82%
      and 21% to 27%, respectively. The image qualities with BH-FSE and GRASE75 were
      higher than with BH-FSE and GRASE90. BH-FSE showed higher specificity than RT-FSE
      and GRASE90, but otherwise there were no significant differences between pulse
      sequences for sensitivity or specificity. The mean SNR and CNR of the lesions
      with RT-FSE were significantly higher than with the other methods. SPIO-induced
      signal reduction of liver SNR was smallest with BH-FSE. CONCLUSION: GRASE is
      faster and more sensitive to SPIO than FSE, but its sensitivity and specificity
      were slightly inferior to those of BH-FSE. Image quality is a current limitation.

PMID- 16568435
TI  - A fast and highly automated approach to myocardial motion analysis using phase
      contrast magnetic resonance imaging.
AB  - PURPOSE: To develop a fast and highly automated method for calculating two
      dimensional myocardial motion and deformation using velocity encoded magnetic
      resonance imaging. MATERIALS AND METHODS: Two-dimensional phase contrast magnetic
      resonance imaging was used to acquire time resolved velocity maps of the
      myocardium. Cardiac motion was calculated by an iterative integration
      regularization scheme of low computational cost. Image segmentation was performed
      using active appearance models. RESULTS: Validation of motion tracking was
      performed in N = 47 subjects using saturation grid-tagging and closely followed
      "tag-lines." Image segmentation was validated vs. manual delineation. CONCLUSION:
      The speed and limited user interaction gives the method good potential for use in
      clinical practice.

PMID- 16568436
TI  - Multislice multiecho T2* cardiovascular magnetic resonance for detection of the
      heterogeneous distribution of myocardial iron overload.
AB  - PURPOSE: To assess the tissue iron concentration of the left ventricle (LV) using
      a multislice, multiecho T2* MR technique and a segmental analysis. MATERIALS AND
      METHODS: T2* multiecho MRI was performed in 53 thalassemia major patients. Three
      short-axis views of the LV were obtained and analyzed with custom-written
      software. The myocardium was automatically segmented into 12 segments. The T2*
      value on each segment as well as the global T2* value were calculated. Cine
      dynamic images were also obtained to evaluate biventricular function parameters
      by quantitative analysis. RESULTS: For the T2* global value, the coefficient of
      variation (CoV) for intra-/interobserver and interstudy reproducibility was 3.9%
      (r = 0.98), 5.5% (r = 0.98), and 4.7% (r = 0.99) respectively. Three groups were
      identified based on analysis of myocardial T2*: homogeneous (21%), heterogeneous
      (38%), and no myocardial iron overload (41%). The mean serum ferritin, liver iron
      concentration, and urinary iron excretion were significantly different among the
      groups. We did not find significant differences among groups in biventricular
      function. There was a correlation between the global T2* value and the T2* value
      in the mid-ventricular septum (r = 0.95, P < 0.0001). CONCLUSION: Multislice
      multiecho T2* MRI provides a noninvasive, fast, reproducible means of assessing
      myocardial iron distribution. The single measurement of mid-septal T2* correlated
      well with the global T2* value.

PMID- 16568437
TI  - Acquisition of apoptotic resistance in cadmium-induced malignant transformation:
      specific perturbation of JNK signal transduction pathway and associated
      metallothionein overexpression.
AB  - Prior work has shown that chronic cadmium exposed rat liver epithelial cells (CCE
      LE) become malignantly transformed after protracted low level cadmium exposure.
      Acquisition of apoptotic resistance is common in oncogenesis and the present work
      explores this possibility in CCE-LE cells. CCE-LE cells were resistant to
      apoptosis induced by etoposide or an acute high concentration of cadmium as
      assessed by flow cytometry with annexin/FITC. Three key mitogen-activated protein
      kinases (MAPKs), namely ERK1/2, JNK1/2, and p38, were phosphorylated in CCE-LE
      cells after acute cadmium exposure. However, the levels of phosphorylated JNK1/2
      were markedly decreased in CCE-LE cells compared to control. JNK kinase activity
      was also suppressed in CCE-LE cells exposed to cadmium. Epidermal growth factor
      (EGF), used as a positive control for stimulating JNK phosphorylation, was much
      less effective in CCE-LE cells than control cells. Ro318220 (Ro), a strong
      activator of JNK, increased phosphorylated JNK1/2 to levels similar to the
      cadmium-treated control cells and also enhanced apoptosis in response to cadmium
      in CCE-LE cells. Metallothionein (MT), which is thought to potentially inhibit
      apoptosis, was strongly overexpressed in CCE-LE cells. Further, in MT knockout
      (MT-/-) fibroblasts, JNK1/2 phosphorylation was markedly increased after cadmium
      exposure compared with similarly treated wild-type (MT+/+) cells. These results
      indicate cadmium-transformed cells acquired apoptotic resistance, which may be
      linked to the specific suppression of the JNK pathway and is associated with MT
      overexpression, which, in turn, may impact this signal transduction pathway. The
      acquisition of apoptotic resistance may play an important role in cadmium
      carcinogenesis by contributing to both tumor initiation and malignant
      progression.

PMID- 16568438
TI  - Breath-hold 3D steady-state free precession coronary MRA compared with
      conventional X-ray coronary angiography.
AB  - PURPOSE: To evaluate the use of breath-hold three-dimensional (3D) steady-state
      free precession (SSFP) coronary magnetic resonance angiography (MRA) in patients
      with coronary artery disease (CAD) in comparison with conventional coronary x-ray
      angiography (XRA). MATERIALS AND METHODS: Twenty-eight patients with suspected
      CAD were examined with the use of a breath-hold 3D-SSFP-MRA sequence and
      conventional XRA. To assess the accuracy of MRA, two clinicians who were blinded
      to patient information independently reviewed the MRA and XRA data, which were
      presented in a randomized order. To identify discrepancies between MRA and XRA,
      and assess features of coronary lesions on MRA, two additional clinicians
      examined MRA and XRA data that were presented side by side, divided into
      proximal, mid, and distal segments, and compared them segment by segment.
      RESULTS: The sensitivity and specificity for diagnosing significant coronary
      stenoses (> 50% diameter narrowing) were 64% and 94%, respectively. At sites of
      coronary lesions identified on XRA, bright signals and enlarged vessel profiles,
      in addition to the characteristic narrow lumen, were frequently observed on MRA.
      CONCLUSION: Breath-hold SSFP coronary MRA has good specificity but inconclusive
      sensitivity in diagnosing significant coronary stenoses, and provides important
      image features for depicting coronary lesions.

PMID- 16568439
TI  - Presence of unfavorable cytogenetic abnormalities is the strongest predictor of
      poor survival in secondary myelofibrosis.
AB  - BACKGROUND: Postpolycythemic (PV) and postthrombocythemic (ET) myeloid metaplasia
      are consensually referred to as secondary myelofibrosis (sMF). Prognostic
      variables in sMF are not as well defined as they are for de novo myelofibrosis
      with myeloid metaplasia (MMM), which is also known as agnogenic myeloid
      metaplasia (AMM). Such information is particularly crucial for management
      decisions in transplant-eligible patients. METHODS: Diagnoses of PV and ET
      required fulfillment of the World Health Organization criteria for the diagnosis
      of MMM as well as an antecedent history of either polycythemia vera or essential
      thrombocythemia that was supported by bone marrow examination. Cytogenetic
      findings were classified as being either favorable (normal or isolated 13q- or
      20q- clones) or unfavorable (presence of abnormalities other than 13q- and 20q-).
      RESULTS: The study population was comprised of 66 young patients (age <60 yrs)
      with sMF, including 37 patients with PV and 29 patients with ET. Multivariate
      analysis of parameters other than cytogenetics identified older age (P = .02),
      anemia (hemoglobin level <10 g/dL [P = .007]), and PV (P = .009) to be
      independent risk factors for shortened survival. However, when such analysis was
      restricted to patients in whom cytogenetic studies were performed (n = 31
      patients), the presence of unfavorable cytogenetic abnormalities (i.e., clones
      other than 20q- and 13q-) became the only adverse prognostic factor for survival
      (P = .001). A similar analysis in a temporal cohort of 50 age-matched patients
      with AMM also identified unfavorable cytogenetics as an independent predictor of
      poor survival, along with thrombocytopenia and anemia. CONCLUSIONS: The results
      of the current study suggest that cytogenetic findings might supersede AMM
      derived prognostic scoring systems for predicting survival in patients with sMF.

PMID- 16568440
TI  - Cyclin E expression is correlated with tumor progression and predicts a poor
      prognosis in patients with ovarian carcinoma.
AB  - BACKGROUND: Cyclins, cyclin dependent kinases (cdks), and their inhibitors act in
      combination to regulate progression through the cell cycle and often are
      dysregulated in carcinoma. The authors hypothesized that cyclin E plays an
      important role in ovarian carcinogenesis and that its overexpression may be an
      indicator of a poor prognosis. METHODS: Immunohistochemical analysis of cyclin E
      expression was performed by image analysis in normal ovaries, cystadenomas,
      tumors of low malignant potential, and 405 primary ovarian carcinomas by using
      tissue microarray technology. RESULTS: Overexpression of cyclin E was found in
      63.2% of the samples and was associated with clear cell, poorly differentiated,
      and serous carcinoma (P < or = .001), high-grade tumors (P < or = .001), late
      stage disease (P = .002), age older than 60 years at the time of diagnosis (P =
      .04), and suboptimal cytoreduction (P = .001). A high percentage of cyclin E
      expressing cells was associated with a poor outcome in univariate and in
      multivariate analyses. In addition, cyclin E levels also reduced survival in the
      late-stage disease group and in patients who underwent suboptimal debulking.
      CONCLUSIONS: Cyclin E was identified as an independent prognostic factor in
      patients with ovarian carcinoma. The accumulation of cyclin E protein may be a
      late event in tumorigenesis and may contribute to disease progression in these
      patients.

PMID- 16568441
TI  - Behavioral and educational limitations after chemotherapy for childhood acute
      lymphoblastic leukemia or Wilms tumor.
AB  - BACKGROUND: The improved prognosis of childhood cancer makes monitoring of
      functional outcome important. The purpose of this study was to evaluate
      behavioral and educational functioning in survivors of childhood acute
      lymphoblastic leukemia (ALL) or a Wilms tumor. In this study, children with ALL
      received central nervous system directed chemotherapy without cranial
      irradiation. METHODS: In a multicenter study, behavioral functioning and school
      performance was examined in 199 children age 4 to 18. Sixty-four children were at
      least 1 year from finishing treatment with chemotherapy for ALL (n = 28) or a
      Wilms tumor (n = 36). They were compared with siblings (n = 37) and with a
      control group of healthy schoolchildren (n = 98). RESULTS: A moderately increased
      risk of behavioral and educational problems was found in children with ALL but
      not in children with Wilms tumor. School performance was poorer in children with
      ALL attending primary school compared with same-age peers; however, the rate of
      utilization of special education services was low. Teacher-rated behavior and
      mathematics performance was correlated with attention function in children with
      ALL. An excess of problem behavior and underperformance at school was found in
      the ALL high-risk group compared with the standard-risk group. No differences
      were found between siblings and controls. CONCLUSION: Evidence is provided of
      subtle but significant behavioral and educational problems in survivors of
      childhood ALL, but no dysfunctions in survivors of a Wilms tumor. Careful follow
      up of children with ALL treated with chemotherapy only is warranted.

PMID- 16568442
TI  - Fiberoptic bronchoscopy and bronchoalveolar lavage for the evaluation of
      pulmonary disease in children with primary immunodeficiency and cancer.
AB  - BACKGROUND: Patients with childhood cancer or primary immunodeficiencies (PID)
      are at high risk for developing pulmonary infections and non-infectious
      complications. The broad differential diagnoses and the critical condition of
      these patients often drive physicians to start broad-spectrum antibiotic therapy
      before a definite diagnostic procedure is performed. A definite diagnosis may be
      achieved in these situations by fiberoptic bronchoscopy (FOB) and bronchoalveolar
      lavage (BAL). PATIENTS AND METHODS: The records of 58 PIDs and cancer
      (immunocompromised group) pediatric patients who underwent 62 fiberoptic
      bronchoscopies between 2000 and 2004 were retrospectively reviewed and compared
      to 158 non-cancer patients who underwent 182 fiberoptic bronchoscopies during the
      same period. RESULTS: The overall diagnostic rate achieved by macroscopic
      inspection of purulent secretions or hemorrhage, abnormal cell count, and
      infectious agent isolation in the immunocompromised patients was 84%. A definite
      organism was recovered in 53.2% of the patients. Probable infection defined as
      purulent secretions or abnormal cell count without infectious agent isolation was
      diagnosed in another 21% of the patients. The rate of complications was 30.6%. In
      the control group, the overall diagnostic rate was 76.9% (n.s) and an infectious
      agent was demonstrated in 12.1% (P < 0.001). Probable infection was diagnosed in
      24.2% (n.s) while the rate of complications was lower (15%) (P < 0.01).
      CONCLUSIONS: Rapid and accurate diagnoses were achieved in most procedures
      performed on immunocompromised patients. Although the rate of complications was
      higher in the immunocompromised group, they were usually very mild with no
      mortality. Based on these results, broncoalveolar lavage should be considered as
      an initial diagnostic tool in pediatric immunocompromised patients with pulmonary
      complications.

PMID- 16568443
TI  - Failure of intravenous pentamidine prophylaxis to prevent pneumocystis pneumonia
      in a pediatric hematopoietic stem cell transplant (HSCT) patient.

PMID- 16568444
TI  - Periodontal tissue healing following flap surgery using an Er:YAG laser in dogs.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to compare periodontal
      tissue healing following flap surgery using an Er:YAG laser with that of
      conventional surgery. STUDY DESIGN/MATERIALS AND METHODS: Bilateral premolars
      with experimentally induced periodontitis in six dogs were treated by periodontal
      flap surgery. Degranulation and root debridement in the furcation were performed
      using an Er:YAG laser or curet. At 3 months postsurgery, animals were sacrificed
      and decalcified specimens were prepared for histological and histometric
      analysis. RESULTS: Degranulation and root debridement were effectively performed
      with an Er:YAG laser without major thermal damage and significantly faster than
      with a curet. Histologically, the amount of newly formed bone was significantly
      greater in the laser group than in the curet group, although both groups showed
      similar amounts of cementum formation and connective tissue attachment.
      CONCLUSIONS: The Er:YAG laser irradiation can be safely and effectively utilized
      in periodontal flap surgery, and has the potential to promote new bone formation.

PMID- 16568445
TI  - Using evolutionary and structural information to predict DNA-binding sites on DNA
      binding proteins.
AB  - Proteins that interact with DNA are involved in a number of fundamental
      biological activities such as DNA replication, transcription, and repair. A
      reliable identification of DNA-binding sites in DNA-binding proteins is important
      for functional annotation, site-directed mutagenesis, and modeling protein-DNA
      interactions. We apply Support Vector Machine (SVM), a supervised pattern
      recognition method, to predict DNA-binding sites in DNA-binding proteins using
      the following features: amino acid sequence, profile of evolutionary conservation
      of sequence positions, and low-resolution structural information. We use a
      rigorous statistical approach to study the performance of predictors that utilize
      different combinations of features and how this performance is affected by
      structural and sequence properties of proteins. Our results indicate that an SVM
      predictor based on a properly scaled profile of evolutionary conservation in the
      form of a position specific scoring matrix (PSSM) significantly outperforms a
      PSSM-based neural network predictor. The highest accuracy is achieved by SVM
      predictor that combines the profile of evolutionary conservation with low
      resolution structural information. Our results also show that knowledge-based
      predictors of DNA-binding sites perform significantly better on proteins from
      mainly-alpha structural class and that the performance of these predictors is
      significantly correlated with certain structural and sequence properties of
      proteins. These observations suggest that it may be possible to assign a
      reliability index to the overall accuracy of the prediction of DNA-binding sites
      in any given protein using its sequence and structural properties. A web-server
      implementation of the predictors is freely available online at
      http://lcg.rit.albany.edu/dp-bind/.

PMID- 16568446
TI  - Wrong parameters can give just any results.

PMID- 16568447
TI  - Molecular dynamics study of a calmodulin-like protein with an IQ peptide:
      spontaneous refolding of the protein around the peptide.
AB  - The Calmodulin (CaM) is a small (16.7 kDa), highly acidic protein that is crucial
      to all eukaryotes by serving as a prototypical calcium sensor. In the present
      study, we investigated, through molecular dynamics simulations, the dynamics of a
      complex between the Mlc1p protein, which is a CaM-like protein, and the IQ4
      peptide. This protein-peptide interaction is of high importance because IQ motifs
      are widely distributed among different kinds of CaM-binding proteins. The Mlc1p
      IQ4 complex, which had been resolved by crystallography to 2.1 A, confers to a
      Ca(+2)-independent stable structure. During the simulations, the complex
      undergoes a complicated modulation process, which involves bending of the angles
      between the alpha-helices of the protein, breaking of the alpha-helical structure
      of the IQ4 peptide into two sections, and formation of new contact points between
      the protein and the peptide. The dynamics of the process consist of fast sub
      picosecond events and much slower ones that take a few nanoseconds to completion.
      Our study expands the information embedded in the crystal structure of the Mlc1p
      IQ4 complex by describing its dynamic behavior as it evolves from the crystal
      structure to a form stable in solution. The article shows that careful
      application of molecular dynamics simulations can be used for extending the
      structural information presented by the crystal structure, thereby revealing the
      dynamic configuration of the protein in its physiological environment.

PMID- 16568448
TI  - Inhibition of protein-protein interactions: the discovery of druglike beta
      catenin inhibitors by combining virtual and biophysical screening.
AB  - The interaction between beta-catenin and Tcf family members is crucial for the
      Wnt signal transduction pathway, which is commonly mutated in cancer. This
      interaction extends over a very large surface area (4800 A(2)), and inhibiting
      such interactions using low molecular weight inhibitors is a challenge. However,
      protein surfaces frequently contain "hot spots," small patches that are the main
      mediators of binding affinity. By making tight interactions with a hot spot, a
      small molecule can compete with a protein. The Tcf3/Tcf4-binding surface on beta
      catenin contains a well-defined hot spot around residues K435 and R469. A 17,700
      compounds subset of the Pharmacia corporate collection was docked to this hot
      spot with the QXP program; 22 of the best scoring compounds were put into a
      biophysical (NMR and ITC) screening funnel, where specific binding to beta
      catenin, competition with Tcf4 and finally binding constants were determined.
      This process led to the discovery of three druglike, low molecular weight Tcf4
      competitive compounds with the tightest binder having a K(D) of 450 nM. Our
      approach can be used in several situations (e.g., when selecting compounds from
      external collections, when no biochemical functional assay is available, or when
      no HTS is envisioned), and it may be generally applicable to the identification
      of inhibitors of protein-protein interactions.

PMID- 16568449
TI  - Comparing programs for rigid-body multiple structural superposition of proteins.
AB  - Different programs and methods were employed to superimpose protein structures,
      using members of four very different protein families as test subjects, and the
      results of these efforts were compared. Algorithms based on human identification
      of key amino acid residues on which to base the superpositions were nearly always
      more successful than programs that used automated techniques to identify key
      residues. Among those programs automatically identifying key residues, MASS could
      not superimpose all members of some families, but was very efficient with other
      families. MODELLER, MultiProt, and STAMP had varying levels of success. A genetic
      algorithm program written for this project did not improve superpositions when
      results from neighbor-joining and pseudostar algorithms were used as its starting
      cases, but it always improved superpositions obained by MODELLER and STAMP. A
      program entitled PyMSS is presented that includes three superposition algorithms
      featuring human interaction.

PMID- 16568450
TI  - Why do men choose one treatment over another?: a review of patient decision
      making for localized prostate cancer.
AB  - Treatment choices for localized prostate cancer appear to vary widely, although
      it is unclear whether this variation is a result of patient values or other
      factors. The authors conducted a systematic review of the literature, identifying
      70 articles that focused on prostate cancer decision making. Studies suggest that
      men consider several issues when making treatment decisions. The authors found
      conflicting evidence regarding the importance that men place on cancer
      eradication, with considerable variation in how patients interpret evidence
      regarding treatment efficacy. The number of physicians that men see and the
      importance of the physician recommendation were found to vary considerably.
      Although men stated that side effects are important, few patients reported that
      side effect factors ultimately influenced their treatment choice. To the authors'
      knowledge, there is little research regarding how patients' personal values shape
      and influence their decision, or the role of race/ethnicity or socioeconomic
      status in preferences for treatment. The authors conclude that variations in
      treatment decisions may be more indicative of differences in the information
      patients receive rather than truly reflective of underlying patient preferences.
      Considerable progress is needed in helping patients fully understand how to
      balance the complex issues surrounding prostate cancer treatment decision making.

PMID- 16568451
TI  - An open-label, multinational, multicenter study of G17DT vaccination combined
      with cisplatin and 5-fluorouracil in patients with untreated, advanced gastric or
      gastroesophageal cancer: the GC4 study.
AB  - BACKGROUND: Gastrin hormone is trophic to in vitro gastric cancer, and the
      antigastrin antibodies (AGAs) are antiproliferative and antimetastatic. Human
      gastric cancers overexpress gastrin genes and receptors that react to gastrin's
      trophic effects. Immunogen G17DT elicits a specific and high-affinity AGA. The
      authors evaluated G17DT vaccination given with cisplatin plus 5-fluorouracil for
      the treatment gastric adenocarcinoma. METHODS: In this multicenter, Phase II
      study, patients received G17DT vaccination intramuscularly on Weeks 1, 5, 9 and
      25 and cisplatin plus 5-fluorouracil every 28 days. Eligible patients had
      untreated, metastatic, or unresectable gastric or gastroesophageal adenocarcinoma
      with near-normal organ function. The primary endpoint of the study was the over
      response rate (ORR), and secondary endpoints included overall survival (OS),
      safety, and the impact of successful vaccination on patient outcome. RESULTS: In
      total, 103 patients were enrolled in 5 countries. Seven patients who were
      overdosed inadvertently with 5-fluorouracil (a major protocol violation) were
      removed from the analysis. The confirmed ORR was 30% in 79 patients who were
      evaluated for response. The median time-to-progression (TTP) was 5.4 months, and
      the median survival (MS) was 9.0 months (n = 96 patients). Sixty-five of 94
      patients who were vaccinated (69%) had 2 consecutive AGA titers of > or =1 units
      (successfully vaccinated patients or immune-responders). The TTP was longer in
      immune-responders than in immune-nonresponders (P = .0005). Similarly, the MS was
      longer in immune-responders than in immune-nonresponders (10.3 months vs. 3.8
      months; P < or =.0001). In a multivariate analysis, successful vaccination was an
      independent OS prognosticator (P = .0001). G17DT did not have an adverse effect
      on safety. CONCLUSIONS: The results demonstrated that successful G17DT
      vaccination was correlated with longer TTP and MS. AGA response was an
      independent OS prognosticator. A Phase III evaluation of G17DT in gastric cancer
      is warranted.

PMID- 16568452
TI  - Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer.
AB  - Somatic mutations in mitochondrial DNA (mtDNA) have been demonstrated in various
      tumors, including breast cancer. However, it still remains unclear whether the
      alterations in mtDNA are related to the clinicopathological features and/or the
      prognosis in the breast cancer. We analyzed somatic mutations in the D-loop
      region, the common 4,977-bp deletion, and the copy number of mtDNA in breast
      cancer and paired nontumorous breast tissues from 60 Taiwanese patients. We found
      that 18 of the 60 (30%) breast cancers displayed somatic mutations in mtDNA D
      loop region. The incidence of the 4,977-bp deletion in nontumorous breast tissues
      (47%) was much higher than that in breast cancers (5%). The copy number of mtDNA
      was significantly decreased in 38 of the 60 (63%) breast cancers as compared to
      their corresponding nontumorous breast tissues (P = 0.0008). The occurrence of D
      loop mutations was associated with an older onset age (>or=50 years old, P =
      0.042), and tumors that lacked expressions of estrogen receptor and progesterone
      receptor (P = 0.024). Patients with mtDNA D-loop mutation and breast cancer had
      significantly poorer disease-free survival than those without mutation, when
      assessed by Kaplan-Meier curves and log-rank test (P = 0.005). Multivariate Cox
      regression analysis indicated that a D-loop mutation is a significant marker that
      is independent of other clinical variables and that it can be used to assess the
      prognosis of patients. Our findings suggest that somatic mutations in mtDNA D
      loop can be used as a new molecular prognostic indicator in breast cancer.

PMID- 16568454
TI  - PTSD and depression after the Madrid March 11 train bombings.
AB  - The March 11, 2004, train bombings in Madrid, Spain, caused the largest loss of
      life from a single terrorist attack in modern European history. We used a cross
      sectional random digit dial survey of Madrid residents to assess the prevalence
      of posttraumatic stress disorder (PTSD) and major depression in the general
      population of Madrid 1 to 3 months after the March 11 train bombings. Of
      respondents 2.3% reported symptoms consistent with PTSD related to the March 11
      bombings and 8.0% of respondents reported symptoms consistent with major
      depression. The prevalence of PTSD was substantially lower, but the prevalence of
      depression was comparable to estimates reported after the September 11 attacks in
      Manhattan. The findings suggest that across cities, the magnitude of a terrorist
      attack may be the primary determinant of the prevalence of PTSD in the general
      population, but other factors may be responsible for determining the population
      prevalence of depression.

PMID- 16568453
TI  - A pilot study of an intervention to prevent negative mental health consequences
      of forensic mortuary work.
AB  - This preliminary study investigated an intervention to mitigate mental health
      effects of forensic mortuary work. Fourteen peer-nominated opinion leaders at two
      mortuaries were trained in traumatic stress management methods. Effect was
      examined on variables assessing stress management and effects of traumatic
      stress. Sixty-two staff members participated. At baseline, opinion leaders did
      not differ from their colleagues on any variable. After intervention, opinion
      leaders had significantly better scores in comparison to coworkers in leisure
      repertoire, problem solving, and positive states of mind, but no difference in
      use of avoidance or social support, or in interpersonal relationships.
      Qualitative data suggests that opinion leaders had increased self-awareness,
      improved ability to tolerate unchangeable stressors, and increased belief in
      their ability to make changes.

PMID- 16568455
TI  - The association between caregiver substance abuse and self-reported violence
      exposure among young urban children.
AB  - This study examined the relative importance of caregiver substance abuse as a
      correlate of child-reported exposure to violence. A total of 407 female African
      American primary caregivers and their children age 6 to 7 were evaluated. The
      association between child report of violence and exposure to substance abuse by
      others (both within and outside the home) was considered after controlling for
      variance accounted for by child characteristics, caregiver characteristics, home
      environment, and neighborhood environment (including neighborhood crime).
      Caregiver alcohol abuse, children's witnessing of drug use in the home, and
      children's witnessing of drug deals all explained significant additional variance
      in violence exposure. These findings suggest that for early elementary-age
      children, meaningful prevention of violence exposure may be possible via
      addressing their exposure to substance abuse in their home and community.

PMID- 16568456
TI  - Self-attributions of blame in sexually abused adolescents: a mediational model.
AB  - This study evaluates the mediational role of general attributions in explaining
      the impact of specific attributions regarding sexual abuse (SA) on six
      posttraumatic symptoms. One hundred three SA female adolescents (13-17 years old)
      completed the Trauma Symptoms Checklist for Children (TSCC; Briere, 1989), the
      blame/guilt subscale of the Children's Impact of Traumatic Events Scale (CITES-R;
      Wolfe, Gentile, Michienzi, Sas, & Wolfe, 1991), and the Personal Attributions for
      Negative Events subscale of the Children's Attributions and Perceptions Scale
      (CAPS; Mannarino, Cohen, & Berman, 1994). Results indicate that general
      attributions act as a mediator between specific attributions and six
      posttraumatic symptoms (i.e., anxiety, depression, sexual concerns, posttraumatic
      stress, dissociation, and anger).

PMID- 16568457
TI  - Anger and its association to distress and social/occupational functioning in
      symptomatic disaster relief workers responding to the September 11, 2001, World
      Trade Center disaster.
AB  - Empirical evidence suggests that anger plays a significant role in posttraumatic
      stress disorder (PTSD) and may impede recovery from traumatic events. The purpose
      of this study was to assess the role of anger and its relationship to distress
      and social/occupational functioning in disaster relief workers (DRWs) who had
      PTSD symptoms who were deployed to the World Trade Center after September 11,
      2001. Six hundred twenty-six utility workers (96% male) completed measures of
      anger, distress, PTSD severity, and social/occupational functioning. Results
      indicated that anger was significantly higher in DRWs who had PTSD symptoms than
      in those who did not, and statistically significant associations were found among
      anger, distress, PTSD severity, and social/occupational functioning in workers
      who had PTSD symptoms. Careful assessment of anger in DRWs exposed to traumatic
      events is warranted as well as longitudinal studies to further understand the
      relationship between anger and PTSD.

PMID- 16568458
TI  - Metastatic melanoma to lymph nodes in patients with unknown primary sites.
AB  - BACKGROUND: The natural history of metastatic melanoma in lymph nodes in the
      absence of a known primary site (MUP) has been defined poorly; thus, treatment
      guidelines for patients with MUP are not clear-cut. METHODS: The authors
      conducted a retrospective analysis of consecutive patients with melanoma (from
      1990 to 2001) who underwent surgical resection for melanoma metastatic to
      regional lymph nodes. Among those patients, 71 patients with MUP and 466 control
      patients who had regional lymph node metastases of similar stage with a known
      primary site were identified. Associations between clinicopathologic factors and
      survival were estimated by using the Cox proportional hazards model. RESULTS:
      After they underwent lymph node dissection, patients with MUP were classified
      with N1b disease (47%), N2b disease (14%), or N3 disease (39%). With a median
      follow-up of 7.7 years, the 5-year and 10-year overall survival rates were 55%
      and 44%, respectively, for patients with MUP, compared with 42% and 32%,
      respectively, for the control group (P = .04). In multivariate analyses, age 50
      years or older, male gender, and N2b or N3 disease status were identified as
      adverse prognostic factors, and MUP was identified as a favorable prognostic
      factor (hazard ratio, 0.61; 95% confidence interval, 0.42-0.86; P = .006) for
      overall survival. CONCLUSIONS: The relatively favorable long-term survival of
      patients with MUP in the current study suggested that patients with MUP have a
      natural history that is similar to (if not better than) the survival of many
      patients with Stage III disease. Therefore, patients with MUP should be treated
      with an aggressive surgical approach with curative intent and should be
      considered for Stage III adjuvant therapy protocols. Cancer 2006. (c) 2006
      American Cancer Society.

PMID- 16568459
TI  - Clinical features and correlates of gemcitabine-associated lung injury: findings
      from the RADAR project.
AB  - BACKGROUND: Gemcitabine is a commonly used chemotherapeutic agent structurally
      and pharmacologically similar to cytarabine. Recently, instances of severe
      gemcitabine-associated lung injury have been reported. Herein, investigators
      affiliated with the Research on Adverse Drug Events and Reports (RADAR)
      pharmacovigilance program evaluated clinical characteristics of gemcitabine
      associated severe acute lung injury from clinical trial reports, medical
      literature case reports, and spontaneous reports to the Food and Drug
      Administration (FDA) Adverse Event Reporting System (AERS). METHODS: Clinical
      data were obtained by reviewing adverse event case reports for gemcitabine
      associated lung injury as reported in the medical literature and in the FDA AERS
      database. Upper limit estimates of ADE rate were derived from review of published
      clinical trials reporting gemcitabine-associated lung injury rates of 10% or
      higher. RESULTS: A total of 178 reports of gencitabine-associated lung injury
      were identified; in AERS, there were 55 cases from clinical trials and 92
      spontaneous reports. A comprehensive search revealed 31 medical literature
      reports. Clinical features of gemcitabine-associated lung injury included
      dyspnea, fever, pulmonary infiltrate, and cough with recognition of toxicity
      occurring after a median duration of 48 (range, 1-529) days after initiation of
      gemcitabine. The taxanes, docetaxel and paclitaxel, were frequently reported as
      coadministered therapies. Eleven Phase II or Phase III clinical trials with 317
      patients identified gemcitabine-associated lung injury rates of greater than 10%,
      with the highest rates (22% and 42%) being observed in Phase III clinical trials
      where Hodgkin disease patients were treated with a regimen that included
      gemcitabine and bleomycin. CONCLUSIONS: High rates of gemcitabine-associated
      severe lung injury were observed when gemcitabine was combined with other
      therapies known to also cause lung injury. Physicians should have a high index of
      suspicion for this toxicity and report the relevant clinical findings to the
      FDA's AERS.

PMID- 16568460
TI  - The ISTSS/Rand guidelines on mental health training of primary healthcare
      providers for trauma-exposed populations in conflict-affected countries.
AB  - Mental health care for trauma-exposed populations in conflict-affected developing
      countries often is provided by primary healthcare providers (PHPs), including
      doctors, nurses, and lay health workers. The Task Force on International Trauma
      Training, through an initiative sponsored by the International Society for
      Traumatic Stress Studies and the RAND Corporation, has developed evidence- and
      consensus-based guidelines for the mental health training of PHPs in conflict
      affected developing countries. This article presents the Guidelines, which
      provide a conceptual framework and specific principles for improving the quality
      of mental health training for PHPs working with trauma-exposed populations.

PMID- 16568461
TI  - An evaluation of three brief programs for facilitating recovery after assault.
AB  - Ninety female recent assault survivors who met symptom criteria for posttraumatic
      stress disorder (PTSD) were randomized to one of three interventions: Brief
      Cognitive Behavioral Intervention, which focused on processing the traumatic
      event (B-CBT); assessment condition (AC); or supportive counseling (SC). Within 4
      weeks of an assault, participants met weekly with a therapist for four 2-hr
      sessions. Across all interventions, participants reported decreases in PTSD
      symptoms, depression, and anxiety over time. At postintervention, participants in
      B-CBT reported greater decreases in self-reported PTSD severity and a trend
      toward lower anxiety than those in SC. At 3-month follow-up, participants in B
      CBT evidenced lower general anxiety than those in SC and a trend toward lower
      self-reported PTSD severity. At last available follow-up (on average, 9-months
      postassault), all three interventions were generally similar in outcome. These
      findings suggest that a trauma-focused intervention aimed at those with severe
      PTSD symptoms after an assault can accelerate recovery.

PMID- 16568462
TI  - Posttraumatic stress disorder and the use of general health services in postwar
      Kosovo.
AB  - Studies conducted in high-income countries have demonstrated that posttraumatic
      stress symptoms are positively correlated with increased use of general health
      services; however, comparative data are lacking in postwar settings. This survey
      was conducted in Kosovo after the end of the conflict; 996 people, age 16 or
      older, were interviewed. Older age, lower education level, worse physical health,
      and current diagnosis of posttraumatic stress disorder (PTSD) were associated
      with higher use of any health services. After adjusting for gender, age, place of
      residence, type of education, poverty, refugee status, and subjective physical
      health, PTSD remained associated with an increased use of most health care
      services. Our results underline the importance of taking into account PTSD when
      restoring health services in postwar countries.

PMID- 16568463
TI  - Ten years after the genocide: trauma confrontation and posttraumatic stress in
      Rwandan adolescents.
AB  - A decade after the 1994 Rwandan genocide, we interviewed a total of 68 Rwandan
      orphans about their war experiences and posttraumatic stress disorder (PTSD)
      symptoms. The two samples comprised youth living either in a child-headed
      household (CHH) or in an orphanage. All had been exposed to extreme levels of
      violence and 41% had witnessed the murder of their own mother or father. Of the
      sample, 44% had PTSD. PTSD vulnerability was greater for youth who at the time of
      the study lived in CHH than those in an orphanage; it was also higher in those
      aged 8 to 13 during the outbreak of the genocide than those aged 3 to 7 at the
      time. Furthermore, a significant relationship was found between the number of
      traumatic experiences and subsequent stress responses.

PMID- 16568464
TI  - Screening for PTSD in motor vehicle accident survivors using the PSS-SR and IES.
AB  - The current study compares the total scores of two potential posttraumatic stress
      disorder (PTSD) screening tools, the Impact of Event Scale (IES) and the PTSD
      Symptom Scale, Self-Report (PSS-SR), to the Clinician-Administered PTSD Scale
      (CAPS) in a large sample of motor vehicle accident (MVA) survivors (N = 229, of
      whom 43% met criteria for PTSD). For the IES using a cutoff score of 27,
      sensitivity was .91, specificity was .72, and overall correct classification was
      .80. For the PSS-SR using a cutoff score of 14, sensitivity was .91, specificity
      was .62, and overall correct classification was .74. Compared to those in studies
      of other trauma populations, the identified IES cutoff score is somewhat lower
      for this population of MVA survivors and the identified PSS-SR cutoff score is
      consistent with previous findings. These data support the use of the IES and the
      PSS-SR as PTSD screening tools in MVA samples.

PMID- 16568466
TI  - The Acute Stress Checklist for Children (ASC-Kids): development of a child self
      report measure.
AB  - This project aimed to develop and validate a brief, practical self-report measure
      of acute stress disorder (ASD) reactions (including ASD diagnostic criteria) in
      children and adolescents. A draft measure was reviewed for content validity by an
      expert panel, piloted with youth, and revised for clarity and coverage of key
      constructs. The new 29-item Acute Stress Checklist for Children (ASC-Kids) was
      administered to 176 youth age 8 to 17 who had a recent injury or intensive care
      unit admission. The ASC-Kids demonstrated strong test-retest reliability and
      internal consistency, as well as concurrent and predictive validity with other
      traumatic stress measures. Results of exploratory factor analyses were consistent
      with current conceptualizations of acute traumatic stress reactions. The ASC-Kids
      is a promising measure of child acute stress reactions.

PMID- 16568465
TI  - Language use in imagined dialogue and narrative disclosures of trauma.
AB  - Support exists in many populations for the use of written disclosure to express
      thoughts and emotions about a traumatic experience. The present study examined
      language use in a variation of the writing task modified to include an imagined
      dialogue with another person. We hypothesized that this method would increase
      cognitive, affective, and present-tense word use, all of which are linked with
      beneficial outcomes from writing. We randomly assigned 169 college students to
      write in one of three conditions: trauma narrative, trauma dialogue, or control
      writing. Results suggested that writing about traumatic experiences in the form
      of a dialogue promotes greater present-oriented, affective experiencing and
      cognitive processing than does writing in the form of a narrative.

PMID- 16568467
TI  - Trauma narratives in posttraumatic stress disorder: a review.
AB  - Nineteen empirical studies providing evidence about the nature of trauma
      narratives in posttraumatic stress disorder (PTSD) were reviewed. Selected
      studies had participants with a diagnosis of PTSD or with PTSD symptoms. The
      studies used either linguistic indices or participants' rating of narrative
      quality. There was evidence of a relationship between PTSD specific pathology and
      the occurrence of sensory/perceptual references and disturbed temporal aspects.
      Evidence for PTSD-related narrative fragmentation was inconclusive, and there
      were little data about specific self-referential content. Poor validity and
      confusion of content and syntactic aspects of narrative organization limited the
      data on the organization of PTSD narratives. Approaches that address some of
      these limitations and allow narrative-based evaluation of memory for trauma in
      PTSD are outlined.

PMID- 16568469
TI  - Effects of three PTSD treatments on anger and guilt: exposure therapy, eye
      movement desensitization and reprocessing, and relaxation training.
AB  - This study sought to investigate the efficacy of prolonged exposure, eye movement
      desensitization and reprocessing, and relaxation training on trait anger and
      guilt and on trauma-related anger and guilt within the context of posttraumatic
      stress disorder (PTSD) treatment. Fifteen PTSD patients completed each treatment
      and were assessed at posttreatment and at 3-month follow-up. All three treatments
      were associated with significant reductions in all measures of anger and guilt,
      with gains maintained at follow-up. There were no significant treatment
      differences in efficacy or in the proportion of patients who worsened on anger or
      guilt measures over the course of treatment. Between-treatment effect sizes were
      generally very small. Results suggest that all three treatments are associated
      with reductions in anger and guilt, even for patients who initially have high
      levels of these emotions. However, these PTSD therapies may not be sufficient for
      treating anger and guilt; additional interventions may be required.

PMID- 16568470
TI  - PTSD and physical comorbidity among women receiving Medicaid: results from
      service-use data.
AB  - Patterns of physical comorbidity among women with posttraumatic stress disorder
      (PTSD) were explored using Michigan Medicaid claims data. PTSD-diagnosed women (n
      = 2,133) were compared with 14,948 randomly selected women in three health
      outcome areas: ICD-9 categories of disease, chronic conditions associated with
      sexual assault history in previous research, and reproductive health conditions.
      PTSD was associated with increased risk of all categories of diseases (OR range =
      1.3-4.8), endometriosis (OR = 2.7), and dyspareunia (OR = 3.4). When PTSD was not
      complicated by other mental health conditions, odds ratios for chronic conditions
      ranged from 1.9 for fibromyalgia to 4.3 for irritable bowel. Comorbidity with
      depression or a dissociative or borderline personality disorder raised risk in a
      dose-response pattern.

PMID- 16568471
TI  - Results from a pilot Phase I trial of gefitinib combined with docetaxel and
      estramustine in patients with hormone-refractory prostate cancer.
AB  - BACKGROUND: Gefitinib, which is an orally active epidermal growth factor receptor
      tyrosine kinase inhibitor, has demonstrated activity against hormone-refractory
      prostate cancer (HRPC) in preclinical studies. In this pilot Phase I trial, the
      authors evaluated the tolerability, efficacy, and pharmacokinetics of gefitinib
      combined with estramustine and docetaxel in patients with HRPC. METHODS: Patients
      received gefitinib (at a dose of 250 mg/day or 500 mg/day) on each day of a 21
      day treatment cycle. Docetaxel (at a dose of 60 mg/m(2)) was administered on Day
      1, and estramustine (at a dose of 280 mg) was administered 3 times daily on Days
      1 through 5. RESULTS: Fifteen patients were recruited at each gefitinib dose
      level. The most common adverse events observed were consistent with the known
      profiles of gefitinib, docetaxel, and estramustine. No dose-limiting toxicity was
      observed. Adverse events considered to be gefitinib related included diarrhea (n
      = 23 patients), rash (n = 8 patients), nausea (n = 7 patients), dry skin (n = 6
      patients), and emesis (n = 6 patients). Overall, 9 of 22 evaluable patients
      (40.9%) experienced a pain response. and 9 of 30 patients (30%) had a prostate
      specific antigen response. A partial objective tumor response was demonstrated in
      1 of 13 evaluable patients (7.7%) in each dose group; the median time to
      progression for both doses combined was 185 days (range, 28-233 days). Data
      comparisons within individual patients suggested that docetaxel and estramustine
      had no effect on gefitinib steady-state levels. Gefitinib had no effect on
      docetaxel exposure at the 250-mg dose but decreased exposure at the 500-mg dose.
      However, gefitinib may increase exposure to estramustine, particularly at the 500
      mg/day dose. CONCLUSIONS: The results of the current study demonstrated that
      gefitinib combined with estramustine and docetaxel had acceptable and predictable
      tolerability. However, it is unclear whether gefitinib provides an additional
      clinical benefit over docetaxel and estramustine alone.

PMID- 16568472
TI  - Prognostic impact of molecular markers in a series of 220 primary glioblastomas.
AB  - BACKGROUND: In contrast to oligodendrogliomas, molecular predictors of prognosis
      have not been consistently found in glioblastomas. However, genetic studies show
      that glioblastomas consist of several genetic subtypes and raise the possibility
      that molecular alterations could be predictive of survival. METHODS: A search for
      loss of heterozygosity (LOH) on chromosome 1p, 9p, 10q, 19q, EGFR (epidermal
      growth factor receptor), CDK4, and MDM2 (mouse double minute) amplifications,
      CDKN2A (INK4A/ARF) homozygous deletions, p53 expression, was performed in a
      series of 220 primary glioblastomas. The molecular alterations were then
      correlated with each other to identify distinct molecular pathways and with
      clinical parameters and the course of the disease to identify prognostic markers.
      RESULTS: Nonrandom associations were found between EGFR amplification and LOH10q,
      LOH9p, and INK4A/ARF deletion, LOH1p and LOH19q, and MDM2 and CDK4 amplification,
      whereas mutual exclusions were found between p53 expression and EGFR
      amplification, LOH 9p/INK4A/ARF homozygous deletion, and MDM2 and CDK4
      amplification. Age (P = 4.10(-5)) and performance status (P = .003) were the main
      predictors of outcome. In contrast, molecular markers were of limited impact:
      MDM2 amplification correlated with poor outcome on both univariate and
      multivariate analysis (P = .01) and EGFR amplification with good prognosis on
      multivariate analysis (P = .02). CONCLUSION: Despite their limited prognostic
      impact, the genetic markers investigated here outline distinct molecular pathways
      involved in glioblastoma tumorigenesis and warrant broader molecular screening.

PMID- 16568474
TI  - JC-1, a sensitive probe for a simultaneous detection of P-glycoprotein activity
      and apoptosis in leukemic cells.
AB  - BACKGROUND: JC-1 probe has been successfully used for the analysis of either
      apoptosis or P-glycoprotein (P-gp) activity. Therefore, we wanted to see if JC-1
      could also simultaneously assess both, P-gp activity and apoptosis, in acute
      myeloid leukemia (AML) cells. METHODS: P-gp activity was measured using JC-1 and
      compared to the results of the Rhodamine 123 (Rh 123) assay in P-gp negative and
      P-gp positive cell lines, and 12 AML samples. For apoptosis, spontaneous
      apoptosis, as well as, apoptosis induced by Cytosine Arabinosine and
      Homoharringtonine were analyzed. Both mitochondrial red fluorescence and
      cytoplasmic green fluorescence of JC-1 with and without a P-gp inhibitor
      (Cyclosporine A : CsA) were used for the identification of apoptotic cells, and
      this was compared to Annexin V/PI staining. RESULTS: (1) We found a good
      correlation between JC-1 and Rh 123 in viable cells. Even in a small population
      of viable cells, P-gp positive cells emitting low red fluorescence, gained on red
      fluorescence after P-gp inhibition with CsA permitting an evaluation of P-gp
      activity. (2) We found a good correlation between the Annexin V/PI staining and
      JC-1 (P < 0.0001) in the assessment of apoptotic cells. Most importantly, the
      apoptotic cells could be distinguished by the loss of red fluorescence and the
      increase of green fluorescence without any change after P-gp inhibition with CsA.
      CONCLUSIONS: JC-1 can simultaneously evaluate two important parameters involved
      in drug resistance in AML cells, P-gp activity and apoptosis.

PMID- 16568475
TI  - CD38 as a prognostic factor in B cell chronic lymphocytic leukaemia (B-CLL):
      comparison of three approaches to analyze its expression.
AB  - BACKGROUND: Increased CD38 expression by leukemic cells has been suggested as an
      adverse prognostic factor in B-CLL. Several approaches have been proposed to
      quantify its level of expression by flow cytometry. METHODS: We compared the use
      of (i) the percentage of CD38 positive cells, (ii) CD38 antibodies bound per cell
      (ABC), and (iii) a semi-quantitative method based on the shape of the CD38
      histogram, within a cohort of 78 B-CLL patients. RESULTS: A decreased overall
      survival was seen with >30% CD38 positivity among B-CLL cells, with CD38 ABC
      >100, and with bimodal or unimodal, strongly positive CD38 histograms. However,
      patients with unimodal weakly positive CD38 histograms also showed a
      significantly reduced survival as did patients with intermediate proportions
      (i.e. 5-30%) of CD38+ cells. Furthermore, within the group with <5% CD38
      positivity among their B-CLL cells, 84% of patients showed prognostically
      favourable mutated IGVH gene segments and 100% had low ZAP70 gene expression. For
      5-30% CD38 positivity, these proportions were 50 and 83%, while for >30% CD38
      positivity, these proportion were only 28 and 56%, respectively. CONCLUSIONS: We
      found a simple method of quantitation of CD38 expression (i.e., >5% CD38
      positivity among B-CLL cells) to be sufficient to identify patients with an
      unfavourable prognosis. The level of CD38 expression as defined with this method
      correlated well with the IGVH mutation status and ZAP70 gene expression.

PMID- 16568476
TI  - Cytometric analysis of BAL T cells labeled with a standardized antibody cocktail
      correlates with immunohistochemical staining.
AB  - BACKGROUND: Determining T-cell phenotypes of lung cells obtained by
      bronchoalveolar lavage (BAL) is frequently clinically useful, particularly for
      evaluating causes of interstitial lung disease. The current standard of
      determining CD4/CD8 T-cell subsets by immunohistochemical (IHC) staining of
      cytocentrifuge slides is labor-intensive and subject to interpreter variation.
      Flow cytometry (FCM) is a precise and rapid method commonly used in research to
      characterize cells in the lung. However, few studies address the methodology of
      analysis of BAL lymphocytes by FCM. METHODS: Patients underwent bronchoscopy for
      clinical purposes. A BAL cell differential and T-cell subtype was requested by
      the treating physician to supplement the evaluation of patients with suspected
      interstitial lung disease. We used a commercially available T-cell antibody
      reagent, approved for analysis of blood via FCM, for T-cell subtyping of clinical
      BAL specimens. RESULTS: The percentages of CD4 and CD8 T-cell populations, as
      well as the CD4/CD8 ratios showed excellent correlation with IHC staining of
      cytocentrifuge slides regardless of the acquisition program used, as long as the
      gating strategy remained consistent (r > or = 0.9693 for CD4, r > or = 0.9589 for
      CD8, and r > or = 0.9485 for the CD4/CD8 ratio). CONCLUSION: These findings
      validate the use of standardized, commercially available antibody cocktails for
      BAL lymphocyte subtyping, making this technique available to clinicians and
      researchers with access to a three-color or four-color flow cytometer.

PMID- 16568478
TI  - On the role of oxygen defects in the catalytic performance of zinc oxide.

PMID- 16568477
TI  - Temporal responses in the disruption of iron regulation by manganese.
AB  - Manganese (Mn) is an essential trace element, though at elevated exposures it is
      also a neurotoxicant. Several mechanisms underlying manganese toxicity have been
      investigated, although a consistent mechanism(s) of action at low exposures has
      not been fully elucidated. Here we systematically evaluated the effects of in
      vitro manganese exposure on intracellular iron (Fe) homeostasis and iron
      regulatory protein (IRP) binding activity in undifferentiated PC12 cells over a
      range of manganese exposure concentrations (1, 10, 50, and 200 microM MnCl(2))
      and exposure durations (12, 24, 36, and 48 hr), to test the hypothesis that
      moderately elevated manganese exposure disrupts cellular iron regulation. Results
      demonstrate that manganese exposure produces a rapid and sustained dose-dependent
      dysregulation of cellular iron metabolism, with effects occurring as early as 12
      hr exposure and at manganese doses as low as 1 microM. Manganese exposure altered
      the dynamics of IRP-1 binding and the intracellular abundance of IRP-2, and
      altered the cellular abundance of transferrin receptor, ferritin, and
      mitochondrial aconitase protein levels. Cellular levels of labile iron were
      significantly increased with manganese exposure, although total cellular iron
      levels were not. The overall pattern of effects shows that manganese produced an
      inappropriate cellular response akin to iron deficiency, to which the cells were
      able to mount a compensatory response. Consistent with our previous studies,
      these data indicate that even low to moderate exposures to Manganese in vitro
      significantly disrupt cellular iron metabolism, which may be an important
      contributory mechanism of manganese neurotoxicity.

PMID- 16568479
TI  - Hockey-Puck micelles from oligo(p-benzamide)-b-PEG rod-coil block copolymers.

PMID- 16568480
TI  - Soluble single-molecule nanogels of controlled structure as a matrix for
      efficient artificial enzymes.

PMID- 16568481
TI  - Mixed Mg/Li amides of the type R2NMgCl.LiCl as highly efficient bases for the
      regioselective generation of functionalized aryl and heteroaryl magnesium
      compounds.

PMID- 16568482
TI  - Preparation of helicenes through olefin metathesis.

PMID- 16568483
TI  - Regiospecific C-H bond activation: reversible H/D exchange promoted by CuI
      complexes with triazamacrocyclic ligands.

PMID- 16568484
TI  - Polyionic gels: efficient heterogeneous media for metal scavenging and catalysis.

PMID- 16568485
TI  - Formamide hydrolysis in alkaline aqueous solution: insight from Ab initio
      metadynamics calculations.

PMID- 16568486
TI  - Reaction of molecular oxygen with a PdII- hydride to produce a PdII
      hydroperoxide: acid catalysis and implications for Pd-catalyzed aerobic oxidation
      reactions.

PMID- 16568487
TI  - Solvent exchange in thermally stable resorcinarene nanotubes.
AB  - The assembly of C-methyl resorcinarene into a tubular supramolecular solid-state
      structure, its thermal stability, and its hosting properties are reported.
      Careful control of the crystallisation conditions of C-methyl resorcinarene and
      1,4-dimethyl-1,4-diazoniabicyclo[2.2.2]octane (1,4-dimethyl DABCO) dibromide
      leads to a formation of two crystallographically different, but structurally very
      similar, solid-state nanotube structures. These structures undergo a remarkable
      variety of supramolecular interactions, which lead to the formation of 0.5 nm
      diameter nonpolar tubes through the crystal lattice. The formation of these tubes
      is templated by suitably sized small alcohols, namely, n-propanol, 2-propanol, or
      n-butanol. The self-assembly involves close pi...pi interactions between the
      adjacent resorcinarenes, and C--H...pi and cation...pi interactions between the
      resorcinarenes and the guest 1,4-dimethyl DABCO dications. The crystals of these
      supramolecular tube structures are thermally very stable and the included solvent
      alcohol can be removed from the tubes without breaking the single-crystalline
      structure of the assembly. After removal of the solvent molecules the tubes can
      be filled with other small, less polar solvent molecules such as dichloromethane.

PMID- 16568488
TI  - Micellization and reversible pH-sensitive phase transfer of the hyperbranched
      multiarm PEI-PBLG Copolymer.
AB  - A novel, hyperbranched, amphiphilic multiarm biodegradable polyethylenimine
      poly(gamma-benzyl-L-glutamate) (PEI-PBLG) copolymer was prepared by the ring
      opening polymerization of gamma-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA)
      with hyperbranched PEI as a macroinitiator. The copolymer could self-assemble
      into core-shell micelles in aqueous solution with highly hydrophobic micelle
      cores. As the PBLG content was increased, the size of the micelles increased and
      the critical micelle concentration (CMC) decreased. The surface of the micelles
      had a positive zeta potential. The cationic micelles were capable of complexing
      with plasmid DNA (pDNA), which could be released subsequently by treatment with
      polyanions. The PEI-PBLG copolymer formed unimolecular micelles in chloroform
      solution. The pH-sensitive phase-transfer behavior exhibited two critical pH
      points for triggering the encapsulation and release of guest molecules. Both the
      encapsulation and release processes were rapid and reversible. Under strong
      acidic or alkaline conditions, the release process became partially or completely
      irreversible. Thus, this copolymer system should be an attractive candidate for a
      gene- or drug-delivery system in aqueous media and could provide the phase
      transfer carriers between water and organic media.

PMID- 16568489
TI  - Design and synthesis of novel propellanes by using claisen rearrangement and ring
      closing metathesis as the key steps.
AB  - Novel hexacyclic caged compounds are prepared by a combination of Claisen
      rearrangement and ring-closing metathesis (RCM). Additionally, a Grignard
      reaction in conjugation with RCM produced intricate hexacyclic caged molecules.

PMID- 16568490
TI  - Self-supported chiral catalysts for heterogeneous enantioselective reactions.
AB  - The development of heterogeneous chiral catalysts for enantioselective reactions
      is highly desirable in order to overcome some drawbacks of homogeneous catalysts.
      Different from the conventional approaches by using various types of supports or
      biphasic systems for the recovery and reuse of homogeneous catalysts, a
      conceptually new strategy for heterogenization of homogeneous chiral catalysts,
      that is, a "self-supporting" approach, has been developed to use homochiral metal
      organic coordination polymers generated by the self-assembly of chiral multitopic
      ligands with metal ions, and thus obviates the use of any support. In this
      concept article, the success of this "self-supporting" strategy will be
      exemplified in heterogeneous catalysis of asymmetric carbonyl-ene, sulfoxidation,
      epoxidation, and asymmetric hydrogenation reactions.

PMID- 16568491
TI  - Towards carbohydrate derivatives of the ReI(CO)3 fragment.
AB  - With the [Re(CO)(3)Br(3)](2-) ion as a precursor for the Re(I)(CO)(3) fragment,
      the diols (1R,2R)-cyclohexane-1,2-diol [(1R,2R)-Chxd], anhydroerythritol
      (AnEryt), and (1S,2S)-cyclopentane-1,2-diol [(1S,2S)-Cptd] form dinuclear
      monoanions in the salts (NBu(4))[(Re(2)(CO)(6){mu-(1R,2R)-ChxdH(-1)}(3)] (1),
      [K([18]crown-6)][Re(2)(CO)(6)(mu-OMe)(2)(mu-AnErytH(-1))] (2) and
      (NBu(4))[Re(2)(CO)(6){mu-(1S,2S)-CptdH(-1)}(3)] (3). The monoanionic diolato
      ligands in these triply bridged dirhenates(I) are monodentate. Bridging triolato
      ligation in the trirhenates(I) is supported by the anions of glycerol (Glyc) and
      methyl beta-D-ribopyranoside (Me-beta-D-Ribp), the latter binding in its (1)C(4)
      conformation, in (DBUH)(2)[Re(3)(CO)(9)(mu(3)-O)(mu(3)-GlycH(-3))]0.5 MeCN (4 a),
      (NEt(4))[Re(3)(CO)(9)(mu(3)-OMe)(mu(3)-GlycH(-3))] (4 b) and
      (DBUH)[Re(3)(CO)(9)(mu(3)-OMe)(mu(3)-(1)C(4)-Me-beta-D-Ribp2,3,4H(-3))] (5). The
      chiral sugar alcohols L-threitol (L-Thre) and D-arabitol (D-Arab) act as tetra-
      and pentadentate ligands, respectively, in (NEt(4))[Re(2)(CO)(6)(L-ThreH(
      3))]MeCN (6) and (NEt(4))(2)(DBUH)(2)[Re(6)(CO)(18)(D-ArabH(-5))(2)] (7).
      Complexes 6 and 7 are free of supporting oxo or methoxo ligands and use solely
      the O-atom pattern of the polyol for the connection of the Re(I)(CO)(3) moieties.

PMID- 16568492
TI  - Total synthesis of pteridic acids A and B.
AB  - Pteridic acid A (1) is a spirocyclic octaketide produced by the phytoepiphytic
      actinomycete Streptomyces hygroscopicus TP-A0451 and possesses potent plant
      growth-promoting activity comparable to that of indole-3-acetic acid. The
      enantioselective total synthesis of this natural product was achieved by
      employing the Sn(OTf)(2)-mediated Evans aldol reaction and the Fukuyama
      acetylenic coupling reaction as the key C--C bond-forming steps producing 1
      through a 14-step sequence in 22 % overall yield from a known oxazolidinone
      derivative. MgBr(2)-mediated equilibration of an anomerically favored spirocyclic
      intermediate used for the synthesis of 1 brought about partial epimerization of
      the spirocenter to give the corresponding anomerically disfavored epimer, which
      was converted into pteridic acid B (11-epi-1), another plant-growth promoter of
      the same microbial origin.

PMID- 16568493
TI  - A user-friendly, all-purpose Pd-NHC (NHC=N-heterocyclic carbene) precatalyst for
      the negishi reaction: a step towards a universal cross-coupling catalyst.
AB  - We have developed the first user-friendly Negishi protocol capable of routinely
      cross-coupling all combinations of alkyl and aryl centers. The use of an easily
      synthesized, air stable, highly active, well-defined precatalyst PEPPSI-IPr (1;
      PEPPSI=pyridine-enhanced precatalyst preparation, stabilization and initiation;
      IPr=diisopropylphenylimidazolium derivative) substantially increases the scope,
      reliability, and ease-of-use of the Negishi reaction. All organohalides and
      routinely used pseudohalides were excellent coupling partners, with the use of
      chlorides, bromides, iodides, triflates, tosylates, and mesylates resulting in
      high yield of the coupled product. Furthermore, all reactions were performed by
      using general laboratory techniques, with no glove-box necessary as the
      precatalyst was weighed and stored in air. Utilization of this methodology
      allowed for the easy synthesis of an assortment of sterically encumbered biaryls
      and druglike heteroaromatics, demonstrating the value of the PEPPSI-IPr system.
      Furthermore, this is also the first time Pd-NHC (NHC=N-heterocyclic carbene)
      methodology has surpassed the related phosphine-ligated Negishi processes both in
      activity and use.

PMID- 16568494
TI  - Easily prepared air- and moisture-stable Pd-NHC (NHC=N-heterocyclic carbene)
      complexes: a reliable, user-friendly, highly active palladium precatalyst for the
      Suzuki-Miyaura reaction.
AB  - The synthesis of NHC-PdCl(2)-3-chloropyridine (NHC=N-heterocyclic carbene)
      complexes from readily available starting materials in air is described. The 2,6
      diisopropylphenyl derivative was found to be highly catalytically active in alkyl
      alkyl Suzuki and Negishi cross-coupling reactions. The synthesis, ease-of-use,
      and activity of this complex are substantial improvements over in situ catalyst
      generation and all current Pd-NHC complexes. The utilization of complex 4 led to
      the development of a reliable, easily employed Suzuki-Miyama protocol. Employing
      various reaction conditions allowed a large array of hindered biaryl and drug
      like heteroaromatic compounds to be synthesized without difficulty.

PMID- 16568495
TI  - Induction of IgG antibodies against the GD2 carbohydrate tumor antigen by
      vaccination with peptide mimotopes.
AB  - The disialoganglioside GD2, a carbohydrate antigen, is expressed on all tumors of
      neuroectodermal origin, including melanoma, neuroblastoma, sarcoma and small cell
      lung cancer. Due to its specific expression on tumor surfaces, GD2 is an
      attractive target for immunotherapies. The mouse/human chimeric anti-GD2 mAb
      ch14.18 is already applied in melanoma and neuroblastoma trials as a passive
      immunotherapy. To establish an active immunotherapy alternative, we aimed to
      replace the poorly immunogenic ganglioside with immunogenic peptides. Previously,
      we used the ch14.18 antibody to select GD2 peptide mimics from a phage display
      library. In the present study, two mimics of the ch14.18 epitope were coupled to
      keyhole limpet hemocyanin and used for immunizing BALB/c mice. Induction of a
      specific humoral immune response towards the original antigen GD2, both purified
      and expressed on neuroblastoma and melanoma cells, could be demonstrated in
      ELISA, Western blot, and immunofluorohistochemistry. As the elicited antibodies
      were of the IgG isotype, the mimotope conjugates were capable of recruiting T
      cell help and inducing memory phenomena. In conclusion, we show that an epitope
      of the carbohydrate antigen GD2 can successfully be translated into immunogenic
      peptide mimotopes. Our immunization experiments indicate that GD2 mimotopes are
      suitable for active immunotherapy of GD2-expressing tumors.

PMID- 16568496
TI  - The Shiga toxin B-subunit targets antigen in vivo to dendritic cells and elicits
      anti-tumor immunity.
AB  - The non-toxic B-subunit of Shiga toxin (STxB) interacts with the glycolipid Gb3,
      which is preferentially expressed on dendritic cells (DC) and B cells. After
      administration of STxB chemically coupled to OVA (STxB-OVA) in mice, we showed
      that the immunodominant OVA(257-264) peptide restricted by K(b) molecules is
      specifically presented by CD11c+ CD8alpha- DC, some of them displaying a mature
      phenotype. Using mice carrying a transgene encoding a diphtheria toxin receptor
      (DTR) under the control of the murine CD11c promoter, which allows inducible
      ablation of DC, we showed that DC are required for efficient priming of CTL after
      STxB-OVA vaccination. Immunization of mice with STxB-OVA induced OVA-specific
      CD8+ T cells detected ex vivo; these cells were long lasting, since they could be
      detected even 91 days after the last immunization and were composed of both
      central and memory T cells. Vaccination of mice with STxB-OVA and STxB coupled to
      E7, a protein derived from HPV16, inhibited tumor growth in prophylactic and
      therapeutic experiments. This effect was mainly mediated by CD8+ T cells. STxB
      therefore appears to be a powerful carrier directly targeting DC in vivo,
      resulting in a strong and durable CTL response associated with tumor protection.

PMID- 16568499
TI  - Electron spin resonance study of radicals generated in cellulose/N
      methylmorpholine solutions after flash photolysis at 77 K.
AB  - The processes of radical formation in N-methylmorpholine-N-oxide monohydrate
      (NMMO) and cellulose/NMMO solutions were studied by ESR at 77 K under high-power
      UV (lambda = 248 nm) excimer laser flash photolysis. Radicals mainly generated
      were attributed to the nitroxide type radicals -CH2-NO*-CH2- and -CH2-NO*-CH3 at
      the first step and methyl *CH3 and formyl *CHO radicals at the second step of the
      photoreaction. Kinetic studies of these radicals revealed that formation and
      recombination rates of the radicals depend on the cellulose concentration in
      cellulose/NMMO solutions and the concentration of additional ingredients, e.g.
      Fe(II) and propyl gallate. Even at frozen state temperature, acceleration or
      quenching of radical reaction processes was found. The proposed scheme of UV
      light-induced NMMO degradation during irradiation based on ESR data correlates
      well with independently obtained results based on high-performance liquid
      chromatography (HPLC). The analysis of degradation products by HPLC, e.g.
      aminoethanol and acetaldehyde, supports the assumption concerning a radical
      initiated ring opening of NMMO.

PMID- 16568500
TI  - Influence of the spatial position of a trifluoromethyl group on the 13C chemical
      shifts in the cyclohexane series.
AB  - The influence of the introduction of a trifluoromethyl group on the 13C chemical
      shifts in cyclohexane was examined. The two main effects observed are located at
      the alpha and gamma positions relative to the carbon bearing the fluorine atoms.
      By comparison of the collected data it was possible to calculate the increments
      corresponding to the substitution of a hydrogen atom by a CF3 group at axial or
      equatorial positions on the cyclohexane ring.

PMID- 16568497
TI  - The key regulators of adult T helper cell responses, STAT6 and T-bet, are
      established in early life in mice.
AB  - Murine neonatal immunity is typically Th2 biased. This is characterized by high
      level IL-4 production at all phases of the immune response and poor IFN-gamma
      memory responses. The differential expression of Th1/Th2 cytokines by neonates
      and adults could arise if the critical regulators of Th differentiation and
      function, STAT6 and T-bet, operate differently during the neonatal period. To
      test this idea, the Th cell responses of wild-type, T-bet-deficient, or STAT6
      deficient mice were compared in vitro and in vivo. The absence of these factors
      had similar qualitative effects on the development of effector function in
      neonates and adults, i.e., if a Th lineage was inhibited or enhanced in adult
      animals, a similar phenomenon was observed in neonates. However, there was a
      striking difference observed in the in vivo Th1 memory responses of STAT6
      deficient mice initially immunized as neonates. Antigen-specific IFN-gamma
      production was increased 50-100-fold in STAT6-deficient neonates, achieving
      levels similar to those of STAT6-deficient adults. These findings demonstrate
      that STAT6 and T-bet signals are central in shaping Th responses in wild-type
      neonates, as in adult mice, and that the master regulators of Th cell development
      and function are already firmly established in early life.

PMID- 16568498
TI  - IL-18 stimulates IL-13-mediated IFN-gamma-sensitive host resistance in vivo.
AB  - IL-4 and IL-13 are up-regulated during in vivo responses to many nematode
      parasites, but increasing evidence suggests that increases in IL-13 can also
      occur independently of the IL-4-dominant Th2 response. Blocking B7 after
      Trichuris muris inoculation inhibits resistance and IL-4 elevations, instead
      resulting in an IFN-gamma-dominant response associated with susceptibility.
      However, blocking IFN-gamma under these conditions restores IL-13-dependent
      resistance. In this study, we examined the mechanism of IL-13 up-regulation and
      associated protection during this in vivo immune response. CD4+ T cells and DX5+
      TCR- cells were identified as the major producers of IL-13, and the DX5+ TCR-
      cells were phenotyped as NK cells, since they expressed CD11b, IL-2Rbeta and
      Ly49C but not c-kit or Fc epsilonRI. NK cell-derived IL-13 elevations were T cell
      dependent, as CD4+ T cell depletion blocked IL-13 production by mesenteric lymph
      node cells and induced susceptibility. IL-13 expression was increased
      independently of IL-12; however, blocking IL-18 function inhibited IL-13
      production and increased susceptibility. These results indicate that CD4+ T cells
      and NK cells are the major sources of IL-13 during the in vivo Th1 response
      induced by B7 blockade and that under these conditions, IL-18 is specifically
      required for the in vivo up-regulation of IL-13 production and associated host
      protection.

PMID- 16568501
TI  - A theoretical study of the possible use of electroosmotic flow to extend the read
      length of DNA sequencing by end-labeled free solution electrophoresis.
AB  - End-labeled free solution electrophoresis (ELFSE) provides a means of separating
      DNA with free-solution CE, eliminating the need for gels and polymer solutions
      which increase the run time and can be difficult to load into a capillary. In
      free-solution electrophoresis, DNA is normally free-draining and all fragments
      reach the detector at the same time, whereas ELFSE uses an uncharged label
      molecule attached to each DNA fragment in order to render the electrophoretic
      mobility size-dependent. With ELFSE, however, the larger molecules are not
      separated enough (limiting the read length in the case of ssDNA sequencing) while
      the smaller ones are overseparated; the larger ones are too fast while the
      shorter ones are too slow, which is the opposite of traditional gel-based
      methods. In this article, we show how an EOF could be used to overcome these
      problems and extend the DNA sequencing read length of ELFSE. This counterflow
      would allow the larger, previously unresolved molecules more time to separate and
      thereby increase the read length. Through our theoretical investigation, we
      predict that an EOF mobility of approximately the same magnitude as that of
      unlabeled DNA would provide the best results for the regime where all molecules
      move in the same direction. Even better resolution would be possible for smaller
      values of EOF which allow different directions of migration; however, the
      migration times then would become too large. The flow would need to be well
      controlled since the gain in read length decreases as the magnitude of the
      counterflow increases; an EOF mobility double that of unlabeled DNA would no
      longer increase the read length, although ELFSE would still benefit from a
      reduction in migration time.

PMID- 16568502
TI  - Silver staining method for DNA in polyacrylamide gels using eriochrome black T as
      a silver-ion sensitizer.
AB  - A sensitive silver staining method using eriochrome black T as a silver-ion
      sensitizer for DNA detection in polyacrylamide gels was developed. The
      sensitivity of this staining method was significantly improved by the new silver
      ion sensitizer containing a diazo group, which has reducing power. The staining
      method lasted a total of approximately 15 min following a fixing step for 2 x 20
      min. The detection limit of this staining method was 1-4 pg for PhiX174
      DNA/HaeIII in both nondenaturing and denaturing polyacrylamide gels. This
      staining method was especially effective in low-base pair DNA, with a sensitivity
      that was approximately ten-fold higher than previously published silver staining
      methods.

PMID- 16568503
TI  - Counterion-dye staining for DNA in electrophoresed gels using indoine blue and
      methyl orange.
AB  - In this study, we describe a sensitive staining method for DNA in agarose and
      polyacrylamide gels using organic visible dyes, indoine blue (IB) and methyl
      orange (MO). The counterion-dye staining method uses two oppositely charged dyes
      to form a hydrophobic ion pair complex in the staining solution. A decrease in
      the number of free forms of dyes in staining solution can enhance the selectivity
      of binding between the dye and DNA, and can reduce nonspecific background
      staining. As a result, the sensitivity of counterion-dye staining was
      significantly improved compared with other dye-based staining. This method uses a
      staining solution consisting of 0.008% IB, 0.002% MO, 10% ethanol and 0.2 M
      sodium acetate at pH 4.7, and can detect 5 ng of lambda DNA/HindIII within 60 min
      in agarose gels and 10 ng of PhiX174 DNA/HaeIII within 20 min in polyacrylamide
      gels.

PMID- 16568504
TI  - Sample sonication after trichloroacetic acid precipitation increases protein
      recovery from cultured hippocampal neurons, and improves resolution and
      reproducibility in two-dimensional gel electrophoresis.
AB  - Protein precipitation with TCA followed by acetone washing is frequently used to
      clean samples before 2-DE. However, the difficulty in solubilizing TCA
      precipitated proteins causes some variability in 2-D gels and makes it difficult
      to detect some proteins. In this work we show that sonication of the samples,
      after TCA precipitation followed by elution in sample buffer, increases total
      protein recovery, and improves reproducibility and matching ratios between gels
      when analyzed by specialized software.

PMID- 16568505
TI  - Treatment of rheumatoid arthritis patients with abatacept and methotrexate
      significantly improved health-related quality of life.
AB  - OBJECTIVE: This study examined the effect of abatacept, a costimulation
      modulator, on the health-related quality of life (HRQOL) of patients with
      rheumatoid arthritis (RA). METHODS: Three hundred thirty-nine patients with RA on
      a background of methotrexate (MTX), who participated in a multicenter, double
      blind, placebo-controlled trial, were randomized to abatacept 2 mg/kg, abatacept
      10 mg/kg, or placebo. HRQOL was assessed at pretreatment, and at 3, 6, and 12
      months posttreatment using the SF-36 Health Survey (SF-36). Changes in SF-36
      scores from baseline to 12 months were compared across treatment and placebo
      groups to examine HRQOL benefits of abatacept. A link between American College of
      Rheumatology improvement and changes in SF-36 scores was established to
      demonstrate the association between HRQOL outcomes and clinical response.
      RESULTS: After 12 months of treatment, patients randomized to abatacept 10 mg/kg
      showed significantly better HRQOL outcomes overall versus patients randomized to
      placebo (MANOVA F = 4.71, p < 0.001) or to abatacept 2 mg/kg (MANOVA F = 1.97, p
      = 0.05). Differences in SF-36 change scores between abatacept 10 mg/kg and
      placebo groups reached statistical significance on all 8 domain scales, the 2
      summary measures, and the SF-36 utility index (SF-6D). Differences in SF-36
      change scores between abatacept 10 mg/kg and abatacept 2 mg/kg reached
      statistical significance on 5 of the 8 domain scales, the physical summary
      measure, and the SF-6D. Improvement in HRQOL was highly related to clinical
      response. CONCLUSION Abatacept 10 mg/kg plus MTX demonstrated a stronger HRQOL
      response than placebo plus MTX. The abatacept 2 mg/kg arm showed a very weak and
      transient response.

PMID- 16568506
TI  - Community-based evaluation of etanercept in patients with rheumatoid arthritis.
AB  - OBJECTIVES: Etanercept is one of a new subgroup of biological disease modifying
      antirheumatic drugs (DMARD) to treat patients with rheumatoid arthritis (RA) who
      are non-responsive or intolerant to conventional DMARD. We evaluated the effects
      of etanercept (Enbrel) therapy in patients with RA in community-based clinical
      practice in Canada. METHODS: Using a cohort design, patients requesting
      etanercept therapy were stratified into treatment and control arms based upon
      their individual accessibility to obtain the drug. Patients were interviewed
      serially during a 12-month period of monitoring. The study measured painful or
      tender joint count, morning stiffness, pain severity, quality of life measures,
      medication utilization, health services utilization, and presence of adverse
      events. RESULTS: The baseline demographic and clinical variables for the
      treatment group (n = 223) and the control group (n = 208) were similar, except
      for education, income, and drug plan coverage. In followup, there was greater
      improvement in most clinical variables in the treatment arm compared to the
      control arm during the first 6 months, but the magnitude of difference between
      the 2 groups for some clinical variables decreased or became non-significant
      during the second 6 months. During the 12 month followup period there were 40
      (18%) patient dropouts in the treatment group. CONCLUSION: In a community based
      setting for the treatment of RA, etanercept can effectively improve the disease
      state, functional class, work disability, and quality of life during the first 6
      months of use. To determine the longterm sustainability of these effects studies
      with more than 12 months' duration will be required.

PMID- 16568507
TI  - The rolling belts injuries in childhood.
AB  - Rolling belt injuries are commonly seen in the summer when the tractors and water
      pumps work in agricultural fields. These machines' rolling belts may attract
      children and entrap their hands. The injuries frequently affect soft tissues and
      bone of volar side of their hands. Amputations may be seen. In the present study,
      45 patients with rolling belt injuries were retrospectively analysed. It was
      observed that 133 fingers of 42 patients and three hands (Zone III) of three
      patients were surgically treated. The treatment included primary closure of the
      lacerations, tendon/nerve repair, fixation of fractures, grafting, and local or
      cross-arm or groin flaps. Stump closure procedures were performed in 21 fingers
      with total amputations or non-viable tissues. The injuries in most of the cases
      were localised at Zones I and II. We performed revascularisation procedures in
      five fingers. Only one of them stayed alive (20%). Our results revealed that 13
      cases were good, 21 were fair and 11 were poor to according to Gorsche and Wood
      criteria. These injuries cause the burns and defects on digital arteries-veins as
      well as flexor tendons. Frequently, phalanx fractures and finger amputations may
      occur. Also, the skin defects are common. The treatment of rolling belt injuries
      is difficult, quite expensive, and the outcomes are not always satisfactory.

PMID- 16568508
TI  - Classification and treatment of hamate fractures.
AB  - Twenty-nine patients with hamate fractures were treated. The two main types of
      hamate fractures are hook fractures (type 1) and body fractures (type 2). We sub
      divided type 2 fractures according to the fracture line into coronal, type 2a and
      transverse, type 2b. There were 15 type 1, 11 type 2a and three type 2b
      fractures. For type 1, nine were treated with excision, one with open reduction
      and internal fixation (ORIF) and five with cast immobilisation, in which two
      resulted in non-union followed by excision. For type 2, five type 2a cases were
      treated with ORIF and the others with closed reduction and pinning. Most of the
      patients had satisfactory results at the seventh month follow-up. However, those
      with associated neurovascular and musculotendinous injuries were likely to have
      unfavourable results. On the basis of study findings, it appears that functional
      results are influenced mainly by the associated soft tissue damage.

PMID- 16568509
TI  - A novel artificial prosthetic replacement for the proximal interphalangeal joint
      of the hand--from concept to prototype.
AB  - This article describes the development of a proximal interphalangeal (PIP) joint
      prosthesis based on the principles of replicating anatomical surface components,
      the use of macrolocking intramedullary stem and the use of a cobalt-chrome alloy
      material. The design features are intended to obtain an optimal range of motion
      while retaining stability and longevity. The final prototype, for which a patent
      has been filed, is described.

PMID- 16568510
TI  - Functional results post-triangular fibrocartilage complex reconstruction with
      extensor carpi ulnaris with or without ulnar shortening in chronic distal
      radioulnar joint instability.
AB  - From September 1996 to September 2001, 37 adult patients were diagnosed with
      chronic triangular fibrocartilage complex (TFCC) tears with distal radioulnar
      joint (DRUJ) instability in our clinic. They had all received the procedure of
      TFCC reconstruction with partial extensor carpi ulnaris (ECU) combined with or
      without ulnar shortening. There were 36 males and one female in the study with a
      mean age of 22.4 years. The follow-up period ranged from 25 to 48 months with a
      mean of 36.2 months. All patients received the rehabilitation programme and were
      re-examined at our outpatient department. The results were graded according to
      the Mayo Modified Wrist Score. Eleven of the 37 patients rated their wrists
      "excellent", 22 rated "good", and four rated "fair". Overall, a total of 33
      patients (89%) rated satisfactorily and returned to work or sport activities.
      Therefore, TFCC reconstruction with partial ECU tendon combined with or without
      ulnar shortening procedure is an effective method for post-traumatic chronic TFCC
      tears with DRUJ instability suggested by this study.

PMID- 16568511
TI  - Lateral arm free flaps in the defects of the upper extremity--a review of 72
      cases.
AB  - Lateral arm flaps are versatile in the use of upper extremity moderate-sized
      defects with little morbidity and with acceptable cosmesis. The conditions are
      outlined in a series of 74 lateral arm flaps performed on 72 patients and the
      results are given. Five patients were operated on as emergencies, 12 were
      operated within the first 72 hours of injury and 57 patients were treated
      electively. Skin defects were between 6 x 4 cm and 20 x 9 cm. Five (7%) flaps
      were lost due to venous thrombosis, three that sustained a high-voltage electric
      burn. Two other patients that were treated for a high-voltage electric burn had a
      successful revision of the anastomosis site in the early post-operative duration.
      One flap was abandoned due to very thin pedicle and obesity of the patient. A
      higher failure rate is encountered most frequently with the cases of high-voltage
      electric burn. To deal with this problem, a modified approach such as an extended
      approach and/or including the forearm skin to the flap is recommended during the
      flap harvest. For a longer pedicle to be anatomized more proximally, perforator
      flaps with longer pedicles may be used as an alternative.

PMID- 16568512
TI  - Intra-articular loop wire fixation allows joint preservation and early motion in
      replantation around the proximal interphalangeal joint.
AB  - Restoration of motion is an important component of success in digital
      replantation. This is achieved only with rigid bony fixation that allows early
      post-operative mobilisation. In addition, the technique used should be simple and
      avoid excessive soft tissue stripping. These aims are difficult to achieve in
      amputations near the base of the proximal phalanx with existing bone fixation
      techniques. We describe a modification of the perpendicular loop wiring
      technique, where one wire loop is intra-articular, which satisfies the above
      criteria, and describe its application and results in two clinical cases.

PMID- 16568513
TI  - Adhesion formation after flexor tendon repair: comparison of two- and four-strand
      repair without epitendinous suture.
AB  - Increased handling, increased bulk at the repair site and an increase in external
      suture material may affect adhesion formation and gliding after tendon repair. A
      previous study(1) showed no significant difference in biomechanical or
      histopathological measurement of adhesion formation in two- and four-strand
      repairs combined with an epitendinous suture in the chicken model. In the present
      study, the flexor digitorum profundus tendon of the middle toe of 47 broiler
      chickens was cut and repaired with either a single (two-strand) or double (four
      strand) modified Kessler core suture without epitendinous suture and immobilised
      for four weeks. Adhesion formation was measured by biomechanical testing or
      quantitative and qualitative histopathology. Biomechanical and histological data
      showed no differences between two- and four-strand repairs. Results did not
      differ from the previous study which used an epitendinous suture. Adhesion
      formation is not necessarily increased when multi-strand techniques are used, nor
      by the placement of an epitendinous suture if care is taken with surgical
      technique. Individual healing response introduces more variability than an
      increase in tendon handling by an experienced surgeon.

PMID- 16568515
TI  - Trigger digits-associated carpal tunnel syndrome: relationship between carpal
      tunnel release and trigger digits.
AB  - Of 875 idiopathic carpal tunnel syndrome (CTS) cases, 101 (11.5%) required
      trigger digit release operations within three years before and/or after carpal
      tunnel release (CTR); these 101 cases were investigated, retrospectively. Trigger
      digit release (TDR) was performed most often after the CTR, especially within
      three months. Next most common was at the same time as the CTR. The TDR
      performance rate after CTR was 5.9%. The nerve conduction study (NCS) comparison
      between trigger digits-associated CTS and isolated CTS showed that pre-operative
      distal motor latency was significantly more delayed in trigger digits-associated
      CTS, while there was no evidence of any difference due to age or gender. The
      difference of operative method (open or endoscopic procedure) did not influence
      the incidence rate of trigger digits after the CTR. This study suggested that
      trigger digits-associated CTS has a previously developed wide-ranging narrowing
      of the flexor tendon sheath.

PMID- 16568514
TI  - The surgical treatment of the first carpometacarpal joint arthritis: evaluation
      of 400 consecutive patients treated by suspension arthroplasty.
AB  - Arthritis of the first carpometacarpal joint is a widespread disease in Western
      countries. It affects predominantly women with marked impairment in daily life
      activities. Its aetiopathogenesis is well described, while its treatment still
      controversial. The authors report their experience with 400 consecutive patients
      with established clinical and radiological findings of carpometacarpal joint
      arthritis treated by suspension arthroplasty with Ceruso's modified Weilby's
      technique. At 12 months follow-up, we were able to assess 315 patients using
      MAYO's score pre- and post-operatively, obtaining 86 excellent results, 134 good,
      62 fair and 33 poor. As for complications, there were seven infections, 32
      persistent pain and 42 limited range of motion. According to our experience the
      treatment modality of suspension arthroplasty with Ceruso's modified Weilby's
      technique represents the procedure of choice in indicated cases of first
      carpometacarpal joint arthritis in advanced stages according to Eaton-Littler
      classification.

PMID- 16568516
TI  - A simple method of osteosynthesis for avulsion fractures of the thumb
      metacarpophalangeal joint.
AB  - Five cases with an avulsion fracture of the thumb metacarpophalangeal joint
      treated by a simple method of internal fixation are described. This method is
      designed as a form of modified tension band wiring using the combination of a
      single Kirschner wire and a pull-out wire, and is technically easy.

PMID- 16568517
TI  - Clinical application of double dorsal plates for the distal radius fractures.
AB  - The purpose of this study was to develop plates that fit the contour of the
      distal radius of the Japanese and can be inserted less invasively. Three
      dimensional models of 36 radii of 18 volunteers were prepared. Using these
      models, the shape of the cortical bone on the radial margin of the distal radius
      and just below the dorsal fourth compartment of the wrist, to which the plates
      were expected to be applied, was measured, and the curves of the plates were
      determined. The functions of approximated curves of the plates were: [y = -2 x
      10(-8) x5 - 2 x 10(-6) x(4) + 0.0006 x3 - 0.0312 x2 + 0.3274 x + 15.224 on the
      radial margin of the distal radius and [y = 7 x 10(-7) x5 - 0.0001 x4 + 0.0078 x3
      - 0.2355 x2 + 3.1815 x - 5.6383 just below the fourth compartment. The clinical
      results of the application of double dorsal plates were satisfactory in clinical
      cases for the distal radius fractures.

PMID- 16568518
TI  - Mechanical strength and optimal site of placement of a threaded bone screw
      assessed on the basis of the screw breakage for non-union of the scaphoid: a
      biomechanical study.
AB  - We have performed the surgical procedure on the patients with the fracture of the
      scaphoid using mini-acutrak screws (ACUMED, Inc.). A 25-year-old man was injured
      in a fall. Surgical treatment for non-union of the scaphoid using a mini-acutrak
      screw was performed. However, this screw was broken, despite the absence of any
      obvious trauma mechanism. A structural examination was performed with a metal
      microscope and a hardness test was performed. A hardness evaluation was conducted
      on this broken screw and similar screws. Cannulated screws having diameters of
      2.7 and 3.5 mm were also evaluated in the strength test as controls for
      comparison. The breakage of screw occurred due to fatigue. The screw provides the
      strength equivalent to that of a 3.5 mm cannulated screw but the bending strength
      of the head end portion in which the breakage occurred was assumed to be the
      strength of about one-third that of the intermediate portion.

PMID- 16568519
TI  - Bone viability of amputated limbs treated with hypothermia: assessment by
      evaluation of mRNA levels.
AB  - We evaluated rat bone viability using a bone viability index (BVI). To evaluate
      hypothermic ischaemic bone injury, 21 amputated hind limbs of Fischer rats were
      preserved at hypothermia (4 degrees C) for 1, 3 and 6 hours. To evaluate
      hypothermic ischaemia/reperfusion injury, another 28 amputated limbs were
      transplanted to recipient rats after hypothermic ischaemia for 3 and 6 hours,
      respectively. Total RNA isolated from each tibia was fractionated by
      electrophoresis and hybridised with 32P-labelled cDNA of GAPDH, and the
      radioactivity of intact and degraded GAPDH mRNA measured. BVI was calculated as
      follows, BVI = [A / (A + B)] x 100, where A and B represent the radioactivities
      corresponding to intact and degraded GAPDH mRNA bands, respectively. In the
      hypothermic ischaemic insult group, BVIs were comparable to those of controls.
      However, in the 3-hour hypothermic ischaemia/reperfusion group, BVI was lower
      than that of the controls. Likewise, there was a significant difference between
      the 6-hour ischaemia/reperfusion group and controls. These results showed that
      bone viability decreased even after just a 3-hour hypothermic
      ischaemia/reperfusion.

PMID- 16568520
TI  - The "U-ligament" for collateral ligament reconstruction in duplicate thumb.
AB  - Duplicate thumb is a common congenital difference with complex management.
      Surgical treatment includes reconstruction of the collateral ligaments to
      optimise future function and cosmesis. We present the use of the "U-ligament" to
      further refine collateral ligament reconstruction. We have found it to be a
      simple and reliable technique.

PMID- 16568521
TI  - Treatments of osteoarthritis of the distal radioulnar joint: long-term results of
      three procedures.
AB  - Sixty-one wrists in 61 patients with osteoarthritis of the distal radioulnar
      joint treated by three consecutive procedures (20 Darrach, 25 Sauve-Kapandji and
      16 hemiresection-interposition arthroplastic procedures) were retrospectively
      evaluated. We preferred to perform Darrach's procedure in even the early stages
      of osteoarthritis of the distal radioulnar joint prior to introduction of Sauve
      Kapandji and hemirestion-interposition arthroplastic procedures. Subsequently the
      hemirestion-interposition arthroplasty was indicated when the triangular
      fibrocartilage cartilage was intact or could be reconstructed and the Sauve
      Kapandji when the triangular fibrocartilage complex could not be reconstructed or
      there was positive ulnar variance of more than 5 mm even though the triangular
      fibrocartilage complex was functional. Patient's age at operation averaged 59.8
      years. There were 36 men and 25 women. There were 38 primary and 23 secondary
      osteoarthritis cases. Post-operative pain, range of motion, grip strength, return
      to work status; and radiographic results were evaluated. At the five- to 14-year
      (average, ten years) follow-up evaluation, relief of pain from Darrach procedure
      was inferior to the Sauve-Kapandji procedure and hemiresection-interposition
      arthroplasty although this was not statistically significant. After both the
      Sauve-Kapandji procedure and hemiresection-inteposition arthroplasty, post
      operative improvements in flexion and extension of the wrist had statistical
      significance. Post-operative improvements in pronation and supination of the
      forearm showed statistical significances after all procedures. Improvements of
      post-operative grip strength and return to an original job in the Sauve-Kapandji
      procedure and hemiresection-interposition arthroplasty were statistically
      superior to those with a Darrach's procedure. There were many post-operative
      complications following the Darrach's procedure. Darrach's procedure is better
      indicated for severe osteoarthritic changes of the distal radioulnar joint in
      elderly patients. We believe the operative indications between the Sauve-Kapandji
      procedure and hemiresection-interposition arthroplasty are best determined prior
      to surgery by the existence and status of the triangular fibrocartilage complex
      and the amount of the positive ulnar variance.

PMID- 16568522
TI  - Paediatric Galeazzi-equivalent fracture: two case reports.
AB  - The authors present two rare cases of a paediatric Galeazzi-equivalent fracture.
      In contrast to Galeazzi's fracture-dislocation in adults, an epiphyseal
      separation of the distal ulna occurred instead of dislocation of the distal
      radioulnar joint (DRUJ) or both. A precise radiographic analysis of the
      epiphyseal separation of the distal ulna and its anatomical reduction were keys
      to obtaining a good result in the treatment of paediatric Galeazzi-equivalent
      fracture.

PMID- 16568523
TI  - A chronic nocardial infection following conservative treatment of a high pressure
      injection injury of air.
AB  - We present a case of recurrent cutaneous nocardiosis following a high pressure
      air injection injury which was treated conservatively. The patient subsequently
      developed multiple chronic granulomatous nodules in the palm and dorsum of the
      hand requiring repeated surgical debridements and long term antibiotics for
      complete resolution. Some reports suggest that high pressure injection injuries
      of air or water run a benign course and may be treated conservatively. However,
      inoculation by high pressure injection injury of air or water may result in
      chronic infections, which cause significant morbidity and are a therapeutic
      challenge. Although uncommon, they may be avoided by adherence to established
      treatment principles which include prompt recognition, realisation of its
      severity and aggressive treatment by open wound management, even for seemingly
      innocuous trauma or inoculum.

PMID- 16568524
TI  - Ulnar tunnel syndrome due to anatomical variant of the ulnar artery.
AB  - We report a case of ulnar tunnel syndrome due to an anatomical variant branch of
      the ulnar artery. Anatomical variants can cause compression not visible on
      imaging and need to be considered for successful surgical decompression.

PMID- 16568525
TI  - Total destruction of the fourth metacarpal bone by aneurysmal bone cyst:
      reconstruction with strut fibular graft--a case report.
AB  - Total destruction of the fourth metacarpal bone by aneurysmal bone cyst is
      presented. Despite the benign nature of the lesion on plain radiograms, magnetic
      resonance imaging (MRI) has revealed total destruction of metacarpal bone with
      shelling off the articular cartilages on both ends of the metacarpal. Both
      adjacent dorsal interosseous muscles were also involved with tumour. After
      removal of the metacarpal bone and third and fourth interossei, fibular
      bicortical strut graft was used for reconstruction. Arthrodesis was done both at
      the carpometacarpal and metacarpophalangeal (MCP) joints. The follow-up
      radiograms at one year revealed excellent incorporation of the graft with no
      evidence of local recurrence. A careful pre-operative work-up including MRI seems
      necessary even in lesions that look typically benign with intraosseous location
      on plain radiograms. This approach may prevent unpredicted morphologic picture
      during surgery, high recurrence rate and the number of operations.

PMID- 16568526
TI  - Simultaneous dorsal dislocation of the interphalangeal joints in ring finger with
      proximal interphalangeal joint dislocation of the middle finger: case report and
      review of the literature.
AB  - A 30-year-old amateur goalkeeper sustained simultaneous dislocation of the
      proximal and distal interphalangeal joints of the ring finger and of the proximal
      interphalangeal joint of the middle finger following a hyperextension injury.
      This was reduced under a local anaesthetic. Neighbour finger strapping and early
      mobilisation achieved an excellent functional outcome when reviewed at eight
      weeks after the initial injury.

PMID- 16568527
TI  - Simultaneous dislocations of the carpometacarpal joints: a case report.
AB  - A case of simultaneous dislocations of the carpometacarpal joints is reported.
      Closed reduction and splinting produced a good result.

PMID- 16568528
TI  - Vertical locking of the metacarpophalangeal joint of the thumb.
AB  - Locking of the metacarpophalangeal (MP) joint of the fingers, though reported
      infrequently, is not rare in the literature. We will report two rare cases of the
      MP joint of the thumb locked in 90 degrees of flexion (vertical locking). The
      first case is a 21-year-old man, punched on his right thumb by his friend, who
      arrived with his thumb fixed in a flexed position. The X-ray images of the right
      thumb showed the proximal phalanx subluxation in the palmer side in a vertical
      position. The second case is a 35-year-old woman with her right thumb
      accidentally caught in the chain of a key-holder. The locking was easily reduced
      without anaesthesia in both cases. We assume the mechanism was that the flexion
      force on the MP joint led to subluxation and the locking occurred due to the
      tension of the collateral ligament caused by the volar prominence of the radial
      condyle.

PMID- 16568530
TI  - Giant cell tumour of the distal phalanx of the hand.
AB  - Giant cell tumour of bone in the phalanx of the hand is extremely rare. A case of
      giant cell tumour of distal phalanx treated with a ray amputation is presented.

PMID- 16568529
TI  - Actinomycosis infection of the finger.
AB  - Actinomycosis is a rare cause of infection in the hand. We report a case of
      actinomycosis infection involving proximal phalanx, with the clinical
      presentation mimicking that of a bony neoplasm.

PMID- 16568531
TI  - Superficial radial nerve compression caused by a parosteal lipoma of proximal
      radius: a case report.
AB  - The superficial radial nerve might be compressed or injured at various anatomical
      sites along its course in the forearm. Most of the superficial radial nerve
      neuropathy are caused by pathological lesions such as trauma, a mass or tight
      band at the distal third of the forearm. Wartenberg's syndrome is the most common
      cause of sensory radial entrapment at the distal forearm. Compression of
      superficial radial nerve occurring at the proximal third of forearm is unusual.
      We present a rare case of superficial radial nerve compression due to a parosteal
      lipoma of proximal radius. Results of complete physical and radiological
      examinations are also presented. Surgical intervention of the tumour mass was
      performed for nerve decompression. The patient reported total relief of the
      neurological symptom post-operatively. This rare case demonstrates the unique
      characteristics of parosteal lipoma with unusual superficial radial nerve
      neuropathy at the proximal radius. This report reminds us that there is the
      possibility of superficial nerve compression caused by tumour mass over the
      proximal third of forearm.

PMID- 16568532
TI  - Physiolysis for correction of the delta phalanx in clinodactyly of the bilateral
      little fingers.
AB  - We report the results of long-term follow-up after Vickers' physiolysis of the
      trapezoidal delta phalanx in a boy aged five year and six months with bilateral
      clinodactyly of the little finger. Radial deviation of the little finger was
      corrected from 36 degrees to 15 degrees on the left, and from 35 degrees to 15
      degrees on the right at last follow-up six years and five months after surgery.
      The patient's parents were satisfied with the cosmetic appearance. X-ray film
      showed the abnormal distal epiphyses of the middle phalanges of the little
      fingers had disappeared.

PMID- 16568533
TI  - Abnormal ulnar nerve anatomy in the distal forearm pre-disposes to post-traumatic
      ulnar neuritis at the wrist.
AB  - Anatomical variations of the ulnar nerve have been described at the level of the
      elbow and in Guyon's canal, while the path in the forearm has always been assumed
      to be constant. We present a case of compressive ulnar neuropathy at the wrist
      pre-disposed by a presumed congenital variation of the path of the ulnar nerve at
      the level of the wrist which improved following surgical release of the
      constriction caused as a result of it.

PMID- 16568534
TI  - Extensor pollicis longus tendon rupture as a result of scapholunate dissociation:
      a case report.
AB  - A 39-year-old patient was presented with, to our knowledge, the first ever
      diagnosed case of extensor pollicis longus (EPL) tendon rupture as a result of
      scapholunate (S-L) dissociation. Arthroscopic findings showed that the dorsal
      aspect of the S-L ligament was ruptured and severe synovitis was revealed around
      the S-L joint. Direct observation revealed synovium at the rupture site of the
      EPL tendon. After careful resection of this synovium, an aperture in the S-L
      joint was observed. Thus, it was considered that the synovium in the S-L joint
      was connected to the rupture site of the EPL tendon, passing through the dorsal
      capsule of the S-L joint. The ruptured EPL tendon was reconstructed with extensor
      indicis proprius tendon transfer, and S-L dissociation was treated with a bone
      retinaculum-bone autograft taken from the third dorsal compartment region.

PMID- 16568535
TI  - Neurothekeomas of the upper limb--case series and clinicopathological review.
AB  - Neurothekeomas are rare, benign soft tissue tumours that are considered to be of
      nerve sheath origin. We present a case series of three patients who have
      neurothekeomas of the upper limb. There was a remarkably high tumour recurrence
      rate. The factors contributing to this outcome were studied and a
      clinicopathological review was performed.

PMID- 16568536
TI  - Irreducible chronic palmar dislocation of the distal radioulnar joint--a case
      report.
AB  - We report a rare case of irreducible chronic palmar dislocation of the distal
      radioulnar joint (DRUJ). This case showed that the dislocated ulnar head was
      impacted to the palmar cortex of the radius probably due to the dynamic force of
      the pronator quadratus muscle. Re-attachment of the ulnar styloid and partial
      resection of the ulnar head were necessary to make the reduction of the DRUJ
      possible. The continuity of the radioulnar ligament to the ulnar head was
      restored and the stability of DRUJ was maintained after reduction.

PMID- 16568537
TI  - Neural fibrolipoma of the ulnar nerve in the hand: a case report.
AB  - The author reports an unusual case of neural fibrolipoma (lipofibromatous
      hamartoma) of the ulnar nerve in the hand. A 20-year-old man presented with a
      fusiform soft tissue mass in his right hand. Neurological examination was normal
      except to minimal pain on palpation. Surgical exploration revealed that ulnar
      nerve and its digital branches were infiltrated by fibrofatty tissues. Fibrofatty
      tissues were dissected and removed from the nerve by microsurgical technique.
      Histological examination confirmed the diagnosis as a lipofibromatous hamartoma
      of the nerve. The result of surgical debulking was satisfactory.

PMID- 16568538
TI  - Extraskeletal chondroma as a cause of carpal tunnel syndrome: a case report.
AB  - We report a case of carpal tunnel syndrome as a result of an extraosseous
      chondroma in a 47-year-old gentleman. This case demonstrates the importance of
      clinical examination and occasional radiographs in this not uncommon condition.
      We also highlight that this well known entrapment syndrome is not only caused by
      the common causes that we all know, but also any space-occupying lesion in the
      carpal tunnel compressing the median nerve.

PMID- 16568539
TI  - Detecting and sorting targeting peptides with neural networks and support vector
      machines.
AB  - This paper presents a composite multi-layer classifier system for predicting the
      subcellular localization of proteins based on their amino acid sequence. The work
      is an extension of our previous predictor PProwler v1.1 which is itself built
      upon the series of predictors SignalP and TargetP. In this study we outline
      experiments conducted to improve the classifier design. The major improvement
      came from using Support Vector machines as a "smart gate" sorting the outputs of
      several different targeting peptide detection networks. Our final model (PProwler
      v1.2) gives MCC values of 0.873 for non-plant and 0.849 for plant proteins. The
      model improves upon the accuracy of our previous subcellular localization
      predictor (PProwler v1.1) by 2% for plant data (which represents 7.5% improvement
      upon TargetP).

PMID- 16568540
TI  - Protein threading with profiles and distance constraints using clique based
      algorithms.
AB  - With the advent of experimental technologies like chemical cross-linking, it has
      become possible to obtain distances between specific residues of a newly
      sequenced protein. These types of experiments usually are less time consuming
      than X-ray crystallography or NMR. Consequently, it is highly desired to develop
      a method that incorporates this distance information to improve the performance
      of protein threading methods. However, protein threading with profiles in which
      constraints on distances between residues are given is known to be NP-hard. By
      using the notion of a maximum edge-weight clique finding algorithm, we introduce
      a more efficient method called FTHREAD for profile threading with distance
      constraints that is 18 times faster than its predecessor CLIQUETHREAD. Moreover,
      we also present a novel practical algorithm NTHREAD for profile threading with
      Non-strict constraints. The overall performance of FTHREAD on a data set shows
      that although our algorithm uses a simple threading function, our algorithm
      performs equally well as some of the existing methods. Particularly, when there
      are some unsatisfied constraints, NTHREAD (Non-strict constraints threading
      algorithm) performs better than threading with FTHREAD (Strict constraints
      threading algorithm). We have also analyzed the effects of using a number of
      distance constraints. This algorithm helps the enhancement of alignment quality
      between the query sequence and template structure, once the corresponding
      template structure is determined for the target sequence.

PMID- 16568541
TI  - Algorithms for challenging motif problems.
AB  - Pevzner and Sze(19) have introduced the Planted (l,d)-Motif Problem to find
      similar patterns (motifs) in sequences which represent the promoter regions of co
      regulated genes, where l is the length of the motif and d is the maximum Hamming
      distance around the similar patterns. Many algorithms have been developed to
      solve this motif problem. However, these algorithms either have long running
      times or do not guarantee the motif can be found. In this paper, we introduce new
      algorithms to solve this motif problem. Our algorithms can find motifs in
      reasonable time for not only the challenging (9, 2), (11, 3), (15, 5)-motif
      problems but for even longer motifs, say (20, 7), (30, 11) and (40, 15), which
      have never been seriously attempted by other researchers because of the large
      time and space required. Besides, our algorithms can be extended to find more
      complicated motifs structure called cis-regulatory modules (CRM).

PMID- 16568542
TI  - Inferring phylogenetic relationships avoiding forbidden rooted triplets.
AB  - To construct a phylogenetic tree or phylogenetic network for describing the
      evolutionary history of a set of species is a well-studied problem in
      computational biology. One previously proposed method to infer a phylogenetic
      tree/network for a large set of species is by merging a collection of known
      smaller phylogenetic trees on overlapping sets of species so that no (or as
      little as possible) branching information is lost. However, little work has been
      done so far on inferring a phylogenetic tree/network from a specified set of
      trees when in addition, certain evolutionary relationships among the species are
      known to be highly unlikely. In this paper, we consider the problem of
      constructing a phylogenetic tree/network which is consistent with all of the
      rooted triplets in a given set C and none of the rooted triplets in another given
      set F. Although NP-hard in the general case, we provide some efficient exact and
      approximation algorithms for a number of biologically meaningful variants of the
      problem.

PMID- 16568543
TI  - Unique peptide identification of RNase A superfamily sequences based on
      reinforced merging algorithms.
AB  - Human ribonuclease A (RNaseA) superfamily consists of eight RNases with high
      similarity in which RNase2 and RNase3 share 76.7% identity. The evolutionary
      variation of RNases results in differential structures and functions of the
      enzymes. To distinguish the characteristics of each RNase, we developed
      reinforced merging algorithms (RMA) to rapidly identify the unique peptide motifs
      for each member of the highly conserved human RNaseA superfamily. Many motifs in
      RNase3 identified by RMA correlated well with the antigenic regions predicted by
      DNAStar. Two unique peptide motifs were experimentally confirmed to contain
      epitopes for monoclonal antibodies (mAbs) specifically against RNase3. Further
      analysis of homologous RNases in different species revealed that the unique
      peptide motifs were located at the correspondent positions, and one of these
      motifs indeed matched the epitope for a specific anti-bovine pancreatic RNaseA
      (bpRNaseA) antibody. Our method provides a useful tool for identification of
      unique peptide motifs for further experimental design. The RMA system is
      available and free for academic use at http://bioinfo.life.nthu.edu.tw/rma/ and
      http://spider.cs.ntou.edu.tw/bioinformatics/RMA.html.

PMID- 16568544
TI  - Direct prediction of T-cell epitopes using support vector machines with novel
      sequence encoding schemes.
AB  - New peptide encoding schemes are proposed to use with support vector machines for
      the direct recognition of T cell epitopes. The methods enable the presentation of
      information on (1) amino acid positions in peptides, (2) neighboring side chain
      interactions, and (3) the similarity between amino acids through a BLOSUM matrix.
      A procedure of feature selection is also introduced to strengthen the prediction.
      The computational results demonstrate competitive performance over previous
      techniques.

PMID- 16568545
TI  - The use of functional domains to improve transmembrane protein topology
      prediction.
AB  - Transmembrane proteins affect vital cellular functions and pathogenesis, and are
      a focus of drug design. It is difficult to obtain diffraction quality crystals to
      study transmembrane protein structure. Computational tools for transmembrane
      protein topology prediction fill in the gap between the abundance of
      transmembrane proteins and the scarcity of known membrane protein structures.
      Their prediction accuracy is still inadequate: TMHMM, the current state-of-the
      art method, has less than 52% accuracy in topology prediction on one set of
      transmembrane proteins of known topology. Based on the observation that there are
      functional domains that occur preferentially internal or external to the
      membrane, we have extended the model of TMHMM to incorporate functional domains,
      using a probabilistic approach originally developed for computational gene
      finding. Our extension is better than TMHMM in predicting the topology of
      transmembrane proteins. As prediction of functional domain improves, our system's
      prediction accuracy will likely improve as well.

PMID- 16568546
TI  - PRIMA: peptide robust identification from MS/MS spectra.
AB  - In proteomics, tandem mass spectrometry is the key technology for peptide
      sequencing. However, partially due to the deficiency of peptide identification
      software, a large portion of the tandem mass spectra are discarded in almost all
      proteomics centers because they are not interpretable. The problem is more acute
      with the lower quality data from low end but more popular devices such as the ion
      trap instruments. In order to deal with the noisy and low quality data, this
      paper develops a systematic machine learning approach to construct a robust
      linear scoring function, whose coefficients are determined by a linear
      programming. A prototype, PRIMA, was implemented. When tested with large
      benchmarks of varying qualities, PRIMA consistently has higher accuracy than
      commonly used software MASCOT, SEQUEST and X! Tandem.

PMID- 16568547
TI  - A new regulatory interaction suggested by simulations for circadian genetic
      control mechanism in mammals.
AB  - Knowledge of molecular biological systems is increasing at an amazing pace. It is
      becoming harder to intuitively evaluate the significance of each interaction
      between the molecules of the complex biological systems. Hence, we need to
      develop an efficient computational method to explore the biological mechanisms.
      In this study, we employed a hybrid functional Petri net in order to analyze
      mammalian circadian genetic control mechanisms, which consists of feedback loops
      of clock genes and generates endogenous near 24 h rhythms in mammals. We
      constructed a computational model based on the available biological data, and by
      using Genomic Object Net, we performed computer simulations of the time courses
      of clock gene transcription and translation. Although the original model
      successfully reproduced most of the circadian genetic control mechanisms, two
      discrepancies remained despite a wide selection of the parameters. We found that
      addition of a hypothetical path into the original model result in successful
      simulation of time courses and phase relationships among clock genes. This also
      demonstrates the usefulness of the hybrid functional Petri net approach to
      biological systems.

PMID- 16568548
TI  - High torsional energy disulfides: relationship between cross-strand disulfides
      and right-handed staples.
AB  - Redox-active disulfides are capable of being oxidized and reduced under
      physiological conditions. The enzymatic role of redox-active disulfides in thiol
      disulfide reductases is well-known, but redox-active disulfides are also present
      in non-enzymatic protein structures where they may act as switches of protein
      function. Here, we examine disulfides linking adjacent beta-strands (cross-strand
      disulfides), which have been reported to be redox-active. Our previous work has
      established that these cross-strand disulfides have high torsional energies, a
      quantity likely to be related to the ease with which the disulfide is reduced. We
      examine the relationship between conformations of disulfides and their location
      in protein secondary structures. By identifying the overlap between cross-strand
      disulfides and various conformations, we wish to address whether the high
      torsional energy of a cross-strand disulfide is sufficient to confer redox
      activity or whether other factors, such as the presence of the cross-strand
      disulfide in a strained beta-sheet, are required.

PMID- 16568549
TI  - Stroke risk high in first month after heart attack.

PMID- 16568550
TI  - Proteomics. Health at the cellular level.

PMID- 16568551
TI  - If stomach acid helps digest food, how is food digested if you take an antacid
      after a meal?

PMID- 16568552
TI  - I've had a couple of painful gout attacks. My doctor says they're related to high
      levels of uric acid in my blood. My doctor also says that increased uric acid
      might mean a higher risk of heart problems. Are uric acid levels usually checked?

PMID- 16568553
TI  - Thallium-201 versus Tc99m-glucoheptonate SPECT for evaluation of recurrent brain
      tumours: a within-subject comparison with pathological correlation.
AB  - BACKGROUND: Thallium-201 (Tl-201) is the most commonly used tracer for functional
      imaging of recurrent brain tumours. However, the physical properties of Tl-201
      are not particularly suitable for this application, thus, a technetium-99 (Tc99m)
      labelled alternative with more favourable physical properties has been sought.
      The aim of this study was to compare the ability of Tl-201 and Tc99m
      glucoheptonate single photon emission computed tomography (SPECT) to detect
      viable recurrent tumour and differentiate post-radiation gliosis. METHOD: Brain
      SPECT with Tl-201 and Tc99m-glucoheptonate was performed in 20 patients with
      malignant brain tumour in whom recurrent disease was suspected. Tracer uptake in
      the mass was defined as high, moderate or low and was correlated with
      histological verification of the lesion in all cases. RESULTS: Recurrent tumour
      was demonstrated in 17 patients by both Tl-201 and Tc99m-glucoheptonate SPECT and
      confirmed by surgical resection in all 17 patients. Three patients had no tracer
      uptake on either Tl-210 or Tc99m-glucoheptonate SPECT and surgical resection
      revealed only fibrotic tissue with areas of necrosis. Tc99m-glucoheptonate images
      were found to correlate more closely with the surgical findings with regard to
      the location of tumour margin, extent of tumour invasion and intratumoural
      necrosis. CONCLUSION: Tc99m-glucoheptonate brain SPECT is an accurate agent for
      SPECT imaging of recurrent brain tumours and may provide more information about
      the location of the tumour margin and its extent and intratumoural necrosis than
      Tl-201. Tc99m-glucoheptonate may be a viable replacement for Tl-201.

PMID- 16568554
TI  - Images in neuroscience. Tectal arteriovenous malformation.

PMID- 16568555
TI  - Images in neuroscience. Acute confusion and agitation after epidural anaesthesia.

PMID- 16568556
TI  - Rising tensions boost humanitarian concern for Palestinians.

PMID- 16568557
TI  - Middle-Eastern AIDS efforts are starting to tackle taboos.

PMID- 16568558
TI  - A snapshot of medical journals from the Middle East.

PMID- 16568560
TI  - Percutaneous transhepatic balloon dilation for portal venous stenosis.

PMID- 16568561
TI  - Hemochromatosis and liver transplant survival.

PMID- 16568563
TI  - Selling ourselves.

PMID- 16568562
TI  - Infection by proxy: the role of chimeric mice in HBV and HCV research.

PMID- 16568564
TI  - Actors as teachers.

PMID- 16568565
TI  - Maturing out of alcohol dependence: the impact of transitional life events.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of
      transitional life events related to education, employment, and family formation
      on the likelihood of recovery from alcohol dependence as defined by the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV),
      distinguishing the short- and long-term effects of these events and potential
      effect modification by treatment history, gender, and severity of dependence.
      METHOD: This analysis is based on data from the Wave 1 2001-2002 National
      Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a cross
      sectional, retrospective survey of a nationally representative sample of U.S.
      adults 18 years of age and older. The analytic sample consisted of 4,422
      individuals with prior-to-past-year (PPY) onset of DSM-IV alcohol dependence.
      Time-dependent proportional hazards models were used to estimate the effects of
      completing school, starting full-time work, getting married, becoming
      separated/divorced/widowed, and becoming a parent on the outcomes of nonabstinent
      recovery (NR; e.g., low-risk asymptomatic drinking) and abstinent recovery (AR).
      RESULTS: Entry into and exit from a first marriage each increased the likelihood
      of NR during the first 3 years after those events occurred (hazard rate ratio
      [HRR] = 1.37 and 1.76, respectively). However, individuals who were still
      dependent 3 or more years after those events occurred had a decreased likelihood
      of subsequent NR (HRR = 0.70 for both events), as did those who were still
      dependent 3 or more years after completing schooling (HRR = 0.54). The likelihood
      of AR was more than doubled in the 3 years after first becoming a parent (HRR =
      2.22) but was decreased among individuals still dependent 3 or more years after
      starting full-time work. For the outcome of NR, all of the negative effects
      associated with still being dependent 3 or more years after the occurrence of key
      life events were more strongly negative among individuals with less severe cases
      of dependence. CONCLUSIONS: Transitional life events demonstrate many effects on
      recovery, including both direct effects consistent with role socialization and
      associations more reflective of selectivity than causation. Taken as a whole,
      these events appear to contribute to (but by no means fully explain) the high
      rates of recovery from alcohol dependence that have been observed even in the
      absence of treatment.

PMID- 16568566
TI  - GP management of dyspepsia.

PMID- 16568568
TI  - Adapting to hope and uncertainty: two decades of Focus.

PMID- 16568567
TI  - [Holmium: YAG laser lithotripsy under ureteroscopy for treating urinary caluli
      combined with acute renal failure].
AB  - OBJECTIVE: To evaluate the therapeutic effect and safety of holmium:YAG laser
      lithotripsy for treating ureteral calculi combined with acute renal failure.
      METHODS: Ureteroscopic holmium: YAG laser lithotripsy was used in 13 cases of
      ureteral calculi. RESULTS: After the operation the serum Bun and Cr levels in the
      patients decreased to different degrees or returned to normal and the stone free
      rate was up to 92.3% (12/13). CONCLUSION: The ureteroscopic holmium:YAG laser
      lithotripsy can be the first choice for the upper urinary tract obstruction
      associated with acute renal failure,due to its safety and efficiency. It can also
      deal with the double sites of ureteral diseases.

PMID- 16568570
TI  - [Autoimmune epilepsy].

PMID- 16568569
TI  - [A ten-year old boy with progressive neurologic outcome].
AB  - BACKGROUND: Rasmussen's encephalitis is a rare chronic inflammatory disease with
      unknown etiology. Patients with this condition have symptoms of intractable
      partial epilepsy, often with epilepsia partialis continua combined with a
      progressive hemiparesis. MATERIAL AND METHODS: The history of a Norwegian ten
      year old boy with Rasmussen's encephalitis is described. RESULTS AND
      INTERPRETATION: The patient had clinical symptoms of Rasmussen's encephalitis. He
      had intractable partial epilepsy including epilepsia partialis continua. Cerebral
      MRI showed unilateral right-sided cerebral atrophy and foci of increased signal
      intensity in cortical grey and subcortical white matter. The boy was operated
      with right-sided hemispherectomy and is postoperatively seizure free. To our
      knowledge, this is the first published Norwegian child with Rasmussen's
      encephalitis. The disorder may be underdiagnosed in Norway. It is important to
      recognise this disease as early as possible.

PMID- 16568571
TI  - Understanding tolerable upper intake levels. Proceedings of a workshop. April 23
      24, 2003. Washington, DC, USA.

PMID- 16568572
TI  - The Oncology Nursing Certification Corporation responds.

PMID- 16568573
TI  - Health aspects of the Tsunami disaster in Asia. Proceedings of a conference
      convened by the World Health Organization. May 4-6, 2005. Phuket, Thailand.

PMID- 16568575
TI  - Atopic eczema - new insights in the definition, diagnostics and disease
      management. Proceedings of a LEO eczema workshop. November 2003. Copenhagen,
      Denmark.

PMID- 16568574
TI  - Mastering reimbursement: basic CPT code selection.

PMID- 16568576
TI  - SIMEC 2004. Proceedings of the 8th Brazilian Symposium on Extracellular Matrix
      and the 3rd International Symposium on Extracellular Matrix. September 27-30,
      2004. Angra dos Reis, RJ, Brazil.

PMID- 16568579
TI  - Abstracts of the Annual Conference of the Swiss Society for Allergology and
      Immunology, Zurich, March 30-31, 2006.

PMID- 16568577
TI  - Abstracts from the International Congress XIX on Endovascular Interventions,
      February 12-16, 2006.

PMID- 16568578
TI  - Abstracts of the 48th Annual Meeting of the Endocrine Society of Australia,
      Perth, Australia, September 2005.

PMID- 16568580
TI  - Osteoporosis-an update.
AB  - Osteoporosis is a systemic disease characterized by decrease in bone mass per
      unit volume, compromised bone strength, which predisposes the affected bone to
      fracture. This is currently one of the leading causes of morbidity and mortality
      among elderly over the world. In general, osteoporosis is a silent and
      progressive disorder that is often brought to attention of the patients or
      physician only after a fracture. The aetiology of osteoporosis is multifactorial
      and is related to two main processes: acquisition of peak bone density that
      occurs at the end of the third decade and loss of bone at menopause, going on to
      old age. The cardinal features of osteoporosis are pain, fracture and deformity.
      Bone mineral density measurement is the most reliable diagnostic tool in the
      early stage of osteoporosis. Management of osteoporosis involves prevention and
      treatment. The best treatment for osteoporosis is prevention. The risk of
      osteoporosis can be reduced by increasing peak bone mass or by decreasing the
      bone loss. It needs to be emphasized that bone mineral density (BMD) peaks at
      about age 35 and then begins to slowly decline with significant acceleration
      after menopause.Therefore, the most logical and cost-effective preventive
      strategies are to encourage young women to stop smoking and avoid excessive use
      of alcohol. They should also be counseled to exercise regularly and consume
      adequate amounts of calcium and vitamin D.

PMID- 16568581
TI  - Abstracts of the 10th Biennial Meeting of the Asia Pacific Society for Sexual
      Medicine (APSSM), October 4-8, 2005.

PMID- 16568582
TI  - Position of the American Dietetic Association: food insecurity and hunger in the
      United States.
AB  - It is the position of the American Dietetic Association that systematic and
      sustained action is needed to bring an end to domestic food insecurity and hunger
      and to achieve food and nutrition security for all in the United States. The
      Association believes that immediate and long-range interventions are needed,
      including adequate funding for and increased utilization of food and nutrition
      assistance programs, the inclusion of food and nutrition education in all
      programs providing food and nutrition assistance, and innovative programs to
      promote and support the economic self-sufficiency of individuals and families, to
      end food insecurity and hunger in the United States. Food insecurity continues to
      exist in the United States, with over 38 million people experiencing it sometime
      in 2004. Negative nutritional and nonnutritional outcomes have been associated
      with food insecurity in adults, adolescents, and children, including poor dietary
      intake and nutritional status, poor health, increased risk for the development of
      chronic diseases, poor psychological and cognitive functioning, and substandard
      academic achievement. Dietetics professionals can play a key role in ending food
      insecurity and hunger and are uniquely positioned to make valuable contributions
      through provision of comprehensive food and nutrition education, competent and
      collaborative practice, innovative research related to accessing a safe and
      secure food supply, and advocacy efforts at the local, state, regional, and
      national levels.

PMID- 16568583
TI  - Understanding and using the scope of dietetics practice framework: a step-wise
      approach.

PMID- 16568584
TI  - Nutrition fact sheet: dietary fiber: an important link in the fight against heart
      disease.

PMID- 16568585
TI  - Lessons from our leaders: advancing oncology nursing through the power of the
      group.

PMID- 16568586
TI  - Reader asks Oncology Nursing Forum and Clinical Journal of Oncology Nursing
      editors about terminology.

PMID- 16568587
TI  - Assessing and addressing erectile function concerns in patients
      postprostatectomy.

PMID- 16568588
TI  - Disabled...or otherwise enabled?

PMID- 16568589
TI  - Medicare Part D.

PMID- 16568590
TI  - Rekindling the fire, continued.

PMID- 16568591
TI  - Rekindling the fire, continued.

PMID- 16568592
TI  - Rekindling the fire, continued.

PMID- 16568593
TI  - Medical necessity and level-IV visits.

PMID- 16568594
TI  - Coding & documentation.

PMID- 16568595
TI  - Creating a high-performing clinical team.

PMID- 16568596
TI  - EHRs in the exam room: tips on patient-centered care.

PMID- 16568597
TI  - Patient balances: getting to the root of the problem.

PMID- 16568599
TI  - How consumer-driven health plans will affect your practice.

PMID- 16568598
TI  - Implementing open-access scheduling in an academic practice.

PMID- 16568600
TI  - [O. V. Palladin--patriarch of neurochemical science (on the 120th birthday of
      academician Oleksandr Volodymyrovych Palladin)].
AB  - The paper is dedicated to Academician Oleksandr Volodymyrovych Palladin (1895
      1972), a founder of neurochemical school in Ukraine. The problem of biochemistry
      of the nervous system has been developed in Ukraine since the 20's of the 20th
      century. Theoretical principles and prospects of development of the basic trends
      in neurochemistry were stated for the first time in the paper by O. V. Palladin-
      the first work in biochemistry of the nervous system in Ukraine--"Biochemistry of
      the Brain and Psychochemistry", published in the journal "Nauka v Ukraine"
      ("Science in Ukraine") in 1922. Researches in neurochemistry have been carried
      out systematically since 1925 at the Ukrainian Biochemical Institute founded and
      headed by O. V. Palladin (O. V. Palladin Institute of Biochemistry, now). During
      the following period of half a century O.V. Palladin and his disciples made
      original works in the field of chemical topography of the nervous system,
      functional neurochemistry, in particular, in the field of protein and nitrous,
      lipid, nucleic metabolism, transmembrane transport of ions and metabolites, etc.
      Results of long-term investigations were reported at numerous international
      physiological and biochemical congresses, All-Union and Ukrainian biochemical
      conferences, seminars and have acquired the world fame. O. V. Palladin's great
      deserts in development of biochemistry of the nervous system were recognized and
      he was proclaimed a "patriarch" of the world neurochemistry at the first congress
      of the International Neurochemical Society in Strassburg (1967) and awarded a
      Gold Medal--one of the four delivered at the Second Congress of this Society in
      Milan (1969).

PMID- 16568601
TI  - [Protein splicing].
AB  - Inteins are internal polypeptide sequences that are posttranslationally excised
      from a protein precursor by a self-catalyzed protein-splicing reaction. Most of
      inteins consist of N- and C-terminal protein splicing domain and central
      endonuclease domain. The endonuclease domain can initiate mobility of the intein
      gene, this process being named intein homing. This review is focused on the
      recent data about the structure and function of inteins. Main intein-mediated
      protein-engineering applications, such as protein purification, ligation and
      cyclization, new forms of biosensors, are presented.

PMID- 16568602
TI  - [Vitamine-like substances L-carnitine and acetyl-L-carnitine: from biochemical
      studies to medicine].
AB  - Recently reported data clarify our understanding of the molecular aspects of
      carnitine in medicine. Carnitine is a compound necessary for the transport of
      acyl-CoA across the inner mitochondrial membrane for their beta-oxidation. Only L
      isomer of carnitine is biologically active. The D-isomer may actually compete
      with L-carnitine for absorption and transport, increasing the risk of carnitine
      deficiency. By interaction with CoA, carnitine is involved in the intermediary
      metabolism by modulating free CoA pools in the cell. Detoxification properties
      and anabolic, antiapoptotic and neuroprotective roles of carnitine is presented.
      Carnitine deficiency occurs as a primary genetic defect of carnitine transport
      and secondary to a variety of genetic and acquired disorders. The
      pathophysiological states associated with carnitine deficiency have been
      summarized. L-Carnitine is effective for the treatment of primary and secondary
      carnitine deficiencies. Acetyl-L-carnitine improves cognition in the brain,
      significantly reversed age-associated decline in mitochondrial membrane potential
      and improved ambulatory activity. The therapeutic effects of carnitine and
      acetylcarnitine are discussed.

PMID- 16568603
TI  - [The thiazole derivative reduces transmembrane currents via ionic channels formed
      by alpha-latrotoxin and sea anemone toxin in the bilayer lipid membranes].
AB  - It was shown that the thiazole derivative 3-decyloxycarbonylmethyl-4-methyl- 5-(2
      hydroxyethyl)thiazole chloride (DMHT) (0.1 mM) reversibly reduced the
      transmembrane current in solutions of 10 mM CaCl2 and 100 mM KCl via ionic
      channels produced by alpha-latrotoxin from black widow spider (alpha-LT) and sea
      anemone toxin (RTX) in the bilayer lipid membranes (BLM). Introduction of DMHT
      from the cis-side of BLM inhibited transmembrane current by 31.6 +/- 3% and by
      61.8 +/- 3% from the trans-side of BLM for alpha-LT channels. Application of DMHT
      to the cis-side BLM decreased the inward current through the RTX channels by 50
      +/- 5%. Addition of Cd(2+) (0.1 mM) to the cis- or trans-side of a membrane after
      the DMHT induced depression of transmembrane current across the alpha-LT channels
      caused its further decrease by 85 +/- 5% that coincides completely with the
      intensity of Cd(2+)-inhibition in the control experiments without DMHT. These
      data suggest that DMHT may exert its inhibitory action on alpha-LT channels
      without considerable influence on the ionogenic groups inside the channel cavity.
      The comparative analysis of effective radii measured for alpha-LT and RTX
      channels on the cis- (0.9 nm and 0.55 nm, respectively) and the trans-side of BLM
      (< 0.467 nm for alpha-LT) allowed to propose the blocking action of DMHT for
      alpha-LT and RTX channels to result from direct penetration into the channel,
      achieved due to similar hydrodynamic size of blocking molecules and the size of
      toxin pores.

PMID- 16568604
TI  - [Function of reconstituted into liposomes Ca(2+)-transporting ATPase of the
      smooth muscle cell plasma membrane in the presence of transmembrane Na+
      gradient].

PMID- 16568605
TI  - [Composite matrix membranes as synthetic receptor systems. 2. Structural
      morphological characteristics].
AB  - Structural and morphological characteristics of composite imprinted membranes for
      selective recognizing of adenosine 3',5'-cyclic monophosphate (cAMP) were
      studied. Composite polyvinylidene fluoride microfiltration membranes (Millipore)
      covered with a thin imprinted polymer layer were prepared using photoinitiated
      copolymerization of dimethylaminoethylmetacrylate with
      trimethylolpropanethrimethacrylate in the presence of cAMP as template. Atomic
      force microscopy (AFM) and scanning electron microscopy (SEM) were used to
      visualise surfaces and cross-sections of imprinted membranes and to determine
      their structural and morphological parameters such as pore size, thickness of
      selective imprinted layer, surface roughness as well as total surface contact
      area. The impact of structural characteristics on separation properties of the
      imprinted membranes was analyzed. It was found out that the thickness of the
      imprinted polymer layer with optimal recognizing properties is limited.

PMID- 16568606
TI  - [Berberine and amitozine binding with calf thymus DNA].
AB  - Binding of amitozine and berberine to DNA has been investigated by VIS- and UV
      spectroscopy. It has been found that amitozine forms one type of complex and
      berberine forms two types of complexes with DNA. Observed concentration
      dependences of absorption spectra were analyzed using the DALSMOD optimization
      program and association constants were calculated (K(BCl)= 3 x 10(3) M(-1), K(Am)
      = 1.6 x 10(3)-10(4) M(-1)). Competitive binding of berberine to DNA in presence
      of ethidium bromide has been investigated as well. It has been shown that it
      competes with berberine for DNA binding sites.

PMID- 16568607
TI  - [Cytotoxic effect of vitamin E short-chain derivatives on rat thymocytes].
AB  - It is established, that alpha-tocopherol, alpha-tocopheryl acetate and tocopheryl
      quinone with carbon lateral chains shortened to 6 atoms inhibited the viability
      of primary culture rats thymocytes in a dose-dependent manner. Absence of the DNA
      internucleosomal degradation side by side with cytosolic lactate-dehydrogenase
      outlet from the cells testifies to the benefit of necrotic way of thymocytes
      destruction. The outlet from cells of acid phosphatase, lysosomal marker enzyme,
      testifies to destabilization of lysosomal membranes by the researched compounds.
      The possible mechanism of cytotoxication of vitamin E short-chain derivatives in
      cell cultures is offered, namely: their high permeability through a plasmatic
      membrane allows to create inside the cells a concentration, sufficient for
      detergent-like rupture of the lysosomal membranes, that results in the entering
      of lysosomal enzymes in cytosol and destruction of cells by necrosis.

PMID- 16568608
TI  - Some signal effects in human erythrocytes on specific binding of free doxorubicin
      and doxorubicin conjugates with magnetite nanoparticles.
AB  - Binding of doxorubicin (DOX) immobilized on nanodispersed magnetite (DOX-M
      conjugates with loading in the range of 0.16-25.1 mg DOX/g carrier) to intact
      human erythrocytes in concurrence with free DOX was investigated. Two specific
      binding sites for doxorubicin were revealed at the plasma membrane of human
      erythrocytes. Changes in the ordering of the DOX-M nanoparticles according to
      small angle scattering data are consistent with their specific binding at the
      plasma membrane upon incubation with erythrocytes. Free and conjugated
      doxorubicin modulated signal transduction in erythrocytes in a similar way. Both
      up-regulate nitric oxide and cyclic GMP and down-regulate cyclic AMP production
      and stabilize the membranes of oxidatively damaged erythrocytes.

PMID- 16568610
TI  - [Role of heparin in the formation of food lipemia].
AB  - Influence of endogenic and exogenic heparin in vivo on the basic forms of serum
      lipids content: cholesterol ethers, triacylglycerols, free fatty acids; as well
      as that glycosaminoglycan effect in vivo and in vitro on total lipoproteine
      lipase (LPL) activity and lecithin-cholesterol acyltransferase (LCAT) activity of
      human blood serum were investigated on food lipidemia model. The decrease of
      intercell reserve heparin content and increase of the background and post-heparin
      levels of blood serum LPL activity were indicated after two hours food load. The
      role of two factors, endogenic heparin being one of them, in the increase of
      postprandial LPL activity of blood serum were discussed. At the same time, some
      inhibition of blood serum LCAT activity two hours after food reception
      (evidently, as a result of endogenic heparin action) and to a considerable extent
      inhibition of cholesterol etherification under the action of exogenic heparin in
      vivo were ascertain. Heparin in vitro (50 U/ml of blood serum) did not influence
      LCAT and total LPL activities. It was summarised that endogenic heparin is a
      factor, taking part in lipolysis processes regulation.

PMID- 16568609
TI  - [Survival and antioxidant defence of the yeast Saccharomyces cerevisiae during
      starvation and oxidative stress].
AB  - The role of catalase in response of the yeast Saccharomyces cerevisiae to
      oxidative stress induced by hydrogen peroxide under starvation was investigated.
      It was shown that under conditions used in this study 0.5 mM H2O2 did not change
      the number of viable cells in the wild strain YPH250, but this parameter was
      decreased by 15% in the acatalsaemic strain YWT1. Cells treatment with 0.5 mM
      H2O2 for 30 min did not modify the levels of carbonyl proteins in the parental
      strain, but caused its 1.4-fold increase in the defective strain. The observed
      1.5-fold activation of catalase in the wild strain cells in response to H2O2
      stress suggests that under starvation conditions catalase can be involved in the
      yeast cell protection, particularly they can prevent oxidative modification of
      some antioxidant and associated enzymes.

PMID- 16568611
TI  - [Effect of nicotinamide on the reactions of peroxide oxidation of biomolecules in
      the rat brain and erythrocytes in 1,2-dichloroethane toxic injury].
AB  - It was established that acute poisoning of rats by 1,2-dichloroethane induced
      considerable changes in lipid peroxidation indices, glutathione content and
      activity of antioxidant enzymes--superoxidase, catalase, glutathione peroxidase
      in the brain tissue, erythrocytes and blood plasma. It was shown that
      nicotinamide in the dose of 200 mg/kg prevented considerable degree of the
      intoxication caused by 1,2-dichloroethane as well as activation of lipid
      peroxidation and inhibition of antioxidant defens enzyme activities in tissue of
      experimental animals.

PMID- 16568612
TI  - Age-related effects of methionine-enriched diet on plasma homocysteine
      concentration and methylation of hepatic DNA in rats.
AB  - In the present study we determined the age-related effect of methionine-enriched
      diet, a model of hyperhomocysteinemia, on the level of plasma homocysteine and
      hepatic global DNA methylation in rats. Feeding methionine diet to middle-aged
      rats for only 14 days resulted in a significant increase in plasma homocysteine
      level and DNA hypomethylation. In contrast, feeding the methionine-containing
      diet for 2 weeks to juvenile or post-pubertal animals did not alter the level of
      plasma homocysteine or hepatic DNA methylation. Supplementation of the methionine
      enriched diet with vitamins B6, B12 and folic acid prevented both hepatic DNA
      hypomethylation and an increase of plasma homocysteine concentration in the
      middle-aged rats. These findings indicate that the elevated level of plasma
      homocysteine may be indicative of much broader and deeper alterations in
      intracellular methylation dysfunction, and suggest that dietary enrichment with B
      vitamins is essential for the metabolism of homocysteine, especially in adult
      animals.

PMID- 16568613
TI  - [Sodium azide as indirect nitric oxide donor: researches on the rat aorta
      isolated segments].
AB  - A comparative investigations of heme-containing enzymes inhibitors NaN3 and NaCN
      effects on the rat aorta isolated segments tone has shown that NaN3 in the range
      of very low concentrations from 10(-9) to 10(-6) M displays pharmacological
      activity characteristic of nitric oxide (NO) donors, which is inhibited by NaCN.
      The value of vasodilatation, caused by NaN3, was also decreased in the presence
      of soluble guanylate cyclase inhibitor ODQ (10(-5) M). It was found that H2O2
      injection to physiological solution containing NaN3 and horseradish peroxidase or
      catalase lead to NO2- accumulation in it, which was blocked by NaCN. The
      nonenzymic NaN3 oxidization by hydrogen peroxide was not found in control
      experiments. NaN3 physiological activity dependent on NO-donating properties of
      this traditional inhibitor of heme-containing enzymes is discussed.

PMID- 16568614
TI  - [Active nitrogen and oxygen metabolites change cAMP level in the uterus myocytes
      treated by progesterone].
AB  - The level of cAMP in the rats uterus myocytes under the effect of active
      metabolites of nitrogen and oxygen (NO, NO2- and H2O2) was studied in the
      conditions of progesterone influence on myocytes. Suspension of cells was
      selected with the use of collagenase and soy-bean inhibitor of tripsine. The
      amount of cAMP was determined with the use of standard reagents producted by
      "Amersham", England. It is established that the basal level of cAMP in cells is
      10.4 +/- 0.7 pmol cAMP/mg protein. Incubation of myocytes with forskoline, 0.1
      mM, 10 min, resulted in its 3.4 times increase. It testifies to adenilatcyclase
      activity characteristic of the great majority of cell objects in the uterus
      myocytes. The level of cAMP in the suspension insignificantly decreases at the
      protracted affecting with myocytes 10 nM progesterone (1 hour). Donator of
      nitrogen oxide (0.1 mM sodium nitroprusside) in the presence of progesterone
      substantially promoted the level of cAMP in cells at the protracted action (17 +/
      3 pmol cAMP/mg protein). Nitrite-anion and hydrogen peroxide in concentration 10
      nM (low physiological concentration) did not have the above effect. The results
      obtained prove that exactly the long-term influence of nitrogen oxide, instead of
      progesterone, can provide the increase of cAMP level in the uterus myometrium.

PMID- 16568615
TI  - [Assessment of free radical formation process in rats with different audiogenic
      seizure susceptibility by means of biochemiluminiscent methods].
AB  - Complex investigation of free radical process intensity by means of spontaneous,
      Fe(2+)- and H2O2-induced, luminol dependent biochemiluminescent methods was
      performed. The increased formation of reactive oxygen species and no change of
      hydroperoxide levels were found in brain of rats with high seizure
      susceptibility.

PMID- 16568616
TI  - [Effect of exogenous specific lectin on lectin activity in the wheat seedlings
      and leaves].
AB  - The effect of presowing treatment of wheat seeds by exogenous wheat lectin on
      endogenous activity of lectin as well as on RNA content in vegetative organs of
      wheat was investigated. The variability of lectin activity in the seedling and
      leaves of wheat plants was obtained. Both endogenous activity of lectin and RNA
      amount increase under the effect of exogenous lectin. This effect was partially
      inhibited by the hapten of the wheat lectin. The possibility of induction of
      modifications in both endogenous lectin pool and functional activity of plant
      genome by exogenous lectin is under discussion.

PMID- 16568617
TI  - [Determining the parameters for receptor-ligand interaction by serial dilution
      method for the case when the ligand and receptor are in a pre-existing mixture].
AB  - New methods of determining the binding parameters for ligand-receptor interaction
      are considered. The considered approaches are based on the earlier suggested
      method of serial dilution and application of so-called coordinates of dilution.
      It was shown that the suggested methods allow to evaluate affinity constant and
      ligand concentration even for the case, when the receptor and corresponding
      ligand of unknown concentration are in a mixture and their separation from each
      other is impossible. In this connection the suggested methods are especially
      useful for studying the ligand-receptor interaction if the receptor is very
      liable and its purification from the ligand would cause drastic changes of its
      binding properties.

PMID- 16568618
TI  - A survey and description of projects that support and promote fathering in
      Canada: still work to do to reach fathers in their real-life settings.
AB  - This study aimed to identify the characteristics of current Canadian intervention
      programs designed to support father involvement. Sixty-one projects in the 10
      provinces constituted the sample. Results show that most of the projects operate
      on limited budgets. The activities they offer mostly target fathers themselves to
      the exclusion of key people in their social environment. The discussion
      underscores the strenghts and weaknesses of father support programs, and
      guidelines for future intervention in this area are proposed.

PMID- 16568619
TI  - Sheway's services for substance using pregnant and parenting women: evaluating
      the outcomes for infants.
AB  - Sheway is a single-access comprehensive street-front service to pregnant and
      parenting women with a history of alcohol and/or drug abuse that is located in
      one of Canada's poorest neighbourhoods, the Downtown Eastside of Vancouver. This
      investigation assesses the concurrent health and social problems clients report
      upon entry into the program, service utilization, and the impact of services on
      neonate and infant well-being. Data were collected through the review of files
      from the 9 1/2 years of the agency's service. Findings suggest that the clients'
      concurrent health and social problems have increased over the years of operation
      while indicators of infant health have either improved or maintained steady
      rates.

PMID- 16568621
TI  - Perceived need and help-seeking for mental health problems among Canadian
      provinces and territories.
AB  - Perceived need for mental health care, professional help-seeking, use of self
      help groups, and reasons for not seeking professional care for mental health
      problems were investigated in the Canadian Community Health Survey (N = 129,543).
      Regional differences were found for all variables. The greatest level of
      Perceived Need Without Seeking Help, Professional Help-Seeking, and Use of Self
      Help Groups were found in the Yukon/Northwest Territories/Nunavut. These findings
      likely reflect rural isolation and differences in socioeconomic levels associated
      with different regions in Canada. Regional differences indicate that efforts to
      improve the delivery of care need to be tailored to specific areas in Canada.

PMID- 16568620
TI  - [Experience in cross training within the context if integration of patient care
      team services in southeast Montreal].
AB  - Improved functioning in the mental health resource network can be guided by cross
      training procedures involving exchanges of clinical personnel. In 2003, Douglas
      Hospital along with the Centres locaux de services communautaires (CLSCs) and
      community organizations in southwest Montreal conducted a pilot project on
      training exchanges involving 14 clinical teams and 21 workers. Analysis of self
      administered questionnaires as well as content analysis of a focus group revealed
      a very high degree of satisfaction with the project. However, differences of
      opinion were noted regarding the content and orientation of the training and ways
      to ensure client confidentiality. The very strong demand for participation in the
      training courses offered, as well as the high level of satisfaction on the part
      of participants, testifies to the relevance of new series of personnel rotations.
      These rotations could be broadened so as to improve the continuity of services
      offered to people who have concomitant diagnoses of mental health and drug
      addiction problems.

PMID- 16568622
TI  - Mental health respite services: a grounded service delivery model.
AB  - A needs assessment for mental health respite services was undertaken at Waterloo
      Regional Homes for Mental Health in Kitchener, Ontario. Twenty-seven participants
      (consumers, carers, and service providers) were asked about their perceptions of
      the need for mental health respite services, and about their preferences for a
      model of respite in their community. A convergent analysis of participants'
      responses leads to one possible model of respite, while a divergent analysis
      considers program and value dilemmas for potential planners of programs directed
      at multiple stakeholders. Participants' frustrations with current services remind
      mental health programs of the importance of consulting with all stakeholders as
      they evaluate and develop programs.

PMID- 16568623
TI  - [Social representation of pregnancy in adolescence: appraisal of dominant
      attitudes and others of negative impact].
AB  - This study was undertaken to gather information on the social representations of
      teenage pregnancy among adolescents, aged between 15 and 17. Eighteen focus
      groups were conducted among 150 boys and girls. The data were subjected to a
      qualitative content analysis. Results show that youths did not form homogeneous
      groups. The points of view expressed gave rise to 4 dimensions (emotive,
      reflexive, psychobiological, economic-social) and 4 positions (negative,
      positive, ambivalent and dynamic). From these dimensions and positions, 4
      representations of teenage pregnancy were identified: pregnancy as a problem,
      pregnancy as a project, pregnancy as a source of tension, and pregnancy as a
      source of power. This study illustrates the importance of educative strategies
      such as going beyond alarmist preventive messages, opening dialogue with and
      between youngsters, and promoting social support and mutual aid.

PMID- 16568624
TI  - Experiences of harm reduction among women with alcohol use problems.
AB  - This paper explores women's choice of controlled drinking or abstinence goals in
      harm reduction treatment programs for alcohol use problems. Situated within
      debates about controlled or abstinence goals for alcohol use, this research
      project provides a specific focus on women's treatment needs. We explore evidence
      which reveals that women in treatment for alcohol problems often hold deeply
      internalized dominant social ideologies on addiction. Results demonstrate that
      while offered the choice of abstinence or controlled use goals, most women
      defined themselves as "addicts," adopted a disease metaphor of "addiction," and
      chose abstinence. The findings here raise questions about whether or not clients
      receive sufficient education about harm reduction and controlled drinking and
      make adequately informed choices.

PMID- 16568625
TI  - Promoting multidisciplinary relationships: a pragmatic framework for helping
      service providers to work collaboratively.
AB  - Multidisciplinary teamwork is increasingly considered the ideal way to provide
      mental health services. This is especially the case when working with children or
      families. However, there is little easy-to-use information available to help
      practicing professionals recognize and overcome barriers to working in
      multidisciplinary settings. There are even fewer resources intended for use
      across disiplines. This paper offers a practical approach to help mental health
      professionals identify barriers to teamwork and create solutions to those
      barriers.

PMID- 16568627
TI  - Vaccination, within-host dynamics, and virulence evolution.
AB  - We explore the potential consequences of vaccination on parasite epidemiology and
      evolution. Our model combines a microscopic (within-host dynamics) and a
      macroscopic (epidemiological dynamics) description of the interaction between the
      parasite and its host. This approach allows relevant epidemiological traits such
      as parasite transmission, parasite virulence, and host recovery to emerge from a
      mechanistic model of acute infection describing the interaction between the
      parasite and the host immune system. We model the effect of a vaccine as an
      activator of immunity enhancing the replication rate of lymphocytes, their
      initial density at infection's initiation, their efficacy to kill the parasite,
      or their activation delay after infection. We analyze the evolution of the
      replication rate of parasites and show that vaccination may promote the evolution
      of faster replicating and, consequently, more virulent strains. We also show that
      intermediate vaccination coverage may lead to the coexistence of two different
      parasite strategies (a low-virulence strain adapted to naive hosts, and a high
      virulence strain, more generalist, adapted to both naive and vaccinated hosts).
      We discuss the consequences of various vaccination strategies under different
      epidemiological situations using several distinct measures to evaluate the cost
      induced by the parasite on individuals and entire host populations.

PMID- 16568628
TI  - Parasite local adaptation in a geographic mosaic.
AB  - A central prediction of the geographic mosaic theory of coevolution is that
      coevolving interspecific interactions will show varying degrees of local
      maladaptation. According to the theory, much of this local maladaptation is
      driven by selection mosaics and spatially intermingled coevolutionary hot and
      cold spots, rather than a simple balance between gene flow and selection. Here I
      develop a genetic model of host-parasite coevolution that is sufficiently general
      to incorporate selection mosaics, coevolutionary hot and cold spots, and a
      diverse array of genetic systems of infection/resistance. Results from this model
      show that the selection mosaics experienced by the interacting species are an
      important determinant of the sign and magnitude of local maladaptation. In some
      cases, this effect may be stronger than a previously described effect of relative
      rates of parasite and host gene flow. These results provide the first theoretical
      evidence that selection mosaics and coevolutionary hot and cold spots per se
      determine the magnitude and sign of local maladaptation. At the same time,
      however, these results demonstrate that coevolution in a geographic mosaic can
      lead to virtually any pattern of local adaptation or local maladaptation.
      Consequently, empirical studies that describe only patterns of local adaptation
      or maladaptation do not provide evidence either for or against the theory.

PMID- 16568626
TI  - Differentiation among populations with migration, mutation, and drift:
      implications for genetic inference.
AB  - Populations may become differentiated from one another as a result of genetic
      drift. The amounts and patterns of differentiation at neutral loci are determined
      by local population sizes, migration rates among populations, and mutation rates.
      We provide exact analytical expressions for the mean, variance, and covariance of
      a stochastic model for hierarchically structured populations subject to
      migration, mutation, and drift. In addition to the expected correlation in allele
      frequencies among populations in the same geographic region, we demonstrate that
      there is a substantial correlation in allele frequencies among regions at the top
      level of the hierarchy. We propose a hierarchical Bayesian model for inference of
      Wright's F-statistics in a two-level hierarchy in which we estimate the among
      region correlation in allele frequencies by substituting replication across loci
      for replication across time. We illustrate the approach through an analysis of
      human microsatellite data, and we show that approaches ignoring the among-region
      correlation in allele frequencies underestimate the amount of genetic
      differentiation among major geographic population groups by approximately 30%.
      Finally, we discuss the implications of these results for the use and
      interpretation of F-statistics in evolutionary studies.

PMID- 16568629
TI  - Parasite-host specificity: experimental studies on the basis of parasite
      adaptation.
AB  - Specificity in parasitic interactions can be defined by host genotypes that are
      resistant to only a subset of parasite genotypes and parasite genotypes that are
      infective on a subset of host genotypes. It is not always clear if specificity is
      determined by the genotypes of the interactors, or if phenotypic plasticity
      (sometimes called acclimation) plays a larger role. Coevolutionary outcomes
      critically depend on the pervasiveness of genetic interactions. We studied
      specificity using the bacterial parasite Pasteuria ramosa and its crustacean host
      Daphnia magna. First, we tested for short-term adaptation of P. ramosa lines that
      had been rapidly shifted among different host genotypes. Adaptation at this time
      scale would demonstrate the contribution of phenotypic plasticity to specificity.
      We found that infectivity was stable across lines irrespective of recent passage
      history, indicating that in the short term infection outcomes are fixed by
      genetic backgrounds. Second, we studied longer-term evolution with two host
      clones and two parasite lines. In this experiment, P. ramosa lines had the
      possibility to evolve adaptations to the host genotype (clone) in which they were
      serially passaged, which allowed us to test for a genetic component to
      specificity. Substantial differences arose in the two passaged lines: one
      parasite line gained infectivity on the host clone it was grown on, but it lost
      infectivity on the other host genotype (this line evolved specificity), while the
      other parasite line evolved higher infectivity on both host clones. We crossed
      the two host genotypes used in the serial passage experiment and found evidence
      that the number of host genes that underlies resistance variation is small. In
      sum, our results show that P. ramosa specificity is a stably inherited trait, it
      can evolve rapidly, and it is controlled by few genes in the host. These findings
      are consistent with the idea of a rapid, ongoing arms race between the bacterium
      and its host.

PMID- 16568630
TI  - Evolutionary radiation of "stone plants" in the genus Argyroderma (Aizoaceae):
      unraveling the effects of landscape, habitat, and flowering time.
AB  - Recent phylogenetic evidence suggests that the extraordinary diversity of the
      Cape Floristic Kingdom in South Africa may be the result of widespread
      evolutionary radiation. Our understanding of the role of adaptive versus neutral
      processes in these radiations remains largely speculative. In this study we
      investigated factors involved in the diversification of Argyroderma, a genus
      within the most spectacular of the Cape radiations, that of the Ruschioid
      subfamily of the Aizoaceae. We used amplified fragment length polymorphisms and a
      suite of morphological traits to elucidate patterns of differentiation within and
      between species of Argyroderma across the range of the genus. We then used a
      matrix correlation approach to assess the influence of landscape structure,
      edaphic gradients, and flowering phenology on phenotypic and neutral genetic
      divergence in the system. We found evidence for strong spatial genetic isolation
      at all taxonomic levels. In addition, genetic differentiation occurs along a
      temporal axis, between sympatric species with divergent flowering times.
      Morphological differentiation, which previous studies suggest is adaptive, occurs
      along a habitat axis, between populations occupying different edaphic
      microenvironments. Morphological differentiation is in turn significantly
      associated with flowering time shifts. Thus we propose that diversification
      within Argyroderma has occurred through a process of adaptive speciation in
      allopatry. Spatially isolated populations diverge phenotypically in response to
      divergent habitat selection, which in turn leads to the evolution of reproductive
      isolation through divergence of flowering phenologies, perhaps as a correlated
      response to morphological divergence. Evidence suggests that diversification of
      the group has proceeded in two phases: the first involving divergence of
      allopatric taxa on varied microhabitats within a novel habitat type (the quartz
      gravel plains), and the second involving range expansion of an early flowering
      phenotype on the most extreme edaphic habitat and subsequent incomplete
      differentiation of allopatric populations of the early flowering group. These
      results point to adaptive speciation in allopatry as a likely model for the
      spectacular diversification of the ice-plant family in the dissected landscapes
      of the southern African winter rainfall deserts.

PMID- 16568631
TI  - Evolutionary responses of native plants to novel community members.
AB  - Both ecological and evolutionary processes can influence community assembly and
      stability, and native community members may respond both ecologically and
      evolutionarily as additional species enter established communities. Biological
      invasions provide a unique opportunity to examine these responses of native
      community members to novel species additions. Here, I use reciprocal transplant
      experiments among naturally invaded and uninvaded environments, along with
      experimental removals of exotic species, to determine whether exotic plant
      competitors and exotic insect herbivores evoke evolutionary changes in native
      plants. Specifically, I address whether the common native plant species Lotus
      wrangelianus has responded evolutionarily to a series of biological invasions by
      adapting to the presence of the exotic plant Medicago polymorpha and the exotic
      insect herbivore Hypera brunneipennis. Despite differences in selection regimes
      between invaded and uninvaded environments and the presence of genetic variation
      for traits relevant to the novel competitive and plant-herbivore interactions,
      these experiments failed to reveal evidence that Lotus has responded
      evolutionarily to the double invasion of Medicago followed by H. brunneipennis.
      However, when herbivory from H. brunneipennis was experimentally reduced, Lotus
      plants from source populations invaded by Medicago outperformed plants from
      uninvaded source populations when transplanted into heavily invaded destination
      environments. Therefore, Lotus showed evidence of adaptation to Medicago invasion
      but not to the newer invasion of an exotic shared herbivore. The presence of this
      exotic insect herbivore alters the outcome of evolutionary responses in this
      system and counteracts adaptation by the native Lotus to invasion by the exotic
      plant Medicago. This result has broad implications for the conservation of native
      communities. While native species may be able to adapt to the presence of one or
      a few exotics, a multitude of invasions may limit the ability of natives to
      respond evolutionarily to the novel and frequently changing selection pressures
      that arise with subsequent invasions.

PMID- 16568632
TI  - The fitness effects of outcrossing in Calylophus serrulatus, a permanent
      translocation heterozygote.
AB  - Small and relatively isolated populations that occupy fragmented habitat are at
      risk of local extinction. However, fitness consequences of fragmentation related
      to mating distance, such as inbreeding depression following increased self- and
      near-neighbor mating, may not follow standard expectations in species with
      specialized genetic systems. We investigated the effect of mating distance on
      progeny fitness in Calylophus serrulatus, a primarily autogamous, permanent
      translocation heterozygote that is restricted to prairie fragments in the North
      American tallgrass prairie region. We pollinated flowers by hand in the field
      with pollen sampled at various distances from the maternal parent within and
      between three populations in southeastern Minnesota. We raised the progeny in a
      greenhouse and measured fitness-related characters. Because their genetic system
      prevents loss of heterozygosity throughout much of the genome, regardless of
      inbreeding, permanent translocation heterozygotes are not expected to exhibit
      inbreeding depression. Consistent with this expectation, in no case did progeny
      of self matings suffer significantly reduced mean fitness compared to progeny
      from crosses between plants. Crosses between plants in the two closely situated
      (2 km) populations yielded progeny with fitness intermediate to their parents,
      but crosses between each of those populations and the more distant (20 km)
      population yielded progeny with reduced fitness, suggesting outbreeding
      depression at this largest spatial scale. Similarly, fitness of self-pollinated
      progeny and progeny from "near" crosses (<2 m) within populations tended to be
      higher than "mid" (10-25 m) and "far" (>35 m) cross-progeny fitness. Under the
      current conditions of fragmentation, it seems likely that the distant matings
      that produce outbreeding depression are rare. It appears that mean fitness in
      this species is maintained in the context of severe fragmentation of its
      populations, largely because of its genetic system.

PMID- 16568633
TI  - Inbreeding depression, increased phenotypic variance, and a trade-off between
      gonads and appendages in selfed progeny of the aphid Prociphilus oriens.
AB  - Trade-offs are potentially common among two or more traits whose development is
      dependent on the same resources. To detect genetic trade-offs, the techniques of
      quantitative genetics, pedigree analyses, and selection experiments have been
      used. This study demonstrates genetically based trade-offs between gonads and
      appendages in hatched larvae of the aphid Prociphilus oriens by focusing on
      enlarged variance among the families of selfed progeny. The selfed and outbred
      families were compared in respect to the size of morphological traits, gonad
      volume, and hatch dates as well as egg volume. Selfing not only increased the
      among-family variance component in all larval traits examined, but it also
      increased the mean size of all the morphological traits significantly. In
      contrast, gonad volume, a fitness component, was reduced with selfing.
      Calculation of the allometry (log-transformed regression) of larval traits to egg
      volume indicated that in the outbred group, morphological traits grew slowly
      relative to egg volume with slopes below 0.25, whereas gonads exhibited isometric
      growth. With selfing, most morphological traits had significantly steeper slopes,
      whereas the slope for gonads was greatly decreased. When the effect of egg volume
      was statistically removed from the means of selfed families, significant negative
      correlation was detected between the adjusted means of gonad volume and those of
      tibia length. This result suggests genetic trade-offs between gonad volume and
      tibia length. Thus, the evidence implies that at the loci governing the
      development of appendages, the dominant alleles function to canalize the
      development of tibiae into an optimal size, irrespective of egg volume. It is
      hypothesized that increased homozygosity of the deleterious recessive alleles
      reduced gonad volume through increasing the resource allocation to tibiae. The
      hypothesis of the gonad-appendage trade-off could be applied to explain the
      phenotypic evolution in some aphid species.

PMID- 16568634
TI  - Influence of antibiotic treatment and Wolbachia curing on sexual isolation among
      Drosophila melanogaster cage populations.
AB  - Speciation depends on the establishment of reproductive isolation between
      populations of the same species. Whether assortative mating evolves as a by
      product of adaptation is a major question relevant to the origin of species by
      reproductive isolation. The long-term selection populations used here were
      originally established 30 years ago from a single cage population (originating
      from a maternal one) and subsequently subjected to divergent selection for
      tolerance of toxins in food (heavy metals versus ethanol) to investigate this
      question. Those populations now differ in sexual isolation and Wolbachia
      infection status. Wolbachia are common and widespread bacteria infecting
      arthropods and nematodes. Attention has recently focused on their potential role
      in insect speciation, due to post-mating sperm-egg incompatibilities induced by
      the bacteria. In this paper we examine the potential effect of Wolbachia on the
      level of sexual isolation. By antibiotic curing, we show that removal of
      Wolbachia decreases levels of mate discrimination (sexual isolation index)
      between populations by about 50%. Backcrossing experiments confirm that this
      effect is due to infection status rather than to genetic changes in the
      populations resulting from antibiotic treatment. Antibiotic treatment has no
      effect on mate discrimination level between uninfected populations. Our findings
      suggest that the presence of Wolbachia (or another undetected bacterial
      associate) act as an additive factor contributing to the level of pre-mating
      isolation between these Drosophila melanogaster populations. Given the ubiquity
      of bacterial associates of insects, such effects could be relevant to some
      speciation events.

PMID- 16568635
TI  - Standing genetic variance for female resistance to harm from males and its
      relationship to intralocus sexual conflict.
AB  - Interlocus sexual conflict theory predicts that some male adaptations are harmful
      to their mates. Females are therefore expected to evolve resistance to this harm.
      Using cytogenetic cloning techniques, we tested for heritable genetic variation
      among females for resistance to harm from males and determined whether propensity
      to remate, female body size, and intralocus conflict contributes to this
      variation. We found low but significant heritability for female resistance, but
      this variation accounted for more than half of the standing genetic variation for
      net fitness among females. We found no association between female resistance and
      female body size or level of intralocus sexual conflict. Reluctance to remate was
      found to be an important factor contributing to the female resistance phenotype,
      and we found a positive selection gradient on this trait. However, we observed
      only a nonsignificant positive correlation between a female's resistance and her
      net fitness. One factor contributing to the observed nominal level of selection
      on female resistance was that males cause the greatest amount of harm to females
      with the highest intrinsic fecundity.

PMID- 16568636
TI  - The contrasting genetic architecture of wing size, viability, and development
      time in a rainforest species and its more widely distributed relative.
AB  - Divergence among populations can occur via additive genetic effects and/or
      because of epistatic interactions among genes. Here we use line-cross analysis to
      compare the importance of epistasis in divergence among two sympatric Drosophila
      species from eastern Australia, one (D. serrata) distributed continuously and the
      other (D. birchii) confined to rainforest habitats that are often disjunct. For
      D. serrata, crosses indicated that development time and wing size differences
      were due to additive genetic effects, while for viability there were digenic
      epistatic effects. Crosses comparing geographically close populations as well as
      those involving the most geographically distant populations (including the
      southern species border) revealed epistatic interactions, whereas crosses at an
      intermediate distance showed no epistasis. In D. birchii, there was no evidence
      of epistasis for viability, although for development time and wing size there was
      epistasis in the cross between the most geographically diverged populations.
      Strong epistasis has not developed among the D. birchii populations, and this
      habitat specialist does not show stronger epistasis than D. serrata. Given that
      epistasis has been detected in crosses with other species from eastern Australia,
      including the recently introduced D. melanogaster, the results point to epistasis
      not being directly linked to divergence times among populations.

PMID- 16568637
TI  - The adaptive significance of reptilian viviparity in the tropics: testing the
      maternal manipulation hypothesis.
AB  - Phylogenetic transitions from oviparity to viviparity in reptiles generally have
      occurred in cold climates, apparently driven by selective advantages accruing
      from maternal regulation of incubation temperature. But why, then, are viviparous
      reptiles so successful in tropical climates? Viviparity might enhance fitness in
      the tropics via the same pathway as in the temperate zone, if pregnant female
      reptiles in the tropics maintain more stable temperatures than are available in
      nests (Shine's maternal manipulation hypothesis). Alternatively, viviparity might
      succeed in the tropics for entirely different reasons than apply in the temperate
      zone. Our data support the maternal manipulation hypothesis. In a laboratory
      thermal gradient, pregnant death adders (Acanthophis praelongus) from tropical
      Australia maintained less variable body temperatures (but similar mean
      temperatures) than did nonpregnant females. Females kept at a diel range of 25-31
      degrees C (as selected by pregnant females) gave birth earlier and produced
      larger offspring (greater body length and head size) than did females kept at 23
      33 degrees C (as selected by nonpregnant snakes). Larger body size enhanced
      offspring recapture rates (presumably reflecting survival rates) in the field.
      Thus, even in the tropics, reproducing female reptiles manipulate the thermal
      regimes experienced by their developing embryos in ways that enhance the fitness
      of their offspring. This similarity across climatic zones suggests that a single
      general hypothesis--maternal manipulation of thermal conditions for embryogenesis
      -may explain the selective advantage of viviparity in tropical as well as cold
      climate reptiles.

PMID- 16568638
TI  - Why does a trait evolve multiple times within a clade? Repeated evolution of
      snakelike body form in squamate reptiles.
AB  - Why does a trait evolve repeatedly within a clade? When examining the evolution
      of a trait, evolutionary biologists typically focus on the selective advantages
      it may confer and the genetic and developmental mechanisms that allow it to vary.
      Although these factors may be necessary to explain why a trait evolves in a
      particular instance, they may not be sufficient to explain phylogenetic patterns
      of repeated evolution or conservatism. Instead, other factors may also be
      important, such as biogeography and competitive interactions. In squamate
      reptiles (lizards and snakes) a dramatic transition in body form has occurred
      repeatedly, from a fully limbed, lizardlike body form to a limb-reduced,
      elongate, snakelike body form. We analyze this trait in a phylogenetic and
      biogeographic context to address why this transition occurred so frequently. We
      included 261 species for which morphometric data and molecular phylogenetic
      information were available. Among the included species, snakelike body form has
      evolved about 25 times. Most lineages of snakelike squamates belong to one of two
      "ecomorphs," either short-tailed burrowers or long-tailed surface dwellers. The
      repeated origins of snakelike squamates appear to be associated with the in situ
      evolution of these two ecomorphs on different continental regions (including
      multiple origins of the burrowing morph within most continents), with very little
      dispersal of most limb-reduced lineages between continental regions. Overall, the
      number of repeated origins of snakelike morphology seems to depend on large-scale
      biogeographic patterns and community ecology, in addition to more traditional
      explanations (e.g., selection, development).

PMID- 16568639
TI  - Ecological and developmental context of natural selection: maternal effects and
      thermally induced plasticity in the frog Bombina orientalis.
AB  - Variation in fitness generated by differences in functional performance can often
      be traced to morphological variation among individuals within natural
      populations. However, morphological variation itself is strongly influenced by
      environmental factors (e.g., temperature) and maternal effects (e.g., variation
      in egg size). Understanding the full ecological context of individual variation
      and natural selection therefore requires an integrated view of how the
      interaction between the environment and development structures differences in
      morphology, performance, and fitness. Here we use naturally occurring
      environmental and maternal variation in the frog Bombina orientalis in South
      Korea to show that ovum size, average temperature, and variance in temperature
      during the early developmental period affect body sizes, shapes, locomotor
      performance, and ultimately the probability of an individual surviving
      interspecific predation in predictable but nonadditive ways. Specifically,
      environmental variability can significantly change the relationship between
      maternal investment in offspring and offspring fitness so that increased maternal
      investment can actually negatively affect offspring over a broad range of
      environments. Integrating environmental variation and developmental processes
      into traditional approaches of studying phenotypic variation and natural
      selection is likely to provide a more complete picture of the ecological context
      of evolutionary change.

PMID- 16568640
TI  - Persistence of egg recognition in the absence of cuckoo brood parasitism: pattern
      and mechanism.
AB  - Broad ecological shifts can render previously adaptive traits nonfunctional. It
      is an open question as to how and how quickly nonfunctional traits decay once the
      selective pressures that favored them are removed. The village weaverbird
      (Ploceus cucullatus) avoids brood parasitism by rejecting foreign eggs. African
      populations have evolved high levels of within-clutch uniformity as well as
      individual distinctiveness in egg color and spotting, a combination that
      facilitates identification of foreign eggs. In a companion study, I showed that
      these adaptations in egg appearance declined following introductions of weavers
      into habitats devoid of egg-mimicking brood parasites. Here, I use experimental
      parasitism in two ancestral and two introduced populations to test for changes in
      egg rejection behavior while controlling for changes in egg appearance.
      Introduced populations reject foreign eggs less frequently, but the ability of
      source and introduced populations to reject foreign eggs does not differ after
      controlling for the evolution of egg color and spotting. Therefore, egg rejection
      behavior in introduced populations of the village weaver has been compromised by
      changes in egg appearance, but there has been no significant decline in the
      birds' ability to recognize foreign eggs. This result reconciles earlier studies
      on this system and provides insights into the ways behavior can change over
      generations, especially in the context of recognition systems and the avoidance
      of brood parasitism.

PMID- 16568641
TI  - Morphological integration in the carnivoran skull.
AB  - The correlated evolution of traits may be a principal factor in morphological
      evolution, but it is typically studied in genetic or developmental systems. Most
      studies examining phenotypic trait correlations, through analysis of
      morphological integration, consider only few taxa, with limited ability to test
      hypotheses of the influence of trait integration on morphological variation and
      diversity. The few comparative studies in less inclusive groups have yielded
      varying relationships of integration to the key factors of phylogeny and diet. In
      this paper, I present analyses of cranial morphological integration in 30 species
      from the mammalian order Carnivora, spanning eight extant families and a wide
      range of ecological and morphological diversity. Fifty-five cranial landmarks
      were captured through three-dimensional digitization of 15-22 specimens for each
      species. Using a node-based phylogenetic distance matrix, a significant
      correlation was found between similarity in patterns of integration and
      phylogenetic relatedness within Felidae (cats) and Canidae (dogs), but not within
      more inclusive clades, when size-related variation was removed. When size was
      included, significant correlations were found across all Caniformia, Musteloidea,
      Mustelidae, and Felidae. There was a significant correlation between phylogeny
      and morphological integration only within the higher-level clade Feliformia
      (cats, civets, mongooses, and hyaenas) when a branch-length-based phylogenetic
      distance matrix was analyzed, with and without size. In contrast, diet was
      significantly correlated with similarity in morphological integration in arctoid
      carnivorans (bears, raccoons, and weasels), but had no significant relationship
      with integration in feliforms or canids. These results support the proposition
      that evolutionary history is correlated with cranial integration across large
      clades, although in some smaller clades diet also exerts significant influence on
      the correlated evolution of traits.

PMID- 16568642
TI  - Heterosis in an isolated, effectively small, and self-fertilizing population of
      the flowering plant Leavenworthia alabamica.
AB  - Mildly deleterious mutations are thought to play a major role in the extinction
      of natural populations, especially those that are small, isolated, or inbred.
      Self-fertilization should reduce the effective size of populations and
      simultaneously reduce migration between populations. A history of self
      fertilization should therefore cause a population to harbor a substantial "local
      drift load" caused by the fixation of mildly deleterious mutations. This
      hypothesis was tested in Leavenworthia alabamica, which contains large, self
      incompatible populations and smaller self-compatible populations with adaptations
      for self-fertilization. The fitness of offspring from within- and between
      population crosses was compared to quantify heterosis caused by the masking of
      deleterious alleles in the heterozygous state. Little heterosis was observed in
      crosses between five large, self-incompatible populations and two of the three
      small, self-fertilizing populations of L. alabamica. However, the most
      geographically isolated and genetically divergent self-fertilizing population
      (Tuscumbia) exhibited a 110.2% increase in germination and a 73.6% increase in
      fitness, which is consistent with a sizeable local drift load. The finding of
      substantial heterosis for fitness supports the idea that small effective size,
      reproductive isolation, and self-fertilization can make populations particularly
      vulnerable to mutation accumulation.

PMID- 16568643
TI  - Increased residual variance at developmental switch points: statistical artifact
      or indicator of exposed genotypic influence?
AB  - Discussing the organization of developmental switches, West-Eberhard (2003)
      proposed the use of regression residual plots to locate the neutral point of the
      switch, which is characterized by maximum genotypic influence on the resulting
      phenotype. However, statistical artifacts due to measurement error in nonlinear
      models might account for a substantial proportion of the increase of residuals
      variance at the switch point. Simulations based on field data show that increases
      in residual variance occur as artifacts when normal amounts of measurement error
      are present, even in absence of any genotypic variance. The results suggest that
      interpretation of nonlinear variation in thresold traits is problematic and
      requires considering this statistical effect. A method to estimate the weight of
      genotypic contribution to residual variance is proposed, and its assumptions and
      limitations are discussed.

PMID- 16568645
TI  - Equipment Troubleshooting.

PMID- 16568644
TI  - Latitudinal variation in sexual size dimorphism of sea-run masu salmon,
      Oncorhynchus masou.
AB  - Sexual size dimorphism (SSD), a difference in body size between the sexes, occurs
      in many animal species. Although the larger sex is often considered invariable
      within species, patterns of selection may result in interpopulation variation or
      even reversal of SSD. We evaluated correlations between latitude and female body
      size, male body size, and relative body size (male body size/female body size) in
      22 populations (ranging from 37 degrees N to 49 degrees N) of sea-run masu salmon
      (Oncorhynchus masou) that spawn in rivers along the Sea of Japan coast. Male size
      and the relative body size increased with latitude, but female size did not
      correlate with latitude. In addition, increase in male size with latitude was
      sufficient to result in a reversal of SSD, the switch-point being around 45
      degrees N. We suggest that the positive correlation between latitude and male
      size is due to increasing operational sex ratios or sexual selection on sea-run
      male body size that result from sex-biased patterns of anadromy. In conclusion,
      our study provides the first example of predictable geographic variation in SSD
      shaped by apparent patterns of sexual selection.

PMID- 16568646
TI  - Feeling sick? Consult a crystal ball.

PMID- 16568647
TI  - System takes a bite out of false alarms.

PMID- 16568648
TI  - Achieving a balanced fire protection plan.

PMID- 16568649
TI  - Confined space entry, part 1.

PMID- 16568650
TI  - Protecting workers against bioterrorism.

PMID- 16568651
TI  - Tortilla maker's safety a flat-out success.

PMID- 16568652
TI  - A harder sell.

PMID- 16568653
TI  - Next stop: convergence.

PMID- 16568654
TI  - A better guide to high-vis apparel.

PMID- 16568655
TI  - AC vs. solar power: choosing the right safety sign.

PMID- 16568656
TI  - [Studies on liquid fermentation of anamorph of Shiraia bambusicola].
AB  - A asexuae strain producing effective component hypocrellin was isolated from the
      hypha of Shiraia bambusicola sporo-carp. By liquid-state fermentation and
      orthogonal teat with shake flask culture, the optimum medium component and
      culture conditions were: saccharose 20 g/L, yeast extract 8 g/L, maize extract 2
      g/L, pH 6.0, culture broth quantity 50/250 mL(V/V) flask, inoculum 10% (V/V),
      culture temperature 28 degrees C, shake rotation 130 r/min, fermentation period
      96 h. The culture can produce 8 g Hypocrellin (E 1 cm (1%) 465 = 52) per liter
      fermentation broth. This study will provide basis for the future massively
      industrialized hypcorllin production.

PMID- 16568658
TI  - [Research on correlations of quality and growing environment of Smilax China].
AB  - OBJECTIVE: To establish a method to examine the contents of diosgenin of Smilax
      china L. in different fields ,and to evaluate the influence of the growing
      environment on its quality. METHODS: Kromasie C18 column was used. The mobile
      phase was CH3OH-H2O (94:6), flow rate: 1.0 ml/min,the detective wavelength was
      210 nm. RESULTS: Under the chromatographic condition the diosgenin can be
      completely separated,in the range of 5 microg-15 microg diosgenin had fine linear
      responses The mean recovery was 98.47%, and the RSD was 1.01%. CONCLUSIONS: The
      method was sensitive, simple and accurate. There were some correlations on the
      quality of Smilax china L. and growing environment.

PMID- 16568657
TI  - [Clustered shoot induction and rapid propagation on Pinellia ternate].
AB  - OBJECT: To establish the rapid propagation system of Pinellia ternate. METHOD:
      The Clustered shoots were induced by the explant lamina and petiole from the
      terminal bud of Pinellia ternate tuber in test tube. RESULT: The plantlets could
      regenerate from the lamina and petiole directly without via the callus. The MS
      Medium with 2.0 mg/L 6-BA and 0.1 mg/L NAA was optimal for the induction of
      culstered shoots from explants of lamina; the MS with 2.0 mg/L 6-BA and 0.25 mg/L
      NAA was best for the explants of petiole; and the 1/2 MS with 1.0 mg/L KT and 2.0
      mg/L NAA was the better medium for induction of roots. CONCLUSION: The
      regenerated rate of Pinellia ternata can improve by inducing the clustered shoots
      from the explants of lamina and petiole directly.

PMID- 16568659
TI  - [Studies on flavones in the leaves of Cyclocarya paliums (batal.) Iljinsk].
AB  - To do investigation of flavones from the leaves of Cyclocarya paliums (Batal.)
      Iljinsk. The pure products were isolated by column chromatography of silica gel,
      thin layer chromatography of silica gel and column chromatography of Sephadex LH
      20, their chemical structures were elucidated by NMR, IR and UV spectroscopic
      evidence. Four flavones were isolated from the leaves of Cyclocarya paliums. They
      are quercetin (I), kaempferol (II), kaempferol-7-O-alpha-L-rhamnopyranosyl (III)
      ,and kaempferol-4'-methoxyl-7-O-beta-D-mancopyranosyl (IV). Compounds III and IV
      are obtained for the first time from this plants.

PMID- 16568661
TI  - [Preparation of soybean isoflavone aglycones by reversed-phase high performance
      liquid chromatography from Semen Sojae Praeparatum].
AB  - OBJECTIVE: An efficient method for the isolation of isoflavone aglycones from
      Semen Sojae Praeparatum was developed. METHODS: The crude isoflavones were
      extracted by 75% aqueous ethanol and primarily purified by 1300 macroporous
      resin,and then the fractions containing daidzein, glycitein and genistein were
      obtained and subjected to preparative HPLC for the isolation of target
      components. RESULTS: Daidzein, glycitein and genistein were obtained with
      purities of over 99%, etermined by analytical HPLC. CONCLUSION: This technique is
      simple and suitable for the isolation of isoflavone aglycones from Semen Sojae
      Praeparatum.

PMID- 16568660
TI  - [Study on sterols and triterpenes from the stems of Akebia quinata].
AB  - The ethanol extract from Akebia quinata was seperated by dichloromethane, n
      butanol in sequence. Six compounds were isolated and identified as beta
      sitosterol (I), delta(5,22) stigmasterol (II), oleanolic acid (III), hederagenin
      (IV), daucosterol (V), delta(5,22) stigmasterol-3-O-beta-D-glycopyranoside (VI).
      Compound VI was isolated from Akebia plants for the first time.

PMID- 16568662
TI  - [Study of the relative recovery of sinomenine microdialysis system and it's
      influential factor].
AB  - OBJECTIVE: (1) To study the effect of concentration and flow rate on relative
      recovery (RR); (2) To study the difference Of relative recovery between probes;
      (3) To study the relationship between relative recovery and relative loss (RL).
      METHODS: HPLC. RESULTS: (1) The sinomenine concentration has no obvious effect on
      RR in the same flow rate. (2) RR is reduced by exponent law as the flow rate
      increases. (3) There is significent difference between probes. CONCLUSION: The RR
      isn't affected by sinomenine concentration as the flow rate is same. The flow
      rate has notable effect on RR as the sinomenine concentration is same. The RR of
      every probe should be assayed. We can take RL as RR to do in-vivo study.

PMID- 16568663
TI  - [Effect of Herba Epimedii Flavone on expression of OPG and RANKL in rat
      osteoblasts].
AB  - OBJECTIVE: To explore the effect of Herba Epimedii Flavone (HEF) on expression of
      OPG and RANKL in rat osteoblasts. METHODS: Osteoblasts were obtained from new
      born rat calvaria by digestive enzymes. The different HEF concentrations (0.1, 1,
      10, 100 ng/ml)were added into the culture medium. Total mRNA was prepared from
      osteoblasts after 48 h and 96 h, and mRNA expression of OPG and RANKL were
      detected by RT-PCR. RESULTS: The mRNA expression of OPG in osteoblasts
      significantly increased compared with that of the control group, and the
      V(OPF)/V(RANKL) ratio was deceased markedly in the treatment of 10 ng/ml group
      after 48 h. After 96 h, the mRNA expression of OPG significantly increased and
      the V(OPG)/V(RANKL) ratio was also decreased in the treatment group compared with
      that of the control group. CONCLUSION: HEF suppress the differentiation and
      maturate of osteoblast. Osteoporosis can be prevented and cured by HEF.

PMID- 16568664
TI  - [Study on the n-BuOH extract's fingerprint chromatography and bacteriostatic
      activity of Radix Isatis and correlation analysis].
AB  - The fingerprint chromatography and bacteriostatic activity of the n-BuOH extract
      of Radix Isatis were investigated. The chemical differemce in Radix Isatis from
      various sources was probed with system cluster analysis and it was co-researched
      with the bacteriostatic activity using correlation analysis in order to find the
      baterio static substances in Radix Isatis.

PMID- 16568665
TI  - [Study on the anti-cerebral ischemia/reperfusion injury effect and it's
      mechanisms of HD02].
AB  - OBJECTIVE: To study the effect of HD02 on Anti-Cerebral Ischemia/Reperfusion
      Injury. METHODS: The mice cerebral Ischemia/Reperfusion models were randomly
      divided into three group: control group, I/R group and treating groups (different
      dosages of HD02). At the end of the experiment, brain tissues were harvested to
      measure the brain water content, SOD activity, MDA content and the activity of
      Na+/K+ -ATP and Ca2+ -ATP enzyme. RESULTS: HD02 could obviously decrease the
      brain water content (P < 0.01) and the MDA content ( P < 0.01), while, it could
      also, increase the activity of SOD (P < 0.01) and the activity of ATP enzyme (P <
      0.05). These data showed that there was sever oxidative damage in brain tissue
      and HD02 could prevent I/R injury in brain.

PMID- 16568666
TI  - [Protective effects of the granule of Sambucus chinensis lindl on acute hepatic
      injury].
AB  - OBJECTIVE: To investigate the protective effects of the granule of Sambucus
      chinensis Lindl on acute hepatic injury. METHODS: The acute liver-injury model
      induced by CCl4 or D-GalN or ConA was established in mice or rats. RESULTS: The
      granule of Sambucus chinensis Lindl showed significantly protective effects on
      mice acute hepatic injury induced by CCl4 ,and the effects were concern of
      antagonizing lipoperoxidation and improving energy of Ca2+ -ATPase of theca
      mitochondria and microsome. It showed significantly protective effects on mice or
      rats acute hepatic injury induced by D-GalN or Con A, too. CONCLUSION: The
      granule of Sambucus chinensis Lindl showed significantly protective effects
      against many kinds of chemical and immunological liver injuries.

PMID- 16568668
TI  - [Technology of extraction of essential oil from leaves of Vitex negundo L. var.
      heterophylla (Franch.) Rehd. by supercritical CO2 apparatus].
AB  - By the designation of mono-factor experiments and orthogonal multifactor
      experiments, influences of extraction temperature, extraction pressure, CO2 flow
      rate and extraction times on the yield of oil from the leaves of Vitex negundo L.
      var. heterophylla (Franch.) Rehd. in the supercritical CO2 extraction process
      were investigated. The obtained optimal extraction technology was: the extraction
      pressure: 22 MPa; the extraction temperature: 45 degrees C; the CO2 flow rate: 25
      L/h and the extraction time: 3h. The oil yield on the above supercritical CO2
      extraction conditions was 3.22%.

PMID- 16568667
TI  - [Effect of taurochenodeoxycholic acid on immune function in mice].
AB  - OBJECTIVE: To observe the influence of Taurochenodeoxycholic Acid (TCDCA) on
      immun, function in mice. METHODS: T-Cell subgroups were determined by using Flow
      cytometry; The content of anti-body in serum was assayed by using
      Spectrophotometry; The phagocytosis of mononuclear phagocyte system was
      determined by using Carbon particle clearance test and anti-sheep blood cell
      hemolysin was determined by using Turbidimetric method. RESULTS: TCDCA
      signifeantly enhanced the percentage of CD and CD19+ lymphocytes and CD4+/CD8+
      value in peripheral blood and the content of serum hemolysin and lysozymem in
      mice. Moreover, TCDCA markedly improved the phagocytosis functions of mononuclear
      phagocyte system and observably inhibited delayed type hypersensitivity.
      CONCLUSION: TCDCA can significantly enhance the immune function in mice.

PMID- 16568669
TI  - [A technological study on the extraction of ultra-fine powder of Panax
      notoginsen].
AB  - OBJECTIVE: To investigate the extraction of ultra-fine powder Panax notoginsen.
      METHODS: The extraction rate of ginseng saponin Rg1, Re, Rb1, notoginseng saponin
      R1 and filtrated time were determined by alcoholic and aqueous extraction of
      Panax notoginsen in tablet, coarse powder, ultra-fine powder and recostitution
      granules of ultra-fine powder. RESULTS: The filtered time of ultra-fine powder of
      Panax notoginsen extraction and that of the tablet of Panax notoginsen extraction
      were similar, while the extraction rates of various saponins of it were high.
      CONCLUSION: The method of aqueous extrction in ltra-fine powder of Panax
      notoginsen is easy in filtrationer, higher in extraction rate of Panax notoginsen
      and lower in production cost.

PMID- 16568670
TI  - [Study on the optimal extraction process of polysaccharide from Baphicacanthus
      cuaia (Nees) Bremek with the uniform design].
AB  - OBJECTIVE: To study the optimal extraction process of polysaccharide from
      Baphicacanthus cuaia (Nees) Bremek. METHODS: The optimal extraction process was
      selected with uniform design and statistical analysis system (SAS). The content
      of polysaccharide in the extract was determined to investigate the influence of
      temperature of extraction, the time of extraction and the solid-liquid ratio on
      it. RESULTS: The optimal extraction process was extraction temperature 90 degrees
      C with 2 hours and with 1:50 (g/ml) of Baphicacanthus cuaia (Nees) Bremek weight
      to distilled water. The optimum extraction rates of Polysaccharide from
      Baphicacanthus cuaia (Nees) Bremek and Isatis indigotica Fort were 3.26% and
      12.76%.

PMID- 16568671
TI  - [Retrospective study of 53 erysipelas cases in Brazzaville University Hospital,
      Congo].
AB  - Hospitalizations for erysipelas became frequent in the Brazzaville (Congo)
      service of dermatology. A link between the use of topical corticosteroids for
      bleaching purpose and erysipelas cases of the leg in women users has been evoked.
      We carried out a retrospective survey over eleven months analysing 53 files of
      patients hospitalized for erysipelas, among which 48 cases (91%) concerned
      topical corticosteroids users and 5 cases of (9%) non users. The average age of
      these patients was 26 years old, with extremes 18 and 55, for an hospitalization
      varying between 3 weeks and one month.

PMID- 16568672
TI  - [Contribution of ultrasound in the diagnosis of the complications of
      intramuscular injection in children].
AB  - During a prospective study conducted at the rehabilitation Center of the
      physically handicapped persons and at the mother-child Hospital in Bamako, the
      authors report 50 cases of neuromuscular complications of the quinine
      intramuscular injection in the child. The scan revealed muscular calcifications
      in 37 cases (740%), abscesses, in 7 cases (14%) and muscular inflammations in 6
      cases (12%). Xray of the affected limb was not systematic: it has been performed
      in four children in the case of a subjacent bone involment. It showed
      calcifications in two cases. If muscular abscess is easily diagnosed by clinical
      exam it is not the case for calcifications. The scan allows to set up a precise
      mapping of the muscular lesions, to determine their type and size. It also helps
      the clinicians in their therapeutic attitude. Medical treatment associated with
      rehabilitation has been carried out in 40 patients (80%) and surgery in 10
      patients (20%).

PMID- 16568673
TI  - [Biochemical profile of Buruli ulcer in Cote-d'Ivoire].
AB  - Our survey concerned seventy seven (77) patients suffering from Buruli ulcer and
      who have been classified according to two clinical situations: native ulcer,
      cleaned and clean ulcer The biochemical survey including about thirteen (13)
      parameters mainly conducted in clinic didn't show meaningful disturbance, apart
      from the CRP that proved to be positive in patients carrier of a native ulcer.

PMID- 16568674
TI  - [The subcutaneous etonogestrel implant: a new contraceptive method in Mayotte?].
AB  - The isle of Mayotte is a part of the Comoros archipelago, its political status is
      that of a French Territory Despite a birth control programme helping to space out
      the births rather than restricting their number, the Mayotte population growth is
      soaring. Since the visit of the President in May 2001 the subcutaneous
      etonogestrel implant became available for the population of Mayotte. We then
      carried out a study to evaluate the response given by 50 post-partum women to
      this new contraceptive method. 38% of the women declared to be willing to use
      this contraceptive device while 52% instead didn't wish to try. Although not
      clearly expressed, the wish to have large families is still there and can be
      explained by religious and cultural factors. Considering the study results, this
      contraceptive method could certainly be useful in Mayotte. However a well
      balanced education campaign, neither too negative nor too enthusiastic, should be
      necessary to avoid false expectations which in that case could induce widespread
      negative rumour towards the birth control method.

PMID- 16568675
TI  - [Aetiologies of pleural effusions in HIV-infected patients in Abidjan, Cote
      d'Ivoire].
AB  - From December 1995 to March 1996 a cross sectional study was carried out in the
      pulmonary Medicine Unit of Treichville in Abidjan. In order to specify the main
      aetiologies of pleural effusion, an investigation was conducted among 35 adult
      patients (19 men and 16 women) suffering from pleuritis. Overall, the mean age
      was 32.2 years (range: 19-53 years). All the patients underwent a standard chest
      x-ray a skin test with 10 units of tuberculin, a whole blood cells count with CD4
      T cells count and HIV test. The following analysis were performed on the pleural
      fluid for all patients: cytological, bacteriological and mycobacteriological
      examination. Some patients underwent as well a pleural biopsy performed by
      Abram's needle. Pleural fluid was clear in 24 cases (69%). Empyema was found in 8
      cases (23%) and hemorrhagic fluid in 3 cases (9%). Tuberculosis was the dominant
      aetiology of pleuritis noted in 29 patients (83%), followed by far by non
      tuberculous bacterial infections in 6 patients (17%). Tuberculosis associated
      with common bacterial infections was noted in 3 cases.

PMID- 16568676
TI  - [Systematic serologic detection of treponema at the antivenereal centre of the
      National Institute of Public Health in Abidjan (Cote-d'Ivoire), from 1994 to
      1999].
AB  - We conducted a medical records review on 11,662 patients consulting the
      antivenereal clinic of Treichville from 1994 to 1999. The main objective of the
      study was to analyse the data from systematic screening of syphilis in this
      specialized centre for sexual transmitted infection. The results of this study
      were: 162 (1.39%) patients had active syphilis; we noticed a decreasing incidence
      of syphilis during the last six years, 98.77% of the patients had symptoms of
      sexual transmitted diseases that did not directly evoke syphilis. In summary we
      can say that syphilis remains an important problem in the sexually transmitted
      infections consultation. The screening of syphilis must continue and needs to be
      extended to other services, because of the high frequency of asymptomatic forms
      and the existence of severe complications.

PMID- 16568677
TI  - [Prevalence of the HIV infection and five other sexually-transmitted infections
      among sex workers in Niamey, Niger].
AB  - We performed a systematic screening of HIV infection and five other sexually
      transmitted infections on a consecutive sample of 529 female sex workers from
      Niamey. HIV seroprevalence rate was 30.1%, with HIV-1 profile in 93.1% of the
      cases. For curable STI, 4.7% of women had treponematosis, 7% gonorrhoea, 16.8%
      Gardnerella vaginalis, 36.9% Mycoplasma hominis and 68.2% Chlamydia trachomatis
      infection. The percentage of women with at least one STI was significantly higher
      in HIV positive's: 95.6% against 87.9%. Only 7.9% of women were free of any
      infection.

PMID- 16568678
TI  - [Difficulties of the patients to undergo their ARV treatment at the Libreville
      outpatient health center, Gabon].
AB  - The therapeutic observance is a real issue of chronic diseases. This issue is
      twice as much important in the case of aids treatment by antiretrovirals as a
      good observance is essential to avoid emergence of resistances and to improve
      patients' health. A research was conducted in Libreville, the capital of Gabon,
      at the ambulatory treatment center of HIV patients. The interviews of one hundred
      patients of the center, under treatment for more than two months, concerned their
      problems related to specific drugs intake and have helped to point out some
      reasons of non observance. The first reason refers to side effects inducing many
      difficulties in regular drugs intakes, a complete information is requested by the
      patients. Another main reason of non observance or bad observance is linked to
      material and financial problems or to treatment's reduced accessibility The
      research points out the importance of supplementary treatment costs
      (transportation, sick leave, food). At last, major observations were made on
      schedule management, drugs intake management, needs for more information and help
      for prevention, everyday life and diet.

PMID- 16568679
TI  - [Epidemiological profile of the schistosomiasis in school children in the Agneby
      Region (south-east of Cote-d'Ivoire)].
AB  - A parasitological survey was conducted in the Agneby region (south-east Cote
      d'Ivoire) from November 2000 to February 2001 in order to establish the
      epidemiological profile of schistosomiasis in school children in this region.
      Stools and urines of 724 school children were examined. Faeces were examined by
      direct analysis completed by Kato and Ritchie methods. Analysis of urine samples
      was made through the technique of centrifugation (2.000 g for 10 minutes). This
      survey revealed the importance of schistosomiasis. 20.6% of the subjects were
      found carriers of Schistosoma mansoni eggs, 12.6% carriers of Schistosoma
      haematobium eggs and 3.2% were found carriers of eggs of two Schistosoma species.
      Prevalence was higher in Adzope than in Agboville and Schistosoma mansoni was
      globally prevalent. Males were significantly more infected than females and older
      children were more infected than young children. The prevalence distribution
      among people could be explained by behaviour and occupations.

PMID- 16568680
TI  - [Tinea capitis in department of dermatology and venerology in the University
      hospital of Donka at Conakry, Guinea].
AB  - The authors report the results of a study carried out on tinea capitis, in the
      Department of Dermatology and Venerology at the University Hospital of Donka in
      Conakry, during one year In this department, the tinea capitis represents 3.2% of
      the consultations and remains the second mycosis. Out of 414 consulted children,
      a male predominance of 75% was noted especially regarding the Trichophytic tinea.
      School children aged of 6-14 years old are the most affected by the disease. The
      trichophytic tinea is widely spread with 65.5% more than the microsporic 17% and
      inflammatory tinea 16.5%. The mixed tinea is exceptional and no case of favus has
      been found. The Trichophyton violaceum is the most dermatophyte to be found
      56.70% whereas a survey carried out in 1959 showed the predominance of T.
      soudanense and M. audouini. The Microsporum canis and an association of M. canis
      and T. violaceum are also to be found.

PMID- 16568681
TI  - [Fighting against Buruli ulcer: the Cote-d'Ivoire experience].
AB  - Caused by Mycobacterium ulcerans, Buruli ulcer is an infectious disease which
      leads to large cutaneous ulceration and is responsible for huge socio-economic
      consequences. Since 1997 the World Health Organization has started a global
      Buruli ulcer initiative in which African endemic countries are committed. After
      an epidemiological background of the disease in Cote-d'Ivoire and a description
      of the different clinical aspects, we report the main disease management actions
      carried out in the country by the National Program for Buruli ulcer control from
      1998 to 2003. It seems that surgical team missions carried out in health center
      to treat cases, early detection and treatment of cases together with the
      implementation of a specific poly-chemotherapy lead to an effective control of
      the disease.

PMID- 16568682
TI  - [Prevalence of tuberculous meningitis in Niamey's Hospital, Niger].
AB  - Tuberculosis is hyperendemic in Niger. In Niamey between June 2002 and May 2004,
      996 cerebro-spinal fluids (CSF) collected from meningitis suspected patients have
      been analysed by PCR for the detection of Neisseria meningitidis, Haemophilus
      influenzae and Streptococcus pneumoniae: the aetiologic diagnosis was obtained
      for 208 cases (20.9%). The Mycobacterium tuberculosis PCR assay performed on the
      negative samples was positive for 4 CSF: 0.4% prevalence among suspected cases of
      meningitis or 1.9% among confirmed bacterial meningitis.

PMID- 16568683
TI  - [Use of antiretroviral drugs invoices for the follow-up of a treatment programme.
      Example in Abidjan, Cote d'Ivoire].
AB  - A retrospective analysis of the prescriptions of the ARV treatment programme in
      Abidjan, Cote-d'Ivoire enabled the authors to assess the collected anonymous
      information in order to evaluate the efficacy of the programme. This collection
      of information helps to supervise each center at a lower cost, to alert on some
      working problems and to follow the quality of the observance. This supervision is
      possible regardless of the health care places, it can be carried out
      systematically from the administrative or financial services. In this study this
      follow-up reveals some problems.

PMID- 16568685
TI  - [Behaviour and HIV seroprevalence investigation in sex workers of Dirkou, Niger,
      2002].
AB  - In the framework of the Human Immunodeficiency Virus (HIV) surveillance,
      seroprevalence and behavioural survey was conducted in 2002 in Dirkou, a place of
      concentration of female sex workers (FSW) in Niger The global HIV seroprevalence
      found was 50% (CI at 95%: 40.6-59.36%). The behavioural survey revealed that 98%
      of FSW had heard about HIV whereas 78.7% know at least one HIV transmission way
      and 76.9% know at least one HIV prevention means. Only 33.3% declared using
      condom, what show that sensitisation efforts are needed to induce a behaviour
      change in FSW and their clients.

PMID- 16568686
TI  - [Palaeoparasitological study of atypical elements of the low and High Nile
      Valley].
AB  - Paleoparasitology in the Old World has mainly concerned the study of latrine
      sediments and coprolites collected from mummified bodies or archaeological
      strata, mostly preserved by natural conditions. For the first time, different
      unusual archaeological samples were studied to look for the eggs of helminths
      parasites (embalming reject jar, canopic package, shroud). Now, samples of
      organic matter have been successfully processed in order to extract helminths
      eggs, following the protocol of BOUCHET 2001 (4). Helminth eggs are frequently
      preserved in the late Quaternary archaeological contexts because of their hard
      wearing chitin shell. Six types of eggs were revealed (Schistosoma mansoni,
      Schistosoma haematobium, Taenia, Enterobius vermicularis, Ascaris lumbricoides
      and Trichuris trichiura). This study allows to enlarge the Palaeoparasitological
      research with material never exploited. Moreover, if we take into account
      identified parasite and geography, it's possible to enlarge the debate to
      parasite spatio-temporal migration. Considering the particular context of samples
      preservation, it's interesting to observe an exceptional conservation of
      parasitological sign related to excellent taphonomic condition (aridity anaeroby,
      rapid interruption of thanatomorphosis, natural "mummification").

PMID- 16568684
TI  - Evaluation of deltamethrin-impregnated bed nets and curtains for control of
      zoonotic cutaneous leishmaniasis in a hyperendemic area of Iran.
AB  - In the study carried out in the rural district of Borkhar (Isfahan, Iran) from
      March 2003 to March 2004 efficacy of deltamethrin impregnated bed nets (IBs) and
      curtains (ICs), polyester mesh size 156 holes/ inch2, (25 holes/cm2) were
      compared to that of non-impregnated bed nets (NIBs) and curtains (NICs), in
      relation to zoonotic cutaneous leishmaniasis (ZCL) control. Deltamethrin
      impregnated bed nets and curtains at 25 mg a.i./m2 were distributed among 168
      households in one of the villages and NIBs plus NICs among the same number of
      households in another village. In the third village similar numbers of households
      were used as control. Health education messages were disseminated to ensure the
      population's compliance with the proper use of bed nets and curtains in the two
      intervention areas. Entomological surveys using sticky paper traps were carried
      out in ten households in each village for the collection of sand flies from
      indoors and outdoors, every two weeks to assess the impact of insecticide
      impregnated bed nets and curtains on the density of Phlebotomus papatasi.
      Deltamethrin susceptibility tests and also bioassay tests were carried out on
      this species by WHO standard method. Case findings were done by house-to-house
      visits once a season and all the inhabitants of the selected households in each
      village were examined. The results showed that IBs and ICs can provide a definite
      personal protection against sand fly bites and interrupted the transmission of
      ZCL in the intervention village. NIBs and NICs did not provide any protection
      against the disease. There was no significant difference in monthly density of P.
      papatasi in indoors and outdoors among the villages (P > 0.05). Susceptibility
      tests showed that this species was susceptible to deltamethrin in the field
      population in the area. Bioassays confirmed that the treated nets with
      deltamethrin remain effective for more than three months and was an excellent
      mean of individual protection. It is recommended that IBs and ICs can be used
      widely in the control of ZCL in other similar foci such as hyperendemic and
      mesoendemic areas of Iran.

PMID- 16568687
TI  - [Urological works and biography of Dr. Felipe Alcala Santaella Nunez (1927-1977).
      Historical documentary analysis].
AB  - OBJECTIVES: In the middle of the 20th century, Urology in Valencia was fully
      consolidated as a surgical speciality since Prof. Molla started it about the end
      of the 19th century; Dr. Felipe Alcala Santaella Nunez stands out as the chairman
      of the Department of Urology of the "Hospital Provincial de Valencia", after his
      father Dr. Rafael Alcala Santaella. He achieved to form a group of renowned
      professionals, some of which still are in active practice. METHODS: We reviewed
      all his scientific work and the journals it was published in, mainly Archivos
      Espaioles de Urologia, through the Department of Medical History of the
      University of Valencia. His biography was reconstructed using the "Biographic and
      Bibliographic History of Spanish Urology" by Drs. E. Maganto Pavon and M. Perez
      Albacete, as well as direct interviews with family members. DISCUSSION: We
      emphasize the magnificent approach to the clinical presentations of tuberculosis
      he does in his doctoral thesis, analyzing its types by location, main features,
      and most adequate treatment. He also emphasized the importance of relapse in
      lithiasic patients and recommendations to be follow, as well as the condition of
      bladder neoplasias. CONCLUSIONS: We consider Dr. Felipe Alcala Santaella Nunez as
      a wide-experience-professional who mode solid contributions to the regional
      urology in his times, thanks to his excellent surgical abilities and dedication.

PMID- 16568688
TI  - [Congenital urological anomalies: epidemiological description and associated risk
      factors in Colombia 2001-2004].
AB  - OBJECTIVE: To determine the incidence of congenital anomalies of the urinary
      tract in Colombia and study their association with maternal risk factors.
      METHODS: We performed a register based, case control study using the data from
      the ECLAMC (Colaborative latinoamerican Study for Congenital Malformations) in
      Colombia, between June, 2001 and December, 2004. Positive Registries for any
      urological anomaly were selected. Calculations for the incidence of each
      abnormality were done. Odds ratio were estimated for 11 maternal variables.
      RESULTS: 83 positive registries were found. The established incidence was 0.43%.
      These anomalies accounted for 9.4% of the total of malformations. The obtained
      rate (x 10,000 births) for each anomaly was: hypospadias 17.7; chryptorchidism
      13.3; hydronephrosis 2.6; cystic renal disease 2.6; undeterminate sex 2.6;
      unilateral renal agenesis 1.3; micropenis 1.9; bilateral renal agenesis 0.7;
      patent urachus 0.3. The risk for renal defects increased with preterm birth, odds
      ratio OR= 3.66; 95% IC [1.13 - 13.82] and maternal chronic disease OR = 6, 18;
      95% CI [1.09 - 34.98]. A deterministic association was found with consanguinity
      between the parents. The positive associations for genital defects were: low
      birth weight OR = 4.07; 95% CI [2.00 - 8.25], preterm birth OR= 3.80; 95% CI
      [1.87 - 7.72], presence of malformated individuals in the family OR = 2.30; 95%
      CI [1.02 - 5.25], and smoking during pregnancy OR = 5.36; CI [1.01 - 28.51]. A
      deterministic association was found with alcohol ingestion during pregnancy.
      CONCLUSIONS: The prevalence of anomalies of the urinary tract in Colombia is
      considerably lower in comparison with European and North American statistics. The
      birth weight is the most important risk factor for anomalies like hypospadias and
      chriptorchidism. Consanguinity between the parents and alcohol ingestion during
      the pregnancy are determinant on the risk for renal and genital anomalies,
      respectively. Variables like smoking during pregnancy and chronic maternal
      disease must be deeply explored in the future to determine their role in the
      etiology of these defects.

PMID- 16568689
TI  - [Diagnostic yield of the extended prostatic biopsy with 10 cores. Prospective
      study on 222 patients].
AB  - OBJECTIVES: The number of biopsy samples for a proper prostate cancer diagnosis
      has not yet been established. We report our experience with the 10-sample
      extended biopsy. METHODS: We collected the results of a group of 222 patients
      undergoing extended ultrasound guided prostate biopsy with 10 samples. In
      addition to the sextant biopsies 2 extra samples were obtained from the dorsal
      apex area on each lobe. Results of this group were compared with a control group
      of 552 patients undergoing sextant biopsy in 2002 with the same inclusion in
      criteria. RESULTS: 60 patients had cancer (27.15%). The extra samples gave the
      diagnosis in 5 out of 60 patients, 8.33% of the tumors and 2.25% of all patients.
      Control group showed cancer in 24.5%, not having the difference statistical
      significance. The incidence in prostates smaller than 20 cc was 69.2%, 11.6% in
      prostates bigger than 50 cc. 80% of the patients with prostate cancer only in the
      extra samples have a volume smaller than 35 cc. Multivariate logistic regression
      study for the probability of prostate cancer only showed association with serum
      PSA and prostate volume but not with the number of samples. CONCLUSIONS: The
      extended biopsy is not indicated as an initial diagnostic technique, being
      reserved for specific cases such as repeated biopsies in patients with high risk
      pathology reports. Neither it is indicated in the bigger volume prostates.

PMID- 16568690
TI  - [The influence of "differentiated trandurethral resection" in the recurrence and
      progression of superficial bladder cancer].
AB  - OBJECTIVES: Experimental data show the relationship between the area of injured
      urothelium and recurrence rates in superficial bladder cancer. Tumor cell
      adherence is increased by the exposure to the extracellular matrix (ECM).
      Transurethral resection uncovers the ECM and might lead to recurrent tumors. The
      question if recurrences are increased by enlarged urothelium resection areas is
      difficult to answer because there will be no prospective studies available. We
      investigated if deeper and larger urothelial injuries, which are caused by
      differentiated resections lead to higher recurrence and progression rates than
      regular resections of bladder tumors. METHODS: 163 patients with superficial
      bladder cancer were retrospectively evaluated. Sixty-six received a
      differentiated resection and 97 a regular one. We analyzed the recurrence and
      progression rates over a minimum of 48 months as well as tumor persistence in the
      second resection. RESULTS: Patients with differentiated resections of bladder
      tumors were found to have no higher incidence of tumor recurrence and progression
      but showed a significantly higher percentage of tumor free second resections.
      CONCLUSIONS: As a model of enlarged urothelial lesions the differentiated
      resection technique for superficial bladder cancer has no negative influence on
      recurrence or progression rates. It seems unlikely that the extracellular matrix
      uncovered by resection is the main reason for the high recurrence rates. The
      significantly lower incidence of tumor persistence in the second resection favors
      the differentiated resection technique in the transurethral treatment.

PMID- 16568691
TI  - [Prevalence of incidental prostatic adenocarcinoma after suprapubic adenomectomy
      with or without previous prostatic biopsy].
AB  - OBJECTIVES: To establish the prevalence of incidental prostate cancer after
      transrectal ultrasound guided prostatic biopsy and subsequent suprapubic
      prostatic adenomectomy and to compare it with a similar group of patients who did
      not underwent biopsy before surgery. To evaluate treatment, outcomes, and disease
      progression in patients with incidental prostate cancer. METHODS: Retrospective
      study of 549 suprapubic adenomectomy performed between 1996-2001 (6 yr.),
      comparing the group of patients with biopsies before surgery vs. the group of
      patients without biopsies. RESULTS: 291 (53%) patients did not undergo biopsy
      before adenomectomy. 258 (47%) underwent biopsies. 25 incidental prostate cancers
      were detected, 19 (76%) in the group of no biopsy and 6 (24%) in the biopsy
      group. 88% pT1a and 12%pT1b. Mean Gleason score 4.5 (3-7). 84% of the patients
      did not receive treatment (21) ("wait and see"); 8% (2) androgen blockade; 8% (2)
      finasteride (2). Three patients (12%) in the group of no biopsy had disease
      progression. Mean follow-up was 48.1 months (22-96). No case of cancer-specific
      mortality was detected. CONCLUSIONS: Global prevalence of incidental prostate
      cancer in our series of patients undergoing suprapubic prostatic adenomectomy was
      4.55%. Prevalence was higher in the group of patients without previous biopsy
      (3.46%) than in the biopsy group (1.09%). Tumor progression was 12% and cancer
      specific survival 100% after a mean follow-up of 48.1 months (22-92). Previous
      prostatic biopsy in patients with suspicions digital rectal examination or
      elevated PSA diminishes the prevalence of incidental prostate cancer. Watchful
      waiting may be a valid option in some cases.

PMID- 16568692
TI  - [Allogeneic transplantation of peripheral blood hematopoietic stem-cells with low
      intensity conditioning for the treatment of a metastatic clear cell carcinoma.
      Preliminary results after two years of follow-up].
AB  - OBJECTIVES: To evaluate the toxicity and outcomes of the allogeneic
      transplantation of peripheral blood hematopoietic stem-cells with low intensity
      conditioning (mini-alo Bone Marrow transplantation-BMT) in metastatic renal cell
      carcinoma refractory to at least one line of systemic treatment. METHODS: From 30
      patients submitted to the Sant Pau's Hospital for immunotherapy between 1/2001
      and 1/2003, six patients finally underwent mini-alo BMT within a clinical trial.
      Conditioning: Fludarabine: 30 minute i.v. infusion of 13 mg/m2 on days -9, -8, 
      7, -6 and -5. Busulfan: 1 mg/kg (real weight) q 6 hours, PO on days -6, -5, and 
      4 (4 doses per day on days -6 and -5, and 2 doses only on day -4, total number of
      doses 10). RESULTS: Two patients achieved partial response, one patient
      stabilized disease, and two patients had progression on days +30 and +60.
      Therefore, 2/3 patients surviving more than six months achieved partial response.
      One patient died on day +30 after acute hepatic graft-versus-host disease.
      Complete chimerism was demonstrated in all patients. CONCLUSIONS: The mimni-alo
      BMT is feasible in patients with metastatic renal cell carcinoma and provides
      objective responses, although its efficacy should be confirmed by phase III
      clinical trials.

PMID- 16568694
TI  - [Cystic ectasia of the rete testis].
AB  - OBJECTIVES: The cystic ectasia of the rete testis is a benign entity with a
      typical ultrasound appearance as a collection of small hypoechoic structures in
      the confluence of the mediastinum testis. The clinical importance of these entity
      remains on doing an adequate differential diagnosis with testicular neoplasias
      with a cystic component. METHODS: We retrospectively reviewed the database of the
      Ultrasound Unit in the Department of Urology looking for patients with a
      diagnosis of cystic ectasia of the rete testis over a six-year period. RESULTS:
      Three cases of cystic ectasia of the rete testis were diagnosed over the six-year
      period, in all the indication for ultrasound was testicular pain. Mean patient
      age was 62 years. No patient developed testicular tumor on follow-up.
      CONCLUSIONS: The knowledge of the ultrasound characteristics found in the cystic
      ectasia of the rete testis helps to make a proper diagnosis of this benign entity
      without the need of indication of testicular biopsy.

PMID- 16568693
TI  - [Laparoscopic retroperitoneal adrenalectomy as a minimally invasive option for
      the treatment of adrenal tumors].
AB  - OBJECTIVES: The excision of the adrenal gland by laparoscopic approach is the
      gold standard for the treatment of adrenal tumors smaller than 6 cm. Most
      Brazilian centres favour the transperitoneal approach. The objective of the
      present prospective study was to show the intraoperative and postoperative
      results of patients undergoing adrenal laparoscopic surgery through a lateral
      retroperitoneal approach performed by an individual surgeon. METHODS: Between
      January 2000 and October 2004, 35 patients (16 males and 19 females) with adrenal
      lesions, including 4 Cushing's syndrome, 4 Conn's syndrome, 1 neuroganglioma, 4
      pheochromocytoma, 17 nonfunctioning adenomas, 1 virilizing tumor, and 4 cases of
      adrenal nodule after treatment of a non-adrenal primary neoplasia, prospectively
      underwent retroperitoneoscopic adenomectomy by one surgeon. We describe surgical
      times, estimated blood losses, time to oral intake, analgesic requirements,
      surgical complications and conversion rates, hospital stay and time to return to
      usual activities, comparing our results with other series in the literature.
      RESULTS: All procedures were successfully completed. Mean surgical time was 135
      minutes, mean estimated blood loss 235 ml, mean time to oral intake 12 hours, no
      patient required analgesics after the second postoperative day, mean hospital
      stay was 2 days, and mean time to return to usual life activities 3 weeks. There
      were two complications, one case of intraoperative hypercapnia and one case with
      postoperative pneumonia. Conversion to open surgery was not required in any case.
      CONCLUSIONS: Retroperitoneoscopic adrenalectomy may be performed effectively and
      safely, with a low complication rate, independently of the etiology of the
      lesion. The lateral retroperitoneoscopic access is an excellent option for the
      minimally invasive treatment of the adrenal glands.

PMID- 16568695
TI  - [Indications, morbidity and mortality of the open nephrectomy. Analyses of 681
      cases and bibliographic review].
AB  - OBJECTIVES: To have data about the indications, morbidity and mortality of the
      nephrectomy by the open approach, to obtain information that could be compared
      with the laparoscopic approach. To our knowledge there is not a similar review in
      the Spanish literature since the 60's. METHODS: We analyzed 681 nephrectomies
      accounting for a 5.7% of a total of 11.845 operative reports registered in our
      centre over the last 25 years. For outcome analysis, 93 cadaver donor
      nephrectomies were excluded. The analysis focuses on three well differentiated
      areas: kidney transplant surgery, nephrectomies for malignant diseases, and
      nephrectomies for benign pathologies including a very specific subgroup that
      includes the infectious-inflammatory diseases. In parallel, we performed a
      bibliographic review in which more than 87,000 cases of open surgeries where
      referenced, adding the articles about laparoscopic nephrectomies published over
      the last decade. RESULTS: Global mortality of the series (the first 30
      postoperative days) was 0.8%, mostly cases of transplant nephrectomies (4), and
      one upper urinary tract transitional cell carcinoma. Significant morbidity
      appeared in 47 cases (8%), 15 of which (2.5%) required reoperation, being
      intensive bleeding with hypovolemia of variable severity the most frequent cause.
      The series includes non selected cases of a wide spectrum of pathologies. Any
      comparison with minimally invasive approaches should take into consideration,
      among other parameters, selection of the cases.

PMID- 16568696
TI  - [Adrenal myelolipoma. Case report and bibliographic review].
AB  - OBJECTIVES: We report one case of adrenal myelolipoma in a female patient
      presenting with right lumbar pain over six months. METHODS: Diagnostic work
      included ultrasound, intravenous urography (IVU) and CT scan. RESULTS: The
      patient underwent right adenomectomy with the working diagnosis of adrenal
      myelolipoma. We describe the pathology report. CONCLUSIONS: Myelolipoma may
      present hematopoietic, fat and bone components. It continues being an incidental
      finding. Ultrasound and CT scan are effective diagnostic tests. Asymptomatic
      small tumors, smaller than 4 cm, may be monitored with watchful waiting.
      Symptomatic tumors greater than 4 cm should be extirpated because of the risk of
      spontaneous rupture with retroperitoneal bleeding. Bilateral adrenalectomy for
      big tumors implies medical replacement with hydrocortisone.

PMID- 16568697
TI  - [Psoas muscle abscess: bibliographic review].
AB  - OBJECTIVES: To report the clinical characteristics, diagnosis and treatment of
      psoas abscess. METHODS/RESULTS: We report the case of a 77 year old female
      patient who was diagnosed of psoas abscess. Due to the unspecific symptoms, she
      was initially treated as a renal colic. Ultrasound was the test that oriented us
      to the diagnosis. Percutaneous drainage was effective, checking the resolution
      using CT Scan. CONCLUSIONS: Psoas abscess is an uncommon pathology the presenting
      features of which are usually unspecific. CT Scan is the astronomer diagnostic
      tests and percutaneous drainage has good results and is less aggressive
      therapeutic option for this disease.

PMID- 16568698
TI  - [Testicular microlithiasis].
AB  - OBJECTIVES: Testicular microlithiasis, characterized by the existence of
      microscopic calcifications within the seminiferous tubules, is rare, generally an
      incidental finding during a scrotal ultrasound. METHODS: We report the case of a
      45-year-old male without risk factors for the development of a germ cell
      testicular tumor with the diagnosis of bilateral testicular microlithiasis.
      RESULTS: The patient was followed yearly with testicular ultrasound, without
      evidence of germ cell tumor over a four-year follow-up period. CONCLUSIONS:
      Although the clinical significance of testicular microlithiasis is under debate
      due to the various controversies found in the literature about its association or
      not with testicular tumors, as well as the various protocols for initial
      management and adequate intervals for follow-up, it seems reasonable to perform
      an ultrasound yearly independently of the existence or not of associated risk
      factors.

PMID- 16568699
TI  - [Renal leiomyoma: case report].
AB  - OBJECTIVES: To report a new case of asymptomatic capsular leiomyoma. METHODS: 68
      year-old male asymptomatic patient who was diagnosed of solid mass after a
      radiological study (ultrasound and CT scan). RESULTS: The treatment of this
      neoplasia was radical nephrectomy, with an uneventful postoperative course and a
      pathology report of renal leiomyoma. CONCLUSIONS: Renal leiomyoma is a rare
      benign mesenchymal tumor that should be taken into consideration for the
      differential diagnosis of renal masses, because it would be an indication for
      nephron-sparing surgery; nevertheless, due to the difficulties to differentiate
      it from renal cell carcinoma it is not rare that the diagnosis is achieved after
      histological study of the nephrectomy specimen.

PMID- 16568700
TI  - [Concurrent tumors in a patient with giant hydronephrosis].
AB  - OBJECTIVES: Giant hydronephrosis, defined as the presence of a liquid volume over
      1000 ml within the urinary collector system, is a rare clinical entity, the
      diagnosis of which is an excellent exercise because it lacks of a defined
      clinical presentation. METHODS/RESULTS: We report the case of a 66-year-old male
      under study for a suspicious digestive tumor due to a long lasting clinical
      picture with severe cachexia, asthenia, anemia, constipation, and abdominal mass.
      Radiological tests showed a great right hydronephrosis secondary to a culculus in
      the ureteral-pelvic junction. Simple nephrectomy was performed, evacuating 7800
      ml of serous-hematic liquid from the pyelocalicial system. A histological
      diagnosis revealed the presence of multiple foci of transitional cell carcinoma
      and renal cell carcinoma associated. We review the diagnostic and therapeutic
      features in the literature. CONCLUSIONS: Giant hydronephrosis represents a
      diagnostic dilemma. It may present as an asymptomatic process, with clinical
      features of abdominal organs compression (bowel or urinary obstruction) or
      simulate abdominal tumors, massive ascites, or cystic retroperitoneal lesions.
      Simple nephrectomy is the treatment of choice in most cases, due to the advanced
      deterioration of the renal unit. Nevertheless, in some cases, in compromised
      patients, percutaneous drainage may be necessary as previous or definitive
      treatment to avoid changes in the hemodynamic balance secondary to the sudden
      abdominal decompression.

PMID- 16568701
TI  - [Metanephric stromal tumor: report of two cases and bibliographic review].
AB  - OBJECTIVE: Metanephric Stromal Tumors (MST) are pediatric renal neoplasms not
      very common in adults. This study revises its classification, incidence and
      evolution and also some specific characteristics of the cases diagnosed in
      adults. METHODS: We present two cases of MST diagnosed in adults of 72 and 77
      years old respectively. Abdominal pain due to a more than 4 Kg. mass was the
      initial presentation in both cases. The tumors were completely resected. Four and
      ten years after excision patients are alive without disease. RESULTS:
      Characteristic histologic features include a proliferation of fusocellular cells
      with alternating cellularity that imparts a nodular appearance and onion-skin
      cuffing around entrapped renal tubules or vascular structures. No mitoses or
      atypia was found but extensive necrosis and fibrosis were present. A majority of
      stromal cells were vimentine and CD-34 positive. Stains for CK and EMA
      highlighted entrapped native tubules. Both cases were previously classified as
      mesoblastic nephromas. According to the 2002 ONS classification of tumours of the
      urinary system, they have been revised and re-classified as MST CONCLUSION: MST
      are pediatric benign tumors exceptionally diagnosed in adults. Metanephric
      stromal tumors are divided into 3 categories based on the presence of epithelial
      cells, stroma and epithelial cells plus stromal. Complete excision is the
      treatment of choice and the prognosis is excellent.

PMID- 16568702
TI  - [Predominantly cystic renal metanephric adenoma. Case report].
AB  - OBJECTIVES: Metanephric adenoma is a relatively unfrequent asymptomatic
      embryogenic renal tumor which is generally diagnosed by an abdominal diagnostic
      tests indicated for other reasons. Differential diagnosis with benign and
      malignant tumors has to be performed. METHODS/RESULTS: We report one case of
      metanephric adenoma with intense necrotic-hemorrhagic and cystic changes with a
      size not previously referred in the literature. CONCLUSIONS: Cystic and
      hemorrhagic changes in benign renal tumors make differential diagnosis with
      malignant tumors mandatory Surgery is necessary in almost all cases and
      histologic study will give the diagnosis.

PMID- 16568703
TI  - [Massive hydronephrosis].

PMID- 16568704
TI  - Tuberous sclerosis complex. Forty-years of follow-up of a patient affected.
AB  - OBJECTIVES: To report the case of a patient diagnosed with tuberous sclerosis
      complex (TSC), describe its clinical features, diagnosis, and to attract
      attention on the fact that after 40 years of follow-up, the patient has presented
      practically all the manifestations described in the literature. METHODS: A 42
      year-old man diagnosed with.TSC presented the emergency department due to left
      lumbar pain and self-limited gross hematuria. On clinical examination patient was
      haemodynamically stable, but with decrease in haemoglobin (6.8 g/dL). Abdominal
      CT scan showed a 20 cm diameter heterogeneous mass in the left kidney suggesting
      hemorrhage of an angiomyolipoma. RESULTS: Left radical nephrectomy was performed
      and the pathological study of the surgical specimen confirmed the diagnosis of
      angiomyolipoma. Inmunohistochemical staining was positive with HMB-45.
      CONCLUSIONS: To recommend that patients with TSC be evaluated by a
      multidisciplinary group of clinicians, including urologists, neurologists and
      dermatologists. As patients with TSC survive into adulthood they will require
      more intervention by the urologist. CT scan is usually enough for the diagnosis
      of angiomyolipomas. Complete nephrectomy is appropriate when the whole kidney has
      been replaced by angiomyolipoma. The identification of molecular markers (HMB-45)
      facilitates histopathological diagnosis.

PMID- 16568705
TI  - [Transfer factor as specific immunomodulator in the treatment of moderate-severe
      atopic dermatitis].
AB  - BACKGROUND: Atopic dermatitis is a skin inflammatory disease which has been
      associated to high levels of IgE, eosinophiles and change of T lymphocytes. The
      transfer factor is an immunomodulator active substance and decreases the number
      of inflammatory cells and the severity of the symptoms of atopic dermatitis.
      OBJECTIVE: To determine the efficacy of the transfer factor as treatment of
      moderate and severe atopic dermatitis. MATERIAL AND METHODS: Articles related to
      treatment with transfer factor in the atopic dermatitis were looked up in Medline
      and EMBASE, and the ones referring to controlled studies in patients with
      moderate and severe atopic dermatitis in accord to SCORAD. RESULTS: We found
      seven articles with 121 patients and 88 controls demonstrating significant
      decrease in the symptoms of the SCORAD index, decreased IgE, and eosinophils in
      patients treated with transfer factor. CONCLUSIONS: The transfer factor is a
      choice treatment for moderate and severe atopic dermatitis.

PMID- 16568706
TI  - [Efficacy of mequitazine (Primalan) on the relief of symptoms of allergic
      rhinoconjunctivitis in children. Documented clinical experience].
AB  - OBJECTIVE: To assess the clinical efficacy of mequitazina in the relieve of
      symptoms of allergic rhinoconjunctivitis. PATIENTS AND METHODS: An open, non
      comparative, national multicenter study (performed by pediatricians, oto-rhino
      laryngologists and allergists of different states of Mexico), in order to
      describe the clinical experience related to treatmente efficacy with oral
      mequitazina in pediatric formulation about diminished characteristic symptoms of
      allergic rhinitis, assessed by the physician and patient. RESULTS: Physicians
      considered that efficacy was excellent in 42% of patients, very good in 38%, good
      in 16%, regular in 3% and bad in 0.2%. Patients assessed as: excellent in 47% of
      patients, very good in 35%, good in 15%, regular in 2% and bad in 1%. Only 5% of
      patients experienced adverse effects, which were transient and did not need
      treatment withdrawal. CONCLUSIONS: Mequitazina is an option to relieve symptoms
      of patients with allergic rhinoconjunctivitis.

PMID- 16568707
TI  - [Relation between IgE levels and infections in patients with allergic rhinitis
      and asthma].
AB  - BACKGROUND: High IgE levels are frequent in allergic patients. The relationship
      between allergy and infections is controversial. Some diseases with cellular
      immunodeficiencies as well as with infections have high IgE levels, such as:
      hyper-IgE, Netherton, Wiskott-Aldrich, DiGeorge syndromes, AIDS, etc. In a
      previous retrospective study we found a high percentage of concurrent infections
      (two or more simultaneous infections) in atopic patients with IgE levels above
      200 IU (OR 3.31; CI 95% 1.3 to 8.04; p < 0.01). The Th1/Th2 paradigm tries to
      explain the IgE elevation in atopy. A minor Th1 function would favor infectious
      processes by a reduction in TNF-alpha and IFNg. OBJECTIVE: To demonstrate if
      atopic patients with high IgE levels (> 200 IU) have more frequency of concurrent
      infections than patients with low levels. PATIENTS AND METHODS: In a cross
      sectional study we included patients with atopic rhinitis, asthma or both, in
      order to find upper and lower respiratory tract infections. RESULTS: We studied
      143 patients (IgE mean, 389.07; SD 606.21). IgE levels were higher in children
      (521.25 UI) than in adults (204.03 UI) (p < 0.05). 73.44% of the patients had
      sinusitis; 5.59% pharyngotonsillitis; 17.93% otitis, and 7.74% laryngitis,
      without IgE mean differences. 42.84% had concurrent infections (IgE 296.16 IU) vs
      57.15% without this processes (460.4 IU) (p = 0.11). When IgE levels were
      classified in high and low levels, with 200 IU as end point, we did not find
      differences in the number of infectious diseases. CONCLUSIONS: In this study high
      IgE levels did not have correlation with the higher frequency of concurrent
      infections.

PMID- 16568708
TI  - [Safety and efficacy of specific sublingual immunotherapy in patients with asthma
      and allergy to Dermatophagoides pteronyssinus].
AB  - BACKGROUND: First reports on sublingual immunotherapy were published in 1980.
      OBJECTIVE: To compare safety and effectiveness of sublingual immunotherapy, as
      compared with placebo, in asthmatic patients. MATERIALS: In a blinded randomized
      controlled trial asthmatic patients with positive skin prick tests to
      Dermatophagoides pteronyssinus, and with serum IgE at least 200 UI were included.
      According to GINA, asthma severity was mild persistent and moderate. All patients
      improved their baseline FEV1 at least by 14% after inhaled albuterol. Spirometry
      was performed again after three and six months after initiating treatment.
      Patients were randomized to receive for six months either sublingual
      immunotherapy with Der p 1 standardized allergens (IPI-ASAC, Mexico) at a total
      dose of 10,469 UBE or identically looking and tasting placebo. Both groups
      received conventional pharmacological therapy. RESULTS: Sixty four patients enter
      the study; four were excluded because of systemic oral steroid therapy. Sixty
      patients underwent randomization. Both groups (30 patients in each one) were
      similar in their baseline characteristics. After six months, patients that
      received sublingual immunotherapy had less exacerbations than those in the
      control group (61 vs 123, T 2.61, p<0.001, IC 1.8-7.2), better FEV1 as compared
      with baseline values (25% vs 9%, Z=0.66, p=0.03), and less need of albuterol (50%
      of initial dose, vs 21% (Z=1.4, p=0.03, IC 1.39-1.49). CONCLUSION: Sublingual
      immunotherapy improves patient symptoms and pulmonary functional tests, makes
      exacerbations less frequent, and reduces albuterol needs. It may improve asthma
      related quality of life.

PMID- 16568710
TI  - [Occupational asthma and reactive airway dysfunction syndrome].
AB  - Occupational asthma could be defined as a reversible lung disorder characterized
      by attacks of breathing difficulty, wheezing, and cough, which are caused by
      various agents found in the workplace. Incidence varies from 2 to 15% in adult
      work population; actually there is no data for the child population. Allergic
      occupational asthma is due to allergic sensitization to a specific substance or
      material present at the workplace; non-allergic occupational asthma occurs
      because of the high exposure to an irritant also at the workplace. Over the past
      few years, more people have been diagnosed as having asthma because of some
      workplace exposure. The identification of occupational asthma in workers is
      important because early detection may lead to the control of the worker's
      symptoms and control of the chemicals in the workplace. In Latin America there is
      no data about occupational asthma, maybe for the scarce information about it or
      for its difficult diagnosis.

PMID- 16568709
TI  - [Prevalence of positive skin tests to indoor allergens in preschooler children
      with respiratory allergy in Merida, Yucatan, Mexico].
AB  - BACKGROUND: Infantile asthma and rhinitis are commonly thought to be caused by
      indoor allergens but preschooler children are not commonly skin tested.
      OBJECTIVE: To know the frequency of skin test reactivity to indoor allergens in
      allergic preschooler children. MATERIAL AND METHODS: We evaluated 176 children
      (103 females/73 males) between 2 and 5 years old with respiratory allergy. All of
      the children tested had at least one positive skin test (house dust mite,
      cockroach, dog, feathers, and cat). RESULTS: Seventy seven children had allergic
      rhinitis (44%), 68 had asthma and rhinitis (39%), and 31 had only asthma (18%).
      One hundred thirty two (75%) of the children were skin test positive to house
      dust mite, 91 (52%) to cockroach, 31 (18%) to dog, 25 (14%) to feathers, and 24
      (14%) to cat. Furthermore, the frequency of sensitization to house dust mite has
      an increase associated with the age of the patients with a significant difference
      at 5 years old (odds ratio=11.63, I.C. 95%=3.83-37.10; p <0.001). CONCLUSIONS:
      The most frequent indoor allergen was house dust mite, with a trend directly
      proportional to age of the patients.

PMID- 16568711
TI  - [Reactive airway dysfunction syndrome. Clinical case].
AB  - The reactive airway dysfunction syndrome (RADS) is a type of occupational asthma
      without any period of latency and induced by irritants of low molecular weight.
      It is a clinical illness diagnosed with scarce information of prevalence in our
      medical service, that is why it receives a deficient treatment with more
      morbidity. A clinical case of a 60 year old patient is reported with a sudden,
      intense and long exposure to clorhidric acid and the consequent development of
      RADS. We performed a complete study of her signs and symptoms as well as some
      diagnostic tests, such as respiratory function tests and a positive test to the
      clorhidric acid. Once the diagnosis was confirmed, the patient was treated with
      high doses of corticosteroids and bronchodilators of long action for a period of
      three months. She had complete remission of symptoms, with normal respiratory
      tests and return to her every day work activities. It is important to consider
      that this illness in patients with respiratory symptoms and exposed to irritants
      should receive an appropriate treatment, which makes a better prognosis of it.

PMID- 16568712
TI  - Thioviridamide, a novel apoptosis inducer in transformed cells from Streptomyces
      olivoviridis.
AB  - In the course of screening for antitumor antibiotics using 3Y1 rat fibroblasts
      transformed with adenovirus oncogenes, a new active substance designated
      thioviridamide was isolated from the culture broth of an actinomycete. The
      producing organism was identified as Streptomyces olivoviridis on the basis of
      its culture characteristics and physiological properties. Thioviridamide showed
      cytotoxicity selectively against Ad12-3Y1 cells (IC50 = 3.9 ng/ml) and E1A-3Y1
      cells (IC50 = 32 ng/ml), both of which contain the adenovirus E1A oncogene.
      Significant numbers of Ad12-3Y1 cells treated with thioviridamide contained
      condensed chromatin and fragmented nuclei, indicating that thioviridamide induced
      apoptosis.

PMID- 16568713
TI  - Structure of thioviridamide, a novel apoptosis inducer from Streptomyces
      olivoviridis.
AB  - A novel apoptosis inducer, thioviridamide, was isolated from an actinomycete
      identified as Streptomyces olivoviridis. The molecular formula of thioviridamide
      was determined to be C56H93N14O10S7+ from high-resolution FAB-MS. The structure
      of thioviridamide was analyzed by NMR spectral analysis including a variety of
      two-dimensional techniques. COSY and HMBC experiments revealed the presence of a
      2-hydroxy-2-methyl-4-oxopentanoyl group and eleven amino acid residues including
      two novel amino acids, beta-hydroxy-N1,N3-dimethylhistidinium and S-(2
      aminovinyl)cysteine. 1H-13C long-range correlations observed in the HMBC, CT-HMBC
      and HMBC-HOHAHA spectra connected the partial structures with seven amide
      linkages and five thioamide linkages to establish the planar structure of
      thioviridamide as a unique cyclic peptide.

PMID- 16568714
TI  - A new teleocidin analog from Streptomyces sp. MM216-87F4 induces substance P
      release from rat dorsal root ganglion neurons.
AB  - A new teleocidin analog was isolated from the fermentation medium of Streptomyces
      sp. MM216-87F4 and its structure was elucidated as 14-O-(N-acetylglucosaminyl)
      teleocidin A (GlcNAc-TA). GlcNAc-TA induces the translocation of protein kinases
      Calpha and theta fused with enhanced green fluorescent protein (PKCalpha-EGFP and
      PKCtheta-EGFP) to the plasma membrane in stable transfectants, and reduces
      intracellular calcium mobilization induced by agonists of G-protein coupled
      receptors in various cell lines without causing irritation of the mouse ear.
      Further, GlcNAc-TA sensitizes the release of excitatory neuropeptides substance P
      induced by capsaicin from primary-cultured dorsal root ganglion (DRG) neurons of
      the rat and GlcNAc-TA alone also triggers substance P release in a dose-dependent
      manner. This study provides the first observation that a teleocidin analog
      without a free hydroxyl group at C-14 acts as a PKC activator and directly
      induces the release of excitatory neuropeptide.

PMID- 16568715
TI  - DNA sequencing and transcriptional analysis of the kasugamycin biosynthetic gene
      cluster from Streptomyces kasugaensis M338-M1.
AB  - Streptomyces kasugaensis M338-M1 produces the aminoglycoside antibiotic
      kasugamycin (KSM). We previously cloned, sequenced and characterized the KSM
      acetyltransferase, transporter, and some of the biosynthetic genes from this
      strain. To identify other potential genes in a chromosome walk experiment, a 6.8
      kb EcoRI-PstI region immediately downstream from the KSM transporter genes was
      sequenced. Five open reading frames (designated as kasN, kasO, kasP, kasQ, kasR)
      and the 5' region of kasA were found in this region. The genes are apparently co
      transcribed as bicistrons, all of which are co-directional except for the kasPQ
      transcript. Homology analysis of the deduced products of kasN, kasP, kasQ and
      kasR revealed similarities with known enzymes: KasN, D-amino acid oxidase from
      Pseudomonas aeruginosa (35% identity); KasP, F420-dependent H4MPT reductase from
      Streptomyces lavendulae (33% identity); KasQ, UDP-N-acetylglucosamine 2-epimerase
      from Streptomyces verticillus (45% identity); and KasR, NDP-hexose 3,4
      dehydratase from Streptomyces cyanogenus (38% identity); respectively. A gel
      retardation assay showed that KasT, a putative pathway-specific regulator for
      this gene cluster, bound to the upstream region of kasN and to the intergenic
      region of kasQ-kasR, suggesting that the expression of these operons is under the
      control of the regulator protein.

PMID- 16568716
TI  - SPF-32629 A and B, novel human chymase inhibitors produced by Penicillium sp.
AB  - Two new human chymase inhibitors, SPF-32629A and B, were isolated from the
      cultured broth of Penicillium sp. SPF-32629. These structures were determined by
      spectroscopic methods and identified as new pyridone compounds. SPF-32629B was
      the carboxylated derivative of SPF-32629A. SPF-32629A and B specifically
      inhibited human chymase among four serine proteases tested with the IC50 of 0.25
      and 0.42 microg/ml, respectively.

PMID- 16568718
TI  - The complete biosynthetic gene cluster of the 28-membered polyketide
      macrolactones, halstoctacosanolides, from Streptomyces halstedii HC34.
AB  - Halstoctacoanolides A and B are 28-membered polyketide macrolactones and were
      isolated from Streptomyces halstedii HC34. The biosynthetic gene cluster (hls
      cluster) of halstoctacosanolides was completely identified from the genome
      library of Streptomyces halstedii HC34. DNA sequence analysis of ca. 100 kb
      region revealed that there were seven type I polyketide synthases (PKSs) and two
      cytochrome P450 monooxygenases in this cluster. Involvement of the gene cluster
      in the halstoctacosanolide biosynthesis was demonstrated by the gene disruption
      of P450 monooxygenase genes. The mutants produced a new deoxygenated
      halstoctacosanolide derivative, halstoctacosanolide C, which confirmed that the
      hls gene cluster was essential for the biosynthesis of halstoctacosanolides.

PMID- 16568717
TI  - Inhibition of lipopolysaccharide activity by a bacterial cyclic lipopeptide
      surfactin.
AB  - Compounds that inactivate lipopolysaccharide (LPS) activity have the potential of
      being new anti-inflammatory agents. Therefore, we searched among microbial
      secondary metabolites for compounds that inhibited LPS-stimulated adhesion
      between human umbilical vein endothelial cells (HUVEC) and HL-60 cells. By this
      screening, we found a cyclic lipopeptide surfactin from the culture broth of
      Bacillus sp. BML752-121F2 to be inhibitory. The addition of the surfactin prior
      to the LPS stimulation decreased HL-60 cell-HUVEC adhesion without showing any
      cytotoxicity. We confirmed that surfactin inhibited LPS-induced expression of
      ICAM-1 and VCAM-1 in HUVEC. It also inhibited the cellular adhesion induced by
      lipid A, the active component of LPS; but it did not inhibit TNF-alpha or IL-1
      beta-induced cell adhesion. Then, surfactin was shown to suppress the interaction
      of lipid A with LPS-binding protein (LBP) that mediates the transport of LPS to
      its receptors. Finally, surface plasmon resonance (SPR) analysis revealed the
      surfactin to interact reversibly with lipid A. Thus, this Bacillus surfactin was
      shown to be an inhibitor of LPS-induced signal transduction, directly interacting
      with LPS.

PMID- 16568719
TI  - The dasyscyphins A-C and niveulone, new biologically active compounds from the
      ascomycete Dasyscyphus niveus.
AB  - In the course of a screening for cytotoxic compounds from fungi four new
      terpenoid metabolites, named dasyscyphins A, B, C, and niveulone were isolated
      from fermentations of Dasyscyphus niveus strain A0101. While dasyscyphin A (1)
      exhibited no significant biological activities in our test systems dasyscyphin B
      (2) and dasyscyphin C (3) showed cytotoxic activities against human (HepG2, Hela
      S3, U937, Colo-320, Jurkat) cell lines with IC50-values of 0.5-3 microg/ml while
      the activity of niveulone (4) was less pronounced. Only modest or weak antibiotic
      properties were observed for (2) and (3).

PMID- 16568720
TI  - Niveulone, a heterocyclic spiro terpenoid from the ascomycete Dasyscyphus niveus.
AB  - The new heterocyclic spiro terpenoid niveulone (1) was isolated from the cultural
      fluid of the ascomycete Dasyscyphus niveus, and its chemical structure and
      relative configuration were determined by spectroscopic techniques.

PMID- 16568721
TI  - Aberrant p53 expression and the development of gallbladder carcinoma and adenoma.
AB  - Gallbladder carcinoma (GBC) is a highly lethal but relatively rare neoplasm of
      the digestive tract. The progression from gallbladder adenoma to carcinoma
      remains unclear. The p53 gene is the most frequently mutated tumor suppressor in
      human cancers. In this study, we analyzed the expression patterns of the p53
      protein in 22 cases of GBC, 17 cases of precursor lesions (16 gallbladder
      adenomas and 1 cystadenoma), and 15 cases of normal epithelia using
      immunohistochemical analysis. The results were correlated with clinicopathologic
      characteristics. We found that p53 expression was significantly increased in
      59.1% (13/22) of GBC cases and in 17.6% (3/17) of gallbladder adenoma cases (p =
      0.009). There was no p53 expression in the 15 cases of normal epithelia, and a
      significant difference was shown between normal epithelium and GBC cases (p <
      0.001). In addition, the expression pattern of p53 protein did not show any
      significant correlation with the histologic type and the differentiation grade of
      GBC. In conclusion, we suggest that the aberrant p53 expression may play a role
      in the occurrence of GBC.

PMID- 16568722
TI  - Effects of antiglaucoma drugs on calcium mobility in cultured corneal endothelial
      cells.
AB  - The aim of this study was to estimate the effects of various antiglaucoma drugs
      including betaxolol, timolol, levobunolol, brimonidine, carteolol, dipivefrin,
      dorzolamide, brinzolamide, latanoprost, unoprostone, and pilocarpine on
      intracellular free Ca2+ ([Ca2+]i) mobility in cultured bovine corneal endothelial
      cells. Various antiglaucoma drugs were diluted from original concentrations to 1/
      100, 1/ 1,000, and 1/ 10,000. The [Ca2+] mobility was studied by
      spectrofluorophotometry after loading with the ester of fura-2 (fura-2/AM). It
      was found that timolol (58 microM and 5.8 microM), levobunolol (171 microM, 17.1
      microM, and 1.71 microM), betaxolol (162 microM, 16.2 microM, and 1.62 microM),
      carteolol (680 microM and 68 microM), dipivefrin (28 microM and 2.8 microM),
      dorzolamide (616 microM and 61.6 microM), brinzolamide (260 microM), latanoprost
      (1.1 microM), unoprostone (28.2 microM, 2.82 microM, and 0.282 microM), and
      pilocarpine (408 micro and 40.8 microM) induced a significant increase in
      [Ca2+]i. Nevertheless, only brimonidine (68 microM and 6.8 microM) decreased
      [Ca2+]i concentration significantly. Benzalkonium chloride preservative did not
      affect [Ca2+]i after addition of 0.001, 0.0001 and 0.00001 mg/mL to cells. These
      results indicate that all antiglaucoma drugs may affect the physiologic function
      of corneal endothelial cells through change of [Ca2+]i mobility.

PMID- 16568723
TI  - Doxepin has a potent and long-acting spinal anesthetic effect in rats.
AB  - Doxepin, a tricyclic antidepressant, was recently found to be effective in the
      treatment of various acute and chronic painful conditions. However, the mechanism
      of its actions was not clear, especially when involving the spine. The aim of our
      study was to evaluate the spinal anesthetic effect of doxepin. Two commonly used
      traditional local anesthetics, bupivacaine and lidocaine, were used as controls.
      The potencies and durations of the drugs' action were evaluated in male Sprague
      Dawley rats. We found that intrathecally administered doxepin, like bupivacaine
      and lidocaine, produced dose-related spinal anesthetic effects on motor activity,
      proprioception, and nociception. Among the three drugs, doxepin produced spinal
      anesthetic effects in rats more potent than that of lidocaine (p < 0.001, in each
      comparison) and longer than that of bupivacaine and lidocaine (p < 0.001, in each
      comparison). The spinal activity of doxepin may provide some explanation of its
      clinical effect in pain management.

PMID- 16568724
TI  - Wisconsin Card Sorting Test performance after putaminal hemorrhagic stroke.
AB  - The purpose of this study was to compare the performance differences in the
      Wisconsin Card Sorting Test (WCST) between 55 patients with putaminal hemorrhage
      (PH) 3 months after stroke and 69 age-matched normal controls. Impairment on WCST
      was defined as performance greater than 1.64 standard deviation below the control
      mean. A multivariate analysis of covariance (MANCOVA) controlling for education
      yielded a significant main effect for group but not for education and interaction
      of group x education. Univariate analyses revealed significant between-group
      differences in five WCST measures, including perseverative errors (PE),
      perseverative responses (PR), conceptual-level responses (CLR), number of
      categories completed (NCC), and trials to complete the first category (TCC). For
      patients with PH, z-scores for two WCST indices were within the impaired range:
      TCC and PR. A high percentage of patients (40-47%) scored in the designated
      impaired range on NCC, PR, PE, and TCC. The WCST variables discriminated patients
      from controls with an overall accurate classification rate of 91.9%. Of these,
      the variables that contributed most to the differentiation between patients and
      normal controls were PE, CLR, and total number correct (TNC) (a standardized
      canonical discriminant function coefficient > 0.40). Finally, no significant
      hemispheric laterality effects emerged on any of the WCST variables. The results
      of this study provide further evidence of impaired mental set shifting in stroke
      patients with PH. The implications for rehabilitation professionals are
      discussed, and recommendations for further research are made.

PMID- 16568725
TI  - Paraneoplastic hypercalcemia with metastatic calcification--clinicopathologic
      studies.
AB  - Hypercalcemia is a common paraneoplastic syndrome that may result in metastatic
      calcification. We report here on four autopsy cases with paraneoplastic
      hypercalcemia with metastatic calcification, to evaluate the clinicopathologic
      manifestations. All were males, aged 37-63 years old. Primary tumors included one
      transitional cell carcinoma of the urinary bladder, one multiple myeloma, and two
      squamous cell carcinomas of the esophagus. Calcium concentrations ranged from 3.3
      to 5.9 mmol/L. Chronic hypercalcemia resulted in metastatic calcification. The
      kidney and stomach were the most vulnerable organs. Only case 1 presented with an
      increase in plasma calcium above 5 mmol/L (about twice the normal value); the
      metastatic calcification involved the capillary walls of his lungs, and he died
      of fulminant pulmonary edema. Our conclusion is that judicious treatment for
      paraneoplastic hypercalcemia is important with respect to the occurrence of
      pulmonary edema associated with metastatic calcification.

PMID- 16568726
TI  - Spontaneous pneumothorax as a complication of septic pulmonary embolism in an
      intravenous drug user: a case report.
AB  - Infective endocarditis has been the major cause of morbidity and mortality among
      intravenous drug users (IDUs) with infections, mostly involving the tricuspid
      valve and presenting multiple septic pulmonary embolisms. Numerous pulmonary
      complications of septic pulmonary embolism have been described, but only a few
      have reported spontaneous pneumothorax. Our patient, a 23-year-old heroin addict,
      was hospitalized for tricuspid endocarditis and septic pulmonary embolism. Acute
      onset of respiratory distress occurred on his seventh hospital day and rapidly
      resulted in hypoxemia. Immediate bedside chest radiograph demonstrated left
      pneumothorax. It was thought to be a spontaneous pneumothorax, because he had not
      undergone any invasive procedure before the occurrence of pneumothorax. His
      clinical condition improved after the insertion of an intercostal chest tube. He
      later underwent surgery to replace the tricuspid valve as a result of the large
      size of the vegetation and poor control of infection. He ultimately survived.
      Pneumothorax is a possible lethal complication of septic pulmonary embolism in
      IDUs with right-sided endocarditis and should be considered in such patients when
      respiratory distress occurs acutely during their hospitalization.

PMID- 16568727
TI  - Acute respiratory distress syndrome associated with rabies: a case report.
AB  - Acute respiratory distress syndrome (ARDS) is the first potentially lethal
      complication in rabies virus infection, although its occurrence is rare. We
      report on a fatal case of rabies virus infection in a 45-year-old woman from Hu
      Nan Province, China. The neurologic signs of limb numbness and water phobia
      occurred from 61 days after the dog bite; the clinical course was progressive,
      with the most severe clinical manifestations being fever, encephalitis, and ARDS.
      The woman expired 12 days after admission to the hospital. An autopsy proved
      rabies encephalitis, mainly involving the medulla oblongata, the thalamus, part
      of the pons, the cerebellum, and the hippocampus. The lung pathologic examination
      revealed the organizing phase of ARDS with diffuse alveolar damage, hyaline
      membrane formation, type II alveolar cell hyperplasia accompanied by
      proliferation of fibroblasts and infiltration of mononuclear cells into the
      interstitial space. Immunohistochemistry stain and reverse transcription
      polymerase chain reaction for rabies virus failed to demonstrate the organism in
      the lung tissue. Strong expression of inducible nitric oxide synthase (iNOS) was
      detected in the alveolar macrophages. An immunologic mechanism with iNOS
      expression in the absence of direct invasion of the organism may participate in
      the pathogenesis of ARDS associated with rabies.

PMID- 16568728
TI  - Colon perforation: a rare complication during percutaneous nephrolithotomy.
AB  - Only a few cases of colon perforation during percutaneous nephrolithotomy (PCNL)
      have been reported. We present here a case of colon perforation during PCNL that
      was managed conservatively by stenting the urinary tract, using the percutaneous
      catheter as the colostomy tube, and giving broad-spectrum antibiotics. This
      report also reviews the anatomic and technical access to the kidney and reminds
      the urologist about this rare but serious complication of PCNL.

PMID- 16568729
TI  - [Writing is a duty...].

PMID- 16568730
TI  - [Controversy about the Association of Nurses. Interview with Stephane Lambert
      about gathering information by Yasmie Ouharzoune].

PMID- 16568732
TI  - [Everyday life in psychiatry].

PMID- 16568731
TI  - [Putting in place the specialized mobile personnel in psychiatry].

PMID- 16568734
TI  - [Everyday life does not exist, it is being construed...].

PMID- 16568733
TI  - [The shared everyday life, the area of care that cannot be made trivial].

PMID- 16568735
TI  - [Certain activities, when doing nothing can make a difference].

PMID- 16568736
TI  - [The history of flesh, the history of skin].

PMID- 16568737
TI  - [Care without a recipe].

PMID- 16568738
TI  - [Following protocols: a road toward professionalism?].

PMID- 16568739
TI  - [Estimating the risk of flu epidemics in psychiatry].

PMID- 16568740
TI  - Texas act treads on environmental scientists.

PMID- 16568741
TI  - Fraud in science.

PMID- 16568742
TI  - Leftovers may explain perfluorinated compound puzzle.

PMID- 16568743
TI  - The cloudy side of sunscreens.

PMID- 16568744
TI  - Another danger for developing frogs.

PMID- 16568745
TI  - The next generation of nuclear power?

PMID- 16568746
TI  - Control of mercury emissions from coal-fired electric utility boilers.

PMID- 16568747
TI  - Integrated assessment of the spatial variability of ozone impacts from emissions
      of nitrogen oxides.
AB  - This paper examines the ozone (O3) damages caused by nitrogen oxides (NO(x))
      emissions in different locations around the Atlanta metropolitan area during a
      summer month. We calculate O3 impacts using a new integrated assessment model
      that links pollution emissions to their chemical transformation, transport,
      population exposures, and effects on human health. We find that increased NO(x)
      emissions in rural areas around Atlanta increase human exposure to ambient O3
      twice as much as suburban emissions. However, increased NO(x) emissions in
      central city Atlanta actually reduce O3 exposures. For downtown emissions, the
      reduction in human exposures to O3 from titration by NO in the central city
      outweighs the effects from increased downwind O3. The results indicate that the
      marginal damage from NO(x) emissions varies greatly across a metropolitan area.
      The results raise concerns if cap and trade regulations cause emissions to
      migrate toward higher marginal damage locations.

PMID- 16568748
TI  - Environmental risks of nanotechnology: National Nanotechnology Initiative
      funding, 2000-2004.
AB  - By considering risk in the early stages of a technology, costs of identifying
      important health and environmental impacts after a technology has widely diffused
      can be avoided. Nanotechnology, involving materials and objects less than 100 nm
      in size, is an important case in point. In this paper we analyze the research
      priorities discussed by various interest groups concerned with the environmental
      risks of nanotechnology, evaluate the distribution of federal environmental
      nanotechnology R&D funding, and discuss research in this field. Overall federal
      environmental R&D funding to date is limited and focuses more on the positive
      environmental applications of nanotechnology than on basic knowledge/research,
      tools for nanoenvironmental research, or the potential risks of nanotechnology.
      The situation began to change in 2004 when a significant increase occurred in
      federal R&D funding for the environmental implications of engineered
      nanomaterials. Though literature exits on the exposure, transport, and toxicity
      of incidental nanoparticles, little work has been published on the environmental
      risks of engineered nanoparticles.

PMID- 16568749
TI  - Mass loading and fate of perfluoroalkyl surfactants in wastewater treatment
      plants.
AB  - Wastewater treatment plants have recently been identified as a significant
      pathway for the introduction of perfluoroalkyl surfactants (PASs) to natural
      waters. In this study, we measured concentrations and fate of several PASs in six
      wastewater treatment plants (WWTPs) in New York State. We also monitored and
      measured matrix effects (ionization suppression and enhancement) by postcolumn
      infusion and standard additions. Concentrations of perfluorooctanoate (PFOA) in
      effluents of the six WWTPs ranged from 58 to 1050 ng/L. Perfluorooctanesulfonate
      (PFOS) was also ubiquitous in effluents of these WWTPs, albeit at much lower
      concentrations (3-68 ng/L). Two of these WWTPs employed identical treatment
      processes, with similar hydraulic retentions, but differed only in that Plant B
      treated domestic and commercial waste, whereas Plant A had an additional
      industrial influence. We found that this industrial influence resulted in
      significantly greater mass flows of all of the PASs analyzed. Primary treatment
      was found to have no effect on the mass flows of PASs. Secondary treatment by
      activated sludge in Plant A significantly increased (p < 0.05) the mass flows of
      PFOS, PFOA, perfluorononanoate (PFNA), perfluorodecanoate (PFDA), and
      perfluoroundecanoate (PFUnDA). However, in Plant B, only the mass flow of PFOA
      was significantly increased. The observed increase in mass flow of several PASs
      may have resulted from biodegradation of precursor compounds such as
      fluorotelomer alcohols, which is supported by significant correlations in the
      mass flow of PFOA/PFNA and PFDA/PFUnDA. Furthermore, the masses of PFDA and
      PFUnDA were significantly correlated only after the secondary treatment. In Plant
      A, concentrations of odd-number PFCAs were greater than those of even-number
      PFCAs, and concentration decreased with increasing chain length (from C8 to C12).
      A different pattern was observed in sludge samples, in which the dominance of
      PFOA decreased, and PFDA and PFUnDA increased, suggesting preferential
      partitioning of longer-chain PFCAs to sludge.

PMID- 16568750
TI  - Identification of Ah receptor agonists in sediment of Meiliang Bay, Taihu Lake,
      China.
AB  - Deterioration of ecosystem and water quality in Taihu Lake, the third largest
      freshwater lake in China, is of great concern in China. However, most evaluations
      on water and sediment were carried out by chemical analysis, which could hardly
      gain information on the risk stressors affecting the system. Sediment samples
      from Meiliang Bay, Taihu Lake were assayed for AhR-mediated EROD induction using
      a rat hepatoma cell line (H4IIE). The known AhR agonists including PCDD/Fs, PCBs,
      and PAHs were analyzed by instruments. The cause-effect relationship between the
      observed EROD activity and chemical concentrations of AhR agonists and their dose
      effect relationship were examined. Our results showed that sediment extracts
      could induce significant AhR effects, and the chemical-derived TCDD equivalents
      (TEQ(cal)) were significantly correlated to bioassay-derived TCDD equivalents
      (TEQ(bio)) (R = 0.85, p < 0.01). Among different contributors, PAHs could account
      for 70-93% and PCDD/Fs could contribute less than 30% of TEQ(cal). PCBs exhibited
      almost no contribution. Therefore, integration of EROD bioassay and chemical
      analysis provided an effective way for identifying the potential risk stressors.
      Underthis circumstance, a quantitative dose--effect relationship between TEQ(PAH)
      and EROD activity could be established, suggesting that the observed AhR effect
      was mostly derived from PAHs. The implication is that the EROD assay and the
      identified risk stressors (PAHs) may be used in lieu of detailed environmental
      analysis to follow the progression of a remediation strategy.

PMID- 16568751
TI  - Physical-chemical and maternal determinants of the accumulation of organochlorine
      compounds in four-year-old children.
AB  - A cohort study representing a general population (Minorca Island, birth year 1997
      1998) showed that in utero transfer of organochlorine compounds (OCs) in children
      was strongly correlated with the age of the mother and, in the case of
      hexachlorobenzene (HCB), 4,4'-DDE, and 4,4'-DDT, with the maternal body mass
      index. Some of these correlations remained significant for the serum
      concentrations collected in these children at four years. No significant
      correlations with length of gestation were observed. Breastfeeding and age of
      lactation were strong determinants of most OC concentrations at four years of
      age. At this age, the body burden of these compounds was higher than at birth
      irrespective of maternal or formula feeding, but they accumulated at higher
      extent in the former case involving concentration increments in blood that
      surpassed the growth dilution effects, with the only exceptions being
      pentachlorobenzene (PeCB), HCB, and 4,4'-DDT. 4,4'-DDE exhibited the highest
      increase in association with breastfeeding, pointing to a specific accumulation
      pathway via this mode. Compounds with low K(ow) values such as beta
      hexachlorocyclohexane showed significant accumulation in four-year-old children
      but with small differences between the groups that had been raised on either
      breast milk or formula. Compounds having low K(oa) values such as HCB showed
      decreases in concentration and small body burden variation between birth and four
      years of age, which points to their preferential elimination in these initial
      periods of infant growth.

PMID- 16568752
TI  - Occurrence of UV filters 4-methylbenzylidene camphor and octocrylene in fish from
      various Swiss rivers with inputs from wastewater treatment plants.
AB  - UV filters are widely used compounds in many personal care products and
      cosmetics, such as sunscreens. After use, UV filters are washed off from skin and
      clothes and enter the aquatic environment. Recent studies indicate that some
      lipophilic UV filters do accumulate in biota and act as endocrine disruptors. In
      this study, concentrations of 4-MBC (4-methylbenzylidene camphor) and OC
      (octocrylene), two widely used UV filters, were determined in the muscle tissue
      of fish (brown trout, Salmo trutta fario) from seven small Swiss rivers, all
      receiving inputs from wastewater treatment plants (WWTPs). Lipid-weight based
      concentrations of up to 1800 (4-MBC) and 2400 ng g(-1) (OC) were found. These
      levels were distinctly higher than those previously observed in white fish
      (Coregonus sp.) and roach (Rutilus rutilus) from Swiss lakes with inputs from
      WWTPs. This suggests a higher availability of these contaminants for fish in
      rivers than in lakes and identifies WWTPs as a major source for UV filters in the
      aquatic environment. As compared to lake fish, individual fish from a river
      showed much greater variation in 4-MBC and OC concentrations, likely as a result
      of a wider range of exposure in rivers than in lakes. 4-MBC concentrations
      correlated reasonably well with concentrations of methyl triclosan, a chemical
      marker for lipophilic WWTP-derived contaminants. The ratio P/Q of population (P)
      in a watershed to water throughflow (Q) is considered to be a measure of the
      domestic burden from WWTPs. A correlation of methyl triclosan with P/Q was
      previously observed with lake fish. However, such a correlation could not be
      confirmed with river fish. The higher average concentrations of OC as compared to
      4-MBC in river fish, and the fact that OC was mostly absent in lake fish,
      suggests differences in bioaccumulation and availability of these two UV filters.

PMID- 16568753
TI  - Demographic and lifestyle factors associated with dioxin-like activity (CALUX
      TEQ) in human breast milk in Hong Kong.
AB  - Maternal exposure to dioxins and related compounds before conception may affect
      the health of the fetus. To identify factors affecting dioxin body load in Hong
      Kong, in 2002, total dioxin-like activity was estimated in 250 individual milk
      samples at 2-6 weeks postpartum, from a representative group of primiparous
      mothers, aged 18-42 years (mean 29 +/- 5 years), by a chemically activated
      luciferase expression (CALUX) bioassay. Associations between the CALUX-TEQ and 20
      socio-demographic and dietary variables were examined separately in mothers
      younger than 30 years (n = 114) and 30 years or older (n = 119), by multiple
      linear regression analysis. CALUX-TEQ (mean 14.5 +/- 5.8 pg/g fat) significantly
      increased by 0.4-0.5 pg/g fat for every year of the mother's age. Mothers born in
      Guangdong province of China had a significantly higher CALUX-TEQ. Higher seafood
      consumption (older mothers; p = 0.07) and having a female baby (younger mothers;
      p = 0.002) were associated with a higher maternal CALUX-TEQ level. Age was the
      strongest factor affecting human dioxin levels in Hong Kong. Birthplace and
      residence are important indicators of variations in exposure to environmental
      pollution in the Asia Pacific region. Temporal trends in body loads of dioxins
      remain to be established and continuous monitoring of dioxins in humans and foods
      is necessary as a precautionary approach to guide environmental control measures
      and prevent exposure to infants.

PMID- 16568754
TI  - Mercury bioaccumulation in forage fish communities invaded by rainbow smelt
      (Osmerus mordax).
AB  - We compared total mercury concentrations ([Hg]) among 6 forage fish species in 25
      central Canadian lakes and related [Hg] to adjusted-delta15N (an index of trophic
      position), delta13C, growth rate, and a suite of environmental variables. Growth
      rates were also compared among species and related to environmental variables. We
      found that rainbow smelt (Osmerus mordax), a recent invader in many of these
      lakes, had intermediate [Hg] and growth rates relative to other species. Forage
      fish growth rates differed significantly among species and were related to
      latitude (inverse relationship) and lake conductivity (positive relationship).
      Mercury concentrations also differed significantly among species and the
      strongest predictors were growth rate and lake conductivity; [Hg] was
      significantly and negatively related to both. Adjusted-delta15N explained very
      little variation in [Hg] and was significant only when the analysis was
      restricted to biotic variables. These results indicate that biomagnification may
      not be observed at fine scales of trophic differentiation and that rainbow smelt
      are unlikely to cause post-invasion [Hg] increases in most predatory fish
      species.

PMID- 16568755
TI  - Significant residual fluorinated alcohols present in various fluorinated
      materials.
AB  - Polyfluorinated telomer alcohols and sulfonamides are classes of compounds
      recently identified as precursor molecules to the perfluorinated acids detected
      in the environment. Despite the detection and quantification of these volatile
      compounds in the atmosphere, their sources remain unknown. Both classes of
      compounds are used in the synthesis of various fluorosurfactants and incorporated
      in polymeric materials used extensively in the carpet, textile, and paper
      industries. This study has identified the presence of residual unbound fluoro
      telomer alcohols (FTOHs) in varying chain lengths (C6-C14) in several
      commercially available and industrially applied polymeric and surfactant
      materials. NMeFOSE, a perfluoroalkyl sulfonamido alcohol, was also detected in a
      commercially available carpet protector product. A method was developed to remove
      these residual compounds from polymeric and surfactant materials by dispersion in
      water and stripping of the volatiles using a constant flow of air and trapping on
      XAD resin. Using gas chromatography mass spectrometry analysis, it was determined
      that the fluorinated materials examined consist of 0.04-3.8% residual alcohols on
      a fluoro alcohol to dry mass basis. These values indicate that residual alcohols,
      left unreacted and unbound from the manufacturing process of fluorinated polymers
      and surfactants, could be a significant source of the polyfluorinated telomer
      alcohols and sulfonamides released into the environment. This study suggests that
      elimination or reduction of these residual alcohols from all marketed fluorinated
      polymers and fluorosurfactants is key in reducing the prevalence of
      perfluorinated acids formed in the environment.

PMID- 16568756
TI  - Persistent organic pollutants in the equatorial atmosphere over the open Indian
      Ocean.
AB  - Twelve air samples collected over the Indian Ocean by a high volume air sampler
      between August 2004 and August 2005 were analyzed for selected polychlorinated
      biphenyl (PCB) congeners and organochlorine pesticides. The region of the Indian
      Ocean and adjacent countries is likely to be acting as a source of selected POPs
      to the global environment. Data were compared with those reported for the last 30
      years to examine historical trends of selected persistent organic pollutants
      (POPs) over the Indian Ocean. Compound concentrations were influenced by the
      proximity to land and air mass origins. Higher concentrations of atmospheric
      sigmaPCBs (50-114 pg m(-3)) were found on the remote islands of Chagos
      Archipelago and Gan, Maldives, and in the proximity of Jakarta, Indonesia, and
      Singapore. Military activities and unregulated waste combustion were identified
      as possible sources for atmospheric PCB contaminations at the more remote areas.
      The highest concentrations of organochlorine pesticides were found adjacent to
      the coastline of Sumatra and Singapore, where sigmaDDTs
      (dichlorodiphenyltrichloroethane) and sigmaHCHs (hexacyclohexanes) were as high
      as 30 and 100 pg m(-3), respectively. A comparison study for the last 30 years
      over six regions of the Indian Ocean showed that the concentrations of
      organochlorine pesticides have declined significantly, by a magnitude of two,
      since the mid 1970s, but were highest at the beginning of the 1990s. The time
      trend of PCB contamination in the atmosphere over the Indian Ocean is less
      apparent. The decline of atmospheric POPs over the Indian Ocean may be due to
      international regulation of the use of these compounds.

PMID- 16568757
TI  - Congener-specific tissue distribution and hepatic sequestration of PCDD/Fs in
      wild herring gulls from Bohai Bay, North China: comparison to coplanar PCBs.
AB  - Tissue distribution is an important property of pharmacokinetic behaviors of
      dioxins to provide information for risk assessment to wild avian species. In this
      study, concentrations of polychlorinated dibenzo-p-dioxins (PCDDs),
      polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls
      (coplanar PCBs) were determined in muscle, liver, spleen, kidney, brain, and
      adipose of wild herring gulls collected from Bohai Bay, North China. Tissue
      distribution results showed preferential accumulation of PCDD/Fs in liver and of
      co-PCBs in adipose. The congener patterns of coplanar PCBs were constant in
      different tissues, but the congener patterns for PCDD/F were tissue-specific. The
      liver/adipose concentration ratios for PCDD/ Fs were found to increase
      statistically significantly with log K(ow), providing the quantitative
      relationship of structure-activity for hepatic sequestration of PCDD/Fs for the
      first time. Furthermore, this relationship was compared with those developed on
      the basis of previous results reported in the literature showing that the wild
      herring gulls in Bohai Bay are still in the exposure period.

PMID- 16568758
TI  - Mechanism and kinetics of cyanogen chloride formation from the chlorination of
      glycine.
AB  - Glycine is an important precursor of cyanogen chloride (CNCl)--a disinfection
      byproduct (DBP) found in chlorinated drinking water. To model CNCl formation from
      glycine during chlorination, the mechanism and kinetics of the reaction between
      glycine and free chlorine were investigated. Kinetic experiments indicated that
      CNCI formation was limited by either the decay rates of N,N-dichloroglycine or a
      proposed intermediate, N-chloroiminocarboxylate, CIN=CHCO2-. Only the anionic
      form of N,N-dichloroglycine, NCl2CH2CO2-, however, decays to form CNCl, while the
      protonated neutral species forms N-chloromethylimine. At pH > 6, glycine-nitrogen
      is stoichiometrically converted to CNCI, while conversion decreases at lower pH
      due to the formation of N-chloromethylimine. Under conditions relevant to
      drinking water treatment, i.e., at pH 6 to 8 and with free chlorine in excess, a
      simplified rate expression for the concentration of glycine-nitrogen converted to
      CNCl, [CNCl]f, applies: dt/d[CNCl]f = k2*[Cl2-Gly](T,o)exp(-k2*t) where [Cl2
      Gly]T,o is the initial concentration of total N,N-dichloroglycine, k2* is the
      first-order decay constant for CIN=CHCO2-, k2*(s(-1)) = 10(12)(+/-4) exp(-1.0(+/
      0.3) x 10(4)/T), and T is the absolute temperature in K. Kinetic expressions for
      d[CNCl]/dt when free chlorine is in excess, however, must also account for the
      significant decay of CNCl by hypochlorite-catalyzed hydrolysis, which has been
      characterized in previous studies. Although CNCl formation is independent of the
      free chlorine concentration, higher chlorine concentrations promote its
      hydrolysis.

PMID- 16568759
TI  - Cyanogen chloride precursor analysis in chlorinated river water.
AB  - Amino acids have been cited as potential precursors of the disinfection byproduct
      cyanogen chloride in chlorinated drinking water. Screening experiments with 17
      amino acids were performed in this study to comprehensively identify important
      CNCl precursors. Among this set, only glycine was found to yield detectable CNCl
      (i.e., > 0.6% yields). Additional experiments were conducted to estimate the
      relative significance of glycine as a CNCI precursor in water samples collected
      from the Huron River, Michigan, by concurrently characterizing the amino acid
      content and monitoring CNCI yields after chlorination. Chlorine was added at
      slightly less than the sample breakpoint dose to optimize CNCl formation and
      stability in the samples. On the basis of previous determinations that glycine
      nitrogen is stoichiometrically converted to CNCI-N at pH > 6, it was estimated
      that glycine may account for 42-45% of the CNCI formed in the river water samples
      (pH 8.2). The kinetic profile of CNCl formation in the sample, with a half-life
      of about 20 min, indicated that both rapid and slower formation pathways were
      important. Glycine formation of CNCl, with a half-life of 4 min, is likely to
      contribute significantly to the rapidly formed CNCI, while unidentified
      precursors must accountfor the slower pathway. Non-glycine-derived CNCl
      precursors in this water source were further examined to determine if they were
      largely proteinaceous in character using a technique known as immobilized metal
      ion affinity chromatography (IMAC). These experiments demonstrated that copper
      loaded IMAC resins were much more effective in removing glycine than other CNCI
      precursor compounds in the sample matrix. The unidentified CNCI precursor
      components, therefore, are not likely to be proteinaceous and are more likely to
      be associated with the fulvic/humic fraction of organic matter.

PMID- 16568760
TI  - Influence of copper loading and surface coverage on the reactivity of granular
      iron toward 1,1,1-trichloroethane.
AB  - Although iron-based bimetallic reductants offer promise in treating
      organohalides, the influence of additive mass loading and two-dimensional surface
      coverage on reductant reactivity has not been fully elucidated. In this study we
      examine 1,1,1-trichloroethane reduction by Cu/Fe bimetals as a function of Cu
      loading and surface coverage. Information from a suite of complementary
      techniques (X-ray photoelectron spectroscopy, Auger electron spectroscopy, and
      cross-sectional energy-dispersive X-ray spectroscopy) indicates that displacement
      plating produces a heterogeneous metallic copper overlayer on iron. The
      dependence of pseudo-first-order rate constants (k(obs) values) for 1,1,1
      trichloroethane reduction on Cu loading exhibits two distinct regimes. At Cu
      loadings less than 1 monolayer equivalent (approximately 10 micromol Cu/g Fe), a
      pronounced increase in k(obs) is associated with a corresponding increase in the
      two-dimensional surface coverage of Cu. A weaker dependence of k(obs) on Cu mass
      is exhibited at loadings in excess of 1 monolayer equivalent, which we ascribe to
      an increase in the volume of the metallic overlayer. The observed relationship
      between k(oba) and loading suggests that 1,1,1-trichloroethane reduction occurs
      on the Cu surface rather than at the interface between the Cu overlayer and the
      iron substrate.

PMID- 16568761
TI  - Does metamorphosis increase the susceptibility of frogs to highly hydrophobic
      contaminants?
AB  - The purpose of this study was to determine whether the process of metamorphosis
      in amphibians increases the chemical activity of hydrophobic contaminants such as
      polychlorinated biphenyls (PCBs). We conducted an experiment in which green frog
      tadpoles were orally dosed with a PCB mixture; then placed into clean water to
      eliminate the chemicals as metamorphosis occurred. On several sampling dates
      before and during metamorphosis, organisms were sacrificed and analyzed to
      determine lipid contents and concentrations of individual PCB congeners. The
      majority of the PCBs studied in this experiment showed increases in chemical
      activity (fugacity) as a result of the physical changes that occurred during
      amphibian metamorphosis. A positive relationship was observed between PCB
      hydrophobicity and the magnitude of the fugacity increase. We determined that the
      fugacity of a persistent PCB congener will increase during green frog
      metamorphosis if its log K(ow) value is greater than 5.85. The fugacity of some
      of the more highly hydrophobic PCBs increased during metamorphosis by up to a
      factor of 4. Because of the rapid increases in chemical activity that were
      observed during metamorphosis, we conclude that toxicity tests involving
      hydrophobic organic contaminants should be conducted not only on tadpoles or
      adult frogs, but also on metamorphosing amphibians.

PMID- 16568762
TI  - Fate of prions in soil: adsorption and extraction by electroelution of
      recombinant ovine prion protein from montmorillonite and natural soils.
AB  - Prions, the infectious agents thought to be responsible for transmissible
      spongiform encephalopathies, may contaminate soils and have been reported to
      persist there for years. We have studied the adsorption and desorption of a model
      recombinant prion protein on montmorillonite and natural soil samples in order to
      elucidate mechanisms of prion retention in soils. Clay minerals, such as
      montmorillonite, are known to be strong adsorbents for organic molecules,
      including proteins. Montmorillonite was found to have a large and selective
      adsorption capacity for both the normal and the aggregated prion protein.
      Adsorption occurred mainly via the N-terminal domain of the protein. Incubation
      with standard buffers and detergents did not desorb the full length protein from
      montmorillonite, emphasizing the largely irreversible trapping of prion protein
      by this soil constituent. An original electroelution method was developed to
      extract prion protein from both montmorillonite and natural soil samples,
      allowing quantification when coupled with rapid prion detection tests. This easy
      to-perform method produced concentrated prion protein extracts and allowed
      detection of protein at levels as low as 0.2 ppb in natural soils.

PMID- 16568763
TI  - Oxidation of the cyanobacterial hepatotoxin microcystin-LR by chlorine dioxide:
      influence of natural organic matter.
AB  - Cyanobacteria (blue-green algae) are known producers of cytotoxic, hepatotoxic,
      and neurotoxic compounds with severe acute and chronic effects on vertebrates.
      Successful removal of these toxins in drinking water treatment is therefore of
      importance for public health. In the present work the oxidation of the
      cyanobacterial hepatotoxin microcystin-LR (MC-LR) by chlorine dioxide (ClO2) was
      studied at natural microcystin concentrations (10 microg L(-1)) and normal ClO2
      dosages (1 mg L(-1)) in the absence and presence of natural organic matter (NOM).
      ClO2 was found to be rapidly consumed by fulvic and humic acids, leaving less
      residual ClO2 to oxidize MC-LR. Predicted decrease rates in MC-LR concentration
      correlated highly with experimental data both in pure water and in the presence
      of NOM. Rate constants determined at high ClO2 and MC-LR concentrations in pure
      water could be used to predict the oxidation of MC-LR at natural concentrations.
      Toxicity tests with a protein phosphatase inhibition assay on reaction solutions
      and high-performance liquid chromatography fractions revealed that PP1 enzyme
      inhibition emerged only from intact MC-LR, while the oxidation products,
      dihydroxy isomers of MC-LR, were nontoxic even at unnaturally high
      concentrations.

PMID- 16568765
TI  - Aggregation kinetics of alginate-coated hematite nanoparticles in monovalent and
      divalent electrolytes.
AB  - The early stage aggregation kinetics of bare and alginate-coated hematite
      nanoparticles are acquired through time-resolved dynamic light scattering (DLS).
      Varying concentrations of monovalent (NaCl) and divalent (MgCl2 and CaCl2)
      electrolytes are employed to induce aggregation. In the presence of NaCl and
      MgCl2, the alginate-coated hematite nanoparticles undergo aggregation through
      electrostatic destabilization as described by the classic Derjaguin-Landau-Verwey
      Overbeek (DLVO) theory. This is ascertained through examination of the favorable
      and unfavorable regimes of the stability curves depicting the attachment
      efficiency as a function of salt concentration. Additional evidence may be found
      in the aggregation kinetics of alginate-coated particles, which, under favorable
      aggregation conditions, are reasonably close to that of bare hematite
      nanoparticles. However, in the presence of CaCl2, the aggregate growth rate of
      alginate-coated hematite nanoparticles is much higher than that which
      conventional diffusive aggregation predicts. Dispersed hematite primary particles
      and lower-order aggregates enmeshed within extended alginate gel networks were
      observed under transmission electron microscope (TEM). The proposed mechanism for
      enhanced aggregation suggests an apparent increase in the collision radii of
      alginate-coated hematite nanoparticles through alginate gel network formation
      from the particle surface. Additionally, cross-linking between unadsorbed
      (suspended) alginate macromolecules may form bridges between hematite-alginate
      gel clusters. It is further established that the presence of background
      electrolyte NaCl in solution is detrimental to the calcium-induced enhanced
      aggregation.

PMID- 16568764
TI  - Physical structures of lipid layers on pyrite.
AB  - The physical structures of lipid layers on pyrite (FeS2), a ubiquitous sulfide
      mineral, were studied in air and in water by atomic force microscopy (AFM). Egg
      PC, a phospholipid that forms bilayer structures on atomically flat substrates,
      was investigated, and our experimental observations show that this lipid formed
      bilayers on an atomically rough pyrite surface, as inferred by a measured layer
      thickness of 5.0 +/- 0.2 nm. The surface coverage of the lipid coating increased
      from approximately 15% to 80% when the concentration of the lipid suspension was
      increased from 0.014 to 0.15 mM. Although further increases up to 1.5 mM resulted
      in an incremental increase in surface coverage of only 5%, multilayer structures
      of 20- to 40-nm height formed on top of the first bilayer. The findings provide a
      structural explanation for the results of earlier kinetic studies showing that
      the presence of the lipid decreases the rate of pyrite oxidation in air and in
      water. Lipid coatings applied to iron-sulfide bearing minerals are a possible
      approach to preventing oxidation and acidification and thereby mitigating
      environmental damage that can result from acid mine drainage.

PMID- 16568766
TI  - Adsorption kinetics of platinum group elements in river water.
AB  - The uptake of platinum group elements (PGE) by different preparations of
      estuarine sediment suspended in filtered river water has been examined. For a
      given PGE, adsorption time courses to untreated sediment and to sediment whose
      hydrous metal oxides or organic matter had been removed by appropriate chemical
      treatments were similar. Adsorption of Rh(lll) and Pt(IV) proceeded via a first
      order reversible reaction. For Rh, forward rate constants were 1 order of
      magnitude greater than reverse rate constants, but for Pt, forward and reverse
      constants were comparable. Respective system response times, required to attain
      63% of the new equilibrium, ranged from about 10 to 30 h and 2 to 20 h. In
      contrast, rapid, initial uptake of Pd(ll) was succeeded, in most instances, by a
      protracted period of desorption, requiring a more complex mechanistic
      interpretation. In all cases, adsorption was reduced following a period of PGE
      equilibration with filtered river water, suggesting that complexation with
      natural organic ligands exerts a significant control on the adsorption process
      by, for example, stabilizing PGE in solution. Exchangeability of adsorbed PGE,
      evaluated by ammonium acetate extraction, decreased in the order Pd > Pt > Rh, in
      qualitative agreement with the proposed or modeled adsorption mechanisms.
      Experimental results, together with independent assessments of PGE mobility from
      secondary sources (e.g. road dust), indicate that Pd has the greatest potential
      for long-range transport and bioaccumulation in the aquatic environment.

PMID- 16568767
TI  - Community structure, abundance, and in situ activity of nitrifying bacteria in
      river sediments as determined by the combined use of molecular techniques and
      microelectrodes.
AB  - The community structure, spatial distributions, and in situ activity of ammonia
      oxidizing bacteria (AOB) representing the Betaproteobacteria and nitrite
      oxidizing bacteria (NOB) representing the genus Nitrospira in three different
      river sediments with different pollution sources and levels along the Niida
      River, Hachinohe, Japan, were investigated by the combined use of 16S rRNA gene
      cloning analysis, real-time quantitative polymerase chain reaction (RTQ-PCR)
      assays, and microelectrodes. The goal of this research was to evaluate the
      contribution of nitrifying activity in the sediment to the overall nitrogen
      elimination rate in this river. The 16S rRNA gene-cloning analysis revealed that
      the community structures of AOB and Nitrospira-like NOB are present in three
      sediments. On the basis of the results of 16S rRNA gene-cloning analysis, the RTQ
      PCR assay using a TaqMan probe was developed and optimized for the quantification
      of the Nitrospira-like NOB. In the sediments, AOB specific 16S rRNA genes were
      detected in the range of 10(6) to 10(7) copies/cm3 and evenly distributed over
      the sampled sediment depth (0-5 mm), whereas the Nitrospira-like NOB 16S rRNA
      gene copy numbers per cm3 were 1-2 orders of magnitude higher than the AOB copy
      numbers. Under light conditions, intensive oxygenic photosynthesis occurred in
      the surface and increased the maximal O2 concentration and O2 penetration depth
      in all sediments. This concomitantly stimulated nitrifying bacteria present in
      diurnally anoxic deeper zones and expanded nitrification zones, which
      consequently increased the total NH4+ consumption rate in the sediment (i.e.,
      total NH4+ flux into the sediment). The results suggested that the in situ
      nitrifying activity was restricted mainly to the surface 2 mm of the sediment and
      linked with photosynthetic activity, which obviously plays an important role in
      nitrogen elimination in this river.

PMID- 16568768
TI  - Mercury methylation in the epilithon of boreal shield aquatic ecosystems.
AB  - Methylation rates by periphyton growing on the rocky shore of a remote boreal
      shield lake were measured over diurnal cycles at temperatures representative of
      summer and fall conditions. The measurements were carried out in vitro with
      natural communities grown on artificial Teflon substrates submerged along the
      lake's shore for 1-2 years. At temperatures above 20 degrees C, epilithon Hg
      methylation rates were fast and reached a steady state within 12 h upon exposure
      to 2 ng L(-1) of inorganic mercury. A variety of inhibitors were used to identify
      which microorganisms in the epilithic biofilm are responsible for the
      methylation. The addition of molybdate, which is believed to suppress the
      activity of sulfate-reducing bacteria, decreased methylmercury production rates
      by 60% in both light and dark experiments. The prokaryote inhibitor
      chloramphenicol reduced the methylation rate by 40% only during dark periods
      whereas an algal inhibitor (DCMU), which suppresses photosynthesis, decreased the
      methylation rate by 60% during light periods. Results of this study reveal that
      epilithon communities may be a significant source of MeHg to higher aquatic
      organisms in lakes and that the integrity of the epilithic biofilm is important
      for its ability to methylate Hg.

PMID- 16568769
TI  - Virus retention and transport in chemically heterogeneous porous media under
      saturated and unsaturated flow conditions.
AB  - Retention and transport of colloids and microorganisms are complex processes,
      especially in the vadose zone due to the more complicated water flow regime and
      additional interfacial reactions involved. In this study, we examined the
      retention and transport behavior of two bacteriophages, MS-2 and phiX174, in
      homogeneous and chemically heterogeneous media under variably saturated
      conditions. Column experiments with glass beads (treated to have either
      hydrophilic or hydrophobic surface properties) were conducted using a phosphate
      buffered saline solution at different pore water ionic strengths ranging from
      0.025 to 0.163 M. In columns packed with 100% hydrophilic glass beads, retention
      of the viruses increased with decreasing water content and increasing ionic
      strength, a result similar to those reported in the literature. However, greater
      retention of both MS-2 and phiX174 was observed in saturated columns than in
      unsaturated columns packed with a 1:1 mixture of hydrophilic and hydrophobic
      glass beads, especially at high ionic strengths. This result contradicts the
      common belief that viruses (and colloids in general) are subject to greater
      removal in unsaturated media. Our study suggests that while the mechanisms
      controlling colloid interfacial interactions (i.e., attachment on solid-water and
      air-water interfaces and film straining) on the pore scale are relevant,
      nonuniform wetting conditions due to heterogeneous grain surface hydrophobicity
      can strongly influence water flow and phase interconnection. Under these
      conditions, hydrodynamic effects on the mesopore scale will dominate pore-scale
      interfacial reactions in controlling the extent of colloid retention and movement
      in unsaturated media.

PMID- 16568770
TI  - Speciation and quantitative mapping of metal species in microbial biofilms using
      scanning transmission X-ray microscopy.
AB  - A scanning transmission X-ray microscope illuminated with synchrotron light was
      used to investigate the speciation and spatial distributions of metals in a
      microbial biofilm cultivated from river water. Metal 2p absorption edge signals
      were used to provide metal speciation (through shapes of the absorption spectra)
      and quantitative spatial distributions of the metal species. This paper presents
      sample data and describes methods for extracting quantitative maps of metal
      species from image sequences recorded in the region of the metal 2p edges.
      Comparisons were made with biochemical characterization of the same region using
      images recorded at the C 1s and O 1s edges. The method is applied to detailed
      quantitative analysis of ferrous and ferric iron in a river biofilm, in concert
      with mapping Ni(II) and Mn(II) species in the same region. The distributions of
      the metal species are discussed in the context of the biofilm structure. These
      results demonstrate that soft X-ray STXM measurements at the metal 2p absorption
      edges can be used to speciate metals and to provide quantitative spatial
      distribution maps for metal species in environmental samples with 50 nm spatial
      resolution.

PMID- 16568771
TI  - Ethylenediamine at air/liquid and air/silica interfaces: protonation versus
      hydrogen bonding investigated by sum frequency generation spectroscopy.
AB  - The adsorption process on mineral oxide surfaces is one of the most important
      factors influencing the migration and distribution of contaminants in the
      environment. Although there have been numerous studies carried out at the
      macroscopic scale, there is a lack of molecular-scale interfacial information.
      The molecular-scale information is often crucial for the determination of
      sorption mechanisms. In this study, sum frequency generation spectroscopy (SFG),
      a surface specific vibrational spectroscopy, has been employed to investigate the
      adsorption of ethylenediamine (H2N(CH2)2NH2, EDA) onto the amorphous SiO2 surface
      and EDA protonated products at air/liquid interfaces. The SFG spectra of EDA
      adsorbed on the silica surface and the singly protonated EDA solution are similar
      in both CH and NH stretching regions. These spectral similarities indicate that
      EDA molecules are strongly chemisorbed to the silica surface through the
      protonation of one EDA amine group by surface silanol OH groups, thereby forming
      a (H2N(CH2)2NH3)+(O-Si[triple bond])- surface complex. The SFG results also
      indicate that the surface acidity of the silanol OH groups (pKa (HOSi[triple
      bond])) is between the two pKa values of EDA (in the range of 7.56-10.71) at the
      air/silica interface.

PMID- 16568772
TI  - Estimating the impact of high-production-volume chemicals on remote ecosystems by
      toxic pressure calculation.
AB  - Although many chemicals are in use, the environmental impacts of only a few have
      been established, usually on per-chemical basis. Uncertainty remains about the
      overall impact of chemicals. This paper estimates combined toxic pressure on
      coastal North Sea ecosystems from 343 high-production-volume chemicals used
      within the catchment of rivers Rhine, Meuse, and Scheldt. Multimedia fate
      modeling and species sensitivity distribution-based effects estimation are
      applied. Calculations start from production volumes and emission rates and use
      physicochemical substance properties and aquatic ecotoxicity data. Parameter
      uncertainty is addressed by Monte Carlo simulations. Results suggest that the
      procedure is technically feasible. Combined toxic pressure of all 343 chemicals
      in coastal North Seawater is 0.025 (2.5% of the species are exposed to
      concentration levels above EC50 values), with a wide confidence interval of
      nearly 0-1. This uncertainty appears to be largely due to uncertainties in
      interspecies variances of aquatic toxicities and, to a lesser extent, to
      uncertainties in emissions and degradation rates. Due to these uncertainties, the
      results support gross ranking of chemicals in categories: negligible and possibly
      relevant contributions only. With 95% confidence, 283 of the 343 chemicals (83%)
      contribute negligibly (less than 0.1%) to overall toxic pressure, and only 60
      (17%) need further consideration.

PMID- 16568773
TI  - A bioenergetic biomagnification model for the animal kingdom.
AB  - Species vary greatly in the degree to which they accumulate dietary contaminants.
      Bioenergetic processes play a key role in chemical uptake and elimination, and
      interspecific variation in bioaccumulation can be attributed in large part to
      variation in how species feed, digest, and allocate energy. We present a
      quantitative treatment of this relationship for the entire animal kingdom. We
      derive a model to predict the biomagnification factor for nonmetabolizable,
      slowly eliminated chemicals, BMF(max). We test the model with observed
      biomagnification factors and independently derived bioenergetic parameters for a
      diverse suite of species, including herbivores and carnivores, heterotherms and
      homeotherms, vertebrates and invertebrates, adults and juveniles,
      domestic/laboratory animals and wild individuals from freshwater, marine, and
      terrestrial environments. The model successfully predicts species-specific
      BMF(max) values across this range of taxa, with values ranging from less than 1
      in caterpillars to nearly 100 in some carnivores. In addition, we make novel
      predictions of BMF(max) for several taxa for which no measured bioaccumulation
      data are available. Our analysis provides new insights into the role of ecology
      in chemical dynamics across the animal kingdom, providing a general framework for
      understanding how characteristics of an organism and its ecological context
      influence the degree to which that organism accumulates chemicals present in its
      diet.

PMID- 16568774
TI  - Does the Rayleigh equation apply to evaluate field isotope data in contaminant
      hydrogeology?
AB  - Stable isotope data have been increasingly used to assess in situ biodegradation
      of organic contaminants in groundwater. The data are usually evaluated using the
      Rayleigh equation to evaluate whether isotope data follow a Rayleigh trend, to
      calculate the extent of contaminant biodegradation, or to estimate first-order
      rate constants. However, the Rayleigh equation was developed for homogeneous
      systems while in the subsurface, contaminants can migrate at different velocities
      due to physical heterogeneity. This paper presents a method to quantify the
      systematic effect that is introduced by applying the Rayleigh equation to field
      isotope data. For this purpose, the travel time distribution between source and
      sampling point is characterized by an analytical solution to the advection
      dispersion equation. The systematic effect was evaluated as a function of the
      magnitude of physical heterogeneity, geometry of the contaminant plume, and
      degree of biodegradation. Results revealed that the systematic effect always
      leads to an underestimation of the actual values of isotope enrichment factors,
      the extent of biodegradation, or first-order rate constants, especially in the
      dispersion-dominant region representing a higher degree of physical
      heterogeneity. A substantial systematic effect occurs especially for the
      quantification of first-order rate constants (up to 50% underestimation of actual
      rate) while it is relatively small for quantification of the extent of
      biodegradation (< 5% underestimation of actual degree of biodegradation). The
      magnitude of the systematic effect is in the same range as the uncertainty due to
      uncertainty of the analytical data, of the isotope enrichment factor, and the
      average travel time.

PMID- 16568775
TI  - Measurement of un-ionized ammonia in complex mixtures.
AB  - The toxicity of un-ionized ammonia, NH3 (aq), in anaerobic digestion of high
      nitrogen wastes has been researched extensively. Previous estimates of NH3 (aq)
      concentration have relied on a simple speciation approach, based only on the acid
      dissociation constant and the sample pH and total ammonia concentration. The
      distinction between concentration and chemical activity has generally not been
      made, despite the potential for resulting errors in the calculation of NH3 (aq)
      concentration, and the greater applicability of activity to toxicity work. The
      currently accepted approach for estimating NH3 (aq) concentration is based on
      assumptions that are not valid in digested animal manure or other concentrated
      wastes. This work presents an approach for directly measuring NH3 (aq) activity
      in complex mixtures using gaseous/aqueous equilibrium across microporous tubing.
      Application of this approach to anaerobic digester samples confirms that the
      currently accepted approach is not accurate; it overestimated NH3 (aq) activity
      in unaltered samples by 45-200%. Previous work on the toxicity of ammonia to
      methanogenesis has probably overestimated the tolerance of consortia to NH3 (aq),
      due to overestimation of concentrations. The method introduced here is expected
      to be useful in a range of research on ammonia toxicity and volatilization.

PMID- 16568776
TI  - Application of gold catalyst for mercury oxidation by chlorine.
AB  - This paper discusses a recent study of mercury catalytic oxidation by
      chlorinating reagents. Gold was chosen as the catalyst because of its reluctance
      to chemisorb some gases such as O2, NO, H2O, and SO2. This property, as
      demonstrated in this study, is instrumental to mercury oxidation by circumventing
      some undesired inhibitory reactions such as OH + NO + M --> HONO + M and OH + SO2
      + M --> HOSO2 + M, which were recognized under homogeneous situations at high
      temperatures. In comparison to Cl2, HCl showed weak oxidizing capability but
      appreciable inhibition in mercury oxidation by Cl2, probably through the
      competition of active sites with Cl2. Overall, the mercury catalytic oxidation by
      Cl2 on gold catalyst surfaces was viable, reaching 40-60% in this study under
      temperatures of 448-498 K, where the thermal decomposition of formed Hg2+ was
      effectively avoided.

PMID- 16568777
TI  - UV reactor performance modeling by Eulerian and Lagrangian methods.
AB  - A study was performed to investigate the influence of hydrodynamics on the
      performance of ultraviolet (UV) reactors. Two general UV disinfection models were
      developed by integrating fluence rate models and inactivation kinetics within a
      commercial computational fluid dynamics (CFD) software package to predict reactor
      performances. Both a particle tracking (Lagrangian) random walk model and a
      volumetric reaction rate based (Eulerian) model were implemented. Simulations
      were performed for two characteristic annular single-lamp UV reactor
      configurations, with inlets concentric (L-shape) and normal (U-shape) to the
      reactor axis. Two fluence rate models, the infinite line source assumption and
      the finite line or multiple point source summation (MPSS), were used. First-order
      inactivation kinetics was assumed for disinfection, with rate constants from MS2
      bacteriophage assays. The simulation results provided detailed information on the
      velocity profiles, reaction rates, range of absorbed dose, and areas of short
      circuiting of the UV reactors. Model predictions based on both the Lagrangian
      dose distribution and Eulerian concentration distribution were in good agreement
      with each other at high flow rates but showed some discrepancies at lower flow
      rates. Experimental verification of the general models was performed by
      simulating the disinfection performance of an industrial prototype UV reactor.
      Results from both integration approaches were shown to be in good agreement with
      the provided biodosimetry data.

PMID- 16568778
TI  - Photocatalytic activity for degradation of nitrogen oxides over visible light
      responsive titania-based photocatalysts.
AB  - This study investigates photocatalytic degradation of nitrogen oxides overtitania
      based photocatalysts illuminated by ultraviolet and visible light. The TiO2
      photocatalyst was synthesized in a sol-gel process using titanium butoxide as the
      precursor. After calcination between 150 and 300 degrees C, the synthesized TiO2
      responded strongly to visible light photocatalytically degrading NO(x), probably
      because of the existence of carbonaceous species that act as sensitizers. The
      optimum calcination temperature was found to be around 200 degrees C.
      Additionally, platinum ion-doped TiO2 was prepared by impregnation using
      Pt(NH3)4(NO3)2 as a dopant, which improved the photocatalytic activity that
      degraded NO(x) in the visible light region. The Pt ion was doped in oxide form at
      the surface of TiO2 and was expected to be responsible for sensitization. At an
      optimum calcination temperature of around 200 degrees C, the Pt ion-doped TiO2
      exhibited higher activity in the further oxidation of NO2 to NO3- clearly
      reducing NO2 selectivity. The TiO2 catalysts chemically prepared by either the
      sol-gel process or impregnation exhibited stronger activity than conventional
      TiO2 when illuminated under a fluorescent lamp. Rinsing with water was
      responsible for the restored reactivity of prepared TiO2 catalysts for NO(x)
      degradation.

PMID- 16568779
TI  - Modeling of experimental treatment of acetaldehyde-laden air and phenol
      containing water using corona discharge technique.
AB  - Acetaldehyde-laden air and phenol-contaminated water were experimentally treated
      using corona discharge reactions and gas absorption in a single water-film
      column. Mathematical modeling of the combined treatment was developed in this
      work. Efficient removal of the gaseous acetaldehyde was achieved while the corona
      discharge reactions produced short-lived species such as O and O- as well as
      ozone. Direct contact of the radicals and ions with water was known to produce
      aqueous OH radical, which contributes to the decomposition of organic
      contaminants: phenol, absorbed acetaldehyde, and intermediate byproducts in the
      water. The influence of initial phenol concentration ranging from 15 to 50 mg L(
      1) and that of influent acetaldehyde ranging from 0 to 200 ppm were
      experimentally investigated and used to build the math model. The maximum
      energetic efficiency of TOC, phenol, and acetaldehyde were obtained at 25.6 x 10(
      9) mol carbon J(-1), 25.0 x 10(-9) mol phenol J(-1), and 2.0 x 10(-9) mol
      acetaldehyde J(-1), respectively. The predictions for the decomposition of
      acetaldehyde, phenol, and their intermediates were found to be in good agreement
      with the experimental results.

PMID- 16568780
TI  - Modeling of copper sorption onto GFH and design of full-scale GFH adsorbers.
AB  - During rain events, copper wash-off occurring from copper roofs results in
      environmental hazards. In this study, columns filled with granulated ferric
      hydroxide (GFH) were used to treat copper-containing roof runoff. It was shown
      that copper could be removed to a high extent. A model was developed to describe
      this removal process. The model was based on the Two Region Model (TRM), extended
      with an additional diffusion zone. The extended model was able to describe the
      copper removal in long-term experiments (up to 125 days) with variable flow rates
      reflecting realistic runoff events. The four parameters of the model were
      estimated based on data gained with specific column experiments according to
      maximum sensitivity for each parameter. After model validation, the parameter set
      was used for the design of full-scale adsorbers. These full-scale adsorbers show
      high removal rates during extended periods of time.

PMID- 16568781
TI  - Removal of arsenite and arsenate using hydrous ferric oxide incorporated into
      naturally occurring porous diatomite.
AB  - In this study, a simplified and effective method was tried to immobilize iron
      oxide onto a naturally occurring porous diatomite. Experimental resultsfor
      several physicochemical properties and arsenic edges revealed that iron oxide
      incorporated into diatomite was amorphous hydrous ferric oxide (HFO). Sorption
      trends of Fe (25%)-diatomite for both arsenite and arsenate were similar to those
      of HFO, reported by Dixit and Hering (Environ. Sci. Technol. 2003, 37, 4182
      4189). The pH at which arsenite and arsenate are equally sorbed was 7.5, which
      corresponds to the value reported for HFO. Judging from the number of moles of
      iron incorporated into diatomite, the arsenic sorption capacities of Fe (25%)
      diatomite were comparable to or higher than those of the reference HFO.
      Furthermore, the surface complexation modeling showed that the constants of
      [triple bond]SHAsO4- or [triple bond]SAsO4(2-) species for Fe (25%)-diatomite
      were larger than those reference values for HFO or goethite. Larger differences
      in constants of arsenate surface species might be attributed to aluminum hydroxyl
      ([triple bond]Al-OH) groups that can work better for arsenate removal. The pH
      controlled differential column batch reactor (DCBR) and small-scale column tests
      demonstrated that Fe (25%)-diatomite had high sorption speeds and high sorption
      capacities compared to those of a conventional sorbent (AAFS-50) that is known to
      be the first preference for arsenic removal performance in Bangladesh. These
      results could be explained by the fact that Fe (25%)-diatomite contained well
      dispersed HFO having a great affinity for arsenic species and well-developed
      macropores as shown by scanning electron microscopy (SEM) and pore size
      distribution (PSD) analyses.

PMID- 16568782
TI  - Rates of oxidative coupling of humic phenolic monomers catalyzed by a biomimetic
      iron-porphyrin.
AB  - A synthetic water-soluble meso-tetra(2,6-dichloro-3-sulfonatophenyl)porphyrinate
      of iron(lll) chloride (FeP) was used as biomimetic catalyst in the oxidative
      coupling of three monomeric phenols (catechol, caffeic, and p-coumaric acids),
      which are common constituents of natural humic substances. The extent of
      oxidation induced by the FeP catalyst in solutions of phenolic monomers was
      followed in the presence of an oxygen donor such as hydrogen peroxide or
      dissolved oxygen under daylight radiation. Both UV- and fluorescence-detected
      liquid chromatograms indicated that primary oxidation products had a larger
      electronic conjugation and molecular mass than the original phenols, thereby
      suggesting that the biomimetic oxidative catalysis produced covalently linked
      phenylene and oxyphenylene oligomers. However, the polyphenolic products were
      further oxidized in the progress of the catalytic reaction to possible
      undetectable aliphatic acids or even to complete mineralization. Rate constants
      describing the initial reaction period were larger for the catalyzed oxidation
      with hydrogen peroxide than those for the noncatalyzed control solutions under
      autoxidation or hydrogen peroxide treatment. However, the rate constants measured
      for the phenol solutions treated with just the FeP catalyst showed that the
      presence of dissolved oxygen and the action of the daylight radiation were
      sufficient to significantly increase the reaction rate in respect to control
      solutions. These results confirmed previous findings, showing that humic
      materials may undergo oxidative coupling catalyzed by metal-porphyrins in the
      presence of either an oxygen donor or, simply, dissolved molecular oxygen under
      daylight. The increase of molecular mass of natural humic and polyphenolic
      substances by this biomimetic technology may have useful applications in
      environmental chemistry.

PMID- 16568783
TI  - Development of engineered natural organic sorbents for environmental
      applications. 1. Materials, approaches, and characterizations.
AB  - A technology for effecting diagenesis-like transformations in young natural
      organic matter (NOM) derived from common plant materials is described. Thirteen
      such materials were processed in liquid-phase water at superheated
      temperature/pressure conditions. In all cases significant changes in the physical
      and chemical properties of the raw NOM source materials occurred. Their carbon
      and nitrogen contents increased, their hydrogen and oxygen contents decreased,
      their surface areas initially increased dramatically, then sharply decreased, and
      their bulk densities and equilibrated aqueous phase pH values increased as
      functions of increasing temperature and pressure. Spectroscopic analyses
      confirmed marked changes in the molecular structures of the NOMs resulting from
      superheated water processing; e.g., fractions of alkyl and aromatic carbons
      increased while oxygen-associated functional organic carbon decreased. These
      changes in elemental composition and molecular structure indicate that the
      organic fractions of the raw materials became less polar, increasingly condensed,
      and more aromatic as a result of the reactions induced by superheated water
      processing, the changes correlating directly with the temperature/ pressure
      conditions employed. The results presented confirm that the long-term
      biogeochemical processes that in nature effect geologically slow advances in the
      chemical states of organic carbon can be simulated and markedly accelerated by
      superheated water processing.

PMID- 16568784
TI  - Development of engineered natural organic sorbents for environmental
      applications. 2. Sorption characteristics and capacities with respect to
      phenanthrene.
AB  - The effects of superheated water processing on enhancement of phenanthrene
      sorption by various source materials of natural organic matter (NOM) were
      systematically examined. Sorption capacities and subsequent phenanthrene
      retention characteristics of all organic materials tested were markedly increased
      by superheated water processing. Temperature effects on enhancement of the
      sorption behaviors of the test materials were greater than those of processing
      time, moisture content, and the presence of mineral catalysts. Greatest
      enhancement was observed for processing at 250 degrees C for 5 h with a moisture
      content of 50%. Strong correlations of sorption capacities and isotherm
      nonlinearities with processing temperature, and with the atomic ratios of oxygen
      to carbon (O/C), aromaticity, and hydrophobicity of the processed materials were
      observed. The sorption/desorption hysteresis indices of the processed materials
      also increased linearly with processing temperatures and O/C ratios. This is
      consistent with our observations of increased condensation and aromatization of
      NOM during superheated water processing presented in the first paper of this
      series. The relationships described provide direct experimental evidence that the
      sorption-desorption properties of NOM geosorbents are closely related to their
      degree of aromatization and condensation, and the work suggests strong potential
      for production of efficient and cost-effective engineered natural organic
      sorbents for environmental applications.

PMID- 16568785
TI  - Bioreduction of selenate using a hydrogen-based membrane biofilm reactor.
AB  - A H2-based, denitrifying and sulfate-reducing membrane-biofilm reactor (MBfR) was
      shown to be effective for removing selenate (Se(VI)) from water or wastewater by
      reducing it to insoluble Se(0). When Se(VI) was first added to the MBfR, Se(VI)
      reduction--first to selenite (Se(IV)) and then mostly to Se(0)--took place
      immediately and then increased over three weeks, suggesting enrichment for
      dissimilatory selenium-reducing bacteria. Increasing the H2 pressure improved the
      Se(VI) reduction rate and total-Se removal, and lowering the influent Se(VI)
      concentration from 1000 to 260 microg Se/L increased the average Se removal to
      94%, which corresponded to an effluent Se concentration of less than 12 microg
      Se/L, a value well below the standard of 50 microg Se/L. The fact that the
      effluent suspended solids contained reduced Se suggests that Se(0) was retained
      in the biofilm, which detached to form the effluent suspended solids. A series of
      short-term experiments elaborated on how decreased influent selenate loading and
      increased H2 pressure could systematically improve the reduction of Se(VI) and
      removal of total Se. Short-term experiments also demonstrated that selenate
      reduction improved with lower influent nitrate concentration, suggesting that H2
      was more available for selenate reduction when the H2 demand for denitrification
      was smaller. Complete sulfate reduction, which occurred in parallel to nitrate
      reduction, dominated the electron-equivalent flux. Like selenate reduction, but
      unlike nitrate reduction, sulfate reduction was sensitive to H2 pressure and
      appeared to be inhibited by selenate. Finally, selenate reduction was relatively
      insensitive to pH in the range of 7.0 to 9.0. This research shows that the MBfR
      can be effective for removing Se(VI) in water or wastewater to below the 50
      microg Se/L standard.

PMID- 16568786
TI  - Economic analysis of electronic waste recycling: modeling the cost and revenue of
      a materials recovery facility in California.
AB  - The objectives of this study are to identify the various techniques used for
      treating electronic waste (e-waste) at material recovery facilities (MRFs) in the
      state of California and to investigate the costs and revenue drivers for these
      techniques. The economics of a representative e-waste MRF are evaluated by using
      technical cost modeling (TCM). MRFs are a critical element in the infrastructure
      being developed within the e-waste recycling industry. At an MRF, collected e
      waste can become marketable output products including resalable
      systems/components and recyclable materials such as plastics, metals, and glass.
      TCM has two main constituents, inputs and outputs. Inputs are process-related and
      economic variables, which are directly specified in each model. Inputs can be
      divided into two parts: inputs for cost estimation and for revenue estimation.
      Outputs are the results of modeling and consist of costs and revenues,
      distributed by unit operation, cost element, and revenue source. The results of
      the present analysis indicate that the largest cost driver for the operation of
      the defined California e-waste MRF is the materials cost (37% of total cost),
      which includes the cost to outsource the recycling of the cathode ray tubes
      (CRTs) (dollar 0.33/kg); the second largest cost driver is labor cost (28% of
      total cost without accounting for overhead). The other cost drivers are
      transportation, building, and equipment costs. The most costly unit operation is
      cathode ray tube glass recycling, and the next are sorting, collecting, and
      dismantling. The largest revenue source is the fee charged to the customer; metal
      recovery is the second largest revenue source.

PMID- 16568787
TI  - Novel photodegradable low-density polyethylene-TiO2 nanocomposite film.
AB  - A new type of photodegradable low-density polyethylene (LDPE)-TiO2 nanocomposite
      film was prepared by a melt blending technique. The photocatalytic degradation of
      the LDPE-TiO2 nanocomposites was investigated. The as-prepared films were
      characterized by scanning electron microscopy (SEM), high-temperature gel
      permeation chromatography (HT-GPC), X-ray photoelectron spectroscopy (XPS), FT-IR
      spectroscopy, and the photoinduced weight loss. The results show that the LDPE
      TiO2 nanocomposite films could be efficiently degraded under UV or sunlight
      illumination. The weight loss rate of the composite film reached 68.38%, the
      average molecular weight (Mw) of the composite film decreased 94.56%, and the
      number of average molecular weight (Mn) decreased 93.75% after UV-light
      irradiation for 400 h. FT-IR and XPS analysis indicated that the LDPE was
      oxidized during UV-light irradiation. The photocatalytic degradation mechanism of
      the films is briefly discussed.

PMID- 16568789
TI  - Improved system integration for integrated gasification combined cycle (IGCC)
      systems.
AB  - Integrated gasification combined cycle (IGCC) systems are a promising technology
      for power generation. They include an air separation unit (ASU), a gasification
      system, and a gas turbine combined cycle power block, and feature competitive
      efficiency and lower emissions compared to conventional power generation
      technology. IGCC systems are not yet in widespread commercial use and
      opportunities remain to improve system feasibility via improved process
      integration. A process simulation model was developed for IGCC systems with
      alternative types of ASU and gas turbine integration. The model is applied to
      evaluate integration schemes involving nitrogen injection, air extraction, and
      combinations of both, as well as different ASU pressure levels. The optimal
      nitrogen injection only case in combination with an elevated pressure ASU had the
      highest efficiency and power output and approximately the lowest emissions per
      unit output of all cases considered, and thus is a recommended design option. The
      optimal combination of air extraction coupled with nitrogen injection had
      slightly worse efficiency, power output, and emissions than the optimal nitrogen
      injection only case. Air extraction alone typically produced lower efficiency,
      lower power output, and higher emissions than all other cases. The recommended
      nitrogen injection only case is estimated to provide annualized cost savings
      compared to a nonintegrated design. Process simulation modeling is shown to be a
      useful tool for evaluation and screening of technology options.

PMID- 16568788
TI  - Chemicals from wastes: compost-derived humic acid-like matter as surfactant.
AB  - Compost humic acid-like (cHAL) polymeric matter (MW = 15610), isolated in 12%
      yield from food and green waste compost, exhibits very good surfactant properties
      in aqueous solution: i.e., critical micelle concentration (cmc) = 403 mg/L and
      surface tension at cmc = 36.1 mN/m. Values of cmc are confirmed also by
      conductivity and phenanthrene solubility measurements. These results, compared
      with those for other major commercial and research surfactants, propose cHAL as a
      competitive low-cost biosurfactant.

PMID- 16568790
TI  - Pyrethroid insecticides and sediment toxicity in urban creeks from California and
      Tennessee.
AB  - Pyrethroid pesticides have replaced organophosphates for many urban applications,
      including structural pest control, landscape maintenance, and residential home
      and garden use. This study was intended to determine if pyrethroids are
      detectable and widespread in diverse urban systems and if concentrations are high
      enough to cause associated aquatic toxicity. Urban creeks in California and
      Tennessee were tested on up to four occasions for pesticide residues in
      sediments, and aquatic toxicity was determined by acute toxicity tests using the
      amphipod, Hyalella azteca. In California, 12 of the 15 creeks tested were toxic
      on at least one sampling occasion, and sediment pyrethroid concentrations were
      sufficient to explain the observed toxicity in most cases. The pyrethroid
      bifenthrin, due to its high concentrations and relative toxicity as compared to
      other pyrethroids, was likely responsible for the majority of the toxicity at
      most sites. Cypermethrin, cyfluthrin, deltamethrin, and lambda-cyhalothrin also
      contributed to toxicity at some locations. The source of cypermethrin and
      deltamethrin was probably almost entirely structural pest control by professional
      applicators. Bifenthrin, cyfluthrin, and lambda-cyhalothrin may have originated
      either from professional structural pest control or from lawn and garden care by
      homeowners. None of the sediments collected from the 12 Tennessee creeks were
      toxic, and pyrethroids were rarely detectable. Regional differences between
      Tennessee and California are possibly attributable to climate, differences in
      types of residential development, and pesticide use practices.

PMID- 16568791
TI  - Spatial analysis of potential carcinogenic risks associated with ingesting
      arsenic in aquacultural tilapia (Oreochromis mossambicus) in blackfoot disease
      hyperendemic areas.
AB  - This work analyzed spatially potential carcinogenic risks associated with
      ingesting arsenic (As) contents in aquacultural tilapia (Oreochromis mossambicus)
      in coastal regions of southwestern Taiwan, where the blackfoot disease prevails.
      Sequential indicator simulation (SIS) was used to reproduce As exposure
      distributions in groundwater based on their three-dimensional variability. A
      target cancer risk (TR) associated with ingesting As in aquacultural tilapia was
      calculated to evaluate the potential risk to human health. Owing to sparse
      measured data, Monte Carlo simulation and SIS properly accounted for the
      uncertainty of assessed parameters. The probabilistic risk assessment formulated
      suitable strategies under various remedial stages. Aquacultural regions with high
      risks were mapped to elucidate the safety of groundwater use at different depths.
      Many TRs determined from the risks at the 75th and 95th percentiles exceed one
      millionth in the regions, indicating that ingesting tilapia farmed in the highly
      As-polluted regions poses potential cancer threats to human health. The 75th
      percentile of TR is considered in formulating a remedial strategy for the
      aquacultural use of groundwater in the preliminary stage. Additionally, this
      study suggests reducing the use of groundwater in aquaculture or changing the
      depths from which groundwater is withdrawn in the areas with high risks of
      cancer.

PMID- 16568792
TI  - Comment on "limited temporal variability of arsenic concentrations in 20 wells
      monitored for 3 years in Araihazar, Bangladesh".

PMID- 16568793
TI  - Comment on "limited temporal variability of arsenic concentrations in 20 wells
      monitored for 3 years in Araihazar, Bangladesh".

PMID- 16568794
TI  - Soil uptake of carbon monoxide emitted in the exhaust of a gasoline-powered
      engine.
AB  - Carbon monoxide (CO) poses dangers to both human and environmental health,
      sickening thousands of people annually in the United States and decreasing the
      capacity of the atmosphere to oxidize greenhouse gases. Globally, soil ecosystems
      with their populations of bacteria, fungi, and algae are estimated to remove 9
      36% of total CO emissions, which makes them the second largest CO sink after
      hydroxyl oxidation. Our aim was determine whether soil ecosystems could remove CO
      from an atmosphere mixed with gasoline-powered engine exhaust. Sealed microcosms
      containing no soil (NoSoil), nonvegetated soil (Soil), or vegetated soil
      (Soil+Veg), were exposed to 800, 100, and 50 ppm of CO for 1 hr. The uptake rate
      of CO was found to be higher at the 800 ppm level suggesting first-order rate
      kinetics. Soil+Veg exhibited a significantly higher CO uptake rate than either
      Soil or NoSoil (P<0.05), and Soil exhibited significantly higher uptake than
      NoSoil (P<0.05). As a free ecosystem service, the uptake of CO by soil ecosystems
      needs to be properly valued and ecologically engineered into the urban traffic
      network in a manner analogous to how wetlands, vegetated swales, and other
      ecologically based storm water treatment systems have improved urban runoff.

PMID- 16568795
TI  - Real-world vehicle emissions: A summary of the 15th coordinating research council
      on-road vehicle emissions workshop.
AB  - The Coordinating Research Council held its 15th workshop in April 2005, with
      nearly 90 presentations describing the most recent mobile source-related
      emissions research. In this paper, the authors summarize the presentations from
      researchers who are engaged in improving our understanding of the contribution of
      mobile sources to air quality. Participants in the workshop discussed emission
      models and emission inventories, results from gas- and particle-phase emissions
      studies from spark-ignition and diesel-powered vehicles (with an emphasis in this
      workshop on particle emissions), effects of fuels on emissions, evaluation of in
      use emissions control programs, and efforts to improve our capabilities in
      performing on-board emissions measurements, as well as topics for future
      research.

PMID- 16568796
TI  - Anaerobic mesophilic treatment of cattle manure in an upflow anaerobic sludge
      blanket reactor with prior pasteurization.
AB  - Different autonomous communities located in northern Spain have large populations
      of dairy cattle. In the case of Asturias, the greatest concentration of dairy
      farms is found in the areas near the coast, where the elimination of cattle
      manure by means of its use as a fertilizer may lead to environmental problems.
      The aim of the present research work was to study the anaerobic treatment of the
      liquid fraction of cattle manure at mesophilic temperature using an upflow
      anaerobic sludge blanket (UASB) reactor combined with a settler after a
      pasteurization process at 70 degrees C for 2 hr. The manure used in this study
      came from two different farms, with 40 and 200 cows, respectively. The manure
      from the smaller farm was pretreated in the laboratory by filtration through a 1
      mm mesh, and the manure from the other farm was pretreated on the farm by
      filtration through a separator screw press (0.5-mm mesh). The pasteurization
      process removed the pathogenic microorganisms lacking spores, such as
      Enterococcus, Yersinia, Pseudomonas, and coliforms, but bacterial spores are only
      reduced by this treatment, not removed. The combination of a UASB reactor and a
      settler proved to be effective for the treatment of cattle manure. In spite of
      the variation in the organic loading rate and total solids in the influent during
      the experiment, the chemical oxygen demand (COD) of the effluent from the settler
      remained relatively constant, obtaining reductions in the COD of approximately
      85%.

PMID- 16568797
TI  - Use of stationary and mobile measurements to study power plant emissions.
AB  - This paper presents a technique to study air pollution by combining high spatial
      resolution data obtained by a mobile platform and those measured by conventional
      stationary stations. Conventional stations provide time-series point data but
      cannot yield information that is distant from the sites. This can be complemented
      or supplemented by mobile measurements in the vicinity of the conventional sites.
      Together, the combined dataset yields a clearer and more precise picture of the
      dispersion and the transformation of pollutants in the atmosphere in a fixed time
      frame. Several experiments were conducted in the years 2002-2003 to track the
      impact of power plant plumes on ground receptors in the immediate vicinity
      (within a radius of 30 km) of the plants, using a combined mobile and stationary
      dataset. The mobile data allowed the identification of emissions from coal-fired
      and gas-fired power plants. Coal-fired power plants were the major source of
      sulfur dioxide (SO2), whereas nitrogen oxides (NOx) emitted from the gas-fired
      power plant played an important role in the formation of ozone (O3) at ground
      level. The mobile data showed that two particle size distribution regimes were
      detected: one had a dominant accumulation mode at 0.40-0.65 microm and the other
      at 0.65-1 microm. The existence of particles characterized by their mode at 0.65
      1 microm and formed by in-cloud processes suggests that vehicular emissions were
      not the important source. Other local sources, such as power plants (elevated
      emission), were the likely sources, because Hong Kong does not have much
      manufacturing industry.

PMID- 16568798
TI  - Analysis of aerosol particles and coarse particulate matter concentrations in
      Chillan, Chile, 2001-2003.
AB  - Daily particle samples were collected in Chillan, Chile, at six urban locations
      from September 1, 2001, through September 30, 2003. Aerosol samples were
      collected using monitors equipped with a Sierra Andersen 246-b cyclone inlet on
      Teflon filters. Average concentrations of coarse particulate matter (PM10) for
      the 2001-2003 period ranged from 43.4 microg/m3 to 81.8 microg/m3 across the six
      sites. Annual PM10 concentration levels exceeded the European Union concentration
      limits. Mean PM10 levels during the cold season (April through September) were
      more than twice as high as those observed in the warm season (October through
      March). Average contributions to PM10 from organic matter, soil dust, nitrate
      (NO3-), elemental carbon, ammonium (NH4+), and sulfate (SO4(2-)) were 31%, 27%,
      11%, 8%, 7%, and 5%, respectively. The chemical analyses indicated that
      carbonaceous substances were the most abundant components of PM10 in cold months,
      whereas crustal material was the most abundant component of PM10 during warm
      months. Higher concentration levels were observed in the downtown area suggesting
      a clear anthropogenic origin, whereas in the rural sites the source was mainly
      natural, such as resuspended soil dust associated with traffic on unpaved roads
      and agricultural activities.

PMID- 16568799
TI  - Development and application of a methodology for determining background
      groundwater quality at the Savannah River Site.
AB  - A statistical methodology formulated for defining background or baseline levels
      of constituents of concern in groundwater is presented. The methodology was
      developed for the case where prior delineation of unimpacted areas is not
      possible because of site history and a large set of groundwater monitoring
      measurements exists. Consideration was given to spatial and temporal trends,
      outliers, and final segregation of wells into impacted or unimpacted categories
      to develop probability distributions and summary statistics for each constituent
      evaluated. The formulated approaches were applied to groundwater monitoring data
      for the U.S. Department of Energy Savannah River Site facility, and results for
      four representative constituents (aluminum, arsenic, mercury, and tritium) are
      discussed.

PMID- 16568800
TI  - A combined approach for the evaluation of a volatile organic compound emissions
      inventory.
AB  - Emissions inventories significantly affect photochemical air quality model
      performance and the development of effective control strategies. However, there
      have been very few studies to evaluate their accuracy. Here, to evaluate a
      volatile organic compound (VOC) emissions inventory, we implemented a combined
      approach: comparing the ratios of carbon bond (CB)-IV VOC groups to nitrogen
      oxides (NOx) or carbon monoxide (CO) using an emission preprocessing model,
      comparing the ratios of VOC source contributions from a source apportionment
      technique to NOx or CO, and comparing ratios of CB-IV VOC groups to NOx or CO and
      the absolute concentrations of CB-IV VOC groups using an air quality model, with
      the corresponding ratios and concentrations observed at three sites (Maryland,
      Washington, DC, and New Jersey). The comparisons of the ethene/NOx ratio, the
      xylene group (XYL)/NOx ratio, and ethene and XYL concentrations between estimates
      and measurements showed some differences, depending on the comparison approach,
      at the Maryland and Washington, DC sites. On the other hand, consistent results
      at the New Jersey site were observed, implying a possible overestimation of
      vehicle exhaust. However, in the case of the toluene group (TOL), which is
      emitted mainly from surface coating and printing sources in the solvent
      utilization category, the ratios of TOL/ NOx or CO, as well as the absolute
      concentrations revealed an overestimate of these solvent sources by a factor of
      1.5 to 3 at all three sites. In addition, the overestimate of these solvent
      sources agreed with the comparisons of surface coating and printing source
      contributions relative to NOx from a source apportionment technique to the
      corresponding value of estimates at the Maryland site. Other studies have also
      suggested an overestimate of solvent sources, implying a possibility of
      inaccurate emission factors in estimating VOC emissions from surface coating and
      printing sources. We tested the impact of these overestimates with a chemical
      transport model and found little change in ozone but substantial changes in
      calculated secondary organic aerosol concentrations.

PMID- 16568801
TI  - Application of gaseous ozone for inactivation of Bacillus subtilis spores.
AB  - The effectiveness of gaseous ozone (O3) as a disinfectant was tested on Bacillus
      subtilis spores, which share the same physiological characteristics as Bacillus
      anthracis spores that cause the anthrax disease. Spores dried on surfaces of
      different carrier material were exposed to O3 gas in the range of 500-5000 ppm
      and at relative humidity (RH) of 70-95%. Gaseous O3 was found to be very
      effective against the B. subtilis spores, and at O3 concentrations as low as 3
      mg/L (1500 ppm), approximately 3-log inactivation was obtained within 4 hr of
      exposure. The inactivation curves consisted of a short lag phase followed by an
      exponential decrease in the number of surviving spores. Prehydration of the
      bacterial spores has eliminated the initial lag phase. The inactivation rate
      increased with increasing O3 concentration but not >3 mg/L. The inactivation rate
      also increased with increase in RH. Different survival curves were obtained for
      various surfaces used to carry spores. Inactivation rates of spores on glass, a
      vinyl floor tile, and office paper were nearly the same. Whereas cut pile carpet
      and hardwood flooring surfaces resulted in much lower inactivation rates, another
      type of carpet (loop pile) showed significant enhancement in the inactivation of
      the spores.

PMID- 16568802
TI  - The influences of ambient particle composition and size on particle infiltration
      in Los Angeles, CA, residences.
AB  - Particle infiltration is a key determinant of the indoor concentrations of
      ambient particles. Few studies have examined the influence of particle
      composition on infiltration, particularly in areas with high concentrations of
      volatile particles, such as ammonium nitrate (NH4NO3). A comprehensive indoor
      monitoring study was conducted in 17 Los Angeles-area homes. As part of this
      study, indoor/outdoor concentration ratios during overnight (nonindoor source)
      periods were used to estimate the fraction of ambient particles remaining
      airborne indoors, or the particle infiltration factor (FINF), for fine particles
      (PM2.5), its nonvolatile (i.e., black carbon [BC]) and volatile (i.e., nitrate
      [NO3-]) components, and particle sizes ranging between 0.02 and 10 microm. FINF
      was highest for BC (median = 0.84) and lowest for NO3- (median = 0.18). The low
      FINF for NO3- was likely because of volatilization of NO3- particles once
      indoors, in addition to depositional losses upon building entry. The FINF for
      PM2.5 (median = 0.48) fell between those for BC and NO3-, reflecting the
      contributions of both particle components to PM25. FINF varied with particle
      size, air-exchange rate, and outdoor NO3- concentrations. The FINF for particles
      between 0.7 and 2 microm in size was considerably lower during periods of high as
      compared with low outdoor NO3- concentrations, suggesting that outdoor NO3-
      particles were of this size. This study demonstrates that infiltration of PM2.5
      varies by particle component and is lowest for volatile species, such as NH4NO3.
      Our results suggest that volatile particle components may influence the ability
      for outdoor PM concentrations to represent indoor and, thus, personal exposures
      to particles of ambient origin, because volatilization of these particles causes
      the composition of PM2.5 to differ indoors and outdoors. Consequently, particle
      composition likely influences observed epidemiologic relationships based on
      outdoor PM concentrations, especially in areas with high concentrations of NH4NO3
      and other volatile particles.

PMID- 16568803
TI  - Interaction effects of metals and salinity on biodegradation of a complex
      hydrocarbon waste.
AB  - The presence of high levels of salts because of produced brine water disposal at
      flare pits and the presence of metals at sufficient concentrations to impact
      microbial activity are of concern to bioremediation of flare pit waste in the
      upstream oil and gas industry. Two slurry-phase biotreatment experiments based on
      three-level factorial statistical experimental design were conducted with a flare
      pit waste. The experiments separately studied the primary effect of cadmium
      [Cd(II)] and interaction effect between Cd(II) and salinity and the primary
      effect of zinc [Zn(II)] and interaction effect between Zn(II) and salinity on
      hydrocarbon biodegradation. The results showed 42-52.5% hydrocarbon removal in
      slurries spiked with Cd and 47-62.5% in the slurries spiked with Zn. The analysis
      of variance showed that the primary effects of Cd and Cd-salinity interaction
      were statistically significant on hydrocarbon degradation. The primary effects of
      Zn and the Zn-salinity interaction were statistically insignificant, whereas the
      quadratic effect of Zn was highly significant on hydrocarbon degradation. The
      study on effects of metallic chloro-complexes showed that the total aqueous
      concentration of Cd or Zn does not give a reliable indication of overall toxicity
      to the microbial activity in the presence of high salinity levels.

PMID- 16568804
TI  - Analysis of primary fine particle national ambient air quality standard metrics.
AB  - In accordance with the Clean Air Act, the U.S. Environmental Protection Agency
      (EPA) is currently reviewing its National Ambient Air Quality Standards for
      particulate matter, which are required to provide an adequate margin of safety to
      populations, including susceptible subgroups. Based on the latest scientific,
      health, and technical information about particle pollution, EPA staff recommends
      establishing more protective health-based fine particle standards. Since the last
      standards review, epidemiologic studies have continued to find associations
      between short-term and long-term exposure to particulate matter and
      cardiopulmonary morbidity and mortality at current pollution levels. This study
      analyzed the spatial and temporal variability of fine particulate (PM2.5)
      monitoring data for the Northeast and the continental United States to assess the
      protectiveness of various levels, forms, and combinations of 24-hr and annual
      health-based standards currently recommended by EPA staff and the Clean Air
      Scientific Advisory Committee. Recommended standards have the potential for
      modest or substantial increases in protection in the Northeast, ranging from an
      additional 13-83% of the population of the region who are living in areas not
      likely to meet new standards and thereby benefiting from compliance with more
      protective air pollution controls. Within recommended standard ranges, an optimal
      24-hr (98th percentile)/annual standard suite occurs at 30/12 microg/m3,
      providing short- and long-term health protection for a substantial percentage of
      both Northeast (84%) and U.S. (78%) populations. In addition, the Northeast
      region will not benefit as widely as the nation as a whole if less stringent
      standards are selected. Should the 24-hr (98th percentile) standard be set at 35
      microg/m3, Northeast and U.S. populations will receive 16-48% and 7-17% less
      protection than a 30 microg/m3 standard, respectively, depending on the level of
      the annual standard. A 30/12 microg/m3 standard suite also provides nearly
      equivalent 24-hr and annual control of PM2.5 distributions across the United
      States, thereby ensuring a more uniform and consistent level of protection than
      unmatched or "controlling" and "backstop" standards. This could occur even within
      EPA staff's recommended range of standard suites, where 22-43% of the monitors in
      the country could meet a controlling standard but fail to meet the combined
      backstop standard, resulting in inconsistent short- and long-term protection
      across the country. An equivalent standards combination of 30/12 microg/m3 would
      minimize the wide variation of protectiveness of 24-hr and annual PM2.5
      concentrations. Furthermore, given recent associations of subdaily exposures and
      acute adverse health effects, in the absence of a subdaily averaging metric, a
      stringent 24-hr standard will more effectively control maximum hourly and
      multihourly peak concentrations than a weaker standard.

PMID- 16568805
TI  - Removal of carbonyl sulfide using activated carbon adsorption.
AB  - Wastewater treatment plant odors are caused by compounds such as hydrogen sulfide
      (H2S), methyl mercaptans, and carbonyl sulfide (COS). One of the most efficient
      odor control processes is activated carbon adsorption; however, very few studies
      have been conducted on COS adsorption. COS is not only an odor causing compound
      but is also listed in the Clean Air Act as a hazardous air pollutant. Objectives
      of this study were to determine the following: (1) the adsorption capacity of 3
      different carbons for COS removal; (2) the impact of relative humidity (RH) on
      COS adsorption; (3) the extent of competitive adsorption of COS in the presence
      of H2S; and (4) whether ammonia injection would increase COS adsorption capacity.
      Vapor phase react (VPR; reactivated), BPL (bituminous coal-based), and Centaur
      (physically modified to enhance H2S adsorption) carbons manufactured by Calgon
      Carbon Corp. were tested in three laboratory-scale columns, 6 in. in depth and 1
      in. in diameter. Inlet COS concentrations varied from 35 to 49 ppmv (86-120
      mg/m3). RHs of 17%, 30%, 50%, and 90% were tested. For competitive adsorption
      studies, H2S was tested at 60 ppmv, with COS at 30 ppmv. COS, RH, H2S, and
      ammonia concentrations were measured using an International Sensor Technology
      Model IQ-350 solid state sensor, Cole-Parmer humidity stick, Interscan Corp. 1000
      series portable analyzer, and Drager Accuro ammonia sensor, respectively. It was
      found that the adsorption capacity of Centaur carbon for COS was higher than the
      other two carbons, regardless of RH. As humidity increased, the percentage of
      decrease in adsorption capacity of Centaur carbon, however, was greater than the
      other two carbons. The carbon adsorption capacity for COS decreased in proportion
      to the percentage of H2S in the gas stream. More adsorption sites appear to be
      available to H2S, a smaller molecule. Ammonia, which has been found to increase
      H2S adsorption capacity, did not increase the capacity for COS.

PMID- 16568806
TI  - Why bother with practice guidelines?

PMID- 16568807
TI  - Hypotension and TIA.

PMID- 16568808
TI  - Variables explaining functional recovery following motor stroke.
AB  - Few well-designed descriptive studies focus exclusively on patients after motor
      stroke. This study describes a cohort of participants after motor stroke and
      assesses the extent to which five key variables explain the variation in
      functional recovery 3 months after stroke. Prospective data were collected
      (N=100) on age, lesion volume, motor strength, cognition, and poststroke function
      during the acute care hospital admission. Instruments included magnetic resonance
      imaging (MRI) to provide a measure of lesion volume, the Mini-Mental State
      Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (NCSE) to
      measure cognitive status, and the National Institutes of Health Stroke Scale
      (NIHSS) to measure motor strength. The Functional Independence Measure (FIM) was
      used to measure baseline function and functional recovery 3 months after stroke.
      Descriptive and hierarchical multiple regression analyses were used to describe
      the cohort and predict functional recovery. The means for key variables during
      acute care were 65 (+/-15) years of age, lesion volume 21.5 (+/-44.7) cm3, NIHSS
      6.34 (+/-3.55), MMSE 24.38 (+/-4.82), NCSE 64.33 (+/-13), and FIMTM 94.05 (+/
      19.31). Age, cognitive status, and initial function accounted for 42% of the
      variance in functional recovery 3 months after stroke. Results indicate that
      neuroscience nurses need to add cognition to their focus during the fast-paced
      acute phase of care following motor stroke.

PMID- 16568809
TI  - Posterior lumbar interbody fusion: an old concept with new techniques.
AB  - The estimated cumulative cost of health care attributable to back pain exceeds 25
      billion dollars per year in the United States, and more than 200,000 spine fusion
      procedures are performed each year in an effort to relieve discogenic back pain
      and instability. These numbers are projected to rise in the face of our aging
      population. As new interbody grafting sources have been developed, posterior
      lumbar interbody fusion (PLIF) is being used with increasing frequency. PLIF was
      once a procedure that required extensive dissection of the musculoligamentous
      complex of the dorsal spine. Advances in surgical technique and technology now
      allow access to spinal structures with minimal trauma to surrounding tissue.
      Knowledge of the various fusion procedures can assist nurses caring for the
      unique needs of patients undergoing spinal surgery.

PMID- 16568810
TI  - Nursing staff perspectives on oral care for neuroscience patients.
AB  - Neuroscience patients frequently experience poor oral health and related
      complications because of motor and cognitive dysfunction and the side effects of
      treatments. Inadequate oral care increases plaque deposits, which can lead to
      inflammation, pain, and infection. These patients often depend on nurses for oral
      hygiene. In practice, nurses frequently delegate the delivery of oral care to
      unlicensed personnel, including nursing assistants, technicians, and student
      nurses. Few studies have addressed oral care interventions for neuroscience
      patients. This article identifies oral care interventions practiced by nurses and
      unlicensed personnel caring for neuroscience patients with self-care deficits. An
      investigator-designed survey instrument was used to obtain data from nurses and
      unlicensed personnel working with neuroscience patients in a large hospital.
      Participants responded to questions about products and agents used in care,
      frequency of care, documentation of care, patient risk factors, and system
      support issues such as availability of supplies. Data were analyzed using
      frequency distributions. Findings demonstrated that selection of products and
      agents used for oral care is not always evidence based, that provider preference
      leads to variations in type and frequency of care, and that system issues affect
      care. These findings suggest the need for increased attention to oral care for
      neuroscience patients. Research is needed to further examine the relationship
      between oral care interventions and patient outcomes.

PMID- 16568811
TI  - Self-care needs of caregivers dealing with stroke.
AB  - Education is essential for successful transition from hospital to home, for both
      persons with stroke and their caregivers. Guided by Orem's self-care deficit
      nursing theory, this article identifies self-care needs about which physical and
      occupational therapists believe caregivers most frequently want information. The
      therapists (N=113), who responded to a mailed survey, were mostly White women
      prepared at the graduate educational level in the eastern United States.
      Descriptive statistics revealed that demonstrating safe transfer techniques was
      the most frequently chosen information need (82%) identified by physical and
      occupational therapists surveyed.

PMID- 16568812
TI  - Relapsing MS patients' experiences with glatiramer acetate treatment: a
      phenomenological study.
AB  - This study examined the experiences of a group of patients with relapsing
      multiple sclerosis who received glatiramer acetate for the treatment of their
      illness. Heideggerian phenomenologic research methods drove the data analysis
      process with the Atlas Qualitative Data Analysis software program. The sample was
      a diverse group of 20 men and women 39-64 years of age who had been diagnosed
      with MS 1-21 years and taking glatiramer acetate 1-7 years. Several participants
      had been on other treatments; they related their reasons for choosing this
      treatment and how they manage to persist with taking the daily injections. The
      themes included choosing glatiramer acetate, self-managing care, injecting,
      healthy lifestyle, side effects, support, and participant advice to others.
      Patients with relapsing MS experience a complex process of adjustment when they
      are diagnosed with the disease and come to the decision to start aggressively
      treating the illness. They view glatiramer acetate as an integral part of the
      formula to maintain control over their bodies and manage the disease. Taking the
      glatiramer acetate injection every day becomes easier as time goes on. They
      reported that side effects were minimal and manageable.

PMID- 16568814
TI  - The symptom experience of patients with Parkinson's disease.
AB  - Studying the symptom experience of persons with Parkinson's disease (PD) could
      aid in determining the extent to which particular symptoms and symptom dimensions
      pose a problem and could assist in determining which of these to target for
      interventions. A descriptive correlational design with face-to-face interviews
      was used to study the extent of distress related to 13 symptoms of PD and
      relationships among symptom intensity, frequency, duration, and distress in 85
      persons with PD. The mean number of symptoms reported was 7. The most distressing
      symptom was off time, followed by freezing gait, postural instability, sleep
      disturbance, and difficulty concentrating. Mean symptom distress scores ranged
      from slightly less to more than moderately. Symptom intensity and distress were
      strongly correlated, whereas the relationships of symptom frequency and duration
      to distress varied by symptom. Symptoms found in this study to be most
      distressing should be considered when interventions are being developed. It is
      likely that distress does make symptoms worse, so it is important to assess
      symptom intensity, duration, and frequency as well as distress when interventions
      to reduce distress are evaluated.

PMID- 16568813
TI  - Emotions in relation to healthcare encounters affecting self-esteem.
AB  - This study identifies emotions in patients with epilepsy as a result of
      confirming and disconfirming healthcare experiences. A discussion of emotions as
      a motive for patients' goal-directed actions was a further aim of this study. The
      critical incident method was used for data collection. Emotions occurring in
      confirming and disconfirming healthcare encounters were analyzed using the Belief
      Desire Theory of Emotions and were categorized as basic, complex, or self
      evaluating. Confirming encounters aroused emotions like hope, a feeling of
      security, joy, relief, and pride, while disconfirming encounters aroused emotions
      like despair, fear, unrest, resignation, shame, and guilt. The emotions
      identified in the healthcare encounters were recognized as motives for action. An
      emotion such as a feeling of security aroused a desire in the patients to
      strengthen their positive self and motivated them to have a constructive and
      sympathetic attitude toward the healthcare experience. An emotion such as anger
      caused patients to strive to maintain their self-respect either by avoiding
      difficult situations and ignoring the problem (patients with a low self-esteem)
      or by trying to re-create a positive self-image (patients with a high self
      esteem). Healthcare encounters between patient and caregiver considerably affect
      the patient's emotional status and thereby his or her well-being. The importance
      of establishing healthcare encounters that evoke positive emotions that
      strengthen patients' resources must be addressed in future nursing care.

PMID- 16568815
TI  - Online database and bioinformatics toolbox to support data mining in cancer
      cytogenetics.

PMID- 16568816
TI  - Purification of hearts from zebrafish embryos.

PMID- 16568817
TI  - Automated baculovirus titration assay based on viable cell growth monitoring
      using a colorimetric indicator.

PMID- 16568818
TI  - Horseradish peroxidase-driven fluorescent labeling of nanotubes with quantum
      dots.
AB  - We describe the first enzyme-driven technique for fluorescent labeling of single
      walled carbon nanotubes (SWNTs). The labeling was performed via enzymatic
      biotinylation of nanotubes in the tyramide-horseradish peroxidase (HRP) reaction.
      Both direct and indirect fuorescent labeling of SWNTs was achieved using either
      biotinyl tyramide or fluorescently tagged tyramides. Biotinylated SWNTs later
      reacted with streptavidin-conjugated fluorophores. Linking semiconductor
      nanocrystals, quantum dots (Q-dots), to the surface of nanotubes resulted in
      their fluorescent visualization, whereas conventional fluorophores bound to SWNTs
      directly or through biotin-streptavidin linkage, were completely quenched.
      Enzymatic biotinylation permits fluorescent visualization of carbon nanotubes,
      which could be useful for a number of biomedical applications. In addition, other
      organic molecules such as proteins, antibodies, or DNA can be conjugated to
      biotinylated SWNTs using this approach.

PMID- 16568820
TI  - Combining sequence-specific probes and DNA binding dyes in real-time PCR for
      specific nucleic acid quantification and melting curve analysis.
AB  - Currently, in real-time PCR, one often has to choose between using a sequence
      specific probe and a nonspecific double-stranded DNA (dsDNA) binding dye for the
      detection of amplified DNA products. The sequence-specific probe has the
      advantage that it only detects the targeted product, while the nonspecific dye
      has the advantage that melting curve analysis can be performed after completed
      amplification, which reveals what kind of products have been formed. Here we
      present a new strategy based on combining a sequence-specific probe and a
      nonspecific dye, BOXTO, in the same reaction, to take the advantage of both
      chemistries. We show that BOXTO can be used together with both TaqMan probes and
      locked nucleic acid (LNA) probes without interfering with the PCR. The probe
      signal reflect formation of target product, while melting curve analysis of the
      BOXTO signal reveals primer-dimer formation and the presence of any other
      anomalous products.

PMID- 16568819
TI  - Quantitative assessment of arginine methylation in free versus protein
      incorporated amino acids in vitro and in vivo using protein hydrolysis and high
      performance liquid chromatography.
AB  - Arginine methylation constitutes a posttranslational modification dependent on
      the action of protein arginine methyltransferases (PRMTs). Using S
      adenosylmethionine as a methyl donor, PRMTs catalyze the formation of
      monomethylarginine (L-NMMA), asymmetric dimethylarginine (ADMA), or symmetric
      dimethylarginine (SDMA). Protein arginine methylation is involved in the
      regulation of signal transduction, RNA export, and cell proliferation, but a
      quantitative view of arginine methylation of the cell and tissue proteome remains
      to be performed. In this study, we developed a high-performance liquid
      chromatography (HPLC)-based method to accurately quantify methylated arginines in
      free and protein-incorporated amino acid pools of cell and tissue extracts, using
      protein precipitation and hydrolysis, HPLC separation, and fluorescence detection
      for the simultaneous quantification of L-arginine (L-Arg), L-NMMA, ADMA, and
      SDMA. This method permits accurate assessment of the degree of protein arginine
      methylation in complex biological samples. Using this method, we determined
      dynamic changes in protein methylation in vitro in cells subjected to proteasome
      inhibition. We furthermore demonstrate differential methylation patterns in heart
      and kidney lysates in vivo. Thus, the described method will greatly facilitate
      our understanding of the role of arginine methylation in physiology and
      pathophysiology and of the effects of pharmacological interventions on arginine
      methylation in select cell culture models.

PMID- 16568821
TI  - Multiplex real-time single nucleotide polymorphism detection and quantification
      by quencher extension.
AB  - Multiplex quencher extension (multiplex-QEXT) is a novel closed tube single-step
      method for detection and quantification of several single nucleotide
      polymorphisms (SNPs) simultaneously. The principle of multiplex-QEXT is that 5'
      reporter-labeled probes are 3' single-base-extended with TAMRA dideoxy
      nucleotides if the respective SNP alleles are present. TAMRA can serve as either
      an energy acceptor (quencher-based detection) or donor [fluorescence resonance
      energy transfer (FRET)-based detection] for a wide range of different reporter
      fluorochromes. The extension can therefore be recorded by the respective reporter
      fluorescence change. We evaluated multiplex-QEXT, analyzing four different SNP
      loci in the Listeria monocytogenes inlA gene. Probes labeled with the reporters 6
      FAM, TET, VIC, and Alexa Fluor 594 were used. Responses for the fluorochromes 6
      FAM, TET, and VIC were detected by quenching (decreased fluorescence), while the
      response for Alexa Fluor 594 was detected by FRET (increased fluorescence). We
      evaluated the SNP-allele pattern in 252 different L. monocytogenes strains.
      Multiplex-QEXT gave a good resolution, detecting seven major and five minor
      groups of L. monocytogenes. Comparison with serotyping showed that multiplex-QEXT
      gave better resolution. We also evaluated the quantitative aspects of multiplex
      QEXT. Quantitative information was obtained for all the fluorochrome/probe
      combinations in the sample pools. The detection limits for 6-FAM, TET and Alexa
      Fluor 594 were the presence of the 10% target SNP alleles (P < 0.05), while the
      detection limit for VIC was the presence of the 5% target SNP alleles (P < 0.05).
      Currently, overlap in the fluorescence emission spectra is the limiting factor
      for the multiplexing potential of QEXT. With the emergence of new fluorochromes
      with narrow emission spectra, we foresee great potential for increasing the
      multiplex level in the future.

PMID- 16568822
TI  - Deoxynucleotides can replace dideoxynucleotides in minisequencing by arrayed
      primer extension.
AB  - Scientific literature describing arrayed primer extension and other array-based
      minisequencing technologies consistently cite the requirement for four
      fluorescent dideoxynucleotides (with concomitant absence/inactivation of
      deoxynucleotides) to ensure single-base extension and thus sequence-specific
      intensity data that can be interpreted as a base call or genotype. We present
      compelling evidence that fluorescent deoxynucleotides can reliably be used in
      microarray minisequencing experiments, generating fluorescent sequence extension
      intensity profiles that are homologous to the single-base extensions obtained
      with terminator dideoxynucleotides. Due to the almost 10-fold higher costs (and
      limited fluorophore choice) of many commercially available fluorescent
      dideoxynucleotides, compared to fluorescent deoxynucleotides, as well as other
      potentially constraining intellectual property and licensing issues, this
      hitherto dismissed microarray chemistry represents an important reevaluation in
      the field of array-based genotyping and related enzymology.

PMID- 16568823
TI  - Direct monitoring of vesicular release and uptake in brain slices by multiphoton
      excitation of the styryl FM 1-43.
AB  - Fluorescence imaging using FM 1-43 and related styryl dyes has provided
      invaluable insights into presynaptic function of synapses in culture
      preparations, but has been limited in use for studying central synapses in vivo
      or in brain slices, because of excessive fluorescence background due to
      nonspecific membrane binding of dye. We demonstrate here that focal excitation of
      FM dyes using two-photon laser-scanning microscopy (TPLSM) provides high
      resolution of FM 1-43-labeled nerve terminals in brain slices by suppressing out
      of-focus background and that a readily releasable pool of vesicles can be
      selectively and stably labeled by hypertonic shock despite slice diffusion
      barriers. We find direct TPLSM of FM 1-43-labeled nerve terminals to be superior
      to treatment of slices with either the fluorescent quencher sulforhodamine 101 or
      dye scavenger ADVASEP-7 in resolving nerve terminal against background
      fluorescence, enabling continuous monitoring of vesicular uptake, and release of
      styryl dyes from individual nerve terminals in brain slices.

PMID- 16568824
TI  - Toxic protein expression in Escherichia coli using a rhamnose-based tightly
      regulated and tunable promoter system.
AB  - The refinement of tightly regulated prokaryotic expression systems that permit
      functional expression of toxic recombinant proteins is a continually evolving
      process. Unfortunately, the current best promoter options are either tightly
      repressed and produce little protein, or produce substantial protein but lack the
      necessary repression to avoid mutations stimulated by leaky expression in the
      absence of inducer. In this report, we present three novel prokaryotic expression
      constructs that are tightly regulated by L-rhamnose and D-glucose. These
      expression vectors utilize the Escherichia coli rhaT promoter and corresponding
      regulatory genes to provide titratable, high-level protein yield without
      compromising clone integrity. Together, these components may enable the stable
      cloning and functional expression of otherwise toxic proteins.

PMID- 16568825
TI  - Transparent polymeric cell culture chip with integrated temperature control and
      uniform media perfusion.
AB  - Modern microfabrication and microfluidic technologies offer new opportunities in
      the design and fabrication of miniaturized cell culture systems for online
      monitoring of living cells. We used laser micromachining and thermal bonding to
      fabricate an optically transparent, low-cost polymeric chip for long-term online
      cell culture observation under controlled conditions. The chip incorporated a
      microfluidic flow equalization system, assuring uniform perfusion of the cell
      culture media throughout the cell culture chamber. The integrated indium-tin
      oxide heater and miniature temperature probe linked to an electronic feedback
      system created steady and spatially uniform thermal conditions with minimal
      interference to the optical transparency of the chip. The fluidic and thermal
      performance of the chip was verified by finite element modeling and by operation
      tests under fluctuating ambient temperature conditions. HeLa cells were cultured
      for up to 2 weeks within the cell culture chip and monitored using a time-lapse
      video recording microscopy setup. Cell attachment and spreading was observed
      during the first 10-20 h (lag phase). After approximately 20 h, cell growth
      gained exponential character with an estimated doubling time of about 32 h, which
      is identical to the observed doubling time of cells grown in standard cell
      culture flasks in a CO2 incubator.

PMID- 16568826
TI  - Antibody-free method for protein detection on blots using enzyme fragment
      complementation.

PMID- 16568827
TI  - Dr. William D. Powell receives the Dr. Jack E. Wells Memorial Dedication to
      Dentistry Award.

PMID- 16568828
TI  - More than 56,000 children with disabilities in Tennessee.
AB  - Since 1990, Tennessee has been ranked among the states with a series of health
      and social difficulties. In addition, there are more than 56,000 children with
      disabilities in the state. In an effort to personalize these findings, the
      numbers of children with disabilities are presented by city, metropolitan area,
      county, and congressional districts. There are numerous difficulties associated
      with the delivery of dental care to these children with special needs. If all
      dentists were willing to help, however, each practitioner would need to care for
      twenty of these youngsters.

PMID- 16568829
TI  - [Morphofunctional disturbances in kidneys of sturgeons and bony fishes of the
      Volga-Caspian reservoir under natural conditions].
AB  - By light microscopy, the morphofunctional state of mesonephros was studied for
      various sturgeons and bony fishes taken from natural waters. Different changes
      were recorded in structural-functional elements of nephrons of the mesonephros.
      The most frequent disturbances are hemorrhages in the intertubule tissue of
      kidneys, hyalinosis of vessel walls, swollen epithelium, inflammations. The
      revealed disturbances may be regarded as a response to negative environmental
      impacts.

PMID- 16568830
TI  - [C-terminal sites of caldesmon drive ATP hydrolysis cycle by shifting actomyosin
      itermediates from strong to weak binding of myosin and actin].
AB  - Polarized fluorimetry technique and ghost muscle fibers containing tropomyosin
      were used to study effects of caldesmon (CaD) and recombinant peptides CaDH1
      (residues 506-793), CaDH2 (residues 683-767), CaDH12 (residues 506-708) and 658C
      (residues 658-793) on the orientation and mobility of fluorescent label 1.5
      IAEDANS specifically bound to Cys-707 of myosin subfragment-1 (S1) in the absence
      of nucleotide, and in the presence of MgADP, MgAMP-PNP, MgATPgammaS or MgATP. It
      was shown that at modelling different intermediates of actomyosin ATPase, the
      orientation and mobility of dye dipoles changed discretely, suggesting a multi
      step changing of the myosin head structural state in ATP hydrolysis cycle. The
      maximum difference in orientation and mobility of the oscillator (4 degrees and
      30%, respectively) was observed between actomyosin in the presence of MgATP, and
      actomyosin in the presence of MgADP. Caldesmon actin-binding sites C and B'
      inhibit formation of actomyosin strong binding states, while site B activates it.
      It is suggested that actin-myosin interaction in ATP hydrolysis cycle initiates
      nucleotide-dependent rotation of myosin motor domain, or that of its site for dye
      binding as well as the change in myosin head mobility. Caldesmon drives ATP
      hydrolysis cycle by shifting the equilibrium between strong and weak forms of
      actin-myosin binding.

PMID- 16568831
TI  - [Comparison of geno- and cytotoxicity of methylnitrosourea on MMR-proficient and
      MMR-deficient human tumor cell lines].
AB  - Deficient mismatch repair (MMR) is identified as a mutation of one of four major
      MMR genes and(or) microsatellite instability. These genomic changes are used as
      markers of MMR status of the heredity nonpolyposis colorectal cancer (HNPCC)
      spectrum tumors--familial and sporadic tumors of colon and extracolonic cancers
      fulfilling Amsterdam clinical criteria II. MMR-deficiency results in mutator
      phenotype and resistance to geno- and cytotoxicity of alkylating agents. The main
      cytotoxic damage to DNA in response to chemical methylation is O6-methylguanine
      (O6-mG). The secondary DNA strand breaks, which are formed during the MMR
      functioning, are proposed to be required for methylation induced cytotoxicity. We
      have assumed that the secondary double stand breaks (DSB) upon DNA methylation
      are able to represent functional efficiency of MMR in cells. The purpose of the
      paper was to test this assumption on human tumor cells differing in MMR-status
      and pulse-treated with methylnitrosourea (MNU). We used 3 cell lines: HeLa (MMR
      competent endometrial tumor cells), HCT116 (MMR-deficient colorectal carcinoma
      cells), and Colo320 (sigmoid intestine tumor cells with uncharacterized MMR
      status). DSBs were evaluated with neutral comet assay. Cytotoxicity/viability was
      evaluated with MTT-asay and apoptotic index (frequency of morphologically
      determined apoptotic cells). We show that 1) cytotoxic effect of MNU (250 microM)
      on HeLa cells was exhibited 3 days after pulse-treatment of cells with MNU; 2)
      DSBs occurred 48 h after the drug treatment but prior to the onset of apoptosis
      of HeLa cells; 3) MMR-deficient HCT116 cells were resistant to the drug: no
      decreased viability, DSBs and apoptosis were observed during 3 days after cell
      treatment. Both cell lines exhibited high sensitivity to etoposide, classical
      inductor of unrepairable DSBs and p53. Etoposide has been found to induce DSBs in
      6-12 h, which was followed by apoptosis (in 24 h). Colo320 cells exhibited
      intermediate position between HeLa and HCT116 cell lines in regard to sensitivity
      to MNU according to MTT-assay and the number of secondary DSBs formed in MNU
      treated cells. Nevertheless, in contrast to HeLa cells, these breaks did not
      induce apoptosis in Colo320 cells. Our data confirm the assumption about
      case/effect relationship between secondary DNA double strand breaks, induced by
      monofunctional methylating agent MNU, and functioning of MMR in human tumor
      cells.

PMID- 16568832
TI  - [Low-molecular peptides from tissues of hibernating and cold-adapted animals
      influence cell proliferation in the Ehrlich ascitic carcinoma].
AB  - Polypeptides with cytostatic activity are known to be present in animal tissues
      during winter dormancy. A 1-10 kDa polypeptide fraction with cytostatic activity
      was obtained from brain tissue of hibernating ground squirrels and cold-adapted
      Yakut horses. The pattern of cytostatic activity of this fraction towards tumor
      cells is of great interest. We present results testifying to cytostatic activity
      of this fraction towards the Ehrlich ascitic carcinoma cells. The cytostatic
      effect is realized in tumor cells at the genetic level.

PMID- 16568833
TI  - [The intracellular calcium and mechanisms of endocytosis of synaptic vesicles at
      the frog nerve ending].
AB  - In the experiments on frog motor nerve endings of cutaneous pectoris muscle, made
      by extracellular recording of synaptic signals, it has been shown that the
      increase in intracellular calcium ion concentration in the nerve ending (by
      enhance of extracellular potassium ion concentration, or by addition of caffeine)
      leads to an increase in the miniature end-plate potential frequency, which is
      preserved over the whole period (about 10 min) of action of these substrates. The
      rhythmic stimulation of motor nerve (20 or 100 imp/s) quickly leads to a decrease
      in the end plate potentials amplitude. It has been shown by fluorescent
      microscopy with the use of endocytotic marker FM 1-43 that in the course of a
      short time exposition (5 min) in a high potassium solution (40 mM) or caffeine (5
      mM), light spots appeared in the nerve ending. This shows that synaptic vesicles
      undergo intensive processes of endocytosis. During a longer exposition (30 min)
      no light spots were revealed, whereas the nerve ending width increased. This data
      allowed to propose that the process of endocytosis was blocked. In the presence
      of even lower concentrations of potassium ions and caffeine, and during a long
      rhythmic stimulation (20 or 100 imp/s) no blocking of endocytosis was revealed.
      It is concluded that high concentrations of intracellular calcium in the frog
      motor nerve ending leads to a reversible block of endocytosis, while exocytosis
      in synaptic vesicles is proceeding.

PMID- 16568834
TI  - [Activation of transcriptional factors stat5 and stat3 during human T-lymphocyte
      proliferation induced by different mitogenic stimuli].
AB  - The activation of closely related transcription factors STAT5alpha and STAT5beta
      is one of the key signalling events during interleukin-2-dependent stage of T
      lymphocyte proliferation. Here, we investigate the activation of STAT5 and STAT3
      family proteins on different stages of T-cell proliferative response to various
      mitogenic stimuli. The activation of STAT proteins was estimated according to
      their tyrosine phosphorylation. Isolated peripheral blood lymphocytes were
      stimulated by phytogemagglutinin (PHA), or by phorbol-12,13-dibutyrate (PDBu)
      with calcium ionophore--ionomycin, or by exogenous interleukin-2 (IL-2). After
      activation of T-cells by PHA as well as by PDBu with ionomycin we observed
      phosphorylation of STAT5 not earlier than in 5 h. The maximum phosphorylation (by
      10 times and more, as compared to control resting lymphocytes) was detected
      following 24 h of mitogen stimulation. In the lymphocytes pretreated by PHA in
      submitogenic concentration, exogenous IL-2 induces a proliferative response. High
      phosphorylation level of STAT5 was determined 10 min after addition of IL-2 and
      kept for the next 24 h. In contrast to STAT5, some basal phosphorylation of STAT3
      was found in resting and PHA-pretreated T-cells. The profile of phosphorylation
      STAT3 during mitogen-induced activation is more leveled. An immunosuppressant
      cyclosporine A taken at antiproliferative concentration decreased phosphorylation
      of both STAT5 and STAT3 by 1.5-2.0 times at early stages, as well as at late
      stages of activation. A correlation between alteration in tyrosine
      phosphorylation level of STAT5 and the expression of the high affinity IL-5
      receptor was established. Taken together, we report that the increased STAT5
      phosphorylation can serve as a marker of T-lymphocyte entrance into IL-2
      dependent stage of proliferation after T-cell activation by different mitogens.

PMID- 16568835
TI  - [The ultrastructural patterns of germinal and yolk granules in oocytes and
      embryonic cells of the holothurian Apostichopus japonicus].
AB  - The yolk germinal granules in oocytes and embryonic cells of Apostichopus
      japonicus were studied by transmission electron microscopy. Analysis of the
      features of synthesis and utilization of yolk granules made it possible to reveal
      ultrastructural criteria to distinguish between granules of the forming and
      utilized yolk, and germinal granules. Based on these findings, the authors
      suppose that identification of germ plasm elements in oocytes and embryonic cells
      of A. japonicus is quite possible with ultrastructural analysis only, and does
      not require utilizing molecular markers.

PMID- 16568836
TI  - [Structural-functional organization of Golgi apparatus].
AB  - This review is dedicated to the structure and function of Golgi apparatus (GA).
      It summarizes contemporary data published in numerous experimental papers and in
      several reviews. Possible ways of intra-Golgi transport of proteins, existent
      models of structural and functional organization of Golgi organelle, as well as
      the issues of its biogenesis, posttranslational modification and sorting of
      proteins and lipids, and mechanisms of their trafficking are discussed. Special
      attention is paid to the role of coatomer proteins (COPI, COPII and clathrin),
      fusion proteins (SNAREs), and small GTPases (ARF, SARI) in the secretory pathway.
      In addition, the phenomena of ultrastructural alterations of GA due to various
      functional conditions and physiological stimuli are specifically accented. We
      included in this review our original data on a probable involvement of GA in
      water transport, and on the organization of atypical GA in microsporidia-
      intracellular parasitic protists.

PMID- 16568837
TI  - [Moscow "RODON" Industrial Research Association (to the 45th anniversary of
      foundation)].

PMID- 16568839
TI  - [Results of radiation monitoring in Moscow region over 1957-2005].
AB  - The article contains data on radiation situation in Moscow region,
      characteristics of overall beta-activity of ambient air, fall-out density,
      radionuclide contents of foods. Radionuclides content of environment appeared to
      decrease by 2-3 orders. Individual doses of internal irradiation for Moscow
      population are 100 times lower than the levels legally set for technogenic
      sources.

PMID- 16568838
TI  - [System preserving radiation safety for Moscow population].
AB  - Radiation safety system functioning on Moscow territory enables to control
      potential dangerous sources, opportunely reveal and liquidate accidents and
      pollutions, forecast degree of radiation jeopardy according to its components.

PMID- 16568840
TI  - [Removing radioactive waste from enterprises and territories of Moscow and
      central region of Russia is a main goal of RADON Industrial Research
      Association].
AB  - The article contains brief historical data on foundation of radiation accident
      department in "RADON" Industrial Research Association, list and extent of the
      department works since 1995 on liquidation of various radioactive pollutions,
      decontamination methods applied, operative equipment and devices. The authors
      present methodic documents elaborated by the department specialists on
      decontamination of territories, compartments, etc.

PMID- 16568841
TI  - [Experince accumulated by RADON Industrial Research Association in treating
      radioactive waste].
AB  - To reduce volume of radioactive waste for long storage, specialists in "RADON"
      Industrial Research Association according to qualitative contents of the waste
      use methods of filtration and selective sorption of radionuclides, electrolysis,
      monoselective purification, burning, plasmic burning and pressing. Overall volume
      of the waste processed by various plants exceeds 50 thousand cubic meters. The
      mentioned technologies could be widely used in radiochemical works and other
      nuclear energy plants.

PMID- 16568842
TI  - [Processing of liquid radioactive waste by RADON Industrial Research
      Association].
AB  - The authors present experience accumulated by "RADON" Industrial Research
      Association in treating liquid radioactive waste. According to the presentation,
      activities of "R ADON" Industrial Research Association develop in three
      directions--evolving technical means to purify radioactive waters in "RADON"
      Industrial Research Association, advancing mobile plants to purify radioactive
      waters in other institutions, elaborating new technologies for liquid radioactive
      waste purifications within numerous national and international projects and
      agreements with various organizations (including those associated with nuclear
      power stations and nuclear submarines).

PMID- 16568843
TI  - [Modyfying complex additives in technologies for cementing radioactive waste].
AB  - The article presents results obtained in studies concerning properties of cement
      compounds with radioactive waste, if made with modifying complex additive.
      Modifying complex additive was proved to influence positively on technologic
      parameters of cementing liquid and solid radioactive waste, on possible lower
      volume of cemented waste vs. the volumes obtained through traditional cementing
      methods without the modifying complex additive, on regulated qualities of end
      cement compounds with radioactive waste and prevention of biologic corrosion in
      presence of the modifying complex additive.

PMID- 16568844
TI  - [Hight-temperature matrices to immobilize radioactive waste].
AB  - To immobilize liquid radioactive waste with medium activity level, specialists of
      "RADON" Industrial Research Association use borosilicate glass incorporating up
      to 30-35 mass percent of radioactive waste, with sulfate and chloride ions
      content up to 1 mass percent. To increase those concentrations, the authors
      suggest putting phosphate or vanadate additives into borosilicate glass or using
      phosphate glass. In vitrification of solid waste, for instance burning oven slag,
      sodium silicate or dolomite and bentonite mixture are suggested as additives.

PMID- 16568845
TI  - [Lauuching cold crucible using microwave irradiation].
AB  - Experimental studies covered ultra-high frequency waves melting of start charge
      based on sodium nitrate and put on fluid glass surface to provide subsequent
      heating of the fluid glass in melting pot "cold crucible"--device for
      vitrification through high frequency inductive heating.

PMID- 16568846
TI  - [Stabiltiy and barries function provided by sanitary protective zone of
      radioactive waste neutralization site, according to data obtained through
      geoinformative technologies].
AB  - The authors defined a radioactive waste neutralization and disposal site as a
      complex of industrial chambers with used territory of ground with burial places,
      buffer sanitary protection zone and observation zone. This area is a complicated
      geotechnical zone where natural communities develop under chronic exposure to
      natural and artificial radionuclides coming from both global and technogenic
      sources. Using geoinformative technologies of radioecologic safety, the authors
      evaluated protective functions of buffer zone, its biopotential and stability to
      specific type of nature management. The studies helped to identify sorption and
      migration capacity of the territory.

PMID- 16568847
TI  - [More than half a-century at the head of Journal "Vestnik Khirurgii im I.I
      Grekova"].

PMID- 16568848
TI  - [Andrej Vladimirovich Gulyaev (1904-1984)].

PMID- 16568849
TI  - [Surgical treatment without recurrences ventral hernias as a social problem].
AB  - The authors have analyzed social aspects of surgical treatment of postoperative
      ventral hernias and described results of the surgical treatment of 149 patients.
      Specific measures used in preoperative preparation and in operative treatment of
      elderly and senile patients are considered. Long-term results of surgical
      treatment of 76 patients have been studied who had undergone plasty of the
      anterior abdominal wall with the application of a reticulate polypropelene
      explant. This method was shown to be pathogenetic and highly reliable for
      surgical treatment of postoperative ventral hernias.

PMID- 16568850
TI  - [X-ray diagnostic parallels in estimation of the degree of portohepatic
      circulation reduction in patients with liver cirrhosis].
AB  - The data obtained in a retrospective analysis, angiographic and
      hepatoscintigraphic examinations of 86 patients (aged from 12 to 64 years) with
      liver cirrhosis (LC) treated during the period from 1998 through 2003 were
      analyzed. Among them there were 64 men and 22 women. The investigations performed
      have shown that the angiographic data obtained in LC patients determine not only
      the topographic interaction of the major and collateral vessels of the porto
      lienal pool that is of principal significance in the decision for the method of
      surgical correction in portal hypertension but also allow an estimation of the
      picture of the hepatopetal blood flow inversion. The data obtained allowed the
      authors to define three degrees of reduction of the hepatopetal blood flow. A
      conclusion was made that the degree of reduction of the hepatopetal blood flow
      when compared was the findings of angiographic and radionuclide examinations were
      of great prognostic significance for an estimation of the necessary decompression
      and possible maximal preservation of the hepatopetal blood flow with respect to
      the preoperative level.

PMID- 16568851
TI  - [Improvement of visualization--a real way to increase the effectiveness of
      endoscopy in continuing gastroduodenal bleedings].
AB  - A special device--"a low temperature washer"--had been developed and introduced
      into practice for the improvement of a visual picture in an endoscopic
      examination of bleeding gastroduodenal ulcers. An estimation of the results of
      using the device in emergency endoscopic examinations was made in an analysis of
      results of the diagnosing and treatment of 246 patients (1999-2003). This device
      allowed almost 100% elevation of the diagnostic and 2.5 times higher medical
      effectiveness of emergency endoscopy, and 2.5 times less amount of operations
      performed at highest bleeding.

PMID- 16568852
TI  - [Residual fibrous formations after hydatidectomy and their clinical
      significance].
AB  - After radical hydatidectomies in the organ still remains a fibrous cyst capsule
      in which the maternal chitinous membrane has signs of destruction (the second
      phase of vital activity). Germinal elements capable to transform in cyst
      satellites can be introduced into the fibrous cyst capsule. Most cyst-satellites
      while growing break inside the initial cyst. The residual fibrous cyst capsule
      which is in the second phase should be considered as a risk factor of recurrence
      and so hydatidectomy must be followed by intraoperative ultrasound scanning of
      the peri-parasitogenic space for a detection of cyst-satellites as well as by
      anti-recurrence courses of medication at the postoperative period. In the USI the
      area of localization of the residual fibrous capsule is visualized as
      polymorphous focal structures which can be classified as: an unechogenic focus (a
      residual cavity); heterogeneity of the echo-structure with minimal unechogenic
      foci; heterogeneity of the echo-structure with prevailing unechogenic foci (a
      mixed type structure); hyperechogenic focus (focal fibrosis). The optimal
      strategy of management of the postoperative period can be worked out by using USI
      in the field of liquidation of the residual cavity and by getting an exact
      character of its echo-tomoscopic picture.

PMID- 16568853
TI  - [On debatable questions of percutaneous sclerosing therapy of benign tumors of
      the thyroid gland].
AB  - Certain debatable questions of the mechanism of reducing the thyroid nodules,
      technical details of the method are discussed on the basis of considerable
      clinical experiences with percutaneous sclerosing ethanol therapy of benign
      thyroid nodules (783 patients) and results of experiments in 150 animals and 11
      volunteers. A precise preliminary calculation of the amount of ethanol introduced
      in one session of the sclerosing therapy and during the whole course of treatment
      was shown to be necessary and possible. A pronounced inflammatory response during
      the sclerosing therapy was proved to take place but when ethanol got beyond the
      limits of the thyroid gland. So, the ethanol destruction of the thyroid tissue is
      possible in the situation of recurrent disease. The degree of a reduction of the
      thyroid nodules depends not on their initial size but on their inner structure
      and the development of the fibrous tissue.

PMID- 16568854
TI  - [A combination of diseases of the thyroid and asymptomatic adenoma of the
      parathyroid glands].
AB  - The authors have analyzed the cases of diagnosis of asymptomatic tumors of the
      parathyroid gland made during 8814 operations on the thyroid in the period from
      1995 through 2004. The probability of detecting parathyroid incidentalomas in
      different forms of goiter was calculated which reaches 0.4%. A precision
      technique of operating allows the parathyroid tumors to be detected at the
      preclinical stage in all patients apart from a removal of the necessary volume of
      the thyroid tissue, guaranteed preservation of the laryngeal nerves and
      parathyroid glands.

PMID- 16568855
TI  - [Papillary thyroid carcinoma: clinical manifestations, recurrences and
      prognosis].
AB  - Papillary carcinoma was detected in 2512 cases out of 3048 patients with
      differentiated thyroid carcinoma who underwent surgery during a 61-year period at
      the Mayo Clinic. The clinical picture of papillary carcinoma was shown to be
      interrelated with the appearance of recurrences, metastases and with prognosis
      for life. Lethality and survival were estimated within 5, 10, 20, 30 and 40 years
      depending on the stage of the disease that allowed a separation and comparison of
      groups of low and high risk in connection with the further prognosis. Median
      follow-up was 14 +/- 0.9 years and the longest follow-up was 60 years. It was
      shown that if the tumor was confined to the neck and the tumor was grossly
      resected the survival rate did not differ from the level predicted by an
      actuarial curve, and the appearance of metastases in regional lymph nodes
      represented no real threat in low-risk patients.

PMID- 16568856
TI  - [Stenting for treatment of scarry stenoses of the esophagus in children].
AB  - The article contains results of examination and treatment of 160 children with
      scarry stenoses of the esophagus. Radical operations were made in 4 children, 4
      children were treated by a direct bougieurage, 73 by bougieurage with a thread,
      in 79 children esophagus stenting was used. Stents of different shape and
      different methods of their fixation were used. The time of treatment and number
      of bougieurages in children when stents were used was much less than when only
      bougieurage was used although the same results were obtained.

PMID- 16568857
TI  - [Polyenzymatic therapy in prevention of adhesive processes in the abdominal
      cavity in children].
AB  - The clinical investigation included 48 patients with acute adhesive intestinal
      obstruction resulting from appendectomy and an analysis of the cytokine status in
      34 children with acute phlegmonous appendicitis. The patients were divided into
      two groups: a "polyenzyme" group and a "monoenzyme" group (Hyaluronidase). In the
      "polyenzyme" group the children were given the preparation Wobenzym in addition
      to the complex therapy, in the "monoenzyme" group--electrophoresis of
      Hyaluronidase. In the "monoenzyme" group there were 2 cases of intestinal
      obstruction. The patients from the "polyenzyme" group had no postoperative
      complications. Wobenzym was shown to reduce (p < 0.05) the level of pro
      inflammatory cytokines (IL-2, IL-6, TNF-alpha) and to increase the level of anti
      inflammatory cytokine (IL-4). Using the polyenzyme preparations after abdominal
      operations in children was found to promote the reduction of intra-abdominal
      adhesion and inflammatory processes.

PMID- 16568858
TI  - [Operative treatment of severe forms of congenital elevation of the scapula in
      children].
AB  - The article presents results of operative treatment of 36 children with severe
      forms of congenital high scapula. An original and used by us method of operative
      treatment of children with a severe form of Sprengel deformity is described.
      Distinctive features of the method are: mobilization of the suprascapular
      vascular-nervous bundle, correction of scapula deformities followed by a recovery
      of congruency of the sliding surfaces of the scapula and chest, physiological
      fixation of the scapula in the new place, separating off the paravertebral
      muscles and their sewing on to the medial edge of the scapula that allows a
      recovery of the function of lost trapezoid and rhomboid muscles and in some cases
      a shortening osteotomy of the clavicle is performed preventing the descending of
      the scapula. An analysis of the external view of the shoulder made after the
      operation has shown that the result was good in 57.5% of children, satisfactory
      in 42.5%. The functional indices characterizing the increased amplitude of
      movements in the shoulder joint were good in 47.5%, and satisfactory in 52.5%.
      The cosmetic and functional results of the treatment allow the developed
      technique to be recommended for treatment of severe forms of the Sprengel disease
      in children.

PMID- 16568859
TI  - [Elimination of anatomical and esthetic lesions in patients with rough infected
      defects of tissue].
AB  - The reconstructive plastic operations were made in 217 patients with infected
      tissue defects with continuous regional infusions or with a simultaneous
      sanitizing operation, or within 7-15 days. Skin plasty, catheterization of the
      main artery (210), secondary surgical treatment and sequest-necrectomy (185),
      osteosynthesis (106), bone plasty (69) and others (1118 operations in all) were
      carried on in all the patients, i.e. 5.1 operations per each patient with artery
      catheterization taken into account. The method of plastic replacement was chosen
      individually depending on localization, depth and spread of the defect. Good and
      satisfactory results were obtained in all the patients with no esthetic
      impairments.

PMID- 16568860
TI  - [Evolution of the methods of peritonization of the vermiform process stump in
      acute destructive appendicitis complicated by typhlitis].
AB  - A comparative assessment of effectiveness of various non-traditional and non
      typical variants of appendectomy was made with using non-standard (non-classical)
      methods of treatment and peritonization of the vermiform stump developed by
      different authors for destructive forms of acute appendicitis complicated by
      inflammatory infiltration of the blind gut cupola and typhlitis. An analysis of
      results of using the proposed non-typical technical methods and techniques as
      well as an assessment of the authors' technique used in 43 patients suggests that
      the above variants of peritonization of the vermiform process stump should not be
      considered as competing. Each of the methods can be successfully used depending
      on the concrete clinical situations and for the corresponding indications as the
      most optimal method of choice or as an alternative of the classical variant of
      appendectomy in patients with acute destructive appendicitis complicated by
      inflammatory infiltration of the blind gut cupola and typhlitis.

PMID- 16568861
TI  - [Drainage of the pancreatic duct].
AB  - An original drainage was used for preventing acute postoperative pancreatitis
      which had a construction providing preventive decompression of the pancreatic
      duct system acting on the pathogenetic mechanisms of its development, i.e.
      intraduct hypertension. The principal distinction of the proposed drainage
      construction is the duct system decompression with the saved physiological way of
      outflow of the pancreas secretion that eliminates the shortcomings of the
      external drainage. The drainage described was used in 6 patients after operations
      on the major duodenal papilla, cicatricial stricture of the papilla,
      choledocholithiasis. High clinical effectiveness of the method of the pancreatic
      duct system decompression is shown.

PMID- 16568862
TI  - [Surgical strategy for combined esophagogastroduodenal bleedings in liver
      cirrhosis patients with portal hypertension].
AB  - Under analysis were results of treatment of 83 patients with bleedings resulting
      from portal hypertension against the background of liver cirrhosis combined with
      ulcer disease of the stomach and/or duodenum. In 49.4% of the patients the
      sources of bleedings were varicose veins of the esophagus and stomach, in 37.3%-
      ulcers, in 13%--a combination of ulcer and erosion of the varicose veins.
      Emergency operations were made on 33.8% of patients, urgent--on 22.1%, planned
      operations on 45.1%. Recurrences were noted in 15.4% of urgent and emergency
      operations, lethality--10.3%. After planned operations lethality was 0%.

PMID- 16568863
TI  - [Acute gastrointestinal bleedings of tumorous etiology].
AB  - A retrospective analysis of treatment of 436 patients with acute bleedings from
      tumors of the gastrointestinal tract was made. Elderly and senile patients made
      up 72% of the hospitalized patients. The emergency complex diagnostics in 75% of
      the patients under conditions of a multi-profile hospital allowed the source of
      bleeding to be detected during the first day, the strategy of treatment being
      also determined. Radical operations could be fulfilled both in emergency and
      planned order on most patients. Lethality of patients with tumors of the stomach
      and colon after radical operations was 10%, after palliative operations 29.5% and
      27.9% respectively. Acute bleedings from tumors of the gastrointestinal tract is
      not the absolute sign of the patient being inoperable.

PMID- 16568864
TI  - [Lymphoma of the duodenum after a chemical burn complicated by mechanical
      jaundice].

PMID- 16568865
TI  - [Small pelvis abscess as a manifestation of tertiary syphilis].

PMID- 16568866
TI  - [Spontaneous taxis of Littre's hernia].

PMID- 16568867
TI  - [Clinico-economical aspects of anesthesiology].

PMID- 16568868
TI  - [Evgeny Mikhajlovich Margorin (1908-1984)].

PMID- 16568869
TI  - [Combined palliative treatment of lung cancer using endoscopic methods].
AB  - The review is devoted to using endoscopic methods as a stage of a combined
      palliative treatment of inoperable lung cancer and elucidates the theoretical and
      practical aspects of using the main up-to-date methods of acting on the tumor
      process during the endoscopic interventions: electro-, radio, cryosurgical,
      laser, stenting, brachytherapy, conservative methods. Advantages and shortcomings
      of these methods are discussed as well as indications and contraindications to
      their application, possible complications and methods of their elimination and
      prevention.

PMID- 16568870
TI  - [Wounds of the gluteal area].

PMID- 16568871
TI  - Is nursing becoming a political minefield of the unachievable?

PMID- 16568872
TI  - Health choices for an ageing population.

PMID- 16568873
TI  - Shrouds of silence: three women's stories of prenatal loss.
AB  - OBJECTIVE: To give voice to the experiences of women who have suffered a prenatal
      loss prior to a full term pregnancy. DESIGN: A descriptive, exploratory
      qualitative study using mini-biographies was used. In-depth interviews were
      conducted with women to record their experiences and stories. Interviews were
      transcribed and the patterns that emerged from the data were identified and
      themes generated. SUBJECTS: The mini-biographical stories of three women were
      gathered. Interviews occurred in the women's homes. The women were recruited
      through an advertisement in the Stillbirth and Neonatal Death Support (SANDS)
      newsletter. RESULTS: The stories revealed the tragedy, pain and silence endured
      by these women, as they live with loss and grief. Common themes emerged from
      their stories highlighting grief, isolation, anger and self-blame in the face of
      their loss and subsequent full term pregnancy. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: The emergent theme suggests that further research needs to explore how
      society and the health care community may compound women's grief and isolation
      and in-turn perpetuate their feelings of anger. In telling their stories, these
      women give voice to their current health care practices may be modified to better
      support the needs of women who have suffered a prenatal loss and also points to
      the need for further research. Specifically, the study identifies a need for
      nurses and midwives to offer sensitive care, acknowledgment of previous loss and
      supportive counseling strategies for women following prenatal loss and during
      antenatal care for subsequent pregnancies.

PMID- 16568874
TI  - Parents' preferred child health information sources: implications for nursing
      practice.
AB  - AIM: To ascertain parents' preferences in sources of health information
      concerning their children's general health care needs, and caring for their
      children when they are sick. DESIGN: Exploratory/descriptive design. A telephone
      survey secured data for the study and qualitative content analysis and
      descriptive statistics were used for analysis. SETTING & PARTICIPANTS: Part 2 of
      a larger study in which Part I evaluated parents' satisfaction with a paediatric
      telephone triage service. One hundred of the 101 parents who were recruited for
      Part 1 of the study participated in Part 2, an examination of parents'
      preferences in information sources relating to their child's health. MAIN OUTCOME
      MEASURES: Parents' preferences in child health information sources varied
      according to the perceived severity of their child's illness. RESULTS: Parents
      frequently selected more than one item on a list of health information sources
      provided. In a non-urgent situation when children were sick a total of 170
      selections were made by parents, with 'telephone advice line' the source most
      frequently selected (58, 34%), followed by general practitioner (27, 15.8%). In
      an emergency situation the most frequently selected information source was again
      'telephone advice line' (74, n=129, 57.4%), followed by 'other' (31, n=129,
      24.3%) often identified as relating to dialing '000' (Australia's emergency
      services number). Finally, when parents required information about the general
      health care needs of their child, 'other' (most frequently identified as books)
      was selected on 40 (n=185, 21.6%) occasions, followed by child health clinic (35,
      n= 185, 18.9%). CONCLUSION: Parents prefer to receive information about the
      health care needs of their child from another person rather than a printed or
      audio-visual source.

PMID- 16568875
TI  - Warfarin use in the elderly: the nurses' perspective.
AB  - OBJECTIVE: To explore the barriers to warfarin use from the perspective of nurses
      working in aged care. DESIGN: A qualitative study, involving a semi-structured
      group interview, during March-April 2001. SETTING AND SUBJECTS: Eleven nurses,
      employed within the catchment of the Northern Sydney Area Health Service, who
      were involved in the care of elderly warfarinised patients. MAIN OUTCOME MEASURE:
      Identification, via thematic analysis, of the main themes underpinning the
      nursing perspective on warfarin use in this setting, with regard to their
      perceived role/s, experiences with patients, and potential strategies for
      managing the therapy. RESULTS: Five main themes were identified: perceived
      patient attitude toward warfarin; barriers to the use of warfarin; expressed lack
      of confidence in the processes involved; nurses' role in warfarin use; and
      strategies to improve warfarin use. Nurses were concerned about warfarin use in
      the elderly, but felt they had a limited capacity to intervene. CONCLUSION:
      Nurses are potentially underutilised as a resource and support for both patients
      and prescribers, in the management of warfarin therapy.

PMID- 16568876
TI  - Predictors of dietary and health supplement use in older Australians.
AB  - OBJECTIVE: This study aimed to identify the health conditions and symptoms that
      predicted dietary and health supplement use in older Australians. DESIGN: Almost
      2,500 Australians aged 65 years and over were randomly selected from the 2000
      Australian Electoral Commission roll. All states and territories were
      proportionally represented in the sample. Data were obtained using a self
      administered postal survey. SUBJECTS: Approximately 1,200 individuals (51% males
      and 49% females) aged between 65-98 years completed the survey. RESULTS: At the
      time of survey, 43% (n=548) reported using some form of supplement. Supplement
      use was significantly associated with gender (female) and chronic musculoskeletal
      ailments such as arthritis, osteoporosis and generalised back or neck problems. A
      diagnosis of hypertension or a heart condition were significant barriers to
      supplement use in this sample. The most common potential drug-supplement
      interaction was between calcium supplements and antihypertensives. CONCLUSION:
      Older supplement users may be of the opinion that supplements offer relief from
      the pain and suffering associated with their medical problems. If so, current
      supplement patterns would indicate that they are misguided. Nurses have an
      important role to play in encouraging older individuals to disclose their use of
      supplements to all health professionals involved in their continuing care.

PMID- 16568877
TI  - Medication administration errors: understanding the issues.
AB  - OBJECTIVE: This paper surveys current literature related to medication
      administration errors, the role of nurses in such errors, and current initiatives
      that are underway within New Zealand to address this aspect of patient safety.
      SETTING: The literature review focused on research that primarily addresses the
      issues related to medications that arise in tertiary care facilities. PRIMARY
      ARGUMENT: Medication administration errors are reported to occur in one in five
      medication dosages. Such events have long been scrutinised, with the primary
      focus being the practice of nurses and their role in medication error. Analysis
      of such events frequently identifies the nurse as the deliverer of unsafe
      practice. However, over the past few years a shift in how medication errors are
      understood has led to the identification of systems-related issues that
      contribute to medication errors. CONCLUSION: Initiatives such as the 'Quality and
      Safe Use of Medicines' raise the opportunity to address some of the safety
      related issues with a view to enhancing patient safety. A call for nurses to pre
      emptively drive and contribute to these initiatives, along with the development
      of nursing led research, is offered.

PMID- 16568878
TI  - Mismanagement of delerium places patients at risk.
AB  - OBJECTIVE: This paper discusses the problem of delirium and the challenges of
      accurately assessing, preventing and managing patients with delirium in an acute
      care setting. PRIMARY ARGUMENT: Acute confusion, also known as delirium, is
      misdiagnosed and under-treated in up to 94% of older patients in hospitals. With
      the ageing population, this problem will increase dramatically in the Australian
      setting. Managing patients with delirium is challenging not only for the
      management of their basic nursing care needs but also because they are prone to
      adverse events such as falls and medication problems. In order to address this
      issue it is vital that health care professionals routinely assess patients for
      signs of delirium. The current 'gold standard' for assessing delirium is the use
      of the Confusion Assessment Method (CAM) which has been developed based on the
      diagnostic criteria set by the Diagnostic and Statistical Manual of Mental
      Disorders DSM-IV and can be used by non-psychiatrists. Further, increased
      attention should be given to the prevention and management of delirium and the
      use of orientation and validation therapy. CONCLUSION: Research indicates that
      early identification and intervention can help to limit any negative effects or
      adverse events. Increasing knowledge and awareness of early detection and
      efficient management of delirium is the first step toward prevention.

PMID- 16568879
TI  - Beyond the rhetoric: what do we mean by a 'model of care'?
AB  - BACKGROUND: Contemporary health care systems are constantly challenged to revise
      traditional methods of health care delivery. These challenges are multifaceted
      and stem from: (1) novel pharmacological and non-pharmacological treatments; (2)
      changes in consumer demands and expectations; (3) fiscal and resource
      constraints; (4) changes in societal demographics in particular the ageing of
      society; (5) an increasing burden of chronic disease; (6) documentation of
      limitations in traditional health care delivery; (7) increased emphasis on
      transparency, accountability, evidence-based practice (EBP) and clinical
      governance structures; and (8) the increasing cultural diversity of the
      community. These challenges provoke discussion of potential alternative models of
      care, with scant reference to defining what constitutes a model of care. AIM:
      This paper aims to define what is meant by the term 'model of care' and document
      the pragmatic systems and processes necessary to develop, plan, implement and
      evaluate novel models of care delivery. METHODS: Searches of electronic
      databases, the reference lists of published materials, policy documents and the
      Internet were conducted using key words including 'model*', 'framework*',
      'models, theoretical' and 'nursing models, theoretical'. The collated material
      was then analysed and synthesised into this review. RESULTS: This review
      determined that in addition to key conceptual and theoretical perspectives,
      quality improvement theory (eg. collaborative methodology), project management
      methods and change management theory inform both pragmatic and conceptual
      elements of a model of care. Crucial elements in changing health care delivery
      through the development of innovative models of care include the planning,
      development, implementation, evaluation and assessment of the sustainability of
      the new model. Regardless of whether change in health care delivery is attempted
      on a micro basis (eg. ward level) or macro basis (eg. national or state system)
      in order to achieve sustainable, effective and efficient changes a well-planned,
      systematic process is essential.

PMID- 16568880
TI  - Primum non nocere.

PMID- 16568881
TI  - Association of osteonecrosis of the jaws and bisphosphonate pharmacotherapy:
      dental implications.
AB  - Bisphosphonates are drugs of choice in the management of a variety of bone
      disorders including osteoporosis, Paget's disease and bone cancer. Recently there
      have been increasing reports of a possible relationship between bisphosphonate
      therapy and osteonecrosis of the jaws. Osteonecrosis may occur following
      extractions or dental surgery and, in some cases, may appear spontaneously.
      Because of the potentially serious nature of these complications and the failure
      of exposed bone to heal, dentists must be aware of recommended precautions for
      the management of patients taking bisphosphonate medication.

PMID- 16568882
TI  - Bridging the gap: a dental access initiative for Northland children.
AB  - This paper describes a dental access initiative in Northland, New Zealand, to
      investigate the feasibility and benefits of engaging a mobile community dentist
      to accept referrals of children who required treatment beyond the scope of
      practice of dental therapists. The pilot programme aimed to provide equitable and
      timely access to the services of a publicly funded dentist, for children living
      in the more economically-deprived and rural areas of Northland.

PMID- 16568883
TI  - DAI index.

PMID- 16568884
TI  - Seeing or believing? Colour vision loss in dentistry.

PMID- 16568885
TI  - Improving the effectiveness of chlorhexidine.

PMID- 16568886
TI  - Disinfection of dental unit water lines.

PMID- 16568887
TI  - Molecular conjugates.
AB  - Molecular conjugates are nanometer-sized entities consisting of synthetic
      materials (lipids, polycations, targeting agents, and so on) and nucleic acids.
      These composites are delivery vehicles that function to provide the transport of
      nucleic acids to sites of action. Recently, great progress has been made in the
      construction of these nonviral delivery vehicles and the understanding of how
      they function in cells and animals. Here, we review some of the important issues
      in assembling molecular conjugates and understanding their behavior in biological
      fluids, cells, and animals. One of the largest challenges in the field of
      molecular conjugates is how to integrate the components into a workable system
      that exploits the combined attributes of the components without suffering losses
      due to the assembly of the system. We discuss some of the difficulties involved
      in the assembly of a functioning delivery system for in vivo use.

PMID- 16568888
TI  - Plasmid vaccines and therapeutics: from design to applications.
AB  - In the late 1980s, Vical and collaborators discovered that the injection into
      tissues of unformulated plasmid encoding various proteins resulted in the uptake
      of the plasmid by cells and expression of the encoded proteins. After this
      discovery, a period of technological improvements in plasmid delivery and
      expression and in pharmaceutical and manufacturing development was quickly
      followed by a plethora of human clinical trials testing the ability of injected
      plasmid to provide therapeutic benefits. In this chapter, we summarize in detail
      the technologies used in the most recent company-sponsored clinical trials and
      discuss the potential for future improvements in plasmid design, manufacturing,
      delivery, formulation and administration. A generic path for the clinical
      development of plasmid-based products is outlined and then exemplified using a
      case study on the development of a plasmid vaccine from concept to clinical
      trial.

PMID- 16568889
TI  - Nonviral delivery of cancer genetic vaccines.
AB  - The potential use of genetic vaccines to address numerous diseases including
      cancer is promising, but currently unrealized. Here, we review advances in the
      nonviral delivery of antigen-encoded plasmid DNA for the purpose of treating
      cancer through the human immune system, as this disease has drawn the most
      attention in this field to date. Brief overviews of dendritic cell immunobiology
      and the mechanism of immune activation through genetic vaccines set the stage for
      the desirability of delivery technology. Several promising nonviral delivery
      techniques are discussed along with a mention of targeting strategies aimed at
      improving the potency of vaccine formulations. Implications for the future of
      genetic vaccines are also presented.

PMID- 16568890
TI  - Adeno-associated virus as a gene therapy vector: vector development, production
      and clinical applications.
AB  - Adeno-associated virus (AAV) has emerged as an attractive vector for gene
      therapy. AAV vectors have successfully been utilized to promote sustained gene
      expression in a variety of tissues such as muscle, eye, brain, liver, and lung.
      As the significance of AAV as a gene therapy vector has been realized over the
      past years, recent developments in recombinant AAV (rAAV) production and
      purification have revolutionized the AAV field. It is now possible to produce
      high yields of vector (10(12)-10(13) genome-containing particles per mL) that are
      free of contaminating cellular and helper virus proteins. Such vectors have been
      successfully used in preclinical applications in animal models such as those of
      hemophilia, lysosomal storage diseases and vision deficiency, all of which have
      shown therapeutic benefits from rAAV treatment. Clinical trials using rAAV2 for
      the treatment of hemophilia B, cystic fibrosis, alpha-1-antitrypsin deficiency,
      and Canavan disease have begun, and reports from these phase I trials support the
      safety seen in preclinical trials. Eventually, tissue-specific vectors that can
      potentially evade the immune system will be required to optimize success in gene
      therapy. In recent years, this has led to the development of retargeted rAAV2
      vectors and the identification and characterization of new serotypes from human
      and nonhuman primates that could potentially achieve these goals. AAV virologists
      and gene therapists alike have just begun to scratch the surface in terms of the
      utility of this small virus in a clinical setting. In this chapter, we will
      provide a comprehensive overview of the recent advances in rAAV vector production
      and purification, vector development, and clinical applications.

PMID- 16568891
TI  - Advanced targeting strategies for murine retroviral and adeno-associated viral
      vectors.
AB  - Targeted gene delivery involves broadening viral tropism to infect previously
      nonpermissive cells, replacing viral tropism to infect a target cell exclusively,
      or stealthing the vector against nonspecific interactions with host cells and
      proteins. These approaches offer the potential advantages of enhanced therapeutic
      effects, reduced side effects, lowered dosages, and enhanced therapeutic
      economics. This review will discuss a variety of targeting strategies, both
      genetic and nongenetic, for re-engineering the tropism of two representative
      enveloped and nonenveloped viruses, murine retrovirus and adeno-associated virus.
      Basic advances in understanding the structural biology and virology of the parent
      viruses have aided rational design efforts to engineer novel properties into the
      viral attachment proteins. Furthermore, even in the absence of basic, mechanistic
      knowledge of viral function, high-throughput library and directed evolution
      approaches can yield significant improvements in vector function. These two
      complementary strategies offer the potential to gain enhanced molecular control
      over vector properties and overcome challenges in generating high titer,
      stealthy, retargeted vectors.

PMID- 16568892
TI  - Lentiviral vectors.
AB  - We review the use of lentiviral vectors in current human gene therapy
      applications that involve genetic modification of nondividing tissues with
      integrated transgenes. Safety issues, including insertional mutagenesis and
      replication-competent retroviruses, are discussed. Innate cellular defenses
      against retroviruses and their implications for human gene therapy with different
      lentiviral vectors are also addressed.

PMID- 16568893
TI  - Production and formulation of adenovirus vectors.
AB  - Adenovirus vectors have attracted considerable interest over the past decade,
      with ongoing clinical development programs for applications ranging from
      replacement therapy for protein deficiencies to cancer therapeutics to
      prophylactic vaccines. Consequently, considerable product, process, analytical,
      and formulation development has been undertaken to support these programs. For
      example, "gutless" vectors have been developed in order to improve gene transfer
      capacity and durability of expression; new cell lines have been developed to
      minimize recombination events; production conditions have been optimized to
      improve volumetric productivities; analytical techniques and scaleable
      purification processes have advanced towards the goal of purified adenovirus
      becoming a "well-characterized biological"; and liquid formulations have been
      developed which maintain virus infectivity at 2-8 degrees C for over 18 months.
      These and other advances in the production of adenovirus vectors are discussed in
      detail in this review. In addition, the needs for the next decade are
      highlighted.

PMID- 16568894
TI  - What is a quasispecies?
AB  - The concept of the quasispecies as a society formed from a clone of an asexually
      reproducing organism is reviewed. A broad spectrum of mutants is generated that
      compete one with another. Eventually a steady state is formed where each mutant
      type is represented according to its fitness and its formation by mutation. This
      quasispecies has a defined wild type sequence, which is the weighted average of
      all genotypes present. The quasispecies concept has been shown to affect the
      pathway of evolution and has been studied on RNA viruses which have a
      particularly high mutation rate. They (and possibly the majority of other
      species) operate close to the error threshold that allows maximum exploration of
      sequence space while conserving the information content of the genotype. The
      consequences of the quasispecies concept for the new 'evolutionary technology'
      are discussed.

PMID- 16568895
TI  - Quasispecies in time-dependent environments.
AB  - In recent years, quasispecies theory in time-dependent (that is, dynamically
      changing) environments has made dramatic progress. Several groups have addressed
      questions such as how the time scale of the changes affect viral adaptation and
      quasispecies formation, how environmental changes affect the optimal mutation
      rate, or how virus and host co-evolve. Here, we review these recent developments,
      and give a nonmathematical introduction to the most important concepts and
      results of quasispecies theory in time-dependent environments. We also compare
      the theoretical results with results from evolution experiments that expose
      viruses to successive regimes of replication in two or more different hosts.

PMID- 16568896
TI  - Viruses as quasispecies: biological implications.
AB  - During viral infections, the complex and dynamic distributions of variants,
      termed viral quasispecies, play a key role in the adaptability of viruses to
      changing environments and the fate of the population as a whole. Mutant spectra
      are continuously and avoidably generated during RNA genome replication, and they
      are not just a by-product of error-prone replication, devoid of biological
      relevance. On the contrary, current evidence indicates that mutant spectra
      contribute to viral pathogenesis, can modulate the expression of phenotypic
      traits by subpopulations of viruses, can include memory genomes that reflect the
      past evolutionary history of the viral lineage, and, furthermore, can participate
      in viral extinction through lethal mutagenesis. Also, mutant spectra are the
      target on which selection and random drift act to shape the long-term evolution
      of viruses. The biological relevance of mutant spectra is the central topic of
      this chapter.

PMID- 16568897
TI  - Virus fitness: concept, quantification, and application to HIV population
      dynamics.
AB  - Viral fitness has been broadly studied during the past three decades, mainly to
      test evolutionary models and population theories difficult to analyze and
      interpret with more complex organisms. More recent studies, however, are focused
      in the role of fitness on viral transmission, pathogenesis, and drug resistance.
      Here, we used human immunodeficiency virus (HIV) as one of the most relevant
      models to evaluate the importance of viral quasispecies and fitness in HIV
      evolution, population dynamics, disease progression, and potential clinical
      implications.

PMID- 16568898
TI  - Population bottlenecks in quasispecies dynamics.
AB  - The characteristics of natural populations result from different stochastic and
      deterministic processes that include reproduction with error, selection, and
      genetic drift. In particular, population fluctuations constitute a stochastic
      process that may play a very relevant role in shaping the structure of
      populations. For example, it is expected that small asexual populations will
      accumulate mutations at a higher rate than larger ones. As a consequence, in any
      population the fixation of mutations is accelerated when environmental conditions
      cause population bottlenecks. Bottlenecks have been relatively frequent in the
      history of life and it is generally accepted that they are highly relevant for
      speciation. Although population bottlenecks can occur in any species, their
      effects are more noticeable in organisms that form large and heterogeneous
      populations, such as RNA viral quasispecies. Bottlenecks can also positively
      select and isolate particles that still keep the ability to infect cells from a
      disorganized population created by crossing the error threshold.

PMID- 16568899
TI  - Evolutionary dynamics of HIV-1 and the control of AIDS.
AB  - Human immunodeficiency viruses (HIV) have exhibited an extraordinary capacity for
      genetic change, exploring new evolutionary space after each transmission to a new
      host. This presents a great challenge to the prevention and management of HIV-1
      infection. At the same time, the relentless diversification of HIV-1, developing
      as it does under the constraints imposed by the human immune system and other
      selective forces, contains within it information useful for understanding HIV
      epidemiology and pathogenesis. Comparing the sheer mutational potential of HIV
      with actual data representing viral lineages that can survive selection suggests
      that HIV does not have unlimited capacity for change. Rather, clinical and
      bioinformatic data suggest that, even in the most diverse gene of the most highly
      variable organism, natural selection places severe limits on the portion of amino
      acid sequence space that ensures viability. This suggests some optimism for those
      attempting to identify sets of antigens that can generate effective humoral and
      cellular immune responses against HIV.

PMID- 16568900
TI  - Evolution of virulence in picornaviruses.
AB  - The Picornaviridae encompass many positive-strand RNA viruses, all of which share
      a generally similar genome design and capsid structure, but which induce quite
      diverse diseases in humans and other animals. Picornavirus strains of the same
      serotype have been shown to express different virulence (or pathogenic)
      phenotypes when studied in animal models, demonstrating that key elements of
      pathogenesis reside in the viral genome. However, the genetics that determine the
      virulence phenotype of any picornavirus are poorly understood. Picornaviruses do
      not have virulence genes per se, but the design ofthe capsid andhow it interacts
      with the virus receptor expressed on the host cell surface, specific sequences
      within the nontranslated regions of the viral genome, as well as coding sequences
      that result in different protein sequences may all have a part in determining the
      virulence phenotype. Virulence may be better understood as a continuum from an
      apparent inability to induce disease to the ability to cause severe pathogenic
      changes. Ultimately, the ability of a picornavirus to induce disease depends upon
      viral genetics and how they are modulated by the host environment.

PMID- 16568901
TI  - Molecular mechanisms of poliovirus variation and evolution.
AB  - Replication of poliovirus RNA is accomplished by the error-prone viral RNA
      dependent RNA polymerase and hence is accompanied by numerous mutations. In
      addition, genetic errors may be introduced by nonreplicative mechanisms.
      Resulting variability is manifested by point mutations and genomic rearrangements
      (e.g., deletions, insertions and recombination). After description of basic
      mechanisms underlying this variability, the review focuses on regularities of
      poliovirus evolution (mutation fixation) in tissue cultures, human organisms and
      populations.

PMID- 16568902
TI  - Hepatitis C virus population dynamics during infection.
AB  - Hepatitis C virus (HCV) behaves as an evolving viral quasispecies in its
      continuously changing environment. The study of HCV quasispecies population
      dynamics in experimental models and infected patients can provide useful
      information on factors involved in the HCV life cycle and pathogenicity. HCV
      quasispecies variability also has therapeutic implications, as the continuous
      generation and selection of fitter or truly resistant variants can allow the
      virus to escape control by antiviral drugs.

PMID- 16568903
TI  - Evolutionary influences in arboviral disease.
AB  - Arthropod-borne viruses (arboviruses) generally require horizontal transmission
      by arthropod vectors among vertebrate hosts for their natural maintenance. This
      requirement for alternate replication in disparate hosts places unusual
      evolutionary constraints on these viruses, which have probably limited the
      evolution of arboviruses to only a few families of RNA viruses (Togaviridae,
      Flaviviridae, Bunyaviridae, Rhabdoviridae, Reoviridae, and Orthomyxoviridae) and
      a single DNA virus. Phylogenetic studies have suggested the dominance of
      purifying selection in the evolution of arboviruses, consistent with constraints
      imposed by differing replication environments and requirements in arthropod and
      vertebrate hosts. Molecular genetic studies of alphaviruses and flaviviruses have
      also identified several mutations that effect differentially the replication in
      vertebrate and mosquito cells, consistent with the view that arboviruses must
      adopt compromise fitness characteristics for each host. More recently, evidence
      of positive selection has also been obtained from these studies. However,
      experimental model systems employing arthropod and vertebrate cell cultures have
      yielded conflicting conclusions on the effect of alternating host infections,
      with host specialization inconsistently resulting in fitness gains or losses in
      the bypassed host cells. Further studies using in vivo systems to study
      experimental arbovirus evolution are critical to understanding and predicting
      disease emergence, which often results from virus adaptation to new vectors or
      amplification hosts. Reverse genetic technologies that are now available for most
      arbovirus groups should be exploited to test assumptions and hypotheses derived
      from retrospective phylogenetic approaches.

PMID- 16568904
TI  - Arenavirus diversity and evolution: quasispecies in vivo.
AB  - Arenaviruses exist as viral quasispecies due to the high mutation rates of the
      low-fidelity viral RNA-dependent RNA polymerase (RdRp). This genomic
      heterogeneity is advantageous to the population, allowing for adaptation to
      rapidly changing environments that present varying types and degrees of selective
      pressure. The significant variation in biological properties observed among
      lymphocytic choriomeningitis virus (LCMV) strains, the prototypic arenavirus,
      indicates to what extent a quasis-pecies dynamics may play a role in arenavirus
      adaptability and pathogenesis. Several aspects of arenavirus variability and its
      contribution to pathogenesis will be discussed.

PMID- 16568905
TI  - Mutant clouds and occupation of sequence space in plant RNA viruses.
AB  - In nature, RNA viruses of plants often must adapt to ever-changing environments
      in the form of frequent host switches. This would favor a highly diverse
      population for transmission. However, most viruses that have been studied have
      been viruses of monocultural crops. In crop viruses, the mutation frequency of
      individual viral quasispecies varies greatly, both in experiment evolution
      studies and in populations of viruses within single field plants. There is some
      correlation between host range and mutation frequency in experimental evolution
      studies, but few viruses have been examined at the individual quasispecies level.
      Many questions about the nature of plant RNA virus populations and factors that
      affect the effective population sizes, such as genetic bottlenecks and postive
      and negative selection, have only begun to be studied. Many more analyses are
      required before generalized patterns can be determined.

PMID- 16568906
TI  - Parvovirus variation for disease: a difference with RNA viruses?
AB  - The Parvoviridae, a family of viruses with single-stranded DNA genomes widely
      spread from invertebrates to mammal and human hosts, display a remarkable
      evolutionary capacity uncommon in DNA genomes. Parvovirus populations show high
      genetic heterogeneity and large population sizes resembling the quasispecies
      found in RNA viruses. These viruses multiply in proliferating cells, causing
      acute, persistent or latent infections relying in the immunocompetence and
      developmental stage of the hosts. Some parvovirus populations in natural
      settings, such as carnivore autonomous parvoviruses or primate adeno associated
      virus, show a high degree of genetic heterogeneity. However, other parvoviruses
      such as the pathogenic B19 human erythrovirus or the porcine parvovirus, show
      little genetic variation, indicating different virus-host relationships. The
      Parvoviridae evolutionary potential in mammal infections has been modeled in the
      experimental system formed by the immunodeficient scid mouse infected by the
      minute virus of mice (MVM) under distinct immune and adaptive pressures. The
      sequence of viral genomes (close to 10(5) nucleotides) in emerging MVM pathogenic
      populations present in the organs of 26 mice showed consensus sequences not
      representing the complex distribution of viral clones and a high genetic
      heterogeneity (average mutation frequency 8.3 x 10(-4) substitutions/nt
      accumulated over 2-3 months). Specific amino acid changes, selected at a rate up
      to 1% in the capsid and in the NS2 nonstructural protein, endowed these viruses
      with new tropism and increased fitness. Further molecular analysis supported the
      notion that, in addition to immune pressures, the affinity of molecular
      interactions with cellular targets, as the Crml nuclear export receptor or the
      primary capsid receptor, as well as the adaptation to tissues enriched in
      proliferating cells, are major selective factors in the rapid parvovirus
      evolutionary dynamics.

PMID- 16568907
TI  - Transitions in understanding of RNA viruses: a historical perspective.
AB  - This chapter documents that RNA viruses have been known for over a century to be
      genetically variable. In recent decades, genetic and molecular analyses
      demonstrate that they form RNA quasispecies populations; the most rapidly
      mutating, highly variable and genetically versatile life forms on earth. Their
      enormous populations, rapid replication and extreme genetic plasticity can allow
      rates of evolution that exceed those of their eukaryotic host populations by
      millions-fold.

PMID- 16568908
TI  - Functional neuroanatomy of pain.
AB  - Pain is an unpleasant but important biological signal for danger. Nociception is
      necessary for survival and for maintaining the integrity of the organism in a
      potentially hostile environment. Pain is induced by noxious stimuli that act on a
      complex pain sensory apparatus. However, chronic pain no longer affords a
      protective role, but can become a ruining disease itself, termed "neuropathic
      pain". This contribution throws light on the complex machinery of pain
      processing, from the perspective of the connections between key structures that
      are necessary for a profound understanding of the phenomenon of pain.

PMID- 16568909
TI  - Stepping up to Head Start--creating the perfect partnership.

PMID- 16568910
TI  - Conscious sedation and special needs patients revisited.

PMID- 16568911
TI  - Conscious sedation and special needs patients revisited.

PMID- 16568912
TI  - Shear bond strength of pit-and-fissure sealants to saliva-contaminated and
      noncontaminated enamel.
AB  - PURPOSE: The purpose of this study was to investigate the shear bond strength of
      2 resin-based pit-and-fissure sealants--Clinpro and Fluroshield--to saliva
      contaminated and noncontaminated enamel. METHODS: Forty buccal halves of
      permanent molar crowns were individually embedded in polyester resin and ground
      with wet silicone carbide papers to obtain flat enamel surfaces. The specimens
      were randomly assigned to 2 groups: (A) without contamination; and (B)
      contaminated with 0.01 ml of fresh human saliva. Each group was divided into 2
      subgroups (N=10), according to the sealant applied: (1) Clinpro; and (2)
      Fluroshield. Shear bond strength was tested at a crosshead speed of 0.5 mm/min.
      Failure mode was assessed. RESULTS: Means (MPa) were: (1) A1=7.66 +/- 3.12;
      A2=12.39 +/- 4.34; (2) B1=5.05 +/- 1.44; B2=10.44 +/- 2.35. Data were submitted
      to analysis of variance and Scheffe's statistical test (P<.05). There was a
      statistically significant difference (P<.05) between both the sealants and the
      experimental conditions analyzed. Fluroshield provided higher bond strength and
      was different from Clinpro (P<.05) in the absence of contamination. Within the
      saliva-contaminated group, however, no statistically significant difference
      (P>.05) was observed between the tested materials. CONCLUSIONS: It may be
      concluded that, under dry conditions, the filled pit-and-fissure sealant
      (Fluroshield) yielded better bonding performance. Salivary contamination
      undermined the adhesion of both materials to enamel and resulted in lower bond
      strengths.

PMID- 16568913
TI  - Dubowitz syndrome: report of a case with emphasis on the oral features.
AB  - Dubowitz syndrome is a rare condition in which the affected individual presents
      with dysmorphic facial features and manifests growth retardation. Although the
      condition is well reported in the medical literature, the dental manifestations
      have not been discussed in great detail. Some of the dental features reported
      include macrodontia, hypodontia, delayed eruption, and midline diastema. The
      purpose of this case report was to describe a young Chinese patient with Dubowitz
      syndrome with specific oral features.

PMID- 16568914
TI  - Degloving injury of the mandibular mucosa following an extreme sport accident: a
      case report.
AB  - The increasing popularity of high-risk extreme sports such as acrobatic biking,
      mountain biking, skateboarding, or rollerblading is becoming a notable cause of
      maxillofacial injuries. Dentists should, therefore, be familiar with the
      presentation and management of uncommon maxillofacial injuries as a result of
      these extreme sports. The purpose of this article was to detail a case report of
      a 7-year-old male with a degloving injury of the mandibular mucosa following an
      extreme sport accident and to present a description of the patient's
      multidisciplinary management and follow-up.

PMID- 16568915
TI  - Acrylic artificial fingernail embedded in the palate of an 11-month-old: a case
      report.
AB  - Foreign bodies found embedded in the oral cavity have been reported in the
      literature. The purpose of this case report was to document embedding of an
      acrylic artificial fingernail in the palate of an 11-month-old. As the use of
      artificial acrylic nails increases, this case report is also meant to alert oral
      health professionals as to what may become a more common occurrence.

PMID- 16568916
TI  - Glass fiber-reinforced composite resin as fixed space maintainers in children: 12
      month clinical follow-up.
AB  - PURPOSE: The purpose of this clinical evaluation was to assess fixed space
      maintainers for child patients whose missing primary molars were replaced with
      space maintainers made with everStick during a 12-month follow-up period.
      EverStick is a semi-manufactured product made of glass fibers, thermoplastic
      polymer, and light-curing resin matrix for reinforcing the dental polymer.
      METHODS: Twenty-three clinical cases presented in this paper were evaluated in
      the Department of Pediatric Dentistry, Marmara University, Istanbul, Turkey.
      EverStick was used as part of a space maintainer on occasions where 1 or 2 teeth
      were lost in either the maxillary or mandibular arch. RESULTS: This study showed
      that the glass fiber-reinforced composite resin space maintainers functioned well
      during a mid-term evaluation. CONCLUSIONS: Clinical advantages of everStick
      include: (1) cost and time savings; (2) no need for a cast model; (3) no second
      visit; (4) easy to apply; (5) reliable adhesive bonding; (6) no metal allergy;
      (7) easy to clean; (8) natural feel; and (9) esthetically desirable.

PMID- 16568917
TI  - Development of a novel orofacial motor function assessment scale for children
      with cerebral palsy.
AB  - PURPOSE: The aim of this study was to develop the orofacial motor function
      assessment scale (OFMFAS) and appraise its performance in terms of validity and
      reliability in a cohort of 116 cerebral palsy patients. METHODS: The scale was
      developed according to a process derived from the theory of measurement and scale
      development previously described in the dental literature. The final version of
      the OFMFAS comprises 13 items that have 30 subitems. Results were statistically
      analyzed by Bland-Altman for: (1) intrarater consistency; (2) kappa coefficient
      for inter-rater agreement; and (3) Cronbach alpha for internal consistency
      reliability. RESULTS: The majority of OFMFAS items showed a very good agreement
      between the raters (K>0.75). Cronbach alpha for the 13-item scale was 0.93,
      indicating excellent internal consistency reliability. CONCLUSION: This study
      shows that the oralfacial motor function assessment scale is the first
      statistically-based scale for the quantitative assessment of oral-motor skills in
      cerebral palsy children. It is an easy-to-use, accurate, and valid method of
      assessment.

PMID- 16568918
TI  - Quality of anesthesia for the maxillary primary anterior segment in pediatric
      patients: comparison of the P-ASA nerve block using CompuMed delivery system vs
      traditional supraperiosteal injections.
AB  - PURPOSE: The purpose of this study was to compare the quality of 2 injection
      techniques to anesthetize the maxillary primary anterior segment by applying
      either the palatal approach anterior superior alveolar nerve block (P-ASA)
      utilizing a computer-controlled injection device (CompuMed with the Wand
      handpiece) or traditional multiple supraperiosteal (TMS) injections with a hand
      operated syringe. Depth and duration of anesthesia was assessed by the number of
      disruptive behaviors 20 minutes following injection. METHODS: Twenty-one
      preschoolers aged 3 to 5 years, who required pulp tissue removal with subsequent
      crown placement and/or extraction of at least 2 teeth in the maxillary incisor
      segment on opposite sides of the midline, participated in this study. They were
      randomly assigned to either the P-ASA or the TMS injection group. The procedure
      was separated into 3 segments: (1) the injection; (2) overall procedure; and (3)
      painful event. Each segment was scored for disruptive behaviors (body movements,
      crying, restraint, or dentist interference) using an established scale. Scores
      were analyzed via analysis of variance for significance. RESULTS: During
      injection, disruptive behaviors occurred significantly less in the P-ASA group
      than in the TMS group. No significant differences were found between the 2 groups
      for the overall procedure and the painful event segments. CONCLUSION: Whereas
      anesthetic solution delivery with CompuMed system caused significantly less
      disruptive behavior during the injection phase, both methods seem to provide a
      comparable quality of anesthesia for the maxillary primary incisor segment 20
      minutes after deposition of the anesthetic solution.

PMID- 16568919
TI  - Recovery from medical errors: the critical care nursing safety net.
AB  - BACKGROUND: Safety initiatives have primarily focused on physicians despite the
      fact that nurses provide the majority of direct inpatient care. Patient
      surveillance and preventing errors from harming patients represent essential
      nursing responsibilities but have received relatively little study. METHODS: The
      study was conducted between July 2003 and July 2004 in a 10-bed academic coronary
      care unit. Direct observation of nursing care and solicited and institutional
      incident reports were used to find potential incidents. Two physician reviewers
      rated incidents as to the presence, preventability, and potential severity of
      harm of errors and associated factors. RESULTS: Overall data were collected for
      147 days, including 150 hours of direct observation. One hundred forty-two
      recovered medical errors were found, including 61% (86/142) during direct
      observations. Most errors (69%; 98/142) were intercepted before reaching the
      patients. Errors that reached patients included 13% that were mitigated before
      resulting in harm and 18% that were ameliorated before more severe harm could
      occur. DISCUSSION: Protecting patients from the potentially dangerous
      consequences of medical errors is one of the many ways critical care nurses
      improve patient safety. Interventions designed to increase the ability of nurses
      to recover and promptly report errors have the potential to improve patient
      outcomes.

PMID- 16568920
TI  - How many hospital pharmacy medication dispensing errors go undetected?
AB  - BACKGROUND: Hospital pharmacies dispense large numbers of medication doses for
      hospitalized patients. A study was conducted at an academic tertiary care
      hospital to characterize the incidence and severity of medication dispensing
      errors in a hospital pharmacy. METHODS: Direct observation of dispensing
      processes was undertaken to determine presence of errors with review by a
      physician panel to determine severity. RESULTS: A total of 140,755 medication
      doses filled by pharmacy technicians were observed during a seven-month period,
      and 3.6% (5075) contalned errors. The hospital pharmacist detected only 79% of
      these errors during routine verification; thus, 0.75% of doses filled would have
      left the phannacy with undetected errors. Overall, 23.5% of undetected errors
      were potential adverse drug events (ADEs), of which 28% were serious and 0.8%
      were life threatening. The most common potential ADEs were incorrect medications
      (36%), incorrect strength (35%), and incorrect dosage form (21%). DISCUSSION:
      Given the volume of medications dispensed, even a low rate of drug distribution
      process translates into a large number of errors with potential to harm patients.
      Pharmacy distribution systems require further process redesign to achieve the
      highest possible level of safety and reliability.

PMID- 16568921
TI  - Quality improvement in Medicaid managed care: Experience of the best clinical and
      administrative practices initiative.
AB  - BACKGROUND: The Best Clinical and Administrative Practices (BCAP) initiative is
      part of the Medicaid Managed Care Program (MMCP) operated by the Center for
      Health Care Strategies. Work groups of 10-12 plans addressed quality of care in
      designated areas. METHODS AND INFORMATION SOURCES: The assessment of BCAP was
      part of a larger MMCP program evaluation funded by the Robert Wood Johnson
      Foundation. Case studies were developed for four BCAPs that focused respectively
      on improving birth outcomes, preventive care for children, asthma care, and care
      for adults with chronic illnesses or disabilities. They were based on document
      review and semistructured interviews. Medicaid managed care plans nationwide were
      also surveyed. FINDINGS: BCAP participants were overwhelmingly risk-based managed
      care plans whose enrollment was dominated by Medicaid. Participants said BCAP
      helped them enhance the way they approach quality improvement. As a result of
      work group participation, most plans made changes in their delivery of care, and
      more than half sustained and continued to build on these changes after the work
      group ended. DISCUSSION: BCAP participation helped Medicaid plans change the way
      they think about quality improvement and take sustainable steps to improve
      quality; the ultimate impact may be stronger once plans become more sophisticated
      users of such techniques.

PMID- 16568922
TI  - Modifying the universal protocol for effective delivery of perioperative
      pronphylactic antibiotic.

PMID- 16568923
TI  - Monitoring patient safety in health care: building the case for surrogate
      measures.
AB  - BACKGROUND: Objective measurements are notably lacking for many adverse events in
      health care. A new approach to monitoring such events is based on the experience
      in measuring hospital-associated infections. DEVELOPING OBJECTIVE AND UNIVERSAL
      MEASURES: An essential tenet of the current goal of surveillance-focusing only on
      rigorously confirmed adverse events-is neither necessary nor achievable across
      the entire health care system. Efforts should be directed instead to creating
      objective measures of quality of care and of outcomes that can be used by all
      health care facilities. Adopting objective measures would be easier if health
      care was open to surrogate measures of important outcomes. Surrogate measures of
      interest for infection surveillance are used to identify objective, readily
      ascertained events that are sufficiently correlated with infections to provide
      useful information about organizations' infection rates. For example, the
      surgical site infection rate following coronary artery bypass appears to
      correlate closely enough with the proportion of patients who receive extended
      courses of inpatient antibiotics to be a useful indicator of a hospital's
      outcomes for the procedure. CONCLUSION: Developing clinically relevant process or
      surrogate measures that clinicians would use to improve patient outcomes is
      essential. These measures could be relevant not only to hospital-acquired
      infections but other health care-related adverse events that are relatively
      common yet require substantial resources to identify.

PMID- 16568924
TI  - A practical tool to learn from defects in patient care.

PMID- 16568925
TI  - Exploring assumptions about teams.

PMID- 16568926
TI  - Transforming the accreditation of health care management education.
AB  - Recognizing the considerable changes occurring over recent years in health care,
      the Accrediting Commission on Education for Health Services Administration
      (ACEHSA) sought to remake itself to become a more vital participant in the field.
      This article reports the rationale, objectives, and process pursued by ACEHSA as
      it underwent this transformation and adopted a new name: Commission on
      Accreditation of Healthcare Management Education (CAHME). This paper features the
      planning document adopted to lead CAHME through the future. It also highlights
      actions taken to date and subsequent steps planned.

PMID- 16568927
TI  - Long-term care over an uncertain future: what can current retirees expect?
AB  - The leading edge of the baby boom generation is nearing retirement and facing
      uncertainty about its need for long-term care (LTC). Using a microsimulation
      model, this analysis projected that people currently turning age 65 will need LTC
      for three years on average. An important share of needed care will be covered by
      public programs and some private insurance, but much of the care will be an
      uninsured private responsibility of individuals and their families--a
      responsibility that will be distributed unequally. While over a third of those
      now turning 65 are projected to never receive family care, three out of 10 will
      rely on family care for more than two years. Similarly, half of people turning 65
      will have no private out-of-pocket expenditures for LTC, while more than one in
      20 are projected to spend $100,000 or more of their own money (in present
      discounted value). Policy debate that focuses only on income security and acute
      care--and the corresponding Social Security and Medicare programs--misses the
      third, largely private, risk that retirees face: that of needing LTC.

PMID- 16568928
TI  - Medicare's prospective payment system for skilled nursing facilities: effects on
      staffing and quality of care.
AB  - In 1998, Medicare began phasing in a new prospective payment system (PPS) for
      skilled nursing facilities (SNFs). This paper measures facility-level changes in
      nurse staffing and quality at freestanding SNFs from 1997 (pre-PPS) to 2001 (post
      PPS). Findings show a positive but small association between changes in payment
      levels and changes in nurse staffing. Among for-profits, the elimination of cost
      reimbursement is associated with a large drop in nurse staffing. Additionally,
      the elimination of cost reimbursement is associated with worsening in one of four
      measures of quality of care; however, the quality results are not statistically
      robust.

PMID- 16568929
TI  - Health insurance reform and HMO penetration in the small group market.
AB  - This study uses data from several national employer surveys conducted between the
      late 1980s and the mid-1990s to investigate the effect of state-level
      underwriting reforms on HMO penetration in the small group health insurance
      market. We identify reform effects by exploiting cross-state variation in the
      timing and content of reform legislation and by using mid-sized and large
      employers, which were not affected by the legislation, as within-state control
      groups. While it is difficult to disentangle the effect of state reforms from
      other factors affecting HMO penetration in the small group markets, the results
      suggest a positive relationship between insurance market regulations and HMO
      penetration.

PMID- 16568930
TI  - Is the individual market more than a bridge market? An analysis of disenrollment
      decisions.
AB  - The individual insurance market is perceived by many to provide primarily
      transition coverage, but there is limited research about how long people stay in
      this market and what affects their disenrollment decisions. We examine these
      issues using administrative records and survey data for those enrolled in the
      individual market in California. We conclude that there is less turnover in this
      market than is commonly believed. We find that economic factors and coverage
      characteristics are important in the decision to disenroll, but that perceptions
      about insurance and the health care system also affect this decision.

PMID- 16568931
TI  - New cardiovascular drugs: patterns of use and association with non-drug health
      expenditures.
AB  - The potential role of new drugs in reducing expenditures for non-drug health
      services has received considerable attention in recent policy debates. We
      estimate expenditure models to determine whether the use of newer drugs to treat
      cardiovascular conditions is associated with lower (or higher) non-drug
      expenditures for these conditions. We fail to substantiate the findings of
      previous research that newer drugs are associated with reductions in non-drug
      expenditures. We find, however, that increases in the number of drugs used, or
      the mix of drugs of different ages, are associated with increased non-drug
      expenditures and find that the number or mix of drugs used are important
      confounders in the estimated association between drug age and non-drug
      expenditures.

PMID- 16568932
TI  - The implications of unmet need for future health care use: findings for a sample
      of disabled Medicaid beneficiaries in New York.
AB  - Using survey data linked with Medicaid claims data, this study examines the
      consequences of unmet need for future health care use for a sample of disabled
      Medicaid beneficiaries in Westchester County, New York. Among other things, we
      find that individuals reporting unmet need in 1999 were more likely to use
      emergency room and hospital care in 2000 than those not reporting unmet need.
      Addressing the barriers to care that underlie unmet need could generate cost
      savings to Medicaid and provide better health outcomes for program beneficiaries.

PMID- 16568933
TI  - Providing senior design students with a clinical perspective.

PMID- 16568934
TI  - A brief introduction to functional MRI.

PMID- 16568935
TI  - Evaluating fMRI preprocessing pipelines.

PMID- 16568936
TI  - Modeling and inference of multisubject fMRI data.

PMID- 16568937
TI  - Using small numbers of subjects in fMRI-based research.
AB  - The preceding speculations may not sound very novel to some ears. Indeed, when I
      started to describe the above ideas to any fMRI researcher who has been involved
      in the field for a substantial number of years, their response is invariably a
      comment to the effect that, "Oh yes, we are doing something like that right now
      in our lab." What I think they mean, of course, is that sometime in the uncertain
      future they might run all their own existing tasks on a few subjects, if they can
      get around to it and if they can find the software for some of those earlier
      tasks. The heart (and hard parts) of the present speculation would be creating a
      repository of (publicly available) interesting tasks and creating software to
      embody neuropsychological models and the associated imaging data. At the risk of
      completely losing my audience, it is the image presented in Isaac Asimov's novel
      Second Foundation for integrating theory and information across many different
      sources that is the true challenge.

PMID- 16568938
TI  - Multivariate statistical analysis in fMRI.

PMID- 16568939
TI  - Surfing the brain.

PMID- 16568940
TI  - Unmixing fMRI with independent component analysis.

PMID- 16568941
TI  - Increasing the effect size in event-related fMRI studies.

PMID- 16568943
TI  - fMRI neuroinformatics.

PMID- 16568942
TI  - Exploratory analysis of brain connectivity with ICA.

PMID- 16568944
TI  - Understanding organizational wrongdoing II.

PMID- 16568945
TI  - Where did the big E come from?

PMID- 16568947
TI  - Nucleosome structure and function.
AB  - It is now widely recognized that the packaging of genomic DNA, together with core
      histones, linker histones, and other functional proteins into chromatin
      profoundly influences nuclear processes such as transcription, replication, DNA
      repair, and recombination. How chromatin structure modulates the expression of
      knowledge encoded in eukaryotic genomes, and how these processes take place
      within the context of a highly complex and compacted genomic chromatin
      environment remains a major unresolved question in biology. Here we review recent
      advances in nucleosome structure and dynamics.

PMID- 16568946
TI  - The role of histone modifications in epigenetic transitions during normal and
      perturbed development.
AB  - Epigenetic mechanisms control eukaryotic development beyond DNA-stored
      information. DNA methylation, histone modifications and variants, nucleosome
      remodeling and noncoding RNAs all contribute to the dynamic make-up of chromatin
      under distinct developmental options. In particular, the great diversity of
      covalent histone tail modifications has been proposed to be ideally suited for
      imparting epigenetic information. While most of the histone tail modifications
      represent transient marks at transcriptionally permissive chromatin, some
      modifications appear more robust at silent chromatin regions, where they index
      repressive epigenetic states with functions also outside transcriptional
      regulation. Under-representation of repressive histone marks could be indicative
      of epigenetic plasticity in stem, young and tumor cells, while committed and
      senescent (old) cells often display increased levels of these more stable
      modifications. Here, we discuss profiles of normal and aberrant histone lysine
      methylation patterns, as they occur during the transition of an embryonic to a
      differentiated cell or in controlled self-renewal vs pro-neoplastic or metastatic
      conditions. Elucidating these histone modification patterns promises to have
      important implications for novel advances in stem cell research, nuclear
      reprogramming and cancer, and may offer novel targets for the combat of tumor
      cells, potentially leading to new diagnostic and therapeutic avenues in human
      biology and disease.

PMID- 16568948
TI  - The role of Snf2-related proteins in cancer.
AB  - Several HDAC inhibitors that exhibit impressive anti-tumour activity are now in
      clinical trials. Proteins that function in the same pathways might also serve as
      valuable therapeutic targets. A subset of histone deacetylase activities are
      found to be physically associated with ATP-dependent remodelling enzymes and may
      assist their function. This raises the possibility that ATP-dependent remodelling
      enzymes should be considered as therapeutic targets. Here some of the links
      between ATP-dependent chromatin remodelling enzymes and cancer are reviewed.

PMID- 16568949
TI  - Imitation switch complexes.
AB  - The imitation switch (ISWI) family of chromatin remodelling ATPases is found in
      organisms ranging from yeast to mammals. ISWI ATPases assemble chromatin and
      slide and space nucleosomes, making the chromatin template fluid and allowing
      appropriate regulation of events such as transcription, DNA replication,
      recombination and repair. The site of action of the ATPases is determined, in
      part by the tissue type in which the enzyme is expressed and in part by the
      nature of the proteins associated with the enzyme. The ISWI complexes are
      generally conserved in composition and function across species. Roles in gene
      expression and DNA replication in heterochromatin, gene activation and repression
      in euchromatin, and functions related to maintaining chromosome architecture are
      associated with different complexes. Defects in ISWI-associated proteins may be
      associated with neurodegenerative disease, anencephaly, William's syndrome and
      melanotic tumours. Finally, the mechanism by which yeast Isw Ib influences gene
      transcription is discussed.

PMID- 16568951
TI  - Polycomb silencing mechanisms and genomic programming.
AB  - Polycomb complexes, best known for their role in the epigenetic silencing of
      homeotic genes, are now known to regulate a large number of functions in
      organisms from flies to man. They control transcription activators, pattern
      forming genes, maintenance of stem cells and are implicated in cell proliferation
      and oncogenesis. Our understanding of Polycomb mechanisms derives principally
      from the study of homeotic genes in Drosophila, where they act in an all-or-none
      fashion to silence expression in inappropriate parts of the organism. This review
      summarizes what has been learned from homeotic genes and examines the possible
      extensions of Polycomb mechanisms to allow for dynamic regulatory behavior and
      the reprogramming of silenced chromatin states.

PMID- 16568950
TI  - How is epigenetic information on chromatin inherited after DNA replication?
AB  - Although most somatic cells have identical genetic information, gene expression
      profiles are quite distinct in each cell type. The gene expression profiles are
      considered to be determined mainly by chromatin-encoded epigenetic information
      that includes histone modifications, histone variants, and factors such as HP1
      and polycomb group proteins that organize higher-ordered chromatin structures. To
      gain insights into how such epigenetic information on chromatin is inherited on
      daughter DNA strands after DNA replication, we have purified the preassembled
      form of histone H3 by immunoaffinity purification. The histone H3 complex
      contains the two histone H3-H4 chaperones CAF1 and ASF1. Surprisingly, the H3
      complex also contains a pair of H3-H4 dimers. This observation is striking
      because histones H3-H4 are known to exist as tetramers in solution. Since
      histones H3-H4 in the predeposition complex exist as a dimer, this raises the
      possibility that the H3-H4 dimer in the complex pairs with a parental H3-H4
      dimer, assembling the de novo-synthesized and parental H3-H4 dimers in the same
      nucleosome. Based on these results, we propose a semi-conservative model of
      nucleosome duplication, which allows for segregation of parental H3-H4 dimers
      with encoded epigenetic information evenly to daughter DNA strands.

PMID- 16568952
TI  - CpG island methylation and histone modifications: biology and clinical
      significance.
AB  - The discovery that drastic changes in DNA methylation and histone modifications
      are common in human tumors has inspired various laboratories and pharmaceutical
      companies to develop and study epigenetic drugs. One of the most promising groups
      of agents is the inhibitors of histone deacetylases (HDACs), which have different
      biochemical and biologic properties but have a single common activity: induction
      of acetylation in histones, the key proteins in nucleosome and chromatin
      structure. HDAC inhibitors may act through the transcriptional reactivation of
      dormant tumor-suppressor genes. However, their pleiotropic nature leaves open the
      possibility that their well-known differentiation, cell-cycle arrest, and
      apoptotic properties are also involved in other functions associated with HDAC
      inhibition. Many phase I clinical trials indicate that HDAC inhibitors appear to
      be well-tolerated drugs. Thus, the field is ready for rigorous biologic and
      clinical scrutiny to validate the therapeutic potential of these drugs. HDAC
      inhibitors, probably in association with classical chemotherapy drugs or in
      combination with DNA-demethylating agents, could be promising drugs for cancer
      patients.

PMID- 16568953
TI  - Histone post-translational modifications regulate transcription and silent
      chromatin in Saccharomyces cerevisiae.
AB  - Regulation of chromatin structure is important for the control of DNA-templated
      processes such as gene expression and silencing, and its dysregulation is
      implicated in diverse developmental and cell proliferative defects such as
      tumorigenesis. Covalent post-translational modifications of histones are one of
      the prominent means to regulate the chromatin structure. Here, we summarize
      findings from our lab and others regarding the interactions between different
      covalent modifications of histones in the budding yeast Saccharomyces cerevisiae.
      First, we describe the effect of histone H3 phosphorylation at residue serine 10
      in transcriptional gene activation, and its histone H3 acetylation dependent and
      independent modes of action and downstream effects on TATA-binding protein (TBP)
      recruitment. Further, we review how ubiquitylation of histone H2B and its
      deubiquitylation by ubiquitin proteases Ubp8 and Ubp10 regulate histone H3
      methylations, and consequently affect co-activator-dependent gene transcription
      and silent chromatin, respectively.

PMID- 16568954
TI  - Histone acetylation-mediated chromatin compaction during mouse spermatogenesis.
AB  - One of the most dramatic chromatin remodelling events takes place during
      mammalian spermatogenesis involving massive incorporation of somatic and testis
      specific histone variants, as well as generalized histone modifications before
      their replacement by new DNA packaging proteins. Our data suggest that the
      induced histone acetylation occurring after meiosis may direct the first steps of
      genome compaction. Indeed, a double bromodomain-containing protein expressed in
      postmeiotic cells, Brdt, shows the extraordinary capacity to specifically
      condense acetylated chromatin in vivo and in vitro. In elongating spermatids,
      Brdt widely co-localizes with acetylated histones before accumulating in
      condensed chromatin domains. These domains preferentially maintain their
      acetylation status until late spermatogenesis. Based on these data, we propose
      that Brdt mediates a general histone acetylation-induced chromatin compaction and
      also maintains differential acetylation of specific regions, and is therefore
      involved in organizing the spermatozoon's genome.

PMID- 16568955
TI  - Role of ubiquitin-like proteins in transcriptional regulation.
AB  - Conjugation of ubiquitin-like proteins (Ubls) to components of the
      transcriptional machinery represents an important mechanism to allow switching
      between different activity states. While ubiquitin modification of transcription
      factors is associated with transcriptional activation, SUMO modification of
      transcription factors is most often associated with transcriptional repression.
      Recent experiments indicate that another Ubl, NEDD8, can also influence
      transcription. One of the characteristics of Ubl modification is that the
      biological consequences of conjugation do not appear proportionate to the small
      fraction of substrate that is modified. The low steady state levels of Ubl
      modified substrates can be attributed to a highly dynamic situation in which
      proteins are conjugated to a particular Ubl only for the modification to be
      removed by Ubl-specific proteases. It therefore appears that an unmodified
      protein with a history of Ubl modification may have different properties from a
      protein that never has been modified. Here the diverse effects of Ubl
      modification are discussed and models proposed to explain Ubl actions.

PMID- 16568957
TI  - Self-assembly of peptide porphyrin complexes: toward the development of smart
      biomaterials.
AB  - The anionic porphyrin, meso-tetrakis(4-sulfonatophenyl)porphine, is found to
      tightly bind to an engineered 14-residue peptide, resulting in induced alpha
      helix formation when mixed in aqueous solutions. The small porphyrin-peptide
      dissociation constant (2 muM) observed is related to the energetics of peptide
      helix formation coupled with electrostatic interactions between the anionic
      porphyrin and cationic residues in the coiled peptide. Analytical
      ultracentrifugation measurements indicate the porphyrin-peptide complexes
      dimerize, probably into a coiled coil, and weakly associate to form even higher
      order structures.

PMID- 16568956
TI  - Interplay of the SUMO and MAP kinase pathways.
AB  - The SUMO modification pathway has been linked with controlling the activity of
      numerous transcriptional regulatory proteins. In the majority of substrates
      studied so far, sumoylation imparts repressive properties. In several cases, part
      of this mechanism has been shown to be due to SUMO-dependent recruitment of
      histone deacetylases (HDACs). This is exemplified by the transcription factor Elk
      1, where HDAC-2 is specifically recruited in response to sumoylation.
      Importantly, activation of the ERK MAP kinase pathway leads to Elk-1
      desumoylation and HDAC loss. Furthermore, PIAS proteins can regulate the
      activities of transcription factors in SUMO-dependent and -independent manners.
      Further links between the MAP kinase pathways and PIAS proteins have been
      uncovered, suggesting a complex interplay been the MAP kinase and SUMO
      modification pathways. Here we discuss the current evidence suggesting links
      between the SUMO and MAP kinase pathways and point to other potential regulatory
      events and how these might be affected in cancer.

PMID- 16568958
TI  - Multifunctional polymeric nanoparticles from diverse bioactive agents.
AB  - We present a rational approach for assembling diverse bioactive agents, such as
      DNA, proteins, and drug molecules, into core-shell multifunctional polymeric
      nanoparticles (PNPs) that can be internalized in human breast cancer cells. Using
      ring-opening metathesis polymerization (ROMP), block copolymers containing small
      molecule drug segments (>50% w/w) and tosylated hexaethylene glycol segments were
      prepared and assembled into PNPs that allowed for the surface conjugation of
      single-stranded DNA sequences and/or tumor-targeting antibodies. The resulting
      antibody-functionalized particles were readily uptaken by breast cancer cells
      that overexpressed the corresponding antigens.

PMID- 16568959
TI  - Polar networks control oligomeric assembly in membranes.
AB  - Polar interactions have a profound influence on membrane stability and structure.
      A membrane-solubilized GCN4 peptide, MS-1, is used to study the impact of polar
      networks. Amide functionalities from amino acid side chains have been shown to
      promote peptide oligomerization, but lacked specificity. Herein, the hydrogen
      bonding interactions of an Asn side chain are coupled with the hydroxyl of Ser or
      Thr to generate a polar network. Analytical ultracentrifugation and fluorescence
      resonance energy transfer studies indicate that a trimer assembly is established
      where each membrane-embedded hydrogen bond contributes 1 kcal mol-1.

PMID- 16568960
TI  - Role of the guanine N1 imino proton in the migration and reaction of radical
      cations in DNA oligomers.
AB  - Oxidation of a guanine nucleobase to its radical cation in DNA oligomers causes
      an increase in the acidity of the N1 imino proton that may lead to its
      spontaneous transfer to N3 of the paired cytosine. This proton transfer is
      suspected of playing an important role in long-distance radical cation hopping in
      DNA and the decisive product-determining role in the reaction of the radical
      cation with H2O or O2. We prepared and investigated DNA oligomers in which
      certain deoxycytidines are replaced by 5-fluoro-2'-deoxycytidines (F5dC). The pKa
      of F5C was determined to be 1.7 units below that of dC, which causes proton
      transfer from the guanine radical cation to be thermodynamically unfavorable.
      Photoinitiated one-electron oxidation of the DNA by UV irradiation of a
      covalently attached anthraquinone derivative introduces a radical cation that
      hops throughout the oligomer and is trapped selectively at GG steps. The
      introduction of F5dC does not affect the efficiency of charge hopping, but it
      significantly reduces the amount of reaction at the GG sites, as revealed by
      subsequent reaction with formamidopyrimidine glycosylase. These findings suggest
      that transfer of the guanine radical cation N1 proton to cytosine does not play a
      significant role in long-range charge transfer, but this process does influence
      the reactions with H2O and/or O2.

PMID- 16568961
TI  - Mechanistic implications in the Morita-Baylis-Hillman alkylation: isolation and
      characterization of an intermediate.
AB  - An intermediate phosphonium salt has never been isolated from the Morita-Baylis
      Hillman (MBH) reaction. Due to the weakly basic counterion produced in the MBH
      alkylation and allylation reactions, the reaction can be stopped after
      electrophilic attack on the zwitterionic enolate and an intermediate isolated.
      Upon analysis of the crystal structure, a trans geometry is observed, suggesting
      that there is no electrostatic interaction between phosphorus and oxygen in the
      zwitterionic enolate that undergoes alkylation, thus giving new mechanistic
      insight into the MBH reaction.

PMID- 16568962
TI  - Superactivation of the botulinum neurotoxin serotype A light chain
      metalloprotease: a new wrinkle in botulinum neurotoxin.
AB  - Small molecules based upon a 2-acylguanidine-5-phenyl thiophene scaffold that can
      activate the light chain metalloprotease of botulinum neurotoxin serotype A (BoNT
      LC/A) by an apparent reduction in Km are reported. On the basis of structure
      activity relationships and the activation profile, one or more molecules of
      activator specifically bind to a defined site on the toxin, causing the observed
      rate enhancement. With the ever-growing clinical uses of BoNT, compounds such as
      those reported here may provide a method for combating the emerging adaptive
      immune responses to BoNT.

PMID- 16568963
TI  - Molecularly imprinted nanoreactors for regioselective huisgen 1,3-dipolar
      cycloaddition reaction.
AB  - A molecularly imprinted polymer has been successfully utilized as nanoreactors
      for Huisgen 1,3-dipolar cycloaddition of azides and alkynes, leading to high
      product regioselectivity and kinetic acceleration. The MIP nanoreactors also
      showed remarkable selectivity toward the reactant structures, so that the "best
      fit" product was mostly amplified during the reaction. In contrast to previously
      reported regioselective MIPs, the present imprinted cavities bind reactants by
      means of only noncovalent molecular interactions, the same as that normally
      involved in biological systems. The results support the concept of drug "cloning"
      that further extends both the anti-idiotypic imprinting and in-cavity synthesis
      approaches into the modern drug discovery area.

PMID- 16568964
TI  - Zn(tbip) (H2tbip= 5-tert-butyl isophthalic acid): a highly stable guest-free
      microporous metal organic framework with unique gas separation capability.
AB  - A novel guest-free metal organic framework (GFMMOF) is synthesized and
      structurally characterized. It contains one-dimensional close-packed open
      channels with a pore diameter of 4.5 A. It demonstrates a remarkable thermal
      stability, a unique ability to separate methanol from dimethyl ether or water,
      and is among the microporous MOFs having the highest adsorbed hydrogen density
      (0.054 g/cm3 at 77 K and 1 atm).

PMID- 16568965
TI  - Fluorophilicity switch by solvation.
AB  - A new type of fluorous distannoxanes, [XRf2SnOSnRf2Y]2 (Rf = C6F13C2H4; X, Y =
      C6F13SO3 (2) and (C6F13SO2)2N, Cl (3)) was prepared successfully as hydrates from
      the reaction of [ClRf2SnOSnRf2Cl]2 with C6F13SO3Ag and (C6F13SO2)2NAg,
      respectively. Despite their high fluorine content (59.85 and 59.27% F), these
      distannoxanes were completely insoluble in fluorocarbons as well as hydrocarbons
      and halo alkanes. In contrast to this, fluorous distannoxanes 2 and 3 were
      soluble in polar organic solvents, such as EtOAc, acetone, and THF. When 2 and 3
      were added to a two-phase mixture of fluorocarbon and EtOAc, the mixture turned
      miscible in proportion to the amount of 2 and 3 added, and finally, the mixture
      turned to a homogeneous solution.

PMID- 16568967
TI  - Living polymerization of alpha-olefins with an alpha-diimine Ni(II) catalyst:
      formation of well-defined ethylene-propylene copolymers through controlled chain
      walking.
AB  - A C2-symmetric Ni(II) catalyst was found to polymerize alpha-olefins with high
      levels of omega,2-regiochemistry. The resulting products are ethylene-propylene
      type copolymers with methylene sequences of precise length between methyl
      branches. Modification of reaction conditions can introduce omega,1-enchainments
      into the polymers which increases the average length of methylene sequences
      between methyl branches.

PMID- 16568966
TI  - Positive homotropic allosteric binding of silver(I) cations in a Schiff base
      oligopyrrolic macrocycle.
AB  - The binuclear silver(I) complex of a Schiff base oligopyrrolic macrocycle was
      prepared in high yield and fully characterized. UV-visible absorption and 1H NMR
      spectroscopic analyses reveal that coordination of Ag(I) cations is subject to a
      strong positive homotropic allosteric effect.

PMID- 16568968
TI  - Self-assembly of bidentate ligands for combinatorial homogeneous catalysis:
      asymmetric rhodium-catalyzed hydrogenation.
AB  - The first chiral ligand library based on self-assembly through complementary
      hydrogen-bonding was realized. From a 10 x 4 ligand library, catalysts that show
      excellent activity and enantioselectivity for the asymmetric rhodium-catalyzed
      hydrogenation have been identified.

PMID- 16568969
TI  - Chemical analysis of norrisolide-induced Golgi vesiculation.
AB  - The chemical origin of the norrisolide-induced irreversible Golgi vesiculation
      was studied using a variety of norrisolide probes. This natural product was found
      to bind to a receptor on the Golgi membranes using the perhydroindane core
      fragment as the recognition element. The acetylated gamma-lactol-gamma-lactone
      side chain of norrisolide is essential for the irreversible Golgi vesiculation
      and can be replaced by other electrophilic motifs without loss of biological
      function. In particular, compound 10 reproduces the cellular phenotype of the
      natural product.

PMID- 16568970
TI  - Negative regulation of a protein tyrosine phosphatase by tyrosine
      phosphorylation.
AB  - The low molecular weight protein tyrosine phosphatase (LMW-PTP) is a ubiquitously
      expressed enzyme with several proposed roles in cell signaling. Previously, two
      tyrosine phosphorylation modifications of LMW-PTP at sites Tyr-131 and Tyr-132 in
      response to growth factor stimulation have been mapped and suggested to stimulate
      LMW-PTP phosphatase activity. Biochemical analysis of tyrosine phosphorylation of
      a tyrosine phosphatase is challenging because of the intrinsic instability of
      these modifications. Here we used expressed protein ligation to site-specifically
      incorporate a phosphotyrosine mimic (phosphonomethylenephenylalanine, Pmp) at the
      Tyr-131 and Tyr-132 positions and measured the catalytic activity of these
      semisynthetic LMW-PTPs. The phosphonate-modified LMW-PTPs were 10- to 23-fold
      less active in dephosphorylating phosphotyrosine peptides derived from the PDGF
      receptor and p190RhoGap, two putative cellular substrates. These findings suggest
      the first example of a tyrosine phosphatase that is inhibited by tyrosine
      phosphorylation and provide a new model for the regulation of LMW-PTP and its
      role in cell adhesion.

PMID- 16568971
TI  - Generation of complex, static solution gradients in microfluidic channels.
AB  - A microfluidic device is used to generate a complex gradient of diffusible
      molecules in a static solution. The gradient is precise and steady both in space
      and in time. This device, made from poly(dimethylsiloxane), consists of three
      layers. The molecules in reservoirs on the top layer diffuse through the flat
      middle layer of hydrogel and reach an equilibrium distribution. Microfluidic
      channels on the bottom layer that are in close contact with the hydrogel contain
      free solution that has concentration gradients based on the gradient in the gel.
      The gradient profile in the channel can be designed to have an arbitrary form
      (within the range of the existing gradient in the hydrogel) by controlling the
      local direction of the channel at each point.

PMID- 16568972
TI  - Chemistry of [Et4N][MoIV(SPh)(PPh3)(mnt)2] as an analogue of dissimilatory
      nitrate reductase with its inactivation on substitution of thiolate by chloride.
AB  - Structural-functional analogue of the reduced site of dissimilatory nitrate
      reductase is synthesized as [Et4N][MoIV(SPh)(PPh3)(mnt)2].CH2Cl2 (1). PPh3 in 1
      is readily dissociated in solution to generate the active site of the reduced
      site of dissimilatory nitrate reductase. This readily reacts with nitrate. The
      nitrate reducing system is characterized by substrate saturation kinetics.
      Oxotransfer to and from substrate has been coupled to produce a catalytic system,
      NO3- + PPh3 --> NO2- + OPPh3, where NO3- is the substrate for dissimilatory
      nitrate reductase. The corresponding chloro complex,
      [Et4N][MoIV(Cl)(PPh3)(mnt)2].CH2Cl2 (2), responds to similar PPh3 dissociation
      but is unable to react with nitrate, showing the indispensable role of thiolate
      coordination for such oxotransfer reaction. This investigation provides the
      initial demonstration of the ligand specificity in a model system similar to
      single point mutation involving site directed mutagenesis in this class of
      molybdoenzymes.

PMID- 16568973
TI  - Imaging adsorbate O-H bond cleavage: methanol on TiO2(110).
AB  - We investigated methanol adsorption and dissociation on bridge-bonded oxygen
      vacancies of the TiO2(110)-(1x1) surface using in situ scanning tunneling
      microscopy. We provide the first direct evidence that methanol dissociates on
      oxygen vacancies via O-H bond scission rather than C-O scission. For CH3OH
      coverages lower than the oxygen vacancy concentration, stationary methoxy
      hydroxyl pairs form. At CH3OH coverages close to the oxygen vacancy concentration
      undissociated mobile CH3OH interacts with methoxy-hydroxyl pairs and facilitates
      the movement of hydroxyl away from the methoxy group.

PMID- 16568974
TI  - DNA-programmed control of photosensitized singlet oxygen production.
AB  - DNA sequence-controlled on-and-off switching of a singlet oxygen sensitizer has
      been developed and demonstrated. The singlet oxygen photosensitizer
      pyropheophorbide-a (P) was attached to a 15-mer nucleotide sequence. A molecule
      that could quench the sensitizer, the so-called "black hole quencher 3" (Q), was
      attached to a complementary nucleotide strand. Upon hybridization of the two
      conjugates, singlet oxygen production from P was completely shut down. Upon the
      addition of a third DNA sequence that can displace and release the P-DNA
      conjugate from the P-Q pair, up to 85% of the singlet oxygen production was
      recovered. This system is a model for a benign drug that becomes active only in
      the presence of a specific targeted nucleotide sequence.

PMID- 16568975
TI  - Printed silver ohmic contacts for high-mobility organic thin-film transistors.
AB  - Oleic acid-stabilized silver nanoparticles prepared by a facile synthesis
      afforded highly conductive elements upon proper annealing. Regioregular
      polythiophene-based thin-film transistors (OTFTs) using source/drain electrodes
      prepared from these silver nanoparticles provided excellent field-effect
      characteristics, despite a significant difference between the work function of
      silver and the HOMO of polythiophene semiconductor. This was attributable to
      conductive doping of the semiconductor interface by residual oleic acid or its
      thermally transformed derivative from the silver electrodes, thus enabling ohmic
      contact formation. This is in sharp contrast to the OTFTs with silver electrodes
      fabricated from both vacuum deposition and oleylamine-stabilized silver
      nanoparticles, which exhibited markedly lower mobility and current on/off ratio,
      a consequence of energetic mismatch of the electrode/semiconductor pairs.

PMID- 16568976
TI  - Synthetic ligands for apo-neocarzinostatin.
AB  - Neocarzinostatin (NCS) is a 1:1 complex of an enediyne chromophore (NCSChrom),
      non-covalently bound to an 11 kDa protein (apoNCS). We are exploring apoNCS as a
      generic protein system for sequestering small molecules for therapeutic
      applications. Here, we disclose a new flavone ligand 1 for apoNCS and present a
      high-resolution NMR structure of this ligand bound to apoNCS. This is the first
      high-resolution structure of a completely non-cognate ligand bound to the apoNCS
      protein. This work provides unambiguous evidence that a completely new class of
      ligand can bind specifically to apoNCS. Furthermore, the mode of binding is
      different than that of the naphthoate-based ligands, and for such a simple
      hydrophobic compound, the new ligand surprisingly binds specifically. This work
      indicates that apo-Neocarzinostatin has multiple selective and distinct binding
      modes for small-molecule cargo.

PMID- 16568978
TI  - Bond-forming reactions of molecular dications as a new route to polyaromatic
      hydrocarbons.
AB  - Mass-selected CmHn2+ dications of medium size (m = 6-14, n = 6-10) undergo bond
      forming reactions in the presence of acetylene with Cm+2Hn2+ + H2 as the major
      product channel. These unprecedented reactions of organic dications offer a
      feasible route for the formation of polycyclic aromatic hydrocarbons under
      extreme conditions, such as in interstellar clouds.

PMID- 16568977
TI  - Metal-enhanced fluorescence-based RNA sensing.
AB  - In this communication, we present the proof-of-principle of a new RNA sensing
      technique, based on metal-enhanced fluorescence, which may improve the potential
      of solid substrate-based RNA capture assays. In this regard, the detection of RNA
      is accomplished by annealing a target RNA tagged with a fluorophore to a DNA
      anchor probe in a single step on a solid surface, where the fluorescence signal
      is enhanced by silver nanoparticles. Furthermore, the proposed method is highly
      amenable to high-throughput screening applications and is capable of detecting
      less than 25 fmol of RNA at a signal-to-noise ratio greater than 20, in several
      hours compared to that of reverse transcription-PCR at >24 h.

PMID- 16568979
TI  - Electrophilic C-H activation at Cp*Ir: ancillary-ligand control of the mechanism
      of C-H activation.
AB  - Density functional calculations on the low-temperature cyclometalation of
      dimethylbenzylamine with [IrCl2Cp*]2/NaOAc have characterized a novel
      electrophilic activation pathway for C-H bond activation. C-H activation occurs
      from [Ir(DMBA-H)(kappa2-OAc)Cp*]+, and OAc plays a central role in determining
      the barrier for reaction. Dissociation of the proximal OAc arm sets up a facile
      intramolecular deprotonation via a geometrically convenient six-membered
      transition state. Dissociation of the distal OAc arm, however, leads to a higher
      energy four-membered (sigma-bond metathesis) transition state, while oxidative
      addition is even higher in energy. For this Ir3+ system, these three mechanisms
      appear to lie within a continuum in which the participation of the metal center
      and an H-accepting ancillary ligand are inversely related. The ability of the
      ancillary ligand to act as a proton acceptor is the key factor in determining
      which mechanism pertains.

PMID- 16568980
TI  - Rational modulation of the periodicity in linear hydrogen-bonded assemblies of
      trimesic acid on surfaces.
AB  - We demonstrate a surprising cooperative adsorption process at the liquid-solid
      interface, involving self-assembly in which a three-fold hydrogen-bonding unit
      (trimesic acid, TMA) is forced into a linear pattern by noncovalent interaction
      with an alcohol. Our work shows that the unexpected linear pattern formed by
      coadsorption of TMA and alcohols can be modulated in size by choosing alcohols
      with different chain lengths.

PMID- 16568981
TI  - An S = 6 cyanide-bridged octanuclear FeIII4NiII4 complex that exhibits slow
      relaxation of the magnetization.
AB  - The synthesis and structural and magnetic characterization of an S = 6 cyanide
      bridged octanuclear FeIII4NiII4 (1) complex is described. Ac susceptibility and
      mu-SQUID measurements suggest that fast magnetization relaxation is present in
      zero-field due to quantum tunneling of the ground spin state (QTM) while
      application of small magnetic fields induces slow relaxation of the
      magnetization.

PMID- 16568982
TI  - Rational design and HT techniques allow the synthesis of new IWR zeolite
      polymorphs.
AB  - By combining a rational design of structure directing agents and high throughput
      and data mining techniques, it has been possible to obtain Ge-free ITQ-24 as pure
      silica as well as borosilicate polymorphs up to a Si/TIII ratio of 10. Al can be
      exchanged by B giving strong acid materials. Also, the availability of the pure
      silica material allows one to determine more precisely the crystal symmetry. This
      work opens the possibility to synthesize the Ge-free polymorphs of a large number
      of new germanosilicate structures reported in the last five years. This certainly
      will increase their possibilities for industrial application.

PMID- 16568983
TI  - 2D supramolecular structures of a shape-persistent macrocycle and co-deposition
      with fullerene on HOPG.
AB  - Two 2D supramolecular structures of macrocycle 1 and 1/C60 have been obtained on
      HOPG by self-assembly under ambient conditions and investigated by high
      resolution STM. The monolayers of 1 are characterized by structures with perfect
      ordering over relatively large areas. In the case of 1/C60, the size of the
      macrocycle 1 and the presence of two individual bithiophene units per ring lead
      in the final superstructure to a 1:2 stoichiometry. The fullerenes are not
      trapped at the graphite surface inside the macrocyclic holes but are located
      around the periphery of the bithiophene units. This clearly shows that the donor
      acceptor interaction between C60 and the electron-rich units of the ring is the
      dominant factor for the structure formation.

PMID- 16568984
TI  - Photochemical stitching of a tubularly assembled hexabenzocoronene amphiphile by
      dimerization of coumarin pendants.
AB  - A coumarin-appended amphiphilic hexa-peri-hexabenzocoronene (1) self-assembled to
      form graphitic nanotubes. Upon irradiation of lambda > 300 nm, the nanotubes in
      the solid state and suspension both underwent dimerization of the coumarin
      pendants, affording covalently stitched nanotubes, which were hardly soluble in
      CHCl3, a good solvent of 1. In contrast, a thin film cast from a homogeneous
      solution of 1 was intact to photoirradiation. Owing to the reversible nature of
      the photochemical stitching, both negative and positive patterns of the graphitic
      nanotubes were developed on a silicon substrate by a lithographic post
      processing.

PMID- 16568985
TI  - Immobilization of sodium ions on the pore surface of a porous coordination
      polymer.
AB  - A porous coordination polymer (PCP) with immobilization of sodium cations on the
      pore surface has been synthesized, by employing a bifunctional
      carboxylate/sulfonate ligand, and structurally characterized. The porous
      framework with 1D channels of the dimension of 4.9 x 4.9 A2 shows high thermal
      stability ( approximately 330 degrees C), affording Type I adsorption isotherms
      for CO2, acetone, and benzene. The chemical shift of 13C NMR and characteristic
      adsorption energy (betaE0) of acetone adsorbed in this compound represent the
      Lewis acidity of this framework.

PMID- 16568986
TI  - Critical properties of aluminum.
AB  - Gibbs ensemble Monte Carlo calculations are performed using a validated embedded
      atom potential to obtain the vapor-liquid coexistence curve for elemental
      aluminum in good agreement with available experimental data up to the boiling
      point. These calculations are then extended to make a reliable prediction of the
      critical temperature, pressure, and density of Al, which have previously been
      known only with very large uncertainties. This demonstrates the ability of modern
      simulations to predict fundamental physical properties that are extremely
      difficult to measure directly.

PMID- 16568987
TI  - An improved class of sugar-binding boronic acids, soluble and capable of
      complexing glycosides in neutral water.
AB  - This study describes a new class of carbohydrate-binding boronic acids. ortho
      Hydroxymethyl phenylboronic acid (boronophthalide) was shown to be superior to
      the well-established dialkylamino ("Wulff-type") analogues, and it is more
      soluble in aqueous solvents. The most significant finding in this work is the
      surprising ability of ortho-hydroxyalkyl arylboronic acids to complex model
      glycopyranosides under physiologically relevant conditions. These boronic acid
      units appear to complex hexopyranosides mainly using their 4,6-diol. This
      behavior is significant because a majority of cell-surface glycoconjugates
      present free 4,6-diols. Thus, conjugatable forms of these boronic acids could be
      used in the design of oligomeric receptors and sensors to exploit multivalency
      effects. Such receptors could dramatically expand the potential of boronic acids
      toward the selective recognition of cell-surface glycoconjugates.

PMID- 16568988
TI  - Synthesis, structure, and bonding of stable dialkylsilaketenimines.
AB  - Stable (N-aryl)- and (N-alkyl)dialkylsilaketenimines R2SiCNR' [R = 1,1,4,4
      tetrakis(trimethylsilyl)butane-1,4-diyl, R' = 2,6-diisopropylphenyl (2a) and 1
      adamantyl (2b)] were synthesized as blue and red crystals by the reactions of
      isolable dialkylsilylene 3 with 2,6-diisopropylphenyl isocyanide and 1-adamantyl
      isocyanide. X-ray single-crystal analysis disclosed that molecular structures of
      2a and 2b were close to each other and were characterized to be allenic rather
      than zwitterionic or a silylene-isocyanide complex. The bonding characteristics
      of silaketenimines are found to be affected strongly by the substituents on
      silicon and nitrogen atoms. Remarkable red-shift of the pi(Si=C) --> pi*(C=N)
      band of 2a [lambdamax/nm (epsilon) 647(156)] compared with that of 2b [465 nm
      (109)] is ascribed to lowering of the pi*(C=N) orbital level due to significant
      interaction between pi*(C=N) and pi*(N-aryl) orbitals.

PMID- 16568989
TI  - Kinetic resolution of protected alpha-amino acid derivatives by a chiral O
      nucleophilic acyl transfer catalyst.
AB  - The kinetic resolution of alpha-trifluoroacetamido N-acyl oxazolidinethiones
      using 5-10% of the chiral, nonracemic O-nucleophilic acyl transfer catalyst 2 is
      described. A variety of substrates participate in this reaction in excellent
      yields, with s-factors ranging from 20 to 86.

PMID- 16568990
TI  - Asymmetric claisen rearrangements enabled by catalytic asymmetric Di(allyl) ether
      synthesis.
AB  - Merging the catalytic asymmetric synthesis of di(allyl) ethers with ensuing
      olefin isomerization-Claisen rearrangement (ICR) reactions provides a convenient,
      two-step route to asymmetric aliphatic Claisen rearrangements from easily
      obtained starting materials. These reactions deliver the 2,3-disubstituted 4
      pentenal derivatives characteristic of aliphatic Claisen rearrangements with
      excellent relative and absolute stereocontrol. A catalytic enantioselective
      synthesis of the (+)-calopin dimethyl ether demonstrates the utility of this
      reaction technology in asymmetric synthesis enterprises.

PMID- 16568992
TI  - Corking nano test tubes by chemical self-assembly.
AB  - There is tremendous current interest in using nanoparticles to deliver
      biomolecules and macromolecules (e.g., drugs and DNA) to specific sites in living
      systems. Release of the biomedical payload from the nanoparticle can be
      accomplished by chemical or enzymatic degradation of the nanoparticle or of the
      link between the payload and the nanoparticle. We are exploring an alternative
      payload-release strategy that builds on our work on template-synthesized nano
      test tubes. These are hollow nanotubes that are closed on one end and open on the
      other, and the dimensions can be controlled at will. If these nano test tubes
      could be filled with a payload and then the open end corked with a chemically
      labile cap, they might function as a universal delivery vehicle. We show here
      that silica nano test tubes can be covalently corked by chemical self-assembly of
      nanoparticles to the tubes. We also show that the nanoparticle corks remain
      attached to the mouths of the nano test tubes after liberation from the alumina
      template. For this proof-of-principle study, we used simple imine linkages to
      attach the corks to the test tubes. Schiff's bases are thermodynamically unstable
      in the presence of water; however, the multiple points of contact between the
      nano test tubes and nanoparticles allow the assembled structure to be metastable
      under our experimental conditions. Other chemical linkages-either more or less
      stable-may be more appropriate for other applications, and these are currently
      under development.

PMID- 16568993
TI  - An efficient route to well-defined macrocyclic polymers via "click" cyclization.
AB  - Polystyrene macrocycles have been prepared from ATRP precursors by modification
      of the terminal bromide to an azide, followed by "click" cyclization with a
      pendant alkyne from the initiator. This route offers exceptional control over the
      size and polydispersity of the macrocyclic polymers, as well as providing
      tolerance to a number of functional groups.

PMID- 16568991
TI  - An O-GlcNAcase-specific inhibitor and substrate engineered by the extension of
      the N-acetyl moiety.
AB  - A novel analogue of PUGNAc, a potent O-GlcNAcase inhibitor, was synthesized and
      analyzed as an inhibitor of O-GlcNAcase, hexosaminidase A, and hexosaminidase B.
      While PUGNAc does not demonstrate selective inhibition of these related enzymes,
      the extension of the acetyl moiety to the longer butyl chain provided a compound
      with depressed inhibition of O-GlcNAcase and no observed inhibition of either
      hexosaminidase A or hexosaminidase B. Further, we applied this knowledge of
      substrate recognition at the N-acetyl group to our recently reported fluorogenic
      substrate for monitoring O-GlcNAcase activity. Gratifyingly, this altered small
      molecule was demonstrated to be a potent substrate for O-GlcNAcase while
      possessing no activity at hexosaminidase A. This reagent provides, for the first
      time, a means for monitoring O-GlcNAcase activity independent of the related
      enzymes hexosaminidase A and hexosaminidase B.

PMID- 16568994
TI  - Radical phosphination of organic halides and alkyl imidazole-1-carbothioates.
AB  - Taking advantage of a radical-based methodology, mild and chemoselective
      phosphination reactions of organic halide and alkyl imidazole-1-carbothioates
      have been developed. The mild reaction conditions allow labile functional groups
      to survive during the reaction.

PMID- 16568995
TI  - DDQ-mediated direct cross-dehydrogenative-coupling (CDC) between benzyl ethers
      and simple ketones.
AB  - A direct Cross-Dehydrogenative-Coupling (CDC) between benzyl ethers and simple
      ketones was developed without using any metal catalyst. By using DDQ, various
      benzyl ethers and simples ketones were coupled together directly to form beta
      alkoxyl ketones efficiently. A mechanism in which the DDQ serves the double roles
      of an oxidizing agent and an organomediator was proposed.

PMID- 16568997
TI  - Room temperature palladium-catalyzed intramolecular hydroamination of unactivated
      alkenes.
AB  - A mild and facile Pd-catalyzed intramolecular hydroamination of unactivated
      alkenes is described. This reaction takes place at room temperature and is
      tolerant of synthetically useful acid-sensitive functional groups. The formation
      of hydroamination products rather than oxidative amination products is due to the
      use of a tridentate ligand on Pd which effectively inhibits beta-hydride
      elimination.

PMID- 16568996
TI  - Tight binding inhibitors of N-acyl amino sugar and N-acyl amino acid
      deacetylases.
AB  - Very potent inhibitors were synthesized for the enzymatic deacetylation of N
      acetyl-d-glucosamine-6-phosphate (NagA) and N-acetyl-d-glutamate (DGD). The
      methyl phosphonamidate derivative of d-glucosamine-6-phosphate bound to N-acetyl
      d-glucosamine-6-phosphate deacetylase with an equilibrium dissociation constant
      of 34 +/- 5 nM at pH 7.5 and an association rate constant of 6.1 x 103 M-1 s-1.
      The inhibition constant is 4000-fold lower than the Michaelis constant for the
      substrate N-acetyl-d-glucosamine-6-phosphate. N-Acetyl-d-glutamate deacetylase
      was inhibited by the methyl phosphonamidate derivative of d-glutamate with an
      inhibition constant of 460 +/- 70 pM at pH 7.6. The inhibitor bound to the enzyme
      500 000-fold tighter than the Michaelis constant for N-formyl-d-glutamate. These
      compounds mimic the putative tetrahedral intermediate formed upon nucleophilic
      attack of an activated water molecule on the amide bond of the target substrate.
      These inhibitors should prove useful in the elucidation of the enzyme-substrate
      interactions for enzymes within the amidohydrolase superfamily.

PMID- 16568998
TI  - Reducing power of three-coordinate cobalt(I).
AB  - Carbon monoxide adds easily to (PNP)Co, PNP = N(SiMe2CH2PtBu2)2, to give
      (PNP)Co(CO), whose nuco value of 1885 cm-1 suggests much back-donation, and thus
      an easily oxidized Co(I) in (PNP)Co. However, Co(III) is inaccessible from
      (PNP)Co by oxidation with I2, the products being first (PNP)CoI, then the
      zwitterion [ItBu2PCH2SiMe2NSiMe2CH2PtBu2]CoI2. The potential two-electron oxidant
      N2CH(SiMe3) reacts with (PNP)Co to form a 1:1 "adduct", whose crystal structure
      is most consistent with oxidation of Co(I), but not fully to Co(III).

PMID- 16568999
TI  - Reflective interferometric fourier transform spectroscopy: a self-compensating
      label-free immunosensor using double-layers of porous SiO2.
AB  - An interferometric biosensor comprised of two layers of porous Si, stacked one on
      top of the other, is described. A fast Fourier transform (FFT) of the
      reflectivity spectrum reveals three peaks that correspond to the optical
      thickness of the top layer, the bottom layer, and both layers together. Binding
      of immunoglobulin G to a protein A capture probe adsorbed to the surface of the
      top layer induces changes in reflectivity at the top layer/solution interface.
      The FFT method allows discrimination of target analyte binding from matrix
      effects due to nonspecific changes in the analyte solution. The sensor response
      is shown to be insensitive to the addition of 4000-fold excess sucrose or 80-fold
      excess bovine serum albumin interferents.

PMID- 16569000
TI  - Ultrafast charge separation in a photoreactive rhenium-appended porphyrin
      assembly monitored by picosecond transient infrared spectroscopy.
AB  - Rhenium(bipyridine)(tricarbonyl)(picoline) units have been linked covalently to
      tetraphenylmetalloporphyrins of magnesium and zinc via an amide bond between the
      bipyridine and one phenyl substituent of the porphyrin. The resulting complexes,
      abbreviated as [Re(CO)(3)(Pic)Bpy-MgTPP][OTf] and [Re(CO)(3)(Pic)Bpy-ZnTPP][OTf],
      exhibit no signs of electronic interaction between the Re(CO)(3)(bpy) units and
      the metalloporphyrin units in their ground states. However, emission spectroscopy
      reveals solvent-dependent quenching of porphyrin emission on irradiation into the
      long-wavelength absorption bands localized on the porphyrin. The characteristics
      of the excited states have been probed by picosecond time-resolved absorption
      (TRVIS) spectroscopy and time-resolved infrared (TRIR) spectroscopy in nitrile
      solvents. The presence of the charge-separated state involving electron transfer
      from MgTPP or ZnTPP to Re(bpy) is signaled in the TRIR spectra by a low-frequency
      shift in the nu(CO) bands of the Re(CO)(3) moiety similar to that observed by
      spectroelectrochemical reduction. Long-wavelength excitation of
      [Re(CO)(3)(Pic)Bpy-MTPP][OTf] results in characteristic TRVIS spectra of the S(1)
      state of the porphyrin that decay with a time constant of 17 ps (M = Mg) or 24 ps
      (M = Zn). The IR bands of the CS state appear on a time scale of less than 1 ps
      (Mg) or ca. 5 ps (Zn) and decay giving way to a vibrationally excited (i.e., hot)
      ground state via back electron transfer. The IR bands of the precursors recover
      with a time constant of 35 ps (Mg) or 55 ps (Zn). The short lifetimes of the
      charge-transfer states carry implications for the mechanism of reaction in the
      presence of triethylamine.

PMID- 16569002
TI  - J-aggregation in alpha-sexithiophene submonolayer films on silicon dioxide.
AB  - We report on the observation of J-aggregates in submonolayer films of alpha
      sexithiophene grown on silicon dioxide. Photoluminescence spectroscopy reveals
      that submonolayers are formed by molecules lying flat on the substrate with a
      head to tail configuration. Excitation energy dependence of photoluminescence
      shows a red-shifted absorption with respect to isolated molecules and a
      negligible Stokes shift between absorption and emission. The pronounced
      structural order of J-aggregates is reflected in the fwhm of the emission bands.
      From time-resolved and low-temperature photoluminescence experiments, we infer a
      quantum yield of the J-aggregate between 0.6 and 1. The demonstration of
      spontaneous formation of J-aggregates of pi-conjugated systems on amorphous
      silicon-based substrates can be relevant for the development of organic-inorganic
      hybrid photonic devices.

PMID- 16569001
TI  - 8-Bromo-7-hydroxyquinoline as a photoremovable protecting group for physiological
      use: mechanism and scope.
AB  - Two-photon excitation (2PE) of "caged" biomolecules represents a powerful method
      to investigate the temporal and spatial relevance of physiological function in
      real time and on living tissue, because the excitation volume can be restricted
      to 1 fL. Additionally, low-energy IR light is used, which minimizes tissue
      destruction and enables deeper penetration into tissue preparations. Exploitation
      of this technology for studying cell physiology requires the further development
      of photoremovable protecting groups with sufficient sensitivity to 2PE for use in
      "caged" compounds. 8-Bromo-7-hydroxyquinoline (BHQ) is efficiently photolyzed by
      classic 1PE (365 nm) and 2PE (740 nm) under simulated physiological conditions
      (aqueous buffer of high ionic strength, pH 7.2) to release carboxylates,
      phosphates, and diols-functional groups commonly found on bioactive molecules
      such as neurotransmitters, nucleic acids, and drugs. It is stable in the dark,
      soluble in water, and exhibits low levels of fluorescence, which will enable use
      in conjunction with fluorescent indicators of biological function. BHQ-protected
      effectors are synthetically accessible. Stern-Volmer quenching, time-resolved
      infrared (TRIR), and (18)O-labeling experiments suggest that the photolysis
      occurs through a solvent-assisted photoheterolysis (S(N)1) reaction mechanism on
      the sub-microsecond time scale. BHQ has the requisite photochemical and
      photophysical properties as a photoremovable protecting group to regulate the
      action of biological effectors in cell and tissue culture with light, especially
      2PE.

PMID- 16569003
TI  - Probing the intrinsic electronic structure of the bis(dithiolene) anions
      [M(mnt)2]2- and [M(mnt)2]1- (M = Ni, Pd, Pt; mnt = 1,2-S2C2(CN)2) in the gas
      phase by photoelectron spectroscopy.
AB  - A detailed understanding of the electronic structure of transition metal
      bis(dithiolene) complexes is important because of their interesting redox,
      magnetic, optical, and conducting properties and their relevance to enzymes
      containing molybdenum and tungsten bis(dithiolene) centers. The electronic
      structures of the bis(dithiolene) anions [M(mnt)(2)](n-) (M = Ni, Pd, Pt; mnt =
      1,2-S(2)C(2)(CN)(2); n = 0-2) were examined by a combination of photodetachment
      photoelectron spectroscopy (PES) and density functional theory calculations. The
      combined experimental and theoretical data provide insight into the molecular
      orbital energy levels of [M(mnt)(2)](2-) and the ground and excited states of
      [M(mnt)(2)](1-) and [M(mnt)(2)]. Detachment features from ligand-based orbitals
      of [M(mnt)(2)](2-) occur at similar energies for each species, independent of the
      metal center, while those arising from metal-based orbitals occur at higher
      energies for the heavier congeners. Electronic excitation energies inferred for
      [M(mnt)(2)](1-) from the PES experiments agree well with those obtained in
      optical absorption experiments in solution, with the PES experiments providing
      additional insight into the changes in energy of these transitions as a function
      of metal. The singly charged anions [M(mnt)(2)](1-) were also prepared and
      studied independently. Electron detachment from the ground states of these
      doublet anions accessed the lowest singlet and triplet states of neutral
      [M(mnt)(2)], thereby providing a direct experimental measure of their singlet
      triplet splitting.

PMID- 16569004
TI  - CP/MAS 13C NMR characterization of the isomeric states and intermolecular packing
      in tris(8-hydroxyquinoline) aluminum(III) (Alq3).
AB  - The isomeric states and intermolecular packing of tris(8-hydroxyquinoline)
      aluminum(III) (Alq(3)) in the alpha-, gamma-, and delta-crystalline forms and in
      the amorphous state, which are important for understanding the light-emitting and
      electron-transport properties, have been analyzed by CP/MAS (13)C NMR. This
      simple NMR experiment shows that the isomeric state of alpha- and amorphous
      Alq(3) is meridional, whereas that of gamma- and delta-Alq(3) is facial. In the
      amorphous Alq(3), the inclusion of facial isomers has been under debate. Our
      experiments show that meridional isomers are dominant in the amorphous Alq(3),
      although the existence of facial isomers cannot be completely denied. The local
      structure of amorphous Alq(3) is similar to that of alpha-Alq(3) and is
      significantly different from those of gamma- and delta-Alq(3). Among these Alq(3)
      samples, the effect of intermolecular interaction is not found only for gamma
      Alq(3). This finding can explain the good solvent solubility of gamma-Alq(3),
      compared with the other crystalline forms. It is also shown that the structures
      are locally disordered not only for amorphous Alq(3) but also for alpha-Alq(3),
      although clear X-ray diffraction peaks are observed for alpha-Alq(3). In
      contrast, the local structures of gamma- and delta-Alq(3) are well defined. A
      clear relation is found between the spectral patterns of CP/MAS (13)C NMR and the
      fluorescence wavelengths; the samples, which consist of facial isomers, show blue
      shifted fluorescence compared with those of meridionals.

PMID- 16569005
TI  - Tandem chain walking polymerization and atom transfer radical polymerization for
      efficient synthesis of dendritic nanoparticles for bioconjugation.
AB  - A tandem polymerization methodology, chain walking polymerization (CWP) followed
      by atom transfer radical polymerization, was developed for efficient synthesis of
      nanoparticles for bioconjugation. Using the chain walking palladium-alpha-diimine
      catalyst (catalyst 1), dendritic polymers bearing multiple initiation sites were
      synthesized and used as macroinitiators for subsequent Cu(I)-mediated ATRP.
      Control of molecular weight and size of the water-soluble core-shell polymeric
      nanoparticles was achieved by tuning reaction conditions. Addition of an N
      acryloyloxysuccinamide (NAS) monomer at the end of the ATRP afforded NHS
      activated polymer nanoparticles. Conjugation with both small dye molecules and
      protein (ovalbumin) yielded nanoparticle conjugates with relatively high dye or
      protein per particle ratio. With the efficient synthesis and good
      biocompatibility, these nanoparticles may find many potential applications in
      bioconjugation.

PMID- 16569007
TI  - Monitoring temporal evolution of silicate species during hydrolysis and
      condensation of silicates using mass spectrometry.
AB  - The first stages of solid-state formation from solution can be crucial in
      determining the properties of the resulting solids. We are trying to approach
      prenucleation reactions of silicates from an aqueous solution containing
      tetraalkylammoniumhydroxides (TAAOH) and tetraalkoxysilanes (TAOS) by analyzing
      hydrolysis and condensation using electrospray mass spectrometry (ESI MS). Time
      resolved measurements were performed using different reactor systems to show the
      stepwise hydrolysis of the silanes and subsequent condensation of silicate
      monomers via oligomers to form larger units. We approached the precipitation
      point by varying the pH and the concentrations of the reactants. The results show
      the evolution of different silicate species occurring during condensation. No
      defined molecular entities were identified at pH values close to precipitation,
      which suggests that under the conditions used, solids are probably not formed
      from defined building blocks.

PMID- 16569008
TI  - Nature of the bottom t2g-block bands of layered perovskites. Implications for the
      transport properties of phases where these bands are partially filled.
AB  - The electronic structure of a series of double layer (Sr(3)V(2)O(7),
      KLaNb(2)O(7), Li(2)SrNb(2)O(7), RbLaNb(2)O(7), Rb(2)LaNb(2)O(7)) as well as
      triple layer (Ca(4)Ti(3)O(10), K(2)La(2)Ti(3)O(10), Sr(4)V(3)O(9.7),
      CsCa(2)Nb(3)O(10)) Dion-Jacobson and Ruddlesden-Popper phases and quadruple layer
      A(n)()B(n)(O(3)(n)(+2) phases (Sr(2)Nb(2)O(7) as well as the low-temperature and
      room-temperature structures of Sr(2)Ta(2)O(7)) has been studied by means of a
      first-principles density functional theory approach. The results are rationalized
      on the basis of a simple tight-binding scheme, which provides a simple yet
      precise scheme allowing the correlation of the crystal structure details and the
      nature of the bottom t(2g)-block band levels. Both the quantitative and the
      qualitative approaches are used to analyze the nature of the carriers in
      intercalated samples of the d(0) semiconducting phases as well as those of the
      metallic d(x) (0 < x < or = 1) systems. The Ruddlesden-Popper and Dion-Jacobson
      materials with partially filled t(2g)-block bands must be genuine two-dimensional
      metals except when the M-O(ap) distances of the outer layer octahedra are similar
      and the band filling is not low. The conducting electrons in these phases are
      almost equally distributed among the different layers. It is shown that the
      A(n)()B(n)O(3)(n)(+2) phases with partially filled bands are potentially
      interesting materials because they are structurally two-dimensional materials
      exhibiting one-dimensional band structure features. Finally, the possible
      application of the simple scheme to related materials such as layered perovskite
      oxynitrides and the effect of disorder are briefly discussed.

PMID- 16569006
TI  - Spiropyran-based photochromic polymer nanoparticles with optically switchable
      luminescence.
AB  - Polymer nanoparticles of 40-400 nm diameter with spiropyran-merocyanine dyes
      incorporated into their hydrophobic cavities have been prepared; in contrast to
      their virtually nonfluorescent character in most environments, the merocyanine
      forms of the encapsulated dyes are highly fluorescent. Spiro-mero
      photoisomerization is reversible, allowing the fluorescence to be switched "on"
      and "off" by alternating UV and visible light. Immobilizing the dye inside
      hydrophobic pockets of nanoparticles also improves its photostability, rendering
      it more resistant than the same dyes in solution to fatigue effects arising from
      photochemical switching. The photophysical characteristics of the encapsulated
      fluorophores differ dramatically from those of the same species in solution,
      making nanoparticle-protected hydrophobic fluorophores attractive materials for
      potential applications such as optical data storage and switching and biological
      fluorescent labeling. To evaluate the potential for biological tagging, these
      optically addressable nanoparticles have been delivered into living cells and
      imaged with a liquid nitrogen-cooled CCD.

PMID- 16569010
TI  - Interplay of stereoelectronic and enviromental effects in tuning the structural
      and magnetic properties of a prototypical spin probe: further insights from a
      first principle dynamical approach.
AB  - The nitrogen isotropic hyperfine coupling constant (hcc) and the g tensor of a
      prototypical spin probe (di-tert-butyl nitroxide, DTBN) in aqueous solution have
      been investigated by means of an integrated computational approach including Car
      Parrinello molecular dynamics and quantum mechanical calculations involving a
      discrete-continuum embedding. The quantitative agreement between computed and
      experimental parameters fully validates our integrated approach. Decoupling of
      the structural, dynamical, and environmental contributions acting onto the
      spectral observables allows an unbiased judgment of the role played by different
      effects in determining the overall experimental observables and highlights the
      importance of finite-temperature vibrational averaging. Together with their
      intrinsic interest, our results pave the route toward more reliable
      interpretations of EPR parameters of complex systems of biological and
      technological relevance.

PMID- 16569009
TI  - NO reductase activity of the tetraheme cytochrome C554 of Nitrosomonas europaea.
AB  - The tetraheme cytochrome c(554) (cyt c(554)) from Nitrosomonas europaea is
      believed to function as an electron-transfer protein from hydroxylamine
      oxidoreductase (HAO). We show here that cyt c(554) also has significant NO
      reductase activity. The protein contains one high-spin and three low-spin c-type
      hemes. HAO catalyzed reduction of the cyt c(554), ligand binding, intermolecular
      electron transfer, and kinetics of NO reduction by cyt c(554) have been
      investigated. We detect the formation of a NO-bound ferrous heme species in cyt
      c(554) by EPR and Mossbauer spectroscopies during the HAO catalyzed oxidation of
      hydroxylamine, indicating that N-oxide intermediates produced from HAO readily
      bind to cyt c(554). In the half-reduced state of cyt c(554), we detect a spin
      interaction between the [FeNO](7) state of heme 2 and the low-spin ferric state
      of heme 4. We find that ferrous cyt c(554) will reduce NO at a rate greater than
      16 s(-1), which is comparable to rates of other known NO reductases. Carbon
      monoxide or nitrite are shown not to bind to the reduced protein, and previous
      results indicate the reactions with O(2) are slow and that a variety of ligands
      will not bind in the oxidized state. Thus, the enzymatic site is highly selective
      for NO. The NO reductase activity of cyt c(554) may be important during ammonia
      oxidation in N. europaea at low oxygen concentrations to detoxify NO produced by
      reduction of nitrite or incomplete oxidation of hydroxylamine.

PMID- 16569011
TI  - Mechanism of Pd(OAc)2/DMSO-catalyzed aerobic alcohol oxidation: mass-transfer
      limitation effects and catalyst decomposition pathways.
AB  - Pd(OAc)(2) in DMSO is an effective catalyst for the aerobic oxidation of alcohols
      and numerous other organic substrates. Kinetic studies of the catalytic oxidation
      of primary and secondary benzylic alcohol substrates provide fundamental insights
      into the catalytic mechanism. In contrast to the conclusion reached in our
      earlier study (J. Am. Chem. Soc. 2002, 124, 766-767), we find that Pd(II)
      mediated alcohol oxidation is the turnover-limiting step of the catalytic
      reaction. At elevated catalyst loading, however, the rate of catalytic turnover
      is limited by the dissolution of oxygen gas into solution. This mass-transfer
      rate is measured directly by using gas-uptake methods, and it correlates with the
      maximum rate observed during catalysis. Initial-rate studies were complemented by
      kinetic analysis of the full-reaction timecourses at different catalyst
      concentrations. Kinetic fits of these traces reveal the presence of unimolecular
      and bimolecular catalyst decomposition pathways that compete with productive
      catalytic turnover.

PMID- 16569012
TI  - Electron donor-bridge-acceptor molecules with bridging nitronyl nitroxide
      radicals: influence of a third spin on charge- and spin-transfer dynamics.
AB  - Appending a stable radical to the bridge molecule in a donor-bridge-acceptor
      system (D-B-A) is potentially an important way to control charge- and spin
      transfer dynamics through D-B-A. We have attached a nitronyl nitroxide (NN*)
      stable radical to a D-B-A system having well-defined distances between the
      components: MeOAn-6ANI-Ph(NN*)-NI, where MeOAn = p-methoxyaniline, 6ANI = 4-(N
      piperidinyl)naphthalene-1,8-dicarboximide, Ph = phenyl, and NI = naphthalene
      1,8:4,5-bis(dicarboximide). MeOAn-6ANI, NN*, and NI are attached to the 1, 3, and
      5 positions of the Ph bridge. Using both time-resolved optical and EPR
      spectroscopy, we show that NN* influences the spin dynamics of the photogenerated
      triradical states (2,4)(MeOAn(+)*-6ANI-Ph(NN*)-NI(-)*), resulting in slower
      charge recombination within the triradical compared to the corresponding
      biradical lacking NN*. The observed spin-spin exchange interaction between the
      photogenerated radicals MeOAn(+)(*) and NI(-)(*) is not altered by the presence
      of NN*, which only accelerates radical pair intersystem crossing. Charge
      recombination within the triradical results in the formation of (2,4)(MeOAn-6ANI
      Ph(NN*)-(3)NI), in which NN* is strongly spin-polarized. Normally, the spin
      dynamics of correlated radical pairs do not produce a net spin polarization;
      however, net spin polarization appears on NN* with the same time constant as
      describes the photogenerated radical ion pair decay. This effect is attributed to
      antiferromagnetic coupling between NN* and the local triplet state (3)NI, which
      is populated following charge recombination. This requires an effective switch in
      the spin basis set between the triradical and the three-spin charge recombination
      product having both NN* and (3)NI present.

PMID- 16569013
TI  - Excited-state dynamics of structurally characterized [ReI(CO)3(phen)(HisX)]+ (X =
      83, 109) Pseudomonas aeruginosa azurins in aqueous solution.
AB  - The triplet metal-to-ligand charge transfer ((3)MLCT) dynamics of two
      structurally characterized Re(I)(CO)(3)(phen)(HisX)-modified (phen = 1,10
      phenanthroline; X = 83, 109) Pseudomonas aeruginosa azurins have been
      investigated by picosecond time-resolved infrared (TRIR) spectroscopy in aqueous
      (D(2)O) solution. The (3)MLCT relaxation dynamics exhibited by the two Re(I)
      azurins are very different from those of the sensitizer
      [Re(I)(CO)(3)(phen)(im)](+) (im = imidazole). Whereas the Re(I)(CO)(3)
      intramolecular vibrational relaxation in Re(I)(CO)(3)(phen)(HisX)Az (4 ps) is
      similar to that of [Re(I)(CO)(3)(phen)(im)](+) (2 ps), the medium relaxation is
      much slower ( approximately 250 vs 9.5 ps); the 250-ps relaxation is attributable
      to reorientation of D(2)O molecules as well as structural reorganization of the
      rhenium chromophore and nearby polar amino acids in each of the modified
      proteins.

PMID- 16569014
TI  - Conformational fluctuations affect protein alignment in dilute liquid crystal
      media.
AB  - The discovery of dilute liquid crystalline media to align biological
      macromolecules has opened many new possibilities to study protein and nucleic
      acid structures by NMR spectroscopy. We inspect the basic alignment phenomenon
      for an ensemble of protein conformations to deduce relative contributions of each
      member to the residual dipolar coupling signals. We find that molecular
      fluctuations can affect the alignment and discover a resulting emphasis of
      certain conformations. However, the internal fluctuations are largely
      uncorrelated with those of the alignment, implying that proteins have liquidlike
      molecular surfaces. Furthermore, we consider the implications of a dynamic bias
      to structure determination using data from the weak alignment method.

PMID- 16569015
TI  - Stereoretentive elimination and trans-olefination of the dicationic dipalladium
      moiety [Pd2Ln]2+ bound on 1,3,5-trienes.
AB  - The reaction of [Pd(2)(CH(3)CN)(6)][BF(4)](2) (1) with 1,3,5-hexatriene, 1,6
      diphenyl-1,3,5-hexatriene (DPHT), or 2,2,9,9-tetramethyl-3,5,7-decatriene (DBHT)
      afforded bi-eta(3)-allyldipalladium complexes 3, 4, or 5. The reaction of 1 and
      DBHT proceeded in a stereospecific (syn) manner when the reaction was carried out
      in CD(2)Cl(2) under aerobic conditions, while a mixture of two diastereomers was
      formed under N(2) atmosphere. The two diastereomers (5-E,Z,E-antifacial and 5
      E,E,E-antifacial) formed from DBHT were isolated, and the structure of 5-E,Z,E
      antifacial, which was kinetically formed from the reaction of 1 and (E,E,E)-DBHT,
      was determined by X-ray diffraction analysis. Addition of phosphine ligands
      (PPh(3) or dppm) to the dinuclear adduct 5-E,Z,E-antifacial or 5-E,E,E-antifacial
      in acetonitrile resulted in the stereospecific (syn) elimination of
      [Pd(2)(PPh(3))(2)(CH(3)CN)(4)][BF(4)](2) (2) or
      [Pd(2)(dppm)(2)(CH(3)CN)(2)][BF(4)](2) (6). During the PPh(3)-induced dinuclear
      elimination, the phosphine adducts 7 that retain bi-eta(3)-allyldipalladium
      structure were observed initially. The phosphine adduct generated from 5-E,E,E
      antifacial was isolated and structurally characterized by X-ray diffraction
      analysis. The reaction of 1 and DPHT in CH(2)Cl(2) afforded unique dipalladium
      sandwich compounds [Pd(2)(mu-eta(3):eta(3)-DPHT)(2)][BF(4)](2) (8).
      Interconversion between the sandwich complexes and half-sandwich complexes
      occurred in a stereoretentive manner. The structure of the sandwich complex 8
      E,Z,E formed from 4-E,E,E-antifacial and (E,Z,E)-DPHT was determined by X-ray
      diffraction analysis. Transfer of the dipalladium moiety [Pd(2)(CH(3)CN)(4)](2+)
      from DPHT ligand of 4-E,E,E-antifacial onto DBHT ligand proceeded in a
      stereoretentive manner. The observed stereoretentive dinuclear process is
      featured by the pairwise behavior of two palladium atoms sitting on the triene pi
      plane. In the dinuclear elimination, the two Pd atoms that are initially in the
      divalent state and bound on the opposite faces (antifacial) come to the synfacial
      positions to form a Pd-Pd bond prior to dissociation. These results represent the
      unique property of conjugated olefin as the multidentate ligands for metal-metal
      moieties.

PMID- 16569018
TI  - Hyperbaric laser chemical vapor deposition of carbon fibers from the 1-alkenes, 1
      alkynes, and benzene.
AB  - The growth of long carbon fibers was investigated using hyperbaric-pressure laser
      chemical vapor deposition (HP-LCVD). Precursors included the unbranched alkenes
      with linear structure 1-C(x)H(2x) (where x = 2,4,5,6,7,8), the unbranched
      alkynes, i.e., 1-C(x)H(2)(x-2) (where x = 3,4,5,6,8), and benzene. Rate
      constants, reaction orders, and apparent activation energies were derived for
      each precursor over a range of experimental conditions. Axial growth rates from
      the alkenes were 1-2 orders of magnitude greater than for the alkynes, while
      growth rates for benzene exceeded 10 mm s(-1). Generalized expressions for the
      growth rate vs molecular weight were determined. For the alkenes, the growth rate
      was directly proportional to the square root of the precursor molecular weight,
      while the alkynes exhibited an inverse relationship. Two regions of differing
      reaction order were identified for the alkynes; at pressures less than 2.0-2.5
      bar, the average reaction order was 3.07, while above 2.0-2.5 bar, reaction
      orders diverged. Expressions were derived for the fraction of carbon atoms
      deposited per alkyne molecule transported; the deposition efficiency decreased
      with molecular weight for the alkynes, due in part to the Soret effect. In
      contrast, the reaction order for the alkenes was 1.65, and for benzene was 2.25.
      A phase change in the deposit was observed for both the alkenes and alkynes, with
      the exceptions of pentene and pentyne. Complete axial rate equations for the
      alkenes and alkynes were derived, as well as volumetric growth equations for the
      alkynes. It was shown that the volumetric rate increases nonlinearly with laser
      power at sufficiently high pressures.

PMID- 16569016
TI  - Site-directed parallel spin-labeling and paramagnetic relaxation enhancement in
      structure determination of membrane proteins by solution NMR spectroscopy.
AB  - A major challenge for the structure determination of integral membrane proteins
      by solution NMR spectroscopy is the limited number of NOE restraints in these
      systems stemming from extensive deuteration. Paramagnetic relaxation enhancement
      (PRE) by means of nitroxide spin-labels can provide valuable long-range distance
      information but, in practice, has limits in its application to membrane proteins
      because spin-labels are often incompletely reduced in highly apolar environments.
      Using the integral membrane protein OmpA as a model system, we introduce a method
      of parallel spin-labeling with paramagnetic and diamagnetic labels and show that
      distances in the range 15-24 Angstroms can be readily determined. The protein was
      labeled at 11 water-exposed and lipid-covered sites, and 320 PRE distance
      restraints were measured. The addition of these restraints resulted in
      significant improvement of the calculated backbone structure of OmpA. Structures
      of reasonable quality can even be calculated with PRE distance restraints only,
      i.e., in the absence of NOE distance restraints.

PMID- 16569019
TI  - A study of DNA tube formation mechanisms using 4-, 8-, and 12-helix DNA
      nanostructures.
AB  - This paper describes the design and characterization of a new family of
      rectangular-shaped DNA nanostructures (DNA tiles) containing 4, 8, and 12
      helices. The self-assembled morphologies of the three tiles were also
      investigated. The motivation for designing this set of DNA nanostructures
      originated from the desire to produce DNA lattices containing periodic cavities
      of programmable dimensions and to investigate the mechanism of DNA tube
      formation. Nine assembly scenarios have been investigated through the combination
      of the three different tiles and three sticky end association strategies. Imaging
      by atomic force microscopy (AFM) revealed self-assembled structures with varied
      cavity sizes, lattice morphologies, and orientations. Six samples show only tube
      formation, two samples show both 2D lattices (>2 microm) and tubes, and one
      sample shows only 2D lattices without tubes. We found that a lower tile
      dimensional anisotropy, weaker connection, and corrugated design favor the large
      2D array formation, while the opposite (higher tile anisotropy, stronger
      connection, and uncorrugated design) favors tube formation. We discuss these
      observations in terms of an energy balance at equilibrium and the kinetic
      competition between diffusion-limited lateral lattice growth versus fluctuation
      of the lattice to form tubes at an early stage of the assembly. The DNA
      nanostructures and their self-assembly demonstrated herein not only provide a new
      repertoire of scaffolds to template the organization of nanoscale materials, but
      may also provide useful information for investigating other self-assembly
      systems.

PMID- 16569017
TI  - Three-dimensional structure of the water-insoluble protein crambin in
      dodecylphosphocholine micelles and its minimal solvent-exposed surface.
AB  - We chose crambin, a hydrophobic and water-insoluble protein originally isolated
      from the seeds of the plant Crambe abyssinica, as a model for NMR investigations
      of membrane-associated proteins. We produced isotopically labeled
      crambin(P22,L25) (variant of crambin containing Pro22 and Leu25) as a cleavable
      fusion with staphylococcal nuclease and refolded the protein by an approach that
      has proved successful for the production of proteins with multiple disulfide
      bonds. We used NMR spectroscopy to determine the three-dimensional structure of
      the protein in two membrane-mimetic environments: in a mixed aqueous-organic
      solvent (75%/25%, acetone/water) and in DPC micelles. With the sample in the
      mixed solvent, it was possible to determine (>NH...OC<) hydrogen bonds directly
      by the detection of (h3)J(NC)' couplings. H-bonds determined in this manner were
      utilized in the refinement of the NMR-derived protein structures. With the
      protein in DPC (dodecylphosphocholine) micelles, we used manganous ion as an
      aqueous paramagnetic probe to determine the surface of crambin that is shielded
      by the detergent. With the exception of the aqueous solvent exposed loop
      containing residues 20 and 21, the protein surface was protected by DPC. This
      suggests that the protein may be similarly embedded in physiological membranes.
      The strategy described here for the expression and structure determination of
      crambin should be applicable to structural and functional studies of membrane
      active toxins and small membrane proteins.

PMID- 16569020
TI  - Vibrational markers for the open-shell character of transition metal bis
      dithiolenes: an infrared, resonance raman, and quantum chemical study.
AB  - Transition metal complexes involving the benzene-1,2-dithiol (L(2-)) and
      Sellmann's 3,5-di-tert-butylbenzene-1,2-dithiol(L(Bu 2-)) ligands have been
      studied by UV-vis, infrared (IR), and resonance Raman (rR) spectroscopies. Raman
      spectra were obtained in resonance with the intervalence charge transfer (IVCT)
      bands in the near-infrared region and ligand-to-metal charge transfer (LMCT)
      bands in the near-UV region. Geometry optimization and frequency calculations
      using density functional theory (DFT) have been performed for [M(L)(2)](z) and
      [M(L(Bu))(2)](z) species (M = Ni, Pd, Pt, Co, Cu, Au, z = -1; M = Au, z = 0). On
      the basis of frequency calculations and normal-mode analysis, we have assigned
      the most important totally symmetric vibrations as well as corresponding overtone
      and combination bands that appear in rR spectra of compounds [Ni(L)(2)](1-),
      [M(L(Bu))(2)](1-) (M = Ni, Pt, Co, Cu). Experimental values of dimensionless
      normal coordinate displacements in excited states have been determined by fitting
      of rR spectra together with the absorption band shape, based on the time
      dependent theory of Heller. Time-dependent density functional theory (TD-DFT) and
      multireference post-Hartree-Fock ab initio calculations, using the difference
      dedicated configuration interaction (MR-DDCI) method, were carried out to
      evaluate dimensionless normal coordinate displacements quantum chemically. The
      calculations show encouraging agreement with the experimental values. The large
      distortions along several normal modes led to significant vibronic broadening of
      IVCT and LMCT bands, and the broadening was accounted for in the deconvolution of
      the absorption spectra. The presence of an intense rR band around approximately
      1100 cm(-1) was found to be a reliable marker for the presence of sulfur-based
      radicals.

PMID- 16569022
TI  - Molecular wiring of nanocrystals: NCS-enhanced cross-surface charge transfer in
      self-assembled Ru-complex monolayer on mesoscopic oxide films.
AB  - We report on rapid ambipolar cross-surface charge transfer within self-assembled
      monolayers (SAM) of the heteroleptic Ru-complexes cis-RuLL'(NCS)(2) (L = 2,2'
      bipyridyl-4,4'-dicarboxylic acid, L' = 4,4'-dinonyl-2,2'-bipyridyl) (1) and cis
      RuLL' '(NCS)(2) (L = 2,2'-bipyridyl-4,4'-dicarboxylic acid, L' = 4,4'-dimethyl
      2,2'-bipyridyl) (2) on the surface of mesoscopic insulating oxide films. The
      bipyridyl ligands of the Ru-complex transport electrons, while the NCS groups
      plays a pivotal role in mediating surface confined hole percolation. Molecular
      dynamics calculations show the NCS ligands of 1 and 2 to orient in a fashion that
      enhances the overlap of the HOMOs of neighboring ruthenium complexes. Using ab
      initio Hartree-Fock calculations the electronic coupling matrix element for
      intermolecular hole exchange at the surface is estimated to be 0.13 eV. Cyclic
      voltammetry as well as spectroelectrochemical and impedance measurements
      performed with a series of other Ru-complexes confirmed the control of the cross
      surface charge transfer by the molecular structure. Complex 2 shows the highest
      percolation rate, the surface hole diffusion coefficient being 1.1 x 10(-8)
      cm(2)/s. The effects of the ligand properties, such as denticity, geometry, and
      size, on the intermolecular charge transport are discussed in detail.

PMID- 16569021
TI  - Molecular probe location in reverse micelles determined by NMR dipolar
      interactions.
AB  - The location and interactions of solutes in microheterogeneous environments, such
      as reverse micelles, critically influence understanding of many phenomena that
      utilize probe molecules to characterize properties in chemical, biological, and
      physical systems. The information gained in such studies depends substantially on
      the location of the probe used. Often, intuition leads to the assumption that
      ionic probe molecules reside in the polar water pool of a system. In this work,
      the location of a charged polar transition metal coordination complex in a
      reverse micellar system is determined using NMR spectroscopy. Despite the
      expected Coulomb repulsion between the surfactant headgroups and the negatively
      charged complex, the complex spends significant time penetrating into the
      hydrophobic portion of the reverse micellar interface. These results challenge
      the assumption that ionic probe molecules reside solvated by water in
      microheterogeneous environments and suggest that probe molecule location be
      carefully considered before interpreting data from similar systems.

PMID- 16569023
TI  - Efficient ribosomal peptidyl transfer critically relies on the presence of the
      ribose 2'-OH at A2451 of 23S rRNA.
AB  - The ribosomal peptidyl transferase center is a ribozyme catalyzing peptide bond
      synthesis in all organisms. We applied a novel modified nucleoside interference
      approach to identify functional groups at 9 universally conserved active site
      residues. Owing to their immediate proximity to the chemical center, the 23S rRNA
      nucleosides A2451, U2506 and U2585 were of particular interest. Our study ruled
      out U2506 and U2585 as contributors of vital chemical groups for
      transpeptidation. In contrast the ribose 2'-OH of A2451 was identified as the
      prime ribosomal group with potential functional importance. This 2'-OH renders
      almost full catalytic power to the ribosome even when embedded into an active
      site of six neighboring 2'-deoxyribose nucleosides. These data highlight the
      unique functional role of the A2451 2'-OH for peptide bond synthesis among all
      other functional groups at the ribosomal peptidyl transferase active site.

PMID- 16569024
TI  - Total synthesis and biological evaluation of halipeptins A and D and analogues.
AB  - The marine-derived halipeptins A (1a) and D (1d) and their analogues 3a, 3d and
      4a, 4d were synthesized starting from building blocks 10, 13, 14a or 14d, 15, and
      16. The first strategy for assembling the building blocks, involving a
      macrolactamization reaction to form the 16-membered ring hydroxy thioamide 52d as
      a precursor, furnished the epi-isoleucine analogue (4d) of halipeptin D, whereas
      a second approach involving thiazoline formation prior to macrolactamization led
      to a mixture of halipeptins A (1a) and D (1d) and their analogues 3a, 3d (epimers
      at the indicated site) and 4a, 4d (epimers at the indicated site). The same route
      starting with D-Ala resulted in the exclusive formation of the epimeric
      halipeptin D analogue 3d. The synthesized halipeptins, together with the
      previously constructed oxazoline analogues 5d and 6d, were subjected to
      biological evaluation revealing anti-inflammatory properties for 1a, 1d, and 6d
      while being noncytotoxic against human colon cancer cells (HCT-116).

PMID- 16569025
TI  - Copolymerization kinetics of methyl methacrylate-styrene obtained by PLP-MALDI
      ToF-MS.
AB  - The combination of MALDI-ToF-MS and pulsed laser polymerization has been used to
      study the propagation rate coefficients for the copolymer system styrene-methyl
      methacrylate. For the first time, complete information regarding mode of
      termination, reactivity of photoinitiator-derived radicals, copolymer molecular
      mass, chemical composition, and copolymerization rates is obtained interrelated.
      The polymerizations were carried out in bulk with varying styrene concentrations
      at a temperature of 15.2 degrees C by an excimer pulsed laser with varying
      frequencies. Both chemical composition distributions and molecular weight
      distributions were determined by MALDI-ToF-MS. The data were fitted to the
      implicit penultimate unit model and have resulted in new point estimates of the
      monomer and radical reactivity ratios for the copolymer system styrene-methyl
      methacrylate: r(St) = 0.517, r(MMA) = 0.420, s(St) = 0.296, s(MMA) = 0.262.
      Comparison between Monte Carlo simulations and the obtained results further
      confirmed the very successful combination of pulsed laser copolymerization
      experiments with MALDI-ToF-MS. The obtained results are believed to be the most
      accurate and complete set of copolymerization parameters to date.

PMID- 16569026
TI  - Kinetic resolution displaying zeroth order dependence on substrate consumption:
      copper-catalyzed asymmetric alcoholysis of azlactones.
AB  - Kinetic resolution of 4-alkyl-2-aryl-5-oxo-4,5-dihydrooxazole-4-carboxylic acid
      esters (azlactones 1) were achieved by copper-DTBM-SEGPHOS catalyzed alcoholysis
      reaction with good selectivity (12 examples). Variation of ee of unreacted
      substrates 1 and products 2 with conversion was found to follow the theoretical
      line of zeroth-order kinetic resolution, for which the selectivity profiles and
      graphical analysis were presented for the first time. The efficiency of
      resolution in zeroth-order reaction is higher than first-order reaction. For
      example, the reaction with 1a afforded (S)-1a (99% ee) and (R)-2a (74% ee) at 57%
      conversion, where the k(rel) values were calculated to be 6.7 as zeroth-order
      kinetic resolution and 37 as first-order kinetic resolution.

PMID- 16569027
TI  - Propeller-like hydrogen-bonded banana-melamine complexes inducing helical
      supramolecular organizations.
AB  - The results of the study presented here show a new example of the use of liquid
      crystals and the interactions involved in the mesomorphic state to build up
      complex molecular organizations. We have pursued a design strategy in which
      hydrogen bonding allows the combination of the pi-stacking tendency of melamine
      and the lateral interaction capability of V-shaped molecules, which has been
      extensively demonstrated through nematic, smectic, or columnar mesophases. This
      combination addresses the formation of columnar arrangements with inherent
      helical organization. In this work, nonmesomorphic as well as mesomorphic V
      shaped acids, with a structure similar to banana liquid crystals, have been
      complexed to a 2,4,6-triamino-1,3,5-triazine derivative in a proportion 3 to 1,
      respectively. Hydrogen-bonded supramolecules whose formation and stability in
      solution have been proven by infrared and NMR techniques have been thus obtained.
      DOSY experiments have allowed us to assess in solution the presence of the
      complexes and their tetrameric composition. All the complexes display mesogenic
      ability, and their mesomorphic organization has been studied by X-ray diffraction
      and CD spectroscopy. Results allow us to propose a helical columnar model for the
      mesophase originated from a propeller-like conformation of the supramolecular
      complexes.

PMID- 16569029
TI  - Supercritical CO2 extraction and purification of compounds with antioxidant
      activity.
AB  - Supercritical fluid extraction (SCFE), based on the utilization of a fluid under
      supercritical conditions, is a technology suitable for extraction and
      purification of a variety of compounds, particularly those that have low
      volatility and/or are susceptible to thermal degradation. The interest in SCFE is
      promoted by legal limitations of conventional solvents for food and
      pharmaceutical uses. The physicochemical properties of supercritical CO2 (higher
      diffusivity, lower viscosity, and lower surface tension than conventional
      solvents) facilitate mass transfer and allow an environmentally friendly
      operation. This article presents a comprehensive compilation of data on the
      supercritical CO2 extraction of antioxidant compounds from vegetal materials,
      with particular attention to those of a phenolic nature. Aspects concerning the
      supercritical operation for extraction and fractionation of antioxidants
      compounds are considered, including equilibrium solubility of pure compounds and
      effects of the operational conditions on the antioxidant activity of isolated
      fractions. The data are compared to those reported for synthetic antioxidants and
      natural extracts obtained by conventional solvent extraction from vegetal
      matrices.

PMID- 16569030
TI  - Quantitation of toxic arsenic species and arsenobetaine in Pacific oysters using
      an off-line process with hydride generation-atomic absorption spectroscopy.
AB  - An off-line process-based speciation technique was devised here to quantitatively
      determine toxic inorganic arsenic (iAs), methylarsonic acid (MA), dimethylarsinic
      acid (DMA), and the dominant, albeit virtually nontoxic, arsenobetaine (AB) in
      Pacific oysters (Crassostrea gigas). Oysters were extracted with fresh methanol
      water (8+2), and this was replicated three times. They were then evaporated to
      near dryness and subsequently redissolved in pure water; defatting was then
      performed with a C18 cartridge. The trace hydride active arsenic species, that
      is, iAs, MA, and DMA, in the defatted solutions were determined with a sensitive
      hydride generation-packed coldfinger trap-atomic absorption spectrometric (HG
      PCFT-AAS) coupled system. The arsenicals that were desorbed from the cation
      exchange resin (Dowex 50W-X8) in the washings of 4 M NH3 were categorized on the
      basis of AB + DMA. The total quantity of arsenic in the recovered AB + DMA was
      determined with a commercial hydride generation-atomic absorption spectrometric
      (HG-AAS) system, and finally, AB was calculated from (AB + DMA) - DMA. The
      average concentrations of iAs, MA, DMA, AB, and total arsenic (TAs) in the
      oysters collected from six aquacultural sites along the west coast of Taiwan
      were, respectively, 0.15, 0.06, 0.64, 6.93, and 13.74 mg kg(-1) of dry weight. AB
      was the major species, whereas iAs (arsenite + arsenate) were the most toxic
      species, although the iAs made up only approximately 1% of the TAs in the
      oysters. The lifetime target cancer risk, as determined by the concentration of
      iAs on a fresh weight basis in the oysters, was well below the ordinary health
      protection criteria (10(-6)).

PMID- 16569031
TI  - Evaporative light-scattering analysis of sulforaphane in broccoli samples:
      Quality of broccoli products regarding sulforaphane contents.
AB  - Broccoli sulforaphane has received attention as a possible anticarcinogen.
      Sulforaphane analysis is difficult due to the lack of a chromophore for
      spectrometric detection. Hence, we developed a method for determining
      sulforaphane by using high-performance liquid chromatography (HPLC) coupled with
      an evaporative light-scattering detector (ELSD). Sulforaphane was extracted from
      acid-hydrolyzed broccoli samples, followed by solid-phase extraction and reversed
      phase HPLC. Sulforaphane was detected by ELSD and concurrently identified by
      electrospray ionization time-of-flight mass spectrometry. The recovery of
      sulforaphane from broccoli samples was above 95%. The detection limit was 0.5
      mug. The present method was sensitive enough to determine sulforaphane in mature
      broccoli, broccoli sprouts, and commercial broccoli products. Sulforaphane
      concentration in broccoli sprout (1153 mg/100 g dry weight) was about 10 times
      higher than that of mature broccoli (44-171 mg/100 g dry weight). Therefore, the
      broccoli sprout is recommended as a source of sulforaphane-rich products. In
      contrast, we found that sulforaphane could not be detected in most of broccoli
      products, suggesting present commercial broccoli products having low quality.

PMID- 16569032
TI  - Determination of usnic acid in lichen toxic to elk by liquid chromatography with
      ultraviolet and tandem mass spectrometry detection.
AB  - Usnic acid is unambiguously confirmed by tandem mass spectrometry (MS/MS) in
      tumbleweed shield lichen, Xanthoparmelia chlorochroa. The lichen contains 2%
      usnic acid by liquid chromatography with UV quantification at 282 nm. The UV
      linear range for usnic acid quantification is from its 4 ng limit of detection to
      2 microg injected. UV signal saturation is recognized by distortion of the usnic
      acid UV spectrum. Positive ion electrospray-tandem mass spectrometry offers no
      similar means to recognize quantification data recorded above the linear range of
      electrospray. Electrospray ionization capacity and matrix effects limit the
      reliability of tandem mass spectrometry quantification. The combination of UV
      quantification and MS confirmation provides a reliable analytical method for
      measuring usnic acid levels in plant material.

PMID- 16569033
TI  - Rapid determination of fumonisin B1 in food samples by enzyme-linked
      immunosorbent assay and colloidal gold immunoassay.
AB  - A rapid enzyme-linked immunosorbent assay (ELISA) test (microwell plate) and a
      membrane-based colloidal gold immunoassay in flow-through and lateral-flow
      formats for the rapid detection of fumonisin B1 (FB1) were developed. The rapid
      microwell assay can be completed within 20 min with the detection limit of 0.5 +/
      0.2 microg/L. Membrane-based colloidal gold immunoassays had a visual detection
      limit of 1.0 microg/L for FB1 with the detection time of <10 min. Matrix
      interference was eliminated by 15-fold dilutions of methanol extracts with
      buffer. These immunoassays can be used as quantitative or qualitative tools for
      the rapid detection of FB1 residues in 10-20 min on-site.

PMID- 16569034
TI  - A sensitive enzyme-linked immunosorbent assay for detecting carcinogenic
      aristolochic acid in herbal remedies.
AB  - Aristolochic acid, a naturally occurring nephrotoxin and rodent carcinogen, has
      been associated with the development of various nephropathies in humans.
      Developing a sensitive and rapid method to screen the aristolochic acid levels in
      herbal remedies is urgent for protecting public health. Polyclonal antibodies for
      aristolochic acid were generated from rabbits after the animals had been
      immunized with either aristolochic acid-ovalbumin (OVA) or aristolochic acid
      keyhole limpet hemocyanin (KLH). A competitive indirect enzyme-linked
      immunosorbent assay (ciELISA) and a competitive direct enzyme-linked
      immunosorbent assay (cdELISA) were used for the characterization of the
      antibodies and for analysis of aristolochic acid contaminated in herbal medicine
      and diet pills. The antibody titers in the serum of rabbits immunized with
      aristolochic acid-OVA were considerably higher than those from aristolochic acid
      KLH-immunized rabbits. The antibodies from the aristolochic acid-OVA-immunized
      rabbits were further characterized. In the ciELISA with aristolochic acid-KLH as
      the plate-coating antigen, the concentrations of the aristolochic acid mixture,
      aristolochic acid I, and aristolochic acid II that caused 50% inhibition (IC50)
      of binding of antibodies to aristolochic acid-KLH were found to be 1.2, 0.7, and
      18 ng/mL, respectively. When 0.25-5 microg/g of standard aristolochic acid was
      spiked to ground lotus seeds and then extracted with 0.01 M phosphate-buffered
      saline, the recovery rate was found to be 86.5% in the ciELISA. Analysis of
      aristolochic acid in herbal medicine and diet pills with ciELISA showed that 10
      of the 12 examined samples were contaminated at levels from 0.6 to 655 microg/g.
      The presence of aristolochic acid was also confirmed by the high-performance
      liquid chromatography method.

PMID- 16569035
TI  - Development of multianalyte flow-through and lateral-flow assays using gold
      particles and horseradish peroxidase as tracers for the rapid determination of
      carbaryl and endosulfan in agricultural products.
AB  - Membrane-based competitive immunoassays using gold particles and horseradish
      peroxidase (HRP) as tracers in flow-through and lateral-flow formats for
      multianalysis of carbaryl and endosulfan were developed. For gold-based
      immunoassay, membrane strips were coated with goat anti-rabbit IgG (control line)
      and carbaryl hapten-ovalbumin (OVA) and endosulfan hapten-OVA (test lines). The
      visual detection limits for carbaryl and endosulfan were 100 and 10 microg/L in
      gold-based assays, respectively. For immunoassay using HRP as tracer, anti
      carbaryl and anti-endosulfan antibodies were separately coated on the membrane as
      test lines, and the visual detection limits were 10 microg/L for carbaryl and 1
      microg/L for endosulfan. The developed assays used gold particles and HRP as
      labels, respectively; 10 times enhancement in the visual detection limit using
      HRP label was obtained in the study. Matrix interference was eliminated by
      appropriate dilution of sample extracts with buffer. For the validation of the
      multianalyte assay, the samples were screened by multianalyte gold-based assay
      and confirmed by HPLC for carbaryl determination and by GC for endosulfan
      determination. The results of multianalyte gold-based flow-through assay for the
      determination of carbaryl and endosulfan were in good agreement with the results
      of instrumental analysis (HPLC with ultraviolet detection and GC with electron
      capture detection). The developed multianalyte immunoassays for which the results
      were interpreted visually can be used as convenient qualitative tools for on-site
      rapid screening of carbaryl and endosulfan simultaneously in agricultural
      products.

PMID- 16569036
TI  - Fast analysis of sugars, fruit acids, and vitamin C in sea buckthorn (Hippophae
      rhamnoides L.) varieties.
AB  - A fast, one-step gas chromatographic method was developed to analyze
      trimethylsilyl (TMS) derivatives of sugars, fruit acids, and ascorbic acid in sea
      buckthorn (Hippohae rhamnoides L.) berries. The method was applied to berry press
      juice of sea buckthorn of different origins grown in Finland during the 2003 and
      2004 seasons. The method gave reliable results for D-fructose, D-glucose, ethyl-D
      glucose, and malic, quinic, and ascorbic acids, which are the major sugars and
      acids in sea buckthorn juice. For the first time in sea buckthorn and evidently
      in any berry, the presence of ethyl beta-D-glucopyranoside is reported. The
      structure of ethyl glucose was verified by high-performance liquid chromatography
      (HPLC), gas chromatography (GC), MS, and NMR analyses of both the isolated and
      the synthesized compounds. In the GC method, vitamin C was analyzed as ascorbic
      acid only, and dehydroascorbic acid was thus not taken into account.

PMID- 16569037
TI  - Effects of beer and hop on ionotropic gamma-aminobutyric acid receptors.
AB  - Beer induced the response of the ionotropic gamma-aminobutyric acid receptors
      (GABA(A) receptors) expressed in Xenopus oocytes, indicating the presence of
      gamma-aminobutyric acid (GABA)-like activity. Furthermore, the pentane extract of
      the beer, hop (Humulus lupulus L.) oil, and myrcenol potentiated the GABA(A)
      receptor response elicited by GABA. The GABA(A) receptor responses were also
      potentiated by the addition of aliphatic esters, most of which are reported to be
      present in beer flavor. Aliphatic esters showed the tendency to decrease in the
      potentiation of the GABA(A) receptor response with an increase in their carbon
      chain length. When myrcenol was injected to mice prior to intraperitoneal
      administration of pentobarbital, the pentobarbital-induced sleeping time of mice
      increased additionally. Therefore, the beer contained not only GABA-like activity
      but also the modulator(s) of the GABA(A) receptor response.

PMID- 16569038
TI  - Triterpene saponins from the roots of Medicago hybrida.
AB  - Fourteen triterpene saponins (1-14) have been isolated from the roots of Medicago
      hybrida and their structures elucidated by FAB-MS and NMR analysis. Two of them
      are new compounds and were identified as hederagenin 3-O-[alpha-L
      rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-28-O
      beta-D-glucopyranoside (7) and oleanolic acid 3-O-[beta-D-galactopyranosyl(1-->2)
      beta-D-glucuronopyranosyl]-28-O-[alpha-L-rhamnopyranosyl(1-->4)-beta-D
      glucopyranoside] (14). Seven saponins being mono- and bidesmosides of hederagenin
      (1, 5, 6, 9), one bidesmoside of bayogenin (2), and two bidesmosides of
      2beta,3beta-dihydroxyolean-12-en-23-al-28-oic acid (11) and oleanolic acid (13)
      are known compounds but not previously reported as saponin constituents of
      Medicago, whereas five other saponins, being mono- and bidesmosides of
      medicagenic acid (3, 4, 8, 10, 12), and one monodesmoside of hederagenin (8) have
      been previously isolated from other Medicago species. The presence of 2beta,3beta
      dihydroxyolean-12-en-23-al-28-oic acid might represent an interesting
      intermediate in the biosynthesis of these substances.

PMID- 16569039
TI  - Evaluation of allelopathic potential and quantification of momilactone A,B from
      rice hull extracts and assessment of inhibitory bioactivity on paddy field weeds.
AB  - Rice (Oryza sativa L.) hull extracts were used in a bioassay to evaluate the
      allelopathic potential of rice on the germination and growth of barnyard grass
      (Echinochloa crus-galli P. Beauv. var. oryzicola Ohwi), to quantify momilactone A
      and B levels in rice hull germplasm and to assess the inhibitory bioactivity of
      momilactone A and B as a potential natural source of herbicide for weed control
      in paddy fields. Four varieties of weeds including E. crus-galli P. Beauv. var.
      oryzicola Ohwi, Monochoria vaginalis var. plantaginea, Scirpus juncoides, and
      Eleocharis kuroguwai were tested in the paddy field. Of 99 rice varieties, the
      top five including Noindari exhibited inhibition effects greater than 50% in
      average inhibition of dry weight (AIDW). Noindari among them exerted the
      strongest effect (55.6%). The next five in the ranking exhibited inhibition
      effects of greater than 40%. Also, 46 varieties had inhibition effects between 20
      and 40%, and 29 varieties had inhibition effects greater than 10%. Fourteen
      varieties had very low inhibitory effects (less than 10%), the lowest of which
      was Heunbe (4.7%). These varieties showed a mean inhibition of 19.8% for
      germination rate (GR), 9.9% for germination percentage (GP), 16.6% for leaf dry
      weight (LDW), 38.9% for straw dry weight (SDW), and 26.8% for root dry weight
      (RDW). Rice varieties were classified into six categories based on their total
      momilactones (TMs) (momilactone A + momilactone B). The highest level of
      momilactone A was found in the Baekna rice variety (34.7 microg g(-1)), and
      Baekgwangok contained the highest level of momilactone B (37.8 microg g(-1)). In
      allelopathic potential with genetic properties and morphological characteristics,
      the total inhibition rate (TIR) was 18.3% for Korean rice varieties, 19.0% for
      middle maturing varieties, 17.8% for colorless hull varieties, 18.3% for awn
      varieties, and 19.0% for colorless awn varieties. In addition, Korean varieties
      showed higher TMs (4.5 microg g(-1)) as compared with varieties that were late
      maturing (4.4 microg g(-1)), had colorless hulls (4.1 microg g(-1)), awns (4.7
      microg g(-1)), and colorless awns (4.8 microg g(-1)). Momilactone A levels were
      generally higher than momilactone B levels. Total inhibition rates on barnyard
      grass correlated with average inhibitions of germination (AIG) (r2 = 0.62***),
      AIDW (r2 = 0.92***), and were affected by the inhibition rate of GP (r2 =
      0.57***). Regions of origin for rice varieties correlated with the AIG (r2 = 
      0.23***), and maturing time showed a positive correlation with SDW (r2 = 0.15**)
      and RDW (r2 = 0.19**). Levels of momilactones were also correlated with the
      region of origin (r2 = -0.32***), maturing time (r2 = 0.13***), and awns
      (momilactone A, r2 = 0.23***; momilactone B, r2 = 0.14**), suggesting that rice
      varieties with awns, Korean varieties, and varieties with later maturing times
      contain higher levels of momilactone. Also, the investigation of the momilactone
      A and B bioactivity (0, 250, 500, 1000, 2000, and 4000 g a.i./ha) for weed
      control in paddy fields indicated that momilactones A and B exhibited no toxicity
      (0 in all concentrations) against rice plants, and the inhibitory bioactivity on
      weeds with momilactone A was higher than that of momilactone B. When compared
      with no momilactone control, the highest inhibitory effect (50%) on E. crus-galli
      P. Beauv. var. oryzicola Ohwi was shown on the 14th day after the application of
      momiactone A. The inhibitory effect increased with the concentration of the
      compound from 250 to 4000 g a.i./ha. Furthermore, momilactone A showed greater
      suppression than momliactone B toward toward E. crus-galli P. Beauv. var.
      oryzicola Ohwi, M. vaginalis var. plantaginea, S. juncoides, and E. kuroguwai. In
      broad weed species, momilactone A showed the highest inhibitory effect (90% in
      4000 g a.i./ha) on S. juncoides, 14 days after the application as compared with
      no momilactone control. Further studies on allelopathic effects and momilactones
      from the germplasm of rice varieties using genetic properties and morphological
      characteristics may facilitate the development of rice varieties with higher
      allelopathic potential. Momilactones A and B present in rice hulls may serve as a
      potential natural herbicide source for weed control in paddy fields reducing the
      dependence on synthetic herbicides.

PMID- 16569040
TI  - Antioxidant activity of diterpenes and polyphenols from Ophryosporus heptanthus.
AB  - The antioxidant activity of 14 compounds (1-14) isolated from the ether and
      butanolic extracts of the aerial parts of Ophryosporus heptanthus has been
      assayed using a beta-carotene bleaching method and the DPPH technique. Compounds
      1 and 13 showed the most potent antioxidant activity. Their structures have been
      established by spectroscopic techniques (mainly NMR). Compounds 7 and 12 are new
      natural products, and their structures have been confirmed by chemical synthesis.

PMID- 16569041
TI  - Tetramethylated dimeric procyanidins are detected in rat plasma and liver early
      after oral administration of synthetic oligomeric procyanidins.
AB  - Procyanidins (PC) are of great interest in nutrition because they account for a
      major fraction of the total flavonoids ingested in Western diets and have health
      benefits in humans. However, it remains unknown which species of PC, namely,
      monomers, oligomers, or aromatic acid derivatives of gut microflora, are
      responsible for their beneficial effects in vivo. The high molecular complexity
      of PC extracts and PC-rich foods is a major problem in absorption studies. To
      circumvent this difficulty, we have synthesized oligomeric PC consisting of (-)
      epicatechin units linked by ethyl bridges. The synthetic PC (SPC) only contains
      dimers, trimers, tetramers, and nanomers. After oral gavage of this SPC (200
      mg/kg body weight) to male Wistar rats, tetramethylated dimeric PC (TDPC) were
      detected in plasma and liver. TDPC were detected in plasma as soon as 1 h after
      intake, reaching maximum concentrations (14 mg/L) 2 h after gavage. At this time,
      liver contained as much as 15 mug of TDPC per gram of tissue. In conclusion,
      orally administered dimeric PC are rapidly absorbed and internally methylated in
      rats. To our knowledge, this is the first time that methylated dimeric PC have
      been detected in plasma and liver. We consider that plasma and liver
      concentrations of TDPC are sufficient to exert a hormone-like effect and,
      therefore, that PC dimers are good candidates as agents of the biological
      activities of PC extracts and PC-rich foods.

PMID- 16569042
TI  - Evaluation of antiherpetic activity and genotoxic effects of tea catechin
      derivatives.
AB  - This study evaluated the antiherpetic activity and genotoxicity of catechin and
      some of its derivatives using the MTT colorimetric and comet assays,
      respectively. The results showed that all compounds have antiviral activity with
      selective indices varying from 1.3 to 13, depending on the tested HSV-1 strain.
      It was observed that the same concentration of the compounds that protects the
      Vero cells against the viral infection induces genotoxicity. It was also observed
      that the molecules containing three hydroxyl groups on the B ring caused less DNA
      damage and showed better antiviral effect than those with two hydroxyls on the
      same ring, but if there is an additional galloyl group, these results can be
      altered. The bioavailability and stereochemistry could be related to the
      antiviral and genotoxic effects detected.

PMID- 16569043
TI  - Study on the nitric oxide scavenging effects of ginseng and its compounds.
AB  - In this study, an in vitro nitric oxide (*NO)-generating system was used to
      investigate the *NO-scavenging effects of methanolic extracts of white ginseng
      (Panax ginseng C.A. Meyer), red ginseng, and sun ginseng and several ginsenosides
      and phenolic compounds. Sun ginseng extract showed the strongest activity among
      the three ginseng extracts. None of the ginsenosides used in this experiment
      showed *NO-scavenging activity, but the phenolic compounds, such as p-coumaric
      and vanillic acids, and maltol inhibited *NO production in a concentration
      dependent manner. Moreover, maltol levels markedly increased by heat processing.
      Therefore, the enhanced *NO-scavenging activity of ginseng by heat processing was
      closely related to phenolic acids and the increased content of maltol.

PMID- 16569044
TI  - Effect of a tomato-based drink on markers of inflammation, immunomodulation, and
      oxidative stress.
AB  - Regular consumption of tomato and its products is being consistently associated
      with lower risk of several types of cancer and, to a lesser extent, coronary
      heart disease. Among the many tomato components credited with healthful
      properties, carotenoids and particularly lycopene are being actively
      investigated. Given the recognized role of immune/inflammatory processes in
      atherogenesis, the effects of a tomato-based drink (Lyc-o-Mato), which was
      previously shown to afford DNA protection from oxidative stress, on the
      modulation of immune and inflammatory markers (by enzyme immunoessay), on basal
      lymphocyte DNA damage (by comet assay), and on F2-isoprostane excretion (by LC
      MS/MS), were investigated in 26 healthy young volunteers. In a placebo
      controlled, double-blind, crossover study, Lyc-o-Mato (5.7 mg of lycopene, 3.7 mg
      of phytoene, 2.7 mg of phytofluene, 1 mg of beta-carotene, and 1.8 mg of alpha
      tocopherol) or a placebo drink (same taste and flavor, but devoid of active
      compounds) were given for 26 days, separated by a wash-out period. During the
      study subjects maintained their habitual, hence unrestricted, diet. TNF-alpha
      production by whole blood was 34.4% lower after 26 days of drink consumption,
      whereas the other parameters were not significantly modified by the treatment. In
      turn, modest effects of the regular intake of a tomato drink, providing small
      amounts of carotenoids, were found on the production of inflammatory mediators,
      such as TNF-alpha, in young healthy volunteers. Future intervention trials in
      subjects with low carotenoid status and/or compromised immune system will resolve
      the issue of whether carotenoids modulate immune parameters in humans.

PMID- 16569045
TI  - Proteolysis in model sourdough fermentations.
AB  - Model wheat doughs started with six different lactic acid bacteria (LAB), with or
      without a commercial baker's yeast culture, were used to study proteolysis in
      sourdough fermentations. Cell counts, pH, and free amino acid concentration were
      measured. Sequential extraction of dough samples was performed to separate wheat
      proteins. The salt-soluble protein fraction (albumins and globulins) was analyzed
      by RP-HPLC and SDS-PAGE, whereas propanol-soluble (gliadins) and insoluble
      (glutenins) protein fractions were analyzed by SDS-PAGE only. Multivariate
      statistical methods were used for the analysis of results. The presence of yeasts
      and LAB affected RP-HPLC and SDS-PAGE patterns of the salt-soluble fraction in a
      complex way. The only changes in the gluten proteins that could be related to the
      presence of LAB were the appearance of new protein fragments (20 and 27 kDa) from
      gliadins and the degradation of high molecular weight glutenin subunits.

PMID- 16569046
TI  - Performance of crude olive pomace oil and soybean oil during carotenoid
      production by Blakeslea trispora in submerged fermentation.
AB  - Crude olive pomace oil (COPO) and crude soybean oil (CSO), two low-cost carbon
      sources, were examined as cosubstrates of glucose for carotenoid production by
      Blakeslea trispora. Results were compared to those obtained in glucose as a sole
      carbon source (medium 1) and glucose plus the respective end-line refined oil
      counterparts. Microbial growth in the presence of oils resulted in an increase in
      total carotenoid production. The performance of crude oils was better than that
      of the respective refined forms. Carotenoid production depended on both type and
      added oil amount. An increase in added oil amount did not necessarily favor
      carotenoid accumulation. The addition of 10 g oil/L of substrate stimulated
      carotenoid synthesis, mainly that of beta-carotene, more than 14 (COPO) and 40
      times (CSO) in comparison to that observed in medium 1. The maximum total
      carotenoid content (as mg beta-carotene per g of biomass dry weight) was 75
      (COPO) and 235 mg (CSO), respectively. Growth, substrate assimilation, and lipid
      accumulation-degradation also depended on the presence of oil in the substrate.

PMID- 16569047
TI  - In vitro study of microencapsulated isoflavone and beta-galactosidase.
AB  - This study was designed to find the optimum conditions for isoflavone or beta
      galactosidase microencapsulation and to examine the release efficiency of
      microcapsules in simulated gastrointestinal conditions. Coating materials were
      either medium-chain triacylglycerol (MCT) or polyglycerol monostearate (PGMS).
      The highest rate of microencapsulation was found at 15:1 (w/w) ratio of MCT to
      isoflavone or beta-galactosidase as 70.2 or 75.4%, respectively. When PGMS was
      used as the coating material, 91.5% beta-galactosidase was microencapsulated with
      15:1 mixture (w/w). In vitro study, less than 6.3-9.3% of isoflavone was released
      in simulated gastric fluid (pH 2-5) during 1 h incubation. Comparatively,
      isoflavone release increased dramatically to 87.8% at pH 8 for 1 h incubation in
      simulated intestinal fluid and was maintained thereafter. The release of beta
      galactosidase showed a similar trend to that of isoflavone. It appeared in the
      range of 12.3-15.2% at pH 2-5; however, it increased significantly to 80.6% as
      the highest value at pH 8. Among the released isoflavones, 53.5% was converted
      into the aglycone form of isoflavone at pH 8 for 3 h incubation. The present
      study indicated that isoflavone or beta-galactosidase could be microencapsulated
      with fatty acid esters and released effectively in simulated intestinal
      condition.

PMID- 16569048
TI  - Hydrolysis kinetic parameters of DP 6, 7, 8, and 9-12 fructooligosaccharides
      (FOS) of onion bulb tissues. effect of temperature and storage time.
AB  - The objective of this study was to report on the variation of DP 6 isomers (6b,
      6c + 6d1 + 6d2), 7a, 8, and 9-12 fructooligosaccharides (FOS) and their
      hydrolysis parameters [percent hydrolysis, consumption rate, hydrolysis rate
      constant (k(obsd)), and half-life time (t(1/2))] in onion bulb tissues stored for
      6 months at 10, 15, or 20 degrees C. The hydrolysis of DP 6 isomers, 7a, and 8
      ranged from 74 to 85%, whereas that of DP 9-12 averaged 86%. The consumption rate
      of 6b, 6c + 6d1 + 6d2, 7a, 8, and -12 averaged 25, 58, 38, 26, and 48 microg/g of
      fresh weight per week, respectively. The k(obsd) showed large variation from 53 x
      10(-3) week(-1) (lowest value) to 92 x 10(-3) week(-1) (highest value), whereas
      the half-life t(1/2) of the different FOS ranged between 7.5 and 13.1 weeks. DP
      6b isomers increased during the first month, and then the content decreased
      sharply during the second month at 20 degrees C but remained stable during the
      last 4 months, whereas at 10 and 15 degrees C, 6b decreased progressively from
      the first to the six month. In contrast, DP 6c + 6d1 + 6d2 decreased abruptly
      within the first 3 months at 10, 15, and 20 degrees C; however, during the last 3
      months they remained stable, ranging between 0.32 and 0.39. Variation of DP 7a,
      8, and 9-12 FOS was close to that of DP 6 FOS isomers. DP 7a increased slightly
      during the first month, and afterward 7a started decreasing progressively during
      the last 5 months. DP 8 FOS showed a similar pattern independent of temperature
      regime: they increased slightly within the first month, but from the second
      month, DP 8 began decreasing progressively and continued decreasing to the sixth
      month. DP 9-12 FOS also varied similarly to DP 6c + 6d1 + 6d2. They decreased
      sharply within the first 2 months, and during the last 4 months, they continued
      to decrease slowly. Surprisingly, these variations occurred independently of
      temperature regimes and were affected only by storage duration. It was concluded
      that highly polymerized FOS are preferably hydrolyzed rather than low DP FOS
      isomers because they have a relatively high content of fructosyl end chains.

PMID- 16569049
TI  - Carotenoid content of 50 watermelon cultivars.
AB  - The lycopene content of 50 commercial cultivars of seeded and seedless red
      fleshed watermelons was determined. Scanning colorimetric and spectrophotometric
      assays of total lycopene were used to separate watermelon cultivars into low (<50
      mg/kg fw), average (50-70 mg/kg fw), high (70-90 mg/kg fw), and very high (>90
      mg/kg fw). Cultivars varied greatly in lycopene content, ranging from 33 to 100
      mg/kg. Most of the seeded hybrid cultivars had average lycopene contents. Sixteen
      of the 33 seedless types had lycopene contents in the high and very high ranges.
      All-trans-lycopene was the predominant carotenoid (84-97%) in all watermelon
      cultivars measured by high-performance liquid chromatography, but the germplasm
      differed in the relative amounts of cis-lycopene, beta-carotene, and phytofluene.
      Red-fleshed watermelon genotypes vary extensively in carotenoid content and offer
      opportunities for developing watermelons with specifically enhanced carotenoids.

PMID- 16569050
TI  - Structural characterization of lignin from leaf sheaths of "dwarf cavendish"
      banana plant.
AB  - Dioxane lignin (DL) isolated from leaf sheaths of banana plant (Musa acuminata
      Colla var. cavendish) and in situ lignin were submitted to a comprehensive
      structural characterization employing spectroscopic (UV, FTIR, solid state 13C CP
      MAS NMR, liquid state 13C and 1H NMR) and chemical degradation techniques
      (permanganate and nitrobenzene oxidation). Results obtained showed that banana
      plant leaf sheath lignin is of HGS type with a molar proportion of p
      hydroxyphenyl (H)/guaiacyl (G)/syringyl (S) units of 12:25:63. Most of the H
      units in DL are terminal phenolic coumarates linked to other lignin substructures
      by benzyl and Cgamma-ester bonds in contrast to ferulates that are mainly ether
      linked to bulk lignin. It is proposed that banana plant leaf sheath lignin is
      chemically bonded to suberin-like components of cell tissues by ester linkages
      via essentially hydroxycinnamic acid residues. beta-O-4 structures (0.31/C6), the
      most abundant in DL, comprise mainly S units, whereas a significant proportion of
      G units is bonded by beta-5, 5-5', and 4-O-5' linkages contributing to ca. 80% of
      condensed structures in DL.

PMID- 16569051
TI  - Antioxidant composition in cherry and high-pigment tomato cultivars.
AB  - Fourteen cultivars of cherry tomatoes and four cultivars of high-pigment tomato
      hybrids were cultivated in southern Italy, and the red-ripe fruits were analyzed
      for their content in different classes of antioxidants and for their antioxidant
      activity. Among the different cultivars, significant differences were found
      between lycopene, beta-carotene, alpha-tocopherol, vitamin C (ascorbic acid and
      dehydroascorbic acid), and total phenolic and flavonoid contents. LS203 and
      Corbus appear to be the cultivars with the highest content of lipophilic and
      hydrophilic antioxidants among cherry tomatoes, respectively. All cultivars of
      high-pigment tomato hybrids showed an expected exceptionally high lycopene
      content. Among them, the highest content of lipophilic and hydrophilic
      antioxidants was found in cv. HLY 13. Hydrophilic and lipophilic antioxidant
      activities were both significantly influenced by genotype. Such results highlight
      an existing unexploited variability in tomato germplasm and stress the need to
      evaluate the biodiversity and to support conventional breeding programs to
      improve tomato nutritional value.

PMID- 16569052
TI  - Influence of fertilization, mulch color, early forcing, fruit order, planting
      date, shading, growing Environment, and genotype on the contents of selected
      phenolics in strawberry (Fragaria x ananassa Duch.) fruits.
AB  - The influence of agricultural practices (fertilization, mulch color, early
      forcing, and planting date), environment (light and growing area), cultivar, and
      fruit order on the selected phenolic content and antioxidant activity in
      strawberry (Fragaria x ananassa Duch.) fruits was studied. Three different levels
      of fertilization were given to plants in the fertilization experiment. The lowest
      fertilization level increased the contents of flavonols and ellagic acid from 19
      to 57%. Between cultivars, up to 4-fold differences were found in the flavonol
      content, and it also varied according to growing environment. Planting date in
      glasshouse production was important for the phenolic content, and a statistically
      significant interaction was found between planting date and fruit order. Fruit
      order caused at highest 1.5-2.0-fold differences in the contents of phenolics.
      Interestingly, compared with other phenolics, anthocyanins were affected
      differently by many factors. Thus, the findings show that minor cultivation
      changes can increase the content of phenolics, especially in under-glass
      production where conditions can be easily manipulated.

PMID- 16569053
TI  - New insights on glyphosate mode of action in nodular metabolism: Role of
      shikimate accumulation.
AB  - The short-term effects of the herbicide glyphosate (1.25-10 mM) on the growth,
      nitrogen fixation, carbohydrate metabolism, and shikimate pathway were
      investigated in leaves and nodules of nodulated lupine plants. All glyphosate
      treatments decreased nitrogenase activity rapidly (24 h) after application, even
      at the lowest and sublethal dose used (1.25 mM). This early effect on nitrogenase
      could not be related to either damage to nitrogenase components (I and II) or
      limitation of carbohydrates supplied by the host plant. In fact, further exposure
      to increasing glyphosate concentrations (5 mM) and greater time after exposure (5
      days) decreased nodule starch content and sucrose synthase (SS; EC 2.4.1.13)
      activity but increased sucrose content within the nodule. These effects were
      accompanied by a great inhibition of the activity of phosphoenolpyruvate
      carboxylase (PEPC; EC 4.1.1.31). There were remarkable and rapid effects on the
      increase of shikimic and protocatechuic (PCA) acids in nodules and leaves after
      herbicide application. On the basis of the role of shikimic acid and PCA in the
      regulation of PEPC, as potent competitive inhibitors, this additional effect
      provoked by glyphosate on 5-enolpyruvylshikimic-3-phosphate synthase enzyme
      (EPSPS; EC 2.5.1.19) inhibition would divert most PEP into the shikimate pathway,
      depriving energy substrates to bacteroids to maintain nitrogen fixation. These
      findings provide a new explanation for the effectiveness of glyphosate as a
      herbicide in other plant tissues, for the observed differences in tolerance among
      species or cultivars, and for the transitory effects on glyphosate-resistant
      transgenic crops under several environmental conditions.

PMID- 16569054
TI  - Relative activity of a tobacco hybrid expressing high levels of a tobacco anionic
      peroxidase and maize ribosome-inactivating protein against Helicoverpa zea and
      Lasioderma serricorne.
AB  - Tobacco (Nicotiana tabacum) plants grown from seed obtained by crossing a tobacco
      line that expressed an activated maize ribosome-inactivating protein (RIP) with a
      line that overexpressed tobacco anionic peroxidase were tested for their effects
      on corn earworm Helicoverpa zea and cigarette beetle Lasioderma serricorne larvae
      as compared to the wild-type plant cross. Significant feeding reductions were
      noted for transgenic plants expressing both resistance proteins as compared to
      wild-type plants for both H. zea and L. serricorne. Significant increases in
      mortality were also noted for those insects fed on the transgenic cross as
      compared to wild-type plants in some cases. Levels of both peroxidase and maize
      RIP were significantly higher in transgenic as compared to wild-type plants
      (which did not produce maize RIP). The degree of feeding was significantly
      negatively correlated with the level of RIP or peroxidase individually.

PMID- 16569055
TI  - Imazethapyr aqueous photolysis, reaction quantum yield, and hydroxyl radical rate
      constant.
AB  - The recent introduction of imidazolinone-tolerant rice varieties allow
      imazethapyr to be used in commercial rice. Little is known about imazethapyr
      photodegradation in the rice field. Laboratory studies were conducted to
      determine the direct and indirect photolysis rates for imazethapyr and to
      evaluate the photolysis of imazethapyr in three rice paddy waters. The reaction
      quantum yield (phi I) for imazethapyr was determined to be 0.023 +/- 0.002, while
      the hydroxyl radical rate constant (K(I)*OH) was 2.8 x 10(13) M(-1) h(-1). These
      results show that imazethapyr is susceptible to both direct and indirect
      photolysis reactions in water. The results also show that imazethapyr photolysis
      in paddy water will be affected by turbidity because of its impact on the
      availability of sunlight to drive direct and indirect photolysis reactions.

PMID- 16569056
TI  - Degradation of chloroacetanilide herbicides by anodic fenton treatment.
AB  - Anodic Fenton treatment (AFT) is an electrochemical treatment employing the
      Fenton reaction for the generation of hydroxyl radicals, strong oxidants that can
      degrade organic compounds via hydrogen abstraction. AFT has potential use for the
      remediation of aqueous pesticide waste. The degradation rates of
      chloroacetanilides by AFT were investigated in this work, which demonstrates that
      AFT can be used to rapidly and completely remove chloroacetanilide herbicides
      from aqueous solutions. Acetochlor, alachlor, butachlor, metolachlor, and
      propachlor were treated by AFT, and parent compound concentrations were analyzed
      over the course of the treatment time. Degradation curves were plotted and fitted
      by the AFT kinetic model for each herbicide, and AFT model kinetic parameters
      were used to calculate degradation rate constants. The reactivity order of these
      five active ingredients toward hydroxyl radical was acetochlor approximately
      metolachlor > butachlor approximately alachlor > propachlor. Treatment of the
      chloroacetanilides by AFT removed the parent compounds but did not completely
      mineralize them. However, AFT did result in an increase in the biodegradability
      of chloroacetanilide aqueous solutions, as evidenced by an increase in the 5-day
      biochemical oxygen demand to chemical oxygen demand ratio (BOD5/COD) to >0.3,
      indicating completely biodegradable solutions. Several degradation products were
      formed and subsequently degraded, although not always completely. Some of these
      were identified by mass spectral analyses. Among the products, isomers of
      phenolic and carbonyl derivatives of parent compounds were common to each of the
      herbicides analyzed. More extensively oxidized products were not detected.
      Degradation pathways are proposed for each of the parent compounds and identified
      products.

PMID- 16569057
TI  - Identification and quantification of polybrominated hexahydroxanthene derivatives
      and other halogenated natural products in commercial fish and other marine
      samples.
AB  - During routine analysis of commercial fish on halogenated pollutants, an unknown
      tribromo component (TriBHD) was initially detected as an abundant peak in sample
      extracts from the Mediterranean Sea. The molecular formula was established to be
      C16H19Br3O by gas chromatography with electron ionization high-resolution mass
      spectrometry (GC/EI-HRMS). GC/EI-MS data were virtually identical with a
      polybrominated hexahydroxanthene derivative (PBHD) previously isolated from an
      Australian sponge species known to occur in the Mediterranean Sea as well. A
      tetrabromo isomer (TetraBHD) was also found in the fish samples. The
      concentrations of TriBHD and other halogenated compounds in commercial fish (sea
      bass, gilt head bream, anchovy, sardine, and salmon) were estimated with
      GC/electron capture detection (ECD). Using the ECD response of trans-nonachlor,
      the concentration of TriBHD reached up to 90 ng/g lipid weight and accounted for
      up to >90% of the concentration of p,p'-DDE, which was the most abundant peak in
      the most samples investigated. On the basis of the GC/ECD response, TetraBHD
      amounted for approximately 1/7 of TriBHD in all fish samples investigated. The
      sample with the highest content was a green-lipped mussel from New Zealand (236
      ng/g lipid weight). The halogenated natural products TBA, Q1, and MHC-1 were also
      present in most of the samples. We assume that the bulk of the residues in fish
      from aquaculture may originate from algae and sponges living in proximity of the
      fish farms. Detection of TriBHD and TetraBHD in blubber of a monk seal (Monachus
      monachus) suggests that both HNPs may reach the top predators of food webs and
      thus also humans.

PMID- 16569058
TI  - Degradation of pesticides in nursery recycling pond waters.
AB  - Recycling or collection ponds are often used in outdoor container nursery
      production to capture and recycle runoff water and fertilizers. Waters in
      recycling ponds generally have high concentrations of nutrients, pesticides, and
      dissolved organic matter, as well as elevated salinity and turbidity. Little is
      known about pesticide degradation behavior in the unique environment of nursery
      recycling ponds. In this study, degradation of four commonly used pesticides
      diazinon, chlorpyrifos, chlorothalonil, and pendimethalin in waters from two
      nursery recycling ponds was investigated at an initial pesticide concentration of
      50 microg/L. Results showed that the persistence of diazinon and chlorpyrifos
      appeared to be prolonged in recycling pond waters as compared to surface
      streamwaters, possibly due to decreased contribution from biotic transformation,
      while degradation of chlorothalonil and pendimethalin was enhanced. Activation
      energies of biotic degradation of all four pesticides were lower than abiotic
      degradation, indicating that microbial transformation was less affected by
      temperature than chemical transformation. Overall, the pesticide degradation
      capacity of recycling ponds was better buffered against temperature changes than
      that of surface streamwaters.

PMID- 16569059
TI  - Orthonasal and retronasal perception of some green leaf volatiles used in
      beverage flavors.
AB  - Orthonasal perception of six green leaf volatiles (GLVs) classified only hexanal,
      (E)-2-hexenal, and (Z)-3-hexen-1-yl formate as green. (Z)-3-Hexen-1-yl hexanoate
      and (Z)-3-hexen-1-yl 3-methylbutyrate were more floral, and (Z)-3-hexen-1-yl
      acetate fell between the two groups. For retronasal perception, classification
      along a bipolar green-fruity scale is proposed for describing these GLVs. Data
      from grouping and dissimilarity tests as well as from sensory profiling show
      green character for these compounds in standard beverage bases having low Brix or
      high acidity. As the Brix value increases (or acidity decreases) within the
      limits encountered in commercial beverages, the character becomes fruity. Several
      tastant-dependent changes in intensity scores for retronasal descriptors were
      shown to occur for mixtures of GLVs. The GLVs did not affect intensity scores for
      gustatory descriptors.

PMID- 16569060
TI  - Sweetener/sweetness-induced changes in flavor perception and flavor release of
      fruity and green character in beverages.
AB  - Green leaf volatile (GLV) mixtures, commercial orange flavors, and commercial
      strawberry flavors were applied to beverage bases in which concentrations of
      citric acid as well as a sweetener (sucrose or aspartame/acesulfame-K) were
      varied. Sensory profiling showed that flavor-specific fruity character increased
      as perceptible sweetness increased, independent of whether the sweetness resulted
      from sucrose (a change from 9 to 12 Brix) or aspartame/acesulfame-K (a change
      from 0.2 to 0.4 Brix). Sweetness was affected only by the tastants in the base
      and not by the flavors, although flavor-specific interactions between sweetener
      type and sweetener level occurred. Flavor release from the sucrose bases was
      compared to flavor release from bases containing aspartame/acesulfame-K by static
      headspace measurements and by MS-Nose measurements using an artificial throat.
      These measurements showed greater flavor volatility from bases having low Brix
      (fewer soluble solids). This negative Brix effect was also evident in the sensory
      data for perception of some GLV green notes. The headspace data could not support
      a positive Brix effect, the typical salting out, which would correspond to the
      observed perceptual enhancement of fruity notes.

PMID- 16569061
TI  - Characterization of odor-active volatiles in apples: influence of cultivars and
      maturity stage.
AB  - The aroma and texture of three different apple cultivars, harvested at three
      maturity stages, were analyzed by sensory and instrumental analysis. The emphasis
      was on the identification of the most potent odorant volatiles, and the challenge
      was to separate the few most important flavor compounds, which may be trace
      chemicals, from the vast number of nonodorant compounds present in apple aroma
      extracts. Thirty-six odorant compounds were detected, 24 of which were common to
      all extracts. A significant correlation coefficient was found between the aroma
      intensity scores and overall quantity of the odorant volatiles, which shows that
      the development of sensory aroma is similar to that of odorant volatiles. This
      study also showed that the parameters measured by penetrometry and compression
      were highly correlated with sensory textural attributes. The determination of the
      optimal maturity stage for different apple cultivars by the usual parameters,
      such as color, diameter, total soluble solids, and titrable acidity, may not be
      sufficient to determine the optimal sensory quality for consumers. Moreover, the
      sensory quality of fruits changes during maturation in a different way from one
      cultivar to another, and this should be taken into account.

PMID- 16569062
TI  - Molecular and sensory studies on the umami taste of Japanese green tea.
AB  - Aimed at defining the key drivers for the quality-determining umami taste of a
      high-grade powdered green tea, called mat-cha, a bioactivity-guided fractionation
      using solvent extraction, solvent precipitation, preparative chromatographic
      separations, and human psychophysical experiments was applied on freshly prepared
      mat-cha. Liquid chromatography-tandem mass spectrometry and one-/two-dimensional
      nuclear magnetic resonance studies on isolated fractions led to the
      identification of l-theanine, succinic acid, 3,4,5-trihydroxybenzoic acid (gallic
      acid), and (1R,2R,3R,5S)-5-carboxy-2,3,5-trihydroxycyclohexyl-3,4,5
      trihydroxybenzoate (theogallin) as umami-enhancing compounds in the green tea
      beverage, and it can be shown by sensory studies that these compounds are able to
      raise the umami intensity of sodium l-glutamate proportionally.

PMID- 16569063
TI  - Characterization of aroma compounds of chinese "Wuliangye" and "Jiannanchun"
      liquors by aroma extract dilution analysis.
AB  - Aroma compounds in Chinese "Wuliangye" liquor were identified by gas
      chromatography-olfactometry (GC-O) after fractionation. A total of 132 odorants
      were detected by GC-O in Wuliangye liquor on DB-wax and DB-5 columns. Of these,
      126 aromas were identified by GC-mass spectrometry (MS). Aroma extract dilution
      analysis (AEDA) was further employed to identify the most important aroma
      compounds in "Wuliangye" and "Jiannanchun" liquors. The results showed that
      esters could be the most important class, especially ethyl esters. Various
      alcohols, aldehydes, acetals, alkylpyrazines, furan derivatives, lactones, and
      sulfur-containing and phenolic compounds were also found to be important. On the
      basis of flavor dilution (FD) values, the most important aroma compounds in
      Wuliangye and Jiannanchun liquors could be ethyl butanoate, ethyl pentanoate,
      ethyl hexanoate, ethyl octanoate, butyl hexanoate, ethyl 3-methylbutanoate,
      hexanoic acid, and 1,1-diethoxy-3-methylbutane (FD > or = 1024). These compounds
      contributed to fruity, floral, and apple- and pineapple-like aromas with the
      exception of hexanoic acid, which imparts a sweaty note. Several pyrazines,
      including 2,5-dimethyl-3-ethylpyrazine, 2-ethyl-6-methylpyrazine, 2,6
      dimethylpyrazine, 2,3,5-trimethylpyrazine, and 3,5-dimethyl-2-pentylpyrazine,
      were identified in these two liquors. Although further quantitative analysis is
      required, it seems that most of these pyrazine compounds had higher FD values in
      Wuliangye than in Jiannanchun liquor, thus imparting stronger nutty, baked, and
      roasted notes in Wuliangye liquor.

PMID- 16569064
TI  - Quantitative studies, taste reconstitution, and omission experiments on the key
      taste compounds in morel mushrooms (Morchella deliciosa Fr.).
AB  - Sensory-directed fractionation of an aqueous extract prepared from morel
      mushrooms led to the identification of gamma-aminobutyric acid as the chemical
      inducer of the mouth-drying and mouth-coating oral sensation imparted by morels.
      Additionally, L-glutamic acid, L-aspartic acid, succinic acid, and the previously
      unknown (S)-malic acid 1-O-beta-D-glucopyranoside, coined (S)-morelid, were
      detected as additional important umami-like taste compounds. To further bridge
      the gap between pure structural chemistry and human taste perception, 33 putative
      taste compounds were quantified in an aqueous morel extract and then rated for
      their taste contribution on the basis of dose-over-threshold factors. To confirm
      these quantitative results, an aqueous taste reconstitute was prepared by
      blending aqueous solutions of 16 amino acids, 6 organic acids, 3 purines, 4
      carbohydrates, 3 minerals, and (S)-morelid in their "natural" concentrations.
      Triangle tests revealed that the taste profile of this biomimetic organoleptic
      cocktail did not differ significantly from the taste profile of authentic morel
      extract. To finally narrow down the number of key taste compounds, taste omission
      experiments were performed demonstrating that (S)-morelid together with L
      glutamic acid, L-aspartic acid, malic acid, citric acid, acetic acid, and gamma
      aminobutyric acid are the key organoleptics of morel extract. Moreover, sensory
      experiments with model solutions showed that (S)-morelid not only imparts a sour
      and umami-like taste but is able to amplify the taste activity of monosodium
      glutamate, as well as sodium chloride, solutions.

PMID- 16569065
TI  - Comparison of physicochemical properties and starch structure of red rice and
      cultivated rice.
AB  - Sixteen red rice accessions from the southern United States were studied for
      their physical, milling, pasting, and thermal properties, chemical composition,
      and starch fine structure relative to cultivated medium- and long-grain rice
      varieties. All red rice samples were medium-grain, but their physicochemical
      properties were different from those of Bengal, a cultivated medium-grain rice.
      Their apparent amylose and crude protein contents were generally higher, and
      their amylopectin structure consisted of a higher percentage of the shorter
      branch chains (DP6-24) and a lower percentage of the longer branch chains (DP25
      65). Red rice starch pasting and thermal properties were similar to those of
      Wells, a long-grain rice cultivar. The red rice samples can be classified into
      two major clusters according to their kernel properties by hierarchical cluster
      analysis: one cluster with more resemblance to Wells and another cluster with
      more resemblance to Bengal. Starch structure and kernel physicochemical
      properties may offer an alternative way of classifying red rice in addition to
      phenotypic and genetic indices.

PMID- 16569066
TI  - Antioxidant properties of Teaw (Cratoxylum formosum Dyer) extract in soybean oil
      and emulsions.
AB  - The antioxidant activity of an extract from Teaw (Cratoxylum formosum Dyer)
      leaves was studied in soybean oil and soybean oil-in-water emulsions. Samples
      containing the extract or reference antioxidants including chlorogenic acid,
      which comprises 60% of the Teaw extract, were stored at 60 degrees C and analyzed
      periodically for peroxide value (PV) and thiobarbituric acid reactive substances
      (TBARS) to allow both hydroperoxides and hydroperoxide degradation products to be
      monitored. Chlorogenic acid and the Teaw extract were more effective than alpha
      tocopherol in inhibiting lipid oxidation in bulk oil but were less effective in
      an oil-in-water emulsion in accordance with the polar paradox. The PV/TBARS ratio
      for oil samples containing chlorogenic acid was higher than for alpha-tocopherol
      and BHT because chlorogenic acid inhibits both hydroperoxide formation by radical
      scavenging and hydroperoxide decomposition by metal chelation. The importance of
      the metal-chelating activity in retarding hydroperoxide decomposition was
      confirmed by studying the decomposition of oil samples containing added ferric
      ions. The PV/TBARS ratio was higher for citric acid than for alpha-tocopherol in
      the presence of added ferric chloride, but the order was reversed in samples
      lacking ferric chloride. Samples containing added chlorogenic acid gave the
      highest PV/TBARS ratios both in the presence and absence of ferric ions. The
      PV/TBARS ratios for the samples containing antioxidants fell rapidly to lower
      values in a soybean oil-in-water emulsion than in the soybean oil. This was due
      to increased hydroperoxide decomposition in the emulsion at the same PV. The Teaw
      extract contained 12% oil-soluble components, which contributed to a slightly
      higher oil-water partition coefficient than that of chlorogenic acid. The
      antioxidant activity of the aqueous phase of the Teaw extract was reduced more
      than that of chlorogenic acid by partitioning of the oil-soluble components into
      oil, which showed that the less-polar components contributed to the antioxidant
      activity of the Teaw extract in aqueous media.

PMID- 16569067
TI  - Comparison of the lipase activity in hydrolysis and acyl transfer reactions of
      two latex plant extracts from babaco (Vasconcellea x Heilbornii Cv.) and Plumeria
      rubra: Effect of the Aqueous microenvironment.
AB  - The enzymatic properties of Plumeria rubra latex have been evaluated for the
      first time, showing a high activity in both hydrolysis and synthesis reactions,
      and compared to the biocatalytic behavior of babaco (Vasconcellea x Heilbornii
      cv.) latex. Both biocatalysts have been optimized by studying the various
      parameters that influence reaction kinetics. The optimum temperatures for
      hydrolysis reactions were 50 and 55 degrees C for babaco and Plumeria,
      respectively. The optimum pH for babaco latex was 7, whereas for Plumeria latex,
      two optimal pH values (4 and 7) were observed. With regard to esterification and
      acyl transfer reactions such as alcoholysis and interesterification, the
      influence of thermodynamic water activity on reaction yields was determined and
      correlated with water sorption and desorption isotherms. When babaco latex is
      used as a biocatalyst, optimal synthesis reaction yields are obtained when the
      enzymatic extract is stabilized at a water activity value of 0.38, which
      corresponds to a water content of 5.7%. This optimal level of hydration is
      located on the linear portion of the biocatalyst's sorption isotherm, where the
      water molecules exhibit high-energy interactions with the protein network. In
      synthesis reactions (esterification, alcoholysis, and interesterification)
      biocatalyzed by Plumeria latex, correlation between best reaction yields and
      water activity cannot be done. Indeed, the sorption isotherm plot has an atypical
      shape, indicating that water might be trapped in the latex matrix and,
      consequently, that the water content of the biocatalyst is highly dependent on
      the hydration history of the latex.

PMID- 16569068
TI  - Proteome analysis of the sarcoplasmic fraction of pig semimembranosus muscle:
      implications on meat color development.
AB  - Two-dimensional electrophoresis was used to investigate sarcoplasmic protein
      expression in pig Semimembranosus muscles sampled 20 min after slaughter. Two
      groups (light and dark) of 12 animals were selected from 1000 pigs, based on meat
      L values measured 36 h postmortem. Twenty-two proteins or fragments (p < 0.05)
      were differentially expressed. Muscles leading to darker meat had a more
      oxidative metabolism, indicated by more abundant mitochondrial enzymes of the
      respiratory chain, hemoglobin, and chaperone or regulator proteins (HSP27, alphaB
      crystallin, and glucose-regulated protein 58 kDa). Conversely, enzymes of
      glycolysis were overexpressed in the lighter group. Such samples were also
      characterized by higher levels of glutathione S-transferase omega, which can
      activate the RyR calcium channels, and higher levels of cyclophilin D. This
      protein pattern is likely to have severe implications on postmortem metabolism,
      namely, acceleration of ATP depletion and pH fall and subsequent enhanced protein
      denaturation, well-known to induce discoloration.

PMID- 16569069
TI  - Yellow passion fruit rind--a potential source of low-methoxyl pectin.
AB  - Yellow passion fruit (Passiflora edulis f. flavicarpa Degener) rind pectic
      substances were fractionated with water, ammonium oxalate, and dilute acid
      solutions. The extracted pectins were rich in anhydrogalacturonic acid and had a
      low degree of methyl esterification. Moreover, their acetyl groups and neutral
      sugar contents were relatively low. Furthermore, a low amount of proteinaceous
      material was also found within them. Their gelling ability and viscoelastic
      properties as evaluated by the SAG and small amplitude oscillatory shear tests,
      respectively, were comparable to those of a commercial citrus low-methoxyl
      pectin. Hence, yellow passion fruit rind occurs as a potentially good source of
      naturally low-methoxyl pectin.

PMID- 16569070
TI  - Changes in membrane fatty acids composition of microbial cells induced by
      addiction of thymol, carvacrol, limonene, cinnamaldehyde, and eugenol in the
      growing media.
AB  - Major active compounds from essential oils are well-known to possess
      antimicrobial activity against both pathogen and spoilage microorganisms. The aim
      of this work was to determine the alteration of the membrane fatty acid profile
      as an adaptive mechanism of the cells in the presence of a sublethal
      concentration of antimicrobial compound in response to a stress condition.
      Methanolic solutions of thymol, carvacrol, limonene, cinnamaldehyde, and eugenol
      were added into growth media of Escherichia coli O157:H7, Salmonella enterica
      serovar typhimurium, Pseudomonas fluorescens, Brochothrix thermosphacta, and
      Staphylococcus aureus strains. Fatty acid extraction and gas chromatographic
      analysis were performed to assess changes in membrane fatty acid composition.
      Substantial changes were observed on the long chain unsaturated fatty acids when
      the E. coli and Salmonella strains grew in the presence of limonene and
      cinnamaldehyde and carvacrol and eugenol, respectively. All compounds influenced
      the fatty acid profile of B. thermosphacta, while Pseudomonas and S. aureus
      strains did not show substantial changes in their fatty acid compositions.

PMID- 16569071
TI  - Comparison of methods for the exhaustive extraction of hypericins, flavonoids,
      and hyperforin from Hypericum perforatum L.
AB  - Renewed interest in plant-derived drugs has led to an increased need for
      efficient extraction methods. Hypericum perforatum L. contains several groups of
      bioactive compounds with noteworthy pharmacological activities. Direct sonication
      of H. perforatum was investigated and compared with conventional maceration,
      indirect sonication, Soxhlet extraction, and accelerated solvent extraction
      (ASE). Highly selective liquid chromatography/tandem mass spectrometry analysis
      showed that the content of six investigated active compounds (hypericin,
      pseudohypericin, hyperoside, rutin, quercitrin, and hyperforin) in extracts
      obtained by direct sonication was significantly higher than in extracts obtained
      by the other methods. The active compound contents increased on increasing the
      ultrasonic power from 40 to 60 W when using direct sonication. Conventional
      maceration gave the lowest amount of analyzed active compounds. Soxhlet
      extraction gave better results than ASE or indirect sonication.

PMID- 16569072
TI  - Isolation and identification of select oligosaccharides from commercially
      produced total invert sugar with a proposed mechanism for their formation.
AB  - Three disaccharides were isolated and purified from a commercial total invert
      sugar (TIS). The structures of these compounds were determined by a combination
      of acid and enzymatic hydrolysis studies, chromatographic comparison to
      standards, and nuclear magnetic resonance spectroscopy. These carbohydrates were
      identified as O-alpha-D-glucopyranosyl-(1-->3)-D-fructose (IS1), O-beta-D
      fructofuranosyl-(2-->6)-D-glucose (IS2), and O-alpha-D-glucopyranosyl-beta-D
      glucopyranoside (IS3). On the basis of these structures a mechanism for the
      hydrochloric acid catalyzed hydrolysis of sucrose is proposed: protonation of the
      glycosidic oxygen of sucrose leading to the formation of glucopyranosyl and
      fructofuranosyl oxonium ions of D-glucose or D-fructose, respectively, followed
      by nucleophilic attack of these ions by D-glucose or D-fructose at either the
      alpha- or beta-face.

PMID- 16569073
TI  - Formation of dityrosine cross-links during breadmaking.
AB  - To establish its significance during commercial breadmaking, dityrosine formation
      was quantified in flours and doughs of six commercial wheat types at various
      stages of the Chorleywood Bread Process. Dityrosine was formed mainly during
      mixing and baking, at the levels of nmol/g dry weight. Good breadmaking flours
      tended to exhibit a higher dityrosine content in the final bread than low quality
      ones, but no relationship was found for dityrosine as a proportion of flour
      protein content, indicating that the latter was still a dominant factor in the
      analysis. There was no correlation between gluten yield of the six wheat types
      and their typical dityrosine concentrations, suggesting that dityrosine cross
      links were not a determinant factor for gluten formation. Ascorbic acid was found
      to inhibit dityrosine formation during mixing and proving, and it has no
      significant effect on dityrosine in the final bread. Hydrogen peroxide promoted
      dityrosine formation, which suggests that a radical mechanism involving
      endogenous peroxidases might be responsible for dityrosine formation during
      breadmaking.

PMID- 16569074
TI  - Chemical and biological assessment of a chinese herbal decoction containing Radix
      Astragali and Radix Angelicae Sinensis: Determination of drug ratio in having
      optimized properties.
AB  - Danggui Buxue Tang (DBT), a Chinese medicinal decoction that is commonly used as
      a dietary supplement in treating woman with menopausal irregularity, contains two
      herbs: Radix Astragali (Huangqi) and Radix Angelicae Sinensis (Danggui). The
      ratio of Radix Astragali and Radix Angelicae Sinensis used in DBT should be 5:1
      as described in China in 1247 A.D.; however, the rationale of this formula has
      not been given. Here, the chemical and biological properties of DBT, prepared
      from different ratios of the drugs, were determined. Significantly, higher
      amounts of Radix Astragali-derived astragaloside IV, calycosin, and formononetin
      and Radix Angelicae Sinensis-derived ferulic acid were found in DBT with Radix
      Astragali and Radix Angelicae Sinensis in a 5:1 ratio. By using the biological
      effects of DBT in stimulating osteoblast proliferation, estrogen promoter
      activation, and anti-platelet aggregation activity, the drug ratio of 5:1
      produced the best effects. In addition, the use of ethanol-treated Radix
      Angelicae Sinensis enhanced the efficacy of DBT, and the treatment further
      increased the solubilities of chemical constituents. By analyzing the correlation
      of chemical and biological results, several chemicals showed positive correlation
      with DBT-induced bioactivities. The current results support the ancient
      formulation of DBT, and the identified chemicals could serve as markers for
      quality control of DBT.

PMID- 16569075
TI  - Octenyl succinic anhydride modified early indica rice starches differing in
      amylose content.
AB  - Seven early indica rice starches with different amylose contents were modified by
      octenyl succinic anhydride (OSA) in aqueous suspension systems to evaluate the
      effect of amylose contents on starch esterification. The crystalline structure
      and pasting properties of starches were investigated using X-ray diffraction and
      a Rapid Visco Analyzer (RVA). The results indicated that the amylose content had
      a positive impact on the OSA modification. As the amylose content increased from
      0 to 39.6%, the degree of substitution increased from 0.024 to 0.030 and the
      reaction efficiency increased from 62.8 to 77.5%. X-ray diffraction scans
      confirmed that the amylose was mainly present in the amorphous domain of the
      granule and was highly substituted after the OSA treatment. The RVA profiles
      demonstrated that the OSA starches had higher viscosities than their native
      counterparts. Moreover, negative correlations were observed between the amylose
      content and the major RVA parameters (e.g., peak viscosity, hot paste viscosity,
      cool paste viscosity, and breakdown viscosity).

PMID- 16569076
TI  - Digestive Stability, micellarization, and uptake of beta-carotene isomers by Caco
      2 human intestinal cells.
AB  - While isomeric profiles of carotenoids found in food often differ from those in
      body fluids and tissues, insights about the basis for these differences remain
      limited. We investigated the digestive stability, relative efficiency of
      micellarization, and cellular accumulation of trans and cis isomers of beta
      carotene (BC) using an in vitro digestion procedure coupled with human intestinal
      (Caco-2) cells. A meal containing applesauce, corn oil, and either water-soluble
      beadlets (WSB) or Dunaliella salina (DS) as a BC source was subjected to
      simulated gastric and small intestinal digestion. BC isomers were stable during
      digestion, and the efficiency of micellarization of cis-BC isomers exceeded that
      of all-trans-BC isomers. The cellular profile of carotenoids generally reflected
      that in micelles generated during digestion, and intracellular isomerization was
      minimal. These data suggest that cis isomers of BC are preferentially
      micellarized during digestion and transferred across the brush-border surface of
      the enterocyte from mixed micelles with similar efficiency as all-trans-BC at the
      concentrations of the carotenoids utilized in this study.

PMID- 16569077
TI  - Quantitation of furan and methylfuran formed in different precursor systems by
      proton transfer reaction mass spectrometry.
AB  - Furan has recently received attention as a possibly hazardous compound occurring
      in certain thermally processed foods. Previous model studies have revealed three
      main precursor systems producing furan upon thermal treatment, i.e., ascorbic
      acid, Maillard precursors, and polyunsaturated lipids. We employed proton
      transfer reaction mass spectrometry (PTR-MS) as an on-line monitoring technique
      to study furan formation. Unambiguous identification and quantitation in the
      headspace was achieved by PTR-MS/gas chromatography-mass spectrometry coupling.
      Ascorbic acid showed the highest potential to generate furan, followed by
      glyceryl trilinolenate. Some of the reaction samples generated methylfuran as
      well, such as Maillard systems containing alanine and threonine as well as lipids
      based on linolenic acid. The furan yields from ascorbic acid were lowered in an
      oxygen-free atmosphere (30%) or in the presence of reducing agents (e.g.,
      sulfite, 60%), indicating the important role of oxidation steps in the furan
      formation pathway. Furthermore, already simple binary mixtures of ascorbic acid
      and amino acids, sugars, or lipids reduced furan by 50-95%. These data suggest
      that more complex reaction systems result in much lower furan amounts as compared
      to the individual precursors, most likely due to competing reaction pathways.

PMID- 16569078
TI  - Identification of steviol glucuronide in human urine.
AB  - Stevioside (250 mg capsules) was given three times daily to 10 healthy subjects.
      Steviol glucuronide (steviol 19-O-beta-D-glucopyranosiduronic acid; MM, 494.58;
      melting point, 198-199 degrees C) was characterized in the 24 h urine as the only
      excretion product of oral stevioside by MS, NMR, IR, and UV spectroscopy. This is
      the first report on the unambiguous identification of steviol glucuronide in
      human urine.

PMID- 16569079
TI  - Safety of drug therapies used for weight loss and treatment of obesity.
AB  - Some of the medications used for weight loss in the management of obesity have
      been associated with unacceptable morbidity and mortality. Safety concerns have
      led to the withdrawal of aminorex, followed by the fenfluramines in 1997, and
      phenylpropanolamine (norephedrine) in 2000. Aminorex was associated with an
      increased prevalence of primary pulmonary hypertension (PPH), fenfluramines with
      an increased prevalence of PPH and valvulopathy, and phenylpropanolamine with an
      increased risk of haemorrhagic stroke. Several studies have investigated the
      safety of the fenfluramines, yet the benefit-risk profile has not been
      conclusively quantified. This is due to several deficiencies in the published
      studies, including a lack of data on the baseline prevalences of comorbid
      conditions in obese subjects, and potential confounders and biases in the study
      designs. Although several studies and systematic reviews support an increased
      risk of PPH and valvulopathy in patients who have taken fenfluramines, without
      knowledge of the background prevalence it is not possible to determine if the
      exposure preceded the outcome. The population at higher risk of these adverse
      effects includes those taking higher doses or with a longer duration of exposure
      to fenfluramines and those with pre-existing cardiac disease or a genetic
      predisposition. Patients exposed to fenfluramines continue to be monitored, with
      some follow-up studies indicating no overall worsening in valvulopathy over time.
      There are limited efficacy and safety data for amfepramone (diethylpropion) and
      phentermine and their approval for the management of obesity is limited to short
      term use. Orlistat and sibutramine are the only currently approved medications
      for long-term management of obesity. Although the benefit-risk profiles of
      sibutramine and orlistat appear positive, sibutramine continues to be monitored
      because of long-term safety concerns. The safety and efficacy of currently
      approved drug therapies have not been evaluated in children and elderly patient
      populations and there is limited information in adolescents, whilst the long-term
      safety of current and potential new drug therapies in adults will require several
      years of postmarketing surveillance to fully elucidate their adverse effect
      profiles.

PMID- 16569080
TI  - Long-term treatment with atypical antipsychotics and the risk of weight gain : a
      literature analysis.
AB  - The aim of this review is to analyse and summarise the literature data about the
      incidence of weight gain in patients exposed to atypical antipsychotics during
      long-term (>or=1 year) treatment regimens. Despite the clinical relevance of the
      topic, the vast majority of reviewed studies showed methodological limitations.
      Some trials had retrospective analysis, and concomitant medications also
      associated with an increased risk of weight gain, such as antidepressants and
      mood stabilisers, were often prescribed. Results were obtained from clinical
      trials conducted using flexible dosages; thus, the relationship between dosage
      and weight change was not explored adequately. Also, in a large number of
      studies, the average antipsychotic daily dose was lower than the usual dosage in
      clinical practice. Moreover, weight gain was evaluated by different measures,
      such as mean weight gain in the enrolled population, percentage of patients who
      gained >7% of basal weight or body mass index (BMI) variations from baseline. In
      short-term studies, a definite rank order of weight-gain potential among atypical
      antipsychotics has been demonstrated: clozapine is related to the highest risk of
      weight gain, followed in decreasing order of magnitude by olanzapine, quetiapine,
      risperidone, amisulpride, aripiprazole and ziprasidone. However, in long-term
      studies, except for clozapine at one end of the scale and ziprasidone at the
      other, the differences in weight-gain liability showed by the other atypical
      antipsychotics became less intense. Differences between short-term and long-term
      treatment could be due to a complex overlapping of different factors, both drug
      specific (relative receptorial affinity; timing of weight change plateau; and
      drug-specific/dose-dependent weight gain), and patient-specific (genetic
      vulnerability; sex; age; BMI; weight before starting antipsychotic treatment;
      type of psychiatric disorder; and individual lifestyle). There is an urgent need
      for well designed, randomised controlled trials to assess firmly both the
      differential effects of atypical antipsychotics on weight and the role of other
      factors in contributing to iatrogenic unwanted weight changes. Meanwhile, the
      well known benefits shown by some atypical antipsychotics in reducing akathisia
      and other extrapyramidal adverse effects and improving cognition should be
      carefully balanced with the problems of weight gain, other metabolic
      complications and higher health care costs.

PMID- 16569081
TI  - Thalidomide use in the US : experience with pregnancy testing in the S.T.E.P.S.
      programme.
AB  - INTRODUCTION: In 1998, thalidomide (Thalomid), a known human teratogen, was
      approved by the US FDA for the treatment of erythema nodosum leprosum. To prevent
      fetal exposure to thalidomide, a restricted distribution risk management
      programme, the System for Thalidomide Education and Prescribing Safety
      (S.T.E.P.S.), was implemented. All clinicians, pharmacists and patients who
      prescribe, dispense and receive thalidomide, respectively, are required to enroll
      in S.T.E.P.S. Sexually active females of childbearing potential must use two
      methods of birth control before, during and after treatment. These patients must
      also have a negative pregnancy test within 24 hours before beginning therapy and
      periodically while on therapy. The objective of this report is to summarise the
      patterns of thalidomide use and to describe the occurrence of positive pregnancy
      tests in females of childbearing potential while they were using thalidomide in
      the S.T.E.P.S. programme in the US. STUDY DESIGN/METHODS: A retrospective review
      of patients receiving thalidomide within the S.T.E.P.S. programme from September
      1998 to 31 December 2004 to determine the occurrence of positive pregnancy tests
      whilst on treatment. RESULTS: Approximately 124,000 (43% female) patients were
      registered within the S.T.E.P.S. programme between September 1998 and 31 December
      2004. Approximately 6,000 patients were females of childbearing potential,
      representing 5% of all patients and 11% of all female patients. Between 30 July
      2001 and 31 December 2004, >88% of thalidomide use was for oncological
      conditions. There were 72 females of childbearing potential who had positive
      pregnancy tests. Sixty-nine of these patients had false positive pregnancy tests.
      Of the remaining three, one woman was pregnant while on thalidomide. This patient
      had an initial negative test and received thalidomide. Therapy was stopped when
      she had a positive pregnancy test. This pregnancy resulted in a miscarriage. Two
      additional patients were determined to be pregnant before receiving thalidomide.
      CONCLUSIONS: The S.T.E.P.S. programme is critical to managing the risks of
      thalidomide-associated teratogenicity. Sustained vigilance among health care
      providers and patients receiving thalidomide is essential to its continued
      success. Health care providers should be aware of the occurrence of false
      positive pregnancy tests in females of childbearing potential receiving
      thalidomide.

PMID- 16569082
TI  - Influence of pharmacists' attitudes on adverse drug reaction reporting : a case
      control study in Portugal.
AB  - INTRODUCTION: Pharmacists can play a fundamental role in adverse drug reaction
      (ADR) reporting, although the factors that affect underreporting among these
      professionals are unknown. The objectives of this study were to identify (i)
      professional or demographic characteristics; and (ii) attitudes associated with
      pharmacists' ADR reporting in northern Portugal. METHODS: We conducted a case
      control study on a population of pharmacists employed in hospital and community
      pharmacies across Portugal's Northern Regional Health Authority catchment area in
      2003. Cases (n=34) comprised pharmacists who had reported at least one ADR to the
      northern region's drug surveillance unit, and controls (n=280) were randomly
      sampled from pharmacists who had never reported an ADR. All were interviewed
      using a mail questionnaire. Most attitudes were based on Inman's 'seven deadly
      sins' and were measured using a continuous visual analogue scale. Answers were
      recorded in a range from 0 (total disagreement) to 10 (total agreement). Logistic
      regression was used to determine the ADR reporting adjusted odds ratio (OR) for a
      change in exposure corresponding to the interquartile range for each attitude.
      RESULTS: The response rate was 86.8%. Reporting probability proved higher among
      hospital versus community pharmacists (adjusted OR 20.0; 95 CI 3.3, 125.0;
      p<0.001). Attitudes to ADRs were strongly associated with reporting probability.
      Hence, an interquartile decrease in any of the following attitudes increased the
      probability of reporting by (i) 223% (95% CI 51, 595; p < 0.05) for "Really
      serious ADRs are well documented by the time a drug is marketed"; (ii) 240% (95%
      CI 89, 508; p=0.002) for "I would only report an ADR if I were sure that it was
      related to the use of a particular drug"; (iii) 316% (95% CI 44, 1104; p=0.010)
      for "It is only necessary to report serious or unexpected ADRs"; and (iv) 171%
      (95% CI 13, 549; p=0.020) for "I do not have time to think about the involvement
      of the drug or other causes in ADRs". CONCLUSIONS: ADR under-reporting is
      strongly associated with certain attitudes, possibly indicating that under
      reporting could be minimised through educational interventions targeted at
      changing such attitudes. Pharmacists' ADR education must be improved and
      educational programmes should be focused on altering attitudes identified by the
      study as being associated with under-reporting. Our data also indicate that
      community pharmacists must be a priority target for this intervention.

PMID- 16569084
TI  - The strong African American families program: prevention of youths' high-risk
      behavior and a test of a model of change.
AB  - In this study, the efficacy of the Strong African American Families Program
      (SAAF) was tested. The trial, which included 332 families, indicated that
      families who participated in SAAF experienced increases over time in regulated,
      communicative parenting; increases in targeted parenting behaviors, according to
      youths' reports; and low rates of high-risk behavior initiation among youths.
      Changes in regulated, communicative parenting mediated the intervention's impact
      on youths' recognition of changes in parenting, which in turn was linked to
      changes in youths' high-risk behavior.

PMID- 16569085
TI  - The context of aggressive behavior in marriage: a longitudinal study of
      newlyweds.
AB  - Under what circumstances are spouses more or less likely to engage in aggressive
      behaviors? To address this question, the current study drew on multiple
      longitudinal assessments of 1st-married newlyweds to examine correlates of within
      subject variability in aggressive behavior. Controlling for marital satisfaction,
      the authors found that spouses were more likely to engage in physical aggression
      at times when they engaged in higher levels of psychological aggression.
      Additionally, husbands reporting higher levels of chronic stress were more likely
      to engage in physical aggression overall and were more likely to engage in
      physical aggression when they were experiencing higher than average levels of
      acute stress. These results highlight how demands and supports in the context
      external to a marriage may affect processes within the marriage.

PMID- 16569086
TI  - The role of family relationship quality and testosterone levels in adolescents'
      peer experiences: a biosocial analysis.
AB  - Grounded in a biosocial model, this study examines the interaction between
      adolescents' testosterone levels and qualities of the parent-adolescent and
      sibling-adolescent relationship in adolescents' peer experiences and contributes
      to empirical research on the role of biological factors and family socialization
      processes in adolescents' peer competence and involvement. Participants included
      331 adolescents (M = 14.68 years of age, SD = 1.53) and their mothers and fathers
      in 173 families. During home visits, data were collected from family members
      regarding adolescents' family relationships, peer relationships, and psychosocial
      adjustment; daily time-use data were gathered during a series of 7 nightly phone
      interviews; and testosterone levels were assessed through saliva samples.
      Hierarchical regression results revealed that when boys had close relationships
      with mothers and sisters, testosterone was positively associated with their peer
      competence and involvement. Discussion focuses on the value of exploring
      biosocial interactions and highlights the particular importance of boys'
      relationships with opposite-sex family members in efforts to understand their
      peer experiences.

PMID- 16569087
TI  - Longitudinal relations between marital conflict and child adjustment: vagal
      regulation as a protective factor.
AB  - Although associations between marital conflict and children's adjustment problems
      are established, less is known about child individual differences that can have
      an impact on these relations. The authors examined longitudinal relations between
      marital conflict and children's adjustment using a community sample of elementary
      school-age children and young adolescents and assessed the role of children's
      vagal regulation in moderating the conflict-child problems link. Elevated marital
      conflict was predictive of negative child outcomes, and greater vagal suppression
      to a simulated argument was protective against internalizing problems associated
      with marital conflict. Findings are supportive of the value of a biopsychosocial
      perspective and illustrate that child vagal regulation can contribute to the
      aggregation or amelioration of risk for maladjustment in the context of exposure
      to marital conflict.

PMID- 16569088
TI  - Moderators of the association between relationship discord and major depression
      in a national population-based sample.
AB  - Although there is a well-documented association between relationship discord and
      depression, many individuals experience either discord or depression without
      experiencing the other. To understand this phenomenon, the authors evaluated
      moderators of the association between relationship discord and major depression
      among married or cohabiting individuals in the National Comorbidity Survey (N =
      2,538; R. C. Kessler et al., 1994). Potential moderators included demographics,
      personality characteristics, parental depression, and childhood loss. Only one
      significant moderator was found: There was a stronger association between discord
      and depression for married people (vs. cohabiters). Among married individuals
      only, neuroticism also served as a moderator: Individuals higher in neuroticism
      showed a stronger association between discord and depression. In general,
      findings suggest that when a person or family presents with one problem (e.g.,
      relationship discord), it is important to evaluate and potentially treat the
      other problem (e.g., depression) as well.

PMID- 16569089
TI  - Bringing work home: the emotional experiences of mothers and fathers.
AB  - Given the salience of work in our society, this study investigated how intrinsic
      work motivation, work hours, and taking time for self influenced the interplay
      between the emotional climates of work and home. The authors examined day-to-day
      emotional transmission between work and home (spillover) for 143 families using
      the experience sampling method and interview data from the Sloan Center's 500
      Family Study (L. J. Waite & B. Schneider, 1997). Intrinsic work motivation, work
      hours, and taking time for self were used as predictors of spillover. There was
      evidence of emotional transmission from work to home for mothers' happiness,
      anger, and anxiety as well as for father's anxiety. Also, fathers scoring higher
      on intrinsic work motivation tended to report greater overall anxiety at home
      after the workday. Anxiety from work was less likely to spill over to the home
      when fathers reported working longer hours. These findings have practice
      implications for improving worker productivity and the well-being of two-working
      parent families.

PMID- 16569090
TI  - Domestic violence, emotion coaching, and child adjustment.
AB  - This article addresses the question of whether parents in domestically violent
      homes have difficulty talking to and helping their children manage their emotions
      what has been referred to as emotion coaching. Emotion coaching as a moderator in
      the relationship between domestic violence (DV) and children's behavior problems
      was also examined. Results indicated that DV was not associated with a general
      deficit in emotion coaching but that DV was associated with less coaching of
      anger and fear depending on whether the parent was the perpetrator or victim of
      DV. Emotion coaching also moderated the relationship between DV and children's
      behavior problems. Implications for the development of an intervention program to
      improve parental coaching of emotion in domestically violent homes is discussed.

PMID- 16569091
TI  - Authoritarian parenting in individualist and collectivist groups: Associations
      with maternal emotion and cognition and children's self-esteem.
AB  - Mothers and children between the ages of 7 and 12, from individualist (Western
      European) and collectivist (Egyptian, Iranian, Indian, and Pakistani)
      backgrounds, completed assessments of children's self-esteem, maternal
      authoritarianism, and mothers' thoughts and feelings about their children.
      Collectivist mothers endorsed authoritarian parenting more than did individualist
      mothers but did not feel or think more negatively about their children, and
      collectivist children were not lower in self-esteem. Within both groups, maternal
      negative affect and cognition were associated with lower self-esteem in children.
      However, maternal authoritarianism was associated with maternal negative emotion
      and cognition only in the individualist group. The results suggest that maternal
      negative thoughts and feelings, associated with authoritarianism in individualist
      but not collectivist groups, may be more detrimental to children's self-esteem
      than is authoritarianism in and of itself.

PMID- 16569092
TI  - Impact of racial perspectives and contextual variables on marital trust and
      adjustment for African American couples.
AB  - This study examined the associations of racial perspectives that represent pro
      African American, anti-African American, or a mixture of these beliefs with
      marital trust and adjustment for African American couples (N = 93). Religious
      well-being and socioeconomic status (SES) were examined as contextual moderators.
      For husbands only, the anti-African American perspective was inversely associated
      with couple functioning, the mixed perspective was inversely associated with
      marital trust, and the pro-African American perspective predicted marital trust
      only for husbands having relatively low religious well-being and relatively high
      SES. The limited effects of pro-African American attitudes suggest the need to
      evaluate a wider range of these attitudes in future research. Also, findings
      corroborate suggestions for therapists to routinely assess and address both
      cultural pride and shame issues relevant to African American couple
      relationships.

PMID- 16569093
TI  - Young children's appraisals of interparental conflict: Measurement and links with
      adjustment problems.
AB  - The present study investigated 2 questions pertinent to understanding
      developmental aspects of children's conflict appraisals: (a) Do 7- to 9-year-old
      children make reliable distinctions between their perceptions of conflict and
      their appraisals of threat and self-blame? (b) Do threat and blame appraisals
      mediate the association between exposure to interparental conflict and adjustment
      problems in this age group? Factor analysis of a new version of the Children's
      Perception of Interparental Conflict Scale (CPIC-Y) designed for younger children
      showed that 179 7- to 9-year-old children distinguished properties of conflict
      from their appraisals of it. Moreover, as predicted by the cognitive-contextual
      framework, threat and self-blame appraisals mediated the link between conflict
      and internalizing problems but not externalizing problems. This study provides
      compelling evidence that appraisals of interparental conflict can be reliably
      measured at relatively young ages and suggests that perceptions of threat and
      self-blame function similarly in 7- to 9-year-olds as they do in older children.

PMID- 16569094
TI  - Maternal resolution of child diagnosis: stability and relations with child
      attachment across the toddler to preschooler transition.
AB  - In this longitudinal study, the authors investigated individual differences in
      how families adapt to a child's congenital disorder. Family impact, maternal
      grief resolution, and child attachment were assessed among 74 mothers and their
      toddlers with a neurological disorder or disfigurement. Fifty dyads were
      reevaluated 16 months later. For children with neurological compared with
      disfigurement diagnoses, there was a greater likelihood of negative impact on
      family, unresolved maternal grief, and insecure attachment at Time 1. Children
      classified as secure were significantly more likely to have mothers classified as
      resolved regarding their reactions to their children's diagnosis. Maternal grief
      resolution was significantly stable (77%) over time and mediated the relation
      between type of diagnosis and child security. With time, negative impact of child
      condition on the family decreased and percentage of children classified as secure
      increased, suggesting that on average families improved. Results suggest that
      helping parents come to terms emotionally and cognitively with their child's
      condition may be a useful focus for intervention.

PMID- 16569095
TI  - Adolescent and parent therapeutic alliances as predictors of dropout in
      multidimensional family therapy.
AB  - The authors examined the relations between adolescent-therapist and mother
      therapist therapeutic alliances and dropout in multidimensional family therapy
      for adolescents who abuse drugs. The authors rated videotapes of family therapy
      sessions using observational methods to identify therapist-adolescent and
      therapist-mother alliances in the first 2 therapy sessions. Differences in
      adolescent and mother alliances in families that dropped out of therapy and
      families that completed therapy were compared. Results indicate that both
      adolescent and mother alliances with the therapist discriminated between dropout
      and completer families. Although no differences were observed between the 2
      groups in Session 1, adolescents and mothers in the dropout group demonstrated
      statistically significantly lower alliance scores in Session 2 than adolescents
      and parents in the completer group. These findings are consistent with other
      research that has established a relationship between therapeutic alliance and
      treatment response.

PMID- 16569096
TI  - Premarital education, marital quality, and marital stability: findings from a
      large, random household survey.
AB  - One of the limitations of experimental studies on the effectiveness of premarital
      education is the reliance on samples of mostly White, middle-class couples. In
      contrast, although survey methods allow only weak inferences about causal
      relations, representative surveys can yield important information about use and
      estimated effects across a diverse population. Using a large random survey of 4
      middle American states, the authors found that participation in premarital
      education was associated with higher levels of satisfaction and commitment in
      marriage and lower levels of conflict-and also reduced odds of divorce. These
      estimated effects were robust across race, income (including among the poor), and
      education levels, which suggests that participation in premarital education is
      generally beneficial for a wide range of couples.

PMID- 16569097
TI  - Reducing conduct problems among children brought to women's shelters:
      intervention effects 24 months following termination of services.
AB  - This study evaluated the long-term effects of Project SUPPORT, an intervention
      designed to reduce conduct problems among children in domestically violent
      families. Participating mothers had sought shelter because of domestic violence
      and had at least one child (4-9 years old) exhibiting clinical levels of conduct
      problems. Results indicated that at 2 years posttreatment, 15% of children in
      families in the Project SUPPORT condition exhibited clinical levels of conduct
      problems compared with 53% of those in the existing services condition. In
      addition, mothers of children in the Project SUPPORT condition reported their
      children to be happier, to have better social relationships, and to have lower
      levels of internalizing problems, relative to children in the comparison
      condition. Mothers in the Project SUPPORT condition were less likely to use
      aggressive child management strategies and were less likely to have returned to
      their partners during the follow-up period.

PMID- 16569098
TI  - Estimating the number of American children living in partner-violent families.
AB  - The number of American children living in partner-violent households was
      estimated from a nationally representative sample of 1,615 dual-parent
      households. Approximately 15.5 million American children were estimated to live
      in families in which partner violence had occurred at least once in the previous
      year, with 7 million estimated to live in families in which severe partner
      violence had occurred. The prevalence of partner violence was higher among
      couples with children than among couples without children.

PMID- 16569099
TI  - Parent-child relationships as systems of support or risk for adolescent
      suicidality.
AB  - This study examined a process model of predicting adolescent suicidality.
      Adolescent emotional distress was hypothesized to mediate the relationship
      between parental behaviors and subsequent adolescent suicidality. The parental
      behaviors studied included parental warmth and parental hostility. A sample of
      451 families from rural Iowa participated in this longitudinal study, which
      included both observational and self-report data. Models were tested with
      structural equation modeling. Adolescent emotional distress was found to be a
      mediating variable between paternal warmth and adolescent suicidality. Results
      indicated that maternal warmth predicted adolescent suicidality but not emotional
      distress. Parental hostility did not predict either latent variable. Clinical
      implications are provided.

PMID- 16569100
TI  - Predicting marital distress and dissolution: refining the two-factor hypothesis.
AB  - Measures of communication, hostility, and neuroticism taken from 85 couples from
      Germany before marriage were used to predict marital outcomes 5 years later.
      Hostility and neuroticism discriminated between couples who separated or divorced
      after 5 years and those who remained married, whereas communication discriminated
      between married-satisfied and married- dissatisfied couples. Only hostility and
      neuroticism predicted marital satisfaction at 18 months, suggesting that these
      factors contribute to rapid, early declines in marital functioning. The authors
      conclude that poor communication alone cannot account for the full range of
      marital outcomes and that skill-based models of marriage can be strengthened by
      considering relatively rare exchanges between partners (e.g., aggression) and
      their enduring vulnerabilities (e.g., neuroticism).

PMID- 16569101
TI  - Do couples at high risk of relationship problems attend premarriage education?
AB  - The effectiveness of premarriage education is limited by whether couples at high
      risk of future marital problems attend such education. In the current study, 374
      newly married couples were assessed on a range of risk factors for future marital
      problems as well as whether they had attended marriage education. Couples with
      certain indices of relationship risk (nonreligious and premarital cohabitation)
      were underrepresented in premarriage education. Suggestions are offered to
      attract more couples, particularly those at high risk for future problems, to
      relationship education.

PMID- 16569102
TI  - Longitudinal association between marital dissatisfaction and alcohol use
      disorders in a community sample.
AB  - The prospective association between marital dissatisfaction and alcohol use
      disorders (abuse and/or dependence) was evaluated in a randomly selected
      community sample. Married individuals (N = 1,675) from the New Haven
      Epidemiologic Catchment Area project who did not have a current alcohol use
      disorder at baseline were followed prospectively for 12 months. Results indicated
      that baseline marital dissatisfaction was significantly associated with alcohol
      use disorder diagnosis during follow-up, with dissatisfied spouses being 3.7
      times more likely than satisfied spouses to have a diagnosis of current alcohol
      use disorder at follow-up. The longitudinal association between baseline marital
      dissatisfaction and current alcohol use disorder diagnosis at follow-up remained
      significant when controlling for baseline demographic variables and history of
      alcohol use disorders.

PMID- 16569103
TI  - Application of ecological momentary assessment to the study of marital adjustment
      and social interactions during daily life.
AB  - The authors examined the utility of ecological momentary assessment for assessing
      spousal interactions in the natural environment among 245 healthy, married, older
      adults. Convergent validity for this method was demonstrated by (a) a positive
      association between marital adjustment (MA) and average diary ratings of
      agreeableness during spousal interactions and (b) an inverse association between
      MA and average diary ratings of conflict during spousal interactions. When
      agreeableness and conflict were examined simultaneously for spousal interactions,
      only agreeableness independently predicted MA. By contrast, when nonspousal
      interactions were examined, only conflict during nonspousal interactions was an
      independent predictor of MA. Results underscore the merit of obtaining
      representative measures of social interactions during daily life for
      understanding influences on and consequences of MA.

PMID- 16569104
TI  - Dispositional optimism as a predictor of men's decision-related distress after
      localized prostate cancer.
AB  - This study investigated prospectively the relationship between optimism, threat
      appraisal, seeking support and information, cognitive avoidance, physical
      treatment side effects, and decision-related distress in 111 men with localized
      prostate cancer. Men were assessed at diagnosis and 2 and 12 months after
      treatment. Baseline decision-related distress predicted distress 2 and 12 months
      after treatment. Optimism was a significant prospective and concurrent predictor
      of decision-related distress, with the effect mediated by proximal cancer threat
      appraisal. Seeking support and information and cognitive avoidance were not
      associated with decision-related distress at any time point. For physical
      treatment side effects, concurrent urinary symptoms were predictive of decision
      related distress 2 months after treatment. Results suggest that decision-related
      distress is generated by similar processes to that of the psychological distress
      that follows a cancer diagnosis. Screening for men with high decision-related
      distress for referral to in-depth decision support is suggested. Outcome
      expectations may present as a therapy target to increase the effectiveness of
      decisional support that is utility based.

PMID- 16569105
TI  - Why worry? Worry, risk perceptions, and willingness to act to reduce medical
      errors.
AB  - Through the domain of medical errors, the role of worry and perceived risk in
      precautionary behaviors was examined in a convenience sample (N = 195, mean age =
      42 years, 71% female). Worry was linked to fatality estimates. A model of the
      antecedents and consequences of worry also was tested. Risk characteristics such
      as dread and preventability, negative reactivity, and vulnerability to medical
      errors appeared to motivate worry about medical errors. Worry about medical
      errors was a better predictor of intentions to take precautionary actions than
      were risk perceptions. An understanding of how worry influences preventive
      efforts will help in building communication strategies to the public and in
      effectively engaging patients in the role of vigilant partner in care.

PMID- 16569106
TI  - Adherence to antiretroviral therapy: an empirical test of the information
      motivation-behavioral skills model.
AB  - Consistent and nearly perfect adherence is considered an essential requirement
      for HIV-positive patients on antiretroviral therapy (ART) to fully realize its
      life-extending benefits. The current study evaluated a comprehensive model of ART
      adherence--the information-motivation-behavioral skills (IMB) model. This model
      views adherence behavior as a function of the interrelations between adherence
      related information, motivation, and behavioral skills. It hypothesizes that
      adherence-related information and motivation work through adherence-related
      behavioral skills to affect the initiation and maintenance of optimal ART
      adherence. In a series of structural equation models, the IMB model's critical
      constructs and assumptions were evaluated with a sample of 100 HIV-positive
      patients in clinical care. Across all analyses, the authors found support for the
      assumptions of the IMB model of ART adherence. Consistent with the model,
      adherence-related information and motivation related significantly to adherence
      related behavioral skills, and behavioral skills related significantly to self
      reported optimal adherence. Further, as predicted, the effects of information and
      motivation on self-reported adherence were mediated by adherence-related
      behavioral skills. Current study results are explored, and implications for
      adherence promotion interventions based on the model are discussed.

PMID- 16569107
TI  - Risk taking from the participant's perspective: the case of driving and accident
      risk.
AB  - Although perceived health risk plays a prominent role in theories of health
      behavior, its empirical role in risk taking is less clear. In Study 1 (N = 129),
      2 measures of drivers' risk-taking behavior were found to be unrelated to self
      estimates of accident concern but to be related to self-ratings of driving skill
      and the perceived thrill of driving. In Study 2 (N = 405), out of a wide range of
      potential influences, accident concern had the weakest relationship with risk
      taking. The authors concluded that although health risk is a key feature in many
      theories of health behavior and a central focus for researchers and policy
      makers, it may not be such a prominent factor for those actually taking the risk.

PMID- 16569108
TI  - Applying a cognitive behavioral model of health anxiety in a cancer genetics
      service.
AB  - A cognitive-behavioral model of health anxiety was used to investigate reactions
      to genetic counseling for cancer. Participants (N = 218) were asked to complete a
      questionnaire beforehand and 6 months later. There was an overall decrease in
      levels of cancer-related anxiety, although 24% of participants showed increased
      cancer-related anxiety at follow-up. People who had a general tendency to worry
      about their health reported more cancer-related anxiety than those who did not at
      both time points. This health-anxious group also showed a postcounseling anxiety
      reduction, whereas the others showed no significant change. Participants with
      breast or ovarian cancer in their family were more anxious than participants with
      colon cancer in their family. Preexisting beliefs were significant predictors of
      anxiety, consistent with a cognitive-behavioral approach.

PMID- 16569109
TI  - Expressive disclosure and benefit finding among breast cancer patients:
      mechanisms for positive health effects.
AB  - A randomized trial (n = 60; A. L. Stanton, S. Danoff-Burg, L. A. Sworowski, et
      al., 2002) revealed that 4 sessions of written expressive disclosure or benefit
      finding produced lower physical symptom reports and medical appointments for
      cancer-related morbidities at 3-month follow-up among breast cancer patients
      relative to a fact-control condition. The goal of this article is to investigate
      mechanisms underlying these effects. Within-session heart rate habituation
      mediated effects of expressive disclosure on physical symptoms, and greater use
      of negative emotion words in essays predicted a decline in physical symptoms.
      Postwriting mood and use of positive emotion and cognitive mechanism words in
      essays were not significant mediators, although greater cognitive mechanism word
      use was related to greater heart rate habituation and negative emotion word use.

PMID- 16569110
TI  - An association between the DAT1 polymorphism and smoking behavior in young adults
      from the National Longitudinal Study of Adolescent Health.
AB  - Associations between smoking behavior and polymorphisms in the dopaminergic genes
      (DAT1 and DRD2) were tested by using within- and between-family measures of
      allelic transmission in 2,448 young adults from the National Longitudinal Study
      of Adolescent Health. The 9-repeat allele of the dopamine transporter gene
      polymorphism (DAT1) was inversely associated with smoking in samples that
      included all subjects and only those who had initiated smoking, accounting for
      approximately 1% of the variance. Never smokers and current nonsmokers had an
      excess transmission of the 9-repeat allele compared with regular smokers,
      suggesting a protective effect of the 9-repeat allele, which is hypothesized to
      alter synaptic dopamine levels.

PMID- 16569111
TI  - The role of depression symptoms in dialysis withdrawal.
AB  - Among end-stage renal disease (ESRD) patients on hemodialysis, death from
      withdrawal from life-sustaining dialysis is increasingly common. The present
      study's objective was to examine depression as a potential risk factor for
      hemodialysis withdrawal. Two hundred forty ESRD hemodialysis (133 male and 107
      female) patients were followed for an average of 4 years after depression symptom
      assessment. Of these, 18% withdrew from dialysis. Using multivariate survival
      analysis and after controlling for the effects of age (p < .001) and clinical
      variables, the authors found that level of depression symptoms was a unique and
      significant predictive risk factor for the subsequent decision to withdraw from
      dialysis (p < .05). The potential impact that depression may have on the decision
      to withdraw from hemodialysis should be considered by health care providers,
      patient families, and patients.

PMID- 16569112
TI  - Health information on the Internet and people living with HIV/AIDS: information
      evaluation and coping styles.
AB  - Individuals who seek information on the Internet to cope with chronic illness may
      be vulnerable to misinformation and unfounded claims. This study examined the
      association between health-related coping and the evaluation of health
      information. Men (n = 347) and women (n = 72) who were living with HIV/AIDS and
      reported currently using the Internet completed measures assessing their Internet
      use. Health Web sites downloaded from the Internet were also rated for quality of
      information. HIV-positive adults commonly used the Internet to find health
      information (66%) and to learn about clinical trials (25%); they also talked to
      their physicians about information found online (24%). In a multivariate
      analysis, assigning higher credibility to unfounded Internet information was
      predicted by lower incomes, less education, and avoidant coping styles. People
      who cope by avoiding health information may be vulnerable to misinformation and
      unfounded claims that are commonly encountered on the Internet.

PMID- 16569113
TI  - Patients' information needs and decision-making processes: what can be learned
      from genetic counselees?
AB  - This field study investigated the information needs and decision-making
      strategies of 161 genetic counselees interviewed just prior to counseling.
      Patients were interested mostly in information about the outcomes and
      consequences of the alternative options at their disposal and about measures to
      defuse the risks. They wanted mainly information stated with certainty and were
      less interested in probability information. There was no difference in the search
      for information between the alternative eventually chosen and the one not chosen.
      There was a difference, however, among types of decisions and the interest in the
      various categories of information. These findings were interpreted within the
      theoretical model of decision making in natural risky situations (O. Huber,
      1997). Practical implications for shared medical decision making are presented.

PMID- 16569114
TI  - Associations among perceptions of social support, negative affect, and quality of
      sleep in caregivers and noncaregivers.
AB  - The authors used structural equation modeling to examine associations among
      perceptions of negative affect, social support, and quality of sleep in a sample
      of caregivers (n = 175) and noncaregiver control participants (n = 169). The
      authors hypothesized that caregiver status would be related to sleep quality
      directly and also indirectly by way of negative affect and social support. This
      hypothesis was partially supported in that caregiving was found to be indirectly
      related to sleep quality. However, after accounting for the indirect effects of
      negative affect and social support, the direct effect of caregiving on sleep
      quality was no longer statistically significant. The structural model accounted
      for approximately 43% of the variance in sleep quality. The present findings may
      be useful in the development of successful sleep interventions for caregivers.

PMID- 16569115
TI  - Primary- and secondary-control strategies in later life: predicting hospital
      outcomes in men and women.
AB  - Community-dwelling individuals (n = 143, 73-98 years old) were assessed to
      consider if their use of task-specific control strategies predicted hospital
      outcomes in the subsequent 2 years. The authors were interested in whether men
      and women facing health-induced task restrictions benefited equally from the use
      of primary- and secondary-control strategies. Gender interacted with primary
      control strategies; men's more frequent use of these proactive strategies
      generally related to fewer hospital admissions. Gender also interacted with
      secondary-control strategies; women's more frequent use of compensatory (self
      protective) strategies corresponded to fewer hospital admissions and shorter
      hospital stay durations. Taken together, our findings suggest that men benefit by
      adopting certain primary-control strategies and women benefit by adopting certain
      compensatory secondary-control strategies.

PMID- 16569116
TI  - Virtual and physical venues as contexts for HIV risk among rural men who have sex
      with men.
AB  - Rural men who have sex with men (MSM) have few identifiable venues in which to
      congregate and meet potential sex partners. The Internet provides a venue for
      rural MSM to meet, and this is potentially troubling because studies of urban MSM
      suggest that HIV risk is higher for men who date online. The goals of this study
      were to identify venues where rural MSM meet their sexual partners and to examine
      their association with high-risk sexual practices. Six hundred sixty-three
      predominantly single, gay, Caucasian MSM completed an online survey of their
      sexual activities. Results showed that the Internet and bars were the most
      popular venues for meeting sex partners. Highest rates of risk behaviors were
      associated with Internet dating and venues in which immediate sexual encounters
      typically occur, suggesting that prevention in rural areas should target multiple
      risk environments.

PMID- 16569117
TI  - Cortisol deviations in people with burnout before and after psychotherapy: a
      pilot study.
AB  - Burnout is characterized by exhaustion, cynicism, and feelings of reduced
      competence. These complaints may be reflected in disturbances in the main stress
      regulatory endocrine system: the hypothalamus pituitary adrenal (HPA) axis. In
      this study, the HPA-axis hormone cortisol was sampled after awakening and during
      the day in 22 participants with clinical burnout and in 21 healthy controls. The
      cortisol level after awakening was shown to be significantly lower in the burnout
      group as compared with the control group. Cortisol levels during the day did not
      differ. The same sampling procedure was repeated after 14 sessions of
      psychotherapeutic intervention. The intervention led to a significant reduction
      in complaints and to an increase of the initially lowered morning cortisol
      levels. No consistent correlations, however, between the changes in subjective
      complaints and the change in cortisol parameters were found.

PMID- 16569118
TI  - A measurement model of women's behavioral risk taking.
AB  - The current study was designed to gain a better understanding of the nature of
      the relationship between substance use and sexual risk taking within a community
      sample of women (N = 1,004). Using confirmatory factor analysis, the authors
      examined the factor structure of sexual risk behaviors and substance use to
      determine whether they are best conceptualized as domains underlying a single,
      higher order, risk-taking propensity. A 2 higher order factor model (sexual risk
      behavior and substance use) provided the best fit to the data, suggesting that
      these 2 general risk domains are correlated but independent factors. Sensation
      seeking had large general direct effects on the 2 risk domains and large indirect
      effects on the 4 first-order factors and the individual indicators. Negative
      affect had smaller, yet still significant, effects. Impulsivity and anxiety were
      unrelated to sexual health risk domains.

PMID- 16569119
TI  - A family beliefs framework for socially and culturally specific preventive
      interventions with refugee youths and families.
AB  - To assist in designing socially and culturally specific preventive interventions
      for refugee youths and families, this study identified the processes by which
      refugee families adapt and apply family beliefs concerning youths. A grounded
      theory model constructed with ATLAS/ti for Windows and named the family beliefs
      framework describes (a) family beliefs concerning refugee youths, (b) contextual
      factors interacting with these family beliefs, (c) adaptation of family beliefs
      concerning refugee youths, and (d) the interplay of adapting family beliefs and
      behaviors concerning refugee youths. Preventive interventions for refugee youths
      and families would be more socially and culturally specific if they addressed the
      specific processes of adapting family beliefs experienced by refugee youths and
      their families amid transitions and traumas.

PMID- 16569120
TI  - The Bender-Gestalt II.
AB  - In 2003, the Bender-Gestalt II was published. In the present article, the
      revision process is described, and major changes to the test are discussed. These
      changes include additional designs, a memory (recall) phase, Motor and Perception
      supplementary tests, a detailed observation form, a global scoring system, and a
      large, nationally representative normative base. Directions for future research
      are also provided.

PMID- 16569121
TI  - Psychosis proneness, coping, and perceptions of social support.
AB  - The current study examined coping styles and perceived levels of social support
      in hypothetically psychosis-prone individuals. Results suggest that psychosis
      prone individuals did not differ from a comparison group on levels of adaptive
      coping or positive social support but that they did endorse higher rates of
      nonadaptive coping and negative social support compared with the comparison
      group.

PMID- 16569122
TI  - The potential benefits of remaining in school on the long-term mental health
      functioning of physically and sexually abused children: beyond the academic
      domain.
AB  - Community-based population survey data were used to explore whether remaining in
      school, independent of achievement status, was associated with lower rates of
      psychopathology in adulthood among participants self-reporting exposure to child
      physical and/or sexual abuse. Remaining in school, independent of one's
      achievement status, was significantly associated with a lower probability of
      experiencing externalizing but not internalizing disorders. Theoretical and
      educational implications of these results are discussed.

PMID- 16569123
TI  - Familial violence socialization in childhood and later life approval of corporal
      punishment: a cross-cultural perspective.
AB  - The use of corporal punishment has been associated with several negative outcomes
      for children. As a result, scholars have begun to study factors that are
      associated with the approval of corporal punishment. Using data from the
      International Dating Violence Study, the author implemented analysis of
      covariance and multilevel modeling analyses to determine that there were
      significant associations among culture, personal and group experiences of
      familial violence socialization, and attitudes about corporal punishment.

PMID- 16569124
TI  - Factitious disorder on an inpatient psychiatry ward.
AB  - The authors present 6 cases of factitious disorder seen on a general adult
      inpatient psychiatry unit of a university hospital. They review the clinical
      features of this disorder and suggest that factitious disorder is much more
      prevalent among psychiatric inpatients than is commonly recognized. Strategies to
      assist in the diagnosis and management this disorder are detailed.

PMID- 16569125
TI  - Disparity in location of urban mental service providers.
AB  - This article investigates geographic disparities in the location of mental health
      providers in relation to population demographics. Associations between provider
      to-population ratios and demographics were examined with density calculations and
      map algebra. This disparity in geospatial availability of specialists may
      constitute an important barrier for persons seeking mental health care.

PMID- 16569126
TI  - Urban adolescent mothers exposed to community, family, and partner violence:
      prevalence, outcomes, and welfare policy implications.
AB  - The federal welfare reforms of 1996 mandated that all minor adolescent mothers
      receiving cash assistance must attend school and live at home to receive their
      cash grant. Though this law has been in place for over 8 years, little research
      has been done that explores the barriers facing adolescent mothers who try to
      attend school and live at home. Anecdotal and qualitative evidence from welfare
      reform evaluation studies suggests that violence may be just such a barrier. This
      article reviews the recent empirical literature on urban adolescent mothers'
      exposure to multiple forms of violence. The author delineates and critiques the
      existing research on the prevalence of and outcomes linked with exposure to
      community violence, witnessed parental violence, physical abuse within the
      family, and partner violence among this population. The article concludes with
      recommendations for researchers, practitioners, and policy makers in light of the
      reviewed findings.

PMID- 16569127
TI  - Clarifying core characteristics of attachment disorders: a review of current
      research and theory.
AB  - Reactive attachment disorder is a relatively new diagnosis that is not well
      studied. Conflicting ideas about its etiology and presentation pervade the
      theoretical, research, clinical, and popular literature. Clarifying core
      characteristics of this disorder and distinguishing them from comorbid conditions
      are critical for improved diagnosis and treatment of children with attachment
      problems.

PMID- 16569128
TI  - An exploratory study of posttraumatic growth in children following a natural
      disaster.
AB  - This study extends L. G. Calhoun and R. G. Tedeschi's (1998) model of
      posttraumatic growth (PTG), positive change resulting from the struggle with
      trauma, to children by exploring the construct among youngsters who experienced
      Hurricane Floyd and the subsequent flooding. Despite burgeoning interest in PTG,
      few studies have examined the phenomenon among non-adults. This first systematic
      study of PTG in children explores hypothesized linkages among PTG and social
      support, competency beliefs, and ruminative thinking. Results suggest that
      competency beliefs relate to PTG and that a supportive social environment and
      ruminative thinking are associated with positive competency beliefs. Contrary to
      expectations, social support did not relate to rumination. Findings testify to
      the merit of studying the PTG process in children. Clinical implications and
      future directions are considered.

PMID- 16569129
TI  - Survival analyses of social support and trauma among homeless male and female
      veterans who abuse substances.
AB  - This appears to be the 1st study of gender differences in how well various forms
      of trauma and social support predict homeless substance abusers' tenure in the
      community without rehospitalization. Sexual and physical abuses at different
      stages of the life span, combat exposure, and recent traumatic events were
      analyzed with social support factors via Cox's proportional hazard model of
      survival in a 2-year follow-up. The survival models showed similarities and
      dissimilarities in predictors of tenure in the community for women compared to
      men among homeless veterans. Traumata and related factors (e.g., depression and
      suicidal thoughts) were more potent (negative) predictors of tenure, and family
      and friends were more important social supports, for women than for men. Men's
      tenure was more positively associated with job satisfaction and more negatively
      related to substance abuse, combat exposure, cognitive impairments, aggression,
      and physical health problems. The intervention implications of these findings are
      discussed.

PMID- 16569130
TI  - Characterizing aggressive behavior in a forensic population.
AB  - The concept of a dichotomous versus a continuous aggression model continues to be
      debated within the research literature. The Impulsive/Premeditated Aggression
      Scale (IPAS; M. S. Stanford, R. J. Houston, C. W. Mathias, et al., 2003) is a
      newly developed self-report instrument designed to classify an individual's
      aggressive behavior as predominantly premeditated or predominantly impulsive. The
      IPAS consists of 30-items that are scored on a 5-point Likert scale. This study
      used a nonrandom sample of convenience (N = 85) from a forensic state hospital.
      Principal-components analysis of the 30 items revealed 2 distinct factors
      (Impulsive and Premeditated Aggression), which accounted for 33% of the variance.
      The results of this study further validate the bimodal classification of
      aggression through its application to a forensic sample. The implications for
      general assessment, diagnosis, and treatment are discussed.

PMID- 16569131
TI  - Are multiracial adolescents at greater risk? Comparisons of rates, patterns, and
      correlates of substance use and violence between monoracial and multiracial
      adolescents.
AB  - Rates and patterns of substance use and violent behaviors among multiracial
      adolescents were examined and compared with 3 monoracial groups, European,
      African, and Asian Americans. The relationships between ethnic identity and the
      subjective experience of racial discrimination, substance use, and violent
      behavior were also examined. The authors found multiracial adolescents reporting
      higher rates of problem behaviors. Several significant relationships between
      ethnic identity and racial discrimination were found with these problem
      behaviors.

PMID- 16569132
TI  - Diagnostic profiles in outpatient child psychiatry.
AB  - Outpatient child psychiatrists appear to be treating a broadening array of
      complex, highly comorbid, and difficult-to-treat youths. In this study, designed
      to evaluate the current demographic and diagnostic profile of outpatient child
      psychiatric patients 1,292 outpatient records from 8 treatment settings were
      reviewed. Patient age, race, gender, and diagnoses were recorded and analyzed.
      Externalizing disorders (ADHD and/or behavior disorders) were diagnosed most
      frequently, followed by internalizing (depressive and anxiety) disorders.
      Comorbidity was evident in nearly half of all patients, regardless of age.
      Substance abuse was infrequently reported as a comorbid condition. Externalizing
      and internalizing pathology frequently co-occurred. Findings reinforce the need
      for clinician vigilance and thorough assessment of outpatient children and
      adolescents.

PMID- 16569134
TI  - The impact of a multidisciplinary, integrated approach on improving the health
      and quality of care for individuals dealing with multiple chronic conditions.
AB  - This study examined the effects of using a multidisciplinary, integrated, whole
      person, team advocate approach to educate and empower participants with multiple
      chronic illnesses and coordinate, monitor, and support their health care process.
      Individuals (N = 39) from Midwest hospitals participated and completed self
      report instruments. Changes in participants' functioning were also measured with
      diagnostic measures completed by the team advocates. The results indicate that
      the participants' perceptions of physical functioning, physical well-being,
      control, self-efficacy, and life satisfaction increased. Additionally, health
      related behavior changes were reported, and short-term costs were significantly
      lower than projected costs. Finally, the participants rated their health care
      services in the program as more effective than previous health care services.

PMID- 16569133
TI  - Compassion fatigue and psychological distress among social workers: a validation
      study.
AB  - Few studies have focused on caring professionals and their emotional exhaustion
      from working with traumatized clients, referred to as compassion fatigue (CF).
      The present study had 2 goals: (a) to assess the psychometric properties of a CF
      scale, and (b) to examine the scale's predictive validity in a multivariate
      model. The data came from a survey of social workers living in New York City
      following the September 11, 2001, terrorist attacks on the World Trade Center.
      Factor analyses indicated that the CF scale measured multiple dimensions. After
      overlapping items were eliminated, the scale measured 2 key underlying dimensions
      -secondary trauma and job burnout. In a multivariate model, these dimensions were
      related to psychological distress, even after other risk factors were controlled.
      The authors discuss the results in light of increasing the ability of
      professional caregivers to meet the emotional needs of their clients within a
      stressful environment without experiencing CF.

PMID- 16569135
TI  - The impact of treatment intervention on parenting stress in postpartum depressed
      mothers: a prospective study.
AB  - The aim of this study was to evaluate whether treatment intervention for
      postpartum depression impacted maternal parenting stress levels. Twenty-three
      mothers referred for postpartum mood and anxiety disorder to an outpatient
      program were included in the study. Statistically and clinically significant
      decreases in levels of parenting stress were evident at the end of the treatment.
      Subjects' perceptions of their parenting characteristics were found to be a major
      contributor to stress levels. In addition to monitoring of depressive symptoms,
      routine assessment of maternal parenting qualities is recommended to ensure
      healthy child outcomes.

PMID- 16569136
TI  - Perceived congruence between expectations and outcomes: implications for mental
      health among Caribbean immigrants.
AB  - Previous research on the psychological adjustment of immigrants has cited the
      perceived congruence between premigratory expectations and postmigratory
      realities as a primary determinant of psychological well-being. Using a sample of
      137 first-generation Caribbean immigrants, a measure of the perceived congruence
      between expectations and outcomes was developed to examine the relationship
      between perceived congruence in various life domains, and indexes of
      psychological well being, such as anxiety, depression, and life satisfaction.
      Overall, perceived congruence was positively associated with life satisfaction
      and negatively associated with depression. Factor analyses revealed the presence
      of two reliable domains (social and professional) in the congruence measure.
      Perceived congruence in both domains was positively associated with life
      satisfaction, and perceived congruence in the professional domain was negatively
      associated with depression symptoms. Implications of the findings are discussed.

PMID- 16569137
TI  - Hope in times of threat: the case of Israeli and Palestinian youth.
AB  - This study was developed by a group of Israeli and Palestinian researchers for
      the purpose of examining levels and contents of hope among young people in the
      conflicted region of the Middle East. Hope was defined as the interaction between
      wishes and positive future expectations. The differentiation between personal and
      collective hopes, as well as stability and/or change of levels of hope in the
      context of a changing reality, were examined. Data were collected at two points
      of time: during the period of the Oslo Accords talks (1999-2000) and in the time
      of events of the Al-Aksa Intifada (2002). The representative samples in the first
      stage were comprised of 1,183 Palestinian high-school students from the
      Palestinian National Territories, and 1,188 Israeli Jewish students. The
      adolescents' hopes, wishes and expectations for the future are compared and
      discussed from individual, social, and cultural perspectives.

PMID- 16569138
TI  - Emotional effects of sertraline: novel findings revealed by meditation.
AB  - Use of selective serotonin reuptake inhibitors continues to increase, as does
      concern about previously unrecognized, subtle side effects and questions about
      whether these drugs produce effects on healthy subjects. The authors report novel
      emotional effects identified by an experienced, psychologically healthy meditator
      who is a psychiatrist and researcher. On a meditation retreat, the subject
      identified a specific profile of emotional changes related to sertraline use. In
      particular, cognitive abilities and the emotions of fear and anger seemed
      unaffected. However, the emotions of sadness, happiness, rapture, and love were
      dramatically reduced in intensity and duration.

PMID- 16569139
TI  - Mental health needs and treatment of foster youth: barriers and opportunities.
AB  - This article reviews current research on emotional and behavioral disorders among
      children in foster care and summarizes findings regarding utilization of mental
      health services in this population. Barriers to needed care are explored,
      practice and policy implications of lack of care are discussed, and alternative,
      evidence-based treatment options for foster youth are examined and proposed.

PMID- 16569140
TI  - Proactive interference and item similarity in working memory.
AB  - Proactive interference (PI) may influence the predictive utility of working
      memory span tasks. Participants in one experiment (N=70) completed Ravens
      Advanced Progressive Matrices (RAPM) and multiple versions of operation span and
      probed recall, modified for the type of memoranda (digits or words). Changing
      memoranda within- or across-trials released PI, but not doing so permitted PI
      buildup. Scores from PI-build trials, but not PI-release trials, correlated with
      RAPM and accounted for as much variance in RAPM as unmodified tasks. These
      results are consistent with controlled attention and inhibition accounts of
      working memory, and they elucidate a fundamental component of working memory span
      tasks.

PMID- 16569141
TI  - Is the focus of attention in working memory expanded through practice?
AB  - This article reinvestigates the claim by P. Verhaeghen, J. Cerella, and C. Basak
      (2004) that the focus of attention in working memory can be expanded from 1 to 4
      items through practice. Using a modified version of Verhaeghen et al.'s n-back
      paradigm, Experiments 1 and 3 show that a signature of a one-item focus, the time
      cost for switching between items in working memory, persists over practice.
      Verhaeghen et al. reported a shift over practice from a step function to a linear
      slope of reaction times over set size and argued that it reflects the expansion
      of the focus. With an improved counterbalancing scheme, a continuously increasing
      slope was found even without practice in Experiment 2. The results question the
      hypothesis that the focus is expanded through practice. They are in line with
      predictions from a model that distinguishes a one-item focus from a direct-access
      region holding about 4 items.

PMID- 16569142
TI  - Examining the relationship between free recall and immediate serial recall: the
      effect of concurrent task performance.
AB  - In 3 experiments, participants saw lists of 16 words for free recall with or
      without a 6-digit immediate serial recall (ISR) task after each word. Free recall
      was performed under standard visual silent and spoken-aloud conditions
      (Experiment 1), overt rehearsal conditions (Experiment 2), and fixed rehearsal
      conditions (Experiment 3). The authors found that in each experiment, there was
      no effect of ISR on the magnitude of the recency effect, but interleaved ISR
      disrupted free recall of those words that would otherwise be rehearsed. The
      authors conclude that ISR and recency cannot both be outputs from a unitary
      limited-capacity short-term memory store and discuss the possibility that the
      process of rehearsal may be common to both tasks.

PMID- 16569143
TI  - Evaluating models of object-decision priming: evidence from event-related
      potential repetition effects.
AB  - This study was designed to differentiate between structural description and bias
      accounts of performance in the possible/impossible object-decision test. Two
      event-related potential (ERP) studies examined how the visual system processes
      structurally possible and impossible objects. Specifically, the authors
      investigated the effects of object repetition on a series of early posterior
      components during structural (Experiment 1) and functional (Experiment 2)
      encoding and the relationship of these effects to behavioral measures of priming.
      In both experiments, the authors found repetition enhancement of the posterior N1
      and N2 for possible objects only. In addition, the magnitude of the N1 repetition
      effect for possible objects was correlated with priming for possible objects.
      Although the behavioral results were more ambiguous, these ERP results fail to
      support bias models that hold that both possible and impossible objects are
      processed similarly in the visual system. Instead, they support the view that
      priming is supported by a structural description system that encodes the global 3
      dimensional structure of an object.

PMID- 16569144
TI  - What does it take to implicitly prime low-frequency category exemplars?
AB  - Prominent views of implicit priming agree that repetition of category exemplars
      should increase the probability of the exemplar coming to mind on a category
      production test. This prediction has been borne out in the data of numerous
      experiments that have used relatively high-frequency exemplars, but experiments
      that have used lower frequency exemplars have reported reduced or no priming on
      category production tests. Frameworks of memory disagree on why frequency would
      affect priming. The authors report 3 experiments, the first of which shows no
      priming of low-frequency exemplars under circumstances that yield priming of
      higher frequency instances. The second 2 experiments show that low-frequency
      instances can be primed, but the prior experience must bias the comprehension of
      the category label, not the exemplar.

PMID- 16569145
TI  - The generation and resemblance heuristics in face recognition: cooperation and
      competition.
AB  - Like all probabilistic decisions, recognition memory judgments are based on
      inferences about the strength and quality of stimulus familiarity. In recent
      articles, B. W. A. Whittlesea and J. Leboe (2000; J. Leboe & B. W. A. Whittlesea,
      2002) proposed that such memory decisions entail various heuristics, similar to
      well-known heuristics in overt decision making. Using verbal stimulus materials,
      Whittlesea and Leboe illustrated 3 separate memory heuristics: fluency,
      generation, and resemblance. In the present investigation, the authors examined
      the generation and resemblance heuristics in face recognition. In 12 experiments,
      people memorized faces and later performed exclusion (source memory) tasks. Every
      experiment contained natural groups of facial photographs (e.g., Caucasian vs.
      Asian faces), but such groups were not always valid source-memory predictors.
      Instead, across experiments, the potential utility of generation and resemblance
      strategies was systematically varied. People were quite sensitive to such
      variations, changing from one heuristic to another as needed. However, they also
      combined heuristics, both improving and damaging performance across conditions.
      The relevance of recognition decision heuristics to eyewitness memory is
      considered.

PMID- 16569146
TI  - An item gains and losses analysis of false memories suggests critical items
      receive more item-specific processing than list items.
AB  - In a repeated testing paradigm, list items receiving item-specific processing are
      more likely to be recovered across successive tests (item gains), whereas items
      receiving relational processing are likely to be forgotten progressively less on
      successive tests. Moreover, analysis of cumulative-recall curves has shown that
      item-specific processing produces a slower, but steadier rate of recall than
      relational processing. The authors relied on these findings to determine the type
      of processing that both list items and critical lures receive in the Deese
      Roediger-McDermott false memory procedure. The first 2 experiments revealed that
      critical lures produced more item gains, but only the list items resulted in a
      decrease in item losses across successive tests. The critical lures also produced
      slower but steadier cumulative recall. In Experiments 3 and 4, the critical items
      were physically presented during study, which resulted in the lures producing
      progressively fewer losses across successive tests. The authors concluded that
      critical items receive more item-specific processing than list items but that
      unless they are presented in the list, they do not become part of participants'
      organized retrieval scheme.

PMID- 16569147
TI  - Inhibitory deficits in older adults: list-method directed forgetting revisited.
AB  - In list-method directed forgetting, participants are cued to intentionally forget
      a previously studied list while remembering a subsequently presented 2nd list.
      Results from prior research are inconclusive on whether older adults show
      deficits in this type of task. In 3 experiments, the authors reexamined the issue
      and compared younger and older adults' responsiveness to the forget cue. Across
      the experiments, the forget cue was varied within and between participants, the 2
      lists were unrelated and related to each other, and recall of the lists was
      required simultaneously and successively. In none of the 3 experiments did any
      age-related difference in directed forgetting performance emerge. List-method
      directed forgetting is assumed to reflect retrieval inhibition. The present
      results thus challenge the proposal of a general inhibitory deficit in older
      adults' memory performance.

PMID- 16569148
TI  - Category dimensionality and feature knowledge: when more features are learned as
      easily as fewer.
AB  - Three experiments compared the learning of lower-dimensional family resemblance
      categories (4 dimensions) with the learning of higher-dimensional ones (8
      dimensions). Category-learning models incorporating error-driven learning,
      hypothesis testing, or limited capacity attention predict that additional
      dimensions should either increase learning difficulty or decrease learning of
      individual features. Contrary to these predictions, the experiments showed no
      slower learning of high-dimensional categories; instead, subjects learned more
      features from high-dimensional categories than from low-dimensional categories.
      This result obtained both in standard learning with feedback and in
      noncontingent, observational learning. These results show that rather than
      interfering with learning, categories with more dimensions cause individuals to
      learn more. The authors contrast the learning of family resemblance categories
      with learning in classical conditioning and probability learning paradigms, in
      which competition among features is well documented.

PMID- 16569149
TI  - Recency effects as a window to generalization: separating decisional and
      perceptual sequential effects in category learning.
AB  - Accounts of learning and generalization typically focus on factors related to
      lasting changes in representation (i.e., long-term memory). The authors present
      evidence that shorter term effects also play a critical role in determining
      performance and that these recency effects can be subdivided into perceptual and
      decisional components. Experimental results based on a probabilistic category
      structure show that the previous stimulus exerts a contrastive effect on the
      current percept (perceptual recency) and that responses are biased toward or away
      from the previous feedback, depending on the similarity between successive
      stimuli (decisional recency). A method for assessing these recency effects is
      presented that clarifies open questions regarding stimulus generalization and
      perceptual contrast effects in categorization and in other domains.

PMID- 16569150
TI  - Global-scale location and distance estimates: common representations and
      strategies in absolute and relative judgments.
AB  - The authors examined whether absolute and relative judgments about global-scale
      locations and distances were generated from common representations. At the end of
      a 10-week class on the regional geography of the United States, participants
      estimated the latitudes of 16 North American cities and all possible pairwise
      distances between them. Although participants were relative experts, their
      latitude estimates revealed the presence of psychologically based regions with
      large gaps between them and a tendency to stretch North America southward toward
      the equator. The distance estimates revealed the same properties in the
      representation recovered via multidimensional scaling. Though the aggregated
      within- and between-regions distance estimates were fitted by Stevens's law (S.
      S. Stevens, 1957), this was an averaging artifact: The appropriateness of a power
      function to describe distance estimates depended on the regional membership of
      the cities. The authors conclude that plausible reasoning strategies, combined
      with regionalized representations and beliefs about the location of these
      relative to global landmarks, underlie global-scale latitude and distance
      judgments.

PMID- 16569151
TI  - Interpreting instructional cues in task switching procedures: the role of
      mediator retrieval.
AB  - In 3 experiments the role of mediators in task switching with transparent and
      nontransparent cues was examined. Subjects switched between magnitude (greater or
      less than 5) and parity (odd or even) judgments of single digits. A cue-target
      congruency effect indicated mediator use: subjects responded faster to congruent
      cue-target combinations (e.g., ODD-3) than to incongruent cue-target combinations
      (e.g., ODD-4). Experiment 1 revealed significant congruency effects with
      transparent word cues (ODD, EVEN, HIGH, and LOW) and with relatively transparent
      letter cues (O, E, H, and L) but not with nontransparent letter cues (D, V, G,
      and W). Experiment 2 revealed significant congruency effects after subjects who
      were trained with nontransparent letter cues were informed of the relations
      between cues and word mediators halfway through the experiment. Experiment 3
      showed that congruency effects with relatively transparent letter cues diminished
      over 10 sessions of practice, suggesting that subjects used mediators less as
      practice progressed. The results are discussed in terms of the role of mediators
      in interpreting instructional cues.

PMID- 16569152
TI  - The cascaded nature of lexical selection and integration in auditory sentence
      processing.
AB  - An event-related brain potential experiment was carried out to investigate the
      temporal relationship between lexical selection and the semantic integration in
      auditory sentence processing. Participants were presented with spoken sentences
      that ended with a word that was either semantically congruent or anomalous.
      Information about the moment in which a sentence-final word could uniquely be
      identified, its isolation point (IP), was compared with the onset of the elicited
      N400 congruity effect, reflecting semantic integration processing. The results
      revealed that the onset of the N400 effect occurred prior to the IP of the
      sentence-final words. Moreover, the factor early or late IP did not affect the
      onset of the N400. These findings indicate that lexical selection and semantic
      integration are cascading processes, in that semantic integration processing can
      start before the acoustic information allows the selection of a unique candidate
      and seems to be attempted in parallel for multiple candidates that are still
      compatible with the bottom-up acoustic input.

PMID- 16569153
TI  - Phonological activation of category coordinates during speech planning is
      observable in children but not in adults: evidence for cascaded processing.
AB  - There is a long-standing debate in the area of speech production on the question
      of whether only words selected for articulation are phonologically activated (as
      maintained by serial-discrete models) or whether this is also true for their
      semantic competitors (as maintained by forward-cascading and interactive models).
      Past research has addressed this issue by testing whether retrieval of a target
      word (e.g., cat) affects--or is affected by--the processing of a word that is
      phonologically related to a semantic category coordinate of the target (e.g.,
      doll, related to dog) and has consistently failed to obtain such mediated effects
      in adult speakers. The authors present a series of experiments demonstrating that
      mediated effects are present in children (around age 7) and diminish with
      increasing age. This observation provides further evidence for cascaded models of
      lexical retrieval.

PMID- 16569154
TI  - Speech errors reflect newly learned phonotactic constraints.
AB  - Speech errors reveal the speaker's implicit knowledge of phonotactic constraints,
      both languagewide constraints (e.g., /K/ cannot be a syllable onset when one is
      speaking English) and experimentally induced constraints (e.g., /k/ cannot be an
      onset during the experiment). Four experiments investigated the acquisition of
      novel 2nd-order constraints, in which the allowable position of a consonant
      depends on some other property of the syllable (e.g., /k/ can only be an onset if
      the vowel is /I/). Participants recited strings of syllables that exhibited the
      novel constraints throughout a 4-day experiment. Their errors reflected the newly
      learned constraints but not until the 2nd day of training. This contrasts with
      previous research showing that errors become sensitive to 1st-order constraints
      almost immediately. A model that learns to assign phonemes to syllable positions
      is presented. It attributes the relative slowness of the acquisition of 2nd-order
      constraints to the self-interfering property of these constraints.

PMID- 16569155
TI  - A study of relative-position priming with superset primes.
AB  - Four lexical decision experiments are reported that use the masked priming
      paradigm to study the role of letter position information in orthographic
      processing. In Experiments 1 and 2, superset primes, formed by repetition of 1 or
      2 letters of the target (e.g., jusstice-JUSTICE) or by insertion of 1 or 2
      unrelated letters (e.g., juastice-JUSTICE), generated significant priming
      compared with unrelated primes and did not differ significantly from an identity
      priming condition. In Experiment 3, identity primes generated significantly
      faster responses than subset primes formed by removal of 2 letters from the
      target (e.g., jutie-JUSTICE), and subset primes generated faster responses than
      substitution primes formed by substitution of 2 letters of the target with
      unrelated letters (e.g., jumlice-JUSTICE). In Experiment 4, insertion of 3
      unrelated letters continued to generate facilitation relative to unrelated primes
      but significantly less so than the identity prime condition. The authors discuss
      the implications of these results for letter-position coding schemes.

PMID- 16569156
TI  - Vowel processing during silent reading: evidence from eye movements.
AB  - Two eye movement experiments examined whether skilled readers include vowels in
      the early phonological representations used in word recognition during silent
      reading. Target words were presented in sentences preceded by parafoveal previews
      in which the vowel phoneme was concordant or discordant with the vowel phoneme in
      the target word. In Experiment 1, the orthographic vowel differed from the target
      in both the concordant and discordant preview conditions. In Experiment 2, the
      vowel letters in the preview were identical to those in the target word. The
      phonological vowel was ambiguous, however, and the final consonants of the
      previews biased the vowel phoneme either toward or away from the target's vowel
      phoneme. In both experiments, shorter reading times were observed for targets
      preceded by concordant previews than by discordant previews. Implications for
      models of word recognition are discussed.

PMID- 16569157
TI  - Syntactic prediction in language comprehension: evidence from either...or.
AB  - Readers' eye movements were monitored as they read sentences in which two noun
      phrases or two independent clauses were connected by the word or (NP-coordination
      and S-coordination, respectively). The word either could be present or absent
      earlier in the sentence. When either was present, the material immediately
      following or was read more quickly, across both sentence types. In addition,
      there was evidence that readers misanalyzed the S-coordination structure as an NP
      coordination structure only when either was absent. The authors interpret the
      results as indicating that the word either enabled readers to predict the arrival
      of a coordination structure; this predictive activation facilitated processing of
      this structure when it ultimately arrived, and in the case of S-coordination
      sentences, enabled readers to avoid the incorrect NP-coordination analysis. The
      authors argue that these results support parsing theories according to which the
      parser can build predictable syntactic structure before encountering the
      corresponding lexical input.

PMID- 16569158
TI  - The processing of free and bound gender-marked morphemes in speech production:
      evidence from Dutch.
AB  - In many languages, the production of noun phrases requires the selection of
      gender-marked elements like determiners or inflectional suffixes. There is a
      recent debate as to whether the selection of freestanding gender-marked elements,
      such as determiners, follows the same processing mechanisms as the selection of
      bound gender-marked morphemes, such as adjective suffixes. Most of the evidence
      on which this debate is based relates to the gender-congruency effect in picture
      word interference experiments. In the present article, the authors address this
      issue with a pure picture-naming task, extending previous work in German (H.
      Schriefers, J. D. Jescheniak, & A. Hantsch, 2005). The results of the present
      study on noun phrase production in Dutch show that both types of gender-marked
      morphemes are selected via the same basic processing mechanisms.

PMID- 16569159
TI  - Does working memory load lead to greater impulsivity? Commentary on Hinson,
      Jameson, and Whitney (2003).
AB  - Previous research by J. M. Hinson, T. L. Jameson, and P. Whitney (2003)
      demonstrated that a secondary task in a delayed discounting paradigm increased
      subjects' preference for the immediate reward. J. M. Hinson et al. interpreted
      their findings as evidence that working memory load results in greater
      impulsivity. The present authors conducted a reanalysis of the data from J. M.
      Hinson et al.'s Experiment 1 at the individual-subject level. Difference scores
      were calculated by subtracting the digit memory load condition from the control
      condition for k (discounting parameter) and a measure of "erroneous" responses.
      The results indicated that the secondary task increased random responding, which
      in turn can account for the increased mean estimates of k. Thus, the data do not
      support the claim that cognitive load affects impulsivity per se.

PMID- 16569161
TI  - Social perspective-taking skills in maltreated children and adolescents.
AB  - The primary goal of this study was to assess the ability of maltreated school-age
      children and adolescents to understand the thoughts, feelings, and points of view
      of others. Level of egocentrism and social perspective-taking coordination were
      assessed in a group of 49 maltreated and 49 demographically matched nonmaltreated
      children. Twenty-six elementary and 23 high school students in each group were
      individually interviewed and their responses to hypothetical interpersonal
      situations coded for egocentricity and level of perspective-taking ability. The
      findings revealed that maltreated children and adolescents were more egocentric
      and delayed in their social perspective-taking development than their
      nonmaltreated peers and that they reported lower levels of global self-worth.
      However, differences within the group of maltreated children and adolescents
      emerged with regard to negotiating novel relationships, as those with fewer
      internalizing or externalizing symptoms exhibited better skills in this area than
      their peers who displayed more symptoms.

PMID- 16569162
TI  - Trajectories of perceived adult and peer discrimination among Black, Latino, and
      Asian American adolescents: patterns and psychological correlates.
AB  - This article presents results from a 3-year longitudinal study of the growth
      patterns and correlates of perceived discrimination by adults and by peers among
      Black, Latino, and Asian American high school students. Results revealed a linear
      increase over time in levels of perceived discrimination by adults, whereas
      perceptions of discrimination by peers remained stable over time. Asian American
      and non-Puerto Rican Latino adolescents (primarily Dominican) reported higher
      levels of peer and/or adult discrimination than did Puerto Rican youth, whereas
      Black adolescents reported a steeper increase over time in levels of perceived
      discrimination by peers and by adults than did Puerto Rican adolescents. Peer and
      adult discrimination was significantly associated with decreased self-esteem and
      increased depressive symptoms over time. Ethnic identity and ethnicity were found
      to moderate the relationships between perceived discrimination and changes in
      psychological well-being over time. Results underscore the need to include
      perceptions of discrimination when studying the development and well-being of
      ethnic minority adolescents.

PMID- 16569163
TI  - Within-child associations between family income and externalizing and
      internalizing problems.
AB  - Within-child associations between family income and child externalizing and
      internalizing problems were examined using longitudinal data from the NICHD Study
      of Early Child Care and Youth Development (2004a, 2004b; N=1,132). Variations in
      income effects were estimated as a function of whether families were poor,
      whether mothers were partnered, and the number of hours mothers and their
      partners were employed. On average, children had fewer externalizing problems
      during times when their families' incomes were relatively high than during times
      when their families' incomes were relatively low; the estimated benefits of
      increased income were greatest for children who were chronically poor. For both
      externalizing and internalizing problems, income was most strongly associated
      with problems when chronically poor children's mothers were partnered and
      employed.

PMID- 16569164
TI  - Children's attributions of intentions to an invisible agent.
AB  - Children ages 3-9 years were informed that an invisible agent (Princess Alice)
      would help them play a forced-choice game by "telling them, somehow, when they
      chose the wrong box," whereas a matched control group of children were not given
      this supernatural prime. On 2 unexpected event trials, an experimenter triggered
      a simulated unexpected event (i.e., a light turning on/off; a picture falling),
      and children's behavioral response to these events (i.e., moving their hand to
      the opposite box) was coded. Results showed a significant Age GroupxExperimental
      Condition interaction; the only children to reliably alter their behavior in
      response to the unexpected events were the oldest children (M=7 years 4 months),
      who were primed with the invisible agent concept. For children's posttest verbal
      explanations, also, only these children saw the unexpected events as being
      referential and declarative (e.g., "Princess Alice did it because I chose the
      wrong box"). Together, these data suggest that children may not regularly begin
      to see communicative signs as embedded in unexpected events until they are around
      7 years of age.

PMID- 16569165
TI  - What do two-year-olds understand about hidden-object events?
AB  - Preferential-looking studies suggest that by 2 months of age, infants may have
      knowledge about some object properties, such as solidity. Manual search studies
      of toddlers examining these same concepts, however, have failed to provide
      evidence for the same understanding. Investigators have recently attempted to
      reconcile this disparity but failed to control for the visual novelty of test
      outcomes. The current design corrected this problem and also tested toddlers'
      predictions of the object's location. The task involved the same events and
      apparatus that have been used in manual search tasks but used looking as the
      dependent measure. Children looked longer when an agent opened the correct door
      and found no ball than when an incorrect door was opened to reveal no ball. A 2nd
      experiment indicated that children's preferential-looking performance did not
      differ from that in manual search tasks simply because additional response time
      had been allowed to respond. Previous comparisons of looking versus reaching
      tested children's postdiction response to an object in an unexpected location,
      but these findings indicate that toddlers can predict where the object should be.

PMID- 16569166
TI  - Boys withdraw more in one-on-one interactions, whereas girls withdraw more in
      groups.
AB  - Past research predicts that males will be more likely to withdraw in one-on-one
      interactions versus groups, whereas females will be more likely to withdraw in
      groups than in one-on-one interactions. Ninety-eight 10-year-old children engaged
      in a word generation task either in same-sex dyads or in groups. Boys completed
      significantly more words in groups than in dyads, whereas girls' performance was
      similar in the 2 social structures. Confirming the hypothesis, analyses of the
      dynamics of dyads and groups using time spent writing as a measure of effort
      demonstrated that boys withdrew more than girls in dyads, whereas girls withdrew
      more than boys in groups. Furthermore, in groups, girls were more likely than
      boys to focus on one individual. Causal explanations for sex differences in
      preferences for differing social structures are proposed.

PMID- 16569167
TI  - Does Barbie make girls want to be thin? The effect of experimental exposure to
      images of dolls on the body image of 5- to 8-year-old girls.
AB  - The ubiquitous Barbie doll was examined in the present study as a possible cause
      for young girls' body dissatisfaction. A total of 162 girls, from age 5 to age 8,
      were exposed to images of either Barbie dolls, Emme dolls (U.S. size 16), or no
      dolls (baseline control) and then completed assessments of body image. Girls
      exposed to Barbie reported lower body esteem and greater desire for a thinner
      body shape than girls in the other exposure conditions. However, this immediate
      negative impact of Barbie doll was no longer evident in the oldest girls. These
      findings imply that, even if dolls cease to function as aspirational role models
      for older girls, early exposure to dolls epitomizing an unrealistically thin body
      ideal may damage girls' body image, which would contribute to an increased risk
      of disordered eating and weight cycling.

PMID- 16569168
TI  - Unresolved states of mind, disorganized attachment relationships, and disrupted
      interactions of adolescent mothers and their infants.
AB  - The links between unresolved maternal attachment status, disrupted maternal
      interaction in play situations, and disorganized attachment relationships were
      examined in a study of 82 adolescent mother-infant dyads. Maternal interactive
      behavior was measured using the Atypical Maternal Behavior Instrument for
      Assessment and Classification coding system. Additional rating scales were
      developed to correspond to the 5 dimensions of disrupted maternal behavior
      outlined by E. Bronfman, E. Parsons, and K. Lyons-Ruth (1999). A robust
      association was observed between disrupted maternal behavior and disorganized
      attachment. Ratings of disrupted maternal behavior revealed that disorganized
      attachment relationships were strongly related to ratings of fearful/disoriented
      behavior. Moreover, mothers who were unresolved were more likely than not
      unresolved mothers to show disrupted patterns of interaction with their infants.
      Regression analyses suggested that disrupted behavior statistically mediated the
      association between unresolved status and disorganized attachment relationships.

PMID- 16569169
TI  - Parenting and adolescent problem behavior: an integrated model with adolescent
      self-disclosure and perceived parental knowledge as intervening variables.
AB  - Parental monitoring, assessed as (perceived) parental knowledge of the child's
      behavior, has been established as a consistent predictor of problem behavior.
      However, recent research indicates that parental knowledge has more to do with
      adolescents' self-disclosure than with parents' active monitoring. Although these
      findings may suggest that parents exert little influence on adolescents' problem
      behavior, the authors argue that this conclusion is premature, because self
      disclosure may in itself be influenced by parents' rearing style. This study (a)
      examined relations between parenting dimensions and self-disclosure and (b)
      compared 3 models describing the relations among parenting, self-disclosure,
      perceived parental knowledge, and problem behavior. Results in a sample of 10th-
      to 12th-grade students, their parents, and their peers demonstrated that high
      responsiveness, high behavioral control, and low psychological control are
      independent predictors of self-disclosure. In addition, structural equation
      modeling analyses demonstrated that parenting is both indirectly (through self
      disclosure) and directly associated with perceived parental knowledge but is not
      directly related to problem behavior or affiliation with peers engaging in
      problem behavior.

PMID- 16569170
TI  - Relations between neighborhood factors, parenting behaviors, peer deviance, and
      delinquency among serious juvenile offenders.
AB  - The present study examined relations among neighborhood structural and social
      characteristics, parenting practices, peer group affiliations, and delinquency
      among a group of serious adolescent offenders. The sample of 14-18-year-old boys
      (N=488) was composed primarily of economically disadvantaged, ethnic-minority
      youth living in urban communities. The results indicate that weak neighborhood
      social organization is indirectly related to delinquency through its associations
      with parenting behavior and peer deviance and that a focus on just 1 of these
      microsystems can lead to oversimplified models of risk for juvenile offending.
      The authors also find that community social ties may confer both pro- and
      antisocial influences to youth, and they advocate for a broad conceptualization
      of neighborhood social processes as these relate to developmental risk for youth
      living in disadvantaged communities.

PMID- 16569171
TI  - The influence of prior knowledge and repeated questioning on children's long-term
      retention of the details of a pediatric examination.
AB  - Children's recall of the details of pediatric examinations was examined over the
      course of a 6-month interval. Although the 83 4- to 7-year-old participants
      reported a substantial amount of information at each assessment, performance
      declined over time, dropping sharply over the course of 3 months but then
      remaining constant out to the final interview at 6 months. As expected, older
      children provided more total information than younger children did and reported a
      greater proportion of the event components in response to general rather than
      specific questions. However, comparable patterns of remembering and forgetting
      over time were observed at each age level. In addition, no effects of repeated
      questioning--in the form of an interview at 3 months for half of the children-
      were observed on performance at the 6-month assessment. Moreover, children's
      prior knowledge about routine doctor visits was assessed before the checkup for
      half of the participants at each age and was associated with initial but not
      delayed recall. Although knowledge increased with age as expected, it nonetheless
      affected recall over and above the influence of age.

PMID- 16569172
TI  - Effect of anxiety reduction on children's school performance and social
      adjustment.
AB  - This study tested the effect of reductions in children's anxiety over time on
      improvements in school performance and social functioning in the context of
      participation in a cognitive-behavioral intervention program. Participants
      included 40 children with high anxiety (6-13 years of age). Independent
      evaluators, children, and parents rated child anxiety; parents rated school
      performance; and children and parents rated social functioning. Measures were
      completed at preintervention, midintervention, and postintervention. Fixed
      effects regression analyses and random-effects regression analyses indicated that
      decreased anxiety was predictive of improved school performance and social
      functioning over the course of the intervention. These findings suggest that
      changes in anxiety influence trajectories of children's scholastic and social
      functioning.

PMID- 16569173
TI  - Depression, self-esteem, and anger in emerging adulthood: seven-year
      trajectories.
AB  - This study used a school-based community sample (N=920) to examine trajectories
      of depressive symptoms, self-esteem, and expressed anger in the critical years of
      emerging adulthood (ages 18-25). Using data from 5 waves, the authors discovered
      that multilevel models indicated that, on average, depressive symptoms and
      expressed anger declined, whereas self-esteem increased. Between-persons
      predictors of variability in trajectories included gender (gender gaps in
      depressive symptoms and self-esteem narrowed), parents' education, and conflict
      with parents (depressive symptoms and expressed anger improved fastest in
      participants with highly educated parents and in those with higher conflict).
      Across time, increases in social support and marriage were associated with
      increased psychological well-being, whereas longer periods of unemployment were
      connected with higher depression and lower self-esteem. Emerging adulthood is a
      time of improving psychological well-being, but individual trajectories depend on
      specific individual and family characteristics as well as role changes.

PMID- 16569174
TI  - A developmental contextual perspective on identity construction in emerging
      adulthood: change dynamics in commitment formation and commitment evaluation.
AB  - A developmental contextual test of a dual-cycle model of identity formation is
      presented. In addition to a commitment-formation cycle-represented by Marcia's
      (1966) classical dimensions of exploration in breadth and commitment making--the
      model comprises a commitment-evaluation cycle--constituted by 2 additional
      dimensions of exploration in depth and identification with commitment. In a
      sample of 402 college students assessed 4 times over 2 years, both dimensions of
      the commitment-formation cycle and exploration in depth increased across time.
      Identification with commitment showed a slight decrease across time. Latent
      growth curve (LGC) modeling analyses indicated that the 2 identity cycles are
      interwoven in a dynamic interplay that defines identity formation. Contextual
      influences on identity development were identified through a natural experiment.
      Commitment evaluation constituted the core identity cycle in the normative
      progression group (i.e., students who moved on to the sophomore year). Both
      commitment formation and commitment evaluation were at work in the reorientation
      group (i.e., students who repeated their freshman year or changed their major).
      Implications and suggestions for future research are discussed.

PMID- 16569175
TI  - Low self-esteem during adolescence predicts poor health, criminal behavior, and
      limited economic prospects during adulthood.
AB  - Using prospective data from the Dunedin Multidisciplinary Health and Development
      Study birth cohort, the authors found that adolescents with low self-esteem had
      poorer mental and physical health, worse economic prospects, and higher levels of
      criminal behavior during adulthood, compared with adolescents with high self
      esteem. The long-term consequences of self-esteem could not be explained by
      adolescent depression, gender, or socioeconomic status. Moreover, the findings
      held when the outcome variables were assessed using objective measures and
      informant reports; therefore, the findings cannot be explained by shared method
      variance in self-report data. The findings suggest that low self-esteem during
      adolescence predicts negative real-world consequences during adulthood.

PMID- 16569176
TI  - [Storage of thermolabile drugs].

PMID- 16569177
TI  - [The Royal Decree on clinical trials reaches the age of 2].

PMID- 16569178
TI  - [Prescription and preparation of parenteral nutrition at Spanish hospitals].
AB  - OBJECTIVE: To identify habits related to prescription and preparation of
      parenteral nutrition in Spain and their adequacy to current recommendations.
      METHOD: A questionnaire was administered in order to collect information about
      the characteristics of diets used at each hospital and the way they were
      prepared. The questionnaire was available through the web page of the Spanish
      Society of Hospital Pharmacy. RESULTS: Forty five hospitals answered the
      questionnaire. More than 90% of the hospitals reported that they used diets with
      a fixed or standard composition and 66.6% reported that they bought diets
      available in the market with a defined composition. Fifty seven point five per
      cent of the hospitals always prepared "all in one" parenteral nutrition and 37.5%
      prepared them only for adults. A 5% provided the lipids separately, both for
      adults and for children. Forty five per cent of the hospitals reported that they
      did not use organophosphates as source of phosphate. Almost 60% alternate the
      introduction of vitamins and trace elements. Differences were also found
      regarding the type of lipids provided and the use of filters. Most hospitals used
      multi-layer bags and photoprotection. CONCLUSIONS: There is quite a lot of
      diversity in the patterns of prescription and preparation of parenteral nutrition
      in our country. Further consensus documents should be written about these topics.

PMID- 16569179
TI  - [Multicenter study on the prevalence of hyperglycemia among hospitalized patients
      with parenteral nutrition].
AB  - OBJECTIVE: The aim of this cross-sectional national multicentric study was to
      determine the prevalence of hyperglycemia in patients with parenteral nutrition
      and to assess other clinical factors associated with this complication. METHOD:
      All Spanish hospital pharmacy services were invited to participate in the study.
      RESULTS: Twenty eight (28) pharmacy services agreed to participate. The study
      included 442 patients. The prevalence of hyperglycemia (plasma levels > 200
      mg/dL) was 26.7%. Eighty four point two per cent of the patients received less
      than 3.5 mg/kg/minute of glucose, this infusion rate being considered as the safe
      threshold. In most patients, follow-up of glycemia was based on capillary blood
      determination with reactive strips and in 27.6% of the cases in which insulin was
      prescribed, it was added to the parenteral nutrition bag, in full or in part. No
      significant correlations were found between glycemia and the clinical factors
      studied (disorders, fever, medication), except for insulin. CONCLUSIONS: This
      national multicentric study of the prevalence of hyperglycemia among patients
      with parenteral nutrition, leaded by hospital pharmacists, was a joint effort
      aimed to better understand this metabolic complication. Findings are consistent
      with those reported by other authors and have allowed us to describe the current
      situation.

PMID- 16569180
TI  - [Economic assessment of the implementation of a parenteral nutrition protocol for
      patients undergoing intestinal resection by a multidisciplinary team].
AB  - OBJECTIVE: An economic assessment on the impact of total parenteral nutrition
      guidelines developed by the Hospital Nutrition Committee for patients undergoing
      intestinal resection and implemented by a nutritional support multidisciplinary
      team, was conducted. METHOD: A comparative retrospective study of two consecutive
      annual periods before and after the implementation of total parenteral nutrition
      guidelines for patients undergoing intestinal resection developed by the
      Nutrition Committee was carried out. Cost-effectiveness analysis from the
      hospital perspective was performed with the pharmacoeconomic program Pharma
      Decision Hospital. Effectiveness was assessed as nutritional gain and safety
      profile; as well as determination of the costs of acquisition, preparation,
      administration, monitoring and nutritional complications. Sensitivity analysis
      (+/-20%) of effectiveness and hospital stay. RESULTS: Among 326 patients
      hospitalized for intestinal resection, 69 out of 172 (40%) received parenteral
      nutrition during the early period, versus 40 out of 154 (26%) after the surgery
      procedure (p < 0.01). In 79% of the patients with parenteral nutrition, the
      adequacy of the indication was assessed, being adequate in 51.7% and 56.7%,
      respectively (p = 0.66). Nutritional gain before and after surgery was similar
      (78.3 vs. 82.5%, p > 0.05), with patients having less episodes of
      hypophosphatemia postoperatively (60 vs. 38%). Mean total cost per patient before
      and after surgery was 9,180.81 and 7,871.96, respectively. The sensitivity
      analysis confirmed the above results. CONCLUSIONS: The development of total
      parenteral nutrition guidelines by the Nutrition Committee for surgical patients
      undergoing intestinal resection and their implementation by a multidisciplinary
      team improved the use of parenteral nutrition and reduced associated costs, with
      the same nutritional evolution.

PMID- 16569181
TI  - [Stability of an oral liquid morphine formulation for pediatric use].
AB  - OBJECTIVE: The aim of this study the determination of the stability of an oral
      morphine hydrochloride solutions. METHOD: Determinations of a concentrated
      morphine solution of 4 mg/ml and the impact of two temperatures, 4 degrees C
      (refrigerator) and 25 degrees C (room) was analyzed via spectrophotometric
      measurements. RESULTS: Findings showed the high stability of the solutions at 4
      degrees C, since no significant degradation was observed during the 30 days of
      the study, whereas at room temperature stability losses were hardly seen during
      the first 7 days, reaching 6.8% +/- 0.5% after 15 days. CONCLUSIONS: The tested
      morphine solution is stable at 4 degrees C during 30 days, but not at room
      temperature.

PMID- 16569182
TI  - [Maximum stability of thermolabile drugs outside the refrigerator].
AB  - OBJECTIVE: To review the maximum stability of thermolabile drugs at room
      temperature (22-25 degrees C) in order to quickly act in case of breakage of the
      cold chain. METHOD: The study included all drugs available in the pharmacy
      service from August 17, 2004 to October 15 of the same year, date in which the
      review was performed, that had to be kept at a temperature ranging between 2
      degrees and 8 degrees C. Different drug laboratories were contacted and asked for
      written information on the matter. RESULTS: The results are reported in a table.
      One hundred seventy three medicinal products including 83 drugs were reviewed.
      CONCLUSIONS: Some information provided by the pharmaceutical industry allows the
      use of drugs even when the cold chain has been broken. This information must be
      used only in isolated cases, not as a routine.

PMID- 16569183
TI  - [Pharmaceutical care for patients with enteral nutrition].
AB  - OBJECTIVE: To detect potential complications and interactions between drugs and
      enteral nutrition (EN) as to describe the interventions carried out by the
      pharmacist in those circumstances and to propose strategies of improvement.
      METHOD: Prospective assessment of patients admitted to hospital candidates to
      receive EN. The pharmacist worked as part of the team of Endocrinology and
      Nutrition for one month. A data collection form was designed for the study in
      which the following information had to be recorded: NE indications, nutrition
      characteristics (type, route of administration, infusion rate), pharmacological
      therapy, drug/EN interaction and complications. RESULTS: The study included 14
      patients (mean age of 50 +/- 13 years) in which digestive (35.7%) and
      neurological (28.6%) complications were the most frequent indications for EN.
      Eleven patients (78.57%) reported complications associated to EN, mostly
      digestive (57.14%). The main cause for consultation was related to the
      administration of drugs via NGT (nasogastric tube). A total of 77 drugs were
      prescribed, 23 of which were administered in this way, so a guidelines for the
      administration of drugs via nasogastric tube was prepared. CONCLUSIONS: The
      hospital pharmacist can actively cooperate with nutritional support units, given
      the need to assess the nutritional support administered and to manage potential
      complications and interactions between nutritional status, drugs and artificial
      nutrition. The pharmacist also plays a significant role in the prevention and
      identification of problems related to the administration of drugs via NGT.

PMID- 16569184
TI  - [Drug information management through the intranet of a hospital center].
AB  - OBJECTIVE: This paper describes the methodology used for the implementation and
      validation of a network resource incorporated to the intranet of the Hospital, in
      order to retain and disseminate information from the Drug Information Center
      (DIC) of a pharmacy service in a hospital center. METHOD: A working group
      designed the structure, contents, memory needs, priority of access for users and
      a quality assessment questionnaire. RESULTS: The resource developed by the
      working group had a capacity of 70 Gb and its structure was based on HTML
      documents, including files with different format and 12 theme areas. Two levels
      of priority of access were established depending on the user and two persons were
      in charge of the resource. The questionnaire was delivered after three months of
      use. Sixty nine per cent of the users regarded the resource as very useful and
      31%, as useful. The final structure, according to the results of the survey, had
      11 theme areas. CONCLUSIONS: The use of the hospital Intranet in order to include
      and organize DIC information can be very simple and economic. Furthermore, the
      involvement of all the users in its design and structure can facilitate the
      practical use of this tool and improve its quality.

PMID- 16569185
TI  - [Pharmaceutical care for patients requiring nutritional support].

PMID- 16569186
TI  - [Effectiveness of trichloroacetic acid in the bronchopleural fistula].

PMID- 16569187
TI  - [Cutaneous vasculitis due to hypersensitivity probably caused by ketorolac
      trometamol].

PMID- 16569188
TI  - [Comments about pharmaceutical care research].

PMID- 16569189
TI  - Use of an 'evidence-based implementation' strategy to implement evidence-based
      care of asthma into rural district hospital emergency departments.
AB  - INTRODUCTION: To determine if an evidence-based implementation (EBI) could lead
      to the successful implementation of evidence based care for adult asthma in small
      rural district hospitals. METHODS: A controlled trial involving eight small rural
      hospitals (four each in the study and control groups) was conducted.
      Retrospective pre-intervention audits were conducted at all eight hospitals for 7
      months (1 January 2004 to 31 July 2004) and evidence-practice gaps identified. An
      EBI was then used to implement established guidelines for the management of
      asthma in the study hospitals. Post-intervention audits were then performed over
      a period of 7 months (1 October 2004 to 31 April 2005). RESULTS: There were 52
      presentations of asthma in the study hospitals in the pre-implementation phase
      and 47 post-implementation. The corresponding numbers for the control hospitals
      were 46 and 42 respectively. There were no statistically significant differences
      in the severity between the groups. Following the EBI there were significant
      improvements at the study hospitals for the documentation of severity (8% to 62%,
      p <0.001), use of spirometry (12% to 62%, p <0.001) and the use of written short
      term asthma plans (9% to 26%, p = 0.05). There was a decrease in use of
      ipratropium in mild asthma (44% to 30%, p = 0.228), an increase in the use of
      systemic steroids (61% to 72%, p = 0.255) and no change in prescribing
      antibiotics for afebrile patients with asthma (21% to 21% p = 0.956). There was
      no significant change in practice at the control hospitals except for a decrease
      in the use of systemic steroids (48% to 21%, p = 0.011). For the six clinical
      indicators aggregate there was a significant increase in compliance with
      guidelines at the study hospitals (36% to 62%, p < 0.001) but no change at the
      control hospitals (31% to 31%, p = 0.970). CONCLUSION: The pre-intervention
      audits demonstrated low levels of compliance with asthma guidelines across six
      clinical indicators. An EBI significantly improved compliance across these six
      indicators, and no improvement was noted in the control hospitals. This study
      demonstrates that an EBI can alter clinical practice in small rural district
      hospitals.

PMID- 16569192
TI  - Regulation of apoptosis by a prostate-specific and prostate cancer-associated
      noncoding gene, PCGEM1.
AB  - PCGEM1 is a prostate tissue-specific, and prostate cancer-associated noncoding
      RNA (ncRNA) gene. Previous results revealed a significant association of elevated
      PCGEM1 expression levels in prostate cancer cells of African-American patients,
      whose mortality rate is the highest among prostate cancer patients. Functional
      study of PCGEM1 demonstrated a marked increase in colony formation in LNCaP
      prostate cancer cells and NIH3T3 mouse fibroblast cells. This study demonstrates
      that PCGEM1 overexpression in LNCaP cell culture model results in the inhibition
      of apoptosis induced by doxorubicin (DOX). Induction of p53 and p21(Waf1/Cip1) by
      DOX were delayed in LNCaP cells stably overexpressing PCGEM1 (LNCaP-PCGEM1 cells)
      compared to control LNCaP cells. The protein levels of cleaved caspase 7, and
      cleaved PARP were attenuated in DOXtreated LNCaP-PCGEM1 cells compared to control
      LNCaP cells. Similar results were observed in LNCaP cells transiently
      overexpressing PCGEM1. The inhibition of PARP cleavage by PCGEM1 overexpression
      was also observed in LNCaP-PCGEM1 cells incubated with etoposide and sodium
      selenite. Fluorescence-Activated Cell Sorter Annexin-V analysis revealed
      significantly lower percentage of apoptotic cells in DOX-treated LNCaP-PCGEM1
      cells compared to control LNCaP cells. The attenuation of apoptic response
      appears to be androgen dependent in this experimental model, as androgen
      independent variants of LNCaP cells did not exhibit this response. In summary,
      this study provides new insights into cell biologic functions and novel features
      of an ncRNA. Further, these data unravel biological mechanisms of cell
      growth/cell survival-associated functions of this ncRNA in a widely used prostate
      cancer cell culture model.

PMID- 16569194
TI  - Axial (apical-basal) expression of pro-apoptotic and pro-survival genes in the
      lake baikal demosponge Lubomirskia baicalensis.
AB  - Like in all other Metazoa, also in sponges (Porifera) proliferation,
      differentiation, and death of cells are controlled by apoptotic processes, thus
      allowing the establishment of a Bauplan (body plan). The demosponge Lubomirskia
      baicalensis from the Lake Baikal is especially suitable to assess the role of the
      apoptotic molecules, since its grade of construction is highly elaborated into an
      encrusting base and branches composed of modules lined up along the apical-basal
      axis. The four cDNAs, ALG-2, BAK, MA-3, and Bcl-2, were isolated from this sponge
      species. The expression levels of these genes follow characteristic gradients.
      While the proapoptotic genes are highly expressed at the base of the branches and
      comparably low at the top, the pro-survival gene follows an opposite gradient.
      Parallel with the tuned expression of these genes, the activities of the
      apoptosis-executing enzymes caspase-8 (IETDase activity) and caspase-3 (DEVDase
      activity) are lowest at the top of the branch and highest at their base. This
      characteristic expression/activity pattern of the genes/enzymes, which had been
      determined in a few specimens, collected from an unpolluted, natural site,
      appears reversed in specimens collected from an anthropogenically polluted site.
      These findings indicate the involvement of apoptotic proteins in the axis
      formation (branches) in L. baicalensis.

PMID- 16569193
TI  - In vivo bactofection: listeria can function as a DNA-cancer vaccine.
AB  - The development of an effective therapeutic vaccine to induce cancer-specific
      immunity remains an unsolved yet pressing priority requiring novel vaccine
      strategies. Here we have generated a series of vaccines in which bacteria deliver
      a plasmid encoding a tumor antigen under the control of a mammalian promoter in
      an attempt to induce an antitumor immune response. Utilizing a plasmid release
      mechanism involving the suicide of the carrier bacteria, we were able to engineer
      Listeria monocytogenes to induce antitumor immunity to a physiologically relevant
      tumor antigen, the cervical cancer oncoprotein E7. In a mouse model of cervical
      cancer, we were able to slow tumor growth and induce an effector CD8(+) T-cell
      response against the immunodominant epitope for E7. The CD8(+) T cells generated
      could both home to and penetrate the tumor. This is the first demonstration of in
      vivo efficacy of bactofection vectors in treating solid tumors. However, although
      this delivery system was more effective than administering plasmid alone, it was
      not as effective as L. monocytogenes engineered to deliver the E7 protein in
      impacting on established tumor growth.

PMID- 16569195
TI  - Does rapid oligomerization of hepatitis B envelope proteins play a role in
      resistance to proteasome degradation and enhance chronicity?
AB  - This review discusses the nature of hepatitis B and C chronicity from a
      virological perspective. Work described in the literature and our in vitro
      studies of HBV polypeptide morphogenesis lead us to speculate about a role for
      HBsAg complex formation in immune evasion that may be especially important during
      the initial period of infection. Briefly, although viral structural proteins do
      eventually provide epitopes recognized by the host, we suggest that these HBs Ag
      complexes, which may themselves be refractory to proteasomal degradation, are an
      important way by which the virus shields its epitopes and evades early
      recognition by the cellular immune system. This suggests a central strategy by
      which the virus has evolved, structurally, to enable the establishment of
      persistent infection of its host. The concept offers an explanation for the
      nearly unidirectional and rapid kinetics whereby HBV proteins form multimers and
      generate a surplus of viral structures that have not been thought to serve any
      useful structural purpose.

PMID- 16569197
TI  - DNA fingerprinting in the criminal justice system: an overview.
AB  - DNA fingerprinting is a powerful technology that has revolutionized forensic
      science. No two individuals can have an identical DNA pattern except identical
      twins. Such DNA-based technologies have enormous social implications and can help
      in the fight against crime. This technology has experienced many changes over
      time with many advancements occurring. DNA testing is a matter of serious concern
      as it involves ethical issues. This article describes various trends in DNA
      fingerprinting and the current technology used in DNA profiling, possible uses
      and misuses of DNA databanks and ethical issues involved in DNA testing.
      Limitations and problems prevailing in this field are highlighted.

PMID- 16569196
TI  - Evidence of the capability of the CMV enhancer to activate in trans gene
      expression in mammalian cells.
AB  - Studies have reported that an enhancer can act in trans when artificially,
      noncovalently bridged to the promoter by a protein-linked biotin:streptavidin
      complex, or when an enhancer and a promoter are located on separate concatenated
      plasmids. To investigate such transactivation in mammalian cells, we constructed
      CMV promoter-enhancer mutants driving the expression of the EGFP reporter gene
      and transfected cultured cells with various combinations of the mutant PCR
      products; results were analyzed using fluorescence microscopy and flow cytometry.
      Our results show that the CMV enhancer can stimulate transcription in trans, even
      in the absence of physical association of the enhancer and promoter. Furthermore,
      we show that the transactivation of the CMV enhancer can be strengthened by the
      histone deacetylase inhibitor sodium butyrate. Finally, we provide evidence that
      the CMV enhancer can influence, in trans, the activity of heterologous promoters.
      Although different mechanisms may lead to transcriptional activation when the CMV
      enhancer is not covalently linked to the promoter, our results suggest that the
      main mechanism resembles the process of transfection and may be important for
      gene regulation. These findings may have implications in understanding the
      processes that underlie gene therapy because of the potential alteration of
      endogenous gene expression.

PMID- 16569198
TI  - Why ribose was selected as the sugar component of nucleic acids.
AB  - During evolution ribose was selected as the exclusive sugar component of nucleic
      acids. The selection is explained by using molecular models and by eliminating
      most of the other common sugars by looking at their chemical structure and
      envisioning how they would fit in a nucleic acid model. Comparisons of sugar
      pucker conformations and configurations of pentoses indicate that ribose was not
      randomly selected but the only choice, since beta-D-ribose fits best into the
      structure of physiological forms of nucleic acids. In other nucleotides
      containing arabinose, xylose, or lyxose, the C(2)'-OH and/or the C(3)'-OH are
      above the furanose ring, causing steric interference with the bulky base and the
      C(5)'-OH group.

PMID- 16569199
TI  - The lymphatic continuum continues.

PMID- 16569200
TI  - Automated measurement of diameter and contraction waves of cannulated lymphatic
      microvessels.
AB  - BACKGROUND: Studies of lymphatic function often employ collecting lymphatic
      vessels that exhibit large-amplitude, spontaneous contractions. Data from such
      preparations have been analyzed using cardiac pump analogies that require
      accurate determination of vascular dimensions, including external (OD) and
      internal (ID) diameters. These measurements would be facilitated by an accurate
      automated measurement system. METHODS AND RESULTS: A computer-based diameter
      tracking system was developed specifically for lymphatic vessels, with advantages
      over previous automated systems. The system also permits continuous diameter
      tracking at two axial locations, enabling the measurement and analysis of
      contraction wave conduction. The method was validated using spontaneously
      contracting segments of rat thoracic duct which sometimes exhibited conducted
      contraction waves. In such preparations, conduction wave velocity was modulated
      by the axial flow rate and could be easily measured by the tracking system.
      CONCLUSIONS: The method offers improvement and increased convenience over manual
      diameter measurements in lymphatic vessels, with little or no sacrifice in
      accuracy. It should be a useful tool for general studies of collecting lymphatic
      function as well as for the analysis of contraction wave conduction and
      coordination.

PMID- 16569201
TI  - Expression of lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) in
      the human placenta.
AB  - BACKGROUND: Lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) is a
      selective marker for lymphatic endothelium and a homolog of CD44, the hyaluronan
      (HA) receptor. HA in the extracellular matrix plays roles in tissue remodeling,
      development, and homeostasis, and as an HA receptor, LYVE-1 mediated HA
      metabolism might regulate these events. Currently, little is known about the
      lymphatic character within the human placenta. This study therefore determined
      LYVE-1 and other lymphatic markers in human placentas. METHODS AND RESULTS:
      Placentas and villous tissue were fixed and immunostained for human LYVE-1 and
      CD44 and examined by RT-PCR. LYVE-1 was expressed at both protein and mRNA levels
      in trophoblast cells (TC) and in villous core endothelium (VCE). Predominant
      protein expression for LYVE-1 was observed in syncytiotrophoblast cells (TCs) of
      preterm placentas. Neither mRNA or protein for CD44 was expressed. Other blood
      and lymphatic-lineage molecules (VEGF-A, -C, and -D, Flt-1, KDR, Flt-4, and Prox
      1) were examined by RT-PCR. VEGF-A, VEGF-D, and Flt-1 mRNA were observed in TCs
      and VCEs, while mRNA for VEGF-C, KDR, and Flt-4 was mainly observed in VCEs. Prox
      1 was found at the mRNA, but not protein level in TCs and VCEs. Our findings
      indicate (1) the importance of LYVE-1, but not CD44, in regulation of HA
      metabolism in the maternal-fetal interface and fetal circulation, and (2)
      possible dual blood and lymphatic phenotypic characteristics in fetal
      endothelium. These results provide new insights into HA metabolism and lymphatic
      lineage molecule expression in the human placenta.

PMID- 16569202
TI  - Pulmonary air embolization inhibits lung lymph flow by increasing lymphatic
      outflow pressure.
AB  - BACKGROUND: Air embolization of the pulmonary vascular tree increases pulmonary
      microvascular filtration and induces pulmonary edema formation. Flow from
      cannulated pulmonary lymphatic vessels increases significantly following air
      embolization. However, in the intact animal, lymph flows into the venous system
      and the magnitude of lymph flow is directly affected by systemic venous pressure.
      We hypothesized that pulmonary air embolization would lead to systemic venous
      hypertension and that this increase in lymphatic outflow pressure would prevent
      an increase in pulmonary lymph flow. METHODS AND RESULTS: Pulmonary air
      embolization was induced in dogs under general anesthesia. Flow from cannulated
      pulmonary lymphatic vessels was recorded for lymphatic outflow pressure set equal
      to atmospheric pressure (Q(LA)) and for outflow pressure set equal to systemic
      venous pressure (Q(LV)) both before and after embolization. Air embolization
      resulted in significant increases in systemic venous pressure from 6.4 +/- 0.3 to
      12.4 +/- 1.2 mm Hg and in QLA from 48 +/- 9 to 175 +/- 29 microL . min(1).
      However, embolization did not increase Q(LV) (10 +/- 2 vs. 3 +/- 3 microl .
      min(1)). CONCLUSIONS: Pulmonary air embolization impedes pulmonary lymph flow by
      increasing systemic venous pressure and, thereby, contributes to pulmonary edema
      formation.

PMID- 16569203
TI  - 99mTechnetium-SESTAMIBI uptake in malignant lymphomas. Correlation with
      chemotherapy response.
AB  - BACKGROUND: The rationale of the present study is based on the property of
      technetium-SESTAMIBI to enter malignant and other highly metabolic cells, and
      then to be pumped out of them by the multidrug-resistant (MDR) system, strongly
      depending on the expression of the MDR-1 gene encoded P-glycoprotein (Pgp-170).
      METHODS AND RESULTS: Forty-one patients with malignant lymphoma were studied
      before chemotherapy. Images were taken 30 min (early) and 180 min (late) after
      intravenous injection of (99m)Tc-MIBI, and then visually interpreted. They were
      correlated with clinical response defined as chemosensitive (ChS) when a >6 month
      remission was attained, and chemoresistant (ChR) to any other response. Of 41
      patients, 27 had an early positive uptake, 18 (67%) were ChS, and 9 (33%) ChR. Of
      these 27 patients, 19 also had late positive scans; 15 (79%) were ChS, and only 4
      were ChR (p = 0.037). Conversely, 10 of 14 remaining patients with negative early
      scans were ChR. Eight patients had an early positive study; however, the late
      retention of (99m)Tc-MIBI was negative and the relationship to chemotherapy
      response was not conclusive. A breakdown of data was made according to histology.
      Patients with low grade lymphoma had the strongest correlation between (99m)Tc
      MIBI uptake and chemosensitivity. Patients with high grade lymphoma had only a
      trend, and patients with Hodgkin's disease had an indefinable correlation.
      CONCLUSIONS: This study takes advantage of the relationship between the ability
      to uptake and retain (99m)Tc-MIBI, a Pgp-170 substrate, by lymphomatous tumors.
      This attribute, combined with other clinical data, could help to select tailored
      treatments for patients that are likely to be chemoresistant before treatment.

PMID- 16569204
TI  - Intratissular lymphaticovenous anastomoses demonstrated by perioperative
      intramuscular injection of 99mTC-colloids.
AB  - BACKGROUND: The existence of intratissular lymphaticovenous anastomoses has often
      been suggested, but it has never been demonstrated. This study aims at
      demonstrating the presence of such anastomoses. METHODS AND RESULTS: The free
      flap model was used to investigate the drainage of radiolabeled colloid particles
      whose size prevents direct passage to the blood vessels. The tracer was injected
      into the muscle or the skin during the surgical procedure. Blood samples were
      sequentially drawn from the venous pedicle over the 30 minutes that followed the
      tracer injection. The blood samples were counted using a gamma well-counter. In
      all 14 patients, the venous blood radioactivity steadily increased over time.
      Radiochemical analyses performed on the blood samples demonstrated that the
      radioactivity is related to the labeled colloids and not to free pertechnetate.
      Planar imaging performed 24 hours after the surgical procedure showed a
      significant liver uptake, and no accumulation in the area of normal lymphatic
      relays. CONCLUSIONS: As, in the free flap model, there is no lymphatic drainage
      through the classical pathways whatsoever, and since the size of the radiolabeled
      particles prevents them from directly entering the blood stream, the results
      strongly suggest the presence of functional intratissular lymphovenous
      anastomoses.

PMID- 16569207
TI  - Addressing the unmet needs in lymphedema risk management.

PMID- 16569205
TI  - Spontaneous inflammatory cytokine gene expression in normal human peripheral
      blood mononuclear cells.
AB  - Cytokines regulate cellular immune activity and are produced by a variety of
      cells, especially lymphocytes, monocytes, and macrophages. Measurement of
      cytokine levels has yielded useful information on the pathological process of
      different diseases such as AIDS, endotoxic shock, sepsis, asthma, and cancer. It
      may also be of use in the monitoring of disease progression and/or inflammation.
      To determine spontaneous cytokine gene expression in whole blood and PBMCs, whole
      blood was obtained from healthy volunteers and total mRNA was isolated from
      PBMCs. The kinetics of response were determined by sequential testing of cytokine
      gene expression by RT-PCR analysis. Our results demonstrated that isolated and
      incubated PBMCs expressed TNF-alpha and high levels of IL-1beta, IL-6, IL-8, and
      IL-10. In contrast, WB only expressed the mRNA cytokines of TNF-alpha and IL-8 (p
      < 0.05). These results suggest that spontaneous myriad mRNA cytokine expression
      can be avoided with the use of WB incubation and the rapid collection of PBMCs.
      Furthermore, this method should be employed in all cases where the levels of
      cytokine gene expression can be evaluated.

PMID- 16569208
TI  - Bioimpedance analysis: scientific background.

PMID- 16569209
TI  - Bioelectrical impedance analysis: proven utility in lymphedema risk assessment
      and therapeutic monitoring.

PMID- 16569210
TI  - Literature watch.

PMID- 16569212
TI  - Evidence that cytochrome b559 is involved in superoxide production in photosystem
      II: effect of synthetic short-chain plastoquinones in a cytochrome b559 tobacco
      mutant.
AB  - Light-induced production of superoxide (O2*-) in spinach PSII (photosystem II)
      membrane particles was studied using EPR spin-trapping spectroscopy. The presence
      of exogenous PQs (plastoquinones) with a different side-chain length (PQ-n, n
      isoprenoid units in the side-chain) enhanced O2*- production in the following
      order: PQ-1>PQ-2>>PQ-9. In PSII membrane particles isolated from the tobacco cyt
      (cytochrome) b559 mutant which carries a single-point mutation in the beta
      subunit and also has a decreased amount of the alpha-subunit, the effect of PQ-1
      was less than in the wild-type. The increase in LP (low-potential) cyt b559
      content, induced by the incubation of spinach PSII membrane particles at low pH,
      resulted in a significant increase in O2*- formation in the presence of PQ-1,
      whereas it had little effect on O2*- production in the absence of PQ-1. The
      enhancement of O2*- formation induced by PQ-1 was not abolished by DCMU [3-(3,4
      dichlorophenyl)-1,1-dimethylurea]. Under anaerobic conditions, dark oxidation of
      LP cyt b559 increased, as pH was decreased. The presence of molecular oxygen
      significantly enhanced dark oxidation of LP cyt b559. Based on these findings it
      is suggested that short-chain PQs stimulate O2*- production via a mechanism that
      involves electron transfer from Pheo- (pheophytin) to LP cyt b559 and subsequent
      auto-oxidation of LP cyt b559.

PMID- 16569213
TI  - Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet
      derived growth factor receptor-beta and its binding to class IA PI3K in vascular
      smooth muscle cells.
AB  - PI3K (phosphoinositide 3-kinase) activity is involved in Ang (angiotensin) II
      stimulated VSMC (vascular smooth muscle cell) growth and hypertrophy. In the
      present study, we demonstrate that the inhibition of PI3K in VSMCs by expression
      of a dominant-negative p85alpha mutant lacking the p110-binding domain
      (Deltap85), or by treatment of cells with LY294002, inhibited Ang II-stimulated
      PAI-1 (plasminogen activator inhibitor-1) mRNA expression. Using a GST
      (glutathione S-transferase) fusion protein containing the p85 N-terminal SH2 (Src
      homology 2) domain as 'bait' followed by MS/MS (tandem MS), we identified a 70
      kDa fragment of the p70 PDGFR-beta (platelet-derived growth factor receptor-beta)
      as a signalling adapter that is phosphorylated and recruits the p85 subunit of
      PI3K after Ang II stimulation of AT1 (Ang II subtype 1) receptors on VSMCs. This
      fragment of the PDGFR-beta, which has a truncation of its extracellular domain,
      accounted for approx. 15% of the total PDGFR-beta detected in VSMCs with an
      antibody against its cytoplasmic domain. Stimulation of VSMCs with Ang II
      increased tyrosine-phosphorylation of p70 PDGFR-beta at Tyr751 and Tyr1021 and
      increased its binding to p85. PDGF also induced phosphorylation of p70 PDGFR
      beta, a response inhibited by the PDGF tyrosine kinase selective inhibitor,
      AG1296. By contrast, Ang II-induced phosphorylation of the 70 kDa receptor was
      not affected by AG1296. Ang II-stimulated phosphorylation of the p70 PDGFR-beta
      was blocked by the AT1 receptor antagonist, candesartan (CV 11974) and was
      partially inhibited by PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4
      d]pyrimidine}, an Src family kinase inhibitor. Our result suggests that the p70
      PDGFR-beta functions as an adapter that recruits PI3K to the membrane upon AT1
      receptor stimulation.

PMID- 16569214
TI  - Neuronal nitric oxide synthase-induced S-nitrosylation of H-Ras inhibits calcium
      ionophore-mediated extracellular-signal-regulated kinase activity.
AB  - nNOS (neuronal nitric oxide synthase) is a constitutively expressed enzyme
      responsible for the production of NO* from L-arginine and O2. NO* acts as both an
      intra- and an inter-cellular messenger that mediates a variety of signalling
      pathways. Previous studies from our laboratory have demonstrated that nNOS
      production of NO* blocks Ca2+-ionophore-induced activation of ERK1/2
      (extracellular-signal-regulated kinase 1/2) of the mitogen-activated protein
      kinases through a mechanism involving Ras G-proteins and Raf-1 kinase. Herein we
      describe a mechanism by which NO* blocks Ca2+-mediated ERK1/2 activity through
      direct modification of H-Ras. Ca2+-mediated ERK1/2 activation in NO*-producing
      cells could be restored by exogenous expression of constitutively active mitogen
      activated protein kinase kinase 1. In contrast, exogenous expression of
      constitutively active mutants of Raf-1 and H-Ras only partially restored ERK1/2
      activity, by 50% and 10% respectively. On the basis of these findings, we focused
      on NO*-mediated mechanisms of H-Ras inhibition. Assays for GTP loading and H-Ras
      interactions with the Ras-binding domain on Raf-1 demonstrated a decrease in H
      Ras activity in the presence of NO*. We demonstrate that S-nitrosylation of H-Ras
      occurs in nNOS-expressing cells activated with Ca2+ ionophore. Mutation of a
      putative nitrosylation site at Cys118 inhibited S-nitrosylation and restored
      ERK1/2 activity by constitutively active H-Ras even in the presence of NO*. These
      findings indicate that intracellular generation of NO* by nNOS leads to S
      nitrosylation of H-Ras, which interferes with Raf-1 activation and propagation of
      signalling through ERK1/2.

PMID- 16569215
TI  - INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through
      the recruitment of cyclin D1 and histone deacetylases.
AB  - INSM1/IA-1 (insulinoma-associated 1) is a developmentally regulated zinc-finger
      transcription factor, exclusively expressed in the foetal pancreas and nervous
      system, and in tumours of neuroendocrine origin. We have identified an INSM1
      binding site in the neuroD/beta2 promoter and demonstrated transcriptional
      repressor activity of INSM1 by transient transfection assay. A chromatin
      immunoprecipitation assay confirmed that in vivo INSM1 is situated on the
      promoter region of the neuroD/beta2 gene. In an attempt to elucidate the
      molecular mechanism of transcriptional repression by the INSM1 gene, cyclin D1
      was identified as an interacting protein by using a 45-day-old human foetal brain
      cDNA library and a yeast two-hybrid screen. The physical association between
      INSM1 and cyclin D1 was confirmed by in vitro and in vivo pull-down assay. Cyclin
      D1 co-operates with INSM1 and suppresses neuroD/beta2 promoter activity. Co
      immunoprecipitation of INSM1, cyclin D1 and HDACs (histone deacetylases) in
      mammalian cells revealed that INSM1 interacts with HDAC-1 and -3 and that this
      interaction is mediated through cyclin D1. Overexpression of cyclin D1 and HDAC-3
      significantly enhanced the transcriptional repression activity of INSM1 on the
      neuroD/beta2 promoter. A further chromatin immunoprecipitation assay confirmed
      that HDAC-3 occupies this same region of the neuroD/beta2 promoter, by forming a
      transcription complex with INSM1. Thus we conclude that INSM1 recruits cyclin D1
      and HDACs, which confer transcriptional repressor activity.

PMID- 16569216
TI  - Localization of deformed wing virus infection in queen and drone Apis mellifera
      L.
AB  - The distribution of deformed wing virus infection within the honey bee
      reproductive castes (queens, drones) was investigated by in situ hybridization
      and immunohistology from paraffin embedded sections. Digoxygenin or CY5.5
      fluorochrome end-labelled nucleotide probes hybridizing to the 3' portion of the
      DWV genome were used to identify DWV RNA, while a monospecific antibody to the
      DWV-VP1 structural protein was used to identify viral proteins and particles. The
      histological data were confirmed by quantitative RT-PCR of dissected organs.
      Results showed that DWV infection is not restricted to the digestive tract of the
      bee but spread in the whole body, including queen ovaries, queen fat body and
      drone seminal vesicles.

PMID- 16569217
TI  - House dust mite major allergens Der p 1 and Der p 5 activate human airway-derived
      epithelial cells by protease-dependent and protease-independent mechanisms.
AB  - House dust mite allergens (HDM) cause bronchoconstriction in asthma patients and
      induce an inflammatory response in the lungs due to the release of cytokines,
      chemokines and additional mediators. The mechanism how HDM components achieve
      this is largely unknown. The objective of this study was to assess whether HDM
      components of Dermatophagoides pteronissinus with protease activity (Der p 1) and
      unknown enzymatic activity (Der p 2, Der p 5) induce biological responses in a
      human airway-derived epithelial cell line (A549), and if so, to elucidate the
      underlying mechanism(s) of action. A549 cells were incubated with HDM extract,
      Der p 1, recombinant Der p 2 and recombinant Der p 5. Cell desquamation was
      assessed by microscopy. The proinflammatory cytokines, IL-6 and IL-8, were
      measured by ELISA. Intracellular Ca2+ levels were assessed in A549 cells and in
      mouse fibroblasts expressing the human protease activated receptor (PAR)1, PAR2
      or PAR4. HDM extract, Der p 1 and Der p 5 dose-dependently increased the
      production of IL-6 and IL-8. Added simultaneously, Der p 1 and Der p 5 further
      increased the production of IL-6 and IL-8. The action of Der p 1 was blocked by
      cysteine-protease inhibitors, while that of Der p 5 couldn't be blocked by either
      serine- or cysteine protease inhibitors. Der p 5 only induced cell shrinking,
      whereas HDM extract and Der p1 also induced cell desquamation. Der p 2 had no
      effect on A549 cells. Der p 1's protease activity causes desquamation and induced
      the release of IL6 and IL-8 by a mechanism independent of Ca2+ mobilisation and
      PAR activation. Der p 5 exerts a protease-independent activation of A549 that
      involves Ca2+ mobilisation and also leads to the production of these cytokines.
      Together, our data indicate that allergens present in HDM extracts can trigger
      protease-dependent and protease-independent signalling pathways in A549 cells.

PMID- 16569219
TI  - The capacity of short-chain fructo-oligosaccharides to stimulate faecal
      bifidobacteria: a dose-response relationship study in healthy humans.
AB  - BACKGROUND: Short-chain fructo-oligosaccharides (scFOS) are well-known for their
      bifidogenicity. In a large study comprising 200 healthy volunteers, we determined
      the bifidogenic properties of 7 non-digestible carbohydrates administered at a
      dose of 10 g/d in the diet; we analysed dose-response relationships of the
      bifidogenic substrates at doses ranging from 2.5 to 10 g/d in comparison with a
      placebo. The aim of this presentation is to give more details about the dose
      response effects of short-chain fructo-oligosaccharides (scFOS). METHODS: Forty
      healthy volunteers (18 males, 22 females) eating their usual diets were randomly
      divided into 5 groups of 8 subjects and received scFOS at a dose of 2.5, 5.0, 7.5
      and 10 g/d or a placebo for 7 d. Stools were collected before (day (d) 8) and at
      the end (day (d) 15) of sugar consumption, and tolerance was evaluated using a
      daily chart. RESULTS (M +/- SEM): Bifidobacteria counts increase was higher in
      scFOS than in placebo group for all doses tested [2.5 g/d (from 9.15 +/- 0.59 to
      9.39 +/- 0.70; P = 0.02); 5 g/d (from 10.21 +/- 0.21 to 10.67 +/- 0.22; P =
      0.03); 7.5 g/d (from 9.28 +/- 0.49 to 9.85 +/- 0.35;P = 0.01); 10 g/d (from 9.00
      +/- 0.81 to 10.18 +/- 0.60; P = 0.003)]. A significant correlation between the
      ingested dose of scFOS and faecal bifidobacteria counts was observed at d15 (r2 =
      0.307, P < 0.001). Total anaerobes increased at the dose of 10 g/d. No
      significant differences were found for Bacteroides, Lactobacillus, enterobacteria
      or pH in any group. The frequency of digestive symptoms was not different between
      scFOS at any of the doses tested and placebo. Bloating was significantly more
      intense during scFOS ingestion at doses of 2.5 and 5 g/d, but not at doses of 7.5
      and 10 g/d. Excess flatus, borborygmi and abdominal pain did not differ from the
      placebo at any of the doses tested. CONCLUSION: This study showed that scFOS is
      bifidogenic and well tolerated at doses ranging from 2.5 to 10 g/d, and that
      there is a dose-response relationship in healthy volunteers.

PMID- 16569220
TI  - Effects of anti-inflammatory [1, 2, 4]triazolo[4, 3-a] [1, 8]naphthyridine
      derivatives on human stimulated PMN and endothelial cells: an in vitro study.
AB  - BACKGROUND: 124 triazolo [4, 3-a]18naphthyridine derivatives (including NF161 and
      NF177) were tested for anti-inflammatory, analgesic and antipyretic properties
      and for their effects on spontaneous locomotor activity in mice and acute
      gastrolesivity in rats. Both NF161 and NF177 appeared to be anti-inflammatory and
      analgesic agents without toxic effects or acute gastrolesivity, but NF161 showed
      stronger anti-inflammatory activity, whereas NF177 was more active as analgesic.
      METHODS: An EIA kit was used to investigate the ability of NF161 and NF177 to
      affect prostaglandin E2 (PGE2) and prostacyclin (PGI2) production by human
      umbilical vascular endothelial cells (HUVEC). The compounds' effects on the
      production of reactive oxygen species (ROS) by human polymorphonuclear cells
      (PMNs) were studied in an in vitro cell model, evaluating inhibition of
      superoxide anion (O2-*) production induced by N-formylmethionyl-leucyl
      phenylalanine (FMLP). Their effects on PMN adhesion to HUVEC were also
      investigated; they were incubated with PMNs and endothelial cells (EC) and
      challenged by stimuli including Platelet Activating Factor (PAF), FMLP, Phorbol
      Myristate Acetate (PMA), Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin
      1beta (IL-1beta). Adhesion was quantitated by computerized micro-imaging
      fluorescence analysis. RESULTS: Neither compounds modified PGE2 or PGI2
      production induced by IL-1alpha. O2-* production and myeloperoxidase release from
      PMNs stimulated by FMLP was inhibited in a dose- but not time-dependent manner by
      both 18naphthyridine derivatives, NF161 being statistically more active than
      NF177 (P < 0.01). The compounds inhibited adhesion evoked by the pro-inflammatory
      stimuli PAF, FMLP, TNF-alpha and IL-1beta in a concentration-dependent manner in
      the 10(-6)-10(-4)M range, being more active when PAF was used as stimulus and
      inactive when cells were challenged by PMA. Both compounds acted both on PMN and
      HUVEC. CONCLUSION: Considering the interesting anti-inflammatory effects of these
      compounds in in vivo models and the absence of acute gastrolesivity, the study
      improved knowledge of anti-inflammatory properties of NF161 and NF177, also
      demonstrating their potential in vitro, through inhibition of O2-* production,
      myeloperoxidase release and PMN adhesion to HUVEC. Negative results on PG
      production suggest a cyclooxygenase (COX)-independent mechanism.

PMID- 16569221
TI  - Using green fluorescent malaria parasites to screen for permissive vector
      mosquitoes.
AB  - BACKGROUND: The Plasmodium species that infect rodents, particularly Plasmodium
      berghei and Plasmodium yoelii, are useful to investigate host-parasite
      interactions. The mosquito species that act as vectors of human plasmodia in
      South East Asia, Africa and South America show different susceptibilities to
      infection by rodent Plasmodium species. P. berghei and P. yoelii infect both
      Anopheles gambiae and Anopheles stephensi, which are found mainly in Africa and
      Asia, respectively. However, it was reported that P. yoelii can infect the South
      American mosquito, Anopheles albimanus, while P. berghei cannot. METHODS: P.
      berghei lines that express the green fluorescent protein were used to screen for
      mosquitoes that are susceptible to infection by P. berghei. Live mosquitoes were
      examined and screened for the presence of a fluorescent signal in the abdomen.
      Infected mosquitoes were then examined by time-lapse microscopy to reveal the
      dynamic behaviour of sporozoites in haemolymph and extracted salivary glands.
      RESULTS: A single fluorescent oocyst can be detected in live mosquitoes and P.
      berghei can infect A. albimanus. As in other mosquitoes, P. berghei sporozoites
      can float through the haemolymph and invade A. albimanus salivary glands and they
      are infectious in mice after subcutaneous injection. CONCLUSION: Fluorescent
      Plasmodium parasites can be used to rapidly screen susceptible mosquitoes. These
      results open the way to develop a laboratory model in countries where importation
      of A. gambiae and A. stephensi is not allowed.

PMID- 16569222
TI  - Contribution of main causes of death to social inequalities in mortality in the
      whole population of Scania, Sweden.
AB  - BACKGROUND: To more efficiently reduce social inequalities in mortality, it is
      important to establish which causes of death contribute the most to socioeconomic
      mortality differentials. Few studies have investigated which diseases contribute
      to existing socioeconomic mortality differences in specific age groups and none
      were in samples of the whole population, where selection bias is minimized. The
      aim of the present study was to determine which causes of death contribute the
      most to social inequalities in mortality in each age group in the whole
      population of Scania, Sweden. METHODS: Data from LOMAS (Longitudinal Multilevel
      Analysis in Skane) were used to estimate 12-year follow-up mortality rates across
      levels of socioeconomic position (SEP) and workforce participation in 975,938 men
      and women aged 0 to 80 years, during 1991-2002. RESULTS: The results generally
      showed increasing absolute mortality differences between those holding manual and
      non-manual occupations with increasing age, while there were inverted u-shaped
      associations when using relative inequality measures. Cardiovascular diseases
      (CVD) contributed to 52% of the male socioeconomic difference in overall
      mortality, cancer to 18%, external causes to 4% and psychiatric disorders to 3%.
      The corresponding contributions in women were 55%, 21%, 2% and 3%. Additionally,
      those outside the workforce (i.e., students, housewives, disability pensioners,
      and the unemployed) showed a strongly increased risk of future mortality in all
      age groups compared to those inside the workforce. Even though coronary heart
      disease (CHD) played a major contributing role to the mortality differences seen,
      stroke and other types of cardiovascular diseases also made substantial
      contributions. Furthermore, while the most common types of cancers made
      substantial contributions to the socioeconomic mortality differences, in some age
      groups more than half of the differences in cancer mortality could be attributed
      to rarer cancers. CONCLUSION: CHD made a major contribution to the socioeconomic
      differences in overall mortality. However, there were also important
      contributions from diseases with less well understood mechanistic links with SEP
      such as stroke and less-common cancers. Thus, an increased understanding of the
      mechanisms connecting SEP with more rare causes of disease might be important to
      be able to more successfully intervene on socioeconomic differences in health.

PMID- 16569223
TI  - Relationship between impulsivity, hyperactivity and working memory: a
      differential analysis in the rat.
AB  - BACKGROUND: Impulsivity is a behavioural trait that comprises several distinct
      processes. It is a key feature of many psychopathologies such as mania, addictive
      disorders or attention deficit-hyperactivity disorders. To date, the aspects of
      impulsiveness involved in these pathologies have not yet been explicitly defined.
      In these disorders, sensation or drug seeking and cognitive deficits are closely
      related, but the nature of these relationships remains largely unknown. A new
      animal model of impulsiveness based on spontaneous inter-individual differences
      is proposed here to help clarify the relationship between characteristic aspects
      of impulsive-related pathologies. METHODS: Rats were divided into sub-groups
      according to their scores in three operant tasks with varying degrees of
      behavioural inhibition, timing and motor vs. cognitive impulsivity demands. These
      tasks included a fixed consecutive number schedule (ability to complete an action
      to receive a reinforcer), a multiple fixed-interval/extinction schedule of
      reinforcement (high level of responding), and a delayed reward task (delay
      discounting). In addition, measurements of locomotor responses to novelty and to
      amphetamine in a circular corridor, and working memory in an 8-arm radial maze
      were obtained. RESULTS: Substantial behavioural inter-individual differences were
      observed in each task, whereas few inter-task relationships were found. Impulsive
      rats, as defined in a task requiring inhibition of premature responses, presented
      a higher increase in amphetamine-induced locomotion. Reduced working memory
      performance was only observed in hyperactive rats in an extinction schedule.
      CONCLUSION: This novel approach shows that distinct aspects of impulsiveness and
      hyperactivity can be expressed based on large inter-individual differences that
      vary from poorly to highly adapted behaviours ones in a normal population of
      rats. Inhibitory deficit was related to a higher response to psychostimulants a
      characteristic of rats predisposed to amphetamine self-administration and related
      to higher limbic dopaminergic activity, whereas working memory capacity was only
      related to hyperactivity. This approach allows for the identification of
      particular individuals presenting distinct behavioural characteristics of
      impulsive-related psychopathologies. These individuals may be of great interest
      in the modelling of these disorders and the exploration of their neurobiological
      bases.

PMID- 16569225
TI  - Prognostic significance of new onset ascites in patients with pancreatic cancer.
AB  - BACKGROUND: The purpose of this study was to determine risk factors for
      development of malignant ascites and its prognostic significance in patients with
      pancreatic cancer. METHODS: A prospective database was queried to identify
      patients with pancreatic cancer who develop ascites. Stage at presentation, size,
      and location of primary tumor, treatment received and length of survival after
      onset of ascites were determined. RESULTS: A total of 15 patients were
      identified. Of which 4 patients (1 stage II, 3 stage III) underwent
      pancreaticoduodenectomy and manifested with ascites 2, 3, 24 and 47 months after
      surgery (tumor size 2.9 +/- 1.32 cm). All but one of the remaining 11 patients
      (tumor size 4.4 +/- 3.38 cm) presented with metastatic disease, and all developed
      malignant ascites 9 months after diagnosis, dying 2 months later. Resected
      patients lived longer before the onset of ascites, but not after. CONCLUSION:
      Once diagnosed, ascites in pancreatic cancer patients heralds imminent death.
      Limited survival should be considered when determining the aggressiveness of
      further intervention.

PMID- 16569226
TI  - Ten year survival after excision of squamous cell cancer in Zenker's
      diverticulum: report of a case.
AB  - BACKGROUND: Zenker's diverticulum (ZD) has been increasingly recognized as a site
      of primary epithelial malignancy. Pitt in 1896 described the first case. METHODS:
      Between 1990 and 2005, 30 patients affected of esophageal diverticulum were
      referred to our Department. RESULTS: The pathological results revealed one case
      of squamous cell carcinoma. On follow-up 10 years after diverticulectomy alone,
      the patient was alive and well without evidence of recurrence. CONCLUSION: Our
      case reported provides additional data on clinical decision when the tumor is
      well localized without full-thickness penetration or extension to the line of
      resection. In this patient, long-term survival and apparent disease control have
      been effected by diverticulectomy alone. A case of such long survival is very
      rare.

PMID- 16569224
TI  - Prenatal and postnatal tobacco smoke exposure and respiratory health in Russian
      children.
AB  - BACKGROUND: Only few studies have assessed the relative impact of prenatal and
      postnatal exposure to tobacco smoke on the child's later asthma or chronic
      respiratory symptoms and to our knowledge no studies have elaborated respiratory
      infections and allergies in this context. OBJECTIVE: To assess the effects of
      prenatal and postnatal exposure to tobacco smoke on respiratory health of Russian
      school children. METHODS: We studied a population of 5951 children (8 to 12 years
      old) from 9 Russian cities, whose parents answered a questionnaire on their
      children's respiratory health, home environment, and housing characteristics. The
      main health outcomes were asthma, allergies, chronic respiratory symptoms,
      chronic bronchitis, and upper respiratory infections. We used adjusted odds
      ratios (ORs) from logistic regression analyses as measures of effect. RESULTS:
      Prenatal exposure due to maternal smoking had the strongest effects on asthma
      (adjusted OR 2.46, 95% CI 1.19-5.08), chronic bronchitis (adjusted OR 1.45, 95%
      CI 1.08-1.96) and respiratory symptoms, such as wheezing (adjusted OR 1.30, 95%
      CI 0.90-1.89). The associations were weaker for exposure during early-life
      (adjusted ORs 1.38/1.27/1.15 respectively) and after 2 years of age (adjusted ORs
      1.45/1.34/1.18) compared to prenatal exposure and the weakest or non-existent for
      current exposure (adjusted ORs 1.05/1.09/1.06). Upper respiratory infections were
      associated more strongly with early-life exposure (adjusted OR 1.25, 95% CI 1.09
      1.42) than with prenatal (adjusted OR 0.74, 95% CI 0.54-1.01) or current exposure
      (adjusted OR1.05, 95% CI 0.92-1.20). The risk of allergies was also related to
      early life exposure to tobacco smoke (adjusted OR 1.26, 95% CI 1.13-1.42).
      CONCLUSION: Adverse effects of tobacco smoke on asthma, chronic bronchitis, and
      chronic respiratory symptoms are strongest when smoking takes place during
      pregnancy. The relations are weaker for exposure during early-life and after 2
      years of age and weakest or non-existent for current exposure.

PMID- 16569227
TI  - UVPAR: fast detection of functional shifts in duplicate genes.
AB  - BACKGROUND: The imprint of natural selection on gene sequences is often difficult
      to detect. A plethora of methods have been devised to detect genetic changes due
      to selective processes. However, many of those methods depend heavily on
      underlying assumptions regarding the mode of change of DNA sequences and often
      require sophisticated mathematical treatments that made them computationally
      slow. The development of fast and effective methods to detect modifications in
      the selective constraints of genes is therefore of great interest. RESULTS: We
      describe UVPAR, a program designed to quickly test for changes in the functional
      constraints of duplicate genes. Starting with alignments of the proteins encoded
      by couples of duplicate genes in two different species, UVPAR detects the regions
      in which modifications of the functional constraints in the paralogs occurred
      since both species diverged. Sequences can be analyzed with UVPAR in just a few
      minutes on a standard PC computer. To demonstrate the power of the program, we
      first show how the results obtained with UVPAR compare to those based on other
      approaches, using data for vertebrate Hox genes. We then describe a comprehensive
      study of the RBR family of ubiquitin ligases in which we have performed 529
      analyses involving 14 duplicate genes in seven model species. A significant
      increase in the number of functional shifts was observed for the species Danio
      rerio and for the gene Ariadne-2. CONCLUSION: These results show that UVPAR can
      be used to generate sensitive analyses to detect changes in the selection
      constraints acting on paralogs. The high speed of the program allows its
      application to genome-scale analyses.

PMID- 16569228
TI  - Moment-to-moment dynamics of ADHD behaviour in South African children.
AB  - BACKGROUND: The behaviour of children with Attention-Deficit/Hyperactivity
      Disorder is characterized by low predictability of responding. Low behavioural
      predictability is one way of operationalizing intra-individual ADHD-related
      variability. ADHD-related variability may be caused by inefficient behavioural
      selection mechanisms linked to reinforcement and extinction, as suggested by the
      recently published dynamic developmental theory (DDT) of ADHD. DDT argues that
      ADHD is a basic neurobehavioural disorder, caused by dysfunctioning dopamine
      systems. For establishing ADHD as a neurobehavioural disorder, findings from
      studies conducted in Western countries should be replicated in other cultural
      populations. The present study replicated the study conducted in Norway, with
      children from the Limpopo province in the Republic of South Africa. METHODS: Boys
      and girls, aged 6-9 yr, from seven ethnic groups participated. Scores by teachers
      on the Disruptive Behavior Disorders rating scale defined participation in either
      ADHD-hyperactive/impulsive (-HI), ADHD-predominantly inattentive (-PI), or ADHD
      combined (-C) groups. Children below the 86th percentile were matched on gender
      and age and comprised the non-ADHD group. The children completed a computerized
      game-like task where mouse clicks on one of two squares on the screen resulted in
      delivery of a reinforcer according to a variable interval schedule of
      reinforcement. Reinforcers were cartoon pictures presented on the screen together
      with a sound. Predictability of response location and timing were measured in
      terms of explained variance. RESULTS: Overall, the results replicated findings
      from Norway. Specifically, the ADHD-C group showed significantly lower
      predictability of responding than the non-ADHD group, while the ADHD-HI and the
      ADHD-PI groups were in-between. In accordance with the previous study, response
      location, but not response timing, was a sensitive behavioural measure. There
      were no significant gender differences. Cartoon pictures were effective
      reinforcers as the non-ADHD group showed learning of the task. There was no
      relation between behavioural predictability and motor functions. CONCLUSION: The
      present study makes a strong case for ADHD as a basic, neurobehavioural disorder,
      not a cultural phenomenon, by replicating findings from a wealthy Western country
      in a poor province of a developing country. The results were, generally, in line
      with predictions from the dynamic developmental theory of ADHD by indicating that
      reinforcers were less efficient in the ADHD group than in the non-ADHD group.
      Finally, the results substantiated ADHD-related variability as an etiologically
      important characteristic of ADHD behaviour.

PMID- 16569229
TI  - Interferon-gamma increases neuronal death in response to amyloid-beta1-42.
AB  - BACKGROUND: Alzheimer's disease is a neurodegenerative disorder characterized by
      a progressive cognitive impairment, the consequence of neuronal dysfunction and
      ultimately the death of neurons. The amyloid hypothesis proposes that neuronal
      damage results from the accumulation of insoluble, hydrophobic, fibrillar
      peptides such as amyloid-beta1-42. These peptides activate enzymes resulting in a
      cascade of second messengers including prostaglandins and platelet-activating
      factor. Apoptosis of neurons is thought to follow as a consequence of the
      uncontrolled release of second messengers. Biochemical, histopathological and
      genetic studies suggest that pro-inflammatory cytokines play a role in
      neurodegeneration during Alzheimer's disease. In the current study we examined
      the effects of interferon (IFN)-gamma, tumour necrosis factor (TNF)alpha,
      interleukin (IL)-1beta and IL-6 on neurons. METHODS: Primary murine cortical or
      cerebellar neurons, or human SH-SY5Y neuroblastoma cells, were grown in vitro.
      Neurons were treated with cytokines prior to incubation with different neuronal
      insults. Cell survival, caspase-3 activity (a measure of apoptosis) and
      prostaglandin production were measured. Immunoblots were used to determine the
      effects of cytokines on the levels of cytoplasmic phospholipase A2 or
      phospholipase C gamma-1. RESULTS: While none of the cytokines tested were
      directly neurotoxic, pre-treatment with IFN-gamma sensitised neurons to the toxic
      effects of amyloid-beta1-42 or HuPrP82-146 (a neurotoxic peptide found in prion
      diseases). The effects of IFN-gamma were seen on cortical and cerebellar neurons,
      and on SH-SY5Y neuroblastoma cells. However, pre-treatment with IFN-gamma did not
      affect the sensitivity to neurons treated with staurosporine or hydrogen
      peroxide. Pre-treatment with IFN-gamma increased the levels of cytoplasmic
      phospholipase A2 in SH-SY5Y cells and increased prostaglandin E2 production in
      response to amyloid-beta1-42. CONCLUSION: Treatment of neuronal cells with IFN
      gamma increased neuronal death in response to amyloid-beta1-42 or HuPrP82-146.
      IFN-gamma increased the levels of cytoplasmic phospholipase A2 in cultured
      neuronal cells and increased expression of cytoplasmic phospholipase A2 was
      associated with increased production of prostaglandin E2 in response to amyloid
      beta1-42 or HuPrP82-146. Such observations suggest that IFN-gamma produced within
      the brain may increase neuronal loss in Alzheimer's disease.

PMID- 16569230
TI  - LS-NMF: a modified non-negative matrix factorization algorithm utilizing
      uncertainty estimates.
AB  - BACKGROUND: Non-negative matrix factorisation (NMF), a machine learning
      algorithm, has been applied to the analysis of microarray data. A key feature of
      NMF is the ability to identify patterns that together explain the data as a
      linear combination of expression signatures. Microarray data generally includes
      individual estimates of uncertainty for each gene in each condition, however NMF
      does not exploit this information. Previous work has shown that such
      uncertainties can be extremely valuable for pattern recognition. RESULTS: We have
      created a new algorithm, least squares non-negative matrix factorization, LS-NMF,
      which integrates uncertainty measurements of gene expression data into NMF
      updating rules. While the LS-NMF algorithm maintains the advantages of original
      NMF algorithm, such as easy implementation and a guaranteed locally optimal
      solution, the performance in terms of linking functionally related genes has been
      improved. LS-NMF exceeds NMF significantly in terms of identifying functionally
      related genes as determined from annotations in the MIPS database. CONCLUSION:
      Uncertainty measurements on gene expression data provide valuable information for
      data analysis, and use of this information in the LS-NMF algorithm significantly
      improves the power of the NMF technique.

PMID- 16569231
TI  - Lack of association between putative transporter gene polymorphisms in Plasmodium
      falciparum and chloroquine resistance in imported malaria isolates from Africa.
AB  - BACKGROUND: Plasmodium falciparum drug resistance represents a major health
      problem in malaria endemic countries. The mechanisms of resistance are not fully
      elucidated. Recently, an association between putative transporter gene
      polymorphisms and in vitro response to chloroquine (CQ) and quinine has been
      reported in culture-adapted, cloned isolates from various geographical origins.
      However, this was not confirmed in another study performed on isolates from a
      defined region in Thailand. METHODS: This study tried to find an association
      between putative transporters gene polymorphisms with in vitro response to CQ and
      pfcrt genotype in isolates originating from various African countries. To avoid
      biases of parasites adaptation in culture, fresh isolates obtained from
      symptomatic, malaria-infected travellers returning from Africa to France were
      used. Monoclonal isolates included in the study were selected using a msp-2
      fragment analysis method. In vitro susceptibility to CQ, single nucleotide
      polymorphisms and microsatellite polymorphisms in pfcrt, pfmdr1 and six putative
      transporter genes were established in 27 isolates and three reference strains.
      RESULTS: Polymorphism of pfcrt at positions 76 and 220 showed a significant
      association with in vitro chloroquine resistance (P < .02 and P < .05
      respectively). Polymorphism of pfmdr1 at position 86 showed an equally
      significant association with in vitro chloroquine response (P < .05). No
      association was found between SNPs or microsatellite polymorphisms of putative
      transporter genes and in vitro CQR or pfcrt genotype in imported malaria isolates
      from Africa. CONCLUSION: The previously described association between putative
      transporter gene polymorphisms and in vitro response to chloroquine (CQ) was not
      confirmed in the present study.

PMID- 16569232
TI  - Serious infections in children: an incidence study in family practice.
AB  - BACKGROUND: Information on the incidence of serious infections in children in
      general practice is scarce. However, estimates on the incidence of disease are
      important for several reasons, for example to assess the burden of disease or as
      a basis of diagnostic research. We therefore estimated the incidence of serious
      infections in general practice in Belgium. METHODS: Intego is a morbidity
      registration network, in which 51 general practitioners continuously register all
      diagnoses and additional data in their electronic medical records. Serious
      infections were defined as pneumonia, sepsis, meningitis, pyelonephritis and
      osteomyelitis. Incidences are calculated for the period of 1998 to 2002, per 1000
      patients in the yearly contact group, which is the group of patients that
      consulted their GP at least once that year, and in the practice population, which
      is the estimated true population of that practice. RESULTS: The incidence of all
      infectious diseases peaks in children between 0 and 4 years, with 1731 infections
      per 1000 children per year in the yearly contact group. Incidence drops with
      increasing age: 972 infections per 1000 children per year in children between 5
      and 9 years old, and 732 in children between 10 and 14 years old. The same
      decline in incidence is observed in the subgroup of serious infections: 21
      infections per 1000 children per year in children between 0 and 4 years, 12 in
      children between 5 and 9 years and 5 in children between 10 and 14 years. The
      results for the estimated practice population are respectively 17, 9 and 4
      serious infections per 1000 children per year. CONCLUSION: In contrast to the
      total incidence of acute infections, serious infections are rare, around 1% per
      year. Children younger than 4 years old have the highest risk for serious
      infections, and incidences of some infections are different for boys and girls.

PMID- 16569233
TI  - In vitro cytotoxicity of Manville Code 100 glass fibers: effect of fiber length
      on human alveolar macrophages.
AB  - BACKGROUND: Synthetic vitreous fibers (SVFs) are inorganic noncrystalline
      materials widely used in residential and industrial settings for insulation,
      filtration, and reinforcement purposes. SVFs conventionally include three major
      categories: fibrous glass, rock/slag/stone (mineral) wool, and ceramic fibers.
      Previous in vitro studies from our laboratory demonstrated length-dependent
      cytotoxic effects of glass fibers on rat alveolar macrophages which were possibly
      associated with incomplete phagocytosis of fibers >or= 17 microm in length. The
      purpose of this study was to examine the influence of fiber length on primary
      human alveolar macrophages, which are larger in diameter than rat macrophages,
      using length-classified Manville Code 100 glass fibers (8, 10, 16, and 20
      microm). It was hypothesized that complete engulfment of fibers by human alveolar
      macrophages could decrease fiber cytotoxicity; i.e. shorter fibers that can be
      completely engulfed might not be as cytotoxic as longer fibers. Human alveolar
      macrophages, obtained by segmental bronchoalveolar lavage of healthy, non-smoking
      volunteers, were treated with three different concentrations (determined by fiber
      number) of the sized fibers in vitro. Cytotoxicity was assessed by monitoring
      cytosolic lactate dehydrogenase release and loss of function as indicated by a
      decrease in zymosan-stimulated chemiluminescence. RESULTS: Microscopic analysis
      indicated that human alveolar macrophages completely engulfed glass fibers of the
      20 microm length. All fiber length fractions tested exhibited equal cytotoxicity
      on a per fiber basis, i.e. increasing lactate dehydrogenase and decreasing
      chemiluminescence in the same concentration-dependent fashion. CONCLUSION: The
      data suggest that due to the larger diameter of human alveolar macrophages,
      compared to rat alveolar macrophages, complete phagocytosis of longer fibers can
      occur with the human cells. Neither incomplete phagocytosis nor length-dependent
      toxicity was observed in fiber-exposed human macrophage cultures. In contrast,
      rat macrophages exhibited both incomplete phagocytosis of long fibers and length
      dependent toxicity. The results of the human and rat cell studies suggest that
      incomplete engulfment may enhance cytotoxicity of fiber glass. However, the
      possibility should not be ruled out that differences between human versus rat
      macrophages other than cell diameter could account for differences in fiber
      effects.

PMID- 16569234
TI  - Advances and challenges in predicting the impact of lymphatic filariasis
      elimination programmes by mathematical modelling.
AB  - Mathematical simulation models for transmission and control of lymphatic
      filariasis are useful tools for studying the prospects of lymphatic filariasis
      elimination. Two simulation models are currently being used. The first, EPIFIL,
      is a population-based, deterministic model that simulates average trends in
      infection intensity over time. The second, LYMFASIM, is an individual-based,
      stochastic model that simulates acquisition and loss of infection for each
      individual in the simulated population, taking account of individual
      characteristics. For settings like Pondicherry (India), where Wuchereria
      bancrofti infection is transmitted by Culex quinquefasciatus, the models give
      similar predictions of the coverage and number of treatment rounds required to
      bring microfilaraemia prevalence below a level of 0.5%. Nevertheless, published
      estimates of the duration of mass treatment required for elimination differed,
      due to the use of different indicators for elimination (EPIFIL: microfilaraemia
      prevalence < 0.5% after the last treatment; LYMFASIM: reduction of
      microfilaraemia prevalence to zero, within 40 years after the start of mass
      treatment). The two main challenges for future modelling work are: 1)
      quantification and validation of the models for other regions, for investigation
      of elimination prospects in situations with other vector-parasite combinations
      and endemicity levels than in Pondicherry; 2) application of the models to
      address a range of programmatic issues related to the monitoring and evaluation
      of ongoing control programmes. The models' usefulness could be enhanced by
      several extensions; inclusion of different diagnostic tests and natural history
      of disease in the models is of particular relevance.

PMID- 16569235
TI  - The Gaggle: an open-source software system for integrating bioinformatics
      software and data sources.
AB  - BACKGROUND: Systems biologists work with many kinds of data, from many different
      sources, using a variety of software tools. Each of these tools typically excels
      at one type of analysis, such as of microarrays, of metabolic networks and of
      predicted protein structure. A crucial challenge is to combine the capabilities
      of these (and other forthcoming) data resources and tools to create a data
      exploration and analysis environment that does justice to the variety and
      complexity of systems biology data sets. A solution to this problem should
      recognize that data types, formats and software in this high throughput age of
      biology are constantly changing. RESULTS: In this paper we describe the Gaggle -a
      simple, open-source Java software environment that helps to solve the problem of
      software and database integration. Guided by the classic software engineering
      strategy of separation of concerns and a policy of semantic flexibility, it
      integrates existing popular programs and web resources into a user-friendly,
      easily-extended environment. We demonstrate that four simple data types (names,
      matrices, networks, and associative arrays) are sufficient to bring together
      diverse databases and software. We highlight some capabilities of the Gaggle with
      an exploration of Helicobacter pylori pathogenesis genes, in which we identify a
      putative ricin-like protein -a discovery made possible by simultaneous data
      exploration using a wide range of publicly available data and a variety of
      popular bioinformatics software tools. CONCLUSION: We have integrated diverse
      databases (for example, KEGG, BioCyc, String) and software (Cytoscape,
      DataMatrixViewer, R statistical environment, and TIGR Microarray Expression
      Viewer). Through this loose coupling of diverse software and databases the Gaggle
      enables simultaneous exploration of experimental data (mRNA and protein
      abundance, protein-protein and protein-DNA interactions), functional associations
      (operon, chromosomal proximity, phylogenetic pattern), metabolic pathways (KEGG)
      and Pubmed abstracts (STRING web resource), creating an exploratory environment
      useful to 'web browser and spreadsheet biologists', to statistically savvy
      computational biologists, and those in between. The Gaggle uses Java RMI and Java
      Web Start technologies and can be found at http://gaggle.systemsbiology.net.

PMID- 16569236
TI  - Estrogen receptors alpha and beta in rat placenta: detection by RT-PCR, real time
      PCR and Western blotting.
AB  - BACKGROUND: High levels of estrogens during pregnancy not only retard placental
      and fetal growth but can lead to reproductive tract abnormalities in male
      progeny. Estrogens act through estrogen receptors (ER) to modulate the
      transcription of target genes. These ER exist in two isoforms, ER alpha and ER
      beta and recently several variants of these isoforms have been identified.
      METHODS: The expressions of ER isoforms and variants have been studied in rat
      placenta at 16, 19 and 21 days gestation (dg). Gene expression was assessed using
      RT-PCR and real time PCR while protein expression was studied using Western
      blotting followed by immunodetection. Placental homogenates were probed with: a
      monoclonal antibody raised against the steroid binding domain of the ER alpha (ER
      alpha -S), a monoclonal antibody raised against the hinge region of ER alpha (ER
      alpha -H) and a polyclonal antibody raised against the amino terminus of ER beta.
      RESULTS: ER alpha and ER beta mRNA and protein were detected from as early as 16
      dg. Two PCR products were detected for ER alpha, one for the wild type ER alpha,
      and a smaller variant. Real time PCR results suggested the presence of a single
      product for ER beta. The antibodies used for detection of ER alpha protein both
      identified a single 67 kDa isoform; however a second 54 kDa band, which may be an
      ER alpha variant, was identified when using the ER alpha -H antibody. The
      abundance of both ER alpha bands decreased significantly between 16 and 19 dg. As
      for ER beta, four bands (76, 59, 54 and 41 kDa) were detected. The abundance of
      the 59 and 54 kDa bands decreased significantly between 16 and 19 dg. CONCLUSION:
      This study shows that both ER protein isoforms and their variants are present in
      rat placenta. The decrease in their expression near parturition suggests that the
      placenta may be relatively unresponsive to estrogens at this stage.

PMID- 16569237
TI  - Protein-lipid interactions: correlation of a predictive algorithm for lipid
      binding sites with three-dimensional structural data.
AB  - BACKGROUND: Over the past decade our laboratory has focused on understanding how
      soluble cytoskeleton-associated proteins interact with membranes and other lipid
      aggregates. Many protein domains mediating specific cell membrane interactions
      appear by fluorescence microscopy and other precision techniques to be partially
      inserted into the lipid bilayer. It is unclear whether these protein-lipid
      interactions are dependent on shared protein motifs or unique regional
      physiochemistry, or are due to more global characteristics of the protein.
      RESULTS: We have developed a novel computational program that predicts a
      protein's lipid-binding site(s) from primary sequence data. Hydrophobic labeling,
      Fourier transform infrared spectroscopy (FTIR), film balance, T-jump, CD
      spectroscopy and calorimetry experiments confirm that the interfaces predicted
      for several key cytoskeletal proteins (alpha-actinin, Arp2, CapZ, talin and
      vinculin) partially insert into lipid aggregates. The validity of these
      predictions is supported by an analysis of the available three-dimensional
      structural data. The lipid interfaces predicted by our algorithm generally
      contain energetically favorable secondary structures (e.g., an amphipathic alpha
      helix flanked by a flexible hinge or loop region), are solvent-exposed in the
      intact protein, and possess favorable local or global electrostatic properties.
      CONCLUSION: At present, there are few reliable methods to determine the region of
      a protein that mediates biologically important interactions with lipids or lipid
      aggregates. Our matrix-based algorithm predicts lipid interaction sites that are
      consistent with the available biochemical and structural data. To determine
      whether these sites are indeed correctly identified, and whether use of the
      algorithm can be safely extended to other classes of proteins, will require
      further mapping of these sites, including genetic manipulation and/or targeted
      crystallography.

PMID- 16569238
TI  - Coordinate regulation of fibronectin matrix assembly by the plasminogen activator
      system and vitronectin in human osteosarcoma cells.
AB  - BACKGROUND: Plasminogen activators are known to play a key role in the remodeling
      of bone matrix which occurs during tumor progression, bone metastasis and bone
      growth. Dysfunctional remodeling of bone matrix gives rise to the osteoblastic
      and osteolytic lesions seen in association with metastatic cancers. The molecular
      mechanisms responsible for the development of these lesions are not well
      understood. Studies were undertaken to address the role of the plasminogen
      activator system in the regulation of fibronectin matrix assembly in the
      osteoblast-like cell line, MG-63. RESULTS: Treatment of MG-63 cells with P25, a
      peptide ligand for uPAR, resulted in an increase in assembly of fibronectin
      matrix which was associated with an increase in the number of activated beta1
      integrins on the cell surface. Overexpression of uPAR in MG-63 cells increased
      the effect of P25 on fibronectin matrix assembly and beta1 integrin activation.
      P25 had no effect on uPAR null fibroblasts, confirming a role for uPAR in this
      process. The addition of plasminogen activator inhibitor Type I (PAI-1) to cells
      increased the P25-induced fibronectin polymerization, as well as the number of
      activated integrins. This positive regulation of PAI-1 on fibronectin assembly
      was independent of PAI-1's anti-proteinase activity, but acted through PAI-1
      binding to the somatomedin B domain of vitronectin. CONCLUSION: These results
      indicate that vitronectin modulates fibronectin matrix assembly in osteosarcoma
      cells through a novel mechanism involving cross-talk through the plasminogen
      activator system.

PMID- 16569239
TI  - Uneven dietary development: linking the policies and processes of globalization
      with the nutrition transition, obesity and diet-related chronic diseases.
AB  - In a "nutrition transition", the consumption of foods high in fats and sweeteners
      is increasing throughout the developing world. The transition, implicated in the
      rapid rise of obesity and diet-related chronic diseases worldwide, is rooted in
      the processes of globalization. Globalization affects the nature of agri-food
      systems, thereby altering the quantity, type, cost and desirability of foods
      available for consumption. Understanding the links between globalization and the
      nutrition transition is therefore necessary to help policy makers develop
      policies, including food policies, for addressing the global burden of chronic
      disease. While the subject has been much discussed, tracing the specific pathways
      between globalization and dietary change remains a challenge. To help address
      this challenge, this paper explores how one of the central mechanisms of
      globalization, the integration of the global marketplace, is affecting the
      specific diet patterns. Focusing on middle-income countries, it highlights the
      importance of three major processes of market integration: (I) production and
      trade of agricultural goods; (II) foreign direct investment in food processing
      and retailing; and (III) global food advertising and promotion. The paper reveals
      how specific policies implemented to advance the globalization agenda account in
      part for some recent trends in the global diet. Agricultural production and trade
      policies have enabled more vegetable oil consumption; policies on foreign direct
      investment have facilitated higher consumption of highly-processed foods, as has
      global food marketing. These dietary outcomes also reflect the socioeconomic and
      cultural context in which these policies are operating. An important finding is
      that the dynamic, competitive forces unleashed as a result of global market
      integration facilitates not only convergence in consumption habits (as is
      commonly assumed in the "Coca-Colonization" hypothesis), but adaptation to
      products targeted at different niche markets. This convergence-divergence duality
      raises the policy concern that globalization will exacerbate uneven dietary
      development between rich and poor. As high-income groups in developing countries
      accrue the benefits of a more dynamic marketplace, lower-income groups may well
      experience convergence towards poor quality obseogenic diets, as observed in
      western countries. Global economic policies concerning agriculture, trade,
      investment and marketing affect what the world eats. They are therefore also
      global food and health policies. Health policy makers should pay greater
      attention to these policies in order to address some of the structural causes of
      obesity and diet-related chronic diseases worldwide, especially among the groups
      of low socioeconomic status.

PMID- 16569240
TI  - Toward a treaty on safety and cost-effectiveness of pharmaceuticals and medical
      devices: enhancing an endangered global public good.
AB  - Expert evaluations of the safety, efficacy and cost-effectiveness of
      pharmaceutical and medical devices, prior to marketing approval or reimbursement
      listing, collectively represent a globally important public good. The scientific
      processes involved play a major role in protecting the public from product risks
      such as unintended or adverse events, sub-standard production and unnecessary
      burdens on individual and governmental healthcare budgets. Most States now have
      an increasing policy interest in this area, though institutional arrangements,
      particularly in the area of cost-effectiveness analysis of medical devices, are
      not uniformly advanced and are fragile in the face of opposing multinational
      industry pressure to recoup investment and maintain profit margins. This paper
      examines the possibility, in this context, of States commencing negotiations
      toward bilateral trade agreement provisions, and ultimately perhaps a
      multilateral Treaty, on safety, efficacy and cost-effectiveness analysis of
      pharmaceuticals and medical devices. Such obligations may robustly facilitate a
      conceptually interlinked, but endangered, global public good, without
      compromising the capacity of intellectual property laws to facilitate local
      product innovations.

PMID- 16569241
TI  - Ultrasound guided fine needle aspiration biopsy of parathyroid gland and lesions.
AB  - BACKGROUND: Parathyroid gland and their tumors comprise a small proportion of non
      palpable neck masses that are investigated by ultrasound (US) guided fine needle
      aspiration biopsy. We reviewed our institution's cases of US guided FNAB of
      parathyroid gland and their lesions to determine the role of cytology for the
      preoperative diagnosis of parathyroid gland and their lesions. METHOD: All cases
      of FNAB of parathyroid gland and lesions in the last 10 years were reviewed in
      detail with respect to clinical history and correlated with the histopathologic
      findings in available cases. The cytologic parameters that were evaluated
      included cellularity assessed semiquantitatively as scant, intermediate or
      abundant (<50, 51-500 or >500 cells), cellular distribution (loose clusters,
      single cells/naked nuclei, rounded clusters, two- and three-dimensional clusters,
      and presence of prominent vascular proliferation), cellular characteristics (cell
      size, nuclear shape, presence/absence of a nucleolus, degree of mitosis, amount
      of cytoplasm, and appearance of nuclear chromatin), and background (colloid-like
      material and macrophages). Immunostaining for parathyroid hormone (PTH) was
      performed on selected cases using either destained Pap smears or cell block
      sections. RESULTS: Twenty cases of US-guided FNAB of parathyroid glands and their
      lesions including 13 in the expected locations in the neck, 3 in intrathyroid
      region, 3 in thyroid bed, and 1 metastatic to liver were studied. Majority of the
      cases showed intermediate cellularity (51-500 cells) with round to oval cells
      that exhibited a stippled nuclear chromatin, without significant pleomorphism or
      mitotic activity. The cells were arranged in loose two dimensional groups with
      many single cells/naked nuclei around the groups. Occasionally macrophages and
      colloid like material was also encountered. There was no significant difference
      in the cytomorphologic features between normal gland, hyperplasia adenoma, or
      carcinoma. Immunocytochemical analysis for PHT was performed for 14 cases (6
      destained smears and 8 cell blocks) which showed distinct cytoplasmic positivity.
      CONCLUSION: US-guided FNAB is a useful test for confirming the diagnosis of not
      only clinically suspected parathyroid gland and lesions but also for detecting
      parathyroid glands in unexpected locations such as in thyroid bed or within the
      thyroid gland. Although there is significant overlap in the cytomorphologic
      features of cells derived from parathyroid and thyroid gland, the presence of
      stippled nuclear chromatin, prominent vascular proliferation with attached
      epithelial cells, and frequent occurrence of single cells/naked nuclei are useful
      clues that favor parathyroid origin. Distinction of the different parathyroid
      lesions including hyperplasia, adenoma, and carcinoma cannot be made solely on
      cytology. Immunostaining for PTH can be performed on destained Pap smears and
      cell block sections which can be valuable for confirming parathyroid origin of
      the cells.

PMID- 16569242
TI  - Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the
      locus assignment, narrowing of the critical region and mutation screening of
      three candidate genes.
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable
      disorder characterized by progressive degeneration of right ventricular
      myocardium, arrhythmias and an increased risk of sudden death at a young age. By
      linkage analysis, ARVC type 6 was previously mapped to a 10.6 cM region on
      chromosome 10p12-p14 in a large North American kindred. To date, the genetic
      defect that causes ARVC6 has not been identified. METHODS: We identified a South
      African family of 13 members with ARVC segregating as an autosomal dominant
      disorder. The diagnosis of ARVC was based on international diagnostic criteria.
      All available family members were genotyped with microsatellite markers at six
      known ARVC loci, and positional candidate gene screening was performed. RESULTS:
      Genetic linkage and haplotype analysis provided lod scores that are highly
      suggestive of linkage to the ARVC6 locus on chromosome 10p12-p14, and the
      narrowing of the critical region to approximately 2.9 Mb. Two positional
      candidate genes (ITG8 and FRMD4A) were screened in which defects could possibly
      disrupt cell-cell adhesion. A non-positional candidate gene with apoptosis
      inducing properties, LAMR1P6 (laminin receptor 1 pseudogene 6) was also screened.
      Direct sequencing of DNA from affected individuals failed to detect disease
      causing mutations in the exonic sequences of the three genes investigated.
      CONCLUSION: The narrowing of the ARVC6 critical region may facilitate progress
      towards the identification of the gene that is involved in ARVC. Identification
      of the causative genes for ARVC will contribute to the understanding of the
      pathogenesis and management of this poorly understood condition.

PMID- 16569243
TI  - Incorporating concepts of inequality and inequity into health benefits analysis.
AB  - BACKGROUND: Although environmental policy decisions are often based in part on
      both risk assessment information and environmental justice concerns, formalized
      approaches for addressing inequality or inequity when estimating the health
      benefits of pollution control have been lacking. Inequality indicators that
      fulfill basic axioms and agree with relevant definitions and concepts in health
      benefits analysis and environmental justice analysis can allow for quantitative
      examination of efficiency-equality tradeoffs in pollution control policies.
      METHODS: To develop appropriate inequality indicators for health benefits
      analysis, we provide relevant definitions from the fields of risk assessment and
      environmental justice and consider the implications. We evaluate axioms proposed
      in past studies of inequality indicators and develop additional axioms relevant
      to this context. We survey the literature on previous applications of inequality
      indicators and evaluate five candidate indicators in reference to our proposed
      axioms. We present an illustrative pollution control example to determine whether
      our selected indicators provide interpretable information. RESULTS AND
      CONCLUSIONS: We conclude that an inequality indicator for health benefits
      analysis should not decrease when risk is transferred from a low-risk to high
      risk person, and that it should decrease when risk is transferred from a high
      risk to low-risk person (Pigou-Dalton transfer principle), and that it should be
      able to have total inequality divided into its constituent parts (subgroup
      decomposability). We additionally propose that an ideal indicator should avoid
      value judgments about the relative importance of transfers at different
      percentiles of the risk distribution, incorporate health risk with evidence about
      differential susceptibility, include baseline distributions of risk, use
      appropriate geographic resolution and scope, and consider multiple competing
      policy alternatives. Given these criteria, we select the Atkinson index as the
      single indicator most appropriate for health benefits analysis, with other
      indicators useful for sensitivity analysis. Our illustrative pollution control
      example demonstrates how these indices can help a policy maker determine control
      strategies that are dominated from an efficiency and equality standpoint, those
      that are dominated for some but not all societal viewpoints on inequality
      averseness, and those that are on the optimal efficiency-equality frontier,
      allowing for more informed pollution control policies.

PMID- 16569244
TI  - Desmoid tumor in Gardner's Syndrome presented as acute abdomen.
AB  - BACKGROUND: Gardner's syndrome can occasionally be complicated with intra
      abdominal desmoid tumor. These tumors usually remain asymptomatic but can exhibit
      symptoms due to intestinal, vascular and ureteral compression and obstruction.
      CASE PRESENTATION: A rare case of a 41-year-old male patient with Gardner's
      syndrome complicated with intra-abdominal desmoid tumor, which first presented as
      acute abdomen, is presented. CONCLUSION: Extra-abdominal manifestations of
      Gardner's syndrome along with a palpable abdominal mass would raise suspicion for
      the presence of a desmoid tumor in the majority of cases. In life-threatening
      cases, surgical treatment should be considered as a palliative approach, though
      the extent of excision remains debatable.

PMID- 16569245
TI  - Oral mucosal melanoma: a malignant trap.
AB  - Oral mucosal melanomas are highly malignant tumors. The 'chameleonic'
      presentation of a mainly asymptomatic condition, the rarity of these lesions, the
      poor prognosis and the necessity of a highly specialized treatment are factors
      that should be seriously considered by the involved health provider. We present
      the case of a 75-year-old man who was referred to the Ear, Nose and Throat
      department. His symptoms were voice alteration and saliva drooling, progressively
      worsening during the last few weeks. The absence of pain was the reason for the
      delay of seeking medical care. The diagnosis was an oversized oral melanoma. This
      is an example of how the time of diagnosis and the evolution of a disease could
      be seriously influenced by patient's behavior. Melanomas arising from oral mucosa
      have poor prognosis unless they are discovered and treated early. The vigilance
      of the physicians is necessary to have success in this difficult task.

PMID- 16569246
TI  - Long-term effects of a single adult methamphetamine challenge: minor impact on
      dopamine fibre density in limbic brain areas of gerbils.
AB  - BACKGROUND: The aim of the study was to test long-term effects of (+)
      methamphetamine (MA) on the dopamine (DA) innervation in limbo-cortical regions
      of adult gerbils, in order to understand better the repair and neuroplasticity in
      disturbed limbic networks. METHODS: Male gerbils received a single high dose of
      either MA (25 mg/kg i.p.) or saline on postnatal day 180. On postnatal day 340
      the density of immunoreactive DA fibres and calbindin and parvalbumin cells was
      quantified in the right hemisphere. RESULTS: No effects were found in the
      prefrontal cortex, olfactory tubercle and amygdala, whereas the pharmacological
      impact induced a slight but significant DA hyperinnervation in the nucleus
      accumbens. The cell densities of calbindin (CB) and parvalbumin (PV) positive
      neurons were additionally tested in the nucleus accumbens, but no significant
      effects were found. The present results contrast with the previously published
      long-term effects of early postnatal MA treatment that lead to a restraint of the
      maturation of DA fibres in the nucleus accumbens and prefrontal cortex and a
      concomitant overshoot innervation in the amygdala. CONCLUSION: We conclude that
      the morphogenetic properties of MA change during maturation and aging of gerbils,
      which may be due to physiological alterations of maturing vs. mature DA neurons
      innervating subcortical and cortical limbic areas. Our findings, together with
      results from other long-term studies, suggest that immature limbic structures are
      more vulnerable to persistent effects of a single MA intoxication; this might be
      relevant for the assessment of drug experience in adults vs. adolescents, and
      drug prevention programs.

PMID- 16569248
TI  - The effects of early administration of atropine during dobutamine stress
      echocardiography: advantages and disadvantages of early dobutamine-atropine
      protocol.
AB  - BACKGROUND: The conventional dobutamine protocol for the investigation of induced
      myocardial ischemia is well established. Our objective was to evaluate the
      effects of early administration of atropine during the dobutamine stress
      echocardiogram, as compared to its conventional use. METHODS: One hundred and
      twenty-one patients were referred to the dobutamine stress echocardiogram, for
      the investigation of myocardial ischemia and the administration of atropine was
      randomized into three groups (A, B, C at 10, 20 and 40 mcg/kg/min of dobutamine,
      respectively). RESULTS: The mean level of the double product was significantly
      lower in the group C patients when compared to group B patients (p = 0.002). The
      mean test time (12.8 +/- 3.1 and 18.7 +/- 3.4 p= 0.0001) and the mean total dose
      of dobutamine (14 x 18 x 25 mg p = 0.008) were significantly higher in group C
      patients than in group A & B patients. The mean test time was reduced in 6
      minutes (31%) with the early administration of atropine in relation to the
      standard protocol. The atropine dose used in the different groups was similar.
      Complications were uniform in all cases. CONCLUSION: The early administration of
      atropine during the dobutamine-atropine stress echocardiography significantly
      reduces duration of the test and the dose of amine without increasing the number
      of complications, the total dose of atropine or the number of diagnostic tests.

PMID- 16569247
TI  - In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic
      acid in endometrial cancer.
AB  - Fenofibrate, an agonist of PPAR-alpha, in doses above 25 microM, inhibits
      proliferation and induces apoptosis in Ishikawa endometrial cancer cells. We show
      that these effects are potentiated by retinoic acid, an agonist of the retinoid-X
      receptor. DNA content analysis shows that G1/S phase progression through the cell
      cycle is inhibited. Independent Component Analysis of gene microarray experiments
      demonstrated downregulation of Cyclin D1 (CCND1) and associated changes in cell
      cycle gene expression. Expression of PPAR-alpha mRNA was reduced by >75% using
      RNA-interference but this resulted in only minor changes in biological effects. A
      nude mouse model of endometrial carcinoma was used to investigate the effect of
      fenofibrate in vivo but failed to show consistent inhibition of tumour growth.
      CONCLUSION: The combination of fenofibrate and retinoic acid is a potent
      inhibitor of Ishikawa endometrial cancer cell growth in vitro.

PMID- 16569250
TI  - Aiming at Tobacco Harm Reduction: a survey comparing smokers differing in
      readiness to quit.
AB  - BACKGROUND: Greece has the highest smoking rates (in the 15-nation bloc) in
      Europe. The purpose of this study was to investigate Greek smokers' intention and
      appraisal of capability to quit employing the theoretical frameworks of
      Decisional Balance (DB) and Cognitive Dissonance (CD). METHODS: A cross-sectional
      study including 401 Greek habitual smokers (205 men and 195 women), falling into
      four groups according to their intention and self-appraised capability to quit
      smoking was carried out. Participants completed a questionnaire recording their
      attitude towards smoking, intention and self appraised capability to quit
      smoking, socio-demographic information, as well as a DB and a CD scale. RESULTS:
      The most numerous group of smokers (38%) consisted of those who neither intended
      nor felt capable to quit and these smokers perceived more benefits of smoking
      than negatives. DB changed gradually according to smokers' "readiness" to quit:
      the more ready they felt to quit the less the pros of smoking outnumbered the
      cons. Regarding relief of CD, smokers who intended but did not feel capable to
      quit employed more "excuses" compared to those who felt capable. Additionally
      smokers with a past history of unsuccessful quit attempts employed fewer
      "excuses" even though they were more frequently found among those who intended
      but did not feel capable to quit. CONCLUSION: Findings provide support for the DB
      theory. On the other hand, "excuses" do not appear to be extensively employed to
      reduce the conflict between smoking and concern for health. There is much
      heterogeneity regarding smokers' intention and appraised capability to quit,
      reflecting theoretical and methodological problems with the distinction among
      stages of change. Harm reduction programs and interventions designed to increase
      the implementation of smoking cessation should take into account the detrimental
      effect of past unsuccessful quit attempts.

PMID- 16569249
TI  - Impact of treatment policies on patient outcomes and resource utilization in
      acute cholecystitis in Japanese hospitals.
AB  - BACKGROUND: Although currently available evidence predominantly recommends early
      laparoscopic cholecystectomy (LC) for the treatment of acute cholecystitis, this
      strategy has not been widely adopted in Japan. Herein, we describe a hospital
      based study of patients with acute cholecystitis in 9 Japanese teaching hospitals
      in order to evaluate the impact of different institutional strategies in treating
      acute cholecystitis on overall patient outcomes and medical resource utilization.
      METHODS: From an administrative database and chart review, we identified 228
      patients diagnosed with acute cholecystitis who underwent cholecystectomy between
      April 2001 and June 2003. In order to examine the relationship between hospitals'
      propensity to perform LC and patient outcomes and/or medical resource
      utilization, we divided the hospitals into three groups according to the observed
      to expected ratio of performing LC (LC propensity), and compared the
      postoperative complication rate, length of hospitalization (LOS), and medical
      charges. RESULTS: No hospital adopted the policy of early surgery, and the mean
      overall LOS among the subjects was 30.9 days. The use of laparoscopic surgery
      varied widely across the hospitals; the adjusted rates of LC to total
      cholecystectomies ranged from 9.5% to 77%. Although intra-operative complication
      rate was significantly higher among patients whom LC was initially attempted when
      compared to those whom OC was initially attempted (9.7% vs. 0%), there was no
      significant association between LC propensity and postoperative complication
      rates. Although the postoperative time to oral intake and postoperative LOS was
      significantly shorter in hospitals with high use of LC, the overall LOS did not
      differ among hospital groups with different LC propensities. Medical charges were
      not associated with LC propensity. CONCLUSION: Under the prevailing policy of
      delayed surgery, in terms of the postoperative complication rate and medical
      resource utilization, our study did not show the superiority of LC in treating
      acute cholecystitis patients. The timing of surgery and discharge was mainly
      determined by the institutional policy in Japan, rather than by the clinical
      course of the patient; however, considering the substantially less postoperative
      pain and shorter recovery time of LC compared to OC, LC should be actively
      applied for the treatment of acute cholecystitis. If the policy of early surgery
      were universally applied, the advantage of LC over OC may be more clearly
      demonstrated.

PMID- 16569251
TI  - Single nucleotide polymorphisms of the APC gene and colorectal cancer risk: a
      case-control study in Taiwan.
AB  - BACKGROUND: Colorectal cancer (CRC), which has become especially prevalent in
      developed countries, is currently the third highest cause of cancer mortality in
      Taiwan. Mutation of the adenomatous polyposis coli (APC) gene, a tumour
      suppressor, is thought to be an early event in colorectal tumourigenesis. To
      date, however, no large-scale screening for APC gene variants in Chinese subjects
      has been performed. The present study was undertaken to identify APC gene
      variants that are significantly associated with the occurrence of CRC in
      Taiwanese subjects. METHODS: In order to compare the genotype distribution of
      variant sites, the full-length APC genes of 74 healthy individuals and 80 CRC
      patients were sequenced. RESULTS: Among the 154 Taiwanese subjects examined in
      this study, three new mutations, but no previously reported mutations, were
      found. One deletion at codon 460 leading to a frameshift and two missense
      mutations resulting in p.V1125A and p.S1126R substitutions were identified.
      Additionally, three high risk genotypes associated with three single nucleotide
      polymorphisms and one low risk genotype at codon 1822 were identified.
      CONCLUSION: The findings of this case-control study are consistent with the
      proposal that Taiwanese subjects differ from other subjects with respect to
      phenotypic presentation of APC and CRC risk.

PMID- 16569252
TI  - Putting the genie back in the bottle? Availability and presentation of oral
      artemisinin compounds at retail pharmacies in urban Dar-es-Salaam.
AB  - BACKGROUND: Recently global health advocates have called for the introduction of
      artemisinin-containing antimalarial combination therapies to help curb the impact
      of drug-resistant malaria in Africa. Retail trade in artemisinin monotherapies
      could undermine efforts to restrict this class of medicines to more theoretically
      sound combination treatments. METHODS: This paper describes a systematic search
      for artemisinin-containing products at a random sample of licensed pharmacies in
      Dar-es-Salaam, Tanzania in July 2005. RESULTS: Nineteen different artemisinin
      containing oral pharmaceutical products, including one co-formulated product, one
      co-packaged product, and 17 monotherapies were identified. All but one of the
      products were legally registered and samples of each product were obtained
      without a prescription. Packaging and labeling of the products seldom included
      local language or illustrated instructions for low-literate clients. Packaging
      and inserts compared reasonably well with standards recommended by the national
      regulatory authority with some important exceptions. Dosing instructions were
      inconsistent, and most recommended inadequate doses based on international
      standards. None of the monotherapy products mentioned potential benefits of
      combining the treatment with another antimalarial drug. CONCLUSION: The findings
      confirm the widespread availability of artemisinin monotherapies that led the
      World Health Organization to call for the voluntary withdrawal of these drugs in
      malaria-endemic countries. As the global public health community gathers
      resources to deploy artemisinin-containing combination therapies in Africa,
      planners should be mindful that these drugs will coexist with artemisinin
      monotherapies in an already well-established market place. In particular,
      regulatory authorities should be incorporated urgently into the process of
      planning for rational deployment of artemisinin-containing antimalarial
      combination therapies.

PMID- 16569253
TI  - Energy expenditure of acutely ill hospitalised patients.
AB  - OBJECTIVE: To measure energy expenditure of acutely ill elderly patients in
      hospital and following discharge in the community. DESIGN: Sixty-three
      consecutive hospitalised acutely ill elderly patients were recruited. Eight
      patients were studied to assess the reliability of the Delta Tract Machine as a
      measure of energy expenditure; 35 patients had their energy expenditure studied
      in hospital on two occasions and 20 patients had their energy expenditure
      measured in hospital and at 6 weeks in the community RESULTS: Men had higher
      basal energy expenditure (BMR) values compared to women however the difference
      was not statistically significant [Men, mean (SD) 1405 (321) Kcal, women 1238
      (322) kcal; mean difference (95% CI) 166 kcal (-17 to 531), p = 0.075]. After
      adjusting for age, gender and body mass index both medication and C-reactive
      protein (CRP), concentrations showed significant correlation with measured energy
      expenditure in hospital, (r = -0.36, "p < 0.05"; r = -0.29, "p < 0.05"
      respectively). However, in a multivariate analysis for all 63 subjects combined
      CRP explained most of the variance in BMR in hospital. The Harris Benedict
      equation predicted within +/- 10% measured BMR in only 47% of individuals in
      hospital. CONCLUSION: Tissue inflammation and medications were associated with
      change in measured energy expenditure in acutely ill patients.

PMID- 16569254
TI  - A comparison of continuous and bi-level positive airway pressure non-invasive
      ventilation in patients with acute cardiogenic pulmonary oedema: a meta-analysis.
AB  - INTRODUCTION: We conducted the present study to investigate the potential
      beneficial and adverse effects of continuous positive airway pressure (CPAP)
      compared with bi-level positive airway pressure (BiPAP) noninvasive ventilation
      in patients with cardiogenic pulmonary oedema. METHOD: We included randomized
      controlled studies comparing CPAP and BiPAP treatment in patients with
      cardiogenic pulmonary oedema from the Cochrane Controlled Trials Register (2005
      issue 3), and EMBASE and MEDLINE databases (1966 to 1 December 2005), without
      language restriction. Two reviewers reviewed the quality of the studies and
      independently performed data extraction. RESULTS: Seven randomized controlled
      studies, including a total of 290 patients with cardiogenic pulmonary oedema,
      were considered. The hospital mortality (relative risk [RR] 0.76, 95% confidence
      interval [CI] 0.32-1.78; P = 0.52; I2 = 0%) and risk for requiring invasive
      ventilation (RR 0.80, 95% CI 0.33-1.94; P = 0.62; I2 = 0%) were not significantly
      different between patients treated with CPAP and those treated with BiPAP.
      Stratifying studies that used either fixed or titrated pressure during BiPAP
      treatment and studies involving patients with or without hypercapnia did not
      change the results. The duration of noninvasive ventilation required until the
      pulmonary oedema resolved (weighted mean difference [WMD] in hours = 3.65, 95% CI
      -12.12 to +19.43; P = 0.65, I2 = 0%) and length of hospital stay (WMD in days = 
      0.04, 95% CI -2.57 to +2.48; P = 0.97, I2 = 0%) were also not significantly
      different between the two groups. Based on the limited data available, there was
      an insignificant trend toward an increase in new onset acute myocardial
      infarction in patients treated with BiPAP (RR 2.10, 95% CI 0.91-4.84; P = 0.08;
      I2 = 25.3%). CONCLUSION: BiPAP does not offer any significant clinical benefits
      over CPAP in patients with acute cardiogenic pulmonary oedema. Until a large
      randomized controlled trial shows significant clinical benefit and cost
      effectiveness of BiPAP versus CPAP in patients with acute cardiogenic pulmonary
      oedema, the choice of modality will depend mainly on the equipment available.

PMID- 16569255
TI  - Decompressive laparotomy for abdominal compartment syndrome--a critical analysis.
AB  - INTRODUCTION: Abdominal compartment syndrome (ACS) is increasingly recognized in
      critically ill patients, and the deleterious effects of increased intraabdominal
      pressure (IAP) are well documented. Surgical decompression through a midline
      laparotomy or decompressive laparotomy remains the sole definite therapy for ACS,
      but the effect of decompressive laparotomy has not been studied in large patient
      series. METHODS: We reviewed English literature from 1972 to 2004 for studies
      reporting the effects of decompressive laparotomy in patients with ACS. The
      effect of decompressive laparotomy on IAP, patient outcome and physiology were
      analysed. RESULTS: Eighteen studies including 250 patients who underwent
      decompressive laparotomy could be included in the analysis. IAP was significantly
      lower after decompression (15.5 mmHg versus 34.6 mmHg before, p < 0.001), but
      intraabdominal hypertension persisted in the majority of the patients. Mortality
      in the whole group was 49.2% (123/250). The effect of decompressive laparotomy on
      organ function was not uniform, and in some studies no effect on organ function
      was found. Increased PaO2/FIO2 ratio (PaO2 = partial pressure of oxygen in
      arterial blood, FiO2 = fraction of inspired oxygen) and urinary output were the
      most pronounced effects of decompressive laparotomy. CONCLUSION: The effects of
      decompressive laparotomy have been poorly investigated, and only a small number
      of studies report its effect on parameters of organ function. Although IAP is
      consistently lower after decompression, mortality remains considerable.
      Recuperation of organ dysfunction after decompressive laparotomy for ACS is
      variable.

PMID- 16569257
TI  - Magnetic resonance imaging in psoriatic arthritis: a review of the literature.
AB  - Psoriatic arthritis is a diverse condition that may be characterized by
      peripheral inflammatory arthritis, axial involvement, dactylitis and enthesitis.
      Magnetic resonance imaging (MRI) allows visualization of soft tissue, articular
      and entheseal lesions, and provides a unique picture of the disease process that
      cannot be gained using other imaging modalities. This review focuses on the
      literature on MRI in psoriatic arthritis published from 1996 to July 2005. The
      MRI features discussed include synovitis, tendonitis, dactylitis, bone oedema,
      bone erosions, soft tissue oedema, spondylitis/sacroiliitis and subclinical
      arthropathy. Comparisons have been drawn with the more extensive literature
      describing the MRI features of rheumatoid arthritis and ankylosing spondylitis.

PMID- 16569256
TI  - Most recent developments in strategies to reduce the progression of structural
      changes in osteoarthritis: today and tomorrow.
AB  - Osteoarthritis (OA), the most common of all arthritic conditions, is a social and
      financial burden to all nations. The most recent research has significantly
      advanced our understanding of the cause of OA and risk factors associated with
      it. These findings have provided useful information that has helped in the daily
      management of patients with OA. Some preventative measures and a number of
      therapeutic agents and drugs are available, which may help to reduce the
      progression of OA in certain patients. Moreover, the most recent progress in
      research has significantly enhanced our knowledge of the factors involved in the
      development of the disease and of the mechanisms responsible for its progression.
      This has allowed identification of several new therapeutic targets in a number of
      pathophysiological pathways. Consequently, the field is opening up to a new era
      in which drugs and agents that can specifically block important mechanisms
      responsible for the structural changes that occur in OA can be brought into
      development and eventually into clinical trials.

PMID- 16569259
TI  - Is it time for implementation of tight glycaemia control by intensive insulin
      therapy in every ICU?
AB  - The second study on tight glycaemia control by intensive insulin therapy (IIT)
      confirmed in medical intensive care unit patients the decrease in hospital
      mortality reported by the same team in the first IIT trial in surgical patients.
      However, methodological concerns, the high rate of hypoglycaemia in spite of the
      infusion of large doses of parenteral glucose and the frequent use of steroids
      presently preclude considering these results as recommendations in other
      intensive care units, but rather argue for the need for large-scale assessment of
      the IIT approach by multi-centre studies to confirm the efficacy and safety of
      this therapeutic modality.

PMID- 16569258
TI  - Anopheles gambiae genome reannotation through synthesis of ab initio and
      comparative gene prediction algorithms.
AB  - BACKGROUND: Complete genome annotation is a necessary tool as Anopheles gambiae
      researchers probe the biology of this potent malaria vector. RESULTS: We
      reannotate the A. gambiae genome by synthesizing comparative and ab initio sets
      of predicted coding sequences (CDSs) into a single set using an exon-gene-union
      algorithm followed by an open-reading-frame-selection algorithm. The reannotation
      predicts 20,970 CDSs supported by at least two lines of evidence, and it lowers
      the proportion of CDSs lacking start and/or stop codons to only approximately 4%.
      The reannotated CDS set includes a set of 4,681 novel CDSs not represented in the
      Ensembl annotation but with EST support, and another set of 4,031 Ensembl
      supported genes that undergo major structural and, therefore, probably functional
      changes in the reannotated set. The quality and accuracy of the reannotation was
      assessed by comparison with end sequences from 20,249 full-length cDNA clones,
      and evaluation of mass spectrometry peptide hit rates from an A. gambiae shotgun
      proteomic dataset confirms that the reannotated CDSs offer a high quality protein
      database for proteomics. We provide a functional proteomics annotation,
      ReAnoXcel, obtained by analysis of the new CDSs through the AnoXcel pipeline,
      which allows functional comparisons of the CDS sets within the same bioinformatic
      platform. CDS data are available for download. CONCLUSION: Comprehensive A.
      gambiae genome reannotation is achieved through a combination of comparative and
      ab initio gene prediction algorithms.

PMID- 16569261
TI  - Combination therapy versus monotherapy: a randomised pilot study on the evolution
      of inflammatory parameters after ventilator associated pneumonia
      [ISRCTN31976779].
AB  - INTRODUCTION: Combination antibiotic therapy for ventilator associated pneumonia
      (VAP) is often used to broaden the spectrum of activity of empirical treatment.
      The relevance of such synergy is commonly supposed but poorly supported. The aim
      of the present study was to compare the clinical outcome and the course of
      biological variables in patients treated for a VAP, using a monotherapy with a
      beta-lactam versus a combination therapy. METHODS: Patients with VAP were
      prospectively randomised to receive either cefepime alone or cefepime in
      association with amikacin or levofloxacin. Clinical and inflammatory parameters
      were measured on the day of inclusion and thereafter. RESULTS: Seventy-four
      mechanically ventilated patients meeting clinical criteria for VAP were enrolled
      in the study. VAP was microbiologically confirmed in 59 patients (84%). Patients
      were randomised to receive cefepime (C group, 20 patients), cefepime with
      amikacin (C-A group, 19 patients) or cefepime with levofloxacin (C-L group, 20
      patients). No significant difference was observed regarding the time course of
      temperature, leukocytosis or C-reactive protein level. There were no differences
      between length of stay in the intensive care unit after infection, nor in
      ventilator free days within 28 days after infection. No difference in mortality
      was observed. CONCLUSION: Antibiotic combination using a fourth generation
      cephalosporin with either an aminoside or a fluoroquinolone is not associated
      with a clinical or biological benefit when compared to cephalosporin monotherapy
      against common susceptible pathogens causing VAP.

PMID- 16569260
TI  - Growth of a human mammary tumor cell line is blocked by galangin, a naturally
      occurring bioflavonoid, and is accompanied by down-regulation of cyclins D3, E,
      and A.
AB  - INTRODUCTION: This study was designed to determine if and how a non-toxic,
      naturally occurring bioflavonoid, galangin, affects proliferation of human
      mammary tumor cells. Our previous studies demonstrated that, in other cell types,
      galangin is a potent inhibitor of the aryl hydrocarbon receptor (AhR), an
      environmental carcinogen-responsive transcription factor implicated in mammary
      tumor initiation and growth control. Because some current breast cancer
      therapeutics are ineffective in estrogen receptor (ER) negative tumors and since
      the AhR may be involved in breast cancer proliferation, the effects of galangin
      on the proliferation of an ER-, AhRhigh line, Hs578T, were studied. METHODS: AhR
      expression and function in the presence or absence of galangin, a second AhR
      inhibitor, alpha-naphthoflavone (alpha-NF), an AhR agonist, indole-3-carbinol,
      and a transfected AhR repressor-encoding plasmid (FhAhRR) were studied in Hs578T
      cells by western blotting for nuclear (for instance, constitutively activated)
      AhR and by transfection of an AhR-driven reporter construct, pGudLuc. The effects
      of these agents on cell proliferation were studied by 3H-thymidine incorporation
      and by flow cytometry. The effects on cyclins implicated in mammary tumorigenesis
      were evaluated by western blotting. RESULTS: Hs578T cells were shown to express
      high levels of constitutively active AhR. Constitutive and environmental chemical
      induced AhR activity was profoundly suppressed by galangin as was cell
      proliferation. However, the failure of alpha-NF or FhAhRR transfection to block
      proliferation indicated that galangin-mediated AhR inhibition was either
      insufficient or unrelated to its ability to significantly block cell
      proliferation at therapeutically relevant doses (IC50 = 11 microM). Galangin
      inhibited transition of cells from the G0/G1 to the S phases of cell growth,
      likely through the nearly total elimination of cyclin D3. Expression of cyclins A
      and E was also suppressed. CONCLUSION: Galangin is a strong inhibitor of Hs578T
      cell proliferation that likely mediates this effect through a relatively unique
      mechanism, suppression of cyclin D3, and not through the AhR. The results suggest
      that this non-toxic bioflavonoid may be useful as a chemotherapeutic,
      particularly in combination with agents that target other components of the tumor
      cell cycle and in situations where estrogen receptor-specific therapeutics are
      ineffective.

PMID- 16569264
TI  - Mining the HapMap to dissect complex traits.

PMID- 16569262
TI  - Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive
      protein in community-acquired infections and sepsis: a prospective study.
AB  - INTRODUCTION: Clinicians are in need of better diagnostic markers in diagnosing
      infections and sepsis. We studied the ability of procalcitonin,
      lipopolysaccharide-binding protein, IL-6 and C-reactive protein to identify
      patients with infection and sepsis. METHODS: Plasma and serum samples were
      obtained on admission from patients with suspected community-acquired infections
      and sepsis. Procalcitonin was measured with a time-resolved amplified cryptate
      emission technology assay. Lipopolysaccharide-binding protein and IL-6 were
      measured with a chemiluminescent immunometric assay. RESULTS: Of 194 included
      patients, 106 had either infection without systemic inflammatory response
      syndrome or sepsis. Infected patients had significantly elevated levels of
      procalcitonin, lipopolysaccharide-binding protein, C-reactive protein and IL-6
      compared with noninfected patients (P < 0.001). In a receiver-operating
      characteristic curve analysis, C-reactive protein and IL-6 performed best in
      distinguishing between noninfected and infected patients, with an area under the
      curve larger than 0.82 (P < 0.05). IL-6, lipopolysaccharide-binding protein and C
      reactive protein performed best in distinguishing between systemic inflammatory
      response syndrome and sepsis, with an area under the curve larger than 0.84 (P <
      0.01). Procalcitonin performed best in distinguishing between sepsis and severe
      sepsis, with an area under the curve of 0.74 (P < 0.01). CONCLUSION: C-reactive
      protein, IL-6 and lipopolysaccharide-binding protein appear to be superior to
      procalcitonin as diagnostic markers for infection and sepsis in patients admitted
      to a Department of Internal Medicine. Procalcitonin appears to be superior as a
      severity marker.

PMID- 16569265
TI  - A cornucopia of genomes.

PMID- 16569263
TI  - Immune complexes from rheumatoid arthritis synovial fluid induce FcgammaRIIa
      dependent and rheumatoid factor correlated production of tumour necrosis factor
      alpha by peripheral blood mononuclear cells.
AB  - Immune complexes (ICs) can induce production of cytokines by peripheral blood
      mononuclear cells via Fc receptors. Rheumatoid factor (RF) develop in response to
      ICs in many clinical and experimental settings. We investigated whether and how
      polyethylene glycol (PEG) precipitated ICs from rheumatoid arthritis (RA) sera
      and synovial fluid (SF) can influence cytokine production by peripheral blood
      mononuclear cells. We also examined the relationship between RF and IC induced
      cytokine production. Parallel sera and SF from 47 RA patients and sera from 15
      healthy control individuals were PEG precipitated. The precipitates were added to
      serum-free peripheral blood mononuclear cell cultures and tumour necrosis factor
      (TNF)-alpha levels were measured after 20 hours. In separate cell culture
      experiments FcgammaRIIa and FcgammaRIII were blocked and monocytes were depleted
      or enriched. RF in serum was determined by nephelometry, and IgG levels in
      precipitates and anti-cyclic citrullinated peptide antibodies in serum were
      measured using ELISA. Clinical data were collected from the patients' charts. In
      two separate investigations, we demonstrated a correlation between RF, PEG
      precipitated IgG levels and induction of the proinflammatory cytokine TNF-alpha
      by PEG-precipitated SF ICs. No such correlation was found for serum ICs. TNF
      alpha levels induced by SF precipitates, but not serum precipitates, correlated
      with the number of swollen and tender joints. Monocytes/macrophages were shown to
      be the main responder cells, and blockade of FcgammaRIIa, but not blockade of
      FcgammaRIII, inhibited TNF-alpha production in cultures stimulated with
      precipitated ICs. Anti-cyclic citrullinated peptide correlated with RF but
      exhibited no association with IgG content in PEG precipitates or with precipitate
      induced TNF-alpha levels. These findings support the hypothesis that SF ICs and
      correlated RF production are directly linked to cytokine-dependent inflammation
      in RA. Suppression of monocytes/macrophages in RA joints or blockade of the
      primate-specific activating FcgammaRIIa receptor might be ways to reduce IC
      induced TNF-alpha production in the joints of seropositive RA patients.

PMID- 16569266
TI  - Abnormally increased power of breathing as a complication of closed endotracheal
      suction catheter systems.

PMID- 16569267
TI  - Commercial watercress as an emerging source of fascioliasis in Northern France in
      2002: results from an outbreak investigation.
AB  - In April 2002, five cases of fascioliasis were diagnosed in Tourcoing. A case
      finding and a case-control study were carried out to identify the source of the
      outbreak and take appropriate control measures. Eighteen cases were identified
      through the medical laboratories carrying out serology for fascioliasis. Fourteen
      cases and 23 controls, identified by the physicians of the cases, were
      interviewed on symptoms of the disease and their consumption of uncooked plants.
      Cases were more likely than controls to have eaten commercialized raw watercress
      (OR 86.7, P < 0.001) and 13 (93%) of the cases reported its consumption. A single
      producer common to all cases was identified. The inspection of his watercress
      beds showed a lack of protection against Lymnaea truncatula. This outbreak of
      fascioliasis due to commercialized watercress indicates that actual sanitary
      regulations do not allow for the efficient prevention of infestation of
      watercress production in France.

PMID- 16569268
TI  - Continuing Mycobacterium bovis transmission from animals to humans in New
      Zealand.
AB  - New Zealand has a large reservoir of Mycobacterium bovis infection in wild and
      farmed animals. This study aimed to assess the extent of human infection with
      this organism and the potential contribution of these animal sources. Combined
      epidemiological and laboratory investigation of human tuberculosis cases over the
      period 1995-2002 showed that M. bovis accounted for 2.7% (54/1997) of laboratory
      confirmed human tuberculosis cases, a rate of 0.2/100,000 population. M. bovis
      isolates from humans (23) were typed using restriction endonuclease analysis
      (REA) and compared with isolates from wild and domestic animals (2600). Fourteen
      (61%) of the human isolates had REA patterns that were identical to patterns for
      isolates from cattle, deer, possums, ferrets, pigs, and occasionally cats. These
      results suggest a low level of ongoing M. bovis transmission from animal
      reservoirs to humans in New Zealand.

PMID- 16569269
TI  - Prolonged outbreak of giardiasis with two modes of transmission.
AB  - Large outbreaks of giardiasis caused by person-to-person transmission, or a
      combination of transmission routes, have not previously been reported. A large,
      prolonged giardiasis outbreak affected families belonging to a country club in a
      suburb of Boston, Massachusetts, during June-December 2003. We conducted a
      retrospective cohort study to determine the source of this outbreak. Giardiasis
      compatible illness was experienced by 149 (25%) respondents to a questionnaire,
      and was laboratory confirmed in 97 (65%) of these cases. Of the 30 primary cases,
      exposure to the children's pool at the country club was significantly associated
      with illness (risk ratio 3.3, 95% confidence interval 1.7-6.5). In addition, 105
      secondary cases probably resulted from person-to-person spread; 14 cases did not
      report an onset date. This outbreak illustrates the potential for Giardia to
      spread through multiple modes of transmission, with a common-source outbreak
      caused by exposure to a contaminated water source resulting in subsequent
      prolonged propagation through person-to-person transmission in the community.
      This capacity for a common-source outbreak to continue propagation through
      secondary person-to-person spread has been reported with Shigella and
      Cryptosporidium and may also be a feature of other enteric pathogens having low
      infectious doses.

PMID- 16569270
TI  - Molecular epidemiology of norovirus strains circulating in Ireland from 2003 to
      2004.
AB  - Since 2002, the burden of norovirus (NoV) infection in Ireland has increased.
      Outbreaks in institutional settings are the most common causing widespread
      disruption to health service delivery. This is the first national study of NoV in
      the Republic of Ireland and its aim was to identify the major NoV strains
      circulating in Ireland over a 13-month period between November 2003 and November
      2004, inclusive. A prospective study screened faecal samples (n = 478) for NoV
      RNA. Positive samples (n = 116) were further analysed by a second PCR, targeted
      to the orf1/orf2 junction of the virus. Phylogenetic analysis was based on
      sequence alignments of this domain. GII/4 viruses represented 92.2% of sequences,
      2.7% were GII/2, GII/3 and GGIIB cluster-like strains. The remaining 5.2% were of
      GI origin. NoV was detectable throughout the study period, although two peaks of
      infection were observed. The majority of infections were caused by a range of
      closely related GII/4 NoV strains.

PMID- 16569271
TI  - Prevalence of sputum smear-positive tuberculosis in a rural area in Bangladesh.
AB  - The objective of the study was to determine the prevalence of smear-positive
      tuberculosis (TB) in a rural area in Bangladesh at Matlab. A TB surveillance
      system was established among 106,000 people in rural Bangladesh at Matlab.
      Trained field workers interviewed all persons aged > or = 15 years to detect
      suspected cases of TB (cough > 21 days) and sputum specimens of suspected cases
      were examined for acid-fast bacilli (AFB). Of 59,395 persons interviewed, 4235
      (7.1%) had a cough for > 21 days. Sputum specimens were examined for AFB from
      3834 persons, 52 (1.4%) of them were positive for AFB. The prevalence of chronic
      cough and sputum positivity were significantly higher among males compared to
      females (P < 0.001). The population-based prevalence rate of smear-positive TB
      cases was 95/100,000 among persons aged > or = 15 years. Cases of TB clustered
      geographically (relative risk 5.53, 95% CI 3.19-9.59). The high burden of TB
      among rural population warrants appropriate measures to control TB in Bangladesh.
      The higher prevalence of persistent cough and AFB-positive sputum among males
      need further exploration. Factors responsible for higher prevalence of TB in
      clusters should be investigated.

PMID- 16569272
TI  - Does dog or cat ownership lead to increased gastroenteritis in young children in
      South Australia?
AB  - The aim of this study was to investigate the relationship between dog and cat
      ownership and gastroenteritis in young children. A diary study of 965 children
      aged 4-6 years living in rural or semi-rural South Australia was undertaken. Data
      were collected on pet ownership, drinking water and other risk factors for
      gastroenteritis. Overall 89% of households had pets and dog ownership was more
      common than cat ownership. The multivariable models for gastroenteritis and pet
      ownership indicated that living in a household with a dog or cat was associated
      with a reduced risk of gastroenteritis (adj. OR 0.71, 95% CI 0.55-0.92; OR 0.70,
      % CI 0.51-0.97 respectively). This paper adds to the evidence that pets are not a
      major source of gastroenteritis in the home and lends support to the health
      benefits of pet ownership. However, this must be weighed against the potential
      negative consequences, such as dog bites, particularly for this age group.

PMID- 16569273
TI  - How safe is safer sex? High levels of HSV-1 and HSV-2 in female sex workers in
      London.
AB  - Female sex workers in Europe have low levels of sexually transmitted infections,
      attributable to condom use. The aim of this paper is to describe the
      seroepidemiology of HSV-1 and HSV-2 in female sex workers in London by using a 15
      year prospective study of 453 sex workers. The seroprevalence of HSV-1 was 74.4%
      and independently associated with birth in a 'transitional country' (OR 5.4, 95%
      CI 1.61-18.20). The seroprevalence of HSV-2 was 60% and declined over time; it
      was also independently associated with time in sex work (OR 2.12, 95% CI 1.23
      3.65) and birth in a 'developing country' (OR 2.95, 95% CI 1.34-6.48). We show
      that a cohort of sex workers with extensive condom use and little known sexually
      transmitted infection have high levels of HSV-1 and HSV-2 infection, suggesting
      that condoms may not be universally protective. Sex workers are candidates for
      HSV vaccine efficacy or intervention studies.

PMID- 16569274
TI  - Effects of prepartum milking on postpartum reproduction, udder health and
      production performance in first-calf dairy heifers.
AB  - Postpartum production performance of dairy heifers may be enhanced by prepartum
      milking by alleviating the stress of the periparturient period. The objective of
      this study was to determine the impact of prepartum milking of dairy heifers on
      postpartum reproduction, udder health, milk production and other associated
      production characteristics. Pregnant heifers (Holstein, n=21; Jersey n=10) were
      assigned to either a prepartum milked (premilked, n=15) or control (n=16) group.
      Premilked heifers were milked twice daily starting 3 weeks prior to anticipated
      calving dates, and milk yield recorded at each milking. All heifers were
      evaluated on days 21, 14 and 7 before calving, and udder oedema scores and milk
      conductivity readings were recorded. Following calving, measurements were taken
      twice weekly to assess udder oedema, milk conductivity (indicative of udder
      infection), and reproductive health, which included palpation for uterine tone
      and uterine position, vaginal electrical impedance (VEI) and the quantification
      of cross-sectional area of the uterine horns (uterine difference) by transrectal
      ultrasonography. Uterine tone, uterine position, uterine difference, and VEI did
      not differ (P>0.10) with treatment. Overall, up to week six inclusive, postpartum
      premilked heifers had lower (P<0.01) udder oedema scores than control heifers and
      up to week five inclusive, had lower (P<0.01) milk conductivity readings
      (indicative of fewer incidences of udder infections) than control heifers. The
      premilked heifers of both breeds produced more milk (P<0.01) at calving and more
      milk overall from calving to day 60 postpartum than the control heifers. In
      summary, udder health and milk production were improved post calving in premilked
      heifers compared with controls. However, no overt differences in reproductive
      characteristics were observed between the premilked and control heifers.

PMID- 16569275
TI  - Economic impacts of reduced milk production associated with papillomatous digital
      dermatitis in dairy cows in the USA.
AB  - The goal of this study was to measure the economic impacts of reduced milk
      production associated with papillomatous digital dermatitis (PDD) in dairy cows
      in the USA, and of specific risk factors for PDD, in 1996. The method applied was
      an economic-welfare analysis of producer and consumer surplus, with the GUM
      Workbench used to analyse uncertainties in the measurements. Reduced milk
      production associated with PDD was found to reduce consumer surplus by Dollars
      750 million +/- Dollars 580 million, and to increase the economic surplus of
      producers by Dollars 560 million +/- Dollars 470 million, with a net economic
      loss of Dollars 190 million +/- Dollars 130 million. An examination of the
      economic effects of specific epidemiologic risk factors for PDD showed that
      having dairy cows that were not born on the operation had important economic
      consequences associated with the disease, as did the type of land to which dairy
      cows had access during the winter months and the type of flooring on which cows
      walked. Washing hoof-trimming equipment between cows was an important biosecurity
      measure that was associated with reduced PDD. The epidemiologic model used also
      implicated hoof trimmers who trimmed cattle hooves on other operations as having
      an important economic impact associated with this disease, although this finding
      may have been erroneous.

PMID- 16569276
TI  - Evaluation of microbial diversity during the manufacture of Fior di Latte di
      Agerola, a traditional raw milk pasta-filata cheese of the Naples area.
AB  - Microbial diversity of the raw milk for the production of Fior di Latte di
      Agerola and its changes during cheesemaking were studied. Viable counts showed
      that at the end of curd ripening, loads of lactic acid bacteria, both mesophilic
      and thermophilic rods and cocci, higher than those commonly evidenced in similar
      cheeses produced by using natural or commercial starters, were detected.
      Identification of 272 isolates, supported by molecular diagnostic aids, evidenced
      representative cultures of a high number of bacterial taxa of interest as
      participating in the process, although most of the isolates belonged to
      Lactococcus lactis and Lactobacillus helveticus species. RAPD-PCR and REA-PFGE
      biotyping were performed for the isolates of the above species and it was shown
      that most of the strains isolated from the raw milk occurred during the whole
      cheesemaking process, and an active role of these strains in the fermentation was
      supposed. The results offer further proof of the importance of the raw milk as
      source of technologically interesting strains of lactic acid bacteria capable of
      driving the fermentation of traditional cheeses.

PMID- 16569277
TI  - Biosensor assay for determination of haptoglobin in bovine milk.
AB  - Despite more than 30 years of research into mastitis diagnostics, there are few
      alternatives to the somatic cell count (SCC) in practical use for identification
      of cows with subclinical mastitis. Mastitis is not only an animal welfare
      problem, but also affects the yield, composition and technological properties of
      milk. Hence, dairy cooperatives give farmers a premium quality payment to
      encourage low SCC although there is no clear scientific data defining the level
      of SCC in bulk tank milk that is associated with additional benefits in terms of
      milk quality. Recent research on alternative markers for inflammatory reactions
      in the lactating cow, e.g. in mastitis, includes investigations of the acute
      phase protein, haptoglobin (Hp). So far, the content of Hp in milk has mainly
      been studied in relation to mastitis diagnostics, with little attention given to
      its importance for milk composition and technological properties. At present, Hp
      in milk is measured using ELISA, but this technique is not suitable for routine
      large-scale analysis. In recent years, optical biosensor technology has been used
      for automated and rapid quantitative analysis of different components in milk,
      but so far not for analysis of acute phase proteins. The aim of the present study
      was to develop a rapid and sensitive biosensor method to determine Hp in milk. An
      affinity sensor assay based on the interaction between Hp and haemoglobin was
      developed using surface plasmon resonance (SPR) biosensor technology. The assay
      was used to analyse Hp in composite milk samples from cows without any clinical
      signs of mastitis and quarter milk samples with a weak to strong reaction in the
      California Mastitis Test (CMT). A commercial ELISA for determination of Hp in
      milk was used for comparison. The limit of detection (LOD) of the biosensor assay
      was determined as 1.1 mg/l. Within-assay and between-day variations were
      determined both with bulk tank milk spiked with human Hp and with composite milk
      samples containing bovine Hp. Coefficients of variation varied between 3.6 and
      8.6% at concentrations between 4.0 and 12 mg/l, respectively. Agreement between
      the results obtained by the biosensor assay and the ELISA was satisfactory;
      however, the results obtained by the biosensor were generally lower than the
      results obtained by the ELISA. Possible explanations for this observation are
      discussed.

PMID- 16569278
TI  - Comparative sequence analysis of spa gene of Staphylococcus aureus isolated from
      bovine mastitis: characterization of an unusual spa gene variant.
AB  - The protein A encoding gene spa of four Staphylococcus aureus strains isolated
      from bovine clinical mastitis was amplified by PCR and sequenced. The four
      strains were selected after an initial screening of spa gene of 41 strains
      isolated from mastitic cows and were subjected to detailed investigations.
      According to the sequencing results the spa gene of three strains (M1, M2, M3)
      appeared with gene segments encoding five (E, D, A, B and C) and four (E, A, B
      and C) IgG binding domains for two (M1, M3) and one (M2) strain, respectively and
      with gene segments encoding four, two and two repeats of the octapeptide Xr
      repeats for the strains M1, M2 and M3, respectively. For the remaining Staph.
      aureus strain (M4) gene segments encoding IgG binding domains E, D and A and a
      new domain BC with a size of 219 bp could be observed. The BC domain appears,
      with a deletion of a 123 bp segment from the border region between both domains,
      as fused domain of both previously characterized domains. The Xr-region of this
      strain had 11 octapeptide repeats.

PMID- 16569279
TI  - Effects of graded levels of duodenal infusions of leucine on mammary uptake and
      output in lactating dairy cows.
AB  - Four multiparous Holstein cows, each equipped with a duodenal cannula and an
      ultrasonic mammary blood flow probe, were assigned to a 4x4 Latin square to
      measure the effects of duodenal infusions of Leu (0, 40, 80 and 120 g/d) on
      lactational responses and mammary metabolism of nutrients. Cows were fed a diet
      of 67.0% corn silage, 5.3% grass hay, 14.2% peas, 7.8% maize starch, 1.0% each of
      molasses, urea, and sodium bicarbonate and 2.4% minerals and vitamins.
      Requirements of the remaining 9 essential amino acids were met by infusing into
      the duodenum 323 g/d of a mixture of amino acids including, Ile, Val, Met, Lys,
      Trp, Phe, His, Thr, Arg, Tyr and Glu. Milk protein content and yield were highest
      with 40 g/d of Leu and then progressively declined. Milk fat content and yield
      were significantly decreased over the entire range of Leu infusions. Arterial
      concentrations of Leu increased linearly and corresponding mammary arterio-venous
      differences increased to a plateau with 80 g/d of Leu. As Leu infusions
      increased, extraction rates of Leu decreased linearly, whereas those of Ile, Val,
      Lys, Arg, Thr and Tyr were significantly increased. Leu was taken up by the
      mammary gland according to milk output with 0 and 40 g/d of Leu infused and then
      largely in excess. Based on responses of protein yield and mammary uptake to milk
      output ratio, Leu concentration in total amino acids absorbed in the small
      intestine needs to be close to 8.9% for optimal milk protein synthesis.

PMID- 16569280
TI  - Hypertonic NaCl infusions affect milk composition in goats.
AB  - The capability of goats to maintain milk production during water deprivation is
      remarkable and not yet fully understood. The aim of the present study was to
      investigate whether intravenous infusions of hypertonic NaCl cause release of
      both vasopressin and oxytocin and whether the peptides, in combination with the
      hyperosmolality, affect milk flow and milk composition. Six Swedish domestic
      landrace goats in their first to third lactation were milked every 30 min during
      experiments. Hypertonic NaCl (HNaCl) or isotonic NaCl (IsoNaCl) were infused for
      90 min. Goats were not allowed to drink during infusions. Plasma vasopressin
      concentration increased during HNaCl infusions, and did not change in response to
      IsoNaCl infusions. Plasma oxytocin concentration did not change during either
      infusion. Milk flow was maintained during the infusions. Milk fat concentration
      decreased in the three samples taken before onset of the infusions, but then
      increased gradually during HNaCl infusions, while it continued to fall during the
      IsoNaCl infusions. Milk osmolality followed the rise in plasma osmolality during
      the HNaCl infusions and did not change in IsoNaCl experiments. Milk lactose
      concentration increased throughout both series of experiments, the concentration
      being higher during HNaCl infusions. Milk protein concentration did not change
      during HNaCl infusions, but fell in the IsoNaCl experiments. It is concluded that
      the hyperosmolality in combination with elevated plasma vasopressin levels did
      not disturb the secretory activity of the mammary cells, but rather facilitated
      emptying of the alveolar milk. Such a mechanism may help to explain the sustained
      milk production in water deprived goats.

PMID- 16569281
TI  - Associations between somatic cell counts at calving or prior to drying-off and
      future somatic cell counts, in the remaining or subsequent lactation.
AB  - Composite milk somatic cell counts (CMSCC) from four separate datasets,
      containing 3338, 350, 1408 and 1404 herds, were used. All herds were enrolled in
      the Norwegian Dairy Herd Recording System (NDHRS). The aim was to investigate
      associations between CMSCC at calving or prior to drying-off and future CMSCC in
      the remaining or subsequent lactation. CMSCC was determined using Fossomatic 5000
      cell counters (Foss Electric, Hillerod, Denmark) according to IDF recommendations
      (International Dairy Federation, 1984) and a natural logarithmic transformation
      of the CMSCC data (lnCMSCC) was performed. Results obtained were arranged
      according to parity and lactation stage and regression models and general linear
      mixed models were applied, the latter model to account for clustering between
      herds. The best associations between CMSCC at calving or prior to drying-off and
      future CMSCC in the remaining or subsequent lactation were found by using at
      least two CMSCC test days after calving or prior to drying-off. The geometric
      mean of the second and third or the first three CMSCC test days explained 50% of
      the variation in future CMSCC in first parity cows. This information was
      accessible at 151 days in milk (DIM) in bimonthly tested herds, and at 87 DIM for
      monthly tested herds. There was not a large difference using two or three single
      consecutive weighted CMSCC test days compared with the geometric mean of two or
      three CMSCC test days. Our findings indicate the need of using at least two CMSCC
      test days and, if only one CMSCC test day is used, it should be obtained after 14
      d post-calving or preferably after 30 DIM.

PMID- 16569282
TI  - Dry matter intake precalving in cows offered fresh and conserved pasture.

PMID- 16569283
TI  - Bacteraemia due to ciprofloxacin-resistant Salmonella enterica serotype
      Choleraesuis in adult patients at a university hospital in Taiwan, 1996-2004.
AB  - Eighty-one adult patients with Salmonella enterica serotype Choleraesuis (S.
      Choleraesuis) bacteraemia treated at a university hospital from 1996 to 2004 were
      evaluated. Multivariate analysis with a logistic regression model was used to
      characterize risk factors for primary bacteraemia and mycotic aneurysm and to
      determine the association of clinical characteristics of patients based on
      ciprofloxacin susceptibility of the causative organism. The incidence per 100,000
      discharges was 0.76 in 1996 and 3.9 in 2004. The overall rate of ciprofloxacin
      resistance among these isolates was 59% (87 isolates) and the annual rate
      increased with time from 0% prior to 2000 to 80% in 2004. Among these patients,
      48 (59%) had primary bacteraemia and 13 (16%) had secondary bacteraemia with
      mycotic aneurysm. Seventy (86%) patients had fever at presentation, 22 (27%)
      developed shock during hospitalization, and eight (10%) died of S. Choleraesuis
      bacteraemia. Patients with immunocompromised conditions had a higher risk of
      developing primary bacteraemia (OR 18.442, P < 0.001). Hypertension (OR 15.434, P
      = 0.002) and male gender (OR 7.422, P = 0.039) were associated with mycotic
      aneurysm. Patients with mycotic aneurysm were more frequently infected with
      ciprofloxacin-susceptible isolates (P = 0.028) and ciprofloxacin-susceptible
      isolates were also more frequently associated with recurrent infection than
      ciprofloxacin-resistant isolates (P = 0.038). The incidence of S. Choleraesuis
      bacteraemia has increased in the past 8 years, and this increase is associated
      with the upsurge of ciprofloxacin-resistant isolates.

PMID- 16569285
TI  - The ever-expanding neuropeptide gene families in the nematode Caenorhabditis
      elegans.
AB  - Neuropeptides act as chemical signals in the nervous system to modulate
      behaviour. With the ongoing EST projects and DNA sequence determination of
      different genomes, the identification of neuropeptide genes has been made easier.
      Despite the relatively 'simple' repertoire of behaviours in the nematode
      Caenorhabditis elegans, this worm contains a surprisingly large and diverse set
      of neuropeptide genes. At least 109 genes encoding over 250 potential
      neuropeptides have been identified in C. elegans; all genes are likely to be
      expressed and many, if not all, of the predicted peptides are produced. The
      predicted peptides include: 38 insulin-like peptides, several of which are
      involved in development and reproductive growth, and over 70 FMRFamide-related
      peptides, some of which are involved in locomotion, reproduction, and social
      behaviour. Many of the C. elegans peptides are identical or highly similar to
      those isolated or predicted in parasitic nematodes, such as Ascaris suum,
      Haemonchus contortus, Ancylostoma caninum, Heterodera glycines and Meloidogyne
      arenaria, suggesting that the function of these peptides is similar across
      species. The challenge for the future is to determine the function of all the
      genes and individual peptides and to identify the receptors through which the
      peptides signal.

PMID- 16569286
TI  - Neuromuscular function in plant parasitic nematodes: a target for novel control
      strategies?
AB  - Over the last decade the need for new strategies and compounds to control
      parasitic helminths has become increasingly urgent. The neuromuscular systems of
      these worms have been espoused as potential sources of target molecules for new
      drugs which may address this need. One facet of helminth neuromuscular biology
      which has garnered considerable research interest is that of neuropeptidergic
      neurotransmission, particularly regarding parasites of humans and animals, as
      well as free-living nematode model species. This research interest has been
      piqued by the fact that neuropeptides have been demonstrated to be fundamentally
      important to nematode biology and thus may be of utility in this search for new
      drug targets. This review focuses on the neuropeptide biology of plant parasitic
      nematodes, a subject which has been comparatively neglected despite the fact that
      the search for alternative control measures also extends to these economically
      important parasites. We focus on the FMRFamide-like peptide (FLP) neuropeptides
      and the complexity and distribution of this peptide family in plant parasitic
      nematodes. Possible roles for FLPs in plant parasitic nematode behaviour, as
      elucidated by a combination of molecular imaging techniques and RNA interference
      (RNAi), are discussed. We propose that disruption of FLP neurosignalling in plant
      parasitic nematodes represents a novel form of pest control and speculate as to
      how this may be achieved.

PMID- 16569287
TI  - Inter-phyla studies on neuropeptides: the potential for broad-spectrum
      anthelmintic and/or endectocide discovery.
AB  - Flatworm, nematode and arthropod parasites have proven their ability to develop
      resistance to currently available chemotherapeutics. The heavy reliance on
      chemotherapy and the ability of target species to develop resistance has prompted
      the search for novel drug targets. In view of its importance to parasite/pest
      survival, the neuromusculature of parasitic helminths and pest arthropod species
      remains an attractive target for the discovery of novel endectocide targets.
      Exploitation of the neuropeptidergic system in helminths and arthropods has been
      hampered by a limited understanding of the functional roles of individual
      peptides and the structure of endogenous targets, such as receptors. Basic
      research into these systems has the potential to facilitate target
      characterization and its offshoots (screen development and drug identification).
      Of particular interest to parasitologists is the fact that selected neuropeptide
      families are common to metazoan pest species (nematodes, platyhelminths and
      arthropods) and fulfil specific roles in the modulation of muscle function in
      each of the three phyla. This article reviews the inter-phyla activity of two
      peptide families, the FMRFamide-like peptides and allatostatins, on motor
      function in helminths and arthropods and discusses the potential of neuropeptide
      signalling as a target system that could uncover novel endectocidal agents.

PMID- 16569288
TI  - Nematode neuropeptide receptors and their development as anthelmintic screens.
AB  - This review addresses the potential use of neuropeptide receptors for the
      discovery of anthelmintic agents, and particularly for the identification of non
      peptide ligands. It outlines which nematode neuropeptides are known and have been
      characterized, the published information on drug discovery around these targets,
      information about existing high- and low-throughput screening systems and finally
      the likely safety of neuropeptide mimetics.

PMID- 16569289
TI  - Resistance as a tool for discovering and understanding targets in parasite
      neuromusculature.
AB  - The problem of anthelmintic resistance prevents efficient control of parasites of
      livestock and may soon compromise human parasite control. Research into the
      mechanisms of resistance and the quest for diagnostic tools to aid control has
      required research that focuses on field resistance. On the other hand, resistant
      worms, including those kept in the laboratory, provide useful tools for studying
      drug action, especially at neuromuscular targets in worms. While the needs and
      directions of these research aims overlap, this review concentrates on research
      on drug targets. In this context, resistance is a useful tool for site of action
      confirmation. For example, correlations between molecular expression studies and
      resistance assays conducted on whole worms can strengthen claims for sites of
      anthelmintic action. Model systems such as Caenorhabditis elegans have been very
      useful in understanding targets but give a limited picture as it is now clear
      that resistance mechanisms in this worm are different from those in parasites.
      Accordingly, research on parasites themselves must also be performed. Resistant
      isolates of the sheep nematode parasite Haemonchus contortus are the most widely
      used for this purpose as in vivo, in vitro, physiological and molecular studies
      can be performed with this species. Neuromuscular target sites for the
      anthelmintics levamisole and ivermectin are the best studied and have benefited
      most from the use of resistant worm isolates. Resistance to praziquantel and the
      newer chemical groups should provide new tools to explore targets in the future.

PMID- 16569290
TI  - Classical transmitters and their receptors in flatworms.
AB  - The flatworm nervous system employs a wide repertoire of neuroactive substances,
      including small chemical messengers, the so called classical transmitters, and
      several types of neuropeptides. A large body of research accumulated over four
      decades has provided a wealth of information on the tissue localization and
      effects of these substances, their biochemistry and, recently, their molecular
      modes of action in all major classes of flatworms. This evidence will be
      reviewed, with particular emphasis on the small (classical) transmitters and the
      receptors that mediate their effects. One of the themes that will emerge from
      this discussion is that classical transmitters regulate core activities such as
      movement, metabolism and transport, and thus are essential for survival of the
      organism. In addition, the evidence shows that flatworms have multiple
      neurotransmitter receptors, many with unusual pharmacological features, which
      make them particularly attractive as drug targets. Understanding the molecular
      basis of these distinctive properties, and developing new, more specific receptor
      agonists and antagonists will undoubtedly become a major challenge in future
      research.

PMID- 16569292
TI  - Neuropeptide signalling systems in flatworms.
AB  - Two distinct families of neuropeptides are known to endow platyhelminth nervous
      systems - the FMRFamide-like peptides (FLPs) and the neuropeptide Fs (NPFs).
      Flatworm FLPs are structurally simple, each 4-6 amino acids in length with a
      carboxy terminal aromatic-hydrophobic-Arg-Phe-amide motif. Thus far, four
      distinct flatworm FLPs have been characterized, with only one of these from a
      parasite. They have a widespread distribution within the central and peripheral
      nervous system of every flatworm examined, including neurones serving the
      attachment organs, the somatic musculature and the reproductive system. The only
      physiological role that has been identified for flatworm FLPs is myoexcitation.
      Flatworm NPFs are believed to be invertebrate homologues of the vertebrate
      neuropeptide Y (NPY) family of peptides. Flatworm NPFs are 36-39 amino acids in
      length and are characterized by a caboxy terminal GRPRFamide signature and
      conserved tyrosine residues at positions 10 and 17 from the carboxy terminal.
      Like FLPs, NPF occurs throughout flatworm nervous systems, although less is known
      about its biological role. While there is some evidence for a myoexcitatory
      action in cestodes and flukes, more compelling physiological data indicate that
      flatworm NPF inhibits cAMP levels in a manner that is characteristic of NPY
      action in vertebrates. The widespread expression of these neuropeptides in
      flatworm parasites highlights the potential of these signalling systems to yield
      new targets for novel anthelmintics. Although platyhelminth FLP and NPF receptors
      await identification, other molecules that play pivotal roles in neuropeptide
      signalling have been uncovered. These enzymes, involved in the biosynthesis and
      processing of flatworm neuropeptides, have recently been described and offer
      other distinct and attractive targets for therapeutic interference.

PMID- 16569291
TI  - Functional genomics of nematode acetylcholinesterases.
AB  - Acetylcholine is the major excitatory neurotransmitter controlling motor
      activities in nematodes, and the enzyme which hydrolyses and inactivates
      acetylcholine, acetylcholinesterase, is thus essential for regulation of
      cholinergic transmission. Different forms of acetylcholinesterase are encoded by
      multiple genes in nematodes, and analysis of the pattern of expression of these
      genes in Caenorhabditis elegans suggests that they perform non-redundant
      functions. In addition, many parasitic species which colonise host mucosal
      surfaces secrete hydrophilic variants of acetylcholinesterase, although the
      function of these enzymes is still unclear. Acetylcholinesterases have a history
      as targets for therapeutic agents against helminth parasites, but anti
      cholinesterases have been used much more extensively as pesticides, for example
      to control crop damage and ectoparasitic infestation of livestock. The toxicity
      associated with these compounds (generally organophosphates and carbamates) has
      led to legislation to withdraw them from the market or restrict their use in many
      countries. Nevertheless, acetylcholinesterases provide a good example of a
      neuromuscular target enzyme in helminth parasites, and it may yet be possible to
      develop more selective inhibitors. In this article, we describe what is known
      about the structure and function of vertebrate cholinesterases, illustrate the
      molecular diversity and tissue distribution of these enzymes in C. elegans, and
      discuss to what extent this may represent a paradigm for nematodes in general.

PMID- 16569293
TI  - Signal transduction in larval trematodes: putative systems associated with
      regulating larval motility and behaviour.
AB  - The multi-host lifestyle of parasitic trematodes necessitates their ability to
      communicate with their external environment in order to invade and navigate
      within their hosts' internal environment. Through recent EST and genome
      sequencing efforts, it has become clear that members of the Trematoda possess
      many of the elaborate signal transduction systems that have been delineated in
      other invertebrate model systems like Drosophila melanogaster and Caenorhabditis
      elegans. Gene homologues representing several well-described signal receptor
      families including receptor tyrosine kinases, receptor serine tyrosine kinases, G
      protein-coupled receptors and elements of their downstream signalling systems
      have been identified in larval trematodes. A majority of this work has focused on
      the blood flukes, Schistosoma spp. and therefore represents a narrow sampling of
      the diverse digenean helminth taxon. Despite this fact and given the substantial
      evidence supporting the existence of such signalling systems, the question then
      becomes, how are these systems employed by larval trematodes to aid them in
      interpreting signals received from their immediate environment to initiate
      appropriate responses in cells and tissues comprising the developing parasite
      stages? High-throughput, genome-wide analysis tools now allow us to begin to
      functionally characterize genes differentially expressed throughout the
      development of trematode larvae. Investigation of the systems used by these
      parasites to receive and transduce external signals may facilitate the creation
      of technologies for achieving control of intramolluscan schistosome infections
      and also continue to yield valuable insights into the basic mechanisms regulating
      motility and behaviour in this important group of helminths.

PMID- 16569294
TI  - Drug resistance and neurotransmitter receptors of nematodes: recent studies on
      the mode of action of levamisole.
AB  - Here we review recent studies on the mode of action of the cholinergic
      anthelmintics (levamisole, pyrantel etc.). We also include material from studies
      on the free living nematode Caenorhabditis elegans. The initial notion that these
      drugs act on a single receptor population, while attractive, has proven to be an
      oversimplification. In both free living and parasitic nematodes there are
      multiple types of nicotinic acetylcholine receptor (nAChR) on the somatic
      musculature. Each type has different (sometimes subtly so) pharmacological
      properties. The implications of these findings are: (1) combinations of
      anthelmintic that preferentially activate a broad range of nAChR types would be
      predicted to be more effective; (2) in resistant isolates of parasite where a
      subtype has been lost, other cholinergic anthelmintics may remain effective. Not
      only are there multiple types of nAChR, but relatively recent research has shown
      these receptors can be modulated; it is possible to increase the response of a
      parasite to a fixed concentration of drug by altering the receptor properties
      (e.g. phosphorylation state). These findings offer a potential means of
      increasing efficacy of existing compounds as an alternative to the costly and
      time consuming development of new anthelmintic agents.

PMID- 16569295
TI  - Glutamate-gated chloride channels and the mode of action of the
      avermectin/milbemycin anthelmintics.
AB  - The macrocyclic lactones are the biggest selling and arguably most effective
      anthelmintics currently available. They are good substrates for the P
      glycoproteins, which might explain their selective toxicity for parasites over
      their vertebrate hosts. Changes in the expression of these pumps have been
      implicated in resistance to the macrocyclic lactones, but it is clear that they
      exert their anthelmintic effects by binding to glutamate-gated chloride channels
      expressed on nematode neurones and pharyngeal muscle cells. This effect is quite
      distinct from the channel opening induced by glutamate, the endogenous
      transmitter acting at these receptors, which produces rapidly opening and
      desensitising channels. Ivermectin-activated channels open very slowly but
      essentially irreversibly, leading to a very long-lasting hyperpolarisation or
      depolarisation of the neurone or muscle cell and therefore blocking further
      function. Molecular and genetic studies have shown that there are multiple GluCl
      isoforms in both free-living and parasitic nematodes: the exact genetic make-up
      and functions of the GluCl may vary between species. The known expression
      patterns of the GluCl explain most of the observed biological effects of
      treatment with the macrocyclic lactones, though the reason for the long-lasting
      inhibition of larval production in filarial species is still poorly understood.

PMID- 16569296
TI  - Ca2+ signalling, voltage-gated Ca2+ channels and praziquantel in flatworm
      neuromusculature.
AB  - Transient changes in calcium (Ca2+) levels regulate a wide variety of cellular
      processes, and cells employ both intracellular and extracellular sources of Ca2+
      for signalling. Praziquantel, the drug of choice against schistosomiasis,
      disrupts Ca2+ homeostasis in adult worms. This review will focus on voltage-gated
      Ca2+ channels, which regulate levels of intracellular Ca2+ by coupling membrane
      depolarization to entry of extracellular Ca2+. Ca2+ channels are members of the
      ion channel superfamily and represent essential components of neurons, muscles
      and other excitable cells. Ca2+ channels are membrane protein complexes in which
      the pore-forming alpha1 subunit is modulated by auxiliary subunits such as beta
      and alpha2delta. Schistosomes express two Ca2+ channel beta subunit subtypes: a
      conventional subtype similar to beta subunits found in other vertebrates and
      invertebrates and a novel variant subtype with unusual structural and functional
      properties. The variant schistosome beta subunit confers praziquantel sensitivity
      to an otherwise praziquantel-insensitive mammalian Ca2+ channel, implicating it
      as a mediator of praziquantel action.

PMID- 16569297
TI  - Screening for chronic glaucoma.

PMID- 16569298
TI  - Nuchal translucency thickness measurements for fetal aneuploidy screening: Log NT
      MoM or Delta-NT, performer-specific medians and ultrasound training.
AB  - OBJECTIVES: To evaluate in fetal aneuploidy screening the desirability of using
      Fetal Medicine Foundation (FMF) normal medians of nuchal translucency thickness
      (NT) measurements or performer-specific medians, and whether the NT measurements
      should be expressed as Delta-NT or Log NT-MoM values. SETTINGS: First trimester
      combined screening programme in a low risk population in Flanders, Belgium
      (Algemeen Medisch Laboratorium, Antwerp). METHODS: Pregnancies unaffected by
      trisomy 21 (T21) were screened by FMF-trained or other ultrasonographers.
      Performer-specific NT medians were established for FMF-trained and other
      ultrasonographers. NCSS Statistical Software was used to establish probability
      plots for Log NT-MoM and Delta-NT values, relative to performer-specific
      references or to the FMF-reference. RESULTS: A total of 16,096 pregnancies were
      evaluated. Six FMF-trainees and five other ultrasonographers each performed
      between 83 and 658 NT measurements. For the FMF-trainees, FMF-specific NT-MoM
      medians were close to one at a crown-rump length (CRL) between 50 and 80 mm,
      whereas the population-specific NT-MoM medians of the other ultrasonographers
      were close to one at a CRL between 40 and 80 mm. Performer-specific Delta-NT
      values fitted a Gaussian distribution between the 5th and 90th percentiles, while
      for the Log NT-MoM values this was between the 10th and 95th percentiles.
      CONCLUSION: We conclude that (i) the use of screening would benefit from
      performer-specific NT-medians based on Log NT-MoM values; (ii) the use of Log NT
      MoM values is marginally better than the use of delta-NT MoMs; and (iii) NT
      measurements are valid at about 10 weeks (crown-rump length 40-45 mm) as well as
      at 11-13 weeks.

PMID- 16569299
TI  - Using record linkage and manual follow-up to evaluate the Victorian maternal
      serum screening quadruple test for Down's syndrome, trisomy 18 and neural tube
      defects.
AB  - OBJECTIVES: The Genetic Health Services Victoria maternal serum screening (MSS)
      quadruple test has been available to pregnant women in Victoria since 1996. The
      objectives of this study were to follow up the pregnancies screened by MSS
      between July 1998 and June 2000 and to determine the performance characteristics
      of the test for Down's syndrome, trisomy 18 and neural tube defects (NTDs).
      METHODS: MSS results were matched to pregnancy outcome information from the
      Perinatal Data Collection Unit and Birth Defects Register, using automated
      probabilistic record linkage. For unmatched pregnancies, manual follow-up was
      carried out by contacting referring doctors and hospitals, resulting in a very
      high follow-up rate of 99.2% (18,989/19,143). RESULTS: The sensitivity of MSS for
      Down's syndrome was 85% (23/27-95%CI 72-99%) with a falsepositive rate (FPR) of
      6.8% (risk threshold >or= 1 in 250). While using a fixed 5% FPR, the sensitivity
      for Down's syndrome was slightly lower (78%). The sensitivity for trisomy 18 was
      44% (4/9 - 95% CI 12-77%) with a FPR of 0.5% (risk threshold of >or= 1 in 200).
      11 of the 15 (73 - 95%CI 51-97%) cases of open NTDs were detected from screening,
      with a 1% FPR (risk threshold alpha-fetoprotein [AFP] >or=2.5 MoM). All cases of
      anencephaly had increased AFP levels. CONCLUSION: Probabilistic record linkage
      and manual follow-up is an efficient method for ascertainment of pregnancy
      outcomes, with a higher follow-up rate than that reported in similar studies. MSS
      should remain an available option for all pregnant women in Victoria, with test
      characteristics comparable with other recent reports of the quadruple test.

PMID- 16569300
TI  - An analysis of the costs of implementing the National Newborn Hearing Screening
      Programme in England.
AB  - OBJECTIVE: The primary aim of this analysis was to prospectively assess the full
      economic costs associated with implementing Newborn Hearing Screening Programme
      (NHSP) based on a two-stage screen, transient evoked otoacoustic emissions
      followed, if there is no clear response, by automated auditory brainstem
      response. Economic data were also collected from the Infant Distraction Test
      Screening (IDTS) service performed by health visitors at around eight months of
      age, which was being phased out. A comparison of costs and outcomes associated
      with NHSP and IDTS was conducted. DESIGN: 20 NHSP sites were invited to provide
      detailed cost data on NHSP implementation and 14 of these sites were selected to
      provide costs on the IDTS service that was being supplanted. RESULTS: There was
      marked variability in the costs. Given the higher yield of NHSP sites, the
      average cost per case detected across NHSP sites (31,410 pounds/case) was
      approximately half that of IDTS sites (69,919 pounds/case). Including family
      costs, the average total cost per case of NHSP (34,826 pounds/case) was almost a
      quarter of IDTS (117,942 pounds/case). CONCLUSIONS: Family costs and cost per
      case associated with NHSP are considerably less than that with IDTS. These
      findings support the policy of implementation of NHSP and the phasing out of the
      IDTS.

PMID- 16569301
TI  - Maternal anxiety following newborn hearing screening: the moderating role of
      knowledge.
AB  - OBJECTIVES: To describe the impact upon maternal anxiety of newborn hearing
      screening and examine the Possible moderating role of knowledge. METHODS:
      Questionnaires assessing maternal state anxiety, worry and certainty about the
      baby's hearing, and knowledge about screening, were sent to four groups of
      mothers three weeks after screening: Group 1 consisted of mothers whose babies
      had clear responses on a first or second screening test (n=103); Group 2
      consisted of mothers whose babies had clear responses on the third screening test
      (n=81); Group 3 consisted of mothers whose babies did not have clear responses in
      one ear at the third screening test and were referred for audiological assessment
      (n=105); and Group 4 consisted of mothers whose babies did not have clear
      responses in either ear at the third hearing test and were referred for
      audiological assessment (n=55). RESULTS: Although mean anxiety levels were in the
      normal range, there was a significant trend for anxiety to rise as testing
      increased (F(1,327)=4.280, P<0.05). Worry increased significantly
      (F(1,337)=70.432, P<0.001) and certainty decreased significantly
      (F(1,339)=27.474, P=0.001) as the number of tests increased. Although total
      knowledge did not significantly moderate anxiety (R(2)=0.016, P=0.096), there was
      a significant interaction between mothers' group and one knowledge item,
      understanding that receipt of no clear responses was unlikely to mean that the
      baby had a hearing loss: mothers in Group 4 who understood this had lower anxiety
      (F(3,323)=4.791, P<0.01) and lower worry (F(3,332)=3.565, P<0.01) compared with
      mothers who did not. CONCLUSIONS: Understanding the meaning of being recalled
      following screening may avoid some of the anxiety associated with this.

PMID- 16569302
TI  - Prevalence of G6PD deficiency and knowledge of diagnosis in a sample of
      previously unscreened Lebanese males: clinical implications.
AB  - The incidence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Lebanon
      is estimated at 10 per 1,000 in men and 0.4 per 1,000 in women. A community-based
      cluster sampling survey was conducted in 15 villages in all areas in Lebanon. The
      survey found 36 cases of G6PD deficiency among 3,000 men aged 14 years and above,
      yielding a cumulative incidence rate of 12 per 1,000. Of those 36 cases, 28
      (77.8%) knew of their problem since they had already suffered at least one severe
      anaemia crisis in their childhood following the ingestion of raw green fava
      beans. The remaining 22.2% were not aware at all of their defect. These findings
      confirm that G6PD is a common genetic problem in Lebanon. The efficiency of early
      screening programmes in terms of preventing severe, at times potentially lethal,
      haemolytic crises is currently being investigated.

PMID- 16569303
TI  - Screening for scoliosis: do we have indications for effectiveness?
AB  - OBJECTIVE: The effectiveness of screening for scoliosis has not been established.
      This study investigated whether patients with adolescent idiopathic scoliosis
      detected by screening are detected in an earlier stage of the clinical course,
      and whether these patients have better outcome than otherwise detected patients.
      SETTING: The study is a retrospective follow-up study of patients with adolescent
      idiopathic scoliosis who had completed treatment with a brace, by surgery, or
      with a brace followed by surgery. Of the 143 patients (born on or after 1 January
      1984) consecutively recruited from 12 hospitals in the Netherlands, 125 (87%)
      agreed to participate. Of these, 51 patients were treated with a brace only and
      74 patients were operated on. Screening for scoliosis is carried out in 80% of
      Dutch children. METHODS: Data on being screen detected or otherwise detected and
      Cobb angle at diagnosis were collected using youth health-care files, medical
      files and interviews by telephone with the patients. RESULTS: About 55% of the
      patients were detected by screening (programme sensitivity). Screen-detected
      patients had a significantly smaller Cobb angle at diagnosis (28 degrees versus
      40 degrees ; P<0.01) and had a 73% lower chance of having had surgery (45% versus
      75%; P<0.01) than otherwise-detected patients. CONCLUSION: In the present study,
      two essential prerequisites necessary for a screening programme for scoliosis to
      be effective have been met. However, definite proof of the effectiveness of
      screening still needs to be established because length bias and over-treatment
      bias cannot be ruled out using this design.

PMID- 16569304
TI  - Service screening mammography reduces breast cancer mortality among elderly women
      in Turku.
AB  - OBJECTIVES: The aim of this study was to assess the effects of service screening
      mammography on breast carcinoma incidence and refined mortality among women aged
      55-69 at entry in three cities employing different screening policies. METHODS:
      Since 1987, the city of Turku, Finland, has provided service screening
      mammography for women aged 55-69 at entry (in 1987), and Tampere provided
      screening for women aged 55-59 at entry, whereas Helsinki did not screen any of
      these age groups. The incidence of breast carcinoma during the screening period
      1987-97 in women born in 1918-32 (1918-22, 1923-27, 1928-32) was compared with
      incidence during the pre-screening period 1976-86 in women born in 1907-21 (1907
      11, 1912-16, 1917-21) in each city. The follow-up for mortality was four years
      longer. RESULTS: Breast carcinoma incidence was 31-38% higher in the screening
      period in all three cities irrespective of screening. In breast carcinoma
      mortality, no significant changes were seen in Helsinki or Tampere. In Turku, a
      36% mortality reduction (relative risk [RR] 0.64; 95% confidence interval [CI]
      0.47-0.88; P=0.007) in the whole study population and a 47% reduction in women
      aged 65-69 at entry (RR 0.53; 95% CI 0.28-0.99; P=0.047) were seen. CONCLUSIONS:
      The incidence of breast carcinoma increased in all study cities irrespective of
      screening. The comprehensive screening programme in Turku including women aged 55
      69 at entry was associated with a significant reduction in breast carcinoma
      mortality. The pronounced decrease in mortality in the oldest age group (65-69
      years at entry) also indicated that women of this age group greatly benefit from
      mammography screening.

PMID- 16569305
TI  - What happens when organization of cervical cancer screening is delayed or
      stopped?
AB  - OBJECTIVES: Many countries rely on opportunistic screening, and data on its
      effectiveness are asked for. We assessed the impact on cervical cancer incidence
      and mortality of opportunistic screening compared with organized screening.
      SETTING: Women aged 30-64 in Denmark, 1973-2002; 16 counties with different
      screening strategies. METHODS: Cumulative incidence and mortality rates for women
      aged 30-64 by county. Poisson regression of incidence and mortality rates by age,
      calendar period and county. Interaction between type of county and calendar
      period measured the difference between counties with screening organized early
      versus late in time. RESULTS: A statistically significant interaction was found
      between type of county and calendar period (P=0.0151) for cervical cancer
      incidence, but not for cervical cancer mortality (P=0.9593). The interaction
      terms were not statistically significant when a comparison was made between a
      single county in which an organized programme was interrupted for an 11-year
      period and other counties. There was, however, a statistically significant
      increased incidence and mortality rates at the restart of the organized
      programme. CONCLUSION: Organization of cervical cancer screening accelerated the
      decline in cervical cancer incidence, compared with the trend in areas relying on
      opportunistic screening. No impact could be measured of the screening
      organization on cervical cancer mortality. A decade long stop of an organized
      screening programme was associated with a temporary increase in cervical cancer
      incidence and mortality. Coverage remains a key quality indicator in the ongoing
      modernization of screening technology.

PMID- 16569306
TI  - Does the 'inverse screening law' apply to oral cancer screening and regular
      dental check-ups?
AB  - OBJECTIVE: Early detection through regular screening is a measure used in certain
      cancer prevention strategies. This approach has been advocated for the prevention
      of oral cancers in the UK. The objective of this study was to assess whether
      people at higher risk of oral cancer in the UK visit dentists on a regular basis,
      and thereby afford opportunities for oral cancer screening. METHODS: Data from
      two large national surveys were used. Firstly, data from the Health Survey for
      England, 2001, were used to assess the relationship between dental attendance
      (the outcome measure) and recognized oral cancer risk factors; there were 13,784
      participants with complete data. We used known risk factors for oral cancer (age
      >40 years, male sex, alcohol intake >28 units per week, cigarettes >20 per day,
      and fruit and vegetables <5 times a day) to generate a risk score for oral
      cancer. Logistic regression was used to compute the odds ratios for regular
      dental attendance according to risk score. All analyses used education and social
      class as covariates. We also used data from the British Household Panel Survey to
      assess whether dental attendance behaviour is sustained over a set period of time
      (5,547 participants with complete data). RESULTS: In persons in the higher risk
      category (as defined above) of the five risk factors, age, sex, alcohol, smoking,
      and fruit/vegetables, 68%, 56%, 52%, 43% and 60%, respectively reported regular
      dental check-ups. In persons with 0, 1, 2, 3, 4 and 5 of these risk factors, the
      odds ratio for regular dental check-ups was 1.00, 0.93, 0.81, 0.64, 0.50 and
      0.28, respectively. The probability of regular dental attendance was low in all
      groups with a higher risk of oral cancer. In the longitudinal sample, the low
      probability of visiting a dentist regularly was stable over time. CONCLUSION:
      Opportunistic screening for oral cancer in general dental practice in the UK is
      unlikely to be an effective preventive strategy.

PMID- 16569307
TI  - Guidance on terminology.

PMID- 16569309
TI  - Advances in oocyte cryopreservation technology will eventually blur the ethical
      and moral boundaries between compensated egg sharing and commercialized oocyte
      donation.
AB  - Compensated egg sharing was originally conceived as a patient self-help co
      operative scheme to avoid overt 'commodification' of donor oocytes and prevent
      doctors and medical institutions from acting as 'brokers' of donated human
      material. As such, egg sharing is an ethically justifiable and much-preferred
      alternative to commercialized oocyte donation. However, recent advances in oocyte
      cryopreservation technology are likely to blur the ethical and moral boundaries
      between compensated egg sharing and commercialized oocyte donation. The banking
      of cryopreserved oocytes would negate the requirement for donors and recipients
      in egg sharing to have co-ordinated and synchronized treatment cycles. Instead,
      fertility doctors and medical institutions can now offer subsidized fertility
      treatment upfront to any patient willing to donate a portion of her retrieved
      cohort of oocytes for banking and subsequent donation. Thus, more opportunity is
      now open for them to act as 'middle-man' to broker the transaction of oocytes
      between donor and recipient, which would inevitably result in overt
      'commodification' of donated human material. Administrative and processing fees
      will de finitely be billed to prospective recipients, for banking and storage of
      the cryopreserved oocytes, which would mean that a direct profit can now be made
      from the transaction of oocytes between donor and recipient.

PMID- 16569310
TI  - Advanced oocyte cryopreservation will not undermine the practice of ethical egg
      sharing.
AB  - The fear that the ethics and practice of egg sharing will be undermined by the
      growing success of oocyte cryopreservation is not based on published evidence.
      Separate contracts and directed counselling of donors and recipients as required
      by law in the UK provide protection against potential pitfalls with egg sharing.
      The cost and waiting time for egg donation might even fall should oocyte
      cryopreservation become a practicable procedure.

PMID- 16569311
TI  - To add or not to add LH: comments on a recent commentary.
AB  - From a period of time when LH activity supplementation in stimulation protocols
      for assisted reproductive technology was questioned, recent scientific evidence
      seems to prove a role of LH activity in optimizing the clinical results of
      certain subgroups. Until now, apart from the hypogonadotrophic hypogonadal
      patient, two subgroups of patients have attracted attention: patients over 35
      years of age, and normogonadotrophic patients with an initial low response to
      recombinant FSH (rFSH). However, in a recent paper, another subgroup of patients
      has been identified: normogonadotrophic patients with high endogenous LH levels
      (>1.99 IU/l) on day 8 of stimulation after a long GnRH agonist down-regulation.
      By adding recombinant LH (rLH) from day 8 to the stimulation protocol, this
      subgroup of patients achieved good implantation rates, similar to those of
      patients with lower LH levels. Interestingly, the dynamics of the endogenous LH
      levels during down-regulation in this group of patients differed from those of
      patients with lower LH levels. The immunoreactivity of the LH molecule does not
      necessarily reflect the bioactivity, which might explain the beneficial effect of
      LH activity supplementation in patients with high endogenous LH levels after down
      regulation. Future studies should be focused on subgroups to further explore the
      effect of LH activity supplementation in assisted reproduction techniques.

PMID- 16569312
TI  - Alternative solutions to the current situation of oocyte donation in Singapore.
AB  - The rising incidence of age-related female infertility in Singapore, coupled with
      the prohibition on commercialized oocyte donation and egg sharing, has resulted
      in a severe shortage of donor oocytes. Infertile women are routinely encouraged
      by fertility doctors here to seek their close relatives and friends as
      prospective oocyte donors, which does not alleviate the shortage. A number of
      alternative solutions are discussed. The use of substantial financial
      remuneration to encourage oocyte donation is rejected as being legally, ethically
      and morally incompatible with present day Singaporean society. Egg sharing in
      return for subsidized fertility may have a strong case for ethical justification,
      but implementation would need amendment of the current legislation in Singapore.
      Cross- and mirror-exchange oocyte donations face less of a legal challenge in
      Singapore and also have a strong case for ethical justification. However, special
      consideration must be given to the unique socio-cultural values of Singaporean
      society, i.e. traditional Chinese culture. Finally, if no changes are made to
      restrictive regulations governing oocyte donation in Singapore, and shortage of
      donor oocytes still persists, then reproductive tourism abroad may be the
      solution for some patients; referrals by local fertility doctors are unlikely to
      be allowed in Singapore.

PMID- 16569313
TI  - New concepts on the causes of recurrent miscarriage.

PMID- 16569314
TI  - A positive-selection function for microRNA: an adaptor hypothesis revisited.
AB  - A hypothesis for coding different combinations of mRNA segments by a novel
      postulated function of microRNAs (miRNA) is presented. In this hypothesis, miRNA
      act as both coding adaptors and ligating enzymes. This hypothesis postulates an
      enzyme-substrate intermediate comprising a RNA triplex structure consisting of a
      miRNA adaptor and two mRNA configured as two turns of an A-form RNA helix.
      Postulating the existence of differentially expressed sets of adaptors (codes)
      may explain biological functions such as imprinting, differentiation,
      immunological escape and immunological tolerance, inter alia.

PMID- 16569316
TI  - Quality of life of patients undergoing ovarian stimulation with injectable drugs
      in relation to medical practice in France.
AB  - The French study VISION is a multicentric, prospective and retrospective study,
      designed first to evaluate patients' quality of life during ovarian stimulation
      for ovulation induction, intrauterine insemination (IUI) or IVF, and secondly to
      analyse current medical practice in France. Answers were directly entered on a
      pocket PC. The study was conducted from January to August 2004 and 186
      practitioners filled in a total of 1476 questionnaires. The percentages for the
      different treatments used were analysed according to type of technique [ovulation
      induction, IUI, IVF/intracytoplasmic sperm injection (ICSI)], type of product
      used [urinary gonadotrophins, recombinant FSH (rFSH), gonadotrophin-releasing
      hormone (GnRH) agonists and antagonists] and methods of administration
      (intramuscularly, subcutaneously, use of Pen-injector, nurses or self
      injections). Initial and total amounts of urinary gonadotrophins per cycle were
      approximately 30% higher compared with rFSH for IUI and IVF. Generally, the
      impact of these treatments on professional or social life was less than expected.
      Patients saw self-injection as a significant improvement in their life,
      especially when using an injection pen, and when other drugs were also self
      injected during treatment (human chorionic gonadotrophin, GnRH agonists or
      antagonists). Clear information is necessary to increase patient's compliance to
      the treatment. Simplification will make these procedures more patient-friendly
      and less of a struggle.

PMID- 16569317
TI  - Effect of gonadotrophin stimulation on mouse oocyte quality and subsequent
      embryonic development in vitro.
AB  - In-vivo-matured oocytes were collected from naturally ovulated and superovulated
      [pregnant mare's serum gonadotrophin (PMSG) + human chorionic gonadotrophin
      (HCG)] mice. Immature oocytes were retrieved from naturally cycling mice and from
      mice primed with PMSG. The percentages of cleavage and blastocyst formation were
      significantly different (P < 0.05) between in-vivo- and in-vitro-matured oocytes.
      Blastocyst formation rate was significantly higher (P < 0.05) in immature oocytes
      derived from PMSG-primed mice, and the percentages of oocytes with comet tails,
      and their length, were significantly higher and longer respectively in in-vitro
      matured oocytes. Total cell numbers of blastocysts were also significantly
      different (P < 0.05) between in-vivo- and in-vitro-matured oocytes, but there
      were also no differences in ratio of trophectoderm (TE)/inner cell mass (ICM). In
      conclusion, in-vivo-matured mouse oocytes were more competent than those matured
      in-vitro, perhaps due to a lesser degree of DNA damage. Embryonic development
      capacity of in-vivo-matured oocytes is not promoted by ovarian stimulation.
      Gonadotrophin priming prior to immature mouse oocyte retrieval is beneficial to
      subsequent embryonic development.

PMID- 16569319
TI  - Rate of cell division and weight of neonates following IVF.
AB  - The present study tested the hypothesis that embryos with a lower number of cells
      on day 3 would be associated with infants born of lower weight. Singleton births
      (n = 447) were analysed to assess mean birth weight according to mean cell number
      in the transferred cohort. Mean birth weight increased with increasing average
      cell number. Each increase of one in average cell number was associated with a
      predicted increase in birth weight of 42.7 g (P = 0.01). This association was
      present only without assisted hatching, where an increase of one in average cell
      number was associated with a predicted increase of 79.1 g (P = 0.0005).
      Intracytoplasmic sperm injection was not associated with any change in birth
      weight. Demonstration of causality is limited because it is impossible to know
      which embryo in the transferred group implanted and grew into a fetus. Complete
      data were also lacking on some factors that influence birth weight. However, our
      data indicate that mean cell number on day 3 is positively associated with birth
      weight, but only without assisted hatching. Assisted hatching of slower-cleaving
      embryos may normalize birth weight distribution to that of faster-cleaving
      embryos.

PMID- 16569320
TI  - Multiple thrombophilic gene mutations are risk factors for implantation failure.
AB  - While the role of inherited thrombophilia has been accepted as a cause of
      recurrent late pregnancy complications, the contribution of mutated thrombophilic
      genes to implantation failure has not been studied. Proteins involved in
      fibrinolysis are necessary for trophoblast invasion into the endometrium. This
      study compared the prevalence of 10 thrombophilic gene mutations among 42 women
      with a history of recurrent implantation failure after IVF-embryo transfer with
      20 fertile control women. Buccal swabs were taken from all of the women for DNA
      analyses. Women with a history of implantation failure after IVF-embryo transfer
      displayed a higher prevalence of PAI-1 4G/5G mutations than controls (P = 0.007).
      No differences in the frequency of the other specific gene mutations were
      detected. However, the prevalence of total gene mutations among patients with
      implantation failure was significantly higher than among controls. More than
      three gene mutations among the 10 genes studied were observed in 74% of women
      with implantation failure and 20% of controls (P = 0.0004). It is concluded that
      inherited thrombophilias are associated with implantation failure. This
      association is manifest by total number of mutations as well as with PAI-1
      mutations.

PMID- 16569321
TI  - Pre-embryonic diagnosis for Sandhoff disease.
AB  - Embryos found to be abnormal during preimplantation genetic diagnosis (PGD) are
      discarded or analysed to confirm the diagnosis. To overcome this limitation,
      which is unacceptable in some communities and ethnic groups, pre-embryonic
      genetic diagnosis has been introduced, involving sequential first and second
      polar body analysis followed by transfer of embryos deriving from the mutation
      free oocytes, while removing from culture and freezing the mutant oocytes at the
      pronuclear stage. The technique is applied here to PGD of Sandhoff disease caused
      by 16-kb deletion of the hexosaminidase B gene for a couple with a religious
      objection to discarding embryos irrespective of embryo genotype. Of 16 oocytes
      tested in a standard IVF protocol for 16-kb deletion, simultaneously with five
      linked polymorphic markers, eight were predicted mutant and frozen prior to
      syngamy, with the remaining eight, found to be free of mutation, further cultured
      and confirmed unaffected using blastomere biopsy. The transfer of two of these
      embryos resulted in birth of an unaffected child, demonstrating feasibility of
      pre-embryonic diagnosis to avoid embryo discard.

PMID- 16569324
TI  - Wide range of chromosome abnormalities in the embryos of young egg donors.
AB  - Embryo chromosome studies show high rates of abnormalities, above 50%, but most
      embryos studied were from patients aged 35 and older. The objectives of this
      study were firstly, to evaluate the rate of chromosome abnormalities in embryos
      from young egg donors, and secondly, to compare the range of chromosome
      abnormality rates between donors and non-egg donor cycles, both undergoing
      preimplantation genetic diagnosis (PGD) for infertility using fluorescence in
      situ hybridization analysis with probes for chromosomes X, Y, 13, 15, 16, 18, 21,
      and 22. On average, only 43% of the embryos were chromosomally normal, while the
      comparison group had euploidy rates between 34 (age group 18-34) (P < 0.001) and
      21% (age group 40-45) (P < 0.001). There was considerable variation between donor
      cycles, with almost one-third having less than 30% normal embryos. Also, within
      donors and recipients repeating several IVF cycles with PGD, only 29-56% of the
      second PGD cycles had similar rates of normal embryos to the first cycle, while
      in the comparison group it was 64%. The results can explain why some egg donors
      are successful whereas others are not, and may also show that a policy of PGD for
      first time egg donors is appropriate and indicated.

PMID- 16569323
TI  - Which patients with recurrent implantation failure after IVF benefit from PGD for
      aneuploidy screening?
AB  - Patients with recurrent IVF failure are defined as patients who are younger than
      37 years and who had at least three consecutive unsuccessful IVF/intracytoplasmic
      sperm injection (ICSI) cycles with good quality embryos. These patients might be
      predisposed to chromosome errors in their embryos and therefore might benefit
      from preimplantation genetic diagnosis for aneuploidy screening (PGD-AS). This
      technique is, however, expensive and some normal embryos might be lost due to the
      error rate. The aim of this retrospective study was to define those patients who
      would benefit most from it. One hundred and twenty-one first PGD-AS cycles for
      recurrent IVF failure were analysed. The aneuploidy rate, 'no embryo transfer'
      rate, live birth rate per embryo transfer and implantation rate were respectively
      48.3, 22.3, 29.7 and 19.5%. A multivariate logistic regression analysis gave us a
      predictive model demonstrating that to have a 90% probability of having an embryo
      transfer after PGD-AS, the patient should have at least 10 mature oocytes, eight
      normally fertilized oocytes and six embryos for biopsy. This study suggests that
      most patients with recurrent IVF failure may benefit from PGD-AS. Future studies,
      however, should more strictly define this heterogeneous group of patients, so
      that comparison is easier.

PMID- 16569325
TI  - Laparoscopic evaluation of infertile patients with chronic pelvic pain.
AB  - In this study over a 10-year period, 1584 patients complaining of infertility of
      more than 1 year duration were evaluated for their laparoscopic findings in
      relation to the presence or not of chronic pelvic pain (CPP). Infertility was the
      only complaint in 1215 cases (group 1), whereas 369 patients complained of
      infertility and CPP (group 2). All cases underwent routine infertility
      investigation and pelvic ultrasonography, followed by diagnostic laparoscopy,
      with infertility-only cases acting as a control group. At laparoscopy 76.7% of
      patients with CPP were found with pelvic pathology, compared with only 42.6% of
      cases without CPP (P < or = 0.0001). Omental-abdominal wall adhesions, advanced
      endometriosis, endometriomas with adhesions, pelvic venous congestion, and
      hydrosalpinges with pelvic adhesions were significantly more frequent in cases
      with CPP. Dysmenorrhoea was the most frequent type of CPP. Cases with CPP and a
      negative laparoscopy were further investigated using a multidisciplinary
      approach. In conclusion, chronic pelvic pain can be the result of several pelvic
      pathologies. Infertile patients with CPP are much more frequently found with an
      abnormal pelvis in comparison with cases without CPP. Laparoscopy is an
      invaluable diagnostic tool especially for symptomatic patients and should be used
      early in their diagnostic infertility work-up.

PMID- 16569327
TI  - Screening for chromosomal abnormalities in 2650 infertile couples undergoing
      ICSI.
AB  - Chromosomal abnormalities are the major contributor to the genetic risks of
      infertility treatment associated with intracytoplasmic sperm injection (ICSI).
      The study objective was to assess prospectively the frequency of chromosomal
      aberrations in couples undergoing ICSI. A total of 2650 infertile couples (5300
      patients) underwent chromosome analysis before undergoing ICSI in the Egyptian
      IVF-ET Centre. Heparinized blood samples were cultured, harvested and banded
      according to standard methods. Overall, 96.94% of the patients studied
      (5138/5300) had a normal karyotype, while the remaining 162 patients (3.06%) had
      an abnormal karyotype. Male patients constituted the majority of abnormalities;
      138 males (85.19%) and 24 females (14.81%). These chromosomal aberrations
      included 117 cases (2.2%) of sex chromosome abnormalities; 113 males and four
      females. Forty-five patients (0.85%) had autosomal aberrations; 25 of them were
      males and 20 were females. The current data show that chromosomal abnormalities
      affect 3.06% of infertile patients, and occur in both sexes, but more
      predominantly in males undergoing ICSI for male factor infertility. It is
      recommended that chromosomal analysis be performed before undergoing ICSI, to
      identify patients who can be offered preimplantation genetic diagnosis.

PMID- 16569328
TI  - Sibling oocyte submission to IVF and ICSI in unexplained infertility patients: a
      potential assay for gamete quality.
AB  - In order to reduce total fertilization failure in unexplained infertility,
      sibling oocytes were submitted to both conventional IVF and intracytoplasmic
      sperm injection (ICSI). Two groups of ICSI embryos were compared in unexplained
      infertility patients: those derived from ICSI when IVF had failed to fertilize,
      and those derived from ICSI while their sibling oocytes were fertilized by IVF.
      The outcome of oocytes fertilized exclusively by ICSI (essential ICSI, n = 749)
      was compared with those fertilized both by IVF and ICSI (non-essential ICSI, n =
      957) in all IVF patients treated for unexplained infertility at the Hadassah
      Hospital (1999-2002). The latter group was further subdivided into ICSI and IVF
      embryos. Total fertilization rate was 54%. Fertilization rates by ICSI were lower
      in the essential ICSI compared with the non-essential ICSI group, at 65 and 73%
      (P < 0.025). Pregnancy rates per embryo transfer in the essential ICSI group
      (49%), ICSI derived embryos group (55%) and IVF derived embryos (44%) from the
      non-essential ICSI group, were similar. Implantation rates were lower in the
      essential ICSI group as compared with the non-essential ICSI group (21 versus 32%
      respectively; P < 0.05) and 26% for IVF embryos. In conclusion, essential ICSI
      was associated with lower fertilization and implantation rates.

PMID- 16569329
TI  - HIV seroconversion in a woman preparing for assisted reproduction: an inherent
      risk in caring for HIV-serodiscordant couples.
AB  - A woman preparing to undergo IVF and intracytoplasmic sperm injection to avoid
      horizontal viral transmission of HIV from her seropositive husband was discovered
      to be HIV seropositive, presumably secondary to a condom break or unprotected
      intercourse. Had this event occurred after treatment, the sperm-washing technique
      used to avoid infection would have undoubtedly been called into question. Nearly
      all HIV-serodiscordant couples are sexually active and therefore at risk for
      transmitting infection, either due to improper condom use or unprotected
      intercourse. Physicians willing to treat HIV-serodiscordant couples must accept
      the inevitability of viral transmission in occasional individuals. Furthermore,
      it should not be presumed that all patients who experience seroconversions after
      either intrauterine insemination or IVF procedures do so as a result of
      inadequacies in the sperm preparation technique.

PMID- 16569330
TI  - Role of p53 codon 72 polymorphism in recurrent pregnancy loss.
AB  - Recurrent pregnancy loss (RPL) has been associated with low expression of
      apoptosis-and angiogenesis-related genes. The p53 tumour suppressor gene has been
      shown to induce apoptosis and angiogenesis. Recently, a low increased frequency
      of a p53 codon 72 polymorphism has been reported among women experiencing RPL.
      This study investigated the prevalence of p53 codon 72 polymorphism among women
      with a history of RPL, to determine whether this polymorphism may serve as a risk
      factor for miscarriage. Buccal swabs were obtained from 205 women with a history
      of two or more consecutive spontaneous abortions and 25 women with at least two
      live births and not more than one elective abortion. DNA was extracted from the
      buccal swabs and PCR amplification of p53 arginine(Arg)72 and proline(Pro)72
      variants was performed. The frequency of homozygous Arg and Pro or heterozygous
      Arg/Pro genotypes among RPL patients and controls were not significantly
      different. No significant differences in allelic frequencies of p53 were
      observed. In addition, the allelic frequencies between controls and those
      previously reported were the same. It is concluded that p53 codon 72
      polymorphisms do not serve as a susceptibility factor affecting the chances of
      miscarriage in an unselected population.

PMID- 16569332
TI  - Towards better quality research in recurrent implantation failure: standardizing
      its definition is the first step.
AB  - Recurrent implantation failure is a frustrating condition for clinicians and
      patients alike. The number of potential therapies offered to patients in order to
      overcome this problem is increasing, and more research is needed to establish
      which of those treatment options is truly beneficial. Improved understanding of
      their value is more likely if the same definition of recurrent implantation
      failure is used across future studies. In this article, the inconsistency present
      in current literature is examined and the case is argued for a standardized
      definition for the condition.

PMID- 16569333
TI  - The mathematician gynaecologist.

PMID- 16569334
TI  - The Mary Magdalene Project.

PMID- 16569335
TI  - Central data collection on PGD and screening.

PMID- 16569336
TI  - Economic evaluations in healthcare: reply to comments.

PMID- 16569338
TI  - Gender selection of embryos after PGD for other independent medical reasons--a
      viewpoint from Singapore.

PMID- 16569339
TI  - Growth factor receptors in hematopoietic stem cells: EPH family expression in
      CD34+ and CD133+ cell populations from mobilized peripheral blood.
AB  - Cell-surface antigen expression of hematopoietic stem cells has a crucial role in
      characterizing cell subpopulation with distinct functional properties. The Eph
      receptors are the largest receptor tyrosine kinase family being involved in
      processes like vascular remodelling during development and physiological and
      pathological angiogenesis. Some Eph/Ephrin members are expressed in hematopoietic
      cells. The ability to isolate purified cell populations co-expressing CD34 and
      CD133 antigens as most commonly used markers for identification of hematopoietic
      progenitors has provided the opportunity to identify their surface-receptor
      profile. As positively expressed CD34 and CD133 cells take place not only in
      hematopoietic but also in endothelial differentiation, we aimed to define the
      Eph/Ephrin characteristic of these cells and relate these findings to new therapy
      strategies. Positive selections of CD34 and CD133 cells from PBPC in lymphoma
      patients were performed using magnetic beads and AutoMACS (Miltenyi Biotec)
      device. The purity of isolated cells was tested by flow cytometry.
      Immunocytochemistry was used to assess the Eph/Ephrin expression profile of
      positively selected samples. Our study revealed that all samples (10 from CD34+
      and 8 from CD133+ cells) expressed one or more of Eph/Ephrin antigens in
      different proportions. All CD34+ cell samples, and 6 of 8 in the CD133+ cell
      fraction were strongly immunoreactive for EphA2. EphB2 was strongly expressed in
      all CD133+ cases, but 50% of the CD34 positive group lacked or weakly expressed
      this receptor. EphB4 was negative in 9 of 10 CD34+ cases and in all CD133+ cells.
      Thus, we have shown the surface marker profile of positively selected CD34 and
      CD133 cells in leukapheresis samples from lymphoma patients with regard to
      Eph/Ephrin receptors and discussed their biological clinical potential.

PMID- 16569340
TI  - Increased levels of IGF-1 and beta2-microglobulin in epithelial lining fluid of
      preterm newborns developing chronic lung disease. effects of rhG-CSF.
AB  - Insulin-like growth factor-1 (IGF-1) is involved in regulating the Th-1/Th-2
      balance, favoring the development of the Th-2 compartment which enhances
      fibrosis, one of the main characteristics of Chronic Lung Disease (CLD) in
      premature newborns. Limited data is available concerning a possible association
      between early epithelial lining fluid (ELF) concentrations of IGF-1 (total and
      free forms), IGF-binding protein-3 (IGFBP-3), beta2-microglobulin and subsequent
      development of CLD in preterm neonates. If neutropenic, preterm neonates are
      frequently treated with recombinant human granulocyte colony stimulating factor
      (rhG-CSF). The objective of the study was to correlate ELF concentrations of IGF
      1 and beta2 microglobulin during the first week of life both in non-neutropenic
      and in rhGCSF-treated neutropenic preterm neonates, with subsequent development
      in CLD. Thirty preterm neonates with Respiratory Distress Syndrome (6 with
      neutropenia) were studied. Eleven out of 24 non-neutropenic preterm infants (46%)
      and all of the six neutropenic subjects (100%) developed CLD. With the exception
      of first day values, there was a clear similarity in the behaviors of assayed
      molecules between non-neutropenic and neutropenic patients developing CLD. Non
      neutropenic patients without CLD showed significantly lower values of free IGF-1
      and beta2M both on days 1 and 3. Total IGF-I and cell counts were different only
      on the 3rd day. CONCLUSIONS: 1) the mechanisms leading to CLD might be mediated
      by high levels of IGF-family molecules soon after birth 2) beta2M could be a
      marker of increased bronchoalveolar lavage fluid cellularity with potential
      inflammatory properties 3) G-CSF treatment induces an increased synthesis of IGF
      1 molecules by cells recruited in the lung, with possible enhancement of the
      fibrogenic mechanisms.

PMID- 16569341
TI  - Interleukin-31: a new cytokine involved in inflammation of the skin.

PMID- 16569342
TI  - Fibromyalgia--new concepts of pathogenesis and treatment.
AB  - Fibromyalgia (FMS) is a debilitating disorder characterized by chronic diffuse
      muscle pain, fatigue, sleep disturbance, depression and skin sensitivity. There
      are no genetic or biochemical markers and patients often present with other
      comorbid diseases, such as migraines, interstitial cystitis and irritable bowel
      syndrome. Diagnosis includes the presence of 11/18 trigger points, but many
      patients with early symptoms might not fit this definition. Pathogenesis is still
      unknown, but there has been evidence of increased corticotropin-releasing hormone
      (CRH) and substance P (SP) in the CSF of FMS patients, as well as increased SP,
      IL-6 and IL-8 in their serum. Increased numbers of activated mast cells were also
      noted in skin biopsies. The hypothesis is put forward that FMS is a neuro
      immunoendocrine disorder where increased release of CRH and SP from neurons in
      specific muscle sites triggers local mast cells to release proinflammatory and
      neurosensitizing molecules. There is no curative treatment although low doses of
      tricyclic antidepressants and the serotonin-3 receptor antagonist tropisetron,
      are helpful. Recent nutraceutical formulations containing the natural anti
      inflammatory and mast cell inhibitory flavonoid quercetin hold promise since they
      can be used together with other treatment modalities.

PMID- 16569343
TI  - Hormone refractory prostate cancer (HRPC): present and future approaches of
      therapy.
AB  - The mainstay of therapy for patients with advanced prostate cancer still remains
      androgen deprivation, although response to this is invariably temporary. Most of
      the patients develop hormone-refractory disease resulting in progressive clinical
      deterioration and, ultimately, death. Until recently there has been no standard
      chemotherapeutic approach for hormone refractory prostate cancer (HRPC), the
      major benefits of chemotherapy being only palliative. The studies combining
      mitoxantrone plus a corticosteroid demonstrated that chemotherapy could be given
      to men with symptomatic HRPC with minimal toxicity and a significant palliation
      could be provided. Recently, results from 2 phase III randomized clinical trials
      demonstrating that a combination of docetaxel plus prednisone can improve
      survival in men with HRPC have propelled docetaxel-based therapy into the
      forefront of treatment options for these patients as the new standard of care.
      There is a promising activity of new drug combinations such as taxanes plus vinca
      alkaloids; bisphosphonates are assuming a prominent role in prostate therapy
      through their ability to prevent skeletal morbidity. Combinations of classic
      chemotherapeutic agents and biological drugs began to be tested in phase II-III
      trials and the first results appear interesting. This article focuses on
      combinations recently evaluated or under clinical development for the treatment
      of HRPC.

PMID- 16569344
TI  - Shear stress modulates the expression of thrombospondin-1 and CD36 in endothelial
      cells in vitro and during shear stress-induced angiogenesis in vivo.
AB  - Binding of thrombospondin-1 (TSP-1) to the CD36 receptor inhibits angiogenesis
      and induces apoptosis in endothelial cells (EC). Conversely, matrix-bound TSP-1
      supports vessel formation. In this study we analyzed the shear stress-dependent
      expression of TSP-1 and CD36 in endothelial cells in vitro and in vivo to reveal
      its putative role in the blood flow-induced remodelling of vascular networks.
      Shear stress was applied to EC using a cone-and-plate apparatus and gene
      expression was analyzed by RT-PCR, Northern and Western blot. Angiogenesis in
      skeletal muscles of prazosin-fed (50 mg/l drinking water; 4 d) mice was assessed
      by measuring capillary-to-fiber (C/F) ratios. Protein expression in whole muscle
      homogenates (WMH) or BS-1 lectin-enriched EC fractions (ECF) was analyzed by
      Western blot. Shear stress downregulated TSP-1 and CD36 expression in vitro in a
      force- and time-dependent manner sustained for at least 72 h and reversible by
      restoration of no-flow conditions. In vivo, shear stress-driven increase of C/F
      in prazosin-fed mice was associated with reduced expression of TSP-1 and CD36 in
      ECF, while TSP-1 expression in WMH was increased. Down-regulation of endothelial
      TSP-1/CD36 by shear stress suggests a mechanism for inhibition of apoptosis in
      perfused vessels and pruning in the absence of flow. The increase of extra
      endothelial (e.g. matrix-bound) TSP-1 could support a splitting type of vessel
      growth.

PMID- 16569345
TI  - c-MYC deregulation is involved in melphalan resistance of multiple myeloma: role
      of PDGF-BB.
AB  - Oncogenes are important regulators of cancer growth and progression and their
      action may be modulated by proteins of the growth factor family, such as
      angiogenic cytokines, known to be strongly involved in neoplastic evolution.
      Reciprocal interactions between oncogenes and angiogenic modulators may
      represent, in haematological neoplasms, including multiple myeloma (MM), a
      possible mechanism of drug resistance. The aim of this work is to investigate in
      vitro and in vivo whether or not c-myc deregulation is involved in the melphalan
      resistance elicited by myeloma patients and consequently to clarify the role of
      the angiogenic factor PDGF-BB in modulating c-myc protein expression. Fifty-one
      MM patients on chemotherapy with melphalan were analyzed for structural
      alterations of the c-myc gene, c-Myc protein expression, as well as for serum
      PDGF-BB release. For the in vitro study, two M14-derived established cell clones,
      differing for the c-Myc protein expression (c-Myc low -expressing or
      constitutively expressing clones) were used. Our results show that PDGF-BB is
      able to up-regulate Myc expression and reduce melphalan sensitivity of tumor cell
      clones, constitutively expressing c-myc gene product. In addition, down
      regulation of c-Myc protein induces the expression of PDGF-beta receptor
      molecules and reduces PDGF-BB release. In agreement with these results, in vivo
      data show that melphalan-resistant MM patients present overexpressed c-Myc
      protein and higher serum PDGF-BB receptor levels compared to minor responding
      patients.

PMID- 16569346
TI  - The expression of CD154 by Kaposi's sarcoma cells mediates the anti-apoptotic and
      migratory effects of HIV-1-TAT protein.
AB  - Kaposi's sarcoma (KS) is a malignancy associated to conditions of immune system
      impairment such as HIV-1 infection and post-transplantation therapy. Here we
      report that HIV-1-Tat protein, at concentrations well below those detected in
      AIDS patients, up-regulates the expression of both CD40 and CD154 on KS cells.
      This occurred also in the presence of vincristine, that at doses shown to induce
      apoptosis decreased the expression of both CD40 and CD154 on KS cells. The
      treatment with a soluble CD40-muIg fusion protein (CD40 fp) that prevents the
      binding of CD154 with cell surface CD40, as well as the transfection with a
      vector for soluble CD40 (KS sCD40), decreased the anti-apoptotic effect of Tat.
      Moreover, Tat-induced motility of KS cells was inhibited by soluble CD40 fp. Tat
      also enhanced the expression of intracellular proteins known to transduce signals
      triggered by CD40 engagement, in particular TRAF-3. Tat as well as soluble CD154
      (sCD154) prevented vincristine-induced reduction of TRAF-3 in KS cells
      transfected with a vector for neomycin resistance (KS psv-neo), but not in KS
      sCD40. Immunoprecipitation studies showed that Tat induced CD40 / TRAF-3
      association and that this binding was abrogated upon the incubation with the
      soluble CD40 fp. These data suggest that Tat activates the CD40-CD154 pathway by
      enhancing the membrane expression of CD40 and in particular of CD154, and by
      activating the TRAF-3-dependent signaling pathway of CD40. These findings
      indicate that the CD40-CD154 pathway mediates the anti-apoptotic and migratory
      effects of HIV-1- Tat, suggesting the potential therapeutic benefits of blocking
      CD40 activation in HIV-1-associated KS.

PMID- 16569347
TI  - Soluble CD30 and lymphocyte activation gene-3 (CD223), as potential serological
      markers of T helper-type cytokine response induced by acellular pertussis
      vaccine.
AB  - T cell responses are involved in vaccine-induced immunity to pertussis but no
      easy-to-monitor, serological markers are available to assess these responses. The
      lymphocyte activation gene-3 (CD223) molecule is present on, and released by,
      activated T helper (Th) 1 cells, whereas CD30 molecules have been associated with
      Th2 immune responses. Starting from the recent knowledge of the cytokine profile
      induced by pertussis vaccination, we examined the levels of soluble (s)CD223 and
      sCD30 proteins in child recipients of acellular pertussis (aP) and diphtheria
      tetanus (DT) vaccines and in children receiving DT vaccine only, as control. The
      correlation of the two proteins with specific antibody and T cell responses was
      assessed. The main findings are: i) sCD223 and sCD30 levels are inversely
      related, suggesting that the two markers are the expression of different and
      counter-regulated T-cell responses; ii) sCD30 level correlated with induction of
      T cell proliferation to pertussis vaccine antigens and antibody response to
      pertussis toxin. Overall, sCD30 and sCD223 levels seem to be promising candidate
      markers to assess the induction of Th-type responses in vaccine recipients.

PMID- 16569348
TI  - Expression of HECA-452 in parapsoriasis and mycosis fungoides.
AB  - We have investigated the HECA-452 expression in large plaque parapsoriasis (PP)
      and mycosis fungoides (MF) patients, evaluating the potential role of this
      biomarker in both cutaneous disorders. Skin specimens from 72 PP and 61 MF
      patients were selected in this study. We compared their actual histological
      diagnosis with their previous diagnosis and we found that all 72 PP patients had
      the same diagnosis as before (stable PP), while 26 out of 61 MF had a previous PP
      histological diagnosis (evolving PP). Our results show an increased expression of
      HECA-452 in MF compared to PP (p<0.01). Furthermore, evolving PP showed a
      significantly higher level of HECA-452 than stable PP (p<0.05). We conclude that
      HECA-452 expression increases during the natural history of Mycosis Fungoides.
      HECA-452 could be used as a biomarker for MF and predict which PP evolves to MF.

PMID- 16569349
TI  - Chlamydia pneumoniae in asymptomatic carotid atherosclerosis.
AB  - We evaluated, in 415 patients with asymptomatic carotid atherosclerosis: (i) the
      prevalence of C. pneumoniae DNA in atherosclerotic carotid plaques and peripheral
      blood mononuclear cells (PBMC); (ii) the distribution of C. pneumoniae in
      atherosclerotic carotid plaques and PBMC from the same patients; (iii) the
      correlation between circulating anti-chlamydial antibodies and the presence of C.
      pneumoniae DNA. Overall, 160 atherosclerotic carotid plaques and 174 PBMC
      specimens from patients with asymptomatic carotid atherosclerosis were examined
      by ompA nested touchdown PCR for presence of C. pneumoniae. In addition, C.
      pneumoniae DNA was detected in 81 specimens of atherosclerotic carotid plaque and
      PBMC obtained from the same patients. C. pneumoniae DNA was found in 36.9% of
      atherosclerotic carotid plaques and in 40.2% of PBMC specimens examined (P=NS).
      With regard to 81 patients, C. pneumoniae DNA was detected in 27.2% of
      atherosclerotic carotid plaques and in 44.4% of PBMC specimens(P=0.05). In 18
      patients, the presence of C. pneumoniae DNA in PBMC specimens and atherosclerotic
      carotid plaques coincided (P=0.005). No statistically significant association was
      found between anti-C. pneumoniae antibodies (IgG and IgA) and positive PCR
      results. In conclusion, our results suggest that the detection of C. pneumoniae
      DNA in PBMC specimens seems to be a first-choice method to identify the patients
      at risk for endovascular chlamydial infection.

PMID- 16569350
TI  - T cell assessment in allergic drug reactions during the acute phase according to
      the time of occurrence.
AB  - Allergic drug reactions can be classified as immediate, accelerated or delayed.
      This classification usually correlates with the mechanism involved: immediate
      reactions are IgE mediated and delayed reactions are T cell dependent. We
      analyzed lymphocyte involvement in patients with these reactions by determining
      cell subpopulations, activation state and skin homing receptor expression (CLA)
      in blood and skin. Patients with immediate, accelerated and delayed reactions
      were evaluated during the acute phase and after resolution. Controls taking drugs
      were included. Phenotypic immunofluorescence analysis was done by flow cytometry
      in peripheral blood, and by immunohistochemistry in skin for delayed reactions.
      Forty-six patients were included, 17 with immediate reactions, 10 accelerated and
      19 delayed. At the acute phase CLA was significantly increased in delayed
      reactions and HLA-DR in all three types of reaction. In the severest delayed
      reactions, Steven-Johnson/Lyell syndromes, the CD4 subsets were increased in
      peripheral blood and skin compared to maculopapular exanthemas and urticaria and
      HLA-DR when compared with urticaria. In maculopapular exanthemas CLA was
      significantly increased in peripheral blood and skin compared to urticaria and
      the severe reactions. We found that T-cells are implicated, besides delayed
      reactions, in immediate and accelerated reactions. In delayed reactions there is
      a parallelism between results found in skin and peripheral blood with a higher
      participation of CD4+ cells the more severe the reaction.

PMID- 16569351
TI  - Inhaled tobramycin in children with acute bacterial rhinopharyngitis.
AB  - Antibiotic abuse for treating rhinopharyngitis induces the occurrence of
      resistant bacteria. As topical drugs might reduce this phenomenon, the aims of
      our study were to evaluate inhaled tobramycin in children with acute bacterial
      rhinopharyngitis and to compare it with oral amoxicillin/clavulanate. The trial
      was conducted as randomized, parallel group and double blind. Children, aged 3-6
      years, with acute bacterial rhinopharyngitis were treated with 15 mg of
      aerosolized tobramycin (Group A) or 50 mg/Kg of amoxicillin/clavulanate (Group B)
      twice daily for 10 days. The following parameters were assessed: nasal
      obstruction, mucopurulent rhinorrhea, post-nasal drip, adenoidal hypertrophy,
      tympanic inflammation, tympanogram, rhinomanometry and cultures. Of 416 patients
      screened, 311 children (178 females and 133 males), median age 4.5 years,
      completed the study: 156 in Group A and 155 in Group B. Both treatments improved
      all parameters (p<0.01 for all). Intergroup analysis showed that inhaled
      tobramycin induced a better improvement versus amoxicillin/clavulanate concerning
      nasal obstruction (p<0.05), adenoidal hypertrophy (p<0.01), tympanic inflammation
      (p<0.01), rhinomanometry (p<0.01) and cultures (p<0.05). In conclusion, inhaled
      tobramycin may represent a valid treatment for acute bacterial rhinopharyngitis
      in children, as it is effective, safe, economic and simple to use.

PMID- 16569352
TI  - Sublingual reactivity to rBET V1 and rPHL P1 in patients with oral allergy
      syndrome.
AB  - Oral Allergy Syndrome (OAS) in patients with pollen-induced rhinoconjunctivitis
      is caused by specific IgE recognizing cross-reacting epitopes of fruits and
      plants, which were clearly shown in vitro, but failed to be demonstrated in vivo
      by cross-challenges in the target organs. Considering the hypothesis of
      degradation of such epitopes in natural extracts, challenges with recombinant
      pollen allergens were done to evaluate the reactivity of the oral mucosa in OAS
      patients. Seventeen patients with OAS and rhinitis from birch (10) and grass
      pollen (7) and 10 non-atopic controls were studied by skin prick tests (SPT),
      allergen specific nasal challenges (ASNC) and allergen specific sublingual
      challenges (ASSC) with birch and timothy extracts and with rBet v1 and rPhl p1 at
      increasing concentrations from 1 to 1000 mcg/ml. None of the healthy subjects in
      the control group had any positive test for birch and timothy extracts or for
      recombinant allergens. In the OAS group the following results were observed: SPTs
      with recombinant allergens were positive in all patients, mostly at 10 mcg/ml
      concentration; ASNC with rBet v1 were positive in all patients, mostly at 100
      mcg/ml; ASSC with natural pollen extracts were positive in only 2 of 17 patients,
      but in 15 of 17 with rBet v1 and rPhl p1, mostly at 500 mcg/ml and 1000 mcg/ml.
      ASSC with rBet v1 and rPhl p1 were positive with a mean concentration of 677 and
      533 mcg/ml, respectively. The results of sublingual challenges with rBet v1 and
      rPhl p1 showed the in vivo cross-reactivity between pollens and foods in patients
      with OAS, but high concentrations of the recombinant allergens were needed to
      reproduce oral symptoms, thus explaining the failure of challenges performed with
      natural extracts, which have concentrations of major allergens lower than 50
      mcg/ml. This indicates that sublingual mucosa is much less reactive to allergens
      than other surfaces, such as skin and nasal mucosa, probably because of its
      anatomic and immunologic peculiarity.

PMID- 16569353
TI  - Thyroid hormone and thyrotropin regulate intracellular free calcium
      concentrations in human polymorphonuclear leukocytes: in vivo and in vitro
      studies.
AB  - Intracellular free calcium concentrations (Ca++i) were studied in
      polymorphonuclear leukocytes (PMNs) from 13 athyreotic patients who had been
      previously treated by total thyroidectomy and radioiodine therapy for
      differentiated thyroid carcinoma, and from age- and sex-matched euthyroid healthy
      controls. Patients were studied twice, when hypothyroid (visit 1) and after
      restoration of euthyroidism by L-T4 TSH-suppressive therapy (visit 2). PMNs from
      patients at visit 1 had significantly lower resting (Ca++)i levels compared to
      both visit 2 and controls. Values at visit 2 did not differ from those of the
      controls. Stimulus-induced (Ca++)i rise was also significantly blunted at visit 1
      and normalized at visit 2, possibly through a differential contribution of
      distinct intracellular Ca++ stores, as suggested by the response pattern to the
      chemotactic agent, N-formyl-Met-Leu-Phe (fMLP), to the selective SERCA pump
      inhibitor, thapsigargine, and to the mitochondrial uncoupler, carbonyl cyanide p
      trifluoromethoxyphenyl-hydrazone (FCCP). In vitro treatment of PMNs from healthy
      subjects with high TSH concentrations impaired intracellular Ca++ store function.
      Both resting (Ca++)i levels and fMLP-induced (Ca++)i rise increased in the
      presence either of low-concentration TSH or of T4, but effects of TSH and T4 were
      not additive. T3, rT3, and TRIAC had no effect. In conclusion, this study
      provides evidence for a direct relationship between thyroid status and (Ca++)i
      homeostasis in human PMNs, mainly related to direct actions of TSH and T4 on
      these cells.

PMID- 16569354
TI  - Angiogenic molecules in Hodgkin's disease: results from sequential serum
      analysis.
AB  - Increased angiogenic activity has been demonstrated in lymphoproliferative
      diseases including Hodgkin's disease. In the current study, the levels of
      circulating angiogenic molecules in 60 Hodgkin's patients were determined prior
      to and after treatment and correlated to disease stage and prognostic score.
      Hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF),
      interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were increased
      in Hodgkin's patients in comparison to healthy controls (p<0.001). Angiogenin and
      angiopoietin-2 levels did not differ from controls. HGF, VEGF, TNF-alpha and
      angiogenin decreased significantly in Hodgkin's patients after standard treatment
      (p<0.001 for HGF, p<0.05 for VEGF, TNF-alpha and angiogenin). Furthermore, HGF
      and TNF-alpha increased with advancing stage of disease (p<0.05). HGF and VEGF
      correlated significantly with IL-6 (r=0.56, p<0.0005 and r=0.57, p<0.001
      respectively). In conclusion, Hodgkin's disease displays an angiogenic activity
      as depicted by the increased serum levels of a number of angiogenic cytokines.
      HGF seems to be the prominent molecule in Hodgkin's disease, which may be used to
      monitor the disease status and the response to treatment.

PMID- 16569355
TI  - Tumor infiltrating lymphocytes in uveal melanoma: a link with clinical behavior?
AB  - Experimental and clinical evidence indicate that immunological mechanisms might
      be important in the clinical course of uveal malignant melanoma (UMM). We
      analyzed the amount and phenotype of tumor infiltrating lymphocytes (TIL) and the
      expression of the apoptosis-inducing molecule Fas and its ligand, FasL, on tumor
      cells and TIL in a selected series of UMM with the aim to establish if a
      correlation between their expression and the clinical behavior of UMM exists. TIL
      phenotype and Fas/FasL expression were evaluated by immunohistochemistry in 61
      cases of formalin-fixed, paraffin-embedded UMM. Results were compared with the
      follow-up data of patients. Most of the UMM showed a prevalence of CD8+ CD3+ T
      lymphocytes, or CD4+ and CD8+ cells in equal amounts. UMM showed a variable
      expression of FasL, ranging from 0 to > 40% of neoplastic cells. Fas was always
      expressed in TIL, although with a variable extent. A subgroup of UMM showed in
      TIL a strongly reduced or even absent expression of TCR zeta-chain, involved in
      activation of T-lymphocytes. This subgroup was characterized by a worse outcome.
      We hypothesized that an impaired cytotoxic immune response due to the loss of the
      zeta-chain expression plays a primary role in the biological course of UMM. Our
      results indicate that the overcoming of the impairment of TCR function may
      represent a prerequisite for the development of new therapeutic strategies for
      managing UMM, suggesting that elimination of tumor cells may be possible by
      activation of cytotoxic cells present within ocular melanomas.

PMID- 16569356
TI  - Altered vessel signalling molecules in subjects with Downs syndrome.
AB  - Downs syndrome (DS) is the most frequent human chromosomal abnormality and is
      associated with mental retardation. Some evidence indicates that certain
      inflammatory molecules may be increased in DS. Proinflammatory and vasoactive
      molecules in the blood of non demented subjects with DS were measured in the
      present investigation. Plasma levels of interleukin-6 (IL-6), vascular
      endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1) and
      C reactive protein (CRP) were measured in child (2-14 years), adult (20-50 yrs)
      and elderly (> 60 yrs) DS subjects. Increased plasma levels of IL-6 and MCP-1
      were present in DS. Plasma levels of VEGF were increased only in DS adults.
      Positive linear correlation between IL-6 and MCP-1 levels was present. However,
      no subclinical inflammation was apparent in DS, since neopterin and CRP levels
      were within the normal range. An altered regulation of these molecules might
      interfere with some processes involved in cognitive performances of DS subjects.

PMID- 16569357
TI  - Exploiting the plant secretory pathway to improve the anticancer activity of a
      plant-derived HPV16 E7 vaccine.
AB  - The human papillomavirus 16 (HPV16) E7 oncoprotein can be considered a "tumor
      specific antigen", and therefore it represents a promising target for a
      therapeutic vaccine against HPV-associated tumors. Efficient production of E7
      protein with a plant-based transient expression system has been already described
      and it was demonstrated that E7-containing crude plant extracts confer partial
      protection against tumor challenge in a mouse model system. Before adopting the
      plant-based system as a cost-effective method for the production of an E7-based
      anti-cancer vaccine, some aspects, such as the oncoprotein yield, need further
      investigation. In the present study, we report the transient expression, mediated
      by a potato virus X (PVX)-derived vector, of the E7 protein targeted to the
      secretory system of Nicotiana benthamiana plants by using a plant-derived signal
      sequence. Targeting the antigen to the secretory pathway enhanced the E7 protein
      expression levels about five-fold. Mice immunized by s.c. administration with
      crude foliar extracts containing E7 showed strong stimulation of cell-mediated
      immune response after five boosters, as detected by ELISPOT. After challenging
      with the E7-expressing C3 tumor cells, tumor growth was completely inhibited in
      80% of the vaccinated animals and a drastic reduction of tumor burden was
      observed in the remaining tumor-affected mice. These data demonstrate that, by
      enhancing E7 yield, it is possible to improve the anti-cancer activity of the
      plant-based experimental vaccine and open the way for a large-scale production of
      the E7 protein which could be purified or used as in planta formulation, also
      suitable for oral therapeutic vaccination.

PMID- 16569359
TI  - Detection of human papillomavirus DNA, p53 and ki67 expression in penile
      carcinomas.
AB  - Our study is aimed at evaluating the presence of p53 and Ki67 expression by
      immunohistochemistry in a series of 11 paraffin-embedded penile carcinomas. We
      also investigated the presence of Human Papillomavirus (HPV) DNA in these tumours
      and performed an accurate typing by DNA sequencing on positive samples.
      Immunohistochemistry (IHC) was performed with the anti-p53 and Ki67 mouse
      monoclonal antibodies. DNA extracted from small sections of each specimen was
      submitted to amplification with HPV specific general primers; PCR products of the
      proper length were purified and sequenced. IHC demonstrated nuclear accumulation
      of mutated p53 and Ki 67 expression in 10/11 tumour samples (90.9%). The
      prevalence of HPV DNA was 72.7%; the most prevalent type was HPV16. Sequencing
      analysis revealed the presence of HPV53 (12.5%), HPV18 (25%) and HPV16 (62.5%).
      Out of the p53 or Ki67 positive carcinomas the percentage of HPV positives was
      80% and 70% respectively. Our results indicate that penile carcinoma is
      frequently associated to high risk HPV and with diffuse p53 and Ki67 expression.

PMID- 16569358
TI  - Serological markers of pulmonary tuberculosis and of response to anti
      tuberculosis treatment in a patient population in Guinea.
AB  - The aim of the study was to evaluate serological correlates of active
      tuberculosis and of response to antituberculosis treatment in a cohort of HIV
      negative patients with pulmonary tuberculosis studied at diagnosis and during
      treatment at the Service de Pneumo-Phtisiologie, Centre Hospitalier-Universitaire
      Ignace Deen, Conakry, Republic of Guinea. Two similar cohorts of HIV-negative
      healthy households of patients and healthy community controls were included in
      the study. Plasma samples were obtained from 168 untreated tuberculosis patients,
      167 healthy household controls, and 168 healthy community controls. Serial plasma
      samples were also obtained from the tuberculosis patients at 2 and 8 months after
      initiation of chemotherapy. IgG antibody levels were measured by an enzyme-linked
      immunosorbent assay (ELISA) using ten purified M. tuberculosis antigens. ELISA
      results were analysed by comparing geometric means of data. Of the ten antigens
      tested, five (14kDa Ag, 19kDa Ag, AlaDH, MS, and MPT83) elicited similar antibody
      responses in untreated TB patients and controls. In contrast, levels of three
      antibodies (ESAT-6, LAM, and 38kDa Ag) were higher in untreated TB patients than
      in household or community controls (p<0.0001). Levels were higher in untreated
      patients than in community controls also for the anti-Rv2626c antibody (p =
      0.0001) and, at a lower significance level, for the anti-FdxA antibody (p<0.025).
      Antibody levels against ESAT-6 and Rv2626c decreased during therapy, while
      antibody levels to the 38 kDa antigen and LAM increased during therapy; FdxA
      antibody levels did not vary with treatment. Neither severity of presentation nor
      chest X-ray patterns affected levels of these antibodies before treatment. In
      contrast, after the 8-month therapeutic course, patients who presented with
      moderate/severe disease had higher levels of anti-ESAT-6, anti-FdxA, and anti
      38kDa antibodies than those of patients with mild disease onset. Patients with
      bilateral lung lesions had significantly higher anti-38kDa and anti-LAM levels,
      both at diagnosis and after 8-month treatment, than patients with lesions
      involving only one lung. Antibodies to alanine dehydrogenase and malate
      synthetase measured at initiation of treatment were higher in tuberculosis
      patients who subsequently failed therapy than in those who were cured. The main
      conclusions of the study are: a) plasma levels of antibodies to a number of M.
      tuberculosis represent serological correlates of active disease; b) these
      correlates are affected in an antigen-specific fashion by anti-tuberculosis
      treatment; c) particular serological markers may be predictive of treatment
      outcome.

PMID- 16569360
TI  - Detection of hepatitis C virus-RNA in saliva from chronically HCV-infected
      patients.
AB  - The possibility of the non-parenteral Hepatitis C Virus (HCV) transmission is
      supported by the demonstration that the actual virus is present in several body
      fluids, including saliva. From a review of the literature many investigators have
      found the presence of HCV-RNA in saliva, however, widely contrasting results
      emerge, with detection rates ranging from 0-100%. To further examine HCV salivary
      shedding, saliva samples were collected from 46 chronically HCV-infected patients
      and tested for HCV-RNA and occult blood. Quantification and genotyping of serum
      HCV-RNA were also carried out for each patient. HCV-RNA was detected in 39.13% of
      the saliva samples. The viral salivary shedding was significantly related to
      viraemia levels, serum viral genotype and the presence of salivary occult blood.
      Our findings indicate that the HCV salivary shedding occurs in about one third of
      HCV infected patients, but seem to suggest that it is unlikely when the serum
      viral genotype is 3a. Moreover, blood leakage into the oral cavity is possibly
      the main source of the salivary HCV-RNA. Although the occurrence of the viral
      salivary shedding does not necessarily mean that HCV transmission occurs by
      saliva, our results suggest the need for further investigations into the
      biological factors possibly involved in HCV mucosal transmission related to both
      the source and the exposed subjects.

PMID- 16569361
TI  - Once-weekly administration of high-dosage Etanercept in patients with plaque
      psoriasis: results of a pilot experience (power study).
AB  - Etanercept is a soluble tumour necrosis factor receptor fusion protein which is
      approved for the treatment of plaque psoriasis at the dose of either 25mg twice
      weekly (BIW) or, for the initial 12 weeks, 50mg BIW. Alternative dosing regimens
      have not been evaluated in psoriasis. In this study, we compare the efficacy and
      tolerability of two etanercept dosing regimens--50mg BIW and 100mg once weekly
      (OW)--for 12 weeks in 108 patients with moderate-to-severe recalcitrant
      psoriasis. Efficacy measures included Psoriasis Area and Severity Index (PASI),
      severity of pruritus recorded on a visual analogue scale (VAS) and the influence
      on quality of life assessed by means of Dermatology Life Quality Index (DLQI).
      Both etanercept regimens caused a significant change in all the efficacy
      parameters after 4 weeks and 12 weeks, at a comparable rate. At week 12, a PASI
      improvement of at least 50% from baseline (PASI 50) was achieved by 74% of
      patients treated with 50mg BIW and 78% of patients treated with 100mg OW. A PASI
      75 response was obtained in 54% and 50% of patients treated with 50mg BIW and
      100mg OW, respectively. Treatment was well tolerated with similar type and
      frequency of adverse events between the two groups.

PMID- 16569362
TI  - Cytokines in the nasal washes of children with respiratory syncytial virus
      bronchiolitis.
AB  - Although respiratory syncytial (RS) virus is the major cause of bronchiolitis and
      pneumonia in young children, the factors that regulate the associated lung
      inflammation have not been defined. The levels of interleukin (IL)10, IL-12, and
      interferon (IFN) were determined in the nasal wash samples from 20 infants with a
      clinical diagnosis of bronchiolitis, seven with confirmed RS virus infections and
      9 control children without respiratory illnesses. IL-10 levels were significantly
      higher in acute nasal wash samples (1-4 d post hospitalization) from RS virus
      infected infants than in convalescent samples from these children (14-21 d post
      hospitalization), from children with other forms of bronchiolitis and from
      control children. In contrast, only one RS virus-infected infant had detectable
      IL-12 in an acute nasal wash sample. IFN activity was not detected in any samples
      from RS virus-infected children. RS virus infection stimulates IL-10 expression
      but not IL-12 and IFN, possibly contributing to an ineffective cell-mediated
      immune response.

PMID- 16569363
TI  - Infliximab in recalcitrant severe atopic eczema associated with contact allergy.
AB  - Infliximab is an anti-tumour necrosis factor (TNF)-alpha chimeric monoclonal
      antibody which is effective in diseases associated with a T-helper (Th) 1
      response, such as rheumatoid arthritis, Crohn's disease and psoriasis. There are
      sporadic case reports of atopic dermatitis (AD) induced or precipitated by anti
      TNF-alpha therapy, which have been attributed to the switch towards Th2-mediated
      reactions. We report the case of a 30-year-old man with long-standing severe AD
      associated with contact allergy and poorly responding to conventional treatments.
      The use of infliximab resulted in a dramatic amelioration of AD lesions and
      pruritus, persisting at follow-up examinations over a 3-year period. Probably,
      the unexpected response to infliximab therapy in this case might be due to some
      peculiar features of AD in our patient (i.e. chronic-continuous course and
      concomitant contact allergy) which could have been responsible for a more
      preponderant recruitment of Th1 cells as compared to common forms of AD.

PMID- 16569364
TI  - Encrusted cystitis in an immunocompromised patient: possible coinfection by
      Corynebacterium urealyticum and E. coli.
AB  - Encrusted cystitis is a severe chronic inflammatory disease of the bladder
      characterized by excessively alkaline urine and calcifications within the bladder
      wall. A case of a 60 year-old man affected by systemic lupus erythematosus (SLE),
      which developed encrusted cystitis due to Corynebacterium urealyticum with E.
      coli co-infection, shows that the treatment of encrusted cystitis with a
      endoscopic debulking of the encrusted stones and an antimicrobial therapy
      specific for C. urealyticum often is not sufficient for the complete resolution
      of symptoms.

PMID- 16569365
TI  - Surveillance colonoscopy should be conducted in patients with colorectal
      Shistosomiasis even after successful treatment of the disease.

PMID- 16569367
TI  - Prevalence of secondary hematologic disorders in the antiphospholipid syndrome:
      impact on coagulation risk.
AB  - Hematologic abnormalities may occur in antiphospholipid antibody syndrome. The
      most common of these abnormalities is thrombocytopenia. The mechanism by which
      low platelet counts occur is not known but studies continue to elucidate the
      potential role of autoantibodies and cell surface markers. The risk for
      thrombosis in patients with thrombocytopenia does not appear to be related to the
      presence of thrombocytopenia itself. Innovative treatment with anti-CD20
      antibodies may be of benefit in reversing thrombocytopenia and treatment with
      splenectomy does not appear to increase the risk for subsequent thrombosis.
      Hemolytic anemia is associated with antiphospholipid antibodies as well, but the
      risk for thrombosis in patients with hemolytic anemia is not clearly elevated.
      Diagnostic features of disseminated intravascular coagulation may co-occur with
      the antiphospholipid syndrome and may be associated with a catastrophic clinical
      presentation.

PMID- 16569366
TI  - Cognitive dysfunction in the patient with antiphospholipid antibodies:
      considerations for cause and treatment.
AB  - The evidence supporting a causal relationship between antiphospholipid (aPL)
      antibodies and cognitive dysfunction is very limited despite a general impression
      that one exists. Patients with aPL antibodies may complain of cognitive
      difficulties in their everyday lives, forcing the clinician to examine this
      issue. As with other non-thrombotic antiphospholipid syndrome (APS)
      manifestations, cognitive dysfunction in this population should be approached as
      a diagnosis of exclusion. The complexity in diagnosing and treating various
      manifestations of rheumatic disease holds true for identifying and addressing
      cognitive decline in these patients.

PMID- 16569368
TI  - The prevalence and clinical significance of antiphospholipid antibodies in
      rheumatoid arthritis.
AB  - Published data were reviewed to evaluate the occurrence of antiphospholipid
      antibodies (aPL) in rheumatoid arthritis (RA) patients and to investigate their
      clinical relevance in this population. The mean prevalence was calculated at 28%
      and the median was 22%. Few studies have found a relationship between aPL
      antibodies and thrombosis, particularly in combination with other risk factors.
      Conflicting results have been reported on the association of anticardiolipin
      (aCL) antibody positivity and neurologic symptoms, Reynaud's phenomenon, disease
      activity, radiographic erosions, extra-articular RA manifestations, rheumatoid
      factor, and atherosclerosis. Some studies, however, suggest that there is a
      correlation present between those antibodies and C-reactive protein levels,
      rheumatoid nodules, and antinuclear antibodies. TNF-alpha blocking agents may
      cause an induction of aCL antibodies, but it seems like they do not cause any
      clinical features related to the antiphospholipid syndrome. Higher 17beta
      estradiol levels were observed in aCL antibody-positive RA patients than in aCL
      antibody-negative patients and especially in premenopausal women, which may
      predispose to a more efficient immune response.

PMID- 16569369
TI  - Do antiphospholipid antibodies develop for a purpose?
AB  - There is a growing body of literature suggesting that antiphospholipid antibodies
      develop for a purpose, that they play several key roles in the innate immune
      response, and are only rendered pathologic in susceptible people under adverse
      intravascular conditions. This paper will review evidence that the autoantibodies
      associated with the antiphospholipid syndrome develop from natural autoantibodies
      for purposes that are beneficial to host defense, and are only rendered
      pathologic as a result of adverse intravascular events.

PMID- 16569370
TI  - Management of the antiphospholipid syndrome.
AB  - Antiphospholipid antibodies are associated with a hypercoagulable state leading
      to a wide variety of systemic manifestations and obstetric complications. The
      different pathologic manifestations can be a result of arterial and venous
      thrombosis, microthrombotic angiopathy, embolization, obstetric disease, and non
      thrombotic phenomenon. Presently, the treatment centers on anticoagulation. Two
      randomized prospective studies in patients with antiphospholipid syndrome with
      initial thromboembolic event support the target international normalized ratio of
      2.0 to 3.0 for the prevention of future thrombotic events. With pregnancy, the
      combination of aspirin and heparin is still the standard of care. In addition,
      non-thrombotic features and any associated autoimmune disease may need to be
      treated. Underlying risk factors precipitating the thromboembolic phenomenon need
      to be addressed as well.

PMID- 16569371
TI  - T cells and B cells in the pathogenesis of systemic sclerosis: recent insights
      and therapeutic opportunities.
AB  - Among the earliest pathologic events in systemic sclerosis (SSc) is the
      infiltration of mononuclear cells into the skin lesion. This inflammatory cell
      infiltration precedes the development of fibrosis, suggesting an integral role
      for the presence of these cells in the fibrotic events observed in the lesion.
      However, immunosuppressive therapies that are effective in other autoimmune
      disease have not been successful in the treatment of SSc, making the clinical
      management of this disease very difficult. The aim of this paper is to review the
      latest findings regarding the activation and the functional polarization of T
      cells and their role in the pathogenesis of SSc. Furthermore, the potential role
      of B cells, a hitherto scantily investigated inflammatory cell in SSc, is
      discussed. Understanding the interplay between T and B cells, and the processes
      that promote the fibrotic cytokine pattern seen in these patients is of utmost
      importance for the development of effective therapies to treat the clinical
      complications.

PMID- 16569372
TI  - Microvascular damage in systemic sclerosis: detection and monitoring with
      biomarkers.
AB  - Vascular disease is universal in patients with systemic sclerosis (SSc), but
      there is a wide variability in its severity. It is clear that there is an early
      insult to the microvasculature, followed-up by on-going chronic process. This
      results in profound vascular damage in a subset of patients who develop severe
      events such as digital loss and pulmonary arterial hypertension. Although there
      is abundant evidence of vascular perturbation from studies of peripheral blood in
      SSc, there are few data about the ability to use these biomarkers to predict
      vascular outcomes. This paper examines the possibility of using circulating
      biomarkers to assess vascular disease activity and to predict severe vascular
      events among patients with SSc.

PMID- 16569373
TI  - Transforming growth factor-beta: recent advances on its role in immune tolerance.
AB  - Transforming growth factor-beta (TGF-beta) is a key regulator of immune
      tolerance. In this paper, we will focus on T cells and natural killer (NK) cells,
      which are directly regulated by TGF-beta in vivo. TGF-beta controls T-cell
      activation and differentiation, and is involved in the suppressive function and
      generation of regulatory T cells. Recently, TGF-beta has also been shown to
      directly inhibit NK cell activity. These studies demonstrate that TGF-beta
      utilizes multiple mechanisms to ensure immune tolerance, which is critical in a
      variety of autoimmune and inflammatory disorders. We will also discuss recent
      advances on the role of TGF-beta in immune-mediated diabetes, inflammatory bowel
      disease, arthritis, and systemic lupus erythematosus.

PMID- 16569374
TI  - The role of circulating fibrocytes in fibrosis.
AB  - Fibrocytes are cells that circulate in the peripheral blood and produce
      connective tissue proteins such as vimentin and collagens I and III. Fibrocytes
      are associated with skin lesions, pulmonary fibrosis, and tumors and they
      contribute to the remodeling response by secreting matrix metalloproteinases.
      Fibrocytes can further differentiate, and they are a likely source of the
      contractile myofibroblast that appears in many fibrotic lesions. There is
      evidence in the skin for a prominent role for fibrocytes in the development of
      hypertrophic scars and keloids. In asthma or in experimental models of pulmonary
      fibrosis, fibrocytes have been shown to infiltrate areas of inflammation and
      tissue damage. Fibrocytes constitute part of the stromal response to tumor
      invasion, and there is evidence that these cells may be a prognosticator of
      malignant potential. IL-1, TGF-beta, chemokines, and serum amyloid P modulate the
      appearance and function of fibrocytes. Fibrocytes themselves produce inflammatory
      cytokines, growth factors, and chemokines. The intercellular signals that
      modulate fibrocyte trafficking, proliferation, and differentiation are only
      partially defined, but a better understanding of these signals enable new
      therapies to prevent pathologic fibrosis or to improve the tissue repair
      response.

PMID- 16569375
TI  - Nephrogenic systemic fibrosis: an update.
AB  - Nephrogenic systemic fibrosis (NSF), previously known as nephrogenic fibrosing
      dermopathy, is an emerging systemic fibrosing disorder that develops in the
      setting of renal insufficiency. Since its recognition in 1997, several case
      reports of NSF have been published in the rheumatology literature, reflecting the
      increasing incidence and recognition of this disorder in the United States and
      abroad. As rheumatology professionals are commonly the first to encounter newly
      developing cases, it is imperative that they recognize the symptoms and
      comorbidities of NSF and initiate work-up and treatment. To date, the precise
      causes of NSF have not been established; however, several promising lines of
      inquiry have led to a new model of the disorder. This model speculates that
      circulating fibrocytes of bone marrow origin are aberrantly recruited to the skin
      and other systemic sites by a process likely triggered or exacerbated by
      endothelial damage.

PMID- 16569376
TI  - Ehrlichia infection of the central nervous system.
AB  - Ehrlichiosis in the United States is caused by three closely related bacterial
      species (Ehrlichia chaffeensis, Ehrlichia ewingii, and Anaplasma
      phagocytophilum), all transmitted through tick bite. Although there is variation
      with respect to geography and tick vector, the clinical manifestations are
      similar, and treatment of these infections is identical. Ehrlichiosis can present
      with a spectrum of neurologic manifestations, ranging in severity from headache
      to meningoencephalitis. Treatment is straightforward if the diagnosis is
      suspected, but antibiotic therapy should not be delayed pending laboratory
      confirmation. Doxycycline, the treatment of choice for adults and children with
      suspected ehrlichiosis, has high bioavailability and can be administered orally
      in most cases. Therapy is typically continued at least 3 days after the last
      documented fever. Although there have been no studies specifically evaluating
      duration or dosing of doxycycline for Ehrlichia meningoencephalitis, anecdotal
      reports suggest 100 mg doxycycline administered twice daily is effective, despite
      limited penetration into the cerebrospinal fluid. Because doxycycline interacts
      with CYP3A4 enzymes, there is potential for drug interactions with a number of
      medications. In endemic areas, documentation of coinfection with Borrelia
      burgdorferi, the etiologic agent of Lyme disease, may require prolonging the
      duration of doxycycline therapy.

PMID- 16569377
TI  - Treatment of neurosyphilis.
AB  - In 2001, the incidence of primary and secondary syphilis increased in the United
      States for the first time in a decade. Increasing rates of early syphilis among
      men who have sex with men have been reported in many American cities, with
      similar outbreaks noted in Canada and Europe. In San Francisco, the increase has
      been particularly sharp and accompanied by an increase in the incidence of
      neurosyphilis. Early neurosyphilis develops within weeks to years of primary
      infection and primarily involves the meninges. Syndromes include syphilitic
      meningitis (often accompanied by cranial neuropathies), meningovascular syphilis
      (with associated ischemic stroke), or asymptomatic neurosyphilis. Late
      neurosyphilis occurs years to decades after exposure as cerebral or spinal
      gummatous disease or the classic parenchymal forms affecting the brain (general
      paresis or syphilitic encephalitis) or spinal cord and nerve roots (tabes
      dorsalis). Treponema pallidum, the causative agent, cannot be cultured in vitro,
      and microscopic techniques are laborious. Thus, diagnosis depends on serologic
      tests and cerebrospinal fluid (CSF) examination. The suboptimal sensitivity and
      specificity of these tests complicate diagnosis, particularly among patients
      coinfected with HIV. CSF examination should be performed to evaluate for
      neurosyphilis in all patients with positive serum syphilis serology and
      neurologic, ophthalmic, or tertiary disease, or in those who have failed therapy,
      and in HIV-infected patients with late latent syphilis or syphilis of unknown
      duration. Intravenous penicillin G is the recommended treatment for all forms of
      neurosyphilis and for syphilitic eye disease. An outpatient alternative, if
      adherence can be assured, is intramuscular benzathine penicillin with oral
      probenecid. Newer drugs that penetrate CSF, such as ceftriaxone or azithromycin,
      have not yet been adequately tested for neurosyphilis. Syphilis facilitates
      transmission of HIV (and vice versa), and thus all patients diagnosed with
      syphilis should be offered HIV testing.

PMID- 16569378
TI  - Central nervous system infections in transplantation.
AB  - Central nervous system (CNS) infections are a rare but serious complication of
      transplantation. An appropriate diagnostic workup should be streamlined with
      stratification of infection risk by length and degree of immune suppression,
      lesion localization, and timing. Polymerase chain reaction has high sensitivity
      and specificity for rapid identification of viral infections and should be used
      when available. Early diagnosis is imperative, and biopsy should be pursued if a
      diagnosis is not readily obtained with noninvasive testing. Treatment is pathogen
      specific. Combination antifungal therapy should be considered for cerebral
      aspergillosis. Zygomycetes and related invasive fungi require surgical resection
      and high-dose antifungal therapy. Viral meningoencephalitis therapy should be
      continued until resolution of clinical signs and symptoms, and viral clearance is
      verified with repeat cerebrospinal fluid analysis. Cytomegalovirus encephalitis
      requires ongoing maintenance therapy until clearance of viremia or antigenemia.
      Bacterial meningitis is uncommon in transplantation and should be treated with 21
      days of antibiotics. CNS bacterial abscesses, including nocardiosis, should be
      surgically drained if feasible and treated until resolution of clinical and
      radiographic evidence of infection.

PMID- 16569379
TI  - Amebic meningoencephalitis.
AB  - Amebic meningoencephalitis is an uncommon infection of the central nervous system
      (CNS), the consequences of which are devastating in the vast majority of
      patients. Although it is fortunate that few individuals are affected by the
      infection, with such a low incidence of the disease it has been difficult to
      develop and test treatment approaches that, with the appropriate implementation,
      could be broadly effective. As might be expected, the currently available
      information suggests the possibility that early diagnosis and treatment can
      result in improved survival and possible recovery. It is also possible that some
      ameba families and strains may be less pathogenic than others. In order to
      initiate potentially effective interventions during the early stages, it is
      necessary to be aware of the clinical and epidemiologic features that distinguish
      primary from secondary CNS amebic infection and of the various organisms that are
      associated with these forms of disease. This is not only true for patients with
      the more classical presentations of these infectious syndromes but also for those
      who are "culture negative" for common human CNS pathogens. Such information would
      assist greatly in further delineating the etiopathogenesis and spectrum of
      disease that is associated with amebic infection of the CNS, as well as
      potentially effective therapies.

PMID- 16569381
TI  - Initial treatment of Parkinson's disease.
AB  - Initial treatment of early idiopathic Parkinson's disease (PD) begins with
      diagnosis based on clinical evaluation supplemented by laboratory studies and
      brain imaging to exclude causes of secondary parkinsonism. In most cases, testing
      is normal and the diagnosis of PD rests on clinical criteria. In patients with
      mild symptoms and signs, the diagnosis of PD may not initially be apparent, and
      follow-up evaluation is needed to arrive at a diagnosis. Once the diagnosis is
      made, pharmacologic treatment may not be the first step. First, patient education
      is essential, especially because PD is a high-profile disease for which
      information and misinformation are readily available to patients and families.
      Counseling concerning prognosis, future symptoms, future disability, and
      treatment must be provided. Questions from patients concerning diet, lifestyle,
      and exercise are especially common at this point. The decision of when to
      initiate treatment is the next major consideration. Much controversy but
      relatively little light has been brought to bear on this issue. L-dopa was the
      first major antiparkinson medication to be introduced and remains the "gold
      standard" of treatment. Next in efficacy are the dopamine agonists (DAs). A
      debate has raged concerning whether initial dopaminergic treatment should be with
      L-dopa or DAs. Physicians have been concerned about forestalling the appearance
      of dyskinesias and motor fluctuations, whereas patients have incorrectly
      understood that L-dopa and possibly other antiparkinson drugs have a finite
      duration of usefulness, making it important to defer treatment for as long as
      possible. This has created "L-dopa phobia," which may stand in the way of useful
      treatment. In spite of this controversy, there is uniform agreement that the
      appropriate time to treat is when the patient is beginning to be disabled. This
      varies from patient to patient and depends on age, employment status, nature of
      job, level of physical activity, concern about appearance, and other factors. The
      choice of a specific drug is sometimes dictated by the patient's symptoms. For
      example, L-dopa is preferable for severe akinesia, an anticholinergic may be
      useful when tremor is the most prominent symptom (especially in those aged
      younger than 70 years), and DAs may be indicated for younger patients, more prone
      to dyskinesias and fluctuations, with relatively mild symptoms. It is also
      important to manage non-motor symptoms in patients with early PD. Anxiety and
      depression are particularly common at this stage and may be presenting symptoms
      of PD. Where appropriate, counseling and/or treatment with anxiolytics and
      antidepressants should be considered.

PMID- 16569380
TI  - Current and future treatments in progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is an atypical parkinsonian disorder that,
      in spite of its growing recognition, is still underdiagnosed. For management,
      prognosis, and research, an accurate and early diagnosis is essential. PSP is a
      relentlessly progressive neurodegenerative disorder, clinically characterized by
      parkinsonism with prominent axial involvement and postural instability, bulbar
      symptoms, supranuclear ophthalmoplegia, and executive dysfunction. Abnormal
      neuronal and glial four-repeat tau aggregations affecting the basal ganglia and
      selective brainstem structures result in dysfunction of the five
      frontosubcortical circuits and brainstem functions. Primary therapeutic
      approaches are based on neurotransmitter replacement and palliative strategies.
      This article reviews the experience and challenges with neurotransmitter
      replacement and palliative strategies through an extensive literature search of
      studies published between 1965 and 2005. The role of and limited experience with
      alternative therapies, such as deep brain stimulation and pallidotomy, are also
      discussed. Advances in the development of biological therapies for PSP and a
      better understanding of its etiopathogenesis will likely result from
      epidemiologic studies and developed four-repeat tau-transgenic animal models. The
      management of patients with this disorder poses a considerable challenge and
      includes symptomatic and palliative strategies, as well as education and support,
      to improve the quality of life for patients and their caregivers.

PMID- 16569383
TI  - The diagnosis and treatment of depression in Parkinson's disease.
AB  - Depression is common in Parkinson's disease (PD) and associated with considerable
      morbidity, including a worsening of motor symptoms and measures of quality of
      life. Therefore, patients with PD should be routinely screened for depressive
      symptoms with rating scales such as the Geriatric Depression Scale. Patients
      meeting criteria should be treated using established algorithms for the
      management of depression and associated symptoms such as insomnia, anxiety,
      psychosis, and mania. The algorithm outlined in this paper describes the
      importance of maintaining an adequate dose of medication over a medication trial
      that can last up to 12 weeks. To optimally monitor patients' progress, clinicians
      should also consider using rating scales that measure depression severity, such
      as the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory.

PMID- 16569382
TI  - Huntington's Disease.
AB  - Although available treatments for Huntington's disease (HD) are imperfect,
      thoughtful application can positively impact quality of life. Dopamine
      antagonists can provide control of the troublesome hyperkinetic movements. These
      agents can also diminish the frequency of hallucinations and delusions when
      symptoms of psychosis occur. Classical neuroleptics have the widest utilization,
      although atypical antipsychotics are being increasingly used. Suppression of
      choreiform movements has also been reported with amantadine and tetrabenazine,
      which is not currently approved in the United States but under investigation.
      Alteration in mood can be successfully managed with a variety of antidepressant
      medications. Superior tolerability and value in the management of a variety of
      behavioral disturbances have lead to extensive use of serotonin reuptake
      inhibitors. Modest disturbance of mood can sometimes be addressed with
      anticonvulsant medications. Considered a manifestation of advanced disease,
      dementia is less commonly addressed therapeutically. However, gathering
      experience suggests improved cognitive function can occur with cholinesterase
      inhibitor therapy. Frequently overlooked is the value of rehabilitation services
      in the management of diverse symptoms. Although the value of a dysphagia
      evaluation is apparent, the benefit to be derived from physical and occupational
      therapy involvement cannot be overstated. Current therapeutic trials will
      undoubtedly provide additional therapies to moderate symptoms, but once the
      mechanism(s) of selective striatal projection neuron degeneration are delineated,
      a revolution in the management of HD will occur.

PMID- 16569384
TI  - Essential tremor: treatment options.
AB  - The treatment of essential tremor depends on the tremor severity, location, and
      risk benefit ratios. Mild to moderate tremor usually will respond to oral agents
      such as noncardiac selective beta-blockers or primidone. Other agents including
      ethanol, topiramate, benzodiazepines, gabapentin, levetiracetam, and zonisamide
      may be effective. There are very little data comparing different oral agents, but
      there is support for polypharmacy in some cases. Botulinum toxin injections are
      effective in some tremor patterns, especially wrist flexion/extension and head
      tremor. For severe tremor, surgical lesioning or deep brain stimulation of the
      thalamus is justified and often dramatically improves function.

PMID- 16569387
TI  - Esophageal Cancer Clinical Practice Guidelines.

PMID- 16569388
TI  - Gastric Cancer Clinical Practice Guidelines.

PMID- 16569389
TI  - Barrett's esophagus and its progression to adenocarcinoma.
AB  - Barrett's esophagus (BE) is the only known precursor for esophageal
      adenocarcinoma (EA). Therefore, the presence of BE identifies a high-risk group
      of patients who may be followed-up for early detection of EA and treated to
      reduce the risk for its progression. The initiating event for BE is unknown,
      although it is associated with chronic gastric reflux. Many of the genetic
      lesions involved in BE neoplastic progression are known, including loss of CDKN2A
      (p16) and TP53 (p53) and the development of tetraploidy and aneuploidy. Intensive
      endoscopic surveillance has been shown to improve survival although it can be
      difficult to implement in practice. Several exposures may be altered to reduce
      the risk for progression, including weight, diet, and the use of nonsteroidal
      anti-inflammatory drugs. However, most of these results should be confirmed in
      additional cohorts before they are used to change clinical practice.

PMID- 16569390
TI  - Combined modality therapy of localized gastric and esophageal cancers.
AB  - Gastric and esophageal cancers continue to be a significant health problem. The
      incidence of proximal gastric and distal esophageal cancers has been increasing,
      especially in white men. Gastric and esophageal cancers have high rates of
      locoregional and distant failure, resulting in poor overall survival. Therefore,
      patients with gastric and esophageal cancer may benefit from combined modality
      therapy. Adjuvant chemoradiation has been shown to improve survival in gastric
      and gastroesophageal cancers in a phase III trial. In esophageal cancer, most
      randomized trials have not shown a survival benefit for preoperative chemotherapy
      or chemoradiation, although these approaches are widely used. This article
      reviews the role of staging, surgery, and adjuvant and preoperative therapies in
      the management of localized gastric and esophageal cancers.

PMID- 16569391
TI  - Colorectal Cancer Screening Clinical Practice Guidelines.

PMID- 16569392
TI  - Current approaches in familial colorectal cancer: a clinical perspective.
AB  - Individuals with a family history of colorectal cancer or colorectal adenomas
      have an increased risk for colorectal cancer. When no hereditary syndrome is
      evident, screening is based on empiric risk estimates. The risk is greatest for
      individuals with specific inherited cancer-predisposing disorders. When
      conditions such as familial adenomatous polyposis or hereditary nonpolyposis
      colorectal cancer are diagnosed, specific neoplasm risk estimates can usually be
      performed based on advances in molecular genetics. These estimates lead to more
      straightforward and cost-effective approaches to surveillance and management. The
      National Comprehensive Cancer Center Network (NCCN) and other groups have
      provided detailed guidelines for evaluating patients based on recognition of
      clinical syndrome characteristics, followed by appropriate genetic counseling,
      genetic testing, and optimal surveillance. The NCCN guidelines are used as a
      frame of reference for this discussion of selected recent advances in human
      cancer genetics as they apply to clinical practice.

PMID- 16569393
TI  - Microradiographic study on the effects of mucin-based solutions used as saliva
      substitutes on demineralised bovine enamel in vitro.
AB  - Sialic acids and proteins bound to mucins are known to form complexes with
      calcium, and this mechanism may hamper the remineralization of calcium-containing
      mucin-based saliva substitutes. Thus, the aim of this investigation was to
      evaluate the effects of adding various concentrations of calcium phosphate to
      self-made mucin-containing solutions on demineralised bovine enamel in vitro.
      Bovine specimens were prepared, embedded in epoxy resin, and polished to 4000
      grit. Subsequently, the surfaces of the specimens were partially covered with
      nail varnish, thus serving as a control of sound enamel, and demineralised (37
      degrees C; pH 5.0) for 14 (19 groups; n=10) or 28 days (three groups; n=9). After
      demineralization, the specimens were exposed to mucin-based solutions (30 g/l)
      with various saturations with respect to apatites containing 0.1 mM NaF, CaCl(2)
      (0-20 mM) and KH(2)PO(4) (0-52 mM) at two different pH values (5.5 or 6.5). A
      fluoride-free solution and the commercially available saliva substitute Saliva
      Orthana (Orthana, Kastrup, Copenhagen Denmark) served as controls. The
      differences in mineral loss (DeltaDeltaZ) between the values prior to
      (DeltaZ(Demin)) and after storage (DeltaZ(Effect)) in the various solutions were
      evaluated from microradiographs of thin sections (100 microm). The general linear
      model revealed a significant dependency of DeltaDeltaZ for calcium (P=0.006), but
      not for phosphate (P=0.081) or pH (P=0.114). DeltaZ(Effect) was only
      significantly reduced compared with DeltaZ(Demin) in the group with the highest
      saturation with respect to hydroxyapatite (P<0.05; t-test). In conclusion, mucin
      based saliva substitutes with an adequate composition are able to remineralize
      bovine enamel in vitro.

PMID- 16569395
TI  - The chlorophyll a fluorescence induction pattern in chloroplasts upon repetitive
      single turnover excitations: accumulation and function of QB-nonreducing centers.
AB  - The increase of chlorophyll fluorescence yield in chloroplasts in a 12.5 Hz train
      of saturating single turnover flashes and the kinetics of fluorescence yield
      decay after the last flash have been analyzed. The approximate twofold increase
      in Fm relative to Fo, reached after 30-40 flashes, is associated with a
      proportional change in the slow (1-20 s) component of the multiphasic decay. This
      component reflects the accumulation of a sizeable fraction of QB-nonreducing
      centers. It is hypothesized that the generation of these centers occurs in
      association with proton transport across the thylakoid membrane. The data are
      quantitatively consistent with a model in which the fluorescence quenching of QB
      nonreducing centers is reversibly released after second excitation and electron
      trapping on the acceptor side of Photosystem II.

PMID- 16569396
TI  - Effects of suppression, acceptance and spontaneous coping on pain tolerance, pain
      intensity and distress.
AB  - Wegner's Theory of Ironic Processes has been applied to study the effects of
      cognitive strategies to control pain. Research suggests that suppression
      contributes to a more distressing pain experience. Recently, the acceptance-based
      approach has been proposed as an alternative to cognitive control. This study
      assessed the tolerance time, the distress and the perceived pain intensity in
      three groups (suppression, acceptance and spontaneous coping groups) when the
      participants were exposed to a cold pressor procedure. Two hundred and nineteen
      undergraduates volunteered to participate. The suppression group showed the
      shortest tolerance time and the acceptance group showed the longest tolerance
      time. The acceptance group showed pain and distress immersion ratings that were
      significantly lower than in the other two groups, between which the differences
      were not significant. In the first recovery period, the suppression group showed
      pain and distress ratings that were higher than in the other two groups. In the
      second recovery period, although the acceptance group showed pain and distress
      ratings that were significantly lower than in the other two groups, the
      suppression and the spontaneous coping groups did not differ. The presence of a
      'rebound' of physical discomfort and the effects of suppression on behavioural
      avoidance are discussed. These results support the acceptance approach in the
      management of pain.

PMID- 16569397
TI  - Distribution of tocopheryl quinone in mitochondrial membranes and interference
      with ubiquinone-mediated electron transfer.
AB  - Alpha-tocopherol (Toc) is an efficient lipophilic antioxidant present in all
      mammalian lipid membranes. This chromanol is metabolized by two different
      pathways: excessive dietary Toc is degraded in the liver by side chain oxidation,
      and Toc acting as antioxidant is partially degraded to alpha-tocopheryl quinone
      (TQ). The latter process and the similarity between TQ and ubiquinone (UQ)
      prompted us to study the distribution of TQ in rat liver mitochondrial membranes
      and the interference of TQ with the activity of mitochondrial and microsomal
      redox enzymes interacting with UQ. In view of the contradictory literature
      results regarding Toc, we determined the distribution of Toc, TQ, and UQ over
      inner and outer membranes of rat liver mitochondria. Irrespective of the
      preparation method, the TQ/Toc ratio tends to be higher in mitochondrial inner
      membranes than in outer membranes suggesting TQ formation by respiratory
      oxidative stress in vivo. The comparison of the catalytic activities using short
      chain homologues of TQ and UQ showed decreasing selectivity in the order complex
      II (TQ activity not detected)>Q(o) site of complex III>Q(i) site of complex
      III>complex I approximately cytochrome b(5) reductase>cytochrome P-450 reductase
      (comparable reactivity of UQ and TQ). TQ binding to some enzymes is comparable to
      UQ despite low activities. These data show that TQ arising from excessive
      oxidative degradation of Toc can potentially interfere with mitochondrial
      electron transfer. On the other hand, both microsomal and mitochondrial enzymes
      contribute to the reduction of TQ to tocopheryl hydroquinone, which has been
      suggested to play an antioxidative role itself.

PMID- 16569399
TI  - The adult mouse utricle as an in vitro preparation for studies of ototoxic-drug
      induced sensory hair cell death.
AB  - Sensory hair cells of the inner ear are susceptible to death from a variety of
      stresses including aging, noise trauma, genetic disorders, and exposure to
      certain therapeutic drugs. Ototoxic drugs include the aminoglycoside antibiotics
      and the antineoplastic agent cisplatin. This is a short technical report
      describing the dissection and culture of the adult mouse utricle. This in vitro
      preparation allows for detailed studies of ototoxic-drug-induced hair cell death
      in an adult mammalian system. In addition, this preparation allows for
      examination of the effects of specific gene products through the use of
      transgenic and knockout mouse models.

PMID- 16569400
TI  - Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture by
      a survival pathway targeting SR Ca2+ storage.
AB  - OBJECTIVE: Experimental and clinical studies have shown that administration of
      insulin during reperfusion is cardioprotective, but the underlying mechanisms are
      still unknown. In this study, we investigated in isolated rat cardiomyocytes
      subjected to hypoxia and reoxygenation whether administration of insulin during
      reoxygenation reduces reoxygenation-induced hypercontracture, a hallmark of acute
      reperfusion injury. The effects of insulin on potential pro-survival kinases,
      i.e., PI 3-kinase, NO synthase (eNOS), and cGMP-dependent protein kinase (PKG),
      and on cytosolic Ca2+ control in reoxygenated cardiomyocytes were investigated.
      RESULTS: Administration of insulin (10 mU/L) during reoxygenation protected
      cardiomyocytes against hypercontracture development (cell length as % of end
      hypoxic length: control 61.6+/-3.2; insulin 76.3+/-2.9; n=26; p<0.05 vs.
      control). Cytosolic [Ca2+] recovery during the first 2 min of reoxygenation was
      accelerated (fura-2 ratio after 2 min of reoxygenation; control 1.01+/-0.05;
      insulin 0.79+/-0.04; n=26; p<0.05 vs. control). The beneficial effects of insulin
      on cytosolic [Ca2+] recovery and hypercontracture were suppressed in the presence
      of inhibitors of PI 3-kinase (LY294002, 1 microM), eNOS (L-NMMA, 100 microM), PKG
      (KT 5823, 1 microM), or sarcoplasmic reticulum Ca2+ pump (SERCA) (thapsigargin,
      150 nM). Insulin increased phosphorylation and activity of eNOS and augmented
      phospholamban phosphorylation in reoxygenated cardiomyocytes. Correlated with
      phospholamban phosphorylation, insulin also augmented SR Ca2+ load. CONCLUSIONS:
      Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture.
      This is due to acceleration of cytosolic [Ca2+] recovery by enhanced Ca2+
      sequestration into the sarcoplasmic reticulum via SERCA activation. This
      protective mechanism is activated through the survival pathway consisting of PI 3
      kinase, eNOS, and PKG.

PMID- 16569398
TI  - Long term environmental tobacco smoke activates nuclear transcription factor
      kappa B, activator protein-1, and stress responsive kinases in mouse brain.
AB  - Environmental tobacco smoke (ETS) is a key mediator of several diseases. Tobacco
      smoke contains a mixture of over 4700 chemical components many of which are toxic
      and have been implicated in the etiology of oxidative stress related diseases
      such as chronic obstructive pulmonary disease, Parkinson's disease, asthma,
      cancer and cardiovascular disease. However, the mechanism of action of cigarette
      smoke in the onset of these diseases is still largely unknown. Previous studies
      have revealed that the free radicals generated by cigarette smoke may contribute
      to many of these chronic health problems and this study sought to address the
      role of environmental tobacco smoke in oxidative stress related damage in
      different regions of the mouse brain. In this study, male mice were exposed for
      7h/day, 7 days/week, for 6 months. Our results show that tobacco smoke led to
      increased generation of reactive oxygen species with an increase in NF-kappaB
      activation. Gel shift analysis also revealed the elevated level of the oxidative
      stress sensitive proinflammatory nuclear transcription factor-kappa B and
      activator protein-1 in different regions of the brain of cigarette smoke exposed
      mice. Tobacco smoke led to activation of COX-2 in all the regions of the brain.
      Activation of mitogen activated protein kinase and c-Jun N-terminal kinase were
      also observed in various regions of brain of ETS exposed mice. Overall our
      results indicate that exposure to long-term cigarette smoke induces oxidative
      stress leading to activation of stress induced kinases and activation of
      proinflammatory transcription factors.

PMID- 16569401
TI  - The role of lipid-protein interactions in amyloid-type protein fibril formation.
AB  - Structural transition of polypeptide chains into the beta-sheet state followed by
      amyloid fibril formation is the key characteristic of a number of the so-called
      conformational diseases. The multistep process of protein fibrillization can be
      modulated by a variety of factors, in particular by lipid-protein interactions. A
      wealth of experimental evidence provides support to the notion that amyloid
      fibril assembly and the toxicity of pre-fibrillar aggregates are closely related
      and are both intimately membrane associated phenomena. The present review
      summarizes the principal factors responsible for the enhancement of fibril
      formation in a membrane environment, viz. (i) structural transformation of
      polypeptide chain into a partially folded conformation, (ii) increase of the
      local concentration of a protein upon its membrane binding, (iii) aggregation
      favoring orientation of the bound protein, and (iv) variation in the depth of
      bilayer penetration affecting the nucleation propensity of the membrane
      associated protein. The molecular mechanisms of membrane-mediated protein
      fibrillization are discussed. Importantly, the toxicity of lipid-induced pre
      fibrillar aggregates is likely to have presented a very strong negative selection
      pressure in the evolution of amino acid sequences.

PMID- 16569402
TI  - Combining precision spin-probe partitioning with time-resolved fluorescence
      quenching to study micelles. Application to micelles of pure
      lysomyristoylphosphatidylcholine (LMPC) and LMPC mixed with sodium dodecyl
      sulfate.
AB  - Micelles of lysomyristoylphosphatidylcholine (LMPC) and mixed micelles of LMPC
      with anionic detergent sodium dodecyl sulfate (SDS) have been characterized by
      spin-probe-partitioning electron paramagnetic resonance (SPPEPR) and time
      resolved fluorescence quenching (TRFQ) experiments. SPPEPR is a novel new method
      to study structure and dynamics in lipid assemblies successfully applied here for
      the first time to micelles. Several improvements to the computer program used to
      analyze SPPEPR spectra have been incorporated that increase the precision in the
      extracted parameters considerably from which micelle properties such as effective
      water concentration and microviscosity may be estimated. In addition, with this
      increased precision, it is shown that it is feasible to study the rate of
      transfer of a small spin probe between micelles and the surrounding aqueous phase
      by SPPEPR. The rate of transfer of the spin probe di-tert-butyl nitroxide (DTBN)
      and the activation energy of the transfer process in LMPC and LMPC-SDS micelles
      have been determined with high precision. The rate of transfer increases with
      temperature and SDS molar fraction in mixed micelles, while it remains constant
      with LMPC concentration in pure LMPC micelles. The activation energy of DTBN
      transfer in pure lysophospholipid micelles does not change with LMPC
      concentration while it decreases with the increasing molar fraction of SDS in
      mixed LMPC-SDS micelles. Both this decrease in activation energy and the increase
      in the rate of transfer are rationalized in terms of an increasing micelle
      surface area per molecule (decreasing compactness) as SDS molecules are added.
      This decreasing compactness as a function of SDS content is confirmed by TRFQ
      measurements showing an aggregation number that decreases from 122 molecules for
      pure LMPC micelles to 80 molecules for pure SDS micelles. The same increase in
      surface area per molecule is predicted to increase the effective water
      concentration in the polar shell of the micelles. This increase in hydration with
      SDS molar fraction is confirmed by measuring the effective water concentration in
      the polar shell of the micelles from the hyperfine spacing of DTBN. This work
      demonstrates the potential to design mixed lysophospholipid surfactant micelles
      with variable physicochemical properties. Well-defined micellar substrates, in
      terms of their physicochemical properties, may improve the studies of protein
      structure and enzyme kinetics.

PMID- 16569403
TI  - Frequency of the deletion polymorphism of DNASE1L1 in 137 patients with acid
      maltase deficiency (Pompe disease).

PMID- 16569404
TI  - When things do not go right.

PMID- 16569405
TI  - The incidence and severity of injury in children hospitalised for traumatic brain
      injury in Kashmir.
AB  - A large number of people experience traumatic brain injury each year, often with
      severe consequences. This is a public health problem that requires ongoing
      surveillance to follow trends in the incidence, risk factors, causes, and
      outcomes of these injuries. In 2003, a prospective study of all children below 15
      years admitted to hospitals with a diagnosis of head injury was conducted in the
      Accident & Emergency Department of Sher-e-Kashmir Institute of Medical Sciences,
      Srinagar (India) to determine the incidence and severity of accidental head
      injury among children and the circumstances of injury. The highest incidence of
      head injury was seen at ages 6-10 years. Head injury rates were higher in males
      than in females. The leading causes include falls and motor vehicle accidents.
      More than 50% falls occurred in the age group of 4-6 years. Ninety per cent
      patients, who recovered, were discharged within 16-24 h after admission. Lack of
      supervision, non-implementation of safety measures and poor implementation of
      traffic rules leads to many injuries. The ability of the health care system to
      deal with increasing trauma in Jammu & Kashmir is limited. Nevertheless,
      prevention can be low cost strategy to overcome this problem. The results of
      epidemiological studies are affected by factors like demography, geographic
      region and socioeconomic status. This study emphasizes the need for intensified
      effort for prevention, minimising risk factors, strict legislative measures,
      observing traffic rules, implementation of safety measures, establishing
      appropriate trauma care at district level, adult supervision, and creating
      awareness.

PMID- 16569406
TI  - Family witness resuscitation. Allow or deny? Which is true?

PMID- 16569407
TI  - Awareness of blood pressure among older adults: a cross-sectional descriptive
      study.
AB  - OBJECTIVES: To measure the degree that elderly persons are knowledgeable about
      blood pressure (BP) and hypertension in general and are aware of their own BP in
      particular and to determine the degree that such knowledge and awareness relates
      to actual BP readings. DESIGN AND SETTING: A cross-sectional descriptive study
      was conducted at the senior activity centers. METHODS: A convenience sample of
      276 men and women between 60 and 75 years completed two BP measurements,
      cognitive impairment assessments, a 21-item Awareness of Blood Pressure
      Questionnaire, motivation for health, and personal information. FINDINGS:
      Individuals indicated much less awareness about their own BP than their self
      reported behaviors about their BP would suggest. Of the participants, 74% were
      aware of their BP, while 90% reported asking about their BP on visits to
      healthcare providers; 32% of those with isolated systolic hypertension were
      unaware of their hypertensive status. More than half of the participants had
      inaccurate knowledge about BP in general and about systolic BP as it related to
      the aging process. Knowledge of BP and hypertension was higher among people who
      knew their own BP levels. CONCLUSIONS: The study revealed that one's awareness of
      BP does not necessarily reflect one's actual BP status. This finding deserves the
      attention of older adults and healthcare providers who consider patient awareness
      as fundamental to behavioral change and BP control.

PMID- 16569408
TI  - Cytokine profiles and T cell function in acute coronary syndromes.
AB  - AIMS: In advanced human atherosclerotic plaques infiltrating T cells congregate
      at sites of plaque rupture. However, little is known about the systemic
      activation of circulating T cells in acute coronary syndromes as a prerequisite
      for recruitment to atherosclerotic lesions. METHODS AND RESULTS: As a measure for
      specific lymphocyte activation we analyzed IFN-gamma production of T cells after
      stimulation with a superantigen and expression of CXCR-3 and CCR-3 in patients
      with acute myocardial infarction (AMI), unstable angina (uAP) or stable angina
      (sAP). Furthermore, concentrations of the circulating cytokines interleukin (IL)
      1, IL-6, IL-1beta, IL-12 p70 and RANTES that modify T cell function were
      measured. In uAP an increased Th1 and a decreased Th2 response was identified by
      enhanced interferon-gamma generation of T lymphocytes, increased levels of IL
      1beta, IL-12 p70 and RANTES and decreased expression of CCR3. In AMI a systemic
      inflammatory reaction predominates with enhanced expression of the early
      activation marker CD69 on T lymphocytes and elevated levels of IL-6 and IL-10
      that suppress Th1 activation. CONCLUSION: Interferon-gamma production of
      activated T cells in acute coronary syndromes may, therefore, be governed by the
      release of specific pro- and anti-lymphocyte activating cytokines.

PMID- 16569409
TI  - Correlates of vascular structure and function measures in asymptomatic young
      adults: the Bogalusa Heart Study.
AB  - BACKGROUND: Adverse changes in arterial structure and function, independent
      predictors of cardiovascular (CV) disease morbidity and mortality, are known to
      be associated with CV risk factors, especially in middle-aged and older adults.
      Although non-invasive studies in this regard are beginning to emerge in a younger
      age population, information is lacking on the correlates of measures of vascular
      structure and function obtained simultaneously by different non-invasive methods.
      METHODS: In 518 black and white subjects (72% white, 44% male) aged 27-43 years,
      vascular structure and function were measured in terms of (1) carotid artery
      intima-media thickness (IMT), (2) aorta-femoral pulse wave velocity (af-PWV), and
      (3) pulsatile arterial function in terms of large (C1) and small (C2) artery
      compliances. RESULTS: Blacks versus whites and males versus females had higher
      carotid IMT; blacks versus whites higher af-PWV; and blacks versus whites and
      females versus males lower C1 and C2. In a multivariate regression model,
      significant predictors in the order of entry into the model were systolic blood
      pressure, male gender, age, cigarette smoking, and LDL cholesterol for carotid
      IMT (R(2)=0.189); systolic blood pressure, homeostasis model assessment of
      insulin resistance (HOMA-IR), cigarette smoking, and age for af-PWV (R(2)=0.200);
      systolic blood pressure, female gender, and HOMA-IR for C1 (R(2)=0.258); and
      systolic blood pressure, female gender, age, diastolic blood pressure, cigarette
      smoking, triglycerides, and black race for C2 (R(2)=0.394). CONCLUSION: In
      asymptomatic young adults, CV risk factors influence adversely measures of both
      structure and function of the vasculature to varying degrees, with small artery
      compliance showing maximum variance. As part of preventive cardiology, assessment
      of structure/function measures of the vasculature by simple non-invasive methods
      may be helpful in identifying early vascular damage in a high-risk young
      population group.

PMID- 16569411
TI  - Determination of solute partition behavior with room-temperature ionic liquid
      based micellar gas-liquid chromatography stationary phases using the pseudophase
      model.
AB  - The use of micelles in ionic liquid based gas-chromatography stationary phases
      was evaluated using equations derived for a "three-phase" model. This model
      allows the determination of all three partition coefficients involved in the
      system, and elucidates the micellar contribution to retention and selectivity.
      Four types of micellar-ionic liquid columns were examined in this study: 1-butyl
      3-methylimidazolium chloride with sodium dodecylsulfate or dioctyl
      sulfosuccinate, and 1-butyl-3-methylimidazolium hexafluorophosphate with
      polyoxyethylene-100-stearyl ether or polyoxyethylene-23-lauryl ether. The
      partition coefficients were measured for a wide range of probe molecules capable
      of a variety of types and magnitudes of interactions. In general, most probe
      molecules preferentially partitioned to the micellar pseudophase over the bulk
      ionic liquid component of the stationary phase. Therefore, addition of surfactant
      to the stationary phase usually resulted in greater solute retention. It is also
      shown that the selectivity of the stationary phase is significantly altered by
      the presence of micelles, either by enhancing or lessening the separation. The
      effects of surfactant on the interaction parameters of the stationary phase are
      determined using the Abraham solvation parameter model. The addition of sodium
      dodecylsulfate and dioctyl sulfosuccinate to 1-butyl-3-methylimidazolium chloride
      stationary phases generally increased the phase's hydrogen bond basicity and
      increased the level of dispersion interaction. Polyoxyethylene-100-stearyl ether
      and polyoxyethylene-23-lauryl ether surfactants, however, enhanced the pi-pi/n
      pi, polarizability/dipolarity, and hydrogen bond basicity interactions of 1-butyl
      3-methylimidazolium hexafluorophosphate to a greater degree than the ionic
      surfactants with 1-butyl-3-methylimidazolium chloride. However, these nonionic
      surfactants appeared to hinder the ability of the stationary phase to interact
      with solutes via dispersion forces. Therefore, it is possible to effectively
      predict which analytes will be most highly retained by these micellar-ionic
      liquid stationary phases.

PMID- 16569410
TI  - Application of a single-drop microextraction for the analysis of organophosphorus
      pesticides in juice.
AB  - In this study, a new method for the determination of organophosphorus pesticides
      (OPPs) (ethoprophos, diazinon, parathion methyl, fenitrothion, malathion,
      isocarbophos and quinaphos) in orange juice was developed. Single-drop
      microextraction (SDME) parameters, such as organic solvent, drop volume,
      agitation rate, extraction time, and salt concentration were optimized through
      analysis of OPPs in fortified water. The orange juice was simply centrifuged and
      diluted with water, extracted by SDME and analyzed by gas chromatography (GC)
      equipped with a flame photometric detection (FPD). Fortification tests were
      conducted for concentrations between 10 and 500 microg/L; mean relative
      recoveries for each pesticide were all above 76.2% and below 108.0%. Limits of
      detection of the method for orange juice were below 5 microg/L for all target
      pesticides. The repeatability of the proposed method, expressed as relative
      standard deviation varied between 4.6 and 14.1% (n=5). The proposed method is
      acceptable in the analysis of OPPs pesticides in juice matrices.

PMID- 16569412
TI  - A principal calling: professionalism and health care services.
AB  - As heath care professionals, our "product" is clinical service. We demonstrate
      professionalism by attitudes, knowledge, and behaviors that reflect a multi
      faceted approach to the standards, regulations, and principles underlying
      successful clinical practices. The issues facing practitioners who work in health
      care environments are complex, forming an infrastructure for conducting clinical
      and business operations. Issues discussed include: clinical quality and outcomes
      management; patient safety and medical errors; accreditation and compliance. A
      thorough knowledge of these topics forms the context within which we integrate
      our services with the larger health care community. In this age of
      accountability, inquiry, introspection and integrity are the keys to
      professionalism. LEARNING OUTCOMES: As a result of this activity, the reader will
      be able to: (1) discuss basic points related to the complex requirements and
      issues facing clinical practitioners today; (2) understand the components of
      "professional" practice within the health care community; (3) integrate quality
      management, regulatory compliance, and accreditation standards into every
      clinical practice. Profession: A calling requiring specialized knowledge and
      often long and intensive academic preparation; a principal calling, vocation, or
      employment. Professionalism: The conduct, aims, or qualities that characterize or
      mark a profession or professional person. -Webster's New Collegiate Dictionary.

PMID- 16569413
TI  - Robust translocation along a molecular monorail: the NS3 helicase from hepatitis
      C virus traverses unusually large disruptions in its track.
AB  - The NS3 helicase is essential for replication of the hepatitis C virus. This
      multifunctional Superfamily 2 helicase protein unwinds nucleic acid duplexes in a
      stepwise, ATP-dependent manner. Although kinetic features of its mechanism are
      beginning to emerge, little is known about the physical determinants for NS3
      translocation along a strand of nucleic acid. For example, it is not known
      whether NS3 can traverse covalent or physical discontinuities on the tracking
      strand. Here we provide evidence that NS3 translocates with a mechanism that is
      different from its well-studied relative, the Vaccinia helicase NPH-II. Like NPH
      II, NS3 translocates along the loading strand (the strand bearing the 3'
      overhang) and it fails to unwind substrates that contain nicks, or covalent
      discontinuities in the loading strand. However, unlike NPH-II, NS3 readily
      unwinds RNA duplexes that contain long stretches of polyglycol, which are
      moieties that bear no resemblance to nucleic acid. Whether located on the
      tracking strand, the top strand, or both, long polyglycol regions fail to disrupt
      the function of NS3. This suggests that NS3 does not require the continuous
      formation of specific contacts with the ribose-phosphate backbone as it
      translocates along an RNA duplex, which is an observation consistent with the
      large NS3 kinetic step size (18 base-pairs). Rather, once NS3 loads onto a
      substrate, the helicase can translocate along the loading strand of an RNA duplex
      like a monorail train following a track. Bumps in the track do not significantly
      disturb NS3 unwinding, but a break in the track de-rails the helicase.

PMID- 16569414
TI  - I-BasI and I-HmuI: two phage intron-encoded endonucleases with homologous DNA
      recognition sequences but distinct DNA specificities.
AB  - I-HmuI and I-BasI are two highly similar nicking DNA endonucleases, which are
      each encoded by a group I intron inserted into homologous sites within the DNA
      polymerase genes of Bacillus phages SPO1 and Bastille, respectively. Here, we
      present a comparison of the DNA specificities and cleavage activities of these
      enconucleases with homologous target sites. I-BasI has properties that are
      typical of homing endonucleases, nicking the intron-minus polymerase genes in
      either host genome, three nucleotides downstream of the intron insertion site. In
      contrast, I-HmuI nicks both the intron-plus and intron-minus site in its own host
      genome, but does not act on the target from Bastille phage. Although the enzymes
      have distinct DNA substrate specificities, both bind to an identical 25bp region
      of their respective intron-minus DNA polymerase genes surrounding the intron
      insertion site. The endonucleases appear to interact with the DNA substrates in
      the downstream exon 2 in a similar manner. However, whereas I-HmuI is known to
      make its only base-specific contacts within this exon region, structural modeling
      analyses predict that I-BasI might make specific base contacts both upstream and
      downstream of the site of intron insertion. The predicted requirement for base
      specific contacts in exon 1 for cleavage by I-BasI was confirmed experimentally.
      This explains the difference in substrate specificities between the two enzymes,
      including the observation that the former enzyme is relatively insensitive to the
      presence of an intron upstream of exon 2. These differences are likely a
      consequence of divergent evolutionary constraints.

PMID- 16569415
TI  - Mechanism of drug resistance revealed by the crystal structure of the unliganded
      HIV-1 protease with F53L mutation.
AB  - Mutations in HIV-1 protease (PR) that produce resistance to antiviral PR
      inhibitors are a major problem in AIDS therapy. The mutation F53L arising from
      antiretroviral therapy was introduced into the flexible flap region of the wild
      type PR to study its effect and potential role in developing drug resistance.
      Compared to wild-type PR, PR(F53L) showed lower (15%) catalytic efficiency, 20
      fold weaker inhibition by the clinical drug indinavir, and reduced dimer
      stability, while the inhibition constants of two peptide analog inhibitors were
      slightly lower than those for PR. The crystal structure of PR(F53L) was
      determined in the unliganded form at 1.35 Angstrom resolution in space group
      P4(1)2(1)2. The tips of the flaps in PR(F53L) had a wider separation than in
      unliganded wild-type PR, probably due to the absence of hydrophobic interactions
      of the side-chains of Phe53 and Ile50'. The changes in interactions between the
      flaps agreed with the reduced stability of PR(F53L) relative to wild-type PR. The
      altered flap interactions in the unliganded form of PR(F53L) suggest a distinct
      mechanism for drug resistance, which has not been observed in other common drug
      resistant mutants.

PMID- 16569416
TI  - Alternate structural conformations of Streptococcus pneumoniae hyaluronan lyase:
      insights into enzyme flexibility and underlying molecular mechanism of action.
AB  - Streptococcus pneumoniae hyaluronan lyase is a surface enzyme of this Gram
      positive bacterium. The enzyme degrades several biologically important,
      information-rich linear polymeric glycans: hyaluronan, unsulfated chondroitin,
      and some chondroitin sulfates. This degradation facilitates spreading of bacteria
      throughout the host tissues and presumably provides energy and a carbon source
      for pneumococcal cells. Its beta-elimination catalytic mechanism is an acid/base
      process termed proton acceptance and donation leading to cleavage of beta-1,4
      linkages of the substrates. The degradation of hyaluronan occurs in two stages,
      initial endolytic cuts are followed by processive exolytic cleavage of one
      disaccharide at a time. In contrast, the degradation of chondroitins is purely
      endolytic. Structural studies together with flexibility analyses of two
      streptococcal enzymes, from S.pneumoniae and Streptococcus agalactiae, allowed
      for insights into this enzyme's molecular mechanism. Here, two new X-ray crystal
      structures of the pneumococcal enzyme in novel conformations are reported. These
      new conformations, complemented by molecular dynamics simulation results,
      directly confirm the predicted domain motions presumed to facilitate the
      processive degradative process. One of these new structures resembles the
      S.agalactiae enzyme conformation, and provides evidence of a uniform
      mechanistic/dynamic behavior of this protein across different bacteria.

PMID- 16569417
TI  - Automated, fast and sensitive quantification of 17 alpha-hydroxy-progesterone,
      androstenedione and testosterone by tandem mass spectrometry with on-line
      extraction.
AB  - Plasma 17 alpha-hydroxyprogesterone (17-OHP), androstenedione and testosterone
      measurements are important for the diagnosis and monitoring of hyperandrogenic
      disorders, most importantly for congenital adrenal hyperplasia (CAH) due to 21
      hydroxylase deficiency. The reliability of immunoassays has proved questionable
      especially for newborns and children. In order to reduce the analytical
      interferences due to cross-reactivity or matrix effects, to improve accuracy and
      shorten the analysis time, we have developed a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method with atmospheric pressure chemical ionization
      (APCI) for simultaneous measurement. An on-line extraction cartridge with column
      switching technique and liquid chromatography over a Chromolith RP 18 e column
      allow a rapid and easy quantification. The lowest limit of detection was 0.03
      0.06 microg/L. Our method has proved linear up to 250 microg/L (r=0.999).
      Recoveries (S.D.) of 17-OHP, androstenedione and testosterone in plasma were 100%
      (5), 102% (2) and 92% (4), respectively. The regression equation for the LC-MS/MS
      (x) and immunoassay (y) methods for 17-OHP (excluding neonate samples) was
      y=1.942 x+0.255 nmol/L (r=0.695; n=97). In comparison to our values, the
      immunoassay generally overestimates steroid concentration. The regression
      equation for the LC-MS/MS (x) and immunoassay (y) methods for testosterone was
      y=0.963 x+0.035 nmol/L (r=0.955; n=107). Preliminary reference intervals for
      children were determined as a function of age and sex. The sensitivity and
      specificity of the LC-MS/MS method offer advantages over routine immunoassays due
      to the elimination of interferences especially for newborns, high throughput and
      short chromatographic run time.

PMID- 16569419
TI  - Maternal antibody inhibits both cellular and humoral immunity in response to
      measles vaccination at birth.
AB  - Maternal antibody prevents the use of live, attenuated measles vaccine (LAV)
      before 6-9 months of age, but vaccinated 6-month-old infants can mount a T cell
      response. An infant macaque model was used to study the immune response to LAV in
      the newborn in the presence or absence of maternal antibody. Four newborn monkeys
      without detectable maternal antibody and 9 newborns with passive measles antibody
      were vaccinated with LAV. Only the infants without passive antibody seroconverted
      after vaccination and 3 of 4 of these infants also developed measles-specific
      interferon gamma+ T cells. The monkeys were challenged with wild-type measles
      virus at 5 months of age, and 7 of 9 infants vaccinated in the presence of
      passive antibody had systemic infection and skin rash, while 3 of the 4 infants
      vaccinated in the absence of passive antibody were protected from viremia and
      rash. This suggests that the newborn can respond to LAV but that maternal
      antibody suppresses the priming of both humoral and cellular immunity at birth.

PMID- 16569418
TI  - Regio and stereoselective oxidations of unsaturated steroidal compounds with H2O2
      mediated by CH3ReO3.
AB  - We have investigated the oxidative behavior of sterols such as cholesteryl
      acetate (1), 7-dehydrocholesteryl acetate (2), ergosteryl acetate (3),
      cholecalciferol acetate (Vitamin D(3) acetate) (4) and ergocalciferol acetate
      (Vitamin D(2) acetate) (5) with the oxidant system
      methyltrioxorhenium/H(2)O(2)/pyridine in order to check potential parameters
      controlling the selectivity. The reactions, performed in CH(2)Cl(2)/H(2)O at 25
      degrees C, have shown good regio- and stereoselectivity. All oxidation products
      were isolated by high-performance liquid chromatography (HPLC) and characterized
      by MS(EI) or FAB, (1)H NMR, (13)C NMR, APT, COSY, HSQC, HMBC, ROESY and NOEDS
      measurements. Seven new oxygenated compounds were also obtained. Under the
      experimental conditions adopted in this work, only the diene steroids, i.e. 7
      dehydrocholesteryl acetate and ergosteryl acetate, undergo hydrolytic oxirane
      ring opening, whereas Vitamin D(2) and D(3) acetates, containing the triene
      system and cholesteryl acetate yield only epoxides. The selectivity seems to be
      controlled by the nucleophilicity of double bonds and by stereoelectronic and
      steric effects.

PMID- 16569420
TI  - Chelating properties and molecular weight distribution of soluble microbial
      products from an aerobic membrane bioreactor.
AB  - This paper presents a detailed study on soluble microbial products (SMPs) in an
      aerobic membrane bioreactor (MBR) treating synthetic wastewater simulating
      municipal wastewater. The concentration of SMP in the reactor conformed to a
      cyclical pattern of accumulation and reduction in relation to SRT. The molecular
      weight (MW) distribution of accumulated SMP was determined to vary from <1kD to
      >100kD. Copper chelating properties of various SMP fractions in the MBR were
      compared before and after copper addition to the feed. The conditional stability
      constant (LogcK), complexation capacity (Cc), and SMP-ligand concentration (CL)
      were evaluated to determine the impact of copper on the chelating properties. The
      results indicated that accumulated SMP in the aerobic MBRs without copper
      addition are moderate chelators with LogcK values of 7.6-8.3 mol(-1) for the
      moderate ligands and 6.3-6.8 mol(-1) for the relatively weaker ligands. SMPs with
      MW of 1-10 kD were found to have the highest complexation capacity among all SMP
      fractions. The complexation capacity of accumulated SMP after feeding copper was
      0.11 micromol/mg of SMP, almost half of its value prior to feeding copper. The
      reduction of C(c) after feeding copper was a result of an increase in large
      molecular weight SMP (>100 kD).

PMID- 16569421
TI  - The relative influence of the anthropogenic air pollutants on the atmospheric
      turbidity factors measured at an urban monitoring station.
AB  - This work is based on simultaneous measurements of direct solar radiation along
      with other chemical measurements, with the objective of investigating the diurnal
      and seasonal variations of atmospheric turbidity factors (i.e., Linke's factor,
      Angstrom's coefficient, and aerosol optical depth). Relationships between
      atmospheric turbidity factors, expressing the solar radiation extinction, and
      anthropogenic air pollutants were also evaluated. The frequency of occurrence of
      the individual indices has been established to describe the sky conditions. The
      preliminary results obtained indicate high variability of aerosol loading,
      leading to high turbidity for most of the year. Annual averages of 0.2 and 6 with
      standard deviations of 0.096 and 0.98 were found for Angstrom and Linke
      turbidities, respectively. On the base of the frequency of occurrence, it has
      been found that over 50% of the dataset are around 0.25 and 6.3 for Angstrom and
      Linke turbidities, respectively. On average, the month of September experienced
      the highest turbidity, while December experienced the lowest. A possible reason
      for this is that the vertical distribution of the aerosol particles moves up in
      September due to the extent of the Sudan monsoon trough. We also note that spring
      values of the turbidity factors are closer to summer values, whereas the
      pronounced difference between the summer values in comparison with the winter
      values may be attributed to relatively greater difference in the water vapor
      level in the atmosphere.

PMID- 16569422
TI  - Binding, distribution, and plant uptake of mercury in a soil from Oak Ridge,
      Tennessee, USA.
AB  - A large amount of mercury has been discharged on the U.S. Department of Energy's
      Oak Ridge Site (Tennessee) as a part of the U.S. nuclear weapon program during
      the 1950s through the early 1960s. Increases in mercury concentration in fish and
      in lower East Fork Poplar Creek of Oak Ridge have been recently reported. This is
      an experimental study mimicking the initial stage of transformation and
      redistribution of mercury in soils, which are comparable to those of the Oak
      Ridge site. The objectives of this study were to investigate potential
      transformation, distribution, and plant uptake of mercury compounds in soils.
      Results show that the H(2)O(2)-oxidizable mercury fraction (organically bound
      mercury) was the major solid-phase fraction in soils freshly contaminated with
      soluble mercury compounds, while cinnabar fraction was the major solid phase
      fraction in soils contaminated with HgS. Langmuir relationships were found
      between mercury concentrations in plant shoots and in soil solid-phase
      components. Mercury in HgS-contaminated soils was to some extent phytoavailable
      to plants. Mercury transformation occurred from more labile fractions into more
      stable fractions, resulting in strong binding of mercury and decreasing its
      phytoavailability in soils. In addition, high mercury losses from soils
      contaminated with soluble mercury compounds were observed during a growing season
      through volatilization, accounting for 20-62% of the total initial mercury in
      soils.

PMID- 16569423
TI  - Phagocytotic removal of apoptotic endocrine cells by folliculostellate cells and
      its functional implications in clusterin accumulation in pituitary colloids in
      helmeted guinea fowl (Numida meleagris).
AB  - The different cell types in the anterior pituitary behave as dynamic populations.
      The gland maintains a continuous renewal of cells to ensure a dynamic balance
      between cell division, differentiation, growth arrest and apoptosis. Apoptosis is
      a frequent event in the anterior pituitary in which unwanted cells are eliminated
      without affecting neighboring cells. We examined the link between apoptosis and
      the occurrence of colloids in the guinea fowl (Numida meleagris) pituitary gland
      and the relationship of clusterin accumulation in the colloids. S-100 positive
      folliculostellate (FS) cells were found surrounding colloids. Apoptotic cells
      detected by single stranded DNA (ssDNA) immunohistochemistry were observed in the
      whole anterior pituitary and preferentially near colloid masses. Clusterin
      protein was detected in endocrine cells, FS cells and in the colloids. In situ
      hybridization showed clusterin mRNA in endocrine cells and FS cells. Simultaneous
      localization was performed to determine whether clusterin mRNA and ssDNA within
      anterior pituitary was present within the same cell. Clusterin mRNA was not
      detected in apoptotic cells but was present in neighboring surviving cells. At
      the ultrastructural level, numerous endocrine cells at different stages of
      apoptosis were found phagocytosed by FS cells. Our results suggest that clusterin
      is produced by endocrine cells for cytoprotection before death. Apoptotic
      endocrine cells are phagocytosed by FS cells and digested by their lysosomal
      enzymes. In FS cells, clusterin interacts and aggregates with by-products of
      digestion that subsequently become stored in colloid as a residual body.

PMID- 16569424
TI  - Outcomes of women with metachronous breast and ovarian carcinomas.
AB  - INTRODUCTION: Women with a history of breast cancer have a significantly
      increased risk of developing a second primary ovarian cancer and vice versa. We
      proposed to determine the characteristics and outcomes of women diagnosed with
      metachronous breast and ovarian cancer. METHODS: Patients were identified from
      the Surveillance, Epidemiology, and End Results program database between 1988 and
      2001. Kaplan-Meier and Cox proportional hazards regression tests were used to
      determine survival outcomes. RESULTS: Of 704 women, 526 developed breast cancer
      then ovarian cancer (B-O) and 178 developed ovarian cancer then breast cancer (O
      B). The mean age at diagnosis of the first cancer in the B-O versus O-B group was
      60.3 versus 58.9 years, respectively (P = 0.23). Twenty-five percent of women in
      the B-O group had stage I-II ovarian cancer versus 63% in the O-B group (P <
      0.001). The percentage of those with stage I-II breast cancer was 94% and 91% in
      the B-O versus O-B group, respectively (P = 0.13). Women in the B-O group had
      more high grade of ovarian cancer compared to those in the O-B group (P < 0.001).
      The mean time interval between diagnoses of breast then ovarian versus ovarian
      then breast cancer was 58 versus 56 months, respectively (P = 0.42). CONCLUSIONS:
      In the largest series to date, we found that women diagnosed with ovarian cancer
      first had significantly more early stage and lower grade ovarian cancers with
      better survival compared to those with breast cancer followed by ovarian cancer.
      Since half of the women had their second cancer beyond 5 years, continued
      surveillance of these high risk patients is recommended.

PMID- 16569425
TI  - Antinociceptive activity of 3-O-beta-d-glucopyranosyl-23,24-dihydrocucurbitacin F
      from Hintonia standleyana (Rubiaceae).
AB  - Oral administration of a MeOH-CH(2)Cl(2) (1:1) extract of the stem bark of
      Hintonia standleyana (HSE) produced a dose-dependent antinociceptive effect when
      tested in mice using the writhing (150-750 mg/kg) and the hot-plate (150-600
      mg/kg) models. From the active extract 3-O-beta-d-glucopyranosyl-23,24
      dihydrocucurbitacin F (GDHCF), 5-O-[beta-d-apiofuranosyl-(1-->6)-beta-d
      glucopyranosyl]-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin (AG4-PC) and
      desoxycordifolinic acid (DCA) were isolated. GDHCF (10-100 mg/kg, p.o.)
      significantly reduced acetic acid-induced abdominal contortions and increased the
      hot-plate latency in comparison to vehicle-treated mice. Metamizol (50-100 mg/kg)
      and morphine (2.5-5 mg/kg) were used as positive controls, respectively. GDHCF
      induced antinociception was partially blocked by naloxone (1 mg/kg, i.p.), l-NAME
      (150 mg/kg, i.p.) and glibenclamide (10mg/kg, i.p.) suggesting that its
      pharmacological effect could be due to the activation of the nitric oxide
      pathway, followed by the opening of the ATP-sensitive K(+) channels, as well as
      an activation of the opioid receptors.

PMID- 16569426
TI  - Immunohistochemical localization of VEGF and its receptors in the corpus luteum
      of the bitch during diestrus and anestrus.
AB  - The corpus luteum (CL) is a temporary endocrine gland, whose life span depends on
      the interaction of luteotrophic and luteolytic factors. Since development and
      maintenance of CL is based on angiogenesis, angiogenic growth factors may play a
      role in CL-function of the bitch, as described for other species. The aim of this
      study was to detect the presence of the vascular endothelial growth factor (VEGF)
      system in the bitch CL throughout diestrus and early anestrus. For that purpose,
      blood samples from 24 bitches were collected and analyzed for progesterone to
      determine ovulation time and the animals were subjected to
      ovariosalpingohysterectomy 10, 20, 30, 40, 50, 60 or 70 days after ovulation. The
      corpora lutea were fixed in formalin and embedded in Paraplast resin. Five
      micrometers sections were submitted to standard immunohistochemistry protocol
      using three primary antibodies (SC-315, SC-316 and VG76e) for detection of kinase
      domain region (KDR), fms-like tyrosine kinase 1 (Flt-1) and VEGF, respectively.
      The VEGF system expression could be detected in all diestrus stages in
      endothelial as well as luteal cells (responsible for blood vessel formation and
      progesterone production, respectively), indicating time dependent changes:
      immunostaining tended to increase from Day 10 to 50 and to decrease until Day 70
      post-ovulation. In the CL of the bitch, structure related cells, like pericytes
      and stroma cells, expressed it in determined time points of diestrus with little
      intensity variation. We concluded that VEGF might have a modulatory effect in the
      CL of the dog acting as paracrine and autocrine factor through its receptors, Flt
      1 and KDR.

PMID- 16569427
TI  - Improving the initial biocompatibility of a titanium surface using an Er,Cr:YSGG
      laser-powered hydrokinetic system.
AB  - OBJECTIVES: This study was designed to improve the initial biocompatibility of
      titanium (Ti) using an Er,Cr:YSGG-powered hydrokinetic system. METHODS: The
      Er,Cr:YSGG-powered hydrokinetic system with different laser energy densities, 125
      and 190 J/cm(2), were applied to the Ti substrate. Human osteosarcoma U2-OS cells
      were used. The difference in the attached cell number between 3- and 1-days cell
      culture was calculated and defined as the initial cell proliferation index (CPI).
      The initial CPI was statistically analyzed using one-way analysis of variance
      with the factor of applied laser energy density. The surface spreading morphology
      of the attached cells after 1 day incubation was observed using a field-emission
      scanning electron microscope. RESULTS: The Er,Cr:YSGG laser-treated Ti had a
      higher (1.2-1.3 times) initial CPI (P<0.001) and better cell spreading morphology
      than the untreated Ti. Treating the Ti with higher Er,Cr:YSGG laser energy did
      not significantly improve the CPI and cell spreading morphology. SIGNIFICANCE:
      The initial biocompatibility of the Ti surface could be improved using an
      Er,Cr:YSGG laser-powered hydrokinetic system.

PMID- 16569428
TI  - Binding of all-trans retinoic acid to human serum albumin: fluorescence, FT-IR
      and circular dichroism studies.
AB  - All-trans retinoic acid derived from vitamin A is an essential component for the
      modulation of angiogenesis, the process of blood vessel formation. We have
      investigated the binding of all-trans retinoic acid to the carrier protein, human
      serum albumin (HSA) under physiological conditions. Fluorescence quenching
      methods in combination with Fourier transform infrared (FT-IR) spectroscopy and
      circular dichroism (CD) spectroscopy were used for the biophysical studies. The
      binding parameters were determined by a Scatchard plot and the results found to
      be consistent with those obtained from a modified Stern-Volmer equation. From the
      thermodynamic parameters calculated according to the van't Hoff equation, the
      enthalpy change DeltaH(0) and entropy change DeltaS(0) are found to be 106.17 and
      106.14J/molK, respectively. These values suggest that apart from hydrophobic
      interactions electrostatic interactions are present. Changes in the CD spectra
      and FT-IR spectra were observed upon ligand binding along with a significant
      degree of tryptophan fluorescence quenching on complex formation. Docking studies
      performed substantiated our experimental findings and it was observed that all
      trans retinoic acid hydrogen bonded with Trp 214 and Asp 451 residues of
      subdomain IIA and IIIA of HSA, respectively.

PMID- 16569430
TI  - Integrin beta1 silencing in osteoblasts alters substrate-dependent responses to
      1,25-dihydroxy vitamin D3.
AB  - Surface microroughness increases osteoblast differentiation and enhances
      responses of osteoblasts to 1,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3]. The
      observations that beta1 integrin expression is increased in osteoblasts grown on
      Ti substrates with rough microarchitecture, and that it is regulated by
      1alpha,25(OH)2D3 in a surface-dependent manner, suggest that beta1 may play a
      role in mediating osteoblast response. To test this hypothesis, we silenced beta1
      expression in MG63 human osteoblast-like cells using small interfering RNA
      (siRNA) and examined the responses of the beta1-silenced osteoblasts to surface
      microtopography and 1alpha,25(OH)2D3. To better understand the role of beta1,
      MG63 cells were also treated with two different monoclonal antibodies to human
      beta1 to block ligand binding. beta1-silenced MG63 cells grown on a tissue
      culture plastic had reduced alkaline phosphatase activity and levels of
      osteocalcin, transforming growth factor beta1, prostaglandin E2, and
      osteoprotegerin in comparison with control cells. Moreover, beta1-silencing
      inhibited the effects of surface roughness on these parameters and partially
      inhibited effects of 1alpha,25(OH)2D3. Anti beta1 antibody AIIB2 had no
      significant effect on cell number and osteocalcin, but decreased alkaline
      phosphatase; MAB2253Z caused dose-dependent decreases in cell number and alkaline
      phosphatase and an increase in osteocalcin. Effects of 1alpha,25(OH)2D3 on cell
      number and alkaline phosphatase were reduced and effects on osteocalcin were
      increased. These findings indicate that beta1 plays a major and complex role in
      osteoblastic differentiation modulated by either surface microarchitecture or
      1alpha,25(OH)2D3. The results also show that beta1 mediates, in part, the
      synergistic effects of surface roughness and 1alpha,25(OH)2D3.

PMID- 16569429
TI  - The differentiation of bone marrow mesenchymal stem cells into chondrocyte-like
      cells on poly-L-lactic acid (PLLA) scaffolds.
AB  - While intervertebral disc (IVD) degeneration is associated with the majority of
      cases of low back pain, current treatments are symptomatic rather than curative.
      Tissue engineering offers a treatment that both cures the problem of disc
      degeneration and restores normal disc function. One of the major problems for any
      tissue engineering strategy, however, is ensuring that both the cells and
      matrices used are suitable for the target tissue. In this study, we have
      developed and studied a potential system for tissue engineering of the nucleus
      pulposus (NP) of the severely degenerate IVD. While cells from degenerate discs
      are not suitable for tissue engineering, bone-marrow-derived mesenchymal stem
      cells, which are capable of differentiating into chondrocyte-like cells such as
      those found within the NP of the disc, offer a potential source of cells. We have
      used transfection with adenoviral SOX-9, a transcription factor involved in
      differentiation of MSCs along the chondrogenic lineage, combined with culture in
      a specialised medium, to differentiate monolayer MSCs to NP-like (chondrocyte
      like) cells, as shown by real-time quantitative polymerase chain reaction for NP
      marker genes. We have also replicated these findings on porous, biodegradable
      three-dimensional (3D) poly-l-lactic acid scaffolds and shown expression and
      deposition of NP matrix markers such as type II collagen and aggrecan. We are
      therefore proposing pre-differentiation of human MSCs and seeding on porous,
      biodegradable 3D synthetic polymer scaffolds as a realistic tissue engineering
      strategy for regeneration of the degenerate human IVD.

PMID- 16569432
TI  - Multifocal cutaneous leishmaniasis.

PMID- 16569431
TI  - Changes in immune gene expression and resistance to bacterial infection in
      lobster (Homarus gammarus) post-larval stage VI following acute or chronic
      exposure to immune stimulating compounds.
AB  - Real-time PCR was used to measure changes in transcript abundance of genes
      encoding important immune proteins, namely prophenoloxidase (proPO gene), beta
      1,3-glucan binding protein (betaGBP gene) and a 12.2 kDa antimicrobial peptide
      (amp gene) in post-larval stage VI (PLVI) juveniles of the European lobster,
      Homarus gammarus. Gene expression was studied in both healthy PLVI and following
      single or repeat exposure to a range of compounds claimed to induce immune
      reactivity. A single acute (3-h) exposure to any of the tested stimulants did not
      produce a significant increase in expression of either the proPO or betaGBP
      genes, measured 6h after stimulation. However, there were a small sub-group of
      positive responders, identified mainly from betaGBP expression, within the
      experimental groups stimulated with either a beta-1,3-glucan or an alginate.
      There was also no significant increase in the expression of any of the three
      genes tested 24 h after repeated weekly (3-h) exposures to a either the beta-1,3
      glucan or the alginate over the longer (36-day) period. The results do show that
      amp is expressed at an extremely high level compared to proPO or betaGBP in
      healthy animals and a significant correlation was found between the expression of
      proPO and both betaGBP and amp, irrespective of whether or not the larvae were
      stimulated. None of the immune stimulated compounds improved survival of PLVI
      challenged with the opportunistic pathogen, Listonella anguillarum, or the
      lobster pathogen, Aerococcus viridans var. homari. Thus, we found no evidence to
      support recent claims that immunity and disease resistance can be primed or
      promoted within a given population of crustaceans or that these animals exhibit
      functional immune memory to some soluble immune elicitors.

PMID- 16569433
TI  - Changes in the distribution of hepatitis C virus (HCV) genotypes over time in
      Spain according to HIV serostatus: implications for HCV therapy in HCV/HIV
      coinfected patients.
AB  - BACKGROUND: Changes in the prevalence of distinct hepatitis C virus (HCV)
      genotypes and subtypes over time have not been explored in detail. METHODS: A
      retrospective analysis was carried out in all specimens from subjects with
      chronic hepatitis C sent for testing to a reference laboratory in Spain since
      1998-2004. RESULTS: A total of 1226 distinct subjects were analyzed. The most
      frequent HCV genotype was 1 (64.1%), followed by 3 (20.9%) and 4 (11.7%). The
      most frequent HCV subtype was 1b (32.4%). A total of 797 patients (65%) were HIV
      positive. Although genotype 1 was the most frequent, it represented 74.6% of HIV
      negative and 58.5% of HIV-positive patients (p<0.01). While HCV subtype 1a was
      the most frequent among HIV-positive subjects (32.1%), 1b was the most common in
      HIV-negative patients (53.8%). There was a significant increase in the prevalence
      of genotype 4 and conversely a decline in genotype 3 among HIV-positive patients
      over time. CONCLUSION: Genotype 1 is the most frequent HCV variant circulating in
      Spain. Genotypes 3 and 4 are significantly more prevalent in HIV/HCV-coinfected
      than in HCV-monoinfected patients. However, HCV-3 has declined and HCV-4 is
      increasing in the former group. These findings are relevant given their different
      susceptibility to interferon-based therapies.

PMID- 16569434
TI  - Morganella morganii pericarditis 3 years after allogenic bone marrow
      transplantation for mantle cell lymphoma.
AB  - We report herein a case of Morganella morganii-associated acute purulent
      pericarditis that developed 3 years after allogenic bone marrow transplantation.
      The patient was successfully treated with surgical drainage and cefotaxime for 6
      weeks. Splenectomy and immunosuppression for chronic GVH-D are likely to have
      favored the development of this rare infectious complication after BMT. M.
      morganii should be added to the list of bacteria causing purulent pericarditis,
      especially in immunocompromised hosts.

PMID- 16569435
TI  - Aspergillus thyroiditis in a living donor liver transplant recipient.
AB  - Aspergillosis is increasingly recognized as an important nosocomial pathogen in
      immunocompromised patients. Infection is difficult to diagnose and typically has
      a fatal outcome. We describe a liver transplant patient with fulminant hepatic
      failure, who had persistent fever of undetected origin postoperatively and an
      increased (1-3)-beta-d glucan level. Gallium-67 citrate scanning showed abnormal
      uptake in the thyroid bilaterally. Fine needle biopsy of the thyroid revealed
      thyroidal invasion of Aspergillosis. Total thyroidectomy was performed and the C
      reactive protein level decreased to 1.01 mg/dl. The patient died of liver sepsis
      due to Pseudomonas aeruginosa. (1-3)-beta-d Glucan monitoring and systematic
      radionuclide images are useful modalities for early diagnosis of Aspergillosis.

PMID- 16569436
TI  - Comparison of silicon-coated nylon suture to plain nylon suture in the rat middle
      cerebral artery occlusion model.
AB  - A variety of intraluminal sutures have been used in the middle cerebral artery
      occlusion model (MCAO) of focal ischemia. In the present study we tested
      commercially available silicon-coated nylon suture in the MCAO model and compared
      the results to traditional monofilament nylon suture occlusion. Twelve Sprague
      Dawley male rats were randomly divided two groups, MCAO with 4-0 nylon suture
      (Group N, n=6) and MCAO with silicone-coated 4-0 nylon suture (Group S, n=6).
      Rats were sacrificed 24 h after reperfusion. Assessment included mortality rates,
      neurological evaluation, and infarct volume. One rat died in each group from
      subarachanoid hemorrhage. Neurological evaluation demonstrated that Group S
      tended to have worse neurological outcomes than Group N, although this difference
      was not statistically significant. On TTC stain Group S had significantly larger
      infarct volumes than Group N. We conclude that the commercially available
      silicone-coated occlusion suture provides better occlusion of the middle cerebral
      artery than the traditional uncoated nylon suture. CLASSIFICATION: Disease
      related neuroscience (Section 6).

PMID- 16569437
TI  - A volumetric MRI study of the hippocampus and the parahippocampal region after
      unilateral medial temporal lobe resection.
AB  - Segmentation guidelines on high-resolution MRI designed to assess remaining
      volumes of the hippocampus and the parahippocampal cortices after medial temporal
      lobe (MTL) surgery could provide a useful tool to investigate the involvement of
      these anatomical regions in surgical outcomes and in human memory. For this
      purpose, we implemented an MRI volumetric analysis, already applied to healthy
      population or epileptic patient before surgery, to quantify the volume of the
      hippocampus, the temporopolar cortex and the regions of the parahippocampal gyrus
      (perirhinal, entorhinal and parahippocampal cortices) spared after unilateral MTL
      resection carried out to treat medically uncontrolled temporal lobe epilepsy
      (TLE). Based on the locations of remaining anatomical landmarks, we quantified
      the volume of these regions in 24 patients after MTL resection and in 16 control
      participants. Our results show that (1) mean volumes of these regions
      contralateral to the epileptic focus were similar to those of normal subjects,
      (2) volumetric measures obtained from the resected side were much smaller than
      those from the non-resected side or from normal values and (3) the extent of MTL
      resection was comparable in right or left MTL surgery. Individual analysis of
      patients showed that the parahippocampal cortex, as opposed to the other regions,
      was not systematically removed across patients. As a post-operative MRI-based
      method, it therefore proves valuable to assess group data as well as to explore
      differences between individual patients.

PMID- 16569438
TI  - Homeopathy: the case in favour.

PMID- 16569439
TI  - An efficient helper-virus-free method for rescue of recombinant paramyxoviruses
      and rhadoviruses from a cell line suitable for vaccine development.
AB  - Recovery of recombinant, negative-strand, nonsegmented RNA viruses from a genomic
      cDNA clone requires a rescue system that promotes de novo assembly of a
      functional ribonucleoprotein (RNP) complex in the cell cytoplasm. This is
      accomplished typically by cotransfecting permissive cells with multiple plasmids
      that encode the positive-sense genomic RNA, the nucleocapsid protein (N or NP),
      and the two subunits of the viral RNA-dependent RNA polymerase (L and P). The
      transfected plasmids are transcribed in the cell cytoplasm by phage T7 RNA
      polymerase (T7 RNAP), which usually is supplied by infection with a recombinant
      vaccinia virus or through use of a stable cell line that expresses the
      polymerase. Although both methods of providing T7 RNAP are effective neither is
      ideal for viral vaccine development for a number of reasons. Therefore, it was
      necessary to modify existing technology to make it possible to routinely rescue a
      variety of recombinant viruses when T7 RNAP was provided by a cotransfected
      expression plasmid. Development of a broadly applicable procedure required
      optimization of the helper-virus-free methodology, which resulted in several
      modifications that improved rescue efficiency such as inclusion of plasmids
      encoding viral glycoproteins and matrix protein, heat shock treatment, and use of
      electroporation. The combined effect of these enhancements produced several
      important benefits including: (1) a helper-virus-free methodology capable of
      rescuing a diverse variety of paramyxoviruses and recombinant vesicular
      stomatitis virus (rVSV); (2) methodology that functioned effectively when using
      Vero cells, a suitable substrate for vaccine production; and (3) a method that
      enabled rescue of highly attenuated recombinant viruses, which had proven
      refractory to rescue using published procedures.

PMID- 16569440
TI  - Inhibition of HIV entry by carbohydrate-binding proteins.
AB  - Carbohydrate-binding proteins (CBP) can be isolated from a variety of species,
      including procaryotes (i.e. cyanobacteria), sea corals, algae, plants,
      invertebrates and vertebrates. A number of them, in particular those CBP that
      show specific recognition for mannose (Man) and N-acetylglucosamine (GlcNAc) are
      endowed with a remarkable anti-HIV activity in cell culture. The smallest CBP
      occur as monomeric peptides with a molecular weight of approximately 8.5 kDa.
      Many others are functionally dimers, trimers or tetramers, and their molecular
      weight can sometimes largely exceed 50 kDa. CBP can contain 2 to up to 12
      carbohydrate-binding sites per single molecule, depending on the nature of the
      lectin and its oligomerization state. CBP qualify as potential anti-HIV
      microbicide drugs because they not only inhibit infection of cells by cell-free
      virus (in some cases in the lower nano- or even subnanomolar range) but they can
      also efficiently prevent virus transmission from virus-infected cells to
      uninfected T-lymphocytes. Their most likely mechanism of antiviral action is the
      interruption of virus entry (i.e. fusion) into its target cell. CBP presumably
      act by direct binding to the glycans that are abundantly present on the HIV-1
      gp120 envelope. They may cross-link several glycans during virus/cell interaction
      and/or freeze the conformation of gp120 consequently preventing further
      interaction with the coreceptor. Several CBP were shown to have a high genetic
      barrier since multiple (>or=5) glycan deletions in the HIV envelope are necessary
      to provoke a moderate level of drug resistance. CBP are the prototypes of
      conceptionally novel chemotherapeutics with a unique mechanism of antiviral
      action, drug resistance profile and an intrinsic capacity to trigger a specific
      immune response against HIV strains after glycan deletions on their envelope
      occur in an attempt to escape CBP drug pressure.

PMID- 16569441
TI  - Moderate iron deficiency in infancy: biology and behavior in young rats.
AB  - Iron deficiency anemia in early childhood is associated with developmental delays
      and perhaps, irreversible alterations in neurological functioning. The goals were
      to determine if dietary induced gestational and lactational iron deficiency
      alters brain monoamine metabolism and behaviors dependent on that
      neurotransmitter system. Young pregnant rats were provided iron deficient or
      control diets from early in gestation through to weaning of pups and brain iron
      concentration, regional monoamine variables and achievement of specific
      developmental milestones were determined throughout lactation. Despite anemia
      during lactation, most brain iron concentrations did not fall significantly until
      P25, and well after significant changes in monoamine levels, transporter levels,
      and D2R density changed in terminal fields. The changes in D2R density were far
      smaller than previously observed models that utilized severe dietary restriction
      during lactation or after weaning. Iron deficient pups had normal birth weight,
      but were delayed in the attainment of a number of milestones (bar holding,
      vibrissae-evoked forelimb placing). This approach of iron deficiency in utero and
      during lactation sufficient to cause moderate anemia but not stunt growth
      demonstrates that monaminergic metabolism changes occur prior to profound
      declines in brain iron concentration and is associated with developmental delays.
      Similar developmental delays in iron deficient human infants suggest to us that
      alterations in iron status during this developmental period likely affects
      developing brain monaminergic systems in these infants.

PMID- 16569442
TI  - Thalamic and hippocampal mechanisms in spatial navigation: a dissociation between
      brain mechanisms for learning how versus learning where to navigate.
AB  - Various studies of hippocampus and medial thalamus (MT) suggest that these brain
      areas play a crucial, marginal, or no essential role in spatial navigation. These
      divergent views were examined in experiments using electrolytic Lesions of
      fimbria-fornix (FF) or radiofrequency or neurotoxic Lesions of MT of rats
      subsequently trained to find a stable visible (experiment 1) or hidden platform
      (experiments 2 and 3) in a water maze (WM) pool. Rats with electrolytic Lesions
      of FF or radiofrequency Lesions of MT were impaired in swimming to a stable
      visible platform, particularly the MT Lesion Group, suggesting impairment of WM
      strategies acquisition. Additional Lesioned rats were then tested in a hidden
      platform version of the WM task. Some rats were given Morris's nonspatial
      pretraining prior to Lesioning to provide them with training in the required WM
      behavioral strategies. Nonspatially Pretrained rats with FF Lesions eventually
      were able to navigate to the hidden platform, but the accuracy of place
      responding was impaired. This impairment occurred without problems in the motoric
      control of swimming or the use of WM behavioral strategies, suggesting that these
      rats had a spatial mapping impairment. Radiofrequency MT Lesions blocked
      acquisition of WM behavioral strategies by Naive rats throughout 3 days of
      training, severely impairing performance on all aspects of the hidden platform
      task. Nonspatially Pretrained rats given the same MT Lesions readily learned the
      hidden platform location and were indistinguishable from controls throughout
      spatial training. Rats given neurotoxic Lesions of MT for removal of cells were
      only mildly impaired and improved considerably during training, suggesting an
      important role for fibers of passage in WM strategies learning. The results
      provide a clear dissociation between a role for MT in learning WM behavioral
      strategies and the hippocampal formation in spatial mapping and memory. This is
      the first identification of a brain area, MT, that is essential for learning
      behavioral strategies that by themselves do not constitute the solution to the
      task but are necessary for the successful use of an innate learning ability:
      place response learning using spatial mapping.

PMID- 16569443
TI  - Distribution of Fos immunoreactivity in the rat brain after freezing or escape
      elicited by inhibition of glutamic acid decarboxylase or antagonism of GABA-A
      receptors in the inferior colliculus.
AB  - It has been shown that electrical stimulation of the central nucleus of the
      inferior colliculus (IC) at freezing or escape thresholds activates different
      neural circuits in the brain. Since electrical stimulation activates cell bodies
      and fibers of passage it is necessary to use chemical stimulation that activates
      only post-synaptic receptors. To examine this issue in more detail, we took
      advantage of the fact that GABAergic neurons exert tonic control over the neural
      substrates of aversion in the IC. Reduction of GABA transmission in this
      structure was performed with the use of semicarbazide - an inhibitor of the GABA
      synthesizing enzyme glutamic acid decarboxylase (GAD) - and the GABA-A receptor
      antagonist bicuculline. Depending on the dose employed local infusions of
      semicarbazide (6.0 microg/0.2 microl) or bicuculline (40 ng/0.2 microl) into this
      region caused freezing and escape, respectively. The results obtained showed that
      freezing behavior induced by semicarbazide was associated with an increase in Fos
      expression in the dorsomedial column of the PAG (dmPAG) only, while bicuculline
      induced escape was related to widespread increase in Fos labeling, notably in the
      periaqueductal gray, hypothalamus nuclei, amygdaloid nuclei, the laterodorsal
      nucleus of thalamus (LD), the cuneiform nucleus (CnF) and the locus coeruleus
      (LC). Thus, the present data support the notion that freezing and escape
      behaviors induced by GABA blockade in the IC are neurally segregated: acquisition
      of aversive information of acoustic nature from the IC probably uses the dmPAG
      column as a relay station to higher brain centers whereas bicuculline-induced
      escape activates structures involved in both sensory processing and motor output
      of defensive behavior. These results support the existence of distinct neural
      circuits mediating the sensory and motor responses of the defense reaction. The
      extent of the brain activation during freezing appears to be limited to the
      anatomical connections of the dmPAG, whereas an overall activation of the limbic
      system predominates during escape behavior induced by IC stimulation.

PMID- 16569444
TI  - Laterality of flipper rubbing behaviour in wild bottlenose dolphins (Tursiops
      aduncus): caused by asymmetry of eye use?
AB  - To determine whether wild Indo-Pacific bottlenose dolphins (Tursiops aduncus) at
      Mikura Island, Japan, show asymmetry of eye or flipper use during a social
      behaviour, we investigated the laterality of flipper-to-body (F-B) rubbing, in
      which one dolphin ("rubber") rubs the body of another ("rubbee") with its
      flipper. We analysed 382 episodes of video-recorded F-B rubbings performed by
      identified individuals (N=111 rubbers). F-B rubbing was conducted significantly
      more frequently with the left flipper than with the right flipper. The duration
      of F-B rubbings was also significantly longer with the left flipper than with the
      right flipper. Of 20 dolphins, nine individuals showed significant left-side bias
      as the rubber in this behaviour, whereas no dolphins showed significant right
      side bias. The results indicate a population-level left-side bias of the rubber
      in F-B rubbing. An analysis of the swimming configurations during this behaviour
      suggests that the asymmetry in F-B rubbing was caused not only by the laterality
      of the rubber, but by a preference for use of the left eye in both dolphins
      during this behaviour. Dolphins used the left eye significantly more frequently
      than the right eye during the inquisitive behaviour, while they showed no
      significant bias in flipper use during the object-carrying behaviour. These facts
      also suggest that the asymmetry of F-B rubbing is caused by the preference for
      using the left eye. Significant left-side bias was observed only in F-B rubbings
      initiated by the rubbee, in which the rubbee determined its position during this
      behaviour. This suggests that this behavioural asymmetry was enhanced by the
      rubbees choosing the left side of the rubber to ensure better and longer rubs.

PMID- 16569445
TI  - Startle and prepulse inhibition as a function of background noise: a
      computational and experimental analysis.
AB  - Schmajuk and Larrauri [Schmajuk NA, Larrauri JA. Neural network model of prepulse
      inhibition. Behav Neurosci 2005;119:1546-62.] introduced a real-time model of
      acoustic startle, prepulse inhibition (PPI) and facilitation (PPF) in animals and
      humans. The model assumes that (1) positive values of changes in noise level
      activate an excitatory and a facilitatory pathway, and (2) absolute values of
      changes in noise level activate an inhibitory pathway. The model describes many
      known properties of the phenomena and the effect of brain lesions on startle,
      PPI, and PPF. The purpose of the present study is to (a) establish the magnitude
      of startle and PPI as a function of pulse, prepulse, and background intensity,
      and (b) test the model predictions regarding an inverted-U function that relates
      startle to the intensity of the background noise.

PMID- 16569447
TI  - Prior electrical stimulation of dorsal periaqueductal grey matter or deep layers
      of the superior colliculus sensitizes rats to anxiety-like behaviors in the
      elevated T-maze test.
AB  - Electrical stimulation of the dorsal periaqueductal grey matter (DPAG) and deep
      layers of the superior colliculus (DLSC) of the rat elicits anxiety-like
      reactions such as freezing and flight. The temporal course of the effects of the
      aversive electrical stimulation of the DPAG (5, 15 and 30 min afterward) and DLSC
      (5, 10 and 15 min afterward) on the defensive response of rats exposed to
      elevated T-maze were determined. The elevated T-maze generates two defensive
      behaviors, inhibitory avoidance and one-way escape, which have been related,
      respectively, to generalized anxiety and panic disorders. Prior electrical
      stimulation of the DPAG (15 min) and DLSC (5 min) enhanced inhibitory avoidance
      when compared to no-operated and sham animals, although not affecting escape.
      Therefore, stimulation of the DPAG and DLSC causes a heightened responsivity to
      anxiogenic stimulus, but not to panicogenic stimulus, inherent to elevated T
      maze. These findings support the participation of the DPAG and DLSC in the
      elaboration of adaptive responses to stressful situations. Besides, the data
      supports the view that prior electrical stimulation of DPAG and DLSC is selective
      in sensitizing rats to anxiety-like behaviors, but not to panic-like behaviors in
      the elevated T-maze test.

PMID- 16569446
TI  - Progressive deterioration of reaction time performance and choreiform symptoms in
      a new Huntington's disease transgenic ratmodel.
AB  - We tested the hypothesis that a recently developed transgenic rat model of
      Huntington's disease (tgHD rats) showed an age-and genotype-dependent change in
      psychomotor performance and in the frequency of choreiform movements similar to
      HD patients. Wild type and tgHD (homozygotic and heterozygotic) rats were
      behaviorally tested at an age of 15 and 20 months. Our results show that tgHD
      rats exhibit an age-, and genotype-dependent deterioration of the psychomotor
      performance and choreiform symptoms, closely mimicking the clinical time course
      changes of psychomotor symptoms of HD patients. These data provide further
      experimental evidence that the tgHD rat can be considered as a relevant animal
      model of HD.

PMID- 16569448
TI  - Environmental context determines nitrate toxicity in Southern toad (Bufo
      terrestris) tadpoles.
AB  - Aquatic nitrate contamination has escalated over the past 50 years, primarily due
      to intensified fertilizer application and sewage production worldwide. Nitrate's
      role in the decline of amphibian populations remains unclear, although studies
      suggest that nitrate exposure affects larval development. We exposed Bufo
      terrestris tadpoles to environmentally relevant nitrate concentrations from
      Gosner stage 25 through forelimb emergence. Tadpoles were exposed to fluctuating
      (0-30 mg/L NO(3)-N, alternated three times per week) or constant nitrate
      concentrations (0, 5, 15, or 30 mg/L NO(3)-N), and effects were compared in two
      water types: natural spring water and reverse-osmosis filtered water, fortified
      with electrolytes (RO(e)). We measured growth and developmental rates, survival,
      time to metamorphosis, metamorph body size, hepatosomatic index, and whole-body
      thyroxine (T(4)) concentrations at forelimb emergence. Based on our observations,
      we reached three main conclusions: (1) in constant nitrate, tadpoles in RO(e)
      water grew faster, and were generally larger with higher or similar T(4) at
      metamorphosis than tadpoles raised in spring water, irrespective of nitrate
      concentration, (2) in fluctuating nitrate (flux), there were no differences in
      time to or size at metamorphosis in either water type relative to controls;
      however, mean T(4) concentrations in the flux treatment showed a reversed pattern
      in the two water types (SP>RO(e)) compared to the general pattern observed with
      constant nitrate exposure (RO(e)>SP), and (3) the effect of nitrate on growth and
      development depended on water type. In RO(e) water with high nitrate (RO(e)-30
      mg/L NO(3)-N), tadpoles metamorphosed an average of 5 days (13%) earlier than
      control animals, but were similar in size to controls. However, spring water
      tadpoles reared in high nitrate (30 mg/L) delayed metamorphosis by 7 days (18%)
      compared to animals reared in SP-0, and 11 days (32%) compared to tadpoles raised
      in RO(e)-30. This delayed development allowed SP-30 tadpoles to reach a larger
      size that was more similar to metamorphs raised in RO(e) water. Based on
      information from other studies, we conclude that, in RO(e) water, tadpoles
      exhibited an expected stress response to nitrate (e.g. metamorphosed earlier as
      nitrate concentration increased). However, we suggest that, in spring water,
      tadpoles were exposed to additional stressors that decreased growth rate and
      thyroxine concentrations, and that this effect was modified by nitrate.

PMID- 16569449
TI  - Impact of intestinal colonization and invasion on the Entamoeba histolytica
      transcriptome.
AB  - A genome-wide transcriptional analysis of Entamoeba histolytica was performed on
      trophozoites isolated from the colon of six infected mice and from in vitro
      culture. An Affymetrix platform gene expression array was designed for this
      analysis that included probe sets for 9435 open reading frames (ORFs) and 9066 5'
      and 3' flanking regions. Transcripts were detected for > 80% of all ORFs. A total
      of 523 transcripts (5.2% of all E. histolytica genes) were significantly changed
      in amebae isolated from the intestine on Days 1 and 29 after infection: 326 and
      109 solely on Days 1 and 29, and 88 on both days. Quantitative real-time reverse
      transcriptase PCR confirmed these changes in 11/12 genes tested using mRNA
      isolated from an additional six mice. Adaptation to the intestinal environment
      was accompanied by increases in a subset of cell signaling genes including
      transmembrane kinases, ras and rho family GTPases, and calcium binding proteins.
      Significant decreases in mRNA abundance for genes involved in glycolysis and
      concomitant increases in lipases were consistent with a change in energy
      metabolism. Defense against bacteria present in the intestine (but lacking from
      in vitro culture) was suggested by alterations in mRNA levels of genes similar to
      the AIG1 plant antibacterial proteins. Decreases in oxygen detoxification
      pathways were observed as expected in the anaerobic colonic lumen. Of the known
      virulence factors the most remarkable changes were a 20-35-fold increase in a
      cysteine proteinase four-like gene, and a 2-3-fold decrease in two members of the
      Gal/GalNAc lectin light subunit family. Control of the observed changes in mRNA
      abundance in the intestine might potentially rest with four related proteins with
      DNA binding domains that were down-regulated 6-16-fold in the intestinal
      environment. In conclusion, the first genome-wide analysis of the transcriptome
      of E. histolytica demonstrated that the vast majority of genes are transcribed in
      trophozoites, and that in the host intestine trophozoites altered the expression
      of mRNAs for genes implicated in metabolism, oxygen defense, cell signaling,
      virulence, antibacterial activity, and DNA binding.

PMID- 16569450
TI  - Functional characterisation of a nematode secreted GM2-activator protein.
AB  - We have identified a GM2-activator protein (GM2AP) with highly unusual properties
      secreted by the nematode parasite Trichinella spiralis. Expression in Pichia
      pastoris resulted in a hyperglycosylated protein of 28 kDa, but the 18 kDa native
      protein was not glycosylated. The parasite GM2AP does not facilitate degradation
      of GM2 ganglioside by N-acetyl-beta-hexosaminidase A, although it does inhibit
      phospholipase D activity. Lack of the former activity might be explained by the
      absence of a domain implicated in binding to hexosaminidase. In addition, and
      contrary to data on the human GM2AP, the nematode homologue does not inhibit
      platelet activating factor-induced calcium mobilisation in neutrophils, but
      actually enhances mediator-induced chemotaxis.

PMID- 16569452
TI  - Cirp protects against tumor necrosis factor-alpha-induced apoptosis via
      activation of extracellular signal-regulated kinase.
AB  - Mild hypothermia shows protective effects on patients with brain damage and
      cardiac arrest. To elucidate the molecular mechanisms underlying these effects,
      we analyzed the effects of low culture temperature (32 degrees C) and cold
      inducible RNA-binding protein (Cirp) expression on apoptosis in vitro. In
      BALB/3T3 cells treated with tumor necrosis factor (TNF)-alpha and cycloheximide,
      the down-shift in temperature from 37 degrees C to 32 degrees C increased the
      expression of Cirp and suppressed the apoptosis. Activation of caspase-8 was
      suppressed, and the level of phosphorylated extracellular signal-regulated kinase
      (ERK) was increased. Transduction of Cirp into the Cirp-deficient mouse
      fibroblasts increased the level of phosphorylated ERK and suppressed the TNF
      alpha-induced apoptosis both at 37 degrees C and 32 degrees C. The ERK-specific
      inhibitor PD98059 decreased the cytoprotective effect of Cirp as well as that of
      low culture temperature. These data suggest that mild hypothermia protects cells
      from TNF-alpha-induced apoptosis, at least partly, via induction of Cirp, and
      that Cirp protects cells by activating the ERK pathway.

PMID- 16569451
TI  - The suppression of galactose metabolism in Trypanosoma cruzi epimastigotes causes
      changes in cell surface molecular architecture and cell morphology.
AB  - The cell surface of the epimastigote form of Trypanosoma cruzi is covered by
      glycoconjugates rich in galactose. The parasite cannot take up galactose through
      its hexose transporter, suggesting that the epimerisation of UDP-glucose to UDP
      galactose may be the parasite's only route to this sugar. The T. cruzi UDP
      glucose 4'-epimerase is encoded by the TcGALE gene. We were unable to make a CL
      Brener strain T. cruzi epimastigote TcGALE-/- null mutant, suggesting that the
      gene is essential. Two TcGALE+/- single-allele knockout clones displayed aberrant
      morphology and haploid deficiency with respect to galactose metabolism. The
      morphological phenotypes included shortened flagella, increased incidence of
      spheromastigotes, agglutination and a novel walnut-like appearance. The reduced
      supply of UDP-galactose was manifest in the two clones as a six- or nine-fold
      reduction in the expression of galactopyranose-containing cell surface mucins and
      negligible or two-fold reduction in the expression of galactofuranose-containing
      glycoinositolphospholipids. The major loss of mucins as opposed to
      glycoinositolphospholipids may indicate that the latter are more important for
      basic parasite survival in culture. The apparent haploid deficiency suggests that
      epimerase levels are close to limiting, at least in the epimastigote form, and
      might be exploited as a potential drug target.

PMID- 16569453
TI  - Global trends in plant transgenic science and technology (1973-2003).
AB  - Transgenic science and technology are fundamental to state-of-the-art plant
      molecular genetics and GM crop improvement. Monitoring the scale and growth of
      this area of science is important to scientists, national and international
      research organizations, funding bodies, policy makers and, because of the GM
      debate, to society as a whole. Literature statistics covering the past 30 years
      reveal a dramatic increase in plant transgenic science in Asia during the past
      decade, a sustained expansion in North America and, recently, a slow down in the
      rest of the world. With the exception of the output of China and India,
      publications focusing on the development of transgenic technology have been
      slowing down, worldwide, since the early mid-1990s, a trend that contrasts with
      the increase in GM crop-related studies.

PMID- 16569454
TI  - RGD motifs on the surface of baculovirus enhance transduction of human lung
      carcinoma cells.
AB  - Baculovirus vectors have been shown to enter a variety of mammalian cell lines
      and gene transfer with wild-type baculovirus (WT) has been demonstrated both in
      vitro and in vivo. Different protein motifs have been displayed on the viral
      surface to serve as ligands for cell-specific receptor molecules. We have
      generated recombinant baculovirus vectors displaying an RGD-motif, recognized by
      alphaV integrin, on the viral surface. The RGD motifs within the C-terminus of
      coxsackie virus A9 and human parechovirus 1 VP1 proteins were fused to the N
      terminus of the major envelope glycoprotein, gp64, of Autographa californica
      multiple nucleopolyhedrovirus. The recombinant RGD-presenting viruses bound more
      efficiently to the surface of human lung carcinoma cells (A549), known to contain
      alphaV integrins, as compared to WT baculovirus. In addition, the binding pattern
      of the RGD-displaying baculovirus showed extensive clustering. This most likely
      represents clustering of the integrin molecules on the cell surface, induced by
      binding of the RGD-displaying baculovirus. Finally, the transduction efficiency
      of an RGD-representing virus increased by almost three-fold as monitored by light
      emission measurements. In conclusion, these results suggest that the RGD-motif is
      functional on the surface of baculovirus and thereby these tropism-modified
      viruses bind more efficiently as well as enhance the transduction efficiency of
      human cancer cells expressing alphaV integrins.

PMID- 16569455
TI  - Improvement of the fungal enzyme pyranose 2-oxidase using protein engineering.
AB  - Native pyranose 2-oxidase (P2Ox) was purified from Peniophora sp. and
      characterized. To improve its catalytic efficiencies and stabilities by protein
      engineering, we cloned and expressed the P2Ox gene in Escherichia coli and
      received active, fully flavinylated recombinant P2OxA. Selenomethionine-labeled
      P2OxA was used for X-ray analysis and the resulting crystal structure enabled the
      rational design using variant P2OxA1 with the substitution E542K as template.
      Besides increased thermal and pH stabilities this variant showed improved
      catalytic efficiencies (k(cat)/K(m)) for the main substrates. A new variant,
      P2OxA2H, with an additional substitution T158A and a C-terminal His(6)-tag
      exhibited significantly decreased apparent K(m) values for D-glucose (0.47 mM), l
      sorbose (1.79 mM), and D-xylose (1.35 mM). Compared to native P2Ox, the catalytic
      efficiencies were substantially improved for D-glucose (230-fold), L-sorbose (874
      fold), and D-xylose (1751-fold). This P2Ox variant was used for the bioconversion
      of L-sorbose under O(2)-saturation in a molar scale. The structure-activity
      relationships of the amino acid substitutions were analyzed by modelling of the
      mutated P2Ox structures. Molecular docking calculations of various carbohydrates
      into the crystal structure of P2OxA and the analysis of the protein-ligand
      interactions in the docked complexes enabled us to explain the substrate
      specificity of the enzyme by a conserved hydrogen bond pattern which is formed
      between the protein and all substrates.

PMID- 16569456
TI  - The xylanolytic enzyme system from the genus Penicillium.
AB  - In nature, there are numerous microorganisms that efficiently degrade xylan, a
      major component of lignocellulose. In particular, filamentous fungi have
      demonstrated a great capability for secreting a wide range of xylanases, being
      the genus Aspergillus and Trichoderma the most extensively studied and reviewed
      among the xylan-producing fungi. However, an important amount of information
      about the production and genetics of xylanases from fungi of the genus
      Penicillium has accumulated in recent years. A great number of Penicillia are
      active producers of xylanolytic enzymes, and the use of xylanases from these
      species has acquired growing importance in biotechnological applications. This
      review summarizes our current knowledge about the properties, genetics,
      expression and biotechnological potential of xylanases from the genus
      Penicillium.

PMID- 16569457
TI  - Community health worker training and certification programs in the United States:
      findings from a national survey.
AB  - OBJECTIVE: To analyze trends and various approaches to professional development
      in selected community health worker (CHW) training and certification programs in
      the United States. We examined the expected outcomes and goals of different
      training and certification programs related to individual CHWs as well as the
      community they serve. METHOD: A national survey of CHW training and certification
      programs. Data collection was performed through personal interviews, phone
      interviews and focus groups. Data sources included public health officials,
      healthcare associations, CHW networks, community colleges, and service providers.
      Initial screening interviews resulted in in-depth interviews with participants in
      19 states. We applied human capital theory concepts to the analysis of the rich
      qualitative data collected in each state. RESULTS: CHW programs in the U.S. seem
      to have been initiated mainly due to lack of access to healthcare services in
      culturally, economically, and geographically isolated communities. Three trends
      in CHW workforce development were identified from the results of the national
      survey: (1) schooling at the community college level - provides career
      advancement opportunities; (2) on-the-job training - improves standards of care,
      CHW income, and retention; and (3) certification at the state level - recognizes
      the work of CHWs, and facilitates Medicaid reimbursement for CHW services.
      CONCLUSION: Study findings present opportunities for CHW knowledge and skill
      improvement approaches that can be targeted at specific individual career,
      service agency, or community level goals. Trained and/or certified community
      health workers are a potential new and skilled healthcare workforce that could
      help improve healthcare access and utilization among underserved populations in
      the United States.

PMID- 16569458
TI  - Do transposable elements really contribute to proteomes?
AB  - Recent studies indicate that the initial classification of transposable elements
      (TEs) as 'useless', 'selfish' or 'junk' pieces of DNA is not an accurate one. TEs
      seem to have complex regulatory functions and contribute to the coding regions of
      many genes. Because this contribution had been documented only at transcript
      level, we searched for evidence that would also support the translation of TE
      cassettes. Our findings suggest that the proportion of proteins with TE-encoded
      fragments (approximately 0.1%), although probably underestimated, is much less
      than what the data at transcript level suggest (approximately 4%). In all cases,
      the TE cassettes are derived from old TEs, consistent with the idea that
      incorporation (exaptation) of TE fragments into functional proteins requires long
      evolutionary periods. We therefore argue that functional proteins are unlikely to
      contain TE cassettes derived from young TEs, the role of which is probably
      limited to regulatory functions.

PMID- 16569459
TI  - Using SAS to conduct nonparametric residual bootstrap multilevel modeling with a
      small number of groups.
AB  - In multilevel modeling, researchers often encounter data with a relatively small
      number of units at the higher levels. As a result, of this and/or non-normality
      of the residuals, model parameter estimates, particularly the variance components
      and standard errors of parameter estimates at the group level, may be biased,
      thus the corresponding statistical inferences may not be trustworthy. This
      problem can be addressed by using bootstrap methods to estimate the standard
      errors of the parameter estimates for significance testing. This study
      illustrates how to use statistical analysis system (SAS) to conduct nonparametric
      residual bootstrap multilevel modeling. Specific SAS programs for such modeling
      are provided.

PMID- 16569460
TI  - Prognosis of patients with resected non-small cell lung cancer: impact of
      clinical and pathologic variables.
AB  - The objective of this study was to determine whether AJCC staging, supplemented
      by additional clinical and pathologic variables could identify a subpopulation of
      pathologically staged NSCLC patients who had been resected for cure with a low
      risk (<20%) of 5-year disease specific mortality. The Surveillance, Epidemiology,
      and End Results (SEER) registry was analyzed to identify and evaluate the disease
      specific 5-year mortality of 17,130 patients with resected and pathologically
      defined Stage I-IIIA disease initially diagnosed from 1988 to 1997. The analyses
      showed that American Joint Commission on Cancer (AJCC) T and N defined stage
      Stage I-IIIA subgroups had approximately a 30, 60, and 75% 5-year disease
      specific mortality, respectively. The 5,366 Stage IA patients were identified as
      having a 5-year disease specific mortality of 25%. Further multivariate analyses
      of Stage IA cases showed predictors of favorable outcome to be tumor size (< 10
      mm), histologic grade (well differentiated), and histologic subtype
      (bronchoalveolar cell). Subgroups identified with two or all three of these
      additional features had an approximately 10% 5-year lung cancer specific
      mortality. Although nearly all patient subgroups with Stages I-IIIA resected and
      pathologically staged NSCLC have substantial (>20%) risk of death from their
      cancer within 5 years of diagnosis, for Stage IA patients additional information
      (tumor size, histologic grade, and histologic subtype) allows additional
      refinement in prognostic estimates and identification of some low risk subgroups.

PMID- 16569461
TI  - Matrix metalloproteinase-13 expression is associated with bone marrow
      microinvolvement and prognosis in non-small cell lung cancer.
AB  - Our previous study demonstrated that bone marrow microinvolvement (BMM) is an
      epiphenomenon of tumor progression rather than a prognostic factor in non-small
      cell lung cancer. We hypothesize that an increase in mesenchymal transition power
      in epithelial tumor cells by up-regulation of the matrix metalloproteinases
      (MMPs) may contribute to the existence of BMM and poorer prognosis. Hereby we
      conducted a prospective study of BMM and MMPs expression in a cohort of 57 non
      small cell lung cancer patients. Bone aspirates were examined by
      immunohistochemical stains. Expressions of MMPs were checked by Human MMP primer
      set kit (Maxim Biotech, USA). Correlations between the MMPs expression and BMM,
      nodal metastasis, and prognosis were examined. Cox model analysis was used to
      identify independent prognostic factors. Though positive BMM was identified in 38
      (66.7%) of the patients, none of the clinicopathological factors, including sex,
      age, cell types, tumor differentiation, nodal metastasis and TNM status of the
      tumor, was related to BMM by the tumor cells. Up-regulation was observed in a
      broad spectrum of MMPs with the exception of MMP-3. However, only MMP-13
      expression correlated with the existence of BMM (p=0.006). Univariate analysis
      revealed MMP-3, MMP-7 and MMP-13 as negative prognostic factors. Cox model
      analysis revealed T-status, cell differentiation, and MMP-13 expression of the
      tumor as independent prognostic factors. The overall 5-year survival rate of the
      patients was 36.8%. The existence of BMM itself did not influence the prognosis
      (p=0.109), however, patients with positive MMP-13 expression (N=34) had a poorer
      5-year survival rate of 26.5% (p=0.025). In summary, non-small cell lung cancer
      cells with MMP-13 expression, despite of BMM status, tend to shed and aggregate
      in the bone marrow, which is subsequently reflected in a poorer survival rate.

PMID- 16569463
TI  - Aluminum resistance of cowpea as affected by phosphorus-deficiency stress.
AB  - Plants growing in acid soils suffer both phosphorus (P) deficiency and aluminum
      (Al) toxicity stresses. Selection of genotypes for adaptation to either P
      deficiency or Al toxicity has sometimes been unsuccessful because these two soil
      factors often interact. Two experiments were conducted to evaluate eight cowpea
      genotypes for Al resistance and to study the combined effect of P deficiency and
      Al toxicity stress on growth, P uptake, and organic acid anion exudation of two
      genotypes of contrasting Al resistance selected from the first experiment.
      Relative root inhibition by 30 microM Al ranged from 14% to 60% and differed
      significantly among the genotypes. Al significantly induced callose formation,
      particularly in Al-sensitive genotypes. P accumulation was significantly reduced
      (28% and 95%) by Al application for both the Al-resistant and the Al-sensitive
      genotypes. Al supply significantly enhanced malate release of root apices of both
      genotypes. However, the exudation rate was significantly higher in the Al
      resistant genotype. P deprivation induced an enhanced malate exudation in the
      presence of Al only in the Al-resistant genotype IT89KD-391. Citrate exudation
      rate of the root apices was lower than malate exudation by a factor of about 10,
      and was primarily enhanced by P deficiency in both genotypes. Al treatment
      further enhanced citrate exudation in P-sufficient, but not in P-deficient
      plants. The level of citrate exudation was consistently higher in the Al
      resistant genotype IT89KD-391 particularly in presence of Al. It is concluded
      that the Al-resistant genotype is better adapted to acid Al-toxic and P-deficient
      soils than the Al-sensitive genotype since both malate and citrate exudation were
      more enhanced by combined Al and P-deficiency stresses.

PMID- 16569462
TI  - Cisplatin and gemcitabine first-line chemotherapy followed by maintenance
      gemcitabine or best supportive care in advanced non-small cell lung cancer: a
      phase III trial.
AB  - PURPOSE: The primary objective of this randomized phase III study was to show
      significant difference in median time to progression (TTP) in patients with
      advanced NSCLC treated with single-agent gemcitabine maintenance therapy versus
      best supportive care following gemcitabine plus cisplatin initial first-line
      therapy. PATIENTS AND METHODS: Chemonaive patients with stage IIIB/IV NSCLC
      received gemcitabine 1,250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day
      1) every 21 days. Patients achieving objective response or disease stabilization
      following initial gemcitabine plus cisplatin therapy were randomized (2:1
      fashion) to receive maintenance gemcitabine (1,250 mg/m(2) on days 1 and 8 every
      21 days) plus best supportive care (GEM arm), or best supportive care only (BSC
      arm). RESULTS: Between November 1999 and November 2002, we enrolled 352 patients
      (median age: 57 years; stage IV disease: 74%; Karnofsky performance status (KPS)
      >80: 41%). Following initial therapy, 206 patients were randomized and treated
      with gemcitabine (138) or best supportive care (68). TTP throughout the study
      period was 6.6 and 5 months for GEM and BSC arms, respectively, while values for
      the maintenance period were 3.6 and 2.0 months (for p < 0.001 for both). Median
      overall survival (OS) throughout study was 13.0 months for GEM and 11.0 months
      for BSC arms (p = 0.195). The toxicity profile was mild, with neutropenia being
      most common grade 3/4 toxicities. CONCLUSION: Maintenance therapy with
      gemcitabine, following initial therapy with gemcitabine plus cisplatin, was
      feasible, and produced significantly longer TTP compared to best supportive care
      alone. Further studies are warranted to establish the place of maintenance
      chemotherapy in patients with advanced NSCLC.

PMID- 16569464
TI  - Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in
      Alzheimer disease.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and insulin-like growth factor-I (IGF-I)
      have been involved in the pathogenesis of Alzheimer's disease (AD) as neurotoxic
      and survival factors, respectively. Recent experimental studies suggest that the
      signalling pathways of TNF-alpha and IGF-I are functionally interrelated. In
      order to investigate the possible interaction of TNF-alpha and IGF-I in AD and
      mild cognitive impairment (MCI), the serum levels of total IGF-I, free IGF-I and
      TNF-alpha were determined in 141 AD patients, 56 MCI cases and 30 controls. As
      compared with controls, AD patients showed increased TNF-alpha and decreased IGF
      I levels in serum, as well as a significant negative correlation between TNF
      alpha and free IGF-I values. MCI patients also exhibited significantly higher TNF
      alpha levels than controls. The present results suggest that increased TNF-alpha
      levels are involved in the pathogenesis of AD and MCI, and might antagonize the
      neurotrophic activity of IGF-I in these medical conditions. In addition, the
      combined determination of TNF-alpha and IGF-I might be useful to monitor anti
      inflammatory and/or neurotrophic drug effects in AD.

PMID- 16569465
TI  - Differential gene expression profiles in the hippocampus of senescence
      accelerated mouse.
AB  - The senescence-accelerated mouse (SAM) is an animal model for studying senescence
      and age-associated disorders due to its inherited aging phenotype. The SAM/prone8
      (SAMP8) is a useful animal model to investigate the fundamental mechanisms
      involved in age-related learning and memory deficits that may have relevance to
      age-associated AD, while SAM/resistant1 (SAMR1) shows normal. To identify genes
      rendering the cognitive deterioration with aging, the subtractive cDNA libraries
      containing 1924 clones with the positive ratio of 96.18% were generated and the
      microarray containing 3136 cDNA was prepared. The results of screening libraries
      by the microarray showed that of all 91 differentially expressed genes, 50 were
      over-expressed and 41 were low-expressed in SAMP8. Some of the identified genes
      were confirmed by the real time quantitative RT-PCR. These results indicated the
      profiles of gene expression in the hippocampus of SAMP8 and SAMR1 were
      significantly different, which may play important roles in the age-related
      cognitive deficit in SAMP8, suggesting those genes related to the cognitive
      deficient or pathology change in the brain of SAMP8 may be potential gene targets
      for Alzheimer's disease therapy.

PMID- 16569466
TI  - MR features of the substantia innominata and therapeutic implications in
      dementias.
AB  - We measured the thickness of the substantia innominata using magnetic resonance
      imaging in 122 patients with Alzheimer's disease (AD), 31 patients with dementia
      with Lewy bodies (DLB) and 34 patients with vascular dementia (VaD), and examined
      the correlates of cognitive response to donepezil. Although all dementia groups
      showed significant atrophy of the substantia innominata compared to 28 age
      matched controls, atrophy was greater in the DLB group, but less in the VaD group
      than the AD group. Mini-Mental State Examination score changes at 12 weeks after
      donepezil administration inversely and significantly correlated with the
      thickness of the substantia innominata in patients with AD (n=103, r=-0.43,
      p<0.0001) and in patients with DLB (n=24, r=-0.57, p<0.01), but not in patients
      with VaD (n=12, r=-0.22, p>0.1). There may be some differences in cholinergic
      impairment among AD, DLB and VaD, reflecting cholinergic neuropathology. Clinical
      response to cholinergic therapy may be partly attributable to damaged cholinergic
      neurons in AD and DLB, but not in VaD, suggesting differences in the therapeutic
      implication of cholinergic system degeneration.

PMID- 16569467
TI  - Timeliness of childhood immunisation in Australia.
AB  - There are few data, especially outside the United States, examining the
      timeliness of childhood vaccination, although it is of key importance for
      diseases such as pertussis, and invasive disease due to Haemophilus influenzae
      type b and Streptococcus pneumoniae. The aim of this study was to use the unique
      resource of the Australian Childhood Immunisation Register (ACIR) to examine
      trends in and factors associated with timeliness of infant vaccination at the
      national level. As in previous studies, age-appropriate immunisation was defined
      as within 30 days of the recommended age. Vaccination delays became more common
      for later doses, given at an older age, but long delay (greater than 6 months)
      occurred in only 1-2%. Although immunisation coverage increased over time,
      timeliness did not improve. Among Indigenous infants, long delays occurred in 5
      12% of those residing in very remote areas, but by 2 years of age, overall
      immunisation coverage was similar to non-Indigenous children. With immunisation
      coverage at the key indicator ages of 12 and 24 months now high in most
      industrialised countries including Australia, timeliness of vaccine doses should
      be the next benchmark to aim for in program performance, especially in specific
      sub-groups such as Indigenous children who stand to gain most from prevention of
      early onset disease.

PMID- 16569468
TI  - A comprehensive patient assessment and physician reminder tool for adult
      immunization: effect on vaccine administration.
AB  - We determined if a patient-self assessment/provider reminder tool (A/R) would
      increase administration of the eight vaccines that may be indicated for adults.
      In three family practice clinics, the A/R was completed by intervention patients
      and given to their provider. Control patients received an exercise reminder. On
      the day of the intervention, influenza, pneumococcal polysaccharide, and tetanus
      diphtheria (Td) vaccines vaccine were administered significantly (P<0.01) more
      commonly to intervention patients in one clinic, Td in the second, and none in
      the third. There were no additional significant differences during one year of
      follow-up. A number of barriers to comprehensive vaccination were encountered.

PMID- 16569469
TI  - Quantifying the contribution of nitrification and denitrification to the nitrous
      oxide flux using 15N tracers.
AB  - Microbial transformations of nitrification and denitrification are the main
      sources of nitrous oxide (N2O) from soils. Relative contributions of both
      processes to N2O emissions were estimated on an agricultural soil using 15N
      isotope tracers (15NH4+ or 15NO3-), for a 10-day batch experiment. Under
      unsaturated and saturated conditions, both processes were significantly involved
      in N2O production. Under unsaturated conditions, 60% of N-N2O came from
      nitrification, while denitrification contributed around 85-90% under saturated
      conditions. Estimated nitrification rates were not significantly different
      whatever the soil moisture content, whereas the proportion of nitrified N emitted
      as N2O changed from 0.13 to 2.32%. In coherence with previous studies, we
      interpreted this high value as resulting from the decrease in O2 availability
      through the increase in soil moisture content. It thus appears that, under
      limiting aeration conditions, some values for N2O emissions through nitrification
      could be underestimated.

PMID- 16569470
TI  - Making sense of eating, weight and risk in the early teenage years: views and
      concerns of parents in poorer socio-economic circumstances.
AB  - This paper reports findings from a qualitative study which examined the
      perceptions and understandings underpinning the dietary practices in families
      with 'normal' weight and 'overweight' young teenagers living in poorer socio
      economic circumstances. Thirty four parents/main food providers of boys and girls
      aged 13-14 years from socio-economically disadvantaged areas in Eastern Scotland
      were interviewed. Within the home there was a strong acknowledgement of these
      early teenagers' own food preferences; parents also saw them as having increasing
      responsibility for their own food choices outwith the home but these were often
      described as 'not healthy' choices. However, parents saw dietary issues as of
      fairly low priority in the hierarchy of health-relevant and other risks facing
      their teenagers. Equally, these interviewees felt that issues around body shape
      and size at this age were less potentially problematic than the risks to
      teenagers' mental or physical health of their becoming obsessed with weight loss.
      Parents often made sense of their teenager's body size and shape in terms of the
      variety of body types in families and inherited traits. Interviewees seemed to
      lack a discourse to understand weight and overweight in this age group, falling
      back on understandings derived from the adult lifestage.

PMID- 16569471
TI  - Developmental reflexes and 31P Magnetic Resonance Spectroscopy of basal ganglia
      in antipsychotic-naive schizophrenia.
AB  - The study examined the high energy-phosphate metabolism of basal ganglia in
      antipsychotic-naive schizophrenia patients with and without developmental
      reflexes in comparison to healthy subjects. Nineteen antipsychotic-naive
      schizophrenics of whom 11 had developmental reflexes and 26 age-sex-matched
      healthy subjects without developmental reflexes underwent in-vivo 2-D 31P
      Magnetic Resonance Spectroscopy of basal ganglia on a 1.5-T scanner. Mean age-at
      onset of psychosis was significantly lower in patients with developmental
      reflexes. Mean PCr/Total ATP ratio in bilateral basal ganglia was lower in
      patients than healthy subjects. The ratio was the least in patients with
      developmental reflexes (F=10.7; df=2, 42; p<0.001). Schizophrenia patients with
      developmental reflexes had the lowest PCr/Total ATP ratio in basal ganglia
      indicating more severe metabolic abnormality. These patients had younger age-at
      onset of psychosis. Together, this suggests neurodevelopmental etiopathogenesis
      in schizophrenia.

PMID- 16569473
TI  - The bleaching of teeth: a review of the literature.
AB  - OBJECTIVES: To review current knowledge of tooth whitening with respect to
      external bleaching methods. DATA: The scope is the external bleaching of vital
      teeth and focuses on mechanisms; in vivo and in vitro measurement methods, and
      factors influencing the efficacy of the whitening process. SOURCES: "Medline" and
      "ISI Web of Science" databases from 1966 and 1974, respectively were searched
      electronically with key words tooth, teeth, colo*r, white*, bleach* and peroxide.
      CONCLUSIONS: The importance of tooth whitening for patients and consumers has
      seen a dramatic increase in the number of products and procedures over recent
      years, with a concomitant rise in publications on this topic. Literature suggests
      that the mechanisms of tooth whitening by peroxide occur by the diffusion of
      peroxide through enamel to cause oxidation and hence lightening of coloured
      species, particularly within the dentinal regions. A number of approaches are
      available for measuring changes in tooth colour. These include visual
      measurements by trained clinicians and instrumental measurements using
      spectrophotometry, chromameters and digital image analysis. The key factors that
      affect tooth whitening efficacy by peroxide containing products are concentration
      and time. In general, higher concentrations are faster than lower concentrations.
      However, lower concentrations can approach the efficacy of higher concentrations
      with extended treatment times. Alternative bleach systems to peroxide have
      received only minor attention. The efficacy of light activated systems versus non
      light activated controls in clinical studies is limited and conflicting. Other
      factors which can influence tooth bleaching outcome include type of stain,
      initial tooth colour and subject age.

PMID- 16569474
TI  - A novel system for environmental monitoring through a cooperative/synergistic
      scheme between bioindicators and biosensors.
AB  - This paper addresses environmental monitoring through a robust dynamic
      integration between biomonitor and biosensor systems, a strategy that has not
      been attempted before. The two systems are conceptually interrelated and
      methodologically correlated to a cooperative/synergistic scheme (CSS) with a view
      to minimise uncertainty and monitoring costs and increase reliability of
      pollution control and abatement. The structures and operations of the biosensor
      component (in terms of sensitivity, device and method versatility, nature
      mimicking physicochemical mechanisms, prospects and technological input) are such
      that they reinforce or promote the structures and operations of the natural
      component (in terms of bio-surveillance, impact assessment, environmental quality
      indexing, stress responses, metabolic pathways, etc.) and vice versa. The
      bioindicator ontology presented herein, including concepts, relations and
      controlled vocabulary aiming at establishing an integrated methodology for
      mapping/assessing negative environmental externalities, provides a useful tool
      for the design/development/implementation of an environmental network for the
      monitoring of a variety of pollutants over time and space and the assessment of
      environmental quality; the collection of the available information and its
      classification into taxonomic and partonomic relations allows the construction of
      a database that links pollutants with organisms' response, at a phenomenological
      and in-depth level, considering ecological parameters, relations and
      geomorphologic characteristics. As a result, a computer program has been
      designed/developed as a decision support system and has been successfully tested
      on a representative population of species indigenous to southern Greece.
      Significantly, a novel system in the form of a rational framework at the
      conceptual design level has been developed, that actually contributes towards
      achieving a cost-effective long-term monitoring program, with the flexibility to
      counter on-course any (anticipated or not) variations/modifications of the
      surveillance environment. This novel and pioneering approach will further offer a
      dynamic system utilised in (a) environmental impact studies and risk assessment
      (positive/analytic approach), (b) decision-making in the short-run
      (normative/tactic approach), and (c) policy-making in the long-run
      (normative/strategic approach). The proposed CSS, based on the integration of
      multiple data sources, can establish a local area network, incorporated
      into/expanding to a wide area network, thus offering the potential of better
      predictive ability and greater lead-time warning at alarm conditions than that
      provided by separate, stand-alone surveillance modalities.

PMID- 16569475
TI  - Expression of functional aromatase in the epididymis: role of androgens and LH in
      modulation of expression and activity.
AB  - The primary source of 17beta-estradiol (E2) in the male is the testis, which
      expresses the enzyme complex aromatase that is involved in E2 biosynthesis.
      However, recent evidences suggest that the epididymis is also capable of E2
      biosynthesis. Our results demonstrate the presence of cytochrome P450 aromatase
      (P450(AROM)) and 17beta-hydroxysteroid dehydrogenase I messenger ribonucleic acid
      (mRNA) in the caput and cauda regions of rat epididymis. The androgenic
      substrates testosterone and androstenedione could be utilized by the rat
      epididymal aromatase for E2 biosynthesis as assessed by radioimmunoassay.
      P450(AROM) expression is transcriptionally regulated in a tissue-specific manner
      by various factors including androgens and luteinizing hormone (LH). Androgens
      could positively modulate epididymal P450(AROM) mRNA levels as assessed by
      castration studies, treatment with flutamide or in vitro incubation of tissue
      minces with 5 alpha-dihydrotestosterone (DHT). Several extra-gonadal tissues
      including the epididymis are known to express LH receptors (LHR). Our study
      revealed a higher level of LHR mRNA expression in the cauda region compared to
      the caput. Caudal membrane extracts could bind human chorionic gonadotropin
      (hCG), which resulted in the production of cAMP. Interestingly, hCG could also
      regulate P450(AROM) mRNA expression in vitro and enhance E2 biosynthesis.
      Together our results highlight the presence of a functional aromatase in the
      epididymis that is subject to regulation by LH and androgens.

PMID- 16569476
TI  - Functional switch of viral protein HBx on cell apoptosis, transformation, and
      tumorigenesis in association with oncoprotein Ras.
AB  - The X protein (HBx) of hepatitis B virus (HBV) plays important roles in
      hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) during viral infection.
      In this study, we demonstrated that co-transfection of mouse embryo fibroblasts
      (STO) with HBx and activated Ras triggered apoptotic cell death, while HBx or
      activated Ras individually failed to induce apoptosis. In addition, STO cells
      were able to form colonies on soft agar after transfected with HBx or Ras, and
      cells co-transfected with both genes failed to transform. Moreover, nude mice
      injected with STO cells carrying either HBx or Ras could develop tumor, but tumor
      growth was inhibited by the injection of both STO cells harboring HBx and
      carrying Ras. These results suggested that HBx plays a role as a tumor inducer
      and stimulates neoplastic transformation of normal cells, but shifts its function
      to the induction of apoptosis in association with Ras.

PMID- 16569477
TI  - Effects of arsenic trioxide on the cellular proliferation, apoptosis and
      differentiation of human neuroblastoma cells.
AB  - A human neuroblastoma cell line, IMR-32, was used as an in vitro model system to
      study the effects of arsenic trioxide (As(2)O(3)) on aggressive human
      neuroblastoma. From 0.5 micro M, As(2)O(3) exhibited a dose-dependent inhibition
      of IMR-32 proliferation. At concentrations of 1.5 micro M or higher, As(2)O(3) up
      regulated caspase 3, leading to cellular apoptosis. However, neurofilament-200
      kDa and tyrosine hydroxylase were not up-regulated, implying minimal neuronal
      differentiation. Concomitantly, TrkA was down-regulated and TrkB up-regulated.
      Pre-treatment with the protein kinase C (PKC) inhibitor Ro-31-8220 partially
      blocked As(2)O(3)-mediated apoptosis, meaning that As(2)O(3) might signal through
      PKC activation. The results suggest that As(2)O(3) might be potentially useful in
      neuroblastoma.

PMID- 16569479
TI  - Real-time telomerase assay of less-invasively collected esophageal cell samples.
AB  - Genomic and proteomic efforts have discovered a complex list of biomarkers that
      identify human disease, stratify risk of disease within populations, and monitor
      drug or therapy responses for treatment. Attention is needed to characterize
      these biomarkers and to develop high-throughput technologies to evaluate their
      accuracy and precision. Telomerase activity is correlated with tumor progression,
      indicating cells that express telomerase possess aggressive clinical behavior and
      that telomerase activity could be a clinically important cancer biomarker.
      Traditionally, the detection of cancer has involved invasive procedures to
      procure samples. There is a need for less invasive approaches suitable for
      population- and clinic-based assays for cancer early detection. Esophageal
      balloon cytology (EBC) is a low-invasive screening technique, which samples
      superficial epithelial cells from the esophagus. Since telomerase activity is
      absent in superficial cells of normal esophageal squamous epithelium but is often
      present in superficial cells from dysplastic lesions and ESCCs, measuring
      telomerase activity in EBC samples may be a good way to screen for these lesions.
      The development of rapid real-time telomerase activity assays raises the
      possibility of extending such screening to high-risk populations. In this study,
      we evaluate the feasibility of using rapid Real-Time Telomerase Repeat
      Amplification Protocol (RTTRAP) for the analysis of NIST telomerase candidate
      reference material and esophageal clinical samples. The telomerase activity of
      eight EBC samples was also measured by capillary electrophoresis of RTTRAP
      products, RApidTRAP, and hTERT mRNA RT-PCR assays. These findings demonstrate the
      feasibility of using the RTTRAP assay in EBC samples and suggest that individuals
      from high-risk populations can be screened for telomerase activity.

PMID- 16569478
TI  - High sensitivity of fatty liver Shionogi (FLS) mice to diethylnitrosamine
      hepatocarcinogenesis: comparison to C3H and C57 mice.
AB  - The fatty liver Shionogi (FLS) mouse is a new inbred strain that spontaneously
      develops fatty liver with infiltration of mononuclear cells. Moreover, this mouse
      is known to frequently develop spontaneous hepatic cancers. Recently, human non
      alcholic steatohepatitis (NASH) has been focused of attention regarding
      hepatocellular carcinoma. Therefore, this mouse has potential as a model for
      human hepatic cancer due to steatosis. It is of interest therefore, whether it
      exhibits elevated susceptibility not only regarding spontaneous tumor development
      but also to chemical hepatocarcinogens. To examine this concern, we examined
      diethylnitrosamine (DEN) hepatocarcinogenesis in FLS mice with 30ppm in drinking
      water for 26 weeks in comparison to two other strains of mice, C3H and C57. The
      induction of spontaneous and DEN-induced hepatic tumors was clearly increased in
      the FLS case, along with levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker
      of oxidative DNA damage, as compared to the other strains, with or without DEN
      treatment. These results indicate that the oxidative DNA stress is intimately
      involved in hepatocarcinogenesis in FLS mice and provide further support for use
      of this mouse as a useful model for investigating hepatocarcinogenesis due to
      human hepatic steatosis.

PMID- 16569480
TI  - Case-control study of vascular endothelial growth factor (VEGF) genetic
      variability in Alzheimer's disease.
AB  - Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis
      and blood vessel function. Recent evidence indicates that VEGF facilitates memory
      and learning through stimulating angiogenesis and neurogenesis in the rat
      hippocampal dendate gyrus. Abnormal regulation of VEGF expression has been
      reported in the pathogenesis of both atherosclerosis and motoneuron degeneration
      in amyotrophic lateral sclerosis, with low VEGF-producing polymorphisms (-2578
      allele A and -634 allele G) conferring increased susceptibility for the
      development of the disorders. We tested whether these polymorphisms
      downregulating expression of VEGF might increase the risk of developing
      Alzheimer's disease (AD). So, we performed a case-control study in 362 Spanish AD
      patients and 428 healthy controls. The current study does not demonstrate an
      association between VEGF (-2578) and VEGF (-634) genotypes or haplotypes and AD.

PMID- 16569481
TI  - The effect of asymmetry of posture on anticipatory postural adjustments.
AB  - The study investigates the effect of body asymmetry on anticipatory postural
      adjustments (APAs). Subjects performed a task involving a standard load release
      induced by a shoulder abduction movement while standing symmetrically or in an
      asymmetrical stance with either their right or left leg in 45 degrees of external
      rotation. EMG activities of trunk and leg muscles were recorded during the
      postural perturbation and were quantified within the time intervals typical of
      APAs. Anticipatory postural adjustments were observed in all experimental
      conditions. It was found that asymmetrical body positioning was associated with
      significant asymmetrical patterns of APAs seen in the right and left distal
      muscles. These APA asymmetries were dependant upon the side in which the body
      asymmetry was induced: reduced APAs were observed in the leg muscles on the side
      of leg rotation, while increased APAs were seen in the muscles on the
      contralateral side. These findings stress the important role that body
      asymmetries play in the control of upright posture.

PMID- 16569483
TI  - Nomenclature for parasitic diseases: cohabitation with inconsistency for how long
      and why?
AB  - The author surveys the early history of nomenclature for parasitic diseases or
      infections which led to the existing usage of synonymous names with diverse
      spellings for denominating the same disease entities. In order to diminish
      heterogeneity in nomenclatural usage, principles of the standardized nomenclature
      of parasitic diseases (SNOPAD) have been put forward by the World Association for
      the Advancement of Veterinary Parasitology. Pros and cons regarding the SNOPAD
      concept are discussed in seeking consensus terminology. The need for a standard
      nomenclature may be judged differently. SNOPAD is just a guideline based on
      carefully reasoned and clearly defined principles for those authors and editors
      dissatisfied with the existing heterogeneous and inconsistent nomenclatural usage
      and wish to rely on a uniform and standard disease nomenclature. The major
      suggestion of SNOPAD is the use solely of suffix -osis when disease name is
      coined from the name of a parasite taxon. Meanwhile, the proposed principles were
      found sensible and accepted more in the field of veterinary, less in medical
      parasitology. In a recent survey it has been revealed that the majority (73.8%)
      of 126 national language parasitological textbooks or compendia from 21 countries
      of Europe published since 1990 adopted consistent '-osis' disease terminology and
      the rest (26.2%) used a mixture of disease names ending in '-osis' and '-iasis'
      inconsistently. For achieving substantial shift towards the use of more
      consistent disease terminology, the interest and support of the parasitologists'
      community is required. Editorials and database producers hold the key to further
      progress provided they see the advantages of the use of a single name of
      worldwide currency for each disease entity.

PMID- 16569482
TI  - Kinetics of energy source utilization in Boophilus microplus (Canestrini, 1887)
      (Acari: Ixodidae) embryonic development.
AB  - The present work evaluates the kinetics of utilization of the main potential
      energy sources throughout the embryonic developmental stages of Boophilus
      microplus. The embryonic development of this arthropod is completed in 21 days.
      Cellularization of the blastoderm occurs on the 6th day and is rapidly followed
      by germ band extension and segmentation, whose first signs are visible on the 7th
      day. Cellularization is typically a maternal-driven process, carried out by
      molecular determinants deposited in the oocyte during oogenesis. On the other
      hand, segmentation is of zygotic nature, being the consequence of the synthesis
      of various components by the growing embryo. The enhancement in total B.
      microplus RNA was observed after cellularization, corroborating the replacement
      of maternal-driven processes by embryonic zygotic expression. An abrupt increase
      in oxygen consumption was observed from cellularization until the 8th day of
      development. The reduction in dry weight at the same period and the
      susceptibility of oxygen consumption to KCN suggest that the respiration process
      is activated during early embryonic development. A marked decrease in total lipid
      content occurred between the 5th and 7th days of development, suggesting this is
      the main energy source for cellularization. A major reduction in carbohydrate
      content occurred later, between the 7th and 9th days, and it could be assigned to
      the morphological segmentation of the embryo. Although the total amount of
      proteins remains unchanged from oviposition to hatching, a 15% reduction in
      vitellin (VT) content was observed before cellularization, up to the 4th day
      after egglaying. This observation was correlated to the synthesis of new proteins
      needed to support early embryo development. Additional 20% of VT was consumed
      thereafter, mainly at the end of embryogenesis, and in this case VT is probably
      used as energy source to the older embryo. Altogether, these data indicate
      different energy sources for maternal and zygotic driven processes.

PMID- 16569485
TI  - Supercritical fluid assisted impregnation of indomethacin into chitosan
      thermosets for controlled release applications.
AB  - Supercritical carbon dioxide (sc-CO(2)) was used to impregnate indomethacin (a
      non-steroidal anti-inflammatory drug) into chitosan thermosets for the
      preparation of controlled release formulations. The products were analyzed by a
      range of methods including powder X-ray diffraction (XRD) and scanning electron
      microscopy (SEM). The effects of the experimental temperature and pressure of the
      sc-CO(2) on the thermal behavior of chitosan-indomethacin drug composites (DCs)
      was investigated via differential scanning calorimeter (DSC). The interaction of
      chitosan and indomethacin after impregnation was then studied by Fourier
      transform infrared (FTIR) and Raman spectroscopy, respectively. Our results
      suggest that the supercritical fluid impregnation process results in indomethacin
      being amorphously dispersed within the chitosan matrix. FTIR data suggest that
      the aliphatic carbonyl group of indomethacin interacts with the NH(2) group of
      the chitosan backbone. In vitro dissolution studies (via UV-vis spectroscopy)
      reveal that the dissolution rate of indomethacin substantially increases after
      processing in sc-CO(2), particularly, under the experimental conditions 20.7 MPa
      and 70 degrees C.

PMID- 16569484
TI  - High inter-individual variation in the gestation length of the hedgehog tenrec,
      Echinops telfairi (Afrotheria).
AB  - The gestation length (GL) of Tenrecs (Tenrecinae, Afrotheria) is still uncertain.
      This lack of knowledge also applies to the lesser hedgehog tenrec, Echinops
      telfairi, the species most commonly bred and maintained in captivity. The animals
      used in this study were held under controlled conditions (light, temperature and
      humidity). In order to determine the GL, groups of female tenrecs were subjected
      to various mating procedures followed by isolation periods of different lengths.
      A total of n=249 pregnancies were analysed and the number of offspring per litter
      was 3.29+/-0.09. The length of gestation could be determined in n=199 pregnancies
      and a mean GL of 67.53+/-0.36 days was calculated. Initial attempts with
      isolation periods of less than 16 days did not allow to accurately define the GL.
      Experiments with longer isolation periods and females subjected to only one
      mating procedure (n=10) revealed a variation in the GLs of 57-79 days. However,
      in one female a GL of only 50 days was also observed indicating an even greater
      range in GL variation. There was a statistically significant tendency for shorter
      GLs in the animals that conceived later in the mating season, but no statistical
      evidence was found that age, parity or litter size played an essential role in
      determining the GL. In conclusion, an unexpected high variability in gestation
      length in E. telfairi was demonstrated although the study animals were kept under
      controlled environmental conditions. The factors and mechanisms regulating this
      high intra-species variability in gestation length need further investigations.

PMID- 16569486
TI  - Lipidic implants for controlled release of bioactive insulin: effects on
      cartilage engineered in vitro.
AB  - Controlled release systems for growth factors and morphogens are potentially
      powerful tools for the engineering or the treatment of living tissues. However,
      due to possible instabilities of the protein during manufacture, storage, and
      release, in the development of new release systems it is paramount to investigate
      into the maintenance of bioactivity of the protein. Within this study, recently
      developed protein releasing lipid matrix cylinders of 2 mm diameter and 2 mm
      height made from glycerol tripalmitate were manufactured in a compression process
      without further additives. Insulin in different concentrations (0.2%, 1%, and 2%)
      served as model protein. The bioactivity of the protein released from the
      matrices was investigated in a long-term cartilage engineering culture for up to
      four weeks; additionally, the release profiles were determined using ELISA.
      Insulin released from the matrices increased the wet weights of the cartilaginous
      cell-polymer constructs (up to 3.2-fold), the amount of GAG and collagen in the
      constructs (up to 2.4-fold and 3.2-fold, respectively) and the GAG and collagen
      content per cell (1.8-fold and 2.5-fold, respectively), compared to the control.
      The dose-dependent effects on tissue development correlated well with release
      profiles from the matrices with different insulin loading. In conclusion, the
      lipid matrices, preserving the bioactivity of incorporated and released protein,
      are suggested as a suitable carrier system for use in tissue engineering or for
      the localized treatment of tissues with highly potent protein drugs such as used
      in the therapy of brain cancer or neurodegenerative CNS diseases.

PMID- 16569487
TI  - Proapoptotic effect of Uncaria tomentosa extracts.
AB  - Uncaria tomentosa ("Una de gato") (Rubiaceae) is widely used in South America for
      treatment of gastritis, arthritis, cancer and inflammatory conditions. Recent
      literature reports cytostatic, antiproliferative, anti-inflammatory, mutagenic
      and anti-mutagenic properties of extracts of the plant. The present study
      investigates the possible proapoptotic mechanism via the activation of caspase3,
      in cytostatic effects of root bark extracts of Uncaria tomentosa on three
      different tumoral cell lines.

PMID- 16569488
TI  - Analytical characterisation of the routes by thermolytic decarboxylation from
      tryptophan to tryptamine using ketone catalysts, resulting in tetrahydro-beta
      carboline formation.
AB  - N-Alkylated tryptamines have complex psychoactive properties. Routes for
      clandestine synthesis are described on Internet websites one of which involves
      the thermolytic decarboxylation of tryptophan to tryptamine as a precursor to
      psychoactive compounds. High boiling solvents and ketone catalysts have been
      employed to facilitate the decarboxylation of tryptophan. The present study has
      revealed that there is formation of tetrahydro-beta-carboline (THBC) derivatives
      which may originate from reaction with both the solvent and the ketone catalyst.
      The application of gas chromatography electron- and chemical-ionisation ion trap
      tandem mass spectrometry (GC-IT-MS-MS), in combination with nuclear magnetic
      resonance (NMR), led to the isolation and identification of 1,1-disubstituted
      tetrahydro-beta-carbolines formed as major impurities in the tryptamine.
      Confirmation was by synthesis of the THBC derivatives from tryptamine using
      Pictet-Spengler cyclisation. Under EI-conditions, mass spectral characterisation
      of the THBCs suggests predominance of alkyl cleavage. These impurities will yield
      a useful profile for identification of the synthetic pathway and likely reagents
      employed, particularly a "fingerprint" of the ketone catalyst and an insight into
      the influence of solvents and catalysts on the formation of by-products.

PMID- 16569489
TI  - Determination of furosemide in plasma and urine using monolithic silica rod
      liquid chromatography.
AB  - In the present study we developed a fast and reliable HPLC assay for the
      determination of the loop diuretic furosemide in plasma and urine, using a
      Chromolith RP 18e (100 mm x 4.6 mm) monolithic silica rod HPLC column. After
      liquid-liquid extraction with diethylether plasma or urine samples were separated
      with a gradient consisting of solvent A (20% acetonitrile) and solvent B (80%
      acetonitrile), both in 0.25% acetic acid. The flow rate was 3.5 ml/min and the
      effluent was monitored by fluorescence with excitation at 230 nm and emission at
      410 nm. The retention times for the internal standard (naproxen) and for
      furosemide were 2.1 and 3.7 min, respectively, and total run time was 8 min. The
      calibration curves were linear between 7.8 and 1000 ng/ml, and within-assay and
      between-assay coefficients of variation were <6.5% and <10%, respectively. The
      proposed assay for furosemide in plasma and urine using monolithic silica rod
      chromatography is fast, sensitive, and reliable, and, thus, well suited for
      pharmacokinetic studies.

PMID- 16569490
TI  - Adrenomedullin (AM) and adrenomedullin binding protein (AM-BP) in the bovine
      mammary gland and milk: Effects of stage of lactation and experimental
      intramammary E. coli infection.
AB  - Adrenomedullin (AM) has been characterized as an endogenous tissue survival
      factor and modulator of many inflammatory processes. Because of the increased
      susceptibility of the mammary gland to infection during the time surrounding
      parturition in the cow, we investigated how milk and tissue content of AM and its
      binding protein (AM-BP) might be affected by the stage of lactation and the udder
      health status. Milk and mammary biopsy samples were obtained from Holstein cows
      21 days prior to and at various times after calving to represent the dry period
      and early and mid-stages of lactation. Additional cows received an intramammary
      challenge with Escherichia coli for immunohistochemical characterization of AM
      and AM-BP. Milk AM concentrations were relatively constant across the stages of
      lactation while AM-BP increased two-fold (P<0.04) between early and mid
      lactation. Milk AM (P<0.04) and AM-BP (P<0.03) increased as somatic cell counts
      (SCCs) increased within a given stage of lactation. Tissue content of both (AM
      and AM-BP) were significantly affected by stage of lactation, lowest in the dry
      period and progressively increasing to peak at mid-lactation as well as
      increasing in association with higher levels of SCCs. Following E. coli
      challenge, AM increased in epithelial cells surrounding mammary alveoli
      presenting high levels of SCCs. The data suggest that AM and AM-BP are
      cooperatively regulated in the mammary gland during lactation; changes in
      localized tissue AM and AM-BP content reflect a dynamic regulation of these
      tissue factors in the bovine mammary gland consistent with their protective
      effects within inflamed tissue.

PMID- 16569492
TI  - The incidence and significance of micrometastases in lymph nodes of patients with
      ductal carcinoma in situ and T1a carcinoma of the breast.
AB  - AIM: To report the incidence and predictive value of positive axillary nodes in
      ductal carcinoma in situ (DCIS) and T1a carcinoma of the breast. METHODS: Cases
      from The Netherlands Cancer Institute were used to determine the incidence of
      lymph-node metastases. All consecutive patients with primary breast cancer that
      were treated between 1989 and 1998 and who had undergone axillary dissection were
      selected. Patients were identified with pure DCIS (n = 71), DCIS with small
      invasion (n = 12), invasive ductal/lobular carcinoma (IDC/ILC) < or =5 mm (n =
      18) or tubular carcinoma < or =10 mm (n = 17). All archived lymph nodes of these
      patients were re-evaluated using immunohistochemistry (IHC). RESULTS: In DCIS the
      incidence increased from 1.4% with routine staining to 11% with IHC. For DCIS
      with small invasion it was 0 vs 27%, respectively. In IDC/ILC sized 2-5 mm the
      incidence rose from 6 to 12% and in tubular carcinoma < or =10 mm from 0 to 12%.
      All but one of the immunohistochemically detected metastases were isolated tumour
      cells (n = 9) or small (micro)metastases (n = 4). Maximally two nodes per patient
      were affected. None of the patients with positive lymph nodes died during follow
      up (mean 102 months). CONCLUSIONS: Survival of our patients appeared not to be
      influenced by the finding of micrometastases in the lymph nodes by IHC.
      Immunohistochemistry of the sentinel node seems not contributive to further
      treatment in these patients.

PMID- 16569493
TI  - Intraoperative evaluation of axillary sentinel lymph nodes using touch imprint
      cytology and immunohistochemistry. Part II. Results.
AB  - AIM: In order to operate selectively on positive axillae during the initial
      operative session for early breast cancer, an accurate and rapid intraoperative
      method to examine an axillary node sample (ANS) or a sentinel node biopsy (SNB)
      is required. The aim of this study was to determine the feasibility and accuracy
      of Immunohistochemistry (IHC)-stained touch imprints in detecting metastatic
      axillary nodes intraoperatively. MATERIAL AND METHODS: Four hundred and thirty
      two axillary nodes from 52 patients (23 axillary node clearance (ANC), 15 ANS and
      14 SNB) were bisected, imprinted and stained with anti-cytokeratin 19 IHC.
      Results were compared with those of routine haematoxylin and eosin (H&E)-stained
      sections. RESULTS: IHC imprints detected 32 positive nodes from 12 patients. H&E
      sections detected 31 positive nodes from 11 patients. IHC imprints missed
      metastases in three nodes and missed the diagnosis of positive axillae in two
      patients. H&E missed metastases in four nodes and missed the diagnosis of
      positive axillae in 3 patients. On a node-basis, sensitivities were 91.4 and
      88.5%, negative predictive values (NPV) were 99.2 and 99.0% and overall
      accuracies were 99.3 and 99.1% for IHC imprints and H&E sections, respectively.
      On a patient-basis, sensitivities were 85.7 and 78.5%, NPVs were 95.2 and 93.1%
      and overall accuracies were 96.1 and 94.2% for IHC imprints and H&E sections
      respectively. There were no false positives. Interpretation of the results by a
      non-histopathologist was concordant with that of a histopathologist. Results
      might be obtained within 30-45 min depending on the number of examined nodes.
      CONCLUSION: Intraoperative IHC staining of touch imprints of axillary sentinel
      nodes is feasible and is a reliable method for evaluating axillary nodes. Slides
      can be reliably interpreted by a trained non-histopathologist.

PMID- 16569491
TI  - The interval from surgery to chemotherapy in the treatment of advanced epithelial
      ovarian carcinoma.
AB  - BACKGROUND: To study the effect of the interval between surgery and the start of
      chemotherapy in the treatment of patients with advanced ovarian cancer. METHODS:
      We stratified patients according to the start of platinum-based chemotherapy in
      group 1 (within 4 weeks from surgery), group 2 (between 4 and 8 weeks) and group
      3 (between 8 and 12 weeks). RESULTS: Three hundred and ninty-four stage III
      ovarian cancer patients were analysed. In the multivariate analysis there were no
      differences in survival according to the interval between surgery and
      chemotherapy among the three groups. The independent prognostic variables were
      type of procedure (p = 0.014), performance status (p = 0.040) and post
      chemotherapy CA-125 (p < 0.0001). CONCLUSIONS: The interval between surgery and
      chemotherapy does not affect outcome.

PMID- 16569494
TI  - The prevalence of axillary lymph-node metastases in patients with pure tubular
      carcinoma of the breast and sentinel node biopsy.
AB  - AIMS: We aimed to evaluate the prevalence of and the risk factors for axillary
      lymph-node metastases in pure tubular carcinoma (PTC) of the breast. The role of
      axillary staging and treatment in PTC was also evaluated. METHODS: Between March
      2001 and August 2004, 33 PTC patients underwent sentinel node (SN) biopsy as a
      part of their surgical treatment. Level I/II axillary clearance was carried out
      in case of tumour positive SN findings. To confirm the correct histological
      diagnosis (PTC, >90% tubular component), the breast tumours were reviewed by an
      expert breast pathologist. RESULTS: The SN were successfully harvested in all
      patients. The median number of SN harvested in the axilla was 3 (range 1-10).
      Nine (27%) of the 33 patients had axillary nodal metastases. The median number of
      metastatic nodes was 1 (range 1-3). The median size of the SN metastases was 0.5
      mm (mean 1.7 mm, range 0.4-5 mm). In six patients, micrometastases were the only
      tumour positive SN findings. The median histological tumour size was similar, 9
      vs 10mm, in patients with or without axillary metastases. The median patient age
      was 54 (range 44-71) and 57 (range 39-80) years, respectively. After the
      histopathological review, six of the 27 patients with true PTC had axillary
      metastases. The review did not significantly change the risk factors for axillary
      metastases. CONCLUSIONS: Every fourth PTC patient has axillary lymph-node
      metastases, most often micrometastases. SN biopsy appears as a feasible method
      for axillary staging in PTC patients.

PMID- 16569495
TI  - Outcome of surgical treatment of pancreatic, peri-ampullary and ampullary cancer
      diagnosed in the south of The Netherlands: a cancer registry based study.
AB  - AIMS: To gain insight into the quality of pancreatic cancer surgery in 10 low
      volume (median sized) hospitals, each serving 150,000-250,000 people, in the
      Comprehensive Cancer Centre South (CCCS) area and of referred patients to
      academic centres to determine the need for further regionalization. METHOD: The
      population-based Eindhoven Cancer Registry was used to select all patients in the
      CCCS area with pancreatic, peri-ampullary and ampullary cancer diagnosed between
      January 1, 1995 and April 30, 2000 (N = 1130). Of those, 124 patients (11%)
      underwent surgical resection (of which 40 were treated in university hospitals
      outside the region). RESULTS: For all pancreatic carcinoma resections, the 3
      month survival rate was 82%, varying from 95% for referred patients to 76% for
      patients treated within the region (p = 0.014). One- and two-year survival rates
      showed no difference between both groups (p = 0.36 and p = 0.55, respectively).
      Surgically treated patients who were referred to university hospitals outside the
      CCCS area were younger, more often male, more often diagnosed with pTNM stage
      III, exhibited less comorbidity and had a higher socio-economic status than
      patients surgically treated within the region. CONCLUSION: Although the results
      are based on small numbers and patient selection probably influenced these
      outcomes, these data seem to support further hospital specialisation, to which
      the surgeons of the CCCS area have committed themselves.

PMID- 16569496
TI  - In vivo and in vitro degradation of a novel bioactive guided tissue regeneration
      membrane.
AB  - The aim of this study was to assess degradation of a novel bioactive guided
      tissue regeneration (GTR) membrane and to quantify the concurrent tissue
      responses. Pieces of membrane composed of poly-l-lactide, poly-d,l-lactide,
      trimethylenecarbonate and polyglycolide were dipped into an N-methyl-2-pyrroline
      (NMP) solution and implanted in the mandibles of 10 sheep. The animals were
      sacrificed at 6-104 weeks. Parallel in vitro degradation was analysed by
      measuring the inherent viscosity, water absorption and remaining mass. One of the
      2 in vitro sets of membranes was prehandled with NMP. At 6-26 weeks in vivo, the
      gradually more degraded implants were surrounded by a fibrous network. At 52 and
      104 weeks, the implants and fibrous networks were non-detectable. Foreign body
      granulomatous reactions were not observed. In vitro, the mass of the NMP-exposed
      membranes diminished linearly over the 2-year period down to 10%, while the non
      NMP-exposed membrane maintained all their mass for the first 16 weeks. The
      membranes without NMP had absorbed significantly less water at weeks 4 and 8 than
      the other group. The inherent viscosity decreased relatively uniformly in the in
      vitro groups. In conclusion, the in vivo degradation was complete in 12 months
      with only mild histologic responses; the degradation in vitro may be slower. NMP
      accelerates the degradation.

PMID- 16569497
TI  - Neurotrophic factor production in human astrocytoma cells by 2,5,6
      tribromogramine via activation of epsilon isoform of protein kinase C.
AB  - It is known that astrocytes secrete several neurotrophic factors to promote the
      survival of neurons. For the treatment of neuronal disorders, low molecular
      weight compounds inducing neurotrophic factor synthesis are useful, because
      neurotrophic factors are polypeptides which cannot cross the blood brain barrier.
      When rat pheochromocytoma (PC-12) cells were cultivated in the medium of human
      astrocytoma cells (1321N1) treated with 2,5,6-tribromogramine, they
      differentiated to neuron-like cells possessing neurites, indicating that 2,5,6
      tribromogramine released neurotrophic factors from 1321N1 cells. In fact, 2,5,6
      tribromogramine increased nerve growth factor (NGF) protein synthesis and
      secretion through mRNA expression. 2,5,6-Tribromogramine inhibited carbachol
      induced phosphoinositide hydrolysis as well as phorbol 12,13-myristate acetate
      did. The inhibition was recovered by bisindolylmaleimide I (GF109203X), a
      specific protein kinase C (PKC) inhibitor, indicating that 2,5,6-tribromogramine
      may activate PKC. The morphological differentiation of PC-12 cells by the medium
      treated with 2,5,6-tribromogramine was also reduced by GF109203X. 2,5,6
      Tribromogramine translocated PKC-epsilon but not PKC-alpha or PKC-zeta, to
      membrane fraction from cytosol fraction. These results indicate that 2,5,6
      tribromogramine promotes the synthesis and secretion of neurotrophic factors
      including NGF in 1321N1 cells via an activation of PKC-epsilon.

PMID- 16569498
TI  - Development of a high analytical performance-tyrosinase biosensor based on a
      composite graphite-Teflon electrode modified with gold nanoparticles.
AB  - The design of a new tyrosinase biosensor with improved stability and sensitivity
      is reported. The biosensor design is based on the construction of a graphite
      Teflon composite electrode matrix in which the enzyme and colloidal gold
      nanoparticles are incorporated by simple physical inclusion. Experimental
      variables such as the colloidal gold loading into the composite matrix, the
      enzyme loading and the potential applied to the bioelectrode were optimized. The
      Tyr-Au(coll)-graphite-Teflon biosensor exhibited suitable amperometric responses
      at -0.10 V for the different phenolic compounds tested (catechol; phenol; 3,4
      dimethylphenol; 4-chloro-3-methylphenol; 4-chlorophenol; 4-chloro-2-methylphenol;
      3-methylphenol and 4-methylphenol). The limits of detection obtained were 3 nM
      for catechol, 3.3 microM for 4-chloro-2-methylphenol, and approximately 20 nM for
      the rest of phenolic compounds. The presence of colloidal gold into the composite
      matrix gives rise to enhanced kinetics of both the enzyme reaction and the
      electrochemical reduction of the corresponding o-quinones at the electrode
      surface, thus allowing the achievement of a high sensitivity. The biosensor
      exhibited an excellent renewability by simple polishing, with a lifetime of at
      least 39 days without apparent loss of the immobilized enzyme activity. The
      usefulness of the biosensor for the analysis of real samples was evaluated by
      performing the estimation of the content of phenolic compounds in water samples
      of different characteristics.

PMID- 16569499
TI  - Biofuel cells and their development.
AB  - This review considers the literature published since 1994 on microbial and
      enzymatic biofuel cells. Types of biofuel cell are classified according to the
      nature of the electrode reaction and the nature of the biochemical reactions. The
      performance of fuel cells is critically reviewed and a variety of possible
      applications is considered. The current direction of development of biofuel cells
      is carefully analysed. While considerable chemical development of enzyme
      electrodes has occurred, relatively little progress has been made towards the
      engineering development biofuel cells. The limit of performance of biofuel cells
      is highlighted and suggestions for future research directions are provided.

PMID- 16569500
TI  - Homopolyvalent antibody-antigen interaction kinetic studies with use of a dual
      polarization interferometric biosensor.
AB  - We used dual-polarization interferometry (DPI) to study the interaction kinetics
      between a 'homopolyvalent' antigen (Ag) and a monoclonal antibody (Ab). A model
      system, which uses a monoclonal Ab against a homopentameric Ag, C-reactive
      protein (CRP), is presented with principle and experiments for the study of the
      interactions between an Ab and an Ag that has multiple identical epitopes. This
      allows evaluation of the dissociation constant (K(D)) and of the binding
      stoichiometry by DPI based on measurements of phase changes of Ab-Ag complexes in
      the transverse magnetic (TM) and transverse electric (TE) polarization modes. The
      average experimental value of K(D) found by the DPI technique for anti-CRP Ab was
      shown to be in close agreement with the value obtained by an indirect competition
      enzyme-linked immunosorbent assay (ELISA). Moreover, the total number of Ab
      combining sites on the DPI sensor chip was calculated, and the binding
      stoichiometry of the surface Ag-Ab complex was obtained. This study illustrates
      the advantages of the DPI method in biosensing in its capacity for simultaneous
      evaluation of the thickness and refractive index (density, mass) of adsorbed
      layers. This allowed a comprehensive analysis of affinity reactions between an Ab
      having two binding sites and a multi-sited Ag.

PMID- 16569501
TI  - Plastic antibody for the recognition of chemical warfare agent sulphur mustard.
AB  - Molecularly imprinted polymers (MIPs) known as plastic antibodies (PAs) represent
      a new class of materials possessing high selectivity and affinity for the target
      molecule. Since their discovery, PAs have attracted considerable interest from
      bio- and chemical laboratories to pharmaceutical institutes. PAs are becoming an
      important class of synthetic materials mimicking molecular recognition by natural
      receptors. In addition, they have been utilized as catalysts, sorbents for solid
      phase extraction, stationary phase for liquid chromatography and mimics of
      enzymes. In this paper, first time we report the preparation and characterization
      of a PA for the recognition of blistering chemical warfare agent sulphur mustard
      (SM). The SM imprinted PA exhibited more surface area when compared to the
      control non-imprinted polymer (NIP). In addition, SEM image showed an ordered
      nano-pattern for the PA of SM that is entirely different from the image of NIP.
      The imprinting also enhanced SM rebinding ability to the PA when compared to the
      NIP with an imprinting efficiency (alpha) of 1.3.

PMID- 16569502
TI  - The Neolithic revolution of bacterial genomes.
AB  - Current human activities undoubtedly impact natural ecosystems. However, the
      influence of Homo sapiens on living organisms must have also occurred in the
      past. Certain genomic characteristics of prokaryotes can be used to study the
      impact of ancient human activities on microorganisms. By analyzing DNA sequence
      similarity features of transposable elements, dramatic genomic changes have been
      identified in bacteria that are associated with large and stable human
      communities, agriculture and animal domestication: three features unequivocally
      linked to the Neolithic revolution. It is hypothesized that bacteria specialized
      in human-associated niches underwent an intense transformation after the social
      and demographic changes that took place with the first Neolithic settlements.
      These genomic changes are absent in related species that are not specialized in
      humans.

PMID- 16569503
TI  - Detailed calculation of K- and L-Auger electron emission intensities following
      radioactive disintegration.
AB  - A program has been set up to calculate the K- and L-Auger electron emissions
      resulting from the radioactive disintegration process, and to study all the
      possible emissions in detail. Due to the fact that only a small number of
      experimental results are available in the measurements of K- and L-Auger
      electrons, the calculated values obtained in this work were compared with the
      other calculated values available. Good agreement was found between the values.
      Some of the results are given as examples.

PMID- 16569504
TI  - MRI myocardial motion and fiber tracking: a confirmation of knowledge from
      different imaging modalities.
AB  - OBJECTIVE: A helical configuration underlies the anatomy of cardiac structure,
      and a structure/function relationship is needed to determine if the ventricular
      myocardial band model defines this spatial relationship. This report explores how
      studies of velocity-encoded phase contrast magnetic resonance imaging (MRI) for
      myocardial motion and fiber tracking algorithms that imply fiber orientations can
      (a) quantify regional myocardial wall motion of the entire heart, (b) determine
      if these motion of implied fiber orientation link with the helical heart model,
      and (c) reveal if this new knowledge correlates with imaging information from
      other different imaging modalities. METHODS: Accumulated left ventricular motion
      patterns that accurately differentiate radial (i.e. contraction and expansion),
      rotational (i.e. twisting and untwisting), and longitudinal (i.e. lengthening and
      shortening) motion components are correlated with structure/function data
      achieved by sonomicrometer crystals, echocardiography, corrosion casts, and MUGA
      recordings. RESULTS: Acceleration fiber tracking to determine fiber orientation
      and cardiac motion during the ejection and rapid filling phases of the cardiac
      cycle corresponded to maximal force displayed by ultrasonic crystals placed into
      the angulation of the presumed functional units of the descending and ascending
      segments of the apical loop of the helical ventricular myocardial band, and
      motion by echocardiographic recordings. These integrated findings imply a
      favourable interaction of MRI with the myocyte orientation of the helical
      ventricular myocardial band. CONCLUSIONS: These composite findings indicate that
      phase contrast MRI techniques for high temporal resolution velocity mapping
      during cardiac motion and myocardial fiber tracking confirm other technologies,
      and centralize the capacity of MRI to link other imaging methods together
      relative to a single helical structural model. The close agreement amongst a
      spectrum of imaging studies provide a very powerful integration that transcends a
      single look; the same thing is observed by each component of global technology,
      thereby implying that the helical ventricular band is the structural basis for
      these functional changes.

PMID- 16569505
TI  - Fetal cell carcinogenesis of the thyroid: theory and practice.
AB  - A novel hypothesis of thyroid carcinogenesis, the "fetal cell carcinogenesis"
      hypothesis, in which cancer cells are derived from the remnants of three types of
      fetal thyroid cells, instead of normal thyroid follicular cells, is proposed. In
      this hypothesis, thyroid cancer cells are generated from fetal cells by
      proliferation without differentiation and oncogenes play an oncogenic role by
      preventing fetal cells from differentiating. This hypothesis explains well the
      clinical and biological features and recent molecular evidence of thyroid
      carcinoma. It underscores the importance of clarifying the molecular mechanism of
      thyroid development and the identification of fetal thyroid cells, especially
      thyroid stem cells (TSCs), since such data will lead to better understanding of
      thyroid carcinoma and other thyroid diseases.

PMID- 16569506
TI  - Method for large-scale isolation and purification of R-phycoerythrin from red
      alga Polysiphonia urceolata Grev.
AB  - R-phycoerythrin was isolated and purified from a red alga, Polysiphonia urceolata
      Grev, using Streamline column combined with ion-exchange chromatography or
      hydroxyapatite chromatography. The purity of R-phycoerythrin isolated by
      Streamline column was up to 1.66 and the yield of R-phycoerythrin could be as
      high as 0.68 mg/g frozen P. urceolata. All the eluates from Streamline column
      were divided into two equivalent parts, respectively. One part was pumped into
      the ion-exchange column loaded with Q-Sepharose and the other was applied to the
      adsorption column loaded with hydroxyapatite. The purities of R-phycoerythrin
      purified using these two methods were both up to 3.26, more than 3.2 the commonly
      accepted criterion. The yield of purified R-phycoerythrin from the ion-exchange
      chromatography was 0.40 mg/g frozen P. urceolata and that from the hydroxyapatite
      chromatography could reach 0.34 mg/g frozen P. urceolata. The purified protein
      had three absorption peaks at 498, 535, and 565 nm and displayed a fluorescence
      maximum at 580 nm, which was consistent with the typical spectrum of R
      phycoerythrin. The purified R-PE was also identified with electrophoresis. Only
      one single protein band appeared on native-PAGE with silver staining. SDS-PAGE
      demonstrated the presence of one 20 kDa major subunit, and one low intensity band
      corresponding to 33 kDa subunit. The results indicate that using the expanded bed
      adsorption combined with ion-exchange chromatography or hydroxyapatite
      chromatography, R-phycoerythrin can be purified from frozen P. urceolata on large
      scale.

PMID- 16569507
TI  - Regulation of fertilization-initiated [Ca2+]i oscillations in mammalian eggs: a
      multi-pronged approach.
AB  - The calcium ([Ca(2+)](i)) oscillations associated with mammalian fertilization
      and required to induce egg activation occur during M-phase stages of the cell
      cycle. The molecular mechanisms underlying this regulation remain unproven and
      may be multi-layered. Type 1 inositol 1,4,5-trisphosphate receptors (IP(3)R-1),
      which mediate [Ca(2+)](i) release during fertilization, have emerged as key
      regulatory units because they contain multiple phosphorylation consensus sites
      and undergo changes in cellular location and mass prior to and following
      fertilization. Hence, control of IP(3)R-1 function together with regulation of
      PLCzeta activity, the putative sperm factor, may combine to impart cell cycle and
      species-specific [Ca(2+)](i) oscillations characteristic of mammalian
      fertilization.

PMID- 16569508
TI  - Loss in mechanical contact of cementless acetabular prostheses due to post
      operative weight bearing: a biomechanical model.
AB  - The primary stability of cementless acetabular components is a prerequisite for
      their clinical success. The target of the present study was to analyse possible
      effects of post-operative joint loading on the initial mechanical stability of a
      press-fitted acetabular prosthesis. For this purpose, a three-dimensional finite
      element model of the pelvic bone with acetabular reconstruction was set-up. The
      analysis included two steps: (1) simulation of the prosthesis press-fit
      implantation and (2) simulation of the instant of peak resultant hip loading
      during the one-legged stance. The difference between the contact pressures at the
      bone/implant interface, at the end of the second step and those at the end of the
      first step was calculated and assumed as an index of variation in mechanical
      contact due to post-operative weight bearing. The results show that, due to hip
      loading, contact pressures given by press-fit increase in the postero-superior
      acetabular region but decrease in the antero-inferior acetabular region. The
      calculated area in which the contact pressures decrease extend to about 30% of
      the total contact surface. These results imply that post-operative joint loading
      significantly reduces the mechanical stability given by press-fit. The decrease
      in contact pressures at the bone/implant interface may result in a lack of
      osteointegration, possibly hindering the implant secondary stability. It may also
      create a route for wear debris, possibly favouring periprosthetic osteolysis,
      which may lead to further loss in contact and clinical failure of the implant due
      to loosening.

PMID- 16569509
TI  - Toward a veterinary informatics research agenda: an analysis of the PubMed
      indexed literature.
AB  - PURPOSE: Veterinary medicine and human health are inextricably intertwined.
      Effective tracking of veterinary information - veterinary informatics - impacts
      not only veterinary medicine, but also public health, informatics research, and
      clinical care. However, veterinary informatics has received little attention from
      the general biomedical informatics community. METHODS: To identify both active
      and under-researched areas in veterinary informatics, we retrieved Medical
      Subject Heading (MeSH) descriptors for veterinary informatics-related citations
      and analyzed them by topic category, animal type, and journal. RESULTS: We found
      that the categories of veterinary informatics with the most growth were
      information/bibliographical retrieval, hardware/programming, and
      radiology/imaging. Less than two articles per year were published in the areas of
      computerized veterinary medical records, clinical decision support, standards,
      and controlled vocabularies. Veterinary informatics articles primarily address
      production animals such as cattle and sheep, and companion animals such as cats
      and dogs. Six journals account for 31% of the veterinary informatics literature,
      35 journals account for 66%. CONCLUSIONS: Veterinary informatics remains an
      embryonic field with relatively few publications. With the exception of
      radiology/imaging, published articles are primarily focused on non-clinical areas
      such as hardware/programming and information retrieval. There are very few
      publications on controlled vocabularies, standards, methodologies for integrating
      disparate systems, computerized medical records, clinical decision support
      systems, and system usability. The lack of publications in these areas may hamper
      efforts to collect and track animal health data at a time when such data are
      potentially critical to human health.

PMID- 16569510
TI  - Genetic variants of parvovirus B19 identified in the United Kingdom: implications
      for diagnostic testing.
AB  - BACKGROUND: Discrepant results in diagnostic parvovirus B19 PCR assays have been
      observed with strains showing nucleotide sequence variation. OBJECTIVES AND STUDY
      DESIGN: To perform phylogenetic analysis on two parvovirus B19 strains that gave
      discrepant PCR results. RESULTS: One strain was found to be genotype 2; the
      second strain was genotype 3. CONCLUSIONS: Parvovirus B19 genotypes 2 and 3
      strains were identified in diagnostic samples of UK origin following the
      investigation of discrepant PCR results. More structured investigations are
      needed to estimate the prevalence of these variants. In the meantime, diagnostic
      PCR results should be interpreted cautiously when they are at variance with
      serological testing. Manufacturers of PCR kits for the detection of B19 sequences
      will need to consider re-designing their primers.

PMID- 16569512
TI  - Drug-resistant tuberculosis in Cuba. Results of the three global projects.
AB  - SETTING: The spread of multidrug-resistant tuberculosis (MDR TB) in the world
      remains a major public health problem. Surveillance of anti-TB drug resistance is
      therefore an essential tool for monitoring the effectiveness of TB control
      program and, through policy development, for improving national and global TB
      control. OBJECTIVE: To determine the prevalence of anti-TB drug resistance in
      Cuba during the execution of the three global projects. DESIGN: Drug-resistance
      was determined using the proportion method in 1528 Mycobacterium tuberculosis
      strains to first line anti-TB drugs. RESULTS: Resistance in new cases was 8.3%,
      4.6% and 5.0%; MDR was 0.7%, 0% and 0.3% in the first (1997), second (2000) and
      third (2004) global projects, respectively. In new cases, none showed resistance
      to the four drugs. There were among previously treated cases statistically
      significant decreases in the prevalence of resistance to at least one drug when
      comparing the results obtained in the three global projects. CONCLUSIONS: The
      contributed data through Cuba demonstrated that our country is relatively free of
      MDR strains, reflecting the good National Control Program and the possibility of
      TB elimination in Cuba.

PMID- 16569513
TI  - A mutant type 2 herpes simplex virus deleted for the protein kinase domain of the
      ICP10 gene is a potent oncolytic virus.
AB  - Replication-selective oncolytic herpes simplex virus (HSV) has shown considerable
      promise as an antitumor agent. Although the current oncolytic HSVs were
      exclusively constructed from HSV-1, HSV-2 has several unique features that could
      be exploited to convert the virus to an oncolytic agent. The N-terminus of the
      HSV-2 ICP10 gene product contains a well-defined serine/threonine protein kinase
      (PK) domain, which can activate the Ras/MEK/MAPK mitogenic pathway and thus
      facilitate efficient HSV-2 replication. Because the Ras signaling pathway is a
      key regulator of normal cell growth and malignant transformation, it is
      aberrantly activated in many human tumors. Here we report that a mutant HSV-2
      (FusOn-H2), constructed by replacing the PK domain of ICP10 with the gene
      encoding the green fluorescent protein, can selectively replicate in and thus
      lyse tumor cells. Moreover, infection of FusOn-H2 led to syncytia formation in
      tumor cells, providing an additional tumor-destroying mechanism. A single
      moderate-dose injection of FusOn-H2 into established breast cancer xenografts
      completely eradicated the tumors in more than 80% of the animals, leading to
      their long-term survival. We conclude that this HSV-2 mutant is a safe and potent
      oncolytic agent useful for the treatment of malignant solid tumors such as breast
      cancer.

PMID- 16569514
TI  - Repair of DNA interstrand cross-links: interactions between homology-dependent
      and homology-independent pathways.
AB  - DNA interstrand cross-links (ICLs) are complex DNA lesions generated by
      bifunctional alkylating agents, a class of compounds extensively used in cancer
      chemotherapy. Formation of an ICL covalently links the opposing strands of the
      double helix and results in severe disruptions of normal DNA functions, such as
      replication, transcription, and recombination. Because of the structural
      complexity, ICLs are most likely recognized by a variety of repair recognition
      proteins and processed through multiple mechanisms. To study the involvement of
      different repair pathways in ICL processing, we examined a variety of mammalian
      mutants with distinct DNA repair deficiencies. We found that the presence of ICLs
      induces frequent recombination between direct repeat sequences, suggesting that
      the single-strand annealing pathway may be an important mechanism for the removal
      of ICLs situated within direct repeats. Unlike recombination-independent ICL
      repair, ICL-induced single-strand annealing does not require the nucleotide
      excision repair (NER) mechanism. In cells defective in the mismatch repair
      protein Msh2, the level of recombination-independent ICL repair was significantly
      increased, suggesting that processing by the mismatch repair mechanism may lead
      to recombinational repair of ICLs. Our results suggest that removal of ICLs may
      involve two error-prone mechanisms depending on the sequence context of the cross
      linked site.

PMID- 16569516
TI  - Simultaneous electrochemiluminescence determination of sulpiride and tiapride by
      capillary electrophoresis with cyclodextrin additives.
AB  - Sulpiride and tiapride are often used in the treatment of depression,
      schizophrenia and psychopathology of senescence, gastric or duodenal ulcers and
      are also partly excreted by kidney. This work developed a simple and sensitive
      method for their simultaneous monitoring in human urine based on capillary
      electrophoresis coupled with electrochemiluminescence detection by end-column
      mode. beta-Cyclodextrin (beta-CD) was used as an additive to the running buffer
      to obtain the absolute separation of sulpiride and tiapride. Under optimized
      conditions the proposed method displayed a linear range from 1.0 x 10(-7) to 1.0
      x 10(-4) M for both sulpiride and tiapride with the correlation coefficients more
      than 0.995 (n = 6). Their limits of detection were 1.0 x 10(-8) M (45 amol) and
      1.5 x 10(-8) M (68 amol) at a signal to noise ratio of 3, respectively. The
      relative standard deviations for six determinations of 2.0 microM sulpiride and
      3.0 microM tiapride were 1.8 and 2.5%, respectively. For practical application an
      extract step with ethyl acetate at pH 11 was performed to eliminate the influence
      of ionic strength in sample. The recoveries of sulpiride and tiapride at
      different levels in human urine were between 84 and 95%, which showed that the
      method was valuable in clinical and biochemical laboratories for monitoring
      sulpiride and tiapride for various purposes.

PMID- 16569517
TI  - Separation of poly(amidoamine) (PAMAM) dendrimer generations by dynamic coating
      capillary electrophoresis.
AB  - The separation of compounds possessing amino groups (peptides, proteins,
      polyamino compounds) by capillary zone electrophoresis suffers from the
      interaction (sticking) of these solutes with the capillary wall. This sticking
      can result in the absence or incomplete separation of compounds or even in their
      retention in the capillary. Polyamidoamine (PAMAM) dendrimers are a class of
      spherical polymers with primary amino groups at the surface. These compounds can
      be separated reasonably well at acidic pH but not at neutral pH. A new method
      based on the dynamic coating of the capillary was developed for the separation of
      these compounds at pH 7.4. The method comprises separation in a fused-silica
      capillary (57 cm total length, 50 cm to the detector, ID 75 microm) and a
      background electrolyte consisting of a Tris-phosphate buffer (50 mmol/L, pH 7.4)
      and 0.05% (w/v) polyethyleneimine. This system is suitable for the separation of
      7 generations of dendrimers (generations 0-6). The dynamic coating agent
      (polyethyleneimine) also improves the separation at acid pH.

PMID- 16569515
TI  - Esc4/Rtt107 and the control of recombination during replication.
AB  - When replication forks stall during DNA synthesis, cells respond by assembling
      multi-protein complexes to control the various pathways that stabilize the
      replication machinery, repair the replication fork, and facilitate the
      reinitiation of processive DNA synthesis. Increasing evidence suggests that cells
      have evolved scaffolding proteins to orchestrate and control the assembly of
      these repair complexes, typified in mammalian cells by several BRCT-motif
      containing proteins, such as Brca1, Xrcc1, and 53BP1. In Saccharomyces
      cerevisiae, Esc4 contains six such BRCT domains and is required for the most
      efficient response to a variety of agents that damage DNA. We show that Esc4
      interacts with several proteins involved in the repair and processing of stalled
      or collapsed replication forks, including the recombination protein Rad55.
      However, the function of Esc4 does not appear to be restricted to a Rad55
      dependent process, as we observed an increase in sensitivity to the DNA
      alkylating agent methane methylsulfonate (MMS) in a esc4Deltarad55Delta mutant,
      as well as in double mutants of esc4Delta and other recombination genes, compared
      to the corresponding single mutants. In addition, we show that Esc4 forms
      multiple nuclear foci in response to treatment with MMS. Similar behavior is also
      observed in the absence of damage when either of the S-phase checkpoint proteins,
      Tof1 or Mrc1, is deleted. Thus, we propose that Esc4 associates with ssDNA of
      stalled forks and acts as a scaffolding protein to recruit and/or modulate the
      function of other proteins required to reinitiate DNA synthesis.

PMID- 16569518
TI  - Determination of monoamines in urine by capillary electrophoresis with field
      amplified sample stacking and amperometric detection.
AB  - A simple, rapid and low-cost method using capillary electrophoresis coupled with
      field-amplified sample stacking and electrochemical detection was developed for
      the separation and determination of monoamines. In this present work, a
      systematic study of the parameters (pH value and concentration of electrophoretic
      buffer, composition of sample solvent, injection voltage and time) affecting
      separation and on-line concentration of monoamines has been performed enabling
      the detection sensitivity of these monoamines to be improved by 5,000 times
      compared with the conventional electrokinetic injection. This developed method
      was applied to the direct analysis of these monoamines in human urine without off
      line sample preconcentration. Due to the requirement for urine dilution to
      minimize the detrimental effects of high salt on analyte stacking, the real
      sensitivity improvement is about 50-fold when applying the optimized method to
      urine samples. In order to quantitate these monoamines accurately, internal
      standard calibration curves were constructed with standard monoamines in presence
      of salt with similar concentration as in human urine. In the method validation,
      the calibration curves were linear over a range of 1.0 x 10(-9) to 2.5 x 10(-8)
      mol/L for each monoamine and the limits of detection (signal to noise ratio of 3)
      for these monoamines were in the sub-nmol/L concentration range (6.0 x 10(-10)
      mol/L).

PMID- 16569519
TI  - Detection of human butyrylcholinesterase-nerve gas adducts by liquid
      chromatography-mass spectrometric analysis after in gel chymotryptic digestion.
AB  - To verify the exposure to nerve gas, a method for detecting human
      butyrylcholinesterase (BuChE)-nerve gas adduct was developed using LC
      electrospray mass spectrometry (ESI-MS). Purified human serum BuChE was incubated
      with sarin, soman or VX, and the adduct was purified by sodium dodecylsulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and digested in gel by treatment
      with chymotrypsin. The resulting peptide mixture was subjected to LC-ESI-MS. From
      the chymotryptic digest of untreated human BuChE, one peak corresponding to the
      peptide fragment containing the active center serine residue was detected on the
      extracted ion chromatogram at m/z 948.5, and the sequence was ascertained to be
      "GESAGAASVSL" by MS/MS analysis. From the chymotryptic digest of the human BuChE
      sarin adduct, a singly charged peptide peak was detected on the extracted ion
      chromatogram at m/z 1,069.5, and the sequence was ascertained to be "GEXAGAASVSL"
      by MS/MS analysis (X denotes isopropylmethylphosphonylated serine). The
      difference in molecular weight (120.0 Da) between the active center peptide
      fragments corresponding to the untreated BuChE and BuChE-sarin adduct was assumed
      to be derived from the addition of an isopropyl methylphosphonyl moiety to the
      serine residue. The formation of human BuChE adducts with soman, VX and an aged
      soman adduct was confirmed by detecting the respective active center peptide
      fragments using LC-ESI-MS. To apply the established method to an actual
      biological sample, human serum was incubated with VX, and the adduct was purified
      by procainamide affinity chromatography followed by SDS-PAGE. After chymotryptic
      in gel digestion, the ethylphosphonylated active center peptide fragment could be
      detected, and the structure of the residue was ascertained by LC-ESI-MS analysis.

PMID- 16569520
TI  - Validation of liquid/liquid extraction method coupled with HPLC-UV for
      measurement of ribavirin plasma levels in HCV-positive patients.
AB  - Measurement of ribavirin plasma levels in HCV-positive patients have been shown
      to be useful in order to optimise individual ribavirin exposure. Efficacy and
      toxicity of this drug are shown to be concentration-dependant. A simple HPLC-UV
      method was developed and validated, which has an easy liquid/liquid extraction,
      sensitive limit of detection, without any interference peaks, reproducible and
      linear over the range of clinical relevant concentrations. The assay warrants
      further evaluation as a tool for ribavirin therapeutic drug monitoring in HCV
      positive patients.

PMID- 16569521
TI  - Mucosal features and granulocyte-monocyte-apheresis in steroid
      dependent/refractory ulcerative colitis.
AB  - BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early
      characteristic of inflammation and the main histological feature of active
      ulcerative colitis. Mucosal healing has recently been indicated as an important
      tool in the evaluation of response to treatment. While several studies have
      stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical
      remission in active ulcerative colitis, few data are available on mucosal
      features. AIM: Aim of this study was to assess the effects of granulocyte
      monocyte-apheresis on clinical and mucosal features in patients with ulcerative
      colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From
      April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years,
      range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six
      pancolitis) dependent/refractory upon steroids were enrolled. Each patient was
      treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis.
      Patients were evaluated at baseline and 1 week after the last apheresis by means
      of Global Physician Assessment, quality of life features, laboratory tests
      (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine),
      endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal
      healing was observed in 3 out of 12 patients, partial mucosal healing in 8
      patients and no change in 1 patient. Clinical response was complete in 8 out of
      12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis
      induces an improvement both in clinical and mucosal lesions in steroid
      dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte
      infiltration and the improvement in mucosal lesions are accompanied by a
      reduction in faecal calprotectine.

PMID- 16569522
TI  - Diabetic control after total pancreatectomy.

PMID- 16569523
TI  - Comparison between subjective and objective assessment of the long-term results
      after the Heller-Dor operation in patients affected by oesophageal achalasia.
AB  - INTRODUCTION: Nowadays the subjective assessment of Health-Related Quality of
      Life after surgery for achalasia is often associated with the instrumental
      methods in order to evaluate long-term results of therapy. AIMS: To assess the
      long-term objective and subjective results of the surgical treatment of achalasia
      and to study the correlation between clinical-instrumental methods and those
      based on the patient's self-assessment and on Health-Related Quality of Life
      questionnaires. METHODS: One hundred and twenty-four patients consecutively
      submitted to trans-abdominal Heller-Dor operation were periodically followed up
      with clinical examination, endoscopy, barium swallow and manometry. The Health
      Related Quality of Life was assessed using the 36 item short form (SF-36) and the
      Psychological General Well-Being Index questionnaire. The statistical comparison
      between the results of the self-assessment questionnaires and the long-term
      clinical-instrumental result was calculated by means of linear regression
      analysis. RESULTS: Over the years, 123 patients underwent at least one complete
      clinical-instrumental check-up and filled the self-assessment questionnaires.
      Mean follow-up was 105 months (range 12-288) with a median of 82.5 months. The
      result of the surgery was considered satisfactory in 93.5% of the patients, while
      the reflux oesophagitis observed in 6.5% of the cases was the main cause of
      failure. Clinical scores for dysphagia and for gastro-oesophageal reflux symptoms
      were significantly reduced after surgery. The results of the SF-36 and
      Psychological General Well-Being Index questionnaires were in our population very
      high and clinical correlation (p<0.05) emerged in physical function, in role
      physical, in mental health and in vitality domains of SF-36 questionnaire, and in
      self-control and general health scales of Psychological General Well-Being Index
      questionnaire. CONCLUSIONS: Health-Related Quality of Life questionnaires can be
      considered valid aids in evaluating surgical results, but the clinical
      instrumental evaluation remains the cardinal point of every long-term assessment
      in order to diagnose complications, the disease-related conditions of the patient
      and to acquire reliable data on which scientific discussion can be based.

PMID- 16569524
TI  - Capsule endoscopy findings in patients with suspected Crohn's disease and
      biochemical markers of inflammation.
AB  - BACKGROUND: Because it provides a direct view of superficial lesions in the small
      bowel, capsule endoscopy is a promising diagnostic tool for studying patients
      with suspected Crohn's disease undetected by conventional modalities. AIM: To
      assess the role of capsule endoscopy in the diagnosis of patients with suspected
      Crohn's disease. PATIENTS AND METHODS: Thirty-eight patients (16 males, mean age
      46.2 years) with suspected Crohn's disease but negative at conventional imaging
      were examined using capsule endoscopy. They were divided into 2 groups: 12
      patients with ongoing symptoms (Group 1), and 26 with ongoing symptoms and
      biochemical markers of inflammation (Group 2). Capsule endoscopy findings were
      classified as diagnostic (multiple erosions/ulcerations), suspicious (<or=3
      erosions/ulcerations), non-specific and normal. RESULTS: Capsule endoscopy
      findings were diagnostic for Crohn's disease in 13 (34.2%) patients, suspicious
      in 2 (5.3%), non-specific in 4 (10.5%) and normal in 19 (50%), with an overall
      detection rate of 39.5%. The yield of positive findings was 8.3% in Group 1 and
      46.2% in Group 2 (p=0.022). Capsule endoscopy findings prompted specific measures
      or patient management changes in 39.5% of patients. CONCLUSIONS: Capsule
      endoscopy has a high diagnostic yield in patients with suspected Crohn's disease
      and both clinical and biochemical markers of inflammation.

PMID- 16569525
TI  - Is nesiritide really that good or that bad?

PMID- 16569527
TI  - Cardiac resynchronization therapy: a regulatory perspective.

PMID- 16569528
TI  - From efficacy to safety concerns: a STEP forward or a step back for clinical
      research and intercessory prayer? The Study of Therapeutic Effects of
      Intercessory Prayer (STEP).

PMID- 16569529
TI  - Unraveling the pathophysiology of acute heart failure: an inflammatory proposal.

PMID- 16569530
TI  - The clinically unrecognized Q-wave myocardial infarction: what does it mean and
      what should we do?

PMID- 16569531
TI  - A perspective on antiarrhythmic drug therapy to treat atrial fibrillation: there
      remains an unmet need.
AB  - Because presently available antiarrhythmic drugs are neither as highly
      efficacious nor as safe as desirable for the prevention of atrial fibrillation
      (AF), rate control-versus-rhythm control trials for the treatment of AF were
      evaluated. They demonstrated that rate control is not simply a therapeutic
      fallback option if rhythm control should fail, but rather, it is a legitimate
      primary therapeutic option. Nevertheless, there remain many reasons to consider
      maintenance of sinus rhythm (rhythm control) over AF (rate control) if only there
      were antiarrhythmic agents that could provide this treatment more effectively and
      safely. In fact, an important analysis of the AFFIRM trial data indicated that
      rhythm control offers a significant survival advantage over rate control if it
      could be safely achieved. Therein lie an important clinical dilemma and an unmet
      need. Sinus rhythm is good, but we need better ways to maintain it effectively
      and safely.

PMID- 16569532
TI  - Rescue percutaneous coronary intervention after failed fibrinolytic therapy: have
      expectations been met?
AB  - BACKGROUND: Reperfusion therapy for acute myocardial infarction has
      revolutionized modern cardiovascular care. METHODS AND RESULTS: Two strategies
      have been tested widely: fibrinolytic therapy and percutaneous coronary
      intervention (PCI). Fibrinolytic therapy has the advantage that it can be given
      in many medical care institutions that do not have immediate access to
      catheterization laboratories. Unfortunately, in a substantial number of patients,
      fibrinolytic therapy may not achieve optimal results, and a strategy of rescue or
      salvage PCI may be undertaken. There is a relative paucity of evidence-based
      outcomes on which to judge the merits of rescue PCI, although the volume is
      increasing. CONCLUSIONS: At present, several recommendations can be offered: (1)
      implementation of a policy of rescue PCI requires clear guidelines of patient
      selection, training of personnel, logistics of patient movement, and outcomes
      assessment; and (2) there needs to be heightened awareness with a high index of
      suspicion about the potential failure of fibrinolytic therapy.

PMID- 16569533
TI  - The REduction of Atherothrombosis for Continued Health (REACH) Registry: an
      international, prospective, observational investigation in subjects at risk for
      atherothrombotic events-study design.
AB  - BACKGROUND: The risk of atherothrombosis is a large health care burden worldwide.
      With its global prevalence, there is a need to understand all the associated risk
      factors, both old and new, and their interdependencies in the development of this
      complex disease leading to myocardial infarction, ischemic stroke, and vascular
      death and, thus, the major cause of mortality throughout the world. METHODS: The
      REACH Registry sought to compile an international data set to extend our
      knowledge of atherothrombotic risk factors and ischemic events in the outpatient
      setting. The Registry will recruit approximately 68,000 outpatients in 44
      countries across 6 major regions (Latin America, North America, Europe, Asia, the
      Middle East, and Australia) from >5000 physician outpatient practices. Patients
      aged > or =45 years with at least 3 atherothrombotic risk factors or documented
      cerebrovascular, coronary artery, or peripheral arterial disease will be
      enrolled. Medical history, risk factors, demographic information, and management
      will be collected at baseline, and clinical events that occur during the follow
      up period of up to 2 years in duration will be recorded. CONCLUSION: The REACH
      Registry offers an opportunity to provide a better understanding of the
      prevalence and clinical consequences of atherothrombosis in the outpatient
      setting in a wide range of patients from different parts of the world.

PMID- 16569534
TI  - Concerning the mechanism of pexelizumab's benefit in acute myocardial infarction.
AB  - BACKGROUND: The COMplement inhibition in Myocardial infarction treated with
      Angioplasty (COMMA) trial previously demonstrated an unexpected dose-dependent
      reduction in 90-day mortality after bolus/infusion of pexelizumab despite no
      reduction in the primary end point of myocardial infarction (MI) size. We
      examined whether the mortality benefit was related to established modulators of
      clinical benefit such as baseline demographics, time to treatment from symptom
      onset, myocardial perfusion post-percutaneous coronary intervention (PCI), and
      extent of ST resolution. METHODS AND RESULTS: Eight hundred fourteen patients
      were randomized into 3 groups; (1) placebo, (2) pexelizumab bolus 2.0 mg/kg and
      placebo infusion for 20 hours, and (3) pexelizumab bolus 2.0 and 0.05 mg/kg per
      hour infusion for 20 hours commencing 4 hours after the bolus. Subjects presented
      with ST elevation MI within 6 hours of symptom onset and underwent PCI, creatine
      kinase (CK), and CK-MB measurements taken sequentially to define CK-MB area under
      the curve (AUC) and sequential ECG's defined ST resolution and QRS infarct size.
      Whereas mortality for both placebo and bolus pexelizumab groups rose during later
      time after presentation, it remained low and did not change appreciably during
      the 6-hour randomization window when patients received pexelizumab bolus
      infusion. Amplification of the mortality benefit was evident in patients with the
      highest quartile of hemodynamic compromise, that is, heart rate > or = 90
      beat/min and systolic blood pressure < or = 118 mm Hg (3.2% vs 11.3% P = .004). A
      significant interaction between treatment assignment and hemodynamic status (P =
      .013) existed after adjusting for age, race, and MI location. Clinical benefit
      was not related to infarct size, extent of ST elevation, or evidence of
      angiographic or electrocardiographic reperfusion. CONCLUSIONS: These data raise
      the possibility that the clinical benefit of pexelizumab is mediated through
      novel pathways such as reduction in apoptosis or other mechanisms.

PMID- 16569535
TI  - The greatest benefit of enoxaparin over unfractionated heparin in acute coronary
      syndromes is achieved in patients presenting with ST-segment changes: the
      Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) Electrocardiogram Core
      Laboratory Substudy.
AB  - BACKGROUND: We undertook a prospective electrocardiogram (ECG) substudy in the
      ESSENCE trial and hypothesized that patient subgroups with ST-segment deviation
      would experience greater benefit from enoxaparin, as compared with unfractionated
      heparin (UFH). METHODS: Of the 3171 patients in the trial, 3087 had a qualifying
      ECG available for analysis by the core laboratory. Patients were divided into 4
      mutually exclusive groups based upon the qualifying ECG: (1) ST-segment
      elevation, (2) ST-segment depression, (3) T-wave inversions, or (4) others.
      RESULTS: The 30-day and 1-year primary outcomes (death, myocardial infarction, or
      recurrent angina) were significantly lower among patients with ST elevation or ST
      depression who received enoxaparin, as compared with UFH (20.8% vs 28.0%, P =
      .0019 and 32% vs 40.4%, P = .0011, respectively). The greatest absolute benefit
      of enoxaparin over UFH was seen in patients with ST depression (primary end point
      at 30 days, 24.6% vs 32.4%, P = .018; at 1 year, 35.5% vs 44.5%, P = .012).
      CONCLUSION: Specific recognition of patients with ST-segment depression appears
      to identify those not only at high risk for adverse outcome, but also patients
      most likely to derive the greatest benefit from enoxaparin, as compared with UFH
      therapy.

PMID- 16569536
TI  - Comparison of very early treatment with either fibrinolysis or percutaneous
      coronary intervention facilitated with abciximab with respect to ST recovery and
      infarct-related artery epicardial flow in patients with acute ST-segment
      elevation myocardial infarction: the Swedish Early Decision (SWEDES) reperfusion
      trial.
AB  - BACKGROUND: Results from a number of studies indicate that primary percutaneous
      coronary intervention (PCI) is superior to fibrinolysis for treatment of acute ST
      elevation myocardial infarction. Modern adjunctive antithrombotic treatment with
      systematic use of low-molecular-weight heparins, fibrin-specific thrombolysis,
      and glycoprotein IIb/IIIa receptor inhibitors may improve the outcome compared
      with what was achieved in previous studies. METHODS: Patients with ST-elevation
      myocardial infarction were randomized to receive enoxaparin followed by reteplase
      (group A; n = 104) or enoxaparin followed by abciximab and transfer to invasive
      center for optional PCI (group B; n = 101). Primary end points were ST-segment
      resolution 120 minutes and TIMI flow at coronary angiography 5 to 7 days after
      randomization. RESULTS: Forty-two percent of the patients started therapy in the
      prehospital phase. Time from symptom to treatment was 114 minutes in group A and
      202 minutes in group B. Baseline characteristics were similar in the 2 groups.
      Sixty-four percent in group A and 68% in group B had ST resolution of > 50% at
      120 minutes (not significant). At control angiography, 54% in the fibrinolytic
      group and 71% in the invasive group had TIMI 3 flow (P = .04). At 30 days, the
      composite of death, stroke, or reinfarction occurred in 8% in the fibrinolytic
      group compared with 3% in the invasive group (not significant). CONCLUSIONS:
      Despite much shorter time delay to start of fibrinolysis than PCI, this did not
      result in signs of superior myocardial reperfusion. Epicardial flow in the
      infarct-related artery was better after invasive therapy, and there was a trend
      toward better clinical outcome after this treatment compared with after
      fibrinolysis.

PMID- 16569537
TI  - Effect on coronary flow velocity reserve in patients with type 2 diabetes
      mellitus: comparison between angiotensin-converting enzyme inhibitor and
      angiotensin II type 1 receptor antagonist.
AB  - BACKGROUND: The effects of angiotensin antagonists on coronary circulation in
      type 2 diabetes are unclear. We aimed to assess whether 4 weeks of treatment with
      angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor
      antagonist improves coronary flow velocity reserve (CFVR) in patients with type 2
      diabetes. METHODS: Twenty-four asymptomatic patients with type 2 diabetes were
      randomly assigned to temocapril (2 mg/d) or candesartan (8 mg/d). Coronary flow
      velocity reserve, calculated as the ratio of adenosine-induced hyperemic to basal
      coronary flow velocity, was measured with transthoracic Doppler echocardiography.
      Coronary flow velocity reserve measurement and venous blood sampling were
      performed before and after 4 weeks of treatment. We also obtained CFVR and venous
      blood data in the 8 healthy controls. RESULTS: Coronary flow velocity reserve was
      significantly lower in patients than controls (temocapril group 2.74 +/- 0.28,
      candesartan group 2.65 +/- 0.30, controls 3.53 +/- 0.23, P < .0001 for both,
      respectively). Blood pressure was reduced in both diabetic groups (n = 12 each)
      similarly 4 weeks after treatment. There were no significant differences between
      the 2 groups in venous blood data before or after treatment. However, CFVR
      increased significantly in the temocapril group (2.74 +/- 0.28 to 3.31 +/- 0.36,
      P < .0001), but not in the candesartan group (2.65 +/- 0.30 to 2.71 +/- 0.43, P =
      ns). CONCLUSIONS: Coronary flow velocity reserve in patients with type 2 diabetes
      improved after treatment with temocapril but not with candesartan, suggesting
      that angiotensin-converting enzyme inhibitor, but not angiotensin II type 1
      receptor antagonist, might have beneficial effects on coronary microangiopathy
      associated with type 2 diabetes.

PMID- 16569538
TI  - Unrecognized myocardial infarction: the association with cardiopulmonary symptoms
      and mortality is mediated via echocardiographic abnormalities of global
      dysfunction instead of regional dysfunction: the Olmsted County Heart Function
      Study.
AB  - BACKGROUND: There are very few data describing the association of
      electrocardiogram-based unrecognized myocardial infarction (ECG-UMI) with
      nonanginal cardiopulmonary symptoms, echocardiographic abnormalities, and
      mortality in the community. METHODS: We studied 2042 Olmsted County residents,
      who were randomly selected and aged > or = 45 years, by a survey questionnaire
      for symptoms, echocardiogram for structural abnormalities, and a 5-year follow-up
      for all-cause mortality. Unrecognized myocardial infarctions (n = 81) were
      diagnosed if ECG-based myocardial infarction (MI) criteria were met without the
      history of a documented recognized MI. RESULTS: In UMI versus no MI controls, the
      prevalence (%) of dyspnea on exertion (49 vs 29), orthopnea (6 vs 4),
      palpitations (20 vs 15), and history of fluid overload (6 vs 1) was significantly
      higher (P < .05). The associations of exertional dyspnea and history of fluid
      overload with UMI were independent of age, sex, and pulmonary disease but had a
      significant reduction in their magnitude after adjusting for global dysfunction
      (diastolic or systolic dysfunction). All the 4 symptoms were associated with
      increased risk of mortality (hazard ratios ranging from 2.3 to 9.1, P < .0001),
      which was meaningfully attenuated by adjusting for ECG-UMI status. Global
      ventricular dysfunction had a more significant impact on this association than
      regional ventricular dysfunction (wall motion abnormalities). CONCLUSIONS: The
      increased risk of mortality associated with symptoms is at least in part mediated
      via ECG-UMI. Structural abnormalities of global dysfunction play a greater role
      in mediating this risk than regional dysfunction, challenging the current
      clinical practice of calling an ECG-based MI false positive in symptomatic adults
      in the absence of wall motion abnormalities.

PMID- 16569539
TI  - Ventricular arrhythmias after acute myocardial infarction: a 20-year community
      study.
AB  - BACKGROUND: Although myocardial infarction (MI) severity is declining, the
      occurrence of ventricular arrhythmia (VA) after MI and its effect on outcome is
      unknown. This study was undertaken to examine the frequency and timing of VA and
      the effect of VA on mortality after MI. METHODS: Myocardial infarctions recorded
      between 1979 and 1998 were validated. Baseline characteristics, occurrence of VA,
      and survival were determined. Ventricular arrhythmias were categorized as primary
      ventricular fibrillation (VF), nonprimary VF, and ventricular tachycardia (VT).
      Logistic regression was used to analyze associations between VA and baseline
      characteristics. Temporal trends were assessed with the Mantel-Haenszel chi2.
      Survival was analyzed with the Kaplan-Meier method. Proportional hazards
      regression was used to examine the association between death and occurrence of
      VA. RESULTS: Among 2317 persons with incident MI, 7.5% experienced VA (3.6%
      nonprimary VF, 2.1% primary VF, 1.8% VT). Ventricular arrhythmia-associated
      factors were younger age, female sex, higher Killip class, ST elevation, and
      atrial fibrillation. Ventricular arrhythmias were associated with increased risk
      of death at 30 days. CONCLUSION: Ventricular arrhythmias after MI are relatively
      common, particularly among persons with more severe MI and no prior history of
      coronary disease. Over time, the incidence of VF declined, whereas VT did not
      change. Ventricular arrhythmia after MI was associated with a 6-fold increase in
      morality. Thus, identification of high-risk MI survivors and prevention of VA
      could markedly improve outcomes. Further studies are needed to determine the
      cause of the shift in distribution of VA subtype.

PMID- 16569540
TI  - Angina symptoms in men and women with stable coronary artery disease and evidence
      of exercise-induced myocardial perfusion defects.
AB  - BACKGROUND: To examine sex differences in pain and associated symptoms in
      patients with exercise-related ischemia, as well as the independence of these
      findings from other clinical factors. METHODS: Prospective study of 482 women and
      425 men (mean age 58 years) undergoing exercise stress testing with myocardial
      perfusion imaging (MPI). Analyses were performed on 38 women and 94 men with both
      angina and MPI evidence of ischemia during exercise. MEASURES: Chest pain
      localization, extension, intensity, quality, and presence of various non-pain
      related symptoms. RESULTS: Women rated their pain as more intense, used different
      words to describe it, and reported more non-pain-related symptoms than men (P <
      .05). They experienced pain and other sensations in the neck area more frequently
      (P < .05). Most of these differences remained after controlling for clinical or
      psychological variables, with the exception of pain intensity measures.
      CONCLUSIONS: Sex differences in the experience of symptoms associated with MPI
      evidence of myocardial ischemia may complicate timely and accurate diagnosis of
      ischemia in women.

PMID- 16569541
TI  - Prophylactic pacemaker use to allow beta-blocker therapy in patients with chronic
      heart failure with bradycardia.
AB  - BACKGROUND: Although the benefits of beta-blocker therapy for patients with
      congestive heart failure (CHF) are independent of pretreatment heart rate,
      patients with chronic systolic heart failure and low resting heart rates are
      often excluded from beta-blocker therapy. We investigated the effectiveness and
      cost-effectiveness of prophylactic pacemaker insertion to facilitate beta-blocker
      use in these patients. METHODS: A Markov model simulated the natural history of a
      cohort of clinically stable patients with CHF (ejection fraction < or = 35%, mean
      age 60 years) with resting heart rates of < 68 beat/min. Two strategies were
      evaluated: (1) conventional therapy (conventional)-the risks for death and
      hospitalization were derived from the angiotensin-converting enzyme inhibitor arm
      of the SOLVD treatment trial; and (2) pacemaker insertion with atrial pacing and
      carvedilol therapy (pacemaker-carvedilol)-risk reductions for death and CHF
      related hospitalizations for carvedilol compared with conventional therapy were
      derived from the US Carvedilol Heart Failure Study. We assumed full carvedilol
      benefits for 2 years, declining benefits for the next 3 and no additional
      benefits after 5 years, whereas pacemaker-related adverse events persisted.
      RESULTS: In the base case, the pacemaker-carvedilol strategy increased mean
      survival by 1.3 years at an incremental cost of $7800, for an incremental cost
      effectiveness of $6100 per year of life saved. Results were most sensitive to
      theoretical pacing-induced harm, changes in hospitalization cost, and reductions
      in beta-blocker benefits. CONCLUSION: Prophylactic pacemaker insertion to
      facilitate beta-blocker treatment in patients with CHF with low resting heart
      rates has the potential to produce clinical benefits in a highly cost-effective
      manner.

PMID- 16569542
TI  - Heart rate variability in patients with cardiac hypertrophy--relation to left
      ventricular mass and etiology.
AB  - BACKGROUND: Decreased heart rate variability (HRV) has been shown to reflect
      disturbances of the autonomic nervous system that is related to increased
      cardiovascular mortality. Most studies investigated HRV in patients with systolic
      left ventricular dysfunction due to remote myocardial infarction or dilated
      cardiomyopathy. To date, only few data are available on HRV in patients with
      predominant diastolic dysfunction in the presence of cardiac hypertrophy of
      different etiologies. METHODS: Time domain analysis of HRV was performed from
      digital 24-hour Holter electrocardiogram recordings in 86 patients with sinus
      rhythm and cardiac hypertrophy, which was due to aortic valve stenosis in 33
      patients, hypertrophic cardiomyopathy in 29 patients, and hypertensive heart
      disease in 24 patients. Heart rate variability analysis was compared with 91
      healthy controls. RESULTS: The SD of all normal-to-normal R-R intervals (SDNN)
      was reduced in patients with aortic valve stenosis, hypertrophic cardiomyopathy,
      and hypertensive heart disease when compared with controls (SDNN 119 +/- 42 vs
      154 +/- 36 milliseconds, P < .001). The extent of cardiac hypertrophy indexed by
      echocardiography based left ventricular mass calculation and increased patient
      age were independent predictors for depression of SDNN. CONCLUSIONS: Cardiac
      hypertrophy of various etiologies is related to decreased HRV on 24-hour Holter
      electrocardiogram. Both the patient age and the extent of left ventricular
      hypertrophy are independently associated with depression of HRV. These findings
      are independent of the cause of cardiac hypertrophy. The significance of these
      findings remains to be determined by future studies.

PMID- 16569543
TI  - Clinical predictors and timing of New York Heart Association class improvement
      with cardiac resynchronization therapy in patients with advanced chronic heart
      failure: results from the Multicenter InSync Randomized Clinical Evaluation
      (MIRACLE) and Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD)
      trials.
AB  - BACKGROUND: Based on current patient selection criteria, a significant proportion
      of recipients of cardiac resynchronization therapy (CRT) do not respond to
      treatment. The purpose of this analysis is to identify predictors and
      characterize the timing of response to CRT in patients with advanced heart
      failure. METHODS: Patients randomized to receive CRT in the MIRACLE and MIRACLE
      ICD trials, designed to assess the benefit of CRT compared with standard medical
      therapy in patients with advanced heart failure, left ventricular ejection
      fraction <0.35, and QRS > or =130 milliseconds, were included for this analysis.
      Patients with an improvement of > or =1 New York Heart Association (NYHA) class
      from baseline to the 6-month follow-up were considered responders and those who
      had no change or worse NYHA class or died were classified as nonresponders.
      Responders were subdivided into early (within 1-3 months) and late (6 months).
      RESULTS: One hundred forty-three (64%) of 224 and 190 (61%) of 313 patients in
      the MIRACLE and MIRACLE-ICD trials, respectively, responded to therapy, with 81
      (57%) of 143 and 100 (53%) of 190 responding early. Several but differing factors
      predicted CRT response and timing in the two trials with a high sensitivity (89%
      90%) but, owing to a low specificity (31%-49%), a modest predictive accuracy (66%
      75%). CONCLUSIONS: Based on improvement of > or =1 NYHA class, less than two
      thirds of patients enrolled in the MIRACLE or MIRACLE-ICD trials responded to
      CRT, with just more than half responding within the first month. Several factors
      predicted CRT response and timing, but given their modest predictive accuracy,
      comparable for both studies, additional methods for selecting candidates most
      likely to benefit from CRT are needed.

PMID- 16569544
TI  - Rapid titration of carvedilol in patients with congestive heart failure: a
      randomized trial of automated telemedicine versus frequent outpatient clinic
      visits.
AB  - BACKGROUND: Because of potential side effects and logistical difficulty of
      titrating medications, outpatients with congestive heart failure rarely receive
      appropriate doses of carvedilol or other beta-blockers. To address these
      obstacles, we studied if an automated telemedicine system named TeleWatch (TW)
      could facilitate carvedilol titration in outpatients with left ventricular
      systolic dysfunction. METHODS: Forty-nine patients with New York Heart
      Association class II and III left ventricular systolic dysfunction, who were
      tolerating appropriate afterload-reducing therapy and not receiving beta
      blockers, were enrolled into a 3-month study. Patients were randomized to have
      clinic-only (CO) (n = 24) carvedilol titration or titrations which combined
      clinic visits with TW monitoring (n = 25). All patients were seen in clinic
      biweekly, and those in the TW group were remotely monitored daily. Using a
      predefined algorithm, patients in the CO and TW groups were eligible for
      carvedilol titration on a biweekly or weekly basis, respectively, by physicians
      blinded to group assignment. RESULTS: There was no statistical difference in the
      mean final daily dose of carvedilol between the CO and TW groups (39.4 vs 36.2
      mg/d, P = .52). Because remote telemedicine titrations were as successful as
      titrations in the clinic, the time to reach the final dose of carvedilol was
      significantly shorter in the TW group (33.6 vs 63.7 days, P < .0001). There were
      5 serious adverse events in the study, 4 of which were in the TW group (P = .29);
      however, TW prospectively detected 2 adverse events. CONCLUSIONS: Remote
      monitoring with an automated telemedicine system can successfully facilitate
      titration of carvedilol in outpatients with New York Heart Association class II
      and III congestive heart failure.

PMID- 16569545
TI  - Inflammation and long-term mortality in acute congestive heart failure.
AB  - BACKGROUND: Systemic inflammation has long been recognized as a precipitator of
      acute congestive heart failure (CHF). The impact of inflammation on prognosis in
      acute CHF, however, is unknown. METHODS: This study evaluated the prognostic role
      of inflammation among 214 consecutive patients presenting with acute CHF to the
      emergency department. Patients were stratified according to C-reactive protein
      (CRP) levels determined on admission. The primary end point was all-cause
      mortality during 24-month follow-up. RESULTS: The median CRP level was 13.0 mg/L,
      with an intertertile range of 6.0 to 25.0 mg/L. Initial and long-term outcomes
      were significantly different to the detriment of patients with higher CRP levels.
      Patients in the highest CRP tertile significantly more often required admission
      to the intensive care unit (33% vs 14% in patients in the first tertile, P =
      .028) and died inhospital (15% vs 2% in patients in the first tertile, P = .027).
      Cumulative 24-month mortality rates were 33.5% in the first, 42.4% in the second,
      and 53.6% in the third tertile (P = .0265 by log-rank test). After multivariate
      adjustment, CRP remained an independent predictor of death (hazard ratio 1.4, 95%
      CI 1.1-1.8 for each step up in tertile, P = .044). CONCLUSIONS: Inflammation is a
      significant and independent predictor of long-term mortality in patients with
      acute CHF.

PMID- 16569546
TI  - A randomized, placebo-controlled, double-blind, crossover study to evaluate the
      efficacy of oral sildenafil therapy in severe pulmonary artery hypertension.
AB  - BACKGROUND: Severe pulmonary artery hypertension (PAH) is a disorder with limited
      treatment options. Recently, several newer drugs have recently been introduced to
      treat PAH. Sildenafil is one which has shown promise in several uncontrolled
      studies, but controlled trials have been few. In this randomized placebo
      controlled study, we evaluated the efficacy of oral sildenafil in idiopathic PAH
      and PAH caused by Eisenmenger syndrome. METHODS: This was a randomized, double
      blind, placebo-controlled crossover study. Twenty patients, 10 of each of
      idiopathic PAH and Eisenmenger syndrome, were randomized to receive placebo or
      sildenafil in a double-blind manner for 6 weeks and, after a washout period of 2
      weeks, were crossed over. The primary end point of efficacy was the improvement
      in distance covered in 6-minute walk test. Secondary end points were reduction in
      pulmonary artery pressure as measured by Doppler echocardiography after 6 weeks
      of treatment, improvement in clinical condition, New York Heart Association
      (NYHA) class, and exercise duration and metabolic equivalents (Mets) achieved on
      modified Bruce exercise protocol. RESULTS: There was significant improvement in
      primary and secondary end points. The primary end point of distance covered in 6
      minute walk test improved from 262 +/- 99 to 358.9 +/- 96.5 m (P < .0001) after
      treatment with sildenafil. Pulmonary artery pressure, the secondary end point,
      improved from the baseline of 98.8 +/- 20.5 to 78.3 +/- 15.3 mm Hg (P < .0001),
      NYHA class improved from 2.65 +/- 0.59 to 1.55 +/- 0.51 (P < .0001), exercise
      duration from 6.4 +/- 3.1 to 10.2 +/- 2.05 minutes (P < .0001), and Mets achieved
      from 3.32 +/- 1.57 to 6.04 +/- 1.87 (P < .0001) after treatment with sildenafil.
      There was no significant fall in blood pressure with placebo and sildenafil, and
      no serious side effects of drug were observed in the study. CONCLUSIONS:
      Sildenafil significantly improved the symptomatic status, exercise capacity, NYHA
      class, and hemodynamic parameters of patients with severe PAH and can be safely
      used as a primary or adjunctive treatment of the same.

PMID- 16569547
TI  - Prognostic value of heart rate recovery in patients with heart failure.
AB  - BACKGROUND: The rate in which heart rate recovers from exercise has recently been
      shown to be a strong predictor of mortality in patients suspected of having
      coronary disease, but its prognostic value in patients with heart failure (HF)
      has not been explored. We sought to assess the prognostic utility of heart rate
      recovery (HRR) in patients with HF. METHODS: Eighty-seven subjects diagnosed with
      compensated HF underwent cardiopulmonary exercise testing (CPX). Mean age and
      ejection fraction were 50.0 (+/-13.9) years and 28.1% (+/-13.6%), respectively.
      Heart rate at 1-minute post-CPX was subtracted from maximal heart rate during the
      exercise test to produce a measure of HRR1 in beats per minute. Subjects were
      followed for a combined death/hospitalization end point for 1-year after CPX.
      RESULTS: The mean peak respiratory exchange ratio, peak oxygen consumption (VO2),
      minute ventilation/carbon dioxide production (VE/VCO2) slope, and HRR1 were 1.06
      (+/-0.11), 14.8 (+/-4.7) mL.kg(-1).min(-1), 36.6 (+/-8.6), and 11.0 (+/-10.4)
      beat/min, respectively. Although all three variables were significant univariate
      predictors of the composite end point (P < .001), multivariate Cox regression
      analysis only retained the VE/VCO2 slope (chi2 = 33.5, P < .001) and HRR1
      (residual chi2 = 15.0, P < .001) in the equation. The hazard ratio for subjects
      having both an abnormal VE/VCO2 slope (> 34.4) and HRR1 (< 6.5 beat/min) value
      was 9.2 (95% CI 4.5-18.5, P < .0001). CONCLUSIONS: These results indicate that
      HRR provides additional prognostic information in patients with HF undergoing
      CPX. Moreover, given the independent prognostic value of HRR, this variable alone
      may provide valuable clinical information when ventilatory expired gas analysis
      is not available.

PMID- 16569548
TI  - Renal insufficiency predicts the time to first appropriate defibrillator shock.
AB  - BACKGROUND: Indications for implantable cardioverter defibrillator (ICD)
      implantation are expanding, but many primary and secondary ICD trials have
      excluded patients with advanced renal insufficiency. We investigated the effect
      of renal function on the incidence and time to first appropriate ICD shock.
      METHOD: We analyzed data from all new ICD implantations at a tertiary care center
      from July 2001 to December 2002. RESULTS: During a mean follow-up time of 445 +/-
      285 days, 29 (13%) of 230 patients (age 63 +/- 14 years, 79% men, 77% white, 75%
      coronary artery disease, left ventricular ejection fraction 0.28 +/- 0.14)
      received 41 appropriate shocks. Patients were divided into tertiles according to
      their serum creatinine level. The 1-year incidence of appropriate ICD shock was
      3.8%, 10.8%, and 22.7% in the first, second, and third tertiles, respectively (P
      = .003). Using the same cut off values of serum creatinine, the 1-year incidence
      of appropriate ICD therapy (shock and antitachycardia pacing) was 8.8%, 20.8%,
      and 26.3% (P = .02). After correcting for age, sex, race, left ventricular
      ejection fraction, indication for ICD implantation, and use of beta-blockers in a
      Cox regression model, serum creatinine was still an independent predictor of the
      time to first appropriate ICD shock (hazard ratio 6.0 for the third compared with
      the first tertile, P = .001). CONCLUSION: Renal insufficiency is a strong
      predictor of appropriate ICD shocks. Defibrillator therapy should therefore not
      be withheld based on the presence of this comorbidity. The mechanisms underlying
      the relationship between renal function and ventricular arrhythmias deserve
      further investigation.

PMID- 16569549
TI  - Intake of very long-chain n-3 fatty acids from fish and incidence of atrial
      fibrillation. The Rotterdam Study.
AB  - BACKGROUND: Atrial fibrillation is the most common sustained cardiac arrhythmia.
      It is a major cause of morbidity and mortality through an increased risk of
      thromboembolic stroke. Experimental as well as observational evidence suggests
      that n-3 polyunsaturated fatty acids may have antiarrhythmic effects. The
      objective of this study was to examine whether high intakes of fish and its very
      long-chain n-3 fatty acids eicosapentaenoic acid (EPA) plus docosahexaenoic acid
      (DHA) are associated with risk of incident atrial fibrillation. METHODS: We used
      data from the Rotterdam Study, a prospective cohort study. At baseline, dietary
      intake data were available for 5184 subjects free from atrial fibrillation.
      Dietary intake was assessed using a semiquantitative food-frequency
      questionnaire, and incidence of atrial fibrillation was continuously monitored
      during follow-up. Cox proportional hazards model (adjusted for lifestyle and
      disease factors) was used to examine the associations between intakes of EPA plus
      DHA and of fish with atrial fibrillation. RESULTS: After a mean follow-up of 6.4
      (+/-1.6) years, 312 subjects developed atrial fibrillation. Intake of EPA and DHA
      in the third textile compared with first was not associated with risk of atrial
      fibrillation (relative risk 1.18, 95% CI 0.88-1.57). Furthermore, no association
      was observed with intake of >20 g/d fish compared with no fish intake (relative
      risk 1.17, 95% CI 0.87-1.57). CONCLUSIONS: In this study, intakes of EPA and DHA
      and the consumption of fish were not associated with the onset of atrial
      fibrillation. This finding does not support that n-3 fatty acids have a general
      antiarrhythmic effect.

PMID- 16569551
TI  - Common adrenergic receptor polymorphisms as novel risk factors for vasospastic
      angina.
AB  - BACKGROUND: Sympathetic activity mediated by adrenergic receptors (ARs) appears
      to play an important role in controlling the vasomotor tone and, thus, may be
      associated with vasospastic angina (VA). We investigated the association of the
      common functional polymorphisms of the AR gene and VA. The candidates were
      alpha2CDel322-325, beta1Gly389Arg, beta2Arg16Gly, and beta2Gln27Glu
      polymorphisms. METHODS: Eighty-two patients with VA, confirmed by coronary
      angiography with or without ergonovine provocation test, and 114 apparently
      healthy control subjects were investigated for genotype of 4 AR polymorphisms and
      established risk factors of ischemic heart disease. RESULTS: The minor alleles
      were alpha2CDel322-325, beta1Gly389, beta2Gly16, and beta2Glu27 and their
      frequencies were 7%, 18%, 42%, and 29%, respectively, in the control subjects of
      this Korean population, which were different from those of other ethnic groups.
      On univariate analysis, age, smoking, male sex, alpha2CDel322-325 allele carrier
      state, and beta2Gln27 homozygote state were significant risk factors for VA.
      After multivariate analysis using multiple logistic regression model, age (odds
      ratio [OR] 1.809, CI 1.046-1.135, P < .0001), smoking (OR 4.902, CI 2.105-11.416,
      P = .0002), alpha2CDel322-325 allele carrier state (OR 5.132, CI 2.094-12.578, P
      = .0003), and beta2Gln27 allele homozygosity (OR 3.152, CI 1.364-7.285, P =
      .0072) remained as independent risk factors. In the combined genotype analysis,
      the effect of beta2Gln27 allele was evident only when the alpha2CDel322-325
      allele was absent. CONCLUSIONS: The alpha2CDel322-325 allele carrier state and
      beta2Gln27 allele homozygote state were identified as novel risk factors of VA in
      this Korean population. This result suggests the importance of the adrenergic
      stimuli and the genetic background in the pathogenesis of the VA.

PMID- 16569550
TI  - A randomized trial of prophylactic antiarrhythmic agents (amiodarone and sotalol)
      in patients with atrial fibrillation for whom direct current cardioversion is
      planned.
AB  - Antiarrhythmic agents enhance maintenance of sinus rhythm (SR) after direct
      current cardioversion (DCC) for atrial fibrillation but there are few comparative
      trials. BACKGROUND: The aims of the study were (1) to establish whether patients
      successfully cardioverted to SR are more likely to stay in SR over 6 months if
      taking amiodarone or sotalol, and if so, to establish whether one agent is better
      than the other; (2) to establish whether taking amiodarone or sotalol is better
      at achieving chemical cardioversion within the 6 weeks before DCC; and (3) to
      establish whether DCC is more likely to be successful on a drug. METHODS:
      Randomized, prospective, nonblinded, controlled study of treatment with either
      amiodarone (n = 27), sotalol (n = 36), or no antiarrhythmic agent (n = 31).
      RESULTS: Chemical cardioversion occurred in 7 patients in the amiodarone group
      (A), 7 patients in the sotalol group (S), but none in the no-antiarrhythmic group
      (N). A total of 33 (92%) patients in the sotalol group, 22 (81%) patients in the
      amiodarone group, and 23 (74%) patients in the no-antiarrhythmic group were in SR
      after cardioversion. Of the original cohort of patients, 17 (63%) patients in the
      amiodarone group remained in SR at 6-month follow-up, compared with 14 (39%) in
      the sotalol group and 5 (16%) in the no-antiarrhythmic group (A vs N, P < .0002,
      P < .0006B [after Bonferroni correction]; A vs S, P = .05, P = .15B; and S vs N,
      P = .03, P = .09B). CONCLUSIONS: Amiodarone and sotalol achieved chemical
      cardioversion before planned electrical cardioversion in 26% and 19% of patients,
      respectively. After successful cardioversion, amiodarone appears better than
      sotalol at maintaining SR at 6 months.

PMID- 16569552
TI  - Effects of lifestyle modification on the progression of coronary atherosclerosis,
      autonomic function, and angina--the role of GNB3 C825T polymorphism.
AB  - BACKGROUND: Given the multimodal medical and interventional treatment options in
      coronary artery disease, the additional value of intensified lifestyle
      modification is unclear. We have therefore examined the effects of lifestyle
      modification on top of current treatment and also associated with the GNB3 C825T
      polymorphism, which has established association to sympathetic activation and the
      precipitation of angina. METHODS: One hundred one patients with established
      coronary artery disease were randomized to a 1-year lifestyle modification group
      (lifestyle group [LG]) or an advice group. Risk factors, coronary calcification
      (electron beam tomography), heart rate variability, baroreflex sensitivity,
      anginal symptoms, and quality of life (QOL) were assessed on entry and after 1
      year. RESULTS: Patients in LG had excellent program adherence, but lifestyle
      modification had no impact on metabolic risk factors and coronary calcification.
      Changes in heart rate, heart rate variability, and blood pressure were only
      slightly favoring LG. Baroreflex sensitivity increased by 2 (0.79-3.13) ms/mm Hg
      in the LG but decreased by -0.10 (-1.11 to 0.92) in the advice group (P = .013).
      Lifestyle modification led to improved physical QOL, reductions of anginal
      attacks (-54% vs 11%, P = .01), and dose reductions in 30% of anti-ischemic
      medications (P = .004). *825T allele carriers had a more pronounced reduction of
      heart rate and improvement of angina and QOL. The beneficial effect on reduction
      of medication was seen in *825T allele carriers only. CONCLUSIONS: In the
      presence of modern treatments, comprehensive lifestyle modification provides no
      additional benefits on progression of atherosclerosis but improves autonomic
      function, angina, and QOL with concomitant reduced need of medication. These
      responses are more pronounced in GNB3*825T allele carriers.

PMID- 16569553
TI  - Single-nucleotide polymorphisms of VEGF gene are associated with risk of
      congenital valvuloseptal heart defects.
AB  - BACKGROUND: Disturbed vascular endothelial growth factor (VEGF) production during
      early heart morphogenesis causes endocardial cushion malformation, which results
      in congenital heart disease (CHD). We tested whether functional VEGF -460T/C and
      +405G/C polymorphisms that have an impact on VEGF levels were associated with
      CHD. METHODS: Dried blood samples were collected from 102 CHD children and 112
      healthy control neonates. Genotyping was done with polymerase chain reaction
      restriction fragment length polymorphism (VEGF +405G/C) and real-time polymerase
      chain reaction methods (VEGF -460T/C). RESULTS: VEGF -460C allele frequency was
      similar in control and CHD subjects. VEGF +405C allele was less prevalent in
      controls than in CHD subjects (0.21 vs 0.42, P < .001). Having VEGF +405C
      presented increased risk for CHD (odds ratio [OR] 1.72, 95% CI 1.32-2.26). VEGF 
      460CT/+405CC allele associations did not occur in controls but in CHD patients
      (0% vs 13%, OR 2.26, 95% CI 1.93-2.64), whereas -460CT/+405GG allele association
      was more prevalent in controls (32% vs 16%, OR 0.58, 95% CI 0.37-0.89).
      CONCLUSIONS: VEGF gene and allele associations may be associated with increased
      risk of CHD.

PMID- 16569554
TI  - Determining myocardial viability in chronic ischemic left ventricular
      dysfunction: a prospective comparison of rest-redistribution thallium 201 single
      photon emission computed tomography, nitroglycerin-dobutamine echocardiography,
      and intracoronary myocardial contrast echocardiography.
AB  - BACKGROUND: Detection of viable myocardium (VM) has important therapeutic
      implications for chronic ischemic left ventricular (LV) systolic dysfunction. We
      compared the ability of nitroglycerin-dobutamine echocardiography (NTG-DE),
      intracoronary myocardial contrast echocardiography (MCE), and rest-redistribution
      thallium 201 single-photon emission computed tomography (RRT-SPECT) to detect VM
      in this setting. METHODS: Patients with LV ejection fraction (LVEF) <40% and
      multivessel coronary disease suitable for revascularization underwent NTG-DE,
      MCE, RRT-SPECT, and radionuclide ventriculography to determine baseline LVEF.
      Myocardial contrast echocardiography was performed using intracoronary injection
      of Albunex. Patients who underwent revascularization had 3-month postprocedural
      radionuclide ventriculography and transthoracic echocardiography to assess
      functional recovery. RESULTS: Of 512 myocardial segments in the 32 patients
      studied, 309 were akinetic or dyskinetic at baseline. Nitroglycerin alone
      increased regional thickening in 20% of segments with contractile reserve. By RRT
      SPECT, 93% of nitroglycerin-responsive segments were viable. Myocardial contrast
      echocardiography had up to 85% sensitivity and 74% specificity for detection of
      VM diagnosed by RRT-SPECT. In the 23 patients who underwent revascularization,
      54% of akinetic segments showed improved contractility, and mean LVEF increased
      from 32% to 37% (P = .04). Sensitivities and specificities for detecting
      functional recovery were 95% and 37% for RRT-SPECT, up to 87% and 48% for MCE,
      and 63% and 83% for a biphasic response during NTG-DE. CONCLUSIONS: In patients
      with chronic ischemic LV dysfunction, RRT-SPECT had the highest sensitivity, and
      NTG-DE, the best specificity for detection of VM. Nitroglycerin facilitated
      detection of VM and may be a useful adjunct to dobutamine stimulation.

PMID- 16569556
TI  - Restrictive physiology in cardiogenic shock: observations from echocardiography.
AB  - BACKGROUND: Left ventricular diastolic abnormalities are associated with adverse
      outcome in myocardial infarction. Intra-aortic balloon pump (IABP) support is
      associated with improved diastolic filling. In the SHOCK trial and registry,
      average left ventricular ejection fraction (LVEF) was approximately 30%, higher
      than expected based on the classic paradigm. We hypothesized that restrictive
      physiology plays a role in cardiogenic shock (CS). METHODS: Echocardiograms
      obtained during the SHOCK trial within 24 hours of randomization were centrally
      interpreted. Patients with quantifiable mitral E-wave deceleration time were
      included (n = 64). The restrictive filling pattern was defined as deceleration
      time < 140 milliseconds. RESULTS: The restrictive pattern was seen in 60.9% of
      patients studied. Patients with this pattern had lower LVEF (31.1% vs 39.0%, P =
      .02) and higher wall motion score index (2.1 vs 1.8, P = .05). Patients with
      restriction were more likely to have IABP support during echocardiography (73.7%
      vs 43.5%, P = .03). There was no difference with and without restriction in
      demographic and hemodynamic variables or in mitral regurgitation degree or extent
      of coronary disease. The restrictive pattern had positive predictive value of 80%
      for pulmonary capillary wedge pressure > or = 20 mm Hg. Thirty-day survival was
      53.9% with restriction versus 68.0% without restriction, P = .31. There was no
      difference in New York Heart Association class at 1 year between groups.
      CONCLUSIONS: The restrictive filling pattern is common in patients with CS, which
      may suggest that diastolic dysfunction contributes to CS pathogenesis. Patients
      with the restrictive pattern had lower LVEF despite IABP support. An association
      between the restrictive pattern and mortality was not demonstrated; power was
      limited by sample size.

PMID- 16569555
TI  - Evaluation of a specific activity questionnaire to predict mortality in men
      referred for exercise testing.
AB  - BACKGROUND: A self-administered symptom questionnaire developed at our
      institution (Veterans Specific Activity Questionnaire [VSAQ]) is routinely used
      to estimate a patient's exercise capacity to individualize the exercise test in
      accordance with current guidelines. This study was performed to evaluate the
      association of the VSAQ with all-cause mortality. METHODS: The VSAQ was
      administered to 1185 consecutive male patients (mean age 58 +/- 12 years)
      referred for exercise testing for clinical reasons. The VSAQ is designed to
      determine which specific daily activities are associated with cardiovascular
      symptoms (fatigue, chest pain, or shortness of breath) to provide an estimate of
      exercise tolerance (in metabolic equivalents [METs]) before exercise testing.
      Patients were classified into 1 of 3 groups according to VSAQ score: <5 METs, 5
      to 8 METs, and >8 METs. The association between exercise capacity estimated by
      the VSAQ, other clinical and exercise test variables, and all-cause mortality was
      assessed by Cox proportional hazards. The mean follow-up period was 4.5 +/- 2.9
      years. RESULTS: There were a total of 132 deaths during the follow-up period,
      resulting in an average annual mortality of 2.7%. In a multivariate analysis
      including clinical risk factors and exercise test variables, age-adjusted
      predictors of mortality, in rank order, were the VSAQ score in METs, history of
      chronic heart failure, history of smoking, and diabetes (for VSAQ: hazard ratio
      [HR] 0.90, 95% CI 0.83-0.98; for chronic heart failure: HR 2.67; 95% CI 1.51
      4.72; for smoking: HR 1.74, 95% CI 1.18-2.57; and for diabetes: HR 1.84, 95% CI
      1.15-2.95). Expressed in tertiles, age-adjusted relative risks for the VSAQ were
      1.0, 0.54, and 0.22 (P for trend <.001). Each 1-MET increase in the VSAQ
      conferred a 10% survival benefit. CONCLUSIONS: A simple self-administered symptom
      questionnaire strongly and independently predicted all-cause mortality. The VSAQ
      is a useful adjunct to clinical and exercise test data for stratifying risk in
      patients undergoing exercise testing for clinical reasons.

PMID- 16569557
TI  - Elective percutaneous coronary intervention immediately impairs resting
      microvascular perfusion assessed by cardiac magnetic resonance imaging.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is known to induce
      atherosclerotic plaque rupture, which may affect resting distal microvascular
      perfusion either through distal microvascular spasm or through embolization. We
      evaluated the effect of PCI on resting microvascular flow. METHODS: We performed
      cardiovascular magnetic resonance imaging to assess left ventricular systolic
      function and microvascular perfusion in 15 patients with stable coronary artery
      disease before and within 24 hours after PCI and in 10 control subjects without
      obstructive coronary artery disease on a clinical 1.5-T CMR scanner.
      Microvascular perfusion was evaluated at rest after injecting a bolus of
      gadolinium-diethylenetriamine pentaacetic acid (0.1 mmol/kg) by calculating the
      time to 50% maximum myocardial enhancement (T50% max), as well as the relative
      upslope, of the myocardial signal intensity curve. Regional perfusion and
      systolic thickening were evaluated using a 16-segment left ventricular model with
      the slice locations matched anatomically pre-PCI and post-PCI. The relative
      contrast delay in the region of myocardium subtended by the PCI artery was
      calculated by subtracting the T50% max of a remote region from the PCI region.
      RESULTS: In subjects with coronary artery disease, PCI resulted in a regional
      contrast delay (mean delay 0.6 +/- 0.2 seconds post-PCI vs 0.0 +/- 0.2 seconds
      pre-PCI, P < .05) and a reduction in the relative upslope (8.6 +/- 0.5 post-PCI
      vs 10.1 +/- 0.7 pre-PCI, P = .02), consistent with reduced microvascular
      perfusion. This was unaccompanied by any change in regional systolic thickening
      (54% +/- 7% pre-PCI vs 53% +/- 5% post-PCI, P = NS). CONCLUSIONS: The data show
      PCI-induced impairment of resting microvascular perfusion in the area of
      myocardium subtended by the treated artery after PCI, a likely consequence of
      iatrogenic atherosclerotic plaque rupture.

PMID- 16569558
TI  - Continuous 12-lead electrocardiographic ST monitoring and long-term prognosis
      after successful coronary stenting.
AB  - BACKGROUND: The possible long-term prognostic value of transient ST ischemic
      episodes detected by continuous multilead electrocardiographic (ECG) monitoring
      after successful coronary stenting (CS) has not been thoroughly investigated.
      METHODS: A total of 739 consecutive patients, who underwent a 24-hour, continuous
      12-lead electrocardiographic (ECG) ST monitoring in the first day after
      successful CS, were studied. An ST ischemic episode was defined as a transient ST
      shift (depression or elevation) in any lead of > or = 0.10 mV compared with the
      reference ECG lasting for > or = 1 minute. RESULTS: The incidence of the
      composite of death, nonfatal myocardial infarction, and recurrent angina by the
      first year was 28.7%. Patients with > or = 3 (defined by receiver operating
      characteristics analysis) ST ischemic episodes, detected by continuous 12-lead
      ECG ST monitoring, were at significantly higher risk for the 1-year composite
      primary end point than those with either 1 and 2 (52.7% vs 25.7%, hazard ratio
      [HR] 2.1, 95% CI 1.4-3.7, P < .001) or no (52.7% vs 25%, HR 2.2, 95% CI 1.2-2.9,
      P < .001) ST ischemic episodes. By multivariate Cox regression analysis, the
      occurrence of > or = 3 ST ischemic episodes in the first postprocedural day was
      independently associated with a significant increased risk of the 1-year
      composite primary end point (HR 1.9, 95% CI 1.4-3.9, P = .002). CONCLUSIONS: The
      present study suggests that continuous 12-lead ECG ST monitoring in the first day
      after successful CS may serve as an affordable tool for the identification of
      patients with an increased risk of fatal or nonfatal ischemic complication during
      the first year after the procedure.

PMID- 16569559
TI  - Intravascular ultrasound assessment of the spatial distribution of ruptured
      coronary plaques in the left anterior descending coronary artery.
AB  - BACKGROUND: Plaque rupture is a substrate for thrombosis, occlusion, and
      myocardial infarction. The left anterior descending coronary artery (LAD)
      subtends the largest amount of myocardium; therefore, the location of LAD plaque
      rupture is of particular importance in detecting vulnerable plaques. The aim of
      our study was to assess the location of ruptured atherosclerotic plaques in the
      LAD. METHODS: Using intravascular ultrasound, we detected 160 ruptured LAD
      plaques. Of these, accurate intravascular ultrasound distance measurements (with
      consistent automatic transducer pullback [0.5 mm/s] to the LAD ostium) could be
      determined in 112 ruptured plaques. RESULTS: There were 104 patients (91 men, age
      63.8 +/- 11.7 years). The total length of the LAD that was imaged measured 48.8
      +/- 24.8 mm. The distance from the LAD origin to the maximal plaque cavity was
      16.2 +/- 10.3 mm; the maximal plaque cavity was localized to the first 20 mm of
      the LAD in 71% and the first 30 mm in 88%. Only 2 ruptured plaques were found
      beyond 40 mm from the LAD ostium. CONCLUSIONS: The majority of LAD ruptured
      plaques are located within the proximal 30 mm of the artery. This area of the LAD
      should be targeted for vulnerable (rupture-prone) plaque detection and
      prevention.

PMID- 16569560
TI  - Do operator volumes relate to clinical outcomes after percutaneous coronary
      intervention in the Canadian health care system?
AB  - BACKGROUND: Many US studies have documented an association between operator
      volume and outcomes after percutaneous coronary intervention (PCI). No study has
      assessed whether this relationship exists in Canada, where PCI is performed only
      at a limited number of regional centers and operator volumes are higher. METHODS:
      All PCI procedures performed in the province of Ontario from 1995 to 2001 were
      analyzed using administrative databases. The outcomes of interest were coronary
      artery bypass graft during the same hospitalization, mortality at 30 days, or the
      combined end point. RESULTS: A total of 38,561 PCI procedures were performed by
      65 physicians at 8 centers. Over the study period, risk-adjusted coronary artery
      bypass graft rates fell from 2.0% in 1995 to 0.7% in 2000 (P < .0001) with no
      change in mortality. The median annual PCI volume was 132 (25th, 75th percentile:
      81, 182) cases. After stratifying operators by average annual PCI volume into low
      (< 155 cases), intermediate (155-195 cases), and high (> 195 cases) volume, there
      were no significant linear relationships between risk-adjusted outcomes and
      operator terciles. No significant correlations were seen between individual PCI
      volume and risk-adjusted rates of mortality, bypass surgery, or the combined end
      point (P = .2, P = .35, and P = .95, respectively). CONCLUSIONS: In contrast to
      US studies, there does not appear to be an association between PCI volume and
      outcomes in Ontario. These findings may be related to the high annual volumes of
      most operators and institutions within Ontario.

PMID- 16569561
TI  - Cardiac procedure use following acute myocardial infarction among American
      Indians.
AB  - BACKGROUND: The prevalence of coronary heart disease is rising among American
      Indians (AIs), but there is limited evidence describing processes of care for AI
      with acute myocardial infarction (AMI). We compared rates of cardiac
      catheterization, percutaneous coronary intervention (PCI), and coronary artery
      bypass graft (CABG) surgery between AI and whites with AMI. METHODS: Using data
      from the Nationwide Inpatient Sample and the Indian Health Service National
      Patient Information Reporting System, we identified 2511 AI and 316,526 whites
      older than 30 years admitted with AMI during 1998 to 2001. Comparisons of cardiac
      procedure use between AI and whites were performed after adjusting for comorbid
      conditions and after stratifying by geographic region. RESULTS: American Indians
      were less likely than whites to undergo cardiac catheterization and PCI in 3 of 4
      geographic regions, with the largest difference occurring in the West South
      Central region (OR 0.32, 95% CI 0.24 to 0.43 for catheterization; OR 0.43, 95% CI
      0.31 to 0.57 for PCI). American Indians were less likely than whites to undergo
      CABG surgery among diabetic patients (OR 0.48, 95% CI 0.32-0.73), but not among
      nondiabetic patients (OR 0.90, 95% CI 0.72-1.12). There were no differences in
      rates of PCI and CABG surgery between AIs and whites among those receiving
      cardiac catheterization. CONCLUSIONS: Differences in the performance of coronary
      procedures are concentrated in western regions of the United States and are
      especially related to access to cardiac catheterization. Future studies are
      indicated to elucidate the mechanisms of these differences in care and their
      impact on clinical outcomes.

PMID- 16569562
TI  - Six-month outcomes after percutaneous intervention for lesions in aortocoronary
      saphenous vein grafts using distal protection devices: results from the FIRE
      trial.
AB  - BACKGROUND: The filter-based FilterWire EX (Boston Scientific, Natick, MA)
      embolic protection system and the GuardWire (Medtronic, Santa Rosa, CA) balloon
      occlusion and aspiration device have been previously shown to reduce
      periprocedural complication rates of percutaneous coronary intervention for
      saphenous vein graft (SVG) disease and are considered the standard of care in
      this setting. The late clinical course after treatment with these devices has not
      been reported. METHODS: In the FIRE trial, 651 patients undergoing SVG
      intervention were randomized to either the FilterWire EX or GuardWire. Six-month
      rates of the primary end point (composite major adverse cardiac events [MACE])
      and its components (death, myocardial infarction [MI], or target vessel
      revascularization) were studied. RESULTS: MACE at 30 days occurred in 9.9% of
      patients randomized to the FilterWire EX compared with 11.6% with the GuardWire,
      P = .53. By 6 months, MACE had increased to 19.3% and 21.9% in FilterWire EX and
      GuardWire groups, respectively, (relative risk 0.88, 95% CI 0.65-1.19; P = .44).
      All-cause 6-month mortality in the entire population was 3.5% (3.0% with
      FilterWire EX vs 4.1% with GuardWire, P = .53, with all deaths occurring after
      hospital discharge). MI occurred in 12.0% of patients at 6 months (12.1% vs 11.9%
      with the FilterWire EX and GuardWire, respectively, P = .99), and target vessel
      revascularization was required in 9.1% (8.2% vs 10.0%, respectively, P = .42).
      CONCLUSIONS: SVG intervention with the FilterWire EX and GuardWire distal
      protection devices resulted in similar outcomes at 6 months, although the
      clinical course after hospital discharge was not benign, with significant rates
      of death, MI, and repeat intervention.

PMID- 16569564
TI  - Transcatheter patent foramen ovale closure mitigates aura migraine headaches
      abolishing spontaneous right-to-left shunting.
AB  - BACKGROUND: Patent foramen ovale (PFO) has been implicated in the etiology of
      migraine headache with aura (MHA), but the mechanisms that link right-to-left (R
      to-L) shunt to MHA are unclear, and the reports on the efficacy of transcatheter
      PFO closure on MHA prevention are scarce. METHODS: We reviewed the clinical
      records of 131 consecutive patients who underwent successful transcatheter PFO
      closure at our institution at a mean age of 45 +/- 13 years because of
      cryptogenic stroke. Of the 131 patients, 35 (27%) had a diagnosis of MHA made by
      the primary care physician or the referring neurologist. Migraine headache with
      aura incidence and severity were assessed by using Migraine Disability Assessment
      (MIDAS) questionnaire. Presence and magnitude of R-to-L shunt were assessed in
      all patients by means of transesophageal echocardiography and also by means of
      transcranial Doppler (TCD) in the last 50 patients (38%). RESULTS: Patients with
      MHA had a higher prevalence of thrombophilia (P = .007), a more complex atrial
      septal anatomy (P = .001), and they also had higher prevalence of spontaneous R
      to-L shunt and of spontaneous large shunt, both at transesophageal
      echocardiography (P = .015, and .028, respectively) and at TCD (P = .036, and
      .038, respectively). After the procedure, 32 (91%) of 35 patients had either
      complete resolution or significant improvement in their MHA. At a mean follow-up
      of 1.7 +/- 1.3 years, MHA disappeared completely in 29 (83%) of 35 patients. Of
      the remaining 6 patients, 3 patients (8%) had an improvement of > or = 2 grades
      in the incidence and severity of MHA, 2 patients did not show any improvement of
      their MHA, whereas 1 patient reported a severe relapse of MHA about 1 year after
      the procedure. CONCLUSIONS: In patients with PFO, MHA is associated with
      spontaneous large R-to-L shunt and thrombophilic conditions. Transcatheter defect
      closure seems to be an effective and safe means to treat MHA in patients with
      PFO.

PMID- 16569565
TI  - Impairment of physical exercise capacity in healthy postmenopausal women.
AB  - BACKGROUND: Healthy postmenopausal women reveal a series of peripheral vascular
      abnormalities, whose possible consequences on exercise performance has not been
      yet elucidated. METHODS: We studied the response to strenuous exercise in 25
      postmenopausal women (mean age 50 +/- 3 years) without cardiovascular risk
      factors or disease through an integrative cardiopulmonary test. RESULTS: In
      comparison with 25 premenopausal subjects matched for age and biophysical
      characteristics, postmenopausal women showed a lower maximal workload (P < .01)
      and maximum VO2 (P < .01), an early anaerobic threshold (P < .05), and a lower
      ratio between increase of VO2 consumption and work rate (P < .01). CONCLUSIONS:
      Our results suggest that menopause could represent an important concomitant cause
      in determining an impairment of exercise capacity. The set of cardiopulmonary
      abnormalities found in the present study seems to identify the peripheral
      circulation as the limiting system in postmenopausal women experiencing exercise
      intolerance. Finally, present findings are in favor of an early introduction of
      postmenopausal hormone replacement therapy.

PMID- 16569563
TI  - Frequency of clinically unsuspected myocardial injury at a children's hospital.
AB  - BACKGROUND: Ill children are at risk but rarely screened for myocardial injury.
      The frequency of such injury in ill children is unknown. Elevated levels of
      plasma cardiac troponin I (cTnI) can detect subclinical myocardial injury.
      METHODS: We measured cTnI levels from 283 Children's Hospital, Boston patients
      (median age 2.10 years, range 0.13-22.4 years) seen in an outpatient or emergency
      clinic without clinically apparent cardiac disease. We took > or = 0.5 ng/mL as
      an indication of myocardial injury. We also measured plasma creatine kinase-MB,
      total creatine kinase, and myoglobin, and performed a chart review. RESULTS:
      Fifteen (7.8%) of the 193 acutely ill children and 4 (4.4%) of the 90 well
      children had an elevated cTnI level (P = .44). Within the acutely ill group, the
      children with elevated cTnI were younger and had lower mean hemoglobin and
      hematocrit levels. Cardiac troponin I levels correlated with creatine kinase-MB
      (r = 0.22; P < .001) but not with creatine kinase or myoglobin. The 4 children
      with cTnI > 0.89 ng/mL, who also had plasma cardiac troponin T measured, showed
      cardiac troponin T elevations that were consistent with unstable angina levels in
      adults. Four children had high-level cTnI elevations (> 2 ng/mL) consistent with
      acute myocardial infarction levels in adults. CONCLUSIONS: Elevated cTnI levels
      occur in children without clinically apparent cardiac disease and can be at adult
      unstable angina or acute myocardial infarction levels. Prospective studies to
      determine the clinical significance of these findings and their relationship to
      the development of cardiomyopathy are warranted.

PMID- 16569566
TI  - The extracardiac lateral tunnel Fontan, constructed with bovine pericardium:
      comparison with the extracardiac conduit Fontan.
AB  - BACKGROUND: The Fontan procedure performed with an extracardiac conduit (ECC) has
      gained wide acceptance as an alternative to the intracardiac lateral tunnel
      because it avoids placement of extensive atrial suture lines and use of
      prosthetic material in the systemic circulation. The extracardiac lateral tunnel
      (ELT) is a modification of the Fontan procedure which uses pericardium and the
      external surface of the atrium to create a conduit from the inferior vena cava to
      the pulmonary artery. This surgery theoretically avoids disruption of intra
      atrial conduction by eschewing endocardial suturing while maintaining conduit
      growth potential and the ability to easily create a fenestration to the systemic
      circulation. METHODS: We retrospectively analyzed the short-term outcome of 96
      consecutive patients who underwent an extracardiac Fontan procedure. An ELT using
      bovine pericardium was performed in 59 patients, whereas 37 patients received a
      traditional ECC. RESULTS: The 2 groups were similar with respect to age (P =
      .96), body surface area (P = .54), number of preoperative Fontan risk factors (P
      = .43), and ventricular morphology (P = .72). There were no significant
      differences in the following outcome variables between the ELT and the
      traditional ECC: length of hospitalization (P = .73), duration of chest tube
      drainage (P = .48), abnormal rhythm at time of discharge (P = .27), and mortality
      (P = .63). CONCLUSIONS: The ELT Fontan can be performed with a low risk of
      mortality and complications. The results are equivalent to the traditional ECC
      procedure. The theoretical advantages of the procedure suggest that it should be
      considered a useful modification of Fontan surgery.

PMID- 16569567
TI  - Study of the Therapeutic Effects of Intercessory Prayer (STEP) in cardiac bypass
      patients: a multicenter randomized trial of uncertainty and certainty of
      receiving intercessory prayer.
AB  - BACKGROUND: Intercessory prayer is widely believed to influence recovery from
      illness, but claims of benefits are not supported by well-controlled clinical
      trials. Prior studies have not addressed whether prayer itself or
      knowledge/certainty that prayer is being provided may influence outcome. We
      evaluated whether (1) receiving intercessory prayer or (2) being certain of
      receiving intercessory prayer was associated with uncomplicated recovery after
      coronary artery bypass graft (CABG) surgery. METHODS: Patients at 6 US hospitals
      were randomly assigned to 1 of 3 groups: 604 received intercessory prayer after
      being informed that they may or may not receive prayer; 597 did not receive
      intercessory prayer also after being informed that they may or may not receive
      prayer; and 601 received intercessory prayer after being informed they would
      receive prayer. Intercessory prayer was provided for 14 days, starting the night
      before CABG. The primary outcome was presence of any complication within 30 days
      of CABG. Secondary outcomes were any major event and mortality. RESULTS: In the 2
      groups uncertain about receiving intercessory prayer, complications occurred in
      52% (315/604) of patients who received intercessory prayer versus 51% (304/597)
      of those who did not (relative risk 1.02, 95% CI 0.92-1.15). Complications
      occurred in 59% (352/601) of patients certain of receiving intercessory prayer
      compared with the 52% (315/604) of those uncertain of receiving intercessory
      prayer (relative risk 1.14, 95% CI 1.02-1.28). Major events and 30-day mortality
      were similar across the 3 groups. CONCLUSIONS: Intercessory prayer itself had no
      effect on complication-free recovery from CABG, but certainty of receiving
      intercessory prayer was associated with a higher incidence of complications.

PMID- 16569568
TI  - Left ventricular remodeling impacts the function of the Quattro stentless mitral
      valve bioprosthesis (a 4-year experience).
AB  - OBJECTIVE: The St Jude Quattro stentless mitral valve prosthesis (QMV) is sutured
      to the mitral annulus and the papillary muscle heads, thereby preserving the
      subvalvular apparatus. After mitral valve replacement, remodeling of the left
      ventricle is often observed, causing a dilated ventricle to shrink in diameter.
      It was our objective to assess these changes in left ventricular (LV) geometry
      and evaluate its effects on the function of the QMV. METHODS: From September 1997
      to October 2000, 24 patients received QMV at our institution. The patients were
      followed up at yearly intervals (mean 4.1 +/- 2.2 years). All pre- and
      postoperative echocardiograms were evaluated, with attention focused on the
      subvalvular apparatus, leaflet morphology, and occurrence of late mitral
      regurgitation. In addition, all clinical outcomes and valve-related complications
      were recorded. RESULTS: Forty-one percent of patients (10/24) developed late
      mitral regurgitation (mild, n = 5; moderate, n = 5). The site of regurgitation
      was located at the 2 commissures in all cases. In 8 patients, changes in LV
      diameter had occurred. The point of leaflet coaptation had shifted away from the
      annulus in 4 patients. The overall mortality was 12.3%, and the postoperative
      stroke rate was 12.3%. CONCLUSIONS: Midterm changes in LV geometry seem to affect
      the competence of the QMV. Predicting these changes and subsequently adapting the
      sizing procedure remain a challenging task. The high rate of late valve
      incompetence and poor clinical outcomes has prompted us to discontinue
      recruitment of patients for this trial.

PMID- 16569569
TI  - Aptamer stationary phase for protein capture in affinity capillary
      chromatography.
AB  - The thrombin-binding DNA aptamer was used with thrombin as a model system to
      investigate protein capture using aptamer stationary phases in affinity capillary
      chromatography. The aptamer was covalently attached to the inner surface of a
      bare fused-silica glass capillary to serve as the stationary phase. Proteins were
      loaded onto the capillary via an applied pressure. The capillary was then washed
      to remove unbound and non-specifically associated proteins. Finally, the bound
      protein was released and eluted using 20 mM Tris buffer containing 8 M urea, pH
      7.3, at 50 degrees C. Eluate was collected after each step (load, wash and elute)
      and relative amounts of protein each were compared using fluorescence
      spectroscopy. The identity of the protein in the collections was confirmed using
      matrix assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass
      spectrometry. The experiment was repeated for thrombin on a bare (unmodified)
      capillary and a capillary coated with a scrambled-sequence, non-G-quartet forming
      oligonucleotide that does not bind with thrombin. The results show that the
      aptamer stationary phase captures approximately three times as much thrombin as
      the control columns. The experiment was also repeated using human serum albumin
      (HSA) alone and in an equimolar mixture with thrombin. HSA was not retained on
      the aptamer capillary, nor did it affect the capture of thrombin from the
      mixture.

PMID- 16569570
TI  - Cationic starch derivatives as dynamic coating additives for protein analysis in
      capillary electrophoresis.
AB  - Positively charged starch derivatives were used to modify the inner surface of
      fused-silica capillaries by addition to running buffer, which were subsequently
      employed in capillary electrophoresis (CE). Capillaries coated with the cationic
      starch derivatives were shown to generate a stable, reversed electroosmotic flow
      (EOF) in the investigated pH range of 3-9. The presented coating procedure was
      fast, based on a simple rinsing protocol where the polymer created a physically
      adsorbed, cationic polymer layer. Among the additives studied, a quaternary
      ammonium starch derivative showed a fast EOF mobility and effectively suppressed
      the adsorption of proteins. The intra- and inter-day reproducibility of the
      coating referring to the EOF mobility were satisfactory with relative standard
      deviation (RSD) of 0.27 and 1.67%, respectively. The coating enabled separation
      of some protein mixtures including basic proteins within l3 min with efficiencies
      up to 280,000 plates/m. In addition, this cationic starch derivative possessed a
      good solubility (about 100mg/mL), and it does not significantly contribute to the
      background adsorption in the UV region of 190-400 nm.

PMID- 16569571
TI  - Capillary electrophoretic competitive immunoassay with laser-induced fluorescence
      detection for methionine-enkephalin.
AB  - Immunoassays are commonly used in bioresearch for the detection and
      quantification of small proteins and macromolecules in biological fluids and
      other complex matrices. In this report, a competitive immunoassay using capillary
      electrophoresis (CE) with laser-induced fluorescence was developed for methionine
      enkephalin (ME). The method is based on the competitive reaction between the ME
      and fluorescein conjugated ME (ME-F) with anti-ME antibody, capillary
      electrophoresis separation of the ME-antibody bound and free ME-F, followed by
      the laser-induced fluorescence detection of the fluorescent species. With the
      optimized separation conditions, it was possible to separate the antibody bound
      and free fluorescien conjugated ME by a capillary electrophoresis-laser-induced
      fluorescence (CE-LIF) analysis using an uncoated fused-silica capillaries. The
      results concluded that the assay specificity, selectivity and accuracy were
      excellent.

PMID- 16569572
TI  - Separation of 3'-azido-2',3'-dideoxythymidine pronucleotide diastereoisomers in
      biological samples by CZE with cyclodextrin addition.
AB  - The possibility of using capillary electrophoresis as an alternative technique to
      HPLC for the separation of pronucleotide diastereoisomers of AZT was
      investigated. In the pH range 6.2-7.2 where the analytes are stable, a chiral
      additive, carboxymethyl-beta-CD, was found appropriate to enable the separation
      of the uncharged diastereoisomers. An experimental design strategy was used to
      study the influence of several parameters (CD and phosphate buffer concentration,
      methanol content of the electrolyte, injected volume, capillary length, electric
      field and separation temperature) on the separation and find suitable analytical
      conditions for monitoring the prodrugs in cell extracts. The diastereoisomers of
      the three tBuSATE phenylphosphotriester derivatives of AZT studied could be fully
      resolved within short analysis time (less than 10 min). Method validation results
      showed satisfactory results for linearity, accuracy and repeatability.

PMID- 16569573
TI  - Separation and detection of peroxynitrite and its metabolites by capillary
      electrophoresis with UV detection.
AB  - A method for the separation and direct detection of peroxynitrite (ONOO(-)) and
      two of its degradation products, nitrite (NO(2)(-)) and nitrate (NO(3)(-)), using
      capillary electrophoresis with ultraviolet detection is described. The separation
      parameters were optimized and included electrokinetic injection, a run buffer
      consisting of 25 mM K(2)HPO(4) 7.5 mM DTAB, pH 12, and a field strength of -323
      V/cm. A diode array UV detector was employed in these studies as it allowed the
      determination of all three species simultaneously. Nitrate and nitrite provided
      the maximum response at 214 nm while peroxynitrite generated the best response at
      302 nm. All three species could be detected at 214 nm, while simultaneous
      detection at 214 and 302 nm positively identified each peak.

PMID- 16569574
TI  - Quantitation of nicotinamide and serotonin derivatives and detection of flavins
      in neuronal extracts using capillary electrophoresis with multiphoton-excited
      fluorescence.
AB  - Capillary electrophoresis (CE) with multiphoton-excited fluorescence detection
      (CE-MPE) allows low-background analysis of spectrally distinct fluorophores using
      a single long-wavelength laser. Extracts were prepared from immortalized rat
      raphe nuclei neurons, and were analyzed by CE-MPE. Native fluorescence was
      detected from reduced nicotinamide adenine dinucleotide (NADH) and its
      phosphorylated form (NADPH), flavin adenine dinucleotide (FAD), flavin
      mononucleotide (FMN), riboflavin, serotonin, and 5-hydroxytryptophan (5HTrp).
      Quantitation of exogenous serotonin (taken up by cells) and endogenous NADH and
      5HTrp was possible using internal standards or standard addition. This system
      should be useful to study monamine oxidase inhibitors (MAOIs) and selective
      serotonin reuptake inhibitors (SSRIs).

PMID- 16569575
TI  - On-line preconcentration and determination of ketamine and norketamine by
      micellar electrokinetic chromatography. Complementary method to gas
      chromatography/mass spectrometry.
AB  - We have investigated a rapid, simple, and highly efficient on-line
      preconcentration method using in micellar electrokinetic chromatography (MEKC)
      for the analysis of abused drugs. Ketamine is an anesthetic that has been abused
      as a hallucinogen. We applied the sample sweeping technique first to ketamine and
      its major metabolite, norketamine, and separated the analytes with MEKC. Several
      of the sweeping MEKC parameters to effect successful separations, such as the
      concentration of sodium dodecyl sulfate (SDS), the injection time, and the
      applied voltage were optimized. The improvements in the number of theoretical
      plates under the different separation conditions are presented clearly in a three
      dimensional representation. The limits of detection were 2.8, 3.4, and 3.3 ng/mL
      for ketamine, norketamine, and ketamine-D(4), respectively. The enrichment factor
      for each compound was within the range of 540-800. Experimental results are in
      agreement with those of analysis conducted by gas chromatography/mass
      spectroscopy (GC/MS). Therefore, we believe that sweeping, combined with MEKC,
      represents a suitable complementary method to GC/MS for use in clinical and
      forensic analyses of ketamine and norketamine.

PMID- 16569576
TI  - Proteomic profiling of human urine using multi-dimensional protein identification
      technology.
AB  - Human urine samples are ideal for proteomic profiling and have tremendous
      potential as sources of biomarkers. Multi-dimensional protein identification
      technology (MudPIT) is an effective approach to analyzing human urine or other
      fluids dominated by diverse metabolites. MudPIT analysis was used to identify 87
      proteins in just 15 ml of human urine. A high throughput, reproducible, and
      sensitive technology, MudPIT may soon be used for more proteomic analyses of
      metabolites.

PMID- 16569577
TI  - Exploring human plasma proteome strategies: high efficiency in-solution digestion
      protocol for multi-dimensional protein identification technology.
AB  - Multi-dimensional protein identification technology (MudPIT) is becoming a
      prevalent proteomic approach due to its high-throughput separations and accurate
      mass detection. Prior to MudPIT analysis, complicated samples required in
      solution digestion. Unlike in-gel digestion, in which enzymes work on just a few
      proteins, in-solution digestion involves simultaneous digestion of hundreds or
      thousands of proteins. In-solution digestion protocols must therefore be very
      efficient. Few investigations have evaluated the efficiency of in-solution
      digestion protocols. The present research compared three such protocols. Results
      suggest that a protocol utilizing trifluoroethanol (TFE) as denaturant is most
      efficient.

PMID- 16569578
TI  - Ion-interaction-capillary zone electrophoresis of cationic proteomic peptide
      standards.
AB  - We have employed a novel capillary electrophoresis (CE) approach recently
      developed in our laboratory, termed ion-interaction-capillary zone
      electrophoresis (II-CZE), to the resolution of a mixture of 27 synthetic cationic
      proteomic peptide standards. These peptides were comprised of three groups of
      nine peptides (with net charges of +1, +2 and +3 for all nine peptides within a
      group), the hydrophobicity of the nine peptides within a group varying only
      subtly between adjacent peptides. This bidimensional CE approach achieved
      excellent resolution of the peptides with high peak capacity by combining the
      powerful CZE mechanism located in the background electrolyte (BGE) with an
      hydrophobicity-based mechanism also located in the BGE, the latter consisting of
      high concentrations (up to 0.4M) of aqueous perfluorinated acids (trifluoroacetic
      acid, pentafluoropropionic acid and heptafluorobutyric acid). Thus, concomitant
      with a CZE separation of the three differently charged groups of peptides, there
      is an hydrophobically-mediated separation of the peptides within these groups
      effected through interaction of the hydrophobic anions of the perfluorinated
      acids with hydrophobic amino acid side-chains in the peptides. This methodology
      is dramatically different from other CE methods that have used complexing agents
      such as micelles or cyclodextrins in MEKC. Overall, the results presented here
      demonstrate the value of CE as a peptide separative tool in its own right,
      including its use for proteomic applications, and not merely as a complementary
      technique to reversed-phase high-performance liquid chromatography (RP-HPLC).

PMID- 16569579
TI  - Microdevice DNA forensics by the simple tandem repeat method.
AB  - We review recent experiments on DNA forensics by the simple tandem repeat (STR)
      method using a 16-lane micromachined device as the active separation element.
      Separations by linear polyacrylamide matrices show very high data quality metrics
      when evaluated with statistically significant data sets. Full 16-locus
      multiplexes are verified on the multilane system. Multi-donor mixed samples are
      studied in the context of the limits of the laser-induced fluorescence detector
      and data-reduction software. The microdevice appears to be posed to outperform
      current capillary arrays in terms of stability and, through specialized sample
      loading, in the interpretation of complex mixtures.

PMID- 16569580
TI  - Development and characterization of on-chip biopolymer membranes.
AB  - In lab-on-a-chip applications, filtration is currently performed prior to sample
      loading or through pre-cast membranes adhered to the substrate. These membranes
      cannot be patterned to micrometer resolution, and their adhesion may be
      incompatible with the fabrication process or may introduce contaminants. We have
      developed an on-chip separation process using a biocompatible polymer that can be
      patterned and has controllable molecular rejection properties. We spun cast
      cellulose acetate (CA) membranes directly onto silicon wafers. Characterization
      of the molecular flux across the membrane showed that molecular weight and charge
      are major factors contributing to the membranes' rejection characteristics.
      Altering casting conditions such as polymer concentration in the casting solution
      and the quenching-bath composition and/or temperature allowed control of the
      molecular weight cut-off (MWCO). Three MWCOs; 300, 350, and 700 Da have been
      achieved for non-linear molecules. Molecular shape is also very important as much
      higher molecular weight single-stranded DNA was electrophoresed across the
      membranes while heme with a similar negative charge density was rejected. This
      was due to DNA's small molecular cross section. This is an important result
      because heme inhibits polymerase chain reactions (PCR) reducing the detection and
      characterization of DNA from blood samples.

PMID- 16569581
TI  - Monitoring erythrocytes in a microchip channel that narrows uniformly: towards an
      improved microfluidic-based mimic of the microcirculation.
AB  - The release of adenosine triphosphate (ATP) from red blood cells (RBCs) flowing
      through PDMS microchannels has been determined as a function of channel cross
      sectional area using a design containing a channel that narrows uniformly. ATP,
      released from the RBCs in response to the mechanical deformation of their cell
      membranes, increased as the channel cross-section decreased. One sample of rabbit
      RBCs released 1.16 +/- 0.11, 1.92 +/- 0.14 and 2.09 +/- 0.10 microM ATP as the
      median cross-sectional area decreased from 4314 to 3192 to 2052 microm(2),
      respectively. Numerous samples (n = 6) displayed the same trend. Incubating a
      sample of RBCs with diamide, a substance known to stiffen cell membranes without
      harming the cell cytosol, provided evidence that no cell lysis occurred in the
      microchip device. This novel use of lab-on-a-chip technology allows for channel
      designs that enable an in vitro study of physiological events that occur in the
      microcirculation.

PMID- 16569582
TI  - Monitoring of intercellular messengers released from neuron networks cultured in
      a microchip.
AB  - A cellular biochemistry analysis system was integrated on a quartz glass
      microchip with a microchamber for cell culture followed by a microchannel for
      detecting with a thermal lens microscope (TLM). Nerve cells from rat hippocampus
      were successfully cultured to form neural networks in the microchip. An aqueous
      solution of glutamate, which is known as a neurotransmitter, was introduced to
      stimulate the cultured neuron to release a retrograde messenger, arachidonate
      which is considered to be critical for neuronal plasticity, especially for long
      term potentiation (LTP). After the introduction, the solution that flowed through
      the culture chamber was analyzed using the UV-TLM (excitation wavelength, 244
      nm). The measured signal intensity was dependent on glutamate solution
      concentration, and the neurons were considered to release the retrograde
      messenger according to the glutamate concentration. This system is suitable for
      time-course monitoring of ultra trace amounts of chemicals released from very
      small amount of cultured cells.

PMID- 16569583
TI  - Cell culture and life support system for microbioreactor and bioassay.
AB  - A microchip-based cell culture system was developed and a primary culture of rat
      hepatocytes was realized in the system. The microchip was made of glass plates
      and had a microchannel and a microculture flask inside. The flask inner surface
      was coated using collagen solution; then FBS and DMEM were added successively.
      Rat hepatocytes suspended in a medium was introduced into the microchip and
      incubated at 37 degrees C in a humidified atmosphere with 5% CO(2). Because of
      the shortage of dissolved oxygen, the cultured cells in the microchip resulted in
      a significant decrease in viability. To overcome this, a continuous medium flow
      oxygen and nutrition supplying system was designed and constructed. The system
      realized good cell growth for at least 4 days. Liver-specific functions, such as
      the synthesis of albumin and urea from hepatocytes were confirmed.

PMID- 16569584
TI  - Physiochemical properties of various polymer substrates and their effects on
      microchip electrophoresis performance.
AB  - A suite of polymers were evaluated for their suitability as viable substrate
      materials for microchip electrophoresis applications, which were fabricated via
      replication technology. The relevant physiochemical properties investigated
      included the glass transition temperature (T(g)), UV-vis absorption properties,
      autofluorescence levels, electroosmotic flow (EOF) and
      hydrophobicity/hydrophilicity as determined by sessile water contact angle
      measurements. These physiochemical properties were used as a guide to select the
      proper substrate material for the intended microchip electrophoretic application.
      The T(g) of these polymers provided a guide for optimizing embossing parameters
      to minimize replication errors (REs), which were evaluated from surface
      profilometer traces. RE values ranged from 0.4 to 13.6% for the polymers
      polycarbonate (PC) and low-density polyethylene (LDPE), respectively. The
      absorption spectra and autofluorescence levels of the polymers were also measured
      at several different wavelengths. In terms of optical clarity (low absorption
      losses and small autofluorescence levels), poly(methyl methacrylate), PMMA (clear
      acrylic), provided ideal characteristics with autofluorescence levels comparable
      to glass at excitation wavelengths that ranged from 488-780 nm. Contact angle
      measurements showed a maximum (i.e., high degree of hydrophobicity) for
      polypropylene (PP), with an average contact angle of 104 degrees +/-3 degrees and
      a minimum exhibited by gray acrylic, G-PMMA, with an average contact angle of 27
      degrees +/-2 degrees. The EOF was also measured for thermally assembled chips
      both before and after treatment with bovine serum albumin (BSA). The
      electrophoretic separation of a mixture of dye-labeled proteins including;
      carbonic anhydrase, phosphorylase B, beta-galactosidase, and myosin, was
      performed on four different polymer microchips using laser-induced fluorescence
      (LIF) excitation at 632.8 nm. A maximum average resolution of 5.04 for several
      peak pairs was found with an efficiency of 6.68 x 10(4) plates for myosin
      obtained using a BSA-treated PETG microchip.

PMID- 16569585
TI  - On-chip temperature gradient interaction chromatography.
AB  - This paper reports the first integrated microelectromechanical system (MEMS) HPLC
      chip that consists of a parylene high-pressure LC column, an electrochemical
      sensor, a resistive heater and a thermal-isolation structure for on-chip
      temperature gradient interaction chromatography application. The separation
      column was 8 mm long, 100 microm wide, 25 microm high and was packed with 5
      microm sized, C18-coated beads using conventional slurry-packing technique. A
      novel parylene-enhanced, air-gap thermal isolation technology was used to reduce
      heater power consumption by 58% and to reduce temperature rise in the off-column
      area by 67%. The fabricated chip consumed 400 mW when operated at 100 degrees C.
      To test the chromatography performance of the fabricated system, a mixture of
      derivatized amino acids was chosen for separation. A temporal temperature
      gradient scanning from 25 to 65 degrees C with a ramping rate of 3.6 degrees
      C/min was applied to the column during separation. Successful chromatographic
      separation of derivatized amino acids was carried out using our chip. Compared
      with conventional temperature gradient HPLC system which incorporates "macro
      oven" to generate temporal temperature gradient on the column, our chip's thermal
      performance, i.e., power consumption and thermal response, is greatly improved
      without sacrificing chromatography quality.

PMID- 16569586
TI  - Epstein-Barr virus, cytokines, and inflammation: a cocktail for the pathogenesis
      of Hodgkin's lymphoma?
AB  - The association between chronic inflammation and cancer has been known for well
      over a century. However, direct evidence detailing the role of inflammation in
      carcinogenesis has been slow in forthcoming. A number of recent studies suggest
      that the gaps in our understanding of the molecular pathways bridging the link
      between inflammation and cancer are slowly beginning to close and that this
      relationship is more deep-rooted than had been previously believed. This review
      addresses the link between inflammation and Hodgkin's lymphoma (HL), a malignancy
      which has many features reminiscent of chronic inflammation. The role of Epstein
      Barr virus (EBV) in the pathogenesis of HL is discussed, along with an outline of
      our current understanding of the cellular nature and development of Reed
      Sternberg cells, the malignant cells of HL. The involvement of cytokines and
      chemokines as orchestrators of inflammation and vehicles for chemical cross-talk
      between the malignant cells and the reactive inflammatory infiltrate forms a
      major part of the review. It is suggested that chronic inflammation, triggered by
      factors such as EBV, is likely to contribute to tumor cell proliferation,
      progression, and inhibition of apoptosis. Furthermore, it is proposed that the
      pro-inflammatory transcription factor NF-kappaB plays a central role in many of
      these processes.

PMID- 16569587
TI  - Granulocyte function is stimulated by a novel hexapeptide, WKYMVm, in
      chemotherapy-treated cancer patients.
AB  - Bacterial infections are major life-threatening complications in patients
      receiving cytotoxic drugs. These infections generally occur during periods of
      neutropenia. It has been suggested that the incidence of neutropenia correlates
      with the incidence of infections. A synthetic hexapeptide, WKYMVm, which
      stimulates phosphoinositide hydrolysis in leukocytes, has been shown to activate
      microbicidal activities of human polymorphonuclear neutrophils. In this study, we
      evaluate whether WKYMVm stimulates bactericidal activity in neutrophils obtained
      from patients who received chemotherapy for solid tumors when they were
      neutropenic. Eight patients and 11 healthy controls were recruited for the study.
      Patient neutrophils, on day 0 and at 2 weeks after chemotherapy, were collected.
      Expression of the WKYMVm peptide receptor, on leukocytes, was analyzed by
      fluorescein-activated cell sorting. Neutrophil bactericidal assays were performed
      using both reactive oxygen species generation and intracellular killing.
      Expression of the WKYMVm peptide receptor on leukocytes showed no difference in
      the treated patients compared to healthy controls. WKYMVm increased bactericidal
      activities, in a dose-dependent fashion, of control neutrophils compared to
      treated patient neutrophils obtained on day 0. WKYMVm markedly stimulated
      bactericidal activity of treated patient neutrophils obtained at 2 weeks after
      chemotherapy compared to treated patient neutrophils obtained on day 0. WKYMVm
      augmented neutrophil bactericidal activity was noted at low concentration but was
      suppressed at higher concentrations of 5-fluorouracil. WKYMVm augmented
      neutrophil bactericidal activity was not suppressed by cisplatin. WKYMVm has the
      potential for increasing neutrophil bactericidal activity in chemotherapy-treated
      cancer patients.

PMID- 16569588
TI  - Induction of HSP70 is dispensable for anti-inflammatory action of heat shock or
      NSAIDs in mast cells.
AB  - OBJECTIVE: It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs),
      such as acetylsalicylic acid, ibuprofen, and indomethacin, induce anti
      inflammatory effects through inhibition of cyclooxygenase enzyme activity.
      However, it has also been established that a variety of their anti-inflammatory
      effects are independent of cyclooxygenase. In the search for alternative modes of
      action, it was found that NSAIDs share some cellular effects with heat shock
      treatment. This prompted us to investigate whether NSAIDs modulate production of
      proinflammatory cytokines by mast cells through the heat shock response.
      MATERIALS AND METHODS: In mouse mast cells, derived from a culture of bone marrow
      cells of male BALB/cBy and null HSF-1(-/-) mice, responsiveness to heat shock and
      NSAIDs was monitored by measuring tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) production and signaling pathways. RESULTS: In bone marrow
      derived mast cells (BMMC), we found that heat shock and a number of NSAIDs
      induced heat shock protein 70 (HSP70), which was closely paralleled with
      inhibition of IL-6 and TNF-alpha production. Surprisingly, in BMMC from HSF-1(-/
      )mice, heat shock and selected NSAIDs were still able to suppress cytokine
      production in the absence of HSP70 induction. CONCLUSION: In this article, we
      provide evidence that inhibition of release of proinflammatory cytokines by
      NSAIDs and heat shock may be attributed to inhibition of the inhibitory nuclear
      factor kappaB (NF-kappaB) kinase activity, extracellular signal-regulated kinases
      1/2, and p38 pathways, resulting in decreased transcriptional activity of the NF
      kappaB pathway.

PMID- 16569589
TI  - Delta-4 Notch ligand promotes erythroid differentiation of human umbilical cord
      blood CD34+ cells.
AB  - OBJECTIVE: Important roles of Notch signaling have been demonstrated in
      hematopoiesis. In many cases, activation of the Notch pathway leads to the
      inhibition of differentiation of immature precursors, suggesting a potential role
      in self-renewal promotion. However, the function of Notch and Notch ligands is
      not so straightforward because it is considerably dependent on cytokine context.
      In this study, we analyzed effects of one Notch ligand, Delta-4, whose function
      is less clear than others, such as Delta-1 and Jagged-1 and -2. METHODS: CD34(+)
      cells isolated from human umbilical cord blood were cocultured with a Delta-4
      expressing murine stromal cell line, SC9-19, and induced to erythroid
      differentiation by adding stem cell factor and erythropoietin. To examine the
      involvement of Delta-4, we utilized stromal cell subclones expressing Delta-4
      protein at higher or lower level than parental SC9-19 by plasmid transfection.
      Erythroid maturation was examined by surface phenotype (CD34 and glycophorin A)
      and cytospin morphology. Recombinant human Delta-4 protein was prepared to
      analyze direct effects of Delta-4. RESULTS: Under erythroid lineage-inducing
      conditions, we found that the increase in Delta-4 expression of SC9-19 promoted
      erythroid differentiation whereas the decrease in Delta-4 expression inhibited
      it. Morphologic examination as well as colony formation analysis supported this
      observation. Moreover, the experiment using recombinant Delta-4 provided direct
      evidence of the Delta-4 activity found in coculture system. CONCLUSIONS: By
      modifying Delta-4 expression of the stromal cells and using the recombinant
      protein, we demonstrated that Delta-4 had a differentiation promoting activity
      for human primitive hematopoietic cells into erythroid lineage.

PMID- 16569590
TI  - Decreased homing of retrovirally transduced human bone marrow CD34+ cells in the
      NOD/SCID mouse model.
AB  - OBJECTIVE: Many clinical gene therapy trials have described poor engraftment of
      retrovirally transduced CD34(+) cells. Because engraftment is dependent upon
      successful homing of graft cells to the bone marrow (BM), we examined whether
      retroviral-mediated gene transfer (RMGT) induces a homing defect in CD34(+)
      cells. METHODS: Homing of fluorescently labeled human BM CD34(+) cells transduced
      with three separate retroviral vectors (MFG-eGFP, LNC-eGFP, and LXSN) was
      assessed in nonobese diabetic/severe combined immunodeficient mice. RESULTS:
      Homing of transduced CD34(+) cells was significantly decreased 20 hours after
      transplantation compared with freshly isolated control and cultured untransduced
      control cells. Specifically, homing of GFP(+) cells in the graft was
      preferentially decreased thus skewing the contribution of transduced cells to
      engraftment. Transduced cells were not selectively trapped in other organs and BM
      homed transduced cells did not undergo apoptosis at a higher rate than
      untransduced cells. Adhesion molecule expression and binding activity was not
      altered by RMGT. This homing defect was reversed when transduced cells were
      cultured over CH-296 for 2 additional days with SCF only. CONCLUSION: These data
      suggest that RMGT of hematopoietic cells may compromise their homing potential
      and implicate transduction-induced reduced homing in the observed low engraftment
      of retrovirally transduced CD34(+) cells. These results may have a direct
      clinical application in gene therapy protocols.

PMID- 16569591
TI  - Novel ligands for cancer diagnosis: selection of peptide ligands for
      identification and isolation of B-cell lymphomas.
AB  - OBJECTIVE: Lymphoma and leukemia account for nearly 8% of cancer fatalities each
      year. Present treatments do not differentiate between normal and malignant cells.
      New reagents that distinguish malignant cells and enable the isolation of these
      cells from the normal background will enhance the molecular characterization of
      disease and specificity of treatment. METHODS: Peptide ligands were selected from
      a phage-displayed peptide library by biopanning on the B-cell lymphoma line, A20.
      The isolated peptides were assessed as reagents for identification and isolation
      of lymphoma cells by flow cytometry and cell capture with magnetic beads.
      RESULTS: Two novel peptides and one obtained previously on cardiomyocytes were
      selected. A20 cells bind phage displaying these peptides 250- to 450-fold over
      control phage. These phage bind to other bone marrow-derived cancel lines
      including some macrophage and T cells but do not bind to normal splenocytes.
      Synthetic constructs of these peptides have binding affinities comparable to B
      cell-specific antibodies. Similar to antibodies, these peptides can be used in
      flow cytometry and magnetic bead capture to distinguish lymphoma cells from
      normal splenocytes. CONCLUSION: Bone marrow-derived malignant cells express cell
      surface markers that can be used to distinguish them from normal cells. These
      results demonstrate the ability to use an unbiased screen to rapidly generate
      high-affinity peptide ligands for identification and isolation of lymphoma cells.

PMID- 16569592
TI  - Epigenetic heterochromatin markers distinguish terminally differentiated
      leukocytes from incompletely differentiated leukemia cells in human blood.
AB  - OBJECTIVE: During terminal cell differentiation, nuclear chromatin becomes
      condensed and the repertoire of epigentic heterochromatin proteins responsible
      for chromatin condensation is dramatically changed. In order to identify the
      chromatin regulatory factors associated with incomplete cell differentiation and
      impaired chromatin condensation in hematological malignancies, we examined
      expression levels of major heterochromatin proteins in normal blood cells and
      cells derived from a number of chronic and acute myeloid leukemia patients
      exhibiting different degrees of differentiation. METHODS: We used immunoblotting
      and immunofluorescence to examine the levels and localization of epigenetic
      heterochromatin factors in isolated cell nuclei and fractionated peripheral blood
      cells. RESULTS: While the major epigenetic heterochromatin factor, histone H3
      methylated at lysine 9, is present in all cell types, its main counterparts,
      nonhistone proteins, heterochromatin proteins 1 (HP1) alpha, beta, and gamma, are
      dramatically reduced in peripheral blood leukocytes of normal donors and chronic
      myeloid leukemia patients, but are substantially increased in the blood of
      accelerated phase and blast crisis patients. In the terminally differentiated
      cells, nuclear chromatin accumulates a nucleocytoplasmic serpin, monocyte and
      neutrophil elastase inhibitor (MNEI). HP1 and MNEI levels inversely correlate in
      a number of normal and leukemia myeloid cells and show strikingly opposite
      coordinated changes during differentiation of U937 cell line induced by retinoic
      acid. CONCLUSIONS: Our results suggest that repression of HP1 and accumulation of
      MNEI are linked to terminal cell differentiation and that their levels may be
      monitored in blood cell populations to detect transitions in cell differentiation
      associated with leukemia progression and treatment.

PMID- 16569593
TI  - Cellular foundation of curcumin-induced apoptosis in follicular lymphoma cell
      lines.
AB  - OBJECTIVE: Although responsive to first-line treatments, follicular lymphoma (FL)
      remains a fatal disease of increasing worldwide incidence. In efforts to find
      novel approaches to inhibit proliferation and induce apoptosis in FL cells, we
      examined the action of naturally occurring compound curcumin in the three
      recently established FL cell lines. MATERIALS AND METHODS: Cytotoxic effects and
      determination of apoptotic attributes upon curcumin treatment were analyzed using
      growth inhibition, [(3)H]-thymidine, fluorescence microscopy, and flow cytometry
      assays, as well as Western blotting. Chemical inhibitor studies for the
      assessment of caspase and cathepsin contribution were applied. Expression of 10
      members of the bcl-2 family proteins was evaluated by immunoblotting. RESULTS:
      Curcumin inhibited proliferation and growth, and induced profound apoptosis
      associated with a shift in the balance of the bcl-2 family proteins, in all cell
      lines tested. Strikingly, we observed that curcumin-induced caspase-dependent
      apoptosis is also associated with lysosomal rupture (LMP). An increase in
      intracellular ROS generation appeared critical for curcumin-evoked LMP, loss of
      Deltapsi(m,) caspase activation, and cell death, as well as ascorbic acid
      mediated enhancement of curcumin's action. CONCLUSION: We have demonstrated for
      the first time that curcumin is an efficient inducer of apoptosis in FL cell
      lines, meriting its further evaluation in vivo.

PMID- 16569594
TI  - Clinical grade expansion of CD45RA, CD45RO, and CD62L-positive T-cell lines from
      HLA-compatible donors: high cytotoxic potential against AML and ALL cells.
AB  - OBJECTIVE: Identification of a clinical grade method for the ex vivo generation
      of donor-derived T cells cytotoxic against both myeloid and lymphoblastic cells
      still remains elusive. We investigated rapid generation and expansion of donor
      derived-allogeneic T-cell lines cytotoxic against patient leukemic cells.
      MATERIALS AND METHODS: Acute myelogenous leukemia (AML) and acute lymphoblastic
      leukemia (ALL) blasts were cultured 5 days in Stem Span, granulocyte macrophage
      colony-stimulating factor, interleukin-4, and calcium ionophore. All B-precursor
      ALL (N22) and AML (N13), but not T-cell ALL (N3), differentiated into mature
      leukemia-derived antigen-presenting cells (LD-APC). All but one LD-APC generated
      cytotoxic T lymphocyte (CTL) from adult human leukocyte antigen (HLA)-identical
      (N8) or unrelated donors (N2). RESULTS: Upon in vitro culture, donor-derived CTL
      acquired a memory T phenotype, showing concomitant high CD45RA, CD45RO, CD62L
      expression. CD8(+) cells, but not CD4(+) cells, were granzyme, perforine, and
      interferon-gamma-positive. Pooled CD4(+) and CD8(+) cells were cytotoxic against
      leukemic blasts (32%, 30:1 E:T ratio), but not against autologous or patient
      derived phytohemagglutinin blasts. LD-APC from five ALL patients were used to
      generate CTL from cord blood. A mixed population of CD4(+) and CD8(+) cells was
      documented in 54% of wells. T cells acquired classical effector memory phenotype
      and showed a higher cytotoxicity against leukemia blasts (47%, 1:1 E:T ratio).
      Adult and cord blood CTL showed a skewing from a complete T-cell receptor
      repertoire to an oligo-clonal/clonal pattern. CONCLUSIONS: Availability of these
      cells should allow clinical trials for salvage treatment of leukemia patients
      relapsing after allogeneic stem cell transplantation.

PMID- 16569595
TI  - Identification of a new HLA-A2-restricted T-cell epitope within HM1.24 as
      immunotherapy target for multiple myeloma.
AB  - OBJECTIVE: The aim of this study was identification of human leukocyte antigen
      (HLA)-A2-restricted T-cell epitopes within the HM1.24 antigen as target for
      multiple myeloma (MM)-directed specific peptide-based immunotherapy. METHODS: The
      HM1.24 sequence was scanned for immunogenic peptides using the HLA-binding
      prediction software SYFPEITHI and BIMAS. Peripheral blood mononuclear cells from
      HLA-A2(+) healthy volunteers/blood donors (ND) were stimulated with autologous
      HM1.24-peptide-loaded dendritic cells, and expanded in vitro. Activation of T
      cells was assessed by ELISpot and cytotoxicity by (51)Chromium ((51)Cr)-release
      assays. T2-cells pulsed with irrelevant peptide, the HM1.24(-)/HLA-A2(+) breast
      carcinoma cell line MCF-7 and the HM1.24(+)/HLA-A2(-) myeloma cell line RPMI-8226
      were used as controls. Expression of the HM1.24 gene (BST2) was assessed using
      purified plasma cells and Affymetrix-U133A+B microarrays. Frequency of peptide
      specific CD8(+) T cells was detected using the flow-cytometric tetramer
      technique. RESULTS: Of eight nona-peptides with the highest probability of
      binding to HLA-A2, the HM1.24 aa22-30 peptide (LLLGIGILV) showed the most
      frequent activation of CD8(+) T cells in healthy volunteers (specific activation
      in 8 of 11 [73%] ND; compared with 5-19% for the 7 other HM1.24 peptides).
      Antigen recognition by the HM1.24 aa22-30-specific CD8(+) T cells was HLA-A2
      restricted (ELISpot with HLA-A2-blocking antibodies: median, 15; range, 14-18
      spots/well; isotype-control antibodies: median, 47; range, 44-48). HM1.24-aa22-30
      specific CD8(+) T cells lysed HLA-A2(+) myeloma-derived cell lines ((51)Cr
      release assay: XG-1 vs MCF-7, 91% vs 0%; U266 vs MCF-7, 38% vs 4.2%; IM-9 vs RPMI
      8226, 22% vs 0%). Using the cross-reactive Neisseria meningitidis peptide
      LLSLGIGILV-specific CD8(+) T cells recognizing target cells loaded with the
      HM1.24 aa22-30 peptide (LLLGIGILV) as well as the myeloma-derived cell line U266
      could be expanded from MM patients. The HM1.24 gene was expressed at comparable
      levels by plasma cells from 65 MM patients, 7 patients with monoclonal gammopathy
      of undetermined significance, and 7 ND. CONCLUSIONS: HM1.24 aa22-30 is a newly
      identified HLA-A2-restricted T-cell epitope that is processed and presented by
      major histocompatibility complex class I. Specifically activated CD8(+) T cells
      are able to lyse MM cell lines. We conclude that HM1.24 aa22-30 represents a
      suitable candidate target for a specific peptide-based immunotherapy of MM.

PMID- 16569596
TI  - In vitro expansion of polyclonal T-cell subsets for adoptive immunotherapy by
      recombinant modified vaccinia Ankara.
AB  - OBJECTIVE: Adoptive cellular therapy of cytomegalovirus (CMV)-specific T cells in
      allogeneic hematopoietic stem cell transplantation (HSCT) patients is a promising
      approach for controlling CMV viremia and its morbidity. We sought to develop a
      clinically suitable strategy to dually expand infusible CD8(+) and CD4(+) T-cell
      subsets specific for CMV. METHODS: Polyclonal CMV T-cell lines were generated
      using peripheral blood mononuclear cell (PBMCs) treated with synthetic single
      stranded CpG motif-containing oligodeoxynucleotides (ODNs) and infected with
      recombinant (r) modified vaccinia Ankara (MVA) expressing CMV antigens. Cultures
      derived from 12 healthy CMV-positive donors were analyzed using chromium release
      and lymphoproliferation assays, intracellular staining for interferon-gamma (IFN
      gamma), and HLA tetramers. RESULTS: A 3-day incubation with a combination of ODN
      2006 and 2216 was found to reproducibly generate a highly rMVA infectable
      population of PBMCs with concomitant high expression of CMV antigens. CpG ODN
      treated autologous PBMCs infected with rMVA elicited a 30-fold average expansion
      of both CMV-specific CD4(+) and CD8(+) T cells in 10 days. The enriched T-cell
      populations showed minimal alloreactivity, high levels of CMV-specific HLA class
      I tetramer binding, cytotoxic activity, and IFN-gamma production from both CD8(+)
      and CD4(+) T cells. CONCLUSIONS: The ability to quickly produce autologous
      professional antigen-presenting cells, capable of stimulating clinically useful
      amounts of CMV-specific CD4(+) and CD8(+) T-cell lines, enhances the
      attractiveness of using rMVA for immunotherapeutic interventions to manage HSCT
      related CMV disease.

PMID- 16569597
TI  - Involvement of insulin-like growth factor-I and insulin-like growth factor
      binding proteins in pro-B-cell development.
AB  - OBJECTIVE: Insulin-like growth factor (IGF)-binding proteins (IGFBPs) are a
      family of proteins thought to modulate IGF function. By employing an in vitro
      culture system of human hematopoietic stem cells cocultured with murine bone
      marrow stromal cells, we examined the effects of IGF-I and IGFBPs on early B-cell
      development. MATERIALS AND METHODS: Human CD34(+) bone marrow cells were
      cocultured with murine stromal MS-5 cells for 4 weeks, and pro-B-cell number was
      analyzed by flow cytometry. After administration of reagents that are supposed to
      modulate IGF-I or IGFBP function to the culture, the effect on pro-B-cell
      development was examined. RESULTS: After cultivation for 4 weeks, effective
      induction of pro-B-cell proliferation was observed. Experiments using several
      distinct factors, all of which neutralize IGF-I function, revealed that
      impairment of IGF-I function results in a significant reduction in pro-B-cell
      development from CD34(+) cells. In addition, when the effect of recombinant
      proteins of IGFBPs and antibodies against IGFBPs were tested, IGFBP-3 was found
      to inhibit pro-B-cell development, while IGFBP-6 was required for pro-B-cell
      development. CONCLUSIONS: IGF-I is essential for development of bone marrow
      CD34(+) cells into pro-B cells. Moreover, IGFBPs are likely involved in
      regulation of pro-B-cell development.

PMID- 16569598
TI  - Identification of tenascin-C as a key molecule determining stromal cell-dependent
      erythropoiesis.
AB  - OBJECTIVE: We previously established 33 bone marrow stromal cell lines from SV40
      T-antigen transgenic mice. Of these, 27 clones supported erythroid colony
      formation, while 6 did not. The objective of this study is to identify the
      molecules that determine these erythroid colony-forming activities. MATERIALS AND
      METHODS: We compared gene expression profiling by DNA microarray between cell
      lines that support erythropoiesis (E(+); TBR9, 184, 31-2) and cell lines that do
      not (E(-); TBR17, 33, 511). Among the differentially expressed genes, we selected
      candidate genes with results of quantitative reverse transcriptase polymerase
      chain reaction, and examined the effect of small interfering RNA (siRNA) and the
      addition of exogenous proteins on the erythroid colony formation. RESULTS: Out of
      7226 genes examined, 138 and 282 genes were upregulated and downregulated in E(+)
      by threefold or more, respectively. We have selected one of the upregulated
      genes, tenascin-C (TN-C), as a candidate. Expressions of TN-C in E(+) were all
      higher than the three E-cell lines, with a mean of 3.6-fold. The number of
      erythroid colonies in the presence of TN-C siRNA was significantly lower than
      that of control siRNA in TBR9 (20.7 +/- 6.3 vs 4.7 +/- 4.8 colonies; p = 0.01)
      and in TBR184 (13.3 +/- 5.3 vs 0.3 +/- 0.5; p = 0.02). Moreover, addition of
      exogenous TN-C enhanced the number of erythroid colonies in TBR184 (13.3 +/- 3.5
      vs 20.0 +/- 2.0; p = 0.04) and in TBR31-2 (7.5 +/- 3.1 vs 13.5 +/- 2.6; p =
      0.03). CONCLUSION: These results suggest that TN-C is responsible for determining
      the stromal cell-dependent erythropoiesis.

PMID- 16569599
TI  - Characterization of 17 new cases of X-linked chronic granulomatous disease with
      seven novel mutations in the CYBB gene.
AB  - OBJECTIVE: Molecular identification and clinical characterization of genetic
      mutations in patients with X-linked chronic granulomatous disease (CGD). PATIENTS
      AND METHODS: Genomic DNA from 17 male patients with proven X-linked CGD based on
      clinical history, clinical examination, and specific granulocyte function tests
      were amplified by polymerase chain reaction (PCR) for sequences of the CYBB gene
      encoding gp91-phox. Mutations in the resulting PCR products were identified by
      DNA sequencing. RESULTS: Sequence analysis revealed four deletions (453_454delAG;
      802delC; 962delG; 993delG), one combined deletion/insertion/duplication
      [156_173delTCAGCACTGGCACTGGCC/174_175insT/175_176insCCTGCCTGAATTTCT(dupl187_200)]
      one insertion (574_575insCCTCAT), four nonsense mutations (332G > A; 402C > T;
      690C > T; 1340C>G), two missense mutations (933A > C; 1041A > C) and four
      potential splice-site mutations (5'intron1 gt-->at; 3'intron1ag-->at; 5'intron3
      gtaag-->gtaaa; 5'intron4 gtaa-->ctaa). Seven of these mutations were indeed
      novel, whereas four mutations not previously reported to the X-CGDbase were found
      to be of the same type as database reports of unrelated families. The six
      remaining mutations have been reported previously to the X-CGDbase but have as
      yet not been described in detail. CONCLUSION: Our findings underline the great
      heterogeneity of mutations involving the CYBB gene. Neither a mutational hot spot
      in the gp91-phox gene nor a clear correlation between molecular defect and
      clinical manifestation in unrelated families could be demonstrated. Remarkable is
      a splice-site mutation (5'intron3 gtaag-->gtaaa) identified in a 40-year-old
      patient with late onset "adult" CGD and residual nicotinamide adenine
      dinucleotide phosphate reduced oxidase activity. The enormous delay of clinical
      symptoms of this particular mutation could be explained by an age-related
      variable sensitivity of the splicing machinery to the present splice-site
      mutation.

PMID- 16569600
TI  - The heterogeneity of human mesenchymal stem cell preparations--evidence from
      simultaneous analysis of proteomes and transcriptomes.
AB  - OBJECTIVE: Mesenchymal stem cells (MSC) raise high hopes in clinical
      applications. However, the lack of common standards and a precise definition of
      MSC preparations remains a major obstacle in research and application of MSC.
      Whereas surface antigen markers have failed to precisely define this population,
      a combination of proteomic data and microarray data provides a new dimension for
      the definition of MSC preparations. METHODS: In our continuing effort to
      characterize MSC, we have analyzed the differential transcriptome and proteome
      expression profiles of MSC preparations isolated from human bone marrow under two
      different expansion media (BM-MSC-M1 and BM-MSC-M2). RESULTS: In proteomics, 136
      protein spots were unambiguously identified by MALDI-TOF-MS and corresponding
      cDNA spots were selected on our "Human Transcriptome cDNA Microarray."
      Combination of datasets revealed a correlation in differential gene expression
      and protein expression of BM-MSC-M1 vs BM-MSC-M2. Genes involved in metabolism
      were more highly expressed in BM-MSC-M1, whereas genes involved in development,
      morphogenesis, extracellular matrix, and differentiation were more highly
      expressed in BM-MSC-M2. Interchanging culture conditions for 8 days revealed that
      differential expression was retained in several genes whereas it was altered in
      others. CONCLUSION: Our results have provided evidence that homogeneous BM-MSC
      preparations can reproducibly be isolated under standardized conditions, whereas
      culture conditions exert a prominent impact on transcriptome, proteome, and
      cellular organization of BM-MSC.

PMID- 16569601
TI  - Improved survival following induction of GVHD following lipopolysaccharide
      immunization.
AB  - OBJECTIVE: Graft-vs-host disease (GVHD) is still the primary limitation to the
      wider application of allogeneic bone marrow transplantation (BMT). On the one
      hand, it predisposes transplant recipients to risk of bacterial, fungal, and
      viral infections, on the other, lipopolysaccharide (LPS), an endotoxin found in
      the cell walls of gram-negative bacteria, has been shown to play a significant
      role in the development and severity of GVHD following allogeneic myeloablative
      BMT. Our study focused on immunization of recipient and donor mice with endotoxin
      prior to transplantation, in an attempt to reduce mortality caused by gram
      negative bacterial infections posttransplantation. MATERIALS AND METHODS: In one
      experiment, recipient mice were immunized with LPS prior to BMT, whereas in
      another experiment, donor mice were immunized prior to BMT. The mice were
      evaluated for development of GVHD and for survival. RESULTS: Our results showed
      that injection of low-dose LPS to mice prior to induction of GVHD with allogeneic
      spleen cells saved more than 40% of the recipients, whereas all mice in the
      untreated control group died. The survival of recipients of spleen cells from
      immunized donors rose to 54% and clinical signs of GVHD were attenuated as
      compared to control mice inoculated with spleen cells obtained from unimmunized
      donors. CONCLUSION: This immunization protocol suggests that immunization of the
      donor or the recipient against LPS prior to transplantation may be protective
      against gram-negative bacteria.

PMID- 16569602
TI  - Commercial applications of microalgae.
AB  - The first use of microalgae by humans dates back 2000 years to the Chinese, who
      used Nostoc to survive during famine. However, microalgal biotechnology only
      really began to develop in the middle of the last century. Nowadays, there are
      numerous commercial applications of microalgae. For example, (i) microalgae can
      be used to enhance the nutritional value of food and animal feed owing to their
      chemical composition, (ii) they play a crucial role in aquaculture and (iii) they
      can be incorporated into cosmetics. Moreover, they are cultivated as a source of
      highly valuable molecules. For example, polyunsaturated fatty acid oils are added
      to infant formulas and nutritional supplements and pigments are important as
      natural dyes. Stable isotope biochemicals help in structural determination and
      metabolic studies. Future research should focus on the improvement of production
      systems and the genetic modification of strains. Microalgal products would in
      that way become even more diversified and economically competitive.

PMID- 16569603
TI  - Improvement on production of (R)-4-chloro-3-hydroxybutyrate and (S)-3-hydroxy
      gamma-butyrolactone with recombinant Escherichia coli cells.
AB  - (R)-4-Chloro-3-hydroxybutyrate (CHB) and (S)-3-hydroxy-gamma-butyrolactone (HL)
      are used for the synthesis of biologically and pharmacologically important
      compounds. Enterobacter sp. DS-S-75 was found to have the unique activity to
      convert (S)-CHB in the racemate to (S)-HL through asymmetric dechlorination,
      hydrolysis, and lactonization. As a result, the remaining (R)-CHB and formed (S)
      HL could be obtained in a one-pot reaction. We purified the CHB degrading enzyme
      which catalyzing these reactions and isolated the coding gene from the strain DS
      S-75 in order to improve the productivity of these compounds using the
      transformant. Interestingly, the purified enzyme showed not only dechlorinating,
      but also hydrolyzing activities on CHB and the similar carboxylic esters, it was
      then designated CHB hydrolase, and appears to be a novel enzyme. The gene had
      1101 bp encoding 367 amino acids including a signal peptide composed of 25
      residues. The deduced amino acid sequence contained a conserved region generally
      found in esterases and lipases, but did not have significant similarity. When
      asymmetric degradation of racemic methyl CHB (CHBM) was performed using a culture
      broth of Escherichia coli DH5alpha transformed with the isolated gene, the
      reaction time was shortened 20-fold over that of the strain DS-S-75, and the
      maximum concentration of the substrate could be increased from 8% to 15% (w/v).
      Moreover, both of the obtained residual (R)-CHBM and the formed (S)-HL had high
      optical purities (>99% e.e.).

PMID- 16569604
TI  - Simultaneous measurement of chlorophyll and astaxanthin in Haematococcus
      pluvialis cells by first-order derivative ultraviolet-visible spectrophotometry.
AB  - A first-order derivative spectrophotometric method has been developed for the
      simultaneous measurement of chlorophyll and astaxanthin concentrations in
      Haematococcus pluvialis cells. Acetone was selected for the extraction of
      pigments because of its good sensitivity and low toxicity compared with other
      organic solvents tested; the tested solvents included acetone, methanol, hexane,
      chloroform, n-propanol, and acetonitrile. A first-order derivative
      spectrophotometric method was used to eliminate the effects of the overlaping of
      the chlorophyll and astaxanthin peaks. The linear ranges in 1D evaluation were
      from 0.50 to 20.0 microg x ml(-1) for chlorophyll and from 1.00 to 12.0 microg x
      ml(-1) for astaxanthin. The limits of detection of the analytical procedure were
      found to be 0.35 microg x ml(-1) for chlorophyll and 0.25 microg x ml(-1) for
      astaxanthin. The relative standard deviations for the determination of 7.0 microg
      x ml(-1) chlorophyll and 5.0 microg x ml(-1) astaxanthin were 1.2% and 1.1%,
      respectively. The procedure was found to be simple, rapid, and reliable. This
      method was successfully applied to the determination of chlorophyll and
      astaxanthin concentrations in H. pluvialis cells. A good agreement was achieved
      between the results obtained by the proposed method and HPLC method.

PMID- 16569605
TI  - Kinetics of endoglucanase and endoxylanase uptake by soybean seeds.
AB  - The uptakes of endoglucanase and endoxylanase by soybean were studied by
      measuring the fluorescent intensity of a carboxyfluorescein. The disappearance
      rates of these enzymes from solution were compared with predictions from
      different models. The Freundlich model provided the best fit for our data. Enzyme
      concentration in the solution did not change significantly after 11 d, and
      therefore it was assumed that equilibrium was reached. Average mass transfer
      coefficient was calculated for both endoglucanase and endoxylanase from the plot
      of the rate of uptake against (C(l av) -Cl*) and a value of 4 x 10(-5) ms(-1) was
      obtained. K value was used to calculate the effective diffusivities of the two
      enzymes assuming a slice. It is found that K was asymptotic with long residence
      times, and a value of 4.8 x 10(-10) m2 s(-1) was obtained.

PMID- 16569606
TI  - Effects of mechanical stimuli and microfiber-based substrate on neurite outgrowth
      and guidance.
AB  - We introduced mechanical stimuli and micropatterned substrate with microfibers to
      investigate their effects on neurite outgrowth along with nerve growth factor in
      vitro. Two types of surface morphology were used: a surface that was coated by
      laminin alone and a surface where in microfibers was added on the laminin
      surface. PC-12 cells were seeded on both surface types and cultured for 2 d. The
      magnitudes of shear stresses ranged from 0.10 to 1.50 Pa. Two days after
      stimulation by shear stress, neurite outgrowth and its direction were measured by
      F-actin staining and digital image processing. When a shear stress of 0.50 Pa was
      applied, neurons were most highly aligned with microfibers. The average length of
      neurite outgrowth with microfibers was largest at a shear stress of 0.25 Pa. The
      results suggest that micropatterned fibers and fluid-induced shear stress are
      promising for stimulating neurite outgrowth in a desired direction.

PMID- 16569607
TI  - Improved L-threonine production of Escherichia coli mutant by optimization of
      culture conditions.
AB  - L-threonine production was investigated in a minimal salt medium using L
      threonine-overproducing Escherichia coli MT201, derived from E. coli K-12. It was
      observed that dry cell weight reached 12.5 g/l with 15.9 g/lL-threonine. To
      increase dry cell weight and L-threonine production, the fermentation process was
      optimized. When biotin was added as growth factor, L-threonine production reached
      52.0 g/l from 15.9 g/l without biotin. Dry cell weight and L-threonine production
      were further increased by continuous feeding of the feed media with an optimized
      L-methionine concentration (5.0 g/l). However, high-cell-density culture caused
      oxygen-limited condition, which resulted in the accumulation of organic acids. To
      overcome this problem, oxygen-enriched air was supplied to the fermentor with the
      minimal salt medium. Under these optimal conditions, we achieved an L-threonine
      production of 80.2 g/l in the minimal salt medium.

PMID- 16569608
TI  - Stabilization of free and immobilized enzymes using hyperthermophilic chaperonin.
AB  - Chaperonins suppress the denaturation of proteins and promote protein folding in
      vivo. Because hyperthermophilic chaperonins are expected to be used as a
      stabilizer for proteins, the effects of a group II chaperonin from a
      hyperthermophilic archaeum, Thermococcus strain KS-1 (T. KS-1 cpn), on the
      stabilization of mesophilic and thermophilic free enzymes and an enzyme co
      immobilized with T. KS-1 cpn were studied. T. KS-1 cpn prevented the thermal
      inactivation of yeast alcohol dehydrogenase (ADH), jack bean urease, and Thermus
      flavus malate dehydrogenase (MDH) at high temperatures. T. KS-1 cpn also improved
      the long-term stability of ADH at lower temperatures. Moreover, the residual ADH
      activity of ADH co-entrapped with T. KS-1 cpn was improved and maintained at a
      higher level than that of the entrapped ADH without chaperonin. T. KS-1 cpn is
      useful for the stabilization of free and immobilized enzymes and applicable to
      various fields of biotechnology.

PMID- 16569609
TI  - Prediction of peptide binding to major histocompatibility complex class II
      molecules through use of boosted fuzzy classifier with SWEEP operator method.
AB  - To treat autoimmune diseases, it is important to identify which peptides bind to
      major histocompatibility complex (MHC) class II molecules (HLA-DRs). Predicting
      the peptides that bind to MHC class II molecules can effectively reduce the
      number of experiments required for identifying helper T cell epitopes. In our
      previous study, we applied fuzzy neural networks (FNNs) to solve this problem.
      However, an FNN requires a long calculation time and a large number of peptides;
      this means performing several experiments. In this study, we applied a boosted
      fuzzy classifier with the SWEEP operator method (BFCS) to solve this problem. For
      comparison, two other conventional modeling methods, namely, support vector
      machine and FNN combined with the SWEEP operator method (FNN-SWEEP) instead of
      using solely an FNN, were employed. Compared with FNN, FNN-SWEEP is extremely
      fast and has an almost identical prediction accuracy. The model constructed by
      BFCS showed an accuracy approximately 5%-10% higher than that constructed by FNN
      SWEEP. In addition, BFCS was 30,000-120,000 times faster than FNN-SWEEP. This
      result suggests that BFCS has the potential to function as a new method of
      predicting peptides that bind to various protein receptors.

PMID- 16569610
TI  - Subsurface biobarrier formation by microorganism injection for contaminant plume
      control.
AB  - The concept of an in situ mixture of residual soil and aerobic microorganisms as
      a biobarrier for controlling contaminant plume was evaluated in this study.
      Azotobacter chroococcum was inoculated into soil with oxygen as the electron
      acceptor and appropriate substrate to induce biofilm clog soil pores. The
      hydraulic conductivity of soil decreased by 1/8000 while substrate and oxygen
      were provided to the injected microorganism, and increased by 400% when no
      substrate was provided. A series of column experiments were carried out to
      measure the hydraulic conductivity of soil specimens. The results showed that the
      highest hydraulic conductivity reduction occurred when the substrate and electron
      acceptors were first introduced, and this reduction increased toward the outlet
      of the column. The substrate was consumed mostly at the inlet and was distributed
      with time. The analysis of volatile substances after the test showed that the
      inlet had a high organic content and the outlet had a low organic content.

PMID- 16569611
TI  - Effects of long-term ingestion of difructose anhydride III (DFA III) on
      intestinal bacteria and bile acid metabolism in humans.
AB  - Changes in the intestinal microbiota of 10 human subjects with long-term
      ingestion of 3 g/d difructose anhydride III (DFA III; 4 persons, 2 months; 3
      persons, 6 months; and 3 persons, 12 months) were examined by denaturing gradient
      gel electrophoresis (DGGE). According to the answers to questionnaires, the
      subjects were divided into two groups (constipated and normal). The DGGE profile
      was different for every individual and each subject had unique profiles of
      intestinal microbiota. In the DGGE profiles of constipated subjects, the
      intensities of bands related to Bacteroides spp. increased. Moreover, the DFA III
      assimilating bacteria, Ruminococcus sp. were isolated from subjects who ingested
      DFA III for 12 months. These strains showed 95% similarity of their 16S rDNA
      sequences with that of Ruminococcus obeum ATCC 29174(T) (X85101) and produced
      large amounts of acetic acid. DFA III ingestion for 2 months tended to increase
      total organic acids in feces, and tended to decrease fecal pH and the secondary
      bile acid (SBA) ratio in total bile acids. The SBA ratio in total bile acids
      corresponded to fecal pH. The production of SBA was decreased by low pH in vitro.
      These results indicated that DFA III ingestion in humans tended to lower
      intestinal pH, inhibited bile acid 7alpha-dehydroxylation activities and also
      tended to decrease the SBA ratios in total bile acids. Moreover, as another cause
      for the decrease in the SBA ratio in total bile acids, it was suggested that the
      number of bile acid 7alpha-dehydroxylating bacteria were decreased by DFA III
      ingestion.

PMID- 16569612
TI  - Purification and characterization of prodigiosin produced by integrated
      bioreactor from Serratia sp. KH-95.
AB  - To date, prodigiosin and its analogues which have been shown to have anticancer,
      cytotoxic and immunosuppressive activities have been isolated from Serratia,
      Pseudomonas and Streptomyces species, and chemically synthesized. In a previous
      study, the red pigment content in Serratia sp. KH-95 was enhanced using a casein
      enriched medium. Recently, an integrated bioreactor with an internal adsorbent
      has been developed to increase the production yield and allow easy recovery of
      the pigment. Thus, this study focused on both purifying and identifying a single
      red pigment from several pigments attached to the adsorbent in an integrated
      bioreactor. The red pigment was extracted directly from the internal adsorbent
      using acidified methanol and phase separation. Subsequently, it was purified by
      silica gel chromatography and high performance liquid chromatograph (HPLC). As a
      result, pure prodigiosin was identified by structural studies as a pigment. Also,
      this downstream procedure that uses the integrated bioreactor can be applied to
      the direct production and purification of other prodigiosin analogues and
      hydrophobic alkaloid compounds from several microorganisms.

PMID- 16569613
TI  - Oxalate enhances protein synthesis in cell-free synthesis system utilizing 3
      phosphoglycerate as energy source.
AB  - Herein, we report our results showing that the productivity of cell-free protein
      synthesis can be enhanced through the regulation of the in vitro metabolism of an
      energy source. In a reaction mixture utilizing 3-phosphoglycerate (3PG) as an
      energy source, the supply of ATP was significantly enhanced when the reaction
      mixture was supplied with sodium oxalate, a potent inhibitor of
      phosphoenolpyruvate synthetase (PPS). The productivity of protein synthesis was
      also increased by approximately 70% upon the addition of oxalate. It was presumed
      that this enhancement in ATP supply resulted from the prevention of the pyruvate 
      -> PEP reaction, which causes nonproductive ATP consumption. For the initial
      presence of 2.1 mM sodium oxalate, approximately 720 microg/ml chloramphenicol
      acetyltransferase (CAT) was produced after 3 h of incubation at 37 degrees C.

PMID- 16569614
TI  - Purification and characterization of extracellular cysteine protease inhibitor,
      ECPI-2, from Chlorella sp.
AB  - An extracellular cysteine protease inhibitor (ECPI-2) was purified to homogeneity
      from the culture filtrate of Chlorella sp. 4533 by the combination of various
      column chromatographies. The molecular mass of the inhibitor was estimated to be
      340 kDa by SDS-PAGE. The inhibitor was extremely heat-stable under acidic or
      neutral condition. ECPI-2 exhibited an inhibitory activity against the
      proteolytic activity of papain, ficin, or chymopapain, but not against stem
      bromelain or cathepsin B. The inhibitor showed no inhibitory activity against
      trypsin, alpha-chymotrypsin or thermolysin. ECPI-2 contains 33.6% carbohydrate
      residues by weight and inhibits papain at a molar ratio of 1:2. The proteolysis
      of the inhibitor by trypsin or alpha-chymotrypsin was apparent, but the
      inhibitory activity of ECPI-2 was unaffected by these enzymes. The alpha
      chymotrypsin hydrolysis product from ECPI-2 was further separated into six
      fractions by gel filtration. From these results, it is suggested that ECPI-2 has
      several reactive sites for papain.

PMID- 16569615
TI  - D-lactic acid production by metabolically engineered Saccharomyces cerevisiae.
AB  - Poly D-lactic acid is an important polymer because it improves the
      thermostability of poly L-lactic acid by the stereo complex formation. We
      constructed a metabolically engineered Saccharomyces cerevisiae that produces D
      lactic acid efficiently. In this recombinant, the coding region of pyruvate
      decarboxylase 1 (PDC1) was completely deleted, and two copies of the D-lactate
      dehydrogenase (D-LDH) gene from Leuconostoc mesenteroides subsp. mesenteroides
      strain NBRC3426 were introduced into the genome. The D-lactate production reached
      61.5 g/l, the amount of glucose being transformed into D-lactic acid being 61.2%
      under neutralizing conditions. Additionally, the yield of free D-lactic acid was
      also shown to be 53.0% under non-neutralizing conditions. It was confirmed that D
      lactic acid of extremely high optical purity of 99.9% or higher. Our finding
      obtained the possibility of a new approach for pure d-lactic acid production
      without a neutralizing process compared with other techniques involving lactic
      acid bacteria and transgenic Escherichia coli.

PMID- 16569616
TI  - Supplementation effects of hydroxyectoine on proline uptake of downshocked
      Brevibacterium sp. JCM 6894.
AB  - Downshock treatment of the halotolerant Brevibacterium sp. JCM 6894 was a
      prerequisite for proline uptake which is a function for cell survival.
      Hydroxyectoine served as an effective stimulator for the proline uptake and cell
      survival of the downshocked cells of this strain. Duration of osmotic downshock,
      downshock strength, and the kinds of osmolyte affected the efficient rate of
      growth (ERG) and the uptake of proline. A shorter duration of osmotic downshock,
      that is <or=1 h, induced higher ERG values and stimulated proline uptake,
      compared with those of non-downshocked cells when incubated with hydroxyectoine
      and proline. These activities, however, were gradually suppressed with the
      prolongation of the duration of osmotic downshock. When the cells grown in KCl
      containing medium were subjected to downshock treatment for 1 h, their activities
      were enhanced more remarkably than those of cells grown in NaCl-containing
      medium.

PMID- 16569617
TI  - Association of photosynthesis and photocatalytic inhibition of algal growth by
      TiO2.
AB  - The relationship of photosynthesis and photocatalytic inhibition of algal growth
      (Chroococcus sp.) by TiO2 was investigated by an ATP assay under ultraviolet (UV)
      and fluorescent light (FL) irradiations. The adverse effects of what on
      Chroococcus sp. growth in the TiO2+FL+UV run are larger than those in the TiO2+UV
      run. The difference is considered to be caused by oxygen generated by Chroococcus
      sp. under FL irradiation. A rate equation for the relationship of light
      irradiation intensity to rate of decrease in the Chroococcus sp. population on
      the basis of the Langmuir-Hinshelwood model has been proposed. The experimental
      data are in good agreement with the proposed model. In this study, the optimum FL
      intensity is 0.51 mW/cm2.

PMID- 16569618
TI  - Expression and purification of recombinant human annexin A2 in Pichia pastoris
      and utility of expression product for detecting annexin A2 antibody.
AB  - Annexin A2, a Ca2+-dependent phospholipid binding protein, is abundantly
      expressed in various human organs, which exists as either a membrane-associated,
      cytosolic or soluble form in serum. We constructed expression systems for
      recombinant human annexin A2 (rhA2) using Pichia pastoris. The systems are
      designed to secrete rhA2 as either the N- or C-terminally His6-tagged form to
      facilitate purification. Both types of rhA2 were overexpressed, but in the N
      terminal-truncated form as revealed from the results of N-terminal amino acid
      sequencing and Western blotting. Therefore, further purification of N-terminally
      His6-tagged rhA2 was not feasible because of the removal of the N-terminal His6
      tag sequence. C-terminally His6-tagged rhA2 was expressed as either a
      glycosylated or a nonglycosylated form, and the nonglycosylated form was purified
      using the combination of nickel-immobilized affinity, concanavalin A and cation
      exchanged column chromatographies. The solid-phase binding of rhA2 was examined
      by enzyme-linked immunosorbent assay (ELISA), which revealed the specific
      reactivity of rhA2 against an anti-annexin A2 monoclonal antibody. These results
      suggest that the expression system using P. pastoris is useful for the
      preparation of rhA2 that is applicable to the ELISA detection of the anti-annexin
      A2 antibody.

PMID- 16569619
TI  - Coliphage derived sialidase preferentially recognizes nonreducing end of
      polysialic acid.
AB  - Bacteriophages infecting Escherichia coli K1 strains generally have endotype
      polysialic acid-degrading enzymes. We studied the digestion mechanism of a
      sialidase associated with the coliphage 63D using polysialic acid radiolabeled at
      its nonreducing end or reducing end. It was found that this enzyme preferentially
      recognizes the nonreducing end of polysialic acid, suggesting that the 63D
      associated sialidase does not randomly digest its substrate but acts like an
      exotype glycosidase.

PMID- 16569620
TI  - The relationship between allergy and homeopathy: a framework.

PMID- 16569621
TI  - Homeopathy and respiratory allergies: a series of 147 cases.
AB  - Allergies, especially respiratory allergies, are one of the indications for which
      homeopathic treatment is most frequently sought. The progress of 147 cases of
      respiratory allergy since in private homeopathic practice is reported here. Only
      two cases of ear, nose and throat (ENT) allergies out of a total of 105 showed no
      improvement, no patients deteriorated. Two cases with worsening and three without
      improvement were noted out of 42 cases of pulmonary allergies. The constitutional
      homeopathic remedies varied, Lycopodium, Pulsatilla and Sulphur were most
      frequently prescribed for ENT allergies, there was no predominantly prescribed
      remedy in the pulmonary allergy group. Thirty one cases of respiratory allergies
      consulted only once. The reasons for such a state have been reviewed. If all
      these cases were therapeutic failures, the success rate of the homeopathic
      treatment is 87.6%.

PMID- 16569622
TI  - An exploratory retrospective study of people suffering from hypersensitivity
      illnesses who attend medical or classical homeopathic treatment.
AB  - The objective of this study is to describe patients who had treatment for
      hypersensitivity illnesses by general practitioners (GPs) or classical homeopaths
      (CHs) and the patients' self-reported effectiveness of the treatment received.
      The data stems from an exploratory retrospective study amongst 88 Danish patients
      (response rate 58%) suffering from hypersensitivity illnesses, who chose
      treatment from one of six GPs or one of 10 CHs who participated in the project.
      The patients themselves selected their treatment. The GPs or the CHs considered
      that the patient's treatment was complete or that the patient was in a situation
      of current 'maintenance treatment'. The patients' primary reason for consulting
      the GP or the CH was that they were suffering from hypersensitivity illnesses. No
      significant difference was found between the two groups of patients in relation
      to age, education and duration of hypersensitivity symptoms. The CH patients were
      more likely to be employed in teaching, research, health care or the social
      sector compared to GP patients. The two groups of patients were similar in
      respect of their health at the start of the treatment, 57% of the patients who
      consulted a CH experienced an improvement of their state of health compared to
      24% of the GP patients. Both groups of patients experienced an improvement of
      their psychological health after treatment. Logistic regression analysis showed
      that the GP or CH was the only significant effect variable. The results are based
      on the patients' retrospective, self-reported effectiveness of the treatments.

PMID- 16569623
TI  - Opinions and self-reported health status of Italians seeking homeopathic
      treatment.
AB  - The use of homeopathy is increasing worldwide. This multi-centre cross-sectional
      study aims to describe the opinions and self-reported health status of a sample
      of Italian people seeking homeopathic care. A self-administered questionnaire
      including socio-demographic characteristics, knowledge and opinions about
      homeopathy, personal experience with homeopathy, and, self-reported health status
      (SF-12), was administered to a sample of people who had sought homeopathy. Of a
      possible 1229 individuals invited to participate, 1223 did so. The majority of
      the participants were female, young (mean age 42 years), well educated (mean 13
      years of education). The reason for seeking care was for either physical or
      emotional conditions. Most participants had fair to good knowledge of homeopathy,
      and the self-experienced effect (subjective judgment on efficacy) was good
      regardless of the type of health condition reported. The Physical Component
      Summary (PCS-12) scores were similar to the general Italian population, but the
      Mental Component Summary (MCS-12) scores were lower in all relevant strata
      examined. This study provides information on the characteristics of people
      seeking homeopathic care, in particular the results of the SF-12 self-reported
      health status evaluation.

PMID- 16569624
TI  - A Bayesian perspective on the reliability of homeopathic repertories.
AB  - An interim assessment of likelihood ratio of homeopathic symptoms shows that
      there are serious flaws in Kent's repertory. The system of expressing
      relationship between symptoms and expected results from medicines by type-face is
      unclear and unreliable. Bayesian methods can improve this and expand the
      possibilities of the repertory including the possibility of interpreting the
      absence of expected symptoms.

PMID- 16569625
TI  - Evaluation of isopathic treatment of Salmonella enteritidis in poultry.
AB  - BACKGROUND: Salmonellosis is a common problem worldwide in commercially reared
      poultry. It is associated with human Salmonellosis. No fully satisfactory method
      of control is available. METHOD: Nosodes to an antibiotic-resistant strain of
      Salmonella enterica serovar Enteritidis in D30 (30X) potency were prepared. One
      day old chicks (N = 180) were divided into four groups: two control and two
      different preparations of the nosode. Treatments were administered in drinking
      water for 10 days. The birds were challenged by a broth culture of the same
      Salmonella, by mouth, on day 17. Cloacal swabs were taken twice weekly for
      Salmonella enterica serovar Enteritidis. RESULTS: Birds receiving active
      treatment were less likely to grow the strain of Salmonella from cloacal swabs
      compared to control. CONCLUSION: Isopathy is low cost and non-toxic. It may have
      a role to play in the widespread problem of Salmonella in poultry. Further
      research should be conducted.

PMID- 16569626
TI  - Effects of Cina on root-knot disease of mulberry.
AB  - Root-knot disease of mulberry is caused by the nematode Meloidogyne incognita. It
      has important economic implications for sericulture. The homeopathic medicines,
      Cina mother tincture (MT) and potentised Cina 200C, prepared from the flowering
      meristems of Artemisia nilagirica (Clarke) Pamp, were applied by foliar spray on
      mulberry (Morus alba L.) infected with M. incognita juveniles (J2). Pretreatment
      (ending 6 days before inoculation) and post-treatment (starting 6 days after
      inoculation) schedules were tested. The two uninoculated control batches were
      treated with the same procedure with Cina MT and Cina 200C. Both pre- and post
      treatment significantly reduced nematode infection in terms of root gall number
      and nematode population in root. All the treated plants showed improved growth in
      terms of fresh biomass of shoot and root, length of shoot and root, number of
      leaves, leaf surface area, root and leaf-protein content. Cina 200C is more
      effective than Cina MT in all respects of nematode control as well as growth of
      the test plants. Pretreatments show slightly better effects than the post
      treatments. It is interesting that inoculated and treated plants not only are
      less affected by nematodes but also have a better growth than uninoculated,
      untreated control.

PMID- 16569628
TI  - Homeopathy: the Nigerian experience.

PMID- 16569627
TI  - Reiter's disease treated with Nux vomica.
AB  - We report the case of a 35 year-old man suffering from Reiter's disease. He did
      not respond to Lycopodium or Nux vomica in medium dilutions, but did respond to
      Nux vomica in very high potency.

PMID- 16569629
TI  - 20 years ago: The British Homoeopathic Journal, April 1986.

PMID- 16569630
TI  - Effects of childhood infections and vaccination on development of atopy.

PMID- 16569631
TI  - Reply to Varley.

PMID- 16569632
TI  - Formation of F-ring isoprostane-like compounds (F3-isoprostanes) in vivo from
      eicosapentaenoic acid.
AB  - Eicosapentaenoic acid (EPA, C20:5, omega-3) is the most abundant polyunsaturated
      fatty acid (PUFA) in fish oil. Recent studies suggest that the beneficial effects
      of fish oil are due, in part, to the generation of various free radical-generated
      non-enzymatic bioactive oxidation products from omega-3 PUFAs, although the
      specific molecular species responsible for these effects have not been
      identified. Our research group has previously reported that pro-inflammatory
      prostaglandin F2-like compounds, termed F2-isoprostanes (IsoPs), are produced in
      vivo by the free radical-catalyzed peroxidation of arachidonic acid and represent
      one of the major products resulting from the oxidation of this PUFA. Based on
      these observations, we questioned whether F2-IsoP-like compounds (F3-IsoPs) are
      formed from the oxidation of EPA in vivo. Oxidation of EPA in vitro yielded a
      series of compounds that were structurally established to be F3-IsoPs using a
      number of chemical and mass spectrometric approaches. The amounts formed were
      extremely large (up to 8.7 + 1.0 microg/mg EPA) and greater than levels of F2
      IsoPs generated from arachidonic acid. We then examined the formation of F3-IsoPs
      in vivo in mice. Levels of F3-IsoPs in tissues such as heart are virtually
      undetectable at baseline, but supplementation of animals with EPA markedly
      increases quantities up to 27.4 + 5.6 ng/g of heart. Interestingly, EPA
      supplementation also markedly reduced levels of pro-inflammatory arachidonate
      derived F2-IsoPs by up to 64% (p < 0.05). Our studies provide the first evidence
      that identify F3-IsoPs as novel oxidation products of EPA that are generated in
      vivo. Further understanding of the biological consequences of F3-IsoP formation
      may provide valuable insights into the cardioprotective mechanism of EPA.

PMID- 16569633
TI  - The 19 S proteasomal subunit POH1 contributes to the regulation of c-Jun
      ubiquitination, stability, and subcellular localization.
AB  - The AP1 (activator protein 1) transcription factor, c-Jun, is an important
      regulator of cell proliferation, differentiation, survival, and death. Its
      activity is regulated both at the level of transcription and post-translationally
      through phosphorylation, sumoylation, and targeted degradation. The degradation
      of c-Jun by the ubiquitin proteasome pathway has been well established. Here, we
      report that POH1, a subunit of the 19 S proteasome lid with a recently described
      deubiquitinase activity, is a regulator of c-Jun. Ectopic expression of POH1 in
      HEK293 cells decreased the level of c-Jun ubiquitination, leading to significant
      accumulation of the protein and a corresponding increase in AP1-mediated gene
      expression. The stabilization also correlated with a redistribution of c-Jun in
      the nucleus. These effects were reduced by mutation of a cysteine residue in the
      Mpr1 pad1 N-terminal plus motif of POH1 (Cys-120) and appeared to be selective
      for c-Jun, because POH1 had no effect on other proteasomal substrates. Our
      results identify a novel mechanism of c-Jun regulation in mammalian cells.

PMID- 16569634
TI  - Profiling of eicosanoid production in the rat hippocampus during kainic acid
      induced seizure: dual phase regulation and differential involvement of COX-1 and
      COX-2.
AB  - Kainic acid (KA)-induced seizure in rat involves eicosanoid production in the
      brain, but their production mechanism and biological functions are poorly
      understood. We profiled the eicosanoid production during KA-induced seizure by a
      comprehensive lipidomics analysis using liquid chromatography-tandem mass
      spectrometry. Systemic KA administration caused production of large amounts of
      prostaglandin (PG) F(2alpha) and PGD(2) in the hippocampus, with smaller amounts
      of other PGs and hydroxyeicosatetraenoic acids. The production was biphasic,
      which consisted of an initial burst in the first 30 min and a sustained late
      phase production. The initial phase was specific to the hippocampus and was
      blocked by intracerebroventricular administration of KA receptor antagonists. A
      selective cyclooxygenase (COX)-2 inhibitor, NS398, completely inhibited the
      initial phase productions, except for PGD(2) and thromboxane B(2), whose
      productions were also dependent on COX-1. These results suggest that KA signals
      directly stimulate the arachidonic acid cascade in the initial phase and that COX
      1 and COX-2, both constitutively expressed at low levels, differentially
      contribute to PG productions. In the late phase, a sustained PG production in
      hippocampus appears due to the increased COX-2 levels even with a limited
      arachidonic acid supply. The present study demonstrates a dual phase regulatory
      mechanism of eicosanoid production during KA-induced seizure, providing a
      biochemical basis for understanding the biosynthesis and roles of eicosanoids in
      the brain.

PMID- 16569636
TI  - Vma9p (subunit e) is an integral membrane V0 subunit of the yeast V-ATPase.
AB  - The Saccharomyces cerevisiae vacuolar proton-translocating ATPase (V-ATPase) is
      composed of 14 subunits distributed between a peripheral V1 subcomplex and an
      integral membrane V0 subcomplex. Genome-wide screens have led to the
      identification of the newest yeast V-ATPase subunit, Vma9p. Vma9p (subunit e) is
      a small hydrophobic protein that is conserved from fungi to animals. We
      demonstrate that disruption of yeast VMA9 results in the failure of V1 and V0 V
      ATPase subunits to assemble onto the vacuole and in decreased levels of the
      subunit a isoforms Vph1p and Stv1p. We also show that Vma9p is an integral
      membrane protein, synthesized and inserted into the endoplasmic reticulum (ER),
      which then localizes to the limiting membrane of the vacuole. All V0 subunits and
      V-ATPase assembly factors are required for Vma9p to efficiently exit the ER. In
      the ER, Vma9p and the V0 subunits interact with the V-ATPase assembly factor
      Vma21p. Interestingly, the association of Vma9p with the V0-Vma21p assembly
      complex is disrupted with the loss of any single V0 subunit. Similarly, Vma9p is
      required for V0 subunits Vph1p and Vma6p to associate with the V0-Vma21p complex.
      In contrast, the proteolipids associate with Vma21p even in the absence of Vma9p.
      These results demonstrate that Vma9p is an integral membrane subunit of the yeast
      V-ATPase V0 subcomplex and suggest a model for the arrangement of polypeptides
      within the V0 subcomplex.

PMID- 16569635
TI  - Probing the conformation of the prion protein within a single amyloid fibril
      using a novel immunoconformational assay.
AB  - The coexistence of multiple strains or subtypes of the disease-related isoform of
      prion protein (PrP) in natural isolates, together with the observed
      conformational heterogeneity of PrP amyloid fibrils generated in vitro, indicates
      the importance of probing the conformation of single particles within
      heterogeneous samples. Using an array of PrP-specific antibodies, we report the
      development of a novel immunoconformational assay. Uniquely, application of this
      new technology allows the conformation of multimeric PrP within a single fibril
      or particle to be probed without pretreatment of the sample with proteinase K.
      Using amyloid fibrils prepared from full-length recombinant PrP, we demonstrated
      the utility of this assay to define (i) PrP regions that are surface-exposed or
      buried, (ii) the susceptibility of defined PrP regions to GdnHCl-induced
      denaturation, and (iii) the conformational heterogeneity of PrP fibrils as
      measured for either the entire fibrillar population or for individual fibrils.
      Specifically, PrP regions 159-174 and 224-230 were shown to be buried and were
      the most resistant to denaturation. The 132-156 segment of PrP was found to be
      cryptic under native conditions and solvent-exposed under partially denaturing
      conditions, whereas the region 95-105 was solvent-accessible regardless of the
      solvent conditions. Remarkably, a subfraction of fibrils showed immunoreactivity
      to PrPSc-specific antibodies designated as IgGs 89-112 and 136-158. The
      immunoreactivity of the conformational epitopes was reduced upon exposure to
      partially denaturing conditions. Unexpectedly, PrPSc -specific antibodies
      revealed conformational polymorphisms even within individual fibrils. Our studies
      provide valuable new insight into fibrillar substructure and offer a new tool for
      probing the conformation of single PrP fibrils.

PMID- 16569637
TI  - Targeting of calcineurin to an NFAT-like docking site is required for the calcium
      dependent activation of the background K+ channel, TRESK.
AB  - The two-pore domain K(+) channel, TRESK (TWIK-related spinal cord K(+) channel)
      is activated in response to the calcium signal by the calcium/calmodulin
      dependent protein phosphatase, calcineurin. In the present study we report that
      calcineurin also interacts with TRESK via an NFAT-like docking site, in addition
      to its enzymatic action. In its intracellular loop, mouse TRESK possesses the
      amino acid sequence, PQIVID, which is similar to the calcineurin binding
      consensus motif, PXIXIT (where X denotes any amino acids), necessary for NFAT
      (nuclear factor of activated T cells) activation and nuclear translocation.
      Mutations of the PQIVID sequence of TRESK to PQIVIA, PQIVAD, or PQAVAD
      increasingly deteriorated the calcium-dependent activation in the listed order
      and correspondingly reduced the benzocaine sensitivity (a property discriminating
      activated channels from resting ones), when it was measured after the calcium
      signal in Xenopus oocytes. Microinjection of VIVIT peptide, designed to inhibit
      the NFAT-calcineurin interaction specifically, also eliminated TRESK activation.
      The intracellular loop of TRESK, expressed as a GST fusion protein, bound
      constitutively active calcineurin in vitro. PQAVAD mutation as well as addition
      of VIVIT peptide to the reaction abrogated this calcineurin binding. Wild type
      calcineurin was recruited to GST-TRESK-loop in the presence of calcium and
      calmodulin. These results indicate that the PQIVID sequence is a docking site for
      calcineurin, and its occupancy is required for the calcium-dependent regulation
      of TRESK. Immunosuppressive compounds, developed to target the NFAT binding site
      of calcineurin, are also expected to interfere with TRESK regulation, in addition
      to their desired effect on NFAT.

PMID- 16569638
TI  - Redox-dependent matrix metalloproteinase-1 expression is regulated by JNK through
      Ets and AP-1 promoter motifs.
AB  - Reactive oxygen species have been shown to play an important role in the
      regulation of distinct signaling cascades, many of which act upon the production
      of matrix metalloproteinases (MMP). Using a series of redox-engineered cell lines
      we have previously demonstrated that MMP-1 expression is sensitive to the
      alterations in the steady state production of H2O2 (Ranganathan, A. C., Nelson,
      K. K., Rodriguez, A. M., Kim, K. H., Tower, G. B., Rutter, J. L., Brinckerhoff,
      C. E., Epstein, C. J., Huang, T. T., Jeffrey, J. J., and Melendez, J. A. (2001)
      J. Biol. Chem. 276, 14264-14270). In the present study, we investigate the
      molecular mechanisms involved in the H2O2-mediated induction of MMP-1. Mutational
      analysis of an MMP-1 promoter indicates that both the single nucleotide
      polymorphism creating an Ets binding site at -1607 and a proximal AP-1 site at 
      1602 are required for maximal H2O2-dependent transcription. The redox-sensitive
      MMP-1 protein expression requires activation of both ERK1/2 and JNK pathways.
      Importantly, JNK signaling is largely responsible for the H2O2 sensitivity of the
      MMP-1 promoter, whereas ERK1/2 contributes to both its basal and H2O2 dependence.
      H2O2 control of Ets-1 expression was ERK1/2-dependent whereas that of c-Jun
      requires both ERK1/2 and JNK signaling. Chromatin immunoprecipitation assays
      indicate that binding of the histone acetyltransferase, p300, and the
      transcription factors Ets-1 and c-Jun to the MMP-1 promoter is redox sensitive.
      The redox sensitivity of MMP-1 expression is also associated with an increase in
      the abundance of oxidatively inactivated protein-tyrosine phosphatases. Targeted
      cytosolic or mitochondrial scavenging of H2O2 prevented all of the aforementioned
      signals. These studies provide substantial insight into the mechanisms underlying
      the redox-dependent control of MMP-1 and may lead to the development of novel
      targeted antioxidant-based inhibitory therapies for controlling MMP-1 expression
      during degenerative disease processes.

PMID- 16569639
TI  - Physiological and functional interactions between Tcf4 and Daxx in colon cancer
      cells.
AB  - Daxx, a human cell death-associated protein, was isolated as a Tcf4-interacting
      protein, using a yeast two-hybrid screen. Co-immunoprecipitation in HEK-293T
      cells and yeast two-hybrid screen in Y190 cells were performed to identify the
      interaction between Tcf4 with Daxx and to map the binding regions of Tcf4. In the
      nucleus, Daxx reduced DNA binding activity of Tcf4 and repressed Tcf4
      transcriptional activity. Overexpression of Daxx altered the expression of genes
      downstream of Tcf4, including cyclin D1 and Hath-1, and induced G1 phase arrest
      in colon cancer cells. A reduction in Daxx protein expression was also observed
      in colon adenocarcinoma tissue when compared with normal colon tissue. This
      evidence suggests a possible physiological function of Daxx, via interaction with
      Tcf4, to regulate proliferation and differentiation of colon cells.

PMID- 16569640
TI  - Optineurin increases cell survival and translocates to the nucleus in a Rab8
      dependent manner upon an apoptotic stimulus.
AB  - In glaucoma the retinal ganglion cells of the retina die through the induction of
      apoptosis leading to excavation of the optic nerve and blindness. Mutations in
      the optineurin (optic neuropathy inducing) protein were found associated with an
      adult form of glaucoma. To date, the role of optineurin in the neurodegeneration
      process that occurs during glaucoma is still unknown. We now report that in
      response to an apoptotic stimulus, optineurin changes subcellular localization
      and translocates from the Golgi to the nucleus. This translocation is dependent
      on the GTPase activity of Rab8, an interactor of optineurin. Furthermore, we
      demonstrate that the overexpression of optineurin protects cells from H2O2
      induced cell death and blocks cytochrome c release from the mitochondria. A
      mutated form of optineurin, E50K, identified in normal tension glaucoma patients
      loses its ability to translocate to the nucleus and when overexpressed
      compromises the mitochondrial membrane integrity resulting in cells that are less
      fit to survive under stress conditions. The correlation between optineurin
      function and cell survival will be key to begin to understand retinal ganglion
      cell biology and signaling and to design general "survival" strategies to treat a
      disease of such a complex etiology as glaucoma.

PMID- 16569641
TI  - Modulation of voltage-dependent Shaker family potassium channels by an aldo-keto
      reductase.
AB  - The beta subunit (Kvbeta) of the Shaker family voltage-dependent potassium
      channels (Kv1) is a cytosolic protein that forms a permanent complex with the
      channel. Sequence and structural conservation indicates that Kvbeta resembles an
      aldo-keto reductase (AKR), an enzyme that catalyzes a redox reaction using an
      NADPH cofactor. A putative AKR in complex with a Kv channel has led to the
      hypothesis that intracellular redox potential may dynamically influence the
      excitability of a cell through Kvbeta. Since the AKR function of Kvbeta has never
      been demonstrated, a direct functional coupling between the two has not been
      established. We report here the identification of Kvbeta substrates and the
      demonstration that Kvbeta is a functional AKR. We have also found that channel
      function is modulated when the Kvbeta-bound NADPH is oxidized. Further studies of
      the enzymatic properties of Kvbeta seem to favor the role of Kvbeta as a redox
      sensor. These results suggest that Kvbeta may couple the excitability of the cell
      to its metabolic state and present a new avenue of research that may lead to
      understanding of the physiological functions of Kvbeta.

PMID- 16569642
TI  - An interaction between insulin-like growth factor-binding protein 2 (IGFBP2) and
      integrin alpha5 is essential for IGFBP2-induced cell mobility.
AB  - In the study we report here, we tested the hypothesis that insulin-like growth
      factor-binding protein 2 (IGFBP2) promotes cell mobility through its interaction
      with integrin alpha5. Our previous microarray studies showed that IGFBP2
      activates the expression of integrin alpha5. In addition, IGFBP2 has an Arg-Gly
      Asp (RGD) domain, which is a known integrin binding motif. We first confirmed our
      microarray results by showing that the expression of integrin alpha5 is indeed up
      regulated at the protein level in IGFBP2-overexpressing SNB19 glioma cells. Using
      co-immunoprecipitation, we confirmed that IGFBP2 does interact with integrin
      alpha5. To confirm that IGFBP2 interacts directly with integrin alpha5 through
      the RGD domain, we created an RGD --> RGE mutant (D306E) IGFBP2 and stably
      overexpressed the mutant IGFBP2 in the same cell line. Co-immunoprecipitation
      then showed that D306E-IGFBP2 had no detectable binding with integrin alpha5. We
      further observed that IGFBP2-overexpressing cells have extensive cell surface
      lamellipodia, whereas D306E-IGFBP2-overexpressing cells show abundant cell
      surface focal adhesions. Consistent with this, phenotype analysis then showed
      that IGFBP2-overexpressing cells have elevated migration rates compared with
      vector control; in contrast, the migration rates of the D306E-IGFBP2
      overexpressing cells were not elevated and were comparable with that of vector
      control. Decreased expression of integrin alpha5 by small interference RNA in
      IGFBP2-overexpressing cells also reduced cell mobility. Therefore, we have
      concluded that one mechanism by which IGFBP2 activates IGFBP2-induced cell
      mobility is through its interaction with integrin alpha5 and this interaction is
      specifically mediated through the RGD domain on IGFBP2.

PMID- 16569643
TI  - C-terminal fragment of presenilin is the molecular target of a dipeptidic gamma
      secretase-specific inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S
      phenylglycine t-butyl ester).
AB  - Gamma-secretase is a multimeric membrane protein complex composed of presenilin
      (PS), nicastrin, Aph-1 and, Pen-2 that is responsible for the intramembrane
      proteolysis of various type I transmembrane proteins, including amyloid beta
      precursor protein and Notch. The direct labeling of PS polypeptides by transition
      state analogue gamma-secretase inhibitors suggested that PS represents the
      catalytic center of gamma-secretase. Here we show that one of the major gamma
      secretase inhibitors of dipeptidic type, N-[N-(3,5-difluorophenacetyl)-l-alanyl]
      S-phenylglycine t-butyl ester (DAPT), targets the C-terminal fragment of PS,
      especially the transmembrane domain 7 or more C-terminal region, by designing and
      synthesizing DAP-BpB (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-(S)-phenylglycine-4
      (4-(8-biotinamido)octylamino)benzoyl)benzyl)methylamide), a photoactivable DAPT
      derivative. We also found that DAP-BpB selectively binds to the high molecular
      weight gamma-secretase complex in an activity-dependent manner. Photolabeling of
      PS by DAP-BpB is completely blocked by DAPT or its structural relatives (e.g.
      Compound E) as well as by arylsulfonamides. In contrast, transition-state
      analogue inhibitor L-685,458 or alpha-helical peptidic inhibitor attenuated the
      photolabeling of PS1 only at higher concentrations. These data illustrate the
      DAPT binding site as a novel functional domain within the PS C-terminal fragment
      that is distinct from the catalytic site or the substrate binding site.

PMID- 16569644
TI  - Cloning and recombinant expression of active full-length xylosyltransferase I (XT
      I) and characterization of subcellular localization of XT-I and XT-II.
AB  - Xylosyltransferase I (XT-I) catalyzes the transfer of xylose from UDP-xylose to
      serine residues in proteoglycan core proteins. This is the first and apparently
      rate-limiting step in the biosynthesis of the tetrasaccharide linkage region in
      glycosaminoglycan-containing proteoglycans. The XYLT-II gene codes for a highly
      homologous protein, but its physiological function is not yet known. Here we
      present for the first time the construction of a vector encoding the full-length
      GFP-tagged human XT-I and the recombinant expression of the active enzyme in
      mammalian cells. We expressed XT-I-GFP and various GFP-tagged XT-I and XT-II
      mutants with C-terminal truncations and deletions in HEK-293 and SaOS-2 cells in
      order to investigate the intracellular localization of XT-I and XT-II.
      Immunofluorescence analysis showed a distinct perinuclear pattern of XT-I-GFP and
      XT-II-GFP similar to that of alpha-mannosidase II, which is a known enzyme of the
      Golgi cisternae. Furthermore, a co-localization of native human XT-I and alpha
      mannosidase II could also be demonstrated in untransfected cells. Using brefeldin
      A, we could also show that both xylosyltransferases are resident in the early
      cisternae of the Golgi apparatus. For its complete Golgi retention, XT-I requires
      the N-terminal 214 amino acids. Unlike XT-I, for XT-II, the first 45 amino acids
      are sufficient to target and retain the GFP reporter in the Golgi compartment.
      Here we show evidence that the stem regions were indispensable for Golgi
      localization of XT-I and XT-II.

PMID- 16569645
TI  - Functional analysis of recombinant mutants of maxadilan with a PAC1 receptor
      expressing melanophore cell line.
AB  - Maxadilan, a 61-amino-acid vasodilatory peptide, was initially isolated from the
      salivary glands of the sand fly Lutzomyia longipalpis. Although its primary
      sequence has no homology to that of pituitary adenylate cyclase-activating
      peptide, maxadilan is an agonist for the PAC1 receptor. A total of 58
      substitution and deletion mutants was engineered in an effort to determine which
      residues were important for receptor activation. The mutants were characterized
      functionally using an assay based on pigment granule translocation in PAC1
      expressing Xenopus laevis melanophores. Substitution of charged residues and
      proline 43 could alter (but not eliminate) the agonist activity of the mutants.
      In contrast, we found that several multiple substitution mutants of the predicted
      beta-strand threonine residues became antagonists at the PAC1 receptor. The
      results suggest that these threonine residues are cooperatively involved in PAC1
      activation.

PMID- 16569646
TI  - The effect of population aging on future hospital demand.
AB  - This analysis examines how shifts in the age distribution of the U.S. population,
      reflecting both the aging of the baby-boom generation and increased longevity,
      will affect demand for hospital inpatient services during the next ten years.
      Over that period, aging will drive about 0.74 percent annual growth in use of
      services. Aging's effect on inpatient demand varies by medical condition, with
      the highest rates of growth in services most used by elderly patients. Even for
      those services, however, aging is a much less important factor than local
      population trends and changing practice patterns attributable to advancing
      medical technology.

PMID- 16569647
TI  - Microsatellite instability and methylation of the DNA mismatch repair genes in
      head and neck cancer.
AB  - BACKGROUND: Methylation in the promoter region of the DNA mismatch repair genes
      hMLH1 and hMSH2 and microsatellite instability at three loci were analyzed in the
      tumor tissue from patients with head and neck cancer. METHODS: Microsatellite
      instability and promoter methylation were investigated by PCR, denaturing
      polyacrylamide gel electrophoresis and digestion with methylation-specific
      restriction enzymes. RESULTS: Microsatellite instability was observed in 41% of
      the patients. hMLH1 and hMSH2 genes were methylated in 47% and 30% of the
      patients, respectively. BAT25 and BAT26 instability were associated with age and
      histopathology, respectively. Methylation frequency of the hMLH1 gene promoter
      was significantly higher in patients displaying a high level of microsatellite
      instability. Instability at the BAT 26 and D2S123 loci were associated with the
      MSI-high status. CONCLUSIONS: Our results indicate that microsatellite
      instability and modifications in the hMLH1 and hMSH2 genes are implicated in a
      significant proportion of the patients with head and neck cancer.

PMID- 16569648
TI  - Interleukin-2 continuous infusion and angiogenesis surrogate markers in
      metastatic renal cell carcinoma.

PMID- 16569649
TI  - ECG-gated multi-detector computed tomography for failure of conventional
      coronarography to detect intraluminal thrombus in saphenous vein graft.

PMID- 16569650
TI  - P2Y12 receptor antagonists: a rapidly expanding group of antiplatelet agents.

PMID- 16569651
TI  - Carcinoid heart disease as shown by 64-slice CT coronary angiography.

PMID- 16569652
TI  - Is the volume-outcome relation still an issue in the era of PCI with systematic
      stenting? Results of the greater Paris area PCI registry.
AB  - AIMS: In acute myocardial infarction (AMI), primary percutaneous transluminal
      angioplasty (PTCA) is the preferred option when it can be performed rapidly.
      Because of the limited access to high PTCA volume centres in some areas, it has
      been suggested that PTCA could be performed in low-volume centres on AMI
      patients. Little data exist on the validity of this strategy in modern era PTCA.
      METHODS AND RESULTS: The Greater Paris area comprises 11 million inhabitants and
      accounts for 18% of the French population. In 2001, the hospital agency of the
      Greater Paris area set up a registry of all PTCAs performed in this region. Data
      from 2001 and 2002 was analysed. Hospitals performing <400 PTCAs per year were
      classified as low-volume. A case-control analysis (propensity score) compared in
      hospital mortality in low- and high-volume centres. A total of 37 848 angioplasty
      procedures were performed in 44 centres during the study period; 24.7% were
      performed in low-volume centres. A non-statistically significant trend towards
      reduced in-hospital mortality was noted in high-volume centres as opposed to low
      volume centres: 2.01 vs. 2.42%, P = 0.057. In-hospital mortality rates were
      significantly different in the sub-group of emergency procedures: 6.75% in high-
      vs. 8.54% in low-volume centres, P = 0.028. No difference was noted between low-
      and high-volume centres in non-emergency procedures (0.62 vs. 0.62%, P = 0.99).
      CONCLUSION: In the era of modern stenting, a clear inverse relationship exists
      between hospital PTCA volume and in-hospital mortality after emergency
      procedures. Tolerance of low-volume thresholds for angioplasty centres with the
      purpose of providing primary PTCA in AMI should not be recommended, even in
      underserved areas.

PMID- 16569653
TI  - Early application of an implantable loop recorder allows effective specific
      therapy in patients with recurrent suspected neurally mediated syncope.
AB  - AIMS: This prospective multicentre observational study assessed the efficacy of
      specific therapy based on implantable loop recorder (ILR) diagnostic observations
      in patients with recurrent suspected neurally mediated syncope (NMS). METHODS AND
      RESULTS: Patients with three or more clinically severe syncopal episodes in the
      last 2 years without significant electrocardiographic and cardiac abnormalities
      were included. Orthostatic hypotension and carotid sinus syncope were excluded.
      After ILR implantation, patients were followed until the first documented syncope
      (Phase I). The ILR documentation of this episode determined the subsequent
      therapy and commenced Phase II follow-up. Among 392 patients, the 1-year
      recurrence rate of syncope during Phase I was 33%. One hundred and three patients
      had a documented episode and entered Phase II: 53 patients received specific
      therapy [47 a pacemaker because of asystole of a median 11.5 s duration and six
      anti-tachyarrhythmia therapy (catheter ablation: four, implantable defibrillator:
      one, anti-arrhythmic drug: one)] and the remaining 50 patients did not receive
      specific therapy. The 1-year recurrence rate in 53 patients assigned to a
      specific therapy was 10% (burden 0.07 +/- 0.2 episodes per patient/year) compared
      with 41% (burden 0.83 +/- 1.57 episodes per patient/year) in the patients without
      specific therapy (80% relative risk reduction for patients, P = 0.002, and 92%
      for burden, P = 0.002). The 1-year recurrence rate in patients with pacemakers
      was 5% (burden 0.05 +/- 0.15 episodes per patient/year). Severe trauma secondary
      to syncope relapse occurred in 2% and mild trauma in 4% of the patients.
      CONCLUSION: A strategy based on early diagnostic ILR application, with therapy
      delayed until documentation of syncope allows a safe, specific, and effective
      therapy in patients with NMS.

PMID- 16569654
TI  - Giant periprosthetic vegetation associated with pseudoaneurysmal-like rupture.

PMID- 16569655
TI  - Polymorphisms in estrogen bioactivation, detoxification and oxidative DNA base
      excision repair genes and prostate cancer risk.
AB  - To date, the potential impact of hormones on prostate cancer has predominantly
      focused on receptor-mediated events. However, catechol estrogens, if not
      inactivated by catechol-O-methyltransferase (COMT), can generate large quantities
      of reactive oxygen species (ROS). ROS may cause a spectrum of damage including
      oxidative DNA base lesions, which can lead to irreversible mutation(s) if they
      are not repaired by base excision repair (BER) systems. hOGG1 is a key enzyme in
      short patch BER because it recognizes and performs initial excision of the most
      common form of oxidative DNA base damage, 8-hydroxyguanine (8-oxo-dG). To
      investigate potential non-receptor-mediated estrogen effects, we evaluated the
      association between COMT Val158Met and hOGG1 Ser326Cys polymorphisms and prostate
      cancer in a family-based case-control study (439 prostate cancer cases, 479
      brother controls). We observed no noteworthy associations between these
      polymorphisms and prostate cancer risk in the total study population. However,
      among men with more aggressive prostate cancer, the hOGG1 326 Cys/Cys genotype
      was inversely associated with disease (OR=0.30; 95% CI=0.09-0.98). Combining the
      lower activity CYP1B1 432 Leu/Leu or Leu/Val genotypes (which may decrease the
      level of catechol estrogens and ROS generated) with the hOGG1 326 Cys/Cys
      genotype and the XRCC1 399 Arg/Arg or Arg/Gln genotypes (which may enhance BER)
      resulted in an even further reduced risk in Caucasians with more aggressive
      disease (OR=0.09; 95% CI=0.01-0.56). Including the high-activity COMT 158Val
      allele to this combination also lowered aggressive prostate cancer risk but the
      effect was not as strong (OR=0.20; 95% CI=0.05-0.88). The decreased risk we
      observed with the hOGG1 326 Cys/Cys genotype confirms an earlier report and the
      further reduced risk found with the CYP1B1 (432 Leu/Leu or Leu/Val)-hOGG1 (326
      Cys/Cys)-XRCC1 (Arg/Arg or Arg/Gln) genotype combination may lend new insights to
      the importance of ROS generated from non-receptor-mediated estrogenic mechanisms
      in more aggressive prostate cancer.

PMID- 16569656
TI  - H1 histamine receptor antagonists induce genotoxic and caspase-2-dependent
      apoptosis in human melanoma cells.
AB  - Previously, we found that the H1 histamine receptor antagonist diphenhydramine
      induces apoptosis in human acute T-lymphocytic leukemia cells. Since histamine
      has been shown to act as a growth factor in malignant melanoma cells, we decided
      to evaluate the in vitro effect of diphenhydramine and other H1 histamine
      receptor antagonists, such as terfenadine, astemizol and triprolidine on four
      malignant human melanoma cell lines. These antagonists were found to induce
      apoptotic cell death in all four melanoma cell lines. Apoptosis was determined by
      assessment of phosphatidylserine exposure on the surface of the cells and nuclear
      fragmentation. Importantly, H1 antagonist treatments did not adversely affect the
      viability of human melanocytes and murine fibroblasts at the same doses and
      duration of exposure. Treatment of melanoma cells with terfenadine induced DNA
      damage and caspases 2, 3, 6, 8 and 9 activation. Furthermore, the general caspase
      inhibitor (z-VAD-FMK) and a selective inhibitor of caspase-2 (z-VDVAD-FMK)
      protected melanoma cells from terfenadine-induced apoptosis. In contrast, the
      caspase-8 inhibitor (z-IETD-FMK) was ineffective. In addition, we found that
      mitochondria are involved in TEF-induced apoptosis, characterized by the
      dissipation of the mitochondrial transmembrane potential, the release of
      cytochrome c into the cytosolic compartment and caspase-9 activation. On the
      basis of these results we conclude that H1 histamine receptor antagonists induce
      apoptosis in human melanoma cells but not in normal melanocytes and embryonic
      murine fibroblasts; this apoptosis appears to be caspase-2-dependent and involves
      the mitochondrial pathway. The present results may contribute to the elaboration
      of novel therapeutic strategies for the treatment of malignant human melanoma.

PMID- 16569657
TI  - TRAF6 activation of PI 3-kinase-dependent cytoskeletal changes is cooperative
      with Ras and is mediated by an interaction with cytoplasmic Src.
AB  - Interleukin 1 (IL-1) has been implicated in the reorganization of the actin
      cytoskeleton. An expression vector encoding a PKB/Akt pleckstrin-homology domain
      fused to a fluorescent protein was used to detect phosphoinositide 3-kinase (PI 3
      kinase) products. It was observed that PI 3-kinase was activated either by
      treatment with IL-1 or by expression of either TRAF6, Src, MyD88 or dominant
      positive PI 3-kinase, and resulted in the formation of long filopodia-like
      cellular protrusions that appeared to branch at membrane sites consisting of
      clusters of phosphoinositide. This depended upon a TRAF6 polyproline motif and
      Src catalytic activity, and was blocked by inhibitors of PI 3-kinase, Src and
      Ras. Using both conventional and split fluorescent protein probes fused to
      expressed TRAF6 and Src in living cells, the polyproline sequence of TRAF6 and
      the Src-homology 3 (SH3) domain of Src were shown to be required for interaction
      between these two proteins. Interaction occurred within the cytoplasm, and not at
      either the cell membrane or cytoplasmic sequestosomes. In addition, co
      transfection of vectors expressing fluorescent-protein-fused TRAF6 and non
      fluorescent MyD88, IRAK1 and IRAK2 revealed an inverse correlation between
      increased sequestosome formation and activation of both PI 3-kinase and NF
      kappaB. Although a key factor in TRAF6-dependent activation of PI 3-kinase,
      ectopic expression of Src was insufficient for NF-kappaB activation and, in
      contrast to NF-kappaB, was not inhibited by IRAK2.

PMID- 16569658
TI  - Profilin-I-ligand interactions influence various aspects of neuronal
      differentiation.
AB  - Differentiating neurons extend membrane protrusions that develop into growing
      neurites. The driving force for neurite outgrowth is the dynamic actin
      cytoskeleton, which is regulated by actin-binding proteins. In this study, we
      describe for the first time, the role of profilin I and its ligand interactions
      in neuritogenesis of PC12 cells. High-level overexpression of wild-type profilin
      I had an inhibitory effect on neurite outgrowth. Low levels of profilin I did not
      disturb this process, but these cells developed many more filopodia along the
      neurite shafts. Low-level overexpression of mutant forms of profilin I changed
      one or more aspects of PC12 differentiation. Expression of a profilin I mutant
      that is defective in actin binding (profilin I(R74E)) decreased neurite length
      and strongly inhibited filopodia formation. Cells expressing mutants defective in
      binding proline-rich ligands (profilin I(W3A) and profilin I(R136D))
      differentiated faster, developed more and longer neurites and more branches. The
      profilin I(R136D) mutant, which is also defective in phosphatidylinositol 4,5
      bisphosphate binding, enhanced neurite outgrowth even in the absence of NGF.
      Parental PC12 cells treated with the ROCK inhibitor Y27632, differentiate faster
      and display longer neurites and more branches. Similar effects were seen in cells
      expressing profilin I(WT), profilin I(W3A) and profilin I(R74E). By contrast, the
      profilin I(R136D)-expressing cells were insensitive to the ROCK inhibitor,
      suggesting that regulation of profilin I by phosphatidylinositol 4,5-bisphosphate
      metabolism is crucial for proper neurite outgrowth. Taken together, our data show
      the importance of the interaction of profilin I with actin, proline-rich proteins
      and phosphatidylinositol 4,5-bisphosphate in neuronal differentiation of PC12
      cells.

PMID- 16569659
TI  - N-terminal palmitoylation within the appropriate amino acid environment conveys
      on NOS2 the ability to progress along the intracellular sorting pathways.
AB  - We have analysed the mechanism by which palmitoylation permits the progression of
      nitric oxide synthase 2 (NOS2) along the ER-Golgi-TGN pathway. Introduction of an
      additional myristoylation site at the N-terminus of NOS2 resulted in a chimera
      that displayed an enhanced association with the particulate fraction and with the
      plasma membrane but did not display increased enzymatic activity. In the absence
      of palmitoylation, introduction of a surrogate myristoylation site resulted in a
      mutant NOS2 with only 25% activity compared with the wild-type enzyme. Hence, the
      novel surrogate myristoyl moiety not only failed to increase NOS2 activity when
      introduced in a wild-type sequence environment, but was also unable to rescue the
      inactive phenotype of the Cys3Ser mutant. Introduction of an additional
      palmitoylatable Cys at position 2 of the wild-type sequence resulted in a chimera
      that associated to a larger degree with membranes and displayed decreased
      activity. Our data indicate that palmitoylation of inducible NOS at position 3
      exquisitely determines its transit along the secretory pathway following a route
      that cannot be mimicked by a surrogate myristoylation or by a palmitate at
      position 2. In addition, the exit of NOS2 from the TGN and the accumulation in
      the cellular plasma membrane per se did not correlate with increased .NO
      synthesis.

PMID- 16569660
TI  - NFATc1 nucleocytoplasmic shuttling is controlled by nerve activity in skeletal
      muscle.
AB  - Calcineurin-NFAT signaling has been shown to control activity-dependent muscle
      gene regulation and induce a program of gene expression typical of slow oxidative
      muscle fibers. Following Ca2+-calmodulin stimulation, calcineurin
      dephosphorylates NFAT proteins and induces their translocation into the nucleus.
      However, NFAT nuclear translocation has never been investigated in skeletal
      muscle in vivo. To determine whether NFATc1 nucleocytoplasmic shuttling depends
      on muscle activity, we transfected fast and slow mouse muscles with plasmids
      coding for an NFATc1-GFP fusion protein. We found that NFATc1-GFP has a
      predominantly cytoplasmic localization in the fast tibialis anterior muscle but a
      predominantly nuclear localization in the slow soleus muscle, with a
      characteristic focal intranuclear distribution. Two hours of complete inactivity,
      induced by denervation or anaesthesia, cause NFATc1 export out of the nucleus in
      soleus muscle fibers, whereas electrostimulation of tibialis anterior with a low
      frequency tonic impulse pattern, mimicking the firing pattern of slow motor
      neurons, causes NFATc1 nuclear translocation. The activity-dependent nuclear
      import and export of NFATc1 is a rapid event, as visualized directly in vivo by
      two-photon microscopy. The calcineurin inhibitor cain/cabin1 causes nuclear
      export of NFATc1 both in normal soleus and stimulated tibialis anterior muscle.
      These findings support the notion that in skeletal muscle NFATc1 is a calcineurin
      dependent nerve activity sensor.

PMID- 16569661
TI  - The aPKC-PAR-6-PAR-3 cell polarity complex localizes to the centrosome attracting
      body, a macroscopic cortical structure responsible for asymmetric divisions in
      the early ascidian embryo.
AB  - Posterior blastomeres of 8-cell stage ascidian embryos undergo a series of
      asymmetric divisions that generate cells of unequal sizes and segregate muscle
      from germ cell fates. These divisions are orchestrated by a macroscopic cortical
      structure, the ;centrosome attracting body' (CAB) which controls spindle
      positioning and distribution of mRNA determinants. The CAB is composed of a mass
      of cortical endoplasmic reticulum containing mRNAs (the cER-mRNA domain) and an
      electron dense matrix, but little is known about its precise structure and
      functions. We have examined the ascidian homologues of PAR proteins, known to
      regulate polarity in many cell types. We found that aPKC, PAR-6 and PAR-3
      proteins, but not their mRNAs, localize to the CAB during the series of
      asymmetric divisions. Surface particles rich in aPKC concentrate in the CAB at
      the level of cortical actin microfilaments and form a localized patch sandwiched
      between the plasma membrane and the cER-mRNA domain. Localization of aPKC to the
      CAB is dependent on actin but not microtubules. Both the aPKC layer and cER-mRNA
      domain adhere to cortical fragments prepared from 8-cell stage embryos. Astral
      microtubules emanating from the proximal centrosome contact the aPKC-rich
      cortical domain. Our observations indicate that asymmetric division involves the
      accumulation of the aPKC-PAR-6-PAR-3 complex at the cortical position beneath the
      pre-existing cER-mRNA domain.

PMID- 16569663
TI  - NMDA induces post-transcriptional regulation of alpha2-guanylyl-cyclase-subunit
      expression in cerebellar granule cells.
AB  - Activation of N-methyl-D-aspartate (NMDA) glutamate receptors commonly affects
      gene expression in different neurons. We reported previously that chronic
      treatment of rat cerebellar granule cells with NMDA (24 hours) upregulates the
      expression of mRNA encoding the alpha2 subunit of the nitric-oxide-sensitive
      guanylyl cyclase. However, the molecular mechanisms involved in this process
      remained to be elucidated. Here, we have performed mRNA-decay experiments using
      the transcriptional inhibitor actinomycin D, providing evidence that the half
      life of alpha2 mRNA is significantly prolonged in cells exposed to NMDA. The role
      of the 3' untranslated region of the alpha2 transcripts in NMDA-induced mRNA
      stabilisation was examined and an association between the RNA-binding proteins
      AUF1 and ELAV-like protein 1 (HuR/HuA), and endogenous alpha2 mRNA was
      demonstrated in vivo, as revealed by coimmunoprecipitation experiments with
      specific antibodies against AUF1 and HuR. Further studies indicated that
      stimulation of the NMDA receptor induces a downregulation in AUF1 levels
      stabilising the alpha2 mRNA transcripts. These events are triggered through a
      mechanism that depends on formation of nitric oxide, and on the subsequent
      activation of guanylyl cyclase and cGMP dependent protein kinases.

PMID- 16569662
TI  - Targeted wild-type and jerker espins reveal a novel, WH2-domain-dependent way to
      make actin bundles in cells.
AB  - The espin actin-bundling proteins, which are the target of deafness mutations,
      are present in the parallel actin bundles of stereocilia and microvilli and
      appear to increase their steady-state length. Here, we report a new activity of
      the espins, one that depends on their enigmatic WH2 domain: the ability to
      assemble a large actin bundle when targeted to a specific subcellular location.
      This activity was observed for wild-type espins targeted to the centrosome in
      transfected neuronal cells and for jerker espins targeted to the nucleolus in a
      wide variety of transfected cells as a result of the frameshifted peptide
      introduced into the espin C-terminus by the jerker deafness mutation. This
      activity, which appears specific to espins, requires two espin F-actin-binding
      sites and the actin-monomer-binding activity of the espin WH2 domain, but can be
      mimicked by adding a WH2 domain to an unrelated actin-bundling protein, villin.
      Espins do not activate the Arp2/3 complex in vitro, and bundle assembly is not
      indicative of in-vitro nucleation activity. Our results suggest a novel way to
      build actin bundles at specific sites in cells.

PMID- 16569664
TI  - Extracellular adenosine activates AMP-dependent protein kinase (AMPK).
AB  - Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric
      complex that senses intracellular energy status and exerts rapid regulation on
      energy-demanding and -consuming metabolic pathways. Although alterations in the
      intracellular adenosine nucleotide pool are traditionally assumed to be the
      consequence of changes in energy metabolism, in this study we have addressed the
      question of whether extracellular adenosine contributes to AMPK regulation. In
      the intestinal rat epithelial cell line IEC-6, addition of adenosine rapidly
      increases AMP intracellular concentrations and upregulates alpha1AMPK, thus
      promoting phosphorylation of its downstream target acetyl-CoA carboxylase (ACC).
      The effect of adenosine on AMPK signaling is completely blocked by transducing
      IEC-6 cells with an adenoviral vector expressing a mutated alpha1 subunit,
      resulting in a dominant-negative effect on endogenous AMPK activity. These
      effects are blocked by 5'-iodotubercidine (5'-ITU), an inhibitor of adenosine
      kinase. Moreover, inhibition of adenosine transport through the concentrative
      adenosine plasma membrane transporter CNT2 with formycin B results in the
      blockade of adenosine-mediated AMPK signaling. Extracellular adenosine is equally
      able to activate AMPK and promote ACC phosphorylation in liver parenchymal cell
      models in a manner that is also inhibited by 5'-ITU. In summary, this study shows
      that adenosine, when added at physiological concentrations, activates AMPK and
      promotes ACC phosphorylation. Adenosine must be transported and phosphorylated to
      exert its action. Thus, nucleoside transporters might be novel players in the
      complex regulation of AMPK and energy metabolism.

PMID- 16569666
TI  - Multiple factors contribute to integrin-talin interactions in vivo.
AB  - The cytoplasmic protein talin is an essential part of the integrin-cytoskeleton
      link. We characterized the interaction between integrin and two conserved regions
      of talin, the N-terminal ;head' domain and the C-terminus, which includes the
      I/LWEQ domain, within the living organism. Green-fluorescent-protein-tagged head
      and C-terminal domains were recruited to integrin adhesion sites. Both required
      integrins for recruitment, but the C-terminal domain also required endogenous
      talin, showing it was not recruited directly by integrins. We used chimeric
      transmembrane proteins containing the cytoplasmic domain of the integrin beta
      subunit to examine the integrin-talin head interaction. Monomeric chimeric
      proteins did not recruit talin head, whereas dimeric chimeras efficiently
      recruited it and caused a strong inhibition of integrin-mediated adhesion. These
      chimeras recruited surprisingly few integrin-associated proteins, indicating that
      recruitment of talin did not initiate a cascade of recruitment. Mutagenesis of
      the integrin cytoplasmic domain, within the chimera, showed the dominant-negative
      inhibition was not due to talin sequestration alone and that additional
      interactions are required.

PMID- 16569665
TI  - Twinfilin is an actin-filament-severing protein and promotes rapid turnover of
      actin structures in vivo.
AB  - Working in concert, multiple actin-binding proteins regulate the dynamic turnover
      of actin networks. Here, we define a novel function for the conserved actin
      binding protein twinfilin, which until now was thought to function primarily as a
      monomer-sequestering protein. We show that purified budding yeast twinfilin
      (Twf1) binds to and severs actin filaments in vitro at pH below 6.0 in bulk
      kinetic and fluorescence microscopy assays. Further, we use total internal
      reflection fluorescence (TIRF) microscopy to demonstrate that Twf1 severs
      individual actin filaments in real time. It has been shown that capping protein
      directly binds to Twf1 and is required for Twf1 localization to cortical actin
      patches in vivo. We demonstrate that capping protein directly inhibits the
      severing activity of Twf1, the first biochemical function ascribed to this
      interaction. In addition, phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2]
      inhibits Twf1 filament-severing activity. Consistent with these biochemical
      activities, a twf1Delta mutation causes reduced rates of cortical actin patch
      turnover in living cells. Together, our data suggest that twinfilin coordinates
      filament severing and monomer sequestering at sites of rapid actin turnover and
      is controlled by multiple regulatory inputs.

PMID- 16569667
TI  - Epithelial cell motility is triggered by activation of the EGF receptor through
      phosphatidic acid signaling.
AB  - Phospholipase D catalyzes the hydrolysis of phosphatidylcholine to generate
      phosphatidic acid, and there is currently much interest in elucidating messenger
      functions for this molecule. We report here that wounding sheets of corneal
      epithelial and Madin Darby canine kidney cells induces strong activation of
      phospholipase D, and we provide evidence that activation is amplified through a
      positive feed-back loop. Short-chain analogues of phosphatidic acid induce
      motility robustly in corneal and other epithelial cell types. The effects of
      these analogues were not the result of their conversion to the corresponding
      diacylglycerol or lysophosphatidic acid, implying that phosphatidic acid acts
      directly on one or more cellular targets. Strikingly, phosphatidic acid signaling
      was found to stimulate the epidermal growth factor receptor (EGFR) through a
      transactivation process. Healing of wounds in sheets of corneal epithelial cells
      is absolutely dependent on epidermal growth factor receptor signaling, and the
      present data suggest that its activation is a result of wound-induced
      phospholipase D activation.

PMID- 16569668
TI  - Dissecting the signaling and mechanical functions of the dystrophin-glycoprotein
      complex.
AB  - Duchenne muscular dystrophy is a severe disorder caused by mutations in the
      dystrophin gene. Dystrophin is required for assembly of the dystrophin
      glycoprotein complex and provides a mechanically strong link between the
      cytoskeleton and the extracellular matrix. Several proteins in the complex also
      participate in signaling cascades, but the relationship between these signaling
      and mechanical functions in the development of muscular dystrophy is unclear. To
      explore the mechanisms of myofiber necrosis in dystrophin-deficient muscle, we
      tested the hypothesis that restoration of this complex without a link to the
      cytoskeleton ameliorates dystrophic pathology. Transgenic mice were generated
      that express Dp116, a non-muscle isoform of dystrophin that assembles the
      dystrophin-glycoprotein complex, in muscles of dystrophin-deficient mdx(4cv)
      mice. However, the phenotype of these mice was more severe than in controls.
      Displacement of utrophin by Dp116 correlated with the severity of dystrophy in
      different muscle groups. Comparison with other transgenic lines demonstrated that
      parts of the dystrophin central rod domain were required to localize neuronal
      nitric oxide synthase to the sarcolemma, but this was not correlated with
      presence or extent of dystrophy. Our results suggest that mechanical
      destabilization, rather than signaling dysfunction, is the primary cause of
      myofiber necrosis in dystrophin-deficient muscle.

PMID- 16569669
TI  - Interaction of SH2-Bbeta with RET is involved in signaling of GDNF-induced
      neurite outgrowth.
AB  - RET receptor signalling is essential for glial-cell-line-derived neurotrophic
      factor (GDNF)-induced survival and differentiation of various neurons such as
      mesencephalic neurons. To identify proteins that mediate RET-dependent signaling,
      yeast two-hybrid screening was performed with the intracellular domain of RET as
      bait. We identified a new interaction between RET and the adapter protein SH2
      Bbeta. Upon GDNF stimulation of PC12-GFRalpha1-RET cells (that stably overexpress
      GDNF receptor alpha1 and RET), wild-type SH2-Bbeta co-immunoprecipitated with
      RET, whereas the dominant-negative SH2-Bbeta mutant R555E did not. RET interacted
      with endogenous SH2-Bbeta both in PC12-GFRalpha1-RET cells and in rat tissues.
      Mutagenesis analysis revealed that Tyr981 within the intracellular domain of RET
      was crucial for the interaction with SH2-Bbeta. Morphological evidence showed
      that SH2-Bbeta and RET colocalized in mesencephalic neurons. Furthermore,
      functional analysis indicated that overexpression of SH2-Bbeta facilitated GDNF
      induced neurite outgrowth in both PC12-GFRalpha1-RET cells and cultured
      mesencephalic neurons, whereas the mutant R555E inhibited the effect. Moreover,
      inhibition of SH2-Bbeta expression by RNA interference caused a significant
      decrease of GDNF-induced neuronal differentiation in PC12-GFRalpha1-RET cells.
      Taken together, our results suggest that SH2-Bbeta is a new signaling molecule
      involved in GDNF-induced neurite outgrowth.

PMID- 16569670
TI  - Increased frequency and broadened specificity of latent EBV nuclear antigen-1
      specific T cells in multiple sclerosis.
AB  - Epidemiological studies consistently demonstrate that patients with multiple
      sclerosis are almost universally infected with Epstein-Barr virus (EBV) and that
      the risk of developing the disease increases with the level of EBV-specific
      antibody titers. The EBV-encoded nuclear antigen-1 (EBNA1) maintains the viral
      episome in replicating infected human B cells, and EBNA1-specific CD4+ T cells
      have been identified as a crucial part of the EBV-specific immune control in
      healthy individuals. We studied 20 untreated EBV seropositive patients with
      multiple sclerosis and 20 healthy EBV carriers matched demographically and for
      the expression of multiple sclerosis-associated HLA-DR alleles for their
      immunological control of EBV latency at the level of EBNA1-specific T cells.
      Using 51 overlapping peptides covering the C-terminal of EBNA1 domain of EBNA1
      (amino acids 400-641), peptide-specific CD4+ memory T cells in patients with
      multiple sclerosis were found to be strikingly elevated in frequency, showed
      increased proliferative capacity and an enhanced interferon-gamma production. In
      contrast to EBNA1, T-cell responses to three other latent and three other lytic
      immunodominant EBV antigens and human cytomegalovirus (HCMV) epitopes did not
      differ between patients and controls, indicating a distinct role for EBNA1
      specific T-cell responses in multiple sclerosis. CD4+ T cells from healthy virus
      carriers preferentially recognized multiple epitopes within the centre part of
      the C-terminal, whereas the stimulatory epitopes in multiple sclerosis patients
      covered the entire sequence of this domain of EBNA1. Quantification of EBV viral
      loads in peripheral blood mononuclear cells (PBMC) by real-time polymerase chain
      reaction (PCR) showed higher levels of EBV copy numbers in some patients with
      multiple sclerosis, although the overall difference in viral loads was not
      statistically significant compared with healthy virus carriers. We suggest that
      the accumulation of highly antigen-sensitive EBNA1-specific Th1 cells in multiple
      sclerosis is capable of sustaining autoimmunity by cross-recognition of
      autoantigens or by TCR-independent bystander mechanisms.

PMID- 16569671
TI  - Brain and behaviour in children with 22q11.2 deletion syndrome: a volumetric and
      voxel-based morphometry MRI study.
AB  - In people with velo-cardio-facial syndrome [or 22q11.2 deletion syndrome
      (22qDS)], a single interstitial deletion of chromosome 22q11.2 causes a wide
      spectrum of cognitive deficits ranging from global learning difficulties to
      specific cognitive deficits. People with 22qDS are also at high risk of
      developing attention-deficit/hyperactivity disorder and autism spectrum disorders
      in childhood, and schizophrenia in adolescence or adult life. However, the
      neurobiology of 22qDS, and the relationship between abnormalities in brain
      anatomy and behaviour, is poorly understood. Thus, we studied the neuroanatomy of
      22qDS children using fully automated voxel-based morphometry (VBM) and manually
      traced single region-of-interest (ROI) analysis. Also, we investigated whether
      those brain regions that differed significantly between groups were related to
      behavioural differences within children with 22qDS. We compared the brain
      morphometry of 39 children and adolescents with 22qDS (mean age: 11 years, SD +/
      3, IQ = 67, SD +/-10) and 26 sibling controls (mean age: 11 years, SD +/-3, IQ =
      102, SD +/-12). Using VBM, we found, after correction for IQ, that individuals
      with 22qDS compared with controls had a significant reduction in cerebellar grey
      matter, and white matter reductions in the frontal lobe, cerebellum and internal
      capsule. Using single ROI analysis, we found that people with 22qDS had a
      significant (P < 0.05) reduction in bulk volume bilaterally in the occipital
      parietal lobes, but a larger right caudate nucleus and lateral ventricles.
      Further, within people with 22qDS, there was a significant positive correlation
      between severity of (i) schizotypy score and grey matter volume of the temporo
      occipital regions and the corpus striatum; (ii) emotional problems and grey
      matter volume of frontostriatal regions; and (iii) social behavioural
      difficulties and grey matter in frontostriatal regions. Thus, subjects with 22qDS
      have widespread changes in brain anatomy, particularly affecting white matter,
      basal ganglia and cerebellum. Also, within 22qDS, regionally specific differences
      in brain development may partially underpin behavioural differences. We suggest
      that there is preliminary evidence for specific vulnerability of the
      frontostriatal and cerebellar-cortical networks in 22qDS.

PMID- 16569672
TI  - Polymeric IgR knockout mice are more susceptible to mycobacterial infections in
      the respiratory tract than wild-type mice.
AB  - It is generally accepted that cellular, and not humoral immunity, plays the
      crucial role in defense against intracellular bacteria. However, accumulating
      data indicate the importance of humoral immunity for the defense against a number
      of intracellular bacteria, including mycobacteria. We have investigated the role
      of secretory IgA, the main isotype found in mucosal tissues, in protection
      against mycobacterial infection, using polymeric IgR (pIgR)-deficient mice.
      Characterization of the humoral response induced after intra-nasal immunizations
      with the mycobacterial antigen PstS-1 revealed a loss of antigen-specific IgA
      response in saliva from the knockout mice. IgA level in the bronchoalveolar
      lavage of knockout mice was similar to wild-type level, although the IgA
      antibodies must have reached the lumen by other means than pIgR-mediated
      transport. Infection with Mycobacterium bovis bacillus Calmette-Guerin (BCG)
      demonstrated that the immunized pIgR-/- mice were more susceptible to BCG
      infection than immunized wild-type mice, based on higher bacterial loads in the
      lungs. This was accompanied by a reduced production of both IFN-gamma and tumor
      necrosis factor-alpha (TNF-alpha) in the lungs. Additionally, the pIgR-/- mice
      displayed reduced natural resistance to mycobacterial infection proved by
      significantly higher bacterial growth in their lungs compared with wild-type mice
      after infection with virulent Mycobacterium tuberculosis. The knockout mice
      appeared to have a delayed mycobacteria-induced immune response with reduced
      expression of protective mediators, such as IFN-gamma, TNF-alpha, inducible
      nitric oxide synthase and regulated upon activation normal T cell sequence,
      during early infection. Collectively, our results show that actively secreted IgA
      plays a role in protection against mycobacterial infections in the respiratory
      tract, by blocking entrance of bacilli into the lungs, in addition to modulation
      of the mycobacteria-induced pro-inflammatory response.

PMID- 16569673
TI  - LIGHT is dispensable for CD4+ and CD8+ T cell and antibody responses to influenza
      A virus in mice.
AB  - The tumor necrosis factor family ligands, LIGHT (lymphotoxin like, exhibits
      inducible expression and competes with HSV glycoprotein D for HVEM, a receptor
      expressed by T lymphocytes), 4-1BBL and CD70, are found in the same gene cluster
      on mouse chromosome 17. Although the roles of 4-1BB-4-1BBL and CD27-CD70
      interactions in anti-viral T cell responses have been well established, the role
      of LIGHT in T cell activation/expansion in vivo is less clear. Under conditions
      that were previously employed to demonstrate a role for 4-1BBL in CD8+ T cell
      memory, wild-type and LIGHT-/- mice were infected with influenza A virus and
      primary and memory/recall responses were measured at various time points
      thereafter. Neither primary expansion nor memory/recall CD8+ T cell responses
      were affected by the absence of LIGHT, as measured up to 2 months post-infection.
      CD4+ T cell responses were also unaffected by LIGHT deficiency. Furthermore, we
      found that LIGHT played no role in the induction of influenza-specific IgG1 and
      IgG2a serum antibodies. Taken together, these data suggest that LIGHT is
      dispensable for the acquired immune response to influenza virus in mice with no
      effect on the induction, maintenance or reactivation of CD8+ T cell memory.

PMID- 16569674
TI  - A redundant role for PKC-epsilon in mast cell signaling and effector function.
AB  - Protein kinase (PK) C-epsilon is strongly expressed in mast cells (MCs) and
      activated in response to antigen-mediated high-affinity receptor for IgE (Fc
      epsilonR1) engagement. A critical role of PKC-epsilon in antigen-triggered
      activation of various signaling pathways was observed in basophilic leukemia
      cells. To study the function of PKC-epsilon in MCs differentiated in vitro from
      murine bone marrow, we used our established PKC-epsilon null mice. Unexpectedly,
      we did not reveal any difference in antigen-induced activation of many central
      signaling molecules (PKB, mitogen-activated protein kinase, p38, Jun-N-terminal
      kinase, phospholipase C-gamma1, Bruton's tyrosine kinase, PKD, Fos and PKC-delta)
      in time-course as well as dose-response studies between PKC-epsilon-deficient and
      wild-type MCs. In correlation, antigen-triggered degranulation, release of
      arachidonic acid and secretion of IL-6 were unaltered by the loss of PKC-epsilon.
      Furthermore, stimulation of MCs via different receptor systems [Steel factor
      receptor (c-kit) and toll-like receptor 4] did not lead to differences in the
      measured responses between both cell types. These results strongly suggest that
      PKC-epsilon plays a redundant role in MCs stimulated by antigen as well as other
      well-known MC stimuli.

PMID- 16569675
TI  - Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN.
AB  - CIRE/mDC-SIGN is a C-type lectin we originally identified as a molecule
      differentially expressed by mouse dendritic cell (DC) populations. Immunostaining
      with a CIRE/mDC-SIGN-specific mAb revealed that CIRE/mDC-SIGN is indeed on the
      surface of some CD4+, CD4- 8- DCs and plasmacytoid pre-DCs, but not on CD8+ DCs.
      It has been proposed that CIRE/mDC-SIGN is the functional orthologue of human DC
      SIGN (hDC-SIGN), a molecule that both enhances T cell responses and facilitates
      antigen uptake. We assessed if CIRE/mDC-SIGN and hDC-SIGN exhibit functional
      similarities. CIRE/mDC-SIGN is down-regulated upon activation, but unlike hDC
      SIGN, incubation with IL-4 and IL-13 did not enhance CIRE/mDC-SIGN expression,
      indicating differences in gene regulation. Like hDC-SIGN, CIRE/mDC-SIGN bound
      mannosylated residues. However, we could detect no role for CIRE/mDC-SIGN in T
      cell-DC interactions and the protein did not bind to pathogens known to interact
      with hDC-SIGN, including Leishmania mexicana, cytomegalovirus, HIV and lentiviral
      particles bearing the Ebolavirus glycoprotein. The binding of CIRE/mDC-SIGN to
      hDC-SIGN ligands was not rescued when CIRE/mDC-SIGN was engineered to express the
      stalk region of hDC-SIGN. We conclude that there are significant differences in
      the fine specificity of the C-type lectin domains of hDC-SIGN and CIRE/mDC-SIGN
      and that these two molecules may not be functional orthologues.

PMID- 16569676
TI  - The quantitative assessment of MHC II on thymic epithelium: implications in
      cortical thymocyte development.
AB  - The dynamics of MHC II expression in various thymic stromal compartments was
      investigated. By including MHC II in flow cytometry in addition to the cortical
      CDR1, medullary UEA-1 and pan-epithelial G8.8 markers, thymic stromal
      compartments were subdivided into at least six different populations. The total
      level of surface and cytoplasmic MHC II from fresh cortical thymic epithelial
      cells (cTECs) of normal mouse was as high as MHC II levels in medullary thymic
      epithelial cells (mTECs). MHC II levels as well as the percentages and cycling
      status of thymic epithelial cell populations expressing MHC II were not static
      during post-natal development, suggesting quantitative flexibility in presenting
      signals to the developing thymocytes. Although there was no evidence found for
      regulation of surface MHC II levels by TCR or by IFN-gamma, the absence of class
      II transactivator reduced both the level of MHC II expression and the number of
      MHC II+ cells. Surprisingly, MHC II molecules were found to form distinct focal
      aggregates on the surface of cTEC but not mTEC using high-resolution analysis by
      confocal microscopy. Moreover, these aggregates were formed independent of TCR or
      TCR-bearing cells in the thymus. These aggregates could potentially generate a
      functional unit containing a much higher local MHC II concentration to yield a
      higher avidity interaction. We discuss possible mechanisms for positive selection
      by weak interactions in the presence of such preformed MHC II aggregate units in
      cTEC.

PMID- 16569677
TI  - Activation of thymic T cells by MHC alloantigen requires syngeneic, activated
      CD4+ T cells and B cells as APC.
AB  - We examine here the in vitro requirements to activate immunocompetent T cells,
      present among thymocytes, to give rise to CTL, CD4+ T cells producing IL-2 and
      CD8+ T cells producing IFN-gamma. These thymocytes are naive in not having
      received antigen-dependent signals characteristic of the periphery. Their
      activation, upon stimulation with allogeneic spleen cells depleted of T cells,
      referred to here as allogeneic antigen-presenting cells (APCs), to produce allo
      MHC-specific effector T cells, requires activated (radiation resistant) CD4+ T
      cells, syngeneic with the responding thymocytes. We refer here to these T cells
      as 'help'. Furthermore, optimal T cell activation requires an Ig+ B220+ cell in
      the allogeneic APC population, most probably a B cell. The allogeneic APCs cannot
      be replaced by conventional bone marrow (BM)-derived dendritic cells (DCs)
      activated by CD40 ligation or exposure to LPS. The requirements for both help and
      allogeneic B cells in the activation of thymocytes contrast with the requirements
      to generate substantial responses from splenic T cell populations. Activated, BM
      derived DCs stimulate substantial splenic responses without help. These different
      requirements for activation could reflect the fact that thymocytes have not
      received an exit-thymus signal and/or that splenic T cells are heterogeneous,
      containing naive, memory and partially-activated T cells.

PMID- 16569678
TI  - New advances in coeliac disease: serum and intestinal expression of HLA-G.
AB  - Coeliac disease (CD) is a common autoimmune disorder characterized by an immune
      response to ingested gluten and has a strong HLA association with HLA-DQ2 and HLA
      DQ8, but as human HLA-DQ risk factors do not explain the entire genetic
      susceptibility to gluten intolerance. Our aim was to investigate whether HLA-G, a
      gene located in the MHC class I region, and with important role in the induction
      of immunotolerance, may contribute to CD susceptibility. We demonstrated the
      expression of soluble HLA-G (sHLA-G) forms in intestinal biopsy and in serum of
      patients with CD. Indeed, all patients tested showed a positive expression of HLA
      G in intestinal mucosa with different grade of immunoreaction. The serum levels
      of sHLA-G found in coeliac patients depend on the association with other diseases
      of autoimmune nature or genetics, and also depend on the transgressions in the
      diet with gluten ingested. The enhancer expression of sHLA-G in CD could be due
      as part of a mechanism to try restore the tolerance process towards oral antigens
      in a disease caused by loss of tolerance to dietary antigens and counteract the
      inflammation. In summary, in this paper, we demonstrate the association of CD
      with sHLA-G expression.

PMID- 16569679
TI  - IL-1beta, but not IL-1alpha, is required for antigen-specific T cell activation
      and the induction of local inflammation in the delayed-type hypersensitivity
      responses.
AB  - As IL-1 expression is augmented in delayed-type hypersensitivity (DTH) responses,
      we analyzed the role of IL-1 in this response. DTH responses against methyl BSA
      (mBSA) were significantly suppressed in IL-1beta-deficient (IL-1beta-/-) and IL
      1alpha/beta-/- mice, but not in IL-1alpha-/- mice. In contrast, responses in IL
      1R antagonist-/- (IL-1Ra-/-) mice were exacerbated. Lymph node cells derived from
      mBSA-sensitized IL-1beta-/-, IL-1alpha/beta-/- and IL-1R type I (IL-1RI)-/- mice,
      but not from IL-1alpha-/- mice, exhibited reduced proliferative responses against
      mBSA, while these from IL-1Ra-/- mice demonstrated augmented responses. DTH
      responses in wild-type mice following adoptive transfer of CD4+ T cells from mBSA
      sensitized IL-1alpha/beta-/- mice were also reduced, while those in mice given
      cells derived from IL-Ra-/- mice were increased. DTH responses in IL-1RI-/-, but
      not IL-1alpha/beta-/-, mice were reduced upon transplantation of mBSA-sensitized
      CD4+ T cells from wild-type mice. The recall response of mBSA-sensitized CD4+ T
      cells against mBSA decreased upon co-culture with dendritic cells (DCs) from IL
      1RI-/- mice, while the responses were normal with DCs from IL-1alpha/beta-/-
      mice. DTH responses in tumor necrosis factor alpha-/- (TNF-/-) mice were also
      suppressed; the magnitude of the suppression in IL-1alpha/beta-/-TNF-/- mice,
      however, was similar to that observed in IL-1alpha/beta-/- mice. These
      observations indicate that IL-1 possesses dual functions during the DTH response.
      IL-1beta is necessary for the efficient priming of T cells. In addition, CD4+ T
      cell-derived IL-1 plays an important role in the activation of DCs during the
      elicitation phase, resulting in the production of TNF, that activate allergen
      specific T cells.

PMID- 16569680
TI  - Thrombospondin orchestrates the tolerance-promoting properties of TGFbeta-treated
      antigen-presenting cells.
AB  - Eye-derived antigen-presenting cells (APCs) are known to contribute to the immune
      privilege status of the eye by inducing a form of peripheral tolerance that
      deviates T(h)1 type of pro-inflammatory immune responses. Similar systemic
      tolerance can also be induced by non-ocular APCs exposed to transforming growth
      factor beta (TGFbeta) in vitro. Such APCs were found to express enhanced levels
      of thrombospondin (TSP)-1, an extracellular matrix (ECM) protein. In this report,
      we analyzed the significance of TSP-1 in conferring tolerance-inducing properties
      on APCs. While TSP-treated APCs matched TGFbeta-treated APCs in their functional
      ability to induce systemic tolerance, a deficiency of TSP-1 or its receptor CD36
      prevented APCs from becoming tolerogenic in response to TGFbeta. Exogenous TSP-1
      restored tolerogenic ability of TGFbeta-treated TSP-1 null APCs. Both TGFbeta
      treated TSP-1 null and CD36 knockout APCs failed to inhibit IL-12 secretion.
      Furthermore, TGFbeta-treated TSP-1 null APCs, unlike similarly treated wild-type
      APCs, failed to increase secretion of active TGFbeta. Similar to TGFbeta, TSP
      could also up-regulate expression of MIP-2, TGFbeta2 and tumor necrosis factor
      alpha-all of which are required for tolerance induced by TGFbeta-treated APCs. We
      conclude that TSP-1, an ECM protein induced by TGFbeta treatment, orchestrates
      the changes in APC functional programs that equip these cells to promote
      tolerance of the eye-derived type.

PMID- 16569681
TI  - The ubiquitin-proteasome system plays essential roles in presenting an 8-mer CTL
      epitope expressed in APC to corresponding CD8+ T cells.
AB  - MUT1 is an H-2Kb-restricted 8-mer CTL epitope expressed in Lewis lung carcinoma
      (3LL) tumor cells derived from C57BL/6 (B6) mice. We constructed a chimeric gene
      encoding ubiquitin-fused MUT1 (pUB-MUT1). By using a gene gun, B6 mice were
      immunized with the gene prior to challenge with 3LL tumor cells. Tumor growth and
      lung metastasis were prominently suppressed in mice immunized with pUB-MUT1 but
      only slightly in those immunized with the MUT1 gene (pMUT) alone. CD8+ T cells
      were confirmed to be the final effector by in vitro experiments and in vivo
      removal of the cells with a corresponding antibody. Anti-tumor immunity was
      profoundly suppressed in mice deficient in an immuno-subunit of proteasome, LMP7.
      Furthermore, mice deficient in a proteasome regulator, PA28alpha/beta, failed to
      acquire protective immunity. Thus, application of the ubiquitin-fusion
      degradation pathway was useful even in immunization with genes encoding a single
      CTL epitope for induction of specific and active CD8+ T cells.

PMID- 16569682
TI  - c-Fos suppresses systemic inflammatory response to endotoxin.
AB  - We explored the role of the transcription factor c-Fos in lipopolysaccharide
      (LPS)-induced cytokine response using mice lacking c-Fos (Fos-/- mice). Compared
      with wild-type controls, Fos-/- macrophages and mice showed significantly
      enhanced production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and
      IL-12 p40, but reduced production of the anti-inflammatory cytokine IL-10.
      Bandshift analysis revealed that LPS-induced NF-kappaB binding activity to a
      functional site in the TNF-alpha promoter was significantly higher in Fos-/- than
      in wild-type macrophages. Using telemetry, we monitored body temperature and
      heart rate after LPS injection and found that Fos-/- mice undergo more severe
      hypothermia and bradycardia than wild-type mice. Such shock responses in Fos-/-
      mice were significantly reversed by neutralizing TNF-alpha. These data reveal a
      novel in vivo role for c-Fos as an anti-inflammatory transcription factor acting
      through suppression of NF-kappaB activity.

PMID- 16569683
TI  - Increased negative selection impairs neonatal B cell repertoire but does not
      directly lead to generation of disease-associated IgM auto-antibodies.
AB  - To determine if increased negative B cell selection, due to lowered signaling
      threshold of responsiveness to a ligand as a result of SHP-1 deficiency, during
      ontogeny leads to the origin of disease-associated IgM auto-antibodies (AAbs), 47
      V(H)J558+ VDJCmu rearrangements from SHP-1-deficient viable motheaten
      (me(v)/me(v)) and 24 J558+ VDJCmu rearrangements from normal me(v)/+ neonatal
      (<24 h post-birth) B cells were examined for their structural properties. None of
      the J558+ VDJCmu rearrangements from autoimmune-prone me(v)/me(v) had the
      characteristic CDR3H size restriction or arginine residues noted in disease
      associated IgM AAbs. However, the MVAR2/10 genes are expressed at a high
      frequency in me(v)/me(v) (31.9%) as compared with me(v)/+ (16.7%), and pM11 gene
      expression is exclusively (14.9%) noted in me(v)/me(v) B cells. Clearly, there is
      a trend toward higher expression of pM11 genes (P-value < or = 0.09) in
      autoimmune-prone me(v)/me(v) strain. The CDR2H region of J558+ VDJCmu
      recombinations from me(v)/me(v) has increased hotspot triplets predisposing to
      mutations as compared with me(v)/+ (P-value < or = 0.01) mice. A higher DFL D
      gene expression is noted in J558+ VDJCmu rearrangements from me(v)/me(v) (P-value
      < or = 0.1) in contrast to me(v)/+. The sophisticated logistic regression and
      odds ratio analysis of V-, D- and J-gene expressions in neonatal B cells from
      me(v)/me(v) and me(v)/+ mice demonstrates differential composition of the germ
      line IgM repertoire as a result of SHP-1 deficiency. These observations suggest
      that increased negative B cell selection during ontogeny impairs the developing
      IgM antibody repertoire but does not directly lead to generation of disease
      associated IgM AAbs.

PMID- 16569684
TI  - Increased urinary type II collagen helical and C telopeptide levels are
      independently associated with a rapidly destructive hip osteoarthritis.
AB  - OBJECTIVES: Biochemical markers reflecting the degradation of the type II
      collagen helical (Helix-II) and type II collagen C telopeptides (CTX-II) have
      been developed. AIM: To investigate the association of rapidly destructive hip
      osteoarthritis with urinary Helix-II and urinary CTX-II. PATIENTS AND METHODS: 12
      patients (mean age 70 years) meeting the criteria for rapidly destructive hip
      osteoarthritis and 28 patients with slowly progressive hip osteoarthritis (mean
      age 63 years) defined as <0.20 mm joint space loss/year were included in a case
      control study. In each patient, urinary Helix-II and CTX-II were measured at the
      end of the follow-up period, with retrospective evaluation of x rays. RESULTS:
      Helix-II levels were 41% (p = 0.002) higher in the 40 patients with hip
      osteoarthritis than in 75 healthy controls. Increased Helix-II levels were
      associated with decreased minimum joint space width of the hip (r = -0.57, p =
      0.001). Mean urinary Helix-II levels were 71% higher in rapidly destructive than
      in slowly progressive disease (mean (standard deviation (SD)) ng/mmol Cr: 396
      (160) v 232 (118) ng/mmol; p = 0.002). When levels of Helix-II and CTX-II in the
      highest tertile were both included in a multivariate logistic regression model,
      high Helix-II level (OR; (95% CI) 5.73 (1.01 to 32.8)) after adjustment for age
      and body mass index and high CTX-II level (6.67 (1.14 to 39.0)) were,
      independently of each other, associated with a rapidly destructive disease.
      CONCLUSION: Increased urinary Helix-II levels are associated with rapidly
      destructive hip osteoarthritis, independently of urinary CTX-II. Measurement of
      Helix-II, alone or in combination with CTX-II, could be useful for the clinical
      investigation of patients with hip osteoarthritis.

PMID- 16569685
TI  - Serum immunoglobulin free light chain assessment in rheumatoid arthritis and
      primary Sjogren's syndrome.
AB  - BACKGROUND: B cell activation may result in an increased secretion of
      immunoglobulin free light chains (FLCs) in autoimmune diseases. OBJECTIVE: To
      analyse serum FLC levels in patients with rheumatoid arthritis and in those with
      primary Sjogren's syndrome (pSS). PATIENTS AND METHODS: Blood samples were
      collected from 80 healthy blood donors, 50 patients with rheumatoid arthritis and
      139 patients with pSS. Serum FLC level was measured using a new quantitative
      immunoassay. RESULTS: Mean (standard error (SE)) serum kappa and lambda FLC
      levels were significantly higher in patients with rheumatoid arthritis and in
      those with pSS than in controls (kappa : 18.9 (1.1) and 16.3 (1.4) v 10.5 (0.4)
      mg/l, p<0.001 and p = 0.001, respectively; lambda: 16.7 (1.2) and 19.3 (1.5) v
      11.6 (0.6) mg/l, p<0.001 for both). 18 (36%) patients with rheumatoid arthritis
      and 31 (22.3%) patients with pSS had abnormal serum FLC levels (increased kappa
      or lambda levels and abnormal ratio of kappa:lambda). Serum kappa and lambda
      levels were correlated with other B cell activation markers in both diseases. FLC
      levels increased with disease activity, because, unlike total gammaglobulin and
      immunoglobulin G levels, they were significantly correlated with Disease Activity
      Score 28 in patients with rheumatoid arthritis (p = 0.004 for kappa, p = 0.05 for
      lambda) and with extraglandular involvement in pSS (p = 0.01 for kappa, p = 0.04
      for lambda). CONCLUSION: FLC levels are increased and correlate with disease
      activity in patients with rheumatoid arthritis and in those with pSS, two
      diseases in which increased risk of lymphoma could result from persistent B cell
      activation and disease activity. Further studies are required to determine
      whether FLC assessment could represent a relevant biomarker for response to
      treatment (especially B cell depletion) and for the risk of lymphoma in
      autoimmune diseases.

PMID- 16569686
TI  - Genetic characterisation of spontaneous ankylosing arthropathy with unique
      inheritance from Fas-deficient strains of mice.
AB  - BACKGROUND: The spontaneous onset of macroscopic arthropathy in the ankle of the
      particular F1 mice descended from two Fas-deficient strains of mice; a mutant
      substrain of MRL/Mp.Fas(lpr) (MRL/rpl) and C3H/He.Fas(lpr) (C3H/lpr) was recently
      observed. AIM: To histopathologically characterise and genetically interpret the
      unique inheritance mode of disease in this arthropathy model. METHODS: MRL/rpl,
      C3H/lpr, (MRL/rpl x C3H/lpr; MC) F1, (C3H/lpr x MRL/rpl; CM) F1 and MCF2 mice
      were bred under specific pathogen-free conditions. Histopathological grade of
      arthropathy was determined at 6 months by examination under a light microscope.
      To search for a linkage locus to the arthropathy, the whole genome of selected 48
      male MCF2 mice with 71 polymorphic microsatellite markers was scanned, followed
      by quantitative trait locus analysis. RESULTS: The incidence of microscopically
      defined arthropathy in the male and female MCF1 groups was 100% and 19.4%,
      respectively. No incidence was observed in the parental strains, MRL/rpl and
      C3H/lpr, and in CMF1 mice. In the MCF1 mice, the arthropathy mainly affected the
      ankle joints and was histopathologically characterised by marked entheseal
      proliferation with chondrocytic differentiation and ossification in the ankle
      joints, the manifestations similar to ankylosing enthesitis reported previously.
      An MRL/rpl-derived autosomal dominant susceptibility locus was mapped in the
      distal of D7Mit68 (60 cM) to the ankylosis onset. CONCLUSION: The MCF1 mice
      stably develop spontaneous ankylosing disorders in the ankle, with a male
      predominance. The unique inheritance mode of ankylosis is possibly interpreted by
      the genetic interaction between the autosomal dominant locus and a Y-linked
      locus.

PMID- 16569687
TI  - Clinical significance of P46L and R92Q substitutions in the tumour necrosis
      factor superfamily 1A gene.
AB  - OBJECTIVE: Tumour necrosis factor receptor-associated periodic syndrome (TRAPS)
      has been associated with several mutations in the TNF receptor super family 1A
      (TNFRSF1A), including most cysteine substitutions. However, the nature of two
      substitutions, P46L and R92Q, remains a topic of discussion. The aim of this
      study was to assess the actual role of these two sequence variations in a series
      of patients with TRAPS. METHODS: The main clinical data of 89 patients with TRAPS
      have been prospectively registered on a standard form. 84 patients or members of
      families with recurrent episodes of inflammatory symptoms spanning a period of
      more than 6 months and harbouring a TNFRSF1A mutation were studied. Clinical data
      have been analysed according to the nature of the mutation-P46L, R92Q or others.
      RESULTS: P46L is often seen in patients from Maghreb and is associated with a
      mild phenotype. P46L appears as a polymorphism with a non-specific role in
      inflammation. R92Q is associated with a variable phenotype and presents as a low
      penetrance mutation. Interpreting these results will require a comparison with
      clinical signs and genetic background.

PMID- 16569689
TI  - Torsion of the testicular appendix: importance of associated acute inflammation.
AB  - BACKGROUND: Torsion of the testicular appendix is the commonest cause of acute
      scrotum in children. The histological picture of these cases is variable and many
      show a heavy acute inflammatory cell infiltrate, unlike the response to pure
      ischaemic necrosis in other organs. The clinical implications and consequences of
      this associated inflammation are not clear. METHODS: A retrospective review of
      all cases presenting with torsion of the testicular appendix between 1987 and
      2005 was carried out. In all, 79 cases were reviewed and the degree of acute
      inflammatory cell infiltrate and other morphological parameters were assessed and
      compared with the patients' clinical, operative and postoperative findings.
      Stains for bacteria and fungi were examined. RESULTS: A positive correlation was
      found between the severity of acute inflammatory cell infiltrates and the longer
      duration of symptoms and presence of clinical evidence of torsion of the
      testicular appendages. No other association was detected between the pattern or
      degree of acute inflammatory cell infiltrate and any other clinicopathological
      variable that may indicate pyogenic infection. No bacteria or fungal elements
      were identified. Marked lymphatic dilation may be the only histological finding
      to indicate the presence of early torsion in cases of scrotal pain secondary to
      torsion of the appendix testis. CONCLUSION: Heavy acute inflammatory cell
      infiltrates in the torted testicular appendix can be regarded as marker of
      progression of this condition. Investigation for infection is therefore not
      necessary in such cases.

PMID- 16569688
TI  - Antiendothelial cell antibodies in vasculitis and connective tissue disease.
AB  - Antiendothelial cell antibodies (AECA) are a heterogeneous family of antibodies
      reacting with endothelial cell antigens. These antibodies are found in various
      diseases and recognise several antigen determinants. Different pathophysiological
      effects have been observed in in vitro experiments, which include direct or
      indirect cytotoxicity and endothelial cell apoptosis. Furthermore, some AECA
      activate endothelial cells, resulting in increased leucocyte adhesiveness,
      activation of coagulation and vascular thrombosis. In animal models, it has been
      shown that AECA could promote vascular damage. Neither the endothelial cell
      antigens nor their precise role in the pathogenecity of different diseases in
      which AECA are found is well characterised. Nowadays, it is not known whether
      AECA are an epiphenomenon accompanying vascular injury or whether they are
      pathogenic. It is controversial whether fluctuations in AECA titres are
      associated with disease activity during follow-up studies. This review summarises
      the present knowledge about AECA, AECA antigens and their potential role in the
      pathogenecity of vasculitis and connective tissue diseases.

PMID- 16569690
TI  - Comparative genomic hybridisation in malignant deciduoid mesothelioma.
AB  - BACKGROUND: Malignant deciduoid mesothelioma is a rare variant of epithelioid
      mesothelioma. This tumour generally has poor prognosis, and can be asbestos
      related. AIM: To identify peculiar genetic changes responsible for critical
      phases in pathogenesis of malignant deciduoid mesothelioma and their prognostic
      relevance. METHODS: Comparative genomic hybridisation was carried out in six
      cases of malignant pleural deciduoid mesothelioma, four sporadic and two
      familial. All cases were found to be asbestos related. Four patients died during
      follow-up and the mean survival was 29.5 (SD 14.2, range 12-43) months. RESULTS:
      Genetic abnormalities were found in all the tumour tissues, the most frequent
      being chromosomal gains at 1p, 12q, 17, 8q, 19 and 20 and losses at 13q, 6q and
      9p. Survival was found to be longer in those patients who presented a smaller
      number of losses (< or =2) in the tumorous chromosomes. CONCLUSIONS: Although
      numerous genetic changes are presented by deciduoid mesotheliomas, certain
      chromosomal regions are preferentially affected. The clinical outcome for this
      mesothelioma subtype is predicted by the number of losses.

PMID- 16569691
TI  - Phylogenetic fate mapping.
AB  - Cell fate maps describe how the sequence of cell division, migration, and
      apoptosis transform a zygote into an adult. Yet, it is only in Caenorhabditis
      elegans where microscopic observation of each cell division has allowed for
      construction of a complete fate map. More complex, and opaque, animals prove less
      yielding. DNA replication, however, generates somatic mutations. Consequently,
      multicellular organisms comprise mosaics where most cells acquire unique genomes
      that are potentially capable of delineating their ancestry. Here we take a
      phylogenetic approach to passively retrace embryonic relationships by deducing
      the order in which mutations have arisen during development. We show that
      polyguanine repeat DNA sequences are particularly useful genetic markers, because
      they frequently change length during mitosis. To demonstrate feasibility, we
      phylogenetically reconstruct the lineage of cultured mouse NIH 3T3 cells based on
      mutations affecting the length of polyguanine markers. We then employ whole
      genome amplification to genotype polyguanine markers in single cells taken from a
      mouse and use phylogenetics to infer the developmental relationships of the
      sampled tissues. The result is consistent with the present understanding of
      embryogenesis and demonstrates the large scale potential of this method for
      producing a complete mammalian cell fate at the resolution of a single cell.

PMID- 16569692
TI  - FRA1 is a determinant for the difference in RAS-induced transformation between
      human and rat fibroblasts.
AB  - Human diploid fibroblasts (HDF) immortalized by hTERT and simian virus 40 (SV40)
      early region (ER) exhibit a limited degree of transformation upon the expression
      of activated H-RAS (H-RAS V12) compared with rat embryonic fibroblasts (REF)
      immortalized by SV40 ER. Here, we identified FRA1 as a determinant for this
      difference in RAS-induced transformation. FRA1 was not induced by H-RAS V12 in
      the immortalized HDF, in contrast to its marked accumulation in the immortalized
      REF. Ectopic expression of FRA1 significantly enhanced anchorage-independent
      growth of various HDF expressing hTERT, SV40 ER, and H-RAS V12. More importantly,
      FRA1 could induce anchorage-independent growth as well as nude mice tumor
      formation of the immortalized HDF in the absence of H-RAS V12. The results of an
      in vitro kinase assay clearly showed that the RAS-induced extracellular signal
      regulated kinase (ERK) activation, which is responsible for FRA1 induction, was
      markedly attenuated in the HDF compared with that in the REF, despite no obvious
      differences in the phosphorylation status of ERK between the species. Our results
      strongly suggest that HDF negatively regulate the mitogen-activated protein
      kinase kinase (MEK)/ERK pathway more efficiently than REF, and consequently
      express less malignant phenotypes in response to H-RAS V12.

PMID- 16569693
TI  - Molecular evidence for two-stage learning and partial laterality in eyeblink
      conditioning of mice.
AB  - The anterior interpositus nucleus (AIN) is the proposed site of memory formation
      of eyeblink conditioning. A large part of the underlying molecular events,
      however, remain unknown. To elucidate the molecular mechanisms, we examined
      transcriptional changes in the AIN of mice trained with delay eyeblink
      conditioning using microarray, quantitative real-time RT-PCR, and in situ
      hybridization techniques. Microarray analyses suggested that transcriptionally up
      regulated gene sets were largely different between early (3-d training) and late
      (7-d) stages. Quantitative real-time RT-PCR aided by laser microdissection
      indicated that the expression of representative EARLY genes (Sgk, IkBa, and
      Plekhf1) peaked at 1-d training in both the paired and unpaired conditioning
      groups, and was maintained at a higher level in the paired group than in the
      unpaired group after 3-d training. In situ hybridization revealed increased
      expression of these genes in broad cerebellar areas, including the AIN, with no
      hemispheric preferences. In contrast, the expression of representative LATE genes
      (Vamp1, Camk2d, and Prkcd) was selectively increased in the AIN of the 7-d paired
      group, with dominance in the ipsilateral AIN. Increased Vamp1 mRNA expression was
      restricted to the ipsilateral dorsolateral hump, a subregion of the AIN. These
      expression patterns of two distinct subsets of genes fit well with the two-stage
      learning theory, which proposes emotional and motor learning phases, and support
      the notion that AIN has a crucial role in memory formation of eyeblink
      conditioning.

PMID- 16569694
TI  - A high-resolution map of transcription in the yeast genome.
AB  - There is abundant transcription from eukaryotic genomes unaccounted for by
      protein coding genes. A high-resolution genome-wide survey of transcription in a
      well annotated genome will help relate transcriptional complexity to function. By
      quantifying RNA expression on both strands of the complete genome of
      Saccharomyces cerevisiae using a high-density oligonucleotide tiling array, this
      study identifies the boundary, structure, and level of coding and noncoding
      transcripts. A total of 85% of the genome is expressed in rich media. Apart from
      expected transcripts, we found operon-like transcripts, transcripts from
      neighboring genes not separated by intergenic regions, and genes with complex
      transcriptional architecture where different parts of the same gene are expressed
      at different levels. We mapped the positions of 3' and 5' UTRs of coding genes
      and identified hundreds of RNA transcripts distinct from annotated genes. These
      nonannotated transcripts, on average, have lower sequence conservation and lower
      rates of deletion phenotype than protein coding genes. Many other transcripts
      overlap known genes in antisense orientation, and for these pairs global
      correlations were discovered: UTR lengths correlated with gene function,
      localization, and requirements for regulation; antisense transcripts overlapped
      3' UTRs more than 5' UTRs; UTRs with overlapping antisense tended to be longer;
      and the presence of antisense associated with gene function. These findings may
      suggest a regulatory role of antisense transcription in S. cerevisiae. Moreover,
      the data show that even this well studied genome has transcriptional complexity
      far beyond current annotation.

PMID- 16569695
TI  - The evolutionary diversification of cyanobacteria: molecular-phylogenetic and
      paleontological perspectives.
AB  - Cyanobacteria have played a significant role in Earth history as primary
      producers and the ultimate source of atmospheric oxygen. To date, however, how
      and when the group diversified has remained unclear. Here, we combine molecular
      phylogenetic and paleontological studies to elucidate the pattern and timing of
      early cyanobacterial diversification. 16S rRNA, rbcL, and hetR genes were
      sequenced from 20 cyanobacterial strains distributed among 16 genera, with
      particular care taken to represent the known diversity of filamentous taxa.
      Unlike most other bacteria, some filamentous cyanobacteria evolved a degree of
      cell differentiation, producing both specialized cells for nitrogen fixation
      (heterocysts) and resting cells able to endure environmental stress (akinetes).
      Phylogenetic analyses support the hypothesis that cyanobacteria capable of cell
      differentiation are monophyletic, and the geological record provides both upper
      and lower bounds on the origin of this clade. Fossil akinetes have been
      identified in 1,650- to 1,400-mega-annum (Ma) cherts from Siberia, China, and
      Australia, and what may be the earliest known akinetes are preserved in
      approximately 2,100-Ma chert from West Africa. Geochemical evidence suggests that
      oxygen first reached levels that would compromise nitrogen fixation (and hence
      select for heterocyst differentiation) 2,450-2,320 Ma. Integrating phylogenetic
      analyses and geological data, we suggest that the clade of cyanobacteria marked
      by cell differentiation diverged once between 2,450 and 2,100 Ma, providing an
      internal bacterial calibration point for studies of molecular evolution in early
      organisms.

PMID- 16569696
TI  - Evolution of cis elements in the differential expression of two Hoxa2
      coparalogous genes in pufferfish (Takifugu rubripes).
AB  - Sequence divergence in cis-regulatory elements is an important mechanism
      contributing to functional diversity of genes during evolution. Gene duplication
      and divergence provide an opportunity for selectively preserving initial
      functions and evolving new activities. Many vertebrates have 39 Hox genes
      organized into four clusters (Hoxa-Hoxd); however, some ray-finned fishes have
      extra Hox clusters. There is a single Hoxa2 gene in most vertebrates, whereas
      fugu (Takifugu rubripes) and medaka (Oryzias latipes) have two coparalogous genes
      [Hoxa2(a) and Hoxa2(b)]. In the hindbrain, both genes are expressed in rhombomere
      (r) 2, but only Hoxa2(b) is expressed in r3, r4, and r5. Multiple regulatory
      modules directing segmental expression of chicken and mouse Hoxa2 genes have been
      identified, and each module is composed of a series of discrete elements. We used
      these modules to investigate the basis of differential expression of duplicated
      Hoxa2 genes, as a model for understanding the divergence of cis-regulatory
      elements. Therefore, we cloned putative regulatory regions of the fugu and medaka
      Hoxa2(a) and -(b) genes and assayed their activity. We found that these modules
      direct reporter expression in a chicken assay, in a manner corresponding to their
      endogenous expression pattern in fugu. Although sequence comparisons reveal many
      differences between the two coparalogous genes, specific subtle changes in seven
      cis elements of the Hoxa2(a) gene restore segmental regulatory activity.
      Therefore, drift in subsets of the elements in the regulatory modules is
      responsible for the differential expression of the two coparalogous genes, thus
      providing insight into the evolution of cis elements.

PMID- 16569697
TI  - Chlorella virus MT325 encodes water and potassium channels that interact
      synergistically.
AB  - Fast and selective transport of water through cell membranes is facilitated by
      water channels. Water channels belonging to the major intrinsic proteins (MIPs)
      family have been found in all three domains of life, Archaea, Bacteria, and
      Eukarya. Here we show that Chlorella virus MT325 has a water channel gene, aqpv1,
      that forms a functional aquaglyceroporin in oocytes. aqpv1 is transcribed during
      infection together with MT325 kcv, a gene encoding a previously undescribed type
      of viral potassium channel. Coexpression of AQPV1 and MT325-Kcv in Xenopus
      oocytes synergistically increases water transport, suggesting a possible
      concerted action of the two channels in the infection cycle. The two channels
      operate by a thermodynamically coupled mechanism that simultaneously alters water
      conductance and driving force for water movement. Considering the universal role
      of osmosis, this mechanism is relevant to any cell coexpressing water and
      potassium channels and could have pathological as well as basic physiological
      relevance.

PMID- 16569698
TI  - Neural mechanisms of genetic risk for impulsivity and violence in humans.
AB  - Neurobiological factors contributing to violence in humans remain poorly
      understood. One approach to this question is examining allelic variation in the X
      linked monoamine oxidase A (MAOA) gene, previously associated with impulsive
      aggression in animals and humans. Here, we have studied the impact of a common
      functional polymorphism in MAOA on brain structure and function assessed with MRI
      in a large sample of healthy human volunteers. We show that the low expression
      variant, associated with increased risk of violent behavior, predicted pronounced
      limbic volume reductions and hyperresponsive amygdala during emotional arousal,
      with diminished reactivity of regulatory prefrontal regions, compared with the
      high expression allele. In men, the low expression allele is also associated with
      changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during
      aversive recall, and impaired cingulate activation during cognitive inhibition.
      Our data identify differences in limbic circuitry for emotion regulation and
      cognitive control that may be involved in the association of MAOA with impulsive
      aggression, suggest neural systems-level effects of X-inactivation in human
      brain, and point toward potential targets for a biological approach toward
      violence.

PMID- 16569699
TI  - Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer
      cell lines.
AB  - Interactions between neoplastic and stromal cells contribute to tumor
      progression. Wnt genes, involved in cell migration and often deregulated in
      cancers, are attractive candidates to regulate these effects. We have recently
      shown that coculture of breast cancer cells with macrophages enhances
      invasiveness via matrix metalloproteases and TNF-alpha. Here we demonstrate that
      coculture of MCF-7 cells and macrophages leads to up-regulation of Wnt 5a in the
      latter. This was accompanied by activation of AP-1/c-Jun in MCF-7. Recombinant
      Wnt 5a mimicked the coculture effect. Wnt 5a was also detectable in tumor
      associated macrophages in primary breast cancers. Experiments with agonists and
      antagonists of Wnt signaling revealed that a functional canonical pathway in the
      tumor cells was a necessary prerequisite; however, noncanonical signaling via Wnt
      5a and the Jun-N-terminal kinase pathway was critical for invasiveness. It was
      also responsible for induction of matrix metalloprotease-7, known to release TNF
      alpha. All these effects could be antagonized by dickkopf-1. Our results indicate
      that Wnt 5a is essential for macrophage-induced invasiveness, because it
      regulates tumor cell migration as well as proteolytic activity of the
      macrophages. The function of Wnt 5a as either a suppressor or promoter of
      malignant progression seems to be modulated by intercellular interactions. Wnt 5a
      detection in tumor-associated macrophages in breast cancer biopsies supports the
      assumption that similar events play a role in vivo.

PMID- 16569700
TI  - Messages diffuse faster than messengers.
AB  - In many cell-signaling pathways, information is transmitted by the diffusion of
      messenger molecules. Diffusion coefficients characterize the messenger's spatial
      range and the characteristic times of signal propagation. Inside cells, particles
      usually diffuse in the presence of immobile binding sites (or traps). It is well
      known that binding to traps results in an effective diffusion coefficient that is
      smaller than the free coefficient in media free of traps. To measure effective
      diffusion coefficients in cells, "tagged" particles are often used. Radioactive
      calcium was used in a giant squid axon and in cytosolic extracts of Xenopus
      laevis oocytes. Fluorescence recovery after photobleaching yields diffusion
      coefficients from observations of the distribution of fluorescently labeled
      proteins. In the absence of traps, free diffusion coefficients give both the rate
      at which single-particle mean square displacements increase and the rate at which
      information in the form of inhomogeneities in particle concentration spread out
      with time. We show here that, in the presence of traps, information diffuses
      faster than single particles. Thus, messages diffuse faster than messengers.
      Tagged-particle experiments give the single-particle diffusion coefficients and,
      thus, can underestimate the rate of diffusive signal propagation.

PMID- 16569701
TI  - Virulence of Leishmania major in macrophages and mice requires the gluconeogenic
      enzyme fructose-1,6-bisphosphatase.
AB  - Leishmania are protozoan parasites that replicate within mature phagolysosomes of
      mammalian macrophages. To define the biochemical composition of the phagosome and
      carbon source requirements of intracellular stages of L. major, we investigated
      the role and requirement for the gluconeogenic enzyme fructose-1,6-bisphosphatase
      (FBP). L. major FBP was constitutively expressed in both extracellular and
      intracellular stages and was primarily targeted to glycosomes, modified
      peroxisomes that also contain glycolytic enzymes. A L. major FBP-null mutant was
      unable to grow in the absence of hexose, and suspension in glycerol-containing
      medium resulted in rapid depletion of internal carbohydrate reserves. L. major
      Deltafbp promastigotes were internalized by macrophages and differentiated into
      amastigotes but were unable to replicate in the macrophage phagolysosome.
      Similarly, the mutant persisted in mice but failed to generate normal lesions.
      The data suggest that Leishmania amastigotes reside in a glucose-poor phagosome
      and depend heavily on nonglucose carbon sources. Feeding experiments with
      [(13)C]fatty acids showed that fatty acids are poor gluconeogenic substrates,
      indicating that amino acids are the major carbon source in vivo. The need for
      amino acids may have forced Leishmania spp. to adapt to life in the mature
      phagolysosome.

PMID- 16569702
TI  - The zebrafish homologue of mammalian chimerin Rac-GAPs is implicated in epiboly
      progression during development.
AB  - In this paper, we report an in vivo model for the chimerins, a family of Rac
      GTPase-activating proteins (Rac-GAPs) that are uniquely regulated by the lipid
      second messenger diacylglycerol and have been implicated in the control of actin
      dynamics, migration, and proliferation. We cloned the zebrafish homologue of
      mammalian alpha2-chimerin (chn1) and determined that it possesses Rac-GAP
      activity and a C1 domain with phorbol ester/diacylglycerol-binding capability.
      chn1 morpholino knockdown embryos exhibit severe abnormalities, including the
      development of round somites, lack of yolk extension, and a kinked posterior
      notochord. These zebrafish morphants show Rac hyperactivation and progress faster
      through epiboly, leading to tailbud-stage embryos that have a narrow axis and an
      enlarged tailbud with expanded bmp4 and shh expression. Phenotypic rescue was
      achieved by mRNA microinjection of chn1 or an active chimerin Rac-GAP domain into
      the yolk syncytial layer but not by a chn1 mutant deficient in Rac-GAP activity,
      suggesting that the lack of chn1 Rac-GAP activity in the yolk syncytial layer was
      causative of the misbalance in morphogenetic movements. Our results reveal a
      crucial role for chn1 in early development and implicate Rac as a key regulator
      of morphogenetic movements during zebrafish epiboly.

PMID- 16569703
TI  - A simple artificial light-harvesting dyad as a model for excess energy
      dissipation in oxygenic photosynthesis.
AB  - Under excess illumination, plant photosystem II dissipates excess energy through
      the quenching of chlorophyll fluorescence, a process known as nonphotochemical
      quenching. Activation of nonphotochemical quenching has been linked to the
      conversion of a carotenoid with a conjugation length of nine double bonds
      (violaxanthin) into an 11-double-bond carotenoid (zeaxanthin). It has been
      suggested that the increase in the conjugation length turns the carotenoid from a
      nonquencher into a quencher of chlorophyll singlet excited states, but
      unequivocal evidence is lacking. Here, we present a transient absorption
      spectroscopic study on a model system made up of a zinc phthalocyanine (Pc)
      molecule covalently linked to carotenoids with 9, 10, or 11 conjugated carbon
      carbon double bonds. We show that a carotenoid can act as an acceptor of Pc
      excitation energy, thereby shortening its singlet excited-state lifetime. The
      conjugation length of the carotenoid is critical to the quenching process.
      Remarkably, the addition of only one double bond can turn the carotenoid from a
      nonquencher into a very strong quencher. By studying the solvent polarity
      dependence of the quenching using target analysis of the time-resolved data, we
      show that the quenching proceeds through energy transfer from the excited Pc to
      the optically forbidden S(1) state of the carotenoid, coupled to an
      intramolecular charge-transfer state. The mechanism for excess energy dissipation
      in photosystem II is discussed in view of the insights obtained on this simple
      model system.

PMID- 16569704
TI  - A physical model of axonal damage due to oxidative stress.
AB  - Oxidative damage is implicated in the pathogenesis of neurodegenerative
      disorders, including Alzheimer's, Parkinson's, and Huntington's diseases, and in
      normal aging. Here, we model oxidative stress in neurons using photogenerated
      radicals in a simplified membrane-encapsulated microtubule system. Using
      fluorescence and differential interference contrast microscopies, we monitor
      photochemically induced microtubule breakdown on the supported region of membrane
      in encapsulating synthetic liposomes as a function of lipid composition and
      environment. Degradation of vesicle-encapsulated microtubules is caused by attack
      from free radicals formed upon UV excitation of the lipid-soluble fluorescent
      probe, 6-(9-anthroyloxy)stearic acid. Probe concentration was typically limited
      to a regime in which microtubule degradation was slow, and microtubule
      degradation was monitored by changes in the observed protrusion of the membrane
      surface. The kinetics of microtubule degradation are influenced by lipid
      saturation level, fluorescent probe concentration, and the presence of free
      radical scavengers. This system is sufficient to reproduce some degenerative
      morphologies found in vivo.

PMID- 16569705
TI  - Curriculum content and evaluation of resident competency in clinical pathology
      (laboratory medicine): a proposal.
AB  - Ten years have passed since the Graylyn Conference Report on Laboratory
      Medicine/Clinical Pathology training was issued. Over that time period, the
      Accreditation Council for Graduate Medical Education (ACGME) substantially
      revised the requirements for training programs, the American Board of Pathology
      (ABP) amended both the requirements and the time periods needed for
      certification, and the discipline itself, along with the broader discipline of
      pathology, evolved significantly. Recently, a curriculum proposal in anatomic
      pathology was published as a potential template to be used by training programs
      to help meet these new and evolving needs. Toward the same end, the Academy of
      Clinical Laboratory Physicians and Scientists has now developed a template for a
      curriculum in clinical pathology (laboratory medicine), taking into account newly
      designated and revised areas of residency core competency, the alterations in
      training requirements promulgated by the ACGME and ABP, and the rapidly
      developing nature of the discipline itself. The proposed clinical pathology
      curriculum defines goals and objectives for training, provides guidelines for
      instructional methods, and gives examples of how outcomes can be assessed. This
      curriculum is presented as a potentially helpful outline for use by pathology
      residency training programs.

PMID- 16569706
TI  - High accumulation of platinum-DNA adducts in strial marginal cells of the cochlea
      is an early event in cisplatin but not carboplatin ototoxicity.
AB  - Ototoxicity is a typical dose-limiting side effect of cancer chemotherapy with
      cisplatin but much less so with carboplatin. To elucidate the underlying
      molecular pathological mechanisms, we have measured the formation and persistence
      of drug-induced DNA adducts in the nuclei of inner ear cells of guinea pigs after
      short-term exposure to either cisplatin or carboplatin using immunofluorescence
      staining and quantitative image analysis. After application of carboplatin, all
      cells of the cochlea exhibited a similar burden of guanine-guanine intrastrand
      cross-links in DNA. In contrast, we observed a pronounced 3- to 5-fold
      accumulation of this cytotoxic adduct exclusively in the marginal cells of the
      stria vascularis between 8 and 48 h after treatment with cisplatin. In the
      kidney, the other critical target tissue of cisplatin toxicity, a similar high
      preferential formation of cytotoxic DNA adducts was measured in the tubular
      epithelial cells but not in other renal cell types. As for the ear, this
      excessive formation of DNA damage in a particular cell type was seen in animals
      treated with cisplatin but not those treated with carboplatin. Because cisplatin
      ototoxicity is often attributed to oxidative stress mediated by the generation of
      radical oxygen species (ROS), we have measured in parallel the levels of the lead
      DNA oxidation product 8-oxoguanine (8-oxoG) in cochlear cryosections. Compared
      with basal levels in untreated control cochleas, no additional formation of 8
      oxoG was detectable up to 48 h after cisplatin treatment in the DNA of either
      inner-ear cell type. This suggests that the generation of ROS may be a secondary
      event in cisplatin ototoxicity.

PMID- 16569707
TI  - Relaxin family peptide receptors RXFP1 and RXFP2 modulate cAMP signaling by
      distinct mechanisms.
AB  - Two orphan leucine-rich repeat-containing G protein-coupled receptors were
      recently identified as targets for the relaxin family peptides relaxin and
      insulin-like peptide (INSL) 3. Human gene 2 relaxin is the cognate ligand for
      relaxin family peptide receptor (RXFP) 1, whereas INSL3 is the ligand for RXFP2.
      Constitutively active mutants of both receptors when expressed in human embryonic
      kidney (HEK) 293T cells signal through Galphas to increase cAMP. However, recent
      studies using cells that endogenously express the receptors revealed greater
      complexity: cAMP accumulation after activation of RXFP1 involves a time-dependent
      biphasic pathway with a delayed phase involving phosphoinositide 3-kinase (PI3K)
      and protein kinase C (PKC) zeta, whereas the RXFP2 response involves inhibition
      of adenylate cyclase via pertussis toxin-sensitive G proteins. The aim of this
      study was to compare and contrast the cAMP signaling pathways used by these two
      related receptors. In HEK293T cells stably transfected with RXFP1, preliminary
      studies confirmed the biphasic cAMP response, with an initial Galphas component
      and a delayed response involving PI3K and PKCzeta. This delayed pathway was
      dependent upon G-betagamma subunits derived from Galphai3. An additional
      inhibitory pathway involving GalphaoB affecting cAMP accumulation was also
      identified. In HEK293T cells stably transfected with RXFP2, the cAMP response
      involved Galphas and was modulated by inhibition mediated by GalphaoB and release
      of inhibitory G-betagamma subunits. Thus, initially both RXFP1 and RXFP2 couple
      to Galphas and an inhibitory GalphaoB pathway. Differences in cAMP accumulation
      stem from the ability of RXFP1 to recruit coupling to Galphai3, release G
      betagamma subunits and thus activate a delayed PI3K-PKCzeta pathway to further
      increase cAMP accumulation.

PMID- 16569708
TI  - The phenotypic differentiation of locus ceruleus noradrenergic neurons mediated
      by brain-derived neurotrophic factor is enhanced by corticotropin releasing
      factor through the activation of a cAMP-dependent signaling pathway.
AB  - We have developed a model system of locus ceruleus (LC) neurons in culture, in
      which brain-derived neurotrophic factor (BDNF) induces the emergence of
      noradrenergic neurons attested by the presence of tyrosine hydroxylase (TH) and
      dopamine-beta-hydroxylase and the absence of phenylethanolamine N-methyl
      transferase. Although inactive in itself, the neuropeptide corticotropin
      releasing factor (CRF) strongly amplified the effect of BDNF, increasing the
      number of cells expressing TH and the active accumulation of noradrenaline by a
      factor of 2 to 3 via a mechanism that was nonmitogenic. CRF also acted
      cooperatively with neurotrophin-4, which like BDNF is a selective ligand of the
      TrkB tyrosine kinase receptor. The effect of CRF but not that of BDNF was
      prevented by astressin, a nonselective CRF-1/CRF-2 receptor antagonist. However,
      only CRF-1 receptor transcripts were detectable in LC cultures, suggesting that
      this receptor subtype mediated the effect of CRF. Consistent with the positive
      coupling of CRF-1 receptors to adenylate cyclase, the trophic action of CRF was
      mimicked by cAMP elevating agents. Epac, a guanine nucleotide exchange factor
      directly activated by cAMP, contributed to the effect of CRF through the
      stimulation of extracellular signal-regulated kinases (ERKs) 1/2. However,
      downstream of ERK1/2 activation by CRF, the phenotypic induction of noradrenergic
      neurons relied upon the stimulation of the phosphatidylinositol-3-kinase/Akt
      transduction pathway by BDNF. Together, our results suggest that CRF participates
      to the phenotypic differentiation of LC noradrenergic neurons during development.
      Whether similar mechanisms account for the high degree of plasticity of these
      neurons in the adult brain remains to be established.

PMID- 16569709
TI  - Serum amyloid A induces contrary immune responses via formyl peptide receptor
      like 1 in human monocytes.
AB  - Although the level of serum amyloid A has been reported to be up-regulated during
      inflammatory response, the role of serum amyloid A on the regulation of
      inflammation and immune response has not been elucidated. We found that serum
      amyloid A stimulated the production of tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-10, which are proinflammatory and anti-inflammatory cytokines,
      respectively, in human monocytes. Low concentrations of serum amyloid A
      stimulated TNF-alpha production with maximal activity at 6 h after stimulation,
      whereas high concentrations of serum amyloid A stimulated IL-10 production with
      maximal activity at 12 h. The activations of the two cytokines by serum amyloid A
      occurred at both the transcription and translational levels. Signaling events
      induced by serum amyloid A included the activation of two mitogen-activated
      protein kinases (extracellular signal-regulated kinase and p38 kinase), which
      were found to be required for TNF-alpha and IL-10 production, respectively. The
      stimulation of formyl peptide receptor-like-1-expressing RBL-2H3 cells, but not
      of vector-expressing RBL-2H3 cells with serum amyloid A, induced mitogen
      activated protein kinases activation and the accumulation of the RNAs of these
      two cytokines. Together, our findings suggest that serum amyloid A modulates
      contrary immune responses via formyl peptide receptor-like 1, by inducing TNF
      alpha or IL-10, and demonstrate that extracellular signal-regulated kinase and
      p38 kinase play counteracting roles in this process.

PMID- 16569710
TI  - Untranslated region-dependent exclusive expression of high-sensitivity subforms
      of alpha4beta2 and alpha3beta2 nicotinic acetylcholine receptors.
AB  - alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are recognized as the
      principal nicotine binding site in brain. Recombinant alpha4beta2 nAChR
      demonstrate biphasic concentration-response relationships with low- and high-EC50
      components. This study shows that untranslated regions (UTR) can influence
      expression of high-sensitivity subforms of alpha4beta2 and alpha3beta2 nAChR.
      Oocytes injected with alpha4 and beta2 RNA lacking UTR expressed biphasic
      concentration-response relationships for acetylcholine with high-sensitivity EC50
      values of 0.5 to 2.5 microM (14-24% of the population) and low-sensitivity EC50
      values of 110 to 180 microM (76-86%). In contrast, message with UTR expressed
      exclusively the high-sensitivity alpha4beta2 nAChR subform with an acetylcholine
      EC50 value of 2.2 microM. Additional studies revealed pharmacological differences
      between high- and low-sensitivity alpha4beta2 subforms. Whereas the antagonists
      dihydro-beta-erythroidine (IC50 of 3-6 nM) and methyllycaconitine (IC50 of 40-135
      nM) were not selective between high- and low-sensitivity alpha4beta2,
      chlorisondamine, mecamylamine, and d-tubocurarine were, respectively, 100-, 8-,
      and 5-fold selective for the alpha4beta2 subform with low sensitivity to
      acetylcholine. Conversely, agonists that selectively activated the high
      sensitivity alpha4beta2 subform with respect to efficacy as well as potency were
      identified. Furthermore, two of these agonists were shown to activate mouse brain
      alpha4beta2 as well as the ferret high-sensitivity alpha4beta2 expressed in
      Xenopus laevis oocytes. With the use of UTR-containing RNA, exclusive expression
      of a novel high-sensitivity alpha3beta2 nAChR was also achieved. These studies 1)
      provide further evidence for the existence of multiple subforms of alpha4beta2
      nAChR, 2) extend that to alpha3beta2 nAChR, 3) demonstrate UTR influence on beta2
      containing nAChR properties, and 4) reveal compounds that interact with
      alpha4beta2 in a subform-selective manner.

PMID- 16569711
TI  - Threads and yarns: weaving the tapestry of comorbidity.

PMID- 16569712
TI  - Randomized controlled trials: do they have external validity for patients with
      multiple comorbidities?
AB  - PURPOSE: Many randomized controlled trials (RCTs) exclude patients who have
      multiple comorbidities. The aim of this study was to illustrate the prevalence of
      comorbidities among patients followed up in primary care who would have met the
      inclusion criteria of selected RCTs focusing on treatment of a particular
      condition. We used hypertension as an example of a particular chronic condition.
      METHODS: We used an existing database of 980 patients (660 women) that was
      representative of a population consulting primary care family doctors and that
      contained information about all chronic conditions. We randomly selected 5 RCTs
      that focused on patients with hypertension. The inclusion and exclusion criteria
      used in each of the 5 RCTs were applied (1 study at a time) to the patients in
      our database. The patients from our data set who met the inclusion criteria of a
      given RCT were considered eligible for that RCT. RESULTS: Of the patients from
      our data set who were eligible for each of the RCTs, 89% to 100% had multiple
      chronic conditions. The mean number of chronic conditions of patients eligible
      for each RCT ranged from 5.5 +/- 3.3 to 11.7 +/- 5.3. CONCLUSIONS: Results from
      this study suggest that RCTs targeting a chronic medical condition such as
      hypertension could find that, in a sample taken from family practice, most
      eligible patients have comorbid conditions. Whether these patients are sampled or
      excluded should be reported. Research results intended to be applied in medical
      practice should take the complex reality of effective treatment of these patients
      into consideration.

PMID- 16569713
TI  - Transforming medical care: case study of an exemplary, small medical group.
AB  - PURPOSE: Most published descriptions of organizations providing or improving
      quality of care concern large medical groups or systems; however, 90% of the
      medical care in the United States is provided by groups of no more than 20
      physicians. We studied one such group to determine the organizational and
      cultural attributes that seem related to its achievements in care quality.
      METHODS: A 15-family physician medical group was identified from comparative
      public performance scores of 27 medical groups providing most of the primary care
      in our metropolitan area. Semistructured interviews were conducted with diverse
      personnel in this group, operations were observed, and written documents were
      reviewed. Four primary care physician researchers and a consultant then reviewed
      transcriptions, field notes, and materials during semistructured sessions to
      identify the main attributes of this group and their probable origins. RESULTS:
      This medical group ranked first in a composite measure of preventive services and
      fourth and sixth, respectively, in composite scores for coronary artery disease
      and diabetes care. Our analysis identified 12 attributes of this group that
      seemed to be associated with its good care quality, with patient-centeredness
      being the foundational attribute for most of the others. Historical factors
      important to most of these attributes included small size, physician ownership,
      and a high value on practice consistency among the clinicians in the group.
      CONCLUSIONS: The identified 12 attributes of this medical group seem to be
      associated with its superior care quality, and most of them might be replicable
      by other small groups if they choose to work toward that end.

PMID- 16569714
TI  - Effect of primary health care orientation on chronic care management.
AB  - PURPOSE: It has been suggested that the best way to improve chronic illness care
      is through a redesign of primary care emphasizing comprehensive, coordinated care
      as espoused by the Chronic Care Model (CCM). This study examined the relationship
      between primary care orientation and the implementation of the CCM in physician
      organizations. METHODS: The relationship between measures of primary care
      orientation and the CCM was examined in a sample of 957 physician organizations
      from the National Study of Physician Organizations, a cross-sectional telephone
      survey of all US medical groups and independent practice associations with 20 or
      more physicians (response rate, 70%). RESULTS: After adjusting for potential
      confounders, 6 of 8 measures of primary care orientation were associated with
      physician organizations' adoption of 11 elements of CCM chronic care management.
      These 6 measures were severity of chronic illness treated in primary care, health
      promotion activity, health education activity, any accepted financial risk for
      hospitalization, required reporting, and presence of an electronic standardized
      problem list. Presence of an electronic medical record and the 5-year primary
      care physician turnover rate were not associated. CONCLUSIONS: Organizations that
      have adopted 6 core attributes of primary care, representing comprehensive health
      service delivery and a commitment to overall patient health, appear to use more
      chronic care management practices. Policy makers and other stakeholders may wish
      to focus on creating an improved primary care home in their quest to close the
      "quality chasm" in chronic illness care.

PMID- 16569715
TI  - Physicians, patients, and the electronic health record: an ethnographic analysis.
AB  - PURPOSE: Little is known about the effects of the electronic health record (EHR)
      on physician-patient encounters. The objectives of this study were to identify
      the factors that influence the manner by which physicians use the EHR with
      patients. METHODS: This ethnographic study included 4 qualitative components: 80
      hours of participant observation in 4 primary care offices in the Pacific
      Northwest; individual interviews with 52 patients, 12 office staff members, 23
      physicians, and 1 nurse-practitioner; videotaped reviews of 29 clinical
      encounters; and 5 focus-group interviews with physicians and computer advocates.
      The main outcome measures were factors that influence how physicians use the EHR.
      Researchers qualitatively derived these factors through serial reviews of data.
      RESULTS: This study identified 14 factors that influence how EHRs are used and
      perceived in medical practice today. These factors were categorized into 4
      thematic domains: (1) spatial--effect of the physical presence and location of
      EHRs on interactions between physicians and patients; (2) relational--perceptions
      of physicians and patients about the EHR and how those perceptions affected its
      use; (3) educational--issues of developing physicians' proficiency with and
      improving patients' understandings about EHR use; and (4) structural-
      institutional and technological forces that influence how physicians perceived
      their use of EHR. CONCLUSIONS: This study found that the introduction of EHRs
      into practice influences multiple cognitive and social dimensions of the clinical
      encounter. It brings into focus important questions that through further inquiry
      can determine how to make best use of the EHR to enhance therapeutic
      relationships.

PMID- 16569716
TI  - Nasal carriage of Staphylococcus aureus and methicillin-resistant S aureus in the
      United States, 2001-2002.
AB  - PURPOSE: Staphylococcus aureus is a common cause of invasive infections, yet most
      assessments of prevalence are based on health care-based samples. We computed
      population-based estimates of nasal carriage of S aureus and risk factors for
      carriage, as well as population-based estimates of nasal carriage of methicillin
      resistant S aureus (MRSA). METHODS: We used the National Health and Nutrition
      Examination Survey (NHANES) 2001-2002 to estimate carriage of S aureus and MRSA
      for the non-institutionalized US population including children and adults.
      RESULTS: An estimated 86.9 million persons (32.40% of the population) were
      colonized with S aureus. The prevalence of MRSA among S aureus isolates was
      2.58%, for an estimated population carriage of MRSA of 0.84% or 2.2 million
      persons. Among individuals with S aureus isolates, individuals aged 65 years or
      older had the highest MRSA prevalence (8.28%). Among all the racial/ethnic groups
      studied, Hispanics had the highest prevalence of colonization with S aureus but,
      when colonized, were less likely to have MRSA. CONCLUSIONS: This first nationally
      representative assessment of carriage of S aureus indicates that nearly one third
      of the population is currently colonized by this organism. Although the
      prevalence of MRSA remains low, more than 2.2 million people carry this resistant
      organism; thus, vigilance in promoting appropriate microbial transmission
      protocols should remain a priority.

PMID- 16569717
TI  - Services provided by family physicians for patients with occupational injuries
      and illnesses.
AB  - PURPOSE: Many family doctors provide care to patients with occupational injuries
      and illnesses, but little is known about the type of medical services provided,
      or how they compare with services provided by other types of physicians. This
      study used national data to develop a statistical profile of office-based medical
      care delivered by family physicians to patients with work-related disorders.
      METHODS: Using data from 4 years (1997-2000) of the National Ambulatory Medical
      Care Survey, we classified visits for patients with work-related conditions
      according to patient and physician characteristics, services provided, and other
      visit characteristics. For comparison, we also compiled profiles for visits to
      other types of physicians for treatment of work-related disorders, and for visits
      to family physicians for treatment of nonoccupational conditions. RESULTS:
      Analyses were based on 96,183 office visits made to 4,947 physicians. A majority
      of visits made to family physicians for occupational conditions involved patients
      seeing their regular primary care doctor. Possibly for this reason, patients at
      these visits were more likely to have their blood pressure taken, receive
      diagnostic and screening services, and have prescription drugs prescribed or
      administered, compared with patients seeing other types of physicians. Only 73.3%
      of visits to family physicians for work-related disorders were expected to be
      paid for by workers' compensation insurance. CONCLUSIONS: Our findings suggest
      that the distinctive types of care provided by family physicians to injured
      workers may be related to their role as the patients' regular physician. This
      finding is relevant to the proposals being considered by many states to expand
      employers' and insurers' ability to choose the treating physician in workers'
      compensation cases.

PMID- 16569718
TI  - A practice-sponsored Web site to help patients pursue healthy behaviors: an ACORN
      study.
AB  - PURPOSE: We tested whether patients are more likely to pursue healthy behaviors
      (eg, physical activity, smoking cessation) if referred to a tailored Web site
      that provides valuable information for behavior change. METHODS: In a 9-month pre
      post comparison with nonrandomized control practices, 6 family practices (4
      intervention, 2 control) encouraged adults with unhealthy behaviors to visit the
      Web site. For patients from intervention practices, the Web site offered tailored
      health advice, a library of national and local resources, and printouts for
      clinicians. For patients from control practices, the Web site offered static
      information pages. Patient surveys assessed stage of change and health behaviors
      at baseline and follow-up (at 1 and 4 months), Web site use, and satisfaction.
      RESULTS: During the 9 months, 932 patients (4% of adults attending the practice)
      visited the Web site, and 273 completed the questionnaires. More than 50% wanted
      physician assistance with health behaviors. Stage of change advanced and health
      behaviors improved in both intervention and control groups. Intervention patients
      reported greater net improvements at 1 month, although the differences approached
      significance only for physical activity and readiness to change dietary fat
      intake. Patients expressed satisfaction with the Web site but wished it provided
      more detailed information and greater interactivity with clinicians. CONCLUSIONS:
      Clinicians face growing pressure to offer patients good information on health
      promotion and other health care topics. Referring patients to a well-designed Web
      site that offers access to the world's best information is an appealing
      alternative to offering handouts or impromptu advice. Interactive Web sites can
      facilitate behavior change and can interface with electronic health records.
      Determining whether referral to an informative Web site improves health outcomes
      is a methodological challenge, but the larger question is whether information
      alone is sufficient to promote behavior change. Web sites are more likely to be
      effective as part of a suite of tools that incorporate personal assistance.

PMID- 16569719
TI  - Triage and diagnosis of chest pain in rural hospitals: implementation of the ACI
      TIPI in the High Plains Research Network.
AB  - PURPOSE: The Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI
      TIPI) has been shown to improve diagnostic accuracy of acute cardiac ischemia
      (ACI) and decrease coronary care unit admissions in urban emergency departments.
      The purpose of this study was to determine the impact of the ACI-TIPI on triage
      and diagnosis of patients with chest pain in rural hospitals. METHODS: We
      undertook a controlled trial of the impact ACI-TIPI use in the High Plains
      Research Network (HPRN). Main outcome measures were the triage of patients in
      emergency departments (admission, transfer, or discharge home) and diagnostic
      accuracy. RESULTS: There were 1,861 patients seen during a 10-month period. Forty
      five percent of all patients complaining of chest pain were discharged home from
      the emergency department. Eight percent were transferred from the emergency
      department, and another 10% were transferred later after admission. Among
      patients with acute myocardial infarction or unstable angina, 22.2% were
      transferred directly from the emergency department and only 3% were discharged
      home when ACI-TIPI was available, compared with 18.7% transferred and 5.2%
      discharged home when not available (P = .4). Diagnostic accuracy was high and not
      statistically different with the addition of the ACI-TIPI score (86.8% ACI-TIPI
      off vs 89.0% ACI-TIPI on, P = .15), CONCLUSIONS: Physicians in the HPRN provided
      appropriate diagnosis and triage to patients with chest pain. Routine addition of
      the ACI-TIPI score did not improve diagnostic accuracy or significantly change
      triage. Further research on ACI-TIPI in rural hospitals is necessary before
      recommending routine use of the ACI-TIPI.

PMID- 16569720
TI  - Postpartum health of employed mothers 5 weeks after childbirth.
AB  - PURPOSE: Most new mothers return to work soon after childbirth. A need exists to
      reexamine the definition of postpartum health and evaluate employed women's
      recovery from childbirth in association with such factors as delivery type and
      breastfeeding. METHODS: Using a prospective cohort design, we recruited Minnesota
      women into the study while they were hospitalized for childbirth in 2001.
      Telephone interviews were conducted 5 weeks postpartum. Eligible women were 18
      years or older, employed, and spoke English. Multivariate models using 2-stage
      least squares were used to estimate factors associated with physical and mental
      health and postpartum symptoms. RESULTS: A total of 817 women were enrolled (71%
      response) in the study; 716 women completed interviews at 5 weeks postpartum. On
      average, women reported 6 postpartum symptoms, most frequently fatigue (64%),
      breast discomfort (60%), and decreased desire for sex (52%). Findings showed that
      cesarean (vs vaginal) deliveries were associated with significantly worse
      physical function, role limitations, and vitality. Multivariate findings showed
      that the effect of delivery type on physical health was moderately large (beta = 
      5.96; P = or <.01), and breastfeeding was associated with an increased frequency
      of postpartum symptoms (beta = 4.63; P = .01). CONCLUSIONS: These mothers
      experienced several childbirth-related symptoms at 5 weeks postpartum, indicating
      a need for ongoing rest and recovery. Health concerns were greater for women who
      were breastfeeding and for those whose babies were delivered by cesarean section,
      suggesting a need for greater support for these women and a reassessment by the
      medical community of the progressively growing practice of cesarean deliveries.

PMID- 16569721
TI  - Helping 'them': our role in recovery from opioid dependence.
AB  - The crisis of opioid addiction in America has been fueled by the diversion of
      prescription pain pills and the emergence of pure and inexpensive heroin. Until
      recently, benefits of and access to therapy were limited. This situation changed
      in 2003 with Food and Drug Administration approval of buprenorphine for the
      office-based treatment of opioid dependence. Now armed with a potent drug,
      primary care physicians can treat addicted patients in their own practice and
      from their own neighborhood, but first we must overcome deficiencies in our
      training and personal biases about addicts and what they need. This a report of
      one doctor's progress.

PMID- 16569723
TI  - Graham Center article and Katrina forum.

PMID- 16569722
TI  - Facilitating collaboration among academic generalist disciplines: a call to
      action.
AB  - To meet its population's health needs, the United States must have a coherent
      system to train and support primary care physicians. This goal can be achieved
      only though genuine collaboration between academic generalist disciplines.
      Academic general pediatrics, general internal medicine, and family medicine may
      be hampering this effort and their own futures by lack of collaboration. This
      essay addresses the necessity of collaboration among generalist physicians in
      research, medical education, clinical care, and advocacy. Academic generalists
      should collaborate by (1) making a clear decision to collaborate, (2) proactively
      discussing the flow of money, (3) rewarding collaboration, (4) initiating regular
      generalist meetings, (5) refusing to tolerate denigration of other generalist
      disciplines, (6) facilitating strategic planning for collaboration among
      generalist disciplines, and (7) learning from previous collaborative successes
      and failures. Collaboration among academic generalists will enhance opportunities
      for trainees, primary care research, and advocacy; conserve resources; and
      improve patient care.

PMID- 16569724
TI  - Aligning the interests of osteopathic and allopathic teachers of family medicine.

PMID- 16569725
TI  - Keeping our eye on the ball: managing the evolution of Electronic Health Records.

PMID- 16569726
TI  - Commentary: pre-morbid IQ and later health--the rapidly evolving field of
      cognitive epidemiology.

PMID- 16569727
TI  - Application of physiologically based pharmacokinetic modeling in setting acute
      exposure guideline levels for methylene chloride.
AB  - Acute exposure guideline levels (AEGLs) are derived to protect the human
      population from adverse health effects in case of single exposure due to an
      accidental release of chemicals into the atmosphere. AEGLs are set at three
      different levels of increasing toxicity for exposure durations ranging from 10
      min to 8 h. In the AEGL setting for methylene chloride, specific additional
      topics had to be addressed. This included a change of relevant toxicity endpoint
      within the 10-min to 8-h exposure time range from central nervous system
      depression caused by the parent compound to formation of carboxyhemoglobin (COHb)
      via biotransformation to carbon monoxide. Additionally, the biotransformation of
      methylene chloride includes both a saturable step as well as genetic polymorphism
      of the glutathione transferase involved. Physiologically based pharmacokinetic
      modeling was considered to be the appropriate tool to address all these topics in
      an adequate way. Two available PBPK models were combined and extended with
      additional algorithms for the estimation of the maximum COHb levels. The model
      was validated and verified with data obtained from volunteer studies. It was
      concluded that all the mentioned topics could be adequately accounted for by the
      PBPK model. The AEGL values as calculated with the model were substantiated by
      experimental data with volunteers and are concluded to be practically applicable.

PMID- 16569728
TI  - Toxicological safety evaluation of DNA plasmid vaccines against HIV-1, Ebola,
      Severe Acute Respiratory Syndrome, or West Nile virus is similar despite
      differing plasmid backbones or gene-inserts.
AB  - The Vaccine Research Center has developed a number of vaccine candidates for
      different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome
      virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant-IL
      2/Ig) based on a DNA plasmid vaccine platform. To support the clinical
      development of each of these vaccine candidates, preclinical studies were
      performed to screen for potential toxicities (intrinsic and immunotoxicities).
      All treatment-related toxicities identified in these repeated-dose toxicology
      studies have been confined primarily to the sites of injection and seem to be the
      result of both the delivery method (as they are seen in both control and treated
      animals) and the intended immune response to the vaccine (as they occur with
      greater frequency and severity in treated animals). Reactogenicity at the site of
      injection is generally seen to be reversible as the frequency and severity
      diminished between doses and between the immediate and recovery termination time
      points. This observation also correlated with the biodistribution data reported
      in the companion article (Sheets et al., 2006), in which DNA plasmid vaccine was
      shown to remain at the site of injection, rather than biodistributing widely, and
      to clear over time. The results of these safety studies have been submitted to
      the Food and Drug Administration to support the safety of initiating clinical
      studies with these and related DNA plasmid vaccines. Thus far, standard repeated
      dose toxicology studies have not identified any target organs for toxicity (other
      than the injection site) for our DNA plasmid vaccines at doses up to 8 mg per
      immunization, regardless of disease indication (i.e., expressed gene-insert) and
      despite differences (strengths) in the promoters used to drive this expression.
      As clinical data accumulate with these products, it will be possible to
      retrospectively compare the safety profiles of the products in the clinic to the
      results of the repeated-dose toxicology studies, in order to determine the
      utility of such toxicology studies for signaling potential immunotoxicities or
      intrinsic toxicities from DNA vaccines. These data build on the biodistribution
      studies performed (see companion article, Sheets et al., 2006) to demonstrate the
      safety and suitability for investigational human use of DNA plasmid vaccine
      candidates for a variety of infectious disease prevention indications.

PMID- 16569730
TI  - Altered methylation in gene-specific and GC-rich regions of DNA is progressive
      and nonrandom during promotion of skin tumorigenesis.
AB  - Altered DNA methylation, an epigenetic mechanism, likely contributes to
      tumorigenesis, with an inverse relationship existing between methylation in a
      promoter region and transcription. Using the SENCAR two-stage mouse skin
      tumorigenesis model, altered methylation was characterized in precancerous tissue
      and in tumor tissue. Mouse skin was initiated with 7,12-dimethylbenz[a]anthracene
      and promoted three times a week with 3, 9, 18, or 27 mg cigarette smoke
      condensate (CSC) for 4, 8, or 29 weeks; tumors were collected at 29 weeks. In
      addition, reversibility of changes in methylation was assessed following
      cessation of the promoting stimulus. DNA was isolated, and GC-rich methylation
      was assessed quantitatively via methylation-sensitive restriction digestion,
      arbitrarily primed PCR, and electrophoretic separation of PCR products. Analysis
      focused on regions of altered methylation (RAMs), which persisted from 4 to 8
      weeks and from 8 weeks to tumor tissue. Persistent RAMs (i.e., seen in
      precancerous tissue and carried forward to tumors) are likely to play a key role
      in tumorigenesis. Twenty-two CpG sites in the upstream region of the Ha-ras
      promoter were unmethylated in control skin, 27 mg CSC, and tumor tissue. At two
      CpG sites closer to the transcriptional start site the incidence of
      hypomethylation increased with the dose of CSC. Hypomethylation was detected in
      all tumor samples. Expression of Ha-ras increased with 18 and 27 mg CSC promotion
      and more so in tumor tissue. These data support our hypothesis that tumor
      promotion involves instability of the epigenome, providing an environment where
      changes in the methylation status of specific regions of the genome accumulate
      progressively and contribute to the clonal expansion of initiated cells that
      leads to tumor formation.

PMID- 16569729
TI  - Biodistribution of DNA plasmid vaccines against HIV-1, Ebola, Severe Acute
      Respiratory Syndrome, or West Nile virus is similar, without integration, despite
      differing plasmid backbones or gene inserts.
AB  - The Vaccine Research Center has developed a number of vaccine candidates for
      different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome
      virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant-IL
      2/Ig) based on a DNA plasmid vaccine platform. To support the clinical
      development of each of these vaccine candidates, preclinical studies have been
      performed in mice or rabbits to determine where in the body these plasmid
      vaccines would biodistribute and how rapidly they would clear. In the course of
      these studies, it has been observed that regardless of the gene insert
      (expressing the vaccine immunogen or cytokine adjuvant) and regardless of the
      promoter used to drive expression of the gene insert in the plasmid backbone, the
      plasmid vaccines do not biodistribute widely and remain essentially in the site
      of injection, in the muscle and overlying subcutis. Even though approximately
      10(14) molecules are inoculated in the studies in rabbits, by day 8 or 9 (
      approximately 1 week postinoculation), already all but on the order of 10(4)
      10(6) molecules per microgram of DNA extracted from tissue have been cleared at
      the injection site. Over the course of 2 months, the plasmid clears from the site
      of injection with only a small percentage of animals (generally 10-20%) retaining
      a small number of copies (generally around 100 copies) in the muscle at the
      injection site. This pattern of biodistribution (confined to the injection site)
      and clearance (within 2 months) is consistent regardless of differences in the
      promoter in the plasmid backbone or differences in the gene insert being
      expressed by the plasmid vaccine. In addition, integration has not been observed
      with plasmid vaccine candidates inoculated i.m. by Biojector 2000 or by needle
      and syringe. These data build on the repeated-dose toxicology studies performed
      (see companion article, Sheets et al., 2006) to demonstrate the safety and
      suitability for investigational human use of DNA plasmid vaccine candidates for a
      variety of infectious disease prevention indications.

PMID- 16569731
TI  - Radiation exposure impairs luteinizing hormone signal transduction and
      steroidogenesis in cultured human leydig cells.
AB  - Therapeutic, accidental, and experimental radiation exposures decreased serum
      testosterone in males, leading to various sexual problems. Since testicular
      Leydig cells are the predominant source of circulating testosterone, findings on
      the direct effects of radiation on Leydig cell steroidogenesis and the mechanism
      behind such effects would be of greater importance to the use of safer radiation
      doses in cancer therapy and to adopt preventive or therapeutic measures to
      alleviate postirradiation lesions, respectively. Therefore, this study was
      undertaken to explore the same using cultured human Leydig cells. Testicles
      removed from advanced prostatic carcinoma patients were used for isolation and
      purification of Leydig cells. Purified Leydig cells were cultured and then
      exposed to different doses (2, 4, 6, 8, and 10 Gy) of fractioned gamma radiation.
      Normal and irradiated cells were used for luteinizing hormone (LH) receptor
      quantification or total RNA isolation to study LH receptor mRNA expression or
      LH/cyclic AMP (cAMP) stimulation test. While LH-stimulated cells were used for
      cAMP assay, LH- and cAMP-stimulated cells were used for the estimation of
      steroidogenic enzymes, testosterone and estradiol production. Radiation exposure
      caused adverse effects on Leydig cell steroidogenesis in a dose-dependent manner.
      While lower doses (2 and 4 Gy) were ineffective, higher doses (6 Gy and above)
      drastically decreased LH receptor, basal and LH-stimulated cAMP generation, and
      basal, LH-, and cAMP-stimulated steroidogenesis. While 2 Gy of radiation exposure
      increased the LH receptor mRNA level, other doses did not induce any significant
      change. Therefore, it is concluded that higher doses of radiation impair Leydig
      cell steroidogenesis by affecting LH signal transduction at the level of both pre
      and post-cAMP generation. Decreased level of LH receptors following higher doses
      of radiation exposure is not coupled with impaired expression of its mRNA.

PMID- 16569732
TI  - Aldosterone blockade attenuates urinary monocyte chemoattractant protein-1 and
      oxidative stress in patients with type 2 diabetes complicated by diabetic
      nephropathy.
AB  - CONTEXT: Aldosterone causes organic impairment by enhancement of oxidative stress
      and subsequent induction of proinflammatory cytokines and chemokines. OBJECTIVE:
      This study was designed to investigate the effect of spironolactone, an
      aldosterone blocker, on oxidative stress and the level of urinary monocyte
      chemoattractant protein (MCP)-1, a cysteine-cysteine chemokine that may
      contribute to progression of various nephropathies in type 2 diabetic patients
      with diabetic nephropathy. DESIGN, SETTING, PATIENTS AND OTHER PARTICIPANTS, AND
      INTERVENTION: The patients were randomly assigned to two groups in which they
      received either spironolactone (50 mg/d; n = 23) or amlodipine (2.5 mg/d; n =
      14). MAIN OUTCOME MEASURES: Urinary 8-iso-prostaglandin (PG) F2alpha (a marker of
      oxidative stress), urinary MCP-1, and urinary albumin excretion (UAE) were
      measured at the start of administration (0 months) and after 3 months in each
      group. Baseline levels of these variables were also measured in 25 age-matched
      healthy subjects. RESULTS: There were significant positive correlations between
      log(10)-transformed (log) 8-iso-PGF2alpha and log MCP-1 levels in control and
      diabetic subjects and all subjects combined, but no correlations between log UAE
      and log 8-iso-PGF2alpha or log MCP-1 were found in any group. Significant
      decreases in 8-iso-PGF2alpha, MCP-1, and UAE were observed with spironolactone (P
      = 0.0001, P = 0.0041, and P = 0.0037, respectively), and systolic blood pressure
      significantly decreased after both spironolactone and amlodipine therapy (P =
      0.00011 and P = 0.0051, respectively). CONCLUSIONS: Our data suggest that urinary
      MCP-1 is correlated with oxidative stress as measured by urinary 8-iso-PGF2alpha
      and that spironolactone can decrease urinary MCP-1 and oxidative stress.

PMID- 16569733
TI  - Serum C-reactive protein and its relation to cardiovascular risk factors and
      adipocytokines in Japanese children.
AB  - BACKGROUND: C-Reactive protein (CRP) is an independent risk factor for
      atherosclerotic coronary heart diseases (ACHD) in adults. To help prevent ACHD,
      it may be useful to understand risk factors during childhood. OBJECTIVE: The
      objective of this study was to investigate serum CRP and its relation to other
      risk factors for ACHD and adipocytokines (adiponectin, IL-6, and TNF-alpha) in
      Japanese children. METHODS: CRP, conventional risk factors for ACHD, and
      adipocytokines were determined in 568 children (340 boys and 228 girls, aged 7-10
      yr). Serum concentrations of adipocytokines were measured by sandwich ELISA.
      RESULTS: Children with high CRP concentrations (highest tertile) had higher body
      mass index (BMI) sd scores, insulin, insulin resistance, uric acid, and
      adipocytokines and had more atherogenic lipoprotein profiles than other children.
      However, after being corrected by BMI sd, only high-density lipoprotein
      cholesterol, apolipoprotein A-I, IL-6, and TNF-alpha for boys and high-density
      lipoprotein cholesterol, apolipoprotein B, uric acid, IL-6, and TNF-alpha for
      girls were significantly correlated with CRP. IL-6 was the strongest predictive
      variable for CRP and accounted for 26.2 and 27.7% of the variability in serum
      concentrations of CRP in boys and girls, respectively. Serum concentrations of IL
      6 were partly dependent on BMI sd and TNF-alpha in both boys and girls.
      CONCLUSION: Although serum concentrations of CRP are partly regulated by
      adipocytokines and conventional risk factors for ACHD, high CRP levels were
      associated with atherogenic profiles of cardiovascular risk factors in children.
      Our findings suggest that it may be important to control body weight to prevent
      an increase in serum CRP in children.

PMID- 16569734
TI  - Relation between circulating angiotensin II type 1 receptor agonistic
      autoantibodies and soluble fms-like tyrosine kinase 1 in the pathogenesis of
      preeclampsia.
AB  - CONTEXT: Placental and circulatory soluble fms-like tyrosine kinase 1 (sFlt1) has
      proven to be elevated in pregnant women with preeclampsia, a disease
      characterized by hypertension, proteinuria, and endothelial dysfunction. Recent
      studies also demonstrated an autoantibody against the angiotensin II type 1 (AT1)
      receptor (AT1-AA) in that disease. OBJECTIVE: Both factors are discussed as key
      players in the etiology of preeclampsia. However, it has not yet been clarified
      whether these two circulating factors correlate and whether synergy determines
      the severity of pathology. DESIGN: AT1-AA was retrospectively determined by a
      bioassay and sFlt1 by an ELISA. PATIENTS: Serum from second-trimester pregnancies
      with normal or abnormal uterine perfusion and in women at term with or without
      pregnancy pathology was analyzed. RESULTS: Most of the preeclamptic patients were
      characterized by high sFlt1 levels and the presence of AT1-AA, although the
      agonistic effects of the antibody did not correlate with the sFlt1 concentrations
      (P = 0.85). Although AT1-AA was also detected in second-trimester pregnancies
      evidencing abnormal uterine perfusion without later pathology, sFlt1 was not
      significantly elevated in these pregnancies, compared with those with normal
      uterine perfusion. However, whereas women with abnormal perfusion and later
      pregnancy pathology did not differ in AT1-AA, compared with those with normal
      outcome, sFlt1 was significantly increased. Again, the two factors did not
      correlate (P = 0.15). CONCLUSIONS: We conclude that AT1-AA bioactivity and sFlt1
      concentrations do not correlate, are not mutually dependent, and are thus
      probably involved in distinct pathogenetic mechanisms. Both factors in
      combination may not be causative for the early impaired trophoblast invasion and
      pathological uterine perfusion.

PMID- 16569735
TI  - Selective activation of somatostatin receptor subtypes differentially modulates
      secretion and viability in human medullary thyroid carcinoma primary cultures:
      potential clinical perspectives.
AB  - CONTEXT: Medullary thyroid carcinoma (MTC) is a rare tumor originating from
      thyroid parafollicular C cells. We previously demonstrated that somatostatin
      (SRIH) reduces cell growth in the human MTC cell line, TT, which expresses all
      SRIH receptor (SSTR) subtypes and responds differently to selective SSTR
      agonists. OBJECTIVE: To clarify the possible effects of SRIH analogs on hormone
      secretion and proliferation in MTC primary cultures, we evaluated SSTR expression
      and assessed the in vitro effects on calcitonin (CT) and chromogranin A secretion
      as well as cell viability of SRIH analogs interacting with SSTR1, SSTR2, and
      SSTR5. DESIGN: Thirty-five patients affected by MTC were recruited from 2003 to
      2005. After total thyroidectomy, the samples were examined for CT, chromogranin
      A, and SSTR expression by RT-PCR. Primary cultures were developed and tested with
      SRIH analogs interacting with SSTR1, SSTR2, and SSTR5. RESULTS: We selected 18
      MTC tumor samples, expressing SSTR1, SSTR2, and SSTR5. Two different groups were
      identified according to CT secretion inhibition by the clinically available SRIH
      analog, lanreotide. In the responder group, CT secretion was reduced by compounds
      interacting with SSTR1, SSTR2, and SSTR5, whereas cell viability was not
      affected. On the other hand, in the nonresponder group, CT secretion was reduced
      by the SSTR1 selective agonist, whereas cell viability was inhibited by SSTR2
      selective agonists. CONCLUSIONS: Our data suggest that SRIH analogs might be
      useful in medical therapy of MTC because they could have antiproliferative
      effects despite the lack of antisecretory activity and vice versa.

PMID- 16569736
TI  - PRKAR1A Mutations and protein kinase A interactions with other signaling pathways
      in the adrenal cortex.
AB  - CONTEXT: Primary pigmented nodular adrenocortical disease, associated with Carney
      complex, is caused by mutations in PRKAR1A (mt-PRKAR1A), a gene that codes for
      the regulatory subunit type 1alpha (RIalpha) of cAMP-dependent protein kinase
      (PKA). PRKAR1A inactivation is associated with dysregulated PKA activity that is
      thought to result in tumorigenesis. mt-PRKAR1A-bearing lymphocytes from Carney
      complex patients exhibit enhanced cell proliferation associated with increased
      expression of the MAPK ERK1/2 pathway. OBJECTIVE: The objective of the study was
      to determine how PKA and its subunits and ERK1/2 and their molecular partners
      change in the presence of PRKAR1A mutations in adrenocortical tissue. DESIGN: PKA
      activity and subunit expression, ERK1/2, other immunoassays, and
      immunohistochemistry on adrenocortical samples from patients with germline normal
      or mt-PRKAR1A were analyzed. RESULTS: Increased cAMP-stimulated total kinase
      activity was associated with mt-PRKAR1A. PKA subunit expression analysis in mt
      PRKAR1A tissues, by quantitative mRNA assay and immunoblotting, showed a 2.4-fold
      (P = 0.02) and 1.8-fold (P = 0.09) decrease in RIalpha's message and protein,
      respectively, and increases in other PKA subunits. Immunoassays showed 2-fold (P
      = 0.03) and 6-fold (P = 0.03) decreases in baseline ERK1/2, with corresponding
      increases in phosphorylated (p) ERK1/2 in mt-PRKAR1A samples. B-raf kinase, p
      MEK1/2, and p-c-Myc, but not p-Akt/protein kinase B, were significantly
      increased. Immunohistochemistry studies supported these data. CONCLUSIONS: mt
      PRKAR1A causes increased total cAMP-stimulated kinase activity, likely the result
      of up-regulation of other PKA subunits caused by down-regulation of RIalpha, as
      seen in human lymphocytes and mouse animal models. These changes, associated with
      enhanced MAPK activity, may be, in part, responsible for the proliferative
      signals that result in primary pigmented nodular adrenocortical disease.

PMID- 16569737
TI  - Diagnostic criteria for polycystic ovary syndrome and ovarian morphology in women
      with type 1 diabetes mellitus.
AB  - CONTEXT: The criteria for diagnosis of polycystic ovary syndrome (PCOS) have been
      modified and now include polycystic ovary morphology (PCOM). OBJECTIVE: The
      purpose of this study was to determine the frequency of PCOS and PCOM in women
      with type 1 diabetes mellitus (DM1). DESIGN: We evaluated the clinical, hormonal,
      and ultrasonographic characteristics in women with DM1 and compared them with a
      carefully matched group of normal women in a cross-sectional study. SETTING: The
      study was conducted at an academic research institute located within a general
      hospital. PATIENTS: All the women with DM1 attending our hospital who had
      experienced menarche at least 2.5 yr earlier were invited to participate and were
      compared with healthy women with regular menses and without a history of
      hyperandrogenism [controls (C)]. RESULTS: Hirsutism was present in 28.6 and 0.0%
      of DM1 and C, respectively (P < 0.001). Biochemical hyperandrogenism was present
      in 23.8 and 7.9% of DM1 and C, respectively. DM1 women had higher levels of
      testosterone and androstenedione and larger ovarian volume and follicle number by
      ovary than C. PCOM was present in 54.8% of DM1 and 13.2% of C (P < 0.001).
      Oligomenorrhea was present in 19% of women with DM1. The frequency of PCOS was
      40.5 and 2.6% in DM1 and C, respectively (relative risk, 15.4; 95% confidence
      interval, 2.2-110.2; P < 0.0001). The proportion of women using intensive insulin
      treatment was higher in those with PCOM/PCOS (P < 0.05). Intensive treatment was
      a significant factor over having PCOM/PCOS (P < 0.05). CONCLUSIONS: A high
      frequency of hyperandrogenism, PCOM, and PCOS is observed in DM1, which appears
      to be associated with intensive insulin treatment.

PMID- 16569738
TI  - Allelic variants of the gamma-aminobutyric acid-A receptor alpha1-subunit gene
      (GABRA1) are not associated with idiopathic gonadotropin-dependent precocious
      puberty in girls with and without electroencephalographic abnormalities.
AB  - CONTEXT: gamma-Aminobutyric acid (GABA) is a dominant inhibitory neurotransmitter
      involved in the modulation of brain electric activity and puberty onset in
      primates. GABA inhibitory effects on GnRH neurons are mainly mediated by GABA-A
      receptor alpha1-subunit. OBJECTIVE: The objective of this study was to
      investigate functional mutations or polymorphisms of the GABA-A receptor alpha1
      subunit gene (GABRA1) in girls with idiopathic gonadotropin-dependent precocious
      puberty (GDPP) with and without electroencephalographic (EEG) abnormalities.
      DESIGN: The entire coding region of GABRA1 was sequenced in all patients. Two
      known GABRA1 polymorphisms were investigated by GeneScan software analysis or
      enzymatic restriction. Seventy-three normal women were used as controls for
      genetic study. EEG tracings were recorded in 23 girls with GDPP and 17 girls with
      adequate pubertal development. SETTING: The study was performed at a university
      hospital. PATIENTS: Thirty-one girls from 28 unrelated families with idiopathic
      GDPP were studied. RESULTS: Automatic sequencing revealed no functional mutations
      in girls with GDPP. Seven different GABRA1 polymorphisms, including two exonic
      (156T>C and 1323G>A) and five intronic [IVS2-712(GT)n, IVS3+12A>T, IVS8+45T>G,
      IVS9+76A>G, and IVS10+15G>A], were found in GDPP girls and controls. Abnormal EEG
      tracings were found in 26% of 23 girls with GDPP, two of them with epilepsy. The
      genotype and allele frequencies of the GABRA1 polymorphisms were not
      statistically different between unrelated GDPP girls and controls or between GDPP
      girls with or without EEG abnormalities. CONCLUSIONS: GABRA1 functional mutations
      or polymorphisms are not associated with the intrinsic mechanism of GDPP in girls
      with and without EEG abnormalities.

PMID- 16569739
TI  - A novel point mutation in P450c17 (CYP17) causing combined 17alpha
      hydroxylase/17,20-lyase deficiency.
AB  - CONTEXT: Combined 17alpha-hydroxylase/17,20-lyase deficiency is a rare cause of
      congenital adrenal hyperplasia and hypogonadism. Novel single amino acid changes
      in P450c17 provide potentially important insights into key structural domains for
      enzyme function. OBJECTIVE, DESIGN, AND SETTING: We report a novel missense
      mutation in P450c17 in a 17-yr-old female presenting with a malignant mixed germ
      cell tumor with yolk sac elements who demonstrated clinical and biochemical
      features of combined 17alpha-hydroxylase/17,20-lyase deficiency. METHODS:
      Quantitative urinary steroid analysis was performed by high resolution gas
      chromatography. All eight coding exons of CYP17 were PCR amplified and sequenced.
      The position of arginine at codon 96 was modeled using the CYP17 structure 2c17
      (www.rcsb.org). The CYP17 genes were subcloned into pcDNA3, expressed in HEK-293
      cells, and chromatographed. PATIENT AND RESULTS: 17alpha-Hydroxylase deficiency
      was confirmed by marked reductions in urinary and serum cortisol, androgens, and
      estradiol. Mutational analysis revealed a novel homozygous R96Q missense mutation
      in P450c17, affecting an amino acid in a key substrate-binding region of the
      enzyme, leading to complete inactivity. CONCLUSION: The description of a second
      missense mutation at codon 96 (R96W and R96Q) in the substrate-binding region of
      P450c17 provides strong evidence for the key role of this amino acid in 17alpha
      hydroxylase/17,20-lyase function. An association between a malignant germ cell
      tumor and 17alpha-hydroxylase deficiency has not been reported previously,
      although the presence of gonadoblastoma in the ovary of a patient with this
      condition has recently been described.

PMID- 16569740
TI  - Regulation of the human oxytocin receptor by nuclear factor-kappaB and
      CCAAT/enhancer-binding protein-beta.
AB  - CONTEXT: Increased myometrial sensitivity to oxytocin at term is mediated through
      increased oxytocin receptor (OTR) expression. OTR promoter contains putative
      transcription factor-binding sites for activating protein-1 (AP-1),
      CCAAT/enhancer-binding protein (C/EBP), and nuclear factor-kappaB (NF-kappaB),
      which may be activated by IL-1beta, whose concentrations increase with labor.
      OBJECTIVE: The objective of this study was to examine the effect of IL-1beta on
      OTR expression and the roles of AP-1, C/EBP, and NF-kappaB in OTR promoter
      function. RESULTS: IL-1beta induces an increase in OTR mRNA concentrations and
      OTR ligand binding in myometrial cells, which is maximal at 4 h and decreased
      after 20 h. IL-1beta activates the transcription factors AP-1 C/EBPbeta, and NF
      kappaB. Using computer-based analysis and EMSA studies, we have identified three
      AP-1, nine C/EBP, and three NF-kappaB DNA-binding sites in the OTR promoter. In
      transient transfection studies, OTR promoter activity was increased by C/EBPbeta
      and NF-kappaB, but not by AP-1. C/EBPbeta and NF-kappaB together had a
      synergistic action in the induction of OTR promoter activity. Site-directed
      mutagenesis of each individual C/EBP and NF-kappaB site had no effect on the
      ability of C/EBPbeta, NF-kappaB, or their combination to activate OTR promoter.
      However, mutation of both NF-kappaB sites inhibited promoter activation by NF
      kappaB alone, but not that by the combination of C/EBPbeta and NF-kappaB.
      Deletion studies showed that a region between -851 and -656 of the OTR confers
      responsiveness to the combination of C/EBPbeta and NF-kappaB. CONCLUSION: IL
      1beta has a biphasic effect on OTR expression in myometrial cells, and C/EBP and
      NF-kappaB play synergistic roles in OTR promoter activation.

PMID- 16569741
TI  - Insulin sensitivity, glucose effectiveness, and free fatty acid dynamics after
      human islet transplantation for type 1 diabetes.
AB  - CONTEXT: Islet transplantation results in impaired insulin secretion, but whether
      defects in insulin sensitivity contribute to impaired glucose disposal after
      islet transplantation under modern immunosuppression is not known. OBJECTIVE: Our
      objective was to evaluate insulin sensitivity after islet transplantation
      performed under tacrolimus-based immunosuppression that used minimal steroids.
      SETTING: This study was conducted at the University of Pennsylvania General
      Clinical Research Center. PARTICIPANTS: Eight islet transplant recipients, six
      type 1 diabetic (T1D), and 10 nondiabetic control subjects participated.
      INTERVENTION: We performed an insulin-modified frequently sampled iv glucose
      tolerance test to measure insulin sensitivity (S(I)), glucose effectiveness, and
      free fatty acid (FFA) dynamics. RESULTS: S(I) was significantly greater in the
      islet transplant and control groups, compared with the T1D group (P < 0.05 for
      both comparisons). Glucose effectiveness was not significantly different across
      all three groups but was lower by trend in the T1D and islet transplant groups,
      compared with the control group (P = 0.07 overall ANOVA). FFA levels suppressed
      normally in the transplant recipients, but the timing and magnitude of FFA
      suppression were significantly impaired in the T1D group, compared with the islet
      transplant and control groups (P < 0.05 for all comparisons). The acute insulin
      response to glucose and the disposition index (D(I) = acute insulin response to
      glucose x S(I)) were significantly lower in the islet transplant group, compared
      with the control group (P < 0.05 for all comparisons). CONCLUSIONS: These data
      suggest that even modest restoration of insulin secretion in islet transplant
      recipients may result in improved insulin sensitivity and FFA dynamics.

PMID- 16569742
TI  - Clinical and functional characteristics of the human Arg59Ter insulin-like growth
      factor i receptor (IGF1R) mutation: implications for a gene dosage effect of the
      human IGF1R.
AB  - CONTEXT: Signaling via the IGF-I receptor (IGF-IR) is crucial for normal prenatal
      and postnatal growth. The heterozygous IGF-IR mutation Arg59Ter resulted in
      reduced IGF-IR expression and represents haploinsufficiency of the human IGF1R
      gene. OBJECTIVE: We studied clinical and in vitro aspects of a human IGF1R gene
      dosage effect. We provide detailed clinical data on the two half-brothers and
      their mother with the Arg59Ter mutation. Arg59Ter and control fibroblasts were
      examined for functionality of IGF-I and insulin-stimulated receptor
      phosphorylation and signal transduction. RESULTS: The two brothers presented with
      primary microcephaly, mild mental retardation, and intrauterine as well as
      postnatal growth deficits. After GH therapy (30 microg/kg.d) for 24 months, the
      growth deficit in the propositus decreased by +1.0 sd. There was no clinical
      evidence for impaired glucose tolerance or hypoglycemia in all Arg59Ter subjects.
      In vitro, IGF-IR-deficient Arg59Ter cells expressed less IGF-IR and unchanged
      insulin receptor (IR) protein. Receptor autophosphorylation and phosphorylation
      of downstream protein kinase B/Akt exhibited resistance to IGF-I but showed an
      augmented response to insulin in Arg59Ter cells. Decreased IGF-IR content was
      accompanied by a reduction of IGF-IR/IR receptor hybrids, and therefore,
      increased levels of IR/IR homodimers probably explain increased insulin
      stimulated receptor autophosphorylation and Akt phosphorylation. CONCLUSIONS: In
      vivo and in vitro IGF-I resistance in Arg59Ter subjects and fibroblasts indicates
      a human IGF1R gene dosage effect involving not only the IGF-IR, but also IGF
      IR/IR hybrids. The abundance of both the IGF-IR protein and IGF-IR/IR hybrid
      receptors may have an impact on human growth, organ function, and glucose
      metabolism.

PMID- 16569743
TI  - A mutagenetic tree hidden Markov model for longitudinal clonal HIV sequence data.
AB  - RNA viruses provide prominent examples of measurably evolving populations. In
      human immunodeficiency virus (HIV) infection, the development of drug resistance
      is of particular interest because precise predictions of the outcome of this
      evolutionary process are a prerequisite for the rational design of antiretroviral
      treatment protocols. We present a mutagenetic tree hidden Markov model for the
      analysis of longitudinal clonal sequence data. Using HIV mutation data from
      clinical trials, we estimate the order and rate of occurrence of seven amino acid
      changes that are associated with resistance to the reverse transcriptase
      inhibitor efavirenz.

PMID- 16569744
TI  - The Society for Academic Emergency Medicine's 2004-2005 emergency medicine
      faculty salary and benefit survey.
AB  - OBJECTIVES: To report on the sixth survey of the Society for Academic Emergency
      Medicine (SAEM) of emergency medicine faculty salaries, benefits, work hours, and
      department demographics for all programs accredited by the Residency Review
      Committee for Emergency Medicine (RRC-EM). METHODS: Data represent compensation
      paid for the 2004-2005 academic year. Responses were collected by SAEM, and
      blinded program and individual faculty data were entered into a customized
      version of a relational database program with a built-in statistical package.
      Salary data were sorted by criteria such as program region, faculty title,
      American Board of Emergency Medicine certification, academic rank, years since
      completing residency, program size, and whether data were reported to the
      American Association of Medical Colleges (AAMC). Demographic data were analyzed
      with regard to numerous criteria including department staffing levels, emergency
      department (ED) volumes, ED length of stay, department income sources, salary
      incentive components, research funding, and specific type and value of fringe
      benefits offered. Data were compared with previous SAEM studies. RESULTS: Sixty
      one of 132 (46%) accredited programs responded, yielding data on 1,213 full-time
      faculty from all four AAMC regions. Mean salaries were reported as follows: all
      faculty, 189,848 dollars; first-year faculty, 153,855 dollars; programs reporting
      data to AAMC, 183,605 dollars; programs not reporting data to AAMC, 204,383
      dollars; core faculty, 197,259 dollars; and noncore faculty, 164,215 dollars.
      Mean salaries as reported by AAMC region were as follows: Northeast, 192,864
      dollars; South, 182,768 dollars; Midwest, 192,224 dollars; and West, 195,732
      dollars. Full-time emergency medicine residency program faculty are reported to
      be working an average of 1,032 total clinical hours per year. Workweeks average
      22 clinical hours per week and 22 nonclinical hours per week, with 5.1 weeks of
      time off per year. CONCLUSIONS: Reported salaries for full-time emergency
      medicine residency faculty continue to rise overall but fell for the first time
      in one region (the Midwest). Academic rank continues to correlate directly with
      salary. Fellowship training continues to show a negative correlation with salary.
      Significant regional differences in salaries have been present in all six SAEM
      surveys.

PMID- 16569746
TI  - Age effect on efficacy and side effects of two sedation and analgesia protocols
      on patients going through cardioversion: a randomized clinical trial.
AB  - BACKGROUND: Cardioversion (CV), a painful procedure, requires sedation and
      analgesia. Although several sedation agents currently are in use for CV, data on
      age-specific efficacy and side effects of midazolam and propofol have been
      limited. OBJECTIVES: To compare the efficacy and side effects of midazolam and
      propofol in patients of two different age groups, younger than 65 years and 65
      years and over, who were going through CV. METHODS: Seventy consented patients
      with CV indications caused by atrial fibrillation were included in this clinical
      trial. The participants were placed into four groups by using a stratified
      randomization method: patients aged younger than 65 years who were receiving
      midazolam (n = 12) or propofol (n = 11) and patients 65 years and over who were
      receiving midazolam (n = 25) or propofol (n = 22). Medications were administered
      by slow intermittent bolus injections. During CV, time to reach Ramsay Sedation
      Scale level 5 (RSS-5; induction time); time to reach RSS-2 (recovery time); and
      side effects including desaturation, apnea, and changes in hemodynamic parameters
      were recorded by a person blinded to the patient treatment allocation. RESULTS:
      Mean induction time was similar in all four groups. Mean recovery time (min +/-
      SD) was shorter in both propofol groups when compared with both midazolam groups:
      18.8 (+/- 4.06) and 40.33 (+/- 20.8) in the group younger than 65 years and 18.2
      (+/- 5.12) and 54.2 (+/- 20.85) in the group 65 years or older, respectively (p <
      0.001). Older participants in each medication group needed less medication than
      younger patients. There were no hemodynamic differences between the groups.
      Desaturation was higher in both midazolam groups as compared with individuals in
      the age-matched propofol groups (both p < 0.05). Patient reactions were less in
      propofol groups with similar joules during CV procedures than were those in the
      midazolam groups. CONCLUSIONS: Propofol appears to be a better choice for CV
      sedation in elders because of its short recovery time, fewer side effects, and
      its more comfortable sedative effect.

PMID- 16569747
TI  - Resident-as-teacher: a suggested curriculum for emergency medicine.
AB  - Resident teaching is a competency that must be recognized, developed, and
      assessed. The ACGME core competencies include the role of physician as educator
      to "educate patients and families" and to "facilitate the learning of students
      and other health care professionals." Residents spend a significant proportion of
      their time in teaching activities, and students report achieving much of their
      clinical learning from their interactions with residents. Although many residents
      enjoy their critical role as teacher, many do not feel well prepared to teach.
      This article summarizes a preliminary curriculum of modules for a resident
      teacher-training program for emergency medicine residents. The goal of these
      modules is to provide learning objectives and an initial structure through which
      residents could improve basic teaching skills. Many of these skills are adaptable
      to residents' interactions with each other and with students, other healthcare
      professionals, and patients. Each module and corresponding teaching exercises can
      be found at http://www.saem.org.

PMID- 16569748
TI  - Childhood soccer injuries treated in U.S. emergency departments.
AB  - OBJECTIVES: Soccer, an increasingly popular sport among children in the United
      States, is a common precipitant to injury-related emergency department (ED)
      visits. The authors estimated the number of children treated in EDs for soccer
      related injuries and described the nature of these injuries. METHODS: Data from
      the 2000 National Electronic Injury Surveillance System All Injury Program were
      used to estimate the overall number and rate of soccer injuries in children,
      calculate injury rates per 1,000 children, and describe the body regions affected
      and types of injuries. Results were stratified by five-year age groups (5-9
      years, 10-14 years, and 15-19 years). RESULTS: Approximately 144,600 children
      sustained soccer-related injuries in 2000 for a rate of 2.36 injuries per 1,000
      children. Injury rates increased with age (0.8, 5-9 year olds; 3.1, 10-14 year
      olds; 3.2, 15-19 year olds). Common types of injuries were strains/sprains
      (36.7%), fractures (23.0%), and contusions (20.9%). Fractures decreased with age;
      sprains/strains increased with age. Commonly injured body regions varied by age.
      Wrist and finger injuries were most common (12.7% and 12.4%, respectively) in the
      youngest group; in the 10-14-year-old group, ankle and wrist injuries were most
      common (15.7% and 13.6%, respectively). In the oldest age group, ankle injuries
      were most common (21.9%), followed by knee injuries (17.6%). CONCLUSIONS:
      Substantial numbers of children were treated in EDs for soccer-related injuries.
      Injury types and affected body regions varied by age. Injury prevention efforts
      to reduce soccer-related injuries may need to be age specific.

PMID- 16569749
TI  - Ten-year experience with an emergency medicine resident research project
      requirement.
AB  - BACKGROUND: Controversy exists regarding the value and quality of required
      emergency medicine (EM) resident scholarly projects. OBJECTIVES: To describe the
      research designs and presentation rate at national scientific meetings and the
      publication rate of EM resident scholarly projects at a university-based
      residency program. METHODS: The authors reviewed the initial ten years (1993
      2002) of resident scholarly projects from an EM residency program. Since the
      inception of the program, a formal research study has been required of all
      residents for residency graduation. Scholarly projects were reviewed and
      categorized by study design. Abstracts from the American Academy of Emergency
      Medicine (AAEM), American College of Emergency Physicians (ACEP), and Society for
      Academic Emergency Medicine (SAEM) annual meetings were searched to identify
      projects presented at any of these national meetings. A PubMed search for
      resident and faculty investigators was performed, and faculty and graduated
      residents were queried to identify all resident scholarly projects published in
      peer-reviewed journals. RESULTS: Eighty-seven residents produced 90 scholarly
      projects. Study designs were prospective data collection, 42 (47%); retrospective
      chart review, 38 (42%); survey, 5 (6%); animal, 4 (4%); and computer program
      development, 1 (1%). Of the 80 projects collecting patient data, 72 were
      conducted at a single center; 6, at two centers; and 2, at five centers each. Of
      the 42 prospective clinical studies, 27 (64%) were observational and 15 (36%)
      were interventional. Forty-six (51%) abstracts were presented at national
      meetings (SAEM, 20; ACEP, 19; AAEM, 3; and other, 4). Thirty-six (40%) of the
      projects have been published in peer-reviewed journals. Abstract presentation at
      national meetings (range, 13%-64% of projects per yr) and manuscript publication
      rates (range, 0-67% of projects per yr) were variable from year to year.
      CONCLUSIONS: Resident scholarly projects at one institution were equally likely
      to use a prospective or retrospective design, and most were conducted at a single
      center. More than half of the projects were presented at national research
      meetings, and more than a third were subsequently developed into manuscripts and
      published in peer-reviewed journals. When an original research study is required
      for satisfying the scholarly requirement for EM residency graduation, resident
      projects can contribute to the EM literature.

PMID- 16569750
TI  - Does end-tidal carbon dioxide monitoring detect respiratory events prior to
      current sedation monitoring practices?
AB  - OBJECTIVES: The value of ventilation monitoring with end-tidal carbon dioxide
      (ETCO2) to anticipate acute respiratory events during emergency department (ED)
      procedural sedation and analgesia (PSA) is unclear. The authors sought to
      determine if ETCO2 monitoring would reveal findings indicating an acute
      respiratory event earlier than indicated by current monitoring practices.
      METHODS: The study included a prospective convenience sample of ED patients
      undergoing PSA. Clinicians performed ED PSA procedures with generally accepted
      patient monitoring, including oxygen saturation (SpO2), and clinical ventilation
      assessment. A study investigator recorded ETCO2 levels and respiratory events
      during each PSA procedure, with clinical providers blinded to ETCO(2) levels.
      Acute respiratory events were defined as SpO2 < or =92%, increases in the amount
      of supplemental oxygen provided, use of bag-valve mask or oral/nasal airway for
      ventilatory assistance, repositioning or airway alignment maneuvers, and use of
      physical or verbal means to stimulate patients with depressed ventilation or
      apnea, and reversal agent administration. RESULTS: Enrollment was stopped after
      independent review of 20 acute respiratory events in 60 patient sedation
      encounters (33%). Abnormal ETCO2 findings were documented in 36 patients (60%).
      Seventeen patients (85%) with acute respiratory events demonstrated ETCO2
      findings indicative of hypoventilation or apnea during PSA. Abnormal ETCO2
      findings were documented before changes in SpO2 or clinically observed
      hypoventilation in 14 patients (70%) with acute respiratory events. CONCLUSIONS:
      Abnormal ETCO2 findings were observed with many acute respiratory events. A
      majority of patients with acute respiratory events had ETCO2 abnormalities that
      occurred before oxygen desaturation or observed hypoventilation.

PMID- 16569751
TI  - Ventricular fibrillation in pediatric cardiac arrest.
AB  - OBJECTIVES: After activating 9-1-1 for out-of-hospital cardiac arrest (CA),
      guidelines for children 1 year and older have evolved to include immediate
      automated external defibrillator (AED) use for witnessed arrest, and two minutes
      of cardiopulmonary resuscitation (CPR) followed by AED use for unwitnessed
      arrests. The best approach to resuscitation in a two-tiered emergency medical
      services (EMS) system depends in part on how likely the patient is to present
      with ventricular fibrillation (VF). Therefore, the authors evaluated the
      frequency of VF with respect to age and other characteristics to further
      elucidate the role of the AED among pediatric CAs. METHODS: The investigation was
      a retrospective cohort study of EMS-treated, nontraumatic, out-of-hospital CA
      among persons aged 1-18 years in King County, Washington, between April 1, 1976,
      and December 31, 2003. The primary goal was to identify the proportion of
      patients presenting to EMS in VF, according to age. The association between other
      characteristics and the likelihood of VF was also evaluated. Finally, hospital
      survival according to cardiac rhythm at EMS arrival was evaluated. RESULTS:
      Ventricular fibrillation was the presenting rhythm in 17.6% of cases (48/272).
      The proportion presenting with VF was 7.6% (10/131) among children aged 1-7 years
      and 27.0% (38/141) among children aged 8-18 years (p < 0.001). In multivariable
      models, VF was independently associated with age 8 years and older compared with
      1-7 years (odds ratio, 3.19; 95% confidence interval [CI] = 1.46 to 6.97),
      witnessed arrest (odds ratio, 3.33; 95% CI = 1.63 to 6.82), and cardiac etiology
      (odds ratio, 2.89; 95% CI = 1.32 to 6.34). Survival was 31.3% (15/48) for VF and
      10.7% (24/224) for nonshockable rhythm CAs. CONCLUSIONS: The proportion of
      children aged younger than 8 years presenting with VF is low compared with older
      children. The greatest increase in VF proportion occurs in children older than 12
      years. Based on these results, the best approach for initial EMS resuscitation in
      a two-tiered EMS system, CPR versus AED use, is uncertain among younger children.
      Inclusion of witness status into the decision process for younger children may
      more efficiently allocate AED use, a finding in accordance with 2005 guidelines.

PMID- 16569752
TI  - Augmentation of Cav3.2 T-type calcium channel activity by cAMP-dependent protein
      kinase A.
AB  - Ca2+ influx through T-type Ca2+ channels is crucial for important physiological
      activities such as hormone secretion and neuronal excitability. However, it is
      not clear whether these channels are regulated by cAMP-dependent protein kinase A
      (PKA). In the present study, we examined whether PKA modulates Cav3.2 T-type
      channels reconstituted in Xenopus oocytes. Application of 10 microM forskolin, an
      adenylyl cyclase stimulant, increased Cav3.2 channel activity by 40+/-4% over 30
      min and negatively shifted the steady-state inactivation curve (V50=-61.4+/-0.2
      versus -65.5+/-0.1 mV). Forskolin did not affect other biophysical properties of
      Cav3.2 channels, including activation curve, current kinetics, and recovery from
      inactivation. Similar stimulation was achieved by applying 200 microM 8-bromo
      cAMP, a membrane-permeable cAMP analog. The augmentation of Cav3.2 channel
      activity by forskolin was strongly inhibited by preincubation with 20 microM N-[2
      (4-bromocinnamylamino)ethyl]-5-isoquinoline (H89), and reversed by subsequent
      application of 500 nM protein kinase A inhibitor peptide. The stimulation of
      Cav3.2 channel activity by PKA was mimicked by serotonin when 5HT7 receptor was
      coexpressed with Cav3.2 in Xenopus oocytes. Finally, using chimeric channels
      constructed by replacing individual cytoplasmic loops of Cav3.2 with those of the
      Nav1.4 channel, which is insensitive to PKA, we localized a region required for
      the PKA-mediated augmentation to the II-III loop of the Cav3.2.

PMID- 16569753
TI  - Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of
      anxiety: further evidence for an anxiolytic role for endogenous cannabinoid
      signaling.
AB  - Extracts of Cannabis sativa have been used for their calming and sedative effects
      for centuries. Recent developments in drug discovery have suggested that
      modulation of neuronal endogenous cannabinoid signaling systems could represent a
      novel approach to the treatment of anxiety-related disorders while minimizing the
      adverse effects of direct acting cannabinoid receptor agonists. In this study, we
      evaluated the effects of direct cannabinoid receptor agonists and antagonists and
      endocannabinoid-modulating drugs on anxiety-like behavior in mice using the
      elevated-plus maze. We found that the direct CB1 receptor agonists (1R,3R,4R)-3
      [2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol (CP
      55,940) (0.001-0.3 mg/kg) and 2,3-dihydro-5-methyl-3[(4
      morpholinyl)methyl]pyrrolo [1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone
      mesylate) (WIN 55212-2) (0.3-10 mg/kg) increased time spent on the open arms (To)
      at low doses only. At the highest doses tested, both compounds altered overall
      locomotor activity. In contrast, Delta9-tetrahydrocannabinol (0.25-10 mg/kg)
      produced a dose-dependent reduction in To. The endocannabinoid uptake/catabolism
      inhibitor 4-hydroxyphenylarachidonylamide (AM404) (0.3-10 mg/kg) produced an
      increase in To at low doses and had no effect at the highest dose tested. The
      fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3'-carbamoyl
      biphenyl-3-yl ester (URB597) (0.03-0.3 mg/kg) produced a monophasic, dose
      dependent increase in To. The CB1 receptor antagonists N-(piperidin-1-yl)-5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl
      (SR141716) (1-10 mg/kg) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) (1-10 mg/kg) produced
      dose-related decreases in To. These data indicate that activation of CB1
      cannabinoid receptors reduces anxiety-like behaviors in mice and further support
      an anxiolytic role for endogenous cannabinoid signaling. These results suggest
      that pharmacological modulation of this system could represent a new approach to
      the treatment of anxiety-related psychiatric disorders.

PMID- 16569754
TI  - Enhanced xenobiotic-induced hepatotoxicity and Kupffer cell activation by
      restraint-induced stress.
AB  - We tested the hypothesis that environmental stress is a predisposing factor for
      liver injury by examining the effect of acute restraint on liver injury provoked
      by carbon tetrachloride (CCl4) and allyl alcohol. Mice were immobilized using
      Plexiglas restraint cages, producing a form of psychogenic stress, whereas other
      animals were allowed to roam free. Serum alanine aminotransferase levels were
      elevated significantly in restrained animals after administration of varying
      doses of CCl4 or allyl alcohol that did not produce liver injury in unrestrained
      animals. This enhanced liver injury after CCl4 was seen in both male and female
      mice. The duration of acute restraint was found to be important because a period
      of 2.5 h of restraint enhanced hepatotoxicity, whereas shorter periods of
      restraint did not significantly increase liver injury. Serum corticosterone
      concentrations increased, whereas hepatic glutathione content decreased during
      and after acute restraint. In addition, delay in administration of CCl4 until 5 h
      after completion of restraint also produced an elevated level of liver injury
      compared with that seen in free roaming animals. Immunohistochemical examination
      of the livers showed significantly enhanced Kupffer cell activation in restrained
      mice compared with that of free roaming mice. These observations suggest that
      induction of psychogenic stress may increase the susceptibility to liver injury
      observed with classic hepatotoxicants and may represent an important predisposing
      factor to liver injury after xenobiotic exposure. The underlying mechanism seems
      to be increased macrophage activation in the liver, which may subsequently
      sensitize hepatocytes to xenobiotics and thus enhance hepatotoxicity.

PMID- 16569755
TI  - Paradoxical effects of hydrogen peroxide on human airway anion secretion.
AB  - The present study concerns intriguing effects of hydrogen peroxide (H2O2) on cAMP
      mediated anion secretion in polarized human airway epithelia. Although H2O2
      applied to the apical and basolateral membrane increases short-circuit currents
      (ISC) with analogous properties, it has opposite effects on subsequent cAMP
      activated ISC responses. Namely, forskolin (FK)-induced ISC responses were down
      regulated by the apical presence of H2O2, whereas they were up-regulated by its
      basolateral presence. Despite this contrasting effect, oxidative stimuli from
      either aspect of the monolayer hindered FK-induced increments in cytosolic cAMP
      levels and apical membrane Cl- conductance. The site-dependent effects of H2O2
      were reproduced in the responses to 8-bromo-cAMP. Estimation of the anionic
      composition of the ISC revealed that the FK up-regulated both bumetanide [an Na+
      K+-2Cl- cotransporter (NKCC1) inhibitor]-sensitive and 4,4'-dinitrostilbene-2,2'
      disulfonic acid [an HCO3--dependent anion transporter (NBC1/AE2) inhibitor]
      sensitive ISC in the control, whereas the up-regulation evidently favored
      bumetanide-sensitive ISC in the basolateral presence of H2O2. The FK-induced
      NKCC1 augmentation after exposure to basolateral H2O2 was counteracted by
      cytochalasin D, an inhibitor of microfilament function, but not by charybdotoxin,
      a blocker of the intermediate conductance Ca2+-activated K+ channel, whose
      activation could be related to NKCC1-mediated Cl- secretion. These observations
      suggest that basolaterally but not apically applied H2O2 potentiates subsequent
      cAMP-mediated Cl- secretion by an increase in Cl- uptake via basolateral NKCC1,
      whose sensitivities to cAMP/protein kinase A are up-regulated, overcoming the
      H2O2-induced inhibition of cAMP-mediated apical anion conductance. The
      basolateral membrane-specific effects of H2O2 may be relevant to the basolateral
      cytoskeleton, which is believed to interact with NKCC1.

PMID- 16569756
TI  - Increased RhoA/Rho-kinase signaling mediates spontaneous tone in aorta from
      angiotensin II-induced hypertensive rats.
AB  - Spontaneous tone in large arteries may contribute to the pathogenesis of
      hypertension. Reactive oxygen species and Ca2+ influx have been shown to
      stimulate the development of spontaneous tone in isolated aortic rings in several
      models of hypertensive rats. The aim of this study was to investigate the role of
      the RhoA/Rho-kinase signaling pathway in the development of spontaneous tone in
      angiotensin II-induced hypertension and to explore the underlying mechanisms of
      RhoA/Rho-kinase activation. Our results showed that spontaneous tone was greatly
      enhanced in endothelium-denuded aortic rings from angiotensin II-induced
      hypertensive rats compared with their normotensive counterparts (73+/-5 versus
      7+/-3% of phenylephrine-induced maximal contraction, respectively). The Rho
      kinase inhibitor (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)
      cyclohexanecarboxamide (Y-27632) (0.1-10 microM) concentration dependently
      inhibited spontaneous tone in aortic rings from angiotensin II-treated rats.
      NADPH oxidase inhibitors diphenylene iodonium and apocynin also significantly
      reduced spontaneous tone. Chronic angiotensin II treatment markedly increased
      RhoA protein expression (57%) but had no effect on Rho guanine nucleotide
      exchange factor mRNA or Rho-kinase protein expression levels. In endothelium
      denuded rings from normotensive rats, angiotensin II (100 nM) increased RhoA
      membrane translocation and phosphorylation of the myosin light chain phosphatase
      target subunit, which were both blocked by the NADPH oxidase inhibitor
      diphenylene iodonium (10 microM). In conclusion, these data suggest that chronic
      treatment with angiotensin II leads to up-regulation of the RhoA/Rho-kinase
      pathway, contributing to spontaneous tone development in rat aorta. Increased
      NADPH oxidase-dependent reactive oxygen species may be one of the mechanisms
      mediating the RhoA/Rho-kinase activation.

PMID- 16569757
TI  - Thienorphine is a potent long-acting partial opioid agonist: a comparative study
      with buprenorphine.
AB  - A strategy in the development of new treatment for opioid addiction is to find
      partial opioid agonists with properties of long duration of action and high oral
      bioavailability. In a search for such compounds, thienorphine, a novel analog of
      buprenorphine, was synthesized. Here, we reported that, like buprenorphine,
      thienorphine bound potently and nonselectively to mu-, delta-, and kappa-opioid
      receptors stably expressed in CHO (Chinese hamster ovary) cells and behaved as a
      partial agonist at mu-opioid receptor. However, some differences were observed
      between the pharmacological profiles of thienorphine and buprenorphine. In vitro,
      thienorphine was more potent than buprenorphine in inhibiting [3H]diprenorphine
      and stimulating guanosine 5'-O-(3-[35S]thio)triphosphate binding to rat mu-opioid
      receptor stably expressed in CHO cells. In vivo, thienorphine exhibited a less
      potent but more efficacious antinociceptive effect with an ED50 value of 0.25
      mg/kg s.c. and more potent antimorphine effect with an ED50 value of 0.64 mg/kg
      intragastric, compared with buprenorphine. Additionally, the bioavailability of
      thienorphine was greatly higher than that of buprenorphine after oral
      administration. Moreover, compared with buprenorphine, thienorphine showed a
      similar long-lasting antinociceptive effect but a much longer antagonism of
      morphine-induced lethality (more than 15 days). These results indicate that
      thienorphine is a potent, long-acting partial opioid agonist with high oral
      bioavailability and may have possible application in treating addiction.

PMID- 16569758
TI  - Decreased nutrient-stimulated insulin secretion in chronically hypoglycemic late
      gestation fetal sheep is due to an intrinsic islet defect.
AB  - We measured in vivo and in vitro nutrient-stimulated insulin secretion in late
      gestation fetal sheep to determine whether an intrinsic islet defect is
      responsible for decreased glucose-stimulated insulin secretion (GSIS) in response
      to chronic hypoglycemia. Control fetuses responded to both leucine and lysine
      infusions with increased arterial plasma insulin concentrations (average
      increase: 0.13 +/- 0.05 ng/ml leucine; 0.99 +/- 0.26 ng/ml lysine). In vivo
      lysine-stimulated insulin secretion was decreased by chronic (0.37 +/- 0.18
      ng/ml) and acute (0.27 +/- 0.19 ng/ml) hypoglycemia. Leucine did not stimulate
      insulin secretion following acute hypoglycemia but was preserved with chronic
      hypoglycemia (0.12 +/- 0.09 ng/ml). Isolated pancreatic islets from chronically
      hypoglycemic fetuses had normal insulin and DNA content but decreased fractional
      insulin release when stimulated with glucose, leucine, arginine, or lysine.
      Isolated islets from control fetuses responded to all nutrients. Therefore,
      chronic late gestation hypoglycemia causes defective in vitro nutrient-regulated
      insulin secretion that is at least partly responsible for diminished in vivo
      GSIS. Chronic hypoglycemia is a feature of human intrauterine growth restriction
      (IUGR) and might lead to an islet defect that is responsible for the decreased
      insulin secretion patterns seen in human IUGR fetuses and low-birth-weight human
      infants.

PMID- 16569759
TI  - The vascular endothelial cell mediates insulin transport into skeletal muscle.
AB  - The pathways by which insulin exits the vasculature to muscle interstitium have
      not been characterized. In the present study, we infused FITC-labeled insulin to
      trace morphologically (using confocal immunohistochemical methods) insulin
      transport into rat skeletal muscle. We biopsied rectus muscle at 0, 10, 30, and
      60 min after beginning a continuous (10 mU x min(-1) x kg(-1)), intravenous FITC
      insulin infusion (with euglycemia maintained). The FITC-insulin distribution was
      compared with that of insulin receptors (IR), IGF-I receptors (IGF-IR), and
      caveolin-1 (a protein marker for caveolae) in skeletal muscle vasculature. We
      observed that muscle endothelium stained strongly for FITC-insulin within 10 min,
      and this persisted to 60 min. Endothelium stained more strongly for FITC-insulin
      than any other cellular elements in muscle. IR, IGF-IR, and caveolin-1 were also
      detected immunohistochemically in muscle endothelial cells. We further compared
      their intracellular distribution with that of FITC-insulin in cultured bovine
      aortic endothelial cells (bAECs). Considerable colocalization of IR or IGF-IR
      with FITC-insulin was noted. There was some but less overlap of IR or IGF-IR or
      FITC-insulin with caveolin-1. Immunoprecipitation of IR coprecipitated caveolin
      1, and conversely the precipitation of caveolin-1 brought down IR. Furthermore,
      insulin increased the tyrosine phosphorylation of caveolin-1, and filipin (which
      inhibits caveolae formation) blocked insulin uptake. Finally, the ability of
      insulin, IGF-I, and IGF-I-blocking antibody to diminish insulin transport across
      bAECs grown on transwell plates suggested that IGF-IR, in addition to IR, can
      also mediate transendothelial insulin transit. We conclude that in vivo
      endothelial cells rapidly take up and concentrate insulin relative to plasma and
      muscle interstitium and that IGF-IR, like IR, may mediate insulin transit through
      endothelial cells in a process involving caveolae.

PMID- 16569760
TI  - Cationic amino acid transport across the blood-brain barrier is mediated
      exclusively by system y+.
AB  - Cationic amino acid (CAA) transport is brought about by two families of proteins
      that are found in various tissues: Cat (CAA transporter), referred to as system
      y+, and Bat [broad-scope amino acid (AA) transporter], which comprises systems
      b0,+, B0,+, and y+L. CAA traverse the blood-brain barrier (BBB), but experiments
      done in vivo have only been able to examine the BBB from the luminal (blood
      facing) side. In the present study, plasma membranes isolated from bovine brain
      microvessels were used to identify and characterize the CAA transporter(s) on
      both sides of the BBB. From these studies, it was concluded that system y+ was
      the only transporter present, with a prevalence of activity on the abluminal
      membrane. System y+ was voltage dependent and had a Km of 470 +/- 106 microM (SE)
      for lysine, a Ki of 34 microM for arginine, and a Ki of 290 microM for ornithine.
      In the presence of Na+, system y+ was inhibited by several essential neutral AAs.
      The Ki values were 3-10 times the plasma concentrations, suggesting that system
      y+ was not as important a point of access for these AAs as system L1. Several
      small nonessential AAs (serine, glutamine, alanine,and glycine) inhibited system
      y+ with Ki values similar to their plasma concentrations, suggesting that system
      y+ may account for the permeability of the BBB to these AAs. System y+ may be
      important in the provision of arginine for NO synthesis. Real-time PCR and
      Western blotting techniques established the presence of the three known nitric
      oxide synthases in cerebral endothelial cells: NOS-1 (neuronal), NOS-2
      (inducible), and NOS-3 (endothelial). These results confirm that system y+ is the
      only CAA transporter in the BBB and suggest that NO can be produced in brain
      endothelial cells.

PMID- 16569761
TI  - The Rieske protein: a case study on the pitfalls of multiple sequence alignments
      and phylogenetic reconstruction.
AB  - Previously published phylogenetic trees reconstructed on "Rieske protein"
      sequences frequently are at odds with each other, with those of other subunits of
      the parent enzymes and with small-subunit rRNA trees. These differences are shown
      to be at least partially if not completely due to problems in the reconstruction
      procedures. A major source of erroneous Rieske protein trees lies in the presence
      of a large, poorly conserved domain prone to accommodate very long insertions in
      well-defined structural hot spots substantially hampering multiple alignments.
      The remaining smaller domain, in contrast, is too conserved to allow distant
      phylogenies to be deduced with sufficient confidence. Three-dimensional
      structures of representatives from this protein family are now available from
      phylogenetically distant species and from diverse enzymes. Multiple alignments
      can thus be refined on the basis of these structures. We show that structurally
      guided alignments of Rieske proteins from Rieske-cytochrome b complexes and
      arsenite oxidases strongly reduce conflicts between resulting trees and those
      obtained on their companion enzyme subunits. Further problems encountered during
      this work, mainly consisting in database errors such as wrong annotations and
      frameshifts, are described. The obtained results are discussed against the
      background of hypotheses stipulating pervasive lateral gene transfer in
      prokaryotes.

PMID- 16569763
TI  - ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell
      development and affects antigen presentation to CD4+ T cells.
AB  - Interferon consensus sequence-binding protein (ICSBP)/interferon regulatory
      factor 8 (IRF-8) is a transcription factor that plays critical roles in the
      differentiation of defined dendritic-cell (DC) populations and in the immune
      response to many pathogens. In this study, we show that splenic DCs (s-DCs) from
      ICSBP(-/-) mice are markedly defective in their ability to capture and to present
      exogenous antigens (Ags) to naive CD4(+) T lymphocytes. We found that CD8alpha(+)
      DCs and, to a lesser extent, CD8alpha(-) DCs from ICSBP(-/-) mice are impaired at
      internalizing Ags, either through a receptor-mediated pathway or by
      macropinocytosis, in spite of having a more immature phenotype than their wild
      type (WT) counterparts. These features reflected a greatly impaired ability of
      ICSBP(-/-) s-DCs to present injected soluble ovalbumin (OVA) to OVA-specific
      CD4(+) T cells in vivo. Conversely, bone marrow (BM)-derived DCs from ICSBP(-/-)
      mice, in keeping with their immature phenotype, exhibited higher endocytic
      activity than WT cells. However, Ag-loaded ICSBP(-/-) BM-DCs were defective in
      priming Ag-specific CD4(+) T lymphocytes and failed to induce a contact
      hypersensitivity (CHS) response when injected into competent WT hosts. Together,
      these results indicate that, throughout the developmental program of DCs, ICSBP
      differentially controls Ag uptake and MHC class II (MHC-II) presentation
      affecting both functions only in differentiated peripheral DCs.

PMID- 16569764
TI  - Enhanced purification of fetal liver hematopoietic stem cells using SLAM family
      receptors.
AB  - Although adult mouse hematopoietic stem cells (HSCs) have been purified to near
      homogeneity, it remains impossible to achieve this with fetal HSCs. Adult HSC
      purity recently has been enhanced using the SLAM family receptors CD150, CD244,
      and CD48. These markers are expressed at different stages of the hematopoiesis
      hierarchy, making it possible to highly purify adult HSCs as CD150(+)CD48(
      )CD244(-) cells. We found that SLAM family receptors exhibited a similar
      expression pattern in fetal liver. Fetal liver HSCs were CD150(+)CD48(-)CD244(-),
      and the vast majority of colony-forming progenitors were CD48(+)CD244(-)CD150(-)
      or CD48(+)CD244(+)CD150(-), just as in adult bone marrow. SLAM family markers
      enhanced the purification of fetal liver HSCs. Whereas 1 (11%) of every 8.9
      Thy(low)Sca-1(+)lineage(-)Mac-1(+) fetal liver cells gave long-term multilineage
      reconstitution in irradiated mice, 1 (18%) of every 5.7 CD150(+)CD48(-)CD41(-)
      cells and 1 (37%) of every 2.7 CD150(+)CD48(-)Sca-1(+)lineage(-)Mac-1(+) fetal
      liver cells gave long-term multilineage reconstitution. These data emphasize the
      robustness with which SLAM family markers distinguish progenitors at different
      stages of the hematopoiesis hierarchy and enhance the purification of definitive
      HSCs from diverse contexts. Nonetheless, CD150, CD244, and CD48 are not pan-stem
      cell markers, as they were not detectably expressed by stem cells in the fetal or
      adult nervous system.

PMID- 16569765
TI  - Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53
      dependent senescence.
AB  - The antiviral thymidine analog azidothymidine (AZT) is used to treat several
      virus-associated human cancers. However, to date the mechanism of AZT action
      remains unclear and thus, reasons for treatment failure are unknown. Adult T-cell
      leukemia/lymphoma (ATL) is an aggressive malignancy of poor prognosis. Here, we
      report that enduring AZT treatment of T-cell leukemia virus I-infected cells, in
      vitro and in vivo in ATL patients, results in inhibition of telomerase activity,
      progressive telomere shortening, and increased p14(ARF) expression. In turn, this
      elicits stabilization and reactivation of the tumor suppressor p53-dependent
      transcription, increased expression of the cyclin-dependent kinase inhibitor
      p21(Waf1), and accumulation of p27(kip1), thereby inducing cellular senescence
      and tumor cell death. While ATL patients carrying a wild-type p53 enter remission
      following treatment with AZT, those with a mutated p53 did not respond, and
      patients' disease relapse was associated with the selection of a tumor clone
      carrying mutated inactive p53.

PMID- 16569766
TI  - The neuropathologic phenotype of experimental ovine BSE is maintained after blood
      transfusion.
AB  - Iatrogenic transmission by blood transfusion has been described in cases of human
      variant Creutzfeldt-Jakob disease (vCJD), experimental ovine bovine spongiform
      encephalopathy (BSE), and natural sheep scrapie, demonstrating that blood in
      these prion diseases is infectious. However, the possible effect of the
      transfusion, derived from differences in the inoculum (blood) and the route of
      infection (intravenous), on the pathologic phenotype of the disease in the
      recipients is not known. This study describes the neuropathologic phenotype of
      PrP(d) accumulation in sheep succumbing to neurologic disease after blood
      transfusion from donors experimentally infected with BSE; these were either
      clinically or subclinically affected at the time of donation. We demonstrate that
      blood can become infectious at early stages of ovine BSE infection and that the
      PrP(d) immunohistochemical phenotype is maintained after transfusion. This
      suggests that a change in the pathologic phenotype of vCJD would not be expected
      as a result of exposure to infected blood.

PMID- 16569767
TI  - Differential regulation of T-cell growth by IL-2 and IL-15.
AB  - Although interleukin 2 (IL-2) and IL-15 signal through the common gamma chain
      (gammac) and through IL-2 receptor beta-chain (CD122) subunits, they direct
      distinct physiologic and immunotherapeutic responses in T cells. The present
      study provides some insight into why IL-2 and IL-15 differentially regulate T
      cell function by revealing that these cytokines are strikingly distinct in their
      ability to control protein synthesis and T-cell mass. IL-2 and IL-15 are shown to
      be equivalent mitogens for antigen-stimulated CD8(+) T cells but not for
      equivalent growth factors. Antigen-primed T cells cannot autonomously maintain
      amino acid incorporation or de novo protein synthesis without exogenous cytokine
      stimulation. Both IL-2 and IL-15 induce amino acid uptake and protein synthesis
      in antigen-activated T cells; however, the IL-2 response is strikingly more
      potent than the IL-15 response. The differential action of IL-2 and IL-15 on
      amino acid uptake and protein synthesis is explained by temporal differences in
      signaling induced by these 2 cytokines. Hence, the present results show that
      cytokines that are equivalent mitogens can have different potency in terms of
      regulating protein synthesis and cell growth.

PMID- 16569768
TI  - Proteasome-dependent down-regulation of activated Stat5A in the nucleus.
AB  - A broad spectrum of cytokines can activate the signal transducer and activator of
      transcription 5 (Stat5) by inducing a single tyrosine phosphorylation of the
      molecule. Although the process of Stat5 activation has been well studied, the
      mechanism by which it is inactivated is not fully understood. We demonstrate that
      the proteasome inhibitor MG132, but not the nuclear export inhibitor leptomycin B
      (LMB), stabilizes active nuclear Stat5A, whereas MG132 only partially stabilizes
      active cytoplasmic Stat5A. Importantly, ubiquitinated Stat5A is detected in the
      nucleus and the polyubiquitination of active Stat5A is K48 linked, a linkage type
      targeting proteins for degradation. Ubiquitination of Stat5A is recapitulated in
      a cell-free system, and Ubc5 is identified as the E2-conjugating enzyme for
      Stat5A ubiquitination. Interestingly, phosphorylation of Stat5A per se is not
      required for ubiquitination. Finally, C-terminal deletion analysis of Stat5A
      localizes the amphipathic region of amino acids 751-762 as a ubiquitination
      signal, possibly representing an E3 recognition motif. Taken together, these
      results demonstrate that the down-regulation of nuclear and cytoplasmic active
      Stat5A is differentially regulated. In the nucleus, ubiquitin/proteasome-mediated
      protein degradation is the dominant mechanism for the down-regulation of active
      Stat5A, whereas in the cytoplasm, protein tyrosine phasphatase is a major player
      in the down-regulation of active Stat5A.

PMID- 16569770
TI  - Gimap4 accelerates T-cell death.
AB  - Gimap4, a member of the newly identified GTPase of the immunity-associated
      protein family (Gimap), is strongly induced by the pre-T-cell receptor in
      precursor T lymphocytes, transiently shut off in double-positive thymocytes, and
      reappears after TCR-mediated positive selection. Here, we show that Gimap4
      remains expressed constitutively in the cytosol of mature T cells. A C-terminal
      IQ domain binds calmodulin in the absence of calcium, and conserved PKC
      phosphorylation motifs are targets of concanavalin A (ConA)- or PMA/ionomycin
      induced PKC activation. To address the role of Gimap4 in T-cell physiology, we
      completed the genomic organization of the gimap4 locus and generated a Gimap4
      null mutant mouse. Studies in these mice revealed no critical role of Gimap4 in T
      cell development but in the regulation of apoptosis. We have found that Gimap4
      accelerates the execution of programmed cell death induced by intrinsic stimuli
      downstream of caspase-3 activation and phosphatidylserine exposure. Apoptosis
      directly correlates with the phosphorylation status of Gimap4.

PMID- 16569769
TI  - Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6
      and its combination with unmodified anti-Tac (daclizumab) directed toward CD25.
AB  - Adult T-cell leukemia (ATL) consists of an overabundance of T cells, which
      express CD25. Therapeutic efficacy of astatine-211 ((211)At)-labeled murine
      monoclonal antibody 7G7/B6 alone and in combination with daclizumab was evaluated
      in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice given
      injections of MET-1 human T-cell leukemia cells. Daclizumab and 7G7/B6 are
      directed toward different epitopes of CD25. Either a single dose of 12 microCi
      (0.444 MBq) (211)At-7G7/B6 per mouse given intravenously or receptor-saturating
      doses of daclizumab given at 100 microg weekly for 4 weeks intravenously
      inhibited tumor growth as monitored by serum levels of human beta-2 microglobulin
      (beta(2)mu) and by prolonged survival of leukemia-bearing mice compared with the
      control groups (P < .001). The combination of 2 agents enhanced the antitumor
      effect when compared with groups treated with 12 microCi (0.444 MBq) of (211)At
      7G7/B6 (P < .05) or daclizumab alone (P < .05). The median survival duration of
      the PBS group was 62.6 days and 61.5 days in the radiolabeled nonspecific
      antibody (211)At-11F11-treated group. In contrast, 91% of mice in the combination
      group survived through day 94. These results that demonstrate a significantly
      improved therapeutic efficacy by combining (211)At-7G7/B6 with daclizumab support
      a clinical trial of this regimen in patients with ATL.

PMID- 16569771
TI  - FVIII production by human lung microvascular endothelial cells.
AB  - While extrahepatic factor VIII (FVIII) synthesis suffices for hemostasis, the
      extrahepatic production sites are not well defined. We therefore investigated the
      ability of the human lungs to produce FVIII. Lungs from heart-beating donors who
      were declined for transplantation were perfused and ventilated in an isolated
      reperfusion model for 2 hours. A progressive accumulation of FVIII and von
      Willebrand factor (VWF) was recorded in the perfusion medium in 3 of 4
      experiments. By contrast, factor V, fibrinogen, and immunoglobulin G (IgG) levels
      remained constant during the perfusion period, indicating that the accumulation
      of FVIII and VWF was not due to diffusion from the intercellular medium into the
      vascular system. Purified human lung microvascular endothelial cells produced
      FVIII during at least 2 passages in vitro. Altogether, these data identify the
      lung endothelial cells as a FVIII production site in humans.

PMID- 16569772
TI  - Enhancement of ligand-dependent activation of human natural killer T cells by
      lenalidomide: therapeutic implications.
AB  - Natural killer T (NKT) cells are CD1d-restricted glycolipid reactive innate
      lymphocytes that play an important role in protection from pathogens and tumors.
      Pharmacologic approaches to enhance NKT cell function will facilitate specific
      NKT targeting in the clinic. Here we show that lenalidomide (LEN), a novel
      thalidomide (Thal) analog, enhances antigen-specific expansion of NKT cells in
      response to the NKT ligand alpha-galactosylceramide (alpha-GalCer) in both
      healthy donors and patients with myeloma. NKT cells activated in the presence of
      LEN have greater ability to secrete interferon-gamma. Antigen-dependent
      activation of NKT cells was greater in the presence of dexamethasone (DEX) plus
      LEN than with DEX alone. Therapy with LEN/Thal also led to an increase in NKT
      cells in vivo in patients with myeloma and del5q myelodysplastic syndrome.
      Together these data demonstrate that LEN and its analogues enhance CD1d-mediated
      presentation of glycolipid antigens and support combining these agents with NKT
      targeted approaches for protection against tumors.

PMID- 16569773
TI  - Activation-independent, antibody-mediated removal of GPVI from circulating human
      platelets: development of a novel NOD/SCID mouse model to evaluate the in vivo
      effectiveness of anti-human platelet agents.
AB  - GPVI is a 62-kDa membrane glycoprotein expressed in noncovalent association with
      the Fc receptor gamma chain on human and murine platelets and serves as the major
      activating receptor for collagen. GPVI-specific antibodies have the capacity to
      specifically deplete GPVI from mouse and human platelets in vivo, rendering them
      unresponsive to collagen and GPVI-specific agonists. Such antibodies do not
      remove GPVI from noncirculating platelets in vitro, however, making it difficult
      to evaluate their antithrombotic potential and mechanism of action, particularly
      in human platelets. We devised a model system in which human platelets are
      introduced into the retroorbital plexus of nonobese diabetic/severe combined
      immunodeficient (NOD/SCID) mice, allowed to circulate, and evaluated for the
      effects of GPVI-specific murine monoclonal antibodies (mAbs) on platelet survival
      and function. GPVI-specific mAbs triggered depletion of GPVI from human, but not
      murine, platelets. Soluble truncated human GPVI appeared concomitantly in mouse
      plasma. GPVI-depleted human platelets had markedly diminished responses to GPVI
      specific agonists and unexpectedly exhibited somewhat depressed responses to G
      protein-coupled agonists. The ability to evaluate in living mice the in vivo
      function and survival of circulating human platelets may prove valuable for
      determining mechanisms of antibody-mediated platelet passivation and aid in the
      development of novel anti-platelet therapeutics.

PMID- 16569774
TI  - Genetic segregation of airway disease traits despite redundancy of calcium
      activated chloride channel family members.
AB  - Complex airway diseases such as asthma and chronic obstructive pulmonary disease
      exhibit stereotyped traits (especially airway hyperreactivity and mucous cell
      metaplasia) that are variably expressed in each patient. Here, we used a mouse
      model for virus-induced long-term expression of these traits to determine whether
      individual traits can be genetically segregated and thereby linked to separate
      determinants. We showed that an F2 intercross population derived from susceptible
      and nonsusceptible mouse strains can manifest individual phenotypic extremes that
      exhibit one or the other disease trait. Functional genomic analysis of these
      extremes further indicated that a member of the calcium-activated chloride
      channel (CLCA) gene family designated mClca3 was inducible with mucous cell
      metaplasia but not airway hyperreactivity. In confirmation of this finding, we
      found that mClca3 gene transfer to mouse airway epithelium was sufficient to
      induce mucous cell metaplasia but not airway hyperreactivity. However, newly
      developed mClca3(-/-) mice exhibited the same degree of mucous cell metaplasia
      and airway hyperreactivity as wild-type mice. Bioinformatic analysis of the Clca
      locus led to the identification of mClca5, and gene transfer indicated that
      mClca5 also selectively drives mucous cell metaplasia. Thus, in addition to the
      capacity of CLCA family members to exhibit diverse functional activities, there
      is also preserved function so that more than one family member mediates mucous
      cell metaplasia. Nonetheless, Clca expression appears to be a selective
      determinant of mucous cell metaplasia so that shared homologies between CLCA
      family members may still represent a useful target for focused therapeutic
      intervention in hypersecretory airway disease.

PMID- 16569775
TI  - Heterogeneity of class I INS VNTR allele association with insulin secretion in
      obese children.
AB  - On the basis of the near-complete linkage disequilibrium of the insulin variable
      number of tandem repeats (INS VNTR) allele with the neighboring -23Hph1 A/T
      single-nucleotide polymorphism, previous studies have documented the association
      of class I ("short") and class III ("long") INS VNTR alleles with metabolic
      parameters, including circulating insulin levels. Using a new method to sequence
      class I alleles, we revisited this association in 346 obese children. Class I
      alleles are made of several types of repeats, whose repartition determines
      subclasses IC and ID. Fasting insulin was found to be higher in obese children
      with ID/ID genotypes (135 +/- 12 pmol/l, n = 64) than with ID/IC or IC/IC
      genotypes (91 +/- 5 pmol/l, n = 97, P = 0.0005). In response to oral glucose,
      peak insulin levels and insulin-to-glucose area under the curve ratios were
      higher in ID/ID (872 +/- 122 pmol/l and 109 +/- 15, respectively) than in ID/IC
      or IC/IC patients (586 +/- 42 pmol/l and 76 +/- 5, P = 0.02 and P = 0.04,
      respectively). Fasting and postglucose insulin levels were comparable in carriers
      of IC and of class III alleles. Our results support that the molecular structure
      of the VNTR allele, not only its overall length, is associated with variations of
      insulin secretion. ID/ID homozygosity appears responsible for the increased
      insulin levels previously attributed to the whole class I VNTR group. It will be
      important to test the ramifications of this observation for class I association
      with Type 1 (susceptibility) and Type 2 diabetes (protection).

PMID- 16569776
TI  - Gene expression profiling of target genes in ventilator-induced lung injury.
AB  - In the lungs, high-pressure mechanical ventilation induces an inflammatory
      response similar to that observed in acute respiratory distress syndrome. To
      further characterize these responses and to compare them with classical
      inflammatory pathways, we performed gene expression profiling analysis of 20,000
      mouse genes in isolated blood-free (to exclude genes from sequestered leukocytes)
      perfused mouse lungs exposed to low-pressure ventilation (10 cmH2O), high
      pressure ventilation (25 cmH2O, overventilation), and LPS treatment. A large
      number of inflammatory and apoptotic genes were increased by both overventilation
      and LPS. However, certain growth factor-related genes, as well as genes related
      to development, cellular communication, and the cytoskeleton, were only regulated
      by overventilation. We validated and confirmed increased mRNA expression pattern
      of five genes (amphiregulin, gravin, Nur77, Cyr61, interleukin-11) by real-time
      PCR; furthermore, we confirmed increased protein expression of amphiregulin by
      immunohistochemistry and immunoblotting assays. These genes represent novel
      candidate genes in ventilator-induced lung injury.

PMID- 16569778
TI  - Does hands-on obstetric US experience improve performance on the radiology oral
      board examination?
AB  - PURPOSE: To investigate whether the inclusion of hands-on obstetric
      ultrasonography (US) experience as a formal part of radiology residency affects
      performance on the US section of the oral board examination. MATERIALS AND
      METHODS: An electronic survey was sent to all radiology residency programs to
      assess (a) the time assigned to US rotation, (b) the inclusion of obstetrics in
      US rotation, and (c) the opportunity for hands-on scanning of obstetric patients.
      Blinded results from the 2002 Diagnostic Radiology Oral Board Examination were
      provided by the American Board of Radiology. We recorded the overall examination
      score, US section score, and individual score for all obstetric cases for each
      resident from programs that responded to the survey. A Student t test and
      stratified statistical analyses were performed. This study was determined to be
      exempt from institutional review board approval. Residency directors who
      consented to participate were informed of pertinent information. RESULTS: Of the
      159 programs, 64 (40.3%) responded and 63 (98%) of these had scores available. US
      section scores were provided for 280 residents, with 869 obstetric case scores.
      Fifty (79%) of 63 programs provided the opportunity for hands-on obstetric
      scanning. After adjusting for covariates, there was no significant difference in
      individual resident performance between residents with hands-on scanning
      experience and those without hands-on scanning experience (P = .61). When
      evaluated according to program, there was no significant difference in
      performance between programs with and those without hands-on training (P = .39).
      CONCLUSION: Radiology resident performance in obstetric US on the American Board
      of Radiology Oral Board Examination is similar for programs that provide the
      opportunity for hands-on obstetric scanning compared with those that do not.

PMID- 16569777
TI  - Purine and folate metabolism as a potential target of sex-specific nutrient
      allocation in Drosophila and its implication for lifespan-reproduction tradeoff.
AB  - The reallocation of metabolic resources is important for survival during periods
      of limited nutrient intake. This has an influence on diverse physiological
      processes, including reproduction, repair, and aging. One important aspect of
      resource allocation is the difference between males and females in response to
      nutrient stress. We identified several groups of genes that are regulated in a
      sex-biased manner under complete or protein starvation. These range from expected
      differences in genes involved in reproductive physiology to those involved in
      amino acid utilization, sensory perception, immune response, and growth control.
      A striking difference was observed in purine and the tightly interconnected
      folate metabolism upon protein starvation. From these results, we conclude that
      the purine and folate metabolic pathway is a major point of transcriptional
      regulation during resource allocation and may have relevance for understanding
      the physiological basis for the observed tradeoff between reproduction and
      longevity.

PMID- 16569779
TI  - Screening mammograms: interpretation with computer-aided detection--prospective
      evaluation.
AB  - PURPOSE: To prospectively determine the effect of a commercially available
      computer-aided detection (CAD) system on interpretations of screening mammograms.
      MATERIALS AND METHODS: Institutional review board approval was granted; informed
      consent and HIPAA compliance were waived. A total of 21 349 screening mammograms
      obtained in 18 096 women were interpreted first without and then with review of
      CAD images to determine the effect of CAD analysis on the screening breast cancer
      detection rate, recall rate, and positive predictive value (PPV) for biopsy. The
      percentage of total cancers detected by the radiologists independent of CAD and
      the percentage correctly marked by the CAD system were determined. RESULTS: On
      the basis of pre-CAD interpretations, 2101 patients were recalled for diagnostic
      evaluation, 256 biopsies were performed, and 105 breast cancers were diagnosed.
      The breast cancer detection rate per 1000 screening mammograms was 4.92 (105 of
      21 349 mammograms), the recall rate was 9.84% (2101 of 21 349 mammograms), and
      the PPV for biopsy was 41.0% (105 of 256 biopsies). After CAD image review, 199
      additional patients were recalled, 21 additional biopsies were performed, and
      eight additional cancers were detected. The effect was a 7.62% (eight of 105)
      increase in the number of breast cancers detected, an increase in the recall rate
      to 10.77% (2300 of 21 349 mammograms), and a slight decrease in the PPV to 40.8%
      (113 of 277 biopsies). Radiologists detected 92.9% (105 of 113 cancers) of the
      total cancers, and CAD correctly marked 76.1% (86 of 113 cancers). CONCLUSION:
      The use of CAD improved the detection of breast cancer, with an acceptable
      increase in the recall rate and a minimal increase in the number of biopsies with
      benign results.

PMID- 16569780
TI  - BI-RADS lexicon for US and mammography: interobserver variability and positive
      predictive value.
AB  - PURPOSE: To retrospectively evaluate interobserver variability between breast
      radiologists by using terminology of the fourth edition of the Breast Imaging
      Reporting and Data System (BI-RADS) to categorize lesions on mammograms and
      sonograms and to retrospectively determine the positive predictive value (PPV) of
      BI-RADS categories 4a, 4b, and 4c. MATERIALS AND METHODS: Institutional review
      board approval was obtained; informed consent was not required. This study was
      HIPAA compliant. Ninety-four consecutive lesions in 91 women who underwent image
      guided biopsy comprised 59 masses, 32 calcifications, and three masses with
      calcification. Five radiologists retrospectively reviewed these lesions. Each
      observer described each lesion with BI-RADS terminology and assigned a final BI
      RADS category. Interobserver variability was assessed with the Cohen kappa
      statistic. A pathologic diagnosis was available for all 94 lesions; 30 (32%) were
      malignant and 64 (68%) were benign. Pathologic analysis of benign lesions was
      performed on tissue obtained with image-guided core-needle biopsy. In cases
      referred for excisional biopsy after needle biopsy because of atypia or
      discordance, final surgical pathologic analysis was used for correlation with
      imaging findings. PPV for category 4 or 5 lesions was determined for all readers
      combined. RESULTS: For ultrasonographic (US) descriptors, substantial agreement
      was obtained for lesion orientation, shape, and boundary (kappa = 0.61, 0.66, and
      0.69, respectively). Moderate agreement was obtained for lesion margin and
      posterior acoustic features (kappa = 0.40 for both). Fair agreement was obtained
      for lesion echo pattern (kappa = 0.29). For mammographic descriptors, moderate
      agreement was obtained for mass shape, mass margin, and calcification
      distribution (kappa = 0.48, 0.48, and 0.50, respectively). Fair agreement was
      obtained for calcification description (kappa = 0.32). Slight agreement was
      obtained for mass density (kappa = 0.18). Fair agreement was obtained for final
      assessment category (kappa = 0.28). PPVs of BI-RADS category 4 and 5 assignments
      were as follows: category 4a, six (6%) of 102; category 4b, 17 (15%) of 110;
      category 4c, 48 (53%) of 91; and category 5, 71 (91%) of 78. CONCLUSION:
      Interobserver agreement with the new BI-RADS terminology is good and validates
      the US lexicon. Subcategories 4a, 4b, and 4c are useful in predicting the
      likelihood of malignancy.

PMID- 16569782
TI  - Pulmonary embolism at multi-detector row CT of chest: one-year survival of
      treated and untreated patients.
AB  - PURPOSE: To retrospectively assess outcome in patients with clinically
      unsuspected pulmonary embolism (PE) at chest multi-detector row computed
      tomography (CT). MATERIALS AND METHODS: Institutional review board approval and
      informed consent were not required. PE was assessed in consecutive CT scans in
      1966 patients (mean age, 60 years; range, 15-96 years; male-female ratio, 1.79)
      and graded with severity score. Studies with true-positive and false-negative
      radiologic diagnoses were determined. Coexisting morbidity, anticoagulant therapy
      (ACT), complications, and 1-year outcome were reviewed. Statistical evaluation
      included Mann-Whitney U test, chi(2) test, Poisson regression, and Kaplan-Meier
      statistics. RESULTS: Scans were PE positive in 117 patients. Clinical data review
      was complete in 96 patients; 63 of 96 patients had malignancy; in 58, PE was not
      suspected. In 38 of these 58 patients, radiology report findings were false
      negative (mean severity score, 20.21 +/- 17.88 [standard deviation] and 9.55 +/-
      7.12 for those with true-positive and false-negative findings, respectively; P =
      .012). Forty-nine patients received therapeutic ACT; 21, prophylactic ACT; and
      26, no treatment. PE severity was higher in patients with therapeutic ACT versus
      those without (P < .001). Bleeding complications were more frequent with
      therapeutic ACT (two early deaths, five major nonfatal hemorrhages) than without
      (one minor hemorrhage; P = .037). There were eight early deaths (therapeutic ACT,
      seven; without ACT, one; P = .037). Positive predictors of early death included
      severity score >28, use of systemic thrombolytic therapy, occurrence of major
      hemorrhage, and new-onset cardiac or renal failure (P = .001-.043). Negative
      predictors were report with false-negative findings and no therapeutic ACT (P =
      .007-.037). Predictors of late death (n = 25) were older age, malignancy, and
      renal failure (P = .001-.043). CONCLUSION: Clinically unsuspected PE may remain
      undetected at routine chest CT; these patients have favorable short-term outcome
      without therapeutic ACT.

PMID- 16569781
TI  - Early response of hepatocellular carcinoma to transcatheter arterial
      chemoembolization: choline levels and MR diffusion constants--initial experience.
AB  - PURPOSE: To prospectively investigate the apparent diffusion coefficient (ADC)
      and choline levels measured at hydrogen 1 ((1)H) magnetic resonance (MR)
      spectroscopy, to monitor therapeutic responses of hepatocellular carcinoma (HCC)
      to transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS:
      Institutional review board approval was obtained, and all patients and control
      subjects provided informed consent. Histologically proved large HCCs (>3 cm in
      diameter) were evaluated in 20 patients (16 men and four women; mean age, 59
      years; range, 34-80 years) before TACE and 2-3 days after TACE. A control group
      of eight adults (five men and three women; mean age, 43 years; range, 24-76
      years) with normal livers was examined by using the same protocol. Hepatic
      choline levels were measured by means of an external phantom replacement method,
      quantifying the peak at 3.2 ppm at (1)H MR spectroscopy. ADCs were measured for
      all lesions. A Wilcoxon rank sum test was used to compare absolute choline
      concentrations and ADCs at baseline between HCCs and normal liver parenchyma.
      Changes in choline levels and ADCs in the tumors before and after TACE were
      analyzed by using the Wilcoxon signed rank test. RESULTS: The median preoperative
      choline level in patients with HCC (measured in 18 of the 20 patients) was 4.0
      mmol/L (range, 0.0-17.2 mmol/L), which was significantly higher than that in
      patients with normal livers (n = 8) (median, 1.6 mmol/L; range, 0.0-2.1 mmol/L; P
      < .01). Among 18 patients with HCC, choline levels decreased significantly from
      before TACE to after TACE (P < .01). A significant increase in ADC from before
      TACE to after TACE in the 20 patients with HCC was also found (P < .01).
      CONCLUSION: Hepatic choline levels and ADCs may allow monitoring of therapeutic
      responses of HCC to TACE although larger, more definitive and quantitative
      studies with clinical end points are needed.

PMID- 16569783
TI  - Dynamic MR imaging of breast lesions: correlation with microvessel distribution
      pattern and histologic characteristics of prognosis.
AB  - PURPOSE: To evaluate the association of dynamic enhancement parameters of benign
      and malignant breast lesions at magnetic resonance (MR) imaging with microvessel
      distribution and histologic prognostic tumor characteristics. MATERIALS AND
      METHODS: Regional review board approval and informed consent were obtained.
      Surgical resection specimens of breast lesions (32 benign, 86 malignant) in 118
      patients (age range, 28-86 years; mean, 58 years) who had undergone dynamic T1
      weighted MR imaging of both breasts were included in the study. Different MR
      enhancement parameters and microvessel density (MVD) distribution were
      determined. In malignant lesions, TNM stage, tumor grade, proliferative activity,
      and hormone receptor expression were determined. Spearman correlation
      coefficients; Wilcoxon, Fisher exact, Kruskal Wallis, and chi(2) tests; and
      logistic regression analysis were used for evaluation. RESULTS: Malignant lesions
      exhibited a higher ratio of microvessels in tumor periphery versus tumor center
      than did benign lesions (P < .0005). High vessel ratios (P = .001) and low
      central vessel numbers (P = .007) were associated with high tumor grade. In
      malignant lesions, initial enhancement ratios of periphery to center of lesion
      correlated with the corresponding microvessel ratios (r = 0.61). Yet, a high
      peripheral MVD was not associated with strong peripheral enhancement (r = -0.09).
      High enhancement ratios, washout rates, and early enhancement peaks were
      associated with unfavorable, albeit not significant, prognostic indicators.
      Visible rim enhancement was the most accurate prognostic enhancement criterion
      for estrogen receptor status (P = .007), tumor grade (P = .06), and lymph node
      status (P = .046). Washout was the best discriminating criterion for
      proliferative activity. CONCLUSION: The different enhancement behaviors of
      malignant and benign breast lesions cannot be explained by MVD alone; however, a
      low MVD in the center of carcinoma is reflected quantitatively by a high
      enhancement ratio and qualitatively by rim enhancement, with an implication of
      adverse prognosis.

PMID- 16569784
TI  - Percutaneous drainage of postoperative abdominal abscess with limited
      accessibility: preexisting surgical drains as alternative access route.
AB  - PURPOSE: To retrospectively assess the effectiveness and safety of postoperative
      percutaneous drainage of abdominal abscesses with limited accessibility by using
      a preexisting surgical drain as an access route. MATERIALS AND METHODS: The study
      was approved by the institutional review board, and informed consent was not
      required. The authors reviewed the medical records of 92 patients (62 male, 30
      female; median age, 59 years; age range, 3-79 years) with postoperative abdominal
      abscesses in whom percutaneous drainage was performed by using surgical drains as
      an access. Factors evaluated included the location and size of the lesion; time
      between surgery and the drainage procedure; distance between the lesion and
      surgical drain; presence of fistula; duration of drainage; type of surgical
      drain; size, type, and length of drainage catheter; and complications. Technical
      success was defined as adequate placement of a new drainage catheter into the
      target abscess. Midterm success was defined as avoidance of surgery or additional
      percutaneous drainage during the 6 months of follow-up. Univariate analysis and
      multiple logistic regression analysis were performed to determine factors that
      affected the technical or midterm success of the procedure. RESULTS: Of 92
      postoperative abscesses for which the technique was attempted, 56 (61%) had a
      subphrenic location and 36 (39%) had a peripancreatic location. Technical success
      was achieved in 87 of the 92 patients (95%). Technical success was not
      significantly associated with any of the factors tested. Midterm success was
      achieved in 75 of the 87 patients (86%) in whom technical success was achieved.
      Midterm failure showed a statistically significant relationship with the presence
      of fistula (P = .04). No procedure-related complications were identified.
      CONCLUSION: Percutaneous drainage by using the surgical drain as an access route
      is an effective and safe alternative for draining postoperative abdominal
      abscesses that are less accessible with direct puncture..

PMID- 16569785
TI  - Radiosensitive functional dye: clinical application for estimation of patient
      skin dose.
AB  - Institutional review board approval and informed patient consent were obtained.
      The purpose of the study was to prospectively evaluate the use of radiosensitive
      indicators to estimate patient entrance skin dose (ESD). Forty-six patients wore
      a jacket with 48 or 52 indicators adhered to the back during percutaneous
      coronary interventions; they had eight additional indicators on their upper arms.
      The patients' ESDs were calculated according to the change in color of the
      indicators. There were good correlations between the ESDs estimated by using
      color measurements performed with an optical instrument and those estimated at
      visual observation (P < .001) and between the ESDs estimated by using a
      thermoluminescent dosimeter and those estimated by using color measurements (P <
      .001). The radiosensitive indicator method seems to be useful for estimating ESDs
      and their distribution during percutaneous coronary intervention; however, visual
      observation is reliable for estimating doses of up to 5 Gy only. (c) RSNA, 2006.

PMID- 16569786
TI  - Trabecular bone structure of the calcaneus: comparison of MR imaging at 3.0 and
      1.5 T with micro-CT as the standard of reference.
AB  - PURPOSE: To investigate in vitro the calcaneal trabecular bone structure in
      elderly human donors with high spatial resolution magnetic resonance (MR) imaging
      at 3.0 T and 1.5 T, to quantitatively compare MR measures of bone
      microarchitecture with those from micro-computed tomography (CT), and to compare
      the performance of 3.0-T MR imaging with that of 1.5-T MR imaging in
      differentiating donors with spinal fractures from those without spinal fractures.
      MATERIALS AND METHODS: The study was performed in line with institutional and
      legislative requirements; all donors had dedicated their body for educational and
      research purposes prior to death. Sagittal MR images of 49 human calcaneus
      cadaveric specimens were obtained (mean age of donors, 79.5 years +/- 11
      [standard deviation]; 26 male donors, 23 female donors). After the spatial
      coregistering of images acquired at 3.0-T and 1.5-T MR imaging, the signal-to
      noise-ratios and structural parameters obtained at each magnetic field strength
      were compared in corresponding sections. Micro-CT was performed on calcaneus
      cores obtained from corresponding regions in 40 cadaveric specimens. Vertebral
      deformities of the thoracic and lumbar spine were radiographically classified by
      using the spinal fracture index. Diagnostic performance of the structural
      parameters in differentiating donors with vertebral fractures from those without
      was assessed by using receiver operator characteristic (ROC) analysis, including
      area under the ROC curve (A(z)). RESULTS: Correlations between structural
      parameters at 3.0-T MR imaging and those at micro-CT were significantly higher (P
      < .05) than correlations between structural parameters at 1.5-T MR imaging and
      those at micro-CT (trabecular thickness, r = 0.76 at 3.0 T vs r = 0.57 at 1.5 T).
      Trabecular dimensions were amplified at 3.0 T because of increasing
      susceptibility artifacts. Also, higher ROC values were found for structural
      parameters at 3.0 T than at 1.5 T, but differences were not significant
      (trabecular thickness, A(z) = 0.75 at 3.0 T vs A(z) = 0.66 at 1.5 T, P > .05).
      CONCLUSION: MR imaging at 3.0 T provided a better measure of the trabecular bone
      structure than did MR imaging at 1.5 T. There was a trend for better
      differentiation of donors with from those without osteoporotic vertebral
      fractures at 3.0 T than at 1.5 T.

PMID- 16569787
TI  - Computer-aided detection of breast cancer: a cost-effectiveness study.
AB  - PURPOSE: To analyze the cost-effectiveness of adding computer-aided detection
      (CAD) to a screening mammography program. MATERIALS AND METHODS: A Markov model
      was developed to compare three hypothetical groups of women aged 40-79 years. The
      first group was composed of women undergoing mammographic screening without CAD;
      the second, of women undergoing mammographic screening with CAD; and the third,
      of women undergoing observation without screening. Cost-effectiveness was
      expressed as the marginal cost per year of life saved (MCYLS). MCYLS was
      calculated for screening mammography with CAD compared with screening mammography
      alone and for screening mammography alone compared with observation. Sensitivity
      analyses were performed by varying the cost of CAD, the rates of cancer detection
      with CAD, and the stage distribution of breast cancers diagnosed with CAD.
      RESULTS: Adding CAD to a mammographic screening program resulted in a MCYLS of
      $19,058. The MCYLS of screening mammography alone compared with observation was
      $16,023. CAD increases the marginal effectiveness of screening by 29%; however,
      the marginal cost of screening is also increased by 34%. Varying the cost of CAD
      yields a linear increase in MCYLS from $8937 with CAD at $9 per case to $24,924
      with CAD at $25 per case. The cost-effectiveness of CAD is dependent on the
      magnitude of the increase in cancer detection rates with CAD but is also affected
      by the stage distribution of cancers diagnosed with CAD. CONCLUSION: The MCYLS is
      19% greater for CAD added to screening versus screening mammography alone but is
      still within the accepted range for cost-effectiveness.

PMID- 16569788
TI  - Transition zone prostate cancers: features, detection, localization, and staging
      at endorectal MR imaging.
AB  - PURPOSE: To retrospectively evaluate the accuracy of endorectal magnetic
      resonance (MR) imaging in the detection and local staging of transition zone
      prostate cancers, with pathologic analysis serving as the reference standard, and
      to assess MR imaging features of these cancers. MATERIALS AND METHODS: The
      institutional review board approved this HIPAA-compliant retrospective study and
      waived the informed consent requirement. An institutional database of 986
      patients who underwent MR imaging before radical prostatectomy yielded 148
      consecutive patients with at least one transition zone cancer at step-section
      pathologic analysis. An additional 46 patients without transition zone cancer
      were randomly selected as a control group. Two readers independently reviewed MR
      studies to identify patients with transition zone cancers and determine the
      location and local extent of these cancers. Imaging features that helped in the
      identification of transition zone cancers were recorded. Descriptive and kappa
      statistics, as well as receiver operating characteristic and multivariate
      logistic regression analyses, were used. RESULTS: For identification of patients
      with transition zone cancers, sensitivity and specificity were 75% and 87%,
      respectively, for reader 1 and 80% and 78%, respectively, for reader 2.
      Interreader agreement was fair. For detection of the location of transition zone
      cancer, the area under the receiver operating characteristic curve was 0.75 for
      reader 1 and 0.73 for reader 2. Interreader agreement was fair. The readers'
      accuracy in detecting transition zone cancer foci increased significantly
      (P=.001) as tumor volume increased. In the detection of extraprostatic extension
      of transition zone cancers, sensitivity and specificity were 56% and 94%,
      respectively, for reader 1 and 28% and 93%, respectively, for reader 2.
      Homogeneous low T2 signal intensity (P=.001 for reader 1, P<.001 for reader 2)
      and lenticular shape (P=.017 for reader 1) were significantly associated with the
      presence of transition zone cancer. CONCLUSION: MR imaging can be used to detect,
      localize, and stage transition zone prostate cancers.

PMID- 16569789
TI  - Potentially serious adverse events at CT colonography in symptomatic patients:
      national survey of the United Kingdom.
AB  - PURPOSE: To retrospectively determine the incidence of potentially serious
      adverse events associated with computed tomographic (CT) colonography performed
      in patients with symptoms of colorectal cancer. MATERIALS AND METHODS: Ethical
      approval and informed consent were waived, since the study was deemed a clinical
      audit and patients would not be approached. With a national survey in the United
      Kingdom, all departments offering CT colonography in everyday practice were
      identified. The lead gastrointestinal radiologist from all responding departments
      was interviewed, and the frequency of potentially serious adverse events
      associated with CT colonography performed in patients with symptoms of colorectal
      cancer, the total number of examinations performed, and technical factors
      possibly related to perforation were determined. Where a potentially serious
      adverse event was encountered, it was explored in detail. Responses were
      collated, and raw frequencies were determined. Fisher exact test was used to
      determine differences in event rates between groups. RESULTS: At 50 centers, 17
      067 CT colonographic examinations (mean number per center, 359; range, 10-3000)
      were performed. No deaths were reported. Thirteen patients (one [0.08%] of 1313)
      had had a potentially serious adverse event related to the procedure. There were
      nine perforations: Four (44%) were asymptomatic and five (56%) were symptomatic,
      and perforation had an attributable cause, with a symptomatic perforation rate of
      0.03% (one in 3413 patients). One patient required laparotomy. An inflated rectal
      balloon was used to perform 9378 examinations. There was no significant
      difference between the proportion of perforations associated with rectal balloon
      inflation (n = 6) and the proportion of those that were not (n = 2) (P = .3).
      CONCLUSION: Potentially serious adverse events related to CT colonography
      occurred in 0.08% of symptomatic patients.

PMID- 16569790
TI  - Recommendation to develop strategies to increase the number of ST-segment
      elevation myocardial infarction patients with timely access to primary
      percutaneous coronary intervention.
AB  - Although evidence suggests that primary percutaneous coronary intervention (PCI)
      is the preferred reperfusion strategy in the majority of patients with ST-segment
      elevation myocardial infarction (STEMI), only a minority of patients with STEMI
      are treated with primary PCI, and of those, only a minority receive the treatment
      within the recommended 90 minutes after entry into the medical system. Market
      research conducted by the American Heart Association revealed that those involved
      in the care of patients with STEMI recognize the multiple barriers that prevent
      the prompt delivery of primary PCI and agree that it is necessary to develop
      systems or centers of care that will allow STEMI patients to benefit from primary
      PCI. The American Heart Association will convene a group of stakeholders
      (representing the interests of patients, physicians, emergency medical systems,
      community hospitals, tertiary hospitals, and payers) and quality-of-care and
      outcomes experts to identify the gaps between the existing and ideal delivery of
      care for STEMI patients, as well as the requisite policy implications. Working
      within a framework of guiding principles, the group will recommend strategies to
      increase the number of STEMI patients with timely access to primary PCI.

PMID- 16569791
TI  - Atypical antipsychotic-induced akathisia with depression: therapeutic role of
      mirtazapine.
AB  - OBJECTIVE: To investigate the efficacy of mirtazapine in treating akathisia
      caused by risperidone and olanzapine, as well as its use in alleviating comorbid
      depressive disorder. CASE SUMMARIES: Five patients with diagnoses varying from
      schizophrenia, delusional disorder, and bipolar disorder developed akathisia
      while on treatment with olanzapine and risperidone. The likelihood that
      risperidone and olanzapine had induced akathisia in all patients was rated
      probable according to the Naranjo probability scale. Four of these patients were
      also found to be depressed. The akathisia was successfully treated with
      mirtazapine, and 3 of the 4 depressed patients improved with mirtazapine
      treatment. Use of mirtazapine did not result in any adverse effect. DISCUSSION:
      Mirtazapine is a potent antagonist of central alpha(2) auto- and hetero
      adrenergic receptors, as well as an antagonist of 5-HT(2A/2C), 5-HT(3), and
      histaminergic H(1) postsynaptic receptors. The efficacy of mirtazapine in
      treatment of akathisia may result from its antagonist property at the H(1)
      receptors and its dopaminergic activity in frontal cortex. The use of mirtazapine
      offers advantages over other anti-akathisia drugs in its better adverse effect
      profile, as well as its ability to treat coexisting depression. CONCLUSIONS:
      Mirtazapine is efficacious in treating atypical antipsychotic-induced akathisia.
      It may be a good option, particularly in patients with coexisting depression.

PMID- 16569792
TI  - Implementation of ward-based clinical pharmacy services in Belgium--description
      of the impact on a geriatric unit.
AB  - BACKGROUND: Patient-centered clinical pharmacy services are still poorly
      developed in Europe, despite their demonstrated advantages in North America and
      the UK. Reporting European pilot experiences is, therefore, important to assess
      the usefulness of clinical pharmacy services in this specific context. OBJECTIVE:
      To report the results of the first implementation of Belgian clinical pharmacy
      services targeting patients at high risk of drug-related problems. METHODS: An
      intervention study was conducted by a trained clinical pharmacist providing
      pharmaceutical care to 101 patients (mean age 82.2 y; mean +/- SD number of
      prescribed drugs 7.8 +/- 3.5) admitted to an acute geriatric unit, over a 7 month
      period. All interventions to optimize prescribing, and their acceptance, were
      recorded. An external panel (2 geriatricians, 1 clinical pharmacist) assessed the
      interventions' clinical significance. Persistence of interventions after
      discharge was assessed through telephone calls. RESULTS: A total of 1066
      interventions were made over the 7 month period. The most frequent drug-related
      problems underlying interventions were: underuse (15.9%), wrong dose (11.9%),
      inappropriate duration of therapy (9.7%), and inappropriate choice of medicine
      (9.6%). The most prevalent consequences were to discontinue a drug (24.5%), add a
      drug (18.6%), and change dosage (13.7%). Acceptance rate by physicians was 87.8%.
      Among interventions with clinical impact, 68.3% and 28.6% had moderate and major
      clinical significance, respectively. Persistence of chronic treatment changes 3
      months after discharge was 84%. CONCLUSIONS: Involving a trained clinical
      pharmacist in a geriatric team led to clinically relevant and well-accepted
      optimization of medicine use. This initiative may be a springboard for further
      development of clinical pharmacy services.

PMID- 16569793
TI  - Diabetic patient compliance as a function of counseling. 1979.
AB  - The impact of a specially designed patient education program upon the diabetes
      related knowledge and compliance of insulin dependent diabetic patients was
      investigated. The program consisted of an audiovisual presentation, illustrated
      handout material, and pharmacist-patient counseling. Based on statistical
      considerations, 65 eligible patients were assigned systematically to a control
      group (Group I) and a study group (Group II) and were evaluated for compliance
      following a standardized protocol. Immediately following the interview, Group II
      patients were instructed utilizing the patient education program. Scores for
      initial and final evaluations of knowledge and compliance were compared using
      appropriate statistical procedures. The program was successful in producing
      improvements in both knowledge and compliance but a need for individualization of
      patient education efforts was indicated. Significant improvements in compliance
      were not observed among patients older than the mean age for study patients and
      those with diabetes complicated by cardiovascular and hypertensive disease.

PMID- 16569794
TI  - The value of emergency care situations in the clinical pharmacy education of a
      pharmacist. 1974.

PMID- 16569795
TI  - Critical care therapeutics: a frontier for clinical pharmacy. 1982.

PMID- 16569797
TI  - Comparative absorption profiles of divalproex sodium delayed-release versus
      extended-release tablets -- clinical implications.
AB  - BACKGROUND: The distinct absorption characteristics of the conventional enteric
      coated, delayed-release (DR) and the novel extended-release (ER) divalproex
      sodium formulations are not well recognized. OBJECTIVE: To quantitatively and
      qualitatively differentiate the absorption characteristics of divalproex-DR and 
      ER formulations. METHODS: Healthy volunteers (N = 28) received single 1000 mg
      doses of divalproex-DR and divalproex-ER tablets in a crossover fashion.
      Noncompartmental and compartmental analyses were used to estimate valproic acid
      (VPA) pharmacokinetics from the plasma concentration-time profiles determined
      from intensive blood sampling over 48 hours. RESULTS: VPA was not absorbed from
      divalproex-DR in the first 2 hours (absorption lag-time) after dosing. After VPA
      release in the intestine, approximately 63% of the dose was absorbed in less than
      1 hour, that is, 2.9 hours (mean absorption time) from dosing. Maximum
      concentration (C(max)) was achieved approximately 4 hours after dosing. VPA
      absorption was complete ( approximately 93% of dose) within 3 absorption half
      lives ( approximately 4.5 h) post-absorption lag-time, that is, 6-7 hours from
      dosing. In contrast, VPA absorption from divalproex-ER starts immediately after
      administration, initially at a modest rate, followed by slow and extended
      absorption at a constant rate for more than 20 hours; VPA concentrations at 1 and
      2 hours were 28% and 40% of C(max). Approximately 53% of the dose was absorbed
      within 12 hours (mean absorption time); complete absorption occurred over more
      than 20 hours without any dose dumping. CONCLUSIONS: VPA absorption from enteric
      coated divalproex-DR is rapid following a lag-time of approximately 2 hours and
      is complete within 6-7 hours of dosing. In contrast, VPA absorption from
      divalproex-ER starts immediately after administration, but occurs at a slow,
      approximately constant rate over more than 20 hours.

PMID- 16569798
TI  - Pharmaceutical care in community pharmacies: practice and research in Germany.
AB  - OBJECTIVE: To discuss the provision of pharmaceutical care in community
      pharmacies in Germany including community pharmacy, organization and delivery of
      health services, pharmacy education, community pharmacy services, research in
      community pharmacy, and future plans for community pharmacy services. FINDINGS:
      In Germany, cognitive pharmaceutical services have been developed for more than
      12 years. Several studies and programs have shown that pharmaceutical care and
      other pharmaceutical services are feasible in community pharmacy practice and
      that patients benefit from these services. In 2003, a nationwide contract was
      established between representatives of the community pharmacy owners and the
      largest German health insurance fund. In this so-called family pharmacy contract,
      remuneration of pharmacists for provision of pharmaceutical care services was
      successfully negotiated for the first time. In 2004, a trilateral integrated care
      contract was signed that additionally included general practitioners, combining
      the family pharmacy with the family physician. Within a few months, the vast
      majority (>17 000) of community pharmacies have registered to participate in this
      program. CONCLUSIONS: German community pharmacies are moving from the image of
      mainly supplying drugs toward the provision of cognitive pharmaceutical services.

PMID- 16569799
TI  - Cost-utility model of rasagiline in the treatment of advanced Parkinson's disease
      in Finland.
AB  - BACKGROUND: The economic burden of Parkinson's disease (PD) is high, especially
      in patients experiencing motor fluctuations. Rasagiline has demonstrated efficacy
      against symptoms of PD in early and advanced stages of the disease. OBJECTIVE: To
      assess the cost-utility of rasagiline and entacapone as adjunctive therapies to
      levodopa versus standard levodopa care in PD patients with motor fluctuations in
      Finland. METHODS: A 2 year probabilistic Markov model with 3 health states: "25%
      or less off-time/day," "greater than 25% off-time/day," and "dead" was used. Off
      time represents time awake with poor or absent motor function. Model inputs
      included transition probabilities from randomized clinical trials, utilities from
      a preference measurement study, and costs and resources from a Finnish cost-of
      illness study. Effectiveness measures were quality-adjusted life years (QALYs)
      and number of months spent with 25% or less off-time/day. Uncertainty around
      parameters was taken into account by Monte Carlo simulations. RESULTS: Over 2
      years from a societal perspective, rasagiline or entacapone as adjunctive
      therapies to levodopa showed greater effectiveness than levodopa alone at no
      additional costs. Benefits after 2 years were 0.13 (95% CI 0.08 to 0.17)
      additional QALYs and 5.2 (3.6 to 6.7) additional months for rasagiline and 0.12
      (0.08 to 0.17) QALYs and 5.1 (3.5 to 6.6) months for entacapone, both in adjunct
      to levodopa compared with levodopa alone. CONCLUSIONS: The results of this study
      support the use of rasagiline and entacapone as adjunctive cost-effective
      alternatives to levodopa alone in PD patients with motor fluctuations in Finland.
      With a different mode of action, rasagiline is a valuable therapeutic alternative
      to entacapone at no additional charge to society.

PMID- 16569800
TI  - Acute dystonia with low-dosage aripiprazole in Tourette's disorder.
AB  - OBJECTIVE: To report a case of an acute dystonic episode in a patient with
      Tourette's disorder (TD) treated with the partial dopamine agonist aripiprazole.
      CASE SUMMARY: An 18-year-old male with TD was prescribed aripiprazole 10 mg
      orally daily, which produced a significant improvement in his symptoms. However,
      after 3 days of treatment, he experienced an acute episode of dystonia with
      facial muscle spasm, oculogyric crisis, and torticolis. All symptoms resolved
      after a single intramuscular injection of biperidine 5 mg. The Naranjo
      probability scale indicated that the adverse events were probably caused by
      aripiprazole. DISCUSSION: To our knowledge, as of this writing, this is the first
      report concerning an aripiprazole-induced dystonic episode in an adult, and it is
      especially notable because it occurred at low dosage. Aripiprazole is a dopamine
      partial agonist and a serotonin(2A) antagonist with a favorable adverse effect
      profile. Short-term clinical trials reported a very low incidence of
      extrapyramidal symptoms, with akathisia being the most common, although there
      have been reports of severe extrapyramidal symptoms in a 3-year-old child and in
      an adolescent with a previous history of such symptoms. CONCLUSIONS: Acute
      dystonic phenomena may be caused by aripiprazole, although the drug's suggested
      mode of action largely precludes them.

PMID- 16569801
TI  - Recent advances in neonatal pharmacotherapy.
AB  - OBJECTIVE: To provide commentary and reviews and brief discussions in
      controversial or innovative recent advances in neonatal pharmacotherapy. To
      discuss cutting edge drug delivery systems that may become useful in neonatal
      drug delivery in the future. DATA SOURCES: Articles were identified through
      searches of MEDLINE (1990-October 2005), key articles in the authors' files, and
      in some cases, through data generated and/or published by the author of a
      particular topic. DATA SELECTION: Article selection and relevance to the topics
      under discussion was determined by individual authors. DATA SYNTHESIS:
      Therapeutic strategies addressed in this review include the use of hematopoietic
      growth factors including a simulated amniotic fluid preparation containing these
      growth factors for neonates with selected gastrointestinal problems,
      erythropoietin for neuroprotection following perinatal asphyxia, drug therapy
      advances in treatment of patent ductus arteriosus (PDA), evaluation of advances
      in transdermal drug delivery, and its potential application to neonates and
      advances in the treatment of persistent pulmonary hypertension (PPHN) of the
      newborn. CONCLUSIONS: Despite being over 30 years old, the practice of
      neonatology is as much of an art as a science. Advances in the basic science
      research have improved our understanding of use of pharmacologic agents in the
      premature and full-term neonate including drug disposition pathways. Expanding
      our knowledge on issues such as physiology of hematopoietic factors, the
      pharmacologic responses of conditions such as PDA and PPHN, and newer
      technologies for drug administration, as well as other pharmacologic responses in
      the neonate are vital in the development of safe and efficacious treatments for
      neonates. Many questions remain unanswered, and every clinician must make an
      effort to contribute to the knowledge and understanding of pharmacotherapy in
      this patient population.

PMID- 16569802
TI  - Naturalistic impact of second-generation antipsychotics on weight gain.
AB  - BACKGROUND: While second-generation antipsychotics (SGAs) have had benefits over
      earlier antipsychotic treatments, their use has been associated with reports of
      weight gain. Body mass index (BMI) has been studied in clinical trials with
      limited comparison between drugs. OBJECTIVE: To investigate the impact of each
      SGA on the risk of weight increase in an adult population. METHODS: Using a
      national electronic medical records database, a naturalistic impact of SGAs on
      BMI was evaluated. Patients (aged >/=18 y) receiving a prescription for an
      antipsychotic drug between January 1995 and March 2004 were identified. An
      adverse event was defined as at least a 7% increase in BMI from baseline within
      one year of antipsychotic prescription and a post-increase BMI of at least 25
      kg/m(2). RESULTS: A total of 9394 patients were identified, with 1514 cases of
      increased BMI after initial prescription. Risperidone (OR 1.39; 95% CI 1.16 to
      1.66), quetiapine (OR 1.36; 95% CI 1.13 to 1.64), and olanzapine (OR 1.76; 95% CI
      1.50 to 2.07) were significantly more likely to cause BMI increase compared with
      first-generation antipsychotics (FGAs). Aripiprazole (OR 0.72; 95% CI 0.36 to
      1.46), ziprasidone (OR 0.68; 95% CI 0.39 to 1.18), and clozapine (OR 1.01; 95% CI
      0.56 to 1.81) were less likely to induce weight gain compared with FGAs.
      CONCLUSIONS: This study provides a foundation for understanding how SGAs impact
      weight gain in a naturalistic, as opposed to a clinical trial, setting and
      provides evidence that there are differential risks of weight gain between SGAs.
      Because of negative long-term health effects of weight gain, physicians need to
      take all factors into consideration when recommending pharmaceutical therapy for
      patients with severe mental illness.

PMID- 16569803
TI  - Critical care pharmacy services in United States hospitals.
AB  - BACKGROUND: Critical care pharmacy activities have been described as fundamental,
      desirable, and optimal, but actual services provided have not been evaluated.
      OBJECTIVE: To characterize the type and level of pharmacy services provided to
      intensive care units (ICUs). METHODS: A 38 question survey was sent in 2
      consecutive mailings to all US institutions (N = 3238) with an ICU. Questions
      were categorized according to clinical, educational, administrative, and
      scholarly activities, with levels of services stratified as fundamental,
      desirable, or optimal. RESULTS: Completed surveys were received from 382 (11.8%)
      institutions encompassing 1034 ICUs. Direct clinical pharmacy activities were
      provided at 62.2% of ICUs. The pharmacists in those programs attended rounds 4.4
      +/- 1.5 days/wk, mean +/- SD, and had a workweek that consisted of patient care
      (43% of hours worked), drug distribution (26.2%), administration (12.6%),
      education (10.9%), and scholarly activities (7.3%). Fundamental clinical
      activities performed during at least 75% of patient ICU days were providing drug
      information, drug therapy evaluation, drug therapy intervention, and
      pharmacokinetic monitoring. Conducting in-services (92.8%), a fundamental
      service, was the only educational activity frequently provided. Most respondents
      were involved with at least one multidisciplinary committee, and 45.5% conducted
      scholarly activities. Desirable or optimal activities were not frequently
      provided across all service categories. CONCLUSIONS: Clinical pharmacists are
      directly involved as caregivers in nearly two-thirds of ICUs in the US. Although
      they provide a range of clinical and administrative services, involvement in
      educational and scholarly activities is variable. The level of services provided
      is consistent with the criteria deemed fundamental for improving patient care.
      Higher-order services are far less likely to be provided.

PMID- 16569804
TI  - Dutasteride: a dual 5-alpha reductase inhibitor for the treatment of symptomatic
      benign prostatic hyperplasia.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, drug
      interactions, and dosing recommendations of dutasteride, a 5-alpha reductase
      inhibitor for benign prostatic hyperplasia (BPH). DATA SOURCES: A MEDLINE search
      (1966-February 2006) was conducted to extract human research data in the English
      language on dutasteride. Search terms included benign prostatic hyperplasia,
      dutasteride, and finasteride. The reference lists of articles identified through
      this search process, the manufacturer's Web site, and dutasteride prescribing
      information were also examined. STUDY SELECTION AND DATA EXTRACTION: All
      published studies and clinical data from the manufacturer were included, with
      emphasis placed on randomized, controlled trials. DATA SYNTHESIS: Dutasteride is
      approved for the treatment of symptomatic BPH in men with an enlarged prostate to
      improve urinary symptoms, reduce the risk of acute urinary retention, and reduce
      the need for BPH-related surgical interventions. Compared with placebo,
      dutasteride has been shown to significantly improve BPH symptoms, reduce the
      incidence of acute urinary retention and BPH-related surgery, and improve BPH
      related quality of life. Few published data exist comparing dutasteride with
      finasteride. The most common adverse effects of dutasteride include ear, nose,
      and throat infection; malaise; headache; dizziness; and musculoskeletal pain.
      CONCLUSIONS: Clinical trials, sponsored primarily by the manufacturer, have shown
      dutasteride to be an effective treatment of BPH compared with placebo and to
      likely possess efficacy similar to that of finasteride. Further studies are
      needed to gain a more clear understanding of any clinically significant
      differences between dutasteride and finasteride.

PMID- 16569806
TI  - Comment: analysis of severe adverse events related to the use of mifepristone as
      an abortifacient.

PMID- 16569807
TI  - Depressive symptoms in coronary artery disease patients after hypertension
      treatment.
AB  - BACKGROUND: Depression is highly prevalent and frequently recurs in patients with
      coronary artery disease (CAD) and hypertension. Certain medications used to treat
      hypertension are alleged to be associated with higher risk of depression.
      OBJECTIVE: To compare depressive symptoms before and during treatment with 2
      equivalent hypertension treatment strategies in patients with CAD stratified
      according to a self-reported history of physician-diagnosed depression. METHODS:
      Patients enrolled in a randomized hypertension treatment study were mailed
      baseline and one year follow-up surveys and stratified according to a self
      reported history of depression. Patients (N = 1152) were 50 years old or older
      with hypertension and clinically stable CAD. Depressive symptoms were measured
      using the Center for Epidemiologic Studies-Depression (CES-D). High risk of
      depression was defined as a history of physician-diagnosed depression reported by
      patients on the baseline survey. Depressive symptoms were compared for verapamil
      sustained-release (SR)- and atenolol-based hypertension treatment. RESULTS: Among
      patients with a previous history of depression, depressive symptoms improved over
      the one year follow-up period for patients assigned to both treatment regimens.
      Depressive symptoms improved for patients with no depression history in the
      verapamil SR group (p < 0.001) and were unchanged in the atenolol group (p =
      0.52). Patients assigned to the atenolol-based strategy without prior history of
      depression were more likely to worsen 5 or more points on the CES-D. CONCLUSIONS:
      When antihypertensive treatment options are clinically equivalent, prescribers
      may first consider using a verapamil SR-based strategy, especially in patients
      with CAD who have no history of depression.

PMID- 16569808
TI  - Aminoglycoside elimination in extended duration hemodialysis.

PMID- 16569809
TI  - Critical care.
AB  - 2006 marks the 40th year of publication for The Annals. Over that time, The
      Annals has been an important contributor to the development of clinical pharmacy.
      Throughout 2006, we are publishing articles reflecting on the history of clinical
      pharmacy through the eyes of practitioners, including those pioneering clinical
      pharmacy, as well as those who have more recently entered the profession and a
      well-established specialty.

PMID- 16569810
TI  - Pantoprazole-induced thrombocytopenia.
AB  - OBJECTIVE: To report 2 cases of thrombocytopenia associated with pantoprazole
      treatment and discuss existing reports on this drug-induced adverse event. CASE
      SUMMARIES: This paper describes the course of thrombocytopenia associated with
      pantoprazole 40 mg in 2 hospitalized patients. In both cases, thrombocytopenia
      appeared after the initiation of pantoprazole and rapidly improved after
      discontinuation of pantoprazole, although complete resolution of thrombocytopenia
      occurred in only one patient prior to discharge from the hospital. DISCUSSION:
      The mechanism of drug-induced thrombocytopenia is often poorly understood, and
      proton-pump inhibitors are generally not strongly suspected as a cause of
      thrombocytopenia. However, an objective causality assessment using the Naranjo
      probability scale revealed a probable relationship between thrombocytopenia and
      pantoprazole in both of the cases. It is unknown whether this is a class effect.
      CONCLUSIONS: Although drug-induced thrombocytopenia with pantoprazole appears to
      be rare, it represents a potentially severe adverse effect. This supports the
      judicious prescribing of pantoprazole and possibly other proton-pump inhibitors.

PMID- 16569811
TI  - Risperidone treatment of bipolar mania.
AB  - OBJECTIVE: To review clinical trial evidence regarding the efficacy and safety of
      risperidone for the treatment of bipolar mania. DATA SOURCES: Articles were
      identified through searches of PubMed (1950-August 2005), EMBASE (1988-August
      2005 week 37), and International Pharmaceutical Abstracts (1970-August 2005)
      databases using the key words risperidone, atypical antipsychotics, and bipolar
      mania. Additional references were found through review of bibliographies of
      identified articles. PubMed searches for efficacy and safety were limited to
      clinical trials. STUDY SELECTION AND DATA EXTRACTION: Six randomized trials and 6
      observational studies of risperidone monotherapy or combination therapy for
      bipolar mania in adults were selected. DATA SYNTHESIS: Randomized, placebo
      controlled and observational trials reported that risperidone monotherapy
      decreases manic symptoms in patients with a moderate severity of mania, as
      determined by change in Young Mania Rating Scale (YMRS) scores. Adverse effects
      observed in monotherapy trials included somnolence, extrapyramidal symptoms
      (EPS), and weight gain. Clinical trials of risperidone in combination with other
      mood stabilizers (ie, lithium, valproate, carbamazepine, topiramate) also
      reported decreases in YMRS scores in patients with moderate and severe manic
      symptoms. CONCLUSIONS: Risperidone monotherapy or adjunctive therapy with other
      first-line mood stabilizers may be effective for the treatment of acute bipolar
      mania in adults with moderate severity of mania. The use of risperidone as
      monotherapy in severe mania or in maintenance treatment remains to be elucidated.

PMID- 16569812
TI  - Outcomes of a lipid management program in a rural nurse practitioner clinic.

PMID- 16569813
TI  - Argatroban dosing of patients with heparin-induced thrombocytopenia and an
      elevated aPTT due to antiphospholipid antibody syndrome.
AB  - OBJECTIVE: To describe the clinical characteristics, management, and outcomes of
      patients with heparin-induced thrombocytopenia with thrombosis (HITTS) or without
      thrombosis (HIT) who also had an elevated baseline activated partial
      thromboplastin time (aPTT) due to antiphospholipid antibody syndrome (APS). CASE
      SUMMARY: Four patients with HIT/HITTS and an elevated baseline aPTT due to APS
      were identified. Two patients had venous thrombosis, 1 had limb ischemia, and 1
      had isolated HIT. All 4 were managed with a weight-based fixed dose of argatroban
      without laboratory monitoring. None of the patients had thrombotic or bleeding
      complications once therapy was initiated. DISCUSSION: Management of patients with
      HIT/HITTS and an abnormal baseline aPTT due to APS is problematic. We review
      alternative management strategies, such as monitoring direct thrombin inhibitors
      with the ecarin clotting time or thrombin inhibition time or using an alternative
      anticoagulant, such as fondaparinux. As of March 13, 2006, none of these
      management strategies has been evaluated in a clinical trial for this patient
      population. We report the successful use of weight-based, fixed-dose argatroban
      without laboratory monitoring in patients with APS. CONCLUSIONS: Use of a fixed
      dose argatroban regimen without laboratory monitoring is a potential management
      strategy for patients with HIT/HITTS and an elevated baseline aPTT due to APS.

PMID- 16569814
TI  - Safety of Angiotensin-converting enzyme inhibitors in patients with insect venom
      allergies.
AB  - OBJECTIVE: To review the literature with respect to the safety of angiotensin
      converting enzyme (ACE) inhibitors in patients allergic to insect venom and those
      undergoing venom immunotherapy (VIT). DATA SOURCES: A MEDLINE search was
      conducted (1966-March 2006) using the following search terms: bee sting, venom,
      insect stings, ACE inhibitors, angiotensin II receptor blockers, immunotherapy,
      and desensitization. The bibliographies of qualifying articles were also searched
      for relevant references. DATA SYNTHESIS: Several case reports have described
      severe allergic reactions, including anaphylaxis, in patients taking ACE
      inhibitors subsequent to being stung or receiving VIT. Exacerbation of the
      allergic response by ACE inhibitors is thought to be related to accumulation of
      bradykinin and inhibition of the formation of angiotensin II. Similar reactions
      have not been described with angiotensin-receptor blockers, but are theoretically
      possible. CONCLUSIONS: ACE inhibitors may exacerbate the response to insect
      venom, resulting in potentially life-threatening allergic reactions to insect
      stings or VIT. Although this risk is difficult to quantify based only on data
      from case reports, it seems prudent that patients with documented allergic
      reactions to insect venom avoid ACE inhibitor therapy, if possible. If, after
      careful consideration of the risks and benefits, ACE inhibitor therapy is deemed
      warranted, education regarding measures to minimize exposure to insect stings and
      training on self-administration of epinephrine should be provided, as with any
      person with venom allergy. In patients in whom VIT is appropriate, temporary
      discontinuation of the ACE inhibitor prior to each venom injection may prevent
      subsequent adverse reactions.

PMID- 16569815
TI  - Development and validation of the medication-based disease burden index.
AB  - BACKGROUND: Medication lists offer an alternative source of data on comorbidities
      and disease burden. OBJECTIVE: To develop and validate the Medication-Based
      Disease Burden Index (MDBI). METHODS: A list of medications corresponding to the
      leading causes of global death was pilot tested and finalized by an expert panel.
      The resulting index was tested on drug regimens of patients at risk of medication
      misadventure. Criterion validity of the index was established against Charlson's
      index and Chronic Disease Score (CDS). Sensitivity, specificity, predictive
      validity, convergent and discriminant validity, and interrater and test-retest
      reliabilities of the index were also assessed. RESULTS: The MDBI consisting of
      specific medications for 20 chronic medical conditions and corresponding
      disability weightings was developed. The MDBI was tested on 317 patients with
      mean +/- SD Charlson's index scores of 2.8 +/- 2.2 and CDS scores of 7.3 +/- 2.8.
      Mean MDBI scores (0.33 +/- 0.28) demonstrated significant correlations with
      Charlson's index scores (r = 0.31; p < 0.001) and CDS (r = 0.53; p < 0.001). MDBI
      had satisfactory sensitivity and high specificity. Age of the patients and number
      of medications had significant correlation with the MDBI scores, but the MDBI
      scores were not significantly different in males and females. MDBI scores could
      successfully predict death and planned or unplanned readmissions (OR = 4.7, 95%
      CI 1.4 to 15.5; p = 0.01). MDBI demonstrated high inter-rater (intraclass
      correlation coefficient [ICC] = 0.99) and test-retest reliabilities (ICC = 0.98).
      CONCLUSIONS: Initial testing suggests that MDBI could offer an alternative low
      cost and convenient method for quantifying disease burden and predicting health
      outcomes.

PMID- 16569816
TI  - Effect of glucosamine on glucose control.
AB  - OBJECTIVE: To review the literature regarding the effect of glucosamine on
      glucose control. DATA SOURCES: English-language articles on the effects of
      administration of exogenous glucosamine on glucose control were identified
      through a search of MEDLINE (1966-March 2006), EMBASE (1988-March 2006), and
      International Pharmaceutical Abstracts (1970-March 2006) databases using the
      search terms glucosamine, blood glucose, and diabetes mellitus. Abstracts of
      articles were then reviewed to determine relevance to the topic. Bibliographies
      of selected articles were screened for other pertinent references. DATA
      SYNTHESIS: Theoretically, glucosamine may alter glucose metabolism. Insulin
      resistance has been noted following intravenous administration of glucosamine in
      animal studies; however, these findings have not been confirmed in humans.
      Alterations in glucose control have not been documented in long-term efficacy
      studies using oral glucosamine for osteoarthritis or in trials of short duration
      conducted in healthy or diabetic subjects. The long-term effects of glucosamine
      in patients with diabetes have yet to be established in well-controlled trials.
      CONCLUSIONS: Small, short-term studies suggest that glucosamine may be used in
      selected patients without affecting glucose control; however, data in patients
      with diabetes mellitus are limited, and close monitoring for potential changes in
      glucose control is recommended.

PMID- 16569817
TI  - BRAF and MEK mutations make a late entrance.
AB  - The small guanosine triphosphatase KRAS and the protein kinases BRAF, which is a
      mitogen-activated protein kinase kinase kinase (MAPKKK), and mitogen-activated
      protein kinase kinase 1 and 2 (MAPKK1/2, also known as MKK1/2 or MEK1/2) are
      signaling partners in the MAPK signal transduction pathway. They are involved in
      many biological processes and play crucial roles during embryonic development.
      When inappropriately expressed, KRAS, BRAF, and MEK1/2 are also frequently
      implicated in tumor progression. Hence, it might reasonably have been predicted
      that either loss- or gain-of-function germline mutations in the genes that encode
      them would cause embryonic death. However, in a surprising development, two
      articles report that germline mutations in the KRAS, BRAF, and MEK1/2 genes are
      associated with cardio-facio-cutaneous (CFC) syndrome. This unexpected discovery
      demonstrates that mutations in KRAS, BRAF, and MEK can pass through the germline
      to cause specific developmental syndromes. This finding will undoubtedly
      stimulate further research into the function of these proteins in development and
      in both inherited and sporadic cancers.

PMID- 16569818
TI  - Multiple thermometers in mammalian cells: why do cells from homeothermic
      organisms need to measure temperature?
AB  - Mammalian cells activate survival signaling pathways and other protective
      mechanisms or induce apoptotic cell death in response to heat stress at
      temperatures beyond the range of those that they would ever be expected to
      encounter in vivo. Recent work has demonstrated that heat shock directly
      activates the apoptotic proteins Bax and Bak, suggesting that these polypeptides
      function as cellular thermometers in the mitochondrial apoptotic pathway. Here we
      review this and other heat-activated signaling pathways and propose a model that
      postulates that these "cellular thermometers" are not designed to sense
      physiologically irrelevant temperatures but rather to detect a general buildup of
      abnormal proteins in the cytosol and other cellular compartments.

PMID- 16569820
TI  - Maribavir pharmacokinetics and the effects of multiple-dose maribavir on
      cytochrome P450 (CYP) 1A2, CYP 2C9, CYP 2C19, CYP 2D6, CYP 3A, N
      acetyltransferase-2, and xanthine oxidase activities in healthy adults.
AB  - Maribavir (1263W94, VP-41263) is an oral anticytomegalovirus agent under clinical
      development. The pharmacokinetics and safety of maribavir and the effects of
      maribavir on the activities of cytochrome P450 (CYP) 1A2, CYP 2C9, CYP 2C19, CYP
      2D6, CYP 3A, N-acetyltransferase-2 (NAT-2), and xanthine oxidase (XO) were
      evaluated in a randomized, double-blind, placebo-controlled study. Twenty healthy
      subjects received a five-drug phenotyping cocktail of caffeine (CYP 1A2, NAT-2,
      XO), warfarin plus vitamin K (CYP 2C9), omeprazole (CYP 2C19), dextromethorphan
      (CYP 2D6), and midazolam (CYP 3A) 4 days before and after 7 days of treatment
      with maribavir at 400 mg twice daily (16 subjects) or placebo (4 subjects) for 10
      days. Maribavir did not affect the CYP 1A2, CYP 2C9, CYP 3A, NAT-2, or XO
      activities. Bioequivalence was not demonstrated for CYP 2C19 and CYP 2D6,
      suggesting a decrease or inhibition of CYP 2C19 and CYP 2D6 activities. The
      pharmacokinetics of maribavir following a single dose and after 10 days of
      treatment were similar, with minimal accumulation at steady state. Maribavir was
      safe and well tolerated. Taste disturbance was the most frequently reported
      adverse event. These results will further guide evaluation of the drug
      interaction potential and clinical development of maribavir.

PMID- 16569821
TI  - Structure-activity relationships of aminocoumarin-type gyrase and topoisomerase
      IV inhibitors obtained by combinatorial biosynthesis.
AB  - Novobiocin and clorobiocin are gyrase inhibitors produced by Streptomyces
      strains. Structurally, the two compounds differ only by substitution at two
      positions: CH3 versus Cl at position 8' of the aminocoumarin ring and carbamoyl
      versus 5-methyl-pyrrol-2-carbonyl (MePC) at the 3"-OH of noviose. Using genetic
      engineering, we generated a series of analogs carrying H, CH3, or Cl at 8' and H,
      carbamoyl, or MePC at 3"-OH. Comparison of the gyrase inhibitory activities of
      all nine structural permutations confirmed that acylation of 3"-OH is essential
      for activity, with MePC being more effective than carbamoyl. Substitution at 8'
      further enhanced activity, but the effect of CH3 or Cl depended on the nature of
      the acyl group at 3": in the presence of carbamoyl at 3", CH3 resulted in higher
      activity; in the presence of MePC at 3", Cl resulted in higher activity. This
      suggests that the structures of both natural compounds are highly evolved for
      optimal interaction with gyrase. In a second series of experiments, clorobiocin
      derivatives with and without the methyl group at 4"-OH of noviose, and with
      different positions of the MePC group of noviose, were tested. Again clorobiocin
      was superior to all of its analogs. The activities of all compounds were also
      tested against topoisomerase IV (topo IV). Clorobiocin stood out as a remarkably
      effective topo IV inhibitor. The relative activities of the different compounds
      toward topo IV showed a pattern similar to that of the relative gyrase-inhibitory
      activities. This is the first report of a systematic evaluation of a series of
      aminocoumarins against both gyrase and topo IV. The results give further insight
      into the structure-activity relationships of aminocoumarin antibiotics.

PMID- 16569822
TI  - Organization of tn2610 containing two transposition modules.
AB  - Transposon Tn2610, found in a conjugative plasmid from an Escherichia coli
      isolate recovered at a hospital in Chiba, Japan, in 1975, was completely
      sequenced. Tn2610 is 23,883 bp long and is bracketed by two transposition
      modules, a Tn1721-like module and a Tn21-derived module, which correspond,
      respectively, to the long inverted repeats IRa and IRb previously described for
      this transposon. Although both tnpA genes are intact, only that in the Tn21
      derived module (IRb) functions in the transposition, while that in the Tn1721
      derived module (IRa) cannot recognize the 38-bp imperfect repeat at the end of
      the IRb element. Both tnpR and res are present in IRa, while the tnpR gene of IRb
      is interrupted by the insertion of an IS26 insertion element. The intervening
      region, between the res site of the Tn1721 module and IS26, carries multiple
      integron-associated resistance genes within a Tn21 backbone, including a region
      identical to that found in the genome of Salmonella enterica serovar Typhimurium
      DT104. These findings suggest that Tn2610 originated from Tn1721 and Tn21, with
      extensive recombination events with other elements which have resulted in a
      complex mosaic structure.

PMID- 16569819
TI  - Beta-lactamase nomenclature.

PMID- 16569823
TI  - Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce
      significant changes in echinocandin susceptibility.
AB  - The micafungin and caspofungin susceptibilities of Candida albicans laboratory
      and clinical isolates and of Saccharomyces cerevisiae strains stably
      hyperexpressing fungal ATP-binding cassette (ABC) or major facilitator
      superfamily (MFS) transporters involved in azole resistance were determined using
      three separate methods. Yeast strains hyperexpressing individual alleles of ABC
      transporters or an MFS transporter from C. albicans gave the expected resistance
      profiles for the azoles fluconazole, itraconazole, and voriconazole. The strains
      hyperexpressing CDR2 showed slightly decreased susceptibility to caspofungin in
      agar plate drug resistance assays, as previously reported, but increased
      susceptibility to micafungin compared with either the strains hyperexpressing
      CDR1 or the null parent deleted of seven ABC transporters. The strains
      hyperexpressing CDR1 showed slightly decreased susceptibility to micafungin in
      these assays. A C. albicans clinical isolate overexpressing both Cdr1p and Cdr2p
      relative to its azole-sensitive isogenic progenitor acquired resistance to azole
      drugs and showed reduced susceptibility to caspofungin and slightly increased
      susceptibility to micafungin in agar plate drug resistance assays. None of the
      strains showed significant resistance to micafungin or caspofungin in liquid
      microdilution susceptibility assays. The antifungal activities of micafungin and
      caspofungin were similar in agarose diffusion assays, although the shape and size
      of the caspofungin inhibitory zones were affected by medium composition. The
      assessment of micafungin and caspofungin potency is therefore assay dependent;
      the differences seen with agar plate drug resistance assays occur over narrow
      ranges of echinocandin concentrations and are not of clinical significance.

PMID- 16569825
TI  - Comparing gatifloxacin and clarithromycin in pneumonia symptom resolution and
      process of care.
AB  - In looking for outcome differences beyond rates of cure, we prospectively
      compared the symptom resolution, side effects, and processes of care between the
      use of clarithromycin and gatifloxacin for the treatment of radiographically
      confirmed community-acquired pneumonia. We conducted a multicenter, randomized,
      open-label study comparing gatifloxacin monotherapy to clarithromycin alone or
      combined with ceftriaxone for patients with multiple risk factors. We measured
      the return to usual activities and symptoms over seven interviews ending 42 days
      after randomization. Admission and hospital discharge decision support were
      provided to treating physicians. We enrolled 266 patients over the age of 18
      years between September 2000 and June 2003. The groups were similar in age and
      gender, with a mean age of 53.5+/-19.4 years, and were 54% female. Patient
      severity as determined by the number of risk factors and the Pneumonia Severity
      Index was similar between groups; 95% of the patients were low risk. A total of
      91% of patients completed at least five of seven symptom interviews. In the
      clarithromycin study arm, 64% received concomitant therapy with ceftriaxone. We
      found no significant difference in return to usual activities, pneumonia-specific
      symptom scores, and 12-item short-form health survey scores. Individual symptom
      scores were similar except for bad taste and injection site soreness, which were
      higher in clarithromycin patients. The rates of hospital admission and length of
      stay were similar. The cost of antibiotic was higher in the clarithromycin group:
      $257 versus $110 for gatifloxacin. We found that gatifloxacin monotherapy is
      similar to clarithromycin given with or without ceftriaxone for the treatment of
      community-acquired pneumonia, except that antibiotic cost, bad taste, and
      injection site soreness favor the use of gatifloxacin.

PMID- 16569824
TI  - Distribution of florfenicol resistance genes fexA and cfr among chloramphenicol
      resistant Staphylococcus isolates.
AB  - A total of 302 chloramphenicol-resistant Staphylococcus isolates were screened
      for the presence of the florfenicol/chloramphenicol resistance genes fexA and cfr
      and their localization on mobile genetic elements. Of the 114 isolates from
      humans, only a single Staphylococcus aureus isolate showed an elevated MIC to
      florfenicol, but did not carry either of the known resistance genes, cfr or fexA.
      In contrast, 11 of the 188 staphylococci from animal sources were considered
      florfenicol resistant and carried either cfr (one isolate), fexA (five isolates),
      or both resistance genes (five isolates). In nine cases we confirmed that these
      genes were carried on a plasmid. Five different types of plasmids could be
      differentiated on the basis of their sizes, restriction patterns, and resistance
      genes. The gene fexA, which has previously been shown to be part of the
      nonconjugative transposon Tn558, was identified in 10 of the 11 resistant
      isolates from animals. PCR assays were developed to detect different parts of
      this transposon as well as their physical linkage. Complete copies of Tn558 were
      found in five different isolates and shown by inverse PCR to be functionally
      active. Truncated copies of Tn558, in which the tnpA-tnpB area was in part
      deleted by the integration of a 4,674-bp segment including the gene cfr and a
      novel 2,446-bp IS21-like insertion sequence, were seen in a plasmid present in
      three staphylococcal isolates.

PMID- 16569826
TI  - Determinants of rifampin, isoniazid, pyrazinamide, and ethambutol
      pharmacokinetics in a cohort of tuberculosis patients.
AB  - Evaluation of sources of pharmacokinetic variation can facilitate optimization of
      tuberculosis treatment regimens by identification of avoidable sources of
      variation and of risk factors for low or high drug concentrations in patients.
      Our objective was to describe the pharmacokinetics of rifampin, isoniazid,
      pyrazinamide, and ethambutol in a cohort of tuberculosis patients established on
      first-line treatment regimens and to evaluate the determinants of pharmacokinetic
      variation. Plasma concentration-time profiles were determined for each of the
      drugs in 142 patients with drug-sensitive pulmonary tuberculosis after 2 months
      of daily treatment in hospital. Pharmacokinetic measures were described by
      noncompartmental analysis. Multiple linear regression was used to evaluate the
      patient and the treatment factors associated with variation of the area under the
      concentration-time curve from 0 to 8 h. Several factors independently associated
      with variations in antituberculosis drug concentrations were identified: human
      immunodeficiency virus infection was associated with 39% and 27% reductions for
      rifampin and ethambutol, respectively; formulation factors were determinants of
      rifampin and isoniazid bioavailability; female patients had increased rifampin
      and isoniazid concentrations but reduced ethambutol concentrations; older
      patients had higher levels of isoniazid and ethambutol; patients with a history
      of previous antituberculosis treatment had lower ethambutol concentrations; and
      the dose per kilogram of body weight was associated with the concentrations of
      all four agents. Further studies are required to assess the implications of
      variations in antituberculosis drug concentrations for efficacy and safety before
      decisions are made to change the dosing strategy in patients at risk.

PMID- 16569827
TI  - qnrB, another plasmid-mediated gene for quinolone resistance.
AB  - A novel plasmid-mediated quinolone resistance gene, qnrB, has been discovered in
      a plasmid encoding the CTX-M-15 beta-lactamase from a Klebsiella pneumoniae
      strain isolated in South India. It has less than 40% amino acid identity with the
      original qnr (now qnrA) gene or with the recently described qnrS but, like them,
      codes for a protein belonging to the pentapeptide repeat family. Strains with
      qnrB demonstrated low-level resistance to all quinolones tested. The gene has
      been cloned in an expression vector attaching a polyhistidine tag, which
      facilitated purification to >or=95% homogeneity. As little as 5 pM of QnrB-His6
      protected purified DNA gyrase against inhibition by 2 microg/ml (6 microM)
      ciprofloxacin. With a PCR assay qnrB has been detected in Citrobacter koseri,
      Enterobacter cloacae, and Escherichia coli isolates from the United States,
      linked to SHV-12 beta-lactamase and coding for a product differing in five amino
      acids from the Indian (now QnrB1) variety. The qnrB gene has been found near
      Orf1005 in some, but not all, plasmids and in association with open reading
      frames matching known chromosomal genes, suggesting that it too was acquired by
      plasmids from an as-yet-unknown bacterial source.

PMID- 16569828
TI  - Staphylococcus aureus CcpA affects virulence determinant production and
      antibiotic resistance.
AB  - Carbon catabolite protein A (CcpA) is known to function as a major regulator of
      gene expression in different gram-positive organisms. Deletion of the ccpA
      homologue (saCOL1786) in Staphylococcus aureus was found to affect growth,
      glucose metabolization, and transcription of selected virulence determinants. In
      liquid culture, deletion of CcpA decreased the growth rate and yield; however,
      the effect was only transient during the exponential-growth phase as long as
      glucose was present in the medium. Depletion of glucose and production of lactate
      was delayed, while the level of excretion of acetate was less affected and was
      even higher in the mutant culture. On solid medium, in contrast, growth of the
      DeltaccpA mutant resulted in smaller colonies containing a lower number of CFU
      per colony. Deletion of CcpA had an effect on the expression of important
      virulence factors of S. aureus by down-regulating RNAIII, the effector molecule
      of the agr locus, and altering the transcription patterns of hla, encoding alpha
      hemolysin, and spa, encoding protein A. CcpA inactivation markedly reduced the
      oxacillin resistance levels in the highly methicillin-resistant S. aureus strain
      COLn and the teicoplanin resistance level in a glycopeptide-intermediate
      resistant S. aureus strain. The presence of CcpA in the capsular polysaccharide
      serotype 5 (CP5)-producing strain Newman abolished capsule formation and
      decreased cap operon transcription in the presence of glucose. The staphylococcal
      CcpA thus not only is involved in the regulation of carbon metabolism but seems
      to function as a modulator of virulence gene expression as well.

PMID- 16569829
TI  - Real-time reverse transcription-PCR quantification of cytokine mRNA expression in
      golden Syrian hamster infected with Leishmania infantum and treated with a new
      amphotericin B formulation.
AB  - A real-time quantitative reverse transcription-PCR assay was developed for the
      quantification of cytokine mRNA expression in the golden Syrian hamster
      Mesocricetus auratus infected with Leishmania infantum and treated with
      amphotericin B (AMB) formulated in microspheres made of human serum albumin
      (HSA). Treatment was administered intravenously on days 69, 71, and 73
      postinfection (p.i.) with 10(7) metacyclic promastigotes, at doses of 2 and 40
      mg/kg of AMB. High infection levels were recorded for untreated animals by day 76
      p.i., with parasite loads always about 2 log10 per gram higher in the liver than
      in the spleen. Treatment was highly effective with both doses, but at 40 mg/kg,
      almost complete parasite elimination was achieved. mRNA expression of gamma
      interferon (IFN-gamma) and, to a lesser extent, tumor necrosis factor alpha (TNF
      alpha) and transforming growth factor beta (TGF-beta) in spleen cells was up
      regulated in most animals of the untreated group. The mRNA expression of
      interleukin-4 was strongly down-regulated in untreated as well as treated
      infected animals. Treatment with the lower dose of AMB-HSA down-regulated the
      mRNA expression of IFN-gamma and TNF-alpha, with no effect on the deactivating
      cytokine TGF-beta. In contrast, treatment with the higher dose (40 mg/kg) of the
      formulation caused moderate up-regulation of IFN-gamma and TNF-alpha and strong
      suppression of TGF-beta. Treatment of noninfected animals did not alter the
      cytokine expression pattern with regard to untreated controls. Our results
      suggest that treatment of L. infantum-infected Syrian hamsters with highly
      effective nontoxic doses of AMB-HSA causes deactivation of the anti-inflammatory
      cytokine TGF-beta, which in turn results in up-regulation of the Th1 cytokines
      IFN-gamma and TNF-alpha.

PMID- 16569830
TI  - Bac 32, a novel bacteriocin widely disseminated among clinical isolates of
      Enterococcus faecium.
AB  - A total of 636 vancomycin-resistant Enterococcus faecium (VRE) isolates that had
      been obtained between 1994 and 1999 from the Medical School Hospital of the
      University of Michigan, Ann Arbor, were tested for bacteriocin production. Two
      hundred seventy-seven (44%) of the strains were bacteriocinogenic; and 193 of
      these exhibited activity against Enterococcus faecium, Enterococcus hirae, and
      Enterococcus durans. Strain VRE200 harbors the highly efficient conjugative
      gentamicin resistance plasmid pG200 (70 kb) and bacteriocin plasmid pTI1 (12.5
      kb). The bacteriocin encoded on pTI1 was designated bacteriocin 32 (Bac 32).
      Bacteriocin 32 was active against E. faecium, E. hirae, and E. durans but showed
      no activity against Listeria monocytogenes. The Bac 32 genetic locus consists of
      a bacteriocin gene (bacA) and an immunity gene (bacB). Neither of these genes
      showed significant homology to any known bacteriocin determinants. The deduced
      bacA product is 89 amino acids in length, with a putative signal peptide of 19
      amino acids at the N terminus. The bacB gene encodes a deduced 55-amino-acid
      protein without a signal sequence. One hundred eighty-nine strains (97.9%) of the
      193 strains with activity against the 3 test enterococcal strains gave rise to
      the expected specific PCR product with a primer specific for bacA, indicating
      that there is a high incidence of Bac 32 production among VRE clinical isolates.
      Data from Southern analyses of plasmid DNA from 189 of the Bac 32-producing
      strains with a plasmid pTI1-specific probe suggested that 137 (72.5%) of the
      strains harbored a pTI1-type plasmid. Bac 32 or Bac 32-type bacteriocin activity
      and the determinant genes were also identified in 22 (39.3%) of a total of 56
      vancomycin-sensitive E. faecium clinical isolates, which suggests that this
      bacteriocin is widely disseminated among E. faecium strains.

PMID- 16569831
TI  - Gentamicin causes apoptosis at low concentrations in renal LLC-PK1 cells
      subjected to electroporation.
AB  - Gentamicin accumulates in the lysosomes of kidney proximal tubular cells and
      causes apoptosis at clinically relevant doses. Gentamicin-induced apoptosis can
      be reproduced with cultured renal cells, but only at high extracellular
      concentrations (1 to 3 mM; 0.4 to 1.2 g/liter) because of its low level of
      uptake. We recently showed that gentamicin-induced apoptosis in LLC-PK1 cells
      involves a rapid (2-h) permeabilization of lysosomes and activation of the
      mitochondrial pathway of apoptosis (10 h). We now examine whether the delivery of
      gentamicin to the cytosol by electroporation would sensitize LLC-PK1 cells to
      apoptosis. Cells were subjected to eight pulses (1 ms) at 800 V/cm (square waves)
      in the presence of gentamicin (3 microM to 3 mM; 1.2 mg/liter to 1.2 g/liter);
      returned to gentamicin-free medium; and examined at 8 h for their Bax (a marker
      of mitochondrial pathway activation) contents by Western blotting and competitive
      reverse transcriptase PCR and at 24 h for apoptosis by 4',6'-diamidino-2'
      phenylindole staining (confirmed by electron microscopy) and for necrosis (by
      determination of lactate dehydrogenase release). Nonelectroporated cells were
      incubated with gentamicin for 8 and 24 h. Significant increases in Bax levels (8
      h) and apoptosis (24 h) were detected with 0.03 mM (13.2 mg/liter) gentamicin in
      electroporated cells compared with those achieved with 2 mM (928 mg/liter) in
      incubated cells. The increase in the Bax level was not associated with an
      increase in the level of its mRNA but was associated with the accumulation of
      ubiquitinated forms (probably as a result of impairment of its degradation by the
      proteasome). Assay of cell-associated gentamicin showed a marked, immediate, but
      transient accumulation in electroporated cells, whereas a slow, steady uptake was
      detected in incubated cells. The data indicate that cytosolic gentamicin triggers
      apoptosis. Sequestration of gentamicin in lysosomes would, to some extent,
      protect against apoptosis.

PMID- 16569832
TI  - Comparative pharmacokinetics and pharmacodynamic target attainment of ertapenem
      in normal-weight, obese, and extremely obese adults.
AB  - Little is known of the effects of obesity on ertapenem drug disposition and
      pharmacodynamics. Thirty healthy volunteers in three body mass index (BMI) groups
      (10 per group), normal weight (BMI, 18.5 to 24.9 kg/m2), class I-II obesity (BMI,
      30 to 39.9 kg/m2), and class III obesity (BMI, >or=40 kg/m2), were administered a
      1-g dose of ertapenem. Serum concentrations were obtained over 24 h. Population
      pharmacokinetic data were obtained using a nonparametric adaptive grid followed
      by Monte Carlo simulation to determine the probability of obtaining the free drug
      exposure targets of the time that the free drug concentration remains above the
      MIC (fT>MIC) of 20% and 40% for bacteriostatic and maximal bactericidal activity,
      respectively. Compared to the subjects in the obese groups, area under the
      concentration-time curve from 0 h to infinity was significantly higher in the
      normal-weight subjects, whereas the total central compartment volume was higher
      in the class III obese subjects (P<or=0.05). Achieving a bacteriostatic target of
      fT>MIC of 20% with a 90% probability was attained at MICs of <or=0.5 microg/ml
      for normal-weight subjects. Class I-II and class III obese subjects were able to
      achieve this target only at a MIC of <or=0.25 microg/ml. For maximal bactericidal
      activity (fT>MIC, 40%), no group attained the target at the 90% probability level
      at any tested MIC. The results suggest that the standard 1-g ertapenem dose may
      not provide adequate drug exposure for any body mass index classification for
      MICs in excess of 0.25 to 0.5 microg/ml.

PMID- 16569833
TI  - In vitro characterization of the antibacterial spectrum of novel bacterial type
      II topoisomerase inhibitors of the aminobenzimidazole class.
AB  - Antibiotics with novel mechanisms of action are becoming increasingly important
      in the battle against bacterial resistance to all currently used classes of
      antibiotics. Bacterial DNA gyrase and topoisomerase IV (topoIV) are the familiar
      targets of fluoroquinolone and coumarin antibiotics. Here we present the
      characterization of two members of a new class of synthetic bacterial topoII
      ATPase inhibitors: VRT-125853 and VRT-752586. These aminobenzimidazole compounds
      were potent inhibitors of both DNA gyrase and topoIV and had excellent
      antibacterial activities against a wide spectrum of problematic pathogens
      responsible for both nosocomial and community-acquired infections, including
      staphylococci, streptococci, enterococci, and mycobacteria. Consistent with the
      novelty of their structures and mechanisms of action, antibacterial potency was
      unaffected by commonly encountered resistance phenotypes, including
      fluoroquinolone resistance. In time-kill assays, VRT-125853 and VRT-752586 were
      bactericidal against Staphylococcus aureus, Streptococcus pneumoniae,
      Enterococcus faecalis, and Haemophilus influenzae, causing 3-log reductions in
      viable cells within 24 h. Finally, similar to the fluoroquinolones, relatively
      low frequencies of spontaneous resistance to VRT-125853 and VRT-752586 were
      found, a property consistent with their in vitro dual-targeting activities.

PMID- 16569835
TI  - Rapid microbiologic and pharmacologic evaluation of experimental compounds
      against Mycobacterium tuberculosis.
AB  - The assessment of physiochemical and pharmacological properties at early stages
      of drug discovery can accelerate the conversion of hits and leads into candidates
      for further development. A strategy for streamlined evaluation of compounds
      against Mycobacterium tuberculosis in the early preclinical stage is presented in
      this report. As a primary assay to rapidly select experimental compounds with
      sufficient in vitro activity, the growth inhibition microtiter plate assay was
      devised as an alternative to current methods. This microdilution plate assay is a
      liquid culture method based on spectrophotometric readings of the bacillary
      growth. The performance of this method was compared to the performance of two
      established susceptibility methods using clinical available tuberculosis (TB)
      drugs. Data generated from all three assays were similar for all of the tested
      compounds. A second simple bioassay was devised to assess the oral
      bioavailability of compounds prior to extensive in vivo efficacy testing. The
      bioassay estimates drug concentrations in collected serum samples by a
      microdilution MIC plate method using M. tuberculosis. In the same assay, the MIC
      of the compound is also determined in the presence of 10% mouse serum as an
      indication of protein binding. The method was validated using different
      clinically available TB drugs, and results are discussed in this report. With
      these methodological advances, screening of compounds against tuberculosis in the
      preclinical phase will be rapid, can be adapted to semi-high-throughput
      screening, and will add relevant physicochemical and basic pharmacological
      criteria to the decision process of drug discovery.

PMID- 16569834
TI  - Nanodisk-associated amphotericin B clears Leishmania major cutaneous infection in
      susceptible BALB/c mice.
AB  - Nanometer-scale, apolipoprotein-stabilized phospholipid bilayer disk complexes
      (nanodisks [ND]) harboring the toxic and poorly soluble antileishmanial agent
      amphotericin B (AMB) were examined for efficacy in treatment of Leishmania major
      infected BALB/c mice (Mus musculus). L. major-infected mice were
      intraperitoneally (i.p.) treated with AMB-ND in 0-, 1-, and 5-mg/kg doses at 24
      h, 48 h, and 4, 7, 14, and 21 days postinfection in two experiments. L. major
      infected mice were i.p. treated with phosphate-buffered saline, 5 mg/kg AMB-ND,
      or 5 mg/kg lipid-associated amphotericin B (liposomal amphotericin B, AmBisome)
      at 24 h, 48 h, and 10, 20, 30, and 40 days postinfection in one experiment.
      Parasite numbers, footpad lesion size progression, and development of cytokine
      responses were assayed at days 7, 15, 30, 50, 140, and 250 or at days 14, 30, 50,
      95, and 140 postinfection. Mice administered AMB-ND in 1- or 5-mg/kg doses were
      significantly protected from L. major, displaying decreases in lesion size and
      parasite burden, particularly at the 5-mg/kg dosage level. In contrast to the
      i.p. treated AmBisome group, BALB/c mice treated with i.p. AMB-ND completely
      cleared an L. major infection by 140 to 250 days postinfection, with no lesions
      remaining and no parasites isolated from infected animals. Restimulated mixed
      lymphocyte culture cytokine responses (interleukin-4 [IL-4], IL-12, IL-10, NO,
      and gamma interferon) were unchanged by AMB-ND administration compared to
      controls. The marked clearance of Leishmania parasites from a susceptible strain
      of mice without an appreciable change in the cytokine response suggests that AMB
      ND represent a potentially useful formulation for treatment of intrahistiocytic
      organisms.

PMID- 16569836
TI  - Activity of cecropin A-melittin hybrid peptides against colistin-resistant
      clinical strains of Acinetobacter baumannii: molecular basis for the differential
      mechanisms of action.
AB  - Acinetobacter baumannii has successfully developed resistance against all common
      antibiotics, including colistin (polymyxin E), the last universally active drug
      against this pathogen. The possible widespread distribution of colistin-resistant
      A. baumannii strains may create an alarming clinical situation. In a previous
      work, we reported differences in lethal mechanisms between polymyxin B (PXB) and
      the cecropin A-melittin (CA-M) hybrid peptide CA(1-8)M(1-18)
      (KWKLFKKIGIGAVLKVLTTGLPALIS-NH2) on colistin-susceptible strains (J. M. Saugar,
      T. Alarcon, S. Lopez-Hernandez, M. Lopez-Brea, D. Andreu, and L. Rivas,
      Antimicrob. Agents Chemother. 46:875-878, 2002). We now demonstrate that CA(1
      8)M(1-18) and three short analogues, namely CA(1-7)M(2-9) (KWKLFKKIGAVLKVL-NH2),
      its Nalpha-octanoyl derivative (Oct-KWKLFKKIGAVLKVL-NH2), and CA(1-7)M(5-9)
      (KWKLLKKIGAVLKVL-NH2) are active against two colistin-resistant clinical strains.
      In vitro, resistance to colistin sulfate was targeted to the outer membrane, as
      spheroplasts were equally lysed by a given peptide, regardless of their
      respective level of colistin resistance. The CA-M hybrids were more efficient
      than colistin in displacing lipopolysaccharide-bound dansyl-polymyxin B from
      colistin-resistant but not from colistin-susceptible strains. Similar improved
      performance of the CA-M hybrids in permeation of the inner membrane was observed,
      regardless of the resistance pattern of the strain. These results argue in favor
      of a possible use of CA-M peptides, and by extension other antimicrobial peptides
      with similar features, as alternative chemotherapy in colistin-resistant
      Acinetobacter infections.

PMID- 16569837
TI  - Clinical and economic impact of bacteremia with extended- spectrum-beta-lactamase
      producing Enterobacteriaceae.
AB  - We studied outcomes of extended-spectrum beta-lactamase (ESBL) production in
      Enterobacteriaceae bacteremia. Inpatients with bacteremia caused by ESBL
      producing Escherichia coli, Klebsiella spp., or Proteus spp. (cases) were
      compared with patients with bacteremia caused by non-ESBL producers (controls).
      Outcomes included mortality, mortality due to infection, length of stay (LOS),
      delay in appropriate therapy (DAT), discharge to a chronic care facility, and
      hospital cost. Ninety-nine cases and 99 controls were enrolled. Thirty-five
      percent of cases died, versus 18% of controls (odds ratio [OR], 2.5; 95%
      confidence interval [CI], 1.3 to 4.7; P=0.01). Thirty percent of cases died due
      to infection, versus 16% of controls (OR, 2.3; 95% CI, 1.1 to 4.5; P=0.03). The
      median LOS after bacteremia for cases was 11 days (interquartile range, 5 to 21),
      versus 5 days for controls (interquartile range, 3 to 9) (P<0.001). DAT occurred
      in 66% of cases, versus 7% of controls (OR, 25.1; 95% CI, 10.5 to 60.2; P<0.001).
      Cases were more likely than controls to be discharged to chronic care (52% versus
      21%; OR, 4.0; 95% CI, 1.9 to 8.3; P<0.001). The average hospital cost for cases
      was 65,509 Israeli shekels, versus 23,538 shekels for controls (P<0.001). After
      adjusting for differences between groups by using multivariable analysis, ESBL
      production remained a significant predictor of mortality (OR, 3.6; 95% CI, 1.4 to
      9.5; P=0.008), increased LOS (1.56-fold; P=0.001), DAT (OR, 25.1; 95% CI, 10.5 to
      60.2; P<0.001), and increased cost (1.57-fold; P=0.003). The mean increase in
      equivalent cost attributable to ESBL production was $9,620. ESBL production was
      associated with severe adverse outcomes, including higher overall and infection
      related mortality, increased LOS, DAT, discharge to chronic care, and higher
      costs.

PMID- 16569838
TI  - Garenoxacin treatment of experimental endocarditis caused by viridans group
      streptococci.
AB  - The activity of garenoxacin was compared to that of levofloxacin or penicillin in
      a rabbit model of Streptococcus mitis group (penicillin MIC, 0.125 microg/ml) and
      Streptococcus sanguinis group (penicillin MIC, 0.25 microg/ml) endocarditis.
      Garenoxacin and levofloxacin had MICs of 0.125 and 0.5 microg/ml, respectively,
      for both study isolates. Rabbits with catheter-induced aortic valve endocarditis
      were given no treatment, penicillin at 1.2x10(6) IU/8 h intramuscularly,
      garenoxacin at 20 mg/kg of body weight/12 h intravenously, or levofloxacin at 40
      mg/kg/12 h intravenously. For both isolates tested, garenoxacin area under the
      curve (AUC)/MIC and maximum concentration of drug in serum (Cmax)/MIC ratios were
      368 and 91, respectively. Rabbits were sacrificed after 3 days of treatment;
      cardiac valve vegetations were aseptically removed and quantitatively cultured.
      For S. mitis group experimental endocarditis, all studied antimicrobial agents
      were more active than no treatment (P<0.001), whereas for S. sanguinis group
      endocarditis, no studied antimicrobial agents were more active than no treatment.
      We conclude that AUC/MIC and Cmax/MIC ratios may not predict activity of some
      quinolones in experimental viridans group endocarditis and that garenoxacin and
      levofloxacin may not be ideal choices for serious infections caused by some
      quinolone-susceptible viridans group streptococci.

PMID- 16569839
TI  - Using bacteriophages to reduce formation of catheter-associated biofilms by
      Staphylococcus epidermidis.
AB  - Use of indwelling catheters is often compromised as a result of biofilm
      formation. This study investigated if hydrogel-coated catheters pretreated with a
      coagulase-negative bacteriophage would reduce Staphylococcus epidermidis biofilm
      formation. Biofilms were developed on hydrogel-coated silicone catheters
      installed in a modified drip flow reactor. Catheter segments were pretreated with
      the lytic S. epidermidis bacteriophage 456 by exposing the catheter lumen to a 10
      log-PFU/ml culture of the bacteriophage for 1 h at 37 degrees C prior to biofilm
      formation. The untreated mean biofilm cell count was 7.01+/-0.47 log CFU/cm2 of
      catheter. Bacteriophage treatment with and without supplemental divalent cations
      resulted in log-CFU/cm2 reductions of 4.47 (P<0.0001) and 2.34 (P=0.001),
      respectively. Divalent cation supplementation without bacteriophage treatment
      provided a 0.67-log-CFU/cm2 reduction (P=0.053). Treatment of hydrogel-coated
      silicone catheters with an S. epidermidis bacteriophage in an in vitro model
      system significantly reduced viable biofilm formation by S. epidermidis over a 24
      h exposure period, suggesting the potential of bacteriophage for mitigating
      biofilm formation on indwelling catheters and reducing the incidence of catheter
      related infections.

PMID- 16569840
TI  - MepR, a repressor of the Staphylococcus aureus MATE family multidrug efflux pump
      MepA, is a substrate-responsive regulatory protein.
AB  - The mepRAB gene cluster of Staphylococcus aureus encodes a MarR family repressor
      (MepR; known to repress mepA expression), a MATE family multidrug efflux pump
      (MepA), and a protein of unknown function (MepB). In this report, we show that
      MepR also is autoregulatory, repressing the expression of its own gene. Exposure
      of strains containing a mepR::lacZ fusion with mepR provided in trans under the
      control of an inducible promoter, or a mepA::lacZ fusion alone, to subinhibitory
      concentrations of MepA substrates resulted in variably increased expression
      mainly of mepA. Mobility shift assays revealed that MepR binds upstream of mepR
      and mepA, with an apparently higher affinity for the mepA binding site. MepA
      substrates abrogated MepR binding to each site in a differential manner, with the
      greatest effect observed on the MepR-mepA operator interaction. DNase I
      footprinting identified precise binding sites which included promoter motifs,
      inverted repeats, and transcription start sites for mepR and mepA, as well as a
      conserved GTTAG motif, which may be a signature recognition sequence for MepR.
      Analogous to other multidrug efflux pump regulatory proteins such as QacR, the
      substrate-MepR interaction likely results in its dissociation from its mepA, and
      in a more limited fashion its mepR, operator sites and relief of its repressive
      effect. The enhanced effect of substrates on mepA compared to mepR expression,
      and on the MepR-mepA operator interaction, results in significant relief of mepA
      and relative maintenance of mepR repression, leading to increased MepA protein
      unimpeded by MepR when the need for detoxification exists.

PMID- 16569841
TI  - In vitro analysis of ISEcp1B-mediated mobilization of naturally occurring beta
      lactamase gene blaCTX-M of Kluyvera ascorbata.
AB  - ISEcp1B has been reported to be associated with and to mobilize the emerging
      expanded-spectrum beta-lactamase blaCTX-M genes in Enterobacteriaceae. Thus, the
      ability of this insertion sequence to mobilize the blaCTX-M-2 gene was tested
      from its progenitor, Kluyvera ascorbata. Insertions of ISEcp1B upstream of the
      blaCTX-M-2 gene in K. ascorbata reference strain CIP7953 were first selected with
      cefotaxime (0.5 and 2 microg/ml). In those cases, ISEcp1B brought promoter
      sequences enhancing blaCTX-M-2 expression in K. ascorbata. Then, ISEcp1B-mediated
      mobilization of the blaCTX-M-2 gene from K. ascorbata to Escherichia coli J53 was
      attempted. The transposition frequency of ISEcp1B-blaCTX-M-2 occurred at (6.4+/
      0.5)x10(-7) in E. coli. Cefotaxime, ceftazidime, and piperacillin enhanced
      transposition, whereas amoxicillin, cefuroxime, and nalidixic acid did not.
      Transposition was also enhanced when studied at 40 degrees C.

PMID- 16569842
TI  - Evaluation of amphotericin B interpretive breakpoints for Candida bloodstream
      isolates by correlation with therapeutic outcome.
AB  - One hundred seven Candida bloodstream isolates (51 C. albicans, 24 C. glabrata,
      13 C. parapsilosis, 13 C. tropicalis, 2 C. dubliniensis, 2 C. krusei, and 2 C.
      lusitaniae strains) from patients treated with amphotericin B alone underwent in
      vitro susceptibility testing against amphotericin B using five different methods.
      Fifty-four isolates were from patients who failed treatment, defined as death 7
      to 14 days after the incident candidemia episode, having persistent fever of
      >or=5 days' duration after the date of the incident candidemia, or the recurrence
      of fever after two consecutive afebrile days while on antifungal treatment. MICs
      were determined by using the Clinical Laboratory Standards Institute (formally
      National Committee for Clinical Laboratory Standards) broth microdilution
      procedure with two media and by using Etest. Minimum fungicidal concentrations
      (MFCs) were also measured in two media. Broth microdilution tests with RPMI 1640
      medium generated a restricted range of MICs (0.125 to 1 microg/ml); the
      corresponding MFC values ranged from 0.5 to 4 microg/ml. Broth microdilution
      tests with antibiotic medium 3 produced a broader distribution of MIC and MFC
      results (0.015 to 0.25 microg/ml and 0.06 to 2 microg/ml, respectively). Etest
      produced the widest distribution of MICs (0.094 to 2 microg/ml). However, none of
      the test formats studied generated results that significantly correlated with
      therapeutic success or failure.

PMID- 16569843
TI  - Assessment of the paradoxical effect of caspofungin in therapy of candidiasis.
AB  - Paradoxical growth of some Candida albicans isolates in the presence of
      caspofungin (CAS) in vitro has been demonstrated previously. We sought to
      determine whether a similar phenomenon occurred in vivo. A systemic model of
      candidiasis was studied in CD-1 mice by intravenous inoculation of different
      isolates of C. albicans. Infected animals were treated with CAS at various
      dosages (0.01 to 20 mg/kg) and CFU remaining in the kidneys determined. Four
      clinical isolates that showed paradoxical growth in vitro and one that did not
      were tested. Recovery of CFU from the kidneys showed that dosages of CAS at 0.1
      mg/kg and above were efficacious in the reduction of C. albicans, but were not
      curative. Against isolates that show paradoxical growth in vitro, CAS was
      efficacious, but lacked dose responsiveness above 0.5 mg/kg against three of the
      four. One isolate, 95-68, showed paradoxical growth in vivo with significantly
      higher CFU recovered from mice given CAS at 20 mg/kg than those given CAS at 5
      mg/kg, but the effect was not reproducible in a subsequent experiment. When CAS
      was given prophylactically and therapeutically, improved efficacy and cure rate
      were observed. Overall, these data indicate that CAS is highly efficacious
      against systemic murine candidiasis and a paradoxical effect was not reproducibly
      demonstrated in vivo.

PMID- 16569844
TI  - Impact of Enterococcus faecalis on the bactericidal activities of arbekacin,
      daptomycin, linezolid, and tigecycline against methicillin-resistant
      Staphylococcus aureus in a mixed-pathogen pharmacodynamic model.
AB  - We inoculated an in vitro pharmacodynamic model simultaneously with clinical
      isolates of methicillin-resistant Staphylococcus aureus and an enterocin
      producing enterococcus (vancomycin-resistant Enterococcus faecalis, ampicillin
      susceptible) at 7 log10 CFU/ml to examine enterocin effects and antimicrobial
      activity on staphylococci. The investigated antimicrobial regimens were 100 mg
      arbekacin every 12 h (q12h), 6 mg daptomycin per kg of body weight/day, 600 mg
      linezolid q12h, and 100 mg tigecycline q24h alone and in combination (daptomycin,
      linezolid, and tigecycline) with arbekacin. Simulations were performed in
      triplicate; bacterial quantification occurred over 48 h, and development of
      resistance was evaluated throughout. When we evaluated the impact of
      antimicrobial activity against S. aureus alone, daptomycin demonstrated
      bactericidal activity (>or=3 log10 CFU/ml kill), whereas arbekacin, linezolid,
      and tigecycline displayed bacteriostatic activities (<3 log10 CFU/ml kill). In
      the mixed-pathogen model, early and distinctive stunting of S. aureus growth was
      noted (1.5 log CFU/ml difference) in the presence of enterocin-producing E.
      faecalis compared to growth controls run individually (P=0.02). Most noteworthy
      was that in the presence of enterocin-producing E. faecalis, bactericidal
      activity was observed with arbekacin and tigecycline and with the addition of
      arbekacin to linezolid. Antagonism was noted for the combination of tigecycline
      and arbekacin against S. aureus in the presence of enterocin-producing E.
      faecalis. Our research demonstrates that the inhibitory effect of E. faecalis
      contributed significantly to its overall antimicrobial impact on S. aureus. This
      contribution was enhanced or improved compared to the activity of each
      antimicrobial alone. Further research is warranted to determine the impact of
      polymicrobial infections on antimicrobial activity.

PMID- 16569845
TI  - Pharmacokinetics of tenofovir disoproxil fumarate and ritonavir-boosted
      saquinavir mesylate administered alone or in combination at steady state.
AB  - A phase I study was conducted to formally evaluate the steady-state
      pharmacokinetics (PK) of tenofovir disoproxil fumarate (TDF) and ritonavir (RTV)
      boosted saquinavir mesylate (SQV) when coadministered in healthy volunteers.
      Forty subjects received multiple doses of TDF (300 mg, once daily) and SQV/RTV
      (1,000 mg/100 mg, twice daily) alone and together under steady-state conditions
      in an open-label, fixed sequence design. Blood samples for tenofovir (TFV) and
      SQV/RTV PK were drawn over respective 24- and 12-h dosing intervals, and drug
      concentrations were measured by liquid chromatography-tandem mass spectrometry.
      Safety was assessed periodically by clinical and laboratory monitoring. Thirty
      two subjects completed the study and were fully evaluable; three subjects
      discontinued participation in the study due to adverse events, three subjects
      withdrew for personal reasons, and two subjects withdrew because of inadequate
      venous access for blood sampling. Steady-state TFV PK were not significantly
      altered upon coadministration with SQV/RTV. Steady-state SQV (administered as
      SQV/RTV) AUCtau, Cmax, and Ctau increased 29, 22, and 47%, respectively, upon
      coadministration with TDF, and all subjects achieved a Ctau of >100 ng/ml. These
      modestly increased SQV exposures are not clinically meaningful given its clinical
      use with RTV already results in >10-fold-higher SQV levels. Steady-state RTV
      AUCtau and Cmax levels were not significantly altered, whereas Ctau was 23%
      higher upon coadministration of SQV/RTV and TDF. Thus, no clinically relevant
      interactions between TDF and RTV-boosted SQV were observed under conditions
      simulating clinical practice.

PMID- 16569846
TI  - Time course of microbiologic outcome and gene expression in Candida albicans
      during and following in vitro and in vivo exposure to fluconazole.
AB  - Pharmacodynamics (PD) considers the relationship between drug exposure and
      effect. The two factors that have been used to distinguish the PD behaviors of
      antimicrobials are the impact of concentration on the extent of organism killing
      and the duration of persistent microbiologic suppression (postantibiotic effect).
      The goals of these studies were (i) to examine the relationship between
      antimicrobial PD and gene expression and (ii) to gain insight into the mechanism
      of fluconazole effects persisting following exposure. Microarrays were used to
      estimate the transcriptional response of Candida albicans to a supra-MIC F
      exposure over time in vitro. Fluconazole at four times the MIC was added to a log
      phase C. albicans culture, and cells were collected to determine viable growth
      and for microarray analyses. We identified differential expression of 18% of all
      genes for at least one of the time points. More genes were upregulated (n=1,053
      [16%]) than downregulated (174 [3%]). Of genes with known function that were
      upregulated during exposure, most were related to plasma membrane/cell wall
      synthesis (18%), stress responses (7%), and metabolism (6%). The categories of
      downregulated genes during exposure included protein synthesis (15%), DNA
      synthesis/repair (7%), and transport (7%) genes. The majority of genes identified
      at the postexposure time points were from the protein (17%) and DNA (7%)
      synthesis categories. In subsequent studies, three genes (CDR1, CDR2, and ERG11)
      were examined in greater detail (more concentration and time points) following
      fluconazole exposure in vitro and in vivo. Expression levels from the in vitro
      and in vivo studies were congruent. CDR1 and CDR2 transcripts were reduced during
      in vitro fluconazole exposure and during supra-MIC exposure in vivo. However, in
      the postexposure period, the mRNA abundance of both pumps increased. ERG11
      expression increased during exposure and fell in the postexposure period. The
      expression of the three genes responded in a dose-dependent manner. In sum, the
      microarray data obtained during and following fluconazole exposure identified
      genes both known and unknown to be affected by this drug class. The expanded in
      vitro and in vivo expression data set underscores the importance of considering
      the time course of exposure in pharmacogenomic investigations.

PMID- 16569847
TI  - Triaryl pyrazoline compound inhibits flavivirus RNA replication.
AB  - Triaryl pyrazoline {[5-(4-chloro-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1
      yl]-phenyl-methanone} inhibits flavivirus infection in cell culture. The
      inhibitor was identified through high-throughput screening of a compound library
      using a luciferase-expressing West Nile (WN) virus infection assay. The compound
      inhibited an epidemic strain of WN virus without detectable cytotoxicity (a 50%
      effective concentration of 28 microM and a compound concentration of >or=300
      microM required to reduce 50% cell viability). Besides WN virus, the compound
      also inhibited other flaviviruses (dengue, yellow fever, and St. Louis
      encephalitis viruses), an alphavirus (Western equine encephalitis virus), a
      coronavirus (mouse hepatitis virus), and a rhabdovirus (vesicular stomatitis
      virus). However, the compound did not suppress an orthomyxovirus (influenza
      virus) or a retrovirus (human immunodeficiency virus type 1). Mode-of-action
      analyses in WN virus showed that the compound did not inhibit viral entry or
      virion assembly but specifically suppressed viral RNA synthesis. To examine the
      mechanism of inhibition of dengue virus, we developed two replicon systems for
      dengue type 1 virus: (i) a stable cell line that harbored replicons containing a
      luciferase reporter and a neomycin phosphotransferase selection marker and (ii) a
      luciferase-expressing replicon that could differentiate between viral translation
      and RNA replication. Analyses of the compound in the dengue type 1 virus replicon
      systems showed that it weakly suppressed viral translation but significantly
      inhibited viral RNA synthesis. Overall, the results demonstrate that triaryl
      pyrazoline exerts a broad spectrum of antiflavivirus activity through potent
      inhibition of viral RNA replication. This novel inhibitor could be developed for
      potential treatment of flavivirus infection.

PMID- 16569848
TI  - Novel carbapenem-hydrolyzing oxacillinase OXA-62 from Pandoraea pnomenusa.
AB  - Pandoraea spp. are gram-negative, glucose nonfermenting rods detectable in blood
      cultures and sputa of cystic fibrosis patients. They are resistant to various
      antibiotic groups, with imipenem being the only active beta-lactam. We isolated
      an imipenem-resistant (MIC, 64 microg/ml) Pandoraea pnomenusa strain from a
      cystic fibrosis patient. Cloning and sequencing identified two beta-lactamases of
      Bush group 2d, namely, the known OXA-33, located on an integron, and the novel
      carbapenem-hydrolyzing oxacillinase OXA-62. OXA-62 is only distantly related to
      other oxacillinases (OXA-50 being closest with 43% amino acid identity). It
      hydrolyzes penicillins, oxacillin, imipenem, and meropenem but not expanded
      spectrum cephalosporins. The blaOXA-62 gene is chromosome located. No
      transposable elements were found in its genetic neighborhood. With OXA-62
      specific primers, blaOXA-62 could be identified in all P. pnomenusa strains and
      appears to be species specific. This additional mechanism of carbapenem
      resistance further complicates the treatment of infections caused by P.
      pnomenusa.

PMID- 16569850
TI  - Contribution of rpoB2 RNA polymerase beta subunit gene to rifampin resistance in
      Nocardia species.
AB  - Nocardia species are gram-positive environmental saprophytes, but some cause the
      infectious disease nocardiosis. The complete genomic sequence of Nocardia
      farcinica IFM 10152 has been determined, and analyses indicated the presence of
      two different RNA polymerase beta subunit genes, rpoB and rpoB2, in the genome
      (J. Ishikawa, A. Yamashita, Y. Mikami, Y. Hoshino, H. Kurita, K. Hotta, T. Shiba,
      and M. Hattori, Proc. Natl. Acad. Sci. USA 101:14925-14930, 2004). These genes
      share 88.8% identity at the nucleotide level. Moreover, comparison of their amino
      acid sequences with those of other bacterial RpoB proteins suggested that the
      nocardial RpoB protein is likely to be rifampin (RIF) sensitive, whereas RpoB2
      protein contains substitutions at the RIF-binding region that are likely to
      confer RIF resistance. Southern analysis indicated that rpoB duplication is
      widespread in Nocardia species and is correlated with the RIF-resistant
      phenotype. The introduction of rpoB2 by using a newly developed Nocardia
      Escherichia coli shuttle plasmid vector and transformation system conferred RIF
      resistance to Nocardia asteroides IFM 0319T, which has neither RIF resistance nor
      rpoB duplication. Furthermore, unmarked rpoB2 deletion mutants of N. farcinica
      IFM 10152 showed no significant resistance to RIF. These results indicated the
      contribution of rpoB2 to RIF resistance in Nocardia species. Since this is the
      first example of genetic engineering of the Nocardia genome, we believe that this
      study, as well as our determination of the N. farcinica genome sequence, will be
      a landmark in Nocardia genetics.

PMID- 16569849
TI  - Activity and mechanism of action of N-methanocarbathymidine against herpesvirus
      and orthopoxvirus infections.
AB  - N-Methanocarbathymidine [(N)-MCT] is a conformationally locked nucleoside analog
      that is active against some herpesviruses and orthopoxviruses in vitro. The
      antiviral activity of this molecule is dependent on the type I thymidine kinase
      (TK) in herpes simplex virus and also appears to be dependent on the type II TK
      expressed by cowpox and vaccinia viruses, suggesting that it is a substrate for
      both of these divergent forms of the enzyme. The drug is also a good inhibitor of
      viral DNA synthesis in both viruses and is consistent with inhibition of the
      viral DNA polymerase once it is activated by the viral TK homologs. This
      mechanism of action explains the rather unusual spectrum of activity, which is
      limited to orthopoxviruses, alphaherpesviruses, and Epstein-Barr virus, since
      these viruses express molecules with TK activity that can phosphorylate and thus
      activate the drug. The compound is also effective in vivo and reduces the
      mortality of mice infected with orthopoxviruses, as well as those infected with
      herpes simplex virus type 1 when treatment is initiated 24 h after infection.
      These results indicate that (N)-MCT is active in vitro and in vivo, and its
      mechanism of action suggests that the molecule may be an effective therapeutic
      for orthopoxvirus and herpesvirus infections, thus warranting further
      development.

PMID- 16569852
TI  - Antitrypanosomal and antileishmanial activities of flavonoids and their
      analogues: in vitro, in vivo, structure-activity relationship, and quantitative
      structure-activity relationship studies.
AB  - Trypanosomiasis and leishmaniasis are important parasitic diseases affecting
      millions of people in Africa, Asia, and South America. In a previous study, we
      identified several flavonoid glycosides as antiprotozoal principles from a
      Turkish plant. Here we surveyed a large set of flavonoid aglycones and
      glycosides, as well as a panel of other related compounds of phenolic and
      phenylpropanoid nature, for their in vitro activities against Trypanosoma brucei
      rhodesiense, Trypanosoma cruzi, and Leishmania donovani. The cytotoxicities of
      more than 100 compounds for mammalian L6 cells were also assessed and compared to
      their antiparasitic activities. Several compounds were investigated in vivo for
      their antileishmanial and antitrypanosomal efficacies in mouse models. Overall,
      the best in vitro trypanocidal activity for T. brucei rhodesiense was exerted by
      7,8-dihydroxyflavone (50% inhibitory concentration [IC50], 68 ng/ml), followed by
      3-hydroxyflavone, rhamnetin, and 7,8,3',4'-tetrahydroxyflavone (IC50s, 0.5
      microg/ml) and catechol (IC50, 0.8 microg/ml). The activity against T. cruzi was
      moderate, and only chrysin dimethylether and 3-hydroxydaidzein had IC50s less
      than 5.0 microg/ml. The majority of the metabolites tested possessed remarkable
      leishmanicidal potential. Fisetin, 3-hydroxyflavone, luteolin, and quercetin were
      the most potent, giving IC50s of 0.6, 0.7, 0.8, and 1.0 microg/ml, respectively.
      7,8-Dihydroxyflavone and quercetin appeared to ameliorate parasitic infections in
      mouse models. Generally, the test compounds lacked cytotoxicity in vitro and in
      vivo. By screening a large number of flavonoids and analogues, we were able to
      establish some general trends with respect to the structure-activity
      relationship, but it was not possible to draw clear and detailed quantitative
      structure-activity relationships for any of the bioactivities by two different
      approaches. However, our results can help in directing the rational design of 7,8
      dihydroxyflavone and quercetin derivatives as potent and effective antiprotozoal
      agents.

PMID- 16569851
TI  - Involvement of the MexXY-OprM efflux system in emergence of cefepime resistance
      in clinical strains of Pseudomonas aeruginosa.
AB  - Cefepime (FEP) and ceftazidime (CAZ) are potent beta-lactam antibiotics with
      similar MICs (1 to 2 mug/ml) for wild-type strains of Pseudomonas aeruginosa.
      However, recent epidemiological studies have highlighted the occurrence of
      isolates more resistant to FEP than to CAZ (FEPr/CAZs profile). We thus
      investigated the mechanisms conferring such a phenotype in 38 clonally unrelated
      strains collected in two French teaching hospitals. Most of the bacteria (n=32;
      84%) appeared to stably overexpress the mexY gene, which codes for the RND
      transporter of the multidrug efflux system MexXY-OprM. MexXY up-regulation was
      the sole FEP resistance mechanism identified (n=12) or was associated with
      increased levels of pump MexAB-OprM (n=5) or MexJK (n=2), synthesis of secondary
      beta-lactamase PSE-1 (n=10), derepression of cephalosporinase AmpC (n=1),
      coexpression of both OXA-35 and MexJK (n=1), or production of both PSE-1 and
      MexAB-OprM (n=1). Down-regulation of the mexXY operon in seven selected strains
      by the plasmid-borne repressor gene mexZ decreased FEP resistance from two- to
      eightfold, thereby demonstrating the significant contribution of MexXY-OprM to
      the FEPr/CAZs phenotype. The six isolates of this series that exhibited wild-type
      levels of the mexY gene were found to produce beta-lactamase PSE-1 (n=1), OXA-35
      (n=4), or both PSE-1 and OXA-35 (n=1). Altogether, these data provide evidence
      that MexXY-OprM plays a major role in the development of FEP resistance among
      clinical strains of P. aeruginosa.

PMID- 16569853
TI  - Overexpression of the MDR1 gene is sufficient to confer increased resistance to
      toxic compounds in Candida albicans.
AB  - Overexpression of MDR1, which encodes a membrane transport protein of the major
      facilitator superfamily, is one mechanism by which the human fungal pathogen
      Candida albicans can develop increased resistance to the antifungal drug
      fluconazole and other toxic compounds. In clinical C. albicans isolates,
      constitutive MDR1 overexpression is accompanied by the upregulation of other
      genes, but it is not known if these additional alterations are required for Mdr1p
      function and drug resistance. To investigate whether MDR1 overexpression is
      sufficient to confer a drug-resistant phenotype in C. albicans, we expressed the
      MDR1 gene from the strong ADH1 promoter in C. albicans laboratory strains that
      did not express the endogenous MDR1 gene as well as in a fluconazole-resistant
      clinical C. albicans isolate in which the endogenous MDR1 alleles had been
      deleted and in a matched fluconazole-susceptible isolate from the same patient.
      Forced MDR1 overexpression resulted in increased resistance to the putative Mdr1p
      substrates cerulenin and brefeldin A, and this resistance did not depend on the
      additional alterations which occurred during drug resistance development in the
      clinical isolates. In contrast, artificial expression of the MDR1 gene from the
      ADH1 promoter did not enhance or only slightly enhanced fluconazole resistance,
      presumably because Mdr1p expression levels in the transformants were considerably
      lower than those observed in the fluconazole-resistant clinical isolate. These
      results demonstrate that MDR1 overexpression in C. albicans is sufficient to
      confer resistance to some toxic compounds that are substrates of this efflux pump
      but that the degree of resistance depends on the Mdr1p expression level.

PMID- 16569855
TI  - Pharmacodynamics of a new cephalosporin, PPI-0903 (TAK-599), active against
      methicillin-resistant Staphylococcus aureus in murine thigh and lung infection
      models: identification of an in vivo pharmacokinetic-pharmacodynamic target.
AB  - PPI-0903 is a new cephalosporin with broad-spectrum activity, including beta
      lactam-resistant Streptococcus pneumoniae and Staphylococcus aureus. We used the
      neutropenic murine thigh and lung infection models to examine the pharmacodynamic
      characteristics of PPI-0903. Serum drug levels following four fourfold-escalating
      single doses of PPI-0903 were measured by microbiologic assay. In vivo
      postantibiotic effects (PAEs) were determined after doses of 1.56, 6.25, 25, and
      100 mg/kg of body weight in mice infected with S. pneumoniae ATCC 10813, S.
      aureus ATCC 29213, or Escherichia coli ATCC 25922. Dose fractionation studies
      over a 24-h dose range of 0.39 to 1,600 mg/kg were administered every 3, 6, 12,
      or 24 hours. Nonlinear regression analysis was used to determine which
      pharmacokinetic-pharmacodynamic (PK-PD) index (total and free 65% drug) best
      correlated with CFU/thigh at 24 h. Similar to other beta-lactam antibiotics, PPI
      0903 produced short to modest in vivo PAEs with either S. pneumoniae or E. coli.
      The percent time that serum concentrations were above the MIC (%T>MIC) was the PK
      PD index that best correlated with efficacy (R2=84 to 88% for the three
      organisms, compared with 9 to 41% for peak/MIC and 30 to 82% for the area under
      the concentration-time curve/MIC). In subsequent studies we used the neutropenic
      murine thigh infection model to determine if the magnitude of the free-drug %
      T>MIC needed for efficacy of PPI-0903 varied among pathogens (including resistant
      strains). Mice infected with one of five isolates of S. pneumoniae, four isolates
      of S. aureus, or four gram-negative bacilli were treated for 24 h with 0.10 to
      400 mg/kg of PPI-0903 every 6 h. A sigmoid dose-response model was used to
      estimate the doses (mg/kg/24 h) required to achieve a net bacteriostatic affect
      over 24 h and to produce a reduction in the burden of organisms from the start of
      therapy by 1 and 2 log10 CFU/thigh. MICs ranged from 0.008 to 1 microg/ml.Mean
      free-drug %T >MICs the standard deviation associated with the static effect
      endpoint for S. pneumoniae, S. aureus, and gram-negative isolates were 39+/-9,
      26+/-8, and 47+/-8, respectively [corrected]. Methicillin and penicillin
      resistance did not alter the magnitude of free-drug %T>MIC required for efficacy.
      The free-drug %T>MIC necessary for efficacy was slightly reduced in animals with
      normal neutrophil counts. Treatment effect was similar in both the thigh and lung
      infection models. The pharmacodynamic characteristics of PPI-0903 are similar to
      those of other compounds within the cephalosporin class.

PMID- 16569854
TI  - Impaired target site penetration of vancomycin in diabetic patients following
      cardiac surgery.
AB  - Soft tissue infections constitute a serious complication following surgery in
      diabetic patients and frequently require the administration of vancomycin.
      However, despite antibiotic treatment, mortality of patients with postoperative
      infections remains high and might be related to an impaired penetration of anti
      infective agents to target tissues. Therefore, the present study was designed to
      measure vancomycin tissue concentrations in six diabetic and six nondiabetic
      patients after cardiac surgery. Vancomycin was administered as a continuous
      intravenous infusion at an infusion rate of 80 to 120 mg/h. Vancomycin
      concentrations in soft tissues and plasma were measured in all patients during
      steady state as "therapeutic window" concentrations in plasma by microdialysis on
      day 8+/-4 after initiation of vancomycin treatment. Vancomycin tissue
      concentrations in diabetic patients were significantly lower than in nondiabetics
      (3.7 mg/liter versus 11.9 mg/liter; P=0.002). The median
      vancomycintissue/vancomycinplasma concentration ratio was 0.1 in diabetic
      patients and 0.3 in nondiabetics (P=0.002). Our study demonstrated that
      vancomycin penetration into target tissues is substantially impaired in diabetic
      patients versus nondiabetics. Insufficient tissue concentrations could therefore
      possibly contribute to failure of antibiotic treatment and the development of
      antimicrobial resistance in diabetic patients.

PMID- 16569856
TI  - Candida glabrata PDR1, a transcriptional regulator of a pleiotropic drug
      resistance network, mediates azole resistance in clinical isolates and petite
      mutants.
AB  - Candida glabrata, a yeast with intrinsically low susceptibility to azoles,
      frequently develops increased azole resistance during prolonged treatment.
      Transposon mutagenesis revealed that disruption of CgPDR1 resulted in an 8- to 16
      fold increase in fluconazole susceptibility of C. glabrata. CgPDR1 is a homolog
      of Saccharomyces cerevisiae PDR1, which encodes a transcriptional regulator of
      multidrug transporters. Northern blot analyses indicated that CgPDR1 regulated
      both constitutive and drug-induced expression of CgCDR1, a multidrug transporter
      gene. In agreement with the Northern analysis, the Cgpdr1 mutant had increased
      rhodamine accumulation, in contrast to the decreased accumulation in the CgPDR1
      overexpressing strain. Northern analyses also indicated the importance of CgPDR1
      in fluconazole resistance arising during therapy. Two clinically resistant
      isolates had higher expression of CgPDR1 and CgCDR1 compared to their paired
      susceptible isolates. Integrative transformation of CgPDR1 from the two resistant
      isolates converted the Cgpdr1 mutant into azole-resistant strains with
      upregulated CgPDR1 expression. Two different amino acid substitutions, W297S in
      one isolate and F575L in the other, accounted for the upregulated CgPDR1
      expression and the resistance. Finally, CgPDR1 was shown to be required for the
      azole resistance due to mitochondrial deficiency. Thus, CgPDR1 encodes a
      transcriptional regulator of a pleiotropic drug resistance network and
      contributes to the azole resistance of clinical isolates and petite mutants.

PMID- 16569857
TI  - Phosphorothioate oligonucleotides inhibit human immunodeficiency virus type 1
      fusion by blocking gp41 core formation.
AB  - Several studies have shown that phosphorothioate oligodeoxynucleotides (PS-ONs)
      have a sequence-independent antiviral activity against human immunodeficiency
      virus type 1 (HIV-1). It has also been suggested that PS-ONs inhibit HIV-1 by
      acting as attachment inhibitors that bind to the V3 loop of gp120 and prevent the
      gp120-CD4 interaction. Here we show that PS-ONs (and their fully 2'-O-methylated
      derivatives) are potent inhibitors of HIV-1-mediated membrane fusion and HIV-1
      replication in a size-dependent, phosphorothioation-dependent manner. PS-ONs
      interact with a peptide derived from the N-terminal heptad repeat region of gp41,
      and the HIV-1 fusion-inhibitory activity of PS-ONs is closely correlated with
      their ability to block gp41 six-helix bundle formation, a critical step during
      the process of HIV-1 fusion with the target cell. These results suggest that the
      increased hydrophobicity of PS-ONs may contribute to their inhibitory activity
      against HIV-1 fusion and entry, because longer PS-ONs (>or=30 bases) which have a
      greater hydrophobicity are more potent in blocking the hydrophobic interactions
      involved in the gp41 six-helix bundle formation and inhibiting the HIV-1-mediated
      cell-cell fusion than shorter PS-ONs (<30 bases). This novel antiviral mechanism
      of action of long PS-ONs has implications for therapy against infection by HIV-1
      and other enveloped viruses with type I fusion proteins.

PMID- 16569859
TI  - Comparative analysis of chromosome-encoded microcins.
AB  - Microcins are ribosomally synthesized peptide antibiotics that are produced by
      enterobacterial strains. Although the first studies concentrated on plasmid
      encoded activities, in the last years three chromosome-encoded microcins have
      been described: H47, E492, and M. Here, a new microcin, I47, is presented as a
      fourth member of this group. Common features exhibited by chromosome-encoded
      microcins were searched for. The comparison of the genetic clusters responsible
      for microcin production revealed a preserved general scheme. The clusters
      essentially comprise a pair of activity-immunity genes which determine antibiotic
      specificity and a set of microcin maturation and secretion genes which are
      invariably present and whose protein products are highly homologous among the
      different producing strains. A strict functional relationship between the
      maturation and secretion pathways of microcins H47, I47, and E492 was
      demonstrated through genetic analyses, which included heterologous
      complementation assays. The peptide precursors of these microcins share a
      maturation process which implies the addition of a catecholate siderophore of the
      salmochelin type. Microcins thus acquire the ability to enter gram-negative cells
      through the catechol receptors. In addition, they employ a common mode of
      secretion to reach the external milieu by means of a type I export apparatus. The
      results presented herein lead us to propose that chromosome-encoded microcins
      constitute a defined subgroup of peptide antibiotics which are strictly related
      by their modes of synthesis, secretion, and uptake.

PMID- 16569858
TI  - Protease-stable polycationic photosensitizer conjugates between polyethyleneimine
      and chlorin(e6) for broad-spectrum antimicrobial photoinactivation.
AB  - We previously showed that covalent conjugates between poly-L-lysine and
      chlorin(e6) were efficient photosensitizers (PS) of both gram-positive and gram
      negative bacteria. The polycationic molecular constructs increased binding and
      penetration of the PS into impermeable gram-negative cells. We have now prepared
      a novel set of second-generation polycationic conjugates between chlorin(e6) and
      three molecular forms of polyethyleneimine (PEI): a small linear, a small cross
      linked, and a large cross-linked molecule. The conjugates were characterized by
      high-pressure liquid chromatography and tested for their ability to kill a panel
      of pathogenic microorganisms, the gram-positive Staphylococcus aureus and
      Streptococcus pyogenes, the gram-negative Escherichia coli and Pseudomonas
      aeruginosa, and the yeast Candida albicans, after exposure to low levels of red
      light. The large cross-linked molecule efficiently killed all organisms, while
      the linear conjugate killed gram-positive bacteria and C. albicans. The small
      cross-linked conjugate was the least efficient antimicrobial PS and its
      remarkably low activity could not be explained by reduced photochemical quantum
      yield or reduced cellular uptake. In contrast to polylysine conjugates, the PEI
      conjugates were resistant to degradation by proteases such as trypsin that
      hydrolyze lysine-lysine peptide bonds, The advantage of protease stability
      combined with the ready availability of PEI suggests these molecules may be
      superior to polylysine-PS conjugates for photodynamic therapy of localized
      infections.

PMID- 16569860
TI  - Efficacy of hospital germicides against adenovirus 8, a common cause of epidemic
      keratoconjunctivitis in health care facilities.
AB  - The inactivation of virus-contaminated nonporous inanimate surfaces was
      investigated using adenovirus type 8, a common cause of epidemic
      keratoconjunctivitis. A 10-microl inoculum of adenovirus was placed onto each
      stainless steel disk (1-cm diameter), and the inoculum was allowed to air dry for
      40 min. Twenty-one different germicides (including disinfectants and antiseptics)
      were selected for this study based on their current uses in health care. After a
      1- or 5-minute exposure to 50 microl of the germicide, the virus-germicide test
      mixture was neutralized and assayed for infectivity. Using an efficacy criterion
      of a 3-log10 reduction in the titer of virus infectivity and regardless of the
      virus suspending medium (i.e., hard water, sterile water, and hard water with 5%
      fetal calf serum), only five disinfectants proved to be effective against the
      test virus at 1 min: 0.55% ortho-phthalaldehyde, 2.4% glutaraldehyde, 2.65%
      glutaraldehyde, approximately 6,000 ppm chlorine, and approximately 1,900 ppm
      chlorine. Four other disinfectants showed effectiveness under four of the five
      testing conditions: 70% ethanol, 65% ethanol with 0.63% quaternary ammonium
      compound, 79.6% ethanol with 0.1% quaternary ammonium compound, and 0.2%
      peracetic acid. Of the germicides suitable for use as an antiseptic, 70% ethanol
      achieved a 3-log10 reduction under four of the five test conditions. These
      results emphasize the need for proper selection of germicides for use in
      disinfecting noncritical surfaces and semicritical medical devices, such as
      applanation tonometers, in order to prevent outbreaks of epidemic
      keratoconjunctivitis.

PMID- 16569861
TI  - Screen for inhibitors of the coupled transglycosylase-transpeptidase of
      peptidoglycan biosynthesis in Escherichia coli.
AB  - Class A high-molecular-weight penicillin-binding protein 1a (PBP1a) and PBP1b of
      Escherichia coli have both transglycosylase (TG) and transpeptidase (TP)
      activity. These enzymes are difficult to assay, since their substrates are
      difficult to prepare. We show the activity of PBP1a or PBP1b can be measured in
      membranes by cloning the PBP into an E. coli ponB::Spcr strain. Using this assay,
      we show that PBP1a is approximately 10-fold more sensitive to penicillin than
      PBP1b and that the 50% inhibitory concentration (IC50) of moenomycin, a TG
      inhibitor, is approximately 10-fold higher in the PBP transformants than in wild
      type membranes; this increase in IC50 in transformants can be used to test the
      specificity of test compounds for inhibition of the TG. Alternatively, the
      coupled TG-TP activity of PBP1b can be directly measured in a two-step microplate
      assay. In the first step, radiolabeled lipid II, the TG substrate, was made in
      membranes of the E. coli ponB::Spcr strain by incubation with the peptidoglycan
      sugar precursors. In the second step, the TG-TP activity was assayed by adding a
      source of PBP1b to the membranes. The coupled TG-TP activity converts lipid II to
      cross-linked peptidoglycan, which was specifically captured by wheat germ
      agglutinin-coated scintillation proximity beads in the presence of 0.2% Sarkosyl
      (B. Chandrakala et al., Antimicrob. Agents Chemother. 48:30-40, 2004). The TG-TP
      assay was inhibited by penicillin and moenomycin as expected. Surprisingly,
      tunicamycin and nisin also inhibited the assay, and paper chromatography analysis
      revealed that both inhibited the transglycosylase. The assay can be used to
      screen for novel antibacterial agents.

PMID- 16569863
TI  - Genetic structures at the origin of acquisition and expression of the carbapenem
      hydrolyzing oxacillinase gene blaOXA-58 in Acinetobacter baumannii.
AB  - Genetic structures surrounding the carbapenem-hydrolyzing oxacillinase gene
      blaOXA-58 were characterized in a series of OXA-58-positive Acinetobacter
      baumannii strains isolated from different countries. We showed that in most of
      the cases, acquisitions of the blaOXA-58-containing overall structure, including
      insertion sequence elements, may be likely the results of recombination events.
      In type strain A. baumannii MAD, the genetic structure surrounding the blaOXA-58
      gene was bracketed by two 27-bp repeated sequences. The isolation of a clonally
      related OXA-58-negative A. baumannii isolate that possessed the same plasmid
      backbone as A. baumannii MAD but lacked this genetic structure indicated that the
      mechanism of acquisition could be reversible. Parts of the structure identified
      in A. baumannii MAD were conserved in other blaOXA-58-positive isolates from
      various European countries. Primer extension experiments showed that blaOXA-58
      expression was related to promoter sequences brought by different insertion
      sequence elements, such as an ISAba3-like element, ISAba1, ISAba2, and IS18. This
      work identified novel structures at the origin of acquisition and expression of a
      carbapenem-hydrolyzing beta-lactamase identified in non-clonally related A.
      baumannii isolates.

PMID- 16569862
TI  - Human beta-defensin 2 induces a vigorous cytokine response in peripheral blood
      mononuclear cells.
AB  - beta-Defensins are a family of small cationic peptides involved in the innate
      response to microbial infection. Although their role in microbial killing is well
      established, the mechanisms through which this occurs remain largely undefined.
      Here, using protein array technology, we describe a role for human beta-defensins
      in the induction of an inflammatory cytokine response by human peripheral blood
      mononuclear cells (PBMCs). Human beta-defensins 1, 2, and 3 were examined for
      induction of an array of cytokines and chemokines. Some cytokines, such as
      interleukin 8 (IL-8) and monocyte chemoattractant protein 1, were up-regulated by
      all three defensins, while others, such as IL-6 and IL-10, were induced more
      selectively. It was notable that each defensin induced a unique pattern of
      cytokines. This report documents, for the first time, an analysis of the
      composite cytokine response of human PBMCs to beta-defensins. The induction or up
      regulation of a number of cytokines involved in the adaptive immune response
      suggests a possible role for these defensins in linking innate and acquired
      immunity.

PMID- 16569864
TI  - Insights into in vivo activities of lantibiotics from gallidermin and epidermin
      mode-of-action studies.
AB  - The activity of lanthionine-containing peptide antibiotics (lantibiotics) is
      based on different killing mechanisms which may be combined in one molecule. The
      prototype lantibiotic nisin inhibits peptidoglycan synthesis and forms pores
      through specific interaction with the cell wall precursor lipid II. Gallidermin
      and epidermin possess the same putative lipid II binding motif as nisin; however,
      both peptides are considerably shorter (22 amino acids, compared to 34 in nisin).
      We demonstrate that in model membranes, lipid II-mediated pore formation by
      gallidermin depends on membrane thickness. With intact cells, pore formation was
      less pronounced than for nisin and occurred only in some strains. In Lactococcus
      lactis subsp. cremoris HP, gallidermin was not able to release K+, and a mutant
      peptide, [A12L]gallidermin, in which the ability to form pores was disrupted, was
      as potent as wild-type gallidermin, indicating that pore formation does not
      contribute to killing. In contrast, nisin rapidly formed pores in the L. lactis
      strain; however, it was approximately 10-fold less effective in killing. The
      superior activity of gallidermin in a cell wall biosynthesis assay may help to
      explain this high potency. Generally, it appears that the multiple activities of
      lantibiotics combine differently for individual target strains.

PMID- 16569865
TI  - Interaction of pleuromutilin derivatives with the ribosomal peptidyl transferase
      center.
AB  - Tiamulin is a pleuromutilin antibiotic that is used in veterinary medicine. The
      recently published crystal structure of a tiamulin-50S ribosomal subunit complex
      provides detailed information about how this drug targets the peptidyl
      transferase center of the ribosome. To promote rational design of pleuromutilin
      based drugs, the binding of the antibiotic pleuromutilin and three semisynthetic
      derivatives with different side chain extensions has been investigated using
      chemical footprinting. The nucleotides A2058, A2059, G2505, and U2506 are
      affected in all of the footprints, suggesting that the drugs are similarly
      anchored in the binding pocket by the common tricyclic mutilin core. However,
      varying effects are observed at U2584 and U2585, indicating that the side chain
      extensions adopt distinct conformations within the cavity and thereby affect the
      rRNA conformation differently. An Escherichia coli L3 mutant strain is resistant
      to tiamulin and pleuromutilin, but not valnemulin, implying that valnemulin is
      better able to withstand an altered rRNA binding surface around the mutilin core.
      This is likely due to additional interactions made between the valnemulin side
      chain extension and the rRNA binding site. The data suggest that pleuromutilin
      drugs with enhanced antimicrobial activity may be obtained by maximizing the
      number of interactions between the side chain moiety and the peptidyl transferase
      cavity.

PMID- 16569866
TI  - Effect of farnesol on Staphylococcus aureus biofilm formation and antimicrobial
      susceptibility.
AB  - Staphylococcus aureus is among the leading pathogens causing bloodstream
      infections able to form biofilms on host tissue and indwelling medical devices
      and to persist and cause disease. Infections caused by S. aureus are becoming
      more difficult to treat because of increasing resistance to antibiotics. In a
      biofilm environment particularly, microbes exhibit enhanced resistance to
      antimicrobial agents. Recently, farnesol was described as a quorum-sensing
      molecule with possible antimicrobial properties. In this study, the effect of
      farnesol on methicillin-resistant and -susceptible strains of S. aureus was
      investigated. With viability assays, biofilm formation assessment, and ethidium
      bromide uptake testing, farnesol was shown to inhibit biofilm formation and
      compromise cell membrane integrity. The ability of farnesol to sensitize S.
      aureus to antimicrobials was assessed by agar disk diffusion and broth
      microdilution methods. For both strains of staphylococci, farnesol was only able
      to reverse resistance at a high concentration (150 microM). However, it was very
      successful at enhancing the antimicrobial efficacy of all of the antibiotics to
      which the strains were somewhat susceptible. Therefore, synergy testing of
      farnesol and gentamicin was performed with static biofilms exposed to various
      concentrations of both agents. Plate counts of harvested biofilm cells at 0, 4,
      and 24 h posttreatment indicated that the combined effect of gentamicin at 2.5
      times the MIC and farnesol at 100 microM (22 microg/ml) was able to reduce
      bacterial populations by more than 2 log units, demonstrating synergy between the
      two antimicrobial agents. This observed sensitization of resistant strains to
      antimicrobials and the observed synergistic effect with gentamicin indicate a
      potential application for farnesol as an adjuvant therapeutic agent for the
      prevention of biofilm-related infections and promotion of drug resistance
      reversal.

PMID- 16569868
TI  - Adding selectivity to antimicrobial peptides: rational design of a multidomain
      peptide against Pseudomonas spp.
AB  - Currently available antimicrobials exhibit broad killing with regard to bacterial
      genera and species. Indiscriminate killing of microbes by these conventional
      antibiotics can disrupt the ecological balance of the indigenous microbial flora,
      often resulting in negative clinical consequences. Species-specific
      antimicrobials capable of precisely targeting pathogenic bacteria without
      damaging benign microorganisms provide a means of avoiding this problem. In this
      communication, we report the successful creation of the first synthetic, target
      specific antimicrobial peptide, G10KHc, via addition of a rationally designed
      Pseudomonas-specific targeting moiety (KH) to a generally killing peptide
      (novispirin G10). The resulting chimeric peptide showed enhanced bactericidal
      activity and faster killing kinetics against Pseudomonas spp. than G10 alone. The
      enhanced killing activities are due to increased binding and penetration of the
      outer membrane of Pseudomonas sp. cells. These properties were not observed in
      tests of untargeted bacterial species, and this specificity allowed G10KHc to
      selectively eliminate Pseudomonas spp. from mixed cultures. This work lays a
      foundation for generating target-specific "smart" antimicrobials to complement
      currently available conventional antibiotics.

PMID- 16569867
TI  - Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus
      infection.
AB  - Influenza is a highly infectious disease characterized by recurrent annual
      epidemics and unpredictable major worldwide pandemics. Rapid spread of the highly
      pathogenic avian H5N1 strain and escalating human infections by the virus have
      set off the alarm for a global pandemic. To provide an urgently needed
      alternative treatment modality for influenza, we have generated a recombinant
      fusion protein composed of a sialidase catalytic domain derived from Actinomyces
      viscosus fused with a cell surface-anchoring sequence. The sialidase fusion
      protein is to be applied topically as an inhalant to remove the influenza viral
      receptors, sialic acids, from the airway epithelium. We demonstrate that a
      sialidase fusion construct, DAS181, effectively cleaves sialic acid receptors
      used by both human and avian influenza viruses. The treatment provides long
      lasting effect and is nontoxic to the cells. DAS181 demonstrated potent antiviral
      and cell protective efficacies against a panel of laboratory strains and clinical
      isolates of IFV A and IFV B, with virus replication inhibition 50% effective
      concentrations in the range of 0.04 to 0.9 nM. Mouse and ferret studies confirmed
      significant in vivo efficacy of the sialidase fusion in both prophylactic and
      treatment modes.

PMID- 16569869
TI  - Binding of neomycin-class aminoglycoside antibiotics to mutant ribosomes with
      alterations in the A site of 16S rRNA.
AB  - Aminoglycoside antibiotics that bind to the aminoacyl-tRNA site (A site) of the
      ribosome are composed of a common neamine core in which a glycopyranosyl ring is
      attached to position 4 of a 2-deoxystreptamine moiety. The core is further
      substituted by one (ribostamycin), two (neomycin and paromomycin), or three
      (lividomycin A) additional sugars attached to position 5 of the 2
      deoxystreptamine. To study the role of rings III, IV, and V in aminoglycoside
      binding, we used isogenic Mycobacterium smegmatis DeltarrnB mutants carrying
      homogeneous populations of mutant ribosomes with alterations in the 16S rRNA A
      site. MICs were determined to investigate drug-ribosome interactions, and the
      results were compared with that of the previously published crystal structure of
      paromomycin bound to the ribosomal A site. Our analysis demonstrates that the
      stacking interaction between ring I and G1491 is largely sequence independent,
      that rings III and IV each increase the strength of drug binding to the ribosome,
      that ring IV of the 6'-NH3+ aminoglycosides compensates for loss of interactions
      between ring II and U1495 and between ring III and G1491, that the
      aminoglycosides rely on pseudo-base pairing between ring I and A1408 for binding
      independently of the number of sugar rings attached to the neamine core, that
      addition of ring V to the 6'-OH 4,5-aminoglycoside paromomycin does not alter the
      mode of binding, and that alteration of the U1406.U1495 wobble base pair to the
      Watson-Crick interaction pair 1406C-1495G yields ribosomal drug susceptibilities
      to 4,5-aminoglycosides comparable to those seen with the wild-type A site.

PMID- 16569871
TI  - Multidimensional volumetric imaging of pulmonary infiltrates for measuring
      therapeutic response to antifungal therapy in experimental invasive pulmonary
      aspergillosis.
AB  - Pulmonary infiltrates in neutropenic hosts with invasive pulmonary aspergillosis
      are caused by vascular invasion, hemorrhagic infarction, and tissue necrosis.
      Monitoring the dynamics of pulmonary infiltrates of invasive aspergillosis is an
      important tool for assessing response to antifungal therapy. We, therefore,
      introduced a multidimensional volumetric imaging (MDVI) method for analysis of
      the response of the volume of pulmonary infiltrates over time to antifungal
      therapy in experimental invasive pulmonary aspergillosis (IPA) in persistently
      neutropenic rabbits. We developed a semiautomatic method to measure the volume of
      lung lesions, which was implemented as an extension of the MEDx visualization and
      analysis software using ultrafast computerized tomography (UFCT). Volumetric
      infiltrate measures were compared with UFCT reading, histopathological resolution
      of lesions, microbiological clearance of Aspergillus fumigatus, and galactomannan
      index (GMI). We also studied the MDVI method for consistency and reproducibility
      in comparison to UFCT. Treatment groups consisted of deoxycholate amphotericin B
      (DAMB) at 0.5 or 1 mg/kg of body weight/day and untreated controls (UC).
      Therapeutic monitoring of pulmonary infiltrates using MDVI demonstrated a
      significant decrease in the infiltrate volume in DAMB-treated rabbits in
      comparison to UC (P<or=0.001). Volumetric data by MDVI correlated with
      conventional CT pulmonary scores (r=0.83, P<or=0.001). These results correlated
      with validated biological endpoints: pulmonary infarct scores (r=0.85,
      P<or=0.001), lung weights (r=0.76, P<or=0.01), residual fungal burden (r=0.65,
      P<or=0.05), and GMI (r=0.78, P<or=0.01). MDVI correlated with key biological
      markers, improved the objectivity of radiological assessment of therapeutic
      response to antifungal therapy, and warrants evaluation for monitoring
      therapeutic response in immunocompromised patients with invasive aspergillosis.

PMID- 16569873
TI  - The antimicrobial peptide polyphemusin localizes to the cytoplasm of Escherichia
      coli following treatment.
AB  - The horseshoe crab peptide polyphemusin I possesses high antimicrobial activity,
      but its mechanism of action is as yet not well defined. Using a biotin-labeled
      polyphemusin I analogue and confocal fluorescence microscopy, we showed that the
      peptide accumulates in the cytoplasm of wild-type Escherichia coli within 30 min
      after addition without causing substantial membrane damage.

PMID- 16569872
TI  - Substrate envelope and drug resistance: crystal structure of RO1 in complex with
      wild-type human immunodeficiency virus type 1 protease.
AB  - In our previous crystallographic studies of human immunodeficiency virus type 1
      (HIV-1) protease-substrate complexes, we described a conserved "envelope" that
      appears to be important for substrate recognition and the selection of drug
      resistant mutations. In this study, the complex of HIV-1 protease with the
      inhibitor RO1 was determined and comparison with the substrate envelope provides
      a rationale for mutational patterns.

PMID- 16569870
TI  - Preclinical evaluation of synthetic -2 RANTES as a candidate vaginal microbicide
      to target CCR5.
AB  - A potential strategy that can be used to combat the worldwide AIDS epidemic is
      the development of a vaginal microbicide that prevents the sexual transmission of
      human immunodeficiency virus type 1 (HIV-1). Certain CC chemokines, including
      RANTES, MIP-1alpha, and MIP-1beta, might facilitate the development of such
      microbicides since they potently suppress HIV-1 infection by binding to CCR5, the
      viral coreceptor used by most sexually transmitted strains of HIV-1 to enter host
      cells. In this study, we evaluated whether a CCR5-specific fragment of RANTES
      that lacks two N-terminal residues (-2 RANTES) and possesses especially potent
      HIV-1 suppressive activity has toxicity profiles conducive to the advancement of
      testing in candidate microbicide formulations. Analyses were carried out with a
      synthetic version of the chemokine, which was formulated with either Novasomes
      7474, a nonphospholipid liposome, or methylcellulose gel. Dialysis studies
      demonstrated that the formulated -2 RANTES was released from both vehicles and
      retained anti-HIV-1 activity. Preclinical toxicity studies carried out with Swiss
      Webster mouse and New Zealand White rabbit vaginal irritation models demonstrated
      minimal inflammation and minimal adverse changes in cervicovaginal tissue
      integrity after short-term (10 min) and long-term (24 h) exposure to formulations
      containing up to 1 mg/ml of -2 RANTES. Similarly, no toxicity was observed with
      formulations of bioactive murine RANTES in the Swiss Webster mouse vaginal
      irritation model. Overall, these preclinical studies suggest that -2 RANTES is
      suitable for further testing as a candidate anti-HIV-1 microbicide.

PMID- 16569874
TI  - In vivo selection of fluoroquinolone-resistant Escherichia coli isolates
      expressing plasmid-mediated quinolone resistance and expanded-spectrum beta
      lactamase.
AB  - A ciprofloxacin-resistant Escherichia coli isolate, isolate 1B, was obtained from
      a urinary specimen of a Canadian patient treated with norfloxacin for infection
      due to a ciprofloxacin-susceptible isolate, isolate 1A. Both isolates harbored a
      plasmid-encoded sul1-type integron with qnrA1 and blaVEB-1 genes. Isolate 1B had
      amino acid substitutions in gyrase and topoisomerase.

PMID- 16569875
TI  - Microflora changes with norfloxacin and pivmecillinam in women with recurrent
      urinary tract infection.
AB  - Similar changes in the periurethral and vaginal microflora were observed in 19
      women with recurrent urinary tract infection following treatment with norfloxacin
      (NOR) or pivmecillinam (PIV). Escherichia coli strains were suppressed by both
      treatments. Staphylococcus spp. and enterococci colony counts increased following
      PIV treatment in the periurethral flora but remained stable with NOR.

PMID- 16569876
TI  - Plasmodium falciparum in vitro susceptibility to antimalarial drugs in Casamance
      (southwestern Senegal) during the first 5 years of routine use of artesunate
      amodiaquine.
AB  - We have monitored the in vitro sensitivities of Plasmodium falciparum isolates
      predeployment and during the deployment of artesunate plus amodiaquine treatment
      in Mlomp, Casamance (southwestern Senegal) during 2000 to 2004. Parasites
      remained susceptible to both drugs. Chloroquine resistance levels were high but
      stable. Quinine continues to be effective.

PMID- 16569877
TI  - Antimalarial activity of a synthetic endoperoxide (RBx-11160/OZ277) against
      Plasmodium falciparum isolates from Gabon.
AB  - OZ277 is a newly developed, fully synthetic endoperoxide antimalarial that we
      tested against field isolates from Gabon. A comparison of activities of OZ277
      with artesunate, mefloquine, and chloroquine showed OZ277 to be highly active
      against all parasite isolates. Artesunate and mefloquine also showed potent
      antiparasitic activity, but all isolates were chloroquine resistant.

PMID- 16569878
TI  - Gatifloxacin resistance and mutations in gyra after unsuccessful Helicobacter
      pylori eradication in Japan.
AB  - A high resistance rate (47.9%) to gatifloxacin (GAT; 8-methoxy fluoroquinolone)
      in Helicobacter pylori (H. pylori) strains from 48 Japanese patients is observed
      after unsuccessful H. pylori eradication. A significant association between MICs
      for GAT equal to or above 1 microg/ml and mutations of the gyrA gene of H. pylori
      was demonstrated.

PMID- 16569879
TI  - Autolytic properties of glycopeptide-intermediate Staphylococcus aureus Mu50.
AB  - Whole-cell autolytic activity of prototypical glycopeptide-intermediate
      Staphylococcus aureus (GISA) Mu50 was reduced versus that of hetero-GISA Mu3 and
      glycopeptide-susceptible S. aureus, consistent with other GISA strains. In
      contrast, autolytic activity was relatively high in Mu50 crude cell walls and
      autolysin extracts against purified cell walls, reflecting the complexities of
      autolytic activity regulation.

PMID- 16569880
TI  - Quadruple mutations in dihydrofolate reductase of Plasmodium falciparum isolates
      from Car Nicobar Island, India.
AB  - Quadruple mutations in the Plasmodium falciparum dihydrofolate reductase (PFDHFR)
      enzyme give rise to the highest level of pyrimethamine resistance leading to
      treatment failures. We describe here the presence of these quadruple mutations in
      a majority of P. falciparum isolates from Car Nicobar (Andaman and Nicobar)
      Island, India. Isolates from the mainland, however, continue to show a prevalence
      of double PFDHFR mutations and some with triple but none with quadruple
      mutations. In conclusion, the antifolate drug pressure is very high in the
      island, which should be a cause of concern for the malaria control program in the
      country.

PMID- 16569881
TI  - Genetic basis of tetracycline and minocycline resistance in potentially probiotic
      Lactobacillus plantarum strain CCUG 43738.
AB  - The potentially probiotic strain Lactobacillus plantarum CCUG 43738, which
      displayed atypical phenotypic resistance to tetracycline (MIC, 512 microg/ml) and
      minocycline (MIC, 256 microg/ml), was found to contain a tet(S) gene located on a
      plasmid of approximately 14 kb. Plasmid curing with novobiocin eliminated this
      plasmid and restored the tetracycline-susceptible phenotype of the host strain.

PMID- 16569882
TI  - In vivo efficacy of aerosolized nanostructured itraconazole formulations for
      prevention of invasive pulmonary aspergillosis.
AB  - Aerosolized evaporative precipitation into aqueous solution and spray freezing
      into liquid nanostructured formulations of itraconazole as prophylaxis
      significantly improved survival relative to commercial itraconazole oral solution
      and the control in a murine model of invasive pulmonary aspergillosis.
      Aerosolized administration of nanostructured formulations also achieved high lung
      tissue concentrations while limiting systemic exposure.

PMID- 16569883
TI  - In vitro activity of tigecycline against Burkholderia pseudomallei and
      Burkholderia thailandensis.
AB  - Investigation of the in vitro activity of tigecycline against Burkholderia
      pseudomallei and Burkholderia thailandensis revealed that the inhibition zone
      diameters of tigecycline against all isolates were >or=20 mm and that the MIC50
      values were 0.5 and 1 microg/ml and the MIC90 values were 2 and 1.5 microg/ml for
      B. pseudomallei and B. thailandensis, respectively.

PMID- 16569884
TI  - Bactericidal activities of R207910 and other newer antimicrobial agents against
      Mycobacterium leprae in mice.
AB  - As measured by a proportional bactericidal technique in the mouse footpad system,
      the bactericidal activity against Mycobacterium leprae of R207910 was equal to
      that of rifapentine, rifampin, or moxifloxacin and significantly greater than
      those of minocycline, PA-824, and linezolid. These data suggest that R207910 may
      play an important role in treatment of leprosy.

PMID- 16569885
TI  - Prevalence of first-step mutants among levofloxacin-susceptible invasive isolates
      of Streptococcus pneumoniae in the United States.
AB  - By use of a PCR-restriction fragment length polymorphism assay, we screened 496
      levofloxacin-susceptible invasive pneumococcal strains (MIC<or=2 mg/liter) for
      quinolone resistance-determining region mutations known to confer fluoroquinolone
      resistance. Among those with a levofloxacin MIC of 2 mg/liter, 16.2% of isolates
      recovered from nursing home residents and 6.4% from non-nursing home residents
      had first-step mutations.

PMID- 16569886
TI  - Ether lipid ester derivatives of cidofovir inhibit polyomavirus BK replication in
      vitro.
AB  - Polyomavirus BK is a significant pathogen in transplant recipients, but no
      effective antiviral therapy is available. We show that cidofovir can inhibit BK
      virus replication in vitro. Esterification of cidofovir with hexadecyloxypropyl,
      octadecyloxyethyl, and oleyloxyethyl groups results in up to a 3-log lowering of
      the 50% effective concentration and an increased selectivity index.

PMID- 16569887
TI  - Sequential or combination antifungal therapy with voriconazole and liposomal
      amphotericin B in a Guinea pig model of invasive aspergillosis.
AB  - We evaluated combinations of voriconazole (VRC) and liposomal amphotericin B (L
      AMB) in a guinea pig invasive aspergillosis model. Simultaneous VRC and L-AMB was
      most effective, although VRC monotherapy was also effective. These regimens as
      well as sequential L-AMB followed by VRC were more effective than L-AMB alone or
      VRC followed by L-AMB.

PMID- 16569889
TI  - Immunotherapy with tacrolimus (FK506) does not select for resistance to
      calcineurin inhibitors in Candida albicans isolates from liver transplant
      patients.
AB  - In Candida albicans, calcineurin mediates tolerance to azole antifungal drugs,
      survival in serum, and virulence. In this study, we examined 24 Candida isolates
      from liver transplant recipients receiving a calcineurin inhibitor as a component
      of their immunosuppressive therapy. We were unable to detect a difference in
      susceptibility to calcineurin inhibitors in combination with fluconazole, serum,
      or calcium in these isolates.

PMID- 16569890
TI  - Ritonavir increases plasma amprenavir (APV) exposure to a similar extent when
      coadministered with either fosamprenavir or APV.
AB  - To compare the effect of ritonavir on plasma amprenavir pharmacokinetics, healthy
      adults received either fosamprenavir (700 mg twice a day [BID]) or amprenavir
      (600 mg BID) alone and in combination with ritonavir (100 mg BID). Ritonavir
      increased plasma amprenavir pharmacokinetic parameters to a similar extent when
      coadministered with either fosamprenavir or amprenavir.

PMID- 16569888
TI  - Voriconazole therapeutic drug monitoring.
AB  - We report on 28 patients who underwent voriconazole monitoring because of disease
      progression or toxicity. A relationship (P<0.025) between disease progression and
      drug concentration was detected. Favorable responses were observed in 10/10
      patients with concentrations above 2.05 microg/ml, while disease progressed in
      44% (n=18) of patients with concentrations below 2.05 microg/ml.

PMID- 16569891
TI  - Induction of daptomycin heterogeneous susceptibility in Staphylococcus aureus by
      exposure to vancomycin.
AB  - We studied vancomycin and daptomycin susceptibility in methicillin-resistant
      Staphylococcus aureus from patients exposed to vancomycin, glycopeptide
      intermediate S. aureus, and S. aureus passaged in vancomycin-containing medium. A
      correlation between vancomycin and daptomycin heteroresistance was noted in some
      strains, suggesting that exposure of S. aureus to vancomycin may affect
      susceptibility to daptomycin.

PMID- 16569892
TI  - New approach for high-throughput screening of drug activity on Plasmodium liver
      stages.
AB  - Plasmodium liver stages represent potential targets for antimalarial prophylactic
      drugs. Nevertheless, there is a lack of molecules active on these stages. We have
      now developed a new approach for the high-throughput screening of drug activity
      on Plasmodium liver stages in vitro, based on an infrared fluorescence scanning
      system. This method allowed us to count automatically and rapidly Plasmodium
      infected hepatocytes, using different hepatic cells and different Plasmodium
      species, including Plasmodium falciparum. This new technique is well adapted for
      high-throughput drug screening and should facilitate the identification of new
      antimalarial compounds active on Plasmodium liver stages.

PMID- 16569893
TI  - Variability in the region downstream of the blaCMY-2 beta-lactamase gene in
      Escherichia coli and Salmonella enterica plasmids.
AB  - We used sequencing and PCR mapping to investigate the regions flanking the blaCMY
      2 beta-lactamase gene carried by plasmids from Escherichia coli and Salmonella
      enterica. Results revealed genetic heterogeneity in the region downstream from
      blaCMY-2 and identified a putative transposable element bearing blaCMY-2.

PMID- 16569894
TI  - New real-time PCR assay using locked nucleic acid probes to assess prevalence of
      ParC mutations in fluoroquinolone-susceptible Streptococcus pneumoniae isolates
      from France.
AB  - A real-time PCR assay with locked nucleic acid probes was developed to screen
      mutations at codons 79 and 83 of the Streptococcus pneumoniae parC gene. Only
      silent mutations were detected among 236 French invasive fluoroquinolone
      susceptible strains. This test could be useful for some high-risk patients or in
      national surveys.

PMID- 16569896
TI  - Large conjugative plasmids from clinical strains of Salmonella enterica serovar
      virchow contain a class 2 integron in addition to class 1 integrons and several
      non-integron-associated drug resistance determinants.
AB  - Two large conjugative resistance (R) plasmids from clinical strains of Salmonella
      enterica serovar Virchow carried a class 2 integron with the 5' conserved
      sequence (5'CS)-dfrA1-sat1-aadA1-3'CS gene array, which is associated with
      defective Tn7 transposons. In addition, each contained a different class 1
      integron (with 5'CS-aadA1-3'CS or 5'CS-sat-smr-aadA1-3'CS gene arrays) linked to
      Tn21-Tn9 sequences, and several non-integron-associated R determinants. An intact
      copy of Tn7 (including the class 2 integron) was present in the chromosome of
      each strain.

PMID- 16569897
TI  - First report of extended-spectrum-beta-lactamase-producing Salmonella enterica
      isolates in Ireland.

PMID- 16569895
TI  - Good clinical outcomes but high rates of adverse reactions during linezolid
      therapy for serious infections: a proposed protocol for monitoring therapy in
      complex patients.
AB  - We assessed the toxicity and clinical outcomes associated with linezolid therapy
      (mean duration, 29+/-28 days; range, 8 to 185 days) in 44 patients with serious
      gram-positive infections. Although a clinical cure was achieved in 73% of the
      cases, 28/44 (64%) had adverse reactions (thrombocytopenia, n=13; anemia, n=7;
      gastrointestinal, n=12; peripheral neuropathy, n=1; serotonin syndrome, n=1),
      such that a systematic monitoring protocol was developed.

PMID- 16569898
TI  - First isolation of blaIMI-2 in an Enterobacter cloacae clinical isolate from
      China.

PMID- 16569899
TI  - Class 1 Integrons in Salmonella Strains causing traveler's diarrhea.

PMID- 16569903
TI  - Pandemic influenza: are Europe's institutions prepared?

PMID- 16569904
TI  - Commentary: Europe's preparedness for an influenza pandemic.

PMID- 16569906
TI  - Lower utilization of primary, specialty and preventive care services by
      individuals residing with persons in poor health.
AB  - BACKGROUND: Since household time and financial resources for health care are
      primarily spent for those household members with the most urgent health needs,
      individuals residing with persons in poor health may be at risk of underusing
      health-care services. We examined whether these individuals had a lower use of
      primary, specialty and preventive care than those who did not reside with persons
      in poor health. METHODS: Data collected in 2000 from a representative sample of
      8,210 French individuals aged 18 years and older from 3,810 households were
      analysed with logistic regression models adjusted for health, demographic and
      socioeconomic variables. RESULTS: We found that individuals residing with one
      other survey respondent had a higher risk of not using primary care, specialty
      care and preventive care in the 12 months preceding the study when the health
      status of the other survey respondent was poorer (fair or alternatively poor
      versus good). Furthermore, individuals residing with two other survey respondents
      had a higher risk of not using primary care, specialty care and preventive care
      in the 12 months preceding the study when they resided with a higher number of
      respondents in fair or poor health (one or alternatively two versus zero).
      CONCLUSION: The lower use of health services by individuals residing with persons
      in poor health may signal a need for health practitioners to broaden the scope of
      care beyond their patients, and for policy makers to consider the long-term
      impact of this situation on the health-care system.

PMID- 16569907
TI  - Showing leads to doing: graphic cigarette warning labels are an effective public
      health policy.

PMID- 16569910
TI  - Transport of vitamin E by differentiated Caco-2 cells.
AB  - In hepatocytes, vitamin E is secreted via the efflux pathway and is believed to
      associate with apolipoprotein B (apoB)-lipoproteins extracellularly. The
      molecular mechanisms involved in the uptake, intracellular trafficking, and
      secretion of dietary vitamin E by the intestinal cells are unknown. We observed
      that low concentrations of Tween-40 were better for the solubilization and
      delivery of vitamin E to differentiated Caco-2 cells, whereas high concentrations
      of Tween-40 and sera inhibited this uptake. Vitamin E uptake was initially rapid
      and then reached saturation. Subcellular localization revealed that vitamin E
      primarily accumulated in microsomal membranes. Oleic acid (OA) treatment, which
      induces chylomicron assembly and secretion, decreased microsomal membrane-bound
      vitamin E in a time-dependent manner. To study secretion, differentiated Caco-2
      cells were pulse-labeled with vitamin E and chased in the presence and absence of
      OA. In the absence of OA, vitamin E was associated with intestinal high density
      lipoprotein (I-HDL), whereas OA-treated cells secreted vitamin E with I-HDL and
      chylomicrons. No extracellular transfer of vitamin E between these lipoproteins
      was observed. Glyburide, an antagonist of ABCA1, partially inhibited its
      secretion with I-HDL, whereas plasma HDL increased vitamin E efflux. An
      antagonist of microsomal triglyceride transfer protein, brefeldin A, and monensin
      specifically inhibited vitamin E secretion with chylomicrons. These studies
      indicate that vitamin E taken up by Caco-2 cells is stored in the microsomal
      membranes and secreted with chylomicrons and I-HDL. Transport via I-HDL might
      contribute to vitamin E absorption in patients with abetalipoproteinemia
      receiving large oral doses of the vitamin.

PMID- 16569909
TI  - Distinct modulation of angiotensin II-induced early left ventricular hypertrophic
      gene programming by dietary fat type.
AB  - Long-term dietary fatty acid intake alters the development of left ventricular
      hypertrophy, but the linking signaling pathways are unclear. We studied the role
      and underlying signaling mechanisms of dietary fat intake in the early phase of
      the hypertrophic process. Rats assigned for 4 weeks of high-oil, high-fat, or
      standard diet were subjected to angiotensin II (Ang II; 33 microg/kg/h,
      subcutaneous) or vehicle infusion for 24 h. The Ang II-induced increase in left
      ventricular mRNA levels of hypertrophy-associated genes was higher in rats fed
      the high-oil diet compared with the standard diet. Western blotting revealed
      that, in parallel with changes in gene expression, the high-oil diet increased c
      Jun N-terminal kinase phosphorylation (P < 0.001). Ang II increased p38 mitogen
      activated protein kinase (MAPK) phosphorylation in rats fed the high-fat diet (3
      fold; P < 0.01). The increase in transcription factor activator protein-1 (AP-1)
      DNA binding activity in response to Ang II was higher in rats fed the high-oil
      diet compared with those fed the standard diet (P < 0.001). Ang II downregulated
      inducible nitric oxide synthase mRNA levels in fatty acid-supplemented groups
      compared with the standard diet group. These results show that dietary fat type
      modulates the early activation of hypertrophic genes in pressure-overloaded
      myocardium involving the distinct activation of AP-1 and MAPK signal transduction
      pathways.

PMID- 16569911
TI  - Biomolecular interactions by Surface Plasmon Resonance technology.
AB  - The Surface Plasmon Resonance (SPR) technique makes it possible to measure
      biomolecular interactions in real-time with a high degree of sensitivity and
      without the need of label. The information obtained is both qualitative and
      quantitative and it is possible to obtain the kinetic parameters of the
      interaction. This new technology has been used to study a diverse set of
      interaction partners of biological interest, such as protein-protein, protein
      lipids, protein- nucleic acids or protein and low molecular weight molecules such
      as drugs, substrates and cofactors. In addition to basic biomedical research, the
      SPR biosensor has recently been used in food analysis, proteomics, immunogenicity
      and drug discovery.

PMID- 16569912
TI  - Mass spectrometry for protein identification and the study of post translational
      modifications.
AB  - Mass spectrometry is a powerful tool for the structural characterization of
      proteins. The development of a large number of analytical strategies based on
      different mass spectrometric techniques has established mass spectrometry as an
      indispensable technology to interpret the information encoded in the genome. This
      manuscript intends to provide a rapid view of principles and instrumentation in
      mass spectrometry-based proteomics, together with a description of the basic
      features and limits of the analysis of post translational modifications by mass
      spectrometry. The application of one of the available mass spectrometry
      technologies for protein identification to a multi-protein complex isolated in a
      specific functional context is reported. The identification of a phosphorylation
      site on a single, purified protein is also illustrated as an example.

PMID- 16569913
TI  - Proteomics approaches to study the redox state of cysteine-containing proteins.
AB  - All the proteins synthesized in a cell undergo several post-translational
      modifications that are essential in their functional regulation. Among these, the
      change of the redox state of Cysteine residues is assuming a great interest: this
      modification in fact, represents a very dynamic and regulated balance. There are
      several reversible oxidative events that can occur and that are difficult to
      detect. In this work we describe a methodology useful to recognize and to select
      Cysteines containing proteins on the basis of their redox state. The strategy is
      based on the selective labeling of the interested proteins and allows their
      visualization by Western Blot, enrichment by affinity chromatography and finally
      the identification of the protein and of the modified Cysteine residues by mass
      spectrometry. This methodology can be used in proteomic studies to recognize
      redox-sensitive Cysteine containing proteins and nitric oxide targets.

PMID- 16569914
TI  - Differential proteomic analysis in the study of prokaryotes stress resistance.
AB  - Proteomic technologies are powerful tools to study the physiological response of
      bacteria to various environmental stress conditions. Complex protein toolkits
      coordinated by regulatory networks have evolved to accommodate bacterial survival
      under several stressing conditions, such as varying temperature or pH, and
      changes in nutrient availability. This manuscript provides an overview of the
      major achievements obtained by 2D gel based and non-gel based proteomic
      approaches for the study of adaptive response in bacteria. As an example, a study
      carried out on Streptococcus thermophilus response to various stresses is here
      reported. In this investigation, we used combined proteomic strategies to define
      proteomic maps useful to highlight protein profile variations following
      environmental challenges.

PMID- 16569915
TI  - Functional genomics, new tools in malaria research.
AB  - The mosquito-transmitted unicellular parasite Plasmodium falciparum, the agent of
      malaria disease, still causes more than one million deaths every year in the
      tropical and subtropical areas of the world. New intervention strategies are
      needed to contrast the insurgence of resistance to effective drugs and
      insecticides. The complete annotated genomes of the human parasite P. falciparum
      and the rodent model P. yoelii is now available thus providing a prediction of
      their possible gene products. This makes feasible the application of functional
      genomics to malaria research with the final goal of providing a complete survey
      of Plasmodium life cycle. Genome-wide approaches to the study of transcriptome or
      proteome were successfully applied to malaria parasite with the promise for new
      drug and vaccine candidates in the next future.

PMID- 16569917
TI  - Delta9 THC content in illicit cannabis products over the period 1997-2004 (first
      four months).
AB  - The aim of this study is to determine delta 9 tetrahydrocannabinol (delta9 THC)
      content in 5227 seizures of cannabis products over the period 1997-2004 (first
      four months). The products were seized in Modena country (Italy). The samples
      were classified as marijuana and hashish and divided into subgroups. The
      following results show an increase in the potency (concentration of delta9 THC)
      of these products.

PMID- 16569916
TI  - Homo sapiens proteomics: clinical perspectives.
AB  - The complete human genome sequencing project opened the route to a new holistic
      scientific movement, characterised by the investigation of the functional
      elements of our genetic heredity mainly in respect to multifactorial diseases
      such as cancer, diabetes, dementias, etc. The clinical proteomics tries to
      highlight the relationships between the main molecular physiological effectors,
      proteins, with defined physiopathological conditions. The development of a new
      generation of mass spectrometers is deeply changing the technologies employed in
      these investigations, enabling direct quantitative analysis of clinical samples
      such as, blood, urine, saliva and biopsy samples. In this manuscript we introduce
      and discuss the main phases of these investigations and their possible follow up
      in diagnostic and functional studies.

PMID- 16569918
TI  - Selected persistent organic pollutants (POPs) in the Italian environment.
AB  - The ratification of the Stockholm Convention on Persistent Organic Pollutants is
      a departure point for several considerations on their presence in environmental
      matrices. In this paper, the Italian situation is presented with emphasis on the
      most toxic compounds--chemicals with dioxin-like toxic action, and the activity
      in the area of interest of the Istituto Superiore di Sanita. Biotic, as well as
      abiotic matrices have been taken in consideration and, where possible, a
      comparation between their contamination levels with the levels reported on
      similar matrices by other European countries has been reported.

PMID- 16569919
TI  - Quality assurance in radiotherapy. How to improve the effectiveness and
      completeness of an electronic patient's chart.
AB  - A checking form was introduced in order to test the completeness of electronic
      and paper patient's charts in a radiotherapy department which had introduced
      record-and-verify system (RVS) and to improve tha staff performance. The chosen
      items for the electronic chart were 9 and 5 for paper chart. 223 patients were
      reviewed in two phases. The data analysis was based on a scoring method,
      attributing a positive score (+1) to the operator's good behaviour, a negative
      score (-1) to the lack of data input and a neutral score (0) to the inapplicable
      situation. The average global score increased from 0.4 to 0.7: in A (lowest
      complexity) category from 0.37 to 0.64, in B category from 0.4 to 0.89, in C
      category from 0.48 to 0.61.

PMID- 16569920
TI  - [Parental evaluation of child and adolescent mental health services: a
      multicentric study].
AB  - A self-completed questionnaire for routinely assessing parents' opinions on the
      quality of care in child and adolescent mental health services was developed. A
      reliability study was performed, and the questionnaire was then introduced in the
      practice of 5 services. Parents' opinions were evaluated, and specific aspects of
      services more associated with the overall opinion were investigated. Very good
      results were observed in the reliability study. Parents had critical opinions
      about the availability of the rehabilitative equipment, emergency management, and
      linkage among different types of services. The judgement about health outcomes
      was the most important predictor of the overall opinion on the quality of
      services. Because of its user-friendliness, the questionnaire may be particularly
      suitable for routine use.

PMID- 16569921
TI  - [The study of the new diagnoses of HIV infection in Italy through regional
      surveillance systems: operative characteristics and evaluation].
AB  - The information provided by HIV surveillance systems is essential for describing
      current changes in the epidemic and for identifying in a timely manner the
      geographic areas and subpopulations at greatest risk. In Italy, no national-level
      HIV surveillance system exists, and only 6 of the country's 20 regions and 3 of
      its provinces have created local systems. In April 2004 a descriptive
      investigation of these systems was conducted. The results show extreme
      variability in their sensitivity and completeness and stress the need to extend
      systems to all of Italy's regions and to standardise the methods for collecting
      and transmitting data.

PMID- 16569922
TI  - [Coeliac disease and reproduction: possible in vivo models].
AB  - Presently there are no in vivo models to study the different effects of coeliac
      disease (CD) including the increase of reproductive risks. CD is a multifactorial
      condition which requires both an exogenous element (gluten) and complex genetic
      factors; moreover, CD is associated to several endocrine, immune and reproductive
      diseases. There are no adequate in vivo models for the systemic complications of
      CD; in particular, there are no genetic knock-out models. However, models are
      available for gluten enteropathy such as Irish Setter and Balb/c and BDF1 mouse
      strains, and also for endocrine-immune diseases associated to CD such as BB rats
      and NOD mice. These models could be used to study reproductive aspects. This is
      desirable because a new model for dermatitis herpetiformis tightly associated
      with CD, that uses HLA-DQ8 transgenic NOD mice, has already been identified.

PMID- 16569923
TI  - Effect of habitual arecanut chewing on resting whole mouth salivary flow rate and
      pH.
AB  - BACKGROUND: Resting whole mouth salivary flow rate (SFR) and pH play a
      significant role in pathogenesis of various oral diseases and conditions. AIM: To
      observe the effect of habitual use of arecanut and various arecanut containing
      products (AN) on SFR and pH. DESIGN: Cross sectional. SETTING: Outpatient
      Department of Dental College. PARTICIPANTS: AN chewers and non-chewers attending
      Dental college. MEASUREMENTS: SFR and pH. VARIABLES: Type, frequency, duration
      and exposure time of AN, Smoking and Alcohol habit. MATERIALS AND METHODS:
      Subjects study was divided into chewers (n=110) and non- chewers (n=50). The SFR
      (expressed in mL/10min) and pH measured. RESULTS: The difference between the mean
      SFR for chewers and non-chewers was not statistically significant. The difference
      between mean pH of chewers and non-chewers was statistically significant.
      (P=0.02). Difference in pH was statistically significant among the different
      types of AN chewers (P=0.024). With chewing raw AN, an increase in frequency and
      exposure time increased SFR and pH respectively. In processed AN chewers,
      increase in duration and frequency of consumption increased SFR and decreased pH
      respectively. For chewers with betel quid with tobacco, increase in duration was
      significantly associated with decrease in salivary pH. CONCLUSION: SFR and pH are
      altered in AN chewers, rendering the oral mucosa vulnerable to the toxic effects
      of AN.

PMID- 16569924
TI  - Strongyloides stercoralis infestation in a patient with severe ulcerative
      colitis.
AB  - Asymptomatic infestation with Strongyloides stercoralis, common in the tropics,
      may result in potentially fatal hyperinfection during treatment with
      immunosuppressive drugs used to treat patients with severe ulcerative colitis
      (UC). Hence, importance of early recognition and treatment of this nematode in
      patients with UC before starting immunosuppressive drugs can not be
      overemphasized. We report a 23-yrs old man with UC who presented with acute
      severe attack. Since his UC did not respond to intravenous hydrocortisone over 6
      days, oral cyclosporine was started on 7th day after repeating stool microscopy,
      which revealed larvae of Strongyloides stercoralis. Duodenal aspirate also
      confirmed presence of multiple larvae. He responded to treatment for
      Strongyloides stercoralis , continuation of hydrocortisone and cyclosporine.
      Importance of early diagnosis of infestation with Strongyloides stercoralis while
      on treatment with immunosuppressive drugs for severe UC is emphasized.
      Difficulties in diagnosis and management of Strongyloides stercoralis infestation
      in patients with UC are discussed.

PMID- 16569925
TI  - Pregnancy in a patient of Glanzmann's thrombasthenia.
AB  - Glanzmann's thrombasthenia is a congenitally acquired platelet disorder with an
      autosomal recessive mode of inheritance. Though, quantitatively normal, the
      aggregation ability of platelets is reduced in this condition. Pregnancy and
      delivery are rare in these patients and have been associated with a high risk of
      severe post-partum hemorrhage. We describe a primigravida, who was diagnosed to
      have Glanzmann's thrombasthenia during adolescence. She developed secondary post
      partum hemorrhage after an elective caesarean section, which was successfully
      managed by single donor platelet transfusion.

PMID- 16569926
TI  - Chronic renal failure and electroconvulsive therapy.

PMID- 16569927
TI  - Classical mania associated with dengue infection.

PMID- 16569928
TI  - Newer insulin analogues and inhaled insulin.
AB  - Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin
      is used in the management of this condition. The development of human insulin has
      provided tighter control of glycaemia in diabetic patients. Insulin analogues
      like insulin lispro and aspart were developed to closely match its profile with
      physiological secretion. The newer additions to this armamentarium are insulin
      glulisine, insulin detemir and albulin. Insulin glulisine is a short acting
      analogue with a rapid onset of action. The antiapoptotic property, mediated
      through insulin substrate receptor-2 has a favourable protective action on beta
      cells. Insulin detemir is a long acting analogue, soluble at neutral pH, which
      reversibly binds to albumin in plasma, prolonging its action. Its lower affinity
      for insulin receptors necessitates higher doses compared to human insulin. The
      reduction in body weight is an additional advantage of detemir. A major concern
      about all newer insulin analogues is their altered mitogenic properties and
      resultant risk of carcinogenicity on long term use. Albulin is a latest addition
      of insulin analogue which is under various in vitro and in vivo studies. Inhaled
      insulin in powder form (Exubera) is recently approved by FDA and appears
      promising.

PMID- 16569929
TI  - Effects of rapid versus slow infusion of sodium bicarbonate on cerebral
      hemodynamics and oxygenation in preterm infants.
AB  - BACKGROUND: Sodium bicarbonate (NaHCO3) is often used for correction of metabolic
      acidosis in preterm infants. The effects of NaHCO3 administration on cerebral
      hemodynamics and oxygenation are not well known. Furthermore, there is no
      consensus on infusion rate of NaHCO3. OBJECTIVES: To evaluate the effects of
      rapid versus slow infusion of NaHCO3 on cerebral hemodynamics and oxygenation in
      preterm infants. METHODS: Twenty-nine preterm infants with metabolic acidosis
      were randomized into two groups (values are mean +/-SD): In group A (GA 30.5 +/-
      1.7 weeks, b.w. 1,254 +/- 425 g) NaHCO3 4.2% was injected as a bolus. In group B
      (GA 30.3 +/- 1.8 weeks, b.w. 1,179 +/- 318 g) NaHCO3 4.2% was administered over a
      30-min period. Concentration changes of oxyhemoglobin (cO2Hb) and deoxyhemoglobin
      (cHHb) were assessed using near infrared spectrophotometry. Changes in HbD (=
      cO2Hb - cHHb) represent changes in cerebral blood oxygenation and changes in ctHb
      (= cO2Hb + cHHb) reflect changes in cerebral blood volume. Cerebral blood flow
      velocity was intermittently measured using Doppler ultrasound. Longitudinal data
      analysis was performed using linear mixed models (SAS procedure MIXED), to
      account for the fact that the repeated observations in each individual were
      correlated. RESULTS: Administration of NaHCO3 resulted in an increase of cerebral
      blood volume which was more evident if NaHCO3 was injected rapidly than when
      infused slowly. HbD and cerebral blood flow velocity did not show significant
      changes in either group. CONCLUSION: To minimize fluctuations in cerebral
      hemodynamics, slow infusion of sodium bicarbonate is preferable to rapid
      injection.

PMID- 16569931
TI  - Activating transcription factor 3 is estrogen-responsive in utero and upregulated
      during sexual differentiation.
AB  - BACKGROUND/AIMS: Synthetic estrogens induce hypospadias, an anomaly of genital
      tubercle/urethral development. Activating transcription factor 3 (ATF3), which is
      estrogen-responsive in vitro, is upregulated in hypospadiac human tissue. We used
      a mouse model of steroid-dependent genital tubercle development to elucidate the
      ontogeny of ATF3 expression and the developmental response of ATF3 in vivo to
      estrogen exposure. METHODS: We used quantitative RT-PCR to assess ontogenic
      expression of ATF3 and its response to estrogen treatment in utero.
      Immunohistochemistry was used to localize the protein. RESULTS: Quantitative RT
      PCR showed that ATF3 mRNA is upregulated in all estrogen-exposed fetal genital
      tubercles compared to controls (p = 0.024), including specifically in males
      exposed in utero (p = 0.049). Additionally, its expression increases
      significantly during the period of sexual differentiation in both sexes and
      significantly correlates with female development (p = 0.004), a phenomenon that
      appears to be attributable to higher levels at birth in females. The protein
      localizes in the nucleus, as expected. CONCLUSIONS: ATF3 is estrogen-responsive
      in vivo. The response of ATF3 to estrogenic stimulation in utero at an earlier
      stage may contribute to urethral abnormalities observed in estrogen-exposed male
      fetuses, although it is likely not the only gene involved, which supports the
      general understanding that hypospadias is subject to multifactorial influences.
      ATF3 may therefore be an appropriate gene for further investigations in an
      endocrine context.

PMID- 16569930
TI  - Activation antigens during the proliferative and secretory phases of endometrium
      and early-pregnancy decidua.
AB  - BACKGROUND: Clarifying the normal distribution of activation antigens will
      contribute to database construction studies of monoclonal-antibody-based
      therapies in endometrial disorders. METHODS: In this study, endometrial tissue
      samples obtained during proliferative and secretory phases and decidual samples
      of early pregnancies were immunostained by the monoclonal antibodies anti-CD26,
      anti-CD30, anti-CD70, anti-CD71, and anti-CD98 using the indirect
      immunoperoxidase method. RESULTS: CD26 is expressed on the glandular epithelium
      in the endometrium and decidua. Endothelial CD26 is expressed less in the decidua
      when compared to the endometrium. CD30 is strongly expressed by decidual cells.
      It is only weakly expressed on endometrial and decidual vessels. Glandular and
      endothelial CD70 expression is mainly seen in the proliferative phase of the
      menstrual cycle. Glandular CD71 expression is less in the decidua when compared
      to the endometrium. Its expression on stromal cells is more in the secretory
      phase of the menstrual cycle and in early pregnancy deciduae. It is expressed on
      endometrial vessels but not on decidual vessels. Glandular CD98 is expressed more
      in the decidua when compared to the endometrium. This antigen exists on
      endometrial lymphocytes. It is strongly expressed on the endothelium in the
      endometrium and decidua. CONCLUSION: It seems that CD26 and CD70 are not involved
      in the functions of endometrial and decidual stromal cells. CD30 and CD71 are
      thought to be involved in decidualization. Absence of activation antigens other
      than CD98 on lymphocytes indicated an antigenic profile for large granular
      lymphocytes that is different from regular lymphocytes.

PMID- 16569932
TI  - Calcium supplementation increases bone mass in GH-deficient prepubertal children
      during GH replacement.
AB  - BACKGROUND/AIMS: Since GH plays an important role in bone mineralization, and
      several studies demonstrated the positive influence of a higher calcium intake on
      bone mass, we studied the effect of calcium supplementation in GHD children
      during GH therapy. METHODS: 28 prepubertal GHD children, 5.0-9.9 years old, were
      assigned to two groups: group A (n = 14; 7 females) treated with GH, and group B
      (n = 14; 7 females) treated with GH + calcium gluconolactate and carbonate (1 g
      calcium/day per os). Auxological parameters, total bone mineral content (TBMC)
      and density (TBMD), leg BMC and BMD, lumbar BMD, fat mass (FM) and lean tissue
      mass (LTM), blood 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH),
      osteocalcin (OC) and urinary N-terminal telopeptide of type I collagen (NTx) were
      determined at the start of therapy and after 1 and 2 years of treatment. RESULTS:
      During the 2 years of the study, TBMC, TBMD, leg BMC and BMD (but not lumbar BMD)
      increased in both groups of patients, however after 2 years of treatment they
      were significantly higher in the calcium-supplemented group B than in group A (p
      < 0.05, for all parameters). At the start of therapy, in both groups of patients
      percentage FM was higher and total and leg LTM lower than in controls (p < 0.05
      for each parameter). Thereafter, FM decreased and LTM increased and after 2 years
      they were both different from baseline (p < 0.05). After 2 years of treatment,
      leg BMC and BMD were more positively correlated with regional leg LTM in patients
      of group B (r = 0.834 and r = 0.827, respectively; p < 0.001) than in patients of
      group A (r = 0.617 and r = 0.637, respectively; p < 0.05). 25-OHD and PTH levels
      were in the normal range in all patients at the start and during treatment. OC
      levels were lower and urinary NTx levels higher in patients than in controls (p <
      0.05 for both parameters), either at the start and after 1 year of treatment.
      After 2 years of treatment, OC levels were significantly higher than at the start
      of the study (p < 0.05) in both groups of patients, but they were higher in group
      B than in group A (p < 0.05); on the contrary, urinary Ntx levels were lower in
      group B than in group A (p < 0.05). CONCLUSION: In GHD children, treated with GH,
      calcium supplementation improved bone mass; it may aid in reaching better peak
      bone mass and in protecting weight-bearing bones, usually completed in childhood
      to maximum levels, from risk of osteoporosis and fractures later in life.

PMID- 16569933
TI  - Ultrasound-guided laser thermal ablation for parathyroid adenomas: analysis of
      three cases with a three-year follow-up.
AB  - BACKGROUND: In patients with primary hyperparathyroidism (pHPT) the therapeutical
      choice is surgery. In patients with high surgical and anesthetic risks,
      ultrasound-guided laser ablation (LTA) of parathyroid adenoma has been reported
      to reduce parathyroid hormone (PTH) hypersecretion without relevant side effects.
      No data are available from patients followed for >6 months. We report our 3-year
      follow-up experience with LTA in 3 patients affected by pHPT due to a parathyroid
      tumor. METHODS: LTA was performed under color-Doppler ultrasound guidance with a
      continuous pulse at 2 W (total treatment duration: 300 s in each session; total
      energy: 1,200 J in two sessions). RESULTS: In the first patient who refused to
      undergo the second LTA session, calcium, PTH levels and parathyroid lesion volume
      showed a slight reduction, returning to baseline values in a month. In the second
      patient, no modification of parathyroid lesion was obtained even if calcium
      levels temporarily normalized. In the third patient, LTA led to normalization of
      calcium and PTH levels and to a 99% reduction of parathyroid volume. CONCLUSION:
      After LTA procedures the long-term disease remission of pHPT is achievable in a
      minority of patients. Data from larger samples are needed to verify the
      usefulness of this procedure.

PMID- 16569934
TI  - Albumin stimulation of eosinophil migration involves PI3-kinases and is
      associated with diminished eosinophil CD49d and CD49f expression.
AB  - BACKGROUND: Albumin is known to induce chemokinesis and facilitate chemotaxis of
      human granulocytes in the Boyden chamber assay, but its mechanisms of action
      remain obscure. We have previously found that IL-2 inhibits albumin-stimulated
      eosinophil migration. The aim of this study was to identify the mechanisms behind
      the effects of albumin and IL-2 on the migration of human eosinophils. METHODS:
      Purified eosinophils were preincubated with inhibitors of signal transduction
      molecules before incubation with or without albumin and IL-2. The migration assay
      was performed in a 48-well microchemotaxis chamber. The effect of albumin and IL
      2 on cell size and on the surface expression of adhesion molecules was studied
      with flow cytometry. RESULTS: Albumin-stimulated migration was inhibited by the
      PI3-kinase inhibitors wortmannin and LY-294002, but not by the PKC inhibitor RO
      31-8220. IL-2 had no effect after preincubation with wortmannin or LY-294002. In
      contrast, the inhibitory effect of IL-2 remained after preincubation with RO-31
      8220. Albumin increased the cell size as measured by forward scatter, and the
      expression of CD49d and CD49f decreased after incubation with albumin. IL-2
      affected neither the expression of adhesion molecules nor the forward scatter.
      CONCLUSIONS: The stimulation of eosinophil migration by albumin is mediated by
      PI3-kinase, and the increase in cell size caused by albumin indicates activation
      of the cells. Decreased expression of CD49d and CD49f by albumin may diminish the
      adhesiveness of the cells, which in turn may facilitate migration. These are
      novel findings that indicate an active role for albumin in eosinophil migration.

PMID- 16569935
TI  - Occupational determinants of cryptogenic polyneuropathy.
AB  - OBJECTIVES: The aim was to investigate different occupational and leisure time
      exposures as determinants for cryptogenic polyneuropathy. METHODS: A case
      referent study was conducted in Sweden including 232 cases of cryptogenic
      polyneuropathy 40-79 years of age at diagnosis who were enrolled from the out
      patient neurology departments of 3 hospitals. From the population register 853
      referents were randomly selected. Information on occupational and leisure time
      exposure was obtained from a postal questionnaire. The response rate was 71% for
      cases and for referents. Crude odds ratios (CORs) and logistic regression odds
      ratios (LORs) were calculated for exposures with 5 or more exposed cases and
      referents taken together. The reference category was defined as individuals
      unexposed to any of the occupational or leisure time risk factors in the
      questionnaire. RESULTS: As expected, male sex and increasing age were significant
      determinants for cryptogenic polyneuropathy. Occupational exposures in men to
      Stoddard solvent, petrol exhausts, herbicides or hand and foot vibrations
      generated significantly increased CORs. LORs >3.50 were found in men for
      occupational exposure to sulphur dioxide, xylene, methyl ethyl ketone, herbicides
      and in women for occupational exposure to lead, nitrous oxide and insecticides.
      Only solvent exposure in leisure time remained significant in the regression
      analysis indicating that not only occupational exposures were of importance.
      Interactions between occupational and leisure time exposure were seen for several
      agents. CONCLUSIONS: Several known determinants for polyneuropathy, from animal
      studies and case reports, were confirmed. New determinants were also indicated,
      i.e. sulphur dioxide, xylene and methyl ethyl ketone.

PMID- 16569936
TI  - Prevalence of epilepsy in a rural district of central Lao PDR.
AB  - PURPOSE: To assess the prevalence of epilepsy in a rural district of Lao PDR and
      to describe the clinical and epidemiological profile of the disease. METHODS:
      Door-to-door screening was performed on the entire population of 8 randomly
      selected villages in the Hinheub district, using an internationally validated and
      standardized questionnaire. Additional passive case detection was performed
      through village key informants. Suspected epilepsy patients identified by the
      questionnaire were revisited and examined by an experienced neurologist on two
      follow-up visits. The confirmation of epilepsy was based only on an in-depth
      clinical examination. Electroencephalograms were performed at the district health
      care center. RESULTS: In the 8 villages, 277 suspected cases of epilepsy were
      identified among 4,310 interviewed subjects; 194 of whom (70%) underwent a
      clinical examination by a neurologist during the first visit while 65 of 83
      remaining suspected cases were seen on the second confirmation visit. Twenty
      seven persons with epilepsy were identified. Six additional patients were
      diagnosed in 219 self-referred subjects. An overall prevalence of 7.7 cases of
      epilepsy per thousand inhabitants was calculated (95% CI 5.3-10.7). Generalized
      epilepsy (21 cases, 63.6%) was commoner than partial epilepsy (9 cases, 27.3%).
      The remaining 3 cases (9.1%) were not-classifiable as either generalized or
      partial. EEG abnormal findings were found in 12 of the 24 patients (50.0%) who
      had an EEG registration. CONCLUSIONS: This is the first study in Lao PDR to
      estimate the prevalence of epilepsy. Compared to Western countries it shows a
      pattern towards a higher prevalence.

PMID- 16569937
TI  - Theophylline and dexamethasone induce peroxisome proliferator-activated receptor
      gamma expression in human eosinophils.
AB  - Eosinophils are major effector cells in allergic diseases including asthma.
      Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear
      receptor that regulates immune reaction. We have previously demonstrated that
      human eosinophils express PPARgamma and that stimulation with a synthetic agonist
      for PPARgamma attenuated the factor-induced eosinophil survival and chemotaxis.
      However, the modulator of the eosinophil PPARgamma expression has not yet been
      studied. In this study, we investigated the effect of theophylline and
      dexamethasone (widely used drugs in the treatment of asthma) on PPARgamma
      expression in eosinophils. Purified human peripheral blood eosinophils were
      cultured, and therapeutic concentrations of theophylline and dexamethasone were
      added. Subsequently, PPARgamma was measured using quantitative real-time RT-PCR
      and flow cytometry. Theophylline and dexamethasone markedly enhanced both mRNA
      and protein levels of PPARgamma. These findings suggest that the increase in
      PPARgamma expression on eosinophils may play a role in the anti-inflammatory
      effects of theophylline and dexamethasone.

PMID- 16569938
TI  - Antagonistic activity of ascorbic acid (vitamin C) on dopaminergic modulation:
      apomorphine-induced stereotypic behavior in mice.
AB  - Among the various neurotransmitter systems implicated in the mechanism of action
      of ascorbic acid (vitamin C), the relationship between the dopaminergic system
      and ascorbic acid is not particularly clear. Ascorbic acid is speculated to have
      an antagonistic effect on dopaminergic modulation. With this background in mind,
      in the present study we have seen the effect of ascorbic acid per se and in
      combination with typical and atypical antipsychotic agents against apomorphine
      induced stereotypic behavior in mice. Male Laka mice weighing 20-25 g were used
      in the present study. Apomorphine-induced stereotypic behavior was used as an
      animal model. Various dopaminergic modulators were used. Ascorbic acid dose
      dependently inhibited stereotypic behavior produced by apomorphine in mice. It
      potentiated the antipsychotic activity of haloperidol (0.1 mg/kg i.p.), a typical
      antipsychotic agent. When administered along with atypical antipsychotics,
      clozapine (1-2 mg/kg i.p.), sulpiride (10-20 mg/kg i.p.) and risperidone (0.0025
      mg/kg i.p.), ascorbic acid also potentiated their activity. Also when given along
      with SCH-23390, a selective D(1) antagonist, an additive effect was observed.
      Ascorbic acid also inhibited the supersensitization response of apomorphine on
      reserpinization (2 mg/kg i.p.). Interestingly, at a lower dose (100 mg/kg i.p.),
      ascorbic acid potentiated the dopaminergic activity of apomorphine (0.5 mg/kg)
      and BHT-920 (0.25 mg/kg i.p.). However, when given concomitantly with SKF-38393,
      it failed to alter the response of SKF-38393. The data substantiate the
      hypothesis that ascorbic acid potentiated the activity of typical as well as
      atypical antipsychotics and that the effect of ascorbic acid on the dopaminergic
      system is markedly dose dependent; a low dose (100 mg/kg i.p.) potentiated the
      dopaminergic action while higher doses (400-1,600 mg/kg i.p.) blocked it.

PMID- 16569941
TI  - The role of information technology in evidence-based practice.

PMID- 16569939
TI  - Curriculum fit for clinical nurse specialists.

PMID- 16569942
TI  - Resources for determining or evaluating sample size in quantitative research
      reports.

PMID- 16569943
TI  - Pharmaceutical advertising and clinical nurse specialist practice.

PMID- 16569944
TI  - Developing your corporate look.

PMID- 16569945
TI  - A collaborative community-based oral care program for school-age children.
AB  - PURPOSE/OBJECTIVES: In Vermont in 2001, less than half of school-age children on
      Medicaid received dental services. Vermont is a designated resettlement area for
      refugees, many of whom have never had dental care. A school-based oral health
      program was designed to meet the needs of this high-risk pediatric population.
      PROGRAM: A plan was developed to offer dental services to this group of children.
      Through the efforts of a multidisciplinary committee the Tooth Tutor Program,
      developed by the Vermont Department of Health, dental care was made available to
      the children. The Tooth Tutor Program provides cost-effective dental hygienist
      care to children in the school setting and includes referral to community
      dentists. OUTCOME: The program was able to provide services to approximately 500
      children in the first 2 years with an increase in preventative services and
      decrease in restorative services from year 1 to year 2. After 3 years, a school
      based dental service opened in 1 of the 3 target schools. CONCLUSION: A school
      based dental service that includes education, screening, and referral can be an
      effective program for improving oral health among impoverished children.
      IMPLICATIONS FOR NURSING PRACTICE: For the community health clinical nurse
      specialist, the client is the community. Clinical nurse specialist practice in
      this community resulted in improved oral health for high-risk school-age
      children. This program can be adapted for other communities.

PMID- 16569948
TI  - Directory of clinical nurse specialist programs in the United States, 2005.
AB  - Interest in clinical nurse specialist (CNS) programs continues to increase as
      market demands for CNSs have risen. Schools of nursing are responding to this
      demand by expanding existing programs and opening new programs. In 2003, the
      National Association of Clinical Nurse Specialists (NACNS) published a Directory
      of Clinical Nurse Specialist Programs. Since that publication, NACNS has
      continued to update this directory as they receive written notification of new
      programs or changes in program offerings. This year, the Education Committee of
      NACNS updated the existing Directory information using data from the 2004
      American Association of Colleges of Nursing and NACNS survey of clinical nurse
      specialist master's level programs. This article provides a current list of CNS
      programs in the United States.

PMID- 16569946
TI  - Strategies to increase research-based practice: interplay with unit culture.
AB  - PURPOSE: A major focus of clinical nurse specialist nursing practice is the
      integration of research findings into practice. The purpose of this study was to
      describe strategies used to facilitate research utilization (RU) by nurses in a
      practice setting. DESIGN: This multiple-case study identified the strategies that
      clinical nurse specialists and master's degree-prepared nurse educators, working
      collaboratively, used to facilitate RU. SETTING/SAMPLE: The setting included 8
      units in 4 sites of a university hospital with all willing nurses participating.
      METHODS: Open-ended focus groups and individual interviews and observational
      sessions were conducted using investigator-designed interview guides.
      Comprehensive qualitative analysis led to identification of categories and themes
      related to RU and the unit culture that supported it. FINDINGS: Findings
      demonstrated that strategies to facilitate RU by staff at the unit level included
      conducting original research, supporting nurses participating in research,
      assessing and meeting staff learning needs, promoting staff attendance at
      conferences, stimulating goal-setting for presentations and publications,
      encouraging and responding to new ideas, questioning practice and stimulating
      inquiry, capitalizing on expertise in research knowledge and skills, and
      generating information and material resources. Characteristics of unit culture
      were linked to varying degrees of success with these strategies. The interplay of
      strategies with unit culture and research-based practice is described.
      CONCLUSION: A wide repertoire of strategies is needed to facilitate RU, and the
      outcome of these strategies is influenced by the unit culture. IMPLICATIONS FOR
      PRACTICE: Consideration of the findings and the scope of the strategies used by
      nurses in the study can help clinical nurse specialist and other nursing leaders
      facilitate the building of practice on research.

PMID- 16569951
TI  - The team approach to dental implants.

PMID- 16569956
TI  - "PASS" principles for predictable bone regeneration.
AB  - Guided bone regeneration is a well-established technique used for augmentation of
      deficient alveolar ridges. Predictable regeneration requires both a high level of
      technical skill and a thorough understanding of underlying principles of wound
      healing. This article describes the 4 major biologic principles (i.e., PASS)
      necessary for predictable bone regeneration: primary wound closure to ensure
      undisturbed and uninterrupted wound healing, angiogenesis to provide necessary
      blood supply and undifferentiated mesenchymal cells, space maintenance/creation
      to facilitate adequate space for bone ingrowth, and stability of wound and
      implant to induce blood clot formation and uneventful healing events. In
      addition, a novel flap design and clinical cases using this principle are
      presented.

PMID- 16569957
TI  - Early osteotomy with delayed implant placement: a step further for immediate
      loading.
AB  - The commonly used implantation technique involves a 2-stage surgical protocol for
      load-free and submerged healing to ensure predictable osseointegration. This
      article presents a new approach that benefits from previous bone and soft tissue
      protocols. It combines new surgical and insertion techniques to perform immediate
      loading with delayed implant placement, avoiding the problems of discomfort,
      inconvenience, and anxiety associated with healing periods. It maintains a
      similar success rate to the present common technique. After osteotomy, bone
      healing passes through 3 stages (i.e., inflammation, fibrous tissue, and
      maturation). In the new approach, implant insertion is performed 2 weeks after
      drilling (i.e., during the fibrous phase). The insertion timing is so selected
      because collagen formation and revascularization represent an acceptable implant
      bed configuration. Flap surgery offers the optimal osteotomy approach, but
      esthetic outcomes are definitely compromised. Accordingly, adopting the punch
      technique alleviates several postoperative problems, such as pain, tenderness,
      and swelling. Moreover, the punch technique avoids the sutures needed to adjust
      the gingiva around the abutment. It provides both cosmetic and functional
      properties.

PMID- 16569958
TI  - Attachment systems for implant retained overdentures: a literature review.
AB  - This article presents a comparison between different attachment systems used to
      retain and support maxillary and mandibular overdentures in completely edentulous
      patients. A literature review based on a MEDLINE search limited to English
      language articles published from 1988 to the present was performed, and a large
      number of attachments available in the dental market were reviewed with regard to
      several factors, including: (1) implant survival rate, (2) marginal bone loss,
      (3) soft tissue complications, (4) retention, (5) stress distribution, (6) space
      requirements, (7) maintenance complications, and (8) patient satisfaction. These
      factors are considered essential for the successful outcome and good long-term
      prognosis of the prostheses. Selection criteria previously published in the
      literature are discussed as well. Product names and manufacturers are mentioned
      only if related to attachment systems, as they are cited in the original
      articles.

PMID- 16569959
TI  - Immediate loading of implant overdentures using modified loading protocol.
AB  - To our knowledge, this study shows the first longitudinal results (range 12-30
      months) of immediate loading of implant-support overdenture with ball attachment
      connection placed in the anterior mandible. Immediately after surgery, the
      overdenture was connected to the implants with 2-ball attachments. The housings
      were filled with Impregum (3M Espe AG; Seefeld, Germany) impression material to
      provide retention as well as reduce forces in the initial phase of loading. Of
      the 28 implants placed, only 1 failed; the 1 failed implant for total implants
      placed represents a success rate of 96.4%. The minimal bone loss (1 mm) in 2
      sites represents a success rate of 92.8%.

PMID- 16569960
TI  - Surgical navigation in oral implantology.
AB  - The ability to generate 3-dimensional volumetric images of the maxillofacial area
      has allowed surgeons to evaluate anatomy before surgery and plan for the
      placement of implants in ideal positions. However, the ability to transfer that
      information to surgical reality has been the most challenging part of implant
      dentistry. With the advent of computer-assisted surgery, the surgeon may now
      navigate through the entire implant procedure with extremely high accuracy. A new
      portable laptop navigated system for oral implantology is discussed as an adjunct
      for complex implant cases.

PMID- 16569961
TI  - Alveolar distraction osteogenesis before placement of dental implants.
AB  - Distraction osteogenesis of the edentulous alveolar ridges may be considered an
      alternative to many other augmentation oriented surgical techniques. It is now
      being widely used for treating severe forms of alveolar ridge atrophy, especially
      before the placement of dental implants. Leibinger Endosseous Alveolar
      Distraction System (LEAD; Stryker Leibinger, Kalamazoo, MI) is an intraosseous
      distraction device used for edentulous ridges. In this study, the healing was
      uneventful in all 5 cases that were treated except 1, in which the vitality of
      the distraction segment could not be maintained. No complications related to the
      prosthodontic restoration were observed.

PMID- 16569962
TI  - Titanium membranes in prevention of alveolar collapse after tooth extraction.
AB  - BACKGROUND AND PURPOSE: The resorption of alveolar bone following tooth
      extraction results in a narrowing and shortening of the residual ridge, which
      leads to esthetic and restorative problems, and reduces the bone volume available
      for implant therapy. The aim of this study was to evaluate the prevention of
      alveolar collapse after tooth extraction, using titanium membrane (Frios
      Boneshield; DENTSPLY Friadent, Mannheim, Germany), associated (or not) with
      autologous bone graft. MATERIALS AND METHODS: A total of 10 nonsmoking healthy
      subjects, ranging from 35 to 60 years old, were selected for this study. Each
      patient had a minimum of 2 uni-radicular periodontally hopeless teeth, which were
      scheduled for extraction. After the procedure, 2 titanium pins were fixed on the
      vestibular bone surfaces that were used as references for the initial measures
      (depth, width, and height) of the socket. Of the sockets,1 was randomly chosen to
      be filled with autologous bone graft (test) removed from superior maxillary
      tuber, and the other one did not receive the graft (control). A titanium membrane
      was adapted and fixed, covering the sockets, which remained for at least 10
      weeks. After a 6-month healing, the final measures were performed. RESULTS: There
      was exposure of the membrane in 5 of the 10 treated subjects. Average bone
      filling (+/-standard deviation) among the 10 subjects was 8.80 +/- 2.93 mm (range
      4-13) in the control group and 8.40 +/- 3.35 mm (range 4-13) in the test group.
      Average bone loss in width in both group was 1.40 +/- 1.97 mm (range -4-1) in the
      control group and 1.40 +/- 0.98 mm (range -4-0) in the test group. There was no
      significant statistical difference between groups considering the evaluated
      standards. CONCLUSION: The use of titanium membrane, alone or in association with
      autogenous bone, favored the prevention of alveolar ridge after tooth extraction.
      This membrane seems to be a possible and safe alternative to other nonresorbable
      membranes when the prevention of alveolar ridge resorption is the objective.

PMID- 16569963
TI  - Analysis of aspartate aminotransferase and alkaline phosphatase in crevicular
      fluid from implants with and without peri-implantitis.
AB  - PURPOSE: The aim of this investigation was to determine the presence of aspartate
      aminotransferase (AST) and alkaline phosphatase (ALP) in crevicular fluid
      collected from implants with and without clinical and radiographic signs of peri
      implantitis. MATERIALS AND METHODS: There were 17 implants with symptoms of peri
      implantitis in 12 subjects, including 4 females and 8 males, compared to 17
      implants in 13 subjects, including 5 females and 8 males, with healthy peri
      implant tissues. Filter paper strips were used to collect peri-implant crevicular
      fluid for 30 seconds in the base of the crevice/pocket. SPSS statistical software
      (SPSS, Inc., Chicago, IL) was used to determine AST and ALP activity. RESULTS:
      The results showed that there was a significant difference in the activity of AST
      and ALP between the 2 study groups (P < 0.0001). AST activity was significantly
      associated with the amount of bleeding on probing (P = 0.02), but no statistical
      correlation was found between ALP activity and increased amount of bleeding on
      probing (P = 0.05). CONCLUSIONS: Within the limits of this study, our results may
      suggest that peri-implant crevicular fluid analysis could be further investigated
      in longitudinal studies as a suitable diagnostic strategy in the evaluation of
      dental implants.

PMID- 16569964
TI  - Collagen fiber orientation near a fractured dental implant after a 5-year loading
      period: case report.
AB  - PURPOSE: Fracture of an implant is one of the possible complications of dental
      implants. It is a quite rare event but of high clinical relevance. Nevertheless,
      it represents an important opportunity for evaluating the peri-implant bone
      tissue response to implant overloading in human beings. The aim of the present
      study was a scanning electron microscopy evaluation of a screw-shaped implant
      retrieved because of fracture and a birefringence analysis of the tissue near the
      fractured implant. MATERIALS AND METHODS: There was 1 fractured screw-shaped
      implant retrieved from a patient with a trephine bur, and it was processed for
      histology. The specimen was analyzed under both scanning electron microscopy and
      circularly polarized light microscopy. RESULTS: The scanning electron microscopy
      fractography analysis showed the typical signs of a fatigue-fracture, with large
      plastic deformations on the implant. The fracture seemed to start from the
      internal coil of the implant. Under circularly polarized light microscopy
      investigation, a bone-implant contact percentage of 81.6% +/- 1.5% (mean +/-
      standard deviation) was found. The amount of the transverse collagen fibers was
      of 68.3%, and the amount of the longitudinal collagen fibers was of 31.7%. The
      difference was statistically significant for z = 2.247 (P = 0.025). CONCLUSION:
      The fracture of the implant was most probably correlated to a fatigue of the
      material mainly associated to a lesion of the internal coil. The high level of
      bone-implant contact percentage was correlated to a predominant transverse
      collagen fiber orientation of the collagen fibers in the peri-implant bone.

PMID- 16569966
TI  - Heat transfer of impression plasters to an implant-bone interface.
AB  - PURPOSE: The purpose of this in vitro study was to measure heat generated at the
      implant-bone interface caused by exothermic setting reaction of 2 impression
      plasters. MATERIALS AND METHODS: The study consisted of 20 titanium-alloy
      abutment impressions connected to a titanium-alloy cylindrical implant embedded
      in an acrylic-resin mandible in a 37 degrees C water bath. There were 2 types of
      impression plaster used, Snow-White (Kerr, Romulus, MI) and Xantano (Kulzer,
      Dormagen, Germany). Temperature changes were recorded via embedded thermocouples
      at the cervix and implant surface apex. Analysis of variance for repeated
      measures was used to compare 2 treatment groups. RESULTS: Temperature increased
      less at the implant apex (1.5 degrees-2.1 degrees C) than at the implant cervix
      (7.4 degrees-10.5 degrees C). Differences between the 2 impression plasters were
      statisticallysignificant only at the implant cervical level (P < 0.05). A lower
      temperature increase was shown with the Snow-White compared with the Xantano.
      Although both plasters generated an exothermic reaction on setting (mean
      temperature change 22 degrees C), the increase in the temperature rate of the
      Snow-White was slower than the Xantano. CONCLUSIONS: Under the conditions of the
      present study, Snow-White impression plaster appears to be safer to use in
      implant prosthodontics compared with the Xantano because of its slower and lower
      exothermic reaction at the implant-bone interface. However, use of the material
      with the rapid setting time would require more care, such as limiting the volume
      of material used (e.g., by using a custom tray).

PMID- 16569965
TI  - Profilometric and standard error of the mean analysis of rough implant surfaces
      treated with different instrumentations.
AB  - PURPOSE: This study evaluated, in vitro, the effects of different
      instrumentations used in the treatment of peri-implantitis on implant surfaces
      coated with hydroxyapatite or titanium plasma spray (TPS). MATERIALS AND METHODS:
      There were 14 cylindrical rough implants used, including 7 hydroxyapatite and 7
      TPS coated. Split in 2 parts for a total of 24 experimental surfaces, implants
      were treated with a stainless-steel curette, plastic curette, ultrasonic scaler
      tip, and air-powder-water spray. There was 1 hydroxyapatite and 1 TPS implant
      used as controls. Profilometry and scanning electron microscopy were used to
      examine instrumented surfaces for variations in surface topography. RESULTS: All
      experimental procedures determined changes on tested rough implant surfaces. Such
      alterations were related to the implant coating material, and the procedure
      consisting in coating removal and/or leveling of surface roughness. CONCLUSION:
      Although a plastic curette and air-powder-water spray induced less implant
      surface alterations, these instrumentations left deposits on the surface that may
      affect, in vivo, the tissue healing process.

PMID- 16569967
TI  - Comparison of bone grafting materials in human extraction sockets: clinical,
      histologic, and histomorphometric evaluations.
AB  - PURPOSE: Although there are a number of bone replacement graft materials that are
      currently available for clinical use, there are few studies that directly compare
      efficacy among graft treatments before implant placement. The purpose of this
      report was to compare 3 bone replacement graft materials (PepGen P-15 228 FLOW
      [DENTSPLY Friadent CeraMed, Lakewood, CO], Puros [Zimmer Dental, Carlsbad, CA],
      and C-Graft 228 [Clinician's Preference, Golden, CO]) for bone formation by
      clinical, histologic, and histomorphometric evaluation. MATERIALS AND METHODS: In
      this prospective, intraoral pilot study, 13 maxillary sockets in 2 patients (both
      smokers) were grafted immediately after tooth extraction with C-Graft 228, Puros,
      or PepGen P-15 228 FLOW (containing additional PepGen P-15 228 particles; FLOW
      PUTTY). After 4 months, bone cores were retrieved and analyzed histologically.
      RESULTS: PepGen P-15 228 FLOW PUTTY produced a significantly (P <0.01) higher
      amount of vital bone than C-Graft 228 or Puros. The amount of vital bone for FLOW
      PUTTY was 12-fold higher than for C-Graft 228 and 4-fold higher than Puros. Of 7
      FLOW PUTTY treated sites, 7 showed >14% vital bone versus 0 of 3 C-Graft 228 and
      0 of 3 Puros treated sites. FLOW PUTTY treated sites showed new vital bone
      between particles of residual graft. C-Graft 228 treated sites showed residual
      particles in a background of connective tissue with very little bone. Puros
      treated sites showed nonvital bone particles in a background of connective
      tissue, with some new vital bone forming around the nonvital bone. CONCLUSION:
      PepGen P-15 228 FLOW PUTTY produced significantly greater vital bone as compared
      to Puros and C-Graft 228 after 4 months. A larger clinical study is required to
      confirm these results.

PMID- 16569968
TI  - Effect of microcapsules containing TAK-778 on bone formation around
      osseointegrated implants: histomorphometric analysis in dogs.
AB  - PURPOSE: The aim of this study was to evaluate the in vivo effect of TAK-778 on
      osseointegration of titanium implants. MATERIALS AND METHODS: Mandibular
      premolars were extracted from 8 dogs. After 3 months, 2 titanium implants were
      bilaterally placed, and each implantation site randomly received 1 of the
      following treatments: sustained-release microcapsules of TAK-778, placebo
      microcapsules, or no treatment. At 8 and 12 weeks after implantation, the hemi
      mandibles containing the implants were removed, and processed for morphologic and
      histomorphometric analysis. Data were submitted to 2-way analysis of variance.
      RESULTS: The histologic sections of the 3 experimental groups at 8 and 12 weeks
      did not show morphologic differences related to applied treatment. The percentage
      of bone-implant contact, mineralized bone matrix between implant threads, and
      mineralized bone matrix within mirror area were not affected either by treatments
      or evaluated periods. CONCLUSIONS: No effect of TAK-778 was observed on
      osseointegration of titanium implants, which most likely occurred because
      microcapsules may not be retained and, therefore, available at the implant sites.
      An alternative is the manufacture of a release system, which can be immobilized
      on implant surface, ensuring the drug permanence in the implant site at least at
      the initial periods of bone formation.

PMID- 16569969
TI  - Implant recommendation as a replacement option after tooth loss for periodontal
      reasons.
AB  - PURPOSE: The aim of this study was to examine the frequency of implant
      recommendation by general dental practitioners to patients who had extractions as
      a result of periodontal disease and factors that influenced their decisions.
      MATERIALS AND METHODS: Dentists in each of 20 general dental practice centers in
      Kuwait were asked to document replacement options given to patients after all
      tooth extractions performed for periodontal reasons within a 30-day period. The
      association of demographic and medical/dental history variables with the decision
      to recommend an implant was statistically tested. RESULTS: A total of 711
      patients with a mean age +/- of 47.34 +/- 0.45 years (range 18-96) had 2202 teeth
      extracted for periodontal reasons during the study period. Only 21 implants for
      12 patients were offered as a replacement option (1.7%). Factors significantly
      associated with a less likelihood of implant recommendation included older age,
      male gender, diabetes mellitus, inadequate compliance with regular periodontal
      maintenance visits, inadequate oral hygiene practices, and anterior tooth types
      (P < 0.05; chi test). CONCLUSION: Dental implants were rarely recommended to
      patients losing their teeth for periodontal reasons by general dentists in
      Kuwait.

PMID- 16569970
TI  - Beyond peak oxygen uptake: new prognostic markers from gas exchange exercise
      tests in chronic heart failure.

PMID- 16569971
TI  - Guiding exercise using the talk test among patients with coronary artery disease.

PMID- 16569973
TI  - Exercise intensity: a matter of measuring or of talking?

PMID- 16569974
TI  - Hemostatic responses to resistance training in patients with coronary artery
      disease.
AB  - PURPOSE: This study was undertaken to evaluate changes in coagulation and
      fibrinolytic responses to an acute bout of resistance training in patients with
      coronary artery disease. METHODS: Fourteen low-to-moderate risk men (mean age,
      57.6 +/- 9 years; body mass index, 26.7 +/- 4.0 kg/m) with known coronary artery
      disease participated in this study. All subjects were recruited from the
      hospital's outpatient cardiac rehabilitation program and none were participating
      in a resistance training exercise program at the time. Using 8 different
      resistance training devices, each subject performed 1 set of 10 repetitions to
      volitional fatigue, resting 1 minute between sets. Blood samples (5 mL) were
      drawn preexercise, immediate postexercise, and 1 hour postexercise in the seated
      position. All values were corrected for plasma volume changes. Alterations in von
      Willebrand Factor antigen, tissue plasminogen activator antigen, and plasminogen
      activator inhibitor-1 activity were analyzed using repeated measures analysis of
      variance. RESULTS: Although von Willebrand Factor antigen remained unchanged from
      preexercise values, tissue plasminogen activator antigen and plasminogen
      activator inhibitor-1 activity increased and decreased, respectively, in the
      immediate postexercise recovery period. Moreover, the latter reduction persisted
      at 1 hour postexercise. CONCLUSION: An acute bout of resistance training improves
      fibrinolytic potential in men with coronary artery disease, without elevating
      thrombotic potential. These data support the safety of resistance training in
      this population when contemporary prescriptive guidelines are used.

PMID- 16569975
TI  - Resistance training: does it alter lytic potential?

PMID- 16569976
TI  - Chronotropic incompetence and its contribution to exercise intolerance in older
      heart failure patients.

PMID- 16569977
TI  - Revisiting the connection between heart rate response during exercise and
      morbidity in patients with heart failure.

PMID- 16569979
TI  - Psychometric evaluation of the heart surgery symptom inventory in patients
      recovering from coronary artery bypass surgery.
AB  - PURPOSE: The purpose of this study was to evaluate the test-retest reliability,
      internal consistency, and concurrent validity of the Heart Surgery Symptom
      Inventory (HSSI) in patients following coronary artery bypass surgery. METHODS:
      This study included 28 patients attending outpatient rehabilitation who had
      undergone coronary artery bypass surgery within the past 6 months. Patients
      completed self-report instruments including a medical history form, HSSI, and
      Medical Outcomes Study Short Form-36. Patients also completed a second HSSI at a
      later time on the same testing day. HSSI scores were summed to create a total
      score and 4 subcategory scores (general, cardiac, trunk, lower extremity).
      Correlations were calculated for scores obtained during 2 trials of the HSSI to
      evaluate test-retest reliability, between individual items, subcategory, and
      total scores to evaluate internal consistency, and between HSSI scores and
      Medical Outcomes Study Short Form-36 scores to evaluate concurrent validity.
      RESULTS: Correlations for the 2 trials of the HSSI total and all subcategories
      were significant (P < .05) and ranged from 0.89 to 0.99. Subcategories to total
      correlations were all significant and ranged from 0.59 to 0.85. Subcategories to
      subcategory correlations were all significant except for lower extremity to
      cardiac and lower extremity to general comparisons. Individual item to total
      correlations ranged from 0.02 to 0.84. Individual item to subcategory
      correlations ranged from 0.01 to 0.85. The correlations between the HSSI total
      and all Medical Outcomes Study Short Form-36 scores were significant.
      CONCLUSIONS: Results indicate that the HSSI has appropriate reliability and
      validity for clinical and research applications. The HSSI can be a useful
      clinical and research tool to evaluate quality of life in patients after coronary
      artery bypass surgery.

PMID- 16569978
TI  - A qualitative approach to developing a patient-derived intervention to increase
      exercise in peripheral arterial disease.
AB  - OBJECTIVE: In designing a patient-physician communication intervention, we
      explored patients' perceptions of the role of exercise in the treatment of
      peripheral arterial disease (PAD). METHODS: We conducted qualitative interviews
      (5 focus groups and 13 one-on-one interviews) involving 35 patients with known
      PAD. We analyzed verbatim transcripts for significant dimensions of patients'
      explanatory models of PAD and exercise, perceptions of patient-physician
      communication, and other factors that would increase their participation in
      exercise (ie, walking). We used Atlas.ti software to facilitate data sorting and
      storage. RESULTS: Based on 30 emerging codes, we identified primary themes that
      constitute patients' perceptions of (1) the causes and outcomes of PAD, (2) the
      importance of patient-physician communication, (3) the impact of PAD on their
      lives, and (4) the factors that would lead to their exercise participation to
      treat PAD. From this information, our conceptual model focuses on an intervention
      plan that includes addressing the known causes of PAD, the patient's behavior
      prior to the diagnosis of PAD, and the factors that shape a patient's overall
      assessment of the role of exercise for PAD. An integral aspect of our model is
      the impact of the physician's perception of PAD coupled with the patient's
      perception in order to shape the intervention-a partnership between the physician
      and the patient-that we posit is likely to lead to behavior change. CONCLUSION:
      Based on qualitative data analysis, we developed a patient-derived model to
      influence exercise participation. This model highlights those factors most likely
      to influence behavior change in patients with PAD. The next step is to enact and
      assess an intervention based on this model, to increase physical activity in
      patients with PAD.

PMID- 16569980
TI  - The acute effects of a rollator in individuals with COPD.
AB  - PURPOSE: To investigate whether the acute benefits of rollator use are consistent
      over time in individuals with moderate to severe chronic obstructive pulmonary
      disease. METHODS: Thirty-one stable subjects with chronic obstructive pulmonary
      disease (13 men, 18 women), aged 68 +/- 8 years, with a forced expiratory volume
      in 1 second of 0.7 +/- 0.2 L (33% +/- 12% predicted) and a baseline 6-minute walk
      (6MW) of 261 +/- 68 m, were recruited from a respiratory clinic after completion
      of a pulmonary rehabilitation program. Two 6MWs were performed at baseline, 4
      weeks, and 8 weeks, one walking unaided and the other walking with the assistance
      of a rollator. The test order was randomly chosen at baseline, and the same test
      order was used at each time point. The primary outcome measures were distance
      walked in 6 minutes (meters), perceived dyspnea using a modified Borg scale, and
      number of rests taken. RESULTS: Subjects achieved higher 6MW distances during
      assisted compared with unassisted walking at baseline (292 +/- 67 vs 263 +/- 67
      m), 4 weeks (296 +/- 62 vs 275 +/- 63m), and 8 weeks (283 +/- 65 vs 259 +/- 68 m)
      (P = .013), with no time effect (P = .5). In addition, use of a rollator resulted
      in a significant improvement in dyspnea (P = .004) at baseline, 4 weeks, and 8
      weeks, with no time effect (P = .7). The use of a rollator also reduced the
      number of rests taken during the 6MW (P < .001), with no time effect (P = .9).
      CONCLUSIONS: Rollator use resulted in improvements in performance in the 6MW,
      which were consistent over time among individuals with moderate to severe chronic
      obstructive pulmonary disease who walk less than 375 m during an unaided 6MW.

PMID- 16569981
TI  - Impact of customized videotape education on quality of life in patients with
      chronic obstructive pulmonary disease.
AB  - PURPOSE: To compare the impact of a library of pulmonary rehabilitation
      videotapes versus an older videotape and usual care on quality of life and
      ability to perform activities of daily living in persons with chronic obstructive
      pulmonary disease. METHODS: Two hundred fourteen patients diagnosed with chronic
      obstructive pulmonary disease, emphysema, or chronic bronchitis were recruited
      and randomized to receive customized videotapes, standard videotapes, or usual
      care. Outcome measures included the Fatigue Impact Scale, Seattle Obstructive
      Lung Disease Questionnaire, and the SF-36(R) Health Survey. RESULTS: Differences
      in coping skills and emotional functioning on the Seattle Obstructive Lung
      Disease Questionnaire were found among the 174 subjects who completed the study.
      The customized videotape group improved by 8.6 and 4.8 points, respectively,
      whereas the score of the other groups decreased by less than 1 point for the
      coping skills, and the scores of the standard video and the control groups
      decreased by 3.0 and 2.1 points, respectively, for emotional functioning (P <
      .05, all comparisons). The scores using the Fatigue Impact Scale also improved
      for the customized videotape group, whereas the scores of the others remained
      unchanged. Videotape users demonstrated better conversion to and retention of
      exercise habits, with over 80% of customized videotape subjects who reported
      exercise habits at baseline continuing the habits as compared with 40% in the
      usual care group. Sedentary subjects at baseline were more likely to begin and
      maintain exercise if randomized to videotapes. CONCLUSIONS: These findings
      demonstrate increased quality of life, lower fatigue, and better compliance with
      a prescribed exercise regimen among subjects using the customized videotapes.
      There was a significant improvement in emotional functioning and coping skills
      among customized videotape subjects.

PMID- 16569985
TI  - Functional reintegration of prefrontal neural networks for enhancing recovery
      after brain injury.
AB  - Functions of the prefrontal cortex (PFC) are fundamental to learning and
      rehabilitation after brain injuries, but the PFC is particularly vulnerable to
      trauma. We propose approaches to cognitive training that are hypothesized to
      specifically enhance PFC function. We present a theoretical framework that
      generates hypotheses regarding the effects of training on the functional
      integration of processes across distributed networks of brain regions. Specific
      outcome measurements that may be used to test these hypotheses in clinical trials
      are proposed. This neural network-level approach may guide cognitive
      rehabilitation and facilitate development of adjunctive biologic treatments to
      enhance the effects of training.

PMID- 16569984
TI  - Using treatment theories to refine the designs of brain injury rehabilitation
      treatment effectiveness studies.
AB  - Many rehabilitation treatments are difficult to define, resulting in a lack of
      clarity about their essential "active ingredients." Treatment theories can narrow
      the scope of possible active ingredients, by clearly specifying how the treatment
      is believed to act. Efficacy studies of theory-defined treatments assess their
      clinical value, but also advance the science underlying the theory. In addition,
      treatment theories shape inclusion and exclusion criteria by suggesting what
      types of patients may benefit, and shape outcome measures by suggesting where the
      treatment impact should be seen. Finally, treatment theories can assist an
      investigator in the selection of an optimal study design.

PMID- 16569986
TI  - Constraint-based therapies as a proposed model for cognitive rehabilitation.
AB  - This article proposes that constraint-induced therapy represents a theoretical
      model of rehabilitation emerging from basic research with implications for
      cognitive remediation attempts. It provides an overview of current work on
      constraint-induced therapies with a focus on the most widely used of these
      techniques, constraint-induced movement therapy (CIMT). An example from recent
      research in the cognitive sciences demonstrates how underlying principles of the
      CIMT could be used to guide rehabilitative efforts for cognitive dysfunction.
      Limitations and obstacles of applying such an approach are discussed.

PMID- 16569987
TI  - Implications of basic science research for brain injury rehabilitation: a focus
      on intact learning mechanisms.
AB  - Within a theoretical framework for rehabilitation that distinguishes between
      automatic and controlled processes, this article reviews basic science research
      and addresses the following issues: What cognitive abilities remain relatively
      intact after severe traumatic brain injury, and how can we incorporate intact
      skills into rehabilitative techniques? The reviewed research indicates that
      individuals with severe traumatic brain injury (a) generally perform similar to
      controls on cognitive tasks (or task components) that require automatic and
      implicit processes as opposed to consciously controlled processes; (b) can learn
      through implicit learning mechanisms; and (c) can acquire and use automatic
      processes in complex, cognitive task performance.

PMID- 16569988
TI  - Self-regulation and goal theories in brain injury rehabilitation.
AB  - Goal planning is a central concept in the clinical practice of rehabilitation.
      Several disciplines within psychology and medicine have elaborated theories
      related to goal attainment and self-regulation, the process of managing one's own
      goal-directed behavior. These theories may be highly relevant to brain injury
      rehabilitation both to help address characteristic deficits in executive function
      and to teach clients how to manage life tasks outside of formal rehabilitation.
      In this article, we describe testable, theoretically motivated interventions at 2
      levels: the goal level focused on attaining or enhancing performance on
      individual tasks and the self-regulation level of metacognitive processes
      involved in planning and managing one's own goal-directed behavior. We also
      discuss issues in experimental methodology that are important to adapting this
      area of research to brain injury rehabilitation, including consideration of
      cognitive status and other individual differences in selecting the participant
      sample, choice of between-subjects versus within-subjects experimental design,
      and selection of appropriate outcome measures.

PMID- 16569989
TI  - Treatment of post-TBI executive dysfunction: application of theory to clinical
      practice.
AB  - The authors propose a theory-based model for the treatment of post-traumatic
      brain injury executive dysfunction that integrates (1) theories of cerebral
      function and organization, (2) cognitive-behavioral theory of problem solving,
      and (3) learning theory. The model delineates appropriate targets of and methods
      for the treatment of executive dysfunction. A practical application of the
      theoretical model is described in the form of a comprehensive day treatment
      program, Executive Plus. A test of the model is also discussed, focused on the
      comparison of Executive Plus and a standard day treatment program along
      parameters dictated by the model.

PMID- 16569990
TI  - Two approaches to behavior disorder after traumatic brain injury.
AB  - A 3-stage model of intervention is used to contrast the philosophy and treatment
      practices of 2 behavioral approaches to behavior disorder following traumatic
      brain injury. The first referred to here as the Operant Neurobehavioral Approach
      developed from neuropsychology and learning theory. The second referred to as the
      Relational Neurobehavioral Approach builds on the nonaversive behavioral
      techniques of the Operant Neurobehavioral Approach. It also incorporates
      principles of motivational interviewing, places more overt emphasis on the
      therapeutic relationship, and targets staff attributions for aggression in staff
      training. The strengths and weaknesses of both approaches are discussed. It is
      suggested that the Relational Neurobehavioral Approach is more likely to engage
      and/or reengage clients with traumatic brain injury who are resistant to behavior
      change. Research implications are discussed including the need to measure the
      fidelity of all intervention variables.

PMID- 16569991
TI  - Practical and theoretical considerations in designing rehabilitation trials: the
      DVBIC cognitive-didactic versus functional-experiential treatment study
      experience.
AB  - This is a descriptive article outlining issues in the development and
      implementation of a multisite randomized rehabilitation trial for brain injury
      treatment. The goal of this article is to present practical and theoretical
      considerations in designing and conducting multicenter rehabilitation trials.
      Practical issues discussed include (a) treatment setting, (b) patient
      accessibility in determining the research question of interest, as well as
      inclusion and exclusion criteria, (c) research protocol development in the
      context of rehabilitation standard of care, and (d) protocol treatments in the
      context of realistic cost-benefits analysis. Rehabilitation theory is discussed
      as playing an important role designing the specifics of the protocol
      interventions. The Defense and Veterans Brain Injury Center Veterans Health
      Administration cognitive-didactic versus functional-experiential study
      methodology is used for illustrative purposes. This study evaluated 2 alternative
      approaches to treatment: one focusing on underlying cognitive processes and the
      second on errorless learning in everyday functional situations. Lessons learned
      over the course of completing the treatment trial are discussed.

PMID- 16569995
TI  - Management of the patient receiving parenteral biologic therapy.
AB  - Biologic therapies are becoming the preferred treatment option for many complex
      medical conditions, especially in the areas of oncology and immunology.
      Cytokines, monoclonal antibodies, and immunomodulators all have their own
      specific roles, clinical applications, mechanisms of action, and side effects. As
      newer biologic agents are approved and used for treatment, the nurse involved in
      the care of the patient receiving parenteral biologic therapy or in the
      administration of parenteral biologic therapies must know and understand the
      technology and mechanisms of action associated with these agents as well as
      guidelines for their safe administration to ensure positive patient outcomes.
      This article discusses biologic therapies, focusing on monoclonal antibodies used
      in oncology and immunology. The indications, use, and administration of
      parenteral biologic therapies, as well as the nursing management of the patients
      receiving the therapies, are presented.

PMID- 16569996
TI  - Examination of factors that lead to complications for new home parenteral
      nutrition patients.
AB  - Home parenteral nutrition carries a risk of infectious, metabolic, and mechanical
      complications that cause significant morbidity and mortality. This study
      investigated the incidence and the causative factors of these complications that
      occur within the first 90 days after discharge from the hospital to home. Data
      were prospectively collected and analyzed for 97 adult patients. A complication
      developed in one third of the patients, and the majority required
      rehospitalization. Infectious complications were the most prevalent, followed by
      mechanical and then metabolic complications. The authors describe their methods
      of collecting data in a quantifiable manner with the ultimate goal of improving
      patient outcomes.

PMID- 16569992
TI  - Cognitive rehabilitation: the role of theoretical rationales and respect for the
      maturational process needed for our evidence.
AB  - The challenge to presenters at the Galveston Brain Injury Conference held in
      April 2005 was to discuss examples of the use of theory to motivate the design of
      treatments for cognitive deficits resulting from traumatic brain injury. This
      article considers the role of theoretical rationales as well as the new optimism
      embracing neurorehabilitation today. However, caution to respect the maturational
      process needed to adequately prepare treatment evidence for clinical application
      is affected.

PMID- 16569997
TI  - Leading change: Retrospective evaluation of a nurse-led initiative in vascular
      access options for autologous stem cell transplant recipients ranging from
      Hickman catheters to peripherally inserted central catheters.
AB  - Central venous access is essential for patients undergoing autologous
      hematopoietic stem cell transplantation (ASCT). Traditionally, tunneled silastic
      catheters have been inserted in these patients. However, changes in resource
      allocation, resulting in reduced surgery and surgeon time and decreasing toxicity
      associated with ASCT, have caused changes in venous access needs and options.
      This led the advanced practice nurse in the transplant program to evaluate other
      central access devices, which resulted in the introduction of peripherally
      inserted central catheters (PICCs) for this patient population. This study
      reports the results of a retrospective analysis comparing efficacy and
      complication profiles between 50 patients with the traditional Hickman catheter
      and 70 patients with PICCs.

PMID- 16569998
TI  - Hyperemesis gravidarum and the role of the infusion nurse.
AB  - Hyperemesis gravidarum is a potentially serious complication of pregnancy that
      can result in severe maternal malnutrition, affects the normal growth and
      development of the fetus, can precipitate preterm birth, and in extreme cases,
      causes fetal death. The article uses a case study to review the disease process
      and outline the benefits of a team approach to the care of the pregnant woman and
      her unborn child. Treatment interventions, from dietary modifications to total
      parenteral nutrition, are reviewed, with a focus on the effects that normal
      pregnancy physiology has on infusion device selection and the total parenteral
      nutrition formula prescribed.

PMID- 16569999
TI  - A descriptive survey of the different management practices for peripheral IV
      catheters among Greek, Jordanian, and Australian teaching hospitals.
AB  - Peripheral IV catheters (PIVCs) are commonly placed in hospital patients.
      However, there is a lack of evidence on which to base this practice. The aim of
      this study was to assess current knowledge and practice for this procedure in 3
      different cultures. The study collected information from a postal questionnaire
      sent to physicians and nurses in teaching hospitals in Greece, Jordan, and
      Australia. The results gathered from the questionnaire depict a number of
      misconceptions with regard to the management of PIVCs in the 3 healthcare
      organizations selected for the study.

PMID- 16570001
TI  - The changing role of natural killer cells in solid organ rejection and tolerance.
AB  - Natural killer (NK) cells have emerged as a particular focus of interest in
      transplantation due to their ability to distinguish allogeneic major
      histocompatibility complex (MHC) antigens and their potent cytolytic effector
      mechanisms. Once relegated to the field of bone marrow transplantation, NK cells
      have recently been shown to participate in the immune response against solid
      organ allo- and xenografts. These new findings suggest that the role of NK cells
      in solid organ rejection and tolerance needs to be reexamined.

PMID- 16570002
TI  - Extending postgrafting cyclosporine decreases the risk of severe graft-versus
      host disease after nonmyeloablative hematopoietic cell transplantation.
AB  - BACKGROUND: It is unknown whether the duration of systemic immunosuppressive
      treatment after allogeneic nonmyeloablative hematopoietic cell transplantation
      (HCT) might influence the incidence, severity, timing, and/or corticosteroid
      responsiveness of graft-versus-host disease (GVHD). METHODS: We retrospectively
      analyzed outcomes among 185 patients with hematologic malignancies who were given
      grafts from HLA-matched related donors following conditioning with 2 Gy total
      body irradiation alone or in combination with fludarabine between December 1998
      and March 2003. Postgrafting immunosuppression consisted of mycophenolate mofetil
      (days 0-27) in combination with 3 different cyclosporine (CSP) regimens: taper
      from (A) days 35 to 56 (n=107), (B) days 56 to 77 (n=35), and (C) days 56 to 180
      (n=43). RESULTS: The overall incidences of grades II-IV and III-IV acute GVHD,
      and extensive chronic GVHD were 52%, 13%, and 56%, respectively. The duration of
      CSP prophylaxis did not significantly influence the overall rate of acute GVHD
      (grade II-IV), extensive chronic GVHD, or non-relapse mortality. However,
      prolonged administration of CSP (group C) was associated with a significantly
      decreased hazard of grades III-IV acute GVHD (HR 0.2, 95% CI [0.04, 0.9]) and
      with an increased likelihood of discontinuing all systemic immunosuppression (HR
      2.4, 95% CI [1.1, 5.2]) when compared to the shortest course of CSP (group A).
      CONCLUSION: Longer CSP duration decreased the risk of severe GVHD and increased
      the likelihood of discontinuing all systemic immunosuppression after
      nonmyeloablative HCT with HLA-matched related grafts.

PMID- 16570003
TI  - Lumbar bone mineral density in renal transplant patients on neoral and
      tacrolimus: a four-year prospective study.
AB  - BACKGROUND: This prospective study was designed to investigate the long-term
      evolution of bone mineral density (BMD) in kidney transplant recipients. METHODS:
      In 86 patients with functioning grafts, 65 on tacrolimus-based immunosuppression
      and 21 on cyclosporine-based immunosuppression, laboratory parameters and BMD
      measurements in lumbar spine (L2-L4) and femoral neck (FN) were performed by DEXA
      in the first month after transplantation (baseline) and yearly thereafter up to
      the fourth year. RESULTS: BMD did not change at 12 months in lumbar spine nor in
      the FN. Detailed analysis identified three patterns of BMD in lumbar spine at 12
      months: BMD remained stable in 27 patients (31.4%), decreased >2% in 31 (36.0%)
      and increased >2% in 28 (32.6%). Patients with no change or gain presented a
      parallel increase of BMD in FN (P<0.001 in both groups). On multivariate
      analysis, the variables associated with no change or lumbar BMD loss were total
      prednisone dose in grams at 12 months (OR 1.402; 95% CI 1.038-1.893; P=0.028),
      calcitriol levels at 12 months (OR 0.936; 95% CI 0.892-0.982; P=0.007) and lumbar
      BMD at baseline (OR 1.006; 95% CI 1.002-1.010; P=0.002). Late treatment with
      calcium supplements and calcitriol did not improve osteopenia. CONCLUSIONS: One
      third of patients had bone loss mainly during the first year of follow-up. Bone
      loss was associated to higher baseline BMD, high steroid dose, and lower
      calcitriol levels at 1 year. Late administration of calcitriol and calcium
      supplements did not improve posttransplant osteopenia. More than 50% of patients
      were osteopenic 4 years after transplantation.

PMID- 16570004
TI  - Safety and efficacy of steroid withdrawal two days after kidney transplantation:
      analysis of results at three years.
AB  - BACKGROUND: Chronic steroid therapy in spite of myriad side effects is widely
      used in kidney transplantation. This prospective controlled study evaluated
      safety and efficacy of steroid withdrawal at 2 days in kidney recipients
      monitored by surveillance biopsy. METHODS: In all, 300 kidney recipients were
      studied; 150 in second-day steroid withdrawal group and 150 in steroid treated
      group (control group). Immunosuppression was basiliximab induction and
      maintenance was a calcineurin inhibitor and mycophenolate mofetil or sirolimus.
      Biopsy-proven acute rejection (BPAR) was treated by methylpredisolone.
      Surveillance biopsies were completed to evaluate subclinical acute rejection
      (SCAR) and chronic allograft nephropathy (CAN). Primary end point was acute
      rejection. Three-year patient and graft survival, new onset diabetes mellitus
      (NODM), serum creatinine and creatinine clearance were evaluated. RESULTS: Acute
      rejection was diagnosed in 14% in control group and 16% in steroid withdrawal
      group. Three-year patient and graft survival was 89% and 79% in control and 91%
      and 78% in steroid withdrawal group. Serum creatinine and creatinine clearance
      was 1.9+/-0.8 and 59+/-11 in control group and 1.8+/-0.9 mg/dl and 61+/-10
      mls/minute in steroid withdrawal group. Incidence of SCAR and progression of CAN
      were comparable in the 2 groups. At 3-years NODM was diagnosed in 21% in control
      group and 4% in steroid withdrawal group (P<0.01). CONCLUSIONS: Two-day steroid
      withdrawal in kidney transplant recipients did not affect BPAR, SCAR, CAN, graft
      function and patient and graft survival compared to control group up to 3 years.
      NODM was significantly less in steroid withdrawal group. Two-day steroid
      withdrawal is safe and beneficial in kidney transplant recipients.

PMID- 16570005
TI  - Surgical aspects of third and subsequent renal transplants performed by the
      extraperitoneal access.
AB  - BACKGROUND: We reviewed our experience with third, fourth, and fifth renal
      transplants performed by the extraperitoneal access. METHODS: The charts of 21
      third and subsequent transplants performed extraperitoneally were reviewed.
      Surgical aspects, the occurrence of rejection episodes, delayed graft function
      (DGF), graft and patient survival were evaluated and compared with 1560 first
      transplants in adults with nonmanipulated fossa performed in the same period.
      RESULTS: Transfusion was necessary in 52% of the retransplants and in 5.7% of the
      first transplants (P<0.0001). Mean operative time was 327 min for retransplants
      and 212 min for first transplants (P<0.0001). Surgical complications occurred in
      4 patients (19%): two arterial thrombosis and two ureteral obstructions. DGF
      occurred in 11 patients (52%) among retransplants and in 453 (29%) among first
      transplants (P=0.028). Acute rejection occurred in 7 (33.3%) retransplants and in
      530 first transplant patients (33.9%). The mean serum creatinine among
      retransplant patients 30 days and one year after transplantation was 2.5 mg/dl
      and 1.8 mg/dl. One-year graft survival was 57.1% (75% for live and 46% for
      cadaver donors) for retransplants and 86% for first transplant patients
      (P<0.0001). CONCLUSION: Third and subsequent transplants performed
      extraperitoneally are more time-consuming and require more transfusions in the
      perioperative period. A higher but acceptable incidence of arterial thrombosis
      and urinary obstruction were observed. One-year graft survival was better with
      live donor grafts, but was still lower when compared with first transplants using
      the same surgical technique.

PMID- 16570006
TI  - A randomized long-term trial of tacrolimus/sirolimus versus
      tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation:
      three-year analysis.
AB  - BACKGROUND: We report three-year (interim) effects of combining sirolimus (Siro)
      vs. mycophenolate mofetil (MMF) as adjunctive therapy with calcineurin inhibitors
      (CI) in renal transplantation in the three different CI-based regimens. METHODS:
      Between May 2000 and December 2001, 150 recipients of deceased donor (DD) and
      living donor (LD) kidney transplants were randomized into three groups
      (n=50/group): Group A (Tacro/Siro), Group B (Tacro/MMF) and Group C (CsA/Siro).
      This report details drug dosing and monitoring, protocol discontinuance, biopsy
      proven rejection, graft failure, other adverse events, and death at 36 months
      postoperatively. RESULTS: Actual patient and graft survival respectively in Group
      A was 90% and 82%, in Group B was 92% and 88%, and in Group C was 96% and 88%
      (not significant). Biopsy-confirmed acute rejection incidents showed a trend in
      favor of Group B (10%) vs. Group A (26%) and Group C (20%) combined (P=0.07). The
      geometric mean */SE serum creatinine concentration and arithmetic mean +/- SE
      Cockroft-Gault creatinine clearance calculations, respectively, were 1.39*/1.1
      and 72.8+/-4.3 for Group A, 1.36*/1.1 and 72.1+/-4.1 for Group B, and 1.60*/1.1
      and 61.8+/-3.8 for Group C, a statistically favorable difference for Group B over
      Group C (P=0.04). There was also less de novo development of posttransplant
      diabetes mellitus and lipid disorders in Group B vs. A and C (P<0.04).
      CONCLUSIONS: This three-year (interim) analysis has indicated a trend towards
      better graft function, fewer endocrine disorders, and fewer acute rejection
      episodes comparing adjunctive MMF and Tacro vs. Siro and Tacro or Siro and CsA,
      in the dosages used.

PMID- 16570007
TI  - Successful organ transplantation from donors with Acinetobacter baumannii septic
      shock.
AB  - Donor bacteremia with severe sepsis, especially due to gram-negative organisms,
      has been considered a contraindication to transplantation. Over a 6-month period
      we prospectively collected standardized data on all brain-dead, heart-beating
      organ donors with gram negative bacteremia and septic shock and the recipients of
      their organs in hospitals throughout Israel. Donors were treated with appropriate
      antibiotics for at least 48 hr prior to organ retrieval while recipients received
      7 days of culture-specific antibiotics following transplantation. In total, 12
      organs were transplanted (5 kidneys, 2 livers, 3 lungs and 2 hearts) from 3
      donors with Acinetobacter baumannii bacteremia and septic shock. All patients
      were alive with good graft function 60 days following transplantation, apart from
      one of the heart recipients who died of primary nonfunction on the second
      postoperative day. Two recipients developed postoperative infections, none with
      Acinetobacter sp. (one Pseudomonas sp. urinary tract infection, one Klebsiella
      sp. central venous catheter sepsis).

PMID- 16570008
TI  - A randomized trial of ganciclovir versus ganciclovir plus immune globulin for
      prophylaxis against Epstein-Barr virus related posttransplant lymphoproliferative
      disorder.
AB  - BACKGROUND: Transplant recipients who are Epstein-Barr virus (EBV)-seronegative
      and receive organs from seropositive donors (EBV D+/R-) are at increased risk for
      posttransplant lymphoproliferative disorder (PTLD) and may benefit from antiviral
      prophylaxis. We performed a multi-center trial assessing two different antiviral
      regimens and their effect on EBV replication. METHODS: EBV D+/R- solid organ
      transplant recipients were randomized to receive either ganciclovir and placebo
      or ganciclovir and immunoglobulin (IG) for 3 months. Following this, patients
      were unblinded and IG patients received additional IG therapy until 6 months. EBV
      viral loads were done at least monthly. RESULTS.: Thirty-four patients (25
      pediatric, 9 adult) completed the protocol (16 placebo; 18 IG). The incidence of
      a detectable viral load within the first year posttransplant was 13/16 (81.3%) in
      the ganciclovir arm vs. 13/18 (72.2%) in the ganciclovir and IG arm (P=0.8). Time
      to first detectable viral load, and time to high-level viral load were not
      significantly different. By repeated measures ANOVA analysis, and by estimation
      of viral load AUC, no significant effect of randomization group was observed on
      EBV viral loads. PTLD developed in 3 (8.8%) patients (all in IG arm; P=0.23).
      CONCLUSIONS: No significant difference in EBV viral load suppression was observed
      when ganciclovir was compared with ganciclovir and IG in high-risk EBV D+/R-
      patients.

PMID- 16570009
TI  - Successful bilateral lung transplant outcomes in recipients 61 years of age and
      older.
AB  - BACKGROUND: Controversy exists regarding the optimal use of bilateral lung
      transplant (BLT) in older recipients in diseases where either single or bilateral
      transplant is appropriate. International Society for Heart and Lung Transplant
      (ISHLT) guidelines suggest an upper age limit of 60 for BLT, despite limited data
      regarding outcomes with BLT in patients over 60. We hypothesize that BLT offers
      comparable, if not superior, clinical outcomes to SLT in all patients independent
      of recipient age. METHODS: In order to test our hypothesis, we conducted a case
      control study to compare the effect of transplant operation on survival and the
      onset of bronchiolitis obliterans syndrome (BOS) in consecutive lung transplant
      recipients 61 years of age or older using Kaplan- Meier analysis and Cox
      proportional hazard models. RESULTS: We identified 107 consecutive lung
      transplant recipients 61 or older at the time of transplant. Patients received
      SLT (n=46) or BLT (n=61) based on donor organ availability. Comparable survival
      was achieved with BLT in older patients vs. SLT P=0.19). One-, two-, and five
      year survival estimates in BLT were 82%, 75% and 68%, respectively, vs. in SLT
      78%, 70% and 44%, respectively. A comparable onset of BOS was also observed in
      the patients who received BLT vs. SLT (P=0.23). CONCLUSION: Successful short- and
      medium-term outcomes are achieved with BLT in older recipients and are comparable
      to those achieved with SLT. Our results suggest that age over 60 should not
      exclude patients from consideration of BLT.

PMID- 16570010
TI  - Fast appearance of donor dendritic cells in human skin: dynamics of skin and
      blood dendritic cells after allogeneic hematopoietic cell transplantation.
AB  - BACKGROUND: Both number and origin (donor vs. host) of dendritic cells (DC) are
      associated with acute graft-versus-host disease (aGvHD), relapse and graft
      failure after human allogeneic hematopoietic cell transplantation (aHCT).
      METHODS: We prospectively and simultaneously investigated skin and blood DC
      subtypes, their donor/recipient origin, and the correlation of DC reconstitution
      kinetics with treatment, clinical outcome, and incidence of aGvHD in patients
      undergoing aHCT. RESULTS: A significant reduction of skin and a marked decrease
      of blood DC were observed in patients compared to healthy volunteers. A dominant
      donor chimerism of migratory Langerhans cells (LC) and dermal-dendritic-cells
      (DDC) was detected even early after transplantation, and developed independently
      from chemotherapy regimen, graft manipulation or time point after
      transplantation. Before start of the therapy patients showed significantly
      decreased numbers of peripheral blood CD123+ preDC2, whereas CD11c+ preDC1
      numbers appeared to be diminished, but were statistically indistinguishable from
      controls. Host derived pB preDC were virtually absent following aHCT. After a
      further reduction in cell number around day 56 both preDC subtypes reconstituted
      and stabilized to pretransplant numbers by day 112. Occurrence of aGvHD and its
      treatment diminished numbers of both preDC subtypes. Furthermore conditioning
      therapy with Alemtuzumab apparently affected reconstitution of both preDC subsets
      negatively. CONCLUSION: Given that induction of GvHD in humans is as host DC
      dependent as in mouse models, investigation of DC chimerism and number at
      different sites and especially in GvHD target organs might provide important
      insights into the pathogenesis of the main obstacle of aHCT.

PMID- 16570011
TI  - Kidney transplantation with concomitant unilateral nephrectomy: a matched-pair
      analysis on complications and outcome.
AB  - BACKGROUND: We sought to determine the impact of kidney transplantation with
      simultaneous unilateral nephrectomy on perioperative morbidity and patient and
      graft survival. METHODS: From January 1990 to May 2004, 75 kidney
      transplantations with simultaneous unilateral nephrectomy (group NE+) were
      performed at the University of Freiburg. Of these, 49 had polycystic kidney
      disease. Patients of group NE+ were matched with 75 kidney transplants without
      nephrectomy (group NE-). Immunosuppressive maintenance therapy in both groups was
      based on cyclosporine A, mycophenolate mofetil or azathioprine, and prednisone.
      Mean follow up was 4.1 yrs (range 0.3-11.7 yrs). RESULTS: Patient survival rate
      at 1 and 5 yrs was 95% and 84% versus 95% and 93% in group NE+ and NE-, resp.
      (P=0.56). Accordingly, kidney function rate was 85% and 74% in group NE+ versus
      89% and 79% in group NE- (P=0.89). Perioperative (90 days) mortality rate in
      group NE+ was 1.3% and 2.7% in group NE- (P=0.56). Perioperative surgical
      complications were similar in both groups. CONCLUSIONS: Kidney transplantation
      with concomitant unilateral nephrectomy has no negative impact on patient or
      graft survival and is associated with a reasonable morbidity rate.

PMID- 16570012
TI  - Donor nephrectomy: mini-incision muscle-splitting open approach versus
      laparoscopy.
AB  - BACKGROUND: The introduction of laparoscopic donor nephrectomy (LDN) has
      encouraged the development of less invasive open techniques. Aim of the present
      study was to compare short-term outcomes between contemporary cohorts of donors
      who underwent either mini-incision open or laparoscopic kidney donation. METHODS:
      From May 2001 to September 2004 data of all living kidney donations and
      transplantations were prospectively collected. Fifty-one donors underwent mini
      incision, muscle-splitting open donor nephrectomy (MIDN) and 49 donors underwent
      LDN. RESULTS: Baseline characteristics of donors and recipients in the study
      groups were comparable except for donors' gender. Median incision length in MIDN
      was 10.5 cm. In two patients LDN was converted to open. MIDN resulted in
      significantly shorter warm ischemia and operation time (2.5 vs. 6.5 min and 157
      vs. 240 min respectively). During MIDN, donors had more blood loss (200 vs. 120
      ml, P=0.02). Disposables used for MIDN were cheaper (328 vs. 1784 Euros). In the
      LDN group 4 (8%) major intraoperative and 2 (4%) major postoperative
      complications occurred versus no major complications in the MIDN group. Morphine
      requirement, pain and nausea perception, and time to dietary intake did not
      significantly differ between the groups. Following MIDN, donors were discharged
      later (4 vs. 3 days, P=0.02). Transplantation of kidneys procured by either
      approach led to a similar decline in serum creatinine throughout the first year.
      One-year graft survival was 100% following MIDN and 86% following LDN (P=0.005).
      CONCLUSION: MIDN and LDN both lead to satisfactory results. Both techniques can
      be used to expand living donor programs.

PMID- 16570013
TI  - Myeloma, Hodgkin disease, and lymphoid leukemia after renal transplantation:
      characteristics, risk factors and prognosis.
AB  - BACKGROUND: Hodgkin disease and myeloma were recently included in the
      classification of posttransplant lymphoproliferative disorder (PTLD). However,
      because their incidence is low, not much is known about their particular
      features. METHODS: The incidence, characteristics, risk, and prognostic factors
      of myeloma, Hodgkin disease, and lymphoid leukemia using the United States Renal
      Data System from 1991 to 2000 among 66,159 Medicare patients were analyzed.
      RESULTS: In all, 1,169 recipients developed a lymphoid disease: 823 (1.2%) non
      Hodgkin's lymphomas (NHL), 160 (0.24%) myelomas, 60 (0.1%) Hodgkin lymphomas, and
      126 (0.2%) lymphoid leukemias. Older age was associated with an increased risk of
      myeloma and leukemia. The incidence of hepatitis C virus infection was higher in
      recipients with myeloma (6.9 vs. 3.9%, P=0.05). Induction therapy was associated
      with a greater risk of myeloma and leukemia, but not Hodgkin disease.
      Azathioprine was associated with a lower risk of myeloma, and tacrolimus with a
      lower risk of Hodgkin disease. According to the type of malignancy, ten-year
      survival rates were significantly different: 42, 26, 55 and 39% respectively for
      NHL, myeloma, Hodgkin disease, and leukemia. CONCLUSION: These results support
      specific features and risk factors related to the occurrence of each type of
      lymphoid-proliferation and suggest for the first time a possible association
      between hepatitis C virus and myeloma in kidney transplant recipients.

PMID- 16570014
TI  - How effective is penetrating corneal transplantation? Factors influencing long
      term outcome in multivariate analysis.
AB  - BACKGROUND: In a large patient cohort, we investigated long-term corneal graft
      outcome, risk factors for graft failure, and whether corneal graft survival had
      improved over time. METHODS: Records of 10,952 full-thickness corneal grafts with
      associated archival follow-up were examined within a prospectively-maintained,
      national database of 13,831 records, with follow-up extending for up to 18 years.
      Kaplan-Meier survival analysis was used to indicate variables of interest for Cox
      proportional hazards regression analysis. A model clustered by individual patient
      to control for inter-eye or inter-graft dependence was constructed to identify
      variables best predicting penetrating corneal graft failure. RESULTS: Probability
      of corneal graft survival was 0.86 at 1 year, 0.73 at 5 years, 0.62 at 10 years,
      and 0.55 at 15 years. Graft survival did not improve over a 15-year timeframe.
      Variables predicting graft failure in multivariate analysis included transplant
      centre, donor age, preoperative diagnosis, number of previous ipsilateral grafts,
      lens status, history of corneal neovascularisation, ocular inflammation or raised
      intraocular pressure in the grafted eye, requirement for anterior vitrectomy,
      graft size, early suture removal, postoperative events including graft
      neovascularisation, rise in intraocular pressure, and rejection episodes, type of
      treatment for raised intraocular pressure, and arrangements for recipient follow
      up. A further 11 variables showing a significant influence on graft survival in
      univariate analysis were not included in the final Cox model. CONCLUSION: The
      long-term results of corneal transplantation are no better than for other forms
      of transplantation and have shown no measurable improvement over the past 15
      years.

PMID- 16570015
TI  - Angiogenic gene cell therapy using suicide gene system regulates the effect of
      angiogenesis in infarcted rat heart.
AB  - BACKGROUND: Although angiogenic gene therapy has been reported to be effective in
      restoring ischemic heart function, there are several obstacles to its clinical
      application, such as unreliable efficiency of transfection and uncontrollable
      expression. We developed human HGF (hHGF)-producing cells that regulated hHGF
      production using the thymidine kinase gene of Herpes Simplex Virus (TK) and the
      Ganciclovir (GCV) system. We tested whether these cells induced and regulated
      angiogenic effects in infarcted myocardium. METHODS: NIH3T3 cells were stably
      transfected with an hHGF cDNA expression plasmid (NIH/HGF). Next, the NIH/HGF
      cells were stably transfected with TK (NIH/HGF/TK). The left anterior descending
      artery was ligated in the heart of severe combined immunodeficiency rats, and
      four materials were transplanted: 1) NIH/HGF (n=10), 2) NIH/HGF/TK, with orally
      administered GCV (n=10), 3) NIH3T3 (n=10), and 4) culture medium (n=10). RESULTS:
      In vitro, the proliferation of NIH/HGF/TK cells was suppressed by GCV. In vivo,
      significant increases in cardiac performance and angiogenesis were observed in
      the NIH/HGF and NIH/HGF/TK groups 4 weeks after transplantation. Although
      tumorous lesions were detected in the NIH/HGF group, their growth was completely
      controlled in the NIH/HGF/TK group. CONCLUSIONS: Angiogenic gene cell therapy
      using the TK-GCV suicide gene system induces and regulates angiogenesis under the
      control of cell growth, suggesting it as a promising system for therapeutic
      angiogenesis.

PMID- 16570016
TI  - Prevention of chronic renal allograft rejection by SERP-1 protein.
AB  - BACKGROUND: In previous studies we have demonstrated that Serp-1, a myxoma virus
      encoded serine protease inhibitor, dramatically inhibits neointimal hyperplasia
      in vascular injury and aortic transplant models. Here we examined the effect of
      peritransplant Serp-1 administration on chronic renal allograft rejection.
      METHODS: Rat renal transplants were performed with sequential recipient sacrifice
      on postoperative days 2, 10 and 140 to examine both the acute and chronic effects
      of Serp-1 in recipient rats. RESULTS: Serp-1 administration reduced early
      posttransplant injury (POD 2) with less acute tubular and vascular necrosis. This
      translated into a reduction of the characteristic late stage changes of chronic
      rejection (POD 140), with significantly decreased glomerulosclerosis and
      neointimal hyperplasia. Effects of Serp-1 treatment were already evident as early
      as POD 2 with markedly decreased levels of TGF-beta mRNA witnessed at both the
      early and late time points (POD 2, 10 and 140). CONCLUSION: We have demonstrated
      that peritransplant Serp-1 viral protein decreased early injury and allowed
      reduced chronic rejection in a rat renal model. Recipients treated with Serp-1
      are associated with a decrease in TGF-beta mRNA levels in the allografts
      suggesting that the serine protease inhibitor may inhibit TGF-beta transcription
      and its profibrotic effects.

PMID- 16570017
TI  - Bone disease in long-term renal transplant recipients with severe osteopenia: a
      cross-sectional study.
AB  - BACKGROUND: Fracture is a disabling clinical outcome after transplantation, but
      there is little histopathological information on long-term renal recipients with
      severe osteopenia. METHODS: Twenty kidney recipients (8.3+/-1.9 years after
      transplantation), 13 males and 7 females (five postmenopausal) with nearly normal
      renal function, affected by severe osteopenia (T-score: males= -4.9+/-0.28;
      females= -5.08+/-0.47) underwent bone biopsy and morphometric X-ray
      absorptiometry to evaluate vertebral fractures. RESULTS: Histopathological
      diagnosis was osteoporosis-osteopenia in seven patients, osteitis fibrosa in six,
      prevalent osteomalacic lesion in six, and "normal" bone in one patient.
      Significant increases in osteoid volume (OV/BV), osteoid surface, osteoblastic
      surface (ObS/BS) and osteoid thickness were observed. OV/BV and Obs/BS ratios
      were inversely correlated to cumulative doses of MPRED (r2=0.85 P<.0001 for both
      ratios), whereas age, sex, time after transplantation, iPTH levels, and
      cumulative cyclosporine A dose were not related to osteoblastic indices.
      Osteoclast surface was slightly increased. Widened mineralization lag times were
      observed, with normalcy of the bone formation rate. Half of the patients showed
      fractured vertebrae. No differences in T scores were found when patients were
      subdivided into groups "with" or "without" vertebral fractures. A higher
      prevalence of fractures was observed in patients with osteoporosis-osteopenia
      compared to other osteopathies (P<0.02). No relationships between bone volume
      versus T-scores were observed. CONCLUSIONS: In long-term renal transplant
      recipients, severe osteopenia does not predict osteoporosis alone. The main
      abnormality we found was an increase in osteoblastic activity with a slight
      mineralization defect. The heterogeneous bone illness we observed would suggest
      performing bone biopsy in these patients.

PMID- 16570018
TI  - In vivo suppression of major histocompatibility complex class II expression on
      porcine vascular endothelial cells by an HMG-CoA reductase inhibitor.
AB  - BACKGROUND: Vascular endothelial cells of man and pig, but not rodents, strongly
      express major histocompatibility complex (MHC) class II antigens in vivo,
      probably via the inducible promoter IV of the class II transactivator. There is
      abundant in vitro evidence that MHC class II positive vascular endothelial cells
      can activate T cells. Peripheral antigen presentation by endothelial cells is
      potentially important for organ-specific immunity, for allograft rejection, and
      possibly for immune responsiveness in general. Given the reported effects of
      statins on promoter IV of the class II transactivator, we evaluated in vivo
      expression of MHC class II antigens in pigs treated with atorvastatin calcium.
      METHODS: Pigs were given 3 mg/kg/day of atorvastatin orally daily for 16 days,
      and then killed 24 hr after the last dose. Heart, kidney, and liver were removed
      for immunohistological and quantitative absorption analysis. RESULTS: Double
      labeling studies using immunofluorescence on frozen section for Factor VIII and
      MHC class II showed a marked suppression of MHC class II on vascular endothelial
      cells in all 4 treated pigs, in comparison with untreated pigs. This was
      confirmed using immunoperoxidase techniques on frozen sections. Quantitative
      absorption analysis showed up to 25-fold reduction in MHC class II expression.
      CONCLUSIONS: Statins substantially suppress endothelial cell MHC class II
      expression in vivo. This is likely to inhibit organ-specific immune responses,
      and possibly also general immune responsiveness. In a transplantation setting, in
      addition to other regulatory effects on the recipients immune system, statins
      might reduce the long-term capacity of the donor organ to activate rejection
      mechanisms.

PMID- 16570019
TI  - Suppression of (5R)-5-hydroxytriptolide (LLDT-8) on allograft rejection in full
      MHC-mismatched mouse cardiac transplantation.
AB  - BACKGROUND: (5R)-5-hydroxytriptolide (LLDT-8) is a new compound derived from
      triptolide, which is the major immunosuppressive fraction of Tripterygium
      wilfordii Hook. F (TWHF). Studies in vitro and in vivo have demonstrated that
      LLDT-8 had potent immunosuppressive activities. Here we tested LLDT-8 in major
      histocompatibility complex (MHC)-mismatched cardiac transplantation and
      investigated the mechanisms underlying the prevention of transplant rejection.
      METHODS: LLDT-8 was administered orally to recipients in Balb/c to C57BL/6 murine
      cardiac transplantation model. Allograft survival after transplantation was
      recorded in recipients. The T cell immunity and cytokine production were
      observed. Histological analysis was performed. The chemokine and its receptor
      were analyzed by reverse transcriptase-polymerase chain reaction on cardiac graft
      RNA. RESULTS: LLDT-8 administered orally significantly induced the survival
      prolongation of allogeneic cardiac graft. Histological results showed that LLDT-8
      well preserved myocardium and significantly reduced infiltration of the graft
      with inflammatory cells. LLDT-8 decreased IL-2 production in recipient
      splenocytes stimulated by concanavalin A (ConA) ex vivo. LLDT-8 significantly
      inhibited the immunoreactivity of recipient to specific donor alloantigens, but
      preserved immunity to third-party alloantigens and mitogen. However, the flow
      cytometry analysis of the proportion of CD4+, CD8+ T cell subgroup in recipient
      spleens showed LLDT-8 had a normalizing effect on the splenic lymphocytes
      population. LLDT-8 decreased CC chemokine receptor 5 (CCR5) and their ligands
      macrophage inflammatory protein 1 alpha (MIP-1alpha) and beta (MIP-1beta) mRNA
      expressions in allografts. CONCLUSION: The results outline the great potential of
      LLDT-8 as a therapeutic tool in transplant rejection.

PMID- 16570020
TI  - Impact of TGFbeta1 gene polymorphisms on acute and chronic rejection in pediatric
      heart transplant allografts.
AB  - BACKGROUND: The aim of this study was to assess the influence of IL-10 and
      TGFbeta1 gene polymorphisms on the development of acute rejection and coronary
      disease in pediatric heart transplant recipients. METHODS: Patients were
      classified as either Rejectors or Nonrejectors. Coronary artery disease (CAD) was
      diagnosed by angiography or on macroscopic examination. Genotyping PCR-SSP were
      performed for IL-10 and TGFbeta1 (codon 10 and 25) in 111 patients. Thirty-nine
      were Rejectors and 31 developed CAD. RESULTS: The proportion of IL-10 low
      producers was higher in Rejectors than in Nonrejectors (respectively 46% versus
      22%, P=0.009). IL-10 gene polymorphism was not associated with CAD. TGFbeta1
      codon10-25 high-producers were 92.3% in Rejectors and 75% in Nonrejectors
      (P=0.026), 93.5% in patients with CAD and 76.2% in patients free from CAD
      (P=0.037). TGFbeta1-codon25 high-production separately analyzed correlated with
      CAD (31/31 high-producers in CAD=100% versus 69/80 in noCAD patients=86.2%,
      P=0.03). TGFbeta1-codon10 gene polymorphisms were not associated with CAD.
      CONCLUSION: IL-10 low-producers have an increased risk of acute rejection. High
      expressors of TGFbeta1-codon10-25 have an increased risk of acute rejection and
      CAD, while TGFbeta1-codon25 high-production is associated with coronary disease.
      Genetic polymorphism may reveal patients at high-risk in whom therapies and
      monitoring should be adjusted.

PMID- 16570021
TI  - Characterization of anti-Gal antibody-producing cells of baboons and humans.
AB  - BACKGROUND: Anti-Gal antibodies cause hyperacute and delayed xenograft rejection
      in pig-to-primate transplantation. The cell populations producing anti-Gal and
      other natural antibodies in primates are unknown. METHODS: Cells from different
      lymphoid compartments of naive or sensitized baboons were examined for anti-Gal
      and total Ig production by ELISPOT. B and plasma cells from humans and baboons
      were purified by FACS sorting and characterized for anti-Gal and total Ig
      production and cytology. RESULTS: In naive baboons, the spleen was the major
      source of anti-Gal IgM-secreting cells. Two months after sensitization with
      porcine tissues, high frequencies of anti-Gal IgM- and IgG-secreting cells were
      detected in the spleen, lymph nodes, and bone marrow. Six months after antigen
      exposure, anti-Gal IgM- and IgG-secreting cells were preferentially localized in
      the bone marrow. Cells from human spleen, bone marrow, and blood were also
      analyzed and anti-Gal IgM-secreting cells were detected mainly in the spleen.
      Sorting of baboon and human cells showed that anti-Gal IgM-secreting cells were
      mainly splenic B cells (CD20+, CD138-, and Ig+). Although low in percentage,
      sorted CD20-CD138+ plasma cells in spleen and bone marrow secreted large
      quantities of anti-Gal IgM. Most anti-Gal IgG-secreting cells were plasma cells
      (CD138+) at both early (Ig+) and late (Ig-) stages of differentiation.
      CONCLUSIONS: Similar to Gal knockout mice, natural anti-Gal IgM antibodies in
      primates are produced mainly by splenic B cells. After antigen exposure, anti-Gal
      IgM and IgG were secreted by both B and plasma cells. These results suggest
      strategies to remove xenoreactive antibody-secreting cells prior to
      transplantation.

PMID- 16570022
TI  - Comparison of sequential protocol using basiliximab versus antithymocyte globulin
      with high-dose mycophenolate mofetil in recipients of a kidney graft from an
      expanded-criteria donor.
AB  - This retrospective pilot study investigated use of high-dose mycophenolate
      mofetil with biological induction and sequential introduction of low-dose
      cyclosporine in recipients of expanded criteria donor (ECD) kidneys. Fifty-four
      patients received mycophenolate mofetil 3 g/day for 45 days, cyclosporine 4
      mg/kg/day, prednisolone, and rabbit antithymocyte globulin (rATG, n=14) or
      basiliximab (n=40). Acute rejection incidence was 11.3% (7.1% with rATG, 12.6%
      with basiliximab). Delayed graft function was observed in 31 patients (54%). At
      one year, measured glomerular filtration rate was 54+/-4 ml/min, with no
      significant differences between induction therapies. Thirty patients (55%)
      required > or =1 MMF dose reduction within month 1 due to adverse events
      (gastrointestinal symptoms, 67%; leucopenia 33%). Leucopenia was more frequent
      with rATG, while gastrointestinal symptoms were more frequent with basiliximab.
      Cytomegalovirus replication occurred in three patients (23%) with rATG and 3 (8%)
      with basiliximab. In conclusion, high-dose MMF, corticosteroids, delayed low-dose
      cyclosporine and induction therapy offers an excellent risk-to-benefit ratio in
      patients receiving an ECD allograft.

PMID- 16570023
TI  - Birth cohort effect on the obesity epidemic in Denmark.
AB  - BACKGROUND: In Denmark, the obesity epidemic has developed in phases. To
      investigate if this has been a birth cohort phenomenon, we explored the secular
      trend in the prevalence of obesity among boys and young men. METHODS: We
      calculated body mass index (BMI; kg/m) over time for 163,835 Danish boys examined
      at ages 7-11 years and for 708,342 male draftees examined at age 19 years.
      Obesity was defined according to age-specific criteria for boys and as BMI >or=31
      kg/m for men. We examined trends in the prevalence of obesity from 1930 through
      1999, expressing time as the subjects' year of measurement and as year of birth.
      RESULTS: When expressed by year of measurement, 4 phases in the prevalence of
      obesity emerged for the boys and the young men, but they occurred at different
      times. However, when expressed by year of birth, the 2 stable periods and the 2
      periods with sharp increases in obesity occurred in the same birth years. An
      increased prevalence of obesity was identified for birth cohorts from the early
      1940s to the mid-1950s and from the late 1960s onward. CONCLUSIONS: The trends in
      the prevalence of obesity were similar in boys and young men only when expressed
      by year of birth, which suggests that early life may be a susceptible period for
      developing obesity. Specifically, the increased prevalence of obesity observed
      for birth cohorts from the early 1940s to the mid-1950s and from the late 1960s
      onward suggests that changes in the early life of these cohorts resulted in an
      increase in obesity at later ages.

PMID- 16570024
TI  - Maternal nutrient intakes and risk of orofacial clefts.
AB  - BACKGROUND: Information about nutritional factors as potential risks of orofacial
      clefts is limited. METHODS: In this population-based case-control study, we
      investigated whether periconceptional intakes of supplemental folic acid, dietary
      folate, and several other nutrients were associated with orofacial clefts. We
      included data on deliveries from 1997 through 2000 in the National Birth Defects
      Prevention Study. Orofacial cleft cases were infants or fetuses born with cleft
      palate (CP) or with cleft lip with or without cleft palate (CLP). Infants without
      malformations were eligible as controls. Interview participation was 71% among
      case mothers and 68% among control mothers. Interviews were completed for 704 CLP
      cases, 404 CP cases, and 2594 controls. RESULTS: The odds ratio (OR) for CLP
      associated with use of vitamin supplements containing folic acid was 0.88 (95%
      confidence interval = 0.73-1.07) and for CP was 1.09 (0.84-1.40). Adjusting for
      maternal race/ethnicity, age, and education produced an OR of 1.01 (0.82-1.24)
      for CLP and 1.02 (0.77-1.34) for CP. We found some evidence for decreased CLP
      risks (>or=30% reduction in risk) with increasing intakes of total protein,
      choline, and methionine. Decreased CP risk was associated with increased intake
      of cysteine. Intakes of only 2 micronutrients, iron and riboflavin, were found to
      reduce CLP risk when adjusted for other nutrients. CONCLUSION: Our observations
      contribute to the limited body of evidence suggesting a woman's periconceptional
      diet may influence clefting risks in her offspring. Our finding of no reduction
      in clefting risk with periconceptional use of supplements containing folic acid
      is inconsistent with many previous observations but not all.

PMID- 16570025
TI  - Maternal exposure to caffeine and risk of congenital anomalies: a systematic
      review.
AB  - BACKGROUND: Caffeine is teratogenic in animal studies when administered at high
      concentrations. Previous review articles have concluded that maternal caffeine
      consumption does not influence the risk of congenital anomalies. These reviews
      were narrative rather than systematic. The objective of the current systematic
      review is to provide a critical appraisal of epidemiologic evidence. METHODS: A
      search of the MEDLINE/PUBMED database (1966-October 2004) was conducted for all
      published epidemiologic studies with maternal intake of caffeine as an exposure
      and major malformations as an outcome. Study characteristics were abstracted,
      internal validity evaluated, and study findings summarized. RESULTS: Twenty-five
      papers met the initial criteria for inclusion, of which 18 were subsequently
      excluded as a result of other limitations. Effect estimates for the remaining 7
      studies were generally close to null. Specific subgroup analyses were summarized
      across studies (associations between coffee and cardiovascular malformations,
      coffee and oral clefts, and tea and cardiovascular malformations). Summary point
      estimates ranged from 1.0 to 1.2; the upper limits of all confidence intervals
      were less than 1.7. CONCLUSIONS: There is no evidence to support a teratogenic
      effect of caffeine in humans. Current epidemiologic evidence is not adequate to
      assess the possibility of a small change in risk of congenital anomalies
      resulting from maternal caffeine consumption.

PMID- 16570026
TI  - Vulnerability to heat-related mortality: a multicity, population-based, case
      crossover analysis.
AB  - BACKGROUND: Although studies have documented increased mortality during heat
      waves, little information is available on the subgroups most susceptible to these
      effects. We evaluated the effects of summertime high temperature on daily
      mortality among population subgroups defined by demographic characteristics,
      socioeconomic status, and episodes of hospitalization for various conditions
      during the preceding 2 years. METHODS: We studied a total of 205,019 residents of
      4 Italian cities (Bologna, Milan, Rome, and Turin) age 35 or older who died
      during 1997-2003. The case-crossover design was applied to evaluate the
      association between mean apparent temperature (same and previous day) and all
      cause mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) of
      dying at 30 degrees C (apparent temperature) relative to 20 degrees C were
      estimated accounting for time, population changes, and air pollution. RESULTS: We
      found an overall OR of 1.34 (CI = 1.27-1.42) at 30 degrees C relative to 20
      degrees C. The odds ratio increased with age and was higher among women (OR =
      1.45; 1.37-1.52) and among widows and widowers (1.50; 1.33-1.69). Low area-based
      income modestly increased the effect. Among the preexisting medical conditions
      investigated, effect modification was detected for previous psychiatric disorders
      (1.69; 1.39-2.07), depression (1.72; 1.24-2.39), heart conduction disorders
      (1.77; 1.38-2.27), and circulatory disorders of the brain (1.47; 1.34-1.62).
      Temperature-related mortality was higher among people residing in nursing homes,
      and a large effect was also detected for hospitalized subjects. CONCLUSIONS:
      Subsets of the population that are particularly vulnerable to high summer
      temperatures include the elderly, women, widows and widowers, those with selected
      medical conditions, and those staying in nursing homes and healthcare facilities.

PMID- 16570027
TI  - Apgar scores and long-term risk of epilepsy.
AB  - BACKGROUND: Low Apgar scores are associated with high risk of neonatal death,
      cerebral palsy, and mental retardation, but the association between Apgar scores
      and long-term risk of epilepsy remains unresolved. METHODS: We carried out a
      population-based cohort study of 1,538,732 live newborns in Denmark between 1
      January 1978 and 31 December 2002 by using national registers. The Apgar scores
      at 1 or 5 minutes were recorded by midwives following standardized procedures. We
      obtained information on epilepsy by linking the cohort with the National Hospital
      Register. Cohort members were followed from birth until onset of epilepsy, death,
      emigration, or 31 December 2002, whichever came first. RESULTS: The incidence
      rate of epilepsy increased consistently with decreasing Apgar scores. The
      incidence rate of epilepsy was 628 per 100,000 person-years for those with 5
      minute Apgar scores of 1 to 3 and 86 per 100,000 person-years for those with a
      score of 10; the resulting incidence rate ratio was 7.1 (95% confidence interval
      = 5.8-8.8). The incidence rate ratios of epilepsy associated with low Apgar
      scores were particularly high in early childhood but remained high into
      adulthood. The association did not change after excluding children with cerebral
      palsy, congenital malformations, or a parental history of epilepsy. CONCLUSIONS:
      Neonates with a suboptimal Apgar score have a higher risk of epilepsy that lasts
      into adult life. These findings suggest that prenatal or perinatal factors play a
      larger role in the etiology of epilepsy than has previously been recognized.

PMID- 16570028
TI  - Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular
      mortality.
AB  - BACKGROUND: Experimental data suggest that zinc, copper, and magnesium are
      involved in carcinogenesis and atherogenesis. Few longitudinal studies have
      related these minerals to cancer or cardiovascular disease mortality in a
      population. METHODS: Data from the Paris Prospective Study 2, a cohort of 4035
      men age 30-60 years at baseline, were used to assess the association between
      serum zinc, copper, and magnesium and all-cause, cancer, and cardiovascular
      disease mortality. Serum mineral values measured at baseline were divided into
      quartiles and classified into low (1st quartile, referent group), medium (2nd-3rd
      quartiles), and high (4th quartile) values. During 18-year follow up, 339 deaths
      occurred, 176 as a result of cancer and 56 of cardiovascular origin. Relative
      risks (RRs) for each element were inferred using Cox's proportional hazard model
      after controlling for various potential confounders. RESULTS: High copper values
      (4th quartile) were associated with a 50% increase in RRs for all-cause deaths
      (RR = 1.5; 95% confidence interval = 1.1-2.1), a 40% increase for cancer
      mortality (1.4; 0.9-2.2), and a 30% increase for cardiovascular mortality (1.3;
      0.6-2.8) compared with low values (1st quartile). High magnesium values were
      negatively related to mortality with a 40% decrease in RR for all-cause (0.6; 0.4
      0.8) and cardiovascular deaths (0.6; 0.2-1.2) and by 50% for cancer deaths (0.5;
      0.3-0.8). Additionally, subjects with a combination of low zinc and high copper
      values had synergistically increased all-cause (2.6; 1.4-5.0) and cancer (2.7;
      1.0-7.3) mortality risks. Similarly, combined low zinc and high magnesium values
      were associated with decreased all-cause (0.2; 0.1-0.5) and cancer (0.2; 0.1-0.8)
      mortality risks. CONCLUSIONS: High serum copper, low serum magnesium, and
      concomitance of low serum zinc with high serum copper or low serum magnesium
      contribute to an increased mortality risk in middle-aged men.

PMID- 16570029
TI  - Postoperative monitoring: principles, organization and quality of care.
      Definition of risk, evidence-based medicine, audit and quality of care.

PMID- 16570030
TI  - Interfacing spontaneous breathing and mechanical ventilation. New insights.
AB  - Mechanical ventilation (MV) with positive pressure insufflations of gas into the
      lung may be required to ensure sufficient oxygenation of blood and elimination of
      carbon dioxide in acute respiratory failure. Interfacing spontaneous breathing
      and mechanical ventilation has been used to improve gas exchange and may offer
      other advantages regarding integrity of lung tissue. Airway pressure release
      ventilation (APRV), or bilevel positive airway pressure (BiPAP), is a mechanical
      ventilatory mode with a low respiratory rate upon which spontaneous breaths can
      be superimposed during any time of the respiratory cycle. The mechanical pressure
      variations cause inflation and deflation of the lungs and the spontaneous breaths
      are added according to the demand of the respiratory center and neuromuscular
      function. This technique improves oxygenation of blood compared to MV alone. This
      seems to be caused by recruitment of collapsed lung tissue and increased aeration
      of the lung. Moreover, ventilation is distributed more to the dependent (dorsal
      in supine position) regions than with mechanical ventilation alone. Since blood
      flow goes preferentially to the dependent regions, the altered ventilation
      distribution results in improved matching of ventilation and perfusion, further
      enhancing or facilitating gas exchange. Moreover, there is less cyclic collapse,
      i.e. less re-collapse during expiration and reopening during inspiration than
      with MV alone. Further development of the interfacing technique can be expected,
      with synchronization and also dosing of the mechanical support and with
      triggering of the ventilator that is based on neural recordings rather than
      mechanical signals as pressure and flow.

PMID- 16570031
TI  - Microcirculatory alterations in critically ill patients.
AB  - The recent onset of orthogonal polarization spectral (OPS) imaging techniques has
      allowed the direct visualization of the microcirculation at the bedside of
      critically ill patients. A systematic review with particular emphasis on recent
      findings and implications in pathophysiological processes is presented. Using OPS
      techniques various investigators have observed microcirculatory alterations in
      critically ill patients, and especially in patients with severe sepsis and septic
      shock. These alterations include a decrease in vessel density and an increased
      proportion of non perfused or intermittently perfused capillaries, and these
      alterations can be fully reversed by the topical application of acetylcholine.
      Similar alterations are observed in patients with septic and cardiogenic shock.
      Persistent microvascular alterations are associated with the development of organ
      failure and death. In addition, the reversal of these alterations during
      resuscitation procedures is highly predictive of outcome. Unfortunately, the
      effects of many therapeutic interventions usually performed in critically ill
      patients are still not well defined, even though evidence coming from animal
      experiments is sometimes available. In particular, the role of fluid
      resuscitation, red blood cell transfusions, inotropic, vasoactive and anesthetic
      agents should be investigated. Microcirculation plays an important role in the
      pathogenesis of shock and organ dysfunction, especially in sepsis. The
      microcirculatory effects of various therapeutic interventions have still to be
      reported. OPS technique may become a valuable tool to monitor patients with
      circulatory failure.

PMID- 16570032
TI  - Non-invasive cardiac monitoring by aortic blood flow determination in patients
      undergoing hyperthermic intraperitoneal intraoperative chemotherapy.
AB  - AIM: The aim of this study was to evaluate the haemodynamic changes in patients
      undergoing cytoreductive surgery and intraperitoneal hyperthermic chemotherapy
      (IPHC) using an echo-Doppler device (Hemosonic 100). METHODS:  EXPERIMENTAL
      DESIGN: haemodynamic and cardiac function variables during IPHC, using a closed
      abdomen technique, were measured with the use of a non-invasive esophageal echo
      Doppler monitor. SETTING: operating room in an oncologic surgery department in
      hospital. Fifteen patients, ASA II or III with age ranging from 59 to 66 years
      were successively studied. All patients were under general anaesthesia with
      sevoflurane, remifentanil as titrated infusion, and cisatracurium for muscle
      relaxation. The standard monitoring included ECG, capnometry, invasive
      measurement of blood pressure and central venous pressure, pulsoximetry,
      diuresis, esophageal and tympanic temperature. Haemodynamic changes evaluated by
      an echo-Doppler device were recorded at predetermined times. RESULTS: A
      significant reduction in stroke volume (SV) and aortic blood flow (ABF) values
      was recorded (P<0.05) during the abdominal cavity filling, followed by a
      significant increase in total systemic vascular resistance values (P<0.05). A
      significant increase in SV, ABF and left ventricular ejection time was recorded
      90 min after the start of IPHC procedure (P<0.05) when the body temperature
      increased. Peak velocity and acceleration values increased significantly at the
      same time. CONCLUSIONS: These results suggest that the echo-Doppler device
      (Hemosonic 100) provided an easy-to-handle, non-invasive and reliable tool to
      monitor changes in cardiac parameters during IPHC.

PMID- 16570034
TI  - Surgical and anesthesiological procedures and patients outcome in a major
      teaching hospital, in a major non-teaching hospital and in a minor hospital.
AB  - AIM: This study was carried out to evaluate the outcome of patients in different
      hospitals with the aim to plan future structural and management changes. METHODS:
      All the anaesthesiological and surgical procedures were observed for a 2 weeks
      period in a major teaching hospital (A), in a major nonteaching hospital (B) and
      in a minor nonteaching hospital (C) in all the patients requiring anaesthesia.
      The main and the co-existing diseases and the surgical and anaesthesiological
      treatments they received were evaluated to determine the outcome. The ASA class,
      the duration of the procedure, the length of staying in hospital, the
      transfusions of blood or derivatives, the adverse events for each patient were
      also observed. RESULTS: The results showed that the patients admitted to the
      teaching hospital were classified in higher ASA risk classes and had surgery of
      longer duration, with a higher ratio of major surgery. The outcome was
      satisfactory in all the 3 hospitals, with a 2 days length of stay respectively in
      30% (A and B) and 50% (C) of the patients. The rate of mortality was low: only 3
      patients in hospital A and no patient in B and C died in a period of 2 days
      following surgery. Hospitals B and C showed a large use of modern techniques such
      as autologous blood transfusion and central and peripheral anaesthetic blocks,
      with a better cost-benefit ratio than the major teaching hospital. CONCLUSIONS:
      This study showed good results, but it should be repeated in a few years in order
      to evaluate any change and possible improvement in the management and outcome of
      the patients.

PMID- 16570033
TI  - Levobupivacaine and ropivacaine in the infraclavicular brachial plexus block.
AB  - AIM: Infraclavicular brachial plexus block were first described by Raj, yet this
      block remained underutilized despite theoretical advantages. The aim of this
      prospective, randomized study was to compare equipotent doses of levobupivacaine
      and ropivacaine. METHODS: For this prospective, randomized study we have
      enrolled, after informed consent, 30 patients of both sexes, ASA status I-II, who
      were going to receive surgery to the forearm or hand with tourniquet position on
      the arm. The infraclavicular plexus block was performed by using vertical
      technique. The block was performed with 30 mL of levobupivacaine 0.5% or
      ropivacaine 0.75%. RESULTS: No differences were reported between 2 groups in
      terms of demographic data. The onset-time for motor block was greater for
      ropivacaine group (p<0.05); the sensitive block was longer in levobupivacaine
      group (p<0.05). CONCLUSIONS: The long duration of sensory block associated with
      the with good analgesia, less toxicity and the pharmacodynamic properties of
      levobupivacaine include this new local anaesthetic as a valid choice respect
      other local anaesthetic for infraclavicular plexus block.

PMID- 16570035
TI  - Severe traumatic brain injury: management and prognosis.
AB  - AIM: The aim of the study is to assess the efficacy of early treatment in severe
      traumatic brain injury by evaluating patients' survival and functional recovery.
      METHODS: We subdivided 184 patients into 2 groups (Group A: patients admitted to
      hospital within the first hour of injury; Group B: patients admitted after the
      first hour of injury). In order to maintain the mean arterial pressure (MAP) >90
      with cerebral perfusion pressure (CPP) >70 mmHg, we used plasma expanders; in 76
      patients with MAP >90 mmHg, we administered dopamine, and in 5 cases
      noradrenaline. In 157 patients we used mechanical ventilation (MV). For
      orotracheal intubation and sedation/analgesia, we administered: propofol (a bolus
      of 2 mg/kg+1 mg/kg/h)+midazolam (0.03 mg/kg/h) + cisatracurium besilate (0.2
      mg/kg) in 113 patients, or thiopentone sodium (a bolus of 4 mg/kg + 1-2
      mg/kg/h)+cisatracurium besilate (0.2 mg/kg) in 44 patients with endocranial
      hypertension without bleeding and convulsions. After muscle relaxation we
      administered remifentanyl (0.075 microg/kg/min). Surgical decompression was
      performed in 57 cases. Data were analysed with Student's t-test. RESULTS: The
      number of deaths was significantly lower in Group A (P<0.05): 9 patients from
      Group A and 21 patients from Group B died within 24 h (P<0.05), while 15 patients
      from Group A and 16 patients from Group B died after the first 24 h period. After
      the recovery of critical life functions, 53 patients from Group A and 34 patients
      from Group B were transferred to a medical ward (P<0.0001), while 15 patients
      from Group A and 21 patients from Group B were transferred to a rehabilitation
      facility (P<0.05). CONCLUSIONS: Prevention, early treatment of complications and
      maintenance of homeostasis lead to a better prognosis in terms of survival,
      functional recovery and to a reduction in economic and social costs.

PMID- 16570036
TI  - Thymoglobulin-induced severe cardiovascular reaction and acute renal failure in a
      patient scheduled for orthotopic liver transplantation.
AB  - Antithymocyte globulin (ATG) has been shown to be effective as a pretreatment
      immunosuppressive agent in liver transplantation because of the ability to wean
      tacrolimus monotherapy after 4 months in pretreated recipients. However, the use
      of ATG can be complicated by serious side effects. Reported side effects include
      severe cardiopulmonary reactions, adult respiratory distress syndrome and
      hematological disorders. We report a case of a patient with a medical history of
      cirrhosis scheduled for orthotopic liver transplantation that, during the
      operation, showed swelling, hyperthermia, tachycardia and hypotension after the
      administration of ATG. Acute renal failure (ARF) was another serious side effect
      that our patient developed during ICU stay; we ascribed the occurrence of ARF to
      the serum sickness disease triggered by the ATG administration. Only one case has
      been reported of ARF after ATG-therapy before our experience. Therefore, severe
      hyperthermia and signs of cardiovascular dysfunction early after the beginning of
      ATG administration should be carefully evaluated and may need to consider the
      immediate ATG therapy withdrawal to prevent ARF.

PMID- 16570037
TI  - Purpura fulminans during meningococcal sepsis treated with Drotrecogin alpha. A
      clinical case.
AB  - A male patient, 29 years old, was admitted to our unit with purpura fulminans,
      coagulation deficiency, renal failure and subsequent septic shock accompanied by
      respiratory insufficiency in the absence of meningeal signs. The serum levels of
      endogenous protein C, ATIII and calcium were well below the norm. The
      bacteriological examination revealed the presence of gram-negative diplococci.
      The onset of adult respiratory distress syndrome (ARDS) revealed aa early
      complication of the meningococcal sepsis. Forty-eight hours after being admitted,
      the recombinant protein C infusion was started at a dose of 24 microg/kg/h for
      the duration of 96 h. The skin lesions regressed, starting from the ecchymosis
      and the edema of the face, trunk and auricular pavilions. A week after the onset
      of the symptomatology the chest X-ray appeared clear, the renal function had
      normalised, and the signs of shock had disappeared.

PMID- 16570038
TI  - Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric
      cancer.
AB  - A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral
      dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to
      determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting
      toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer
      (AGC). S-1 was administered orally at 80 mg m-2 day-1 from day 1 to 14 of a 28
      day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of
      70 mg m-2 day-1, stepping up to 100 mg m-2. The treatment was repeated every 4
      weeks, unless disease progression was observed. In the phase I portion, the MTD
      of CPT-11 was presumed to be 100 mg m-2, because 66.6% of patients (two of three)
      developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m-2)
      experienced grade 4 haematological or grade 3 nonhaematological toxicities at
      second course, followed by the dose reduction of CPT-11 from the third course.
      Considering safety and the ability to continue treatment, the final RD was
      determined to be 80 mg m-2. In the phase II portion, 42 patients including seven
      patients in the final RD phase I portion were evaluated. The median treatment
      course was five (range: 1-13). The incidences of severe (grade 3-4)
      haematological and nonhaematological toxicities were 19 and 10%, respectively,
      but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2
      76.6%), and the median survival time was 444 days. Our phase I/II trial showed S
      1 combined with CPT-11 is effective for AGC and is well tolerated, with
      acceptable toxicity.

PMID- 16570040
TI  - Mobile phone use and risk of acoustic neuroma: results of the interphone case
      control study in five North European countries.

PMID- 16570041
TI  - Mobile phone use and risk of acoustic neuroma.

PMID- 16570042
TI  - Mobile phone use and risk of acoustic neuroma: results of the interphone case
      control study in five north European countries [corrected].

PMID- 16570044
TI  - Co expression of SCF and KIT in gastrointestinal stromal tumours (GISTs) suggests
      an autocrine/paracrine mechanism.
AB  - KIT is a tyrosine kinase receptor expressed by several tumours, which has for
      specific ligand the stem cell factor (SCF). KIT is the main oncogene in
      gastrointestinal stromal tumours (GISTs), and gain-of-function KIT mutations are
      present in 70% of these tumours. The aim of the study was to measure and
      investigate the mechanisms of KIT activation in 80 KIT-positive GIST patients.
      KIT activation was quantified by detecting phosphotyrosine residues in Western
      blotting. SCF production was determined by reverse transcriptase-PCR, ELISA
      and/or immunohistochemistry. Primary cultures established from three GISTs were
      also analysed. The results show that KIT activation was detected in all cases,
      even in absence of KIT mutations. The fraction of activated KIT was not
      correlated with the mutational status of GISTs. Membrane and soluble isoforms of
      SCF mRNA were present in all GISTs analysed. Additionally, SCF was also detected
      in up to 93% of GISTs, and seen to be present within GIST cells. Likewise, the
      two SCF mRNA isoforms were found to be expressed in GIST-derived primary
      cultures. Thus, KIT activation in GISTs may in part result from the presence of
      SCF within the tumours.

PMID- 16570043
TI  - COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast
      cancer.
AB  - Increased expression of COX-2 or VEGF-C has been correlated with progressive
      disease in certain cancers. Present study utilized several human breast cancer
      cell lines (MCF-7, T-47D, Hs578T and MDA-MB-231, varying in COX-2 expression) as
      well as 10 human breast cancer specimens to examine the roles of COX-2 and
      prostaglandin E (EP) receptors in VEGF-C expression or secretion, and the
      relationship of COX-2 or VEGF-C expression to lymphangiogenesis. We found a
      strong correlation between COX-2 mRNA expression and VEGF-C expression or
      secretion levels in breast cancer cell lines and VEGF-C expression in breast
      cancer tissues. Expression of LYVE-1, a selective marker for lymphatic
      endothelium, was also positively correlated with COX-2 or VEGF-C expression in
      breast cancer tissues. Inhibition of VEGF-C expression and secretion in the
      presence of COX-1/2 or COX-2 inhibitors or following downregulation of COX-2 with
      COX-2 siRNA established a stimulatory role COX-2 in VEGF-C synthesis by breast
      cancer cells. EP1 as well as EP4 receptor antagonists inhibited VEGF-C production
      indicating the roles of EP1 and EP4 in VEGF-C upregulation by endogenous PGE2.
      Finally, VEGF-C secretion by MDA-MB-231 cells was inhibited in the presence of
      kinase inhibitors for Her-2/neu, Src and p38 MAPK, indicating a requirement of
      these kinases for VEGF-C synthesis. These results, for the first time,
      demonstrate a regulatory role of COX-2 in VEGF-C synthesis (and thereby
      lymphangiogenesis) in human breast cancer, which is mediated at least in part by
      EP1/EP4 receptors.

PMID- 16570046
TI  - Remission from Kaposi's sarcoma on HAART is associated with suppression of HIV
      replication and is independent of protease inhibitor therapy.
AB  - Highly active antiretroviral therapy (HAART) reduces the incidence and improves
      the prognosis of Kaposi's sarcoma (KS). This study was designed to identify
      factors associated with KS clinical responses in HIV-infected patients during
      HAART. We reviewed the files of 138 HIV-1-infected patients with KS.
      Epidemiologic and HIV-related clinical and biological parameters were recorded at
      KS diagnosis (baseline) and every 6 months thereafter. In a subset of 73
      antiretroviral-naive patients, we compared the clinical outcome of KS according
      to the use or nonuse of protease inhibitors (PI). After 6 months of follow-up, KS
      remission was more frequent in patients who were naive of HAART and who were at
      ACTG stage S0 at baseline (P = 0.03 and 0.02). Undetectable HIV viral load was
      strongly associated with KS remission (P< or = 0.004 at all time points), while
      CD4 cell count was not. Among the 73 antiretroviral-naive patients at baseline,
      and who were studied for 24 months, KS outcome did not differ between patients
      who were prescribed PI-containing and PI-sparing regimens. Intercurrent
      multicentric Castleman's disease was associated with poor outcome after 60 months
      of follow-up (P< or = 0.0001). Fourteen deaths occurred after a median follow-up
      of 37.5 months, eight of which were KS related. Suppression of HIV replication
      appears to be crucial to control KS. Non-PI-based regimens were equivalent to PI
      based regimens as regards the clinical and virological outcome of antiretroviral
      naive HIV-infected patients with KS.

PMID- 16570045
TI  - Cardiac toxicity of trastuzumab in metastatic breast cancer patients previously
      treated with high-dose chemotherapy: a retrospective study.
AB  - HER-2 overexpression is associated to a poor prognosis in high-risk and
      metastatic breast cancer (MBC) patients treated with high-dose chemotherapy
      (HDC). HER-2 status is also a predictive factor and when trastuzumab is
      administered in combination with or sequentially to chemotherapy, a significant
      disease-free and/or overall survival improvement has been observed in HER-2+
      early and MBC. Unfortunately, in both settings, trastuzumab is associated with an
      increased risk of cardiac dysfunction (CD). We have reviewed the clinical charts
      of HER-2-overexpressing MBC patients treated with trastuzumab after HDC. Age,
      baseline left ventricular ejection fraction (LVEF), radiation therapy on cardiac
      area, exposure to anthracycline, single or multiple transplant, high-dose agents,
      trastuzumab treatment duration were recorded as potential risk factors. In total,
      53 patients have been included in the analysis. Median LVEF at baseline was
      60.5%; at the end of trastuzumab (data available for 28 patients only), it was
      55% (P = 0.01). Five out of the 28 (17.9%) patients experienced CD. Two out of 53
      (3.8%) patients developed a congestive heart failure. Age > or = 50 years and
      multiple transplant procedure were potential risk factors for CD. The overall
      incidence of CD observed in this population of HER-2+ MBC patients treated with
      trastuzumab after HDC is not superior to that reported with concomitant
      trastuzumab and anthracyclines. However, patients with age > or = 50 years or
      receiving multiple course of HDC should be considered at risk for CD.

PMID- 16570047
TI  - Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal
      cancer.
AB  - Erlotinib (Tarceva, OSI-774), a potent epidermal growth factor receptor tyrosine
      kinase inhibitor (EGFR), was evaluated in a phase II study to assess its activity
      in patients with metastatic colorectal cancer. In all, 38 patients with
      metastatic colorectal cancer were treated with erlotinib at a continuous daily
      oral dose of 150 mg. Radiological evaluation was carried out every 8 weeks and
      tumour biopsies were performed before treatment and on day 8. Of 31 evaluable
      patients, 19 (61%) had progressive disease and 12 (39%) had stable disease
      (s.d.). The median time to progression for those patients having s.d. was 123
      days (range 108-329 days). The most common adverse events were rash in 34
      patients and diarrhoea in 23 patients. Correlative studies were conducted to
      investigate the effect of erlotinib on downstream signalling. Tumour tissue
      correlations were based on usable tissue from eight match paired tumour samples
      pre- and on therapy, and showed a statistically significant decrease in the
      median intensity of both pEGFR (P=0.008) and phospho-extracellular signal
      regulated kinase (ERK) (P=0.008) a week after commencement of treatment. No other
      statistically significant change in tumour markers was observed. Erlotinib was
      well tolerated with the most common toxicities being rash and diarrhoea. More
      than one-third of evaluable patients had s.d. for a minimum of 8 weeks.
      Correlative studies showed a reduction in phosphorylated EGFR and ERK in tumour
      tissue post-treatment.

PMID- 16570048
TI  - Adiponectin and cancer: a systematic review.
AB  - Recent studies have demonstrated that obesity is a significant risk factor for
      the development of several malignancies, but the mechanisms underlying this
      relationship remain to be fully elucidated. Adiponectin, an adipocyte secreted
      endogenous insulin sensitizer, appears to play an important role not only in
      glucose and lipid metabolism but also in the development and progression of
      several obesity-related malignancies. In this review, we present recent findings
      on the association of adiponectin with several malignancies as well as recent
      data on underlying molecular mechanisms that provide novel insights into the
      association between obesity and cancer risk. We also identify important research
      questions that remain unanswered.

PMID- 16570049
TI  - Lack of evidence of disease contamination in ovarian tissue harvested for
      cryopreservation from patients with Hodgkin lymphoma and analysis of factors
      predictive of oocyte yield.
AB  - Ovarian cryopreservation is a promising technique to preserve fertility in women
      with Hodgkin lymphoma (HL) treated with chemotherapy. Thus, the aim of this study
      was to examine harvested ovarian tissue for subclinical involvement by HL by
      morphology/immunohistochemistry, and to define patient and treatment factors
      predictive of oocyte yield. This was a retrospective analysis of 26 ovarian
      tissue samples harvested for cryopreservation from women with HL. Histology,
      immunohistochemistry and follicle density (number mm(-3)) was examined. Disease
      status and preharvest chemotherapy details were obtained on 24 patients. The
      median age was 22 years (range 13-29). Seven of 24 patients had
      infradiaphragmatic disease at time of harvest. Nine of 20 patients had received
      chemotherapy preharvest (ABVD (Adriamycin), Bleomycin, Vinblastine and
      Dacarbazine) = 7, other regimens = 2). The seven receiving ABVD showed no
      difference in follicle density compared to patients not receiving treatment (n =
      14); (median = 1555 vs 1620 mm3 P = 0.97). Follicle density measurement showed no
      correlation with patient age (R2 = 0.0001, P = 0.99). There was no evidence of HL
      involvement in the 26 samples examined (95% CI = 0-11%). In conclusion,
      subclinical involvement of HL has not been identified in ovarian tissue, even
      when patients have infradiaphragmatic disease. Furthermore, the quality of tissue
      harvested does not appear to be adversely affected by patient's age or prior ABVD
      chemotherapy.

PMID- 16570050
TI  - Expression of ADAMTS-8, a secreted protease with antiangiogenic properties, is
      downregulated in brain tumours.
AB  - Angiogenesis and extracellular matrix degradation are key events in tumour
      progression, and factors regulating stromal-epithelial interactions and matrix
      composition are potential targets for the development of novel anti
      invasive/antiangiogenic therapies. Here, we examine the expression of ADAMTS-8, a
      secreted protease with antiangiogenic properties, in brain tissues. Using
      quantitative RT-polymerase chain reaction (PCR), high, equivalent expression of
      ADAMTS-8 was found in normal whole brain, cerebral cortex, frontal lobe,
      cerebellum and meninges. ADAMTS-8 expression in 34 brain tumours (including 22
      high-grade gliomas) and four glioma cell lines indicated at least two-fold
      reduction in mRNA compared to normal whole brain in all neoplastic tissues, and
      no detectable expression in 14 out of 34 (41%) tumours or four out of four (100%)
      cell lines. In contrast, differential expression of TSP1 and VEGF was seen in
      nine out of 15 (60%) and seven out of 13 (54%) tumours, with no relationship in
      the expression of these genes. Immunohistochemistry and Western analysis
      indicated downregulation of ADAMTS-8 protein in >77% tumours. Methylation
      specific PCR analysis of ADAMTS-8 indicated promoter hypermethylation in one out
      of 24 brain tumours (a metastasis) and three out of four glioma cell lines
      suggesting an alternative mechanism of downregulation. These data suggest a role
      for ADAMTS-8 in brain tumorigenesis, warranting further investigation into its
      role in regulation of tumour angiogenesis and local invasion.

PMID- 16570052
TI  - The advocates.

PMID- 16570051
TI  - Epoetin alfa in platinum-treated ovarian cancer patients: results of a
      multinational, multicentre, randomised trial.
AB  - This multicentre, open-label, controlled clinical trial assessed the effects of
      epoetin alfa treatment on haematologic and quality of life (QOL) parameters in
      182 anaemic (Hb< or = 12 g dl(-1)) ovarian cancer patients receiving platinum
      chemotherapy. Patients were randomised 2 : 1 to receive epoetin alfa 10,000-20
      000 IU three times weekly plus best standard treatment (BST) or BST only. Main
      study end points were changes from baseline in haemoglobin (Hb) level,
      transfusion requirements, and QOL. For the epoetin alfa group, mean Hb increased
      by 1.8 g dl(-1) by weeks 4-6 and was significantly increased from baseline
      through study end (P<0.001). The mean change in Hb from baseline was
      significantly (P<0.001) greater for epoetin alfa than BST patients at all post
      baseline evaluations. Significantly fewer epoetin alfa than BST patients required
      transfusion(s) after the first 4 weeks of treatment (7.9 vs 30.5%; P<0.001).
      Also, significant (P< or = 0.04) differences favouring the epoetin alfa group
      over the BST group were found for all three median CLAS scores (Energy Level,
      Ability to Do Daily Activities, Overall QOL) and the median average CLAS score
      during chemotherapy. These findings support use of epoetin alfa to increase Hb
      levels, reduce transfusion use, and improve QOL in anaemic ovarian cancer
      patients receiving platinum chemotherapy.

PMID- 16570054
TI  - Explaining the biological activity of transactivation-deficient p53 variants.

PMID- 16570056
TI  - Enrichment of regulatory motifs upstream of predicted DAF-16 targets.

PMID- 16570058
TI  - Skin barrier function and allergic risk.

PMID- 16570059
TI  - A sweet link between TGFbeta and vascular disease?

PMID- 16570060
TI  - Clonal diversity in tumor progression.

PMID- 16570061
TI  - A key stone cop regulates oxalate homeostasis.

PMID- 16570062
TI  - A simple recipe for drug interaction networks earns its stars.

PMID- 16570066
TI  - The role of geographic setting on the diversification process among Tephritis
      conura (Tephritidae) host races.
AB  - We address the controversy over the processes causing divergence during
      speciation. Host races of the fruit fly Tephritis conura attack the thistles
      Cirsium oleraceum and Cirsium heterophyllum. By studying the genetic divergence
      of T. conura in areas where host plants are sympatric, parapatric and allopatric,
      we assessed the contribution of geography in driving host-race divergence. We
      also evaluated the relative importance of genetic drift and selection in the
      diversification process, by analysis of the geographic distribution of genetic
      variation. Host races were significantly diverged at five out of 13 polymorphic
      allozyme loci. Variance at two loci, Hex and Pep D, was almost exclusively
      attributable to host-plant affiliation in all geographic settings. However, Hex
      was significantly more differentiated between host races in sympatry/parapatry
      than in allopatry. This result might be explained by selection against
      hybridisation or against incorrect host choice in contact areas. Linkage
      disequilibrium tests suggest the latter: gene flow in contact areas may occur
      from males of the host-race C. heterophyllum to females of the host-race C.
      oleraceum, whereas incorrect oviposition events were never observed. The
      distinctive patterns of genetic differentiation at the two highly differentiated
      loci implicate the action of selection (acting directly or on linked loci) rather
      than genetic drift. Despite their restricted interactions in sympatry, we
      conclude that host races are stable and that the major diversification process
      took place before species arrived in today's geographical settings.

PMID- 16570067
TI  - Distribution and genetic variation of Reticulitermes (Isoptera: Rhinotermitidae)
      in Portugal.
AB  - The genus Reticulitermes has a Holartic distribution and is widely represented in
      southern Europe. It is established in Portugal, across the full range of ambient
      environmental conditions, using different types of wood resources, as available,
      and nesting ubiquitously in many types of soil. Sequencing of part of the mtDNA
      COII gene revealed that all the specimens sampled on a north-south transect of
      the country were Reticulitermes grassei (considered synonymous with R. lucifugus
      grassei). Nevertheless, an association between the genetic and the geographical
      distances of sampled specimens was shown, leading to the conclusion that discrete
      termite populations have differentiated in situ. The geographic component of the
      genetic polymorphism should be the subject for further research.

PMID- 16570068
TI  - Quantitative genetics of preference and performance on chickpeas in the noctuid
      moth, Helicoverpa armigera.
AB  - If a novel, resistant host-plant genotype arises in the environment, insect
      populations utilising that host must be able to overcome that resistance in order
      that they can maintain their ability to feed on that host. The ability to evolve
      resistance to host-plant defences depends upon additive genetic variation in
      larval performance and adult host-choice preference. To investigate the potential
      of a generalist herbivore to respond to a novel resistant host, we estimated the
      heritability of larval performance in the noctuid moth, Helicoverpa armigera, on
      a resistant and a susceptible variety of the chickpea, Cicer arietinum, at two
      different life stages. Heritability estimates were higher for neonates than for
      third-instar larvae, suggesting that their ability to establish on plants could
      be key to the evolution of resistance in this species; however, further
      information regarding the nature of selection in the field would be required to
      confirm this prediction. There was no genetic correlation between larval
      performance and oviposition preference, indicating that female moths do not
      choose the most suitable plant for their offspring. We also found significant
      genotype by environment interactions for neonates (but not third-instar larvae),
      suggesting that the larval response to different plant genotypes is stage
      specific in this species.

PMID- 16570069
TI  - Genetics of divergence in male wing pigmentation and courtship behavior between
      Drosophila elegans and D. gunungcola.
AB  - Many sex-specific traits involved in mating consist of functionally coordinated
      morphologies and behaviors. How the components of these complex traits evolve and
      become coordinated during evolution is unknown. In order to understand how such
      trait complexes evolve and diversify, we must decipher the genetic underpinnings
      of their components. In this study, we begin to elucidate the genetic
      architecture underlying differences in functionally related male pigmentation and
      behavior between two Asian Drosophila melanogaster group species, D. elegans and
      D. gunungcola. D. elegans possesses a male-specific wing melanin spot and a
      stereotypical wing display element in male courtship, whereas D. gunungcola lacks
      both of these traits. Using reciprocal F1 male hybrids, we demonstrate that the X
      chromosome contains a major locus or loci required for wing spot formation and
      that autosomal loci largely determine the male courtship display. Using
      phenotypic and genetic analysis of backcross progeny, we further demonstrate that
      both the wing spot and courtship differences between the two species are
      polygenic and both depend at least in small part on genetic factors on both the X
      and the autosomes. Finally, we find that male wing spot size and courtship wing
      display are highly correlated in backcross progeny, suggesting that linkage or
      pleiotropy may have been involved in their coordinated evolution.

PMID- 16570070
TI  - Molecular genetics: Bloodthirsty amazons?

PMID- 16570071
TI  - Evolutionary Genetics: is brain evolution still continuing in modern humans?

PMID- 16570072
TI  - Interstitial 9q22.3 microdeletion: clinical and molecular characterisation of a
      newly recognised overgrowth syndrome.
AB  - In the course of a systematic whole genome screening of patients with unexplained
      overgrowth syndrome by microarray-based comparative genomic hybridisation (array
      CGH), we have identified two children with nearly identical 6.5 Mb-long de novo
      interstitial deletions at 9q22.32-q22.33. The clinical phenotype includes
      macrocephaly, overgrowth and trigonocephaly. In addition, both children present
      with psychomotor delay, hyperactivity and distinctive facial features. Further
      analysis with a high-resolution custom microarray covering the whole breakpoint
      intervals with fosmids mapped the deletion breakpoints within 100-kb intervals:
      although the deletion boundaries are different for the two patients, nearly the
      same genes are deleted in both cases. We suggest therefore that microdeletion of
      9q22.32-q22.33 is a novel cause of overgrowth and mental retardation. Its
      association with distinctive facial features should help in recognising this
      novel phenotype.

PMID- 16570073
TI  - Haplotype-based association analysis of 56 functional candidate genes in the IBD6
      locus on chromosome 19.
AB  - Evidence from four independent linkage studies and two meta-analyses of genome
      wide data support the existence of a locus conferring susceptibility to
      inflammatory bowel diseases (IBD) in chromosomal region 19p. Identification of a
      susceptibility allele in this approximately 28.5 Mb region with over 600 genes is
      a formidable task. To tackle this problem, we undertook two approaches: (1)
      haplotype-based candidate-gene screen, and (2) evaluation of previously reported
      associations. For the former, we selected genes with potential implication in IBD
      pathogenesis based on published functional and expression data, typed SNPs,
      constructed haplotypes, screened for association in 180 IBD trios, and followed
      up preliminary associations in 343 IBD patients and 207 control individuals.
      Overall, we analyzed 465 SNPs, and 260 haplotypes distributed across 56 candidate
      genes. We found suggestive evidence of association (nominal P<0.01) with four
      genes (C3, FCER2, IL12RB1, and CRLF1) in a screening stage, but were unable to
      confirm these preliminary observations at follow-up. In the second approach, we
      typed four nonsynonymous polymorphisms in genes C3 (R102G and L314P) and ICAM1
      (G241R and K469E) in four independent cohorts totaling 2178 IBD cases. We
      evaluated these data together with previously published reports for three of
      these variants (C3-Gly102, ICAM1-Arg241, and ICAM1-Glu469), in a meta-analysis.
      Our pooled meta-analysis provides compelling evidence against association of
      these variants with disease. Overall, we performed the most comprehensive
      candidate-gene association study for IBD to date. The information hereby
      generated constitutes a valuable resource to investigate other common genetic
      immune diseases, such as celiac disease.

PMID- 16570074
TI  - SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with
      enlarged vestibular aqueduct in Caucasian populations.
AB  - Sensorineural hearing loss is the most frequent sensory deficit of childhood and
      is of genetic origin in up to 75% of cases. It has been shown that mutations of
      the SLC26A4 (PDS) gene were involved in syndromic deafness characterized by
      congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as
      well as in congenital isolated deafness (DFNB4). While the prevalence of SLC26A4
      mutations in Pendred's syndrome is clearly established, it remains to be studied
      in large cohorts of patients with nonsyndromic deafness and detailed clinical
      informations. In this report, 109 patients from 100 unrelated families, aged from
      1 to 32 years (median age: 10 years), with nonsyndromic deafness and enlarged
      vestibular aqueduct, were genotyped for SLC26A4 using DHPLC molecular screening
      and sequencing. In all, 91 allelic variants were observed in 100 unrelated
      families, of which 19 have never been reported. The prevalence of SLC26A4
      mutations was 40% (40/100), with biallelic mutation in 24% (24/100), while six
      families were homozygous. All patients included in this series had documented
      deafness, associated with EVA and without any evidence of syndromic disease.
      Among patients with SLC26A4 biallelic mutations, deafness was more severe,
      fluctuated more than in patients with no mutation. In conclusion, the incidence
      of SLC26A4 mutations is high in patients with isolated deafness and enlarged
      vestibular aqueduct and could represent up to 4% of nonsyndromic hearing
      impairment. SLC26A4 could be the second most frequent gene implicated in
      nonsyndromic deafness after GJB2, in this Caucasian population.

PMID- 16570075
TI  - Protective effect of the 20-HETE inhibitor HET0016 on brain damage after
      temporary focal ischemia.
AB  - Cytochrome P450 metabolism of arachidonic acid produces the potent
      vasoconstrictive metabolite, 20-hydroxyeicosatetraenoic acid (20-HETE). Recent
      studies have implicated 20-HETE as a vasoconstrictive mediator in hemorrhagic
      stroke. The purpose of this study was to determine the effect of the 20-HETE
      inhibitor, HET0016, on lesion volume and cerebral blood flow (CBF) after
      temporary middle cerebral artery occlusion (MCAO) in rats. Plasma
      pharmacokinetics and tissue concentrations of HET0016 were determined after a 10
      mg/kg intraperitoneal dose. Separate rats were treated with HET0016 or vehicle
      before 90 mins of MCAO. Lesion volume was assessed by 2,3,5-triphenyl-tetrazolium
      chloride and cerebral flow was determined using laser Doppler flow. The effect of
      MCAO on in vitro microsomal formation of mono-oxygenated arachidonic acid
      metabolites was also determined. Results show that HET0016 has a short biologic
      half-life, distributes into the brain, and is associated with a 79.6% reduction
      in 20-HETE concentration in the cortex. Lesion volume was greatly reduced in
      HET0016-treated (9.1%+/-4.9%) versus vehicle-treated (57.4%+/-9.8%; n=6; P<0.001)
      rats. An attenuation of the observed decrease in CBF was observed in HET0016
      treated (180 mins 89.2%+/-6.2%; 240 mins 88.1%+/-5.7% of baseline flow) versus
      vehicle control (180 mins 57.6%+/-19.0%; 240 mins 53.8%+/-20.0% of baseline flow;
      n=6; P<0.05). Brain cortical microsomal formation rate of 20-HETE was also
      reduced at 24 h in the ipsilateral hemisphere after MCAO. These data support a
      significant role for 20-HETE in the pathogenesis of ischemic stroke.

PMID- 16570076
TI  - Promoter region methylation and reduced expression of thrombospondin-1 after
      oxygen-glucose deprivation in murine cerebral endothelial cells.
AB  - Angiogenesis is induced in response to ischemia. Thrombospondin-1 (TSP-1) is a
      potent angiostatic factor. Silencing of TSP-1 expression may contribute to the
      postischemic angiogenesis. Upregulation of TSP-1, in contrast, may terminate the
      postischemic angiogenesis. A possible mechanism that silences TSP-1 expression is
      the DNA methylation of its promoter region. DNA methylation has been reported
      following cerebral ischemia. The present study aimed to explore whether
      methylation of the promoter region of TSP-1 regulates its expression after oxygen
      glucose deprivation (OGD) in murine cerebral endothelial cells (CECs) in vitro.
      Sublethal OGD increased the extent of methylation of the promoter region of TSP-1
      with a concurrent decrease in TSP-1 mRNA and protein expression in CECs. After
      reoxygenation, demethylation of the TSP-1 promoter region led to the restoration
      of TSP-1 mRNA and protein expression. The extent of methylation of the promoter
      region of TSP-1 was inversely correlated with the extent of TSP-1 gene expression
      at mRNA and protein levels after OGD. Oxygen-glucose deprivation-induced
      reduction in the TSP-1 mRNA level was not accompanied by a change in mRNA
      stability. These findings raise the possibility that OGD downregulation of TSP-1
      expression is at least in part due to methylation of its promoter region.

PMID- 16570077
TI  - Activation of calcium/calmodulin-dependent protein kinases after traumatic brain
      injury.
AB  - A prominent cognitive impairment after traumatic brain injury (TBI) is
      hippocampal-dependent memory loss. Although the histopathologic changes in the
      brain are well documented after TBI, the underlying biochemical mechanisms that
      contribute to memory loss have yet to be thoroughly delineated. Thus, we
      determined if calcium/calmodulin-dependent protein kinases (CaMKs), known to be
      necessary for the formation of hippocampal-dependent memories, are regulated
      after TBI. Sprague-Dawley rats underwent moderate parasagittal fluid-percussion
      brain injury on the right side of the parietal cortex. The ipsilateral
      hippocampus and parietal cortex were Western blotted for phosphorylated,
      activated alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII),
      CaMKIV, and CaMKI. alpha-Calcium/calmodulin-dependent protein kinase II was
      activated in membrane subcellular fractions from the hippocampus and parietal
      cortex 30 mins after TBI. CaMKI and CaMKIV were activated in a more delayed
      manner, increasing in phosphorylation 1 h after TBI. The increase in activated
      alpha-CaMKII in membrane fractions was accompanied by a decrease in cytosolic
      total alpha-CaMKII, suggesting redistribution to the membrane. Using confocal
      microscopy, we observed that alpha-CaMKII was activated within hippocampal
      neurons of the dentate gyrus, CA3, and CA1 regions. Two downstream substrates of
      alpha-CaMKII, the AMPA-type glutamate receptor GluR1, and cytoplasmic
      polyadenylation element-binding protein, concomitantly increased in
      phosphorylation in the hippocampus and cortex 1 h after TBI. These results
      demonstrate that several of the biochemical cascades that subserve memory
      formation are activated unselectively in neurons after TBI. As memory formation
      requires activation of CaMKII signaling pathways at specific neuronal synapses,
      unselective activation of CaMKII signaling in all synapses may disrupt the
      machinery for memory formation, resulting in memory loss after TBI.

PMID- 16570078
TI  - Chromatin signatures of pluripotent cell lines.
AB  - Epigenetic genome modifications are thought to be important for specifying the
      lineage and developmental stage of cells within a multicellular organism. Here,
      we show that the epigenetic profile of pluripotent embryonic stem cells (ES) is
      distinct from that of embryonic carcinoma cells, haematopoietic stem cells (HSC)
      and their differentiated progeny. Silent, lineage-specific genes replicated
      earlier in pluripotent cells than in tissue-specific stem cells or differentiated
      cells and had unexpectedly high levels of acetylated H3K9 and methylated H3K4.
      Unusually, in ES cells these markers of open chromatin were also combined with
      H3K27 trimethylation at some non-expressed genes. Thus, pluripotency of ES cells
      is characterized by a specific epigenetic profile where lineage-specific genes
      may be accessible but, if so, carry repressive H3K27 trimethylation
      modifications. H3K27 methylation is functionally important for preventing
      expression of these genes in ES cells as premature expression occurs in embryonic
      ectoderm development (Eed)-deficient ES cells. Our data suggest that lineage
      specific genes are primed for expression in ES cells but are held in check by
      opposing chromatin modifications.

PMID- 16570079
TI  - A new look at bronchopulmonary dysplasia classification.

PMID- 16570080
TI  - Studying determinants of length of hospital stay.
AB  - Clinicians are accustomed to focusing on individual patients. However, when
      studying how long their patients stay in the hospital, the focus must widen.
      Length of stay summarizes the performance of the entire, exceedingly complex,
      NICU system. Ordinary statistical methods for modeling patient outcomes assume
      that what happens to one patient is unrelated to what happens to another.
      However, patients in the same NICU are exposed to similar hospital practices, so
      patient outcomes may be correlated. Length of stay data must be analyzed by
      methods that account for possibly correlated outcomes. In addition, to improve
      patient care and outcomes, predictive models must include determinants clinicians
      can influence. Such variables describe care process exposures, available beds,
      demand for beds, and staffing levels.

PMID- 16570081
TI  - Administration of rituximab during the first trimester of pregnancy without
      consequences for the newborn.
AB  - Rituximab, a chimeric mouse/human monoclonal antibody that binds to the CD20
      antigen, is part of current treatment of many B-cell malignancies and several
      autoimmune diseases. Very few cases of rituximab administration during pregnancy
      have been described. We report here the case of rituximab administration during
      the first trimester of pregnancy in a woman with autoimmune hemolytic anemia. No
      significant effects were observed in B-cell counts or the immune status of the
      newborn.

PMID- 16570082
TI  - Neonatal hypertrichosis in an infant of a diabetic mother with congenital
      hypothyroidism.
AB  - Hypertrichosis in a newborn girl infant of a diabetic mother with congenital
      hypothyroidism is reported. Both neonatal hyperinsulism and increased
      testosterone levels were documented. The hypertrichosis resolved after 3 months'
      of thyroxine replacement treatment. The possible causal association between
      hypothyroidism, and hypertrichosis has not been previously reported in neonatal
      period. Thyroid function should be evaluated in all newborn babies with
      hypertrichosis or abnormal distribution of body hair.

PMID- 16570083
TI  - Case report of Haddad syndrome in a newborn: congenital central hypoventilation
      syndrome and Hirschsprung's disease.
AB  - Congenital central hypoventilation syndrome (CCHS) is a rare disorder
      characterized by failure of automatic control of breathing. Diagnosis is made by
      exclusion of other causes of hypoventilation. Genetic etiology is strongly
      suspected. Other autonomic nervous system dysfunctions, tumors of neural crest
      origin and Hirschsprung's disease are often found in affected children.
      Association with Hirschsprung's disease is known as Haddad syndrome. We present a
      newborn with respiratory distress since birth and Hirschprung's disease
      subsequently diagnosed with Haddad syndrome.

PMID- 16570084
TI  - Commentary: screening as a tool for engagement.

PMID- 16570086
TI  - Interventions to prevent obesity in children and adolescents: a systematic
      literature review.
AB  - OBJECTIVE: Preventive measures to contain the epidemic of obesity have become a
      major focus of attention. This report reviews the scientific evidence for medical
      interventions aimed at preventing obesity during childhood and adolescence.
      DESIGN: A systematic literature review involving selection of primary research
      and other systematic reviews. Articles published until 2004 were added to an
      earlier (2002) review by the Swedish Council on Technology Assessment in Health
      Care. METHODS: Inclusion criteria required controlled studies with follow-up of
      at least 12 months and results measured as body mass index, skinfold thickness or
      the percentage of overweight/obesity. Children could be recruited from normal or
      high-risk populations. RESULTS: Combining the new data with the previous review
      resulted in an evaluation of 24 studies involving 25 896 children. Of these,
      eight reported that prevention had a statistically significant positive effect on
      obesity, 16 reported neutral results and none reported a negative result (sign
      test; P=0.0078). Adding the studies included in five other systematic reviews
      yielded, in total, 15 studies with positive, 24 with neutral and none with
      negative results. Thus, 41% of the studies, including 40% of the 33 852 children
      studied, showed a positive effect from prevention. These results are unlikely to
      be a random chance phenomenon (P=0.000061). CONCLUSION: Evidence shows that it is
      possible to prevent obesity in children and adolescents through limited, school
      based programs that combine the promotion of healthy dietary habits and physical
      activity.

PMID- 16570087
TI  - Body mass index in children and adolescents: considerations for population-based
      applications.

PMID- 16570088
TI  - Diagnostic accuracy of the BMI for age in paediatrics.

PMID- 16570089
TI  - Body fat reference curves for children.
AB  - OBJECTIVE: To refine the diagnosis of childhood obesity by creating new sex
      specific centile curves for body fat and to base these references on a simple and
      affordable method that could be widely adopted in clinical practice and surveys.
      DESIGN: Body fat was measured by bio-impedance in 1985 Caucasian children aged 5
      18 years from schools in Southern England. Smoothed centile charts were derived
      using the LMS method. RESULTS: The new body fat curves reflect the known
      differences in the development of adiposity between boys and girls. The curves
      are similar by sex until puberty but then diverge markedly, with males
      proportionately decreasing body fat and females continuing to gain. These sex
      differences are not revealed by existing curves based on body mass index. We
      present charts in which cutoffs to define regions of 'underfat', 'normal',
      'overfat' and 'obese' are set at the 2nd, 85th and 95th centiles. These have been
      designed to yield similar proportions of overweight/overfat and obese children to
      the IOTF body mass index cutoffs. CONCLUSIONS: Direct assessment of adiposity,
      the component of overweight that leads to pathology, represents a significant
      advance over body mass index. Our new charts will be published by the Child
      Growth Foundation for clinical monitoring of body fat, along with the software to
      convert individual measurements to Z-scores.

PMID- 16570090
TI  - Overweight and obesity prevalence in children based on 6- or 12-month IOTF cut
      points: does interval size matter?
AB  - The International Obesity Taskforce (IOTF) recommends using age- and gender
      specific body mass index (BMI) cut-points for defining the prevalence of
      overweight and obesity in children. These are given in both 6- and 12-month age
      intervals. Since the BMI-for-age curves are nonlinear, a degree of bias will be
      introduced when age intervals are wide. We aimed to quantify this bias in
      prevalence estimates in 2178 Australian children aged 4-12 years using 12- versus
      6-month age intervals. Using the 12-month interval, the prevalence of overweight
      and obesity was underestimated by 1.4% compared to the 6-month interval
      estimates; however, this was age-dependent. It overestimated prevalence for 4
      year olds, but underestimated it for older ages by up to 2.6%. Overweight
      prevalence was generally affected more than obesity prevalence. The use of
      different age intervals for IOTF cut-points introduces a small but systematic
      bias in prevalence estimates of overweight and obesity.

PMID- 16570091
TI  - Early determinants of overweight at 4.5 years in a population-based longitudinal
      study.
AB  - OBJECTIVES: The roots of the obesity epidemic need to be traced back as early in
      life as possible in order to develop effective means for preventing obesity and
      its health consequences in the future. The aim of this paper is to examine a
      broad range of factors that may simultaneously contribute to childhood overweight
      in a population-based cohort of children followed from birth to 4.5 years, to
      determine which factors exert the most influence in early life. DESIGN: The
      analyses were performed using data from the Quebec Longitudinal Study of Child
      Development 1998-2002 (QLSCD). SUBJECTS: The study follows a representative
      sample (n=2103) of children born in 1998 in the Canadian province of Quebec.
      MEASURE: Measured height and weight were available for 1550 children aged 4.5
      years. At 4.5 years, BMI was analyzed using the US CDC sex- and age-specific
      growth charts. In order to study children at their highest weights at various
      ages, odds ratios were presented for high birth weight, weight-for-stature at or
      above the 95th percentile at 5 months, and BMI at or above the 95th percentile at
      4.5 years. Monthly weight gain between birth and five months has been analyzed.
      Children were also evaluated by the Z-score obtained from the standardized weight
      divided by height. Factors potentially related to children's weight include sex,
      gestational age and birth rank, breastfeeding, mothers' smoking status during
      pregnancy, family type at child's birth, and family income before pregnancy and
      when the children were 5 months and 4.5 years old. Other parental factors such as
      height and overweight/obesity (based on BMI) and other maternal factors (age,
      education, immigrant status) were also part of the analysis. RESULTS: Being in
      the highest quintiles of weight gain between birth and 5 months, as well as
      maternal smoking during pregnancy, almost double the odds of being overweight at
      4.5 years. Parental overweight or obesity also increased the odds of being
      overweight at this age, as well as being raised in middle-income or in poor
      families. A greater proportion of children born to nonsmoking mothers with higher
      weights (more than 4000 g) were overweight at 4.5 years, the percentage being
      greatest for those in the highest weight-gain categories from birth to 5 months.
      The pattern was different for children born to smoking mothers. The greatest
      proportion of 4.5-year-old overweight children was seen for children born in the
      normal weight-range category (3000-4000 g) who were in the highest quintiles of
      weight gain from birth to 5 months, and for children with high birth weights
      (more than 4000 g) who were in the lowest quintiles of birth-to-5-months weight
      gain. Children who were overweight at 4.5 years and who had been born to smoking
      mothers started life with a birth weight around that for the population means,
      but they gained more weight in the first 5 months of life than did the children
      of nonsmoking mothers. CONCLUSION: This study indicates that behavioral and
      social factors exert critical influences on the onset of childhood overweight in
      preschool years. From a population-health perspective, interventions aimed at
      preventing childhood obesity would do well to target smoking pregnant women, as
      well as nonsmoking pregnant women at risk for giving birth to high-birth-weight
      children, paying particular attention to rapid weight gain in the first months of
      life.

PMID- 16570092
TI  - Metabolic syndrome in obese Caucasian children: prevalence using WHO-derived
      criteria and association with nontraditional cardiovascular risk factors.
AB  - OBJECTIVE: Studies on the prevalence of metabolic syndrome (MS) in European obese
      children using child-based criteria are scanty. Moreover, it is unknown if
      nontraditional cardiovascular disease (CVD) risk factors are associated with the
      MS at this early age in these subjects. DESIGN AND SUBJECTS: We studied the
      prevalence of the MS in 588 Caucasian obese children and adolescents by devising
      a World Health Organization derived definition and child-specific criteria, whose
      deviation from normalcy was based on an age, sex, and ethnically comparable
      control group of 1363 subjects. In a subgroup of 206 obese children, we
      investigated the association of the MS with nontraditional CVD risk factors.
      MEASUREMENTS: Fasting blood samples for glucose and lipids measurements were
      taken in both control and obese children. In addition, the obese children
      underwent an oral glucose tolerance test. In the subgroup of 206 obese children,
      albumin excretion rate , plasma uric acid, fibrinogen, plasminogen activator
      inhibitor type 1(PAI-1), C-reactive protein, interleukin 6 and white blood cells
      were also measured. RESULTS: The prevalence of MS was 23.3%. A similar prevalence
      of 23% of MS was recorded in the subgroup of 206 obese children in whom
      measurements of nontraditional CVD risk factors were available. After adjustment
      for the degree of obesity, subjects with MS had significantly higher uric acid
      (6.6+/-0.23 vs 6.1+/-0.12 mg/dl, P<0.0001) and PAI-1 plasma concentrations
      (231.4+/-25.50 vs 214.3+/-12.96 ng/ml, P<0.05) and a higher frequency of
      microalbuminuria (37 vs 20%, P<0.05) than those without MS. Microalbuminuria,
      uric acid and PAI-1 explained 10.6% of the variance of MS. CONCLUSION:
      Approximately, a quarter of Caucasian obese children have the MS. The association
      of MS with several nontraditional risk factors for CVD early in life suggests a
      heightened CVD risk in these individuals.

PMID- 16570093
TI  - Depression in adolescent obesity: cultural moderators of the association between
      obesity and depressive symptoms.
AB  - OBJECTIVE: Community studies relating depression to obesity in adolescents have
      generated inconsistent results. It has been argued that the variability in
      findings is due to effect modification by demographic characteristics that vary
      across samples. The aim of this study was to test the hypothesis that the
      strength of the obesity-depression association is moderated by gender, ethnicity
      and socioeconomic status (SES). RESEARCH METHODS AND PROCEDURES: Data were from
      two large, school-based, studies of adolescent health and well-being (n=4320;
      n=1824). Students completed one of two measures of depressive symptoms (SDQ; CES
      D) in school and were weighed and measured. Gender and ethnicity were self
      reported and SES was indexed by residential neighbourhood characteristics or
      individual family deprivation. RESULTS: There was barely any association between
      obesity and depressive symptoms in either sample. There was also no evidence that
      obese participants who were female, white or from higher SES backgrounds were
      especially vulnerable to depressive symptoms. DISCUSSION: The results indicate
      that in community samples of adolescents, regardless of gender, SES or ethnicity,
      reports of depressive symptoms are not significantly higher in obese than normal
      weight groups. The results are discussed in terms of obese adolescents'
      resilience in the face of multiple social adversities.

PMID- 16570094
TI  - Chlorpyrifos exposure in farm families: results from the farm family exposure
      study.
AB  - We used urinary biological monitoring to characterize chlorpyrifos (O,O-diethyl-O
      (3,5,6-trichloro-2-pyridinyl) phosphororthioate) exposure to farm family members
      from Minnesota and South Carolina who participated in the Farm Family Exposure
      Study. Five consecutive 24-h urine samples were obtained from 34 families of
      licensed pesticide applicators 1 day before through 3 days after a chlorpyrifos
      application. Daily 3,5,6-trichloro-2-pyridinol (TCP) urinary concentrations
      characterized exposure profiles of the applicator, the spouse, and children aged
      4-17 years. Self-reported and observed determinants of exposure were compared to
      the maximum postapplication TCP concentration. All participants had detectable (>
      or = 1 microg/l) urinary TCP concentrations at baseline. Applicators' peak TCP
      levels occurred the day after the application (geometric mean (GM) = 19.0
      microg/l). Postapplication TCP change from baseline in the spouses and children
      was negligible, and the only reliable predictor of exposure was assisting with
      the application for children aged 12 years and older. The applicators' exposure
      was primarily influenced by the chemical formulation (GM = 11.3 microg/l for
      granular and 30.9 microg/l for liquid), and the number of loads applied.
      Repairing equipment, observed skin contact, and eating during the application
      were moderately associated TCP levels for those who applied liquid formulations.
      Estimated absorbed doses (microg chlorpyrifos/kg bodyweight) were calculated
      based on TCP excretion summed over the 4 postapplication days and corrected for
      pharmacokinetic recovery. The GM doses were 2.1, 0.7, and 1.0 microg/kg
      bodyweight for applicators, spouses, and children, respectively. Chlorpyrifos
      exposure to farm family members from the observed application was largely
      determined by the extent of contact with the mixing, loading, and application
      process.

PMID- 16570095
TI  - Effects of canopy gaps on the genetic structure of Camellia japonica saplings in
      a Japanese old-growth evergreen forest.
AB  - The genetic structure of Camellia japonica saplings was investigated in relation
      to canopy conditions in an old-growth evergreen forest in Tsushima, Japan. To
      elucidate effects of canopy gaps on genetic structure, a 1 ha study site was
      divided into 20 x 20 m quadrats, which were classified into a gap quadrats (GAP),
      closed canopy quadrats (CLS) and mixed quadrats. Five GAP quadrats and six CLS
      quadrats were analyzed separately. Isolation-by-distance was tested by examining
      the correlation between genetic distance and geographic distance. A significant
      positive correlation was detected for GAP quadrats, whilst that for CLS quadrats
      was significantly smaller and not significantly different from zero. On the other
      hand, an analysis using Moran's I spatial autocorrelation coefficients indicates
      that the genetic structure is weaker in GAP quadrats than in CLS quadrats in
      short distance classes. The values were significantly positive for both types of
      quadrat. These results, along with our field observations on flowering, suggest
      that canopy gaps affect the genetic structure of C. japonica saplings in two
      distinct ways. First, canopy gaps may promote flowering and mating in an
      isolation-by-distance manner within canopy gaps. Second, canopy gaps may promote
      seed production and resulting overlap in seed shadows may weaken fine-scale
      genetic structures.

PMID- 16570098
TI  - The endocannabinoid system and its role in energy homeostasis and abdominal
      obesity management. Proceedings of a meeting, Quebec City, Canada, 20 November
      2004.

PMID- 16570099
TI  - The pharmacology of cannabinoid receptors and their ligands: an overview.
AB  - Mammalian tissues express at least two cannabinoid receptor types, CB1 and CB2,
      both G protein coupled. CB1 receptors are found predominantly at nerve terminals
      where they mediate inhibition of transmitter release. CB2 receptors occur mainly
      on immune cells, one of their roles being to modulate cytokine release.
      Endogenous agonists for cannabinoid receptors also exist, and are all
      eicosanoids. The first-discovered of these 'endocannabinoids' was
      arachidonoylethanolamide and there is convincing evidence that this ligand and
      some of its metabolites can activate vanilloid VRI (TRPV1) receptors. Certain
      cannabinoids also appear to have TRPV1-like and/or non-CB1, non-CB2, non-TRPV1
      targets. Several CB1- and CB2-selective agonists and antagonists have been
      developed. Antagonists include the CB1-selective SR141716A, AM251, AM281 and
      LY320135, and the CB2-selective SR144528 and AM630. These all behave as inverse
      agonists, one indication that CB1 and CB2 receptors can exist in a constitutively
      active state. 'Neutral' cannabinoid receptor antagonists have also been
      developed. CB1 and/or CB2 receptor activation appears to ameliorate inflammatory
      and neuropathic pain and certain multiple sclerosis symptoms. This might be
      exploited clinically by using CB1, CB2 or CB1/CB2 agonists, or inhibitors of the
      membrane transport or catabolism of endocannabinoids that are released in
      increased amounts, at least in animal models of pain and multiple sclerosis. We
      have recently discovered the presence of an allosteric site on the CB1 receptor.
      Consequently, it may also prove possible to enhance 'autoprotective' effects of
      released endocannabinoids with CB1 allosteric enhancers or, indeed, to reduce
      proposed 'autoimpairing' effects of released endocannabinoids such as excessive
      food intake with CB1 allosteric antagonists.

PMID- 16570100
TI  - Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic
      strength.
AB  - The CB1 cannabinoid receptor has attracted much recent interest because of the
      observation that CB1 receptor antagonists have efficacy in treating metabolic
      syndrome and obesity. CB1 receptors also mediate most of the psychotropic effects
      of Delta9-tetrahydrocannabinol (Delta9THC), the principal psychoactive component
      of cannabis. In addition, they are one component of an interesting and widespread
      paracrine signaling system, the endocannabinoid system. The endocannabinoid
      system is comprised of cannabinoid receptors, endogenous cannabinoids, and the
      metabolic pathways responsible for their synthesis and degradation. The details
      of the endocannabinoid system have been most thoroughly studied in the brain.
      Here it has been shown to be intimately involved in several forms of neuronal
      plasticity. That is, activation of CB1 receptors by endocannabinoids produces
      either short- or long-term changes in the efficacy of synaptic transmission. The
      behavioral consequences of these changes are many, but some of the most striking
      and relevant to the current symposium are those associated with endogenous reward
      and consumptive behavior.

PMID- 16570101
TI  - Endocannabinoids, feeding and suckling--from our perspective.
AB  - In this overview we have summarized some aspects of our published work related to
      the effects of the endocannabinoid system on appetite and suckling. As noted also
      by several other groups we have found that anandamide, a major endocannabinoid,
      enhances appetite in mice. On partial or full food deprivation over 24 h the
      levels of 2-arachidonoyl glycerol (2-AG), a second major cannabinoid, are
      initially elevated in mouse brain; however, partial food deprivation over a
      longer period causes reduction of 2-AG levels. Blocking the endocannabinoid
      system with a CB1 antagonist on the 1st day after birth leads to inhibition of
      suckling; later administration also affects suckling, but does not fully block
      it.

PMID- 16570102
TI  - The unfolding cannabinoid story on energy homeostasis: central or peripheral site
      of action?
AB  - Presentations in this symposium addressed effects and modes of action of
      endocannabinoids in various tissues in relation to metabolic disorders.
      Endocannabinoids are produced and exert their effect in various brain sites,
      including the mesolimbic reward circuitry and the hypothalamus. Both of these
      regions have direct ties to energy metabolism regulation, particularly food
      intake and energy expenditure. These data clearly suggest that the observed
      beneficial effects of CB1 (cannabinoid receptor 1) receptor antagonists on
      obesity may be related to the central endocannabinoid system. On the other hand,
      data presented on cannabinoid action in the liver and white adipose tissues
      clearly indicate that CB1-mediated events in affecting metabolic phenotype may
      occur in peripheral tissues as well. This together with the reported results from
      human trials on CB1 antagonists showing that the initial anorectic effect of
      rimonabant is diminished after the first weeks while longer lasting weight loss
      is achieved do indicate that peripheral action of cannabinoids are very important
      in body weight regulation. Should this hold true in the long run, antagonizing
      CB1 receptors with compound not crossing the blood-brain barrier could
      revolutionize pharmaceutical approaches to obesity by offering a tool that short
      cuts the central nervous system.

PMID- 16570103
TI  - The role of the endocannabinoid system in the control of energy homeostasis.
AB  - The endocannabinoid system has recently emerged as an important regulator of
      energy homeostasis, involved in the control of both appetite and peripheral fat
      metabolism. We briefly review current understanding of the possible sites of
      action and cellular mechanisms involved in the central appetitive and peripheral
      metabolic effects of endocannabinoids. Studies in our laboratory, using leptin
      deficient obese rodents and CB1 cannabinoid receptor (CB1)-deficient mice, have
      indicated that endocannabinoids acting via CB1 are involved in the hunger-induced
      increase in food intake and are negatively regulated by leptin in brain areas
      involved in appetite control, including the hypothalamus, limbic forebrain and
      amygdala. CB1-/- mice are lean and are resistant to diet-induced obesity (DIO)
      despite similar energy intake to wild-type mice with DIO, suggesting that CB1
      regulation of body weight involves additional peripheral targets. Such targets
      appear to include both adipose tissue and the liver. CB1 expressed in adipocytes
      has been implicated in the control of adiponectin secretion and lipoprotein
      lipase activity. Recent findings indicate that both endocannabinoids and CB1 are
      present in the liver and are upregulated in DIO. CB1 stimulation increases de
      novo hepatic lipogenesis through activation of the fatty acid biosynthetic
      pathway. Components of this pathway are also expressed in the hypothalamus where
      they have been implicated in the regulation of appetite. The fatty acid
      biosynthetic pathway may thus represent a common molecular target for the central
      appetitive and peripheral metabolic effects of endocannabinoids.

PMID- 16570105
TI  - Endocannabinoids: biology, mechanism of action and functions.

PMID- 16570104
TI  - How many sites of action for endocannabinoids to control energy metabolism?
AB  - The promising results obtained by clinical trials using Rimonabant to tackle
      visceral obesity and related disorders recently promoted a remarkable impulse to
      carry out detailed investigations into the mechanisms of action of
      endocannabinoids in regulating food intake and energy metabolism. The
      endocannabinoid system has been known for many years to play an important role in
      the modulation of the neuronal pathways mediating the rewarding properties of
      food. However, in the last few years, with the advanced understanding of the
      crucial role of the hypothalamic neuronal network in the regulation of appetite,
      several studies have also directed attention to the orexigenic role of the
      endocannabinoid system, substantiating the well known appetite stimulating
      properties of derivatives of Cannabis sativa. Furthermore, the last 2 years have
      seen a number of relevant publications emphasizing the role of endocannabinoids
      as significant players in various peripheral metabolic processes. To date, the
      roles of the endocannabinoid system in influencing energy metabolism have proved
      to be more complex than was formerly believed. However, the diverse ability to
      modulate both central and peripheral processes highlights the pivotal involvement
      of the endocannabinoid system in the control of metabolic processes. This review
      describes the roles of endocannabinoids and the cannabinoid type 1 receptor (CB1)
      in the control of energy balance.

PMID- 16570106
TI  - Contribution of CB1 blockade to the management of high-risk abdominal obesity.
AB  - The worldwide increase in the prevalence of type 2 diabetes represents a
      tremendous challenge for our healthcare system, especially if we consider that
      this phenomenon is largely explained by the epidemic of obesity. However, despite
      the well-recognized increased morbidity and mortality associated with an elevated
      body weight, there is now more and more evidence highlighting that abdominal
      adipose tissue is the fat depot that conveys the greatest risk of metabolic
      complications. This cluster of metabolic abnormalities has been referred to as
      the metabolic syndrome and this condition is largely the consequence of abdominal
      obesity, especially when accompanied by a high accumulation of visceral adipose
      tissue. This cluster of metabolic complications has also been found to be
      predictive of a substantially increased risk of coronary heart disease beyond the
      presence of traditional risk factors. Moreover, a moderate weight loss in
      initially abdominally obese patients is associated with a selective mobilization
      of visceral adipose tissue, leading to improvements in the metabolic risk profile
      predictive of a reduced risk of coronary heart disease and of type 2 diabetes.
      The recent discovery of the endocannabinoid-CB1 receptor system and of its impact
      on the regulation of energy metabolism represents a significant advance, which
      will help physicians target abdominal obesity and its related metabolic
      complications. In this regard, studies have shown that rimonabant therapy (the
      first developed CB1 blocker) could be useful for the management of clustering
      cardiovascular disease risk factors in high-risk abdominally obese patients
      through its effects not only on energy balance but also on adipose tissue
      metabolism. For instance, the presence of CB1 receptors in adipose tissue and the
      recently reported effect of rimonabant on adiponectin production by adipose cells
      may represent a key factor responsible for the weight loss-independent effect of
      this CB1 blocker on cardiometabolic risk variables.

PMID- 16570107
TI  - Endogenous cannabinoids in the brain and peripheral tissues: regulation of their
      levels and control of food intake.
AB  - Endocannabinoids were first defined in 1995 as 'endogenous substances capable of
      binding to and functionally activating the cannabinoid receptors'. To date, two
      well-established endocannabinoids, N-arachidonoylethanolamine (anandamide) and 2
      arachidonoylglycerol (2-AG), as well as a few other putative ligands, all derived
      from long-chain polyunsaturated fatty acids, have been identified in animal
      tissues. The biosynthetic and metabolic pathways for anandamide and 2-AG have
      been elucidated, and most of the enzymes therein involved have been cloned. We
      now know that CB1 receptors, and endocannabinoids in tissue concentrations
      sufficient to activate them, are more widely distributed than originally thought,
      and are found in brain and peripheral organs involved in the control of energy
      intake and processing, including the hypothalamus, nucleus accumbens, brainstem,
      vagus nerve, gastrointestinal tract, adipose tissue and liver. Endocannabinoid
      biosynthetic and inactivating pathways are under the regulation of neuropeptides
      and hormones involved in energy homeostasis, and endocannabinoid levels are
      directly affected by the diet. Endocannabinoids, in turn, regulate the expression
      and action of mediators involved in nutrient intake and processing. These cross
      talks are at the basis of the proposed role of endocannabinoid signalling in the
      control of food intake, from invertebrates to lower vertebrates and mammals, and
      their perturbation appears to contribute to the development of eating disorders.

PMID- 16570109
TI  - Molecular Psychiatry: the highest Immediacy Index in the field of psychiatry.

PMID- 16570110
TI  - Review of range of arytenoid cartilage motion.
AB  - Vocal fold abduction/adduction posturing is key to phonation control. As
      biomechanical models of the larynx increase in complexity, there is a need to
      verify them with laboratory data. To help experimental cross-validation of
      models, ranges of vocal process displacement were reviewed and combined. Although
      general inter-study agreement was found, there was substantial variation. Using a
      model of vocal fold posturing, insights were uncovered that could not otherwise
      be made; best-practice guidelines and research avenues for future studies of
      vocal posturing were also outlined.

PMID- 16570111
TI  - FBP Algorithms for Attenuated Fan-Beam Projections.
AB  - A filtered backprojection (FBP) reconstruction algorithm for attenuated fan-beam
      projections has been derived based on Novikov's inversion formula. The derivation
      uses a common transformation between parallel-beam and fan-beam coordinates. The
      filtering is shift-invariant. Numerical evaluation of the FBP algorithm is
      presented as well. As a special application, we also present a shift-invariant
      FBP algorithm for fan-beam SPECT reconstruction with uniform attenuation
      compensation. Several other fan-beam reconstruction algorithms are also
      discussed. In the attenuation-free case, our algorithm reduces to the
      conventional fan-beam FBP reconstruction algorithm.

PMID- 16570112
TI  - Differential effects of propofol and ethanol on P2X4 receptors expressed in
      Xenopus oocytes.
AB  - The current study investigated the effects of propofol on P2X4 receptors
      expressed in Xenopus oocytes using two-electrode voltage clamp. We also tested
      the effects of 100 mM ethanol on the same oocytes used to test propofol. Propofol
      potentiated ATP-gated currents in a concentration dependent manner in P2X4
      receptors. In agreement with our previous findings, ethanol inhibited P2X4
      receptors. The opposite effects of propofol and ethanol on P2X4 receptor function
      suggest that these anesthetics act via different sites/mechanisms in P2X
      receptors as has been suggested for GABA(A) and glycine receptors.

PMID- 16570113
TI  - Frameless stereotactic subcaudate tractotomy for intractable obsessive-compulsive
      disorder.
AB  - Obsessive-compulsive disorder (OCD) is a chronic, disabling disorder.
      Psychosurgery may be indicated for a subset of patients for whom no conventional
      treatment is satisfactory. This paper focuses on the stereotactic subcaudate
      tractotomy (SST). Thus far, these procedures have been carried out using frame
      based stereotactic techniques. However, modern - highly accurate - frameless
      stereotactic procedures have successfully been introduced in neurosurgical
      practice. We developed a novel frameless stereotactic subcaudate tractotomy
      procedure with promising initial results in a patient suffering from intractable
      OCD. This is the first report on frameless SST. Future studies should examine
      whether other ablative stereotactic psychosurgery procedures can be done using
      frameless stereotactic methods.

PMID- 16570114
TI  - Intracranial non-Hodgkin's MALT lymphoma mimicking a large convexity meningioma.
AB  - Primary presentation of an intradural Non-Hodgkin's lymphoma is rare. Recently
      these B cell lymphomas of mucosa associated lymphoid tissue (MALT) have gained
      acceptance as an important pathological subtype and are distinguishable from
      other primary CNS lymphomas that exhibit aggressive behaviour. Over the past
      decade a number of these lesions have been reported to resemble a meningioma both
      intra-operatively and radiologically. The authors outline such a case of marginal
      zone B cell lymphoma that clinically and radiologically resembled a meningioma.
      This case illustrates the rare occurrence of low grade dural B cell lymphoma and
      the need to consider this entity in the differential diagnosis of CNS lesions, if
      appropriate targeted therapy is to be administered.

PMID- 16570115
TI  - Community mental health in the People's Republic of China: a critical analysis.
AB  - Community mental health has long been the crucial modality in service delivery of
      mental health services. This paper is an attempt to evaluate community mental
      health services in the People's Republic of China. The writer critically argues
      that community mental health services in the People's Republic of China still
      have faced a lot of difficulties such as huge demand but scarce resources,
      withdrawal of governmental funding in related services, inaccessibility of
      services to deprived and remote rural areas, political control, high mental
      health illiteracy and problems in formation of multidisciplinary team. An
      articulation of community mental health in the China context is also discussed.

PMID- 16570116
TI  - Cancer Familial Aggregation (CFA) and G446A polymorphism in ARLTS1 gene.
AB  - ARLTS1--a member of ADP-ribosylation factor family, is a newly described
      candidate tumour suppressor gene. Recent studies show that a nonsense
      polymorphism, G446A (Trp149Stop), in ARLTS1 gene is significantly more frequent
      in familial cancer cases than in sporadic cancer cases. This study presents
      analysis of the germ-line G446A polymorphism in the ARLTS1 gene among 1686
      consecutively collected patients with breast cancer, prostate cancer, malignant
      melanoma, thyroid papillary cancer or laryngeal cancer in Poland. The G446A
      allele was present in 1.81% (9/497) breast cancer patients, 1.46% (5/343)
      prostate cancer patients, 1.76% (7/397) melanoma patients, 1.65% (3/182) thyroid
      papillary carcinoma patients and 2.68% (8/299) of laryngeal cancer patients. The
      frequency of this polymorphism in the control group was 1.45% (8/552).
      Differences in the frequency of the G446A polymorphism between case and control
      groups were not statistically significant. In addition, there was no significant
      difference in the number of Cancer Familial Aggregations (CFA) among breast,
      prostate, thyroid or laryngeal cancer cases harbouring the G446A polymorphism,
      when compared to the G446A negative cases. Interestingly out of the CFA melanoma
      cases, 4/6 (66.6%) were found to harbour the change compared to only 20.2%
      (69/341) sporadic melanoma cases. This difference was statistically significant
      (p = 0.02, OR = 7.8). The results of this study suggest that the G446A in ARLTS1
      gene is probably not associated with an increased risk of sporadic breast cancer,
      prostate cancer, melanoma, thyroid papillary cancer or laryngeal cancer.
      Moreover, the G446A polymorphism is not significantly more frequent in CFA cases
      except for families in which the proband had melanoma. To confirm this result
      more cases of melanoma should be analysed.

PMID- 16570117
TI  - Positive predictive value of breast fine needle aspiration cytology (FNAC) in
      combination with clinical and imaging findings: a series of 2334 subjects with
      abnormal cytology.
AB  - We calculate the positive predictive value (PPV) of abnormal (C3-5) FNAC, alone
      and in combination with clinical and imaging findings, based on a consecutive
      series of 2,334 subjects. The PPV of a C3, C4 or C5 report is 55.0%, 95.9% and
      99.4%, respectively. C5 Cytology is highly predictive of malignancy (PPV=99.4
      99.7%) except where imaging is negative or benign. When C4 cytology is associated
      with suspicious findings on imaging and/or palpation, its PPV increases to 98.5
      98.7%. C3 is the least predictive of malignancy and even when associated with
      suspicious findings on imaging and/or palpation its PPV is 83.3% - C3 FNAC should
      therefore prompt pre-operative core biopsy. These data indicate that FNAB is
      still a useful test in breast diagnosis, and it may assist clinical decision
      making as far as whether patients should progress to surgical management or
      should have further core biopsy before planning surgery.

PMID- 16570119
TI  - Outcomes of a disease-management program for patients with recent osteoporotic
      fracture.
AB  - INTRODUCTION: The purpose of this study was to evaluate outcomes of a disease
      management program designed to increase rates of bone-mineral-density (BMD)
      testing and initiation of osteoporosis medication among patients with a recent
      osteoporotic fracture. STUDY DESIGN: We identified 744 consecutive patients
      aged>or=55 years who were seen at either of 2 of 14 Kaiser Permanente medical
      facilities in Northern California (KPNC) after sustaining a fracture of the hip,
      spine, wrist, or humerus between April 2003 and May 2004. These patients were
      invited to participate in a study of the Fragile Fracture Management Program,
      whose protocol used fracture-risk assessment tools to determine treatment
      recommendations. Postfracture care of study participants was compared with usual
      postfracture care received by osteoporotic-fracture patients at 12 other KPNC
      facilities. RESULTS: Of the 744 patients who were invited to participate in the
      study, 293 (39%) agreed to participate, and 169 (23%) completed the evaluation.
      Of these 169 patients (127 women, 42 men), 65 (51%) of the women and 7 (17%) of
      the men qualified for drug treatment; of these 72 patients, 6 (86%) of the men
      and 41 (63%) of the women accepted the offered treatment. At the two study
      locations, rates of care (BMD testing or prescribing osteoporosis medication)
      were about twice as high as rates of usual postfracture care observed at 12 other
      medical centers in KPNC. CONCLUSIONS: Compared with patients who received usual
      care for osteoporotic fracture, patients participating in a postfracture disease
      management program had substantially higher rates of medical attention given for
      osteoporosis; however, the overall yield of the program was low. This low uptake
      rate was related to factors not previously appreciated: many patients refused
      participation in the program; a high proportion of younger women-and men of all
      ages-did not qualify for treatment; and treatment was refused by one in three
      study-qualified women and by one in seven study-qualified men. Additional efforts
      are needed to overcome patient barriers to improved osteoporosis evaluation,
      treatment and participation in postfracture programs.

PMID- 16570118
TI  - The cost-effectiveness of risedronate in the treatment of osteoporosis: an
      international perspective.
AB  - INTRODUCTION: Risedronate, a bisphosphonate for treatment and prevention of
      osteoporosis, has been shown in several clinical trials to reduce the risk of
      fractures in postmenopausal women with osteoporosis. The cost-effectiveness of
      risedronate treatment has previously been evaluated within different country
      settings using different model and analysis approaches. The objective of this
      study was to assess the cost-effectiveness of risedronate in postmenopausal women
      in four European countries -- Sweden, Finland, Spain, and Belgium -- by making
      use of the same modelling framework and analysis setup. METHODS: A previously
      developed Markov cohort model for the evaluation of osteoporosis treatments was
      used to estimate the cost-effectiveness of risedronate treatment. For each
      country, the model was populated with local mortality, fracture incidence, and
      cost data. Hip fractures, clinical vertebral fractures, and wrist fractures were
      included in the model. RESULTS: The incremental cost per quality-adjusted life
      years (QALY) gained from a 5-year intervention with risedronate compared to "no
      intervention" in 70-year-old women at the threshold of osteoporosis [T-score = 
      2.5 based on National Health and Nutrition Examination Survey (NHANES) III data]
      and previous vertebral fracture was estimated to be euro 860, euro 19,532, euro
      11,782, and euro 32,515 in Sweden, Finland, Belgium, and Spain, respectively.
      Among 70-year-old women at the threshold of osteoporosis without previous
      fracture the estimated cost per QALY gained ranged from euro 21,148 (Sweden) to
      euro 80,100 (Spain). The differences in cost-effectiveness between countries are
      mainly explained by different costs (fracture and treatment costs), fracture
      risks, and discount rates. Based on cost per QALY gained threshold values found
      in the literature, the study results indicated risedronate to be cost effective
      in the treatment of elderly women with established osteoporosis in all the
      included countries. CONCLUSIONS: At a hypothetical threshold value of euro 40,000
      per QALY gained, the results in this study indicate that risedronate is a cost
      effective treatment in elderly women at the threshold of osteoporosis (i.e., a T
      score of -2.5) with prevalent vertebral fractures in Sweden, Finland, Belgium,
      and Spain.

PMID- 16570120
TI  - Photoradiation could influence the cytoskeleton organization and inhibit the
      survival of human hepatoma cells in vitro.
AB  - Low-power laser therapy has become popular in clinical applications including
      promoting wound healing and pain relief. However, effects of this photoradiation
      on human hepatoma cells are rarely studied. Previously, we found 808 nm gallium
      aluminum arsenide (GaAlAs) continuous wave laser had an inhibitory effect on the
      proliferation of human hepatoma cell lines HepG2 and J-5 at the energy density of
      5.85 and 11.7 J/cm(2), respectively. The aim of the present study was to evaluate
      the possible mechanism of action of this photoradiation on HepG2 and J-5 cells.
      HepG2 and J-5 cells were cultured in 24-well plates for 24 h. After
      photoradiation by 130 mW 808 nm GaAlAs continuous wave laser for different time
      intervals (0, 30, 60, 90, 120, 150, and 180 s), Western blot and
      immunofluorescent staining were used to examine the expression and distribution
      of histone and cytoskeletal proteins. The cell counts as well as histone and
      synemin expression of HepG2 and J-5 cells were reduced by photoradiation at the
      energy density of 5.85 and 11.7 J/cm(2), respectively. Furthermore, the
      architecture of cytoskeletons and the distribution of intermediate filament
      associated proteins (plectin and synemin) were disorganized by photoradiation.
      Photoradiation by 808 nm GaAlAs continuous wave laser at the energy density of
      5.85 and 7.8 J/cm(2) inhibited the survival of human hepatoma cell lines. The
      mechanism might reduce synthesis of histone and synemin. Reduced histone
      synthesis might further reduce the proliferation rate of these cells. Reduced
      synemin synthesis might result in the destruction of the cytoskeleton. Therefore,
      the net effects by this photoradiation were reduced cell survival.

PMID- 16570121
TI  - Transcriptome profiling of lung schistosomula,in vitro cultured schistosomula and
      adult Schistosoma japonicum.
AB  - The schistosomulum is the main target of vaccine-induced protective immunity;
      however, most studies have utilized schistosomula produced by mechanical
      transformation of infective larvae followed by in vitro culture rather than
      larvae isolated directly from the lungs of infected mammals. Using transmission
      electron microscopy, we demonstrated that there was little difference in the
      ultrastructure of Schistosoma japonicum schistosomula obtained by the two
      methods. However, significant differences in gene expression profiles were
      apparent when we used an oligonucleotide microarray to compare the gene
      expression profiles of schistosomula obtained in vivo from lung tissue with those
      maintained in vitro, and with adult worms of S. japonicum. It is likely that host
      environmental factors, which cannot be reliably reproduced in vitro, do influence
      the growth, development and overall biology of schistosomes. Thus caution is
      urged when using in vitro-cultured schistosomes and mechanically
      transformed/cultured schistosomula in molecular, biochemical and immunological
      studies.

PMID- 16570123
TI  - Apoptotic cell death in the central nervous system of Bufo arenarum tadpoles
      induced by cypermethrin.
AB  - Tadpoles of the toad Bufo arenarum treated with cypermethrin (CY) at
      concentrations above 39 mug CY/L showed dose-dependent apoptotic cell death in
      immature cells of the central nervous system as demonstrated by morphometric
      analysis, the TUNEL method, and DNA fragmentation assay. Light-and electron
      microscopic studies showed structural alterations in the intermediate and
      marginal layers of the brain. Immature cerebral tissue showed cellular shrinkage,
      nuclear fragmentation and increase of intercellular spaces. In this study we
      demonstrated high toxicity of CY to larval stages of Bufo arenarum. Our results
      show that doses lower than those used in routine insecticide applications can
      cause massive apoptosis in the immature cells of the central nervous system.
      These results coincide with our previous studies in Physalaemus biligonigerus,
      confirming the severe toxic effects of CY to the central nervous system of anuran
      species from Argentina. This may increase the mortality index in wild animals and
      contribute to the loss of biodiversity in our agroecosystems. We postulate that
      CY induces apoptosis in central nervous system cells of Bufo arenarum tadpoles by
      specific neurotoxic mechanisms.

PMID- 16570122
TI  - Differential expression of ABH histo-blood group antigens and LAMPs in infantile
      hemangioma.
AB  - Although infantile hemangioma (IH) are the most common tumors of infancy, the
      mechanism of their proliferation and involution remains vague. Proliferation,
      differentiation and death of endothelial cells are the basic processes involved
      in their pathobiology. Here we hypothesize that the glycoconjugates ABH histo
      blood group antigens (HBGA) and lysosome-associated membrane proteins (LAMPs)
      might be implied in both the differentiation and death of endothelial cells
      during vascular remodeling in IH. Proliferating and involuting IH were examined
      immunohistochemically for HGBA and LAMP expression together with vWF and CD31.
      Proliferative and apoptotic indices were determined. LAMPs were found in immature
      endothelium of proliferating IH. In involution an increased number of
      immunopositive cells stained with higher intensity was detected. The enhanced
      expression might be associated with augmented autophagy required for tissue
      remodeling during tumor involution. HBGA presented an opposite pattern of
      expression--they stained intensely the endothelium of mature capillaries, while
      the immature ones were positive for vWF. The presence of HBGA in endothelial
      cells of IH may be related to the differentiation process only, as well as to
      endothelial adhesion and angiogenesis. Novel evidence for differential expression
      of HBGA and LAMPs in proliferative and involutive phases of IH is presented.

PMID- 16570124
TI  - Morphological plasticity of Primula nutans to hummock-and-hollow microsites in an
      alpine wetland.
AB  - Hummock-and-hollow microtopography is common in wetlands of the Qinghai-Tibetan
      Plateau. The physical environment of hummocks contrasts strongly with that of
      hollows. To address how Primula nutans Georgi, a herbaceous species broadly
      distributed on the plateau, can inhabit both hummocks and hollows, we
      investigated the plasticity of its morphology and biomass growth in relation to
      the environmental variables during the growing season. The results are as
      follows: (1) total daily photosynthetic photon flux density, maximum soil
      temperature, and diurnal soil temperature range were significantly larger on the
      hummocks than in the hollows; (2) individual ramets had smaller leaves, higher
      leaf mass per unit area, and shorter petiole and peduncle length on the hummocks,
      but leaf and root dry weights per ramet differed little between microsites; (3)
      P. nutans allocated most of its dry mass to peduncles and flowers and the
      proportion of reproductive mass was significantly higher for plants in the
      hollows than on the hummocks; (4) the coefficients of variation of most
      morphological and biometric parameters was higher on hummocks than in hollows.
      The results suggest that P. nutans favors hummocks but can tolerate hollows
      through morphological adjustments in that the mass investment to peduncles and
      flowers is much larger in plants in the hollows than hummocks.

PMID- 16570125
TI  - Identification and characterization of a novel heat shock transcription factor
      gene, GmHsfA1, in soybeans (Glycine max).
AB  - Plants have a large family of HSFs with different roles in the heat shock
      response that mediate the expression of HSP regulated genes. The HSF encoding
      genes are easily identified by their highly conserved modular structure and
      motifs. In the present study, a putative GmHsfA1 was identified and characterized
      from the soybean expressed sequence tag (EST) database by sequence comparison
      with the functionally well-characterized LpHsfA1 and rapid amplification of cDNA
      ends (RACE). Multiple alignment showed that the amino acid sequence of GmHSFA1,
      matching best with LpHSFA1 (52.2% similarity), was obviously different from that
      of each of several HSFA1s from other plant species. The GmHsfA1 has a
      constitutive expression profile in the different tissues examined. The
      overexpression of GmHsfA1 in transgenic soybean plants led to the activation of
      GmHsp70 under normal temperature and the overexpression of GmHsp70 under high
      temperature. Furthermore, transgenic soybean plants with GmHsfA1 overexpression
      showed obvious enhancement of thermotolerance under heat stress in comparison
      with non-transgenic plants. The experimental results suggested that GmHSFA1 is a
      novel and functional heat-shock transcription factor.

PMID- 16570126
TI  - Diversity of secondary endosymbiont-derived actin-coding genes in cryptomonads
      and their evolutionary implications.
AB  - In the secondary endosymbiotic organisms of cryptomonads, the symbiont actin
      genes have been found together with the host one. To examine whether they are
      commonly conserved and where they are encoded, host and symbiont actin genes from
      Pyrenomonas helgolandii were isolated, and their specific and homologous regions
      were digoxigenin (DIG) labeled separately. Using these probes, Southern
      hybridization was performed on 13 species of cryptomonads. They were divided into
      three groups: (1) both host and symbiont actin gene signals were detected, (2)
      only the host actin gene signal was detected, and (3) host and unknown actin
      signals were detected. The phylogenetic analysis of these actin gene sequences
      indicated that the evolutionary rates of the symbiont actin genes were
      accelerated more than those of the hosts. The unknown actin signals were
      recognized as the highly diverged symbiont actin genes. One of the diverged
      symbiont actin sequences from Guillardia theta is presumed to be as a pseudogene
      or to its precursor. Southern hybridizations based on the samples divided by
      pulsed-field gel electrophoresis showed that all actin genes were encoded by the
      host nuclei. These results possibly represent the evolutionary fate of the
      symbiont actin gene in cryptomonads, which was firstly transferred from the
      symbiont nucleus or nucleomorph, to the host nucleus and became a pseudogene and
      then finally disappeared there.

PMID- 16570128
TI  - Coping strategies and social support in old age psychosis.
AB  - BACKGROUND: According to vulnerability-stress models of psychosis, cognitive and
      behavioural coping strategies can help mediate the potentially negative effects
      of daily stressors. The nature, frequency and effectiveness of coping have been
      studied in people with psychosis under 65 years of age. However, these findings
      may not generalise to older people with the diagnosis, as the nature of stressors
      and coping strategies may change with increasing age. This study therefore aimed
      to explore coping in older patients with psychosis. METHODS: A total of 48 older
      patients with psychosis (F20-29, ICD-10) and 25 non-clinical elderly controls
      were compared using self-report measures of stressors, perceived control over
      stressors, coping strategies, perceived coping efficacy and social support. A
      regression analysis was used to explore predictors of dysfunctional coping in the
      patient group. RESULTS: Patients used a significantly higher proportion of
      problem-focused coping strategies, but they were more dysfunctional copers and
      rated their coping as less effective compared to controls. They also had fewer
      friends and less emotional support. Severity of symptoms was a significant
      predictor of dysfunctional coping when depression, cognitive impairment and
      functional disability were controlled. CONCLUSIONS: Patients with psychosis coped
      less well with daily stressors than controls and patients with more severe
      symptoms were more dysfunctional copers. The findings highlight the potential
      benefit of psychosocial interventions in old age psychosis.

PMID- 16570127
TI  - Cytoskeletal organization during xylem cell differentiation.
AB  - The water and mineral conductive tube, the xylem vessel and tracheid, is a highly
      conspicuous tissue due to its elaborately patterned secondary-wall deposition.
      One constituent of the xylem vessel and tracheid, the tracheary element, is an
      empty dead cell that develops secondary walls in the elaborate patterns. The wall
      pattern is appropriately regulated according to the developmental stage of the
      plant. The cytoskeleton is an essential component of this regulation. In fact,
      the cortical microtubule is well known to participate in patterned secondary cell
      wall formation. The dynamic rearrangement of the microtubules and actin filaments
      have also been recognized in the cultured cells differentiating into tracheary
      elements in vitro. There has recently been considerable progress in our
      understanding of the dynamics and regulation of cortical microtubules, and
      several plant microtubule associated proteins have been identified and
      characterized. The microtubules have been observed during tracheary element
      differentiation in living Arabidopsis thaliana cells. Based on this recently
      acquired information on the plant cytoskeleton and tracheary element
      differentiation, this review discusses the role of the cytoskeleton in secondary
      cell wall formation.

PMID- 16570129
TI  - Explaining service use for mental health problems in the Dutch general
      population: the role of resources, emotional disorder and functional impairment.
AB  - OBJECTIVE: To analyse explanations of service use in terms of resources,
      emotional (mood or anxiety) disorder and functional impairment. METHOD: Data was
      derived from a prospective cohort study in a sample representative (n = 4848) of
      the Dutch adult general population. RESULTS: The occurrence of an emotional (mood
      or anxiety) disorder led to a greater use of services as a partial consequence of
      the functional impairments that accompanied the disorder, but this applied only
      to primary care services and not to specialised mental health services. After
      adjustment for the influence of all other determinants in the model, people with
      more education and those with higher neuroticism scores were more likely to use
      specialised services in particular. CONCLUSIONS: Future research could benefit
      from applying the models derived here to further clarify the use of the two
      service modalities, as well as to assess additional psychological resources.

PMID- 16570130
TI  - Influence of examiner differences on KIG-classification when assessing
      malocclusions.
AB  - OBJECTIVE: Indication systems such as the German KIG system (Kieferorthopadische
      Indikationsgruppen = Orthodontic Indication Groups) presuppose the objective
      assessment of underlying malocclusions. In this survey, we aimed to investigate
      the degree of agreement among the findings of several examiners in the assessment
      of different malocclusions and their classification according to the KIG system.
      SUBJECTS AND METHODS: Calibrated examiners assessed in the clinical evaluation
      and on plaster models orthodontic malocclusions in 180 adults (aged 20-49, 64
      male, 116 female) from the population-based Study of Health in Pomerania (SHIP).
      Clinical examination was carried out by an experienced orthodontist, and the
      plaster models were also analysed by an examiner experienced in orthodontics. To
      compare inter- and intra-individual model examiners, we had two examiners with
      differing orthodontic experience carry out additional analyses of 60 of the 180
      models (29 male, 31 female). RESULTS: The examiner differences yielded various
      KIG classifications and hence different assessments (i. e., whether KIG case
      costs should be borne by health insurance). The comparison "clinical examination
      versus model analysis" revealed differences regarding 16.7% of the study
      participants in the assessment of whether the expense would be borne by the
      statutory health insurance fund. At 5.0-8.3%, the number of participants whose
      assessments had differed was much smaller in the inter-individual comparison of
      model-examiners and was smallest (at 3.3-6.7%) when comparison was made between
      intra-individual assessments (by a sole examiner). With regard to overall
      malocclusion assessment, the greatest examiner differences were again revealed
      when comparing the clinical examination with the model analysis (median kappa
      0.57). The model-examiner comparison revealed larger differences among examiners
      with less orthodontic experience (median kappa 0.61 and 0.62) than the comparison
      between examiners with orthodontic experience (median kappa 0.70). CONCLUSIONS:
      There can occasionally be considerable examiner differences in the classification
      of participants according to orthodontic indication groups and hence varying
      assessments of whether such persons are KIG cases or not. Various means of data
      collection (clinical evaluation-plaster models) in the assessment of
      malocclusions by multiple examiners and by those with little orthodontic
      experience may negatively influence agreement among examiners.

PMID- 16570131
TI  - Proportional growth of craniofacial regions.
AB  - OBJECTIVE: The ratio of the cranium to the face has been traditionally reported
      in textbooks without any firm evidence base. The present study was undertaken to
      measure the increase in size with age of the cranium, face, upper and lower face
      components. METHOD: Bolton standard mean outlines for ages 1 to 18 years were
      analysed by the Autoceph computer program. We measured the area of each
      craniofacial component outline. RESULTS: The ratio of the size of the cranium to
      the face was less than previously reported at birth, 2 years, and 5 years of age,
      but more nearly correct in the adult. Growth of the cranium largely ceased by 9
      years indicating precocious growth of the brain in relation to the face. The size
      of the face increased relative to the cranium by 69%. The lower face increased
      relative to the upper face by 22%. The average percentage increase in area was
      78% lower face, 68.9% total face, 58.8% upper face, 26% cranium. The absolute
      growth rate of the face was greater than that of the cranium, and that of the
      lower face was greater than that of the upper face. The 95% confidence intervals
      for the growth rates did not overlap, indicating a statistically significant
      difference. The relative growth rate (cm2/cm2/yr) was 0.0444 lower face, 0.0391
      total face, 0.0328 upper face, 0.0084 cranium. CONCLUSIONS: There was a
      differential gradient of change increasing from the cranium to the upper face to
      the lower face. This gradient was most clearly expressed by the relative growth
      rates and average percentage increases in area.

PMID- 16570132
TI  - Treatment outcome in angle class II, division 1 patients in pre-puberty and
      puberty after jumping-the-bite appliance.
AB  - AIM: The aim of this study was to investigate whether, and if so, to what extent,
      skeletal and dento-alveolar developments of the stomatognathic system take a
      different course due to influence of Trankmann's jumping-the-bite appliance (JTB)
      in pre-pubertal and pubertal patients in comparison to untreated control groups
      presenting the same conditions at baseline. We aim to discover whether the
      results are better when the device is used on prepubertal children, or those in
      puberty. PATIENTS AND METHODS: Two lateral cephalograms were scanned in treated
      children presenting Angle Class II, Division 1 malocclusion; they were scanned in
      untreated children with the same distoclusion at intervals between at least 11
      months and at most 25 months. The same procedure was taken in children in pre
      puberty (female, min. = 8.6 yrs, max. = 11 yrs; male, min. = 9 yrs, max. = 12.6
      yrs) and in puberty (female, min. = 11 yrs, max. = 14 yrs; male, min. = 12.6 yrs,
      max. = 15 yrs). The cephalometric analysis was made with the orthodontics-PC
      program Onyx Ceph (Image Instruments, Chemnitz, Germany) using a modified
      Bergen/Hasund analysis [7, 8]. RESULTS: The Angle Class II, Division 1
      malocclusion of all treated patients evolved into an Angle Class I occlusion via
      Trankmann's JTB design. The location of this transformation was mainly dento
      alveolar in both pre-puberty and puberty. The differences between the control and
      JTB groups concerning the development of cephalometric values in pre-pubertal age
      were unremarkable if one considers the range of reading error. The exception to
      this was with angleUP1-NA, which increased more in the control group than in the
      treated group. angleSNB, arB (mm), angleANB and angleML-NSL showed greater change
      in the targeted direction in the control group than in the JTB group in pubertal
      patients. The increase in the arA length (mm) was clearly, but not statistically
      significantly, inhibited by the JTB in puberty. Comparing both treated groups,
      one can conclude that cephalometric values developed more favorably in the pre
      pubertal than in the pubertal patients, with the exception of angleSNA.

PMID- 16570133
TI  - The derotation of premolars and canines with NiTi elements.
AB  - BACKGROUND: Canines or premolars must often be derotated during fixed appliance
      therapy. If such derotation is carried out on the continuous archwire during the
      leveling phase, it may lead to unwanted side effects on the neighboring teeth.
      MATERIAL AND METHODS: At the University of Ulm a .018" x .018" nickel-titanium
      segmental derotation archwire was developed to start derotation as early as
      possible. This wire can be inserted during leveling. This system consists of a
      vertical slot bracket, an elastic ligature, and the derotation archwire. We
      tested the derotation archwire under clinical application. The occurring forces
      and torquing moments were measured in vitro via a hexapode and a sensor working
      in three dimensions. RESULTS: In this investigation, a derotation moment of 12
      Nmm occurred in the canine with a 140 degrees archwire rotation and a force in
      lingual direction. This archwire also made overcorrection possible, since it
      remains active after complete derotation. A complete derotation of the tooth was
      effected with no reactivation, due to the wire's superelasticity.

PMID- 16570134
TI  - In-vitro investigations on suitability of light-cured resins for interocclusal
      splints: part I: mechanical properties.
AB  - OBJECTIVE: It was the aim of the present study to investigate the material
      properties of different resins and their suitability for the fabrication of
      occlusal and intermaxillary splints. MATERIAL AND METHOD: We subjected auto
      polymerized resins (Palapress, Orthocryl, Steady-Resin M) and light-polymerized
      resins (Acrylight, Primosplint, Triad TranSheet Colorless and Pink) to
      investigation. The Targis Power light oven was used to polymerize the light-cured
      resins. After the auto-polymerized resins had been mixed by hand and filled into
      the forms, they were polymerized for 15 minutes in a high-pressure polymerization
      machine (Palamat) at 2 bar. The parameters examined were flexural strength, water
      adsorption, and polymerization shrinkage. Tests carried out according to DIN EN
      ISO 1567 served to determine flexural strength, flexural modulus, and water
      adsorption. Polymerization shrinkage was determined via the buoyancy test.
      RESULTS: The resins' flexural strength ranged from 60 to 101 MPa. Flexural moduli
      lay between 1.3 and 5.3 GPa. The water adsorption noted in light-cured resins
      amounted to 2.1-4.6 mass percent. Palapress and Steady-Resin displayed the lowest
      water adsorption with 2.0 mass percent. The light-polymerized resins revealed
      significantly less shrinkage (p < 0.05) than the autopolymerized resins tested in
      this study. CONCLUSION: Our results demonstrate that the light-cured resins-with
      the exception of Acrylight -easily match and even exceed the material properties
      of the cold-polymerized resins regarding flexural strength, flexural modulus,
      water adsorption and polymerization shrinkage. The light-cured resins examined
      thus seem suitable for use as splint material.

PMID- 16570135
TI  - In-vitro investigation on suitability of light-cured resins for interocclusal
      splints : part II: surface hardness.
AB  - OBJECTIVE: The aim of the present study was to determine the surface hardness of
      light- and auto-cured resins for the fabrication of occlusal splints employing
      Vickers hardness measurements. MATERIALS AND METHOD: In this study we used three
      auto-polymerized resins (Palapress, Orthocryl, Steady-Resin M) and four light
      polymerized resins (Acrylight, Primosplint, Triad Tran- Sheet Colorless and Triad
      TranSheet Pink). The Vickers hardness measurement was carried out by means of a
      universal Durimet indenter applying a test load of 50 g for 30 seconds. The light
      cured resins were polymerized in a Tagris Power light oven for 10 and 15 minutes
      each. Three separate test series were carried out (the hardness of plates under
      optimal conditions and of occlusal splints was measured, and the curing of light
      polymerizing materials in layers of varying depth was evaluated). Data underwent
      statistical analysis via ANOVA and the Scheffe test. RESULTS: The microhardness
      determined in each case amounted to values between 10.4 HV 0.5 and 39.3 HV 0.5.
      The Vickers hardness determined for the plates that had been produced under
      optimal conditions demonstrated that their surface was significantly (p < 0.05)
      harder than that of cylinders and splints. The hardness values of the light-cured
      material Triad TranSheet Pink (39.3 HV 0.5) were significantly higher (p < 0.05)
      than those of all other resins. In all auto-polymerized resins, the surface
      hardness of the samples we examined (in the form of plates and splints) was
      significantly lower (p < 0.05) than that of the light-cured materials Triad
      TranSheet Pink and Colorless. CONCLUSION: The results we have obtained so far
      concerning surface hardness indicate that, in the fabrication of occlusal
      splints, light-cured resins may represent an alternative to auto-polymerizing
      materials.

PMID- 16570137
TI  - Methicillin-resistant Staphylococcus aureus in community-acquired meningitis.

PMID- 16570136
TI  - Signal transduction underlying the vascular effects of sphingosine 1-phosphate
      and sphingosylphosphorylcholine.
AB  - Two related lysosphingolipids, sphingosine 1-phosphate (S1P) and
      sphingosylphosphorylcholine (SPC) mediate diverse cellular responses through
      signals transduced by either activation of G-protein coupled receptors or
      possibly by acting intracellularly. Vascular responses to S1P and SPC measured
      both in vivo and in dissected vessels show predominantly vasoconstriction with
      some evidence for vasodilation. Although stimulation with S1P or SPC generally
      leads to similar vascular responses, the signalling pathways stimulated to
      produce these responses are often distinct. Nevertheless, mobilization of Ca2+
      from intracellular stores and influx of extracellular Ca2+, which both increase
      [Ca2+]i, occur in response to S1P and SPC. Both mobilization of Ca2+ from
      intracellular stores and influx of extracellular Ca2+ occur in response to S1P
      and SPC. As well, both S1P and SPC induce Ca2+-sensitization in vascular smooth
      muscle which is mediated through Rho kinase activation. In the endothelium, S1P
      and SPC stimulate the production of the vasodilator, nitric oxide through
      activation of endothelial nitric oxide synthase. This activation occurs through
      phosphorylation by Akt and through binding of Ca2+-calmodulin upon increased
      [Ca2+]i. These lysosphingolipids also activate cyclooxygenase-2 which produces
      prostaglandins with both vasoconstrictor and vasodilator properties. A balance
      between the signals inducing vasodilation versus the signals inducing
      vasoconstriction will determine the vascular outcome. Thus, perturbations in S1P
      and SPC concentrations, relative expression of receptors or downstream signalling
      pathways may provide a mechanism for pathophysiological conditions such as
      hypertension. Given this background, recent studies examining a potential role
      for S1P and SPC in hypertension and vascular dysfunction in aging are discussed.

PMID- 16570138
TI  - Identification of novel rainbow trout (Onchorynchus mykiss) chemokines, CXCd1 and
      CXCd2: mRNA expression after Yersinia ruckeri vaccination and challenge.
AB  - Chemokines play important roles in controlling leukocyte trafficking under normal
      and inflammatory conditions. Sixteen CXC chemokines have been identified in the
      human and mouse genomes, while considerably fewer teleost fish CXC chemokines
      have been reported. Here, we describe a novel clade of trout (Onchorynchus
      mykiss) CXC chemokines, designated Onmy CXCd, and we identify a novel gene,
      CXCd1, and a putative duplicate, CXCd2. The trout CXCd proteins contain 112 amino
      acids and the CXCd1 gene is comprised of four exons and three introns.
      Constitutive CXCd mRNA expression was detected in skin, gill, visceral fat, and
      posterior kidney tissues, while low transcript levels were present in the
      anterior kidney and spleen. Spleen CXCd transcript abundance increased 1 day
      after bath vaccination (fourfold) and subsided to basal levels by 7 days
      postvaccination. Challenge with viable Yersinia ruckeri induced expression of
      trout CXCd RNA up to ninefold in the spleen. The number of viable Y. ruckeri were
      significantly correlated with CXCd gene transcript abundance (P = 0.0051,
      Spearman correlation 0.497, n = 30 fish), and fish with the highest bacterial
      loads had the highest CXCd expression. In contrast, pro-inflammatory cytokine IL
      1-beta2 mRNA levels were elevated in fish infected with low numbers of Y.
      ruckeri, while diminishing in heavily infected fish. CXCd mRNA expression was not
      increased in rainbow trout infected with infectious hematopoietic necrosis virus,
      suggesting that up-regulation may be pathogen-specific. Taken together, these
      results indicate that CXCd transcript elevation follows the pro-inflammatory
      cytokine response to Y. ruckeri and may be a relevant immunological marker of
      exposure.

PMID- 16570140
TI  - Theoretical 49Ti NMR chemical shifts.
AB  - 49Ti chemical shifts for a total of 20 titanium complexes are reported, and
      several levels of theory are evaluated in order to identify a reliable approach
      for the calculation of titanium NMR data. The popular B3LYP/6-31G(d)//B3LYP/6
      31G(d) proves to give very good agreement with experimental data over a range
      from 1,400 to -1,300 ppm. The MP2/6-31G(d)//MP2/6-31G(d) level computes even
      smaller average deviations but fails for TiI(4). This behavior together with its
      huge demand for computational resources requires careful handling of this
      theoretical level. In addition, NMR data for five titanium fulvene (or related)
      complexes are given.

PMID- 16570139
TI  - HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype
      structure and variation spanning the nonclassical class I genes.
AB  - Despite several studies that defined the polymorphism of the nonclassical human
      leukocyte antigen-E (HLA-E), HLA-F, and HLA-G genes, most polymorphisms thus far
      examined in correlative studies were derived from the coding sequences of these
      genes. In addition, some discrepancies and ambiguities in the available data have
      persisted in current databases. To expand the data available and to resolve some
      of the discrepant data, we have defined protocols that allow for the
      amplification of 6 to 7 kb of contiguous genomic sequence for each gene,
      including all of the coding and intron sequences, approximately 2 kb of 5'
      flanking promoter sequence, and 1 kb of 3' flanking sequence. Using long-range
      polymerase chain reaction (PCR) protocols, generating either one or two PCR
      products depending on the locus, amplified genomic DNA was directly sequenced to
      completion using a set of about 30 primers over each locus to yield contiguous
      sequence data from both strands. Using this approach, we sequenced 33 genomic
      DNAs, from Asian, African American, and Caucasian samples. The results of this
      analysis confirmed several previously reported coding sequence variants,
      identified several new allelic variants, and also defined extensive variation in
      intron and flanking sequences. It was possible to construct haplotype maps and to
      identify tagging single nucleotide polymorphisms that can be used to detect the
      composite variation spanning all three genes.

PMID- 16570142
TI  - Design of a method for generation of gas-phase hydroxyl radicals, and use of HPLC
      with fluorescence detection to assess the antioxidant capacity of natural
      essential oils.
AB  - The use of natural antioxidants is of increasing importance in the human diet,
      because they are recognised as compounds essential to health which minimize or
      delay the aging process. Despite apparent simplicity, however, it is very
      difficult to measure and quantify such properties, for which a robust analytical
      method is required. Because oxidation usually is caused by the presence of OH*
      radicals, a new method involving the in-situ, vapour-phase generation of these
      radicals and their quantification in the presence and absence of potential
      antioxidant extracts has been developed. The oxidant atmosphere generated from
      hydrogen peroxide is carried by an air stream through an empty quartz chamber in
      which UV radiation promotes the formation of radicals by a photochemical
      reaction. The products then pass through a cartridge containing the essential
      oil, finally bubbling into an impinger containing an aqueous solution of
      salicylic acid, at pH 4.5, which reacts with the OH* radicals forming 2,5
      dihydroxybenzoic acid. This solution is quantified by RP-HPLC using UV and
      fluorescence detectors connected in series. Detection and quantification limits
      for OH* radicals were approximately 0.01 pg g(-1) air. Description and
      optimization of the method are discussed, as also is the antioxidant performance
      of an extract of ginger (Zingiber officinale R.), which reduced the oxidation
      process by up to 92%.

PMID- 16570141
TI  - Comparison of fundamental sonography, tissue-harmonic sonography, fundamental
      compound sonography, and tissue-harmonic compound sonography for focal hepatic
      lesions.
AB  - Image qualities of fundamental, tissue-harmonic, fundamental compound, and tissue
      harmonic compound sonography for evaluating focal hepatic lesions were compared.
      Two radiologists, blinded to the type of techniques and to the final diagnosis,
      independently evaluated 384 images of 96 hepatic lesions: hemangiomas (n=35),
      hepatic cystic lesions (n=28), cirrhosis-related nodules (n=22), focal nodular
      hyperplasia (n=1), and metastases (n=10). All images were graded in terms of
      lesion conspicuity, margin sharpness, and overall image quality using a 4- or 5
      point scale. In the cases of cystic lesions, posterior acoustic enhancement and
      internal artifacts were also analyzed. A Friedman test was used for multiple
      statistical comparisons of the four techniques for all parameters. Compound
      imaging was significantly superior to fundamental imaging regarding lesion
      conspicuity, margin sharpness, and overall quality (P<0.05). For posterior
      enhancement and internal artifacts within the cyst, harmonic ultrasonography (US)
      was significantly better than fundamental US (P<0.05). For evaluating focal
      hepatic lesions on US, compound imaging provided better lesion conspicuity,
      better margin sharpness, and better overall image quality than fundamental
      imaging did. Tissue harmonic imaging also provided better posterior enhancement
      and fewer internal artifacts of the cyst than fundamental imaging.

PMID- 16570143
TI  - Systematic line selection for online coating thickness measurements of galvanised
      sheet steel using LIBS.
AB  - LIBS can be used as an online method of characterizing galvanized coatings on
      sheet steel moving through a production line. The traversing sheet steel is
      irradiated with a series of single laser bursts, each at a different position on
      the sheet steel. An ablation depth in the same range as the coating thickness
      (about 10 microm) is achieved by using a Nd:YAG laser at 1064 nm in collinear
      double-pulse mode. The coating thickness is determined from the ratio of the
      intensities of an iron line and a zinc line measured at a burst energy high
      enough to penetrate the coating with a single burst. Experiments at different
      burst energies were carried out to optimize the thickness resolution, and a
      method of systematically selecting iron and zinc lines was deduced, which is
      based on multivariate data analysis (MVDA) of the intensity ratios calculated for
      a set of 6 zinc lines and 21 iron lines. A temperature correction was applied,
      because the parameters of the plasma change with burst energy, and the influence
      of this on the thickness resolution is discussed. The ambient atmosphere present
      (air, Ar, N2) as well as self-absorption of spectral lines both have an influence
      on the thickness resolution. At optimum conditions, a thickness measurement
      accuracy of better than 150 nm was obtained for a set of electrolytic galvanized
      sheet steels with coating thicknesses in the range 4.1-11.2 microm.

PMID- 16570144
TI  - New approach to online monitoring of the Al depth profile of the hot-dip
      galvanised sheet steel using LIBS.
AB  - In this study a new approach to the online monitoring of the Al depth profile of
      hot-dip galvanised sheet steel is presented, based on laser-induced breakdown
      spectroscopy (LIBS). The coating composition is measured by irradiating the
      traversing sheet steel with a series of single laser bursts, each at a different
      sheet steel position. An ablation depth in the same range as the coating
      thickness (about 10 microm) is achieved by applying a Nd:YAG laser at 1064 nm in
      collinear double-pulse and triple-pulse mode. The ablation depth is controlled by
      adjusting the burst energy with an external electro-optical attenuator. A
      fingerprint of the depth profile is gained by measuring the LIBS signals from
      zinc, aluminium and iron as a function of the burst energy, and by post
      processing the data obtained. Up to three depths can be sampled simultaneously
      with a single laser burst by measuring the LIBS signals after each pulse within
      the laser burst. A concept for continuously monitoring the Al depth profile
      during the galvanising process is presented and applied to different hot-dip
      galvanised coatings. The method was tested on rotating sheet steel disks moving
      at a speed of up to 1 m/s. The potential and limitations of the new method are
      discussed.

PMID- 16570145
TI  - Septic shock: a heart story since the 1960s.

PMID- 16570148
TI  - Adrenal insufficiency after brain injury.

PMID- 16570146
TI  - Expanding ICU facilities in an epidemic: recommendations based on experience from
      the SARS epidemic in Hong Kong and Singapore.
AB  - Epidemics have the potential to severely strain intensive care resources and may
      require an increase in intensive care capability. Few intensivists have direct
      experience of rapidly expanding intensive care services in response to an
      epidemic. This contribution presents the recommendations of an expert group from
      Hong Kong and Singapore who had direct experience of expanding intensive care
      services in response to the epidemic of severe acute respiratory syndrome. These
      recommendations cover training, infection control, staffing, communication and
      ethical issues. The issue of what equipment to purchase is not addressed. Early
      preparations should include fit testing of negative pressure respirators,
      training of reserve staff, sourcing of material for physical modifications to the
      ICU, development of infection control policies and training programmes, and
      discussion of triage and quarantine issues.

PMID- 16570150
TI  - Cytokeratin 19 fragments in patients with acute lung injury: a preliminary
      observation.
AB  - OBJECTIVE: Cytokeratin 19 (CK19) is a specific cytoskeletal structure for
      alveolar epithelium. We hypothesized that the levels of CK19 fragments in
      bronchoalveolar lavage (BAL) fluid could serve as an index of epithelial injury
      and as a prognosis marker in patients with acute lung injury (ALI) or acute
      respiratory distress syndrome (ARDS). The aims of our study were, in patients
      with ALI/ARDS: (1) to measure CK19 fragments concentrations in BAL fluid, (2) to
      assess its prognostic value, and (3) to identify the cellular source of CK19 in
      the alveolar space. DESIGN: Prospective preliminary study. SETTING: University
      hospital surgical ICU. PATIENTS: Twenty-two mechanically ventilated patients with
      ALI/ARDS and 10 non-ventilated control patients. Plasma samples were obtained for
      11 ALI/ARDS patients. MEASUREMENTS AND RESULTS: The concentration of BAL CK19
      fragments was higher in patients (median 4916 pg/ml, 25th-75th percentile 2717
      10533) than in controls (2208 pg/ml. 767-3923; p =0.05), and higher in 10 non
      survivors (7051 pg/ml, 4372-13371) than in 12 survivors (2888 pg/ml, 1315-5639; p
      =0.03 among ALI/ARDS patients). BAL CK19 fragment concentration did not correlate
      with simplified acute physiologic score, lung injury score or PaO(2)/FIO(2)
      ratio, but correlated positively with BAL albumin concentration (p =0.002) and
      with number of BAL macrophages (p=0.0001). Plasma CK19 fragment concentrations
      were 10 times lower than those in BAL. Immunohistochemical staining for CK19
      showed a strong labelling of injured detached epithelial cells and hyperplastic
      epithelium in ALI/ARDS lung samples. CONCLUSION: CK19 fragment concentrations
      were found to be elevated in BAL fluid in ALI/ARDS patients compared with control
      subjects. High BAL CK19 fragment levels were associated with a poor prognosis.

PMID- 16570151
TI  - Acalculous cholecystitis mimicking plasma cell leukemia.

PMID- 16570149
TI  - A comparison of early gastric and post-pyloric feeding in critically ill
      patients: a meta-analysis.
AB  - OBJECTIVE: To investigate the potential beneficial and adverse effects of early
      post-pyloric feeding compared with gastric feeding in critically ill adult
      patients with no evidence of impaired gastric emptying. DESIGN: Randomised
      controlled studies comparing gastric and post-pyloric feeding in critically ill
      adult patients from Cochrane Controlled Trial Register (2005 issue 3), EMBASE and
      MEDLINE databases (1966 to 1 October 2005) without any language restriction were
      included. Two reviewers reviewed the quality of the studies and performed data
      extraction independently. MEASUREMENTS AND RESULTS: Eleven randomised controlled
      studies with a total of 637 critically ill adult patients were considered. The
      mortality (relative risk [RR] 1.01, 95% CI 0.76-1.36, p=0.93; I2=0%) and risk of
      aspiration or pneumonia (RR 1.28, 95% CI 0.91-1.80, p=0.15; I2=0%) were not
      significantly different between patients treated with gastric or post-pyloric
      feeding. The effect of post-pyloric feeding on the risk of pneumonia or
      aspiration was similar when studies were stratified into those with and those
      without the use of concurrent gastric decompression (RR ratio 0.95, 95% CI 0.48
      1.91, p=0.89). The risk of diarrhoea and the length of intensive care unit stay
      (weighted mean difference in days -1.46, 95% CI -3.74 to 0.82, p=0.21; I2=24.6%)
      were not statistically different. The gastric feeding group had a much lower risk
      of experiencing feeding tube placement difficulties or blockage (0 vs 9.6%, RR
      0.13, 95% CI 0.04-0.44, p=0.001; I2=0%). CONCLUSIONS: Early use of post-pyloric
      feeding instead of gastric feeding in critically ill adult patients with no
      evidence of impaired gastric emptying was not associated with significant
      clinical benefits.

PMID- 16570152
TI  - Bone marrow necrosis associated with the use of imatinib mesylate in a patient
      with Philadelphia chromosome-positive acute lymphoblastic leukemia.

PMID- 16570153
TI  - Effects of evaporative cooling on reproductive performance and milk production of
      dairy cows in hot wet conditions.
AB  - Fourteen animals of second and third lactation of Thai Friesian crossbred cows
      (87.5% Friesian x 12.5% Bos indicus) located at Sakol Nakhon Research and
      Breeding Centre, Department of Livestock Development, Ministry of Agriculture and
      Cooperatives, were divided randomly into two groups of seven each to evaluate the
      effects of evaporative cooling on reproductive and physiological traits under
      hot, humid conditions. Results indicated that installation of evaporating cooling
      in the open shed gave a further improvement in ameliorating heat stress in dairy
      cows in hot-wet environments by utilising the low humidity conditions that
      naturally occur during the day. The cows housed in an evaporatively cooled
      environment had both a rectal temperature and respiration rate (39.09 degrees C,
      61.39 breaths/min, respectively) significantly lower than that of the non-cooled
      cows (41.21 degrees C; 86.87 breaths/min). The former group also had higher milk
      yield and more efficient reproductive performance (pregnancy rate and reduced
      days open) than the latter group. It is suggested that the non-evaporatively
      cooled cows did not gain benefit from the naturally lower heat stress during
      night time.

PMID- 16570155
TI  - Ghrelin prevents development of diabetes at adult age in streptozotocin-treated
      newborn rats.
AB  - AIMS/HYPOTHESIS: Ghrelin, a stomach-derived hormone, functions in multiple
      biological processes, including glucose metabolism and cellular differentiation
      and proliferation. In this study, we examined whether early treatment with
      ghrelin can regenerate beta cells of the pancreas in an animal model of diabetes
      mellitus, the n0-STZ model, in which neonatal rats are injected with
      streptozotocin (STZ) at birth. METHODS: Following administration of ghrelin to n0
      STZ rats from postnatal days 2 to 8, we examined beta cell mass, mRNA expression
      levels of insulin and of pancreatic and duodenal homeobox 1 (Pdx1) gene, and
      pancreatic morphology on days 21 and 70. In addition, we investigated the effects
      of ghrelin on beta cell replication. RESULTS: By day 21, ghrelin treatment
      increased pancreatic expression of insulin and Pdx1 mRNA in n0-STZ rats. The
      number of replicating cells was also significantly increased in the ghrelin
      treated n0-STZ model. At day 70, n0-STZ rats exhibited hyperglycaemia, despite
      slight increases in plasma insulin levels. Ghrelin treatment resulted in the
      improvement of plasma glucose levels, which were associated with normal plasma
      insulin levels. Pancreatic insulin mRNA and protein levels were significantly
      increased in ghrelin-treated n0-STZ model animals. CONCLUSIONS/INTERPRETATION:
      These findings suggest that ghrelin promotes regeneration of beta cells in STZ
      treated newborn rats. Thus, early administration of ghrelin may help prevent the
      development of diabetes in disease-prone subjects after beta cell destruction.

PMID- 16570154
TI  - Genetic variation in the hepatic lipase gene and the risk of coronary heart
      disease among US diabetic men: potential interaction with obesity.
AB  - AIMS/HYPOTHESIS: The -514 C to T polymorphism of the hepatic lipase gene (LIPC)
      has been associated with lowered LIPC activity and elevated HDL-cholesterol
      concentrations. Previous findings on the association of this polymorphism with
      the risk of CHD are inconsistent. Moreover, data on this association among
      diabetic patients are limited. We investigated the association of the LIPC
      polymorphism with CHD risk among US diabetic men and evaluated whether this
      association was modified by adiposity status. SUBJECTS AND METHODS: The case
      group consisted of 220 diabetic men who were recruited from the Health
      Professionals Follow-up Study (years 1986-2000) and were free of cardiovascular
      disease at baseline, but subsequently developed CHD. A total of 641 diabetic men
      from the same study but without cardiovascular disease constituted the control
      group. RESULTS: No overall association between the LIPC polymorphism and CHD risk
      was observed. However, we did observe a significant interaction between this
      polymorphism and BMI in association with CHD risk. Among obese men, after
      adjustment for age, duration of diabetes and major lifestyle factors, the CT or
      TT genotype was associated with an increased CHD risk compared with the CC
      genotype (odds ratio [OR] 2.52, 95% CI 1.08-5.90); the corresponding ORs (95% CI)
      were 0.99 (0.58, 1.69) for overweight men (25< or =BMI <30 kg/m(2)) and 0.37
      (0.17, 0.79) for lean men (BMI <25 kg/m(2)) (p for interaction 0.001). Stratified
      analyses by waist circumference (tertiles) showed a similar pattern of
      interaction (adjusted p for interaction 0.023). CONCLUSION/INTERPRETATION: These
      data suggest that obesity may modify the association between the LIPC C(-514)T
      polymorphism and CHD risk among diabetic men.

PMID- 16570157
TI  - Enhanced soluble CD40L in patients with the metabolic syndrome: Relationship with
      in vivo thrombin generation.
AB  - AIMS/HYPOTHESIS: The metabolic syndrome is associated with proinflammatory and
      prothrombotic states. This study was designed to assess the behaviour of soluble
      CD40 ligand (sCD40L) and prothrombin fragment F (1+2), a marker of thrombin
      generation, in patients with the metabolic syndrome. METHODS: We investigated 106
      patients with the metabolic syndrome, diagnosed according to the ATPIII report,
      and 104 subjects without the metabolic syndrome. RESULTS: Plasma values of sCD40L
      and F (1+2) were higher in patients with the metabolic syndrome (4.11+/-1.64 vs
      2.61+/-0.89 ng/ml and 1.54+/-0.49 vs 0.87+/-0.21 nmol/l, respectively; p < 0.001)
      and were significantly correlated (r = 0.925, p < 0.001). Stepwise multiple
      linear regression analysis showed that sCD40L was significantly associated with F
      (1+2), female sex and waist circumference. CONCLUSIONS/INTERPRETATION: Patients
      with the metabolic syndrome have enhanced values of plasma sCD40L and F (1+2).
      The study provides further insight into the relationship between metabolic
      syndrome, inflammation and thrombosis.

PMID- 16570158
TI  - Secular trends in the prevalence of diabetes and impaired glucose tolerance in
      urban South India--the Chennai Urban Rural Epidemiology Study (CURES-17).
AB  - AIMS/HYPOTHESIS: The aim of this study was to determine the secular trends in
      prevalence of diabetes and IGT in urban India. MATERIALS AND METHODS: The Chennai
      Urban Rural Epidemiology Study (CURES) screened 26,001 individuals aged > or =20
      years using the American Diabetes Association fasting capillary glucose criteria.
      The study population, which was representative of Chennai, was recruited by
      systematic random sampling. Every tenth subject from Phase 1 of CURES was invited
      to participate in Phase 3 for screening by World Health Organization (WHO) plasma
      glucose criteria. The response rate was 90.4% (2,350 responders from 2,600
      potential subjects). The prevalences of diabetes and IGT in CURES were compared
      with three earlier studies: two conducted on a representative population of
      Chennai in 1989 and 1995, and the other the National Urban Diabetes Survey (NUDS)
      completed in 2000. RESULTS: The overall crude prevalence of diabetes using WHO
      criteria in CURES was 15.5% (age-standardised 14.3%), while that of IGT was 10.6%
      (age-standardised 10.2%). Prevalence of diabetes increased by 39.8% (8.3-11.6%)
      from 1989 to 1995; by 16.3% (11.6-13.5%) between 1995 and 2000; and by 6.0% (13.5
      14.3%) between 2000 and 2004. Thus within a span of 14 years, the prevalence of
      diabetes increased by 72.3% (chi (2) trend 22.23, p < 0.0001). The prevalence of
      IGT increased by 9.6% from 1989 to 1995 and by 84.6% between 1995 and 2000 (chi 2
      trend 52.9, p < 0.0001). However, it decreased by 39.3% between 2000 and 2004 (p
      < 0.0001). There was a shift in the age at diagnosis of diabetes to a younger age
      in CURES compared with NUDS. CONCLUSIONS/INTERPRETATION: Compared with earlier
      studies, the prevalence of diabetes in Chennai, representing urban India, has
      increased while that of IGT has decreased.

PMID- 16570159
TI  - The influence of genetic background on the induction of oxidative stress and
      impaired insulin secretion in mouse islets.
AB  - AIMS/HYPOTHESIS: We determined whether high-glucose-induced beta cell dysfunction
      is associated with oxidative stress in the DBA/2 mouse, a mouse strain
      susceptible to islet failure. MATERIALS AND METHODS: Glucose- and non-glucose
      mediated insulin secretion from the islets of DBA/2 and control C57BL/6 mice was
      determined following a 48-h exposure to high glucose. Flux via the hexosamine
      biosynthesis pathway was assessed by determining O-glycosylated protein levels.
      Oxidative stress was determined by measuring hydrogen peroxide levels and the
      expression of anti-oxidant enzymes. RESULTS: Exposure to high glucose levels
      impaired glucose-stimulated insulin secretion in DBA/2 islets but not C57BL/6
      islets, and this was associated with reduced islet insulin content and lower ATP
      levels than in C57BL/6 islets. Exposure of islets to glucosamine for 48 h
      mimicked the effects of high glucose on insulin secretion in the DBA/2 islets.
      High glucose exposure elevated O-glycosylated proteins; however, this occurred in
      islets from both strains, excluding a role for O-glycosylation in the impairment
      of DBA/2 insulin secretion. Additionally, both glucosamine and high glucose
      caused an increase in hydrogen peroxide in DBA/2 islets but not in C57BL/6
      islets, an effect prevented by the antioxidant N-acetyl-L: -cysteine.
      Interestingly, while glutathione peroxidase and catalase expression was
      comparable between the two strains, the antioxidant enzyme manganese superoxide
      dismutase, which converts superoxide to hydrogen peroxide, was increased in DBA/2
      islets, possibly explaining the increase in hydrogen peroxide levels.
      CONCLUSIONS/INTERPRETATION: Chronic high glucose culture caused an impairment in
      glucose-stimulated insulin secretion in DBA/2 islets, which have a genetic
      predisposition to failure, and this may be the result of oxidative stress.

PMID- 16570160
TI  - Induction of adiponectin in skeletal muscle of type 2 diabetic mice: In vivo and
      in vitro studies.
AB  - AIMS/HYPOTHESIS: Adiponectin is an adipokine that exhibits insulin-sensitising,
      fat-burning and anti-inflammatory properties as well as modulatory effects on
      oxidative stress. We examined whether adiponectin could be induced in a non
      adipose tissue, skeletal muscle, in response to metabolic or oxidative aggression
      both in vivo (in a murine model of type 2 diabetes) and in vitro. METHODS: Obese
      and diabetic ob/ob mice were used and compared with lean littermates. Some obese
      mice were treated with the antioxidant probucol for 3 weeks. At the end of the
      experiment, blood was sampled and tibialis anterior muscles were collected for
      mRNA measurement and immunohistochemistry. Additional in vitro experiments were
      performed on C2C12 myotubes cultured for up to 48 h. RESULTS: In spite of
      hypoadiponectinaemia, Adipoq mRNA levels were markedly increased in the skeletal
      muscle of ob/ob mice and correlated with systemic oxidative stress. Adipoq
      upregulation was shown in laser-microdissected myocytes of obese mice.
      Concomitantly, immunoreactivity for adiponectin was enhanced in obese muscle
      fibres together with lipid infiltration and local markers of oxidative stress. In
      cultured C2C12 myotubes, a triglyceride mix and reactive oxygen species producers
      (H2O2 or a lipoperoxidation end-product) upregulated Adipoq expression and
      adiponectin production. This effect was reversed by an antioxidant. Finally,
      treatment of obese mice with probucol also attenuated upregulation in muscle.
      CONCLUSIONS/INTERPRETATION: The paradoxical upregulation of adiponectin in muscle
      of obese and diabetic mice may result from lipotoxicity and related oxidative
      stress. This unexpected finding could be viewed as a local protection to
      counteract ectopic fat deposition and oxidative damage.

PMID- 16570161
TI  - Intracellular amyloid-like deposits contain unprocessed pro-islet amyloid
      polypeptide (proIAPP) in beta cells of transgenic mice overexpressing the gene
      for human IAPP and transplanted human islets.
AB  - AIMS/HYPOTHESIS: Islet amyloid is a frequent finding in the islets of Langerhans
      of individuals with type 2 diabetes. The main amyloid constituent is the beta
      cell-derived polypeptide hormone islet amyloid polypeptide (IAPP). In general,
      amyloid refers to an extracellular deposit of a congophilic material, but
      intracellular amyloid is seen in some beta cells of transgenic mice expressing
      the gene for human IAPP and in human islets transplanted into nude mice. The aim
      of this study was to immunohistochemically characterise the intracellular
      amyloid. METHODS: Antisera against the N- and C-terminal processing sites of
      proIAPP (which were therefore specific for proIAPP), the C-terminal flanking
      peptide and mature IAPP were used for immunoelectron microscopy. RESULTS:
      Fibrillar aggregates were seen in the halo region of the secretory granules in
      some beta cells in human IAPP transgenic mice. These aggregates were labelled
      with proIAPP-specific antisera. Also, proIAPP reactivity was more widespread in
      the intracellular amyloid-like aggregates in beta cells of transgenic mice than
      in human islet transplants, in which the intracellular amyloid-like deposits were
      larger, but the proIAPP labelling was restricted to small spots within the
      amyloid deposits. CONCLUSIONS/INTERPRETATION: We suggest that proIAPP forms the
      first amyloid fibrils and that this can occur already in the secretory granules
      of the beta cells. The proIAPP-derived fibrils can act as seed for further
      amyloid formation, now made up by IAPP. The observed difference between human
      islet transplants and human IAPP transgenic animals may reflect differences in
      stages of amyloid development.

PMID- 16570162
TI  - Secretion of adiponectin by human placenta: differential modulation of
      adiponectin and its receptors by cytokines.
AB  - AIMS/HYPOTHESIS: Pregnancy, a state of insulin resistance, is associated with
      elevated levels of cytokines and profound alterations in metabolism. Serum
      adiponectin, an adipokine with anti-inflammatory and insulin-sensitising
      properties, has been shown to be lower in patients with gestational diabetes
      mellitus, a state of greater insulin resistance than normal pregnancies.
      Hypothesising that the human placenta is a source of adiponectin, we investigated
      its expression and secretion, and the regulation by cytokines of adiponectin and
      its receptors. METHODS: Real-time RT-PCR, radioimmunoassay, Western blotting,
      radioligand binding and immunofluorescent analyses were applied to demonstrate
      the expression, secretion and functionality of placental adiponectin. RESULTS:
      Adiponectin gene expression and protein were found in the human term placenta,
      with expression primarily in the syncytiotrophoblast. RIA of conditioned media
      from explant experiments revealed that the placenta can secrete adiponectin in
      vitro. Addition of conditioned media to HEK-293 cells transfected with the gene
      for adiponectin receptor-1 (ADIPOR1) altered the phosphorylation status of
      extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein
      kinase, an effect abolished after preabsorption with adiponectin antibody.
      Cytokines, including TNF-alpha, IFN-gamma, IL-6 and leptin, differentially
      modulated placental adiponectin receptors as well as adiponectin gene expression
      and secretion. Interestingly, in placentae from women with gestational diabetes
      mellitus, we observed significant downregulation of adiponectin mRNA, significant
      upregulation of ADIPOR1 expression, and a non-significant increase in ADIPOR2
      expression. CONCLUSIONS/INTERPRETATION: Our results indicate that the human
      placenta produces and secretes adiponectin, and that adiponectin and its
      receptors are differentially regulated by cytokines and their expression altered
      in women with gestational diabetes mellitus. Collectively, our novel data suggest
      that adiponectin may play a role in adapting energy metabolism at the materno
      fetal interface.

PMID- 16570163
TI  - Tissue selectivity of insulin detemir action in vivo.
AB  - AIMS/HYPOTHESIS: Recombinant DNA technology is a useful tool that can be used to
      create insulin analogues with modified absorption kinetics to improve glycaemic
      control in patients with type 1 and type 2 diabetes. Among conventional insulin
      analogues, which are usually created by amino acid exchange, insulin detemir is
      the first analogue to be acylated with a fatty acid to enable reversible albumin
      binding. In this study we determined activation of the insulin receptor (IR)
      signalling cascade by insulin detemir at the level of IR and IR substrate (Irs)
      phosphorylation, as well as downstream signalling elements such as
      phosphatidylinositol 3-kinase and Akt, and performed epidural EEG in vivo.
      METHODS: C57Bl/6 mice were injected i.v. with either insulin detemir or human
      insulin and Western blot analysis was performed on liver, muscle, hypothalamic
      and cerebrocortical tissues. Moreover, cerebrocortical activity was detected by
      EEG in awake mice and cerebral insulin concentrations were measured following
      human insulin and insulin detemir injection. RESULTS: The time course and extent
      of IR phosphorylation in peripheral tissues were similar following insulin
      detemir treatment compared with human insulin, but insulin signalling in
      hypothalamic and cerebrocortical tissue determined by tyrosine-phosphorylation of
      the IR and Irs2 proteins occurred faster and was enhanced due to a higher insulin
      detemir concentration in the brain. Moreover, epidural EEG in mice displayed
      increased cortical activity using insulin detemir. CONCLUSIONS/INTERPRETATION:
      Taken together, these data suggest that insulin detemir has a tissue-selective
      action, with a relative preference for brain compared with peripheral tissues.

PMID- 16570164
TI  - Sex- and season-dependent differences in C-peptide levels at diagnosis of immune
      mediated type 1 diabetes.
AB  - AIMS/HYPOTHESIS: The incidence of type 1 diabetes varies according to age, sex
      and season of diagnosis. We investigated whether these and other clinical,
      biological and anthropometric parameters were correlated with residual beta cell
      function in newly diagnosed patients, since it is possible that the nature of
      external and/or genetic disease accelerators may be (partly) reflected in the
      inaugural disease presentation. MATERIALS AND METHODS: The correlates of random C
      peptide levels sampled shortly after diagnosis (median [interquartile range]: 3
      [0-14] days) were studied by multivariate analysis in 1,883 islet-antibody
      positive diabetic patients aged <40 years who were diagnosed between 1989 and
      2000. RESULTS: Higher C-peptide levels (above percentile 50 of patients) were
      associated with older age at diagnosis, female sex, diagnosis in the high
      incidence season (October to March), less-decreased BMI (expressed as a standard
      deviation score), lower insulin requirements after stabilisation, lower
      prevalence of ketonuria and a less-increased glycaemia at diagnosis (all p <
      0.001). C-peptide levels were not correlated with calendar year at diagnosis,
      duration of symptoms prior to diagnosis, HLA-DQ2/DQ8 genotype or islet antibody
      status. CONCLUSIONS/INTERPRETATION: Sex- and season-dependent differences in
      residual functional beta cell mass and/or insulin resistance have been identified
      at diagnosis of type 1 diabetes. They may reflect differences in disease
      precipitating external or lifestyle factors and should be further investigated
      longitudinally in prediabetes to further identify putative aetiological factors,
      which may provide targets for prevention.

PMID- 16570165
TI  - Prenatal programming of hepatocyte nuclear factor 4alpha in the rat: A key
      mechanism in the 'foetal origins of hyperglycaemia'?
AB  - AIMS/HYPOTHESIS: Prenatal glucocorticoid exposure causes lifelong hyperglycaemia
      in rat offspring, associated with permanently increased hepatic
      phosphoenolpyruvate carboxykinase 2 (PCK2), the rate-controlling enzyme of
      gluconeogenesis. To elucidate the mechanisms underlying the 'programming' of
      PCK2, this study examined the effect of prenatal dexamethasone treatment on
      expression of transcription factors that regulate Pck2. MATERIALS AND METHODS:
      Real-time RT-PCR and in situ hybridisation were used to measure and localise
      hepatic mRNA transcribed from the genes for PCK2, hepatocyte nuclear factor 4,
      alpha (HNF4A), transcription factor 1 (TCF1), CCAAT/enhancer binding protein,
      alpha (CEBPA), CEBPB, the glucocorticoid receptor (NR3C1) and peroxisome
      proliferative activated receptor, gamma, coactivator 1 alpha (PPARGC1A) in foetal
      and adult offspring of dams treated with dexamethasone or vehicle during the last
      week of gestation. RESULTS: Prenatal dexamethasone exposure significantly
      elevated Hnf4a mRNA expression in foetal and adult liver. This resulted from
      increased expression of isoforms derived from the 'adult' (P1) Hnf4a promoter. In
      contrast, isoforms from the 'foetal' (P2) promoter were markedly suppressed by
      dexamethasone. Like Pck2, the increase in hepatic Hnf4a mRNA occurred exclusively
      in the periportal zone. Foetal Tcf1 expression was also increased by
      dexamethasone treatment, but this did not persist into adulthood. Prenatal
      dexamethasone did not affect the amounts of foetal and/or adult Cebpa, Cebpb,
      Nr3c1 or Ppargc1a mRNA. CONCLUSIONS/INTERPRETATION: Prenatal dexamethasone
      exposure caused a permanent increase in hepatic Hnf4a mRNA. This increase, which
      was associated with a premature switch from foetal to adult promoter
      predominance, was congruent with changes in Pck2 expression. These data suggest
      that HNF4A might mediate Pck2 overexpression and subsequent hyperglycaemia.

PMID- 16570167
TI  - [Control of methicillin-resistant S. aureus by active surveillance. Results of a
      workshop held by the Deutsche Gesellschaft fur Hygiene und Mikrobiologie].
AB  - In Germany, methicillin-resistant S. aureus (MRSA) is increasing continuously. To
      control the spread of MRSA, active surveillance and admission screening are
      recommended. In most cases, screening cultures of patients at risk for MRSA will
      be sufficient. Screening of all patients admitted to an ICU is cost-effective
      when the incidence of MRSA and nosocomial MRSA infections is high (>2 cases/100
      patients and 0.3 MRSA infections/100 patients, respectively): Under these
      circumstances, a decrease in the incidence of nosocomial MRSA infections of 50%
      leads to cost-effectiveness at costs of 16 Euro/sample (including subsequent
      costs). If the incidence of nosocomial MRSA infections decreases by 75%, costs of
      24 Euro/sample (including subsequent costs) are cost-effective. If the incidence
      of MRSA is high, screening by PCR may be cost-effective for patients at high risk
      for MRSA, especially if they are isolated prophylactically. Recently, PCR methods
      have been developed which allow the specific identification of MRSA even from
      nasal swabs.

PMID- 16570168
TI  - [Perioperative fluid management: A relay race of knowledge].

PMID- 16570169
TI  - Marginal fractures of the medial tibial plateau: possible association with medial
      meniscal root tear.
AB  - We report two cases of marginal fractures of the medial tibial plateau associated
      with medial meniscal root tears. Both patients sustained knee dislocations, with
      complete tears of the posterior horn medial meniscal root. One sustained a
      "reverse Segond fracture"; the other sustained an "anteromedial impingement
      fracture" of the tibial plateau. The meniscal root tears were arthroscopically
      confirmed and repaired. In the first patient, the integrity of the meniscal root
      repair was confirmed at a 6-month follow-up arthroscopy for lysis of adhesions.
      In the second patient, follow-up MRI at 10 months demonstrated a healed meniscal
      root. The association of medial meniscal root tear with marginal fractures of the
      medial tibial plateau has not been previously reported.

PMID- 16570166
TI  - Apolipoprotein AV does not contribute to hypertriglyceridaemia or triglyceride
      lowering by dietary fish oil and rosiglitazone in obese Zucker rats.
AB  - AIMS/HYPOTHESIS: Apolipoprotein AV (apoAV) is a recently discovered
      apolipoprotein with a triglyceride-lowering effect in genetically modified mice.
      Transcription of the human gene encoding apoAV (APOA5) is suppressed by insulin
      and stimulated by fibrates. Our goal was to study the expression of Apoa5, in
      comparison with Apoa4 and Apoc3, in hypertriglyceridaemic, obese and insulin
      resistant Zucker rats receiving the insulin sensitiser rosiglitazone and/or a
      fish oil diet to lower triglycerides. METHODS: Hepatic Apoa5, Apoa4 and Apo3 mRNA
      and liver and plasma apoAV were measured in lean and obese Zucker rats receiving
      rosiglitazone while on a coconut oil or fish oil diet. RESULTS: Basal hepatic
      Apoa5 expression was similar in obese and lean Zucker rats. Unexpectedly, obese
      Zucker rats tended to have higher plasma apoAV levels despite their
      hypertriglyceridaemic state. Both rosiglitazone and the fish oil diet
      significantly increased Apoa5 mRNA, by about 70%, but tended to lower liver and
      plasma apoAV. Rosiglitazone had no effect on Apoa5 mRNA in cultured rat
      hepatocytes. No intact PPAR (peroxisome proliferator-activated receptor) response
      element was identified in the rat Apoa5 promoter. CONCLUSIONS/INTERPRETATION: Our
      data indicate that apoAV does not contribute to the hypertriglyceridaemia of
      obese Zucker rats or to the hypolipidaemic effect of rosiglitazone or a fish oil
      diet. The divergent changes of Apoa5 mRNA and apoAV levels suggest co- or post
      translational regulation. The increase in Apoa5 mRNA induced by rosiglitazone is
      not directly mediated by peroxisome proliferator-activated receptor gamma.

PMID- 16570170
TI  - Computed tomography analysis of acetabular anteversion and abduction.
AB  - PURPOSE: The purpose of this study is to define the normal range of acetabular
      abduction and anteversion in relation to pelvic anatomy as depicted on
      conventional CT scan. METHODS: We retrospectively reviewed 100 pelvic CT scans
      performed on patients presenting for evaluation of non-orthopaedic pathology. The
      study group consisted of 58 women and 42 men, aged between 18 and 88 years.
      Standard imaging protocol included an anteroposterior (AP) topogram with
      contiguous 5-mm thick axial images from the superior margin of the iliac crest to
      the lesser trochanter of the femur. The acetabular abduction was measured from
      the AP topogram by obtaining the angle between a line drawn from the acetabular
      teardrop to the lateral acetabular margin and a horizontal line between the
      ischial tuberosities. Acetabular anteversion was measured on axial images at the
      level of the mid-femoral head. RESULTS: We found the mean acetabular abduction to
      be 39 degrees (standard deviation 4 degrees, range 27 to 51 degrees) and the mean
      acetabular anteversion to be 23 degrees (standard deviation 5 degrees, range 12
      to 39 degrees). Data suggests that acetabular anteversion may average 2.7 degrees
      lower in males than females and increase slightly with age, while abduction may
      tend to decrease with age. Ninety percent of patients had acetabular abduction
      between 31 and 46 degrees; the 90% central range for acetabular anteversion was
      estimated to be from 14 to 31 degrees. CONCLUSION: CT scanning is useful in
      accurately defining the normal range of acetabular abduction and antiversion.
      Knowledge of this normal anatomy will allow accurate assessment of acetabular
      component position as delineated on conventional CT scanning.

PMID- 16570171
TI  - Sonography of the iliopsoas tendon and injection of the iliopsoas bursa for
      diagnosis and management of the painful snapping hip.
AB  - OBJECTIVE: The purpose of this study was to compare sonographic evaluations of
      patients referred with suspected snapping of their iliopsoas tendon with the pain
      relief achieved from anesthetic injection of the iliopsoas bursa, and with the
      subsequent surgical outcome. This study also assessed the effectiveness of
      Kenalog injection into the iliopsoas bursa for long-term pain relief. PATIENTS
      AND METHODS: Dynamic and static sonography was performed in 40 patients with
      clinically diagnosed snapping hips. The iliopsoas bursa was injected with
      Bupivicaine and Lidocaine in the first 22 patients, and an additional 1 ml
      Kenalog-40 was added to this mixture in the last 18 patients. We compared the
      static and dynamic sonographic findings with change in the patients' level of
      pain at 2 days after anesthetic injection. The sonographic findings and response
      to anesthetic injection were also compared to the response to Kenalog injection
      and the results of any subsequent surgery. RESULTS: Static sonography of the
      iliopsoas tendon was normal in 38 patients, and detected iliopsoas bursitis in
      one patient and iliopsoas tendinopathy in another. Snapping of the iliopsoas
      tendon was observed using dynamic sonography in 9 of the 40 patients. Following
      anesthetic injection of the iliopsoas bursa, 29 patients had complete or partial
      pain relief, and 11 patients had no pain relief. Eight of the nine patients with
      a snapping iliopsoas tendon had complete or partial pain relief from the bursal
      injection. Twelve of the 29 patients with pain relief after anesthetic injection
      later had an arthroscopic iliopsoas tendon release, and all of these 12 patients
      had a good postoperative result. Of the 18 patients who had Kenalog-40 injected
      into the iliopsoas bursa and did not have iliopsoas surgery, 16 had sustained
      pain relief following the injection. CONCLUSIONS: Patients with groin pain and a
      clinically suspected snapping iliopsoas tendon can benefit from injection into
      the iliopsoas bursa even if the snapping tendon is not visualized
      sonographically. The use of a corticosteroid may provide long-term pain relief,
      and pain relief after injection is a predictor of good outcome after surgical
      release of the iliopsoas tendon.

PMID- 16570173
TI  - International anatomical terminology.

PMID- 16570172
TI  - MR imaging findings of acetabular dysplasia in adults.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of MR imaging in the
      identification of labral and articular cartilage lesions in patients with
      acetabular dysplasia. DESIGN AND PATIENTS: Pre-operative MR imaging was performed
      on 27 hips in 25 consecutive patients (16 males, 9 females, age range 19-52
      years, mean age 31.2 years) with radiographic evidence of acetabular dysplasia
      (centre-edge angle of Wiberg <20 degrees). The average duration of symptoms was
      16.2 months. Two musculoskeletal radiologists assessed MR images in consensus for
      the presence of abnormality involving the acetabular labrum and adjacent
      acetabular articular cartilage. A high resolution, non-arthrographic technique
      was used to assess the labrum and labral chondral transitional zone. Surgical
      correlation was obtained in all cases by a single surgeon experienced in hip
      arthroscopy and ten patients with normal hip MRI were included to provide a
      control group. RESULTS: The acetabular labra in the dysplastic hips demonstrated
      abnormal signal intensity, and had an elongated appearance when compared with the
      control group (mean length 10.9 mm vs 6.4 mm). Morphological appearances in the
      labra included surface irregularity, fissures and cleft formation. MR imaging
      correctly identified the severity of chondral abnormality in 24 of 27 hips (89%)
      when compared with arthroscopic findings. CONCLUSIONS: MR imaging demonstrates an
      elongated labrum, focal intra-substance signal change and irregularity and
      fissuring of the margins in patients with acetabular dysplasia. Abnormality is
      also identified at the labral chondral transitional zone, where fissuring, focal
      clefts, chondral deficiency and subchondral cyst formation may be apparent. A
      high-resolution, non-arthrographic technique can provide an accurate preoperative
      assessment and evaluate the presence of premature osteoarthritis.

PMID- 16570174
TI  - Is Paget's disease of bone disappearing?

PMID- 16570175
TI  - Flexor carpi radialis tendinopathy: spectrum of imaging findings and association
      with triscaphe arthritis.
AB  - OBJECTIVE: To present the spectrum of pathology affecting the flexor carpi
      radialis (FCR), and its anatomical, functional and clinical relationship with
      conditions affecting the triscaphe or scapho-trapezium-trapezoid (STT)
      compartment, and particularly osteoarthritis. DESIGN: The study comprised two men
      and four women aged between 23 and 79 years (mean age, 49 years). Two
      musculoskeletal radiologists in consensus evaluated MRI findings. RESULTS: Five
      of the patients showed evidence of triscaphe osteoarthritis. One of the patients
      showed synovitis and reactive marrow edema at the triscaphe joint without more
      specific findings of osteoarthritis. Five patients showed evidence of FCR
      tenosynovitis. Partial-thickness tears were noted in three patients. Two patients
      showed complete discontinuity of the FCR; one of them had undergone prior tendon
      harvesting for interposition arthroplasty after trapezectomy. One patient showed
      a ganglion cyst in connection to the FCR tendon sheath. CONCLUSION: The FCR
      tendon courses over the volar surfaces of the scaphoid and trapezium in a
      separate fibro-osseous tunnel. This anatomical and functional relationship
      explains the coexistence of FCR tendinopathy and STT arthritis demonstrated by MR
      imaging.

PMID- 16570176
TI  - The reverse shoulder prosthesis: A review of imaging features and complications.
AB  - BACKGROUND: The reverse shoulder prosthesis is a prosthesis that has been in
      clinical use in Europe since 1985 and was approved for use in the United States
      in 2004. This unique prosthesis has a baseplate attached to the glenoid, which
      holds a spherical component, while the humeral component includes a polyethylene
      insert that is flat. This design is the "reverse" configuration of that seen with
      a conventional arthroplasty, in which the spherical component is part of the
      humeral component. The indications for the reverse prosthesis are: (1) painful
      arthritis associated with irreparable rotator cuff tears (cuff tear arthropathy),
      (2) failed hemiarthroplasty with irreparable rotator cuff tears, (3)
      pseudoparalysis due to massive, irreparable rotator cuff tears, (4) some
      reconstructions after tumor resection, and (5) some fractures of the shoulder not
      repairable or reconstructable with other techniques. This prosthesis can produce
      a significant reduction in pain and some improvement in function for most of the
      indications mentioned. However, the unique configuration and the challenge of its
      insertion can result in a high incidence of a wide variety of unusual
      complications. Some of these complications, such as dislocation of the
      components, are similar to conventional shoulder replacement. Other
      complications, such as notching of the scapula and acromial stress fractures, are
      unique to this prosthesis. CONCLUSION: The configuration of the reverse
      prosthesis, its normal radiographic appearance and potential complications
      associated with its use are reviewed.

PMID- 16570178
TI  - Bilateral aplasia of the tibialis anterior and unilateral aplasia of the extensor
      hallucis longus muscles.
AB  - A 35-year-old woman presented with bilateral leg pain on walking that had been
      present since childhood. Clinical examination showed bilateral absence of the
      tibialis anterior tendons and the left extensor hallucis longus tendon. Magnetic
      resonance imaging revealed that signal intensities in the location of the
      tibialis anterior muscles bilaterally and the left extensor hallucis longus
      muscle were uniformly high on T1-weighted images, consistent with fat tissue and
      aplastic muscles: findings not previously reported.

PMID- 16570177
TI  - Myopericytoma in Kager's fat pad.
AB  - Myopericytoma is a recently described, rare, soft-tissue tumour with perivascular
      differentiation of myoid cells. We present a case of myopericytoma occurring
      around the ankle in a 68-year old man. The patient presented with a history of a
      lump around the ankle of 4 years' duration. Clinical presentation, radiological
      features and histopathologic findings of this case are reported, and the relevant
      literature is reviewed.

PMID- 16570179
TI  - Avoiding spurious submovement decompositions II: a scattershot algorithm.
AB  - Evidence for the existence of discrete submovements underlying continuous human
      movement has motivated many attempts to "extract" them. Although they produce
      visually convincing results, all of the methodologies that have been employed are
      prone to produce spurious decompositions. In previous work, a branch-and-bound
      algorithm for submovement extraction, capable of global nonlinear minimization,
      and hence, capable of avoiding spurious decompositions, was presented [Rohrer and
      Hogan (Biol Cybern 39:190-199, 2003)]. Here, we present a scattershot-type global
      nonlinear minimization algorithm that requires approximately four orders of
      magnitude less time to compute. A sensitivity analysis reveals that the
      scattershot algorithm can reliably detect changes in submovement parameters over
      time, e.g., over the course of neuromotor recovery.

PMID- 16570180
TI  - Expression patterns of dysadherin and E-cadherin in lymph node metastases of
      colorectal carcinoma.
AB  - Reduction/loss of E-cadherin is associated with the development and progression
      of many epithelial tumors, while in a limited number of neoplasms, E-cadherin is
      re-expressed in metastases. Dysadherin, recently characterized by members of our
      research team, has an anti-cell-cell adhesion function and downregulates E
      cadherin in a posttranscriptional manner. Colorectal cancer (CRC) is one of the
      most common tumors in the developed world, and lymph node metastases are
      harbingers of aggressive behavior. The aim of the present study was to examine
      the dysadherin and E-cadherin expression patterns in lymph node metastases vs
      primary CRC. Dysadherin and E-cadherin expression was examined
      immunohistochemically in 78 patients with CRC, Dukes' stage C in the primary
      tumor and in one lymph node metastasis. Dysadherin was expressed in 42% while E
      cadherin immunoreactivity was reduced in 45% of primary tumors. In lymph nodes,
      33 and 81% of metastatic tumors were positive for dysadherin and E-cadherin,
      respectively. Dysadherin expression was not correlated with E-cadherin expression
      in the primary tumor with a reverse correlation evident in the lymph node
      metastases. Our results suggest that different mechanisms govern E-cadherin
      expression in the primary tumor and the corresponding lymph node metastases.

PMID- 16570181
TI  - Combined adenosquamous and large-cell neuroendocrine carcinoma of the
      gallbladder.

PMID- 16570183
TI  - Crystal structure of yeast Sco1.
AB  - The Sco family of proteins are involved in the assembly of the dinuclear CuA site
      in cytochrome c oxidase (COX), the terminal enzyme in aerobic respiration. These
      proteins, which are found in both eukaryotes and prokaryotes, are characterized
      by a conserved CXXXC sequence motif that binds copper ions and that has also been
      proposed to perform a thiol:disulfide oxidoreductase function. The crystal
      structures of Saccharomyces cerevisiae apo Sco1 (apo-ySco1) and Sco1 in the
      presence of copper ions (Cu-ySco1) were determined to 1.8- and 2.3-A resolutions,
      respectively. Yeast Sco1 exhibits a thioredoxin-like fold, similar to that
      observed for human Sco1 and a homolog from Bacillus subtilis. The Cu-ySco1
      structure, obtained by soaking apo-ySco1 crystals in copper ions, reveals an
      unexpected copper-binding site involving Cys181 and Cys216, cysteine residues
      present in ySco1 but not in other homologs. The conserved CXXXC cysteines, Cys148
      and Cys152, can undergo redox chemistry in the crystal. An essential histidine
      residue, His239, is located on a highly flexible loop, denoted the Sco loop, and
      can adopt positions proximal to both pairs of cysteines. Interactions between
      ySco1 and its partner proteins yeast Cox17 and yeast COX2 are likely to occur via
      complementary electrostatic surfaces. This high-resolution model of a eukaryotic
      Sco protein provides new insight into Sco copper binding and function.

PMID- 16570182
TI  - The enigmatic nature of apocrine breast lesions.
AB  - Epithelial cells of fetal breast glandular structures, at the third trimester of
      pregnancy (28 weeks), produce GCDFP-15, in the absence of specific apocrine
      morphology. Apocrine epithelium of the breast may be a normal process of
      differentiation rather than a result of metaplasia, and it has been demonstrated
      that it is estrogen-receptor, progesterone-receptor and bcl-2 negative, but
      androgen-receptor (AR) positive. The significance of AR expression in apocrine
      epithelium is uncertain. Apocrine epithelium is seen in a wide spectrum of breast
      entities, ranging from benign lesions to invasive carcinoma. Breast cancer
      accounts 32% of all cancer cases among women and is the most common type of
      cancer in women. Little is known about breast carcinogenesis. Widely, it is
      accepted that breast cancer, like most other type of cancer, is being developed
      through the accumulation of genetic aberrations. Apocrine epithelium may reflect
      instability of the breast epithelium, creating an environment favouring further
      oncogenic alterations. In the last decade, several lines of evidence support the
      idea that some breast benign epithelial apocrine lesions are clonal lesions and
      may be considered as truly pre-malignant or precursors of breast carcinoma.
      Apocrine changes in many cases do not present any diagnostic difficulty; on the
      other hand, apocrine proliferations with cytologic atypia can be particularly
      difficult and challenging. The purpose of this study is to collect and highlight
      the areas of consensus in the literature as well as the controversial areas
      concerning the apocrine epithelium of the breast.

PMID- 16570184
TI  - pH-dependent structural change of reduced spinach plastocyanin studied by
      perturbed angular correlation of gamma-rays and dynamic light scattering.
AB  - In this study the pH-dependent structural changes of reduced spinach plastocyanin
      were investigated using perturbed angular correlation (PAC) of gamma-rays and
      dynamic light scattering (DLS). PAC data of Ag-substituted plastocyanin indicated
      that the coordinating ligands are two histidine residues (His37, His87) and a
      cysteine residue (Cys84) in a planar configuration, whereas the methionine
      (Met92) found perpendicular to this plane is not a coordinating ligand at neutral
      pH. Two slightly different conformations with differences in the Cys-metal ion
      His angles could be observed with PAC spectroscopy. At pH 5.3 a third
      coordination geometry appears which can be explained as the absence of the His87
      residue and the coordination of Met92 as a ligand. With DLS the aggregation of
      reduced plastocyanin could be observed below pH 5.3, indicating that not only the
      metal binding site but also the aggregation properties of the protein change upon
      pH reduction. Both the structural changes at the metal binding site and the
      aggregation are shown to be reversible. These results support the hypothesis that
      the pH of the thylakoid lumen has to remain moderate during steady-state
      photosynthesis and indicate that low pH induced aggregation of plastocyanin might
      serve as a regulatory switch for photosynthesis.

PMID- 16570185
TI  - Quantitative assessment of SSTR2 expression in patients with non-small cell lung
      cancer using(68)Ga-DOTATOC PET and comparison with (18)F-FDG PET.
AB  - PURPOSE: Dynamic PET studies with(68)Ga-DOTATOC were performed in patients with
      non-small cell lung cancer (NSCLC) to assess the somatostatin receptor 2 (SSTR2)
      expression. Furthermore, dynamic(18)F-fluorodeoxyglucose (FDG) studies were
      performed in the same patients to compare the SSTR2 expression with the tumour
      viability. METHODS: The study population comprised nine patients, examined with
      both tracers on two different days within 1 week. Standardised uptake values
      (SUVs) were calculated and a two-tissue compartment model was applied to the
      data. Furthermore, a non-compartment model based on the fractal dimension (FD)
      was applied to the data. RESULTS: The DOTATOC uptake was generally lower than the
      FDG uptake. Moderately enhanced DOTATOC uptake was noted in seven of the nine
      tumours. All kinetic parameters except k (4) were lower for DOTATOC than for FDG.
      The mean SUV was 2.018 for DOTATOC, in comparison to 5.683 for FDG. In
      particular, k (3) was highly variable for DOTATOC and showed an overlap with the
      normal lung tissue. The fractional blood volume V (B) was relatively low for both
      tracers, not exceeding 0.3. The highest significant logarithmic correlation was
      found for the FD of the two tracers (r=0.764, p=0.017). The logarithmic
      correlation for SUVs was also significant (r=0.646, p=0.060), as was that forV
      (B) (r=0.629, p=0.069). In contrast, none of the eight metastases which were
      positive on FDG PET showed any DOTATOC uptake. CONCLUSION: The results
      demonstrated moderate (68)Ga-DOTATOC uptake in primary NSCLC but did not provide
      any evidence for SSTR2 expression in metastases. This may be caused by loss of
      the gene expression in metastases as compared with the primary tumours.

PMID- 16570186
TI  - Estimation of cardiac output in a pharmacological trial using a simple method
      based on arterial blood pressure signal waveform: a comparison with pulmonary
      thermodilution and echocardiographic methods.
AB  - OBJECTIVE: Cardiac output (CO) has traditionally been measured using invasive
      techniques, which involve an element of risk. Thus, a reliable less-invasive
      method for determining CO would be very valuable for research use. We tested
      whether simple analysis of the arterial pulse waveform, not requiring large
      vessel catheterisation or expensive equipment, could provide an estimate of CO
      that is accurate enough for pharmacological studies. METHODS: We measured CO in
      11 healthy male subjects who received low and high doses of dexmedetomidine
      (alpha2-adrenoceptor agonist), using pulse contour analysis, echocardiography and
      pulmonary thermodilution techniques. RESULTS: At baseline, these methods gave the
      following mean (SD) values of CO: 6.18 (1.59), 5.22 (1.35) and 7.03 (1.54) l/min,
      respectively. High-dose dexmedetomidine reduced CO to 4.50 (0.68), 3.65 (0.65)
      and 4.80 (0.89) l/min, corresponding to -25 (14) %, -28 (12) % and -30 (14) %
      reductions from baseline, respectively. The pulse contour method described these
      dexmedetomidine-induced changes in CO very similarly to the thermodilution and
      echocardiographic methods. The limits of agreement [bias (2SD)] were 0.55 (2.55)
      and -0.10 (2.04) l/min, respectively. CONCLUSION: The minimally invasive pulse
      contour analysis technique might be suitable for pharmacological studies for the
      detection of major drug-induced reductions in CO.

PMID- 16570187
TI  - The influence of various genotypes on the metabolic activity of NAT2 in a Chinese
      population.
AB  - AIM: To determine the phenotype and genotype of NAT2 in a Chinese population and
      study the influence of various NAT2 genotypes on the NAT2 activity. METHODS: A
      reverse dot blot method was used to detect the genotype of NAT2 in 120 healthy
      Chinese subjects. All subjects were given a single dose of 500 mg sulphadimidine
      (SM(2)). The plasma concentration of SM(2) and acetyl-SM(2) (AcSM(2)) 6 h after
      administration was determined. Molar metabolic ratio (MR) was calculated by the
      ratio of AcSM(2) to AcSM(2)+SM(2). RESULTS: Totals of 53 (44.2%), 47 (39.2%) and
      20 (16.7%) subjects were homozygotes for wild type (wt/wt), heterozygotes for
      mutant (m/wt) and homozygotes for mutant (m/m), respectively. The MR of 120
      subjects was 0.714+/-0.237. Twenty subjects (16.7%) were classified as poor
      metabolizers. All subjects in the m/m group were poor metabolizers. The MRs of
      the wt/wt, m/wt and m/m groups were 0.886+/-0.060, 0.719+/-0.089 and 0.246+/
      0.105 (P<0.001), respectively. There was a significant difference between
      different NAT2 m/wt genotypes (P<0.001) and m/m genotypes (P<0.001). MR
      correlated well with NAT2 genotypes (r=0.947). CONCLUSION: Various NAT2 genotypes
      have a significant impact on the metabolic activity of NAT2 in Chinese people.

PMID- 16570188
TI  - Pharmacokinetics of piperaquine after repeated oral administration of the
      antimalarial combination CV8 in 12 healthy male subjects.
AB  - OBJECTIVE: To investigate the pharmacokinetic properties of piperaquine after
      repeated oral administration of the antimalarial combination CV8 in healthy
      subjects. METHODS: Twelve healthy fasted Vietnamese males were administered four
      tablets CV8 (320 mg piperaquine phosphate, 32 mg dihydroartemisinin, 5 mg
      primaquine phosphate, 90 mg trimethoprim) on day 1, followed by two tablets every
      24th hour, for a total of 3 days. Blood samples were frequently drawn on days 1
      and 3 and sparsely drawn until day 29. Samples were analyzed for piperaquine
      using solid phase extraction followed by high-performance liquid chromatography.
      Population pharmacokinetic parameter estimates were obtained by nonlinear mixed
      effects modeling of the observed data using NONMEM. RESULTS: A two-compartment
      disposition model with an absorption lag time described the observed piperaquine
      concentrations. Absorption profiles were found to be irregular with double or
      multiple peaks. A dual pathway first-order absorption model improved the goodness
      of fit. Piperaquine pharmacokinetics were characterized by a large volume of
      distribution and a terminal half-life of several days. Estimates [95% confidence
      interval (CI)] of CL/F, V(ss)/F and t(1/2)(z) were found to be 56.4 (29-84) l/h,
      6,000 (3,500-8,500) l and 11.7 (8.3-15.7) days, respectively. CONCLUSION:
      Piperaquine pharmacokinetics after repeated oral doses were characterized by
      multiple concentration peaks and multiphasic disposition, resulting in a long
      terminal half-life. Sustained exposure to the drug after treatment should be
      taken into account when designing future clinical studies, e.g. duration of
      follow-up, and may also drive resistance development in areas of high malaria
      transmission.

PMID- 16570190
TI  - Identification of Alu elements mediating a partial PMP22 deletion.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is most
      frequently caused by deletion of a 1.4-Mb region in chromosome 17p11.2-12
      including the peripheral myelin protein 22 (PMP22) gene. Smaller deletions
      partially affecting the PMP22 gene are less frequently observed. We identified in
      a HNPP patient a deletion of the 5' region of PMP22 including non-coding exon 1,
      coding exons 2 and 3, whereas, exons 4 and 5 were present. PMP22 exon 3- and 4
      specific qPCR resulted in a deletion of one exon 3 allele but in the presence of
      2 exon 4 alleles. SNP analysis revealed the presence of heterozygosity for PMP22
      coding exons 4 and 5. Finally, MLPA specific for the CMT1A region defined this
      deletion for the entire 5' region of PMP22 (exons 1, 2 and 3). These partial HNPP
      deletions may be missed by other techniques, e.g., STR marker analysis. Alu
      elements have been reported to mediate non-allelic recombination events.
      Bioinformatic analysis revealed 12 Alu elements flanking in close neighbourhood
      the estimated 40-kb deletion region as candidates for recombination events. PCR
      primers were designed to identify a breakpoint-spanning product including the
      respective Alu elements. PCR-driven identification of a junction fragment was
      successful with AluJo-AluSq and AluYb9-AluSq specific primer pairs comprising the
      same intronic region of PMP22. Sequence analysis of these breakpoint-overlapping
      PCR fragments revealed a 29-bp motif including a chi-like sequence (GCTGG)
      present both in the AluYb9 and the AluSq element. These data confirm that low
      copy repeats (LCRs) mediate non-allelic homologous recombinations (NAHR).

PMID- 16570191
TI  - Novel mutations in CLN8 in Italian variant late infantile neuronal ceroid
      lipofuscinosis: Another genetic hit in the Mediterranean.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are autosomal recessive neurodegenerative
      disorders typically characterized by the accumulation of autofluorescent material
      in tissues. On the basis of clinical features, age at onset, and molecular
      genetic defects, it is possible to distinguish at least nine forms. The CLN8 form
      was first described in Finland, where all the patients are homozygous for a
      p.Arg24Gly mutation in CLN8. More recently, it has been found that a subset of a
      Turkish variant of late infantile NCL (v-LINCL) is also associated with CLN8
      mutations. To identify the molecular defect in Italian patients with v-LINCL, the
      CLN8 gene was directly sequenced in 10 patients. Controls were screened by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis. Five fluorescent-labeled microsatellite markers covering 1 cM around
      the gene were used for haplotype analysis. In three Italian v-LINCL patients,
      identified in a small area in southern Italy, we detected four new mutations in
      CLN8: c.66delG (p.Gly22fs), c.88G>C (p.Ala30Pro), c.473A>G (p.Tyr158Cys), and
      c.581A>G (p.Gln194Arg). The single-base deletion was found in two unrelated
      patients. The novel missense mutations were not identified in ethnically matched
      control chromosomes. Our findings expand the number of CLN8 variants and
      corroborate the notion that CLN8 patients are not confined to the Finnish
      population.

PMID- 16570192
TI  - Adult intussusception due to cocaine-induced bowel wall hematoma: a case study.
AB  - The authors present a patient in whom colocolic intussusception occurred as a
      result of bowel wall ischemia and hematoma. Imaging features and pathogenesis of
      bowel ischemia and intussusception will be briefly discussed, as well as its
      relationship to cocaine abuse. The importance of recognizing complications of
      cocaine abuse in today's emergency department patient population will be
      emphasized.

PMID- 16570189
TI  - From early homologue recognition to synaptonemal complex formation.
AB  - This review focuses on various aspects of chromosome homology searching and their
      relationship to meiotic and vegetative pairing and to the silencing of unpaired
      copies of genes. Chromosome recognition and pairing is a prominent characteristic
      of meiosis; however, for some organisms, this association (complete or partial)
      is also a normal part of nuclear organization. The multiple mechanisms suggested
      to contribute to homologous pairing are analyzed. Recognition of DNA/DNA homology
      also plays an important role in detecting DNA segments that are present in
      inappropriate number of copies before and during meiosis. In this context, the
      mechanisms of methylation induced premeiotically, repeat-induced point mutation,
      meiotic silencing by unpaired DNA, and meiotic sex chromosome inactivation will
      be discussed. Homologue juxtaposition during meiotic prophase can be divided into
      three mechanistically distinct steps, namely, recognition, presynaptic alignment,
      and synapsis by the synaptonemal complex (SC). In most organisms, these three
      steps are distinguished by their dependence on DNA double-strand breaks (DSBs).
      The coupling of SC initiation to (and downstream effects of) DSB formation and
      the exceptions to this dependency are discussed. Finally, this review addresses
      the specific factors that appear to promote chromosome movement at various stages
      of meiotic prophase, most particularly at the bouquet stage, and on their
      significance for homologue pairing and/or achieving a final pachytene
      configuration.

PMID- 16570193
TI  - ACL reconstruction: patellar tendon versus hamstring grafts--economical aspects.
AB  - The aim of the present investigation was to compare the costs for the use of
      patellar tendon versus hamstring tendons as grafts for anterior cruciate ligament
      (ACL) reconstruction including the different fixation methods. The background is
      that during recent years there has been a dramatic shift from patellar tendon to
      hamstring tendons in ACL reconstructions in Sweden. All our patients with ACL
      reconstructions performed during 1 year (2004) were included. Knee joints
      numbering 440 in 439 patients were primary ACL reconstructions. A hamstring graft
      was used in 345 knee joints (78.4%) and a patellar tendon graft in 95 (21.6%) of
      the patients (Table 2). On average 34 (SD 12.9; range 14-63) ACL reconstructions
      per surgeon were performed by a total of 14 surgeons. The average cost for
      patellar tendon procedure was 197 euros compared to 436 euros for the hamstring
      procedure. Mean time for surgery in primary reconstructions was 11.5 min shorter
      (P<0.001) for patellar tendon reconstructions (71.3+/-31 min) compared to
      hamstring reconstructions (83.2+/-27 min). This means a difference in cost of 90
      euros. The total additional cost (fixation and surgery time) for the hamstring
      method compared to the patellar tendon method was on an average 329 euros. From a
      strict economic point of view we therefore recommend or at least consider the use
      of the patellar tendon as a graft in ACL reconstructions.

PMID- 16570194
TI  - Nerve sheath ganglion of the tibial nerve presenting as a Baker's cyst: a case
      report.
AB  - Nerve sheath ganglion is a relatively rare clinical entity commonly found in the
      peroneal nerve in the lower limb or the ulnar nerve in the upper extremity. It is
      rarely found in the tibial nerve. The occurrence of a nerve sheath ganglion in a
      patient's tibial nerve has been identified. The initial presentation of the tumor
      mass has been very similar to that of a Baker's cyst, namely a soft undulating
      popliteal mass. Yet, the case also presented symptoms and signs of tibial nerve
      compressive neuropathy. We present here a rare case of nerve sheath ganglion of
      the tibial nerve. Clinical courses of the patient were reviewed, and relevant
      issues were discussed with a thorough literature review.

PMID- 16570195
TI  - Assessment of the influence of operative factors in the success of endoscopic
      third ventriculostomy in children.
AB  - OBJECTIVE: To determine if operative factors correlate with success of endoscopic
      third ventriculostomy (ETV) in the treatment of hydrocephalus. MATERIALS AND
      METHODS: The ETV procedure video of 33 hydrocephalic children was reviewed. Mean
      age at operation was 76 months (range: 1-196). Success was defined as no need for
      shunt in the long term. We calculated the relative size of stoma as the
      percentage of stoma diameter to the distance between posterior clinoid-basilar
      artery. Factors analysed were: intra-operative haemorrhage, stoma size,
      thick/double third ventricular floor, pre-pontine adhesions presence, brisk
      cerebro-spinal fluid (CSF) flow through the stoma as well as hydrocephalus cause,
      previous shunt presence, CSF infection or haemorrhage and previous ETV. Analysis
      was performed using chi-square, linear regression, and one-way ANOVA. RESULTS:
      Overall ETV success rate was 42%. Mean stoma size was 37%. For the entire group,
      none of the operative factors correlated statistically with success. Previous
      shunt presence adversely correlated with success (p=0.008). The highest success
      rate was in the aqueduct stenosis group. In patients without previous shunt
      (n=17), stoma size over 30% tended towards significance (p=0.094), CSF leak was
      adversely associated with ETV success (p=0.041) and mean stoma size was 41.3% in
      successful ETV and 27.8% in unsuccessful ETV (p=0.072). In patients with previous
      shunt (n=16), thin third ventricular floor was a negative predisposing factor
      (p=0.057). CONCLUSION: This study did not demonstrate a correlation between the
      presence of pre-pontine adhesions, double or thickened floor of third ventricle
      and ETV success. In patients without previous shunt, stoma size may correlate
      with success. CSF leak was strongly associated with failure.

PMID- 16570196
TI  - Metachronous secondary atypical meningioma and anaplastic astrocytoma after
      postoperative craniospinal irradiation for medulloblastoma.
AB  - INTRODUCTION: Malignant brain tumors have been reported to occur after childhood
      irradiation more frequently than in the nonirradiated population. DISCUSSION: In
      this study, we report the case of a 15-year-old boy treated for medulloblastoma
      with surgery and craniospinal radiotherapy, who developed a meningioma 18 years
      after initial treatment and subsequently an anaplastic astrocytoma 23 years after
      primary treatment. The meningioma was resected without complications. The patient
      is currently alive but with recurrent astrocytoma after a complete remission on
      temozolomide monotherapy. Second malignancies are a rare, potentially devastating
      risk in cancer survivors, with risk continuing lifelong.

PMID- 16570197
TI  - Pediatric cerebellar pleomorphic xanthoastrocytoma with anaplastic features: a
      case of long-term survival after multimodality therapy.
AB  - CASE REPORT: A 4-year-old girl had a large midline cerebellar solid and cystic
      mass partially attached to the meninges. The original diagnosis was glioblastoma
      multiforme and she was treated by a gross-total surgical resection followed by
      chemotherapy and radiation therapy to the posterior fossa during the ensuing 14
      months. She has received no further therapy and appears to be doing well 12 years
      later. This unusual favorable clinical outcome prompted our review of this case.
      METHODS: Additional special stains and immunocytochemistry were performed on the
      paraffin embedded tumor sections. RESULTS: We have confirmed the original
      histopathological observations of hypercellularity and focal nuclear
      pleomorphism, atypical mitoses, vascular hyperplasia, as well as focal necrosis.
      However, the additional stains revealed that the tumor is a relatively well
      circumscribed meningeal-based astrocytic tumor (positive for GFAP) with extensive
      reticulin deposit and focal neuronal differentiation (positive for
      synaptophysin). A Ki67 labeling index is generally very low, but is positive in
      up to 5-10% of tumor cells focally. In the light of the favorable clinical
      outcome and the overall histological features, this tumor may be best
      reclassified as a rare example of cerebellar pleomorphic xanthoastrocytoma with
      foci of anaplasia.

PMID- 16570200
TI  - Genome-wide linkage analysis of population variation in high-density lipoprotein
      cholesterol.
AB  - Lower plasma levels of high-density lipoprotein cholesterol (HDL-C) are
      associated with the metabolic syndrome (insulin resistance, obesity,
      hypertension) and higher cardiovascular risk. Recent association studies have
      suggested rare alleles responsible for very low HDL-C levels. However, for
      individual cardiovascular risk factors, the majority of population-attributable
      deaths are associated with average rather than extreme levels. Therefore, genetic
      factors that determine the population variation of HDL-C are particularly
      relevant. We undertook genome-wide and fine mapping to identify linkage to HDL-C
      in healthy adult nuclear families from the Victorian Family Heart Study. In 274
      adult sibling pairs (average age 24 years, average plasma HDL-C 1.4 mmol/l),
      genome-wide mapping revealed suggestive evidence for linkage on chromosome 4 (Z
      score = 3.5, 170 cM) and nominal evidence for linkage on chromosomes 1 (Z = 2.1,
      176 cM) and 6 (Z = 2.6, 29 cM). Using genotypes and phenotypes from 932 subjects
      (233 of the sibling pairs and their parents), finer mapping of the locus on
      chromosome 4 strengthened our findings with a peak probability (Z score = 3.9) at
      169 cM. Our linkage data suggest that chromosome 4q32.3 is linked with normal
      population variation in HDL-C. This region coincides with previous reports of
      linkage to apolipoprotein AII (a major component of HDL) and encompasses the gene
      encoding the carboxypeptidase E, relevant to the metabolic syndrome and HDL-C.
      These findings are relevant for further understanding of the genetic determinants
      of cardiovascular risk at a population level.

PMID- 16570199
TI  - Detection of parasitemia profiles by blood culture after treatment of human
      chronic Trypanosoma cruzi infection.
AB  - The change in parasitemia profile, measured by sequential blood cultures of 27
      benznidazole (Bz) treated patients compared with 13 untreated patients, on the
      chronic phase of chagas disease, is described. All patients were adults (age
      limits: 23-88) with positive serology (three tests); 23 of them were females. All
      patients were submitted to six blood cultures, three before and three after Bz
      treatment. The parasitemia was classified as nondetected (with three negative
      blood cultures), medium (one positive culture in three), and high (two or three
      positive cultures). From the eight patients with nondetected parasitemia before
      Bz, seven still had the same profile and only one switched to medium; from eight
      with medium parasitemia, seven shifted to nondetected, and one to high
      parasitemia. From the 11 patients with high parasitemia before Bz, ten converted
      to nondetected and only one was positive after Bz. Nineteen of the 27 patients
      changed the parasitemia profile (70.4%), and the rate of therapeutic failure was
      11.1% (3/27) during the first 24 months of follow-up after Bz. The shift to
      nondetected parasitemia profile was from 8/27 to 24/27 patients after Bz
      treatment for the first 2 years. Only 46.2% (6/13) of the nontreated individuals
      changed the parasitemia profile. We conclude that there is a strong trypanocide
      effect of Bz (88.8%) and a rate of therapeutic failure of 11.1% during the first
      2 years after trypanocidal treatment.

PMID- 16570201
TI  - Membranous nephropathy in Schimke immuno-osseous dysplasia.
AB  - Schimke immuno-osseous dysplasia is a rare autosomal recessive multi-system
      disorder, with clinical features of growth retardation, spondylo-epiphyseal
      dysplasia, nephrotic syndrome and immunodeficiency beginning in childhood. Here,
      we report a new case, in a 10-year-old boy with characteristic symptoms of
      Schimke immuno-osseous dysplasia. The patient presented with short stature and,
      later, developed nephrotic syndrome and peritonitis. In addition, he had
      perinuclear anti-neutrophilic cytoplasmic antibody (p-ANCA)-positive arthritis.
      Renal pathology of the patients with this disease usually show focal segmental
      glomerulonephritis, whereas our patient had membranous nephropathy, which has not
      previously been reported.

PMID- 16570202
TI  - Renal amyloidosis in a child with sickle cell anemia.
AB  - The kidney is frequently affected in patients with sickle cell syndrome, i.e.,
      homozygous and heterozygous patients, with a consequently large spectrum of renal
      abnormalities that may range from minimal functional changes to chronic renal
      failure. Here, we present a 13-year-old boy with sickle cell anemia (SCA) (HbSS)
      who was referred to our unit with nephrotic syndrome. Renal biopsy revealed AA
      type amyloidosis on the basis of light microscopic findings, indicating Congo red
      staining and immunohistochemistry. He had neither a family history of familial
      Mediterranean fever (FMF) nor any complaint of recurrent abdominal pain,
      arthritis, and fever, but frequent painful vaso-occlusive crises. The patient was
      found to have no MEFV gene (Mediterranean feVer) mutations either. Painful
      episodic attacks might provoke recurrent acute inflammation, leading to repeated
      stimulation of acute phase responses and cause secondary amyloidosis. To our
      knowledge, this boy is the first case of SCA complicated by renal amyloidosis
      observed in childhood.

PMID- 16570204
TI  - Effect of supine knee position on obstructive sleep apnea.
AB  - We previously reported a case of a middle-aged man whose obstructive sleep apnea
      (OSA) was virtually eliminated when he slept in the supine "knees up" position.
      In this study, we attempt to replicate this phenomenon in a group of volunteers
      with previously diagnosed OSA. Results indicated no significant improvement in
      OSA when sleeping supine knees up. Examination of distribution of within
      subjects' change [calculated as Respiratory Disturbance Index (RDI) in the "knees
      down" position vs RDI in the knees up position] indicated a trend for improvement
      in the latter (p=0.12, two-tailed probability). These results suggest that knee
      position is unlikely to be a robust intervention for OSA though they allow for
      the possibility that some patients may have a moderation of their condition by
      such a manipulation.

PMID- 16570205
TI  - The art of surgery in the 21st century: based on natural sciences and new ethical
      dimensions.
AB  - BACKGROUND AND AIMS: In the future, new surgical techniques will only be
      introduced in clinical practice if evidence-based results--frequently the results
      of controlled clinical trials--are presented. Unlike any other medical
      discipline, surgeons provide their diagnostic and operative skills through the
      surgeons' hand and the use of technical equipment, which ranges from instruments
      and devices employed during operation to the use of surgical robots. RESULTS:
      Analysing the fundaments of surgery on the turn of the century, there is only a
      little doubt about the increasing impact of data deriving from natural sciences
      on knowledge in medicine and management of diseases. The natural scientific
      method of detecting, measuring, and verifying facts is the methodological basis
      of surgery as well. The autonomy of the surgeon's clinical decision making is
      significantly restricted by the definition of guidelines. They shift the decision
      from a single patient to a collective panel. Patient safety and the efficiency of
      new treatment modalities compared with previous standards are the criteria for
      the judgement of innovative surgery today. The communication and interaction
      between surgeon-scientist and patients is guaranteed legally by written
      consensus. But beside of the high probability of benefit from therapy and written
      consensus, the surgeon-patient relation is determined by these factors:
      limitation of time for care of an individual patient, increase of time for
      administration and documentation, increase of bureaucratic barriers for medical
      research, and health cost constraints. CONCLUSION: The medical mandate to cure a
      sick patient is an individual mandate to take action. Measures, numbers, and
      images are only preconditions for a surgeon's action in daily clinical work; they
      can never replace it. The call for an ethical imperative in scientific surgery
      that is dependent on technology is justified when the state of science and
      uncritical use of surgical skills and financial constraints have major impact on
      providing medical care.

PMID- 16570203
TI  - Short-term outcomes of severe lupus nephritis in a cohort of predominantly
      African-American children.
AB  - Renal involvement is one of the major determinants of the outcome in patients
      with systemic lupus erythematosus. Although African-American ethnicity has been
      suggested to be a poor prognostic factor in severe lupus nephritis in adult
      patients, information on outcomes of African-American children with this disease
      is still very limited. We retrospectively studied the patients diagnosed with
      severe lupus nephritis by renal biopsy at Le Bonheur Children's Medical Center
      from January 1990 to December 2003. All patients were below the age of 18 years
      at the time of biopsy. Clinical features assessed included age, gender, race,
      estimated glomerular filtration rate (GFR), presence of hypertension, gross
      hematuria, degree of proteinuria, complement 3 and 4 levels, serum albumin, renal
      histology and dose of oral prednisone. Forty-four patients were studied: 82% were
      African-American and 89% were female. Mean age at biopsy was 14.2+/-3 years
      (median 15.0 years; range 4.7 years to 17.0 years). Renal biopsies were assessed
      according to the WHO classification. Twenty-seven percent, 43%, and 30% were in
      class III, IV and V, respectively. At presentation, 55% had hypertension and 23%
      had a history of macroscopic hematuria. The patients had varying degrees of
      proteinuria, including 18% with nephrotic syndrome. Eighteen percent had moderate
      renal insufficiency with estimated GFRs less than 50 ml/1.73 m2 body surface area
      per minute. All the patients were treated with corticosteroids. Sixty-eight
      percent also received cyclophosphamide and 20% received either mycophenolate
      mofetil (MMF) or azathioprine (AZA). Two patients developed end stage renal
      disease and required chronic dialysis within 12 months of biopsy. At the 12-month
      follow-up visit, 23% of patients had complete remission and 48% had partial
      remission. The mean estimated GFR had increased from 96.0 ml/1.73 m2 per minute
      to 124 ml/1.73 m2 per minute (P=0.03). Mean serum creatinine levels decreased
      from 1.62 mg/dl to 0.91 mg/dl (P=0.03). Complement 3 levels increased from 54.3
      mg/dl to 90.3 mg/dl (P<0.01). Mean serum albumin levels also increased from 2.8
      mg/dl to 3.6 mg/dl (P<0.01) and urine protein-to-creatinine ratio decreased from
      5.8 to 1.0 (P<0.01). The average prednisone dose decreased from 0.96 mg/kg per
      day to 0.41 mg/kg per day (P=0.64). In our center, with predominantly African
      American children, patients with lupus nephritis presented similarly to those in
      other studies with predominantly Caucasian patients, and short-term renal
      outcomes were not different.

PMID- 16570206
TI  - The rubella virus nonstructural protease recognizes itself via an internal
      sequence present upstream of the cleavage site for trans-activity.
AB  - The substrate requirement for rubella virus protease trans-activity is unknown.
      Here, we analyzed the cleavability of RV P200-derived substrates varying in their
      N-terminal lengths (72-475 amino acids) from the cleavage site by the RV protease
      trans-activity. Only substrates with at least 309 amino acid residues N-terminal
      to the cleavage site were able to undergo cleavage. Further, rubella sequence was
      found to be necessary in the N-terminal region of the substrate, whereas a
      heterologous sequence C-terminal to the cleavage site was tolerated. These
      results demonstrated a requirement for residues located between amino acids 994
      1102 of the RV P200 polyprotein, besides its cleavage site for RV protease trans
      activity. This region overlaps with the starting site of the essential cis
      protease activity of RV P200 polyprotein. This is a novel observation for a viral
      protease of the family Togaviridae.

PMID- 16570207
TI  - Effect of culture conditions and mother's age on the sensitivity of Daphnia magna
      Straus 1820 (Cladocera) neonates to hexavalent chromium.
AB  - Daphnia magna is a freshwater cladoceran used worldwide as test organism in
      aquatic toxicity assays. In Mexico there is a test protocol for this species;
      nevertheless, some aspects of the controlled neonate production, as well as the
      possible consequences of the reproducers' culture conditions on the response of
      neonates to the toxic substance, are not completely known. In the present study,
      we evaluated the effect of temperature and photoperiod on the acute toxicity of
      CrVI in D. magna neonates, aimed at providing useful information on the Median
      Lethal Concentration (LC50) to this heavy metal, which is used as reference
      toxicant in some laboratories. D. magna was cultured at 20 and 25 degrees C, in
      combination with two photoperiod values: 16:8 and 12:12 (light:dark) during 40
      days; the green microalga Ankistrodesmus falcatus (4x10(5) cells ml(-1)) was
      supplied as food. Once the reproduction began, the neonates were removed and
      acute toxicity bioassays at 20 and 25 degrees C were performed, by exposing them
      to hexavalent chromium. We also determined changes in neonates' size at 20 and 25
      degrees C. Chromium toxicity increased along with increasing temperatures, and
      LC50 values were slightly lower for the first and last clutches in the observed
      period, but these findings are not conclusive because of the large variability
      recorded. The average LC50's were 0.2076+/-0.0164 mg l(-1) (at 20 degrees C) and
      0.1544+/-0.0175 mg l(-1) (at 25 degrees C). The reproducers' culture temperature
      had no effect on neonates' sensitivity to chromium, in spite of performing the
      tests at temperatures either lower or higher than those at which the neonates had
      been obtained. The length of neonates produced during the first two clutches
      (<1.25 mm) was significantly lower than that measured in neonates of following
      reproductions (>1.3 mm), and were smaller at 25 degrees C; however, this did not
      seem to affect their sensitivity to chromium.

PMID- 16570208
TI  - Abamectin effects on rainbow trout (Oncorhynchus mykiss).
AB  - The effect of abamectin (ABM) on rainbow trout (Oncorhynchus mykiss) was studied.
      The acute toxicity of ABM on rainbow trout was established, following the target
      58-h water bath exposure of ABM concentrations from 0.6 to 4.5 microg/l, on the
      basis of which LD75 (4.0 microg/l) was calculated. The histological changes in
      organs showed a direct toxicity of ABM for rainbow trout since degenerative
      changes in brain and kidney and--to a minor extent--in liver were established.
      The values of the ABM residues in fish muscle tissue with skin were proportional
      to the exposed concentrations of ABM.

PMID- 16570209
TI  - Cellular localisation of adenylyl cyclase: a post-genome perspective.
AB  - The intracellular messenger cAMP is essential for vital processes ranging from
      ovulation to cognition. There are 10 genes for adenylyl cyclase (AC), the
      biosynthetic enzyme of cAMP. Nine of these encode membrane-bound proteins and one
      gives rise to soluble AC. The understanding of the biological significance of
      this molecular diversity is incomplete. Membrane-bound ACs conform to the same
      structural blueprint but have markedly different regulatory characteristics. AC
      mRNAs are differentially distributed in the body suggesting non-redundant
      physiological functions. The subcellular localisation of AC isoforms has not been
      examined in detail. Here we discuss the current knowledge on the intracellular
      targeting of AC isoforms, and highlight the technical problems of AC detection,
      some of which appear to be caused by the poor quality-control of commercially
      supplied antibodies. The principal message is that intracellular targeting of ACs
      may be isoform-specific and also dependent on the cellular context of expression.

PMID- 16570210
TI  - Serotonin-synthesizing neurons in the rostral medullary raphe/parapyramidal
      region transneuronally labelled after injection of pseudorabies virus into the
      rat tail.
AB  - Serotonin-synthesizing raphe/parapyramidal neurons (5-HT neurons) may function as
      sympathetic premotor neurons regulating sympathetic outflow to the cutaneous
      vascular bed. In the present study a genetically engineered pseudorabies virus
      (PRV) expressing green fluorescent protein (GFP) was injected into the rat tail.
      After survival for 3-4 days the medulla oblongata was examined using double-label
      immunohistochemistry, with an antibody against GFP for the virus and an antibody
      against phenylalanine hydroxylase 8 (PH8) for 5-HT synthesis. Sections were
      examined using light microscopy, and conventional and confocal fluorescence
      microscopy. There were two subpopulations of PRV+ve neurons in the
      raphe/parapyramidal region: a more dorsally and laterally located subgroup of
      medium-sized and large neurons, mainly non-serotonergic, and a more ventrally
      located subgroup of small mainly serotonin-synthesizing neurons, including those
      just dorsal to the pyramids, those in raphe pallidus, and those in close
      relationship to the ventral surface in the parapyramidal-subependymal zone.

PMID- 16570212
TI  - The distribution and neurochemistry of the parathyroid hormone 2 receptor in the
      rat hypothalamus.
AB  - This study reports the distribution of parathyroid hormone 2 receptor (PTH2R)
      immunoreactive fibers in the hypothalamus using fluorescent amplification
      immunocytochemistry. The pattern of immunolabeling is strikingly similar to that
      of tuberoinfundibular peptide of 39 residues (TIP39), a peptide recently purified
      from bovine hypothalamus and proposed to be a ligand of the PTH2R based on
      pharmacological data. To investigate the anatomical basis of suggestions that
      TIP39 affects the secretion of several hypophysiotropic hormones we performed
      double-labeling studies and found that only somatostatin fibers contain PTH2R in
      the median eminence, which suggests that somatostatin release could be directly
      regulated via the PTH2R. However, several hypothalamic nuclei projecting to the
      median eminence contain a high density of both TIP39 and PTH2R fibers and
      terminals. We report here, that the PTH2R terminals also contain vesicular
      glutamate transporter-2, and suggest that TIP39 terminals are ideally positioned
      to modulate glutamatergic influences on hypophysiotropic neurons.

PMID- 16570211
TI  - Effect of lesion of a5 and a7 brainstem noradrenergic areas or transection of
      brainstem pathways on sympathoadrenal activity in rats during immobilization
      stress.
AB  - Both A5 and A7 brainstem noradrenergic cell groups innervate dorsal horns of the
      spinal cord. Moreover, A5 cell group directly innervates sympathetic
      preganglionic neurons. Thus, A5 and A7 noradrenergic neurons could modulate the
      sympathoadrenal system (SAS) activity. We investigated the role of A5 and A7
      noradrenergic cell groups in regulation of the SAS activity under control and
      stressful conditions. We evaluated the effect of electrolytical lesions of A5 or
      A7 cell groups and also the effect of bilateral brainstem cuts interrupting
      brainstem pathways on tyrosine hydroxylase gene expression in A5 and A7 areas and
      on the SAS activity measured by plasma epinephrine and norepinephrine levels. We
      have found that immobilization stress increases activity of the A5 and A7
      brainstem areas and also levels of the gene expression of tyrosine hydroxylase,
      the rate-limiting catecholamine biosynthetic enzyme. Immobilization of sham
      operated and brainstem pathways transected or A5 or A7 lesioned animals induced a
      similar, highly significant increase in plasma epinephrine and norepinephrine
      levels in both sham-operated and A5 or A7 destroyed or transected groups. Our
      data suggest that both A5 and A7 noradrenergic cell groups are activated during
      immobilization stress. However, transection of brainstem pathways innervating A5
      and A7 neurons or lesion of A5 or A7 cell groups is not sufficient enough for
      changes in immobilization stress-induced activation of the SAS. We suggest that
      neither A5 and A7 noradrenergic neurons nor the transected brainstem pathways
      represent structures crucial for an activation of the SAS during immobilization
      stress. We hypothesize that during regulation of the stress response, various
      areas and pathways are involved and the elimination just one of them might be
      compensated by the remained intact areas and pathways.

PMID- 16570213
TI  - Gradients in the health status and developmental risks of young children: the
      combined influences of multiple social risk factors.
AB  - OBJECTIVES: To analyze child vulnerability as a profile of multiple risk factors
      for poorer health based on race/ethnicity, social class (maternal education and
      family poverty status), child health insurance coverage, and maternal mental
      health. Profiles are examined in relation to disparities in the health status and
      developmental risks of young children. DATA SOURCES: Cross-sectional data on
      2,068 children ages 4-35 months from the 2000 National Survey of Early Childhood
      Health. STUDY DESIGN: Multiple logistic regression models are used to examine
      risk profiles in relation to child health status and developmental risk (based on
      parent concerns about development). The profiles are also examined in relation to
      three measures of basic access to health care: telephone contact with a
      physician, well-child visit in the past year, and missed or delayed needed care.
      PRINCIPAL FINDINGS: About one-third of (or 3.1 million) young children in the
      United States have two or more risk factors (RF) for poor health. Controlling for
      other family factors, having more RFs is associated with poorer health status
      (i.e., percent reported "good/fair/poor" vs. "excellent/very good") and being
      higher risk for developmental delays. For example, the likelihood of having
      either poorer health or higher developmental risk increases with each RF (vs.
      zero): 1 RF (OR = 1.70, CI: 1.20-2.38), 2 RFs (OR = 3.28, CI: 2.27-4.73), 3 RFs
      (OR = 4.69, CI: 2.84-7.73), 4 RFs (OR = 14.58, CI: 4.98-42.64). Higher RFs were
      also associated with poorer health care access. CONCLUSIONS: This study
      demonstrates a dose-response relationship of higher risk profiles with poorer
      child health status and higher developmental risk. Because children with higher
      profiles of risk are also more likely to lack access to care, this suggests that
      children who most need care have the greatest difficulty obtaining it. Addressing
      health gradients for vulnerable children will require explicit attention to these
      multiple, overlapping risk factors.

PMID- 16570214
TI  - Adaptive and maladaptive behavior in children with Smith-Magenis Syndrome.
AB  - Children with Smith-Magenis Syndrome (SMS) exhibit deficits in adaptive behavior
      but systematic studies using objective measures are lacking. This descriptive
      study assessed adaptive functioning in 19 children with SMS using the Vineland
      Adaptive Behavior Scales (VABS). Maladaptive behavior was examined through parent
      questionnaires and the Childhood Autism Rating Scale. Cognitive functioning was
      evaluated with an age-appropriate test. Children scored below average on VABS
      Communication, Daily Living Skills, and Socialization scales. Learning problems
      and hyperactivity scales on the Conner's Parent Rating Scale were elevated, and
      girls were more impulsive than boys. Stereotypic and self-injurious behaviors
      were present in all children. Cognitive functioning was delayed and consistent
      with communication and daily living skills, while socialization scores were
      higher than IQ.

PMID- 16570215
TI  - Inhibition of CYP6B1-mediated detoxification of xanthotoxin by plant
      allelochemicals in the black swallowtail (Papilio polyxenes).
AB  - The structural and biosynthetic diversity of allelochemicals in plants is thought
      to arise from selection for additive toxicity as a consequence of toxin mixture
      or for enhanced toxicity as a result of synergism. In order to understand how
      insects cope with this type of plant defense, we tested the effects of some
      allelochemicals in host plants of the black swallowtail Papilio polyxenes on the
      xanthotoxin-metabolic activity of CYP6B1, the principal enzyme responsible for
      the detoxification of furanocoumarins in this caterpillar. Additionally, the
      effects of some synthetic compounds not normally encountered by P. polyxenes on
      CYP6B1 were tested. These studies demonstrate that the integrity of
      furanocoumarin structure is important for competitive binding to the active site
      of CYP6B1, even though the carbonyl group on the pyranone ring apparently does
      not affect its inhibitory capacity, as in the case of furanochromones. Angular
      furanocoumarins are generally less phototoxic to many organisms than linear
      furanocoumarins due to their reduced capacity for cross-linking DNA strands, yet
      they are more toxic than linear furanocoumarins to black swallowtail larvae. This
      enhanced toxicity in vivo may be due to the ability of angular furanocoumarins to
      bind to the active site of CYP6B1 without being rapidly metabolized. This binding
      reduces the availability of CYP6B1 to metabolize other linear furanocoumarins.
      The structure-activity relationships for methylenedioxyphenyl compounds,
      flavonoids, imidazole, and imidazole derivatives are also discussed in light of
      their capacity to inhibit the xanthotoxin-metabolic activity of CYP6B1.

PMID- 16570219
TI  - Assessment of new vehicles emissions certification standards in the metropolitan
      area of Mexico City.
AB  - Light duty gasoline vehicles account for most of CO hydrocarbons and NOx
      emissions at the Metropolitan Area of Mexico City (MAMC). In order to ameliorate
      air pollution from the beginning of 2001, Tier 1 emission standards became
      mandatory for all new model year sold in the country. Car manufacturers in Mexico
      do not guarantee the performance of their exhaust emissions systems for a given
      mileage. The purpose of this study was to assess whether the Tier 1 vehicles will
      stand the certification values for at least 162000 km with the regular fuel
      available at the MAMC. Mileage accumulation and deterioration show that certified
      carbon monoxide emissions will stand for the useful life of the vehicles but in
      the case of non-methane hydrocarbons will be shorter by 40%, and nitrogen oxides
      emissions above the standard will be reached at one third of the accumulated
      kilometers. The effect of gasoline sulfur content, on the current in use Tier 1
      vehicles of the MAMC and the impact on the emissions inventory in year 2010
      showed that 31000 extra tons of NOx could be added to the inventory caused by the
      failure of the vehicles to control this pollutant at the useful life of vehicles.

PMID- 16570218
TI  - Characterization of Escherichia coli isolates from different fecal sources by
      means of classification tree analysis of fatty acid methyl ester (FAME) profiles.
AB  - Microbial source tracking (MST) methods need to be rapid, inexpensive and
      accurate. Unfortunately, many MST methods provide a wealth of information that is
      difficult to interpret by the regulators who use this information to make
      decisions. This paper describes the use of classification tree analysis to
      interpret the results of a MST method based on fatty acid methyl ester (FAME)
      profiles of Escherichia coli isolates, and to present results in a format readily
      interpretable by water quality managers. Raw sewage E. coli isolates and animal
      E. coli isolates from cow, dog, gull, and horse were isolated and their FAME
      profiles collected. Correct classification rates determined with leaveone-out
      cross-validation resulted in an overall low correct classification rate of 61%. A
      higher overall correct classification rate of 85% was obtained when the animal
      isolates were pooled together and compared to the raw sewage isolates. Bootstrap
      aggregation or adaptive resampling and combining of the FAME profile data
      increased correct classification rates substantially. Other MST methods may be
      better suited to differentiate between different fecal sources but classification
      tree analysis has enabled us to distinguish raw sewage from animal E. coli
      isolates, which previously had not been possible with other multivariate methods
      such as principal component analysis and cluster analysis.

PMID- 16570217
TI  - Revisiting "Success": Posttrial analysis of a gender-specific HIV/STD prevention
      intervention.
AB  - Alongside the recognized need to foster the development of innovative gender
      specific HIV interventions, researchers face the urgent need to further
      understand how current interventions do or do not work. Few studies build
      posttrial qualitative analysis into standardized interview assessments in
      randomized controlled trials in order to bolster an assessment of how
      interventions work. The current investigation is a posttrial qualitative analysis
      carried out on a randomly selected subsample (N = 180), representing 50% of women
      who participated in a 3-arm randomized controlled trial known as Project FIO (The
      Future Is Ours). FIO was a gender-specific HIV prevention intervention carried
      out with heterosexually active women in a high seroprevalence area of New York
      City. Posttrial qualitative results extend an understanding of the success of the
      trial (e.g., reductions in unsafe sex). Qualitative results reflect how the
      Modified AIDS Risk Reduction Model operated in the expected direction across
      experimental groups. Results also highlight women's empowerment narratives,
      reflecting the salience of bodily and sexual rights aspects of the intervention.

PMID- 16570220
TI  - Multiscale spatial and small-scale temporal variation in the composition of
      Riverine fish communities.
AB  - We studied the multiscale (sites, river reaches and rivers) and short-term
      temporal (monthly) variability in a freshwater fish assemblage. We found that
      small-scale spatial variation and short-term temporal variability significantly
      influenced fish community structure in the Macquarie and Namoi Rivers. However,
      larger scale spatial differences between rivers were the largest source of
      variation in the data. The interaction between temporal change and spatial
      variation in fish community structure, whilst statistically significant, was
      smaller than the variation between rivers. This suggests that although the fish
      communities within each river changed between sampling occasions, the underlying
      differences between rivers were maintained. In contrast, the strongest
      interaction between temporal and spatial effects occurred at the smallest spatial
      scale, at the level of individual sites. This means whilst the composition of the
      fish assemblage at a given site may fluctuate, the magnitude of these changes is
      unlikely to affect larger scale differences between reaches within rivers or
      between rivers. These results suggest that sampling at any time within a single
      season will be sufficient to show spatial differences that occur over large
      spatial scales, such as comparisons between rivers or between biogeographical
      regions.

PMID- 16570221
TI  - Comparative metal distribution in hair of Pakistani and Libyan population and
      source identification by multivariate analysis.
AB  - Using nitric acid-perchloric acid wet digestion based FAAS method ten selected
      metals (Cd, Co, Cr, Fe, K, Mn, Na, Ni, Pb and Zn) were determined in the scalp
      hair of male Pakistani and Libyan donors (n = 62), between 3-54 years age and
      residing in typical urban areas. The study was taken up to identify sources of
      metal distribution in two diverse population segments exposed to different
      environments. Sodium emerged with the highest mean hair concentration of 511.0
      microg/g and 496.9 mug/g for Libyan and Pakistani donors respectively, followed
      by K, at 266.2 microg/g and 242.4 microg/g for the two donor categories. Cadmium
      showed the lowest mean hair concentration for both Pakistani (0.380 microg/g) and
      Libyan (0.530 microg/g) donors. Levels of Na, K, Pb, Cr and Cd were higher in
      hair of Libyan donors compared with Pakistani counterparts which showed higher
      comparative levels of Zn, Fe, Co, Ni and Mn. Strong metal-to-metal correlations
      were found between Na-K (r = 0.638) and Cd-Co (r = 0.574) for Pakistani donors,
      while for Libyan donors, Na-K (r = 0.680) and Fe-Mn (r = 0.624) correlations
      emerged as strongly significant. Only K was found to have a strong positive
      correlation (r = 0.611) with age for Pakistani donors while this correlation was
      significantly negative (r = -0.500) for Libyan donors, probably arising from
      individual food habits. Other metals showed no viable relationship with age.
      Principal Component Analysis (PCA) and Cluster Analysis (CA) of the data
      evidenced food, industrial emissions and automobile emissions as possible sources
      of metal distribution. The results of the present study are compared with those
      reported for subjects from other regions of the world.

PMID- 16570222
TI  - Assessing respiratory morbidity through pollution status and meteorological
      conditions for Delhi.
AB  - The study focuses on assessing the status of respiratory morbidity in Delhi over
      a four years period from 2000-2003. An attempt was made to investigate the role
      of important pollutants (SO(2), NO(2), SPM and RSPM) and various meteorological
      factors (temperature minimum & maximum, relative humidity at 0830 and 1730 hrs.
      and wind speed) in being responsible for respiratory admissions on account of
      COPD, asthma and emphysema. The study showed that winter months had greater
      exposure risk as pollutants often get trapped in the lower layers of atmosphere
      resulting in high concentrations. Statistical analysis revealed that two
      pollutants have significant positive correlation with the number of COPD cases
      viz., SPM (r = 0.474; p < 0.01) and RSPM (r = 0.353; p < 0.05), while a
      meteorological factor temperature (minimum) has a significant negative
      correlation (r = -0.318; p < 0.05) with COPD. Stepwise multiple regression
      analysis was performed for COPD as dependent variable and R(2) value of 0.33 was
      obtained indicating that SPM and RH(1730) were able to explain 33 percent
      variability in COPD. The partial correlation of SPM and RH(1730) on COPD was
      higher than any other combination and therefore they can be regarded as important
      contributing variables on COPD.

PMID- 16570223
TI  - Monitoring urbanization of Iskenderun, Turkey, and its negative implications.
AB  - This study aimed to analyze long-term urban land use (LU) change and its negative
      implications on the coastal environment of Iskenderun, Turkey. Information on
      urban LU change for the 144-year period between 1858 and 2002 was extracted from
      a historic city plan, black-white monoscopic aerial photographs, and Landsat ETM+
      imagery. According to the results, areal extent of urban areas has increased
      approximately 40 times during the past 144 years. The population growth as a
      result of industrial developments and permanent migration was main driving force
      to the urbanization. Environmental problems that resulted from rapid development
      in the region such as air, water and soil pollution were highlighted and some
      recommendations were made in the light of qualitative and quantitative
      information on the urbanization and its negative consequences.

PMID- 16570224
TI  - Hydrochemical changes over time in the Zahedan Aquifer, Iran.
AB  - Groundwater in the Zahedan Aquifer located in the arid southeast of Iran was
      chemically characterized to understand both the nature of the alluvium aquifer
      and the effect of human activities, specifically sewage disposal on groundwater
      quality. Concentrations of major cations and anions in the Zahedan Aquifer are
      much higher than concentrations observed in groundwater of similar settings.
      Although the nature of the aquifer and climatic parameters have affected the
      chemistry of groundwater, human impacts on the groundwater quality are more
      significant. The electrical conductivity in some areas of the Zahedan aquifer
      increased up to 7,500 microS/cm in 25 years. Human influences in some areas are
      so prevalent, that the groundwater type changed from a Na(+)-HCO(3) (-) in 1976
      to a Na(+)-Cl(-) type in 2000. The impact of human influences on the groundwater
      quality is also indicated through observed nitrate concentration up to 4.81 meq/L
      in the urban area.

PMID- 16570226
TI  - Temperature measurement and stratification in facultative waste stabilisation
      ponds in the UK climate.
AB  - Temperature measurements were taken at three pilot-scale facultative ponds
      located at Esholt wastewater treatment works in West Yorkshire, UK over two one
      year periods. The measurements were taken at different depths using a technology
      called Thermochron iButton. The iButton readings were compared with temperature
      measurements taken by a YSI sonde probe and maximum/minimum thermometers: they
      were found to be within 1 .C. In the temperature range 3.18 .C the mean weekly
      and monthly air temperatures were found to be good predictors for the mean weekly
      and monthly pond water-column temperatures. The level of stratification in the
      ponds under UK climatic conditions was assessed; the data revealed that the ponds
      remained thermally stratified for significant periods during the year despite
      their shallow depth.

PMID- 16570225
TI  - The influence of the biometric parameters on metallothionein and metal level in
      the heat-treated cytosol of the whole soft tissue of transplanted mussels.
AB  - The influence of the biometric parameters (shell mass, whole soft tissue mass,
      condition index) on MT and metal levels in the heat-treated cytosol of the whole
      soft tissue of transplanted mussels was studied over the period of one year. The
      positive correlation of three metals (Cd, Fe, Zn) with the shell mass indicated
      to time-dependent increase of their contents. Strong correlation of Mn content
      with the whole soft tissue mass (r = 0.74, p < 0.0001), and almost identical
      changes of these two parameters over the year make Mn a good indicator of
      mussel's condition. As opposed to the other metals, Cu content does not exhibit
      connection with biometry. On the other hand, MTs are highly influenced by
      biometry. As much as 65% of their variability could be explained by the changes
      of the shell mass and the whole soft tissue mass. Consequently, it is difficult
      to distinguish if the obtained positive correlation between Cd and MTs (r = 0.48,
      p < 0.05) reflects MT induction by Cd, or Cd accumulation as a result of age
      dependent increase of MTs. Due to the strong influence of the biometry on MT
      level, the whole soft tissue is not considered as the best choice for measuring
      MTs as a biomarker. Better option would be to isolate a specific tissue that
      shows indisputable connection between MT induction and metal accumulation.

PMID- 16570227
TI  - Aquifer transmissivity and basement structure determination using resistivity
      sounding at Jos Plateau State Nigeria.
AB  - A geoelectric investigation involving twenty-six vertical electrical soundings
      was carried out at Jos, Plateau State, North Central Nigeria. The survey was
      aimed at determining the structure of the underlying bedrock, as well as
      computing the transmissivity for the aquifer in the area. The basement
      geometrymapproduced from the results of the survey indicates that the bedrock is
      undulating lying at depths between 30 m to 6.5 m. There is evidence of faulting
      and fracturing within the area. Computation of aquifer transmissivity values
      based on the results obtained made it possible to demarcate regions with good
      ground water potential in the area.

PMID- 16570229
TI  - The role of indigenous bacterial and fungal soil populations in the
      biodegradation of crude oil in a desert soil.
AB  - The biodegradation capacity of indigenous microbial populations was examined in a
      desert soil contaminated with crude oil. To evaluate biodegradation, soil samples
      supplemented with 5, 10 or 20% (w/w) of crude oil were incubated for 90 days at
      30 degrees C. The effect of augmentation of the soil with vermiculite (50% v/v)
      as a bulking agent providing increased surface/volume ratio and improved soil
      aeration was also tested. Maximal biodegradation (91%) was obtained in soil
      containing the highest concentration of crude oil (20%) and supplemented with
      vermiculite; only 74% of the oil was degraded in samples containing the same
      level of crude oil but lacking vermiculite. Gas chromatograms of distilled
      fractions of crude oil extracted from the soil before and after incubation
      demonstrated that most of the light and part of the intermediate weight fractions
      initially present in the oil extracts could not be detected after incubation.
      Monitoring of microbial population densities revealed an initial decline in
      bacterial viable counts after exposure to oil, presumably as a result of the
      crude oil's toxicity. This decline was followed by a steep recovery in microbial
      population density, then by a moderate increase that persisted until the end of
      incubation. By contrast, the inhibitory effect of crude oil on the fungal
      population was minimal. Furthermore, the overall increased growth response of the
      fungal population, at all three levels of contamination, was about one order of
      magnitude higher than that of the bacterial population.

PMID- 16570228
TI  - Dynamics of reductive TCE dechlorination in two distinct H(2) supply scenarios
      and at various temperatures.
AB  - Anaerobic microbial dechlorination of trichloroethene (TCE) by a mixed,
      Dehalococcoides containing culture was investigated at different temperatures (4
      60 degrees C) using propionate and lactate as a slow- and fast-releasing hydrogen
      (H(2)) source, respectively. Distinct temperature-dependent dynamics of substrate
      fermentation and H(2) levels could explain observed patterns of dechlorination.
      While varying the temperature caused changes in rate, the overall pattern of
      dechlorination was characteristic of the supplied electron donor. Feeding
      cultures with a rapidly fermentable substrate such as lactate generally resulted
      in high H(2) concentrations and fast and complete dechlorination accompanied by
      rapid methanogenesis. In contrast, low H(2) release rates resulting from
      fermentation of propionate were associated with 2 to 3-fold longer time frames
      necessary for complete dechlorination at intermediate temperatures (15-30 degrees
      C). A lag-phase prior to dechlorination of cis-dichloroethene (cDCE), together
      with a characteristic build-up of H(2) and methane, was consistently observed at
      slow H(2) supply. At temperatures of 10 degrees C and lower, the system remained
      in this lag phase and no dechlorination past cDCE was observed within the
      experimental time frame. However, when lactate was the substrate, complete
      dechlorination of TCE occurred within 74 days at 10 degrees C, accompanied by
      methane production. The choice of fermentable substrate decisively influenced the
      rate and degree of dechlorination at an electron donor/TCE ratio as high as
      666:1. Temperature-dependent H(2) levels resulting from fermentation of different
      substrates could be satisfactorily explained through thermodynamic calculations
      of the Gibbs free energy yield assuming a constant metabolic energy threshold of 
      20 kJ/(mol reaction).

PMID- 16570230
TI  - Biodegradation of hexazinone by two isolated bacterial strains (WFX-1 and WFX-2).
AB  - Two hexazinone-degrading bacterial strains were isolated from soil by enrichment
      culture technique, and identified as Pseudomonas sp. and Enterobacter cloacap,
      respectively. The two purified isolates, designated as WFX-1 and WFX-2, could
      rapidly degrade hexazinone with half-lives of 3.08 and 2.95 days in mineral salts
      medium (hereafter referred to as MSM). In contrast, their mixed bacterial culture
      (herein abbreviated as MBC) was found to degrade hexazinone, at an initial
      concentration of 50 mg l(-1), by enhancing 2.3-fold over that when the isolates
      were used alone. The degradation of hexazinone by MBC in MSM clearly decreased
      concomitant with the increase of initial concentration, and the level of
      hexazinone that was toxic enough to totally inhibit degradation was in the range
      of 150-200 mg l(-1). The appropriately combined conditions for hexazinone
      degradation by MBC in MSM were studied, and found to be pH 5.5, 30 degrees C and
      at agitation of 120 rpm. The addition of MBC to soil had a greater impact on
      disappearance of hexazinone, which nearly increased fivefold over that of the
      control set. As a result, findings in the present investigation provide useful
      information for soil and water decontamination of hexazinone.

PMID- 16570232
TI  - Adrenocortical carcinoma -- improving patient care by establishing new
      structures.
AB  - BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly malignant tumour
      with a poor prognosis. Patients present with signs of steroid hormone excess
      (e.g., Cushing's syndrome) or symptoms due to an abdominal mass. DIAGNOSIS: In
      case of an adrenal mass, hormonal workup before surgery is required for
      differential diagnosis, perioperative management, and for follow-up. The imaging
      of choice is CT or MRI with MRI being of additional use when invasion of big
      vessels is suspected. Apart from that, the use of 18-FDG-PET is becoming
      increasingly established. TREATMENT: Surgical resection is the therapeutic option
      of choice in stages 1 - 3. In stage 4, the adrenolytic compound mitotane is part
      of the first-line treatment, but often needs to be combined with cytotoxic
      chemotherapy. Most patients will eventually have a recurrence, so adjuvant
      treatment (mitotane/tumour bed radiation) has to be considered in high risk
      patients, even if randomized controlled trials on adjuvant treatment are still
      lacking. STRUCTURAL PROGRESS: Several national and European structures have
      recently been established in order to increase our knowledge of ACC, improve
      therapeutic options and diagnostic procedures, and promote research. GANIMED, as
      a Germany-wide network of experts on adrenal diseases, has been founded allowing
      for improved gathering of data and joint studies. ENSAT (European Network for the
      Study of Adrenal Tumours) has been brought to life, aiming at European standards
      for therapy, diagnosis and tumour banking. Since 2003, patients can be enrolled
      in the German ACC Registry. France and Italy have also developed a central
      registry to collect nationwide data from patients with ACC. For the first time,
      patients with metastatic/unresectable ACC can participate in a prospective
      controlled randomized trial comparing two different cytotoxic chemotherapy
      regimes (FIRM-ACT).

PMID- 16570231
TI  - Immunohistochemical analysis of human skeletal muscle AMP deaminase deficiency.
      Evidence of a correlation between the muscle HPRG content and the level of the
      residual AMP deaminase activity.
AB  - We have previously described that, in healthy human skeletal muscle, an anti
      histidine-proline-rich-glycoprotein (HPRG) antibody selectively binds to type IIB
      fibers that are well known to contain the highest level of AMP deaminase (AMPD)
      activity, suggesting an association of the HPRG-like protein to the enzyme
      isoform M. The present paper reports an immunohistochemical study performed on
      human skeletal muscle biopsies from patients with AMPD deficiency and carried out
      utilizing both the anti-HPRG antibody and an anti-AMPD antibody specific for the
      isoform M. A correlation between the muscle content of the HPRG-like protein and
      the level of AMPD activity was demonstrated. In the specimens from patients with
      Acquired AMPD deficiency the HPRG-immunoreactivity was less intense than that
      shown by the control subjects and was related to the residual AMPD activity. The
      patients affected by Primary and Coincidental AMPD deficiency, which were
      characterized by an absence of enzyme activity and AMPD immunoreactivity, showed
      the lowest HPRG immunoreactivity that was clearly detectable by Western blot
      analysis, but not by immunohistochemistry. The interpretation of the significance
      of these observations suggests a physiological mutual dependence between skeletal
      muscle HPRG and AMPD polypeptides with regard to their stability.

PMID- 16570234
TI  - Visceral adipose tissue as an indicator of insulin resistance in nonobese
      patients with new onset type 2 diabetes mellitus.
AB  - BACKGROUND: Obesity and type 2 diabetes mellitus are characterized by insulin
      resistance. We determined the relationship between insulin resistance and
      visceral adipose tissue (VAT) and their correlation with bioimpedance analysis in
      nonobese new onset type 2 diabetes patients. METHODS: A number of 30 new onset
      type 2 diabetes patients and 20 healthy control subjects with similar features,
      age between 45 - 72 years old, BMI < 27 kg/m (2), C-peptide > 0.6 nmol/L, were
      included in study. Fasting blood glucose, HbA1c, serum lipids, BMI, insulin, C
      peptide, HOMA-IR, bioimpedance analysis and visceral and subcutaneous adipose
      tissue (by computed tomography) were measured. RESULTS: In the patient group, VAT
      was significantly higher compared to healthy control group (33.17 +/- 10.23 % vs.
      16.53 +/- 7.85 %, p < 0.001). In the patient group VAT was correlated with HOMA
      IR (r = 0.62, p = 0.003), but no significant correlation was observed between VAT
      and bioimpedance analysis. CONCLUSIONS: The amount of VAT is significantly higher
      in nonobese new onset patients with type 2 diabetes than the healthy control
      group. In these patients, VAT measured by CT is an important indicator of insulin
      resistance. Although bioimpedance analysis can give an idea about total body fat
      and obesity, it is not sufficient in evaluating fat distribution and therefore is
      not effective in predicting insulin resistance.

PMID- 16570233
TI  - Relationship between peripheral diabetic neuropathy and microvascular reactivity
      in patients with type 1 and type 2 diabetes mellitus -- neuropathy and
      microcirculation in diabetes.
AB  - The aim of the study was to evaluate differences in the relationship between
      peripheral diabetic neuropathy and microvascular reactivity in type 1 and type 2
      diabetic patients. Twenty-eight type 1 and 37 type 2 diabetic patients were
      included in the study. Control groups consisted of 18 and 25, age and body mass
      index matched healthy persons. The presence of peripheral neuropathy was
      estimated by vibration perception threshold higher than 20 V evaluated by
      biothesiometry. Microvascular reactivity was examined by laser doppler fluxmetry
      using postocclusive reactive hyperemia and thermal hyperemia. The following
      variables of vascular reactivity were examined: peak flow after occlusion as a
      difference between maximal and basal perfusion (PORH (max)), mean velocity
      increase during postocclusive hyperemia (PORH (max)/t (1)), peak flow during
      thermal hyperemia (TH (max)) and the mean velocity increase in the perfusion
      during thermal hyperemia (TH (max)/t (2)). These parameters are expressed in
      perfusion units (PU) or in perfusion units per second (PU . s (-1)). The
      microvascular reactivity in type 1 diabetic patients without evidence of
      peripheral neuropathy was comparable with that in healthy persons and it was
      significantly higher than in type 1 diabetic patients with peripheral neuropathy
      in all tested parameters (PORH (max): 64 [40; 81] PU vs. 24 [17; 40] PU, p <
      0.001, PORH (max)/t (1): 5.41 [2.69; 8.18] PU/s vs. 1.21 [0.69; 2.5] PU/s, p <
      0.001, TH (max): 105 [77; 156] PU vs. 56 [46; 85] PU, p < 0.001 and TH (max)/t
      (2): 2.48 [1.67; 3.33] PU/s vs. 0.87 [0.73; 1.06] PU/s, p < 0.001). On the
      contrary, no difference in the microvascular reactivity parameters was found
      between type 2 diabetic patients with and without neuropathy (PORH (max): 48 [30;
      60] PU vs. 49 [36; 57] PU, NS, PORH (max)/t (1): 3.46 [2.15; 5.19] PU/s vs. 3.29
      [2.45; 4.8] PU/s, NS, TH (max): 95 [78; 156] PU vs. 97 [73; 127] PU, NS and TH
      (max)/t (2): 1.45 [0.95; 2.84] PU/s vs. 1.37 [1.12; 1.95] PU/s, NS). In both
      these groups microvascular reactivity was comparable with that estimated in the
      age and BMI matched healthy persons. An inverse relationship was observed between
      microvascular reactivity and vibratory perception threshold in type 1 diabetic
      patients, but it was not true in type 2 diabetic patients. We suppose that the
      pathogenesis of neuropathy and impaired microvascular reactivity may be
      differently influenced by metabolic factors in type 1 and type 2 diabetic
      patients.

PMID- 16570235
TI  - Results of a randomised controlled cross-over trial on the effect of continuous
      subcutaneous glucose monitoring (CGMS) on glycaemic control in children and
      adolescents with type 1 diabetes.
AB  - OBJECTIVE: To study the feasibility and the influence on glycaemic control of
      continuous glucose monitoring (CGMS) in young patients with type 1 diabetes.
      DESIGN AND METHODS: A double-blinded, cross-over study was performed in 30
      children (median age 11.1 years [range: 2.3 - 16.3], diabetes duration 2.1 years
      [0.2 - 7.1]). Patients were randomised into an open (A) or blind study arm (B).
      Both groups performed standardised self-monitoring blood glucose (SMBG) and
      received CGMS at the beginning of the study, at 3 and 6 months, each. In the
      blinded arm, patients and investigator were concealed from CGMS data. After 3
      months, open and blinded study arms crossed over. Average glucose values and area
      under the glucose curve (AUC) per 24 h, above 180 and below 60 mg/dl were
      calculated from CGMS. Haemoglobin A1c (HbA1c) was measured at each study point.
      RESULTS: Despite comparable clinical characteristics between the 15 patients of
      each arm, mean HbA1c was slightly lower in arm A than in B at baseline (7.8 +/-
      1.2 % vs. 8.4 +/- 1.1 %, p = 0.148), at 3 months (7.8 +/- 1.1 % vs. 8.3 +/- 1.1
      %, p = 0.233), and significantly lower at 6 months (7.6 +/- 1.1 % vs. 8.5 +/- 0.9
      %, p = 0.026). However, no significant change of HbA1c occurred within each arm
      (A, p = 0.183 and B, p = 0.823), irrespectively whether CGMS data were blinded or
      not. Likewise, mean glucose and hyper- or hypoglycaemia values did not change
      significantly. CONCLUSIONS: In this setting, CGMS did not decisively influence
      glycaemic control of a total study cohort. More frequent use of CGMS at shorter
      intervals in single patients with hyper- or hypoglycaemic problems may be of
      greater value than SMBG.

PMID- 16570236
TI  - Continuous glucose monitoring -- a novel approach to the determination of the
      glycaemic index of foods (DEGIF 1) -- determination of the glycaemic index of
      foods by means of the CGMS.
AB  - The glycaemic index (GI) is a measure of the food power to raise plasma glucose
      (PG) concentration after a meal. For its determination, classical methods
      register the development of glucose concentration in capillary plasma or whole
      blood. The aim of this prospective open-label trial was to compare the GI of
      selected foods obtained by means of the Continuous Glucose Monitoring System
      (CGMS) (Minimed Medtronic, Northridge, USA) which has not been applied for this
      purpose until now, with the respective GI determined by a conventional method
      using the Glucometer Advance System (GAS) (Hypoguard, Woodbridge, United
      Kingdom), and to assess the advantages of each approach. METHODS: Portions of
      tested foods containing 50 g of carbohydrates were eaten for breakfast and for
      dinner after 10 and 4 h fast, respectively, by 20 healthy volunteers. Using GAS,
      PG-curves were constructed from 9 PG values at time 0, 15, 30, 45, 60, 75, 90,
      105 and 120 min after the meal, and, using CGMS, from 25 values of interstitial
      fluid glucose concentration (ISFG) stored within 120 min in 5-minute intervals in
      CGMS memory. The GI was calculated (for GAS and CGMS separately) by dividing the
      incremental area under the curve for the tested food by the average area of 3
      tests performed with the standard. Having excluded tests with missing glucose
      values, there remained 285 GAS- and 290 CGMS tests for further analysis. In each
      volunteer, each food was tested 3 times within one week so that 1 to 3 GI's were
      obtained and averaged. The GI for each tested food was calculated as the mean
      from the respective average GI's of 20 volunteers. The GI-variability was
      assessed according to the respective SD. The preference of GAS vs. CGMS in the
      persons tested was explored by means of a questionnaire. MS Excel and the
      statistical program SPSS v. 10.1 were used to analyze the data. RESULTS: The GI
      values (mean +/- SD) measured by GAS/CGMS were for dark chocolate 43.6 +/- 22.13
      %/44.0 +/- 21.71 % (p > 0.01); for apple baby food 46.1 +/- 21.38 %/53.8 +/-
      37.69 % (p > 0.01); for puffed rice squares 76.5 +/- 20.24 %/76.9 +/- 27.62 % (p
      > 0.01); for yogurt 43.2 +/- 20.17 %/37.7 +/- 21.55 % (p > 0.01). The GI's of
      dark chocolate, apple baby food and yogurt, determined by either method, were
      significantly lower than the GI of puffed rice squares (p < 0.01). CGMS was
      preferred by 12 of 20 volunteers (60 %). CONCLUSIONS: No significant difference
      could be seen between the GI's determined by conventional method (GAS) and by
      CGMS (p > 0.01). The method with CGMS is reliable and comfortable for both tested
      persons and investigators. Hence, it appears to become a sophisticated approach
      to determine the GI.

PMID- 16570237
TI  - Cardiovascular risk management by blocking the endocannabinoid system.
AB  - The specific blockade of endocannabinoids at the level of the cannabinoid
      receptor 1 (CB (1) receptor) is a new therapeutic option to reduce body weight
      and manage cardiovascular risk. Although clinical trials are underway to document
      the safety and efficacy of this approach, much is still unknown about this
      endogenous system. Endocannabinoids and their receptors are expressed in the
      central nervous system as well as in the periphery and regulate the central
      neural circuits for food uptake and peripheral metabolic circuits. Within the
      context of food uptake, the stimulation of the CB (1) receptor with Delta (9)
      tetrahydrocannabinol (Delta (9)-THC) enhances food consumption, while its
      blockade with receptor antagonists is an emerging relevant therapeutic means to
      reduce body weight. Rimonabant is the first of a new class of drugs that
      interferes with the endocannabinoid system by blocking the CB (1) receptor. In
      recent clinical studies, a substantial reduction in body weight and waist
      circumference was associated with an improvement of the cardiovascular risk
      profile. In particular, increased HDL cholesterol, decreased serum triglycerides
      and improved insulin sensitivity were observed. Further research will serve to
      establish the role of these compounds in cardiovascular risk management.

PMID- 16570238
TI  - Effects of long-term treatment with resveratrol and subcutaneous and oral
      estradiol administration on the pituitary-thyroid-axis.
AB  - The lack of estrogen during menopause is associated with various symptoms
      including osteoporosis, cardiovascular diseases, and menopausal symptoms. For
      many years, conventional hormone replacement therapy has been successfully used
      to treat these conditions. However, in light of recent studies that draw
      attention to potential hazards of conventional HRT, various attempts were
      undertaken to search for alternatives of classical HRT. Phytoestrogens are
      supposed to ameliorate various discomforts associated with menopause. Resveratrol
      (RES) is present in red wine, grapes and peanuts and has been implicated in
      cardioprotection and prevention of adverse side effects observed after regular
      HRT. As the pituitary-thyroid axis is a target of estrogen action, we first
      assessed the effects of E2 administration on thyroid hormone stimulating hormone
      releasing hormone (TRH)-induced thyroid stimulating hormone (TSH) secretion from
      pituitary cell cultures in vitro. Our data reveal that E2 treatment augments the
      TRH-induced TSH secretion. We furthermore designed a long-term study of three
      months to assess the effects of subcutaneous and oral administration of 17beta
      estradiol (E2), as well as the actions of RES on the pituitary-thyroid axis in
      ovariectomized (OVX) female rats. Our results demonstrate that serum levels of
      1.0 and 8.1 microM RES lead to a significant increase in total serum
      triiodthyronine (T3) levels. OVX induces TSHbeta mRNA in the adenohypohysis and
      E2 treatment attenuates this effect. Treatment of rats with subcutaneous implants
      of E2 does not affect the pituitary-thyroid axis, whereas orally applied E2
      benzoate (E2B) increases plasma TSH and total thyroxine (T4) in OVX rats. In all
      animals, we could not detect changes in thyroid morphology as assessed by
      hematoxylin-eosin (HE) and Perjod-Acid Schiff's (PAS) staining.

PMID- 16570239
TI  - Prenatal diagnosis of Fukuyama congenital muscular dystrophy.
AB  - Fukuyama congenital muscular dystrophy (FCMD) is characterized by infantile
      hypotonia, symmetrical generalized muscle weakness, and neuronal migration
      disturbances that result in changes consistent with cobblestone lissencephaly
      with cerebral and cerebellar cortical dysplasia. FCMD is recognized as an
      autosomal recessive genetic defect. Genetic counselling is recommended for
      parents at risk of having a child with FCMD. Given the high risk and overwhelming
      prospect of having another child with this incurable devastating condition leads
      many couples to consider prenatal diagnosis. In Japanese families, haplotype
      analysis using microsatellite markers is available. In non-Japanese families, DNA
      sequence analysis is available. Both disease-causing alleles of an affected
      family member must be identified before prenatal testing can be performed.

PMID- 16570240
TI  - Rapid genetic analysis of oculocutaneous albinism (OCA1) using denaturing high
      performance liquid chromatography (DHPLC) system.
AB  - OBJECTIVES: To present the prenatal genetic diagnoses and counseling for two
      cases of oculocutaneous albinism (OCA) type I family by detection of mutations in
      the OCA1 gene by denaturing high performance liquid chromatography (DHPLC) system
      and a review of the literature. METHODS: All DNA samples were extracted from
      peripheral whole blood and amniocentesis-derived cells. Mutation analysis was
      performed for all five coding exons of the TYR gene, which were amplified by PCR.
      DHPLC was used for heteroduplex detection and sequence analysis was performed to
      demonstrate the mutation loci. RESULTS: Case 1: After sampling of blood from the
      family members and performing amniocentesis of the fetus, it was demonstrated
      that the affected boy and the female fetus were shown to be compound
      heterozygotes for mutations in the TYR gene. In addition, it was shown that the
      parents were carriers of the two mutations. However, the couple chose to keep the
      baby. Case 2: Mutation analysis of the DNA of the siblings revealed two
      heterozygous mutations in the TYR gene. Her husband is free of the disease.
      According to the principles of autosomal recessive inheritance, the incidence of
      affected offspring is very low. CONCLUSIONS: Herein we introduce a novel
      application for molecular diagnostic of DHPLC coupled with direct sequencing,
      which can provide an effective and exact diagnosis in patients with albinism.
      Clinicians should be cognizant of the risk of OCA inheritance by the offspring
      through careful identification of genetic mutations and the inheritance mode,
      both important to ensure comprehensive genetic counseling.

PMID- 16570241
TI  - Pharmacologic transgene control systems for gene therapy.
AB  - Pharmacologic transgene-expression dosing is considered essential for future gene
      therapy scenarios. Genetic interventions require precise transcription or
      translation fine-tuning of therapeutic transgenes to enable their titration into
      the therapeutic window, to adapt them to daily changing dosing regimes of the
      patient, to integrate them seamlessly into the patient's transcriptome orchestra,
      and to terminate their expression after successful therapy. In recent years,
      decisive progress has been achieved in designing high-precision trigger-inducible
      mammalian transgene control modalities responsive to clinically licensed and
      inert heterologous molecules or to endogenous physiologic signals. Availability
      of a portfolio of compatible transcription control systems has enabled assembly
      of higher-order control circuitries providing simultaneous or independent control
      of several transgenes and the design of (semi-)synthetic gene networks, which
      emulate digital expression switches, regulatory transcription cascades,
      epigenetic expression imprinting, and cellular transcription memories. This
      review provides an overview of cutting-edge developments in transgene control
      systems, of the design of synthetic gene networks, and of the delivery of such
      systems for the prototype treatment of prominent human disease phenotypes.

PMID- 16570243
TI  - Tendon and neurovascular bundle displacement in the palm with hand flexion and
      extension: an MRI and gross anatomy correlative study.
AB  - This study evaluated the correlative use of MRI methods and gross anatomy to
      monitor tendon displacement in the central region of the palm at rest and during
      flexion and extension of the metacarpophalangeal and interphalangeal joints with
      respect to the corresponding neurovascular bundles (NVBs). In all of the samples
      the neutral and extended positions showed the NVB to be palmar with respect to
      the flexor tendons, while during flexion tendon displacement caused the NVB to be
      dorsal to both the flexor digitorum superficialis (FDS) and flexor digitorum
      profundus (FDP) tendons. T1-weighted MR images correlated with gross anatomical
      slides demonstrated that significant changes occur in the relative positions of
      the flexor tendons and associated NVBs of the palm upon flexion and extension.

PMID- 16570242
TI  - Anti-tumor efficacy of a transcriptional replication-competent adenovirus, Ad-OC
      E1a, for osteosarcoma pulmonary metastasis.
AB  - BACKGROUND: Osteosarcoma (OSA) is the most frequent type of primary malignant
      bone tumor and is apt to occur in children and young adults. Pulmonary metastasis
      (OSPM) is the major reason for its fatal outcome. Osteocalcin (OC) is a major
      noncollagenous bone protein whose expression is limited almost exclusively to
      bone marrow and osteotropic tumors. OC is also known to express in cell lines
      with bone metastasis feathers. Gene therapy strategies with the OC promoter
      directing the replication of adenovirus in a tumor-specific manner are a
      potential modality for OSPM therapy. METHODS: We detected OC mRNA expression by
      RNA in situ hybridization in OSA and OSPM samples from patients, and tested OC
      promoter transcriptional activity in OSA and non-OSA cell lines. Then we used a
      transcriptional replication-competent adenovirus, Ad-OC-E1a, to treat OSPM, and
      evaluated its tumor-specific replication and killing activities in vitro as well
      as anti-OSPM efficacy in vivo via systemic delivery. RESULTS: OC mRNA was
      detected in all types of OSA tissues, including OSPM tissues. The transcriptional
      activity of the OC promoter was much higher in a OSPM cell line SAOS-2LM7 and
      primary OSA cell line MG63 than in non-OSA cell lines, including cell lines from
      breast cancer, colon cancer, and liver cancer. Ad-OC-E1a expressed E1a protein
      only in MG63 and SAOS-2LM7, which indicated that adenovirus E1a was under strict
      control by the OC promoter. Ad-OC-E1a demonstrated killing and viral replication
      activity close to wild-type adenovirus levels in MG63 and SAOS-2LM7, but the
      killing and viral replication activities were attenuated significantly in cells
      expressing low OC transcriptional activity. To test whether Ad-OC-E1a could be
      used to target human OSPM in vivo, SAOS-2LM7 pulmonary metastasis models in nude
      mice were induced and treated by tail-vein injection with Ad-OC-E1a. Compared to
      tumor nodules in the lung in groups treated with PBS or control virus, the
      quantity of metastasized tumor nodules decreased significantly. Adenovirus
      infected cells were stained immunohistochemically only inside and around the OSPM
      nodules but spared normal lung tissue and other organs. CONCLUSIONS: These data
      demonstrated that OC promoter could direct adenovirus replication by controlling
      the E1a gene to target human OSPM in a tumor-specific manner, providing an
      efficient tool to develop a feasible therapeutic modality for OSPM.

PMID- 16570244
TI  - Accelerating MR elastography: a multiecho phase-contrast gradient-echo sequence.
AB  - PURPOSE: To demonstrate the feasibility of using a multiecho phase-contrast (PC)
      gradient-echo sequence with motion-sensitizing gradient (MSG) to accelerate MR
      elastography (MRE) acquisitions in comparison to single-echo PC sequences.
      MATERIALS AND METHODS: The sequence was implemented and compared with a
      conventional single-echo sequence as the standard of reference in both agarose
      phantoms and in vivo in the biceps of three healthy volunteers. For
      reconstruction of the elasticity modulus, a local frequency estimation (LFE)
      algorithm was used. ETL factors of 1-16 were evaluated. RESULTS: Phantom
      experiments demonstrated excellent consistency between single-echo and multiecho
      measurements in terms of wave equivalency, SNR, and reconstructed shear modulus.
      Additionally, the in vivo MRE examinations showed an excellent correspondence to
      the single-echo results. Minor loss of wave amplitude was observed at higher ETL
      factors. CONCLUSION: The results demonstrate that a multiecho sequence is
      suitable for accelerating MRE in nearly homogeneous tissue, such as muscle. It
      provides equivalent elasticity values in a significantly reduced scan time
      compared to a single-echo sequence. The maximum achievable ETL factor must be
      individually determined for the target tissue.

PMID- 16570247
TI  - Dynein mediates retrograde neurofilament transport within axons and anterograde
      delivery of NFs from perikarya into axons: regulation by multiple phosphorylation
      events.
AB  - We examined the respective roles of dynein and kinesin in axonal transport of
      neurofilaments (NFs). Differentiated NB2a/d1 cells were transfected with green
      fluorescent protein-NF-M (GFP-M) and dynein function was inhibited by co
      transfection with a construct expressing myc-tagged dynamitin, or by
      intracellular delivery of purified dynamitin and two antibodies against dynein's
      cargo domain. Monitoring of the bulk distribution of GFP signal within axonal
      neurites, recovery of GFP signal within photobleached regions, and real-time
      monitoring of individual NFs/punctate structures each revealed that pertubation
      of dynein function inhibited retrograde transport and accelerated anterograde,
      confirming that dynein mediated retrograde axonal transport, while intracellular
      delivery of two anti-kinesin antibodies selectively inhibited NF anterograde
      transport. In addition, dynamitin overexpression inhibited the initial
      translocation of newly-expressed NFs out of perikarya and into neurites,
      indicating that dynein participated in the initial anterograde delivery of NFs
      into neurites. Delivery of NFs to the axon hillock inner plasma membrane surface,
      and their subsequent translocation into neurites, was also prevented by
      vinblastine-mediated inhibition of microtubule assembly. These data collectively
      suggest that some NFs enter axons as cargo of microtubues that are themselves
      undergoing transport into axons via dynein-mediated interactions with the actin
      cortex and/or larger microtubules. C-terminal NF phosphorylation regulates motor
      association, since anti-dynein selectively coprecipitated extensively
      phosphorylated NFs, while anti-kinesin selectively coprecipitated less
      phosphorylated NFs. In addition, however, the MAP kinase inhibitor PD98059 also
      inhibited transport of a constitutively-phosphorylated NF construct, indicating
      that one or more additional, non-NF phosphorylation events also regulated NF
      association with dynein or kinesin.

PMID- 16570245
TI  - Extended harmonic phase tracking of myocardial motion: improved coverage of
      myocardium and its effect on strain results.
AB  - PURPOSE: To extend the harmonic phase (HARP) tracking method in order to track
      the myocardial tissue that appears near the epicardial contour during systole and
      reappears near the endocardial contour during diastole, due to the longitudinal
      motion and conical shape of the heart. MATERIALS AND METHODS: A mathematical
      model of myocardial deformation was used to quantify the accuracy of the extended
      HARP tracking and of the strain computation. For six healthy volunteers, the
      number of tracked points and the two-dimensional strain components were computed
      with the extended and with the original HARP tracking version. RESULTS: High
      accuracy was obtained for the circumferential strain (maximum error is 0.5%
      relative to analytical strain). The extended version tracked 22 +/- 7%, 51 +/-
      19%, and 67 +/- 20% more points than the original version on the basal, mid, and
      apical slices, respectively (P < or = 0.001 for each slice), and yielded a
      decreased circumferential shortening (relative decrease: 2 +/- 4%, 9 +/- 4%, and
      12 +/- 5% for the three slices; P < 0.005 for mid and apex), at end systole.
      These differences in circumferential strain were related to the more complete
      coverage of the myocardial wall with tracked points. CONCLUSION: The extended
      HARP tracking also provides strain values from myocardial regions that were not
      covered by the original HARP tracking.

PMID- 16570248
TI  - Shaggy/GSK-3beta kinase localizes to the centrosome and to specialized
      cytoskeletal structures in Drosophila.
AB  - The assembly of a functional bipolar mitotic spindle requires an exquisite
      regulation of microtubule behavior in time and space. To characterize new
      elements of this machinery we carried out a GFP based "protein trap" screen and
      selected fusion proteins which localized to the spindle apparatus. By this method
      we identified Shaggy, the Drosophila homologue of glycogen synthase kinase-3beta
      (GSK-3beta), as a component of centrosomes. GSK-3beta acting in the Wingless
      signaling pathway is involved in a vast range of developmental processes, from
      pattern formation to cell-fate specification, and is a key factor for cell
      proliferation in most animals. We exploited our Shaggy::GFP Drosophila line to
      analyze the subcellular localizations of GSK-3beta/Shaggy and shed light on its
      multiple roles during embryogenesis. We found that Shaggy becomes enriched
      transiently in a variety of specialized cytoskeletal structures of the embryo,
      including centrosomes throughout mitosis, suggesting that this kinase is involved
      in the regulation of many aspects of the cytoskeleton function.

PMID- 16570250
TI  - The relationship between work permits, injury, and safety training among working
      teenagers.
AB  - BACKGROUND: No information exists on the differences between teenagers with work
      permits and teenagers without work permits in regards to workplace injury, near
      miss incidents, and safety training. METHODS: In May 2003, an anonymous
      questionnaire was administered to 7,506 teens attending high school throughout
      the five public health regions of Wisconsin. All students in the participating
      school districts were invited to respond. The questionnaire included questions
      about employment, injury, safety and health training, and school performance.
      RESULTS: Overall, 6,382 teens participated in the survey and 49% reported working
      during the school year. Seventy percent of all working teens reported having a
      permit. Females were more likely to have work permits compared with males (71%
      vs. 68%, P = 0.018). The percentages of teens with permits varied by job and
      ranged from 55% for teens working in tree-trimming/cutting to 85% for teens
      working in restaurants or fast food establishments. Teens with work permits were
      no less likely to be injured than those without permits (AOR = 1.07, 95% CI: 0.85
      1.33) and no less likely to have a near-miss incident (AOR = 1.28, 95% CI: 0.99
      1.63). However, teens with permits were significantly more likely to be given
      safety training than teens without permits (AOR = 2.61, 95% CI: 2.21-3.10).
      CONCLUSIONS: Although teens with work permits were more likely to report
      receiving safety training than teens without permits, the occurrence of injury
      was no different among the groups.

PMID- 16570249
TI  - Latino farmworker perceptions of the risk factors for occupational skin disease.
AB  - BACKGROUND: Farmworkers in the US constitute a medically underserved population
      at substantial risk for numerous environmental and occupational health problems.
      Most US farmworkers are Latino. Skin disease is one health problem to which
      farmworkers are particularly vulnerable. Interventions to reduce skin disease
      must be adapted to farmworkers' understanding of such disease, including their
      beliefs or knowledge of risk factors for skin disease. METHODS: Structured by the
      Explanatory Models of Illness framework, this analysis uses a qualitative design
      based on in-depth interviews with 30 Latino farmworkers (6 females, 24 males) to
      determine beliefs and perceptions of the causes of common occupational skin
      diseases in this population. Computer assisted, systematic procedures are used to
      analyze the verbatim transcripts of these interviews. RESULTS: Skin disease is a
      major concern among farmworkers because it affects work, social interaction, and
      other aspects of their lives. Farmworker beliefs and perceptions of skin disease
      causation can be integrated into a general model in which perceived risk factors
      include sun and heat, chemicals, plants, insects, moisture, hygiene, and
      contagion. Each of these factors is moderated by the individual's personal
      susceptibility to that cause. The interaction or combination of two or more
      factors is thought to amplify their individual effects. CONCLUSIONS: The
      farmworker model of skin disease causation suggests important content for health
      education to reduce skin disease among farmworkers.

PMID- 16570251
TI  - Modeling the impact of the components of long work hours on injuries and
      "accidents".
AB  - BACKGROUND: Many of the industrial disasters of the last few decades, including
      Three Mile island, Chernobyl, Bhopal, Exxon Valdez, and the Estonia ferry, have
      occurred in the early hours of the morning. Follow-up investigations concluded
      that they were at least partially attributable to human fatigue and/or error. The
      potential impact of long work hours on health and safety is a major concern that
      has resulted in various work hour regulations. METHODS: The risk of injuries and
      "accidents" (incidents) associated with features of work schedules from published
      epidemiological studies are pooled using an additive model to form a "Risk
      Index." The estimated risks of an incident for various standard work schedules
      are presented using the proposed model. RESULTS: The estimated risk of an injury
      or accident associated with any given number of weekly work hours varies
      substantially depending on how work hours are comprised. The risk depends on the
      length and type of shift, as well as the frequency of rest breaks. CONCLUSIONS:
      We conclude that placing a limit on the risk associated with a particular work
      schedule is likely more effective than setting daily, weekly or monthly work hour
      regulations in keeping workplace safety within acceptable limits.

PMID- 16570252
TI  - Musculoskeletal pain in ragpickers in a southern city in Brazil.
AB  - BACKGROUND: Ragpickers are informal workers who collect recyclable materials to
      earn a small wage. Their life and working conditions are extremely precarious.
      The ergonomic hazards and musculoskeletal pain in a sample of ragpickers in
      Pelotas, a city in southern Brazil are examined. METHODS: Two comparison groups
      were available: a matched sample of non-ragpickers from the same poor
      neighborhoods, and a random sample of the general population of the city. The
      cross-sectional study gathered data by interview on 990 individuals in 2004.
      Musculoskeletal pain was assessed using the Standardized Nordic Questionnaire.
      RESULTS: Ragpickers reported higher prevalences for most awkward postures and
      ergonomic exposures compared to neighbors with other demanding manual jobs. The
      prevalence within the last 12 months of low back pain (LBP), lower extremity pain
      (LEP), and upper extremity pain (UEP) among ragpickers were 49.2%, 45.1%, and
      34.9%, respectively; levels similar to those reported by neighborhood controls.
      Both ragpickers and non-ragpickers reported considerably higher ergonomic
      exposures, and more prevalent LBP, than the general population. CONCLUSIONS:
      Ragpickers experience many occupational hazards and ergonomic stressors. Their
      overall prevalence of musculoskeletal pain was similar to a comparison group with
      other physically demanding manual jobs. For LBP, this prevalence was
      substantially higher (49% vs. 35%) than in the general population.

PMID- 16570253
TI  - Duration of work disability: a comparison of self-report and administrative data.
AB  - BACKGROUND: Studies have used insurer-reported compensable days absent as an
      outcome measure when studying work-related injury or illness. Compared to self
      reported days absent, insurer data are less expensive to collect. Previous work
      has identified that insurer-claims data consistently underestimate the duration
      of days absent when compared to self-report. The objective of this study was to
      examine the agreement between the number of self-reported days absent from work
      following a compensable work-related injury and the number of insurer-reported
      compensation days paid, and to examine factors associated with the magnitude of
      the discrepancy between the number of self-reported days absent and the number of
      insurer-reported compensated days paid. METHODS: One hundred sixty six
      respondents who experienced a work-related injury were interviewed approximately
      200 days post-injury to assess the number of days absent from work. The number of
      days compensated by the insurer was compared to self-report using descriptive
      statistics and linear regression. RESULTS: Respondents who had yet to experience
      a return-to-work (RTW) had the largest median discrepancy followed by respondents
      with an unsustained RTW and finally sustained RTW. Respondents with upper
      extremity injuries, lower education, and lower RTW self-efficacy showed greater
      discrepancy between self-reported and compensated days absent. Among respondents
      who self-reported fewer days absent than insurer-compensated days absent an
      inverse relationship between firm size and discrepancy was noted. CONCLUSIONS:
      Researchers should be aware of the discrepancies between self-reported and
      compensated days absent. Future studies planning to incorporate days absent as an
      outcome variable should carefully consider what measure would be more appropriate
      and potentially collect both self-report and administrative data to assess the
      discrepancy.

PMID- 16570254
TI  - Illnesses and injuries reported by Latino poultry workers in western North
      Carolina.
AB  - BACKGROUND: Poultry processing is the largest sector of the meat products
      industry. Many workers are immigrants; few data exist on their illness and injury
      rates and the impact of workplace safety environment. METHODS: Survey interviews
      were conducted with a representative sample of 200 Latino poultry workers
      employed by three different companies in western North Carolina; topics included
      symptoms, work-related illnesses and injuries, and plant safety climate. RESULTS:
      Most respondents were <35 years of age and had been in the US <10 years.
      Frequency of self-reported symptoms was high, particularly for musculoskeletal
      symptoms. Despite symptoms, workers reported not missing work or seeking medical
      care. Occupational injuries and illnesses and symptoms varied by company. Between
      company differences in injury and illness rates were consistent with perceived
      safety and company provision of personal protective equipment. CONCLUSIONS:
      Symptoms reported exceeded rates reported by other community, clinical, and
      occupational samples. Findings suggest policy changes and research are needed to
      reduce the high rates of occupational illnesses and injuries in this vulnerable
      population.

PMID- 16570255
TI  - Adverse effects of asbestos exposure and smoking on lung function.
AB  - BACKGROUND: Exposure to asbestos is a well-recognized cause of both malignant and
      nonmalignant diseases of lung parenchyma and pleura. This study was conducted to
      determine the adverse effects of exposure to asbestos and smoking on pulmonary
      function. METHODS: Four hundred and sixty-eight workers who were occupationally
      exposed to asbestos for an average of 13 years were selected from an asbestos
      product factory in China. Of them, 85 workers were diagnosed with asbestosis.
      Additionally, 282 workers who had no experience of exposure to industrial dust
      were included as a control group. A questionnaire was administered during a face
      to-face interview and spirometric maneuvers and single-breath CO diffusing
      capacity (DL(CO)) were performed. RESULTS: Multivariate regression analysis
      showed that exposure to asbestos was more strongly associated with decreased
      forced vital capacity (FVC) and DL(CO), and asbestosis more strongly associated
      with decreased FVC, while smoking was a major contributing factor to reduced
      FEV1/FVC. The results were confirmed by a further analysis where the subjects
      were grouped exclusively by smoking, asbestos exposure, and chest radiographic
      changes. No interaction or joint effect was observed between asbestos exposure
      and smoking. CONCLUSIONS: This analysis suggested that asbestos and smoking might
      play independent roles, in which asbestos caused mainly a restrictive impairment,
      and smoking was a major causal factor for airway obstruction in the workers who
      were intensively exposed to asbestos.

PMID- 16570256
TI  - Immediate hypersensitivity type of occupational laryngitis in a welder exposed to
      welding fumes of stainless steel.
AB  - BACKGROUND: Although upper respiratory symptoms have been reported to occur in
      welders, occupational laryngitis of immediate hypersensitivity type due to
      welding fumes of stainless steel has not been previously reported. METHODS:
      Occupational laryngitis was diagnosed based on the specific challenge test
      combined with the patient's history of occupational exposure and laryngeal
      symptoms. RESULTS: During the past few years, a 50-year-old man had started to
      experience laryngeal symptoms while welding stainless steel. The welding
      challenge test with stainless steel caused significant changes in the laryngeal
      status 30 min after challenge: increased erythema, edema, and hoarseness of the
      voice. The referent inhalation challenge test by welding mild steel was negative.
      CONCLUSION: The welding of stainless steel should be included in the etiological
      factors of occupational laryngitis of immediate hypersensitivity type.

PMID- 16570257
TI  - Nerve conduction and sensorineural function in dental hygienists using high
      frequency ultrasound handpieces.
AB  - BACKGROUND: Oscillatory vibration from industrial power tools poses a well
      recognized risk of peripheral nerve injury. There have been reports of elevated
      vibrotactile perception thresholds (VPT) among dentists, dental technicians, and
      dental hygienists, using rotary devices and ultrasonics. Elevated VPTs are an
      indicator of small fiber nerve or mechanoreceptor injury, but the high
      frequencies associated with dental instruments are presumed by the ISO to exceed
      physiological response upper thresholds. This study examines nerve conduction and
      sensorineural deficits in dental hygienists. METHODS: A cross-sectional study of
      94 experienced dental hygienists was conducted to assess peripheral nerve
      function and clinical signs and symptoms. Specialized testing included
      measurement of VPTs for three different categories of mechanoreceptors, sensory
      nerve conduction tests with fractionated digit and palmar segments, and
      measurement of calibrated pinch force with force sensitive resistors (FSRs)
      during a simulated procedure. RESULTS: Chronic hand paresthesias were described
      by 44.7% of experienced dental hygienists. Sensory nerve conduction velocity
      (SNCV) across the wrist-palm segment of the median nerve. VPTs were particularly
      elevated at the FAII mechanoreceptor among experienced dental hygienists.
      Compared to participants without carpal tunnel syndrome (CTS), as defined by
      study criteria, 14 experienced hygienists with diagnosed CTS had almost twice the
      average weekly use of vibratory instruments -8.3 hr versus 4.5 hr, and had SNCV
      deficits along the digit -47.11 m/sec (+8.70) versus 42.57 m/sec (+8.25), and
      across the wrist -44.04 m/sec (+7.15) versus 41.36 m/sec (+9.27). There was a
      distinct subset of dental hygienists (27%) with a combination of low calibrated
      pinch force in simulations, subjective loss of strength and elevated VPTs,
      especially in the FAII mechanoreceptor population -110.82 db (+8.57) versus
      104.84 db (+6.80) in the rest of the cohort. This subset also had a higher
      prevalence of paresthesias (67% vs. 39%) and greater cumulative vibration
      exposure (OR = 1.206 [CI 1.005-1.448]), than other hygienists. CONCLUSIONS: The
      high levels of paresthesias observed among dental hygienists appear to be
      attributable to several pathophysiological mechanisms, including, sensory nerve
      demyelination at the carpal tunnel and intrinsic to the digits, and dysfunction
      of fingertip mechanoreceptors. A distinct sub-population appears to exhibit a
      high level of accumulated abnormality.

PMID- 16570258
TI  - Acute pesticide-related illness among emergency responders, 1993-2002.
AB  - BACKGROUND: Emergency responders are among the first to arrive at a pesticide
      related release event. Magnitude, severity, and risk factor information on acute
      pesticide poisoning among those workers is needed. METHODS: Survey data collected
      from the SENSOR-Pesticides, CDPR and HSEES programs between 1993 and 2002 from 21
      states were reviewed. Acute occupational pesticide-related illness incidence
      rates for each category of emergency responder were calculated, as were incidence
      rate ratios (IRR) among emergency responders compared to all other workers
      employed in non-agricultural industries. RESULTS: A total of 291 cases were
      identified. Firefighters accounted for 111 cases (38%), law enforcement officers
      for 104 cases (36%), emergency medical technicians for 34 cases (12%), and 42
      cases (14%) were unspecified emergency responders. Among the 200 cases with
      information on activity responsible for exposure, most were exposed while
      performing activities related to a pesticide release event (84%) and not
      involving patient care, while the remainder involved exposure to pesticide
      contaminated patients. A majority of cases were exposed to insecticides (51%).
      Most had low severity illnesses (90%). The incidence rate was highest for
      firefighters (39.1/million) and law enforcement officers (26.6/million). The IRRs
      were also elevated for these professions (firefighters, IRR = 2.67; law
      enforcement officers, IRR = 1.69). CONCLUSIONS: The findings suggest the need for
      greater efforts to prevent acute occupational pesticide-related illness among
      emergency responders.

PMID- 16570259
TI  - Surfactant protein B gene variations and susceptibility to lung cancer in
      chromate workers.
AB  - BACKGROUND: Hexavalent chromium has been extensively investigated regarding its
      mutagenicity and carcinogenicity; however, its mechanism for initiating and
      enhancing the development of lung cancer is still obscure. Biomarkers of
      exposure, effect or susceptibility are required for risk assessment and for
      epidemiologic research studies especially in occupational settings. Since the
      surfactant protein system (SP) is very important for normal lung function and for
      mediating local airway conditions and in the clearance of the upper respiratory
      tract from the occupational and environmental dusts, we hypothesize that SP genes
      may represent good candidates to study susceptibility for lung cancer. METHODS:
      Using PCR genotyping methods with gel electrophoresis and confirmation of results
      with precise DNA fragment size measurement on microchip electrophoresis, we
      analyzed SP-B intron-4 polymorphism in 230 subjects who were classified into
      groups; chromate-related lung cancer, control chromate workers who had not
      developed lung cancer, control individuals with non chromate-related
      adenocarcinoma or squamous cell carcinoma of the lungs, or healthy Japanese
      control individuals. RESULTS: Our results indicated that the SP-B variants
      (deletion/insertion) were significantly overrepresented (61.3%) in the chromate
      related lung cancer group than other groups (X2 = 47.6; DF = 4, P = 0.0001).
      There was a significant difference between the chromate lung cancer group and
      both of the control groups, healthy individuals and chromate workers who did not
      develop lung cancer, showing odds ratios (OR) with 95% confidence intervals (CI)
      of 21.9 (7.3-65.7) and 19.0 (3.78-95.4), respectively. Compared with 46 non
      chromate-related SCC of the lung, the SP-B variants were significantly
      overrepresented in the chromate-related SCC (18/28; 64.3%) than the non-chromate
      SCC (11/46; 23.9%) of the lung samples (X(2) = 10.27, P = 0.01), OR with 95% CI
      is 5.73 (2.05-16.01). CONCLUSION: These findings indicate a very strong
      association of the SP-B intron-4 variants with mechanisms that may enhance lung
      cancer susceptibility, especially in workers who are employed in chromate
      industry. Moreover, confirmation of such results may help to suggest adding the
      SP-B intron-4 typing to be one of the screening tests of the pre-placement
      medical examination to confirm that the worker has no variations of the SP-B gene
      before being engaged in a chromium-related industry, with the intention of
      providing proper medical counseling.

PMID- 16570260
TI  - Induction of leukemic-cell-specific cytotoxic T lymphocytes by autologous
      monocyte-derived dendritic cells presenting leukemic cell antigens.
AB  - Leukemic-dendritic cells (leukemic-DCs) have certain limitations, which include
      difficult generation in 30-40% of patients, and low levels of expression of
      several key molecules. Therefore, an alternative approach using monocyte-derived
      DCs pulsed with tumor antigens is required. We investigated the possibility of
      immunotherapy for AML using leukemic-cell-specific cytotoxic T lymphocytes that
      were stimulated in vitro by autologous DCs pulsed with tumor antigens. To
      generate DCs, CD14(+) cells were isolated from peripheral blood mononuclear cells
      using magnetic-activated cell sorting, and cultured in the presence of GM-CSF and
      IL-4. On day 6, maturation of DCs was induced by addition of cytokine cocktail
      (TNF-alpha, IL-1beta, IL-6, and prostaglandin E(2)) for 2 days, and then the
      mature DCs were pulsed with whole leukemic cell lysates or apoptotic leukemic
      cells. There were no differences in the phenotypic expressions of mature DCs
      generated by pulsing with or without leukemic antigens. The mature DCs pulsed
      with tumor cell lysates or apoptotic leukemic cells showed a higher
      allostimulatory capacity for allogeneic CD3(+) T cells as compared with mature
      non-pulsed DCs. Autologous CD3(+) T cells stimulated by the mature pulsed DCs
      showed more potent cytotoxic activities against autologous leukemic cells than
      those stimulated by mature non-pulsed DCs. These results suggest that use of DCs
      pulsed with leukemic cell lysates or apoptotic leukemic cells is a feasible
      alternative immunotherapeutic approach to overcome the limitations of leukemic
      DCs for the treatment of AML patients.

PMID- 16570261
TI  - Successful removal of Chlamydia pneumoniae from plateletpheresis products
      collected using automated leukoreduction hemapheresis techniques.
AB  - Chlamydia pneumoniae (Cp) is an obligate intracellular pathogen associated with a
      variety of maladies. Best known for its involvement in community-acquired
      pneumonia outbreaks; the potential role of Cp in diverse illnesses is a topic of
      increasing interest and investigation. Previous studies suggested that white
      blood cells from normal blood donors harboring this agent may be eliminated
      through leukoreduction by filtration. Here we examine the ability and efficacy of
      apheresis-related leukoreduction for its effect on the carriage and potential
      infectivity of these organisms in the preparation of platelet products. Matched
      pre-apheresis peripheral blood (PB) samples and product samples obtained from
      healthy plateletpheresis donors were analyzed for the presence and potential
      infectivity of Cp organisms by direct smear inspection and tissue culture
      techniques. Antibody seroreactivity directed towards the organism was assessed
      using a solid phase immunoassay. Forty-eight percent of the donor blood samples
      exhibited elevated anti-Cp antibody titers (> or =200). Specimens from 31 (27%)
      and 34 (30%) of 115 plateletpheresis donors were positive for the presence of Cp
      organisms in their pre-apheresis PB samples when analyzed by direct smear
      examination and culture, respectively. Examination of the 115 post-leukodepleted
      plateletpheresis product samples revealed only two (1.7%) and one (0.009%)
      product(s) to be smear-positive and culture-positive, respectively. Certain
      plateletpheresis donors may harbor infectious Cp organisms in circulating WBC.
      Collections from such donors of apheresis platelet products using standard
      apheresis leukoreduction strategies appear successful in markedly decreasing or
      eliminating the organisms found in the final products.

PMID- 16570262
TI  - Detailed screening for fetal anomalies and cardiac defects at the 11-13-week
      scan.
AB  - OBJECTIVE: To assess the diagnostic efficacy of the first-trimester anomaly scan
      including first-trimester fetal echocardiography as a screening procedure in a
      'medium-risk' population. METHODS: In a prospective study, we evaluated 3094
      consecutive fetuses with a crown-rump length (CRL) of 45-84 mm and gestational
      age between 11 + 0 and 13 + 6 weeks, using transabdominal and transvaginal
      ultrasonography. The majority of patients were referred without prior abnormal
      scan or increased nuchal translucency (NT) thickness, the median maternal age
      was, however, 35 (range, 15-46) years, and 53.8% of the mothers (1580/2936) were
      35 years or older. This was therefore a self-selected population reflecting an
      increased percentage of older mothers opting for prenatal diagnosis. The follow
      up rate was 92.7% (3117/3363). RESULTS: The prevalence of major abnormalities in
      3094 fetuses was 2.8% (86/3094). The detection rate of major anomalies at the 11
      + 0 to 13 + 6-week scan was 83.7% (72/86), 51.9% (14/27) for NT < 2.5 mm and
      98.3% (58/59) for NT >or= 2.5 mm. The prevalence of major congenital heart
      defects (CHD) was 1.2% (38/3094). The detection rate of major CHD at the 11 to 13
      + 6-week scan was 84.2% (32/38), 37.5% (3/8) for NT < 2.5 mm and 96.7% (29/30)
      for NT >or= 2.5 mm. CONCLUSION: The overall detection rate of fetal anomalies
      including fetal cardiac defects following a specialist scan at 11 + 0 to 13 + 6
      weeks' gestation is about 84% and is increased when NT >or= 2.5 mm. This extends
      the possibilities of a first-trimester scan beyond risk assessment for fetal
      chromosomal defects. In experienced hands with adequate equipment, the majority
      of severe malformations as well as major CHD may be detected at the end of the
      first trimester, which offers parents the option of deciding early in pregnancy
      how to deal with fetuses affected by genetic or structural abnormalities without
      pressure of time.

PMID- 16570263
TI  - French fetal biometry: reference equations and comparison with other charts.
AB  - OBJECTIVES: To construct new reference charts and equations for fetal biparietal
      diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur
      length (FL), using a large sample of fetuses examined at 15-40 weeks in France,
      and to compare them with previous references. METHODS: The study data were
      obtained over a continuous 1-year period from a population of pregnant women
      undergoing ultrasound examination. Excluded were those with a known abnormal
      karyotype or congenital malformation, multiple pregnancies, and those with no
      first-trimester dating based on crown-rump length. No fetuses were excluded on
      the basis of abnormal biometry or birth weight. For each measurement, separate
      regression models were fitted to estimate both the mean and the SD at each
      gestational age. RESULTS: Full biometric measurements were obtained for 19 647
      fetuses. New charts and reference equations are reported for BPD, HC, AC and FL.
      Prediction intervals for the new reference charts were similar to those of
      previous ones, whereas there were some differences in predicted centiles.
      CONCLUSION: We present new French reference charts and equations for fetal
      biometry. They can be used easily to compute centiles and Z-scores to control the
      quality of biometric assessments and to evaluate their performance relative to
      other references.

PMID- 16570264
TI  - Antenatal umbilical coiling index and Doppler flow characteristics.
AB  - OBJECTIVE: To evaluate whether a relationship exists between the antenatal
      umbilical coiling index (UCI) and umbilical cord Doppler flow characteristics.
      METHODS: During the fetal anatomical survey in 200 consecutive pregnant patients
      at 18-23 weeks' gestation, we recorded umbilical coiling patterns and blood flow
      characteristics. The antenatal UCI, calculated as a reciprocal value of the
      distance between a pair of umbilical cord coils, was compared with Doppler
      parameters including umbilical vein blood flow volume (in mL/min/kg), and mean
      resistance index (RI) and peak systolic velocity (PSV in cm/s) averaged from both
      umbilical arteries. RESULTS: A total of 154 patients met the inclusion criteria
      of singleton pregnancy and having adequate sonographic umbilical cord images,
      Doppler flow indices, and all demographic, antenatal and labor data. The mean
      antenatal UCI was 0.40, with 10th and 90th centiles of 0.20 and 0.60,
      respectively. The mean +/- SD umbilical artery RI and PSV and umbilical vein
      blood flow volume were 0.74 +/- 0.07, 25.1 +/- 6.4 cm/s, and 264 +/- 106
      mL/min/kg, respectively. All Doppler variables correlated significantly with
      antenatal UCI, with lower RI and higher PSV and umbilical vein blood flow volume
      values being associated with higher antenatal UCI (P = 0.016, P < 0.001, and P =
      0.032, respectively). However, when stratified by antenatal UCI into hyper-
      (above 90th centile), normo- (10th-90th centile), and hypocoiled (below 10th
      centile) umbilical cord groups, a significant difference was observed for PSV
      only (P = 0.016). CONCLUSION: It appears that umbilical cord coiling modulates
      noticeably blood flow through the umbilical cord. We speculate that more
      prominent umbilical coiling (higher antenatal UCI values) has a protective effect
      on blood flow in terms of decreased arterial resistance and higher blood flow
      velocities, as well as increased venous blood flow. However, due to lack of
      significant differences between Doppler characteristics when stratified by
      antenatal UCI into hypo-, normo-, and hypercoiled groups, the clinical
      implications of this observation are uncertain.

PMID- 16570265
TI  - Prenatal diagnosis of a nasal glioma in the mid trimester.
AB  - We report a case of fetal nasal glioma diagnosed at 21 weeks of gestation. The
      glioma appeared as a moderately hypoechoic mass arising from the junction between
      the medial aspect of the left orbit and the lateral aspect of the nose, and
      showing no internal vascularization on color and power Doppler ultrasonography.
      Fetal magnetic resonance imaging (MRI) excluded the possibility of an
      encephalocele by ruling out underlying bone defects. After an uneventful
      pregnancy, the nasal glioma was resected without complications at 4 months of
      age. The differential diagnosis of fetal paranasal facial masses is discussed.

PMID- 16570266
TI  - Birth seasonality and interbirth interval of captive Rhinopithecus bieti.
AB  - This study, which is based on 10 years of birth records, shows that black-and
      white snub-nosed monkeys (Rhinopithecus bieti) in captivity display marked birth
      seasonality. The birth season starts in December and ends in June, with a peak
      from March to May, and a median birth date of April 10. More male infants than
      female ones are born in captivity. More males were born at the Kunming Institute
      of Zoology (KIZ) than at the Kunming Zoo (KZ). Of 17 interbirth intervals (IBIs),
      29% were from females that had lost an infant at <1 year of age or experienced
      stillbirth, and 71% were from females whose infant survived more than 1 year. The
      mean IBI for the former group (428+/-SD 87 days) was significantly shorter than
      that for the latter group (706+/-71 days), in agreement with reports of other
      Colobine species. Infant mortality was lower in captivity than in the field,
      which may reflect the relatively stable food availability and climate in
      captivity compared to the harsh conditions in the wild.

PMID- 16570267
TI  - Evaluating the effects of eating disorder memoirs on readers' eating attitudes
      and behaviors.
AB  - OBJECTIVE: More than 50 individuals have published eating disorder (ED) memoirs.
      The current study was the first to test whether memoirs affect readers' eating
      attitudes and behaviors, and whether they normalize and/or glamorize EDs. METHOD:
      Fifty female undergraduates read an ED or control memoir. Before and afterward,
      participants completed the 26-item Eating Attitudes Test (EAT-26), the Eating
      Disorders Inventory (EDI) Drive for Thinness subscale, a measure of perceived ED
      symptom prevalence, and an Implicit Association Test (IAT) measuring associations
      between anorexia and glamour/danger. RESULTS: Participants in the ED condition
      did not demonstrate significant changes in the EAT-26, the EDI Drive for Thinness
      subscale, perceived symptom prevalence, or IAT associations compared with
      controls. Before reading, the EAT-26 and EDI Drive for Thinness subscale
      correlated positively with perceived symptom prevalence and strength of the IAT
      association between anorexia and glamour. CONCLUSION: ED memoirs appear to have
      little effect on undergraduates' eating attitudes and behaviors. Future research
      should investigate whether memoirs affect individuals with preexisting eating
      pathology, who may normalize and glamorize ED symptoms.

PMID- 16570268
TI  - Familial risks of esophageal cancer among the Turkmen population of the Caspian
      littoral of Iran.
AB  - In northeastern Iran, there is an area of high incidence of esophageal cancer,
      which is populated by residents of Turkmen ancestry. Several environmental risk
      factors for esophageal cancer have been proposed, but the roles of familial and
      genetic factors have not been studied extensively in the Turkmen population. We
      evaluated the importance of familial risk factors for esophageal cancer by
      performing a case-control study of 167 cases of esophageal squamous cell
      carcinoma and 200 controls of Turkmen ethnicity. Detailed family pedigrees of the
      cases and controls were constructed, which documented all cancers in first- and
      second-degree relatives. The actuarial risk of cancer was then estimated in 2,097
      first-degree relatives of cases and 2,783 first-degree relatives of the controls.
      A hazard ratio was constructed, based on a comparison of the 2 cumulative
      incidence curves. The risk to age 75 of esophageal cancer in the first-degree
      relatives of Turkmen patients with esophageal cancer was 34% versus 14% for the
      first-degree relatives of the controls (hazard ratio = 2.3; p = 3 x 10(-8)).
      Cases (9.6%) reported that their parents were related, versus 2.5% of the
      controls who reported this. (odds ratio = 4.1; p value = 0.006). Familial factors
      are important in the etiology of esophageal cancer among the Turkmen residents of
      Iran. The hazard ratio of 2.3 for cancer among first-degree relatives is
      consistent with an important contribution of heritable factors. It will be of
      interest to perform marker studies to establish which genes are responsible.

PMID- 16570269
TI  - Nicotine induces the fragile histidine triad methylation in human esophageal
      squamous epithelial cells.
AB  - The fragile histidine triad (FHIT) gene has been proposed to have an important
      role in very early carcinogenesis. Methylation of the FHIT gene is associated
      with transcriptional inactivation in esophageal squamous cell carcinoma, and FHIT
      inactivation has been linked to smoking-related carcinogenesis. In this study, we
      confirmed methylation of the FHIT gene in human esophageal squamous epithelial
      cells (HEECs) and examined whether nicotine induced alteration of FHIT.
      Methylation status in the promoter region of the FHIT gene and p16(INK4A) gene
      was determined by methylation-specific PCR in HEECs exposed to nicotine under
      various conditions. Methylation status of the FHIT gene was confirmed by DNA
      sequencing analysis. Protein expression of Fhit and the DNA methyltransferases
      (DNMTs) DNMT1 and DNMT3a were assessed by immunoblot analysis. In the absence of
      nicotine, methylation of the FHIT gene and attenuation of Fhit protein were not
      detected in HEECs. Nicotine induced the methylation of FHIT gene and attenuated
      Fhit protein in association with increased expression of DNMT3a. Reexpression of
      Fhit protein in HEECs was found after cessation of moderate- to long-term
      exposure to nicotine. Our results show that nicotine induces methylation of the
      FHIT gene followed by loss of Fhit protein expression in HEECs. Continuous
      smoking may thus increase the risk of esophageal cancer.

PMID- 16570271
TI  - Cervical carcinoma and reproductive factors: collaborative reanalysis of
      individual data on 16,563 women with cervical carcinoma and 33,542 women without
      cervical carcinoma from 25 epidemiological studies.
AB  - The International Collaboration of Epidemiological Studies of Cervical Cancer has
      combined individual data on 11,161 women with invasive carcinoma, 5,402 women
      with cervical intraepithelial neoplasia (CIN)3/carcinoma in situ and 33,542 women
      without cervical carcinoma from 25 epidemiological studies. Relative risks (RRs)
      and 95% confidence intervals (CIs) of cervical carcinoma in relation to number of
      full-term pregnancies, and age at first full-term pregnancy, were calculated
      conditioning by study, age, lifetime number of sexual partners and age at first
      sexual intercourse. Number of full-term pregnancies was associated with a risk of
      invasive cervical carcinoma. After controlling for age at first full-term
      pregnancy, the RR for invasive cervical carcinoma among parous women was 1.76
      (95% CI: 1.53-2.02) for > or => or =7 full-term pregnancies compared with 1-2.
      For CIN3/carcinoma in situ, no significant trend was found with increasing number
      of births after controlling for age at first full-term pregnancy among parous
      women. Early age at first full-term pregnancy was also associated with risk of
      both invasive cervical carcinoma and CIN3/carcinoma in situ. After controlling
      for number of full-term pregnancies, the RR for first full-term pregnancy at age
      <17 years compared with > or => or =25 years was 1.77 (95% CI: 1.42-2.23) for
      invasive cervical carcinoma, and 1.78 (95% CI: 1.26-2.51) for CIN3/carcinoma in
      situ. Results were similar in analyses restricted to high-risk human papilloma
      virus (HPV)-positive cases and controls. No relationship was found between
      cervical HPV positivity and number of full-term pregnancies, or age at first full
      term pregnancy among controls. Differences in reproductive habits may have
      contributed to differences in cervical cancer incidence between developed and
      developing countries.

PMID- 16570270
TI  - KIF14 mRNA expression is a predictor of grade and outcome in breast cancer.
AB  - Gain of chromosome 1q is a hallmark of breast cancer, and likely reflects
      oncogene amplification. We previously identified mitotic kinesin KIF14 (kinesin
      family member 14) as an overexpressed candidate oncogene in the 1q31.3-1q32.1
      minimal region of genomic gain in breast cancer cell lines. KIF14 also showed
      high expression in other cancers, notably an association with survival in lung
      tumors. We now report KIF14 expression in 99 primary breast tumors and 10 normal
      breast controls. Measured by real-time RT-PCR, KIF14 was overexpressed 10-fold on
      average in tumors relative to normals (t test p = 0.000054); expression increased
      with grade (ANOVA p = 0.000006). Infiltrating ductal carcinomas had higher KIF14
      levels than lobular (p = 0.017), and estrogen receptor (ER) negative tumors had
      higher KIF14 levels than ER positive tumors (t test p = 0.030). KIF14 expression
      correlated positively with Ki-67 mRNA level (Spearman r = 0.692, p = 0.000001),
      fraction of positive nodes (r = 0.227, p = 0.024) and percent invasive cells (r =
      0.360, p = 0.0002), and negatively with percent fatty stroma (r = -0.258, p =
      0.010) and percent normal epithelium (r = -0.291, p = 0.003). KIF14 expression is
      thus tumor-specific and increased in more aggressive tumors. Indeed, KIF14
      expression predicted overall survival (univariate Cox p = 0.010), with an odds
      ratio of 3.60 (1.37-9.48), in 50 tumors with available outcome data. KIF14
      overexpression also predicted decreased disease-free survival (log-rank p =
      0.049). These findings are the first evidence of association between expression
      of a mitotic kinesin and prognostic variables in breast cancer.

PMID- 16570272
TI  - Inhibitors of the PI3-kinase/Akt pathway induce mitotic catastrophe in non-small
      cell lung cancer cells.
AB  - Non-small cell lung cancer cells (NSCLC) are more resistant to anticancer
      treatment as compared with other types of cancer cells. Recently (Hemstrom et
      al., Exp Cell Res 2005;305:200-13) we showed that apoptosis of U1810 NSCLC cells
      induced by the staurosporine analog PKC 412 correlated with inhibition of Akt and
      ERK1/2, suggesting the involvement of these kinases in cell survival. Here we
      investigated the contribution of the PI3-kinase/Akt and MEK/ERK pathways to
      survival of NSCLC cells. The two signaling pathways were studied by using
      different combinations of the PI3-kinase inhibitors LY-294002 and wortmannin, the
      Akt activator Ro 31-8220, the MEK inhibitor PD 98059 and PKC 412. PI3-kinase
      inhibitors induced apoptosis-like death in U1810 cells. H157 cells in general
      were relatively resistant to PI3 kinase/Akt inhibitors yet these compounds
      sensitized cells to the DNA-damaging drug VP-16, while Ro 31-8220 could not. PD
      98059 only had a sensitizing effect on H157 cells when combined with PI3-kinase
      inhibition and VP-16. Morphological data indicated that LY-294002 and PKC 412
      induced cell death at anaphase and metaphase, respectively, suggesting death by
      mitotic catastrophe. Analyzes of cells blocked in G2/M-phase by nocodazol
      revealed that LY-294002 increased, while PKC 412 decreased histone H3
      phosphorylation, suggesting that LY-294002 allowed, while PKC 412 inhibited cells
      to leave M-phase. Flow cytometric analysis of cell cycle distribution
      demonstrated that LY-294002 allowed cells to leave G2/M phase, while PKC 412
      inhibited cytokinesis, resulting in formation of multinucleated cells. These
      results indicate that sensitization of NSCLC cells by PI3-kinase inhibition
      involves interplay between cell cycle regulation, mitotic catastrophe and
      apoptosis.

PMID- 16570273
TI  - Zoledronic acid slows down rat primary chondrosarcoma development, recurrent
      tumor progression after intralesional curretage and increases overall survival.
AB  - Chondrosarcoma is a difficult musculoskeletal tumor to treat. Surgical treatment
      leads to severe disability, with high rates of local recurrence and life threat.
      No adjuvant therapy is effective in differentiated chondrosarcomas.
      Bisphosphonates (BPs) are a class of molecules which is effective in malignant
      bone diseases. The aim of the present study was to determine the effects of
      zoledronic acid (ZOL) on chondrosarcoma tumor progression. ZOL was tested in vivo
      (s.c. 100 microg/kg, twice a week) in a rat chondrosarcoma model and in vitro
      (10(-7)-10(-4) M) on cells derived from this model. Two types of animal models
      were assessed, the first simulated development after intralesional curettage, the
      second nonoperative development of the tumor. Cell proliferation, caspase-1, -3
      activities and cell cycle analysis were studied. The results revealed that ZOL
      slows down primary tumor development, tumor progression after intralesional
      curretage and increases overall survival. ZOL inhibits cell proliferation and
      increases cell death, with no significant variation of caspase-1 and -3
      activities and cell cycle profiles. The present study demonstrates for the first
      time that in addition to surgery, the therapy of chondrosarcoma with BPs might be
      beneficial. Because of these first results, new therapeutic approaches of
      chondrosarcoma must be considered, mainly for low grade chondrosarcoma when
      disabling operation is planned and when only intralesional resection can be
      undertaken.

PMID- 16570274
TI  - Adulthood consumption of preserved and nonpreserved vegetables and the risk of
      nasopharyngeal carcinoma: a systematic review.
AB  - The incidence rates of nasopharyngeal carcinoma (NPC) are dramatically higher in
      certain regions of Asia compared to the rest of the world. Few risk factors for
      NPC are known; however, in contrast to the hypothesized health benefits of
      nonpreserved vegetables, it is thought that preserved vegetable intake may play a
      role in contributing to the higher incidence of NPC in high-risk regions.
      Therefore, the purpose of this study was to systematically review the
      epidemiologic evidence on the associations between adulthood intake of preserved
      and nonpreserved vegetables and NPC risk. A search of the epidemiological
      literature from 1966 to 2004 was performed using several bibliographic databases,
      including PubMed and the Chinese Biomedical Literature Database System. There
      were no language restrictions. Meta-analysis was conducted to obtain pooled odds
      ratios (ORs) for the highest-versus-lowest categories of preserved and
      nonpreserved vegetable intake. A total of 16 case-control studies were identified
      in the search. Results showed that highest-versus-lowest preserved vegetable
      intake was associated with a 2-fold increase in the risk of NPC (Random Effects
      Odds Ratio (RE OR) 2.04; 95% Confidence Limits (CL) 1.43, 2.92). Conversely, high
      nonpreserved vegetable intake was associated with 36% decrease in the risk of NPC
      (RE OR 0.64; 95% CL 0.48, 0.85). Findings for both preserved and nonpreserved
      vegetables were consistent across vegetable type and by country of study. Further
      research in high-risk areas to gain insight into the risk associated with
      preserved vegetables and protection associated with nonpreserved vegetables may
      advance understanding of NPC and yield clues for prevention.

PMID- 16570275
TI  - Aflatoxin B1 and polycyclic aromatic hydrocarbon adducts, p53 mutations and p16
      methylation in liver tissue and plasma of hepatocellular carcinoma patients.
AB  - Elevated aflatoxin B(1)-albumin adducts (AFB(1)-Alb) have been associated with an
      increased risk for HCC development. However, there are no studies in humans,
      correlating albumin adducts in blood with liver DNA adducts. Forty frozen tumor
      tissues and 39 paired plasma samples from HCC patients were collected in Taiwan,
      to determine the relationship between albumin adducts in blood and DNA adducts in
      liver tissue as well as mutations in p53 and methylation of p16. AFB(1)- and
      polycyclic aromatic hydrocarbon (PAH)-DNA adducts in tissue and albumin adducts
      in plasma were determined by immunohistochemistry and competitive ELISA,
      respectively. Plasma AFB(1)-Alb adducts in subjects with low, medium and high
      levels of AFB(1)-DNA adducts in tumor tissues were 51.0 +/- 36.5, 70.5 +/- 48.1
      and 84.9 +/- 48.2 fmol/mg, respectively (p(trend) = 0.05). No significant
      correlation was found for PAH. Fourteen of 40 (36%) tissues were positive for
      mutant p53 protein by immunohistochemistry; 11 of 40 tissue DNA samples (28%)
      were positive for p53 mutations, but not their corresponding plasma DNAs. p16 was
      methylated in 24 of 40 (62%) tissues and 12 of 39 (32%) plasma DNAs. Significant
      correlations were observed between AFB(1)-Alb adducts and p53 mutations and p16
      methylation. These data suggest that genetic, epigenetic and environmental
      exposure biomarkers in plasma may help in estimating the risk for the development
      of HCC.

PMID- 16570276
TI  - The characterization of the invasion phenotype of uveal melanoma tumour cells
      shows the presence of MUC18 and HMG-1 metastasis markers and leads to the
      identification of DJ-1 as a potential serum biomarker.
AB  - Uveal malignant melanoma (UM) is the most frequent primary intraocular tumour in
      adult humans. Because the survival rate of patients with UM has changed little in
      the past few decades, a better understanding of the molecular events governing UM
      development and the identification of markers indicating the potential for
      metastasis at the time of diagnosis are necessary to design improved and more
      specific treatments. In this study, we investigated UM tumour development by
      comparing two recently established UM cultures with different invasion potential
      by two-dimensional gel electrophoresis. Protein features expressed differentially
      were identified by mass spectrometric analysis. Potential markers were assayed in
      both cultures and in long-term established UM cell lines (UW-1, OCM-1, SP6.5 and
      92.1) by Western blotting and their role in invasion analysed using Matrigel
      membranes. Comparative analysis revealed that UM cultures with low- and high
      grade invasion potential differ in their cellular metabolism and, more
      interestingly, in several cancer-associated proteins, including those implicated
      in cell adhesion and migration, proliferation and various oncogenes. Our data
      indicate a correlation between MUC18 and HMG-1 expression and the invasiveness of
      UM cells. We also demonstrate the expression and secretion of DJ-1 oncoprotein by
      UM cells. We suggest a possible role for MUC18 and HMG-1 proteins in UM cell
      invasion. The secretion of DJ-1 by UM cells, and the ability to detect this
      protein in UM patients' sera implicate it as a potential noninvasive biomarker
      for this malignancy.

PMID- 16570277
TI  - Association of meningioma with reproductive factors.
AB  - Meningiomas occur more commonly in females. The coincidence between meningioma
      and breast cancer and case reports of tumor growth during pregnancy support a
      hormonal hypothesis. A case control study was conducted to investigate this.
      Female subjects treated between 1987 and 1992 were identified from 3 hospitals in
      the Chicago area. Female spouses of male back pain patients were recruited as
      controls. A self-administered mail questionnaire focused on exogenous, endogenous
      and other hormonal factors, personal and family medical history as well as
      radiation exposures. Odds ratios and 95% confidence intervals were estimated
      using crude, stratified and multivariable logistic models including 219 cases and
      260 controls. Participation rates were 86% among cases and 75% among controls. An
      increased odds ratio (OR) was observed comparing African Americans to Caucasians
      [OR = 2.4, 95% confidence interval (CI) = 1.0-6.1]. A protective effect was
      observed for pregnancy, which increased with number and age at first pregnancy.
      The odds ratio for 3 or more pregnancies compared to none was 0.3 (95% CI = 0.2
      0.6). Age at menarche or total period of hormonal activity was not protective.
      Ever smokers showed a decreased odds ratio for meningioma (OR = 0.6, 95% CI = 0.4
      0.9). The increased odds ratios with African Americans was retained in post
      menopausal women, while the protective odds ratios for pregnancy, smoking and
      oral contraceptives (OCs) became stronger in pre-menopausal women. The pattern by
      duration and timing of use does not suggest an etiologic role for OCs or hormone
      replacement therapy. These data add to the evidence that factors known to
      influence endogenous hormones (pregnancy and indirectly smoking) may have
      protective effects for meningiomas primarily in premenopausal women.

PMID- 16570278
TI  - Presence of high-risk human papillomavirus DNA in penile carcinoma predicts
      favorable outcome in survival.
AB  - There is evidence that a subset of penile carcinomas is caused by infection with
      high-risk human papillomavirus (HPV). However, extensive studies on the possible
      influence of HPV infection on clinical outcome of penile cancer are lacking. This
      investigation is aimed to examine the prevalence of high-risk HPV in a large
      series of penile squamous-cell carcinomas (SCCs) and to determine the
      relationship between HPV and survival. Formalin-fixed, paraffin-embedded tumor
      specimens of 171 patients with penile carcinoma were tested for high-risk HPV DNA
      presence by GP5+/6+-PCR. The clinical course of the patients and the
      histopathological characteristics of the primary tumors were reviewed. High-risk
      HPV DNA was detected in 29% of the tumors, with HPV 16 being the predominant
      type, accounting for 76% of high-risk HPV containing SCCs. Disease-specific 5
      year survival in the high-risk HPV-negative group and high-risk HPV-positive
      group was 78% and 93%, respectively (log rank test p = 0.03). In multivariate
      analysis, the HPV status was an independent predictor for disease-specific
      mortality (p = 0.01) with a hazard ratio of 0.14 (95% CI: 0.03-0.63). Our results
      indicate that the presence of high-risk HPV (29%) confers a survival advantage in
      patients with penile carcinoma.

PMID- 16570279
TI  - Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in
      HPV 16, 18, 31 and 33-positive women with normal cytology.
AB  - An increased high-risk human papillomavirus (hrHPV) viral load in cervical
      scrapings has been proposed as a determinant for high-grade cervical
      intraepithelial neoplasia (CIN) and cervical cancer (> or =CIN 2), but data so
      far for HPV types different from HPV 16 are limited and inconsistent. In
      addition, a viral load threshold to distinguish hrHPV positive women without > or
      =CIN 2 still has not been defined. Here, we used baseline cervical scrapings of
      women with normal cytology participating in a large population-based cervical
      screening trial (i.e. POBASCAM) who were GP5+/6+-PCR positive for 4 common hrHPV
      types, i.e. HPV 16, 18, 31 or 33, as a reference to arbitrarily define various
      viral load thresholds (i.e. 25th, 33rd, 50th, 67th and 75th percentiles of the
      lowest viral load values) for distinguishing women having single infections with
      these types without high-grade CIN. Viral load assessment was performed by real
      time type-specific PCR. The viral load threshold values were subsequently
      validated on abnormal cervical scrapes of 162 women with underlying,
      histologically confirmed CIN lesions containing 1 of these 4 hrHPV types. All 59
      women with CIN 3 had viral load levels that were higher than those of 33% of the
      women with normal cytology containing the respective hrHPV type detectable by
      GP5+/6+-PCR (i.e. higher than the 33rd percentile of viral load). By using this
      33rd percentile viral load cut-off, sensitivity for CIN 3 of 100% (95% CI 93.9
      100) was obtained. Hence, application of this viral load threshold would increase
      the specificity of HPV testing for HPV 16, 18, 31 and 33-associated prevalent CIN
      3 without the cost of a marked reduction in sensitivity. In practice, on the
      basis of viral load analysis, a less aggressive management can be foreseen for
      33% of the women with normal cytology participating in a population-based
      screening program who are GP5+/6+-PCR positive for HPV 16, 18, 31 or 33.

PMID- 16570280
TI  - Methodological issues in international comparison of interval breast cancers.
AB  - International comparisons of interval cancers (IC) are important to better
      understand the relationship between programmes' performance and screening
      practices. In this respect, differences in (i) definition, (ii) identification
      and (iii) quantification of IC have received little attention. To examine these 3
      comparability issues and activities involving IC, an assessment was conducted
      among member countries of the International Breast Cancer Screening Network, and
      the impact of accuracy of identification and quantification practices was
      estimated using 1996-98 data from the Dutch breast cancer screening programme.
      Information was obtained from 19 screening programmes in 18 countries, 16 of
      which acknowledged the coexistence of opportunistic screening. IC data were
      collected to evaluate performance of the screening programme (100% of programmes)
      and the radiologists (89%); 53% of programmes had a designated review process for
      IC. Most programmes (84%) agreed with the European Guidelines definition of IC,
      but a case situation exercise evidenced substantial discrepancy in classification
      of cancers that occurred after a positive screen. Completeness of identification
      of IC appears to contribute most to international variation, and cannot be easily
      controlled for in methodologically rigorous comparisons. Statistically
      significant differences of about 4% were measured between quantification methods
      for IC. An operational definition of IC is proposed to enhance international
      comparability. Valid comparisons of IC are possible with careful attention to the
      definition but true differences in IC frequency across screening programmes
      should exceed 10% to be possibly indicative of real differences between
      programmes.

PMID- 16570281
TI  - Effects of single nucleotide polymorphisms in human N-acetyltransferase 2 on
      metabolic activation (O-acetylation) of heterocyclic amine carcinogens.
AB  - N-Acetyltransferase 2 (NAT2) catalyzes the O-acetylation of N-hydroxy
      heterocyclic amines such as N-hydroxy-2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (N--OH--MeIQx) and N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5
      b] pyridine (N--OH --PhIP) to DNA binding metabolites that initiate mutagenesis
      and carcinogenesis. NAT2 acetylator phenotype is associated with increased cancer
      risk. Single nucleotide polymorphisms (SNPs) have been identified in the NAT2
      coding region. Although the effects of these SNPs on N-acetyltransferase activity
      have been reported, very little is known regarding their effects on O-acetylation
      activity. To investigate the functional consequences of SNPs in the NAT2 coding
      region on the O-acetylation of N-hydroxy heterocyclic amines, reference NAT2*4
      and NAT2 variant alleles possessing one were cloned and expressed in yeast
      (Schizosaccaromyces pombe). T111C, C282T, C481T, C759T, and A803G (K268R) SNPs
      did not significantly (p > 0.05) modify O-acetylation catalysis with N--OH--PhIP
      or N--OH--MeIQx. C190T (R64W), G191A (R64Q), T341C (I114T), A434C (E145P), G590A
      (R197Q) and A845C (K282T) significantly (p < 0.01) reduced the O-acetylation of
      both N--OH--PhIP and N--OH--MeIQx, whereas G857A (G286E) significantly (p < 0.05)
      decreased catalytic activity towards the O-acetylation of N--OH--MeIQx but not N-
      OH--PhIP. These results have important implications towards the interpretation of
      molecular epidemiological studies of NAT2 genotype and cancer risk.

PMID- 16570282
TI  - 4-HPR modulates gene expression in ovarian cells.
AB  - Ovarian cancer has a high rate of recurrence and subsequent mortality following
      chemotherapy despite intense efforts to improve treatment outcomes. Recent trials
      have suggested that retinoids, especially 4-(N-hydroxyphenyl) retinamide (4-HPR),
      play an important role as a chemopreventive agent and are currently being used in
      clinical trials for ovarian cancer chemoprevention as well as treatment. This
      study examines the mechanism of its activity in premalignant and cancer cells. We
      investigated the modulation of gene expression by 4-HPR in immortalized ovarian
      surface epithelial (IOSE) cells and ovarian cancer (OVCA433) cells with DNA
      microarray. Real time RT-PCR and western blotting were used to confirm the
      microarray results and metabolic changes were examined with optical fluorescence
      spectroscopy. 4-HPR resulted in an up-regulation of expression of proapoptotic
      genes and mitochondrial uncoupling protein in OVCA433 cells and modulation of the
      RXR receptors in IOSE cells, and down-regulation of mutant BRCA genes in both
      IOSE and OVCA433 cells. 4-HPR had a larger effect on the redox in the 433 cells
      compared to IOSE. These findings suggest that 4-HPR acts through different
      mechanisms in premalignant ovarian surface cells and cancer cells, with a
      preventive effect in premalignant cells and a treatment effect in cancer cells.

PMID- 16570283
TI  - Small molecule drug activity in melanoma models may be dramatically enhanced with
      an antibody effector.
AB  - Monoclonal antibody (mAb) 38C2 belongs to a group of catalytic antibodies that
      were generated by reactive immunization and contains a reactive lysine. 38C2
      catalyzes aldol and retro-aldol reactions, using an enamine mechanism, and
      mechanistically mimics natural aldolase enzymes. In addition, mAb 38C2 can be
      redirected to target integrins alpha(v)beta(3) and alpha(v)beta(5) through the
      formation of a covalent bond between a beta-diketone derivative of an arginine
      glycine-aspartic acid (RGD) peptidomimetic and the reactive lysine residue in the
      antibody combining site to provide the chemically programmed mAb cp38C2. In this
      study, we investigated the potential of enhancing the activity of receptor
      binding small molecule drug (SCS-873) through antibody conjugation. Using a M21
      human melanoma xenograft model in nude mice, cp38C2 inhibited the growth of the
      tumor by 81%. The chemically programmed antibody was shown to be highly active at
      a low concentration while SCS-873 alone was ineffective even at dosages 1,000
      fold higher than those used for the chemically programmed antibody. In vitro
      programming of the catalytic antibody was shown to be as effective as in vivo
      programming. In an experimental metastasis assay, treatment with mAb cp38C2
      significantly prolonged overall survival of tumor-bearing severe combined immuno
      deficient (SCID) mice when compared to treatment with unprogrammed mAb 38C2, SCS
      873 alone or the integrin-specific monoclonal antibody LM609. In vitro, cp38C2
      inhibited human and mouse endothelial and human melanoma cell adhesion, migration
      and invasion. Additionally, cp38C2 inhibited human and mouse endothelial cell
      proliferation and was active in complement-dependent cytotoxicity assays. These
      studies establish the potential of chemically programmed monoclonal antibodies as
      a novel and effective class of immunotherapeutics that combine the merits of
      traditional small molecule drug design with immunotherapy.

PMID- 16570284
TI  - Insulin-like growth factor binding protein 3 as an anticancer molecule in Ewing's
      sarcoma.
AB  - The IGF/IGF-IR system plays a major role in the pathogenesis and progression of
      Ewing's sarcoma. In this article, the authors evaluated whether the insulin-like
      growth factor binding protein-3 (IGFBP-3), a molecule with growth-inhibitory and
      proapoptotic activities, may be exploited for therapeutic applications in the
      treatment of Ewing's sarcoma (EWS). Expression of IGFBP-3 was analyzed in a panel
      of EWS cell lines and clinical samples. Parameters related to malignancy (growth
      in anchorage-independent conditions, migration, invasion and angiogenesis
      properties) were studied to establish the potential in vitro anticancer effects
      of exogenous IGFBP-3. The activity of the molecule against metastasis was
      analyzed by taking advantage of selected clones in which IGFBP-3 endogenous
      production was induced by gene transfection. The authors observed a generally low
      expression of IGFBP-3 either in a panel of EWS cell lines or clinical samples.
      Exogenous IGFBP-3 remarkably inhibits EWS growth, both in monolayer and anchorage
      independent conditions, and significantly reduces cell motility. Forced
      expression of IGFBP-3 in TC-71 EWS cells confirms the growth and migratory
      effects observed with the exogenous protein, decreases the production or activity
      of the matrixmetalloprotease MMP-9 and vascular endothelial factor (VEGF)-A and
      abrogates EWS metastasis ability. IGFBP-3 acts mainly through IGF-dependent
      mechanisms and the protein may therefore represent an alternative strategy to
      inhibit IGF-IR functions. The data indicate IGFBP-3 as a molecule of therapeutic
      potential in EWS.

PMID- 16570286
TI  - Brain cancer mortality and potential occupational exposure to lead: findings from
      the National Longitudinal Mortality Study, 1979-1989.
AB  - We evaluated the association between potential occupational lead exposure and the
      risk of brain cancer mortality in the National Longitudinal Mortality Study
      (NLMS), which is a prospective census-based cohort study of mortality among the
      noninstitutionalized United States population (1979-1989). The present study was
      limited to individuals for whom occupation and industry were available (n =
      317,968). Estimates of probability and intensity of lead exposure were assigned
      using a job-exposure matrix (JEM). Risk estimates for the impact of lead on brain
      cancer mortality were computed using standardized mortality ratio (SMR) and
      proportional hazards and Poisson regression techniques, adjusting for the effects
      of age, gender and several other covariates. Brain cancer mortality rates were
      greater among individuals in jobs potentially involving lead exposure as compared
      to those unexposed (age- and gender-adjusted hazard ratio (HR) = 1.5; 95%
      confidence interval (CI) = 0.9-2.3) with indications of an exposure-response
      trend (probability: low HR = 0.7 (95% CI = 0.2-2.2), medium HR = 1.4 (95% CI =
      0.8-2.5), high HR = 2.2 (95% CI = 1.2-4.0); intensity: low HR = 1.2 (95% CI = 0.7
      2.1), medium/high HR = 1.9 (95% CI = 1.0-3.4)). Brain cancer risk was greatest
      among individuals with the highest levels of probability and intensity (HR = 2.3;
      95% CI = 1.3-4.2). These findings provide further support for an association
      between occupational lead exposure and brain cancer mortality, but need to be
      interpreted cautiously due to the consideration of brain cancer as one disease
      entity and the absence of biological measures of lead exposure.

PMID- 16570285
TI  - Chromosome 9 deletions are more frequent than FGFR3 mutations in flat urothelial
      hyperplasias of the bladder.
AB  - Flat urothelial hyperplasias (FUHs) in patients with papillary bladder tumours
      frequently show deletions of chromosome 9, suggesting that FUH could be the first
      neoplastic step in the development of papillary bladder cancer. FGFR3 mutations
      are frequent in non-invasive papillary tumours with low risk of progression. Our
      aim was to investigate the frequency of FGFR3 mutations and deletions of
      chromosomes 9p/q and 8p/q in FUH. Thirty FUH and 9 simultaneous or consecutive
      tumours were detected by 5-ALA-based photodynamic cystoscopy. DNA was isolated
      from frozen sections and whole genome amplification was done by I-PEP-PCR,
      followed by LOH analysis on chromosomes 8p/q and 9p/q. FGFR3 mutations were
      detected by SNaPshot analysis. LOH analysis on FUH revealed deletions at 9p/q
      (11/30, 37%) and 8p/q (3/30, 10%). FGFR3 mutations were found in 7/30 FUH (23%).
      Only 2 FUH showed an FGFR3 mutation without deletions of chromosome 9. In
      contrast, 6 FUH revealed chromosome 9 deletions but wild type FGFR3 (p = 0.03).
      These results suggest that chromosome 9 deletions are the earliest genetic
      alterations in bladder cancer. The detection of FGFR3 mutations in FUH further
      supports the role of this lesion as precursor of papillary bladder cancer.

PMID- 16570287
TI  - iNOS-dependent DNA damage via NF-kappaB expression in hamsters infected with
      Opisthorchis viverrini and its suppression by the antihelminthic drug
      praziquantel.
AB  - Inflammation-mediated DNA damage triggered by Opisthorchis viverrini (OV)
      infection is a major risk factor of cholangiocarcinoma (CCA). We have recently
      reported that nitrative and oxidative DNA damage participates in CCA development
      caused by repeated infection with OV [Pinlaor et al., Carcinogenesis 2004;
      25:1535-42]. Therefore, to clarify the preventive effect of the antihelminthic
      drug praziquantel against cholangiocarcinogenesis, we assessed the effect of this
      drug on nitrative and oxidative DNA damage, including the formation of 8
      nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and the
      expression of inducible nitric oxide synthase (iNOS) by immunohistochemistry in
      OV-infected hamsters. We also examined the expression of nuclear factor-kappaB
      (NF-kappaB), which functions as a tumor promoter in inflammation-associated
      cancer. Our results showed that although 1-week treatment with praziquantel did
      not kill parasites completely in hamsters on days 14 and 30, this drug
      dramatically reduced inflammatory cell infiltration. Double immunofluorescence
      staining showed that drug treatment almost completely diminished OV-induced 8
      nitroguanine and 8-oxodG formation in bile duct epithelial cells. Quantitative
      analysis using an electrochemical detector coupled to HPLC revealed that 8-oxodG
      level in the liver of OV-infected hamsters was significantly decreased by drug
      treatment (p<0.05). Western blotting and immunohistochemistry revealed that the
      expression of NF-kappaB and iNOS in bile duct epithelium was reduced by drug
      treatment. The amount of nitrate plus nitrite in the liver and plasma was
      significantly decreased after drug treatment. It is concluded that praziquantel
      can exhibit a preventive effect against OV-induced cholangiocarcinoma by
      inhibiting iNOS-dependent DNA damage through not only elimination of parasites
      but also a potential antiinflammatory effect.

PMID- 16570288
TI  - SH-7, a new synthesized shikonin derivative, exerting its potent antitumor
      activities as a topoisomerase inhibitor.
AB  - 1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enylfuran-2
      caroxylate (SH-7), a new naphthoquinone compound, derived from shikonin,
      exhibited obvious inhibitory actions on topoisomerase II (Topo II) and
      topoisomerase I (Topo I), which were stronger than its mother compound shikonin.
      Notably, the SH-7's inhibitory potency on Topo II was much stronger than that on
      Topo I. In addition, SH-7 significantly stabilized Topo II-DNA cleavable complex
      and elevated the expression of phosphorylated-H2AX. The in vitro cell-based
      investigation demonstrated that SH-7 displayed wide cytotoxicity in diversified
      cancer cell lines with the mean IC(50) value of 7.75 microM. One important
      finding is SH-7 displayed significant cytotoxicity in the 3 MDR cell lines, with
      an average IC(50) value nearly equivalent to that of the corresponding parental
      cell lines. The average resistance factor (RF) of SH-7 was 1.74, which was much
      lower than those of reference drugs VP-16 (RF 145.92), ADR (RF 105.97) and VCR
      (RF 197.39). Further studies illustrated that SH-7 had the marked apoptosis
      inducing function on leukemia HL-60 cells, which was validated to be of
      mitochondria-dependence. The in vivo experiments showed that SH-7 had inhibitory
      effects on S-180 sarcoma implanted to mice, SMMC-7721, BEL-7402 human
      hepatocellular carcinoma and PC-3 human prostate cancer implanted to nude mice.
      Taken together, these results suggest that SH-7 induces DSBs as a Topo II
      inhibitor, which was crucial to activate the apoptotic process, and subsequently
      accounts for its both in vitro and in vivo antitumor activities. The well-defined
      Topo II inhibitory activity, antitumor effects particularly with its obvious anti
      MDR action, better solubility and less toxicity make SH-7 as a potential
      antitumor drug candidate for further research and development.

PMID- 16570289
TI  - Chromosome 5 imbalance mapping in breast tumors from BRCA1 and BRCA2 mutation
      carriers and sporadic breast tumors.
AB  - Comparative genomic hybridization (CGH) analysis has shown that chromosome 5q
      deletions are the most frequent aberration in breast tumors from BRCA1 mutation
      carriers. To map the location of putative 5q tumor suppressor gene(s), 26
      microsatellite markers covering chromosome 5 were used in loss of heterozygosity
      (LOH) analysis of breast tumors from BRCA1 (n = 42) and BRCA2 mutation carriers
      (n = 67), as well as in sporadic cases (n = 65). High-density array CGH was also
      used to map chromosome 5 imbalance in 10 BRCA1 tumors. A high LOH frequency was
      found in BRCA1 tumors (range 19-82%), as compared to BRCA2 and sporadic tumors
      (ranges 11-44% and 7-43%, respectively). In all, 11 distinct chromosome 5 regions
      with LOH were observed, the most frequent being 5q35.3 (82%), 5q14.2 (71%) and
      5q33.1 (69%) in BRCA1 tumors; 5q35.3 (44%), 5q31.3 (43%) and 5q13.3 (43%) in
      BRCA2 tumors and 5q31.3 (43%) in sporadic tumors. Array CGH analysis confirmed
      the very high frequency of 5q deletions, including candidate tumor suppressor
      genes such as XRCC4, RAD50, RASA1, APC and PPP2R2B. In addition, 2 distinct
      homozygous deletions were identified, spanning regions of 0.7-1.5 Mbp on 5q12.1
      and 5q12.3-q13.1, respectively. These regions include only a few genes, most
      notably BRCC3/DEPDC1B (pleckstrin/G protein interacting and RhoGAP domains) and
      PIK3R1 (PI3 kinase P85 regulatory subunit). Significant association (p < or =
      0.05) was found between LOH at certain 5q regions and factors of poor prognosis,
      including negative estrogen and progesterone receptor status, high grade, large
      tumor size and high portion of cells in S-phase. In conclusion, our results
      confirm a very high prevalence of chromosome 5q alterations in BRCA1 tumors,
      pinpointing new regions and genes that should be further investigated.

PMID- 16570290
TI  - Overexpression of RB1 transcript is significantly correlated with 13q14 allelic
      imbalance in colorectal carcinomas.
AB  - RB1 gene expression has been reported to be upregulated in colorectal carcinomas
      (CRC) at both the mRNA and protein levels when compared to normal colonic mucosa.
      However, allelic loss at the genomic level has been detected in CRC with widely
      differing frequencies ranging from 11.5% to 50%. To determine whether there is
      indeed a correlation between RB1 allelic imbalance (AI) and expression, a
      consecutive series of 55 CRC from Singapore patients were analysed by
      microsatellite analysis, real-time RT-PCR and immunohistochemistry.
      Microsatellite analysis using 3 RB1 intragenic microsatellite markers and 2
      markers flanking RB1 detected AI in 32.7% (18/55) of the cases, in at least 1
      locus. The highest AI frequency (22.9%) was observed at the microsatellite marker
      D13S137 (Cu13), which maps 5 cM distal to RB1. AI was present in both early and
      late Dukes stages. Real-time RT-PCR revealed that all 40 cases analysed expressed
      RB1 mRNA, with mRNA overexpression in 37.5% (15/40) and pRB protein expression in
      88.2% (30/34) of cases. Notably, a statistically significant correlation was
      found between AI of RB1 and mRNA overexpression of RB1 (p < 0.001, Fishers exact
      test). These findings provide evidence that despite AI, RB1 expression is not
      abrogated. Thus, our data suggests that RB1 may play a role in colorectal
      tumorigenesis through functional regulation of the transcript and protein rather
      than through its tumour suppressor role by gene inactivation.

PMID- 16570291
TI  - An unusual innervation of pectoralis minor and major muscles from a branch of the
      intercostobrachial nerve.
AB  - Variations of the branching pattern of the intercostobrachial nerve have been
      known to complicate dissection during mastectomy and other procedures involving
      the axilla. We present a unilateral case of a 73-year-old Caucasian female, in
      which the intercostobrachial nerve gives rise to an additional medial pectoral
      branch, which partially innervates the pectoralis minor muscle, as well as the
      abdominal head of pectoralis major muscle. Clinical consequences of such a
      variation may include motor losses, in addition to the commonly reported sensory
      losses, resulting from accidental or intentional dissection of the
      intercostobranchial nerve.

PMID- 16570292
TI  - The importance of structures adjacent to the first rib.

PMID- 16570293
TI  - From Ars to Scientia: the revolution of anatomic illustration.
AB  - Art and anatomy have been closely related since the Renaissance, when artists
      studied the human body to gain more perfect perspectives, and anatomists began
      illustrating their texts. As the two fields became increasingly intertwined, the
      distinctions between artistic drawings and scientific illustrations of the human
      body's form and function became increasingly blurred. Early Renaissance
      anatomists were more artistic than scientific with their images, but Hieronymus
      Fabricius ab Acquapendente (1533-1619) provided a crucial turning point in the
      evolution of anatomic illustration. His new and strict focus upon scientific
      illustration developed in the context of previous anatomists' work and theories,
      but his is a critical and previously untold story in the history of medicine.

PMID- 16570297
TI  - Oral methylphenidate fails to elicit significant changes in extracellular
      putaminal dopamine levels in Parkinson's disease patients: positron emission
      tomographic studies.
AB  - In this study, we assessed the changes of endogenous dopamine (DA) levels in
      response to methylphenidate in 5 patients with idiopathic Parkinson's disease
      (PD) and 6 healthy controls. Three-dimensional positron emission tomography was
      performed with the D2 receptor antagonist [11C]raclopride (RAC) at baseline and 1
      hour following the administration of oral methylphenidate (0.8 mg/kg) to assess
      changes in dopamine levels indirectly. Oral methylphenidate produced no
      significant change in extracellular DA levels in the putamen, as estimated by
      comparing changes in RAC binding at baseline and 1 hour following its
      administration in PD subjects and healthy controls. However, there were small
      changes in RAC binding of opposite direction in caudate and ventral striatal
      regions compared between the two groups. Although there was no consistent
      improvement in motor function in the PD group, some patients did experience a
      subjective high in response to methylphenidate (MP). Failure of oral MP to alter
      extracellular DA levels in putamen could result from degeneration of presynaptic
      dopaminergic terminals, with consequent severe reductions in the levels of
      endogenous DA and dopamine transporter in PD subjects. Our data provide in vivo
      neurochemical support for the lack of clinical efficacy following MP in PD
      patients and are also in keeping with reduced DA release following amphetamine in
      PD subjects.

PMID- 16570298
TI  - Pilot study of the incidence and prognosis of degenerative Parkinsonian disorders
      in Aberdeen, United Kingdom: methods and preliminary results.
AB  - The objective of this study was to test the methods for a large study of the
      incidence and prognosis of Parkinson's disease and other degenerative
      parkinsonian disorders and provide provisional incidence figures. This was a
      community-based prospective study to identify patients with newly diagnosed non
      drug-induced Parkinsonism (>or=2 of tremor, rigidity, bradykinesia, postural
      instability) from a population of 148,600 people in Aberdeen, Scotland, over 18
      months. Multiple search strategies were used to identify patients, including some
      population screening. Incident patients and age/sex-matched controls had
      assessments of impairment, disability, quality of life, mood, and cognition and
      are being followed up yearly. Two hundred and two people with possible
      parkinsonian symptoms were assessed, and 82 incident patients were identified, 50
      with probable Parkinson's disease. The crude incidences of probable Parkinsonism
      and probable Parkinson's disease were 31.4/100,000/year (95% CI: 24.5-39.7) and
      22.4/100,000/year (95% CI: 16.6-29.6), respectively. The mean age of diagnosis of
      Parkinson's disease was 76.1 +/- 10.0 years and the incidence was greater in men.
      The methods were generally successful. Provisionally, we found a higher incidence
      of Parkinson's disease than other comparable studies, and our patients were
      considerably older. This may reflect better case ascertainment in the elderly. A
      larger study is planned.

PMID- 16570299
TI  - Bladder dysfunction in Parkinsonism: mechanisms, prevalence, symptoms, and
      management.
AB  - The advent of functional imaging methods has increased our understanding of the
      neural control of the bladder. This review examines current concepts of the role
      of brain function in urinary control with particular emphasis on the putative
      role of dopamine receptors. Dopaminergic mechanisms play a profound role in
      normal bladder control and the dysfunction of these may result in symptoms of
      overactive bladder in Parkinsonism. The importance of this nonmotor disorder has
      been overlooked. We address the problem of bladder dysfunction as it presents to
      patients and their neurologist. The prevalence of bladder symptoms in Parkinson's
      disease is high; the most common complaint is nocturia followed by frequency and
      urgency. In multiple-system atrophy, the combination of urge and urge
      incontinence and poor emptying may result in a complex combination of complaints.
      The management of bladder dysfunction in Parkinsonism addresses treatment of
      overactive detrusor as well as incontinence.

PMID- 16570300
TI  - Diffusion-weighted imaging in Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative
      disorder that results from an expanded trinucleotide (CAG) repeat on the
      huntingtin gene. Neurodegeneration in HD affects most prominently the basal
      ganglia. Therefore, diffusivity was obtained in the basal ganglia and thalamus of
      29 patients with early HD and 27 healthy volunteers by means of the trace of the
      diffusion tensor (Trace(D)). Putaminal, caudate, pallidal, and thalamic Trace(D)
      values were increased in patients with HD compared with controls. Increased
      diffusivity in the putamen and caudate nucleus correlated with global functional
      impairment, CAG repeat length, as well as bicaudate ratio. Diffusion-weighted
      imaging appears to be a promising surrogate marker for disease severity in HD.
      Sensitivity to change remains to be established longitudinally.

PMID- 16570301
TI  - An open-label trial of levetiracetam for treatment of cervical dystonia.

PMID- 16570302
TI  - Development of a respirable, sustained release microcarrier for 5-fluorouracil I:
      In vitro assessment of liposomes, microspheres, and lipid coated nanoparticles.
AB  - The release rate of 5-fluorouracil (5-FU) from liposomes, microspheres, and lipid
      coated nanoparticles (LNPs) was determined by microdialysis to investigate their
      use as a respirable delivery system for adjuvant (postsurgery) therapy of lung
      cancer. 5-FU was incorporated into liposomes using thin film hydration and into
      microspheres and LNPs by spray drying. Primary particle size distributions were
      measured by dynamic light scattering. Liposomes released 5-FU in 4-10 h (k(1) =
      0.44-2.31/h, first-order release model). Extruded vesicles with diameters less
      than one micron released 5-FU more quickly than nonextruded vesicles. With poly
      (lactide) (PLA) and Poly-(lactide-co-glycolide) (PLGA) microspheres, slower
      release rates were observed (k(1) = 0.067-0.202/h). Increasing the
      lactide:glycolide ratio (50:50-100:0) resulted in a progressive decrease in the
      release rate of 5-FU. poly-(lactide-co-caprolactone) (PLCL) microspheres released
      5-FU more rapidly compared to PLGA systems (k(1) = 0.254-0.259/h). LNPs
      formulated with polymeric core excipients had lower release rates compared to
      monomeric excipients (k(1) = 0.043-0.105/h vs. k(1) = 0.192-0.345/h). Changing
      the lipid chain length of the shell lipid components had a relatively minor
      effect (k(1) = 0.043-0.129/h). Overall, these systems yielded a wide range of
      delivery durations that may be suitable for use as an inhalation delivery system
      for adjuvant therapy of lung cancer.

PMID- 16570303
TI  - Development of a respirable, sustained release microcarrier for 5-fluorouracil
      II: In vitro and in vivo optimization of lipid coated nanoparticles.
AB  - The release rate of 5-fluorouracil (5-FU) from lipid-coated nanoparticles (LNPs)
      was determined to develop a respirable delivery system for use as adjuvant
      (postsurgery) therapy for lung cancer. LNPs were prepared by spray drying, and
      the in vitro release was measured by microdialysis. The composition of the core
      and shell affected the release rate. Increasing the core diameter at constant
      shell thickness and increasing shell thickness at constant core diameter reduced
      the release rate, suggesting that the lipid shell is the rate limiting step for
      the release of 5-FU. A model consisting of a sequential zero-order/first-order
      dependence on time from polydispersed cores within polydispersed shells was
      developed to describe the release. Based on studies of the effect of geometry of
      the layered particles, the optimal formulation was identified as a 600-nm
      diameter 5-FU/poly-(glutamic acid) core with a 200-nm thick tripalmitin/cetyl
      alcohol shell. This system is readily aerosolized by ultrasonic atomization,
      which did not change the release properties. Preliminary instillation and
      inhalation delivery studies to the hamster resulted in lung levels of the
      particles and 5-FU that were near the desired values. Through this effort, a
      sustained-release, respirable delivery system for adjuvant therapy of lung cancer
      in humans may ultimately be realized.

PMID- 16570304
TI  - Thermodynamic stability and crystal structures for polymorphs and solvates of
      formoterol fumarate.
AB  - Polymorph screening of formoterol fumarate was performed in 12 solvents, followed
      by evaluations of thermodynamic stability. Three anhydrates, a dihydrate, a
      diethanolate, a diisopropanolate, and a dibensylalcoholate were found. The
      crystal structure of three solvated modifications and of the most stable
      anhydrate was investigated. This indicated that solvation is needed to get a
      stable and well packed crystal structure. Thermodynamic testing suggests that
      five crystal modifications are thermodynamically stable, at different conditions,
      since they are all reversibly related to each other.

PMID- 16570305
TI  - Structure and physical stability of hydrates and thermotropic mesophase of
      calcium benzoate.
AB  - The aim of this study is to investigate the hydration and the dehydration
      processes of calcium benzoate hydrates (trihydrate and monohydrate), thermotropic
      mesophases (dehydrated mesophase and lyophilized mesophase) and amorphous state,
      and the influence of their molecular order on those processes. X-ray analysis
      revealed that trihydrate has a planar structure composed of two types of planes
      one from benzoic acid, water, and calcium ion and another from benzoic acid and
      water-and that both planes are linked by three water molecules. It was found that
      calcium benzoate was able to exist as thermotropic mesophases by dehydration of
      trihydrate and lyophilization. These mesophases were characterized by polarizing
      light microscopy (PLM), X-ray powder diffraction (XRPD), differential thermal
      analysis (DTA), thermogravimetric analysis (TGA), and scanning electron
      microscopy (SEM). Both mesophases prepared by two procedures showed some similar
      physical properties, but lyophilized mesophase seemed to have molecular structure
      with higher order than dehydrated mesophase. The mesophases exhibited different
      hydration behavior. The dehydrated mesophase showed a stepwise rehydration
      process where it became monohydrate first and then trihydrate. The lyophilized
      mesophase became trihydrate without appearance of monohydrate. An amorphous form
      could also be prepared and it rehydrated first to the monohydrate and then
      trihydrate. The results suggest that the more disordered dehydrated mesophase and
      amorphous state change to monohydrate whereas the more ordered lyophilized
      mesophase cannot change to monohydrate but only to trihydrate.

PMID- 16570306
TI  - Thomas Hastie Bryce (1862-1946)--a lesson in the power of observation.
AB  - Thomas Hastie Bryce was Regius Professor of Anatomy at the University of Glasgow
      from 1909 to 1935. In Anatomy, he is remembered as an embryologist and as an
      editor of the 11th edition of Quain's Elements of Anatomy. His most-lasting
      scientific contribution, however, was in archaeology where he defined the Clyde
      Group of Neolithic cairns in south-west Scotland. He showed that the Neolithic
      people of Arran were of short stature and were dolichocephalic, distinct from
      those of the Bronze Age. Also, Bryce was the first to appreciate the importance
      of pottery in analyzing the movement of ancient peoples across Europe, and
      defined Beacharra ware, a class of Neolithic pottery unique to the west of
      Scotland. As in anatomy, archaeological discoveries are made by study of
      morphology and relationships with careful attention to detail and a sound
      knowledge of the literature.

PMID- 16570307
TI  - Polymorphism on leflunomide: stability and crystal structures.
AB  - Two polymorphs of Leflunomide were found and studied (form I and II). Both of
      them were characterized by X-ray powder diffraction and thermal analysis. Single
      crystals were obtained and both structures were solved. Forms I and II
      crystallize in the space group P2(1)/c with two and one independent molecules per
      asymmetric unit, respectively. Thermodynamic stability of the two forms is
      assessed by differential scanning calorimetry. The cohesion in the crystal of
      form I (the more stable) is provided by both by H bonding as well as pi...pi
      interactions, while in form II it is given only by the former. The independent
      molecules in form I adopt different conformations thus allowing for a larger
      number of intermolecular interactions.

PMID- 16570308
TI  - Clinical electrophysiological characterization of the acquired neuromyotonia
      phenotype of autoimmune peripheral nerve hyperexcitability.
AB  - Acquired autoimmune neuromyotonia is regarded as part of the spectrum of
      peripheral nerve hyperexcitability disorders. We aimed to use clinical
      neurophysiological measurements to study the extent, distribution, and
      characteristics of spontaneous motor unit potentials in 11 patients with acquired
      neuromyotonia. Investigations revealed that most spontaneous discharges recorded
      were motor unit, or partial motor unit potentials of normal size. Bursts of motor
      unit potentials arose more commonly from distal portions of the peripheral nerve
      and had abnormal absolute and relative refractory periods. Spontaneous discharges
      in some patients occurred in semirhythmic bursts in certain muscles. No patient
      had neurophysiological abnormalities detectable in first-order neurons of the
      central nervous system when using transcranial magnetic stimulation to estimate
      the threshold for corticomotor excitation and determine central motor conduction
      time. Only patients with coexistent myasthenia gravis had neurophysiologically
      detectable defects in neuromuscular transmission. The pathogenic region of
      abnormality in peripheral nerve hyperexcitability disorders therefore seems to
      lie within the terminal branches of peripheral motor nerves.

PMID- 16570309
TI  - Parallel, high-throughput purification of recombinant antibodies for in vivo cell
      assays.
AB  - We describe a method for high-throughput, parallel purification of secreted
      proteins to analyse large numbers of protein samples in cell-based assays for the
      discovery of protein therapeutics. The procedure is generic and capable of 96
      parallel purifications and compatible, in both yield and purity, with a wide
      assay range. By optimising expression and purification steps as well as using
      novel hardware, in particular a chromatography press capable to purify target
      proteins from viscous media, we exemplify the process for the generation of
      single-chain Fv antibody fragments (scFv) and the purification of full-length
      IgG. The described process can operate robustly with a throughput of over 2,000
      samples per month.

PMID- 16570310
TI  - Strategy for selection of methods for separation of bioparticles from particle
      mixtures.
AB  - The desired product of bioprocesses is often produced in particulate form, either
      as an inclusion body (IB) or as a crystal. Particle harvesting is then a crucial
      and attractive form of product recovery. Because the liquid phase often contains
      other bioparticles, such as cell debris, whole cells, particulate biocatalysts or
      particulate by-products, the recovery of product particles is a complex process.
      In most cases, the particulate product is purified using selective solubilization
      or extraction. However, if selective particle recovery is possible, the already
      high purity of the particles makes this downstream process more favorable. This
      work gives an overview of typical bioparticle mixtures that are encountered in
      industrial biotechnology and the various driving forces that may be used for
      particle-particle separation, such as the centrifugal force, the magnetic force,
      the electric force, and forces related to interfaces. By coupling these driving
      forces to the resisting forces, the limitations of using these driving forces
      with respect to particle size are calculated. It shows that centrifugation is not
      a general solution for particle-particle separation in biotechnology because the
      particle sizes of product and contaminating particles are often very small, thus,
      causing their settling velocities to be too low for efficient separation by
      centrifugation. Examples of such separation problems are the recovery of IBs or
      virus-like particles (VLPs) from (microbial) cell debris. In these cases,
      separation processes that use electrical forces or fluid-fluid interfaces show to
      have a large potential for particle-particle separation. These methods are not
      yet commonly applied for large-scale particle-particle separation in
      biotechnology and more research is required on the separation techniques and on
      particle characterization to facilitate successful application of these methods
      in industry.

PMID- 16570311
TI  - A long-term stable and adjustable osmotic pump for small volume flow based on
      principles of phloem loading.
AB  - An adjustable pump for microfluidics employing principles of osmoregulation
      analogous to those of phloem loading in plant leaves has been constructed and
      tested. Volume flow arises in a hollow fibre with vapour-permeable hydrophobic
      membrane. The fibre is connected to a source chamber filled with salt crystals
      and saturated salt solution. The source chamber takes up water through a
      relatively small membrane area and delivers saturated salt solution to one end of
      the capillary flow path within the hollow fibre. A stationary osmotic gradient is
      sustained in the hollow fibre lumen by constant input of saturated salt solution
      and radial osmotic water absorption. The strong temperature dependence of
      isothermal membrane distillation enables adjustment of the flow rate up to 20
      nL/s. The pump provides pulse-free flow of any liquid with constant rate for at
      least 26 days without recharging the source chamber. Backpressures up to 1 bar
      decrease the flow rate by less than 4%. The volume delivered at a constant rate
      is more than 40 times larger than the volume of the source chamber.
      Osmoregulatory pumps of the described type may be useful for microinfusion,
      microdialysis and analytical microsystems.

PMID- 16570312
TI  - Modeling the utilization of starch by activated sludge for simultaneous substrate
      storage and microbial growth.
AB  - This paper presents a mechanistic model incorporating microbial growth on
      external substrate with simultaneous formation of storage biopolymers (activated
      sludge model for growth and storage-ASMGS) for the utilization of starch by
      activated sludge. Model description and calibration utilized experimental data of
      an SBR fed with particulate native potato starch (NPS) and soluble starch (SolS)
      selected as model substrates. The fate of starch was monitored in a cycle
      together with glycogen and oxygen uptake rate (OUR) profiles. In the experiments,
      glycogen formation was significantly lower than predicted by total conversion of
      starch to glycogen, justifying the need to account for primary growth on starch.
      The proposed model basically modified Activated Sludge Model No.3 (ASM3), to
      include adsorption of starch, its hydrolysis and simultaneous growth and glycogen
      formation using the hydrolysis products, which was mainly maltose. Model
      simulations indicated hydrolysis of the adsorbed starch as the rate limiting
      process. The proposed model calibrated well the fate of all major model
      components, namely, starch, glycogen, and OUR. Particulate NPS and SolS were
      hydrolyzed with similar rates; however, primary and secondary growth processes on
      SolS were more efficient, with higher yields, due to the more easily utilizable
      products of SolS, both in terms of extracellular hydrolysis and of stored poly
      glucose. Modeling with ASM3, assuming starch as either readily or slowly
      biodegradable, did not provide an equally acceptable fit for the glycogen and OUR
      curves; supporting the need to consider primary growth together with storage as
      defined in the proposed model.

PMID- 16570313
TI  - Chromate reduction by immobilized palladized sulfate-reducing bacteria.
AB  - Resting cells of Desulfovibrio vulgaris NCIMB 8303 and Desulfovibrio
      desulfuricans NCIMB 8307 were used for the hydrogenase-mediated reduction of
      Pd(II) to Pd(0). The resulting hybrid palladium bionanocatalyst (Bio-Pd(0)) was
      used in the reduction of Cr(VI) to the less environmentally problematic Cr(III)
      species. The reduction of Cr(VI) by free and agar-immobilized Bio-Pd(0) was
      evaluated. Investigations using catalyst suspensions showed that Cr(VI) reduction
      was similar ( approximately 170 nmol Cr(VI)/h/mg Bio-Pd(0)) when Bio-Pd(0) was
      produced using D. vulgaris or D. desulfuricans. Continuous-flow studies using D.
      vulgaris Bio-Pd(0) with agar as the immobilization matrix investigated the effect
      of Bio-Pd(0) loading, inlet Cr(VI) concentration, and flow rate on the efficiency
      of Cr(VI) reduction. Reduction of Cr(VI) was highest at a D. vulgaris Bio-Pd(0)
      loading of 7.5 mg Bio-Pd(0)/mL agar (3:1 dry cell wt: Pd(0)), an input [Cr(VI)]
      of 100 microM, and a flow rate of 1.75 mL/h (approx. 3.5 column volumes/h). A
      mathematical interpretation predicted the activity of the immobilized Bio-Pd(0)
      for a given set of conditions within 5% of the value found by experiment.
      Considering the system as an 'artificial enzyme' analog and application of
      applied enzyme kinetics gave an apparent K(m) value (K(m app)) of 430 microM
      Cr(VI) and a determined value of flow-through reactor activity which differed by
      11% from that predicted mathematically.

PMID- 16570314
TI  - Transcriptional profiling of apoptotic pathways in batch and fed-batch CHO cell
      cultures.
AB  - Chinese Hamster ovary (CHO) cells are regarded as one of the "work-horses" for
      complex biotherapeutics production. In these processes, loss in culture viability
      occurs primarily via apoptosis, a genetically controlled form of cellular
      suicide. Using our "in-house" developed CHO cDNA array and a mouse
      oligonucleotide array for time profile expression analysis of batch and fed-batch
      CHO cell cultures, the genetic circuitry that regulates and executes apoptosis
      induction were examined. During periods of high viability, most pro-apoptotic
      genes were down-regulated but upon loss in viability, several early pro-apoptotic
      signaling genes were up-regulated. At later stages of viability loss, we detected
      late pro-apoptotic effector genes such as caspases and DNases being up-regulated.
      This sequential regulation of apoptotic genes showed that DNA microarrays could
      be used as a tool to study apoptosis. We found that in batch and fed-batch
      cultures, apoptosis signaling occurred primarily via death receptor- and
      mitochondria-mediated signaling pathways rather than endoplasmic reticulum
      mediated signaling. These insights provide a greater understanding of the
      regulatory circuitry of apoptosis during cell culture and allow for subsequent
      targeting of relevant apoptosis signaling genes to prolong cell culture.

PMID- 16570315
TI  - Intracellular ATP and total adenylate concentrations are critical predictors of
      reovirus productivity from Vero cells.
AB  - The productivity of reovirus type-3 Dearing was studied in cultures of Vero cells
      in serum-free media. Viral productivity was dependent upon the metabolic state of
      the cells rather than the phase of growth at which the cells were infected. Cells
      at different energy states were established by 24-h incubation in nutrient
      depleted media. This resulted in variable intracellular nucleotide concentrations
      but high cellular viability was maintained. Of the nucleotides analyzed at the
      time of infection only the intracellular [ATP] and total adenylate nucleotides
      were positively correlated with viral productivity. The correlated data followed
      a sigmoidal plot with an equation defined by polynomial regression analysis.
      Apparent threshold values of 3.2 fmol/cell and 3.3 fmol/cell were established for
      ATP and total adenylate, respectively, at which the viral production was 50% the
      maximal value. Cultures with lower ATP and total adenylate levels at the time of
      infection resulted in as much as a 95% reduction in overall viral titer compared
      to the control. The adenylate energy charge (AEC) showed a negative correlation
      with viral production with an AEC value >0.97 resulting in low virus
      productivity. Intracellular ATP or total adenylate concentration at the point of
      infection may be used as a predictor of viral yield in bioprocesses designed for
      virus/vaccine production.

PMID- 16570316
TI  - Disruption of Brewers' yeast by hydrodynamic cavitation: Process variables and
      their influence on selective release.
AB  - Intracellular products, not secreted from the microbial cell, are released by
      breaking the cell envelope consisting of cytoplasmic membrane and an outer cell
      wall. Hydrodynamic cavitation has been reported to cause microbial cell
      disruption. By manipulating the operating variables involved, a wide range of
      intensity of cavitation can be achieved resulting in a varying extent of
      disruption. The effect of the process variables including cavitation number,
      initial cell concentration of the suspension and the number of passes across the
      cavitation zone on the release of enzymes from various locations of the Brewers'
      yeast was studied. The release profile of the enzymes studied include alpha
      glucosidase (periplasmic), invertase (cell wall bound), alcohol dehydrogenase
      (ADH; cytoplasmic) and glucose-6-phosphate dehydrogenase (G6PDH; cytoplasmic). An
      optimum cavitation number Cv of 0.13 for maximum disruption was observed across
      the range Cv 0.09-0.99. The optimum cell concentration was found to be 0.5% (w/v,
      wet wt) when varying over the range 0.1%-5%. The sustained effect of cavitation
      on the yeast cell wall when re-circulating the suspension across the cavitation
      zone was found to release the cell wall bound enzyme invertase (86%) to a greater
      extent than the enzymes from other locations of the cell (e.g. periplasmic alpha
      glucosidase at 17%). Localised damage to the cell wall could be observed using
      transmission electron microscopy (TEM) of cells subjected to less intense
      cavitation conditions. Absence of the release of cytoplasmic enzymes to a
      significant extent, absence of micronisation as observed by TEM and presence of a
      lower number of proteins bands in the culture supernatant on SDS-PAGE analysis
      following hydrodynamic cavitation compared to disruption by high-pressure
      homogenisation confirmed the selective release offered by hydrodynamic
      cavitation.

PMID- 16570317
TI  - Engineering of Pichia pastoris for improved production of antibody fragments.
AB  - The methylotrophic yeast Pichia pastoris has been used for the expression of many
      proteins, including antibody fragments. However, limitations became obvious
      especially when secreting heterodimeric Fab fragments. Up-to-date, antibody
      fragments have only been expressed under control of the strong inducible alcohol
      oxidase 1 (AOX1) promoter, which may stress the cells by excessive transcription.
      Here, we examined the secretion characteristics of single chain and Fab fragments
      of two different monoclonal anti-HIV1 antibodies (2F5 and 2G12) with both the
      AOX1 and the glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter. Also, the
      influences of different secretion leaders and strains were evaluated.
      Interestingly, secretion was only achieved when using the GAP promoter and the
      Saccharomyces cerevisiae mating factor alpha (MFalpha leader), whereas there was
      no difference between the two P. pastoris strains. During fed batch fermentation
      of a 2F5 Fab expressing strain, intracellular retention of Fab heavy chains was
      observed, while both intact Fab and single light chain molecules were only
      detected in the supernatants. This led to the conclusion that protein folding and
      heterodimer assembly in the ER are rate limiting steps in Fab secretion. To
      alleviate this limitation, S. cerevisiae protein disulfide isomerase (PDI) and
      the unfolded protein response (UPR) transcription factor HAC1 were constitutively
      overexpressed in P. pastoris. While the overexpression of HAC1 led to a moderate
      increase of Fab secretion of 1.3-fold, PDI enabled an increase of the Fab level
      by 1.9-fold. Hence, the formation of interchain disulfide bonds can be seen as a
      major rate limiting factor to Fab assembly and subsequent secretion.

PMID- 16570318
TI  - Control of membrane-attached biofilms using surfactants.
AB  - The effect of surfactants on membrane-attached biofilms (MABs) was studied in a
      lab-scale extractive membrane bioreactor (EMB). Twenty-two surfactants were
      screened for their potential of increasing the cell wall negative charge (i.e.
      the electrostatic repulsion between bacteria) of Burkholderia sp. JS150 bacterial
      strain. Surfactants resulting in increased bacterial negative charge were further
      investigated for their effects on MAB population morphology and MAB attachment
      behaviour. Microscopic investigation of the bacterial population in MABs showed
      that surfactants affect the development of flagella, suggesting changes in the
      attachment capability of the JS150 strain in the presence of different
      surfactants. Among the screened surfactants, teepol showed the best
      characteristics in relation to the reduction of MAB accumulation, and it was
      tested in an EMB system for the extraction of monochlorobenzene from a synthetic
      wastewater. Comparison with a control EMB, operated without surfactants under the
      same conditions, proved that teepol effectively reduces MAB accumulation on the
      membrane walls. As a result, the overall mass transfer coefficient in the
      presence of teepol was 53% higher than in the control EMB.

PMID- 16570319
TI  - Simultaneous expression and maturation of the iron-sulfur protein ferredoxin in a
      cell-free system.
AB  - The model iron-sulfur (Fe-S) protein ferredoxin (Fd) from Synechocystis sp. PCC
      6803 has been simultaneously produced and matured in a cell-free production
      system. After 6 h of incubation at 37 degrees C, Fd accumulated to >450
      microg/mL. Essentially all was soluble, and 85% was active. Production and
      maturation of the protein in the cell-free system were found to be dependent in a
      coupled manner on the concentration of the supplemented iron and sulfur sources,
      ferrous ammonium sulfate and cysteine, respectively. The recombinant expression
      of ISC helper proteins during cell extract preparation did not increase cell-free
      Fd accumulation or activity, although the efficiency of iron and cysteine
      utilization increased. Fd maturation was independent of protein production rate,
      and proceeded at a constant rate throughout the period of active translation. In
      addition, incubation of denatured apo Fd with cell-free reaction components
      resulted in recovery of Fd activity, supporting the interpretation that
      maturation mechanisms did not act co-translationally. Incubation at 28 degrees C
      increased total and active protein accumulation, but decreased the ratio of
      active to total Fd produced. In summary, the high product yields and folding
      efficiency make the cell-free system described here an attractive platform for
      the study of Fe-S protein production and maturation. The system enables both
      small-volume, high throughput investigations as well as larger scale production.
      To our knowledge, this is the first demonstration of directed, high-yield
      production and maturation of an Fe-S protein in a cell-free system.

PMID- 16570320
TI  - Reactive oxygen species induced by shear stress mediate cell death in Bacillus
      subtilis.
AB  - Exposure of Bacillus subtilis to a shear rate of 1,482/s leads to a rapid loss of
      cell viability after 10 h of growth. Biochemical and molecular evidences provided
      below strongly suggest that cell death under high shear results from an apoptosis
      like process similar to that described in eukaryotes, with activation of a
      caspase-3-like protease (C(3)LP) followed by DNA fragmentation. Shear stress
      leads to an increase in specific intracellular reactive oxygen species (siROS),
      possibly through activation of NADH oxidase (NOX). The formation of siROS
      precedes the activation of C(3)LP and DNA fragmentation, thus establishing siROS
      as the molecular link between shear stress and apoptosis-like cell death. A model
      is proposed in which NOX is viewed as being strategically placed on the plasma
      membrane of B. subtilis that senses and converts a mechanical force arising from
      shear stress into a chemical signal leading to activation of C(3)LP, DNA
      fragmentation, and thus, apoptosis-like cell death.

PMID- 16570321
TI  - Kinetics and equilibria of lysozyme precipitation and crystallization in
      concentrated ammonium sulfate solutions.
AB  - The kinetics and thermodynamics of lysozyme precipitation in ammonium sulfate
      solutions at pH 4 and 8 and room temperature were studied. X-ray powder
      diffraction (XRD) was used to characterize the structure of lysozyme
      precipitates. It was found that, if sufficient time was allowed, microcrystals
      developed following an induction period after initial lysozyme precipitation,
      even up to ionic strengths of 8 m and at acidic pH, where lysozyme is refractory
      to crystallization in ammonium sulfate. The full set of precipitation and
      crystallization data allowed construction of a phase diagram of lysozyme, showing
      the ammonium sulfate dependence. It suggests that precipitation may reflect a
      frustrated metastable liquid-liquid phase separation, which would allow this
      process to be understood within the framework of the generic phase diagram for
      proteins. The results also demonstrate that XRD, more frequently used for
      characterizing inorganic and organic polycrystalline materials, is useful both in
      characterizing the presence of crystals in the dense phase and in verifying the
      crystal form of proteins.

PMID- 16570322
TI  - Kinetic modeling to optimize pentose fermentation in Zymomonas mobilis.
AB  - Zymomonas mobilis engineered to express four heterologous enzymes required for
      xylose utilization ferments xylose along with glucose. A network of pentose
      phosphate (PP) pathway enzymatic reactions interacting with the native glycolytic
      Entner Doudoroff (ED) pathway has been hypothesized. We have investigated this
      putative reaction network by developing a kinetic model incorporating all of the
      enzymatic reactions of the PP and ED pathways, including those catalyzed by the
      heterologous enzymes. Starting with the experimental literature on in vitro
      characterization of each enzymatic reaction, we have developed a kinetic model to
      enable dynamic simulation of intracellular metabolite concentrations along the
      network of interacting PP and ED metabolic pathways. This kinetic model is useful
      for performing in silico simulations to predict how varying the different enzyme
      concentrations will affect intracellular metabolite concentrations and ethanol
      production rate during continuous fermentation of glucose and xylose mixtures.
      Among the five enzymes whose concentrations were varied as inputs to the model,
      ethanol production in the continuous fermentor was optimized when xylose
      isomerase (XI) was present at the highest level, followed by transaldolase (TAL).
      Predictions of the model that the interconnecting enzyme phosphoglucose isomerase
      (PGI) does not need to be overexpressed were recently confirmed through
      experimental investigations. Through such systematic analysis, we can develop
      efficient strategies for maximizing the fermentation of both glucose and xylose,
      while minimizing the expression of heterologous enzymes.

PMID- 16570323
TI  - Biohydrogen production in granular up-flow anaerobic sludge blanket (UASB)
      reactors with mixed cultures under hyper-thermophilic temperature (70 degrees C).
AB  - Hyper-thermophilic hydrogen production without methane was demonstrated for the
      first time in granular up-flow anaerobic sludge blanket (UASB) system fed with
      glucose using mixed cultures. The maximum hydrogen yield in this study was 2.47
      +/- 0.15 mol H2/mol glucose. This high yield has never been previously reported
      in mixed culture systems and it was likely due to more favorable thermodynamic
      conditions at hyper-thermophilic temperatures. Different start-up strategies
      (bromoethanosulfonate (BES) addition and flow recycle) were evaluated. BES
      addition during start-up prevented the establishment of methanogenic cultures in
      granules. Flow recycle was important to achieve higher hydrogen yield through
      enriching better hydrogen-producing organisms and reduced the start-up period as
      well. This study indicated UASB system was a promising system for hydrogen
      production.

PMID- 16570324
TI  - Yeast prion-protein, sup35, fibril formation proceeds by addition and
      substraction of oligomers.
AB  - In analogy to human prions, a domain of the translation-termination protein in
      Saccharomyces cerevisiae, Sup35, can switch its conformation from a soluble
      functional state, [psi-], to a conformation, [PSI+], that facilitates aggregation
      and impairs its native function. Overexpression of the molecular chaperone Hsp104
      abolishes the [PSI+] phenotype and restores the normal function of Sup35. We have
      recently shown that Hsp104 interacts preferably with low oligomeric species of a
      Sup35 derived peptide, Sup35[5-26]; however, due to possible exchange between
      different oligomeric states, it was not possible to obtain information on the
      distribution and stability of the oligomeric state. We show here, that low
      molecular-weight oligomers (Sup35[5-26])n (n approximately = 4-6) are indeed
      important for the fibril formation and disassembly process. We find that Hsp104
      is able to disaggregate Sup35[5-26] fibrils by substraction of hexameric to
      decameric Sup35[5-26] oligomers. This disaggregation effect does not require
      assistance from other chaperones and is independent of ATP at high Hsp104
      concentrations. Furthermore, we demonstrate that critical oligomers have a
      preference for alpha-helical conformations. The conformational reorganization
      into beta-sheet structures seems to occur only upon incorporation of these
      oligomers into fibrillar structures. The results are demonstrated by using an
      equilibrium dialysis experiment that employed different molecular-weight cut-off
      membranes. A combination of thioflavin-T (ThT) fluorescence and UV measurements
      allowed the quantification of fibril formation and the amount of peptide
      diffusing out of the dialysis bag. CD and NMR spectroscopy data were combined to
      obtain structural information.

PMID- 16570325
TI  - Factorial structure of a short version of the Center for Epidemiologic Studies
      Depression Scale.
AB  - OBJECTIVE: To investigate the factor structure of a ten-item version of the
      Center for Epidemiologic Studies Depression Scale (CESD-10). METHOD: Two hundred
      and thirty-one Chinese persons aged 60-92 were individually interviewed with the
      CESD-10. The data were subject to confirmatory factor analysis testing several
      competing models. The one-factor model hypothesizes that all ten items are loaded
      on a single factor. In the two-factor model, positive affect items are loaded on
      one factor, and the remaining items on the other. The three-factor model
      distinguishes between positive affect, depressed affect, and somatic symptoms.
      RESULTS: The three-factor model was the best fitting model, with a comparative
      fit index of 0.95 and a standardized root mean square residual of 0.06. Depressed
      affect and somatic symptoms were highly correlated, and both were moderately
      correlated with positive affect. Nonetheless, all three factors appeared to tap a
      common underlying construct of depression-when a higher-order construct of
      depression was allowed to explain the intercorrelations of the three factors,
      depressed affect loaded at 0.88, somatic symptoms loaded at 0.92, and positive
      affect loaded at 0.51, on the higher-order construct. CONCLUSION: The data
      provided support for the factorial validity of the CESD-10.

PMID- 16570326
TI  - Musical hallucinations in psychiatric patients.

PMID- 16570327
TI  - Venlafaxine extended-release in patients older than 80 years with depressive
      syndrome.
AB  - OBJECTIVES: The aim of this evaluation was to assess the efficacy and safety of
      venlafaxine extended-release (ER) in very old primary care out-patients with
      depressive syndrome and associated anxiety symptoms. METHODS: This was an
      observational, naturalistic, multicenter, prospective, open-label study in an
      outpatient population with a diagnosis of depressive syndrome with anxiety
      symptoms. Minimum scores of 17 and 10 on the Hamilton Rating Scale for Depression
      (HAM-D(17)) and Anxiety (HAM-A), respectively, were required. Daily doses of 75
      mg to 225 mg of venlafaxine extended release (ER) were administered for 24 weeks.
      Effectiveness for depressive-anxious symptomatology was assessed using the HAM
      D(17) and HAM-A scales. PATIENTS: The 97 patients discussed in this report are a
      subgroup comprising all elderly patients, aged >or= 80 years, who were part of
      the larger observational, naturalistic, multicenter, prospective, open-label
      study and who had received venlafaxine ER for a maximum duration of 24 weeks.
      RESULTS: At endpoint, remission rates were 57.1% (HAM-D(17) <or=7), 66.2% (HAM-A
      <or= 7), and 52% (HAM-D(17) <or=7 and HAM-A <or= 7). Twenty patients (20.6%)
      dropped out or were withdrawn. Adverse events were reported by seven (7.2%)
      patients, none were reported as serious. CONCLUSIONS: Venlafaxine ER was shown to
      be an effective and safe drug for the treatment of very elderly primary care
      patients with depressive syndrome and associated anxiety symptoms.

PMID- 16570328
TI  - Cognitive impairment precipitated by air travel.

PMID- 16570329
TI  - Functional-group chemistry of organolithium compounds: photochemical [2+2]
      cycloaddition of alkenyl-substituted lithium cyclopentadienides.

PMID- 16570330
TI  - Practical synthesis of amides from in situ generated copper(I) acetylides and
      sulfonyl azides.

PMID- 16570331
TI  - Copper-catalyzed reaction cascade: direct conversion of alkynes into N
      sulfonylazetidin-2-imines.

PMID- 16570332
TI  - Multisegmented one-dimensional nanorods prepared by hard-template synthetic
      methods.
AB  - In the science and engineering communities, the nanoscience revolution is
      intensifying. As many types of nanomaterials are becoming more reliably
      synthesized, they are being used for novel applications in all branches of
      nanoscience and nanotechnology. Since it is sometimes desirable for single
      nanomaterials to perform multiple functions simultaneously, multicomponent
      nanomaterials, such as core-shell, alloyed, and striped nanoparticles, are being
      more extensively researched. Nanoscientists hope to design multicomponent
      nanostructures and exploit their inherent multiple functionalities for use in
      many novel applications. This review highlights recent advances in the synthesis
      of multisegmented one-dimensional nanorods and nanowires with metal,
      semiconductor, polymer, molecular, and even gapped components. It also discusses
      the applications of these multicomponent nanomaterials in magnetism, self
      assembly, electronics, biology, catalysis, and optics. Particular emphasis is
      placed on the new materials and devices achievable using these multicomponent,
      rather than single-component, nanowire structures.

PMID- 16570333
TI  - Experimental evidence from H/D exchange studies for the failure of direct C-C
      coupling mechanisms in the methanol-to-olefin process catalyzed by HSAPO-34.

PMID- 16570334
TI  - Intramolecular B-N coordination as a scaffold for electron-transporting
      materials: synthesis and properties of boryl-substituted thienylthiazoles.

PMID- 16570335
TI  - Precise facial control in threading guests into a molecular cage and the
      formation of a turtlelike supramolecular complex.

PMID- 16570336
TI  - A reaction-diffusion memory device.

PMID- 16570337
TI  - A metal-organic framework with a hierarchical system of pores and tetrahedral
      building blocks.

PMID- 16570338
TI  - A direct CO polymer electrolyte membrane fuel cell.

PMID- 16570341
TI  - Exacerbation of inflammatory bowel disease by nonsteroidal anti-inflammatory
      drugs and cyclooxygenase-2 inhibitors: fact or fiction?
AB  - The existence of a possible link between inflammatory bowel disease (IBD) and
      nonsteroidal anti-inflammatory drugs (NSAIDs) has been repeatedly suggested.
      Recently, a few studies have addressed the issue of a possible, similar effect by
      selective cyclooxygenase-2 inhibitors (COXIBs). The present article reviews the
      available scientific evidence for this controversial subject.

PMID- 16570340
TI  - Hepatobiliary and pancreatic disorders in celiac disease.
AB  - A variety of hepatic and biliary tract disorders may complicate the clinical
      course of celiac disease. Some of these have been hypothesized to share common
      genetic factors or have a common immunopathogenesis, such as primary biliary
      cirrhosis, primary sclerosing cholangitis and autoimmune forms of hepatitis or
      cholangitis. Other hepatic changes in celiac disease may be associated with
      malnutrition resulting from impaired nutrient absorption, including hepatic
      steatosis. In addition, celiac disease may be associated with rare hepatic
      complications, such as hepatic T-cell lymphoma. Finally, pancreatic exocrine
      function may be impaired in celiac disease and represent a cause of treatment
      failure.

PMID- 16570339
TI  - Gut flora and bacterial translocation in chronic liver disease.
AB  - Increasing evidence suggests that derangement of gut flora is of substantial
      clinical relevance to patients with cirrhosis. Intestinal bacterial overgrowth
      and increased bacterial translocation of gut flora from the intestinal lumen, in
      particular, predispose to an increased potential for bacterial infection in this
      group. Recent studies suggest that, in addition to their role in the pathogenesis
      of overt infective episodes and the clinical consequences of sepsis, gut flora
      contributes to the pro-inflammatory state of cirrhosis even in the absence of
      overt infection. Furthermore, manipulation of gut flora to augment the intestinal
      content of lactic acid-type bacteria at the expense of other gut flora species
      with more pathogenic potential may favourably influence liver function in
      cirrhotic patients. Here we review current concepts of the various inter
      relationships between gut flora, bacterial translocation, bacterial infection,
      pro-inflammatory cytokine production and liver function in this group.

PMID- 16570342
TI  - Role of radiation therapy in gastric adenocarcinoma.
AB  - Outcomes in patients with gastric cancer in the United States remain
      disappointing, with a five-year overall survival rate of approximately 23%. Given
      high rates of local-regional control following surgery, a strong rationale exists
      for the use of adjuvant radiation therapy. Randomized trials have shown superior
      local control with adjuvant radiotherapy and improved overall survival with
      adjuvant chemoradiation. The benefit of adjuvant chemoradiation in patients who
      have undergone D2 lymph node dissection by an experienced surgeon is not known,
      and the benefit of adjuvant radiation therapy in addition to adjuvant
      chemotherapy continues to be defined. In unresectable disease, chemoradiation
      allows long-term survival in a small number of patients and provides effective
      palliation. Most trials show a benefit to combined modality therapy compared to
      chemotherapy or radiation therapy alone. The use of pre-operative, intra
      operative, 3D conformal, and intensity modulated radiation therapy in gastric
      cancer is promising but requires further study. The current article reviews the
      role of radiation therapy in the treatment of resectable and unresectable gastric
      carcinoma, focusing on current recommendations in the United States.

PMID- 16570343
TI  - Pathogenesis of columnar-lined esophagus.
AB  - Since its initial description, the pathogenesis of the columnar-lined esophagus
      (CLE) has been surrounded by many controversies. The first controversy is related
      to the existence of the condition itself. The second controversy centers on
      whether the CLE is a congenital or an acquired condition. In this article, we
      review the congenital and acquired theories of development of CLE and discuss the
      various factors in acquisition of CLE. The bulk of evidence in the literature
      suggests that CLE is an acquired condition.

PMID- 16570344
TI  - Reduced expression of beta-catenin inhibitor Chibby in colon carcinoma cell
      lines.
AB  - AIM: To analyse the Chibby expression and its function in colon carcinoma cell
      lines and colorectal carcinoma (CRC). METHODS: Chibby expression levels were
      investigated by quantitative RT-PCR in a panel of seven different colon carcinoma
      cell lines. By sequencing, we analysed mutational status of Chibby. To test
      whether Chibby exhibited effects on beta-catenin signalling in colon carcinoma
      cells, we transfected SW480 cells with Chibby expression plasmid and,
      subsequently, analysed activity of beta-catenin and tested for alterations in
      cellular phenotype. In addition, we examined Chibby mRNA levels in samples of
      colorectal carcinomas and adjacent normal tissues by using quantitative RT-PCR
      and hybridised gene chips with samples from CRC and normal tissues. RESULTS:
      Chibby mRNA expression was strongly down-regulated in colon carcinoma cell lines
      in comparison to normal colon epithelial cells and no mutation in any of the
      examined colon carcinoma cell lines was found. Further, we could show that Chibby
      inhibited beta-catenin activity in TOPflash assays when over-expressed in SW480
      cells. Proliferation and invasion assays with Chibby transfected SW480 cells did
      not reveal profound differences compared to control cells. In contrast to these
      in vitro data, quantitative RT-PCR analyses of Chibby mRNA levels in CRC tumor
      samples did not show significant differences to specimens in adjacent non
      cancerous tissue. Consistent with these findings, gene chips analysing tissue
      samples of tumors and corresponding normal tissue did not show altered Chibby
      expression. CONCLUSION: Altered Chibby expression might be observed in vitro in
      different colon carcinoma cell lines. However, this finding could not be
      confirmed in vitro in CRC tumors, indicating that Chibby is not likely to promote
      CRC tumor development or progression. As Chibby is an important inhibitor of beta
      catenin signalling, our data implicate that the usability of colon carcinoma cell
      lines for in vitro studies analysing the Wnt/beta-catenin pathway in colorectal
      carcinoma needs extensive verification.

PMID- 16570345
TI  - Identification of serum proteins discriminating colorectal cancer patients and
      healthy controls using surface-enhanced laser desorption ionisation-time of
      flight mass spectrometry.
AB  - AIM: To detect the new serum biomarkers for colorectal cancer (CRC) by serum
      protein profiling with surface-enhanced laser desorption ionisation--time of
      flight mass spectrometry (SELDI-TOF MS). METHODS: Two independent serum sample
      sets were analysed separately with the ProteinChip technology (set A: 40 CRC+49
      healthy controls; set B: 37 CRC+31 healthy controls), using chips with a weak
      cation exchange moiety and buffer pH 5. Discriminative power of differentially
      expressed proteins was assessed with a classification tree algorithm.
      Sensitivities and specificities of the generated classification trees were
      obtained by blindly applying data from set A to the generated trees from set B
      and vice versa. CRC serum protein profiles were also compared with those from
      breast, ovarian, prostate, and non-small cell lung cancer. RESULTS: Mass-to
      charge ratios (m/z) 3.1x10(3), 3.3x10(3), 4.5x10(3), 6.6x10(3) and 28x10(3) were
      used as classifiers in the best-performing classification trees. Tree
      sensitivities and specificities were between 65% and 90%. Most of these
      discriminative m/z values were also different in the other tumour types
      investigated. M/z 3.3x10(3), main classifier in most trees, was a doubly charged
      form of the 6.6x10(3)-Da protein. The latter was identified as apolipoprotein C
      I. M/z 3.1x10(3) was identified as an N-terminal fragment of albumin, and m/z
      28x10(3) as apolipoprotein A-I. CONCLUSION: SELDI-TOF MS followed by
      classification tree pattern analysis is a suitable technique for finding new
      serum markers for CRC. Biomarkers can be identified and reproducibly detected in
      independent sample sets with high sensitivities and specificities. Although not
      specific for CRC, these biomarkers have a potential role in disease and treatment
      monitoring.

PMID- 16570346
TI  - Psychological impact of chronic hepatitis C: comparison with other stressful life
      events and chronic diseases.
AB  - AIM: To examine the psychological impact of chronic hepatitis C (CHC) diagnosis
      in a large cohort of CHC patients as compared with other stressful life events
      and chronic diseases carrying a risk of life-threatening complications. METHODS:
      One hundred and eighty-five outpatients with compensated CHC were asked to self
      grade, using a 100-mm visual analogue scale (VAS), the degree of stress caused by
      the learning of CHC diagnosis and the perceived severity of their disease.
      Diagnosis-related stress was compared to four other stressful life events and
      perceived CHC severity was compared to four other common chronic diseases.
      RESULTS: Learning of CHC diagnosis was considered a major stressful event (mean+/
      SD scores: 72+/-25), significantly less than death of a loved-one (89+/-13,
      P<0.0001) and divorce (78+/-23, P<0.007), but more than job dismissal (68+/-30,
      P<0.04) and home removal (26+/-24, P<0.0001). CHC was considered a severe disease
      (74+/-19), after AIDS (94+/-08, P<0.001) and cancer (91+/-11, P<0.001), but
      before diabetes (66+/-23, P<0.001) and hypertension (62+/-20, P<0.001). Perceived
      CHC severity was not related to the actual severity of liver disease, assessed
      according to Metavir fibrosis score. In multivariate analysis, diagnosis-related
      stress was related to perceived disease severity (P<0.001), trait anxiety
      (P<0.001) and infection through blood transfusion (P<0.001). CONCLUSION: Our
      results show the considerable psychological and emotional burden that a diagnosis
      of CHC represents, even in the absence of significant liver disease. They should
      be taken into account when announcing a diagnosis of CHC in order to reduce its
      negative effects.

PMID- 16570347
TI  - Efficient expression of histidine-tagged large hepatitis delta antigen in
      baculovirus-transduced baby hamster kidney cells.
AB  - AIM: To study the baculovirus/mammalian cell system for efficient expression of
      functional large hepatitis delta antigen (L-HDAg). METHODS: A recombinant
      baculovirus expressing histidine-tagged L-HDAg (L-HDAgH) was constructed to
      transduce baby hamster kidney (BHK) cells by a simplified transduction protocol.
      RESULTS: The recombinant baculovirus transduced BHK cells with efficiencies
      higher than 90% as determined by flow cytometry. The expression level was
      significantly higher than that obtained by plasmid transfection and was further
      enhanced 3-fold to around 19 pg/cell by the addition of 10 mmol/L sodium
      butyrate. Importantly, the expressed L-HDAgH was localized to the cell nucleus
      and correctly isoprenylated as determined by immunofluorescence labeling and
      confocal microscopy. Moreover, L-HDAgH interacted with hepatitis B surface
      antigen to form virus-like particles. CONCLUSION: The fusion with histidine tags
      as well as overexpression of L-HDAgH in the baculovirus-transduced BHK cells does
      not impair the biological functions. Taken together, the baculovirus/mammalian
      cell system offers an attractive alternative for high level expression of L-HDAgH
      or other proteins that require extensive post-translational modifications.

PMID- 16570348
TI  - Relaxin prevents the development of severe acute pancreatitis.
AB  - AIM: To investigate the severity of acute pancreatitis (AP) is associated to the
      intensity of leukocyte activation, inflammatory up-regulation and
      microcirculatory disruption associated to ischemia-reperfusion injury.
      Microvascular integrity and inhibition of pro-inflammatory mediators are key
      factors in the evolution of AP. Relaxin is an insulin-like hormone that has been
      attributed vasorelaxant properties via the nitric oxide pathway while behaving as
      a glucocorticoid receptor agonist. METHODS: AP was induced by the bilio
      pancreatic duct-outlet-exclusion closed-duodenal-loops model. Treatment with
      relaxin was done at different time-points. Nitric oxide synthase inhibition by L
      NAME and glucocorticoid receptor (GR) blockage by mifepristone was considered. AP
      severity was assessed by biochemical and histopathological analyses. RESULTS:
      Treatment with relaxin reduced serum amylase, lipase, C-reactive protein, IL-6,
      IL-10, hsp72, LDH and 8-isoprostane as well as pancreatic and lung
      myeloperoxidase. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate
      were also decreased. ATP depletion and ADP/ATP ratio were reduced while caspases
      2-3-8 and 9 activities were increased. L-NAME and mifepristone decreased the
      efficiency of relaxin. CONCLUSION: Relaxin resulted beneficial in the treatment
      of AP combining the properties of a GR agonist while preserving the
      microcirculation and favoring apoptosis over necrosis.

PMID- 16570349
TI  - Cis-hydroxyproline-induced inhibition of pancreatic cancer cell growth is
      mediated by endoplasmic reticulum stress.
AB  - AIM: To investigate the biological effects of cis-hydroxyproline (CHP) on the rat
      pancreatic carcinoma cell line DSL6A, and to examine the underlying molecular
      mechanisms. METHODS: The effect of CHP on DSL6A cell proliferation was assessed
      by using BrdU incorporation. The expression of focal adhesion kinase (FAK) was
      characterized by Western blotting and immunofluorescence. Induction of
      endoplasmic reticulum (ER) stress was investigated by using RT-PCR and Western
      blotting for the glucose-related protein-78 (GRP78) and growth arrest and DNA
      inducible gene (GADD153). Cell viability was determined through measuring the
      metabolic activity based on the reduction potential of DSL6A cells. Apoptosis was
      analyzed by detection of caspase-3 activation and cleavage of poly(ADP-ribose)
      polymerase (PARP) as well as DNA laddering. RESULTS: In addition to inhibition of
      proliferation, incubation with CHP induced proteolytic cleavage of FAK and a
      delocalisation of the enzyme from focal adhesions, followed by a loss of cell
      adherence. Simultaneously, we could show an increased expression of GRP78 and
      GADD153, indicating a CHP-mediated activation of the ER stress cascade in the
      DSL6A cell line. Prolonged incubation of DSL6A cells with CHP finally resulted in
      apoptotic cell death. Beside L-proline, the inhibition of intracellular
      proteolysis by addition of a broad spectrum protease inhibitor could abolish the
      effects of CHP on cellular functions and the molecular processes. In contrast,
      impeding the activity of apoptosis-executing caspases had no influence on CHP
      mediated cell damage. CONCLUSION: Our data suggest that the initiation of ER
      stress machinery by CHP leads to an activation of intracellular proteolytic
      processes, including caspase-independent FAK degradation, resulting in damaging
      pancreatic carcinoma cells.

PMID- 16570350
TI  - Expression and location of Smad2, 4 mRNAs during and after liver fibrogenesis of
      rats.
AB  - AIM: To investigate the location alteration of Smad2 and Smad4 mRNAs in the liver
      during and after fibrogenesis in rats. METHODS: Eighty male Wistar rats weighing
      approximately 200 g each were used. The rat models of experimental hepatic
      fibrosis were established by injection with carbon tetrachloride (CCl4), normal
      rats and rats were injected with olive oil and served as control groups. In situ
      hybridization(ISH) was used to detect the Smad2 and Smad4 mRNA in liver. RESULTS:
      In situ hybridization showed Smad2 and Smad4 mRNA expressions in the cytoplasm of
      hepatic stellate cells (HSC), fibroblasts and myofibroblasts around the central
      vein and hepatic sinus during and after fibrogenesis. Expression of Smad2, 4 mRNA
      was higher than that in normal and control rats. CONCLUSION: In the process of
      and after hepatic fibrosis formation, HSC, fibroblasts and myofibroblasts are the
      major cells that express Smad2 and Smad4. The more serious the hepatic fibrosis
      is in the injured liver, the higher the level of Smad2 and Smad4 gene expression
      is during and after fibrogenesis respectively.

PMID- 16570351
TI  - Expression of c-kit receptor in human cholangiocarcinoma and in vivo treatment
      with imatinib mesilate in chimeric mice.
AB  - AIM: To investigate the c-kit expression in biliary tract cancer cell lines and
      histological sections from patients with extrahepatic cholangiocarcinoma (CC) and
      to evaluate the efficacy of in vitro and in vitro treatment with imatinib
      mesilate. METHODS: The protein expression of c-kit in the human biliary tract
      cancer cell lines Mz-ChA-2 and EGI-1 and histological sections from 19 patients
      with extrahepatic CC was assessed by immunoblotting, immunocytochemistry, and
      immunohistochemistry. The anti-proliferative effect of imatinib mesilate on
      biliary tract cancer cell lines Mz-ChA-2 and EGI-1 was studied in vitro by
      automated cell counting. In addition, immunodeficient NMRI mice (Taconic) were
      subcutaneously injected with 5x10(6) cells of cell lines MzChA-2 and EGI-1. After
      having reached a tumour volume of 200 mm3, daily treatment was started
      intraperitoneally with imatinib mesilate at a dose of 50 mg/kg or normal saline
      (NS). Tumor volume was calculated with a Vernier caliper. After 14 d, mice were
      sacrificed with tumors excised and tumor mass determined. RESULTS: Immunoblotting
      revealed presence of c-kit in Mz-ChA-2 and absence in EGI-1 cells.
      Immunocytochemistry with c-kit antibodies displayed a cytoplasmatic and
      membraneous localization of receptor protein in Mz-ChA-2 cells and absence of c
      kit in EGI-1 cells. c-kit was expressed in 7 of 19 (37%) extrahepatic human CC
      tissue samples, 2 showed a moderate and 5 a rather weak immunostaining. Imatinib
      mesilate at a low concentration of 5 micromol/L caused a significant growth
      inhibition in the c-kit positive cell line Mz-ChA-2 (31%), but not in the c-kit
      negative cell line EGI-1 (0%) (P<0.05). Imatinib mesilate at an intermediate
      concentration of 10 micromol/L inhibited cellular growth of both cell lines (51%
      vs 57%). Imatinib mesilate at a higher concentration of 20 micromol/L seemed to
      have a general toxic effect on both cell lines. The IC50 values were 9.7
      micromol/L and 11 micromol/L, respectively. After 14 d of in vitro treatment with
      imatinib mesilate, using the chimeric mouse model, c-kit positive Mz-ChA-2 tumors
      had a significantly reduced volume and mass as compared to NS treatment (P<0.05).
      In contrast to that, treatment of mice bearing c-kit negative EGI-1 tumors did
      not result in any change of tumor volume and mass as compared to NS treatment.
      CONCLUSION: c-kit expression is detectable at a moderate to low protein level in
      biliary tract cancer. Imatinib mesilate exerts marked effects on tumor growth in
      vitro and in vitro dependent on the level of c-kit expression.

PMID- 16570352
TI  - Effect of 5-HT1 agonist (sumatriptan) on anorectal function in irritable bowel
      syndrome patients.
AB  - AIM: To evaluate the effect of sumatriptan, a selective 5-HT1 agonist, on
      anorectal function in irritable bowel syndrome (IBS) patients. METHODS: Twenty
      two IBS patients selected according to the Rome II criteria (F 15, M 7; mean age
      29.3+/-6.8, range 22-44 years) were examined. The study was blind, randomized and
      placebo-controlled with a crossover design. Anorectal manometry and rectal
      balloon distension test were performed before and after the administration of
      placebo and sumatriptan. RESULTS: The administration of sumatriptan caused a
      significant increase in the resting anal canal pressure from 9.2+/-2.0 kPa to
      13.1+/-3.3 kPa (P<0.0001) connected with the increase in the anal sphincter
      length and high pressure zone. After sumatriptan injection a remarkable increase
      in the threshold for the first sensation from 27+/-9 mL to 34+/-12 mL (P<0.05)
      and urge sensation from 61+/-19 mL to 68+/-18 mL (P<0.01) was observed.
      Sumatriptan did not affect either the volume evoking the rectoanal inhibitory
      reflex or the results of the straining test. CONCLUSION: 5-HT1 receptors
      participate in the regulation of anorectal function. Elucidation of the role of 5
      HT1 receptors in the pathophysiological mechanisms of IBS may have some
      therapeutic implications.

PMID- 16570353
TI  - Effect of gemcitabine on the expression of apoptosis-related genes in human
      pancreatic cancer cells.
AB  - AIM: To investigate the expression of genes involved in the gemcitabine-induced
      cytotoxicity in human pancreatic cancer cells. METHODS: A human pancreatic cancer
      cell line, PANC-1, was cultured. 1x10(4) PANC-1 cells were plated in 96-well
      microtiter plates. After being incubated for 24 h, gemcitabine was added to the
      medium at concentrations ranging 2.5-1000 mg/L. The AlamarBlue dye method was
      used for cell growth analysis. DNA fragmentation was quantitatively assayed using
      a DNA fragmentation enzyme-linked immunosorbent assay (ELISA) kit. PAP and
      TP53INP1 mRNA expression was determined using the reverse transcription
      polymerase chain reaction with semi-quantitative analysis. The expression of GSK
      3beta and phospho-GSK-3beta proteins was examined with Western blot analysis.
      RESULTS: The IC50 for the drug after a 48-h exposure to gemcitabine was 16 mg/L.
      The growth of PANC-1 cells was inhibited by gemcitabine in a concentration
      dependent manner (P<0.0001) and the cell growth was also inhibited throughout the
      time course (P<0.0001). The DNA fragmentation rate in the gemcitabine-treated
      group at 48 h was 44.7%, whereas it was 25.3% in the untreated group. The PAP
      mRNA expression was decreased after being treated with gemcitabine, whereas the
      TP53INP1 mRNA was increased by the gemcitabine treatment. Western blot analysis
      showed that phospho- GSK-3beta (ser9) was induced by the gemcitabine treatment.
      CONCLUSION: Gemcitabine suppresses PANC-1 cell proliferation and induces
      apoptosis. Apoptosis is considered to be associated with the inhibition of PAP
      and GSK-3beta, and the activation of TP53INP1 and pospho-GSK-3beta (ser9).

PMID- 16570354
TI  - Mangafodipir trisodium-enhanced magnetic resonance imaging for evaluation of
      pancreatic mass and mass-like lesions.
AB  - AIM: To investigate the role of mangafodipir trisodium (MnDPDP) in focal
      pancreatic masses and mass-like lesions by evaluating contrast uptake features of
      the lesions and pancreatic parenchyma after contrast medium injection. METHODS: A
      total of 37 patients with pancreatic mass or mass-like lesions were examined by
      unenhanced and MnDPDP-enhanced magnetic resonance imaging (MRI). RESULTS: MRI was
      obtained 20-40 min after infusion of MnDPDP and homogeneous contrast enhancement
      was observed in normal pancreas parenchyma. In patients with atrophic pancreas
      there was no enhancement in pancreatic parenchyma on MnDPDP-enhanced MRI. In 37
      patients with 41 pancreatic masses and mass-like lesions, contrast enhancement
      was observed at 5 lesions on MnDPDP enhanced MRI. Three of these 5 lesions were
      focal pancreatitis and the other 2 were adenocarcinoma. No contrast enhancement
      was determined in 36 pancreatic masses and mass-like lesions in 32 patients.
      CONCLUSION: MnDPDP contrast-enhanced MRI, especially in cases with no parenchyma
      atrophy, can distinguish focal pancreatic lesion margins. Information about the
      function of pancreatic parenchyma can be obtained out of tumor. MnDPDP
      facilitates staging of pancreatic tumors by detection of metastatic lesions in
      the liver. In addition, diminished heteregenous uptake of MnDPDP in patients with
      pancreatitis may be helpful in differential diagnosis.

PMID- 16570356
TI  - Soluble CD40 ligand in prediction of acute severe pancreatitis.
AB  - AIM: To assess the early predictability of the soluble CD40L (sCD40L) in
      pancreatitis severity. METHODS: Between February 2000 and February 2003, 279
      consecutive patients with acute pancreatitis were prospectively enrolled in our
      study. In this report, 40 patients with mild and 40 patients with severe
      pancreatitis were randomly studied. sCD40L concentrations were measured 48 hours
      after admission. RESULTS: sCD40L levels were significantly higher 48 hours after
      admission in severe pancreatitis than in mild pancreatitis. Using a cutoff of
      1000 pg/L, the sensitivity and specificity of sCD40L to detect a severe course of
      the disease were 78% and 62% respectively compared to 72% and 81% for CRP.
      Logistic regression analysis found that CRP was the only statistically
      significant marker able to detect a severe course of the disease. CONCLUSION:
      These findings indicate that CRP remains a valuable marker to determine the
      severity and prognosis of acute pancreatitis whereas sCD40L levels should be
      assessed in further studies.

PMID- 16570355
TI  - Hyperhomocysteinemia and hypercoagulability in primary biliary cirrhosis.
AB  - AIM: To assess the hypercoagulability in PBC and its relationship with
      homocysteine (HCY) and various components of the haemostatic system. METHODS: We
      investigated 51 PBC patients (43F/8M; mean age: 63+/-13.9 yr) and 102 healthy
      subjects (86 women/16 men; 63+/-13 yr), and evaluated the haemostatic process in
      whole blood by the Sonoclot analysis and the platelet function by PFA-100 device.
      We then measured HCY (fasting and after methionine loading), tissue factor (TF),
      thrombin-antithrombin complexes (TAT), D-dimer (D-D), thrombomodulin (TM), folic
      acid, vitamin B6 and B12 plasma levels. C677T 5,10-methylenetetrahydrofolate
      reductase (MTHFR) polymorphism was analyzed. RESULTS: Sonoclot RATE values of
      patients were significantly (P<0.001) higher than those of controls. Sonoclot
      time to peak values and PFA-100 closure times were comparable in patients and
      controls. TAT, TF and HCY levels, both in the fasting and post-methionine
      loading, were significantly (P<0.001) higher in patients than in controls.
      Vitamin deficiencies were detected in 45/51 patients (88.2%). The prevalence of
      the homozygous TT677 MTHFR genotype was significantly higher in patients (31.4%)
      than in controls (17.5%) (P<0.05). Sonoclot RATE values correlated significantly
      with HCY levels and TF. CONCLUSION: In PBC, hyper-HCY is related to
      hypovitaminosis and genetic predisposing factors. Increased TF and HCY levels and
      signs of endothelial activation are associated with hypercoagulability and may
      have an important role in blood clotting activation.

PMID- 16570357
TI  - Association of the HLA-DRB1*0701 allele with perinuclear anti-neutrophil
      cytoplasmatic antibodies in Mexican patients with severe ulcerative colitis.
AB  - AIM: To determine the association between the HLA-DRB1 alleles and perinuclear
      anti-neutrophil cytoplasmatic antibodies (p-ANCA) positive in Mexican patients
      with ulcerative colitis (UC). METHODS: Ninety Mexican mestizo patients (45
      females) with UC, confirmed by biopsy, were studied. High resolution HLA typing
      was performed by PCR-SSO reverse dot blot and PCR-SSP. Molecular typing
      techniques were applied to define HLA-DRB1 alleles. Enzyme-linked immunosorbent
      assay and immunofluorescence techniques were used to detect p-ANCA. RESULTS:
      Forty-eight (53%) UC patients were positive for p-ANCA by ELISA and IF. We found
      that p-ANCA-positive UC patients had a significantly increased frequency of HLA
      DR7 compared with p-ANCA-negative controls (22% vs 5.1%; pC=0.02, OR=5.2, CI 95%:
      1.06-37.82). Disease activity was scored as severe in 20 patients, moderate in 8,
      mild in 14 and no activity in the remaining 38 patients according to the Truelove
      and Witts criteria. Subgroup analysis showed a significantly increased frequency
      of the HLA-DRB1*07 allele in 15 of 20 UC patients with severe activity of UC and
      p-ANCA positivity [100% vs 0%; pC=0.0000001; OR=35]. No significant differences
      were found between p-ANCA positive patients, HLA-DR alleles and other clinical
      features such as extraintestinal manifestations, proctocolectomy and extension.
      CONCLUSION: The HLA-DRB1*07 is associated with p-ANCA positive UC Mexican
      patients.

PMID- 16570358
TI  - Elevated plasma cryofibrinogen in patients with active inflammatory bowel disease
      is morbigenous.
AB  - AIM: To investigate the role of cryofibrinogen (CF) in active inflammatory bowel
      disease (IBD). METHODS: CF was assayed in 284 subjects: 61 with active and 63
      with inactive ulcerative colitis (UC), 45 who had proctocolectomy, 35 with active
      and 20 with inactive Crohn's disease (CD), 40 with other diseases and 20 healthy
      controls. Trypsin inhibitor (TI) and TI antibody (TI-Ab) were measured in plasma
      and CF complex by ELISA. RESULTS: CF in active UC was strikingly high compared
      with all other groups (c2<0.001). Similarly, CF was significantly higher in
      active CD than in inactive CD or in controls (c2<0.01). In UC, high CF and TI-Ab
      were associated with the need for operations. Further, high CF, CF/fibrinogen
      ratio, low TI and high TI-Ab in plasma were associated with disease activity or
      refractoriness to medication. Elevated CF was not associated with acute reactants
      like C-reactive protein and white blood cell counts except for erythrocyte
      sedimentation rate, suggesting that elevated CF was not a consequence of acute
      inflammation. CONCLUSION: Elevated CF in active IBD appears to be morbigenous. CF
      promotes IBD via two main mechanisms, quenching of TI (an anti-inflammatory
      substance) and impairing microvascular perfusion by forming protein aggregates.
      CF may also serve as a biomarker of chronic IBD. Additional studies are warranted
      to fully evaluate the role of CF in IBD and the outcome should contribute to a
      better understanding of the pathogenesis of IBD.

PMID- 16570359
TI  - Using p53-immunostained large specimens to determine the distal intramural spread
      margin of rectal cancer.
AB  - AIM: To determine the distal intramural spread (DIS) margin of rectal cancer.
      METHODS: Sixty-one p53-positive specimens of rectal cancer were used. After
      conventional hematoxylin and eosin (H&E) staining, the DIS margin of rectal
      cancer in large specimens was examined by immunohistochemistry. The patients were
      divided into A, B, C, and D groups. After a long-term follow-up, the survival
      curves of the four groups were estimated using the life table. RESULTS: Fifty-one
      of the sixty-one cases (83.6%) had DIS. The extent of DIS ranged 0.11-3.5 cm;
      meanwhile the mean of DIS measured by H&E staining was 0.13 cm. The significant
      difference was found between the means (t=5.622, P<0.0001). Only 1 of 51 patients
      had DIS greater than 3 cm. The DIS was less than 1.0 cm in most rectal cancer
      patients. The long-term results indicated that the survival rate of the patients
      whose DIS was greater than 1.0 cm was lower than that of the patients whose DIS
      was less than 0.5 cm. CONCLUSION: Rectal cancer patients with DIS greater than
      1.0 cm have poor prognosis.

PMID- 16570360
TI  - Duodenal duplication cyst causing severe pancreatitis: imaging findings and
      pathological correlation.
AB  - We here report a case of a 18-year-old man with a history of recurrent abdominal
      pain and a previous episode of severe acute pancreatitis. Abdominal
      ultrasonography, contrast enhanced multislice computer tomography, endoscopic
      retrograde cholangiopancreatography, endoscopic ultrasonography and magnetic
      resonance imaging demonstrated a cystic mass lesion. Only on delayed phase
      magnetic resonance images after Gadolinium-BOPTA injection, it was possible to
      demonstrate the lesionos relationship with the biliary tree, differentiating the
      lesion from intraluminal duodenal diverticulum, and to achieve the diagnosis of
      duodenal duplication cyst, a recognized rare cause of acute pancreatitis. The
      diagnosis was confirmed by histology.

PMID- 16570362
TI  - Uveitis in autoimmune hepatitis: a case report.
AB  - In this case report we describe for the first time an association between
      autoimmune hepatitis (AIH) and uveitis, without any doubts about other possible
      etiologies, such as HCV, since all the old reports describe the association of
      AIH with iridocyclitis before tests for HCV-related hepatitis could be available.
      A 38-year-old businessman with abnormal liver function tests and hyperemia of the
      bulbar conjunctiva was admitted to the hospital. Six years before admission, the
      patient presented with persistent fever, arthralgias, conjunctival hyperemia,
      leukocytosis and increased ESR, referred to acute rheumatic fever. The presence
      of systemic diseases, most commonly associated with uveitis, was investigated
      without results and the patient was then treated with topical corticosteroids.
      His symptoms resolved. A test for anti-nuclear antibodies was positive, at a
      titre of 1:320, with a speckled and nucleolar staining pattern. Liver ultrasound
      showed mild hepatomegaly with an increased echostructure of the liver.
      Percutaneous liver biopsy was performed under ultrasound assistance. Histological
      examination showed necroinflammation over the portal, periportal and lobular
      areas, fibrotic portal tracts, with periportal fibrosis and occasional portal-to
      portal bridgings, but intact hepatic architecture. Some hepatocytes showed barely
      discernible granules of hemosiderin in the lobular area. Bile ductules had not
      any significant morphological alterations. METAVIR score was A2-F3, according to
      the modified HAI grading/fibrosis staging. The patient was diagnosed to have AIH
      with mild activity and fibrosis and was discharged on 25 mg prednisone, entering
      clinical and biochemical remission, further confirming diagnosis. After discharge
      the patient continued to have treatment with corticosteroids as an outpatient at
      a dose of 5 mg. On January 2002 the patient was readmitted to the hospital. A
      test for anti-nuclear antibodies was positive, at a titre of 1:320, with a
      speckled and nucleolar staining pattern. Anti-smooth muscle antibody test was
      also positive (1:160), while anti-LKM antibodies were negative. Ophthalmologic
      examination revealed inflammatory cells and proteinaceous flare in the anterior
      chamber of the left eye, and a stromal lesion in the cornea. He was maintained on
      immunosuppressive therapy (5 mg prednisone plus topical antibiotic therapy for
      two weeks) and then discharged. A complete remission of the symptoms was
      registered on follow-up. At present (July 2005), the patient is on prednisone (5
      mg) and has no symptoms. Liver function tests are also within the normal range.

PMID- 16570361
TI  - Jumbo biopsy is useful for the diagnosis of colonic prolapsing mucosal polyps
      with diverticulosis.
AB  - We report here a case of multiple prolapsing mucosal polyps with diverticulosis
      in the sigmoid colon. A 52-year-old man was admitted to our hospital because of
      bloody diarrhea. Colonoscopy and barium enema showed multiple diverticula,
      markedly thickened mucosal folds and polypoid lesions with mucus on the top of
      them in the sigmoid colon. Endoscopic ultrasonography showed thickening of the
      mucosal and submucosal layers. Several endoscopic biopsy specimens were taken
      from the polypoid lesions. Histological examination revealed only chronic
      inflammatory cell infiltration. In order to obtain a definite diagnosis, we
      performed endoscopic jumbo biopsy for the polypoid lesions after obtaining
      informed consent. Histological examination revealed marked lymphocyte
      infiltration, hemosiderin deposits and fibromuscular obliteration in the lamina
      propria, features similar to those of mucosal prolapsing syndrome. After anti
      diarrhetic treatment, clinical findings were improved. Thus, jumbo biopsy is
      useful for diagnosis and treatment of prolapsing mucosal polyps.

PMID- 16570363
TI  - Dermatomyositis associated with hepatocellular carcinoma in an elderly female
      patient with hepatitis C virus-related liver cirrhosis.
AB  - A 79-year-old female patient with hepatitis C virus-related liver cirrhosis was
      diagnosed as having hepatocellular carcinoma (HCC) with a diameter of 2.0 cm. She
      refused therapy for HCC. Nine months after the diagnosis, she developed
      dermatomyositis when the HCC enlarged to a diameter of 6.0 cm. She underwent
      therapy for dermatomyositis, and then transcatheter arterial chemoembolization
      for HCC. Although the manifestations of dermatomyositis improved and entire tumor
      necrosis was achieved, she died of pneumonia 2 mo after the treatment of HCC. HCC
      and/or chronic hepatitis C virus infection might be involved in the pathogenesis
      of dermatomyositis.

PMID- 16570365
TI  - Malignant phyllode tumor metastatic to the duodenum.
AB  - Phyllode tumor (PT) is extremely rare tumor of the breast. Distant metastasis
      occurs in 10%-20% of patients with malignant phyllode tumor. The most common
      sites of metastases are the lungs and bones. Although theoretically any organ may
      have metastasis, an isolated duodenum metastasis has not been documented as yet
      in the English-language literature. We report herein a case with a isolated
      duodenal metastasis from PT of breast in a 31 year-old-woman who underwent right
      mastectomy 4 years before because of the recurrent malignant PT. She presented to
      our hospital with massive upper gastrointestinal bleeding. Clinical evaluation
      revealed a huge mass originated from duodenum. Urgent laparotomy and
      pancreaticoduodenectomy were carried out in order to remove the bleeding duodenal
      mass. The pathologic examination of the resected specimen showed a malignant
      spindle cell tumor consistent with metastatic malignant PT. Our case of
      gastrointestinal bleeding due to an isolated duodenal metastasis as a result of
      hematogenous spread from malignant phyllode tumor of breast is unique in the
      English literature and pancreaticoduodenectomy is a curative treatment for
      patients with isolated duodenal involvement.

PMID- 16570366
TI  - Light chain-associated Fanconi syndrome with nephrotic-range proteinuria.

PMID- 16570364
TI  - Spontaneous regression of hepatic inflammatory pseudotumor with primary biliary
      cirrhosis: case report and literature review.
AB  - Hepatic inflammatory pseudotumor (IPT) is a rare benign non-neoplastic lesion
      characterized by proliferating fibrous tissue infiltrated by inflammatory cells.
      The exact etiology of IPT remains unclear. Although the association of IPT with
      systemic inflammatory disorders has been well established, a specific
      relationship with cholangitis is distinctly rare. We report a case of spontaneous
      regression of hepatic IPT with primary biliary cirrhosis (PBC). To date, only two
      cases of IPT with PBC have been reported. In our case, however, IPT developed
      during the course of improvement of cholangitis of PBC induced by effective
      treatment, differing from two previously reported cases. Our case indicates that
      the development of IPT does not also relate to the activity of cholangitis and/or
      hyper gamma-globulinemia, since our case was confirmed radiologically to be free
      of IPT when biliary enzymes and immunoglobulins were much higher than the
      corresponding values on admission. Comparison of our case with the two previously
      reported cases suggests that IPT occurring with PBC does not represent the same
      disease entity or be a bystander for PBC.

PMID- 16570368
TI  - [Scientific evaluation of the annual Turkish Psychiatry European international
      meetings continuously from 1996-2005].

PMID- 16570369
TI  - Radioactive contamination in urban areas. Proceedings of a conference. May 7-9,
      2003.Roskilde, Denmark.

PMID- 16570367
TI  - [Just the Turkish language, please].

PMID- 16570370
TI  - Pioneers in cardiology: Sir Magdi Yacoub.

PMID- 16570372
TI  - Thrombolysis in a rural community.

PMID- 16570371
TI  - A diagnostic dilemma of right lower lobe collapse caused by pulmonary
      bilharsiasis.
AB  - A 32-year-old male was presented with massive haemoptysis. An urgent chest X-ray
      (Fig. 1a) and CT chest (Fig. 1b-e) was done revealing a right lower lobe
      consolidation collapse. An urgent rigid bronchoscopy was performed to localize
      the source of bleeding and try to control it. A right lower lobectomy was done
      using a double-lumen endotracheal tube. Preoperative and intraoperative
      impressions of non-specific inflammation were accused to be the aetiology.
      Histopathology revealed pulmonary venous congestion with bilharsial ova.

PMID- 16570374
TI  - Abstracts of the 9th International Geneva/Springfield Symposium on Advances in
      Alzheimer Therapy. April 19-22, 2006, Geneva, Switzerland.

PMID- 16570375
TI  - Abstracts of the 79th Annual Meeting of the Japanese Pharmacological Society,
      March 8-10, 2006, Yokohama, Japan.

PMID- 16570373
TI  - Abstracts of the American Urological Association annual meeting, Atlanta,
      Georgia, USA, May 20-25, 2006.

PMID- 16570376
TI  - Abstracts of the 14th Association of European Psychiatrists Congress, Nice,
      France, 4-8 March 2006.

PMID- 16570377
TI  - An evaluation of the role of risk-based decision-making in a former manufactured
      gas plant site remediation.
AB  - Environmental remediation decisions are driven by the need to minimize human
      health and ecological risks posed by environmental releases. The Risk Assessment
      Guidance for Superfund Sites enunciates the principles of exposure and risk
      assessment that are to be used for reaching remediation decisions for sites under
      Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA).
      Experience with remediation management under CERCLA has led to recognition of
      some crucial infirmities in the processes for managing remediation: cleanup
      management policies are ad hoc in character, mandates and practices are strongly
      conservative, and contaminant risk management occurs in an artificially narrow
      context. The purpose of this case study is to show how a policy of risk-based
      decision-making was used to avoid customary pitfalls in site remediation. This
      case study describes the risk-based decision-making process in a remedial action
      program at a former manufactured gas plant site that successfully achieved timely
      and effective cleanup. The remediation process operated outside the confines of
      the CERCLA process under an administrative consent order between the utility and
      the New Jersey Department of Environmental Protection. A residential use end
      state was negotiated as part of this agreement. The attendant uncertainties,
      complications, and unexpected contingencies were overcome by using the likely
      exposures associated with the desired end state to structure all of the
      remediation management decisions and by collecting site-specific information from
      the very outset to obtain a detailed and realistic characterization of human
      health risks that needed to be mitigated. The lessons from this case study are
      generalizable to more complicated remediation cases, when supported by
      correspondingly sophisticated technical approaches.

PMID- 16570378
TI  - Pott's spine and paraplegia.
AB  - Spinal tuberculosis is usually secondary to lung or abdominal involvement and may
      also be the first manifestation of tuberculosis. Spinal tuberculosis (often
      called Pott's disease) is by definition, an advanced disease, requiring
      meticulous assessment and aggressive systemic therapy. Physicians should keep the
      diagnosis in mind, especially in a patient from a group with a high rate of
      tuberculosis infection. This review aims on updating the knowledge on spinal
      tuberculosis and its management. Skeletal involvement has been reported to occur
      in approximately 10% of all patents with extrapulmonary tuberculosis, and half of
      these patients develop infection within the spinal column. Symptoms of spinal
      tuberculosis are back pain, weakness, weight loss, fever, fatigue, and malaise.
      It is much more prone to develop neurological manifestation, paraplegia of
      varying degree. The palpation of spinous process in routine clinical examination
      is the most rewarding clinical method and is an invaluable measure for early
      recognition. Diagnosis of spinal tuberculosis is made on the basis of typical
      clinical presentation along with systemic constitutional manifestation and the
      evidence of past exposure to tuberculosis or concomitant visceral tuberculosis.
      Magnetic resonance imaging can define the extent of abscess formation and spinal
      cord compression. The diagnosis is confirmed through percutaneous or open biopsy
      of the spinal lesion. Surgery is necessary as an adjunct to antibiotic therapy if
      the vertebral infection produces an abscess, vertebral collapse, or neurologic
      compression. Some patents need aggressive supportive care owing to tuberculous
      meningitis or encephalopathy. Moreover, the importance of immediate commencement
      of appropriate treatment and its continuation for adequate duration along with
      the proper counseling of the patient and family members should not be
      underestimated for successful and desired outcome.

PMID- 16570379
TI  - Audiovestibular functioning in patients with panic disorder.
AB  - OBJECTIVE: The objective of this study was to investigate audiovestibular
      function in patients with panic disorder and healthy subjects by using vestibular
      and audiologic tests. METHODS: Thirty-four panic disorder patients and 20 healthy
      control subjects were assessed by using clinical otoneurological examination,
      pure tone audiometry, tympanometry, and electronystagmography (ENG). All patients
      were evaluated with the Panic and Agoraphobia Scale (PAS), the Hamilton Anxiety
      Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the State
      Trait Anxiety Inventory (STAI). RESULTS: On vestibular testing, abnormal
      responses were more prevalent in panic disorder patients compared to healthy
      controls. The presence of agoraphobia in panic disorder patients did not make a
      significant difference on vestibular test results. The only variable that may be
      a predictor of vestibular abnormalities in panic disorder patients was found to
      be dizziness between attacks. CONCLUSION: The results show that dizziness between
      panic attacks may warrant audiovestibular testing among other medical
      investigations.

PMID- 16570381
TI  - Mosquito vector control and biology in Latin America--a 15th symposium.
      Abstracts.
AB  - The 15th Annual Latin American symposium presented by the American Mosquito
      Control Association (AMCA) was held as part of the 71st Annual Meeting in
      Vancouver, British Columbia, Canada, in April 2005. The principal objective, as
      for the previous 14 symposia, was to promote participation in the AMCA by vector
      control specialists, public health workers, and academicians from Latin America.
      This publication includes summaries of 40 presentations that were given orally in
      Spanish or presented as posters by participants from 8 countries in Latin America
      and the USA. Topics addressed in the symposium included results from chemical and
      biological control programs and studies; studies of insecticide resistance; and
      population genetics, molecular, ecological, and behavioral studies of vectors of
      dengue (Aedes aegypti and Ae. albopictus) and other arboviruses, malaria
      (Anopheles albimanus, An. aquasalis, An. neomaculipalpus, An.
      pseudopunctipennis), leishmaniasis (Lutzomyia), and Chagas Disease (Triatoma), as
      well as a vaccine for control of Boophilus ticks on cattle.

PMID- 16570380
TI  - [Legionnaire's disease outbreak].
AB  - BACKGROUND AND OBJECTIVE: To describe an outbreak of Legionella pneumophila
      serogroup 1 in Mataro, Catalunya, Spain, in August 2002. The source of the
      microorganism was a cooling tower. PATIENTS AND METHOD: Prospective and
      observational study with analysis of epidemiological, clinical, and
      microbiological data. RESULTS: 151 patients were affected (62% male), with a mean
      age of 58.4 years old. Seven patients were classified as Pontiac Fever and 144
      suffered from pneumonia. The diagnosis of pneumonia was confirmed in 79% of
      cases, was considered suspicious in 14% and probable in 7%. Forty per cent of
      patients were smokers and 53.5% had comorbidities, mainly diabetes mellitus
      (22%). Chief symptoms were fever (97%), chills and muscular pain (63%
      respectively), headache (54%) and cough (53%). Pulmonary condensation was the
      more frequent radiological feature (71%). Normal pulmonary exploration was
      observed in 38%. Forty-three per cent of cases were severely ill, and 16% of
      patients belonged to Fine's IV and V class. Antigenuria was the most important
      test for diagnosis, which confirmed 76% of cases. Legionella spp. was obtained in
      respiratory secretions of 10 patients. Molecular analysis confirmed clonality
      between respiratory microorganisms and that obtained in the cooling tower.
      CONCLUSION: The outbreak involved an important number of subjects in a short
      period of time. Antigenuria was the most useful test. However, the isolation of
      L. pneumophila from patients permitted the prompt identification of
      microorganism's source in a cooling tower. The low mortality observed probably
      relates to a rapid diagnosis and its target treatment.

PMID- 16570382
TI  - Two-color nanoparticles identify single molecules.

PMID- 16570383
TI  - SFC separation of peptides.

PMID- 16570384
TI  - Proteomics reveals proteins in paint.

PMID- 16570385
TI  - Cytoskeletal proteins get their own rooms.

PMID- 16570386
TI  - Nanotubes probe cellular secrets.

PMID- 16570387
TI  - Extraordinary IR transmission with metallic arrays of subwavelength holes.

PMID- 16570388
TI  - In vivo measurements of neurotransmitters by microdialysis sampling.
AB  - The brain contains a vast network of neurons that connect with each other at
      specialized junctions called synapses.A synapse consists of a presynaptic
      terminal (the "sending"neuron) and a postsynaptic bouton (the "receiving"
      neuron)that are separated by a gap of 5-50 nm (Figure 1). Chemicals released into
      this synaptic gap interact with receptors on the postsynaptic neuron. This leads
      to intracellular changes in the postsynaptic neuron-for example, an altered
      membrane potential or gene expression. The chemical signal is terminated by
      transporter proteins that transfer transmitter molecules across the membrane to
      the intracellular space (a process known as "reuptake")or enzymes that degrade
      the transmitter in the vicinity of the synapse (Figure 1). This classical view of
      neurotransmission might be considered point-to-point or"wired" communication
      because neurons communicate only with neurons to which they are specifically
      connected. In addition,neurotransmitters can activate receptors at more distant
      sites either by escaping the synapse or by being directly released into
      extrasynaptic space. This longer-range communication has been called "volume"
      transmission (1, S1; S references can be found in Supporting Information). All
      brain functions, from controlling movement to emotions, involve these two forms
      of chemical communication. Analytical chemistry has an important role to play in
      developing our understanding of the brain by providing tools for identification
      and measurement of the many chemicals involved in neurotransmission.

PMID- 16570389
TI  - Cell tracking in vivo with MRI.

PMID- 16570390
TI  - Diving into droplets.

PMID- 16570391
TI  - Canadian Healthcare Excellence in Quality Award (CHEQA).

PMID- 16570393
TI  - [Ambulatory chemotherapy in the Fukuoka University hospital].

PMID- 16570394
TI  - Periodontal manifestations during menstruation (as if PMS weren't enough, now add
      swollen gums!).

PMID- 16570392
TI  - [Application of navigation system for otorhinolaryngological surgical procedures-
      special reference to nasal and paranasal diseases].

PMID- 16570395
TI  - [Ambulatory chemotherapy in the Saiseikai Kumamoto hospital].

PMID- 16570396
TI  - Pregnancy-associated death: a qualitative systematic review of homicide and
      suicide.
AB  - A systematic review of the literature on maternal homicide and suicide was
      performed to understand the causes of pregnancy-associated death. Forty-four
      studies examined homicide and/or suicide and pregnancy-associated death (defined
      as the death of a woman, from any cause, while she is pregnant or within 1 year
      of termination of pregnancy) (1). Of these studies, 747 homicides and 349
      suicides were identified. All studies were included except duplicate datasets,
      case reports of less than 3 events, suicide attempts, unpublished manuscripts,
      review articles, or non-English studies. Homicide is a leading cause of pregnancy
      associated death and suicide is also an important cause of death among pregnant
      and recently pregnant women. Healthcare providers should understand that homicide
      is a leading cause of pregnancy-associated death, most commonly as a result of
      partner violence. Therefore, screening for both partner violence and suicidal
      ideation are essential components of comprehensive medical care for women during
      and after pregnancy.

PMID- 16570398
TI  - Female sexual dysfunction: principles of diagnosis and therapy.
AB  - Female sexual dysfunction is a common health problem, affecting approximately 43%
      of women. Female sexual dysfunction is defined as disorders of libido, arousal,
      orgasm, and sexual pain that lead to personal distress or interpersonal
      difficulties. It is frequently multifactorial in etiology, with physiological and
      psychologic roots. Approaching female sexual dysfunction involves an open
      discussion with the patient, followed by a thorough physical examination and
      laboratory testing. Therapy consists of patient and partner education, behavior
      modification, and may include individualized pharmacotherapy. Ultimately, as
      awareness and research in the field grows, it is hoped that a better
      understanding of the physiology and pharmacology of the female sexual response
      will be achieved.

PMID- 16570397
TI  - Spontaneous adrenal hemorrhage during pregnancy: a review of the literature and a
      case report of successful conservative management.
AB  - Spontaneous adrenal hemorrhage is an acute hemorrhage of the adrenal gland that
      occurs in the absence of trauma or anticoagulant therapy. The incidence of this
      condition in pregnancy is unknown. We describe a patient with spontaneous
      unilateral adrenal hemorrhage that occurred during the third trimester of
      pregnancy. She was successfully managed conservatively with complete resolution
      of symptoms and had an uncomplicated perinatal outcome. We review the literature
      on spontaneous adrenal hemorrhage, including clinical signs and symptoms,
      diagnostic tests, and management of spontaneous adrenal hemorrhage, to help other
      practitioners to recognize and appropriately treat this rare condition.

PMID- 16570399
TI  - Effect of wavefront error on 10(-7) contrast measurements.
AB  - Received October 11, 2005; accepted November 10, 2005; posted December 2, 2005
      (Doc. ID 65234) We have measured a contrast of 6.5 x 10(-8) from 10 to 25
      lambda/D in visible light on the Extreme Adaptive Optics testbed, using a shaped
      pupil for diffraction suppression. The testbed was designed with a minimal number
      of high-quality optics to ensure low wavefront error and uses a phase-shifting
      diffraction interferometer for metrology. This level of contrast is within the
      regime needed for imaging young Jupiter-like planets, a primary application of
      high-contrast imaging. We have concluded that wavefront error, not pupil quality,
      is the limiting error source for improved contrast in our system.

PMID- 16570400
TI  - Average intensity and spreading of an elliptical gaussian beam propagating in a
      turbulent atmosphere.
AB  - An analytical formula for the average intensity of an elliptical Gaussian beam
      (EGB) propagating in a turbulent atmosphere is derived. The spreading properties
      of an EGB in a turbulent atmosphere are studied. It is found that an EGB will
      eventually become a circular Gaussian beam in a turbulent atmosphere. This
      interesting phenomenon is quite different from the propagation of an EGB in free
      space. The evolution properties are closely related to the parameters of the beam
      and the turbulent atmosphere.

PMID- 16570401
TI  - Synchronization of optical polarization conversion and scattering in chiral
      fibers.
AB  - We demonstrate that polarization transformation and scattering in adiabatically
      twisted single-mode birefringent optical fibers is synchronized so that light in
      one evolving elliptically polarized mode is freely transmitted while orthogonally
      polarized light is scattered out of the fiber. Thus, linearly polarized radiation
      initially oriented along the fast axis of the untwisted fiber is transformed to
      circularly polarized light with the same sense of rotation as the twisted fiber
      and is scattered out of the fiber. When the fiber twist is first accelerated and
      then decelerated, the fiber becomes a broadband, low-insertion-loss, linear
      polarizer.

PMID- 16570402
TI  - Microjoule-level all-polarization-maintaining femtosecond fiber source.
AB  - We report on a high-power, high-energy femtosecond fiber source based on direct
      amplification of parabolic pulses from an environmentally stable passively mode
      locked fiber oscillator in an Yb-doped single-polarization photonic crystal
      fiber. The special pulse shape allows for the generation of high-quality
      femtosecond pulses beyond nonlinearity limits. The system delivers a pulse energy
      of 1.2 microJ (21 W average power) at a repetition rate of 17 MHz and a pulse
      duration of 240 fs in a linearly polarized beam with diffraction-limited quality.

PMID- 16570403
TI  - Multichannel vector sum phase shifter.
AB  - A novel multichannel vector sum phase shifter that is suitable for phased array
      antenna applications is demonstrated. Each channel is implemented using a
      distinct optical wavelength. Selective control of each channel is performed using
      an acousto-optic polarization coupler. The concept is successfully demonstrated
      for two individually controlled channels. For each channel, a continuously
      variable frequency linear phase shift is demonstrated between DC and 7 GHz, with
      the phasing range exceeding 100 degrees.

PMID- 16570404
TI  - Third-order dispersion and bound states of pulses in a fiber laser.
AB  - The effect of third-order dispersion on bound states of pulses in the anomalous
      dispersion fiber ring laser is analyzed experimentally and numerically. The bound
      states are formed by an interaction through dispersive waves. Due to third-order
      dispersion, the resonant sideband spectrum is asymmetric. The most intense
      sideband drives the interaction in these bound states and fixes their separation
      to a discrete set of values.

PMID- 16570405
TI  - Frequency mixing of photorefractive and ferroelectric gratings in lithium niobate
      crystals.
AB  - Holographically recorded photorefractive gratings in periodically poled lithium
      niobate crystals (PPLNs) are investigated. The principal spatial frequency K of
      the grating is strongly suppressed. Sideband gratings with grating vectors K +/-
      G appear. From the measurements the domain grating vector G and the duty cycle of
      the domain structure can be obtained. These findings allow for fast
      nondestructive quality inspection of PPLN and are of importance for any optical
      application combining holography and PPLN.

PMID- 16570406
TI  - Superresolved imaging of remote moving targets.
AB  - We present a superresolving approach that allows one to exceed the diffraction
      limit and recover highly resolved contours of moving targets from a sequence of
      low-resolution images. The presented approach is suitable for remote sensing
      applications. The resolution decoding algorithm that is used to recover the high
      resolution features of the target can be run partially via optical means and that
      way can be used to reduce the required computational complexity.

PMID- 16570407
TI  - Chromatically dispersed interferometry with wavelet analysis.
AB  - A new white-light interferometry point sensor utilizing a chromatically dispersed
      depth detection field is addressed. Monitoring the interference in the optical
      frequency domain allows for microscopic height detection without the necessity of
      a mechanical axial scan. The problem of limited dynamic range in previously
      reported spectral interferometric schemes is solved by forming a high-contrast
      interference window due to the chromatically dispersed focusing of the detection
      field. In a proof-of-principle experiment, the position of a reflecting object
      could be retrieved with a focus of 0.8 NA over an axial range of 30 microm by
      analyzing the phase of the emerging interference wavelets.

PMID- 16570408
TI  - All-fiber passively mode-locked laser oscillator at 1.5 microm with watts-level
      average output power and high repetition rate.
AB  - We report on a passively mode-locked all-fiber laser oscillator at 1.5 microm
      based on heavily doped phosphate-glass active fiber. An active fiber only 20 cm
      long is sufficient to produce as much as 2.4 W of average output power directly
      from the oscillator. The width of the mode-locked pulses varies from 8 ps at the
      lowest output power in the mode-locked state to 44 ps at the highest power. Our
      picosecond laser oscillator features a high repetition rate of 95 MHz and high
      peak pulse power of approximately 540 W. The oscillator combines the convenience
      of all-fiber construction with power performance that was previously achievable
      only with mode-locked bulk-optic laser oscillators or more complex systems
      involving fiber amplifiers.

PMID- 16570409
TI  - Effect of multiple wavelengths on laser-induced damage in KH(2-x)DxPO4 crystals.
AB  - Laser-induced damage is a key factor that constrains the ways in which optical
      materials are used in high-power laser systems. We study the size and density of
      bulk laser-induced damage sites formed during frequency tripling in a DKDP
      crystal. The characteristics of the damage sites formed during tripling, for
      which 1053, 526, and 351 nm light is simultaneously present, are compared to
      those of damage sites formed by 351 nm light alone. The fluence of each
      wavelength is calculated as a function of depth with a full 4D(x,y,z,t) frequency
      conversion code and compared with measured damage density and size distributions.
      The density of damage is found to be governed predominantly by 351 nm light with
      some lesser, though nonnegligible, contribution from 526 nm light. The 1053 nm
      light does not appear to contribute to the damage density. The morphology of the
      damage sites, however, is seen to be relatively insensitive to wavelength and to
      depend only on total fluence of all wavelengths present. The strong and
      negligible wavelength dependences of initiation density and damage morphology,
      respectively, indicate that the dominant energy deposition mechanism varies
      during the damaging pulse.

PMID- 16570410
TI  - Frequency locking to the center of a 532 nm iodine absorption line by using
      stimulated brillouin scattering from a single-mode fiber.
AB  - A simple method for frequency locking a frequency-doubled Nd:YAG laser to the
      center of line 1109 of the iodine absorption spectrum is described. The 31.6 GHz
      frequency shift provided by stimulated-Brillouin scattering from a single-mode
      silica fiber provides a probe signal that lies on the edge of line 1105 of the
      iodine spectrum. We adjust the frequency of the laser to maintain the
      transmission of a 5 cm iodine absorption cell at a value that places the
      unshifted laser line in the center of line 1109.

PMID- 16570411
TI  - Very low-refractive-index optical thin films consisting of an array of SiO2
      nanorods.
AB  - The refractive-index contrast in dielectric multilayer structures, optical
      resonators, and photonic crystals is an important figure of merit that creates a
      strong demand for high-quality thin films with a low refractive index. A SiO2
      nanorod layer with low refractive index of n = 1.08, to our knowledge the lowest
      ever reported in thin-film materials, is grown by oblique-angle electron-beam
      deposition of SiO2. A single-pair distributed Bragg reflector employing a SiO2
      nanorod layer is demonstrated to have enhanced reflectivity, showing the great
      potential of low-refractive-index films for applications in photonic structures
      and devices.

PMID- 16570412
TI  - Amplitude modulation and apodization of quasiphase-matched interactions.
AB  - We propose several techniques to modulate the local amplitude of quasi-phase
      matched (QPM) interactions in periodically poled lithium niobate waveguides and
      demonstrate apodization by using each of these techniques. When the hard edges
      are removed in the spatial profile of the nonlinear coupling, the sidelobes of
      the frequency tuning curves are suppressed by 13 dB or more, compared with a
      uniform grating, consistent with theoretical predictions. The sidelobe-suppressed
      gratings are useful for frequency conversion devices in optical communication
      systems to minimize interchannel cross talk, while the amplitude modulation
      techniques in general have potential uses in applications that require altering
      the tuning curve shapes.

PMID- 16570413
TI  - Dynamics of vector solitons and vortices in two-dimensional photonic lattices.
AB  - We study discrete vector solitons and vortices in two-dimensional photonic
      lattices with Kerr nonlinearity and demonstrate novel types of stable,
      incoherently coupled dipoles and vortex-soliton complexes that can be excited by
      Gaussian beams. We also discuss what we believe to be novel scenarios of the
      charge-flipping instability of incoherently coupled discrete vortices.

PMID- 16570414
TI  - Dependence of silicon position-detector bandwidth on wavelength, power, and bias.
AB  - We have developed a two-LED wobbler system to generate the spatial displacement
      of total light intensity on a detector surface, facilitating the acquisition of
      frequency responses up to 600 kHz with high accuracy. We have used this setup to
      characterize the low-pass filtering behavior of silicon-based position detectors
      for wavelengths above 850 nm by acquiring the frequency responses of several
      quadrant detectors and position-sensitive detectors as functions of wavelength,
      applied bias voltage, and total light power. We observed an increase in bandwidth
      for an increase in applied bias voltage and incident-light intensity. The
      combined effect of these parameters is strongly dependent on the detector used
      and has significant implications for the use of these detectors in scanning probe
      and optical tweezers applications.

PMID- 16570415
TI  - Longitudinal anisotropy of the photoinduced molecular migration in azobenzene
      polymer films.
AB  - The effects of tightly focused, higher-order laser beams on the photoinduced
      molecular migration and surface deformations in azobenzene polymer films are
      investigated. We demonstrate that the surface relief is principally triggered by
      longitudinal fields, i.e., electric fields polarized along the optical axis of
      the focused beam. Our findings can be explained by the translational diffusion of
      isomerized chromophores when the constraining effect of the polymer-air interface
      is considered.

PMID- 16570416
TI  - High birefringence of the yttrium vanadate crystal in the middle wavelength
      infrared.
AB  - A high birefringence of over 0.21 for the yttrium vanadate (YVO4) crystal in the
      middle wavelength infrared (i.e., 3-5 microm) was measured. A Fourier transform
      infrared spectrometer was employed in the channel spectra technique to obtain the
      measurements.

PMID- 16570417
TI  - Self-interaction and mutual interaction of complex-argument Laguerre-Gauss beams.
AB  - A general method is presented for the determination of the time-averaged power
      associated with the self-interaction and the mutual interaction of cylindrically
      symmetric complex-argument Laguerre-Gauss beams. The method is also applied for
      the determination of two useful moments of the time-averaged Poynting vector.

PMID- 16570418
TI  - Cancellation of light shifts in an N-resonance clock.
AB  - We demonstrate that first-order light shifts can be canceled for an all-optical,
      three-photon-absorption resonance (N-resonance) on the D1 transition of 87Rb.
      This light-shift cancellation facilitates improved frequency stability for an N
      resonance clock. For example, by using a tabletop apparatus designed for N
      resonance spectroscopy, we measured a short-term fractional frequency stability
      (Allan deviation) of approximately/= 1.5 x 10(-11) tao1/2 for observation times
      of 1 s < or = tao < or = 50 s. Further improvements in frequency stability should
      be possible with an apparatus designed as a dedicated N-resonance clock.

PMID- 16570420
TI  - Timing noise measurement of 320 GHz optical pulses using an improved
      optoelectronic harmonic mixer.
AB  - An improved optoelectronic harmonic mixer (OEHM) has been employed for measuring
      the timing noise of 320 GHz optical pulses that are generated from a 160 GHz mode
      locked laser diode by the temporal Talbot effect. The OEHM makes use of a low
      drive voltage LiNbO3 modulator and a W-band unitraveling carrier photodiode for
      converting the 320 GHz pulse intensity into a low-frequency electrical signal.
      The time domain demodulation technique has been used for the precise evaluation
      of phase noise power spectral density. The rms timing jitter has been estimated
      to be 311 fs for the 10 Hz-18.6 MHz bandwidth.

PMID- 16570419
TI  - Imaging and sizing of diamond nanoparticles.
AB  - Typical disturbances of biological environment such as background scatter and
      refractive index variations have little effect on the size-dependent scattering
      property of highly refractive nanocrystals, which are potentially attractive
      optical labels. We report on what is to our knowledge the first investigation of
      these scattering optical labels, and their sizing, in particular, by imaging at
      subvideo frame rates and analyzing samples of diamond nanocrystals deposited on a
      glass substrate in air and in a matrix of weakly scattering polymer. The
      brightness of a diffraction-limited spot appears to serve as a reliable measure
      of the particle size in the Rayleigh scattering limit.

PMID- 16570421
TI  - Full control of the spectral polarization of ultrashort pulses.
AB  - The spectral polarization of an ultrashort pulse is fully controlled by a novel
      pulse shaper design, including three liquid-crystal spatial light modulator
      arrays at three different orientations. The added degree of controllability
      permits generation of previously unattainable pulse shapes, with possible
      applications in multidimensional spectroscopy, coherent control, and ultrafast
      polarization gating.

PMID- 16570423
TI  - Cavity-enhanced optical parametric chirped-pulse amplification.
AB  - A novel method for the generation of high-energy ultrashort optical pulses is
      described and studied theoretically and numerically. Through the combination of
      parametric amplification and enhancement cavities, this method opens a route to
      generate few-cycle pulses at unprecedented average power levels through the use
      of a low-energy, high average-power pump source and energy storage in the
      enhancement cavity. Dispersion in the enhancement cavity ceases to be a concern
      with the use of long pump pulses. Limitations set by the Kerr nonlinearity of the
      amplifier crystal are analyzed, and ways to overcome them using self-defocusing
      nonlinearities are discussed.

PMID- 16570422
TI  - Transmission properties of terahertz pulses through subwavelength double split
      ring resonators.
AB  - We present a terahertz time-domain spectroscopy study of the transmission
      properties of planar composite media made from subwavelength double split-ring
      resonators (SRRs). The measured amplitude transmission spectra reveal a resonance
      near 0.5 THz, the central frequency of most ultrafast terahertz systems, for one
      SRR orientation in normal-incidence geometry. This resonance is attributed to the
      effect of electric excitation of magnetic resonance of the SRR arrays. In
      addition, the influences of background substrate, lattice constant, and the
      shapes of the SRRs on the terahertz resonance are experimentally investigated and
      agree well with the results of recent numerical studies.

PMID- 16570424
TI  - Direct space-to-time pulse shaper with reflective arrayed waveguide gratings and
      phase masks.
AB  - We demonstrate for what we believe to be the first time the generation of
      sequences of ultrafast optical pulses by phase modulation in a direct space-to
      time pulse shaper. The pulse shaper is based on the combination of a reflective
      arrayed waveguide grating multiplexer and an external reflector. The spatial
      modulation of the phase was obtained by fabricating corrugated patterns on the
      external reflector. We demonstrate that pulse sequences with different repetition
      rates can be obtained by changing the period in the patterned mask.

PMID- 16570425
TI  - Energy extraction improvement in picosecond amplifiers by pulse tilting.
AB  - We report a novel tilted pulse amplification technique that, in contrast with the
      chirped-pulse amplification method, allows stretching of ultrashort pulses
      independently upon the initial pulse bandwidth. A gain factor of 4.5 and good
      reconstruction of a 15 ps pulse after stretching to 200 ps in a double-pass end
      pumped Nd:YAG amplifier have been achieved.

PMID- 16570426
TI  - Acquiring 1053 nm femtosecond laser emission by optical parametric amplification
      based on supercontinuum white-light injection.
AB  - We report a terawatt-Ti:sapphire-laser-pumped high-energy femtosecond optical
      parametric amplifier (OPA) with supercontinuum white-light injection. Signal
      pulses with a duration less than 100 fs and energy up to 4 mJ are obtained with
      large-aperture LiNbO3 crystals. This megajoule-class femtosecond OPA at 1053 nm
      presents a feasible alternative to optical parametric chirped-pulse amplification
      and is ready to be applied to petawatt lasers.

PMID- 16570427
TI  - Generation of helical Ince-Gaussian beams with a liquid-crystal display.
AB  - We generate helical Ince-Gaussian (HIG) beams by using complex amplitude and
      phase masks encoded onto a liquid-crystal display (LCD). These beams display an
      intensity pattern consisting of elliptic rings, whose number and ellipticity can
      be controlled, and a phase exhibiting a number of in-line vortices, each with a
      unitary topological charge. We show experimental results that display the
      properties of these elliptic dark hollow beams. We introduce a novel interference
      technique for generating the object and reference beams by using a single LCD and
      show the vortex interference patterns. We expect that these HIG beams will be
      useful in optical trapping applications.

PMID- 16570428
TI  - Switchable gratings by spatially periodic alignment of liquid crystals via
      patterned photopolymerization.
AB  - Spatially periodic patterning of the anchoring condition of a nematic liquid
      crystal (NLC) within a polymer matrix via a patterned photopolymerization affords
      a novel and facile method to prepare electrically switchable diffraction
      gratings. UV irradiation through a photomask of two comonomers, with opposite
      tendencies to align the NLC and also with different reactivity ratios, leads to
      definition of areas with either homeotropic or planar alignment of the NLC.
      Photopolymerization-induced diffusion of the monomers accounts for the spatial
      distribution of the concentration of these monomers. The resulting diffraction
      gratings are switchable under low electric fields and possess structural
      stability offered by the polymer matrix.

PMID- 16570429
TI  - High-transmission hybrid-effect-assisted nanoaperture.
AB  - We present a C-aperture encircled by a groove that makes possible the hybrid
      effect of coupling surface plasmon resonance to propagating waves. Compared to a
      single C aperture, the groove-encircled aperture can increase transmission by a
      factor of 2.45 in the near field and by a factor of 1.88 in the far field,
      showing good agreement with our theoretical calculation.

PMID- 16570430
TI  - Three-port beam splitters-combiners for interferometer applications.
AB  - We derive generic phase and amplitude coupling relations for beam splitters
      combiners that couple a single port with three output ports or input ports,
      respectively. We apply the coupling relations to a reflection grating that serves
      as a coupler to a single-ended Fabry-Perot ring cavity. In the impedance-matched
      case such an interferometer can act as an all-reflective ring mode cleaner. It is
      further shown that in the highly undercoupled case almost complete separation of
      carrier power and phase signal from a cavity strain can be achieved.

PMID- 16570431
TI  - [Study on clinical effectiveness of acupuncture and moxibustion on acute Bell's
      facial paralysis: randomized controlled clinical observation].
AB  - OBJECTIVE: To investigate the adverse effects of acupuncture on the prognosis,
      and effectiveness of acupuncture combined with far infrared ray in the patient of
      acute Bell's facial paralysis within 48 h. METHODS: Clinically randomized
      controlled trial was used, and the patients were divided into 3 groups: group A
      (early acupuncture group), group B (acupuncture combined with far infrared ray)
      and group C (acupuncture after 7 days). The facial nerve functional
      classification at the attack, 7 days after the attack and after treatment, the
      clinically cured rate of following-up of 6 months, and the average cured time,
      the cured time of complete facial paralysis were observed in the 3 groups.
      RESULTS: There were no significant differences among the 3 groups in the facial
      nerve functional classification 7 days after the attack, the clinically cured
      rate of following-up of 6 months and the average cured time (P > 0.05), but the
      cured time of complete facial paralysis in the group A and the group B were
      shorter than that in the group C (P < 0.05). CONCLUSION: The patient of acute
      Bell's facial paralysis can be treated with acupuncture and moxibustion, and
      traditional moxibustion can be replaced by far infrared way.

PMID- 16570432
TI  - [Effects of moxibustion at Zusanli (ST 36) and Xuanzhong (GB 39) on
      cerebrovascular function in the patient of ischemic apoplexy].
AB  - OBJECTIVE: To explore the mechanism of moxibustion at Zusanli (ST 36) and
      Xuanzhong (GB 39) treatment of ischemic apoplexy, and to evaluate the clinical
      therapeutic effect. METHODS: With the design of sequential trial, the patients
      were divided into a treatment group and a control group. The treatment group were
      treated by addition with moxibustion at Zusanli (ST 36) and Xuanzhong (GB 39) on
      the basis of basic expectant treatment, once each day, for 20 consecutive days;
      and the control group with basic expectant treatment for 20 days. Changes of
      cerebrovascular functions before and after treatment were investigated by
      transcranial Doppler ultrasound (TCD) in the matched-pair's patients of ischemic
      apoplexy; the clinical therapeutic effect was assessed by nervous function defect
      before and after treatment. RESULTS: All the test lines of the research targets
      reached to the effective margin the sequential trial figure, with a significant
      difference as compared with the control group (P < 0.05). CONCLUSION: Moxibustion
      at Zusanli (ST 36) and Xuanzhong (GB 39) has good regulative action on cerebral
      vasomotorial response, auto-regulation of cerebral blood flow, and establishment
      of collateral circulation, and improves recovery nervous functions.

PMID- 16570433
TI  - [Controlled observation on Guan-moxibustion and suspended moxibustion for
      treatment of herpes simplex virus facial neuritis].
AB  - OBJECTIVE: To evaluate clinical therapeutic effect of Guan-moxibustion on herpes
      simplex virus facial neuritis. METHODS: One hundred and sixty cases were enrolled
      in 3 centers and 157 cases were completed the study. All he patients were
      randomly divided into 2 groups, a Guan-moxibustion group and a suspended
      moxibustion plus acupuncture group. All of them were treated with basic
      acupuncture, and the Guan-moxibustion group were added with Guan-moxibustion and
      the suspended moxibustion group with suspended moxibustion. They were treated for
      8 weeks, and facial disability index (FDI) and House-Brackmann facial nerve
      grading system were used to assess therapeutic effects. RESULTS: The effective
      rate was 91.0% in the Guan-moxibustion group and 72.2% in the suspended
      moxibustion group with a significant difference between the two groups (P <
      0.05), the Guan-moxibustion being better than the suspended moxibustion group.
      CONCLUSION: The therapeutic effect of Guan-moxibustion plus acupuncture on herpes
      simplex virus facial neuritis is better than that of suspended moxibustion plus
      acupuncture.

PMID- 16570434
TI  - [Observation on therapeutic effect of aponeurotic system penetration needling on
      peripheral facial paralysis].
AB  - OBJECTIVE: To observe therapeutic effect of aponeurotic system penetration
      needling on peripheral facial paralysis. METHODS: One hundred and ten cases of
      peripheral facial paralysis were randomly divided into a Jingjin group (n=68) and
      a control group (n=42). The therapeutic effects of acute stage, resting stage and
      sequela stage, and the relation between the facial nerve lesion degree and the
      therapeutic effect were investigated. RESULTS: The effective rates of the two
      needling methods were respectively 98.5% and 90.5%, the Jing1in group being
      better than the control group (P < 0.05); at the acute stage, the therapeutic
      effect of acupuncture was obvious, and the therapeutic effect at the sequela
      stage and for the patient of nerve faulty type in the Jingjin group were better
      than that of the control group (P < 0.05). CONCLUSION: Acupuncture and
      moxibustion has definite therapeutic effect on facial paralysis at the acute
      stage and in the patient of nerve active type, and aponeurotic system penetration
      needling can be used for the patient of facial paralysis at the sequela stage or
      with nerve faulty type.

PMID- 16570436
TI  - [Therapeutic effect of point-through-point acupuncture on migraine and its
      effects on brain blood flow velocity].
AB  - OBJECTIVE: To study the clinical therapeutic effect of point-through-point
      acupuncture on migraine and its mechanisms. METHODS: Ninety cases of migraine
      were randomly divided into a treatment group and a control group, 45 cases in
      each group. The treatment group were treated with point-through-point acupuncture
      and the control group with normal needling method. Brain blood flow velocity was
      determined by TCD before and after treatment. RESULTS: The effective rate was
      97.8% in the treatment group, which was better than 80.0% in the control group (P
      < 0.05). And the point-through-point acupuncture could significantly improve the
      highest mean blood flow velocity of main arteries, with a significant difference
      between the two groups after treatment (P < 0.05). CONCLUSION: Point-through
      point acupuncture can be used for treatment of migraine, with a high cured rate
      and obvious therapeutic effect.

PMID- 16570435
TI  - [Clinical therapeutic effects of body acupuncture and ear acupuncture on juvenile
      simple obesity and effects on metabolism of blood lipids].
AB  - OBJECTIVE: To probe the optimal acupuncture treatment program for juvenile simple
      obesity. METHODS: Ninety cases were randomly divided into 3 groups: ear
      acupuncture group, body acupuncture group and control group. The patients of the
      control group were treated by regulating diet structure, increasing motion and
      mental direct of slimming, in the body acupuncture group, body acupuncture at
      Sanyinjiao (SP 6), Tianshu (ST 25), Zusanli (ST 36), etc. were added, and in the
      ear acupuncture group, acupuncture at ear acupoints Jidian (hunger point),
      Pizhixia (subcortex), earshenmen, etc. were added. Seventy days later, the
      therapeutic effects and changes of blood lipids were observed. And they were
      followed up after one month. RESULTS: The total effective rate was 69.23% in the
      body acupuncture group, 65.52% in the ear acupuncture group and 26.67% in the
      control group, with significant differences as the two acupuncture groups
      compared with the control group. And there were significant differences in total
      cholesterol (TC) and lower density lipid protein-cholesterol (LDL-C) as the two
      acupuncture groups compared with the control group. There was no significant
      difference between the two acupuncture groups in all the indexes. CONCLUSION:
      Both ear acupuncture and body acupuncture have obvious therapeutic effect on
      juvenile simple obesity, and have some actions on blood lipids.

PMID- 16570437
TI  - [Observation on therapeutic effect of acupuncture on late sudden deafness].
AB  - OBJECTIVE: To observe therapeutic effect of acupuncture on late sudden deafness
      of different types. METHODS: According to the principles of TCM syndrome
      differentiation treatment, 63 cases were treated with acupuncture, once very
      other day, 7 days constituting one course with a interval of 3 days between two
      courses. Changes of the hearing threshold, and the difference of therapeutic
      effects between different states of illness and different types were
      investigated. RESULTS: Four cases (6.3%) were cured, 17 cases (27.0%) were
      markedly effective, 19 cases (30.2%) were effective, and 23 cases (36.5%) were
      ineffective, the total effective rate being 63.5%; there was a significant
      difference in the mean hearing threshold before and after treatment (P < 0.05).
      CONCLUSION: The milder the state of illness, the better the therapeutic effect of
      the acupuncture; in addition, acupuncture has the best therapeutic effect for the
      type with decrease of the curve of audition, and better therapeutic effects for
      the types of upward invasion of phlegm-heat, and the type of stagnation of turbid
      phlegm in the middle-jiao.

PMID- 16570438
TI  - [Observation on therapeutic effect of rolling needle therapy on insomnia].
AB  - OBJECTIVE: To assess the effect-increasing action of rolling needle therapy on
      insomnia. METHODS: Sixty-four cases were randomly divided into a rolling needle
      treatment group and a control group, 32 cases in each group. The control group
      were treated with oral administration of clonazepam 4 mg, once each night, for 4
      consecutive weeks. The rolling needle therapy group were treated with the same
      treatment as the control group, plus the rolling needle stimulation of the back.
      The therapeutic effect was assessed by effective rate of sleep improvement and
      Pittsburgh sleep quality index (PSQI). RESULTS: After treatment there was a
      significant difference between the two groups in the score of PSQI (P < 0.01).
      CONCLUSION: The rolling needle therapy can increase the improving action of
      clonazepam on insomnia, and increase life quality of the patient.

PMID- 16570439
TI  - [Effects of the degrees of anxiety and depression on the therapeutic effect of
      acupuncture in the patient of insomnia].
AB  - OBJECTIVE: To probe factors of influencing therapeutic effects of acupuncture in
      the patient of insomnia. METHODS: According to scores of degrees of anxiety and
      depression, 52 cases of insomnia were divided into 3 groups, group I (mild or
      less degree) and group II (moderate degree) and group II (serious degree). The
      Pittsburgh sleep quality index (PSQI) were compared before and after treatment in
      the 3 groups, and between two groups after treatment. Results There were
      significant differences in the therapeutic effect as the groups I, II compared
      with the group III (P < 0.01). The total sleep quality in the group I was better
      than that in the group II (P < 0.05). CONCLUSION: The degree of anxiety and
      depression in the patient of insomnia is one of important factors influencing
      therapeutic effect of acupuncture on insomnia.

PMID- 16570440
TI  - [Observation on therapeutic effect of warming needle moxibustion on knee
      osteoarthritis of deficiency-cold type].
AB  - OBJECTIVE: To compare clinically therapeutic effects of warming needle
      moxibustion and simple acupuncture on knee osteoarthritis. METHODS: One hundred
      and twenty cases conformed with the diagnostic criteria of knee osteoarthritis
      with TCM kidney-yang deficiency and cold syndrome were randomly divided into a
      warming needle moxibustion group and a simple acupuncture group. Guanyuan (CV 4),
      Qihai (CV 6), Zusanli (ST 36) and others were selected in the two groups. Their
      therapeutic effects were assessed with joint pain scale, knee osteoarthritis
      severity index scale and cold syndrome differentiation factors. RESULTS: Both
      warming needle moxibustion and simple acupuncture could alleviate pain of knee
      osteoarthritis, improve dysfunction of the knee joint, reduce symptoms. The
      clinically basic cured rate and the total effective rate were 32.1% and 96.4% in
      the warming needle moxibustion group, which were better than 7.4% and 92.6% in
      the simple acupuncture group. CONCLUSION: Warming needle moxibustion is an
      effective therapy for knee osteoarthritis with kidney-yang deficiency and cold
      type.

PMID- 16570441
TI  - [Clinical observation on treatment of rheumatoid arthritis with cake-separated
      mild moxibustion combined with Western medicine].
AB  - OBJECTIVE: To observe the effect-increasing action of cake-separated mild
      moxibustion on rheumatoid arthritis (RA), and to probe a new method for RA.
      METHODS: Sixty cases were randomly divided into 2 groups. The control group
      (n=30) were treated with oral administration of methotrexate (MTX) as basic
      treatment, and non-steroid anti-inflammatory agents (NSAIDs) according to
      conditions of the patient. The treatment group (n=30) were treated with the same
      treatment as the control group, and Fuzi case-separated moxibustion at Guanyuan
      (CV 4) and Zusanli (ST 36) was added. They were treated for 3 months. RESULTS:
      After treatment of 3 months, the total effective rate was 83.3% in the treatment
      group, which was higher than 60.0% in the control group (P < 0.05); there were
      significant differences before and after treatment in all indexes in the two
      groups (P < 0.05 or P < 0.01); the ratio of the patients who completely withdrew
      NSAIDs in the treatment group was significantly higher than that in the control
      group (P < 0.05); the rate of adverse reaction in the treatment group was
      significantly lower than that in the control group (P < 0.05). CONCLUSION: Fuzi
      cake-separated mild moxibustion can increase clinical therapeutic effect on RA
      and reduce dosage of NSAIDs.

PMID- 16570442
TI  - [Controlled observation on catgut implantation at acupoint for treatment of
      prolapse of lumbar intervertebral disc].
AB  - OBJECTIVE: To compare therapeutic effects of catgut implantation at acupoint and
      routine acupuncture on prolapse of lumbar intervertebral disc. METHODS: One
      hundred and forty cases were randomly divided into a treatment group and a
      control group, 70 cases in each group. The treatment group were treated with
      catgut implantation at acupoint, once each week, 3 sessions constituting one
      course, and the control group with routine acupuncture, once every other day, 10
      sessions constituting one course. RESULTS: The effective rate was 95.6% after
      treatment of one course and 88.2% 3 months later in the treatment group, which
      were better than 84.6% and 72.3% in the control group, respectively (Both P <
      0.05). CONCLUSION: Catgut implantation at acupoint has a better therapeutic
      effect on prolapse of lumbar intervertebral disc, with lower cost.

PMID- 16570443
TI  - [Observation on therapeutic effect of blood-letting puncture combined with
      electroacupuncture on muscular pulling injury].
AB  - OBJECTIVE: To observe the role of blood-letting puncture in the treatment of
      muscular injury. Methods One hundred and six cases with pulling injury of
      hamstring muscles were randomly divided into a treatment group and a control
      group. The treatment group (n=55) were treated by electroacupuncture combined
      with blood-letting puncture at Ashi points on the injury part. The control group
      (n=51) were treated with simple electroacupuncture. RESULTS: Both the 2 groups
      were effective. There was no significant difference between the 2 groups in the
      therapeutic effect for the patient with a duration of illness of 1-14 days; but
      for the patient with the duration of illness of over 14 days, the treatment group
      was better than the control group (P < 0.05). For the patient with simple injury
      of the belly of muscle, the treatment group was better than the control group (P
      < 0.05). CONCLUSION: Blood-letting puncture combined with electroacupuncture in
      the therapeutic effect on muscular pulling injury is superior to the control
      group, with treatment advantages for the patient with longer duration of illness
      and simple injury of belly of muscle.

PMID- 16570444
TI  - [Clinical observation on chiropractics combined with acupuncture at Sifeng (EX-UE
      10) for treatment of infantile anorexia].
AB  - OBJECTIVE: To search for an effective therapy for infantile anorexia. METHODS:
      Sixty-two cases of infantile anorexia were randomly divided into a treatment
      group and a control group, 31 cases in each group. The treatment group were
      treated with chiropractics plus acupuncture at Sifeng (EX-UE 10), and the control
      group with oral administration of zinc gluconate granules made by the
      pharmaceutical factory of the hospital, for 2 weeks. RESULTS: The effective rate
      was 93.5% in the treatment group, which was better than 74.2% in the control
      group (P < 0.05); there were significant differences in blood zinc content and
      urinary amylase activity in the two groups before and after treatment (P < 0.01),
      with more significant increase in the treatment group as compared with the
      control group (P < 0.05). CONCLUSION: Chiropractics combined with acupuncture at
      Sifeng (EX-UE 10) has a better therapeutic effect on infantile anorexia.

PMID- 16570445
TI  - [Effects of wrist-ankle acupuncture on functional states of the vegetative nerve
      in the recruit].
AB  - OBJECTIVE: To observe effects of wrist-ankle acupuncture on functional states of
      the vegetative nerve in the recruit. METHODS: Sixty recruits with the vegetative
      nerve balance index y > +0.56 determined with "Wenger-Chong Zhong Zhong Xiong"'s
      vegetative nerve balance factor assay were randomly divided into a treatment
      group and a control group. The treatment group were treated with wrist-ankle
      acupuncture and the control group with nothing. RESULTS: After treatment, 24
      cases with y < +0.56 was found in the treatment group and 16 cases in the control
      group with a significant difference between the two groups (P < 0.05).
      CONCLUSION: Wrist-ankle acupuncture can better improve functional state of the
      vegetative nerve in the recruit.

PMID- 16570446
TI  - [Observation on activating effectiveness of acupuncture at acupoints and non
      acupoints on different brain regions].
AB  - OBJECTIVE: To probe the theoretical basis of acupuncture by investigating the
      relationship of 'true' acupuncture and 'sham' acupuncture, with the cerebral
      functions observed by means of functional magnetic resonance imaging (fMRI).
      METHODS: Eighteen healthy volunteers with normal vision were randomly divided
      into group A and B. Firstly, all the volunteers received 'sham' acupuncture, and
      then acupuncture was given at Guangming (GB 37) and Taichong (LR 3) in the group
      A, and Fenglong (ST 40) and Xiangu (ST 43) were given in the group Activation in
      the thalamus, B.A 1.5 Tesla Vision Scanner (Siemens, Erlangen) was used for
      imaging. RESULTS: Activation in the thalamus, the red nucleus, the sulcus
      lateralis and the parieto-temporal cortex proved that there was a significant
      difference between true acupuncture and sham acupuncture in the GLM test.
      CONCLUSION: Acupuncture does not have effects on the visual cortex, but it has
      active action on the insula sulcus lateralis and the parieto-temporal cortex,
      which are involved in painful and somatosensory stimulation.

PMID- 16570447
TI  - [Controlled observation on effects of different needle retaining time in scalp
      acupuncture on motor function in the infant of cerebral palsy].
AB  - OBJECTIVE: To compare therapeutic effects of different needle retaining time in
      scalp acupuncture on motor function in the infant of cerebral palsy. METHODS:
      Randomized controlled design and Jin three needle therapy were used, and the
      therapeutic effects of needle retaining time of 1 h and 30 min on cerebral palsy
      were compared. RESULTS: After treatment for 2 months, the improvement of motor
      function in the group of retaining needle of lh was better than that in the 30
      min group. CONCLUSION: Prolonging the retaining needle time for sufficient
      stimulation amountis an important factor for achieving a better therapeutic
      effect in scalp acupuncture treatment of infant cerebral palsy.

PMID- 16570448
TI  - [Observation on therapeutic effects of bird-pecking needling and needle warming
      moxibustion on bulging of lumbar intervertebral disc].
AB  - OBJECTIVE: To explore the best manipulating method for bulging of lumbar
      intervertebral disc. METHODS: Eighty cases were randomly divided into a treatment
      group (n=58) and a control group (n=22). The treatment group were treated with
      bird-pecking needling and needle warming moxibustion, and the control group with
      needle warming moxibustion of uniform reinforcing and reducing method. Their
      therapeutic effects were compared. RESULTS: The total effective rate was 100.0%
      in the treatment group and 81. 8% in the control group with a significant
      difference between the two groups (P < 0.01). CONCLUSION: Therapeutic effects of
      bird-pecking needling and needle warming moxibustion on bulging of lumbar
      intervertebral disc is significantly superior to that of needle warming
      moxibustion of uniform reinforcing and reducing method.

PMID- 16570449
TI  - [Effect of pricking blood therapy at Ashi points on peripheral pain mediums in
      the acute gouty arthritis rat].
AB  - OBJECTIVE: To study the analgesic mechanism of pricking blood therapy at Ashi
      points in the acute gouty arthritis rat. METHODS: Forty rats were randomly
      divided into a blank group, a model group, an indomethacin group and a pricking
      blood group. Except the blank group, other groups were injected with sodium urate
      liquor into the ankle cavity to develop the acute gouty arthritis rat model, and
      the indomethacin group received gastric perfusion of indomethacin, and the
      pricking blood group were treated with pricking blood therapy at Ashi points. The
      peripheral pain mediums K+, NE, DA, (5-HT contents were determined. RESULTS: The
      K+, DA, 5-HT contents in the pricking blood group decreased significantly as
      compared with the model group (P < 0.01, P < 0.05); there was no significant
      difference in the content of NE between the pricking blood group and the model
      group. CONCLUSION: Pricking blood at Ashi points can effectively inhibit release
      of the peripheral pain mediums K+, DA and 5-HT.

PMID- 16570450
TI  - [Effects of acupuncture on ET mRNA expressions in different brain regions of the
      rat of experimental cerebral bleeding].
AB  - OBJECTIVE: To probe into the mechanism of acupuncture for treatment of cerebro
      cardiac syndrome. METHODS: The rats were randomly divided into a normal group, a
      sham operation group, a cerebral bleeding group, an acupuncture group and an
      acupuncture control group. The acupuncture group were treated with acupuncture at
      "Neiguan" (PC 6), "Shuigou" (GV 26), "Renying" (ST 19), and the acupuncture
      control group with acupuncture at "Shenmen" (HT 7) and "Danzhong" (CV 17). The
      tissue in situ hybridization technique was used to detect dynamic changes of
      endothelin (ET) mRNA expression in both the central cardiovascular special
      regulative area and the myocardium, and imaging quantitative analysis on the
      positive response materials was carried out. RESULTS: The experimental cerebral
      bleeding could rapidly induce abnormal expression of ET gene in the cerebral
      bleeding surrounding area, hypothalamus, brain stem, hippocampus and myocardium.
      Up-regulation of FT mRNA expression could be found at 6 h of cerebral bleeding,
      and it reached to the peak at 24 h, and slightly reduced at 72 h, still being
      higher than the normal level. At the same time, ET expression in the myocardium
      increased. Acupuncture could block the increase of FT gene expression induced by
      cerebral bleeding. CONCLUSION: Acupuncture exerts protective action on injuries
      of neurons and myocardium induced by cerebral bleeding via blocking the increase
      of FT gene expression induced by cerebral bleeding.

PMID- 16570451
TI  - [Acupuncture at five Shu points for treatment of 126 cases of numbness of hands
      and feet induced by peripheral diabetic neuropathies].
AB  - OBJECTIVE: To observe therapeutic effect of acupuncture on peripheral diabetic
      neuropathies in the African area. METHODS: Five Shiu points on the four limbs
      were selected. Jing (well-point) was needled by pricking method for blood
      letting, and acupuncture was given at points Xing (spring-point), Shu (stream
      point), Jing (river-point) and He (sea-point), and after arrival of qi, the
      needles were retained for 30 min, once every other day, for 2 therapeutic
      courses. RESULTS: Forty-five cases were markedly effective and 68 cases were
      effective, the total effective rate being 89.68%. CONCLUSION: Acupuncture has
      obvious therapeutic effect on diabetic neuropathies in the African area.

PMID- 16570452
TI  - [Advances of studies on traditional moxibustion therapy for treatment of cancer].
AB  - In recent years, the studies on moxibustion for treatment of cancer are
      increasing day by day, with some advances. In the paper, clinical and
      experimental studies on traditional moxibustion for treatment of cancer and the
      mechanisms are reviewed, and some problems and shortcomings are put forward.

PMID- 16570453
TI  - Sialology, and who owns saliva anyway?

PMID- 16570454
TI  - Salivary diagnostics: the future is now.

PMID- 16570455
TI  - To probe or not to probe.

PMID- 16570456
TI  - Informed consent.

PMID- 16570457
TI  - Risk versus cost?

PMID- 16570458
TI  - Practice implications.

PMID- 16570459
TI  - Locating pain.

PMID- 16570460
TI  - Oral brush biopsies.

PMID- 16570461
TI  - Minimally invasive dentistry.

PMID- 16570462
TI  - Response from the AAP.

PMID- 16570463
TI  - Conclusions questioned.

PMID- 16570464
TI  - Salivary diagnostics powered by nanotechnologies, proteomics and genomics.
AB  - BACKGROUND: The ability to monitor health status, disease onset and progression,
      and treatment outcome through noninvasive means is a highly desirable goal in
      health care promotion and delivery. Oral fluid is a perfect medium to be explored
      for health and disease surveillance. METHODS: Two prerequisites exist before the
      goal of salivary diagnostics can be achieved: identification of specific
      biomarkers associated with a health or disease state and the development of
      technologies that can discriminate between the biomarkers. A recent initiative of
      the National Institute of Dental and Craniofacial Research has created a roadmap
      to achieve these goals through the use of oral fluids as the diagnostic medium to
      scrutinize the health and/or disease status of patients. This is an ideal
      opportunity to optimize state-of-the-art saliva-based biosensors for salivary
      biomarkers that discriminate between diseases. RESULTS: Seven technology groups
      are developing point-of-care salivary diagnostic technologies. Three groups are
      working together toward deciphering the salivary proteome. CONCLUSION: These
      collective efforts and the convergence of salivary diagnostic technologies and
      the salivary proteome will present unparalleled opportunities to explore the
      diagnostic potential of saliva for oral and systemic diseases.

PMID- 16570465
TI  - Salivary biomarkers of existing periodontal disease: a cross-sectional study.
AB  - BACKGROUND: The authors conducted a study to determine if salivary biomarkers
      specific for three aspects of periodontitis--inflammation, collagen degradation
      and bone turnover--correlate with clinica features of periodontal disease.
      METHODS: The relationship between periodontal disease and the levels of
      interleukin-1 beta (IL-1beta), matrix metalloproteinase (MMP)-8, and
      osteoprotegerin (OPG) in whole saliva of 57 adults (28 "case" subjects with
      moderate-to-severe periodontal disease and 29 healthy control subjects) was
      examined in a case-control trial. RESULTS: Mean levels of IL-1beta and MMP-8 in
      saliva were significantly higher in case subjects than in controls. Both analytes
      correlated with periodontal indexes, whereas, after adjustment for confounders,
      OPG did not. Elevated salivary levels of MMP-8 or IL-1beta (more than two
      standard deviations above the mean of the controls) significantly increased the
      risk of periodontal disease (odds ratios in the 11.3-15.4 range). Combined
      elevated salivary levels of MMP-8 and IL-1beta increased the risk of experiencing
      periodontal disease 45-fold, and elevations in all three biomarkers correlated
      with individual clinical parameters indicative of periodontal disease.
      CONCLUSION: Salivary levels of MMP-8 and IL-1beta appear to serve as biomarkers
      of periodontitis. CLINICAL IMPLICATIONS: Qualitative changes in the composition
      of salivary biomarkers could have significance in the diagnosis and treatment of
      periodontal disease.

PMID- 16570466
TI  - Geriatric alcoholism: pathophysiology and dental implications.
AB  - BACKGROUND: The authors reviewed the clinical features, epidemiology, diagnosis,
      medical treatment, orofacial findings and dental treatment of geriatric patients
      with alcoholism. TYPES OF STUDIES REVIEWED: The authors conducted MEDLINE
      searches for the period 1995 through 2004 using the terms "alcoholism,"
      "geriatric," "pathophysiology," "treatment" and "dentistry." They selected
      reports published in English in peer-reviewed journals for further review.
      RESULTS: Physiological changes associated with aging permit the harmful effects
      of drinking alcohol to arise at lower levels of consumption than in younger
      people. Excessive use of alcohol exacerbates the medical and emotional problems
      associated with aging and predisposes the person to adverse drug reactions with
      medications controlling these illnesses. CLINICAL IMPLICATIONS: The incidence of
      dental disease in this population is extensive because of diminished salivary
      flow and a disinterest in performing appropriate oral hygiene techniques.
      Concurrent abuse of tobacco products worsens dental disease and heightens the
      risk of developing oral cancer. Identification of patients who abuse alcohol, a
      cancer-screening examination, preventive dental education, and use of saliva
      substitutes and anticaries agents are indicated. Clinicians must take precautions
      when performing surgery and when prescribing or administering analgesics,
      antibiotics or sedative agents that are likely to have an adverse interaction
      with alcohol.

PMID- 16570467
TI  - Efficacy of an early intervention for patients with acute temporomandibular
      disorder-related pain: a one-year outcome study.
AB  - BACKGROUND: The authors conducted a randomized clinical trial to evaluate the
      efficacy of a biopsychosocial intervention for patients who were at high risk
      (HR) of progressing from acute to chronic temporomandibular disorder (TMD)
      related pain. METHODS: The authors classified subjects' risk using a predictive
      algorithm and randomized them into an early-intervention (EI) or a
      nonintervention (NI) group. The EI included cognitive behavioral skills training
      and biofeedback. The authors assessed pain and psychosocial measures at intake
      and at a one-year follow-up. Subjects' self-reported pain levels were measured on
      an analog scale and as a response to palpation. RESULTS: At one year, EI-group
      subjects had significantly lower levels of self-reported pain and depression. At
      one year, more NI-group subjects than EI-group subjects had utilized health care
      for jaw-related pain. NI-group subjects were 12.5 times as likely to have a
      somatoform disorder, more than seven times as likely to have an anxiety disorder,
      and 2.7 times more likely to have an affective disorder at one year, compared
      with EI-group subjects. CONCLUSIONS: EI-group subjects had reduced pain levels,
      improved coping abilities and reduced emotional distress at one year. CLINICAL
      IMPLICATIONS: The TMD-related pain experience is complex and requires early
      identification with a biopsychosocial EI to achieve maximal, sustainable results.

PMID- 16570468
TI  - Primary, secondary and tertiary treatment of dental caries: a 20-year case
      report.
AB  - BACKGROUND: This case report follows the 20-year clinical treatment of a patient
      at high risk of developing dental caries. The author describes the treatment of
      the primary and permanent dentitions. CASE DESCRIPTION: The author describes the
      use of primary, secondary and tertiary measures to treat caries in a high-risk
      patient. He emphasizes the need for long-term care to monitor disease activity
      and describes the use of in-office tests for estimating Streptococcus mutans
      levels. This case illustrates the episodic nature of the caries process in which
      caries activity is related to risk factors, and the treatment regimen varies from
      tooth to tooth. CONCLUSION AND CLINICAL IMPLICATIONS: This case report documents
      the use of the medical paradigm in the treatment of dental caries, as well as the
      surgical paradigm as an important component of treatment.

PMID- 16570469
TI  - Exposure to bisphenol A from bis-glycidyl dimethacrylate-based dental sealants.
AB  - BACKGROUND: Bisphenol A (BPA) is a common component of composites and dental
      sealants. The potential exists for human exposure after sealant placement.
      METHODS: The authors prospectively enrolled 15 men in an exposure assessment
      study; 14 completed the study. After placement of clinically appropriate amounts
      of one of two sealants, the authors measured BPA in saliva and urine samples
      collected at prescribed intervals after the sealants were placed. They used
      selective and sensitive isotope-dilution mass-spectrometry-based methods for BPA
      measurements, thus providing the most reliable results. RESULTS: Helioseal F
      (Ivoclar Vivadent, Amherst, N.Y.) leached negligible amounts of BPA. Urinary and
      salivary BPA levels in subjects who received these sealants were similar to
      baseline levels. Delton Light Cure (LC) Opaque pit-and-fissure sealant
      (Dentsply/Ash, York, Pa.) leached more BPA, resulting in low-level BPA exposures
      similar to those used in laboratory animal testing. BPA exposure after Delton LC
      sealant placement was significantly higher than exposure after placement of
      Helioseal F. Patients treated with Delton LC had significantly higher doses of
      BPA (110 microg) than did those treated with Helioseal F (5.5 microg) (P <
      .0001). CONCLUSIONS: Placement of clinically relevant amounts of Delton LC
      sealant resulted in low-level BPA exposure; however, exposure was negligible
      after placement of Helioseal F. Saliva collection after sealant placement likely
      reduced systemic absorption of BPA from dental sealants. Sealants should remain a
      useful part of routine preventive dental practice, especially those that leach
      negligible amounts of BPA. CLINICAL IMPLICATIONS: Dental sealants may be a point
      source for low-level BPA exposure at levels that show health effects in rodents.
      Further research is required to determine whether human exposure to BPA at these
      levels causes adverse effects.

PMID- 16570470
TI  - Measuring the validity of two in-office water test kits.
AB  - BACKGROUND: The authors conducted a study to determine the validity of two
      commercially available in-office water test kits compared with a spread plate
      technique using the gold standard dehydrated culture medium R2A agar for
      monitoring the quality of dental treatment water. METHODS: Over a 12-week period,
      one author monitored nine dental units in a dental school that each were equipped
      with an independent water reservoir. The author collected 351 split samples,
      cultured them using three test methods, counted bacterial colonies manually and
      assessed validity using two cutoff values: < or = 200 colony-forming units per
      milliliter (CFU/mL) (an American Dental Association goal) and < or = 500 CFU/mL
      (a Centers for Disease Control and Prevention [CDC] recommendation and a U.S.
      Environmental Protection Agency [EPA] mandate). RESULTS: Of the 351 split samples
      processed, the in-office test kits' accuracy ranged from 25 to 69 percent,
      according to the ADA and CDC/EPA recommendations, compared with the R2A agar.
      CONCLUSIONS: Overall, the in-office test kits underestimated bacteria levels,
      producing inaccurate measurements of bacterial levels compared with the R2A agar.
      CLINICAL IMPLICATIONS: The data suggest that use of the two in-office test kits
      could result in a lack of compliance, owing to underestimating bacterial
      contamination with recognized recommendations for dental unit waterline quality.

PMID- 16570471
TI  - The military oral health care system as a model for eliminating disparities in
      oral health.
AB  - BACKGROUND: Healthy People (HP) 2010 is a national health promotion and disease
      prevention initiative of the U.S. Department of Health and Human Services. The HP
      2010 report highlighted a range of racial/ethnic disparities in dental health. A
      substantial portion of these disparities appear to be explained by differences in
      access to care. Members of the U.S. military have universal access to care that
      also has a compulsory component. The authors conducted a study to investigate the
      extent to which disparities in progress toward achievement of HP 2010 objectives
      were lower among the military population and to compare the oral health of the
      military population with that of the civilian population. METHODS: The
      participants in this study were non-Hispanic white and non-Hispanic black males
      aged 18 to 44 years. They were drawn from the Tri-Service Comprehensive Oral
      Health Survey (10,869 including 899 recruits who participated in the TSCOHS
      Recruit Study) and the Third National Health and Nutrition Examination Survey
      (4,779). RESULTS: We found no disparities between black and white adults in
      untreated caries and recent dental visit rates in the military population.
      Disparities in missing teeth were much lower among military personnel than among
      civilians. CONCLUSIONS: A universal access-to-care system that incorporated an
      aspect of compulsory treatment displayed little to no racial disparity in
      relevant oral health outcomes. This demonstrates that it is possible for large,
      diverse populations to have much lower levels of disparities in oral health even
      when universal access to care is not provided until the patient is 18 or 19 years
      of age.

PMID- 16570472
TI  - Increasing prevalence of emergency department visits for pediatric dental care,
      1997-2001.
AB  - BACKGROUND: Hospital emergency department (ED) visits for non-urgent care have
      been increasing since the late 1950s. This study investigated the prevalence and
      characteristics of pediatric ED visits for dental problems during a five-year
      period. METHODS: This retrospective study included newborns through 17-year-olds
      with dental complaints identified from the electronic register of the ED of Texas
      Children's Hospital, Houston, between January 1997 and December 2001. The authors
      described patient characteristics, diagnoses, factors associated with ED use for
      nontraumatic problems and annual changes in ED visits for dental and nondental
      complaints. RESULTS: Of the 1,102 subjects, 809 (73.4 percent) had nontraumatic
      and 293 (26.6 percent) had traumatic dental complaints. The study revealed a 121
      percent increase in ED visits for dental complaints and a 66-fold increase in
      admissions between 1997 and 2001. Of the inpatient admissions, 68 percent were
      the result of caries and its sequelae. CONCLUSIONS: This study revealed a
      substantial increase in ED visits and hospital admissions for dental problems
      during the study period. The majority of dental problems were nontraumatic in
      nature. PRACTICE IMPLICATIONS: Dental care experts should be available in ED
      settings in which increases in such visits are seen. Studies must be conducted to
      explore ways of keeping patients from seeking care in EDs inappropriately.

PMID- 16570473
TI  - The 'mini'-implant has arrived.
AB  - There is no question that dental implants have been the most influential change
      in dentistry during the last half-century. In general, they are well-proven and
      highly useful. However, the diameter of standard implants (approximately 3.75
      mm), along with the frequent need to graft bone to allow for their placement,
      have limited their use for those who most need implants. The introduction,
      approval and continuing observation of success of smaller-diameter mini-implants
      have stimulated use of implants in situations in which standard-sized implants
      could not have been used without grafting. The result has been more patients who
      have been served successfully at reduced cost with minimized pain and trauma-
      patients who could not have been treated with implants otherwise. Continuing
      research is needed for further verification of the acceptability of mini
      implants.

PMID- 16570474
TI  - Conflict resolution.
AB  - The sooner conflict is identified and confronted, the more quickly it can be
      resolved (and the sooner, the better). When this is accomplished calmly and
      objectively, many areas of conflict will be eliminated. Addressing conflict as it
      arises also sends a clear message to the team that the practice seeks resolution,
      not punishment or negative consequences. In addition, the dentist and the office
      manager need to lead by example by avoiding gossip and encouraging open
      communication. The goal is to go from a parent-child relationship with the dental
      team to an adult-adult relationship using this series of managerial conflict
      resolution steps.

PMID- 16570475
TI  - Is there civil liability under HIPAA?

PMID- 16570476
TI  - When is it proper to refer a patient receiving public aid to another dentist?

PMID- 16570477
TI  - For the dental patient. Toothbrush care, cleaning and replacement.

PMID- 16570478
TI  - 40 million US teenagers!

PMID- 16570480
TI  - A 17-month-old boy with fever of unknown origin.

PMID- 16570479
TI  - Managing adolescents.
AB  - The goal of this issue is to encourage the pediatrician to view these sensitive
      health issues from many different angles so that the effects on the adolescent's
      life can be better appreciated. The initial step involves effectively engaging
      the patient to unmask the concerns and then providing the optimal available
      treatment.

PMID- 16570482
TI  - Effective interviewing and counseling of the adolescent patient.
AB  - A vast number of successful recommendations are available to physicians who want
      to learn how to strengthen their interactions with adolescent patients.
      Understanding that the physician-patient relationship is dynamic is the first
      step toward building a strong repertoire within this patient sample. Therefore,
      physicians may assume that adolescent perceptions of the physician-patient
      relationship and the services provided will change as they change developmentally
      or as the situation is modified. Finding a balance between family and patient
      concerns while gaining increased experience with skills less-practiced (eg,
      communication about sensitive topics) will improve adolescent perceptions of your
      expertise, knowledge, and abilities. Finally, following up on changes across time
      in adolescents' concerns, perceptions, abilities, and the physician-patient
      relationship itself, will help to ensure continued satisfaction and service use
      by adolescents and their families.

PMID- 16570481
TI  - A 7-year-old girl with back pain and inability to walk.

PMID- 16570483
TI  - Acne: improving skin and self-esteem.
AB  - Many safe and effective treatments are available to the acne sufferer. The
      clinician is encouraged to offer treatment to the adolescent with a face full of
      pimples, even if not asked for by the patient, as psychosocial underpinnings may
      be present but not obvious on examination. Obvious physical benefits will result,
      but psychosocial improvements also may occur.

PMID- 16570485
TI  - Adverse consequences of tattoos and body piercings.
AB  - Body piercings and tattoos are becoming more common in the adolescent population
      today. Despite their movement into mainstream society, literature to aid in
      counseling of teens about these issues is scant. The practitioner dealing with
      this population of patients must be armed with the information necessary that
      will help adolescents make informed decisions about tattoos and piercings.

PMID- 16570484
TI  - The obese adolescent.
AB  - Childhood obesity is one of the formidable challenges that healthcare providers
      face. Early recognition and implementation of preventive strategies is crucial in
      combating this problem. Inculcation of a healthy lifestyle in our youth by
      encouraging physical activity, decreasing sedentary pastimes, and making healthy
      food choices is critical right from the start, before poor habits become
      ingrained. More research is needed to find more effective ways to treat obesity
      in childhood and adolescence.

PMID- 16570486
TI  - Adolescent drug & alcohol use in the 21st century.
AB  - Screening for drug abuse should be a part of adolescent health maintenance
      visits. Good interviewing skills using open-ended, nonjudgmental questions in a
      private setting may elicit a history of drug abuse. A detailed and comprehensive
      history is important to recognize family dynamics, early behavioral changes
      (Table 5, see page 198), comorbid psychiatric conditions, and the adolescent's
      attitude toward substances of abuse. A good physical exam may reveal clinical
      sequelae of drug abuse. Testing for drug abuse should be done with the patient's
      consent except in cases where judgment is impaired. Periodic screening for drugs
      is a part of drug treatment and rehabilitation. The typical pediatrician is not
      equipped to provide drug counseling and treatment to the abusing adolescent.
      Specialized referral centers would be ideal, and clinicians need to be aware of
      local resources in their communities. Anticipatory guidance explaining the ill
      effects of drugs is mandatory. Prevention should be aimed at increasing public
      awareness of the consequences of drug abuse, improving parenting techniques, and
      introducing school-based drug prevention programs. The fight against substance
      abuse needs to be a community effort in which the individual, the family and the
      primary care physician play important roles.

PMID- 16570488
TI  - Motivation and goal setting theory.

PMID- 16570487
TI  - The adolescent with a chronic illness.
AB  - The primary care clinician can play an important role in enhancing the quality of
      life for the adolescent with chronic illness through developmentally appropriate,
      individualized and compassionate coordination of care (Sidebar 2). Special
      attention to the process of adolescence, family, and psychological issues are
      required for successful management. Transition of care to adult services should
      be planned carefully with a multidisciplinary team.

PMID- 16570489
TI  - 2006 coding update--part II.

PMID- 16570490
TI  - Thinking strategically about imaging capacity and capital.
AB  - Diagnostic imaging continues to place high demands on hospital and health system
      capital budgets due to the high cost of most equipment and the rate of
      technological change. Diagnostic imaging also can be a significant service in
      competitive positioning, both alone and in conjunction with other programs and
      services. The purpose of this article is to provide a framework for linking
      diagnostic imaging to key hospital programs, and for forecasting future demands
      and capital requirements. The model has been developed over time in a number of
      settings in the United States and Canada. The specific examples are mostly from
      the Seton Healthcore Network in Austin, TX.

PMID- 16570491
TI  - Using STAT properly.
AB  - The misuse of the term STAT has long been a problem in many hospitals. Instead of
      being the universal word for "immediate," it has become a convenient phrase used,
      in some cases, to get what the physician wants now. Although the principles of
      this article may be applied to many modalities in the healthcare field, this
      article deals solely with portable chest x-rays performed at the University of
      Minnesota Medical Center, Fairview in Minneapolis. The diagnostic radiology
      department performed a 2-week analysis of orders in August 2004. The results
      showed that 74% of all portable chest x-rays were ordered as STAT. The manager,
      along with a staff radiologist, then created a list of clinical reasons that were
      appropriate for STAT, ASAP, or Routine orders. Then, there was a 2-week period of
      time delegated for education, during which the list was brought to the nurse
      managers of several patient care areas as well as some chief residents at the
      university's medical school. These individuals then shared the list with their
      staff. A second analysis conducted in November 2004 showed that an 11% decrease
      had been achieved. Given that 20,000 portable chest x-rays are performed at the
      medical center annually, the figure represents a 2,200 reduction in STAT
      portables per year. With the success of this endeavor, the radiology department
      piloted a second program to further decrease the number of STAT orders. Since the
      radiology department was using computed radiography (CR) and a picture archiving
      and communication system (PACS), research began to unearth the response times.
      The idea was to advertise to physicians how fast they could get their images,
      using the theory that if the times were quick enough, perhaps there would less of
      a tendency to order STATs. The results showed that a STAT order could be
      completed and viewable on PACS in an average of 17 minutes, and an ASAP in 28
      minutes. A poster advertising these response times was generated and distributed
      to the nurse managers and residents to post in the inpatient units. The poster
      was well received. A two-week survey conducted in March 2005 showed that STATs
      now accounted for 54% of the portable chest x-rays. With this two-pronged
      approach, the radiology department was able to decrease the number of portable
      chest X-rays by 20%. Another 2-week survey conducted in May 2005 showed that
      number of portable chest x-rays ordered as STAT declined further to 52%.

PMID- 16570492
TI  - Maximizing the imaging center revenue cycle: the billing process.

PMID- 16570493
TI  - Medical archiving: solutions for medical image management.
AB  - Within the field of radiology, innovations in digital imaging have led to the
      development of the picture archival and communication system (PACS), which is now
      a part of the fundamental technological infrastructure supporting radiology
      practice in the digital age. Healthcare providers like hospitals, outpatient
      centers, and clinics are facing an explosion of medical imaging content as the
      industry continues the transfer from film to digital format. As a result,
      providers need to rethink their storage architecture strategies to better address
      the varied applications of the modern healthcare organization. Digital medical
      images are typically very large and technological advances are constantly
      increasing the rate at which such data is being recorded, image volume can
      present a storage capacity challenge. In addition, the images must be safely
      stored for a long time and easy to access. Regardless of strategy, the continued
      deployment of PACS as the primary vehicle to streamline medical imaging workflow,
      manage image access and increase user productivity is important. Grid computing,
      typically associated with the capture of idle computational cycles on
      heterogeneous servers, employs computing techniques that can offer providers
      unique solutions to their storage problems.

PMID- 16570494
TI  - Chewbacca, we've made the jump to light speed...

PMID- 16570495
TI  - Patient safety: a collaborative, blame-free, team approach.
AB  - Establishing a comprehensive radiology patient safety program can help organize
      and focus patient safety efforts system-wide. This article highlights the process
      followed in creation of a comprehensive radiology patient safety program at
      Partners HealthCare System. The key to comprehensive patient safety is talking
      about errors that happen, learning from them and preventing them from happening
      again. At Partners, a collaborative, blame-free, team approach is the answer.

PMID- 16570496
TI  - E-mail use in the radiology workplace.
AB  - E-mail is a wonderful tool. But, like any tool, it can be misused. The proper use
      of e-mail by an administrator, manager, or technologist can provide a wonderful
      communication tool not just for customers and colleagues. Bulk e-mail-especially
      those developed in HTML, which can include visually appealing fonts and graphics
      has an unrealized potential in radiology. Just be sure it doesn't qualify as the
      hated "spam," or important colleagues and customers will feel abused rather than
      helped. Finally, use words and phrases in an e-mail that can enhance
      collaboration and build positive relationships. E-mail can help win friends and
      influence others in meaningful and positive ways. It can be a useful strategy to
      facilitate positive interactions and gain support.

PMID- 16570497
TI  - New Year's resolutions.

PMID- 16570498
TI  - Turf wars.

PMID- 16570499
TI  - Recent developments in the treatment of atherosclerosis.
AB  - Atherosclerosis is one of the most frequent causes of cardiac arrest. The major
      cause of this disease is high concentrations of lipid in the blood. Medicinal
      agents so far have been quite successful in the management of hyperlipidemia.
      Among the several widely used drugs, (fibrates, statins and niacin) statins are
      the most frequently prescribed in many forms of hyperlipidemia. Recently, statins
      have been found to produce serious toxicities, which are rare but can be
      potentially harmful and are noise concern for the immediate need to develop some
      new chemical entities in this category. This review is primarily concerned with
      recent developments in atherosclerotic drug discovery including novel inhibitors
      of cholesterol biosynthesis, cholesterol absorption inhibitors and antioxidants.
      The review also focuses on possible future targets including gene therapy.

PMID- 16570500
TI  - New natural urease inhibitors from Ranunculus repens.
AB  - Phytochemical investigations on the chloroform and ethyl acetate soluble
      fractions of the roots of Ranunculus repens led to the isolation of methyl 3,4,5
      trihydroxybenzoate 1, R(+)- 4-methoxydalbergione 2 and R(+)-dalbergiophenol 3.
      The structures of these compounds were established through spectral studies
      including 1D and 2D NMR experiments and by comparison with literature data. These
      compounds showed potent inhibitory activity against urease.

PMID- 16570501
TI  - Antiinflammatory and antioxidant evaluation of novel coumarin derivatives.
AB  - Several coumarin derivatives have been reported to present multiple biological
      activities and especially antiinflammatory/antioxidant activities. Recently the
      synthesis and in vivo/in vitro anti-inflammatory/antioxidant activities of
      several new coumarin derivatives with a 7-azomethine linkage have been reported.
      In the present study these derivatives were further tested for their antioxidant
      ability. Some of them were found in vitro to inhibit lipid peroxidation and to
      strongly scavenge superoxide radicals. Compound 3 was found to potently inhibit
      cyclooxygenase-1 (COX-1) and the yeast-induced rat paw oedema. The most active
      compounds within the set were tested against adjuvant-induced arthritis. Compound
      3 was found to significantly protect the rats from adjuvant-induced arthritis
      (when it is administered from the first day or when it is administered the
      fourteenth day, with the first symptoms of the disease). An attempt was made to
      delineate the possible mechanism of action of the studied compounds.

PMID- 16570502
TI  - Syntheses and spectroscopic characterization of some phosphoramidates as
      reversible inhibitors of human acetylcholinesterase and determination of their
      potency.
AB  - The ability of phosphoramidates Me2NP(O)(Cl)(p-NHC6H4NO2) 1, Me2NP(O)(p
      NHC6H4NO2)2 2, (CH3C6H4O-p)P(O)(p-NHC6H4NO2)2 3 and (CH3C6H40-p)2P(O)(p
      NHC6H4NO2) 4 to inhibit human acetylcholinesterase (hAChE) has been evaluated by
      a modified Ellman's method and spectrophotometric measurements. Results showed
      that compounds 1 and 2 do not have any inhibitory potency, whereas compounds 3
      and 4 were reversible mixed inhibitors. The IC50 values for inhibitors 3 and 4
      were 0.143 and 0.581 mM, respectively. The previously unknown compounds 3 and 4
      were synthesized and characterized by 1H, 13C, 31P NMR and IR spectroscopy and
      elemental analysis.

PMID- 16570503
TI  - Oxovanadium(IV) complexes of hydrazides: potential antifungal agents.
AB  - Oxovanadium(IV) -derived antifungals have been prepared by condensing equimolar
      amounts of vanadyl sulfate with hydrazides. All the synthesized ligands and their
      metal complexes were characterized by IR, UV-Visible and micro analytical data.
      These synthesized compounds were screened for their antifungal activity against
      Aspergillus flavus (A. flavus), Trichophyton longifusus (T. longifusus), Candida
      albicans (C. albicans), Microsporum canis (M. canis), Fusarium solani (F. solani)
      and Candida glaberata (C. glaberata) fungal strains. All complexes showed
      promising antifungal activity against different fungal strains with the exception
      of F. Solani and C. glaberata. Minimum Inhibitory Concentration (MIC) of
      different complexes and ligands are in the range of 250 to 400 microg/mL. Complex
      7a and ligand 13 exhibit lowest MIC of 250 microg/mL whereas, complex 5a and
      ligands 2, 7 and 14 showed highest MIC of 400 microg/mL.

PMID- 16570504
TI  - Status of some free radical scavenging enzymes in the blood of myocardial
      infarction patients.
AB  - Pro-oxidant and anti-oxidant systems and their levels have significant roles in
      occlusive vascular diseases. In the present communication, we have measured the
      levels of some representative anti-oxidant enzymes in the blood of the patients
      of myocardial infarction after reperfusion and compared them to age and sex
      matched healthy persons. Our findings show that the activities of anti-oxidant
      enzymes (viz. SOD, catalase and glutathione reductase) are significantly
      decreased whereas there is significant increase in the levels of
      malonaldialdehyde (a marker of free radical-mediated damage) in the patients. The
      findings point out that ischemic myocardial disorders are associated with
      excessive free radical generation and free radical-mediated damage of lipids.

PMID- 16570505
TI  - Interaction of 3-hydroxybenzoate-6-hydroxylase with cibacron blue.
AB  - Cibacron blue is a potent inhibitor of 3-HBA-6-hydroxylase at a concentration < 1
      microM. Kinetic analyses revealed that at a concentration below 0.5 microM the
      dye behaves as an uncompetitive inhibitor with respect to 3-HBA and competes with
      NADH for the same site on the enzyme. The alteration of the near-UV CD spectrum
      and quenching of the emission fluorescence of the enzyme by cibacron blue
      indicates a significant alteration in the environment of aromatic amino acid
      residues due to a stacking interaction and subtle conformatiodnal changes in the
      enzyme. The concentration-dependent quenching of the intrinsic fluorescence of
      the enzyme by cibacron blue was employed to determine the binding parameters such
      as association constant (Ka) and stoichiometry (r) for the enzyme-dye complex.

PMID- 16570506
TI  - Inhibition kinetics of hydrogen peroxide on beta-n-acetyl-D-glucosaminidase from
      prawn (Penaeus vannamei).
AB  - The effects of hydrogen peroxide (H2O2) on prawn NAGase activity for the
      hydrolysis of pNP-beta-D-GlcNAc have been studied. The results show that H2O2 can
      reversible inhibit the enzyme (IC50 = 0.85 M) and the inhibition is of a mixed
      type. The kinetics show that k+o is much larger than k+0, indicating the free
      enzyme is more susceptible than the enzyme-substrate complex in the H2O2
      solution. It is suggested that the presence of the substrate offers marked
      protection against inhibition by H202. Changes of activity and conformation of
      the enzyme in different concentrations of H202 have been compared by measuring
      the fluorescence spectra and residual activity and show that the change of
      conformation is more rapidly than that of the residual activity, which implies
      that the whole conformation of the enzyme changes more rapidly than the
      conformation of the active centre of the enzyme in the H2O2 solution.

PMID- 16570507
TI  - Characteristics of rabbit muscle adenylate kinase inhibition by ascorbate.
AB  - Earlier studies [1-3] showed that of the glycolytic enzymes, the muscle isozymes
      PFK-1, LDH, and AK were inhibited by ascorbic acid. These studies on the
      characteristics of the inhibition of RMAK by ascorbate are part of a hypothesis
      [3] that ascorbate facilitates the storage of skeletal muscle glycogen by
      inhibiting glycolysis when the muscle is at rest. These studies examine
      conditions for RMAK inhibition, prevention of inhibition, and reversal of
      ascorbate inhibition. We found that the concentration of RMAK was an important
      condition for inhibition. Above 200 nM RMAK, inhibition by ascorbate could not be
      demonstrated and below that concentration RMAK became increasingly sensitive to
      ascorbate inhibition. Associated with increased sensitivity to inhibition by
      ascorbate is a deviation from a linear to a concave relationship between low RMAK
      concentrations and enzyme activity. At low RMAK concentrations, the concave
      relationship becomes convex in the presence of muscle aldolase. In addition,
      aldolase reverses inhibitions by ascorbate. A comparison of inhibition of RMAK
      byascorbate and inhibition of LDH-m4 [3] is discussed. Other proteins prevent
      RMAK inhibition but do not reverse inhibition by ascorbate. The role of RMAK as a
      factor in the control of the rate of glycolysis is presented as is the role of
      compartmentalization with respect to the proposed role for ascorbate inhibition.

PMID- 16570509
TI  - In vitro effects of some drugs on human red blood cell glucose-6-phosphate
      dehydrogenase enzyme activity.
AB  - In vitro effects of omeprazole, morphine sulphate, remifentanyl, ketamine and
      vankomycin were investigated on human red blood cell glucose-6 phosphate
      dehydrogenase (G-6PD) (E.C. 1.1.1.49) enzyme activity purified from human red
      blood cell by 2', 5'ADP-Sepharose 4B affinity gel. The obtained I50 values of
      omeprazole, morphine, remifentanil, ketamine and vankomycin were 3.24, 43.58,
      97.6, 64.16 and 0.903 mM, respectively and the Ki constants for omeprazole,
      morphine and vankomycin were 8.22 +/- 2.055, 25.93 +/- 6.482, and 2.71 +/- 0.677
      mM, respectively and they were non competitive inhibitors.

PMID- 16570508
TI  - Thymidine phosphorylase from Escherichia coli: tight-binding inhibitors as enzyme
      active-site titrants.
AB  - Thymidine phosphorylase (EC 2.4.2.4) catalyses the reversible phosphorolysis of
      pyrimidine 2'-deoxynucleosides, forming 2-deoxyribose-1-phosphate and pyrimidine.
      5-Chloro-6-(2-imino-pyrrolidin-1-yl)methyl-uracil hydrochloride (TPI, 1) and its
      5-bromo analogue (2), 6-(2-amino-imidazol-1-yl)methyl-5-bromo-uracil (3) and its
      5-chloro analogue (4) act as tight-binding stoichiometric inhibitors of
      recombinant E. coli thymidine phosphorylase, and thus can be used as the first
      active-site titrants for it using either thymidine or 5-nitro-2'-deoxyuridine as
      substrate.

PMID- 16570510
TI  - In vitro effect of schistosomicidal drugs on hepatic arylsulfatase B from the
      schistosoma-infected mouse.
AB  - Arylsulfatase B (ASB) hydrolyzes the desulfation of N-acetylgalactosamine-4
      sulfate at the non-reducing terminal of glycosaminoglycans. This enzyme activity
      was found to be elevated in mice schistosomiasis. In the present study, the
      catalytic and immunological properties of purified ASB from the liver of
      Schistosoma-infected mouse was investigated in the presence and absence of the
      schistosomicidal drugs praziquantel and Commiphora extract. The in vitro effect
      of praziquantel was found to be inhibitory with a Ki value of 5.5 x 10(-4) M
      while that of commiphora extract was as an activator. Furthermore, these drugs
      did not have an observed effect on the immunological properties of ASB with
      regard to its binding to its polyclonal rabbit antibody. These results indicate
      that some schistosomicidal drugs may reverse the alteration of the catalytic
      properties of the enzyme in schistosomiasis.

PMID- 16570511
TI  - Potent inhibition of fatty acid synthase by parasitic loranthus [Taxillus
      chinensis (dc.) danser] and its constituent avicularin.
AB  - The medicinal herb parasitic loranthus in a screen was found to inhibit fatty
      acid synthase (EC 2.3.1.85, FAS) and reduce body weight of rats in our previous
      study. Now we have determined the inhibitory characteristics and kinetic
      parameters of extracts of parasitic loranthus [Taxillus chinensis (DC.) Danser].
      The parasitic loranthus extracts (PLE) inhibits FAS reversibly and irreversibly
      and with an IC50 value of 0.48 microg/ml, appears to be the most potent inhibitor
      reported to date. PLE contains various potent inhibitors and may react with
      different sites on FAS. The irreversible inhibition exhibits a time-dependent
      biphasic process including a speedy fast-phase during the initial several
      minutes. The fast-phase inhibition seems to be caused by some potent but low
      concentration component(s) in the extracts. In addition, we have found that
      avicularin existing in this herb can potently inhibit FAS. This glycosylated
      flavonoid and quercetin play an effective role in inhibiting FAS by parasitic
      loranthus.

PMID- 16570512
TI  - In vitro antibacterial, antifungal & cytotoxic activity of some
      isonicotinoylhydrazide Schiff's bases and their cobalt (II), copper (II), nickel
      (II) and zinc (II) complexes.
AB  - Isonicotinoylhydrazide Schiff's bases formed by the reaction of substituted and
      unsubstituted furyl-2-carboxaldehyde and thiophene-2-carboxaldehyde with
      isoniazid and, their Co (II), Cu (II), Ni (II) and Zn (II) complexes have been
      synthesized, characterized and screened for their in vitro antibacterial activity
      against Mycobacterium tuberculosis, Escherichia coli, Klebsiella pneumoniae,
      Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi, Shigella
      dysenteriae, Bacillus cereus, Corynebacterium diphtheriae, Staphylococcus aureus
      and Streptococcus pyogenes bacterial strains and for in vitro antifungal activity
      against Trichophyton longifusus, Candida albicans, Aspergillus flavus,
      Microsporum canis, Fusarium solani and Candida glabrata. The results of these
      studies show the metal complexes to be more antibacterial and antifungal against
      one or more bacterial/fungal strains as compared to the uncomplexed compounds.
      The brine shrimp bioassay indicated Schiff's bases, L3 and L6 and, their Cu (II)
      and Ni (II) metal complexes to be cytotoxic against Artemia salina, while all
      other compounds were inactive (LD50 > 1000).

PMID- 16570513
TI  - Anticholinesterase activity of some major intermediates in carbacylamidophosphate
      synthesis: preparation, spectral characterization and inhibitory potency
      determination.
AB  - Carbacylamidophosphates with the general formula RC(O)NHP(O)R1R2 constitute
      organophosphorus compounds that are used as insecticides, pesticides and ureas
      inhibitors. In this work, we studied the inhibition potency of CCl3
      C(O)NHP(O)Cl21, CHCl2C(O)NHP(O)Cl(2)2, CH2ClC(O)NHP(O)Cl23 and
      CF3C(O)NHP(O)Cl(2)4, which are the major intermediates for
      carbacylamidophosphates synthesis towards human erythrocyte acetylcholinesterase
      (hAChe) activity using Ellman's modified kinetic method. Unexpectedly, it was
      observed that they were not only hydrolytically unstable but also inhibited hAChE
      in a similar manner to that produced by organophosphorus insecticides. Enzymatic
      data, bimolecular inhibition rate constants (ki) and IC50 values for inhibition
      of hAChE demonstrated that they are irreversible inhibitors and the inhibition
      potency of compound 2 (IC50 = 88 microM) was the greatest in comparison with
      compounds 1, 3 and 4. Also the electropositivity of the phosphorus atom and the
      hydrophobicity of the compounds demonstrated that these two factors play an
      additional effect and different role in the inhibitory activity of these
      compounds. Hydrolytic stability of the compounds was determined by 31P NMR
      monitoring of the loss of the parent molecules with D2O as a function of time.
      This study considers antiacetylcholinesterase activity according to the
      structural and the electronic aspects of compounds 1-4, according to IR, 1H, 13C
      and 31P NMR spectral data.

PMID- 16570514
TI  - Synthesis and cytotoxic and analgesic activities of some 1, 5-diaryl-3
      ethoxycarbonylpyrrole derivatives.
AB  - Some 1,5-diaryl-3-ethoxycarbonyl-2-methylpyrrole derivatives were obtained by
      reacting 1-aryl-3-ethoxycarbonylpent-1,4-diones and a suitable aniline derivative
      or sulfanilamide under Paal-Knorr pyrrole synthesis conditions. The cytotoxicity
      of the compounds was tested and all compounds, except for compound 2 h, showed a
      time-dependent increase in cytotoxic activity. Analgesic activities of the
      compounds were determined by using the tail-flick and tail-immersion methods;
      some of the compounds showed potent analgesic activity.

PMID- 16570515
TI  - Inhibition of rat liver and kidney arginase by cadmium ion.
AB  - Cadmium ion activates arginase from many species of organisms but is an inhibitor
      of arginase from many other species. The purpose of this study was to investigate
      the inhibition of rat liver and kidney arginase by cadmium ion. Rat kidney
      arginase was inhibited by much lower concentrations of cadmium ion than rat liver
      arginase. Cadmium ion was a mixed noncompetitive inhibitor of both rat liver and
      kidney arginase. Cadmium ion enhanced the substrate activation of rat kidney
      arginase while still inhibiting the enzyme. Cadmium ion prevented the substrate
      inhibition of rat kidney arginase by fluoride while still inhibiting the enzyme.
      Cadmium ion also inhibited rat kidney arginase in the presence of manganese ion.

PMID- 16570516
TI  - Spirituality, psychiatry and participation: a cultural analysis.
AB  - This article begins by asking whether religion and spirituality are useful terms
      for cross-cultural comparisons. After discussing the increasing distinction
      between religion and spirituality in Western cultures, it points out how the
      terms religion and spirituality are used in divergent ways in the literature and
      the need for conceptual clarification in this area. Broadly, spirituality relates
      to interconnectedness, ultimate meaning or life force itself. The current use of
      the term spirituality in Western cultures derives both from Christian
      spirituality and 'New Age' thinking, which often appropriates ideas from Eastern
      religious traditions. The sociocultural roots of this division are complex,
      involving both growth of individualism, the pursuit of meaning and discontent
      with materialism and scientific rationalism. This situation is contrasted with
      other monotheistic religions where there is no distinction between religion and
      spirituality. This turn to spirituality has influenced health care professionals'
      conceptualizations of health and healing. The implications for psychiatry are
      discussed. I conclude that spirituality is a way of 'being in the world' and
      shares affinities with Tambiah's notion of a participatory mode of thinking.

PMID- 16570517
TI  - Detachment: gateway to the world of spirituality.
AB  - Mystical states are common cross-culturally. Here we examine the prevalence and
      general characteristics of these states. We then proceed to critically examine
      the theories purporting to explain these states: psychoanalytic, cognitive and
      neurobiological, all of which attempt to explain the breakdown of the boundaries
      between the self and external world. We conclude by exploring the implications of
      mystical states for cultural psychiatry.

PMID- 16570518
TI  - Spiritist views of mental disorders in Brazil.
AB  - The Spiritist perspective on mental disorders exerts a great influence in Brazil.
      Spiritist theory supports the survival of the spirit after death with an exchange
      of knowledge between the incarnated and disincarnated spirits. This article
      reviews the texts on mental disorders and Spiritism written by four leading
      Spiritist authors: Allan Kardec, Bezerra de Menezes, Inacio Ferreira and Joanna
      de Angelis. These authors advocated a model of spiritual etiology without
      rejecting the biological, psychological, and social causes of mental disorders.
      The Spiritist etiologic model for mental disorders includes the negative
      influences of discarnated spirits (termed 'obsession') or trauma experienced in
      previous lives. In addition to conventional medical and psychological
      therapeutics, spiritist seances for disobsession are recommended, as well as
      'passes', prayers and efforts to live according to ethical principles. The
      importance of Spiritist views in Brazil indicates the need for more academic
      research on this tradition.

PMID- 16570519
TI  - Religious stigmata, magnetic fluids and conversion hysteria: one survival of
      'vital force' theories in scientific medicine?
AB  - A study of Natuzza Evolo, a contemporary Roman Catholic stigmatic in southern
      Italy, raises certain questions of mechanism and evidence. Was this a miracle,
      hysterical conversion or contrived? The medical interpretation of the phenomenon
      as conversion disorder raises questions about the popularity of hysteria as a
      medical diagnosis and the ways in which it functions like 'vital force', as a
      metaphoric mediator between the natural world, human agency, and the ultrahuman.

PMID- 16570520
TI  - Schizophrenic consciousness, spiritual experience, and the borders between
      things, images and words.
AB  - A prototypical feature of schizophrenic consciousness is that it undergoes a
      solidification of the imaginary space in which mental events take place. The
      bipartition between images and 'real' things is jeopardized and imagination is
      transformed into 'physical' forms. Parallel to this solidification of imaginary
      space in schizophrenic consciousness, more generally the rigid tripartite
      separation of things, images and words upon which the spatial order of
      consciousness is founded starts to erode. I explore different spiritual and
      philosophical traditions which shed light on and make more understandable the
      schizophrenic consciousness that call into question this separatedness. I argue
      that these traditions indicate that our current commonsensical approach to the
      separatedness between things, images and words is historically and culturally
      determined.

PMID- 16570521
TI  - Spirituality and treatment choices by South and East Asian women with serious
      mental illness.
AB  - The purpose of this qualitative study is to investigate how South and East Asian
      immigrant women who have diagnoses of serious mental illness make treatment
      choices in relation to spirituality and to explore how gender, cultural beliefs,
      and spirituality intersect with the process of choice. The findings reveal that
      the process of spiritual choice includes three interrelated phases: (1)
      identifying contributing factors, (2) exploring spiritual resources and
      strategies, and (3) living with the choices. Variations among health beliefs and
      health care decisions are explained and services that women see as being helpful
      are identified.

PMID- 16570522
TI  - Religious practice and psychological distress: the importance of gender,
      ethnicity and immigrant status.
AB  - The present study examined the relationship between religious practice and
      psychological distress in a culturally diverse urban population to explore how
      religious affiliation, gender, ethnicity, and immigrant status affect this
      relationship. Data were drawn from a study of health care utilization in
      Montreal. A stratified community sample of 1485 yielded four religious groups:
      Protestant (n = 205), Catholic (813), Jewish (201), and Buddhist (150), and a
      group with no declared religion (116). The sample was composed of five
      ethnocultural groups: Anglophone Canadian-born, Francophone Canadian-born, Afro
      Caribbean, Vietnamese, and Filipino immigrants. Psychological distress was
      assessed with the 12-item version of the General Health Questionnaire (GHQ).
      Religious involvement was measured with three items: 1) declared religion; 2)
      frequency of attendance at religious meetings; and 3) frequency of religious
      rituals performed at home. Multiple regression models examined the relationship
      of religious practice to distress, controlling for sociodemographic variables
      including ethnicity. Overall, attendance at religious services was associated
      with a lower GHQ score. Attendance at religious services also was inversely
      related to psychological distress for females, Protestants, Catholics, Filipinos,
      and Afro-Caribbeans; but not for males, Buddhists or Jews. Religious practice at
      home was not associated with level of distress for any group. The 'no declared
      religion' group had the highest mean GHQ score of all the groups. Results confirm
      the association between attendance at religious services and lower levels of
      distress, but reveal ethnospecific and gender effects indicating the need to
      understand the impact of religious practice on mental health in social and
      cultural context.

PMID- 16570523
TI  - A pilot clinical study of continuous intravenous ascorbate in terminal cancer
      patients.
AB  - Case studies suggest that vitamin C, given intravenously at doses of 10-100
      grams/day can improve patient well being and in some cases, reduce tumor size.
      While ascorbate is generally considered safe, clinical data on high intravenous
      doses is limited. Twenty-four late stage terminal cancer patients were given
      continuous infusions of 150 to 710 mg/kg/day for up to eight weeks. Blood
      chemistry and blood count profiles were obtained at roughly one-week intervals
      while patient health, adverse events and tumor progression were monitored. The
      majority of patients were vitamin C deficient prior to treatment. Intravenous
      infusions increased plasma ascorbate concentrations to a mean of 1.1 mM. The most
      common adverse events reported were nausea, edema, and dry mouth or skin; and
      these were generally minor. Two Grade 3 adverse events 'possibly related' to the
      agent were reported: one patient with a history of renal calculi developed a
      kidney stone after thirteen days of treatment and another patient experienced
      hypokalemia after six weeks of treatment. White blood cell counts were stable
      while hemoglobin and hematocrit levels dropped slightly during treatment,
      consistent with trends observed prior to therapy. Blood creatinine, BUN, glucose,
      and uric acid concentrations decreased or remained stable during therapy,
      suggesting that ascorbate infusions did not adversely affect renal function. One
      patient had stable disease and continued the treatment for forty-eight weeks.
      These data suggest that intravenous vitamin C therapy for cancer is relatively
      safe, provided the patient does not have a history of kidney stone formation.

PMID- 16570524
TI  - [Knowledge on polypharmacy in a group of 65-year-old people or older living in a
      sector of the metropolitan area of Puerto Rico].
AB  - Addressing the high utilization of medications among the elderly, this study
      explored the degree of knowledge of polypharmacy and its consequences, as well as
      the pattern of utilization by a group of elders 65 years of age and over in the
      San Juan metropolitan area of Puerto Rico. A dual technique was utilized: focus
      groups and a survey. Two focus groups were performed in order to explore issues
      pertaining the following domains: quality of life, doctor-patient and pharmacist
      patient relationships, degree of knowledge of polypharmacy, and need of
      information. A questionnaire was administered to obtain information regarding
      their pattern of drug utilization. Results of focus groups indicated that the
      elderly have learned how to cope with their chronic conditions and be able to
      continue with quality of life. Additionally, results suggested a need form the
      elderly to develop more assertiveness and closeness with their health care
      providers, both doctor and pharmacist; as well as a lack of sufficient knowledge
      of the serious implications that polypharmacy brings. Results from the survey
      revealed and confirmed their inappropriate utilization of medications, and
      suggest that this segment consults multiple physicians, all of which may bring
      potential problems of adverse drug interactions. Further investigation is needed
      to examine fully the issue of polypharmacy, as well as the need of education that
      results in empowerment of patients, families and communities.

PMID- 16570525
TI  - Eye diseases in Puerto Rico.
AB  - OBJECTIVE: To report on the major causes of eye diseases leading to visual
      impairment and blindness in a sub-urban population in Puerto Rico. DESIGN: A
      population-based study of eye diseases in Puerto Ricans living in the San Juan
      metropolitan area of Puerto Rico. PARTICIPANTS: Nine thousand two hundred ninety
      eight patients aged from 40 to 79 years-of-age from the San Juan metropolitan
      area. METHODS: A chart review of 9,298 patients was done. Patients carrying
      diagnosis such as cataracts, glaucoma, age-related macular degeneration (ARMD),
      and diabetic retinopathy were evaluated. Descriptive statistics and chi square
      analysis were used to evaluate findings. RESULTS: 2,056 patients out of 9,298 had
      cataracts (22.1%); 3,963 patients (42.6%) had glaucoma; 199 patients had ARMD
      (2.1%); and 700 patients (7.5%) had diabetic retinopathy. The prevalence of
      cataracts was higher in the population study than in the Hispanic population of
      the Los Angeles Latino Eye Study (LALES) (p<0.001). The prevalence of glaucoma
      was higher in our patients than in Hispanic population studied by the LALES
      (p<0.0001). The prevalence of ARMD and the prevalence of diabetic retinopathy was
      lower than expected when compared to Hispanic population of LALES study (p<0.0001
      in both instances). CONCLUSIONS: In this population-based study, the prevalence
      of cataracts and glaucoma was higher than the results found in the Hispanic
      populations reported in the LALES. However, in our study, we found a lower
      prevalence of ARMD and diabetic retinopathy. Various factors may lead to this
      significant difference in the prevalence of eye diseases between the PR
      population and Hispanic population in the continental USA. Further studies are
      needed to evaluate the prevalence of eye diseases in Puerto Rico.

PMID- 16570527
TI  - Effectiveness in the implantation of law 155 of 2002 ordering the designation of
      spaces for breastfeeding in government agencies.
AB  - As part of an effort to promote and protect breastfeeding among working mothers
      in Puerto Rico, Public Law 427 was passed in December 2000. This law grants a
      paid breastfeeding daily break for milk extraction in the workplace. In support
      of this initiative Public Law 155 was passed in 2002 ordering Secretaries,
      Directors, Presidents and Public Administrators of the government of Puerto Rico
      to designate breastfeeding spaces in the workplaces. OBJECTIVE: Describe the
      level of compliance with the dispositions of Law 155 in government agencies.
      METHODOLOGY: A cross sectional descriptive study was carried out. A sample of 28
      government agencies was randomly selected, representing 25% of the total number
      of agencies, and a structured telephone interview was administered using an
      instrument made up of 6 premises. RSEULTS: All (100%) of the agencies had
      knowledge about the existence of this law, but only 50% had set up and equipped
      the spaces. Of these, all had a table, a chair, and an electric outlet, 43% had
      available running water, and 71% provided a refrigerator for milk storage. Fifty
      three percent of the agencies reported having received followup communications to
      verify whether they were complying with the law, and 61% reported having a
      written public policy in support of breastfeeding for working mothers. Only 54%
      of the agencies stated they had offered some type of orientation to their women
      employees regarding their breastfeeding rights. CONCLUSIONS: In spite of over two
      years since the passing of Law 155, the majority of government agencies in Puerto
      Rico have not complied with its legal dispositions. It is necessary that the
      responsible entities watch for the satisfactory compliance with this law since
      working mothers need a secure and accesible place for milk extraction during the
      working day.

PMID- 16570526
TI  - General anesthesia: as a challenge and treatment need option in pediatric
      dentistry.
AB  - OBJECTIVE: The purpose of this study was to determine the type and
      characteristics of the interventions, indications of dental treatment and
      procedures performed to patients treated under general anesthesia (GA) by
      pediatric dentistry residents, during the 1997-1999 period. METHOD: A sample of
      57 hospital records of patients treated as part of the Special Pediatric Course
      at the Puerto Rico Pediatric Hospital were reviewed. Statistical analysis was
      done using the chi-square test for inferences on proportions. RESULTS: MR
      patients made up 59.7% and NMR patients made up 40.3% of the sample studied. Ages
      ranged from 2 to 35 years with a mean age of 11 years (SD=8.54). MR patients were
      classified into 7 categories: mental retardation (38.2%), cerebral palsy (14.7%),
      epileptic (5.9%), mental syndromes (26.9%), hydrocephalic (5.9%), autism (5.9%)
      and others (2.9%). The NMR were classified into 5 categories: early childhood
      caries (65.2%), cardiac patients (8.7%), maxillofacial anomalies (4.3%), organic
      syndromes (13.1%) and others (8.7%). The dental procedures performed were: dental
      extractions 84%(MR) and 68% (NMR), restorative procedures 87.3%(MR) and
      12.7%(NMR). Oral prophylaxis was performed in 76.8%, fissure sealants in 10.7%
      and topical fluoride applications in 21.8%. CONCLUSION: Dental extraction was a
      frequently performed procedure in both groups. The prevalence of exodontia and
      restorative procedures indicates the need to design and implement prevention
      programs for special pediatric patients.

PMID- 16570528
TI  - Pilot study of the differences among the Puerto Rican aged by gender in opinion,
      attitude and exposure to abuse, mistreatment and neglect.
AB  - OBJECTIVES: Contribute to the knowledge base of the risk factor literature by
      gender for abuse, mistreatment and neglect of the Puerto Rican aged. BACKGROUND:
      A review of the literature in Puerto Rico and the United States related to gender
      impacting upon elder abuse, mistreatment and neglect report conflicting findings.
      METHODS: A 107 item questionnaire was developed. The definitions of abuse,
      mistreatment and neglect were based on those set out by the National Center on
      Elder Abuse in the United States (1998). The questionnaire has been preliminarily
      validated by Cronbach's Alpha .879. The sample of respondents was based upon
      availability. This method was selected in the face of practical considerations in
      spite of criticism to the external validity that this type of sample represents.
      Structured face to face interviews were carried out from August to December 2004
      with 430 aged residing in community. Data were entered into the SPSS program
      whereby cross tabulations were carried out for gender. RESULTS: Elderly Puerto
      Ricans regardless of gender are knowledgeable concerning what constitutes
      attributes of abuse, mistreatment and neglect. Females were found to report a
      high percentage of yes responses than males to opinion statements related to
      situations of abuse, mistreatment and neglect. Males reported a higher percentage
      of yes responses to situations of exposure to abuse and neglect than females.
      CONCLUSIONS: Findings here are similar to some reported in the United States but
      are dissimilar to those reported in Puerto Rico. Further research must be carried
      out to pinpoint the living arrangements situations placing the aged in greatest
      risk for abuse and neglect. Such findings have implications for social policy,
      prevention and intervention strategies.

PMID- 16570529
TI  - Advances in spinal cord repair techniques.
AB  - Daily US accidents result annually in over 20,000 cases of traumatic spinal cord
      injury associated with complete and permanent paraplegias and quadriplegias
      frequently associated chronic pain. This amounts to new annual health care a
      costs of dollar 3.2 billion, and a total annual cost for all such individuals in
      the US of dollar 96 billion. Tens of thousands of additional people suffer lesser
      degrees of permanent debilitating lost spinal cord function. To help these people
      recover neurological functions, and simultaneously reduce the enormous suffering,
      and the associated medical expenses, requires developing techniques that induce
      the regeneration of lesioned adult human spinal cord axons. A number of
      techniques lead to varying degrees of axon regeneration and neurological recovery
      in the rat, but the recovery is invariably limited. While other approaches show
      potential, they have not led reliable neurological recovery. Most spinal cord
      repair techniques cannot be applied clinically because they require materials
      that are not FDA-approved. However, several FDA-approved materials are available
      that hold great promise for inducing axon regeneration, especially when used
      simultaneously. Here we review efforts to induce the regeneration of spinal cord
      axons, how what is known about promoting regeneration of axons across peripheral
      nerve gaps may be applied to repairing spinal cord lesions, and finally, how
      several readily available materials may induce axons to regenerate in the spinal
      cord and restore neurological function.

PMID- 16570530
TI  - Risk stratification in the patient with non ST segment elevation acute coronary
      syndrome.
AB  - Patients hospitalized with unstable angina (UA) or with a non-ST segment
      elevation myocardial infarct (NSTEMI) are at increased risk of suffering
      refractory angina, recurrent myocardial infarct (MI), and death. These patients
      need to be evaluated more aggressively. According to the last published
      guidelines (2002) of UA/NSTEMI by the ACC/AHA Task Force, these patients should
      be categorized in a risk scale as: low, intermediate or high. This should be done
      in the initial evaluation, which includes: medical history, physical exam, an
      electrocardiogram (ECG) and cardiac markers. The TIMI risk score should also be
      used as complementary in this risk assessment. High risk patients, without
      contraindications, should be managed more aggressively with coronary angiography.
      On the other end, low risk patients, and some intermediate, may be evaluated more
      conservatively with early non-invasive studies for further assessment of ischemia
      and prognosis.

PMID- 16570531
TI  - Luis Llorens Torres and the impossible return: identity, conflict and hope in the
      national poem of Puerto Rico.
AB  - The psychodynamic exploration of the content of literary works and of the
      personal lives of their authors oftentimes reveals how they can be mutually
      reflective of the other. Such is the case of the poem, "Valle de Collores" (The
      Valley of Collares), considered by many to be the national poem of Puerto Rico
      and of the author Luis Llorens Torres (1876-1944), regarded as the "Poet Laureate
      of Puerto Rico." The timelessness and wide appeal of certain literary works has
      been attributed, among other reasons, to the fact that they address universal
      inner conflicts that affect all human beings. The poem "Valle de Collores" is the
      narrative of a country boy who leaves home to face the larger world and, as he
      reaches adulthood, he looks back and expresses his impossible longing to return
      to the rural home of his childhood. It is a description of the universal
      struggles of human development and of separation-indi-viduation, loss and
      mourning and a longing to return, and a wish to merge with the early parental
      objects of childhood. The poem also parallels the history of the Puerto Rican
      people, in their transition from a rural society under Spanish rule to an
      industrialized society as an American Commonwealth. This difficult transition
      resulted in a massive immigration of Puerto Ricans to the United States that
      continues to this day. The poem also represents the longing of many Puerto Rican
      immigrants to return to their island home, and to a simpler time of more
      fundamental values. The land that is left behind and longed for becomes a
      metaphor for the early maternal imago.

PMID- 16570532
TI  - Anaplastic T-cell lymphoma presenting as fatal acute liver failure.
AB  - Acute liver failure (ALF) is an uncommon manifestation of liver disease and
      constitutes a medical emergency for which early identification is necessary.
      Hepatic involvement by hematologic malignancies although frequent, rarely causes
      severe hepatic dysfunction. Even more, acute hepatic failure as the first
      manifestation of a hematologic malignancy is extremely uncommon, although some
      cases have been reported in the literature. We describe the case of a 61 y/o
      puertorrican veteran who developed acute hepatic failure secondary to massive
      infiltration of the liver by a recurrent non-Hodgkin's lymphoma.

PMID- 16570533
TI  - [Effect of collateral circulation on myocardial protection in patients with acute
      myocardial infarction: comparison of technetium-99m-tetrofosmin myocardial single
      photon emission computed tomography and coronary angiography].
AB  - OBJECTIVES: Evaluation of myocardial blood flow from collateral vessels into the
      infarct area has been estimated by coronary angiography. In patients with acute
      myocardial infarction with Thrombolysis in Myocardial Infarction (TIMI) 0 flow,
      myocardial tracer uptake on single photon emission computed tomography (SPECT)
      images can predict the collateral blood flow in the infarct area if technetium
      (Tc)-99m-tetrofosmin was administered before recanalization. The present study
      investigated whether collateral blood flow evaluated by myocardial scintigraphy
      is a good predictor of myocardial salvage in patients with acute myocardial
      infarction. METHODS: The study group consisted of 30 patients (mean age 65 +/- 14
      years, 23 males, 7 females) with first acute myocardial infarction and coronary
      angiography evidence of total occlusion (TIMI 0) within 12 hr after the onset.
      All patients had one vessel disease related to infarction and TIMI 3 flow after
      percutaneous coronary intervention (PCI). Tc-99m-tetrofosmin was injected
      intravenously before the PCI. The regional severity score index (RSSI) was
      obtained from SPECT using the 17 segment method with the four-point scoring
      system. Myocardial viability was evaluated by the RSSI obtained from thallium
      glucose-insulin infusion SPECT after 1 week and regional wall motion score index
      obtained from echocardiography during the chronic phase. RESULTS: The patients
      were divided into two groups according to the angiographic collateral finding.
      There were no differences in RSSI on thallium-glucose-insulin SPECT and regional
      wall motion score between the good collateral group (n = 8) and poor collateral
      group (n = 22). Myocardial Tc-99m-tetrofosmin RSSI was similar in these groups.
      On the other hand, the patients were divided according to Tc-99m-tetrofosmin
      scintigraphic evaluation before PCI. RSSI on thallium-glucose-insulin SPECT was
      significantly greater (0.7 +/- 0.5 vs 1.5 +/- 0.4, p < 0.01) and regional wall
      motion score was significantly less (1.46 +/- 0.50 vs 2.08 +/- 0.78, p < 0.05) in
      the lower Tc-99m-tetrofosmin RSSI (< 1.9) group (n = 22) compared with the higher
      RSSI (> or = 1.9) group (n = 8). In addition, a significant correlation was
      obtained between Tc-99 m-tetrofosmin RSSI and regional wall motion score index (r
      = 0.53, p < 0.01). CONCLUSIONS: The collateral flow evaluated by scintigraphy was
      significantly correlated with myocardial viability.

PMID- 16570534
TI  - Relationship between lesion vessel area and myocardial salvage assessed by
      myocardial single photon emission computed tomography in acute myocardial
      infarction with stenting after thrombectomy.
AB  - OBJECTIVES: To study the relationship between lesion vessel area and myocardial
      salvage assessed by myocardial single photon emission computed tomography (SPECT)
      in acute myocardial infarction with stenting after thrombectomy. METHODS: This
      study included 71 patients who underwent stenting after thrombectomy for acute
      myocardial infarction. Intravascular ultrasound (IVUS) was performed after
      thrombectomy. Patients were classified into two groups: the High group with
      external elastic membrane cross-sectional area (EEM-CSA) of the lesion > or = 18
      mm2 (34 patients) and the Low group with EEM-CSA < 18 mm2 (37 patients). Dual
      isotope myocardial SPECT imaging was undertaken by perfusion SPECT (201Tl or
      99mTc-MIBI) and 123I-15-(p-iodophenyl)-3-(R,-S)-methylpentadecanoic acid (BMIPP).
      The image of the left ventricular myocardium was divided into 17 segments to
      calculate total defect score using a 5-grade assessment (0: normal-4: defect).
      Differences in total defect score of perfusion SPECT and 123I-BMIPP was defined
      as mismatch. RESULTS: Culprit lesion morphology was assessed by IVUS. A higher
      incidence of lipid pool-like images (47% vs 5%, p < 0.01) was observed in the
      High group. The results of myocardial SPECT study revealed no difference in the
      total defect score of 123I-BMIPP (18.3 +/- 5.5 vs 17.3 +/- 6.3 points) but the
      mismatch in total defect score of perfusion SPECT and 123I-BMIPP was
      significantly lower in the High group (3.8 +/- 3.9 vs 7.7 +/- 4.2 points, p <
      0.05). CONCLUSIONS: Patients with a high culprit lesion vessel area show fewer
      beneficial effects in myocardial salvage compared with those with low vessel area
      as assessed by myocardial SPECT in acute myocardial infarction with stenting
      after thrombectomy.

PMID- 16570535
TI  - Method analysis for optimal continuous imaging using intravascular optical
      coherence tomography.
AB  - OBJECTIVES: Optical coherence tomography(OCT)is a high-resolution imaging method
      that can clearly visualize vessels through the displacement of blood with
      flushing agents. Continuous imaging methods have not been established. This study
      investigated optimal methods for continuous OCT imaging. METHODS: Thirty-four
      arteries with stent implantation (24 peripheral and 10 coronary arteries)in 14
      pigs were examined using OCT with a motorized pullback device. Two imaging
      methods (flush alone by liquid substance and flush with occlusion) were compared.
      Adequate image acquisition was defined as the entire circumferential intimal
      layer being detectable within continuous segments. To investigate factors that
      could influence image quality, stented regions were divided into 4-5 mm segments.
      RESULTS: The flush with occlusion method provided better OCT images compared to
      flush alone (flush with occlusion: 60.9%, flush alone: 8.7%, p = 0.0002). Using
      the flush with occlusion method, the rate of adequate image acquisition was 64.4%
      and visualization of > 75% intimal circumference was 83.5%. Intravascular
      ultrasound could detect all stented regions. Segmental analyses found more
      adequate images were detected in smaller vessels (adequate segment: 3.8 +/- 0.4
      mm, inadequate segment: 4.2 +/- 0.8 mm, p < 0.0001) or with centered image wire
      position (adequate segment: center 35%, inadequate segment: center 14%, p =
      0.003). In addition, side branches did not affect image quality. CONCLUSIONS: To
      acquire continuous OCT images, the flush with occlusion method was more effective
      compared to flush alone. Moreover, image quality is affected by vessel size and
      imaging wire position. These results suggest that optimized OCT imaging can
      provide continuous vessel detection.

PMID- 16570536
TI  - Aortocoronary dissection complicated with percutaneous coronary intervention: a
      case report.
AB  - A 74-year-old female developed aortocoronary dissection during percutaneous
      coronary intervention. The forceful manipulation of the guide catheter and
      contrast medium injection seemed to be the cause of the aortocoronary dissection
      involving the coronary sinus of Valsalva. The entry of the dissection was closed
      with subsequent obliteration of the false lumen by coronary stenting under the
      guidance of intracoronary ultrasonography and angiography.

PMID- 16570537
TI  - [Persistent left ventricular systolic dysfunction in a patient with ampulla
      cardiomyopathy: a case report].
AB  - An 81-year-old woman was admitted for treatment of diastolic heart failure. Two
      weeks after admission, she suffered sudden chest pain without somatic and/or
      psychological stress. Electrocardiography showed ST elevation in leads V2- V5.
      Coronary angiography did not reveal any significant stenosis in the epicardial
      coronary artery. Left ventriculography showed apical akinesis with basal and mid
      hyperkinesis. The diagnosis was ampulla cardiomyopathy. The abnormality on
      electrocardiography was normalized 2 months later, but apical akinesis persisted
      for 1 year. Myocardial contrast echocardiography showed microvascular dysfunction
      consistent with the apical akinesis for 1 year. Microvascular dysfunction may be
      important in the pathophysiological state of ampulla cardiomyopathy.

PMID- 16570538
TI  - Acute mitral regurgitation due to ruptured chordae tendineae in a patient with
      hypertrophic obstructive cardiomyopathy: a case report.
AB  - A 63-year-old woman had been followed up for hypertrophic obstructive
      cardiomyopathy with 85 mmHg of left ventricular outflow tract pressure gradient
      over 7 years. She was hospitalized because of acute dyspnea and syncope. On
      admission, echocardiography revealed severe mitral regurgitation with ruptured
      chordae tendineae at the medial scallop of the posterior mitral leaflet. Mitral
      valve replacement was successfully performed and her symptoms improved to 28 mmHg
      of left ventricular outflow tract pressure gradient. In patients with
      hypertrophic obstructive cardiomyopathy, elevated left ventricular systolic
      pressure and systolic anterior motion of the mitral leaflets may lead to mucoid
      degeneration in the chordae tendineae. Rupture of the mitral chordae tendineae
      should be considered in the differential diagnosis of acutely deteriorated mitral
      regurgitation in patients with hypertrophic obstructive cardiomyopathy, because
      this is a rare but critical complication.

PMID- 16570539
TI  - [Abdominal aortic lesion with a systolic bruit].

PMID- 16570540
TI  - The preoperative evaluation and use of laboratory testing.

PMID- 16570541
TI  - The surgical burden: how to prevent a crisis in perioperative medicine.
AB  - Preoperative patient evaluation can minimize the surgical burden and help prevent
      a crisis in perioperative medicine. Relieving the surgical burden involves a
      shift from practicing medicine to practicing preventive care in the preoperative
      environment, as well as motivating patients to adopt healthier behaviors over the
      long term.

PMID- 16570542
TI  - Anesthetics and anesthesia techniques: impacts on perioperative management and
      postoperative outcomes.
AB  - Inhaled and intravenous anesthetic agents have diverse effects on the nervous,
      cardiovascular, and respiratory systems. Spinal and epidural anesthetics also
      produce significant physiologic changes. Some evidence points to improved
      immediate postoperative outcomes (in terms of cardiovascular outcomes, blood
      loss, and venous thromboembolism) for certain types of surgical procedures with
      epidural and spinal techniques relative to general anesthesia. Evidence is just
      beginning to emerge, however, on the relation between specific anesthetics and
      anesthetic techniques and long-term clinical outcomes. A proposed relationship
      between anesthetics, inflammation, and long-term outcomes has attracted
      increasing research interest but has yet to be well defined.

PMID- 16570543
TI  - Cardiac risk stratification before noncardiac surgery.
AB  - The history and the physical examination remain the most important elements in
      cardiac risk stratification of patients prior to noncardiac surgery. Indications
      for further cardiac tests and interventions are usually the same as in the
      nonsurgical setting. No test should be performed unless the results will affect
      patient management. In many cases, noninvasive testing is being replaced by
      prophylactic medical therapy, a topic explored in the next article in this
      supplement.

PMID- 16570544
TI  - Perioperative cardiac risk reduction: doing it right.

PMID- 16570545
TI  - Quality measurement: who is measuring outcomes and what are patients being told?
AB  - Change is inevitable, but participation is optional. An array of quality measures
      is being used by various government entities, health care purchasers and payers,
      and other groups. Many of the quality-measurement initiatives have not only
      gained the attention of large employers, but are also beginning to pique the
      public's interest. Novel approaches to measuring and rewarding quality are also
      emerging, such as pay-for-performance schemes and the use of APR-DRGs. Health
      care organizations that participate in the quality-measurement process and
      provide input will benefit by the type of measures that are ultimately created.
      It is much better to be part of the development process than to have insurer- or
      employer-designed quality measures imposed on your institution. At the very
      least, health care organizations would be wise to serve as watchdogs to ensure
      that currently proposed quality measures truly measure high-quality care.

PMID- 16570546
TI  - Preoperative pulmonary evaluation: identifying and reducing risks for pulmonary
      complications.
AB  - Postoperative pulmonary complications are among the most common sources of
      morbidity in patients undergoing major surgery. For this reason, the preoperative
      patient evaluation should emphasize risk factors for pulmonary complications as
      well as for traditional cardiac complications, as the former are comparably
      frequent and associated with longer hospital stays. Procedure-related risk
      factors are more important than patient-related risk factors for predicting
      pulmonary events, but clinicians should assess both types of factors. Pulmonary
      function testing has a limited role and should not be the basis for denying
      surgery if the surgical indication is compelling. Strategies to reduce the risk
      of postoperative pulmonary complications include optimizing management of chronic
      lung disease before surgery, lung expansion maneuvers, pain control, and
      selective placement of nasogastric tubes.

PMID- 16570547
TI  - Antibiotic prophylaxis against postoperative wound infections.
AB  - Prophylactic antibiotics should be given as close to the time of incision as
      possible to ensure that tissue antimicrobial levels are adequate and maintained
      for the duration of the procedure. The choice of antibiotic should be based on
      the organisms most likely to be encountered--usually staphylococcal skin florae.
      The choice of vancomycin over a cephalosporin may be justified in patients who
      are known carriers of MRSA. A full therapeutic dose of antibiotic should be used
      for prophylaxis. Morbidly obese patients should be given twice the standard dose.
      Redosing during an operation is recommended if the duration of the procedure
      exceeds two half-lives of the antibiotic administered. Prophylactic antibiotics
      should not continue to be administered more than 48 hours postoperatively.

PMID- 16570548
TI  - Managing perioperative risk in the hip fracture patient.
AB  - Patients with hip fracture benefit from a multidisciplinary team approach for
      preoperative and postoperative care. Team members, consisting of the orthopedic
      surgeon, internal medicine consultant, and anesthesiologist, should each have a
      role in determining a patient's readiness for surgery and communicate with one
      another about appropriate management. How urgently a hip fracture needs repair
      depends on the type of injury. In general, most injuries should be repaired as
      soon as the patient can be medically optimized (preferably 24 to 48 hours),
      keeping in mind that procedures are often lengthy and maximally invasive, and
      frequently involve complications. Nondisplaced (impacted) femoral neck fractures,
      however, should be repaired within 6 hours if possible to avert avascular
      necrosis of the femoral head and the need for total hip replacement. The
      following interventions are helpful for preventing complications following hip
      fracture repair: perioperative prophylaxis against infection.

PMID- 16570549
TI  - Perioperative management of the bariatric surgery patient: focus on cardiac and
      anesthesia considerations.
AB  - Obesity is a major public health problem in developed nations worldwide.
      Currently, the only treatment for severe obesity (BMI > or = 35 kg/m2 with
      comorbidity) that provides long-term weight loss is bariatric surgery.
      Restrictive, malabsorptive, and combination procedures have been developed. Each
      type of procedure has its merits and unique set of risks and complications.
      Weight loss after bariatric surgery is accompanied by predictable improvement or
      resolution of obesity-related comorbidities and improved quality of life and life
      expectancy. Candidates for bariatric surgery are often at high risk for
      complications because of obesity-related comorbidities. Therefore, careful
      patient selection for bariatric surgery, together with well-designed strategies
      for preventing and managing complications, are keys to success. Close monitoring
      for nutritional deficiencies and short- and long-term complications is required
      to completely assess outcomes of these procedures.

PMID- 16570550
TI  - Ambulatory anesthesia: preventing perioperative and postoperative complications.

PMID- 16570551
TI  - Evaluating postoperative fever: a focused approach.
AB  - Postoperative fever should be evaluated with a focused approach rather than in
      "shotgun" fashion. Most fevers that develop within the first 48 hours after
      surgery are benign and self-limiting. However, it is critical that physicians who
      provide postoperative care be able to recognize the minority of fevers that
      demand immediate attention, based on the patient's history, a targeted physical
      examination, and further studies if appropriate. Fever that develops after the
      first 2 days following surgery is more likely to have an infectious cause, but
      noninfectious causes that require further evaluation and treatment must also be
      considered. When evaluating postoperative fever, a helpful mnemonic is the "four
      Ws": wind (pulmonary causes: pneumonia, aspiration, and pulmonary embolism, but
      not atelectasis), water (urinary tract infection), wound (surgical site
      infection), "what did we do?" (iatrogenic causes: drug fever, blood product
      reaction, infections related to intravenous lines).

PMID- 16570552
TI  - Septic shock in the postoperative patient: three important management decisions.
AB  - The medical consultant should have a high index of suspicion for sepsis. Early
      goal-directed therapy is recommended and includes early, aggressive fluid
      resuscitation, antibiotics, and vasoactive agents, if needed. CVO2 may be helpful
      in guiding therapy, but targeting supranormal levels of oxygen delivery is not
      necessary. Empiric use of steroids and early use of activated protein C also need
      to be considered. Vasopressin should be considered if hypotension persists or if
      the situation requires escalating doses of norepinephrine.

PMID- 16570553
TI  - Optimizing postoperative pain management.
AB  - The quality of postoperative pain management can be improved. Although many safe
      and effective therapies exist, their utilization varies considerably between and
      within institutions. Major challenges include the appropriate prescribing of
      analgesic therapies and the timely response to suboptimal pain control. Patients'
      satisfaction with their analgesic care may depend less on how well their pain is
      controlled and more on the attentiveness of their caregivers.

PMID- 16570554
TI  - Nutritional issues in the surgical patient.

PMID- 16570555
TI  - Perioperative medication management: a case-based review of general principles.
AB  - Medical consultants need to recommend the safest and the most effective ways to
      manage chronic medications in the perioperative period. Outcomes data from
      clinical trials are limited in regard to perioperative medication management, so
      specific clinical trials are not available to guide decision-making in most
      circumstances. More studies in this field are needed. Communication and
      collaboration with anesthesiologists and surgeons as well as with primary care
      physicians are key to achieving optimal outcomes.

PMID- 16570557
TI  - Perioperative management of diabetes mellitus: how should we act on the limited
      evidence?
AB  - Patients with diabetes mellitus are at higher risk for complications from surgery
      than their nondiabetic counterparts. Evidence-based guidance on the perioperative
      management of diabetic patients is still very limited. Management is best guided
      by careful preoperative and postoperative consideration of diet, antidiabetic
      medication regimens, and the likelihood of specific complications of diabetes.
      Good postoperative glucose control reduces the risk of in-hospital death and
      shortens length of stay. Insulin is the mainstay of perioperative glucose
      management, and intensive insulin therapy (to a target blood glucose of 110 mg/dL
      or lower) improves a range of clinical outcomes in critically ill patients
      relative to less aggressive insulin strategies. There is little role for oral
      antidiabetic medications in the early postoperative phase.

PMID- 16570556
TI  - Preventing venous thromboembolism in surgical patients.
AB  - Hospital strategies to prevent VTE are important to reduce acute morbidity and
      mortality as well as the long-term consequences caused by venous stasis syndrome.
      Patients at low risk (eg, those who are ambulatory or undergoing a same-day
      procedure) or who are at high risk for bleeding (including those with severe
      renal impairment) are candidates for nonpharmacologic strategies for
      thromboembolic prophylaxis. Mechanical devices are effective if used
      appropriately, but compliance is a challenge. Patients who require a hospital
      stay of more than a day or two should receive a medication-based strategy,
      preferably using LMWH or fondaparinux. Patients undergoing hip replacement should
      receive extended prophylaxis with LMWH.

PMID- 16570558
TI  - Anticoagulation management strategies for patients on warfarin who need surgery.

PMID- 16570559
TI  - Perioperative care of the elderly patient.
AB  - Perioperative management is typically more complicated in older patients than in
      younger patients and requires more assessment and evaluation before surgery as
      well as precautionary steps after surgery to manage these high-risk patients.

PMID- 16570560
TI  - Optimizing the preoperative evaluation of patients with aortic stenosis or
      congestive heart failure prior to noncardiac surgery.

PMID- 16570561
TI  - Minimizing perioperative complications in patients with renal insufficiency.
AB  - Patients with an elevated serum creatinine or whose serum creatinine levels
      increase postoperatively, regardless of baseline levels, are at increased risk
      for elevated mortality. Women have a higher risk from acute renal failure than
      men at every level of serum creatinine. Acute renal failure confers an increased
      risk of mortality, chronic renal insufficiency, and postoperative infection
      independent of other postoperative complications. Preoperative measures to reduce
      risk of acute renal failure include optimizing volume and solute status, ensuring
      adequate urine flow, avoiding high doses of diuretics, optimizing hematocrit
      levels, and avoiding contrast agents.

PMID- 16570562
TI  - Pig as a favorable animal for Taenia saginata asiatica infection.
AB  - The epidemiology of Taenia saginata in some parts of Asia is confusing, in that
      beef does not appear to be the source of infection. In some areas, beef is either
      not available or not eaten raw, whereas pork at times is eaten uncooked. In light
      of this situation, we have exposed pigs and other animals to infection with
      strains of T. saginata to establish their ability to serve as intermediate hosts.
      Eggs of Taiwan Taenia, Korea Taenia, Indonesia Taenia, Thailand Taenia,
      Philippines Taenia, Ethiopia Taenia, and Madagascar Taenia were fed to 83 pigs of
      three strains: 43 Small-Ear Miniature (SEM), 34 Landrace Small-Ear Miniature (L
      SEM), and 6 Duroc-Yorkshire-Landrace (DYL). We also fed the eggs to 10 Holstein
      calves, 17 Sannean goats, and 4 monkeys (Macaca cyclopis). We succeeded in
      infecting SEM (infection rate 88%, cysticercus recovery rate 19.1%), L-SEM (83%,
      1.1%), and DYL (100%, 0.3%) pigs with Taiwan Taenia; SEM (100%, 1.7%), L-SEM
      (100%, 5.6%), and DYL (100%, 0.06%) pigs with Korea Taenia; SEM (100%, 22%) and L
      SEM (100%, 1.6%) pigs with Indonesia Taenia; SEM (75%, 0.06%) pigs with Thailand
      Taenia SEM (100%, 11%) pigs with Philippines Taenia; SEM (80%, 0.005%) pigs with
      Ethiopia Taenia; SEM (100%, 0.2%) pigs with Madagascar Taenia. Holstein calves
      became infected with Taenia from Taiwan (100%, 1.1%), Korea (100%, 0.03%),
      Thailand (100%, 0.2%), and the Philippines (100%, 6%); however, the cysticerci of
      Taenia from Korea, Thailand, and the Philippines were degenerated and/or
      calcified. Sannean goats became infected with Taenia from Taiwan (33%, 0.01%) and
      Korea (50%, 0.02%), while monkeys became infected with Taenia from Taiwan (50%,
      0.01%). However, the cysticerci were degenerated and/ or calcified. Therefore,
      these strains of pig seem to be favorable animal models for experimental studies
      of T. saginata-like tapeworms, with the SEM pig the most favorable.

PMID- 16570563
TI  - Role of TTF-1, CK20, and CK7 immunohistochemistry for diagnosis of primary and
      secondary lung adenocarcinoma.
AB  - Thyroid transcription factor-1 (TTF-1), and cytokeratin 7 (CK7) and cytokeratin
      20 (CK20) have recently been reported to be useful to distinguish between primary
      and metastatic lung adenocarcinoma. The aim of this study was to determine the
      usefulness of the staining patterns of pulmonary adenocarcinoma with antibodies
      to TTF-1, CK7, and CK20 in differentiating primary from metastatic pulmonary
      adenocarcinoma. Of the 66 lung adenocarcinoma specimens that were enrolled in our
      study, there were 40 primary lung adenocarcinomas, 12 metastatic adenocarcinomas
      from breast, 13 metastatic adenocarcinomas from colon, and 1 metastatic
      adenocarcinoma from stomach. The expression of TTF-1, CK7, and CK20 was assessed
      by immunohistochemistry. We found that 73% of primary lung adenocarcinomas
      expressed TTF-1, whereas all nonpulmonary adenocarcinomas lacked TTF-1 staining.
      CK7 expression was significantly more frequent in adenocarcinomas of pulmonary
      and breast origin than gastrointestinal (GI) origin (p < 0.001). In contrast,
      CK20 expression was significantly more prevalent in adenocarcinoma that
      originated in the GI tract than that of pulmonary or breast origin (p < 0.001). A
      combination of TTF-1+CK7+CK20- was highly significantly associated with primary
      adenocarcinoma of lung (vs GI tract, p < 0.001; vs breast, p < 0.001). A
      combination of TTF-1-CKCK20+ was highly significantly associated with
      adenocarcinoma of GI origin (vs lung, p < 0.001; vs breast, p < 0.001). Our study
      has confirmed that expression of CK7, CK20, and TTF-1 is a useful
      immunohistochemical marker for diagnosis of lung tumors and for differential
      diagnosis of primary pulmonary adenocarcinomas from extrapulmonary
      adenocarcinomas metastatic to the lung. Application of this panel of antibodies
      might be expected to increase the accuracy of diagnosis.

PMID- 16570564
TI  - Intestinal obstruction during pregnancy.
AB  - Intestinal obstruction is a rare cause of acute abdominal pain during pregnancy.
      We reviewed and analyzed the medical records of four pregnant women with
      intestinal obstruction, treated at the Department of Surgery in the Kaohsiung
      Medical University Hospital during a period of 19 years, between June 1984 and
      December 2002. Their ages ranged from 22 to 35 years (mean, 28 yrs). Three cases
      had had prior lower abdominal surgery. Adhesion was the unique finding in all
      four patients during the operation. Enterolysis was needed to release the
      intestinal obstruction in three of the patients; the fourth required resection
      and anastomosis of the ileum as a result of volvulus. Premature labor was
      prevented with tocolysis in two patients. The results of this study lead us to
      emphasize the importance of close observation and early surgery to avoid
      intestinal strangulation if a pregnant woman who develops intestinal obstruction
      has an old surgical scar on her abdomen. Premature labor may be avoided with
      tocolysis.

PMID- 16570565
TI  - The combined occluding effects of fluoride-containing dentin desensitizer and Nd
      Yag laser irradiation on human dentinal tubules: an in vitro study.
AB  - The purpose of the present study was to evaluate the combined occluding effects
      of fluoride-containing dentin desensitizer and neodymium:yttrium aluminum garnet
      (Nd-YAG) laser irradiation on human dentinal tubules. All six of the groups of
      dentin samples (A-F) included in this study received applications of fluoride
      containing dentin desensitizer. Groups B, D, and F also received Nd-YAG laser
      irradiation. Groups A and B served as controls, to allow observations of the
      occluding effects on the dentinal tubules before and after Nd-YAG laser
      irradiation. Groups C and D were treated with 0.5 M vitamin C solution, whereas
      groups E and F underwent brushing with an electric toothbrush. Scanning electron
      microscopy (SEM) revealed that the fluoridated dentinal tubule-occluding agent
      (FDTOA) formed a fine crystalline deposit on the dentin surface. After soaking in
      0.5 M vitamin C solution for 3 hours, the crystalline deposit of the FDTOA was
      completely dissolved. Furthermore, brushing of the teeth 3,600 times removed most
      of the occluding agent. When the application of FDTOA was combined with Nd-YAG
      laser irradiation, the dentin melted and then recrystallized. The occluding agent
      was thus 'burned into' the dentinal tubules, and could neither be dissolved by
      vitamin C solution nor removed by brushing. Therefore, we concluded that the
      FDTOA combined with Nd-YAG laser irradiation burns the occluding agent into the
      dentinal tubules, thereby resisting the effects of an acidic diet and brushing,
      and increasing the duration of the desensitizing effect.

PMID- 16570566
TI  - Calyceal diverticulum in FDG-PET imaging.
AB  - A 46-year-old female underwent a fluorodeoxyglucose F-18 (FDG) positron emission
      tomography (PET) whole-body scan for tumor screening after showing no symptoms or
      signs. The PET images showed a large FDG-avid lesion in the left renal pelvis,
      with a maximum standard uptake value (SUV) of 10.7 at 1 hour and 3.9 at 3 hours.
      An abdominal computed tomography (CT) scan showed a 3.7-cm cystic lesion with a
      slightly irregular wall in the left kidney. The immediate impression was that of
      a complicated cyst. A histopathologic report after surgery confirmed a calyceal
      diverticulum. To the best of our knowledge, this is the first report of FDG
      uptake in a case of calyceal diverticulum.

PMID- 16570567
TI  - Jejunal tuberculosis: incidental finding on an FDG-PET scan.
AB  - A 32-year-old male had suffered from persistent dull epigastric pain,
      constipation, postprandial vomiting, and body-weight loss for 2 months. An
      abdominal computed tomography (CT) scan showed thickening of the proximal jejunal
      wall. He was also referred to our center for an fluoro-2-deoxy-D-glucose-positron
      emission tomography (FDG-PET) scan because his tumor marker CA19-9 was above 800
      ng/mL and malignancy was suspected. The PET scan showed an FDG-avid lesion over
      the upper left abdomen. Endoscopy of the small intestine revealed focal
      thickening of the mucosal fold and skip ulcer lesions in the jejunum. Culture
      from the biopsy tissue proved the diagnosis of Mycobacterium tuberculosis
      infection. No evidence of pulmonary tuberculosis was detected during further
      evaluation.

PMID- 16570568
TI  - Pneumorrhachis following lumbar puncture: a case report.
AB  - We report a rare case of pneumorrhachis following lumbar puncture. A 4-year-old
      boy was admitted to our hospital with seizures following a head injury and upper
      respiratory infection. Lumbar puncture was performed to rule out central nervous
      system infection. In response to leg pain and weakness a few hours after the
      procedure, lumbar spine computed tomography (CT) revealed pneumorrhachis at the
      level of L5-S1. In a follow-up CT scan 3 days later, the pneumorrhachis resolved
      spontaneously. Pneumorrhachis following diagnostic lumbar puncture is an
      extremely rare condition. We discuss pneumorrhachis and review cases in the
      literature.

PMID- 16570569
TI  - Acute brachial artery thrombosis: a rare complication of diabetic ketoacidosis.
AB  - Diabetes mellitus is a worldwide disease that leads to several acute
      complications including diabetic ketoacidosis, hyperosmolar hyperglycemia, and
      hypoglycemia. In addition, diabetes causes many chronic complications that lead
      to debilitation and diminished quality of life. Diabetic ketoacidosis is one of
      the serious acute complications; however, it is usually preceded by infection,
      acute myocardial infarction, stroke, or other dire events. Rarely does it
      accompany acute arterial thrombosis. Here, we report on a female patient who
      suffered from diabetic ketoacidosis combined with acute brachial artery
      thrombosis. After emergency treatment, including insulin therapy and surgical
      thrombectomy, the brachial artery was rescued and her prognosis was good.

PMID- 16570570
TI  - Developments in the treatment of acute esophageal variceal bleeding.

PMID- 16570571
TI  - Rapid quantitative PCR diagnostic strategy for Charcot-Marie-Tooth 1A and
      hereditary neuropathy with liability to pressure palsies.

PMID- 16570572
TI  - Emergency endoscopic variceal ligation versus somatostatin for acute esophageal
      variceal bleeding.
AB  - BACKGROUND: Endoscopic variceal ligation and somatostatin are widely used for
      treating acute esophageal variceal bleeding. This study compared the efficacy,
      safety, and survival of both therapies. METHODS: Acute esophageal variceal
      bleeding patients were randomized to undergo emergency ligation or receive a
      bolus of 250 microg somatostatin plus infusion at 250 microg/hour for 48 hours
      and undergo ligation subsequently. RESULTS: Three (4.8%) of 62 patients in the
      ligation group and 20 (31.7%) of 63 patients in the somatostatin group
      encountered treatment failure (p = 0.0001). Transfusion requirements were 4.7 +/-
      3.2 units in the ligation group and 6.9 +/- 7.3 units in the somatostatin group
      (p = 0.03). Hospital stay was 7.7 +/- 4.0 days in the ligation group and 10.2 +/-
      9.9 days in the somatostatin group (p = 0.07). Adverse effects occurred in the
      ligation group (20 episodes) and the somatostatin group (27 episodes) (p = 0.2).
      The 42-day mortality rates were 5 patients (8.1%) in the ligation group and 3
      patients (4.8%) in the somatostatin group (p = 0.5). CONCLUSION: Emergency
      ligation was superior to somatostatin in treating acute esophageal variceal
      bleeding, with fewer requirements of transfusion and a tendency toward shorter
      hospital stay. The adverse effects and 42-day mortality rates were similar
      between both treatments.

PMID- 16570573
TI  - Allele-specific all-or-none PCR product diagnostic strategy for Charcot-Marie
      Tooth 1A and hereditary neuropathy with liability to pressure palsies.
AB  - BACKGROUND: We designed allele-specific primers to amplify genomic DNA of
      patients with Charcot-Marie-Tooth 1A (CMT1A) and hereditary neuropathy with
      liability to pressure palsies (HNPP). METHODS: Genomic DNA analysis was performed
      on 40 unrelated CMT1A duplication patients, 25 unrelated HNPP deletion patients,
      and 50 unaffected control individuals. The CMT1A and HNPP patients had previously
      been identified with microsatellite mapping. RESULTS: Amplification products came
      to 3.6 kb in length from the normal proximal CMT1A repeated segment on chromosome
      17p11.2 (proximal CMT1A-REP), 3.57 kb from the normal distal CMT1A repeated
      segment on chromosome 17p11.2 (distal CMT1A-REP), 3.6 kb from HNPP patients, and
      3.58 kb from CMT1A patients. We could identify the mutations by means of agarose
      gel electrophoresis after polymerase chain reaction (PCR) amplification without
      restriction enzyme digestion from 33 of the 40 CMT1A and 19 of the 25 HNPP
      samples. CONCLUSION: Stringently specific primers were used to overcome the
      problem of nonspecific amplification and provide a rapid, all-or-none PCR product
      and efficient screening test for CMT1A and HNPP.

PMID- 16570574
TI  - Expression of c-kit, Flk-1, and Flk-2 receptors in benign and malignant tumors of
      follicular epithelial origin.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a key regulator of
      physiologic as well as pathologic angiogenesis. The response of VEGF to
      endothelial cell mitogenesis and survival, as well as angiogenesis and
      microvascular permeability, is mainly mediated through its receptor-2, VEGFR2
      (kinase domain receptor or fetal liver kinase-1, KDR or Flk-1). This study aimed
      to detect the expression of VEGFR2 in various forms of thyroid tumors. In
      addition, the expression of Flk-2 (receptor for Flt-3) and c-Kit (receptor for
      steel locus factor), which shows strong similarity to Flk-1, was also examined in
      thyroid tumors. METHODS: RT-PCR analyses of c-Kit and immunohistochemical
      staining of c-Kit, Flk-1, and Flk-2 were performed in archived samples of 18
      papillary thyroid carcinoma (PTC), 9 follicular thyroid carcinoma (FTC), 12
      follicular adenoma (FA), and 7 nodular goiter (NG) samples. The data were
      correlated to clinicopathologic features. RESULTS: By RT-PCR analyses, c-Kit
      expression was detected in 22% (4/18) of PTC, 22% (2/9) of FTC, 25% (3/12) of FA,
      and 57% (4/7) of NG samples. However, positive immunostaining signals of c-Kit
      were only observed in 17% (3/18) of PTC samples, and not in the others.
      Similarly, Flk-1 expression was only detected by immunohistochemistry in 67%
      (12/18) of PTC and 43% (3/7) of NG samples, and not in the others. Interestingly,
      the expression of Flk-2 was found in 89% (16/18) of PTC, 89% (8/9) of FTC, 75%
      (9/12) of FA, and 29% (2/7) of NG samples. An inverse relationship of thyroid
      cancer size with Flk-2 expression was found. CONCLUSION: Flk-2 expression was
      detected in various forms of thyroid tumors and increased Flk-2 expression was
      correlated with thyroid tumors with increased transforming activity, suggesting
      that Flk-2 is involved in pathogenic development of thyroid malignancy.
      Similarly, Flk-1 expression was also found in some thyroid tumors, while the
      expression of c-Kit-mediated pathways may not play a major role in thyroid
      tumorigenesis.

PMID- 16570575
TI  - Endovascular treatment of intracranial high-flow arteriovenous fistulas by
      Guglielmi detachable coils.
AB  - BACKGROUND: This study reports our experience in performing transarterial
      Guglielmi detachable coil (GDC) embolization for intracranial high-flow
      arteriovenous fistulas (AVFs) and evaluates its efficacy and safety. METHODS:
      Over 3 years, 13 patients with 14 intracranial high-flow AVFs had been managed by
      transarterial GDC embolization in our institution. There were 6 men and 7 women,
      with a mean age of 27 years. Of these 14 AVFs, 8 were traumatic carotid-cavernous
      fistulas (TCCFs); 5 were AVFs at the frontal, temporal, parieto-occipital lobes,
      or associated with arteriovenous malformation (n = 3); 1 was a tentorium AVF.
      RESULTS: All of these high-flow AVFs were successfully occluded by a single
      session of transarterial GDC embolization. In 8 patients with TCCFs, the nearby
      parent arteries were preserved. The average number of coils was 8 and the average
      length was 126 cm. All AVF-related symptoms resolved immediately or gradually on
      clinical follow-up. No significant procedure-related neurologic complication or
      recurrent AVF was seen. All 13 patients were followed up clinically for an
      average of 16 months (range, 6-25 months). CONCLUSION: Transarterial GDC
      embolization is a useful method in the treatment of intracranial high-flow AVFs.
      GDC affords more control in the placement of coils and proved both efficient and
      safe in the management of intracranial high-flow AVFs.

PMID- 16570576
TI  - Acute hepatitis induced by Chinese hepatoprotective herb, xiao-chai-hu-tang.
AB  - Xiao-chai-hu-tang (syo-saiko-to in Japanese) is a herbal remedy that has been
      widely used in China for treatment of respiratory, hepatobiliary, and
      gastrointestinal diseases, particularly among patients with chronic liver
      disease. However, its safety has recently been challenged. We, herein, report a
      Chinese patient with acute hepatitis induced by this herb. A 52-year-old woman
      presented with weakness, fatigue, and tea-colored urine after continual
      consumption of the decoction of xiao-chai-hu-tang for 1.5 months. Laboratory
      studies disclosed acute hepatitis even though all of the viral hepatitis markers
      were negative. Liver biopsy also revealed a picture of acute hepatocellular
      hepatitis. The symptoms improved after discontinuing the drug, and liver
      biochemical tests normalized 2 months later. The case report reminds us of the
      probable adverse drug reaction of herbs, even in some that are claimed to have
      hepatoprotective effects.

PMID- 16570577
TI  - Bronchogenic cyst in the interatrial septum with a single persistent left
      superior vena cava.
AB  - Bronchogenic cysts are classified as a type of congenital foregut cyst. They are
      usually extrapulmonary and occur mostly along the tracheobronchial tree.
      Intracardiac bronchogenic cysts are very rare. As far as we know, only 3 cases
      have been reported previously. This paper presents a unique case of a 70-year-old
      male who was diagnosed with a bronchogenic cyst in the interatrial septum with a
      concomitant persistent left superior vena cava. He underwent successful complete
      excision of the cyst under cardiopulmonary bypass and enjoyed an uneventful life
      with normal sinus rhythm during the 1-year follow-up. The relevant literature is
      reviewed and an explanation for the embryogenesis of the bronchogenic cyst in
      such a peculiar location is proposed.

PMID- 16570578
TI  - Delayed interval delivery in a triplet pregnancy.
AB  - Due to a surge in the availability of assisted reproductive techniques (ART), the
      incidence of multiple pregnancies is increasing. Preterm labor is a major
      complication in such pregnancies. Preterm delivery of the first fetus is often
      followed by delivery of the remaining fetuses. However, conservative management
      and delayed interval delivery in the remaining fetuses might allow for fetal lung
      maturity and would reduce perinatal morbidities. A 32-year-old female had a
      quadruplet pregnancy after receiving ART. Fetal reduction to triplet pregnancy
      was performed at 11 weeks of gestation. The remaining triplet pregnancy was
      stable until 29 weeks of gestation, when the first triplet was delivered after
      spontaneous rupture of membranes. Under intensive monitoring, the remaining 2
      fetuses were delivered by cesarean section at 31 weeks of gestation. Only the
      first fetus had retinopathy after discharge. In conclusion, delayed interval
      delivery of the remaining fetuses should be attempted after preterm delivery of
      the first fetus.

PMID- 16570579
TI  - Embedded ring injury of the middle finger in an amphetamine abuser.
AB  - Embedded finger-ring injury is not usually encountered in clinical practice, and
      most patients present with psychiatric or physical/mental impairment. We report
      herein an 18-year-old male amphetamine abuser who presented to our emergency
      department (ED) for embedded finger-ring injury over his left middle finger. The
      embedded ring was removed in the ED under heavy sedation, and the wound healed
      uneventfully over 2 weeks. Thereafter, the young man received psychiatric
      treatment. Embedded finger-ring injury has never been reported in a drug abuser
      before.

PMID- 16570580
TI  - [Drugs and preparations for the treatment of burns].
AB  - The paper summarizes drugs and preparations used and developed for the treatment
      of skin burns and presents the modes of defect treatment from the aspect of
      preventing microbial contamination, contact regulation with the external
      environment (breathing, humidity exchange, thermoregulation), healing, and
      formation of a new functional tissue. Its attention is focused on various types
      of substitutes of the damaged or absent skin - autografts, allografts,
      xenografts, and synthetic dressings as well as combined preparations.

PMID- 16570582
TI  - [Preparation of pharmaceuticals in pharmacies. I. Contemporary situation from the
      viewpoint of computer records].
AB  - Pharmaceuticals prepared in pharmacies represent approximately 5 % of the total
      number of dispensed packages, in financial terms approximately 2.3 % of the total
      turnover of a pharmacy. For the preparation of pharmaceuticals, 70 % of
      pharmacies under study use computer files of prescriptions. In most cases, the
      number of recorded prescriptions does not exceed 150, both for preparations made
      in larger amounts and those made individually. But not all prescriptions are
      really used. On the other hand, frequently required prescriptions are often
      missing. Prescriptions used in pharmacies of different regions are similar or
      identical. The computer files of prescriptions could be utilized in a more
      effective way and could also include algorithms to secure the appropriate quality
      of preparation.

PMID- 16570581
TI  - [Natural derivatives of 4H-pyran-4-one].
AB  - The present review paper describes the natural derivatives of 4H-pyran-4-one
      (simple, benzo- and dibenzo-derivatives). It includes their origin, use, and
      particularly in the case of flavonoids their biological actions and therapeutic
      use.

PMID- 16570583
TI  - [Effect of dissolution medium on the release of diltiazem hydrochloride from
      carbomeric matrices].
AB  - The paper focuses on the study of the effect of pH of dissolution medium on the
      release of diltiazem hydrochloride from carbomeric matrices. Swelling of
      carbomers, high-molecular cross-linked anionic polymers, is dependent on the
      value of pH, which decides whether these polymers exist in an ionized or a non
      ionized form. In alkaline medium, carboxylic groups of carbomers ionize and
      hydrate markedly, which also facilitates their interaction with cationic drugs,
      in this case with diltiazem hydrochloride. The development of a sparingly soluble
      complex drug-polymer, the presence of which was demonstrated with the use of
      Fourier IR spectrophotometry, is one of the factors which causes decelerated
      release of the drug as well as decreased swelling of matrices in this dissolution
      medium. In both selected dissolution media, an assumption has been confirmed that
      with an increasing concentration of the polymer in the system a smaller share of
      the drug is released. Drug release from matrix tablets is also influenced by the
      rate of dissolution of the drug in dependence on the pH of the medium. Being a
      salt of a feeble base and a strong acid, diltiazem hydrochloride is more slowly
      soluble in an alkaline medium than in the medium with pH 1.2. This factor also
      contributes to its slower release in the medium of phosphate buffer of pH 7.4.

PMID- 16570584
TI  - [A study of the properties of tablets from mixtures of two size degrees of alpha
      lactose monohydrate and microcrystalline cellulose].
AB  - The paper examines the strength and disintegration time of compacts from the
      mixtures of two types of Tablettosas. Tablettosa 70 and Tablettosa 100 with
      microcrystalline cellulose represented by Vivapur 102. The mixtures of dry
      binders were prepared in the ratios of 3:1, 1:1, and 1:3. The effect of two
      concentrations of the lubricant magnesium stearate on the strength and
      disintegration time of compacts was also examined. Tablet strength increased with
      higher representation of microcrystalline cellulose in the mixture, and decreased
      with higher stearate concentration. The compacts from the mixtures with
      Tablettosa 100 showed higher strength. Disintegration time was highest in the
      compacts with the largest perccintage of microcrystalline cellulose, and longer
      in the case of the mixtures with Tablettosa 100. Stearate did not exert a
      negative effect on disintegration time. In the mixtures of Tablettosas with
      Vivapur 102 in a ratio of 1:1, the effect of the model active ingredient
      acetylsalicylic acid on the above-mentioned properties of tablets was tested.
      acetylsalicylic acid produced a further decrease in the strength of compacts and
      shortened the disintegration time in more instances in the cased of the mixtures
      with Tahlettosa 100.

PMID- 16570585
TI  - [Morin in the therapy of the ischemia-reperfusion damage model of the rat
      kidney].
AB  - The aim of this study was to analyze the protective effects of morin administered
      during the therapy of reperfusion injury of the laboratory rat kidney. Animals
      were randomly divided into five groups (n= 10). One group was left intact. Three
      medicated groups and one placebo group were subjected to ischemia (60 min) and
      reperfusion of the left kidney. Morin was suspended in a 2 ml of 0.5% Avicel
      solution and administered orally by a gastric probe at doses of 5, 10, and 20
      mg.kg(-1) once a day for 15 days. The placebo group was given only 2 ml of 0.5%
      Avicel in the same way. On the 15th day, all the animals were exsanguinated and
      the reperfused kidneys were recovered. Selected biochemical markers in blood were
      assessed: superoxide dismutase, glutathion peroxidase, total antioxidative
      capacity, malondialdehyde, creatinine, urea, and uric acid. Creatinine, urea, and
      total protein were analyzed in urine, and a 24-hour diuresis was recorded. The
      kidney tissue samples were used for histopathological examination. Morin
      supported the organism's own defensive reactions against free radicals and
      decreased lipid peroxidation in the cell membranes and contributed to the
      recovery of kidney functions. The histopathological results confirm 20 mg x kg(
      1) as the most effective dose.

PMID- 16570586
TI  - [Medicinal preparations in the Czech translation of Saliceto's treatise on
      surgery].
AB  - The Latin treatise on surgery by the Italian physician Guglielmo da Saliceto (ca
      1210 to 1276-1280) lists about 300 kinds of medicinal and galenic preparations,
      the most frequently prescribed ones being oils, ointments, and cataplasms. The
      compositions of Saliceto's prescriptions are simplified in comparison with the
      then prescription habits and contain a greater number of chemical active
      ingredients. Preparation of ophthalmic drops by means of distillation or boiling
      on a water bath deserves special attention. The treatise was translated into
      Czech in the first half of the 15th century and provided the basis for Czech
      pharmaceutical terminology.

PMID- 16570587
TI  - How green is ethanol?

PMID- 16570588
TI  - Pretreatment lowers desalination costs.

PMID- 16570589
TI  - OMB proposes to harmonize risk assessments.

PMID- 16570590
TI  - Calculation and uses of mean sediment quality guideline quotients: a critical
      review.
AB  - Fine-grained sediments contaminated with complex mixtures of organic and
      inorganic chemical contaminants can be toxic in laboratory tests and/or cause
      adverse impacts to resident benthic communities. Effects-based, sediment quality
      guidelines (SQGs) have been developed over the past 20 years to aid in the
      interpretation of the relationships between chemical contamination and measures
      of adverse biological effects. Mean sediment quality guideline quotients (mSQGQ)
      can be calculated by dividing the concentrations of chemicals in sediments by
      their respective SQGs and calculating the mean of the quotients for the
      individual chemicals. The resulting index provides a method of accounting for
      both the presence and the concentrations of multiple chemicals in sediments
      relative to their effects-based guidelines. Analyses of considerable amounts of
      data demonstrated that both the incidence and magnitude of toxicity in laboratory
      tests and the incidence of impairment to benthic communities increases
      incrementally with increasing mSQGQs. Such concentration/response relationships
      provide a basis for estimating toxicological risks to sediment-dwelling organisms
      associated with exposure to contaminated sediments with a known degree of
      accuracy. This sediment quality assessment tool has been used in numerous surveys
      and studies since 1994. Nevertheless, mean SQGQs have some important limitations
      and underlying assumptions that should be understood by sediment quality
      assessors. This paper provides an overview of the derivation methods and some of
      the principal advantages, assumptions, and limitations in the use of this
      sediment assessmenttool. Ideally, mean SQGQs should be included with other
      measures including results of toxicity tests and benthic community surveys to
      provide a weight of evidence when assessing the relative quality of contaminated
      sediments.

PMID- 16570591
TI  - Enterococci predictions from partial least squares regression models in
      conjunction with a single-sample standard improve the efficacy of beach
      management advisories.
AB  - Beach health advisories are issued if enterococci (ENT) densities exceed the 30-d
      geometric mean or single-sample water quality criteria. Current ENT enumeration
      procedures require 1 day of incubation; therefore, beach managers make policy
      decisions using 1-day-old data. This is tantamount to using a model that assumes
      ENT density on day t is equal to ENT density on day t-1. Research has shown that
      ENT densities vary over time scales shorterthan a day, calling into question the
      usefulness of the current model for decision-making. We created Dynamic Partial
      Least Square Regression (DPLSR) models for ENT at water quality monitoring
      stations within two adjacent marine recreational sites, Huntington State Beach
      (HSB) and Huntington City (HCB) Beach, California, using publicly available
      environmental data and tested whether these models overcome the drawbacks of the
      current model. The DPLSR models provide a better prediction of ENT than the
      current models based on comparisons of root-mean-square errors of prediction and
      the numbers of type 1 and 2 errors. We compared outcomes in terms of predicted
      illness, swimmers deterred from entering the water, and net benefits to swimmers
      for hypothetical management scenarios where beach advisories were issued based on
      (a) the previously collected sample's ENT density in conjunction with the two
      water quality criteria, and (b) predictions from DPLSR models in conjunction with
      the single-sample standard. At both HSB and HCB the DPLSR scenario produced a
      more favorable balance between illness prevention and recreational access. The
      results call into question the current method of beach management and show that
      model-informed decision-making and elimination of the geometric mean standard
      will aid beach managers in achieving more favorable outcomes in terms of illness
      and access than are presently achieved using 1-day-old measurements, especially
      at beaches where water quality problems are chronic.

PMID- 16570592
TI  - Ethanol's energy return on investment: a survey of the literature 1990-present.
AB  - Various authors have reported conflicting values for the energy return on
      investment (rE) of ethanol manufacture. Energy policy analysts predisposed to or
      against ethanol frequently cite selections from these studies to supporttheir
      positions. This literature review takes an objective look at the disagreement by
      normalizing and comparing the data sets from ten such studies. Six of the
      reviewed studies treat starch ethanol from corn, and four treat cellulosic
      ethanol. Each normalized data set is also submitted to a uniform calculation of
      rEdefined as the total product energy divided by nonrenewable energy input to its
      manufacture. Defined this way rE > 1 indicates that the ethanol product has
      nominally captured at least some renewable energy, and rE > 0.76 indicates that
      it consumes less nonrenewable energy in its manufacture than gasoline. The
      reviewed corn ethanol studies imply 0.84 < or = rE < or = 1.65; three of the
      cellulosic ethanol studies imply 4.40 < or = rE < or = 6.61. The fourth
      cellulosic ethanol study reports rE= 0.69 and may reasonably be considered an
      outlier.

PMID- 16570593
TI  - Absence of mobile carbohydrate domains in dry humic substances proven by NMR, and
      implications for organic-contaminant sorption models.
AB  - The mobility and domain structure of various standard humic substances have been
      investigated by 1H and 1H-13C solid-state nuclear magnetic resonance (NMR)
      experiments. In four dry humic acids, a fulvic acid, a natural organic matter
      sample, and a whole peat sample, segments that undergo fast, large-amplitude
      motions account for <9% of the sample. This disproves a previous suggestion,
      based on 1H NMR data, that flexible domains, presumably carbohydrates, make up
      >40% of various humic acids; these putative mobile domains were also linked to
      dual-mode sorption. In particular, neither the polar alkyl (carbohydrate) nor the
      aromatic components show any fast, large-amplitude mobility. A small fraction of
      mobile nonpolar alkyl segments identified by us before is the only component
      undergoing large-amplitude motions, apart from absorbed water that we observe in
      humic acids exposed to ambient air. 1H-13C wide-line separation NMR shows that,
      contrary to previous suggestions, the dipolar couplings in the aromatic regions
      are smaller than in the polar alkyl segments, most likely due to differences in
      local 1H densities. Series of 1H-13C heteronuclear correlation experiments with
      1H spin diffusion reveal close proximity of aromatic and polar alkyl segments in
      several humic acids, precluding carbohydrate domains on a scale of > 1-nm
      diameter. In the standard peat humic acid, nonpolar aromatic segments also do not
      form sorption domains of significant size, while nonpolar aliphatic domains,
      which we had previously shown to correlate with sorption capacity, have been
      confirmed.

PMID- 16570594
TI  - Perchlorate in pleistocene and holocene groundwater in north-central New Mexico.
AB  - Groundwater from remote parts of the Middle Rio Grande Basin in north-central New
      Mexico has perchlorate (ClO4-) concentrations of 0.12-1.8 micro/L. Because the
      water samples are mostly preanthropogenic in age (0-28000 years) and there are no
      industrial sources in the study area, a natural source of the ClO4- is likely.
      Most of the samples have Br-, Cl-, and SO4(2-) concentrations that are similar to
      those of modern bulk atmospheric deposition with evapotranspiration (ET) factors
      of about 7-40. Most of the ET values for Pleistocene recharge were nearly twice
      that for Holocene recharge. The N03-/Cl- and CIO-/Cl-ratios are more variable
      than those of Br-/Cl- or S04(2-)/Cl-. Samples thought to have recharged under the
      most arid conditions in the Holocene have relatively high N03-/Cl- ratios and low
      delta 15N values (+1 per mil (% per thousand)) similar to those of modern bulk
      atmospheric N deposition. The delta 18O values of the N03- (-4 to 0% per
      thousand) indicate that atmospheric N03- was not transmitted directly to the
      groundwater but may have been cycled in the soils before infiltrating. Samples
      with nearly atmospheric N03-/CI- ratios have relatively high Cl04- concentrations
      (1.0-1.8 ug/L) with a nearly constant Cl04-/CI- mole ratio of (1.4 +/- 0.1) x 10(
      4), which would be consistent with an average Cl04-concentration of 0.093 0.005
      ,ug/L in bulk atmospheric deposition during the late Holocene in north-central
      NM. Samples thought to have recharged under wetter conditions have higher delta
      15N values (+3 to +8 % per thousando), lower NO3-/Cl- ratios, and lower ClO4-/Cl-
      ratios than the ones most likely to preserve an atmospheric signal. Processes in
      the soils that may have depleted atmospherically derived NO3-also may have
      depleted ClO4- to varying degrees prior to recharge. If these interpretations are
      correct, then ClO4- concentrations of atmospheric origin as high as 4 microg/L
      are possible in preanthropogenic groundwater in parts of the Southwest where ET
      approaches a factor of 40. Higher Cl04- concentrations in uncontaminated
      groundwater could occur in recharge beneath arid areas where ET is greater than
      40, where long-term accumulations of atmospheric salts are leached suddenly from
      dry soils, or where other (nonatmospheric) natural sources of ClO4- exist.

PMID- 16570595
TI  - NMR characterization of 13C-benzene sorbed to natural and prepared charcoals.
AB  - We investigated how the NMR properties of uniformly 13C-labeled benzene molecules
      are influenced by sorption to charcoals produced in the laboratory and collected
      from the field following wildfires. Uniformly 13C-labeled benzene was sorbed to
      two charcoals produced in the laboratory at 450 and 850 degrees C. The chemical
      shift of benzene sorbed to the higher-temperature charcoal was 5-6 ppm lower than
      that of benzene sorbed to the lower-temperature charcoal. This difference was
      attributed to stronger diamagnetic ring currents (which cause a shift to lower
      ppm values) in the more condensed or "graphitic" high-temperature charcoal. The
      chemical shift of benzene sorbed to two charcoals collected from the field
      following wildfires indicated a degree of charcoal graphitization intermediate
      between that of the two laboratory-prepared charcoals. Variable contact time and
      dipolar dephasing experiments showed that the molecular mobility of sorbed
      benzene molecules increased with increasing charcoal graphitization, and also
      increased with increasing benzene concentration. We propose that the chemical
      shift displacement of molecules sorbed to charcoal could be used to identify
      molecules sorbed to black carbon in heterogeneous matrixes such as soils and
      sediments, and to establish how condensed or "graphitic" the black carbon is.

PMID- 16570596
TI  - Characteristics of PCDD/F distributions in vapor and solid phases and emissions
      from the Waelz process.
AB  - The Waelz process is a classic method used for recovering zinc from electric arc
      furnace (EAF) dusts containing relatively high concentrations of PCDD/Fs
      (polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans) as well as
      volatile metals, such as Zn, Pb, and Cu, and chlorine. As a result of the
      operating temperature in the cooling process and high carbon and chlorine
      contents, significant PCDD/Fs are formed in the typical Waelz process, causing
      public concerns regarding PCDD/F emissions. In this study, flue gas and ash
      samplings are simultaneously conducted at different sampling points to evaluate
      the removal efficiency and the partitioning of PCDD/Fs between the vapor and
      solid phases in the Waelz plant investigated. With the environment (temperature
      window, sufficient retention time, chlorine, and catalysts available) conducive
      to PCDD/F formation in the dust settling chamber (DSC), a significantly high
      PCDD/F concentration (1223 ng TEQ/Nm3) is measured in flue gas downstream from
      the DSC of the Waelz plant investigated. In addition, the cyclone and bag filter
      adopted in this facility can only remove 51.3% and 69.4%, respectively, of the
      PCDD/Fs in the flue gas, resulting in a high PCDD/F concentration (145 ng
      TEQ/Nm3) measured in the stack gas of the Waelz plant investigated. On the basis
      of treating 1 ton of EAF dust, the total PCDD/F discharge (stack gas emission +
      ash discharge) is 840 ng TEQ/kg EAF dust of the Waelz plant investigated. Because
      of the lack of effective air pollutant control devices for PCDD/Fs, about 560 ng
      TEQ/kg EAF dust are discharged via stack gas in this facility.

PMID- 16570597
TI  - Suppression of dissolved organic carbon by sulfate induced acidification during
      simulated droughts.
AB  - The relationship between dissolved organic carbon (DOC) and the acidification of
      soils and freshwaters by sulfate (SO4(2-)) has been a topic of great debate over
      the last few decades. Most interest has focused on long-term acidification. Few
      have considered the influence of episodic drought-induced acidification in
      peatlands on DOC mobility, even through the increased acidity and ionic strength
      associated with the oxidation of reduced sulfur to SO4(2-) are known to reduce
      DOC solubility. Reduced DOC concentrations during droughts have often been
      attributed to: (i) reduced hydrological export; (ii) physicochemical changes in
      the peat structure; or (iii) changes in the biological production and/or
      consumption of DOC. Our experimental drought simulations on peat cores showed
      that SO4(2-) induced acidification reduced DOC concentrations during droughts.
      However, the relationships between SO4(2-)/pH/ ionic strength and DOC were only
      apparent when the reductions in observed DOC were expressed as a fraction of the
      estimated DOC concentration in the absence of SO4(2-), which were derived from
      soil depth, temperature, and watertable data. This analysis showed that a pH fall
      from 4.3 to 3.5, due to a SO4(2-) rise from < 2.5 to 35 mg L(-1), caused a 60%
      reduction in DOC concentrations. In contrast, poor correlations were recorded
      between S042-/pH/ionic strength and the observed DOC data. As DOC both influences
      acidity and is influenced by acidity, the relative change in DOC needed to be
      considered to disentangle the effect of inputs of mineral acids into a system
      naturally dominated by variable concentrations of organic acids.

PMID- 16570598
TI  - The evaluation of liposome-water partitioning of 8-hydroxyquinolines and their
      copper complexes.
AB  - Bioavailability and toxicity of mixtures are urgent research issues, but usually
      mixtures of exclusively organic chemicals or exclusively metals are investigated.
      In our study, we explored the role of combinations of hydrophobic ionogenic
      organic compounds (HIOCs) with copper (Cu2+)for uptake and bioavailability of
      metals and hydrophobic metal complexes in an in vitro membrane system. We
      investigated the influence of the interactions of copper and 8-hydroxyquinolines,
      both components used in formulations of pesticides, on their partitioning into
      liposomes, which are model systems for biological membranes and are composed of
      lipid bilayers made of phosphatidylcholine. The test set of compounds comprised
      the parent compound 8-hydroxyquinoline and 8-hydroxyquinolines with hydrophobic
      (e.g., 5-chloro-8-hydroxyquinoline, 5,7-dichloro-8-hydroxyquinoline, 5,7-dibromo
      8-hydroxyquinoline) and with hydrophilic (e.g., 8-hydroxyquinoline-5-sulfonic
      acid) substituents. Hydrophobic 8-hydroxyquinolines facilitate the passive uptake
      of copper into phospholipid bilayers by complex formation. Not only the neutral
      species of the ligands and their neutral copper ligand complexes are
      significantly taken up into the membrane, but also the cationic and anionic
      species of the ligands and the cationic complexes. The neutral, anionic, and
      cationic species of 8-hydroxyquinoline and the hydrophobic substituted 8
      hydroxyquinolines exhibit linear correlations between their logarithmic liposome
      water partitioning coefficients (log Klipw) and the logarithmic octanol-water
      partitioning coefficients of their neutral species (log Kow, neutral). The
      neutral species show the strongest partitioning followed by the anionic and
      cationic species. The associated quantitative structure activity relationships
      describing the dependency of log Klipw of the various species from log Kow,
      neutral of the neutral ligand species have slopes between 0.9 and 1. In contrast,
      the partitioning of the neutral and cationic copper-8-hydroxyquinoline complexes
      is dependent on several factors including the hydrophobicity of the ligand, the
      effective molecular size, and the polarization of the complex itself. In
      consequence, there is no linear relationship between log Klipw of these complexes
      and log Kow of the neutral species of their ligands. The complexes with very
      bulky substituents showed a reduced uptake. The Klipw of the nominally neutral
      complexes, where Cu2+ is coordinated with two ligands, were a factor three to
      four higher than the Klipw of the positively charged complexes with only one
      ligand. Although liposome-water partitioning merely describes one element of the
      uptake process into biological membranes, it is a key process for bioavailability
      of hydrophobic compounds and, presumably, also plays a crucial role for
      biological uptake of the described metal organic complexes.

PMID- 16570599
TI  - The effect of aging and pH on Pb(II) sorption processes at the calcite-water
      interface.
AB  - The effect of aging on Pb(II) retention in 1 microM Pb, calcite suspensions at pH
      7.3, 8.2, and 9.4, under room-temperature conditions, was explored via a
      combination of batch sorption-desorption experiments and X-ray absorption
      spectroscopy (XAS). Short-term experiments, up to 12 days, reveal the
      predominance of an adsorption mechanism at pH 8.2, as confirmed by XAS analysis.
      Linear-combination fitting of XANES spectra indicates a dual sorption mechanism,
      with approximately 95% adsorbed and appromicately 5% coprecipitated, and
      approcimately 75% adsorbed and approsimately 25% coprecipitated Pb at pH 7.3 and
      9.4, respectively. For long-term sorption, 60-270 days, slow continuous uptake
      occurs at pH 7.3 and 8.2, determined by EXAFS to be due to an adsorption
      mechanism. At pH 9.4, no further uptake occurs with aging, and the solid-phase
      distribution of Pb is commensurate with that for short-term experiments,
      suggesting that coprecipitated metal may alterthe calcite surface precluding
      further Pb sorption. Desorption experiments indicate that at pH 7.3 and 8.2 long
      term sorption products-constituted primarily of Pb inner-sphere adsorption
      complexes-are reversibly bound. For aged pH 9.4 samples, significant sorption
      irreversibility indicates that the coprecipitated component is not readily
      exchangeable with the aqueous phase, and thus coprecipitation may be effective
      for long-term metal sequestration.

PMID- 16570600
TI  - Effect of ozone on nicotine desorption from model surfaces: evidence for
      heterogeneous chemistry.
AB  - Assessment of secondhand tobacco smoke exposure using nicotine as a tracer or
      biomarker is affected by sorption of the alkaloid to indoor surfaces and by its
      long-term re-emission into the gas phase. However, surface chemical interactions
      of nicotine have not been sufficiently characterized. Here, the reaction of ozone
      with nicotine sorbed to Teflon and cotton surfaces was investigated in an
      environmental chamber by monitoring nicotine desorption over a week following
      equilibration in dry or humid air (approximately 0% or 65-70% RH, respectively).
      The Teflon and cotton surfaces had N2-BET surface areas of 0.19 and 1.17 m2 g(
      1), and water mass uptakes (at 70% RH) of 0 and 7.1% respectively. Compared with
      dry air baseline levels in the absence of O3, gas-phase nicotine concentrations
      decreased by 2 orders of magnitude for Teflon after 50 h at 20-45 ppb O3, and by
      a factor of 10 for cotton after 100 h with 13-15 ppb O3. The ratios of pseudo
      first-order rate constants for surface reaction (r) to long-term desorption (k)
      were r/k = 3.5 and 2.0 for Teflon and cotton surfaces, respectively. These
      results show that surface oxidation was competitive with desorption. Hence,
      oxidative losses could significantly reduce long-term re-emissions of nicotine
      from indoor surfaces. Formaldehyde, N-methylformamide, nicotinaldehyde, and
      cotinine were identified as oxidation products, indicating that the pyrrolidinic
      N was the site of electrophilic attack by O3. The presence of water vapor had no
      effect on the nicotine-O3 reaction on Teflon surfaces. By contrast, nicotine
      desorption from cotton in humid air was unaffected by the presence of ozone.
      These observations are consistent with complete inhibition of ozone-nicotine
      surface reactions in an aqueous surface film present in cotton but not in Teflon
      surfaces.

PMID- 16570601
TI  - Zinc sorption to three gram-negative bacteria: combined titration, modeling, and
      EXAFS study.
AB  - The acid-base and Zn sorption properties of three bacteria, Cupriavidus
      metallidurans CH34, Pseudomonas putida ATCC12633, and Escherichia coli
      K12DH5alpha, were investigated through an original combination of extended X-ray
      absorption fine structure (EXAFS) spectroscopy and equilibrium titration studies.
      Acid-base titration curves of the three strains were fitted with a model
      accounting for three conceptual reactive sites: an acidic (carboxyl and/or
      phosphodiester), a neutral (phosphomonoester), and a basic (amine and/or
      hydroxyl) group. Calculated proton and Zn equilibrium constants and site
      densities compare with literature data. The nature of Zn binding sites was
      studied by EXAFS spectroscopy. Phosphoester, carboxyl, and unexpectedly
      sulfhydryl ligands were identified. Their proportions depended on Zn loading and
      bacterial strain and were consistent with the titration results. These findings
      were compared to the structure and site density of the major cell wall
      components. It appeared that the cumulated theoretical site density of these
      structures (<2 Zn nm(-2)) was much lower than the total site density of the
      investigated strains (16-56 Zn nm(-2)). These results suggest a dominant role of
      extracellular polymeric substances in Zn retention processes, although Zn binding
      to inner cell components cannot be excluded.

PMID- 16570602
TI  - Uptake by cucurbitaceae of soil-Bome contaminants depends upon plant genotype and
      pollutant properties.
AB  - Three Cucurbitaceae, Cucurbita pepo L. subsp. pepo (cv. Black Beauty, true
      zucchini), Cucurbita pepo L. intersubspecific cross (cv. Zephyr, summer squash),
      and Cucumis sativis (cv. Marketmore, cucumber), were grown in rhizotrons
      containing soil contaminated with three classes of highly weathered, hydrophobic
      organic contaminants: (1) technical chlordane, (2) dichlorodiphenylethanes (DDT
      and DDD) and -ethene (DDE), (3) polyaromatic hydrocarbons (PAHs), and heavy metal
      residues. Movement of the contaminants through the soil/plant system was studied
      by comparing contaminant concentration in the bulk soil, the rhizosphere soil
      pore water, the xylem sap, and aerial tissue. This permitted, for the first time,
      calculation of bioconcentration factors (BCFs) based on concentration in the
      xylem sap versus that in the rhizosphere soil pore water. The bioconcentration
      factors so determined for the sum of five chlordane residues (two enantiomers of
      trans-chlordane, TC; two enantiomers of cis-chlordane, CC; and achiral trans
      nonachlor, TN) were 36, 40, and 23 for Black Beauty, Zephyr, and Marketmore,
      respectively. In addition, the xylem sap of each cultivar had a consistent
      enantioselective profile for some of the chiral chlordane components. For the sum
      of dichlorodiphenylethanes and -ethene, comparable BCF values were 19, 4, and
      0.8, respectively. In the case of PAHs, different BCF patterns among the
      cultivars were noted for three- versus four-ring compounds. Similarly, movement
      of heavy metals was cultivar-dependent, with cadmium BCF values 9.5, 3.5, and
      0.6for Black Beauty, Zephyr, and Marketmore, respectively; the analogous BCFs for
      zinc were 9, 11, and 2. Thus, passage from ex planta to in planta regions of the
      soil/plant system is dependent not only on properties of the plant, but also on
      those of the pollutant. Such data will provide insight into transport mechanisms
      of highly hydrophobic organic contaminants, as well as heavy metal contaminants,
      in the soil/plant system.

PMID- 16570603
TI  - Organic material: the primary control on mercury methylation and ambient methyl
      mercury concentrations in estuarine sediments.
AB  - Estuarine environments that have no direct sources of mercury (Hg) pollution may
      have sediment concentrations of methylmercury (MeHg) as high as those of polluted
      marine environments. In this study we examined the biogeochemical factors
      affecting net methylation and sediment MeHg concentrations in an unpolluted
      estuarine environment, the Ore River estuary, which discharges into the Bothnian
      Bay (20-120 ng total Hg g(-1) dry sediment, salinity 3-5% per hundred). We
      analyzed the spatial and temporal differences in surface sediment profiles of
      MeHg concentration, Hg methylation, MeHg demethylation, and concentrations of
      sulfide and oxygen between accumulation and erosion type bottoms. The main
      difference between the bottoms studied was in the proportion of organic material
      (OM) in the sediment, ranging between 0.8% and 10.8%. The pore water sulfide
      concentration profiles also differed considerably between sites and seasons, from
      0 to 20 microM, with 100 microM as the extreme maximum. The sediment MeHg
      concentration profiles (0-10 cm) mostly varied between 0.1 and 7 ng g(-1) dry
      weight (dw, as Hg). The MeHg demethylation rates were relatively low and the
      depth profiles of the rates were relatively constant over season, site, and
      depth. In contrast, both rates and depths of maximum Hg methylation differed
      between the bottoms. The results indicate that the amount of OM accumulated at
      the bottoms was the main factor affecting net MeHg production, while the total
      amount of Hg had little or no influence on the amount of MeHg in the sediment.

PMID- 16570604
TI  - 1,1-dichloroethene as a predominant intermediate of microbial trichloroethene
      reduction.
AB  - A microbial culture derived from a landfill site in Dover, DE consistently
      reduced trichloroethene (TCE) to ethene through 1,1-dichloroethene (DCE) as a
      dominant intermediate in the presence of ampicillin. A constant 1,1-DCE-to-cis
      DCE ratio of 2.4 +/- 0.3 was observed for more than two years, while trans-DCE
      was never detected. Without ampicillin, however, TCE was reduced to ethene almost
      exclusively through cis-DCE, suggesting that the culture contained at leasttwo
      TCE-dechlorinating populations. Two subcultures, which were established using 1,1
      DCE or vinyl chloride as an electron acceptor, exhibited the same 1,1-DCE-to-cis
      DCE ratio when TCE was introduced. PCR amplification of 16S rRNA gene followed by
      sequencing and DGGE analysis indicate that these (sub)cultures contained a
      Dehalococcoides population(s). TCE dechlorination assays with crude cell extract
      showed a DCE distribution pattern similar to that with whole cells. The enzyme
      involved in 1,1-DCE formation was likely a cobalt corrinoid enzyme, as suggested
      by the inhibitory effect of CH3I and photoreversibility of the inhibition. This
      study provides a possible biological mechanism forthe occurrence of 1,1-DCE in
      TCE-contaminated sites.

PMID- 16570605
TI  - Cryptosporidium oocyst surface macromolecules significantly hinder oocyst
      attachment.
AB  - The role Cryptosporidium parvum oocyst surface macromolecules play in controlling
      oocyst adhesion (deposition) kinetics to quartz surfaces has been investigated
      utilizing a radial stagnation point flow system. Deposition kinetics and
      corresponding attachment efficiencies of viable oocysts were compared with those
      after treatment with a digestive enzyme (proteinase K) to cleave these surface
      macromolecules. Low deposition rates were observed with viable oocysts over the
      entire range of ionic strengths (KCl) investigated, even at ionic strengths as
      high as 100 mM where the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of
      colloidal stability predicts the absence of an electrostatic energy barrier.
      "Electrosteric" repulsion between the oocyst surface macromolecules and the
      quartz surface is surmised to cause these low deposition rates and attachment
      efficiencies. However, after removal of these surface macromolecules by the
      digestive enzyme, increased attachment efficiencies were observed over the entire
      range of ionic strengths. This significant increase in the deposition kinetics
      was seen despite the oocysts having a more negative zeta potential following the
      removal of the surface macromolecules. After treatment with proteinase K, the
      oocysts no longer experienced electrosteric repulsive forces, and their
      deposition kinetics followed the general behavior predicted by DLVO theory.

PMID- 16570606
TI  - Chemistry of particle inception and growth during alpha-pinene ozonolysis.
AB  - A flow-tube reactor was used to study the formation of particles from alpha
      pinene ozonation. Particle phase products formed within the first 3-22 s of
      reaction were analyzed online using a scanning mobility particle sizer and two
      particle mass spectrometers. The first, a photoionization aerosol mass
      spectrometer (PIAMS), was used to determine the molecular composition of nascent
      particles between 30 and 50 nm in diameter. The second, a nano-aerosol mass
      spectrometer (NAMS), was used to determine the elemental composition of
      individual particles from 50 nm to below 10 nm in diameter. Molecular composition
      measurements with PIAMS confirm that both the stabilized Criegee intermediate and
      hydroperoxide channels of alpha-pinene ozonolysis are operative. However, these
      channels alone cannot explain the high oxygen content of the particles measured
      with NAMS. The carbon-to-oxygen mole ratios of suspected nucleating agents are in
      the range of 2.25-4.0, while the measured ratios are from 1.9 for 9 nm particles
      to 2.5 and 2.7 for 30 and 50 nm particles, respectively. The large oxygen content
      may arise by cocondensation of small oxygenated molecules such as water or
      multistep reactions with ozone, water, or other species that produce highly
      oxygenated macromolecules. In either case, the increasing ratio with increasing
      particle size suggests that the aerosol becomes less polar with time.

PMID- 16570607
TI  - Calcium-promoted catalytic degradation of PCDDs, PCDFs, and coplanar PCBs under a
      mild wet process.
AB  - The authors achieved highly efficient degradation of polychlorinated aromatic
      compounds, including polychlorinated dibenzo-p-dioxins, dibenzofurans, and dioxin
      like compounds such as coplanar polychlorinated biphenyls (co-PCBs), which are
      known as persistent organic pollutants. Degradation was accomplished in 24 h
      through a simple stirring operation using safe and high workability metallic
      calcium, which acts as both a scavenger and a reducing agent, and Rh/C catalyst
      in an alcohol solution under mild conditions in a sealed tube at 25 degrees C
      without a temperature increase within 0.15 MPa of increasing internal pressure
      during the reaction. In this system, reductive dechlorination by metallic calcium
      and catalytic reduction by Rh/C and generated hydrogen gas, without any external
      addition of hydrogen, exert a synergistic effect on the degradation of
      chlorinated compounds. Alcohol was used as a proton source and hydrogen, which
      was generated by a side reaction, causes an increase in the activity of Rh/C
      catalyst. Through the degradation of 4-chloroanisole in ethyl alcohol, anisole
      and cyclohexyl methyl ether were obtained in good conversions. Using ethyl
      alcohol as a solvent, treatment of dioxins and co-PCBs in a solution was markedly
      effective for degradation to reduce 2806 pg TEQ/ml of initial concentration to
      31.8 pg TEQ/ml; its yield was 98.5%. Moreover, degradation in methyl alcohol took
      place in a 99.3% yield. That concentration ultimately reached 20.3 pg TEQ/ml
      under a mild wet process. All congeners of dioxins and co-PCBs were degraded in
      high conversions. In this degradation, lower aliphatic alcohol, such as methyl
      alcohol, is effective for making a new calcium surface as compared to alcohol
      with more methylene chains. In addition, it seemed that a higher pressure of
      hydrogen was easily generated in methyl alcohol, and then catalytic degradation
      was effectivley influenced.

PMID- 16570608
TI  - Adsorption of polycyclic aromatic hydrocarbons by carbon nanomaterials.
AB  - Carbon nanomaterials are novel manufactured materials, having widespread
      potential applications. Adsorption of hydrophobic organic compounds (HOCs) by
      carbon nanomaterials may enhance their toxicity and affect the fate,
      transformation, and transport of HOCs in the environment. In this research,
      adsorption of naphthalene, phenanthrene, and pyrene onto six carbon
      nanomaterials, including fullerenes, single-walled carbon nanotubes, and
      multiwalled carbon nanotubes was investigated, which is the first systematic
      study on polycyclic aromatic hydrocarbons (PAHs) sorption by various carbon
      nanomaterials. All adsorption isotherms were nonlinear and were fitted well by
      the Polanyi-Manes model (PMM). Through both isotherm modeling and constructing
      "characteristic curve", Polanyi theory was useful to describe the adsorption
      process of PAHs by the carbon nanomaterials. The three fitted parameters (Q0, a,
      and b) of PMM depended on both PAH properties and the nature of carbon
      nanomaterials. For different PAHs, adsorption seems to relate with their
      molecular size, i.e., the larger the molecular size, the lower the adsorbed
      volume capacity (Q0), but higher a and b values. For different carbon
      nanomaterials, adsorption seems to relate with their surface area, micropore
      volume, and the volume ratios of mesopore to micropore. Quantitative
      relationships between these sorbent properties and the estimated parameters of
      PMM were obtained. These relationships may represent a first fundamental step
      toward establishing empirical equations for quantitative prediction of PAH
      adsorption by carbon nanomaterials and possibly other forms of carbonaceous (geo
      ) sorbents, and for evaluating their environmental impact. In addition, high
      adsorption capacity of PAHs by carbon nanotubes may add to their high
      environmental risks once released to the environment, and result in potential
      alteration of PAHs fate and bioavailability in the environment.

PMID- 16570609
TI  - Atmospheric chemistry of N-methyl perfluorobutane sulfonamidoethanol,
      C4F9SO2N(CH3)CH2CH2OH: kinetics and mechanism of reaction with OH.
AB  - Relative rate methods were used to measure the gas-phase reaction of N-methyl
      perfluorobutane sulfonamidoethanol (NMeFBSE) with OH radicals, giving k(OH +
      NMeFBSE) = (5.8 +/- 0.8) x 10(-12) cm3 molecule(-1) s(-1) in 750 Torr of air
      diluent at 296 K. The atmospheric lifetime of NMeFBSE is determined by reaction
      with OH radicals and is approximately 2 days. Degradation products were
      identified by in situ FTIR spectroscopy and offline GC-MS and LC-MS/MS analysis.
      The primary carbonyl product C4F9SO2N(CH3)CH2CHO, N-methyl perfluorobutane
      sulfonamide (C4F9SO2NH(CH3)), perfluorobutanoic acid (C3F7C(O)OH),
      perfluoropropanoic acid (C2F5C(O)OH), trifluoroacetic acid (CF3C(O)OH), carbonyl
      fluoride (COF2), and perfluorobutane sulfonic acid (C4F9SO3H) were identified as
      products. A mechanism involving the addition of OH to the sulfone double bond was
      proposed to explain the production of perfluorobutane sulfonic acid and
      perfluorinated carboxylic acids in yields of 1 and 10%, respectively. The gas
      phase N-dealkylation product, N-methyl perfluorobutane sulfonamide (NMeFBSA), has
      an atmospheric lifetime (>20 days) which is much longer than that of the parent
      compound, NMeFBSE. Accordingly,the production of NMeFBSA exposes a mechanism by
      which NMeFBSE may contribute to the burden of perfluorinated contamination in
      remote locations despite its relatively short atmospheric lifetime. Using the
      atmospheric fate of NMeFBSE as a guide, it appears that anthropogenic production
      of N-methyl perfluorooctane sulfonamidoethanol (NMeFOSE) contributes to the
      ubiquity of perfluoroalkyl sulfonate and carboxylate compounds in the
      environment.

PMID- 16570610
TI  - Secondary organic aerosol formation from isoprene photooxidation.
AB  - Recent work has shown that the atmospheric oxidation of isoprene (2-methyl-1,3
      butadiene, C5H8) leads to the formation of secondary organic aerosol (SOA). In
      this study, the mechanism of SOA formation by isoprene photooxidation is
      comprehensively investigated, by measurements of SOA yields over a range of
      experimental conditions, namely isoprene and NOx concentrations. Hydrogen
      peroxide is used as the radical precursor, substantially constraining the
      observed gas-phase chemistry; all oxidation is dominated by the OH radical, and
      organic peroxy radicals (RO2) react only with HO2 (formed in the OH + H2O2
      reaction) or NO concentrations, including NOx-free conditions. At high NOx,
      yields are found to decrease substantially with increasing [NOx], indicating the
      importance of RO2 chemistry in SOA formation. Under low-NOx conditions, SOA mass
      is observed to decay rapidly, a result of chemical reactions of semivolatile SOA
      components, most likely organic hydroperoxides.

PMID- 16570611
TI  - Modulation of the cytotoxicity and genotoxicity of the drinking water
      disinfection byproduct lodoacetic acid by suppressors of oxidative stress.
AB  - Drinking water disinfection byproducts (DBPs) are generated by the chemical
      disinfection of water and may pose a hazard to the public health. Previously we
      demonstrated that iodoacetic acid was the most cytotoxic and genotoxic DBP
      analyzed in a mammalian cell system. Little is known of the mechanisms of its
      genotoxicity. The involvement of oxidative stress in the toxicity of iodoacetic
      acid was analyzed with the antioxidants catalase and butylated hydroxyanisole
      (BHA). lodoacetic acid toxicity was quantitatively measured with and without
      antioxidants in Salmonella typhimurium strain TA100 and with Chinese hamster
      ovary (CHO) cells. The endpoints included cytotoxicity in S. typhimurium or in
      CHO cells, mutagenicity in S. typhimurium, and genotoxicity in CHO cells. Neither
      catalase nor BHA reduced the level of iodoacetic acid induced cytotoxicity in S.
      typhimurium. In CHO cells neither antioxidant caused a significant reduction in
      iodoacetic acid induced cytotoxicity. However, in S. typhimurium, BHA or catalase
      reduced the mutagenicity of iodoacetic acid by 33.5 and 26.8%, respectively.
      Likewise, BHA or catalase reduced iodoacetic acid induced genomic DNA damage by
      86.5 and 42%, respectively. These results support the hypothesis that oxidative
      stress is involved in the induction of genotoxicity and mutagenicity by
      iodoacetic acid.

PMID- 16570612
TI  - Interactions between microbial iron reduction and metal geochemistry: effect of
      redox cycling on transition metal speciation in iron bearing sediments.
AB  - Microbial iron reduction is an important biogeochemical process that can affect
      metal geochemistry in sediments through direct and indirect mechanisms. With
      respectto Fe(III) (hydr)oxides bearing sorbed divalent metals, recent reports
      have indicated that (1) microbial reduction of goethite/ferrihydrite mixtures
      preferentially removes ferrihydrite, (2) this process can incorporate previously
      sorbed Zn(II) into an authigenic crystalline phase that is insoluble in 0.5 M
      HCl, (3) this new phase is probably goethite, and (4) the presence of
      nonreducible minerals can inhibit this transformation. This study demonstrates
      that a range of sorbed transition metals can be selectively sequestered into a
      0.5 M HCl insoluble phase and that the process can be stimulated through
      sequential steps of microbial iron reduction and air oxidation. Microbial
      reduction experiments with divalent Cd, Co, Mn, Ni, Pb, and Zn indicate that all
      metals save Mn experienced some sequestration, with the degree of metal
      incorporation into the 0.5 M HCl insoluble phase correlating positively with
      crystalline ionic radius at coordination number = 6. Redox cycling experiments
      with Zn adsorbed to synthetic goethite/ferrihydrite or iron-bearing natural
      sediments indicate that redox cycling from iron reducing to iron oxidizing
      conditions sequesters more Zn within authigenic minerals than microbial iron
      reduction alone. In addition, the process is more effective in
      goethite/ferrihydrite mixtures than in iron-bearing natural sediments. Microbial
      reduction alone resulted in a -3x increase in 0.5 M HCl insoluble Zn and
      increased aqueous Zn (Zn-aq) in goethite/ferrihydrite, but did not significantly
      affect Zn speciation in natural sediments. Redox cycling enhanced the Zn
      sequestration by approximately 12% in both goethite/ferrihydrite and natural
      sediments and reduced Zn-aq to levels equal to the uninoculated control in
      goethite/ferrihydrite and less than the uninoculated control in natural
      sediments. These data suggest that in situ redox cycling may serve as an
      effective method for

PMID- 16570614
TI  - Thermodynamic stability relations in redox systems.
AB  - Graphical stability relations in redox systems known as Pourbaix diagrams are
      analyzed employing the concept of overall stability of chemical species in
      multiple chemical reaction systems recently developed by us (Fishtik, I. J. Phys.
      Chem. B 2005, 109, 3851). The overall stability approach provides a simple and
      systematic algorithm for generating thermodynamically and stoichiometrically
      consistent Pourbaix diagrams that are referred to as overall Pourbaix diagrams.
      The conditions under which the conventional Pourbaix diagrams coincide with the
      overall Pourbaix diagrams are also discussed.

PMID- 16570615
TI  - Monitoring the soot emissions of passing cars.
AB  - We report on the first application of a novel fast on-road sensing method for
      measurement of particulate emissions of individual passing passenger cars. The
      studywas motivated by the shift of interest from gases to particles in connection
      with strong adverse health effects. The results correspond very much to findings
      by Beaton et al. (Science, May 19,1995) for gaseous hydrocarbon and CO emissions:
      A small percentage of "superpolluters" (here 5%) account for a high percentage
      (here 43%) of the pollution (here elemental carbon). We estimate that up to 50%
      of the particulate emissions of vehicles could be avoided on the basis of the
      present legislation, if on-road monitoring would be applied to enforce
      maintenance. Our fast sensing method for particles is based on photoelectron
      emission from the emitted airborne soot particles in combination with a CO2
      sensor delivering a reference.

PMID- 16570613
TI  - Use of synthetic data to evaluate positive matrix factorization as a source
      apportionment tool for PM2.5 exposure data.
AB  - Positive matrix factorization (PMF) was applied to synthetic datasets that
      simulate personal exposures to airborne PM2.5 from 12 sources. Three
      differentfilter analysis scenarios using different analytical chemistry
      techniques were considered. The full suite scenario quantified elemental carbon,
      organic carbon, inorganic ions, trace elements, and trace organic species
      including carboxylic acids and organic compounds with -OH functionality. A second
      scenario excluded trace elements and a third assumed that derivatization steps to
      quantify polar organic compounds were not performed. Similar errors in source
      apportionment were seen with all three scenarios. In most cases, PMF failed to
      separate out factors corresponding to road dust and vegetative debris, two
      sources that made relatively uniform contributions to the synthetic exposures.
      Factors representing wood smoke, natural gas combustion, and meat cooking sources
      were difficult to identify due to a lack of unique tracers with concentrations
      reliably above the detection limits assumed in the study. Factors representing
      cigarette smoke, candle smoke, gasoline exhaust, and secondary aerosols were
      comparatively easy to identify. When contributions from a pair of sources, such
      as diesel and gasoline exhaust, were highly correlated in the synthetic datasets,
      a single factor corresponding to both sources was usually found.

PMID- 16570616
TI  - Compound-specific isotope analysis coupled with multivariate statistics to source
      apportion hydrocarbon mixtures.
AB  - Compound Specific Isotope Analysis (CSIA) has been shown to be a useful tool for
      assessing biodegradation, volatilization, and hydrocarbon degradation. One major
      advantage of this technique is that it does not rely on determining absolute or
      relative abundances of individual components of a hydrocarbon mixture which may
      change considerably during weathering processes. However, attempts to use
      isotopic values for linking sources to spilled or otherwise unknown hydrocarbons
      have been hampered by the lack of a robust and rigorous statistical method for
      testing the hypothesis that two samples are or are not the same. Univariate tests
      are prone to Type I and Type II error, and current means of correcting error make
      hypothesis testing of CSIA source-apportionment data problematic. Multivariate
      statistical tests are more appropriate for use in CSIA data. However, many
      multivariate statistical tests require high numbers of replicate measurements.
      Due to the high precision of IRMS instruments and the high cost of CSIA analysis,
      it is impractical, and often unnecessary, to perform many replicate analyses. In
      this paper, a method is presented whereby triplicate CSIA information can be
      projected in a simplified data-space, enabling multivariate analysis of variance
      (MANOVA) and highly precise testing of hypotheses between unknowns and putative
      sources. The method relies on performing pairwise principal components analysis
      (PCA),then performing a MANOVA upon the principal component variables (for
      instance, three, using triplicate analyses) which capture most of the variability
      in the original data set. A probability value is obtained allowing the
      investigator to state whether there is a statistical difference between two
      individual samples. A protocol is also presented whereby results of the coupled
      pairwise PCA-MANOVA analysis are used to down-select putative sources for other
      analysis of variance methods (i.e., PCA on a subset of the original data) and
      hierarchical clustering to look for relationships among samples which are not
      significantly different. A Monte Carlo simulation of a 10 variable data set;
      tanks used to store, distribute, and offload fuels from Navy vessels; and a
      series of spilled oil samples and local tug boats from Norfolk, VA (U.S.A.) were
      subjected to CSIA and the statistical analyses described in this manuscript, and
      the results are presented. The analysis techniques described herein combined with
      traditional forensic analyses provide a collection of tools suitable for source
      apportionment of hydrocarbons and any organic compound amenable to GC-combustion
      IRMS.

PMID- 16570617
TI  - Measuring the trace elemental composition of size-resolved airborne particles.
AB  - A new method to measure the trace elemental composition of size-resolved airborne
      particles that uses acetone extraction followed by ICPMS analysis is compared to
      three other established methods: copper anode XRF, molybdenum anode XRF, and an
      ICPMS method that uses HF digestion. The method detection limit (MDL), accuracy,
      and precision of each method is studied through the analysis of ambient samples
      collected in California. The MDLs of the new acetone-ICPMS method are similar to
      MDLs for the established HF-ICPMS method. Both sets of ICPMS MDLs are 1-3 orders
      of magnitude lower than XRF MDLs for approximately 50 elements other than the
      light crustal elements such as silicon, sulfur, calcium, and zinc. The accuracy
      of the acetone-ICPMS method was verified by comparison to measurements made using
      ion chromatography and the HF-ICPMS method. The acetone-ICPMS analysis method was
      more precise than the conventional HF-ICPMS method for collocated measurements.
      Both ICPMS methods were more precise than XRF for most elements. The size
      distribution of 21 elements contained in ambient particles collected with cascade
      impactors could be measured with good precision using the new acetone-ICPMS
      analysis method: lithium, sulfur, potassium, titanium, vanadium, manganese, iron,
      gallium, germanium, arsenic, selenium, bromine, rubidium, strontium, cadmium,
      tin, antimony, barium, thallium, lead, and bismuth. It is likely that the size
      distribution of an additional 9 elements could also be measured when
      concentrations are sufficiently high: phosphorus, molybdenum, niobium, palladium,
      cesium, europium, holmium, platinum, and uranium. None of the conventional
      methods were able to measure the size distribution of these elements with
      acceptable precision under the conditions studied. The new acetone-ICPMS method
      should provide useful data for the study of the health effects of airborne
      particles.

PMID- 16570618
TI  - Comparison of analytical techniques for dynamic trace metal speciation in natural
      freshwaters.
AB  - Several techniques for speciation analysis of Cu, Zn, Cd, Pb, and Ni are used in
      freshwater systems and compared with respect to their performance and to the
      metal species detected. The analytical techniques comprise the following: (i)
      diffusion gradients in thin-film gels (DGT); (ii) gel integrated microelectrodes
      combined to voltammetric in situ profiling system (GIME-VIP); (iii) stripping
      chronopotentiometry (SCP); (iv) flow-through and hollow fiber permeation liquid
      membranes (FTPLM and HFPLM); (v) Donnan membrane technique (DMT); (vi)
      competitive ligand-exchange/stripping voltammetry (CLE-SV). All methods could be
      used both under hardwater and under softwater conditions, although in some cases
      problems with detection limits were encountered at the low total concentrations.
      The detected Cu, Cd, and Pb concentrations decreased in the order DGT > or = GIME
      VIP > or = FTPLM > or = HFPLM approximately = DMT (>CLE-SV for Cd), detected Zn
      decreased as DGT > or = GIME-VIP and Ni as DGT > DMT, in agreement with the known
      dynamic features of these techniques. Techniques involving in situ measurements
      (GIME-VIP) or in situ exposure (DGT, DMT, and HFPLM) appear to be appropriate in
      avoiding artifacts which may occur during sampling and sample handling.

PMID- 16570619
TI  - Model predictions of metal speciation in freshwaters compared to measurements by
      in situ techniques.
AB  - Measurements of trace metal species in situ in a softwater river, a hardwater
      lake, and a hardwater stream were compared to the equilibrium distribution of
      species calculated using two models, WHAM 6, incorporating humic ion binding
      model VI and visual MINTEQ incorporating NICA-Donnan. Diffusive gradients in thin
      films (DGT) and voltammetry at a gel integrated microelectrode (GIME) were used
      to estimate dynamic species that are both labile and mobile. The Donnan membrane
      technique (DMT) and hollow fiber permeation liquid membrane (HFPLM) were used to
      measure free ion activities. Predictions of dominant metal species using the two
      models agreed reasonably well, even when colloidal oxide components were
      considered. Concentrations derived using GIME were generally lower than those
      from DGT, consistent with calculations of the lability criteria that take into
      account the smaller time window available forthe fluxto GIME. Model predictions
      of free ion activities generally did not agree with measurements, highlighting
      the need for further work and difficulties in obtaining appropriate input data.

PMID- 16570620
TI  - Open-system chamber for measurements of gas exchanges at plant level.
AB  - Gas exchanges of whole canopy can be studied by covering entire plants with a
      chamber and using portable infrared gas analyzers (IRGAs) to measure CO2 and H2O
      exchanged with the air blown through the chamber enclosure. The control of
      temperature rise inside the chamber, which should be kept low, and the accurate
      measurement of the air flow are two crucial aspects for realistic and precise
      estimation of photosynthesis and transpiration. An automated open-system plant
      chamber (clear flexible balloon enclosure) for small plants was developed to
      ameliorate such a technique. The temperature rise is here predicted by heat
      balance analysis inside the chamber. The analysis shows that when as much as 500
      W m2 of solar radiation is converted to sensible heat, a flow rate of 0.98 mol s(
      1) (approximately = 20 L s(-1)) of air blown into a cylinder-shaped enclosure
      (0.8 m high, 0.5 m wide) is adequate to limit temperature increase to 2 K. An
      improved calibration for the measurement of the chamber airflow was obtained by
      combining the use of a Pitot tube anemometer with the classical CO2 injection
      approach. The concentration increase due to the injection of CO2 at a known rate
      into the chamber was predicted by the air flow calculated from the "Pitot" air
      velocity. The turbulent regime of air assured that a single-point Pitot
      measurement was enough for a good estimation (slope = 0.99; R2 = 0.999) of the
      actual air flow. The open-system chamber was tested on potted sunflower
      (Helianthus annuus, L.) and maize (Zea mays, L.) plants under variable solar
      radiation, temperature, and air humidity during the daytime. As expected, similar
      rates of maximal leaf-area based photosynthesis (about 40 micromol m(-2) s(-1))
      were observed in the two species confirming the reliability of our system. The
      consistency of data also resulted from the typical relationships observed between
      photosynthetic rate and light.

PMID- 16570621
TI  - Uptake of iron cyanide complexes into willow trees.
AB  - The uptake of iron cyanide into willows was studied. Trees were grown in
      solutions with Prussian blue, ferricyanide, or ferrocyanide. Iron cyanide
      speciation in solution was determined by HPLC during the experiment. Total
      cyanide and total iron in solution and trees were measured at the end of the
      experiments. Ferrocyanide wasthe dominating species in most solutions at the end.
      Ferricyanide was preferably taken up from solutions. Between 20 and 83% of the
      cyanide was lost from the solutions, and up to 28% could be recovered from the
      plants, mainly from roots. Cyanide could also be detected in stems and leaves of
      most exposed trees. Uptake was increased when no other nitrogen source but
      cyanide was present in solutions. Iron contents in exposed trees, compared to
      controls, increased significantly. The ratio of iron to cyanide remained rather
      stable in solution, but changed to higher values inside the plants. This
      indicates that iron and cyanide were taken up together as a complex, which was
      dissolved inside plants, and then cyanide was metabolized. No toxic effects could
      be seen. The study shows that trees can take up and metabolize iron cyanide
      complexes, making phytoremediation of iron cyanide waste a feasible option.

PMID- 16570623
TI  - Oxidation of antibacterial molecules by aqueous ozone: moiety-specific reaction
      kinetics and application to ozone-based wastewater treatment.
AB  - Ozone and hydroxyl radical (*OH) reaction kinetics were measured for 14
      antibacterial compounds from nine structural families, to determine whether
      municipal wastewater ozonation is likely to result in selective oxidation of
      these compounds' biochemically essential moieties. Each substrate is oxidized by
      ozone with an apparent second-order rate constant, k''(O3,app) > 1 x 10(3) M(-1)
      s(-1), at pH 7, with the exception of N(4)-acetylsulfamethoxazole (K''(O3,app) is
      2.5 x 102 M(-1) s(-1)). k''(O3,app) values (pH 7) for macrolides,
      sulfamethoxazole, trimethoprim, tetracycline, vancomycin, and amikacin appear to
      correspond directly to oxidation of biochemically essential moieties. Initial
      reactions of ozone with N(4)-acetylsulfamethoxazole, fluoroquinolones,
      lincomycin, and beta-lactams do not lead to appreciable oxidation of
      biochemically essential moieties. However, ozone oxidizes these moieties within
      fluoroquinolones and lincomycin via slower reactions. Measured k''(O3,app) values
      and second-order *OH rate constants, k''(*OH,app) were utilized to characterize
      pollutant losses during ozonation of secondary municipal wastewater effluent.
      These losses were dependent on k''(O3,app), but independent of k''(*OH,app).
      Ozone doses > or =3 mg/L yielded > or =99% depletion of fast-reacting substrates
      (K''(O3,app) > 5 x 10(4) M(-1) s(-1)) at pH 7.7. Ten substrates reacted
      predominantly with ozone; only four were oxidized predominantly by .OH. These
      results indicate that many antibacterial compounds will be oxidized in wastewater
      via moiety-specific reactions with ozone.

PMID- 16570622
TI  - Seasonal changes of metals in willow (Salix sp.) stands for phytoremediation on
      dredged sediment.
AB  - Fast growing biomass plants such as Salix species are promising for use in
      phytoremediation of contaminated land. This study assessed the seasonal
      variations and changes with stand age in metal concentrations of S. fragilis L.
      and S. triandra L. grown in field conditions on contaminated dredged sediment
      substrates with comparable properties. A lesser proportion of total soil Cd was
      extractable by ammonium-acetate in the 6-year-old stand (6%) compared to the 1
      year-old stand (17%). This suggests that the potential to remove metals from the
      site declines with tree age. Metal concentrations in willow biomass compartments
      decreased with stand age. Concentrations of Cd and Zn in leaves, wood, and bark
      increased toward the end of the growing season, irrespective of the species. Only
      Cd behavior offered limited prospects for targeting effective removal of the
      metal from the sediment through repeated harvest. The most efficient removal of
      Cd would require the combined harvest of stems and leaves; at the same time the
      risk of spreading Cd and Zn to the surroundings with leaf fall would be avoided.

PMID- 16570624
TI  - Evaluation of mesoporous cyclodextrin-silica nanocomposites for the removal of
      pesticides from aqueous media.
AB  - The treatment of aqueous solutions containing various pesticides by cyclodextrin
      functionalized mesoporous silica adsorbents was investigated. The pesticides
      studied belonged to three chemical structure classes: hexachlorocyclohexane
      based, hexachlorobicycloheptene-based, and p,p' substituted biphenyl-based
      pesticides. The solutions studied contained a mass concentration with respect to
      each pesticide in the range of 0.060-0.270 microg/mL, values that are
      consistentwith the low levels typically encountered in environmental samples.
      Adsorbents containing low to intermediate amounts of cyclodextrin groups were
      found to have optimal adsorption affinity toward the pesticides. The materials
      were particularly specific toward p,p'substituted diphenyl-based pesticides such
      as DDT and DDE.

PMID- 16570625
TI  - Chemical stability of acid rock drainage treatment sludge and implications for
      sludge management.
AB  - To assess the chemical stability of sludges generated by neutralizing acid rock
      drainage (ARD) with alkaline reagents, synthetic ARD was treated with hydrated
      lime (batch and high-density sludge process), limestone, and two proprietary
      reagents (KB-1 and Bauxsol). The amorphous metal hydroxide sludge produced was
      leached using deionized water, U.S. EPA methods (toxicity characteristic leaching
      procedure, synthetic precipitation leaching procedure), and the new strong acid
      leach test (SALT), which leaches the sludge with a series of sulfuric acid
      extractant solutions; the pH decreases by approximately 1 pH unit with each test,
      until the final pH is approximately 2. Sludges precipitated by all reagents had
      very similar leachabilities except for KB-1 and Bauxsol, which released more
      aluminum. SALT showed that lowering the pH of the leaching solution mobilized
      more metals from the sludges. Iron, aluminum, copper, and zinc began to leach at
      pH 2.5-3, approximately 4.5, approximately 5.5, and 6-6.5, respectively. The
      leachability of ARD treatment sludges is determined by the final pH of the
      leachate. A higher neutralization potential (e.g., a greater content of unreacted
      neutralizing agent) makes sludges inherently more chemically stable. Thus, when
      ARD or any acidic metalliferous wastewater is treated, a choice must be made
      between efficient reagent use and resistance to acid attack.

PMID- 16570626
TI  - Spectroscopic study of the impact of arsenic speciation on arsenic/phosphorus
      uptake and plant growth in tumbleweed (Salsola kali).
AB  - This manuscript reports the toxic effects of As2O3 (arsenic trioxide) and As2O5
      (arsenic pentoxide) on S. kali as well as the arsenic and phosphate uptake and
      arsenic coordination within plant tissues. Plants were germinated and grown for
      15 days on a Hoagland-modified medium containing either As(III) (arsenic
      trioxide) or As(V) (arsenic pentoxide). Subsequently, the seedlings were measured
      and analyzed using inductively coupled plasma optical emission spectroscopy and X
      ray absorption spectroscopy techniques. Plants stressed with 2 mg L(-1) of
      whichever As(III) or As(V) concentrated 245 +/- 19, 30 +/- 1, and 60 +/- 3 mg As
      kg(-1) dry weight or 70 +/- 6, 10 +/- 0.3, and 27 +/- 3 mg As kg(-1) dry weight
      in roots, stems, and leaves, respectively. Arsenate was less toxic, and more As
      translocation occurred from the roots to the leaves. All treatments reduced P
      concentration at root level; however, only As(V) at 2 and 4 mg L(-1) reduced P
      concentration at leaf level. Regardless the arsenic species supplied to the
      plants, arsenic was found in plant tissues as As(III) coordinated to three sulfur
      ligands with an interatomic distance of approximately 2.25 angstroms.

PMID- 16570627
TI  - Bioremediation of groundwater contaminated with gasoline hydrocarbons and
      oxygenates using a membrane-based reactor.
AB  - The objective of this study was to operate a novel, field-scale, aerobic
      bioreactor and assess its performance in the ex situ treatment of groundwater
      contaminated with gasoline from a leaking underground storage tank in Pascoag,
      RI. The groundwater contained elevated concentrations of MTBE (methyl tert-butyl
      ether), TBA (tert-butyl alcohol), TBF (tert-butyl formate), BTEX (benzene,
      toluene, ethyl benzene, and xylene isomers), and other gasoline additives (tert
      amyl methyl ether, di-isopropyl ether, tert-amyl alcohol, methanol, and acetone).
      The bioreactor was a gravity-flow membrane-based system called a Biomass
      Concentrator Reactor (BCR) designed to retain all biomass within the reactor. It
      was operated for six months at an influent flow rate that ultimately reached 5
      gpm. The goal was to achieve a removal of all contaminants to <5 microg/L, which
      is the California Drinking Water advisory for MTBE. The concentration of TBA, an
      MTBE biodegradation byproduct, was consistently lower than that of MTBE. The
      other daughter compound detected in the influent, TBF, was degraded to
      concentrations below the detection limit of 0.02 microg/L. BTEX were consistently
      degraded to significantly lower levels in the effluent throughout the duration of
      the study (<1 microg/L). A similar high removal efficiency of the other gasoline
      oxygenates present in the groundwater (TAME, DIPE, and TAA) was also achieved.
      Dissolved organic carbon analysis demonstrated the ability of the bioreactor to
      produce high quality effluents with nonpurgeable organic carbon (NPOC) averaging
      approximately 50% lowerthan the NPOC concentrations in the influent contaminated
      groundwater.

PMID- 16570628
TI  - Assessing degradation rates of chlorinated ethylenes in column experiments with
      commercial iron materials used in permeable reactive barriers.
AB  - Multiple column experiments were performed using two commercial iron materials to
      evaluate the necessity and usefulness of preliminary investigations in permeable
      reactive barrier (PRB) design for chlorinated organics. Experiments were
      performed with contaminated groundwater and involved fresh iron granules or
      altered iron material excavated from PRBs. The determination of first-order rate
      coefficients by global nonlinear least-squares fittings indicated a variability
      in rate coefficients on 1 or 2 orders of magnitude. Geometric mean values of
      surface area normalized rate coefficients (in 10(-5) L m(-2) h(-1)) for fresh
      gray cast iron and iron sponge, respectively, are: tetrachloroethene (4.5, 2.6),
      trichloroethene (8.1, 3.3), cis-1,2-dichloroethene (3.1, 2.9), trans-1,2
      dichloroethene (9.5, 5.3), 1,1-dichloroethene (4.0, 4.4), and vinyl chloride
      (1.6, 6.1). The increasing rate coefficients with decreasing grade of
      chlorination, which characterize degradation at iron sponge are linearly related
      to diffusion coefficients in water, suggesting diffusion limitation in the
      degradation process for this particular material, possibly due to a high inner
      surface. The variability in rate coefficients seems to be too high to use mean
      rate coefficients from published studies in the design procedure of PRBs, and
      variabilities cannot be related to groundwater characteristics, waterflow through
      the reactive cells, or secondary corrosion reactions.

PMID- 16570629
TI  - Fertilization stimulates anaerobic fuel degradation of antarctic soils by
      denitrifying microorganisms.
AB  - Human activities in the Antarctic have resulted in hydrocarbon contamination of
      these fragile polar soils. Bioremediation is one of the options for remediation
      of these sites. However, little is known about anaerobic hydrocarbon degradation
      in polar soils and the influence of bioremediation practices on these processes.
      Using a field trial at Old Casey Station, Antarctica, we assessed the influence
      of fertilization on the anaerobic degradation of a 20-year old fuel spill.
      Fertilization increased hydrocarbon degradation in both anaerobic and aerobic
      soils when compared to controls, but was of most benefit for anaerobic soils
      where evaporation was negligible. This increased biodegradation in the anaerobic
      soils corresponded with a shift in the denitrifier community composition and an
      increased abundance of denitrifiers and benzoyl-CoA reductase. A microcosm study
      using toluene and hexadecane confirmed the degradative capacity within these
      soils under anaerobic conditions. It was observed that fertilized anaerobic soil
      degraded more of this hydrocarbon spike when incubated anaerobically than when
      incubated aerobically. We conclude that denitrifiers are actively involved in
      hydrocarbon degradation in Antarctic soils and that fertilization is an effective
      means of stimulating their activity. Further, when communities stimulated to
      degrade hydrocarbons under anaerobic conditions are exposed to oxygen,
      hydrocarbon degradation is suppressed. The commonly accepted belief that
      remediation of polar soils requires aeration needs to be reevaluated in light of
      this new data.

PMID- 16570630
TI  - Early breakthrough of molybdenum and uranium in a permeable reactive barrier.
AB  - A permeable reactive barrier (PRB) using zerovalent iron (ZVI) was installed at a
      site near Canon City, CO, to treat molybdenum (Mo) and uranium (U) in
      groundwater. The PRB initially decreased Mo concentrations from about 4.8 to less
      than 0.1 mg/L; however, Mo concentrations in the ZVI increased to 2.0 mg/L after
      about 250 days and continued to increase until concentrations in the ZVI were
      about 4 times higherthan in the influent groundwater. Concentrations of U were
      reduced from 1.0 to less than 0.02 mg/L during the same period. Investigations of
      solid-phase samples indicate that (1) calcium carbonate, iron oxide, and sulfide
      minerals had precipitated in pores of the ZVI; (2) U and Mo were concentrated in
      the upgradient 5.1 cm of the ZVI; and (3) calcium was present throughout the ZVI
      accounting for up to 20.5% of the initial porosity. Results of a column test
      indicated that the ZVI from the PRB was still reactive for removing Mo and that
      removal rates were dependenton residence time and pH. The chemical evolution of
      the PRB is explained in four stages that present a progression from porous media
      flow through preferential flow and, finally, complete bypass of the ZVI.

PMID- 16570631
TI  - Improved bioproduction of short-chain fatty acids (SCFAs) from excess sludge
      under alkaline conditions.
AB  - The production of short-chain fatty acids (SCFAs) from excess sludge was
      conducted in batch fermentation tests at different pH values ranging from 4.0 to
      11.0. Experimental results of the impacts of different pHs on SCFAs production
      showed that during the first 8-day fermentation time the total SCFAs production
      at either pH 9.0 or pH 10.0 was much greater than that at acidic or neutral pH,
      and the maximal yield of 256.2 mg SCFAs-COD per gram of volatile suspended solids
      (VSS) was at pH 10.0, which was, respectively, over3 and 4times that at pH 5.0
      and uncontrolled pH. Clearly, SCFAs production from excess sludge could be
      significantly improved and maintained stable by controlling the fermentation pH
      at 10.0. The composition of SCFAs and the percent distribution of individual
      SCFAs accounting for total SCFAs at pH 10.0 were analyzed. The SCFAs consisted of
      acetic, propionic, iso-butyric, n-butyric, iso-valeric, and n-valeric acids, and
      acetic acid was the most prevalent product with a fraction of 40-55%. Because the
      results of this study were differentfrom those of previous studies of SCFAs
      production, the mechanism of increased SCFAs production under alkaline conditions
      was investigated. Results showed that as soluble COD increased, more soluble
      protein was provided as the substrate for producing SCFAs. In addition, less or
      even no SCFAs were consumed by methanogens at alkaline pH, so the SCFAs
      production was therefore remarkably improved. Further investigation revealed
      thatthe formation of SCFA at pH 10.0 was dominated by biological effects rather
      than by chemical hydrolysis.

PMID- 16570632
TI  - Reactivation of an aged commercial three-way catalyst by oxalic and citric acid
      washing.
AB  - The efficiency of dilute oxalic and citric acid solutions on improving the oxygen
      storage capacity (OSC) and catalytic activity of a severely aged (83,000 km)
      commercial three-way catalyst (TWC) has been investigated. Washing procedures
      applied after optimization of experimental parameters, namely, temperature, flow
      rate, and concentration of acid solution, led to significant improvements of OSC
      and catalytic activity (based on dynamometer test measurements) of the aged TWC.
      The latterwas made possible due to the removal of significant amounts of various
      contaminants accumulated on the catalyst surface (e.g., P, S, Pb, Ca, Zn, Si, Fe,
      Cu, and Ni) during driving conditions, as revealed by Inductively Coupled Plasma
      Atomic Emission Spectrometry (ICP-AES) and X-ray Photoelectron Spectroscopy (XPS)
      analyses. For the first time, it is demonstrated that dilute oxalic acid solution
      significantly improves the catalytic activity of an aged commercial TWC toward
      CO, Cx,Hy, and NOx conversions under real exhaust gas conditions (dynamometer
      tests) by two to eight times in the 250-450 degrees C range and the OSC quantity
      by up to 50%. Oxalic acid appears to be more efficient than citric acid in
      removing specifically P- and S-containing compounds from the catalyst surface,
      whereas citric acid in removing Pb- and Zn-containing compounds, thus uncovering
      surface active catalytic sites.

PMID- 16570633
TI  - Investigation of seawater reverse osmosis fouling and its relationship to
      pretreatment type.
AB  - Desalination of seawater using reverse osmosis (RO) technology is an important
      option available to water-scarce coastal regions. A major challenge to seawater
      reverse osmosis (SWRO) is membrane productivity decline due to fouling.
      Systematic studies in the area of SWRO fouling are lacking as compared to RO
      fouling by freshwater. The effect of the type of pretreatment employed ahead of
      the SWRO process has been recognized to be of critical importance in SWRO
      fouling. The objective of this study was to evaluate the effect of pretreatment
      on SWRO performance using bench scale experiments. The effect of different
      pretreatment strategies on SWRO flux decline was simulated using prefiltration of
      the SWRO feedwater using different filtration size ranges. The prefiltration size
      ranges used were selected to mimic the size fractions associated with different
      SWRO pretreatment processes. It was found that particulate matter greater than 1
      microm (representing media filtration) caused most of the RO fouling. On the
      other hand, significant reduction in fouling was observed when membrane
      filtration was used (microfiltration represented by 0.1 microm prefiltration and
      ultrafiltration represented by 100 kDa prefiltration). There was no significant
      difference in flux decline between these two membrane filtration types. The
      lowest RO flux decline was observed when a tight ultrafiltration membrane (20
      kDa) was used as prefiltration. The RO fouling observed was modeled using the gel
      layertheory, which could be used to satisfactorily describe fouling by different
      dissolved fractions of seawater. The observed SWRO fouling trends were confirmed
      using specially adapted attenuated total reflection Fourier transform infrared
      (ATR-FTIR) spectroscopy of the fouled membrane surface.

PMID- 16570635
TI  - Monitoring of vasculogenesis-inhibiting activities in sewage effluents by using
      medaka embryos.
AB  - Environmental samples are known to be contaminated with complex chemicals such as
      estrogens, polycyclic aromatic hydrocarbons, and retinoids. These contaminants
      have potentially an adverse impact on survival of aquatic animals, because we
      found previously that medaka (Oryzias latipes) embryos are defective in the
      development of blood vessels and bones in the presence of these chemicals. Thus,
      it is important to test whether sewage effluents contain inhibitory activities
      against the embryonic development. To examine for such activity, medaka embryos
      were exposed for 48 h to extracts or freeze-evaporated concentrates of effluent
      samples collected from different municipal sewage treatment plants. We used the
      transgenic embryos that are hypersensitive to estrogens due to a high-level
      expression of estrogen receptor for detecting the total (sum of estrogenic and
      non-estrogenic) vessel-inhibiting activity. The embryos were specifically
      defective in blood-vessel formation in most effluent samples, showing the
      activities ranging from 3 to 30 ng of 17beta-estradiol equiv per liter. Detection
      limit of 17beta-estradiol was 10 ng per liter. For detection of the non
      estrogenic vessel-inhibiting activity, we treated the transgenic embryos in the
      presence of an antiestrogen, tamoxifen, or used the wild-type embryos. The non
      estrogenic activities were found in some (7 out of 18) effluents, ranging from
      half to all of the total activities. Our findings for the first time demonstrate
      the utility of the vascular assay for monitoring sewage effluents.

PMID- 16570634
TI  - Arsenic(V) removal from groundwater using nano scale zero-valent iron as a
      colloidal reactive barrier material.
AB  - The removal of As(V), one of the most poisonous groundwater pollutants, by
      synthetic nanoscale zero-valent iron (NZVI) was studied. Batch experiments were
      performed to investigate the influence of pH, adsorption kinetics, sorption
      mechanism, and anionic effects. Field emission scanning electron microscopy (FE
      SEM), high-resolution transmission electron microscopy (HR-TEM), X-ray
      diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Mossbauer
      spectroscopy were used to characterize the particle size, surface morphology, and
      corrosion layer formation on pristine NZVI and As(V)-treated NZVI. The HR-TEM
      study of pristine NZVI showed a core-shell-like structure, where more than 90% of
      the nanoparticles were under 30 nm in diameter. Mossbauer spectroscopy further
      confirmed its structure in which 19% were in zero-valent state with a coat of 81%
      iron oxides. The XRD results showed that As(V)-treated NZVI was gradually
      converted into magnetite/maghemite corrosion products over 90 days. The XPS study
      confirmed that 25% As(V) was reduced to As(III) by NZVI after 90 days. As(V)
      adsorption kinetics were rapid and occurred within minutes following a pseudo
      first-order rate expression with observed reaction rate constants (Kobs) of 0.02
      0.71 min(-1) at various NZVI concentrations. Laser light scattering analysis
      confirmed that NZVI-As(V) forms an inner-sphere surface complexation. The effects
      of competing anions revealed that HCO3-, H4SiO4(0), and H2PO4(2-) are potential
      interfering agents in the As(V) adsorption reaction. Our results suggest that
      NZVI is a suitable candidate for As(V) remediation.

PMID- 16570637
TI  - Toxicity of silver, zinc, copper, and nickel to the copepod Acartia tonsa exposed
      via a phytoplankton diet.
AB  - Toxicity tests were conducted with the marine copepod Acartia tonsa to assess the
      effects of dietary metal exposure. The diatom Thalassiosira pseudonana was
      cultured with Ag, Zn, Cu, or Ni and used as diets for adult A. tonsa over a 7-d
      exposure, and copepod survival and reproduction were measured throughout the
      exposure period. For all metals, reproduction was the most sensitive endpoint,
      with 20% effect concentrations (EC(20)s) corresponding to exposures of T.
      pseudonana to 0.64, 0.3, 1.2, and 2.4 microg/L for Ag, Zn, Cu, and Ni,
      respectively. The corresponding metal concentrations in the algae added to
      copepod test solutions (EC(20)s) were 5.44, 0.55, 22.3, and 15.3 microg/g for Ag,
      Zn, Cu, and Ni, respectively. None of the applied metal concentrations influenced
      algal growth. The results of this study have potential implications for water
      quality criteria considering that the estimated EC(20)s fall below the current
      criteria of 3, 86, 3, and 8.3 microg/L for Ag, Zn, Cu, and Ni, respectively.

PMID- 16570636
TI  - Impairment of cellular immunity in west Greenland sledge dogs (Canis familiaris)
      dietary exposed to polluted minke whale (Balaenoptera acutorostrata) blubber.
AB  - Minke whale (Balaenoptera acutorostrata) blubber is rich in organohalogen
      contaminants, mercury, and n-3 fatty acids. In the present study we show that a
      daily intake of 50-200 g of minke whale blubber causes an impairment of the
      nonspecific and specific cellular immune system in the West Greenland sledge dog
      (Canis familiaris). Immune reactions were measured by mitogen (PHA, Con A) and
      antigen (KLH) intradermal testing, and as the study used exposure levels similar
      to those of Inuits and polar bears (Ursus maritimus), it is reasonable to infer
      that Inuits and polar bears suffer from similar decreased resistance to diseases.
      It is speculated that food sources are depleted by thinning sea ice due to
      climate change and that more research should assess the forecasted rise in
      additive immunopathy effects in polar bears. Additionally, our study suggests
      that the fatty acid composition may be of importance when investigating combined
      immunotoxic effects of contaminated food resources in future Inuit and polar bear
      studies.

PMID- 16570638
TI  - The NBNA: working through barriers to help our own and others survive a crisis.

PMID- 16570639
TI  - Diabetes: a major health disparity for pre-menopausal African-American women.

PMID- 16570640
TI  - Prevalence of hypertension in a sample of Black American adults using JNC 7
      classifications.
AB  - High blood pressure is a major health problem, particularly among Black
      Americans, and many Black Americans are unaware that they have the disease. In
      2003, new guidelines (JNC 7) were created for classifying blood pressure
      including a category designated as "pre-hypertension." We examined the prevalence
      of hypertension based on JNC 7 guidelines in Black Americans from the study of
      Everyday Life for Black American Adults: Stress, Emotional and Cardiovascular
      Responses. In this study, 211 (N = 211) participants had no history of
      hypertension and were not taking anti-hypertensive medications. Demographic
      factors were also explored in relationship to the JNC 7 classifications. Using
      JNC 7, only 28.9% of the participants had normal blood pressures. Of those with
      abnormal blood pressures, 37.8% were pre-hypertensive. Surprisingly, there was a
      high prevalence of hypertension, which might be explained by a lack of awareness
      of their disease status, lack of desire to acknowledge it, or fear of having a
      disease. The pre-hypertension category allows for earlier identification of those
      at risk for developing hypertension so that early interventions can deter its
      debilitating effects.

PMID- 16570642
TI  - Assessing transcultural attitudes towards diabetes in Trinidad.
AB  - The purpose of this descriptive correlational study was to assess diabetic
      attitudes among adults living and working on the Caribbean Island of Trinidad. A
      convenience sample of 66 (N = 66) adult men and women of Afro-Trinidadian
      descent, of Indo-Trinidadian descent, and of mixed ethnicity completed the 33
      item Diabetic Attitude Scale (DAS-3) with its five sub-scales. They were: (1)
      Need for special training in education, (2) Seriousness of Type 2 diabetes, (3)
      Value of tight glucose control, (4) Psychosocial impact of diabetes, and (5)
      Autonomy and patient attitudes. Self-Determination Theory guided the conceptual
      development of the study. Data analyses revealed a strong effect between need for
      special training and autonomy and patient attitudes. Strong correlations were
      also found between seriousness of the disease, value of tight glucose control,
      and psychosocial impact. Moderate correlations were found between the other
      variables of the sub-scales. Practical implications were discussed. Findings
      suggest the need for more appropriate educational and supportive interventions of
      an autonomous nature.

PMID- 16570641
TI  - Symptom experience and self-care strategies among healthy, midlife African
      American women.
AB  - The transition into menopause is an experience that is unique to every woman.
      This experience can encompass anything from an occasional hot flash to complete
      and utter distress. Considerable attention is being paid to African-American
      women as they transition through menopause, but their use of symptom self-care
      strategies is an area that would benefit from further research. Findings from
      this study are part of a larger five-year study exploring biopsychosocial health
      and wellness among diverse midlife women. This report includes identification of
      symptom prevalence, symptom distress, and self-care strategies used by midlife
      African-American women during a six-month time period. Prevalent or severe
      symptoms included fatigue, headaches, cramps, night sweats, and depression. Most
      self-care strategies were "passive" strategies, such as 'faith," "think,"
      "accept," or "value/believe/forgive self". It is recommended that health-care
      providers inquire about other symptoms that might accompany classic vasomotor
      menopausal symptoms and identify "active" self-care strategies that ameliorate
      specific symptoms.

PMID- 16570643
TI  - Evaluating nursing outcomes: a mixed-methods approach.
AB  - Being overweight is regarded as the most common nutritional disorder of children
      and adolescents in the United States. The escalating problem of being overweight
      or being obese in our society indicates the need for treatment strategies that
      encompass an all-inclusive approach. Moreover, these strategies need to be
      comprehensively evaluated for their effectiveness. Nurses are in an excellent
      position to ensure that this occurs. The purpose of this study was to determine
      whether using a mixed-methods approach was an efficacious way to provide a
      comprehensive evaluation of the behavior modification benefits of a weight
      loss/weight management nursing intervention in African-American adolescent girls
      (13-17 years of age). The overall effectiveness of the intervention was evaluated
      by analyzing pre- and post-program measures of weight, body mass index,
      cholesterol, blood pressure, self-esteem, depression, and body image
      (quantitative data); conducting focus groups with mothers of the participants;
      and administering open-ended, written questionnaires to the participants
      (qualitative data). Findings from the quantitative data indicated favorable
      outcomes in weight, blood pressure, cholesterol, body mass index, self-esteem,
      and body image, indicating that progress had been made over the course of the
      program. Furthermore, qualitative data indicated that mothers of the participants
      observed positive behavioral changes related to eating and exercise patterns and
      participants demonstrated perception of these changes as well.

PMID- 16570644
TI  - Nursing contributions to the elimination of health disparities among African
      Americans: review and critique of a decade of research--Part III.
AB  - The excessive burden of disease experienced by African-Americans has long been
      described by authorities in the public, private, and professional sector as a
      national health concern. Several reports have been published in the peer-reviewed
      literature that describe the outcomes of nurse-directed studies aimed at
      addressing the factors associated with the disparities experienced by African
      Americans and these reports were also aimed toward the design of interventions to
      reduce and/or eliminate them. However, little is known about the scope, quality,
      and impact of these efforts relative to the promotion of health and the
      prevention of disease among African-American population groups. This report
      presents the results of a review, analysis, and critique of reports of outcomes
      of nursing research aimed toward reducing health-related disparities among
      African-Americans. These reports were described in a selected group of African
      American nursing organizations and journals dedicated to providing a forum for
      the discussion of issues focused on cultural diversity, transcultural nursing,
      and multicultural health care issues. Included among the journals were the
      Journal of the National Black Nurses Association, the Journal of the Association
      of Black Nursing Faculty, the Journal of Chi Eta Phi Sorority, the Journal of
      Cultural Diversity, the Journal of Transcultural Nursing, and the Journal of
      Multicultural Nursing and Health. Results of the review will be reported in three
      parts. The first part was reported in an earlier edition (Journal of National
      Black Nurses Association, Volume 15, No. 1), the second part was reported in
      Volume 16, No 1, of the Journal of National Black Nurses Association, and the
      third part is reported here. The results of this critique revealed that this body
      of nursing research provides the profession with a broad base of knowledge and
      insights. This knowledge is relative to the individual and familial impact of
      cardiovascular disease, cancer, diabetes, HIV/AIDS, mental health and mental
      illness, and sickle cell disease within the African-American community. Knowledge
      and insights relative to the concerns and needs of childbearing, parenting, the
      elderly caregivers and care giving in African-American population groups is
      essential if health care disparities are to be truly eliminated. This review,
      analysis, and critique also revealed several gaps and limitations within this
      body of nursing research.

PMID- 16570645
TI  - [Cardiomyopathy].

PMID- 16570646
TI  - [Health economic consequences of the use of irbesartan in patients with type 2
      diabetes, hypertension and nephropathy in Switzerland].
AB  - The irbesartan in Diabetic Nephropathy Trial (IDNT) demonstrated that treatment
      of patients with type 2 diabetes, hypertension and nephropathy with irbesartan
      resulted in a 20% relative reduction of the composite endpoint of doubling serum
      creatinine, end-stage renal disease or death as compared with amlodipine and
      placebo (antihypertensive standard therapy). The objective of this study was to
      investigate the long-term health economic consequences of this treatment strategy
      in a Swiss health care setting. This analysis used a Markov model to simulate the
      progression of nephropathy, life-years and treatment costs over ten years for
      each of the three treatment options. In additon, sensitivity analyses were
      performed. Treatment with irbesartan will save CHF 22681/patient as compared with
      amlodipine and CHF 13847 as compared with standard therapy.

PMID- 16570647
TI  - [AB0 incompatible transplantation: top or flop?].

PMID- 16570648
TI  - [Comments on the case: "please stop the painful artificial nutrition!"].

PMID- 16570649
TI  - [Pericardial effusion in a 21-year-old employee].

PMID- 16570650
TI  - [Unclear epigastric pain].

PMID- 16570651
TI  - [Right-sided hypogastric pain].

PMID- 16570653
TI  - Long- and short-chain plant-produced bacterial N-acyl-homoserine lactones become
      components of phyllosphere, rhizosphere, and soil.
AB  - Two N-acyl-homoserine lactone (acyl-HSL) synthase genes, lasI from Pseudomonas
      aeruginosa and yenI from Yersinia enterocolitica, were introduced into tobacco,
      individually and in combination. Liquid chromatograph-tandem mass spectrometry
      and thin-layer chromatography confirmed products of lasI and yenI activity in
      single and cotransformants. Cotransformants expressing plastid-localized LasI and
      YenI synthases produced the major acyl-HSLs for each synthase in all tissues
      tested. Total acyl-HSL signals accumulated in leaf tissue up to 3 pmol/mg of
      fresh weight, half as much in stem tissue, and approximately 10-fold less in root
      tissues. Acyl-HSLs were present in aqueous leaf washes from greenhouse-grown
      transgenic plants. Transgenic lines grown for 14 days under axenic conditions
      produced detectable levels of acyl-HSLs in root exudates. Ethyl acetate
      extractions of rhizosphere and nonrhizosphere soil from transgenically grown
      plants contained active acyl-HSLs, whereas plant-free soil or rhizosphere and
      nonrhizosphere soil from wild-type plants lacked detectable amounts of acyl-HSLs.
      This work shows that bioactive acyl-HSLs are exuded from leaves and roots and
      accumulate in the phytosphere of plants engineered to produce acyl-HSLs. These
      data further suggest that plants that are bioengineered to synthesize acyl-HSLs
      can foster beneficial plant-bacteria communications or deter deleterious
      interactions. Therefore, it is feasible to use bioengineered plants to supplement
      soils with specific acyl-HSLs to modulate bacterial phenotypes and plant
      associated bacterial community structures.

PMID- 16570652
TI  - The production of species-specific highly unsaturated fatty acyl-containing LCOs
      from Rhizobium leguminosarum bv. trifolii is stringently regulated by nodD and
      involves the nodRL genes.
AB  - A proportion of the Nod factors of some Rhizobium leguminosarum bv. trifolii
      strains is characterized by the presence of highly unsaturated fatty acyl chains
      containing trans double bonds in conjugation with the carbonyl group of the
      glycan oligosaccharide backbone. These fatty acyl chains are C18:3, C20:3, C18:4,
      or C20:4 and have UV-absorption maxima at 303 and 330 nm. These Nod factors are
      presumed to be important for host-specific nodulation on clover species. However,
      in wild-type R. leguminosarum bv. trifolii ANU843, Nod factors with these
      characteristic acyl chains were not observed using standard growth conditions.
      They were observed only when nod genes were present in multiple copies or when
      transcription was artificially increased to higher levels by introduction of
      extra copies of the transcriptional regulator gene nodD. In a screen for the
      genetic requirements for production of the Nod factors with these characteristic
      structures, it was found that the region downstream of nodF and nodE is essential
      for the presence of highly unsaturated fatty acyl moieties. Mu-lacZ insertion in
      this region produced a mutant that did not produce detectable levels of the
      highly unsaturated fatty acyl-bearing Nod factors. The Mu-lacZ insertion was
      translationally fused to a putative new gene, designated nodR, in the nodE-nodL
      intergenic region; however, no predicted function for the putative NodR protein
      has been obtained from database homology searches. In a set of 12 wild-type
      strains of R. leguminosarum by. trifolii originating from various geographical
      regions that were analyzed for the presence of a nodR-like gene, it was found
      that seven strains carry a homologous NodR open reading frame. Taken together,
      our results suggest a tightly controlled regulation of nod genes, in which we
      propose that it is the balance of transcriptional levels of nodFE and the nodRL
      genes that is critical for determining the presence of highly unsaturated fatty
      acyl moieties in the Nod factors produced by R. leguminosarum bv. trifolii.

PMID- 16570654
TI  - Inhibition of resistance gene-mediated defense in rice by Xanthomonas oryzae pv.
      oryzicola.
AB  - Xanthomonas oryzae pv. oryzae and the closely related X. oryzae pv. oryzicola
      cause bacterial blight and bacterial leaf streak of rice, respectively. Although
      many rice resistance (R) genes and some corresponding avirulence (avr) genes have
      been characterized for bacterial blight, no endogenous avr/R gene interactions
      have been identified for leaf streak. Genes avrXa7 and avrXa10 from X. oryzae pv.
      oryzae failed to elicit the plant defense-associated hypersensitive reaction (HR)
      and failed to prevent development of leaf streak in rice cultivars with the
      corresponding R genes after introduction into X. oryzae pv. oryzicola despite the
      ability of this pathovar to deliver an AvrXa10:Cya fusion protein into rice
      cells. Furthermore, coinoculation of X. oryzae pv. oryzicola inhibited the HR of
      rice cultivar IRBB10 to X. oryzae pv. oryzae carrying avrXa10. Inhibition was
      quantitative and dependent on the type III secretion system of X. oryzae pv.
      oryzicola. The results suggest that one or more X. oryzae pv. oryzicola type III
      effectors interfere with avr/R gene-mediated recognition or signaling and
      subsequent defense response in the host. Inhibition of R gene-mediated defense by
      X. oryzae pv. oryzicola may explain, in part, the apparent lack of major gene
      resistance to leaf streak.

PMID- 16570655
TI  - Organic acids, sugars, and L-tryptophane in exudates of vegetables growing on
      stonewool and their effects on activities of rhizosphere bacteria.
AB  - The influence of stonewool substrate on the exudation of the major soluble carbon
      nutrients and of the auxin precursor tryptophane for Pseudomonas biocontrol
      agents was studied. To this end, the composition of the organic acids and sugars,
      as well that of tryptophane, of axenically collected exudates of seed, seedlings,
      and roots of tomato, cucumber, and sweet pepper was determined. The major results
      were as follows. i) The total amount of organic acid is much higher than that of
      total sugar. ii) Exudation of both organic acids and sugars increases during
      plant growth. iii) Citric, succinic, and malic acids represent the major organic
      acids, whereas fructose and glucose are the major sugars. iv) Compared with glass
      beads as a neutral substrate, stonewool substantially stimulates exudation of
      organic acids and sugars. v) It appeared that enhanced root-tip-colonizing
      bacteria isolated previously from the rhizosphere of tomato and cucumber grow
      much better in minimal medium with citrate as the sole carbon source than other,
      randomly selected rhizobacteria do. This indicates that the procedure which
      selects for excellent root-tip colonizers enriches for strains which utilize the
      major exudate carbon source citrate. vi) The content of L-tryptophane, the direct
      precursor of auxin, is approximately 60-fold higher in seedling exudates of
      tomato and sweet pepper than in cucumber seedling exudates, indicating a higher
      possibility of plant growth stimulation after inoculation with auxin-producing
      rhizobacteria for tomato and sweet pepper crops than for cucumber. However, the
      biocontrol strain Pseudomonas fluorescens WCS365, which is able to convert
      tryptophane into auxin, did not stimulate growth of these three crops. In
      contrast, this strain did stimulate growth of roots of radish, a plant which
      exudes nine times more tryptophane than tomato does.

PMID- 16570656
TI  - The expression of genes encoding lipodepsipeptide phytotoxins by Pseudomonas
      syringae pv. syringae is coordinated in response to plant signal molecules.
AB  - Specific plant signal molecules are known to induce syringomycin production and
      expression of syrB1, a syringomycin synthetase gene, in Pseudomonas syringae pv.
      syringae. This report demonstrates that syringopeptin production likewise is
      activated by plant signal molecules and that the GacS, SalA, and SyrF regulatory
      pathway mediates transmission of plant signal molecules to the syr-syp
      biosynthesis apparatus. Syringopeptin production by BR132 was increased two-fold
      by addition of arbutin (100 microM) and D-fructose (0.1%) to syringomycin minimal
      medium (SRM). Among 10 plant phenolic compounds tested, only the phenolic
      glucosides arbutin, salicin, and phenyl-beta-D-glucopyranoside induced
      substantially the beta-glucuronidase (GUS) activity of a sypA::uidA reporter from
      242 U per 10(8) CFU without plant signal molecules up to 419 U per 10(8) CFU with
      plant signal molecules. Syringopeptin production was found to be controlled by
      the SalA/SyrF regulon because no toxin was detected from cultures of B301DSL7
      (i.e., salA mutant) and B301DSL1 (i.e., syrF mutant), and the expression of
      sypA::uidA was decreased approximately 99 and 94% in salA (B301DSL30) and syrF
      (B301DNW31) mutant backgrounds, respectively. Subgenomic analysis of
      transcriptional expression with a 70-mer oligonucleotide microarray demonstrated
      that the syr-syp genes are induced 2.5- to 10.5-fold by addition of arbutin and D
      fructose to SRM. This study establishes that plant signal molecules are
      transmitted through the GacS, SalA/SyrF pathway to activate the coordinated
      transcriptional expression of the syr-syp genes.

PMID- 16570657
TI  - Nonhost resistance in Arabidopsis-Colletotrichum interactions acts at the cell
      periphery and requires actin filament function.
AB  - Pathogenesis of nonadapted fungal pathogens is often terminated coincident with
      their attempted penetration into epidermal cells of nonhost plants. The genus
      Colletotrichum represents an economically important group of fungal plant
      pathogens that are amenable to molecular genetic analysis. Here, we investigated
      interactions between Arabidopsis and Colletotrichum to gain insights in plant and
      pathogen processes activating nonhost resistance responses. Three tested
      nonadapted Colletotrichum species differentiated melanized appressoria on
      Arabidopsis leaves but failed to form intracellular hyphae. Plant cells responded
      to Colletotrichum invasion attempts by the formation of PMR4/GSL5-dependent
      papillary callose. Appressorium differentiation and melanization were
      insufficient to trigger this localized plant cell response, but analysis of
      nonpathogenic C. lagenarium mutants implicates penetration-peg formation as the
      inductive cue. We show that Arabidopsis PEN1 syntaxin controls timely
      accumulation of papillary callose but is functionally dispensable for effective
      preinvasion (penetration) resistance in nonhost interactions. Consistent with
      this observation, green fluorescent protein-tagged PEN1 did not accumulate at
      sites of attempted penetration by either adapted or nonadapted Colletotrichum
      species, in contrast to the pronounced focal accumulations of PEN1 associated
      with entry of powdery mildews. We observed extensive reorganization of actin
      microfilaments leading to polar orientation of large actin bundles towards
      appressorial contact sites in interactions with the nonadapted Colletotrichum
      species. Pharmacological inhibition of actin filament function indicates a
      functional contribution of the actin cytoskeleton for both preinvasion resistance
      and papillary callose formation. Interestingly, the incidence of papilla
      formation at entry sites was greatly reduced in interactions with C. higginsianum
      isolates, indicating that this adapted pathogen may suppress preinvasion
      resistance at the cell periphery.

PMID- 16570658
TI  - Cloning and characterization of pectate lyases expressed in the esophageal gland
      of the pine wood nematode Bursaphelenchus xylophilus.
AB  - Two pectate lyase genes (Bx-pel-1 and Bx-pel-2) were cloned from the pine wood
      nematode, Bursaphelenchus xylophilus. The deduced amino acid sequences of these
      pectate lyases are most similar to polysaccharide lyase family 3 proteins.
      Recombinant BxPEL1 showed highest activity on polygalacturonic acid and lower
      activity on more highly methylated pectin. Recombinant BxPEL1 demonstrated full
      dependency on Ca2+ for activity and optimal activity at 55 degrees C and pH 8 to
      10 like other pectate lyases of polysaccharide lyase family 3. The protein
      sequences have predicted signal peptides at their N-termini and the genes are
      expressed solely in the esophageal gland cells of the nematode, indicating that
      the pectate lyases could be secreted into plant tissues to help feeding and
      migration in the tree. This study suggests that pectate lyases are widely
      distributed in plant-parasitic nematodes and play an important role in plant
      nematode interactions.

PMID- 16570659
TI  - Pervasive purifying selection characterizes the evolution of I2 homologs.
AB  - We sampled 384 sequences related to the Solanum pimpinellifolium (=Lycopersicon
      pimpinellifolium) disease resistance (R) gene 12 from six species, potato, S.
      demissum, tomato, eggplant, pepper, and tobacco. These species represent
      increasing phylogenetic distance from potato to tobacco, within the family
      Solanaceae. Using sequence data from the nucleotide binding site (NBS) region of
      this gene, we tested models of gene family evolution and inferred patterns of
      selection acting on the NBS gene region and I2 gene family. We find that the I2
      family has diversified within the family Solanaceae for at least 14 million years
      and evolves through a slow birth-and-death process requiring approximately 12
      million years to homogenize gene copies within a species. Analyses of selection
      resolved a general pattern of strong purifying selection acting on individual
      codon positions within the NBS and on NBS lineages through time. Surprisingly, we
      find nine codon positions strongly affected by positive selection and six pairs
      of codon positions demonstrating correlated amino acid substitutions.
      Evolutionary analyses serve as bioinformatic tools with which to sort through the
      vast R gene diversity in plants and find candidates for new resistance
      specificities or to identify specific amino acid positions important for
      biochemical function. The slow birth-and-death evolution of I2 genes suggests
      that some NBS-leucine rich repeat-mediated resistances may not be overcome
      rapidly by virulence evolution and that the natural diversity of R genes is a
      potentially valuable source for durable resistance.

PMID- 16570660
TI  - Pseudomonas syringae effector avrB confers soybean cultivar-specific avirulence
      on Soybean mosaic virus adapted for transgene expression but effector avrPto does
      not.
AB  - Soybean mosaic virus (SMV) was adapted for transgene expression in soybean and
      used to examine the function of avirulence genes avrB and avrPto of Pseudomonas
      syringae pvs. glycinea and tomato, respectively. A cloning site was introduced
      between the P1 and HC-Pro genes in 35S-driven infectious cDNAs of strains SMV-N
      and SMV-G7. Insertion of the uidA gene or the green fluorescent protein gene into
      either modified cDNA and bombardment into primary leaves resulted in systemic
      expression that reflected the pattern of viral movement into uninoculated leaves.
      Insertion of avrB blocked symptom development and detectable viral movement in
      cv. Harosoy, which carries the Rpg1-b resistance gene corresponding to avrB, but
      not in cvs. Keburi or Hurrelbrink, which lack Rpg1-b. In Keburi and Hurrelbrink,
      symptoms caused by SMV carrying avrB appeared more quickly and were more severe
      than those caused by the virus without avrB. Insertion of avrPto enhanced
      symptoms in Harosoy, Hurrelbrink, and Keburi. This result was unexpected because
      avrPto was reported to confer avirulence on P. syringae pv. glycinea inoculated
      to Harosoy. We inoculated Harosoy with P syringae pv. glycinea expressing avrPto,
      but observed no hypersensitive reaction, avrPto-dependent induction of
      pathogenesis-related protein la, or limitation of bacterial population growth. In
      Hurrelbrink, avrPto enhanced bacterial multiplication and exacerbated symptoms.
      Our results establish SMV as an expression vector for soybean. They demonstrate
      that resistance triggered by avrB is effective against SMV, and that avrB and
      avrPto have general virulence effects in soybean. The results also led to a
      reevaluation of the reported avirulence activity of avrPto in this plant.

PMID- 16570661
TI  - Two novel MvaT-like global regulators control exoproduct formation and biocontrol
      activity in root-associated Pseudomonas fluorescens CHA0.
AB  - Pseudomonas fluorescens CHA0 protects various crop plants against root diseases
      caused by pathogenic fungi. Among a range of exoproducts excreted by strain CHA0,
      the antifungal compounds 2,4-diacetylphloroglucinol (DAPG) and pyoluteorin (PLT)
      are particularly relevant to the strain's biocontrol potential. Here, we report
      on the characterization of MvaT and MvaV as novel regulators of biocontrol
      activity in strain CHA0. We establish the two proteins as further members of an
      emerging family of MvaT-like regulators in pseudomonads that are structurally and
      functionally related to the DNA-binding protein H-NS. In mvaT and mvaV in frame
      deletion mutants of strain CHA0, PLT production was enhanced about four- and 1.5
      fold, respectively, whereas DAPG production remained at wild-type levels.
      Remarkably, PLT production was increased up to 20-fold in an mvaT mvaV double
      mutant. DAPG biosynthesis was almost completely repressed in this mutant. The
      effects on antibiotic production could be confirmed by following expression of
      gfp-based reporter fusions to the corresponding biosynthetic genes. MvaT and MvaV
      also influenced levels of other exoproducts, motility, and physicochemical cell
      surface properties to various extents. Compared with the wild type, mvaT and mvaV
      mutants had an about 20% reduced capacity (in terms of plant fresh weight) to
      protect cucumber from a root rot caused by Pythium ultimum. Biocontrol activity
      was nearly completely abolished in the double mutant Our findings indicate that
      MvaT and MvaV act together as further global regulatory elements in the complex
      network controlling expression of biocontrol traits in plant-beneficial
      pseudomonads.

PMID- 16570662
TI  - Insights into symbiotic nitrogen fixation in Medicago truncatula.
AB  - In silico analysis of the Medicago truncatula gene index release 8.0 at The
      Institute for Genomic Research identified approximately 530 tentative consensus
      sequences (TC) clustered from 2,700 expressed sequence tags (EST) derived solely
      from Sinorhizobium meliloti-inoculated root and nodule tissues. A great majority
      (76%) of these TC were derived exclusively from nitrogen-fixing and senescent
      nodules. A cDNA filter array was constructed using approximately 58% of the in
      silico-identified TC as well as cDNAs representing selected carbon and nitrogen
      metabolic pathways. The purpose of the array was to analyze transcript abundance
      in M. truncatula roots and nodules following inoculation by a wild-type S.
      meliloti strain, a mutant strain that forms ineffective nodules, an uninoculated
      root control, and roots following nitrate or ammonium treatments. In all, 81
      cDNAs were upregulated in both effective and ineffective nodules, and 78% of
      these cDNAs represent in silico-identified TC. One group of in silico-identified
      TC encodes genes with similarity to putative plant disease resistance (R) genes
      of the nucleotide binding site-leucine-rich repeat type. Expression of R genes
      was enhanced in effective nodules, and transcripts also were detected in
      ineffective nodules at 14 days postinoculation (dpi). Homologous R gene sequences
      also have been identified in the Medicago genome. However, their functional
      importance in nodules remains to be established. Genes for enzymes involved in
      organic acid synthesis along with genes involved in nitrogen metabolism were
      shown to be coexpressed in nitrate-fed roots and effective nodules of M.
      truncatula.

PMID- 16570663
TI  - Suppression of defense response in plants by the avrBs3/pthA gene family of
      Xanthomonas spp.
AB  - Effector genes of some plant-pathogenic bacteria, including some members of the
      avrBs3/pthA effector gene family from Xanthomonas spp., confer not only genotype
      specific disease resistance but also pathogen aggressiveness or virulence. In
      addition, some effector gene products suppress induction of a nonspecific (or
      general) hypersensitive response (HR). To determine whether the Xanthomonas
      avrBs3/pthA gene family members apl1, avrXa7, or avrXa10 also confer suppressor
      activity, we introduced constructs with each effector gene into Pseudomonas
      fluorescens 55 that expressed the entire hrp cluster from P. syringae pv.
      syringae in cosmid pHIR11. When inoculated to tobacco 'Bright Yellow', P
      fluorescens (pHIR11) induces the HR and expression of four tobacco defense
      response genes: HIN1, RbohB, PAL, and PR1. When P. fluorescens double
      transformants that contained pHIR11 and constructs with apl1, avrXa7, or avrXa10
      were infiltrated into tobacco, the HR and expression of three defense response
      genes, RbohB, PAL, and PR1, were suppressed. The suppression of the HR and
      defense gene expression was more efficient in the transformants with the apl1 and
      avrXa7 than the transformant with avrXa10. Although expression of other defense
      genes was suppressed by the double transformants, HIN1 expression was the same
      level as was observed after infiltration with P. fluorescens (pHIR11), suggesting
      that HIN1 may not be involved directly in HR. Taken together, our data suggest
      that avrXa7, avrXa10, and apl1, when delivered to plant cells by the P. syringae
      pv. syringae hrp secretion system, can suppress nonhost HR and associated
      phenotypes.

PMID- 16570664
TI  - Identification of a plum pox virus CI-interacting protein from chloroplast that
      has a negative effect in virus infection.
AB  - The cylindrical inclusion (CI) protein of potyviruses is involved in virus
      replication and cell-to-cell movement. These two processes should rely on
      multiple plant-virus interactions; however, little is known about the host
      factors that are involved in, or that may interfere with, CI functions. By using
      a yeast two-hybrid system, the CI protein from Plum pox virus (PPV) was found to
      interact with the photosystem I PSI-K protein, the product of the gene psaK, of
      Nicotiana benthamiana. Coexpression of PPV CI was shown to cause a decrease in
      the accumulation level of PSI-K transiently expressed in N. benthamiana leaves.
      To test the biological relevance of this interaction, we have analyzed the
      infection of PPV in N. benthamiana plants in which psaK gene expression has been
      silenced by RNA interference, as well as in Arabidopsis thaliana psaK knockout
      plants. Our results show that downregulation of the psaK gene leads to higher PPV
      accumulation, suggesting a role for the CI-PSI-K interaction in PPV infection.

PMID- 16570665
TI  - Families play safe in the sun.

PMID- 16570666
TI  - What's eating you? Trichuris trichiura (human whipworm).

PMID- 16570667
TI  - A patch test study to evaluate the allergenicity of a metallic jewelry alloy in
      patients allergic to cobalt.
AB  - Cobalt is a common inducer of allergic contact dermatitis. A new jewelry alloy
      containing cobalt was developed and tested on 30 individuals with documented
      allergy to cobalt. Of these subjects, 5 (18%) were found to be allergic to the
      new alloy after 7 or 8 days of exposure. In all cases, the reaction was much less
      severe than allergy to the 1% cobalt chloride patch test material. This new alloy
      should be better tolerated by individuals allergic to cobalt, perhaps because the
      cobalt is tightly bound in the alloy by the other main component, platinum.

PMID- 16570668
TI  - What is your diagnosis? Disseminated coccidioidomycosis.

PMID- 16570669
TI  - Neonatal lupus erythematosus.
AB  - Neonatal lupus erythematosus (NLE) is a rare syndrome of newborns and infants
      defined by the presence of maternal autoantibodies and the characteristic
      clinical features of the infant. The clinical findings most often reported are
      congenital heart block and cutaneous lesions; however, many children have
      cardiomyopathy, hepatobiliary disease, and/or hematologic diatheses. We present
      the case of a 1-day-old African American boy who presented with an annular,
      ulcerated facial eruption at birth and went on to develop subacute cutaneous LE
      (SCLE) and heart block.

PMID- 16570670
TI  - Henoch-Schonlein purpura presenting with orchitis: a case report and review of
      the literature.
AB  - Henoch-Schonlein purpura (HSP) is the most common cause of nonthrombocytopenic
      purpura in children. The clinical picture is classically a cutaneous purpuric
      eruption of the legs and buttocks and infrequently the upper torso and
      extremities. Arthritis, gastrointestinal tract symptoms, and nephritis are other
      common findings typically associated with the cutaneous findings. We present an
      unusual case of HSP with scrotal swelling and orchitis.

PMID- 16570671
TI  - Tinea capitis: current concepts in clinical practice.
AB  - Tinea capitis is a common infection, particularly among young children in urban
      regions. The infection often is seen in a form with mild scaling and little hair
      loss, a result of the prominence of Trichophyton tonsurans (the most frequent
      cause of tinea capitis in the United States). T. tonsurans does not fluoresce
      under Wood light, unlike the common tinea capitis-causing fungal organisms seen
      in Europe and many other countries, which emit a green fluorescence. However, T.
      tonsurans, like other fungi, also may less often produce an intense inflammatory
      reaction, which is suggestive of an acute bacterial infection.

PMID- 16570672
TI  - Successful treatment of auricular pseudocyst using a surgical bolster: a case
      report and review of the literature.
AB  - Auricular pseudocysts are a benign condition characterized by the asymptomatic,
      usually unilateral swelling of the helix or antihelix. The condition is often
      difficult to treat because recurrences and subsequent auricular deformities are
      common. We successfully treated a patient with an auricular pseudocyst of the
      left ear using needle aspiration followed by application of a surgical bolster.
      In this article, we discuss the features of auricular pseudocysts and propose a
      simple, first-line approach to the management of this disease.

PMID- 16570673
TI  - Scalp metastasis from esophageal adenocarcinoma.
AB  - There are few reported cases of cutaneous metastases of esophageal carcinoma,
      especially of esophageal adenocarcinoma, but reports may become more common as
      the incidence of esophageal cancer increases. We present a case of a 67-year-old
      man with metastatic esophageal cancer in the scalp. Clinical and histologic
      findings are discussed, and recommendations for clinicians are suggested.

PMID- 16570674
TI  - Apparent response of cutaneous Merkel cell tumor to topical imiquimod.

PMID- 16570675
TI  - Topical miconazole nitrate ointment in the treatment of diaper dermatitis
      complicated by candidiasis.
AB  - Diaper dermatitis (DD) complicated by candidiasis is a common problem in diaper
      wearing infants and children. We report a double-blind, vehicle-controlled,
      parallel-group study evaluating the efficacy and safety of a low concentration of
      miconazole nitrate in a zinc oxide/petrolatum ointment for the treatment of DD
      complicated by candidiasis. Patients (N=330) who had DD with a severity score of
      3 or higher were enrolled. Those patients with a baseline potassium hydroxide
      (KOH) preparation and a baseline culture specimen that both tested positive for
      Candida were retained for efficacy analysis (n=236). Miconazole nitrate 0.25%
      ointment or a zinc oxide/petrolatum vehicle control were applied to all
      clinically affected areas of patients with DD for 7 days at each diaper change
      and after bathing. A follow-up test-of-cure visit was conducted at day 14. Among
      the patients completing the study, the overall rate of cure (clinical cure plus
      microbiologic cure) was 23% for the miconazole nitrate group and 10% for the
      vehicle control group (P=.005); the rate of clinical cure (complete rash
      clearance, DD severity score=0 at day 14) was 38% for the miconazole nitrate
      group and 11% for the vehicle control group (P<.001); and the rate of
      microbiologic cure (no culture growth of Candida) was 50% for the miconazole
      nitrate group and 23% for the vehicle control group. The vehicle control resulted
      in mild improvement at day 3 but little or no subsequent improvement. The
      discontinuation rate due to clinical failure was substantially lower for the
      miconazole nitrate group (4%) than the vehicle control group (47%). The mean DD
      severity index score for the miconazole nitrate group was significantly lower
      from day 3 through day 14 compared with that of the vehicle control group
      (P<.001). Adverse events were assessed as either unlikely to be related to study
      medication or unrelated to study medication. By including only those patients
      with microbiologically confirmed Candida infection, the study population may not
      be fully indicative of patients treated for DD in routine clinical practice. Our
      data show that miconazole nitrate 0.25% ointment was well tolerated and
      significantly more effective than the zinc oxide/petrolatum vehicle control for
      treatment of DD complicated by candidiasis.

PMID- 16570676
TI  - Registering clinical trials in India.

PMID- 16570677
TI  - Gastroduodenal dysmotility in patients with gallbladder carcinoma: frequency of
      occurrence and clinical importance.
AB  - BACKGROUND: Gastric stasis, common in patients with gall-bladder carcinoma (GBC),
      results from anatomical obstruction or motor abnormalities. We studied patients
      with GBC for antroduodenal motor dysfunction using manometry. METHODS: Forty-one
      patients with GBC without endoscopic gastric outlet obstruction and 10 healthy
      controls were evaluated using a symptom scoring system for gastric stasis, saline
      load test and water perfusion antroduodenal manometry. Fasting, post-prandial and
      post-octreotide motility were recorded and analysed on a computer using GiPC
      manometry software. RESULTS: Sixteen of 41 patients (39%) with GBC reported
      recurrent vomiting; patients with vomiting had a higher symptom score (13 [11-17]
      v. 6 [4-10], p<0.0001] and higher volume of aspirate on the saline load test (460
      ml [210-650] v. 160 ml [70-260], p<0.0001) as compared with those without
      vomiting. Healthy subjects more often had spontaneous fasting migratory motor
      complex than patients with GBC (9/10 v. 13/41, p=0.002). The amplitudes of
      contractions in the antrum and duodenum were significantly lower in patients with
      GBC than in healthy subjects. Patients with GBC had lower fasting (157 [68-284]
      v. 190.5 [150-284], p=0.01) and post-prandial (200 [96-395] v. 284 [178-395],
      p<0.0001) antral motor indices than healthy subjects. Patients with GBC and
      vomiting had significantly lower contraction amplitude and motility indices than
      those without vomiting. Motility indices correlated inversely with the symptom
      score and volume of aspirate on the saline load test (Spearman correlation, p =
      0.01 for all). CONCLUSION: Antroduodenal motor abnormalities are common in
      patients with GBC. These may explain the symptoms of gastric stasis and abnormal
      results of the saline load test in the absence of anatomical obstruction in such
      patients.

PMID- 16570678
TI  - Rate of hospitalization and inpatient care costs for HIV-1-infected patients in
      Pune, India.
AB  - BACKGROUND: The transition of human immunodeficiency virus (HIV) infection to
      acquired immune deficiency syndrome (AIDS) has begun in India, and an increase in
      AIDS-related hospitalizations and deaths is an anticipated challenge. We
      estimated the rates of hospitalization and inpatient care costs for HIV-1
      infected patients. METHODS: Data were analysed on 381 HIV-1-infected persons
      enrolled in a HIV-1 discordant couples' cohort between September 2002 and March
      2004. Inpatient care costs were extracted from select hospitals where the study
      patients were hospitalized and the average cost per hospitalization was
      calculated. RESULTS: A majority of the patients were in an advanced state of HIV
      1 disease with the median CD4 counts being 207 cells/cmm (range: 4-1131
      cells/cmm). In all, 63 participants who did not receive antiretroviral therapy
      required hospitalization, 53 due to HIV-1-related illnesses and the remaining 10
      due to worsening of pre-existing conditions. The overall HIV-1-related
      hospitalization rate was 34.2 per 100 person-years (95% CI: 26.94-42.93). The
      median duration of HIV-1-related hospitalization was 10 days (range 2-48 days)
      and the median cost was Rs 17,464 (range: Rs 400-63,891). CONCLUSION: It is
      necessary to strengthen the inpatient care infrastructure and supporting
      diagnostic set-up, and work out economically optimized treatment algorithms for
      HIV-1-infected patients. Although this analysis does not cover all costs and may
      not be generalizable, these baseline data might be a useful reference while
      planning related studies accompanying the government-sponsored programme to roll
      out antiretroviral therapy to AIDS patients.

PMID- 16570679
TI  - Usefulness of an observational database to assess antiretroviral treatment trends
      in India.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) observational cohorts, which are
      established worldwide, support comparative studies across different regions. They
      have played an important role in developing international and country-specific
      HIV treatment and care guidelines. We describe the YRG CARE Chennai HIV
      observation database (YCHOD) and highlight its utility in monitoring trends in
      antiretroviral treatment use and HIV disease outcomes in India. METHODS: The
      baseline characteristics, time trends in antiretroviral treatment, trends in
      incidence of acquired immune deficiency syndrome (AIDS)-defining illness and
      mortality following the introduction of highly active antiretroviral therapy
      (HAART) in India were assessed using YCHOD. RESULTS: Till January 2005, 7647 HIV
      positive patients had registered in YCHOD. A majority of the patients were men
      (69%) and had a mean age of 32 years. At baseline, 14% had an existing AIDS
      defining illness. Among patients who required therapy by the WHO criteria, 14%
      initiated antiretroviral therapy (ART) in 1996 and 35% in 2000. Since the
      dramatic cost reduction of generic HAART in 2001, there has been an increase in
      the proportion of patients receiving ART to 57% in 2004. In patients who were
      started on HAART, the incidence of at least one AIDS-defining illness was 2% in
      2001, and this decreased to 0.48% in 2004. CONCLUSION: We feel observational
      cohorts are useful as a surveillance tool for monitoring trends in treatment and
      disease progression. Standardized observational data collected systematically on
      HIV-infected individuals will help to assess the cost-effectiveness of ART and in
      planning ART strategies for India.

PMID- 16570680
TI  - Role of testicular fine-needle aspiration cytology in infertile men with
      clinically obstructive azoospermia.
AB  - BACKGROUND: Azoospermia due to obstruction of the vaso-epididymal junction is one
      of the few surgically correctable causes of male infertility. In patients where
      all clinical and laboratory parameters suggest a vaso-epididymal junction block
      amenable to surgery, failure to find normal spermatogenesis on fine-needle
      aspiration cytology (FNAC) of the testis may necessitate a change in treatment
      modality to the more expensive intracytoplasmic sperm injection. We evaluated the
      validity of FNAC findings in predicting failure of surgical exploration when
      clinical parameters suggest otherwise. METHODS: Infertile, azoospermic men in
      whom the semen volume and fructose content, testis size, follicle-stimulating
      hormone level were normal and the vas deferens was palpable with no evident cause
      for obstruction, underwent FNAC of the testis to confirm the presence of normal
      spermatogenesis before surgical exploration. Men with hypospermatogenesis or
      maturation arrest on FNAC and a normal karyotype with absence of Y chromosome
      microdeletion were offered assisted reproduction or surgical exploration to
      identify a reconstructable obstruction. Men who chose surgery were included in
      the study and the findings on exploration were compared with the FNAC reports.
      RESULTS: Of the 10 men who satisfied the inclusion criteria, 6 had
      hypospermatogenesis and in 4 FNAC showed maturation arrest. On surgical
      exploration, none had sperm in the epididymis. A biopsy of the testis taken at
      the time of exploration confirmed the FNAC findings. CONCLUSION: Clinical
      parameters are insufficient for diagnosing obstructive azoospermia. FNAC can
      accurately evaluate the testicular pathology and predict whether or not surgical
      exploration should be undertaken.

PMID- 16570681
TI  - HFE, hepcidin and ferroportin gene mutations are not present in Indian patients
      with primary haemochromatosis.
AB  - BACKGROUND: Primary haemochromatosis is characterized by iron overload in the
      body tissues. It is common in populations of northern European descent. In such
      populations, 85%-90% of patients with this disease have a C282Y mutation in the
      HFE gene. In India, the disease is uncommon and the genetic defects associated
      with it are unknown. We therefore looked for mutations in the HFE and other genes
      involved in iron metabolism in Indian patients with primary haemochromatosis.
      METHODS: Five patients (including a brother-sister pair) with primary
      haemochromatosis diagnosed on clinical, biochemical and histological findings
      were studied. Genomic DNA was analysed by sequencing for the presence of
      mutations in all the 6 exons of the HFE gene and for previously described
      mutations in genes encoding hepcidin antimicrobial peptide and ferroportin.
      RESULTS: No patient had the C282Y mutation. One had homozygous H63D mutation. No
      other mutation was found in any HFE exon. Two previously reported splice site
      mutations in the HFE gene (IVS3 + 1 G/T and IVS5+1 G/A) were not detected. Four
      of the 5 patients had an HFE splice site mutation (IVS2 + 4 T/C; homozygous 2,
      heterozygous 2); however, this change was as frequent in 29 healthy subjects
      (homozygous 9, heterozygous 7), and was present in only 1 of the sibling pair
      patients, indicating that this represented a polymorphism. No patient had any of
      the previously described mutations in the genes for hepcidin and ferroportin.
      CONCLUSION: Our patients with primary haemochromatosis lacked mutations in the
      HFE, hepcidin and ferroportin genes. Further genetic analysis may help identify
      novel mutations responsible for primary haemochromatosis in these patients.

PMID- 16570682
TI  - Role of EDTA chelation therapy in cardiovascular diseases.
AB  - Chelation therapy is a widely practised mode of treatment for atherosclerotic
      cardiovascular diseases all over the world. However, evidence for the utility of
      this therapy is limited and conflicting. We did a systematic review of the
      literature. The reference listings of the articles, obtained from a Pubmed search
      using relevant keywords, were searched for additional related articles. Most of
      the evidence supporting the use of EDTA chelation therapy is from case reports,
      small series or uncontrolled, open-label clinical trials. The published
      randomized controlled trials include few patients and their results are of
      limited value. Uncontrolled studies have reported symptomatic improvements but
      the few controlled trials suggest that these benefits are due to a placebo
      effect. The available data do not support the use of chelation in cardiovascular
      diseases. This therapy should be used only in the context of a research trial
      including patients who have failed to respond to conventional treatment.

PMID- 16570683
TI  - Medical applications of nanotechnology.
AB  - In the true spirit of interdisciplinary expansion of scientific knowledge,
      results from the applicability of nanotechnology in the fields of physical
      sciences and chemistry have now matured enough to extend into biology and
      medicine. The advances in nanotechnology in the past decade have offered novel
      opportunities for sensing clinically relevant markers, molecular dsease imaging
      and tools for therapeutic intervention, which have a potential to transform the
      field of medicine. We describe the currently available components of the nano
      toolbox, which are likely to be incorporated in clinical practice in the
      forseeable future. These include nanowires, cantilevers and nanopores for
      sensing, naoparticles and quantum dots for molecular imaging and nanoparticles
      for therapy. We also discuss the issue of toxicity of these nanomaterials and
      other limitations in the application of nanotechnology to medicine.

PMID- 16570685
TI  - Thick-walled gallbladder.

PMID- 16570684
TI  - Smallpox eradication: lessons learnt from a success story.

PMID- 16570687
TI  - Approval from abroad.

PMID- 16570686
TI  - Is the human immunodeficiency virus (HIV) epidemic slowing down in India?

PMID- 16570688
TI  - The Postgraduate Institute of Medicine.

PMID- 16570690
TI  - Stem cells: science and society.

PMID- 16570691
TI  - An unconventional teaching-learning tool for undergraduates.

PMID- 16570689
TI  - Unsolved mystery: uncompensated victims.

PMID- 16570692
TI  - Lymphoproliferative disorders in renal transplant recipients: a single-centre
      experience.

PMID- 16570693
TI  - The effect of probiotic bacteria on transepithelial calcium transport and calcium
      uptake in human intestinal-like Caco-2 cells.
AB  - While prebiotic substances have attracted considerable attention in terms of
      their stimulatory effect on intestinal calcium absorption, the potential
      influence of probiotic bacteria on calcium absorption has received little
      research emphasis. Therefore, the objective of this study was to investigate the
      effect of well-characterized probiotics (Lactobacillus salivarius (UCC 118) and
      Bifidobacterium infantis (UCC 35624)) on calcium uptake and transepithelial
      calcium transport in human intestinal-like, Caco-2, cells in culture. Cells were
      seeded onto permeable transport membranes and allowed to differentiate, over 16
      d, into intestinal-like cell monolayers. Monolayers (n=12-20/ treatment) were
      then exposed to E. coli UCC 118, UCC 35624 (10(7) cfu/ml) or no bacteria
      (control) for 6 or 24 h prior to calcium transport studies. Calcium transport was
      unaffected by exposure of Caco-2 cells to E. coli, UCC 118 or UCC 35624 for 6 or
      24 h. Calcium uptake into Caco-2 cell monolayers after 24 h was unaffected by UCC
      35624, but was significantly (P<0.05) or tended (P=0.079) to be increased by UCC
      118 and E. coli, respectively, relative to the control. In conclusion, the
      findings of this study which suggest that bacteria can enhance intestinal calcium
      uptake, if not calcium transport, highlights the need to undertake further
      studies in this, to date, vastly underinvestigated area.

PMID- 16570694
TI  - In vitro fermentation of mixed linkage glucooligosaccharides produced by
      Gluconobacter oxydans NCIMB 4943 by the human colonic microflora.
AB  - The aim of this study was to develop selectively fermented (prebiotic)
      carbohydrate molecules which would also result in the generation of butyric acid.
      Gluco-oligosaccharides produced by Gluconobacter oxydans NCIMB 4943 from various
      types of maltodextrins were evaluated for their fermentation by mixed cultures of
      human colonic microflora. The selectivity of growth of desirable bacteria
      (bifidobacteria, lactobacilli) was studied in stirred pH-controlled (6.8) batch
      cultures. Bacterial populations were enumerated using fluorescent in situ
      hybridization (FISH). Gluco-oligosaccharides resulted in significantly (P<0.05)
      increased numbers of bifidobacteria and lactobacilli within 24 hours.
      Bacteroides, clostridial and eubacterial populations were slightly decreased at
      48 h. There was very little difference in selectivity between the maltodextrin
      substrates and the products, although maltodextrin displayed a slightly less
      selective fermentation than the gluco-oligosaccharide products, also stimulating
      the growth of bacteroides, clostridia and eubacteria. Gluco-oligosaccharides,
      produced from G19 maltodextrin, resulted in the best prebiotic effect with the
      highest prebiotic index (PI) of 5.90 at 48 hours. Acetate, propionate and
      butyrate were all produced from gluco-oligosaccharides, derived from G19
      maltodextrin, at 48 hours but no lactate or formate were detected.

PMID- 16570695
TI  - In vitro three-stage continuous fermentation of gluco-oligosaccharides produced
      by Gluconobacter oxydans NCIMB 4943 by the human colonic microflora.
AB  - Gluco-oligosaccharides produced by Gluconobacter oxydans NCIMB 4943 from
      maltodextrin as the source, were evaluated for their fermentability by the human
      colonic microflora. The selectivity of growth of desirable bacteria in the human
      colon was studied in a three-stage continuous model of the human large intestine.
      Populations of bacteria, and their fluctuations as a response to the
      fermentation, were enumerated using fluorescent in situ hybridization (FISH). The
      gluco-oligosaccharides resulted in increases in numbers of bifidobacteria and the
      Lactobacillus/Enterococcus group in all 3 vessels of the system, representing the
      proximal, transverse and distal colonic areas. The prebiotic indices of the gluco
      oligosaccharides were 2.29, 4.23 and 2.74 in V1, V2 and V3 respectively.

PMID- 16570696
TI  - Chronic acid water feeding protects mice against lethal gut-derived sepsis due to
      Pseudomonas aeruginosa.
AB  - Acidified feeding formulas have been proposed as a method of controlling
      gastrointestinal colonization and nosocomial infection in critically ill
      patients. We examined possible mechanisms by which chronic acid water feeding
      might protect the host against lethal gut derived sepsis by assessing its effect
      on both local intestinal epithelial barrier function to bacteria as well as on
      local and systemic heat shock protein expression. Heat shock protein expression
      measured by immunoblot demonstrated that HSP25 was increased in the stomach,
      aorta and kidney of mice chronically fed acid water (8 weeks) compared to tap
      water fed controls. HSP72 expression was also increased in the aorta of mice
      drinking acid water. The protein content of cecum and its barrier function were
      enhanced in mice ingesting acidified water. The direct effect of an acid
      environment on intestinal epithelial barrier function was tested in cultured
      human intestinal epithelial cells. An acidified environment protected against
      bacterial mediated disruption of the intestinal epithelial barrier. Finally, the
      protective effect of chronic acid water feeding on gut-derived sepsis due to P.
      aeruginosa was tested in mice. Chronic acid water feeding protected mice from the
      lethal gut derived sepsis due to P. aeruginosa.

PMID- 16570697
TI  - Freezing at -800 degrees C distorts the DNA composition of bacterial communities
      in intestinal samples.
AB  - Terminal-restriction fragment length polymorphism (T-RFLP) was used to evaluate
      how to store intestinal specimens for bacterial community analysis. Bacterial
      communities are increasingly often described by means of DNA-based methods and it
      is common practice to store intestinal or faecal specimens either at -20 degrees
      C or -80 degrees C. In this study, samples of intestines from five different pigs
      were stored at -80 degrees C and -20 degrees C, respectively and a thawing and
      freezing procedure was carried out three times for each intestinal per pig per
      temperature. The cumulative sum of the T-RFLP peak heights (T-RF intensities)
      decreased as the temperature decreased. The composition of the bacterial
      community changed when stored at -80 degrees C compared to the samples stored at 
      20 degrees C. Thus it is recommended from this study that samples of intestinal
      content are stored at -20 degrees C before use for bacterial community analysis,
      instead of the current practice at -80 degrees C.

PMID- 16570698
TI  - Pandemic threat of avian influenza.

PMID- 16570699
TI  - Birth defects, the challenges ahead for Malaysia.

PMID- 16570700
TI  - Hepatitis B immunisation status among health care workers in two Kuala Lumpur
      hospitals.
AB  - Health care workers (HCW) are at higher risk of acquiring blood borne infections
      such as hepatitis B virus, hepatitis C virus and human immunodeficiency virus
      from patients. To minimise exposure, Universal Precautions Policy guidelines were
      introduced. This study looked into one of the aspects of hepatitis B prevention
      among HCW in the Malaysian context. The objective of this study was to assess
      hepatitis B vaccine coverage among HCW. A cross sectional study involving pre
      tested questionnaires was undertaken from February 2001 to August 2001. Hospital
      staff in Hospital Kuala Lumpur and Hospital Universiti Kebangsaan Malaysia as
      well as undergraduate students undergoing clinical attachments were randomly
      chosen. A total of 625 subjects were enrolled. Only 58.4% had taken a complete
      hepatitis B vaccination. However, 82.2% have taken at least one dose of the
      hepatitis B vaccine and were supposed to complete the schedule in due course. Not
      all HCW were protected against hepatitis B. Preventing hepatitis B in HCW should
      be one of the priorities of the hospital management as it is definitely cheaper
      than managing chronic hepatitis B cases.

PMID- 16570701
TI  - In-vitro activity of quinupristin/dalfopristin, levofloxacin and moxifloxacin
      against fusidic acid and rifampicin-resistant strains of methicillin-resistant
      Staphylococcus aureus (MRSA) from Malaysian hospitals.
AB  - The in-vitro susceptibility of quinupristin/dalfopristin, levofloxacin and
      moxifloxacin against methicillin-resistant Staphylococcus aureus (MRSA) strains,
      which are also resistant to fusidic acid and rifampicin were carried out to
      determine whether these antibiotics can be used as an alternative treatment for
      multiply resistant MRSA strains. The minimum inhibitory concentrations (MIC) of
      these antibiotics were determined by E-test. Quinupristin/dalfopristin had good
      activity (MIC90 = 1 mg/L) against these strains while most of the strains showed
      intermediate resistance to moxifloxacin with MIC90 = 2 mg/L). However, more than
      90% of these strains were resistant to levofloxacin with the MICs that ranged
      from 8 mg/L to 16 mg/L with the majority inhibited at 8 mg/L.

PMID- 16570702
TI  - Correlation between hypertension and income distribution among United Arab
      Emirates population.
AB  - To determine the correlation between hypertension and income distribution among
      United Arab Emirates (UAE) population. Case-control study matched for age, sex,
      nationality and education. The survey included 500 hypertensive adults aged 20-65
      years ascertained from Primay Health Care (PHC) Clinics along with a randomly
      selected sample of 500 control subjects from the community. Face-to-face
      interviews were done where data were gathered on socio-demographic-economic
      status (SES) and lifestyle habits. Hypertension was defined according to WHO
      criteria as having Systolic Blood Pressure (SBP) > or = 140 mm Hg and/or
      Diastolic Blood Pressure (DBP) > or = 90 mm Hg and/or being on antihypertensive
      treatment. The survey was carried out in urban and semi-urban PHC Clinics. A
      total of 818 subjects were included in this study from a sample of 1000; 409
      cases and 409 controls. There were 422 males and 396 females in this study, with
      255 UAE nationals and 438 expatriates. Hypertension was found to be significantly
      higher among the low income group (35.2% vs. 24.9% controls, p = 0.002; while
      mean SBP in the low income group was 130.2 +/- 17.6 vs. 128.0 +/- 17.4 controls,
      p = 0.022). Among males, smoking and alcohol consumption were higher among the
      group with low income level but only smoking showed significant difference (p
      value = 0.016). Activity level was higher among the low income groups. This study
      supports the importance of socio-economic factors as an income distribution
      effect on life-style habits and hypertension.

PMID- 16570703
TI  - Influence of co-morbidity in the interpretation of tuberculin skin reactivity in
      multi-ethnic adult patients with tuberculosis.
AB  - In the Malaysian setting of multi-ethnicity and high BCG coverage, interpretation
      of Tuberculin Skin Testing (TST) may be difficult. Between January 2001 and
      December 2003, a retrospective study on all adult patients with documented TST
      results treated for tuberculosis (TB) in chest clinics of two government
      hospitals was conducted to determine the reliability of TST and factors affecting
      its interpretation. One hundred and three patients [mean age (SD): 43 (17); male:
      67%] were eligible for data collection: 72% and 57% of patients had positive TST
      results based on cut-off points of 10mm and 15mm respectively. The only
      significant univariate association with TST results was the severity of co
      morbidity. A patient with co-morbidity score of 3 defined as those with any
      cancer, end-stage renal or liver disease, or HIV disease, was more likely to have
      a negative TST results [10mm cut-off point: Odd Ratio (95% CI) 6.6 (1.82 to
      24.35), p = 0.003; 15mm cut-off point: 4.8 (1.21 to 18.95), p = 0.012]. A TST
      reading of 10mm had a higher sensitivity than 15mm as the cut-off point in
      diagnosing TB infection. Considering all possible confounding factors like
      ethnicity, prior BCG vaccination and TB burden in the population, severity of co
      morbidity remains strongly predictive of a negative TST. Caution should be
      exercised in interpreting TST in these patients.

PMID- 16570704
TI  - Perceived skill and utilisation of information technology in medical education
      among final year medical students, Universiti Putra Malaysia.
AB  - The objective of this survey was to obtain a self-reported assessment of the use
      of information technology (IT) by final year medical students. Two hundred and
      sixty five students responded to a questionnaire survey. 81.5% of students
      considered their computer skills adequate, while 87.9% had access to computers
      outside the campus. Most students reported adequate skills at word processing, e
      mailing and surfing the Internet. Fifty three percent of students spent three
      hours or more each week on the computer. While students indicated a general
      willingness to access Internet-based materials, further steps need to be taken to
      increase the use of this method of instruction.

PMID- 16570705
TI  - Subclinical eating disorder, polycystic ovary syndrome- is there any connection
      between these two conditions through leptin- a twin study.
AB  - The genetic property of subclinical eating behaviour (SEB) and the link between
      SEB and polycystic ovary syndrome (PCOS) has been studied before but the role of
      leptin within this connection has never been investigated. The objective of this
      study was 1). to study the genetic property of SEB. 2). To find a link between
      leptin, SEB and PCOS. One hundred and fifty four (77 pairs) female-female Iranian
      twins including 96 MZ individuals (48 pairs) and 58 DZ individuals (29 pairs)
      participated in the study. Clinical, biochemical and ultrasound tools were used
      to diagnose polycystic ovary syndrome. BITE questionnaire was filled out for
      subjects. Eight percent of subjects were diagnosed for subclinical eating
      disorder. No significant difference was found between intraclass correlation of
      MZ and DZ (z = 0.57, P = 0.569). Serum leptin level correlated significantly with
      bulimia score (P < 0.007). The mean (+/-SD) value for bulimia score was found to
      be higher among PCOS(positive) subjects (3.27 +/- 5.51) in comparison with
      PCOS(negative) subjects (2.06 +/- 4.48) (P < 0.001). The genetic property of
      subclinical eating disorder was not confirmed as shared environment might have
      played a major role in likeliness of DZ twins as well as MZ. Leptin is linked
      with both subclinical eating disorder and PCOS.

PMID- 16570706
TI  - Rapid and cost-effective antenatal diagnosis of haemoglobin Bart's hydrops
      foetalis syndrome using a duplex-polymerase chain reaction.
AB  - Haemoglobin Bart's hydrops foetalis syndrome (--SEA/--SEA) is not compatible with
      life and contributes to a majority of the hydropic foetuses in the Malaysian
      Chinese alpha-thalassaemia carriers who possess the 2-alpha-gene deletion in cis
      (--SEA/alphaalpha). A duplex-PCR which simultaneously amplifies a normal 136 bp
      sequence between the psialpha-alpha2-globin genes and a 730 bp Southeast Asian
      deletion-specific sequence (--SEA) between the psialpha2-theta1-globin genes was
      established. The duplex-PCR which detects the --SEA deletion in both chromosomes
      serves as a rapid and cost-effective confirmatory test in the antenatal diagnosis
      of Haemoglobin Bart's hydrops foetalis syndrome in Malaysia. In addition, the
      duplex-PCR is simple to perform as both the normal and deletion-specific alpha
      globin gene sequences are amplified in the same PCR reaction.

PMID- 16570707
TI  - Use of complementary medicine amongst hypertensive patients in a public primary
      care clinic in Ipoh.
AB  - The use and reasons for use of Complementary Medicine (CM) amongst hypertensive
      patients attending the Hypertension/ Diabetes/ Asthma Clinic in Greentown Health
      Clinic, Ipoh was assessed. One hundred and twenty patients were selected by
      systematic random sampling (1:5) over a 2-week period commencing 26/04/04. Data
      was obtained from interviews, questionnaires and medical records. Twenty seven
      percent were on CM. Most commonly used CM was herbal medicine. Majority of those
      using CM for BP control were Malays. The Chinese and Indians were using CM mainly
      for other health problems. Ninety six percent were using both CM and conventional
      therapy concurrently. Therefore doctors should enquire about CM usage during
      patient assessment to prevent possible drug interactions.

PMID- 16570708
TI  - Audit of birth defects in 34,109 deliveries in a tertiary referral center.
AB  - The objective of the study is to determine the proportion and different types of
      birth defects among the children born in Hospital Kuala Lumpur. A cross-sectional
      study was conducted for a period of 18 months where all consecutively born
      infants, dead or alive were included. There were total of 34,109 births recorded
      during this period. The proportion of birth defects in Hospital Kuala Lumpur was
      3.1% (n = 1056). The commonest involved were the hematology system, (157.7 per
      10,000 births), the central nervous system, genitourinary system and chromosomal
      anomalies. The proportion was significantly higher in males and in the Chinese (p
      < 0.001). The commonest abnormalities are Glucose 6 Phosphate Deficiency
      (157.7/10000), Down's syndrome (12.6/10000), thalassaemia (8.8/10000), cleft lip
      and/or palate (7.6/10000) and anencephaly (7.3/10000). Neural tube defect is
      common and ranked second after G6PD deficiency. There is a need for a birth
      defect registry to assess the extent of the problem in Malaysia.

PMID- 16570709
TI  - Ultrasound measurement of corporeal (penile) length in newborns.
AB  - In the initial clinical examination of a child with ambiguous genitalia an
      accurate measurement of the corporeal length is needed. Most often the corporeal
      length is measured with a ruler from the symphysis pubis to the tip of the glans
      of a stretched penis. More recently, ultrasound has been successfully used to
      measure corporeal length. This study aimed to (i) establish normal values for
      corporeal length in normal male newborns using ultrasound measurement, (ii)
      compare these measurements to stretched corporeal measurements, (iii) compare the
      corporeal length of newborns of different races, and (iv) determine the
      relationship between corporeal length and birth weight, birth length and head
      circumference. This was a prospective study of 141 newborns. Ultrasound imaging
      was done in an oblique parasagittal plane such that the corpus could be included
      in a single image and measured, Stretched corporeal length was measured with the
      penis stretched alongside a wooden spatula and the length from the pubic bone to
      the tip of the glans was marked on the spatula and measured. By ultrasound
      measurement the mean corporeal length of the normal newborn was 3.18 +/- 0.56cm.
      There was no significant difference in the mean corporeal length when determined
      by ultrasound and by stretched corporeal measurement. There was no significant
      difference in the mean corporeal length of the different races when the length
      was determined by either ultrasound or stretched corporeal measurement. There was
      a positive correlation between ultrasound length and birth weight and birth
      length. However, there was no correlation between ultrasound length and head
      circumference. There was no significant correlation between the stretched length
      and either birth weight, birth length or head circumference.

PMID- 16570710
TI  - Audit of hypertension in general practice.
AB  - An audit of hypertension management was done in October 2004 in nine general
      practice (GP) clinics. Two structure, ten process and two outcome indicators were
      assessed. Results showed that targets were achieved in only four indicators,
      i.e., weight recording (89%), BP monitoring (85.8%), follow-up interval not
      exceeding 6 months (87.9%) and mean diastolic BP (73.9%). The other indicators
      (hypertension registry, reminder mechanisms for defaulters, recording of smoking,
      height, fundoscopy, monitoring of lipid profile, blood sugar, ECG, renal function
      and achievement of target mean systolic pressure) showed adequacy percentages
      varying from 22.1 to 68.7. Out of the 1260 patients assessed, 743 (59%) achieved
      a mean BP < or = 140/90 (or < or = 130/80 mmHg with diabetes mellitus / renal
      insufficiency) in the last 3 recorded readings. There was a vast difference
      between individual clinics. Reasons for not achieving targets were discussed and
      remedial measures for implementation were recommended.

PMID- 16570711
TI  - Epidermal cyst of submandibular gland.
AB  - The differential diagnosis of a cystic lesion in the submandibular area can be
      difficult. We report a case of epidermal cyst of submandibular gland which is
      relatively rare compared to the commoner epidermoid cyst.

PMID- 16570712
TI  - Sino-nasal hemangiopericytoma--a rare tumor.
AB  - Hemangiopericytoma is a very rare angiogenic tumor. In the nasal cavity, it can
      be considered malignant. It occurs in various parts of the body but those in the
      nasal cavity account for only 5% of total cases. Less than 200 cases have been
      reported worldwide involving the nose and paranasal sinuses. Due to its rarity a
      proper line of management has not been established to tackle this tumour. This
      article highlights two cases of hemangiopericytoma (HPC), one in an adult and the
      other in a child, presenting as an intranasal mass.

PMID- 16570713
TI  - Large vestibular aqueduct syndrome.
AB  - Large Vestibular Aqueduct Syndrome is a congenital malformation of the temporal
      bone characterised by early onset of sensorineural hearing loss and vestibular
      disturbance. Familial large vestibular aqueduct syndrome suggests autosomal
      recessive or X-linked inheritance and accounts for non-syndromic sensorineural
      hearing loss in these patients.

PMID- 16570714
TI  - Successful pregnancy in untreated limited Wegener's granulomatosis.
AB  - A thirty four year old female presented with upper and lower respiratory symptoms
      in the third trimester of pregnancy. After the delivery of a healthy baby, the
      symptoms progressed to involve multiple organ systems and eventually a diagnosis
      of limited Wegener's Granulomatosis (Carrington-Liebow syndrome) was made. The
      extremely rare combination of WG and pregnancy, especially the onset of disease
      in late pregnancy is discussed. The successful outcome of pregnancy even without
      treatment of WG is the highlight of the case.

PMID- 16570715
TI  - Abdominal aorta and inferior vena cava thromboses in advanced stage of malignant
      fibrous histiocytoma.
AB  - Asymptomatic simultaneous thrombosis of abdominal aorta and inferior vena cava is
      a rare complication in advanced malignancy. We described an incidental finding of
      this clinical entity in our patient who presented with advance stage of malignant
      fibrous hystiocytoma of soft tissue and pathological fracture. The radiological
      evaluation with spiral computed tomography scan of abdominal aorta and inferior
      vena cava are presented and the subsequent management highlighted.

PMID- 16570716
TI  - Tracheal stent in the treatment of tracheal stenosis.
AB  - The use of airway stents for the treatment of benign airway stenosis is
      increasingly advocated. However, the long-term safety and efficiency of these
      devices has not been established. We present a case of tracheal stenosis. which
      persisted despite open surgical and laser correction. The patient required
      tracheal stent insertion and is currently well with no respiratory difficulty.
      The use of metallic or silicon intraluminal stent remains appropriate in cases in
      which there is defined and relative short-term end point of treatment.

PMID- 16570717
TI  - Accelerated diabetic retinopathy in pregnancy--a real and present danger.
AB  - A 36 year-old Malay lady with diabetes mellitus in pregnancy and poorly
      controlled hypertension developed rapid progression of diabetic retinopathy from
      no retinopathy to florid proliferative retinopathy over three months in her right
      eye. She had subsequent loss of vision due to vitreous haemorrhage in the peri
      partum period. She had good final visual acuity with quiescent retinopathy
      following pars planar vitrectomy. A similar course was avoided in the left eye by
      timely pan retinal photocoagulation.

PMID- 16570718
TI  - The pudendal thigh fasciocutaneous flap for vaginal atresia reconstruction.
AB  - Vaginal defects can either be congenital or acquired due to tumor or trauma. The
      reconstructions are aimed in producing a good physical and functional result with
      the least donor site morbidity. The pudendal thigh flap is a sensate
      fasciocutaneous flap based on the terminal branch of the superficial perineal
      artery, the continuation of the internal pudendal artery. Although various flaps
      have been described for vaginal reconstruction, the pudendal thigh flap offers a
      very attractive alternative.

PMID- 16570719
TI  - A rare case of middle mediastinal thymoma mimicking left lower lobe lung tumor.

PMID- 16570720
TI  - Chronic rupture of the extensor apparatus of the knee joint.
AB  - Chronic ruptures of the extensor mechanism of the knee are uncommon injuries, and
      previously reported literature assumes the presence of an intact patella for
      repair. We present a case of chronic rupture following patellectomy done twelve
      years previously. The defect in the extensor apparatus was extensive (18cm), and
      this was bridged using a large fascia lata graft from the opposite thigh, with
      reasonably successful results.

PMID- 16570721
TI  - Neurocysticercosis an uncommon intra-cerebral infection in Malaysia.
AB  - Neurocysticercosis, infection of the central nervous system (CNS) by larvae of
      the pork tapeworm Taenia solium, is the commonest neuroparasitic infection in
      humans. However in countries as in Malaysia it poses a diagnostic problem as the
      disease in not seen amongst the local population; however with the arrival of
      immigrant workers, a number of cases have recently been diagnosed. There were 3
      cases of neurocysticercosis reported in our centre over the last 5 years.

PMID- 16570722
TI  - Peginterferon alfa-2b and ribavirin in thalassaemia/chronic hepatitis C virus-co
      infected non-responder to standard interferon-based.
AB  - We describe a patient with HbE-beta thalassaemia and chronic hepatitis C virus
      infection (genotype 1a) who was treated successfully with peginterferon alfa-2b
      and ribavirin, following failure to respond to standard interferon and ribavirin
      therapy. She had sustained virological response for nearly 24 months after
      completing peginterferon alfa-2b and ribavirin therapy. Transfusion requirements
      were significantly increased during combination therapy due to ribavirin-induced
      haemolysis. The adverse effects of interferon were well tolerated. Combination
      therapy with peginterferon alfa-2b and ribavirin maybe a feasible treatment
      option for a subset of thalassaemia/HCV infected non-responders to standard
      interferon-based therapy.

PMID- 16570723
TI  - The dilemma of a lateral pharyngeal mass causing stridor in a neonate.
AB  - Neonatal stridor resulting from intrinsic or extrinsic aberration in the upper
      respiratory tract often poses not only a diagnostic problem, but also a difficult
      airway and a dilemma as to the necessity / timing of surgical intervention. A 45
      day old female child with increasing stridor since birth was managed by emergency
      intubation and CT scan followed by excision biopsy of the cystic left sided
      parapharyngeal mass via a transcervical approach. On histopathology, the excised
      specimen was reported as cystic salivary choristoma.

PMID- 16570725
TI  - Hearing impairment in the elderly.
AB  - Hearing impairment is one of the most important health problems of the elderly
      above 60. Very often it leads to verbal communication difficulty and without
      treatment it can cause serious psychological and social complications such as
      depression and social isolation. Prebyscusis remains a leading cause of
      sensorineural deafness in the elderly. Elderly patient must be encouraged to seek
      proper hearing assessment if they face hearing difficulty. Active screening by
      health care workers and patient self-evaluation by answering a simple list of
      screening questions are possible for early detection and treatment of hearing
      loss in the elderly. Although hearing loss in the elderly may not have a cure,
      early rehabilitation helps to restore better quality of life if the problem is
      detected early.

PMID- 16570724
TI  - Migration of a foreign body in the maxillary sinus illustrating natural
      mucociliary action.
AB  - We present a case of a foreign body which migrated to the maxillary ostia by
      mucociliary action from its initial location on the floor of the maxillary sinus
      where it was traumatically introduced. This report illustrates that a powerful
      mechanism of mucociliary action can cause relatively heavy objects within the
      maxillary sinus to migrate naturally to the sinus ostia against gravitational
      force.

PMID- 16570726
TI  - The causes of stalling fertility transitions.
AB  - An examination of fertility trends in countries with multiple DHS surveys found
      that in the 1990s fertility stalled in midtransition in seven countries:
      Bangladesh, Colombia, Dominican Republic, Ghana, Kenya, Peru, and Turkey. In each
      of these countries fertility was high (more than six births per woman) in the
      1950s and declined to fewer than five births per woman in the early or mid-1990s,
      before stalling. The level of stalling varied from 4.7 births per woman in Kenya
      to 2.5 births per woman in Turkey. An analysis of trends in the determinants of
      fertility revealed a systematic pattern of leveling off or near leveling in a
      number of determinants, including contraceptive use, the demand for
      contraception, and number of wanted births. The stalling countries did not
      experience significant increases in unwanted births or in the unmet need for
      contraception during the late 1990s, and program effort scores improved slightly,
      except in the Dominican Republic. These findings suggest no major deterioration
      in contraceptive access during the stall, but levels of unmet need and unwanted
      births are relatively high, and improvements in access to family planning methods
      would, therefore, be desirable. No significant link was found between the
      presence of a stall and trends in socioeconomic development, but at the onset of
      the stall the level of fertility was low relative to the level of development in
      all but one of the stalling countries.

PMID- 16570727
TI  - Quality of care in China: scaling up a pilot project into a national reform
      program.
AB  - China's family planning program ranks as history's most intensive effort to
      control national population growth. Although advocates for global population
      control have lauded China's effort to limit births as afundamental part of its
      sustainable development goals, the country's population policy has also generated
      much international criticism. As China enters the new millennium, a long-overdue
      reform of its approach to implementing its family planning program has begun to
      refocus the program on clients' needs, informed choice of contraceptives, and
      better-quality services. Originally inspired by the 1994 International Conference
      on Population and Development held in Cairo, the reform program began as a pilot
      project among six counties and has now become a blueprint for reorienting the
      national family planning program. This article reviews the process by which a
      small, innovative pilot project was scaled up into a national reform effort and
      the key lessons learned about scaling up sensitive but necessary innovation in a
      difficult political environment.

PMID- 16570728
TI  - Farming with your hoe in a sack: condom attitudes, access, and use in rural
      Tanzania.
AB  - This study examines condom knowledge, attitudes, access, and practices in rural
      Mwanza, Tanzania. From 1999-2002, six researchers carried out participant
      observation in nine villagesfor a total of 158 person-weeks. Many villagers
      perceived condoms negatively for multiple reasons, for example, the method's
      association with infection or promiscuity, reduced male sexual pleasure, and
      cultural understandings of meaningful sex. Men controlled the terms of sexual
      encounters and reported that they would use condoms only with risky partners, but
      few perceived their partners as such. Use of condoms appeared to be very low,
      primarily as a result of limited demand, although barriers to access also
      existed. These qualitative findings contrast with inconsistent survey reports of
      relatively high condom use in the same population. Intervention efforts should
      address the tradeoff between possible short- and long-term consequences of condom
      use, particularly for men, for example, reduced pleasure versus reduced HIV risk.
      If possible, surveys should assess the validity of reported condom use through
      comparison with other data, including qualitative findings and distribution/sales
      records.

PMID- 16570729
TI  - Levels and trends in cesarean birth in the developing world.
AB  - Evidence suggests that cesarean birth rates are high and increasing in some
      developing countries. The objectives of this study are to compile the best
      current estimate of cesarean birth rates for developing countries, to estimate
      regional rates, and to document trends nationally and by urban/rural residence
      where data permit. A database of cesarean birth rates was compiled representing
      90 percent of births in the developing world, resulting in an estimated cesarean
      birth rate for the developing world of 12 percent, with regional rates ranging
      from 3 to 26 percent. Data representing 45 percent of births in the developing
      world show that a majority of countries experienced increases in cesarean birth
      rates during the 1990s, except in sub-Saharan African countries, where little if
      any change occurred. Cesarean birth rates must be monitored routinely to call
      attention to rapidly changing practices. These data can, in turn, trigger
      investigation into the appropriateness of the rate in a given context.

PMID- 16570730
TI  - The quality of hospital-based antenatal care in Istanbul.
AB  - The aim of this study was to gather comprehensive data from three hospitals in
      Istanbul, Turkey, in order to gain in-depth understanding of the quality of
      antenatal care in this setting. The Bruce-Jain framework for quality of care was
      adapted for use in evaluating antenatal care. Methods included examination of
      hospital records, in-depth interviews, exit questionnaires, and structured
      observations. The study revealed deficiencies in the quality of antenatal care
      being delivered at the study hospitals in all six elements of the quality-of-care
      framework. The technical content of visits varied greatly among the hospitals,
      and an overuse of technology was accompanied by neglect of some essential
      components of antenatal care. Although at the private hospital some problems with
      the technical content of care were identified, client satisfaction was higher
      there, where the care included good interpersonal relations, information
      provision, and continuity. Providers at all three hospitals felt constrained by
      heavy patient loads and a lack of resources. Multifaceted approaches are needed
      to improve the quality of antenatal care in this setting.

PMID- 16570731
TI  - Cameroon 2004: results from the demographic and health survey.

PMID- 16570732
TI  - Morocco 2003-04: results from the Population and Family Health Survey.

PMID- 16570733
TI  - Statins in primary prevention: uncertainty in women, elderly.

PMID- 16570734
TI  - Out-of-hospital cardiac arrest and use of automated external defibrillators.

PMID- 16570735
TI  - Childhood and adolescent sports-related overuse injuries.
AB  - Youth sports participation carries an inherent risk of injury, including overuse
      injuries. Little leaguer's shoulder, a stress fracture of the proximal humerus
      that presents as lateral shoulder pain, usually is self-limited. Little leaguer's
      elbow is a medial stress injury; treatment consists of complete rest from
      throwing for four to six weeks followed by rehabilitation and a gradual throwing
      program. Spondylolysis is a stress fracture of the pars interarticularis.
      Diagnostic modalities include plain film radiography, bone scan, computed
      tomography, single photon emission computed tomography, and magnetic resonance
      imaging. Treatment usually is conservative. Spondylolisthesis is the forward or
      anterior displacement of one vertebral body over another and may be related to a
      history of spondylolysis. Diagnosis is made with plain film radiography and
      graded according to the amount of displacement. Osgood-Schlatter disease presents
      as anterior knee pain localized to the tibial tubercle. Diagnosis is made
      clinically, and most patients respond to conservative measures. Calcaneal
      apophysitis (or Sever's disease) is a common cause of heel pain in young
      athletes, presenting as pain in the posterior aspect of the calcaneus.

PMID- 16570736
TI  - Preventing postpartum hemorrhage: managing the third stage of labor.
AB  - Postpartum hemorrhage is a significant cause of maternal morbidity and mortality.
      Most postpartum hemorrhages are caused by uterine atony and occur in the
      immediate postpartum period. Expectant or physiologic management of the third
      stage of labor has been compared with active management in several studies.
      Active management involves administration of uterotonic medication after the
      delivery of the baby, early cord clamping and cutting, and controlled traction of
      the umbilical cord while awaiting placental separation and delivery. Good
      evidence shows that active management of the third stage of labor provides a
      better balance of benefits and harms and should be practiced routinely to
      decrease the risk of postpartum hemorrhage. Oxytocin, ergot alkaloids, and
      prostaglandins have been compared, as have timing and route of administration of
      these uterotonic medications. Oxytocin is the uterotonic agent of choice; it can
      be administered as 10 units intramuscularly or as 20 units diluted in 500 mL
      normal saline as an intravenous bolus, and can safely and effectively be given to
      the mother with the delivery of the baby or after the delivery of the placenta.

PMID- 16570738
TI  - Information from your family doctor. Driving and dementia: what you should know.

PMID- 16570737
TI  - Older adult drivers with cognitive impairment.
AB  - As the number of drivers with cognitive impairment increases, family physicians
      are more likely to become involved in decisions about cessation of driving
      privileges in older patients. Physicians who care for cognitively impaired older
      adults should routinely ask about driving status. In patients who continue to
      drive, physicians should assess pertinent cognitive domains, determine the
      severity and etiology of the dementia, and screen for risky driving behaviors.
      Cognitive impairment detected by office-based tests may indicate that the patient
      is at risk of a motor vehicle crash. Referral for performance-based road testing
      may further clarify risk and assist in making driving recommendations. Physicians
      should assist families in the difficult process of driving cessation, including
      providing information about Web sites and other resources and clarifying the
      appropriate state regulations. Some states require reporting of specific medical
      conditions to their departments of motor vehicles.

PMID- 16570739
TI  - Retinoblastoma.
AB  - Retinoblastoma, a neuroblastic tumor, is the most common primary intraocular
      malignancy of childhood. Patients usually present with leukokoria (white reflex
      or white pupil), detected in primary care. The mean age at diagnosis is 12 months
      for bilateral tumors and 24 months for unilateral tumors. If untreated, almost
      all patients die of intracranial extension and disseminated disease within two
      years. However, new diagnostic and treatment methods allow for a high cure rate
      (93 percent five-year survival in the United States), therefore it is important
      that primary care physicians recognize the manifestations of this malignancy.
      Diagnosis is primarily by history and complete ophthalmic examination, with
      studies including ultrasonography of the eye and imaging of the orbits and brain.
      Treatment modalities include laser thermotherapy, cryotherapy, radioactive
      plaques, external beam radiotherapy, chemotherapy, and enucleation. Prospective
      parents with a family history of retinoblastoma should be referred for genetic
      counseling. Office evaluation for a red reflex in children should be performed
      until three years of age. If leukokoria is observed, the patient should be
      examined by an ophthalmologist within one week.

PMID- 16570740
TI  - The patient with excessive worry.
AB  - Worry is a normal response to uncertainty. Education, empathetic support,
      reassurance, and passage of time usually ameliorate ordinary worries. However,
      these common-sense strategies for dealing with transient worries often prove
      ineffective for patients with excessive worry, many of whom meet the criteria for
      disorders in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed.
      Evidence-based treatments for such disorders can assist family physicians in
      management of persistent worry as a self-perpetuating habit across diagnostic
      categories. Antidepressants and cognitive behavioral therapy are effective
      treatments for various disorders characterized by excessive worry. Cognitive
      behavioral strategies that may be adapted to primary care contacts include
      education about the worry process, repeated challenge of cognitive distortions
      and beliefs that underpin worry, behavioral exposure assignments (e.g., scheduled
      worry periods, worry journals), and learning mindfulness meditation.

PMID- 16570741
TI  - Information from your family doctor. What you should know about worrying too
      much.

PMID- 16570742
TI  - Red streaks on the leg. Lymphangitis.

PMID- 16570743
TI  - Amlodipine/atorvastatin (Caduet) for preventing heart disease.

PMID- 16570744
TI  - Improving dental public health services through advancement of a workforce
      agenda.

PMID- 16570745
TI  - An assessment of the dental public health infrastructure in the United States.
AB  - OBJECTIVES: The National Institute of Dental and Craniofacial Research
      commissioned an assessment of the dental public health infrastructure in the
      United States as a first step toward ensuring its adequacy. This study examined
      several elements of the U.S. dental public health infrastructure in government,
      education, workforce, and regulatory issues, focused primarily at the state
      level. METHODS: Data were drawn from a wide range of sources, including original
      surveys, analysis of existing databases, and compilation of publicly available
      information. RESULTS: In 2002, 72.5% of states had a full-time dental director
      and 65% of state dental programs had total budgets of 1 million dollars or less.
      Among U.S. dental schools, 68% had a dental public health academic unit. Twelve
      and a half percent of dental schools and 64.3% of dental hygiene programs had no
      faculty member with a public health degree. Among schools of public health, 15%
      offered a graduate degree in a dental public health concentration area, and 60%
      had no faculty member with a dental or dental hygiene degree. There were 141
      active diplomates of the American Board of Dental Public Health as of February
      2001; 15% worked for state, county, or local governments. In May 2003, there were
      640 U.S. members of the American Association of Public Health Dentistry with few
      members in most states. In 2002, 544 American Dental Association members reported
      their specialty as Dental Public Health, which ranged from 0 in five states to 41
      in California. Just two states had a public health dentist on their dental
      licensing boards. CONCLUSIONS: Findings suggest the U.S. dental public health
      workforce is small, most state programs have scant funding, the field has minimal
      presence in academia, and dental public health has little role in the regulation
      of dentistry and dental hygiene. Successful efforts to enhance the many aspects
      of the U.S. dental public health infrastructure will require substantial
      collaboration among many diverse partners.

PMID- 16570746
TI  - Effect of different diagnostic thresholds on dental caries calibration.
AB  - OBJECTIVES: (a) To analyze the intra- and inter-examiner reproducibility
      (reliability) of a calibration trial, at different diagnostic thresholds of
      dental caries; (b) to verify the accuracy (benchmark validity) though sensitivity
      (S), specificity (SP), positive (PPV) and negative predictive (NPV) values.
      PARTICIPANTS: A group of dental examiners (n=11), who had previous experience in
      epidemiological surveys and six to seven-year-old children. Children were
      selected according to the dmft and dental caries activity. METHODS: Theoretical
      and clinical training and calibration exercises were arranged for a total of 28
      hours. WHO criteria including the active initial lesions (IL) were used. MAIN
      OUTCOME MEASURES: WHO and WHO+IL diagnostic thresholds according to tooth and
      dental surface. RESULTS: Excellent mean results of intra and inter-examiner Kappa
      values were found for both diagnostic thresholds, according to tooth and surface,
      during the calibration phase. The most relevant errors were related to IL
      diagnosis and to the first permanent molars. When assessed against a benchmark
      examiner, moderate to high validity values were observed (0.71-1.00), with some
      loss mainly for sensitivity and positive predictive value, when including IL.
      CONCLUSION: It was possible and feasible to use the proposed methodology of this
      study in epidemiological surveys, even with the inclusion of IL. However, further
      examiner calibration studies are still needed in order to improve and establish a
      methodology of calibration with this new diagnostic threshold.

PMID- 16570747
TI  - Associations of ethnicity/race and socioeconomic status with early childhood
      caries patterns.
AB  - OBJECTIVES: The purpose of this project was to evaluate ethnicity/race, household
      income and caregiver education level as predictors of (1) any early childhood
      caries, and (2) each of four proposed patterns of primary dentition caries.
      METHODS: Between February 1994 and September 1995, five examiners visually
      examined Arizona pre-school children ages 5-59 months old. Self-reported
      demographic information including family income, caregiver education level and
      ethnicity/race were obtained at the time of examination. Multivariate analyses
      were conducted to assess the association of income, education and ethnicity/race
      with a child having any caries and with each of the proposed caries patterns seen
      in 3850 examinations. RESULTS: Income and education were inversely associated
      with: (1) any early childhood caries, and (2) the maxillary incisor caries
      pattern. A positive association between these caries patterns and minority
      ethnicity/race status was also identified. Three additional caries intraoral
      patterns demonstrated more varied associations with socioeconomic status (SES),
      ethnicity/race and income and education. CONCLUSIONS: This study supports the
      association of both ethnicity/race and social status with any early childhood
      caries. The patterns of caries were each found to be associated with specific and
      different socioeconomic-demographic indicators. The practical importance of these
      findings is that global measurement of ECC, without regard to specific caries
      pattern, leads to the potential for substantial non-differential
      misclassification of disease. The consequence of this is the potential for
      important ECC-SES-ethnicity/race associations to be masked. This, in turn,
      decreases the ability of surveys and investigations to accurately identify sub
      groups of the population at greatest risk of developing ECC.

PMID- 16570748
TI  - Assessment of the relationship between neighborhood characteristics and dental
      caries severity among low-income African-Americans: a multilevel approach.
AB  - OBJECTIVES: To assess the relationship between neighborhood effects and the
      severity of dental caries among low-income African-Americans. METHODS: A
      multistage probability sample of African-American families living in the poorest
      39 census tracts in Detroit was drawn. During 2002-03, cross-sectional data of a
      cohort that includes 1021 caregivers were collected in the first of three waves
      of interviews and examinations. Multilevel analyses focused on 27 neighborhood
      clusters and involved a combination of individual (Level-1) and neighborhood
      (Level-2) data including census and geocoded (address matching to census
      geographic areas) information. RESULTS: There is significant variation in the
      severity of caries between low-income neighborhood clusters. Caries severity
      decreases with a higher number of churches, while it increases with a higher
      number of grocery stores in the clusters after accounting for individual
      characteristics. Only 14% of the inter-individual variability in caries was
      explained by classical individual risk factors for this condition. CONCLUSION:
      Neighborhoods contribute something unique to caregivers' oral health, beyond
      socioeconomic position and individual risk factors. Multilevel interventions are
      necessary to reduce disparities among African-Americans and churches may offer a
      promising venue from which to conduct them.

PMID- 16570749
TI  - Decision-making process for treatment of mandibular fractures among minority
      groups.
AB  - OBJECTIVES: While patients' preferences for medical care are widely studied, only
      a small number of studies have looked at the decision-making process for dental
      treatment of mandibular fracture. This study examines the decision-making process
      for treatment of mandibular fractures among minority groups. Study participants
      were asked to consider Maxillomandibular Fixation (MMF--a non-surgical approach
      of wiring the teeth for 4-8 weeks) or Rigid Internal Fixation (RIF--surgical
      placement of bone plate). METHODS: A qualitative study of patients receiving care
      at an inner-city hospital for either 3rd molar extraction under general
      anesthesia or a mandibular fracture were recruited to participate in an hour-long
      focus group to discuss their preferences. The 3rd molar group was selected as a
      comparison group exemplifying experience with oral surgery and recovery from
      general anesthesia. RESULTS: Seven decision-making factors affecting choice of
      treatment were discussed by both jaw fracture and 3rd molar groups, including:
      side effects, effectiveness of each treatment, trusting doctor's recommendation,
      what to expect from each procedure, use of pictures from previous case studies,
      surgery location of scar/incision, and size of scar. Rigid Internal Fixation
      (RIF) participants discussed a different set of concerns compared to
      Maxillomandibular Fixation (MMF) participants. CONCLUSIONS: Regardless of gender,
      the treatment of choice for both 3rd molar and jaw fracture participants was the
      non-surgical method of wiring of the teeth for 4-8 weeks. The Phase II part of
      this study will systematically examine patient preferences among a larger sample
      of 3rd molar and jaw fracture patients by incorporating the patient-reported
      concerns about treatment of jaw fracture found in this inductive,
      phenomenological study.

PMID- 16570750
TI  - Opinions of South Carolina dental students toward tobacco use interventions.
AB  - OBJECTIVES: Tobacco use accounts for 75 percent of oral cancer deaths in the
      United States. One objective of Healthy People 2010 is to increase the percentage
      of dentists who provide smoking cessation counseling. However, studies of
      dentists have shown that the majority feel inadequately prepared to do so. The
      objective of this study was to determine the opinions of dental students at the
      Medical University of South Carolina (MUSC) regarding the provision of tobacco
      use interventions for patients. METHODS: In 2002, 163 students were administered
      a written questionnaire which included questions about tobacco use interventions
      (response rate=80 percent). Opinion items were analyzed using factor analysis,
      Fisher's Exact Test, and ANOVA (a < or = 0.025). RESULTS: While 89 percent of
      students agreed that dentists should be trained to provide tobacco cessation
      education, only 39 percent thought that they themselves were adequately trained.
      Students' opinions toward the role and training of dentists in providing tobacco
      use interventions differed by academic year. Only 14.1 percent of dental students
      were quite or very confident in their ability to help patients to stop smoking.
      CONCLUSIONS: This study indicates that although MUSC dental students support
      tobacco cessation training for dentists, the majority responded that they are not
      adequately trained and are not comfortable providing tobacco cessation education
      to patients. A comprehensive tobacco prevention and cessation program is
      indicated for the objective of Healthy People 2010 to be met.

PMID- 16570751
TI  - The relationship between cardiovascular xerogenic medication intake and the
      incidence of crown/root restorations.
AB  - OBJECTIVES: This retrospective, longitudinal cohort study quantified the strength
      of the association between xerogenic cardiovascular medication use and dental
      restorations, using the latter as a proxy measure for dental caries experience.
      METHODS: Study data were collected from 11 years of electronic clinical/pharmacy
      records in two large dental group practices associated with managed care
      organizations (MCO). Records were extracted for all members who were at least 55
      years old at the end of the 11 year window, and had at least 48 months of
      concurrent dental, medical, and pharmacy coverage. The authors identified 4448
      individuals whose only xerogenic medication exposure was to drugs treating a
      cardiovascular condition. This group was compared to a group not taking any
      medications (n=1183), and a group taking medications with no known xerostomic
      side effect (n=5622). Poisson regression compared restoration incidence and mean
      restoration rates among the three groups. RESULTS: MCO members taking
      cardiovascular or nonxerogenic medications had higher restoration incidence and
      mean restoration rates than individuals taking no medications. A small difference
      in mean restoration rate between the non-xerogenic medication group and the
      cardiovascular drug group was observed; no significant difference in restoration
      incidence was seen between these two groups. CONCLUSIONS: This study provides
      objective quantification of cardiovascular medication's long-term effects on
      increased restorations in older adults. When grouped under a single category
      labeled "cardiovascular", drugs with effects targeting the cardiovascular system
      did not appear to unequivocally lead to higher restorative experiences.

PMID- 16570752
TI  - The cost-effectiveness of large amalgam and crown restorations over a 10-year
      period.
AB  - OBJECTIVE: To assist clinical decision making for an individual patient or on a
      community level, this study was done to determine the differences in costs and
      effectiveness of large amalgams and crowns over 5 and 10 years when catastrophic
      subsequent treatment (root canal therapy or extraction) was the outcome. METHODS:
      Administrative data for patients seen at the University of Iowa, College of
      Dentistry for 1735 large amalgam and crown restorations in 1987 or 1988 were
      used. Annual costs and effectiveness values were calculated. Costs of initial
      treatment (large amalgam or crown), and future treatments were determined,
      averaged and discounted. The effectiveness measure was defined as the number of
      years a tooth remained in a state free of catastrophic subsequent treatment.
      Years free of catastrophic treatment were averaged, and discounted. The years
      free of catastrophic treatment accounted for individuals who dropped out or
      withdrew from the study. RESULTS: Teeth with crowns had higher effectiveness
      values at a much higher cost than teeth restored with large amalgams. The cost of
      an addition year free of catastrophic treatment for crowns was 1088.41 dollars at
      5 years and 500.10 dollars at 10 years. Teeth in women had more favorable cost
      effectiveness ratios than those in men, and teeth in the maxillary arch had more
      favorable cost-effectiveness ratios than teeth in the mandibular arch.
      CONCLUSIONS: Neither the large amalgam or crown restoration had both the lowest
      cost and the highest effectiveness. The higher incremental cost-effectiveness
      ratio for crowns should be considered when making treatment decisions between
      large amalgam and crown restorations.

PMID- 16570753
TI  - Are oral health status and care associated with anxiety and depression? A study
      of Portuguese health science students.
AB  - The relationship between oral health and anxiety/depression were assessed in a
      cross-sectional study conducted in 388 Portuguese students from the Health
      Sciences (age: 21 +/- 3 years, 75% women). Oral health included prevalence of
      reported tooth pain/gum bleeding, dentist attendance, and dentifrice and dental
      floss use. Anxiety and depression were assessed by the Hospital Anxiety and
      Depression Scale. Subjects with anxiety or depression had a higher frequency of
      perceived gum bleeding and reported a higher dentist attendance than normal
      subjects. On multivariate analysis, anxiety was significantly and independently
      related to perceived toothache (OR = 2.90, 95% CI: 1.25-6.72) and dentist
      attendance (OR = 2.15, 95% CI: 1.18 - 3.91) whereas depression was associated
      with perceived gum bleeding (OR = 4.96, 95% CI: 1.68 - 14.59), and no differences
      were found regarding teeth brushing or dental flossing. The author concludes that
      anxiety and depression are related to perceived toothache and gum bleeding, but
      this association cannot be explained by decreased dental care.

PMID- 16570754
TI  - Demographic factors associated with dental utilization among community dwelling
      elderly in the United States, 1997.
AB  - OBJECTIVES: The purpose of this study was to characterize dental service
      utilization in 1997 by community dwelling Medicare beneficiaries. METHODS: The
      Medicare Current Beneficiary Survey, or MCBS, is a continuous annual series of
      nationally representative surveys of Medicare beneficiaries. Univariate
      comparisons were made between dependent variables (dental utilization and types
      of dental services) by each of the independent variables (age group, gender,
      race, income, education, population density, marital status and U.S. Census
      Bureau regions using weighted proportions to test for independence between
      dependent and independent variables. RESULTS: Overall, an estimated 41% of the
      population had a dental visit. Although utilization declined with aging, 24% of
      those 85 and older visited a dentist. CONCLUSIONS: This descriptive study
      provides important information about dental utilization and services in the
      American elderly population. Younger, high income, white or educated elderly
      Americans had higher dental utilization.

PMID- 16570755
TI  - Response to "Comments on the proposed pediatric oral health therapist".

PMID- 16570757
TI  - Status of adolescent health in India.

PMID- 16570756
TI  - Prediabetes--to treat or not to treat.

PMID- 16570758
TI  - Prevalence of diabetes in various habitats of West Bengal, India.
AB  - The epidemiological profile data were collected for diabetes mellitus from the
      people living in three habitats (rural, industrial and urban) having considerable
      difference in their lifestyle and socio-economic status. Every 5th (occasionally
      4th or 6th) member from each habitat was sampled; no restriction regarding age
      was kept during screening; OGTT (oral glucose tolerence test) was performed 2
      hours after 75 g glucose, in those whose FBS (fasting blood sugar) was >90 mg/dl.
      Diagnosis of diabetes mellitus was ascertained, if the FBS was >120 mg/dl and/ or
      postglucose value was >200mg/dl. The per cent prevalence (among all aged people)
      of diabetes mellitus in rural, industrial and urban habitats were found to be:
      1.66 +/- 0.58 (male 1.99 +/- 0.88, female 1.3 +/- 0.75); 3.00 +/- 0.74 (male 3.17
      +/- 1.04, female 2.80 +/- 1.04) and 4.8 +/- 0.98 (male 5.31 +/- 1.43, female 4.27
      +/- 1.32) respectively.

PMID- 16570759
TI  - Risk factor analysis in ischaemic stroke: a hospital-based study.
AB  - Stroke represents a major health burden in our country. Ischaemic stroke has got
      several risk factors associated with increased chance of atherosclerosis. A small
      hospital-based study was done to look into the risk factors associated with
      ischaemic stroke. Forty patients with CT-confirmed cerebral infarction were taken
      for the study and detailed history and clinical findings were obtained.
      Investigations like complete haemogram, fasting blood glucose, urea, creatinine,
      lipid profile, serum Lp(a), homocysteine, fibrinogen, ECG, chest x-ray,
      echocardiography, MRI/MRA where indicated, were done to identify the risk factors
      as well. Results indicated that hypertension was the most prevalent (87.5%) risk
      factor followed by ischaemic heart disease (35%) and diabetes. Dyslipidaemia was
      also found in a significant number of cases, mostly elevated LDL, low HDL and
      elevated Lp(a). Fibrinogen and homocysteine were of less significance.

PMID- 16570760
TI  - Detection of cancer cervix by estimation of sialic acid.
AB  - The study was undertaken to determine the sialic acid concentration of cervical
      tissue and serum of women with healthy and unhealthy cervix. The sialic acid
      value in local tissue of cervix and in serum showed slight elevation in benign
      inflammatory lesions, moderate elevation was found in severe dysplasia and
      preinvasive carcinoma and marked elevation in invasive carcinoma cervix. The
      values, both in the serum and in the cervical tissue, increased gradually with
      the advancement of grading of frank malignancy. The elevation of sialic acid in
      the serum was slow to start with but persisted for a longer period, wereas the
      concentration in local tissue was found to be increasing with the pathological
      process.

PMID- 16570761
TI  - Epidemiological aspects of prediabetes--review of the current data.
AB  - The term 'prediabetes' has been used to describe the condition in which blood
      glucose levels are higher than normal but not yet diabetic and includes the two
      abnormalities, impaired glucose tolerance (IGT) and impaired fasting glucose
      (IFG). Subsequent to the American Diabetes Associaton (ADA) recommendation to
      adjust downward the normal fasting glucose level from 110 to 100 mg/dl, the
      prevalence of IFG has increased by 2 to 4 fold. The demonstration by recent
      randomised controlled trials that type 2 diabetes mellitus is preventable has
      raised hope for the possibility of reducing cardiovascular morbidity and
      mortality associated with diabetes. Interventions like lifestyle modification and
      pharmacological therapy are recommended in individuals with prediabetes to
      achieve the goal of prevention of diabetes in high -risk population.

PMID- 16570762
TI  - Pathophysiology of prediabetes.
AB  - Type 2 diabetic patients pass through a phase of impaired glucose tolerence
      and/or impaired fasting glucose known as 'prediabetic state'. Prediabetic state
      form a part of syndrome X, other components being obesity, hypertension,
      dyslipidaemia, hyperinsulinaemia and insulin resistance. The pathophysiology of
      prediabetes is similar to type 2 diabetes mellitus, two basic defects are insulin
      resistance and early beta cell failure. In prediabetes, the rapid oscillations of
      insulin secretion are lost and amplitude of large pulses are decreased. When
      insulin is delivered in a pulsatile fashion that mimics the normal rapid
      oscillation, its hypoglycaemic effects are greater. In prediabetes, the glycaemic
      excursions after each meal are high and early insulin responses to meals tend to
      be lower than normal but the second phase of insulin secretion is delayed and
      prolonged.

PMID- 16570763
TI  - Nutrition in prediabetes.
AB  - Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are
      forerunners of type 2 diabetes mellitus (DM) and are now recognised as
      prediabetes states. Cardiovascular disease (CVD) is associated with these
      conditions and there are many studies such as the Da Quin IGT and DM study;
      Finnish Diabetes Prevention Study(DPS); The Diabetes Prevention Program(DPP)
      which have clearly shown the efficacy and supremacy of diet intervention in
      controlling progression of the prediabetes state to type 2 DM. Weight reduction,
      increasing physical activity and restricting not only total calories but also
      deriving them from more healthy sources by reducing the total intake of fat,
      changing n-6 PUFA to n-3 PUFA, increasing the intake of fibre rich carbohydrates
      and the use of antioxidants have not only long-term health benefits but also can
      be a very useful cost-effective tool to overcome the burden of type 2 DM in our
      country. Prevention of type 2 DM is not a dream but a reality and this can be
      achieved from a path through our kitchen. Faulty nutrition seems to be the main
      culprit in this wide-spread epidemic of diabetes and nutritional therapy in
      prediabetes state appears to be the only option in our hands.

PMID- 16570764
TI  - Exercise in prediabetes.
AB  - Exercise as a therapeutic modality in the management of type 2 diabetes is well
      established. However, exercise has emerged as an important tool to prevent, or at
      least, to delay the onset of type 2 diabetes. This has been borne out by a few
      recent clinical trials. Exercise improves insulin sensitivity besides having
      beneficial effects on many cardiovascular risk factors. A sedentary adult at high
      risk for developing diabetes may benefit from at least 30 minutes of daily
      moderate-intensity exercise.

PMID- 16570765
TI  - Drug therapy in prediabetes.
AB  - Patients with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT)
      have been designated by American Diabetes Association (ADA, 2004) as having
      'prediabetes', which indicates the higher risk of developing the disease in these
      patients. Prediabetes is important to recognise because of at least 2 major
      implications: increased risk for future diabetes and for atherosclerotic
      cardiovascular diseases. Pharmacotherapy in prediabetes should therefore be
      directed at preventing or, at least, delaying the onset of the disease as well as
      reducing the morbidity and mortality from atherosclerotic complications. Several
      drugs having different mechanisms of action, such as metformin, glitazones,
      acarbose, orlistat, nateglinide, glicazide, angiotensin-converting enzymes,
      angiotensin receptor blockers have been found to be effective in prediabetes to
      improve the glycaemic status, though they are still not recommended by any
      professional organisation.

PMID- 16570766
TI  - Prevention of type 2 diabetes in the prediabetic population.
AB  - Prevention of diabetes has been tried by several groups with varying degree of
      success. Prediabetic population are the ideal target for the purpose. In this
      study, prediabetic subjects are selected from the high-risk groups, like those
      having obesity, family history of diabetes, past history of gestational diabetes,
      hypertension, dyslipidaemia; and are included in the study when their fasting
      plasma glucose was found to be below 110 mg/dl and 2 hours postglucose (75g)
      plasma glucose remained between 110 and 200 mg/dl. After giving advice for
      lifestyle changes to all for a period of 3 months, those who had their blood
      glucose values in the impaird glucose tolerance (IGT) range were given either
      metformin, rosiglitazone or acarbose, the rest continued with diet and exercise
      only. Total follow-up period was 3 years. All groups maintained blood sugar in
      the euglycaemic range till the end of the 3-year period.

PMID- 16570768
TI  - Enabling medical professionals to respond effectively and with sensitivity to the
      needs of adolescents.
AB  - Adolescence is a period when important changes occur in an individual's life. It
      is a period of both risk to health and well-being, and of opportunity to set the
      stage for healthy adulthood. Most adolescents are healthy, but a small (and in
      some places not so small) proportion of them face health (including both physical
      and psychological) problems as well as social problems. Many individuals and
      institutions have important contributions to make in ensuring the health of
      adolescents. Medical professionals have crucial contributions to make--both as
      service providers and as community-change agents. Studies from many places show
      that adolescents value medical professionals as credible sources of help, and
      reach out to them for health information and services, albeit in small numbers.
      However, studies from many parts of the world suggest that medical professionals
      are unable and/or unwilling to respond to the needs of adolescents effectively
      and with sensitivity. There is growing recognition of the public-health benefits
      of strengthening the technical as well as the inter-personal competencies of
      medical professionals, and of helping them clarify their attitudes so that they
      could deal with adolescents with understanding and respect. Initiatives in this
      area are under way in many countries. WHO strongly supports these capacity
      building initiatives, and urges that orientation and training programmes be
      followed up with ongoing support to enable medical professionals to perform to
      the best of their abilities. WHO also stresses the importance of informing and
      engaging families and communities to support the provision of health information
      and services to young people.

PMID- 16570767
TI  - Pathogenesis and management of diabetic foot--a review.
AB  - In the present article, the pathophysiology, evaluation and management guidelines
      of diabetic foot infections are reviewed with a view to reducing the medical
      morbidity, psychological distress and financial costs.

PMID- 16570769
TI  - Adolescent health screening questionnaire.
AB  - Adolescent screening questionnaire is a set of questions made on determinants of
      adolescent health and used to screen adolescents exposed to health risk
      environment to offer preventive and promotional health care . Most evidence based
      questionnaire (GAPS) was developed by American Medical Association. Subsequently
      American Academy of Pediatrics (AAP) and Bright Future (BF) developed
      questionnaire. All of them were developed to serve American and Western society
      needs. Format of Adolescent Preventive Services (FAPS) questionnaire was prepared
      by Adolescent Health Clinic of Calcutta Medical College to suit Indian
      adolescents, having a different cultural background, with technical support from
      WHO. National consultations on this questionnaire was supported by WHO and GOI.
      It was field tested and its validity and reliability were assessed among
      adolescents of six school students. Use of this tool helps identification of
      adolescents exposed to high-risk environments and use of necessary early
      intervention to prevent morbidity and mortality in adolescents. The available
      software version of FAPS can be used in the computer class to screen all school
      adolescents regularly.

PMID- 16570770
TI  - Adolescent vaccination.
AB  - Indian Academy of Pediatrics (IAP) has taken an important step towards adolescent
      vaccination. In the present article, the author has briefly described the needs
      for adolescent immunisation along with the IAP vaccination schedule for
      adolescents, in details.

PMID- 16570771
TI  - Adolescent onset of adult metabolic diseases.
AB  - There has been a significant rise in many adult diseases linked with obesity like
      insulin resistance, type 2 diabetes, hypertension, coronary artery disease,
      hyperlipidaemia and stroke. These diseases have been shown to have their origin
      in adolescence, specially in children who are getting bulkier relative to
      themselves. Thus it is important that an individual child is monitored with
      regular weight and/or serial BMI measurements. Creating a healthy environment
      specially in schools which include increased physical activity would probably be
      the best intervention strategy to check undue weight gain in adolescents.

PMID- 16570772
TI  - Eye health and adolescence.
AB  - Complete development of eyes occurs between 8 and 11 years, though longitudinal
      growth of axial length may occur up to 13 years (approximately). Except a few,
      most of the eye diseases affecting adolescence age group are similar to adult
      type. Diseases like myopia, keratoconus, vernal keratoconjunctivitis, juvenile
      diabetic retinopathy and injuries to eye are exclusively diseases of adolescence
      that are commonly encountered. Psychologically, impact of eye disease on
      adolescent mind may be profound, thinking they might lose their eyesight. Early
      detection of diseases, prevention of injuries, health education and frequent eye
      check-up are essential.

PMID- 16570773
TI  - Puberty and pubertal disorders.
AB  - The authors have focussed in this article on normal physical growth during
      puberty and events during adolescence with a brief mention of pubertal disorders.

PMID- 16570774
TI  - Personality development.

PMID- 16570775
TI  - Laparoscopic repair for femoral hernia.

PMID- 16570776
TI  - Hospital management, administration and medical profession.

PMID- 16570777
TI  - [New discoveries on sudden infant death. Pacifiers protect, "co-sleeping" and
      nicotine (also patch/chewing gum) increase the risk].

PMID- 16570778
TI  - [Most adverse events in orthopedics, as shown by the Patient's Insurance. The
      injury panorama and care utilization in this patient group surveyed].

PMID- 16570779
TI  - [The civil war in Liberia hard particularly to women. Rapes, devastated homes,
      divided families have left deep wounds].

PMID- 16570780
TI  - [In the "Sodertalje model" the municipality and the county work together. Joint
      support benefits the psychiatric reform patients].

PMID- 16570781
TI  - [Children with earache--nothing for the physician?].

PMID- 16570782
TI  - [Shall narrow-minded scientific view direct the choice of treatment of depression
      and anxiety?].

PMID- 16570783
TI  - [More than 1 out of 100 will have myocardial infarction and stroke because of
      enalapril--effect of drug package inserts?].

PMID- 16570784
TI  - [Misleading advice on cholesterol reduction].

PMID- 16570785
TI  - [Good reasons for physicians to compete for administrative leadership].

PMID- 16570786
TI  - [B-vitamins and homocysteine--the current debate is necessary!].

PMID- 16570787
TI  - [A disastrous "reform"].

PMID- 16570788
TI  - [One thousand cataract extractions daily in a monastery].

PMID- 16570789
TI  - [General situation of the toxicity researches on Senecio].
AB  - This article summarized the toxic components, toxication faeature and mechanism
      and clinical poisoning reports of Senecio spp. The distribution of major toxic
      components pyrrolizidine alkaloids (PAs) in Chinese medicinal herbs and the
      application of Senecio spp. in China were also recapitulated. The proposals for
      the application and development of Senecio spp. were put forward.

PMID- 16570790
TI  - [The review of Amomum villosum in Xishuangbanna].
AB  - The researches on quality evaluation, chemical composition, pharmacological
      actions and plantation of Amomum villosum in Xishuangbanna was reviewed. The
      further research point were proposed.

PMID- 16570791
TI  - [Advances of studies on dropping pills].
AB  - From the characteristic, prepare the craft, quality control, bioavailability and
      clinical curative effect,etc. To do the summary to the modern research of
      dropping pill, analyse and is thought to dropping pill that has wide development
      prospects.

PMID- 16570792
TI  - [Effects of light and plant growth regulators on growth of normal and hairy root
      of Lycium barbarum in vitro].
AB  - OBJECTIVE: To study effects of the cycle of light and exogenous plant growth
      regulators on growth of normal root and hairy root of Lycium barbarum and
      establish a long-term system of in vitro culture of L. barbarum roots. METHOD:
      Using normal roots from aseptic seedlings and hairy roots originated from
      Agrobacterium rhizogenes A4-mediated genetic transformation of L. barbarum, the
      growth of root segments was examined after 20 days of culture under different
      culture conditions. RESULT AND CONCLUSION: When cultured on the MS medium with
      different plant growth regulators (IAA, IBA, NAA), normal root segments of L.
      barbarum could elongate and branch, and the addition of 1 mg x L(-1) IBA into the
      medium was the most suitable for long-term in vitro culture of L. barbarum root.
      When cultured on MS medium without hormone, light promoted the elongation and
      lateral root formation of type II hairy root, but not of type I hairy root. Among
      three tested hormones, IAA at low concentration was the best for growth of type I
      hairy root, while 1 mg x L(-1) IBA was the most suitable for growth of type II
      hairy root. With the increase of hormone level added into MS medium, callusing
      frequencies of type I, II hairy roots were increased, at the same time, the
      formation of lateral root from hairy root or callus was inhibited.

PMID- 16570793
TI  - [Study on resource and varieties of Guoshangye].
AB  - OBJECTIVE: To investigate the varieties, resoures and identification
      authentication of Guoshangye used in Tuja and Miao's folk. METHOD: Through field
      investigations and comparing the collected specimens and literatures, the
      classification and identification of the species were studied. RESULT AND
      CONCLUSION: Origin of Guoshangye plant was from Pholidota yunnanensis,
      Bulbophyllum andersonii, B. odoratissimum, B. kamgtimgemse, ect. their
      morphological characters were identified. Due to limited resource of Guoshangye,
      the development and protection should be paid more attention.

PMID- 16570794
TI  - [Karyotypes analysis of Ferula fukanensis].
AB  - OBJECTIVE: Study on the karyotypes analysis of Ferula fukanensis. METHOD: The
      young roots were treated with 0.000 2 mol x L(1) 8-Hydroxyquinoline for 3 h,
      carnoy's for 3 h, 1 mol x L(-1) HCl in 5 min,carbol fuchsin coloration for 2 min
      and the treated roots were utilizied to make the plate for observation. RESULT:
      The fukanensis is diploid. The chromosome number of somatic cells was 2n = 22.
      The karyotype formula is 2n = 2x = 20 = 16m + 4sm. The 4th and 10th are
      submetacentric, and the others are metacentric. CONCLUSION: The karyotype of F.
      fukanensis belongs to "2A" type of stebbins', and it is a primitive species.

PMID- 16570795
TI  - [Determination of epicatechin in Rhizoma Fagopyri dibotoryis by HPLC-ECD].
AB  - OBJECTIVE: To establish a quantitative method of determination of epicatechin in
      Rhizoma fagopyri dibotoryis by HPLC-electrochemical detection. METHOD: The sample
      was separated on a column of Diamonsil C18 (4.6 mm x 250 mm, 5 microm) which was
      eluted with methanol-0.1 mol x L(-1) phosphate buffer (1:3, pH 2.5), the flow
      rate was 1.0 mL x min(-1), the column temperature was 35 degrees C, the reference
      electrode was ISAAC (in-situ silver/silver chloride), the work electrode was
      glassy carbon, the applied potential was + 600 mV. RESULT: The linear range of
      epicatechin was 0.004 875-1.56 microg, r = 0.999 9. The average recovery was
      100.7% with RSD 1.9% (n = 5). The content of epicatechin was different in nine
      samples purchased. CONCLUSION: The method is good reproducible and can be used to
      determine epicatechin in Rhizoma fagopyri dibotoryis.

PMID- 16570796
TI  - [Determination of salidroside and p-tyrosol in Hongjingtian for
      injection(freezing-dry) by SPE-HPLC].
AB  - OBJECTIVE: To assay salidroside and p-tyrosol in Hongjingtian for injection
      (freezing-dry). METHOD: Samples were purified by Sep-Pak C18 column and
      salidroside and p-tyrosol were determined by HPLC with Irregular-H C18 (4.6 mm x
      250 mm, 5 microm), and eluted with a mobile phase of methanol-acenitonitrile 
      0.06% phosphate (10: 10:80). The flow rate was 1.0 mL x min(-1), the detection
      wavelength was set at 275 nm and the column temperature was maintained at 30
      degrees C. RESULT: The calibration curves were linear in the range of 2.24-22.4
      microg for salidroside (0.999 7) and 0.856-8.56 microg for p-tyrosol (0.999 6),
      the average recovery was 101.3%, 99.8% respectively. CONCLUSION: The method is
      convenient, rapid, accurate and reliable.

PMID- 16570797
TI  - [Determination of aristolochic acid A in Guanxinsuhe preparations by RP-HPLC].
AB  - OBJECTIVE: To establish a determination method of aristolochic acid A in
      Guanxisuhe preparations by RP-HPLC. METHOD: The instrument used was Hewlett
      Packard 1100 HPLC with a Alltech C18 column (4.6 mm x 250 mm, 5 microm). The
      mobile phase was methanol-water-acetic acid (68: 32:1) and the flow rate was 1.0
      mL x min(-1). The UV detection wavelength was 390 nm and the column temperature
      was at 35 degrees C. The extracted solvent for the preparations was methanol
      solution contained 10% formic acid. RESULT: The calibration curve was linear (r =
      0.999 9) within the range of 0.119-1.89 microg for aristolochic acid A. The
      average recovery 99.0%, RSD 0.63%. CONCLUSION: The method with good linear
      relationship was convenient, quick, accurate, and suitable for the quality
      control of the aristolochic acid A in Guanxinsuhe and other traditional Chinese
      medicines containing aristolochic acid A.

PMID- 16570798
TI  - [Studies on chemical constituents of the brown alga Dictyopteris divaricata].
AB  - OBJECTIVE: To investigate the chemical constituents of the brown alga D.
      divaricata, and to test cytotoxicities of the purified compounds. METHOD:
      Compounds were isolated by normal phase silica gel, Sephadex LH-20 chromatography
      and reverse phase HPLC techniques. Their structures were elucidated by
      spectroscopic methods including IR, MS and NMR. Cytotoxicities were tested by MTT
      method. RESULT: Eight compounds were isolated from ethanolic extract of the brown
      alga D. divaricata and their structures were identified as (-)-torreyol (I),
      4beta, 5alpha-dihydroxycubenol (II), 3-farnesyl-p-hydroxybenzioc acid (III),
      chromazonarol (IV), fucosterol (V), phenyl acetylamine (VI), 4-hydroxybenzoic
      acid (VII) and n-hexadecanoic acid (VIII). CONCLUSION: Compound II and IV were
      obtained from this alga for the first time. The others were isolated from the
      Dictyotaceae algae for the first time. All compounds were inactive (IC50 > 10
      microg x mL(-1)) against human tumor cell lines KB, Bel-7402, PC-3M, Ketr 3 and
      MCF-7.

PMID- 16570800
TI  - [Chemical constituents from roots of Ficus hirta].
AB  - OBJECTIVE: To study the chemical constituents from the roots of Ficus hirta.
      METHOD: Compounds were isolated by chromatographic techniques on silica gel and
      HP-20 resin columns. Their structures were elucidated by chemical and
      spectroscopic methods. RESULT: Ten compounds were identified as beta-sitosterol
      (1), stigmasterol (2), psoralene (3), 3beta-hydroxy-stigmast-5-en-7-one (4), 5
      hydroxy-4', 6, 7, 8-tetramethoxy flavone (5), 4', 5, 6, 7, 8-pentamethoxy flavone
      (6), 4', 5, 7-trihydroxy-flavone (7), 3beta-acetoxy-beta-amyrin (8), 3beta
      acetoxy-alpha-amyrin (9) and hesperidin (10). CONCLUSION: The compounds 4, 5, 6
      were obtained from this genus for the first time, and all the compounds were
      obtained from this plant for the first time.

PMID- 16570799
TI  - [Studies on chemical constituents of Patrinia villosa].
AB  - OBJECTIVE: To investigate the chemical constituents of Patrinia villosa. METHOD:
      The chemical constituents were isolated by silica gel column chromatography and
      semi-preparative high-performance liquid chromatography, and identified by
      physicochemical properties and spectral analysis (MS, 1H-NMR and 13C-NMR).
      RESULT: Seven compounds were isolated from ethyl acetate and n-butanol extract
      and identified as: 5-hydroxyl-7, 3', 4'-trimethoxy flavone (I), 5-hydroxyl-7, 4'
      dimethoxy flavone (II), luteolin (III), quercetin (IV), isoorientin (V),
      isovitexin (VI) and 8-C glucosylprunetin (VII). CONCLUSION: Compounds I , II,
      III, V, VI and VIII were obtained from the plant of genus Patrinia for the first
      time, compound IV was separated from P. villosa for the first time.

PMID- 16570801
TI  - [Chemical constituents from root of Lasianthus acuminatissimus I].
AB  - OBJECTIVE: To investigate the chemical constituents from the root of Lasianthus
      acuminatissimus of Rubiaceae. METHOD: Normal, reverse phase silica gel,
      macroporous resin column and HPLC chromatography were used for isolation.
      Spectroscopic methods (13C-NMR, 1H-NMR, DEPT, EI-MS) were used for
      identification. RESULT: Six compounds were isolated and elucidated as
      isoscopletin(I), isoscopletin-6-O-beta-D-glucopyranoside (II), beta configuration
      of Mudanoside-A (Ill), asperuloside (IV), (-)-pinoresinol 4-O-beta-D
      glucopyranoside (V), daucosterol (VI). CONCLUSION: These compounds were obtained
      from this plant for the first time.

PMID- 16570802
TI  - [Study on reflux esophagitis treated by Tongjiang granule].
AB  - OBJECTIVE: To study the mechanism of Tongjiang granule on treating GERD. METHOD:
      The rats in the model group received steel wire ring-cardiamyopexy. A steel wire
      ring was fixed firmly on cardia. The rats in the control group underwent the
      cardia-plasty plus pylori ligation plus stomach-empty intestine Roux-en-Y
      anastomosis. The rats were divided into six groups after operations at random,
      which were fed up respectively with Tongjiang granule of different dosage and
      perpulsid. No treatment groups were taken as control. RESULT: The experiment
      showed that Tongjiang granule could lighten or cure RE in the pathology, decrease
      the hydrochloric acid in gastric juice, in the meantime, increase the motilin in
      the animal blood. This study indicated that the effect of Tongjiang granule group
      from experimental research was better than that of the control group (perpulsid).
      CONCLUSION: The effects of Tongjiang granule on treating GERD can be achieved by
      decreasing the hydrochloric acid in gastric juice, increasing the motilin in
      blood and promoting the gastric impetus in the animal experiment.

PMID- 16570804
TI  - [Effect of ursolic acid on caspase-3 and PARP expression of human MCF-7 cells].
AB  - OBJECTIVE: To study the effect of ursolic acid (UA), apentacyclic triterpene
      acid, on MCF-7 cell apoptosis, and probable mechanism involved by detecting the
      expressions of caspase-3 and poly ADP-ribose polymerase(PARP) at protein level.
      METHOD: MCF-7 cells were cultured with different concentrations of UA. Growth
      inhibition of UA on MCF-7 cells was evaluated by MTT assay. Cell cycle and sub-G1
      peak were performed by FCM. Morphologic changes of UA-treated cells were observed
      by light microscope. Apoptotic cells with condensed or fragmented nuclei were
      visualized by Ho 33258 staining by a fluorescence microscope (EX: U. V.). The
      protein expression of caspase-3 and PARP was analyzed by immunofluorescence cell
      staining (SABC-Cy3). RESULT: 24 hours after UA treatment, inhibition of MCF-7
      cell growth was concentration-dependent. The IC50 value for UA was (22.6 +/- 3.0)
      micromo x L(-1). Cell cycle anaysis by FCM showed that 50 micromol x L(-1) of UA
      arrested MCF-7 cell cycle at G0 - G1 phase. Morphological changes of MCF-7 Cells
      exhibited many of the hallmark features of apoptosis, including chromatin clumps
      and aggregation and DNA fragmentation. UA increased caspase-3 protein expression.
      CONCLUSION: The results suggest that UA evokes MCF-7 cell apoptosis is
      correlation with the up-regulation of caspase-3. Our study indicated that UA
      might be a potential Chinese medical component for breast neoplasm.

PMID- 16570803
TI  - [The preotective effects of total glycosides Rubus parviflolius on cerebral
      ischemic in rat].
AB  - OBJECTIVE: To observe the protective effects of total glycosides Rubus
      parviflolius (TGRP) on local cerebral ischemic. METHOD: The local cerebral
      ischemia in rat was made by middle cerebral artery occlusion(MACO). The
      infraction weight was determined by TTC stain. SOD, MDA, GSH and apoptotis were
      determined with different method respectively. RESULT: TGRP 20, 10 mg x kg(-1) ig
      markedly improved the abnormal nervous symptoms, incredsed the SOD, GSH activity
      and reduced contentes of MDA in brain of MACO rat, TGRP 20 mg x kg(-1) ig
      significantly decreased the numbers of apoptotic cells in ischemic cortex.
      CONCLUSION: TGRP has protective effects against cerebral infraction, and its
      mechanism may be related to anti-apoptotis and free radical.

PMID- 16570806
TI  - [Studies on antitumor effects of podophyllotoxin nanoliposome].
AB  - OBJECTIVE: To compare the antitumor effects of the podophyllotoxin nanoliposome
      and the suspensions of podophyllotoxin in bearing-tumor mice. METHOD: The
      experimental mice were inoculated by suspension liquid of tumor cell in axillary
      region near the forelimb, 0.2 mL each. The mice had been randomly divided into 8
      groups 24 h latter. The podophyllotoxin nanoliposome, suspension liquid of the
      podophyllotoxin, CX or NS was given to each group respectively. Except CX was
      given by celiac injection once, the other groups were injected every 4 days for
      three times. The mice were killed by hauling necks on the twelfth day after
      treatment, the tumor was weighed and the inhibitory rate was calculated. RESULT:
      When the dosage of podophyllotoxin nanoliposome and the suspensions of
      podophyllotoxin reached 5.0 mg x kg(-1), the rate of inhibiting tumor were 52.37%
      and 38.25% to the H22 liver cancer of mice respectively. CONCLUSION:
      Podophyllotoxin nanoliposome and the suspensions of podophyllotoxin have the
      effect in anti-liver cancer. And podophyllotoxin nanoliposome have stronger
      inhibitory rate compared with suspension liquid of the podophyllotoxin in same
      dose.

PMID- 16570805
TI  - [Effects of traditional tibetan medicine, Fructus Lonicerae microphyllae on
      phagecytosis and cytokines production of murine macrophages].
AB  - OBJECTIVE: To explore the effects of traditional Tibetan medicine, Fructus
      Lonicerae microphyllae (FLM) on phagecytosis and cytokines production of murine
      macrophages. METHOD: The phagecytosis of murine macrophages was analyzed by
      neutral red phagecytosis assay. The activities of IL-1 and TNF-alpha were
      measured by biological methods. The mRNA of TNF-alpha and INF-gamma expressed by
      macrophages was detected by RT-PCR. RESULT: The phagecytosis of murine
      macrophages was significantly enhanced by FLM at a concentration from 1 microg x
      mL(-1) to 100 microg x mL(-1) and the secretions of IL-1, and TNF-alpha from
      macrophages were markedly induced by FLM. Meanwhile, FLM also increased the
      expression of TNF-alpha mRNA and INF-gamma mRHA from macrophages in vitro.
      CONCLUSION: FLM could promote phagecytosis and cytokines production of murine
      macrophages.

PMID- 16570807
TI  - [Effect of Gleditsia sinensis stings on growth inhibition and expression of PCNA
      and p53 in mice bearing uterine cervical carcinoma (U14)].
AB  - OBJECTIVE: To study the antitumor effect of the stings of Gleditsia sinensis on
      mice bearing uterine cervical carcinoma (U14) and the expression of PCNA
      (proliferating cell nuclear antigen) and p53. METHOD: The effect of the ethanolic
      extract of G. sinensis stings on the inhibition rate of solid tumor and the life
      span of ascites tumor were calculated by the animal tumor model experiment in
      vivo. The positive cell numbers of PCNA and mutant p53 protein were measured by
      immunohistochemical SP method. RESULT: As compared with the control group, the
      ethanolic extract of G. sinensis stings (250, 500 and 1 000 mg x kg(-1) body
      weight, p.o.) and CTX (25 mg kg(-1) body weight, i.p.) administration
      significantly reduced the tumor weight of solid tumor and increased the life span
      of ascites tumor harboring mice (P < 0.01). The inhibition rate of solid tumor
      and the rate in life span were up to 47.44%, 59.49%, 63.92%, 73.42% and 52.21%,
      67.26%, 78.76%, 95.58% respectively. Meanwhile,the expression of PCNA and mutant
      p53 protein also suppressed by ethanolic extract (P < 0.05, P < 0.01).
      CONCLUSION: The stings of G. sinensis showed antitumor activity and its possible
      mechanism might be related with the expression inhibition of PCNA and mutant p53
      protein.

PMID- 16570808
TI  - [Pharmacodynamic study of Relinqing granules on bacterial pyelonephritis model in
      rats].
AB  - OBJECTIVE: To observe the effects of Relinqing granules (powder of Polygonum
      capitatum extract) on the bacterial pyelonephritis model in rats. METHOD: The rat
      bacterial pyelonephritis model was induced by injecting the escherichia coli ATCC
      25922 into kidney parenchyma. The rats were divided ramdamly into Relinqing
      groups(52.32, 26.16 g x kg(-1)), norflorin group (0.03 g x kg(-1)), model group
      and normal control group, and were given experimental drugs by gastrogavage. The
      contents of leucocytes (WBC), occult bloo (BLD), glucose (GLU), protein (PRO),
      ketones, bilirubin and urobilinagen in urine were determined. RESULT: As compared
      with the model group, Relinqing granules 6.0 g x kg(-1) (crude drug 52.32 g x kg(
      1)) could decrease significantly the contents of WBC and BLD in urine and,
      however, had no markedly effects on the other biochemical parameters of urine.
      CONCLUSION: Relinqqing granule has significant effects of decreasing urine WBC
      and BLD on the bacterial pyolonephritis in rats.

PMID- 16570809
TI  - [Study on mechanism underlying the treatment of rheumatoid arthritis by
      Keshiling].
AB  - OBJECTIVE: To explore the mechanism underlying the treatment of rheumatoid
      arthritis by Keshiling (KSL) in the rats model of FCA-induced arthritis. METHOD:
      The experimental arthritis was induced by FCA in the rats. The content of PGE2 in
      the inflammatory swelling toes was evaluated by ultraviolet spectrophotometric
      method. The ConA and LPS-induced lymphocytes proliferation and the production of
      interleukin-2 (IL-2) secreted by thymus were determined by MTT assay. RESULT:
      Results showed that the increases of lymphocyte proliferation and IL-2 production
      in AIA rats could be inhibited by KSL at the concentrations of 540 and 270 mg x
      kg(-1) in vivo and vitro. KSL at the same doses decreased the contents of PGE2 in
      inflammatory swelling toes, and the decreased A values were 25.6,16.1, 10.0 (A x
      10(3)), respectively. After administration of KSL in vivo at 540 and 270 mg x kg(
      1) the T lymphocyte proliferation were attenuated by 32.1% and 31.0%, and the
      production of IL-2 was inhibited by 17.5% and 14.0% respectively. While the
      inhibitory rates of T lymphocyte proliferation were reduced by 39.0% and 22.1%
      and the production of IL-2 was diminished by 27.3% and 18.2% respectively
      following the administration of KSL in vitro. CONCLUSION: KSL possesses the anti
      inflammation function.

PMID- 16570810
TI  - [Analysis of sphenoid sinus diseases with intracranial and/or orbital
      complications in 35 cases].
AB  - OBJECTIVE: To evaluate the clinical manifestations and treatment methods of
      sphenoid sinus diseases with intracranial and/or orbital complications, to
      provide reference for their diagnosis and treatment. METHOD: The manifestations
      and operative ways of sphenoid sinus diseases with cranial/orbital complications
      in 35 cases were retrospectively analyzed. RESULT: There were 5 cases with
      meningitis, 3 cases with cavernous sinus thrombosis, 2 cases with pituitary
      abscess, 1 case with multiple intracranial abscess, 17 cases with optic neuritis,
      8 cases with abduction nerve paralysis, 2 cases with orbital apex syndrome. All
      the patients underwent endoscopic sphenoid sinus surgery, three of them died of
      brain stem failure and carcinoma. CONCLUSION: Sphenoid sinus disease may lead to
      severe complications if the diagnosis and treatment have be delayed.

PMID- 16570811
TI  - [Study on the treatment of nasal polyposis with bleomycin A5 local injection].
AB  - OBJECTIVE: To study the treatment mechanism of nasal polyposis by locally
      injecting Bleomycin A5. METHOD: The specimens from nineteen cases with nasal
      polyposis obtained before and after treatment with Bleomycin A5 were studied with
      immunohistochemical technique and terminal deoxynucleotidyl transferase mediated
      dUTP nick end labeling (TUNEL). RESULT: The apoptosis index (AI) of eosinophil
      was (20.53 +/- 7.66) % before treatment and (44.47 +/- 8.97) % after treatment.
      There was significantly difference between them (P < 0.01). The rate of TGF-beta1
      positive expression in eosinophil after treatment (74.74 +/- 5.22) % was
      significantly lower than that before treatment (85.18 +/- 8.07) % (P < 0.05). The
      expression of TGF-beta1 in matrix was also decreased (P < 0.05). CONCLUSION:
      Bleomycin A5 could cure nasal polyposis by promoting eosinophil apoptosis and
      reducing the expression of TGF-beta1.

PMID- 16570812
TI  - [Comparison of the powered-assisted adenoidectomy with adenoid curette
      adenoidectomy].
AB  - OBJECTIVE: To compare the outcomes of powered-assisted adenoidectomy with adenoid
      curette adenoidectomy. METHOD: Thirty-four cases with adenoidal hypertrophy were
      retrospectively analyzed in Shanghai Sixth Peoples Hospital between June 2003 to
      June 2004. All the patients were followed up six to twelve months. Of 34 cases,
      18 children underwent powered-assisted adenoidectomy, and the rest underwent
      conventional transoral adenoidectomy using a curette. The surgical results were
      assessed by acoustic rhinometry. RESULT: The averaged time for endoscopic powered
      assisted adenoidectomy was 5 minutes and 15 seconds and the time for conventional
      adenoidectomy was 8 minutes and 22 seconds. There was a significant difference (P
      < 0.01) between them. The blood loss during powered-assisted and conventional
      adenoidectomy was 50 (10-125) ml and 75 (5-175) ml respectively, but there was no
      difference (P > 0.05). One case after powered-assisted adenoidectomy happened
      bleeding, and one case after conventional adenoidectomy happened dehydration.
      There were increases in the cross-sectional area at the adenoid, (0.75 +/- 0.58)
      cm2 preoperatively and (1.94 +/- 0.63) cm2 three months postoperatively, (1.99 +/
      0.44) cm2 one year after operation in powered-assisted group, and (0.80 +/-
      0.53) cm2 preoperatively and (1.83 +/- 0.81) cm2 three months postoperatively,
      (1.89 +/- 0.37) cm2 one year after operation in conventional group. Comparing the
      preoperative and postoperative cross-sectional area in both groups by acoustic
      rhinometry, a significant difference (P < 0.01) was found. CONCLUSION: Powered
      assisted adenoidectomy has the advantages of shorter surgical time, and less
      blood loss. Acoustic rhinometry is a kind of objective parameter for assessing
      the outcome of adenoidectomy.

PMID- 16570813
TI  - [Endoscopic transseptal transsphenoidal pituitary adenoma microsurgery].
AB  - OBJECTIVE: To introduce the approach and technique of endoscopic transseptal
      transsphenoidal pituitary adenoma microsurgery. METHOD: Endoscopic transseptal
      transsphenoidal pituitary adenoma microsurgery were performed in 23 patients.
      RESULT: Tumors were total resected in all of the patients. The mean volume of
      bleeding was 50 ml and there were not any severe complications. CONCLUSION:
      Compared with transsphenoidal pituitary adenoma microsurgery and endoscopic
      transsphenoidal pituitary adenoma surgery, endoscopic transseptal transsphenoidal
      pituitary adenoma microsurgery could combine the benefits of the two approaches.
      The approach has the benefit of microtrauma, convenience and could resect the
      tumor thoroughly. We could do best in treating suitable patients with good
      endoscopic technique.

PMID- 16570814
TI  - [Clinical evaluation of the styloid process by plain radiographs and three
      dimensional computed tomography].
AB  - OBJECTIVE: To investigate the relation between radiological and clinical
      diagnosis for Eagle's syndrome and to evaluate the value of plain radiograph (PR)
      and three-dimensional CT reconstructional image (3-DCT) of styloid process (SP).
      METHOD: The length of the 144 SPs from the PR was recorded and the palpation of
      the SP in tonsillar fossa was carried out in 113 patients with suspective Eagles
      syndrome. Twenty-three of 113 patients also underwent 3-DCT, so that the length
      and angulation of the 30 SPs were measured. RESULT: Seventy-eight of 113 patients
      (31 men and 47 women) were diagnosed as having Eagles syndrome. The age ranged
      from 32 to 68 years (average age: Forty-two years). A good agreement between the
      PR and the palpation was determinated, Kappa coefficient was 0.58. The difference
      value of the length of 30 SPs between the PR and the 3-DCT was (1.59 +/- 1.32)
      mm, and there were statistically significant difference of the length (t = 6.64,
      P < 0.01) on the length of SP between the PR and the 3-DCT. Positive correlation
      between the PR and the 3-DCT was found to be statistically significant (r = 0.982
      4 +/- 95% confidence interval: 0.9631, 0.9917). The mean of medial angle of SPs
      was (25.60 +/- 2.56) degrees in patients with positive palpation and (15.42 +/-
      2.79) degrees in those with negative palpation, respectively (P < 0.01) and the
      mean of anterior angle of SPs was (16.86 +/- 4.83) degrees in patients with
      positive palpation and (12.71 +/- 3.39) degrees in those with negative palpation,
      respectively (P < 0.01). The abnormal medial and anterior angles of unilateral SP
      without more than 30mm long was also objectively diagnostic of SPS in 8 patients
      with positive palpation. Four patients, whose elongated SP is too tenuous to be
      palpated preoperatively, underwent intraoral styloidectomy because of the fact
      that 3-DCT showed the tip of SPs medial and anterior deflexion. CONCLUSION:
      Despite magnifying image, the PR of SP is enough to diagnose Eagle's syndrome for
      the majority of cases. 3-DCT allows precise measurement of the length and the
      angulation of SPs, it is the best for the complementary purpose to the PR and to
      the selection of surgical approach in some cases.

PMID- 16570815
TI  - [A clinical analysis of intractable spontaneous epistaxis with 289 cases
      reviewed].
AB  - OBJECTIVE: To explore the clinical characteristics and the prevention strategy of
      intractable spontaneous epistaxis. METHOD: Two hundred and eighty-nine patients
      with intractable spontaneous epistaxis were retrospectively analyzed. RESULT:
      Intractable spontaneous epistaxis was characterized by the onset season, age,
      sex, and the associated disease. Nasal septums were the most common sites of
      bleeding. Recurrent epistaxis was mainly associated with the failure of locating
      the bleeding sites. CONCLUSION: Control of elevated blood pressure is essential
      for the prevention of intractable spontaneous epistaxis. Once epistaxis occurs,
      the importance of the first treatment for the haemostasis should be emphasized.
      For the uncontrollable epistaxis, multiple interventions are necessary.

PMID- 16570816
TI  - [Clinical observation on intranasal budesonide in chronic nonallergic rhinitis].
AB  - OBJECTIVE: An open randomized comparative study was conducted in order to observe
      the efficacy and safety about intranasal Budesonide in the treatment of chronic
      nonallergic rhinitis. METHOD: Forty-two patients with chronic nonallergic
      rhinitis were treated with Budesonide aqueous nasal spray (256 microg once daily
      intranasally) for 8 weeks. All the patients were asked for return at week 1 and
      week 8. Efficacy was evaluated by measurement of nasal symptom scores and sign
      scores at week 0, week 1 and week 8. RESULT: All the parameters measured were
      improved after treatment. Specifically, from week 0 to week 1, the scores of
      nasal secretions, itchy feeling of the nose and headache showed a significant
      decrease than that before treatment. From week 0 to week 8, the scores of nasal
      obstruction, nasal secretions, itchy feeling of the nose, closed rhinolalia and
      headache were significantly less than the record at week 0. However, there were
      not significant influences on the smell disturbances, dryness of the throat. No
      serious adverse events were reported in the study. CONCLUSION: Intranasal
      Budesonide is effective and safe in alleviating the symptoms of chronic
      nonallergic rhinitis.

PMID- 16570817
TI  - [Clinical study of juvenile nasopharyngeal angiofibroma].
AB  - OBJECTIVE: To present our experiences of diagnosis and treatment for juvenile
      nasopharyngeal angiofibroma (JNA) and to evaluate the factors influencing intra
      operative bleeding and tumor recurrence. METHOD: Forty-five patients suffered
      form JNA experienced surgical management and/or radiotherapy between January 1980
      and December 2001 were studied retrospectively. All the patients were males. The
      age ranged from 13 to 24 years with mean of 16.3 years. Three operative
      approaches were selected according to tumor stage: the traditional and modified
      transpalatal, lateral rhinotomy and craniofacial combined approach. Six cases
      received postoperative radiotherapy and 1 case received radiotherapy without
      surgery. RESULT: The tumors were completely resected in 36 cases and recurred in
      9 cases (20%) during a follow-up period of 6-84 months. Six of the 9 recurrent
      tumors were completely resected and the rest 3 were incompletely resected
      combined with postoperative radiotherapy. No recurrence was found in a follow-up
      period of 1-3 years. The tumor stage influences intraoperative bleeding and the
      incidence of recurrence. No statistically significance difference was found when
      comparing preoperative embolization of the vessels and ligature of the external
      carotid artery patients with non-embolized and control group (P = 0.554).
      CONCLUSION: (1) With the approaches of operation selected according to tumor
      stage, most of the tumors can be removed by the traditional/modified transpalatal
      and lateral rhinotomy approaches; (2) Preoperative ligature of the external
      carotid artery and embolization of the vessels feeding the tumor can not reduce
      intraoperative bleeding. The inconsistency of tumor staging in test and control
      groups may lead to this result; (3) The tumors stage influences the
      intraoperative bleeding and the incidence of recurrence; (4) Radiotherapy is an
      effective adjuvant treatment for the patients with advanced stage or recurrent
      tumors.

PMID- 16570819
TI  - [Expression of perlecan in laryngeal carcinoma cell and its significance].
AB  - OBJECTIVE: To study the expression of perlecan in human laryngeal carcinoma cells
      and its significance. METHOD: The expression of perlecan mRNA in human laryngeal
      carcinoma cells, Hep-2 cells were investigated by using the techniques of semi
      quantify RT-PCR. The expression of perlecan in the Hep-2 cells was investigated
      by using the techniques of immunohistochemistry. RESULT: It showed that the
      expression level of perlecan and perlecan mRNA significantly increased in Hep-2
      cells as compared with the normal cells, Hacat cells (P < 0.01). CONCLUSION:
      These data raise the possibility that perlecan many play key roles in the
      growth,invasion and metastasis of human laryngeal carcinoma cells through either
      a paracrine or an autocrine mechanism.

PMID- 16570818
TI  - [The significance and effect of substance P on the expression of RANTES mRNA in
      allergic rhinitis].
AB  - OBJECTIVE: To study the significance and effect of SP on the expression of RANTES
      mRNA in allergic rhinitis (AR), and deeply understand the pathogenesis of AR.
      METHOD: The model of AR was established in randomly selected healthy guinea pigs
      by using ovalbumin. Then the nasal dripping of SP was used to challenge the AR
      groups, as compared with the normal controls, in observation of the symptoms and
      histopathologic changes in the nasal mucosa. The number of eosinophil in the
      nasal lavage fluid was also counted. By means of RT-PCR, the expressions of
      RANTES mRNA in the nasal mucosa of the different groups were quantitatively
      compared. RESULT: SP challenge induced similar AR symptoms in the normal group
      and aggravated AR symptoms and inflammation in the nasal mucosa in the model of
      AR groups. The expression level of RANTES mRNA (P < 0.05) and the number of
      eosinophil (P < 0.01) in AR groups increased significantly after challenged with
      SP. CONCLUSION: In the pathogenesis of AR, SP induces the expression of chemokine
      RANTES in nasal mucosa, promotes eosinophil chemotaxis and migration, induces and
      aggravates the allergic inflammatory reaction in AR.

PMID- 16570820
TI  - Unmet challenges in HIV therapy and potential of stampidine.

PMID- 16570821
TI  - Stampidine as a novel nucleoside reverse transcriptase inhibit with potent anti
      HIV activity.
AB  - Stavudine (STV, d4T, 2',3'-didehydro-3'-deoxythymidine, CAS 3056-17-5) is a
      standard anti-HIV drug. Stampidine (STAMP, DDE-113, HI-113, N-[p-(4-bromophenyl)
      2',3'-didehydro-3'-deoxy-5'-thymidylyl]-L-alanine methyl ester, CAS 217178-62-6)
      is a novel aryl phosphate derivative of stavudine with more potent anti-HIV
      activity and more favorable pharmacodynamic features. The remarkable potency of
      stampidine against clinical HIV-1 isolates with NRTI- or NNRTI-resistance (NRTI,
      nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse
      transcriptase inhibitor) warrants the further development of this new anti-HIV
      agent.

PMID- 16570822
TI  - Large-scale synthesis and formulation of GMP-grade stampidine, a new anti-HIV
      agent.
AB  - The arylphosphoramidate derivative of stavudine (STV, d4T, 2,3'-didehydro-3'
      deoxythymidine, CAS 3056-17-5), stampidine (STAMP, DDE-113, HI-113, N-[p-(4
      bromophenyl)-2',3'-didehydro-3'-deoxy-5'-thymidylyl]-L-alanine methyl ester, CAS
      217178-62-6), is a novel anti-HIV agent. STAMP was prepared under current Good
      Manufacturing Practice (cGMP) conditions on the scale of kilograms. Solid STAMP
      was subsequently formulated as a capsule under GMP conditions for oral
      administration.

PMID- 16570823
TI  - Synthesis, separation and anti-HIV activity of distereoisomers of N-[p-(4
      bromophenyl) -2',3'-didehydro-3'-deoxy-5'-thymidylyl]-L-alanine methyl ester
      (stampidine).
AB  - The distereoisomers of stampidine (STAMP, DDE-113, HI-113, N-[p-(4-bromophenyl)
      2'3'-didehydro-3'-deoxy-5'-thymidylyl]-L-alanine methyl ester, CAS 217178-62-6)
      were separated using two different procedures. The first method involved
      separation of the isomers by fractional crystallization, and the second method
      utilized a preparative HPLC. Both isomers were active against the HIV-1 strain
      HTLV(IIIB) and neither isomer was more or less active than distereoisomeric
      mixture of stampidine.

PMID- 16570824
TI  - Developmental safety profile of the anti-HIV agent stampidine in rabbits.
AB  - Stampidine (STAMP, DDE-113, HI-113, N-[p-(4-bromophenyl)-2',3'-didehydro-3'-deoxy
      5'-thymidylyl]-L-alanine methyl ester, CAS 217178-62-6) is a novel aryl phosphate
      derivative of stavudine (STV, d4T, 2',3'-didehydro-3'-deoxythymidine, CAS 3056-17
      5) with potent anti-HIV activity. The reproductive and developmental safety
      profile of STAMP was evaluated in mated New Zealand white rabbits. STAMP did not
      adversely affect the reproductive health of female rabbits and it lacked
      teratogenicity or other developmental toxicity in their progeny.

PMID- 16570826
TI  - In vivo pharmacokinetics and toxicity profile of the anti-HIV agent stampidine in
      dogs and feline immunodeficiency virus-infected cats.
AB  - The pharmacokinetics and toxicity profile of stampidine (STAMP, DDE-113, HI-113,
      N-[p-(4-bromophenyl)-2',3'-didehydro-3'-deoxy-5'-thymidylyl]-L-alanine methyl
      ester, CAS 217178-62-6) were studied in beagle dogs and feline immunodeficiency
      virus-infected domestic cats. Therapeutic plasma concentrations of STAMP 3-4 logs
      higher than its IC50 value can be achieved after its p.o. administration to dogs
      as well as cats at the 100 mg/kg nontoxic dose level. In accordance with its
      safety profile in rodent species, a 4- to 7-week STAMP treatment course with
      twice daily administration of hard gelatin capsules containing 25-100 mg/kg (50
      200 mg/kg/ day) STAMP was very well-tolerated by dogs and cats at cumulative dose
      levels as high as 8.4 g/kg. Except for the sporadic occurrence of nausea and
      vomiting after its administration and elevation of serum ALT levels in some of
      the cats, STAMP therapy was not associated with any clinical or laboratory
      evidence of toxicity. No STAMP-related toxic lesions were found in any of the
      organs from STAMP-treated cats or dogs. These findings encourage the further
      development of stampidine for possible clinical use in HIV-infected persons.

PMID- 16570825
TI  - Site-specific enzymatic activation of the anti-HIV agent stampidine.
AB  - Stampidine (STAMP, DDE-113, HI-113, N-[p-(4-bromophenyl)-2',3'-didehydro-3'-deoxy
      5'-thymidylyl]-L-alanine methyl ester, CAS 217178-62-6) and two stampidine
      analogs containing ethyl or t-butyl groups were synthesized and their rates of
      enzymatic activation were compared side-by-side. Enzymes such as lipase, esterase
      and protease did not hydrolyze the butyl substituted STAMP analog. These
      experimental results show that the site of attack for the enzymatic hydrolysis of
      STAMP is the ester side chain of the molecule.

PMID- 16570827
TI  - Potency of stampidine against multi-nucleoside reverse transcriptase inhibitor
      resistant human immunodeficiency viruses.
AB  - The in vitro potency of stampidine (STAMP, DDE-113, HI-113, N-[p-(4-bromophenyl)
      2',3'-didehydro-3'-deoxy-5'-thymidylyl]-L-alanine methyl ester, CAS 217178-62-6)
      was examined against 8 clinical non-B subtype HIV-1 isolates with resistance to
      stavudine (STV, d4T), adefovir and tenofovir, 19 clinical zidovudine-resistant
      HIV-1 isolates, and 6 recombinant HIV-1 clones with multi-resistance against
      nucleoside reverse transcriptase inhibitors. Stampidine exhibited potent anti-HIV
      activity against each one of these 33 HIV-1 isolates with subnanomolar to
      nanomolar IC50 values.

PMID- 16570828
TI  - Exploring the connection between oral health and overall health.

PMID- 16570829
TI  - Commission created to work on supporting and bolstering Medicaid.

PMID- 16570830
TI  - Robots, bionics, and bioengineered replacement parts in dentistry.

PMID- 16570831
TI  - Oral health assessment for California schoolchildren: are organized dentistry and
      the California legislature receptive to the concept?
AB  - The need to improve the oral health of children in our state has been well
      documented in the past 10 years. The concept, however, of intervention by
      identification of the dental disease process on a widespread basis at the age of
      school entrance has only recently been advanced. In view of the fact that dental
      caries remains the No. 1 chronic disease of childhood, the need for intervention
      no later than the time a child enrolls in primary school may be a way to reduce
      the oral health problem before it becomes emergent.

PMID- 16570833
TI  - Dentists who represent themselves when leasing office space have fools for
      clients.

PMID- 16570832
TI  - Jonathan Taft: dentistry's great forgotten hero.
AB  - One of the greatest figures in the development of the dental profession to the
      high status it enjoys today is all but forgotten. Jonathan Taft was dean of the
      second dental school in the world and wrote the most important clinical textbook
      of his time, one that was reprinted in many editions over a quarter of a century.
      Later appointed dean of the new University of Michigan Dental School, he
      instituted innovations in admission requirements and course of study that were
      copied by all subsequent schools and are the standards adhered to today. The
      editor of one of the most important dental journals for 44 years, a record
      unmatched to this day, he set the standards for modern dental periodical
      literature that have done so much to elevate dentistry that today it stands on a
      par with medicine as a truly science-based profession. He served dentistry in
      many capacities: president of the American Dental Association, founder of the
      National Association of Dental Faculties, and founder of the National Association
      of Dental Examiners. Over his lifetime, he published almost 200 professional
      papers and probably attended and lectured at more dental meetings than anyone of
      his day and since. His memory should be resurrected, and the profession must be
      made aware of the great debt it owes to this intrepid fighter for a better dental
      profession.

PMID- 16570834
TI  - California Dental Association. Code of Ethics.

PMID- 16570835
TI  - Napolean's tooth: junk or jewel?

PMID- 16570836
TI  - Implications of the impact factor.

PMID- 16570837
TI  - Mysteries and mazes: parents' experiences of children with developmental
      coordination disorder.
AB  - BACKGROUND: Children with Developmental Coordination Disorder (DCD) represent 5
      to 6% of the school-aged population and are often seen by occupational therapists
      in the school system. Although a family-centred approach has been identified as
      best practice in pediatric care, the perspective of parents is often overlooked
      both in research and in practice. PURPOSE AND METHOD: In this study, a
      qualitative, phenomenological approach was adopted to explore the insights and
      experiences of 13 parents of children with DCD. Each parent participated in two
      in-depth interviews and completed a set of questionnaires. RESULTS: Analysis of
      the study findings led to three primary themes that captured the experience of
      parents as they attempted to understand and get help for their child. The theme
      of unravelling the mystery highlights parents' impressions of their child's
      difficulties. The second theme of negotiating the maze refers to the many
      pathways followed by families as they sought to affirm their perceptions and
      obtain services for their child and the final theme of parenting dilemmas
      underscores some of the common challenges faced by parents in trying to deal with
      their child's limitations. PRACTICE IMPLICATIONS: For occupational therapists,
      the study findings illustrate the importance of focusing on occupational
      performance issues for children with DCD, facilitating the understanding of
      parents, and the need for early intervention.

PMID- 16570838
TI  - The experience of senior stroke survivors: factors in community participation
      among wheelchair users.
AB  - PURPOSE: This qualitative study investigated the lived experience of senior
      stroke survivors who used prescribed wheelchairs in their home and community.
      METHODS: The study involved semi-structured, in-depth interviews that were
      conducted with 10 participants, aged 70 to 80, who had used a wheelchair for a
      mean of 5.6 years. All participants used manual wheelchairs and two additionally
      used a power wheelchair and a scooter. RESULTS: A constant comparative inductive
      method of analysis of the data yielded several themes which are examined within
      the International Classification of Functioning, Disability and Health framework
      of body functions and structure, activity limitations, participation, and
      contextual factors. Overall, the wheelchair, manual or power, was an enabler of
      community participation among the participants. However, the wheelchair's use
      also created problems, such as limiting destinations and creating increased
      dependence on others. PRACTICE IMPLICATIONS: A balance scale model was proposed
      to facilitate an understanding of how the factors affecting community
      participation interact in this population. This model can assist occupational
      therapists who prescribe wheelchairs for stroke clients for use in the community.

PMID- 16570839
TI  - [Cognitive training interventions for normal aging, mild cognitive impairment and
      Alzheimer's].
AB  - BACKGROUND: In the past few years, occupational therapists have been increasingly
      working with geriatric clients and have used interventions focused on enhancing
      independance and quality of life. In this area of practice, the cognitive
      training intervention aimed more specifically at memory disorders, is a promising
      intervention for the area of aging and occupational therapy. PURPOSE: The aim of
      this literature review is to present an overview of the fundamentals, objectives
      and procedures of the cognitive training intervention used with the following
      populations: aging people presenting a memory disorder associated with normal
      aging with mild cognitive impairment or with Alzheimer's disease. PRACTICE
      IMPLICATIONS: A discussion on the cognitive management of memory is presented
      with respect to the cognitive characteristics of each of these clients.

PMID- 16570840
TI  - Listening for recovery: the vocational success of people living with mental
      illness.
AB  - BACKGROUND: Mental health occupational therapists work with some individuals who
      want employment but who are not successful at finding or keeping a job. PURPOSE:
      The purpose of this qualitative study was to suggest factors contributing to
      vocational success. METHOD: The investigators interviewed 8 participants who were
      recovering from psychosis. The interview texts were coded and analyzed for
      emerging themes. RESULTS: Three themes emerged that describe how the participants
      achieved vocational success: self-assessing their mental health regularly,
      actively working to maintain and improve their mental health, and striving to
      feel connected to others at work. The results are consistent with previous
      studies that found that a positive fit between a worker and the workplace is
      linked to the worker feeling connected to and valued by the workplace. PRACTICE
      IMPLICATIONS: This study suggests that supporting the ways individuals assess and
      promote their own mental health and recovery will contribute to their success at
      work. Occupational therapists are urged to help people find workplaces where they
      feel encouraged and comfortable as this appears to be an important factor in
      vocational success.

PMID- 16570841
TI  - Using occupation to facilitate self-awareness in people who have acquired brain
      injury: a pilot study.
AB  - BACKGROUND: Impaired self-awareness in people who have had an acquired brain
      injury (ABI) is a complex phenomenon that impedes rehabilitation progress and
      outcome. PURPOSE: This pilot study investigated the effect of an occupation-based
      intervention program on the self-awareness and emotional status of people after
      ABI. Four male adults with impaired self-awareness following ABI participated in
      this study. Each received a 10-week individualized program that focused on the
      performance of three occupations for 1 to 2 hours per week. A facilitative
      approach was taken, using techniques to improve self-awareness described in the
      literature. Repeated measures of participants'self-awareness and emotional status
      were taken pre- and post-intervention, and analyzed descriptively. RESULTS:
      Results indicated preliminary support for the effectiveness of the program in
      facilitating participants' self-awareness. However, consideration of baseline and
      follow-up data indicated a complex picture. Increased anxiety was found to
      accompany improvements in participants' self-awareness in all four cases.
      PRACTICE IMPLICATIONS: This study will assist occupational therapists with
      program development for clients who have had an acquired brain injury.

PMID- 16570843
TI  - The almost-forgotten fifth nucleotide in DNA: an introduction.

PMID- 16570842
TI  - Pressure ulcers and occupational therapy practice: a Canadian perspective.
AB  - BACKGROUND: Occupational therapists are involved in the prevention and management
      of pressure ulcers. While many therapists identify challenges with their clinical
      practice in this area, there is little information available regarding specific
      occupational therapy interventions or effectiveness. PURPOSE: The goal of this
      study was to gain a national perspective of practice in Canada and identify
      directions and trends in the management of pressure ulcers. METHOD: A survey was
      distributed to occupational therapists at 75 facilities across Canada, soliciting
      information on intervention, practice issues and satisfaction with their
      practice. RESULTS: Thirty-seven therapists from 36 facilities responded,
      answering questions about risk assessment tools, referral patterns, interventions
      and decision-making models, satisfaction with practice, intervention rationales,
      and recommendations for change. Risk assessment, early intervention and
      continuity of care were identified as concerns, with a lack of resources
      identified as a limitation to practice. Seating and positioning were common
      interventions. PRACTICE IMPLICATIONS: This information can be used by clinicians
      to direct best practice and professional development goals. Further research is
      indicated in risk assessment, team collaboration and mattress prescription.

PMID- 16570844
TI  - Replication and translation of epigenetic information.
AB  - Most cells in multicellular organisms contain identical genetic information but
      differ in their epigenetic information. The latter is encoded at the molecular
      level by post-replicative methylation of certain DNA bases (in mammals 5-methyl
      cytosine at CpG sites) and multiple histone modifications in chromatin. In
      addition, higher-order chromatin structures are generated during differentiation,
      which might impact on genome expression and stability. The epigenetic information
      needs to be "translated" in order to define specific cell types with specific
      sets of active and inactive genes, collectively called the epigenome. Once
      established, the epigenome needs to be "replicated" at each cell division cycle,
      i.e., both genetic and epigenetic information have to be faithfully duplicated,
      which implies a tight coordination between the DNA replication machinery and
      epigenetic regulators. In this review, we focus on the molecules and mechanisms
      responsible for the replication and translation of DNA methylation in mammals as
      one of the central epigenetic marks.

PMID- 16570845
TI  - DNA methyltransferases: facts, clues, mysteries.
AB  - DNA methylation plays a pivotal role during development in mammals and is central
      to transcriptional silencing. The DNA methyltransferases (DNMTs) are responsible
      for the generation of genomic methylation patterns leading to gene silencing, but
      the underlying molecular basis remains largely shrouded in mystery. Here we
      review our current understanding of the mechanisms by which DNMTs repress
      transcription and how they are targeted to preferred DNA sequences. Emerging
      evidence points to an essential and intricate web of interactions between DNMTs
      and the chromatin environment in which they function. The recent identification
      of novel transcription factors recruiting the DNMTs may open new avenues of
      research into the origin of DNA methylation patterns. Thanks to these emerging
      clues, researchers have begun to lift the veil on the multi-faceted DNMTs, but
      there remains fascinating work ahead for whoever wants to fully understand DNMTs
      and their role in the mammalian cell.

PMID- 16570846
TI  - DNA methylation in plants.
AB  - DNA in plants is highly methylated, containing 5-methylcytosine (m5C) and N6
      methyladenine (m6A); m5C is located mainly in symmetrical CG and CNG sequences
      but it may occur also in other non-symmetrical contexts. m6A but not m5C was
      found in plant mitochondrial DNA. DNA methylation in plants is species-, tissue-,
      organelle- and age-specific. It is controlled by phytohormones and changes on
      seed germination, flowering and under the influence of various pathogens (viral,
      bacterial, fungal). DNA methylation controls plant growth and development, with
      particular involvement in regulation of gene expression and DNA replication. DNA
      replication is accompanied by the appearance of under-methylated, newly formed
      DNA strands including Okazaki fragments; asymmetry of strand DNA methylation
      disappears until the end of the cell cycle. A model for regulation of DNA
      replication by methylation is suggested. Cytosine DNA methylation in plants is
      more rich and diverse compared with animals. It is carried out by the families of
      specific enzymes that belong to at least three classes of DNA methyltransferases.
      Open reading frames (ORF) for adenine DNA methyltransferases are found in plant
      and animal genomes, and a first eukaryotic (plant) adenine DNA methyltransferase
      (wadmtase) is described; the enzyme seems to be involved in regulation of the
      mitochondria replication. Like in animals, DNA methylation in plants is closely
      associated with histone modifications and it affects binding of specific proteins
      to DNA and formation of respective transcription complexes in chromatin. The same
      gene (DRM2) in Arabidopsis thaliana is methylated both at cytosine and adenine
      residues; thus, at least two different, and probably interdependent, systems of
      DNA modification are present in plants. Plants seem to have a restriction
      modification (R-M) system. RNA-directed DNA methylation has been observed in
      plants; it involves de novo methylation of almost all cytosine residues in a
      region of siRNA-DNA sequence identity; therefore, it is mainly associated with
      CNG and non-symmetrical methylations (rare in animals) in coding and promoter
      regions of silenced genes. Cytoplasmic viral RNA can affect methylation of
      homologous nuclear sequences and it maybe one of the feedback mechanisms between
      the cytoplasm and the nucleus to control gene expression.

PMID- 16570847
TI  - De novo methylation, long-term promoter silencing, methylation patterns in the
      human genome, and consequences of foreign DNA insertion.
AB  - This chapter presents a personal account of the work on DNA methylation in viral
      and mammalian systems performed in the author's laboratory in the course of the
      past 30 years. The text does not attempt to give a complete and meticulous
      account of the work accomplished in many other laboratories; in that sense it is
      not a review of the field in a conventional sense. Since the author is also one
      of the editors of this series of Current Topics in Immunology and Microbiology on
      DNA methylation, to which contributions by many of our colleagues in this field
      have been invited, the author's conscience is alleviated that he has not cited
      many of the relevant and excellent reports by others. The choice of viral model
      systems in molecular biology is well founded. Over many decades, viruses have
      proved their invaluable and pioneering role as tools in molecular genetics. When
      our interest turned to the demonstration of genome-wide patterns of DNA
      methylation, we focused mainly on the human genome. The following topics in DNA
      methylation will be treated in detail: (1) The de novo methylation of integrated
      foreign genomes; (2) the long-term gene silencing effect of sequence-specific
      promoter methylation and its reversal; (3) the properties and specificity of
      patterns of DNA methylation in the human genome and their possible relations to
      pathogenesis; (4) the long-range global effects on cellular DNA methylation and
      transcriptional profiles as a consequence of foreign DNA insertion into an
      established genome; (5) the patterns of DNA methylation can be considered part of
      a cellular defense mechanism against foreign or repetitive DNA; which role has
      food-ingested DNA played in the elaboration of this mechanism? The interest in
      problems related to DNA methylation has spread-like the mechanism itself-into
      many neighboring fields. The nature of the transcriptional programs orchestrating
      embryonal and fetal development, chromatin structure, genetic imprinting, genetic
      disease, X chromosome inactivation, and tumor biology are but a few of the areas
      of research that have incorporated studies on the importance of the hitherto
      somewhat neglected fifth nucleotide in many genomes. Even the fly researchers now
      have to cope with the presence of this nucleotide, in however small quantities it
      exists in the genome of their model organism, at least during embryonal
      development. The bulk of the experimental work accomplished in the author's
      laboratory has been shouldered by many very motivated undergraduate and graduate
      students and by a number of talented postdoctoral researchers. Their
      contributions are reflected in the list of references in this chapter. We have
      also had the good luck to receive funding through a number or organizations as
      acknowledged.

PMID- 16570848
TI  - Establishment and maintenance of DNA methylation patterns in mammals.
AB  - In mammals, CpG methylation patterns are established and maintained during
      development by the Dnmt1 and Dnmt3 families of DNA methyltransferases. These
      enzymes share conserved catalytic motifs in their C-terminal regions, but have
      unique N-terminal regulatory domains. Studies over the past several years have
      shed light on the molecular mechanisms by which DNA methylation patterns are
      regulated. This review focuses on recent advances in defining the functional
      domains of DNA methyltransferases and identifying interacting proteins that may
      contribute to the functional specializations of these enzymes.

PMID- 16570850
TI  - Familial hydatidiform molar pregnancy: the germline imprinting defect hypothesis?
AB  - Imprinting is the uniparental expression of a set of genes. Somatic cells carry
      two haploid sets of chromosomes, one maternal and one paternal, while germ cells
      contain only one of the two forms of chromosomes, male or female. This implies
      that during early embryogenesis the cells committed for developing the future
      germ cell lineage, the primordial germ cells, which are diploid, have to undergo
      a total chromosome reprogramming process. This process is delicately controlled
      during gametogenesis to ensure that males and females have only their respective
      form of gametes. The machinery involved in this process is yet poorly defined.
      Familial hydatidiform molar (HM) pregnancy is an abnormal form of pregnancy
      characterized by hydropic degeneration of placental villi and abnormal, or
      absence of, embryonic development. To date, the molecular defect causing this
      condition is unknown. However, in a few studied cases, the presence of paternal
      methylation patterns on the maternal chromosomes was observed. In this chapter,
      we summarize what is known about methylation aberrations in HMs and examine more
      closely the proposed hypothesis of a maternal germline imprinting defect.

PMID- 16570849
TI  - Molecular enzymology of mammalian DNA methyltransferases.
AB  - DNA methylation is an essential modification of DNA in mammals that is involved
      in gene regulation, development, genome defence and disease. In mammals 3
      families of DNA methyltransferases (MTases) comprising (so far) 4 members have
      been found: Dnmt1, Dnmt2, Dnmt3A and Dnmt3B. In addition, Dnmt3L has been
      identified as a stimulator of the Dnmt3A and Dnmt3B enzymes. In this review the
      enzymology of the mammalian DNA MTases is described, starting with a depiction of
      the catalytic mechanism that involves covalent catalysis and base flipping.
      Subsequently, important mechanistic features of the mammalian enzyme are
      discussed including the specificity of Dnmt1 for hemimethylated target sites, the
      target sequence specificity of Dnmt3A, Dnmt3B and Dnmt2 and the flanking sequence
      preferences of Dnmt3A and Dnmt3B. In addition, the processivity of the
      methylation reaction by Dnmt1, Dnmt3A and Dnmt3B is reviewed. Finally, the
      control of the catalytic activity of mammalian MTases is described that includes
      the regulation of the activity of Dnmtl by its N-terminal domain and the
      interaction of Dnmt3A and Dnmt3B with Dnmt3L. The allosteric activation of Dnmt1
      for methylation at unmodified sites is described. Wherever possible, correlations
      between the biochemical properties of the enzymes and their physiological
      functions in the cell are indicated.

PMID- 16570851
TI  - Dual inheritance.
AB  - Genetic inheritance in higher organisms normally refers to the transmission of
      information from one generation to the next. Nevertheless, there is also
      inheritance in somatic cells, characterised by the phenotypic stability of
      differentiated cells that divide (such as fibroblasts and lymphocytes), and also
      mitosis of stem line cells, which gives rise to another stem line daughter cell,
      and one that will differentiate. Thus, there is a dual inheritance systems in
      these organisms, one of which is genetic and the other epigenetic. In the latter,
      heritable information is superimposed on DNA sequences, and one well-known
      mechanism is heritable methylation of cytosine. Much information will come from
      the human epigenome project that will reveal the patterns of DNA methylation in
      distinct differentiated cells. There have also been innumerable studies on the
      abnormal de novo methylation and silencing of tumour suppressor genes in cancer
      cells.

PMID- 16570852
TI  - Mutagenesis at methylated CpG sequences.
AB  - 5-Methylcytosine in DNA is genetically unstable. Methylated CpG (mCpG) sequences
      frequently undergo mutation resulting in a general depletion of this dinucleotide
      sequence in mammalian genomes. In human genetic disease- and cancer-relevant
      genes, mCpG sequences are mutational hotspots. It is an almost universally
      accepted dogma that these mutations are caused by random deamination of 5
      methylcytosines. However, it is plausible that mCpG transitions are not caused
      simply by spontaneous deamination of 5-methylcytosine in double-stranded DNA but
      by other processes including, for example, mCpG-specific base modification by
      endogenous or exogenous mutagens or, alternatively, by secondary factors
      operating at mCpG sequences and promoting deamination. We also discuss that mCpG
      sequences are favored targets for specific exogenous mutagens and carcinogens.
      When adjacent to another pyrimidine, 5-methylcytosine preferentially undergoes
      sunlight-induced pyrimidine dimer formation. Certain polycyclic aromatic
      hydrocarbons form guanine adducts and induce G to T transversion mutations with
      high selectivity at mCpG sequences.

PMID- 16570853
TI  - Cytosine methylation and DNA repair.
AB  - Cytosine methylation is a common form of post-replicative DNA modification seen
      in both bacteria and eukaryotes. Modified cytosines have long been known to act
      as hotspots for mutations due to the high rate of spontaneous deamination of this
      base to thymine, resulting in a G/T mismatch. This will be fixed as a C-->T
      transition after replication if not repaired by the base excision repair (BER)
      pathway or specific repair enzymes dedicated to this purpose. This
      hypermutability has led to depletion of the target dinucleotide CpG outside of
      special CpG islands in mammals, which are normally unmethylated. We review the
      importance of C-->T transitions at non-island CpGs in human disease: When these
      occur in the germline, they are a common cause of inherited diseases such as
      epidermolysis bullosa and mucopolysaccharidosis, while in the soma they are
      frequently found in the genes for tumor suppressors such as p53 and the
      retinoblastoma protein, causing cancer. We also examine the specific repair
      enzymes involved, namely the endonuclease Vsr in Escherichia coli and two members
      of the uracil DNA glycosylase (UDG) superfamily in mammals, TDG and MBD4. Repair
      brings its own problems, since it will require remethylation of the replacement
      cytosine, presumably coupling repair to methylation by either the maintenance
      methylase Dnmt1 or a de novo enzyme such as Dnmt3a. Uncoupling of methylation
      from repair may be one way to remove methylation from DNA. We also look at the
      possible role of specific cytosine deaminases such as Aid and Apobec in
      accelerating deamination of methylcytosine and consequent DNA demethylation.

PMID- 16570854
TI  - Functional diversity of chemokines and chemokine receptors in response to viral
      infection of the central nervous system.
AB  - Encounters with neurotropic viruses result in varied outcomes ranging from
      encephalitis, paralytic poliomyelitis or other serious consequences to relatively
      benign infection. One of the principal factors that control the outcome of
      infection is the localized tissue response and subsequent immune response
      directed against the invading toxic agent. It is the role of the immune system to
      contain and control the spread of virus infection in the central nervous system
      (CNS), and paradoxically, this response may also be pathologic. Chemokines are
      potent proinflammatory molecules whose expression within virally infected tissues
      is often associated with protection and/or pathology which correlates with
      migration and accumulation of immune cells. Indeed, studies with a neurotropic
      murine coronavirus, mouse hepatitis virus (MHV), have provided important insight
      into the functional roles of chemokines and chemokine receptors in participating
      in various aspects of host defense as well as disease development within the CNS.
      This chapter will highlight recent discoveries that have provided insight into
      the diverse biologic roles of chemokines and their receptors in coordinating
      immune responses following viral infection of the CNS.

PMID- 16570855
TI  - Cytokine and chemokine networks: pathways to antiviral defense.
AB  - The complex interplays between cytokines and chemokines are emerging as key
      communication signals in the shaping of innate and adaptive immune responses
      against foreign pathogens, including viruses. In particular, the virus-induced
      expression of cytokine and chemokine profiles drives the recruitment and
      activation of immune effector cells to sites of tissue infection. Under the
      conditions of infection with murine cytomegalovirus (MCMV), a herpesvirus with
      pathogenic potential, early immune functions are essential in the control of
      virus replication and virus-induced pathology. The coordinated MCMV-induced
      cytokine and chemokine responses promote effective natural killer (NK) cell
      recruitment and function, and ultimately MCMV clearance. The studies highlighted
      in this chapter illustrate in vivo pathways mediated by innate cytokines in
      regulating chemokine responses that are vital for localized antiviral defenses.

PMID- 16570857
TI  - Influence of proinflammatory cytokines and chemokines on the neuropathogenesis of
      oncornavirus and immunosuppressive lentivirus infections.
AB  - Retroviral infection of the CNS can lead to severe debilitating neurological
      diseases in humans and other animals. Four general types of pathogenic effects
      with various retroviruses have been observed including: hemorrhage (TR1.3),
      spongiform encephalopathy (CasBrE, FrCasE, PVC211, NT40, Mol-ts1), demyelination
      with inflammatory lesions (HTLV-1, visna, CAEV), and encephalopathy with gliosis
      and proinflammatory chemokines and cytokines, usually with microglial giant cells
      and nodules [human immunodeficiencyvirus (HIV), feline immunodeficiencyvirus
      (FIV), simian immunodeficiency virus (SIV), Fr98]. This review focuses on this
      fourth group of retroviruses. In this latter group, proinflammatory cytokine and
      chemokine upregulation accompanies the disease process, and may influence
      pathogenesis by direct effects on resident CNS cells. The review first discusses
      the Fr98 murine polytropic virus system with particular reference to the roles of
      cytokines and chemokines in the pathogenic process. The Fr98 data are then
      compared and contrasted to the cytokine and chemokine data in the lentivirus
      systems, HIV, SIV, and FIV. Finally, various mechanisms are presented by which
      tumor necrosis factor (TNF) and several chemokines may alter the pathogenesis of
      retrovirus infection of the CNS.

PMID- 16570856
TI  - Herpes simplex virus and the chemokines that mediate the inflammation.
AB  - Herpes simplex viruses (HSV) are highly pervasive pathogens in the human host
      with a seroconversion rate upwards of 60% worldwide. HSV type 1 (HSV-1) is
      associated with the disease herpetic stromal keratitis, the leading cause of
      infectious corneal blindness in the industrialized world. Individuals suffering
      from genital herpes associated with HSV type 2 (HSV-2) are found to be two- to
      threefold more susceptible in acquiring human immunodeficiency virus (HIV). The
      morbidity associated with these infections is principally due to the inflammatory
      response, the development of lesions, and scarring. Chemokines have become an
      important aspect in understanding the host immune response to microbial pathogens
      due in part to the timing of expression. In this paper, we will explore the
      current understanding of chemokine production as it relates to the orchestration
      of the immune response to HSV infection.

PMID- 16570858
TI  - HIV-1 coreceptors and their inhibitors.
AB  - Entry of human immunodeficiency virus (HIV) into target cells is mediated by the
      viral Envelope glycoprotein (Env) and its coordinated interaction with a receptor
      (CD4) and a coreceptor (usually the chemokine receptors CCR5 or CXCR4). This
      review describes the identification of chemokine receptors as coreceptors for HIV
      1 Env-mediated fusion, the determinants of chemokine receptor usage, and the
      impact of nonfunctional chemokine receptor alleles on HIV-1 resistance and
      disease progression. Due to the important role of chemokine receptors in HIV-1
      entry, inhibitors of these coreceptors are good candidates for blocking entry and
      development of antiretroviral therapies. We discuss the different CCR5- and CXCR4
      based antiretroviral drugs that have been developed thus far, highlighting the
      most promising drug candidates. Resistance to these coreceptor inhibitors as well
      as the impact of these drugs on clinical monitoring and treatment are also
      discussed.

PMID- 16570859
TI  - A viral conspiracy: hijacking the chemokine system through virally encoded
      pirated chemokine receptors.
AB  - Several herpesviruses and poxviruses contain genes encoding for G protein-coupled
      receptor (GPCR) proteins that are expressed on the surface of infected host cells
      and/or the viral envelope. Most of these membrane-associated proteins display
      highest homology to the subfamily of chemokine receptors known to play a key role
      in the immune system. Virally encoded chemokine receptors have been modified
      through evolutionary selection both in chemokine binding profile and signaling
      capacity, ultimately resulting in immune evasion and cellular reprogramming in
      favor of viral survival and replication. Insight in the role of virally encoded
      GPCRs during the viral lifecycle may reveal their potential as future drug
      targets.

PMID- 16570860
TI  - Types of filtration.
AB  - There are a multitude of filter designs and mechanisms utilized within the
      biopharmaceutical industry. Prefilters are commonly pleated or wound filter
      fleeces manufactured from melt-blown random fiber matrices. These filters are
      used to remove a high contaminant content within the fluid. Prefilters have a
      large band of retention ratings and can be optimized to all necessary
      applications. The most common application for prefilters is to protect membrane
      filters, which are tighter and more selective than prefilters. Membrane filters
      are used to polish or sterilize fluids. These filters need to be integrity
      testable to assess whether or not they meet the performance criteria. Cross-flow
      filtration can be utilized with micro- or ultrafiltration membranes. The fluid
      sweeps over the membrane layer and therefore keeps it unblocked. This mode of
      filtration also allows diafiltration or concentration of fluid streams.
      Nanofilters are commonly used as viral removal filters. The most common retention
      rating of these filters is 20 or 50 nm.

PMID- 16570861
TI  - Modus of filtration.
AB  - Experience teaches that particles larger than the pores of a filter cannot
      negotiate its passage. Other retention mechanisms are less obvious than sieve
      retention or size exclusion. They are electrical in nature, and find expression
      in the bonding alliances that mutually attract (or repel) filters and particles.
      The influence of hydrogen bonds, of van der Waals forces, of hydrophobic
      adsorptions, and of transient polarities on particle retentions are set forth in
      terms of the double electrical layer concept that also governs colloidal
      destabilizations. The origins of differences in membrane porosities is explained,
      as also the importance of the filtration conditions. The singularity of the
      particle-fluid-filter relationship on organism and/or pore size alteration is
      stressed.

PMID- 16570862
TI  - Microfiltration membranes: characteristics and manufacturing.
AB  - Membrane filtration is used within a multitude of processes ranging from dialysis
      to desalination processes to sterilizing filtration in the pharmaceutical
      industry. Membranes, nevertheless, have to have special characteristics and
      properties to serve such specific applications. Microfiltration membranes are
      utilized in a large range of membrane polymers and structures, which all have
      individual production process steps to achieve consistently the same membrane
      parameters. This chapter discusses membrane polymers and production processes in
      detail.

PMID- 16570863
TI  - Filter construction and design.
AB  - Sterilizing and pre-filters are manufactured in different formats and designs.
      The criteria for the specific designs are set by the application and the
      specifications of the filter user. The optimal filter unit or even system
      requires evaluation, such as flow rate, throughput, unspecific adsorption, steam
      sterilizability and chemical compatibility. These parameters are commonly tested
      within a qualification phase, which ensures that an optimal filter design and
      combination finds its use. If such design investigations are neglected it could
      be costly in the process scale.

PMID- 16570864
TI  - Filter validation.
AB  - Validation of a sterilizing filtration process is critical since it is impossible
      with currently available technology to measure the sterility of each filled
      container; therefore, sterility assurance of the filtered product must be
      achieved through validation of the filtration process. Validating a
      pharmaceutical sterile filtration process involves three things: determining the
      effect of the liquid on the filter, determining the effect of the filter on the
      liquid, and demonstrating that the filter removes all microorganisms from the
      liquid under actual processing conditions.

PMID- 16570865
TI  - Integrity testing.
AB  - To ensure that sterilizing grade filters in aseptic processing worked as
      required, such filters are integrity tested. Integrity tests, like the bubble
      point, diffusive flow or pressure hold test, are non-destructive tests, which are
      correlated to a destructive bacteria challenge test. This correlation verifies
      the integrity test limits the filters have to pass. Integrity tests are required
      by regulatory authorities. The post filtration integrity test is a must, pre
      filtration integrity testing is recommended. The different tests have specific
      limitations therefore there is no overall, best integrity test, which can be
      utilized for every filtration system.

PMID- 16570866
TI  - Serosal membranes (pleura, pericardium, peritoneum). Normal structure,
      development and experimental pathology.
AB  - This monograph offers a comprehensive review of the present knowledge of the
      structure of the serosal coverings of the pleural, pericardial, and peritoneal
      cavities in humans and laboratory animals. The authors provide data from their
      own research--with transmission and scanning electron microscopy--on the
      structure of the main components of the serosal membranes: mesothelial cells,
      underlying basal lamina, and submesothelial connective tissue layer. Two main
      types of mesothelial cells (flat and cubic) are distinguished and their
      distribution on the parietal serosal sheets and on the visceral coverings of
      various organs is described. The openings between mesothelial cells (stomata) and
      their relations with lymphatic lacunae are described thoroughly. Special
      reference is made to the serosal accumulations of lymphoid tissue (milky spots).
      The transcellular and intercellular transport to and from serosal cavities is
      studied by means of horseradish peroxidase tracing experiments. The prenatal and
      postnatal developmental studies are focused on human and rat pleura. The
      alterations of serosal membranes after experimental hemothorax, pneumonectomy,
      and peritonitis caused by Pseudomonas aeruginosa application suggest the
      existence of early, reversible, and late, definite periods.

PMID- 16570867
TI  - Dielectrophoresis of DNA: time- and frequency-dependent collections on
      microelectrodes.
AB  - This paper reports measurements that characterize the collection of DNA onto
      interdigitated microelectrodes by high-frequency dielectrophoresis. Measurements
      of time-dependent collection of 12 kilobase pair plasmid DNA onto microelectrodes
      by dielectrophoresis show significant reduction in the response as the frequency
      increases from 100 kHz to 20 MHz. Collection time profiles are quantitatively
      measured using fluorescence microscopy over the range 100 kHz to 5 MHz and are
      represented in terms of two parameters: the initial dielectrophoretic collection
      rate, and the initial to steady-state collection transition. Measured values for
      both parameters are consistent with trends in the frequency-dependent real part
      of the effective polarizability measured for the same plasmid DNA using
      dielectric spectroscopy. The experimentally measured parameters are qualitatively
      compared with trends predicted by theory that takes into account
      dielectrophoretic particle movement and diffusion. The differences between
      experiment and theory are discussed with suggested improvements to theoretical
      models, for example, including the effects of electrohydrodynamically driven
      fluid motion.

PMID- 16570868
TI  - Nanofabrication of polymer surfaces utilizing colloidal lithography and ion
      etching.
AB  - In this paper, we utilize colloidal lithography based on electrostatic self
      assembly of polystyrene colloidal particles onto a polymer surface as a nanoscale
      mask. The pattern is then transferred to the surface by ion beam etching. Each
      particle acts as an individual mask, resulting in an array of identical
      structure. Ion beam exposure etches away the unmasked surface between the
      particles, so the particle mask pattern can be transferred into the polymer
      surface. This method allows to nanofabricate bulk polymeric surfaces with
      systematic variation in relief, structure sizes, and aspect ratios. It is a fast,
      simple, and reliable method to fabricated different polymeric surfaces even on
      large area samples (> 1 cm2). The structural variation is achieved by use of
      different conditions during the self-assembly of the mask (e.g., different
      particles sizes) or different ion etching conditions during the pattern transfer
      (e.g., ion energy, ion flux, ion incident angle, etching time, gas environment).

PMID- 16570869
TI  - Peptide-directed binding of quantum dots to integrins in human fibroblast.
AB  - There is currently a major international effort aimed at integrating
      semiconductor nanostructures with biological structures. This paper reports the
      use of peptide sequences with certain motifs like artinine-glycine-aspartic acid
      (RGD) and leucine-aspartic acid-valine (LDV) to functionalize zinc sulfide (ZnS)
      capped cadmiun selenide (CdSe) quantum dots, so that the quantum dot-peptide
      complexes selectively bind to integrins on HT1080 human fibrosarcoma cells
      membrane. In this way, an interface between semiconductor nanocrystals and
      subcellular components was achieved, and the distribution pattern of RGD and LDV
      receptors on HT1080 cell membranes is revealed. These findings point the way to
      using a wide class of peptide-functionalized semiconductor quantum dots for the
      study of cellular processes involving integrins.

PMID- 16570870
TI  - The effects of colloidal nanotopography on initial fibroblast adhesion and
      morphology.
AB  - Colloidal lithography offers a simple, inexpensive method of producing irregular
      nanotopographies, a pattern not easily attainable utilizing conventional serial
      writing processes. Colloids with 20- or 50-nm diameter were utilized to produce
      such an irregular topography and were characterized by calculating the percentage
      area coverage of particles. Interparticle and nearest neighbor spacing were also
      assessed for the individual colloids in the pattern. Two-way analysis of variance
      (ANOVA) indicated significant differences between the number of fibroblasts
      adhering to planar, 20-, and 50-nm-diameter colloidal topographies, the number of
      fibroblasts adhering to the substrates at the time intervals studied, namely 20
      min, 1 h, and 3 h and significant interaction between time and topography on
      fibroblast adhesion (P < 0.01). Tukey tests were utilized for sensitive
      identification of the differences between the sample means and compounded ANOVA
      results. Cytoskeletal and general cell morphology were investigated on planar and
      colloidal substrates, and indicated cells in contact with irregular
      nanotopographies exhibit many peripheral protrusions while such protrusions are
      absent in cells on planar control surfaces. These protrusions are rich in
      microtubules on 20-nm-diameter colloidal surfaces while microfilaments are
      prevalent on 50-nm-diameter surfaces. Moreover, by 3 h, cells on the colloidal
      substrates initiate cell-cell adhesions, also absent in controls.

PMID- 16570871
TI  - A mathematical formulation of DNA computation.
AB  - DNA computation is to use DNA molecules for information storing and processing.
      The task is accomplished by encoding and interpreting DNA molecules in suspended
      solutions before and after the complementary binding reactions. DNA computation
      is attractive, due to its fast parallel information processing, remarkable energy
      efficiency, and high storing capacity. Challenges currently faced by DNA
      computation are: 1) lack of theoretical computational models for applications and
      2) high error rate for implementation. This paper attempts to address these
      problems from mathematical modeling and genetic coding aspects. The first part of
      this paper presents a mathematical formulation of DNA computation. The model may
      serve as a theoretical framework for DNA computation. In the second part, a
      genetic code based DNA computation approach is presented to reduce error rate for
      implementation, which has been a major concern for DNA computation. The method
      provides a promising alternative to reduce error rate for DNA computation.

PMID- 16570872
TI  - Computational modeling of a new fluorescent biosensor for caspase proteolytic
      activity improves dynamic range.
AB  - The class of fluorescence resonance energy transfer (FRET) protein biosensors
      that are useful for measuring protease activity is composed of a tandem fusion of
      yellow fluorescent protein (YFP), a cleavage recognition sequence, and cyan
      fluorescent protein (CFP). The dynamic range of these FRET-based protein
      biosensors is often weak, but applications such as high throughput drug screening
      require stronger dynamic ranges. Using the biosensor for the caspase-3 protease
      as an example, here we showed a computational approach to improve the FRET
      dynamic range based on the atomic structure of caspase-3 bound to its inhibitor.
      This result was verified from our experiments where the FRET dynamic range
      improved by at least 60% on average in both in vitro and in vivo contexts. In
      concept, the same strategy can be applied to improve dynamic range of other FRET
      based protein biosensors for protease activity where there exist solved atomic
      structures for protein complexes.

PMID- 16570873
TI  - Rule generation for protein secondary structure prediction with support vector
      machines and decision tree.
AB  - Support vector machines (SVMs) have shown strong generalization ability in a
      number of application areas, including protein structure prediction. However, the
      poor comprehensibility hinders the success of the SVM for protein structure
      prediction. The explanation of how a decision made is important for accepting the
      machine learning technology, especially for applications such as bioinformatics.
      The reasonable interpretation is not only useful to guide the "wet experiments,"
      but also the extracted rules are helpful to integrate computational intelligence
      with symbolic AI systems for advanced deduction. On the other hand, a decision
      tree has good comprehensibility. In this paper, a novel approach to rule
      generation for protein secondary structure prediction by integrating merits of
      both the SVM and decision tree is presented. This approach combines the SVM with
      decision tree into a new algorithm called SVM_ DT, which proceeds in three steps.
      This algorithm first trains an SVM. Then, a new training set is generated through
      careful selection from the output of the SVM. Finally, the obtained training set
      is used to train a decision tree learning system and to extract the corresponding
      rule sets. The results of the experiments of protein secondary structure
      prediction on RS126 data set show that the comprehensibility of SVM_DT is much
      better than that of the SVM. Moreover, the generalization ability of SVM_DT is
      better than that of C4.5 decision trees and is similar to that of the SVM. Hence,
      SVM_DT can be used not only for prediction, but also for guiding biological
      experiments.

PMID- 16570875
TI  - Shaping ethics: youth workers matter.
AB  - The authors propose that youth workers and educators committed to informing and
      shaping the ethical understandings of young people first need to explore and
      become aware of their own ethics. This requires front-line staff and caregivers
      to critically reflect on the impact their day-to-day choices and decisions have
      on youth. Once they become clearer about their own ethics and the consequences of
      their decisions, youth workers are then in a position to promote opportunities
      for youth to make ethical choices. The authors use observations and ideas from
      their experiences with the Minnesota Youth Work Institute. Their overarching aim
      is to promote ethical congruence between what is taught, how it is taught, and
      how it is practiced in daily work with youth.

PMID- 16570874
TI  - The state of the art of nanobioscience in Japan.
AB  - This paper reviews a part of the state of the art of nanobioscience in Japan. The
      importance of combination and integration of interdisciplinary principles is
      emphasized for the development of nanobioscience. Biomagnetics, biomechanics,
      nanomachining, self-replicating cell model, neuronal network, drug delivery
      system, and tissue engineering are discussed.

PMID- 16570876
TI  - Moral voices of politically engaged urban youth.
AB  - The relationship between reflection and action is an enduring question for those
      interested in promoting moral development among young people. Educators struggle
      to find effective methods for helping youth reason carefully about moral problems
      and also to show moral commitment in their everyday lives. One place where
      reflection and action come together is in youth activism, where young people
      engage in social action campaigns to improve their schools and communities. What
      are the moral concerns that urban youth raise when given the opportunity? How do
      these concerns get translated into action? Drawing on original and secondary
      sources, this chapter discusses four social action campaigns organized by youth
      in the San Francisco Bay Area, in which youth combined critical moral judgments
      with social action. The chapter is not an empirical study, but instead an effort
      to bring attention to the moral and ethical perspectives that politically engaged
      youth raise. These social action projects suggest that for youth living in low
      income neighborhoods with limited resources, the capacity for critical moral
      reflection about one's surroundings is an important dimension of healthy
      development. Helping youth assess and transform their local environments
      represents a promising direction for moral education and youth development.

PMID- 16570877
TI  - Capitalizing on the human-animal bond to teach ethics to youth.
AB  - The purpose of this study was to evaluate the effectiveness of a livestock ethics
      curriculum developed for high school students in agricultural education classes.
      The curriculum was developed in response to numerous unethical occurrences at
      major livestock shows in recent years. These have included drug violations,
      physical alteration of animals, and excessive involvement of professional
      livestock handlers. The curriculum was taught to 305 students enrolled in eight
      Indiana high school agriculture programs. Data were collected using a pretest and
      posttest. Eighty-six percent of participants improved their score from the
      pretest to the posttest. Participants increased their awareness and knowledge of
      the overall principles involved in making ethical choices when faced with
      decisions in youth livestock programs. Students improved their understanding of
      the consequences associated with making unethical choices when faced with
      decisions in the youth livestock program. Participants were more likely to make
      an ethical choice when faced with a scenario featuring an ethical dilemma.
      Participants who had previously been enrolled in 4-H, Future Farmers of America,
      or an animal project had higher scores than those who had not been previously
      enrolled, but the amount of change from pre- to posttest was similar for those
      with and without such prior exposure. Future research should examine whether
      mastery of this kind of ethics curriculum will lead to better ethical choices in
      real-life situations.

PMID- 16570878
TI  - Internet lives: social context and moral domain in adolescent development.
AB  - The author examines the thinking and behavior of adolescents within the digital
      world. What does all this instant messaging and blogging outside school hours
      mean? Why do adolescents do it? How much time do they spend doing it? How does it
      shape their social, emotional, and moral development? Bradley describes the
      phenomenon and explores some moral development ramifications of a new context of
      social experience for adolescents. It proposes that the digital world creates its
      own social context, with a different set of social conventions from the adult
      mediated "real" world that adolescents also inhabit. It is a social context that
      most adults are aware of but do not understand. Adolescents' experiences in the
      online world influence their experiences in the face-to-face world and play an
      important role in the development of their social and moral knowledge. This
      chapter places the discussion within the context of literature on youth ethics
      that has been developed based on more traditional settings.

PMID- 16570879
TI  - Toward ethical approaches to the inclusion of peers with disabilities.
AB  - What would it mean for program leaders and caregivers to shape the thinking of
      typically developing youth toward their peers with disabilities in a way that we
      could regard as ethically sound? The author weaves examples from his research in
      settings such as Girl Scout troops and Boys and Girls Clubs as well as his own
      parenting experiences to answer this question. He has found that it is
      commonplace for program leaders, coaches, and others to avoid direct discussion
      or acknowledgment of the disabilities of children in their groups, in the
      mistaken belief that this is the best way to demonstrate that all children are
      equal and to avoid the perception of discrimination. His interpretation is that
      this is not a product of thoughtlessness but of caring staff and volunteers who
      believe they are doing the right thing--the ethical thing--by avoiding
      acknowledgment of individual differences. Disabilities--even when they are
      readily apparent--are treated as if they were invisible. Rather than giving
      disabilities the "silent treatment," the author challenges us to go beyond the
      prevailing ethos and find ways to build on naturally occurring opportunities to
      learn more about individual needs and supports.

PMID- 16570880
TI  - "I like to treat others as others would treat me": the development of prosocial
      selves in an urban youth organization.
AB  - The development of moral identity is linked to a sense of self that is prosocial
      and connected to others. Youth organizations, if designed appropriately, may
      provide a setting for social interactions and relationships in which youth can
      enact and receive validation for moral behaviors and develop prosocial selves.
      This chapter reports on findings from a four-year study of identity construction
      within an urban Boys and Girls Club. The author conducted interviews and
      photography projects with seventeen youth ages twelve to eighteen, all of whom
      were active club members. Over half described their race or ethnicity as black or
      African American, while others were Hispanic, Afro-Latino, white, or other. All
      of them either lived in the housing project near the club or had close ties to
      it. Both boys and girls describe themselves as rooted in a rich relational milieu
      that promoted prosocial identities. The importance of respect emerged as a key
      theme in the teens' narratives about themselves and their activities. The author
      found that the club served as a site for the development of prosocial traits in
      an environment characterized by respectful and supportive relationships.

PMID- 16570881
TI  - Promoting children's ethical development through social and emotional learning.
AB  - In today's climate of increased emphasis on measuring achievement through high
      stakes testing, academic subjects are too often divorced from the social context
      in which they are taught. We know that learning is a social process. In fact,
      many educators and other youth development practitioners recognize that social,
      emotional, and ethical development cannot be ignored in the name of better
      academic preparation, especially in the face of data showing that students are
      more disengaged than ever before. Social and emotional learning (SEL) offers
      educators and other youth development personnel a framework for addressing
      students' social and emotional needs in systematic way. SEL is the process of
      acquiring the skills to recognize and manage emotions, develop caring and concern
      for others, establish positive relationships, make responsible decisions, and
      handle challenging situations effectively. Research has shown that SEL has an
      impact on every aspect of children's development: their health, ethical
      development, citizenship, academic learning, and motivation to achieve. This
      chapter profiles one school in Illinois that has been implementing SEL
      programming for a number of years. The authors provide evidence of the impact of
      SEL on school climate, student behavior, and attitudes. Ultimately the authors
      see this as fostering the kind of understanding of the larger world that leads
      young people to make ethical choices. They propose that the lessons learned are
      applicable to a wide variety of settings, including other schools, after-school
      programs, and summer camps.

PMID- 16570883
TI  - Developing a game plan for good sportsmanship.
AB  - It is widely believed in the United States that competition is beneficial for
      youngsters. However, the media are full of examples of players, fans, and coaches
      whose behavior veers out of control. There have been well-documented examples of
      youth in livestock competitions illegally medicating show animals to make them
      appear calmer, officials biasing their rulings toward a team that will take the
      most fans to a playoff game, and team rivalries that have become so caustic as to
      be dangerous for competitors and fans. A university extension and its partners
      created a program called "Great Fans. Great Sports." in order to teach the kinds
      of behaviors we wish to instill among all who are involved in competitions. It
      requires entire communities to develop and implement plans for enhancing
      sportsmanship in music, debate, drama, 4-H, and other arenas, as well as sports.
      The goal is to make good sportsmanship not the exception but the norm. The
      authors provide anecdotal evidence that "Great Fans. Great Sports." is having a
      positive impact on the attitudes and behaviors of competitors, fans, and
      communities.

PMID- 16570882
TI  - Giving youth the social and emotional skills to succeed.
AB  - WINGS for Kids is a nonprofit organization based in Charleston, South Carolina,
      that aims to supply the social and emotional learning (SEL) component into
      existing programs for school-aged children and thereby assist them to recognize
      and manage emotions, care about others, make good decisions, behave ethically and
      responsibly, build satisfying relationships, and avoid negative behaviors. The
      author, who is the founder and CEO of WINGS, traces the ethos of the organization
      to her own life experiences as well as her observations of low-income children
      and families more generally. She describes the strategies and practices that
      characterize the WINGS approach to SEL. The chapter focuses on the progress made
      by one boy, who arrived at WINGS at the age of seven, got into disputes from the
      very first day, and was eventually ejected from the WINGS program but later
      earned his way back with a commitment to change. He sustained his involvement for
      a number of years and became an exemplar of what the author states they are
      trying to accomplish.

PMID- 16570884
TI  - Pathways of influence in out-of-school time: a community-university partnership
      to develop ethics.
AB  - If we wish to incorporate parents and community members as full partners in
      building character among youth, then the activities and programs in which youth
      participate during their out-of-school time are potentially important venues.
      This chapter describes how numerous agencies in a single community partnered with
      a university, with the help of the cooperative extension agent, to collect local
      data on how adolescents used out-of-school time, what they thought about right
      and wrong, and how well their own behavior comported with their understandings of
      what was right. Results indicated that surveyed youth characterized themselves as
      thinking more than acting in ethical ways. For instance, nearly half acknowledged
      having cheated on a test at least once in the past six months, although the vast
      majority thought that cheating was wrong. The three pathways the community
      identified for reaching youth were (1) extracurricular activities at school such
      as sports, yearbook, and pep club; (2) organized nonschool pursuits such as
      music, dance, hiking, and biking; and (3) religious activities. They found that
      nearly 90 percent of high school-aged respondents participated in one or another
      of these venues.

PMID- 16570885
TI  - Blood management.

PMID- 16570886
TI  - Presentation and management of arthritis affecting the trapezio-metacarpal joint.
AB  - Arthritis affecting the trapezio-metacarpal joint (TMJ) of the thumb is a very
      common condition, and in the upper limb represents the site most often requiring
      surgery for symptomatic osteoarthritis. The condition predominantly affects
      women, especially those who are post menopausal. Management of the condition
      initially entails the use of conservative measures. Many of these are
      administered in the community by general practitioners as well as occupational
      therapists, surgery being reserved for disabling symptoms and loss of function
      resistant to these measures. From a review of the currently available literature,
      we present an overview of this common condition, commenting on its clinical
      presentation, pathophysiology and the treatment options available. A treatment
      algorithm is presented, to aid practitioners in the management and referral of
      patients with symptomatic thumb TMJ arthritis.

PMID- 16570887
TI  - The role of postoperative blood recovery for patients with femoral neck fracture.
AB  - Postoperative blood recovery in eighty elderly patients (11 male, 69 female)
      treated for femoral neck fracture was prospectively studied. Twenty-eight
      patients underwent hemiarthroplasty for intracapusular fracture and 52 underwent
      Dynamic Hip Screw fixation for extracapsular femoral neck fracture. The mean
      blood drainage in the postoperative period and the mean drop in haemoglobin level
      was higher in the DHS group as compared to the hemiarthroplasty group. Mean
      drainage in the first 6 postoperative hours was 150 ml (range: 10-450 ml) in the
      DHS group, versus 50 ml in the hemiarthroplasty group (range: 10-100 ml). Out of
      52 cases of the dynamic hip screw fixation group, only 10 patients received
      autologous blood transfusion (19%), among which the drains collected more than
      150 ml in only 4 (7%). The blood drainage in this group occurred in the first 6
      hours only. Supplementary cross matched bank blood was transfused to patients in
      the DHS group (8%). Among 28 patients in the hemiarthroplasty group, only 6
      patients received autologous blood reperfusion (21%), among which the drains
      collected more than 150 ml in only 4 (14%). Overall, only six patients out of 28
      in the hemiarthroplasty and 10 out 52 in the DHS group had enough blood in their
      drains to warrant re-perfusion. We conclude that the routine use of Bellovac
      drains after femoral neck fracture surgery is not necessary and is not cost
      effective.

PMID- 16570888
TI  - Autologous blood transfusion after primary unilateral total knee replacement
      surgery.
AB  - A prospective study was undertaken to assess the efficacy and financial cost of
      the use of an autologous blood transfusion device in the reduction of allogeneic
      blood requirements of patients undergoing primary unilateral total knee
      arthroplasty. Forty-nine consecutive patients received either the CellTrans blood
      salvage device (group A of 32 patients) or the Redivac high vacuum drainage
      system (group B of 17 patients). The preoperative and postoperative haemoglobin
      levels were recorded at 72 or 96 hours. Nine percent of group A patients received
      an allogeneic blood transfusion compared to 59% in group B. There was an average
      saving of 1.1 unit of allogeneic blood per patient in group A (p<0.001). The
      total cost per patient was about Euro 111 less for the group A patients.
      Autologous re-infusion was found in this study to be an effective method of
      reducing allogeneic blood requirements and to afford significant cost savings in
      primary unilateral knee arthroplasty.

PMID- 16570889
TI  - Postoperative re-perfusion of drained blood in patients undergoing total knee
      arthroplasty: is it effective and cost-efficient?
AB  - The value of postoperative salvage and re-infusion of drained blood was assessed
      in 155 patients undergoing total knee arthroplasty for primary knee
      osteoarthritis. In group A (n = 77), standard vacuum drains were used. In group B
      (n = 78), an auto-transfusion system was used and the blood drained within 6
      hours postoperatively was re-infused. Group B patients were further distributed
      into 2 subgroups, in one of which methylprednisolone was administered before
      blood re-perfusion. Patients who received autologous blood had higher levels of
      haemoglobin at 8 hours (p < 0.05) and 24 hours postoperatively (p < 0.01) and
      needed less allogeneic blood transfusion (p < 0.01). Methylprednisolone
      administration was found to attenuate the postoperative febrile reaction (p =
      0.01).

PMID- 16570890
TI  - A prospective audit of blood usage post primary total knee arthroplasty.
AB  - The use of allogeneic blood is associated with many complications. A baseline
      audit performed in our institution in 2000 showed that 11% of patients undergoing
      primary total knee arthroplasty (TKA) required post-operative transfusion.
      Following this audit, patients undergoing primary TKA were no longer routinely
      cross matched, a Haemovigilance Nurse was employed in compliance with the
      National Blood Users Group guidelines, and post-operative cell salvage was
      introduced for patients with a preoperative haemoglobin level of less than 12
      g/dl. A prospective audit was then performed over a nine month period, from 1st
      January to 30th September 2003, to assess the impact of these changes on our
      transfusion practice. Data was collected on 233 patients who had primary TKA
      performed during the period of our prospective audit. Patients were transfused if
      their blood loss exceeded a pre-calculated maximal allowable loss, or based on a
      48 hour post-operative haemoglobin level. Seventeen of the 233 patients (7 %)
      received allogeneic blood. The average amount received was two units. Pre
      operative anaemia and advanced patient age were predictive for increased risk of
      transfusion. Thirty six per cent of patients who were given a cell saver did not
      collect sufficient blood for re-transfusion. Ten per cent required further
      transfusion with allogeneic blood. There was no statistically significant
      difference in either the percentage of patients transfused or the volume of blood
      given to each patient between the two periods of audit. We did not find post
      operative cell salvage to be an effective method of reducing allogeneic blood
      use.

PMID- 16570891
TI  - The association between aspirin and blood loss in hip fracture patients.
AB  - This is a cohort study involving 98 patients who presented to a regional
      orthopaedic unit with a hip fracture. Blood loss was assessed by pre and post
      operative haemoglobin concentrations, and transfusion requirements were used as
      outcome measures. The influence of pre-operative aspirin use and fracture type
      was analysed with respect to these outcome measures. Forty two percent of
      patients were regular aspirin users, and were comparable to the non aspirin
      group, apart from having a significantly greater prevalence of atherosclerotic
      vascular disease. There was no significant difference between the aspirin and non
      aspirin groups in terms of preoperative haemoglobin concentrations, perioperative
      changes in haemoglobin levels and transfusion requirements. Fifty one percent of
      patients had extracapsular hip fractures, and these patients were comparable in
      terms of demographic characteristics, including aspirin use, to the group with
      intracapsular hip fractures. The extracapsular hip fracture group were found to
      have significantly increased peri-operative blood loss as measured by changes in
      the haemoglobin level, and in transfusion requirements when analysed against the
      intracapsular hip fracture group. We found that it is the fracture site, rather
      than aspirin use pre-operatively, that is predictive of blood loss and
      transfusion requirements in patients presenting with hip fractures.

PMID- 16570892
TI  - Delayed release of drain in total knee replacement reduces blood loss. A
      prospective randomised study.
AB  - Total knee arthroplasty is sometimes associated with major post-operative
      bleeding, often requiring transfusion. A prospective, randomised study was
      undertaken to assess the effect on post-operative bleeding of delaying release of
      the clamp on the suction drains. One hundred patients were allocated into two
      groups: Group A- immediate release of drain following release of tourniquet, and
      Group B- delayed release of the drain clamp by one hour. There was a
      statistically significant reduction (p = < 0.001) in postoperative bleeding
      between group A (1050 ml; 95%CI 728 - 1172 ml) compared to group B (732 ml; 95%
      CI 620- 845 ml). Average drop in corrected haemoglobin and postoperative
      transfusion requirement were also less in the delayed group. The results show
      that delaying release of the drains by one hour reduces postoperative blood loss
      and transfusion requirement following total knee arthroplasty.

PMID- 16570893
TI  - External fixation of femoral fractures in multiply injured intensive care unit
      patients.
AB  - We report the results of a prospective study of 42 patients with multiple
      injuries, including femoral fractures, who required intensive care unit (ICU)
      admission and whose fractures were treated by means of external fixation. The
      Injury Severity Score (ISS) ranged from 18 to 41 and the average Glasgow Coma
      Scale (GCS) on admission was 12. Seventeen fractures were open. All patients had
      their fractures stabilised within 6 hours from admission by means of external
      fixation. After a follow-up of 11 months (range 4-20), 28 fractures had healed
      within 6 months (range 4.5-8) and 13 developed non-union which was treated
      successfully with secondary intramedullary nailing. One patient developed deep
      infection following secondary nailing and another patient died from adult
      respiratory distress syndrome (ARDS). We conclude that external fixation of
      severe femoral fractures in critically ill patients is an easy and quick method
      of stabilisation which does not compromise their condition. If however it is
      intended to be used as a final method, these patients require a close follow-up
      since the rate of delayed and non-union is high.

PMID- 16570894
TI  - Effect of risedronate on bone metabolism after total hip arthroplasty: a
      prospective randomised study.
AB  - Aseptic loosening due to bone remodeling and osteolysis is the main reason for
      revision hip arthroplasty. At present, there is no established prophylaxis for
      this complication. On the other hand, it has been demonstrated that
      bisphosphonates prevent bone loss around total hip arthroplasties (THA). The aim
      of this study was to assess the efficacy of oral bisphosphonate risedronate for
      the prevention of deleterious changes in bone metabolism after hip replacement.
      Twenty-four patients who underwent THA were randomised to two treatment arms: 35
      mg risedronate once weekly for 6 months (12 patients) and no treatment for
      controls (12 patients). Markers of bone turnover bone specific alkaline
      phosphatase, serum osteocalcin and urinary deoxypiridinoline were evaluated at
      baseline, third and sixth postoperative month. Dual energy X-ray absorptiometry
      of the nonsurgical hip was performed preoperatively and at 6 months
      postoperatively. There were no significant differences in clinical or
      radiographic findings between the two groups at either 3 or 6 months. In the two
      groups, all biochemical marker responses at the third postoperative month were
      suppressed compared with baseline. Values of bone resorption marker urinary
      deoxypiridinoline increased significantly at six months in the control group. For
      the 10 risedronate patients with bone densitometry bone mineral density reached
      1.01% increase at 6 months. Administration of oral risedronate led to a
      significant reduction in bone metabolism at 6 months after hip replacement. This
      therapeutic strategy may improve the results and longevity of total hip
      arthroplasty. The beneficial effect of risedronate should be confirmed in further
      studies including larger number of patients and longer follow-up. The action of
      risedronate could prevent aseptic loosening of hip arthroplasty by preserving
      periprosthetic bone stock.

PMID- 16570895
TI  - Proximal femoral geometry and hip fractures.
AB  - There is increasing evidence that proximal femoral geometry has an important role
      in the aetiology of hip fractures. We performed a simple radiological study to
      investigate the relationship between proximal femoral geometry and intracapsular
      and extracapsular fractures of the proximal femur. Measurements of proximal
      femoral geometry were made on pelvic radiographs on the contralateral hip of 50
      consecutive patients with intracapsular and 50 with extracapsular fractures. The
      groups were matched for age and sex with a mean age of 79 and a female :male
      ratio of 4 :1. There were no statistical differences in head diameter, neck width
      or Head Trochanter Length between the two groups of fractures. Hip Axis Length,
      neck length and the neck length :width ratio were significantly greater in the
      intracapsular group, suggesting an aetiological link. This may have implications
      for future screening and prevention of proximal hip fractures, particularly
      intracapsular fractures.

PMID- 16570896
TI  - The uncemented isoelastic/isotitan total hip arthroplasty. A 10-15 years follow
      up with bone mineral density evaluation.
AB  - The present study analyses the long-term outcome of isoelastic hip prostheses and
      their influence on the extent of periprosthetic bone remodeling. Ninety-two
      patients (102 hips) with Isoelastic/Isotitan uncemented total hip arthroplasty
      were evaluated after an average of 13.4 years. The average age of patients at
      surgery was 42.5 years. The clinical outcome was assessed based on the Harris hip
      score, complications and thigh pain. Bone mineral density (BMD) of the proximal
      femur in the seven Gruen zones was evaluated by dual-energy X-ray absorptiometry
      (DEXA) scans with the contralateral hip serving as a control. The average Harris
      hip score at the most recent follow-up was 72 points, with 72 hips (70%) rating
      completely pain free. Eight stems required revision whereas none of the cups
      showed any evidence of loosening. The change in the mean BMD values between the
      femora on the operated side and the contralateral femora averaged 15% for all
      zones Although the isoelastic stems are no longer used owing to their high
      loosening rate, it appears that this prosthesis preserved periprosthetic bone
      better than reported for cemented or uncemented metallic implants. Besides, the
      provision of a titanium coating on the isoelastic stem, comparable to that on the
      RM cup, would presumably have improved its long-term fixation by encouraging bony
      ongrowth.

PMID- 16570897
TI  - Clinical results of isolated reconstruction of the medial patellofemoral ligament
      for recurrent dislocation and subluxation of the patella.
AB  - Complications and results of medial patellofemoral ligament (MPFL)
      reconstruction, performed between 2000 and 2003, were studied retrospectively in
      24 randomised patients (24 knees). All procedures were performed for recurrent
      dislocation or subluxation of the patella, using an autogenous semitendinosus
      tendon. Two different methods of anchoring of the transplant were compared. After
      a 2-year follow-up, patellar stability was found to be similar, when the
      transplant was sutured to the fibrous tissue and periosteum overlying the patella
      or when it was fixed in a bone tunnel through the patella. The majority of the
      patients who had undergone MPFL reconstruction have returned to their previous
      level of sports activities. We had two cases of patella fracture and one case of
      persisting patella apprehension after surgery. Further studies must determine
      which measures are necessary to prevent these complications.

PMID- 16570898
TI  - Ultrasound assessment of internal derangement of the knee.
AB  - In a prospective double-blind study we investigated internal knee disorders with
      ultrasound and compared the results with Magnetic Resonance Imaging (MRI) and
      arthroscopy. The aim was to determine the effectiveness of ultrasound in
      diagnosing Internal Derangement of the Knee (IDK) and to compare the results with
      MRI. Over an 18-months period, 81 patients were examined. All were male; they had
      a mean age of 35 years. For various technical reasons 21 patients were
      subsequently excluded from the study. After initial clinical examinations,
      patients had an ultrasound and MRI scan at the same visit. Arthroscopy was
      performed within a month of this. Different radiologists who were unaware of the
      clinical findings independently reported on the ultrasound and MRI. The surgeon
      performing the arthroscopy was made aware only of the MRI findings. Structures
      accessed were the lateral and medial menisci and the anterior (ACL) and posterior
      (PCL) cruciate ligaments. Arthroscopy was taken as the gold standard. Ultrasound
      showed good sensitivity, ranging from 76% for the ACL to 90% for the medial
      meniscus, and excellent specificity, ranging from 92% for the medial meniscus to
      100% for the ACL. Accuracy ranged from 86% for the ACL to 98% for the lateral
      meniscus. These figures were comparable to the MRI findings. We concluded that
      ultrasound is a simple, accurate, inexpensive and non-invasive way of assessing
      internal knee disorders. There is a learning curve, but results are similar to
      MRI.

PMID- 16570899
TI  - Focal fibrocartilaginous dysplasia of the tibia: long-term evolution.
AB  - Focal fibrocartilaginous dysplasia of the tibia (FFCD) is a rare and benign
      condition associated with unilateral tibia vara in childhood. The first
      description was done by Bell in 1985. Since then more than sixty cases have been
      reported. The aetiology remains unknown. Five new cases are retrospectively
      reported. Four of them with tibia vara less than 30 degrees showed a spontaneous
      correction. One patient had a severe varus deformity (> 30 degrees) leading to
      physeal impairment and underwent a tibial valgus osteotomy. Biopsy is not
      necessary as radiographs are typical. The infantile growth plate is able to
      correct a tibia vara due to FFCD if less than 30 degrees. In case of spontaneous
      resolution, a long-term follow-up remains necessary because of a possible
      progressive leg length discrepancy.

PMID- 16570900
TI  - Intervertebral prosthesis versus anterior lumbar interbody fusion: one-year
      results of a prospective non-randomised study.
AB  - The authors conducted a prospective non-randomised study on the ProDisc
      intervertebral prosthesis versus anterior lumbar interbody fusion (ALIF). The
      first group included 14 patients, the second group 10 patients. In the ProDisc
      group the Oswestry Disability Index improved from +/- 38.42 preoperatively (60
      being the worst possible condition) to +/- 15.21 after 6 months and to +/- 12.5
      after 12 months. This was definitely better than the ALIF group, where the
      corresponding figures were +/- 38, +/- 25 and +/- 21.4. The ProDisc patients also
      scored better with respect to duration of hospitalisation, blood loss and
      operation time. The complications were comparable in both groups.

PMID- 16570901
TI  - Single side hole irrigation--a simple method of catheter irrigation of the tendon
      sheath.
AB  - Treatment of septic flexor tenosynovitis at the hand requires significant
      hospital resources in terms of operative time and subsequent management of tendon
      irrigation. Delayed recovery or treatment failure may require re-irrigation and
      drainage. This may be due to failure to adequately irrigate the entire flexor
      sheath. We describe a method of closed tendon sheath irrigation which is simple
      to use and ensures that the complete tendon sheath is adequately irrigated.
      Unwieldy continuous irrigation is avoided and patient inconvenience is kept to a
      minimum.

PMID- 16570902
TI  - Coracoclavicular joint degeneration, an unusual cause of painful shoulder: a case
      report.
AB  - A case of painful shoulder in a 42-year old right-hand dominant Caucasian female
      due to degeneration of the coracoclavicular joint is described. The pain was
      aggravated by weight lifting. The diagnosis was confirmed radiographically with
      simple plain films and clinically by the injection of local anaesthetic
      (xylocaine 2%) that lead to the exclusion of any other concomitant pathology of
      the acromioclavicular joint and the anterior subacromial space. The patient was
      treated successfully with an intraarticular steroid injection, and 30 months
      later she remains free of symptoms.

PMID- 16570904
TI  - Iatrogenic blunt arterial injury during a hip fracture surgery.
AB  - Iatrogenic non-penetrating arterial injuries have been reported following primary
      and revision hip arthroplasties. We report a patient who developed acute limb
      ischaemia after dynamic hip screw fixation was performed for an unstable
      intertrochanteric fracture. We discuss a previously unreported mechanism of
      traction creating tension on the atherosclerosed vessels and medial retraction
      tenting and breaking the vessel wall lining. This case highlights a serious
      complication in one of the most commonly performed hip surgeries.

PMID- 16570903
TI  - Complex dorsal subluxation of the metacarpo-phalangeal joint of the thumb
      requiring open reduction: a case report.
AB  - The authors present an case of a thumb metacarpophalangeal joint dislocation
      which was made complicated by the interposition of the sesamoid bone which
      required open reduction. The intact volar plate prevented closed reduction. The
      anatomy and surgical management of this unusual case is described.

PMID- 16570905
TI  - Fibromyxoma of bone: a case report and review of the literature.
AB  - In this study, a case of fibromyxoma of the proximal femur in a 59-year old woman
      is reported. The classification of this rare bone tumour is still a matter of
      debate and some investigators have suggested that these lesions represent a
      degenerative form of fibrous dysplasia. Some authors make a further distinction
      between fibromyxoma and myxoma of bone. In a review of 23 cases of fibromyxoma
      and five cases of myxoma, no differences in clinical, radiographic and biologic
      behaviour between fibromyxoma and myxoma were found. Apart from the age at
      diagnosis, the most important difference between fibromyxoma and myxoma was the
      degree of myxoid matrix. Therefore, we suggest that extragnathic myxoma is a
      regressive variant of extragnathic fibromyxoma and should be termed as the same
      entity. In contrast to monostotic fibrous dysplasia fibromyxoma / myxoma often
      causes pain and presents as a Lodwick IC lesion with a soft tissue mass.
      Therefore, fibromyxoma / myxoma should be distinguished from fibrous dysplasia
      because of its different clinical and radiographic features.

PMID- 16570906
TI  - Rupture of the tibialis anterior tendon.
AB  - Rupture of the tibialis anterior tendon is rare. There is usually a delay in
      diagnosis, probably because it is an uncommon entity. Diagnosis is easy however,
      and recovery with surgical treatment is satisfactory if repair is performed
      within the first three months following the initial trauma. After this period of
      time, an operation is less likely to be effective. We report a case with
      successful outcome following surgical repair of a ruptured tibialis anterior
      tendon.

PMID- 16570907
TI  - Osteosarcoma of the talus: a case report.
AB  - The reported incidence of osteosarcoma of the foot is very low. Osteosarcoma of
      the talus is extremely rare and few cases have been reported in the literature.
      The clinical findings are not typical, and osteosarcoma of the talus can be
      easily misdiagnosed, resulting in a delay in proper treatment. We report the case
      of a patient with osteosarcoma of the talus, from a series of 120 osteosarcomas
      treated at our hospital between 1966 and 2002.

PMID- 16570908
TI  - Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5
      yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215),
      an in vivo active potent VEGFR-2 inhibitor.
AB  - A series of substituted 4-(4-fluoro-1H-indol-5-yloxy)pyrrolo[2,1
      f][1,2,4]triazine-based inhibitors of vascular endothelial growth factor receptor
      2 kinase is reported. Structure-activity relationship studies revealed that a
      methyl group at the 5-position and a substituted alkoxy group at the 6-position
      of the pyrrolo[2,1-f][1,2,4]triazine core gave potent compounds. Biochemical
      potency, kinase selectivity, and pharmacokinetics of the series were optimized
      and in vitro safety liabilities were minimized to afford BMS-540215 (12), which
      demonstrated robust preclinical in vivo activity in human tumor xenograft models.
      The l-alanine prodrug of 12, BMS-582664 (21), is currently under evaluation in
      clinical trials for the treatment of solid tumors.

PMID- 16570909
TI  - Nanomolar inhibitors of the peptidyl prolyl cis/trans isomerase Pin1 from
      combinatorial peptide libraries.
AB  - The peptidyl prolyl cis/trans isomerase Pin1 has been implicated in the
      development of cancer, Alzheimer's disease and asthma, but highly specific and
      potent Pin1 inhibitors remain to be identified. Here, by screening a
      combinatorial peptide library, we identified a series of nanomolar peptidic
      inhibitors. Nonproteinogenic amino acids, incorporated into 5-mer to 8-mer
      oligopeptides containing a d-phosphothreonine as a central template, yielded
      selective inhibitors that blocked cell cycle progression in HeLa cells in a dose
      dependent manner.

PMID- 16570910
TI  - Synergy and antagonism of promiscuous inhibition in multiple-compound mixtures.
AB  - Screening in mixtures is a common approach for increasing the efficiency of high
      throughput screening. Here we investigate how the "compound load" of mixtures
      influences promiscuous aggregate-based inhibition. We screened 764 molecules
      individually and in mixtures of 10 at 5 miccroM each, comparing the observed
      inhibition of the mixtures to that predicted from single-compound results.
      Synergistic effects on aggregation predominated, although antagonism was also
      observed. These results suggest that screening mixtures can increase aggregation
      based inhibition in a nonadditive manner.

PMID- 16570911
TI  - Synthesis and structure-activity relationship effects on the tumor avidity of
      radioiodinated phospholipid ether analogues.
AB  - Radioiodinated phospholipid ether analogues have shown a remarkable ability to
      selectively accumulate in a variety of human and animal tumors in xenograft and
      spontaneous tumor rodent models. It is believed that this tumor avidity arises as
      a consequence of metabolic differences between tumor and corresponding normal
      tissues. The results of this study indicate that one factor in the tumor
      retention of these compounds in tumors is the length of the alkyl chain that
      determines their hydrophobic properties. Decreasing the chain length from C12 to
      C7 resulted in little or no tumor accumulation and rapid clearance of the
      compound in tumor-bearing rats within 24 h of administration. Increasing the
      chain length had the opposite effect, with the C15 and C18 analogues displaying
      delayed plasma clearance and enhanced tumor uptake and retention in tumor-bearing
      rats. Tumor uptake displayed by propanediol analogues NM-412 and NM-413 was
      accompanied by high levels of liver and abdominal radioactivity 24 h
      postinjection to tumor-bearing rats. Addition of a 2-O-methyl moiety to the
      propanediol backbone also retarded tumor uptake significantly. A direct
      comparison between NM-404 and its predecessor, NM-324, in human PC-3 tumor
      bearing immune-compromised mice revealed a dramatic enhancement in both tumor
      uptake and total body elimination of NM-404 relative to NM-324. On the basis of
      imaging and tissue distribution studies in several rodent tumor models, the C18
      analogue, NM-404, was chosen for follow-up evaluation in human lung cancer
      patients. Preliminary results have been extremely promising in that selective
      uptake and retention of the agent in tumors is accompanied by rapid clearance of
      background radioactivity from normal tissues, especially those in the abdomen.
      These results strongly suggest that extension of the human trials to include
      other cancers is warranted, especially when NM-404 is radiolabeled with iodine
      124, a new commercially available positron-emitting isotope. The relatively long
      physical half-life of 4 days afforded by this isotope appears well-suited to the
      pharmacodynamic profile of NM-404.

PMID- 16570912
TI  - Design, synthesis, and biological evaluation of semicarbazide-sensitive amine
      oxidase (SSAO) inhibitors with anti-inflammatory activity.
AB  - In an attempt to examine the effect of inhibition of semicarbazide-sensitive
      amine oxidase (SSAO; EC 1.4.3.6, also known as VAP-1) as a novel anti
      inflammatory target, the structure/mechanism based design and synthesis of a
      series of novel hydrazino-containing small molecules are described. The in vitro
      biological results show that compounds 4a,c are highly potent SSAO inhibitors
      with notable selectivity toward SSAO over monoamine oxidases A and B (MAO-A and
      MAO-B). SAR studies based on compound 4c were performed, and the results are
      discussed. The most potent and selective compound, 4a (IC(50) = 2 nM), is an
      orally active, competitive, and apparently irreversible inhibitor of SSAO that is
      effective at reducing disease incidence and severity in an in vivo animal disease
      model of multiple sclerosis.

PMID- 16570914
TI  - Identification of potent and selective inhibitors of PDGF receptor
      autophosphorylation.
AB  - We report the structure-activity relationship of quinoline and quinazoline
      derivatives, which include urea, thiourea, urethane, and acylthiourea groups, as
      inhibitors of the platelet-derived growth factor (PDGF) receptor
      autophosphorylation. Our previous studies showed that the quinoline and
      quinazoline derivatives including urea, thiourea, and carbamate groups were
      highly potent compounds as the PDGF receptor autophosphorylation inhibitor, but
      these compounds did not exhibit receptor selectivity between the PDGF receptor
      and the c-kit receptor. As a result of further synthesis and biological
      evaluation, we have found that the quinoline and quinazoline-acylthiourea
      derivatives showed not only good inhibitory activity for the PDGF receptor but
      also receptor selectivity between the PDGF receptor and the c-kit receptor.
      Furthermore N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(2
      methylbenzoyl)thiourea exhibited potent oral efficacy in in vivo assay using the
      rat carotid balloon injury model. Therefore, the quinoline and quinazoline
      acylthiourea derivatives may be expected to have potential as therapeutic agents
      for the treatment of restenosis.

PMID- 16570915
TI  - Modeling the peptide-T cell receptor interaction by the comparative molecular
      similarity indices analysis-soft independent modeling of class analogy technique.
AB  - A set of 38 epitopes and 183 non-epitopes, which bind to alleles of the HLA-A3
      supertype, was subjected to a combination of comparative molecular similarity
      indices analysis (CoMSIA) and soft independent modeling of class analogy (SIMCA).
      During the process of T cell recognition, T cell receptors (TCR) interact with
      the central section of the bound nonamer peptide; thus only positions 4-8 were
      considered in the study. The derived model distinguished 82% of the epitopes and
      73% of the non-epitopes after cross-validation in five groups. The overall
      preference from the model is for polar amino acids with high electron density and
      the ability to form hydrogen bonds. These so-called "aggressive" amino acids are
      flanked by small-sized residues, which enable such residues to protrude from the
      binding cleft and take an active role in TCR-mediated T cell recognition.
      Combinations of "aggressive" and "passive" amino acids in the middle part of
      epitopes constitute a putative TCR binding motif.

PMID- 16570913
TI  - Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)-
      and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine.
AB  - A new enantiomeric synthesis utilizing classical resolution provided two novel
      series of optically active inhibitors of cholinesterase: (-)- and (+)-O-carbamoyl
      phenols of tetrahydrofurobenzofuran and methanobenzodioxepine. An additional two
      series of (-)- and (+)-O-carbamoyl phenols of pyrroloindole and furoindole were
      obtained by known procedures, and their anticholinesterase actions were similarly
      quantified against freshly prepared human acetyl- (AChE) and
      butyrylcholinesterase (BChE). Both enantiomeric forms of each series demonstrated
      potent cholinesterase inhibitory activity (with IC(50) values as low as 10 nM for
      AChE and 3 nM for BChE), with the exception of the (+)-O-carbamoyl phenols of
      pyrroloindole, which lacked activity (IC(50) values >1 microM). Based on the
      biological data of these four series, a structure-activity relationship (SAR)
      analysis was provided by molecular volume calculations. In addition, a probable
      transition-state model was established according to the known X-ray structure of
      a transition-state complex of Torpedo californica AChE-m-(N,N,N-trimethylammonio)
      2,2,2-trifluoroacetophenone (TcAChE-TMTFA). This model proved valuable in
      explaining the enantioselectivity and enzyme subtype selectivity of each series.
      These carbamates are more potent than, or similarly potent to,
      anticholinesterases in current clinical use, providing not only inhibitors of
      potential clinical relevance but also pharmacological tools to define drug-enzyme
      binding interactions within an enzyme crucial in the maintenance of cognition and
      numerous systemic physiological functions in health, aging, and disease.

PMID- 16570916
TI  - Stereospecific synthesis of a carbene-generating angiotensin II analogue for
      comparative photoaffinity labeling: improved incorporation and absence of
      methionine selectivity.
AB  - A stereospecific convergent synthesis of N-[(9-fluorenyl)methoxycarbonyl]-p-[3
      (trifluoromethyl)-3H-diazirin-3-yl]-l-phenylalanine (Fmoc-12, Fmoc-Tdf) and its
      incorporation into the C-terminal position of the angiotensin II (AngII) peptide
      to form (125)I[Sar(1),Tdf(8)]AngII ((125)I-13) is presented. This amino acid
      photoprobe is a highly reactive carbene-generating diazirine phenylalanine
      derivative that can be used for photoaffinity labeling. Using model receptors, we
      compared the reactivity and the Met selectivity of 12 to that of the widely used
      and reputedly Met-selective p-benzoyl-l-phenylalanine (Bpa) photoprobe. Wild-type
      and mutant AngII type 2 receptors, a G protein-coupled receptors, were
      photolabeled with (125)I-13 as well as with (125)I[Sar(1),Bpa(8)]AngII ((125)I
      14), and the respective incorporation yields were assessed. The carbene
      generating 12 was more reactive toward inert residues and was not Met-selective
      compared to the biradical ketone-generating Bpa, allowing for more precise
      determination of ligand contact points in peptidergic receptors.

PMID- 16570917
TI  - Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro
      2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orally active
      transforming growth factor-beta type I receptor inhibitor.
AB  - Inhibitors of transforming growth factor beta (TGF-beta) type I receptor (ALK5)
      offer a novel approach for the treatment of fibrotic diseases such as renal,
      hepatic, and pulmonary fibrosis. The optimization of a novel phenylpyridine
      pyrazole series (1a) led to the identification of potent, selective, and orally
      active ALK5 inhibitors. The cellular potency and pharmacokinetics profiles of
      these derivatives were improved and several compounds presented antifibrotic
      activity when orally administered to rats in an acute liver model of
      dimethylnitrosamine- (DMN-) induced expression of collagen IA1 mRNA, a major gene
      contributing to excessive extra cellular matrix deposit. One of the most potent
      ALK5 inhibitors identified in this chemical series, compound 13d (GW788388),
      reduced the expression of collagen IA1 by 80% at a dose of 1 mg/kg twice a day
      (b.i.d.). This compound significantly reduced the expression of collagen IA1 mRNA
      when administered orally at 10 mg/kg once a day (u.i.d.) in a model of puromycin
      aminonucleoside-induced renal fibrosis.

PMID- 16570918
TI  - Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and
      indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for
      the treatment of congestive heart failure and myocardial fibrosis.
AB  - In this study, the synthesis and biological evaluation of heteroaryl-substituted
      dihydronaphthalenes and indenes (1-16) is described. The compounds were tested
      for activity by use of human CYP11B2 expressed in fission yeast and V79 MZh cells
      and for selectivity by use of human CYP11B1, CYP17, and CYP19. The most active
      inhibitor was the 6-methoxydihydronaphthalene 4 (IC(50) = 2 nM), showing a K(i)
      value of 1.3 nM and a competitive type of inhibition. The 5-methoxyindene 3 was
      found to be the most selective CYP11B2 inhibitor (IC(50) = 4 nM; CYP11B1 IC(50) =
      5684 nM), which also showed only marginal inhibition of human CYP3A4 and CYP2D6.
      Docking and molecular dynamics studies using our homology-modeled CYP11B2
      structure were performed to understand some structure-activity relationships.
      Caco-2 cell experiments revealed highly cell-permeable compounds, and metabolic
      studies with 4 using rat liver microsomes showed sufficient stability.

PMID- 16570919
TI  - Novel potent and efficacious nonpeptidic urotensin II receptor agonists.
AB  - Six different series of nonpeptidic urotensin II receptor agonists have been
      synthesized and evaluated for their agonistic activity in a cell-based assay (R
      SAT). The compounds are ring-opened analogues of the isochromanone-based agonist
      AC-7954 with different functionalities constituting the linker between the two
      aromatic ring moieties. Several of the compounds are highly potent and
      efficacious, with N-[1-(4-chlorophenyl)-3-(dimethylamino)-propyl]-4
      phenylbenzamide oxalate (5d) being the most potent. The pure enantiomers of 5d
      were obtained from the corresponding diastereomeric amides. It was shown by a
      combination of X-ray crystallography and chemical correlation that the activity
      resides in the S-enantiomer of 5d (pEC(50) 7.49).

PMID- 16570920
TI  - Development of a structural model for NF-kappaB inhibition of sesquiterpene
      lactones using self-organizing neural networks.
AB  - A variety of sesquiterpene lactones (SLs) possess considerable anti-inflammatory
      activity. Several studies have shown that they exert this effect in part by
      inhibiting the activation of the transcription factor NF-kappaB. In the present
      study we elaborated on the investigation of a data set of 103 structurally
      diverse SLs for which we had previously developed several different QSAR
      equations dependent on the skeletal type. Use of 3D structure descriptors
      resulted in a single model for the entire data set. In particular, local radial
      distribution functions (L-RDF) were used that centered on the methylene-carbonyl
      substructure believed to be the site of attack of cysteine-38 of the p65/NF
      kappaB subunit. The model was developed by using a counterpropagation neural
      network (CPGNN), attesting to the power of this method for establishing structure
      activity-relationships. The investigations shed more light onto the influence of
      the chemical structure on NF-kappaB inhibitory activity.

PMID- 16570921
TI  - Novel, achiral 1,3,4-benzotriazepine analogues of 1,4-benzodiazepine-based CCK(2)
      antagonists that display high selectivity over CCK(1) receptors.
AB  - A series of 1,3,4-benzotriazepine-based CCK(2) antagonists have been devised by
      consideration of the structural features that govern CCK receptor affinity and
      the receptor subtype selectivity of 1,4-benzodiazepine-based CCK(2) antagonists.
      In contrast to the latter compounds, these novel 1,3,4-benzotriazepines are
      achiral, yet they display similar affinity for CCK(2) receptors to the earlier
      molecules and are highly selective over CCK(1) receptors.

PMID- 16570922
TI  - A hybrid mixture discriminant analysis-random forest computational model for the
      prediction of volume of distribution of drugs in human.
AB  - A computational approach is described that can predict the VD(ss) of new
      compounds in humans, with an accuracy of within 2-fold of the actual value. A
      dataset of VD values for 384 drugs in humans was used to train a hybrid mixture
      discriminant analysis-random forest (MDA-RF) model using 31 computed descriptors.
      Descriptors included terms describing lipophilicity, ionization, molecular
      volume, and various molecular fragments. For a test set of 23 proprietary
      compounds not used in model construction, the geometric mean fold-error (GMFE)
      was 1.78-fold (+/-11.4%). The model was also tested using a leave-class out
      approach wherein subsets of drugs based on therapeutic class were removed from
      the training set of 384, the model was recast, and the VD(ss) values for each of
      the subsets were predicted. GMFE values ranged from 1.46 to 2.94-fold, depending
      on the subset. Finally, for an additional set of 74 compounds, VD(ss) predictions
      made using the computational model were compared to predictions made using
      previously described methods dependent on animal pharmacokinetic data.
      Computational VD(ss) predictions were, on average, 2.13-fold different from the
      VD(ss) predictions from animal data. The computational model described can
      predict human VD(ss) with an accuracy comparable to predictions requiring
      substantially greater effort and can be applied in place of animal
      experimentation.

PMID- 16570924
TI  - Water-soluble bis(imidazolylporphyrin) self-assemblies with large two-photon
      absorption cross sections as potential agents for photodynamic therapy.
AB  - Two water-soluble porphyrin self-assemblies consisting of bisacetylene- and
      monoacetylene-linked conjugated bis(imidazolylporphyrin) have been synthesized.
      Two-photon absorption (2PA) cross section values in water were determined as 7500
      GM for bisacetylene- and 7900 GM for monoacetylene-linked bisporphyrin by
      femtosecond open-aperture Z-scan measurement. These values were almost the same
      as those for the similar structure reported previously in CHCl(3). Therefore, the
      structure is suggested to be similar in CHCl(3) and aqueous solutions. Both
      compounds were found to efficiently generate singlet oxygen upon one-photon
      irradiation in a manner similar to protoporphyrin, as demonstrated by the time
      resolved luminescence measurement at the characteristic band of 1270 nm.
      Photocytotoxicities for HeLa cancer cells were examined and found to be as high
      as those of hematoporphyrin, demonstrating that these newly prepared compounds
      are potential candidates as 2PA-photodynamic therapy agents.

PMID- 16570925
TI  - Determination and mapping of activity-specific descriptor value ranges for the
      identification of active compounds.
AB  - MAD (Mapping to Activity class-specific Descriptor value ranges) is a novel
      molecular similarity method that relies on the identification of activity
      specific descriptors. Applying a categorical descriptor scoring function, value
      ranges of molecular descriptors in screening databases are compared with those in
      classes of active compounds and descriptors displaying significant deviations are
      selected. In order to identify new actives, database molecules are mapped to
      class-specific value ranges and ranked using a similarity function. As a mapping
      algorithm, MAD is distinct from many other molecular similarity and virtual
      screening methods. In systematic virtual screening trials, for small selection
      sets of only 30 database compounds, average hit and recovery rates over six
      activity classes ranged from about 10% to 25% and about 25% to 75%, respectively.
      Moreover, when mining a database of bioactive molecules many similar compounds
      were selected (with hit rates between about 15% and 79%). Our findings suggest
      that it is possible to generate compound class-directed descriptor reference
      spaces for molecular similarity analysis.

PMID- 16570923
TI  - Design, synthesis, and evaluation of near infrared fluorescent multimeric RGD
      peptides for targeting tumors.
AB  - Molecular interactions between RGD peptides and integrins are known to mediate
      many biological and pathological processes. This has led to an increased interest
      in the development of RGD compounds with high affinity and improved selectivity
      for integrin receptors. In this study, we synthesized and evaluated a series of
      multimeric RGD compounds constructed on a dicarboxylic acid-containing near
      infrared (NIR) fluorescent dye (cypate) for tumor targeting. An array of NIR
      fluorescent RGD compounds was prepared efficiently, including one RGD monomer
      (cypate-(RGD)(2)-NH(2)), two RGD dimers (cypate-(RGD)(2)-NH(2) and cypate-(RGD
      NH(2))(2)), one trimer (cypate-(RGD)(3)-NH(2)), two tetramers (cypate-(RGD)(4)
      NH(2) and cypate-[(RGD)(2)-NH(2)](2)), one hexamer (cypate-[(RGD)(3)-NH(2)](2)),
      and one octamer (cypate-[(RGD)(4)-NH(2)](2)). The binding affinity of the
      multimeric RGD compounds for alpha(v)beta(3) integrin receptor (ABIR) showed a
      remarkable increase relative to the monomer cypate-RGD-NH(2). Generally, the
      divalent linear arrays of the multimeric RGD units bound the ABIR with slightly
      higher affinity than their monovalent analogues. These results suggest that the
      receptor binding affinity was not only dependent on the number of RGD moieties
      but also on the spatial alignments of the pendant peptides. Internalization of
      the compounds by ABIR-positive tumor cells (A549) was monitored by NIR
      fluorescence microscopy. The data showed that endocytosis of the octameric RGD
      derivative was significantly higher by comparison to other compounds in this
      study. In vivo noninvasive optical imaging and biodistribution data showed that
      the compounds were retained in A549 tumor tissue. These results clearly
      demonstrated that an array of simple RGD tripeptides on a NIR fluorescent dye
      core can be recognized by ABIR. Optimization of the spatial alignment of the RGD
      moieties through careful molecular design and library construction could induce
      multivalent ligand-receptor interactions useful for in vivo tumor imaging and
      tumor-targeted therapy.

PMID- 16570926
TI  - Discovery of orally efficacious melanin-concentrating hormone receptor-1
      antagonists as antiobesity agents. Synthesis, SAR, and biological evaluation of
      bicyclo[3.1.0]hexyl ureas.
AB  - Melanin-concentrating hormone (MCH) is a cyclic, nonadecapeptide expressed in the
      CNS of all vertebrates that regulates feeding behavior and energy homeostasis via
      interaction with the central melanocortin system. Regulation of this interaction
      results in modulation of food intake and body weight gain, demonstrating
      significant therapeutic potential for the treatment of obesity. The MCH-1
      receptor (MCH-R1) has been identified as a key target in MCH regulation, as small
      molecule antagonists of MCH-R1 have demonstrated activity in vivo. Herein, we
      document our research in a bicyclo[3.1.0]hexyl urea series with particular
      emphasis on structure-activity relationships and optimization of receptor
      occupancy, measured both in vitro and via an ex vivo binding assay following an
      oral dosing regimen. Several compounds have been tested in vivo and exhibit oral
      efficacy in relevant acute rodent feeding models. In particular, 24u has proven
      efficacious in chronic rodent models of obesity, showing a statistically
      significant reduction in food intake and body weight over a 28 day study.

PMID- 16570927
TI  - 1,4-Benzodiazepines as inhibitors of respiratory syncytial virus.
AB  - Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower
      respiratory tract infections worldwide and is increasingly being recognized as a
      serious threat to patient groups with poorly functioning immune systems. Our
      approach to finding a novel inhibitor of this virus was to screen a 20 000-member
      diverse library in a whole cell XTT assay. Parallel assays were carried out in
      the absence of virus in order to quantify any associated cell toxicity. This
      identified 100 compounds with IC(50)'s less than 50 muM. A-33903 (18), a 1,4
      benzodiazepine analogue, was chosen as the starting point for lead optimization.
      This molecule was moderately active and demonstrated good pharmacokinetic
      properties. The most potent compounds identified from this work were A-58568
      (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic
      substitution enhanced potency, and A-58175 (42), where the amide linker was
      modified.

PMID- 16570928
TI  - Development of the first potential covalent inhibitors of anandamide cellular
      uptake.
AB  - On the basis of the chemical structures of two previously developed metabolically
      stable and relatively potent inhibitors of anandamide uptake, OMDM-1,2, two
      series of potential covalent inhibitors of anandamide cellular reuptake, which
      might be used for the molecular characterization of the protein(s) involved in
      the membrane transport of endocannabinoids, have been designed and synthesized.
      Most of the compounds inhibited uptake to a varied extent and in a generally
      enantio-sensitive manner when co-incubated with [(14)C]anandamide, but only three
      of them, the photoactivatable 1a (OMDM-37), 1b (OMDM-39), and 8(Lo395), also
      produced a significant inhibition of uptake following the preincubation only of
      the cells, and this effect was significantly enhanced following UV exposure only
      in the case of 8. None of the new compounds inhibited [(14)C]anandamide
      hydrolysis with IC(50) < 50 microM, except for 1b.

PMID- 16570929
TI  - Oxyhomologues of anandamide and related endolipids: chemoselective synthesis and
      biological activity.
AB  - The three amide oxyhomologues of the endolipids N-arachidonoylethanolamine
      (anandamide, AEA, 1a), N-oleoylethanolamine (OEA, 2a), and N
      palmitoylethanolamine (PEA, 3a) have been prepared in a chemoselective way,
      capitalizing on the easy availability of O-[2
      (triisopropylsilyoxy)ethyl]hydroxylamine (6) and the surprising complementary
      selectivity observed in the acylation of N-[2-(tert
      butyldiphenylsilyloxy)ethyl]hydroxylamine (7) with the PPAA and the DCC/HOBT
      protocols. Reversal of the cannabinoid CB(1)/CB(2) receptor affinity ratio was
      observed for the first time in a derivative of anandamide (the O-alkyl-N-acyl
      hydroxylamine 1b), while the other oxyhomologues (1c and 1d) showed only marginal
      cannabimimetic activity. Compounds with unsaturated acyl chains generally
      retained vanilloid activity and showed an increased stability toward FAAH
      compared to their corresponding ethanolamides. Taken together, these observation
      show that oxyhomologation has a pronounced effect on both the pharmacodynamic and
      the pharmacokinetic properties of endogenous ethanolamides, suggesting a general
      relevance of this maneuver for the modification of amide pharmacophores.

PMID- 16570930
TI  - Screening for cardiovascular safety: a structure-activity approach for guiding
      lead selection of melanin concentrating hormone receptor 1 antagonists.
AB  - An inactin-anesthetized rat cardiovascular (CV) assay was employed in a screening
      mode to triage multiple classes of melanin-concentrating hormone receptor 1
      (MCHr1) antagonists. Lead identification was based on a compound profile
      producing high drug concentration in both plasma (>40 microM) and brain (>20
      microg/g) with <15% change in cardiovascular endpoints. As a result of these
      stringent requirements, lead optimization activities on multiple classes of MCHr1
      antagonists were terminated. After providing evidence that the cardiovascular
      liabilities were not a function of MCHr1 antagonism, continued screening
      identified the chromone-substituted aminopiperidine amides as a class of MCHr1
      antagonists that demonstrated a safe cardiovascular profile at high drug
      concentrations in both plasma and brain. The high incidence of adverse
      cardiovascular effects associated with an array of MCHr1 antagonists of
      significant chemical diversity, combined with the stringent safety requirements
      for antiobesity drugs, highlight the importance of incorporating cardiovascular
      safety assessment early in the lead selection process.

PMID- 16570931
TI  - Similarity based virtual screening: a tool for targeted library design.
AB  - High throughput screening drug discovery utilizes large and expensive compound
      libraries. As an alternative, a smaller targeted library can be constructed with
      the aid of the 3D structure of the target molecule. We used the X-ray crystal
      structure of a protein homologous to the selected target in creation of a small
      focused library and evaluated inhibition potential of this library against
      Chlamydia pneumoniae, a common pathogen recently linked to atherosclerosis and
      risk of myocardial infarction.

PMID- 16570932
TI  - Benzoylphenylurea sulfur analogues with potent antitumor activity.
AB  - A novel series of BPU analogues were synthesized and evaluated for antitumor
      activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up
      to 10-fold increased potency, when compared to 1 (NSC-639829), against cancer
      cell lines. 6n was more effective than 1 in causing apoptosis of MCF-7 cells.
      When compared to other drugs with a similar mechanism of action, 6n retained
      significant ability to inhibit tubulin assembly, with an IC(50) of 2.1 microM.

PMID- 16570933
TI  - Laser-induced potential jump at the electrochemical interface probed by
      picosecond time-resolved surface-enhanced infrared absorption spectroscopy.
AB  - Picosecond time-resolved surface-enhanced infrared absorption spectroscopy
      (SEIRAS) has been used for the first time to examine the potential jump at the
      electrochemical interface induced by a visible pulse irradiation. The potential
      dependent shift of the C-O stretching vibration of CO adsorbed on a Pt electrode
      was utilized to monitor the potential jump. A 6-cm(-1) red-shift was observed
      with a time delay of approximately 200 ps with respect to a visible pump-pulse
      irradiation (532 nm, 35 ps duration, 3 mJ cm(-2)). The observed red-shift is
      ascribed to the heating of the in-plane frustrated translational mode of CO and
      the negative shift of potential. These two contributions can be separated with
      the aid of the transient of the background reflectivity of the electrode surface.
      The heating of water layers near the surface is mainly responsible for the
      potential jump through the orientation change of water molecules. This method is
      promising as a tool to examine ultrafast electrode dynamics.

PMID- 16570934
TI  - Vibrational spectra of methane clathrate hydrates from molecular dynamics
      simulation.
AB  - Molecular dynamics simulations were performed on methane clathrate hydrates at
      ambient conditions. Thermal expansion results over the temperature range 60-300 K
      show that the unit cell volume increases with temperature in agreement with
      experiment. Power spectra were obtained at 273 K from velocity autocorrelation
      functions for selected atoms, and normal modes were assigned. The spectra were
      further classified according to individual atom types, allowing the assignment of
      contributions from methane molecules located in small and large cages within the
      structure I unit cell. The symmetric C-H stretch of methane in the small cages
      occurs at a higher frequency than for methane located in the large cages, with a
      peak separation of 14 cm(-1). Additionally, we determined that the symmetric C-H
      stretch in methane gas occurs at the same frequency as methane in the large
      cages. Results of molecular dynamics simulations indicate the use of power
      spectra obtained from the velocity autocorrelation function is a reliable method
      to investigate the vibrational behavior of guest molecules in clathrate hydrates.

PMID- 16570935
TI  - Block-copolymer-controlled growth of CaCO3 microrings.
AB  - A novel way for directed solution growth of hollow superstructures of CaCO3 has
      been successfully developed on the basis of controlled self-assembly and polymer
      concentration gradients using a double-hydrophilic block copolymer with a
      hydrophobic modification as a directing agent. A formation mechanism of such
      rings is proposed on the basis of the formation of CaCO3 nanoparticles in
      unstructured block copolymer assemblies with subsequent aggregation of these
      primary nanoparticles. This leads to the formation of a polymer concentration
      gradient from the inside to the outside of the particle. As the polymer contains
      multiple chelating units, this leads to a selective dissolution of the center of
      the particle.

PMID- 16570936
TI  - A new strategy for ratiometric fluorescence detection of transition metal ions.
AB  - A novel design strategy for ratiometric fluorescence signaling of transition
      metal ions, involving both photoinduced electron transfer and resonance energy
      transfer mechanisms, has been tested on a model system comprising dual
      fluorophores.

PMID- 16570937
TI  - Generation of detectable singlet aryl cations by photodehalogenation of
      fluoroquinolones.
AB  - Nanosecond laser flash photolysis (lambdaexc = 355 nm) of neutral aqueous
      solutions of lomefloxacin (LFX, a 8-fluorinated 7-amino-4-quinolone-3-carboxylic
      acid derivative) produces a detectable transient species, which shows an
      absorption maximum at 490 nm and can be assigned to an aryl cation. This
      intermediate has a lifetime of ca. 200 ns in net water, reacts with Br- and Cl-
      with rate constants of 3.6 x 10(9) M(-1) s(-1) and 4.1 x 10(8) M(-1) s(-1),
      respectively, and shows a lack of reactivity toward molecular oxygen. From the
      photolysis of BAY y3118 (BAY, a 8-chlorinated analogue), an aryl cation is also
      generated, showing absorption maximum at 480 nm (lifetime of ca. 1 micros in net
      water) and a reaction rate constant of 9 x 10(9) M(-1) s(-1) with Br(-). The
      existence of these highly reactive species arising from direct photolysis of LFX
      and BAY can justify the photogenotoxic properties associated with these
      antibacterial drugs likely due to direct reaction of their cations with DNA.

PMID- 16570938
TI  - Quantitative classification of covalent and noncovalent H-bonds.
AB  - The covalent nature of interactions within various hydrogen bonded molecular
      aggregates has been characterized by the two entirely different computational
      methods: Bader analysis of the electron density and variation-perturbation
      partitioning of the intermolecular interaction energy. Analysis of 34 complexes
      representing different types of hydrogen bonds indicates that the proton-acceptor
      distance approximately 1.8 A and the ratio of delocalization and electrostatic
      terms approximately 0.45 constitutes approximately a borderline between covalent
      and noncovalent hydrogen bonds. The latter ratio could be used to characterize
      quantitatively the degree of the covalent nature of transition state interactions
      with active site residues, a quantity essential for an enzyme catalytic activity.

PMID- 16570939
TI  - Templated carbon nanofiber with mesoporosity and semiconductivity.
AB  - We have newly fabricated a long one-dimensional (1D) mesoporous carbon nanofiber
      by using a mesoporous silica nanofiber template. The resulting mesoporous carbon
      nanofiber shows the unique mesoporous structure of circularly wound nanochannel
      alignment perpendicular to the long fiber axis and the high gas sorption
      property, which interestingly presents the p-type semiconducting behavior.

PMID- 16570940
TI  - NC-AFM observation of atomic scale structure of rutile-type TiO2(110) surface
      prepared by wet chemical process.
AB  - We succeeded in observing the atomic scale structure of a rutile-type TiO2(110)
      single-crystal surface prepared by the wet chemical method of chemical etching in
      an acid solution and surface annealing in air. Ultrahigh vacuum noncontact atomic
      force microscopy (UHV-NC-AFM) was used for observing the atomic scale structures
      of the surface. The UHV-NC-AFM measurements at 450 K, which is above a desorption
      temperature of molecularly adsorbed water on the TiO2(110) surface, enabled us to
      observe the atomic scale structure of the TiO2(110) surface prepared by the wet
      chemical method. In the UHV-NC-AFM measurements at room temperature (RT),
      however, the atomic scale structure of the TiO2(110) surface was not observed.
      The TiO2(110) surface may be covered with molecularly adsorbed water after the
      surface was prepared by the wet chemical method. The structure of the TiO2(110)
      surface that was prepared by the wet chemical method was consistent with the (1 x
      1) bulk-terminated model of the TiO2(110) surface.

PMID- 16570941
TI  - Lithium exchange processes in the conduction network of the Nasicon LiTi2
      xZrx(PO4)3 Series (0 < or = x < or = 2).
AB  - Structural sites occupied by lithium in the rhombohedral LiTi2-xZrx(PO4)3 series
      (0 < or = x < or = 2) have been investigated by 7Li NMR spectroscopy. At room
      temperature, the XRD patterns of the end-members of the series display
      rhombohedral R3c symmetry in LiTi2(PO4)3 and triclinic C in LiZr2(PO4)3. In the
      first compound, Li ions occupy M1 sites; however, in the second one Li occupy
      intermediate M1/2 sites. As the temperature increases, a first-order displacive
      transformation is detected in the triclinic phase, but a second-order/disorder
      transition is detected in the rhombohedral phase. From the temperature dependence
      of the 7Li NMR quadrupole constant (CQ) of the two compounds, the evolution of M1
      and M1/2 sites occupancy in the Nasicon conduction network has been deduced. At
      high temperatures, analyzed phases tend toward a disordered rhombohedral phase,
      in which both M1 and M1/2 sites are equally populated and in which lithium
      mobility is favored by the existence of vacant M1 sites. According to this study,
      this phase can also be obtained by substituting Ti by Zr in the LiTi2-xZrx(PO4)3
      series.

PMID- 16570943
TI  - Carbon nanotube bundles as molecular assemblies for the detection of polycyclic
      aromatic hydrocarbons: surface-enhanced resonance Raman spectroscopy and
      theoretical studies.
AB  - In this work surface-enhanced resonance Raman spectroscopic experiments have
      demonstrated that metallic single-walled carbon nanotubes can be used as chemical
      assemblies between the pyrene analyte and the silver colloidal surface. Pyrene
      has been detected at concentrations lower than 10(-9) M by use of the 514.5 nm
      excitation laser line. A charge transfer from the surface to the nanotube
      characterizes the nanotube-silver surface interaction. The pyrene-nanotube
      interaction occurs through a pi-pi electronic stacking. Extended Huckel
      calculations based on a simplified molecular model for the
      analyte/nanotube/surface system support the experimental conclusions. The
      nanotube-pyrene distance is 3.4 A, and the most probable orientation for pyrene
      is confirmed to be plane parallel to the nanotube surface. An energy transfer
      from the silver surface to the nanotube/analyte system is verified.

PMID- 16570942
TI  - Development of effective quantum mechanical/molecular mechanical (QM/MM) methods
      for complex biological processes.
AB  - Motivated by the long-term goal of understanding vectorial biological processes
      such as proton transport (PT) in biomolecular ion pumps, a number of developments
      were made to establish combined quantum mechanical/molecular mechanical (QM/MM)
      methods suitable for studying chemical reactions involving significant charge
      separation in the condensed phase. These developments were summarized and
      discussed with representative problems. Specifically, free energy perturbation
      and boundary potential methods for treating long-range electrostatics were
      implemented to test the robustness of QM/MM results for protein systems. It was
      shown that consistent models with sufficient sampling were able to produce
      quantitatively satisfactory results, such as pKa for titritable groups in the
      interior of T4-lysozyme, while an inconsistent treatment of electrostatics or
      lack of sufficient sampling may produce incorrect results. Modifications were
      made to an approximate density functional theory (SCC-DFTB) to improve the
      description of proton affinity and hydrogen-bonding, which are crucial for the
      treatment of PT in polar systems. Test calculations on water autoionization
      showed clearly that both improvements are necessary for quantitatively reliable
      results. Finally, the newly established SCC-DFTB/MM-GSBP protocol was used to
      explore mechanistic issues in carbonic anhydrase (CA). Preliminary results
      suggest that PT in CA occurs mainly through short water wires containing two
      water molecules in a thermally activated fashion. Although longer water wires
      occur with similar frequencies, PT along those pathways, on average, has
      substantially higher barriers, a result not expected based on previous studies.
      The fluctuations of water molecules peripheral to the water wire were found to
      make a larger impact on the PT energetics compared to polar protein residues in
      the active site, which are largely pre-organized and therefore have less tendency
      to reorganize during the reaction.

PMID- 16570944
TI  - Probing the formation mechanism and chemical states of carbon-supported Pt-Ru
      nanoparticles by in situ X-ray absorption spectroscopy.
AB  - The understanding of the formation mechanism of nanoparticles is essential for
      the successful particle design and scaling-up process. This paper reports
      findings of an X-ray absorption spectroscopy (XAS) investigation, comprised of X
      ray absorption near-edge structure (XANES) and extended X-ray absorption fine
      structure (EXAFS) regions, to understand the mechanism of the carbon-supported Pt
      Ru nanoparticles (NPs) formation process. We have utilized Watanabe's colloidal
      reduction method to synthesize Pt-Ru/C NPs. We slightly modified the Watanabe
      method by introducing a mixing and heat treatment step of Pt and Ru oxidic
      species at 100 degrees C for 8 h with a view to enhance the mixing efficiency of
      the precursor species, thereby one can achieve improved homogeneity and atomic
      distribution in the resultant Pt-Ru/C NPs. During the reduction process, in situ
      XAS measurements allowed us to follow the evolution of Pt and Ru environments and
      their chemical states. The Pt LIII-edge XAS indicates that when H2PtCl6 is
      treated with NaHSO3, the platinum compound is found to be reduced to a Pt(II)
      form corresponding to the anionic complex [Pt(SO3)4]6-. Further oxidation of this
      anionic complex with hydrogen peroxide forms dispersed [Pt(OH)6]2- species.
      Analysis of Ru K-edge XAS results confirms the reduction of RuIIICl3 to
      [RuII(OH)4]2- species upon addition of NaHSO3. Addition of hydrogen peroxide to
      [RuII(OH)4]2- causes dehydrogenation and forms RuOx species. Mixing of [Pt(OH)6]2
      and RuOx species and heat treatment at 100 degrees C for 8 h produced a
      colloidal sol containing both Pt and Ru metallic as well as ionic contributions.
      The reduction of this colloidal mixture at 300 degrees C in hydrogen atmosphere
      for 2 h forms Pt-Ru nanoparticles as indicated by the presence of Pt and Ru atoms
      in the first coordination shell. Determination of the alloying extent or atomic
      distribution of Pt and Ru atoms in the resulting Pt-Ru/C NPs reveals that the
      alloying extent of Ru (JRu) is greater than that of the alloying extent of Pt
      (JPt). The XAS results support the Pt-rich core and Ru-rich shell structure with
      a considerable amount of segregation in the Pt region and with less segregation
      in the Ru region for the obtained Pt-Ru/C NPs.

PMID- 16570945
TI  - Triplet excitation energy transfer in porphyrin-based donor--bridge--acceptor
      systems with conjugated bridges of varying length: an experimental and DFT study.
AB  - A series of donor--bridge--acceptor (D--B--A) systems with varying donor-acceptor
      distances have been studied with respect to their triplet energy transfer
      properties. The donor and acceptor moieties, zinc(II), and free-base porphyrin,
      respectively, were separated by 2-5 oligo-p-phenyleneethynylene units (OPE)
      giving rise to edge-to-edge separations ranging between 12.7 and 33.4 A. The
      study was performed in 2-MTHF at 150 K and it was established that triplet
      excitation energy transfer occurs with high efficiency in all of the studied D--B
      -A systems. The distance dependence was exponential with an attenuation factor,
      beta, equal to 0.45 +/- 0.015 A(-1). The experimental study was also supported by
      quantum mechanical DFT and TD-DFT calculations on a series of closely related
      model systems. A thorough analysis of the OPE-bridge conformational dynamics led
      to an equation that quantitatively models the distance dependence of the
      electronic coupling found in the experimental study.

PMID- 16570946
TI  - Origin of the photoinduced optical second harmonic generation arising in N-phenyl
      microcrystalline films.
AB  - Photoinduced second-order nonlinear optical effects, particularly optical second
      harmonic generation (SHG) of N-phenyls with different numbers of aromatic rings
      deposited on glass substrates were studied. As a fundamental beam, a 5-ps pulsed
      Nd:YAG laser was used. Quantum chemical time-dependent density functional theory
      (TDDFT) simulations of the nonlinear optical properties were performed. The first
      order hyperpolarizabilities of isolated molecules were calculated, under the
      influence of a polarized pumping beam, to evaluate the role played by the
      nanointerfaces separating the microcrystallites and the amorphous environment.
      Consideration was performed within a framework of steady-state Langevin order
      parameters for amorphous-like films. A strong dependence of the photoinduced SHG
      versus the number of aromatic rings determining the degree of film crystallinity
      was shown. A comparison of experimental data and theoretically evaluated results
      shows that for the photoinduced first-order nonlinear optical effect the dominant
      contribution is an amorphous-like structural component, unlike the transport
      properties, where the crucial role is played by the nanointerface region. This
      may reflect a specific feature of the multiphoton processes in such types of
      nanointerfaces because of nanoconfined effects.

PMID- 16570947
TI  - Photophysical studies of alpha,omega-dicyano-oligothiophenes NC(C4H2S)nCN (n = 1
      6).
AB  - The photophysics of six oligothiophenes end-capped with cyano groups (CNalphan)
      was investigated in solution at room and low temperature. The study comprises
      singlet-singlet and triplet-triplet absorption and emission spectra together with
      lifetimes and quantum yields for all the radiative and nonradiative processes.
      From the lifetimes and quantum yields, it was possible to extract the rate
      constants for all the processes. Singlet oxygen yields were also determined,
      revealing an efficient sensitization (SDelta approximately 1) of its formation by
      the triplet state of the CNalphan. The introduction of the cyano groups is found
      to decrease the energetic separation between the highest occupied molecular
      orbital and the lowest unoccupied molecular orbital, leading to a red shift of
      the absorption and the emission when compared with the unsubstituted
      counterparts, the alpha-oligothiophenes. Phosphorescence is only observed for the
      first member of the series, CNalpha1.

PMID- 16570948
TI  - Binding studies of molecular linkers to ZnO and MgZnO nanotip films.
AB  - Two bifunctional linkers, a rigid-rod p-ethynyl-isophthalic acid capped with a
      Ru(II)-polypyridyl complex and 3-mercaptopropionic acid, were covalently bound to
      ZnO nanotip films grown by metal-organic chemical vapor deposition (MOCVD)
      technology. This highly vertically aligned, crystalline form of ZnO had not been
      functionalized before. The binding was studied by Fourier transform (FT) IR and
      UV spectroscopies and probed, in the case of the Ru complex, by static and
      dynamic fluorescence quenching. The molecules did bind through the carboxylic
      acid groups, and the FT-IR attenuated total reflectance spectra are indicative of
      a bidentate carboxylate binding mode. Other molecules (heptanoic acid,
      isophthalic acid, and trimethoxy(2-phenylethyl)silane) were also bound to the ZnO
      nanotips. A comparison was made with epitaxial ZnO films grown by MOCVD and ZnO
      mesoporous films prepared from colloidal solutions to investigate the effect of
      the ZnO morphology. The ZnO nanotips were excellent binding substrates,
      particularly for the rigid-rod linker. Since ZnO films are etched at low pH (<
      4), novel nanotip films made of ternary MgxZn1-xO, which is formed by alloying
      ZnO with MgO and is more resistant to acids, were developed. The MgxZn1-xO
      nanotip films were employed to use linkers with acidic groups and to study the
      effect of pH pretreatment of the surface on the binding.

PMID- 16570949
TI  - Prolongation of the lifetime of the charge-separated state at low temperatures in
      a photoinduced electron-transfer system of [60]fullerene and ferrocene moieties
      tethered by rotaxane structures.
AB  - A rotaxane tethering both fullerene (C60) and ferrocene (Fc) moieties
      (abbreviated as (C60;Fc)rotax+) was synthesized in a good yield by the urethane
      end-capping of pseudorotaxane based on the crown ether-secondary amine motif. In
      (C60;Fc)rotax+, the C60 group serving as an electron acceptor is attached to the
      crown ether wheel, through which the axle with a Fc group acting as an electron
      donor on its end penetrates. The intrarotaxane photoinduced energy-transfer and
      electron-transfer processes between C60 and Fc in (C60;Fc)rotax+ have been
      investigated by time-resolved transient absorption and fluorescence measurements
      with changing solvent polarity. Nanosecond transient absorption measurements of
      the rotaxane demonstrated that the charge-separated state (C60*-;Fc*+)rotax+ is
      formed mainly via the excited triplet state of C60 in polar solvents. The
      lifetime of (C60*-;Fc*+)rotax+ was evaluated to be 20 ns in dimethylformamide
      (DMF) at room temperature. With lowing temperature, the lifetime of (C60*
      ;Fc*+)rotax+ extends to 270 ns in DMF at -65 degrees C, due to the structural
      changes leaving C60*- and Fc*+ at a relatively long distance in the low
      temperature region.

PMID- 16570951
TI  - Spectroscopy of auramine fluorescent probes free and bound to poly(methacrylic
      acid).
AB  - Auramines containing a vinyl group with strong electron-withdrawing substituent
      exhibit a pi-conjugated extended effect that gives a red shift in their
      absorption and emission bands. The new fluorochromic dyes were bound to
      poly(methacrylic acid) (PMA), and their photophysical dynamics in methanol and in
      aqueous solution were studied. These derivatives were also used as optical probes
      for copolymerization process. The process was monitored by the changes in
      electronic absorption with a concomitant fading of the free vinyl auramine
      absorption band in the red and an appearance of a UV band ascribed to dye bound
      to the polymer chain. The conformational transition of PMA with solvent and pH
      was clearly observed by the drastic changes in the photophysical properties of
      these auramine derivatives attached to the polymer chain. Time-resolved
      experiments revealed an unusual long-lived decay component of about 2.2-2.6 ns in
      aqueous solution at low pH together with two picosecond components (50 and 570
      ps). Such long decay was only reported in the literature for auramine adsorbed in
      solid matrices. It was ascribed to the fraction of bound auramine in a region of
      compact coil of PMA.

PMID- 16570950
TI  - Molecular structure and bonding of copper cluster monocarbonyls CunCO (n = 1-9).
AB  - In this work we analyze CO binding on small neutral copper clusters, Cun (n = 1
      9). Molecular structures and reactivity descriptors of copper clusters are
      computed and discussed. The results show that the condensed Fukui functions and
      the frontier molecular orbital theory are useful tools to predict the selectivity
      of CO adsorption on these small clusters. To get further insight into the CO
      binding to copper clusters, an energy decomposition analysis of the CO binding
      energy is performed. The Cs symmetry of the formed CunCO clusters (n = 1-8)
      allows the separation between the orbital interaction terms corresponding to
      donation and back-donation. It is found that, energetically, the donation is
      twice as important as back-donation.

PMID- 16570952
TI  - Controlled synthesis of high-quality PbS star-shaped dendrites, multipods,
      truncated nanocubes, and nanocubes and their shape evolution process.
AB  - Well-defined single-crystalline PbS nano- and microstructures including
      dendrites, multipods, truncated nanocubes, and nanocubes were synthesized in high
      yield by a simple solution route. Novel star-shaped PbS dendrites with six
      symmetric arms along the 100 direction, each of which shows one trunk (long axis)
      and four branches (short axes), have been achieved using Pb(AC)2 and
      thioacetamide (TAA) as precursors, under the molar ratio Pb(AC)2/TAA = 2/1, at
      initial reaction temperature 80 degrees C, refluxing for 30 min at 100 degrees C,
      in the presence of cetyltrimethylammonium bromine (CTAB). The "nanorods" in each
      branch are parallel to each other in the same plane and are perpendicular to the
      trunk. The truncated nanocubes mainly bounded by the {100} plane were prepared
      under a different Pb(AC)2/TAA molar ratio, at initial reaction temperature 40
      degrees C, refluxing for 12 h at 100 degrees C. Based on the systematic studies
      on their shape evolution, a possible growth mechanism of these PbS nano- and
      microstructures was proposed. The shapes of PbS nanocrystals with face-centered
      cubic (fcc) structure are mainly determined by the ratio (R) between the growth
      rates along the (100) and (111) directions. The Pb(AC)2/TAA molar ratio and the
      initial reaction temperature influence the growth ratio R in the formation of PbS
      nuclei at an early stage, which results in the final morphology of PbS
      nanocrystals. Under the current experimental conditions, we can control the PbS
      shape evolution by simply tuning the molar ratio, the initial reaction
      temperature, and the period of reaction. Based on the systematic studies on the
      shape evolution, this approach is expected to be employed for the control-shaped
      synthesis of other fcc structural semiconductor nanomaterials. The
      photoluminescence properties were investigated and the prepared nano- and
      microstructures displayed a very strong luminescence around 600-650 nm at room
      temperature.

PMID- 16570953
TI  - Detecting gas hydrate behavior in crude oil using NMR.
AB  - Because of the associated experimental difficulties, natural gas hydrate behavior
      in black oil is poorly understood despite its grave importance in deep-water flow
      assurance. Since the hydrate cannot be visually observed in black oil,
      traditional methods often rely on gas pressure changes to monitor hydrate
      formation and dissociation. Because gases have to diffuse through the liquid
      phase for hydrate behavior to create pressure responses, the complication of gas
      mass transfer is involved and hydrate behavior is only indirectly observed. This
      pressure monitoring technique encounters difficulties when the oil phase is too
      viscous, the amount of water is too small, or the gas phase is absent. In this
      work we employ proton nuclear magnetic resonance (NMR) spectroscopy to observe
      directly the liquid-to-solid conversion of the water component in black oil
      emulsions. The technique relies on two facts. The first, well-known, is that
      water becomes essentially invisible to liquid state NMR as it becomes immobile,
      as in hydrate or ice formation. The second, our recent finding, is that in high
      magnetic fields of sufficient homogeneity, it is possible to distinguish water
      from black oil spectrally by their chemical shifts. By following changes in the
      area of the water peak, the process of hydrate conversion can be measured, and,
      at lower temperatures, the formation of ice. Taking only seconds to accomplish,
      this measurement is nearly direct in contrast to conventional techniques that
      measure the pressure changes of the whole system and assume these changes
      represent formation or dissociation of hydrates - rather than simply changes in
      solubility. This new technique clearly can provide accurate hydrate thermodynamic
      data in black oils. Because the technique measures the total mobile water with
      rapidity, extensions should prove valuable in studying the dynamics of phase
      transitions in emulsions.

PMID- 16570954
TI  - Multinuclear solid-state high-resolution and 13C -{27Al} double-resonance magic
      angle spinning NMR studies on aluminum alkoxides.
AB  - A combination of 27Al magic-angle spinning (MAS)/multiple quantum (MQ)-MAS, 13C
      1H CPMAS, and 13C-{27Al} transfer of population in double-resonance (TRAPDOR)
      nuclear magnetic resonance (NMR) were used for the structural elucidation of the
      aluminum alkoxides aluminum ethoxide, aluminum isopropoxide, and aluminum
      tertiarybutoxide. Aluminum alkoxides exist as oligomers with aluminum in
      different coordinations. High-resolution 27Al MAS NMR experiments with high
      spinning speed distinguished the aluminum atoms in different environments. The
      27Al MAS NMR spectrum gave well-resolved powder patterns with different
      coordinations. Z-filter MQ-MAS was performed to obtain the number and types of
      aluminum environments in the oligomeric structure. 13C-1H CPMAS chemical shifts
      resolved the different carbon species (-CH3, =CH2, =CH-, and =C=) in the
      structures. 13C-{27Al} TRAPDOR experiments were employed to obtain relative Al-C
      dipolar interactions and to distinguish between terminal and bridging alkoxides
      in the crystallographic structures. The complete characterization of selected
      aluminum alkoxides using advanced NMR methods has evidenced the tetrameric
      structure for aluminum isopropoxide and the dimeric structure for aluminum
      tertiary-butoxide, as reported in the literature, and proposed a polymeric
      structure for aluminum ethoxide.

PMID- 16570955
TI  - Incorporation of trivalent cations in synthetic garnets A3B5O12 (A = Y, Lu-La, B
      = Al, Fe, Ga).
AB  - Static-lattice atomistic calculations have been used to study the solution energy
      for the incorporation of 13 foreign cations at 3 different lattice positions of
      12 synthetic garnets. Trends have been obtained as a function of the ionic radius
      of the dopant cation, and the predictions about site preference have been
      compared with both literature and experimental data. The preferred substitution
      site is mainly determined by the ionic size and has been correctly predicted in
      all cases. Moreover, the energy difference between the preferred substitution
      site and the next favored site is relatively small in several cases, and hence
      the foreign ions can be inserted at two different positions by using the correct
      stoichiometry. A remarkably different behavior has been encountered for Al
      garnets, due to the smaller size of the unit cell. In particular, some cations,
      such as Fe3+ and Ga3+, can be inserted at the dodecahedral position usually
      occupied by the rare-earth ion. Despite the limitations of the static-lattice
      approach, the results of the present simulations help in the understanding of the
      defect chemistry of garnets, which is strongly responsible for the
      physicochemical properties (such as luminescence and ferrimagnetism) that make
      garnets interesting for technological applications. Such results lead to the
      possibility of tuning the optical and luminescence properties of garnets by the
      formation of different types of solid solutions.

PMID- 16570956
TI  - Thermal stability and reactivity of metal halide filled single-walled carbon
      nanotubes.
AB  - Thermal stability and reactivity to oxidation of several nanocomposite systems
      obtained by encapsulation of metal halides in single-walled carbon nanotubes are
      studied. Thermogravimetric analysis coupled with Raman spectroscopy allows
      insight into the various contributing factors, such as charge transfer, strain,
      and defect formation, and establishing a hierarchy of reactivity for the systems
      studied (AgX@SWCNTs, with X = Br, I; SWCNTs = arc discharge and HiPCO). The
      activation energy for oxidation decreases considerably after filling, indicating
      that filled nanotubes are more amenable to controlled modifications based on
      chemical reactivity than the originating empty nanotubes. The complete removal of
      the carbon shell at high temperatures does not preserve the nanowire morphology
      of the encapsulated halides; these are freed on surfaces in the form of
      nanoparticles arranged in 1D patterns. Metallic nanoparticles were obtained after
      hydrogen reduction of the halides, and growth of silicon nanowires in the
      footprint of the originating nanocomposites was demonstrated from such Co seeds.
      MX@SWCNTs (M = Ag, Co) can thus be used as environmentally stable nanoscale
      containers that allow the deliverance of catalytic nanoparticles in a
      prepatterned and aligned way.

PMID- 16570957
TI  - Detailed model of the aggregation event between two fractal clusters.
AB  - A model has been developed for describing the aggregation process of two fractal
      clusters under quiescent conditions. The model uses the approach originally
      proposed by Smoluchowski for the diffusion-limited aggregation of two spherical
      particles but accounts for the possibility of interpenetration between the
      fractal clusters. It is assumed that when a cluster diffuses toward a reference
      cluster their center-to-center distance can be smaller than the sum of their
      radii, and their aggregation process is modeled using a diffusion-reaction
      equation. The reactivity of the clusters is assumed to depend on the reactivity
      and number of their particles involved in the aggregation event. The model can be
      applied to evaluate the aggregation rate constant as a function of the prevailing
      operating conditions by simply changing the value of the particle stability
      ratio, without any a priori specification of a diffusion-limited cluster
      aggregation, reaction-limited cluster aggregation, or transition regime.
      Furthermore, the model allows one to estimate the structure properties of the
      formed cluster after the aggregation, based on the computed distance between the
      aggregating clusters in the final cluster.

PMID- 16570958
TI  - Vanadium-containing mesoporous silica of high photocatalytic activity and
      stability even in water.
AB  - Vanadium-containing mesoporous silica molecular sieve (V proportional HMS) with
      tetrahedrally coordinated V-oxide species (VVO4) has been prepared by a modified
      surfactant-templating method, consisting of an addition of surfactant to a
      mixture of water, alcohol, and Si and V precursors followed by calcination. The V
      proportional HMS demonstrates high photocatalytic activity even in the presence
      of water, while other V proportional HMS's prepared by conventional templating
      methods and V/HMS prepared by an impregnation method show almost no activity
      owing to hydrolysis of the VVO4 species. ESR and photoluminescence measurements
      reveal that the modified templating method creates VVO4 species confined within a
      silica layer, while other methods create VVO4 species exposed on silica surface.
      The former VVO4 species are highly stabilized by the confinement within the
      silica, thus suppressing the hydrolysis. Another notable property of the confined
      VVO4 species is the higher photocatalytic activity even without water, despite
      their confined structure. This is explained by higher electrophilicity and longer
      lifetime of the excited-state VVO4 species (VIVO4*) derived from their distorted
      structure. The obtained findings suggest potential use of the modified surfactant
      templating method for synthesis of stable and recyclable V-containing mesoporous
      silica with high photocatalytic activity.

PMID- 16570959
TI  - Gold nanostructures from cube-shaped crystalline intermediates.
AB  - Conventional bottom-up approaches for building nanostructures rely on the ability
      to synthesize nanoparticles of different shapes and sizes in a controlled manner
      that are then assembled to produce useful structures. Here, we present an
      alternate approach for producing nanostructures based on the formation of a
      crystalline intermediate in which the metal ion can be reduced in a controlled
      manner. Partial reduction of HAuCl4 by a long-chain amine results in the
      formation of a cube-shaped crystalline intermediate in which Au is present in a
      +1 oxidation state. By control of the nucleation of the metal in the
      intermediate, a variety of nanostructures can be synthesized. Here, we present
      results on the formation of superlattices, hollow cubes, nanotubes, and extended
      hollow structures starting from the intermediate. Direct evidence for the
      formation of metal within the intermediate by in situ electron-beam-induced
      reduction in the transmission electron microscope is presented.

PMID- 16570960
TI  - Characterization of interactions in aqueous solutions of hydroxyethylcellulose
      and its hydrophobically modified analogue in the presence of a cyclodextrin
      derivative.
AB  - The formation of associative networks in semidilute aqueous solutions of
      hydrophobically modified hydroxyethylcellulose (HM-HEC) is dependent on
      intermolecular hydrophobic interactions. Addition of hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) monomers to the system provides decoupling of these
      associations via inclusion complex formation with the polymer hydrophobic tails.
      Results from viscosity, polymer NMR self-diffusion, and dynamic light scattering
      (DLS) measurements show that the hydrophobic interactions in HM-HEC solutions are
      effectively suppressed when the level of HP-beta-CD addition increases. Small
      angle neutron scattering (SANS) results reveal that the large-scale association
      complexes in HM-HEC solutions are strongly diminished when the concentration of
      HP-beta-CD rises. The time correlation data obtained from the DLS experiments
      unveiled the existence of two relaxation modes: one single exponential at short
      times followed by a stretched exponential at longer times. The fast mode is
      always diffusive, whereas the slow mode exhibits progressively stronger
      wavevector dependence as the intensity of the hydrophobic interactions increases.
      This feature, as well as the accompanying drop of the stretched exponential beta
      as the HP-beta-CD concentration decreases, is attributed to enhanced hydrophobic
      interactions and can be well rationalized in the framework of the coupling model
      of Ngai.

PMID- 16570961
TI  - Synthesis and formation mechanism of nanoneedles and nanorods of manganese oxide
      octahedral molecular sieve using an ionic liquid.
AB  - Single-crystalline cryptomelane-type manganese oxide octahedral molecular sieve
      (OMS-2) nanoneedles and nanorods were prepared by a solution-phase approach in
      the presence of an ionic liquid 1-n-butyl-3-methylimidazolium tetrafluoroborate
      ([BMIM]BF4). [BMIM]BF4 can act as a cosolvent, structure-directing agent, and
      reducing reagent in the reaction system. Based on the redox reaction of MnCl2 and
      KMnO4 in the mixed solvents of water and [BMIM]BF4, the formation of OMS-2
      nanoneedles followed the rolling mechanism with lamellae as an intermediate.
      However, the direct reaction of KMnO4 with [BMIM]BF4 resulted in the formation of
      OMS-2 nanorods with diameters as small as 3-6 nm. The formation mechanism of OMS
      2 nanostructures was discussed.

PMID- 16570962
TI  - One-step synthesis of monodisperse silver nanoparticles beneath vitamin E
      Langmuir monolayers.
AB  - The monodisperse silver nanoparticles were synthesized by one-step reduction of
      silver ions in the alkaline subphase beneath vitamin E (VE) Langmuir monolayers.
      The monolayers and silver nanocomposite LB films were characterized by surface
      pressure-area (pi-A) isotherms, transmission electron microscopy (TEM),
      ultraviolet-visible spectroscopy (UV-vis), selected area electron diffraction
      (SAED), Fourier transform infrared transmission spectroscopy (FTIR), and X-ray
      photoelectron spectroscopy (XPS), respectively. The results showed that the
      limiting area/VE molecule on different subphases varied. The phenolic groups in
      the VE molecules were converted to a quinone structure, and the silver ions were
      mainly reduced to ellipsoidal and spherical nanoparticles. The arrangement of the
      nanoparticles changed from sparseness to compactness with reaction time. The
      electron diffraction pattern indicated that the silver nanoparticles were face
      centered cubic (fcc) polycrystalline. Silver nanocomposite LB films with
      excellent quality could be formed on different substrates, indicating that the
      transfer ratio of monolayer containing silver nanoparticles is close to unity.
      The dynamic process of reduction of silver ions by VE LB films was also studied
      through monitoring the conductivity of an Ag2SO4 alkaline solution.

PMID- 16570963
TI  - Growth of SnO nanobelts and dendrites by a self-catalytic VLS process.
AB  - This article reports on the growth of SnO nanobelts and dendrites by a
      carbothermal reduction process. The materials were synthesized in a sealed tube
      furnace at 1210 degrees C and at 1260 degrees C for 2 h, in a dynamic nitrogen
      atmosphere of 40 sccm. After synthesis, gray-black materials were collected
      downstream in the tube and the samples were characterized by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X
      ray spectroscopy (EDX). The results showed that the gray-black materials were
      composed of nanobelts, which grew in the [110] direction of the orthorhombic
      structure of SnO. Some of the belts also presented dendritic growth. The
      dendrites grew in the (110) planes of the SnO structure, and no defects were
      observed at the junction between the nanobelts and the dendrites. A self
      catalytic vapor-liquid-solid (VLS) process was proposed to explain the growth of
      the SnO nanobelts and dendrites.

PMID- 16570964
TI  - Synthesis and characterization of ultrahigh crystalline TiO2 nanotubes.
AB  - Ultrahigh crystalline TiO2 nanotubes were synthesized by hydrogen peroxide
      treatment of very low crystalline titania nanotubes (TiNT-as prepared), which
      were prepared with synthesized TiO2 nanoparticles by hydrothermal methods in an
      aqueous NaOH solution. Thus, prepared ultrahigh crystalline TiO2 nanotubes (TiNT
      H2O2) showed comparable crystallinity with high crystalline TiO2 nanoparticles.
      The details of nanotubular structures were elucidated by high resolution
      transmission electron microscopy (HR-TEM), field emission-scanning electron
      microscopy (FE-SEM), energy-dispersive X-ray analysis in transmission electron
      microscopy (TEM-EDX), X-ray diffraction (XRD), photoluminescence (PL), and BET
      surface area. TiNT-H2O2 was found to be a multiwalled anatase phase only with an
      average outer diameter of approximately 8 nm and an inner diameter of
      approximately 5 nm and grown along the [001] direction to 500-700 nm long with an
      interlayer fringe distance of ca. 0.78 nm. The photocatalytic activity of TiNT
      H2O2 was about 2-fold higher than those of TiNT-as prepared, synthesized TiO2
      nanoparticles, and TiO2-P25 (Degussa) in the photocatalytic oxidation of
      trimethylamine gas under UV irradiation.

PMID- 16570965
TI  - Noncovalent functionalization of multiwalled carbon nanotubes: application in
      hybrid nanostructures.
AB  - We developed a reproducible, noncovalent strategy to functionalize multiwalled
      carbon nanotubes (MWNTs) via embedding nanotubes in polysiloxane shells. (3
      Aminopropyl)triethoxysilane molecules adsorbed to the nanotube surfaces via
      hydrophobic interactions are polymerized simply by acid catalysis and form a thin
      polysiloxane layer. On the basis of the embedded MWNTs, negatively charged gold
      nanoparticles are anchored to the nanotube surfaces via electrostatic
      interactions between the protonated amino groups and the gold nanoparticles.
      Furthermore, these gold nanoparticles can further grow and magnify along the
      nanotubes through heating in HAuCl4 aqueous solution at 100 degrees C; as a
      result these nanoparticles are joined to form continuous gold nanowires with
      MWNTs acting as templates.

PMID- 16570966
TI  - Synthesis and characterization of indium-doped ZnO nanowires with periodical
      single-twin structures.
AB  - In-doped ZnO (IZO) nanowires have been synthesized by a thermal evaporation
      method. The morphology and microstructure of the IZO nanowires have been
      extensively investigated using scanning electron microscopy (SEM), X-ray
      diffraction (XRD), and high-resolution transmission electron microscopy (HRTEM).
      The products in general contain several kinds of nanowires. In this work, a
      remarkable type of IZO zigzag nanowire with a periodical twinning structure has
      been investigated by transmission electron microscopy (TEM). HRTEM observation
      reveals that this type of IZO nanowire has an uncommonly observed zinc blend
      crystal structure. These nanowires, with a diameter about 100 nm, grow along the
      [111] direction with a well-defined twinning relationship and a well-coherent
      lattice across the boundary. In addition, an IZO nanodendrite structure was also
      observed in our work. A growth model based on the vapor-liquid-solid mechanism is
      proposed for interpreting the growth of zigzag nanowires in our work. Due to the
      heavy doping of In, the emission peak in photoluminescence spectra has red
      shifted as well as broadened seriously.

PMID- 16570967
TI  - Hydrogen capacity of palladium-loaded carbon materials.
AB  - Several samples of palladium-loaded single-wall carbon nanotubes and palladium
      loaded MAXSORB activated carbon were prepared by means of the reaction of the raw
      carbon support with Pd2(dba)3.CHCl3. When carbon nanotubes were used as the
      support, the palladium content in the samples reached 13-31 wt % and fine
      particles of 5-7 nm average size were obtained. In the case of the samples with
      MAXSORB as the support, the palladium content was higher (30-50 wt %) and the
      particle size larger (32-42 nm) than in the nanotube samples. At 1 atm and room
      temperature, the hydrogen capacity of the palladium-loaded samples exceeds 0.1 wt
      % and is much higher than the capacity of the raw carbon supports (less than 0.01
      wt %). The maximum hydrogen capacity at 1 atm and room temperature was found to
      be 0.5 wt %. A maximum hydrogen capacity of 0.7 wt % was obtained at 90 bar in a
      palladium-loaded MAXSORB sample, while the capacities for the raw carbon
      nanotubes and MAXSORB at the same pressure were 0.21 and 0.42 wt %, respectively.
      At low pressure, it was observed that the H/Pd atomic ratios in the palladium
      loaded samples were always higher than in the bulk Pd. The spillover effect is
      considered as a possible cause of the high H/Pd atomic ratios. On the other hand,
      the effect of the pressure increase on the spillover was observed to be very low
      at high pressure and room temperature.

PMID- 16570968
TI  - A simple way to prepare PbS nanocrystals with morphology tuning at room
      temperature.
AB  - A simple way to synthesize PbS nanocrystals with the ability to tune their
      morphology at room temperature is reported. The preparation utilizes an amine
      catalyzed decomposition of a precursor and the amine was found to play dual roles
      as both the catalyst and the capping agent. Spherical PbS nanocrystals of
      diameters 5 to 10 nm were obtained when long chain alkylamines were used in the
      pot. When difunctional ethylenediamine was used instead, exclusively PbS
      dendrites can be isolated from the same precursor at room temperature. Uniform
      six- and four-armed dendrites are observed, with regular branches of
      approximately 20 nm in diameter growing in a parallel order. In a further step,
      morphology tuning of the dendrites to induce 1D growth into nanorods is
      achievable through the addition of a trace amount of stronger capping
      dodecanethiol molecules. Thus, PbS nanorods with aspect ratios of approximately
      20 to 30 could be successfully obtained and illustrated. A possible formation
      mechanism is discussed and the initial step of the reaction mechanism was modeled
      with DFT calculations as a nucleophilic attack.

PMID- 16570969
TI  - Fabrication of ordered catalytically active nanoparticles derived from block
      copolymer micelle templates for controllable synthesis of single-walled carbon
      nanotubes.
AB  - We report the use of the block copolymer micelle approach to produce various
      transition metal nanoparticles such as iron, cobalt, and nickel with precisely
      controlled size and spacing. These uniformly sized catalyst nanoparticles derived
      from the block copolymer micelle approach have enabled the synthesis of carbon
      nanotubes (CNTs) with narrow size distribution. Because of the excellent film
      forming ability of the polymeric material, metal-bearing surface micelles
      produced from the solution micelles can be distributed uniformly on a surface,
      resulting in evenly dispersed catalyst nanoparticles. As a result, high quality
      and uniformly distributed CNTs have been synthesized. Spatially selective growth
      of CNTs from a lithographically patterned metal-bearing micelle film has been
      achieved. The polymer template approach can potentially be extended to synthesize
      single-metallic and bimetallic catalytically active nanoparticles with uniform
      size and spacing and is fully compatible with conventional lithographic process.
      Additionally, catalyst nanoparticles produced from this method do not coalesce at
      high growth temperature. All these attributes make this approach a promising
      fabrication pathway for controllable synthesis of CNTs.

PMID- 16570970
TI  - Photocatalytic activity of structured mesoporous TiO2 materials.
AB  - Starting from colloidal TiO2 nanoparticles in combination with tetraethyl
      orthosilicate using neutral Pluronic or cationic cetyltrimethylammonium as
      templates, a series of structured mesoporous silicas has been obtained. The
      structure of the mesoporous titania was confirmed by isothermal gas adsorption,
      transmission electron microscopy, and X-ray diffraction. The pore diameter ranged
      between 3.8 and 10.9 nm, and the BET surface area varied from 99 to 584 m2 g(-1).
      The photocatalytic activity of these samples for the degradation of phenol in
      aqueous solution has been compared with that of standard P-25 TiO2. Even though
      the activity of these new mesostructured materials is lower that those found for
      P-25 TiO2, the turnover frequency of the photocatalytic activity (moles of phenol
      degraded per Ti atom present at initial reaction time) is much higher for the
      mesoporous titania, particularly with low titanium contents for those materials
      (mpTiO2-5 and TiO2SBA15-5).

PMID- 16570971
TI  - Small fullerenes with BN belts: a density functional theory investigation.
AB  - Density functional calculations have been carried out on a series of BCN hybrid
      fullerenes with certain substitution patterns in comparison with their parent
      compounds Cn (n = 30, 32, 36, 38, 40, 44, 48, 50, 52). The substitutional
      structures, energy gaps between the highest occupied molecular orbital and the
      lowest unoccupied molecular orbital, ionization potentials, electron affinities,
      as well as molecular electrostatic potentials have been systematically
      investigated. The following important points of BCN hybrid fullerenes are
      stressed: The present studied fullerenes, comprising tubular "belt" and polar
      "cap", could be divided into three types of structure; each has different indexes
      of tubular structure and terminal caps. The properties of BCN hybrid fullerenes
      depend on the type of "tubular belt + polar cap" structures, especially, the HOMO
      and LUMO characters and MEPs of BCN fullerene are strongly governed by their
      structure types.

PMID- 16570972
TI  - Adsorption of cyanine dyes on gold nanoparticles and formation of J-aggregates in
      the nanoparticle assembly.
AB  - This paper describes the results of an investigation of the interparticle
      interactions and reactivities in the assembly of gold nanoparticles mediated by
      cyanine dyes. The combination of the positively charged indolenine cyanine dyes
      and the negatively charged gold nanoparticles is shown to form a J-aggregate
      bridged assembly of nanoparticles, in addition to hydrophobic interparticle and
      electrostatic dye-particle interactions. Such interparticle interactions and
      reactivities are studied by probing the absorption of J-aggregates and
      fluorescence from the dyes and the surface plasmon resonance absorption from the
      nanoparticles. The J-aggregation of the dyes adsorbed on the nanoparticles is
      shown to play an important role in the assembly of nanoparticles. The spectral
      evolution of the J-band of the dyes and the surface plasmon resonance band of the
      nanoparticles was found to be sensitive to the nature of the charge and the
      structure of the dyes. The fluorescence quenching for the dyes was shown to be
      quantitatively related to the surface coverage of the dyes on the nanocrystal
      surfaces. These findings have provided important information for assessing a two
      step process involving a rapid adsorption of the dyes on the nanoparticles and a
      subsequent assembly of the nanoparticles involving a combination of interparticle
      J-aggregation and hydrophobic interactions of the adsorbed dyes. The results are
      discussed in terms of the structural effects of the dyes, and the interparticle
      molecular interactions and reactivities, which provide important physical and
      chemical insights into the design of dye-nanoparticle structured functional
      nanomaterials.

PMID- 16570973
TI  - Raman spectra of ionic liquids: a simulation study of AlF3 and its mixtures with
      NaF.
AB  - Theoretical Raman spectra of the melts of NaF/AlF3 mixtures have been obtained
      from computer simulations in order to examine how the Raman spectra reflect the
      coordination structure around the Al3+ ions. The Raman spectra, both polarized
      and depolarized, are calculated from a model for the dependence of the
      polarizability of the system on the ionic coordinates which was inspired by
      electronic structure calculations of the polarizabilities of ions in a condensed
      phase environment. The shapes of the spectra and their evolution with composition
      in the mixtures conform remarkably well to those seen experimentally, and we
      discuss the relationship between the bands seen in the spectra and the
      vibrational modes of the AlFn(3-n) coordination complexes which are found in the
      melts. Finally, we calculate quantities which relate to the degree of cross
      linking between these coordination complexes and their lifetimes.

PMID- 16570974
TI  - Finite element simulations of tip-enhanced Raman and fluorescence spectroscopy.
AB  - Finite element electromagnetic simulations of scanning probe microscopy tips and
      substrates are presented. The enhancement of the scattered light intensity is
      found to be as high as 10(12) for a 20 nm radius gold tip, and tip-substrate
      separation of 1 nm. Molecular resolution imaging (< 1 nm) is achievable, even
      with a relatively large radius tip (20 nm). We also make predictions for imaging
      in aqueous environments, noting a sizable red shift of the spectral peaks.
      Finally, we discuss signal levels, and predict that high-speed Raman mapping
      should be possible with gold substrates and a small tip-substrate separation (< 4
      nm).

PMID- 16570975
TI  - Photoluminescence of Cd1-xMnxS (x < or = 0.3) nanowires.
AB  - Cd1-xMnxS (x = 0.1-0.3) nanowires were synthesized by using the chemical vapor
      deposition method. They all consist of a single-crystalline wurtzite CdS
      structure with a [010] or [011] growth direction. The X-ray diffraction pattern
      reveals the contraction of the lattice constants due to the incorporation of Mn.
      The Mn2+ emission at approximately 2.15 eV, originating from the d-d (4T1 -->
      6A1) transition, appears below 50-80 K. Its decay time is in the range of 0.55-1
      ms, showing a decrease with increasing Mn content. The Mn doping reduces
      significantly the decay time of band-edge emission from 590 ps to 20-30 ps. Upon
      applying magnetic field (up to 7 T), the Mn2+ emission is suppressed and donor
      acceptor pair emission becomes dominant, suggesting the energy transfer from the
      band electrons to the Mn2+ ions.

PMID- 16570976
TI  - Using effusive molecular beams and microcanonical unimolecular rate theory to
      characterize CH4 dissociation on Pt(111).
AB  - The dissociative sticking coefficient for CH4 on Pt(111) has been measured as a
      function of both gas temperature (Tg) and surface temperature (Ts) using effusive
      molecular beam and angle-integrated ambient gas dosing methods. The experimental
      results are used to optimize the three parameters of a microcanonical
      unimolecular rate theory (MURT) model of the reactive system. The MURT
      calculations allow us to extract transition state properties from the data as
      well as to compare our data directly to other molecular beam and thermal
      equilibrium sticking measurements. We find a threshold energy for dissociation of
      E0 = 52.5 +/- 3.5 kJ mol(-1). Furthermore, the MURT with an optimized parameter
      set provides for a predictive understanding of the kinetics of this C-H bond
      activation reaction, that is, it allows us to predict the dissociative sticking
      coefficient of CH4 on Pt(111) for any combination of Ts and Tg even if the two
      are not equal to one another, indeed, the distribution of molecular energy need
      not even be thermal. Comparison of our results to those from recent thermal
      equilibrium catalysis studies on CH4 reforming over Pt nanoclusters (
      approximately 2 nm diam) dispersed on oxide substrates indicates that the
      reactivity of Pt(111) exceeds that of the Pt nanocatalysts by several orders of
      magnitude.

PMID- 16570977
TI  - Effusive molecular beam study of C2H6 dissociation on Pt(111).
AB  - The dissociative sticking coefficient for C2H6 on Pt(111) has been measured as a
      function of both gas temperature (Tg) and surface temperature (Ts) using effusive
      molecular beam and angle-integrated ambient gas dosing methods. A microcanonical
      unimolecular rate theory (MURT) model of the reactive system is used to extract
      transition state properties from the data as well as to compare our data directly
      with supersonic molecular beam and thermal equilibrium sticking measurements. We
      report for the first time the threshold energy for dissociation, E0 = 26.5 +/- 3
      kJ mol(-1). This value is only weakly dependent on the other two parameters of
      the model. A strong surface temperature dependence in the initial sticking
      coefficient is observed; however, the relatively weak dependence on gas
      temperature indicates some combination of the following (i) not all molecular
      excitations are contributing equally to the enhancement of sticking, (ii) that
      strong entropic effects in the dissociative transition state are leading to
      unusually high vibrational frequencies in the transition state, and (iii) energy
      transfer from gas-phase rovibrational modes to the surface is surprisingly
      efficient. In other words, it appears that vibrational mode-specific behavior
      and/or molecular rotations may play stronger roles in the dissociative adsorption
      of C2H6 than they do for CH4. The MURT with an optimized parameter set provides
      for a predictive understanding of the kinetics of this C-H bond activation
      reaction, that is, it allows us to predict the dissociative sticking coefficient
      of C2H6 on Pt(111) for any combination of Ts and Tg even if the two are not equal
      to one another.

PMID- 16570978
TI  - Combination of polarized TIRF and ATR spectroscopies for determination of the
      second and fourth order parameters of molecular orientation in thin films and
      construction of an orientation distribution based on the maximum entropy method.
AB  - This article describes two mathematical formalisms for the determination of the
      second and fourth order parameters of molecular films using optical spectroscopy.
      Method A uses polarized total internal reflection fluorescence (TIRF) to
      calculate the second and fourth order parameters, {P2(cos theta)} and {P4(cos
      theta)}, using an independently determined value for the angle between the
      absorption and emission dipoles, gamma. Method B uses {P2(cos theta)} obtained
      from attenuated total reflectance (ATR) data, along with polarized TIRF
      measurements to calculate {P4(cos theta)} and {cos2 gamma}. The choice of a
      specific method should rely on experimental considerations. We also present a
      method to separate the contributions of substrate surface roughness and dipole
      orientation with respect to the molecular axis from the spectroscopically
      determined second and fourth order parameters. Finally, a maximum entropy
      approach for construction of an orientation distribution from order parameters is
      compared with the commonly used delta and Gaussian distributions.

PMID- 16570979
TI  - Order parameters and orientation distributions of solution adsorbed and
      microcontact printed cytochrome c protein films on glass and ITO.
AB  - The structure of solution adsorbed and microcontact printed (muCP) cytochrome c
      (cyt c) films on glass and indium tin oxide (ITO) was investigated using
      attenuated total reflectance (ATR) and total internal reflectance fluorescence
      (TIRF) spectroscopies to determine the orientation of the heme groups in the
      films. The second and fourth order parameters of the heme as well as information
      on the angle between the absorption and emission dipoles of the heme, gamma, were
      experimentally determined. The order parameters of the heme are related to the
      order parameters of the protein molecule using the known angle between the heme
      plane and the electrostatic dipole moment of the cyt c protein. The effect of the
      surface roughness of the substrates (glass and ITO) was also taken into account
      quantitatively using AFM data. Physically possible order parameters were obtained
      for the heme group in both solution adsorbed and muCP films, but not for the
      electrostatic dipole moment of the protein. In addition, the experimental values
      of {cos2 gamma} for immobilized zinc-substituted cyt c are greater than the
      values of {cos2 gamma} determined in viscous solutions, which could be an
      indication that the environment of the heme groups changes upon adsorption. The
      electron transfer behavior of solution adsorbed and muCP films on ITO, determined
      using electrochemical methods, is compared to their orientation distribution and
      surface coverage as determined by spectroscopic methods.

PMID- 16570980
TI  - Photoassisted adsorption of allylamine and 1-butene on H:Si(111) studied by
      surface vibrational spectroscopies.
AB  - Ultraviolet photoassisted adsorption of terminally double-bonded molecules,
      allylamine (CH2=CH-CH2-NH2) and 1-butene (CH2=CH-CH2-CH3), on hydrogen-terminated
      silicon (111) surface was attempted to obtain adsorbates covalently terminating
      the surface Si atoms. The adsorption process was monitored by high-resolution
      electron energy loss spectroscopy, multiple internal infrared reflection
      absorption spectroscopy, and Auger electron spectroscopy. Allylamine adsorbates
      emerged upon delivery of allylamine gas under ultraviolet irradiation. The N-H
      bonds in allylamine were evidenced to survive over the photoadsorption process by
      vibrational analysis and by the reaction with ketene. CH3- groups were detected
      at low coverage, indicating anchoring of the organic moieties by the secondary
      (sec-) type carbon atoms, which were taken over by the primary (n-) type with
      increasing coverage. C-D bonds were detected after deposition on deuterium
      terminated Si(111) upon incorporation of Si-terminating H into the hydrocarbon
      part of adsorbates. In the case of 1-butene, not only the C=C end but also the
      CH3- end of a molecule might attach on Si, resulting in emergence of adsorbates
      composed of CH2 groups. The newly obtained adsorbates are prospective as a
      material applied for nanolithography, fine electrochemistry, and nano
      biotechnology.

PMID- 16570982
TI  - Catalyst-assisted formation of nanocantilever arrays on ZnS nanoribbons by post
      annealing treatment.
AB  - Nanocantilever arrays were formed on the edges of the +/- (0001) planes of pre
      synthesized ZnS nanoribbons via catalyst-assisted post-annealing treatment on Si
      substrate at 600 degrees C. Similar nanostructures could also be generated when
      ZnS nanoribbons were annealed by mixing with Si or SiO powder. The formation of
      nanocantilever arrays is associated with orientation-dependent chemical etching
      of the +/- (0001) polar surfaces of ZnS nanoribbons. The ability of increasing
      structural complexity beyond the one-step "thermal evaporation and condensation"
      synthesis provides a new dimension to the rational design of building blocks for
      nanodevices.

PMID- 16570981
TI  - A unified single-event microkinetic model for alkane hydroconversion in different
      aggregation states on Pt/H-USY-zeolites.
AB  - A single-event microkinetic model for the catalytic hydroconversion of
      hydrocarbons on Pt/H-US-Y bifunctional zeolite catalysts developed for low
      pressure vapor phase conditions was extended to cover high-pressure vapor phase
      and liquid phase conditions. The effect of the density of the bulk hydrocarbon
      phase on the physisorption as well as on the protonation steps of the reaction
      network was accounted for explicitly and can be interpreted in terms of
      "compression" of the hydrocarbon sorbate inside the zeolite pores and "solvation"
      of the catalyst framework by the dense bulk hydrocarbon phase. The bulk phase
      density effect on the physisorbed state is described via a single excess free
      enthalpy of physisorption. A dense bulk hydrocarbon phase destabilizes the
      sorbate molecules inside the catalyst pores. An expression of the excess free
      enthalpy of physisorption involving the fugacity coefficient and a zeolite
      dependent factor allows description of physisorption data. Typical excess free
      enthalpy values are in the range 1.5-5.1 kJ mol(-1) increasing with carbon number
      in the series of C5-C16 alkanes. At high-pressure vapor phase and liquid phase
      conditions, the excess standard protonation enthalpy is estimated at -7.8 kJ mol(
      1) leading to relatively more stable carbenium ions at dense bulk phase
      conditions. As a result of the excess physisorption and protonation properties,
      the lightest hydrocarbons in mixtures are more competitive at dense phase
      conditions and their conversion is enhanced compared to low-density conditions.

PMID- 16570983
TI  - Influence of V content on the nature and strength of acidic sites in VSibeta
      zeolite evidenced by IR spectroscopy.
AB  - VSibeta zeolites prepared by a two-step postsynthesis method have been
      characterized by physical techniques. A significant reduction of intensity of the
      IR band near 3515 cm(-1) after impregnation of dealuminated beta zeolite with
      aqueous NH4VO3 indicates that V ions specifically react with hydrogen-bonded SiO
      H groups of vacant T sites. IR bands at 3618 and 3645 cm(-1) are assigned to SiO
      H groups interacting with V and to VO-H groups, respectively. In VSibeta, diffuse
      reflectance UV-visible data show that below 1.9 wt % V is present as lattice
      tetrahedral species and at higher content as extra-lattice octahedral species
      (mononuclear and polynuclear). VSibeta samples are EPR-silent at 298 or 77 K
      suggesting that there are no paramagnetic VIV ions. IR studies show that V-OH
      groups are less acidic than Si-OH-Al groups of parent HAlbeta zeolite. IR results
      of CO adsorption evidence three kinds of Lewis acidic sites, related to lattice
      mononuclear and extra-lattice mononuclear and polynuclear V species. Quantitative
      IR studies of ammonia and pyridine adsorption reveal that only about half of V
      introduced into zeolite is able to form either Bronsted or Lewis acidic sites.

PMID- 16570984
TI  - Reversible association of thermoresponsive gold nanoparticles: polyelectrolyte
      effect on the lower critical solution temperature of poly(vinyl methyl ether).
AB  - Thermoresponsive gold nanoparticles (GNPs) have been prepared by the borohydride
      reduction of gold salt in the presence of water-soluble polymer, poly(vinyl
      methyl ether) (PVME). The PVME-coated GNPs (PVME-GNPs) have been assembled into
      large aggregates in the presence of polyelectrolytes, viz., poly(sodium-4 styrene
      sulfonate) and sodium salt of carboxymethylcellulose at low pH by raising the
      solution temperature from 20 to 40 degrees C. Increase of temperature triggers
      the interparticle association due to hydrophobic interaction of pendent methyl
      group of the surface adsorbed PVME. This assembly process is reversible with
      respect to temperature and pH of the medium and was studied by monitoring the
      change in surface plasmon resonance band of PVME-GNPs. Three-dimensional
      assemblies of various architectures, depending on the concentration of
      polyelectrolytes, were observed through transmission electron microscopy. A
      mechanistic model has been suggested for the reversible assembly formation that
      suits well with the experimental observations. The changes in optical properties
      of the PVME-GNPs due to their aggregation/disaggregation enabled us to use it as
      an effective tool to monitor the change in lower critical solution temperature
      (LCST) of PVME in the presence of polyelectrolytes due to interpolymer
      complexation at low pH. This result agrees well with the variation of LCST of
      pure aqueous PVME solution in the presence of polyelectrolytes measured by
      conventional turbidimetric technique.

PMID- 16570985
TI  - High frequency faradaic rectification voltammetry at microelectrodes.
AB  - An experimental setup for carrying out faradaic rectification measurements at
      micrometer-sized electrodes under potential control is described. A new method of
      data analysis is proposed that allows the determination of the standard rate
      constant and the electron-transfer coefficient of a fast charge transfer process
      without knowing the impedance of the microelectrode. This method is based on the
      frequency dependence of the shape of the faradaic rectification voltammograms
      (i.e., the average width of the peaks and the ratio of the peak heights) rather
      than on the magnitude of the faradaic rectification signal. The method was tested
      in the determination of heterogeneous electron transfer kinetics of Fe(CN)6(3-/4
      ) and Ru(NH3)6(2+/3+) in aqueous solutions on a platinum microelectrode (12.5
      microm in radius) and ferrocene/ferrocinum redox couple in a dimethylformamide
      solution on a gold microelectrode (12.5 microm in radius).

PMID- 16570986
TI  - Electroreduction of aromatic oximes: diprotonation, adsorption, imine formation,
      and substituent effects.
AB  - Aromatic oximes are reduced in aqueous solution in a four-electron process. The
      reducible species in the pH range 5-8 is a diprotonated form of the oxime. This
      species is generated in the course of electrolysis in the vicinity of the
      electrode surface from the adsorbed neutral form of the oxime. The reduction is
      initiated by a cleavage of the N-O bond. The diprotonation facilitates the
      reduction process by the preformation of OH2+ as a good leaving group and by a
      positive charge on the azomethine nitrogen. Diprotonation has been proven based
      on shapes of i = f(pH) plots, by observed shifts of half-wave potentials with pH
      and by comparison with the reduction of nitrones. Some observed deviations from
      theoretical i = f(pH) plots were attributed to the role of adsorption on the rate
      of protonation. Adsorption is also responsible for dips on some of the i-E
      curves. Adsorption plays a role at concentrations as low as 1 x 10(-5) M, when
      the electrode surface is still not fully covered. This indicates that catalyzed
      protonation occurs on islets of adsorbed materials. At pH 2-5 the studied oximes
      in the vicinity of the electrode are predominately present in a protonated form,
      which is less strongly adsorbed. In this pH range the protonation takes place in
      a homogeneous reaction layer of the electrode. It yields a monoprotonated form,
      which is reduced. The separation of two two-electron waves observed for some
      oximes in acidic media serves as an experimental proof of the formation of imines
      as reduction intermediates. This separation is caused by the differences in pKa
      values of protonated forms of oximes and imines. The effects of substituents in
      the para position on the benzene ring are characterized by correlation with the
      Hammett substituent constant sigmax. This has been proven at pH 1.5 for
      substituted benzaldehyde oximes and at pH 5.0 for substituted acetophenone
      oximes.

PMID- 16570987
TI  - Temperature-dependent anti-stokes/stokes ratios under surface-enhanced Raman
      scattering conditions.
AB  - We make systematic measurements of Raman anti-Stokes/Stokes (aS/S) ratios using
      two different laser excitations (514 and 633 nm) of rhodamine 6G (RH6G) on dried
      Ag colloids over a wide range of temperatures (100 to 350 K). We show that a
      temperature scan allows the separation of the contributions to the aS/S ratios
      from resonance effects and heating/pumping, thus decoupling the two main aspects
      of the problem. The temperature rise is found to be larger when employing the 633
      nm laser. In addition, we find evidence for mode specific vibrational pumping at
      higher laser power densities. We analyze our results in the framework of ongoing
      discussion on laser heating/pumping under surface-enhanced Raman scattering
      (SERS) conditions.

PMID- 16570988
TI  - Wavelength-sensitive photocatalytic degradation of methyl orange in aqueous
      suspension over iron(III)-doped TiO2 nanopowders under UV and visible light
      irradiation.
AB  - Well-crystallized iron(III)-doped TiO2 nanopowders with controlled Fe3+ doping
      concentration and uniform dopant distribution, have been synthesized with plasma
      oxidative pyrolysis. The photocatalytic reactivity of the synthesized TiO2
      nanopowders with a mean particle size of 50-70 nm was quantified in terms of the
      degradation rates of methyl orange (MO) in aqueous TiO2 suspension under UV
      (mainly 365 and 316 nm) and visible light irradiation (mainly 405 and 436 nm).
      The photodecomposition of MO over TiO2 nanopowders followed a distinct two-stage
      pseudo first order kinetics. Interestingly, the photocatalytic reactivity depends
      not only on the iron doping concentration but also on the wavelength of the
      irradiating light. Under UV irradiation, nominally undoped TiO2 had much higher
      reactivity than Fe3+ -doped TiO2, suggesting that Fe3+ doping (> 0.05 at. %) in
      TiO2 with a mean particle size of approximately 60 nm was detrimental to the
      photocatalytic decomposition of methyl orange. Whereas, under visible light
      irradiation, the Fe3+ -doped TiO2 with an intermediate iron doping concentration
      of approximately 1 at. % had the highest photocatalytic reactivity due to the
      narrowing of band gap so that it could effectively absorb the light with longer
      wavelength. A strategy for improving the photocatalytic reactivity of Fe3+ -doped
      TiO2 used in the visible light region is also proposed.

PMID- 16570989
TI  - Novel core-shell-structured Li[(Ni0.8Co0.2)0.8(Ni0.5Mn0.5)0.2]O2 via
      coprecipitation as positive electrode material for lithium secondary batteries.
AB  - We have successfully synthesized a spherical core-shell structure based on
      Li[(Ni0.8Co0.2)0.8(Ni0.5Mn0.5)0.2]O2 via a coprecipitation route. According to
      the careful examination by scanning electron microscopy (SEM), transmission
      electron microscopy energy-dispersive spectroscopy (TEM-EDS), and X-ray
      diffraction (XRD), it was found that the core-shell particle consisted of
      Li[Ni0.8Co0.2]O2 as the core and Li[Ni0.5Mn0.5]O2 as the shell, of which the
      thickness was estimated to be 1 to approximately 1.5 microm. Both the core and
      shell were dense as confirmed by SEM. Though the core-shell-structured
      Li[(Ni0.8Co0.2)0.8(Ni0.5Mn0.5)0.2]O2 delivered a slightly reduced initial
      discharge capacity, the capacity retention and thermal stability were
      significantly improved relative to those of the Li[Ni0.8Co0.2]O2 electrode
      without the Li[Ni0.5Mn0.5]O2 shell. The carbon/Li[Ni0.8Co0.2]O2 pouch cell
      underwent an explosive ignition during the nail penetration test, whereas the
      carbon/Li[(Ni0.8Co0.2)0.8(Ni0.5Mn0.5)0.2]O2 cell remained stable, demonstrating
      the superior thermal stability of the core-shell electrode. As a new positive
      electrode material, the core-shell-structured
      Li[(Ni0.8Co0.2)0.8(Ni0.5Mn0.5)0.2]O2 is a significant breakthrough in the
      development of high-capacity lithium secondary batteries.

PMID- 16570990
TI  - Temperature dependence of the field effect mobility of solution-grown germanium
      nanowires.
AB  - The temperature dependence of the field effect mobility was measured for solution
      grown single-crystal Ge nanowires. The nanowires were synthesized in hexane from
      diphenylgermane by the supercritical fluid-liquid-solid process using gold
      nanocrystals as seeds. The nanowires were chemically treated with isoprene to
      passivate their surfaces. The electrical properties of individual nanowires were
      then measured by depositing them on a Si substrate, followed by electrical
      connection with Pt wires using focused ion beam assisted chemical vapor
      deposition. The nanowires were positioned over TaN or Au electrodes covered with
      ZrO2 dielectric that were used as gates to apply external potentials to modulate
      the conductance. Negative gate potentials increased the Ge nanowire conductance,
      characteristic of a p-type semiconductor. The temperature-dependent source/drain
      current-voltage measurements under applied gate potential revealed that the field
      effect mobility increased with increasing temperature, indicating that the
      carrier mobility through the nanowire is probably dominated either by a hopping
      mechanism or by trapped charges in fast surface states.

PMID- 16570991
TI  - Distribution, structure, and dynamics of cesium and iodide ions at the H2O-CCl4
      and H2O-vapor interfaces.
AB  - Molecular dynamics simulations utilizing many-body potentials of H2O-CCl4 and H2O
      vapor interfaces were carried out at different cesium and iodide ion
      concentrations to compare ion distribution, interfacial orientational and
      structural properties, and dynamics. It was found that cesium was repelled by
      both interfaces, and iodide was active at both interfaces, but to a much greater
      degree at the H2O-vapor interface. At the interface, the iodide dipole was
      strongly induced, orienting perpendicular to the interface for both systems,
      leading to stronger hydrogen bonds with water. For the H2O-CCl4 interface,
      though, there was a compensation between these strong hydrogen bonds and short to
      moderate ranged repulsion between iodide and CCl4. Hydrogen bond distance and
      angular distributions showed weaker water-water hydrogen bonds at both
      interfaces, but generally stronger water-iodide hydrogen bonds. Both
      translational and rotational dynamics of water were faster at the interface,
      while for CCl4, its translational dynamics was slower, but rotational dynamics
      faster at the interface. For many of the studied systems and species,
      translational diffusion was found to be anisotropic at both interfacial and bulk
      regions.

PMID- 16570992
TI  - Understanding gold-thiolate cluster emission from self-assembled monolayers upon
      kiloelectronvolt ion bombardment.
AB  - This article focuses on the emission of organometallic clusters upon
      kiloelectronvolt ion bombardment of self-assembled monolayers. It is particularly
      relevant for the elucidation of the physical processes underlying secondary ion
      mass spectrometry (SIMS). The experimental system, an overlayer of octanethiols
      on gold, was modeled by classical molecular dynamics, using a hydrocarbon
      potential involving bonding and nonbonding interactions (AIREBO). To validate the
      model, the calculated mass and energy distributions of sputtered atoms and
      molecules were compared to experimental data. Our key finding concerns the
      emission mechanism of large clusters of the form MxAuy up to M6Au5 (where M is
      the thiolate molecule), which were not observed under sub-kiloelectronvolt
      projectile bombardment. Statistically, they are predominantly formed in high
      yield events, where many atoms, fragments, and (supra)molecular species are
      desorbed from the surface. From the microscopic viewpoint, these high-yield
      events mostly stem from the confinement of the projectile and recoil atom
      energies in a finite microvolume of the sample surface. As a result of the high
      local energy density, molecular aggregates desorb from an overheated liquidlike
      region surrounding the impact point of the projectile.

PMID- 16570993
TI  - Chemical structure and orientation of ethylene on Si(114)-(2 x 1)/c(2 x 2).
AB  - The basic chemical structure and orientation of ethylene chemisorbed on Si(114)
      (2 x 1) at submonolayer coverage is characterized in ultrahigh vacuum using
      transmission Fourier transform infrared (FTIR) spectroscopy. The spectra are
      consistent with di-sigma bonding of ethylene to the surface with a preferential
      molecular orientation over macroscopic lengths. These results are supported by
      density functional theory (DFT) calculations of vibrational frequencies for
      optimized ethylene-Si(114) structures occupying the dimer and rebonded atom
      surface sites. A detailed analysis of the strong angular and polarization
      dependence of the C-H stretching mode intensities is also consistent with the
      adsorption structures identified by DFT, indicating that ethylene chemisorbs with
      the C-C bond axis parallel to the structural rows oriented along the [10]
      direction on the Si(114)-(2 x 1) surface. The results indicate that the unique
      structure of this surface makes it an excellent template for elucidating
      relationships between surface structure and organic reaction mechanisms on
      silicon.

PMID- 16570994
TI  - Single-component and mixed ferrocene-terminated alkyl monolayers covalently bound
      to Si(111) surfaces.
AB  - Self-assembled ferrocene monolayers covalently bound to monocrystalline Si(111)
      surfaces have been prepared from the attachment of an amine-substituted ferrocene
      derivative to a pre-assembled acid-terminated alkyl monolayer using carbodiimide
      coupling. This derivatization strategy yielded nanometer-scale clean, densely
      packed monolayers, with the ferrocene units being more than 20 A from the
      semiconductor surface. The amount of immobilized electroactive units could be
      varied in the range 2 x 10(-11) to approximately 3.5 x 10(-10) mol cm(-2) by
      diluting the ferrocene-terminated chains by inert n-decyl chains. The highest
      coverage obtained for the single-component monolayer corresponded to 0.25-0.27
      bound ferrocene per surface silicon atom. The electrochemical characteristics of
      the mixed n-decyl/ferrocene-terminated monolayers were found to not depend
      significantly on the surface coverage of ferrocene units. The reversible one
      electron wave of the ferrocene/ferrocenium couple was observed at E degrees ' =
      0.50 +/- 0.01 V vs SCE, and the rate constant of electron transfer kapp was about
      50 s(-1).

PMID- 16570995
TI  - Rational design of selective, sulfur-resistant oxidation emissions catalysts.
AB  - A new catalyst design strategy based on optimizing electronic structure has been
      proposed and then applied to a very important environmental application, the
      design of selective, sulfur-resistant oxidation emissions catalysts. The modified
      d-band center model developed by us in a previous study, together with an energy
      decomposition scheme, is used to correlate measures of reactivity with reaction
      barriers of SO2 + O --> SO3 and NO + O --> NO2 on surfaces. Our objective is to
      find a catalyst which is active in oxidizing NO to NO2 but relatively inactive in
      oxidizing SO2 to SO3. The Ir alloyed Pt(111) surface is found to have the highest
      selectivity for oxidation of NO over SO2 at 700 K. Unfortunately, there is a
      slope change in the correlation of the weighted d-band center with the adsorption
      of NO at the transition state, which narrows down the range of the theoretical
      selectivity. Our ongoing study aims at understanding the reason for this. The
      general importance of this study for surface catalysis is also discussed.

PMID- 16570996
TI  - Molecular dynamics study of the molecular weight dependence of surface tensions
      of normal alkanes and methyl methacrylate oligomers.
AB  - Surface tensions (gamma) of normal alkanes and methyl methacrylate (MMA)
      oligomers at various molecular weights in the low molecular weight range were
      computed using a newly proposed molecular dynamics (MD) simulation strategy which
      was developed based on the definition of gamma = ( partial differential U/
      partial differential sigma)n,V,S. The MD simulations, even with the use of a
      generic force field, reproduced the experimentally observed molecular weight
      dependence of gamma (i.e., gamma proportional Mn(-2/3), where Mn is the number
      average molecular weight) for both series of oligomers. Analysis of the data
      reveals that solvent accessible surface area, one of the key input variables used
      for the calculation of gamma, exhibits an Mn(2/3) (rather than Mn(1)) dependence.
      The reason for such dependence is that solvent accessible surface area formed by
      the chainlike small molecules depends, to a larger extent, on their orientations
      rather than their size. However, this is not the case for high molecular weight
      molecules as solvent accessible surface area of such surfaces are determined by
      the orientations of their segments which are determined by the conformations of
      the molecules. This may explain why surface tension of polymers experimentally
      exhibits an Mn(-1) dependence. It is inferred that the corresponding molecular
      weight dependence of the entropy changes associated with molecules in the low and
      high molecular weight ranges would be different.

PMID- 16570997
TI  - Optical and physical properties of cobalt oxide films electrogenerated in
      bicarbonate aqueous media.
AB  - For the first time, cobalt oxide films that are highly protective against
      localized corrosion and depicting a wide variety of bright and uniform colors due
      to light interference, have been successfully electrogenerated on polycrystalline
      cobalt disk electrodes under potentiostatic polarization in a mild aqueous
      bicarbonate medium. Open circuit potential measurements have shown the formation
      of a film with a bilayered structure, organized as a thin Co3O4 outer layer and a
      thick CoO inner layer. The existence of Co3O4 as a thin outer layer, previously
      postulated from galvanostatic reduction experiments, has been confirmed from XPS
      analysis. Raman spectroscopy, performed using a very low laser intensity, has
      shown that the films are mainly composed of CoO. The broadness of the Raman bands
      observed is associated to the amorphous character of the film, a result that has
      been confirmed by spectroscopic ellipsometry and X-ray diffraction analysis.
      Overall film thicknesses, well controlled by the anodization duration, were
      determined and correlated using mechanical (atomic force microscopy and
      profilometry) and spectroscopic (specular UV-vis-NIR reflectance and
      ellipsometry) techniques. Spectroscopic ellipsometry, using a simple amorphous
      dispersion model, has proved efficient for measuring thicknesses of films ranging
      from 31 to 290 nm with very low standard deviations. The real part of the complex
      refractive indices of these films, ranging from 1.8 to 2.2 (at lambda = 632.8 nm)
      depending on the anodization duration, is in good agreement with values reported
      in the literature for CoO. The film with the highest refractive index, and
      consequently the more densely packed structure, was obtained following a 30
      minute anodization period.

PMID- 16570998
TI  - Synthesis and structural characterization of Se-modified carbon-supported Ru
      nanoparticles for the oxygen reduction reaction.
AB  - This work is part of a continued research aimed at the understanding of the
      promoting role of Se in the enhancement of the electrocatalytic activity of Ru in
      the oxygen reduction reaction. The objective of this paper is to systematically
      investigate the transformation of Ru nanoparticles upon their modification with
      the increasing amounts of Se. The Se-modified Ru/C samples with Se:Ru ratio from
      0 to 1 were prepared by reacting carbon-supported Ru nanoparticles with SeO2
      followed by reductive annealing and characterized using high-resolution
      transmission electron microscopy, energy-dispersive X-ray, X-ray diffraction
      analysis, X-ray photoelectron spectroscopy, and extended X-ray absorption fine
      structure. The results suggest that Se strongly interacts with Ru, resulting in
      the chemical bond between Ru and Se and formation of Ru selenide clusters whose
      core at low Se content can be described as Ru2Se2O0.5. At Se:Ru = 1, high
      resolution electron microscopy shows evidence of formation of core-shell
      particles, comprising a hexagonally packed Ru core and a Ru selenide shell with
      lamellar morphology. Modification of Ru nanoparticles with Se enhances their
      electrocatalytic activity in the oxygen reduction reaction, which is explained by
      the role of Se in inhibiting surface oxidation.

PMID- 16570999
TI  - Photophysics of PTCDA and Me-PTCDI thin films: effects of growth temperature.
AB  - The effect of deposition temperature on the photophysical properties of 3,4,9,10
      perylenetetracarboxylic dianhydride (PTCDA) and N,N'-dimethylperylene-3,4,9,10
      bis(dicarboximide) (Me-PTCDI) films is investigated with steady-state and time
      resolved spectroscopy. Atomic force microscopy (AFM) images of the film surfaces
      show an increase in the dimensions of crystallites with substrate temperature,
      culminating in the formation of elongated crystallites on substrates held close
      to the sublimation temperature. In contrast, despite an improvement in the
      crystal quality, X-ray diffraction (XRD) studies indicate that the substrate
      temperature has a negligible effect on the molecular orientation; the PTCDA and
      Me-PTCDI molecules align parallel and tilted to the substrate surface,
      respectively. Both materials exhibit characteristic absorption, due to mixing
      between charge-transfer and Frenkel species, and broad structureless
      photoluminescence. Growth at elevated temperatures gives rise to increased low
      energy absorption, attributed to the formation of charge-transfer species, and
      enhanced blue-shifted emission, although the effects are less pronounced for Me
      PTCDI. Time-correlated single-photon counting data indicate that the enhancement
      coincides with a lengthening of the fluorescence decays, over the whole emission
      spectrum.

PMID- 16571000
TI  - Nitro group as a means of attaching organic molecules to silicon: nitrobenzene on
      Si(100)-2 x 1.
AB  - This paper will present the computational and experimental infrared studies of
      the reactions of nitrobenzene on a Si(100) surface, a prototypical model reaction
      for understanding the behavior of bifunctional molecules on semiconductor
      surfaces. The initial reaction of nitrobenzene with the Si(100)-2 x 1 occurs via
      1,3-dipolar cycloaddition of the nitro group to the silicon surface dimer.
      Computational exploration of the initial adsorption configurations suggests that
      two stable structures can be formed: one with the phenyl ring essentially
      perpendicular to the surface; the other one with the tilt angle of approximately
      113 degrees with respect to the surface normal. The barrier for converting the
      latter into the former, more stable by approximately 13 kJ/mol, is 19.1 kJ/mol.
      Further thermal reactions are analyzed, and the reaction pathways are compared
      for the computational models with fixed vs relaxed subsurface silicon atoms.
      While all the surface species resulting from nitrobenzene transformations on the
      Si(100)-2 x 1 surface studied here are thermodynamically stable, most of the
      reaction pathways can be ruled out on the basis of the analysis of the transition
      states leading to these species and on the comparison of predicted and measured
      vibrational spectra. As a result, the exact adsorption configurations can be
      pinpointed.

PMID- 16571001
TI  - A first-principles study of the electronic structure and stability of a lithium
      aluminum hydride for hydrogen storage.
AB  - LiAlH4 holds great promise for reversible hydrogen storage, where a fundamental
      understanding of hydrogen interaction with the metal elements is essential to
      further improve its properties. The present paper reports a first-principles
      study of its stability and electronic structure, using a full potential
      linearized augmented plane wave (FLAPW) method within the generalized gradient
      approximation (GGA) for high accuracy. The theoretically calculated heat of
      formation agrees well with experiment. The electronic structures show that the H
      atoms bond nonequivalently with the Al in the [AlH4]- ligand, which leads to
      complex dehydrogenation characteristics of LiAlH4.

PMID- 16571002
TI  - Distillation kinetics of solid mixtures of hydrogen peroxide and water and the
      isolation of pure hydrogen peroxide in ultrahigh vacuum.
AB  - We present results of the growth of thin films of crystalline H2O2 and H2O2*2H2O
      (dihydrate) in ultrahigh vacuum by distilling an aqueous solution of hydrogen
      peroxide. We traced the process using infrared reflectance spectroscopy, mass
      loss on a quartz crystal microbalance, and in a few cases ultraviolet-visible
      reflectance. We find that the different crystalline phases-water, dihydrate, and
      hydrogen peroxide-have very different sublimation rates, making distillation
      efficient to isolate the less volatile component, crystalline H2O2.

PMID- 16571004
TI  - Further test of third order + second-order perturbation DFT approach: hard core
      repulsive Yukawa fluid subjected to diverse external fields.
AB  - Grand canonical Monte Carlo simulation is used to investigate density profiles of
      hard-core repulsive Yukawa (HCRY) model fluid under the influence of various
      external fields and radial distribution function (RDF) of the bulk HCRY system.
      The aim of these extensive simulations is to provide exact data for purely
      repulsive interaction potential against which the validity of a third order +
      second-order perturbation DFT approach can be tested. It is found that a
      semiempirical parametrized bridge function due to Malijevsky and Labik performs
      very well for the RDF of the bulk HCRY fluid. Incorporation of a bulk second
      order direct correlation function (DCF) of the HCRY fluid based on the Malijevsky
      Labik bridge function into the third order + second-order perturbation DFT
      approach yields the resulting theoretical predictions for the density profiles of
      inhomogeneous HCRY fluid that are in a very good agreement with the simulation
      data, an exception being somewhat larger deviations appearing for the structure
      of the fluid around the center of a hard spherical cavity. Both theory and
      simulation predict layering transition and gas-liquid coexistence phenomena
      occurring with the HCRY model fluid under confined conditions. For the case of an
      inverse sixth-power repulsive potential under the influence of a flat stationary
      wall defined by an inverse twelfth-power repulsive potential, the present third
      order + second-order perturbation DFT approach is found to be superior to several
      existing weighted density approximations (WDA) and partitioned WDA.

PMID- 16571005
TI  - PVTx measurements of the N-methylpyrrolidone/methanol mixed solvent: cubic and
      SAFT EOS analyses.
AB  - The PVTx behavior for the x N-methylpyrrolidone (NMP) + (1 - x) methanol
      compressed liquid solvent is reported over the full composition range and within
      wide pressure and temperature ranges. The derived excess properties were analyzed
      in terms of structural effects and intermolecular interactions and revealed
      strong H-bonding heteroassociations between the two components. The cubic
      equations of state by Soave (SRK), Peng-Robinson (PR), Patel-Teja (PT), and Sako
      Wu-Prausnitz (SWP), and the statistical associating fluid theory (SAFT) equation
      of state, combined with a number of selected mixing rules, were used to correlate
      and predict the behavior of both the pure components and mixed solvent. While the
      classical cubic equations of state were not successful in describing the
      properties of this system, the SWP equation of state and the SAFT yielded
      reasonably good results.

PMID- 16571006
TI  - Diffusion and cluster formation in one-dimensional systems with attractive
      interactions.
AB  - We study cluster formation in a finite one-dimensional model system where the
      particles experience long-range attractive forces. The particles are first placed
      in equidistant positions by a repulsive potential, which then is turned off, and
      only a weak long-range potential acts between the particles. It is shown that the
      mean-square deviation in distance between the colloids at first increases due to
      normal Brownian motion, followed by a crossover to anomalous diffusion governed
      by the long-range forces. Moreover, we also found that the subsequent cluster
      formation could be described by a Poisson distribution. The results presented
      here may help us understand diffusion and cluster formation in one-dimensional
      systems.

PMID- 16571003
TI  - Interfacial properties of cyclic hydrocarbons: a Monte Carlo study.
AB  - The Monte Carlo technique is used to study the vapor-liquid interface of
      cyclopentane, cyclohexane, and benzene. The OPLS and TraPPE potential fields are
      compared in the temperature range from 298.15 to 348.15 K (273.15-298.15 K for
      C5H10). A new method for the treatment of the long-range interactions in
      inhomogeneous simulations is used. When this new method is employed, the obtained
      values of saturated liquid density and of enthalpy of vaporization are equal to
      those obtained using the bulk isothermal-isobaric Monte Carlo technique. The
      values of surface tension become independent of the cutoff distance and they are
      significantly larger than those when only simple spherical truncation of
      intermolecular interactions is used.

PMID- 16571007
TI  - From surface self-assembly to crystallization: prediction of protein
      crystallization conditions.
AB  - A new criterion based on surface and volume diffusion kinetics was established to
      predict protein crystallization. Similar to the layer-by-layer crystal growth
      process of protein, the kinetics of the two-dimensional self-assembly of protein
      at the aqueous solution surface provides a convenient and reliable way to
      estimate the surface integration and the volume transport during protein
      crystallization. Both the surface and diffusion kinetics were estimated based on
      the protein self-assembly at the air/solution interface, which can be obtained by
      measuring the surface tension. A crystallization coefficient is found to provide
      an effective and reliable criterion to predict protein crystallization
      conditions. This criterion has been applied to lysozyme, concanavalin A and BSA
      crystallization, and it turns out to be very successful and more reliable than
      the second virial coefficient criterion.

PMID- 16571008
TI  - Electronic transitions of the Soret band of reaction centers from Rhodobacter
      sphaeroides studied by femtosecond transient absorbance spectroscopy.
AB  - The Soret band of reaction centers from Rhodobacter sphaeroides has been
      systematically studied using femtosecond transient absorption spectroscopy. When
      the excitation wavelength was scanned over the entire Soret band, the approximate
      absorption spectra of the bacteriochlorophyll dimer, the monomer
      bacteriochlorophylls, and the bacteriopheophytins within the Soret band were
      determined by analyzing the ground state bleaching with about 100 fs resolution.
      The main contribution of H is on the blue end of the spectrum, peaking near 350
      nm, P absorbs mostly on the red side of the spectrum, but probably has multiple
      bands, and the main absorbance of B likely lies between H and P, overlapping with
      P on the red side (particularly near 390 nm). The energy transfer from B to P in
      the QY band takes about 300 fs when Soret-band excitation is used and the time
      constant of overall energy transfer from H to B to P in the QY band when H is
      specifically excited near 350 nm is about 500 fs. Internal conversion after Soret
      band excitation is the rate-limiting step for the energy-transfer process. The
      time constant of internal conversion for B and P is less than 300 fs, and for H
      it is about 500 fs.

PMID- 16571009
TI  - Unfolding of G-quadruplexes: energetic, and ion and water contributions of G
      quartet stacking.
AB  - It has been shown that DNA oligonucleotides composed, in part, of G repeat
      sequences can adopt G-quadruplex structures in the presence of specific metal
      ions. In this work, we use a combination of spectroscopic and calorimetric
      techniques to determine the spectral and thermodynamic characteristics of two DNA
      aptamers, d(G2T2G2TGTG2T2G2), G2, and d(G3T2G3TGTG3T2G3), G3; a sequence in the
      promoter region of the c-MYC oncogene, d(TG4AG3TG4AG3TG4A2G2), NHE-III; and the
      human telomere sequence d(AG3T2AG3T2AG3T2AG3), 22GG. The circular dichroism
      spectra of these oligonucleotides in the presence of K+ indicate that all form G
      quadruplexes with G-quartets in an antiparallel arrangement (G2), in a parallel
      arrangement (NHE-III and 22GG), or in a mixed parallel and antiparallel G-quartet
      arrangement (G3). Melting profiles show transition temperatures, TM, above 45
      degrees C that are independent of strand concentration, consistent with the
      formation of very stable intramolecular G-quadruplexes. We used differential
      scanning calorimetry to obtain complete thermodynamic profiles for the unfolding
      of each quadruplex. Subtracting the thermodynamic folding profiles of G2 from
      those of G3 yielded the following thermodynamic profile for the formation of a G
      quartet stack: DeltaG degrees 20 = -2.2 kcal/mol, DeltaHcal = -14.6 kcal/mol,
      TDeltaScal = -12.4 kcal/mol, DeltanK+ = -0.3 mol of K+/mol, and DeltanW = 13 mol
      of H2O/mol. Furthermore, we used this profile to estimate the thermodynamic
      contributions of the loops and/or extra base sequences of each oligonucleotide in
      the G-quadruplex state. The average free energy contributions of the latter
      indicate that the incorporation of loops and base overhangs stabilizes quadruplex
      structures. This stabilization is enthalpy-driven and is due to base-stacking
      contributions.

PMID- 16571010
TI  - Separating structural heterogeneities from stochastic variations in fluorescence
      resonance energy transfer distributions via photon distribution analysis.
AB  - We establish a probability distribution analysis (PDA) method for the analysis of
      fluorescence resonance energy transfer (FRET) signals to determine with high
      precision the originating value of a shot-noise-limited signal distribution. PDA
      theoretical distributions are calculated explicitly including crosstalk,
      stochastic variations, and background and represent the minimum width that a FRET
      distribution must have. In this way an unambiguous distinction is made between
      shot-noise distributions and distributions broadened by heterogeneities. This
      method simultaneously and effectively extracts highly resolved information from
      FRET distributions. The theoretical histograms match the exact profile of
      histograms generated from constant transfer efficiency experimental data with a
      chi2 near unity. The chi2 surface suggests an ultimate level of precision with
      FRET of < 1% of the Forster radius. Distributions of FRET signals in donor
      acceptor-labeled DNA were unambiguously identified as being broader than shot
      noise variations could explain. A model describing a Gaussian distribution of
      distances was tested with the PDA method and demonstrated 5 A inhomogeneities due
      to dye motions. The capability of this method to recover quantitative information
      from FRET distributions has potential applications for studying molecular
      conformations and dynamics. Potential sources for artifacts such as acceptor
      photobleaching, spectrally different observation volumes, and fluctuations of the
      Forster radius are ruled out.

PMID- 16571012
TI  - Energy transfer from adenosine triphosphate.
AB  - We suggest a direct molecular mechanism of energy transfer from adenosine
      triphosphate (ATP) in hydrolysis and phosphorylation reactions, from chemical
      energy into mechanical energy. Upon hydrolysis of ATP, say bound to a protein,
      the electrostatic energy of Coulombic repulsion of the ions adenosine diphosphate
      and phosphate is available to assert a force on a neighboring molecular group in
      the protein and can do work on that group, or as the ions recede from each
      without asserting such a force, they gain relative kinetic energy, which, in the
      absence of dissipative collisions that turn this kinetic energy into heat, can be
      converted into any other form of energy and work by an impulse, a collision with
      a neighboring group, without restrictions. Either possibility can be used as a
      source of activation energy for reactions, as a source of energy to surmount
      energy barriers in conformational changes, and as a source of work to be done, as
      in muscle. In some systems where the Gibbs free energy change is fully utilized,
      all of this energy is turned into mechanical energy, and we suggest a similar
      mechanism. From the literature we cite some experimental evidence and several
      quotations indicative of the possibility of our suggestion.

PMID- 16571011
TI  - Conformational analysis of XA and AX dipeptides in water by electronic circular
      dichroism and 1H NMR spectroscopy.
AB  - We measured the temperature-dependent electronic circular dichroism (ECD) spectra
      of AX, XA, and XG dipeptides in D2O. The spectra of all XA and AX peptides
      indicate a substantial population of the polyproline II (PPII) conformation,
      while the ECD spectra of LG, KG, PG, and AG were found to be quantitatively
      different from the alanine-based dipeptides. Additional UV absorption data
      indicate that the ECD spectra of the XG peptides stem from electronic coupling
      between the peptide and the C-terminal group, and that spectral differences
      reflect different orientations of the latter. We also measured the 1H NMR spectra
      of the investigated dipeptides to determine the 3JHalphaNH coupling constants for
      the C-terminal residue. The observed temperature dependence of the ECD spectra
      and the respective room-temperature 3JHalphaNH coupling constants were analyzed
      by a two-state model encompassing PPII and a beta-like conformation. The PPII
      propensity of alanine in the XA series is only slightly modulated by the N
      terminal side chain, and is larger than 50%. As compared to AA, XA peptides
      containing L, P, S, K V, E, T, and I all cause a relative stabilization of the
      extended beta-strand conformation. The PPII fractions of XA peptides varied
      between 0.64 for AA and 0.58 for DA, whereas the PPII fractions of AX peptides
      were much lower. From the investigated AX peptides, only AL and AQ showed the
      expected PPII propensity. We found that AT, AI, and AV clearly prefer an extended
      beta-strand conformation. A quantitative comparison of AA, AAA, and AAAA revealed
      a hierarchy AAAA > AAA approximately AA for the PPII population, in agreement
      with predictions from MD calculations and results from Raman optical activity
      studies (McColl et al. J. Am. Chem. Soc. 2004, 126, 5076).

PMID- 16571013
TI  - Host-guest complexes of carotenoids with beta-glycyrrhizic acid.
AB  - The structure, stability, and reactivity of the host-guest complexes between a
      set of carotenoids and the triterpene glycoside, beta-glycyrrhizic acid (GA),
      were investigated by different physicochemical techniques: high-performance
      liquid chromatography, optical absorption, and fluorescence spectroscopy. It has
      been demonstrated recently that the molecular complexes of GA with a number of
      drugs are characterized by reduced toxicity and increased therapeutic activity of
      these drugs. In the present work it was found that carotenoids form 1:2 complexes
      with GA in aqueous solutions as well as in polar organic solvents, methanol,
      acetonitrile, and dimethylsulfoxide. We assume that the structure of the complex
      is a cycliclike dimer of GA encapsulating a carotenoid molecule. The stability
      constants in all solvents are near 10(4) M(-1). In addition, GA forms inclusion
      complexes with carotenoid radical cations, which results in their stabilization.
      Complex formation (a) decreases the rate of electron transfer from carotenoids to
      electron acceptors (Fe3+ or quinone) and (b) considerably increases the lifetime
      of the carotenoid-quinone charge-transfer complex and the yield of the major
      product (a carotenoid-quinone adduct). A thermodynamic study shows that
      hydrophobic interactions are the main driving force of the carotenoid-GA complex
      formation. These results are important for understanding both the nature of GA
      complexes and the influence of GA on the therapeutic activity of some drugs.
      Furthermore, carotenoid-GA complexes could be used for the design of artificial
      light-harvesting, photoredox, and catalytic systems.

PMID- 16571014
TI  - Ion current calculations based on three dimensional Poisson-Nernst-Planck theory
      for a cyclic peptide nanotube.
AB  - Ion current calculations based on Poisson-Nernst-Planck (PNP) theory are
      performed for a synthetic cyclic peptide nanotube that consists of eight or ten
      cyclo[(-L-Trp-D-Leu-)4] embedded in a lipid bilayer membrane to investigate the
      ion transport properties of the nanotube. To explore systems with arbitrary
      geometries, three-dimensional PNP theory is implemented using a finite difference
      method. The influence of dipolar lipid molecules on the ion currents is also
      examined by turning on or off the charges of the lipid dipoles in
      dipalmitoylphosphatidylcholine (DPPC). Comparisons between the calculated and
      experimentally measured ion currents show that the PNP approach agrees well with
      the measurements at low ion concentrations but overestimates the currents at
      higher concentrations. Concentration profiles reveal the selectivity of the
      peptide nanotube to cations, which is attributed to the negatively charged
      carbonyl oxygens inside the nanotube. The dominant cation and the minimum anion
      concentrations inside the cyclic peptide nanotube suggest that these cyclic
      peptide nanotubes can be employed as ion sensors. In the case of the polar DPPC
      bilayer, smaller currents are obtained in the calculation. The variation of
      current with polarity of the lipids implies that both polar and nonpolar lipid
      bilayer membranes can be utilized to regulate ion currents in the peptide
      nanotube and other ion channels. Strengths and limitations of the PNP theory are
      also discussed.

PMID- 16571015
TI  - Dependence of tryptophan emission wavelength on conformation in cyclic
      hexapeptides.
AB  - The wavelength of maximum emission of tryptophan depends on the local
      electrostatic environment of the indole chromophore. The time-resolved emission
      spectra of seven rigid cyclic hexapeptides containing a single tryptophan residue
      were measured. The emission maxima of the three decay-associated spectra for the
      seven peptides ranged from 341 to 359 nm, suggesting that different tryptophan
      rotamers have different emission maxima even in the case of solvent-exposed
      tryptophans. This conclusion is supported by quantum mechanical/molecular
      dynamics simulations of the six canonical side chain rotamers of tryptophan in
      solvated hexapeptides. The calculated range of emission maxima for the tryptophan
      rotamers of the seven peptides is 344-365 nm. The precision of the wavelength
      calculations and the peptide, water, and charged side chain contributions to the
      spectral shifts are examined. The results indicate that the emission maxima of
      decay-associated spectra can aid in the assignment of fluorescence lifetimes to
      tryptophan rotamers.

PMID- 16571017
TI  - Binding of 8-anilinonaphthalene sulfonate to dimeric and tetrameric concanavalin
      A: energetics and its implications on saccharide binding studied by isothermal
      titration calorimetry and spectroscopy.
AB  - The binding of 8-anilinonaphthalene sulfonate to concanavalin A has been
      investigated. Isothermal titration calorimetry (ITC) and circular dichroism
      studies have been performed under different experimental conditions to understand
      the binding quantitatively and evaluate contributions of different forces
      responsible for it. Isothermal titration calorimetric results of concanavalin A
      with ANS at pH 5.2 and 2.5, where it exists as a dimer, indicated binding
      heterogeneity and two classes of noninteracting sites. Enhancement of the binding
      constants from native to pH 2.5 suggests that the ANS binding is strongly
      influenced by the protein charge and the favorable alteration in the structure of
      concanavalin A as suggested by near-UV CD results. No binding was observed with
      the tetrameric form of concanavalin A, indicating shielding of sites due to
      dimerization of canonical dimers. The results have also demonstrated existence of
      a hydrophobic binding site that is distinct from the saccharide binding site.

PMID- 16571016
TI  - Evidence for many resolvable structures within conformation types of
      electrosprayed ubiquitin ions.
AB  - A new two-dimensional ion mobility spectrometry approach combined with mass
      spectrometry has been used to examine ubiquitin ions in the gas phase. In this
      approach ions are separated in an initial drift tube into conformation types
      (defined by their collision cross sections) and then a gate is used to introduce
      a narrow distribution of mobility-separated ions into a second drift tube for
      subsequent separation. The results show that upon selection a narrow peak shape
      is retained through the second drift tube. This requires that at 300 K the
      selected distribution does not interconvert substantially within the broader
      range of structures associated with the conformation type within the
      approximately 10-20 ms time scale of these experiments. For the [M + 7H]7+ ion,
      it appears that many ( approximately 5-10) narrow selections can be made across
      each of the compact, partially-folded, and elongated conformer types, defined
      previously (Int. J. Mass Spectrom. 1999, 187, 37-47).

PMID- 16571018
TI  - Catalytic mechanism of 6-phosphogluconate dehydrogenase: a theoretical
      investigation.
AB  - Density functional calculations are employed to theoretically explore the
      mechanism of all elementary reaction steps involved in the catalytic reaction of
      6-phosphogluconate dehydrogenase (6PGDH). The model systems we choose for the
      enzyme contain the essential parts of the cofactor (NADP+), the substrate 6
      phosphogluconate (6PG), and some key residues (Lys183 and Glu190) in the active
      site of sheep liver 6PGDH. The effect of the apoenzyme electrostatic environment
      on the studied reaction is treated by the self-consistent reaction-field method.
      Our calculations demonstrate that the first step of the catalytic reaction is the
      formation of a 3-keto 6PG intermediate, which proceeds through a concerted
      transition state involving a hydride transfer from 6PG to NADP+, and a proton
      transfer from 6PG to Lys183. The second step is the elimination of a CO2 molecule
      from 6-PG, concomitant with a proton transfer from Lys183 to 6-PG. In the final
      step, a concerted double proton transfer (one from Glu190 to the substrate,
      another from the substrate to Lys183) results in the final product, the keto form
      of ribulose 5-phosphate (Ru5P). The rate-limiting step is the formation of a 3
      keto 6PG intermediate, with a free energy barrier of 22.7 kcal/mol at room
      temperature in the protein environment, and all three steps are calculated to be
      thermodynamically favorable. These results are in good agreement with the general
      acid/general base mechanism suggested from previous experiments for the 6PGDH
      reaction.

PMID- 16571019
TI  - Specific ion effects at protein surfaces: a molecular dynamics study of bovine
      pancreatic trypsin inhibitor and horseradish peroxidase in selected salt
      solutions.
AB  - The distribution of sodium, choline, sulfate, and chloride ions around two
      proteins, horseradish peroxidase (HRP) and bovine pancreatic trypsin inhibitor
      (BPTI), is investigated by means of molecular dynamics simulations with the aim
      to elucidate ion adsorption at the protein surface. Although the two proteins
      under investigation are very different from each other, the ion distributions
      around them are remarkably similar. Sulfate is always strongly attached to the
      proteins, choline shows a significant, but unspecific, propensity for the protein
      surfaces, and sodium ions have a weak surface affinity, while chloride has
      virtually no preference for the protein surface. In mixtures of all four ion
      species in protein solutions, the resulting distributions are almost a
      superposition of the distributions of sodium sulfate and choline chloride, except
      that sodium partially replaces choline close to the proteins. The present
      simulations support a picture of ions interacting with individual ionic and polar
      amino acid groups rather than with an averaged protein surface. The results thus
      show how subtle the so-called Hofmeister and electroselectivity effects are in
      salt solution of proteins, making all simplified interaction models questionable.

PMID- 16571020
TI  - Bioactive permethrin/beta-cyclodextrin inclusion complex.
AB  - Permethrin is popularly used in a variety of therapeutic areas. However, the poor
      water solubility of permethrin seriously limits its wider clinical applications.
      The present study demonstrates that solubility of permethrin in aqueous solution
      can considerably increase in the presence of beta-cyclodextrin (beta-CD).
      Extensive experimental data along with computational modeling reveal the
      formation of stable permethrin/beta-CD inclusion complexes, including
      permethrin(beta-CD) and permethrin(beta-CD)2, through hydrophobic binding. Both
      permethrin(beta-CD) and permethrin(beta-CD)2 complexes coexisted in aqueous
      solution, and the ratio of the concentration of permethrin(beta-CD) complex to
      that of permethrin(beta-CD)2 complex was dependent on the concentration of beta
      CD. The complexation of permethrin with beta-CD significantly improved the
      bioavailability of permethrin and, therefore, increased the bioactivity. The
      significant increase of the bioactivity of permethrin in the presence of beta-CD
      provides an effective approach to improve the practical use of permethrin in
      public health and agriculture.

PMID- 16571021
TI  - Theoretical studies of [FeFe]-hydrogenase: structure and infrared spectra of
      synthetic models.
AB  - First-principles density functional theory calculations of synthetic models of
      [FeFe]-hydrogenase are used to show that the theoretical methods reproduce
      observed structures and infrared spectra to high accuracy. The accuracy is
      demonstrated for synthetic Fe(I)Fe(I) models ([(mu-PDT)Fe2(CO)6] and
      [(CN)(CO)2(mu-PDT)Fe2(CO)2(CN)]2-), for which we show that their infrared spectra
      are sensitive to the geometric arrangement of their CO/CN ligands and can be used
      in conjunction with quantum-mechanical total energies to predict the correct
      ligand geometry. We then analyze and predict the structure of mixed-valence
      Fe(II)Fe(I) models ([(mu-MeSCH2C(Me)(CH2S)2)Fe2(CO)4(CN)2]x-). These capabilities
      promise to distinguish among the various structural isomers of the enzyme's
      active site which are consistent with the limited accuracy of the X-ray
      observations.

PMID- 16571022
TI  - Alpha-synuclein structures probed by 5-fluorotryptophan fluorescence and 19F NMR
      spectroscopy.
AB  - Alpha-synuclein, the main protein component of fibrillar deposits found in
      Parkinson's disease, is intrinsically disordered in vitro. Site-specific
      information on the protein conformation has been obtained by biosynthetic
      incorporation of an unnatural amino acid, 5-fluorotryptophan (5FW), into the
      recombinant protein. Using fluorescence and 19F NMR spectroscopy, we have
      characterized three proteins with 5FW at positions 4, 39, and 94. Steady-state
      emission spectra (maxima at 353 nm; quantum yields approximately 0.2) indicate
      that all three indole side chains are exposed to the aqueous medium. Virtually
      identical single-exponential excited-state decays (tau approximately 3.4 ns) were
      observed in all three cases. Single 19F NMR resonances were measured for W4, W39,
      and W94 at -49.0 +/- 0.1 ppm. Our analysis of the spectroscopic data suggests
      that the protein conformations are very similar in the regions near the three
      sites.

PMID- 16571023
TI  - Modified lithium borohydrides for reversible hydrogen storage.
AB  - In an attempt to develop lithium borohydrides as reversible hydrogen storage
      materials with high hydrogen storage capacities, the feasibility of reducing the
      dehydrogenation temperature of the lithium borohydride and moderating
      rehydrogenation conditions was explored. The lithium borohydride was modified by
      ball milling with metal oxides and metal chlorides as additives. The modified
      lithium borohydrides released 9 wt % hydrogen starting from 473 K. The dehydrided
      modified lithium borohydrides absorbed 7-9 wt % hydrogen at 873 K and 7 MPa. The
      modification with additives reduced the dehydriding starting temperature from 673
      to 473 K and moderated the rehydrogenation conditions from 923 K/15 MPa to 873
      K/7 MPa. XRD and SEM analysis revealed the formation of an intermediate compound
      that might play a key role in changing the reaction path, resulting in the lower
      dehydriding temperature and reversibility. The reversible hydrogen storage
      capacity of the oxide-modified lithium borohydrides decreased gradually during
      hydriding/dehydriding cycling. One of the possible reasons for this effect might
      be the loss of boron during dehydrogenation, but this can be prevented by
      changing the dehydriding path using appropriate additives. The additives reduced
      the dehydriding temperature and improved the reversibility, but they also reduced
      the hydrogen storage capacity. The best compromise can be reached by selecting
      appropriate additives, optimizing the additive loading, and using new synthesis
      processes other than ball milling.

PMID- 16571024
TI  - Stochastic model of photodynamics in multichromophoric conjugated polymers.
AB  - A stochastic model of triplet exciton dynamics in multichromophoric conjugated
      polymers is presented and analyzed in detail, with a focus on the single molecule
      spectroscopy observables. The model deals with the evolution of a discrete
      statistical distribution of triplets in isolated polymer molecules. This approach
      should provide more accurate quantitative information on the dynamic processes
      involved, as compared to the previously used two-state model which assumes that a
      conjugated polymer cannot contain more than one triplet. In particular, it allows
      for determination of the triplet-triplet annihilation rate.

PMID- 16571025
TI  - Solvatochromic parameters for binary mixtures of 1-(1-butyl)-3-methylimidazolium
      tetrafluoroborate with some protic molecular solvents.
AB  - The solvatochromic parameters (ET(N), normalized polarity parameter; pi*,
      dipolarity/polarizability; beta, hydrogen-bond acceptor basicity; alpha, hydrogen
      bond donor acidity) were determined for binary solvent mixtures of 1-(1-butyl)-3
      methylimidazolium tetrafluoroborate ([bmim]BF4) with water, methanol, and ethanol
      at 25 degrees C over the whole range of mole fractions. In nonaqueous solutions,
      the value of the mixture increases with mole the fraction of [bmim]BF4 and then
      decreases gradually to the value of pure [bmim]BF4. Positive deviation from ideal
      behavior was observed for the solvent parameters ET(N), pi*, and alpha, whereas
      the deviation of the beta parameter is negative. The applicability of the
      combined nearly ideal binary solvent/Redlich-Kister equation for the correlation
      of various solvatochromic parameters with solvent composition was proved too for
      the first time. This equation provides a simple computational model to correlate
      and/or predict various solvatochromic parameters for many binary solvent systems.
      The correlation between the calculated and the experimental values of various
      parameters was in accordance with this model. Solute-solvent and solvent-solvent
      interactions have been applied for interpretation of the results.

PMID- 16571026
TI  - Comment on "photoelectron spectroscopic investigation of nitrogen-doped titania
      nanoparticles".

PMID- 16571030
TI  - Charge resonance character in the charge transfer state of bianthryls: effect of
      symmetry breaking on time-resolved near-IR absorption spectra.
AB  - We study the effects of symmetry breaking on the photogenerated intramolecular
      charge transfer (CT) state of 9,9'-bianthryl (BA) with femtosecond time-resolved
      near-IR spectroscopy. The time-resolved near-IR spectra are measured in
      acetonitrile for a symmetric substituted derivative of 10,10'-dicyano-9,9'
      bianthryl (DCBA) and asymmetric substituted derivatives of 10-cyano-9,9'
      bianthryl (CBA) and 9-(N-carbazolyl)anthracene (C9A), as well as nonsubstituted
      BA. The transient near-IR absorption spectrum of each compound at 0 ps has a
      locally excited (LE) absorption band, which agrees with the transient absorption
      band of the corresponding monomer unit. At 3 ps after the photoexcitation, the
      symmetric compounds show a broad charge transfer (CT) absorption band, whereas no
      absorption peak appears in the spectra of the asymmetric compounds. The broad CT
      absorption at 1250 nm only observed for the symmetric compounds can be attributed
      to the charge resonance transition associated with two equivalent charge
      separated states.

PMID- 16571029
TI  - Mindless chemistry.
AB  - Applications of an automated stochastic search procedure for locating all
      possible minima with a given composition are illustrated by the pentatomic
      molecules BCNOS, CAlSiPS, C(4)B(-), C(4)Al(-), and CBe(4)(2-), as well as by
      C(6)Be, the C(6)Be(2-) dianion, and C(6)H(2). All previously identified minima
      were reproduced, and many new structures, often with nonintuitive geometries,
      were found.

PMID- 16571031
TI  - Early stages of styrene-isoprene copolymerization in gas phase clusters probed by
      resonance enhanced multiphoton ionization.
AB  - We present direct evidence for the formation of the covalent bonded styrene
      (isoprene)(2) oligomer and the isoprene dimer ions following resonance ionization
      of the gas phase styrene-isoprene binary clusters. The application of resonance
      ionization to study polymerization reactions in clusters provides new information
      on the structure and mechanism of formation of the early stages of polymerization
      and holds considerable promise for the discovery of new initiation mechanisms and
      for the development of novel materials with unique properties.

PMID- 16571032
TI  - Uncovering the fundamental chemistry of alkyl + O2 reactions via measurements of
      product formation.
AB  - The reactions of alkyl radicals (R) with molecular oxygen (O(2)) are critical
      components in chemical models of tropospheric chemistry, hydrocarbon flames, and
      autoignition phenomena. The fundamental kinetics of the R + O(2) reactions is
      governed by a rich interplay of elementary physical chemistry processes. At low
      temperatures and moderate pressures, the reactions form stabilized alkylperoxy
      radicals (RO(2)), which are key chain carriers in the atmospheric oxidation of
      hydrocarbons. At higher temperatures, thermal dissociation of the alkylperoxy
      radicals becomes more rapid and the formation of hydroperoxyl radicals (HO(2))
      and the conjugate alkenes begins to dominate the reaction. Internal isomerization
      of the RO(2) radicals to produce hydroperoxyalkyl radicals, often denoted by
      QOOH, leads to the production of OH and cyclic ether products. More crucially for
      combustion chemistry, reactions of the ephemeral QOOH species are also thought to
      be the key to chain branching in autoignition chemistry. Over the past decade,
      the understanding of these important reactions has changed greatly. A
      recognition, arising from classical kinetics experiments but firmly established
      by recent high-level theoretical studies, that HO(2) elimination occurs directly
      from an alkylperoxy radical without intervening isomerization has helped resolve
      tenacious controversies regarding HO(2) formation in these reactions. Second, the
      importance of including formally direct chemical activation pathways, especially
      for the formation of products but also for the formation of the QOOH species, in
      kinetic modeling of R + O(2) chemistry has been demonstrated. In addition, it
      appears that the crucial rate coefficient for the isomerization of RO(2) radicals
      to QOOH may be significantly larger than previously thought. These
      reinterpretations of this class of reactions have been supported by comparison of
      detailed theoretical calculations to new experimental results that monitor the
      formation of products of hydrocarbon radical oxidation following a pulsed
      photolytic initiation. In this article, these recent experiments are discussed
      and their contributions to improving general models of alkyl + O(2) reactions are
      highlighted. Finally, several prospects are discussed for extending the
      experimental investigations to the pivotal questions of QOOH radical chemistry.

PMID- 16571033
TI  - Critical dynamics of the binary system nitroethane/3-methylpentane: relaxation
      rate and scaling function.
AB  - Shear viscosity and dynamic light scattering measurements as well as ultrasonic
      spectrometry studies of the nitroethane/3-methylpentane mixture of critical
      composition have been performed at various temperatures near the critical
      temperature, T(c). A combined evaluation of the shear viscosity and mutual
      diffusion coefficient data yielded the amplitude, xi(0), of the fluctuation
      correlation length, xi, assumed to follow power law, and the relaxation rate,
      Gamma, or order parameter fluctuations. The latter was found to follow power law
      with the theoretical universal exponent. The amplitudes xi(0) = 0.23 +/- 0.02 nm
      and Gamma(0) = (125 +/- 5) x 10(9) s(-1) nicely agree with literature values.
      Using the relaxation rates resulting from the viscosity and diffusion coefficient
      data, the scaling function has been calculated assuming the ultrasonic spectra to
      be composed of a critical part and a noncritical background contribution. The
      experimental scaling function fits well to the predictions of the Bhattacharjee
      Ferrell dynamic scaling model with scaled half-attenuation frequency,
      Omega(BF)1/2= 2.1. The amplitude of the sonic spectra yields the amount |g| =
      0.26 of the adiabatic coupling constant, g, in fair agreement with -0.29 from
      another thermodynamic relation.

PMID- 16571034
TI  - Solvent and linker influences on AQ(*-)/dA(*+) charge-transfer state energetics
      and dynamics in anthraquinonyl-linker-deoxyadenosine conjugates.
AB  - The goal of this work is to produce high yields of long-lived AQ(*-)/dA(*+)
      charge transfer (CT) excited states (or photoproducts). This goal fits within a
      larger context of trying generally to produce high yields of long-lived CT
      excited states within DNA nucleoside conjugates that can be incorporated into DNA
      duplexes. Depending upon the energetics of the anthraquinonyl (AQ) (3)(pi,pi)
      state as well as the reduction potentials of the subunits in particular
      anthraquinonyl-adenine conjugates, CT quenching of the AQ (3)(pi,pi*) state may
      or may not occur in polar organic solvents. In MeOH, bis(3',5'-O-acetyl)-N(6)
      (anthraquinone-2-carbonyl)-2'-deoxyadenosine (AQCOdA) behaves as intended and
      forms a (3)(AQ(*-)/dA(*+)) CT state with a lifetime of 3 ns. However, in nonpolar
      THF the AQ(*-)/dA(*+) CT states of AQCOdA are too high in energy to be formed,
      and in DMSO a (1)(AQ(*-)/dA(*+)) CT state is formed but lives only 6 ps. Although
      the lowest energy excited state for AQCOdA in MeOH is a (3)(AQ(*-)/dA(*+)) CT
      state, for N(6)-(anthraquinone-2-methylenyl)-2'-deoxyadenosine (AQMedA) in the
      same solvent it is a (3)(pi,pi*) state. Changing the linking carbonyl in AQCOdA
      to methylene in AQMedA makes the anthraquinonyl subunit harder to reduce by 166
      mV. This raises the energy of the (3)(AQ(*-)/dA(*+)) CT state above that of the
      (3)(pi,pi*) in AQMedA. The conclusion is that anthraquinonyl-dA conjugates will
      not have lowest energy AQ(*-)/dA(*+) CT states in polar organic solvents unless
      the anthraquinonyl subunit is also substituted with an electron-withdrawing group
      that raises the AQ-subunit's reduction potential above that of AQ. A key finding
      in this work is that the lifetime of the (3)(AQ(*-)/dA(*+)) CT excited state (ca.
      3 ns) is ca. 500-times longer than that of the corresponding (1)(AQ(*-)/dA(*+))
      CT excited state (ca. 6 ps).'

PMID- 16571035
TI  - Photophysical and theoretical investigations of oligo(p-phenyleneethynylene)s:
      effect of alkoxy substitution and alkyne-aryl bond rotations.
AB  - The unique photophysical, conformational, and electronic properties of two model
      phenyleneethynylene-based rigid rod molecular systems, possessing dialkoxy
      substitutions, are reported in comparison with an unsubstituted system. Twisting
      of the phenyl rings along the carbon-carbon triple bond is almost frictionless in
      these systems giving rise to planar as well as several twisted ground-state
      conformations, and this results in broad structureless absorption in the spectral
      region of 250-450 nm. In the case of 1,4-bis(phenylethynyl)benzene, a broad
      absorption band was observed due to the HOMO-LUMO transition, whereas dialkoxy
      substituted compounds possess two well-separated bands. Dialkoxy substitution in
      the 2,5-position of the phenyl ring in phenyleneethynylenes alters its central
      arene pi-orbitals through the resonance interaction with oxygen lone pairs
      resulting in similar orbital features for HOMO and HOMO-1/HOMO-2. Electronic
      transition from the low-lying HOMO-1/HOMO-2 orbital to LUMO results in the high
      energy band, and the red-shifted band originates from the HOMO-LUMO transition.
      The first excited-state transition energies at different dihedral angles,
      calculated by the TDDFT method, indicate that the orthogonal conformation has the
      highest excitation energy with an energy difference of 15 kcal/mol higher than
      the low-lying planar conformation. The emission of these compounds originates
      preferentially from the more relaxed planar conformation resulting in well
      defined vibronic features. The fluorescence spectral profile and lifetimes were
      found to be independent of excitation wavelengths, confirming the existence of a
      single emitting species.

PMID- 16571037
TI  - Absorption spectra, photophysical properties, and redox behavior of ruthenium(II)
      polypyridine complexes containing accessory dipyrromethene-BF2 chromophores.
AB  - The six multichromophoric species 1-6, containing the potentially luminescent
      Ru(II) polypyridine subunits and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
      fluorophores (dipyrromethene-BF(2) dyes, herein after called bodipy), have been
      prepared and their absorption spectra, luminescence properties (both at room
      temperature in fluid solution and at 77 K in rigid matrix), and redox properties
      have been investigated (for the structuralformulas of all the compounds, see
      Figure 1). For comparison purposes, also the same properties of the bodipy-based
      free ligands have been examined. Three of the multichromophoric species (1-3) are
      based on the Ru(bpy)(3)-type metal subunit, whereas 4-6 are based on the
      Ru(terpy)(2)-type metal subunit. Transient absorption spectroscopy at room
      temperature of all the compounds has also been performed. The absorption spectra
      of all the metal complexes show features that can be assigned to the Ru(II)
      polypyridine subunits and to the bodipy centers. In particular, the lowest energy
      spin-allowed pi-pi* transition of the bodipy groups dominates the visible region,
      peaking at about 530 nm. All the new complexes exhibit a rich redox behavior,
      with reversible processes attributed to specific sites, indicating a small
      perturbation of each redox center and therefore highlighting the supramolecular
      nature of the multichromophoric assemblies. Despite the good luminescence
      properties of the separated components, 1-6 do not exhibit any luminescence at
      room temperature; however, transient absorption spectroscopy evidences that for
      all of them a long-lived (microsecond time scale) excited state is formed, which
      is identified as the bodipy-based triplet state. Pump-probe transient absorption
      spectroscopy suggests that such a triplet state is formed from the promptly
      prepared bodipy-based (1)pi-pi* state in most cases by the intervention of a
      charge-separated level. At 77 K, all the complexes except complex 1 exhibit the
      bodipy-based fluorescence, although with a slightly shortened lifetime compared
      to the corresponding free ligand(s), and 4-6 also exhibit a phosphorescence
      assigned to the bodipy subunits. Phosphorescence of bodipy species had never been
      reported in the literature to the best of our knowledge: in the present cases we
      propose that it is an effective decay process thanks to the presence of the
      ruthenium heavy atom and of the closely lying (3)MLCT state of the Ru(terpy)(2)
      type subunits.

PMID- 16571038
TI  - Free-jet rotational spectrum and tunneling motion of difluoromethane...xenon.
AB  - The rotational spectra of three isotopologues of difluoromethane...xenon have
      been investigated by free-jet millimeter-wave absorption spectroscopy. Only mu(c)
      type transitions have been observed, all of them evenly split due to the internal
      motion of Xe relative to the difluoromethane moiety. The vibrational splitting,
      39.1(3) MHz, has been used to estimate the tunneling barrier, V(2) = 109 cm(-1).
      Information on the dissociation energy has been deduced from centrifugal
      distortion effects (E(B) = 1.8 kJ mol(-1)). The xenon atom lies in the sigma(v)
      symmetry plane of difluoromethane containing the hydrogen atoms, at an r(0)
      distance of 3.816 A from its center of mass (cm), and forms a Xe-cm-C r(0) angle
      of 118 degrees . The observed conformation is in agreement with the minimum found
      with a distributed polarizability model.

PMID- 16571036
TI  - Potassium ion controlled switching of intra- to intermolecular electron transfer
      in crown ether appended free-base porphyrin-fullerene donor-acceptor systems.
AB  - Photoinduced electron transfer in intramolecularly interacting free-base
      porphyrin bearing one or four 18-crown-6 ether units at different positions of
      the porphyrin macrocycle periphery and pristine fullerene was investigated in
      polar benzonitrile and nonpolar o-dichlorobenzene and toluene solvents. Owing to
      the presence of two modes of binding, stable dyads were obtained in which the
      binding constants, K, were found to range between 4.2 x 10(3) and 10.4 x 10(3) M(
      1) from fluorescence quenching data depending upon the location and number of
      crown ether entities on the porphyrin macrocycle and the solvent. Computational
      studies using the B3LYP/3-21G() method were employed to arrive at the geometry
      and electronic structure of the intramolecular dyads. The energetics of the redox
      states of the dyads were established from cyclic voltammetric studies. Under the
      intramolecular conditions, both the steady-state and time-resolved emission
      studies revealed efficient quenching of the singlet excited free-base porphyrin
      in these dyads, and the measured rates of charge separation, k(CS), were found to
      be in the 10(8)-10(9) s(-1) range. Nanosecond transient absorption studies were
      performed to characterize the electron-transfer products and to evaluate the
      charge-recombination rates. Shifting of the electron-transfer pathway from the
      intra- to intermolecular route was achieved by complexing potassium ions to the
      crown ether cavity(ies) in benzonitrile. This cation complexation weakened the
      intramolecular interactions between fullerene and the crown ether appended free
      base porphyrin supramolecules, and under these conditions, intermolecular type
      interactions were mainly observed. Reversible inter- to intramolecular electron
      transfer was also accomplished by extracting the potassium ions of the complex
      with the addition of 18-crown-6. The present study nicely demonstrates the
      application of supramolecular methodology to control the excited-state electron
      transfer path in donor-acceptor dyads.

PMID- 16571039
TI  - Electron capture detector response and dissociative electron attachment cross
      sections in chloroalkanes and chloroalkenes.
AB  - Electron capture detectors (ECDs) are widely used in gas chromatography to detect
      electronegative compounds. In this work, we examine the connections between the
      ECD response and the cross sections for dissociative electron attachment (DEA)
      determined from low energy electron beam studies in the chloroalkane family,
      stressing in particular the role of temporary anion state energies. We show that
      attachment rate coefficients computed from these cross sections are well
      correlated with ECD response, and that the latter decreases exponentially with
      increasing energies of the lowest anion states. ECD measurements are also carried
      out in monochloroalkanes substituted with unsaturated ethenyl and phenyl
      moieties, and the response is shown to depend strongly on the mixing between the
      unsaturated pi* and the C-Cl sigma* temporary anions as exhibited by the vertical
      attachment energies (VAEs) of these states. The results show good correlations
      between the chloroalkene and phenyl chloride ECD responses and the VAEs for the
      mixed states.

PMID- 16571040
TI  - Spectroscopic characterization of a series of platinum acetylide complexes having
      a localized triplet exciton.
AB  - In this work, we describe the spectroscopic properties of a series of platinum
      complexes containing one acetylide ligand per platinum, having the chemical
      formula trans-Pt(PBu(3))(2)((C[triple bond]CC(6)H(4))(n)()-H)Cl, n = 1-3
      (designated as half-PEn-Pt) and compare their spectroscopic behavior with the
      well-characterized series trans-Pt(PBu(3))(2)((C[triple bond]CC(6)H(4))(n)-H)(2),
      n = 1-3 (designated as PEn-Pt). This comparison aims to determine if the triplet
      state of PEn-Pt is confined to one ligand or delocalized across the central
      platinum atom. We measured ground-state absorption spectra, fluorescence spectra,
      phosphorescence spectra, and triplet-state absorption spectra. The ground-state
      absorption spectra and fluorescence spectra both showed a blue shift when
      comparing half-PEn-Pt with PEn-Pt, showing the S(1) state is delocalized across
      the platinum. In contrast, the phosphorescence spectra of the two types of
      compounds had the same 0-0 band energy, showing the T(1) state was confined to
      one ligand in PEn-Pt. The triplet state absorption spectra blue shifted when
      comparing half-PEn-Pt with PEn-Pt, showing the T(n) state was delocalized across
      the central platinum. This comparison supports recently published work that
      suggested this confinement effect (Rogers, J. E et al. J. Chem. Phys. 2005, 122,
      214701).

PMID- 16571041
TI  - Identification of C5Hx isomers in fuel-rich flames by photoionization mass
      spectrometry and electronic structure calculations.
AB  - The isomeric composition of C(5)H(x) (x = 2-6, 8) flame species is analyzed for
      rich flames fueled by allene, propyne, cyclopentene, or benzene. Different
      isomers are identified by their known ionization energies and/or by comparison of
      the observed photoionization efficiencies with theoretical simulations based on
      calculated ionization energies and Franck-Condon factors. The experiments combine
      flame-sampling molecular-beam mass spectrometry with photoionization by tunable
      vacuum-UV synchrotron radiation. The theoretical simulations employ the
      rovibrational properties obtained with B3LYP/6-311++G(d,p) density functional
      theory and electronic energies obtained from QCISD(T) electronic structure
      calculations extrapolated to the complete basis set limit. For C(5)H(3), the
      comparison reveals the presence of both the H(2)CCCCCH (i-C(5)H(3)) and the
      HCCCHCCH (n-C(5)H(3)) isomer. The simulations also suggest a modest amount of
      cyclo-CCHCHCCH-, which is consistent with a minor signal for C(5)H(2) that is
      apparently due to cyclo-CCHCCCH-. For C(5)H(4), contributions from the
      CH(2)CCCCH(2) (1,2,3,4-pentatetraene), CH(2)CCHCCH, and CH(3)CCCCH (1,3
      pentadiyne) isomers are evident, as is some contribution from CHCCH(2)CCH (1,4
      pentadiyne) in the cyclopentene and benzene flames. Signal at m/z = 65 originates
      mainly from the cyclopentadienyl radical. For C(5)H(6), contributions from
      cyclopentadiene, CH(3)CCCHCH(2), CH(3)CHCHCCH, and CH(2)CHCH(2)CCH are observed.
      No signal is observed for C(5)H(7) species. Cyclopentene, CH(2)CHCHCHCH(3) (1,3
      pentadiene), CH(3)CCCH(2)CH(3) (2-pentyne), and CH(2)CHCH(2)CHCH(2) (1,4
      pentadiene) contribute to the signal at m/z = 68. Newly derived ionization
      energies for i- and n-C(5)H(3) (8.20 +/- 0.05 and 8.31 +/- 0.05 eV,
      respectively), CH(2)CCHCCH (9.22 +/- 0.05 eV), and CH(2)CHCH(2)CCH (9.95 +/- 0.05
      eV) are within the error bars of the QCISD(T) calculations. The combustion
      chemistry of the observed C(5)H(x) intermediates and the impact on flame
      chemistry models are discussed.

PMID- 16571042
TI  - Photoreactions in the gas-phase complexes of Mg(*+)-dioxanes.
AB  - Photoreactions in the gas-phase complexes Mg(*+)(1,4-dioxane) (1) and Mg(*+)(1,3
      dioxane) (1M) have been examined in the wavelength region of 230-440 nm.
      Photoproduct assignments are facilitated with the help of deuterium substitution
      experiments. The main energy relaxation channel for both photoexcited complexes
      is the evaporation of Mg(*+). Also observed from 1 are rich photoproducts with
      m/z 28, 41, 54-58, 67, 69, and 88; the most abundant one at m/z 54 is designated
      to Mg(*+)(O=CH(2)). In marked contrast, the photolysis of 1M yields only
      Mg(*+)(O=CH(2)) other than Mg(*+). Density functional calculations are performed
      to obtain optimized geometries and potential energy surfaces of 1 and 1M.
      Although Mg(*+)(chair-1,4-C(4)H(8)O(2)) (1a) and Mg(*+)(boat-1,4-C(4)H(8)O(2))
      (1b) are comparable in energy, the much better agreement of the experimental
      action spectrum of Mg(*+)(1,4-C(4)H(8)O(2)) with the calculated absorption
      spectrum of 1a than with that of 1b indicates the predominance of 1a in the
      source due to the stability of the chair-1,4-dioxane. For photoreactions, the C-O
      bond is found to be much more prone to rupture than the C-C bond due to the
      coordination of O to Mg(+) in the parent complexes. Photoreaction mechanisms are
      discussed in terms of two key insertion complexes, which rationalize all of the
      observed photoproducts.

PMID- 16571043
TI  - Magnitude of the CH/pi interaction in the gas phase: experimental and theoretical
      determination of the accurate interaction energy in benzene-methane.
AB  - The accurate CH/pi interaction energy of the benzene-methane model system was
      experimentally and theoretically determined. In the experiment, mass analyzed
      threshold ionization spectroscopy was applied to the benzene-methane cluster in
      the gas phase, prepared in a supersonic molecular beam. The binding energy in the
      neutral ground state of the cluster, which is regarded as the CH/pi interaction
      energy for this model system, was evaluated from the dissociation threshold
      measurements of the cluster cation. The experimentally determined binding energy
      (D(0)) was 1.03-1.13 kcal/mol. The interaction energy of the model system was
      calculated by ab initio molecular orbital methods. The estimated CCSD(T)
      interaction energy at the basis set limit (D(e)) was -1.43 kcal/mol. The
      calculated binding energy (D(0)) after the vibrational zero-point energy
      correction (1.13 kcal/mol) agrees well with the experimental value. The effects
      of basis set and electron correlation correction procedure on the calculated
      CH/pi interaction energy were evaluated. Accuracy of the calculated interaction
      energies by DFT methods using BLYP, B3LYP, PW91 and PBE functionals was also
      discussed.

PMID- 16571044
TI  - Time-dependent infrared emission following photodissociation of nitromethane and
      chloropicrin.
AB  - Nitromethane (CH(3)NO(2)) and its chlorinated analogue, chloropicrin
      (CCl(3)NO(2)), were photolyzed at 193, 248, and 266 nm, and the products were
      observed by time-dependent Fourier transform infrared emission spectroscopy. At
      193 and 248 nm, the primary photodissociation pathway for nitromethane was
      cleavage of the C-N bond to produce CH(3) + NO(2)(A (2)B(2)). At 266 nm, weak
      emission was observed following photodissociation of nitromethane, but an
      infrared spectrum could not be obtained. The photodissociation of chloropicrin at
      193 nm produced the analogous product channel CCl(3) + NO(2)(A (2)B(2)) in
      addition to several other product channels. At 248 and 266 nm, only CCl(3) +
      NO(2)(A (2)B(2)) was observed. The production of phosgene (CCl(2)O) from
      chloropicrin photodissociation was not observed in this study.

PMID- 16571045
TI  - Theory and application of dissociative electron capture in molecular
      identification.
AB  - The coupling of an electron monochromator (EM) to a mass spectrometer (MS) has
      created a new analytical technique, EM-MS, for the investigation of electrophilic
      compounds. This method provides a powerful tool for molecular identification of
      compounds contained in complex matrices, such as environmental samples. In
      particular, EM-MS has been applied to the detection of nitrated aromatic
      compounds, many of which are potent mutagens and/or carcinogens and are
      considered environmental hazards. EM-MS expands the application and selectivity
      of traditional MS through the inclusion of a new dimension in the space of
      molecular characteristics-the electron resonance energy spectrum. EM-MS also
      enhances detection sensitivity as well because the entire electron flux of the
      proper energy can be delivered into the negative ion resonance that is
      analytically most useful to solving the problem at hand. However, before this
      tool can realize its full potential, it will be necessary to create a library of
      resonance energy scans from standards of the molecules for which EM-MS offers a
      practical means of detection. Unfortunately, the number of such standards is very
      large and not all of the compounds are commercially available, making this
      library difficult to construct. Here, an approach supplementing direct
      measurement with chemical inference and quantum scattering theory is presented to
      demonstrate the feasibility of directly calculating resonance energy spectra.
      This approach makes use of the symmetry of the transition-matrix element of the
      captured electron to discriminate between the spectra of isomers. As a way of
      validating this approach, the resonance values for 25 nitrated aromatic compounds
      were measured along with their relative abundance. Subsequently, the spectra for
      the isomers of nitrotoluene were shown to be consistent with the symmetry-based
      model. The initial success of this treatment suggests that it might be possible
      to predict negative ion resonances and thus create a library of EM-MS standards.

PMID- 16571046
TI  - Atmospheric oxidation pathways of acetic acid.
AB  - One of the most abundant carboxylic acids measured in the atmosphere is acetic
      acid (CH(3)C(O)OH), present in rural, urban, and remote marine environments in
      the low-ppb range. Acetic acid concentrations are not well reproduced in global 3
      D atmospheric models because of the poor inventory of sources and sinks to model
      its global distribution. To understand the complete oxidation of acetic acid in
      the atmosphere initiated by OH radicals, ab initio calculations are performed to
      describe in detail the energetics of the reaction potential energy surface (PES).
      The proposed reaction mechanism suggests that the CH(3)C(O)OH + OH reaction takes
      place via three pathways: the addition of OH to the central carbon, the
      abstraction of a methyl hydrogen, and the abstraction of an acidic hydrogen. The
      PES is characterized by prereactive H-complexes, transition states, and more
      interestingly unique radical-mediated isomerization reactions. From the analysis
      of the energetics, acetic acid atmospheric oxidation will proceed mainly via the
      abstraction of the acidic hydrogen, consistent with previous experimental and
      theoretical studies. The major byproducts from each pathway are identified.
      Glyoxylic acid is suggested to be a major byproduct of the atmospheric oxidation
      of acetic acid. The atmospheric fate of glyoxylic acid is discussed.

PMID- 16571047
TI  - Theoretical studies of the photochemical dynamics of acetylacetone: isomerzation,
      dissociation, and dehydration reactions.
AB  - The potential energy surfaces of the C-O cleavage, rotational isomerization, keto
      enolic tautomerization, and dehydration reactions of acetylacetone in the lowest
      triplet and ground states have been determined using the complete active space
      self-consistent field and density functional theory methods. The main
      photochemical mechanism obtained indicates that the acetylacetone molecule in the
      S(2)((1)pipi*) state can relax to the T(1)((3)pipi*) state via the S(2)-S(1)
      vibronic interaction and an S(1)/T(1)/T(2) intersection. The C-O fission pathway
      is the predominant dissociation process in the T(1)((3)pipi) state. Rotational
      isomerization reactions proceed difficultly in the ground state but very easily
      in the T(1)((3)pipi*) state. Keto-enolic tautomerization takes place with little
      probability for acetylacetone in the gas phase.

PMID- 16571048
TI  - Falloff curves for the Reaction CH3 + O2 (+ M) --> CH3O2 (+ M) in the pressure
      range 2-1000 bar and the temperature range 300-700 K.
AB  - The reaction CH(3) + O(2) (+M) --> CH(3)O(2) (+M) was studied in the bath gases
      Ar and N(2) in a high-temperature/high-pressure flow cell at pressures ranging
      from 2 to 1000 bar and at temperatures between 300 and 700 K. Methyl radicals
      were generated by laser flash photolysis of azomethane or acetone. Methylperoxy
      radicals were monitored by UV absorption at 240 nm. The falloff curves of the
      rate constants are represented by the simplified expression k/k(infinity)
      approximately [x/(1 + x)]F(cent)(1/{1+[(log)(x)/)(N)(]2}) with x =
      k(0)/k(infinity) F(cent) approximately 0.33, and N approximately 1.47, where k(0)
      and k(infinity) denote the limiting low and high-pressure rate constants,
      respectively. At low temperatures, 300-400 K, and pressures >300 bar, a fairly
      abrupt increase of the rate constants beyond the values given by the falloff
      expressions was observed. This effect is attributed to a contribution from the
      radical complex mechanism as was also observed in other recombination reactions
      of larger radicals. Equal limiting low-pressure rate constants k(0) = [M]7 x 10(
      31)(T/300 K)(-3.0) cm(6) molecule(-2) s(-1) were fitted for M = Ar and N(2)
      whereas limiting high-pressure rate constants k(infinity) = 2.2 x 10(-12)(T/300
      K)(0.9) cm(3) molecule(-1) s(-1) were approached. These values are discussed in
      terms of unimolecular rate theory. It is concluded that a theoretical
      interpretation of the derived rate constants has to be postponed until better
      information of the potential energy surface is available. Preliminary theoretical
      evaluation suggests that there is an "anisotropy bottleneck" in the otherwise
      barrierless interaction potential between CH(3) and O(2).

PMID- 16571050
TI  - Kinetics of the OH + HCNO reaction.
AB  - The kinetics of the OH + HCNO reaction was studied. The total rate constant was
      measured by LIF detection of OH using two different OH precursors, both of which
      gave identical results. We obtain k = (2.69 +/- 0.41) x 10(-12) exp[(750.2 +/-
      49.8)/T] cm(3) molecule(-1) s(-1) over the temperature range 298-386 K, with a
      value of k = (3.39 +/- 0.3) x 10(-11) cm(3) molecule(-1) s(-1) at 296 K. CO,
      H(2)CO, NO, and HNO products were detected using infrared laser absorption
      spectroscopy. On the basis of these measurements, we conclude that CO + H(2)NO
      and HNO + HCO are the major product channels, with a minor contribution from
      H(2)CO + NO.

PMID- 16571049
TI  - Reaction of Cl atoms with C6F13CH2OH, C6F13CHO, and C3F7CHO.
AB  - The Cl atom initiated oxidation of C(6)F(13)CH(2)OH, C(6)F(13)CHO, and
      C(3)F(7)CHO was investigated at 298 K and 1000 mbar pressure of air in a
      photoreactor using in situ Fourier transform infrared (FTIR) analysis. The rate
      coefficient for the reaction Cl + C(6)F(13)CH(2)OH (reaction 2) was measured
      using a relative method: k(2) = (6.5 +/- 0.8) x 10(-13) cm(3) molecule(-1) s(-1).
      C(6)F(13)CHO was detected as the major primary product, while CO and CF(2)O were
      found to be the major secondary products. A fitting procedure applied to the
      concentration-time profiles of C(6)F(13)CHO provided a production yield of (1.0
      +/- 0.2) for this aldehyde in reaction 2, and the rate coefficient for the
      reaction Cl + C(6)F(13)CHO (reaction 4) was k(4) = (2.8 +/- 0.7) x 10(-12) cm(3)
      molecule(-1) s(-1). A high CO yield observed in the oxidation of
      C(6)F(13)CH(2)OH, (52 +/- 1)%, is attributed to the Cl atom initiated oxidation
      of C(6)F(13)CHO. High CO yields, (61 +/- 2)% and (85 +/- 5)%, were also measured
      in the Cl atom initiated oxidation of C(3)F(7)CHO in air and nitrogen,
      respectively. These high CO yields suggest the occurrence of a decomposition
      reaction of the perfluoroacyl, C(6)F(13)CO, and C(3)F(7)CO radicals to form CO
      which will compete with the combination reaction of these radicals with oxygen to
      form perfluoroacyl peroxy radicals in the presence of air. The latter radicals
      C(n)F(2)(n)(+1)CO(O)(2) (n = 6-12), through their reaction with HO(2) radicals,
      are currently considered as a possible source of persistent perfluorocarboxylic
      acids which have been detected in the environment. The consequences of the
      present results would be a reduction of the strength of this potential source of
      carboxylic acids in the atmosphere.

PMID- 16571051
TI  - Relationship between the time-dependence of a transient-state kinetic isotope
      effect and the location of complexes in a reaction sequence.
AB  - We prove here a new transient-state kinetic rule which states that the ratios of
      the first derivatives of kinetic isotope effect time courses, extrapolated to
      zero time, provide integral values which specify the precise step number in the
      reaction sequence in single isotope substituted reactions. This rule defines such
      absolute numbers even where the steps involved are too fast to provide measurable
      concentrations of intermediates and when the full reaction sequence is unknown.

PMID- 16571052
TI  - High-level coupled-cluster methods for electron spin resonance spectra: on the
      experimental spectrum of the silacyclobutane radical cation.
AB  - The silacyclobutane radical cation is a prototype intermediate in chemical
      reactions involving Si based organic molecules. In the interest of its full
      characterization, the experimentally determined isotropic hyperfine coupling
      constants of the hydrogens in silacyclobutane radical cation (c-SiC(3)(+)) have
      raised some interesting questions, leading to different interpretations of the
      spectrum. To help resolve this discrepancy, we report very high-level theoretical
      results with coupled-cluster theory using its analytical, response density matrix
      procedure, and recently proposed basis sets that are specific to ESR. The
      detailed studies of geometries, basis set effects, and electron correlation tend
      to support the B3LYP/6-31G-based reassignment of the ESR spectrum of the c
      SiC(3)(+) radical cation by Fangstrom et al.

PMID- 16571053
TI  - Reaction coordinate analysis of the S2-S1 internal conversion of phenylacetylene.
AB  - The reaction coordinate of the S(2)-S(1) internal conversion (IC) of
      phenylacetylene (PA) was analyzed using the ab initio complete active space self
      consistent field (CASSCF) method. In the first process after electronic
      excitation into S(2), the aromatic benzene ring is transformed into a nonaromatic
      quinoid structure. The ethynyl part (-C[triple bond]CH) takes an incomplete
      allenoid structure in which the CC bond elongates to an intermediate value
      between typical C[triple bond]C triple and C=C double bonds, but the bend angle
      of -CCH is 180 degrees . In the second process, PA takes a complete allenoid
      structure with an out-of-plane location of the beta-H atom (i.e., the H atom of
      the ethynyl part) and a further elongation of the CC bond so that PA is most
      stable in S(2) (S(2)-bent). The conical intersection between S(2) and S(1)
      (S(2)/S(1)-CIX) is located near the S(2)-bent geometry and is slightly unstable
      energetically. After transition at S(2)/S(1)-CIX, PA quickly loses both quinoid
      and allenoid structures and recovers the aromaticity of the benzene ring in S(1).
      Analysis of the dipole moment along the reaction coordinate shows that the weak
      electron-withdrawing group of the ethynyl part in S(0) suddenly changes into an
      electron-donating group in S(2) after the main transition of S(0)-S(2). The
      photoinduced change of the dipole moment is a driving force to the formation of a
      quinoid structure in S(2). Regarding the benefit of the reaction coordinate
      analysis of the multidimensional potential energy surfaces of PA, the present
      picture of the IC process is much more elaborate than our previous representation
      (Amatatsu, Y.; Hasebe, Y. J. Phys. Chem. A 2003 107, 11169-11173). Vibrational
      analyses along the reaction coordinate were also performed to support a time
      resolved spectroscopic experiment on the S(2)-S(1) IC process of PA.

PMID- 16571054
TI  - Conformational stability of a model macrocycle tetraamide: an ab initio study.
AB  - Ab initio calculations are carried out to investigate the conformational
      stability of a model macrocyle tetraamide. The four amide groups in the selected
      model are present in the sequence: -(O=CNH)-Ph-(NHC=O)-CH=CH-(O=CNH)-Ph-(NHC=O)
      CH=CH-. In this sequence, two phenyl rings and two ethene groups act as bridges
      between the amide units. Each amide motif bonds to a phenyl ring through its
      amide nitrogen and to an ethene group through its amide carbon. Four clearly
      distinct minimum-energy conformations are found upon full geometry optimization
      using the B3LYP/6-31+G(d) method. Frequency calculations using the same method
      confirm that the four conformations are indeed minima in the macrocycle potential
      energy surface. Relative to the most stable conformer, the other conformations
      are higher in energy by 0.86, 2.09, and 9.17 kcal/mol, respectively, at the MP2/6
      31+G(d,p) level. The stability of the macrocycle conformations is correlated
      primarily to the existence and strength of intramolecular N-H...O=C hydrogen
      bonds. Additional stability to the conformations is found to come from weak Ph
      H...O=C hydrogen bonding between a carbonyl oxygen and a hydrogen atom of a
      phenyl group. Solvent effects play an important role in the relative energies of
      the various conformations, as indicated by the simple SCRF = dipole model
      calculations for the case of aqueous solution.

PMID- 16571055
TI  - Mechanisms of the reactions of W AND W+ with H2O: computational studies.
AB  - The mechanism of the reactions of W and W(+) with the water molecule have been
      studied for several lower-lying electronic states of tungsten centers at the
      CCSD(T)/6-311G(d,p)+SDD and B3LYP/6-31G(d,p)+SDD levels of theory. It is shown
      that these reactions are essentially multistate processes, during which lower
      lying electronic states of the systems cross several times. They start with the
      formation of initial prereaction M(H(2)O) complexes with M-H(2)O bonding energies
      of 9.6 and 48.2 kcal/mol for M = W and W(+), followed by insertion of the metal
      center into an O-H bond with 20.0 and 53.3 kcal/mol barriers for neutral and
      cationic systems, respectively. The overall process of M + H(2)O --> t-HM(OH) is
      calculated to be highly exothermic, 48.4 and 48.8 kcal/mol for M = W and W(+).
      From the HM(OH) intermediate the reaction may proceed via several different
      channels, among which the stepwise HM(OH) --> HMO + H --> (H)(2)MO and concerted
      HM(OH) --> (H)(2)MO pathways are more favorable and can compete (energetically)
      with each other. For the neutral system (M = W), the concerted process is the
      most favorable, whereas for the charged system (M = W(+)), the stepwise pathway
      is slightly more favorable. From the energetically most favorable intermediate
      (H)(2)MO the reactions proceed via H(2)-molecule formation with a 53.1 kcal/mol
      activation barrier for the neutral system. For the cationic system, H-H formation
      and dissociation is an almost barrierless process. The overall reaction of W and
      W(+) with the water molecule leading to H(2) + MO formation is found to be
      exothermic by 48.2 and 39.8 kcal/mol, respectively. In the gas phase with the
      collision-less conditions the reactions W((7)S) + H(2)O --> H(2) +
      WO((3)Sigma(+)), and W(+)((6)D) + H(2)O --> H(2) + WO(+)((4)Sigma(+)) are
      expected to proceed via a 10.4 and 5.1 kcal/mol overall energy barrier
      corresponding to the first O-H dissociation at the TS1. On the basis of these
      PESs, we predict kinetic rate constants for the reactions of W and W(+) with
      H(2)O.

PMID- 16571056
TI  - A density functional study on beryllium-doped carbon dianion clusters CnBe2- (n =
      4-14).
AB  - Making use of the software of molecular graphics, we designed numerous models of
      C(n)()Be(2-) (n = 4-14). We carried out geometry optimization and calculation on
      vibration frequency by means of the B3LYP density functional method. After
      comparison of structure stability, we found that the ground-state isomers of
      C(n)()Be(2-) (n = 4-14) are linear with the beryllium atom located inside the
      C(n)() chain. When a side carbon chain is with an even number of carbon atoms, it
      is polyacetylene-like, whereas when a side chain is with an odd number of carbon
      atoms, it is cumulene-like. The C(n)Be(2-) (n = 4-14) clusters with an even
      number of carbon atoms are more stable than that with an odd number of carbon
      atoms, matching the peak pattern observed in accelerator mass spectrometry (AMS)
      and Coulomb Explosion Imaging (CEI) investigations of C(n)()Be(2-) (n = 4-14).
      The trend of such odd/even alternation is explained based on concepts of bonding
      characteristics, electronic configuration, electron detachment, and incremental
      binding energy.

PMID- 16571057
TI  - Methyl and phenyl substitution effects on the proton affinities of hydrides of
      first and second row elements and substituent effects on the proton affinities of
      ring carbons in benzene: a DFT study.
AB  - Theoretical calculations using B3LYP density functional theory (DFT) with the 6
      311++G(d,p) basis set have been performed to determine proton affinities (PAs) of
      a series of H-X compounds and the corresponding methyl- (H(3)C-X) and phenyl- (Ph
      X) substituted derivatives with a variety of proton acceptor atoms, such as C, O,
      N, F, Si, P, S, Cl, etc. Our results illustrate an interesting substituent effect
      on PAs. The PAs of ring carbon atoms for a series of monosubstituted benzene
      molecules (Y-C(6)H(5); Y = F, Cl, CH(3), OCH(3), NH(2), PH(2), OH, SH, SiH(3),
      CN, CF(3), and NO(2)) have also been estimated. Correlations between proton
      affinities of H-X, H(3)C-X, and Ph-X and substituent effects on the PAs of the
      ring carbon atoms for a series of monosubstituted benzene molecules have been
      studied. It has been observed that substituent effects on the PAs of the ring
      carbon atoms follow a good Hammett-type correlation.

PMID- 16571058
TI  - Electro-optical parameters of bond polarizability model for aluminosilicates.
AB  - Electro-optical parameters (EOPs) of bond polarizability model (BPM) for
      aluminosilicate structures were derived from quantum-chemical DFT calculations of
      molecular models. The tensor of molecular polarizability and the derivatives of
      the tensor with respect to the bond length are well reproduced with the BPM, and
      the EOPs obtained are in a fair agreement with available experimental data. The
      parameters derived were found to be transferable to larger molecules. This
      finding suggests that the procedure used can be applied to systems with partially
      ionic chemical bonds. The transferability of the parameters to periodic systems
      was tested in molecular dynamics simulation of the polarized Raman spectra of
      alpha-quartz. It appeared that the molecular Si-O bond EOPs failed to reproduce
      the intensity of peaks in the spectra. This limitation is due to large values of
      the longitudinal components of the bond polarizability and its derivative found
      in the molecular calculations as compared to those obtained from periodic DFT
      calculations of crystalline silica polymorphs by Umari et al. (Phys. Rev. B 2001,
      63, 094305). It is supposed that the electric field of the solid is responsible
      for the difference of the parameters. Nevertheless, the EOPs obtained can be used
      as an initial set of parameters for calculations of polarizability related
      characteristics of relevant systems in the framework of BPM.

PMID- 16571059
TI  - Theoretical study of structure, vibrational frequencies, and electronic spectra
      of polychlorinated dibenzo-p-dioxins.
AB  - The structure, vibrational frequencies, and excited states of 2,3,7,8-tetrachloro
      , 1,4,6,9-tetrachloro-, and octachlorodibenzo-p-dioxin (2,3,7,8-TCDD, 1,4,6,9
      TCDD, and OCDD) were studied via complete active space SCF followed by the
      multireference second-order perturbative approach (CASSCF/CASPT2), as well as the
      time-dependent density functional theory (TD-B3LYP). The cc-pVDZ basis set and
      the full pi-electron active spaces of 16 electrons in 14 active orbitals were
      employed. Whereas 2,3,7,8-TCDD assumes a planar D(2)(h)() minimum, 1,4,6,9-TCDD
      and OCDD are slightly folded exhibiting the C(2)(v)() symmetry. The extra
      stabilization due to the folding is very small. In all three isomers the highly
      intensive band system in the 200-240 nm region is dominated by the transitions to
      the 2(1)B(2u) and 3(1)B(2u) states with by far the largest oscillator strengths.
      The low-intensity absorptions in the 280-320 nm region can be attributed to the
      1(1)B(2u) <-- 1(1)A(g), with possible contribution of the vibronically allowed
      2(1)A(g) <-- 1(1)A(g) transition. Both CASPT2 and TD-B3LYP convincingly predict
      1(3)B(3g) to be the lowest lying triplet state, which contradicts the
      experimental assignments. Calculated harmonic wavenumbers and absorption spectra
      agree well with the experimental data, and are sufficiently distinct to allow for
      an unambiguous identification of the three isomers.

PMID- 16571060
TI  - Molecular fragments in density functional theory.
AB  - The second-order density functional approach to the partitioning of the molecular
      density of Cedillo, Chattaraj, and Parr (Int. J. Quantum Chem. 2000, 77, 403-407)
      is used, together with a local assumption for the function that projects the
      total density into its components, to show that the distribution function adopts
      a stockholders form, in terms of the local softness of the isolated fragments,
      and that the molecular Fukui function is distributed in the molecular fragments
      in the same proportion as the electronic density.

PMID- 16571062
TI  - The electronic structure of alkali aurides. A four-component Dirac-Kohn-Sham
      study.
AB  - Spectroscopic constants, including dissociation energies, harmonic and anharmonic
      vibrational frequencies, and dipole moments, are calculated for the complete
      alkali auride series (LiAu, NaAu, KAu, RbAu, CsAu). The four-component
      formulation of relativistic density functional theory has been employed in this
      study, using the G-spinor basis sets implemented recently in the program BERTHA.
      The performance of four standard nonrelativistic density functionals employed is
      investigated by comparing the results with the best available theoretical and
      experimental data. The present work provides the first theoretical predictions on
      the molecular properties of RbAu. The intermetallic bond that occurs in the
      alkali auride series is highly polar and is characterized by a large charge
      transfer from the alkali metals to gold. The extent of this electron transfer has
      been investigated using several different charge analysis methods, enabling us to
      reach some general conclusions on their relative performance. We further report a
      detailed analysis of the topological properties of relativistic electron density
      in the bonding region, discussing the features of this approach which
      characterize the nature of the chemical bond. We have also computed the fully
      relativistic density for the alkali halides MBr and MI (M = Li, Na, K, Rb, and
      Cs). The comparative study shows that, on the basis of several topological
      properties and the variation in bond lengths, the gold atom behaves similarly to
      a halogen intermediate between Br and I.

PMID- 16571061
TI  - Bilateral, difunctional nanosphere aggregates and their assembly mediated by
      polymer chains.
AB  - We have developed an efficient method for producing difunctional, bilateral
      nanospheres. A monolayer of nanoparticles was prepared followed by deposition of
      a thin layer of metal. By varying the base particle and metal deposited,
      bilateral nanoparticles were formed. The different regions of the nanoparticles
      were selectively functionalized with polymer linkers containing specific terminal
      groups, thereby creating bilateral, difunctional nanoparticles. Subsequent
      covalent cross-linking of different nanoparticles enabled the formation of stable
      architectures with programmed hierarchy and controlled chemical composition.

PMID- 16571063
TI  - Transition-state characterization of the ammonia ionization process in aqueous
      solution via the free-energy gradient method.
AB  - For the ionization process of ammonia in aqueous solution, the transition-state
      (TS) structure was fully optimized for the first time on the free-energy surface
      (FES) by applying the free-energy gradient (FEG) method combined with a hybrid
      quantum mechanical and molecular mechanical molecular dynamics (QM/MM-MD) method.
      In aqueous solution, the ionization process was found to proceed by way of a
      clear TS (R(N1-H5) = 1.512 A), which does not exist in the gas phase. The free
      energy (FE) of activation for ionization obtained was 14.7 kcal/mol, within the
      classical approximation, via the QM/MM-MD FEG method, and is found to be in good
      agreement with 9.57 kcal/mol estimated from the TS theory using the experimental
      value of the rate constant. Apart from the dynamic correction, it is indicated
      that the theoretical value would be improved to be 10.28 kcal/mol if the
      electronic-state calculation could be executed at the B3LYP/6-31G(d) level of
      theory.

PMID- 16571064
TI  - Theoretical study of the complexes of horminone with Mg2+ and Ca2+ ions and their
      relation with the bacteriostatic activity.
AB  - The coordination of the horminone molecule with hydrated magnesium and calcium
      divalent ions was studied by means of the density functional theory. All-electron
      calculations were performed with the B3LYP/6-31G method. The first layer of the
      water molecules surrounding the metallic cations was included. It was found that
      the octahedral [horminone(O(a)-O(d))-Mg-(H(2)O)(4)](2+) complex is more stable
      than [Mg(H(2)O)(6)](2+). That is, horminone is able to displace two water units
      from the hexahydrated complex. This behavior does not occur for Ca(2+).
      Consistently, [horminone(O(a)-O(d))-Mg-(H(2)O)(4)](2+) has a greater metal-ligand
      binding energy than [horminone(O(a)-O(d))-Ca-(H(2)O)(4)](2+). The preference of
      horminone by Mg(2+) is enlightened by these results. Moreover, its electronic
      structure, as shown by huge changes in the atomic populations, is strongly
      perturbed by Mg(2+). Indeed, horminone, bonded to [Mg(H(2)O)(4)](2+), is able to
      cross the bacterial membrane cell. Once inside, [horminone(O(a)-O(d))-Mg
      (H(2)O)(4)](2+) binds to rRNA phosphate groups yielding [horminone(O(a)-O(d))-Mg
      (H(2)O)(PO(4)H(2))(PO(4)H(3))(2)](+). These results give insights into how
      horminone may inhibit the initial steps of protein synthesis. The stability of
      the studied systems is accounted for in terms of the calculated structural and
      electronic properties: Mg-O and Ca-O bond lengths, charge transfers, and binding
      energies.

PMID- 16571065
TI  - Perfluorobutane sulfonic acid hydration and interactions with O2 adsorbed on Pt3.
AB  - The side chain of NAFION, a proton conductive membrane used as electrolyte in low
      temperature fuel cells, is modeled with perfluorobutane sulfonic acid. Density
      functional theory is used to characterize structures and energetics of hydration
      of the model system interacting with a proton solvated with up to 24 water
      molecules and analyze interactions of some of these hydrated complexes with O(2)
      adsorbed on Pt(3). It is found that at least three water molecules are needed to
      ionize the sulfonic acid, and higher degrees of hydration induce the formation of
      cages where the water molecules are held together via complex hydrogen-bond
      networks. The interaction between the complex formed by the ionized acid and the
      hydrated proton, in contact with a bridge-adsorbed O(2)-Pt(3), promotes the
      protonation of the adsorbed O(2). Upon protonation, the O(2)-Pt(3) system evolves
      from hydrophobic to hydrophilic behavior, which may facilitate further
      interfacial contact.

PMID- 16571066
TI  - Planar tetracoordinated silicon in silicon carbonyl complexes: a DFT approach.
AB  - Recently, some works have focused attention on the reactivity of the silicon atom
      with closed-shell molecules. With CO, silicon may form a few relatively stable
      compounds, i.e., Si(CO), Si(CO)(2), and Si[C(2)O(2)], while the existence of
      polycarbonyl (n > 2) silicon complexes has been rejected by current literature.
      In this paper, the reaction of silicon with carbonyl has been reinvestigated by
      density functional calculations. It has been found that the tetracoordinated
      planar Si(CO)(4) complex is thermodynamically stable. In Si(CO), silicon
      carbonyl, and Si(CO)(2), silicon dicarbonyl, the CO moieties are datively bonded
      to Si, and Si[C(2)O(2)], c-silicodiketone, is similar to the compounds formed by
      silicon and ethylene; Si(CO)(4), silicon tetracarbonyl, may be viewed as a
      resonance between the extreme configurations (CO)(2)Si + 2CO and 2CO + Si(CO)(2).
      A detailed orbital analysis has shown that the Si bonding with four CO is
      consistent with the use of sp(2)d-hybridized orbitals on silicon, giving rise to
      a planar structure about Si.

PMID- 16571067
TI  - Influence of geometry relaxation on the energies of the S1 and S2 states of
      violaxanthin, zeaxanthin, and lutein.
AB  - Precise knowledge of the excitation energies of the lowest excited states S(1)
      and S(2) of the carotenoids violaxanthin, lutein, and zeaxanthin is a
      prerequisite for a fundamental understanding of their role in light harvesting
      and photoprotection during photosynthesis. By means of density functional theory
      (DFT) and time-dependent DFT (TDDFT), the electronic and structural properties of
      the ground and first and second excited states are studied in detail. According
      to our calculations, all-s-cis-zeaxanthin and s-cis-lutein conformers possess
      lower total ground-state energies than the corresponding s-trans conformers.
      Thus, only s-cis isomers are probably physiologically relevant. Furthermore, the
      influence of geometric relaxation on the energies of the ground state and S(1)
      and S(2) states has been studied in detail. It is demonstrated that the energies
      of these states change significantly if the carotenoid adopts the equilibrium
      geometry of the S(1) state. Considering these energetic effects in the
      interpretation of S(1) excitation energies obtained from fluorescence and
      transient absorption spectroscopy shifts the S(1) excitation energies about 0.2
      eV to higher energy above the excitation energy of the chlorophyll a.

PMID- 16571068
TI  - Trajectory approach to the mode-selected photodissociation of CS2.
AB  - Through the study of photodissociation events in the CS(2) molecule that
      originate in various selected vibrational modes, but terminate in the same final
      predissociation state, we looked for the evidence that photodissociation
      processes can depend on the initial conditions. Such dependence would not occur
      within RRKM theory, because of its statistical assumptions. The experimental
      results were compared with trajectory calculations in normal mode coordinates, in
      which initial conditions were given in terms of coordinates and momenta. We have
      found that the photodissociation rate for events originating in the combination
      nu(1), nu(2) mode is higher than that for events from the pure nu(2) mode, and
      shows a large variation along the vibrational progression. The experimental
      observations agree with the trajectory calculations. In addition, the trajectory
      calculations predict that photodissociation events initiated at small values of
      the vibrational coordinates result in larger dissociation rates at low excess
      energy above the dissociation limit, while events from large values of the
      coordinates result in larger dissociation rates at high excess energies.

PMID- 16571069
TI  - Thermal reactions of benzoxazole. Single pulse shock tube experiments and quantum
      chemical calculations.
AB  - The thermal decomposition of benzoxazole diluted in argon was studied behind
      reflected shock waves in a 2 in. i.d. single-pulse shock tube over the
      temperature range 1000-1350 K and at overall densities of approximately 3 x 10(
      5) mol/cm(3). Two major products, o-hydroxybenzonitrile at high concentration and
      cyclopentadiene carbonitrile (accompanied by carbon monoxide) at much lower
      concentration, and four minor fragmentation products resulting from the
      decomposition were found in the postshock samples. They were, in order of
      decreasing abundance, benzonitrile, acetylene, HCN, and CH=C-CN and comprised of
      only a few percent of the overall product distribution. Quantum chemical
      calculations were carried out to determine the sequence of the unimolecular
      reactions that led to the formation of o-hydroxybenzonitrile and cyclopentadiene
      carbonitrile, the major products of the thermal reactions of benzoxazole. A
      potential energy surface leading directly from benzoxazole to cyclopentadiene
      carbonitrile could not be found, and it was shown that the latter is formed from
      the product o-hydroxybenzonitrile. In order that cyclopentadiene carbonitrile be
      produced, CO elimination and ring contraction from a six- to a five-membered ring
      must take place. A surface where CO elimination occurs prior to ring contraction
      was found to have very high barriers compared to the ones where ring contraction
      occurs prior to CO elimination and was not considered in our discussion. Rates
      for all the steps on the various surfaces were evaluated, kinetic schemes
      containing these steps were constructed, and multiwell calculations were
      performed to evaluate the mole percent of the two major products as a function of
      temperature. The agreement between the experimental results and these
      calculations, as shown graphically, is very good.

PMID- 16571072
TI  - Monkey embryonic stem cells differentiate into adipocytes in vitro.
AB  - Production of functional adipocytes is important in adipocyte research and
      regenerative medicine. In this paper, we describe the differentiation of monkey
      embryonic stem (ES) cells into insulin-responsive adipocytes. Treatment of
      embryoid body (EB) outgrowth with adipogenic hormones induced the expression of
      adipocyte-specific genes, such as PPARgamma, C/EBPalpha, aP2, insulin receptor,
      and GLUT4. Expression of adipocytokines, leptin and adiponectin, was also
      detected. Furthermore, translocation of GLUT4 was observed by insulin stimulation
      in differentiated adipocytes. These results suggested that monkey ES cells can be
      a useful tool for studying adipogenesis in primate.

PMID- 16571073
TI  - Modifications to improve the efficiency of zona-free mouse nuclear transfer.
AB  - In the present study, some modifications were made to the zona-free nuclear
      transfer technique in the mouse in order to achieve greater efficiency. Firstly,
      a 1-h interval was allowed between cumulus removal and zona pellucida digestion.
      Secondly, acid Tyrode's was selected for zona pellucida removal, because contrary
      to pronase, it allows embryo survival during parthenogenic activation in the
      absence of calcium. Even when the exposure time to pronase was reduced to as
      little as 1 min or washed with fetal calf serum to inhibit the enzyme, the
      percentage of lysis during activation in the absence of calcium was still very
      high. Thirdly, electrofusion was performed at room temperature (21 degrees C),
      instead of 30 degrees C as in our previous experiments. Finally, embryos were
      cultured in groups of 12-15, instead of individually, using a "well of the wells"
      system during activation and culture. When compared, parthenogenic activated
      control embryos showed an increase in the development to blastocyst when cultured
      in pairs instead of individually. By the end of the experiments and using
      embryonic stem (ES) cells, there was a significant increase in fusion rate (1.5
      fold increase) and in development to morula/blastocyst from cleaved reconstructed
      embryos (1.5-fold increase) when compared with the results before the
      modifications. A 2.4-fold increase in overall efficiency was achieved from the
      oocyte to morula/blastocyst stages.

PMID- 16571074
TI  - Physiologic oxygen enhances human embryonic stem cell clonal recovery and reduces
      chromosomal abnormalities.
AB  - Human embryonic stem cells (hESC) have great potential in regenerative medicine,
      provided that culture systems are established that maintain genomic integrity.
      Here we describe a comparison of the effects of culture in either physiologic
      oxygen (2%) or room oxygen (21%) on the hESC lines, H1, H9, and RH1. Physiologic
      oxygen enabled an average sixfold increase in clone recovery across the hESC
      lines tested (p < 0.001). FACS analysis showed that cells cultured in physiologic
      oxygen were significantly smaller and less granular. No significant changes had
      occurred in levels of SSEA4, SSEA1, TRA-1-60, or TRA-1-81. While karyotypic
      normalcy was maintained in both H1 and H9, the frequency of spontaneous
      chromosomal aberrations was significantly increased in room oxygen. This increase
      was not observed in physiologic oxygen. These results clearly demonstrate that
      physiologic oxygen culture conditions are indispensable for robust hES clone
      recovery and may enhance the isolation of novel hES lines and transgenic clones.

PMID- 16571075
TI  - Recombinant human albumin supports development of somatic cell nuclear transfer
      embryos in mice: toward the establishment of a chemically defined cloning
      protocol.
AB  - Culturing embryos in different media is a useful approach to characterize their
      nature in regard to "memory" of the donor nucleus and its "reprogramming" after
      somatic cell nuclear transfer (SCNT). However, efforts to elucidate the
      mechanisms of reprogramming are seriously undermined when embryo culture
      conditions are not completely defined. Using recombinant human albumin (rHA) is a
      step toward establishing defined culture conditions for mouse cloning.
      Recombinant HA supports blastocyst formation of cumulus cell-derived clones at a
      rate comparable with two types of bovine serum albumin (BSA); following transfer
      of blastocysts to the genital tract, rates of development to midgestation (10.5
      dpc) were indistinguishable. rHA also supports the derivation of germline
      competent embryonic stem (ES) cells from SCNT blastocysts at a substantial rate
      compared with BSA counterparts and with zygotic blastocysts. Unlike the
      developmental parameters, the gene expression patterns of clones cultured in rHA
      or BSA were not superimposed; identical patterns were observed for zygotic
      blastocysts in the two albumins. In summary, the present study demonstrates that
      (1) rHA can replace BSA, proving a defined protein source for SCNT in mice; (2)
      although using rHA is similar to BSA, it is not equal (rHA leaves a mark on gene
      expression of clones but not zygotes). Future studies that investigate
      reprogramming after SCNT will need to consider not only the implications of
      culture media for cloning but also the supplement choice.

PMID- 16571076
TI  - Analysis of development-related gene expression in cloned bovine blastocysts with
      different developmental potential.
AB  - The high incidence of abnormalities in cloned calves is a most serious problem
      for bovine somatic cell nuclear transfer (NT) technology. Because there is little
      information on the differences in mRNA expression in cloned blastocysts with
      donor cells of different sex and origin, we compared development-related gene
      expression in two types of cloned bovine blastocysts with different potentials to
      develop into normal calves, a female adult cumulus cell line (high potential to
      develop into live calves) and a male fibroblast cell line (low potential to
      develop into live calves) to examine the correlation between the normality of
      cloned calves and blastocyst mRNA expression patterns. We analyzed 12 genes
      involved in apoptosis, growth factor signaling, metabolism, and DNA methylation
      in blastocysts originating from two types of donor cells and in vitro-fertilized
      blastocysts using quantitative real-time polymerase chain reaction. Expression of
      the pro-apoptotic Bax gene and anti-apoptotic Bcl-2 and Glut-1 genes in
      fibroblast-derived blastocysts was significantly higher than in cumulus cell
      derived and in vitro-fertilized blastocysts. The high Bcl-2 and Glut-1 gene
      expression suggests that some embryonic cells with damaged DNA in fibroblast
      derived blastocysts are not removed, and their descendants later manifest
      abnormal placenta or fetus formation. Transfer of pre-selected cloned blastocysts
      into recipients is required, however, to determine whether the expression pattern
      of these apoptosis-related genes reflects differences in the potential to develop
      into normal calves.

PMID- 16571077
TI  - Transfer of inner cell mass cells derived from bovine nuclear transfer embryos
      into the trophoblast of bovine in vitro-produced embryos.
AB  - Presence of placental tissues from more normal noncloned embryos could reduce the
      pregnancy failure of somatic cloning in cattle. In this study, inner cell mass
      (ICM) cells of in vitro-produced (IVP) embryos was replaced with those of nuclear
      transfer (NT) embryos to reconstruct bovine blastocysts with ICM and trophoblast
      cells from NT and IVP embryos, respectively. A total of 65 of these reconstructed
      embryos were nonsurgically transferred to 20 recipient beef females. Of those,
      two females were diagnosed pregnant by ultrasonography on day 30 of gestation.
      One pregnancy was lost at 60-90 days of gestation, and the other recipient cow
      remained pregnant at day 240 of gestation; however, this female died on day 252
      of gestation. Gross pathology of the internal organs of the recipient female, a
      large fetus, and a large placental tissue mass suggested the massive size of the
      fetus and placental tissue were likely involved in terminating the life of the
      recipient female. Biopsy samples were harvested from the skin of the dead
      recipient cow, the fetus and from cotyledonary tissue. Microsatellite DNA
      analysis of these samples revealed that the genotype of the fetus was the same as
      that of the NT donor cells and different from that of the recipient cow.
      Correspondingly, neither the fetus nor recipient cow had the same genotype with
      that of the fetal cotyledonary tissue. These results present the first known
      documented case of a bovine somatic NT pregnancy with nonclone placental tissues
      after transfer of a blastocyst reconstructed by a microsurgical method to
      exchange of ICM cells and trophoblast tissue between NT and IVP blastocysts.

PMID- 16571079
TI  - Is consensus a good thing in the management of thyroid nodules?

PMID- 16571078
TI  - Demecolcine-assisted enucleation for bovine cloning.
AB  - The present study demonstrated that demecolcine treatment for at least 30 min
      produces a membrane protrusion in metaphase II-stage bovine oocytes. The maternal
      chromosome mass is condensed within the protrusion, which makes it easy to remove
      the maternal chromosomes for nuclear transfer (NT). Maturation promoting factor
      activity, but not mitogen-activated protein kinase activity, increased up to 30%
      in oocytes during demecolcine treatment. One normal healthy calf was obtained
      after transfer of four NT blastocysts produced following demecolcine treatment.
      Demecolcine treatment did not increase the potential of NT oocytes to develop
      into blastocysts. The present study demonstrated that chemically-assisted removal
      of chromosomes is effective for bovine cloning.

PMID- 16571080
TI  - The endocrinologists' view of ultrasound guidelines for fine needle aspiration.

PMID- 16571081
TI  - Management of thyroid nodules detected at sonography: Society of Radiologists in
      Ultrasound Consensus Conference Statement.

PMID- 16571082
TI  - Regulation of nuclear coactivator and corepressor expression in mouse cerebellum
      by thyroid hormone.
AB  - Thyroid hormone (TH) has an important role in central nervous system development.
      TH action is mediated by a number of transcription factors including thyroid
      hormone receptors (TRs) in combination with a group of coregulators that can
      either activate (coactivators) or repress (corepressors) transcription in the
      presence of TH. The aims of this report were to determine if regulation of the
      corepressor Hairless (Hr) by TH was TR-isoform- mediated in neonatal cerebellum
      and to determine if other cerebellar corepressors (SMRT and NCoR) and
      coactivators (SRC family) are also regulated by TH. In order to study this we
      examined 14-day-old and adult knockout mice that lack expression of the TRbeta or
      TRalpha isoforms and measured mRNA expression in untreated, hypothyroid and TH
      treated young mouse pups. TH-treated wild-type and TRbeta-deficient mice
      demonstrated upregulation of Hr by 22.8- +/- 8.6- and 11.8- +/- 3.6-fold
      respectively, which was not upregulated in TRalpha-deficient mice. In wild-type
      mice, TH treatment results in a reciprocal decrease (61%) in the coactivator SRC
      1. These changes were not observed in adult mouse cerebellum. No effect was seen
      with NCoR and SRC-3 expression. SMRT was 3-fold increased in TH treatment of only
      wild-type mouse pups. We conclude that (1) TRalpha is the major TR regulating Hr
      expression in the cerebellum of young mouse pups; (2) TH upregulates Hr and SMRT
      and downregulates SRC-1; (3) NcoR and SRC-3 may not be regulated by TH in the
      cerebellum at the transcriptional level; and (4) autoregulation of TH action may
      be mediated through TH-dependent expression of the cofactors necessary for TH
      action in the cerebellum and may be developmentally specific.

PMID- 16571083
TI  - Selective pharmacologic inhibition of c-Jun NH2-terminal kinase radiosensitizes
      thyroid anaplastic cancer cell lines via induction of terminal growth arrest.
AB  - CONTEXT: The high radioresistance of anaplastic thyroid cancer (ATC) and cultured
      ATC cells stipulates for the means of increasing their radiosensitivity. It has
      been shown that c-Jun NH(2)-terminal kinase (JNK) activation is one of the
      manifestations of radiation response in ATC cells. OBJECTIVE: Assessment of the
      effect of selective JNK inhibition on ATC cell radiosensitivity and clarification
      of the associated mechanisms. RESULTS: The JNK inhibitor markedly suppressed ATC
      cell growth in a reversible cytostatic manner. The combination treatment with JNK
      inhibitor plus ionizing radiation induced a significant decrease in clonogenic
      survival of irradiated cells as compared with either singular treatment. The
      effect was not due to apoptosis of exposed cells but to a profound senescence
      like terminal growth arrest occurring irrespectively of cells' p53 mutational
      status. Postradiational DNA damage repair was also significantly compromised in
      the presence of SP600125. CONCLUSIONS: JNK signaling is an essential component of
      ATC cell proliferation and survival after radiation therapy. Hence,
      pharmacological interference with JNK pathway in combination with radiotherapy
      may be a promising treatment of ATC.

PMID- 16571084
TI  - Human thyroid autoantigens and proteins of Yersinia and Borrelia share amino acid
      sequence homology that includes binding motifs to HLA-DR molecules and T-cell
      receptor.
AB  - We previously reported that the spirochete Borrelia burgdorferi could trigger
      autoimmune thyroid diseases (AITD). Subsequently, we showed local amino acid
      sequence homology between all human thyroid autoantigens (human thyrotropin
      receptor [hTSH-R], human thyroglobulin [hTg], human thyroperoxidase [hTPO], human
      sodium iodide symporter [hNIS]) and Borrelia proteins (n = 6,606), and between
      hTSH-R and Yersinia enterocolitica (n = 1,153). We have now updated our search of
      homology with Borrelia (n = 11,198 proteins) and extended our search on Yersinia
      to the entire species (n = 40,964 proteins). We also searched the homologous
      human and microbial sequences for peptide-binding motifs of HLA-DR molecules,
      because a number of these class II major histocompatibility complex (MHC)
      molecules (DR3, DR4, DR5, DR8, and DR9) are associated with AITD. Significant
      homologies were found for only 16 Borrelia proteins (5 with hTSH-R, 2 with hTg, 3
      with hTPO, and 6 with hNIS) and only 19 Yersinia proteins (4 with hTSH-R, 2 with
      hTg, 2 with hTPO, and 11 with hNIS). Noteworthy, segments of thyroid autoantigens
      homologous to these microbial proteins are known to be autoantigenic. Also, the
      hTSH-R homologous region of one Borrelia protein (OspA) contains an
      immunodominant epitope that others have found to be homologous to hLFA-1. This is
      of interest, as the hLFA-1/ICAM-1 ligand/receptor pair is aberrantly expressed in
      the follicular cells of thyroids affected by Hashimoto's thyroiditis. A computer
      assisted search detected antigenic peptide binding motifs to the DR molecules
      implicated in AITD. In conclusion, our in silico data do not directly demonstrate
      that Borrelia and Yersinia proteins trigger AITD but suggest that a restricted
      number of them might have the potential to, at least in persons with certain HLA
      DR alleles.

PMID- 16571085
TI  - Lack of a genetic association between the CTLA-4 gene and Graves' disease in
      Koreans.
AB  - Graves' disease (GD) is a complex autoimmune thyroid disease with a strong
      genetic component. The cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene,
      which encodes a negative regulator of the T-lymphocyte immune response, has been
      reported to be associated and/or linked to GD. Therefore, in order to determine
      the contribution of CTLA-4 in GD in Koreans, we genotyped the five single
      nucleotide Polymorphisms (SNPs) of the CTLA-4 gene, including +49, CT60, JO31,
      JO30, and JO27-1 in Korean spatients with GD and healthy controls. Two hundred
      seventy-eight Korean patients with GD from the Thyroid Clinic and 472 healthy
      controls from the Health Screening Center of Samsung Medical Center were enrolled
      in this study. The +49A/G polymorphism of the CTLA-4 gene exon 1 was sequenced
      directly and the genotyping of the remaining 4 SNPs was accomplished using a
      Snapshot. In addition, the association of haplotypes with a combination of the
      above markers was also examined in 278 Korean patients with GD and 472 controls.
      The results showed that there was no significant positive association between any
      individual SNP or haplotype comprising of the four 3 untranslated region (UTR)
      SNPs (CT60, JO31, JO30, and JO27-1) and GD. These data provide little support for
      CTLA-4 to play a role in the genetic predisposition to GD in Koreans. However, it
      will be necessary to validate or replicate this association in other independent
      large-size ethnic groups.

PMID- 16571086
TI  - Lack of association of interleukin-18 gene polymorphisms with susceptibility of
      Japanese populations to Graves' disease or Graves' ophthalmopathy.
AB  - OBJECTIVE: To investigate whether polymorphisms of interleukin (IL)-18 gene
      confer susceptibility to Graves' disease (GD) and Graves' ophthalmopathy (GO).
      DESIGN: We performed a case control study on polymorphisms of IL-18 gene in
      Japanese patients with GD (n = 435), and healthy control subjects without
      antithyroid autoantibodies or family history of autoimmune disorders (n = 255).
      The C-4675G, C-607A, and G-137C polymorphisms in the promoter region and A105C
      (exon 5) polymorphism were determined by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) using restriction enzymes, sequence
      specific PCR, and PCR-direct sequencing methods. RESULTS: None of the
      polymorphisms in the IL-18 gene were associated with development of Graves'
      disease. The CC genotype and C allele frequencies of IL-18 gene G-137C
      polymorphism tended to be greater in patients with ophthalmopathy than in
      patients without evident ophthalmopathy. However, the differences were not
      statistically significant. Although there were three major haplotypes, none of
      the haplotypes were statistically associated with susceptibility to GD or
      ophthalmopathy. CONCLUSIONS: These results suggest that IL-18 gene polymorphisms
      are not major genetic factors for susceptibility to GD in a Japanese population.
      Further studies with adequate sized data set in the subset analyses for GO are
      needed.

PMID- 16571087
TI  - Effects of soy protein and soybean isoflavones on thyroid function in healthy
      adults and hypothyroid patients: a review of the relevant literature.
AB  - Soy foods are a traditional staple of Asian diets but because of their purported
      health benefits they have become popular in recent years among non-Asians,
      especially postmenopausal women. There are many bioactive soybean components that
      may contribute to the hypothesized health benefits of soy but most attention has
      focused on the isoflavones, which have both hormonal and nonhormonal properties.
      However, despite the possible benefits concerns have been expressed that soy may
      be contraindicated for some subsets of the population. One concern is that soy
      may adversely affect thyroid function and interfere with the absorption of
      synthetic thyroid hormone. Thus, the purpose of this review is to evaluate the
      relevant literature and provide the clinician guidance for advising their
      patients about the effects of soy on thyroid function. In total, 14 trials
      (thyroid function was not the primary health outcome in any trial) were
      identified in which the effects of soy foods or isoflavones on at least one
      measure of thyroid function was assessed in presumably healthy subjects; eight
      involved women only, four involved men, and two both men and women. With only one
      exception, either no effects or only very modest changes were noted in these
      trials. Thus, collectively the findings provide little evidence that in
      euthyroid, iodine-replete individuals, soy foods, or isoflavones adversely affect
      thyroid function. In contrast, some evidence suggests that soy foods, by
      inhibiting absorption, may increase the dose of thyroid hormone required by
      hypothyroid patients. However, hypothyroid adults need not avoid soy foods. In
      addition, there remains a theoretical concern based on in vitro and animal data
      that in individuals with compromised thyroid function and/or whose iodine intake
      is marginal soy foods may increase risk of developing clinical hypothyroidism.
      Therefore, it is important for soy food consumers to make sure their intake of
      iodine is adequate.

PMID- 16571089
TI  - Thyroid-stimulating hormone-stimulated fused positron emission
      tomography/computed tomography in the evaluation of recurrence in 131I-negative
      papillary thyroid carcinoma.
AB  - Fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)
      detects recurrence of papillary thyroid carcinoma (PTC) in thyroidectomized
      patients with elevated thyroglobulin (Tg) levels and negative (131)I-whole-body
      scans. This paper describes the utility of thyroid-stimulating hormone (TSH)
      stimulated fused FDG-PET/computed tomography (CT) scanning on our first 15
      patients of this population. METHODS: Patients were prepared for PET/CT imaging
      with thyroid hormone withdrawal (n = 7) or recombinant human TSH (n = 8). All
      other imaging before the PET/CT did not demonstrate evidence of recurrence.
      RESULTS: PET/CT scans revealed active foci in 9 patients, 4 prepared with
      hypothyroidism, and 5 with exogenous TSH. Positive results were demonstrated even
      in those with relatively low stimulated-TSH Tg values (13 and 14 microg/L). Six
      patients with positive PET/CT scans were treated surgically, yielding malignant
      tissue for 5 of those patients. CONCLUSION: PET/CT scans performed under TSH
      stimulation are an effective method of detecting of recurrence of PTC and direct
      surgical interventions, even in those with persistently elevated but relatively
      low Tg levels.

PMID- 16571088
TI  - The use of rapid parathyroid hormone assay in predicting postoperative
      hypocalcemia after total or completion thyroidectomy.
AB  - PURPOSE: To evaluate the rapid parathyroid hormone assay (rPTH) as a
      perioperative tool in predicting postoperative symptomatic hypocalcemia following
      thyroidectomy. METHODS: We conducted a prospective study of 69 patients
      undergoing total or completion thyroidectomy. Rapid PTH levels were obtained
      preoperatively, intraoperatively, and postoperatively upon arrival in the
      postanesthesia care unit (PACU). All patients were closely monitored
      postoperatively for the development of symptomatic or asymptomatic hypocalcemia.
      RESULTS: Of 60 patients (25%) undergoing thyroidectomy, 15 developed
      hypocalcemia, 7 (11.7%) were symptomatic, and 8 (13.3%) asymptomatic. An
      intraoperative rPTH level less than 12 pg/mL was 71% sensitive and 95% specific
      for predicting postoperative symptomatic hypocalcemia, whereas a PACU rPTH level
      less than 12 pg/mL was 100% sensitive and 92% specific. A greater than 75%
      decline in preoperative rPTH level when measured intraoperatively was 71%
      sensitive and 86% specific, whereas a greater than 75% decline in rPTH level in
      the PACU was 100% sensitive and 88% specific for predicting symptomatic
      hypocalcemia. CONCLUSIONS: The rPTH assay is a highly accurate and effective tool
      for predicting symptomatic hypocalcemia immediately after thyroidectomy. Routine
      utilization of this assay is recommended, because it will allow safe and timely
      discharge of normocalcemic patients and the early identification of patients
      requiring treatment of postthyroidectomy hypocalcemia.

PMID- 16571090
TI  - Action of topical thyroid hormone analogues on glucocorticoid-induced skin
      atrophy in mice.
AB  - Previously we demonstrated the stimulation of collagen synthesis in
      triiodothyroacetic acid (TRIAC)-topically treated human and mice. In the present
      study, we have evaluated the dose response effect of thyroid hormone (TH)
      analogues and tretinoin on glucocorticoid-induced skin atrophy in a haired mouse
      model. For this investigation, we treated haired mice twice daily for 7 days with
      various topically administered doses of TRIAC, triiodothyronine-sodium salt (T(3)
      Na), diiodothyroacetic acid (DIAC), 3,5-diiodothyropropionic acid (DITPA), and
      tretinoin with 0.2 mM betamethasone17-valerate (BM), or with the vehicle as a
      control group. We also investigated a combination of commercial betamethasone
      dipropionate (BD) 0.05% cream and various doses of TRIAC on mouse skin. TRIAC was
      able to reverse the skin atrophy by 25% in a daily dose of 1 nmol/cm(2) in the
      presence of 0.2 mM BM (p < 0.05). Neither other TH analogues nor TRIAC in lower
      and higher concentrations had a significant inhibitory effect on dermal atrophy
      (p > 0.05). A combination of 0.2 mM BM and 10 nmol/cm(2) TRIAC was able to
      prevent dermal atrophy by 18%. The addition of TRIAC to 0.05% BD cream in a final
      concentration of 0.1% was able partially to reverse the dermal atrophy by 15% (p
      < 0.05). TRIAC alone in a concentration of 1,000 nmol/cm(2) stimulated dermal
      proliferation by 34% (p < 0.05). Other TH analogues alone had no stimulatory
      effect on dermal proliferation. Tretinoin 0.8 mM was able to inhibit dermal
      atrophy by 20% (p < 0.05) and had an effect on dermal thickness of 85% (p <
      0.05). However, severe side effects with edema, erythema, and scaling were
      commonly observed in all tretinoin-treated mouse skin, which could partly explain
      the increase in dermal thickness. In contrast, no skin side effects were observed
      after treatment with TRIAC. This study indicates that TRIAC may have a
      therapeutic effect on BM-induced dermal atrophy in mouse skin and a direct
      stimulatory effect on dermal proliferation when given alone.

PMID- 16571091
TI  - Incidence of postradioiodine immunogenic hyperthyroidism/Graves' disease in
      relation to a temporary increase in thyrotropin receptor antibodies after
      radioiodine therapy for autonomous thyroid disease.
AB  - BACKGROUND: The aim of the study was to analyze retrospectively the incidence of
      postradioiodine immunogenic hyperthyroidism/Graves' disease in relation to a
      temporary increase in TSH-receptor antibodies without overt hyperthyroidism after
      radioiodine therapy for autonomous thyroid disease. PATIENTS AND METHODS: Between
      May 2000 and May 2003 all patients (n = 1,357) who had undergone radioiodine
      therapy for autonomous thyroid disease were retrospectively analyzed for
      development of postradioiodine immunogenic hyperthyroidism. On pretreatment
      evaluation 565 of 1,357 patients (41.6%) had unifocal autonomous thyroid disease
      (UFA), 693 of 1,357 patients (51.1%) had multifocal autonomous thyroid disease
      (MFA), and 99 of 1,357 patients (7.3%) had diffuse thyroid disease (DISS). Free
      triiodothyronine (FT(3)), free thyroxine (FT(4)), thyrotropin (TSH), and thyroid
      antibodies were measured. Ultrasound examinations and thyroid scintigraphy were
      performed before and after radioiodine therapy. A sensitive assay with the human
      TSH receptor as antigen was chosen for measurement of the TSH receptor antibody
      and the study was limited to analysis of data obtained since introduction of this
      assay. RESULTS: Fifteen of 1,357 patients (1.1%) (UFA, 8/565 = 1.4%; MFA, 6/693 =
      0.9%; DISS 1/99 = 1.0%) developed postradioiodine hyperthyroidism between 1 and
      13 months after radioiodine therapy with clinically overt hyperthyroidism and an
      elevation of TSH receptor antibodies. Patients with elevated thyroid peroxidase
      (TPO) antibodies before radioiodine therapy had an almost 10-fold (6/57 patients
      =10.5%) higher risk of developing postradioiodine immunogenic hyperthyroidism.
      Thirteen of 999 patients (1.3%) with antibody measurements after radioiodine
      therapy (UFA, 2/421 = 0.5%; MFA, 9/494 = 1.8%, DISS, 2/84 = 2.4%) had increased
      levels of TSH receptor antibodies and, to some extent, TPO antibodies without
      development of clinically overt hyperthyroidism. CONCLUSIONS: There is an
      estimated 1.1% risk of developing postradioiodine immunogenic
      hyperthyroidism/Graves' disease in patients undergoing radioiodine therapy for
      autonomous thyroid disease and this increases approximately 10-fold when TPO
      antibody levels are elevated before radioiodine therapy. Furthermore, there is an
      estimated 1.3% risk of a temporary increase of TSH receptor antibodies after
      radioiodine therapy for autonomous thyroid disease without development of
      clinically overt hyperthyroidism.

PMID- 16571092
TI  - Natural course of autoimmune thyroiditis after elimination of iodine deficiency
      in northwestern Greece.
AB  - We have previously reported the elimination of iodine deficiency and increasing
      prevalence of autoimmune thyroiditis (AIT) among schoolchildren in northwestern
      Greece. This study followed up 29 children (12-18 years old) with AIT for 5 years
      to track its course in the postiodination era. At diagnosis, thyroid peroxidase
      autoantibodies (TPOAbs) were positive in 25 children (86%) and became positive in
      all children during follow-up. Thyroglobulin autoantibodies (TgAbs) were positive
      in 17 children at diagnosis (59%) and became positive in 3 more children (69%).
      Both antibody types increased by the end of the observation period (p < 0.005).
      Regarding thyroid function, 7 children (24%) at diagnosis had subclinical
      hypothyroidism that persisted and 4 more children developed subclinical
      hypothyroidism during the study period (38%). Only 5 of these children (45%) had
      positive TgAbs. There was an increase in thyrotropin (TSH) so that at the end of
      the study all children had TSH greater than 2.5 mU/L but none developed overt
      hypothyroidism. Thyroid hypoechogenicity that increased over time was seen in all
      children, especially in those with subclinical hypothyroidism. In conclusion,
      both antibody types increased in frequency and level, but TPOAbs were the
      predominant autoimmunity marker predictive of impending thyroid failure in
      children with AIT, as was thyroid hypoechogenicity on ultrasound.

PMID- 16571094
TI  - Contribution of routine chest x-ray in the long-term follow-up of patients with
      differentiated thyroid carcinoma.
AB  - CONTEXT: Chest x-ray (CXR) is performed routinely in patients with differentiated
      thyroid cancer (DTC) but its importance is not well defined. OBJECTIVE: Determine
      the contribution of routine CXR in the detection of intrathoracic metastases in
      patients with DTC on follow-up. DESIGN: Retrospective chart review. SETTING:
      Comprehensive cancer center. PATIENTS: PATIENTS with localized DTC, seen at the
      University of Texas M. D. Anderson Cancer Center over a 20-year period. MAIN
      OUTCOMES: CXR abnormality developed in 6.6% of patients. RESULTS: Of 333
      patients, (298 papillary and 35 follicular thyroid carcinoma), 22 patients (6.6%)
      (18 papillary and 4 follicular) developed abnormal CXR. Median interval to CXR
      conversion was 66 months (range, 8-228 months). Most had additional evidence of
      disease at the time of CXR conversion. At last follow-up, 9 were alive with
      disease, 7 had died of other etiology, and 6 had died of DTC. Of 311 patients
      with normal CXRs throughout, (280 papillary and 31 follicular) 226 had no
      evidence of disease, 71 were alive with disease, and 14 had died of other
      etiology at last follow-up. CONCLUSIONS: In the absence of other evidence of
      disease, the contribution of CXR is limited in the long-term follow-up of
      patients with DTC.

PMID- 16571093
TI  - Serum thyrotropin receptor antibodies concentrations in patients with Graves'
      disease before, at the end of methimazole treatment, and after drug withdrawal:
      evidence that the activity of thyrotropin receptor antibody and/or thyroid
      response modify during the observation period.
AB  - AIM AND METHODS: We performed a quantitative retrospective analysis of serum
      thyrotropin receptor antibody (TRAb) concentrations measured by a second
      generation radioreceptor assay in 58 patients with Graves' disease (GD) at the
      onset of the disease, at the end of 18 month methimazole (MMI) treatment, and
      after MMI withdrawal in order to evaluate the correlation between the presence of
      these antibodies and the relapse of hyperthyroidism. Sixty healthy subjects were
      enrolled as a control group. RESULTS: Before MMI treatment the best cutoff TRAb
      value for identifying patients with GD was 1.45 UI/L (specificity, 100%;
      sensitivity, 98.3%). At the end of MMI treatment, serum TRAb concentrations were
      significantly lower (p < 0.001) than those measured at baseline, but they were
      still significantly higher (p < 0.001) than those found in the control subjects.
      At the end of MMI treatment, 44 patients (75.9%) had positive TRAb values (>1.45
      UI/L). After MMI withdrawal (median, 15 months), 34 patients (58.6%) became
      hyperthyroid, 4 patients (6.9%) became hypothyroid, and 20 patients (34.5%)
      remained euthyroid. There was a significant correlation between serum TRAb
      concentrations at the end of MMI treatment and the percentage of patients who
      became hyperthyroid (r: 0.56; p < 0.001) and the time of appearance of
      hyperthyroidism (r: -0.38; p = 0.03). All 4 patients with TRAb values below 0.9
      UI/L at the end of MMI treatment remained euthyroid throughout the follow-up
      period. Among the 27 patients who had serum TRAb values higher than 4.4 UI/L, 23
      developed hyperthyroidism and 4 hypothyroidism. The TRAb values between 0.9 and
      4.4 UI/L did not discriminate between the 27 patients (46.6%) who remained
      euthyroid from those who had relapse of hyperthyroidism. Thus a different TRAb
      end of treatment cutoff was calculated to identify patients who became again
      hyperthyroid. This TRAb cutoff value was 3.85 UI/L (sensitivity, 85.3%;
      specificity, 96.5%). All but 1 patient who had serum TRAb values above 3.85 UI/L
      became hyperthyroid after MMI was withdrawn (positive predictive value, 96.7%).
      In these patients, relapse of hyperthyroidism was independent of the changes in
      serum TRAb concentrations (r: 0.27; p = 0.15) and occurred after a median period
      of 8 weeks (range, 4-48). Hyperthyroidism also developed in 5 of 24 patients who
      had serum TRAb concentrations lower than 3.85 UI/L at the end of MMI treatment.
      In these 5 patients the relapse of hyperthyroidism occurred after a median period
      of 56 weeks (range, 24-120) and was always accompanied by an increase in serum
      TRAb concentrations. CONCLUSIONS: TRAb persist in the blood of most patients with
      GD after 18 months of MMI treatment. Both the frequency and the time of
      appearance of hyperthyroidism are closely correlated with serum TRAb
      concentrations at the end of MMI treatment. Our data would suggest that TRAb
      maintain stimulating activity after a full course of MMI treatment in the large
      majority of patients with GD. However, it is likely that the potency of these
      antibodies and/or the thyroid response to them change during treatment, as
      suggested by the different values measured in euthyroid control subjects and in
      euthyroid patients after MMI treatment.

PMID- 16571095
TI  - Acute suppurative thyroiditis caused by Pasteurella multocida and associated with
      thyrotoxicosis.
AB  - Acute suppurative thyroiditis (AST) is an uncommon condition of the thyroid
      gland. Organisms of the staphylococcal and streptococcal species are the most
      commonly reported causative agents. Rarely, AST has been associated with
      transient hyperthyroidism. We report a unique case of AST that was caused by
      Pasteurella multocida and was associated with thyrotoxicosis in a previously
      healthy 51-year-old woman.

PMID- 16571096
TI  - New multiple somatic mutations in the RET proto-oncogene associated with a
      sporadic medullary thyroid carcinoma.
AB  - Medullary thyroid carcinoma (MTC) occurs mostly as a sporadic tumor or in
      connection with inherited cancer syndromes-multiple endocrine neoplasia (MEN)
      types 2A and 2B and familial MTC. Germline mutations in the RET proto-oncogene
      are found in most of the familial cases. Somatic mutations in the RET proto
      oncogene are detected in 23%-69% of patients with sporadic MTC. The most frequent
      somatic mutation is Met918Thr in exon 16 and only a small percentage of mutations
      in other RET exons have been observed. In a very few cases double mutations were
      found. Genetic screening for somatic mutations in RET exons 10, 11, 13, 14, 15,
      and 16 in Czech patients with sporadic MTC was carried out by DNA sequencing.
      This study presents a new triplesomatic mutation Gly911Asp, Met918Thr, and
      Glu921Lys in exon 16 of the RET proto-oncogene detected in an 18-year-old Czech
      male patient. In the second case, a new double-somatic mutation Val591Ile in exon
      10 with a concomitant somatic mutation Met918Thr in exon 16 was found in a 77
      year-old Czech female patient. These both newly described somatic multiple
      mutations were revealed in a hemizygous status, the loss of heterozygosity in
      tumor tissues in comparison with germline DNA was confirmed.

PMID- 16571097
TI  - It's all in the head: insomnia and anxiety caused by thyrotropin-secreting
      pituitary adenoma.

PMID- 16571098
TI  - Solitary fibrous tumor of the thyroid gland associated with papillary thyroid
      carcinoma.

PMID- 16571104
TI  - Dihydroceramide:sphinganine C-4-hydroxylation requires Des2 hydroxylase and the
      membrane form of cytochrome b5.
AB  - Des2 (degenerative spermatocyte 2) is a bifunctional enzyme that produces
      phytoceramide and ceramide from dihydroceramide. The molecular mechanism involved
      in C-4-hydroxylation has not been studied in detail. In the present paper, we
      report that C-4-hydroxylation requires an electron-transfer system that includes
      cytochrome b5 and that the hydroxylase activity is reconstituted in an in vitro
      assay with purified recombinant Des2. FLAG-tagged mouse Des2 was expressed in
      insect Sf9 cells and was purified by solubilization with digitonin and anti-FLAG
      antibody affinity column chromatography. The activity of
      dihydroceramide:sphinganine C-4-hydroxylase was reconstituted with the purified
      FLAG-Des2, mb5 (the membrane form of cytochrome b5) and bovine erythrocyte
      membrane. The apparent K(m) and V(max) of Des2 for the substrate N
      octanoylsphinganine were 35 microM and 40 nmol x h(-1) x mg of protein(-1)
      respectively. The K(m) of the hydroxylase for mb5 was 0.8 microM. Interestingly,
      mb5 was not replaced with the soluble form of cytochrome b5, which lacks the C
      terminal membrane-spanning domain. The erythrocyte membrane was separated into
      Triton X-100-soluble and -insoluble fractions, and the detergent-soluble fraction
      was replaced by the soluble or membrane form of b5R (NADH-cytochrome b5
      reductase). The Triton-X-100-insoluble fraction contained trypsin-resistant
      factors. The Des2 protein is found in the endoplasmic reticulum and is assumed to
      have three membrane-spanning domains. The findings of the present study indicate
      that the hydroxylation requires complex formation between Des2 and mb5 via their
      membrane-spanning domains and electron transfer from NADH to the substrate via
      the reduction of mb5 by b5R.

PMID- 16571106
TI  - Impact of discussion on preferences elicited in a group setting.
AB  - BACKGROUND: The completeness of preferences is assumed as one of the axioms of
      expected utility theory but has been subject to little empirical study. METHODS:
      Fifteen non-health professionals was recruited and familiarised with the standard
      gamble technique. The group then met five times over six months and preferences
      were elicited independently on 41 scenarios. After individual valuation, the
      group discussed the scenarios, following which preferences could be changed.
      Changes made were described and summary measures (mean and median) before and
      after discussion compared using paired t test and Wilcoxon Signed Rank Test. Semi
      structured telephone interviews were carried out to explore attitudes to
      discussing preferences. These were transcribed, read by two investigators and
      emergent themes described. RESULTS: Sixteen changes (3.6%) were made to
      preferences by seven (47%) of the fifteen members. The difference between
      individual preference values before and after discussion ranged from -0.025 to
      0.45. The average effect on the group mean was 0.0053. No differences before and
      after discussion were statistically significant. The group valued discussion
      highly and suggested it brought four main benefits: reassurance; improved
      procedural performance; increased group cohesion; satisfying curiosity.
      CONCLUSION: The hypothesis that preferences are incomplete cannot be rejected for
      a proportion of respondents. However, brief discussion did not result in
      substantial number of changes to preferences and these did not have significant
      impact on summary values for the group, suggesting that incompleteness, if
      present, may not have an important effect on cost-utility analyses.

PMID- 16571105
TI  - Spontaneous rescue from cystic fibrosis in a mouse model.
AB  - BACKGROUND: From the original CftrTgH(neoim)Hgu mutant mouse model with a
      divergent genetic background (129P2, C57BL/6, MF1) we have generated two inbred
      CftrTgH(neoim)Hgu mutant strains named CF/1-CftrTgH(neoim)Hgu and CF/3
      CftrTgH(neoim)Hgu, which are fertile and show normal growth and lifespan. Initial
      genome wide scan analysis with microsatellite markers indicated that the two
      inbred strains differed on the genetic level. In order to further investigate
      whether these genetic differences have an impact on the disease phenotype of
      cystic fibrosis we characterised the phenotype of the two inbred strains.
      RESULTS: Reduced amounts, compared to wild type control animals, of correctly
      spliced Cftr mRNA were detected in the nasal epithelia, lungs and the intestine
      of both inbred CftrTgH(neoim)Hgu strains, with higher residual amount observed
      for CF/1-CftrTgH(neoim)Hgu than CF/3-CftrTgH(neoim)Hgu for every investigated
      tissue. Accordingly the amounts of wild type Cftr protein in the intestine were
      9% for CF/1-CftrTgH(neoim)Hgu and 4% for CF/3-CftrTgH(neoim)Hgu. Unlike the
      apparent strain and/or tissue specific regulation of Cftr mRNA splicing, short
      circuit current measurements in the respiratory and intestinal epithelium
      revealed that both strains have ameliorated the basic defect of cystic fibrosis
      with a presentation of a normal electrophysiology in both tissues. CONCLUSION:
      Unlike the outbred CftrTgH(neoim)Hgu insertional mouse model, which displayed the
      electrophysiological defect in the gastrointestinal and respiratory tracts
      characteristic of cystic fibrosis, both inbred CftrTgH(neoim)Hgu strains have
      ameliorated the electrophysiological defect. On the basis of these findings both
      CF/1-CftrTgH(neoim)Hgu and CF/3-CftrTgH(neoim)Hgu offer an excellent model
      whereby determination of the minimal levels of protein required for the
      restoration of the basic defect of cystic fibrosis can be studied, along with the
      modulating factors which may affect this outcome.

PMID- 16571108
TI  - Female genital mutilation of a karyotypic male presenting as a female with
      delayed puberty.
AB  - BACKGROUND: Female genital mutilation (FGM) is commonly practiced mainly in a
      belt reaching from East to West Africa north of the equator. The practice is
      known across socio-economic classes and among different ethnic, religious, and
      cultural groups. Few studies have been appropriately designed to measure the
      health effects of FGM. However, the outcome of FGM on intersex individuals has
      never been discussed before. CASE PRESENTATION: The patient first presented as a
      female with delayed puberty. Hormonal analysis revealed a normal serum prolactin
      level of 215 Micro/L, a low FSH of 0.5 Micro/L, and a low LH of 1.1 Micro/L. Type
      IV FGM (Pharaonic circumcision) had been performed during childhood. Chromosomal
      analysis showed a 46, XY karyotype and ultrasonography verified a soft tissue
      structure in the position of the prostate. CONCLUSION: FGM pose a threat to the
      diagnosis and management of children with abnormal genital development in the
      Sudan and similar societies.

PMID- 16571107
TI  - Major congenital malformations and residential proximity to a regional industrial
      park including a national toxic waste site: an ecological study.
AB  - BACKGROUND: Public concern about exposure to emissions from the regional
      industrial park (IP), including 17 chemical plants and the national industrial
      toxic waste site, initiated this study of the possible association between major
      congenital malformations (MCM) and residence near the IP in Israel's Southern
      District. METHODS: The study was conducted during the period 1995-2000 and
      included 63,850 deliveries. Data on deliveries and MCM detected at births were
      obtained from the regional medical center, and stratified by ethnicity and type
      of locality. As exposure indicator we used distance categories (proximal and
      distant) and predominant wind direction from the IP. Distance stratification was
      based on the geographical distribution of the localities and complaints about the
      odor related to IP emissions. Based on these complaints, localities up to 20 km
      from the IP were considered proximal to the IP. RESULTS: Average rates of MCM
      were 5.0% and 4.1% for Bedouin and Jewish newborns, respectively. The rate of MCM
      for Bedouin from proximal localities was significantly greater compared with
      distant localities (5.6% vs. 4.8%; RR = 1.17 with 95% CI: 1.04-1.29). In the
      proximal Bedouin permanent localities, the MCM rate reached 8.2 %, which was
      significantly higher than in distant areas (RR = 1.63, 95% CI: 1.39-1.80).
      Significant risk increase of central nervous system MCM was found in these
      localities, compared to distant ones (RR = 2.27, 95% CI: 1.44-3.60). Among
      newborns from the traditional tribal settlements, proximity to the IP was
      associated with increased rates of the following MCM: 1) all combined, 2) those
      associated with chromosomal abnormalities, and 3) those defined as "others
      unclassified MCM." Comparison of autosomal recessive disease rates by proximity
      to the IP in Bedouin newborns indicates that the observed increased risk of MCM
      is not explained by consanguineous marriages. The rates of MCM in the Jewish
      population were similar among "exposed" and "unexposed" inhabitants. CONCLUSION:
      Residential proximity to the IP is associated with increased rates of MCM among
      Arab-Beduin but not in Jewish populations. These observations indicate the need
      for public health protection of a vulnerable society in transition, although the
      relative importance of chemical exposure and health care utilization requires
      further study.

PMID- 16571109
TI  - Proteins pattern alteration in AZT-treated K562 cells detected by two-dimensional
      gel electrophoresis and peptide mass fingerprinting.
AB  - In this study we report the effect of AZT on the whole protein expression profile
      both in the control and the AZT-treated K562 cells, evidenced by two-dimensional
      gel electrophoresis and peptide mass fingerprinting analysis. Two-dimensional
      gels computer digital image analysis showed two spots that appeared up-regulated
      in AZT-treated cells and one spot present only in the drug exposed samples. Upon
      extraction and analysis by peptide mass fingerprinting, the first two spots were
      identified as PDI-A3 and stathmin, while the third one was proved to be NDPK-A.
      Conversely, two protein spots were present only in the untreated K562 cells, and
      were identified as SOD1 and HSP-60, respectively.

PMID- 16571111
TI  - Uneven distribution of nucleoside transporters and intracellular enzymatic
      degradation prevent transport of intact [14C] adenosine across the sheep choroid
      plexus epithelium as a monolayer in primary culture.
AB  - BACKGROUND: Efflux transport of adenosine across the choroid plexus (CP)
      epithelium might contribute to the homeostasis of this neuromodulator in the
      extracellular fluids of the brain. The aim of this study was to explore adenosine
      transport across sheep CP epithelial cell monolayers in primary culture. METHODS:
      To explore transport of adenosine across the CP epithelium, we have developed a
      method for primary culture of the sheep choroid plexus epithelial cells (CPEC) on
      plastic permeable supports and analysed [14C] adenosine transport across this
      cellular layer, [14C] adenosine metabolism inside the cells, and cellular uptake
      of [14C] adenosine from either of the chambers. The primary cell culture
      consisted of an enriched epithelial cell fraction from the sheep fourth ventricle
      CP and was grown on laminin-precoated filter inserts. RESULTS AND CONCLUSION:
      CPEC grew as monolayers forming typical polygonal islands, reaching optical
      confluence on the third day after the seeding. Transepithelial electrical
      resistance increased over the time after seeding up to 85 +/- 9 Omega cm2 at day
      8, while permeability towards [14C] sucrose, a marker of paracellular diffusion,
      simultaneously decreased. These cells expressed some features typical of the CPEC
      in situ, including three nucleoside transporters at the transcript level that
      normally mediate adenosine transport across cellular membranes. The estimated
      permeability of these monolayers towards [14C] adenosine was low and the same
      order of magnitude as for the markers of paracellular diffusion.However,
      inhibition of the intracellular enzymes, adenosine kinase and adenosine
      deaminase, led to a significant increase in transcellular permeability,
      indicating that intracellular phosphorylation into nucleotides might be a reason
      for the low transcellular permeability. HPLC analysis with simultaneous detection
      of radioactivity revealed that [14C] radioactivity which appeared in the acceptor
      chamber after the incubation of CPEC monolayers with [14C] adenosine in the donor
      chamber was mostly present as [14C] hypoxanthine, a product of adenosine
      metabolic degradation. Therefore, it appears that CPEC in primary cultures act as
      an enzymatic barrier towards adenosine. Cellular uptake studies revealed that
      concentrative uptake of [14C] adenosine was confined only to the side of these
      cells facing the upper or apical chamber, indicating uneven distribution of
      nucleoside transporters.

PMID- 16571110
TI  - Smad7 and protein phosphatase 1alpha are critical determinants in the duration of
      TGF-beta/ALK1 signaling in endothelial cells.
AB  - BACKGROUND: In endothelial cells (EC), transforming growth factor-beta (TGF-beta)
      can bind to and transduce signals through ALK1 and ALK5. The TGF-beta/ALK5 and
      TGF-beta/ALK1 pathways have opposite effects on EC behaviour. Besides
      differential receptor binding, the duration of TGF-beta signaling is an important
      specificity determinant for signaling responses. TGF-beta/ALK1-induced Smad1/5
      phosphorylation in ECs occurs transiently. RESULTS: The temporal activation of
      TGF-beta-induced Smad1/5 phosphorylation in ECs was found to be affected by de
      novo protein synthesis, and ALK1 and Smad5 expression levels determined signal
      strength of TGF-beta/ALK1 signaling pathway. Smad7 and protein phosphatase 1alpha
      (PP1alpha) mRNA expression levels were found to be specifically upregulated by
      TGF-beta/ALK1. Ectopic expression of Smad7 or PP1alpha potently inhibited TGF
      beta/ALK1-induced Smad1/5 phosphorylation in ECs. Conversely, siRNA-mediated
      knockdown of Smad7 or PP1alpha enhanced TGF-beta/ALK1-induced signaling
      responses. PP1alpha interacted with ALK1 and this association was further
      potentiated by Smad7. Dephosphorylation of the ALK1, immunoprecipitated from cell
      lysates, was attenuated by a specific PP1 inhibitor. CONCLUSION: Our results
      suggest that upon its induction by the TGF-beta/ALK1 pathway, Smad7 may recruit
      PP1alpha to ALK1, and thereby control TGF-beta/ALK1-induced Smad1/5
      phosphorylation.

PMID- 16571112
TI  - N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a movement disorder caused by the
      degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The
      molecular basis of this neural death is unknown, but genetic predisposition and
      environmental factors may cause the disease. Sequence variations in N
      acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been
      associated with PD, but results are contradictory. METHODS: We analyzed three
      NAT2 genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E),
      which are known to result in a slow acetylator phenotype. Using validated PCR
      RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects and
      124 PD patients for these genetic variations. Further, we have undertaken a
      systematic review of NAT2 studies on PD and we incorporated our results in a meta
      analysis consisting of 10 studies, 1,206 PD patients and 1,619 control subjects.
      RESULTS: Overall, we did not find significant differences in polymorphic
      acetylation genotypes in PD and control subjects. In the meta-analysis of slow
      acetylators from 10 studies and representing 604/1206 PD vs. 732/1619 control
      subjects, a marginally significant odds ratio (OR) of 1.32 (95% CI 1.12-1.54, p <
      0.05) was obtained. Re-analysis of the data to exclude the only two studies
      showing positive association of slow acetylators to PD, resulted in a non
      significant OR (1.07, 95% CI 0.9-1.28). Furthermore, meta-analysis of studies for
      c.590G>A, where both allele and genotype frequencies in PD vs. control subjects
      were analyzed, did not give significant summary odds ratios as well. CONCLUSION:
      We found little evidence for differences in polymorphic acetylation genotypes in
      PD and control subjects. Results of the meta-analyses did not also provide
      conclusive evidence for an overall association of NAT2 slow acetylator genotypes
      to PD.

PMID- 16571113
TI  - Acute psychiatric admissions from an out-of-hours Casualty Clinic; how do
      referring doctors and admitting specialists agree?
AB  - BACKGROUND: Over the last decades there has been an increasing pressure on the
      acute psychiatric wards in Norway. The major contributor to psychiatric acute
      admissions at the University Hospital of North Norway in the city of Tromso in
      2001 was the GP-based Tromso Casualty Clinic, only open out-of-hours. We explored
      all acute psychiatric referrals from Tromso Casualty Clinic in 2001. The purpose
      of the study was to characterize the admissions and assess the agreement between
      the referring doctors and the hospital specialists according to the need for
      hospitalization, agreement on application of the law and the diagnostic
      evaluation to assess whether the admissions were appropriate. METHODS:
      Retrospective, record based, descriptive study comprising 101 psychiatric acute
      referrals from the Tromso Casualty Clinic to the psychiatric acute wards at the
      University Hospital of North Norway. RESULTS: The specialists accepted all
      referrals except one, they mostly agreed upon the diagnoses suggested by the
      referring doctors and they mostly confirmed the application of the law.Seventy
      five percent of the admissions took place during weekends, public holidays or
      nighttimes. Diagnoses of psychoses or suicidal attempts accounted for 76 % of the
      total referrals. Substance abuse was noted for 43 %, and in 22 % of all
      admissions the patients had stopped taking their psychopharmacological
      medication. The police assisted the referring doctors in one third of all
      admissions, and was the legal representative in 52 out of 59 involuntary
      admissions. Thirty percent of the admissions were first- time admissions. Thirty
      two percent of the hospital stays lasted for three days or less. Median length of
      stay was 6.5 days. CONCLUSION: The casualty clinic physicians and the hospital
      specialists mostly agreed in their evaluation of patients indicating that most of
      the admissions were appropriate. The police was more often involved in the
      involuntary admissions than intended in the law. The proportion of patients with
      substance abuse was significant. Alternative treatment strategies should be
      developed for non-psychotic patients in need of short-term stays.

PMID- 16571114
TI  - Cigarette smoke exposure facilitates allergic sensitization in mice.
AB  - BACKGROUND: Active and passive smoking are considered as risk factors for asthma
      development. The mechanisms involved are currently unexplained. OBJECTIVE: The
      aim of this study was to determine if cigarette smoke exposure could facilitate
      primary allergic sensitization. METHODS: BALB/c mice were exposed to aerosolized
      ovalbumin (OVA) combined with air or tobacco smoke (4 exposures/day) daily for
      three weeks. Serology, lung cytopathology, cytokine profiles in bronchoalveolar
      lavage fluid (BALF) and on mediastinal lymph node cultures as well as lung
      function tests were performed after the last exposure. The natural history and
      the immune memory of allergic sensitization were studied with in vivo recall
      experiments. RESULTS: Exposure to OVA induced a small increase in OVA-specific
      serum IgE as compared with exposure to PBS (P < 0.05), while no inflammatory
      reaction was observed in the airways. Exposure to cigarette smoke did not induce
      IgE, but was characterized by a small but significant neutrophilic inflammatory
      reaction. Combining OVA with cigarette smoke not only induced a significant
      increase in OVA-specific IgE but also a distinct eosinophil and goblet cell
      enriched airway inflammation albeit that airway hyperresponsiveness was not
      evidenced. FACS analysis showed in these mice increases in dendritic cells (DC)
      and CD4+ T-lymphocytes along with a marked increase in IL-5 measured in the
      supernatant of lymph node cell cultures. Immune memory experiments evidenced the
      transient nature of these phenomena. CONCLUSION: In this study we show that
      mainstream cigarette smoke temporary disrupts the normal lung homeostatic
      tolerance to innocuous inhaled allergens, thereby inducing primary allergic
      sensitization. This is characterized not only by the development of persistent
      IgE, but also by the emergence of an eosinophil rich pulmonary inflammatory
      reaction.

PMID- 16571115
TI  - Arthritis in adults with community-acquired bacterial meningitis: a prospective
      cohort study.
AB  - BACKGROUND: Although the coexistence of bacterial meningitis and arthritis has
      been noted in several studies, it remains unclear how often both conditions occur
      simultaneously. METHODS: We evaluated the presence of arthritis in a prospective
      nationwide cohort of 696 episodes of community-acquired bacterial meningitis,
      confirmed by culture of cerebrospinal fluid, which occurred in patients aged >16
      years. The diagnosis of arthritis was based upon the judgment of the treating
      physician. To identify differences between groups Fisher exact statistics and the
      Mann-Whitney U test were used. RESULTS: Arthritis was recorded in 48 of 696 (7%)
      episodes of community-acquired bacterial meningitis in adults. Joint-fluid
      aspirations were performed in 23 of 48 patients (48%) and joint-fluid cultures
      yielded bacteria in 6 of 23 patients (26%). Arthritis occurred most frequently in
      patients with meningococcal meningitis (12%). Of the 48 patients with bacterial
      meningitis and coexisting arthritis, four died (8%) and 10 (23%) had residual
      joint symptoms. CONCLUSION: Arthritis is a common manifestation in patients with
      community-acquired bacterial meningitis. Functional outcome of arthritis in
      bacterial meningitis is generally good because meningococcal arthritis is usually
      immune-mediated, and pneumococcal arthritis is generally less deforming than
      staphylococcal arthritis. Nevertheless, additional therapeutic measures should be
      considered if clinical course is complicated by arthritis. In patients with
      infectious arthritis prolonged antibiotic therapy is mandatory.

PMID- 16571118
TI  - Systemic inflammatory response in erderly patients following hernioplastical
      operation.
AB  - The number of old and oldest old patients undergoing surgery of varying severity
      is increasing. Ageing is a process that changes the performances of most
      physiological systems and increases susceptibility to diseases and death;
      accordingly, host responses to surgical stress are altered with ageing and the
      occurrence of age-related increase in susceptibility to post-operative
      complications has been claimed. Twenty-four male patients undergoing Lichtenstein
      (LH) hernioplasty for unilateral inguinal hernia were included in this study and
      divided in two groups (Young and Old respectively), according to their age. As
      expression of the acute phase response, we measured changes in concentration of
      pro-inflammatory cytokines Tumor necrosis factor-alpha and Interleukin-1beta,
      leukocytes, acute phase proteins C-reactive protein and alpha 1-antitrypsin.
      Elderly humans showed prolonged and strong inflammatory activity compared to
      younger subjects in response to surgical stress, indicating that the acute-phase
      response to surgical stress of elderly humans varies from that of the young,
      showing initial hyperactivity and a delayed termination of the response. Thus,
      the acute phase response to surgical stress is higher in old subjects, but the
      clinical significance of this remains unclear. It is not known whether a causal
      relationship exists between this stronger acute phase response and the increases
      in susceptibility to post-operative complications observed in aged patients.

PMID- 16571116
TI  - Changes in ion transport in inflammatory disease.
AB  - Ion transport is essential for maintenance of transmembranous and transcellular
      electric potential, fluid transport and cellular volume. Disturbance of ion
      transport has been associated with cellular dysfunction, intra and extracellular
      edema and abnormalities of epithelial surface liquid volume. There is increasing
      evidence that conditions characterized by an intense local or systemic
      inflammatory response are associated with abnormal ion transport. This abnormal
      ion transport has been involved in the pathogenesis of conditions like
      hypovolemia due to fluid losses, hyponatremia and hypokalemia in diarrhoeal
      diseases, electrolyte abnormalities in pyelonephritis of early infancy,
      septicemia induced pulmonary edema, and in hypersecretion and edema induced by
      inflammatory reactions of the mucosa of the upper respiratory tract. Components
      of membranous ion transport systems, which have been shown to undergo a change in
      function during an inflammatory response include the sodium potassium ATPase, the
      epithelial sodium channel, the Cystic Fibrosis Transmembrane Conductance
      Regulator and calcium activated chloride channels and the sodium potassium
      chloride co-transporter. Inflammatory mediators, which influence ion transport
      are tumor necrosis factor, gamma interferon, interleukins, transforming growth
      factor, leukotrienes and bradykinin. They trigger the release of specific
      messengers like prostaglandins, nitric oxide and histamine which alter ion
      transport system function through specific receptors, intracellular second
      messengers and protein kinases. This review summarizes data on in vivo
      measurements of changes in ion transport in acute inflammatory conditions and in
      vitro studies, which have explored the underlying mechanisms. Potential
      interventions directed at a correction of the observed abnormalities are
      discussed.

PMID- 16571117
TI  - Inhibition of cytokine gene expression and induction of chemokine genes in non
      lymphatic cells infected with SARS coronavirus.
AB  - BACKGROUND: SARS coronavirus (SARS-CoV) is the etiologic agent of the severe
      acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic
      origin, and the cytokine profile of those cells can determine the course of
      disease. Here, we investigated the cytokine response of two human non-lymphatic
      cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV. RESULTS:
      A comparison with established cytokine-inducing viruses revealed that SARS-CoV
      only weakly triggered a cytokine response. In particular, SARS-CoV did not
      activate significant transcription of the interferons IFN-alpha, IFN-beta, IFN
      lambda1, IFN-lambda2/3, as well as of the interferon-induced antiviral genes
      ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly,
      however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon
      carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293.
      CONCLUSION: Our data indicate that SARS-CoV suppresses the antiviral cytokine
      system of non-immune cells to a large extent, thus buying time for dissemination
      in the host. However, synthesis of IP-10 and IL-8, which are established markers
      for acute-stage SARS, escapes the virus-induced silencing at least in some cell
      types. Therefore, the progressive infiltration of immune cells into the infected
      lungs observed in SARS patients could be due to the production of these
      chemokines by the infected tissue cells.

PMID- 16571119
TI  - Characteristics and prevalence of hardcore smokers attending UK general
      practitioners.
AB  - BACKGROUND: Smoking remains a public health problem and although unsolicited GPs'
      advice against smoking causes between one and three percent of smokers to stop, a
      significant proportion of smokers are particularly resistant to the notion of
      stopping smoking. These resistant smokers have been called "hardcore smokers" and
      although 16% of smokers in the community are hardcore, little is known about
      hardcore smokers presenting to primary care physicians. Consequently, this study
      reports the characteristics and prevalence of hardcore smokers attending UK GPs.
      METHODS: A cross-sectional survey using data from two different research projects
      was conducted. Data for this analysis had been collected from surgery
      consultation sessions with 73 GPs in Leicestershire, England, (42 GPs from one
      project). Research assistants distributed pre-consultation questionnaires to 4147
      adults attending GPs' surgery sessions. Questionnaires identified regular
      smokers, the proportion of hardcore smokers and their characteristics. Non
      hardcore and hardcore smokers' ages, gender and nicotine addiction levels were
      compared. RESULTS: 1170 regular smokers attended surgery sessions and, 16.1% (95%
      CI, 14.1 to 18.4) were hardcore smokers. Hardcore smokers had higher levels of
      nicotine addiction than others (p = 0.000), measured by the Heaviness of Smoking
      Index and were more likely to be male [50.5% hardcore versus 35.3% non-hardcore,
      (OR = 1.88, 95% CI = 1.4 to 2.6)] but no age differences were observed between
      groups. CONCLUSION: A significant minority of the smokers who present in general
      practice are resistant to the notion of smoking cessation and these smokers are
      more heavily nicotine addicted than others. Although clinical guidelines suggest
      that GPs should regularly advise all smokers against smoking, it is probable that
      hardcore smokers do not respond positively to this and help to make up the 97%
      99% of smokers who do not quit after being advised to stop smoking by GPs.
      General practitioners need to find approaches for raising the issue of smoking
      during consultations in ways that do not reinforce the negative opinions of
      hardcore smokers concerning smoking cessation.

PMID- 16571120
TI  - Tissue fibrocytes in patients with mild asthma: a possible link to thickness of
      reticular basement membrane?
AB  - BACKGROUND: Myofibroblasts, proposed as being derived from circulating
      fibrocytes, are considered to be important cells in thickening of the basement
      membrane in patients with asthma. We have studied the correlation of tissue
      fibrocyte levels to basement membrane thickness and the presence of fibrocytes in
      bronchoalveolar lavage fluid (BALF) in steroid-naive patients with mild asthma
      and controls. METHODS: Patients with mild asthma (n = 9) were recruited and
      divided into two categories based on whether or not fibroblast-like cells could
      be established from BALF. Non-asthmatic healthy subjects (n = 5) were used as
      controls. Colocalization of the fibrocyte markers CD34, CD45RO, procollagen I,
      and alpha-smooth muscle actin (alpha-SMA) were identified in bronchial biopsies
      from patients and controls by confocal microscopy. Kruskall-Wallis method was
      used to calculate statistical significance and Spearman coefficient of rank
      correlation was used to assess the degree of association. RESULTS: In patients
      with BALF fibroblasts, a 14-fold increase of tissue cells expressing
      CD34/CD45RO/alpha-SMA and a 16-fold increase of tissue cells expressing
      CD34/procollagen I was observed when compared to controls (p < 0.05). In
      contrast, patients without BALF fibroblasts displayed a 2-fold increase when
      compared to controls (p < 0.05). Fibrocytes were localized close to the basement
      membrane which was significantly thicker in patients with BALF fibroblasts when
      compared to the other two groups of subjects. Furthermore, basement membrane
      thickness could be correlated to the number of fibrocytes in tissue (r = 0.711).
      Fibroblasts-like cells were cultured from BALF where 17.6% of these cells
      expressed CD34, CD45RO and alpha-SMA. CONCLUSION: These findings indicate a
      correlation between recruited fibrocytes in tissue and thickness of basement
      membrane. Fibroblast progenitor cells may therefore be important in airway
      remodeling in steroid-naive patients with mild asthma.

PMID- 16571121
TI  - Geography, private costs and uptake of screening for abdominal aortic aneurysm in
      a remote rural area.
AB  - BACKGROUND: The relationship between geographical location, private costs, health
      provider costs and uptake of health screening is unclear. This paper examines
      these relationships in a screening programme for abdominal aortic aneurysm in the
      Highlands and Western Isles of Scotland, a rural and remote area of over 10,000
      square miles. METHODS: Men aged 65-74 (n = 9323) were invited to attend screening
      at 51 locations in 50 settlements. Effects of geography, deprivation and age on
      uptake were examined. Among 8,355 attendees, 8,292 completed a questionnaire
      detailing mode of travel and costs incurred, time travelled, whether accompanied,
      whether dependants were cared for, and what they would have been doing if not
      attending screening, thus allowing private costs to be calculated. Health
      provider (NHS) costs were also determined. Data were analysed by deprivation
      categories, using the Scottish Indices of Deprivation (2003), and by settlement
      type ranging from urban to very remote rural. RESULTS: Uptake of screening was
      high in all settlement types (mean 89.6%, range 87.4-92.6%). Non-attendees were
      more deprived in terms of income, employment, education and health but there was
      no significant difference between non-attendees and attendees in terms of
      geographical access to services. Age was similar in both groups. The highest
      private costs (median 7.29 pound sterling per man) and NHS screening costs (18.27
      pound sterling per man invited) were observed in very remote rural areas.
      Corresponding values for all subjects were: private cost 4.34 pound sterling and
      NHS cost 15.72 pound sterling per man invited. CONCLUSION: Uptake of screening
      for abdominal aortic aneurysm in is remote and rural setting was high in
      comparison with previous studies, and this applied across all settlement types.
      Geographical location did not affect uptake, most likely due to the outreach
      approach adopted. Private and NHS costs were highest in very remote settings but
      still compared favourably with other published studies.

PMID- 16571123
TI  - Prognostic utility of sestamibi lung uptake does not require adjustment for
      stress-related variables: a retrospective cohort study.
AB  - BACKGROUND: Increased 99mTc-sestamibi stress lung-to-heart ratio (sLHR) has been
      shown to predict cardiac outcomes similar to pulmonary uptake of thallium. Peak
      heart rate and use of pharmacologic stress affect the interpretation of lung
      thallium uptake. The current study was performed to determine whether 99mTc
      sestamibi sLHR measurements are affected by stress-related variables, and whether
      this in turn affects prognostic utility. METHODS: sLHR was determined in 718
      patients undergoing 99mTc-sestamibi SPECT stress imaging. sLHR was assessed in
      relation to demographics, hemodynamic variables and outcomes (mean follow up 5.6
      +/- 1.1 years). RESULTS: Mean sLHR was slightly greater in males than in females
      (P < 0.01) and also showed a weak negative correlation with age (P < 0.01) and
      systolic blood pressure (P < 0.01), but was unrelated to stress method or heart
      rate at the time of injection. In patients undergoing treadmill exercise, sLHR
      was also positively correlated with peak workload (P < 0.05) but inversely with
      double product (P < 0.05). The combined explanatory effect of sex, age and
      hemodynamic variables on sLHR was less than 10%. The risk of acute myocardial
      infarction (AMI) or death increased by a factor of 1.7-1.8 for each SD increase
      in unadjusted sLHR, and was unaffected by adjustment for sex, age and hemodynamic
      variables (hazard ratios 1.6-1.7). The area under the ROC curve for the
      unadjusted sLHR was 0.65 (95% CI 0.59-0.71, P < 0.0001) and was unchanged for the
      adjusted sLHR (0.65, 95% CI 0.61-0.72, P < 0.0001). CONCLUSION: Stress-related
      variables have only a weak effect on measured sLHR. Unadjusted and adjusted sLHR
      provide equivalent prognostic information for prediction of AMI or death.

PMID- 16571122
TI  - A systematic review of the health, social and financial impacts of welfare rights
      advice delivered in healthcare settings.
AB  - BACKGROUND: Socio-economic variations in health, including variations in health
      according to wealth and income, have been widely reported. A potential method of
      improving the health of the most deprived groups is to increase their income.
      State funded welfare programmes of financial benefits and benefits in kind are
      common in developed countries. However, there is evidence of widespread under
      claiming of welfare benefits by those eligible for them. One method of exploring
      the health effects of income supplementation is, therefore, to measure the health
      effects of welfare benefit maximisation programmes. We conducted a systematic
      review of the health, social and financial impacts of welfare rights advice
      delivered in healthcare settings. METHODS: Published and unpublished literature
      was accessed through searches of electronic databases, websites and an internet
      search engine; hand searches of journals; suggestions from experts; and reference
      lists of relevant publications. Data on the intervention delivered, evaluation
      performed, and outcome data on health, social and economic measures were
      abstracted and assessed by pairs of independent reviewers. Results are reported
      in narrative form. RESULTS: 55 studies were included in the review. Only seven
      studies included a comparison or control group. There was evidence that welfare
      rights advice delivered in healthcare settings results in financial benefits.
      There was little evidence that the advice resulted in measurable health or social
      benefits. This is primarily due to lack of good quality evidence, rather than
      evidence of an absence of effect. CONCLUSION: There are good theoretical reasons
      why income supplementation should improve health, but currently little evidence
      of adequate robustness and quality to indicate that the impact goes beyond
      increasing income.

PMID- 16571125
TI  - Detection of human and rodent 5-HT3B receptor subunits by anti-peptide polyclonal
      antibodies.
AB  - BACKGROUND: The 5-HT3 receptor is a member of a neurotransmitter-gated ion
      channel family which includes nicotinic acetylcholine, GABAA, and glycine
      receptors. While antibodies specific for the 5-HT3A receptor subunit are
      plentiful, and have revealed a wealth of structural and functional information,
      few antisera exist for the detection of 5-HT3B receptor subunits. Here we
      describe the generation and characterisation of a rabbit polyclonal antiserum
      that specifically recognises 5-HT3B receptor subunits RESULTS: Immunization of a
      rabbit with a 20-mer peptide, corresponding to the N-terminus of the human 5-HT3B
      receptor subunit, generated serum with polyclonal antibodies from which an IgG
      fraction was purified, yielding pAb77. The antibodies were shown to label 5-HT3B
      receptor subunits in transfected human embryonic kidney cells and rodent tissues
      using Western blots. Immunocytochemistry using pAb77 on these cells showed that 5
      HT3B receptor subunits do not reach the plasma membrane in the absence of 5-HT3A
      receptor subunits. Immunohistochemical analysis of rat brain sections showed
      pAb77 immunoreactivity in distinct populations of cells in the hippocampus.
      CONCLUSION: We have demonstrated that pAb77 antibodies specifically label native
      and recombinant 5-HT3B receptor subunits with high affinity and specificity. The
      antibody was shown to be useful for the determination of both receptor
      trafficking and also mapping 5-HT3B receptor subunit expression in the CNS.

PMID- 16571124
TI  - Expression of S100A8 correlates with inflammatory lung disease in congenic mice
      deficient of the cystic fibrosis transmembrane conductance regulator.
AB  - BACKGROUND: Lung disease in cystic fibrosis (CF) patients is dominated by chronic
      inflammation with an early and inappropriate influx of neutrophils causing airway
      destruction. Congenic C57BL/6 CF mice develop lung inflammatory disease similar
      to that of patients. In contrast, lungs of congenic BALB/c CF mice remain
      unaffected. The basis of the neutrophil influx to the airways of CF patients and
      C57BL/6 mice, and its precipitating factor(s) (spontaneous or infection induced)
      remains unclear. METHODS: The lungs of 20-day old congenic C57BL/6 (before any
      overt signs of inflammation) and BALB/c CF mouse lines maintained in sterile
      environments were investigated for distinctions in the neutrophil chemokines
      S100A8 and S100A9 by quantitative RT-PCR and RNA in situ hybridization, that were
      then correlated to neutrophil numbers. RESULTS: The lungs of C57BL/6 CF mice had
      spontaneous and significant elevation of both neutrophil chemokines S100A8 and
      S100A9 and a corresponding increase in neutrophils, in the absence of detectable
      pathogens. In contrast, BALB/c CF mouse lungs maintained under identical
      conditions, had similar elevations of S100A9 expression and resident neutrophil
      numbers, but diverged in having normal levels of S100A8. CONCLUSION: The results
      indicate early and spontaneous lung inflammation in CF mice, whose progression
      corresponds to increased expression of both S100A8 and S100A9, but not S100A9
      alone. Moreover, since both C57BL/6 and BALB/c CF lungs were maintained under
      identical conditions and had similar elevations in S100A9 and neutrophils, the
      higher S100A8 expression in the former (or suppression in latter) is a result of
      secondary genetic influences rather than environment or differential infection.

PMID- 16571126
TI  - Female smokers beyond the perimenopausal period are at increased risk of chronic
      obstructive pulmonary disease: a systematic review and meta-analysis.
AB  - BACKGROUND: Recent reports indicate that over the next decade rates of chronic
      obstructive pulmonary disease (COPD) in women will exceed those in men in the
      western world, though in most jurisdictions, women continue to smoke less
      compared with men. Whether female adult smokers are biologically more susceptible
      to COPD is unknown. This study reviewed the available evidence to determine
      whether female adult smokers have a faster decline in forced expiratory volume in
      one second (FEV1) compared with male adult smokers and whether age modifies the
      relationship between cigarette smoke and lung function decline. METHODS: A
      systematic review and a meta-analysis was performed of population-based cohort
      studies that had a follow-up period of at least 3 years, measured FEV1 on at
      least two different time points, and presented FEV1 data stratified by gender and
      smoking status in adults. RESULTS: Of the 646 potentially relevant articles, 11
      studies met these criteria and were included in the analyses (N = 55,709
      participants). There was heterogeneity in gender-related results across the
      studies. However, on average current smokers had a faster annual decline rate in
      FEV1% predicted compared with never and former smokers. Female current smokers
      had with increasing age a significantly faster annual decline in FEV1% predicted
      than male current smokers (linear regression analysis, R2 = 0.56; p = 0.008). Age
      did not materially affect the rate of decline in FEV1% predicted in male and
      female former and never smokers (p = 0.775 and p = 0.326, respectively).
      CONCLUSION: As female smokers age, they appear to experience an accelerated
      decline in FEV1% predicted compared with male smokers. Future research powered
      specifically on gender-related changes in lung function is needed to confirm
      these early findings.

PMID- 16571127
TI  - An analysis of clinical process measures for acute healthcare delivery in
      Appalachia: the Roane Medical Center experience.
AB  - OBJECTIVE: To survey management of selected emergency healthcare needs in a
      Tennessee community hospital. MATERIALS AND METHODS: In this descriptive report,
      discharges and associated standard process measures were retrospectively studied
      for Roane Medical Center (RMC) in Harriman, Tennessee (pop. 6,757). Hospital data
      were extracted from a nationwide database of short-term acute care hospitals to
      measure 16 quality performance measures in myocardial infarction (MI), heart
      failure, and pneumonia during the 14 month interval ending March 2005. The data
      also permitted comparisons with state and national reference groups. RESULTS: Of
      RMC patients with myocardial infarction (MI), 94% received aspirin on arrival, a
      figure higher than both state (85%) and national (91%) averages. Assessment of
      left ventricular dysfunction among heart failure patients was also higher at RMC
      (98%) than the state (74%) or national (79%) average. For RMC pneumonia patients,
      79% received antibiotics within 4 h of admission, which compared favorably with
      State (76%) and national (75%) average. RMC scored higher on 13 of 16 clinical
      process measures (p<0.01, sign test analysis, >95% CI) compared to state and
      national averages. DISCUSSION: Although acute health care needs are often met
      with limited resources in medically underserved regions, RMC performed above
      state and national average for most process measures assessed in this review. Our
      data were derived from one facility and the associated findings may not be
      applicable in other healthcare settings. Further studies are planned to track
      other parameters and specific clinical outcomes at RMC, as well as to identify
      specific institutional policies that facilitate attainment of target quality
      measures.

PMID- 16571128
TI  - An examination of knowledge, attitudes and practices related to lead exposure in
      South Western Nigeria.
AB  - BACKGROUND: Lead is a highly toxic and pervasive metal. Chronic exposure to low
      levels is responsible for significant health effects, particularly in children.
      Prevention remains the best option for reducing childhood lead exposure, however
      the knowledge, attitudes and practices to lead exposure in many developing
      countries is not known. METHODS: We conducted four focus group discussions (FGD)
      to evaluate knowledge attitudes and practices to lead exposure in Nigeria. An FGD
      guide was developed from the literature and preliminary discussion with members
      of the public. Participants in the FGD were randomly selected from adults living
      in Ibadan, South Western Nigeria in 2004. RESULTS: We found that there was
      limited awareness of the sources of lead exposure in the domestic environment and
      participants had little knowledge of the health effects of chronic low-dose lead
      exposure. CONCLUSION: We conclude that the findings of this study should be used,
      in conjunction with others, to develop appropriate health education intervention
      for lead exposure in the domestic environment.

PMID- 16571129
TI  - A pilot, prospective evaluation of a novel alternative for maintenance therapy of
      breast cancer-associated lymphedema [ISRCTN76522412].
AB  - BACKGROUND: Prospective investigations of complete decongestive lymphatic
      physiotherapy (CDPT), including manual lymphatic drainage (MLD), have validated
      the efficacy of these interventions for the initial reduction of edema and long
      term maintenance of limb volume in lymphedema. However, CDPT demands substantial
      time and effort from patients to maintain these benefits; the treatments are not
      always well-accepted, and patients may suffer from a deterioration in quality-of
      life or a time-dependent loss of initial treatment benefits. A new device
      designed for home use by the patient, the Flexitouch, has been developed to
      mechanically simulate MLD. We have undertaken a prospective, randomized,
      crossover study of the efficacy of the Flexitouch, when compared to massage, in
      the self-administered maintenance therapy of lymphedema. METHODS: A prospective,
      randomized, crossover study of maintenance therapy was performed in 10 patients
      with unilateral breast cancer-associated lymphedema of the arm. Each observation
      phase included self-administered treatment with the Flexitouch or massage, 1 hour
      daily for 14 days, respectively, followed by crossover to the alternate treatment
      phase. Each treatment phase was preceded by a 1 week treatment washout, with use
      of garment only. The sequence of treatment was randomly assigned. The potential
      impact of treatment modality on quality of life was assessed with serial
      administration of the SF-36. RESULTS: Statistical analysis disclosed that the
      order of treatment had no outcome influence, permitting 10 comparisons within
      each treatment group. Post-treatment arm volume reduced significantly after the
      Flexitouch, but not after self-administered massage. The patients' mean weight
      decreased significantly with Flexitouch use, but not with massage. The Flexitouch
      device was apparently well-tolerated and accepted by patients. Serial SF-36
      administration showed no deterioration in physical or psychosocial scores
      compared to baseline measurements; there were no statistical differences in
      scores when the two treatment modalities were compared. CONCLUSION: This short
      term prospective evaluation of the Flexitouch suggests that the device may
      provide better maintenance edema control than self-adiminstered massage in breast
      cancer-associated lymphedema. The apparent ease of use and reliability of
      response to the device suggest that further broad-scale testing is warranted.

PMID- 16571130
TI  - Identifying metabolic enzymes with multiple types of association evidence.
AB  - BACKGROUND: Existing large-scale metabolic models of sequenced organisms commonly
      include enzymatic functions which can not be attributed to any gene in that
      organism. Existing computational strategies for identifying such missing genes
      rely primarily on sequence homology to known enzyme-encoding genes. RESULTS: We
      present a novel method for identifying genes encoding for a specific metabolic
      function based on a local structure of metabolic network and multiple types of
      functional association evidence, including clustering of genes on the chromosome,
      similarity of phylogenetic profiles, gene expression, protein fusion events and
      others. Using E. coli and S. cerevisiae metabolic networks, we illustrate
      predictive ability of each individual type of association evidence and show that
      significantly better predictions can be obtained based on the combination of all
      data. In this way our method is able to predict 60% of enzyme-encoding genes of
      E. coli metabolism within the top 10 (out of 3551) candidates for their enzymatic
      function, and as a top candidate within 43% of the cases. CONCLUSION: We
      illustrate that a combination of genome context and other functional association
      evidence is effective in predicting genes encoding metabolic enzymes. Our
      approach does not rely on direct sequence homology to known enzyme-encoding
      genes, and can be used in conjunction with traditional homology-based metabolic
      reconstruction methods. The method can also be used to target orphan metabolic
      activities.

PMID- 16571131
TI  - Human cytomegalovirus UL27 is not required for viral replication in human tissue
      implanted in SCID mice.
AB  - Inhibition of the human cytomegalovirus UL97 kinase by maribavir is thought to be
      responsible for the antiviral activity of this compound. Some mutations that
      confer resistance to maribavir map to UL97, however additional mutations that
      also confer resistance to the drug were mapped to UL27. These open reading frames
      share a low level of homology, yet the function of pUL27 remains unknown. A
      recombinant virus with a deletion in the UL27 open reading frame was reported
      previously to exhibit a slight replication deficit, but a more important function
      in vivo was hypothesized given its homology to the UL97 kinase. The potential for
      an important function in vivo was investigated by determining if these knockout
      viruses could replicate in human tissue implanted in SCID mice. None of the AD169
      derived viruses replicated well in the implanted thymus/liver tissue, and is
      consistent with previous observations, although all of the viruses replicated to
      some degree in retinal tissue implants. Replication of the parent viruses was
      observed at 7 days post inoculation, whereas no replication was detected with any
      of the recombinant viruses with deletions in UL27. By day 14, replication was
      detected in two of the three knockout viruses and in all of the viruses by day
      42. These data are consistent with minimal defects observed in cell culture, but
      are not consistent with an important role for UL27 in vivo. We conclude that UL27
      is not required for viral replication in vivo.

PMID- 16571132
TI  - "Per cell" normalization method for mRNA measurement by quantitative PCR and
      microarrays.
AB  - BACKGROUND: Transcriptome data from quantitative PCR (Q-PCR) and DNA microarrays
      are typically obtained from a fixed amount of RNA collected per sample.
      Therefore, variations in tissue cellularity and RNA yield across samples in an
      experimental series compromise accurate determination of the absolute level of
      each mRNA species per cell in any sample. Since mRNAs are copied from genomic
      DNA, the simplest way to express mRNA level would be as copy number per template
      DNA, or more practically, as copy number per cell. RESULTS: Here we report a
      method (designated the "Percellome" method) for normalizing the expression of
      mRNA values in biological samples. It provides a "per cell" readout in mRNA copy
      number and is applicable to both quantitative PCR (Q-PCR) and DNA microarray
      studies. The genomic DNA content of each sample homogenate was measured from a
      small aliquot to derive the number of cells in the sample. A cocktail of five
      external spike RNAs admixed in a dose-graded manner (dose-graded spike cocktail;
      GSC) was prepared and added to each homogenate in proportion to its DNA content.
      In this way, the spike mRNAs represented absolute copy numbers per cell in the
      sample. The signals from the five spike mRNAs were used as a dose-response
      standard curve for each sample, enabling us to convert all the signals measured
      to copy numbers per cell in an expression profile-independent manner. A series of
      samples was measured by Q-PCR and Affymetrix GeneChip microarrays using this
      Percellome method, and the results showed up to 90 % concordance. CONCLUSION:
      Percellome data can be compared directly among samples and among different
      studies, and between different platforms, without further normalization.
      Therefore, "percellome" normalization can serve as a standard method for
      exchanging and comparing data across different platforms and among different
      laboratories.

PMID- 16571134
TI  - Injury associated with methamphetamine use: a review of the literature.
AB  - This paper reviews the literature exploring issues around methamphetamine and
      injury. There was a paucity of peer reviewed quantitative research and a lack of
      large scale epidemiological studies. Further sources described cases and others
      described injury risk as part of an overall review of methamphetamine misuse.
      Thus, a number of limitations and potential biases exist within the literature.
      The main areas where associations were noted or extrapolated with methamphetamine
      use and injury were around driving and violence. Other associations with injury
      related to methamphetamine manufacture. There was also circumstantial evidence
      for third party injury (that is injury to those not specifically involved in drug
      use or drug manufacture); however, the available data are inadequate to confirm
      these associations/risks.

PMID- 16571133
TI  - Cyclooxygenase expression is not required for release of arachidonic acid from
      cells by some nonsteroidal anti-inflammatory drugs and cancer preventive agents.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be
      effective in inhibiting colorectal cancer. Cyclooxygenase activity is thought to
      mediate, in part, this cancer preventive effect. From observations made when
      cells that express cyclooxygenase activity were treated with NSAIDs and known
      cancer preventive agents, I have postulated that arachidonic acid (AA) release is
      associated with cancer prevention. In this study, the effects of NSAIDs on two
      cells that do not express cycloxygenase activity are detailed. RESULTS: NSAIDs
      and several cancer preventive agents release AA from human colon cancer cells
      (the HCT-15 cell line). The concentrations of NSAIDs required to release
      significant amounts of AA from the HCT-15 cells are greater than those required
      to inhibit the lactacystin plus 12-0-tetradecanoyl-13-acetate stimulated
      cyclooxygenase activity of rat liver cells. NSAIDs, tamoxifen and simvastatin
      were found to hemolyze erythrocyte cells which also do not express cyclooxygenase
      activity CONCLUSION: The data demonstrate that AA release is independent of
      cyclooxygenase activity and together with hemolysis suggest that intercalation of
      the plasma membrane by some NSAIDs and cancer preventive agents, e.g. tamoxifen,
      mediates this release. A mechanism by which many of these drugs affect several
      diverse biologic properties including deesterification of membrane phospholipids
      by phospholipases to release AA is presented.

PMID- 16571135
TI  - Anti-inflammatory and anti-arthritic effects of Yucca schidigera: a review.
AB  - Yucca schidigera is a medicinal plant native to Mexico. According to folk
      medicine, yucca extracts have anti-arthritic and anti-inflammatory effects. The
      plant contains several physiologically active phytochemicals. It is a rich source
      of steroidal saponins, and is used commercially as a saponin source. Saponins
      have diverse biological effects, including anti-protozoal activity. It has been
      postulated that saponins may have anti-arthritic properties by suppressing
      intestinal protozoa which may have a role in joint inflammation. Yucca is also a
      rich source of polyphenolics, including resveratrol and a number of other
      stilbenes (yuccaols A, B, C, D and E). These phenolics have anti-inflammatory
      activity. They are inhibitors of the nuclear transcription factor NFkappaB. NFkB
      stimulates synthesis of inducible nitric oxide synthase (iNOS), which causes
      formation of the inflammatory agent nitric oxide. Yucca phenolics are also anti
      oxidants and free-radical scavengers, which may aid in suppressing reactive
      oxygen species that stimulate inflammatory responses. Based on these findings,
      further studies on the anti-arthritic effects of Yucca schidigera are warranted.

PMID- 16571136
TI  - Testosterone correlates with Venezuelan equine encephalitis virus infection in
      macaques.
AB  - Here we briefly report testosterone and cytokine responses to Venezuelan equine
      encephalitis virus (VEEV) in macaques which were used as part of a larger study
      conducted by the Department of Defense to better characterize pathological
      responses to aerosolized VEEV in non-human primates. Serial samples were
      collected and analyzed for testosterone and cytokines prior to and during
      infection in 8 captive male macaques. Infected animals exhibited a febrile
      response with few significant changes in cytokine levels. Baseline testosterone
      levels were positively associated with viremia following exposure and were
      significantly higher than levels obtained during infection. Such findings suggest
      that disease-induced androgen suppression is a reasonable area for future study.
      Decreased androgen levels during physiological perturbations may function, in
      part, to prevent immunosuppression by high testosterone levels and to prevent the
      use of energetic resources for metabolically-expensive anabolic functions.

PMID- 16571137
TI  - Protein secondary structure prediction for a single-sequence using hidden semi
      Markov models.
AB  - BACKGROUND: The accuracy of protein secondary structure prediction has been
      improving steadily towards the 88% estimated theoretical limit. There are two
      types of prediction algorithms: Single-sequence prediction algorithms imply that
      information about other (homologous) proteins is not available, while algorithms
      of the second type imply that information about homologous proteins is available,
      and use it intensively. The single-sequence algorithms could make an important
      contribution to studies of proteins with no detected homologs, however the
      accuracy of protein secondary structure prediction from a single-sequence is not
      as high as when the additional evolutionary information is present. RESULTS: In
      this paper, we further refine and extend the hidden semi-Markov model (HSMM)
      initially considered in the BSPSS algorithm. We introduce an improved residue
      dependency model by considering the patterns of statistically significant amino
      acid correlation at structural segment borders. We also derive models that
      specialize on different sections of the dependency structure and incorporate them
      into HSMM. In addition, we implement an iterative training method to refine
      estimates of HSMM parameters. The three-state-per-residue accuracy and other
      accuracy measures of the new method, IPSSP, are shown to be comparable or better
      than ones for BSPSS as well as for PSIPRED, tested under the single-sequence
      condition. CONCLUSIONS: We have shown that new dependency models and training
      methods bring further improvements to single-sequence protein secondary structure
      prediction. The results are obtained under cross-validation conditions using a
      dataset with no pair of sequences having significant sequence similarity. As new
      sequences are added to the database it is possible to augment the dependency
      structure and obtain even higher accuracy. Current and future advances should
      contribute to the improvement of function prediction for orphan proteins
      inscrutable to current similarity search methods.

PMID- 16571138
TI  - Evaluation of three polymerase chain reaction tests targeting morphological
      transforming region II, UL-83 gene and glycoprotein O gene for the detection of
      human cytomegalovirus genome in clinical specimens of immunocompromised patients
      in Chennai, India.
AB  - BACKGROUND: Human Cytomegalovirus (HCMV) continues to be an important cause of
      morbidity and occasional mortality in immunocompromised patients. Polymerase
      chain reaction (PCR) is the most sensitive and commonly used method for the
      assessment of HCMV infection in the immunocompromised patients at risk from
      severe associated clinical manifestations. However, there is little consistency
      in the qualitative PCR used for different regions of HCMV genome. Therefore, the
      performance of three Qualitative PCR tests to detect HCMV genome in clinical
      specimens from immunocompromised patients was evaluated. With pp65 antigenemia
      assay as the "gold standard", nested PCR for morphological transforming region II
      (mtr II) and glycoprotein O (gO) gene and uniplex PCR for UL 83 gene were applied
      on 92 consecutive clinical specimens obtained from 74 immunocompromised patients
      with clinically suspected HCMV disease. Virus isolation was attempted on 12
      clinical specimens from six pp65 antigenemia positive patients. Based on the pp
      65 antigenemia results as "gold standard", the sensitivity, specificity, positive
      predictive value and negative predictive value for each PCR was calculated.
      RESULTS: The PCR targeting mtr II region showed a higher sensitivity (100%) and
      negative predictive value (100%) than the other two PCRs in detecting HCMV DNA
      from clinical specimens obtained from different immunocompromised patient
      population of Chennai region, India. CONCLUSION: The results suggests that the
      optimal method of detection of HCMV DNA could be achieved by PCR using primer
      sequences targeting mtr II region of genome of HCMV in Chennai region, India.

PMID- 16571139
TI  - Screening of Tanzanian medicinal plants for anti-Candida activity.
AB  - BACKGROUND: Candida albicans has become resistant to the already limited, toxic
      and expensive anti-Candida agents available in the market. These factors
      necessitate the search for new anti-fungal agents. METHODS: Sixty-three plant
      extracts, from 56 Tanzanian plant species obtained through the literature and
      interviews with traditional healers, were evaluated for anti-Candida activity.
      Aqueous methanolic extracts were screened for anti-Candida activity by
      bioautography agar overlay method, using a standard strain of Candida albicans
      (ATCC 90028). RESULTS: Twenty- seven (48%) out of the 56 plants were found to be
      active. Extracts of the root barks of Albizia anthelmintica and Balanites
      aegyptiaca, and roots of Plectranthus barbatus showed strong activity.
      CONCLUSION: The extracts that showed strong anti-Candida activity are worth of
      further investigation in order to isolate and identify the active compounds.

PMID- 16571141
TI  - AtRTPrimer: database for Arabidopsis genome-wide homogeneous and specific RT-PCR
      primer-pairs.
AB  - BACKGROUND: Primer design is a critical step in all types of RT-PCR methods to
      ensure specificity and efficiency of a target amplicon. However, most traditional
      primer design programs suggest primers on a single template of limited genetic
      complexity. To provide researchers with a sufficient number of pre-designed
      specific RT-PCR primer pairs for whole genes in Arabidopsis, we aimed to
      construct a genome-wide primer-pair database. DESCRIPTION: We considered the
      homogeneous physical and chemical properties of each primer (homogeneity) of a
      gene, non-specific binding against all other known genes (specificity), and other
      possible amplicons from its corresponding genomic DNA or similar cDNAs
      (additional information). Then, we evaluated the reliability of our database with
      selected primer pairs from 15 genes using conventional and real time RT-PCR.
      CONCLUSION: Approximately 97% of 28,952 genes investigated were finally
      registered in AtRTPrimer. Unlike other freely available primer databases for
      Arabidopsis thaliana, AtRTPrimer provides a large number of reliable primer pairs
      for each gene so that researchers can perform various types of RT-PCR experiments
      for their specific needs. Furthermore, by experimentally evaluating our database,
      we made sure that our database provides good starting primer pairs for
      Arabidopsis researchers to perform various types of RT-PCR experiments.

PMID- 16571140
TI  - Immune responses in patients with HIV infection after vaccination with
      recombinant Hepatitis B virus vaccine.
AB  - BACKGROUND: Patients with HIV infection are at risk of co-infection with HBV, as
      the routes of transmission are shared and thus immunization with HBV vaccine
      could be protective in them. The aim of the present study was to assess the
      efficacy of recombinant vaccine in treatment-naive HIV positive patients and
      healthy controls, and to dissect out differences if any, in different limbs of
      immune response. METHODS: Forty HIV positive patients and 20 HIV negative
      controls, negative for HBsAg, HBsAbs and HBcAbs were vaccinated with three doses
      of 40 microg and 20 microg of vaccine respectively. Patients were divided into
      high CD4 and low CD4 group based on CD4+ lymphocytes of 200 and < 200/mm3
      respectively. Group II consisted of healthy controls. Detection of phenotypic
      markers was done by flowcytometry. Cytokine estimation was done by sandwich
      ELISA. HBsAbs were estimated in serum by ELISA. RESULTS: After vaccination, CD4+,
      CD8+ and CD3+ cells increased significantly in all the groups. There was no
      increase in NK cell activity in patients with high CD4+ lymphocytes and only a
      marginal increase in patients with low CD4+ lymphocytes (170 to 293/mm3) whereas
      a marked increase was observed in controls (252 to 490/mm3). After vaccination,
      although an increase in memory cells was observed in HIV positive patients, yet
      HBsAb levels were significantly lower than controls (P < 0.05) indicating a
      functional defect of memory cells in HIV/AIDS patients. Basal IFN-gamma levels
      were also significantly lower in HIV/AIDS patients (P < 0.01). Although the
      levels increased after vaccination, the peak level remained lower than in
      controls. HBsAb titers were much lower in HIV positive patients compared to
      controls. (High CD4+ group: 8834 mIU/ml, low CD4+ group: 462 mIU/ml Vs. CONTROLS:
      16,906 mIU/ml). IL-4 and IL-10 were low in patients. CONCLUSION: Despite a double
      dose in patients, IL-4 and IL-10, which regulate antibody response, were also
      lower in patients, and this together with low CD4+ counts and lack of T help,
      accounted for low HBsAb levels. Vaccination in patients with CD4+ lymphocytes <
      50/mm3 was ineffective. Thus early immunization is advocated in all HIV positive
      patients at a stage when they are still capable of mounting an adequate immune
      response.

PMID- 16571142
TI  - Cerebrospinal fluid adenosine deaminase activity: a complimentary tool in the
      early diagnosis of tuberculous meningitis.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is the commonest form of
      neurotuberculosis caused by Mycobacterium tuberculosis bacilli (MTB). The
      diagnosis of TBM is often difficult. A reliable, cost-effective and rapid
      diagnostic test, which can be performed in any standard pathology laboratory,
      could be of help in the diagnosis of TBM. In the present study we measured the
      adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of TBM and non
      TBM patients. METHOD: ADA activity in CSF was determined according to a method
      based on the Berthlot reaction, which is the formation of a colored indophenol
      complex from ammonia liberated from adenosine, and quantified
      spectrophotometrically. RESULTS: The CSF ADA activity from TBM patients was
      compared with CSF ADA from non-TBM infectious meningitis patients, and from
      patients with non-infectious neurological disorders. The mean CSF ADA activity
      was found to be significantly higher in CSF of TBM patients, 14.31 +/- 3.87 (2.99
      26.94), mean +/- SD with range, than in the CSF from non-TBM infectious
      meningitis, 9.25 +/- 2.14 (4.99-13.96) and from the non-infectious neurological
      disorders group, 2.71 +/- 1.96 (0.00-7.68), P < 0.0001 for both comparisons. A
      cut-off value of 11.39 U/L/min for the TBM patients was calculated from the mean
      + SD of the non-TBM patients. The ADA test gave a sensitivity of 82% and a
      specificity of 83% for infectious TBM when this cut-off value was used.
      CONCLUSION: This study demonstrated that ADA activity in the CSF of TBM patients,
      using a cut-off value 11.39 U/L/min, can be useful for the early differential
      diagnosis of TBM. This test can be performed in any pathology laboratory where
      more sophisticated methods are not available.

PMID- 16571144
TI  - Nonlinear analysis of biomagnetic signals recorded from uterine myomas.
AB  - OBJECTIVE: To determine if there is any non-linearity in the biomagnetic
      recordings of uterine myomas and to find any differences that may be present in
      the mechanisms underlying their signal dynamics. METHODS: Twenty-four women were
      included in the study. Sixteen of them were characterised with large myomas and 8
      with small ones. Uterine artery waveform measurements were evaluated by use of
      Pulsatility Index (PI) (normal value PI<1.45). RESULTS: Applying nonlinear
      analysis to the biomagnetic signals of the uterine myomas, we observed a clear
      saturation value for the group of large ones (mean = 11.35 +/- 1.49) and no
      saturation for the small ones. CONCLUSION: The comparison of the saturation
      values in the biomagnetic recordings of large and small myomas may be a valuable
      tool in the evaluation of functional changes in their dynamic behavior.

PMID- 16571145
TI  - Control of energy balance in relation to energy intake and energy expenditure in
      animals and man: an ecological perspective.
AB  - In this paper, we consider the control of energy balance in animals and man. We
      argue that patterns of mammalian feeding have evolved to control energy balance
      in uncertain environments. It is, therefore, expected that, under sedentary
      conditions in which the diet is rich in nutrients and abundantly available,
      animals and man will overeat. This suggests that no physiological defects are
      needed to induce overweight and ultimately obesity in man. Several considerations
      arise from these observations. The time period over which energy balance is
      controlled is far longer than allowed by most experiments. Physiological models
      of energy balance control often treat excess energy intake as a defect of
      regulation; ecological models view the same behaviour as part of normal energy
      balance control in environments where resources are uncertain. We apply these
      considerations to common patterns of human and animal feeding. We believe that
      the ecological perspective gives a more accurate explanation for the
      functionality of excess fat and the need to defend nutrient balance and avoid
      gross imbalances, as well as explaining hyperphagia in the face of plenty. By
      emphasising the common features of energy balance control in different mammalian
      species, the importance of changes in behaviour to accommodate changes in the
      environment becomes apparent. This also opens up possibilities for the control of
      body weight and the treatment of obesity in man.

PMID- 16571146
TI  - Intake of high levels of vitamin A and polyunsaturated fatty acids during
      different developmental periods modifies the expression of morphogenesis genes in
      European sea bass (Dicentrarchus labrax).
AB  - The effect of the feeding period on larval development was investigated in
      European sea bass larvae by considering the expression level of some genes
      involved in morphogenesis. Larvae were fed a control diet except during three
      different periods (period A: from 8 to 13 d post-hatching (dph); period B: from
      13 to 18 dph; period C: from 18 to 23 dph) with two compound diets containing
      high levels of vitamin A or PUFA. European sea bass morphogenesis was affected by
      these two dietary nutrients during the early stages of development. The genes
      involved in morphogenesis could be modulated between 8 and 13 dph, and our
      results indicated that retinoids and fatty acids influenced two different
      molecular pathways that in turn implicated two different gene cascades, resulting
      in two different kinds of malformation. Hypervitaminosis A delayed development,
      reducing the number of vertebral segments and disturbing bone formation in the
      cephalic region. These malformations were correlated to an upregulation of
      retinoic acid receptor gamma, retinoid X receptor (RXR) alpha and bone
      morphogenetic protein (BMP)4. An excess of PUFA accelerated the osteoblast
      differentiation process through the upregulation of RXRalpha and BMP4, leading to
      a supernumerary vertebra. These results suggest that the composition of diets
      devoted to marine fish larvae has a particularly determining effect before 13 dph
      on the subsequent development of larvae and juvenile fish.

PMID- 16571143
TI  - Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema.
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by chronic
      inflammation of the airways and progressive destruction of lung parenchyma, a
      process that in most cases is initiated by cigarette smoking. Several mechanisms
      are involved in the development of the disease: influx of inflammatory cells into
      the lung (leading to chronic inflammation of the airways), imbalance between
      proteolytic and anti-proteolytic activity (resulting in the destruction of
      healthy lung tissue) and oxidative stress. Recently, an increasing number of data
      suggest a fourth important mechanism involved in the development of COPD:
      apoptosis of structural cells in the lung might possibly be an important upstream
      event in the pathogenesis of COPD. There is an increase in apoptotic alveolar
      epithelial and endothelial cells in the lungs of COPD patients. Since this is not
      counterbalanced by an increase in proliferation of these structural cells, the
      net result is destruction of lung tissue and the development of emphysema. Data
      from animal models suggest a role for Vascular Endothelial Growth Factor (VEGF)
      in the induction of apoptosis of structural cells in the lung. Other mediators of
      apoptosis, such as caspase-3 and ceramide, could be interesting targets to
      prevent apoptosis and the development of emphysema. In this review, recent data
      on the role of apoptosis in COPD from both animal models as well as from studies
      on human subjects will be discussed. The aim is to provide an up to date summary
      on the increasing knowledge on the role of apoptosis in COPD and pulmonary
      emphysema.

PMID- 16571147
TI  - Eicosapentaenoic acid and 3,10 dithia stearic acid inhibit the desaturation of
      trans-vaccenic acid into cis-9, trans-11-conjugated linoleic acid through
      different pathways in Caco-2 and T84 cells.
AB  - Stearoyl-CoA desaturase (SCD) is a key enzyme that determines the composition and
      metabolic fate of ingested fatty acids, in particular the conversion of trans
      vaccenic acid (TVA) to conjugated linoleic acid (CLA). The present study
      addressed the hypothesis that intestinal TVA absorption and biotransformation
      into CLA can be modulated by EPA and 3,10-dithia stearic acid (DSA) via altered
      SCD mRNA levels and desaturation indices (cis-9, trans-11-CLA:TVA and oleic
      acid:stearic acid ratios) in Caco-2 and T84 cells, two well-established in vitro
      models of the human intestinal epithelium. The study determined the effect of
      acute (3 h with 0.3 mm-EPA or 0.3 mm-DSA) and acute-on-chronic (1 week with 0.03
      mm-EPA or -DSA, followed by respectively, 0.3 mm-EPA or -DSA for 3 h) treatments.
      In both cell lines, acute EPA treatment did not alter SCD desaturation indices,
      whereas the acute-on-chronic treatment affected these surrogate markers of SCD
      activity. This was associated with reduced sterol regulatory-element binding
      protein-1c and SCD mRNA levels. In contrast, acute and acute-on-chronic DSA
      treatments significantly reduced SCD desaturation indices without affecting SCD
      mRNA levels in Caco-2 cells. The present study on intestinal cells shows that the
      conversion rate of TVA to c9, t11-CLA is affected by other fatty acids present in
      the diet such as EPA, confirming previous observations in hepatic and mammary
      cell models.

PMID- 16571148
TI  - Differential effects of konbu and nori seaweed dietary supplementation on liver
      glutathione status in normo- and hypercholesterolaemic growing rats.
AB  - The effects of six balanced diets for 3 weeks on dietary intake, growth, liver
      weight and fat, plasma cholesterol, total antioxidant capacity, liver glutathione
      status and antioxidant enzymes in growing male Wistar rats were studied. Ten rats
      per group were fed casein- and soyabean-based diets with or without 2.4 %
      cholesterol-raising agent. Seven percent of the diet consisted of a cellulose
      wheat starch mix (35:65; control diets), freeze-dried nori (nori diets) or konbu
      (konbu diets). The 7 % dietary supplement of seaweeds was well accepted and
      induced normal growth rates in rats. Except for food intake, total and reduced
      glutathione and total antioxidant capacity, dietary cholesterol addition
      significantly affected (at least P<0.05) all parameters studied. Alga consumption
      affected total and reduced glutathione, glutathione reductase activity, plasma
      cholesterol, and total and cholesterol-adjusted total antioxidant capacity (at
      least P<0.05). A significant cholesterol-alga interaction was found for liver
      weight, total glutathione peroxidase (GSH-Px) and the Se-dependent GSH-Px:total
      GSH-Px ratio (at least P<0.05). GSH-Px activity increased in cholesterol-fed nori
      rats mainly as Se-dependent GSH-Px, while in konbu and control groups the GSH-Px
      activity was related to increases in both non-Se-dependent and Se-dependent GSH
      Px activities. The decrease in the antioxidant status of konbu rats was related
      to the high As content of this alga, which led to a compensatory increase in
      glutathione reductase activity in these animals. In conclusion, although some
      antioxidant compounds are present in algae, other dietary compounds, such as As,
      induced poor antioxidant status in rats.

PMID- 16571149
TI  - Protein expression of pectoralis major muscle in chickens in response to dietary
      methionine status.
AB  - The present study evaluated the effect of dietary methionine on breast-meat
      accretion and protein expression in skeletal muscle of broiler chickens in vivo.
      All broilers received a common pre-test diet up to 21 d of age, and were
      subsequently fed either a methionine-deficient (MD) or -adequate (MA) diet (3.1
      v. 4.5 g/kg diet) from age 21 to 42 d. Dietary cystine levels were 3.7 v. 3.6
      g/kg diet for the MD and MA diet, respectively. Detrimental effects on carcass
      yield (P=0.004), abdominal fat percentage (P=0.001), and breast-meat weight
      (P=0.001), yield (P=0.001), and uniformity (P=0.002) were observed and validated
      in birds fed MD diets. Via tandem MS, a total of 190 individual proteins were
      identified from pectoralis major (PM) muscle tissue. From the former composite,
      peptides from three proteins were observed to be present exclusively in breast
      muscle from those chickens fed the MD diet (pyruvate kinase, myosin alkali light
      chain-1, ribosomal-protein-L-29). No proteins were observed to be uniquely
      expressed in chickens fed MA diets. Research is warranted to further explore the
      possibility of the proteins pyruate kinase, myosin alkali light chain-1, or
      ribosomal protein L-29, as potential biological indicators of differences in
      protein expression of PM of chickens in response to a dietary methionine
      deficiency.

PMID- 16571150
TI  - Gender-related response of lipid metabolism to dietary fatty acids in the
      hamster.
AB  - Gender and dietary fatty acids are involved in the regulation of lipid
      metabolism, disturbances of which can lead to pathologies such as metabolic
      syndrome or CVD. Possible interactions between these factors were investigated in
      male and female hamsters fed diets rich in either saturated fatty acids (
      "butter" diet) or in alpha-linolenic acid ( "linseed oil" diet). Gender effect
      predominated over the diet effect on cholesterol (CH) metabolism; compared to
      males, females exhibited lower concentrations of plasma total CH (-20 %,
      P<0.001), LDL-CH (-40 %, P<0.001) and HDL-CH (-16 %, P<0.001), together with
      higher LDL receptor (+40 %) and lower HDL receptor (-60 %) hepatic content.
      Triacylglycerol (TG) metabolism was affected by diet above all: compared to
      animals fed the "butter" diet, those fed the "linseed oil" diet exhibited lower
      plasma (-23 %, P=0.046) and liver TG (-20 %, P=0.026) concentration which may
      result from both an increased beta-oxidation (P<0.001), without any change in
      PPARalpha mRNA, and a decreased hepatic lipogenesis (P=0.023), without increased
      sterol response element binding protein 1c (SREBP1c) mRNA. The response to diet
      was much more pronounced in males than in females, without gender effect on the
      transcription level of PPARalpha and SREBP1c. Finally, the "linseed oil" diet
      decreased the insulin resistance index (-80 %, P<0.001) with a more marked effect
      in males, in relation to their higher hepatic PPARgamma expression (+90 %,
      P=0.012). In conclusion, in our model, the response of either TG or CH to dietary
      fatty acids is modulated differently by gender. The possible relevance of these
      interactions to dietary practice should be taken into account in man.

PMID- 16571151
TI  - Iron solubility compared with in vitro digestion-Caco-2 cell culture method for
      the assessment of iron bioavailability in a processed and unprocessed
      complementary food for Tanzanian infants (6-12 months).
AB  - The Fe solubility test is a commonly used, easy and relatively cheap in vitro
      tool for predicting Fe bioavailability in food matrices. However, the outcome of
      a recent field trial comparing the effect on Fe status of Tanzanian infants of
      processed v. unprocessed complementary foods (CF), with otherwise the same
      composition, challenged the validity of this test for predicting Fe
      bioavailability. In the solubility test, significant more soluble Fe was observed
      in processed compared with unprocessed foods (mean 18.8 (sem 0.21) v. 4.8 (sem
      0.23) %; P<0.001). However, in the field trial, no significant difference in Fe
      status was seen between processed and unprocessed CF groups after 6 months'
      follow-up. Therefore, twenty-four samples of these CF (twelve processed and
      twelve unprocessed batches) were analysed in triplicate for Fe availability using
      an in vitro digestion-Caco-2 cell culture method and results were compared with
      solubility results. Significantly more soluble Fe was presented to Caco-2 cells
      in the processed compared with unprocessed samples (mean 11.5 (sem 1.16) v. 8.5
      (sem 2.54) %; P=0.028), but proportionally less Fe was taken up by the cells
      (mean 3.0 (sem 0.40) v. 11.7 (sem 2.22) %; P=0.007). As a net result, absolute Fe
      uptake was lower (not significantly) in processed compared with unprocessed CF
      (mean 1.3 (sem 0.16) v. 3.4 (sem 0.83) nmol/mg cell protein; P=0.052). These data
      clearly demonstrate that the Fe solubility test was not a good indicator of Fe
      bioavailability in these particular food matrices. In contrast, the results of an
      in vitro Caco-2 model supported the effects observed in vivo.

PMID- 16571152
TI  - Effects of conjugated linoleic acid on linoleic and linolenic acid metabolism in
      man.
AB  - Evidence from animal studies suggests that conjugated linoleic acid (CLA)
      modulates plasma and tissue appearance of newly synthesized PUFA. The effects of
      a 1.2g (0.5 % energy) daily intake of the cis-9,trans-11 (c9,t11) isomer of CLA,
      trans-10,cis-12 (t10,c12) isomer of CLA or olive oil (placebo) on linoleic acid
      (LA) and linolenic acid (LNA) metabolism in healthy human volunteers was
      investigated. Fifteen subjects were fed an experimental diet and supplemented
      with c9,t11-CLA, t10,c12-CLA or placebo for 7 d before consuming a tracer dose of
      U-[(13)C]LA (50 mg) and U-[(13)C]LNA (50 mg). Blood samples were taken at 0, 2,
      4, 6, 8, 24, 48, 72 and 168 h and analysed using high-precision MS. No
      differences between the groups in peak plasma [(13)C]LA (10.3-11.6 % of dose),
      [(13)C]LNA (2.5-2.9 % of dose), [(13)C]arachidonic acid (0.09-0.12 % of dose),
      [(13)C]EPA (0.04-0.06 % of dose) or [(13)C]DHA (0.06-0.10 % of dose) were
      detected. Concentration v. time curves (area under the curve) also showed no
      significant differences between groups. This suggests that, in healthy human
      subjects consuming a diet with adequate intake of essential fatty acids, CLA does
      not affect metabolism of LA or LNA.

PMID- 16571153
TI  - Effects of ingestion of tomatoes, tomato juice and tomato puree on contents of
      lycopene isomers, tocopherols and ascorbic acid in human plasma as well as on
      lycopene isomer pattern.
AB  - Tomatoes are an important part of the diet. Lycopene, the predominant carotenoid
      in tomatoes, is hypothesised to mainly mediate the health benefits of tomato
      products. Anticancer activity of tomato products and lycopene has been suggested
      by numerous studies. The aim of the present study was to investigate the effect
      of ingestion of three different tomato-based foodstuffs on plasma contents of
      lycopene, tocopherols and ascorbic acid. Because isomers of lycopene may have
      different biological activities, a special interest was to look how the lycopene
      isomer pattern is changed depending on the matrix of tomato products. Following a
      2-week depletion phase volunteers ingested 12.5 mg lycopene/d for 4 weeks
      comprising tomatoes, tomato juice or tomato puree. The basal levels of lycopene
      in plasma were comparable for all groups and decreased significantly during the 2
      weeks of depletion to approximately half of the basal values. Following
      intervention, plasma lycopene concentration increased significantly. Conversely,
      supplementation did not significantly affect levels of tocopherols and ascorbic
      acid in plasma. Regarding isomers of lycopene, the (Z)-lycopene:(all-E)-lycopene
      plasma isomer ratio was significantly changed during the study for all groups. A
      remarkable enrichment of the relative contents of (5Z)-lycopene was observed
      during the depletion period, which supports the hypothesis that lycopene (Z)
      isomers are formed within the human body after ingestion of (all-E)-lycopene.
      After dietary intervention with lycopene-rich products the isomer ratios returned
      to those observed at the start of the study. Further investigations will clarify
      the process of isomerisation in more detail.

PMID- 16571154
TI  - Daily consumption of a high-phenol extra-virgin olive oil reduces oxidative DNA
      damage in postmenopausal women.
AB  - Extra-virgin olive oils (EVOO), high in phenolic compounds with antioxidant
      properties, could be partly responsible for the lower mortality and incidence of
      cancer and CVD in the Mediterranean region. The present study aims to measure
      oxidative DNA damage in healthy human subjects consuming olive oils with
      different concentrations of natural phenols. A randomised cross-over trial of
      high-phenol EVOO (high-EVOO; 592 mg total phenols/kg) v. low-phenol EVOO (low
      EVOO; 147 mg/kg) was conducted in ten postmenopausal women in Florence. Subjects
      were asked to substitute all types of fat and oils habitually consumed with the
      study oil (50 g/d) for 8 weeks in each period. Oxidative DNA damage was measured
      by the comet assay in peripheral blood lymphocytes, collected at each visit
      during the study period. Urine samples over 24 h were collected to measure the
      excretion of the olive oil phenols. The average of the four measurements of
      oxidative DNA damage during treatment with high-EVOO was 30 % lower than the
      average during the low-EVOO treatment (P=0.02). Urinary excretion of
      hydroxytyrosol and its metabolite homovanillyl alcohol were significantly
      increased in subjects consuming high-EVOO. Despite the small sample size, the
      present study showed a reduction of DNA damage by consumption of an EVOO rich in
      phenols, particularly hydroxytyrosol.

PMID- 16571155
TI  - Trans-11-18 : 1 is effectively Delta9-desaturated compared with trans-12-18 : 1
      in humans.
AB  - The aim of this human intervention study was to evaluate the Delta9-desaturation
      of trans-11-18 : 1 (trans-vaccenic acid; tVA) to cis-9,trans-11-18 : 2 (c9,t11
      conjugated linoleic acid; CLA) and of trans-12-18 : 1 (t12) to cis-9,trans-12-18
      : 2 after a short-term (7 d) and a long-term (42 d) supplementation period. The
      conversion rates of both trans-18 : 1 isomers were estimated by lipid analysis of
      serum and red blood cell membranes (RBCM). Subjects started with a 2-week
      adaptation period without supplements. During the 42 d intervention period, the
      diet of the test group was supplemented with 3 g/d of tVA and 3 g/d of t12. The
      diet of the control group was supplemented with a control oil. Serum tVA and t12
      levels in the test group increased by fivefold and ninefold after 7 d,
      respectively, and by eight- and 12-fold after 42 d, respectively, when compared
      with the adaptation period (P< or =0.002). The serum c9,t11 CLA levels increased
      by 1.7- and 2.0-fold after 7 d and 42 d, respectively (P< or =0.001). After 42 d,
      the test group's RBCM c9,t11 CLA content was elevated by 20 % (P=0.021), whereas
      in the control group it was decreased by 50 % (P=0.002). The conversion rate of
      tVA was estimated at 24 % by serum and 19 % by RBCM. No increase in c9,t12-18 : 2
      was observed in the serum and RBCM, and thus no conversion of t12 could be
      determined. In conclusion, the endogenous conversion of dietary tVA to c9,t11 CLA
      contributes approximately one quarter to the human CLA pool and should be
      considered when determining the CLA supply.

PMID- 16571156
TI  - The effect of multi-vitamin/mineral supplementation on mortality during treatment
      of pulmonary tuberculosis: a randomised two-by-two factorial trial in Mwanza,
      Tanzania.
AB  - Malnutrition is common in pulmonary tuberculosis (TB), and may impair survival.
      The objective of this study was to assess effects of multi-vitamin/mineral (MVM)
      and zinc (Zn) supplementation during TB treatment on mortality. Patients
      diagnosed with sputum-positive pulmonary TB in Mwanza, Tanzania, were randomised,
      using a two-by-two factorial design, to Zn (45 mg) or placebo, and MVM (vitamins
      A, B, C, D, E, and selenium and copper) or placebo. Survival status was
      ascertained at the end of the 8-month TB treatment and supplementation period. Of
      499 TB patients, 213 (43 %) had HIV. The mean weight gain at 7 months was 6.88 kg
      (95 % CI 6.36, 7.41). Zn and MVM combined, but neither alone (interaction,
      P=0.03), increased weight gain by 2.37 kg (95 % CI 0.91, 3.83), irrespective of
      HIV status. Survival status at 8 months was determined for 422 patients (84.6 %),
      of which fifty-two (12.3 %) had died. Among fifty-two deaths, there were no
      effects of MVM (relative risk (RR) 0.73; 95 % CI 0.43, 1.23) and Zn (RR 0.76; 95
      % CI 0.46, 1.28). However, among HIV co-infected patients, marginally significant
      effects of both MVM (RR 0.60; 95 % CI 0.34, 1.05) and Zn (RR 0.63, 95 % CI 0.37,
      1.08) were seen, and MVM and Zn combined reduced mortality (RR 0.29; 95 % CI
      0.10, 0.80; interaction ratio 0.52). In conclusion, supplementation with MVM,
      including Zn, during treatment of pulmonary TB may reduce mortality in those co
      infected with HIV. A randomised trial of the effect of the combined intervention
      used in this study should be conducted in a different setting to confirm the
      finding.

PMID- 16571157
TI  - Maternal intake of antioxidant vitamins in pregnancy in relation to maternal and
      fetal plasma levels at delivery.
AB  - The aim of the present study was to test the hypothesis that maternal intake of
      antioxidant vitamins is associated with maternal and cord plasma levels at
      delivery. Women were recruited in early pregnancy in Aberdeen Maternity Hospital
      and habitual diet during pregnancy was assessed by a food-frequency questionnaire
      mailed at 34 weeks gestation. Blood samples were taken at recruitment (n 1149)
      and maternal (n 1149) and cord blood samples (n 747) taken at delivery for
      analyses of vitamins A, C, E and beta-carotene. Maternal plasma levels of vitamin
      E and beta-carotene at delivery were significantly higher than levels in early
      pregnancy while levels of vitamins A and C were significantly lower. Positive
      correlations were observed for maternal levels of all the vitamins between early
      pregnancy and delivery. At delivery, maternal plasma concentrations of vitamins
      A, E and beta-carotene were significantly higher than cord levels, while maternal
      levels of vitamin C were significantly lower. There were significant correlations
      between maternal and cord plasma concentrations for beta-carotene and vitamin C
      but not for vitamins A or E. Maternal dietary intakes were positively correlated
      with maternal plasma levels of vitamins C, E and beta-carotene in early
      pregnancy, with maternal plasma levels of beta-carotene and vitamin C at delivery
      and with cord plasma levels of beta-carotene and vitamin C. The results from the
      present study show that, in this population, maternal diet influences cord plasma
      levels of beta-carotene and vitamin C, but not vitamins A and E.

PMID- 16571158
TI  - Microalgal docosahexaenoic acid decreases plasma triacylglycerol in
      normolipidaemic vegetarians: a randomised trial.
AB  - Triacylglycerol (TG) lowering effects of n-3 long-chain PUFA (n-3 LCPUFA) have
      been repeatedly demonstrated, but studies investigating the individual effects of
      EPA or DHA on plasma TG and lipoproteins in man are rare. The effects of a new
      DHA-rich, almost EPA-free microalgae oil (Ulkenia sp.) on plasma lipids and
      several safety parameters were investigated in a double-blind, placebo
      controlled, parallel design intervention study. Normolipidaemic vegetarians
      (eighty-seven females, twenty-seven males) consumed daily microalgae oil (0.94 g
      DHA/d) or olive oil (as placebo) for 8 weeks. DHA supplementation decreased
      plasma TG by 23 % from 1.08 (sem 0.07) to 0.83 (sem 0.04) mmol/l (P<0.001).
      Absolute TG decreases after DHA supplementation were inversely correlated to
      baseline TG concentrations (r -0.627, P<0.001). Plasma total, LDL and HDL
      cholesterol increased significantly in the DHA group, resulting in lower TG:HDL
      cholesterol and unchanged LDL:HDL and total cholesterol:HDL cholesterol ratios.
      The intake of DHA-rich microalgae oil did not result in any physiologically
      relevant changes of safety and haemostatic factors. In conclusion, DHA-rich oil
      from microalgae Ulkenia sp. was well tolerated and can be considered a suitable
      vegetarian source of n-3 LCPUFA. Although DHA supplementation improved some CHD
      risk factors (plasma TG, TG:HDL cholesterol ratio), LDL cholesterol increased.
      Therefore, the overall effects of this intervention on CHD risk deserve further
      investigation.

PMID- 16571159
TI  - Acute postprandial effect of hydrogenated fish oil, palm oil and lard on plasma
      cholesterol, triacylglycerol and non-esterified fatty acid metabolism in
      normocholesterolaemic males.
AB  - The majority of research has focused on the association between trans unsaturated
      fatty acids (TUFA) from hydrogenated vegetable oils and heart disease even though
      TUFA are also produced from hydrogenated fish oil. We compared the acute effect
      of three solid fats on postprandial cholesterol, triacylglycerol (TAG) and NEFA
      concentrations in normocholesterolaemic males. Eight healthy male volunteers
      consumed each of the three 40 g fat meals (partially hydrogenated fish oil
      (PHFO), palm oil and lard) in random order and blood samples were drawn at 2, 4,
      6 and 8 h thereafter for lipid analysis. The postprandial response in plasma TAG,
      TAG-rich lipoprotein-TAG (TRL-TAG), total cholesterol and plasma NEFA, measured
      as the area under the postprandial curve, was not significantly different between
      the three meals (P>0.05), which varied in MUFA, PUFA and TUFA content. There was
      no marked elevation of longer-chain fatty acids (C20-22, cis or trans isomers)
      into the TRL-TAG fraction following the PHFO meal even though they provided 40 %
      of the total fatty acids in the PHFO meal. The postprandial TRL-TAG response to
      PHFO was expected to be higher, as it is higher in TUFA, lower in PUFA and
      similar in saturated fatty acid composition compared with the lard and palm oil
      test meals. The absence of a higher postprandial response following ingestion of
      PHFO could be as a result of reduced absorption and increased oxidation of long
      chain fatty acids (both cis and trans isomers).

PMID- 16571160
TI  - Satiety and substrate mobilization after oral fat stimulation.
AB  - The aim of the study was to provoke cephalic and metabolic responses by oral fat
      stimulation with different high-fat meals in the postprandial state. A randomized
      parallel design was executed with three groups of subjects (twenty-six women and
      ten men; twelve subjects per group). Oral fat stimulation was achieved by the
      modified sham feeding (MSF) technique. Five hours after a high-fat breakfast, the
      subjects were given one of three test meals in random order: a high-fat lunch,
      water or the same lunch as the MSF. The main fat sources in the high-fat lunch
      and MSF were olive oil, linoleic oil and oleic oil. For 3 h after the test meal,
      blood samples were taken for analysis of metabolite, and visual analogue scales
      of appetite profile were completed. A cephalic response appeared to be achieved
      by MSF in that we observed a relative increase in insulin and glucose; this
      response lasted up until 90 min, indicating possible vagal stimulation. NEFA
      increased significantly after MSF compared with water ingestion in the case of
      olive oil (P<0.0001) and linoleic oil (P<0.05), but not with oleic oil. MSF
      provoked a significantly higher increase in triacylglycerol and glycerol levels
      compared with water ingestion in the case of linoleic oil (P<0.05). Satiety was
      significantly increased in the eating condition and in the MSF condition
      (P<0.0002, all oils) compared with water ingestion. We conclude that cephalic and
      perhaps vagal stimulation by different fats increased the concentrations of the
      metabolites and stimulated satiety, with linoleic oil showing the strongest
      response.

PMID- 16571161
TI  - Validity and reproducibility of a semi-quantitative food-frequency questionnaire
      for estimating calcium intake in Belgian preschool children.
AB  - Relative validity and reproducibility of a semi-quantitative food-frequency
      questionnaire (FFQ) for measuring preschool children's usual Ca intake were
      assessed using parents or guardians as a proxy. Estimated diet records (EDR; 3 d)
      were used as the reference method and reproducibility was measured by repeated
      FFQ administrations 5 weeks apart. From 2095 preschool children (2.5-6.5 years)
      randomly selected in Flanders (Flemish region of Belgium), 1052 returned a FFQ
      and EDR. Stringent exclusion procedures reduced the sample for validity analyses
      to 509 children. From a separate sample of 244 preschool children, 124 returned
      two FFQ, of whom sixty were included in the reproducibility analysis. Mean Ca
      intakes were 838 (sd 305) and 777 (sd 296) mg/d for EDR and FFQ respectively,
      indicating a mean difference of 60.9 (sd 294.4) mg/d (P<0.001). Pearson's
      correlation was 0.52. Cross-classification analysis of the FFQ and EDR classified
      83 % of the subjects in the same or adjacent category and 2.4 % in extreme
      quartiles. Actual values for surrogate FFQ quartiles showed a progressive
      increase in Ca intake (P<0.001). The FFQ correctly identified 77 % of the
      children consuming less Ca than the age-specific RDA (800 mg/d). Correlation
      between repeated administrations was 0.79. No significant difference between mean
      Ca intakes was established by two administrations (23.8 (sd 161.2) mg/d). Cross
      classification of repeated administrations classified 93.4 % of the subjects in
      the same or adjacent category and no subjects in extreme categories. This FFQ
      tended to underestimate preschool children's Ca intake when administered by a
      proxy. However, it demonstrated good repeatability and fairly good ability to
      classify subjects into extremes of Ca intake.

PMID- 16571162
TI  - Dietary patterns are associated with sexual maturation in Korean children.
AB  - The purpose of this study was to investigate the association between dietary
      patterns and sexual maturation among Korean children. A cross-sectional study was
      conducted in 422 boys and 365 girls aged 9-12 years living in Seoul, Korea. Three
      day food records were obtained, and pubertal stages were determined with a
      questionnaire using Tanner stages. Body fat was measured by bioelectrical
      impedance analysis, and bone mass content at the right calcaneus was measured by
      portable dual-emission X-ray absorptiometry. Exploratory factor analysis with a
      Varimax rotation was applied to identify dietary patterns using twenty-four food
      groups. Four distinct dietary patterns--"rice and Kimchi", "shellfish and
      processed meat", "pizza and drinks" and "milk and cereal"--were obtained. Twenty
      six per cent (24 % stage 2, 2 % stage 3) of boys had genital development, and 79
      % (63 % stage 2, 16 % stage 3) of girls showed breast development. In boys,
      genital development was weakly positively associated with "shellfish and
      processed meat" dietary factor scores (odds ratio 1.65, CI 0.95, 2.89, P for
      trend 0.07) after adjusting for confounders. In girls, breast development was
      significantly positively associated with the factor score of "shellfish and
      processed meat" (odds ratio 1.88, CI 1.08, 3.26, P for trend 0.05). These results
      suggest that dietary patterns were related to body composition and sexual
      maturation among the Korean children. Further investigations are needed to
      identify components of the foods consumed in high amounts in these patterns and
      how they are related to sexual maturation.

PMID- 16571163
TI  - Intake of fish and long-chain n-3 fatty acids and the risk of coronary heart
      mortality in men and women.
AB  - This prospective study investigated the relationship between the consumption of
      fish and intake of long-chain n-3 fatty acids and the risk of coronary heart
      mortality in 2775 men and 2445 women aged from 30 to 79 years who were free of
      CHD and had participated in a health examination survey from 1967 to 1972. In
      total, 335 men and 163 women died of CHD during a follow-up until the end of
      1992. A dietary history interview method provided data on habitual consumption of
      fish and other foods over the preceding year at baseline. The intakes of long
      chain n-3 fatty acids were calculated on the basis of food composition values of
      Finnish foods. Higher consumption of fish was associated with a decreased risk of
      CHD among women, whereas no significant association was seen among men. The
      relative risk between the highest and the lowest quintile for fish consumption
      was 1.00 (95 % CI 0.70, 1.43; P for trend 0.83) for men and 0.59 (95 % CI 0.36,
      0.99; P for trend 0.02) for women in analysis adjusting for age, energy intake,
      geographical area, BMI, serum cholesterol, blood pressure, smoking, occupation
      and diabetes; however, after adjustment for dietary confounders this association
      was no longer significant. The intake of n-3 fatty acids was not significantly
      associated with the risk of CHD in either men or women. In conclusion, our
      results for women are in line with the suggested protective effect of fish
      consumption against CHD but a similar association was not, however, found in men.

PMID- 16571164
TI  - Neonatal leptin treatment programmes leptin hypothalamic resistance and
      intermediary metabolic parameters in adult rats.
AB  - We previously showed that neonatal leptin treatment programmes higher body weight
      and food intake in adult rats. Here we investigate whether leptin treatment
      during lactation affects the anorectic effect of leptin on adult rats and their
      hypothalamic leptin receptors (OB-Rb) and whether those changes could have
      consequences on intermediary metabolism. When the offspring were born, pups were
      divided into two groups: the Lep group, injected daily with leptin (8 microg/100
      g body weight, subcutaneously) for the first 10 d of lactation, and the control
      group, injected daily with saline. After weaning (day 21), body weight and food
      intake were monitored until the rats were 150 d old. Food intake was higher in
      the Lep group (approximately 14 %, P<0.05) from day 133 onwards, and body weight
      was higher (approximately 10 %, P<0.05) from day 69 onwards, compared with the
      control group. At 150 d of age, the rats were tested for food intake in response
      to either leptin (0.5 mg/kg body weight intraperitoneally; groups CL and LepL) or
      saline (groups CSal and LepSal). The CL group showed a decrease in food intake,
      but no response was observed in the LepL group, suggesting leptin resistance. The
      Lep group demonstrated a decrease in OB-Rb expression (-40 %, P<0.05),
      hyperleptinaemia (+78 %, P<0.05), hyperinsulinaemia (+100 %, P<0.02),
      hypertriacylglycerolaemia (+17 %, P<0.05) and a higher protein content in the
      body (+16 %, P<0.05) without changes in fat mass and glycaemia. We conclude that
      neonatal leptin treatment programmes both hyperleptinaemia and hyperinsulinaemia
      in adulthood, which leads to leptin resistance by reducing the expression of the
      hypothalamic leptin receptor.

PMID- 16571165
TI  - n-3 PUFA fail to affect in vivo, antigen-driven CD8+T-cell proliferation in the
      spleen of naive mice.
AB  - One of the most frequently reported immunomodulatory actions of n-3 PUFA is their
      ability to diminish in vitro lymphocyte proliferation. The purpose of this study
      was to determine if n-3 PUFA intake affects the kinetics or magnitude of the
      antigen-driven expansion of CD8(+)T-lymphocytes in vivo. In this study we
      utilized a well-characterized model of T-cell immunity (i.e. infection with the
      intracellular bacterium, Listeria monocytogenes). Weanling BALB/c mice were fed
      one of two experimental diets that differed solely in fat source. Our control
      diet contained lard (180 g/kg) and was devoid of long-chain n-3 PUFA. The
      experimental diet contained 150 g/kg menhaden fish oil and 30 g/kg corn oil, thus
      providing approximately 8 % of energy from long-chain n-3 PUFA. After 4 weeks,
      mice were infected intravenously with 10(6) colony-forming units of actA
      deficient L. monocytogenes. Clonal expansion of antigen-specific CD8(+)T-cells in
      the spleen was measured at 5, 7, 9 and 14 d post-challenge using a class I MHC
      tetramer loaded with the immunodominant peptide from this pathogen (i.e.
      K(d):LLO91-99). We report that feeding mice a diet rich in n-3 fatty acids did
      not significantly impact either the kinetics or magnitude of in vivo, antigen
      driven expansion of CD8(+)T-cells. Furthermore, contraction of this T-cell
      population was not affected by n-3 PUFA treatment. To our knowledge this is the
      first time MHC tetramers have been used to investigate the influence of n-3 PUFA
      on in vivo CD8(+)T-cell proliferation.

PMID- 16571169
TI  - Stopping the rot in nutrition science.

PMID- 16571166
TI  - Nutrition discussion forum.

PMID- 16571170
TI  - Out of the box.

PMID- 16571171
TI  - Parallel deficits in linear growth and mental development in low-income Mexican
      infants in the second year of life.
AB  - OBJECTIVE: To explore anthropometric indicators and mental development in very
      low-income children in the second year of life. DESIGN: Cross-sectional survey.
      SETTING: Low-income areas (income <20th percentile) in semi-urban Mexico (defined
      as towns or cities with 2,500-50,000 inhabitants). SUBJECTS: Eight hundred and
      ninety-six children aged 12.5-23.5 months surveyed from September to December
      2001. METHODS: Questionnaire survey and anthropometric survey of households.
      Multivariate regression models evaluated differences across age in anthropometry
      (height-for-age Z-score (HAZ) and weight-for-height Z-score) and cognitive
      function (Mental Development Index (MDI) of the Bayley Scales of Infant
      Development) while controlling for socio-economic and parental characteristics.
      RESULTS: There was a significant decline in HAZ and in age-adjusted MDI score
      across the second year of life. Although the children showed MDI scores close to
      the mean, normed US values at 13-14 months, the scores were significantly lower
      than expected in older children (P < 0.0001), even after controlling for socio
      economic status and parental characteristics. At 13-14 months, only 3% of
      children received scores below 70 (less than minus two standard deviations),
      whereas by 19-20 months, almost 17% of children were performing below this level.
      No socio-economic or parental characteristics were significant predictors of HAZ
      or MDI. CONCLUSIONS: Parallel deficits are evident in both height-for-age and
      cognitive functioning during the second year of life in low-income Mexican
      infants. The consistency of these growth and development findings further
      stresses the need for targeted interventions to reduce the vulnerability of low
      income Mexican children very early in life.

PMID- 16571172
TI  - Does living in an urban environment confer advantages for childhood nutritional
      status? Analysis of disparities in nutritional status by wealth and residence in
      Angola, Central African Republic and Senegal.
AB  - OBJECTIVE: The purpose of this paper is to examine the relationship between
      childhood undernutrition and poverty in urban and rural areas. DESIGN:
      Anthropometric and socio-economic data from Multiple Indicator Cluster Surveys in
      Angola-Secured Territory (Angola ST), Central African Republic and Senegal were
      used in this analysis. The population considered in this study is children 0-59
      months, whose records include complete anthropometric data on height, weight,
      age, gender, socio-economic level and urban or rural area of residence. In
      addition to simple urban/rural comparisons, the population was stratified using a
      wealth index based on living conditions and asset ownership to compare the
      prevalence, mean Z-score and odds ratios for stunting and wasting. RESULTS: In
      all cases, when using a simple urban/rural comparison, the prevalence of stunting
      was significantly higher in rural areas. However, when the urban and rural
      populations were stratified using a measure of wealth, the differences in
      prevalence of stunting and underweight in urban and rural areas of Angola ST,
      Central African Republic and Senegal disappeared. Poor children in these urban
      areas were just as likely to be stunted or underweight as poor children living in
      rural areas. The odds ratio of stunting in the poorest compared with the richest
      quintile was 3.4, 3.2 and 1.5 in Angola ST, Senegal and Central African Republic,
      respectively. CONCLUSIONS: This paper demonstrates that simple urban/rural
      comparisons mask wide disparities in subgroups according to wealth. There is a
      strong relationship between poverty and chronic undernutrition in both urban and
      rural areas; this relationship does not change simply by living in an urban
      environment. However, urban and rural living conditions and lifestyles differ,
      and it is important to consider these differences when designing programmes and
      policies to address undernutrition.

PMID- 16571173
TI  - Food consumption patterns in an adult urban population in Beirut, Lebanon.
AB  - OBJECTIVES: To investigate, measure and assess the food consumption pattern of
      the adult population living in Beirut, Lebanon, and to identify inadequate or
      excessive intake of food groups particularly linked to non-communicable diseases.
      DESIGN: A cross-sectional food consumption survey was conducted in 2001. Dietary
      habits were assessed by means of a quantitative food-frequency questionnaire.
      SETTING: Dietary survey of the urban population (Beirut). SUBJECTS: Random sample
      of 444 adult subjects (aged 25-54 years) in Beirut. RESULTS: The mean consumption
      of food by the study population was estimated to be 3,030 g day(-1), providing an
      energy intake of 2,523.57 kcal day(-1). Fat contributed 38.9% to the average
      daily energy intake, protein 13.4% and carbohydrates 47.2%. Mean consumption of
      fruits and vegetables was approximately 367 g day(-1) and 45.3% of subjects
      consumed less than the recommended 400 g daily. Cereals contributed 324.5 g day(
      1), providing 35.0% of daily energy intake, with bread being the most highly
      consumed (146.2 g day(-1)) in this food group. The mean intake of meat and
      poultry products was 91.7 g day(-1) and provided 8.8% of daily energy intake,
      with consumption of butchery products especially beef being the highest (47.6 g
      day(-1)) followed by poultry (36.1 g day(-1)). A low consumption of fish was
      noted (19.7 g day(-1)), with 73.6% of subjects consuming less than the
      recommended 2 servings of fish per week. Dairy products contributed 243.1 g day(
      1) or 10.9% of daily energy intake, and milk was the least consumed dairy product
      (56.8% of consumers). The intake of added fats and oils, excluding those in
      cooked recipes, was 20.4 g day(-1); olive oil was not used in cooking but was
      added solely at the table and its mean intake was 5 g day(-1). The consumption of
      butter was low (0.86 g day(-1)) and vegetable oil was the type of fat mostly used
      in cooking. The average intake of alcoholic beverages was low (33.6 g day(-1)),
      accounting for 0.7% of total energy intake. Women had significantly higher
      intakes of milk, dairy products, vegetables and coffee than men (P < 0.05). The
      percentage of women who reported the use of low-fat items was significantly
      higher than that of men. Younger people (25-34 years) ate significantly more
      meat, sugar, alcoholic beverages and soft drinks, and consumed significantly less
      cooked vegetables and legumes, than older ones (P < 0.05). CONCLUSIONS: The
      rather high contribution of fat to daily energy intake, the low intake of fish
      and the relatively high percentage of people consuming less than the recommended
      amount of fruits and vegetables observed in this study suggest that the adult
      Lebanese population is at increased risk of cardiovascular diseases, obesity and
      other non-communicable diseases, which provides the basis for recommending
      increased intakes of fish, particularly fatty fish, and fruits and vegetables.

PMID- 16571174
TI  - Disentangling women's responses on complex dietary intake patterns from an Indian
      cross-sectional survey: a latent class analysis.
AB  - OBJECTIVE: To investigate the degree of individual heterogeneity related to
      complex dietary behaviour and to further examine the associations of different
      dietary compositions with selected characteristics. DESIGN: Latent class analysis
      was applied to data from the recent cross-sectional National Family Health Survey
      that collected information on the intake frequency of selected foods. Different
      responses regarding intake frequency were condensed into a set of five meaningful
      latent clusters representing different dietary patterns and these clusters were
      then labelled based on the reported degree of diet mixing. SETTING: Indian
      states. Subjects In total, 90,180 women aged 15-49 years. RESULTS: Three clusters
      were predominantly non-vegetarian and two were vegetarian. A very high or high
      mixed-diet pattern was observed particularly in the southern and a few north
      eastern states. Many women in the very high mixed-diet cluster consumed mostly
      non-green/leafy vegetables on a daily basis, and fruits and other non-vegetarian
      diet on a weekly basis. In contrast, those in the low mixed-diet cluster consumed
      more than three-fifths of the major vegetarian diet ingredients alone on a daily
      basis. The affluent group that represented the low mixed-diet cluster were
      primarily vegetarians and those who represented the very high mixed-diet cluster
      were mostly non-vegetarians. The significant interrelationships of different
      characteristics highlight not only socio-economic, spatial and cultural
      disparities related to dietary practices, but also the substantial heterogeneity
      in diet mixing behaviour. CONCLUSIONS: The results of this study confirmed our
      hypothesis of heterogeneous dietary behaviour of Indian women and yielded useful
      policy-oriented results which might be difficult to establish otherwise.

PMID- 16571175
TI  - Eating rough: food sources and acquisition practices of homeless young people in
      Adelaide, South Australia.
AB  - OBJECTIVE: The aim of this study was to determine the food sources and
      acquisition practices used by homeless youth in Adelaide. This work is part of a
      larger study that aimed to examine the extent and nature of food insecurity among
      homeless youth. DESIGN: Cross-sectional design involving quantitative and
      qualitative methods. SETTING: Four health and welfare inner-city agencies serving
      homeless youth in Adelaide, South Australia. SUBJECTS: A sample of 150 homeless
      youth aged between 15 and 24 years recruited from these agencies. Fifteen were
      selected via snowball sampling for interview. RESULTS: Use of welfare food
      sources was high (63%). Food from welfare agencies was supplemented by unorthodox
      food acquisition methods such as theft (65%), begging for money for food (61%),
      begging for food items (44%) and asking for help from friends and relatives
      (34%). Reasons given for non-usage of welfare food services included
      affordability, access, being too busy, shame or embarrassment. CONCLUSIONS: Food
      insecurity is a salient issue for some homeless youth in Adelaide. Clarifying
      food acquisition practices of food-insecure homeless youth is essential for
      rational planning and improvement of food-related services to meet their needs.
      Such an understanding also underpins the development of broader public policy
      responses that improve individual and household skills and resources to acquire
      food and ensure food security. Nutrition professionals, welfare professionals and
      policy-makers need to work sensitively with welfare food agencies and others to
      improve food access and food security for homeless youth.

PMID- 16571176
TI  - Food insecurity in community-dwelling older Australians.
AB  - OBJECTIVE: To identify the extent of food insecurity (defined as running out of
      food in the last 12 months and being unable to afford to buy more) amongst older
      Australians, and the characteristics of those who experience this condition.
      DESIGN: Cross-sectional population survey. SETTING AND SUBJECTS: Respondents (n =
      8,881) were community-dwelling older people (65 years and older) living
      independently in New South Wales, Australia, randomly sampled to participate in a
      computer-assisted telephone interview conducted during 1999-2000. The response
      rate was 71%. Responses to a food insecurity questionnaire item were collected
      along with sociodemographic information, living arrangements, lifestyle and self
      rated health. Univariate analyses and logistic regression modelling of factors
      for reporting food insecurity were conducted. RESULTS: Approximately one in 50
      older people reported experiencing food insecurity in the previous 12 months
      attributable to inadequate finances. The analyses revealed that those at risk can
      be identified as more likely to report poorer health, limited financial
      resources, not owning their own home and living alone. Gender and age differences
      were also evident. CONCLUSION: While only a minority of older Australians
      reported experiencing food insecurity attributable to inadequate finances, such
      people are at higher risk of malnutrition and associated morbidity. Food
      insecurity is an important public health and equity issue in older people that
      can be addressed through implementing appropriate income and social support
      policies.

PMID- 16571177
TI  - Vitamin D status of 51-75-year-old Irish women: its determinants and impact on
      biochemical indices of bone turnover.
AB  - OBJECTIVES: To assess the vitamin D status of Irish postmenopausal women during
      wintertime, and to examine its relationship with serum parathyroid hormone (PTH)
      and biochemical markers of bone turnover. In addition, the determinants of
      wintertime serum 25-hydroxyvitamin D (25OH-D) levels in these women were
      investigated. DESIGN: A cross-sectional observational study. SETTING: Cork City,
      Ireland (52 degrees N). SUBJECTS: Ninety-five apparently healthy, free-living
      postmenopausal women (aged 51-75 years), not taking any medication and free from
      any condition likely to affect vitamin D status or calcium/bone metabolism.
      RESULTS: Forty-eight per cent and 7% of women had serum 25OH-D levels <50 nmol l(
      1) and <25 nmol l(-1), respectively. 25OH-D levels in these women were positively
      associated with dietary calcium intake (P = 0.0002) and use of vitamin D
      containing supplements (P = 0.031), and negatively associated with cigarette
      smoking (P = 0.027) and body mass index (BMI) (P = 0.030). Low serum 25OH-D
      levels (<50 nmol l(-1)) were associated (P < 0.01) with elevated serum PTH
      levels. There were no significant differences in urinary pyridinium crosslinks or
      serum osteocalcin, biochemical indices of bone turnover, between subjects with
      serum 25OH-D levels above or below 50 nmol l(-1). CONCLUSION: A high proportion
      of Irish postmenopausal women had low vitamin D status (<50 nmol l(-1)) during
      late wintertime, which appeared to lead to elevated levels of serum PTH but not
      of bone turnover markers. Use of regular low-dose supplemental vitamin D, meeting
      daily calcium recommendations, cessation of smoking and maintaining BMI in the
      normal range are important factors that could help maintain adequate vitamin D
      levels during wintertime in these women.

PMID- 16571178
TI  - The association between the body mass index of first-year female university
      students and their weight-related perceptions and practices, psychological
      health, physical activity and other physical health indicators.
AB  - OBJECTIVE: To investigate the association between the weight status of first-year
      female students (FYFS) and various weight management-related characteristics to
      identify possible components of a weight management programme for students.
      DESIGN: Cross-sectional study. SETTING: Female residences at a South African
      university. SUBJECTS: A total of 360 FYFS. RESULTS: Mean (+/-standard deviation
      (SD)) body mass index (BMI) of the FYFS was 21.8 +/- 2.6 kg m(-2), with 7.2%
      being underweight, 81.9% normal-weight, 10.0% overweight and 0.8% obese.
      Underweight, normal-weight and overweight students differed with regard to their
      perception of their weight (P < 0.001), weight goals (P < 0.001) and previous
      weight-loss practices (P < 0.001). Mean+/-SD score on the 26-item Eating
      Attitudes Test (EAT-26) was 8.5 +/- 9.0 with 8.4% classified as high scorers.
      Mean+/-SD score on the 34-item Body Shape Questionnaire (BSQ) was 87.7 +/- 32.2,
      with 76.1% classified as low, 11.9% as medium and 11.9% as high scorers. The self
      concept questionnaire indicated that 36.7% had a high, 43.9% a medium and 19.4% a
      low self-concept. Higher BMI correlated with a higher BSQ score (P < 0.001), a
      lower self-concept (P = 0.029) and a higher EAT-26 score (P < 0.001). Smoking was
      prevalent amongst 13.1% of students, and 51.2% used vitamin and/or mineral
      supplements. Students who quitted smoking had higher (P = 0.006) BMI (22.7 +/-
      2.9 kg m(-2)) than those who never smoked before (21.6 +/- 2.5 kg m(-2)). Normal
      weight students were more physically active than underweight or overweight
      students (P = 0.038). CONCLUSIONS: The specific weight management-related needs
      of FYFS include information about supplement use, smoking, realistic weight
      goals, safe and sound weight-loss methods, weight cycling, body-shape
      perceptions, eating attitudes and behaviours, self-concept and physical activity.
      Interventions aimed at correcting these problems should target all students,
      regardless of their BMI.

PMID- 16571179
TI  - Television viewing behaviour and associations with food habits in different
      countries.
AB  - OBJECTIVE: Several environmental factors influence adolescents' food habits and
      television (TV) viewing is thought to be one of these factors. The purpose of the
      present study was to describe sociodemographic differences in TV viewing and to
      examine associations of TV viewing with the consumption of sweets, soft drinks,
      fruit and vegetables in different countries. METHODS: Data were collected from
      162,305 young people completing the 2001/02 Health Behaviour in School-Aged
      Children survey, a World Health Organization cross-national study on health and
      health behaviours among 11-, 13- and 15-year-old school pupils. Analyses of
      variance were used to examine sociodemographic differences in TV viewing and
      logistic regression analyses to examine associations between TV viewing and food
      habits. RESULTS: Large differences were found between countries in reported daily
      TV viewing time, from an average of 2.0 h in Switzerland to 3.7 h in Ukraine. The
      results indicate that those most likely to watch TV are boys, 13-year-olds and
      pupils of lower socio-economic status. Those who watched more TV were more likely
      to consume sweets and soft drinks on a daily basis and less likely to consume
      fruit and vegetables daily, although the latter associations were not so apparent
      among Central and Eastern European countries. CONCLUSIONS: Given the high TV
      viewing rates among adolescents and the association with less healthy food
      options, many young people are at increased risk of overweight or obesity.
      Interventions to modify TV viewing behaviour are needed. The findings underscore
      the importance of tackling socio-economic differences.

PMID- 16571180
TI  - Monounsaturated fatty acids, olive oil and blood pressure: epidemiological,
      clinical and experimental evidence.
AB  - Diet has an important role in the prevention and treatment of hypertension. In
      early epidemiological studies, conducted mainly in the USA, monounsaturated fatty
      acids showed a deleterious association with blood pressure or no relationship at
      all. However, more recent studies, conducted in Mediterranean countries, have
      shed new light on this issue. In the present review we summarise the main results
      of epidemiological studies and feeding trials, and explain the possible
      mechanisms through which monounsaturated fatty acids, and specifically olive oil
      as the major dietary source of this type of fat in Mediterranean countries, could
      exert a favourable effect on blood pressure.

PMID- 16571181
TI  - Criterion-related validity of the last 7-day, short form of the International
      Physical Activity Questionnaire in Swedish adults.
AB  - OBJECTIVE: To examine the validity of the short, last 7-day, self-administered
      form of the International Physical Activity Questionnaire (IPAQ). DESIGN: All
      subjects wore an accelerometer for seven consecutive days and completed the IPAQ
      questionnaire on the eighth day. Criterion validity was assessed by linear
      regression analysis and by modified Bland-Altman analysis. Specificity and
      sensitivity were calculated for classifying respondents according to the physical
      activity guidelines of the American College of Sports Medicine/Centers for
      Disease Control and Prevention. SETTING: Workplaces in Uppsala, Sweden. SUBJECTS:
      One hundred and eighty-five (87 males) participants, aged 20 to 69 years.
      RESULTS: Total self-reported physical activity (PA) (MET-min day(-1)) was
      significantly correlated with average intensity of activity (counts min(-1)) from
      accelerometry (r = 0.34, P < 0.001). Gender, age, education and body mass index
      did not affect this relationship. Further, subcomponents of self-reported PA
      (time spent sitting, time in PA, time in moderate and vigorous activity (MVPA))
      were significantly correlated with objectively measured PA (P < 0.05). Self
      reported time in PA was significantly different from time measured by
      accelerometry (mean difference: -25.9 min day(-1); 95% limits of agreement: -172
      to 120 min day(-1); P < 0.001). IPAQ identified 77% (specificity) of those who
      met the current PA guidelines of accumulating more than 30 min day(-1) in MVPA as
      determined by accelerometry, whereas only 45% (sensitivity) of those not meeting
      the guidelines were classified correctly. CONCLUSIONS: Our results indicate that
      the short, last 7-days version of the IPAQ has acceptable criterion validity for
      use in Swedish adults. However, the IPAQ instrument significantly overestimated
      self-reported time spent in PA. The specificity to correctly classify people
      achieving current PA guidelines was acceptable, whereas the sensitivity was low.

PMID- 16571182
TI  - Is the 2000 CDC growth reference appropriate for developing countries?
AB  - In 2000, the Centers for Disease Control and Prevention (CDC) produced a revised
      growth reference. This has already been used in different settings outside the
      USA. Using data obtained during a nutritional survey in Madagascar, we compare
      results produced by using both the 2000 CDC and the 1978 National Center for
      Health Statistics (NCHS)/World Health Organization (WHO) growth references. We
      show that changing the reference has an important impact on nutritional
      diagnosis. In particular, the prevalence of wasting is greatly increased. This
      could generate substantial operational and clinical difficulties. We recommend
      continued use of the 1978 NCHS/WHO reference until release of the new WHO multi
      country growth charts.

PMID- 16571183
TI  - The Women's Health Initiative. What is on trial: nutrition and chronic disease?
      Or misinterpreted science, media havoc and the sound of silence from peers?
AB  - The first results of the Women's Health Initiative dietary intervention trial
      were published in the USA in February. This is a colossal intervention designed
      to see if diets lower in fat and higher in fruits, vegetables and grains than is
      usual in high-income countries reduce the incidence of breast cancer, colorectal
      cancer, heart disease and other chronic diseases, in women aged 50-79 years. As
      interpreted by US government media releases, the results were unimpressive. As
      interpreted by a global media blitz, the results indicate that food and nutrition
      has little or nothing to do with health and disease. But the trial was in key
      respects not reaching its aims, was methodologically controversial, and in any
      case has not produced the reported null results. What should the public health
      nutrition profession do about such messes?

PMID- 16571184
TI  - The impact of scientific misconduct on child health.

PMID- 16571185
TI  - Vending machines in schools: to ban or not to ban?

PMID- 16571186
TI  - The new nutrition: have a little faith.

PMID- 16571187
TI  - Diabetes: what about patterns, fruits, and vegetables?

PMID- 16571188
TI  - Joint project of the international network of agencies for health technology
      assessment--Part 1: Survey results on diffusion, assessment, and clinical use of
      positron emission tomography.
AB  - OBJECTIVES: The International Network of Agencies for Health Technology
      Assessment (INAHTA) has been tracking activities associated with the clinical use
      of positron emission tomography (PET) in its members' healthcare systems since
      1997 and published its first Joint Project report on PET in 1999. Part 1 of this
      Joint Project report presents survey results on diffusion, assessment activities,
      and policy for clinical use related to PET among INAHTA members since 1999.
      METHODS: INAHTA members were surveyed in 2003-2004. RESULTS: Twenty-seven INAHTA
      agencies (69 percent response rate) from nineteen countries responded to the
      survey. Dedicated PET systems are the most universally installed systems to date.
      Mobile scanners and modified gamma cameras are used occasionally as lower cost
      alternatives, and interest in PET-computed tomography hybrid models is rising
      despite limited assessment of impact on service planning. PET was used and
      assessed most commonly for managing patients with cancer. All respondents
      reported having some form of public funding for clinical PET frequently linked to
      data collection for the purpose of gathering evidence to refine clinical use and
      guide resource allocation toward indications that maximize clinical and cost
      effectiveness. CONCLUSIONS: The use of HTA within a continuous quality
      improvement framework can help optimize scarce resources for evaluation and use
      of high cost diagnostic technologies such as PET, particularly where potential
      clinical or cost-effectiveness is considerable but conclusive evidence is
      lacking.

PMID- 16571189
TI  - Joint project of the International Network of Agencies for Health Technology
      Assessment--Part 2: Managing the diffusion of positron emission tomography with
      health technology assessment.
AB  - OBJECTIVES: Since 1997, members of the International Network of Agencies for
      Health Technology Assessment (INAHTA) have collaborated on a Joint Project to
      track the diffusion, evaluation, and clinical policy of positron emission
      tomography (PET). Part 2 of this updated Joint Project report summarizes HTA
      based strategies for directing the clinical use of PET and a discussion on the
      value of HTA in managing the diffusion of high cost diagnostic technologies,
      which were presented at an INAHTA-sponsored workshop at the Health Technology
      Assessment International Annual Meeting in 2004 on strategies for managing high
      cost diagnostic technologies. METHODS: A summary of the workshop proceedings is
      presented. CONCLUSIONS: Sharing assessment work, universal agreement in
      assessment conclusions, stakeholder input, and modeling techniques help manage
      the uncertainty in the evidence base while targeting clinical use of PET toward
      the most promising indications. Emphasis on HTA findings, linkage between
      financing of clinical PET and outcome evaluation, and targeted dissemination of
      scientific findings empower providers to reduce unnecessary utilization and
      contain costs within a quality improvement framework. Above all, a trustworthy
      source of HTA information and a process that is conducive to using scientific
      evidence as the basis for decision making are essential for managing the
      diffusion of complex and costly diagnostic technologies in patient care.

PMID- 16571190
TI  - Recommendations in health technology assessments worldwide.
AB  - OBJECTIVES: The objective of this study is to analyze statistically the possible
      determinants and implications of including or not including recommendations in
      health technology assessments (HTAs). METHODS: A sample of 433 HTAs published by
      eleven leading institutions or agencies in nine countries was reviewed and
      analyzed statistically by multiple logistic regression. RESULTS: The extent of
      policy and research recommendations in HTAs varies greatly from country to
      country. The content and scope of HTAs have some impact on recommendations.
      Extensive assessment of economic and organizational aspects increases the
      likelihood of including policy recommendations. Extensive assessment of
      technological and patient aspects increases the likelihood of including research
      recommendations, whereas extensive focus on economic aspects is negatively
      related to research recommendations. The most striking result is that the use of
      external partners for assessment increases the likelihood of including research
      recommendations in HTAs but not policy recommendations. CONCLUSIONS: HTA
      commissioners, agencies, institutions, and funding authorities need to be aware
      of the consequences of the choices they make in advance of assessing health
      technologies. Outsourcing HTA to external partners suggests a greater likelihood
      of being told that "more research is needed." The scope and content of HTAs has
      an impact on the type of recommendations, and country-specific preferences are
      strong predictors of recommendations in HTAs.

PMID- 16571191
TI  - Impact of CEDIT recommendations: An example of health technology assessment in a
      hospital network.
AB  - OBJECTIVES: The objective of this study is to assess the impact of CEDIT (French
      Committee for the Assessment and Dissemination of Technological Innovations)
      recommendations on the introduction of technological innovations within the AP-HP
      (Assistance Publique-Hopitaux de Paris), the French hospital network to which
      this body is attached. METHODS: In 2002, a study based on semidirective
      interviews of fourteen people affected by these recommendations and a case study
      relating to thirteen recommendations issued between 1995 and 1998 were conducted.
      RESULTS: The CEDIT is very scientifically reputable among interviewees. There is
      generally widespread interest for the recommendations. They are used as decision
      making tools by administrative staff and as negotiating instruments by doctors in
      their dealings with management. Based on the case study, ten of thirteen
      recommendations had an impact on the introduction of the technology in health
      establishments. One recommendation appears not to have had an impact.
      Furthermore, the impact of two technologies was impossible to assess.
      CONCLUSIONS: This study highlights the significant impact of recommendations
      arising from a structure that is attached to a hospital network and the good
      match between CEDIT's objectives and its assignments.

PMID- 16571192
TI  - Integration of health technology assessment recommendations into organizational
      and clinical practice: A case study in Catalonia.
AB  - OBJECTIVES: Evaluating the impact of recommendations based upon health technology
      assessment (HTA) represents a challenge for both HTA agencies and healthcare
      policy makers. This research sought to understand factors affecting the uptake of
      HTA recommendations to support decision making with respect to the introduction
      of three health technologies. METHODS: Using a multidimensional framework, based
      upon a combination of theoretical models, a case study was conducted. A total of
      twenty-eight semistructured interviews were done with physicians from fifteen
      hospitals and other stakeholders in Catalonia. Interview content was analyzed
      iteratively and classified according to theoretical dimensions and contextual
      factors. RESULTS: At the sociopolitical level, factors related to the
      organization and financing of the health system were found to affect the
      utilization of HTA recommendations. At the healthcare organization level,
      existing collaborations between the hospital and the HTA agency favored the
      integration of recommendations into practices. Formalism in the organization also
      influenced the utilization of HTA recommendations. At the professional level, the
      high degree of autonomy of specialists, the importance of peers and collegial
      control, and the definition of professional roles and responsibilities influenced
      physicians' willingness to integrate HTA recommendations into their practice.
      CONCLUSIONS: This study offers a comprehensive framework to understand the
      complex dynamics that affect adoption of health technologies in organizational
      and professional practices. The findings suggest some avenues to promote the
      integration of HTA recommendations into practices and, thus, increase the
      utilization of scientific evidence to support decision making in health care.

PMID- 16571193
TI  - Selection of new health technologies for assessment aimed at informing decision
      making: A survey among horizon scanning systems.
AB  - OBJECTIVES: Uncertainty is pervasive in decision making on new health
      technologies; therefore, some countries have put systems in place to support
      decision makers with timely information. An important, but as yet undocumented,
      determinant of the potential value for decision making of these so-called horizon
      scanning systems (HSSs) is how the most significant health technologies are
      selected. METHODS: All thirteen member organizations of EuroScan, a collaborative
      network for HSSs, were surveyed and interviewed on how they prioritize
      technologies for assessment. RESULTS: The majority of HSSs directly serves a
      customer. Some customers actively request early assessments of new health
      technologies, thereby diminishing the need for priority setting for the HSSs. All
      systems express a concern to miss an important technology and/or to select an
      unimportant technology. Almost all HSSs use explicit selection criteria, but
      these criteria hardly ever are operationalized. The number of criteria used
      varies, but costs and health benefit of the technology are always taken into
      account. The process of reaching a final decision is implicit, undocumented in
      all but one system, and is based on agreement by consensus. CONCLUSIONS: The
      process of making the final decision on which technologies to assess can be
      improved by applying existing criteria more consistently and transparently.
      Current practice does not safeguard against missing an important technology. This
      finding is probably most important to act upon for systems with customers that do
      not actively request assessment of specific technologies.

PMID- 16571194
TI  - Diffusion of diagnostic medical devices and policy implications for India.
AB  - OBJECTIVES: This study describes the diffusion of advanced diagnostic devices in
      India and assess implications for efficiency in resource use and equity. METHODS:
      Commodity-level import statistics, household survey data, and interviews with
      medical device sellers are used to assess the spread of diagnostic devices.
      Published qualitative evidence, case studies of diagnostic service providers, and
      cross-country analyses are used to identify the reasons underlying the spread of
      medical devices in India. Case studies of public and private providers and data
      from 150 hospitals in one Indian state are used to assess efficiency in resource
      use and the distributive impacts of diagnostic devices. RESULTS: High-end medical
      device inflows rose during the 1990s, with both supply- and demand-side factors
      influencing this trend. Although our results suggest that the overall quantity of
      advanced diagnostics in India is not excessive, there is some evidence of
      inefficiency in public facilities and possibly unethical practices in private
      diagnostic facilities. The unequal geographical distribution of magnetic
      resonance imaging facilities, coupled with inefficient use of medical devices in
      public facilities suggests inequality in access. CONCLUSIONS: The study points to
      major regulatory gaps and health system inefficiencies and suggests ways in which
      these gaps can be addressed.

PMID- 16571195
TI  - Early assessment of the likely cost-effectiveness of a new technology: A Markov
      model with probabilistic sensitivity analysis of computer-assisted total knee
      replacement.
AB  - OBJECTIVES: The objective of this study is to apply a Markov model to compare
      cost-effectiveness of total knee replacement (TKR) using computer-assisted
      surgery (CAS) with that of TKR using a conventional manual method in the absence
      of formal clinical trial evidence. METHODS: A structured search was carried out
      to identify evidence relating to the clinical outcome, cost, and effectiveness of
      TKR. Nine Markov states were identified based on the progress of the disease
      after TKR. Effectiveness was expressed by quality-adjusted life years (QALYs).
      The simulation was carried out initially for 120 cycles of a month each, starting
      with 1,000 TKRs. A discount rate of 3.5 percent was used for both cost and
      effectiveness in the incremental cost-effectiveness analysis. Then, a
      probabilistic sensitivity analysis was carried out using a Monte Carlo approach
      with 10,000 iterations. RESULTS: Computer-assisted TKR was a long-term cost
      effective technology, but the QALYs gained were small. After the first 2 years,
      the incremental cost per QALY of computer-assisted TKR was dominant because of
      cheaper and more QALYs. The incremental cost-effectiveness ratio (ICER) was
      sensitive to the "effect of CAS," to the CAS extra cost, and to the utility of
      the state "Normal health after primary TKR," but it was not sensitive to
      utilities of other Markov states. Both probabilistic and deterministic analyses
      produced similar cumulative serious or minor complication rates and complex or
      simple revision rates. They also produced similar ICERs. CONCLUSIONS: Compared
      with conventional TKR, computer-assisted TKR is a cost-saving technology in the
      long-term and may offer small additional QALYs. The "effect of CAS" is to reduce
      revision rates and complications through more accurate and precise alignment, and
      although the conclusions from the model, even when allowing for a full
      probabilistic analysis of uncertainty, are clear, the "effect of CAS" on the rate
      of revisions awaits long-term clinical evidence.

PMID- 16571197
TI  - Investigating patients' preferences for cardiac rehabilitation in Denmark.
AB  - OBJECTIVES: The objective of this study was to analyze preferences for activities
      comprised in comprehensive cardiac rehabilitation programs among former cardiac
      patients from three different hospitals in Copenhagen County, Denmark. METHODS: A
      discrete choice experiment was applied to elicit the preferences for the offer of
      participation in various cardiac rehabilitation program activities: smoking
      cessation course, physical exercise program, personal meetings with cardiac
      nurse, group meetings managed by cardiac nurses, and nutritional counseling
      guidance. The questionnaire was sent to 742 former cardiac patients. We had a
      response rate of 69 percent. RESULTS: We found that preferences differed with
      respect to gender and age and that the offer of participation in cardiac
      rehabilitation activities was not highly valued by older patients, in particular
      among older men. CONCLUSIONS: The discrete choice experiment proved a valuable
      instrument for the measurement of preferences for cardiac rehabilitation. The
      study provides important information on patients' preferences for cardiac
      rehabilitation for healthcare professionals and decision makers.

PMID- 16571196
TI  - Evaluation of the ambulatory and home care record: Agreement between self-reports
      and administrative data.
AB  - OBJECTIVES: Although measuring the utilization of ambulatory and home-based
      healthcare resources is an essential component of economic analyses, very little
      methodological attention has been devoted to the development and evaluation of
      resource costing tools. This study evaluated a newly developed tool, the
      Ambulatory and Home Care Record (AHCR), which comprehensively evaluates costs
      incurred by the health system and care recipients and their unpaid caregivers.
      METHODS: The level of agreement between self-reports from 110 cystic fibrosis
      care recipients and administrative data was assessed for four categories of
      health services: home-based visits with healthcare professionals, ambulatory
      visits with healthcare professionals, laboratory and diagnostic tests, and
      prescription medications. RESULTS: Agreement between care recipients' reports on
      the AHCR and administrative data ranged from moderate (kappa = 0.41; 95 percent
      confidence interval, 0.16-0.61) for physician specialist visits to perfect (kappa
      = 1.0) for physiotherapy visits. CONCLUSIONS: By evaluating and standardizing a
      resource and costing tool, such as the AHCR, economic evaluations may be improved
      and comparisons of the resource implications for different services and for
      diverse populations are possible.

PMID- 16571198
TI  - Overview of systematic reviews on invasive treatment of stable coronary artery
      disease.
AB  - OBJECTIVES: The aim of the study was to evaluate the validity of the systematic
      reviews as a source of best evidence and to present and interpret the evidence of
      the systematic reviews on effectiveness of surgery and percutaneous interventions
      for stable coronary artery disease. METHODS: Electronic databases were searched
      without language restriction from January 1966 to March 2004. The databases used
      included the Cochrane Database of Systematic Reviews, the Cochrane Central
      Register of Controlled Trials, DARE, the Health Technology Assessment Database,
      MEDLINE(R), MEDLINE(R) In-Process & Other Non-Indexed Citations. We included
      systematic reviews of randomized clinical trials on patients with stable coronary
      heart disease undergoing percutaneous coronary intervention or coronary artery
      bypass surgery in comparison with medical treatment or a comparison between
      invasive techniques. At least one of the following outcomes had to be reported:
      death, myocardial infarction, angina pectoris, revascularization. The
      methodological quality was assessed using a modified version of the scale devised
      by Oxman and Guyatt (1991). A standardized data-extraction form was used. The
      method used to evaluate clinical relevance was carried out with updated method
      guidelines from the Cochrane Back Research Group. Quantitative synthesis of the
      effectiveness data is presented. RESULTS: We found nineteen systematic reviews.
      The median score of validity was 13 points (range, 6-17 points), with a maximum
      of 18 points. Coronary artery bypass surgery gives better relief of angina, and
      the need for repeated procedures is reduced after bypass surgery compared with
      percutaneous interventions. There is inconsistent evidence as to whether bypass
      surgery improves survival compared with percutaneous intervention. A smaller need
      for repeated procedures exists after bare metal stent and even more so after drug
      eluting stent placement than after percutaneous intervention without stent
      placement. However, according to the current evidence, these treatment
      alternatives do not differ in terms of mortality or myocardial infarction.
      CONCLUSIONS: We found some high-quality systematic reviews. There was evidence on
      the potential of invasive treatments to provide symptomatic relief. Surgery seems
      to provide a longer-lasting effect than percutaneous interventions with bare
      metal stents or without stents. Evidence in favor of drug-eluting stents so far
      is based on short-term follow-up and mostly on patients with single-vessel
      disease.

PMID- 16571199
TI  - Use of quality-adjusted life years for the estimation of effectiveness of health
      care: A systematic literature review.
AB  - OBJECTIVES: The objectives of this study were to identify, in a systematic
      literature review, published studies having used quality-adjusted life years
      (QALYs) based on actual measurements of patients' health-related quality of life
      (HRQoL) and to determine which HRQoL instruments have been used to calculate
      QALYs. Furthermore, the aims were to characterize studies with regard to medical
      specialty, intervention studied, results obtained, quality, country of origin,
      QALY gain observed, and interpretation of results regarding cost-effectiveness.
      METHODS: Systematic searches of the literature were made using the MEDLINE,
      Embase, CINAHL, SCI, and Cochrane Library electronic databases. Initial screening
      of identified articles was based on abstracts read independently by two of the
      authors; full-text articles were again evaluated by two authors, who made the
      final decision on which articles should be included. RESULTS: The search
      identified 3,882 articles; 624 were obtained for closer review. Of the reviewed
      full-text articles, seventy reported QALYs based on actual before-after
      measurements using a valid HRQoL instrument. The most frequently used instrument
      was EuroQol HRQoL instrument (EQ-5D, 47.5 percent). Other instruments used were
      Health Utilities Index (HUI, 8.8 percent), the Rosser-Kind Index (6.3 percent),
      Quality of Well-Being (QWB, 6.3 percent), Short Form-6D (SF-6D, 5.0 percent), and
      15D (2.5 percent). The rest (23.8 percent) used a direct valuation method: Time
      Trade-Off (10.0 percent), Standard Gamble (5.0 percent), visual analogue scale
      (5.0 percent), or rating scale (3.8 percent). The most frequently studied medical
      specialties were orthopedics (15.5 percent), pulmonary diseases (12.7 percent),
      and cardiology (9.9 percent). Ninety percent of the studies came from four
      countries: United Kingdom, United States, Canada, the Netherlands. Approximately
      half of the papers were methodologically high quality randomized trials. Forty
      nine percent of the studied interventions were viewed by the authors of the
      original studies as being cost-effective; only 13 percent of interventions were
      deemed not to be cost-effective. CONCLUSIONS: Although QALYs gained are
      considered an important measure of effectiveness of health care, the number of
      studies in which QALYs are based on actual measurements of patients' HRQoL is
      still fairly limited.

PMID- 16571200
TI  - Importance of appropriateness of empiric antibiotic therapy on clinical outcomes
      in intra-abdominal infections.
AB  - OBJECTIVES: The objective of this study is to describe the frequency of
      inappropriate empirical antibiotic therapy in secondary intra-abdominal infection
      and to identify the possible relationship between inappropriateness and some
      clinical outcomes. METHODS: A retrospective descriptive multicenter study was
      conducted using hospital secondary databases developed at two university
      hospitals located in northeast Spain. Participants were patients 18 years of age
      or older who were diagnosed with community-acquired intra-abdominal infections
      between January 1, 1998, and December 31, 2000, identified through computerized
      patient records using ICD-9 codes. Appropriateness of empirical treatment was
      defined according to the recommendations of the literature. The clinical outcome
      of each patient was classified as one of the following: (i) resolved with initial
      therapy, (ii) required second-line antibiotics, (iii) required re-operation, or
      (iv) in-hospital death. The Fisher's exact test or the Chi-squared test for
      categorical variables and the t-test or Mann-Whitney test for continuous
      variables were used for comparing groups. Conditional logistic and linear
      regression analyses were also applied. RESULTS: Of 376 cases, 51 cases (13.6
      percent, 95 percent confidence interval, 10-17 percent) received inappropriate
      empirical antibiotic therapy according to the scientific literature.
      Inappropriate initial empirical treatment was significantly associated with the
      need for a second line of antibiotics (p < .001), although not with re-operation,
      mortality, or length of hospitalization. CONCLUSIONS: Approximately 14 percent of
      the patients received inappropriate empirical antibiotic treatment. Worse
      clinical outcomes consistently were observed in the group of patients receiving
      inappropriate empirical treatment. The appropriateness of antibiotic treatment
      for a given infection, in light of the availability of clearly defined clinical
      guidelines is an easily evaluated aspect of the quality of care.

PMID- 16571201
TI  - Cost of an informatics-based diabetes management program.
AB  - OBJECTIVES: The relatively high cost of information technology systems may be a
      barrier to hospitals thinking of adopting this technology. The experiences of
      early adopters may facilitate decision making for hospitals less able to risk
      their limited resources. This study identifies the costs to design, develop,
      implement, and operate an innovative informatics-based registry and disease
      management system (POPMAN) to manage type 2 diabetes in a primary care setting.
      METHODS: The various cost components of POPMAN were systematically identified and
      collected. RESULTS: POPMAN cost 450,000 dollars to develop and operate over 3.5
      years (1999-2003). Approximately 250,000 dollars of these costs are one-time
      expenditures or sunk costs. Annual operating costs are expected to range from
      90,000 dollars to 110,000 dollars translating to approximately 90 dollars per
      patient for a 1,200 patient registry. CONCLUSIONS: The cost of POPMAN is
      comparable to the costs of other quality-improving interventions for patients
      with diabetes. Modifications to POPMAN for adaptation to other chronic diseases
      or to interface with new electronic medical record systems will require
      additional investment but should not be as high as initial development costs.
      POPMAN provides a means of tracking progress against negotiated quality targets,
      allowing hospitals to negotiate pay for performance incentives with insurers that
      may exceed the annual operating cost of POPMAN. As a result, the quality of care
      of patients with diabetes through use of POPMAN could be improved at a minimal
      net cost to hospitals.

PMID- 16571202
TI  - Managing urgent surgery as a process: Case study of a trauma center.
AB  - OBJECTIVES: Industrial management principles could be used to improve the quality
      and efficiency of health care. In this study, we have evaluated the effects of a
      process management approach to trauma patient care. The major objective was to
      reduce the waiting times and increase the efficiency of the hospital. METHODS:
      Urgent surgery care was analyzed as an overall process. The process development
      followed the Plan-Do-Check-Act (PDCA) cycle and was based on statistical analysis
      of certain performance metrics. Data were collected from hospital databases and
      by personnel interviews. To develop the process, the anesthesia induction was
      performed outside the operating room, better process guidance was developed, and
      patient flow was reorganized. The transition time for these changes was 1 year
      (2002 to 2003). RESULTS: Waiting times decreased by 20.5 percent (p < .05),
      nonoperative times in the operating room were reduced by 23.1 percent (p < .001),
      and efficiency was increased by 9.7 percent (p < .001) after reengineering of the
      care process. Overtime hours decreased by 30.9 percent. CONCLUSIONS: Managing
      urgent surgical care as a process can improve the productivity and quality of
      care without a need to increase personnel resources. The focus should be on
      reducing waiting times and waste times.

PMID- 16571203
TI  - Noninferiority testing in cost-minimization studies: Practical issues concerning
      power analysis.
AB  - OBJECTIVES: In cost-minimization studies, it is important to establish
      noninferiority in the clinical effect of the treatments under investigation. The
      relationship between the proportion of patients reaching the end point in a
      study, equivalence limit (delta), and power is investigated in the context of
      cost-minimization studies with dichotomous clinical end points. Two formulations
      of the null-hypothesis, absolute and relative formulations of delta, will be
      explored. METHODS: Sensitivity analysis was performed, in which the effect of the
      predicted proportions and delta on the power in a noninferiority setting was
      investigated. The patterns found are discussed in terms of the practical
      relevance within the cost-minimization framework. RESULTS: Sensitivity analyses
      show different patterns of results for both null-hypotheses. The differences in
      these results originate from the way delta is expressed. By expressing delta as
      absolute difference, power grows quite fast when sample proportions are smaller
      than expected. In the case of a proportional delta at small sample proportions,
      the power to establish noninferiority remains low. CONCLUSIONS: To obtain valid
      results from a cost-minimization study, care has to be taken to adapt the correct
      methodology for noninferiority testing in clinical outcomes. Defining delta in
      terms of absolute differences between treatments can lead to obscured results.
      Although conservative, the expression of delta as a proportion of the
      effectiveness of the treatment as usual is found to be closer to clinical
      practice. The inflated delta, resulting from smaller clinical effects than
      expected when absolute formulation is applied, thus can be avoided.

PMID- 16571204
TI  - Author contacts for retrieval of data for a meta-analysis on exercise and diet
      restriction.
AB  - OBJECTIVES: The mode of contact and response levels of authors who had been asked
      to provide missing or incomplete data for a systematic review on diet and
      exercise interventions for weight loss was examined. METHODS: We contacted
      authors by electronic mail, letter, or both. Survival analyses were performed
      with the Kaplan-Meier method to determine differences in the proportion of
      responders over time among the different modes of contact and to determine
      whether response rates differed between authors from the United States and those
      from other countries. Logistic regression was used to determine whether the
      number of items requested and publication date influenced the likelihood of
      response. RESULTS: Two hundred forty-one (39.9 percent) studies had missing or
      incomplete data (e.g., sample size, age, caloric restriction, exercise amount,
      and so on). We were unable to locate ninety-five authors (39.4 percent). Of the
      remaining authors, forty-six authors (31.5 percent) responded to information
      requests. Time to respond differed by contact method (p < .05): e-mail (3 +/- 3
      days), letter (27 +/- 30 days), and both (13 +/-12 days). Response rates from
      U.S. authors did not differ from those of other countries. CONCLUSIONS: Our study
      suggests poor success in the acquisition of essential information. Given
      considerable time and resources, weight loss studies require improved reporting
      standards to minimize the relatively unsuccessful attempt to contact authors for
      important and necessary information.

PMID- 16571270
TI  - Effect of benzophenones from Hypericum annulatum on carbon tetrachloride-induced
      toxicity in freshly isolated rat hepatocytes.
AB  - Five benzophenones and a xanthone, isolated from Hypericum annulatum Moris, were
      investigated for their protective effect against carbon tetrachloride toxicity in
      isolated rat hepatocytes. The benzophenones and the xanthone gentisein were
      administered alone (100 microM) and in combination with CCl4 (86 microM). CCl4
      undergoes dehalogenation in the liver endoplasmic reticulum. This process leads
      to trichlormethyl radical (*CCl3) formation, initiation of lipid peroxidation,
      and measurable toxic effects on the hepatocytes. The levels of thiobarbituric
      acid reactive substances (TBARS) were assayed as an index of lipid peroxidation
      (LPO). Lactate dehydrogenase (LDH) leakage, cell viability and reduced
      glutathione (GSH) depletion were used as signs of cytotoxicity. CCl4
      significantly decreased hepatocyte viability, GSH level and increased TBARS level
      and LDH leakage as compared to the control. Our data indicate that 2,3',5',6
      tetrahydroxy-4-methoxybenzophenone, 2-O-alpha-L-arabinofuranosyl-3',5',6
      trihydroxy-4-methoxybenzophenone and 2-O-alpha-L-3'-acetylarabinofuranosyl
      3',5',6-trihydroxy-4-methoxybenzophenone showed weaker toxic effects compared to
      CCl4 and in combination showed statistically significant protection against the
      toxic agent.

PMID- 16571271
TI  - Direct measurement of the rate of glutathione synthesis in 1-chloro-2,4
      dinitrobenzene treated human erythrocytes.
AB  - Cell glutathione scavenges free radicals, degrades peroxides, removes damaging
      electrophiles and maintains the redox state. The aim of this study was to develop
      an effective and efficient method to measure the rate of glutathione synthesis
      from its constituent amino acids in whole erythrocytes (RBCs). RBCs (10%
      haematocrit) were exposed to 0.3 mM 1-chloro-2,4-dinitrobenzene (CDNB) to lower
      their total glutathione content by 70% and then incubated with glucose, and N
      acetylcysteine as a cysteine source. Over 3 h, glutathione levels increased at a
      constant rate of 1.2 micromol (L RBC)(-1)min(-1), almost 5 times faster than the
      rate of glutathione synthesis in RBCs with normal glutathione levels. Glutathione
      at concentrations normally found in RBCs is known to inhibit glutamate cysteine
      ligase (the major rate controlling enzyme for glutathione synthesis). The rate of
      glutathione recovery was substantially reduced in RBCs treated with buthionine
      sulfoximine, a specific inhibitor of glutamate cysteine ligase. Our results
      indicate that the measurement of glutathione recovery rate after CDNB treatment
      can be used to estimate de novo synthesis of glutathione. Application of this
      direct method for measuring glutathione synthesis will increase understanding of
      the interactions of effectors that determine glutathione levels in RBCs under
      various physiological and pathological conditions.

PMID- 16571273
TI  - Di-imine copper(II) complexes as redox mediator and modulator in 2-deoxy-D-ribose
      oxidative damage.
AB  - Redox properties of copper complexes are important for their catalytic functions
      in vitro and in biological systems, and can contribute to their reactivity toward
      selected targets. In order to evaluate the influence of different ligands on the
      reactivity of copper ions, comparative studies were carried out with some
      copper(II) complexes containing a tridentate imine, or a tetradentate di-Schiff
      base ligand with a mixed pyridine, pyrazine, or imidazole donor set, acting as
      catalysts in the oxidation of 2-deoxy-D-ribose. Addition of the reducing agent
      glutathione (gamma-glutamylcysteinylglycine; GSH), which can also act as a good
      ligand for copper(I), mediated the oxidation of the substrate. For some of these
      compounds, a reductive activation followed by competition for the metal ion was
      verified, with formation of copper(I)-glutathione complex monitored by
      fluorescence measurements. For others, however, the reduction of the metal by the
      glutathione seems to not occur. In the presence of hydrogen peroxide, the
      oxidative damage is significantly enhanced for all the complexes tested. Redox
      potential measurements by cyclic voltammetry corroborated partially these
      results, indicating that the most reactive complexes are those with more positive
      redox potential. Evidence for site-specific attack to 2-deoxy-D-ribose was also
      observed, consistent with the intermediary formation of a copper-hydroxyl
      species, [LCu(II)(*OH)], rather than 'free' hydroxyl radical.

PMID- 16571272
TI  - Reactions of the melatonin metabolite N1-acetyl-5-methoxykynuramine (AMK) with
      the ABTS cation radical: identification of new oxidation products.
AB  - The melatonin metabolite N1-acetyl-5-methoxykynuramine (AMK; 1), which was
      previously shown to be a potent radical scavenger, was oxidized using the ABTS
      cation radical [ABTS = 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid)].
      Several new oxidation products were obtained, which were separated by repeated
      chromatography and characterized by spectroscopic methods such as mass
      spectrometry (ESI-MS and ESI-HRMS), 1H-NMR and 13C-NMR, HMBC, HSQC, H,H COSY
      correlations and IR spectroscopy. The main products were oligomers of 1 (3
      dimers, 1 trimer and 2 tetramers). In all cases, the amino group N2 was involved
      in the reactions. Two of the dimers turned out to be cis (2a) and trans (2b)
      isomers containing an azo bond. In the other dimer (3a), the nitrogen atom N2 was
      attached to atom C5 of the second aromatic amine, with loss of the methoxy group.
      In the trimer (5), one N2 formed a bridge to C5 of unit B, as in the respective
      dimer, while this one of C had bridged to C6 of B. One of the tetramers (6) was
      composed of a trimer 5 attached to N2 of a fourth 1 molecule via an azo bond as
      in 2a/b. In the other tetramer (7), an additional C-C bond between rings B and C
      in 6 is assumed. Although oligomers of AMK may only attain low in vivo
      concentrations, the types of reactions observed shed light on the physiologically
      possible metabolism of AMK once reacted with a free radical. The displacement of
      a methoxy group, rarely seen in the oxidation of methoxylated biomolecules,
      underlines the reactivity of AMK (1). Preliminary data show that, in the presence
      of ABTS cation radicals, AMK (1) can interact with side chains of aromatic amino
      acids, a finding which may be crucial for understanding to date unidentified
      protein modification by a melatonin metabolite detected earlier in experiments
      with radioactively labeled melatonin.

PMID- 16571274
TI  - Systemic NF-kappaB activation in blood cells of breast cancer patients.
AB  - There is a well-established role for reactive oxygen and nitrogen species,
      chronic inflammation and immune response in the pathogenesis of breast cancer.
      Complex interactions between breast cancer cells and surrounding blood vessels
      are prerequisites for cancer growth and invasion. Reports in the literature
      concerning the systemic response to, and the effect of, common breast cancer
      therapy on NF-kappaB and antioxidative defence enzyme expression and activity
      under clinical conditions are scarce. We determined these parameters in whole
      blood cell lysate from 16 women with breast cancer before and after combined
      (cyclophosphamide, doxorubicin, 5-fluorouracil; CAF) therapy and compared the
      results with 16 healthy women. Significantly higher levels of NF-kappaB and Mn
      SOD (both their protein level and their activity) were found in breast cancer
      patients before and after CAF therapy, in comparison with healthy women. In
      parallel measurements, no change in the level or activity of catalase (CAT) was
      detected. According to our findings, it appears that breast cancer creates
      conditions that increase the level of hydrogen peroxide in the circulating cells
      and that the applied CAF therapy fails to compensate, therefore creating systemic
      conditions that favour survival and invasion of breast cancer cells.

PMID- 16571275
TI  - Clinical study on effect of electro-acupuncture combined with different
      anesthetics on auditory-evoked potential index.
AB  - OBJECTIVE: To observe the effect of electro-acupuncture (EA) on auto regressive
      with exogenous input model (ARX-model) auditory evoked index (AAI) in patients
      anesthetized with different anesthetics. METHODS: Forty-eight adult patients
      undergoing scheduled surgical operation were enrolled and divided into two groups
      (24 in each group) according to the anesthetics applied, Group A was anesthetized
      with propofol sedation and Group B with Isoflurane-epidural anesthesia. Group A
      was subdivided into three groups of low, middle and high concentration of target
      effect-site of 1.0 microg/ml, 1.5 microg/ml and 2.0 microg/ml through target
      controlled infusion (TCI) and Group B into 3 subgroups of minimum alveolar
      effective concentration of isoflurane (0.4 MAC, 0.6 MAC and 0.8 MAC for B1, B2
      and B3 subgroups) respectively, with 8 patients in every subgroup. EA on
      acupoints of Hegu (LI4) and Neiguan (P6) was applied on all the patients during
      anesthesia, and the change of AAI at various time points was recorded. RESULTS:
      In the three subgroups of Group A, levels of AAI were significantly elevated in
      the first few minutes after EA, and significantly lowered 20 min after EA in
      subgroup A2. While in the subgroups of Group B, except the elevating in Group B1
      1-2 min after EA, levels of AAI remained unchanged at other time points.
      CONCLUSION: Pain response could be reflected by AAI during EA. EA could enhance
      the sedative effect of propofol in middle concentration, but its effect on
      isoflurane epidural anesthesia is insignificant.

PMID- 16571276
TI  - Randomized double-blinded and controlled clinical trial on treatment of HIV/AIDS
      by Zhongyan-4.
AB  - OBJECTIVE: To assess the efficacy and safety of Zhongyan-4 (ZY-4, a Chinese
      herbal preparation worked out according to the therapeutic principle of
      supplementing qi, nourishing Yin, clearing heat and detoxication) in treating
      HIV/AIDS patients in the early or middle stage. METHODS: Adopted was randomized
      double-blinded and placebo-parallel-controlled method, with 72 HIV/AIDS patients
      randomly divided into the ZY-4 group (36 patients) treated with ZY-4 and the
      control group (36 patients) treated with placebo. The treatment course was six
      months. The index of CD(4)(+), CD(8)(+) counts, body weight, clinical symptom
      scoring were estimated at 4 time points (0, 1, 3 and 6 month in the course), and
      also the viral load before and after treatment. The whole course of observation
      was completed in 63 patients, 30 in the ZY-4 group and 33 in the control group.
      RESULTS: CD(4)(+) count in the ZY-4 group got elevated by 7.70 +/- 150.96/mm(3)
      on average, while that in the control group lowered by 27.33 +/- 85.28/mm(3).
      Fifteen out of the 30 patients in the ZY-4 group had their CD(4)(+) count
      increased, which was evidently much higher than that in the control group (8/33,
      P < 0.05), suggesting that the efficacy of ZY-4 is superior to that of placebo in
      elevating CD(4)(+) count. Moreover, ZY-4 showed actions in elevating CD(45)RA(+)
      and CD(8)(+) count, reducing HIV virus load, improving clinical symptom/sign and
      increasing body weight of patients. No obvious adverse reaction was found in the
      clinical trial. CONCLUSION: ZY-4 has an immunity-protective and/or rebuilding
      function in HIV/AIDS patients in the early and middle stage, and also shows
      effects in lowering viral load, increasing body weight and improving symptoms and
      signs to a certain degree.

PMID- 16571277
TI  - Clinical non-inferiority trial on treatment of coronary heart disease angina
      pectoris of Xin-blood stasis syndrome type with lyophilized Salvia salt of
      lithospermic acid powder for injection.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of lyophilized Salvia salt of
      lithospermic acid powder for injection (SSLA) in treating coronary heart diseases
      angina pectoris (CHD-AP) of Xin-blood stasis syndrome type, and to conduct the
      non-inferiority trial with Danshen injection (DSI) as positive control. METHODS:
      An non-inferiority clinical layered, segmented, randomized, and blinded trial on
      three parallel and multiple centered groups was conducted in 480 patients with
      stable effort angina grade I, II and III, who had two or more times of attack
      every week. The 240 patients in test group A were treated with SSLA 200 mg added
      in 250 ml of 5% glucose solution for intravenous dripping every day; the 120
      patients in test group B were treated with SSLA but the dosage doubled; and the
      120 patients in the control group were treated with DSI 20 ml daily in the same
      method as SSLA was given. The clinical effectiveness and safety were evaluated
      after the patients were treated for 14 days. RESULTS: The results showed that the
      markedly effective rate in test groups A, B and control group was 37.45%, 36.75%
      and 30.09% respectively, while the total effective rate in them was 88.09%,
      89.74% and 67.26% respectively. Statistical significance was shown in comparisons
      of the therapeutic effect between control group with test group A and test group
      B, with that in the two test groups superior to that in the control group, and
      non-inferiority trial showed eligibility (P < 0.01). Adverse reaction appeared in
      8 patients in the test groups and 2 in the control group. CONCLUSION: SSLA has
      definite therapeutic effect in treating patients with CHD-AP, with its effect not
      inferior to that of DSI, and no evident toxic-adverse reaction.

PMID- 16571278
TI  - Clinical study of Jiawei Huangqi Guizhi Wuwu Decoction in preventing and treating
      peripheral neuro-sensory toxicity caused by oxaliplatin.
AB  - OBJECTIVE: To evaluate the efficacy of Jiawei Huangqi Guizhi Wuwu Decoction
      (JHGWD) in treating neuro-sensory toxicity induced by oxaliplatin. METHODS: A
      randomized controlled self-crossover trial was performed. Thirty-one patients
      were randomly divided into AB and BA groups. Patients in A cycle belonged to the
      treated group, who were treated with chemotherapy combined with oxaliplatin plus
      JHGWD. Patients in B cycle belonged to the control group and were treated with
      chemotherapy alone. The peripheral neuro-sensory toxicity was observed and
      analyzed. RESULTS: The main neurotoxicity was cold-induced paresthesia after the
      use of oxaliplatin, which included hyperaesthesia, chill, anaesthesia in the
      extremities, electrified sensation, formication, foreign body sensation and pain
      that might be exacerbated by exposure to cold. Twenty patients (64.5%) suffered
      from neuro-sensory toxicity in the treated group and 27 cases (87.1%) in the
      control group. Symptoms were more serious and lasted longer in the control group
      than those in the treated group (P < 0.01). CONCLUSION: JHGWD could prevent and
      reduce the occurrence and intensity of acute peripheral neuro-sensory toxicity
      caused by oxaliplatin.

PMID- 16571279
TI  - Effect of Taizhi'an capsule combined with Simvastatin on hyperlipidemia in
      diabetic patients.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of Taizhi'an (TZA) capsule
      combined with Simvastatin (Sim) in treating hyperlipidemia in diabetes mellitus
      (DM) patients. METHODS: Eighty cases of type 2 DM patients with hyperlipidemia
      were randomized into two groups, 40 in each group. The patients in the treated
      group took orally TZA capsules at the dose of 0.9 g 3 times a day and Sim 10 mg
      at bedtime. And the patients in the control group were treated with Sim 20 mg
      alone at bedtime. Both regimens lasted for 12 weeks. Before and after the study
      the changes of blood lipid levels and adverse reaction were investigated.
      RESULTS: The serum levels of total cholesterol (TC), triglycerides (TG) and low
      density lipoprotein-cholesterol (LDL-C) were decreased respectively by 28.8%,
      18.2% and 26.3% in the treated group; and by 29.4%, 19.4% and 24.6% in the
      control group. On the contrary, high density lipoprotein-cholesterol (HDL-C) was
      increased by 23.5% in the treated group and by 29.4% in the control group. All
      these changes were statistically significant before and after treatment (all P <
      0.05), but they did not differ statistically between the two groups (P > 0.05).
      There was no significant changes in hemoglobin A(1)c (HbA(1)c). Patients in the
      treated group did not develop any adverse reactions. However, ALT was found to be
      higher above the normal range in 5% of the patients in the control group.
      CONCLUSION: In treating hyperlipidemia in DM patients, combination of TZA with
      Sim 10 mg taken daily achieved satisfactory efficacy which was similar to Sim 20
      mg daily alone. But the combination therapy conducted in the treated group proved
      to be better in safety, and could overcome adverse reactions resulting from Sim
      that was seen in the control group.

PMID- 16571280
TI  - Effect of astragalus injection on serious abdominal traumatic patients' cellular
      immunity.
AB  - OBJECTIVE: To explore the change of serious abdominal traumatic patients'
      cellular immunity and the effect of Astragalus Injection (AI) on it. METHODS:
      Sixty-three serious abdominal traumatic patients were randomly assigned into two
      groups, the conventional group and the treated group, patients in the
      conventional group were given conventional treatment, while others in the treated
      group were given conventional treatment as the basis, with AI 20 ml was added
      into 250 ml of 5% glucose solution given through intravenous dripping, and then
      on the first day and 14th day, their T cell activated antigens as well as that of
      10 healthy subjects were monitored. RESULTS: On the first day, in the
      conventional group and treated group, the levels of CD(3)(+), CD(4)(+),
      CD(4)(+)/CD(8)(+), CD(16)(+), CD(69)(+) and CD(3)(+)/homologous leucocytic
      antigen-DR (HLA-DR(+)) were apparently lower than those in the healthy group (P <
      0.05), while the CD(8)(+) was significantly higher than that in the healthy group
      (P < 0.05), and there was no significant difference between the conventional
      group and the treated group (P > 0.05); on the 14th days, the levels of CD(3)(+),
      CD(4)(+), CD(4)(+)/CD(8)(+), CD(16)(+), CD(69)(+) and CD(3)(+)/HLA-DR(+) of the
      treated group got closed to healthy subject value, and got even higher than those
      of conventional group (P < 0.05); CD(8)(+) got close to that of healthy subjects,
      while obviously lower than that of conventional group (P < 0.05). CONCLUSION:
      After serious abdominal trauma, cellular immunity lowered, auxiliary use of AI
      was beneficial to the restoration of cellular immunity.

PMID- 16571281
TI  - Intervention of Tongxinluo capsule against vascular lesion of atherosclerosis and
      its effect on lectin-like oxidized low density lipoprotein receptor-1 expression
      in rabbits.
AB  - OBJECTIVE: To investigate the prevention by Tongxinluo capsule (TXL) of vascular
      lesions and its effect on the levels of protein and gene expression of lectin
      like oxidized low-density lipoprotein receptor-1 (LOX-1) of vascular wall in
      rabbits with atherosclerosis (AS), and to explore its possible mechanism against
      AS. METHODS: AS models were established by feeding New Zealand white rabbits with
      high-cholesterol diet, and 24 immature rabbits were randomly divided into the
      control group, model group and treated group (treated with TXL capsule). The
      indexes of total cholesterol (TC) and low density lipoprotein (LDL) levels were
      measured at the 16th week. The intima thickness and the plaque area of abdominal
      aorta were quantitatively analyzed by pathological morphological analysis, the
      expression of macrophage and smooth muscle cell (SMC) in intima were detected by
      immunohistochemical method and histologic segments were stained by Hematoxilin
      Eosin (HE) to identify the degree of atherosclerotic lesion in the model group
      and the prevention by TXL. The LOX-1 gene and protein expression in abdominal
      aorta was detected by semi-quantitative RT-PCR and immunohistochemistry,
      respectively. RESULTS: In the model group, the levels of TC and LDL were
      significantly elevated, aortic intima thickened extensively, the intima area
      enhanced, and macrophages expression increased; the levels of LOX-1 gene and
      protein expression was up-regulated in endothelium and neo-intima of the
      abdominal aorta. The treatment with TXL reduced blood lipids, attenuated arterial
      intimal proliferation, markedly inhibited the expression of macrophage and
      excessively expressed the level of LOX-1. CONCLUSION: TXL has an inhibitory
      effect on blood lipids, and it can prevent the occurrence of vascular lesion and
      cure its development, and its protection against AS was possibly associated with
      a crucial endothelial protective action through lowering the expression of LOX-1
      in vascular walls.

PMID- 16571282
TI  - Protective effect of Ginkgo biloba leaf extract on learning and memory deficit
      induced by aluminum in model rats.
AB  - OBJECTIVE: To examine the protective effect of Ginkgo biloba leaf extract (GbE)
      on learning and memory deficit induced by aluminum chloride (AlCl(3)), and
      explore its mechanisms. METHODS: The rat models with learning and memory deficit
      were induced by administering via gastrogavage and drinking of AlCl(3) solution.
      And the model rats were treated with GbE at the dose of 50, 100, 200 mg/kg every
      day for 2 months accompanied with drinking of AlCl(3) solution, respectively.
      Their abilities of spatial learning and memory were tested by Morris water maze,
      and the acetylcholinesterase (AChE) activity in serum was assayed with chemical
      method, the AChE expression in hippocampus was observed by immunohistochemistry
      assay, and then quantitative analysis was done by BI 2000 image analysis system.
      RESULTS: Learning and memory deficit of rats could be induced by AlCl(3) solution
      (P < 0.01), and AChE expressions in rats hippocampus were increased (P < 0.01);
      GbE ameliorated learning and memory deficit and reduced AChE expression in rats
      hippocampus in a dose-dependent manner, while GbE significantly increased serum
      AChE activity at the dose of 200 mg/kg each day (P < 0.05). CONCLUSION: GbE can
      ameliorate learning and memory deficit induced by AlCl(3), which may be due to
      its inhibition of the AChE expression in hippocampus.

PMID- 16571283
TI  - Thermodynamic study on antibacterial effect of different extracts from Radix
      Isatis.
AB  - OBJECTIVE: To study and analyze the antibacterial effects of different extracts
      from Radix Isatis. METHODS: Staphylococcus aureus was used as the studied object
      in the experiment. Antibacterial effects of extracts from Radix Isatis were
      observed by thermocalrimetry on Staphylococcus aureus, together with common
      pharmacological experiments. RESULTS: The total extract, ethyl acetate (EtOAc)
      extract, n-butylalcohol (nBuOH) extract, chloroform (CHCl(3)) extract and
      petroleum (P.E.) extract had antiviral effects to some extent while the residue
      after extracting had no antibacterial activity. The potency of antiviral activity
      among them was as follows: nBuOH extract > EtOAc extract > CHCl(3) extract >
      total extract > P.E. extract. CONCLUSION: The antibacteriall effects of Radix
      Isatis were not limited to any active portion, showing that Radix Isatis exerts
      its antibacterial effects by cooperation of different active fractions in varied
      ways.

PMID- 16571284
TI  - Effect of Yangqixue Qufengshi Recipe on rheumatoid arthritis model mice under
      different genetic backgrounds.
AB  - OBJECTIVE: To study the effect of Yangqixue Qufengshi Recipe (YQXQFS) on
      rheumatoid arthritis (RA) model mice under different genetic backgrounds.
      METHODS: Collagen Induced Arthritis (CIA) were established on HLA-DR4 transgenic
      (TG) mice and non-transgenic (NTG) mice, which partly were raised with YQXQFS,
      and the onset day of CIA, the level of type II collagen (CII)-reactive antibodies
      and the pathological scores of CIA were assessed. RESULTS: Under HLA-DR4 TG
      background (compared with NTG mice), the earlier onset day of CIA (11.22 +/- 3.35
      days vs 16.56 +/- 4.75 days, P < 0.05) and higher level of CII-reactive
      antibodies (0.2274 +/- 0.1390 microg/ml vs 0.1101 +/- 0.0560 microg/ml, P < 0.05)
      were observed, but the pathological scores of CIA remained unchanged. YQXQFS
      could not influence the onset day of CIA and the level of CII-reactive
      antibodies, but had a certain effect on the total pathological scores (6.56 +/-
      3.43 scores vs 11.11 +/- 5.64 scores) and bone erosion (0.22 +/- 0.44 scores vs
      1.67 +/- 1.50 scores) of CIA on NTG mice (P < 0.05), NTG YQXQFS group compared
      with NTG experimental group. CONCLUSION: YQXQFS had a certain effect on RA model,
      but had no significant effect on HLA-DR4 related CIA.

PMID- 16571290
TI  - An ageusia and dysosmia patient treated by acupuncture.

PMID- 16571285
TI  - Improvement of quality of life with Shenfu injection in non small cell lung
      cancer patients treated with gemcitabine plus cisplatin regimen.
AB  - OBJECTIVE: To observe the effect of Shenfu injection (SFI) in treating non small
      cell lung cancer (NSCLC) patients on quality of life with gemcitabine (GEM) plus
      cisplatin (GP) regimen. METHODS: Thirty-four patients were ready to receive GP
      regimen chemotherapy for treating NSCLC disease, according to lot-drawing, they
      were divided into SFI pre-treatment group (18 cases) and SFI post-treatment group
      (16 cases). SFI pre-treatment group: During the first treatment course,
      chemotherapy was begun with SFI 60 ml, intravenous dripping on the 3rd day, once
      daily, consecutively for 10 days; on the 1st day, GP regimen (GEM 1250 mg/m(2),
      intravenous dripping, on the 1st and 8th day; cisplatin 70 mg/m(2) on the 2nd
      day; 21 days as one cycle) was carried out; in the second treatment course GP
      regimen was merely given to serve as the self-control. SFI post-treatment group:
      the medicament sequence order was reversed from that of pre-treatment group.
      Using dual international quality of life (QOL) scores, the effect of SFI on the
      patients' QOL was observed through randomized self pre- and post-crossover
      control. RESULTS: The QOL in the 34 patients after being treated by SFI in
      combination with GP chemotherapy regimen in one group, and GP chemotherapy
      regimen alone in the other, was improved in different degrees, with significant
      difference (P < 0.01); comparison of SFI combined with GP chemotherapy regimen
      with GP chemotherapy alone showed that QOL in patients was significantly
      different (P < 0.01). CONCLUSION: SFI could improve QOL in patients with NSCLC
      who were treated with GP regimen.

PMID- 16571286
TI  - Treatment of severe post-kidney-transplant lung infection by integrative Chinese
      and Western medicine.
AB  - OBJECTIVE: To explore treatments of severe post-kidney-transplant lung infection
      by integrative Chinese and Western medicine (ICWM), in order to elevate the
      curing rate as well as to lower the death rate. METHODS: Based on conventional
      ways of Western medical treatments of 18 cases of severe post-kidney-transplant
      lung infection, such as putting the patients in single individual ward,
      antibiotics to prevent infection, respiratory machines, blood filtration,
      nutritional support, steroids, and maintaining electrolytes balance, we applied
      integrated Chinese medicinal treatments, like altering conventional prescription
      "pneumonia III", and conducted clinical observation of effectiveness, and indexes
      including white blood cell (WBC), neutrophilic granulocyte, blood urea nitrogen
      (BUN), blood creatinine (Cr), etc. RESULTS: Of the 18 cases studied, 7 were
      already cured, 8 proved the treatment effective, 3 died. All clinical indexes had
      statistically significant changes compared with those of before treatment (P <
      0.01). CONCLUSION: ICWM can increase curing rate and lower death rate.

PMID- 16571292
TI  - General survey of traditional Chinese medicine and Western medicine researches on
      tumor metastasis.
AB  - Metastasis and recurrence of tumors is the chief cause of death for such
      patients. Therefore, researches on the mechanism of its metastasis, prevention
      and treatment are the focal points in the field of traditional Chinese medicine
      (TCM) and Western medicine (WM) at present. WM practitioners' study on tumor
      metastasis involved its occurrence and development including every detail and
      process, and now it even has developed into the molecular biological field. In
      treatment surgical operation and radio-chemotherapy is used as the main means,
      but the efficacy is not too optimistic. In recent years, TCM, as part of the
      comprehensive therapy, has been gradually gaining attention of oncologists. Aimed
      at solving the difficult problems in metastasis of tumor, many TCM practitioners
      on the basis of syndrome differentiation have raised theories about the cause of
      tumor metastasis. On the basis of these theories, some TCM recipes against tumor
      metastasis have been developed to serve as an effective supplement to surgical
      operation, radio- and chemotherapy. The present article summarizes research
      results in recent years about the cause of formation of tumor and its metastasis
      by TCM and WM, so as to offer some theoretical clues to the study of tumor's
      metastasis.

PMID- 16571291
TI  - Current status of clinical and experimental researches on cognitive impairment in
      diabetes.
AB  - This article reviews the clinical and experimental researches on cognitive
      impairment related to diabetes in the recent decade. Most clinical studies
      indicate that the cognitive impairment in patients with type 1 diabetes mellitus
      is related to recurrent hypoglycemia closely. There is little research about
      whether or not hyperglycemia is related to cognitive impairment in patients with
      type 1 diabetes mellitus. Most studies indicate that the cognitive impairment in
      type 2 diabetes involves multiple factors through multiple mechanisms, including
      blood glucose, blood lipid, blood pressure, level of insulin, medication, chronic
      complication, etc. But, there has been no large-scale, multi-center, randomized
      controlled clinical trial in China recently. And what is more, some problems
      exist in this field of research, such as the lack of golden criterion of
      cognitive function measurement, different population of studied objects, and
      incomprehensive handling of confounding factors. Experimental studies found that
      hippocampal long-term potentiation (LTP) was impaired, which were manifested by
      impairment of spatial memory and decreased expression of LTP, but it's relation
      to hyperglycemia, the duration of diabetes, learning and memory has always been
      differently reported by different researches. Thus, there are a lot of unknown
      things to be explored and studied in order to clarify its mechanism. TCM has
      abundant clinical experience in treating cerebral disease with medicine that
      enforces the kidney and promotes wit. However, there has been no research on
      treating diabetic cognitive impairment, which requires work to be done actively
      and TCM to be put into full play, in order to improve the treatment of diabetes
      and enhance living quality of patients.

PMID- 16571295
TI  - [Freedom under responsibility].

PMID- 16571296
TI  - [Obesity: prevention and treatment. The Danish Society of Obesity Research].

PMID- 16571297
TI  - [General practice research in Denmark: status and organization. The Danish
      Society of General Practice].

PMID- 16571298
TI  - [Hypothermia protects the brain after heart arrest. The Danish Society of
      Anesthesiology and Intensive Medicine].

PMID- 16571299
TI  - [Occupational reproduction epidemiology on the basis of the Danish National Birth
      Cohort. The Danish Society of Occupational Medicine].

PMID- 16571300
TI  - [New types of dopaminergic treatment. The Danish Society of Movement Disorders].

PMID- 16571301
TI  - [The Danish registry for child and adolescent diabetes. The Danish Society of
      Child and Adolescent Diabetes].

PMID- 16571302
TI  - [Schizophrenia in children and adolescents. The Danish Society of Child and
      Adolescent Psychiatry].

PMID- 16571303
TI  - [Atrial fibrillation--towards non-inflammatory treatment? The Danish Society of
      Cardiology].

PMID- 16571304
TI  - [Dermatology--new therapeutic possibilities. The Danish Society of Dermatology].

PMID- 16571305
TI  - [Alcohol and evidence--about reading the literature. The Danish Society of
      Epidemiology].

PMID- 16571306
TI  - [Future incision?--epilepsy surgery. The Danish Society of Epilepsy].

PMID- 16571307
TI  - [Nobel Prize for the discovery of Helicobacter pylori. The Danish Society of
      Gastroenterology].

PMID- 16571308
TI  - [Orthogeriatrics in Denmark--now and in future. The Danish Society of
      Geriatrics].

PMID- 16571309
TI  - [Vaccine against human papillomavirus. The Danish Society of Gynecology and
      Obstetrics].

PMID- 16571310
TI  - [Hepatocellular carcinoma and other liver tumors. The Danish Society of
      Hepatology (DASL)].

PMID- 16571311
TI  - [Masked hypertension--a new and overlooked problem. The Danish Society of
      Hypertension].

PMID- 16571312
TI  - [Treatment of chronic hepatitis C. The Danish Society of Infection Medicine].

PMID- 16571313
TI  - [New treatment of ruptured aortic aneurysm. The Danish Society of Vascular
      Surgery].

PMID- 16571314
TI  - [Role of physician-coordinator at the emergency unit. The Danish Society of
      Disaster Medicine].

PMID- 16571315
TI  - [Visions for future organization of surgery. The Danish Society of Surgery].

PMID- 16571316
TI  - [Biobanks--a resource for the future. The Danish Society of Clinical
      Biochemistry].

PMID- 16571317
TI  - [Malnutrition in hospitals--what do we do? The Danish Society of Clinical
      Nutrition].

PMID- 16571318
TI  - [Examinations of the autonomic nervous system. The Danish Society of Clinical
      Physiology and Nuclear Medicine].

PMID- 16571319
TI  - [New beta-lactamases in enterobacteriaceae. The Danish Society of Clinical
      Microbiology].

PMID- 16571320
TI  - [Trastuzumab improves adjuvant therapy. The Danish Society of Clinical Oncology].

PMID- 16571321
TI  - [We are still waiting. The Danish Society for Health Sector Quality].

PMID- 16571322
TI  - [Omalizumab and asthma--ultrasonically guided needle biopsy. The Danish Society
      of Pulmonary Medicine].

PMID- 16571323
TI  - [Molecular karyotyping. The Danish Society of Molecular Genetics].

PMID- 16571324
TI  - [Hemicraniectomy in malignant media infarction. The Danish Society of
      Neurosurgery].

PMID- 16571325
TI  - [Sleep medicine--from amusement to science. The Danish Society of Neurology].

PMID- 16571326
TI  - [Age-related macular degeneration. The Danish Society of Ophthalmology].

PMID- 16571327
TI  - [Minimally invasive surgery in total hip alloplasty. The Danish Society of
      Orthopedic Surgery].

PMID- 16571328
TI  - [Universal neonatal hearing screening. The Danish Society of Otolaryngology, Head
      and Neck Surgery].

PMID- 16571329
TI  - [The role of pathology in individualized targetted cancer treatment. The Danish
      Society of Pathologic Anatomy and Cytology].

PMID- 16571330
TI  - [64 slice-computer tomography or coronary arteriography. The Danish Society of
      Radiology].

PMID- 16571331
TI  - [Progress in rheumatology. The Danish Society of Rheumatology].

PMID- 16571332
TI  - [Evidence in wound healing. The Danish Society of Wound Healing].

PMID- 16571333
TI  - [Poverty, health and development. The Danish Society of Tropical
      Medicine&International Health].

PMID- 16571334
TI  - [Prostatic cancer 2006--status and new challenges. The Danish Society of
      Urology].

PMID- 16571340
TI  - [The obligation to inform contra professional secrecy. Where is the boundary?].

PMID- 16571344
TI  - [The physician's oath should prohibit misuse of medical science].

PMID- 16571351
TI  - SB-649915, a novel, potent 5-HT1A and 5-HT1B autoreceptor antagonist and 5-HT re
      uptake inhibitor in native tissue.
AB  - An increase in brain 5-HT levels is thought to be the key mechanism of action
      which results in an antidepressant response. It has been proven that selective
      serotonin re-uptake inhibitors are effective antidepressants but the delay to
      therapeutic onset of these agents is thought to be due to the time required for 5
      HT1A, and possibly 5-HT1B, autoreceptor desensitisation. Therefore an agent
      incorporating 5-HT re-uptake inhibition coupled with 5-HT1A and/or 5-HT1B
      autoreceptor antagonism may provide a fast acting clinical agent. The current
      studies describe the in vitro profile of SB-649915 (6-[(1-{2-[(2-methylquinolin-5
      yl)oxy]ethyl}piperidin-4-yl)methyl]-2H-1,4-benzoxazin-3(4H)-one), a novel
      compound which has high affinity for human recombinant 5-HT1A, 5-HT1B and 5-HT1D
      receptors (pKi values of 8.6, 8.0, 8.8, respectively) and the human recombinant 5
      HT transporter (pKi value of 9.3). SB-649915 also displays high affinity for rat,
      guinea pig, mouse and marmoset native tissue 5-HT1A, 5-HT1B and 5-HT1D receptors
      and rat native tissue 5-HT transporters (pKi values>or=7.5). In functional
      [35S]GTPgammaS binding studies, SB-649915 (up to 1 microM) does not display
      intrinsic activity in HEK293 cells expressing human recombinant 5-HT1A receptors
      but acts as a partial agonist at human recombinant 5-HT1B and 5-HT1D receptors
      with intrinsic activity values of 0.3 and 0.7, respectively, as compared to the
      full agonist 5-HT. From Schild analysis, SB-649915 caused a concentration
      dependent, rightward shift of 5-HT-induced stimulation of basal [35S]GTPgammaS
      binding in cells expressing human recombinant 5-HT1A or 5-HT1B receptors to yield
      pA2 values of 9.0 and 7.9, respectively. In electrophysiological studies in rat
      dorsal raphe nucleus, SB-649915 did not affect the cell firing rate up to 1
      microM but attenuated (+)8-hydroxy-2-(di-n-propylamino) tetralin-induced
      inhibition of cell firing with an apparent pKb value of 9.5. SB-649915 (1 microM)
      significantly attenuated exogenous 5-HT-induced inhibition of electrically
      stimulated [3H]5-HT release from guinea pig cortex. In studies designed to
      enhance endogenous 5-HT levels, and therefore increase tone at 5-HT1B
      autoreceptors, SB-649915 significantly potentiated [3H]5-HT release at 100 and
      1000 nM. In LLCPK cells expressing human recombinant 5-HT transporters and in rat
      cortical synaptosomes, SB-649915 inhibited [3H]5-HT re-uptake with pIC50 values
      of 7.9 and 9.7, respectively. In summary, SB-649915 is a novel, potent 5-HT1A/1B
      autoreceptor antagonist and 5-HT re-uptake inhibitor in native tissue systems and
      represents a novel mechanism that could offer fast acting antidepressant action.

PMID- 16571353
TI  - Schistosoma mansoni: a diagnostic approach to detect acute schistosomiasis
      infection in a murine model by PCR.
AB  - Schistosomiasis represents an increasing problem in non-endemic areas, due to the
      growing number of immigrants and to tourists contracting this disease in "off-the
      beaten-track" tourism. Acute schistosomiasis is not diagnosed early due to the
      lack of diagnostic tools that are sufficiently sensitive enough to detect the
      parasite during the first weeks of infection. We have developed a diagnostic
      approach based on the detection of parasite DNA by polymerase chain reaction
      (PCR) in urine, comparing the performance of this new approach with the two
      currently used schistosomiasis diagnostic tools (Kato-Katz and ELISA) and the PCR
      in stool samples. This comparison was done in a Schistosoma mansoni murine
      experimental model, which permits follow up of the parasite from the acute to the
      chronic stage of infection. Our results suggest that this new PCR-based approach
      could be useful for the detection of acute schistosomiasis in easy-to-handle
      clinical samples such the urine.

PMID- 16571354
TI  - Dechlorination of chlorophenols by magnesium-silver bimetallic system.
AB  - More than 85% of 10 mg L(-1) of pentachlorophenol (PCP) was removed by
      magnesium/silver (206/1.47 mM) bimetal system in the presence of acetic acid.
      Dechlorination was found to be sequential and phenol was identified as the
      ultimate hydrocarbon skeleton along with some accumulation of tetra-, tri-, and
      dichlorophenols. The dechlorination reaction was found to follow second-order
      kinetics. Lower PCP removal efficiency (35%) was observed when the reaction was
      carried out in the absence of acid using Mg(0)/Ag system. When the reaction was
      conducted using Mg(0) alone in the presence of acid, substantial sorption of PCP
      occurred with very low efficiency of PCP dechlorination. Dechlorination studies
      on 10 mg L(-1) initial concentrations of 2,3,4,6-tetrachlorophenol (2,3,4,6-TeCP)
      and 2,4,5-trichlorophenol (2,4,5-TCP), under identical conditions as to PCP,
      revealed that dechlorination efficiency and reaction rate constants decrease with
      decreasing number of chlorine atoms on the target compound. A correlation
      (R(2)>0.9) between the dechlorination rate constants and E(LUMO) for
      chlorophenols was obtained.

PMID- 16571352
TI  - Unique and complimentary activities of the Gli transcription factors in Hedgehog
      signaling.
AB  - The Gli family of transcription factors (Gli1, 2 and 3) mediate the Hedgehog
      morphogenetic signal by regulating the expression of downstream target genes.
      Aberrations in Hedgehog signaling seriously affect vertebrate development.
      Postnatally, Hedgehog signaling has been postulated to play a pivotal role in
      healing and repair processes and inappropriate pathway activation has been
      implicated in several types of cancers. To better understand both the upstream
      regulation of the Gli transcription factors, as well as their unique and
      combinatorial roles in regulating the expression of Hedgehog target genes, we
      have characterized embryonic fibroblasts (MEFs) from Gli mutant mice. Stimulation
      of wild-type MEFs by Sonic Hedgehog (Shh) peptide elicited unique profiles of
      induction of Hedgehog target genes Gli1, Ptc1, and Hip1. Gli2 loss-of-function
      was associated with diminished Shh-induced target gene expression, while Gli3
      loss-of-function was associated with increased basal and Shh-induced target gene
      expression. The loss of Gli1 alone had no effect on target gene induction but did
      diminish Shh-induced target gene expression when combined with the loss of Gli2
      or Gli3. Additionally, overexpression of Gli1 induced target gene expression in
      Gli2(-/-)3(-/-) MEFs, while Shh stimulation did not. Using MEFs expressing only
      Gli2 or Gli3, we found that both cyclopamine and the PKA activator forskolin
      inhibited target gene induction mediated by Gli2 and Gli3. These results
      demonstrate that Gli2 and Gli3 share common regulatory mechanisms and modulate
      Hedgehog target gene expression directly and independently while also regulating
      Gli1 expression, which in specific contexts, coordinately contributes to target
      gene activation.

PMID- 16571356
TI  - Surface orientation, modulation frequency and the detection and perception of
      depth defined by binocular disparity and motion parallax.
AB  - Binocular disparity and motion parallax provide information about the spatial
      structure and layout of the world. Descriptive similarities between the two cues
      have often been noted which have been taken as evidence of a close relationship
      between them. Here, we report two experiments which investigate the effect of
      surface orientation and modulation frequency on (i) a threshold detection task
      and (ii) a supra-threshold depth-matching task using sinusoidally corrugated
      surfaces defined by binocular disparity or motion parallax. For low frequency
      corrugations, an orientation anisotropy was observed in both domains, with
      sensitivity decreasing as surface orientation was varied from horizontal to
      vertical. In the depth-matching task, for surfaces defined by binocular disparity
      the greatest depth was seen for oblique orientations. For surfaces defined by
      motion parallax, perceived depth was found to increase as surface orientation was
      varied from horizontal to vertical. In neither case was perceived depth for supra
      threshold surfaces related to threshold performance in any simple manner. These
      results reveal clear differences between the perception of depth from binocular
      disparity or motion parallax, and between perception at threshold and supra
      threshold levels of performance.

PMID- 16571355
TI  - Motor activation in SPG4-linked hereditary spastic paraplegia.
AB  - OBJECTIVE: The aim of this study was to investigate the extent of motor cortical
      functional reorganisation in patients with SPG4-linked hereditary spastic
      paraplegia by exploring cortical motor activation related to movements of
      clinically affected (lower) and unaffected (upper) limbs. METHODS: Thirteen
      patients and 13 normal controls matched for age, gender and handedness underwent
      O15-labelled water positron emission tomography during (1) right ankle flexion
      extension, (2) right shoulder flexion-extension and (3) rest. Within-group
      comparisons of movement vs. rest (simple main effects) and between-group
      comparisons of movement vs. rest (group x behavioural state interaction) were
      performed using a random effects approach and statistical parametric mapping
      (SPM99). RESULTS: Patterns of motor activation were generally comparable between
      groups during both tasks, although patients had a tendency towards more
      widespread activation in sensorimotor cortical and cerebellar regions.
      Statistically significant differences were restricted to the ankle movement
      response, however, where patients showed significantly increased regional
      cerebral blood flow in the right and left primary motor cortices, the
      supplementary motor areas and the right premotor cortex compared to controls.
      CONCLUSIONS: Motor cortical reorganisation may explain this result, but as no
      significant differences were recognised in the motor response of the unaffected
      limb, differences in functional demands should also be considered.

PMID- 16571357
TI  - Visual resolution with retinal implants estimated from recordings in cat visual
      cortex.
AB  - We investigated cortical responses to electrical stimulation of the retina using
      epi- and sub-retinal electrodes of 20-100 microm diameter. Temporal and spatial
      resolutions were assessed by recordings from the visual cortex with arrays of
      microelectrodes and optical imaging. The estimated resolutions were approximately
      40 ms and approximately 1 degrees of visual angle. This temporal resolution of 25
      frames per second and spatial resolution of about 0.8 cm at about 1m and
      correspondingly 8 cm at 10 m distance seems sufficient for useful object
      recognition and visuo-motor behavior in many in- and out-door situations of daily
      life.

PMID- 16571358
TI  - Monofluorinated analogues of polychlorinated biphenyls (F-PCBs): synthesis using
      the Suzuki-coupling, characterization, specific properties and intended use.
AB  - An improved method, a palladium-catalyzed cross-coupling reaction the so-called
      Suzuki-coupling, was used to synthesize 19 monofluorinated analogues (F-PCBs) of
      polychlorinated biphenyls (PCBs), including analogues of PCBs 28, 52 and 81. The
      coupling of chlorinated and/or fluorinated isomers of aryl boronic acids with
      bromo- and/or iodobenzenes gave the desired F-PCB congeners in good to excellent
      yields. The self-coupling product of the aryl boronic acids was the major
      impurity, but this limitation could be minimized. The influence of ortho
      substitution by chlorine on the reaction time was studied in detail. The F-PCBs
      were characterized by means of 1H and 19F NMR and mass spectrometry (MS). F-PCBs
      show remarkably similar characteristics in many aspects to those of the
      corresponding non-fluorinated parent PCBs. Since fluorine is generally resistant
      to degradation, once incorporated into a substrate it functions as an indelible
      label that can be used to monitor structures and dynamics. F-PCBs may prove their
      usefulness as markers and tracers in mechanistic and toxicological studies. The
      aim of further research will be to test the suitability of fluorine as a
      sensitive probe in a broad range of applications, including synthesis,
      analytical, mechanistic and toxicological studies.

PMID- 16571359
TI  - Joint anti-estrogenic effects of PCP and TCDD in primary cultures of juvenile
      goldfish hepatocytes using vitellogenin as a biomarker.
AB  - This work evaluated the joint anti-estrogenic effects of pentachlorophenol (PCP)
      and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) against 17beta-estradiol (E2) in
      juvenile goldfish (Carassius auratus) hepatocyte cultures. The level of
      vitellogenin (VTG) as a biomarker was determined by exposing hepatocytes to
      individual E2, PCP and TCDD, as well as to E2 in the presence of PCP, TCDD or
      their mixtures of various concentrations. PCP and TCDD did not exhibit
      estrogenicity. Both chemicals reduced the estrogenicity of E2, indicating the
      anti-estrogenic effects of PCP and TCDD. Their anti-estrogenic EC(50) values were
      calculated. The joint anti-estrogenic effects against E2 increased with
      increasing the PCP-to-TCDD ratio of mixture. Marking's indices were <0,
      suggesting an antagonism in anti-estrogenic effects between PCP and TCDD. The
      anti-estrogenic effects of PCP appeared to result primarily from the competitive
      binding to estrogen receptor. While TCDD may undergo an indirect binding process
      for its anti-estrogenic effects, the accurate mechanisms remain to be understood.
      The observed antagonism in anti-estrogenic effects resulted apparently from the
      mutual inhibition by PCP and TCDD.

PMID- 16571360
TI  - Influence of mass transfer resistance on overall nitrate removal rate in upflow
      sludge bed reactors.
AB  - A kinetic model with intrinsic reaction kinetics and a simplified model with
      apparent reaction kinetics for denitrification in upflow sludge bed (USB)
      reactors were proposed. USB-reactor performance data with and without sludge
      wasting were also obtained for model verification. An independent batch study
      showed that the apparent kinetic constants k' did not differ from the intrinsic k
      but the apparent Ks' was significantly larger than the intrinsic Ks suggesting
      that the intra-granule mass transfer resistance can be modeled by changes in Ks.
      Calculations of the overall effectiveness factor, Thiele modulus, and Biot number
      combined with parametric sensitivity analysis showed that the influence of
      internal mass transfer resistance on the overall nitrate removal rate in USB
      reactors is more significant than the external mass transfer resistance. The
      simulated residual nitrate concentrations using the simplified model were in good
      agreement with the experimental data; the simulated results using the simplified
      model were also close to those using the kinetic model. Accordingly, the
      simplified model adequately described the overall nitrate removal rate and can be
      used for process design.

PMID- 16571361
TI  - Photocatalytic oxidation of triclosan.
AB  - In the spring of 2003, there was an outbreak of the severe respiratory syndrome
      (SARS) in Hong Kong. Health concerns have thus triggered an increased and
      predominant use of various types of household cleansing agents such as triclosan
      (5-chloro-2-(2,4-dichlorophenoxy)phenol). However, it has been reported recently
      that triclosan could be photochemically converted to toxic 2,8-dichlorodibenzo-p
      dioxin (2,8-Cl(2)DD) in the environment. It is therefore necessary to develop
      environmentally friendly methods for the treatment of triclosan. To this end,
      photocatalytic degradation of triclosan in aqueous solution was conducted using
      TiO(2) (Degussa P25) under irradiation of UV light (lambda < 365 nm). It was
      found that triclosan could be degraded by this approach. Hydrogen peroxide was
      added to enhance the degradation process, and the optimal initial hydrogen
      peroxide concentration for triclosan degradation was 0.005% (w/v). Product
      identification indicated that triclosan oxidation occurred at its phenol moiety
      and yielded quinone and hydroquinone intermediates. The formation of a
      dichlorophenol intermediate in triclosan degradation suggested bond-breaking of
      the ether linkage occurred during the process. Moreover, no chlorinated dibenzo-p
      dioxin congener was detected. These findings confirm that the photocatalytic
      degradation of triclosan is an environmentally friendly process.

PMID- 16571362
TI  - Survismeter--type I and II for surface tension, viscosity measurements of liquids
      for academic, and research and development studies.
AB  - For centuries surface tension (gamma) and viscosity (eta) data have been measured
      with individual instruments consuming much time and materials. Thus the two
      different types of survismeters have been designed and made of borosil glass
      material for surface tension and viscosity data to rationalize frictional and
      cohesive forces, respectively. Friccohesity (sigma (sm(-1), second per meter)) is
      derived from Fric of frictional and cohesity of cohesive forces of the liquid
      respectively, and denoted by rational coefficient a eta/gamma (sigma). The values
      of the friccohesity are correlated to the dipole moment of liquids and their plot
      gives a standard calibration curve along with an equation of the curve with
      definite values of the coefficients, the friccohesity values are put on the
      calibration curve to retrieve the dipole moment values. Here, the sigma values
      for each of dimethylformamide, dimethylsulfoxide and acetronitrile solvents along
      with their 0.05, 0.10 and 0.20 mol kg(-1) aqueous solutions, respectively, were
      determined at 293.15K and plotted against their dipole moment values for standard
      calibration curve. The range of the dipole moment values for calibration curve is
      pre-decided and the sigma values for homogenous solutions of compositions below
      their saturation point can be measured with +/-1 x 10(-5)sm(-1).

PMID- 16571363
TI  - Molecular mechanism of mitochondrial membrane fusion.
AB  - Mitochondrial fusion requires coordinated fusion of the outer and inner
      membranes. This process leads to exchange of contents, controls the shape of
      mitochondria, and is important for mitochondrial function. Two types of
      mitochondrial GTPases are essential for mitochondrial fusion. On the outer
      membrane, the fuzzy onions/mitofusin proteins form complexes in trans that
      mediate homotypic physical interactions between adjacent mitochondria and are
      likely directly involved in outer membrane fusion. Associated with the inner
      membrane, the OPA1 dynamin-family GTPase maintains membrane structure and is a
      good candidate for mediating inner membrane fusion. In yeast, Ugo1p binds to both
      of these GTPases to form a fusion complex, although a related protein has yet to
      be found in mammals. An understanding of the molecular mechanism of fusion may
      have implications for Charcot-Marie-Tooth subtype 2A and autosomal dominant optic
      atrophy, neurodegenerative diseases caused by mutations in Mfn2 and OPA1.

PMID- 16571364
TI  - The extent to which students' perceptions of faculties' teaching strategies,
      students' context, and perceptions of learner empowerment predict perceptions of
      autonomy in BSN students.
AB  - This descriptive correlational study examined the extent to which students'
      perceptions of faculties' teaching strategies, students' context, and perceptions
      of learner empowerment predicted perceptions of autonomy in senior female generic
      baccalaureate degree (BSN) students in Northeastern Pennsylvania, USA. Dunkin and
      Biddle's Model for Classroom Teaching (1974) provided the theoretical framework
      for this study. The sample of 198 female senior nursing students was drawn from
      32 nursing programs accredited by the National League for Nursing Accrediting
      Commission [National League for Nursing Accrediting Commission (NLNAC) 2002.
      Directory of accredited programs. Retrieved July 16, 2002 from,
      http://www.nlnac.org/]. Three separate instruments were used in this study: (1)
      Learner Empowerment Measure [Frymier, A.B., Shulman, G.M., Houser, M., 1996. The
      development of a learner empowerment measure. Communication Education, 45, 181
      199.]; (2) Autonomy, Caring Perspective [Boughn, S., 1995. An instrument for
      measuring autonomy related attitudes and behaviors in women nursing students.
      Journal of Nursing Education, 34, 106-113.] and (3) an investigator designed
      student demographic data questionnaire. Data were analyzed using stepwise
      multiple linear regression to estimate path coefficients. Inspection of the
      findings revealed that there was a significant direct effect (t = 4.299, p <
      .001) between perceptions of learner empowerment and perceptions of autonomy. Age
      was also found to have a statistically significant direct effect on perceptions
      of autonomy (t = 2.652, p = .009). The findings from this study support a link
      between learner empowerment, stated as a priority in nursing education, and
      autonomy identified as a priority in practice.

PMID- 16571365
TI  - Managing the aggressive and violent patient in the psychiatric emergency.
AB  - Throughout history most societies have assumed a link between mental disorders
      and violence. Although the majority of users of mental health services are not
      violent, it is clear that a small yet significant minority are violent in
      inpatient settings and in the community. The assessment of a violent patient may
      be very difficult due to the lack of a full medical and psychiatric history and
      the non-cooperativeness of the patient. Thus a full assessment is important for
      the early decisions that the clinician has to take in a very quick and effective
      way. The primary task and the short term outcome in a behavioral emergency is to
      act as soon as possible to stop the violence from escalating and to find the
      quickest way to keep the patient's agitation and violence under control with the
      maximum of safety for everybody and using the less severe effective intervention.
      The pharmacological treatment of acute, persisting and repetitive aggression is a
      serious problem for other patients and staff members. Currently, there is no
      medication approved by the Food and Drug Administration (FDA) for the treatment
      of aggression. Based on rather limited evidence, a wide variety of medications
      for the pharmacological treatment of acute aggression has been recommended:
      typical and atypical antipsychotics and benzodiazepines.

PMID- 16571366
TI  - Comments on "Association between Ala-9Val polymorphism of MnSOD gene and
      schizophrenia" by O. Akyol et al. Progress in Neuropsychopharmacology and
      Biological Psychiatry 29, 2005, 123-131.

PMID- 16571367
TI  - Using aripiprazole to resolve antipsychotic-induced symptomatic
      hyperprolactinemia: a pilot study.
AB  - OBJECTIVE: To assess the effectiveness of substituting aripiprazole for other
      antipsychotic drugs taken by stable schizophrenic patients suffering from
      antipsychotic agent-induced symptomatic hyperprolactinemia. METHODS: Seven female
      schizophrenic patients with symptomatic hyperprolactinemia (167.6+/-58.0
      microg/L) were recruited to take part in an 8-week open label trial of
      aripiprazole (10-20 mg/day) as a replacement for amisulpride or risperidone.
      Efficacy was assessed via PANSS and CGI-I scores. Serum prolactin levels were
      measured at baseline, week 4, and week 8. Data were collected from November, 2004
      to May, 2005. RESULTS: At the end of weeks 4, serum prolactin levels were
      normalized (8.8+/-5.5 microg/L) and hyperprolactinemic symptoms were resolved in
      all patients. However, aripiprazole treatment was discontinued within 6 weeks for
      2 of the 7 subjects due to aggravated auditory hallucinations. CONCLUSION:
      Results from this admittedly small-scale open-label study indicate that switching
      to aripiprazole may be useful for resolving antipsychotic-induced
      hyperprolactinemia and associated symptoms.

PMID- 16571368
TI  - Alcohol and violence: comparison of the psychosocial correlates of adolescent
      involvement in alcohol-related physical fighting versus other physical fighting.
AB  - This study examined the demographic and psychosocial correlates of alcohol
      related physical fighting and other physical fighting to determine if the
      predictors for aggressive behaviors are similar or different when alcohol is
      involved. Analyses were based on the National Longitudinal Study of Adolescent
      Health which is a nationally representative school based sample of adolescents in
      grades 7 through 12 (N=18,924). The current analyses were restricted to current
      drinkers who could be grouped into three categories of involvement in physical
      fights (n=8866): no fighting; fighting not related to alcohol use; fighting
      related to alcohol use. Regression models were computed using a backward
      elimination procedure. Overall, 38% of adolescent drinkers reported fighting,
      including 12% who reported alcohol-related fighting and 26% who reported other
      physical fighting. Non-Hispanic African-American adolescents were most likely to
      report other physical fighting (37.1%) but they were least likely to report
      alcohol-related fighting (8.2%). The correlates of alcohol-related fighting
      differed by age and race/ethnicity. Moreover, since the correlates of alcohol
      related fighting pertain mostly to the frequency and quantity of alcohol use and
      to having alcohol-related problems, prevention efforts that seek to reduce
      alcohol use or delay alcohol use initiation may also reduce alcohol-related
      fighting.

PMID- 16571369
TI  - Neuronal information coding by oscillation phase prediction error: implications
      for consciousness and control of voluntary function.
AB  - Neuronal oscillatory firing patterns are widely thought to serve as coincidence
      detectors, so as to synchronize information processing across brain regions. I
      hypothesize here that, instead, oscillatory function can be better understood by
      reversing conventional models and regarding oscillations slower than 30 Hz as
      background activity occurring in the absence of conscious or voluntary function.
      Action potentials occurring out of phase with the local population oscillation
      then emerge as information carriers, according to a prediction error mechanism
      that was first described in the drug abuse literature. Shannon information
      calculations show that coding by out-of-phase action potentials is far more
      efficient than are conventional synchronization models, and a simple calculation
      of the degree to which an action potential is out of phase correctly predicts the
      amount of information content. This model appears to account for a wide range of
      existing experimental observations of visual attention, voluntary motor function,
      and movement disorders. It also suggests an intuitively simple way of
      understanding consciousness, based upon a "self-observing" feedback mechanism of
      neocortical neurons firing out of phase. The hypothesis also suggests that the
      function of slow-wave sleep may be to re-entrain desynchronized oscillations.

PMID- 16571370
TI  - Diversity, structure, and expression of the gene for p26, a small heat shock
      protein from Artemia.
AB  - p26, a small heat shock protein, is thought to protect Artemia embryos from
      stress during encystment and diapause. Full-length p26 cDNAs were compared and
      used to determine phylogenetic relationships between several Artemia species. The
      alpha-crystallin domain of p26 was the most conserved region of the protein and
      p26 from each Artemia species contained characteristic amino-terminal WD/EPF and
      carboxy-terminal VPI motifs. Sequence conservation suggested the importance of
      p26 to oviparously developing Artemia embryos and indicated common functions for
      the protein during development and stress resistance, although as shown by
      modeling some species-specific p26 amino acid substitutions may have adaptive
      significance. The p26 gene obtained from A. franciscana exhibited a unique sHSP
      intron arrangement with an intron in the 5'-untranslated region. Computer
      assisted analysis revealed heat shock elements and other putative cis regulatory
      sequences but their role in gene regulation is unknown. In contrast to previous
      results for which Northern blots were analyzed, p26 gene expression was observed
      in ovoviviparous embryos by use of PCR-based methodology, but the p26 protein was
      not detected.

PMID- 16571371
TI  - Placebo effects in laser-evoked pain potentials.
AB  - Placebo treatment may affect multiple components of pain, including inhibition of
      nociceptive input, automatic or deliberative appraisal of pain, or cognitive
      judgments involved in pain reporting. If placebo analgesia is due in part to an
      attenuation of early nociceptive processing, then pain-evoked event-related
      potentials (ERPs) should be reduced with placebo. In this study, we tested for
      placebo effects in P2 laser-evoked potentials at midline scalp electrodes. We
      found that placebo treatment produced significant decreases in P2 amplitude, and
      that P2 placebo responses were large enough to reflect a meaningful difference in
      nociceptive processing. However, we also found evidence that the very robust
      placebo-induced decreases in reported pain are not solely explained by early
      reductions in P2. N2 amplitude was affected by neither placebo nor reduction of
      laser intensity. These results suggest that placebo treatment affects early
      nociceptive processing, but that another component of placebo effects in reported
      pain occurs later, either in evaluation of pain or cognitive judgments about pain
      reports.

PMID- 16571373
TI  - Functional magnetic resonance imaging studies of eye movements in first episode
      schizophrenia: smooth pursuit, visually guided saccades and the oculomotor
      delayed response task.
AB  - Schizophrenia patients show eye movement abnormalities that suggest dysfunction
      in neocortical control of the oculomotor system. Fifteen never-medicated, first
      episode schizophrenia patients and 24 matched healthy individuals performed eye
      movement tasks during functional magnetic resonance imaging studies. For both
      visually guided saccade and smooth pursuit paradigms, schizophrenia patients
      demonstrated reduced activation in sensorimotor areas supporting eye movement
      control, including the frontal eye fields, supplementary eye fields, and parietal
      and cingulate cortex. The same findings were observed for an oculomotor delayed
      response paradigm used to assess spatial working memory, during which
      schizophrenia patients also had reduced activity in dorsolateral prefrontal
      cortex. In contrast, only minimal group differences in activation were found
      during a manual motor task. These results suggest a system-level dysfunction of
      cortical sensorimotor regions supporting oculomotor function, as well as in areas
      of dorsolateral prefrontal cortex that support spatial working memory. These
      findings indicate that a generalized rather than localized pattern of neocortical
      dysfunction is present early in the course of schizophrenia and is related to
      deficits in the sensorimotor and cognitive control of eye movement activity.

PMID- 16571372
TI  - Postnatal manganese exposure attenuates cocaine-induced locomotor activity and
      reduces dopamine transporters in adult male rats.
AB  - In the present study, we examined whether exposing rats to manganese (Mn) during
      the preweanling period would affect basal or cocaine-induced locomotor activity
      in adulthood and reduce the number of striatal dopamine transporter binding
      sites. On postnatal day (PD) 1-21, rats were given oral supplements of vehicle or
      Mn chloride (250 or 750 microg/day). Striatal Mn and iron (Fe) accumulation as
      well as serum Fe levels were measured on PD 14, PD 21, and PD 90. Throughout the
      dosing period, rats were evaluated on standard measures of sensory and motor
      development. During adulthood, the basal and cocaine-induced locomotor activity
      of vehicle- and Mn-exposed rats was assessed using automated testing chambers.
      After completion of behavioral testing, striatal dopamine transporter binding
      sites were measured using [(3)H]GBR 12935. Results showed that early Mn exposure
      enhanced striatal Mn accumulation on PD 14 and PD 21, while depressing serum Fe
      levels on PD 21. Exposure to Mn on PD 1-21 did not affect striatal or serum Mn or
      Fe levels on PD 90. During the second postnatal week, Mn-exposed rat pups
      performed more poorly than controls on a negative geotaxis task, however basal
      motor activity of preweanling rat pups was not affected by Mn treatment. When
      tested in adulthood, basal locomotor activity of vehicle- and Mn-exposed rats
      also did not differ. In contrast, adult rats previously exposed to 750 microg/day
      Mn showed an enhanced locomotor response when challenged with 10 mg/kg cocaine. A
      different pattern of results occurred after treatment with a higher dose of the
      psychostimulant, because Mn-exposed rats showed an attenuated locomotor response
      when given 20 mg/kg cocaine. Importantly, Mn-exposed rats exhibited long-term
      reductions in striatal dopamine transporter binding sites. Considered together,
      these results indicate that postnatal Mn exposure has long-term behavioral and
      neurochemical effects that can persist into adulthood.

PMID- 16571374
TI  - Production of a recombinantly expressed laminin fragment by HEK293-EBNA cells
      cultured in suspension in a dialysis-based bioreactor.
AB  - Laminin 5 is a multifunctional extracellular matrix protein, which supports
      epithelial cell adhesion through multiple cell binding sites. For elaborate
      studies, a 35 kDa fragment localized at the C-terminal extremity of the molecule,
      the LG4/5 fragment was recombinantly expressed in mammalian HEK293-EBNA cells. As
      the production of the LG4/5 fragment by adherent cell monolayers was very low (<1
      microg/ml), we used the commercially available small scale bioreactor system
      miniPERM. The HEK293-EBNA transfectants were adapted to grow in suspension in
      defined medium containing low level of fetal calf serum and produced the
      recombinant LG4/5 protein with quality consistent with that produced in
      conventional static cell culture conditions. Cells grew without forming
      aggregates in the bioreactor and the resulting HEK293-EBNA-LG4/5 cell line was
      suitable for unlimited passages in the bioreactor. 2.5x10(5) cells/ml were
      cultured for 25 days to reach the maximal cell density of 1.6x10(7) cells/ml. The
      quantification of protein synthesis revealed that the highest level of 2.4 mg of
      recombinant LG4/5 protein was harvested when 10(7) transfected cells/ml were
      injected in the bioreactor and allowed to grow for 2 days. The mean daily
      recombinant LG4/5 fragment product yield of 1.2 mg of protein per minifermenter
      shows that cultivation of HEK293-EBNA transfectants in suspension is highly
      convenient for the production of recombinant laminin fragments.

PMID- 16571376
TI  - Mapping the intracellular fraction of water by varying the gradient pulse length
      in q-space diffusion MRI.
AB  - Finite gradient pulse lengths are traditionally considered a nuisance in q-space
      diffusion NMR and MRI, since the simple Fourier relation between the acquired
      signal and the displacement probability is invalidated. Increasing the value of
      the pulse length leads to an apparently smaller value of the estimated
      compartment size. We propose that q-space data at different gradient pulse
      lengths, but with the same effective diffusion time, can be used to identify and
      quantify components with free or restricted diffusion from multiexponential echo
      decay curves obtained on cellular systems. The method is demonstrated with
      experiments on excised human brain white matter and a series of model systems
      with well-defined free, restricted, and combined free and restricted diffusion
      behavior. Time-resolved diffusion MRI experiments are used to map the spatial
      distribution of the intracellular fraction in a yeast cell suspension during
      sedimentation, and observe the disappearance of this fraction after a heat
      treatment.

PMID- 16571377
TI  - Ultrasound assisted phase-transfer catalytic epoxidation of 1,7-octadiene - a
      kinetic study.
AB  - An ultrasound assisted phase-transfer catalyzed epoxidation of 1,7-octadiene is
      greatly enhanced by using a cocatalyst of phosphotungstic acid in the presence of
      hydrogen peroxide in an organic solvent/aqueous solution two-phase medium. An
      active intermediate of the catalyst (Q3PW12(O)nO40, where Q = R4N+) produced from
      the reaction of phosphotungstic acid, hydrogen peroxide, and Aliquat 336. A
      rational mechanism of epoxidation is proposed to account for the reaction from
      the experimental evidence. The organic-phase reactions, including two series
      reactions, are the rate-controlling steps to produce two products, viz., 1,2
      epoxy-7-octene and 1,2,7,8-diepoxyoctane. The kinetics of epoxidation, including
      the characteristics of the catalyst and the effect of the amount of cocatalyst,
      agitation speed, quaternary ammonium salts, amount of Aliquat 336, amount of
      hydrogen peroxide, amount of chloroform, pH value, organic solvents, and
      temperature on the conversion of 1,7-octadiene were investigated in detail. A
      kinetic model was built, from which a pseudo-first-order rate law is sufficient
      to describe the behavior of the reaction.

PMID- 16571378
TI  - Spatial-temporal dynamics of cavitation bubble clouds in 1.2 MHz focused
      ultrasound field.
AB  - Cavitation bubbles have been recognized as being essential to many applications
      of ultrasound. Temporal evolution and spatial distribution of cavitation bubble
      clouds induced by a focused ultrasound transducer of 1.2 MHz center frequency are
      investigated by high-speed photography. It is revealed that at a total acoustic
      power of 72 W the cavitation bubble cloud first emerges in the focal region where
      cavitation bubbles are observed to generate, grow, merge and collapse during the
      initial 600 micros. The bubble cloud then grows upward to the post-focal region,
      and finally becomes visible in the pre-focal region. The structure of the final
      bubble cloud is characterized by regional distribution of cavitation bubbles in
      the ultrasound field. The cavitation bubble cloud structure remains stable when
      the acoustic power is increased from 25 W to 107 W, but it changes to a more
      violent form when the acoustic power is further increased to 175 W.

PMID- 16571379
TI  - The medical and ethical aspects of photography in the sexual assault examination:
      why does it offend?
AB  - This paper reviews the literature in respect to the photo-colposcopic examination
      of anogenital injury in the sexually assaulted child, considered to be the 'gold
      standard' of examination, and how this compares with gross visualisation, still
      the standard procedure in adult examinations. It then examines the claim that,
      because the presence of injury does not provide a distinction between consensual
      and non-consensual intercourse in adults, photo-documentation is unnecessary
      medically and constitutes an invasive procedure which is ethically unacceptable.
      The paper questions whether the unwillingness of forensic physicians to extend
      photo-colposcopy to the examination of adult victims is related more to political
      and gender issues than to claims made on ethical and medical grounds, and
      concludes that any move to ban anogenital photography in adult forensic
      examinations (currently under consideration in the author's own jurisdiction)
      would possibly constitute an interference with independent clinical judgment and
      an incursion into the patient's right to evidence-based medicine.

PMID- 16571380
TI  - Histamine increases sphingosine kinase-1 expression and activity in the human
      arterial endothelial cell line EA.hy 926 by a PKC-alpha-dependent mechanism.
AB  - Sphingosine 1-phosphate (S1P) is a potent mitogenic signal generated from
      sphingosine by the action of sphingosine kinases (SKs). In this study, we show
      that in the human arterial endothelial cell line EA.hy 926 histamine induces a
      time-dependent upregulation of the SK-1 mRNA and protein expression which is
      followed by increased SK-1 activity. A similar upregulation of SK-1 is also
      observed with the direct protein kinase C activator 12-O-tetradecanoylphorbol-13
      acetate (TPA). In contrast, SK-2 activity is not affected by neither histamine
      nor TPA. The increased SK-1 protein expression is due to stimulated de novo
      synthesis since cycloheximide inhibited the delayed SK-1 protein upregulation.
      Moreover, the increased SK-1 mRNA expression results from an increased promoter
      activation by histamine and TPA. In mechanistic terms, the transcriptional
      upregulation of SK-1 is dependent on PKC and the extracellular signal-regulated
      protein kinase (ERK) cascade since staurosporine and the MEK inhibitor U0126
      abolish the TPA-induced SK-1 induction. Furthermore, the histamine effect is
      abolished by the H1-receptor antagonist diphenhydramine, but not by the H2
      receptor antagonist cimetidine. Parallel to the induction of SK-1, histamine and
      TPA stimulate an increased migration of endothelial cells, which is prevented by
      depletion of the SK-1 by small interfering RNA (siRNA). To appoint this specific
      cell response to a specific PKC isoenzyme, siRNA of PKC-alpha, -delta, and 
      epsilon were used to selectively downregulate the respective isoforms.
      Interestingly, only depletion of PKC-alpha leads to a complete loss of TPA- and
      histamine-triggered SK-1 induction and cell migration. In summary, these data
      show that PKC-alpha activation in endothelial cells by histamine-activated H1
      receptors, or by direct PKC activators leads to a sustained upregulation of the
      SK-1 protein expression and activity which, in turn, is critically involved in
      the mechanism of endothelial cell migration.

PMID- 16571375
TI  - Three-dimensional locations and boundaries of motor and premotor cortices as
      defined by functional brain imaging: a meta-analysis.
AB  - The mesial premotor cortex (pre-supplementary motor area and supplementary motor
      area proper), lateral premotor cortex (dorsal premotor cortex and ventral
      premotor cortex), and primary sensorimotor cortex (primary motor cortex and
      primary somatosensory cortex) have been identified as key cortical areas for
      sensorimotor function. However, the three-dimensional (3-D) anatomic boundaries
      between these regions remain unclear. In order to clarify the locations and
      boundaries for these six sensorimotor regions, we surveyed 126 articles
      describing pre-supplementary motor area, supplementary motor area proper, dorsal
      premotor cortex, ventral premotor cortex, primary motor cortex, and primary
      somatosensory cortex. Using strict inclusion criteria, we recorded the reported
      normalized stereotaxic coordinates (Talairach and Tournoux or MNI) from each
      experiment. We then computed the probability distributions describing the
      likelihood of activation, and characterized the shape, extent, and area of each
      sensorimotor region in 3-D. Additionally, we evaluated the nature of the overlap
      between the six sensorimotor regions. Using the findings from this meta-analysis,
      along with suggestions and guidelines of previous researchers, we developed the
      Human Motor Area Template (HMAT) that can be used for ROI analysis. HMAT is
      available through e-mail from the corresponding author.

PMID- 16571381
TI  - Plasma levels of ursodeoxycholic acid in black bears, Ursus americanus: seasonal
      changes.
AB  - To date, no other studies have examined the seasonal changes in circulating
      levels of various bile acids in the plasma of wild North American black bears,
      Ursus americanus. Using gas chromatography, bile acid concentrations were
      measured in plasma samples obtained during either early or late hibernation, and
      during summer active periods. Thus, specific compositional changes from
      individual animals were examined through a given year. Total bile acid
      concentrations in the plasma of these normal animals were found to range between
      0.2 and 3.1 micromol/L (0.9 +/- 0.2 micromol/L, mean +/- SEM). Cholic,
      ursodeoxycholic and chenodeoxycholic acids were the major bile acid species
      identified. Ursodeoxycholic acid represented 28.0 +/- 2.6% of the total bile acid
      pool. Deoxycholic and lithocholic acids were found only in small amounts. In
      addition, total bile acid concentrations were lower in plasma samples obtained
      during hibernation compared with those obtained during summer active periods (0.6
      +/- 0.1 and 1.2 +/- 0.4 micromol/L, respectively; p < 0.05). However, the
      relative proportion of ursodeoxycholic acid, was significantly greater in winter
      than in summer (31.5 +/- 3.2% and 22.2 +/- 4.5%, p < 0.05). Finally, taurine
      conjugated bile acids were the predominant species in bear plasma, accounting for
      >67% of the total bile acids. These data demonstrate that ursodeoxycholic acid is
      a major bile acid in black bear plasma, mostly conjugated with taurine. Further,
      the finding of seasonal variation in plasma bile acid composition provides
      evidence to support the possible role that ursodeoxycholic acid may play in
      cellular protection in hibernating black bears.

PMID- 16571383
TI  - Sex and age effects on outcomes of total hip arthroplasty after inpatient
      rehabilitation.
AB  - OBJECTIVE: To retrospectively examine the effects of sex and age on the inpatient
      rehabilitation outcomes of patients after total hip arthroplasty (THA). DESIGN:
      Exploratory, retrospective study. SETTING: A university-affiliated rehabilitation
      hospital. PARTICIPANTS: Male and female THA patients (N=332) were stratified into
      age brackets (<65y, 65-84y, >or=85y). All patients completed interdisciplinary
      inpatient rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Length of stay (LOS), FIM instrument scores, FIM efficiency (FIM/LOS), hospital
      costs, and discharge disposition location were collected by chart review.
      RESULTS: Regardless of age, women had lower FIM scores at admission and discharge
      than men (P<.05). FIM efficiency was 22% to 53% lower for women in primary THA
      and 16% to 85% lower in revision THA than men (P=.001). Women accrued higher
      total hospital charges than men (13,099 dollars vs 11,141 dollars; P<.05), and
      were discharged home less frequently than men (84.4% vs 90.9%; P<.05). Admission
      FIM scores were 10.6% and 8.9% lower and discharge FIM scores were 7.3% and 9.2%
      lower in patients 85 years or older than those less than 65 or 65 to 84 years
      (P<.01). FIM efficiency was 25% to 38% higher in patients less than 85 years than
      those 85 years and older (P=.015), and 37% higher in men than women (P=.001).
      Patients 85 years and older were discharged less frequently to home than patients
      less than 85 years (P<.05). CONCLUSIONS: All patients made functional improvement
      after inpatient rehabilitation, but women and patients 85 years and older had
      longer LOS and lower FIM efficiency, incurred greater hospital charges, and were
      less likely to be discharged to home than men and younger counterparts.

PMID- 16571382
TI  - Long-term risedronate treatment normalizes mineralization and continues to
      preserve trabecular architecture: sequential triple biopsy studies with micro
      computed tomography.
AB  - The objective of the study was to assess the time course of changes in bone
      mineralization and architecture using sequential triple biopsies from women with
      postmenopausal osteoporosis (PMO) who received long-term treatment with
      risedronate. Transiliac biopsies were obtained from the same subjects (n = 7) at
      baseline and after 3 and 5 years of treatment with 5 mg daily risedronate.
      Mineralization was measured using 3-dimensional (3D) micro-computed tomography
      (CT) with synchrotron radiation and was compared to levels in healthy
      premenopausal women (n = 12). Compared to the untreated PMO women at baseline,
      the premenopausal women had higher average mineralization (Avg-MIN) and peak
      mineralization (Peak-MIN) by 5.8% (P = 0.003) and 8.0% (P = 0.003), respectively,
      and lower ratio of low to high-mineralized bone volume (BMR-V) and surface area
      (BMR-S) by 73.3% (P = 0.005) and 61.7% (P = 0.003), respectively. Relative to
      baseline, 3 years of risedronate treatment significantly increased Avg-MIN (4.9
      +/- 1.1%, P = 0.016) and Peak-MIN (6.2 +/- 1.5%, P = 0.016), and significantly
      decreased BMR-V (-68.4 +/- 7.3%, P = 0.016) and BMR-S (-50.2 +/- 5.7%, P = 0.016)
      in the PMO women. The changes were maintained at the same level when treatment
      was continued up to 5 years. These results are consistent with the significant
      reduction of turnover observed after 3 years of treatment and which was similarly
      maintained through 5 years of treatment. Risedronate restored the degree of
      mineralization and the ratios of low- to high-mineralized bone to premenopausal
      levels after 3 years of treatment, suggesting that treatment reduced bone
      turnover in PMO women to healthy premenopausal levels. Conventional micro-CT
      analysis further demonstrated that bone volume (BV/TV) and trabecular
      architecture did not change from baseline up to 5 years of treatment, suggesting
      that risedronate provided long-term preservation of trabecular architecture in
      the PMO women. Overall, risedronate provided sustained benefits on mineralization
      and architecture, two key determinants of bone strength, over 5 years lending
      support for its long-term efficacy in fracture risk reduction.

PMID- 16571385
TI  - Rapid vascular adaptations to training and detraining in persons with spinal cord
      injury.
AB  - OBJECTIVE: To assess the time course of arterial adaptations during 6 weeks of
      functional electric stimulation (FES) training and 6 weeks of detraining in
      subjects with spinal cord injury (SCI). DESIGN: Intervention study (before-after
      trial). SETTING: University medical center. PARTICIPANTS: Volunteer sample of 9
      subjects with SCI. INTERVENTIONS: Six weeks of twice weekly FES cycling and 6
      weeks of detraining. MAIN OUTCOME MEASURES: Vascular characteristics were
      measured by plethysmography (baseline and peak blood flow of the thigh) and echo
      Doppler (diameter of the femoral artery and flow-mediated dilation [FMD]).
      RESULTS: After 2 weeks of FES training, arterial characteristics changed
      significantly; there was an increase in baseline and peak blood flow, an increase
      in femoral artery diameter, and a decrease in FMD of the femoral artery.
      Detraining reversed baseline and peak thigh blood flow, vascular resistance, and
      femoral diameter toward pretraining values within 1 week. However, detraining did
      not restore the FMD of the femoral artery, even after 6 weeks. CONCLUSIONS: Two
      weeks of hybrid FES training (4 exercise bouts) is sufficient to improve peak leg
      blood flow and arterial diameter, and to normalize FMD. In addition, detraining
      results in rapidly reversed vascular characteristics within 1 week.

PMID- 16571386
TI  - Oxygen consumption during machine-assisted and unassisted walking: a pilot study
      in hemiplegic and healthy humans.
AB  - OBJECTIVE: To determine whether a gait-training (GT) machine influenced walking
      time duration and oxygen consumption in hemiplegic patients. DESIGN: Repeated
      measures with comparison of 2 groups. SETTING: Physiology laboratories in a
      rehabilitation hospital. PARTICIPANTS: Seven patients with stroke-related
      hemiplegia (2 men, 5 women; age, 46+/-11y; time since stroke, 12+/-9wk) and 7
      healthy subjects (3 men, 4 women; age, 30+/-7y). INTERVENTIONS: Floor walking
      (FW) and GT-assisted walking with and without 50% body-weight support (BWS). MAIN
      OUTCOME MEASURES: Walking time duration, oxygen consumption (Vo(2)), minute
      ventilation (V(E)), and heart rate. RESULTS: When the condition effect was
      analyzed independently from the group, mean Vo(2) was higher during FW than
      during the GT tests (post hoc analysis: FW vs GT, P=.017; FW vs GT+BWS, P<.002).
      When the groups were compared independently of the condition, the group with
      hemiplegia had a significantly shorter walking time duration (analysis of
      variance [ANOVA], P<.001) and a significantly higher Vo(2) as a percentage of
      baseline (ANOVA, P=.03), compared with the controls. Walking time duration was
      influenced by walking condition (ANOVA, P<.001; post hoc analysis: FW vs GT,
      P<.001; FW vs GT+BWS, P<.001). Ve was influenced by walking condition (ANOVA,
      P=.043; not significant in the post hoc analysis) and was higher in the group
      with hemiplegia (ANOVA, P=.02). Heart rate was not influenced by walking
      condition (P=.11). A group effect was found with heart rate in cycles per minute
      (P=.035) but not as a percentage of baseline. No interaction was found between
      the ANOVA group-effect factor and the ANOVA walking-condition effect factor.
      CONCLUSIONS: Compared with FW, GT assistance increased walking time duration and
      reduced Vo(2) in patients with severe hemiplegia.

PMID- 16571384
TI  - Expiratory muscle strength training in persons with multiple sclerosis having
      mild to moderate disability: effect on maximal expiratory pressure, pulmonary
      function, and maximal voluntary cough.
AB  - OBJECTIVE: To determine the effect of expiratory muscle strength training (EMST)
      on maximal expiratory strength, pulmonary function, and maximal voluntary cough
      in persons with multiple sclerosis (MS) having mild to moderate disability.
      DESIGN: Before-after trial. SETTING: Assessments were completed in the privacy of
      the subject's home or exercise physiology laboratory. PARTICIPANTS: Seventeen
      persons with MS were age- and sex-matched to 14 healthy controls. INTERVENTION:
      Eight weeks of EMST and 4 weeks of detraining. MAIN OUTCOME MEASURES: Maximal
      respiratory pressures, pulmonary function, and maximal voluntary cough were
      assessed 3 times (pretraining, posttraining, detraining). Maximal expiratory
      pressure (MEP) was assessed weekly and training intensity adjusted based on the
      new measurement. RESULTS: Subjects with MS had lower MEP, decreased pulmonary
      function, and weaker maximal voluntary cough at each assessment. EMST increased
      MEP and peak expiratory flow. However, improvement in maximal voluntary cough
      only occurred in subjects with a moderate level of disability when the MS group
      was subdivided into mild and moderate disability levels based on the Expanded
      Disability Status Scale. CONCLUSIONS: EMST is a viable tool to enhance the
      strength of the respiratory muscles. However, further work is needed to determine
      the best parameters to assess change in cough following EMST.

PMID- 16571387
TI  - Bilateral sensorimotor abnormalities in unilateral lateral epicondylalgia.
AB  - OBJECTIVE: To evaluate impairments in motor function of the upper limb in
      unilateral lateral epicondylalgia. DESIGN: Assessor-blinded, case-controlled
      study. SETTING: University laboratory. PARTICIPANTS: Forty participants with
      lateral epicondylalgia and 40 age- and sex-matched controls were recruited from
      the general community. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Wrist posture adopted during a grip test, grip strength force, as well as upper
      limb reaction times and speed of movement. RESULTS: Participants with unilateral
      lateral epicondylalgia adopted wrist postures that were on average 11 degrees
      less extended, bilaterally, than controls (P<.000). This was paralleled by
      increased upper-limb reaction times and reduced speed of movement (mean
      differences, 2%-15%) in both affected and unaffected limbs. Pain-free grip
      strength was reduced on the involved side (mean difference, 170N; 95% confidence
      interval, 144-195N). CONCLUSIONS: Motor deficits may be modifiable through
      exercise and postural retraining. Although further work is required to evaluate
      the clinical efficacy of such an approach, health care practitioners have an
      emerging evidence base on which to base their management of lateral
      epicondylalgia.

PMID- 16571388
TI  - An observational electromyography study of the effect of trunk flexion in low
      velocity frontal whiplash-type impacts.
AB  - OBJECTIVE: To examine the effect of forward and lateral trunk flexion on the
      cervical electromyogram and head kinematic response to whiplash-type frontal
      impacts. DESIGN: Observational study of sled impacts. SETTING: Laboratory.
      PARTICIPANTS: Twenty healthy volunteers. INTERVENTION: Twenty volunteers were
      subjected to increasing low-velocity (<8km/h) frontal impacts of 4.4, 7.6, 10.3,
      and 13.3m/s(2) acceleration with trunk forward flexed by 45 degrees and laterally
      flexed to the right and left by 45 degrees . MAIN OUTCOME MEASURES: Bilateral
      electromyography of the sternocleidomastoids, trapezii, and splenii capitis and
      acceleration of the sled, torso, and head were recorded. RESULTS: With either
      direction of lateral trunk flexion at impact, the trapezii electromyographic
      activity increased with increasing acceleration (P<.05). With the trunk flexed to
      the left, the left trapezius generated 39% of its maximal voluntary contraction
      (MVC) electromyographic activity, while the right trapezius generated 31% of its
      MVC electromyographic activity. The left splenius (ipsilateral to leftward trunk
      flexion) generated 24% of its MVC electromyographic activity, with all other
      muscles generating 15% or less of this measure. With the trunk flexed to the
      right, the right trapezius generated 38% of its MVC electromyographic activity,
      while the left trapezius generated 32% of this value. Again, the ipsilateral (to
      trunk flexion) splenius capitis generated 27% of its MVC electromyographic
      activity, and all other muscles 11% or less of this measure. CONCLUSIONS: When
      subjects sit with trunk flexed out of neutral posture at the time of frontal
      impact, the cervical muscle response is low and unlikely to be injurious.

PMID- 16571390
TI  - The effect of visual biofeedback on the propulsion effectiveness of experienced
      wheelchair users.
AB  - OBJECTIVE: To determine the effect of visual feedback on the propulsion
      effectiveness of experienced manual wheelchair users. DESIGN: Controlled trial.
      SETTING: A motion analysis laboratory. PARTICIPANTS: A convenience sample of 16
      healthy men and 2 healthy women with T4-L2 traumatic paraplegia, a mean age of
      38+/-9 years, and a mean duration of manual wheelchair-based mobility of 14+/-8
      years. INTERVENTION: Propulsion was assessed as the subjects propelled an
      instrumented wheelchair (with and without visual biofeedback) on a custom-built
      dynamometer at propulsion intensities of .15 and .25W/kg for 10 minutes. MAIN
      OUTCOME MEASURES: The primary outcome variable was the fraction of effective
      force (FEF) (ie, the ratio of effective to total force) applied by the subject to
      the wheelchair's pushrim. Secondary variables included velocity, stroke
      frequency, and stroke angle. RESULTS: A 2-factor analysis of variance with
      repeated measurements was used to detect significant differences between the
      outcome variables. The FEF ratio was 73.9% without feedback and 72.5% with
      feedback at the lower-intensity level. Propulsion during the higher intensity
      condition both with and without feedback resulted in a statistically significant
      improvement in the FEF (73.9%-78.7% with no feedback, 72.5%-80.2% with feedback),
      compared with the lower-intensity level. Stroke angle increased from 84.3 degrees
      to 98.7 degrees and frequency decreased from 66 to 57.8 strokes/min with
      feedback. CONCLUSIONS: Visual biofeedback may have little utility in improving
      the force effectiveness of manual wheelchair propulsion in experienced wheelchair
      users. Experienced wheelchair users may have already optimized their stroke in a
      manner that balances energy expenditure with stroke efficiency. Other variables
      such as stroke length and frequency may be more amenable to visual biofeedback.

PMID- 16571389
TI  - Effect of different sitting postures on lung capacity, expiratory flow, and
      lumbar lordosis.
AB  - OBJECTIVE: To investigate the effect of sitting posture on lung capacity and
      expiratory flow (LC-EF) and lumbar lordosis. DESIGN: Repeated measures on 1 group
      of subjects in 4 postures. SETTING: Laboratory. PARTICIPANTS: Seventy able-bodied
      volunteers. INTERVENTIONS: Postures were assumed randomly: normal, with full
      ischial support and flat lumbar support; slumped, with the pelvis positioned in
      the middle of seat while leaning against the backrest; against the back part of
      the seat without ischial support (WO-BPS), with partially removed ischial support
      and an enhanced lumbar support; and standing. MAIN OUTCOME MEASURES: For LC-EF,
      forced vital capacity, maximum forced expiratory flow, forced expiratory volume
      in 1 second, and peak expiratory flow; and lumbar lordosis. RESULTS: All LC-EF
      measures in standing were significantly superior to those in slumped and normal
      sitting, and 4 measures were significantly higher than in WO-BPS. In slumped
      sitting, LC-EF significantly decreased from that in normal sitting. WO-BPS
      sitting significantly increased 4 of the LC-EF measures from those in the normal
      sitting. Lumbar lordosis was the highest in standing and progressively decreased
      in WO-BPS, normal, and slumped sitting. CONCLUSIONS: Slumped sitting
      significantly decreased LC-EF and lumbar lordosis. Because it increases the
      lumbar lordosis and promotes LC-EF, the WO-BPS posture may be a better seating
      option for people sitting for a prolonged time.

PMID- 16571391
TI  - Internal consistency, stability, and validity of the spinal cord injury version
      of the multidimensional pain inventory.
AB  - OBJECTIVE: To evaluate the internal consistency, stability, and construct
      validity of a spinal cord injury (SCI) version of the Multidimensional Pain
      Inventory (MPI-SCI). DESIGN: Interview. SETTING: Veterans Affairs medical center
      and university-based institute. PARTICIPANTS: Community sample of persons with
      SCI and chronic pain (N=161). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE: The MPI-SCI. RESULTS: The internal consistency of the MPI-SCI subscales
      ranged from fair (.60) for affective distress to substantial (.94) for pain
      interference with activities. The subscales of the MPI-SCI (ie, life interference
      [r=.81], affective distress [r=.71], solicitous responses [r=.86], distracting
      responses [r=.85], general activity [r=.69], pain interference with activities
      [r=.78], pain severity [r=.69], negative responses [r=.69]) showed adequate
      stability. In contrast, the stability of the support (r=.59) and the life control
      subscales (r=.31) was unacceptably low. All MPI-SCI subscales with the exception
      of the perceived responses by significant others subscales showed good
      convergent, discriminant, and concurrent validity. CONCLUSIONS: The MPI-SCI
      appears to be a reasonable measure for evaluating chronic pain impact after SCI.
      In clinical trials, however, supplementary instruments should be included to
      assess changes in affect, social support, and perceptions of life control.

PMID- 16571392
TI  - Role of creatinine clearance as a screening test in persons with spinal cord
      injury.
AB  - OBJECTIVES: To determine (1) the variability of annual creatinine clearance
      (C(Cr)) testing for subjects with chronic spinal cord injury (SCI) and (2)
      whether decisions to change neurogenic bladder management are made based on C(Cr)
      measurements. DESIGN: Retrospective chart review. SETTING: Inpatient Veterans
      Affairs SCI unit. PARTICIPANTS: The medical records of 70 men were consecutively
      selected for review from among 664 veterans enrolled in the SCI clinic. All
      patient charts had to have at least 5 C(Cr) tests performed within 10 years
      preceding the review. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Development of renal insufficiency and change in medical or bladder management of
      the patient, based on the results of the C(Cr) test. RESULTS: For individual
      patients, the results of 24-hour C(Cr) were highly variable from 1 evaluation to
      the next; the within-subject standard deviation (SD) for C(Cr) was 25.9mL/min.
      The within-subject SD for serum creatinine was 0.12mg/dL. For all comparisons of
      repeatability, variability, and reliability, serum creatinine was superior to
      C(Cr). No medical management decisions were made based on the result of the 24
      hour creatinine clearance. Renal ultrasound results and postvoid bladder
      residuals were the major factors in changing medical management with regard to
      renal function preservation. CONCLUSIONS: The C(Cr) test has little value as a
      screening measure for renal disease in SCI patients because of its variability in
      serial testing.

PMID- 16571394
TI  - Neuromuscular electric stimulation effect on lower-extremity motor recovery and
      gait kinematics of patients with stroke: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effects of neuromuscular electric stimulation (NMES)
      of the tibialis anterior muscle on motor recovery and gait kinematics of patients
      with stroke. DESIGN: Randomized, controlled, assessor-blinded trial. SETTING:
      Rehabilitation ward and gait laboratory of a university hospital. PARTICIPANTS: A
      total of 25 consecutive inpatients with stroke (mean age, 55y), all within 6
      months poststroke and without volitional ankle dorsiflexion. INTERVENTION: Both
      the NMES group (n=12) and the control group (n=13) participated in a conventional
      stroke rehabilitation program, 5 days a week for 4 weeks. The NMES group also
      received 10 minutes of NMES to the tibialis anterior muscle of the paretic limb.
      MAIN OUTCOME MEASURES: Brunnstrom stages of motor recovery and kinematic
      characteristics of gait. RESULTS: Brunnstrom stages improved significantly in
      both groups (P<.05). In total, 58% of the NMES group and 61% of the control group
      gained voluntary ankle dorsiflexion. Between-group difference of percentage
      change was not significant (P>.05). Gait kinematics was improved in both groups,
      but the difference between groups was not significant. CONCLUSIONS: NMES of the
      tibialis anterior muscle combined with a conventional stroke rehabilitation
      program was not superior to a conventional stroke rehabilitation program alone,
      in terms of lower-extremity motor recovery and gait kinematics.

PMID- 16571393
TI  - Does therapeutic facilitation add to locomotor outcome of body weight--supported
      treadmill training in nonambulatory patients with stroke? A randomized controlled
      trial.
AB  - OBJECTIVE: To assess benefit of the facilitation technique (FT) coupled with body
      weight-supported treadmill training (BWSTT) in nonambulatory patients with
      stroke. DESIGN: Randomized controlled trial. SETTING: Inpatient rehabilitation
      hospital. PARTICIPANTS: Forty-nine patients with nonambulatory patients with
      stroke were randomly allocated to BWSTT coupled with the FT or mechanical
      assistance (control). INTERVENTIONS: Swinging and stance of the paretic leg were
      assisted using the FT or mechanically (control) during BWSTT. MAIN OUTCOME
      MEASURES: The FIM instrument, Fugl-Meyer Assessment, gait speed, and cadence.
      RESULTS: Demographic and clinical features of the FT (n=22) and control (n=25)
      groups on admission were comparable after excluding 2 dropouts. There were no
      differences in the gains of the main outcome measures between the FT and control
      groups. Patients with severe impairment in the FT group had greater gains in arm
      function than those in the control group. CONCLUSIONS: The FT did not add
      significantly to locomotor outcome of BWSTT in nonambulatory patients with stroke
      but it did require more therapists' assistance.

PMID- 16571396
TI  - Standing balance after vestibular stimulation in Tai Chi-practicing and
      nonpracticing healthy older adults.
AB  - OBJECTIVE: To compare the effects of vestibular stimulation on standing balance
      control between Tai Chi practitioners and older subjects. DESIGN: Cross-sectional
      study. SETTING: University-based rehabilitation center. PARTICIPANTS: Tai Chi
      practitioners (n=24; age +/- standard deviation, 69.3+/-5.0y) and control
      subjects (n=24; age, 71.6+/-6.1y) were recruited. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Subjects stood on a force platform with eyes closed before
      and after stimulation of their horizontal semicircular canals, applied by means
      of whole head-and-body rotation at 80 degrees /s for 60 seconds, with subjects
      seated in a rotational chair. Body sway during stance was measured as total sway
      path, peak amplitudes, and mean velocities of sway in both anteroposterior (AP)
      and mediolateral (ML) directions. RESULTS: After head-and-body rotation,
      significant within-group increases were found in all measures in both AP and ML
      directions during stance with eyes closed in older control subjects but not in
      Tai Chi practitioners along the AP direction. In fact, significantly smaller
      increases in total sway path, peak amplitude, and mean velocity of body sway in
      the AP direction were found in the Tai Chi practitioners when compared with those
      of control subjects. CONCLUSIONS: Our results show that long-term Tai Chi
      practitioners had better AP standing balance control after vestibular stimulation
      than older control subjects.

PMID- 16571395
TI  - Gait characteristics in nondisabled community-residing nonagenarians.
AB  - OBJECTIVE: To determine gait performance in community-residing nonagenarians.
      DESIGN: Nested case-control study. SETTING: Community. PARTICIPANTS: Thirty-one
      nondisabled nonagenarians (17 women) and 170 young-old controls (age range, 70
      85y) participating in a longitudinal study. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Systematic clinical and quantitative gait assessments. We also
      examined the association of gait velocity with death over a 1-year period.
      RESULTS: Nonagenarian men had better performance on all quantitative gait
      parameters examined compared with women. Male sex (beta=.58; 95% confidence
      interval [CI], 9.95-38.89) and depressive symptoms (beta=-.34; 95% CI, -6.73 to 
      0.04) were independently associated with gait velocity in multivariate linear
      regression models. The 6 hypertensive nonagenarians on angiotensin-converting
      enzyme (ACE) inhibitors had faster gait velocity (median, 103.1cm/s) compared
      with the 8 hypertensive nonagenarians not on ACE inhibitors (median, 77.5cm/s;
      P=.029). Nonagenarians had worse quantitative gait parameters compared with the
      young-old controls, although the differences were less marked when subjects with
      clinically normal gaits in both groups were compared. Gait velocity did not
      predict survival over 1-year follow-up. CONCLUSIONS: Gait characteristics in
      nondisabled community-residing nonagenarians are associated with male sex,
      depressive symptoms, and medications. The quantitative gait measures in this
      sample of nondisabled nonagenarians provide a yardstick to compare younger-age
      groups.

PMID- 16571397
TI  - The association of balance capacity and falls self-efficacy with history of
      falling in community-dwelling people with chronic stroke.
AB  - OBJECTIVES: To describe the frequency of falls; to relate capacity-based and self
      efficacy measures to fall history; and to determine to what extent capacity-based
      and self-efficacy measures are explained by subject characteristics and stroke
      impairments. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS:
      Convenience sample of 50 people with chronic stroke. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Fall history, Falls Efficacy Scale-Swedish
      Version, fear of falling, and the mood subscore of the Stroke Impact Scale.
      Balance, strength, and functional mobility were measured using the Berg Balance
      Scale, timed sit to stand, and Timed Up & Go, respectively. RESULTS: Falls were
      reported by 40% (n=20) of subjects; 22% (n=11) reported multiple falls. Subjects
      with fall history had more fear of falling (relative risk [RR], 2.4; 95%
      confidence interval [CI], 1.1-4.9), had less falls-related self-efficacy (P=.04),
      and more depressive symptoms (P=.02) than nonfallers. Subjects with multiple fall
      history had poorer balance (P=.02), more fear of falling (RR=5.6; 95% CI, 1.3
      23), and used a greater number of medications (P=.04) than non- and 1-time
      fallers. Strength partially explained balance, mobility, and falls-related self
      efficacy. CONCLUSIONS: Balance and falls-related self-efficacy are associated
      with fall history and should be addressed in people with chronic stroke.

PMID- 16571398
TI  - The relation between ankle impairments and gait velocity and symmetry in people
      with stroke.
AB  - OBJECTIVE: To identify the most important factor among the ankle impairments on
      gait velocity and symmetry in stroke patients. DESIGN: Cross-sectional,
      descriptive analysis of convenience sample. SETTING: Patients from outpatient
      rehabilitation and neurovascular neurology departments in medical centers and
      municipal hospitals in Taiwan. PARTICIPANTS: Sixty-eight subjects with
      hemiparesis poststroke with the ability to walk independently. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Maximal isometric strength of plantarflexors
      and dorsiflexors were examined by a handheld dynamometer. Spasticity index, slope
      magnitudes between electromyographic activities, and muscle lengthening velocity
      of gastrocnemius during lengthening period of stance phases were measured to
      represent the dynamic spasticity. Passive stiffness of pantarflexors was
      indicated by degrees of dorsiflexion range that were less than normative values.
      Position error was measured by the degree of proprioceptive deficits of ankle
      joint by evaluating the joint position sense. Gait velocity, symmetry, and other
      gait parameters were measured by the GAITRite system. RESULTS: Regression
      analyses revealed that the dorsiflexors strength was the most important factor
      for gait velocity and temporal symmetry (R(2)=.30 for gait velocity, P<.001;
      R(2)=.36 for temporal asymmetry, P<.001). Dynamic spasticity was the most
      important determinant for gait spatial symmetry (R(2)=.53, P<.001). CONCLUSIONS:
      Gait velocity and temporal asymmetry are mainly affected by the dorsiflexors
      strength, whereas dynamic spasticity of plantarflexors influenced the degree of
      spatial gait asymmetry in our patients who were able to walk outdoors. Treatment
      aiming to improve different aspects of gait performance should emphasize on
      different ankle impairments.

PMID- 16571399
TI  - Detection of gait instability using the center of mass and center of pressure
      inclination angles.
AB  - OBJECTIVE: To define a parameter that quantifies balance control during gait and
      better identifies elderly people who are at a higher risk of falling. DESIGN:
      Controlled study. SETTING: University research laboratory. PARTICIPANTS: Twelve
      elderly patients (mean age, 76.9+/-6y) with complaints of imbalance during
      walking, or with a history of falls, and 12 matched healthy elderly adults.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Temporal-distance gait
      parameters (gait velocity, stride length, step width); and sagittal and frontal
      center of mass (COM) and center of pressure (COP) inclination angles. RESULTS:
      Elderly patients demonstrated a significantly greater medial, but a significantly
      smaller anterior, inclination angle than their matched controls during both
      unobstructed and obstructed gait. The medial COM-COP inclination angle was not
      affected by the gait velocity in the healthy elderly. When the 2 groups were
      compared at a similar gait velocity ( approximately 1m/s), the elderly patients
      still had a significantly greater medial COM-COP inclination angle than did the
      controls. CONCLUSIONS: Instantaneous COM-COP inclination angles during walking
      provide information about the ability to control COM position in relation to the
      corresponding COP. The medial COM-COP inclination angle may be a sensitive
      measure of gait stability in the elderly.

PMID- 16571400
TI  - Reliability of the assessment of lumbar range of motion and maximal isometric
      strength.
AB  - OBJECTIVE: To examine the interobserver reliability and intrasubject variability
      of the assessment of lumbar range of motion (ROM) and maximal isometric strength
      in asymptomatic subjects by using commercially available equipment. DESIGN: A
      cross-sectional repeated-measures design. SETTING: Ambulatory care in a
      university hospital. PARTICIPANTS: Convenience sample of 61 asymptomatic healthy
      subjects aged 20 to 55 years. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Six movements of the lumbar spine were assessed with commercially
      available equipment. Both the ROM and the maximal isometric strength for flexion,
      extension, lateroflexion, and rotation of the lumbar spine were assessed by 2
      investigators who were blinded to the outcome of the assessment performed by
      their colleague. RESULTS: The intraclass correlation coefficient (ICC) was above
      .95 for all the strength measurements. For the assessment of the ROM of the
      lumbar spine, the ICC varied between .77 and .94. There was a significant
      intrasubject variability for 8 of 12 measurements. CONCLUSIONS: The interobserver
      reliability is excellent for the measurement of the maximal isometric strength
      and good for the assessment of the ROM of the lumbar spine. There is a
      significant intrasubject variability, which requires the use of the mean or the
      best value of different trials.

PMID- 16571401
TI  - Retroperitoneal false aneurysm presenting as anterior thigh pain and weakness: a
      case report.
AB  - This case highlights the importance of considering retroperitoneal pathology in
      the differential diagnosis of anterior thigh pain and weakness. We describe a
      woman in her mid seventies with a history of a left total hip arthroplasty and
      lumbar decompression who presented with left anterior thigh pain and left lower
      extremity weakness. A computed tomography scan of the retroperitoneum revealed a
      mass along the left iliopsoas muscle. An arteriogram revealed a large false
      aneurysm that communicated with the left common femoral artery. Surgery to resect
      the aneurysm revealed exposed parts of the hip replacement that may have
      contributed to the formation of the aneurysm. We concluded that imaging of the
      retroperitoneum should be considered in any patient presenting with anterior
      thigh pain and weakness.

PMID- 16571402
TI  - Long-term prevention of pressure ulcers in high-risk patients: a single case
      study of the use of gluteal neuromuscular electric stimulation.
AB  - OBJECTIVE: To evaluate the efficacy of gluteal neuromuscular electric stimulation
      (NMES) using implanted percutaneous electrodes to improve regional tissue health
      and decrease the risk of pressure ulcer development. DESIGN: Case study of long
      term use of gluteal NMES. SETTING: Community. PARTICIPANT: A patient with a C4
      level American Spinal Injury Association grade A spinal cord injury, 22 years
      postinjury at study enrollment, and a clinical history of regular grade II and
      occasional IV ischial pressure ulcers. INTERVENTION: Gluteal NMES using an
      electric stimulation system comprising a combination of implanted percutaneous
      electrodes and an external stimulator (controller). MAIN OUTCOME MEASURES:
      Objective measurements of tissue health comprising evaluation of gluteal muscle
      thickness, interface pressures, and regional blood flow. Subjective self-reported
      sitting tolerance. RESULTS: Increased gluteal muscle thickness and blood flow
      together with reduced regional interface pressures occurred. Weight-shifting
      because of alternating left and right gluteal NMES became more effective over
      time as the muscles strengthened. Sitting tolerance more than doubled.
      CONCLUSIONS: A gluteal NMES system has been developed that provides both improved
      regional tissue health and dynamic weight shifting while seated in the
      wheelchair. In the current case, regular daily use had a positive impact on
      multiple indirect indicators of tissue health. Continued use was indicated as the
      positive effects were lost when stimulation was discontinued.

PMID- 16571403
TI  - Medicine that overlooks the evidence.

PMID- 16571405
TI  - Acupuncture for upper-extremity rehabilitation in chronic stroke.

PMID- 16571407
TI  - The post-stroke rehabilitation outcomes project revisited.

PMID- 16571410
TI  - Impact of HLA-C and Bw epitopes disparity on liver transplantation outcome.
AB  - The occurrence of graft rejection episodes after orthotopic liver transplantation
      (OLT) despite the use of immunosuppressive drugs designed to suppress T
      lymphocyte functions, indicates the involvement of other types of cells in this
      process. The activity of natural killer cells and their killer immunoglobulin
      like receptors (KIR) is regulated by human leukocyte antigen (HLA) class I
      determinants; C and Bw epitopes. Because recipient/donor pairs are usually HLA
      mismatched, recipient natural killer alloreactivity may be the mediating factor
      in rejection. In this retrospective study, we have analyzed rejection occurrence
      and outcome in 66 OLT recipients, 42 with and 24 without C or Bw epitope
      disparity in the rejection direction. Recipients transplanted from donors with no
      C epitope disparity had significantly fewer rejection episodes in the first year
      after transplantation compared with recipients transplanted across C epitope
      disparity (p = 0.0002). Moreover, this effect was more pronounced when the
      outcome was analyzed in OLT recipients across negative crossmatching for the anti
      HLA class I and II antibodies. In contrast, Bw epitope disparity did not affect
      the outcome. In conclusion, C epitopes disparity between recipients and donors in
      the rejection direction appears to influence posttransplant liver outcome. This
      finding may be helpful in the choice of appropriate liver donor and planning
      immune suppression.

PMID- 16571411
TI  - HLA-C and KIR genes in hepatitis C virus infection.
AB  - Natural killer (NK) cells are key components of the innate antiviral immune
      response. NK cell function is regulated by the interaction of major
      histocompatibility complex class I molecules with NK inhibitory receptors. The
      aim of this study was to investigate the role of the HLA-C/KIR pair in hepatitis
      C virus clearance in our population. A total of 196 hepatitis C virus-infected
      patients (65 resolved and 131 with persistent infection) were included in the
      study. Genotyping of HLA-C was carried out using polymerase chain reaction
      followed by a reverse sequence-specific oligonucleotide probe detection system.
      NK receptor-specific polymerase chain reaction typing of KIR2DL1, KIR2DL2, and
      KIR2DL3 was performed on the same patient group. Frequencies of the KIR2DL2 gene
      and the KIR2DL2/KIR2DL2 genotype were lower among patients with persistent
      infection (32.3% vs 45.4% among resolved, P = 0.01, OR = 0.57, 95% CI = 0.36
      0.91; and 16.2% vs 32.3% among resolved, P = 0.02, OR = 0.41, 95% CI = 0.19
      0.87). Nevertheless, the frequency of the KIR2DL3 gene was higher among patients
      with persistent infection (66.9% vs 54.6% among resolved P = 0.02, OR = 1.68, 95%
      CI = 1.07-2.65). Trends toward lower frequencies of the HLA-C2C2 genotype and NK
      HLA interactions with strong and moderate affinity among the patients with
      persistent infection were also observed.

PMID- 16571412
TI  - A novel flow assay for the detection of cytokine secreting alloreactive T cells:
      application to immune monitoring.
AB  - The direct and indirect allorecognition pathways play an important role in graft
      rejection. We hypothesized that the presence of alloreactive memory T cells in
      the recipient's circulation increases the risk of rejection after
      transplantation. The objective of this study was to develop a noninvasive, immune
      monitoring tool that simultaneously measures donor-specific responses via both
      the direct and indirect recognition pathways. Our laboratory developed a whole
      blood flow cytometric cytokine secretion assay to identify interferon (IFN)-gamma
      secreting memory T cells in whole blood of renal transplant patients. The assay
      readily detected IFN-gamma producing CD3+ T cells in response to recall antigens
      tetanus toxoid, purified protein derivative, and alloantigens in whole blood from
      healthy controls. Analysis of sequential posttransplant blood samples from 19
      renal allograft recipients showed that alloimmune responses were higher in
      transplant recipients who had undergone acute rejection than in those without
      acute rejection episodes. In addition, patients showing increased creatinine
      levels 3 months after transplantation were more likely to exhibit alloimmune
      responses than recipients with stable graft function. The flow cytokine secretion
      assay provides a reliable and simple method for identification of patients at
      risk of acute rejection and early graft dysfunction.

PMID- 16571413
TI  - Immune activation at effector and gene expression levels after measles
      vaccination in healthy individuals: a pilot study.
AB  - Cellular immunity to measles vaccination is not fully understood at the effector
      response and gene expression levels. We enrolled 15 healthy individuals (15-25
      years old) previously vaccinated with two doses of measles-mumps-rubella-II
      vaccine to characterize their cellular immunity. We detected a spectrum of
      lymphoproliferative response (median stimulation indices of 3.4), low precursor
      frequencies of interferon-gamma (median 0.11%) and interleukin-4 (median 0.05%)
      by Elispot, and cosecretion of Th1 and Th2 cytokines after measles virus
      stimulation. Further, global gene expression was examined in five subjects from
      this cohort after vaccination with an additional dose of measles vaccine
      (Attenuax, Merck) to identify the genes involved in measles immunity. Linear
      mixed effect models were used to identify genes significantly up or downregulated
      in vivo between baseline and Days 7 and 14 after measles vaccination. Measles
      vaccination induced upregulation of a set of 80 genes, which play a role in
      measles immunity, signal transduction, apoptosis, cell proliferation, and
      metabolic pathways. Among the 34 genes that were downregulated, only interferon
      alpha is known to have a direct role in measles immunity. This study suggests
      that measles vaccination leads to activation of multiple cellular mechanisms that
      can override the immunosuppressant effects of the measles virus and induce
      immunity.

PMID- 16571414
TI  - Interleukin-12 increases proliferation and interferon-gamma production but not
      cytolytic activity of human antigen-specific effector memory cytotoxic T
      lymphocytes: power of the effect depends on the functional avidity of the T cell
      and the antigen concentration.
AB  - Cytotoxic T lymphocytes (CTLs) play an important role in the defense against
      viral infections and malignant diseases. Interleukin (IL)-12 plays a crucial role
      in induction of antigen-specific primary CTL responses and enhances
      proliferation, interferon-gamma (IFN-gamma) production, and cytolytic activity of
      mitogen-stimulated T cells. However, the effects of IL-12 on proliferation and
      effector functions of previously in vitro or in vivo primed antigen-specific CTLs
      are less clear. Our results show that IL-12 induces an increase in proliferation
      of and IFN-gamma production by influenza peptide-specific CTLs, but no increase
      in cytolytic activity on a per cell basis was observed in bulk cultures.
      Stimulation of a CTL clone confirmed these results; IL-12 supported an increase
      in IFN-gamma production, but did not increase cytolytic activity. The extent of
      the effect of IL-12 on IFN-gamma production differs per CTL clone and depends on
      the avidity of the clone and the peptide concentration on its target. Our data
      suggest that IL-12 is a good adjuvant for boosting CTL responses, in terms of
      proliferation and IFN-gamma production, the latter particularly for CTLs with low
      to intermediate avidity, such as tumor-associated self-antigen-specific CTLs.

PMID- 16571415
TI  - Induction of neutrophil extracellular DNA lattices by placental microparticles
      and IL-8 and their presence in preeclampsia.
AB  - Preeclampsia, a severe pregnancy-related disorder, involves an overt activation
      of the maternal innate immune system, proposed to result from the elevated
      release of inflammatory syncytiotrophoblast microparticles (STBM) and cytokines
      from underlying placental anomaly involving abnormal trophoblast differentiation.
      Activation of circulating neutrophils has recently been shown to lead to the
      generation of fibrous extracellular lattices containing DNA, termed NETs
      (neutrophil extracellular traps). Therefore, we examined whether placentally
      derived factors activated peripheral neutrophils to generate NETs, and whether
      NETs formation was increased in preeclamptic placenta. Activation of isolated
      circulatory neutrophils on treatment with placentally derived factors
      (interleukin-8 and STBM) was assessed by measuring CD11b expression using Flow
      cytometry. Furthermore, NETs generation by these activated neutrophils in vitro
      and in vivo in the placental tissue sections were examined using electron
      microscopy and fluorescence microscopy. We report that placentally-derived
      interleukin-8 and STBM efficiently activated neutrophils and triggered NETs
      formation. Large numbers of NETs were present directly in the intervillous space
      of preeclamptic placentae. NETs, therefore, appear to be an integral part of
      neutrophil activation, and their increased presence in preeclampsia suggests that
      NETs may play a role in the underlying pathology.

PMID- 16571416
TI  - Identification and characterization of HIV-1 epitopes presented by HLA-A*2603:
      comparison between HIV-1 epitopes presented by A*2601 and A*2603.
AB  - Human leukocyte antigen (HLA)-A*26 is one of the alleles associated with a slow
      progression to AIDS. Identification and characterization of HIV-1-specific
      epitopes presented by this allele are necessary for studies on the
      immunopathogenesis of AIDS and vaccine development in Asia, where three HLA-A*26
      subtypes are frequently found. In the present study, we sought to identify HLA
      A*2603-restricted HIV-1 epitopes by using reverse immunogenetics and to compare
      them with HLA-A*2601-restricted ones recently identified. We found that 31 of 110
      HIV-1 peptides bound to HLA-A*2603 and that only two peptides (Gag169-177 and
      Env63-72) induced specific CD8+T cells by stimulating peripheral blood
      mononuclear leukocytes from HIV-1-infected individuals carrying HLA-A*2603. The
      specific cytotoxic T lymphocyte clones killed HIV-1 recombinant vaccinia-infected
      cells, indicating that these two peptides were naturally occurring peptides
      presented by HLA-A*2603. Gag169-177-specific CD8+T cells were frequently detected
      in both HLA-A*2601+ and -A*2603+ individuals with chronic HIV-1 infection,
      whereas Env63-72-specific ones were frequently detected only in the HLA-A*2603+
      individuals. Gag169-177 peptide bound equally to both HLA-A*26 antigens, whereas
      Env63-72 peptide bound to A*2603 much more strongly than to A*2601. These
      findings suggest that the relative affinity of these peptides for the HLA-A*26
      subtypes determines whether these peptides are recognized as epitopes in HIV-1
      infected individuals carrying these alleles.

PMID- 16571417
TI  - Frequent HLA class I loss is an early event in cervical carcinogenesis.
AB  - Loss at chromosome 6p21.3, the human leukocyte antigen (HLA) region, is the main
      cause of HLA downregulation, occurring in the majority of invasive cervical
      carcinomas. To identify the stage of tumor development at which HLA class I
      aberrations occur, we selected 12 patients with cervical carcinoma and adjacent
      cervical intraepithelial neoplasia (CIN). We investigated HLA class I and beta2
      microglobulin expression by immunohistochemistry in tumor and adjacent CIN. Loss
      of heterozygosity (LOH) was studied using microsatellite markers covering the HLA
      region. Fluorescent in situ hybridization with HLA class I probes was performed
      to investigate the mechanism of HLA loss. Immunohistochemistry showed absent or
      weak HLA class I expression in 11/12 cases. In 10 of these 11 cases,
      downregulation occurred in both tumor and CIN. Only in one case did the
      concomitant CIN lesion show normal expression. In 9/12 cases, LOH was present for
      at least one marker in both tumor and CIN, 1 case showed only LOH in the CIN
      lesion, and 1 case showed retention of heterozygosity for all markers in both
      tumor and CIN. We conclude that HLA class I aberrations occur early and
      frequently in cervical carcinogenesis. This might allow premalignant CIN lesions
      to escape immune surveillance and progress to invasive cancer.

PMID- 16571418
TI  - Multiplex genotyping of human minor histocompatibility antigens.
AB  - Minor histocompatibility antigens (mHAg) induce major histocompatibility complex
      restricted, T cell-mediated immune responses that may contribute to increased
      risk of graft-versus-host disease and graft-versus-leukemia effects. Unlike human
      leukocyte antigen genes, mHAg are encoded by genetically and functionally
      unrelated genes located throughout the chromosome. The role of mHAg in stem cell
      transplantation and the population frequencies of mHAg alleles remain unknown due
      in part to the lack of suitable high throughput methods for genotyping these
      diverse genes. Here we describe the development and utility of a multiplexed
      Luminex assay for genotyping human mHAg, including HA-1, HA-2, HA-3, HA-8, HB-1,
      CD31(125), and CD31(563). The assay uses a multiplexed, allele-independent, gated
      amplification of mHAg genes followed by differential detection of allele-specific
      primer extension products using the MultiCode PLx system (EraGen Biosciences,
      Madison, WI). The alleles are interrogated using a multiplex allele-specific
      primer extension reaction using primers tagged with EraCodes. The products are
      hybridized to Luminex beads and the hybridization duplexes are detected using
      streptavidin-phycoerythrin. The assay resolved the mHAg genotypes of 259
      Caucasian donors and provided population estimates of mHAg gene and phenotypic
      frequencies. All mHAg alleles evaluated in this study exhibited Hardy-Weinberg
      equilibrium, although some mHAg phenotypes were present in large majority of
      individuals tested (HA-2, HB-1). This assay will provide a valuable tool for
      determining mHAg frequencies in other ethnic populations, as well as for
      establishing the clinical importance of mHAg disparities in stem cell
      transplantation.

PMID- 16571419
TI  - Nomenclature for factors of the HLA system, update July 2005.

PMID- 16571422
TI  - The importance of registering clinical trials.

PMID- 16571423
TI  - Evaluating individual surgeons based on total hospital costs: evidence for
      variation in both total costs and volatility of costs.
AB  - BACKGROUND: There is increasing interest in evaluating quality in health care,
      extending to the assessment of outcomes, including costs, for individual
      surgeons. STUDY DESIGN: Surgical patients entered in the private sector National
      Surgical Quality Improvement Program at the University of Michigan Medical Center
      between September 2003 and September 2004 were included. Patient level
      characteristics and outcomes measures were combined with internal hospital cost
      data. Analysis was performed at the individual surgeon level using hospital costs
      as the outcomes variable, controlling for patient case-mix variables and
      procedural complexity. We used an econometric statistical model combining
      ordinary least squares and quantile regression methods, which allowed us to
      examine the effect of individual surgeons on costs. RESULTS: Considerable
      variation in costs across surgeons is demonstrated, holding patient case mix and
      procedural complexity constant. This is shown for mean estimates (p<0.001) and
      estimates of 10th (p=0.001), 50th (p<0.001), and 90th (p=0.013) percentiles.
      Examining the 10th to 90th interquantile range also demonstrates substantial
      variation in the ranges of costs for surgeons (p=0.005), implying volatility in
      costs across providers, again holding patient case mix and procedural complexity
      constant. In dollar terms, 6 of 28 surgeons differ from a reference surgeon by
      39% or more. CONCLUSIONS: Individual surgeons appear to have statistically and
      clinically significant differences in their costs and volatility of costs when
      holding patient factors and procedural complexity constant. Implications for
      quality improvement and incentive programs are discussed.

PMID- 16571424
TI  - Open versus endovascular abdominal aortic aneurysm repair in VA hospitals.
AB  - BACKGROUND: Endovascular abdominal aortic aneurysm repair (EVAR), when compared
      with conventional open surgical repair, has been shown to reduce perioperative
      morbidity and mortality. We performed a retrospective cohort study with
      prospectively collected data from the Department of Veterans Affairs to examine
      outcomes after elective aneurysm repair. STUDY DESIGN: We studied 30-day
      mortality, 1-year survival, and postoperative complications in 1,904 patients who
      underwent elective abdominal aortic aneurysm repair (EVAR n=717 [37.7%]; open
      n=1,187 [62.3%]) at 123 Department of Veterans Affairs hospitals between May 1,
      2001 and September 30, 2003. We investigated the influence of patient, operative,
      and hospital variables on outcomes. RESULTS: Patients undergoing EVAR had
      significantly lower 30-day (3.1% versus 5.6%, p=0.01) and 1- year mortality rates
      (8.7% versus 12.1%, p=0.018) than patients having open repair. EVAR was
      associated with a decrease in 30-day postoperative mortality (adjusted odds
      ratio[OR]=0.59; 95% CI=0.36, 0.99; p=0.04). The risk of perioperative
      complications was much less after EVAR (15.5% versus 27.7%; p<0.001; unadjusted
      OR 0.48; 95% CI=0.38, 0.61; p<0.001). Patients operated on at low volume
      hospitals (25% of entire cohort) were more likely to have had open repair (31.3%
      compared with 15.9% EVAR; p<0.001) and a nearly two-fold increase in adjusted 30
      day mortality risk (OR=1.9; 95% CI=1.19, 2.98; p=0.006). CONCLUSIONS: In routine
      daily practice, veterans who undergo elective EVAR have substantially lower
      perioperative mortality and morbidity rates compared with patients having open
      repair. The benefits of a minimally invasive approach were readily apparent in
      this cohort, but we recommend using caution in choosing EVAR for all elective
      abdominal aortic aneurysm repairs until longer-term data on device durability are
      available.

PMID- 16571425
TI  - Modern 5-year survival of resectable esophageal adenocarcinoma: single
      institution experience with 263 patients.
AB  - BACKGROUND: Surgery, as the mainstay of treatment for localized esophageal
      cancer, is currently being challenged by the assumed high risk of esophagectomy
      and the poor longterm survival after resection. Epidemiologic and clinical
      changes over the past decade indicate that these assumptions should be
      reevaluated. The aim of this study was to assess the modern outcomes of
      esophagectomy for adenocarcinoma. STUDY DESIGN: We studied 263 consecutive
      patients (215 men, 48 women), who had esophagectomy for adenocarcinoma from 1992
      to 2002. Ninety-seven (37%) were stage I, 63 (24%) were stage II, 93 (35%) were
      stage III, and 10 (4%) were stage IV. Forty-five percent (119 of 263) had
      curative en bloc resection, 52% (138 of 263) had node involvement, and 18% (48)
      received neoadjuvant therapy. RESULTS: Seventeen percent (44 of 263) of the
      patients were identified in a Barrett's surveillance program. The frequency of
      T1N0 adenocarcinoma increased over the study period (p=0.024). The overall 5-year
      survival was 46.5%, and for the last 5 years of the study was 50.4%. The overall
      5-year survival for stage I was 81%; for stage II, 51%; for stage III, 14%; and
      for stage IV, 0%. Complications occurred in 61% and there were 12 perioperative
      deaths (4.5%). Cox proportional hazard analysis identified tumor stage and type
      of resection as independent predictors of survival. CONCLUSIONS: Nearly half of
      patients undergoing esophagectomy for adenocarcinoma survive >or=5 years.
      Improvements in survival are associated with increased detection of early stage
      disease, and a liberal use of en bloc resection. Nonsurgical treatments should be
      compared with these contemporary outcomes measures.

PMID- 16571429
TI  - Proficiency maintenance: impact of ongoing simulator training on laparoscopic
      skill retention.
AB  - BACKGROUND: Proficiency-based training in laparoscopic suturing and knot tying
      translates to the operating room, but little is known about the durability of
      acquired skill. The purpose of this study was to determine the effect of
      maintenance training on skill retention after demonstration of proficiency. STUDY
      DESIGN: Medical students (n=18) with no previous laparoscopic or simulator
      experience were enrolled in an IRB-approved randomized controlled trial. All
      subjects trained to proficiency (score of 512, based on time and errors) on a
      previously validated suturing model (Fundamentals of Laparoscopic Surgery
      videotrainer). Subjects were then randomized to a control group, which received
      no additional training, and an ongoing training group, which trained again to
      proficiency at 1 and 3 months (immediately after testing). Simulator testing was
      repeated at 2 weeks, 1 month, 3 months, and 6 months after initial training. No
      subject had interval operative experience. RESULTS: Both groups demonstrated
      excellent skill retention during followup; performance scores, reported as
      means+/-SD, were 488+/-57 versus 482+/-55 at 2 weeks (p=ns), 483+/-81 versus
      491+/-64 at 1 month (p=ns), 467+/-75 versus 470+/-67 at 3 months (p=ns), and
      462+/-62 versus 492+/-43 at 6 months (p=0.02) for the control versus ongoing
      training groups, respectively. At 6 months, the ongoing training group showed
      better skill retention (95% versus 90%; p=0.02) and a trend for achieving the
      proficiency level (33% versus 18%; p=0.2) more often than the control group.
      CONCLUSIONS: Although proficiency-based training results in excellent skill
      retention, ongoing training substantially enhances performance and minimizes
      skill loss. Curricula should incorporate training that fosters maintenance of
      proficiency.

PMID- 16571430
TI  - Preoperative esophageal cancer staging: magnetic resonance imaging of lymph node
      with ferumoxtran-10, an ultrasmall superparamagnetic iron oxide.
AB  - BACKGROUND: Accurate detection of metastasis to lymph nodes is an essential
      component of the approach to treatment. The purpose of this study was to evaluate
      the utility of magnetic resonance imaging with ferumoxtran-10 in diagnosing lymph
      node metastasis in esophageal cancer. STUDY DESIGN: Sixteen patients with
      esophageal cancer who were scheduled for surgical lymph node dissection were
      enrolled. All patients underwent MRI scanning before and 24 hours after
      intravenous administration of ferumoxtran-10, an ultrasmall, superparamagnetic
      iron oxide. The presence or absence of metastasis was identified in lymph nodes
      by their enhancement patterns. Nonmalignant nodes contained macrophages that
      phagocytosed ferumoxtran-10. Metastatic nodes exhibited a decrease in phagocytic
      activity, and consequently showed little or no uptake of ferumoxtran-10. So we
      subdivided the enhancement patterns into the following three patterns: (A) node
      having an overall low signal intensity, (B) node having an area of high signal
      intensity, and (C) node having an overall high signal intensity. We identified
      that patterns (B) and (C) were metastatic patterns. The imaging results were
      compared with histopathologic findings. RESULTS: Of the 408 resected lymph nodes,
      imaging results of 133 nodes could be compared with histopathologic findings.
      Twenty-four lymph nodes had histopathologic metastases. Using our enhancement
      criteria, sensitivity was 100%, specificity was 95.4%, and accuracy was 96.2% for
      diagnosis of metastatic nodes. CONCLUSIONS: Ferumoxtran-10 is useful for
      characterizing benign or malignant lymph nodes in esophageal cancer patients
      based on the defined enhancement criteria.

PMID- 16571431
TI  - Prophylactic gastrectomy for hereditary diffuse gastric cancer syndrome.
AB  - BACKGROUND: Germline mutations in the E-cadherin gene, CDH1, were recently
      identified in families with hereditary diffuse gastric cancer. The efficacy of
      endoscopic surveillance by current methods is largely ineffective because most
      tumors spread diffusely. There has been little evidence that prophylactic
      gastrectomy should be performed in patients with the genetic mutation, and few
      data are available on the outcomes of operations in patients with the CDH1
      mutation undergoing prophylactic gastrectomy. We report the outcomes of patients
      with the CDH1 mutation who have undergone prophylactic gastrectomy in the year
      2003 to 2004. STUDY DESIGN: After genetic counseling and informed consent, two
      patients underwent total gastrectomy with Roux-en-Y reconstruction. Demographic
      information, pedigree analysis, preoperative screening results, operative course,
      and postoperative data, including complications, were collected and reviewed for
      each patient. RESULTS: Pathologic examination of the stomach revealed no evidence
      of in situ or invasive carcinoma. There were no operative complications. Both
      patients reported diarrhea and moderate weight loss. There were no other
      postoperative complications. CONCLUSIONS: Prophylactic gastrectomy can be
      performed safely, without mortality or severe morbidity, in patients with CDH1
      mutations, and should be curative in this population of patients.

PMID- 16571432
TI  - Percutaneous tracheostomy: a safe procedure in the morbidly obese.
AB  - BACKGROUND: Percutaneous dilational tracheostomy (PDT) is becoming a widely
      accepted technique that has replaced open tracheostomy (OT) in many hospitals.
      One of the remaining relative contraindications is morbid obesity. There are no
      published case series of its use in this patient population. We reviewed our
      experience with PDT in the morbidly obese and compared it to OT in this patient
      population. Our hypothesis is that PDT and OT have a similar frequency of adverse
      events. STUDY DESIGN: We reviewed charts of all morbidly obese patients (body
      mass index [BMI]>or=35, calculated as kg/m2) undergoing either PDT or OT at our
      institution during a 58-month period. Variables examined included age, gender,
      BMI, diagnosis, bedside or operating room, and bronchoscopy-assisted. We recorded
      all procedural complications and all tracheostomy-related complications that
      occurred for 30 days postprocedure or death. Primary adverse end points were
      defined as procedures that started percutaneous and converted to open; any
      reoperation related to the initial tracheostomy; malpositioning of tracheostomy
      resulting in patient morbidity, loss of airway control, and bleeding requiring
      surgical intervention. Secondary adverse end points occurred when a tracheostomy
      tube was dislodged or malfunctioned, as in the case of a cuff leak, and any
      bleeding that occurred more than 24 hours after insertion. RESULTS: From January
      1, 2000, until September 30, 2004, our institution performed 1,062
      tracheostomies. One hundred forty-three patients had a BMI>or=35. Eighty-nine
      patients underwent PDT and 53 patients underwent OT. Sixty-seven of the PDTs were
      performed at the bedside and 22 were performed in the operating room. All OTs
      were performed in the operating room. Five (6.5%) primary end points were
      recorded for PDTs (4 conversions to open, 1 malpositioning). Three (6.5%) primary
      end points were reported for OTs (malpositioning resulting in hypoxia, bleeding
      requiring surgical intervention, aborted attempt at open). CONCLUSIONS: PDT is a
      safe procedure to perform on morbidly obese patients.

PMID- 16571433
TI  - Current incidence and outcomes of gastrointestinal mesenchymal tumors including
      gastrointestinal stromal tumors.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) have been recognized as the
      most common mesenchymal tumors of the gastrointestinal tract. The most effective
      treatment for unresectable tumors is imatinib mesylate, based on two phase II
      trials. Because no phase III clinical trial has been undertaken, we sought to
      determine both current population-based incidence and whether improved outcomes
      noted in both individual centers and clinical trials have also been observed in a
      large prospective cancer registry earlier and after the introduction of imatinib.
      STUDY DESIGN: The 13-center cumulative tumor registry (April 2005 release) from
      the Surveillance, Epidemiology, and End Results (SEER) database was queried from
      1992 to 2002 to determine incidence and associated outcomes for patients
      diagnosed with GIST. Confirmations of incidence trends using the incident Florida
      Cancer Data System (FCDS, 2005 release) were also determined. RESULTS: A 25-fold
      age-adjusted increase in incidence of GIST, from 0.028 per 100,000 in 1992 to
      0.688 per 100,000 in 2002, was observed. This increase is mostly because smooth
      muscle tumors have been reclassified as GISTs, but it also represents a 50%
      increase in population- and age-adjusted gastrointestinal mesenchymal tumor
      diagnosis since 1992. Despite rising GIST incidence rates, there has been a
      marked improvement in survival since 2000, coinciding with the introduction of
      the tyrosine kinase inhibitor imatinib into clinical practice. CONCLUSIONS: The
      diagnosis of GIST has dramatically increased since 1992. Survivals have greatly
      improved since 2000, when imatinib mesylate was FDA approved.

PMID- 16571434
TI  - Resistance to change in surgical residency: an ethnographic study of work hours
      reform.
AB  - BACKGROUND: Although the practical challenges to work hour restrictions have been
      the focus of much discussion, cultural resistance to such change has received
      less attention. Surgical residency has its own unique social structure, and we
      hypothesized that challenges to this would provide impediments to successful
      implementation of duty hours reform. STUDY DESIGN: We used ethnographic research
      methods to study the efforts at work hour restriction over a 15-month period
      before the introduction of the Accreditation Council for Graduate Medical
      Education regulations. These methods, validated for studying institutional
      change, build on intense periods of observation. Records of observations are then
      analyzed and coded to uncover cultural and political challenges. The frequency of
      successful hand-offs in sign-out situations between day and night float residents
      was measured as an objective index of success. RESULTS: Practical issues were
      addressed initially by scheduling adjustments including creating a night float
      system. The hand-offs that this system required, however, were successful only
      14% of the time. Subsequent steps to address the challenge to resident identity
      by top-down support of a new definition of professionalism increased the number
      of successful hand-offs to 39%. Finally, a reduction in a noted hierarchy
      violation led to successful hand-offs 79% of the time. CONCLUSIONS: These results
      demonstrate that practical solutions alone may not be a sufficient basis for
      change in surgical residency. While we face other challenges to the traditional
      surgical culture, attention to social and political issues may enhance the
      success of our efforts.

PMID- 16571435
TI  - Three-step ileal pouch-anal anastomosis under total laparoscopic approach for
      acute or severe colitis complicating inflammatory bowel disease.
AB  - BACKGROUND: A two- or three-step procedure is mandatory for restorative
      proctocolectomy in patients presenting with severe or acute colitis complicating
      inflammatory bowel disease (IBD). The aim of this study was to analyze the
      feasibility of a total laparoscopic approach for consecutive subtotal colectomy
      (STC) and secondary ileal pouch-anal anastomosis (IPAA). STUDY DESIGN: All
      patients underwent a three-step procedure that included first, a laparoscopic STC
      with ileostomy and sigmoidostomy; second, a laparoscopic proctectomy and IPAA,
      and third, closure of the temporary ileostomy. RESULTS: Eighteen consecutive
      patients (7 women and 11 men), with a mean age of 39+/-14 years (range 15 to 59
      years) were included. Mean lengths of the procedures were 252+/-59 minutes for
      STC, and 286+/-46 minutes for IPAA, respectively. Two patients (11%) after
      laparoscopic IPAA required conversion into laparotomy. No patient died
      postoperatively. Four patients had reoperations after laparoscopic IPAA for
      intraperitoneal hemorrhage by laparotomy (n=2) and by a transanal approach for
      anastomotic leakage (n=2). The overall morbidity rate was 33% (12 of 36
      procedures). Mean hospital stay was 8+/-2 days after STC, and 10+/-2 days after
      IPAA. After a mean follow up of 13 months, all patients underwent intestinal
      continuity restoration. CONCLUSIONS: Our study suggests that a total laparoscopic
      approach is feasible and safe in inflammatory bowel disease patients with acute
      or severe colitis, not only for STC but also for IPAA after STC, with no
      mortality and an acceptable morbidity rate.

PMID- 16571436
TI  - Does body armor protect from firearm injuries?
AB  - BACKGROUND: Bullet-proof vests and helmets protect from harm in combat and
      military engagements. The use of armor against shrapnel has been studied, yet
      little has been documented as to how they protect from high velocity gunshots.
      This study aims to describe the medical consequences of high velocity firearm
      injuries and to differentiate between patients injured while using protective
      wear and those injured unprotected. STUDY DESIGN: National trauma registry data
      on injury characteristics, treatment and outcomes between October 1, 2000 and
      December 31, 2003 were retrieved and analyzed. RESULTS: There were 669 terror
      related firearm injuries recorded: 236 (37.8%) in soldiers (protected) and 433
      (62.2%) in civilians (unprotected). Injury severity was notably higher in
      civilian patients (31% versus 16% with Injury Severity Score>or=16). Civilians
      had more ICU care (26% versus 20%, p=0.06), and double the inpatient mortality
      (8.6% [n=37] versus 3.4% [n=8] patients). Protected body regions such as abdomen,
      chest, and brain, were injured less frequently. Once a traumatic brain injury was
      sustained, no statistical differences were found in severity distribution, ICU
      stay, or inpatient death between protected and unprotected patients. But injury
      severity in patients with chest injuries was much higher in those who were
      unprotected (Injury Severity Score>or=25, 41% versus 23%, respectively, p=0.08).
      This increased severity could be attributed partly to more multiple injuries
      involving the chest. Abdominal injuries showed a similar pattern. CONCLUSIONS:
      Body armor has a protective effect on victims of high velocity gunshot wounds;
      lower rates of head, brain, chest, and abdominal injuries are seen. In addition,
      armor reduces the severity of injuries to the chest and the abdomen.

PMID- 16571437
TI  - Predictors for resident success in otolaryngology.
AB  - BACKGROUND: This study aimed to determine predictors for otolaryngology resident
      success using data available at the time candidates are interviewed (eg, medical
      school attended, letters of recommendation, test scores) and data that emerge
      during residency. STUDY DESIGN: We performed a retrospective cohort study of 36
      residents who entered our program between 1983 and 1993. RESULTS: Seventy percent
      of Alpha Omega Alpha (AOA) members and 13% of nonmembers were in the highest
      tertile based on faculty ranking (p<0.01), and candidates with an exceptional
      trait were more likely than those without an exceptional trait to rank in the
      highest tertile (57% versus 10%, p<0.01). AOA membership was also related to
      current academic appointment (p=0.02). Significant correlations included United
      States Medical Licensing Examination (USMLE) I score, year 2 in-training score
      (0.48, p=0.03), and years 3 and 4 in-training score and faculty ranking (minus
      0.39, minus 0.50, respectively, p<or=0.01). Having more than one peer-reviewed
      publication was associated with higher USMLE I scores and being favored for
      selection by >50% of the interviewers (p<0.05 for both). CONCLUSIONS: In our
      program designed to train academic otolaryngologists, postresident success was
      strongly predicted by having an exceptional trait and AOA membership. Success
      during residency was predicted by interviewer's impression of the candidate and a
      USMLE I score>570. Knowledge of these factors at the time of the resident
      interview could increase the likelihood of selecting the most appropriate
      candidates for academic otolaryngology. Resident success is a complex outcome,
      and other unmeasured and unexamined characteristics can provide additional
      insight into choosing successful residents.

PMID- 16571438
TI  - Making the case for a paradigm shift in trauma surgery.

PMID- 16571439
TI  - The secondary abdominal compartment syndrome: iatrogenic or unavoidable?

PMID- 16571440
TI  - Update on the surgical approach to mucocele of the appendix.

PMID- 16571441
TI  - Recent clinical and investigational applications of fibrin sealant in selected
      surgical specialties.

PMID- 16571442
TI  - Acute care surgery: Eraritjaritjaka.

PMID- 16571444
TI  - Free perforation of the gallbladder with pneumoperitoneum.

PMID- 16571445
TI  - Blunt ureteropelvic junction disruption.

PMID- 16571446
TI  - Laparoscopic ventral hernia repair: 5-mm port technique and alternative mesh
      insertion method.

PMID- 16571447
TI  - Surgical management of recurrent liver tumors involving hepatic venous outflow.

PMID- 16571448
TI  - Esophageal stoma for decompression of malignant obstruction.

PMID- 16571449
TI  - A meta-analytic review of verbal fluency deficits in schizophrenia relative to
      other neurocognitive deficits.
AB  - INTRODUCTION: A prominent view in the neuropsychological literature is that
      schizophrenia is particularly associated with executive dysfunction, yet in a
      meta-analytic review it was concluded that, relative to their general level of
      intellectual functioning, schizophrenics are not disproportionately impaired on a
      measure of this construct, the Wisconsin Card Sorting Test (WCST). However,
      verbal fluency tests may be more valid measures of executive functioning as they
      are more sensitive to the presence of focal frontal lobe injuries. METHOD: A meta
      analysis was conducted on 84 studies comparing the performance of schizophrenics
      and healthy controls on tests of phonemic and semantic fluency, as well as other
      cognitive measures presumed to impose only minimal demands on executive
      functioning. RESULTS: Neither phonemic or semantic fluency deficits qualified as
      differential deficits relative to general intelligence or psychomotor speed.
      Patients with schizophrenia were significantly more impaired on semantic relative
      to phonemic fluency. CONCLUSIONS: As for the WCST, deficits on tests of verbal
      fluency reflect a more generalised intellectual impairment and not particular
      difficulties with executive control processes. The larger deficit for semantic
      relative to phonemic fluency suggests that, in addition to general retrieval
      difficulties, schizophrenia is associated with compromises to the semantic store.

PMID- 16571450
TI  - Automatic processing of facial emotion in schizophrenia with and without
      affective negative symptoms.
AB  - INTRODUCTION: It is assumed that people spontaneously evaluate any incoming
      stimulus as pleasant or unpleasant. The evaluative response appears to structure
      perception and to have direct links to emotional states. METHODS: To investigate
      the automatic processing of face valence a sequential priming task based on
      emotional face stimuli was administered to schizophrenia patients with a flat
      affect expression, schizophrenia patients suffering from anhedonia, schizophrenia
      patients not suffering from anhedonia or flat affect, and healthy controls. The
      Scale for the Assessment of Negative Symptoms (Andreasen, 1989) was applied to
      evaluate affective symptoms and categorize patients into groups. RESULTS:
      Schizophrenia patients without affective negative symptoms exhibited reversed
      priming effects similar to that of healthy subjects. In contrast, flat affect
      patients and anhedonic patients showed only a prime effect due to negative facial
      valence. In the flat affect patient group, negative prime faces facilitated the
      evaluation of target faces, whereas in the anhedonic patient group negative prime
      faces tended to inhibit the evaluation of subsequent target faces. CONCLUSIONS:
      The present findings support the idea that chronic schizophrenia patients extract
      automatically the valence of emotional facial expression but they also suggest
      processing differences between schizophrenia patients as a function of affective
      symptoms.

PMID- 16571451
TI  - What happens to semantic memory when formal thought disorder remits? Revisiting a
      case study.
AB  - INTRODUCTION: Laws, Kondel, and McKenna (1999) previously reported a case study
      analysis of a schizophrenic patient (TC) with severe formal thought disorder
      (FTD). Examining consistency across item and modality of input, Laws et al.
      documented an impairment of access to semantic knowledge in TC. METHOD: Following
      substantial improvement in his FTD, we readministered the same extensive battery
      of neuropsychological tests tapping semantic memory functioning. RESULTS: Whilst
      TC's naming remained relatively good, it also became more consistent across both
      time and modality. Tasks tapping language comprehension and understanding of
      semantic association revealed some significant improvements. Nevertheless, TC
      showed a residual propensity to verify false information. CONCLUSION: Improvement
      in FTD in schizophrenia was accompanied by a better and more stable semantic
      memory performance in TC. The findings are consistent with, and expand upon the
      original suggestion that thought disorder reflects disorganised access to
      semantic memory.

PMID- 16571453
TI  - Testing the extreme male brain (EMB) theory of autism: let the data speak for
      themselves.

PMID- 16571454
TI  - Schizophrenia, theory of mind, and persecutory delusions.
AB  - INTRODUCTION: There is already a substantial body of evidence supporting Frith's
      (1992) theory that theory of mind (ToM) is impaired in people with schizophrenia.
      However, a specific relationship between impaired ToM and paranoid delusions,
      while intuitively reasonable, has only been demonstrated in two studies to date.
      METHODS: A total of 25 participants with schizophrenia were classified as
      paranoid or nonparanoid and compared with 38 healthy controls on a variety of ToM
      tasks. These tasks included verbal and nonverbal, and first and second order ToM
      tasks. RESULTS: Participants with schizophrenia performed significantly more
      poorly than healthy controls on both the first and second order verbal ToM tasks
      but not on the nonverbal ToM tasks. However, the ToM deficit was only observed
      for those participants with schizophrenia who had persecutory delusions. There
      was also a strong relationship observed between the severity of persecutory
      delusions and length of illness. CONCLUSIONS: This study represents only the
      third demonstration of a specific link between paranoid delusions and ToM
      impairment. Reasons why previous findings on this issue have been so inconsistent
      are considered. Further research is needed to explore the relationships among
      paranoia, ToM, and length of illness.

PMID- 16571455
TI  - Source monitoring for actions in hallucination proneness.
AB  - INTRODUCTION: In the present study we explored the role of cognitive factors in
      hallucinatory proneness by utilising an incidental source monitoring task
      consisting of actions. METHOD: A total of 65 normal subjects were administered a
      source monitoring task and were asked either to: (1) perform the action; (2)
      watch the experimenter perform the action; (3) imagine him/herself performing the
      action; (4) imagine the experimenter performing the action; (5) or listen to the
      experimenter say the action verbally. Following a delay, actions were presented
      consisting of those already presented in one of the 5 conditions (old), and those
      never before presented (new). For each action, subjects were required to identify
      if the action was old or new. If the action was identified as old, subjects were
      required to identify the source of the word (i.e., one of the 5 conditions).
      Subjects also completed a questionnaire assessing metacognitive beliefs. Subjects
      were grouped according to their scores on a revised and elaborated version of the
      Launay-Slade Hallucinations Scale (LSHS). Those with scores within the top 25%
      were included in the hallucination-prone group (HP) (n = 16), whereas scores
      within the lower 25% were included in the nonhallucination-prone group (NHP) (n =
      16). RESULTS: Within the internal conditions, hallucination-prone subjects
      confused two internal sources (a specific internal-internal source discrimination
      error). That is, for imagined actions where the subjects performed the action, HP
      subjects erroneously attributed these towards an imagined action performed by the
      experimenter. Results also revealed that hallucination-proneness was associated
      with metacognitive beliefs. Finally, there was a significant relation between
      certain metacognitive beliefs and the internal-internal source discrimination
      error on the source monitoring task. CONCLUSIONS: Findings from the present study
      suggest that an important cognitive deficit in the genesis of hallucinations may
      be a perturbation in the control of internally generated cognitive events.

PMID- 16571456
TI  - Auditory hallucinations: failure to inhibit irrelevant memories.
AB  - INTRODUCTION: The frequency of auditory hallucinations (AH) is associated with
      efficiency in inhibiting irrelevant memories, suggesting that the presence of AH
      may be related to the intrusion of strongly activated representations in memory.
      Therefore, we hypothesised that the inability to suppress irrelevant memories
      would be found only in patients currently experiencing AH. METHOD: Performance on
      a repeated, continuous recognition task was examined in 23 schizophrenia patients
      with AH present, 20 schizophrenia patients with AH absent, and 24 healthy
      controls. RESULTS: Patients with current AH made significantly more inappropriate
      responses (false alarms) to distractors seen on previous runs of the task than
      nonhallucinating patients. The ability to detect targets (hits) was significantly
      better in healthy controls than schizophrenia patients, however, there was no
      significant difference between the two patient subgroups. CONCLUSIONS: The
      findings confirm that the presence of AH involves a failure to suppress memories
      that are not relevant to ongoing reality. We propose that a combination of
      deficits in inhibition and (episodic) memory provides a useful model of AH, which
      can accommodate many of the characteristic features of the symptom and fits well
      with the neuroanatomical circuitry that is believed to underlie the occurrence of
      AH.

PMID- 16571457
TI  - Visual search irregularities in schizophrenia depend on display size switching.
AB  - INTRODUCTION: In past research it has been demonstrated that when performing a
      visual search task with either one or multiple (4, 7 or 10) stimuli displayed,
      patients with schizophrenia demonstrate slow response times (RTs) in the display
      size of one, target-absent (one-absent) condition. The goals of the present
      investigation were to replicate this effect, and to gain an understanding of the
      underlying cognitive operations by comparing display-size switch to display-size
      repeat trials. METHODS: In two experiments, patients and controls performed a
      visual search task with either one or four stimuli displayed. In Experiment 1
      (one block with mixed switch and repeat trials), RT for display-size switch
      trials was compared to RT from display-size repeat trials. In Experiment 2, the
      display-size one and display-size four conditions were run in separate,
      homogeneous blocks. RESULTS: The results demonstrate that the one-absent slowing
      effect was eliminated on repeat trials, regardless of whether the switch and
      repeat trials were mixed or presented in separate blocks. CONCLUSIONS: This set
      of results suggests that a combination of cueing and switching effects may
      underlie the one-absent slowing observed in patients, such that switching to the
      one-absent condition is difficult due to insufficient cueing of the relevant
      cognitive operations. This visual search paradigm is an excellent candidate for
      inclusion in the development of a neurocognitive profile specific to
      schizophrenia.

PMID- 16571459
TI  - A combined clinical, neuropsychological, and neuroanatomical study of adults with
      high functioning autism.
AB  - INTRODUCTION: Three hypotheses concerning associations between neuroanatomical
      abnormalities, neuropsychological impairments, and the behavioural manifestations
      of autism were investigated. The primary hypothesis was that the social
      interaction impairments diagnostic of autism are associated with deficits of
      socioemotional perception and abnormalities of the amygdala. One subsidiary
      hypothesis was that the learning and language impairments that occur in less able
      individuals with autism are associated with impaired memory, and with
      abnormalities of hippocampal regions. A second subsidiary hypothesis was that the
      repetitive behaviour diagnostic of autism is associated with executive deficits
      and with abnormalities of the prefrontal cortex. Associations between the
      neuroanatomical regions investigated were also examined. METHODS: Ten adult males
      with high functioning autism (HFA) were compared with 10 healthy controls matched
      for age, sex, verbal and nonverbal ability. Hypothesis-driven structural MRI and
      neuropsychological tests were used to collect neuroanatomical and
      neuropsychological data on all subjects. A version of the Wing Autism Diagnostic
      Interview Checklist was used to collect clinical data on the HFA subjects.
      RESULTS: Strong convergent evidence in support of the amygdala hypothesis was
      obtained, and preliminary support for the hippocampal/parahippocampal hypothesis.
      No clear evidence was obtained in support of the prefrontal hypothesis. Patterns
      of associations amongst volume measures within and between medial temporal and
      prefrontal regions suggest stronger within-region and weaker between-region
      associations in the HFA group compared with controls. CONCLUSIONS: These findings
      are discussed in terms of a model of autism in which selective abnormalities of
      the amygdala and hippocampus (in all cases) and of the parahippocampal gyrus (in
      lower functioning cases) are implicated, and in which a disruption of coordinated
      limbic and prefrontal activity may be critical.

PMID- 16571460
TI  - Effects of stimulus structure and target-distracter similarity on the development
      of visual memory representations in schizophrenia.
AB  - INTRODUCTION: In a previous study (Silverstein, Bakshi, Chapman, & Nowlis, 1998a,
      Cognitive Neuropsychiatry) we demonstrated that while schizophrenia patients
      showed similar learning curves as nonpatient controls when determining whether a
      configural pattern of elements has been seen before or not, they did not
      demonstrate any learning curve with nonconfigural stimuli (in contrast to
      controls). Methodological limitations of that study, however, precluded
      generalisability of those effects. METHODS: In the present study, therefore,
      different groups of schizophrenia patients (n = 18) and controls (n = 22) were
      administered a modified version of the familiarity judgement task used in
      Silverstein et al. (1998a). In the new version of the task: (1) the patterns that
      repeated were different for each participant; and (2) half of the nonrepeating
      patterns were configural and half were nonconfigural. RESULTS: These indicated
      stronger perceptual learning effects for the configural compared to the
      nonconfigural patterns, and overall better performance and more pronounced
      learning effects for the control group. CONCLUSIONS: The data provide further
      evidence for a schizophrenia-related impairment in perceptual organisation and in
      the ability to develop memory representations for novel stimuli.

PMID- 16571461
TI  - Clustering and switching on verbal and figural fluency functions in adults with
      attention deficit hyperactivity disorder.
AB  - INTRODUCTION: Neuropsychological studies of adult patients with ADHD have
      revealed marked disturbances of executive functions including impairments of
      attention, working memory, impulsivity, shifting, and divergent thinking.
      Phonemic fluency tasks, in particular, have been shown to be sensitive measures
      for the assessment of executive functions of adults with ADHD. METHODS: The
      present study has examined figural fluency and both phonemic and semantic verbal
      fluency in 34 adult patients with ADHD and 34 healthy participants. For
      evaluation of fluency performance the number of words or designs, the number of
      repetitions and the number of deviations from test rules were calculated.
      Furthermore, clustering strategies and switching responses were analysed. In
      comparison with healthy participants, patients with ADHD produced significantly
      fewer words or designs, but they did not differ from healthy participants in the
      number of repetitions or rule violations. RESULTS: Analysis of switching and
      clustering showed that patients produced significantly fewer switching responses
      on both verbal fluency tasks, although patients tended to generate smaller
      clusters. Switching on the figural fluency task was unimpaired. CONCLUSIONS: The
      results of the present study suggest that adult patients with ADHD may suffer
      from a dysfunction that may affect retrieval processes and the categorisation of
      knowledge.

PMID- 16571462
TI  - Theory of mind in schizophrenia: a critical review.
AB  - INTRODUCTION: Frith's (1992) neuropsychological theory of schizophrenia posits a
      number of fundamental cognitive impairments underpinning the characteristic
      symptoms of this disorder. One of these is an impairment in the ability to
      correctly interpret and predict the mental states of other people, so-called
      theory of mind (ToM). There is already a substantial body of evidence that ToM is
      impaired in people with schizophrenia. Our aim was to critically review this
      literature. METHOD: A narrative review of the research literature was completed.
      Electronic searches of both Medline and PsycInfo were conducted to locate
      relevant articles. The bibliographies of relevant articles were scrutinised and
      in some cases researchers were contacted directly. RESULTS: A total of 30 studies
      that all examined some aspect of ToM in people with schizophrenia were located.
      These were summarised and key issues on this topic were identified. CONCLUSIONS:
      There is considerable evidence that ToM is impaired in people with schizophrenia.
      However, this is perhaps the only unequivocal finding on the topic to date.
      Issues that demand further clarification include: Is the deficit a state or a
      trait? How to measure ToM in schizophrenia research, and whether certain symptoms
      or groups of symptoms are associated with the ToM deficit. These issues are
      considered and the evidence evaluated. Some priorities for future research are
      suggested.

PMID- 16571463
TI  - Inverse relation between clinical distractibility and Stroop interference in
      functional psychoses.
AB  - INTRODUCTION: Many patients with psychotic disorders appear distractible. Some
      theories propose that distractibility causes psychotic symptoms, others propose
      the reverse. We tested these theories by assessing relations between psychotic
      symptoms, Stroop interference, and clinical distractibility in patients with
      schizophrenia or affective psychoses. METHODS: We rated clinical distractibility
      in patients with acute schizophrenia or affective psychoses and measured their
      Stroop interference in a single trial colour-naming task. RESULTS: Clinical
      distractibility related inversely to Stroop interference. Stroop interference was
      small in drug-naive patients with schizophrenia, but normal in those receiving
      treatment. Patients with affective psychoses showed the opposite pattern.
      CONCLUSIONS: The abnormality of attention that clinicians rate as
      "distractibility" is probably the opposite-attentional capture. Abnormal
      attention neither results from nor causes psychotic symptoms. Rather, it is an
      independent correlate of pathophysiology in functional psychoses that merits
      assessment and treatment in its own right.

PMID- 16571464
TI  - "Sleights of mind": delusions, defences, and self-deception.
AB  - Two different modes of theorising about delusions are explored. On the one hand
      is the motivational approach, which regards delusions as serving a defensive,
      palliative, even potentially adaptive function. On the other, is the cognitive
      deficit approach, which conceptualises delusions as explicitly pathological,
      involving abnormalities in ordinary cognitive processes. The former approach,
      prominently exemplified by the psychoanalytic tradition, was predominant
      historically, but has been challenged in recent years by the latter. Some
      grievances against psychoanalytic theory are briefly discussed, and it is argued
      that although the reasons for psychoanalysis falling into scientific disrepute
      are partly justified, the psychodynamic notion that motivation has access to the
      mechanisms of belief formation is of potentially crucial theoretical utility. A
      variety of possible syntheses of the two theoretical modes are therefore
      explored, in the belief that the most comprehensive account of delusions will
      involve a theoretical unification of both styles of explanation. Along the way,
      an attempt is made to locate the notions delusion, defence, and self-deception in
      a shared theoretical space.

PMID- 16571465
TI  - You must be looking at me: the nature of gaze perception in schizophrenia
      patients.
AB  - INTRODUCTION: Accurately identifying gaze direction is an important component of
      successful social interaction. Preliminary research indicates that schizophrenia
      patients have deficits in gaze perception, but the nature of this deficit is
      still unclear. The current study investigates whether nonspecific perceptual
      abnormalities could explain gaze perception deficits and whether schizophrenia
      patients show a direct gaze bias in their judgement. METHODS: Fifteen chronic
      schizophrenia patients and nineteen normal control participants made a direct
      gaze judgement for eyes in a face, and a centre judgement for a geometric shape
      in a scrambled face. RESULTS: The data show that schizophrenia patients are as
      accurate as healthy control subjects at identifying direct gaze when it occurs
      but they are more likely to misinterpret averted gaze as directed at them. The
      pattern of results indicates that this tendency to endorse direct gaze is not a
      consequence of a perceptual deficit in judging angular displacement. CONCLUSIONS:
      Schizophrenia patients have a self-referential bias in judging the direction of
      gaze that could lead to the misinterpretation of another person's intentions
      during the course of social interaction.

PMID- 16571466
TI  - Symptomatology and social inference: a theory of mind study of schizophrenia and
      psychotic affective disorder.
AB  - INTRODUCTION: There is evidence that certain patients with schizophrenia have
      deficits in theory of mind (ToM) capabilities. It is, however, unclear whether
      these are symptom or diagnosis-specific. METHODS: A ToM hinting task was given to
      15 patients with a DSM-IV diagnosis of schizophrenia, 15 patients with affective
      disorder and 15 healthy controls. Severity of the current psychopathology was
      measured using the Krawiecka standardised scale of psychotic symptoms (Krawiecka,
      Goldberg, & Vaughan, 1977); IQ was estimated via the Ammons and Ammons Quick Test
      (Ammons & Ammons, 1962). RESULTS: The group with schizophrenia performed
      significantly worse than the affective and control groups. Poor performance on
      the hinting task was found to be significantly related to the presence of
      positive symptoms (instead of negative ones) and specifically related to
      delusions and hallucinations. These findings remained when covariance for
      potentially confounding variables was applied. CONCLUSIONS: Individuals with high
      levels of delusions and hallucinations performed significantly worse on this ToM
      task, regardless of diagnosis, implying ToM impairment is not exclusive to
      schizophrenia but is evident in other forms of psychosis. Between-group analyses
      showed the schizophrenia group had a significantly poorer performance on this
      task than the others.

PMID- 16571468
TI  - The impact of clinical depression on working memory.
AB  - INTRODUCTION: Both Channon, Baker, and Robertson (1993) and Hartlage, Alloy,
      Vazquez, and Dykman (1993) claim that working memory impairment in depressed
      patients is limited to Baddeley's (1996) central executive and does not affect
      either the phonological loop or the visuospatial scratchpad. Our key questions
      were: (1) is there an impairment of working memory in depression and which
      elements does it effect; (2) is another major clinical group also affected and in
      what ways, and finally, (3) how do these groups vary when compared with each
      other and with normals? Thus we sought to locate a depression-specific effect and
      define its extent. METHODS: We tested 35 depressed patients, using both 24
      anxiety patients and 29 normal controls as comparisons. Several tasks were used
      so that we could differentiate between the three key aspects of working memory.
      RESULTS: Contrary to Channon et al., we found that depression affects the
      allocation of attention and all elements of working memory. The depression group
      showed a distinct performance profile, with impairments occurring on measures of
      both the phonological loop and visuospatial sketch pad. On measures of central
      executive functioning, both depression and anxiety groups showed comparable
      levels of impairment when compared with the control group. CONCLUSIONS: We
      propose that the source of general disruption in both depressed and anxious
      patients may be a competition between attempts to direct attentional resources to
      the task in hand and away from the distractive and intrusive effects of automatic
      negative thoughts.

PMID- 16571467
TI  - Neuropsychological deficits, syndromes, and cognitive competency in
      schizophrenia.
AB  - INTRODUCTION: Neuropsychological functioning connects neuropathology and symptoms
      in schizophrenia. Previous work suggests that deficient initiation and inhibition
      underlie the psychomotor poverty and disorganisation syndromes, respectively.
      Furthermore, although the syndromes are associated with impairments in everyday
      functioning, cognitive competency (CC; cognitive skills for independent living)
      has been neglected as an outcome. This study tested a three-level model of
      schizophrenia pathology (Neuropsychological dysfunction --> Syndromes --> CC),
      using unstructured neuropsychological tasks to measure initiation and inhibition.
      METHODS: Participants were 40 adults with schizophrenia. A verbal picture
      description and the Tinkertoy test yielded initiation and inhibition measures
      with good interrater reliability. Symptoms were rated using the SANS and SAPS,
      and an insight scale was administered. The Cognitive Competency Test utilised
      simulated situations to assess CC. RESULTS: Initiation failed to predict
      psychomotor poverty, but affected CC directly. Only one indicator of
      disinhibition (intermingling of personal material into speech) predicted
      disorganisation, which, through mediation, led to CC deficits. Insight correlated
      with disorganisation and contributed to CC. Unique effects of initiation,
      disorganisation, and insight, combined, explained 58% of CC variance.
      CONCLUSIONS: Partial support for the three-level model was obtained. Specific
      neuropsychological abilities and symptoms explain a substantial proportion of the
      variance in cognitive competency.

PMID- 16571469
TI  - Editorial.

PMID- 16571470
TI  - Delusions demand attention.
AB  - We used a variant of the Stroop paradigm to investigate attention bias in a young
      woman (JK) with delusional beliefs that she had died and that members of her
      family had changed. JK was shown sets of words printed in different colours of
      ink, and was asked to name the colour of each word. Sets of words were chosen
      which related to her delusions, and to possible contributory moods. The times
      taken by JK to colour-name words in these lists were compared with her times to
      colour-name sets of neutral words. There were three separate testing sessions
      which took place over a two-year period. In comparison to her times to name the
      colours of words in the neutral lists, JK was significantly slower to colour-name
      test lists containing words related to her delusional beliefs. When she was no
      longer experiencing these delusions, however, she was no slower to colour-name
      any of the test word lists. The results indicate that the Stroop paradigm can be
      useful in investigating individual cases of delusions and in monitoring changes
      in attentional bias over time.

PMID- 16571471
TI  - Resolution of left hemisphere cognitive dysfunction in multiple sclerosis with
      magnetic resonance correlates: a case report.
AB  - Cognitive impairment is common in multiple sclerosis and although deterioration
      has been observed in individual patients at the time of relapse, improvement in
      cognitive function in parallel with remission of neurological impairment has
      proved more difficult to document. We describe a 21-year-old women with a one
      year history of relapsing remitting multiple sclerosis, who was admitted to
      hospital following a severe relapse which rendered her quadriplegic. Detailed
      psychometric assessment was carried out during relapse and on recovery of
      neurological function, eight weeks later. There were improvements in arithmetic,
      naming, and comprehension tasks. The patient had T2 weighted and gadolinium
      enhanced magnetic resonance imaging and magnetic resonance spectroscopy. These
      showed a reduction in lesion size, lesion enhancement, and changes in brain
      chemistry which parallel the improvement in cognitive performance.

PMID- 16571473
TI  - Discourse connectedness in manic and schizophrenic patients: associations with
      derailment and other clinical thought disorders.
AB  - The language performance of hospitalised manic ( n = 12) and schizophrenic (n=15)
      patients was compared in order to test hypotheses based on previous models of
      communication disorder in these patient groups. It was hypothesised that the
      derailments of manic and schizophrenic patients were discriminable by virtue of
      differences in the level of connectedness of the speech during this type of
      language disorder. Previous hypotheses have suggested that manics derail because
      they discuss multiple concurrent topics and schizophrenics derail as a pattern of
      general vagueness and poorly interconnected speech. These hypotheses were
      supported by the finding that manic patients manifested a higher level of overall
      discourse connectedness during derailments, even when the overall increased
      amount of speech was accounted for. Manics were not simply more competent
      overall, because they failed to differ from schizophrenics in their discourse
      connectedness during nondisordered segments. These results are discussed in terms
      of their implications for clinical and linguistic differentiation of the language
      of psychotic patients.

PMID- 16571472
TI  - Delusional misidentification of inanimate objects: a literature review and
      neuropsychological analysis of cognitive deficits in two cases.
AB  - Following a brief review of the literature on Delusions of Inanimate Doubles
      (DID), compared with other similar delusions, two cases are presented. Each
      completed a battery of tests designed to explore their cognitive abilities. In
      both cases, familiar and unfamiliar face-processing skills remained intact and
      word memory was unaffected. Their abilities to identify famous buildings and
      recognise unfamiliar houses were impaired. We propose that an extension of Ellis
      and Young's (1990) account of Capgras delusion can explain the cognitive
      impairments in case of DID. A comparison of the hypotheses of Staton et el.
      (1982), Ellis and Young (1990), and Van Lancker (1991) is also made. The last two
      have obvious similarities and seem to provide the best general approach. Finally,
      we caution the need to consider how a mood of suspiciousness may be needed to
      distort attribution processes that sustain delusional thinking.

PMID- 16571474
TI  - Are children with autism deaf to gricean maxims?
AB  - Department of Psychology, Birkbeck College, University of London, UK High
      functioning children with autism show a severe deficit in the development of
      pragmatics whereas their knowledge of syntax and morphology is relatively intact.
      In this study we investigated further their selective communication impairment by
      comparing them with children with specific language impairment (SLI) and normally
      developing children. We used a pragmatic task that involved the detection of
      utterances that violate conversational maxims (avoid redundancy, be informative,
      truthful, relevant, and polite). Most children with autism performed at chance on
      this task, whereas all children with SLI and all normal controls performed above
      chance. In addition, the success of children with autism on the pragmatics task
      was related to their ability to attribute false beliefs. These results are
      consistent with the idea that communication deficits in autism result from a
      selective impairment in representing propositional attitudes. Their implications
      for domain-specific views of cognitive development are discussed.

PMID- 16571475
TI  - What's inside someone's head? Conceiving of the mind as a camera helps children
      with autism acquire an alternative to a theory of mind.
AB  - A group of children with autism were taught a specific strategy to help them
      solve a series of theory of mind problems. We focused our teaching on the false
      belief task and taught them the analogy that people have photos in their heads.
      This strategy draws on a domain of intact cognition in autism (understanding
      photographic representations) to bypass a cognitive impairment in a certain
      domain (understanding mental state representations). All the children were able
      to understand photographic misrepresentation during teaching and, following
      specific teaching, they could use the strategy of visualising photos in
      characters' heads to predict the character's behaviour. In contrast, none of the
      children could use the photo strategy to predict a character's mental states. The
      educational and theoretical implications of this study are discussed.

PMID- 16571476
TI  - Editorial: neural systems and psychiatric disorders.

PMID- 16571477
TI  - Attention and schizophrenia: a view from cognitive neuroscience.

PMID- 16571478
TI  - Visual processing in patients with Fregoli syndrome.
AB  - We investigated four paranoid schizophrenic patients diagnosed with Fregoli
      delusion, and four matched psychotic controls. Neuropsychological testing
      included visual and verbal recognition memory, in addition to a comparison of
      left and right hemispheric processing of two different classes of stimuli,
      animate and inanimate objects. Performance on the recognition memory test failed
      to discriminate between the two psychotic groups on the basis of facial
      recognition, however, the patients with Fregoli delusion failed to show the right
      hemisphere processing advantage for the animate class of stimuli found for the
      set of norms and also present in the psychotic control group. These results are
      discussed in the context of both current theories of the delusional
      misidentification syndromes in general, and models of facial recognition in
      particular.

PMID- 16571479
TI  - Do I really look like that?

PMID- 16571480
TI  - "Mirror, mirror on the wall, who...?": towards a model of visual self
      recognition.
AB  - Self-recognition and self-awareness are processes fundamental to human
      development. This report describes the case of an 80-year-old woman who
      demonstrated the ''mirror sign'', an inability to recognise the reflection of
      oneself in a mirror. An attempt has been made to provide a cognitive
      neuropsychological explanation for this profound impairment in visual self
      recognition, incorporating current cognitive theories of delusion formation and,
      specifically, delusions involving distorted appreciation of the self or others.
      We speculate that the impairment in visual self-recognition arises from deficits
      in visual and personal semantic memory related to bilateral hippocampal lesions,
      and that the greater extent of impairment in visual self-recognition compared
      with that for other familiar persons is possible evidence for a specific self
      recognition process, represented as a separate ''self-identity node'' in the
      current face-processing model of Bruce and Young (1986).

PMID- 16571481
TI  - Brief report: bradyphrenia in Parkinson's disease, Huntington's disease, and
      schizophrenia.
AB  - The current paper assessed bradyphrenia, or slowed thinking, in patients with
      Parkinson's disease, Huntington's disease, and schizophrenia using a modified
      planning measure designed to maximise the demands on cognitive processing.
      Findings indicated normal performance in schizophrenia but prolonged thinking
      time in Parkinson's disease and, to a lesser degree, Huntington's disease and a
      relationship between thinking time and task complexity.

PMID- 16571484
TI  - Editorial cognition, neurology, psychiatry: golden triangle or bermuda triangle?
AB  - Cognitive neuropsychiatry occupies the comparatively neglected research region
      that lies between neurology, psychiatry, and cognitive psychology. Reasons for
      this neglect are discussed, together with arguments as to why it may be timely to
      focus on this intellectual no man's land.

PMID- 16571485
TI  - Syntactic complexity and negative symptoms in first onset schizophrenia.
AB  - This paper compares the syntactic features of three groups of subjects: first
      onset schizophrenics with negative symptoms (n=17); with no negative symptoms
      (n=18); and nonpsychiatric controls (n=16). The speech of schizophrenic subjects
      contained more syntactically and semantically deviant sentences. The negative
      symptom group produced shorter sentences that contained lower levels of clausal
      embedding. Most of these differences were related to group differences in social
      class, attentional deficits in the schizophrenic group, or collinearity between
      sentence length and clausal complexity. Despite this, the difference in clausal
      complexity persisted after the effects of these confounding variables had been
      removed. This indicates that reduced syntactic complexity is an important feature
      of the speech of patients in whom negative symptoms are prominent. The
      significance of this finding is discussed in relation to recent theories of
      schizophrenia.

PMID- 16571486
TI  - Psychotic experiences induced in deluded patients using distorted auditory
      feedback.
AB  - The effect of hearing immediate auditory feedback of their own voice distorted in
      pitch was examined in 21 patients with a diagnosis of schizophrenia. Patients
      frequently reported that they heard a voice "speaking when I speak" and often
      attributed this "other" voice to an external agent: "I think it's an evil spirit
      speaking when I speak." The frequency of making these ''other''attributions was
      significantly related to degree of pitch distortion (rho = 0.62, P <.01) and to
      current severity of delusions (rho = 0.62, P <.01). However, the relationship
      with hallucinations was not significant (rho = 0.40) and there was no
      relationship with negative features such as psychomotor retardation. We conclude
      that the "hallucination-like" reports elicited by our paradigm resulted from an
      interaction between an unusual perceptual experience (distorted auditory
      feedback) and an abnormal mechanism for belief formation present in deluded
      patients. This formulation suggests a close relationship between delusions and
      hallucinations.

PMID- 16571487
TI  - "Depressive Realism" assessed via Confidence in Decision-making.
AB  - There are two currently influential views regarding the link between cognitive
      distortions and depression. The first states that depressed individuals perceive
      the world and themselves with a strong negative bias or distortion, and that
      mentally healthy individuals perceive the word with relative accuracy. The second
      ''depressive realism'' camp argues that healthy individuals are positively biased
      and the depressed are relatively unbiased and hence, more realistic. In the
      present investigation, subjects suffering from major depression, subjects
      recovered from major depression, and a group of healthy controls were examined
      with regard to their confidence in answering each of 99 general knowledge
      questions. Confidence ratings were analysed separately according to correct or
      incorrect responses. There were no significant differences in performance (i.e.
      accuracy of answer between the three groups). When answering correctly, depressed
      subjects were significantly less confident than healthy control subjects. On
      answering incorrectly, none of the three groups were significantly different in
      their confidence ratings. These findings support the cognitive distortion view of
      depression and provide no evidence of ''depressive realism''.

PMID- 16571488
TI  - Anosognosia for hemiplegia: patient retrospections.
AB  - Various competing hypotheses have been put forth to explain how it is possible
      for patients to be unaware of their own profound weakness. We investigated
      whether patients' retrospections after resolution of their anosognosia along with
      their clinical features are consonant with these hypotheses. Three well-educated
      and articulate men were interviewed about their stroke and their subsequent
      awareness of weakness. Psychological denial, general cognitive impairment, a
      faulty superordinate awareness system, lack of knowledge of stroke symptoms, and
      minimal curiosity as a personality trait were not satisfactory explanations for
      their anosognosia. Their self-observations and clinical presentations suggest
      that: (1) anosognosia for hemiplegia can be exquisitely domain-specific; (2)
      weakness, rather than being perceived automatically, must be discovered; (3)
      discovery of weakness is impeded by a feedforward intentional deficit which
      probably interacts with notions of ''body schema'' in complex ways; and (4)
      awareness of deficit emerges in a graded fashion.

PMID- 16571489
TI  - Can PTSD Occur with Amnesia for the Precipitating Event?
AB  - Theoretical accounts of post-traumatic stress disorder (PTSD) suggest that memory
      for a precipitating event is crucial for its development. Indeed, Sbordone and
      Liter (1995) have recently argued that mild traumatic brain injury and PTSD are
      mutually exclusive disorders. A case is described who sustained a severe head
      injury in a road traffic accident. He had a retrograde amnesia of two days and a
      post-traumatic amnesia of four weeks. Six months after his accident he was found
      to be suffering from a number of anxiety symptoms, including nightmares and
      intrusive thoughts, consistent with a diagnosis of PTSD. The implications of this
      case for theories of PTSD are discussed.

PMID- 16571490
TI  - A study of recovery of memory function in a case of witnessed functional
      retrograde amnesia.
AB  - We describe a case of transient functional retrograde amnesia that had features
      of a fugue state, and that was accompanied by loss of personal identity and
      significant autobiographical amnesia. Uniquely, we were able to gather
      information from witnesses who observed the episode from its onset, and we were
      also able to monitor the acute stages of recovery of memory function over the
      subsequent four-week period. The profile of memory loss was characterised by
      impaired performance on both autobiographical and public events memory tasks, in
      the context of normal anterograde memory test scores. Shrinkage of retrograde
      amnesia took place over a four-week period, with autobiographical and public
      events components of retrograde memory recovering at the same rate. We discuss
      the possible role of unconscious processes underlying the episode, as compared to
      conscious simulation. We argue that most cases of functional retrograde amnesia
      may represent a combination of conscious simulation and unconscious processes.

PMID- 16571491
TI  - Opinion: reflections on cognitive neuropsychiatry.

PMID- 16571492
TI  - At the centre of a science of psychopathology? Characteristics and limitations of
      cognitive research.
AB  - In this brief paper I will suggest that the cognitive approach has four
      characteristics which must place it at the centre of any complete science of
      psychopathology: (1) it leads to testable hypotheses about abnormal mental
      states; (2) it establishes a link between normal psychology and abnormal mental
      processes, and therefore obviates the need to dichotomise behaviour into the
      normal and the abnormal; (3) it has the potential to make apparently bizarre and
      irrational behaviour understandable; and (4) it is neutral with regard to the
      relative contributions that biology and the environment make to the aetiology of
      psychiatric disorders. I also identify three limitations of contemporary
      cognitive models of psychiatric disorders: (1) an over-reliance on conventional
      methods of psychiatric classification; (2) an underemphasis on social aspects of
      cognition; and (3) a failure to integrate findings obtained from different
      models. Once these limitations are overcome, cognitive research is likely to lead
      to a revolution in our understanding of abnormal behaviour.

PMID- 16571493
TI  - What's wrong and what's right in neuropsychology and neuropsychiatry.
AB  - There has been a recent converging of interests by psychiatrists and
      psychologists in subjective mental phenomena. Examples of topics where these
      converging interests arise include the relationship of confabulation and
      delusional memories, the nature of face-processing deficits in prosopagnosia and
      the Capgras delusion, and hierarchial models of psychological function. These
      developments are very much welcomed; but the over-interpretation of
      neuropsychological test findings in neuropsychiatry, and the occasional failure
      to take account of clinical context (particularly the psychiatric background) in
      neuropsychology, are also noted. Cognitive neuropsychiatry appears to have
      emerged as a label to identify this converging of interests, modelling itself on
      cognitive neuropsychology. The potential benefits and limitations of such an
      approach are discussed.

PMID- 16571494
TI  - Opinion cognitive markers for neuropsychiatry?

PMID- 16571496
TI  - Cognitive neuropsychiatry and delusional misidentification syndromes: an
      exemplary vindication of the new discipline.

PMID- 16571495
TI  - Schizophrenia and autism considered as the products of an agnosic right shift
      gene.
AB  - Crow (1995a) has argued that schizophrenia is caused by a gene associated with
      the evolution of human language and cerebral specialisation. This paper suggests
      a mechanism for Crow's theory which requires only one new assumption for the
      right shift genetic model of handedness and cerebral dominance (Annett, 1978).
      The proposal is that the RS+ allele, whose normal function is to induce the left
      hemisphere to serve speech by impairing speech-related cortex in the right
      hemisphere, tends to lose its directional coding. It becomes agnosic (RS+ a) for
      right versus left and impairs the left or right hemisphere at random.
      Schizophrenia is likely to develop when the RS+ a gene is paired with a normal
      RS+ gene but only in the 50% of cases where both hemispheres are affected. In the
      50% where RS+ a affects the right hemisphere, development is normal as in the RS+
      RS+ genotype. The risks for schizophrenia in monozygotic and dizygotic twins and
      other relatives are as expected for 50% expression of a Mendelian gene which is
      paired with a particular allele, but not alternative alleles at the same locus.
      The frequency of homozygotes for the agnosic gene is about 4 in 10,000, the rate
      observed for autism. A random pattern of double hemisphere deficits would give
      scope for a range of developmental strengths and weaknesses as observed within
      the spectrum of autistic disorders. Tests of the model require brain-imaging
      studies sensitive to individual differences in hemisphere lateralisation and a
      search for a genetic locus with human and nonhuman primate alleles, together with
      a mutant of the human form with a frequency of about 2%.

PMID- 16571497
TI  - A meta-analytic review of Wisconsin Card Sort studies in schizophrenia: general
      intellectual deficit in disguise?
AB  - A majority of studies show that schizophrenics perform poorly on so-called tests
      of executive or frontal lobe function--the paradigmatic case being the Wisconsin
      Card Sort Test (WCST). Nevertheless, the specific character of this deficit in
      schizophrenia remains underspecified. In particular, it seems premature to assume
      that schizophrenia is characterised by an executive dysfunction and/or a disorder
      of frontal lobe function before determining whether any deficit is: selective;
      disproportionate to the general level of intellectual functioning; or
      qualitatively comparable with that of frontal lobe patients. A meta-analysis was
      conducted on 29 studies comparing the performance of schizophrenics and normal
      controls on the WCST. This showed that the mean weighted effect size was large
      for categories achieved (d = 0.91), medium for absolute level of perseveration (d
      = 0.53), but only small for the proportion of perseverative errors (d = 0.18). By
      contrast, the effect size for Wechsler Adult Intelligence Scale Intelligence
      Quotient (WAIS IQ) in a subset of these studies (d = 1.23) was significantly
      larger than for any WCST measures. This pattern of findings challenges notions
      that schizophrenia is characterised by an executive dysfunction that is:
      selective; disproportionate to IQ level; and analogous to that found in frontal
      lobe patients. Rather, the poor WCST performance of schizophrenics appears to
      reflect a generalised intellectual deficit.

PMID- 16571500
TI  - Evidence for changed recognition of emotionally charged words in patients with
      Gilles de la Tourette syndrome and obsessive compulsive disorder.
AB  - Patients with Gilles de la Tourette syndrome (TS) frequently show obsessions and
      compulsions. Pathophysiologically, TS has been linked to abnormalities of the
      basal ganglia and forebrain which are related to emotional processes. Because
      recordings of event-related potentials (ERPs) have shown that the emotional
      content of words interacts with the subjects' ability to recognise repeated words
      we hypothesised that patients who were diagnosed to have TS and obsessive
      compulsive disorder (OCD) utilised a changed cognitive process for the
      recognition of emotional words. ERPs were recorded while 12 patients and matched
      control subjects viewed a series of emotionally neutral, negative, and positive
      words. These were repeated after some intervening items with the task being to
      discriminate between new words and repeated words. In both groups, correctly
      detected repeated words showed a more positive ERP waveform than new words
      between 350 msec and 550 msec after stimulus presentation. Although we found no
      group difference of this old-new effect for emotionally neutral words, patients
      had a smaller effect than control subjects for negative and positive words. This
      finding is discussed with respect to the literature and is viewed as evidence for
      changed memory mechanisms for emotionally charged words in patients with TS and
      OCD.

PMID- 16571501
TI  - Autonoetic awareness, executive social skills, and the appreciation of intention:
      figurative reasoning in amnesia, confabulation, and schizophrenia.
AB  - This paper presents a cognitive neuropsychological model of the appreciation of
      unfamiliar abstract speech. The model elaborates upon the proposals of Bottini et
      al. (1994) by suggesting that we come to appreciate unfamiliar metaphorical
      speech in the autonoetically aware state. The specific executive skills of (1) an
      "as if" processor (2) a shared relevance seeker and monitor are harnessed to
      retrieval of information from personal long-term memory or imagination. The same
      cognitive system is assumed to handle other forms of indirect speech which need
      disambiguation as well as situations in which the intention or belief state of
      another has to be inferred. Predictions concerning the behavioural consequences
      of malfunctions occurring at different stages within the system are set out.
      METHOD: To illustrate the behavioural consequences of differential system
      dysfunction, data collected from four case studies are presented. Each case
      performed two tasks. These entailed the appreciation of true/false functional
      sentences and unfamiliar metaphors. The sentences both required the need to
      reason analogically and were matched for syntactic complexity and number of
      words. RESULTS: Clear similarities were seen in the performance of the new
      metaphors test between a patient with Korsakoff syndrome and consequent amnesia
      and one with negative feature schizophrenia. The same test also highlights
      similar processing deficits in a case of Korsakoff syndrome with amnesia and
      confabulation and a schizophrenic patient with formal thought disorder. By
      proposing different loci for system malfunctions within and across diagnoses the
      characteristic clinical and/or cognitive features of the illnesses or syndromes
      are addressed. The importance of recognising the implications of specific
      cognitive dysfunctions across diagnoses for understanding the cognitive profiles
      of individual cases and the clinical aspects of the illness/syndrome is stressed.
      Finally, the utility of the model for explaining how we process other situations
      that require an appreciation of others' intentions, thoughts, and beliefs is
      discussed.

PMID- 16571502
TI  - Measuring IQ in schizophrenia research: an update of the Quick Test in estimating
      IQ decline.
AB  - The WAIS-R measurement of IQ in schizophrenic patients is problematic: the Quick
      Test of Ammons and Ammons has been used as an alternative despite variability in
      the accuracy of its estimation of IQ in other groups. We have updated the Quick
      Test and compared our new version with the original in 44 schizophrenic patients,
      and both versions with the WAIS-R in a subgroup of 15 patients. Improving the
      Quick Test materials led to improvement in performance independent of long-term
      memory function: both versions overestimated WAISR IQ. A previous finding of very
      high correlation between WAIS-R IQ and Quick Test IQ estimate in schizophrenic
      patients was not replicated. IQ decline measured with the NART and the Quick Test
      was less than that using the NART and the WAIS-R. We conclude that the Quick Test
      has serious limitations as an estimate of IQ in schizophrenic patients, and will
      bias the assessment of IQ decline so that its extent is apparently less than in
      reality.

PMID- 16571503
TI  - Vigilance in schizophrenia and its disruption by impaired pre-attentive
      selection: a dysintegration hypothesis.
AB  - INTRODUCTION: The study determined, simultaneously, whether major deficits of
      schizophrenia (sustained and selective attention, slow information processing,
      slow motor responding) are independent or related to each other. METHODS: An
      auditory vigilance task (Pigache Attention Task, PAT) required a button-press to
      targets during four 5-minute subtests (slow diotic, fast diotic, slow dichotic,
      fast dichotic, analogous to four versions of the continuous performance test).
      Twenty schizophrenics on the first test-occasion of a double-blind, placebo
      controlled, crossover study were compared to 11 healthy subjects. Also, all 28
      fortnightly test occasions were analysed to quantify the schizophrenia deficits
      more precisely and the PAT was evaluated in a larger group of 86 healthy
      subjects. RESULTS: Schizophrenics were significantly impaired on all task
      parameters versus healthy subjects. The patients' errors were independent and
      additive (grand mean components: basic task 36%, including a 9% time-on-task
      component; speed increment 26%; dichotic increment 38%). Errors, latencies, and
      psychosis severity were mutually correlated. CONCLUSIONS: The performance of all
      subjects confirmed a quantitative Vigilance Decision Model. The PAT impairments
      in schizophrenia suggested that rival options (e.g. thoughts) redeployed or
      suppressed attention away from the task , indicating a dysfunction of pre
      attentive selection processes. Brain mechanisms are discussed and a new dys
      integration hypothesis of schizophrenia is proposed.

PMID- 16571504
TI  - Mind and action.
AB  - The author argues that Cutting's Principles of psychopathology (1997) is a
      remarkable compendium of ideas on psychopathology and philosophy, and offers a
      valuable resource for those interested in this area. There is, however, a marked
      contrast between the way in which Cutting views philosophy (as a source of ideas)
      and the way contemporary philosophy views itself (as being about the skills of
      deepening understanding and arriving at original ideas through the application of
      analytical and critical thinking skills). In addition, Cutting's survey of the
      philosophy literature is highly selective and is concentrated largely on pre
      World War II philosophy. As a result of both these features, the book
      underemphasises the potential value of philosophy for psychopathology. It is
      argued in this paper that philosophy provides strategies for inquiry into the
      nature of the mind and its pathologies, rather than being merely a source of
      ideas. This point is made in more detail by exploring the contrast between the
      approach Cutting adopts and the approach used by both Karl Jaspers and in recent
      work on the philosophy of psychopathology, specifically K.W.M. Fulford (1989).
      Although the author of this paper is entirely in agreement with Cutting's general
      view (that psychopathology is underpinned by philosophy), it is argued that he
      does not take his exploration far enough to extract from his survey the
      fundamental underlying implications for psychopathology-that psychopathology is
      inherently evaluative and normative in its stance, but that this aspect is
      rendered opaque, currently, by psychopathology's status as an empirical science.

PMID- 16571505
TI  - Conversion hysteria: is it a viable concept?
AB  - The notion of conversion hysteria is built around three assumptions to the effect
      that symptoms can arise without an adequate pathological base, that the patient
      experiences these symptoms as ''real'' in that they are not consciously feigned,
      and that psychological distress can be transformed or ''converted'' into physical
      symptoms. It is argued that the first of these assumptions is valid and that the
      truth of the second cannot be judged with adequate reliability to make it
      acceptable as a criterion for classification. The last assumption is questionable
      in that it is difficult to conceive of a satisfactory explanation as to how the
      process of conversion might operate.

PMID- 16571506
TI  - Malingering, hysteria, and the factitious disorders.
AB  - The arguments contained within this paper take as their starting point the
      suggestion that malingering is related along three separate continua to the
      nosological entities of antisocial behaviour, hysteria and the factitious
      disorders. The paper is both an attempt to show how these continua can be
      underwritten and at the same time a discussion of the aetiology of the disorders
      in question. It will be argued that the aetiological accounts of hysteria and the
      factitious disorders found in the psychiatric literature fail to make room for an
      account of the nature of the relationships of these disorders with malingering
      and thereby fail to fulfil the most important constraint on the acceptability of
      explanations in this area. In discussing the factitious disorders in the light of
      this constraint it will be suggested that psychodynamic explanations are vacuous
      and folk-psychological explanations in principle unavailable. With regard to
      hysteria it will be suggested that an explanatory account which embraces all the
      required phenomena and accommodates the close relationship of the disorder to
      malingering must make use of cognitive-psychologically informed account of self
      deception which treats hysterical beliefs as beliefs which are formed as a result
      of a failure to accurately appraise the subjectively available evidence.

PMID- 16571507
TI  - Hysterical paralyses as disorders of action.
AB  - Hysterical paralysis is an unusual diagnosis, requiring the physician to infer
      the intentional stance of the patient when the latter fails to act. This paper
      argues that the distinction between ''hysterical'' and ''feigned'' disorders
      cannot be currently justified on the basis of objective criteria. The physical
      ''signs'' of hysterical paralyses are those of voluntary motor inconsistency. The
      patient fails to perform certain acts, whereas others, utilising the same muscle
      groups, are preserved. Hence, hysterical paralyses are essentially disorders of
      action, themselves the product of abnormalities of mind, ''will'', or the
      intention to deceive (the ''self'' or the ''other''). The role of the
      psychodynamic unconscious in the maintenance of hysterical paralyses is
      problematic; their maintenance requires the patient's conscious attention: They
      remit with sedation and distraction. Although functional neuroimaging studies of
      these symptoms have been preliminary, they may eventually reveal an objective
      pathophysiology of the disordered ''will'', and a contrasting functional anatomy
      of the intentionally feigned symptom.

PMID- 16571508
TI  - Hypnosis and conversion hysteria: a unifying model.
AB  - There are many similarities between the symptoms of conversion hysteria and
      phenomena produced in hypnotic contexts. This paper reviews some of those
      similarities and considers more general features associated with both hypnotic
      phenomena and conversion hysteria symptoms such as lack of concern, perceived
      involuntariness, the display of ''implicit knowledge'' and their apparently
      compliant nature. Neurophysiological and brain-imaging studies of hypnotically
      produced effects and conversion symptoms are described, which implicate frontal
      cortical structures in moderating the respective changes elsewhere in the brain,
      particularly in cingulate cortex. A recurrent theme is the apparent paradox which
      exists between, on the one hand, the subjective reality and involuntariness of
      both hypnotic phenomena and the symptoms of conversion hysteria and, on the
      other, the fact that objectively they appear to be role-congruent enactments
      responsive to the manipulation of motivational factors, expectancy, and social
      influence. A model of consciousness and self-awareness is presented which
      attempts to resolve that paradox whilst describing similar mechanisms underlying
      hypnotic phenomena and conversion hysteria symptoms. The model develops the idea
      of a central executive structure, similar to the notion of a supervisory
      attentional system, acting outside self-awareness but at a late stage of
      information processing which can be directly influenced from both internal and
      external sources to produce the relevant phenomena. The paper ends by proposing
      that as conversion disorder, pain disorder, and the dissociation disorders appear
      to be linked by a common mechanism they should be classified together under the
      heading of auto-suggestive disorder.

PMID- 16571509
TI  - Individual differences in schizotypy and reduced asymmetry using the chimeric
      faces task.
AB  - INTRODUCTION: Recent work in schizophrenia has suggested a reduction in right
      hemisphere processing in patients experiencing first-rank symptoms. Similarly,
      work in individual differences in schizotypal personality traits in the normal
      population has suggested differences in hemispheric processing that may mirror
      results in diagnosed groups. A reduction of attentional asymmetry to the left
      visual field was hypothesised in right-handed males scoring highly on measures of
      positive schizotypy. METHODS: Normal adult subjects completed a questionnaire
      containing five scales of Unusual Experiences, Cognitive Disorganisation,
      Introvertive Anhedonia, Impulsive Nonconformity, and Schizotypal Personality
      Disorder. In the first experiment, subjects made emotional decisions to chimeric
      faces under free viewing conditions. The second experiment was intended to
      replicate the first but used tachistoscopic presentations as well as
      counterbalancing subjects with respect to laterality of response keys. RESULTS:
      Reduction in attentional asymmetry was correlated with scales of positive
      schizotypy in both experiments in males only. In addition, the relationship was a
      dynamic one, developing over time as the attentional asymmetry increased for low
      schizotypal scorers but did not for high scorers. CONCLUSIONS: Together, these
      results suggest that there is a reduction of right hemisphere arousal in some
      individuals possessing a predisposition to experience unusual perceptions that
      echoes similar findings in acute schizophrenics.

PMID- 16571510
TI  - Memory for actions in children with autism: self versus other.
AB  - In order to ask whether autism is associated with difficulty in self-monitoring
      we gave a group of children and adolescents with autism a task in which they
      themselves had to remember whether they or another person had performed certain
      actions. In our first experiment, three groups of participants had to recall
      whether placements of picture cards had been made by themselves or by the
      experimenter. The participants with autism performed at a much lower level than
      the two comparison groups and, unlike the comparison groups, were not better at
      recalling their own placements. A second experiment tested the prediction arising
      from the monitoring-deficit account that the children with autism would be
      unimpaired when the placement of the items did not alternate between self and
      other. This prediction was confirmed moderately well. Additionally, in contrast
      to that of the comparison groups, the performance of the participants with autism
      was unaffected by whether self or other displaced the items. This is consistent
      with the existence of a monitoring deficit.

PMID- 16571512
TI  - Does long-term memory deficit relate to patients' slowness in schizophrenia?
AB  - INTRODUCTION: The performance of fast and slow schizophrenic patients and matched
      controls was examined in a delayed free recall task to assess whether the
      patient's slowness would influence long-term memory (LTM) in a similar way to
      working memory. METHOD: Twenty-three schizophrenic patients who met DSM-IV
      criteria and were matched in age and educational level to 23 controls
      participated. Subjects' reading rate was measured, and a cut-off of mean
      controls' reading rate minus 2 standard deviations was allowed the identification
      of 9 slow patients. The memory task comprised a list of 20 unrelated common words
      presented visually that were to be recalled in any order after a delay of 25-30
      minutes filled with unrelated tasks. RESULTS: The overall patients' performance
      was poor compared with controls, and slow and fast performance was comparable,
      contrasting with immediate memory tasks in which slow patients were impaired
      compared with fast patients. CONCLUSION: Patients' slowness does not seem to
      influence the long-term memory deficit in schizophrenia.

PMID- 16571514
TI  - Language processing and hallucinated "voices:" insights from transcranial
      magnetic stimulation.

PMID- 16571513
TI  - Face processing in schizophrenia: parallels with the effects of amygdala damage.

PMID- 16571516
TI  - Delusions as performance failures.
AB  - Delusions are explanations of anomalous experiences. A theory of delusion
      requires an explanation of both the anomalous experience and the apparently
      irrational explanation generated by the delusional subject. Hence, we require a
      model of rational belief formation against which the belief formation of
      delusional subjects can be evaluated. METHOD: I first describe such a model,
      distinguishing procedural from pragmatic rationality. Procedural rationality is
      the use of rules or procedures, deductive or inductive, that produce an
      inferentially coherent set of propositions. Pragmatic rationality is the use of
      procedural rationality in context. I then apply the distinction to the
      explanation of the Capgras and the Cotard delusions. I then argue that delusions
      are failures of pragmatic rationality. I examine the nature of these failures
      employing the distinction between performance and competence familiar from
      Chomskian linguistics. RESULTS: This approach to the irrationality of delusions
      reconciles accounts in which the explanation of the anomalous experience exhausts
      the explanation of delusion, accounts that appeal to further deficits within the
      reasoning processes of delusional subjects, and accounts that argue that
      delusions are not beliefs at all. (Respectively, one-stage, two-stage, and
      expressive accounts.) CONCLUSION: In paradigm cases that concern cognitive
      neuropsychiatry the irrationality of delusional subjects should be thought of as
      a performance deficit in pragmatic rationality.

PMID- 16571517
TI  - A test of central coherence theory: can adults with high-functioning autism or
      Asperger syndrome integrate fragments of an object?
AB  - INTRODUCTION: Visuoconceptual integration was explored as a test of central
      coherence theory (Frith, 1989). Individuals with autism are thought to have weak
      central coherence so the prediction was that these individuals would show an
      impaired ability to integrate visual information. METHOD: Two groups with
      autistic disorder were recruited: adults with either autism or Asperger syndrome.
      All were normally intelligent and were matched with members of the general
      population of Cambridge. A modified version of the Hooper Visual Organisation
      Test was used in which line drawings depicting simple objects had been cut into
      pieces and arranged in a puzzle-like fashion. The participants were required to
      conceptually integrate the fragments in order to identify the object. A second
      condition presented just a single piece of an object and participants were
      required to identify objects from a single piece. RESULTS: Both clinical groups
      were significantly impaired in their ability to integrate pieces holistically,
      but they were unimpaired in their ability to identify an object from a single
      piece. CONCLUSION: Individuals with an autistic disorder are less able to
      integrate visual elements. Of the two clinical groups, the autism group had the
      greater deficit, and it applied to the majority of the group. Possible
      explanations for the clinical groups' weak central coherence are explored.

PMID- 16571525
TI  - Implicit motion perception in schizotypy and schizophrenia: a Representational
      Momentum study.
AB  - INTRODUCTION: Human observers exhibit a distortion in recognition memory for
      pictures that imply motion because of an automatic mental process, which
      extrapolates along the implied trajectory of the picture. This is known as
      Representational Momentum (RM). Converging evidence (functional imaging; magnetic
      stimulation studies) suggests activity in area MT/MST (V5) is necessary for RM to
      occur. Patients with schizophrenia and healthy schizotypic individuals have been
      found to show motion perception deficits and abnormal eye-tracking (both
      indicative of abnormal functioning within brain area V5), therefore it was
      hypothesised that these individuals would show a reduced or absent RM effect.
      METHOD: Fifty healthy individuals and seven patients diagnosed with schizophrenia
      undertook a task previously found to elicit the RM effect. RESULTS: Although the
      size of the RM effect was not significantly different between either low and high
      schizotypes or low schizotypes and patients, there was a trend (in the opposite
      direction to that predicted) for the patients with schizophrenia and the high
      schizotypes to exhibit a larger RM effect. CONCLUSION: The findings are discussed
      in terms of functional connectivity between frontal areas and V5, and of
      schizophrenia involving a failure to inhibit automatic processes.

PMID- 16571526
TI  - Psychotic disorder following traumatic brain injury: a conceptual framework.
AB  - INTRODUCTION: Psychotic Disorder Following Traumatic Brain Injury (PDFTBI) is a
      relatively rare disorder that may provide clues to understanding schizophrenia
      and psychosis. The objective of this paper was to develop a conceptual framework
      describing how traumatic brain injury (TBI) can contribute to the development of
      a psychosis and potential neurobiological mechanisms that cause a psychosis in
      this population. METHODS: The literature on PDFTBI and previous
      conceptualisations of the disorder were reviewed. A model of psychosis was
      described as a context for a conceptualisation of PDFTBI. RESULTS: PDFTBI is
      associated with abnormalities to the temporal and frontal areas. The general
      presentation includes persecutory delusions and auditory hallucinations with an
      absence of negative symptoms. The mean onset is 4-5 years after TBI with the
      majority of cases occurring within 2 years. The progression and course of PDFTBI
      is variable. Neuroleptics appear to be the most efficacious medication. Previous
      conceptualisations of PDFTBI are varied and suggest that the relationship is not
      a simple one. CONCLUSION: We propose that psychosis results from damage to the
      frontal and temporal areas and dysregulation of the dopaminergic system. Everyone
      is vulnerable to a psychotic disorder and psychosis will result when a threshold
      of damage to these areas are attained. Traumatic brain injury can be the primary
      cause of psychosis or contribute to the development of a psychosis through
      secondary seizure disorder, increasing biological and psychological risk, and
      triggering psychosis in vulnerable patients. The relationship may also be
      coincidental. Traumatic brain injury triggers pathophysiological processes that
      generally result in a psychosis after a delay of 1-5 years. Directions for future
      research includes prospective studies examining the impact of TBI on developing
      psychosis, retrospective studies examining TBI as a risk factor in schizophrenia
      or other populations at risk for secondary psychosis, and studies examining
      prevention of psychotic illness.

PMID- 16571527
TI  - Dual-task performance in adults with autism.
AB  - INTRODUCTION: Based on previous evidence of executive function deficits in
      autism, it was hypothesised that people with autism would demonstrate a pattern
      of spared abilities on the slave system of working memory, although demonstrating
      an overt deficit of the central executive. METHOD: The performance of a group of
      adults with autism (n = 16) and that of a matched control group of healthy
      volunteers (n = 16) was compared over a range of executive tasks including dual
      task performance. RESULTS: The results are broadly consistent with the initial
      hypothesis: the performance on the dual task of the people with autism was
      impaired with respect to that of the control group. However, no differences
      emerged between the two groups in the performance of individual components of the
      task. CONCLUSION: All executive tests used in this study predicted the inclusion
      in the autistic group but there was not a high correlation among executive
      scores.

PMID- 16571529
TI  - Cognitive functioning and social problem-solving skills in schizophrenia.
AB  - INTRODUCTION: This study examined the relationships between symptoms, cognitive
      functioning, and social skill deficits in schizophrenia. Few studies have
      incorporated measures of cognitive functioning and symptoms in predictive models
      for social problem solving. METHOD: For our study, 44 participants were recruited
      from consecutive outpatient admissions. Neuropsychological tests were given to
      assess cognitive function, and social problem solving was assessed using
      structured vignettes designed to evoke the participant's ability to generate,
      evaluate, and apply solutions to social problems. A sequential model-fitting
      method of analysis was used to incorporate social problem solving, symptom
      presentation, and cognitive impairment into linear regression models. Predictor
      variables were drawn from demographic, cognitive, and symptom domains. Because
      this method of analysis was exploratory and not intended as hierarchical
      modelling, no a priori hypotheses were proposed. RESULTS: Participants with
      higher scores on tests of cognitive flexibility were better able to generate
      accurate, appropriate, and relevant responses to the social problem-solving
      vignettes. CONCLUSIONS: The results suggest that cognitive flexibility is a
      potentially important mediating factor in social problem-solving competence.
      While other factors are related to social problem-solving skill, this study
      supports the importance of cognition and understanding how it relates to the
      complex and multifaceted nature of social functioning.

PMID- 16571530
TI  - Interhemispheric transfer and laterality effects in simple visual reaction time
      in schizophrenics.
AB  - INTRODUCTION: There is evidence that schizophrenics have an abnormal corpus
      callosum and an abnormal pattern of cerebral asymmetries. We investigated whether
      there are corresponding functional abnormalities in interhemispheric transfer
      (IT) and laterality effects. METHODS: Medicated schizophrenic patients and
      matched controls were tested in the Poffenberger paradigm, that is, a simple
      manual reaction time (RT) paradigm with laterally presented visual stimuli
      designed to provide a behavioural estimate of IT. By subtracting RT averaged
      across the uncrossed hand-hemifield conditions, from RT averaged across the
      crossed hand-hemifield conditions, one can obtain an estimate of IT time.
      RESULTS: In schizophrenic patients the difference between crossed and uncrossed
      conditions was 0 because of an unusually prolonged RT in the uncrossed condition
      right hand/ right field. A broadly similar result has been obtained previously in
      the tactile modality (Ditchfield & Hemsley, 1990) and is consistent with a left
      hemisphere impairment. This effect was still present when the patients were
      retested about 2 years later. CONCLUSIONS: These results demonstrate the
      existence in schizophrenic patients of a consistent slowing down of simple
      visuomotor responses subserved by the left hemisphere.

PMID- 16571531
TI  - The role of affect and reasoning in a patient with a delusion of
      misidentification.
AB  - INTRODUCTION: This study investigated a patient with a delusion of
      misidentification (DM) resembling a Capgras delusion. Instead of the typical
      Capgras delusion--the false belief that someone has been replaced by an almost
      identical impostor--patient MF misidentified his wife as his former business
      partner. METHOD: Detailed investigation of MF's face processing, affective
      response and affect perception, and ability to evaluate, and reject, implausible
      ideas was undertaken. RESULTS: MF's visual processing of identity, gender, and
      age of familiar and unknown faces was intact but he was unable to identify the
      facial expressions of anger, disgust, and fear, or to match faces across
      expressions. MF also showed a reduced affective responsiveness to his
      environment, and impaired reasoning ability. CONCLUSIONS: We propose that MF's
      delusion of misidentification resulted from a combination of affective deficits,
      including impairment of both affective response and affect perception, in
      addition to an inability to evaluate, and reject, implausible ideas. These
      deficits, in combination with specific life events at the time of onset of the
      delusion, may have contributed to the form and content of the delusion. In
      addition, the results raise the possibility that the processing of face identity
      and facial expression are not as independent as previously proposed in models of
      face processing.

PMID- 16571532
TI  - Perception of self-generated action in schizophrenia.
AB  - INTRODUCTION: Self-generated actions involve central processes of sensorimotor
      integration that continuously monitor sensory inputs to ensure that motor outputs
      are congruent with our intentions. This mechanism works automatically in normal
      conditions but becomes conscious whenever a mismatch happens during the execution
      of action between expected and current sensorimotor reafferences. It is now
      admitted in the literature that sensorimotor processes as well as the ability to
      predict the consequences of our own actions imply the existence of a forward
      model of action, which is based on efference copies. Recently, it has been
      proposed that positive symptoms expressed by schizophrenic patients, such as
      delusions of control or thought insertions, arise because of a deficiency in this
      forward model, and more particularly, because of a lack of awareness of certain
      aspects of motor control derived from such an internal model. METHOD: To test
      further this hypothesis, 19 schizophrenic patients (10 with and 9 without
      Schneiderian symptoms) and 19 control subjects performed a visuo-motor conflict
      task and had verbally to report the felt position of their hand at the end of
      each trial. RESULTS: Under this experimental procedure, schizophrenic patients-
      whatever their clinical phenotype--failed to switch to a conscious representation
      of their hand movements, and then consequently to maintain their level of
      performance for the sensorimotor adjustment in comparison with controls.
      CONCLUSION: Our findings suggest two facts. First, that a functional monitoring
      of action, based on a forward.

PMID- 16571534
TI  - Pathologies of body, self, and space.

PMID- 16571535
TI  - Alien abduction experiences: Some clues from neuropsychology and neuropsychiatry.
AB  - INTRODUCTION: Many thousands of people around the world firmly believe that they
      have been abducted by alien beings and taken on board spaceships where they have
      been subjected to painful medical examination. METHOD: Given that such accounts
      are almost certainly untrue, four areas of neuroscience are considered with
      respect to possible clues that may lead towards a fuller understanding of the
      alien abduction experience. RESULTS: First, it is argued that sleep paralysis may
      be implicated in many such claims. Second, research into false memories is
      considered. It is argued that abductees may be more prone to false memories than
      the general population. Third, evidence is considered relating to the mental
      health of abductees. It is concluded that there is currently no convincing
      evidence for higher rates of serious psychopathology amongst abductees compared
      to the general population. However, abductees do seem to show higher levels on
      some potentially relevant measures (e.g., tendency to dissociate). Finally,
      claims that alien abduction experiences may be linked to abnormal activity in the
      temporal lobes is considered. CONCLUSION: Although the neurosciences provide many
      clues to the nature of this bizarre experience, further research is required
      before a full understanding will be attained.

PMID- 16571536
TI  - Reflective mirrors: perspective-taking in autoscopic phenomena.
AB  - INTRODUCTION: ''Autoscopic phenomena refer to different illusory reduplications
      of one's own body and self. This article proposes a phenomenological
      differentiation of autoscopic reduplication into three distinct classes, i.e.,
      autoscopic hallucinations, heautoscopy, and out-of-body experiences (OBEs).
      METHOD: Published cases are analysed with special emphasis on the subject's point
      of view from which the reduplication is observed. RESULTS: In an autoscopic
      hallucination the observer's perspective is clearly body-centred, and the visual
      image of one's own body appears as a mirror reversal. Heautoscopy (i.e., the
      encounter with an alter ego or doppelganger), is defined as a reduplication not
      only of bodily appearance, but also of aspects of one's psychological self. The
      observer's perspective may alternate between egocentric and ''alter-ego
      centred''. As a consequence of the projection of bodily feelings into the
      doppelganger (implying a mental rotation of one's own body along the vertical
      axis), original and reduplicated bodies are not mirror images of one another.
      This also holds for OBEs, where one's self is not reduplicated but appears to be
      completely dissociated from the body and observing it from a location in
      extracorporeal space. It is argued that perspective-taking in a spatial sense may
      be meaningfully related to perspective-taking in a psychological sense. The
      mirror in the autoscopic hallucination is a ''cognitively nonreflective mirror''
      (Jean Cocteau), both spatially and psychologically. The reflective abilities of
      the heautoscopic mirror are better developed, yet frequent shifts in the
      observer's spatial perspective render the nature of psychological interactions
      between self and alter ego highly unpredictable. The doppelganger may serve a
      transitivistic (i.e., own suffering is transferred to the alter ego) or
      aggressive function when this behaviour is directed against a patient. The mirror
      in an OBE is always reflective: It allows the self to view both space and one's
      psychological state from a detached but stable perspective. CONCLUSIONS: Spatial
      perspective-taking should be more thoroughly assessed in patients reporting
      autoscopic phenomena. By elucidating the interactions between spatial
      phenomenology and psychological function, we may gain important insights into the
      relationships between the self, its body, and phenomenal space.

PMID- 16571537
TI  - Cognitive neuroscience of hemispatial neglect.
AB  - INTRODUCTION: Patients with neglect often fail to be aware of stimuli located on
      their contralesional side--the side of space opposite their brain damage. Some
      patients show impairments in extrapersonal space; others within personal (body)
      space; and some in both. Although the neglect syndrome may be associated with a
      distorted perception of extrapersonal or personal space, recent investigations
      suggest that attentional, memory and motor deficits may be important additional
      components. CONCLUSION: Better understanding of these cognitive impairments holds
      the key to offering effective treatment for neglect, as well as providing
      important insights into normal brain function.

PMID- 16571538
TI  - Alien motor phenomena: a window on to agency.
AB  - INTRODUCTION: Alien motor phenomena arise in neurological and psychiatric
      contexts and are likely to implicate several distributed brain systems. METHOD: A
      selective literature review, focusing on cognitive neurobiological accounts of
      alien/anarchic limb, somatoparaphrenia, and delusions of alien control (passivity
      phenomena); supplemented by an account of the cognitive neuroanatomy of action
      and agency (subjective sense of causation) in the normal state. RESULTS: Alien
      motor phenomena reflect impairments of agency through at least two mechanisms.
      (1) A disinhibition of ''lower'' motor centres giving rise to relatively
      stereotypic and contextually inappropriate motor routines (as emerge following
      medial frontal and corpus callosal lesions). (2) A disturbance of the perception
      of self-initiated movement, so that control of movement (causation) is attributed
      to an alien entity (phenomena associated with right parietal lobe lesions, focal
      epilepsy, and hyperactivity in acute schizophrenia). CONCLUSION: Whereas
      alien/anarchic limb dysfunction may be relatively easily explained in cognitive
      neurobiological terms, a comprehensive account of alien control will require
      further empirical ingenuity. Current models invoke disturbed feed-forward
      mechanisms, imitation, and the sense of another's agency (''nonself
      attribution'').

PMID- 16571539
TI  - The cognitive psychology of dissociative states.
AB  - INTRODUCTION: A number of theoretical models have identified dissociation as a
      possible cognitive mechanism underlying medically unexplained symptoms
      (''hysteria''). A review of research and theory in this area indicates that the
      dissociation concept is a useful explanation of this phenomenon. However,
      existing models of dissociation have a number of explanatory shortcomings.
      METHODS: This article describes a recent model of unexplained illness that aims
      to extend the dissociation concept by reference to research and theory from
      contemporary cognitive psychology. RESULTS: According to this view, unexplained
      symptoms should be regarded as disturbances of consciousness and behavioural
      control, resulting from the chronic activation of stored symptom representations
      within memory. This process is driven by the repeated reallocation of high-level
      attention on to symptom representations. CONCLUSIONS: The model offers a fresh
      perspective on the nature of unexplained symptoms, providing an explicit account
      of the factors involved in the creation and maintenance of this phenomenon.

PMID- 16571540
TI  - Thought insertion, cognitivism, and inner space.
AB  - INTRODUCTION: Whatever its underlying causes, even the description of the
      phenomenon of thought insertion, of the content of the delusion, presents
      difficulty. It may seem that the best hope of a description comes from a broadly
      cognitivist approach to the mind which construes content-laden mental states as
      internal mental representations within what is literally an inner space: the
      space of the brain or nervous system. Such an approach objectifies thoughts in a
      way which might seem to hold out the prospect of describing the ''alienated''
      relation to one's own thoughts that seems to be present in thought insertion.1
      METHOD: Firstly, I examine the general structure of cognitivist accounts of
      intentional or content-laden mental states. I raise the general difficulty of
      explaining how free-standing, and thus world-independent, inner states can still
      have bearing on the outer world. Secondly, I briefly examine Frith's model for
      explaining thought insertion and other passivity phenomena by postulating a
      failure of an internal monitoring mechanism of inner states. I question what
      account can be given of non-pathological cases and raise two specific objects.
      RESULTS: Cognitivist accounts of the mind face a general, and possibly
      insuperable, challenge: explaining the intentionality of mental states in non
      intentional, nonquestion-begging terms. There have so far been no satisfactory
      solutions. Cognitivist accounts of passivity phenomena in terms of a failure of
      internal monitoring face two objections. Firstly, accounting for non-pathological
      cases generates an infinite regress. Secondly, no account can be given of the
      paradoxical nature of utterances of the form of Moore's paradox: ''it is raining
      but I do not believe it''. CONCLUSIONS: A cognitivist approach presents an
      alienated account of thought in normal, non-pathological cases and is no help in
      accounting for thought insertion.

PMID- 16571541
TI  - Phantom limbs: The body in mind.
AB  - INTRODUCTION: Advances in our knowledge of corporeal awareness is not limited to
      patients with amputations, however, until recently, the study of ''phantom
      limbs'' was neglected by comparison with less common disorders of body
      perception. METHOD: Reasons for the neglect of this potentially informative and
      common condition are conspicuous by their absence in previous reviews. Over the
      past decade, however, experimental investigations of phantom limbs have revealed
      the dynamic neural processes that provide for both phantom and normal corporeal
      embodiment. Moreover, these findings helped to overturn widely held scientific
      assumptions regarding the extent of neural plasticity in the adult brain.
      RESULTS: It is suggested that throughout medical history, the construct of
      ''phantom limbs'' posed a challenge to fundamental folk assumptions regarding the
      assumed relationship between body and mind. CONCLUSION: Reluctance to entertain
      the counter-intuitive phenomenon of a ''limbless perception'' contributed to the
      comparative neglect of this fascinating phenomenon until the late 20th century.

PMID- 16571542
TI  - Deficits in auditory and visual temporal perception in schizophrenia.
AB  - INTRODUCTION: Characteristics of time perception have not been well documented in
      patients with schizophrenia. The current study investigated time estimation to
      (1) test whether visual and auditory time perception varied between patients and
      controls, (2) assess the degree to which patients and controls can differentiate
      changes in experimental intervals, and (3) explore whether the temporal deficits
      suggest a general time perception deficit versus modality-specific differences.
      METHODS: Participants were asked to decide whether temporal intervals were
      shorter or longer than standard intervals on computer-based auditory and visual
      temporal perception tasks. Data are presented for a sample of 10 patients with
      schizophrenia and 10 normal controls. RESULTS: Data suggest that patients with
      schizophrenia exhibit deficits in differentiating subtle differences in intervals
      in the tens of milliseconds range, compared to their normal control peers on both
      auditory (p < .01) and visual perception tasks (p < .01). CONCLUSIONS:
      Preliminary data suggest that there is a general temporal processing deficit in
      schizophrenia. However, future research using complementary techniques may
      provide useful information regarding the specific types of temporal deficits that
      affect patients with schizophrenia and the physiology of the dysfunction.

PMID- 16571543
TI  - Time course of inhibition and facilitation in patients with schizophrenia.
AB  - INTRODUCTION: Negative priming (NP) paradigms have been used extensively to
      understand the nature and time course of inhibitory deficits in patient
      populations. A majority of these studies have reported abnormal NP effects, with
      patients showing faster reaction times on NP sequences compared to the slowing
      displayed by controls. METHODS: A Stroop NP task was employed to measure
      immediate (within-trial) attentional processing as well as the sustainment
      (between-trial) of these processes in 12 medicated schizophrenia inpatients and
      13 matched controls. Two response stimulus intervals (RSIs) were presented (500
      ms and 2000 ms). Within-trial Stroop effects (interference and facilitation) and
      between-trial priming effects (negative and positive priming) were measured.
      Clinical symptomatology and duration of illness were also examined. RESULTS: At
      short RSIs of 500 ms, chronically ill state hospital schizophrenia patients
      failed to exhibit NP. In contrast, the control subjects exhibited normal NP at
      the short RSI but this priming faded at the long 2000 ms RSI and was no longer
      significant. The facilitatory priming effects remained stable across time in both
      groups. CONCLUSIONS: These results suggest that schizophrenia patients are better
      able to inhibit irrelevant stimuli that are immediate, but the sustainment of
      inhibition across very short time intervals (500 ms) may fade compared to
      controls.

PMID- 16571544
TI  - An examination of the suppression of overlearned responses in schizophrenia.
AB  - INTRODUCTION: Individuals often experience interference from overlearned
      responses. This phenomenon is reported to be increased in patients with
      schizophrenia. METHODS: In order to determine the generality of such interference
      in these patients, the frequency of repetitive responses in simple tasks was
      manipulated. It was hypothesised that patients' performance would be
      disproportionately impaired when a strong response tendency needed to be
      overridden. This was expected to be the case especially where task rules had to
      be maintained for a period of time in order to respond appropriately. RESULTS: A
      spatial analogue of the Stroop test, with a response bias to a side of space,
      produced stronger expectancy in patients than in controls. A similar manipulation
      of expectancy in a variant of the Continuous Performance Test, in which subjects
      were to respond to sequentially presented pairs of letters, did not result in a
      difference between patients and controls in terms of inhibiting inappropriate
      responses. In this test, patients' deficits were associated with the delay period
      between stimulus and target. CONCLUSIONS: The cognitive impairment in patients
      with schizophrenia is not simply a general deficit in the suppression of
      overlearned responses, rather, the susceptibility to interference appears more
      task specific.

PMID- 16571545
TI  - The emergence of delusional companions in Alzheimer's disease: an unusual
      misidentification syndrome.
AB  - INTRODUCTION: Misidentifications in the course of organic diseases, including
      Alzheimer's disease (AD), have been associated with right sided brain
      dysfunction. The reasons for this association might be clarified by investigating
      the contribution of neurobiological, cognitive and emotional factors to
      distinctive types of misidentification. METHODS: This study reports the cases of
      three patients with AD presenting a novel misidentification delusion in which
      objects with intrinsically comforting associations, soft toys, were experienced
      as sentient and triggered associated behaviours. Investigations included regional
      cerebral blood flow (rCBF) measurements with HMPAO SPECT and a comprehensive
      clinical and neuropsychological assessment. RESULTS: All three patients showed a
      distinctive pattern of rCBF with dysfunction centred in the right parietal area
      and severe visuospatial and visuoperceptive processing deficits, with relatively
      preserved memory and language abilities. CONCLUSION: These findings support the
      hypothesis that this type of misidentification delusion may be facilitated by
      right sided regional brain dysfunction involving visuoperceptual processing.
      Other historical and cognitive data from these patients suggests that the
      appearance of the symptom may be determined by the coexistence of a more
      widespread disorder of reality processing, which interacts with cognitive and
      psychogenic factors.

PMID- 16571547
TI  - Neurorehabilitation for two cases of post-traumatic stress disorder following
      traumatic brain injury.
AB  - INTRODUCTION: We present two cases to illustrate the assessment and management of
      post-traumatic stress disorder (PtSD) in the context of traumatic brain injury
      (TBI). Case KE suffered a TBI in a road traffic accident (RTA) in which his
      girlfriend was killed. Case CM survived a penetrating neurological injury from a
      severe knife attack. Both suffered cognitive difficulties, primarily in attention
      and memory, and selective visual impairments, and had endured significant losses
      of social role. METHOD: Within a neurorehabilitation programme, goals were set
      regarding management of their cognitive difficulties for regaining social roles
      and for the management of their PtSD symptoms. Cognitive behavioural therapy
      (CBT) was provided for managing PtSD symptoms, which included use of a stress
      inoculation and graduated exposure to avoided situations and trauma re
      experiences. RESULTS: Both survivors reported significant improvements in
      managing mood state, and in redeveloping social roles. Objective measures
      confirmed significant gains from intervention. CONCLUSIONS: CBT, set within a
      neurorehabilitation programme, can lead to improvement in PtSD symptoms and
      psychosocial outcome in TBI survivors.

PMID- 16571548
TI  - Visual scanpaths and facial affect recognition in delusion-prone individuals:
      Increased sensitivity to threat?
AB  - INTRODUCTION: Using visual scanpaths as a measure of directed attention, we
      investigated whether delusion-prone individuals would exhibit reduced visual
      appraisal, and impaired recognition accuracy, for threat-related facial
      expressions. METHODS: 47 psychiatrically healthy individuals completed the Peters
      et al. Delusions Inventory (PDI) as an index of delusion-proneness; experimental
      groups of high and low PDI scorers were formed on the basis of a median split.
      Visual scanpaths were recorded while participants viewed photographs of faces
      displaying anger, fear, happy, sad, and neutral expressions under a free-viewing
      condition. Affect recognition accuracy was assessed using a forced-choice
      response format. RESULTS: The high PDI group displayed generally "extended"
      scanpaths, characterised by increased distances between fixations, for angry,
      fearful, and happy faces, but exhibited a distinctive pattern of reduced foveal
      attention (fewer fixations) for facial expressions of anger and fear. Impaired
      affect recognition accuracy in the high PDI group was most pronounced for fearful
      faces. Reduced recognition accuracy for fearful faces was associated with longer
      distances between fixations in the entire group. CONCLUSIONS: Delusion-prone
      individuals displayed a bias of directing attention away from threat-related
      faces, and a trend toward reduced recognition accuracy for fearful faces,
      suggesting that these individuals may be particularly sensitive to facial threat.

PMID- 16571549
TI  - A case of paraprosopia and its treatment.
AB  - INTRODUCTION: The present case study describes the neuropsychological testing and
      a cognitive-behavioural treatment for a 45-year-old female with paraprosopia--the
      experience of seeing faces sometimes distorted in grotesque and threatening ways.
      METHOD: The treatment focused on relaxation training, exposure, and cognitive
      restructuring. Ratings of subjective distress, self-reports and mood rating scale
      data were collected throughout an 8-week treatment period. Follow-up was at 6
      weeks and 6 months. RESULTS AND CONCLUSIONS: Both subjective ratings and clinical
      interview suggested a reduction in the frequency of seeing the face and a
      substantial reduction in associated distress. Evidence for generalisation was
      less compelling. Suggestions are made for future psychological treatment of this
      uncommon disorder.

PMID- 16571550
TI  - "Gamma (40 Hz) phase synchronicity" and symptom dimensions in schizophrenia.
AB  - INTRODUCTION: The failure of integrative brain function is a fundamental
      characteristic of schizophrenia. Synchronous Gamma (40 Hz) activity, proposed as
      a candidate mechanism underlying the integration ("binding") of distributed brain
      activities, may provide a direct window into schizophrenic disintegration.
      METHODS: 40 schizophrenia and 40 age/gender-matched control subjects participated
      in an auditory oddball paradigm. We examined both early (Gamma 1) and later Gamma
      (Gamma 2) phase synchrony to target stimuli. Factor analysis scores were used to
      examine the associations between Gamma synchrony and three syndromes (Psychomotor
      Poverty, Reality Distortion, and Disorganisation). RESULTS: Multiple analyses of
      variance revealed an overall decrease in frontal and left hemisphere Gamma
      synchrony, but increased posterior Gamma 2 synchrony in schizophrenia compared to
      controls. Schizophrenia syndromes were differentiated by distinct patterns of
      Gamma disturbances: Psychomotor Poverty showed decreased left hemisphere
      synchrony; Reality Distortion was associated with increased right synchrony;
      Disorganisation showed a widespread enhancement with a delay in frontal Gamma
      synchrony. CONCLUSIONS: These findings are consistent with previous evidence for
      left hemisphere and frontal disturbances in the schizophrenia group. However, the
      syndrome results point to more distinctive patterns of dysregulation in network
      integration: widespread and excessive in Disorganisation, localised and enhanced
      in Reality Distortion, versus localised and diminished in Psychomotor Poverty.

PMID- 16571552
TI  - Neuroanatomical correlates of formal thought disorder in schizophrenia.
AB  - INTRODUCTION: We attempted to extend findings of a relationship between formal
      thought disorder and left superior temporal gyrus (STG) volume in schizophrenia
      by examining two indices of formal thought disorder. METHODS: Three brain regions
      of interest were selected from magnetic resonance imaging slices in 15 young,
      right-handed, male schizophrenia patients: the STG, the anterior hippocampus, and
      the amygdala. Thought disorder was assessed using the Bizarre-Idiosyncratic
      Thinking (BIZ) scale, a sensitive measure of formal thought disorder based on
      responses to a standard set of stimuli, and the BPRS Conceptual Disorganization
      item, a global rating based on a clinical interview. RESULTS: BIZ ratings of
      thought disorder were significantly correlated with the left STG volume (Spearman
      r = -.73) and with the right STG volume (Spearman r = -.58). BIZ ratings were not
      significantly correlated with either the left or right anterior hippocampus or
      amygdala volumes. The BPRS Conceptual Disorganisation rating was not
      significantly related to the STG, anterior hippocampus, or amygdala volumes.
      CONCLUSIONS: This study confirms the previously reported association between the
      left STG and formal thought disorder, and suggests that detection of this
      relationship may be facilitated by use of highly sensitive formal thought
      disorder assessments.

PMID- 16571553
TI  - Auditory temporal processing in schizophrenia: high level rather than low level
      deficits?
AB  - INTRODUCTION: Patients with schizophrenia demonstrate a wide range of information
      processing deficits. Most recent studies argue in favour of high level deficits,
      including attention and context processing, whereas fewer studies have
      demonstrated deficits at earlier stages of processing, such as perceptual
      discrimination and organisation. This is the first study to investigate both high
      and low level processing, within a single paradigm, in the case of auditory
      temporal processing in schizophrenia. METHODS: Patients with schizophrenia were
      compared to controls on a series of tasks involving three auditory temporal
      processes varying from low to higher level: (1) segregation of a complex sequence
      into component auditory streams; (2) detection of local temporal irregularities
      within a stream; (3) attentional focusing on one stream by the use of a cue
      preceding the complex sequence. RESULTS: The lowest level of processing examined
      here--stream segregation--appeared to function equally well in patients as in
      controls. However, the higher level processes--irregularity detection and
      attentional focus--functioned in both groups, but less efficiently in patients
      with schizophrenia. CONCLUSIONS: Results demonstrate abnormal auditory temporal
      processing in schizophrenia. Abnormal performances only in Processes 2 and 3
      support and hypothesis of higher level rather than lower level processing
      deficits in schizophrenia.

PMID- 16571554
TI  - Slowed lexical access is uniquely associated with positive and disorganised
      symptoms in schizophrenia.
AB  - INTRODUCTION: This study addressed the relationship of both semantic priming and
      slowed lexical access to the symptoms of schizophrenia, and evaluated their
      association with other neurocognitive deficits. METHODS: 57 outpatients with
      schizophrenia and 20 nonpsychiatric control subjects performed a lexical decision
      semantic priming task (LDT), and a brief neuropsychological battery. The
      schizophrenia group was also assessed with an extended Positive and Negative
      Symptom Scale. RESULTS: As expected, the schizophrenia group had significantly
      slower reaction times (RTs) than the control group, and poorer performance on
      most neuropsychological tasks. Both groups exhibited semantic priming effects in
      both automatic and controlled processing conditions; these effects were not
      significantly different between groups. RT was unrelated to age, illness
      duration, GAF scores, or neuroleptic dose; controlled semantic priming effects
      were related to illness duration only. RT to real word targets (but not to
      nonwords) on the LDT was significantly correlated with positive and disorganised,
      but not negative symptoms. The neurocognitive correlates of RT slowing were: full
      scale IQ and verbal fluency, but not attention; working memory; episodic memory
      retrieval; executive function, or manual speed. Both controlled semantic priming
      effects as well as the difference between controlled and automatic priming
      effects were related to executive functions in general. Severity of symptoms in
      the three major symptom groups was generally unassociated with impairment on the
      neuropsychological battery. The associations of RT slowing to positive and
      disorganised symptoms remained even after controlling for each of the above
      clinical and neurocognitive measures. CONCLUSIONS: These findings suggest that in
      schizophrenia, slowed lexical access is uniquely related to positive and
      disorganised symptoms. This relationship is not accounted for by more general
      cognitive deficits, overall illness severity, or generalised effects of symptoms
      on cognitive function. This relationship may reflect a specific impairment in the
      access to semantic memory.

PMID- 16571555
TI  - Reasoning about physical causality and other's intentions in schizophrenia.
AB  - INTRODUCTION: Several studies have shown that schizophrenic patients have
      impaired theory-of-mind skills involving the attribution of false beliefs and
      intentions to others. Despite the methodological difficulties of false belief
      protocols, experiments have concluded that the deficit is specific and cannot be
      explained in terms of a general cognitive impairment. The situation, however,
      remains unclear as far as the attribution of intentions to others is concerned.
      We propose the use of nonverbal control tasks based on physical causality to
      demonstrate the specificity of the impairment of attribution of intentions.
      METHODS: We compared the performances of schizophrenic patients and normal
      subjects on the attribution of intentions and on two control tasks involving
      physical causality (reasoning about the weight, location, speed, and the physical
      properties of objects). 25 schizophrenic patients and 25 healthy subjects
      participated in the study. Each subject was assessed under three conditions using
      comic strips: attribution of intentions, physical causality with characters,
      physical causality without characters. RESULTS: The performances of schizophrenic
      patients differed significantly from those of healthy subjects only in the
      attribution of intentions condition. This difference was also found when only
      subjects having optimal performances in physical logic were considered and when
      verbal IQ was considered as a co-variable. CONCLUSIONS: Nonverbal attribution of
      intentions to others is specifically impaired in schizophrenia. This conclusion
      is in agreement with recent neuroimaging findings.

PMID- 16571556
TI  - Prospective memory impairment in abstinent MDMA ("Ecstasy") users.

PMID- 16571558
TI  - The relationship between depressive symptoms and cognitive dysfunction in
      multiple sclerosis.
AB  - INTRODUCTION: Although it has been well established that otherwise healthy
      persons with depression experience various neuropsychological deficits, such a
      relationship has not been robustly supported in the initial investigations using
      the multiple sclerosis (MS) population. The relative inability to discover a
      significant relationship between depression and cognitive dysfunction may be due
      to methodological difficulties in previous studies (e.g., use of correlational
      analysis; use of neuropsychological measures that are generally not affected by
      depression). METHODS: The present study examined a control group and 17 MS
      subjects who reported relatively low (BDI h 9) or high (BDI S 16) depression
      levels on a variety of neurocognitive measures that were (i.e., PASAT, Digit Span
      Backward subtest of the WAIS-R, and a modified version of the Buschke Selective
      Reminding Test; SRT) or were not (i.e., Similarities, Vocabulary, and Digit Span
      Forward subtests of the WAIS-R) hypothesised to be associated with depression
      symptomatology. RESULTS: These results support our hypotheses that depressed
      individuals with MS evidence greater neuropsychological dysfunction relative to
      their nondepressed counterparts. CONCLUSION: Findings are discussed in terms of
      the specific cognitive impairments evidenced by depressed subjects with MS. This
      research may have significant implications with regard to the expected effects of
      antidepressant and cognitive therapies on neuropsychological functioning in MS.

PMID- 16571559
TI  - Semantic context-processing deficit in thought-disordered schizophrenic patients:
      evidence from new semantic priming paradigms.
AB  - INTRODUCTION: Disorders in the processing of the semantic context are now a well
      established phenomenon in thought-disordered (TD) schizophrenic patients, and
      have been revealed especially well by studies that have made use of the
      experimental paradigm of lexical decision tasks coupled with semantic priming.
      The main question addressed by this study was the evaluation of the experimental
      conditions under which TD schizophrenic patients are able to deploy cognitive
      strategies for semantic context processing. METHODS: We studied semantic priming
      in two double lexical decision tasks (i.e., involving the explicit processing of
      the prime word) using a sequential presentation of words (stimulus onset
      asynchrony; SOA 500 ms) with a different proportion of related words (Experiment
      1 with 25% vs. Experiment 2 with 15%) in 15 TD schizophrenic and 15 normal
      participants. RESULTS: The results showed no significant differences between the
      semantic priming of TD schizophrenic and normal participants for Experiment 1,
      unlike Experiment 2 in which we observed a significant reduction of the amplitude
      of semantic priming in TD schizophrenic patients. The results of Experiment 1
      contrast with those obtained previously (Besche et al., 1997) using a classical
      lexical decision task (implicit processing of the prime word) which also
      contained 25% related words. CONCLUSIONS: Experimental variables, such as the
      cognitive processing required by the prime word or the proportion of related
      words or the way they are manipulated, all seem to influence the emergence of
      semantic priming abnormalities in TD schizophrenic patients.

PMID- 16571560
TI  - Is theory-of-mind impaired in Parkinson's disease?
AB  - INTRODUCTION: Theory-of-mind (ToM) refers to the ability to understand and
      predict the behaviour of others based on their mental states. Research from brain
      imaging and lesion studies indicate that the frontal lobes are both involved and
      necessary to understand mental states. METHODS: A total of 13 people with
      Parkinson's disease were compared with 11 age-matched controls on tasks involving
      ToM, based on the hypothesis that the frontal lobes are affected by Parkinson's
      disease. The four tasks included both ToM and non-ToM components, such as memory,
      to investigate the specific nature of the deficit. RESULTS: The group with
      Parkinson's disease scored significantly lower on three out of four of the ToM
      components of the tasks, relative to controls, but were not impaired on any of
      the non-ToM components of the four tasks. CONCLUSION: The results suggest the
      impairment was specific to ToM and thus have implications for a dedicated
      specific ToM module.

PMID- 16571561
TI  - Dog phobia in a motion-blind patient.
AB  - INTRODUCTION: A prominent neurophysiological model of phobia generation holds
      that specific phobia might result from the uncoupling of unaware subcortical fear
      responses from aware cortical fear responses. Former responses are thought to be
      automatic and fast, providing approximate information about the external
      stimulus, whereas the latter responses are more controlled and allow comparison
      with previous experience. Since only the cortical pathway carries information
      available to awareness, this model also accounts for the striking irrationality
      of specific phobia in humans. METHODS: Here, we report neuropsychological and
      neuro-ophthalmological findings in a 41-year-old patient who developed severe dog
      phobia following bilateral parietal lobe damage. RESULTS: The examinations showed
      a severe deficit in visual motion perception (visual motion blindness or
      akinetopsia) as well as spatial vision. Importantly, the patient was largely
      unaware of his visual deficits. CONCLUSION: Based on the present observation it
      is argued that irrational fear, as found in specific phobia, might not only
      result from a general uncoupling of aware cortical from unaware subcortical fear
      responses, but also from a functionally similar dissociation at the cortical
      level.

PMID- 16571562
TI  - Inductive reasoning and the understanding of intention in schizophrenia.
AB  - BACKGROUND: The study explored the relationship between the understanding of
      intention in veiled speech acts and the ability to reason inductively. METHODS: A
      total of 39 people with DSM-IV-defined schizophrenia with no behavioural signs
      and 44 healthy participants performed the Hinting Task, a measure of pragmatic
      language in which the speaker's intention must be inferred, and a measure of
      inductive reasoning (Aha! Sentences) in which the meaning of ambiguous nonsocial
      sentences had to be inferred. The participants also completed measures of general
      intellectual ability, immediate memory for narrative and social problem-solving
      ability. RESULTS: A substantial correlation was found between performance on the
      inductive reasoning task and the Hinting Task in the sample of people with
      schizophrenia. The same relationship was not seen in the normal control sample.
      The robust relationship between these two measures in this sample survived when
      the roles of immediate memory for narrative and intellectual ability were
      controlled for. Furthermore, the relationship was distinctly more compelling for
      the patients who were currently ill compared to those in remission. CONCLUSION:
      These data suggest that people with schizophrenia use a different strategy to
      infer the meaning behind pragmatic language than that used by normally
      functioning adults. It is suggested that a reliance on different, possibly less
      specialised, skills in this group to perform this simple social inference task
      underlies their deficient performance on this and other measures of social
      inference. The fact that the relationship between the tasks in patients in
      remission is not as robust implies that the use of specialised skills to perform
      social inference tasks may be compromised most significantly during acute phases.

PMID- 16571564
TI  - Pragmatic language interpretation after closed head injury: relationship to
      executive functioning.
AB  - INTRODUCTION: Closed head injury is associated with impairment in a range of
      executive skills, and with everyday difficulties in social interactions.
      Comprehension of pragmatic language plays an important role in social
      interactions. The present study was designed to examine performance on a task
      involving pragmatic judgement in people who had suffered closed head injury
      (CHI), and the relationship between this and any impairments in executive skills.
      METHODS: Participants with CHI were compared to a matched healthy control group
      on a pragmatic inference task consisting of a series of brief vignettes.
      Participants made judgements about alternative responses in relation to social
      appropriateness/skill, and carried out several nonsocial executive tasks thought
      to play a role in pragmatic judgement. RESULTS: The CHI group was poorer than the
      control group on the pragmatic measure, showing less discrimination than the
      control group between direct, literal interpretations and correct, indirect
      interpretations. They also performed more poorly on the nonsocial executive
      measures. Regression analysis showed an association between pragmatic performance
      and one of the executive tasks, a measure of inhibition. CONCLUSIONS: More work
      is needed to explore further the nature of any relationship between pragmatic
      judgement and executive skills.

PMID- 16571565
TI  - Impact of comorbid depressive symptoms on nonverbal memory and visuospatial
      performance in obsessive-compulsive disorder.
AB  - INTRODUCTION: Recent research has suggested that some executive dysfunctions in
      obsessive-compulsive disorder (OCD) represent an epiphenomenon of comorbid
      depressive symptoms. The present study investigated whether the impact of
      comorbid depressive symptoms on cognitive dysfunction in OCD extends to nonverbal
      memory impairment. METHODS: A total of 32 OCD patients and 20 healthy controls
      took part in the study. Participants were administered a neurocognitive battery
      with a focus on nonverbal memory and visuospatial functions. RESULTS: While
      evidence was provided that neurocognitive processes necessitating visuospatial
      transformation and visuoconstruction are deficient in OCD patients regardless of
      comorbid depressive symptoms, nonverbal memory dysfunctions were only apparent
      for patients with elevated scores in the Hamilton Depression (HDRS) Rating Scale
      (total score > or = 8). Correlations with subscores of the HDRS revealed that
      core depressive symptoms are related to nonverbal memory deficits in OCD. Mental
      rotation, middle discrimination, and position discrimination were found to be
      unaffected in OCD. Y-BOCS scores, length of illness, onset of illness, number of
      hospital admissions, and checking compulsions were not associated with
      neurocognitive disturbances. CONCLUSIONS: Nonverbal memory is disturbed in only a
      subgroup of OCD patients displaying elevated HDRS scores (HDRS > or = 8). It is
      claimed but awaits further empirical testing that differences in depression
      profile across OCD studies have contributed to inconsistencies in prior
      investigations on neurocognitive functioning in OCD. Our results are questioning
      the hypothesis that nonverbal deficits are a causal factor for the development of
      checking compulsions.

PMID- 16571566
TI  - Line bisection performance in patients with personality disorders.
AB  - INTRODUCTION: Normal line bisection deviation to the left of the true centre has
      been interpreted as resulting from relative right hemisphere activation. Right
      hemisphere involvement has also been associated with the problems in dependency
      and attachment from infancy to adulthood. This hemispheric association predicts
      that patients diagnosed with dependent personality disorder will deviate
      significantly to the left on the line bisection task. METHODS: This hypothesis
      was tested by comparing the results of the line bisection task obtained
      respectively from 30 right-handed healthy volunteers and 14, 16, 18, and 26
      outpatients with schizotypal, antisocial, borderline, and dependent personality
      disorders. Subjects completed eight horizontal line bisection tasks and the
      Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ), a
      self-report measure of 18 traits delineating personality disorder. RESULTS:
      Patients with dependent personality disorder bisected significantly leftward
      compared to healthy controls. Dependent personality disorder patients scored
      significantly higher on DAPP-BQ Insecure Attachment, and lower on DAPP Stimulus
      Seeking, Callousness, Intimacy Problems, and Conduct Problems compared to the
      healthy controls and all other patient groups. CONCLUSIONS: Line bisection
      differentiates dependent personality disorder from other personality disorder
      diagnoses and healthy controls. This study thus suggests that line bisection can
      be used to enhance diagnostic specificity of dependent personality disorder and
      localises the brain areas implicated in the disorder.

PMID- 16571567
TI  - Attention, theory of mind, and causal attributions in people with persecutory
      delusions: A preliminary investigation.
AB  - INTRODUCTION: Abnormal attributions and deficits in theory of mind (ToM) skills
      have been implicated in paranoid delusions. Bentall and Kinderman (1998) have
      proposed that ToM deficits tend to prevent individuals from making situational
      attributions and therefore increase the probability of external-personal
      attributions, which in turn lead to paranoid beliefs. They further suggested that
      more fundamental information-processing deficits, by affecting theory of mind
      skills, increase the probability of paranoid attributions. METHODS: Relationships
      between attention, ToM and attributions were assessed in acute and remitted
      paranoid patients and normal controls. Participants performed the digit span with
      distraction task, false belief and deception tasks, and a measure of
      attributional style. RESULTS: Compared to the controls, acute patients were
      distractible, performed poorly on ToM, and made more attributions that were
      judged external-personal by independent raters (but not as judged by self
      ratings). ToM scores predicted the number of external-personal attributions as
      expected, but the effect of distraction on ToM was equivocal. CONCLUSIONS:
      Preliminary support was found for the hypotheses, but further studies are
      required using a range of executive, attentional, ToM, and attribution measures.

PMID- 16571570
TI  - Voices in the brain.

PMID- 16571568
TI  - Differential brain activations during intentionally simulated and subjectively
      experienced paralysis.
AB  - INTRODUCTION: Distinguishing conversion disorder from malingering presents a
      significant challenge as the diagnosis ultimately depends on the patient's
      subjective report and the clinician's suspicion of an intention to deceive. Using
      hypnosis to manipulate the intentionality of movement inhibition in the same
      subjects, we used positron emission tomography (PET) to determine whether failure
      to move during intentionally simulated and subjectively experienced paralysis is
      mediated by different neural structures. METHODS: Using a within-subject design,
      12 normal, hypnotised subjects were tested under two paralysis conditions during
      the same scanning session. Half of the scans were performed with the suggestion
      that the left leg was paralysed (subjectively experienced paralysis condition)
      and half with the leg normal but with the instruction that paralysis should be
      feigned (intentionally simulated paralysis condition). RESULTS: Relative
      increases in brain activation were seen in the right orbitofrontal cortex, right
      cerebellum, left thalamus, and left putamen during subjectively experienced
      paralysis compared to intentionally simulated paralysis, although a previously
      reported activation of the right anterior cingulate cortex was not seen. During
      intentionally simulated paralysis compared to subjectively experienced paralysis
      relative increases in brain activation were seen in the left ventrolateral
      prefrontal cortex, and a number of right posterior cortical structures.
      CONCLUSIONS: Our results suggest that subjectively experienced paralysis has a
      different neural basis to intentionally simulated paralysis. These findings have
      theoretical and clinical implications for malingering and related attempts to
      unravel the neuropsychological basis for conversion hysteria.

PMID- 16571571
TI  - Choices for voices: a voice hearer's perspective on hearing voices.

PMID- 16571572
TI  - Hearing voices: A phenomenological-hermeneutic approach.
AB  - The word "phenomenology" has a number of meanings. In this paper we briefly
      contrast the different meanings of the word in psychiatry and philosophy. We then
      consider the work of the philosophers Heidegger and Merleau-Ponty, as examples of
      what Hubert Dreyfus calls ontological phenomenology, in contrast to an
      epistemological approach. We present a brief outline of Merleau-Ponty's theory of
      embodiment, and contrast this with the dominant, epistemological (or Cartesian)
      view of experience. Through the example of a woman who experienced bereavement
      hallucinations, we try to show how this approach can open up a hermeneutic
      approach to the experience of hearing voices. An understanding of embodiment can
      help to counter reductionism, whether biological or social, and dualism
      (body/mind and mind/society). It is only when we consider the totality of human
      experience that we can understand its meaning. This has two main benefits. First,
      it legitimates the claims made by those who hear voices that their experiences
      are intrinsically meaningful. Second, it can provide a framework for those who
      work with voice hearers and who are interested in understanding these
      experiences. In this sense, phenomenology can become a valuable clinical tool.

PMID- 16571573
TI  - Psychological treatment for voices in psychosis.
AB  - Hearing voices is often one of the most distressing aspects associated with a
      diagnosis of psychosis. These voices are often resistant to medication
      treatments. This review article discusses the development of complementary
      approaches to the treatment of voices--psychological and particularly cognitive
      treatments. It is clear that there are psychological rather than merely physical
      factors associated with the occurrence of, and distress caused by, voices. These
      factors can be engaged in the process of psychological therapy in order to reduce
      the distress that they cause and improve quality of life. Psychological therapies
      have produced some improvements but very few have shown durable effects. Most
      psychological therapies have been individual with an emphasis on cognitive
      behavioural approaches. This paper describes the development of a new approach-
      group cognitive treatment--that might provide further success either as a single
      therapy for voices or as a complement to individual approaches. This type of
      therapy builds on the therapies and supports provided within the consumer
      movement as well as harnessing group and cognitive facilitators for change in
      beliefs. Some evidence is provided about the usefulness of such therapy in the
      health services. In addition, the evaluation of treatments for specific symptoms,
      particularly the appropriate outcome measures is discussed.

PMID- 16571574
TI  - Compelling imagery, unanticipated speech and deceptive memory: neurocognitive
      models of auditory verbal hallucinations in schizophrenia.
AB  - INTRODUCTION: The application of neurocognitive models to study schizophrenia has
      been influential in understanding the nature of this complex and heterogeneous
      disorder. However, a comprehensive and empirically validated account of auditory
      hallucinations remains elusive. The aim of this review was to critically assess
      the current evidence for specific neurocognitive deficits associated with
      auditory verbal hallucinations (AVHs) in schizophrenia. METHODS: A systematic
      literature search was conducted of research involving three influential cognitive
      models of auditory hallucinations: those implicating dysfunction in auditory
      imagery, verbal self-monitoring, and episodic memory. RESULTS: The findings of
      the review suggested that AVHs have been associated with impaired verbal self
      monitoring, impaired memory for self-generated speech, heightened influence of
      top-down processing on perception, and an externalising response bias.
      CONCLUSIONS: On the basis of the findings of the review a multidimensional model
      of AVHs is proposed incorporating the identified cognitive deficits and biases.

PMID- 16571575
TI  - Auditory hallucinations: Insights and questions from neuroimaging.
AB  - INTRODUCTION: The human brain has the capacity to hallucinate but rarely, except
      in severe neuropsychiatric conditions such as schizophrenia, do they naturally
      predominate. The neural basis of auditory verbal hallucinations (AVHs) has been
      investigated using structural and functional neuroimaging techniques. So far, no
      studies have defined a model that explains why auditory hallucinations are
      perceived in the absence of an external stimulus. METHODS: A selective literature
      review was undertaken specifically to focus on: (1) clinical phenomenology; (2)
      putative brain systems involved in the pathogenesis of auditory hallucinations as
      suggested by neuroimaging studies; (3) contributions and weaknesses of the
      neuroimaging findings in potentially bridging the gap between the neuroscience
      and phenomenology. Throughout, an attempt was made to ask questions as much as to
      answer them. RESULTS: Functional domains implicated in the genesis of auditory
      verbal hallucinations include: (1) hearing and language; (2) "sense of reality",
      including externality of voices; (3) attention and salience; (4) emotional
      response; (5) memory; (6) volition and self-monitoring; (7) impulse control. Each
      of these domains can be mapped onto neural "systems" that comprise components
      that overlap with brain regions known to activate during the experience of
      auditory hallucinations. CONCLUSIONS: In the next phase of neuroimaging research
      into the pathogenesis of auditory hallucinations we need to examine component
      processes that lead to the patient's perception of them as real.

PMID- 16571577
TI  - The cognitive neuropsychiatry of auditory verbal hallucinations: an overview.
AB  - INTRODUCTION: The cognitive neuropsychiatric approach to auditory verbal
      hallucinations (AVHs) attempts to explain the phenomena in cognitive or
      information-processing terms and ultimately their brain bases. METHODS: A
      narrative review of the literature and an overview of this special issue of
      Cognitive Neuropsychiatry. RESULTS: First, an operational definition of AVHs is
      offered. Next, clues to etiology are derived from a detailed consideration of the
      clinical phenomenology of "voices", their form and content. Functional and
      structural neuroimaging studies suggest the importance of left-side language
      areas in the generation/perception of AVHs. CONCLUSIONS: Existing cognitive
      neuropsychiatric models provide a useful framework for the understanding of AVHs.
      However, data need to be applied more specifically to these models so that they
      may be refined.

PMID- 16571576
TI  - Locating voices in space: a perceptual model for auditory hallucinations?
AB  - INTRODUCTION: Auditory hallucinations are often perceived as being located in
      external auditory space ("outside the head"), like real auditory perceptions, but
      in the absence of a speaker or other external stimulus. METHOD: A selective
      literature review of the spatial phenomenology of auditory hallucinations and the
      cognitive neuroscience of locating real voices in external space was undertaken.
      An auditory-perceptual model of external auditory hallucinations was developed in
      healthy right-handed subjects using functional magnetic resonance imaging and the
      presentation of speech in virtual acoustic space. RESULTS: Karl Jaspers
      inextricably linked "reality" and "externality" of auditory hallucinations.
      Although these two properties do not always occur simultaneously in hallucinating
      patients, the issue of "externality" is important from both a clinical and
      neuroscientific perspective. In an auditory-perceptual model of auditory
      hallucinations, association cortex in the left planum temporale is critically
      involved in the perception of real voices as located in external space. Right
      sided voice stimuli are associated with greater neural response in the dominant
      (left) auditory cortex than left-sided stimuli. Subjects are better at
      identifying the spatial location of voices presented on the right than on the
      left. CONCLUSION: The auditory-perceptual model described helps identify
      candidate brain systems likely to be involved in the pathogenesis of auditory
      hallucinations in schizophrenia, and is distinct from other models, which use
      concepts of "internal monitoring" and "inner speech". Its application, in the
      cognitive neuroscientific investigation of the phenomenology of auditory
      hallucinations, may shed further light on the mechanisms underlying this
      distressing experience.

PMID- 16571578
TI  - Auditory hallucinations as primary disorders of syntax: an evolutionary theory of
      the origins of language.
AB  - A theory of the evolutionary origins of language is built around: (1) the notion
      that language is a sapiens-specific capacity that arose in the speciation event
      that separated modern Homo sapiens from a prior hominid species, and (2) Broca's
      concept of asymmetry (subsequently recognised as a "torque" from right frontal to
      left occipital cortices) as the defining characteristic of the human brain. The
      four chambers of human association cortex thus created allow the separation of
      "thought" from the speech output and "meaning" from the speech input, these
      abstractions representing the associations in the nondominant hemisphere of the
      motor and sensory phonological representations in the dominant hemisphere. The
      nuclear symptoms of schizophrenia are conceived as manifestations of the
      breakdown of the boundaries between these four compartments, and as indicating
      the necessity of the separation of motor and sensory speech engrams as the basis
      for the speaker-hearer distinction. They further illustrate a requirement for a
      "deictic core" to the cerebral organisation of language as Mueller and Buehler
      proposed. In this sense the nuclear symptoms are disorders of the syntax of
      universal grammar.

PMID- 16571579
TI  - Comprehension, encoding, and monitoring in the production of confabulation in
      memory: a study with schizophrenic patients.
AB  - INTRODUCTION: The aim of the present study was to test the hypotheses proposed by
      Nathaniel-James and collaborators (Nathaniel-James & Frith, 1996; Nathaniel
      James, Foong, & Frith, 1996) to account for the cognitive deficits involved in
      the production of confabulations in schizophrenic patients: impairments in
      comprehension, memory encoding, and memory monitoring. METHOD: Five patients were
      investigated in this multiple single-case study. Comprehension abilities were
      investigated in several tests in which a memory bias was avoided. The encoding
      deficit hypothesis was tested by manipulating cues at encoding and/or retrieval.
      "Memory monitoring" abilities were examined in two tasks: the Hayling test for
      all patients and an AB-AC word pairs learning task for two patients. RESULTS:
      Four of the patients produced an abnormal level of confabulations in story and
      fable learning tests. All patients exhibited encoding deficits and specific
      comprehension difficulties. However, some demonstrated preserved memory
      monitoring abilities. Across different tests, it was observed that the more the
      confabulations occurred, the more severe were the comprehension difficulties.
      CONCLUSION: The results are in favour of the hypothesis that verbal comprehension
      difficulties lead to the production of confabulation. They are inconsistent with
      the idea that memory monitoring impairment is necessarily involved.

PMID- 16571580
TI  - Self-recognition in everyday life.
AB  - INTRODUCTION: A sample of everyday difficulties was collected, encompassing
      errors and unusual experiences participants had encountered when recognising
      their own faces in everyday life, with the aim of characterising similarities and
      differences between the reported difficulties and the major forms of self
      recognition impairments described in the neuropsychological and neuropsychiatric
      literatures (prosopagnosia, mirrored-self misidentification, and Capgras
      delusion). METHOD: A total of 70 participants recalled experiences from memory.
      Incidents (n = 51) were recorded on questionnaire sheets that were filled out at
      home. Reports of three categories of incidents were analysed: misidentifications
      (the participant misidentified her/his own face as being that of another familiar
      person; n = 5), recognition failures (the participant judged that his/her own
      face was that of an unfamiliar person; n = 20) and perception of unusual aspects
      (the participant confidently recognised his/her own face but found that the seen
      face did not fit well the representation she/he had of his/her own face; n = 26).
      RESULTS AND DISCUSSION: In the reported incidents, experiences showing some
      similarities to those of patients with prosopagnosia, Capgras delusion or
      mirrored-self misidentification were noted. However, across the whole study, no
      incident involved a failure of reality testing; in contrast to pathological forms
      of error, in all of the reported incidents from our study the participant
      realised that a mistake had been made. The importance of decision processes in
      pathological forms of own-face misrecognition is discussed.

PMID- 16571581
TI  - Effects of neurocognitive enhancement therapy in schizophrenia: normalisation of
      memory performance.
AB  - INTRODUCTION: A preponderance of research indicates that cognitive function in
      schizophrenia can be improved through cognitive remediation. However, few studies
      have attempted to characterise the extent of improvement relative to
      nonpsychiatric controls. METHOD: Cognitive performance on reaction time, digit
      recall, and word recall of 58 schizophrenia patients at baseline and after 6
      months of cognitive remediation was compared to the performance on these tasks of
      39 community controls. Schizophrenia patients participated in Neurocognitive
      Enhancement Therapy (NET) and received hierarchical training on the memory tasks,
      but not on the reaction time task, which was only administered at intake and
      follow-up. RESULTS: The schizophrenia sample showed significantly poorer
      performances than the community control sample on all three tasks at baseline.
      NET led to significant improvements in performance on trained memory tasks, but
      not the untrained reaction time task. There was a significant increase in the
      proportion of schizophrenia patients who achieved normal range performance on the
      memory tasks. CONCLUSIONS: 52% of schizophrenia patients who were impaired on at
      least one of the memory tasks normalised their performance on at least one of
      those tasks as a result of cognitive training. Results suggest that clinically
      meaningful improvement may be possible using cognitive remediation.

PMID- 16571582
TI  - Material-specific episodic memory associates of the psychomotor poverty syndrome
      in schizophrenia.
AB  - INTRODUCTION: Episodic memory deficits consistently correlate with the presence
      of negative symptoms in schizophrenia, suggesting overlap between the underlying
      neural systems. Functional neuroimaging and lesion studies suggest that
      prefrontal hypoactivity may underlie both. The purpose of the present study was
      to further characterise this association in terms of functional lateralisation. A
      more pronounced association between psychomotor poverty and verbal memory
      deficits would suggest more left prefrontal overlap than right, and vice-versa
      for a more pronounced association with nonverbal memory deficits. METHODS: A
      total of 68 inpatients (48 males, 20 females) diagnosed with schizophrenia or
      schizoaffective disorder participated in this study. We evaluated the correlation
      between verbal and nonverbal memory performance (assessed using the RAVLT and
      BVMT, respectively) and psychomotor poverty (assessed using the SSPI). RESULTS: A
      trend towards a more pronounced association for nonverbal compared to verbal
      material was not upheld by conservative statistical testing. CONCLUSIONS:
      Bilateral prefrontal overlap between psychomotor poverty and episodic memory is
      the most conservative interpretation of these data.

PMID- 16571584
TI  - Speed of processing and individual differences in IQ in schizophrenia: General or
      specific cognitive deficits?
AB  - INTRODUCTION: The aim of this study was to re-examine the role of cognitive
      processing speed in the vulnerability to schizophrenia, using an inspection time
      (IT) task that does not require a speeded manual response. Since IT consistently
      correlates with intelligence, the relationship between IT and general
      intelligence was also explored. METHODS: Patients with schizophrenia were
      compared with unaffected siblings of schizophrenia patients and healthy controls
      on a visual IT task. Both speed and variability of IT performance were examined.
      Current intellectual ability (IQ) was estimated with the Shipley Institute of
      Living Scale (SILS), which yields separate assessments of verbal and abstraction
      abilities. RESULTS: Schizophrenia patients produced ITs that were significantly
      slower and more variable than either unaffected siblings or healthy controls.
      These results are not related to demographic or clinical variables. A significant
      negative correlation was obtained between IT and IQ; specifically, longer IT
      values were associated with abstraction scores only. CONCLUSIONS: These findings
      confirm that basic cognitive processing efficiency is impaired in patients with
      schizophrenia. In contrast, ITs in unaffected siblings did not differ from
      healthy controls, in line with their better IQ test scores. Implications for
      models of general and specific heritable dimensions in schizophrenia are
      discussed.

PMID- 16571585
TI  - Unstable identity and prefrontal injury.
AB  - INTRODUCTION: In neuropsychological research, "organic personality disorder",
      lack of social insight, and executive dysfunctions have been identified in
      patients with prefrontal brain injury. The assessment of personality change has,
      in particular, been a methodological challenge in this field of research. The aim
      of the present pilot study was to examine personality aspects in patients with
      prefrontal brain injury from a neuropsychological as well as a psychodynamic
      point of view. METHODS: A total of 13 adults with personality change as a
      manifest sequel after sudden onset brain injury were assessed with
      neuropsychological tests of executive functions, with the European Brain Injury
      Questionnaire (EBIQ), and with the Karolinska Psychodynamic Profile (KAPP), which
      to our knowledge has not previously been used as part of a neuropsychological
      assessment. The personality profiles of the brain-injured patients were compared
      to the personality profile of a group of 65 brain-healthy individuals. RESULTS:
      The personality organisation of the prefrontally brain-injured patients was
      significantly disturbed and close to a borderline personality organisation, as
      defined by the KAPP. CONCLUSIONS: The results of the pilot study suggest that
      prefrontal brain systems may support the integration of self-functions and play a
      central role for inter-personal relations. Future research regarding the relation
      between brain dysfunction, executive and cognitive deficit, and personality
      disorder needs to be carried out in larger samples to substantiate the hypothesis
      of a relationship between prefrontal brain systems and self-functions.

PMID- 16571586
TI  - An early marker for semantic memory impairment in patients with schizophrenia.
AB  - INTRODUCTION: Semantic memory impairment is now a well-documented phenomenon in
      patients with schizophrenia. Nevertheless, the characteristics of this deficit
      and any early markers remain contentious. METHODS: In this preliminary study, 12
      schizophrenic patients underwent longitudinal assessment using a battery of
      semantic memory tests. Patient performance was compared to 12 matched controls.
      Using set criteria (derived from Warrington & Shallice, 1979), we examined
      whether the patients had a disorder affecting access to intact representations,
      or a degradation/loss of the representations themselves. The criteria were:
      consistency across time and modality, level of attribute information, and
      responsiveness to cueing. Finally, we compared patient naming for the same items
      across two naming tests (naming-to-description and picture naming) to determine
      cross-modality consistency. RESULTS: As expected, normal controls outperformed
      the patients on all tests. Naming-to-description was the most significant
      differentiator between patients and controls. Patients were inconsistent across
      both time and modality, showed minimal attributional knowledge impairment, and
      improved significantly with cueing on two naming tests. CONCLUSION: The profile
      of results indicates an access-type semantic deficit in this cohort of patients
      with schizophrenic. Finally, on a naming-to-description task, the patients failed
      to name up to 20% of items that they could name to picture. This suggests that
      naming-to-definition may act as an early marker of semantic memory impairment.

PMID- 16571587
TI  - Spatial characteristics of hallucinations associated with sleep paralysis.
AB  - INTRODUCTION: Spatial properties of hallucinations have received relatively
      little systematic investigation. We present evidence from a web-based study of
      the spatial properties of a broad array of hallucinations associated with sleep
      paralysis. Predictions regarding spatial characteristics of hallucinations were
      based on proposed neurophysiological mechanisms underlying different types of
      hallucinations. METHOD: Distributions in three dimensions as well as distance and
      dispersion measures were assessed for 279 experient for two general categories of
      hallucinations: Intruder hallucinations--including presence, visual, and auditory
      hallucinations; and Vestibular-Motor (V-M) hallucinations--including floating,
      flying, illusory motor movements, out-of-body experiences (OBEs), and autoscopy.
      RESULTS: For all spatial measures, Confirmatory Factor Analysis revealed that
      Intruder and V-M hallucinations constituted distinctive factors. In addition,
      Intruder hallucinations were experienced as occurring close to, usually within a
      meter of, the experient, whereas V-M hallucinations involved excursions of
      considerable distance, often beyond the immediate environment. V-M hallucination
      distance was positively associated with vividness of V-M hallucinations, whereas
      Intruder hallucination distance was negatively correlated with theoretically
      related contact hallucinations (pressure, obstructed breathing, pain, choking,
      and touch). CONCLUSION: The differences in the spatial characteristics of
      Intruder and V-M hallucinations largely corroborated predictions based on the
      respective hypothesised neural substrates of a threat activated vigilance system
      and a bodily-self neuromatrix.

PMID- 16571588
TI  - Inference of mental states in patients with Alzheimer's disease.
AB  - INTRODUCTION: The ability to determine what someone thinks or knows often
      requires an individual to infer the mental state of another person, an ability
      typically referred to as one's "theory of mind". The present study tests this
      ability in patients with mild-to-moderate Alzheimer's disease (AD). METHODS:
      Three theory of mind tests and three standardised neuropsychological tests were
      presented to a group of patients with AD (n = 25) and a group of healthy elderly
      controls (n = 15). RESULTS: On the first two theory of mind tasks, the
      performance of the AD patients was nearly perfect and did not differ from that of
      the controls: AD patients showed no difficulties in either attributing a false
      belief to another person, or in recognising their own previous false beliefs. On
      the third theory of mind task, where the key information was embedded in a story
      narrative, AD patients per formed significantly worse than controls. However,
      their performance on this task was similar to the control condition, which used a
      similar story but which did not involve beliefs. CONCLUSIONS: These results, as
      well as those involving correlations between the neuropsychological tests and
      performance on the third task, suggest that the AD patients' difficulty may be
      secondary to their cognitive impairments, rather than a primary impairment in
      theory of mind.

PMID- 16571591
TI  - Acute effects of environmental tobacco smoke and dried dung smoke on lung
      histopathology in rabbits.
AB  - AIMS: To compare the effects of cigarette smoke and dried dung smoke exposure on
      the histopathology of lungs. METHODS: Three groups each with five rabbits were
      formed. The cigarette smoke group was exposed to cigarette smoke, the biomass
      group was exposed to dried dung smoke and the control group was exposed to dry
      air 1 hour daily for 1 month. At the end of 1 month, animals were sacrificed and
      lung tissues were examined histopathologically. RESULTS: Histopathological
      evaluation of rabbits' lungs revealed that intraparenchymal vascular congestion
      and thrombosis, intraparenchymal haemorrhage, respiratory epithelial
      proliferation, number of macrophages in the alveolar and bronchial lumen,
      alveolar destruction, emphysematous changes and bronchoalveolar haemorrhage
      scores were significantly increased in rabbits exposed to cigarette smoke
      compared with the control group. Respiratory epithelial proliferation, alveoli
      destruction and emphysematous change scores were significantly increased in
      rabbits exposed to dried dung smoke compared with the control group. CONCLUSION:
      Although less than the effects of cigarette smoke, dried dung smoke had severe
      histopathological effects on rabbits' lungs.

PMID- 16571592
TI  - Mesangial cells initiate compensatory renal tubular hypertrophy via IL-10-induced
      TGF-beta secretion: effect of the immunomodulator AS101 on this process.
AB  - The present study investigated the role of IL-10 produced by the mesangial cells
      in postnephrectomy compensatory renal growth and the effect of the
      immunomodulator AS101 on this process. One hundred forty unilateral
      nephrectomized and sham-operated male Sprague-Dawley rats were treated by AS101
      or PBS before and after surgery. The results show that secretion of IL-10 and TGF
      beta by mesangial cells isolated from the remaining kidneys was increased
      significantly, compared with those of control and sham animals. Moreover, TGF
      beta secretion by mesangial cells was increased after the addition of exogenous
      recombinant IL-10 and inhibited in the presence of neutralizing anti-IL-10
      antibodies. In vivo, compensatory growth of the remaining kidneys was associated
      with significant increase in IL-10 content in renal tissues and plasma.
      Immunohistochemical studies show that IL-10 was produced by mesangial cells.
      Elevated IL-10 levels were followed by the rise in TGF-beta content in plasma and
      renal tissue. AS101 treatment decreased IL-10 and TGF-beta expression in plasma
      and kidney tissues and results in 25% reduction in the fresh and fractional
      kidney weight and decreased hypertrophy of tubular cells (protein/DNA ratio,
      morphometric analysis). Taken together, these data demonstrate that TGF-beta
      production by mesangial cells is IL-10 dependent. Mesangial cells are the major
      source of IL-10 in kidneys. AS101, by inhibiting the activity of IL-10, decreases
      TGF-beta production by mesangial cells, thus limiting compensatory tubular cell
      hypertrophy.

PMID- 16571593
TI  - Amino acids as modulators of endothelium-derived nitric oxide.
AB  - To examine the mechanisms whereby amino acids modulate nitric oxide (NO)
      production and blood flow in the renal vasculature, chemiluminescence techniques
      were used to quantify NO in the renal venous effluent of the isolated, perfused
      rat kidney as different amino acids were added to the perfusate. The addition of
      10(-4) or 10(-3) M cationic amino acids (l-ornithine, l-lysine, or l
      homoarginine) or neutral amino acids (l-glutamine, l-leucine, or l-serine) to the
      perfusate decreased NO and increased renal vascular resistance. Perfusion with
      anionic amino acids (l-glutamate or l-aspartate) had no effect on either
      parameter. The effects of the cationic and neutral amino acids were reversed with
      10(-3) M l-arginine and prevented by deendothelialization or NO synthase
      inhibition. The effects of the neutral amino acids but not the cationic amino
      acids were dependent on extracellular sodium. Cationic and neutral amino acids
      also decreased calcimycin-induced NO, as assessed by DAF-FM-T fluorescence, in
      cultured EA.hy926 endothelial cells. Inhibition of system y(+) or y(+)L by siRNA
      for the cationic amino acid transporter 1 or the CD98/4F2 heavy chain diminished
      the NO-depleting effects of these amino acids. Finally, transport studies in
      cultured cells demonstrated that cationic or neutral amino acids in the
      extracellular space stimulate efflux of l-arginine out of the cell. Thus the
      present experiments demonstrate that cationic and neutral amino acids can
      modulate NO production in endothelial cells by altering cellular l-arginine
      transport through y(+) and y(+)L transport mechanisms.

PMID- 16571595
TI  - Renal endothelial dysfunction and impaired autoregulation after ischemia
      reperfusion injury result from excess nitric oxide.
AB  - Endothelial dysfunction in ischemic acute renal failure (IARF) has been
      attributed to both direct endothelial injury and to altered endothelial nitric
      oxide synthase (eNOS) activity, with either maximal upregulation of eNOS or
      inhibition of eNOS by excess nitric oxide (NO) derived from iNOS. We investigated
      renal endothelial dysfunction in kidneys from Sprague-Dawley rats by assessing
      autoregulation and endothelium-dependent vasorelaxation 24 h after unilateral (U)
      or bilateral (B) renal artery occlusion for 30 (U30, B30) or 60 min (U60, B60)
      and in sham-operated controls. Although renal failure was induced in all degrees
      of ischemia, neither endothelial dysfunction nor altered facilitation of
      autoregulation by 75 pM angiotensin II was detected in U30, U60, or B30 kidneys.
      Baseline and angiotensin II-facilitated autoregulation were impaired,
      methacholine EC(50) was increased, and endothelium-derived hyperpolarizing factor
      (EDHF) activity was preserved in B60 kidneys. Increasing angiotensin II
      concentration restored autoregulation and increased renal vascular resistance
      (RVR) in B60 kidneys; this facilitated autoregulation, and the increase in RVR
      was abolished by 100 microM furosemide. Autoregulation was enhanced by N(omega)
      nitro-l-arginine methyl ester. Peri-ischemic inhibition of inducible NOS
      ameliorated renal failure but did not prevent endothelial dysfunction or impaired
      autoregulation. There was no significant structural injury to the afferent
      arterioles with ischemia. These results suggest that tubuloglomerular feedback is
      preserved in IARF but that excess NO and probably EDHF produce endothelial
      dysfunction and antagonize autoregulation. The threshold for injury-producing,
      detectable endothelial dysfunction was higher than for the loss of glomerular
      filtration rate. Arteriolar endothelial dysfunction after prolonged IARF is
      predominantly functional rather than structural.

PMID- 16571594
TI  - Roles of cytosolic and membrane-bound carbonic anhydrase in renal control of acid
      base balance in rainbow trout, Oncorhynchus mykiss.
AB  - We tested the hypothesis that cytosolic and membrane-associated carbonic
      anhydrase (CA IV) are involved in renal urinary acidification and bicarbonate
      reabsorption in rainbow trout. With the use of homological cloning techniques, a
      1,137-bp cDNA was assembled that included an open reading frame encoding for a
      deduced protein of 297 amino acids. Phylogenetic analysis revealed that this
      protein was likely a CA IV isoform. With the use of this sequence and a
      previously described trout cytosolic isoform [tCAc (13)], tools were developed to
      quantify and localize mRNA and protein for the two CA isoforms. Unlike tCAc,
      which displayed a broad tissue distribution, trout CA IV mRNA (and to a lesser
      extent protein) was highly and preferentially expressed in the posterior kidney.
      The results of in situ hybridization, immunocytochemistry, and standard
      histological procedures demonstrated that CA IV was likely confined to epithelial
      cells of the proximal tubule with the protein being expressed on both apical and
      basolateral membranes. The CA IV-containing tubule cells were enriched with Na(+)
      K(+)-ATPase. Similar results were obtained for tCAc except that it appeared to be
      present in both proximal and distal tubules. The levels of mRNA and protein for
      tCAc increased significantly during respiratory acidosis (hypercapnia). Although
      tCA IV mRNA was elevated after 24 h of hypercapnia, tCA IV protein levels were
      unaltered. By using F3500, a membrane-impermeant (yet filtered) inhibitor of CA,
      in concert with blood and urine analyses, we demonstrated that CA IV (and
      possibly other membrane-associated CA isoforms) plays a role in urinary
      acidification and renal bicarbonate reabsorption.

PMID- 16571597
TI  - Lithium treatment and remodeling of the collecting duct.

PMID- 16571596
TI  - Mice heterozygous for beta-ENaC deletion have defective potassium excretion.
AB  - The present studies were designed to determine whether mice heterozygous for
      deletion of beta-ENaC exhibited defects in Na+/K+ transport and blood pressure
      regulation. In response to an acute KCl infusion, +/-mice developed higher serum
      [K+] and excreted only 40% of the K+ excreted by +/+mice. After 6 days on a low
      (0.01%)-Na+ diet, the cumulative Na+ excretion from days 3-6 was greater for +/
      mice. This low-Na+ diet caused higher serum [K+] and lower K+ excretion rates in
      +/-mice than in +/+mice, but the rectal potential differences were not different.
      Analyses of mRNA from mice on this diet showed the expected approximately 50%
      reduction of beta-ENaC in kidney and colon of +/-mice. Unexpectedly, the level of
      gamma-ENaC mRNA was similarly reduced. NHE3 mRNA was approximately 30% higher in
      +/-mice whereas mRNA of the Na-K-2Cl cotransporter was not different. Also
      unexpectedly, the amount of beta-ENaC proteins was similar in both groups of mice
      but there was a reduction of one form of gamma-ENaC in +/-mice. These experiments
      demonstrate that mice heterozygous for beta-ENaC have a small but detectable
      defect in their ability to conserve Na+ and a more readily apparent defect in the
      ability to secrete K+.

PMID- 16571598
TI  - Susceptibility to metanephric apoptosis in bradykinin B2 receptor null mice via
      the p53-Bax pathway.
AB  - In response to gestational high salt intake, BdkrB2-/- embryos acquire an
      aberrant renal phenotype mimicking renal dysplasia in humans. Genetic analysis
      identified p53 as a mediator of the renal dysplasia in salt-stressed BdkrB2-/-
      mice, acting partly via repression of terminal epithelial differentiation genes.
      The present study tested the hypothesis that inactivation of BdkrB2 predisposes
      the salt-stressed embryo to p53-mediated metanephric apoptosis. Newborn BdkrB2-/-
      pups exhibited hyperphosphorylation of metanephric p53 on serine 20 (mouse serine
      23), a modification known to increase p53 stability and apoptotic activity. As a
      result, there was widespread, ectopic expression of p53 in the BdkrB2-/- kidney.
      However, no differences were found in the apoptosis index or gene expression in
      BdkrB2-/- and +/+ kidneys, indicating that p53 stabilization as a result of
      BdkrB2 inactivation is not sufficient to induce metanephric apoptosis. On
      gestational salt stress, fulminant metanephric apoptosis and enhanced Bax gene
      expression occurred in BdkrB2-/- but not their +/- or +/+ littermates. Germline
      deletion of p53 from BdkrB2-/- mice prevented Bax activation and normalized the
      apoptosis index. Rescue of metanephric apoptosis in BdkrB2-/- mice was similarly
      achieved by Bax gene deletion. Aberrant apoptosis in salt-stressed BdkrB2-/- mice
      was triggered on embryonic day E15.5 and involved both ureteric bud (UB) and
      metanephric mesenchyme-derived nephron elements. Cultured E12.5 salt-stressed
      BdkrB2-/- metanephroi manifested stunted UB branching compared with +/- and +/+
      littermates; the abnormal UB branching was corrected by p53 deletion. Our results
      suggest a model whereby a seemingly silent genetic mutation of BdkrB2 predisposes
      mice to renal dysplasia by creating a "preapoptotic" state through p53
      activation.

PMID- 16571599
TI  - WFS1-deficiency increases endoplasmic reticulum stress, impairs cell cycle
      progression and triggers the apoptotic pathway specifically in pancreatic beta
      cells.
AB  - Wolfram syndrome, an autosomal recessive disorder associated with diabetes
      mellitus and optic atrophy, is caused by mutations in the WFS1 gene encoding an
      endoplasmic reticulum (ER) membrane protein. Herein, we report that pancreatic
      islets of wfs1-deficient mice exhibit increases in phosphorylation of RNA
      dependent protein kinase-like ER kinase, chaperone gene expressions and active
      XBP1 protein levels, indicating an enhanced ER stress response. We established
      wfs1-deficient MIN6 clonal beta-cells by crossing wfs1-deficient mice with mice
      expressing simian virus 40 large T antigen in beta-cells. These cells show
      essentially the same alterations in ER stress responses as wfs1-deficient islets,
      which were reversed by re-expression of WFS1 protein or overexpression of GRP78,
      a master regulator of the ER stress response. In contrast, these changes are not
      observed in heart, skeletal muscle or brown adipose tissues with WFS1-deficiency.
      The increased ER stress response was accompanied by reduced BrdU incorporation
      and increased caspase-3 cleavage, indicating impaired cell cycle progression and
      accelerated apoptotic processes in the mutant islets. These changes are
      associated with increased expression of the cell cycle regulator p21(CIP1) in
      wfs1-deficient islets and clonal beta-cells. Treatment of islets with
      thapsigargin, an ER stress inducer, caused upregulation of p21(CIP1). In
      addition, forced expression of p21(CIP1) resulted in reduced MIN6 beta-cell
      numbers, suggesting the ER stress-induced increase in p21(CIP1) expression to be
      involved in beta-cell loss in the mutant islets. These data indicate that WFS1
      deficiency activates the ER stress response specifically in beta-cells, causing
      beta-cell loss through impaired cell cycle progression and increased apoptosis.

PMID- 16571600
TI  - Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9
      and contributes to rapid neurodegeneration in INCL.
AB  - The infantile neuronal ceroid lipofuscinosis (INCL), a rare (one in 100 000
      births) but one of the most lethal inherited neurodegenerative storage disorders
      of childhood, is caused by inactivating mutations in the palmitoyl-protein
      thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in s-acylated
      (palmitoylated) proteins and facilitates their degradation and/or recycling.
      Thus, PPT1-deficiency leads to an abnormal intracellular accumulation of s
      acylated proteins causing INCL pathogenesis. Although neuronal apoptosis is the
      suggested cause of neurodegeneration in this disease, the molecular mechanism(s)
      remains poorly understood. We recently reported that one of the major pathways of
      neuronal apoptosis in PPT1-knockout (PPT1-KO) mice that mimic INCL, is mediated
      by endoplasmic reticulum (ER) stress-induced caspase-12 activation. ER stress
      also increases the production of reactive oxygen species (ROS), disrupts Ca(2+)
      homeostasis and increases the potential for destabilizing mitochondrial membrane.
      Mitochondrial membrane destabilization activates caspase-9 present in this
      organelle, and can mediate apoptosis. We report here that the levels of
      superoxide dismutase (SOD), most likely induced by ROS, in human INCL as well as
      PPT1-KO mouse brain tissues are markedly elevated. Moreover, we demonstrate that
      activated caspase-3 and cleaved-PARP, indicative of apoptosis, are also increased
      in these tissues. Using cultured neurospheres from PPT1-KO and wild-type mouse
      fetuses, we further demonstrate that the levels of ROS, SOD-2, cleaved-caspase-9,
      activated caspase-3 and cleaved-PARP are elevated. We propose that: (i) ER stress
      due to PPT1-deficiency increases ROS and disrupts calcium homeostasis activating
      caspase-9 and (ii) caspase-9 activation mediates caspase-3 activation and
      apoptosis contributing to rapid neurodegeneration in INCL.

PMID- 16571601
TI  - Effect of mutations in the PCSK9 gene on the cell surface LDL receptors.
AB  - The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is involved in the
      post-transcriptional regulation of the low-density lipoprotein (LDL) receptors
      (LDLR). Mutations in the PCSK9 gene have been associated with both
      hypocholesterolemia and hypercholesterolemia through 'loss-of-function' and 'gain
      of-function' mechanisms, respectively. We have studied the effect of the four
      loss-of-function mutations R46L, G106R, N157K and R237W and the two gain-of
      function mutations S127R and D374Y on the autocatalytic activity of PCSK9, as
      well as on the amount of the cell surface LDLR and internalization of LDL in
      transiently transfected HepG2 cells. The two groups of mutations did not differ
      with respect to autocatalytic activity of PCSK9, but they did differ with respect
      to the amount of cell surface LDLR and internalization of LDL. The four loss-of
      function mutations had a 16% increased level of cell surface LDLR and a 35%
      increased level of internalization of LDL as compared with WT-PCSK9. The two gain
      of-function mutations had a 23% decreased level of cell surface LDLR and a 38%
      decreased level of internalization of LDL as compared with WT-PCSK9. Our studies
      have also shown that transfer of media from transiently transfected HepG2 cells
      to untransfected HepG2 cells, reduces the amount of cell surface LDLR and
      internalization of LDL in the untransfected cells within 20 min of media
      transfer. Thus, PCSK9 or a factor acted upon by PCSK9, is secreted from the
      transfected cells and degrades LDLR both in transfected and untransfected cells.

PMID- 16571602
TI  - The nuclear microspherule protein 58 is a novel RNA-binding protein that
      interacts with fragile X mental retardation protein in polyribosomal mRNPs from
      neurons.
AB  - The fragile X syndrome, the leading cause of inherited mental retardation, is due
      to the inactivation of the fragile mental retardation 1 gene (FMR1) and the
      subsequent absence of its gene product FMRP. This RNA-binding protein is thought
      to control mRNA translation and its absence in fragile X cells leads to
      alteration in protein synthesis. In neurons, FMRP is thought to repress specific
      mRNAs during their transport as silent ribonucleoparticles (mRNPs) from the cell
      body to the distant synapses which are the sites of local synthesis of neuro
      specific proteins. The mechanism by which FMRP sorts out its different mRNAs
      targets might be tuned by the intervention of different proteins. Using a yeast
      two-hybrid system, we identified MicroSpherule Protein 58 (MSP58) as a novel FMRP
      cellular partner. In cell cultures, we found that MSP58 is predominantly present
      in the nucleus where it interacts with the nuclear isoform of FMRP. However, in
      neurons but not in glial cells, MSP58 is also present in the cytoplasmic
      compartment, as well as in neurites, where it co-localizes with FMRP. Biochemical
      evidence is given that MSP58 is associated with polyribosomal poly(A)+ mRNPs. We
      also show that MSP58, similar to FMRP, is present on polyribosomes prepared from
      synaptoneurosomes and that it behaves as an RNA-binding protein with a high
      affinity to the G-quartet structure. We propose that this novel cellular partner
      for FMRP escorts FMRP-containing mRNP from the nucleus and nucleolus to the
      somato-dendritic compartment where it might participate in neuronal translation
      regulation.

PMID- 16571603
TI  - Association of alcohol dehydrogenase genes with alcohol dependence: a
      comprehensive analysis.
AB  - Linkage evidence indicated that gene(s) located on chromosome 4q, in the region
      of the alcohol dehydrogenase (ADH) genes, affected risk for alcoholism. We
      genotyped 110 single nucleotide polymorphisms (SNPs) across the seven ADH genes
      and analyzed their association with alcoholism in a set of families with multiple
      alcoholic members, using the pedigree disequilibrium test. There was strong
      evidence that variations in ADH4 are associated with alcoholism: 12 SNPs were
      significantly associated. The region of strongest association ran from intron 1
      to 19.5 kb beyond the 3' end of the gene. Haplotype tag SNPs were selected for
      the block in the ADH4 gene that provided evidence of association and subsequently
      used in association analysis; the haplotype was significantly associated with
      alcoholism (P=0.01) There was weaker evidence that variations in ADH1A and ADH1B
      might also play a role in modifying risk. Among African-Americans, there was
      evidence that the ADH1B*3 allele was protective.

PMID- 16571604
TI  - Body weight is modulated by levels of full-length huntingtin.
AB  - Huntington disease is an adult-onset neurodegenerative disorder that is caused by
      the expansion of a polyglutamine tract within the Huntingtin (htt) protein. Wild
      type htt has been shown to be involved in transcription, transport and cell
      survival. Here, we demonstrate that increased expression of full-length wild-type
      htt in mice is associated with a dose-dependent increase in body weight which
      results from an increase in both total fat mass and fat-free mass. Conversely, we
      show that a reduction in the levels of wild-type htt is associated with decreased
      body weight. Examination of individual organ weights revealed that the weight of
      the heart, liver, kidneys, lungs and spleen increased with the over-expression of
      wild-type htt, whereas the brain and testis were unaltered. On the basis of these
      initial findings, we examined mice that over-express full-length mutant htt to
      determine the effect of polyglutamine expansion on this novel function of wild
      type htt. We found that over-expression of full-length mutant htt, but not an N
      terminal fragment of mutant htt, also increased body weight and organ weight,
      except in the brain and testis where mutant htt appears to be toxic. In these
      mice, the majority of weight gain could be accounted for by increases in total
      fat mass. Further investigation of the weight gain phenotype revealed that the
      increases in weight were not accounted for by increased food consumption relative
      to body weight. Overall, we demonstrate that increased levels of both wild-type
      and mutant full-length htt are associated with increased body weight.

PMID- 16571605
TI  - Branching and nucleokinesis defects in migrating interneurons derived from
      doublecortin knockout mice.
AB  - Type I lissencephaly results from mutations in the doublecortin (DCX) and LIS1
      genes. We generated Dcx knockout mice to further understand the
      pathophysiological mechanisms associated with this cortical malformation. Dcx is
      expressed in migrating interneurons in developing human and mouse brains. Video
      microscopy analyses of such tangentially migrating neuron populations derived
      from the medial ganglionic eminence show defects in migratory dynamics.
      Specifically, the formation and division of growth cones, leading to the
      production of new branches, are more frequent in knockout cells, although
      branches are less stable. Dcx-deficient cells thus migrate in a disorganized
      manner, extending and retracting short branches and making less long-distant
      movements of the nucleus. Despite these differences, migratory speeds and
      distances remain similar to wild-type cells. These novel data thus highlight a
      role for Dcx, a microtubule-associated protein enriched at the leading edge in
      the branching and nucleokinesis of migrating interneurons.

PMID- 16571607
TI  - Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high
      regulatory T cell population in peripheral blood.
AB  - OBJECTIVE: Our aim was to test the hypothesis that there is a deficit in the
      CD4+CD25high regulatory T-cell population in early rheumatoid arthritis (RA),
      either in size or functional activity. METHODS: Peripheral blood mononuclear
      cells were examined from subjects with early active RA who had received no
      previous disease-modifying therapy (n = 43), from individuals with self-limiting
      reactive arthritis (n = 14), from subjects with stable, well-controlled RA (n =
      82) and from healthy controls (n = 72). The frequencies of CD4+CD25high T-cells
      were quantified using flow cytometry, and function was assessed by the ability to
      suppress proliferation of CD4+CD25- T-cells. Paired blood and synovial fluid was
      analysed from a small number of RA and reactive arthritis patients. RESULTS:
      There was a smaller proportion of CD4+CD25high T-cells in the peripheral blood of
      early active RA patients (mean 4.25%) than in patients with reactive arthritis or
      in controls (mean 5.90 and 5.30%, respectively, P = 0.001 in each case).
      Frequencies in stable, well-controlled RA (mean 4.63%) were not significantly
      different from early active RA or controls. There were no differences in
      suppressor function between groups. Higher frequencies of CD4+CD25high T-cells
      were found in synovial fluid than blood in both RA and reactive arthritis.
      CONCLUSIONS: These data demonstrate a smaller CD4+CD25high regulatory T-cell
      population in peripheral blood of individuals with early active RA prior to
      disease-modifying treatment. This may be a contributory factor in the
      susceptibility to RA and suggests novel approaches to therapy.

PMID- 16571606
TI  - NF-kappaB is dispensable for normal lymphocyte development in bone marrow but
      required for protection of progenitors from TNFalpha.
AB  - Levels of the nuclear factor-kappa B (NF-kappaB)/Rel family of proteins are
      carefully modulated in differentiating lymphocytes, where these transcription
      factors are thought to be important for survival and fate decisions. In contrast,
      gene-targeting experiments have not revealed clear roles for these transcription
      factors in lymphopoiesis within bone marrow. Inhibition of NF-kappaB by
      introduction of mutated I kappa B alpha, a 'superinhibitor' of NF-kappaB, into
      hematopoietic stem cells or early progenitors suppressed B as well as T
      lymphopoiesis following transplantation into immunodeficient mice. Furthermore, a
      NF-kappaB essential modifier-binding domain (NBD) peptide that blocks IKB kinase
      (IKK) activity selectively impaired the generation of adult B lineage cells.
      However, this suppression did not occur when a neutralizing antibody to tumor
      necrosis factor alpha (TNFalpha) was added to the cultures, or in circumstances
      where few non-lymphoid cells were present. We conclude that while NF-kappaB plays
      a survival-promoting role in lymphoid progenitors, this may only be significant
      in circumstances such as transplantation when levels of TNFalpha are high.

PMID- 16571608
TI  - Adenoviral gene transfer into osteoarthritis synovial cells using the endogenous
      inhibitor IkappaBalpha reveals that most, but not all, inflammatory and
      destructive mediators are NFkappaB dependent.
AB  - OBJECTIVES: Despite recent major advances in the understanding of the
      pathogenesis of rheumatoid arthritis, with tumour necrosis factor-alpha
      (TNFalpha) established as a major therapeutic target, comparatively little is
      known about the mediators involved in the destructive and inflammatory pathways
      in osteoarthritis (OA). Recently, it has become appreciated that an inflammatory
      synovitis contributes not only to the signs and symptoms of osteoarthritis, but
      also to disease progression. Here, we use high-efficiency adenoviral gene
      transfer to investigate the role of the transcription factor nuclear factor
      kappaB (NFkappaB) in regulating inflammatory and destructive mediators in the
      late stage OA synovium. METHODS: Infection with reporter adenoviruses
      transferring the beta-galactosidase or green fluorescent protein genes verified
      that OA synovial cells could be infected (>95%). Adenovirus transferring the
      inhibitory subunit IkappaBalpha inhibited NFkappaB. The production of a whole
      array of pro- and anti-inflammatory cytokines and mediators, and several matrix
      metalloproteinases and their main inhibitor, was measured by enzyme-linked
      immunosorbent assay. RESULTS: The spontaneous production of macrophage-produced
      pro-inflammatory cytokines varied: TNFalpha was modestly inhibited by
      IkappaBalpha overexpression, but interleukin (IL)-1 was unaffected. Both IL-6 and
      IL-8 were potently inhibited, as were granulocyte-macrophage colony stimulating
      factor and oncostatin M. Anti-inflammatory mediators like IL-10, the IL-1
      receptor antagonist and the p55 soluble TNF receptor were unaffected. Matrix
      metalloproteinases 1, 3, 9 and 13 were potently inhibited by IkappaBalpha
      overexpression, but not their main inhibitor tissue inhibitor of
      metalloproteinase-1. CONCLUSIONS: The OA synovium is a highly inflammatory
      environment, with spontaneous production of many cytokines and matrix
      metalloproteinases. Inhibition of NFkappaB may have a beneficial effect on the
      balance between pro-inflammatory cytokines and anti-inflammatory mediators, and
      between destructive metalloproteinases and their main inhibitor.

PMID- 16571610
TI  - Comparison of three auto-adjusting positive pressure devices in patients with
      sleep apnoea.
AB  - Auto-adjustable continuous positive airway pressure (APAP) devices are an
      emerging treatment alternative to fixed-pressure continuous positive airway
      pressure (CPAP) therapy for obstructive sleep apnoea syndrome. They have been
      engineered to automatically adjust the pressure to the optimal level on a
      continuous basis. However, not all APAP technologies use the same algorithm.
      Three different APAP devices (Autoset Spirit, Breas PV 10i and RemStar Auto) were
      compared in a randomised crossover trial in patients already established on fixed
      pressure CPAP therapy. The outcome measures were compliance, quality of life and
      side-effects. Twenty-seven middle-aged patients (25 male) previously diagnosed
      with severe obstructive sleep apnoea syndrome (median (interquartile range)
      apnoea/hypopnoea index 48 (29-76)), established on CPAP therapy for >3 yrs, were
      randomised to each APAP device for 4 weeks. Mean pressure and patient compliance
      were significantly lower on the Breas PV 10i than on the other APAP devices. The
      devices were similar in terms of quality of life, daytime sleepiness and upper
      airway side-effects, but patients evaluated them significantly differently in
      terms of device features, sleep quality and pressure comfort, with the Breas PV
      10i being the least popular. Auto-adjustable positive airway pressure devices
      differ in pressure delivery and patient compliance in obstructive sleep apnoea
      syndrome patients.

PMID- 16571612
TI  - Estimation of the bronchodilatory effect of deep inhalation after a free run in
      children.
AB  - The bronchomotor effects of a deep inhalation (DI) may provide relevant
      information about the mechanisms of exercise-induced airway obstruction in
      children and may be assessed by respiratory conductance (Grs) measured using the
      forced oscillation technique. The aims of the present study were to assess the
      effect of DI on Grs after exercise in relationship to the lung function response
      to exercise. Grs at 12 Hz using a head generator and spirometric data were
      measured in 62 children suspected of asthma before and 5 min after a 6-min free
      run. After exercise, Grs was significantly increased by DI in 38 subjects, who
      also showed larger Grs and forced expiratory volume in one second (FEV1)/forced
      vital capacity (FVC) responses to exercise than the 24 nonresponders. Stepwise
      regression indicated significant correlation between the response of Grs to DI
      and both Grs and FEV1/FVC responses to exercise. The data are consistent with
      exercise-induced bronchoconstriction being reversed by deep inhalation.

PMID- 16571611
TI  - Ventilation inhomogeneity in alpha1-antitrypsin-deficient emphysema.
AB  - The slope of phase III of the single-breath nitrogen wash-out test (sbN2-test)
      measures ventilation inhomogeneity and, in smokers, is strongly associated with
      small airways pathology. The present authors aimed to study ventilation
      inhomogeneity in emphysema related to type Z alpha1-antitrypsin (AAT) and to
      assess its relationship with indices of parenchymal damage and airways
      obstruction. A total of 18 subjects, consisting of ex-smokers with type Z AAT and
      emphysema (confirmed by computed tomography scan), were studied in a cross
      sectional design. Post-bronchodilation flow-volume curves and gas transfer
      parameters were measured; sbN2-test curves were obtained and the slope of phase
      III was determined. The mean value of the slope (4.6+/-1.3% N2 x L(-1)) was
      higher than reference values +2sd; it was significantly correlated with the
      transfer factor of the lung for carbon monoxide (R = -0.75) and the transfer
      coefficient of the lung for carbon monoxide (R = -0.58), but not with airways
      obstruction. There was no correlation between phase III slope values and
      cumulative smoking. In patients with type Z alpha1-antitrypsin emphysema, the
      increased ventilation inhomogeneity predominantly reflects parenchymal
      abnormalities, demonstrating that measurement of airways obstruction is not
      sufficient to characterise the disease. Determination of the sensitivity of the
      single-breath nitrogen wash-out test slope in detecting disease progression may
      give complementary information to spirometry.

PMID- 16571613
TI  - Allergic lung inflammation induces pulmonary vascular hyperresponsiveness.
AB  - Pulmonary arterial vasoconstriction is an important early component of pulmonary
      hypertension. Inflammatory mechanisms play a prominent role in the pathogenesis
      of pulmonary hypertension. The present authors investigated the potential role of
      acute allergic lung inflammation for alterations in pulmonary haemodynamics.
      BALB/c mice were intraperitoneally sensitised to ovalbumin and challenged by
      ovalbumin inhalation. Subsequently, lungs were ventilated and perfused ex vivo,
      and pulmonary arterial pressure (P(pa)) was continuously monitored. Isolated
      perfused lungs of allergen-sensitised and -challenged mice showed five-fold
      enhanced P(pa) responses to serotonin, which is reported to be a significant
      contributor to pulmonary hypertension in humans. This increase in P(pa) was
      abolished by the serotonin receptor-2A antagonist ketanserin, but not the
      serotonin receptor-1B antagonist GR127935. Intracellular signalling to serotonin
      involved phosphatidylcholine-specific phospholipase C and protein kinase C, as
      well as Rho-kinase, as assessed by employing the specific inhibitors D609,
      bisindolylmaleimide and Y27632, respectively. In addition to serotonin,
      impressively enhanced P(pa) increases in allergic lungs were also evoked by the
      thromboxane receptor agonist U46619, angiotensin II and endothelin-1. In
      conclusion, allergic lung inflammation was accompanied by impressive pulmonary
      vascular hyperresponsiveness. These results suggest a possible role for allergic
      inflammation in the development of pulmonary arterial hypertension.

PMID- 16571614
TI  - Lymphoid interstitial pneumonia: clinical features, associations and prognosis.
AB  - Lymphoid interstitial pneumonia (LIP) is rare and its clinical course
      incompletely described. The aim of this study was to examine the clinical
      features, associations and prognosis of surgical lung biopsy-proven LIP. The
      study group consisted of 15 subjects encountered over a 14-yr period. The
      majority of subjects were females (n = 11) and the mean age was 47 yrs (range 17
      78 yrs). Underlying systemic immune disorders were frequent, including Sjogren's
      syndrome (n = 8), rheumatoid arthritis, systemic lupus erythematosus,
      polymyositis, common variable immunodeficiency and dysproteinaemia. Only three
      patients were classified as "idiopathic". Presenting symptoms were dominated by
      dyspnoea and cough. Restrictive physiology, reduced diffusion capacity (62.5+/
      18.4% predicted) and bronchoalveolar lavage lymphocytosis (30.5+/-29.1% pred)
      were noted. Thirteen patients received corticosteroid therapy. Of the nine whose
      response could be assessed, four showed clinical improvement and four were
      stable. Overall, median survival was 11.5 yrs. Of the seven patients who died,
      respiratory problems were the primary cause of death in three. Conversion to
      lymphoma was not identified. In conclusion, histopathological lymphoid
      interstitial pneumonia is commonly associated with immune system dysregulation,
      with idiopathic lymphoid interstitial pneumonia being extremely rare. Clinical
      stability or improvement with corticosteroids can be expected; however, survival
      remains impaired.

PMID- 16571615
TI  - Cost-optimisation of screening for latent tuberculosis in close contacts.
AB  - The aim of the present study was to perform cost-minimisation analysis of contact
      investigation from a public health perspective using the tuberculin skin test
      (TST) and a new blood assay, QuantiFERON-TB Gold (QFT-G). A decision-analysis
      model simulated the costs of investigating a cohort of adult close tuberculosis
      contacts by the public health service following the current German guidelines
      over a period of 2 yrs. The economic outcomes were compared with alternative
      screening strategies. These were: 1) QFT-G instead of TST; 2) TST followed by QFT
      G; and 3) TST followed by QFT-G in vaccinated (bacille Calmette-Guerin (BCG))
      subjects. In a base-case analysis, the costs of TST-based screening were 91.06
      Euros (EUR).contact(-1), assuming a 1% tuberculosis-case-finding incidence. The
      least expensive strategy was TST screening plus subsequent QFT-G testing (52.05
      EUR), resulting in a 43% cost reduction. Using QFT-G alone in BCG-vaccinated
      subjects who tested positive in the TST led to a 39% cost reduction. The savings
      using QFT-G alone instead of TST amounted to 29.77 EUR.contact(-1). The results
      depended on the acquisition costs assumed and the proportion of positive results
      in TST-based screening. Screening for tuberculosis by combining tuberculin skin
      testing and QuantiFERON-TB Gold markedly reduces public health costs compared
      with tuberculin skin test screening alone.

PMID- 16571616
TI  - Alexithymia: a relevant psychological variable in near-fatal asthma.
AB  - Alexithymia is a psychological trait characterised by difficulty in perceiving
      and expressing emotions and body sensations. Failure to perceive dyspnoea could
      lead alexithymic asthmatics to underestimate the severity of an asthma
      exacerbation, and thereby increase the risk of developing a fatal or near-fatal
      asthma (NFA) attack. The objective of the present study was to determine the
      prevalence of alexithymia in NFA patients and to analyse their clinical
      characteristics. Alexithymia was assessed using the Toronto Alexithymia Scale in
      this multicentric prospective observational study. From 33 Spanish hospitals, 179
      NFA patients and 40 non-NFA patients, as a control group, were enrolled. There
      was a higher proportion of alexithymia in the NFA group than in the non-NFA group
      (36 versus 13%). Patients with NFA and alexithymia were older than the rest of
      the NFA group, and had a lower level of education, a higher level of psychiatric
      morbidity, a higher proportion of severe persistent asthma and a greater number
      of prior very severe asthma exacerbations (49 versus 27%). Alexithymia, severe
      persistent asthma and a low level of education were identified as independent
      variables related to repeated very severe asthma exacerbations. The results show
      that alexithymia is more frequent in near-fatal asthma patients compared to the
      rest of asthmatics and is associated with recurrent very severe asthma
      exacerbations.

PMID- 16571617
TI  - The bulk elastic modulus and the reversible properties of cell walls in
      developing Quercus leaves.
AB  - We examined the relationship between the bulk elastic modulus (epsilon) of an
      individual leaf obtained by the pressure-volume (P-V) technique and the
      mechanical properties of cell walls in the leaf. The plants used were Quercus
      glauca and Q. serrata, an evergreen and a deciduous broad-leaved tree species,
      respectively. We compared epsilon and Young's modulus of leaf specimens
      determined by the stretch technique at various stages of their leaf development.
      The results showed that epsilon increased from approximately 5 to 20 MPa during
      leaf development, although other potential determinants of epsilon such as the
      apoplastic water content in the leaf and the diameter of a palisade tissue cells
      remained almost constant. epsilon in these two species was similar at every
      developmental stages, although the apparent mechanical strength of the leaf
      lamina and thickness of mesophyll cell walls were greater in Q. glauca. There
      were significant linear relationships between Young's modulus and epsilon (P <
      0.01; R (2) = 0.78 and 0.84 in Q. glauca and Q. serrata, respectively) with small
      y-intercepts. From these results, we conclude that epsilon is closely related to
      the reversible properties of the cell walls. From the estimation of epsilon based
      on a physical model, we suggest that the effective thickness of cell walls
      responsible for epsilon is smaller than the observed wall thickness.

PMID- 16571618
TI  - Expressed sequence tag analysis of Lilium longiflorum generative cells.
AB  - The generative cell, the male gametic cell progenitor in flowering plants,
      undergoes mitotic division to produce two sperm cells. We have examined the gene
      expression profile of the Lilium longiflorum (lily) generative cell by sequencing
      expressed sequence tags (ESTs). A total of 886 ESTs derived from the generative
      cell cDNA library were clustered into 637 unique ESTs comprising 123 cluster ESTs
      and 514 singleton ESTs. Thirty-nine percent of non-redundant ESTs showing
      similarity to Arabidopsis genes with known function were thus assigned putative
      functions. Genes related to the ubiquitin system were abundant, suggesting the
      key role of ubiquitin-dependent proteolysis in gametogenesis. A total of 168 and
      129 non-redundant lily generative cell ESTs showed significant similarity to
      maize sperm cell ESTs and Arabidopsis male gametophyte-specific transcripts,
      respectively. Fifty-five ESTs appeared to have significant similarities to both
      maize sperm cell ESTs and Arabidopsis male gametophyte-specific genes, indicating
      conservation of male gamete-expressed genes across different plant genera. Thus
      our data provide a handle to identify Arabidopsis gamete-expressed genes and to
      investigate their function. Several of these genes are potential candidates for
      analyzing the molecular basis of fertilization and for investigating mechanisms
      of gamete-specific transcriptional regulation in Arabidopsis through
      bioinformatics-based approaches.

PMID- 16571619
TI  - Chronic ethanol consumption decreases mitochondrial and glycolytic production of
      ATP in liver.
AB  - AIMS: The synthesis of ATP in the liver of the chronic ethanol consumer is
      suppressed, particularly if the tissue becomes hypoxic. Moreover, the perivenous
      region of the liver lobule becomes even more oxygen deficient as a result of
      ethanol consumption. Synthesis of ATP in the perivenous region of the lobule may
      be depressed in the chronic ethanol consumer due to decreases in both
      mitochondrial and glycolytic activities. In this study the effects of hypoxia on
      hepatic ATP levels derived from synthesis by both oxidative phosphorylation and
      the glycolytic mechanisms were investigated. METHODS: Rats were pair-fed liquid
      diets containing 36% of calories as ethanol or an isocaloric control diet. The
      contributions of glycolysis and mitochondria to ATP production were assessed
      employing oligomycin, an inhibitor of oxidative phosphorylation. In order to
      localize the ethanol-elicited lesion in the glycolytic pathway, the metabolism of
      [3-(3)H] D-glucose was followed in hepatocytes from ethanol-fed and control
      animals. RESULTS: Under both hypoxic and normoxic conditions ATP losses were due
      to decreases in both glycolytic and mitochondrial ATP production. The rate of
      production of tritiated water from [3-(3)H] D-glucose was significantly decreased
      in hepatocytes from ethanol-fed animals, which indicates there is an ethanol
      elicited lesion in glycolysis between glucose and glyceraldehyde-3-phosphate.

PMID- 16571620
TI  - Do community factors have a differential impact on the health outcomes of boys
      and girls? Evidence from rural Pakistan.
AB  - In countries with large gender disparities in health status, can investments in
      local communities mitigate the gender bias observed in intra-household resource
      allocations? This paper explores the evidence for gender differences in the
      impact of community prices and infrastructure on child nutritional outcomes.
      Standardized heights and weights of rural Pakistani children are used as health
      indicators, while community factors include wheat prices, availability of piped
      water, accessibility of shops and government health clinics and the quality of
      the closest health facilities. The results suggest that food subsidies and
      programmes designed to improve the access and quality of local services may
      reduce the impact of intra-household gender bias on child nutrition, particularly
      in the long run. Specifically, by increasing the affordability of staple foods,
      improving the access to shops and government health centres and enhancing the
      quality of local care, particularly (gender-neutral) prenatal care, gender gaps
      in health outcomes are likely to diminish.

PMID- 16571621
TI  - Surface reactivity, cytotoxic, and morphological transforming effects of
      diatomaceous Earth products in Syrian hamster embryo cells.
AB  - In order to evaluate the effect of thermal treatments on the surface reactivity
      and carcinogenic potential of diatomaceous earth (DE) products, the
      physicochemical features of some specimens--derived by heating the same original
      material--were compared with their cytotoxic and transforming potency. The
      samples were an untreated DE (amorphous) progressively heated in the laboratory
      at 900 degrees C (DE 900) and 1200 degrees C (DE 1200) and a commercial product
      manufactured from the same DE (Chd) from which the finer fraction (< 10-microm
      diameter) was separated (Chd-F). Quartz (Min-U-Sil 5) and a vitreous silica
      (amorphous) smoothed up with hydrofluoric acid and were used as positive and
      negative controls, respectively. All samples were analyzed for their degree of
      crystallization, for their ability to release free radicals and reactive oxygen
      species, and for their cytotoxic and transforming potencies in Syrian hamster
      embryo (SHE) cells. X-ray diffractometry showed that DE 900, like DE, was still
      amorphous, whereas DE 1200 as well as the commercial product (Chd) were partially
      crystallized into cristobalite. The ability of the dust to release hydroxyl (*OH)
      radicals in the presence of hydrogen peroxide, as revealed by the spin-trapping
      technique, was as follows: Chd-F, DE 1200 > Chd > DE 900 > DE, suggesting that on
      heating, the surface acquires a higher potential for free radical release. Most
      of the silica samples generated COO* radicals from the formate ion, following
      homolytic rupture of the carbon-hydrogen bond, in the presence of ascorbic acid.
      A concentration-dependent decrease in cell proliferation and colony-forming
      efficiency was observed in SHE cultures treated with Chd-F, Chd, and DE. Heating
      abolished DE cytotoxicity but conferred a transforming ability to thermal treated
      particles. DE was the only sample that did not induce morphological
      transformation of cells. According to their transformation capacity, the samples
      were classified as follows: Chd-F > Chd, DE 1200 > DE 900 >> DE. Taken together,
      the reported results suggest that (1) the transforming potential of a biogenic
      amorphous silica is related to the thermal treatment that transforms the original
      structure in cristobalite and generates surface active sites; (2) the reactivity
      of samples in releasing *OH radicals correlates to their transforming ability;
      (3) the finer fraction of the commercial product is significantly more toxic and
      transforming than the coarse dust; and (4) opposite to silica dusts of mineral
      origin, which loose both cytotoxicity and transforming ability upon heating,
      heated diatomite acquires a cell-transforming potency. DE products should be thus
      considered a set apart of silica-based potentially toxic materials.

PMID- 16571622
TI  - CCNs, fibulin-1C and S100A4 expression in leiomyoma and myometrium: inverse
      association with TGF-beta and regulation by TGF-beta in leiomyoma and myometrial
      smooth muscle cells.
AB  - Connective tissue growth factor (CTGF; CCN2) is considered to serve as downstream
      midiator of TGF-beta action in tissue fibrosis. We tested this hypothesis in
      paired leiomyoma and myometrium by evaluating the expression of TGF-beta1/TGF
      beta3 and CCN2, the other members of the CCN family, CCN3 and CCN4, as well as
      fibulin-1C and S100A4, calcium-binding proteins that interact with CCNs. The
      regulatory function of TGF-beta1 on the expression of these genes was further
      evaluated using leiomyoma (L) and myometrial (M) smooth muscle cells (SMC). Real
      time PCR, Western blotting and immunohistochemistry revealed that leiomyomas and
      myometrium express CCNs, fibulin-1C and S100A4, whose levels of expression with
      the exception of fibulin-1C were lower in leiomyomas and inversely correlated
      with the expression of TGF-beta1 and TGF-beta3 (P<0.05). The expression of these
      genes was menstrual cycle-independent and GnRHa therapy increased the expression
      of CCN2 in leiomyomas, while inhibiting CCN3, CCN4 and S100A4 in myometrium
      (P<0.05). TGF-beta (2.5 ng/ml) in a time- and cell-dependent manner, and through
      MAPK and Smad pathways, differentially regulated the expression of these genes in
      LSMC and MSMC. We concluded that CCNs, fibulin-1C and S100A4 are expressed in
      leiomyomas/myometrium with relative expression levels inversely correlating with
      TGF-betas and influenced by GnRHa and TGF-beta regulatory actions. The results
      suggest that unlike other fibrotic disorders, CCN2 (CTGF), at least at tissue
      level, may not serve as a downstream mediator of TGF-beta action in leiomyomas.

PMID- 16571623
TI  - Relative reinforcing effects of cocaine, remifentanil, and their combination in
      rhesus monkeys.
AB  - Human polydrug abusers often take combinations of opioids and stimulants, but it
      is not clear why. Behavioral economics with demand curve analysis is uniquely
      able to separate two of the possibilities: that the drug combination increases
      the reinforcing potency of the component drugs or that the drug combination is a
      more effective reinforcer than either drug alone. Rhesus monkeys self
      administered a range of doses of cocaine, remifentanil, and combinations of the
      drugs through indwelling intravenous catheters; the number of responses required
      for each drug infusion increased across drug-availability sessions. Combining
      small doses of cocaine and remifentanil that by themselves resulted in very low
      rates of responding yielded rates of responding that were higher than the maximum
      maintained by any dose of the constituent drugs. Nevertheless, demand curve
      analysis demonstrated that the drug combination was equally elastic as the
      component drugs, indicating that it was not more effective as a reinforcer than
      either cocaine or remifentanil alone. This suggests that enhanced self
      administration of this particular drug combination is due primarily to the drug
      enhancement of the potency of the other drug.

PMID- 16571624
TI  - Wnt signaling establishes anteroposterior neuronal polarity and requires retromer
      in C. elegans.
AB  - Secreted Wnt proteins influence neural connectivity by regulating axon guidance,
      dendritic morphogenesis and synapse formation. We report a new role for Wnt and
      Frizzled proteins in establishing the anteroposterior polarity of the
      mechanosensory neurons ALM and PLM in C. elegans. Disruption of Wnt signaling
      leads to a complete inversion of ALM and PLM polarity: the anterior process
      adopts the length, branching pattern and synaptic properties of the wild-type
      posterior process, and vice versa. Different but overlapping sets of Wnt proteins
      regulate neuronal polarity in different body regions. Wnts act directly on PLM
      via the Frizzled LIN-17. In addition, we show that they are needed for axon
      branching and anteriorly directed axon growth. We also find that the retromer, a
      conserved protein complex that mediates transcytosis and endosome-to-Golgi
      protein trafficking, plays a key role in Wnt signaling. Deletion mutations of
      retromer subunits cause ALM and PLM polarity, and other Wnt-related defects. We
      show that retromer protein VPS-35 is required in Wnt-expressing cells and propose
      that retromer activity is needed to generate a fully active Wnt signal.

PMID- 16571625
TI  - The level of sonic hedgehog signaling regulates the complexity of cerebellar
      foliation.
AB  - Foliation of the mouse cerebellum occurs primarily during the first 2 weeks after
      birth and is accompanied by tremendous proliferation of granule cell precursors
      (GCPs). We have previously shown that sonic hedgehog (Shh) signaling correlates
      spatially and temporally with fissure formation, and that Gli2 is the main
      activator driving Shh induced proliferation of embryonic GCPs. Here, we have
      tested whether the level of Shh signaling regulates the extent of cerebellar
      foliation. By progressively lowering signaling by removing Gli1 and Gli2 or the
      Shh receptor smoothened, we found the extent of foliation is gradually reduced,
      and that this correlates with a decrease in the duration of GCP proliferation.
      Importantly, the pattern of the remaining fissures in the mutants corresponds to
      the first fissures that form during normal development. In a complementary
      manner, an increase in the level and length of Shh signaling results in formation
      of an extra fissure in a position conserved in rat. The complexity of cerebellar
      foliation varies greatly between vertebrate species. Our studies have uncovered a
      mechanism by which the level and length of Shh signaling could be integral to
      determining the distinct number of fissures in each species.

PMID- 16571626
TI  - p90Rsk is required for G1 phase arrest in unfertilized starfish eggs.
AB  - The cell cycle in oocytes generally arrests at a particular meiotic stage to
      await fertilization. This arrest occurs at metaphase of meiosis II (meta-II) in
      frog and mouse, and at G1 phase after completion of meiosis II in starfish.
      Despite this difference in the arrest phase, both arrests depend on the same Mos
      MAPK (mitogen-activated protein kinase) pathway, indicating that the difference
      relies on particular downstream effectors. Immediately downstream of MAPK, Rsk
      (p90 ribosomal S6 kinase, p90(Rsk)) is required for the frog meta-II arrest.
      However, the mouse meta-II arrest challenges this requirement, and no downstream
      effector has been identified in the starfish G1 arrest. To investigate the
      downstream effector of MAPK in the starfish G1 arrest, we used a neutralizing
      antibody against Rsk and a constitutively active form of Rsk. Rsk was activated
      downstream of the Mos-MAPK pathway during meiosis. In G1 eggs, inhibition of Rsk
      activity released the arrest and initiated DNA replication without fertilization.
      Conversely, maintenance of Rsk activity prevented DNA replication following
      fertilization. In early embryos, injection of Mos activated the MAPK-Rsk pathway,
      resulting in G1 arrest. Moreover, inhibition of Rsk activity during meiosis I led
      to parthenogenetic activation without meiosis II. We conclude that immediately
      downstream of MAPK, Rsk is necessary and sufficient for the starfish G1 arrest.
      Although CSF (cytostatic factor) was originally defined for meta-II arrest in
      frog eggs, we propose to distinguish ;G1-CSF' for starfish from ;meta-II-CSF' for
      frog and mouse. The present study thus reveals a novel role of Rsk for G1-CSF.

PMID- 16571628
TI  - Lack of beta1 integrins in enteric neural crest cells leads to a Hirschsprung
      like phenotype.
AB  - The enteric nervous system arises mainly from vagal and sacral neural crest cells
      that colonise the gut between 9.5 and 14 days of development in mice. Using the
      Cre-LoxP system, we removed beta1 integrins in the neural crest cells when they
      emerge from the neural tube. beta1-null enteric neural crest cells fail to
      colonise the gut completely, leading to an aganglionosis of the descending colon,
      which resembles the human Hirschsprung's disease. Moreover, beta1-null enteric
      neural crest cells form abnormal aggregates in the gut wall, leading to a severe
      alteration of the ganglia network organisation. Organotypic cultures of gut
      explants reveal that beta1-null enteric neural crest cells show impaired adhesion
      on extracellular matrix and enhanced intercellular adhesion properties. They
      display migration defects in collagen gels and gut tissue environments. We also
      provide evidence that beta1 integrins are required for the villi innervation in
      the small intestine. Our findings highlight the crucial roles played by beta1
      integrins at various steps of enteric nervous system development.

PMID- 16571629
TI  - XNF-ATc3 affects neural convergent extension.
AB  - Convergent extension is the primary driving force elongating the anteroposterior
      body axis. In Xenopus, convergent extension occurs in the dorsal mesoderm and
      posterior neural ectoderm, and is mediated by similar molecular pathways within
      these tissues. In this paper, we show that activation of NF-AT, a transcription
      factor known to modulate multiple signaling events, inhibits convergent extension
      in the dorsal mesoderm and in the posterior neural ectoderm. This is seen in
      whole embryos, mesodermal explants and posterior neural explants, solidly
      implicating a role of NF-AT in convergent extension. In the whole embryo,
      inhibition of NF-AT reveals a more selective function, affecting only convergent
      extension in the neural ectoderm. This specific activity was further teased apart
      using a variety of temporal and spatial approaches. Targeted injections of
      dominant-negative XNF-ATc3, or dosing over time with the calcineurin inhibitor
      cyclosporin in neural tube explants or in whole embryos, shows that inhibition of
      NF-AT signaling blocks neural convergent extension. Consistent with a function in
      neural convergent extension, we show that XNF-ATc3 is expressed and
      transcriptionally active within the neural tube. This work identifies XNF-ATc3 as
      a regulator of neural convergent extension in Xenopus and adds to a short list of
      molecules involved in this process.

PMID- 16571627
TI  - Dishevelled genes mediate a conserved mammalian PCP pathway to regulate
      convergent extension during neurulation.
AB  - The planar cell polarity (PCP) pathway is conserved throughout evolution, but it
      mediates distinct developmental processes. In Drosophila, members of the PCP
      pathway localize in a polarized fashion to specify the cellular polarity within
      the plane of the epithelium, perpendicular to the apicobasal axis of the cell. In
      Xenopus and zebrafish, several homologs of the components of the fly PCP pathway
      control convergent extension. We have shown previously that mammalian PCP
      homologs regulate both cell polarity and polarized extension in the cochlea in
      the mouse. Here we show, using mice with null mutations in two mammalian
      Dishevelled homologs, Dvl1 and Dvl2, that during neurulation a homologous
      mammalian PCP pathway regulates concomitant lengthening and narrowing of the
      neural plate, a morphogenetic process defined as convergent extension. Dvl2
      genetically interacts with Loop-tail, a point mutation in the mammalian PCP gene
      Vangl2, during neurulation. By generating Dvl2 BAC (bacterial artificial
      chromosome) transgenes and introducing different domain deletions and a point
      mutation identical to the dsh1 allele in fly, we further demonstrated a high
      degree of conservation between Dvl function in mammalian convergent extension and
      the PCP pathway in fly. In the neuroepithelium of neurulating embryos, Dvl2 shows
      DEP domain-dependent membrane localization, a pre-requisite for its involvement
      in convergent extension. Intriguing, the Loop-tail mutation that disrupts both
      convergent extension in the neuroepithelium and PCP in the cochlea does not
      disrupt Dvl2 membrane distribution in the neuroepithelium, in contrast to its
      drastic effect on Dvl2 localization in the cochlea. These results are discussed
      in light of recent models on PCP and convergent extension.

PMID- 16571630
TI  - Sonic hedgehog regulates Gli activator and repressor functions with spatial and
      temporal precision in the mid/hindbrain region.
AB  - The midbrain and anterior hindbrain offer an ideal system in which to study the
      coordination of tissue growth and patterning in three dimensions. Two organizers
      that control anteroposterior (AP) and dorsoventral (DV) development are known,
      and the regulation of AP patterning by Fgf8 has been studied in detail. Much less
      is known about the mechanisms that control mid/hindbrain development along the DV
      axis. Using a conditional mutagenesis approach, we have determined how the
      ventrally expressed morphogen sonic hedgehog (Shh) directs mid/hindbrain
      development over time and space through positive regulation of the Gli activators
      (GliA) and inhibition of the Gli3 repressor (Gli3R). We have discovered that
      Gli2A-mediated Shh signaling sequentially induces ventral neurons along the
      medial to lateral axis, and only before midgestation. Unlike in the spinal cord,
      Shh signaling plays a major role in patterning of dorsal structures (tectum and
      cerebellum). This function of Shh signaling involves inhibition of Gli3R and
      continues after midgestation. Gli3R levels also regulate overall growth of the
      mid/hindbrain region, and this largely involves the suppression of cell death.
      Furthermore, inhibition of Gli3R by Shh signaling is required to sustain
      expression of the AP organizer gene Fgf8. Thus, the precise spatial and temporal
      regulation of Gli2A and Gli3R by Shh is instrumental in coordinating
      mid/hindbrain development in three dimensions.

PMID- 16571631
TI  - Inactivation of aPKClambda results in the loss of adherens junctions in
      neuroepithelial cells without affecting neurogenesis in mouse neocortex.
AB  - In developing mammalian telencephalon, the loss of adherens junctions and cell
      cycle exit represent crucial steps in the differentiation of neuroepithelial
      cells into neurons, but the relationship between these cellular events remains
      obscure. Atypical protein kinase C (aPKC) is known to contribute to junction
      formation in epithelial cells and to cell fate determination for Drosophila
      neuroblasts. To elucidate the functions of aPKClambda, one out of two aPKC
      members, in mouse neocortical neurogenesis, a Nestin-Cre mediated conditional
      gene targeting system was employed. In conditional aPKClambda knockout mice,
      neuroepithelial cells of the neocortical region lost aPKClambda protein at
      embryonic day 15 and demonstrated a loss of adherens junctions, retraction of
      apical processes and impaired interkinetic nuclear migration that resulted in
      disordered neuroepithelial tissue architecture. These results are evidence that
      aPKClambda is indispensable for the maintenance of adherens junctions and may
      function in the regulation of adherens junction integrity upon differentiation of
      neuroepithelial cells into neurons. In spite of the loss of adherens junctions in
      the neuroepithelium of conditional aPKClambda knockout mice, neurons were
      produced at a normal rate. Therefore, we concluded that, at least in the later
      stages of neurogenesis, regulation of cell cycle exit is independent of adherens
      junctions.

PMID- 16571632
TI  - Regulation of Dictyostelium prestalk-specific gene expression by a SHAQKY family
      MYB transcription factor.
AB  - PstA and pstO cells are the two major populations in the prestalk region of the
      Dictyostelium slug and DIF-1 is a low molecular weight signalling molecule that
      selectively induces pstO cell-specific gene expression. The two cell types are
      defined by their differential use of spatially separated regions of the ecmA
      promoter. Additionally, there are anterior-like cells (ALCs) scattered throughout
      the rear, prespore region of the slug. They, like the pstO cells, use a cap-site
      distal ecmA promoter segment termed the ecmO region. When multimerised, a 22
      nucleotide subsegment of the ecmO region directs expression in pstA cells, pstO
      cells and ALCs. It also directs DIF-inducible gene expression. The 22-nucleotide
      region was used to purify MybE, a protein with a single MYB DNA-binding domain of
      a type previously found only in a large family of plant transcription factors.
      Slugs of a mybE-null (mybE-) strain express an ecmAO:lacZ fusion gene (i.e. a
      reporter construct containing the ecmA and ecmO promoter regions) in pstA cells
      but there is little or no expression in pstO cells and ALCs. The ecmA gene is not
      induced by DIF-1 in a mybE-strain. Thus, MybE is necessary for DIF-1
      responsiveness and for the correct differentiation of pstO cells and ALCs.

PMID- 16571633
TI  - Sp8 controls the anteroposterior patterning at the midbrain-hindbrain border.
AB  - The specification of neuronal cell types in the developing neural tube is
      orchestrated by signaling centers. However, how patterned territories of the
      central nervous system (CNS) are organized into structures with appropriate size
      and shape is still unclear. We report that in the absence of the mouse
      transcription factor mBtd/Sp8, a posterior shift of the isthmic organizer (IsO)
      occurs, suggesting a crucial role for Sp8 in this process. In addition, large
      patches of cells ectopically expressing Fgf8, Otx2 and/or Wnt1 in the rostral
      hindbrain are detected in Sp8 mutant embryos. In this context, midbrain
      dopaminergic neurons are found posterior to the IsO. Furthermore, we provide
      evidence that cell proliferation in the mid- and hindbrain is tightly controlled
      by Sp8 activity. Our observations are consistent with a role for Sp8 in
      restricting Fgf8 expression at the IsO.

PMID- 16571634
TI  - Twinstar, the Drosophila homolog of cofilin/ADF, is required for planar cell
      polarity patterning.
AB  - Planar cell polarity (PCP) is a level of tissue organization in which cells adopt
      a uniform orientation within the plane of an epithelium. The process of tissue
      polarization is likely to be initiated by an extracellular gradient. Thus,
      determining how cells decode and convert this graded information into subcellular
      asymmetries is key to determining how cells direct the reorganization of the
      cytoskeleton to produce uniformly oriented structures. Twinstar (Tsr), the
      Drosophila homolog of Cofilin/ADF (actin depolymerization factor), is a component
      of the cytoskeleton that regulates actin dynamics. We show here that various
      alleles of tsr produce PCP defects in the wing, eye and several other epithelia.
      In wings mutant for tsr, Frizzled (Fz) and Flamingo (Fmi) proteins do not
      properly localize to the proximodistal boundaries of cells. The correct
      asymmetric localization of these proteins instructs the actin cytoskeleton to
      produce one actin-rich wing hair at the distal-most vertex of each cell. These
      results argue that actin remodeling is not only required in the manufacture of
      wing hairs, but also in the PCP read-out that directs where a wing hair will be
      secreted.

PMID- 16571635
TI  - Transjugular intrahepatic portosystemic stent shunt (TIPSS) modification in the
      management of post-TIPSS refractory hepatic encephalopathy.
AB  - BACKGROUND: Post-transjugular intrahepatic portosystemic stent shunt (TIPSS)
      hepatic encephalopathy (HE) can occur in up to one third of patients. In 5%, this
      can be refractory to optimal medical treatment and may require shunt
      modification. The efficacy of shunt modification has been poorly studied. AIMS:
      To evaluate the efficacy of and natural history following TIPSS modification for
      treatment of refractory HE. METHODS: From a dedicated database, we selected and
      further studied patients who had TIPSS modification for refractory HE. RESULTS:
      Over a 14 year period, of 733 TIPSS insertions, 211(29%) patients developed HE
      post-TIPSS. In 38 patients, shunt modification (reduction (n = 9) and occlusion
      (n = 29)) was performed for refractory HE. Indications for TIPSS were: variceal
      bleeding (n = 32), refractory ascites (n = 5), and other (n = 1). Child's grades
      A, B, and C were noted in 11%, 47%, and 42% of cases, respectively. HE improved
      in 58% of patients and remained unchanged or worsened in 42%, with similar
      results for occlusions and reductions. Following shunt modification, variceal
      bleeding recurred in three patients and ascites in three. Twenty five patients
      have died (liver related in 15) at a median duration of 10.2 months. Three
      patients died due to procedure related complications following shunt occlusions
      (mesenteric infarction (n = 2) and septicaemia (n = 1)). Median survival of
      patients whose HE did not improve following shunt modification was 79 days
      compared with 278 days in patients whose did (p<0.05). No variables independently
      predicted response to shunt modification. CONCLUSIONS: TIPSS modification is a
      useful option for patients with refractory HE following TIPSS insertion. Due to
      the significant risk of iatrogenic complications with shunt occlusions, shunt
      reduction is a safer and preferred option.

PMID- 16571637
TI  - Determination of genotoxicity of classical swine fever vaccine in vitro by
      cytogenetic and comet tests.
AB  - Chromosome damage in lymphocyte cultures induced by live virus vaccine against
      classical swine fever (CSF) has been observed in previous studies. In vivo
      cytogenetic tests were made with several doses of vaccines used in Argentina to
      control the disease. These studies have shown that genotoxic effects increased
      with dose. In the present study, two different in vitro assays were performed by
      recording the frequency of cells with chromosome alterations and by assessing the
      ability of the vaccine to damage DNA, using the single cell gel
      microelectrophoretic assay (comet test). Frequencies of cells with chromosomal
      alterations increased significantly when compared with controls and were dose
      (microl/ml) dependent: 0 = 1.23, 5 = 2.29, 10 = 5.42 and 20 = 11.71%. In the
      comet assay the variables measured, tail length (TL) and tail moment (TM), also
      increased. For control cultures TL was 2.32 microm, whereas with concentrations
      of 20 and 100 microl/ml TL were 12.47 and 42.3 microm, respectively. TM of
      control cultures was 0.18, whereas with vaccine concentrations of 20 and 100
      microl/ml TM were 5.52 and 24.52, respectively. Comet frequency distributions
      differed significantly among treatments. These results agree with previous in
      vivo observations. Regarding CSF pathogeny, our results support a direct effect
      of CSF vaccinal virus on lymphocyte DNA. Genotoxicity of CSF vaccine was
      corroborated in vitro at the cytogenetic and molecular levels.

PMID- 16571639
TI  - Embryo research: is disclosing commercial intent enough?
AB  - This article critically reviews legislative and ethical frameworks that regulate
      embryo research. Australian legislation for embryo research is currently being
      reviewed. It is a legal mandate that scientists disclose to embryo donors any
      intent to pursue commercial gain from altruistic donation. But scientists are
      also required to inform donors that, as donors, they too must not benefit
      financially. In the same political context, public subsidy for IVF treatment is
      under review. There is contradiction in values and indication of inequity in the
      Australian social context. IVF is undervalued, yet products derived from IVF
      embryos are imbued with public hope. Rather than regulate to balance this
      inequity, assumptions of altruism and attention to autonomy in legislative
      framework give it further scope. This article proposes that justice be addressed
      by acknowledging reproductive effort, and thereby embryo research be considered
      in terms of reciprocity. It further proposes regulation of commercial profit and
      the imposition of a redirected tax levy.

PMID- 16571636
TI  - Endomysial antibody-negative coeliac disease: clinical characteristics and
      intestinal autoantibody deposits.
AB  - BACKGROUND: Some patients with untreated coeliac disease are negative for serum
      endomysial autoantibodies (EmA) targeted against transglutaminase 2 (TG2). AIMS:
      To evaluate the clinical and histological features of EmA-negative coeliac
      disease, and to examine whether EmA-equivalent autoantibodies against TG2 can be
      seen in the small-bowel mucosa when absent in serum. PATIENTS: Serum EmA was
      studied in 177 biopsy-proved specimens from adult patients with coeliac disease.
      20 patients with intestinal diseases served as non-coeliac controls; three had
      autoimmune enteropathy with villous atrophy. METHODS: Clinical manifestations,
      small-bowel mucosal morphology, intraepithelial inflammation and TG2-specific
      extracellular immunoglobulin A (IgA) deposits were investigated in both serum EmA
      negative and EmA-positive patients. RESULTS: 22 patients with IgA-competent
      coeliac disease were negative for serum EmA. Three of these had small-bowel
      lymphoma. Patients with EmA-negative coeliac disease were older, had abdominal
      symptoms more often, and the density of gammadelta+ intraepithelial lymphocytes
      in their intestinal mucosa was lower than in EmA-positive patients; otherwise the
      histology was similar. All serum EmA-negative patients with coeliac disease, but
      none of the disease controls, had gluten-dependent mucosal IgA deposits alongside
      TG2 in the small-bowel mucosal specimens. In vivo deposited IgA was shown to be
      TG2-specific by its ability to bind recombinant TG2. CONCLUSIONS: Negative serum
      EmA might be associated with advanced coeliac disease. TG2-targeted
      autoantibodies were deposited in the small-bowel mucosa even when absent in
      serum. This finding can be used in the diagnosis of seronegative coeliac disease
      when the histology is equivocal. It may also be helpful in the differential
      diagnosis between autoimmune enteropathy and coeliac disease.

PMID- 16571638
TI  - Occupational exposure to inhalable wood dust in the member states of the European
      Union.
AB  - The aim of this study was to estimate occupational exposure to inhalable wood
      dust by country, industry, the level of exposure and type of wood dust in 25
      member states of the European Union (EU-25) for the purposes of hazard control,
      exposure surveillance and assessment of health risks. National labour force
      statistics, a country questionnaire (in 15 member states, EU-15), a company
      survey (in Finland, France, Germany and Spain), exposure measurements (from
      Denmark, Finland, France, Germany, The Netherlands and the United Kingdom) and
      expert judgements were used to generate preliminary estimates of exposure to
      different types of wood dust. The estimates were generated according to
      industrial class (six wood industries, four other sectors) and level of exposure
      (five classes). These estimates were reviewed and finalized by national experts
      from 15 member states. Crude estimates were generated also for 10 new member
      states (EU-10). The basic data and final estimates were included in the WOODEX
      database. In 2000-2003, about 3.6 million workers (2.0% of the employed EU-25
      population) were occupationally exposed to inhalable wood dust. Of those,
      construction employed 1.2 million exposed workers (33%), mostly construction
      carpenters. The numbers of exposed workers were 700,000 (20%) in the furniture
      industry, 300,000 (9%) in the manufacture of builders' carpentry, 200,000 (5%) in
      sawmilling, 150,000 (4%) in forestry and <100,000 in other wood industries. In
      addition, there were 700,000 exposed workers (20%) in miscellaneous industries
      employing carpenters, joiners and other woodworkers. The numbers of exposed
      workers varied by country ranging from <3,000 in Luxembourg and Malta to 700,000
      in Germany. The highest exposure levels were estimated to occur in the
      construction sector and furniture industry. Due to limited exposure data there
      was considerable uncertainty in the estimates concerning construction
      woodworkers. About 560,000 workers (16% of the exposed) may be exposed to a level
      exceeding 5 mg m(-3). Mixed exposure to more than one species of wood and dust
      from wooden boards was very common, but reliable data on exposure to different
      species of wood could not be retrieved. This kind of assessment procedure
      integrating measurement data, company data, country-specific data and expert
      judgement could also serve as one model for the assessment of other occupational
      exposures.

PMID- 16571640
TI  - Role of sonic hedgehog in maintaining a pool of proliferating stem cells in the
      human fetal epidermis.
AB  - BACKGROUND: The mammalian epidermis is maintained by the ongoing proliferation of
      a subpopulation of keratinocytes known as epidermal stem cells. Sonic hedgehog
      (Shh) can regulate morphogenesis of hair follicles and several types of skin
      cancer, but the effect of Shh on proliferation of human putative epidermal stem
      cells (HPESCs) is poorly understood. METHODS AND RESULTS: We first found that
      Shh, its receptors Patched1 (Ptc1) as well as Smoothened (Smo) and its downstream
      transcription factor Gli-1 were expressed in the basal layer of human fetal
      epidermis and freshly sorted HPESCs. Next, treatment of HPESCs with media
      conditioned by Shh-N-expressing cells promoted cell proliferation, whereas
      inhibition of Shh by cyclopamine, a specific inhibitor of Shh signalling, had an
      opposite effect. Interestingly, the mitogenic effect of epidermal growth factor
      (EGF) on HPESCs was efficiently abolished by cyclopamine. Finally, bone
      morphogenetic protein 4 (BMP-4), a potential downstream effector of Shh
      signalling, increased HPESC proliferation in a concentration-dependent manner.
      CONCLUSIONS: Shh is an important regulator of HPESC proliferation in the basal
      layer of human fetal epidermis and modulates the cell responsiveness to EGF,
      which will assist to unravel the mechanisms that regulate stem cell proliferation
      and neoplasia in the human epidermis.

PMID- 16571641
TI  - Similar ovulation rates, but different follicular development with highly
      purified menotrophin compared with recombinant FSH in WHO Group II anovulatory
      infertility: a randomized controlled study.
AB  - BACKGROUND: The contribution of the LH activity in menotrophin preparations for
      ovulation induction has been investigated in small trials conducted versus FSH
      preparations. The objective of this study was to demonstrate non-inferiority of
      highly purified urinary menotrophin (HP-HMG) versus recombinant FSH (rFSH) with
      respect to the primary outcome measure, ovulation rate. METHODS: This was a
      randomized, open-label, assessor-blind, multinational study. Women with
      anovulatory infertility WHO Group II and resistant to clomiphene citrate were
      randomized (computer-generated list) to stimulation with HP-HMG (n=91) or rFSH
      (n=93) using a low-dose step-up protocol. RESULTS: The ovulation rate was 85.7%
      with HP-HMG and 85.5% with rFSH (per-protocol population), and non-inferiority
      was demonstrated. Significantly fewer intermediate-sized follicles were observed
      in the HP-HMG group (P<0.05). The singleton live birth rate was comparable
      between the two groups. The frequency of ovarian hyperstimulation syndrome and/or
      cancellation due to excessive response was 2.2% with HP-HMG and 9.8% with rFSH
      (P=0.058). CONCLUSIONS: Stimulation with HP-HMG is associated with ovulation
      rates at least as good as a rFSH in anovulatory WHO Group II women. LH activity
      modifies follicular development so that fewer intermediate-sized follicles
      develop. This could have a positive impact on the safety of ovulation induction
      protocols.

PMID- 16571643
TI  - Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis
      1.
AB  - Neurofibromatosis 1 (NF1) is a tumour suppressor gene syndrome characterized by
      multiple cutaneous and plexiform neurofibromas. Focal osseous abnormalities,
      short stature, and decreased bone mineral density are also frequent in people
      with NF1. We measured serum 25-hydroxyvitamin D concentrations in 55 patients
      with NF1 and 58 healthy controls, and correlated the findings in the patients
      with NF1 with their estimated number of dermal neurofibromas. Geometric mean (SD)
      serum 25-hydroxyvitamin D concentration was 14.0 (1.6) ng/mL among the patients
      with NF1 compared with 31.4 (1.7) ng/mL among healthy controls (p<<0.0001). The
      serum vitamin D concentration and number of dermal neurofibromas reported by
      patients with NF1 were inversely correlated (Spearman's rho = -0.572, p<0.00001).
      The occurrence of low serum vitamin D concentrations in people with NF1,
      especially those with many dermal neurofibromas, may provide new pathogenic
      insights and have important therapeutic implications.

PMID- 16571642
TI  - The human cumulus--oocyte complex gene-expression profile.
AB  - BACKGROUND: The understanding of the mechanisms regulating human oocyte
      maturation is still rudimentary. We have identified transcripts differentially
      expressed between immature and mature oocytes and cumulus cells. METHODS: Using
      oligonucleotide microarrays, genome-wide gene expression was studied in pooled
      immature and mature oocytes or cumulus cells from patients who underwent IVF.
      RESULTS: In addition to known genes, such as DAZL, BMP15 or GDF9, oocytes up
      regulated 1514 genes. We show that PTTG3 and AURKC are respectively the securin
      and the Aurora kinase preferentially expressed during oocyte meiosis. Strikingly,
      oocytes overexpressed previously unreported growth factors such as TNFSF13/APRIL,
      FGF9, FGF14 and IL4 and transcription factors including OTX2, SOX15 and SOX30.
      Conversely, cumulus cells, in addition to known genes such as LHCGR or BMPR2,
      overexpressed cell-to-cell signalling genes including TNFSF11/RANKL, numerous
      complement components, semaphorins (SEMA3A, SEMA6A and SEMA6D) and CD genes such
      as CD200. We also identified 52 genes progressively increasing during oocyte
      maturation, including CDC25A and SOCS7. CONCLUSION: The identification of genes
      that were up- and down-regulated during oocyte maturation greatly improves our
      understanding of oocyte biology and will provide new markers that signal viable
      and competent oocytes. Furthermore, genes found expressed in cumulus cells are
      potential markers of granulosa cell tumours.

PMID- 16571644
TI  - Cerebral cavernous malformation: new molecular and clinical insights.
AB  - Cerebral cavernous malformation (CCM) is a vascular malformation causing
      neurological problems, such as headaches, seizures, focal neurological deficits,
      and cerebral haemorrhages. CCMs can occur sporadically or as an autosomal
      dominant condition with variable expression and incomplete penetrance. Familial
      forms have been linked to three chromosomal loci, and loss of function mutations
      have been identified in the KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3 genes.
      Recently, many new pieces of data have been added to the CCM puzzle. It has been
      shown that the three CCM genes are expressed in neurones rather than in blood
      vessels. The interaction between CCM1 and CCM2, which was expected on the basis
      of their structure, has also been proven, suggesting a common functional pathway.
      Finally, in a large series of KRIT1 mutation carriers, clinical and
      neuroradiological features have been characterised. These data should lead to
      more appropriate follow up, treatment, and genetic counselling. The recent
      developments will also help to elucidate the precise pathogenic mechanisms
      leading to CCM, contributing to a better understanding of normal and pathological
      angiogenesis and to the development of targeted treatment.

PMID- 16571645
TI  - Polymorphisms in the xylosyltransferase genes cause higher serum XT-I activity in
      patients with pseudoxanthoma elasticum (PXE) and are involved in a severe disease
      course.
AB  - BACKGROUND: Pseudoxanthoma elasticum (PXE) is a heritable connective tissue
      disorder caused by mutations in the ABCC6 gene. Fragmentation of elastic fibres
      and deposition of proteoglycans result in a highly variable clinical picture. The
      altered proteoglycan metabolism suggests that enzymes from this pathway function
      as genetic co-factors in the severity of PXE. Therefore, we propose the XYLT
      genes encoding xylosyltransferase I (XT-I) as the chain-initiating enzyme in the
      biosynthesis of proteoglycans and the highly homologous XT-II as potential
      candidate genes. METHODS: We screened all XYLT exons in 65 German PXE patients
      using denaturing high performance liquid chromatography and analysed the
      influence of the variations on clinical characteristics. RESULTS: We identified
      22 variations in the XYLT genes. The missense variation p.A115S (XT-I) is
      associated with higher serum XT activity (p = 0.005). The amino acid substitution
      p.T801R (XT-II; c.2402C>G) occurs with significantly higher frequency in patients
      under 30 years of age at diagnosis (43% v 26%; p = 0.04); all PXE patients with
      this variation suffer from skin lesions compared to only 75% of the wild type
      patients (p = 0.002). c.166G>A, c.1569C>T, and c.2402C>G in the XYLT-II gene were
      found to be more frequent in patients with higher organ involvement (p = 0.04, p
      = 0.01, and p = 0.02, respectively). CONCLUSIONS: Here we show for the first time
      that variations in the XYLT-II gene are genetic co-factors in the severity of
      PXE. Furthermore, the higher XT activity in patients with the exchange p.A115S
      (XT-I) indicates that this polymorphism is a potential marker for increased
      remodelling of the extracellular matrix.

PMID- 16571646
TI  - Functional and clinical characterization of a mutation in KCNJ2 associated with
      Andersen-Tawil syndrome.
AB  - BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare inherited disorder,
      characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic
      features, and is caused by mutations in the gene KCNJ2, which encodes the inward
      rectifier potassium channel, Kir2.1. This study sought to analyse KCNJ2 in
      patients with familial ATS and to determine the functional characteristics of the
      mutated gene. METHODS AND RESULTS: We screened a family with inherited ATS for
      the mutation in KCNJ2, using direct DNA sequencing. A missense mutation (T75R) of
      Kir2.1, located in the highly conserved cytoplasmic N-terminal domain, was
      identified in three affected members of this family. Using the Xenopus oocyte
      expression system and whole cell voltage clamp analyses, we found that the T75R
      mutant was non-functional and possessed a strong dominant negative effect when co
      expressed with the same amount of wild type Kir2.1. Transgenic (Tg) mice
      expressing the mutated form of Kir2.1 in the heart had prolonged QTc intervals
      compared with mice expressing the wild type protein. Ventricular tachyarrhythmias
      were observed in 5 of 14 T75R-Tg mice compared with 1 of 7 Wt-Tg and none of 6
      non-transgenic littermates. In three of five T75R-Tg mice with ventricular
      tachycardia, their ECG disclosed bidirectional tachycardia as in our proband.
      CONCLUSIONS: The in vitro studies revealed that the T75R mutant of Kir2.1 had a
      strong dominant negative effect in the Xenopus oocyte expression system. It still
      preserved the ability to co-assemble and traffic to the cell membrane in
      mammalian cells. For in vivo studies, the T75R-Tg mice had bidirectional
      ventricular tachycardia after induction and longer QT intervals.

PMID- 16571648
TI  - Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer
      risk in the European Prospective Investigation into Cancer and Nutrition (EPIC
      EURGAST) study.
AB  - The risk of gastric cancer (GC) associated with dietary intake of
      nitrosodimethylamine (NDMA) and endogenous formation of nitroso compounds (NOCs)
      was investigated in the European Prospective Investigation into Cancer and
      Nutrition (EPIC). The study included 521,457 individuals and 314 incident cases
      of GC that had occurred after 6.6 average years of follow-up. An index of
      endogenous NOC (ENOC) formation was estimated using data of the iron content from
      meat intake and faecal apparent total NOC formation according to previous
      published studies. Antibodies to Helicobacter pylori and vitamin C levels were
      measured in a sub-sample of cases and matched controls included in a nested case
      control within the cohort. Exposure to NDMA was < 1 microg on average compared
      with 93 mug on average from ENOC. There was no association between NDMA intake
      and GC risk (HR, 1.00; 95% CI, 0.7-1.43). ENOC was significantly associated with
      non-cardia cancer risk (HR, 1.42; 95% CI, 1.14-1.78 for an increase of 40
      microg/day) but not with cardia cancer (HR, 0.96; 95% CI, 0.69-1.33). Although
      the number of not infected cases is low, our data suggest a possible interaction
      between ENOC and H.pylori infection (P for interaction = 0.09). Moreover, we
      observed an interaction between plasma vitamin C and ENOC (P < 0.02). ENOC
      formation may account for our previously reported association between red and
      processed meat consumption and gastric cancer risk.

PMID- 16571649
TI  - The XPD 751Gln allele is associated with an increased risk for esophageal
      adenocarcinoma: a population-based case-control study in Sweden.
AB  - Mechanisms behind the strong associations of esophageal adenocarcinoma risk with
      gastroesophageal reflux (GOR) and body mass remain to be defined. In a nationwide
      population-based case-control study, we examined associations of polymorphisms in
      the DNA repair genes XPD, XPC, XRCC1 and XRCC3 with risk of esophageal
      adenocarcinoma, squamous-cell carcinoma (SCC) and gastric cardia adenocarcinoma,
      and paid special attention to possible interactions with symptomatic reflux or
      body mass. We collected blood samples from 96, 81 and 126 interviewed incident
      cases of esophageal adenocarcinoma, esophageal SCC and gastric cardia
      adenocarcinoma, respectively, and 472 randomly selected controls, frequency
      matched with regard to age and sex. DNA was extracted and polymorphisms in XPD
      codon 751 (Lys-->Gln), codon 312 (Asp-->Asn), C insertion in intron 10 of XPD,
      XPC codon 939 (Lys-->Gln), XRCC1 codon 399 (Arg-->Gln) and XRCC3 codon 241 (Thr-
      >Met) were examined using PCR-RFLP. Odds ratios (ORs) derived from multivariate
      logistic regression with adjustments for potential confounding factors estimated
      relative risks. XPD codon 751 Lys/Gln and Gln/Gln genotypes, compared with
      Lys/Lys genotype, were both associated with a more than doubled risk for
      esophageal adenocarcinoma (OR=2.4; 95% CI=1.4-4.4; OR=2.7, 95% CI=1.3-5.9). The
      combined effects of these genotypes and symptomatic GOR or body mass showed
      borderline significant deviation from additivity. Excess risks for esophageal SCC
      were also noted for XPD 751Gln variant genotypes. Other studied variants were not
      found to be related to the three tumors. Our study suggests that XPD 751Gln
      allele is a potential genetic marker for susceptibility to esophageal
      adenocarcinoma.

PMID- 16571650
TI  - Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that
      is inversely correlated with functional PTEN.
AB  - The tumor suppressor PTEN antagonizes phosphatidylinositol 3-kinase (PI3K), which
      contributes to tumorigenesis in many cancer types. While PTEN mutations occur in
      some melanomas, their precise mechanistic consequences have yet to be elucidated.
      We sought to identify novel downstream effectors of PI3K using a combination of
      genomic and functional tests. Microarray analysis of 53 melanoma cell lines
      identified 610 genes differentially expressed (P<0.05) between wild-type lines
      and those with PTEN aberrations. Many of these genes are known to be involved in
      the PI3K pathway and other signaling pathways influenced by PTEN. Validation of
      differential gene expression by qRT-PCR was performed in the original 53 cell
      lines and an independent set of 18 melanoma lines with known PTEN status.
      Osteopontin (OPN), a secreted glycophosphoprotein that contributes to tumor
      progression, was more abundant at both the mRNA and protein level in PTEN
      mutants. The inverse correlation between OPN and PTEN expression was validated
      (P<0.02) by immunohistochemistry using melanoma tissue microarrays. Finally,
      treatment of cell lines with the PI3K inhibitor LY294002 caused a reduction in
      expression of OPN. These data indicate that OPN acts downstream of PI3K in
      melanoma and provides insight into how PTEN loss contributes to melanoma
      development.

PMID- 16571651
TI  - Sulforaphane enhances TRAIL-induced apoptosis through the induction of DR5
      expression in human osteosarcoma cells.
AB  - Sulforaphane (SFN), a naturally occurring isothiocyanate, is an attractive agent
      because of its potent anticancer effects. SFN suppresses the proliferation of
      various cancer cells in vitro and in vivo. Tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) is also one of the most promising candidates
      for cancer therapeutics owing to its ability to selectively induce apoptosis in
      tumor cells. In this study, we report that SFN enhances TRAIL-induced apoptosis
      in human osteosarcoma cells, Saos2 and MG63. The apoptosis induced by co
      treatment with SFN and TRAIL was markedly blocked by a dominant negative form of
      the TRAIL receptor or caspase inhibitors. The combined use of SFN and TRAIL
      effectively induced Bid cleavage and the activation of caspases 8, 10, 9 and 3 at
      ineffective concentrations for each agent. SFN upregulated the expression of
      death receptor 5 (DR5), a receptor for TRAIL, at mRNA and protein levels in a
      dose-dependent manner. In addition, the SFN-mediated sensitization to TRAIL was
      reduced by DR5 siRNA, suggesting that the sensitization was at least partially
      mediated through the induction of DR5 expression. Furthermore, SFN sensitized
      TRAIL-induced apoptosis in a p53-independent manner. On the other hand, SFN
      neither induced DR5 protein expression or enhanced TRAIL-induced apoptosis in
      normal human peripheral blood mononuclear cells. Thus, combined treatment with
      SFN and TRAIL might be a promising therapy for osteosarcoma.

PMID- 16571652
TI  - Identification of tubulin as the molecular target of proapoptotic pyrrolo-1,5
      benzoxazepines.
AB  - We have demonstrated previously that certain members of a series of novel pyrrolo
      1,5-benzoxazepine (PBOX) compounds potently induce apoptosis in a variety of
      human chemotherapy-resistant cancer cell lines and in primary ex vivo material
      derived from cancer patients. A better understanding of the molecular mechanisms
      underlying the apoptotic effects of these PBOX compounds is essential to their
      development as antineoplastic therapeutic agents. This study sought to test the
      hypothesis that proapoptotic PBOX compounds target the microtubules. We show that
      a representative proapoptotic PBOX compound, PBOX-6, induces apoptosis in both
      the MCF-7 and K562 cell lines. An accumulation of cells in G2/M precedes
      apoptosis in response to PBOX-6. PBOX-6 induces prometaphase arrest and causes an
      accumulation of cyclin B1 levels and activation of cyclin B1/CDK1 kinase in a
      manner similar to that of two representative antimicrotubule agents, nocodazole
      and paclitaxel. Indirect immunofluorescence demonstrates that both PBOX-6 and
      another pro-apoptotic PBOX compound, PBOX-15, cause microtubule depolymerization
      in MCF-7 cells. They also inhibit the assembly of purified tubulin in vitro,
      whereas a nonapoptotic PBOX compound (PBOX-21) has no effect on either the
      cellular microtubule network or on the assembly of purified tubulin. This
      suggests that the molecular target of the pro-apoptotic PBOX compounds is
      tubulin. PBOX-6 does not bind to either the vinblastine or the colchicine binding
      site on tubulin, suggesting that it binds to an as-yet-uncharacterised novel site
      on tubulin. The ability of PBOX-6 to bind tubulin and cause microtubule
      depolymerization confirms it as a novel candidate for antineoplastic therapy.

PMID- 16571653
TI  - A cannabinoid quinone inhibits angiogenesis by targeting vascular endothelial
      cells.
AB  - Recent findings on the inhibition of angiogenesis and vascular endothelial cell
      proliferation by anthracycline antibiotics, which contain a quinone moiety, make
      this type of compound a very promising lead in cancer research/therapy. We have
      reported that a new cannabinoid anticancer quinone, cannabidiol hydroxyquinone
      (HU-331), is highly effective against tumor xenografts in nude mice. For
      evaluation of the antiangiogenic action of cannabinoid quinones, collagen
      embedded rat aortic ring assay was used. The ability of cannabinoids to cause
      endothelial cell apoptosis was assayed by TUNEL staining and flow cytometry
      analysis. To examine the genes and pathways targeted by HU-331 in vascular
      endothelial cells, human cDNA microarrays and polymerase chain reaction were
      used. Immunostaining with anti-CD31 of tumors grown in nude mice served to
      indicate inhibition of tumor angiogenesis. HU-331 was found to be strongly
      antiangiogenic, significantly inhibiting angiogenesis at concentrations as low as
      300 nM. HU-331 inhibited angiogenesis by directly inducing apoptosis of vascular
      endothelial cells without changing the expression of pro- and antiangiogenic
      cytokines and their receptors. A significant decrease in the total area occupied
      by vessels in HU-331-treated tumors was also observed. These data lead us to
      consider HU-331 to have high potential as a new antiangiogenic and anticancer
      drug.

PMID- 16571647
TI  - The molecular genetics of Marfan syndrome and related disorders.
AB  - Marfan syndrome (MFS), a relatively common autosomal dominant hereditary disorder
      of connective tissue with prominent manifestations in the skeletal, ocular, and
      cardiovascular systems, is caused by mutations in the gene for fibrillin-1
      (FBN1). The leading cause of premature death in untreated individuals with MFS is
      acute aortic dissection, which often follows a period of progressive dilatation
      of the ascending aorta. Recent research on the molecular physiology of fibrillin
      and the pathophysiology of MFS and related disorders has changed our
      understanding of this disorder by demonstrating changes in growth factor
      signalling and in matrix-cell interactions. The purpose of this review is to
      provide a comprehensive overview of recent advances in the molecular biology of
      fibrillin and fibrillin-rich microfibrils. Mutations in FBN1 and other genes
      found in MFS and related disorders will be discussed, and novel concepts
      concerning the complex and multiple mechanisms of the pathogenesis of MFS will be
      explained.

PMID- 16571655
TI  - Experimental taphonomy shows the feasibility of fossil embryos.
AB  - The recent discovery of apparent fossils of embryos contemporaneous with the
      earliest animal remains may provide vital insights into the metazoan radiation.
      However, although the putative fossil remains are similar to modern marine animal
      embryos or larvae, their simple geometric forms also resemble other organic and
      inorganic structures. The potential for fossilization of animals at such
      developmental stages and the taphonomic processes that might affect preservation
      before mineralization have not been examined. Here, we report experimental
      taphonomy of marine embryos and larvae similar in size and inferred cleavage mode
      to presumptive fossil embryos. Under conditions that prevent autolysis, embryos
      within the fertilization envelope can be preserved with good morphology for
      sufficiently long periods for mineralization to occur. The reported fossil record
      exhibits size bias, but we show that embryo size is unlikely to be a major factor
      in preservation. Under some conditions of death, fossilized remains will not
      accurately reflect the cell structure of the living organism. Although embryos
      within the fertilization envelope have high preservation potential, primary
      larvae have negligible preservation potential. Thus the paleo-embryological
      record may have strong biases on developmental stages preserved. Our data provide
      a predictive basis for interpreting the fossil record to unravel the evolution of
      ontogeny in the origin of metazoans.

PMID- 16571654
TI  - Sphingosine and its analog, the immunosuppressant 2-amino-2-(2-[4
      octylphenyl]ethyl)-1,3-propanediol, interact with the CB1 cannabinoid receptor.
AB  - Sphingosine-1-phosphate (S1P) and cannabinoid receptors are G-protein-coupled
      receptors that mediate the effects of S1P and endocannabinoids, respectively.
      Cannabinoid receptors also mediate the effects of Delta9-tetrahydrocannabinol,
      the primary psychoactive ingredient in marijuana, whereas S1P receptors
      contribute to the immunosuppressant effects of 2-amino-2-(2-[4-octylphenyl]ethyl)
      1,3-propanediol (FTY720). FTY720 is a sphingosine analog that can prevent renal
      graft rejections and suppress a variety of autoimmune disorders in animal models
      and clinical trials. We now report that both FTY720 and sphingosine interact with
      CB1 but not CB2 cannabinoid receptors. FTY720 and sphingosine inhibited the
      binding of the CB1-selective antagonist [3H]N-(piperidinyl)-5-(4-chlorophenyl)-1
      (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide ([3H]SR141716A) and the
      cannabinoid agonist [3H](-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans
      4-(3-hydroxypropyl)cyclohexanol ([3H]CP55,940) in a concentration-dependent
      manner in both CB1-expressing cell lines and mouse cerebellum. However, these
      compounds did not significantly alter [3H]CP55,940 binding to CB2 receptors. In G
      protein activation assays, FTY720 and sphingosine inhibited the maximal
      stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding by the
      cannabinoid agonist R-(+)-[2,3-dihydro-5-methyl-3
      [(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1
      naphthalenyl)methanone mesylate (WIN55,212-2) in a concentration-dependent
      manner, and this antagonist effect was not mimicked by S1P. FTY720 and
      sphingosine also inhibited activation of extracellular signal-regulated kinases 1
      and 2 and Akt by WIN55,212-2 in intact Chinese hamster ovary (CHO) cells
      expressing CB1 receptors and attenuated WIN55,212-2-stimulated internalization of
      a fluorescence-tagged CB1 receptor in CHO cells. Moreover, both FTY720 and
      sphingosine produced rightward shifts in the concentration-effect curves of
      cannabinoid agonists for G-protein activation, indicating that they act as
      competitive CB1 antagonists. These results suggest that the CB1 receptor could be
      a novel target of FTY720 and that sphingosine could be an endogenous CB11
      antagonist.

PMID- 16571656
TI  - Characterization of mitochondrial ferritin in Drosophila.
AB  - Mitochondrial function depends on iron-containing enzymes and proteins, whose
      maturation requires available iron for biosynthesis of iron-sulfur clusters and
      heme. Little is known about how mitochondrial iron homeostasis is maintained,
      although the recent discovery of a mitochondrial ferritin in mammals and plants
      has uncovered a potential key player in the process. Here, we show that
      Drosophila melanogaster expresses mitochondrial ferritin from an intron
      containing gene. It has high similarity to the mouse and human mitochondrial
      ferritin sequences and, as in mammals, is expressed mainly in testis. This
      ferritin contains a putative mitochondrial targeting sequence and an epitope
      tagged version localizes to mitochondria in transfected cells. Overexpression of
      mitochondrial ferritin fails to alter both total-body iron levels and iron that
      is bound to secretory ferritins. However, the viability of iron-deficient flies
      is compromised by overexpression of mitochondrial ferritin, suggesting that it
      may sequester iron at the expense of other important cellular functions. The
      conservation of mitochondrial ferritin in an insect species underscores the
      importance of this iron-storage molecule.

PMID- 16571657
TI  - On the nature of low- and high-affinity EGF receptors on living cells.
AB  - The small subpopulation of high-affinity EGF receptors (EGFRs) on living cells
      revealed by Scatchard analysis of (125)I-EGF binding results was discovered
      nearly three decades ago, yet not much is known about the underlying mechanism.
      After the determination of the structure of different forms of EGFR extracellular
      domain it was proposed that the monomeric tethered configuration corresponds to
      the majority of low-affinity receptors, whereas the extended dimeric
      configuration corresponds to the minority of the high-affinity class of EGFRs.
      Mathematical modeling of EGF-binding experiments to different conformational
      mutants of EGFR has shown that the high-affinity class of EGFR on living cells
      does not correspond to the extended configuration of EGFR and can only be
      accounted for by including in the mathematical model an additional binding event
      that is attributed to the dynamic nature of EGFR on living cells. To circumvent
      this problem we have performed similar experiments in the background of an EGFR
      mutant that does not form high-affinity sites. Quantitative analysis and
      mathematical modeling of these data show that release of the intramolecular
      tether causes a 2-fold increase in EGF-binding affinity, whereas elimination of
      the dimerization arm reduces EGF-binding affinity by approximately 6-fold. These
      experiments confirm the salient features of the structural model for EGFR
      regulation and argue further that the intramolecular tether provides only limited
      autoinhibitory control of EGFR activity and that the low-affinity class of EGF
      binding sites on living cells reflects interconverting, tethered, and extended
      receptor configurations.

PMID- 16571658
TI  - A role of the double-stranded RNA-binding protein PACT in mouse ear development
      and hearing.
AB  - To determine the physiological functions of the mammalian double-stranded RNA
      binding protein PACT, the single-copy mouse Pact gene was disrupted and
      expression of the protein was completely ablated. The most notable phenotypes of
      the Pact(-/-) mouse were reduced size and severe microtia. As a result of the
      congenital abnormality of both outer and middle ears, these mice were hearing
      impaired. In situ hybridization revealed that PACT mRNA was expressed in specific
      regions of all three parts of the ear in adult and embryonic wild-type mice. Our
      study demonstrated an essential role of PACT in mammalian ear development and
      produced the first animal model for studying human microtia.

PMID- 16571659
TI  - Histone H3 variants and their potential role in indexing mammalian genomes: the
      "H3 barcode hypothesis".
AB  - In the history of science, provocative but, at times, controversial ideas have
      been put forward to explain basic problems that confront and intrigue the
      scientific community. These hypotheses, although often not correct in every
      detail, lead to increased discussion that ultimately guides experimental tests of
      the principal concepts and produce valuable insights into long-standing
      questions. Here, we present a hypothesis, the "H3 barcode hypothesis." Hopefully,
      our ideas will evoke critical discussion and new experimental approaches that
      bear on general topics, such as nuclear architecture, epigenetic memory, and cell
      fate choice. Our hypothesis rests on the central concept that mammalian histone
      H3 variants (H3.1, H3.2, and H3.3), although remarkably similar in amino acid
      sequence, exhibit distinct posttranslational "signatures" that create different
      chromosomal domains or territories, which, in turn, influence epigenetic states
      during cellular differentiation and development. Although we restrict our
      comments to H3 variants in mammals, we expect that the more general concepts
      presented here will apply to other histone variant families in organisms that
      employ them.

PMID- 16571660
TI  - Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated
      neuroprotection.
AB  - Focal cerebral ischemia and traumatic brain injury induce an escalating amount of
      cell death because of harmful mediators diffusing from the original lesion site.
      Evidence suggests that healthy cells surrounding these lesions attempt to protect
      themselves by producing endocannabinoids (eCBs) and activating cannabinoid
      receptors, the molecular target for marijuana-derived compounds. Indeed,
      activation of cannabinoid receptors reduces the production and diffusion of
      harmful mediators. Here, we provide evidence that an exception to this pattern is
      found in experimental autoimmune encephalomyelitis (EAE), a mouse model of
      multiple sclerosis. We show that cell damage induced by EAE does not lead to
      increase in eCBs, even though cannabinoid receptors are functional because
      synthetic cannabinoid agonists are known to confine EAE-induced lesions. This
      lack of eCB increase is likely due to IFN-gamma, which is released by primed T
      cells invading the CNS. We show that IFN-gamma disrupts the functionality of
      purinergic P2X7 receptors, a key step controlling eCB production by microglia,
      the main source of eCBs in brain. Accordingly, induction of EAE in P2X7-/- mice
      results in even lower eCB levels and more pronounced cell damage than in wild
      type mice. Our data suggest that the high level of CNS IFN-gamma associated with
      EAE disrupts eCB-mediated neuroprotection while maintaining functional
      cannabinoid receptors, thus providing additional support for the use of
      cannabinoid-based medicine to treat multiple sclerosis.

PMID- 16571661
TI  - Controlled release of proteins from polymer-modified surfaces.
AB  - The ability to control the rate of adsorption and desorption of proteins from
      surfaces is studied by using a molecular theory. We show how changing the
      chemical structure and charge of short linear and branched grafted polymers to an
      electrode surface can be used to promote fast adsorption of charged proteins on a
      time scale of seconds and control the desorption in a time scale ranging from
      milliseconds to hours. The optimal controlled release is found from the interplay
      of electrostatic attractions at short distances from the surface and the proper
      electrostatic and steric repulsive barrier at distances from the surfaces larger
      than the proteins' size. The implications of our results to the design of
      controlled-release devices is discussed.

PMID- 16571662
TI  - Malaria resurgence in the East African highlands: temperature trends revisited.
AB  - The incidence of malaria in the East African highlands has increased since the
      end of the 1970s. The role of climate change in the exacerbation of the disease
      has been controversial, and the specific influence of rising temperature
      (warming) has been highly debated following a previous study reporting no
      evidence to support a trend in temperature. We revisit this result using the same
      temperature data, now updated to the present from 1950 to 2002 for four high
      altitude sites in East Africa where malaria has become a serious public health
      problem. With both nonparametric and parametric statistical analyses, we find
      evidence for a significant warming trend at all sites. To assess the biological
      significance of this trend, we drive a dynamical model for the population
      dynamics of the mosquito vector with the temperature time series and the
      corresponding detrended versions. This approach suggests that the observed
      temperature changes would be significantly amplified by the mosquito population
      dynamics with a difference in the biological response at least 1 order of
      magnitude larger than that in the environmental variable. Our results emphasize
      the importance of considering not just the statistical significance of climate
      trends but also their biological implications with dynamical models.

PMID- 16571663
TI  - Connexin30.2 containing gap junction channels decelerate impulse propagation
      through the atrioventricular node.
AB  - In the mammalian heart, gap junction channels between electrically coupled
      cardiomyocytes are necessary for impulse propagation and coordinated contraction
      of atria and ventricles. Recently, mouse connexin30.2 (Cx30.2) was shown to be
      expressed in the cardiac conduction system, predominantly in sinoatrial and
      atrioventricular (AV) nodes. The corresponding gap junctional channels expressed
      in HeLa cells exhibit the lowest unitary conductance (9 pS) of all connexin
      channels. Here we report that Cx30.2 slows down the propagation of excitation
      through the AV node. Mice expressing a LacZ reporter gene instead of the Cx30.2
      coding region (Cx30.2(LacZ/LacZ)) exhibit a PQ interval that is approximately 25%
      shorter than in WT littermates. By recording atrial, His, and ventricular signals
      with intracardiac electrodes, we show that this decrease is attributed to
      significantly accelerated conduction above the His bundle (atrial-His interval:
      27.9 +/- 5.1 ms in Cx30.2(LacZ/LacZ) versus 37.1 +/- 4.1 ms in Cx30.2(+/+) mice),
      whereas HV conduction is unaltered. Atrial stimulation revealed an elevated AV
      nodal conduction capacity and faster ventricular response rates during induced
      episodes of atrial fibrillation in Cx30.2(LacZ/LacZ) mice. Our results show that
      Cx30.2 contributes to the slowdown of impulse propagation in the AV node and
      additionally limits the maximum number of beats conducted from atria to
      ventricles. Thus, it is likely to be involved in coordination of atrial and
      ventricular contraction and to fulfill a protective role toward
      pathophysiological states such as atrial tachyarrhythmias (e.g., atrial
      fibrillation) by preventing rapid conduction to the ventricles potentially
      associated with hemodynamic deterioration.

PMID- 16571666
TI  - Peanut lectin stimulates proliferation of colon cancer cells by interaction with
      glycosylated CD44v6 isoforms and consequential activation of c-Met and MAPK:
      functional implications for disease-associated glycosylation changes.
AB  - Peanut agglutinin lectin (PNA) binds the Thomsen-Friedenreich (TF) oncofetal
      carbohydrate antigen (galactose beta1-3N-acetylgalactosamine alpha) that shows
      increased expression in colon cancer, adenomas, and inflammatory bowel disease.
      PNA is mitogenic, both in vitro and in vivo, for colon epithelial cells. In these
      cells, PNA binds predominantly to cell-surface TF antigen expressed by high
      molecular weight isoforms of the transmembrane glycoprotein CD44 that are
      generated in inflamed and neoplastic colonic epithelia by altered RNA splicing.
      Our aim was to identify the signaling mechanism underlying the proliferative
      response to PNA. This was investigated in HT29, T84, and Caco2 colon cancer
      cells. Parallel lectin and immunoblotting of PNA affinity-purified HT29 cell
      membrane extracts showed PNA binding to high molecular weight CD44v6 isoforms.
      Within 5 min, PNA (25 microg/mL) caused a 6-fold increase in phosphorylation of
      hepatocyte growth factor receptor c-Met, known to co-associate with CD44v6. This
      was followed by the downstream activation of p44/p42 mitogen-activated protein
      kinase (MAPK) over 15-20 min. The presence of 100 microg/mL asialofetuin, a TF
      antigen-expressing glycoprotein, blocked both PNA-induced c-Met and MAPK
      activation. A similar PNA-induced c-Met and MAPK phosphorylation was also seen in
      T84 cells that express CD44v6 but not in Caco2 cells that lack CD44v6. PNA
      induced cell proliferation was completely blocked by 1 microM PD98059, an
      inhibitor of MAPK activation (p < 0.0001). The expression of TF antigen by CD44
      isoforms in colonic epithelial cells allows lectin-induced mitogenesis that is
      mediated by phosphorylation of c-Met and MAPK. It provides a mechanism by which
      dietary, microbial, or endogenous galactose-binding lectins could affect
      epithelial proliferation in the cancerous and precancerous colon.

PMID- 16571664
TI  - Structure of human Wilson protein domains 5 and 6 and their interplay with domain
      4 and the copper chaperone HAH1 in copper uptake.
AB  - Human Wilson protein is a copper-transporting ATPase located in the secretory
      pathway possessing six N-terminal metal-binding domains. Here we focus on the
      function of the metal-binding domains closest to the vesicular portion of the
      copper pump, i.e., domain 4 (WLN4), and a construct of domains 5 and 6 (WLN5-6).
      For comparison purposes, some experiments were also performed with domain 2
      (WLN2). The solution structure of apoWLN5-6 consists of two ferredoxin folds
      connected by a short linker, and (15)N relaxation rate measurements show that it
      behaves as a unit in solution. An NMR titration of apoWLN5-6 with the
      metallochaperone Cu(I)HAH1 reveals no complex formation and no copper exchange
      between the two proteins, whereas titration of Cu(I)HAH1 with WLN4 shows the
      formation of an adduct that is in fast exchange on the NMR time scale with the
      isolated protein species as confirmed by (15)N relaxation data. A similar
      interaction is also observed between Cu(I)HAH1 and WLN2; however, the relative
      amount of the adduct in the protein mixture is lower. An NMR titration of apoWLN5
      6 with Cu(I)WLN4 shows copper transfer, first to WLN6 then to WLN5, without the
      formation of an adduct. Therefore, we suggest that WLN4 and WLN2 are two
      acceptors of Cu(I) from HAH1, which then somehow route copper to WLN5-6, before
      the ATP-driven transport of copper across the vesicular membrane.

PMID- 16571665
TI  - Fibrillin expression is regulated by abscisic acid response regulators and is
      involved in abscisic acid-mediated photoprotection.
AB  - Fibrillins are lipid-binding proteins of plastids that are induced under abiotic
      stress conditions. In response to environmental stress, plants generate abscisic
      acid (ABA) as an endogenous signal. We show that ABA treatment and fibrillin
      accumulation enhance the tolerance of photosystem II toward light stress
      triggered photoinhibition in Arabidopsis. ABA induces fibrillin accumulation, and
      the ABA response regulators ABI1 and ABI2 regulate fibrillin expression. The
      abundance of fibrillin transcripts was specifically reduced in the ABA
      insensitive abi1 mutant but not in the abi2 mutant. However, leaves of abi2
      revealed in comparison to WT and abi1 enhanced fibrillin levels, pointing to a
      posttranscriptional control mechanism. Protein interaction analysis identified
      the protein phosphatase ABI2 to target the preprotein of fibrillin. Interaction
      was abrogated either by deleting the signal peptide of prefibrillin or by the
      single amino acid exchange present in the phosphatase-deficient abi2 protein.
      Thus, ABI1 and ABI2 seem to control fibrillin expression that is involved in
      mediating ABA-induced photoprotection.

PMID- 16571667
TI  - Endogenously produced ganglioside GM3 endows etoposide and doxorubicin resistance
      by up-regulating Bcl-2 expression in 3LL Lewis lung carcinoma cells.
AB  - The ganglioside patterns have been shown to dramatically change during cell
      proliferation and differentiation and in certain cell-cycle phases, brain
      development, and cancer malignancy. To investigate the significance of the
      ganglioside GM3 in cancer malignancy, we established GM3-reconstituted cells by
      transfecting the cDNA of GM3 synthase into a GM3-deficient subclone of the 3LL
      Lewis lung carcinoma cell line (Uemura, S. (2003) Glycobiology, 13, 207-216). The
      GM3-reconstituted cells were resistant to apoptosis induced by etoposide and
      doxorubicin. There were no changes in the expression levels of topoisomerase
      IIalpha or P-glycoprotein, or in the uptake of doxorubicin between the GM3
      reconstituted cells and the mock-transfected cells. To understand the mechanism
      of the etoposide-resistant phenotype acquired in the GM3-reconstituted cells, we
      investigated their apoptotic signaling. Although no difference was observed in
      the phosphorylation of p53 at serine-15-residue site by etoposide between the GM3
      reconstituted cells and mock-transfected cells, the activation of both caspase-3
      and caspase-9 was specifically inhibited in the former. We found that the anti
      apoptotic protein B-cell leukemia/lymphoma 2 (Bcl-2) was increased in the GM3
      reconstituted cells. Moreover, wild-type 3LL Lewis lung carcinoma cells, which
      have an abundance of GM3, exhibited no DNA fragmentation following etoposide
      treatment and expressed higher levels of the Bcl-2 protein compared with the J5
      subclone. Thus, these results support the conclusion that endogenously produced
      GM3 is involved in malignant phenotypes, including anticancer drug resistance
      through up-regulating the Bcl-2 protein in this lung cancer cell line.

PMID- 16571668
TI  - Disruption of the A-kinase anchoring domain in flagellar radial spoke protein 3
      results in unregulated axonemal cAMP-dependent protein kinase activity and
      abnormal flagellar motility.
AB  - Biochemical studies of Chlamydomonas flagellar axonemes revealed that radial
      spoke protein (RSP) 3 is an A-kinase anchoring protein (AKAP). To determine the
      physiological role of PKA anchoring in the axoneme, an RSP3 mutant, pf14, was
      transformed with an RSP3 gene containing a mutation in the PKA-binding domain.
      Analysis of several independent transformants revealed that the transformed cells
      exhibit an unusual phenotype: a fraction of the cells swim normally; the
      remainder of the cells twitch feebly or are paralyzed. The abnormal/paralyzed
      motility is not due to an obvious deficiency of radial spoke assembly, and the
      phenotype cosegregates with the mutant RSP3. We postulated that paralysis was due
      to failure in targeting and regulation of axonemal cAMP-dependent protein kinase
      (PKA). To test this, reactivation experiments of demembranated cells were
      performed in the absence or presence of PKA inhibitors. Importantly, motility in
      reactivated cell models mimicked the live cell phenotype with nearly equal
      fractions of motile and paralyzed cells. PKA inhibitors resulted in a twofold
      increase in the number of motile cells, rescuing paralysis. These results confirm
      that flagellar RSP3 is an AKAP and reveal that a mutation in the PKA binding
      domain results in unregulated axonemal PKA activity and inhibition of normal
      motility.

PMID- 16571669
TI  - Oxysterol-binding protein and vesicle-associated membrane protein-associated
      protein are required for sterol-dependent activation of the ceramide transport
      protein.
AB  - Sphingomyelin (SM) and cholesterol are coregulated metabolically and associate
      physically in membrane microdomains involved in cargo sorting and signaling. One
      mechanism for regulation of this metabolic interface involves oxysterol binding
      protein (OSBP) via high-affinity binding to oxysterol regulators of cholesterol
      homeostasis and activation of SM synthesis at the Golgi apparatus. Here, we show
      that OSBP regulation of SM synthesis involves the endoplasmic reticulum (ER)-to
      Golgi ceramide transport protein (CERT). RNA interference (RNAi) experiments in
      Chinese hamster ovary (CHO)-K1 cells revealed that OSBP and vesicle-associated
      membrane protein-associated protein (VAP) were required for stimulation of CERT
      dependent ceramide transport and SM synthesis by 25-hydroxycholesterol and
      cholesterol depletion in response to cyclodextrin. Additional RNAi experiments in
      human embryonic kidney 293 cells supported OSBP involvement in oxysterol
      activated SM synthesis and also revealed a role for OSBP in basal SM synthesis.
      Activation of ER-to-Golgi ceramide transport in CHO-K1 cells required interaction
      of OSBP with the ER and Golgi apparatus, OSBP-dependent Golgi translocation of
      CERT, and enhanced CERT-VAP interaction. Regulation of CERT by OSBP, sterols, and
      VAP reveals a novel mechanism for integrating sterol regulatory signals with
      ceramide transport and SM synthesis in the Golgi apparatus.

PMID- 16571670
TI  - Engrailed-1 negatively regulates beta-catenin transcriptional activity by
      destabilizing beta-catenin via a glycogen synthase kinase-3beta-independent
      pathway.
AB  - The Wnt signaling pathway plays a major role in development, and upon
      deregulation it is implicated in neoplasia. The hallmark of the canonical Wnt
      signal is the protection of beta-catenin from ubiquitination and proteasomal
      degradation induced by glycogen synthase kinase (GSK)-3beta inhibition. The
      stabilized beta-catenin translocates to the nucleus where it binds to T-cell
      factor/lymphoid enhancer factor (TCF/LEF) transcription factors, activating the
      expression of Wnt target genes. In the absence of Wnt signal, TCF/LEF bind to
      Groucho (Gro)/TLE corepressors and repress Wnt target genes. Gro/TLE bind also to
      Engrailed (En) transcription factors mediating En-repressive activity on En
      target genes. Here, we present data suggesting that En-1 serves also as a
      negative regulator of beta-catenin transcriptional activity; however, its
      repressive effect is independent of Gro/TLE. Our data suggest that En-1 acts by
      destabilizing beta-catenin via a proteasomal degradation pathway that is GSK
      3beta-independent. Moreover, because En-1-mediated beta-catenin degradation is
      also Siah independent, our data imply that En-1 exerts its repressive effect by a
      novel mechanism negatively controlling the level of beta-catenin.

PMID- 16571671
TI  - Myosin VI stabilizes an actin network during Drosophila spermatid
      individualization.
AB  - Here, we demonstrate a new function of myosin VI using observations of Drosophila
      spermatid individualization in vivo. We find that myosin VI stabilizes a branched
      actin network in actin structures (cones) that mediate the separation of the
      syncytial spermatids. In a myosin VI mutant, the cones do not accumulate F-actin
      during cone movement, whereas overexpression of myosin VI leads to bigger cones
      with more F-actin. Myosin subfragment 1-fragment decoration demonstrated that the
      actin cone is made up of two regions: a dense meshwork at the front and parallel
      bundles at the rear. The majority of the actin filaments were oriented with their
      pointed ends facing in the direction of cone movement. Our data also demonstrate
      that myosin VI binds to the cone front using its motor domain. Fluorescence
      recovery after photobleach experiments using green fluorescent protein-myosin VI
      revealed that myosin VI remains bound to F-actin for minutes, suggesting its role
      is tethering, rather than transporting cargo. We hypothesize that myosin VI
      protects the actin cone structure either by cross-linking actin filaments or
      anchoring regulatory molecules at the cone front. These observations uncover a
      novel mechanism mediated by myosin VI for stabilizing long-lived actin structures
      in cells.

PMID- 16571672
TI  - NuSAP, a mitotic RanGTP target that stabilizes and cross-links microtubules.
AB  - Nucleolar and spindle-associated protein (NuSAP) was recently identified as a
      microtubule- and chromatin-binding protein in vertebrates that is nuclear during
      interphase. Small interfering RNA-mediated depletion of NuSAP resulted in
      aberrant spindle formation, missegregation of chromosomes, and ultimately blocked
      cell proliferation. We show here that NuSAP is enriched on chromatin-proximal
      microtubules at meiotic spindles in Xenopus oocytes. When added at higher than
      physiological levels to Xenopus egg extract, NuSAP induces extensive bundling of
      spindle microtubules and causes bundled microtubules within spindle-like
      structures to become longer. In vitro reconstitution experiments reveal two
      direct effects of NuSAP on microtubules: first, it can efficiently stabilize
      microtubules against depolymerization, and second, it can cross-link large
      numbers of microtubules into aster-like structures, thick fibers, and networks.
      With defined components we show that the activity of NuSAP is differentially
      regulated by Importin (Imp) alpha, Impbeta, and Imp7. While Impalpha and Imp7
      appear to block the microtubule-stabilizing activity of NuSAP, Impbeta
      specifically suppresses aspects of the cross-linking activity of NuSAP. We
      propose that to achieve full NuSAP functionality at the spindle, all three
      importins must be dissociated by RanGTP. Once activated, NuSAP may aid to
      maintain spindle integrity by stabilizing and cross-linking microtubules around
      chromatin.

PMID- 16571673
TI  - Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis
      elegans.
AB  - Rab small GTPases are involved in the transport of vesicles between different
      membranous organelles. RAB-3 is an exocytic Rab that plays a modulatory role in
      synaptic transmission. Unexpectedly, mutations in the Caenorhabditis elegans RAB
      3 exchange factor homologue, aex-3, cause a more severe synaptic transmission
      defect as well as a defecation defect not seen in rab-3 mutants. We hypothesized
      that AEX-3 may regulate a second Rab that regulates these processes with RAB-3.
      We found that AEX-3 regulates another exocytic Rab, RAB-27. Here, we show that C.
      elegans RAB-27 is localized to synapse-rich regions pan-neuronally and is also
      expressed in intestinal cells. We identify aex-6 alleles as containing mutations
      in rab-27. Interestingly, aex-6 mutants exhibit the same defecation defect as aex
      3 mutants. aex-6; rab-3 double mutants have behavioral and pharmacological
      defects similar to aex-3 mutants. In addition, we demonstrate that RBF-1
      (rabphilin) is an effector of RAB-27. Therefore, our work demonstrates that AEX-3
      regulates both RAB-3 and RAB-27, that both RAB-3 and RAB-27 regulate synaptic
      transmission, and that RAB-27 potentially acts through its effector RBF-1 to
      promote soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE) function.

PMID- 16571674
TI  - Centromere targeting of the chromosomal passenger complex requires a ternary
      subcomplex of Borealin, Survivin, and the N-terminal domain of INCENP.
AB  - The chromosomal passenger complex (CPC), consisting of the serine/threonine
      kinase Aurora B, the inner centromere protein INCENP, Survivin, and
      Borealin/DasraB, has essential functions at the centromere in ensuring correct
      chromosome alignment and segregation. Despite observations that small interfering
      RNA-mediated knockdown of any one member of the CPC abolishes localization of the
      other subunits, it remains unclear how the complex is targeted to the centromere.
      We have now identified a ternary subcomplex of the CPC comprising Survivin,
      Borealin, and the N-terminal 58 amino acids of INCENP in vitro and in vivo. This
      subcomplex was found to be essential and sufficient for targeting to the
      centromere. Notably, Aurora B kinase, the enzymatic core of the CPC, was not
      required for centromere localization of the subcomplex. We demonstrate that CPC
      targeting to the centromere does not depend on CENP-A and hMis12, two core
      components for kinetochore/centromere assembly, and provide evidence that the CPC
      may be directed to centromeric DNA directly via the Borealin subunit. Our
      findings thus establish a functional module within the CPC that assembles on the
      N terminus of INCENP and controls centromere recruitment.

PMID- 16571675
TI  - Involvement of Akt in ER-to-Golgi transport of SCAP/SREBP: a link between a key
      cell proliferative pathway and membrane synthesis.
AB  - Akt is a critical regulator of cell growth, proliferation, and survival that is
      activated by phosphatidylinositol 3-kinase (PI3K). We investigated the effect of
      PI3K inhibition on activation of sterol regulatory element binding protein-2
      (SREBP-2), a master regulator of cholesterol homeostasis. SREBP-2 processing
      increased in response to various cholesterol depletion approaches (including
      statin treatment) and this increase was blunted by treatment with a potent and
      specific inhibitor of PI3K, LY294002, or when a plasmid encoding a dominant
      negative form of Akt (DN-Akt) was expressed. LY294002 also suppressed SREBP-2
      processing induced by insulin-like growth factor-1. Furthermore, LY294002
      treatment down-regulated SREBP-2 or -1c gene targets and decreased cholesterol
      and fatty acid synthesis. Fluorescence microscopy studies indicated that LY294002
      disrupts transport of the SREBP escort protein, SCAP, from the endoplasmic
      reticulum to the Golgi. This disruption was also shown by immunofluorescence
      staining when DN-Akt was expressed. Taken together, our studies indicate that the
      PI3K/Akt pathway is involved in SREBP-2 transport to the Golgi, contributing to
      the control of SREBP-2 activation. Our results provide a crucial mechanistic link
      between the SREBP and PI3K/Akt pathways that may be reconciled teleologically
      because synthesis of new membrane is an absolute requirement for cell growth and
      proliferation.

PMID- 16571676
TI  - The function and regulation of budding yeast Swe1 in response to interrupted DNA
      synthesis.
AB  - Periodically regulated cyclin-dependent kinase (Cdk) is required for DNA
      synthesis and mitosis. Hydroxyurea (HU) inhibits DNA synthesis by depleting
      dNTPs, the basic unit for DNA synthesis. HU treatment triggers the S-phase
      checkpoint, which arrests cells at S-phase, inhibits late origin firing and
      stabilizes replication forks. Using budding yeast as a model system, we found
      that Swe1, a negative regulator of Cdk, appears at S-phase and accumulates in HU
      treatment cells. Interestingly, this accumulation is not dependent on S-phase
      checkpoint. Deltahsl1, Deltahsl7, and cdc5-2 mutants, which have defects in Swe1
      degradation, show HU sensitivity because of high Swe1 protein levels. We further
      demonstrated that their HU sensitivity is not a result of DNA damage accumulation
      or incomplete DNA synthesis; instead the sensitivity is due to their dramatically
      delayed recovery from HU-induced S-phase arrest. Strikingly, our in vivo data
      indicate that Swe1 inhibits the kinase activity of Clb2-Cdk1, but not that of
      Clb5-Cdk1. Therefore, S-phase accumulated Swe1 prevents Clb2-Cdk1-mediated
      mitotic activities, but has little effects on Clb5-Cdk1-associated S-phase
      progression.

PMID- 16571677
TI  - A critical role for tetraspanin CD151 in alpha3beta1 and alpha6beta4 integrin
      dependent tumor cell functions on laminin-5.
AB  - The basement membrane protein laminin-5 supports tumor cell adhesion and motility
      and is implicated at multiple steps of the metastatic cascade. Tetraspanin CD151
      engages in lateral, cell surface complexes with both of the major laminin-5
      receptors, integrins alpha3beta1 and alpha6beta4. To determine the role of CD151
      in tumor cell responses to laminin-5, we used retroviral RNA interference to
      efficiently silence CD151 expression in epidermal carcinoma cells. Near total
      loss of CD151 had no effect on steady state cell surface expression of
      alpha3beta1, alpha6beta4, or other integrins with which CD151 associates.
      However, CD151-silenced carcinoma cells displayed markedly impaired motility on
      laminin-5, accompanied by unusually persistent lateral and trailing edge adhesive
      contacts. CD151 silencing disrupted alpha3beta1 integrin association with
      tetraspanin-enriched microdomains, reduced the bulk detergent extractability of
      alpha3beta1, and impaired alpha3beta1 internalization in cells migrating on
      laminin-5. Both alpha3beta1- and alpha6beta4-dependent cell adhesion to laminin-5
      were also impaired in CD151-silenced cells. Reexpressing CD151 in CD151-silenced
      cells reversed the adhesion and motility defects. Finally, loss of CD151 also
      impaired migration but not adhesion on substrates other than laminin-5. These
      data show that CD151 plays a critical role in tumor cell responses to laminin-5
      and reveal promotion of integrin recycling as a novel potential mechanism whereby
      CD151 regulates tumor cell migration.

PMID- 16571678
TI  - Cdc42p GDP/GTP cycling is necessary for efficient cell fusion during yeast
      mating.
AB  - The highly conserved small Rho G-protein, Cdc42p plays a critical role in cell
      polarity and cytoskeleton organization in all eukaryotes. In the yeast
      Saccharomyces cerevisiae, Cdc42p is important for cell polarity establishment,
      septin ring assembly, and pheromone-dependent MAP-kinase signaling during the
      yeast mating process. In this study, we further investigated the role of Cdc42p
      in the mating process by screening for specific mating defective cdc42 alleles.
      We have identified and characterized novel mating defective cdc42 alleles that
      are unaffected in vegetative cell polarity. Replacement of the Cdc42p Val36
      residue with Met resulted in a specific cell fusion defect. This cdc42[V36M]
      mutant responded to mating pheromone but was defective in cell fusion and in
      localization of the cell fusion protein Fus1p, similar to a previously isolated
      cdc24 (cdc24-m6) mutant. Overexpression of a fast cycling Cdc42p mutant
      suppressed the cdc24-m6 fusion defect and conversely, overexpression of Cdc24p
      suppressed the cdc42[V36M] fusion defect. Taken together, our results indicate
      that Cdc42p GDP-GTP cycling is critical for efficient cell fusion.

PMID- 16571679
TI  - RINT-1 regulates the localization and entry of ZW10 to the syntaxin 18 complex.
AB  - RINT-1 was first identified as a Rad50-interacting protein that participates in
      radiation-induced G2/M checkpoint control. We have recently reported that RINT-1,
      together with the dynamitin-interacting protein ZW10 and others, is associated
      with syntaxin 18, an endoplasmic reticulum (ER)-localized SNARE involved in
      membrane trafficking between the ER and Golgi. To address the role of RINT-1 in
      membrane trafficking, we examined the effects of overexpression and knockdown of
      RINT-1 on Golgi morphology and protein transport from the ER. Overexpression of
      the N-terminal region of RINT-1, which is responsible for the interaction with
      ZW10, caused redistribution of ZW10. Concomitantly, ER-to-Golgi transport was
      blocked and the Golgi was dispersed. Knockdown of RINT-1 also disrupted membrane
      trafficking between the ER and Golgi. Notably, silencing of RINT-1 resulted in a
      reduction in the amount of ZW10 associated with syntaxin 18, concomitant with
      ZW10 redistribution. In contrast, no redistribution or release of RINT-1 from the
      syntaxin 18 complex was observed when ZW10 expression was reduced. These results
      taken together suggest that RINT-1 coordinates the localization and function of
      ZW10 by serving as a link between ZW10 and the SNARE complex comprising syntaxin
      18.

PMID- 16571680
TI  - SMAP2, a novel ARF GTPase-activating protein, interacts with clathrin and
      clathrin assembly protein and functions on the AP-1-positive early endosome/trans
      Golgi network.
AB  - We recently reported that SMAP1, a GTPase-activating protein (GAP) for Arf6,
      directly interacts with clathrin and regulates the clathrin-dependent endocytosis
      of transferrin receptors from the plasma membrane. Here, we identified a SMAP1
      homologue that we named SMAP2. Like SMAP1, SMAP2 exhibits GAP activity and
      interacts with clathrin heavy chain (CHC). Furthermore, we show that SMAP2
      interacts with the clathrin assembly protein CALM. Unlike SMAP1, however, SMAP2
      appears to be a regulator of Arf1 in vivo, because cells transfected with a GAP
      negative SMAP2 mutant were resistant to brefeldin A. SMAP2 colocalized with the
      adaptor proteins for clathrin AP-1 and EpsinR on the early endosomes/trans-Golgi
      network (TGN). Moreover, overexpression of SMAP2 delayed the accumulation of
      TGN38/46 molecule on the TGN. This suggests that SMAP2 functions in the
      retrograde, early endosome-to-TGN pathway in a clathrin- and AP-1-dependent
      manner. Thus, the SMAP gene family constitutes an important ArfGAP subfamily,
      with each SMAP member exerting both common and distinct functions in vesicle
      trafficking.

PMID- 16571681
TI  - The regulation of microtubule dynamics in Saccharomyces cerevisiae by three
      interacting plus-end tracking proteins.
AB  - Microtubule plus-end tracking proteins (+TIPs) are a diverse group of molecules
      that regulate microtubule dynamics and interactions of microtubules with other
      cellular structures. Many +TIPs have affinity for each other but the functional
      significance of these associations is unclear. Here we investigate the physical
      and functional interactions among three +TIPs in S. cerevisiae, Stu2, Bik1, and
      Bim1. Two-hybrid, coimmunoprecipitation, and in vitro binding assays demonstrate
      that they associate in all pairwise combinations, although the interaction
      between Stu2 and Bim1 may be indirect. Three-hybrid assays indicate that these
      proteins compete for binding to each other. Thus, Stu2, Bik1, and Bim1 interact
      physically but do not appear to be arranged in a single unique complex. We
      examined the functional interactions among pairs of proteins by comparing
      cytoplasmic and spindle microtubule dynamics in cells lacking either one or both
      proteins. On cytoplasmic microtubules, Stu2 and Bim1 act cooperatively to
      regulate dynamics in G1 but not in preanaphase, whereas Bik1 acts independently
      from Stu2 and Bim1. On kinetochore microtubules, Bik1 and Bim1 are redundant for
      regulating dynamics, whereas Stu2 acts independently from Bik1 and Bim1. These
      results indicate that interactions among +TIPS can play important roles in the
      regulation of microtubule dynamics.

PMID- 16571682
TI  - Dorothy Reed Mendenhall (1874-1964).

PMID- 16571684
TI  - False claims in tobacco litigation junk science article.

PMID- 16571685
TI  - The trouble with MSM.

PMID- 16571686
TI  - Experiences of hurricane Katrina evacuees in Houston shelters: implications for
      future planning.
AB  - OBJECTIVES: To shed light on how the public health community can promote the
      recovery of Hurricane Katrina victims and protect people in future disasters, we
      examined the experiences of evacuees housed in Houston area shelters 2 weeks
      after the hurricane. METHODS: A survey was conducted September 10 through 12,
      2005, with 680 randomly selected respondents who were evacuated to Houston from
      the Gulf Coast as a result of Hurricane Katrina. Interviews were conducted in Red
      Cross shelters in the greater Houston area. RESULTS: Many evacuees suffered
      physical and emotional stress during the storm and its aftermath, including going
      without adequate food and water. In comparison with New Orleans and Louisiana
      residents overall, disproportionate numbers of this group were African American,
      had low incomes, and had no health insurance coverage. Many had chronic health
      conditions and relied heavily on the New Orleans public hospital system, which
      was destroyed in the storm. CONCLUSIONS: Our results highlight the need for
      better plans for emergency communication and evacuation of low-income and
      disabled citizens in future disasters and shed light on choices facing
      policymakers in planning for the long-term health care needs of vulnerable
      populations.

PMID- 16571687
TI  - Examining the course of homelessness: right direction, wrong approach.

PMID- 16571688
TI  - The importance of both sexual behavior and identity.

PMID- 16571689
TI  - Life-course socioeconomic position and hypertension in African American men: the
      Pitt County Study.
AB  - OBJECTIVES: We investigated the odds of hypertension for Black men in
      relationship to their socioeconomic position (SEP) in both childhood and
      adulthood. METHODS: On the basis of their parents' occupation, we classified 379
      men in the Pitt County (North Carolina) Study into low and high childhood SEP.
      The men's own education, occupation, employment status, and home ownership status
      were used to classify them into low and high adulthood SEP. Four life-course SEP
      categories resulted: low childhood/low adulthood, low childhood/high adulthood,
      high childhood/low adulthood, and high childhood/high adulthood. RESULTS: Low
      childhood SEP was associated with a 60% greater odds of hypertension, and low
      adulthood SEP was associated with a 2-fold greater odds of hypertension. Compared
      with men of high SEP in both childhood and adulthood, the odds of hypertension
      were 7 times greater for low/low SEP men, 4 times greater for low/high SEP men,
      and 6 times greater for high/low SEP men. CONCLUSIONS: Greater access to material
      resources in both childhood and adulthood was protective against premature
      hypertension in this cohort of Black men. Though some parameter estimates were
      imprecise, study findings are consistent with both pathway and cumulative burden
      models of hypertension.

PMID- 16571690
TI  - Patient privacy and conflicting legal and ethical obligations in El Salvador:
      reporting of unlawful abortions.
AB  - Postabortion care providers who breach patient confidentiality endanger women's
      health and violate ethics. A 1998 abortion ban in El Salvador likely spurred an
      increase in the number of women investigated, because many women were reported to
      legal authorities by health care providers. Having analyzed safeguards of
      confidentiality in laws and ethical guidelines, we obtained information from
      legal records on women prosecuted from 1998 to 2003 and identified factors that
      may lead to reporting through a survey of obstetrician-gynecologists (n=110).
      Although ethical and human rights standards oblige providers to respect patients'
      privacy, 80% of obstetrician-gynecologists mistakenly believed reporting was
      required. Most respondents (86%) knew that women delay seeking care because of
      fear of prosecution, yet a majority (56%) participated in notification of legal
      authorities.

PMID- 16571691
TI  - Newborn screening: complexities in universal genetic testing.
AB  - Newborn screening (NBS)--in which each newborn infant is screened for up to 50
      specific metabolic disorders for early detection and intervention--is the first
      program of populationwide genetic testing. As a public health intervention, NBS
      has greatly improved the lives of thousands of affected children. New
      technologies and new economic and social forces pose significant ethical and
      clinical challenges to NBS. Two primary challenges concern (1) accommodating
      clinical and ethical standards to rapid technological developments in NBS and (2)
      preparing public health systems to respond to the medical advances and social
      forces driving expansion of NBS programs. We describe and analyze these
      challenges through consideration of 3 disorders: phenylketonuria, medium-chain
      acyl-CoA dehydrogenase deficiency, and cystic fibrosis.

PMID- 16571692
TI  - Immunization initiation among infants in the Oregon Health Plan.
AB  - Infants who start receiving immunizations on time are more likely to be up to
      date at age 2 years. Among 39708 infants aged 3 months covered by the Oregon
      Health Plan (expanded Medicaid), those who did not have health care coverage
      within the first month of life were less likely to start receiving immunizations
      on time. Also at risk were infants in foster care, in subadoptive care, who were
      blind or disabled, who were Native American or Black, or whose mothers were not
      covered by the Oregon Health Plan.

PMID- 16571694
TI  - Barriers to participation in the food stamp program among food pantry clients in
      Los Angeles.
AB  - Substantial numbers of food pantry clients are eligible for food stamps but do
      not receive them. Background characteristics of 14317 food pantry users in Los
      Angeles were analyzed to provide information helpful in food stamp outreach
      programs. Ninety percent of food pantry users were living well below poverty
      level, 59% were Hispanic, and 44% were homeless. Only 15% of the food pantry
      clients received food stamps, with homelessness and limited English language
      skills acting as barriers to food stamp program participation.

PMID- 16571693
TI  - Fertility regulation and reproductive health in the Millennium Development Goals:
      the search for a perfect indicator.
AB  - Although several key elements of sexual and reproductive health are included in
      the United Nations Millennium Development Goals, a measure of women's capacity to
      regulate their fertility safely and effectively is missing. We considered the
      usefulness of 3 pairs of indicators in monitoring this component of reproductive
      health: contraceptive prevalence and total fertility; unmet need for
      contraception and unplanned births; and unsafe abortion and abortion mortality. A
      single measure of contraceptive use is insufficient. The risks women face from
      unplanned births and unsafe abortion should also be incorporated into the
      monitoring process, either directly within the Millennium Development Goals
      framework or as a parallel effort by reporting governments and other agencies.

PMID- 16571695
TI  - The associations between victimization, feeling unsafe, and asthma episodes among
      US high-school students.
AB  - We examined the associations between victimization, missed school because of
      feeling unsafe, and asthma episodes among US high-school students using the 2003
      Youth Risk Behavior Survey. Cross-sectional analyses on adolescents with asthma
      (n=1943) showed that any victimization and missed school because of feeling
      unsafe significantly increased the odds of having an asthma episode in the past
      year (adjusted odds ratio [OR]=1.45; 95% confidence interval [CI] = 1.07, 1.95
      and adjusted OR = 2.93; 95% CI = 1.90, 4.53, respectively). Victimization and
      feeling unsafe are important but poorly understood risk factors for asthma.

PMID- 16571696
TI  - Paternal age as a risk factor for low birthweight.
AB  - OBJECTIVES: We examined associations between paternal age and low birth-weight in
      the US urban population. METHODS: Using a population-based sample of 4621 births,
      we used multiple logistic regression analysis to estimate associations between
      paternal age and low birthweight, controlling for maternal age, other demographic
      factors, and the child's gender. RESULTS: When the child's gender and the
      mother's race/ethnicity, birthplace, parity, marital status, and health insurance
      type were controlled, teenaged fathers were 20% less likely and fathers older
      than 34 years were 90% more likely than fathers aged 20 to 34 years to have low
      birthweight babies. The associations were significant when maternal age was also
      controlled. No racial/ethnic differences in associations between paternal age and
      low birthweight were found. CONCLUSIONS: We identified paternal age as an
      independent risk factor for low birthweight in the US urban population,
      suggesting that more attention needs to be paid to paternal influences on birth
      outcomes and to the interactive effects of urban environments and individual risk
      factors on health.

PMID- 16571697
TI  - Justice and fairness in the Kennedy Krieger Institute lead paint study: the
      ethics of public health research on less expensive, less effective interventions.
AB  - The Kennedy Krieger lead paint study stirred controversial questions about
      whether research designed to develop less expensive interventions that are not as
      effective as existing treatments can be ethically warranted. Critics questioned
      the social value of such research and alleged that it sanctions a double
      standard, exploits participants, and is complicit in perpetuating the social
      injustice. In response, we demonstrate the propriety of conducting research on
      interventions that can be extended to the population in need by stipulating the
      limited conditions in which it is ethically warranted and providing fair terms of
      participation. We contend that the failure to conduct such research causes
      greater harm, because it deprives disadvantaged populations of the benefits of
      imminent incremental improvements in their health conditions.

PMID- 16571698
TI  - Improving birth control service utilization by offering services prerelease vs
      postincarceration.
AB  - OBJECTIVES: We examined whether incarcerated women would substantially increase
      birth control initiation if contraceptive services were available within the
      prison compared with after their release back into the community. METHODS: During
      phase 1 of the study, a nurse educator met with women at the Rhode Island Adult
      Correctional Institute and offered them referrals for contraceptive services at a
      community health clinic after their release. During phase 2, contraceptive
      services were offered to women during their incarceration. RESULTS: The majority
      of the participants (77.5%) reported a desire to initiate use of birth control
      methods. Within 4 weeks of their release, 4.4% of phase 1 participants initiated
      use of a contraceptive method, compared with 39.1% of phase 2 participants (odds
      ratio [OR]=14.6; 95% confidence interval [CI]=5.5, 38.8). CONCLUSIONS: Provision
      of contraceptive services to women during their incarceration is feasible and
      greatly increases birth control initiation compared to providing services only in
      the community.

PMID- 16571699
TI  - Trends in smokeless tobacco use among adults and adolescents in the United
      States.
AB  - OBJECTIVES: Smokeless tobacco has many adverse health effects. We analyzed long
      term national trends in smokeless tobacco use. METHODS: We used 1987 to 2000
      National Health Interview Survey data for adults aged 18 years and older, 1986 to
      2003 data from Monitoring the Future surveys of adolescents, and 1991 to 2003
      data from the Youth Risk Behavior Survey for 9th- to 12th-grade students to
      examine overall and demographic-specific trends. RESULTS: Smokeless tobacco use
      among adult and adolescent females was low and showed little change. Smokeless
      tobacco use among men declined slowly (relative decline=26%), with the largest
      declines among those aged 18 to 24 years or 65 years and older, Blacks, residents
      of the South, and persons in more rural areas. Overall and demographic-specific
      data for adolescent boys indicate that smokeless tobacco use increased for 12th
      grade students from 1986 until the early 1990s, but has subsequently declined
      rapidly in all grades since then (range of relative overall declines=43% to 48%).
      CONCLUSIONS: Smokeless tobacco use has declined sharply, especially among
      adolescent boys. Ongoing prevention and cessation efforts are needed to continue
      this trend.

PMID- 16571700
TI  - Research recruitment through US central cancer registries: balancing privacy and
      scientific issues.
AB  - Cancer registries are a valuable resource for recruiting participants for public
      health-oriented research, although such recruitment raises potentially competing
      concerns about patient privacy and participant accrual. We surveyed US central
      cancer registries about their policies for research contact with patients, and
      results showed substantial variation. The strategy used most frequently (37.5% of
      those that allowed patient contact), which was among the least restrictive, was
      for investigators to notify patients' physicians and then contact patients with
      an opt-out approach. The most restrictive strategy was for registry staff to
      obtain physician permission and contact patients with an opt-in approach.
      Population-based studies enhance cancer control efforts, and registry policies
      can affect researchers' ability to conduct such studies. Further discussion about
      balanced recruitment approaches that protect patient privacy and encourage
      beneficial research is needed.

PMID- 16571701
TI  - Reproductive health care and family planning needs among incarcerated women.
AB  - OBJECTIVES: Women in correctional institutions have substantial reproductive
      health problems, yet they are underserved in receipt of reproductive health care.
      We assessed the level of risk for sexually transmitted diseases (STDs) and the
      reproductive health needs of 484 incarcerated women in Rhode Island to plan an
      intervention for women returning to the community. METHODS: We used a 45-minute
      survey to assess medical histories, pregnancy and birth control use histories,
      current pregnancy intentions, substance use during the past 3 months, histories
      of childhood sexual abuse, and health attitudes and behaviors. RESULTS:
      Participants had extremely high risks for STDs and pregnancy, which was
      characterized by inconsistent birth control (66.5%) and condom use (80.4%),
      multiple partners (38%), and a high prevalence of unplanned pregnancies (83.6%)
      and STDs (49%). Only 15.4% said it was not likely that they would have sexual
      relations with a man within 6 months after release. CONCLUSION: Reproductive
      health services must be offered to incarcerated women. Such interventions will
      benefit the women, the criminal justice systems, and the communities to which the
      women will return.

PMID- 16571702
TI  - The mortality divide in India: the differential contributions of gender, caste,
      and standard of living across the life course.
AB  - OBJECTIVES: We investigated the contributions of gender, caste, and standard of
      living to inequalities in mortality across the life course in India. METHODS: We
      conducted a multilevel cross-sectional analysis of individual mortality, using
      the 1998-1999 Indian National Family Health Survey data for 529321 individuals
      from 26 states. RESULTS: Substantial mortality differentials were observed
      between the lowest and highest standard-of-living quintiles across all age
      groups, ranging from an odds ratio (OR) of 4.61 (95% confidence interval
      [CI]=2.98, 7.13) in the age group 2 to 5 years to an OR of 1.97 (95% CI=1.68,
      2.32) in the age group 45 to 64 years. Excess mortality for girls was evident
      only for the age group 2 to 5 years (OR=1.33, 95% CI=1.13, 1.58). Substantial
      caste differentials were observed at the beginning and end stages of life. Area
      variation in mortality is partially a result of the compositional effects of
      household standard of living and caste. CONCLUSIONS: The mortality burden, across
      the life course in India, falls disproportionately on economically disadvantaged
      and lower-caste groups. Residual state-level variation in mortality suggests an
      underlying ecology to the mortality divide in India.

PMID- 16571703
TI  - Service uptake and characteristics of injection drug users utilizing North
      America's first medically supervised safer injecting facility.
AB  - In 2003, the city of Vancouver, British Columbia, opened North America's first
      government-sanctioned safer injecting facility, where injection drug users (IDUs)
      can inject preobtained illicit drugs under the supervision of nurses. Use of the
      service by IDUs was followed by measurable reductions in public drug use and
      syringe sharing. IDUs who are frequently using the program tend to be high
      intensity cocaine and heroin injectors and homeless individuals. The facility has
      provided high-risk IDUs a hygienic space where syringe sharing can be eliminated
      and the risk of fatal overdose reduced. Ongoing evaluation will be required to
      assess its impact on overdose rates and HIV infection levels, as well as its
      ability to improve IDU contact with medical care and addiction treatment.

PMID- 16571704
TI  - Perceived neighborhood problems and quality of life, physical functioning, and
      depressive symptoms among adults with asthma.
AB  - OBJECTIVES: We investigated associations between perceived neighborhood problems
      and quality of life (QOL), physical functioning, and depressive symptoms among
      adults with asthma. METHODS: Using cross-sectional data from adults with asthma
      in northern California (n=435), we examined associations between 5 types of
      perceived neighborhood problems (traffic, noise, trash, smells, and fires) and
      asthma-specific QOL (Marks instrument), physical functioning (Short Form-12
      physical component summary), and depressive symptoms (Center for Epidemiological
      Studies-Depression). We used multivariate regression analysis. RESULTS: When
      asthma severity and sociodemographics were taken into account, people reporting a
      score of 8 or higher on a scale of 0 to 25 for serious problems (the top quartile
      of seriousness) in their neighborhoods had significantly poorer QOL scores (mean
      difference=5.91; standard error [SE]=1.63), poorer physical functioning (mean
      difference=-3.04; SE=1.27), and almost a fivefold increase in depressive symptoms
      (odds ratio=4.79; 95% confidence interval=2.41, 9.52). CONCLUSIONS: A high level
      of perceived neighborhood problems was associated with poorer QOL, poorer
      physical functioning, and increased depressive symptoms among people with asthma
      when disease severity and sociodemographic factors were taken into account.

PMID- 16571705
TI  - Exposure to the World Trade Center attack and the use of cigarettes and alcohol
      among New York City public high-school students.
AB  - We examined exposure to the World Trade Center attack and changes in cigarette
      smoking and drinking among 2731 New York City public high-school students
      evaluated 6 months after the attack. Increased drinking was associated with
      direct exposure to the World Trade Center attack (P < .05). Increased smoking was
      not directly associated with exposure to the World Trade Center attack but was
      marginally significantly associated with posttraumatic stress disorder (P= .06).
      Our findings suggest that targeted substance-use interventions for youths may be
      warranted after large-scale disasters.

PMID- 16571706
TI  - Work activity in pregnancy, preventive measures, and the risk of delivering a
      small-for-gestational-age infant.
AB  - OBJECTIVES: We undertook a case-control study to evaluate whether some
      occupational conditions during pregnancy increase the risk of delivering a small
      for-gestational-age (SGA) infant and whether taking measures to eliminate these
      conditions decreases that risk. METHODS: The 1536 cases and 4441 controls were
      selected from 43898 women who had single live births between January 1997 and
      March 1999 in Quebec, Canada. The women were interviewed by telephone after
      delivery. RESULTS: The risk of having an SGA infant increased with an irregular
      or shift-work schedule alone and with a cumulative index of the following
      occupational conditions: night hours, irregular or shift-work schedule, standing,
      lifting loads, noise, and high psychological demand combined with low social
      support. When the conditions were not eliminated, the risk increased with the
      number of conditions (P(trend) =.004; odds ratios=1.00, 1.08, 1.28, 1.43, and
      2.29 for 0, 1, 2, 3, and 4-6 conditions, respectively). Elimination of the
      conditions before 24 weeks of pregnancy brought the risks close to those of
      unexposed women. CONCLUSIONS: Certain occupational conditions experienced by
      pregnant women can increase their risk of having an SGA infant, but preventive
      measures can reduce the risk.

PMID- 16571707
TI  - Telephone coverage and health survey estimates: evaluating the need for concern
      about wireless substitution.
AB  - OBJECTIVES: We sought to determine whether the exclusion of adults without
      landline telephones may bias estimates derived from health-related telephone
      surveys. METHODS: We took data from the 2004 and 2005 National Health Interview
      Survey and used logistic regression to compare the odds of behavioral risk
      factors and health care service use for adults with landline telephones to those
      for adults with only wireless telephones and adults without any telephone
      service. RESULTS: When interviewed, 7.2% of adults, including those who did and
      did not have wireless telephones, did not have landline telephones. Relative to
      adults with landline telephones, adults without landline telephones had greater
      odds of smoking and being uninsured, and they had lower odds of having diabetes,
      having a usual place for medical care, and having received an influenza
      vaccination in the past year. CONCLUSIONS: As people substitute wireless
      telephones for landline telephones, the percentage of adults without landline
      telephones has increased significantly but is still low, which minimizes the bias
      resulting from their exclusion from telephone surveys. Bias greater than 1
      percentage point is expected only for estimates of health insurance, smoking,
      binge drinking, having a usual place for care, and receiving an influenza
      vaccination.

PMID- 16571708
TI  - Fostering international collaboration in birth defects research and prevention: a
      perspective from the International Clearinghouse for Birth Defects Surveillance
      and Research.
AB  - The International Clearing-house for Birth Defects Surveillance and Research,
      formerly known as International Clearinghouse of Birth Defects Monitoring
      Systems, consists of 40 registries worldwide that collaborate in monitoring 40
      types of birth defects. Clearinghouse activities include the sharing and joint
      monitoring of birth defect data, epidemiologic and public health research, and
      capacity building, with the goal of reducing disease and promoting healthy birth
      outcomes through primary prevention.We discuss 3 of these activities: the
      collaborative assessment of the potential teratogenicity of first-trimester use
      of medications (the MADRE project), an example of the intersection of
      surveillance and research; the international databases of people with orofacial
      clefts, an example of the evolution from surveillance to outcome research; and
      the study of genetic polymorphisms, an example of collaboration in public health
      genetics.

PMID- 16571709
TI  - Antismoking advertisements for youths: an independent evaluation of health,
      counter-industry, and industry approaches.
AB  - OBJECTIVES: We used a validated copy test method to examine the effectiveness of
      8 types of antismoking advertisements representing health, counterindustry, and
      industry approaches. We tested the hypothesis that health ads about tobacco
      victims can lower most adolescents' intent to smoke if the ads elicit disgust and
      anti-industry feelings rather than fear. We hypothesized null effects for
      adolescents with conduct disorder because of their abnormally low empathy.
      METHODS: Ninth-grade students from 8 California public schools (n=1725) were
      randomly assigned to view 1 of 9 videotapes containing a TV show with ads that
      included either a set of antismoking ads or a set of control ads. Participants
      completed baseline measures assessing personality traits and postexposure
      measures assessing smoking intent, feelings, beliefs, and ad evaluations.
      RESULTS: Ads focusing on young victims suffering from serious tobacco-related
      diseases elicited disgust, enhanced anti-industry motivation, and reduced intent
      to smoke among all but conduct-disordered adolescents. Counterindustry and
      industry ads did not significantly lower smoking intention. CONCLUSIONS: Sponsors
      of tobacco use prevention ad campaigns should consider using ads showing tobacco
      related disease and suffering, not just counterindustry ads. Ads should be copy
      tested before airing.

PMID- 16571710
TI  - Outcomes of drug and alcohol treatment programs among American Indians in
      California.
AB  - OBJECTIVES: We examined differences in substance abuse treatment outcomes between
      American Indians and their non-American Indian counterparts in California, during
      2000 to 2002. METHODS: A total of 368 American Indians and a matched sample of
      368 non-American Indians from 39 substance abuse treatment programs in 13
      California counties were assessed at multiple time points. Records on arrests,
      driving while under the influence of alcohol or drugs, and mental health care
      were obtained 1 year before and 1 year after treatment entry. Differences in
      pretreatment characteristics, services received, treatment satisfaction,
      treatment completion and retention, and outcomes were examined. RESULTS:
      Pretreatment problems were similarly severe among American Indians and non
      American Indians. About half in both groups either completed treatment or stayed
      in treatment more than 90 days; American Indians in residential care had
      significantly shorter treatment retention. American Indians received fewer
      individual sessions and out-of-program services, especially for alcohol abuse,
      but were nevertheless generally satisfied with their treatment. Both groups
      improved after treatment, with American Indians demonstrating greater reductions
      in arrests than non-American Indians. CONCLUSION: American Indians benefit from
      substance abuse treatment programs, although the type and intensity of services
      offered could be improved.

PMID- 16571711
TI  - A nationwide population-based study identifying health disparities between
      American Indians/Alaska Natives and the general populations living in select
      urban counties.
AB  - OBJECTIVES: Despite their increasing numbers, little is known about the health of
      American Indians/Alaska Natives living in urban areas. We examined the health
      status of American Indian/Alaska Native populations served by 34 federally funded
      urban Indian health organizations. METHODS: We analyzed US census data and vital
      statistics data for the period 1990 to 2000. RESULTS: Disparities were revealed
      in socioeconomic, maternal and child health, and mortality indicators between
      American Indians/Alaska Natives and the general populations in urban Indian
      health organization service areas and nationwide. American Indians/Alaska Natives
      were approximately twice as likely as these general populations to be poor, to be
      unemployed, and to not have a college degree. Similar differences were observed
      in births among mothers who received late or no prenatal care or consumed alcohol
      and in mortality attributed to sudden infant death syndrome, chronic liver
      disease, and alcohol consumption. CONCLUSIONS: We found health disparities
      between American Indians/Alaska Natives and the general populations living in
      selected urban areas and nationwide. Such disparities can be addressed through
      improvements in health care access, high-quality data collection, and policy
      initiatives designed to provide sufficient resources and a more unified vision of
      the health of urban American Indians/Alaska Natives.

PMID- 16571712
TI  - Maternal risk profiles and the primary cesarean rate in the United States, 1991
      2002.
AB  - OBJECTIVES: We examined factors contributing to shifts in primary cesarean rates
      in the United States between 1991 and 2002. METHODS: US national birth
      certificate data were used to assess changes in primary cesarean rates stratified
      according to maternal age, parity, and race/ethnicity. Trends in the occurrence
      of medical risk factors or complications of labor or delivery listed on birth
      certificates and the corresponding primary cesarean rates for such conditions
      were examined. RESULTS: More than half (53%) of the recent increase in overall
      cesarean rates resulted from rising primary cesarean rates. There was a steady
      decrease in the primary cesarean rate from 1991 to 1996, followed by a rapid
      increase from 1996 to 2002. In 2002, more than one fourth of first-time mothers
      delivered their infants via cesarean. Changing primary cesarean rates were not
      related to general shifts in mothers' medical risk profiles. However, rates for
      virtually every condition listed on birth certificates shifted in the same
      pattern as with the overall rates. CONCLUSIONS: Our results showed that shifts in
      primary cesarean rates during the study period were not related to shifts in
      maternal risk profiles.

PMID- 16571713
TI  - Asthma prevalence among US adults, 1998-2000: role of Puerto Rican ethnicity and
      behavioral and geographic factors.
AB  - OBJECTIVES: We analyzed asthma prevalence among US adults by age, gender, race,
      Puerto Rican ethnicity, and other demographic, behavioral, health, and geographic
      variables. We hypothesized that high prevalences would be observed among Puerto
      Ricans and in the Northeast census region. METHODS: We used data from the 1998
      through 2000 US National Health Interview Surveys. Information on lifetime
      history of asthma and asthma in the past year was collected from 95615 adults. We
      calculated weighted prevalence estimates and odds ratios from logistic
      regression. RESULTS: Of US adults, 8.9% had ever been diagnosed with asthma, and
      3.4% had experienced an episode in the past 12 months. Asthma diagnosis rates
      were highest among Puerto Ricans (17.0%) and lowest among Mexican Americans
      (3.9%); rates were 9.6% and 9.2% among non-Hispanic Blacks and non-Hispanic
      Whites, respectively. Geographically, asthma prevalence was highest in the West
      (10.5%) and lowest in the Northeast (8.6%). Puerto Ricans in all regions had high
      asthma rates. CONCLUSIONS: final logistic regression model included
      race/ethnicity, obesity, poverty, female gender, and cigarette smoking. Higher
      asthma rates were confirmed among Puerto Ricans but not in the Northeast region.

PMID- 16571714
TI  - Bridging disparity: a multidisciplinary approach for influenza vaccination in an
      American Indian community.
AB  - OBJECTIVES: The Whiteriver Service Unit (WRSU) used proven effective methods to
      conduct an influenza vaccination campaign during the 2002-2003 influenza season
      to bridge the vaccination gap between American Indians and Alaska Natives and the
      US population as a whole. METHODS: In our vaccination program, we used a
      multidisciplinary approach that included staff and community education, standing
      orders, vaccination of hospitalized patients, and employee, outpatient,
      community, and home vaccinations without financial barriers. RESULTS: WRSU
      influenza vaccination coverage rates among persons aged 65 years and older, those
      aged 50 to 64 years, and those with diabetes were 71.8%, 49.6%, and 70.2%,
      respectively, during the 2002-2003 influenza season. We administered most
      vaccinations to persons aged 65 years and older through the outpatient clinics
      (63.6%) and public health nurses (30.0%). The WRSU employee influenza vaccination
      rate was 72.8%. CONCLUSIONS: We achieved influenza vaccination rates in targeted
      groups of an American Indian population that are comparable to or higher than
      rates in other US populations. Our system may be a useful model for other
      facilities attempting to bridge disparity for influenza vaccination.

PMID- 16571715
TI  - Patient preferences and adherence to colorectal cancer screening in an urban
      population.
AB  - We measured patient preferences for colorectal cancer (CRC) screening strategies
      and actual receipt of alternative CRC screening tests among an urban minority
      sample participating in an intervention study. The fecal occult blood test was
      the most preferred test, reportedly owing to its convenience and the noninvasive
      nature. For individuals who obtained a test that was other than their stated
      preference (41.1%), reasons for this discordance may be due to physician
      preferences that override patient preferences.

PMID- 16571716
TI  - Associations of maternal age- and parity-related factors with trends in low
      birthweight rates: United States, 1980 through 2000.
AB  - OBJECTIVES: We assessed the effects of changes in the maternal age-parity
      distribution and age-and parity-specific low-birthweight rates on low-birthweight
      trends in the United States. METHODS: We used natality file data from 1980
      through 2000 to assess very-low-birthweight and low-birthweight rates among
      singleton live-born infants. RESULTS: Changes in age-and parity-specific low
      birthweight rates were the main contributor to the overall trend in rates.
      However, changes in the age-parity distribution, primarily delayed childbearing,
      had a smaller but noticeable impact. The very-low-birthweight rate increased 27%
      among Black women, and changes in the age-parity distribution were associated
      with, on average, more than 20% of the increased rate during the 1990s. Among
      Hispanic and non-Hispanic White women, on average, more than 10% of the rate
      increase observed during the 1990s was associated with changes in the age-parity
      distribution. CONCLUSIONS: Assuming minimal changes in age-specific rates,
      delayed childbearing may play an increasingly important role in low-birthweight
      trends in the United States.

PMID- 16571717
TI  - The mental health of married, cohabiting, and non-coresident parents with
      infants.
AB  - OBJECTIVES: We compared recent parents (married, cohabiting, not cohabiting but
      romantically involved, and not romantically involved) to examine the association
      between mental health problems and relationship status. METHODS: We analyzed data
      from the Fragile Families and Child Wellbeing Study that followed a cohort of
      approximately 4900 births in large US cities. Our study included a large
      oversample of nonmarital births (n=3700) and interviews with both mothers and
      fathers. We used the Composite International Diagnostic Interview Short Form to
      assess depression and generalized anxiety 1 year after the birth. Self reports
      were used to measure heavy drinking, illicit drug use, incarceration, and partner
      violence. RESULTS: Unmarried parents reported more mental health and behavioral
      problems than did married parents, and unmarried parents whose relationships
      ended before the birth reported more impairment compared with other groups of
      unmarried parents. CONCLUSIONS: A substantial number of children are born to
      unmarried parents and are at risk for poor parenting and poor developmental
      outcomes. Government initiatives aimed at increasing marriage rates among low
      income couples need to consider the mental health status of unmarried parents.

PMID- 16571719
TI  - Quantitative analysis of in vivo initiator selection by yeast RNA polymerase II
      supports a scanning model.
AB  - Initiation of transcription by RNA polymerase II (RNAP II) on Saccharomyces
      cerevisiae messenger RNA (mRNA) genes typically occurs at multiple sites 40-120
      bp downstream of the TATA box. The mechanism that accommodates this extended and
      variable promoter architecture is unknown, but one model suggests that RNAP II
      forms an open promoter complex near the TATA box and then scans the template DNA
      strand for start sites. Unlike most protein-coding genes, small nuclear RNA gene
      transcription starts predominantly at a single position. We identify a highly
      efficient initiator element as the primary start site determinant for the yeast
      U4 small nuclear RNA gene, SNR14. Consistent with the scanning model,
      transcription of an SNR14 allele with tandemly duplicated start sites initiates
      primarily from the upstream site, yet the downstream site is recognized with
      equivalent efficiency by the diminished population of RNAP II molecules that
      encounter it. A quantitative in vivo assay revealed that SNR14 initiator
      efficiency is nearly perfect (approximately 90%), which explains the precision of
      U4 RNA 5' end formation. Initiator efficiency was reduced by cis-acting mutations
      at -8, -7, -1, and +1 and trans-acting substitutions in the TFIIB B-finger. These
      results expand our understanding of RNAP II initiation preferences and provide
      new support for the scanning model.

PMID- 16571718
TI  - Auto-activation of the apoptosis protein Bax increases mitochondrial membrane
      permeability and is inhibited by Bcl-2.
AB  - Interactions among Bcl-2 family proteins mediated by Bcl-2 homology (BH) regions
      transform apoptosis signals into actions. The interactions between BH3 region
      only proteins and multi-BH region proteins such as Bax and Bcl-2 have been
      proposed to be the dominant interactions required for initiating apoptosis.
      Experimental evidence also suggests that both homo- and hetero-interactions are
      mediated primarily by the BH3 regions in all Bcl-2 family proteins and contribute
      to commitment to or inhibition of apoptosis. We found that a peptide containing
      the BH3 helix of Bax was not sufficient to activate recombinant Bax to
      permeabilize mitochondria. However, an extended peptide containing the BH3 helix
      and additional downstream sequences activated Bax to permeabilize mitochondria
      and liposomes. Bcl-2 inhibited the membrane-permeabilizing activity of peptide
      activated Bax. This activity of Bcl-2 was inhibited by the extended but not the
      BH3-only peptide despite both peptides binding to Bcl-2 with similar affinity.
      Further, membrane-bound Bax activation intermediates directly activated soluble
      Bax further permeabilizing the membrane. Bcl-2 inhibited Bax auto-activation. We
      therefore propose that Bax auto-activation amplifies the initial death signal
      produced by BH3-only proteins and that Bcl-2 functions as an inhibitor of Bax
      auto-activation.

PMID- 16571720
TI  - A second nitrogenase-like enzyme for bacteriochlorophyll biosynthesis:
      reconstitution of chlorophyllide a reductase with purified X-protein (BchX) and
      YZ-protein (BchY-BchZ) from Rhodobacter capsulatus.
AB  - In most photosynthetic organisms, the chlorin ring structure of chlorophyll a is
      formed by the reduction of the porphyrin D-ring by the dark-operative nitrogenase
      like enzyme, protochlorophyllide reductase (DPOR). Subsequently, the chlorin B
      ring is reduced in bacteriochlorophyll biosynthesis to form a bacteriochlorin
      ring structure. Phenotypic analysis of mutants lacking one of three genes, bchX,
      bchY, or bchZ, which show significant sequence similarity to the structural genes
      of nitrogenase, suggests that a second nitrogenase-like enzyme is involved in the
      chlorin B-ring reduction. However, there is no biochemical evidence for this.
      Here, we report the reconstitution of chlorophyllide a reductase (COR) with
      purified proteins. Two Rhodobacter capsulatus strains that overexpressed Strep
      tagged BchX and BchY were isolated. Strep-tagged BchX was purified as a single
      polypeptide, and BchZ was co-purified with Strep-tagged BchY. When BchX and BchY
      BchZ components were incubated with chlorophyllide a, ATP, and dithionite under
      anaerobic conditions, chlorophyllide a was converted to a new pigment with a Qy
      band of longer wavelength at 734 nm (P734) in 80% acetone. The formation of P734
      was dependent on ATP and dithionite. High performance liquid chromatography and
      mass spectroscopic analysis indicated that P734 is 3-vinyl bacteriochlorophyllide
      a, which is formed by the B-ring reduction of chlorophyllide a. These results
      demonstrate that the B-ring of chlorin is reduced by a second nitrogenase-like
      enzyme and that the sequential actions of two nitrogenase-like enzymes, DPOR and
      COR, convert porphyrin to bacteriochlorin. The evolutionary implications of
      nitrogenase-like enzymes to determine the ring structure of (bacterio)chlorophyll
      pigments are discussed.

PMID- 16571721
TI  - MLDP, a novel PAT family protein localized to lipid droplets and enriched in the
      heart, is regulated by peroxisome proliferator-activated receptor alpha.
AB  - Cytosolic lipid droplets (LDs) are multifunctional organelles that exist in all
      types of eukaryotic cells and control lipid homeostasis. In mammalian cells LDs
      contain a class of proteins in their surface layers that share a homologous
      sequence called the PAT domain, including perilipin, adipose differentiation
      related protein (ADRP), a tail-interacting protein of 47 kDa (TIP47), and S3-12,
      which are distributed tissue- or cell type-selectively. Expression in some cases
      is regulated by peroxisome proliferator-activated receptors (PPARs). In this
      study we identified a new PAT family member named MLDP (myocardial LD protein) in
      a murine cDNA data base and showed the mRNA and protein to be highly enriched in
      the heart and also expressed at lower levels in the liver and adrenals. Upon
      subcellular fractionation, a substantial amount of MLDP was detected in the top
      fraction enriched with LDs. Furthermore, overexpressed MLDP tagged with green
      fluorescent protein accumulated at the surfaces of LDs and co-localized with
      perilipin and ADRP. Deletion analysis demonstrated the N-terminal region
      containing a PAT-1 domain and the following 33-mer domain to be required for
      targeting of MLDP to LDs. MLDP was found to be up-regulated at both mRNA and
      protein levels in the heart and liver by a selective ligand for PPARalpha,
      Wy14,643, but not in PPARalpha knock-out mice. MLDP expression was also increased
      upon fasting in parallel with ADRP. These results indicate that MLDP is a bona
      fide new PAT family member localized in LDs. Its expression depends on the
      physiological conditions and the action of PPARalpha.

PMID- 16571722
TI  - Direct interaction of the molecular scaffolds POSH and JIP is required for
      apoptotic activation of JNKs.
AB  - A sequential pathway (the JNK pathway) that includes activation of Rac1/Cdc42,
      mixed lineage kinases, MAP kinase kinases 4 and 7, and JNKs plays a required role
      in many paradigms of apoptotic cell death. However, the means by which this
      pathway is assembled and directed toward apoptotic death has been unclear. Here,
      we report that propagation of the apoptotic JNK pathway requires the cooperative
      interaction of two molecular scaffolds, POSH and JIPs. POSH (plenty of SH3s) is a
      multidomain GTP-Rac1-interacting protein that binds and promotes activation of
      mixed lineage kinases. JIPs are reported to bind MAP kinase kinases 4/7 and JNKs.
      We find that POSH and JIPs directly associate with one another to form a
      multiprotein complex, PJAC (POSH-JIP apoptotic complex), that includes all of the
      known kinase components of the pathway. Our observations indicate that this
      complex is required for JNK activation and cell death in response to apoptotic
      stimuli.

PMID- 16571723
TI  - A role for AQP5 in activation of TRPV4 by hypotonicity: concerted involvement of
      AQP5 and TRPV4 in regulation of cell volume recovery.
AB  - Regulation of cell volume in response to changes in osmolarity is critical for
      cell function and survival. However, the molecular basis of osmosensation and
      regulation of cell volume are not clearly understood. We have examined the
      mechanism of regulatory volume decrease (RVD) in salivary gland cells and report
      a novel association between osmosensing TRPV4 (transient receptor potential
      vanalloid 4) and AQP5 (aquaporin 5), which is required for regulating water
      permeability and cell volume. Exposure of salivary gland cells and acini to
      hypotonicity elicited an increase in cell volume and activation of RVD.
      Hypotonicity also activated Ca2+ entry, which was required for subsequent RVD.
      Ca2+ entry was associated with a distinct nonselective cation current that was
      activated by 4alphaPDD and inhibited by ruthenium red, suggesting involvement of
      TRPV4. Consistent with this, endogenous TRPV4 was detected in cells and in the
      apical region of acini along AQP5. Importantly, acinar cells from mice lacking
      either TRPV4 or AQP5 displayed greatly reduced Ca2+ entry and loss of RVD in
      response to hypotonicity, although the extent of cell swelling was similar.
      Expression of N terminus-deleted AQP5 suppressed TRPV4 activation and RVD but not
      cell swelling. Furthermore, hypotonicity increased the association and surface
      expression of AQP5 and TRPV4. Both these effects and RVD were reduced by actin
      depolymerization. These data demonstrate that (i) activation of TRPV4 by
      hypotonicity depends on AQP5, not on cell swelling per se, and (ii) TRPV4 and
      AQP5 concertedly control regulatory volume decrease. These data suggest a
      potentially important role for TRPV4 in salivary gland function.

PMID- 16571725
TI  - Role of STAT3 in type I interferon responses. Negative regulation of STAT1
      dependent inflammatory gene activation.
AB  - Type I interferons (IFNalpha/beta) induce antiviral responses and have
      immunomodulatory effects that can either promote or suppress immunity and
      inflammation. In myeloid cells IFNalpha/beta activates signal transducers and
      activators of transcription STAT1, STAT2, and STAT3. STAT1 and STAT2 mediate the
      antiviral and inflammatory effects of IFNalpha/beta, but the function of
      IFNalpha/beta-activated STAT3 is not known. We investigated the role of STAT3 in
      type I IFN signaling in myeloid cells by modulating STAT3 expression and the
      intensity of STAT3 activation using overexpression and RNA interference and
      determining the effects on downstream signaling and gene expression. IFNalpha
      activated STAT3 inhibited STAT1-dependent gene activation, thereby down
      regulating IFNalpha-mediated induction of inflammatory mediators such as the
      chemokines CXCL9 (Mig) and CXCL10 (IP-10). At the same time, IFNalpha-activated
      STAT3 supported ISGF-3-dependent induction of antiviral genes. STAT3 did not
      suppress STAT1 tyrosine phosphorylation or nuclear translocation but instead
      sequestered STAT1 and suppressed the formation of DNA-binding STAT1 homodimers.
      These results identify a regulatory function for STAT3 in attenuating the
      inflammatory properties of type I IFNs and provide a mechanism of suppression of
      STAT1 function that differs from previously described suppression of tyrosine
      phosphorylation. The results suggest that changes in the relative expression and
      activation of STAT1 and STAT3 that occur during immune responses determine the
      nature of cellular responses to type I IFNs.

PMID- 16571724
TI  - Up-regulation of the KLF2 transcription factor by fluid shear stress requires
      nucleolin.
AB  - We have previously characterized the regulation of the KLF2 transcription factor
      gene by describing an induction complex that binds to and regulates its promoter.
      In the present study, by using DNA affinity chromatography and mass spectrometry,
      we have identified nucleolin as an additional protein that binds to a palindromic
      response region in the KLF2 promoter. The presence of nucleolin on the KLF2
      promoter in macrophages was verified by electrophoretic mobility shift assays.
      Interestingly, in mouse and human endothelial cell lines, electrophoretic
      mobility shift assays and chromatin immunoprecipitation analyses indicated that
      nucleolin binds the KLF2 promoter only upon application of fluid shear stress.
      Pretreatment of the endothelial cells with LY294002, a specific inhibitor of
      phosphatidylinositol 3-kinase (PI3K), blocked the shear stress-induced binding of
      nucleolin to the promoter, demonstrating its PI3K-dependent regulation.
      Additionally, nucleolin exhibited dynamic flow-specific, PI3K-dependent
      alterations in size. Anti-nucleolin antibodies interacted with a 110-kDa form in
      static endothelial cells and with several catalytic forms that changed in
      abundance after the application of shear stress. Immunoprecipitation experiments
      demonstrated that fluid flow induced the interaction of nucleolin with the p85
      regulatory subunit of PI3K. Finally, introduction of small interfering RNAs
      targeting the nucleolin genetic sequence selectively reduced nucleolin expression
      and was sufficient to block the induction of KLF2 by shear stress. These data
      support a general role for nucleolin in gene regulation and identify it as a
      novel factor involved in regulation of KLF2 expression.

PMID- 16571726
TI  - The yeast prion Ure2p native-like assemblies are toxic to mammalian cells
      regardless of their aggregation state.
AB  - The yeast prion Ure2p assembles in vitro into oligomers and fibrils retaining the
      alpha-helix content and binding properties of the soluble protein. Here we show
      that the different forms of Ure2p native-like assemblies (dimers, oligomers, and
      fibrils) are similarly toxic to murine H-END cells when added to the culture
      medium. Interestingly, the amyloid fibrils obtained by heat treatment of the
      toxic native-like fibrils appear harmless. Moreover, the Ure2p C-terminal domain,
      lacking the N-terminal segment necessary for aggregation but containing the
      glutathione binding site, is not cytotoxic. This finding strongly supports the
      idea that Ure2p toxicity depends on the structural properties of the flexible N
      terminal prion domain and can therefore be considered as an inherent feature of
      the protein, unrelated to its aggregation state but rather associated with a
      basic toxic fold shared by all of the Ure2p native-like assemblies. Indeed, the
      latter are able to interact with the cell surface, leading to alteration of
      calcium homeostasis, membrane permeabilization, and oxidative stress, whereas the
      heat-treated amyloid fibrils do not. Our results support the idea of a general
      mechanism of toxicity of any protein/peptide aggregate endowed with structural
      features, making it able to interact with cell membranes and to destabilize them.
      This evidence extends the widely accepted view that the toxicity by protein
      aggregates is restricted to amyloid prefibrillar aggregates and provides new
      insights into the mechanism by which native-like oligomers compromise cell
      viability.

PMID- 16571727
TI  - REV3 and REV1 play major roles in recombination-independent repair of DNA
      interstrand cross-links mediated by monoubiquitinated proliferating cell nuclear
      antigen (PCNA).
AB  - DNA interstrand cross-links (ICLs) are the most cytotoxic lesions to eukaryotic
      genome and are repaired by both homologous recombination-dependent and 
      independent mechanisms. To better understand the role of lesion bypass
      polymerases in ICL repair, we investigated recombination-independent repair of
      ICLs in REV3 and REV1 deletion mutants constructed in avian DT40 cells and mouse
      embryonic fibroblast cells. Our results showed that Rev3 plays a major role in
      recombination-independent ICL repair, which may account for the extreme
      sensitivity of REV3 mutants to cross-linking agents. This result raised the
      possibility that the NER gap synthesis, when encountering an adducted base
      present in the ICL repair intermediate, can lead to recruitment of Rev3,
      analogous to the recruitment of polymerase eta during replicative synthesis.
      Indeed, the monoubiquitination-defective Proliferating Cell Nuclear Antigen
      (PCNA) mutant exhibits impaired recombination-independent ICL repair as well as
      drastically reduced mutation rate, indicating that the PCNA switch is utilized to
      enable lesion bypass during DNA repair synthesis. Analyses of a REV1 deletion
      mutant also revealed a significant reduction in recombination-independent ICL
      repair, suggesting that Rev1 cooperates with Rev3 in recombination-independent
      ICL repair. Moreover, deletion of REV3 or REV1 significantly altered the spectrum
      of mutations resulting from ICL repair, further confirming their involvement in
      mutagenic repair of ICLs.

PMID- 16571728
TI  - Cernunnos interacts with the XRCC4 x DNA-ligase IV complex and is homologous to
      the yeast nonhomologous end-joining factor Nej1.
AB  - DNA double strand breaks are considered as the most harmful DNA lesions and are
      repaired by either homologous recombination or nonhomologous end joining (NHEJ).
      A new NHEJ factor, Cernunnos, has been identified, the defect of which leads to a
      severe immunodeficiency condition associated with microcephaly and other
      developmental defects in humans. This presentation is reminiscent to that of DNA
      ligase IV deficiency and suggests a possible interplay between Cernunnos and the
      XRCC4 x DNA-ligase IV complex. We show here that Cernunnos physically interacts
      with the XRCC4 x DNA-ligase IV complex. Moreover, a combination of sensitive
      methods of sequence analysis revealed that Cernunnos can be associated with the
      XRCC4 family of proteins and that it corresponds to the genuine homolog of the
      yeast Nej1 protein. Altogether these results shed new lights on the last step,
      the DNA religation, of the NHEJ pathway.

PMID- 16571729
TI  - Survey of catalytic residues and essential roles of glutamate-alpha170 and
      aspartate-alpha335 in coenzyme B12-dependent diol dehydratase.
AB  - The importance of each active-site residue in adenosylcobalamin-dependent diol
      dehydratase of Klebsiella oxytoca was estimated using mutant enzymes in which one
      of the residues interacting with substrate and/or K(+) was mutated to Ala or
      another amino acid residue. The Ealpha170A and Dalpha335A mutants were totally
      inactive, and the Halpha143A mutant showed only a trace of activity, indicating
      that Glu-alpha170, Asp-alpha335, and His-alpha143 are catalytic residues. The
      Qalpha141A, Qalpha296A, and Salpha362A mutants showed partial activity. It was
      suggested from kinetic parameters that Gln-alpha296 is important for substrate
      binding and Gln-alpha296 and Gln-alpha141 for preventing the enzyme from
      mechanism-based inactivation. The Ealpha221A, Ealpha170H, and Dalpha335A did not
      form the (alphabetagamma)(2) complex, suggesting that these mutations indirectly
      disrupt subunit contacts. Among other Glu-alpha170 and Asp-alpha335 mutants,
      Ealpha170D and Ealpha170Q were 2.2 +/- 0.3% and 0.02% as active as the wild-type
      enzyme, respectively, whereas Dalpha335N was totally inactive. Kinetic analysis
      indicated that the presence and the position of a carboxyl group in the residue
      alpha170 are essential for catalysis as well as for the continuous progress of
      catalytic cycles. It was suggested that the roles of Glu-alpha170 and Asp
      alpha335 are to participate in the binding of substrate and intermediates and
      keep them appropriately oriented and to function as a base in the dehydration of
      the 1,1-diol intermediate. In addition, Glu-alpha170 seems to stabilize the
      transition state for the hydroxyl group migration from C2 to C1 by accepting the
      proton of the spectator hydroxyl group on C1.

PMID- 16571731
TI  - Behavioral reference frames for planning human reaching movements.
AB  - At some stage in the process of a sensorimotor transformation for a reaching
      movement, information about the current position of the hand and information
      about the location of the target must be encoded in the same frame of reference
      to compute the hand-to-target difference vector. Two main hypotheses have been
      proposed regarding this reference frame: an eye-centered and a body-centered
      frame. Here we evaluated these hypotheses using the pointing errors that subjects
      made when planning and executing arm movements to memorized targets starting from
      various initial hand positions while keeping gaze fixed in various directions.
      One group of subjects (n = 10) was tested without visual information about hand
      position during movement planning (unseen-hand condition); another group (n = 8)
      was tested with hand and target position simultaneously visible before movement
      onset (seen-hand condition). We found that both initial hand position and gaze
      fixation direction had a significant effect on the magnitude and direction of the
      pointing error. Errors were significantly smaller in the seen-hand condition. For
      both conditions, though, a reference frame analysis showed that the errors arose
      at an eye- or hand-centered stage or both, but not at a body-centered stage. As a
      common reference frame is required to specify a movement vector, these results
      suggest that an eye-centered mechanism is involved in integrating target and hand
      position in programming reaching movements. We discuss how simple gain elements
      modulating the eye-centered target and hand-position signals can account for
      these results.

PMID- 16571733
TI  - Binaural response properties of low-frequency neurons in the gerbil dorsal
      nucleus of the lateral lemniscus.
AB  - Differences in intensity and arrival time of sounds at the two ears, interaural
      intensity and time differences (IID, ITD), are the chief cues for sound
      localization. Both cues are initially processed in the superior olivary complex
      (SOC), which projects to the dorsal nucleus of the lateral lemniscus (DNLL) and
      the auditory midbrain. Here we present basic response properties of low-frequency
      (< 2 kHz) DNLL neurons and their binaural sensitivity to ITDs and IIDs in the
      anesthetized gerbil. We found many neurons showing binaural properties similar to
      those reported for SOC neurons. IID-properties were similar to that of the
      contralateral lateral superior olive (LSO). A majority of cells had an ITD
      sensitivity resembling that of either the ipsilateral medial superior olive (MSO)
      or the contralateral LSO. A smaller number of cells displayed intermediate types
      of ITD sensitivity. In neurons with MSO-like response ITDs that evoked maximal
      discharges were mostly outside of the range of ITDs the gerbil naturally
      experiences. The maxima of the first derivative of their ITD-functions (steepest
      slope), however, were well within the physiological range of ITDs. This finding
      is consistent with the concept of a population rather than a place code for ITDs.
      Moreover, we describe several other binaural properties as well as physiological
      and anatomical evidence for a small but significant input from the contralateral
      MSO. The large number of ITD-sensitive low-frequency neurons implicates a
      substantial role for the DNLL in ITD processing and promotes this nucleus as a
      suitable model for further studies on ITD-coding.

PMID- 16571730
TI  - Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent
      activation of caspase-8 and the mitochondrial death pathway.
AB  - In vitro studies of hepatocytes have implicated over-activation of c-Jun N
      terminal kinase (JNK) signaling as a mechanism of tumor necrosis factor-alpha
      (TNF)-induced apoptosis. However, the functional significance of JNK activation
      and the role of specific JNK isoforms in TNF-induced hepatic apoptosis in vivo
      remain unclear. JNK1 and JNK2 function was, therefore, investigated in the TNF
      dependent, galactosamine/lipopolysaccharide (GalN/LPS) model of liver injury. The
      toxin GalN converted LPS-induced JNK signaling from a transient to prolonged
      activation. Liver injury and mortality from GalN/LPS was equivalent in wild-type
      and jnk1-/- mice but markedly decreased in jnk2-/- mice. This effect was not
      secondary to down-regulation of TNF receptor 1 expression or TNF production. In
      the absence of jnk2, the caspase-dependent, TNF death pathway was blocked, as
      reflected by the failure of caspase-3 and -7 and poly(ADP-ribose) polymerase
      cleavage to occur. JNK2 was critical for activation of the mitochondrial death
      pathway, as in jnk2-/- mice Bid cleavage and mitochondrial translocation and
      cytochrome c release were markedly decreased. This effect was secondary to the
      failure of jnk2-/- mice to activate caspase-8. Liver injury and caspase
      activation were similarly decreased in jnk2 null mice after GalN/TNF treatment.
      Ablation of jnk2 did not inhibit GalN/LPS-induced c-Jun kinase activity, although
      activity was completely blocked in jnk1-/- mice. Toxic liver injury is,
      therefore, associated with JNK over-activation and mediated by JNK2 promotion of
      caspase-8 activation and the TNF mitochondrial death pathway through a mechanism
      independent of c-Jun kinase activity.

PMID- 16571732
TI  - Roll rotation cues influence roll tilt perception assayed using a somatosensory
      technique.
AB  - We investigated how the nervous system processes ambiguous cues from the otolith
      organs by measuring roll tilt perception elicited by two motion paradigms. In one
      paradigm (tilt), eight subjects were sinusoidally tilted in roll with the axis of
      rotation near ear level. Stimulus frequencies ranged from 0.005 to 0.7 Hz, and
      the peak amplitude of tilt was 20 degrees . During this paradigm, subjects
      experienced a sinusoidal variation of interaural gravitational force with a peak
      of 0.34 g. The second motion paradigm (translation) was designed to yield the
      same sinusoidal variation in interaural force but did not include a roll canal
      cue. This was achieved by sinusoidally translating the subjects along their
      interaural axis. For the 0.7-Hz translation trial, the subjects were simply
      translated from side to side. A centrifuge was used for the 0.005- to 0.5-Hz
      translation trials; the subjects were rotated in yaw at 250 degrees /s for 5 min
      before initiating sinusoidal translations yielding an interaural otolith stimulus
      composed of both centrifugal and radial acceleration. Using a somatosensory task
      to measure roll tilt perception, we found substantial differences in tilt
      perception during the two motion paradigms. Because the primary difference
      between the two motion paradigms was the presence of roll canal cues during roll
      tilt trials, these perceptual differences suggest that canal cues influence tilt
      perception. Specifically, rotational cues provided by the semicircular canals
      help the CNS resolve ambiguous otolith cues during head tilt, yielding more
      accurate tilt perception.

PMID- 16571734
TI  - Interhemispheric integration at different spatial scales: the evidence from EEG
      coherence and FMRI.
AB  - The early visual system processes different spatial frequencies (SFs) separately.
      To examine where in the brain the scale-specific information is integrated, we
      mapped the neural assemblies engaged in interhemispheric coupling with
      electroencephalographic (EEG) coherence and blood-oxygen-level dependent (BOLD)
      signal. During similar EEG and functional magnetic resonance imaging (fMRI)
      experiments, our subjects viewed centrally presented bilateral gratings of
      different SF (0.25-8.0 cpd), which either obeyed Gestalt grouping rules (iso
      oriented, IG) or violated them (orthogonally oriented, OG). The IG stimuli (0.5
      4.0 cpd) synchronized EEG at discrete beta frequencies (beta1, beta2) and
      increased BOLD (0.5 and 2.0 cpd tested) in ventral (around collateral sulcus) and
      dorsal (parieto-occipital fissure) regions compared with OG. At both SF, the
      beta1 coherence correlated with the ventral activations, whereas the beta2
      coherence correlated with the dorsal ones. Thus distributed neural substrates
      mediated interhemispheric integration at single SF. The relative impact of the
      ventral versus dorsal networks was modulated by the SF of the stimulus.

PMID- 16571736
TI  - Integration of evoked responses in supragranular cortex studied with optical
      recordings in vivo.
AB  - Complex representations in sensory cortices rely on the integration of inputs
      that overlap temporally and spatially, particularly in supragranular layers, yet
      the spatiotemporal dynamics of this synaptic integration are largely unknown. The
      rodent somatosensory system offers an excellent opportunity to study these
      dynamics because of the overlapping functional representations of single-whisker
      inputs. We recorded responses in mouse primary somatosensory (barrel) cortex to
      single and paired whisker deflections using high-speed voltage-sensitive dye
      imaging. Responses to paired deflections at intervals of 0 and 10 ms summed
      sublinearly, producing a single transient smaller in amplitude than the sum of
      the component responses. At longer intervals of 50 and 100 ms, the response to
      the second deflection was reduced in amplitude and limited spatially relative to
      control. Between 100 and 200 ms, the response to the second deflection recovered
      and often showed areas of facilitation. With increasing interstimulus interval
      from 50 to 200 ms, recovery of the second response occurred from the second
      stimulated whisker's barrel column outward. In contrast to results with paired
      whisker stimulation, when a whisker deflection was preceded by a weak electrical
      stimulus applied to the neighboring cortex, the summation of evoked responses was
      predominantly linear at all intervals tested. Thus under our conditions, the
      linearity of response summation in cortex was not predicted by the amplitudes of
      the component responses on a column-by-column basis, but rather by the timing and
      nature of the inputs.

PMID- 16571735
TI  - Somatostatin presynaptically inhibits both GABA and glutamate release onto rat
      basal forebrain cholinergic neurons.
AB  - A whole cell patch-clamp study was carried out in slices obtained from young rat
      brain to elucidate the roles of somatostatin in the modulation of synaptic
      transmission onto cholinergic neurons in the basal forebrain (BF), a region that
      contains cholinergic and GABAergic corticopetal neurons and somatostatin (SS)
      containing local circuit neurons. Cholinergic neurons within the BF were
      identified by in vivo prelabeling with Cy3 IgG. Because in many cases SS is
      contained in GABAergic neurons in the CNS, we investigated whether exogenously
      applied SS can influence GABAergic transmission onto cholinergic neurons. Bath
      application of somatostatin (1 muM) reduced the amplitude of the evoked GABAergic
      inhibitory presynaptic currents (IPSCs) in cholinergic neurons. SS also reduced
      the frequency of miniature IPSCs (mIPSCs) without affecting their amplitude
      distribution. SS-induced effect on the mIPSC frequency was significantly larger
      in the solution containing 7.2 mM Ca(2+) than in the standard (2.4 mM Ca(2+))
      external solution. Similar effects were observed in the case of non-NMDA
      glutamatergic excitatory postsynaptic currents (EPSCs). SS inhibited the
      amplitude of evoked EPSCs and reduced the frequency of miniature EPSCs dependent
      on the external Ca(2+) concentration with no effect on their amplitude
      distribution. Pharmacological analyses using SS-receptor subtype-specific drugs
      suggest that SS-induced action of the IPSCs is mediated mostly by the sst(2)
      subtype, whereas sst subtypes mediating SS-induced inhibition of EPSCs are mainly
      sst(1) or sst(4). These findings suggest that SS presynaptically inhibits both
      GABA and glutamate release onto BF cholinergic neurons in a Ca(2+)-dependent way,
      and that SS-induced effect on IPSCs and EPSCs are mediated by different sst
      subtypes.

PMID- 16571738
TI  - Distinct time scales in cortical discrimination of natural sounds in songbirds.
AB  - Understanding how single cortical neurons discriminate between sensory stimuli is
      fundamental to providing a link between cortical neural responses and perception.
      The discrimination of sensory stimuli by cortical neurons has been intensively
      investigated in the visual and somatosensory systems. However, relatively little
      is known about discrimination of sounds by auditory cortical neurons. Auditory
      cortex plays a particularly important role in the discrimination of complex
      sounds, e.g., vocal communication sounds. The rich dynamic structure of such
      complex sounds on multiple time scales motivates two questions regarding cortical
      discrimination. How does discrimination depend on the temporal resolution of the
      cortical response? How does discrimination accuracy evolve over time? Here we
      investigate these questions in field L, the analogue of primary auditory cortex
      in zebra finches, analyzing temporal resolution and temporal integration in the
      discrimination of conspecific songs (songs of the bird's own species) for both
      anesthetized and awake subjects. We demonstrate the existence of distinct time
      scales for temporal resolution and temporal integration and explain how they
      arise from cortical neural responses to complex dynamic sounds.

PMID- 16571737
TI  - Spike-frequency adaptation and intrinsic properties of an identified, looming
      sensitive neuron.
AB  - We investigated in vivo the characteristics of spike-frequency adaptation and the
      intrinsic membrane properties of an identified, looming-sensitive interneuron of
      the locust optic lobe, the lobula giant movement detector (LGMD). The LGMD had an
      input resistance of 4-5 MOmega, a membrane time constant of about 8 ms, and
      exhibited inward rectification and rebound spiking after hyperpolarizing current
      pulses. Responses to depolarizing current pulses revealed the neuron's intrinsic
      bursting properties and pronounced spike-frequency adaptation. The
      characteristics of adaptation, including its time course, the attenuation of the
      firing rate, the mutual dependency of these two variables, and their dependency
      on injected current, closely followed the predictions of a model first proposed
      to describe the adaptation of cat visual cortex pyramidal neurons in vivo. Our
      results thus validate the model in an entirely different context and suggest that
      it might be applicable to a wide variety of neurons across species. Spike
      frequency adaptation is likely to play an important role in tuning the LGMD and
      in shaping the variability of its responses to visual looming stimuli.

PMID- 16571739
TI  - Increases in alpha oscillatory power reflect an active retinotopic mechanism for
      distracter suppression during sustained visuospatial attention.
AB  - Human electrophysiological (EEG) studies have demonstrated the involvement of
      alpha band (8- to 14-Hz) oscillations in the anticipatory biasing of attention.
      In the context of visual spatial attention within bilateral stimulus arrays,
      alpha has exhibited greater amplitude over parietooccipital cortex contralateral
      to the hemifield required to be ignored, relative to that measured when the same
      hemifield is to be attended. Whether this differential effect arises solely from
      alpha desynchronization (decreases) over the "attending" hemisphere, from
      synchronization (increases) over the "ignoring" hemisphere, or both, has not been
      fully resolved. This is because of the confounding effect of externally evoked
      desynchronization that occurs involuntarily in response to visual cues. Here,
      bilateral flickering stimuli were presented simultaneously and continuously over
      entire trial blocks, such that externally evoked alpha desynchronization is
      equated in precue baseline and postcue intervals. Equivalent random letter
      sequences were superimposed on the left and right flicker stimuli. Subjects were
      required to count the presentations of the target letter "X" at the cued
      hemifield over an 8-s period and ignore the sequence in the opposite hemifield.
      The data showed significant increases in alpha power over the ignoring hemisphere
      relative to the precue baseline, observable for both cue directions. A strong
      attentional bias necessitated by the subjective difficulty in gating the
      distracting letter sequence is reflected in a large effect size of 2.1 (eta2 =
      0.82), measured from the attention x hemisphere interaction. This strongly
      suggests that alpha synchronization reflects an active attentional suppression
      mechanism, rather than a passive one reflecting "idling" circuits.

PMID- 16571741
TI  - Psychosocial work environment and incidence of severe depressive symptoms:
      prospective findings from a 5-year follow-up of the Danish work environment
      cohort study.
AB  - The authors analyzed the impact of psychosocial work characteristics on the
      incidence of severe depressive symptoms among 4,133 (49% women) employees from a
      representative sample of the Danish workforce between 1995 and 2000. Psychosocial
      work characteristics at baseline included quantitative demands, influence at
      work, possibilities for development, social support from supervisors and
      coworkers, and job insecurity. Severe depressive symptoms were measured with the
      five-item Mental Health Inventory of the 36-item Short-Form Health Survey, with a
      cutoff point of 52. Women with low influence at work (relative risk (RR) = 2.17,
      95% confidence interval (CI): 1.23, 3.82) and low supervisor support (RR = 2.03,
      95% CI: 1.20, 3.43) were at increased risk for severe depressive symptoms after
      exclusion of cases at baseline and adjustment for sociodemographic factors,
      baseline depression score, and health behaviors. Further adjustments for
      socioeconomic position did not change the result substantially. Additional
      analyses showed that a one-standard deviation increase on the influence scale
      resulted in a 27% decreased risk of severe depressive symptoms. Among men, job
      insecurity predicted severe depressive symptoms (RR = 2.04, 95% CI: 1.02, 4.07).
      The findings indicate that the work environment influences the risk of developing
      severe depressive symptoms and that different factors play a role for men and
      women.

PMID- 16571740
TI  - An optimization principle for determining movement duration.
AB  - Movement duration is an integral component of motor control, but nearly all
      extant optimization models of motor planning prefix duration instead of
      explaining it. Here we propose a new optimization principle that predicts
      movement duration. The model assumes that the brain attempts to minimize movement
      duration under the constraint of meeting an accuracy criterion. The criterion is
      task and context dependent but is fixed for a given task and context. The model
      determines a unique duration as a trade-off between speed (time optimality) and
      accuracy (acceptable endpoint scatter). We analyzed the model for a linear motor
      plant, and obtained a closed-form equation for determining movement duration. By
      solving the equation numerically with specific plant parameters for the eye and
      arm, we found that the model can reproduce saccade duration as a function of
      amplitude (the main sequence), and arm-movement duration as a function of the
      ratio of target distance to size (Fitts's law). In addition, it explains the
      dependency of peak saccadic speed on amplitude and the dependency of saccadic
      duration on initial eye position. Furthermore, for arm movements, the model
      predicts a scaling relationship between peak velocity and distance and a
      reduction in movement duration with a moderate increase in viscosity. Finally,
      for a linear plant, our model predicts a neural control signal identical to that
      of the minimum-variance model set to the same movement duration. This control
      signal is a smooth function of time (except at the endpoint), in contrast to the
      discontinuous bang-bang control found in the time-optimal control literature. We
      suggest that one aspect of movement planning, as revealed by movement duration,
      may be to assign an endpoint accuracy criterion for a given task and context.

PMID- 16571742
TI  - Perceived safety of area of residence and exercise: a pan-European study.
AB  - The authors examined the association between perceived safety of neighborhood and
      likelihood of exercise among adult residents of eight European cities. Data were
      collected by a survey of neighborhood, housing, and health conducted by the World
      Health Organization in 2002 and 2003. Baseline category logistic regression
      models were fit to estimate the association between perceived safety and
      exercise, accounting for demographic and place-of-residence characteristics.
      Among women, perception of safety was associated with a 22% (95% confidence
      interval: 1.00, 1.54) and a 40% (95% confidence interval: 1.03, 1.91) elevation
      in the odds of occasional and frequent exercise, respectively. Among men,
      perception of safety was associated with a 39% elevation in the odds of
      occasional exercise, but there was no association with frequent exercise. If
      these findings were replicated, they would suggest that health promotion efforts
      could target residential areas without the need to identify specific persons.

PMID- 16571743
TI  - Wiring stability of the adult Drosophila olfactory circuit after lesion.
AB  - Neuronal wiring plasticity in response to experience or injury has been reported
      in many parts of the adult nervous system. For instance, visual or somatosensory
      cortical maps can reorganize significantly in response to peripheral lesions, yet
      a certain degree of stability is essential for neuronal circuits to perform their
      dedicated functions. Previous studies on lesion-induced neuronal reorganization
      have primarily focused on systems that use continuous neural maps. Here, we
      assess wiring plasticity in a discrete neural map represented by the adult
      Drosophila olfactory circuit. Using conditional expression of toxins, we
      genetically ablated specific classes of neurons and examined the consequences on
      their synaptic partners or neighboring classes in the adult antennal lobe. We
      find no alteration of connection specificity between olfactory receptor neurons
      (ORNs) and their postsynaptic targets, the projection neurons (PNs). Ablating an
      ORN class maintains PN dendrites within their glomerular borders, and ORN axons
      normally innervating an adjacent target do not expand. Likewise, ablating PN
      classes does not alter their partner ORN axon connectivity. Interestingly, an
      increase in the contralateral ORN axon terminal density occurs in response to the
      removal of competing ipsilateral ORNs. Therefore, plasticity in this circuit can
      occur but is confined within a glomerulus, thereby retaining the wiring
      specificity of ORNs and PNs. We conclude that, although adult olfactory neurons
      can undergo plastic changes in response to the loss of competition, the olfactory
      circuit overall is extremely stable in preserving segregated information channels
      in this discrete map.

PMID- 16571744
TI  - Delayed transplantation of adult neural precursor cells promotes remyelination
      and functional neurological recovery after spinal cord injury.
AB  - Spinal cord injury (SCI) results in loss of oligodendrocytes demyelination of
      surviving axons and severe functional impairment. Spontaneous remyelination is
      limited. Thus, cell replacement therapy is an attractive approach for myelin
      repair. In this study, we transplanted adult brain-derived neural precursor cells
      (NPCs) isolated from yellow fluorescent protein-expressing transgenic mice into
      the injured spinal cord of adult rats at 2 and 8 weeks after injury, which
      represents the subacute and chronic phases of SCI. A combination of growth
      factors, the anti-inflammatory drug minocycline, and cyclosporine A
      immunosuppression was used to enhance the survival of transplanted adult NPCs.
      Our results show the presence of a substantial number of surviving NPCs in the
      injured spinal cord up to 10 weeks after transplantation at the subacute stage of
      SCI. In contrast, cell survival was poor after transplantation into chronic
      lesions. After subacute transplantation, grafted cells migrated >5 mm rostrally
      and caudally. The surviving NPCs integrated principally along white-matter tracts
      and displayed close contact with the host axons and glial cells. Approximately
      50% of grafted cells formed either oligodendroglial precursor cells or mature
      oligodendrocytes. NPC-derived oligodendrocytes expressed myelin basic protein and
      ensheathed the axons. We also observed that injured rats receiving NPC
      transplants had improved functional recovery as assessed by the Basso, Beattie,
      and Bresnahan Locomotor Rating Scale and grid-walk and footprint analyses. Our
      data provide strong evidence in support of the feasibility of adult NPCs for cell
      based remyelination after SCI.

PMID- 16571745
TI  - Temporal control of Rac in Schwann cell-axon interaction is disrupted in NF2
      mutant schwannoma cells.
AB  - Schwann cell-axon interaction is the hallmark feature of peripheral nerves, yet
      the intracellular signals underlying this interaction are unknown. Schwann cells
      extend processes and migrate on developing axons before differentiation,
      requiring coordinated regulation of the Schwann cell cytoskeleton. Small GTPases
      of the Rho family, including Rho, Rac, and cell division cycle 42, regulate the
      actin cytoskeleton. The neurofibromatosis type 2 (NF2) gene is commonly mutated
      in schwannomas, Schwann cell tumors that contain cells lacking axon interaction.
      NF2 is involved in suppression of Rac signaling, and cultured schwannoma cells
      contain elevated, GTP-bound, active Rac. Despite these previous studies, a causal
      relationship between Rac activation and the abnormal cellular morphology of
      schwannoma is unknown. We used fluorescence resonance energy transfer to follow
      Rac activity in normal human Schwann cells and schwannoma cells during
      interaction with neurons. Normal Schwann cells elongated processes along neurites
      under low Rac activity. Schwannoma cells showed high Rac activity at distal
      regions of the cells and failed to align processes with neurites. Application of
      a Rac-specific inhibitor, the chemical compound NSC23766, to schwannoma cells
      restored neuronal interaction. The data support the significance of regulated Rac
      signaling in mediating Schwann cell-axon interaction and suggest that controlling
      Rac activity as a possible therapy for schwannomas.

PMID- 16571746
TI  - CD8+ lymphocyte-mediated injury of dorsal root ganglion neurons during lentivirus
      infection: CD154-dependent cell contact neurotoxicity.
AB  - Neuronal damage in dorsal root ganglia (DRGs) with accompanying axonal injury is
      a key feature of human immunodeficiency virus (HIV)-related distal sensory
      polyneuropathy (DSP). In a model of HIV-related DSP, we observed numerous CD3+ T
      lymphocytes (p < 0.05) in DRGs from feline immunodeficiency virus (FIV)-infected
      animals, which also exhibited low CD4+ and high CD8+ lymphocyte levels in blood
      accompanied by a selective loss of small-diameter sural nerve axons (p < 0.05).
      FIV-infected lymphocytes cocultured with syngeneic DRGs caused neuronal damage,
      indicated by neurite retraction, neuronal soma atrophy, and loss (p < 0.05). In
      contrast, supernatants from FIV-infected or uninfected lymphocytes were minimally
      neurotoxic, despite high FIV virion levels. Among lymphocyte subsets cocultured
      with DRG cultures, CD8+ T cells from both FIV-infected and uninfected lymphocytes
      selectively caused DRG neuronal injury (p < 0.05). FIV-infected CD8+ T cells
      showed markedly increased CD154 expression (p < 0.05), whereas neurons were the
      predominant cells expressing CD40 in DRGs. Blocking CD154 on activated CD8+ T
      cells protected DRG neurons (p < 0.05). These findings indicated that CD8+ T
      cells were principal effectors of DRG neuronal injury after FIV infection through
      a CD40-CD154 interaction in a cell contact-dependent manner.

PMID- 16571747
TI  - Synergistic control of protein kinase Cgamma activity by ionotropic and
      metabotropic glutamate receptor inputs in hippocampal neurons.
AB  - Conventional protein kinase C (PKC) isoforms are abundant neuronal signaling
      proteins with important roles in regulating synaptic plasticity and other
      neuronal processes. Here, we investigate the role of ionotropic and metabotropic
      glutamate receptor (iGluR and mGluR, respectively) activation on the generation
      of Ca2+ and diacylglycerol (DAG) signals and the subsequent activation of the
      neuron-specific PKCgamma isoform in hippocampal neurons. By combining Ca2+
      imaging with total internal reflection microscopy analysis of specific
      biosensors, we show that elevation of both Ca2+ and DAG is necessary for
      sustained translocation and activation of EGFP (enhanced green fluorescent
      protein)-PKCgamma. Both DAG production and PKCgamma translocation were localized
      processes, typically observed within discrete microdomains along the dendritic
      branches. Markedly, intermediate-strength NMDA receptor (NMDAR) activation or
      moderate electrical stimulation generated Ca2+ but no DAG signals, whereas mGluR
      activation generated DAG but no Ca2+ signals. Both receptors were needed for
      PKCgamma activation. This suggests that a coincidence detection process exists
      between iGluRs and mGluRs that relies on a molecular coincidence detection
      process based on the corequirement of Ca2+ and DAG for PKCgamma activation.
      Nevertheless, the requirement for costimulation with mGluRs could be overcome for
      maximal NMDAR stimulation through a direct production of DAG via activation of
      the Ca2+-sensitive PLCdelta (phospholipase Cdelta) isoform. In a second important
      exception, mGluRs were sufficient for PKCgamma activation in neurons in which
      Ca2+ stores were loaded by previous electrical activity. Together, the dual
      activation requirement for PKCgamma provides a plausible molecular interpretation
      for different synergistic contributions of mGluRs to long-term potentiation and
      other synaptic plasticity processes.

PMID- 16571748
TI  - Participation of sodium currents in burst generation and control of membrane
      excitability in mesencephalic trigeminal neurons.
AB  - Subthreshold sodium currents are important in sculpting neuronal discharge and
      have been implicated in production and/or maintenance of subthreshold membrane
      oscillations and burst generation in mesencephalic trigeminal neurons (Mes V).
      Moreover, recent data suggest that, in some CNS neurons, resurgent sodium
      currents contribute to production of high-frequency burst discharge. In the
      present study, we sought to determine more directly the participation of these
      currents during Mes V electrogenesis using the action potential-clamp method. In
      postnatal day 8-14 rats, the whole-cell patch-clamp method was used to record
      sodium currents by subtraction in response to application of TTX in voltage-clamp
      mode using the action potential waveform as the command protocol. We found that
      TTX-sensitive sodium current is the main inward current flowing during the
      interspike interval, compared with the h-current (Ih) and calcium currents.
      Furthermore, in addition to the transient sodium current that flows during the
      upstroke of action potential, we show that resurgent sodium current flows at the
      peak of afterhyperpolarization and persistent sodium current flows in the middle
      of the interspike interval to drive high-frequency firing. Additionally,
      transient, resurgent, and persistent sodium current components showed voltage-
      and time-dependent slow inactivation, suggesting that slow inactivation of these
      currents can contribute to burst termination. The data suggest an important role
      for these components of the sodium current in Mes V neuron electrogenesis.

PMID- 16571749
TI  - Rostral elements of sympatho-motor circuitry: a virally mediated transsynaptic
      tracing study.
AB  - Numerous physiological and emotionally motivated behaviors, including locomotion,
      exercise, escape, and attack behaviors as well as passive coping responses,
      require concomitant activation of motor and sympathetic efferents. Such
      functional heterogeneity suggests the existence of dual function neurons that can
      simultaneously coordinate motor and sympathetic output. Because previous
      physiological investigations have implicated a number of mesencephalic and
      telencephalic regions in mediating these behaviors, we hypothesized the presence
      of dual function sympatho-motor neurons in these neural structures. To test this
      hypothesis, we used recombinant strains of the pseudorabies virus (PRV) for
      transsynaptic tract-tracing. PRV-152, a strain that expresses enhanced green
      fluorescent protein, was injected into sympathectomized gastrocnemius muscle,
      whereas PRV-BaBlu, which expresses beta-galactosidase, was injected into the
      adrenal gland in the same animals. Although coinfected neurons were detected in a
      number of mesencephalic and telencephalic regions, >50% of such neurons were
      located within specific subdivisions of two general areas: the hypothalamus and
      periaqueductal gray. These subdivisions included the ventrolateral periaqueductal
      gray, dorsomedial hypothalamus, dorsolateral lateral hypothalamus, and ventral
      portion of the medial parvocellular subdivision of the paraventricular nucleus of
      the hypothalamus (PVN). A subset of the sympatho-motor neurons within the PVN
      also contained either arginine vasopressin or oxytocin. This sympatho-motor
      circuitry likely plays an important role in mediating different aspects of stress
      responses and emotionally motivated behaviors.

PMID- 16571750
TI  - Gap junctions among dendrites of cortical GABAergic neurons establish a dense and
      widespread intercolumnar network.
AB  - Gap junctions are common between cortical GABAergic interneurons but little is
      known about their quantitative distribution along dendritic profiles. Here, we
      provide direct morphological evidence that parvalbumin-containing GABAergic
      neurons in layer 2/3 of the cat visual cortex form dense and far-ranging networks
      through dendritic gap junctions. Gap junction-coupled networks of parvalbumin
      neurons were visualized using connexin36 immunohistochemistry and confocal laser
      scanning microscopy (CLSM). The direct correspondence of connexin36-immunopositve
      puncta and gap junctions was confirmed by examining the same structures in both
      CLSM and electron microscopy. Single parvalbumin neurons with large somata (> or
      =200 microm2) formed 60.3 +/- 12.2 (mean +/- SD) gap junctions with other cells
      whereby these contacts were not restricted to proximal dendrites but occurred at
      distances of up to 380 microm from the soma. In a Sholl analysis of large-type
      parvalbumin neurons, 21.9 +/- 7.9 gap junctions were within 50 microm of the
      soma, 21.7 +/- 7.6 gap junctions in a segment between 50 and 100 microm, 11.2 +/-
      4.7 junctions between 100 and 150 microm, and 5.6 +/- 3.6 junctions were in more
      distal segments. Serially interconnected neurons could be traced laterally in a
      boundless manner through multiple gap junctions. Comparison to the orientation
      preference columns revealed that parvalbumin-immunoreactive cells distribute
      randomly whereby their large dendritic fields overlap considerably and cover
      different orientation columns. It is proposed that this dense and homogeneous
      electrical coupling of interneurons supports the precise synchronization of
      neuronal populations with differing feature preferences thereby providing a
      temporal frame for the generation of distributed representations.

PMID- 16571751
TI  - Intracerebral peripheral blood stem cell (CD34+) implantation induces
      neuroplasticity by enhancing beta1 integrin-mediated angiogenesis in chronic
      stroke rats.
AB  - Although stem cell-based treatments for stroke and other neurodegenerative
      diseases have advanced rapidly, there are still few clinical treatments
      available. In this study, rats receiving intracerebral peripheral blood
      hematopoietic stem cell (CD34+) (PBSC) transplantation showed much more
      improvement in neurological function after chronic cerebral ischemia in
      comparison with vehicle-treated control rats. Using laser-scanning confocal
      microscopy, implanted PBSCs were seen to differentiate into glial cells [GFAP+
      (glial fibrillary acidic protein-positive)], neurons [Nestin+, MAP-2+
      (microtubule-associated protein 2-positive), Neu-N+ (neuronal nuclear antigen
      positive)], and vascular endothelial cells [vWF+ (von Willebrand factor
      positive)], thereby enhancing neuroplastic effects in the ischemic brain.
      Cortical neuronal activity, as evaluated by 1H-MRS (proton magnetic resonance
      spectroscopy), also increased considerably in PBSC-treated rats compared with a
      vehicle-treated control group. In addition, PBSC implantation promoted the
      formation of new vessels, thereby increasing the local cortical blood flow in the
      ischemic hemisphere. These observations may be explained by the involvement of
      stem cell-derived macrophage/microglial cells, and beta1 integrin expression,
      which might enhance this angiogenic architecture over the ischemic brain.
      Furthermore, quantitative reverse transcription-PCR analysis showed significantly
      increased modulation of neurotrophic factor expression in the ischemic hemisphere
      of the PBSC-transplanted rats compared with vehicle-treated control rats. Thus,
      intracerebral PBSC transplantation might have potential as a therapeutic strategy
      for treating cerebrovascular diseases.

PMID- 16571752
TI  - Neural representation of object approach in a decision-making motor circuit.
AB  - Although behavior is ultimately guided by decision-making neurons and their
      associated networks, the mechanisms underlying neural decision-making in a
      behaviorally relevant context remain mostly elusive. To address this question, we
      analyzed goldfish escapes in response to distinct visual looming stimuli with
      high-speed video and compared them with electrophysiological responses of the
      Mauthner cell (M-cell), the threshold detector that initiates such behaviors.
      These looming stimuli evoke powerful and fast body-bend (C-start) escapes with
      response probabilities between 0.7 and 0.91 and mean latencies ranging from 142
      to 716 ms. Chronic recordings showed that these C-starts are correlated with M
      cell activity. Analysis of response latency as a function of the different
      optical parameters characterizing the stimuli suggests response threshold is
      closely correlated to a dynamically scaled function of angular retinal image
      size, (t), specifically kappa(t) = (t-delta x e(-beta(t-delta)), where the
      exponential term progressively reduces the weight of (t). Intracellular
      recordings show that looming stimuli typically evoked bursts of graded EPSPs with
      peak amplitudes up to 9 mV in the M-cell. The proposed scaling function kappa(t)
      predicts the slope of the depolarizing envelope of these EPSPs and the timing of
      the largest peak. An analysis of the firing rate of presynaptic inhibitory
      interneurons suggests the timing of the EPSP peak is shaped by an interaction of
      excitatory and inhibitory inputs to the M-cell and corresponds to the temporal
      window in which the probabilistic decision of whether or not to escape is
      reached.

PMID- 16571753
TI  - Persistent sodium current in layer 5 neocortical neurons is primarily generated
      in the proximal axon.
AB  - In addition to the well described fast-inactivating component of the Na+ current
      [transient Na+ current (INaT)], neocortical neurons also exhibit a low-voltage
      activated, slowly inactivating "persistent" Na+ current (INaP), which plays a
      role in determining neuronal excitability and synaptic integration. We
      investigated the Na+ channels responsible for INaP in layer 5 pyramidal cells
      using cell-attached and whole-cell recordings in neocortical slices. In
      simultaneous cell-attached and whole-cell somatic recordings, no persistent Na+
      channel activity was detected at potentials at which whole-cell INaP operates.
      Detailed kinetic analysis of late Na+ channel activity in cell-attached patches
      at 36 degrees C revealed that somatic Na+ channels do not demonstrate "modal
      gating" behavior and that the probability of single late openings is extremely
      low (<1.4 x 10(-4) or <0.02% of maximal open probability of INaT). Ensemble
      averages of these currents did not reveal a sustained component whose amplitude
      and voltage dependence could account for INaP as seen in whole-cell recordings.
      Local application of TTX to the axon blocked somatically recorded INaP, whereas
      somatic and dendritic application had little or no effect. Finally, simultaneous
      current-clamp recordings from soma and apical dendrite revealed that Na+ plateau
      potentials originate closer to the axon. Our data indicate that the primary
      source of INaP is in the spike initiation zone in the proximal axon. The focal
      axonal presence of regenerative subthreshold conductance with voltage and time
      dependence optimal to manipulate integration of synaptic input, spike threshold,
      and the pattern of repetitive firing provides the layer 5 pyramidal neuron with a
      mechanism for dynamic control of its gain.

PMID- 16571754
TI  - B-ephrin reverse signaling is required for NMDA-independent long-term
      potentiation of mossy fibers in the hippocampus.
AB  - The mossy fiber to CA3 pyramidal neuron synapse in the hippocampus displays an
      atypical form of NMDA receptor-independent long-term potentiation (LTP).
      Plasticity at this synapse is expressed in the presynaptic terminal as an
      elevated probability of neurotransmitter release. However, evidence indicates
      that postsynaptic mechanisms and trans-synaptic signaling through an association
      between postsynaptic EphB receptors and presynaptic B-ephrins are necessary for
      the induction of LTP. Here we show that ephrin-B3 protein is highly expressed in
      mossy fiber axons and terminals. There are specific deficits in mossy fiber LTP
      in mice in which the cytoplasmic C-terminal signaling domain of the ephrin-B3
      protein is replaced with beta-galactosidase. These deficits are not observed in
      ephrin-B3 null mutant mice because of functional redundancy by virtue of other B
      ephrins. These results indicate that B-ephrin reverse signaling into the
      presynaptic mossy fiber bouton is required for the induction of NMDA receptor
      independent LTP at this synapse.

PMID- 16571755
TI  - Early and simultaneous emergence of multiple hippocampal biomarkers of aging is
      mediated by Ca2+-induced Ca2+ release.
AB  - Age-dependent changes in multiple Ca2+-related electrophysiological processes in
      the hippocampus appear to be consistent biomarkers of aging, and several also
      correlate with cognitive decline. These findings have led to the hypothesis that
      a common mechanism of Ca2+ dyshomeostasis underlies aspects of aging-dependent
      brain impairment. However, some key predictions of this view remain untested,
      including that multiple Ca2+-related biomarkers should emerge concurrently during
      aging and their onset should also precede/coincide with initial signs of
      cognitive decline. Moreover, blocking a putative common source of dysregulated
      Ca2+ should eliminate aging differences. Here, we tested these predictions using
      combined electrophysiological, imaging, and pharmacological approaches in CA1
      neurons to determine the ages of onset (across 4-, 10-, 12-, 14-, and 23-month
      old F344 rats) of several established biomarkers, including the increases in the
      slow afterhyperpolarization, spike accommodation, and [Ca2+]i rise during
      repetitive synaptic stimulation. In addition, we tested the hypothesis that
      altered Ca2+-induced Ca2+ release (CICR) from ryanodine receptors, which can be
      triggered by L-type Ca2+ channels, provides a common source of dysregulated Ca2+
      in aging. Results showed that multiple aging biomarkers were first detectable at
      about the same age (12 months of age; approximately midlife), sufficiently early
      to influence initial cognitive decline. Furthermore, selectively blocking CICR
      with ryanodine slowed the Ca2+ rise during synaptic stimulation more in aged rat
      neurons and, notably, reduced or eliminated aging differences in the biomarkers.
      Thus, this study provides the first evidence that altered CICR plays a role in
      driving the early and simultaneous emergence in hippocampus of multiple Ca2+
      related biomarkers of aging.

PMID- 16571756
TI  - Involvement of matrix metalloproteinase in neuroblast cell migration from the
      subventricular zone after stroke.
AB  - After brain injury, neuroblast cells from the subventricular zone (SVZ) expand
      and migrate toward damaged tissue. The mechanisms that mediate these neurogenic
      and migratory responses remain to be fully dissected. Here, we show that
      bromodeoxyuridine-labeled and doublecortin-positive cells from the SVZ colocalize
      with the extracellular protease matrix metalloproteinase-9 (MMP-9) during the 2
      week recovery period after transient focal cerebral ischemia in mice. Treatment
      with the broad spectrum MMP inhibitor GM6001 significantly decreases the
      migration of doublecortin-positive cells that extend from the SVZ into the
      striatum. These data suggest that MMPs are involved in endogenous mechanisms of
      neurogenic migration as the brain seeks to heal itself after injury.

PMID- 16571757
TI  - Hippocampal long-term potentiation is supported by presynaptic and postsynaptic
      tyrosine receptor kinase B-mediated phospholipase Cgamma signaling.
AB  - Neurotrophins have been shown to play a critical role in activity-dependent
      synaptic plasticity such as long-term potentiation (LTP) in the hippocampus.
      Although the role of brain-derived neurotrophic factor (BDNF) and its tyrosine
      kinase receptor [tyrosine receptor kinase B (TrkB)] is well documented, it still
      remains unresolved whether presynaptic or postsynaptic activation of TrkB is
      involved in the induction of LTP. To address this question, we locally and
      specifically interfered with a downstream target of the TrkB receptor,
      phospholipase Cgamma (PLCgamma). We prevented PLCgamma signaling by
      overexpression of the PLCgamma pleckstrin homology (PH) domain with a Sindbis
      virus vector. The isolated PH domain has an inhibitory effect and thereby blocks
      endogenous PLCgamma signaling and consequently also IP3 production. Surprisingly,
      concurrent presynaptic and postsynaptic blockade of PLCgamma signaling was
      required to reduce LTP to levels comparable with those in TrkB and BDNF knock-out
      mice. Blockade of presynaptic or postsynaptic signaling alone did not result in a
      significant reduction of LTP.

PMID- 16571758
TI  - Kinematic and electromyographic study of the nociceptive withdrawal reflex in the
      upper limbs during rest and movement.
AB  - This study set out to evaluate nociceptive withdrawal reflex (NWR) excitability
      and the corresponding mechanical response in the upper limbs during rest and
      movement. We used a three-dimensional motion analysis system and a surface EMG
      system to record, in 10 healthy subjects, the NWR in eight upper limb muscles and
      the corresponding mechanical response in two experimental conditions: rest and
      movement (reaching for, picking up, and moving a cylinder). The NWR was elicited
      through stimulation of the index finger with trains of pulses delivered at
      multiples of the pain threshold (PT). We correlated movement types (reach-to
      grasp, grasp-and-lift), movement phases (acceleration, deceleration), and muscle
      activity types (shortening, lengthening, isometric) with the presence/absence of
      the NWR (reflex-muscle pattern), with NWR size values, and with the mechanical
      responses. At rest, when the stimulus was delivered at 4x PT, the NWR was
      present, in all muscles, in >90% of trials, and the mechanical response consisted
      of wrist adduction, elbow flexion, and shoulder anteflexion. At this stimulus
      intensity, during movement, the reflex-muscle pattern, reflex size, and
      mechanical responses were closely modulated by movement type and phase and by
      muscle activity type. We did not find, during movement, significant correlations
      with the level of EMG background activity. Our findings suggest that a complex
      functional adaptation of the spinal cord plays a role in modulating the NWR in
      the transition from rest to movement and during voluntary arm movement freely
      performed in three-dimensional space. Study of the upper limb NWR may provide a
      window onto the spinal neural control mechanisms operating during movement.

PMID- 16571759
TI  - Improved long-term potentiation and memory in young tau-P301L transgenic mice
      before onset of hyperphosphorylation and tauopathy.
AB  - The microtubule binding protein tau is implicated in neurodegenerative
      tauopathies, including frontotemporal dementia (FTD) with Parkinsonism caused by
      diverse mutations in the tau gene. Hyperphosphorylation of tau is considered
      crucial in the age-related formation of neurofibrillary tangles (NFTs)
      correlating well with neurotoxicity and cognitive defects. Transgenic mice
      expressing FTD mutant tau-P301L recapitulate the human pathology with progressive
      neuronal impairment and accumulation of NFT. Here, we studied tau-P301L mice for
      parameters of learning and memory at a young age, before hyperphosphorylation and
      tauopathy were apparent. Unexpectedly, in young tau-P301L mice, increased long
      term potentiation in the dentate gyrus was observed in parallel with improved
      cognitive performance in object recognition tests. Neither tau phosphorylation,
      neurogenesis, nor other morphological parameters that were analyzed could account
      for these cognitive changes. The data demonstrate that learning and memory
      processes in the hippocampus of young tau-P301L mice are not impaired and
      actually improved in the absence of marked phosphorylation of human tau. We
      conclude that protein tau plays an important beneficial role in normal neuronal
      processes of hippocampal memory, and conversely, that not tau mutations per se,
      but the ensuing hyperphosphorylation must be critical for cognitive decline in
      tauopathies.

PMID- 16571760
TI  - A 3-synapse positive feedback loop regulates the excitability of an interneuron
      critical for sensitization in the leech.
AB  - Sensitization of reflexive shortening in the leech has been linked to serotonin
      (5-HT)-induced changes in the excitability of a single interneuron, the S cell.
      This neuron is necessary for sensitization and complete dishabituation of
      reflexive shortening, during which it contributes to the sensory-motor reflex.
      The S cell does not contain 5-HT, which is released primarily from the Retzius
      (R) cells, whose firing enhances S-cell excitability. Here, we show that the S
      cell excites the R cells, mainly via a fast disynaptic pathway in which the first
      synapse is the electrical junction between the S cell and the coupling
      interneurons, and the second synapse is a glutamatergic synapse of the coupling
      interneurons onto the R cells. The S cell-triggered excitatory postsynaptic
      potential in the R cell diminishes and nearly disappears in elevated
      concentrations of divalent cations because the coupling interneurons become
      inexcitable under these conditions. Serotonin released from the R cells feeds
      back on the S cell and increases its excitability by activating a 5-HT7-like
      receptor; 5-methoxytryptamine (5-MeOT; 10 microM) mimics the effects of 5-HT on S
      cell excitability, and effects of both 5-HT and 5-MeOT are blocked by pimozide
      (10 microM) and SB-269970 [(R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine
      1-sulfonyl)phenol] (5 microM). This feedback loop may be critical for the full
      expression of sensitization of reflexive shortening.

PMID- 16571761
TI  - The neural site of attention matches the spatial scale of perception.
AB  - What is the neural locus of visual attention? Here we show that the locus is not
      fixed but instead changes rapidly to match the spatial scale of task-relevant
      information in the current scene. To accomplish this, we obtained electrical,
      magnetic, and hemodynamic measures of attention from human subjects while they
      detected large-scale or small-scale targets within multiscale stimulus patterns.
      Subjects did not know the scale of the target before stimulus onset, and yet the
      neural locus of attention-related activity between 250 and 300 ms varied
      according to the scale of the target. Specifically, maximal attention-related
      activity spread from a high-level, relatively anterior visual area (the lateral
      occipital complex) for large-scale targets to include a lower-level, more
      posterior area (visual area V4) for small-scale targets. This rapid change
      indicates that the neural locus of attention in visual cortex is not static but
      is instead determined rapidly and dynamically by means of an interaction between
      top-down task information and local information about the current visual input.

PMID- 16571763
TI  - A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia
      after spinal nerve ligation: respective roles of JNK activation in primary
      sensory neurons and spinal astrocytes for neuropathic pain development and
      maintenance.
AB  - Optimal management of neuropathic pain is a major clinical challenge. We
      investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain
      produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and
      persistent (>21 d) activation of JNK, in particular JNK1, in GFAP-expressing
      astrocytes in the spinal cord. In contrast, p38 mitogen-activated protein kinase
      activation was found in spinal microglia after SNL, which had fallen to near
      basal level by 21 d. Intrathecal infusion of a JNK peptide inhibitor, D-JNKI-1,
      did not affect normal pain responses but potently prevented and reversed SNL
      induced mechanical allodynia, a major symptom of neuropathic pain. Intrathecal D
      JNKI-1 also suppressed SNL-induced phosphorylation of the JNK substrate, c-Jun,
      in spinal astrocytes. However, SNL-induced upregulation of GFAP was not
      attenuated by spinal D-JNKI-1 infusion. Furthermore, SNL induced a rapid (<12 h)
      but transient activation of JNK in the L5 (injured) but not L4 (intact) DRG. JNK
      activation in the DRG was mainly found in small-sized C-fiber neurons. Infusion
      of D-JNKI-1 into the L5 DRG prevented but did not reverse SNL-induced mechanical
      allodynia. Finally, intrathecal administration of an astroglial toxin, l-alpha
      aminoadipate, reversed mechanical allodynia. Our data suggest that JNK activation
      in the DRG and spinal cord play distinct roles in regulating the development and
      maintenance of neuropathic pain, respectively, and that spinal astrocytes
      contribute importantly to the persistence of mechanical allodynia. Targeting the
      JNK pathway in spinal astroglia may present a new and efficient way to treat
      neuropathic pain symptoms.

PMID- 16571764
TI  - The different effects on recognition memory of perirhinal kainate and NMDA
      glutamate receptor antagonism: implications for underlying plasticity mechanisms.
AB  - To investigate the involvement of different types of glutamate receptors in
      recognition memory, selective antagonists of NMDA and kainate receptors were
      locally infused into the perirhinal cortex of the rat temporal lobe. Such
      infusion of a selective kainate receptor antagonist produced an unusual pattern
      of recognition memory impairment: amnesia after a short (20 min) but not a long
      (24 h) delay. In contrast, antagonism of perirhinal NMDA glutamate receptors by
      locally infused AP-5 (2-amino-5-phosphonopentanoic acid) impaired recognition
      memory after the long but not the short delay. For both drugs, impairment was
      found when the drug was present during acquisition but not when it was present
      during retrieval. Experiments in vitro indicate that selective antagonism of NMDA
      receptors containing NR2A subunits blocks perirhinal long-term potentiation
      (LTP), whereas antagonism of NMDA receptors containing NR2B subunits blocks long
      term depression (LTD). However, recognition memory after a 24 h delay was
      impaired only when both an NR2A and an NR2B antagonist were infused together, not
      when either was infused separately. These results establish that kainate
      receptors have a role in recognition memory that is distinct from that of NMDA
      receptors, that there must be at least two independent underlying memory
      mechanisms in the infused region, that this region and no other is necessary for
      both short-term and long-term familiarity discrimination, and that perirhinal
      dependent long-term recognition memory does not rely solely on processes used in
      NMDA-dependent LTP or LTD (although it might be independently supported by
      components of each type of process with one substituting for the other).

PMID- 16571762
TI  - Nuclear factor kappaB deficiency is associated with auditory nerve degeneration
      and increased noise-induced hearing loss.
AB  - Degeneration of the spiral ganglion neurons (SGNs) of the auditory nerve occurs
      with age and in response to acoustic injury. Histopathological observations
      suggest that the neural degeneration often begins with an excitotoxic process
      affecting the afferent dendrites under the inner hair cells (IHCs), however,
      little is known about the sequence of cellular or molecular events mediating this
      excitotoxicity. Nuclear factor kappaB (NFkappaB) is a transcription factor
      involved in regulating inflammatory responses and apoptosis in many cell types.
      NFkappaB is also associated with intracellular calcium regulation, an important
      factor in neuronal excitotoxicity. Here, we provide evidence that NFkappaB can
      play a central role in the degeneration of SGNs. Mice lacking the p50 subunit of
      NFkappaB (p50(-/-) mice) showed an accelerated hearing loss with age that was
      highly associated with an exacerbated excitotoxic-like damage in afferent
      dendrites under IHCs and an accelerated loss of SGNs. Also, as evidenced by
      immunostaining intensity, calcium-buffering proteins were significantly elevated
      in SGNs of the p50(-/-) mice. Finally, the knock-out mice exhibited an increased
      sensitivity to low-level noise exposure. The accelerated hearing loss and neural
      degeneration with age in the p50(-/-) mice occurred in the absence of concomitant
      hair cell loss and decline of the endocochlear potential. These results indicate
      that NFkappaB activity plays an important role in protecting the primary auditory
      neurons from excitotoxic damage and age-related degeneration. A possible
      mechanism underlying this protection is that the NFkappaB activity may help to
      maintain calcium homeostasis in SGNs.

PMID- 16571765
TI  - Competition between feedback loops underlies normal and pathological dynamics in
      the basal ganglia.
AB  - Experiments performed in normal animals suggest that the basal ganglia (BG) are
      crucial in motor program selection. BG are also involved in movement disorders.
      In particular, BG neuronal activity in parkinsonian animals and patients is more
      oscillatory and more synchronous than in normal individuals. We propose a new
      model for the function and dysfunction of the motor part of BG. We hypothesize
      that the striatum, the subthalamic nucleus, the internal pallidum (GPi), the
      thalamus, and the cortex are involved in closed feedback loops. The direct
      (cortex-striatum-GPi-thalamus-cortex) and the hyperdirect loops (cortex
      subthalamic nucleus-GPi-thalamus-cortex), which have different polarities, play a
      key role in the model. We show that the competition between these two loops
      provides the BG-cortex system with the ability to perform motor program
      selection. Under the assumption that dopamine potentiates corticostriatal
      synaptic transmission, we demonstrate that, in our model, moderate dopamine
      depletion leads to a complete loss of action selection ability. High depletion
      can lead to synchronous oscillations. These modifications of the network
      dynamical state stem from an imbalance between the feedback in the direct and
      hyperdirect loops when dopamine is depleted. Our model predicts that the loss of
      selection ability occurs before the appearance of oscillations, suggesting that
      Parkinson's disease motor impairments are not directly related to abnormal
      oscillatory activity. Another major prediction of our model is that synchronous
      oscillations driven by the hyperdirect loop appear in BG after inactivation of
      the striatum.

PMID- 16571766
TI  - Different neural substrates mediate cocaine seeking after abstinence versus
      extinction training: a critical role for the dorsolateral caudate-putamen.
AB  - Cue-induced reinstatement of extinguished drug seeking is a preclinical model of
      relapse. However, relapse typically occurs after abstinence rather than explicit
      extinction training. We show that inactivation of the dorsolateral caudate
      putamen, but not other structures previously implicated in reinstatement,
      attenuates cocaine seeking after abstinence. This suggests that there is limited
      overlap in the substrates of cocaine seeking after abstinence versus extinction,
      and that habit learning exerts greater control over drug seeking than regions
      implicated in stimulus-reward associations.

PMID- 16571767
TI  - Hypothalamic deep brain stimulation in positron emission tomography.
AB  - Recently, functional imaging data have underscored the crucial role the
      hypothalamus plays in cluster headache, one of the most severe forms of primary
      headache. This prompted the application of hypothalamic deep brain stimulation.
      Yet, it is not apparent how stimulation of an area that is thought to act as a
      pace-maker for acute headache attacks is able to prevent these attacks from
      occurring. We addressed this issue by examining 10 operated chronic cluster
      headache patients, using H2(15O)-positron emission tomography and alternately
      switching the hypothalamic stimulator on and off. The stimulation induced
      activation in the ipsilateral hypothalamic gray (the site of the stimulator tip),
      the ipsilateral thalamus, somatosensory cortex and praecuneus, the anterior
      cingulate cortex, and the ipsilateral trigeminal nucleus and ganglion. We
      additionally observed deactivation in the middle temporal gyrus, posterior
      cingulate cortex, and contralateral anterior insula. Both activation and
      deactivation are situated in cerebral structures belonging to neuronal circuits
      usually activated in pain transmission and notably in acute cluster headache
      attacks. Our data argue against an unspecific antinociceptive effect or pure
      inhibition of hypothalamic activity. Instead, the data suggest a hitherto
      unrecognized functional modulation of the pain processing network as the mode of
      action of hypothalamic deep brain stimulation in cluster headache.

PMID- 16571768
TI  - Stabilization of axon branch dynamics by synaptic maturation.
AB  - The developmental refinement of topographic projections in the brain is reflected
      in the dynamic sculpting of axonal arbors that takes place as connections between
      CNS structures form and mature. To examine the role of synaptogenesis and
      synaptic maturation in the structural development of axonal projections during
      the formation of the topographic retinotectal projection, we coexpressed
      cytosolic fluorescent protein (FP) and FP-tagged synaptophysin (SYP) in small
      numbers of retinal ganglion cells in living albino Xenopus laevis tadpoles to
      reveal the distribution and dynamics of presynaptic sites within labeled
      retinotectal axons. Two-photon time-lapse observations followed by quantitative
      analysis of tagged SYP levels at individual synapses demonstrated the time course
      of synaptogenesis: increases in presynaptic punctum intensity are detectable
      within minutes of punctum emergence and continue over many hours. Puncta
      lifetimes correlate with their intensities. Furthermore, we found that axon arbor
      dynamics are affected by synaptic contacts. Axon branches retract past faintly
      labeled puncta but are locally stabilized at intensely labeled SYP puncta. Visual
      stimulation for 4 h enhanced the stability of the arbor at intense presynaptic
      puncta while concurrently inducing the retraction of exploratory branches with
      only faintly labeled or no synaptic sites.

PMID- 16571769
TI  - Evidence from in vivo imaging that synaptogenesis guides the growth and branching
      of axonal arbors by two distinct mechanisms.
AB  - To explore the relationship between axon arbor growth and synaptogenesis,
      developing retinal ganglion cell (RGC) axon arbors in zebrafish optic tectum were
      imaged in vivo at high temporal and spatial resolution using two-photon
      microscopy. Individual RGC axons were dually labeled by expression of a cytosolic
      red fluorescent protein (DsRed Express) to mark arbor structure and a fusion of
      the synaptic vesicle protein synaptophysin with green fluorescent protein
      (Syp:GFP) to mark presynaptic vesicles. Analysis of time-lapse sequences acquired
      at 10 min intervals revealed unexpectedly rapid kinetics of both axon branch and
      vesicle cluster turnover. Nascent axonal branches exhibited short average
      lifetimes of 19 min, and only 17% of newly extended axonal processes persisted
      for periods exceeding 3 h. The majority (70%) of Syp:GFP puncta formed on newly
      extended axonal processes. Syp:GFP puncta also exhibited short average lifetimes
      of 30 min, and only 34% of puncta were stabilized for periods exceeding 3 h.
      Moreover, strongly correlated dynamics of Syp:GFP puncta and branch structure
      suggest that synaptogenesis exerts strong influences on both the extension and
      the selective stabilization of nascent branches. First, new branches form almost
      exclusively at newly formed Syp:GFP puncta. Second, stabilized nascent branches
      invariably bear Syp:GFP puncta, and the detailed dynamics of branch retraction
      suggest strongly that nascent synapses can act at branch tips to arrest
      retraction. These observations thus provide evidence that synaptogenesis guides
      axon arbor growth by first promoting initial branch extension and second by
      selective branch stabilization.

PMID- 16571770
TI  - Movement intention is better predicted than attention in the posterior parietal
      cortex.
AB  - We decoded on a trial-by-trial basis the location of visual targets, as a marker
      of the locus of attention, and intentions to reach and to saccade in different
      directions using the activity of neurons in the posterior parietal cortex of two
      monkeys. Predictions of target locations were significantly worse than
      predictions of movement plans for the same target locations. Moreover, neural
      signals in the parietal reach region (PRR) gave better predictions of reaches
      than saccades, whereas signals in the lateral intraparietal area (LIP) gave
      better predictions of saccades than reaches. Taking together the activity of both
      areas, the prediction of either movement in all directions became nearly perfect.
      These results cannot be explained in terms of an attention effect and support the
      idea of two segregated populations in the posterior parietal cortex, PRR and LIP,
      that are involved in different movement plans.

PMID- 16571771
TI  - IFN-beta-induced SOCS-1 negatively regulates CD40 gene expression in macrophages
      and microglia.
AB  - Costimulation between T cells and antigen-presenting cells is required for
      adaptive immune responses. CD40, a costimulatory molecule, is expressed in
      macrophages and microglia. The aberrant expression of CD40 is involved in human
      diseases including multiple sclerosis, rheumatoid arthritis, and Alzheimer's
      disease. CD40 expression is induced by a variety of stimuli, including IFN-gamma
      and lipopolysaccharide (LPS). In this study, we describe the molecular basis by
      which IFN-beta, a cytokine with immunomodulatory properties, regulates CD40 gene
      expression. IFN-beta induces CD40 expression in macrophages and microglia at the
      transcriptional level, and GAS elements in the CD40 promoter are required for IFN
      beta-induced CD40 promoter activity. The critical role of signal transducers and
      activators of transcription-1alpha (STAT-1alpha) in this response was confirmed
      by utilizing primary microglia from STAT-1alpha deficient mice. IFN-beta induces
      suppressor of cytokine signaling-1 (SOCS-1) gene expression, which inhibits
      cytokine signaling by inhibiting activation of STAT proteins. The ectopic
      expression of SOCS-1 abrogates IFN-beta-mediated STAT-1alpha activation and
      inhibits IFN-beta-induced CD40 expression. IFN-beta-induced recruitment of STAT
      1alpha and RNA Pol II and permissive histone modifications on the CD40 promoter
      are also inhibited by SOCS-1 overexpression. These novel results indicate that
      IFN-beta-induced SOCS-1 plays an important role in the negative regulation of IFN
      beta-induced CD40 gene expression.

PMID- 16571772
TI  - In vivo overexpression of Flt3 ligand expands and activates murine spleen natural
      killer dendritic cells.
AB  - Natural killer dendritic cells (NKDC) are a unique class of murine immune cells
      that possess the characteristics of both natural killer (NK) cells and dendritic
      cells (DC). Because NKDC are able to secrete IFN-gamma, directly lyse tumor
      cells, and present antigen to naive T cells, they have immunotherapeutic
      potential. The relative paucity of NKDC, however, impedes their detailed study.
      We have found that in vivo, overexpression of the hematopoietic cytokine Flt3
      ligand (Flt3L) expands NKDC in various organs from 2-18 fold. Flt3L expanded
      splenic NKDC retain the ability to lyse tumor cells and become considerably more
      potent at activating naive allogeneic and antigen-specific T cells. Compared to
      normal splenic NKDC, Flt3L-expanded splenic NKDC have a more mature phenotype, a
      slightly increased ability to capture and process antigen, and a similar cytokine
      profile. In vivo, we found that Flt3L-expanded splenic NKDC are more effective
      than normal splenic NKDC in stimulating antigen-specific CD8 T cells.
      Additionally, we show that NKDC are able to cross-present antigen in vivo. The
      ability to expand NKDC in vivo using Flt3L will facilitate further analysis of
      their unique biology. Moreover, Flt3L-expanded NKDC may have enhanced
      immunotherapeutic potential, given their increased ability to stimulate T cells.

PMID- 16571773
TI  - Brain mitochondrial defects amplify intracellular [Ca2+] rise and
      neurodegeneration but not Ca2+ entry during NMDA receptor activation.
AB  - According to the "indirect" excitotoxicity hypothesis, mitochondrial defects
      increase Ca2+ entry into neurons by rendering NMDA-R hypersensitive to glutamate.
      We tested this hypothesis by investigating in the rat striatum and cultured
      striatal cells how partial mitochondrial complex II inhibition produced by 3
      nitropropionic acid (3NP) modifies the toxicity of the NMDA-R agonist quinolinate
      (QA). We showed that nontoxic 3NP treatment, leading to partial inhibition of
      complex II activity, greatly exacerbated striatal degeneration produced by
      slightly toxic QA treatment through an "all-or-nothing" process. The potentiation
      of QA-induced cell death by 3NP was associated with increased calpain activity
      and massive calpain-mediated cleavage of several postsynaptic proteins,
      suggesting major neuronal Ca2+ deregulation in the striatum. However, Ca2+
      anomalies probably do not result from NMDA-R hypersensitivity. Indeed, brain
      imaging experiments using [(18)F]fluorodeoxyglucose indirectly showed that 3NP
      did not increase QA-induced ionic perturbations at the striatal glutamatergic
      synapses in vivo. Consistent with this, the exacerbation of QA toxicity by 3NP
      was not related to an increase in the QA-induced entry of 45Ca2+ into striatal
      neurons. The present results demonstrate that the potentiation of NMDA-R-mediated
      excitotoxicity by mitochondrial defects involves primarily intracellular Ca2+
      deregulation, in the absence of NMDA-R hypersensitivity.

PMID- 16571774
TI  - Changes of endoplasmic reticulum chaperone complexes, redox state, and impaired
      protein disulfide reductase activity in misfolding alpha1-antitrypsin transgenic
      mice.
AB  - Alpha1-antitrypsin (AAT) deficiency is characterized by the accumulation of the
      misfolded mutant, Z form of alpha1-antitrypsin (PiZ) inside the lumen of the
      hepatic endoplasmic reticulum (ER). Both human patients and PiZ transgenic mice
      have similar symptoms of hepatic failure culminating in cirrhosis and
      hepatocellular carcinoma. The involvement of molecular chaperones, as well as the
      relevance of oxidative stress in this disease is not characterized well yet.
      Here, we show that, in the PiZ transgenic mice, the 58-kDa protein disulfide
      isomerase (PDI), the most important oxidoreductase and chaperone of the
      endoplasmic reticulum, is in a complex with PiZ, which is accompanied by a
      decrease of protein disulfide reductase activity of the ER. PiZ transgenic mice
      have a shift toward a more reduced ER environment and an elevation of cytoplasmic
      chaperones and antioxidant enzymes. Our data suggest that lower availability of
      PDI and a decreased protein disulfide reductase activity of the ER along with a
      cytoplasmic stress may contribute to the toxic effects of PiZ aggregation.

PMID- 16571775
TI  - Lysophospholipid transacetylase in the regulation of PAF levels in human
      monocytes and macrophages.
AB  - The transacetylase (TA), reported to be identical to platelet-activating factor
      (PAF) acetylhydrolase (II), is a multifunctional enzyme with three catalytic
      activities: lysophospholipid transacetylase (TA(L)), sphingosine transacetylase
      (TA(S)), and acetylhydrolase (AH). We report that TA(L) activity participates in
      the control of PAF levels in monocytes and macrophages and that its regulation
      differs in these two types of cells. In monocytes, LPS or granulocyte-macrophage
      colony-stimulating factor (GM-CSF) specifically increased the TA(L) activity.
      Western blot analysis and enzyme assays on immunoprecipitates revealed that the
      increased activity can be ascribed to PAF-AH (II) and that both translocation
      from cytosol to membranes and p38/ERKs-mediated phosphorylation regulate the
      enzyme activation. Instead, in macrophages differentiated in vitro from monocytes
      by incubation with FCS, an increase of both TA(L) and AH activities was observed.
      Moreover, activation of ERKs and p38 MAP kinase was not required for the up
      regulation of PAF-AH (II) in differentiated macrophages. The differences observed
      in macrophages as compared to monocytes can be explained by 1) p38/ERKs
      independent phosphorylation of PAF-AH (II) and 2) appearance of plasma PAF-AH in
      the course of macrophage differentiation.

PMID- 16571777
TI  - G-CSF administration after myocardial infarction in mice attenuates late ischemic
      cardiomyopathy by enhanced arteriogenesis.
AB  - Granulocyte-colony stimulating factor (G-CSF) has been shown to improve cardiac
      function after myocardial infarction (MI) by bone marrow cell mobilization and by
      protecting cardiomyocytes from apoptotic cell death. However, its role in
      collateral artery growth (arteriogenesis) has not been elucidated. Here, we
      investigated the effect of G-CSF on arteriolar growth and cardiac function in a
      murine MI model. Mice were treated with G-CSF (100 microg/kg/day) directly after
      MI for 5 consecutive days. G-CSF application resulted in a significant increase
      of circulating mononuclear cells expressing stem cell markers. Arterioles in the
      border zone of infarcted myocardium showed an increased expression of ICAM-1
      accompanied by an accumulation of bone marrow derived cells and a pronounced
      proliferation of endothelial and smooth muscle cells. Histology of G-CSF treated
      mice revealed a lower amount of granulation tissue (67.8 vs. 84.4%) associated
      with a subsequent reduction in free LV wall thinning and scar extension (23.1 vs.
      30.8% of LV). Furthermore, G-CSF treated animals showed a significant improvement
      of post-MI survival (68.8 vs. 46.2%). Pressure-volume relations revealed a
      partially restored myocardial function at day 30 (EF: 32.5 vs. 17.2%). Our
      results demonstrate that G-CSF administration after MI stimulates arteriogenesis
      and attenuates ischemic cardiomyopathy after MI.

PMID- 16571776
TI  - Inhibition of endothelial cell proliferation by Notch1 signaling is mediated by
      repressing MAPK and PI3K/Akt pathways and requires MAML1.
AB  - The requirement for Notch signaling in vasculogenesis and angiogenesis is well
      documented. In a previous study, we showed that activation of the Notch pathway
      in endothelial cells induces differentiation-associated growth arrest; however,
      the underlying mechanism remains to be elucidated. Here, we show that activation
      of the Notch pathway by either stimulation of cell surface Notch receptors with
      crosslinked soluble delta-like 4 (sDll4)/Jagged1 (sJag1) or constitutive
      expression of the Notch1 intracellular domain (N(IC)) suppresses endothelial cell
      proliferation. This suppression is mediated by the mitogen-activated protein
      kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. Following
      Notch1 activation, both pathways were suppressed in endothelial cells, and
      alterations in MAPK or PI3K/Akt pathway activity reversed Notch1-induced growth
      inhibition. Furthermore, we found the effect of Notch1 on endothelial cells to
      require Mastermind-like (MAML). Overexpression of a dominant-negative mutant of
      MAML1 antagonized the effects of activated Notch1 on the MAPK and PI3K/Akt
      pathways. Ectopic expression of Hairy/Enhancer of Split 1 (HES1) consistently
      reproduced the inhibitory effect of N(IC) on endothelial cell proliferation.
      Together, our data demonstrate that the Notch/MAML-HES signaling cascade can
      regulate both MAPK and PI3K/Akt pathways, which suggests a molecular mechanism
      for the inhibitory effect of Notch signaling on endothelial cell proliferation.

PMID- 16571778
TI  - Transcriptional regulation of CD38 expression by tumor necrosis factor-alpha in
      human airway smooth muscle cells: role of NF-kappaB and sensitivity to
      glucocorticoids.
AB  - The transmembrane glycoprotein CD38 catalyzes the synthesis of the calcium
      mobilizing molecule cyclic ADP-ribose from NAD. In human airway smooth muscle
      (HASM) cells, the expression and function of CD38 are augmented by the
      inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), leading to
      increased intracellular calcium response to agonists. A glucocorticoid response
      element in the CD38 gene has been computationally described, providing evidence
      for transcriptional regulation of its expression. In the present study, we
      investigated the effects of dexamethasone, a glucocorticoid, on CD38 expression
      and ADP-ribosyl cyclase activity in HASM cells stimulated with TNF-alpha. In HASM
      cells, TNF-alpha augmented CD38 expression and ADP-ribosyl cyclase activity,
      which were attenuated by dexamethasone. TNF-alpha increased NF-kappaB expression
      and its activation, and dexamethasone partially reversed these effects. TNF-alpha
      increased the expression of IkappaBalpha, and dexamethasone increased it further.
      An inhibitor of NF-kappaB activation or transfection of cells with IkappaB
      mutants decreased TNF-alpha-induced CD38 expression. The results indicate that
      TNF-alpha-induced CD38 expression involves NF-kappaB expression and its
      activation and dexamethasone inhibits CD38 expression through NF-kappaB-dependent
      and -independent mechanisms.

PMID- 16571779
TI  - Transcriptional up-regulation of MMP12 and MMP13 by asbestos occurs via a
      PKCdelta-dependent pathway in murine lung.
AB  - Asbestos is a known inflammatory, carcinogenic, and fibrotic agent, but the
      mechanisms leading to asbestos-induced lung diseases are unclear. Using a murine
      inhalation model of fibrogenesis, we show that asbestos causes significant
      increases in mRNA levels of lung matrix metalloproteinases (MMPs 12 and 13) and
      tissue inhibitor of metalloproteinases (TIMP1), as well as increased activities
      of MMP 2, 9, and 12 in bronchoalveolar lavage fluids (BALF). Asbestos-exposed
      PKCdelta knockout (PKCdelta-/-) mice exhibited decreased expression of lung MMP12
      and MMP13 compared with asbestos-exposed wild-type mice. Studies using small
      molecule inhibitors in murine alveolar epithelial type II cells (C10) and primary
      lung fibroblasts confirmed that asbestos transcriptionally up-regulates MMPs via
      an EGFR (or other growth factor receptors)/PI3K/PKCdelta/ERK1/2 pathway.
      Moreover, use of a broad-spectrum MMP inhibitor showed that MMPs play an
      important role in further enhancing asbestos-induced signaling events by
      activating EGFR. These data reveal a potentially important link between asbestos
      signaling and integrity of the extracellular matrix (ECM) that likely contributes
      to asbestos-induced lung remodeling and diseases.

PMID- 16571780
TI  - Transforming growth factor-beta1 enhances the antifibrinolytic and prothrombotic
      state of growing endothelial cells in a cell cycle-specific manner.
AB  - Cell cycle-dependent modulation of protein expression may influence the balance
      of antithrombotic and prothrombotic properties of endothelial cells. In the
      present study, we examined the regulation of prothrombotic and antithrombotic
      molecules by transforming growth factor-beta1 (TGF-beta1) during distinct phases
      of the cell cycle in human umbilical vein endothelial cells. In the absence of
      TGF-beta1, the expression of thrombomodulin, the plasminogen activators u-PA and
      t-PA, and their inhibitor PAI-1 was significantly increased in the S/G2 compared
      to the G1 phase. Treatment of endothelial cells with TGF-beta1, however, resulted
      in elevated expression of PAI-1 specifically in the S/G2 phase, while t-PA and u
      PA increased to the same extent in both the G1 and S/G2 phase. These findings
      demonstrate that the expression of a subset of hemostatically relevant proteins
      is regulated during endothelial cell cycle and that TGF-beta1 can differentially
      modulate cell cycle-controlled protein expression.

PMID- 16571781
TI  - Increasing cannabinoid levels by pharmacological and genetic manipulation delay
      disease progression in SOD1 mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      characterized by the selective loss of motoneurons in the spinal cord, brain
      stem, and motor cortex. However, despite intensive research, an effective
      treatment for this disease remains elusive. In this study we show that treatment
      of postsymptomatic, 90-day-old SOD1G93A mice with a synthetic cannabinoid,
      WIN55,212-2, significantly delays disease progression. Furthermore, genetic
      ablation of the Faah enzyme, which results in raised levels of the
      endocannabinoid anandamide, prevented the appearance of disease signs in 90-day
      old SOD1G93A mice. Surprisingly, elevation of cannabinoid levels with either
      WIN55,212-2 or Faah ablation had no effect on life span. Ablation of the CB1
      receptor, in contrast, had no effect on disease onset in SOD1(G93A) mice but
      significantly extended life span. Together these results show that cannabinoids
      have significant neuroprotective effects in this model of ALS and suggest that
      these beneficial effects may be mediated by non-CB1 receptor mechanisms.

PMID- 16571782
TI  - Spironolactone prevents diabetic nephropathy through an anti-inflammatory
      mechanism in type 2 diabetic rats.
AB  - Aldosterone induces myocardial fibrosis and vascular inflammation via
      proinflammatory and profibrotic cytokines. The effect of spironolactone on renal
      inflammation and renal function was investigated in type 2 diabetic rats. For
      define the molecular mechanism of spironolactone, the effect of spironolactone on
      the synthesis of monocyte chemotactic peptide-1 (MCP-1) and its upstream
      transcription factor, NF-kappaB, was evaluated in cultured mesangial cells and
      proximal tubular cells. There were no changes in blood glucose concentration or
      BP after spironolactone treatment. Spironolactone treatment significantly reduced
      urinary albumin excretion and ameliorated glomerulosclerosis. Urinary levels of
      MCP-1 were significantly increased concurrently with renal expression of MCP-1,
      macrophage migration inhibitory factor, and macrophage infiltration.
      Spironolactone treatment significantly inhibited urinary excretion of MCP-1 as
      well as renal MCP-1 and migration inhibitory factor expression and macrophage
      infiltration. In addition, aldosterone induced upregulation of MCP-1 expression
      and NF-kappaB transcriptional activity in cultured cells, and spironolactone
      reduced both NF-kappaB activation and MCP-1 synthesis. Furthermore, NF-kappaB
      inhibition abolished aldosterone-induced MCP-1 production. Overall, these
      findings suggest that aldosterone-induced NF-kappaB activation leads to
      activation of proinflammatory cytokines, ultimately leading to renal injury in
      this model. These data suggest that mineralocorticoid blockade may be a potential
      therapeutic target in diabetic nephropathy.

PMID- 16571783
TI  - Distal colonic K(+) secretion occurs via BK channels.
AB  - K(+) secretion in the kidney and distal colon is a main determinant of K(+)
      homeostasis. This study investigated the identity of the relevant luminal
      secretory K(+) ion channel in distal colon. An Ussing chamber was used to measure
      ion transport in the recently generated BK channel-deficient (BK(-/-)) mice. BK(
      /-) mice display a significant colonic epithelial phenotype with (1) lack of
      Ba(2+)-sensitive resting K(+) secretion, (2) absence of K(+) secretion stimulated
      by luminal P2Y(2) and P2Y(4) receptors, (3) absence of luminal Ca(2+) ionophore
      (A23187)-stimulated K(+) secretion, (4) reduced K(+) and increased Na(+) contents
      in feces, and (5) an increased colonic Na(+) absorption. In contrast, resting and
      uridine triphosphate (UTP)-stimulated K(+) secretion was not altered in mice that
      were deficient for the intermediate conductance Ca(2+)-activated K(+) channel
      SK4. BK channels localize to the luminal membrane of crypt, and reverse
      transcription-PCR results confirm the expression of the BK channel alpha-subunit
      in isolated distal colonic crypts. It is concluded that BK channels are the
      responsible K(+) channels for resting and stimulated Ca(2+)-activated K(+)
      secretion in mouse distal colon.

PMID- 16571784
TI  - Differential expression of the intermediate filament protein nestin during renal
      development and its localization in adult podocytes.
AB  - Nestin, an intermediate filament protein, is widely used as stem cell marker.
      Nestin has been shown to interact with other cytoskeleton proteins, suggesting a
      role in regulating cellular cytoskeletal structure. These studies examined renal
      nestin localization and developmental expression in mice. In developing kidney,
      anti-nestin antibody revealed strong immunoreactivity in vascular cleft of the S
      shaped body and vascular tuft of capillary loop-stage glomerulus. The nestin
      positive structures also were labeled by endothelial cell markers FLK1 and CD31
      in immature glomeruli. Nestin was not detected in epithelial cells of immature
      glomeruli. In contrast, in mature glomerular, nestin immunoreactivity was
      observed only outside laminin-positive glomerular basement membrane, and co
      localized with nephrin, consistent with podocyte nestin expression. In adult
      kidney, podocytes were the only cells that exhibited persistent nestin
      expression. Nestin was not detected in ureteric bud and its derivatives
      throughout renal development. Cell lineage studies, using a nestin promoter
      driven Cre mouse and a ROSA26 reporter mouse, showed a strong beta-galactosidase
      activity in intermediate mesoderm in an embryonic day 10 embryo and all of the
      structures except those that were derived from ureteric bud in embryonic kidney
      through adult kidney. These studies show that nestin is expressed in progenitors
      of glomerular endothelial cells and renal progenitors that are derived from
      metanephric mesenchyme. In the adult kidney, nestin expression is restricted to
      differentiated podocytes, suggesting that nestin could play an important role in
      maintaining the structural integrity of the podocytes.

PMID- 16571785
TI  - Dietary sodium intake regulates the ubiquitin-protein ligase nedd4-2 in the renal
      collecting system.
AB  - The activity of the epithelial sodium (Na(+)) channel (ENaC) in the aldosterone
      sensitive distal nephron (ASDN) needs to be tightly regulated to match urinary
      Na(+) excretion with dietary Na(+) intake. The ubiquitin-protein ligase Nedd4-2,
      which in vitro interacts with ENaC subunits and reduces ENaC cell surface
      abundance and activity by ubiquitylation of the channel, may participate in the
      control of ENaC. This study confirms in vivo by reverse-transcriptase-PCR that
      Nedd4-2 is expressed throughout the nephron and is detectable by immunoblotting
      in kidney extracts. By immunohistochemistry, Nedd4-2 was found to be strongly
      expressed in the ASDN, with low staining intensity in the late distal convoluted
      tubule and early connecting tubule (where apical ENaC is high) and gradually
      increasing detection levels toward the collecting duct (CD; where apical ENaC is
      low). Compared with high-Na(+) diet (5% Na(+)), 2 wk of low-Na(+) diet (0.01%
      Na(+)) drastically reduces Nedd4-2 immunostaining and increases apical ENaC
      abundance in ASDN. Reduced Nedd4-2 immunostaining is not dependent on increased
      apical Na(+) entry in the CD, because it is similarly observed in mice with
      intact and with suppressed apical ENaC activity in the CD. Consistent with a role
      of mineralocorticoid hormones in the long-term regulation of Nedd4-2, 5-d
      treatment of cultured CD (mpkCCD(cl4)) cells with 1 microM aldosterone leads to
      reduction of Nedd4-2 protein expression. It is concluded that Nedd4-2 abundance
      is regulated by Na(+) diet, by a mechanism that likely involves aldosterone. This
      regulation may contribute to adaptation of apical ENaC activity to altered Na(+)
      intake.

PMID- 16571786
TI  - Induction of G2 arrest and binding to cyclophilin A are independent phenotypes of
      human immunodeficiency virus type 1 Vpr.
AB  - Cyclophilin A (CypA) is a member of a family of cellular proteins that share a
      peptidyl prolyl cis-trans isomerase (PPIase) activity. CypA was previously
      reported to be required for the biochemical stability and function (specifically,
      induction of G2 arrest) of the human immunodeficiency virus type 1 (HIV-1)
      protein R (Vpr). In the present study, we examine the role of the Vpr-CypA
      interaction on Vpr-induced G2 arrest. We find that Vpr coimmunoprecipitates with
      CypA and that this interaction is disrupted by substitution of proline-35 of Vpr
      as well as incubation with the CypA inhibitor cyclosporine A (CsA). Surprisingly,
      the presence of CypA or its binding to Vpr is dispensable for the ability of Vpr
      to induce G2 arrest. Vpr expression in CypA-/- cells leads to induction of G2
      arrest in a manner that is indistinguishable from that in CypA+ cells. CsA
      abolished CypA-Vpr binding but had no effect on induction of G2 arrest or Vpr
      steady-state levels. In view of these results, we propose that the interaction
      with CypA is independent of the ability of Vpr to induce cell cycle arrest. The
      interaction between Vpr and CypA is intriguing, and further studies should
      examine its potential effects on other functions of Vpr.

PMID- 16571787
TI  - Role of residues 121 to 124 of vesicular stomatitis virus matrix protein in virus
      assembly and virus-host interaction.
AB  - The recent solution of the crystal structure of a fragment of the vesicular
      stomatitis virus matrix (M) protein suggested that amino acids 121 to 124,
      located on a solvent-exposed loop of the protein, are important for M protein
      self-association and association with membranes. These residues were mutated from
      the hydrophobic AVLA sequence to the polar sequence DKQQ. Expression and
      purification of this mutant from bacteria showed that it was structurally stable
      and that the mutant M protein had self-association kinetics similar to those of
      the wild-type M protein. Analysis of the membrane association of M protein in the
      context of infection with isogenic recombinant viruses showed that both wild-type
      and mutant M proteins associated with membranes to the same extent. Virus
      expressing the mutant M protein did show an approximately threefold-lower binding
      affinity of M protein for nucleocapsid-M complexes. In contrast to the relatively
      minor effects of the M protein mutation on virus assembly, the mutant virus
      exhibited growth restriction in MDBK but not BHK cells, a slower induction of
      apoptosis, and lower viral-protein synthesis. Despite translating less viral
      protein, the mutant virus produced more viral mRNA, showing that the mutant virus
      could not effectively promote viral translation. These results demonstrate that
      the 121-to-124 region of the VSV M protein plays a minor role in virus assembly
      but is involved in virus-host interactions and VSV replication by augmenting
      viral-mRNA translation.

PMID- 16571788
TI  - Evidence for a functional link between uncoating of the human immunodeficiency
      virus type 1 core and nuclear import of the viral preintegration complex.
AB  - Human immunodeficiency virus type 1 (HIV-1) particles begin their replication
      upon fusion with the plasma membrane of target cells and release of the viral
      core into the host cell cytoplasm. Soon thereafter, the viral capsid, which is
      composed of a polymer of the CA protein, disassociates from the internal
      ribonucleoprotein complex. While this disassembly process remains poorly
      understood, the available evidence indicates that proper uncoating of the core is
      a key step in infection. Defects in uncoating most often lead to a failure of the
      virus to undergo reverse transcription, resulting in an inability to form a
      functional viral preintegration complex (PIC). In a previous study, we reported
      that an HIV-1 mutant containing two substitutions in CA (Q63A/67A) was unusual in
      that it was poorly infectious yet synthesized normal levels of viral DNA. Here we
      report that this mutant is impaired for nuclear entry. Quantitative analysis of
      viral DNA synthesis from infected cells by Southern blotting and real-time PCR
      revealed that the Q63A/Q67A mutant is impaired in the synthesis of one-long
      terminal repeat (1-LTR) and 2-LTR circles. Isolation of PICs from acutely
      infected cells revealed that the Q63A/Q67A mutant produces protein-DNA complexes
      similar to wild-type in yield and overall composition, but these PICs contained
      elevated levels of CA and were impaired for integration in vitro. These results
      demonstrate that mutations in CA can have deleterious effects on both nuclear
      targeting and integration, suggesting that these steps in the HIV-1 life cycle
      are dependent on proper uncoating of the viral core.

PMID- 16571789
TI  - Genetic analysis of simian immunodeficiency virus expressed in milk and
      selectively transmitted through breastfeeding.
AB  - To develop effective intervention strategies that prevent breast milk
      transmission of human immunodeficiency virus (HIV), we must understand the
      specific viral properties and mechanisms responsible for infant infection. We
      have used lactating rhesus macaques infected with a pathogenic simian
      immunodeficiency virus (SIV) stock to analyze the viral genotypes expressed in
      plasma and milk throughout the disease course and to identify those variants
      ultimately transmitted to infants through breastfeeding. In these studies we
      observed mother-to-infant transmission of SIV/Delta(B670) by eight females during
      the chronic phase of disease, and we analyzed by heteroduplex tracking assays and
      sequence analysis the distribution and fluctuations in viral genotypes expressed.
      Each female expressed multiple V1 envelope genotypes in milk near the time of
      transmission, while a single genotype was found in each of the infants. Variants
      transmitted to infants were not expressed throughout the maternal disease course
      but were only detected near the time of transmission. The emergence of the
      transmitted genotype in the dam typically occurred in plasma before milk and was
      coincident with increased milk viral loads. Transmitted genotypes tended to be
      longer and more glycosylated and had a less negative charge over the V1 region
      compared to viral genotypes expressed in milk but not transmitted. These
      observations demonstrate that specific viral genotypes are selectively
      transmitted to infants through breastfeeding and support the hypothesis that
      transmission occurs as genotypes adapt for efficient expression in milk.

PMID- 16571790
TI  - Systemic immunization with an ALVAC-HIV-1/protein boost vaccine strategy protects
      rhesus macaques from CD4+ T-cell loss and reduces both systemic and mucosal
      simian-human immunodeficiency virus SHIVKU2 RNA levels.
AB  - Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily via
      the mucosal route, suggesting that HIV-1 vaccines may need to elicit mucosal
      immune responses. Here, we investigated the immunogenicity and relative efficacy
      of systemic immunization with two human ALVAC-HIV-1 recombinant vaccines
      expressing Gag, Pol, and gp120 (vCP250) or Gag, Pol, and gp160 (vCP1420) in a
      prime-boost protocol with their homologous vaccine native Env proteins. The
      relative efficacy was measured against a high-dose mucosal exposure to the
      pathogenic neutralization-resistant variant SHIV(KU2) (simian-human
      immunodeficiency virus). Systemic immunization with both vaccine regimens
      decreased viral load levels not only in blood but unexpectedly also in mucosal
      sites and protected macaques from peripheral CD4+ T-cell loss. This protective
      effect was stronger when the gp120 antigen was included in the vaccine. Inclusion
      of recombinant Tat protein in the boosting phase along with the Env protein did
      not contribute further to the preservation of CD4+ T cells. Thus, systemic
      immunization with ALVAC-HIV-1 vaccine candidates elicits anti-HIV-1 immune
      responses able to contain virus replication also at mucosal sites in macaques.

PMID- 16571791
TI  - Functional mapping of the nucleoprotein of Ebola virus.
AB  - At 739 amino acids, the nucleoprotein (NP) of Ebola virus is the largest
      nucleoprotein of the nonsegmented negative-stranded RNA viruses, and like the NPs
      of other viruses, it plays a central role in virus replication. Huang et al. (Y.
      Huang, L. Xu, Y. Sun, and G. J. Nabel, Mol. Cell 10:307-316, 2002) previously
      demonstrated that NP, together with the minor matrix protein VP24 and polymerase
      cofactor VP35, is necessary and sufficient for the formation of nucleocapsid-like
      structures that are morphologically indistinguishable from those seen in Ebola
      virus-infected cells. They further showed that NP is O glycosylated and
      sialylated and that these modifications are important for interaction between NP
      and VP35. However, little is known about the structure-function relationship of
      Ebola virus NP. Here, we examined the glycosylation of Ebola virus NP and further
      investigated its properties by generating deletion mutants to define the
      region(s) involved in NP-NP interaction (self-assembly), in the formation of
      nucleocapsid-like structures, and in the replication of the viral genome. We were
      unable to identify the types of glycosylation and sialylation, although we did
      confirm that Ebola virus NP was glycosylated. We also determined that the region
      from amino acids 1 to 450 is important for NP-NP interaction (self-assembly). We
      further demonstrated that these amino-terminal 450 residues and the following 150
      residues are required for the formation of nucleocapsid-like structures and for
      viral genome replication. These data advance our understanding of the functional
      region(s) of Ebola virus NP, which in turn should improve our knowledge of the
      Ebola virus life cycle and its extreme pathogenicity.

PMID- 16571792
TI  - U(S)3 and U(S)3.5 protein kinases of herpes simplex virus 1 differ with respect
      to their functions in blocking apoptosis and in virion maturation and egress.
AB  - Previously, we reported that the U(S)3 protein kinase blocks apoptosis, that it
      activates protein kinase A (PKA), that activation of PKA blocks apoptosis in
      cells infected with a U(S)3 deletion mutant, and that an overlapping
      transcriptional unit encodes a truncated kinase designated U(S)3.5. Here, we
      report the properties of the kinases based on comparisons of herpes simplex virus
      and baculoviruses expressing U(S)3 or U(S)3.5 kinase. Specifically, we report the
      following. (i) Both kinases mediate the phosphorylation of HDAC1, HDAC2, and the
      PKA regulatory IIalpha subunit in the absence of other viral proteins. (ii) Both
      enzymes mediate the phosphorylation of largely identical sets of proteins
      carrying the phosphorylation consensus site of PKA, but only U(S)3 blocks
      apoptosis, suggesting that it is U(S)3 and not PKA that is responsible for the
      phosphorylation of the proteins bearing the shared consensus phosphorylation site
      and the antiapoptotic activity. (iii) Both kinases cofractionate with
      mitochondria. Immune depletion of the U(S)3 and U(S)3.5 kinases from the
      cytoplasm removed the kinases from the supernatant fraction, but not from the
      mitochondrial fraction, and therefore, if the antiapoptotic activity of the U(S)3
      kinase is expressed in mitochondria, the localization signal and the
      antiapoptotic functions are located on different parts of the protein. (iv) The
      U(S)3 protein kinase is required for the translocation of virus particles from
      the nucleus. Although the U(L)31 protein is phosphorylated in cells infected with
      the mutant expressing U(S)3.5 kinase, the release of virus particles from nuclei
      was impeded in some cells, suggesting that the U(S)3 kinase affects the
      modification of the nuclear membrane more efficiently than the U(S)3.5 kinase.

PMID- 16571793
TI  - Vpu and Tsg101 regulate intracellular targeting of the human immunodeficiency
      virus type 1 core protein precursor Pr55gag.
AB  - Assembly of human immunodeficiency virus type 1 (HIV-1) is directed by the viral
      core protein Pr55gag. Depending on the cell type, Pr55gag accumulates either at
      the plasma membrane or on late endosomes/multivesicular bodies. Intracellular
      localization of Pr55gag determines the site of virus assembly, but molecular
      mechanisms that define cell surface or endosomal targeting of Pr55gag are poorly
      characterized. We have analyzed targeting of newly synthesized Pr55gag in HeLa H1
      cells by pulse-chase studies and subcellular fractionations. Our results
      indicated that Pr55gag was inserted into the plasma membrane and, when
      coexpressed with the viral accessory protein Vpu, Pr55gag remained at the plasma
      membrane and virions assembled at this site. In contrast, Pr55gag expressed in
      the absence of Vpu was initially inserted into the plasma membrane, but
      subsequently endocytosed, and virus assembly was partially shifted to internal
      membranes. This endocytosis of Pr55gag required the host protein Tsg101. These
      results identified a previously unknown role for Vpu and Tsg101 as regulators for
      the endocytic uptake of Pr55gag and suggested that the site of HIV-1 assembly is
      determined by factors that regulate the endocytosis of Pr55gag.

PMID- 16571795
TI  - Cap-independent translation mechanism of red clover necrotic mosaic virus RNA2
      differs from that of RNA1 and is linked to RNA replication.
AB  - The genome of Red clover necrotic mosaic virus (RCNMV) in the genus Dianthovirus
      is divided into two RNA molecules of RNA1 and RNA2, which have no cap structure
      at the 5' end and no poly(A) tail at the 3' end. The 3' untranslated region (3'
      UTR) of RCNMV RNA1 contains an essential RNA element (3'TE-DR1), which is
      required for cap-independent translation. In this study, we investigated a cap
      independent translational mechanism of RNA2 using a firefly luciferase (Luc) gene
      expression assay system in cowpea protoplasts and a cell-free lysate (BYL)
      prepared from evacuolated tobacco BY2 protoplasts. We were unable to detect cis
      acting RNA sequences in RNA2 that can replace the function of a cap structure,
      such as the 3'TE-DR1 of RNA1. However, the uncapped reporter RNA2, RNA2-Luc, in
      which the Luc open reading frame (ORF) was inserted between the 5' UTR and the
      movement protein ORF, was effectively translated in the presence of p27 and p88
      in protoplasts in which RNA2-Luc was replicated. Time course experiments in
      protoplasts showed that the translational activity of RNA2-Luc did not reflect
      the amount of RNA2. Mutations in cis-acting RNA replication elements of RNA2
      abolished the cap-independent translational activity of RNA2-Luc, suggesting that
      the translational activity of RNA2-Luc is coupled to RNA replication. Our results
      show that the translational mechanism differs between two segmented genomic RNAs
      of RCNMV. We present a model in which only RNA2 that is generated de novo through
      the viral RNA replication machinery functions as mRNA for translation.

PMID- 16571794
TI  - Stable association of herpes simplex virus with target membranes is triggered by
      low pH in the presence of the gD receptor, HVEM.
AB  - Using a liposome-binding assay, we investigated the requirements for activation
      of herpes simplex virus (HSV) into a state capable of membrane interaction.
      Virions were mixed with liposomes along with the ectodomain of one of three gD
      receptors (HVEMt, nectin-1t, or nectin-2t) and incubated under different pH and
      temperature conditions. Virions failed to associate with liposomes in the
      presence of nectin-1 or nectin-2 at any temperature or pH tested. In contrast,
      HVEMt triggered association of HSV with liposomes at pH 5.3 or 5.0 when incubated
      at 37 degrees C, suggesting that HVEM binding and mildly acidic pH at a
      physiological temperature provide coactivation signals, allowing virus
      association with membranes. Virions incubated with HVEMt at 37 degrees C without
      liposomes rapidly lost infectivity upon exposure to pH 5.0, suggesting that these
      conditions lead to irreversible virus inactivation in the absence of target
      membranes. Consistent with the idea that soluble receptor molecules provide a
      trigger for HSV entry, HVEMt promoted virus entry into receptor-deficient CHO K1
      cells. However, in B78H1 cells, HVEMt promoted virus entry with markedly lower
      efficiency. Interestingly, HSV entry into receptor-bearing CHO K1 cells has been
      shown to proceed via a pH-dependent manner, whereas HSV entry into receptor
      bearing B78H1 cells is pH independent. Based on these observations, we propose
      that the changes triggered by HVEM and mildly acidic pH that allow liposome
      association are similar or identical to changes that occur during pH-dependent
      HSV entry.

PMID- 16571796
TI  - Identification of functional domains in herpes simplex virus 2 glycoprotein B.
AB  - Glycoprotein B (gB) is one of four membrane proteins that are essential for the
      entry of herpes simplex viruses (HSV) into cells, and coexpression of the same
      combination of proteins in transfected cells results in cell fusion. The latter
      effect is reminiscent of the ability of virus infection to cause cell fusion,
      particularly since the degree of fusion is greatly increased by syncytial
      mutations in gB. Despite intensive efforts with the gB homologs of HSV and some
      other herpesviruses, information about functionally important regions in the 700
      amino-acid ectodomain of this protein is very limited at present. This is largely
      due to the misfolding of the majority of the mutants examined. It was shown
      previously that the percentage of correctly folded mutants could be increased by
      targeting only predicted loop regions (i.e., not alpha-helix or beta-strand), and
      by using this approach new functional domains in HSV-2 gB have now been
      identified.

PMID- 16571798
TI  - The ribosomal shunt translation strategy of cauliflower mosaic virus has evolved
      from ancient long terminal repeats.
AB  - We have screened portions of the large intergenic region of the Cauliflower
      mosaic virus (CaMV) genome for promoter activity in baker's yeast (Saccharomyces
      cerevisiae) and have identified an element that contributes to promoter activity
      in yeast but has negligible activity in plant cells when expressed in an
      agroinfiltration assay. A search of the yeast genome sequence revealed that the
      CaMV element had sequence similarity with the R region of the long terminal
      repeat (LTR) of the yeast Ty1 retrotransposon, with significant statistical
      confidence. In plants, the same CaMV sequence has been shown to have an essential
      role in the ribosomal shunt mechanism of translation, as it forms the base of the
      right arm of the stem-loop structure that is required for the ribosomal shunt.
      Since the left arm of the stem-loop structure must represent an imperfect reverse
      copy of the right arm, we propose that the ribosomal shunt has evolved from a
      pair of LTRs that have become incorporated end to end into the CaMV genome.

PMID- 16571797
TI  - Full genomic analysis of human rotavirus strain B4106 and lapine rotavirus strain
      30/96 provides evidence for interspecies transmission.
AB  - The Belgian rotavirus strain B4106, isolated from a child with gastroenteritis,
      was previously found to have VP7 (G3), VP4 (P[14]), and NSP4 (A genotype) genes
      closely related to those of lapine rotaviruses, suggesting a possible lapine
      origin or natural reassortment of strain B4106. To investigate the origin of this
      unusual strain, the gene sequences encoding VP1, VP2, VP3, VP6, NSP1, NSP2, NSP3,
      and NSP5/6 were also determined. To allow comparison to a lapine strain, the 11
      double-stranded RNA segments of a European G3P[14] rabbit rotavirus strain 30/96
      were also determined. The complete genome similarity between strains B4106 and
      30/96 was 93.4% at the nucleotide level and 96.9% at the amino acid level. All 11
      genome segments of strain B4106 were closely related to those of lapine
      rotaviruses and clustered with the lapine strains in phylogenetic analyses. In
      addition, sequence analyses of the NSP5 gene of strain B4106 revealed that the
      altered electrophoretic mobility of NSP5, resulting in a super-short pattern, was
      due to a gene rearrangement (head-to-tail partial duplication, combined with two
      short insertions and a deletion). Altogether, these findings confirm that a
      rotavirus strain with an entirely lapine genome complement was able to infect and
      cause severe disease in a human child.

PMID- 16571799
TI  - Intrarectal immunization with rotavirus 2/6 virus-like particles induces an
      antirotavirus immune response localized in the intestinal mucosa and protects
      against rotavirus infection in mice.
AB  - Rotavirus (RV) is the main etiological agent of severe gastroenteritis in
      infants, and vaccination seems the most effective way to control the disease.
      Recombinant rotavirus-like particles composed of the viral protein 6 (VP6) and
      VP2 (2/6-VLPs) have been reported to induce protective immunity in mice when
      administered by the intranasal (i.n.) route. In this study, we show that
      administration of 2/6-VLPs by the intrarectal (i.r.) route together with either
      cholera toxin (CT) or a CpG-containing oligodeoxynucleotide as the adjuvant
      protects adult mice against RV infection. Moreover, when CT is used, RV shedding
      in animals immunized by the i.r. route is even reduced in comparison with that in
      animals immunized by the i.n. route. Humoral and cellular immune responses
      induced by these immunization protocols were analyzed. We found that although
      i.r. immunization with 2/6-VLPs induces lower RV-specific immunoglobulin G (IgG)
      and IgA levels in serum, intestinal anti-RV IgA production is higher in mice
      immunized by the i.r. route. Cellular immune response has been evaluated by
      measuring cytokine production by spleen and Peyer's patch cells (PPs) after ex
      vivo restimulation with RV. Mice immunized by the i.n. and i.r. routes display
      higher gamma interferon production in spleen and PPs, respectively. In
      conclusion, we demonstrate that i.r. immunization with 2/6-VLPs protects against
      RV infection in mice and is more efficient than i.n. immunization in inducing an
      anti-RV immune response in intestinal mucosa.

PMID- 16571800
TI  - Evidence that the human cytomegalovirus IE2-86 protein binds mdm2 and facilitates
      mdm2 degradation.
AB  - Levels of the p53 tumor suppressor protein are increased in human cytomegalovirus
      (HCMV)-infected cells and may be important for HCMV pathogenesis. In normal cells
      p53 levels are kept low due to an autoregulatory feedback loop where p53
      activates the transcription of mdm2 and mdm2 binds and ubiquitinates p53,
      targeting p53 for proteasomal degradation. Here we report that, in contrast to
      uninfected cells, mdm2 was undetectable upon treatment of infected fibroblasts
      with the proteasome inhibitor MG132. Cellular depletion of mdm2 was reproducible
      in p53-null cells transfected with the HCMV IE2-86 protein, but not with IE172,
      independently of the endogenous mdm2 promoter. IE2-86 also prevented the
      emergence of presumably ubiquitinated species of p53. The regions of IE2-86
      important for mdm2 depletion were those containing the sequences corresponding to
      the putative zinc finger and C-terminal acidic motifs. mdm2 and IE2-86
      coimmunoprecipitated in transfected and infected cell lysates and in a cell-free
      system. IE2-86 blocked mdm2's p53-independent transactivation of the cyclin A
      promoter in transient-transfection experiments. Pulse-chase experiments revealed
      that IE2-86 but not IE1-72 or several loss-of-function IE2-86 mutants increased
      the half-life of p53 and reduced the half-life of mdm2. Short interfering RNA
      mediated depletion of IE2-86 restored the ability of HCMV-infected cells to
      accumulate mdm2 in response to proteasome inhibition. Taken together, the data
      suggest that specific interactions between IE2-86 and mdm2 cause proteasome
      independent degradation of mdm2 and that this may be important for the
      accumulation of p53 in HCMV-infected cells.

PMID- 16571801
TI  - Characterization of functional domains of equine infectious anemia virus Rev
      suggests a bipartite RNA-binding domain.
AB  - Equine infectious anemia virus (EIAV) Rev is an essential regulatory protein that
      facilitates expression of viral mRNAs encoding structural proteins and genomic
      RNA and regulates alternative splicing of the bicistronic tat/rev mRNA. EIAV Rev
      is characterized by a high rate of genetic variation in vivo, and changes in Rev
      genotype and phenotype have been shown to coincide with changes in clinical
      disease. To better understand how genetic variation alters Rev phenotype, we
      undertook deletion and mutational analyses to map functional domains and to
      identify specific motifs that are essential for EIAV Rev activity. All functional
      domains are contained within the second exon of EIAV Rev. The overall
      organization of domains within Rev exon 2 includes a nuclear export signal, a
      large central region required for RNA binding, a nonessential region, and a C
      terminal region required for both nuclear localization and RNA binding.
      Subcellular localization of green fluorescent protein-Rev mutants indicated that
      basic residues within the KRRRK motif in the C-terminal region of Rev are
      necessary for targeting of Rev to the nucleus. Two separate regions of Rev were
      necessary for RNA binding: a central region encompassing residues 57 to 130 and a
      C-terminal region spanning residues 144 to 165. Within these regions were two
      distinct, short arginine-rich motifs essential for RNA binding, including an
      RRDRW motif in the central region and the KRRRK motif near the C terminus. These
      findings suggest that EIAV Rev utilizes a bipartite RNA-binding domain.

PMID- 16571802
TI  - Adaptive evolution and antiviral activity of the conserved mammalian cytidine
      deaminase APOBEC3H.
AB  - The APOBEC3 genes encode cytidine deaminases that act as components of an
      intrinsic immune defense that have potent activity against a variety of
      retroelements. This family of genes has undergone a rapid expansion from one or
      two genes in nonprimate mammals to at least seven members in primates. Here we
      describe the evolution and function of an uncharacterized antiviral effector,
      APOBEC3H, which represents the most evolutionarily divergent APOBEC3 gene found
      in primates. We found that APOBEC3H has undergone significant adaptive evolution
      in primates. Consistent with our previous findings implicating adaptively
      evolving APOBEC3 genes as antiviral effectors, APOBEC3H from Old World monkeys
      (OWMs) has efficient antiviral activity against primate lentiviruses, is
      sensitive to inactivation by the simian immunodeficiency virus Vif protein, and
      is capable of hypermutating retroviral genomes. In contrast, human APOBEC3H is
      inherently poorly expressed in primate cells and is ineffective at inhibiting
      retroviral replication. Both OWM and human APOBEC3H proteins can be expressed in
      bacteria, where they display significant DNA mutator activity. Thus, humans have
      retained an APOBEC3H gene that encodes a functional, but poorly expressed,
      cytidine deaminase with no apparent antiviral activity. The consequences of the
      lack of antiviral activity of human APOBEC3H are likely to be relevant to the
      current-day abilities of humans to combat retroviral challenges.

PMID- 16571803
TI  - Inactivating a cellular intrinsic immune defense mediated by Daxx is the
      mechanism through which the human cytomegalovirus pp71 protein stimulates viral
      immediate-early gene expression.
AB  - Human cytomegalovirus (HCMV) masterfully evades adaptive and innate immune
      responses, allowing infection to be maintained and periodically reactivated for
      the life of the host. Here we show that cells also possess an intrinsic immune
      defense against HCMV that is disarmed by the virus. In HCMV-infected cells, the
      promyelocytic leukemia nuclear body (PML-NB) protein Daxx silences viral
      immediate-early gene expression through the action of a histone deacetylase.
      However, this antiviral tactic is efficiently neutralized by the viral pp71
      protein, which is incorporated into virions, delivered to cells upon infection,
      and mediates the proteasomal degradation of Daxx. This work demonstrates the
      mechanism through which pp71 activates viral immediate-early gene expression in
      HCMV-infected cells. Furthermore, it provides insight into how a PML-NB protein
      institutes an intrinsic immune defense against a DNA virus and how HCMV pp71
      inactivates this defense.

PMID- 16571804
TI  - Inhibition of cellular DNA synthesis by the human cytomegalovirus IE86 protein is
      necessary for efficient virus replication.
AB  - Human cytomegalovirus (HCMV) expresses several proteins that manipulate normal
      cellular functions, including cellular transcription, apoptosis, immune response,
      and cell cycle control. The IE2 gene, which is expressed from the HCMV major
      immediate-early (MIE) promoter, encodes the IE86 protein. IE86 is a
      multifunctional protein that is essential for viral replication. The functions of
      IE86 include transactivation of cellular and viral early genes, negative
      autoregulation of the MIE promoter, induction of cell cycle progression from
      G0/G1 to G1/S, and arresting cell cycle progression at the G1/S transition in p53
      positive human foreskin fibroblast (HFF) cells. Mutations were introduced into
      the IE2 gene in the context of the viral genome using bacterial artificial
      chromosomes (BACs). From these HCMV BACs, a recombinant virus (RV) with a single
      amino acid substitution in the IE86 protein was isolated that replicates slower
      and to lower titers than wild-type HCMV. HFF cells infected with the Q548R RV
      undergo cellular DNA synthesis and do not arrest at any point in the cell cycle.
      The Q548R RV is able to negatively autoregulate the MIE promoter, transactivate
      viral early genes, activate cellular E2F-responsive genes, and produce infectious
      virus. This is the first report of a viable recombinant HCMV that is unable to
      inhibit cellular DNA synthesis in infected HFF cells.

PMID- 16571805
TI  - White spot syndrome virus open reading frame 222 encodes a viral E3 ligase and
      mediates degradation of a host tumor suppressor via ubiquitination.
AB  - We have characterized a white spot syndrome virus (WSSV) RING-H2-type protein,
      WSSV222, which is involved in ubiquitination. WSSV222 exhibits RING-H2-dependent
      E3 ligase activity in vitro in the presence of the specific conjugating enzyme
      UbcH6. Mutations in the RING-H2 domain abolished WSSV222-dependent
      ubiquitination, revealing the importance of this domain in WSSV222 function.
      Yeast two-hybrid and pull-down analyses revealed that WSSV222 interacts with a
      shrimp tumor suppressor-like protein (TSL) sharing 60% identity with human OVCA1.
      To better characterize the interaction of WSSV222 and TSL in vivo, we established
      a stable TSL-expressing cell line derived from the human ovarian cancer cell line
      A2780, where we observed a TSL-dependent prolonged G1 phase. Furthermore, we
      detected WSSV222-mediated ubiquitination and MG132-sensitive degradation of TSL
      both in shrimp primary cell culture and in the TSL-expressing cell line.
      Transient expression of TSL in BHK cells leads to apoptosis, which was rescued by
      WSSV222. Taken together, our data suggest that WSSV222 acts as an antiapoptosis
      protein by ubiquitin-mediated proteolysis of TSL to ensure successful WSSV
      replication in shrimp.

PMID- 16571806
TI  - Phosphorylation mutants of JC virus agnoprotein are unable to sustain the viral
      infection cycle.
AB  - Many eukaryotic and viral regulatory proteins are known to undergo
      posttranslational modifications including phosphorylation, which plays a critical
      role in many aspects of cell function. Previous studies from our and other
      laboratories indicated that the JC virus (JCV) late regulatory protein,
      agnoprotein, plays an important role in the JCV life cycle. Agnoprotein contains
      several potential phosphorylation sites, including Ser7, Ser11, and Thr21, which
      are potential targets for the serine/threonine-specific protein kinase C (PKC).
      In this study, we investigated the functional significance of these
      phosphorylation sites for the activity of agnoprotein. In vitro and in vivo
      kinase assays demonstrated that agnoprotein is a target for phosphorylation by
      PKC. In addition, each of the PKC phosphorylation sites was mutated to Ala singly
      and in combination, and the effects of these mutations on the JCV life cycle were
      analyzed. Although the expression of each mutant agnoprotein was detectable
      during the infection cycle, virus containing each of these mutations failed to
      propagate. These results contrast with those obtained with an agnoprotein start
      codon point (Pt) mutant where agnoprotein expression was completely inhibited.
      The Pt mutant was viable but replicates less efficiently than the wild type (WT).
      Moreover, conservative substitutions at PKC phosphorylation sites (Ser7, Ser11,
      and Thr21 to Asp) resulted in a viable virus, which further demonstrate the
      importance of these sites on agnoprotein function. Further analysis of the
      mutants by viral release assay and electron microscopy studies revealed that
      viral particles were efficiently released from infected cells and morphologically
      indistinguishable from those of WT but were deficient in DNA content. This may
      account for the defective propagation of the mutants. These results imply that
      phosphorylated forms of agnoprotein may have essential functions in the viral
      life cycle and serve as potential targets for therapeutic interventions to limit
      JCV propagation and JCV-induced diseases.

PMID- 16571808
TI  - Function of bovine CD46 as a cellular receptor for bovine viral diarrhea virus is
      determined by complement control protein 1.
AB  - The pestivirus bovine viral diarrhea virus (BVDV) was shown to bind to the bovine
      CD46 molecule, which subsequently promotes entry of the virus. To assess the
      receptor usage of BVDV type 1 (BVDV-1) and BVDV-2, 30 BVDV isolates including
      clinical samples were assayed for their sensitivity to anti-CD46 antibodies. With
      a single exception the infectivity of all tested strains of BVDV-1 and BVDV-2 was
      inhibited by anti-CD46 antibodies, which indicates the general usage of CD46 as a
      BVDV receptor. Molecular analysis of the interaction between CD46 and the BVD
      virion was performed by mapping the virus binding site on the CD46 molecule.
      Single complement control protein modules (CCPs) within the bovine CD46 were
      either deleted or replaced by analogous CCPs of porcine CD46, which does not bind
      BVDV. While the epitopes recognized by anti-CD46 monoclonal antibodies which
      block BVDV infection were attributed to CCP1 and CCP2, in functional assays only
      CCP1 turned out to be essential for BVDV binding and infection. Within CCP1 two
      short peptides on antiparallel beta strands were identified as crucial for the
      binding of BVDV. Exchanges of these two peptide sequences were sufficient for a
      loss of function in bovine CD46 as well as a gain of function in porcine CD46.
      Determination of the size constraints of CD46 revealed that a minimum length of
      four CCPs is essential for receptor function. An increase of the distance between
      the virus binding domain and the plasma membrane by insertion of one to six CCPs
      of bovine C4 binding protein exhibited only a minor influence on susceptibility
      to BVDV.

PMID- 16571807
TI  - Characterization of the recombinant adenovirus vector AdYB-1: implications for
      oncolytic vector development.
AB  - Conditionally replicating adenoviruses are a promising new modality for the
      treatment of cancer. However, early clinical trials demonstrate that the efficacy
      of current vectors is limited. Interestingly, DNA replication and production of
      viral particles do not always correlate with virus-mediated cell lysis and virus
      release depending on the vector utilized for infection. However, we have
      previously reported that nuclear accumulation of the human transcription factor
      YB-1 by regulating the adenoviral E2 late promoter facilitates viral DNA
      replication of E1-deleted adenovirus vectors which are widely used for cancer
      gene therapy. Here we report the promotion of virus-mediated cell killing as a
      new function of the human transcription factor YB-1. In contrast to the E1A
      deleted vector dl312 the first-generation adenovirus vector AdYB-1, which
      overexpresses YB-1 under cytomegalovirus promoter control, led to necrosis-like
      cell death, virus production, and viral release after infection of A549 and U2OS
      tumor cell lines. Our data suggest that the integration of YB-1 in oncolytic
      adenoviruses is a promising strategy for developing oncolytic vectors with
      enhanced potency against different malignancies.

PMID- 16571809
TI  - Antibody production and in vitro behavior of CD27-defined B-cell subsets:
      persistent hepatitis C virus infection changes the rules.
AB  - There is growing interest in the tendency of B cells to change their functional
      program in response to overwhelming antigen loading, perhaps by regulating
      specific parameters, such as efficiency of activation, proliferation rate,
      differentiation to antibody-secreting cells (ASC), and rate of cell death in
      culture. We show that individuals persistently infected with hepatitis C virus
      (HCV) carry high levels of circulating immunoglobulin G (IgG) and IgG-secreting
      cells (IgG-ASC). Thus, generalized polyclonal activation of B-cell functions may
      be supposed. While IgGs include virus-related and unrelated antibodies, IgG-ASC
      do not include HCV-specific plasma cells. Despite signs of widespread activation,
      B cells do not accumulate and memory B cells seem to be reduced in the blood of
      HCV-infected individuals. This apparent discrepancy may reflect the
      unconventional activation kinetics and functional responsiveness of the CD27+ B
      cell subset in vitro. Following stimulation with T-cell-derived signals in the
      absence of B-cell receptor (BCR) engagement, CD27+ B cells do not expand but
      rapidly differentiate to secrete Ig and then undergo apoptosis. We propose that
      their enhanced sensitivity to BCR-independent noncognate T-cell help maintains a
      constant level of nonspecific serum antibodies and ASC and serves as a backup
      mechanism of feedback inhibition to prevent exaggerated B-cell responses that
      could be the cause of significant immunopathology.

PMID- 16571810
TI  - Dissecting rotavirus particle-raft interaction with small interfering RNAs:
      insights into rotavirus transit through the secretory pathway.
AB  - Studies of rotavirus morphogenesis, transport, and release have shown that
      although these viruses are released from the apical surface of polarized
      intestinal cells before cellular lysis, they do not follow the classic exocytic
      pathway. Furthermore, increasing evidence suggests that lipid rafts actively
      participate in the exit of rotavirus from the infected cell. In this study, we
      silenced the expression of VP4, VP7, and NSP4 by using small interfering RNAs
      (siRNAs) and evaluated the effect of shutting down the expression of these
      proteins on rotavirus-raft interactions. Silencing of VP4 and NSP4 reduced the
      association of rotavirus particles with rafts; in contrast, inhibition of VP7
      synthesis slightly affected the migration of virions into rafts. We found that
      inhibition of rotavirus migration into lipid rafts, by either siRNAs or
      tunicamycin, also specifically blocked the targeting of VP4 to rafts, suggesting
      that the association of VP4 with rafts is mostly mediated by the formation of
      viral particles in the endoplasmic reticulum (ER). We showed that two populations
      of VP4 exist, one small population that is independently targeted to rafts and a
      second large pool of VP4 whose association with rafts is mediated by particle
      formation in the ER. We also present evidence to support the hypothesis that
      assembly of VP4 into mature virions takes place in the late stages of transit
      through the ER. Finally, we analyzed the progression of rotavirus proteins in the
      exocytic pathway and found that VP4 and virion-assembled VP7 colocalized with
      ERGIC-53, suggesting that rotavirus particles transit through the intermediate
      compartment between the ER and the Golgi complex.

PMID- 16571811
TI  - Rotavirus spike protein VP4 binds to and remodels actin bundles of the epithelial
      brush border into actin bodies.
AB  - We demonstrate here that VP4, a rotaviral protein, is able to specifically bind
      to bundled actin microfilaments that are subsequently profoundly remodeled into
      actin bodies. These cytoplasmic actin bodies do not localize within identified
      intracellular compartments. VP4-induced actin remodeling is similar to
      cytochalasin D effects with kinetics compatible with that of rotavirus infection.
      Actin bundles' remodeling occurs both in infected and in VP4-transfected cells
      and in various cell lines, indicating that this is a general property of the
      viral protein itself. Interestingly, in intestinal epithelial cells, which
      represent the natural target of rotavirus, VP4 is addressed to the apical
      membrane where it binds specifically to brush border actin bundles and elicits
      its remodeling, whereas cytochalasin D impaired all the filamentous actin. These
      observations indicate that these original properties of VP4 likely explain the
      previously described brush border alterations that follow rotavirus infection of
      enterocytes and may also participate to the mechanism of rotavirus final
      assembly.

PMID- 16571812
TI  - The CPSF30 binding site on the NS1A protein of influenza A virus is a potential
      antiviral target.
AB  - The emergence of influenza A viruses resistant to the two existing classes of
      antiviral drugs highlights the need for additional antiviral drugs, particularly
      considering the potential threat of a pandemic of H5N1 influenza A viruses. Here,
      we determine whether influenza A virus replication can be selectively inhibited
      by blocking the ability of its NS1A protein to inhibit the 3'-end processing of
      cellular pre-mRNAs, including beta interferon (IFN-beta) pre-mRNA. Pre-mRNA
      processing is inhibited via the binding of the NS1A protein to the cellular
      CPSF30 protein, and mutational inactivation of this NS1A binding site causes
      severe attenuation of the virus. We demonstrate that binding of CPSF30 is
      mediated by two of its zinc fingers, F2F3, and that the CPSF30/F2F3 binding site
      on the NS1A protein extends from amino acid 144 to amino acid 186. We generated
      MDCK cells that constitutively express epitope-tagged F2F3 in the nucleus,
      although at only approximately one-eighth the level of the NS1A protein produced
      during virus infection. Influenza A virus replication was inhibited in this cell
      line, whereas no inhibition was observed with influenza B virus, whose NS1B
      protein lacks a binding site for CPSF30. Influenza A virus, but not influenza B
      virus, induced increased production of IFN-beta mRNA in the F2F3-expressing
      cells. These results, which indicate that F2F3 inhibits influenza A virus
      replication by blocking the binding of endogenous CPSF30 to the NS1A protein,
      point to this NS1A binding site as a potential target for the development of
      antivirals directed against influenza A virus.

PMID- 16571813
TI  - Analysis of rubella virus capsid protein-mediated enhancement of replicon
      replication and mutant rescue.
AB  - The rubella virus capsid protein (C) has been shown to complement a lethal
      deletion (termed deltaNotI) in P150 replicase protein. To investigate this
      phenomenon, we generated two lines of Vero cells that stably expressed either C
      (C-Vero cells) or C lacking the eight N-terminal residues (Cdelta8-Vero cells), a
      construct previously shown to be unable to complement DeltaNotI. In C-Vero cells
      but not Vero or Cdelta8-Vero cells, replication of a wild-type (wt) replicon
      expressing the green fluorescent protein (GFP) reporter gene (RUBrep/GFP) was
      enhanced, and replication of a replicon with deltaNotI (RUBrep/GFP-deltaNotI) was
      rescued. Surprisingly, replicons with deleterious mutations in the 5' and 3' cis
      acting elements were also rescued in C-Vero cells. Interestingly, the Cdelta8
      construct localized to the nucleus while the C construct localized in the
      cytoplasm, explaining the lack of enhancement and rescue in Cdelta8-Vero cells
      since rubella virus replication occurs in the cytoplasm. Enhancement and rescue
      in C-Vero cells were at a basic step in the replication cycle, resulting in a
      substantial increase in the accumulation of replicon-specific RNAs. There was no
      difference in translation of the nonstructural proteins in C-Vero and Vero cells
      transfected with the wt and mutant replicons, demonstrating that enhancement and
      rescue were not due to an increase in the efficiency of translation of the
      transfected replicon transcripts. In replicon-transfected C-Vero cells, C and the
      P150 replicase protein associated by coimmunoprecipitation, suggesting that C
      might play a role in RNA replication, which could explain the enhancement and
      rescue phenomena. A unifying model that accounts for enhancement of wt replicon
      replication and rescue of diverse mutations by the rubella virus C protein is
      proposed.

PMID- 16571814
TI  - Hepatitis B surface antigen vector delivers protective cytotoxic T-lymphocyte
      responses to disease-relevant foreign epitopes.
AB  - Although hepatitis B surface antigen (HBsAg) per se is highly immunogenic, its
      use as a vector for the delivery of foreign cytotoxic T-lymphocyte (CTL) epitopes
      has met with little success because of constraints on HBsAg stability and
      secretion imposed by the insertion of foreign sequence into critical
      hydrophobic/amphipathic regions. Using a strategy entailing deletion of DNA
      encoding HBsAg-specific CTL epitopes and replacement with DNA encoding foreign
      CTL epitopes, we have derived chimeric HBsAg DNA immunogens which elicited
      effector and memory CTL responses in vitro, and pathogen- and tumor-protective
      responses in vivo, when the chimeric HBsAg DNAs were used to immunize mice. We
      further show that HBsAg DNA recombinant for both respiratory syncytial virus and
      human papillomavirus CTL epitopes elicited simultaneous responses to both
      pathogens. These data demonstrate the efficacy of HBsAg DNA as a vector for the
      delivery of disease-relevant protective CTL responses. They also suggest the
      applicability of the approach of deriving chimeric HBsAg DNA immunogens
      simultaneously encoding protective CTL epitopes for multiple diseases. The DNAs
      we tested formed chimeric HBsAg virus-like particles (VLPs). Thus, our results
      have implications for the development of vaccination strategies using either
      chimeric HBsAg DNA or VLP vaccines. HBsAg is the globally administered vaccine
      for hepatitis B virus infection, inviting its usage as a vector for the delivery
      of immunogens from other diseases.

PMID- 16571815
TI  - In vivo ablation of CD11c-positive dendritic cells increases susceptibility to
      herpes simplex virus type 1 infection and diminishes NK and T-cell responses.
AB  - The precise role of each of the seven individual CD11c+ dendritic cell subsets
      (DCs) identified to date in the response to viral infections is not known. DCs
      serve as critical links between the innate and adaptive immune responses against
      many pathogens, including herpes simplex virus type 1 (HSV-1). The role of DCs as
      mediators of resistance to HSV-1 infection was investigated using CD11c
      diphtheria toxin (DT) receptor-green fluorescent protein transgenic mice, in
      which DCs can be transiently depleted in vivo by treatment with low doses of DT.
      We show that ablation of DCs led to enhanced susceptibility to HSV-1 infection in
      the highly resistant C57BL/6 mouse strain. Specifically, we showed that the
      depletion of DCs led to increased viral spread into the nervous system, resulting
      in an increased rate of morbidity and mortality. Furthermore, we showed that
      ablation of DCs impaired the optimal activation of NK cells and CD4+ and CD8+ T
      cells in response to HSV-1. These data demonstrated that DCs were essential not
      only in the optimal activation of the acquired T-cell response to HSV-1 but also
      that DCs were crucial for innate resistance to HSV-1 infection.

PMID- 16571816
TI  - Influence of N-linked glycosylation of porcine reproductive and respiratory
      syndrome virus GP5 on virus infectivity, antigenicity, and ability to induce
      neutralizing antibodies.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5)
      is the most abundant envelope glycoprotein and a major inducer of neutralizing
      antibodies in vivo. Three putative N-linked glycosylation sites (N34, N44, and
      N51) are located on the GP5 ectodomain, where a major neutralization epitope also
      exists. To determine which of these putative sites are used for glycosylation and
      the role of the glycan moieties in the neutralizing antibody response, we
      generated a panel of GP5 mutants containing amino acid substitutions at these
      sites. Biochemical studies with expressed wild-type (wt) and mutant proteins
      revealed that the mature GP5 contains high-mannose-type sugar moieties at all
      three sites. These mutations were subsequently incorporated into a full-length
      cDNA clone. Our data demonstrate that mutations involving residue N44 did not
      result in infectious progeny production, indicating that N44 is the most critical
      amino acid residue for infectivity. Viruses carrying mutations at N34, N51, and
      N34/51 grew to lower titers than the wt PRRSV. In serum neutralization assays,
      the mutant viruses exhibited enhanced sensitivity to neutralization by wt PRRSV
      specific antibodies. Furthermore, inoculation of pigs with the mutant viruses
      induced significantly higher levels of neutralizing antibodies against the mutant
      as well as the wt PRRSV, suggesting that the loss of glycan residues in the
      ectodomain of GP5 enhances both the sensitivity of these viruses to in vitro
      neutralization and the immunogenicity of the nearby neutralization epitope. These
      results should have great significance for development of PRRSV vaccines of
      enhanced protective efficacy.

PMID- 16571817
TI  - The products of the herpes simplex virus type 1 immediate-early US1/US1.5 genes
      downregulate levels of S-phase-specific cyclins and facilitate virus replication
      in S-phase Vero cells.
AB  - Herpes simplex virus type 1 ICP22-/U(S)1.5- mutants initiate viral gene
      expression in all cells; however, in most cell types, the replication process
      stalls due to an inability to express gamma2 late proteins. Although the function
      of ICP22/U(S)1.5 has not been established, it has been suggested that these
      proteins activate, induce, or repress the activity of cellular proteins during
      infection. In this study, we hypothesized that cell cycle-associated proteins are
      targets of ICP22/U(S)1.5. For this purpose, we first isolated and characterized
      an ICP22-/U(S)1.5- mutant virus, 22/n199. Like other ICP22-/U(S)1.5- mutants,
      22/n199 replicates in a cell-type-specific manner and fails to induce efficient
      gamma2 late gene expression in restrictive cells. Although synchronization of
      restrictive human embryonic lung cells in each phase of the cell cycle did not
      overcome the growth restrictions of 22/n199, synchronization of permissive Vero
      cells in S phase rendered them less able to support 22/n199 plaque formation and
      replication. Consistent with this finding, expression of cellular S-phase cyclins
      was altered in an ICP22/U(S)1.5-dependent manner specifically when S-phase Vero
      cells were infected. Collectively, these observations support the notion that
      ICP22/U(S)1.5 deregulates the cell cycle upon infection of S-phase permissive
      cells by altering expression of key cell cycle regulatory proteins either
      directly or indirectly.

PMID- 16571818
TI  - Envelope conformational changes induced by human immunodeficiency virus type 1
      attachment inhibitors prevent CD4 binding and downstream entry events.
AB  - BMS-488043 is a small-molecule human immunodeficiency virus type 1 (HIV-1) CD4
      attachment inhibitor with demonstrated clinical efficacy. The compound inhibits
      soluble CD4 (sCD4) binding to the 11 distinct HIV envelope gp120 proteins
      surveyed. Binding of BMS-488043 and that of sCD4 to gp120 are mutually exclusive,
      since increased concentrations of one can completely block the binding of the
      other without affecting the maximal gp120 binding capacity. Similarly, BMS-488043
      inhibited virion envelope trimers from binding to sCD4-immunoglobulin G (IgG),
      with decreasing inhibition as the sCD4-IgG concentration increased, and BMS
      488043 blocked the sCD4-induced exposure of the gp41 groove in virions. In both
      virion binding assays, BMS-488043 was active only when added prior to sCD4.
      Collectively, these results indicate that obstruction of gp120-sCD4 interactions
      is the primary inhibition mechanism of this compound and that compound
      interaction with envelope must precede CD4 binding. By three independent
      approaches, BMS-488043 was further shown to induce conformational changes within
      gp120 in both the CD4 and CCR5 binding regions. These changes likely prevent
      gp120-CD4 interactions and downstream entry events. However, BMS-488043 could
      only partially inhibit CD4 binding to an HIV variant containing a specific
      envelope truncation and altered gp120 conformation, despite effectively
      inhibiting the pseudotyped virus infection. Taken together, BMS-488043 inhibits
      viral entry primarily through altering the envelope conformation and preventing
      CD4 binding, and other downstream entry events could also be inhibited as a
      result of these induced conformational changes.

PMID- 16571819
TI  - Novel insights into the pathogenesis of the Graffi murine leukemia retrovirus.
AB  - The Graffi murine leukemia virus (MuLV) was isolated in 1954 by Arnold Graffi,
      who characterized it as a myeloid leukemia-inducing retrovirus. He and his team,
      however, soon observed the intriguing phenomenon of hematological
      diversification, which corresponded to a decrease of myeloid leukemias and an
      increase of other types of leukemias. Recently, we derived two different
      molecular clones corresponding to ecotropic nondefective genomes that were named
      GV-1.2 and GV-1.4. The induced leukemias were classified as myeloid based on
      morphological analysis of blood smears. In this study, we further characterized
      the two variants of the Graffi murine retrovirus, GV-1.2 and GV-1.4, in three
      different strains of mice. We show that the Graffi MuLV is a multipotent
      retrovirus capable of inducing both lymphoid (T- and B-cell) and nonlymphoid
      (myeloid, erythroid, megakaryocytic) leukemia. Many of these are very complex
      with concomitant expression of different hematopoietic lineages. Interestingly, a
      high percentage of megakaryocytic leukemias, a type of leukemia rarely observed
      with MuLVs, arise in the FVB/n strain of mice. The genetic backgrounds of the
      different strains of mice influence greatly the results. Furthermore, the
      enhancer region, different for GV-1.2 and GV-1.4, plays a pivotal role in the
      disease specificity: GV-1.2 induces more lymphoid leukemias, and GV-1.4 induces
      more nonlymphoid ones.

PMID- 16571820
TI  - Herpes simplex virus type 1 and 2 glycoprotein C prevents complement-mediated
      neutralization induced by natural immunoglobulin M antibody.
AB  - Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)
      binds complement component C3b and protects virus from complement-mediated
      neutralization. Differences in complement interacting domains exist between gC of
      HSV-1 (gC1) and HSV-2 (gC2), since the amino terminus of gC1 blocks complement C5
      from binding to C3b, while gC2 fails to interfere with this activity. We
      previously reported that neutralization of HSV-1 gC-null virus by HSV antibody
      negative human serum requires activation of C5 but not of downstream components
      of the classical complement pathway. In this report, we evaluated whether
      activation of C5 is sufficient to neutralize HSV-2 gC-null virus, or whether
      formation of the membrane attack complex by C6 to C9 is required for
      neutralization. We found that activation of the classical complement pathway up
      to C5 was sufficient to neutralize HSV-2 gC-null virus by HSV antibody-negative
      human serum. We evaluated the mechanisms by which complement activation occurred
      in seronegative human serum. Interestingly, natural immunoglobulin M antibodies
      bound to virus, which triggered activation of C1q and the classical complement
      pathway. HSV antibody-negative sera obtained from four individuals differed over
      an approximately 10-fold range in their potency for complement-mediated virus
      neutralization. These findings indicate that humans differ in the ability of
      their innate immune systems to neutralize HSV-1 or HSV-2 gC-null virus and that a
      critical function of gC1 and gC2 is to prevent C5 activation.

PMID- 16571821
TI  - Analysis of equid herpesvirus 1 strain variation reveals a point mutation of the
      DNA polymerase strongly associated with neuropathogenic versus nonneuropathogenic
      disease outbreaks.
AB  - Equid herpesvirus 1 (EHV-1) can cause a wide spectrum of diseases ranging from
      inapparent respiratory infection to the induction of abortion and, in extreme
      cases, neurological disease resulting in paralysis and ultimately death. It has
      been suggested that distinct strains of EHV-1 that differ in pathogenic capacity
      circulate in the field. In order to investigate this hypothesis, it was necessary
      to identify genetic markers that allow subgroups of related strains to be
      identified. We have determined all of the genetic differences between a
      neuropathogenic strain (Ab4) and a nonneuropathogenic strain (V592) of EHV-1 and
      developed PCR/sequencing procedures enabling differentiation of EHV-1 strains
      circulating in the field. The results indicate the occurrence of several major
      genetic subgroups of EHV-1 among isolates recovered from outbreaks over the
      course of 30 years, consistent with the proposal that distinct strains of EHV-1
      circulate in the field. Moreover, there is evidence that certain strain groups
      are geographically restricted, being recovered predominantly from outbreaks
      occurring in either North America or Europe. Significantly, variation of a single
      amino acid of the DNA polymerase is strongly associated with neurological versus
      nonneurological disease outbreaks. Strikingly, this variant amino acid occurs at
      a highly conserved position for herpesvirus DNA polymerases, suggesting an
      important functional role.

PMID- 16571822
TI  - Trim-cyclophilin A fusion proteins can restrict human immunodeficiency virus type
      1 infection at two distinct phases in the viral life cycle.
AB  - The Trim5alpha protein from several primates restricts retroviruses in a capsid
      (CA)-dependent manner. In owl monkeys, the B30.2 domain of Trim5 has been
      replaced by cyclophilin A (CypA) following a retrotransposition. Restriction of
      human immunodeficiency virus type 1 (HIV-1) by the resulting Trim5-CypA fusion
      protein depends on CA binding to CypA, suggesting both that the B30.2 domain
      might be involved in CA binding and that the tripartite RING motif, B-BOX, and
      coiled coil (RBCC) motif domain can function independently of the B30.2 domain in
      restriction. To investigate the potential of RBCCs from other Trims to
      participate in restricting HIV-1, CypA was fused to the RBCC of Trim1, Trim18,
      and Trim19 and tested for restriction. Despite low identity within the RBCC
      domain, all fusion proteins were found to restrict HIV-1 but not the nonbinding
      G89V mutant, indicating that the overall structure of RBCC and not its primary
      sequence was important for the restriction function. The critical interaction
      between CA and Trim-CypA appears to take place soon after viral entry.
      Quantitative PCR analysis of viral reverse transcriptase products revealed that
      the different fusion proteins block HIV-1 at two distinct stages of its life
      cycle, either prior to reverse transcription or just before integration. With
      Trim1 and Trim18, this timing is dependent on the length of the Trim component of
      the fusion protein. These observations suggest that restriction factor binding
      can have different mechanistic consequences.

PMID- 16571824
TI  - Mucosal immunization with surface-displayed severe acute respiratory syndrome
      coronavirus spike protein on Lactobacillus casei induces neutralizing antibodies
      in mice.
AB  - Induction of mucosal immunity may be important for preventing SARS-CoV
      infections. For safe and effective delivery of viral antigens to the mucosal
      immune system, we have developed a novel surface antigen display system for
      lactic acid bacteria using the poly-gamma-glutamic acid synthetase A protein
      (PgsA) of Bacillus subtilis as an anchoring matrix. Recombinant fusion proteins
      comprised of PgsA and the Spike (S) protein segments SA (residues 2 to 114) and
      SB (residues 264 to 596) were stably expressed in Lactobacillus casei. Surface
      localization of the fusion protein was verified by cellular fractionation
      analyses, immunofluorescence microscopy, and flow cytometry. Oral and nasal
      inoculations of recombinant L. casei into mice resulted in high levels of serum
      immunoglobulin G (IgG) and mucosal IgA, as demonstrated by enzyme-linked
      immunosorbent assays using S protein peptides. More importantly, these antibodies
      exhibited potent neutralizing activities against severe acute respiratory
      syndrome (SARS) pseudoviruses. Orally immunized mice mounted a greater
      neutralizing-antibody response than those immunized intranasally. Three new
      neutralizing epitopes were identified on the S protein using a peptide
      neutralization interference assay (residues 291 to 308, 520 to 529, and 564 to
      581). These results indicate that mucosal immunization with recombinant L. casei
      expressing SARS-associated coronavirus S protein on its surface provides an
      effective means for eliciting protective immune response against the virus.

PMID- 16571823
TI  - Dissecting the regions of virion-associated Kaposi's sarcoma-associated
      herpesvirus complement control protein required for complement regulation and
      cell binding.
AB  - Complement, which bridges innate and adaptive immune responses as well as humoral
      and cell-mediated immunity, is antiviral. Kaposi's sarcoma-associated herpesvirus
      (KSHV) encodes a lytic cycle protein called KSHV complement control protein (KCP)
      that inhibits activation of the complement cascade. It does so by regulating C3
      convertases, accelerating their decay, and acting as a cofactor for factor I
      degradation of C4b and C3b, two components of the C3 and C5 convertases. These
      complement regulatory activities require the short consensus repeat (SCR) motifs,
      of which KCP has four (SCRs 1 to 4). We found that in addition to KCP being
      expressed on the surfaces of experimentally infected endothelial cells, it is
      associated with the envelope of purified KSHV virions, potentially protecting
      them from complement-mediated immunity. Furthermore, recombinant KCP binds
      heparin, an analogue of the known KSHV cell attachment receptor heparan sulfate,
      facilitating infection. Treating virus with an anti-KCP monoclonal antibody
      (MAb), BSF8, inhibited KSHV infection of cells by 35%. Epitope mapping of MAb
      BSF8 revealed that it binds within SCR domains 1 and 2, also the region of the
      protein involved in heparin binding. This MAb strongly inhibited classical C3
      convertase decay acceleration by KCP and cofactor activity for C4b cleavage but
      not C3b cleavage. Our data suggest similar topological requirements for cell
      binding by KSHV, heparin binding, and regulation of C4b-containing C3 convertases
      but not for factor I-mediated cleavage of C3b. Importantly, they suggest KCP
      confers at least two functions on the virion: cell binding with concomitant
      infection and immune evasion.

PMID- 16571825
TI  - Recovery of a recombinant salmonid alphavirus fully attenuated and protective for
      rainbow trout.
AB  - Sleeping disease virus (SDV) is a member of the new Salmonid alphavirus genus
      within the Togaviridae family. The single-stranded RNA genome of SDV is 11,894
      nucleotides long, excluding the 3' poly(A) tail. A full-length cDNA has been
      generated; the cDNA was fused to a hammerhead ribozyme sequence at the 5' end and
      inserted into a transcription plasmid (pcDNA3) backbone, yielding pSDV. By
      transfection of pSDV into fish cells, recombinant SDV (rSDV) was successfully
      recovered. Demonstration of the recovery of rSDV was provided by
      immunofluorescence assay on rSDV-infected cells and by the presence of a genetic
      tag, a BlpI restriction enzyme site, introduced into the rSDV RNA genome. SDV
      infectious cDNA was used for two kinds of experiments (i) to evaluate the impact
      of various targeted mutations in nsP2 on viral replication and (ii) to study the
      virulence of rSDV in trout. For the latter aspect, when juvenile trout were
      infected by immersion in a water bath with the wild-type virus-like rSDV, no
      deaths or signs of disease appeared in fish, although they were readily infected.
      In contrast, cumulative mortality reached 80% in fish infected with the wild-type
      SDV (wtSDV). When rSDV-infected fish were challenged with wtSDV 3 and 5 months
      postinfection, a long-lasting protection was demonstrated. Interestingly, a
      variant rSDV (rSDV14) adapted to grow at a higher temperature, 14 degrees C
      instead of 10 degrees C, was shown to become pathogenic for trout. Comparison of
      the nucleotide sequences of wtSDV, rSDV, and rSDV14 genomes evidenced several
      amino acid changes, and some changes may be linked to the pathogenicity of SDV in
      trout.

PMID- 16571826
TI  - Functional analysis of the tick-borne encephalitis virus cyclization elements
      indicates major differences between mosquito-borne and tick-borne flaviviruses.
AB  - The linear, positive-stranded RNA genome of flaviviruses is thought to adopt a
      circularized conformation via interactions of short complementary sequence
      elements located within its terminal regions. This process of RNA cyclization is
      a crucial precondition for RNA replication. In the case of mosquito-borne
      flaviviruses, highly conserved cyclization sequences (CS) have been identified,
      and their functionality has been experimentally confirmed. Here, we provide an
      experimental identification of CS elements of tick-borne encephalitis virus
      (TBEV). These elements, termed 5'-CS-A and 3'-CS-A, are conserved among various
      tick-borne flaviviruses, but they are unrelated to the mosquito-borne CS elements
      and are located at different genomic positions. The 5'-CS-A element is situated
      upstream rather than downstream of the AUG start codon and, in contrast to
      mosquito-borne flaviviruses, it was found that the entire protein C coding region
      is not essential for TBEV replication. The complementary 3'-CS-A element is
      located within the bottom stem rather than upstream of the characteristic 3'
      terminal stem-loop structure, implying that this part of the proposed structure
      cannot be formed when the genome is in its circularized conformation. Finally, we
      demonstrate that the CS-A elements can also mediate their function when the 5'-CS
      A element is moved from its natural position to one corresponding to the mosquito
      borne CS. The recognition of essential RNA elements and their differences between
      mosquito-borne and tick-borne flaviviruses has practical implications for the
      design of replicons in vaccine and vector development.

PMID- 16571827
TI  - Apoptosis of liver-derived cells induced by parvovirus B19 nonstructural protein.
AB  - Parvovirus B19 has been implicated in some cases of acute fulminant non-A, non-B,
      non-C, non-G liver failure. Our laboratory previously demonstrated that B19
      infection of hepatocytes induces apoptosis and that the B19 viral nonstructural
      protein, NS1, may play a critical role. To study the involvement of NS1 in
      apoptosis of liver cells, we generated a fusion protein of NS1 with enhanced
      green fluorescent protein (eGFP) in a system allowing for inducible gene
      expression. Transfection of the liver-derived cell line HepG2 with the eGFP/NS1
      vector allowed expression of the fusion protein, which was visualized by
      fluorescence microscopy and demonstrated by immunoblotting. The fusion protein
      localized to discrete domains in the nucleus. Transfection of HepG2 cells with
      the eGFP/NS1 vector led to apoptosis of 35% of transfected cells, a sevenfold
      increase over cells transfected with the parent eGFP expression vector. Mutation
      of the eGFP/NS1 vector to eliminate the nucleoside triphosphate-binding site of
      NS1 significantly decreased apoptosis, as did treatment of transfected cells with
      inhibitors of caspase 3 or 9. Neutralization of tumor necrosis factor alpha or
      Fas ligand had no effect on apoptosis. These results demonstrate that NS1 is
      sufficient to induce apoptosis in liver-derived cells and that it does so through
      the initiation of an intrinsic caspase pathway.

PMID- 16571828
TI  - Formation of nsP3-specific protein complexes during Sindbis virus replication.
AB  - Alphaviruses are arthropod-borne viruses (arboviruses) that include a number of
      important human and animal pathogens. Their replication proceeds in the cytoplasm
      of infected cells and does not directly depend on nuclei. Alphaviruses encode
      only four nonstructural proteins that are required for the replication of viral
      genome and transcription of the subgenomic RNA. However, the replicative enzyme
      complexes (RCs) appear to include cellular proteins and assemble on cellular
      organelles. We have developed a set of recombinant Sindbis (SIN) viruses with
      green fluorescent protein (GFP) insertions in one of the nonstructural proteins,
      nsP3, to further understand the RCs' genesis and structure. We studied the
      assembly of nsP3/GFP-containing protein complexes at different stages of
      infection and isolated a combination of cellular proteins that are associated
      with SIN nsP3. We demonstrated the following. (i) SIN nsP3 can tolerate the
      insertion of GFP into different fragments of the coding sequence; the designed
      recombinant viruses are viable, and their replication leads to the assembly of
      nsP3/GFP chimeric proteins into gradually developing, higher-order structures
      differently organized at early and late times postinfection. (ii) At late times
      postinfection, nsP3 is assembled into complexes of similar sizes, which appear to
      be bound to cytoskeleton filaments and can aggregate into larger structures.
      (iii) Protein complexes that are associated with nsP3/GFP contain a high
      concentration of cytoskeleton proteins, chaperones, elongation factor 1A,
      heterogeneous nuclear ribonucleoproteins, 14-3-3 proteins, and some of the
      ribosomal proteins. These proteins are proposed to be essential for SIN RC
      formation and/or functioning.

PMID- 16571829
TI  - Baculovirus-mediated gene delivery into Mammalian cells does not alter their
      transcriptional and differentiating potential but is accompanied by early viral
      gene expression.
AB  - Gene delivery to neural cells is central to the development of transplantation
      therapies for neurological diseases. In this study, we used a baculovirus derived
      from the domesticated silk moth, Bombyx mori, as vector for transducing a human
      cell line (HEK293) and primary cultures of rat Schwann cells. Under optimal
      conditions of infection with a recombinant baculovirus containing the reporter
      green fluorescent protein gene under mammalian promoter control, the infected
      cells express the transgene with high efficiency. Toxicity assays and
      transcriptome analyses suggest that baculovirus infection is not cytotoxic and
      does not induce differential transcriptional responses in HEK293 cells. Infected
      Schwann cells retain their characteristic morphological and molecular phenotype
      as determined by immunocytochemistry for the marker proteins S-100, glial
      fibrillary acidic protein, and p75 nerve growth factor receptor. Moreover,
      baculovirus-infected Schwann cells are capable of differentiating in vitro and
      express the P0 myelination marker. However, transcripts for several immediate
      early viral genes also accumulate in readily detectable levels in the transduced
      cells. This transcriptional activity raises concerns regarding the long-term
      safety of baculovirus vectors for gene therapy applications. Potential approaches
      for overcoming the identified problem are discussed.

PMID- 16571830
TI  - Cell cycle perturbations induced by infection with the coronavirus infectious
      bronchitis virus and their effect on virus replication.
AB  - In eukaryotic cells, cell growth and division occur in a stepwise, orderly
      fashion described by a process known as the cell cycle. The relationship between
      positive-strand RNA viruses and the cell cycle and the concomitant effects on
      virus replication are not clearly understood. We have shown that infection of
      asynchronously replicating and synchronized replicating cells with the avian
      coronavirus infectious bronchitis virus (IBV), a positive-strand RNA virus,
      resulted in the accumulation of infected cells in the G2/M phase of the cell
      cycle. Analysis of various cell cycle-regulatory proteins and cellular morphology
      indicated that there was a down-regulation of cyclins D1 and D2 (G1 regulatory
      cyclins) and that a proportion of virus-infected cells underwent aberrant
      cytokinesis, in which the cells underwent nuclear, but not cytoplasmic, division.
      We assessed the impact of the perturbations on the cell cycle for virus-infected
      cells and found that IBV-infected G2/M-phase-synchronized cells exhibited
      increased viral protein production when released from the block when compared to
      cells synchronized in the G0 phase or asynchronously replicating cells. Our data
      suggested that IBV induces a G2/M phase arrest in infected cells to promote
      favorable conditions for viral replication.

PMID- 16571831
TI  - Characterization of a torovirus main proteinase.
AB  - Viruses of the order Nidovirales encode huge replicase polyproteins. These are
      processed primarily by the chymotrypsin-like main proteinases (M(pro)s). So far,
      M(pro)s have been studied only for corona-, arteri-, and roniviruses. Here, we
      report the characterization of the M(pro) of toroviruses, the fourth main
      Nidovirus branch. Comparative sequence analysis of polyprotein 1a of equine
      torovirus (EToV) strain Berne, identified a serine proteinase domain, flanked by
      hydrophobic regions. Heterologous expression of this domain resulted in
      autoprocessing at flanking cleavage sites. N-terminal sequence analysis of
      cleavage products tentatively identified FxxQ downward arrow(S, A) as the
      substrate consensus sequence. EToV M(pro) combines several traits of its closest
      relatives. It has a predicted three-domain structure, with two catalytic beta
      barrel domains and an additional C-terminal domain of unknown function. With
      respect to substrate specificity, the EToV M(pro) resembles its coronavirus
      homologue in its preference for P1-Gln, but its substrate-binding subsite, S1,
      more closely resembles that of arteri- and ronivirus M(pro)s, which prefer P1
      Glu. Surprisingly, in contrast to the M(pro)s of corona- and roniviruses, but
      like that of arterivirus, the torovirus M(pro) uses serine instead of cysteine as
      its principal nucleophile. Under the premise that the M(pro)s of corona- and
      toroviruses are more closely related to each other than to those of arteri- and
      roniviruses, the transition from serine- to cysteine-based proteolytic catalysis
      (or vice versa) must have happened more than once in the course of nidovirus
      evolution. In this respect, it is of interest that a mutant EToV M(pro) with a
      Ser165-->Cys substitution retained partial enzymatic activity.

PMID- 16571832
TI  - Expression of baculovirus late and very late genes depends on LEF-4, a component
      of the viral RNA polymerase whose guanyltransferase function is essential.
AB  - Baculovirus lef-4 encodes one subunit of the viral RNA polymerase. Here, we
      demonstrate the essential nature of LEF-4 by RNA interference and bacmid knockout
      technology. Silencing of LEF-4 in wild-type virus-infected cells suppressed
      expression of structural genes, while early expression was unaffected,
      demonstrating its essential role in late gene expression. After transfection of
      insect cells with lef-4 mutant bacmid, no viral progeny was produced, further
      defining its central role in infection. Cotransfection with wild-type lef-4
      plasmid restored normal replication, but plasmid encoding a guanyltransferase
      deficient version failed to rescue. These results emphasize the importance of the
      mRNA capping function of LEF-4.

PMID- 16571833
TI  - Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein.
AB  - Using chemical inhibitors and small interfering RNA (siRNA), we have confirmed
      roles for cathepsin B (CatB) and cathepsin L (CatL) in Ebola virus glycoprotein
      (GP)-mediated infection. Treatment of Ebola virus GP pseudovirions with CatB and
      CatL converts GP1 from a 130-kDa to a 19-kDa species. Virus with 19-kDa GP1
      displays significantly enhanced infection and is largely resistant to the effects
      of the CatB inhibitor and siRNA, but it still requires a low-pH-dependent
      endosomal/lysosomal function. These and other results support a model in which
      CatB and CatL prime GP by generating a 19-kDa intermediate that can be acted upon
      by an as yet unidentified endosomal/lysosomal enzyme to trigger fusion.

PMID- 16571834
TI  - Genomic sequence of rhesus cytomegalovirus 180.92: insights into the coding
      potential of rhesus cytomegalovirus.
AB  - A pathogenic isolate of rhesus cytomegalovirus (rhCMV 180.92) was cloned,
      sequenced, and annotated. Comparisons with the published rhCMV 68.1 genome
      revealed 8 open reading frames (ORFs) in isolate 180.92 that are absent in 68.1,
      10 ORFs in 68.1 that are absent in 180.92, and 34 additional ORFs that were not
      previously annotated. Most of the differences appear to be due to genetic
      rearrangements in both isolates from a region that is frequently altered in human
      CMV (hCMV) during in vitro passage. These results indicate that the rhCMV ORF
      repertoire is larger than previously recognized. Like hCMV, understanding of the
      complete coding capacity of rhCMV is complicated by genomic instability and may
      require comparisons with additional isolates in vitro and in vivo.

PMID- 16571835
TI  - Maternally derived recombinant human anti-hantavirus monoclonal antibodies are
      transferred to mouse offspring during lactation and neutralize virus in vitro.
AB  - Transgenic mice expressing a recombinant human monoclonal antibody (rHMAb)
      against hantavirus were generated. These mice could be used as models to explore
      the possibilities of producing rHMAbs for therapeutic purposes. The highest
      concentration of the rHMAb in the milk of the transgenic females was 6.6 mg/ml.
      The rHMAb was also detected in the sera of pups fed by the transgenic females.
      Both the rHMAbs in the milk of transgenic mice and those in the sera of suckling
      pups were found to be active against hantaviruses, although the light chain of
      the antibody absorbed by the pups was modified by N-linked glycosylation.

PMID- 16571836
TI  - Hepatitis B virus particle formation in the absence of pregenomic RNA and reverse
      transcriptase.
AB  - Cytoplasmic hepatitis B virus (HBV) capsids are not enveloped and secreted unless
      the packaged RNA pregenome is reverse transcribed. The expression of the capsid
      protein C, together with envelope proteins in the absence of pregenomic RNA,
      produced normal amounts of intracellular capsids, but the secretion of virion
      like particles was greatly reduced. The I97L C protein mutant, allowing immature
      nucleocapsid envelopment in the background of an HBV genome, did not promote the
      envelopment of capsids lacking a pregenome, suggesting that this mutation is not
      sufficient to induce secretion competence independently of the pregenome.

PMID- 16571837
TI  - Cellular factors required for Lassa virus budding.
AB  - It is known that Lassa virus Z protein is sufficient for the release of virus
      like particles (VLPs) and that it has two L domains, PTAP and PPPY, in its C
      terminus. However, little is known about the cellular factor for Lassa virus
      budding. We examined which cellular factors are used in Lassa virus Z budding. We
      demonstrated that Lassa Z protein efficiently produces VLPs and uses cellular
      factors, Vps4A, Vps4B, and Tsg101, in budding, suggesting that Lassa virus
      budding uses the multivesicular body pathway functionally. Our data may provide a
      clue to develop an effective antiviral strategy for Lassa virus.

PMID- 16571838
TI  - Hepatitis C virus protease gene diversity in patients coinfected with human
      immunodeficiency virus.
AB  - The clonal variability of the hepatitis C virus (HCV) protease gene in 24
      individuals with HCV genotypes 1a, 1b, 2b, and 3a who were coinfected with the
      human immunodeficiency virus was evaluated. Within-genotype variability at the
      nucleotide and amino acid levels ranged from 6.5 to 8.6% and 2.2 to 3.8%,
      respectively. After adjustments were made for correlation of intrapatient clonal
      variation, mixed-model analysis indicated that nucleotide and amino acid
      variability among patients with different genotypes did not differ significantly.
      However, within individual patients, clonal variability differed by up to 5.3%
      and 5.8% at the nucleotide and amino acid levels, respectively, and genotype 1a
      had significantly greater nucleotide variability than other genotypes (P = 0.01).
      Significant variability exists within HCV protease gene variants at the patient
      level and could affect the effectiveness of HCV protease inhibitors.

PMID- 16571839
TI  - Murine cytomegalovirus interference with antigen presentation contributes to the
      inability of CD8 T cells to control virus in the salivary gland.
AB  - Compared to other organs, murine cytomegalovirus (MCMV) replication in the
      salivary gland is uniquely resistant to CD8 T-cell control. The contribution of
      viral genes that interfere with antigen presentation (VIPRs) to this resistance
      was assessed using a mutant lacking MCMV's known VIPRs. Salivary gland titers of
      the VIPR-deficient virus were at least 10-fold lower than those of the wild type
      during the persistent phase of infection; the defect was reversed by depleting
      CD8 T cells. Thus, VIPRs contribute to CD8 T cells' inability to control virus in
      the salivary gland.

PMID- 16571840
TI  - Terminating artificial nutrition and hydration in persistent vegetative state
      patients: current and proposed state laws.

PMID- 16571841
TI  - G-2548A polymorphism of the leptin gene is correlated with extreme obesity in
      Taiwanese aborigines.
AB  - We examined the genetic associations of the G-2548A polymorphism in the promoter
      of the leptin (LEP) gene and the Gln223Arg (Q223R) polymorphism of the leptin
      receptor (LEPR) gene with obesity. Two hundred twenty-six obese aboriginal
      subjects (BMI > or = 27 kg/m2) and 182 aboriginal subjects with normal weight
      (BMI < 25 kg/m2) participated in this study. The polymorphisms of LEP G-2548A and
      LEPR Q223R were genotyped by polymerase chain reaction/restriction fragment
      length polymorphism, and their anthropometric characteristics were measured.
      Levels of leptin, triglycerides, and cholesterol were measured after overnight
      fasting. We found that the frequencies of the LEP G/G homozygote (22.6%) with
      Mendelian recessive (chi2 = 7.89, p = 0.005) and codominant (chi2 = 7.93, p =
      0.02) models to be higher in the extremely obese subjects (BMI > or = 35 kg/m2)
      than in normal weight subjects (6.9%) but not in moderately obese subjects (35 >
      BMI > or = 27 kg/m2). There was no difference in genotypic frequency of the LEPR
      Q223R polymorphism between the extreme obese and control groups. We suggest that
      the LEP -2548 G/G homozygote plays a genetic recessive role in the development of
      extreme obesity in Taiwanese aborigines.

PMID- 16571842
TI  - Polymorphisms in FOXO gene family and association analysis with BMI.
AB  - Forkhead transcription factors of the FOXO subfamily are emerging as shared
      components of pathways that regulate a variety of cellular functions. In an
      effort to identify genetic polymorphisms in candidate genes to determine
      associations with BMI, we sequenced all exons of the FOXO genes (FOXO1a, FOXO3a,
      and FOXO4) and examined their associations with BMI in a Korean population (n =
      734). Sixteen polymorphisms were identified in FOXO genes: three in FOXO1a, seven
      in FOXO3a, and six in FOXO4. Associations of FOXO polymorphisms with BMI were
      analyzed using multiple regression, adjusting for age and sex as covariates. One
      promoter single nucleotide polymorphism in the 5' flanking region of FOXO3a
      showed significant association with BMI, e.g., the lowest BMI (23.3 +/- 2.69
      kg/m2) was discovered in individuals who were carrying T/T, intermediate BMI
      (26.6 +/- 3.14 kg/m2) was found in heterozygous individuals (C/T), and the
      highest BMI (27.2 +/- 3.47 kg/m2) occurred in individuals who were homozygous for
      the major allele (C/C; p = 0.01).

PMID- 16571844
TI  - Resistin concentrations in murine adipose tissue and serum measured by a new
      enzyme immunoassay.
AB  - OBJECTIVE: In an attempt to clarify the conflicting data on resistin mRNA
      expression and protein analysis by western blotting in adipose tissue and serum,
      we developed a sensitive enzyme-linked immunosorbent assay (ELISA) for direct
      measurement of mouse resistin. RESEARCH METHODS AND PROCEDURES: We developed
      polyclonal antibodies directed to the N (21 to 40) and C (79 to 91) termini of
      mouse resistin. Then, affinity-purified anti-C-terminal resistin immunoglobin G
      (IgG) was biotinylated. ELISA was based on the sandwiching of antigen between
      antibody IgG coated on polystyrene plates and biotinylated antibody IgG. The
      bound biotinylated antibody was quantified with streptavidin-linked horseradish
      peroxidase. RESULTS: New ELISA can measure a concentration as low as 0.5 ng/mL of
      recombinant mouse resistin and is sensitive and specific enough to measure
      resistin protein in various adipose tissues and in sera. In normal mice,
      decreases in resistin concentrations in both white adipose tissue and serum were
      age dependent during 6 to 24 weeks of development. Resistin concentrations were
      significantly higher in omental adipose tissue in comparison with perirenal and
      abdominal adipose tissues and were 2- to 5-fold higher in females than males
      during the growth period. ob/ob mice had significantly lower resistin
      concentrations than the control mice in both sera and the white adipose tissues,
      particularly in the omental fat. The treatment by testosterone, but not
      progesterone or beta-estradiol, in cultured adipocytes reduces resistin protein
      levels in a dose-dependent manner. DISCUSSION: New sensitive ELISA for mouse
      resistin clarified that the resistin concentrations in normal mice were markedly
      elevated in the omental adipose depots as compared with the perirenal and
      abdominal adipocyte depots and significantly elevated compared with adipose
      tissues in genetically obese mice.

PMID- 16571843
TI  - Peptide YY levels are elevated after gastric bypass surgery.
AB  - OBJECTIVE: Mechanisms that promote effective and sustained weight loss in persons
      who have undergone Roux-en-Y gastric bypass surgery are incompletely understood
      but may be mediated, in part, by changes in appetite. Peptide YY (PYY) is a gut
      derived hormone with anorectic properties. We sought to determine whether gastric
      bypass surgery alters PYY levels or response to glucose. RESEARCH METHODS AND
      PROCEDURES: PYY and ghrelin levels after a 75-gram oral glucose tolerance test
      were measured in 6 morbidly obese patients 1.5 +/- 0.7 (SE) years after gastric
      bypass compared with 5 lean and 12 obese controls. RESULTS: After substantial
      body weight loss (36.8 +/- 3.6%) induced by gastric bypass, the PYY response to
      an oral glucose tolerance test was significantly higher than in controls (p =
      0.01). PYY increased approximately 10-fold after a 75-gram glucose load to a peak
      of 303.0 +/- 37.0 pg/mL at 30 minutes (p = 0.03) and remained significantly
      higher than fasting levels for all subsequent time-points. In contrast, PYY
      levels in obese and lean controls increased to a peak of approximately 2-fold,
      which was only borderline significant. Ghrelin levels decreased in a symmetric
      but opposite fashion to that of PYY. DISCUSSION: Gastric bypass results in a more
      robust PYY response to caloric intake, which, in conjunction with decreased
      ghrelin levels, may contribute to the sustained efficacy of this procedure. The
      findings provide further evidence for a role of gut-derived hormones in mediating
      appetite changes after gastric bypass and support further efforts to determine
      whether PYY(3-36) replacement could represent an effective therapy for obesity.

PMID- 16571845
TI  - Retinal vessel diameters and obesity: a population-based study in older persons.
AB  - OBJECTIVE: Obesity is linked with large vessel atherosclerosis and diabetes. Its
      association with microvascular changes is less clear. We investigated the
      associations among retinal vessel diameters, vessel wall signs, and BMI in an
      older population. RESEARCH METHODS AND PROCEDURES: Retinal photographs were taken
      on 3654 persons aged 49+ years at baseline of the Blue Mountains Eye Study in
      Australia. Arteriolar and venular diameters were measured from digitized retinal
      photographs of the right eyes. BMI was calculated as weight (kilograms)/height
      (meters2). Incident obesity was defined in persons with BMI < or = 30 at baseline
      but > 30 after 5 years. A significant weight gain was defined as an increase in
      BMI of 2+ SDs (4 or more units) over the 5-year period. RESULTS: At baseline,
      mean BMI was 26.1 (+/-4.6) in this population. At 5-year examinations, 177 (10.0%
      of 1773 at risk) developed incident obesity, and 136 (6.4% of 2143 at risk) had
      significant weight gain. After adjusting for age, sex, smoking, triglyceride
      levels, and mean arterial blood pressure, persons with wider retinal venular
      diameters had a higher risk of incident obesity (odds ratio, 1.8; 95% confidence
      interval, 1.0 to 3.1, comparing the highest with lowest venular diameter
      quintiles) and significant weight gain (odds ratio, 1.7; 95% confidence interval,
      0.9 to 3.2). These associations were attenuated with further adjustment for
      baseline BMI. Arteriolar diameter was unrelated with baseline or change in BMI.
      DISCUSSION: Wider retinal venular diameter is associated with risk of obesity,
      independent of hypertension, diabetes, lipids, and cigarette smoking. These data
      may support a role for impaired microvascular function in the course of weight
      gain.

PMID- 16571846
TI  - Consequence of omitting or adding a meal in man on body composition, food intake,
      and metabolism.
AB  - OBJECTIVE: To investigate in man the consequence on body composition and related
      biological and metabolic parameters of omitting or adding a meal. RESEARCH
      METHODS AND PROCEDURES: Twenty-four young normal-weight male subjects were
      recruited, 12 usual four-meal and 12 usual three-meal eaters, differing only in
      the consumption of an afternoon meal. They omitted or added a fourth meal during
      a 28-day habituation period and were asked to report their intake on three 3-day
      occasions. Before and after this habituation period, subjects participated in a
      session with a time-blinded procedure, and blood was collected continuously from
      lunch to the spontaneously requested dinner. Body composition, respiratory
      quotient, and biochemical parameters were measured in the late evening preceding
      each session. RESULTS: Omitting a meal was followed by increases in fat mass (360
      +/- 115 grams, p < 0.05), late evening leptin concentration (20.7 +/- 11.0%, p <
      0.05), and respiratory quotient (3.7 +/- 1.4%, p < 0.05). Increase in the
      percentage of dietary fat during the habituation period (+4.1 +/- 2.0%, p < 0.05)
      was correlated with fat mass (r = 0.66, p < 0.05). Adding a meal had no effect,
      but, in both groups, the change in energy content at this fourth eating occasion
      was correlated with the change in adiposity. DISCUSSION: Our results suggest that
      adiposity may increase when young lean male subjects switch from a four- to a
      three-meal pattern by removing their usual afternoon meal. This effect could be
      partly mediated by a change in the macronutrient composition of the diet.

PMID- 16571847
TI  - Relationship of adiponectin with insulin sensitivity in humans, independent of
      lipid availability.
AB  - OBJECTIVE: To test in humans the hypothesis that part of the association of
      adiponectin with insulin sensitivity is independent of lipid availability.
      RESEARCH METHODS AND PROCEDURES: We studied relationships among plasma
      adiponectin, insulin sensitivity (by hyperinsulinemic-euglycemic clamp), total
      adiposity (by DXA), visceral adiposity (VAT; by magnetic resonance imaging), and
      indices of lipid available to muscle, including circulating and intramyocellular
      lipid (IMCL; by 1H-magnetic resonance spectroscopy). Our cohort included normal
      weight to obese men (n = 36). RESULTS: Plasma adiponectin was directly associated
      with insulin sensitivity and high-density lipoprotein-cholesterol and inversely
      with plasma triglycerides but not IMCL. These findings are consistent with
      adiponectin promoting lipid uptake and subsequent oxidation in muscle and
      inhibiting TG synthesis in the liver. In multiple regression models that also
      included visceral and total fat, free fatty acids, TGs, and IMCL, either alone or
      in combination, adiponectin independently predicted insulin sensitivity,
      consistent with some of its insulin-sensitizing effects being mediated through
      mechanisms other than modulation of lipid metabolism. Because VAT directly
      correlated with total fat and all three indices of local lipid availability, free
      fatty acids, and IMCL, an efficient regression model of insulin sensitivity (R2 =
      0.69, p < 0.0001) contained only VAT (part R2 = 0.12, p < 0.002) and adiponectin
      (part R2 = 0.41, p < 0.0001) as independent variables. DISCUSSION: Given the
      broad range of total adiposity and body fat distribution in our cohort, we
      suggest that insulin sensitivity is robustly associated with adiponectin and VAT.

PMID- 16571848
TI  - Sex difference in the relationship between the hypothalamic-pituitary-adrenal
      axis and sex hormones in obesity.
AB  - OBJECTIVE: This study was carried out to investigate the role of sex in the
      regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its relationship
      with testosterone levels in male and female obesity. RESEARCH METHODS AND
      PROCEDURES: Twenty-two obese men (OB-M) and 29 obese women (OB-W) participated in
      the study. Two groups of normal weight men (NW-M) and women (NW-W), respectively,
      served as controls. In basal conditions, blood concentrations of major androgens,
      sex hormone-binding protein, and gonadotropins were assessed, and the free
      androgen index (testosterone x100/sex hormone-binding globulin) was calculated.
      All subjects underwent a combined corticotropin-releasing hormone plus arginine
      vasopressin stimulation test. RESULTS: OB-M and NW-M had higher basal adrenal
      cortical tropic hormone (ACTH) and cortisol levels than their female
      counterparts. In addition, ACTH, but not cortisol basal, levels were
      significantly higher in obese than in normal weight controls in both sexes. OB-W
      had a higher response than OB-M to the combined corticotropin-releasing hormone
      plus arginine-vasopressin test of both ACTH and cortisol [expressed as
      incremental percentage of area under the curve (AUC%)]. The same finding was
      present between NW-W and NW-M. Basal luteinizing hormone levels were negatively
      correlated to ACTH(AUC%) in both OB-W and OB-M. In the OB-W, however, a positive
      correlation was found between cortisol(AUC%) and testosterone (r = 0.48; p =
      0.002), whereas a tendency toward a negative correlation was present in OB-M.
      DISCUSSION: In conclusion, we have shown a significant positive relationship
      between the activity of the HPA axis and testosterone in obese women, which
      suggests a partial responsibility of increased HPA axis activity in determining
      testosterone levels. In addition, it clearly seems that, as reported in normal
      weight subjects, a sex difference in the HPA axis activity still persists even in
      the presence of obesity.

PMID- 16571849
TI  - Relationships among body composition measures in community-dwelling older women.
AB  - OBJECTIVE: To examine whether simple anthropometric measures provide a good
      estimate of total and visceral fat in 146 community-dwelling, older white women
      (mean age, 74.0 +/- 4.1 years). RESEARCH METHODS AND PROCEDURES: Total body fat
      and visceral fat were measured using electron beam computed tomography (EBT).
      Anthropometric parameters (height, weight, BMI, sagittal diameter, and waist
      circumference) were measured using standard techniques. Total percentage body fat
      was assessed using DXA. Spearman correlations were used to examine the
      association between the measures. Linear regression, controlling for age, was
      used to examine the associations between the anthropometric parameters and total
      and visceral body fat measured by EBT. RESULTS: Correlations among body
      composition measures ranged from rho = 0.46 to 0.93 (p < 0.0001). EBT total fat
      was strongly correlated with both DXA estimates of total percentage fat (rho =
      0.86) and BMI (rho = 0.89). Separate linear regression models indicated that BMI,
      waist circumference, sagittal diameter, and DXA total percentage fat were each
      independently related to EBT total fat. BMI had the strongest linear
      relationship, explaining 80% of the model variance (p < 0.0001). Linear
      regression indicated that BMI, waist circumference, and sagittal diameter were
      each independently related to EBT visceral fat, with BMI and sagittal diameter
      explaining approximately 53% of the model variance (p < 0.0001). DISCUSSION: The
      use of simple anthropometric measures such as BMI, sagittal diameter, and waist
      circumference may be an appropriate alternative for more expensive techniques
      when assessing total fat but should be used with caution when estimating visceral
      body fat.

PMID- 16571850
TI  - Validity of hand-to-foot measurement of bioimpedance: standing compared with
      lying position.
AB  - OBJECTIVE: To assess the reliability of the standing measurement of hand-to-foot
      bioimpedance compared with measurements made in the lying position. RESEARCH
      METHODS AND PROCEDURES: In 205 volunteers 6 to 89 years of age, 111 males and 94
      females from six ethnic groups, effects of posture, time, and age on hand-to-foot
      resistance were studied over a range of body size. The effect of time in a
      position on resistance was also recorded in a small subset (n = 10), and repeat
      measurements over 3 days at the same time of the day were recorded in another
      subset (n = 12). RESULTS: Lying impedance was consistently higher than standing,
      with the relationship (resistance lying/resistance standing) for the children (5
      to 14 years) being 1.031, progressing to a ratio of 1.016 in those > 60 years.
      The time spent static in either position did change resistance measurements-a
      decrease of up to 9 Omega (mean 5 Omega, 1.0%) over 10 minutes of standing and an
      increase of up to 7 Omega (mean 3 Omega, 0.7%) with lying. DISCUSSION: In the
      field, measurements of hand-to-foot bioimpedance can be made in the standing
      position, and, with appropriate adjustment, previously validated recumbent
      equations can be used. Given that errors in the measurement of height and weight
      also affect the reliability of the derivation of body fat from bioelectrical
      conductance, the errors that may arise from a more practical standing measurement
      rather than lying are minimal.

PMID- 16571851
TI  - Fat and energy partitioning: longitudinal observations in leptin-treated adults
      homozygous for a Lep mutation.
AB  - OBJECTIVE: Partitioning of body energy content in the aleptinemic ob/ob mouse
      differs from that in wild-type mice, but it is not known whether parallel
      differences exist between humans with leptin (Lep) gene mutations and healthy
      adults. The objective of this study was to evaluate body composition in three
      leptin-treated Turkish adults homozygous for a missense mutation (C-->T
      substitution at codon 105 resulting in Arg-->Trp) of Lep. RESEARCH METHODS AND
      PROCEDURES: Subjects, one male and two female Turkish family members, were
      evaluated at baseline and treated for 18 months with r-MetHuLeptin. Patient data
      (fat mass, energy content) were compared with adult sex-specific predicted values
      (adjusted for weight, height, and age) derived in healthy control subjects.
      RESULTS: Weight loss with leptin treatment was substantial, ranging from 43.9% to
      52.1%. At baseline and with leptin treatment, the two women had a fat mass and
      energy content similar (+/-12%) to predicted values. Baseline fat and energy
      content in the male patient was high compared with predicted values (e.g., fat
      +33%) but approached and reached normal values (e.g., fat, +2%) after 18 months
      of leptin therapy. DISCUSSION: Adult women with Lep mutations had body
      composition similar to normal women at baseline and with leptin treatment. In
      contrast, the man with a Lep mutation had high body fat in the untreated state
      but a normal male phenotype with leptin administration, possibly secondary to
      androgenic fat partitioning effects. Fat and energy partitioning can, thus, be
      quantitatively assessed and linked with potential hormonal mechanisms in humans
      with inherited disturbances in energy regulation.

PMID- 16571852
TI  - Web-based weight management programs in an integrated health care setting: a
      randomized, controlled trial.
AB  - OBJECTIVE: To assess the efficacy of a Web-based tailored behavioral weight
      management program compared with Web-based information-only weight management
      materials. RESEARCH METHODS AND PROCEDURES: Participants, 2862 eligible
      overweight and obese (BMI = 27 to 40 kg/m2) members from four regions of Kaiser
      Permanente's integrated health care delivery system, were randomized to receive
      either a tailored expert system or information-only Web-based weight management
      materials. Weight change and program satisfaction were assessed by self-report
      through an Internet-based survey at 3- and 6-month follow-up periods. RESULTS:
      Significantly greater weight loss at follow-up was found among participants
      assigned to the tailored expert system than among those assigned to the
      information-only condition. Subjects in the tailored expert system lost a mean of
      3 +/- 0.3% of their baseline weight, whereas subjects in the information-only
      condition lost a mean of 1.2 +/- 0.4% (p < 0.0004). Participants were also more
      likely to report that the tailored expert system was personally relevant,
      helpful, and easy to understand. Notably, 36% of enrollees were African-American,
      with enrollment rates higher than the general proportion of African Americans in
      any of the study regions. DISCUSSION: The results of this large, randomized
      control trial show the potential benefit of the Web-based tailored expert system
      for weight management compared with a Web-based information-only weight
      management program.

PMID- 16571853
TI  - Increased exercise capacity after surgically induced weight loss in morbid
      obesity.
AB  - OBJECTIVE: To investigate the effects of surgically induced weight loss on
      exercise capacity in patients with morbid obesity (MO). RESEARCH METHODS AND
      PROCEDURES: A prospective 1-year follow-up study was carried out, with patients
      being their own controls. A symptom-limited cardiopulmonary exercise stress test
      was performed in 31 MO patients (BMI > 40 kg/m2) before and 1 year after
      undergoing bariatric surgery. RESULTS: At 1 year after surgery, weight was
      reduced from 146 +/- 33 to 95 +/- 19 kg (p < 0.001), and BMI went from 51 +/- 4
      to 33 +/- 6 kg/m2 (p < 0.001). After weight loss, obese patients performed each
      workload with lower oxygen consumption, heart rate, systolic arterial pressure,
      and ventilatory volume (p < 0.001). This reduced energy expenditure allowed them
      to increase the duration of their effort test from 13.8 +/- 3.8 to 21 +/- 4.2
      minutes (p < 0.001). Upon finishing the exercise, MO patients before surgery were
      able to reach only 83% of their age-predicted maximal heart rate, and their
      respiratory exchange ratio was 0.87 +/- 0.06. After weight loss, those values
      were 90% and 1 +/- 0.08, respectively (p < 0.01). When we compared the peak O2
      pulse corrected by fat free mass before and after surgery, no significant
      differences between the groups were found. DISCUSSION: After surgically induced
      weight loss, MO patients markedly improved their exercise capacity. This is due
      to the fact that they were able to perform the external work with lower energy
      expenditure and also to increase cardiovascular stress, optimizing the use of
      cardiac reserve. There were no differences in cardiac function before and after
      surgery.

PMID- 16571854
TI  - Effect of a community-based weight management program on weight loss and
      cardiovascular disease risk factors.
AB  - OBJECTIVE: The purpose of our retrospective database analysis was to describe and
      evaluate the outcomes of a weight loss intervention in a community medical
      wellness center. RESEARCH METHODS AND PROCEDURES: Four hundred eighteen
      overweight and obese adults entered the program between 2001 and 2004. Forty
      seven percent completed the 6-month program designed using standards and
      recommendations established by the NIH, the American Dietetic Association, and
      the American Academy of Sports Medicine. Data analysis was limited to 198
      participants (142 women, 56 men) completing the program. RESULTS: Individuals
      completing the 6-month program averaged a weight loss of 7.3% in men and 4.7% in
      women. Fasting lipids and blood glucose improved in both genders regardless of
      age. Outcomes including BMI and lipids improved in women regardless of menopausal
      status or hormone replacement therapy. There was a significant correlation
      between percentage weight loss and number of weekly counseling sessions attended
      and number of visits to the wellness center for exercise. DISCUSSION:
      Participants who complete a structured community-based weight management program
      can achieve significant weight loss and improvement in cardiovascular risk
      factors regardless of age, gender, or menopausal status. Our analysis suggests
      that national treatment guidelines/recommendations for weight management can be
      effectively implemented in a community medical wellness center. The relatively
      high drop-out rate associated with this program suggests the need to identify
      strategies and techniques to enhance adherence and completion of programs.

PMID- 16571855
TI  - Age-dependent changes in body size of Greek boys from 1982 to 2002.
AB  - OBJECTIVE: The prevalence of childhood obesity has been rising during the past
      decades in many parts of the world, including Greece. The dispersion of these
      trends across age, however, is less clear. The aim of this study was to examine
      the relationship between age and 20-year changes in anthropometric
      characteristics of Greek boys. RESEARCH METHODS AND PROCEDURES: A total of 204
      and 106 boys 9 years old, 163 and 274 boys 12 years old, and 161 and 240 boys 15
      years old were randomly recruited in 1982 and 2002, respectively, throughout the
      county of Iraklio, Crete, Greece. Height, weight, and BMI were measured. RESULTS:
      Contemporary 9 and 12 year olds were taller than their peers in 1982 (+2.9% and
      +1.2%, respectively; p < 0.005), but this was not the case for 15 year olds (
      0.8%; p = 0.083). Body weight and BMI were higher now than in the 1980s, and this
      held true for all age groups (p < 0.001). Increases in weight also showed a
      decline with advancing age (+17.4%, +13.9%, and +4.0% for 9, 12, and 15 year
      olds, respectively), whereas BMI changes were similar for those 9 and 12 years of
      age (approximately 10.5%), but were almost 2-fold higher than in 15 year olds
      (+5.5%). DISCUSSION: Contemporary boys are taller, heavier, and have higher BMI
      values than their peers in 1982, but the magnitude of these increases gradually
      declines with advancing age. Rates of increase in BMI, however, seem to have
      greatly accelerated compared with previous decades.

PMID- 16571856
TI  - Dietary linolenic acid and fasting glucose and insulin: the National Heart, Lung,
      and Blood Institute Family Heart Study.
AB  - OBJECTIVE: To assess whether dietary linolenic acid is associated with fasting
      insulin and glucose. RESEARCH METHODS AND PROCEDURES: In a cross-sectional
      design, we studied 3993 non-diabetic participants of the National Heart, Lung,
      and Blood Institute Family Heart Study 25 to 93 years of age. Linolenic acid was
      assessed through a food frequency questionnaire, and laboratory data were
      obtained after at least a 12-hour fast. We used generalized linear models to
      calculate adjusted means of insulin and glucose across quartiles of dietary
      linolenic acid. RESULTS: From the lowest to the highest sex-specific quartile of
      dietary linolenic acid, means +/- standard error for logarithmic transformed
      fasting insulin were 4.06 +/- 0.02 (reference), 4.09 +/- 0.02, 4.13 +/- 0.02, and
      4.17 +/- 0.02 pM, respectively (trend, p < 0.0001), after adjustment for age,
      sex, energy intake, waist-to-hip ratio, smoking, and high-density lipoprotein
      cholesterol. When dietary linolenic acid was used as a continuous variable, the
      multivariable adjusted regression coefficient was 0.42 +/- 0.08. There was no
      association between dietary linolenic acid and fasting glucose (trend p = 0.82).
      DISCUSSION: Our data suggest that higher consumption of dietary linolenic acid is
      associated with higher plasma insulin, but not glucose levels, in non-diabetic
      subjects. Additional studies are needed to assess whether higher intake of
      linolenic acid results in an increased insulin secretion and improved glucose use
      in vivo.

PMID- 16571857
TI  - Racial and ethnic differences in secular trends for childhood BMI, weight, and
      height.
AB  - OBJECTIVES: The prevalence of childhood overweight in the United States has
      markedly increased over the last 30 years. We examined differences in the secular
      trends for BMI, weight, and height among white, black, and Mexican-American
      children. RESEARCH METHODS AND PROCEDURES: Analyses were based on nationally
      representative data collected from 2 to 17 year olds in four examinations (1971
      1974 through 1999-2002). RESULTS: Overall, black children experienced much larger
      secular increases in BMI, weight, and height than did white children. For
      example, over the 30-year period, the prevalence of overweight increased
      approximately 3-fold (4% to 13%) among 6- to 11-year-old white children but 5
      fold (4% to 20%) among black children. In most sex-age groups, Mexican-American
      children experienced increases in BMI and overweight that were between those
      experienced by blacks and whites. Race/ethnicity differences were less marked
      among 2 to 5 year olds, and in this age group, white children experienced the
      largest increase in overweight (from 4% to 9%). In 1999-2002, the prevalence of
      extreme BMI levels (> or =99th percentile) reached 6% to 7% among black girls and
      Mexican-American boys. DISCUSSION: Because of the strong tracking of childhood
      BMI levels into adulthood, it is likely that the secular increases in childhood
      overweight will greatly increase the burden of adult disease. The further
      development of obesity interventions in different racial/ethnic groups should be
      emphasized.

PMID- 16571858
TI  - Serum amyloid A: a marker of adiposity-induced low-grade inflammation but not of
      metabolic status.
AB  - OBJECTIVE: Adipocytes secrete a series of acute phase proteins including serum
      amyloid A (SAA); the link with metabolic status is unknown. We studied the
      variations of expression of the SAA gene in adipose and liver tissues and of SAA
      serum levels, as well as their relationships with metabolic features during
      weight loss. RESEARCH METHODS AND PROCEDURES: Plasmatic variations of SAA,
      inflammatory markers (high sensitivity C-reactive protein, interleukin-6,
      fibrinogen, and orosomucoid), and adipokines (adiponectin, leptin) were studied
      in 60 morbidly obese patients before and after gastric surgery. For 10 subjects,
      SAA mRNA expression was measured at baseline in subcutaneous white adipose tissue
      (scWAT) and visceral white adipose tissue (vWAT) and in the liver. The evolution
      of SAA mRNA expression was also studied after surgery in scWAT. RESULTS: SAA
      serum concentration displayed a significant reduction 3 months after surgery and
      remained stable beyond 6 months. mRNA expression of inducible SAA isoforms (SAA 1
      and 2) in scWAT was higher than in vWAT (p = 0.01) and the liver (p < 0.01) and
      correlated significantly with BMI, SAA, and high sensitivity C-reactive protein
      serum concentrations but not with metabolic markers (glucose, insulin, lipid
      parameters, adiponectin). SAA serum level and its variation during weight loss
      significantly correlated with adiposity markers (BMI and adipocyte volume, p <
      0.01) and inflammatory markers but not with variations of metabolic parameters.
      The variations of SAA expression in scWAT after surgery correlated with changes
      in BMI and SAA protein serum levels (p < 0.05). DISCUSSION: SAA can be considered
      as a marker of adiposity-induced low-grade inflammation but not of the metabolic
      status of obese subjects.

PMID- 16571859
TI  - Adiponectin, visceral fat, oxidative stress, and early macrovascular disease: the
      Coronary Artery Risk Development in Young Adults Study.
AB  - OBJECTIVE: Adiponectin is a collagen-like product of visceral fat that offers
      apparent protection against macrovascular disease. We evaluated the relationships
      of concentrations of adiponectin with oxidative stress and the major risk factors
      for and/or the presence of macrovascular disease. RESEARCH METHODS AND
      PROCEDURES: Adiponectin was measured by radioimmunoassay in serum from 3045
      fasting participants (ages 33 to 45) of the Coronary Artery Risk Development in
      Young Adults Study. Cross-sectional correlation of the concentrations of
      adiponectin with F2-isoprostane concentrations (a marker of systemic oxidative
      damage), coronary artery calcification (CAC; an estimate of early macrovascular
      disease), and several macrovascular risk factors was analyzed. RESULTS: F2
      isoprostanes and CAC were unrelated to adiponectin after minimal adjustment for
      gender, race, and center. After additional adjustment for insulin resistance and
      waist circumference and other macrovascular risk factors, adiponectin correlated
      positively with high-density lipoprotein-cholesterol (p < 0.0001), F2
      isoprostanes (p < 0.0001), and CAC (less strongly, p < 0.01) and negatively with
      triglycerides (p < 0.0001) and C-reactive protein (marking inflammation, p =
      0.01). DISCUSSION: Although these data are consistent with reduced cardiovascular
      disease risk imparted by adiponectin, the higher circulating levels of
      adiponectin present with oxidative stress and CAC (adjusting for waist and
      insulin resistance) may indicate an enhanced adiponectin secretory response of
      adipose tissue to the metabolic environment present in the early development of
      macrovascular disease. Thus, the elevated levels of adiponectin may comprise an
      attempt to alleviate risk for additional development and progression of
      macrovascular disease in an at-risk environment.

PMID- 16571860
TI  - Associations among education, cortisol rhythm, and BMI in blue-collar women.
AB  - OBJECTIVE: This study sought to test whether a biological measure of chronic
      stress, Delta cortisol, was related to BMI and whether the relationship between
      Delta cortisol and BMI varied according to education and positive affect.
      RESEARCH METHODS AND PROCEDURES: One hundred fifty-four women from a blue-collar
      women's health project in 11 industrial sites in rural North Carolina provided
      saliva for cortisol assays for a substudy on "stress." Delta Cortisol, the
      difference between awakening and midday cortisol measures representing diurnal
      decline, was calculated (lower values = greater stress). BMI was regressed on
      Delta cortisol, education, and positive affect. Analyses were controlled for age,
      race, and worksite. Standardized beta-coefficients were calculated. RESULTS: For
      participants with complete data (n = 129), BMI was greater (beta; 95% confidence
      interval) for women with less than high school education (0.56; 0.18, 0.94) and
      those who completed high school (0.26; -0.05, 0.57) relative to women with
      greater than a high school education (p = 0.009). Delta Cortisol was inversely
      related to BMI (-0.32; -0.59, -0.05; p = 0.022). Education positively modified
      the inverse relationship between Delta cortisol and BMI (p = 0.047). Positive
      affect was negatively associated with BMI (-0.44; -0.82, -0.06; p = 0.026) and
      positively modified the inverse association between Delta cortisol and BMI (0.33;
      -0.03, 0.69; p = 0.074). DISCUSSION: Education and Delta cortisol were inversely
      related to BMI, and the magnitude of the association between Delta cortisol and
      BMI was buffered by higher education. Positive affect was inversely related to
      BMI. Chronic stress is associated with higher BMI, with this relation attenuated
      by higher education and, possibly, a positive affect.

PMID- 16571861
TI  - Visceral fat is an independent predictor of all-cause mortality in men.
AB  - OBJECTIVE: To examine the independent associations of abdominal fat (visceral and
      subcutaneous) and liver fat with all-cause mortality. RESEARCH METHODS AND
      PROCEDURES: Participants included 291 men [97 decedents and 194 controls; mean
      age, 56.4 +/- 12.0 (SD) years] who received a computed tomography (CT)
      examination at the preventive medicine clinic in Dallas, TX, between 1995 and
      1999, with a mean mortality follow-up of 2.2 +/- 1.3 years. Abdominal fat was
      determined using contiguous CT images from the L3-L4 to L4-L5 intervertebral
      space. Liver fat was assessed using the CT-determined liver attenuation value,
      which is inversely related to liver fat. Logistic regression was used to
      determine the independent association between the fat depots and all-cause
      mortality. RESULTS: During the study, there were 97 deaths. Visceral fat [odds
      ratio (OR) per SD: 1.83; 95% CI: 1.23 to 2.73], abdominal subcutaneous fat (1.44;
      1.02 to 2.03), liver fat (0.64; 0.46 to 0.87), and waist circumference (1.41;
      1.01 to 1.98) were significant individual predictors of mortality after
      controlling for age and length of follow-up. In a model including all three fat
      measures (subcutaneous, visceral, and liver fat), age, and length of follow-up,
      only visceral fat (1.93; 1.15 to 3.23) was a significant predictor of mortality.
      DISCUSSION: Visceral fat is a strong, independent predictor of all-cause
      mortality in men.

PMID- 16571862
TI  - Transcriptional repression of Na-K-2Cl cotransporter NKCC1 by hypoxia-inducible
      factor-1.
AB  - Tissue edema is commonly associated with hypoxia. Generally, such episodes of
      fluid accumulation are self-limiting. At present, little is known about
      mechanisms to compensate excessive fluid transport. Here we describe an adaptive
      mechanism to dampen fluid loss during hypoxia. Initial studies confirmed previous
      observations of attenuated electrogenic Cl- secretion after epithelial hypoxia. A
      screen of known ion transporters in Cl- -secreting epithelia revealed selective
      downregulation of Na-K-2Cl cotransporter NKCC1 mRNA, protein, and function.
      Subsequent studies identified transcriptional repression of NKCC1 mediated by
      hypoxia-inducible factor (HIF). Chromatin immunoprecipitation analysis identified
      a functional HIF binding site oriented on the antisense strand of genomic DNA
      downstream of the transcription start site corresponding to the NKCC1 5'
      untranslated region. Additional in vivo studies using conditional Hif1a-null mice
      revealed that the loss of HIF-1alpha in Cl- -secreting epithelia results in a
      loss of NKCC1 repression. These studies describe a novel regulatory pathway for
      NKCC1 transcriptional repression by hypoxia. These results suggest that HIF
      dependent repression of epithelial NKCC1 may provide a compensatory mechanism to
      prevent excessive fluid loss during hypoxia.

PMID- 16571863
TI  - VIP and PACAP regulate localized Ca2+ transients via cAMP-dependent mechanism.
AB  - Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase
      activating polypeptide (PACAP) have been suggested as participants in enteric
      inhibitory neural regulation of gastrointestinal motility. These peptides cause a
      variety of postjunctional responses including membrane hyperpolarization and
      inhibition of contraction. Neuropeptides released from enteric motor neurons can
      elicit responses by direct stimulation of smooth muscle cells as opposed to other
      transmitters that rely on synapses between motor nerve terminals and interstitial
      cells of Cajal. Therefore, we studied the responses of murine colonic smooth
      muscle cells to VIP and PACAP(1-38) with confocal microscopy and patch-clamp
      technique. Localized Ca2+ transients (Ca2+ puffs) were observed in colonic
      myocytes, and these events coupled to spontaneous transient outward currents
      (STOCs). VIP and PACAP increased Ca2+ transients and STOC frequency and
      amplitude. Application of dibutyryl cAMP had similar effects. The adenylyl
      cyclase blocker MDL-12,330A alone did not affect spontaneous Ca2+ puffs and STOCs
      but prevented responses to VIP. Disruption of A-kinase-anchoring protein (AKAP)
      associations by application of AKAP St-Ht31 inhibitory peptide had effects
      similar to those of MDL-12,330A. Inhibition of ryanodine receptor channels did
      not block spontaneous Ca2+ puffs and STOCs but prevented the effects of dibutyryl
      cAMP. These findings suggest that regulation of Ca2+ transients (which couple to
      activation of STOCs) may contribute to the inhibitory effects of VIP and PACAP.
      Regulation of Ca2+ transients by VIP and PACAP occurs via adenylyl cyclase,
      increased synthesis of cAMP, and PKA-dependent regulation of ryanodine receptor
      channels.

PMID- 16571865
TI  - Pollutant particles enhanced H2O2 production from NAD(P)H oxidase and
      mitochondria in human pulmonary artery endothelial cells.
AB  - Particulate matter (PM) induces oxidative stress and cardiovascular adverse
      health effects, but the mechanistic link between the two is unclear. We
      hypothesized that PM enhanced oxidative stress in vascular endothelial cells and
      investigated the enzymatic sources of reactive oxygen species and their effects
      on mitogen-activated protein kinase (MAPK) activation and vasoconstriction. We
      measured the production of extracellular H2O2, activation of extracellular signal
      regulated kinases1/2 (ERK1/2) and p38 MAPKs in human pulmonary artery endothelial
      cells (HPAEC) treated with urban particles (UP; SRM1648), and assessed the
      effects of H2O2 on vasoconstriction in pulmonary artery ring and isolated
      perfused lung. Within minutes after UP treatment, HPAEC increased H2O2 production
      that could be inhibited by diphenyleneiodonium (DPI), apocynin (APO), and sodium
      azide (NaN3). The water-soluble fraction of UP as well as its two transition
      metal components, Cu and V, also stimulated H2O2 production. NaN3 inhibited H2O2
      production stimulated by Cu and V, whereas DPI and APO inhibited only Cu
      stimulated H2O2 production. Inhibitors of other H2O2-producing enzymes, including
      Nomega-methyl-L-argnine, indomethacin, allopurinol, cimetidine, rotenone, and
      antimycin, had no effects. DPI but not NaN3 attenuated UP-induced pulmonary
      vasoconstriction and phosphorylation of ERK1/2 and p38 MAPKs. Knockdown of
      p47phox gene expression by small interfering RNA attenuated UP-induced H2O2
      production and phosphorylation of ERK1/2 and p38 MAPKs. Intravascular
      administration of H2O2 generated by glucose oxidase increased pulmonary artery
      pressure. We conclude that UP induce oxidative stress in vascular endothelial
      cells by activating NAD(P)H oxidase and the mitochondria. The endothelial
      oxidative stress may be an important mechanism for PM-induced acute
      cardiovascular health effects.

PMID- 16571864
TI  - Calsequestrin targeting to sarcoplasmic reticulum of skeletal muscle fibers.
AB  - Calsequestrin (CS) is the low-affinity, high-capacity calcium binding protein
      segregated to the lumen of terminal cisternae (TC) of the sarcoplasmic reticulum
      (SR). The physiological role of CS in controlling calcium release from the SR
      depends on both its intrinsic properties and its localization. The mechanisms of
      CS targeting were investigated in skeletal muscle fibers and C2C12 myotubes, a
      model of SR differentiation, with four deletion mutants of epitope
      (hemagglutinin, HA)-tagged CS: CS-HA24NH2, CS-HA2D, CS-HA3D, and CS-HAHT, a
      double mutant of the NH2 terminus and domain III. As judged by immunofluorescence
      of transfected skeletal muscle fibers, only the double CS-HA mutant showed a
      homogeneous distribution at the sarcomeric I band, i.e., it did not segregate to
      TC. As shown by subfractionation of microsomes derived from transfected skeletal
      muscles, CS-HAHT was largely associated to longitudinal SR whereas CS-HA was
      concentrated in TC. In C2C12 myotubes, as judged by immunofluorescence, not only
      CS-HAHT but also CS-HA3D and CS-HA2D were not sorted to developing SR.
      Condensation competence, a property referable to CS oligomerization, was
      monitored for the several CS-HA mutants in C2C12 myoblasts, and only CS-HA3D was
      found able to condense. Together, the results indicate that 1) there are at least
      two targeting sequences at the NH2 terminus and domain III of CS, 2) SR-specific
      target and structural information is contained in these sequences, 3)
      heterologous interactions with junctional SR proteins are relevant for
      segregation, 4) homologous CS-CS interactions are involved in the overall
      targeting process, and 5) different targeting mechanisms prevail depending on the
      stage of SR differentiation.

PMID- 16571867
TI  - Kv2 channels oppose myogenic constriction of rat cerebral arteries.
AB  - By hyperpolarizing arterial smooth muscle, voltage-gated, Ca2+-independent K+
      (Kv) channels decrease calcium influx and thus oppose constriction. However, the
      molecular nature of the Kv channels function in arterial smooth muscle remains
      controversial. Recent investigations have emphasized a predominant role of Kv1
      channels in regulating arterial tone. In this study, we tested the hypothesis Kv2
      channels may also significantly regulate tone of rat cerebral arteries. We found
      that Kv2.1 transcript and protein are present in cerebral arterial smooth muscle.
      In addition, our analysis indicates that a substantial component (approximately
      50%) of the voltage dependencies and kinetics of Kv currents in voltage-clamped
      cerebral arterial myocytes is consistent with Kv2 channels. Accordingly, we found
      that stromatoxin, a specific inhibitor of Kv2 channels, significantly decreased
      Kv currents in these cells. Furthermore, stromatoxin enhanced myogenic
      constriction of pressurized arterial segments. We also found that during
      angiotensin II-induced hypertension, Kv2 channel function was reduced in isolated
      myocytes and in intact arteries. This suggests that impaired Kv2 channel activity
      may contribute to arterial dysfunction during hypertension. On the basis of these
      novel observations, we propose a new model of Kv channel function in arterial
      smooth muscle in which Kv2 channels (in combination with Kv1 channels) contribute
      to membrane hyperpolarization and thus oppose constriction.

PMID- 16571866
TI  - Role of vimentin in smooth muscle force development.
AB  - Vimentin intermediate filaments undergo spatial reorganization in cultured smooth
      muscle cells in response to contractile activation; however, the role of vimentin
      in the physiological properties of smooth muscle has not been well elucidated.
      Tracheal smooth muscle strips were loaded with antisense oligonucleotides (ODNs)
      against vimentin and then cultured for 2 days to allow for protein degradation.
      Treatment with vimentin antisense, but not sense, ODNs suppressed vimentin
      protein expression; neither vimentin antisense nor sense ODNs affected protein
      levels of desmin and actin. Force development in response to ACh stimulation or
      KCl depolarization was lower in vimentin-deficient tissues than in vimentin sense
      ODN- or non-ODN-treated muscle strips. Passive tension was also depressed in
      vimentin-depleted muscle tissues. Vimentin downregulation did not attenuate
      increases in myosin light chain (MLC) phosphorylation in response to contractile
      stimulation or basal MLC phosphorylation. In vimentin sense ODN-treated or non
      ODN-treated smooth muscle strips, the desmosomal protein plakoglobin was
      primarily localized in the cell periphery. The membrane-associated localization
      of plakoglobin was reduced in vimentin-depleted muscle tissues. These studies
      suggest that vimentin filaments play an important role in mediating active force
      development and passive tension, which are not regulated by MLC phosphorylation.
      Vimentin downregulation impairs the structural organization of desmosomes, which
      may be associated with the decrease in force development.

PMID- 16571868
TI  - Src family kinases regulate p38 MAPK-mediated IL-6 production in Kupffer cells
      following hypoxia.
AB  - Tissue hypoxia is a common sequel of trauma-hemorrhage but can occur even without
      blood loss under hypoxic conditions. Although hypoxia is known to upregulate
      Kupffer cells (KC) to release cytokines, the precise mechanism of release remains
      unknown. We hypothesized that Src family kinases play a role in mediating KC
      mitogen-activated protein kinase (MAPK) signaling and their cytokine production
      after hypoxia. Male C3H/HeN mice received either Src inhibitor PP1 (1.5 mg/kg
      body wt) or vehicle 1 h before hypoxia. KCs were isolated 1 h after hypoxia,
      lysed, and immunoblotted with antibodies to Src, p38, ERK1/2, or JNK proteins. In
      addition, KCs were cultured to measure interleukin-6 (IL-6) and monocyte
      chemoattractant protein-1 (MCP-1) production. Hypoxia produced a significant
      increase in KC Src and MAPK (p38, ERK, JNK) activity compared with normoxic
      controls. This was associated with an increase in IL-6 and MCP-1 production.
      Treatment with PP1 abolished the increase in KC Src activation as well as p38
      activity. However, PP1 did not prevent the increase in KC ERK1/2 or JNK
      phosphorylation. Furthermore, administration of PP1 prevented the hypoxia-induced
      increase in IL-6 but not MCP-1 release by KC. Additional in vitro results suggest
      that p38 but not ERK1/2 or JNK are critical for KC IL-6 production. In contrast,
      the production of MCP-1 by KC was found to be independent of MAPK. Thus hypoxia
      increases KC IL-6 production by p38 MAPK activation via Src-dependent pathway.
      Src kinases may therefore be a novel therapeutic target for preventing immune
      dysfunction following low-flow conditions in trauma patients.

PMID- 16571869
TI  - Adenosine receptor expression and function in bladder uroepithelium.
AB  - The uroepithelium of the bladder forms an impermeable barrier that is maintained
      in part by regulated membrane turnover in the outermost umbrella cell layer.
      Other than bladder filling, few physiological regulators of this process are
      known. Western blot analysis established that all four adenosine receptors (A1,
      A2a, A2b, and A3) are expressed in the uroepithelium. A1 receptors were
      prominently localized to the apical membrane of the umbrella cell layer, whereas
      A2a, A2b, and A3 receptors were localized intracellularly or on the basolateral
      membrane of umbrella cells and the plasma membrane of the underlying cell layers.
      Adenosine was released from the uroepithelium, which was potentiated 10-fold by
      stretching the tissue. Administration of adenosine to the serosal or mucosal
      surface of the uroepithelium led to increases in membrane capacitance (where 1
      microF approximately 1 cm(2) tissue area) of approximately 30% or approximately
      24%, respectively, after 5 h. Although A1, A2a, and A3 selective agonists all
      stimulated membrane capacitance after being administrated serosally, only the A1
      agonist caused large increases in capacitance after being administered mucosally.
      Adenosine receptor antagonists as well as adenosine deaminase had no effect on
      stretch-induced capacitance increases, but adenosine potentiated the effects of
      stretch. Treatment with U-73122, 2-aminoethoxydiphenylborate, or xestospongin C
      or incubation in calcium-free Krebs solution inhibited adenosine-induced
      increases in capacitance. These data indicate that the uroepithelium is a site of
      adenosine biosynthesis, that adenosine receptors are expressed in the
      uroepithelium, and that one function of these receptors may be to modulate
      exocytosis in umbrella cells.

PMID- 16571870
TI  - Electrophysiological characterization of murine HL-5 atrial cardiomyocytes.
AB  - HL-5 cells are cultured murine atrial cardiomyocytes and have been used in
      studies to address important cellular and molecular questions. However,
      electrophysiological features of HL-5 cells have not been characterized. In this
      study, we examined such properties using whole cell patch-clamp techniques.
      Membrane capacitance of the HL-5 cells was from 8 to 62 pF. The resting membrane
      potential was -57.8 +/- 1.4 mV (n = 51). Intracellular injection of depolarizing
      currents evoked action potentials (APs) with variable morphologies in 71% of the
      patched cells. Interestingly, the incidence of successful, current-induced APs
      positively correlated with the hyperpolarizing degrees of resting membrane
      potentials (r = 0.99, P < 0.001). Only a few of the patched cells (4 of 51, 7.8%)
      exhibited spontaneous APs. The muscarinic agonist carbachol activated the
      acetylcholine-activated K(+) current and significantly shortened the duration of
      APs. Immunostaining confirmed the presence of the muscarinic receptor type 2 in
      HL-5 cells. The hyperpolarization-activated cation current (I(f)) was detected in
      39% of the patched cells. The voltage to activate 50% of I(f) channels was -73.4
      +/- 1.2 mV (n = 12). Voltage-gated Na(+), Ca(2+), and K(+) currents were observed
      in the HL-5 cells with variable incidences. Compared with the adult mouse
      cardiomyocytes, the HL-5 cells had prolonged APs and small outward K(+) currents.
      Our data indicate that HL-5 cells display significant electrophysiological
      heterogeneity of morphological appearance of APs and expression of functional ion
      channels. Compared with adult murine cardiomyocytes, HL-5 cells show an immature
      phenotype of cardiac AP morphology.

PMID- 16571871
TI  - Statins inhibit growth of human endometrial stromal cells independently of
      cholesterol availability.
AB  - Endometriosis is characterized by ectopic growth of endometrial tissues. Statins,
      inhibitors of 3-hydroxy-3methylglutaryl-coenzyme A reductase (HMGCR), have been
      shown to decrease proliferation of several mesenchymal tissues. Actions of
      statins may be related to decreased availability of cholesterol as well as
      intermediate metabolites of the mevalonate pathway downstream of HMGCR. This
      study was designed to evaluate effects of statins on growth of endometrial
      stromal cells and to investigate mechanisms of these effects. Human endometrial
      stromal cells were cultured in the absence and in the presence of serum and with
      or without mevastatin and simvastatin. DNA synthesis and viable cell numbers were
      determined. Effects of statins were also evaluated in the presence of mevalonate
      and squalene. Furthermore, effects on phosphorylation of mitogen-activated
      protein kinase 3/1 (MAPK3/1) (also known as extracellular signal-regulated kinase
      [ERK1/2]) were determined. Mevastatin and simvastatin induced a concentration
      dependent inhibition of DNA synthesis and viable cell count in chemically defined
      media and in the presence of serum. Mevalonate, but not squalene, abrogated
      inhibitory effects of statins on cell proliferation. Statins inhibited MAPK3/1
      phosphorylation. This is the first study demonstrating that statins inhibit
      growth of endometrial stromal cells. This effect is also demonstrable in the
      presence of a supply of cholesterol and may be related to decreased activation of
      MAPK3/1. The present observations may be relevant to potential therapeutic use of
      statins in conditions such as endometriosis.

PMID- 16571872
TI  - Large offspring or large placenta syndrome? Morphometric analysis of late
      gestation bovine placentomes from somatic nuclear transfer pregnancies
      complicated by hydrallantois.
AB  - Somatic nuclear transfer (NT) in cattle is often complicated by fetal oversize
      (i.e., large offspring syndrome), hydrallantois, and placentomegaly in late
      gestation. The aims of this work were to obtain data on the placentome structure
      in NT-recipient cows with hydrallantois (NTH) and to relate these with fetal and
      placental weights to better understand the abnormalities observed in NTH
      pregnancies during the third trimester. Pregnant cows were slaughtered between
      Gestation Days 180 and 280. The fetuses were weighed, and the placentomes were
      numbered and weighed. Placentomes were examined by histologic and stereological
      techniques. Macroscopic data showed that placental overgrowth preceded fetal
      overgrowth, and the ratio of the fetal to the total placentome weight in the NTH
      group was lower than that in controls after Gestation Day 220. This suggests that
      placental overgrowth is due to placental default rather than due to fetal
      overgrowth, as shown also by stereological analysis showing primary deregulation
      of the growth of cotyledonary tissues. Observed alterations, such as thinning of
      the maternal epithelium within placentomes and increased trophoblastic surface,
      could be secondary adaptations. Thus, placental growth deregulations would be due
      to modifications of the expression of placental factors. Various examples of
      placental deficiency were observed, suggesting that some fetal abnormalities
      observed in NTH calves, such as enlarged heart, enlarged umbilical cord, and
      abdominal ascites, are consequences of placental dysfunction. Therefore, the
      condition described by the term "large offspring syndrome" might better be
      described by "large placenta syndrome," because this syndrome affects an average
      of 50% of late-gestation NT pregnancies. No conclusion can be drawn from this
      work on apparently normal pregnancies.

PMID- 16571873
TI  - Membrane initiated estrogen signaling in breast cancer.
AB  - Recent research has focused on effects of the estrogen receptor acting at the
      level of the cell membrane in breast cancer. In this review we describe 17beta
      estradiol (E2)-initiated membrane signaling pathways involving the activation of
      several kinases that contribute to the regulation of cell proliferation and
      prevention of apoptosis. Although classical concepts had assigned priority to the
      nuclear actions of estrogen receptor, recent studies document the additional
      importance of estrogen receptor residing in or near the plasma membrane. A small
      fraction of estrogen receptor is associated with the cell membrane and mediates
      the rapid effects of E2. Unlike classical growth factor receptors, such as
      insulin-like growth factor 1 receptor (IGF1R) and epidermal growth factor
      receptor (EGFR), estrogen receptor has no transmembrane and kinase domains and is
      known to initiate E2 rapid signals by forming a protein complex with many
      signaling molecules. The formation of the protein complex is a critical step,
      leading to the activation of the MAPK1/3 (also known as MAP kinase) and AKT1
      (also known as Akt) pathways. A full understanding of the mechanisms underlying
      these relationships, with the ultimate aim of abrogating specific steps, should
      lead to more-targeted strategies for treatment of hormone dependent-breast
      cancer.

PMID- 16571874
TI  - Effect of vascular endothelial growth factor and testis tissue culture on
      spermatogenesis in bovine ectopic testis tissue xenografts.
AB  - Bovine ectopic testis tissue grafting is a technique that can be used to study
      bovine spermatogenesis and for the production of germ cells for a variety of
      applications. Approximately 10% of seminiferous tubule cross sections in testis
      grafts contain spermatids, providing a unique tool to investigate what regulates
      germ cell differentiation. We hypothesized that manipulation of testis tissue
      grafts would increase the percentage of seminiferous tubule cross sections
      undergoing complete germ cell differentiation. To test this hypothesis, bovine
      testis tissue was treated with vascular endothelial growth factor (VEGF) at the
      time of grafting or explant cultured for 1 wk prior to grafting. For the VEGF
      experiment, 8-wk donor tissue and graft sites were treated with 1 microg of VEGF
      in order to increase angiogenesis at the graft site. For the testis tissue
      culture experiment, 4-wk-old donor testis was cultured for 1 wk prior to grafting
      to stimulate spermatogonial stem cell proliferation. Testis tissue grafts were
      removed from the mice 24 wk after grafting. VEGF treatment increased graft weight
      and the percentage of seminiferous tubule cross sections with elongating
      spermatids at the time of graft removal. Cultured testis tissue grafts were
      smaller and had fewer seminiferous tubules per graft. However, there was no
      difference in the percentage of seminiferous tubule cross sections that contained
      any germ cell type between groups. These data indicate for the first time that
      bovine testis tissue can be manipulated to better support germ cell
      differentiation in grafted tissue.

PMID- 16571875
TI  - Shear stress induces preimplantation embryo death that is delayed by the zona
      pellucida and associated with stress-activated protein kinase-mediated apoptosis.
AB  - In this study, we discovered that embryos sense shear stress and sought to
      characterize the kinetics and the enzymatic mechanisms underlying induction of
      embryonic lethality by shear stress. Using a rotating wall vessel programmed to
      produce 1.2 dynes/cm2 shear stress, it was found that shear stress caused
      lethality within 12 h for E3.5 blastocysts. Embryos developed an approximate 100%
      increase in mitogen-activated protein kinase 8/9 (formerly known as stress
      activated protein kinase/junC kinase 1/2) phosphorylation by 6 h of shear stress
      that further increased to approximately 350% by 12 h. Terminal
      deoxynucleotidyltransferase dUTP nick end labeling/apoptosis was at baseline
      levels at 6 h and increased to approximately 500% of baseline at 12 h, when
      irreversible commitment to death occurred. A mitogen-activated protein kinase 8/9
      phosphorylation inhibitor, D-JNKI1, was able to inhibit over 50% of the
      apoptosis, suggesting a causal role for mitogen-activated protein kinase 8/9
      phosphorylation in the shear stress-induced lethality. The E2.5 (compacted eight
      cell/early morula stage) embryo was more sensitive to shear stress than the E3.5
      (early blastocyst stage) embryo. Additionally, zona pellucida removal
      significantly accelerated shear stress-induced lethality while having no lethal
      effect on embryos in the static control. In conclusion, preimplantation embryos
      sense shear stress, chronic shear stress is lethal, and the zona pellucida
      lessens the lethal and sublethal effects of shear stress. Embryos in vivo would
      not experience as high a sustained velocity or shear stress as induced
      experimentally here. Lower shear stresses might induce sufficient mitogen
      activated protein kinase 8/9 phosphorylation that would slow growth or cause
      premature differentiation if the zona pellucida were not intact.

PMID- 16571876
TI  - Images in clinical medicine. Enterobius vermicularis.

PMID- 16571877
TI  - Part "D" for "defective"--the Medicare drug-benefit chaos.

PMID- 16571878
TI  - Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine.
AB  - BACKGROUND: Influenza A (H5N1) viruses could cause a severe worldwide epidemic,
      with high attack rates, large numbers of deaths and hospitalizations, and wide
      disruption. Effective vaccines against these viruses in humans are urgently
      needed. METHODS: We conducted a multicenter, double-blind two-stage study
      involving 451 healthy adults 18 to 64 years of age who were randomly assigned in
      a 2:2:2:2:1 ratio to receive two intramuscular doses of a subvirion influenza A
      (H5N1) vaccine of 90, 45, 15, or 7.5 microg of hemagglutinin antigen or placebo.
      The subjects were followed for the safety analysis for 56 days. Serum samples
      obtained before each vaccination and again 28 days after the second vaccination
      were tested for H5 antibody by microneutralization and hemagglutination
      inhibition. RESULTS: Mild pain at the injection site was the most common adverse
      event for all doses of vaccine. The frequency of a serum antibody response was
      highest among subjects receiving doses of 45 microg or 90 microg. Among those who
      received two doses of 90 microg, neutralization antibody titers reached 1:40 or
      greater in 54 percent, and hemagglutination-inhibition titers reached 1:40 or
      greater in 58 percent. Neutralization titers of 1:40 or greater were seen in 43
      percent, 22 percent, and 9 percent of the subjects receiving two doses of 45, 15,
      and 7.5 microg, respectively. No responses were seen in placebo recipients.
      CONCLUSIONS: A two-dose regimen of 90 mug of subvirion influenza A (H5N1) vaccine
      does not cause severe side effects and, in the majority of recipients, generates
      neutralizing antibody responses typically associated with protection against
      influenza. A conventional subvirion H5 influenza vaccine may be effective in
      preventing influenza A (H5N1) disease in humans. (ClinicalTrials.gov number,
      NCT00115986.).

PMID- 16571879
TI  - Prevalence of monoclonal gammopathy of undetermined significance.
AB  - BACKGROUND: The prevalence of monoclonal gammopathy of undetermined significance
      (MGUS), a premalignant plasma-cell disorder, among persons 50 years of age or
      older has not been accurately determined. We used sensitive laboratory techniques
      to ascertain the prevalence of MGUS in a large population in a well-defined
      geographic area. METHODS: We identified all living residents of Olmsted County,
      Minnesota, as of January 1, 1995. We obtained serum that remained after the
      performance of routine clinical tests at Mayo Clinic or asked subjects for whom
      such serum was unavailable to provide a sample. Agarose-gel electrophoresis was
      performed on all serum samples, and any serum sample with a discrete band of
      monoclonal protein or thought to have a localized band was subjected to
      immunofixation. RESULTS: Serum samples were obtained from 21,463 of the 28,038
      enumerated residents 50 years of age or older (76.6 percent). MGUS was identified
      in 694 (3.2 percent) of these persons. Age-adjusted rates were higher in men than
      in women (4.0 percent vs. 2.7 percent, P<0.001). The prevalence of MGUS was 5.3
      percent among persons 70 years of age or older and 7.5 percent among those 85
      years of age or older. The concentration of monoclonal immunoglobulin was less
      than 1.0 g per deciliter in 63.5 percent and at least 2.0 g per deciliter in only
      4.5 percent of 694 persons. The concentration of uninvolved immunoglobulins was
      reduced in 27.7 percent of 447 persons tested, and 21.5 percent of 79 tested had
      a monoclonal urinary light chain. CONCLUSIONS: Among residents of Olmsted County,
      Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and
      5.3 percent of persons 70 years of age or older.

PMID- 16571880
TI  - Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like
      2.
AB  - Contactin-associated protein-like 2 (CASPR2) is encoded by CNTNAP2 and clusters
      voltage-gated potassium channels (K(v)1.1) at the nodes of Ranvier. We report a
      homozygous mutation of CNTNAP2 in Old Order Amish children with cortical
      dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon
      reflexes. Intractable focal seizures began in early childhood, after which
      language regression, hyperactivity, impulsive and aggressive behavior, and mental
      retardation developed in all children. Resective surgery did not prevent the
      recurrence of seizures. Temporal-lobe specimens showed evidence of abnormalities
      of neuronal migration and structure, widespread astrogliosis, and reduced
      expression of CASPR2.

PMID- 16571881
TI  - Behavioral health insurance parity for federal employees.
AB  - BACKGROUND: To improve insurance coverage of mental health and substance-abuse
      services, the Federal Employees Health Benefits (FEHB) Program offered mental
      health and substance-abuse benefits on a par with general medical benefits
      beginning in January 2001. The plans were encouraged to manage care. METHODS: We
      compared seven FEHB plans from 1999 through 2002 with a matched set of health
      plans that did not have benefits on a par with mental health and substance-abuse
      benefits (parity of mental health and substance-abuse benefits). Using a
      difference-in-differences analysis, we compared the claims patterns of matched
      pairs of FEHB and control plans by examining the rate of use, total spending, and
      out-of-pocket spending among users of mental health and substance-abuse services.
      RESULTS: The difference-in-differences analysis indicated that the observed
      increase in the rate of use of mental health and substance-abuse services after
      the implementation of the parity policy was due almost entirely to a general
      trend in increased use that was observed in comparison health plans as well as
      FEHB plans. The implementation of parity was associated with a statistically
      significant increase in use in one plan (+0.78 percent, P<0.05) a significant
      decrease in use in one plan (-0.96 percent, P<0.05), and no significant
      difference in use in the other five plans (range, -0.38 percent to +0.23 percent;
      P>0.05 for each comparison). For beneficiaries who used mental health and
      substance-abuse services, spending attributable to the implementation of parity
      decreased significantly for three plans (range, -201.99 dollars to -68.97
      dollars; P<0.05 for each comparison) and did not change significantly for four
      plans (range, -42.13 dollars to +27.11 dollars; P>0.05 for each comparison). The
      implementation of parity was associated with significant reductions in out-of
      pocket spending in five of seven plans. CONCLUSIONS: When coupled with management
      of care, implementation of parity in insurance benefits for behavioral health
      care can improve insurance protection without increasing total costs.

PMID- 16571882
TI  - Hereditary proteinuria syndromes and mechanisms of proteinuria.

PMID- 16571883
TI  - Images in clinical medicine. Bilateral renal-vein thrombosis associated with the
      nephrotic syndrome.

PMID- 16571884
TI  - Case records of the Massachusetts General Hospital. Case 10-2006. A 66-year-old
      woman with Barrett's esophagus with high-grade dysplasia.

PMID- 16571885
TI  - Vaccines against avian influenza--a race against time.

PMID- 16571886
TI  - Better behavioral health care coverage for everyone.

PMID- 16571887
TI  - Targeting rickettsia.

PMID- 16571888
TI  - Lethal avian influenza A (H5N1) infection in a pregnant woman in Anhui Province,
      China.

PMID- 16571889
TI  - Influenza vaccination and false positive HIV results.

PMID- 16571890
TI  - Oseltamivir resistance in influenza A (H5N1) infection.

PMID- 16571891
TI  - Infliximab for ulcerative colitis.

PMID- 16571892
TI  - Clinical trials report card.

PMID- 16571893
TI  - Community-acquired bacterial meningitis.

PMID- 16571894
TI  - Case 37-2005: a man with cardiac arrest while sleeping.

PMID- 16571895
TI  - Medical mystery: concentric calcification--the answer.

PMID- 16571896
TI  - Informatics-assisted protein profiling in a transgenic mouse model of amyotrophic
      lateral sclerosis.
AB  - One of the causes of amyotrophic lateral sclerosis (ALS) is due to mutations in
      Cu,Zn-superoxide dismutase (SOD1). The mutant protein exhibits a toxic gain of
      function that adversely affects the function of neurons in the spinal cord, brain
      stem, and motor cortex. A proteomic analysis of protein expression in a widely
      used mouse model of ALS was undertaken to identify differences in protein
      expression in the spinal cords of mice expressing a mutant protein with the G93A
      mutation found in human ALS. Protein profiling was done on soluble and
      particulate fractions of spinal cord extracts using high throughput two
      dimensional liquid chromatography coupled to tandem mass spectrometry. An
      integrated proteomics-informatics platform was used to identify relevant
      differences in protein expression based upon the abundance of peptides identified
      by database searching of mass spectrometry data. Changes in the expression of
      proteins associated with mitochondria were particularly prevalent in spinal cord
      proteins from both mutant G93A-SOD1 and wild-type SOD1 transgenic mice. G93A-SOD1
      mouse spinal cord also exhibited differences in proteins associated with
      metabolism, protein kinase regulation, antioxidant activity, and lysosomes. Using
      gene ontology analysis, we found an overlap of changes in mRNA expression in
      presymptomatic mice (from microarray analysis) in three different gene
      categories. These included selected protein kinase signaling systems, ATP-driven
      ion transport, and neurotransmission. Therefore, alterations in selected cellular
      processes are detectable before symptomatic onset in ALS mouse models. However,
      in late stage disease, mRNA expression analysis did not reveal significant
      changes in mitochondrial gene expression but did reveal concordant changes in
      lipid metabolism, lysosomes, and the regulation of neurotransmission. Thus,
      concordance of proteomic and mRNA expression data within multiple categories
      validates the use of gene ontology analysis to compare different types of "omic"
      data.

PMID- 16571897
TI  - Local flexibility in molecular function paradigm.
AB  - It is generally accepted that the functional activity of biological
      macromolecules requires tightly packed three-dimensional structures. Recent
      theoretical and experimental evidence indicates, however, the importance of
      molecular flexibility for the proper functioning of some proteins. We examined
      high resolution structures of proteins in various functional categories with
      respect to the secondary structure assessment. The latter was considered as a
      characteristic of the inherent flexibility of a polypeptide chain. We found that
      the proteins in functionally competent conformational states might be comprised
      of 20-70% flexible residues. For instance, proteins involved in gene regulation,
      e.g. transcription factors, are on average largely disordered molecules with over
      60% of amino acids residing in "coiled" configurations. In contrast, oxygen
      transporters constitute a class of relatively rigid molecules with only 30% of
      residues being locally flexible. Phylogenic comparison of a large number of
      protein families with respect to the propagation of secondary structure
      illuminates the growing role of the local flexibility in organisms of greater
      complexity. Furthermore the local flexibility in protein molecules appears to be
      dependent on the molecular confinement and is essentially larger in extracellular
      proteins.

PMID- 16571898
TI  - Adduct-specific monoclonal antibodies for the measurement of cisplatin-induced
      DNA lesions in individual cell nuclei.
AB  - The anticancer drug cisplatin executes its cytotoxic activity via formation of
      intra- and interstrand crosslinks in DNA. The relative contribution of
      structurally defined cisplatin adducts to induce apoptosis and the cellular
      processing of these lesions is still poorly understood mostly due to the lack of
      sensitive analytical tools for in vivo studies. Here we describe a new method to
      establish and characterize monoclonal antibodies (Mab) for structurally defined
      DNA adducts. The two major reaction products of cisplatin, the guanine-guanine
      (Pt-[GG]) and adenine-guanine (Pt-[AG]) intrastrand crosslinks are recognized by
      Mab R-C18 and R-B3, respectively. Both antibodies were employed in an immuno
      cytological assay allowing the quantification of drug-induced lesions in
      individual cell nuclei at clinically relevant doses. Analyzing various tissues of
      cisplatin-treated C57Bl/6 mice the accumulation of Pt-(GG) was highest in kidney
      tubular cells compared with 30, 50 and 90% lower levels in kidney stroma, liver
      and peripheral blood cells, respectively. Adduct kinetics revealed that wild type
      mouse cells remove up to 80% of the crosslinks in contrast to their complete
      persistence in nucleotide excision repair-deficient (XPC-/-) mice. The aptitude
      of the immunoassay for human molecular dosimetry studies was demonstrated by
      measuring adduct levels in tumor biopsies from patients treated with cisplatin.

PMID- 16571905
TI  - Intentional switches between bimanual coordination patterns are primarily
      effectuated by the nondominant hand.
AB  - Based on indications that hand dominance is characterized by asymmetrical
      interlimb coupling strength (with the dominant hand exerting stronger influences
      on the nondominant hand than vice versa), intentional switches between rhythmic
      bimanual coordination patterns were predicted to be mediated primarily by phase
      adaptations in the movements of the nondominant hand. This hypothesis was
      supported for both right-handed and left-handed participants who performed
      voluntary switches from in-phase to antiphase coordination and vice versa, at
      four different frequencies. In accordance with previous indications that
      handedness is expressed less consistently in left-handers, the asymmetry between
      the hands was less pronounced in left-handed than in right-handed participants.
      The asymmetry was smaller for switches from in-phase to antiphase coordination
      (i.e., in the direction opposite to spontaneous transitions) than for switches in
      the reverse direction, suggesting that (the expression of) the handedness-related
      asymmetry in coupling strength was weakened by intentional processes associated
      with these switches.

PMID- 16571906
TI  - Voluntary and involuntary postural responses to imposed optic flow.
AB  - We demonstrated that postural responses to imposed optic flow are to some extent
      voluntary. In a moving room, participants either stood normally or were
      instructed to resist any influence of visible motion on their stance. When
      participants attempted to resist, coupling of body sway with motion of the room
      was significantly greater than when the eyes were closed, but was significantly
      reduced relative to coupling in the normal stance condition. The results indicate
      that the use of imposed optic flow for postural control is not entirely automatic
      or involuntary. This conclusion motivates a search for non-perceptual factors
      that may influence the degree to which body sway is coupled to imposed optic
      flow.

PMID- 16571907
TI  - The visual regulation of goal-directed reaching movements in adults with Williams
      syndrome, Down syndrome, and other developmental delays.
AB  - Williams syndrome (WS) is a genetic disorder that causes general cognitive and
      developmental delays. Compared to persons with Down syndrome (DS) at the same
      developmental level, individuals with WS generally exhibit superior expressive
      language abilities, but have difficulty with tasks that require the visual
      control of movement. Recently it has been suggested that this latter problem
      reflects a deficit in dorsal stream function. In the present study, this
      hypothesis was investigated by examining the kinematics of rapid aiming
      movements. The performance of the participants with WS (n=4) was compared to the
      performance of participants with DS (n=8), with undifferentiated developmental
      delays (n=8), and from the general population (n=8). In partial support of the
      dorsal deficit hypothesis, the results suggest that, compared to people from the
      other groups, the participants with WS had difficulty in preparing their
      movements on the basis of the visual and other information available to them.
      This was particularly evident in their inability to properly scale movement
      velocities to the amplitude of the movements and in the number of discrete
      corrections made during movement execution.

PMID- 16571909
TI  - Impact of the visual environment on the execution of aimed movements.
AB  - The present study showed that movement execution depends on the direct visual
      environment. We replicated findings of an earlier study that showed a difference
      between real time information via a trace of the unfolding trajectory, and cursor
      feedback constituting real time information about the changing movement location.
      Detailed analyses involving subdividing a movement into four successive sections
      revealed that movements governed by trace feedback were typically slower and
      required more feedback guidance near the occurrence of peak velocity. The present
      study further showed that movement behavior under the two visual modes diverged
      even more due to the presence of a static object positioned within the action
      area of the movement. Movements in the trace feedback condition were affected by
      the presence of an object in the second half of the movement trajectory when the
      movement reached peak deceleration. Discussion focuses on the differences between
      the two modes of online visual information.

PMID- 16571908
TI  - Neural basis subserving the detection of postural instability: an fMRI study.
AB  - Human upright posture is a product of a complex dynamic system that relies on
      integration of input from multimodal sensory sources. Extensive research has
      explored the role of visual, vestibular, and somatosensory systems in the control
      of upright posture. However, the role of higher cognitive function in a
      participant's assessment of postural stability has been less studied. In previous
      research, we showed specific neural activation patterns in EEG associated with
      recognition of unstable postures in young healthy participants. Similar EEG
      patterns have been recently observed in regulation of posture equilibrium in
      dynamic stances. This article evaluates participants' postural stability in
      dynamic stances and neural activation patterns underlying visual recognition of
      unstable postures using event-related functional MRI (fMRI). Our results show
      that the "stable" participants were successful in recognition of unstable
      postures of a computer-animated body model and experienced egocentric motion.
      Successful recognition of unstable postures in these participants induces
      activation of distinct areas of the brain including bilateral parietal cortex,
      anterior cingulate cortex, and bilateral cerebellum. In addition, significant
      activation is observed in basal ganglia (caudate nucleus and putamen) but only
      during perception of animated postures. Our findings suggest the existence of
      modality-specific distributed activation of brain areas responsible for detection
      of postural instability.

PMID- 16571899
TI  - Novel GC-rich DNA-binding compound produced by a genetically engineered mutant of
      the mithramycin producer Streptomyces argillaceus exhibits improved
      transcriptional repressor activity: implications for cancer therapy.
AB  - The aureolic acid antibiotic mithramycin (MTM) binds selectively to GC-rich DNA
      sequences and blocks preferentially binding of proteins, like Sp1 transcription
      factors, to GC-rich elements in gene promoters. Genetic approaches can be applied
      to alter the MTM biosynthetic pathway in the producing microorganism and obtain
      new products with improved pharmacological properties. Here, we report on a new
      analog, MTM SDK, obtained by targeted gene inactivation of the ketoreductase MtmW
      catalyzing the last step in MTM biosynthesis. SDK exhibited greater activity as
      transcriptional inhibitor compared to MTM. SDK was a potent inhibitor of Sp1
      dependent reporter activity and interfered minimally with reporters of other
      transcription factors, indicating that it retained a high degree of selectivity
      toward GC-rich DNA-binding transcription factors. RT-PCR and microarray analysis
      showed that SDK repressed transcription of multiple genes implicated in critical
      aspects of cancer development and progression, including cell cycle, apoptosis,
      migration, invasion and angiogenesis, consistent with the pleiotropic role of Sp1
      family transcription factors. SDK inhibited proliferation and was a potent
      inducer of apoptosis in ovarian cancer cells while it had minimal effects on
      viability of normal cells. The new MTM derivative SDK could be an effective agent
      for treatment of cancer and other diseases with abnormal expression or activity
      of GC-rich DNA-binding transcription factors.

PMID- 16571910
TI  - Down-regulation of endogenous Wt1 expression by Sry transgene in the murine
      embryonic mesonephros-derived M15 cell line.
AB  - Wt1 is one of numerous candidate genes comprising the hypothetical chain of gene
      expression essential for male sex differentiation of the bipotential indifferent
      gonads during embryogenesis. However, the evidence in the literature is
      ambivalent regarding the position of Wt1 relative to Sry in this scheme; Wt1
      might act either upstream or downstream of Sry. In the present study, the effects
      of Sry expression upon Wt1 were investigated using M15 cells (XX karyotype),
      which are derived from murine embryonic mesonephros and express endogenous Wt1.
      In 3 stably-transformed Sry-expressing M15 cell lines, we showed that the
      expression levels of the mRNAs coding for all 4 isoforms of the WT1 proteins were
      down-regulated. Similarly, Wnt 4 expression was down-regulated in these cell
      lines. Silencing of Sry in the transformed cell lines using ribozymes or short
      hairpin RNAs (shRNAs) resulted in elevated levels of Wt1 and Wnt4 expression.
      These results strongly indicate that Wt1 might be under the control of Sry during
      gonadal differentiation in the mouse. In electrophoretic mobility shift assays
      (EMSA), we demonstrated that the 3.7 kb 5'-upstream DNA stretch of Wt1 containing
      potential Sry binding sites was capable of forming molecular complexes with
      nuclear protein(s) from Sry expressing cells but not with those from control non
      Sry expressing cells. In summary, our present results support the notion that Wt1
      is located downstream of Sry and down-regulated by the sex determining gene.
      Although the precise biological meaning of the present findings have yet to be
      clarified, it is possible that Wt1 plays a dual role during gonadal
      differentiation, i. e., turning on Sry expression on one hand, and being down
      regulated by its product, Sry, on the other, possibly forming a type of negative
      feed-back mechanism. Further work is needed to substantiate this view.

PMID- 16571911
TI  - Expression and subcellular localization of GSE protein in germ cells and
      preimplantation embryos.
AB  - We previously identified a novel gonad-specific expression gene (Gse) and
      investigated its expression during gametogenesis in the mouse testis and ovary.
      In this study, we generated a polyclonal antibody to GSE protein and determined
      the profiles of the protein's expression in germ cells and preimplantation
      embryos in detail using immunocytochemical and immunofluorescence staining. In a
      Western blot analysis, the anti-GSE antibody recognized long and short isoforms
      (approximately 27.6 kDa and 23.1 kDa) of the protein in the mouse testis and the
      long isoform in the ovary. In the mouse testis, GSE protein was expressed in
      spermatocytes I in the pachytene stage, round spermatids, and elongated
      spermatids. In the mouse ovary, the protein was located in the cytoplasm and
      nucleus of all oocytes regardless of the stage of the ovarian follicles. In
      preimplantation embryos from the pronuclear to blastocyst stage, however, GSE
      protein was mainly detected in the nuclei of cells. At the blastocyst stage, the
      protein was confirmed to have accumulated in the inner cell mass (ICM), whereas
      it had mostly disappeared from the trophectoderm (TE). These findings suggest
      that GSE protein may play a role in the establishment of nuclear totipotency and
      may be associated with early lineage specification.

PMID- 16571912
TI  - Expression pattern of alphavbeta3 and alphavbeta5 integrin mRNA in mouse fetal
      gonads.
AB  - The alphavbeta3 and alphavbeta5 integrins are known as transmembrane receptors
      capable of binding to the RGD amino acid peptide sequence. In mouse early
      gonadogenesis, some proteins containing the RGD sequence are deposited into
      extracellular space and participate in morphogenesis. We analyzed the expression
      patterns of the alphavbeta3 and alphavbeta5 integrins in mouse developing gonads
      (10.5-13.5 days post coitum) using whole-mount in situ hybridization. The alphav
      integrin mRNA was homogenously expressed in developing gonadal regions. On the
      other hand, the beta3 integrin mRNA was found only in large and round cells
      (presumptive germ cells), whereas beta5 integrin was localized in gonadal somatic
      cells, with the exception of coelomic epithelial cells. The beta3 integrin
      expressed cells were determined to be primordial germ cells because the number of
      these cells was drastically reduced in busulfan-treated gonads. In this study, we
      demonstrated that the alphavbeta3 and alphavbeta5 integrins are widely localized
      in the mouse developing gonads and discussed their presumptive functions on mouse
      gonadogenesis.

PMID- 16571913
TI  - Sucralfate protects intestinal epithelial cells from radiation-induced apoptosis
      in rats.
AB  - Radiotherapy for malignant pelvic disease is often followed by acute radiation
      colitis (ARC). It has been reported that sucralfate treatment has a protective
      effect against ARC, though the mechanisms of action are unknown. The effects of
      sucralfate on X-ray radiation-induced apoptosis was studied at 4 Gy in the
      colonic crypt cells of rats. Sucralfate enemas given prior to radiation resulted
      in the following: (1) reduction in number of apoptotic colonic crypt cells; (2)
      reduction in number of caspase-3 positive cells; (3) decreases in p53
      accumulation and p21 expression; (4) decreases of Bax/Bcl-2 ratio. The protective
      effects of sucralfate against ARC may be partially due to the suppression of
      radiation-induced apoptosis by way of p53 in the colon and the protection of the
      colonic epithelial stem cell region.

PMID- 16571914
TI  - Altered immune cell proportions in the radiodermatitis induced hairless mice-1
      (HR-1).
AB  - Accidental radiation exposures or radiation therapy can cause internal and
      external damage including radiodermatitis. Even though radiodermatitis is one of
      the dose limiting factors in radiotherapy, the immunological nature of it is not
      yet been clearly understood. In this study, we have examined the alteration in
      immune cell population during the radiodermatitis process. A radiodermatitis
      model was established in HR-1 mice by locally exposing a posterior dorsal region
      to 10 Gy X-ray/day for 4 consecutive days. Collagen accumulation, redness,
      erythema, and dry desquamation of the skin were detected after X-irradiation. The
      size and total cell number of the spleen decreased immediately after X
      irradiation, compared to those of the sham-irradiated mice, and recovered to the
      normal levels two weeks later. Reduction and recovery of the bone marrow cell
      population preceded a similar change of the spleen cell population. The
      proportion of CD4+ T cell increased, while the proportion of CD8+ T cell
      decreased ahead of the obvious skin damage, in both lymph node and spleen of the
      irradiated mice. Interestingly, the proportion of splenic monocytes/macrophages
      was expanded gradually at a similar kinetics with the aggravation of the
      radiodermatitis. The infiltration of the CD11b+ monocyte/macrophage to the X
      irradiated skin also coincided with the development of radiodermatitis. These
      altered proportions of immune cells may play important roles in radiodermatitis.

PMID- 16571915
TI  - Effects of ceramide inhibition on radiation-induced apoptosis in human leukemia
      MOLT-4 cells.
AB  - In the present study, using inhibitors of ceramide synthase (fumonisin B1),
      ketosphinganine synthetase (L-cycloserine), acid sphingomyelinase (D609 and
      desipramine) and neutral sphingomyelinase (GW4869), the role of ceramide in X-ray
      induced apoptosis was investigated in MOLT-4 cells. The diacylglycerol kinase
      (DGK) assay showed that the intracellular concentration of ceramide increased
      time-dependently after X irradiation of cells, and this radiation-induced
      accumulation of ceramide did not occur prior to the appearance of apoptotic
      cells. Treatment with D609 significantly inhibited radiation-induced apoptosis,
      but did not inhibit the increase of intracellular ceramide. Treatment with
      desipramine or GW4869 prevented neither radiation-induced apoptosis nor the
      induced increase of ceramide. On the other hand, fumonisin B1 and L-cycloserine
      had no effect on the radiation-induced induction of apoptosis, in spite of
      significant inhibition of the radiation-induced ceramide. From these results, it
      was suggested that the increase of the intracellular concentration of ceramide
      was not essential for radiation-induced apoptosis in MOLT-4 cells.

PMID- 16571917
TI  - Dose-response and large relative biological effectiveness of fast neutrons with
      regard to mouse fetal cerebral neuron apoptosis.
AB  - To evaluate the relative biological effectiveness (RBE) of low doses of neutrons
      on fetal nervous development, [C57BL/6J x C3H/He] hybrid (B6C3F1) mice were
      exposed to cyclotron-derived fast neutrons with peak energy of 10 MeV (0.02-1.0
      Gy) or 137Cs-generated gamma-rays (0.1-2.0 Gy) on embryonic day 13.5. We then
      evaluated the incidence of neuronal apoptosis in the cerebral cortex 24 hours
      after irradiation. Neuronal apoptosis increased in a dose-dependent manner in
      both neutron- and gamma-ray-irradiated groups: even at the lowest dose, a minimal
      increase in the apoptotic index was noted in response to both types of radiation.
      The dose-response curves were best fitted to linear quadratic models, and the
      evaluated RBE was 9.8, which was considered to be large for a prenatal effect and
      acute tissue injury induced by a low dose of neutrons.

PMID- 16571918
TI  - A pathology study of malignant and benign ovarian tumors among atomic-bomb
      survivors--case series report.
AB  - The present article describes the series of incident primary ovarian tumors in
      the Life Span Study (LSS) cohort of the Radiation Effects Research Foundation,
      with particular emphasis on case ascertainment and characterization of
      histological features of the tumors. We identified 723 ovarian tumors (260
      malignant, 463 benign) in 648 individuals of about 70,000 female LSS subjects; 71
      cases had more than one ovarian tumor. We histologically confirmed 601 tumors
      (182 malignant, 419 benign tumors). The most frequent histological type was
      common epithelial tumor (90.7% for malignant and 59.7% for benign tumors). The
      distributions of ovarian tumors by histological type were similar to those from
      other studies. Among malignancies, the frequency of common epithelial types
      relative to other tumor types increased with radiation dose (p = 0.02). Among
      benign tumors, the relative frequency of sex-cord stromal tumors increased with
      radiation dose (p = 0.04). The women with mucinous cancer had better survival
      than those with serous cancers (p = 0.03). Within tumor types, there was no
      consistent pattern of survival by radiation dose. Variations in histological
      types of ovarian tumors in response to radiation dose, suggested by the case
      series data need to be followed up by population-based incidence analysis.

PMID- 16571916
TI  - Application of unfolding technique to HPGe detector using response functions
      calculated with the EGS4 Monte Carlo code.
AB  - The EGS4 Monte Carlo simulation technique was used to obtain the energy spectra
      of photons arriving at a detector from the pulse height distributions measured by
      the same detector. First, the measured pulse height distribution for incident
      photons from several radiation sources such as 60Co, 137Cs, 152Eu and 207Bi with
      a collimator are compared with those calculated using the EGS4 code to
      investigate the feasibility of the simulation. The comparison showed good
      agreement of 98.7% for 60Co, 92.5% for 207Bi on the total counts. Second, the
      pulse height distributions were measured in the open space and then unfolded. The
      measurement of the distributions was done with changing the source to detector
      distance (SDD) from 10 cm to 100 cm for 60Co and 137Cs respectively. In the
      unfolding process, response functions of a high purity Ge (HPGe) detector were
      calculated using the EGS4 code. The calculated pulse height distributions were
      then normalized to the measured ones at the peaks of the incident photon
      energies. The ratio of the sum of counts of the main peaks to the total count in
      the unfolded spectra for 60Co varied from 5.4 to 5.7 times greater than those in
      the measured pulse height distributions, while from 2.5 to 2.9 times for 137Cs.
      Electron contribution to the unfolded spectra for 137Cs decreased as the source
      to detector distance increased, becoming negligible above 50 cm. The pulse height
      distributions at the center of the reference plane at 100 cm from the 60Co and
      137Cs dummy sources located inside each irradiator were also measured and
      unfolded to obtain the real pulse height distribution. In the unfolded spectra,
      the photons scattered from the surrounding materials were reduced to
      approximately one fourth of those measured in the open space due to the small
      size of apertures of the irradiators. The ratio of the sum of counts for the main
      peaks to the total count was larger than those in the measured pulse height
      distributions by the factor of 5.0 for 60Co and 3.4 for 137Cs. The uncertainties
      estimated in the unfolding processes were around 0.1% for 60Co and 0.07% for
      137Cs.

PMID- 16571920
TI  - Monte Carlo simulation of water radiolysis for low-energy charged particles.
AB  - The paper describes the development of chemical modules simulating the
      prechemical and chemical stages of charged particle tracks in pure liquid water.
      These calculations are based on our physical track structure codes for electrons
      and ions (KURBUC, LEPHIST and LEAHIST) which provide the initial spatial
      distribution of H2O+, H2O* and subexcitation electrons at approximately 10(-15)
      s. We considered 11 species and 26 chemical reactions. A step-by-step Monte Carlo
      approach was adopted for the chemical stage between 10(-12) s and 10(-6) s. The
      chemistry codes enabled to simulate the non-homogeneous chemistry that pertains
      to electron, proton and alpha-particle tracks of various linear energy transfers
      (LET). Time-dependent yields of chemical species produced by electrons and ions
      of different energies were calculated. The calculated primary yields (G values at
      10(-6) s) of 2.80 for OH and 2.59 for e(aq)- for 1 MeV electrons are in good
      agreement with the published values. The calculated G values at 10(-6) s for a
      wide range LETs from of 0.2 to 235 keV microm(-1) were obtained. The calculations
      show the LET dependence for OH and H2O2. The electron penetration ranges were
      calculated in order to discuss the role of low energy electrons.

PMID- 16571919
TI  - Protective effect of triphlorethol-A from Ecklonia cava against ionizing
      radiation in vitro.
AB  - We studied the cytoprotective effect of triphlorethol-A against gamma-ray
      radiation-induced oxidative stress. In this study, hydrogen peroxide, which is a
      reactive oxygen species (ROS), was detected using 2',7'
      dichlorodihydrofluorescein diacetate (DCF-DA) assay. Triphlorethol-A reduced
      intracellular hydrogen peroxide generated by gamma-ray radiation. This compound
      provided protection against radiation-induced membrane lipid peroxidation and
      cellular DNA damage which are the main targets of radiation-induced damage.
      Triphlorethol-A protected the cell viability damaged by the radiation through
      inhibition of apoptosis. Triphlorethol-A reduced the expression of bax and
      activated caspase 3 induced by radiation, but recovered the expression of bcl-2
      decreased by radiation. Taken together, the results suggest that triphlorethol-A
      protects cells against oxidative damage induced by radiation through reducing
      ROS.

PMID- 16571921
TI  - p27Cip/Kip is involved in hsp25 or inducible hsp70 mediated adaptive response by
      low dose radiation.
AB  - Thermoresistant (TR) clone of radiation-induced fibrosarcoma (RIF) cells have
      been reported to show adaptive response to 1 cGy of low dose radiation, and hsp25
      and inducible hsp70 are involved in this process. In the present study, to
      further elucidate the mechanism of how hsp25 and inducible hsp70 regulate the
      adaptive response, hsp25 or inducible hsp70 overexpressed RIF cells were
      irradiated with 1 cGy and cell cycle was analyzed. Hsp25 or inducible hsp70
      overexpressed cells as well as TR cells showed increase of G1 phase population
      after gamma-irradiation at 1 cGy, while the parent RIF cells did not. [3H]
      Thymidine and BrdU incorporation also indicated that both hsp25 and inducible
      hsp70 were involved in G1 arrest after 1 cGy irradiation. Molecular analysis
      revealed upregulation of p27Cip/Kip protein in hsp25 and inducible hsp70
      overexpressed cells, and cotransfection of p27Cip/Kip antisense abolished the
      induction of adaptive response and 1 cGy-mediated G1 arrest. The above results
      indicate that induction of adaptive response by hsp25 and inducible hsp70 is
      mediated by upregulation of p27Cip/Kip protein, resulting in low dose radiation
      induced G1 arrest.

PMID- 16571922
TI  - Vitamin E and L-carnitine, separately or in combination, in the prevention of
      radiation-induced oral mucositis and myelosuppression: a controlled study in a
      rat model.
AB  - The aim of this study was to determine the effects of vitamin E (VE) and L
      carnitine (LC) supplementation, separately or in combination, on radiation
      induced oral mucositis and myelosuppression. Group 1 received no treatment
      (control). Group 2 received 15 Gray of 60Co gamma irradiation as a single dose to
      total cranium (IR). Group 3, 4, and 5 received irradiation plus 40 mg/kg/day VE
      (IR+VE) or 200 mg/kg/day LC (IR+LC) or in combination (IR+VE+LC) respectively.
      Clinically and histopathologically, assessments of mucosal reactions were
      performed by two independent experts in Radiation Oncology and Pathology,
      respectively. Hematologic analyses and antioxidant enzyme evaluations were also
      performed. Irradiation significantly increased oral mucositis, and decreased
      thrombocyte and White Blood Cell counts. A significant increase in
      malondialdehyde (MDA) levels and decrease in superoxide dismutase (SOD) and
      catalase (CAT) activities in plasma were found in the IR group. VE and LC
      administration, separately, plus irradiation significantly delayed the starting
      day, and reduced the severity of, oral mucositis. This administration also
      reduced a fall in the numbers of thrombocyte and WBC caused by irradiation, and
      decreased the MDA level, and increased the activity of SOD and CAT enzymes in the
      plasma. VE and LC, in combination, plus irradiation did not provide a superior
      radioprotection against radiation-induced toxicities.

PMID- 16571923
TI  - Around Semipalatinsk nuclear test site: progress of dose estimations relevant to
      the consequences of nuclear tests (a summary of 3rd Dosimetry Workshop on the
      Semipalatinsk nuclear test site area, RIRBM, Hiroshima University, Hiroshima, 9
      11 of March, 2005).
AB  - The paper is an analytical overview of the main results presented at the 3rd
      Dosimetry Workshop in Hiroshima(9-11 of March 2005), where different aspects of
      the dose reconstruction around the Semipalatinsk nuclear test site(SNTS) were
      discussed and summarized. The results of the international intercomparison of the
      retrospective luminescence dosimetry(RLD) method for Dolon' village(Kazakhstan)
      were presented at the Workshop and good concurrence between dose estimations by
      different laboratories from 6 countries (Japan, Russia, USA, Germany, Finland and
      UK) was pointed out. The accumulated dose values in brick for a common depth of
      10mm depth obtained independently by all participating laboratories were in good
      agreement for all four brick samples from Dolon' village, Kazakhstan, with the
      average value of the local gamma dose due to fallout (near the sampling
      locations) being about 220 mGy(background dose has been subtracted).Furthermore,
      using a conversion factor of about 2 to obtain the free-in-air dose, a value of
      local dose approximately 440 mGy is obtained, which supports the results of
      external dose calculations for Dolon': recently published soil contamination
      data, archive information and new models were used for refining dose calculations
      and the external dose in air for Dolon village was estimated to be about 500 mGy.
      The results of electron spin resonance(ESR) dosimetry with tooth enamel have
      demonstrated the notable progress in application of ESR dosimetry to the problems
      of dose reconstruction around the Semipalatinsk nuclear test site. At the present
      moment, dose estimates by the ESR method have become more consistent with
      calculated values and with retrospective luminescence dosimetry data, but
      differences between ESR dose estimates and RLD/calculation data were noted. For
      example mean ESR dose for eligible tooth samples from Dolon' village was
      estimated to be about 140 mGy(above background dose), which is less than dose
      values obtained by RLD and calculations. A possible explanation of the
      differences between ESR and RLD/calculations doses is the following: for
      interpretation of ESR data the "shielding and behaviour" factors for investigated
      persons should be taken into account. The "upper level" of the combination of
      "shielding and behaviour" factors of dose reduction for inhabitants of Dolon'
      village of about 0.28 was obtained by comparing the individual ESR tooth enamel
      dose estimates with the calculated mean dose for this settlement. The biological
      dosimetry data related to the settlements near SNTS were presented at the
      Workshop. A higher incidence of unstable chromosome aberrations, micronucleus in
      lymphocytes, nuclear abnormalities of thyroid follicular cells, T-cell receptor
      mutations in peripheral blood were found for exposed areas (Dolon', Sarjal) in
      comparison with unexposed ones(Kokpekty). The significant greater frequency of
      stable translocations (results of analyses of chromosome aberrations in
      lymphocytes by the FISH technique) was demonstrated for Dolon' village in
      comparison with Chekoman(unexposed village). The elevated level of stable
      translocations in Dolon' corresponds to a dose of about 180 mSv, which is close
      to the results of ESR dosimetry for this village. The importance of investigating
      specific morphological types of thyroid nodules for thyroid dosimetry studies was
      pointed out. In general the 3rd Dosimetry Workshop has demonstrated remarkable
      progress in developing an international level of common approaches for
      retrospective dose estimations around the SNTS and in understanding the tasks for
      the future joint work in this direction. In the framework of a special session
      the problems of developing a database and registry in order to support
      epidemiological studies around SNTS were discussed. The results of investigation
      of psychological consequences of nuclear tests, which are expressed in the form
      of verbal behaviour, were presented at this session as well.

PMID- 16571925
TI  - 90Sr concentration in cow teeth from South Ural region, Russia, using Monte Carlo
      simulation.
AB  - The Imaging Plate (IP) technique which uses the Monte Carlo code, MCNP, to
      convert IP response to 90Sr concentration with varied thickness of the standard
      source has been proposed in this study. In order to verify the validity of
      simulation calculation in the proposed method, the radial distribution of IP
      signal has been compared between calculation and experiment. The result is, they
      are in good agreement. The proposed method has been applied to a cow tooth from
      the territory contaminated by radioactivity after the accident in the Mayak
      facility in the South Ural, Russia. Two samples have been prepared from the
      tooth, i.e., a thin sample of 1.2+/-0.2 mm in thickness and a thick sample which
      is a half of the tooth. The IP response has been evaluated for the thick sample
      using experimentally made standard sources, and multiplied by a modification
      factor to decide that for the thin sample. The modification factor has been
      determined with MCNP to be 0.83+/-0.08 for a thickness of 1.2+/-0.2 mm. Using
      these values, 90Sr concentration has been estimated to be 0.11 Bq/g for the thin
      sample and 0.12 Bq/g for the thick sample, hence they are in good agreement.

PMID- 16571924
TI  - Radiological situation in the vicinity of Semipalatinsk nuclear test site: Dolon,
      Mostik, Cheremushka and Budene settlements.
AB  - The present situation of radioactive contamination at the village of Dolon and
      nearby villages such as Mostik, Cheremushka and Budene was investigated to serve
      as an aid to resolve dose discrepancy between model calculations and TL
      measurements made for external gamma-ray dose in air in Dolon. The paper was
      focused on the reevaluation of the accumulated levels and distribution of long
      lived radionuclides 137Cs and Pu isotopes in soil using long core samples up to a
      depth of 30 and 100 cm. The inventories of 137Cs and 239,240Pu found were in the
      wide range of 140-10,310 and 140-14,320 Bq/m2, respectively. Most of the Pu in
      soil was tightly incorporated into various sizes of fused particles. Both 137Cs
      and 239,240Pu in soil were accumulated in the smaller soil size fraction of <125
      microm, and the presence of hot particles, probably due to Pu, was clearly
      observed by star-like patterns from alpha-tracks. The obtained data will be
      helpful for evaluating the current and future radiation risks to the people
      living around there.

PMID- 16571926
TI  - External radiation in Dolon village due to local fallout from the first USSR
      atomic bomb test in 1949.
AB  - Dolon village, located about 60 km from the border of the Semipalatinsk Nuclear
      Test Site, is known to be heavily contaminated by local fallout from the first
      USSR atomic bomb test in 1949. External radiation in Dolon was evaluated based on
      recent 137Cs data in soil and calculation of temporal change in the fission
      product composition. After fitting a log-normal distribution to the soil data, a
      137Cs deposition of 32 kBq m-2, which corresponds to the 90th-percentile of the
      distribution, was tentatively chosen as a value to evaluate the radiation
      situation in 1949. Our calculation indicated that more than 95% of the cumulative
      dose for 50 y had been delivered within 1 y after the deposition. The resulting
      cumulative dose for 1 y after the deposition, normalized to the initial
      contamination containing 1 kBq m-2 of 137Cs, was 15.6 mGy, assuming a fallout
      arrival time of 3 h and a medium level of fractionation. Finally, 0.50 Gy of
      absorbed dose in air was derived as our tentative estimate for 1-year cumulative
      external dose in Dolon due to local fallout from the first USSR test in 1949.

PMID- 16571927
TI  - Retrospective dose assessment for the population living in areas of local fallout
      from the Semipalatinsk nuclear test site Part I: External exposure.
AB  - A short analysis of all 111 atmospheric events conducted at the Semipalatinsk
      Test Site (STS) in 1949-1962 with regard to significant off-site exposure (more
      than 5 mSv of the effective dose during the first year after the explosion) has
      been made. The analytical method used to assess external exposure to the
      residents living in settlements near the STS is described. This method makes use
      of the archival data on the radiological conditions, including the measurements
      of exposure rate. Special attention was given to the residents of Dolon and
      Kanonerka villages exposed mainly as a result of the first test, detonated on
      August 29, 1949. For the residents of those settlements born in 1935, the dose
      estimates calculated according to the analytical method, are compared to those
      derived from the thermoluminescence measurements in bricks and electron
      paramagnetic resonance measurements in teeth. The methods described in this paper
      were used for external dose assessment for the cohort members at an initial stage
      of an ongoing epidemiological study conducted by the U.S. National Cancer
      Institute in the Republic of Kazakhstan. Recently revised methods and estimates
      of external exposure for that cohort are given in another paper (Simon et al.) in
      this conference.

PMID- 16571928
TI  - Retrospective dose assessment for the population living in areas of local fallout
      from the Semipalatinsk Nuclear Test Site Part II: Internal exposure to thyroid.
AB  - A methodology to assess internal exposure to thyroid from radioiodines for the
      residents living in settlements located in the vicinity of the Semipalatinsk
      Nuclear Test Site is described that is the result of many years of research,
      primarily at the Moscow Institute of Biophysics. This methodology introduces two
      important concepts. First, the biologically active fraction, is defined as the
      fraction of the total activity on fallout particles with diameter less than 50
      microns. That fraction is retained by vegetation and will ultimately result in
      contamination of dairy products. Second, the relative distance is derived as a
      dimensionless quantity from information on test yield, maximum height of cloud,
      and average wind velocity and describes how the biologically active fraction is
      distributed with distance from the site of the explosion. The parameter is
      derived in such a way that at locations with equal values of relative distance,
      the biologically active fraction will be the same for any test. The estimates of
      internal exposure to thyroid for the residents of Dolon and Kanonerka villages,
      for which the external exposure were assessed and given in a companion paper
      (Gordeev et al. 2006) in this conference, are presented. The main sources of
      uncertainty in the estimates are identified.

PMID- 16571929
TI  - External dose estimates for Dolon village: application of the U.S./Russian joint
      methodology.
AB  - Methods to estimate external dose from radioactive fallout from nuclear tests
      have for many years depended on two types of data: measurements of exposure rate
      in air and an empirically derived power function to describe the change in
      exposure rate with time, Over the last four years, a working group with American
      and Russian participation has developed a bi-national joint methodology that
      offers an improved capability for estimating external dose. In this method,
      external dose is estimated using exposure rate functions derived from data from
      American nuclear tests similar in construction to SNTS (Semipalatinsk Nuclear
      Test Site) devices. For example, in this paper, we derive doses for test #1
      (August 29, 1949) at the SNTS using an exposure rate function for the U.S.
      TRINITY test. For the case of test #1, the average external dose for a person in
      Dolon is estimated to have been about 0.5 Gy compared to 1 to 2 Gy estimated in
      other work. This prediction agrees better with reported EPR measurements in teeth
      from village residents and with measurements of TL signals in bricks from Dolon
      buildings. This report presents the basic elements of the joint methodology model
      for estimation of external dose received from SNTS fallout.

PMID- 16571930
TI  - A gradient of radioactive contamination in Dolon village near the SNTS and
      comparison of computed dose values with instrumental estimates for the 29 August,
      1949 nuclear test.
AB  - Spatial distributions of soil contamination by 137Cs (89 sampling points) and
      239+240Pu (76 points) near and within Dolon village were analyzed. An essential
      exponential decrease of contamination was found in Dolon village: the distance of
      a half reduction in contamination is about 0.87-1.25 km (in a northwest-southeast
      direction from the supposed centerline of the radioactive trace). This fact is in
      agreement with the available exposure rate measurements near Dolon (September
      1949 archive data): on the basis of a few measurements the pattern of the trace
      was estimated to comprise a narrow 2 km corridor of maximum exposure rate. To
      compare computed external doses in air with local dose estimates by retrospective
      luminescence dosimetry (RLD) the gradient of radioactive soil contamination
      within the village was accounted for. The computed dose associated with the
      central axis of the trace was found to be equal to 2260 mGy (calculations based
      on archive exposure rate data). Local doses near the RLD sampling points
      (southeast of the village) were calculated to be in the range 466-780 mGy
      (averaged value: 645+/-70 mGy), which is comparable with RLD data (averaged value
      460+/-92 mGy with range 380-618 mGy). A comparison of the computed mean dose in
      the settlement with dose estimates by ESR tooth enamel dosimetry makes it
      possible to estimate the "upper level" of the "shielding and behavior" factor in
      dose reduction for inhabitants of Dolon village which was found to be 0.28+/
      0.068.

PMID- 16571932
TI  - Unstable-type chromosome aberrations in lymphocytes from individuals living near
      Semipalatinsk nuclear test site.
AB  - The Semipalatinsk nuclear test site area is considered to have been highly
      contaminated with radioactive fallout during 40 years of continuous nuclear
      testing. Individuals living near the nuclear test site are considered to have
      been exposed to both internal and external radiation. In order to assess the
      effects of prolonged radiation, a chromosome analysis was performed in
      lymphocytes from 123 people living in three villages, Dolon, Sarjar and Kaynar,
      and 46 control people in Kokpekty. A micronucleus assay was also conducted in 233
      people in six different contaminated villages and one control village.
      Frequencies of dicentric and ring chromosomes were higher in residents of the
      contaminated area (1.55-2.56 per 1,000 cells) than those of the non-contaminated
      area (0.78 per 1,000 cells). Frequencies of dicentric chromosomes with fragments
      were also higher in the exposed group (0.44-0.96 per 1,000 cells). Among
      residents of the four villages, the incidence of multiple complex chromosome
      aberrations (MCA) was 0.03-0.34%. Incidences of micronucleus were also higher in
      the exposed group (9.36-12.3 per 1,000 lymphocytes) than the non-exposed group
      (7.25 per 1,000 lymphocytes). The higher incidence of unstable-type aberrations
      such as dicentric, ring chromosomes and micronuclei found in residents of
      contaminated areas seems to be mainly caused by internal exposure and other
      factors.

PMID- 16571933
TI  - Biodosimetry study in Dolon and Chekoman villages in the vicinity of
      Semipalatinsk nuclear test site.
AB  - In this paper, the results of a biodosimetry investigation are reported for two
      villages in the area of the Semipalatinsk nuclear testing site: Chekoman and
      Dolon. Chekoman village is considered to be relatively less affected by radiation
      in comparison with Dolon village. The distance between the two villages is about
      100 km and the life styles of the residents are similar. Chromosome aberrations
      in lymphocytes collected from the residents of the two villages were analyzed
      using the fluorescence in situ hybridization technique. Our results showed that
      the average frequency of stable translocations for the Dolon group was
      significantly greater that of the Chekoman group. The elevated level of stable
      translocations with the Dolon residents corresponds to a dose of about 180 mSv.

PMID- 16571931
TI  - International intercomparison of retrospective luminescence dosimetry method:
      sampling and distribution of the brick samples from Dolon' village, Kazakhstan.
AB  - There are still many differences in dose estimates depending on the applied
      methods of retrospective dosimetry in the areas, which were affected by nuclear
      tests at the Semipalatinsk nuclear test site (SNTS). In order to provide more
      correct estimation of radiation doses to population in proximity to the SNTS an
      International Intercomparison of Retrospective Luminescence Dosimetry (RLD)
      method had been proposed. It was suggested there be a comparison of the dose
      estimates for the brick samples from the buildings in the settlement, suffered
      following nuclear tests at the SNTS. With this purpose, during the September
      October 2002 field mission, the team of specialists from Kazakhstan and Japan had
      collected four whole bricks for RLD International Intercomparison. Three
      buildings were selected as sampling locations in Dolon' village (Kazakhstan). The
      slices from these bricks were distributed between six laboratories in Finland,
      Germany, Japan, Russia, UK and USA for independent estimations by the RLD method
      of the accumulated dose of external irradiation. The descriptions of sampling,
      locations, data on geographical coordinates, dates of building construction, mode
      of cutting of samples for distribution, labeling, condition of transportation,
      order of the distribution of samples and information concerning 137Cs and
      239+240Pu soil contamination density in the village and near sampling locations
      are presented in the paper.

PMID- 16571934
TI  - Nuclear abnormalities in aspirated thyroid cells and chromosome aberrations in
      lymphocytes of residents near the Semipalatinsk nuclear test site.
AB  - Chromosomal studies in peripheral lymphocytes from 63 residents near the
      Semipalatinsk nuclear test site, at ages of 52-63 years old, were performed in
      2001-2002. A higher rate of chromosome aberrations was observed in the two
      contaminated villages, Dolon and Sarjal, compared with the control village,
      Kokpekti. Moreover, a relationship of frequency of cells with radiation induced
      chromosome aberrations and the previously estimated exposure dose was observed.
      Furthermore, apparent nuclear abnormalities (ANA) of thyroid follicular cells
      were studied in 30 out of 63 residents, who were examined for chromosome
      aberrations. A higher rate of ANA was also found in the residents in the exposed
      villages compared with those in the control village. These results suggest
      radiation effects both on the chromosomes in peripheral lymphocytes and on the
      follicular cells in the thyroid.

PMID- 16571935
TI  - Increased T-cell receptor mutation frequency in radiation-exposed residents
      living near the Semipalatinsk nuclear test site.
AB  - From 1949 to 1989, 488 nuclear explosions were carried out in Semipalatinsk, and
      the cancer risk is increased in this region. Measuring somatic-cell mutation
      frequencies may be a useful tool for evaluating cancer risk within radiation
      exposed populations. Here, we report the first evidence of increased T-cell
      receptor (TCR) mutations in peripheral blood from radiation-exposed residents of
      Semipalatinsk. The TCR mutation frequency in the highly exposed residents (Dolon
      and Sarzhal) was significantly higher than in the control group (Kokpekti). There
      was no statistically significant difference between the control group and the
      weakly exposed group (Kaynar and Semipalatinsk-city). The TCR mutation assay
      appeared to be a useful biological dosimeter even after a period of 40 years
      since radiation exposure. This may be the result of specific conditions, such as
      the presence of internal exposure.

PMID- 16571936
TI  - Thyroid nodules in the population living around Semipalatinsk nuclear test site:
      possible implications for dose-response relationships study.
AB  - The risk of radiation-induced nodules is higher than the risk for radiation
      induced cancer. Risk factors and specific modifiers of the dose-response
      relationship may vary among different populations and not be well recognized.
      Many thyroid studies have considered thyroid nodularity itself, but not specific
      morphological types of thyroid nodules. There are many specific types of thyroid
      nodules which follow a morphological classification of thyroid lesions, including
      some congenital and tumor-like conditions. Modern equipment and technique can
      help us to identify particular specific types of thyroid nodules. In this study
      we report some results of a clinically applicable approach to materials derived
      from three studies. From 1999 through 2002, we have screened 571 current
      residents from 4 exposed and 1 control village near the Semipalatinsk Nuclear
      Test Site area, who were of similar ages (<20) at the time of major radiation
      fallout events at the SNTS. Prevalent nodules were identified by ultrasound and
      fine-needle aspiration biopsy, cytopathology results. Analysis of ultrasound
      images and cytopathology of thyroid lesions among exposed and non-exposed
      population allowed us to distinguish some interesting ultrasound features for
      specific types of thyroid nodules. We believe that it would be interesting and
      possibly more informative for thyroid dosimetry studies to consider specific
      morphological types of thyroid nodules. We need more detailed research to clarify
      the feasibility of applying these findings for study of the dose-response
      relationship.

PMID- 16571937
TI  - An attempt to develop a database for epidemiological research in Semipalatinsk.
AB  - The present paper reports progress and problems in our development of a database
      for comprehensive epidemiological research in Semipalatinsk whose ultimate aim is
      to examine the effects of low dose radiation exposure on the human body. The
      database was constructed and set up at the Scientific Research Institute of
      Radiation Medicine Ecology in 2003, and the number of data entries into the
      database reached 110,000 on 31 January 2005. However, we face some problems
      concerning size, accuracy and reliability of data which hinder full
      epidemiological analysis. Firstly we need fuller bias free data. The second task
      is to establish a committee for a discussion of the analysis, which should be
      composed of statisticians and epidemiologists, to conduct a research project from
      a long-term perspective, and carry out the collection of data effectively, along
      the lines of the project. Due to the insufficiency of data collected so far, our
      analysis is limited to showing the trends in mortality rates in the high and low
      dose areas.

PMID- 16571938
TI  - Remarkable experiences of the nuclear tests in residents near the Semipalatinsk
      nuclear test site: analysis based on the questionnaire surveys.
AB  - The main objective of this paper is to identify salient experiences of those who
      were exposed to radiation by the nuclear tests at the Semipalatinsk Nuclear Tests
      Site (SNTS). In 2002, our research team of the Research Institute for Radiation
      Biology and Medicine, Hiroshima University, started to conduct some field
      research by means of a questionnaire survey. Through this, we expected to examine
      the health condition of the residents near the SNTS, identify their experiences
      from the nuclear tests, and understand the exposure path. This attempt at
      clarifying the reality of radiation exposure at Semipalatinsk through the use of
      a survey research method is the first of its kind. Among the responses to our
      survey, the present paper focuses mainly upon responses to the questions
      concerning the experiences of the nuclear tests. It deals mainly with direct
      experiences of nuclear tests of the residents characteristic to Semipalatinsk,
      including some new experiences hitherto unnoticed. The present paper touches upon
      their concrete direct experiences of flash, bomb blast, heat, rain and dust. We
      also discuss distinct experiences in Semipalatinsk such as evacuation, through
      the additional use of their testimonies. The data have been compared with the
      results obtained in a similar survey made in Hiroshima and Nagasaki. For the data
      analysis, a statistical method called logistic multiple linear regression
      analysis has been used.

PMID- 16571939
TI  - Human suffering effects of nuclear tests at Semipalatinsk, Kazakhstan:
      established on the basis of questionnaire surveys.
AB  - The main objective of the present paper is to explore the effects of radiation
      exposure on the inhabitants near the Semipalatinsk Nuclear Tests Site (SNTS),
      Kazakhstan. Our research team of the Research Institute for Radiation Biology and
      Medicine, Hiroshima University, started in 2002 to conduct a field research study
      using questionnaire surveys. The present paper attempts to clarify health effects
      and mental problems on the inhabitants by using our questionnaire surveys. Among
      the responses to our survey, the present paper focuses upon responses to the
      questions concerning their health and mental problems. The data in Semipalatinsk
      have been compared with the results obtained in a similar survey conducted by
      Hiroshima and Nagasaki cities. The results show: (1) 33% of the residents replied
      that they felt bad or had very bad health conditions. (2) 70% of the residents
      strongly recognized a causal relationship between their bad health conditions and
      the nuclear tests. (3) The diseases that over 30% of respondents possessed are
      arthralgia/ lower back pain/ arthritis, high-blood pressure, heart disease and
      digestive system disease. (4) Acute radiation injuries from 1949 to 1962 that
      over 20% of respondents experienced were headaches and general malaise. (5)
      Concerning their mental condition, 22% of respondents felt easily frustrated and
      agitated and 21% experienced nightmare.

PMID- 16571940
TI  - Overall image of nuclear tests and their human effects at Semipalatinsk: an
      attempt at analyses based on verbal data.
AB  - The present paper is part of an attempt at finally reconstructing the realities
      of nuclear tests and their human effects near Semipalatinsk, Kazakhstan. As a
      first step, it tries to reconstruct the overall image of nuclear tests and their
      human effects. Our data are 199 written testimonies of those affected by
      radiation, which were collected in 2002 and 2003. We statistically processed
      them, and categorized those words and expressions, which occurred most frequently
      in the testimonies, and obtained some forty categories, which represent the
      experiences, feelings, desires of those affected by radiation. Next, we conducted
      a principal component analysis of the categories. The result shows: (1) The
      experiences of the nuclear tests are arranged along the time axis, with direct
      experiences of the nuclear tests forming one coherent part of the perception and
      memory, and with other subsequent experiences forming another. (2) Of the latter,
      we can discern a core of the experiences on human effects such as "disease,"
      "death," "family," "radiation," and so on. (3) And around this core, we see two
      different trends: one pointing to the current distress and plight, and the other
      pointing to future fear and hope.

PMID- 16571941
TI  - Intercomparison of luminescence measurements of bricks from Dolon' village:
      experimental methodology and results from Japanese laboratory.
AB  - We have applied the thermoluminescence dosimetry technique to measure the total
      external dose from all the nuclear explosions in a few locations near the
      Semipalatinsk nuclear test site in Kazakhstan. The technique was optimized at our
      laboratory by fundamental study of the method of thermoluminescence dosimetry.
      The measured values of each sample at 10 mm depth were 248+/-102 mGy (KSD-1),
      30+/-76 mGy (2(1-3)), 222+/-63 mGy (2(3-2)), 217+/-55 mGy (2(4-1)). The results
      are part of an international intercomparison exercise using bricks collected from
      the areas surrounding the Semipalatinsk nuclear test site.

PMID- 16571942
TI  - Intercomparison of luminescence measurements of bricks from Dolon' village:
      experimental methodology and results of European Study Group.
AB  - Thermoluminescence (TL) and optically stimulated luminescence (OSL) techniques
      were applied to quartz grains extracted from various depths in bricks taken from
      buildings in the village of Dolon', Kazakhstan, to determine the cumulative
      absorbed dose, DT. The measurements were performed in four laboratories (EU
      supported Measurement Group). The results obtained using TL and OSL are compared
      and discussed with reference to known sources of experimental uncertainty and
      relevant luminescence characteristics that may affect the evaluation of the
      absorbed dose. The external nature of the irradiation due to gamma rays from
      artificial radionuclides is verified by the measurement of depth-dose profiles,
      and these are compared with those obtained in previous studies for bricks from
      the same region. To produce these profiles, the cumulative dose due to natural
      background radiation, DBG, was assessed, particularly based on the concentrations
      of radionuclides of lithogenic origin within the bricks and the surrounding
      environment. The consistency of these estimates of DBG was assessed using depth
      dose data and absorbed dose determinations for bricks collected from shielded
      locations. The values of cumulative absorbed dose since the onset of fallout, DX,
      were calculated as the difference between the values of total cumulative dose in
      bricks since its manufacture, DT, and values of DBG. Furthermore, estimations of
      the cumulative absorbed doses in air in the reference location near the sampled
      buildings, RLDX, were obtained using corresponding conversion factors, CRL,
      estimated on the basis of previous work. In addition to results for samples
      distributed for the International Intercomparison, reference is made to relevant
      results from samples that were collected in 1999 from Dolon' village and studied
      as part of EU-supported research.

PMID- 16571943
TI  - Results of EPR dosimetry for population in the vicinity of the most contaminating
      radioactive fallout trace after the first nuclear test in the Semipalatinsk test
      site.
AB  - The method of electron paramagnetic resonance (EPR) spectroscopy for tooth enamel
      is applied to individual radiation dose determination to residents of two
      villages (Dolon and Mostik) in the vicinity of the Semipalatinsk nuclear test
      site in Kazakhstan. These villages are located near the central axis of the
      radioactive fallout trace of the most contaminating surface nuclear test
      conducted in 1949. It is found that excess doses obtained by subtraction of
      natural background dose from dose absorbed in enamel range up to 440 mGy to
      residents of Dolon, whose enamel was formed before 1949, and do not exceed 120
      mGy to younger residents. To residents of Mostik, excess doses do not exceed 100
      mGy regardless of age except for one resident with an extremely high dose of 1.25
      Gy. These results are in agreement with the pattern of radioactive contamination
      of the territory after the nuclear test of 1949 except one case of extremely high
      dose, which should be additionally investigated.

PMID- 16571944
TI  - Radiation dose estimation by tooth enamel EPR dosimetry for residents of Dolon
      and Bodene.
AB  - The method of electron paramagnetic resonance (EPR) dosimetry was applied to the
      enamel of the teeth extracted from the residents of the Dolon and Bodene
      settlements of the Beskaragay district, which is the area adjacent to the
      radioactive fallout of the most contaminating nuclear test of 1949. The
      individual accidental radiation doses due to the fallout were obtained from the
      amplitude of the radiation induced EPR signal from the CO2- radical using the
      calibration method, after determining the parameters of EPR measurements to
      obtain the best reproducibility of the signal intensities. It was shown that
      after subtracting the natural background dose from the total absorbed dose
      obtained by EPR the residents of Dolon and Bodene received accidental radiation
      doses up to 356 mGy with an average value of 74.1+/-45.5 mGy before 1949 while
      the younger population received up to about 100 mGy with an average value of
      11.5+/-37.7 mGy.

PMID- 16571945
TI  - Analysis of current assessments and perspectives of ESR tooth dosimetry for
      radiation dose reconstruction of the population residing near the Semipalatinsk
      nuclear test site.
AB  - Between 1949 and 1989 the Semipalatinsk nuclear test site (SNTS), an area of
      19,000 square km in northeastern Kazakhstan, was the location of over 400 nuclear
      test explosions with a total explosive energy of 6.6 Mt TNT (trinitrotoluene or
      trotyl) equivalent. It is estimated that the bulk of the radiation exposure to
      the population resulted from three tests, conducted in 1949, 1951, and 1953
      although estimations of radiation doses received by the local population have
      varied significantly. Analysis of the published ESR dose reconstruction results
      for residents of the villages near the SNTS show that they do not correlate well
      with other methods of dose assessment (e.g. model dose calculation and thermo
      luminescence dosimetry (TLD) in bricks). The most significant difference in dose
      estimations was found for the population of Dolon, which was exposed as result of
      the first Soviet nuclear test in 1949. Published results of ESR measurements in
      tooth enamel are considerably lower than other dose estimations. Detailed
      analysis of these results is provided and a possible explanation for this
      discrepancy and ways to eliminate it are suggested.

PMID- 16571946
TI  - Considerations regarding the implementation of EPR dosimetry for the population
      in the vicinity of Semipalatinsk nuclear test site based on experience from other
      radiation accidents.
AB  - General aspects of applying the method of retrospective dose estimation by
      electron paramagnetic resonance spectroscopy of human tooth enamel (EPR
      dosimetry) to the population residing in the vicinity of the Semipalatinsk
      nuclear test site are analyzed and summarized. The analysis is based on the
      results obtained during 20 years of investigations conducted in the Medical
      Radiological Research Center regarding the development and practical application
      of this method for wide-scale dosimetrical investigation of populations exposed
      to radiation after the Chernobyl accident and other radiation accidents.

PMID- 16571947
TI  - Toward high sensitivity ESR dosimetry of mammal teeth: the effect of chemical
      treatment.
AB  - Investigations were conducted into chemical treatments suitable for concentrating
      enamel from cow teeth. Cow teeth could be used as alternative to human teeth for
      retrospective dosimetry when human teeth are not available. It is essential to
      remove dentin from tooth enamel for low dose radiation dosimetry in order to
      avoid interference to the ESR signal from organic radicals. Increasing the period
      of chemical treatment with KOH and NaOH reduced the signal intensity of the
      organic radicals. The sensitivity of the dosimetric signal from inorganic
      radicals increased slightly with length of treatment with NaOH, which is
      consistent with removal of dentin, and rose to a maximum of 20% after 5 h with
      KOH (40 degrees C).

PMID- 16571948
TI  - The suitability of FISH chromosome painting and ESR-spectroscopy of tooth enamel
      assays for retrospective dose reconstruction.
AB  - A comparative analysis of two groups of highly irradiated victims was carried out
      in order to evaluate the suitability of two assays for retrospective dose
      assessment: late translocations and electron spin resonance (ESR) dosimetry. The
      first group comprised 24 subjects who exhibited acute radiation syndrome (ARS)
      due to overexposure as a result of nuclear submarine accidents during the period
      1961-1985. Their grades of ARS and individual doses were ascertained by Navy
      physicians who carried out primary examinations and treatment of the exposed
      seamen. Cytogenetic analyses were made 16-40 y after their accidents. During
      medical treatment seven tooth samples were collected for ESR analysis from this
      group. The second group consisted of ten highly irradiated men from the Chernobyl
      accident. Comparison was made between estimates of their average whole-body
      penetrating radiation doses derived from several biological parameters. In three
      cases ESR measurements on tooth enamel from this group were also made.
      Retrospective dosimetry using FISH translocations was attempted 10-13 y later.
      Yields of late translocations were in good agreement with initially estimated
      doses and with doses obtained by ESR spectroscopy analysis of tooth enamel long
      after exposure. It was concluded that both persisting stable translocations and
      ESR spectroscopy signals are suitable with similar efficiencies for retrospective
      biodosimetry after acute whole-body exposure.

PMID- 16571949
TI  - Study on influence of X-ray baggage scan on ESR dosimetry for SNTS using human
      tooth enamel.
AB  - The influence of X-ray baggage scanning on electron spin resonance (ESR)
      dosimetry studies around the Semipalatinsk Nuclear Test Site (SNTS) has been
      examined at Incheon Airport in Korea, which is a transfer point of the routes
      from Kazakhstan to Japan. Utilized dosimeters are Japanese human tooth enamel for
      ESR and glass dosimeters. The difference between the estimated doses with the X
      ray scan and those without it is below the evaluation errors for both ESR and the
      glass dosimeters. For glass dosimeters, the dose from the X-ray scan is estimated
      to be lower than the detection limit for the utilized glass dosimeters of ten
      microGy. This supports the absence of significant difference for the ESR results,
      which have an error in the order of ten mGy. Since ESR dosimetry for SNTS usually
      has similar errors, the dose by the X-ray scan in this study is concluded to be
      negligible in ESR dosimetry using tooth enamel from residents near SNTS.

PMID- 16571950
TI  - Plutonium and uranium in human bones from areas surrounding the Semipalatinsk
      nuclear test site.
AB  - To evaluate the present levels of 239,240Pu and U in residents living near the
      Semipalatinsk nuclear test site, more than 70 bone samples were obtained at
      autopsy. The subjects ranged in age from 30 to 86 years (mean 59.3+/-12.9). Most
      of the samples consisted of victims who died of various diseases. Plutonium and U
      were radiochemically separated and determined by alpha-ray spectrometry. The mean
      concentrations of 239,240Pu and 238U observed were 0.050+/-0.041 mBq/g-ash
      (vertebrae 71, long-bones 18) and 0.28+/-0.13 mBq/g-ash (22.8+/-10.6 microg U/kg
      ash) (vertebrae 58, long bones 16), respectively. The present 239,240Pu levels
      were within the range found for human bone samples from other countries due
      solely to global fallout in the early 1980s. The average U concentration was
      close to the estimate (mean 22.5 microg U/kg-ash) for the UK, and about 10 times
      higher than those estimated for residents in New York City and Japan. By assuming
      that the average concentration of 239,240Pu in bone samples is the value at 45
      years after instantaneous inhalation in 1955, the initial total intake and the
      effective dose for 45 years were estimated as 10 Bq and 0.2 mSv, respectively.
      The annual intake of total U (234,235,238U) and its effective dose for 60 years
      were estimated as 30 Bq for adult and 0.1 mSv, respectively, for chronic
      ingestion.

PMID- 16571951
TI  - An overview on GSF activities at the Semipalatinsk Test Site, Kazakhstan.
AB  - The Semipalatinsk Test Site (STS) in Kazakhstan was one of the major sites used
      by the former USSR for testing nuclear weapons for more than 40 years. Since the
      early 1990s, agricultural activities have been re-established there by
      neighbouring collective and private farms. Therefore, it has become important to
      evaluate the radiological situation and the current and future risk to people
      living on and using the contaminated area. During the last eight years, GSF has
      participated in many international projects performed on the STS to evaluate the
      radiological situation. A large number of soil, vegetation and food samples has
      been collected and analysed. Internal dose is one of the main components of the
      total dose when deriving risk factors for a population living within the test
      site. Internal doses, based on food monitoring and whole body measurements, were
      calculated for adults and were in the range of 13-500 microSv/y due to
      radiocaesium and radiostrontium.

PMID- 16571953
TI  - Changing outcome from aneurysmal subarachnoid hemorrhage: another step closer.

PMID- 16571954
TI  - Sugammadex: a revolutionary approach to neuromuscular antagonism.

PMID- 16571955
TI  - Succinylcholine: new insights into mechanisms of action of an old drug.

PMID- 16571956
TI  - Heart rate variability-guided prophylactic treatment of severe hypotension after
      subarachnoid block for elective cesarean delivery.
AB  - BACKGROUND: Baseline low-to-high frequency ratio (LF/HF) of heart rate
      variability predicted hypotension after subarachnoid block (SAB). LF/HF-guided
      treatment of hypotension with vasopressors or colloids was investigated. METHODS:
      In 80 women scheduled to undergo cesarean delivery during SAB, LF/HF and systolic
      blood pressure (SBP) were analyzed. Patients were randomly assigned to a control
      group (n = 40) or a treatment group (n = 40). Control patients were assigned by
      their baseline LF/HF to one of two subgroups: LF/HF less than 2.5 or LF/HF
      greater than 2.5. Treatment patients with baseline LF/HF greater than 2.5 were
      treated with vasopressor infusion right after SAB (n = 20) or colloid
      prehydration until LF/HF decreased below 2.5 (n = 20). The incidences of
      hypotension (SBP < 80 mmHg) and hypertension (SBP > 140 mmHg) were investigated.
      LF/HF is presented as median and range, and SBP is presented as mean +/- SD.
      RESULTS: Three of 17 control patients with low baseline LF/HF (1.7 [1.3/1.8])
      demonstrated hypotension, and mean SBP remained stable (lowest SBP = 105 +/- 14
      mmHg). In contrast, 20 of 23 control patients with high baseline LF/HF (3.8
      [3.3/4.8]; P < 0.0001 vs. low baseline LF/HF) demonstrated hypotension after SAB:
      lowest SBP = 78 +/- 15 mmHg (P < 0.0001 vs. lowest SBP of control group with low
      baseline LF/HF). LF/HF-guided vasopressor therapy prevented hypotension in 19 of
      20 patients: baseline SBP = 123 +/- 15 mmHg, lowest SBP = 116 +/- 17 mmHg. Mean
      prophylactic colloid infusion of 1,275 +/- 250 ml reduced elevated baseline LF/HF
      from 5.4 (4.1/7.5) to 1.3 (0.8/1.59) (P < 0.0001). Hypotension was prevented in
      17 of 20 patients: baseline SBP = 115 +/- 13 mmHg, lowest SBP = 104 +/- 19 mmHg.
      No hypertensive episode was recognized. CONCLUSIONS: LF/HF may be a tool to guide
      prophylactic therapy of patients at high risk for hypotension after SAB.
      Vasopressor therapy tended to be more effective compared with colloid
      prehydration.

PMID- 16571957
TI  - beta2-adrenoceptor genotype affects vasopressor requirements during spinal
      anesthesia for cesarean delivery.
AB  - BACKGROUND: Maternal hypotension is common after spinal anesthesia for cesarean
      delivery. There is wide variability in the incidence and severity of hypotension
      and in the response to treatment. The beta2 adrenoceptor (beta2AR) possesses
      several polymorphic sites. Codons 16 (Arg16Gly) and 27 (Glu27Gln) have been shown
      to affect desensitization of the receptor. The goal of this study was to
      determine whether genetic variants of the beta2AR alter incidence of hypotension
      or the amount of vasopressor treatment required during spinal anesthesia for
      cesarean delivery. METHODS: One hundred seventy healthy women undergoing elective
      cesarean delivery were studied. Spinal anesthesia was performed with 12 mg
      hyperbaric bupivacaine, 25 microg fentanyl, and 200 microg morphine. Hypotension
      was treated with ephedrine and/or phenylephrine intravenously, and beta2AR
      genotype at codons 16 and 27 was determined. Analysis of variance was used to
      compare variables between genotypes, with data expressed as mean +/- SD. RESULTS:
      Ephedrine or phenylephrine was used in more than 90% of patients, with no
      difference in the incidence of hypotension between beta2AR genotypes. However,
      there was a significant effect of genotype on the amount of vasopressor required.
      Gly16 homozygotes received significantly less ephedrine (18 +/- 14 mg) than Arg16
      homozygotes (28 +/- 13 mg) and Arg16Gly heterozygotes (30 +/- 20 mg; P = 0.0005).
      Glu27 homozygotes required significantly less ephedrine than Gln 27 homozygotes
      (14 +/- 13 vs. 30 +/- 19 mg; P = 0.002). Gln27Glu heterozygotes received less
      ephedrine than Gln27 homozygotes (23 +/- 16 vs. 30 +/- 19 mg; P = 0.03).
      CONCLUSIONS: Glycine at position 16 and/or glutamate at position 27 of the
      beta2AR leads to lower vasopressor use for treatment of hypotension during spinal
      anesthesia.

PMID- 16571958
TI  - Uterine cervical afferents in thoracolumbar dorsal root ganglia express transient
      receptor potential vanilloid type 1 channel and calcitonin gene-related peptide,
      but not P2X3 receptor and somatostatin.
AB  - BACKGROUND: Little is known regarding the phenotype of afferents that innervate
      the uterine cervix. Chronic estrogen sensitizes uterine cervical afferents to
      mechanical distension, but whether this reflects changes in afferent
      neurotransmitter or excitatory ion channel expression is unknown. The authors
      used immunocytochemistry to characterize uterine cervical afferents and the
      effects of estrogen on them. METHODS: Fluorogold was injected into the uterine
      cervix of intact rats (n = 7) and those with ovariectomy alone (n = 9) or with
      estrogen supplementation (n = 8). Bilateral dorsal root ganglia at T12-L2 were
      removed and immunostained for transient receptor potential vanilloid type 1
      (TRPV1), P2X3 receptor, calcitonin gene-related peptide, and somatostatin. The
      proportion of fluorogold-traced dorsal root ganglion neurons expressing each of
      these markers was compared with untraced neurons. RESULTS: Most fluorogold-traced
      cells were found at L1 (> 55%) and were of small diameter (24 microm). TRPV1
      expression was similar between traced and untraced cells, except the estrogen
      treatment increased TRPV1 expression in traced cells. Calcitonin gene-related
      peptide expression was greater in traced than in untraced cells, with no effect
      of experimental treatment. No traced cells expressed the P2X3 receptor or
      somatostatin, although each of these was present in untraced cells. CONCLUSION:
      Uterine cervical afferents in the hypogastric nerve express TRPV1, an important
      nociceptive channel, which may play a role in estrogen-induced sensitization of
      cervical afferents. High expression of calcitonin gene-related peptide suggests a
      sensory and efferent role for this peptide. In contrast to other viscera, these
      afferents do not express somatostatin or P2X3 receptor, indicating a unique
      phenotype of these C fibers.

PMID- 16571959
TI  - Prognosis value of plasma S100B protein levels after subarachnoid aneurysmal
      hemorrhage.
AB  - BACKGROUND: S100B has been described as a biologic marker of neuronal damage. The
      purpose of this study was to assess its prognostic value in patients with
      subarachnoid aneurysmal hemorrhage. METHODS: Seventy-four patients (32 men and 42
      women; age, 48 +/- 11 yr) admitted within 48 h after subarachnoid hemorrhage
      onset and treated by surgical clipping or coiling within 2 days after admission
      were included. World Federation of Neurological Surgeons, Fisher, and Glasgow
      outcome scores at intensive care unit discharge and at 6 months were evaluated.
      Blood concentrations of S100B were determined at admission and daily up to day 8.
      RESULTS: The time course of S100B was increased in patients with high World
      Federation of Neurological Surgeons and Fisher scores. Patients who underwent
      surgical clipping had an S100B time course longer than that of those who
      underwent coiling. This difference remained true after stratification for World
      Federation of Neurological Surgeons and Fisher scores. The threshold of mean
      daily value of S100B predicting a poor outcome at 6 months was 0.4 microg/l
      (sensitivity = 0.50 [95% confidence interval (CI), 0.29-0.71], specificity =
      0.87[corrected] [95% CI, 0.76-0.95]). In multivariate analysis, high World
      Federation of Neurological Surgeons score (odds ratio = 9.5 [95% CI, 3.1-29.4]),
      mean daily S100B value above 0.4 microg/l (odds ratio = 7.3 [95% CI, 2.3-23.6]),
      and age (odds ratio = 1.08 per year [95% CI, 1.01-1.15]) were independent
      predictors of a poor 6-month outcome (Glasgow outcome score 1-3). CONCLUSION:
      Mean daily value of S100B assessed during the first 8 days is a prognostic tool
      complementary to initial clinical evaluation in subarachnoid hemorrhage patients.

PMID- 16571960
TI  - Reversal of rocuronium-induced neuromuscular block by the selective relaxant
      binding agent sugammadex: a dose-finding and safety study.
AB  - BACKGROUND: Sugammadex (Org 25969) forms a complex with steroidal neuromuscular
      blocking agents, thereby reversing neuromuscular block. This study investigated
      the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse
      rocuronium-induced block. METHODS: Twenty-seven male surgical patients aged 18-64
      yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0,
      or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block.
      Anesthesia was induced and maintained using intravenous fentanyl and propofol.
      Neuromuscular function was assessed using acceleromyography. Sugammadex or
      placebo was administered at reappearance of T2 of the train-of-four. The primary
      efficacy variable was the time required for recovery to a train-of-four ratio of
      0.9. RESULTS: Sugammadex decreased median recovery time in a dose-dependent
      manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0
      mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium
      induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was
      excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex
      increased the proportion of the rocuronium dose excreted unchanged in the urine
      (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within
      16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was
      observed in any patient. CONCLUSION: At doses of 2.0 mg/kg or greater, sugammadex
      safely reversed 0.6 mg/kg rocuronium-induced neuromuscular block in a dose
      dependent manner. Sugammadex enhanced renal excretion of rocuronium and was
      excreted unchanged by the kidneys.

PMID- 16571961
TI  - Atlantoaxial subluxation in different intraoperative head positions in patients
      with rheumatoid arthritis.
AB  - BACKGROUND: Disorders of the cervical spine are often observed in patients with
      rheumatoid arthritis (RA). However, the best head position for RA patients with
      atlantoaxial subluxation in the perioperative period is unknown. This study
      investigated head position during general anesthesia for the patients with RA and
      proven atlantoaxial subluxation. METHODS: During anesthesia of patients with RA
      and proven atlantoaxial subluxation, the authors used fluoroscopy to obtain a
      lateral view of the upper cervical spine in four different positions: the mask
      position, the intubation position, the flat pillow position, and the protrusion
      position. Copies of the still fluoroscopic images were used to determine the
      anterior atlantodental interval, the posterior atlantodental interval, and the
      angle of atlas and axis (C1-C2 angle). RESULTS: The anterior atlantodental
      interval was significantly smaller in the protrusion position (2.3 mm) than in
      the flat pillow position (5.1 mm) (P < 0.05). The posterior atlantodental
      interval was significantly greater in the protrusion position (18.9 mm) than in
      the flat pillow position (16.2 mm) (P < 0.05). The C1-C2 angle was, on average,
      9.3 degrees greater in the protrusion position than in the flat pillow position
      (P < 0.05). CONCLUSION: This study showed that the protrusion position using a
      flat pillow and a donut-shaped pillow during general anesthesia reduced the
      anterior atlantodental interval and increased the posterior atlantodental
      interval in RA patients with atlantoaxial subluxation. This suggests that the
      protrusion position, which involves support of the upper cervical spine and
      extension at the craniocervical junction, might be advantageous for these
      patients.

PMID- 16571962
TI  - Preoperative evaluation of extension capacity of the occipitoatlantoaxial complex
      in patients with rheumatoid arthritis: comparison between the Bellhouse test and
      a new method, hyomental distance ratio.
AB  - BACKGROUND: The authors devised a new method, the hyomental distance ratio
      (HMDR), for preoperatively identifying patients with a reduced
      occipitoatlantoaxial extension capacity, which was defined as the ratio of the
      hyomental distance in head extension position to that in the neutral position.
      They compared the accuracy of the HMDR with that of the Bellhouse test in 40
      patients with rheumatoid arthritis. METHODS: Each patient wearing goggles on
      which a goniometer was mounted sat upright with the head in the neutral position
      and then extended the head maximally. The angle of the goggles and the hyomental
      distance were measured in the two head positions, and a lateral cervical
      radiograph was taken simultaneously. The Bellhouse angle was defined as a
      difference in the angles of the goggles between these positions. RESULTS: Median
      values of the radiologic occipitoatlantoaxial extension angle and the Bellhouse
      angle were 11.2 degrees and 24.9 degrees , respectively. In 21 of 40 patients,
      the radiologic occipitoatlantoaxial extension angle was less than 12 degrees
      (reduced occipitoatlantoaxial extension capacity). In these patients, extension
      of the median angle of 16.4 degrees occurred at the subaxial regions and was
      greater than that of 8.5 degrees in patients with a radiologic
      occipitoatlantoaxial extension angle of 12 degrees or more (P < 0.01). As a
      result, a strong relation between the Bellhouse angle and radiologic
      occipitoatlantoaxial extension angle was not established (P < 0.01, r = 0.48). In
      contrast, the HMDR correlated well with the radiologic occipitoatlantoaxial
      extension angle (P < 0.0001, r = 0.88). The areas under the receiver operating
      characteristic curve of the Bellhouse test and the HMDR were 0.72 and 0.95,
      respectively. CONCLUSIONS: The HMDR was a good predictor of a reduced
      occipitoatlantoaxial extension capacity in patients with rheumatoid arthritis,
      but the Bellhouse test was not a clinically reliable method.

PMID- 16571963
TI  - Titration of propofol for anesthetic induction and maintenance guided by the
      bispectral index: closed-loop versus manual control: a prospective, randomized,
      multicenter study.
AB  - BACKGROUND: This report describes a closed-loop titration of propofol target
      control infusion based on a proportional-differential algorithm guided by the
      Bispectral Index (BIS) allowing induction and maintenance of general anesthesia
      and compares this to manual propofol target control infusion. METHODS: One
      hundred sixty-four patients scheduled to undergo elective minor or major surgery
      were prospectively randomized in a multicenter study into the closed-loop (n =
      83) or manual target control infusion group (n = 81). The goal was to reach a BIS
      target of 50 during induction and to maintain it between 40 and 60 during
      maintenance. For both groups, remifentanil target control infusion was adjusted
      manually, and ventilation was without nitrous oxide. RESULTS: Closed-loop control
      was able to provide anesthesia induction and maintenance for all patients. During
      induction, propofol consumption was lower in the closed-loop group (1.4 +/- 0.5
      vs. 1.8 +/- 0.6 mg/kg; P < 0.0001), but the duration was longer (320 +/- 125 vs.
      271 +/- 120 s; P < 0.0002). Adequate anesthesia maintenance, defined as the BIS
      in the range of 40-60, was significantly higher in the closed-loop group (89 +/-
      9 vs. 70 +/- 21%; P < 0.0001), with a decrease of the occurrence of BIS less than
      40 (8 +/- 8 vs. 26 +/- 22%; P < 0.0001). Time from discontinuation of propofol
      infusion to tracheal extubation was shorter in the closed-loop group (7 +/- 4 vs.
      10 +/- 7 min; P < 0.017). Unwanted somatic events and hemodynamic instability
      were similar. CONCLUSION: Automatic control of consciousness using the BIS is
      clinically feasible and outperforms manual control.

PMID- 16571964
TI  - A new equal area method to calculate and represent physiologic, anatomical, and
      alveolar dead spaces.
AB  - BACKGROUND: Physiologic dead space is usually estimated by the Bohr-Enghoff
      equation or the Fletcher method. Alveolar dead space is calculated as the
      difference between anatomical dead space estimated by the Fowler equal area
      method and physiologic dead space. This study introduces a graphical method that
      uses similar principles for measuring and displaying anatomical, physiologic, and
      alveolar dead spaces. METHODS: A new graphical equal area method for estimating
      physiologic dead space is derived. Physiologic dead spaces of 1,200 carbon
      dioxide expirograms obtained from 10 ventilated patients were calculated by the
      Bohr-Enghoff equation, the Fletcher area method, and the new graphical equal area
      method and were compared by Bland-Altman analysis. Dead space was varied by
      varying tidal volume, end-expiratory pressure, inspiratory-to-expiratory ratio,
      and inspiratory hold in each patient. RESULTS: The new graphical equal area
      method for calculating physiologic dead space is shown analytically to be
      identical to the Bohr-Enghoff calculation. The mean difference (limits of
      agreement) between the physiologic dead spaces calculated by the new equal area
      method and Bohr-Enghoff equation was -0.07 ml (-1.27 to 1.13 ml). The mean
      difference between new equal area method and the Fletcher area method was -0.09
      ml (-1.52 to 1.34 ml). CONCLUSIONS: The authors' equal area method for
      calculating, displaying, and visualizing physiologic dead space is easy to
      understand and yields the same results as the classic Bohr-Enghoff equation and
      Fletcher area method. All three dead spaces--physiologic, anatomical, and
      alveolar--together with their relations to expired volume, can be displayed
      conveniently on the x-axis of a carbon dioxide expirogram.

PMID- 16571965
TI  - An evaluation of transcutaneous carbon dioxide partial pressure monitoring during
      apnea testing in brain-dead patients.
AB  - BACKGROUND: Diagnosis of brain death usually requires an arterial carbon dioxide
      partial pressure (Paco2) of 60 mmHg during the apnea test, but the increase in
      Paco2 is unpredictable. The authors evaluated whether transcutaneous carbon
      dioxide partial pressure (Ptcco2) monitoring during apnea test can predict that a
      Paco2 of 60 mmHg has been reached. METHODS: The authors compared Ptcco2 measured
      with a transcutaneous ear sensor (V-Sign Sensor, Sentec Digital Monitoring
      System; SENTEC-AG, Therwil, Switzerland) and Paco2 obtained from arterial blood
      gas measurements in 32 clinically brain-dead patients. RESULTS: In the first 20
      patients, the mean Paco2-Ptcco2 gradient was 0.7 +/- 3.6 mmHg at baseline and 8.7
      +/- 7.1 mmHg after 20 min of apnea. Using receiver operating characteristic curve
      analysis (area under the curve: 0.983 +/- 0.013), the best threshold value of
      Ptcco2 to predict that a Paco2 of 60 mmHg had been reached was 60 mmHg (positive
      predictive value: 1.00 [0.93-1.00]). In the following 12 patients investigated
      with use of this Ptcco2 target value of 60 mmHg, the mean duration of the apnea
      test (11 +/- 4 vs. 20 +/- 0 min; P < 0.001), hypercapnia (74.0 +/- 4.9 vs. 98.3
      +/- 20.0 mmHg; P < 0.001), acidosis (pH: 7.18 +/- 0.06 vs. 7.11 +/- 0.08; P <
      0.001), and decrease in arterial oxygen partial pressure (-47 +/- 44 vs. -95 +/-
      89; P < 0.05) at the end of the test were reduced as compared with the 20-min
      apnea test group. CONCLUSION: During the apnea test in brain-dead patients, a
      Ptcco2 of 60 mmHg accurately predicts that a Paco2 of 60 mmHg has been reached.
      This may allow a reduction in the duration of the apnea test and consecutively
      limit occurrence of complications.

PMID- 16571966
TI  - Spectral entropy as a measure of hypnosis in children.
AB  - BACKGROUND: The Datex-Ohmeda S/5 Entropy Module (Datex-Ohmeda Division,
      Instrumentarium Corp., Helsinki, Finland), using time-frequency balanced Spectral
      Entropy, is a novel tool for monitoring the hypnotic state during anesthesia. The
      Entropy Module produces two values, State Entropy (SE) and Response Entropy (RE),
      and in adults, it has been shown to measure reliably the hypnotic effects of
      various drugs. In children, Spectral Entropy has been only preliminary studied.
      The authors' aim was to study Spectral Entropy as a marker of hypnotic state
      during general anesthesia in infants and children. METHODS: Twenty infants (aged
      1 month-1 yr) and 40 children (aged 1-15 yr) were anesthetized for surgery using
      standardized sevoflurane-nitrous oxide-based anesthesia. The relationships
      between SE, RE, or Bispectral Index (BIS) and (1) a modified Observer's
      Assessment of Alertness/Sedation Scale, (2) non-steady state end-tidal
      concentration of sevoflurane, (3) steady state end-tidal concentration of
      sevoflurane, and (4) hemodynamic values were calculated using prediction
      probability, nonlinear regression, and correlation coefficients, as appropriate.
      The performances of SE, RE, and BIS were compared. RESULTS: The prediction
      probability values (+/- SEM) of SE, RE, and BIS versus the modified Observer's
      Assessment of Alertness/Sedation Scale in the induction phase were 0.83 +/- 0.06,
      0.88 +/- 0.06, and 0.87 +/- 0.08 for children and 0.76 +/- 0.08,0.79 +/- 0.08,
      and 0.73 +/- 0.10 for infants; values in the emergence phase were 0.68 +/- 0.05,
      0.74 +/- 0.04, and 0.64 +/- 0.05 for children and 0.64 +/- 0.07, 0.69 +/- 0.06,
      and 0.72 +/- 0.06 for infants, respectively. SE, RE, and BIS values were
      inversely proportionally related to the end-tidal concentration of sevoflurane
      for children, but for infants, the correlation was much less clear. No
      significant correlations were found between SE, RE, or BIS values and the
      hemodynamic values. CONCLUSIONS: Spectral Entropy may be a useful tool for
      measuring the level of hypnosis in anesthetized children and seems to perform as
      well as BIS. In infants, the clinical usefulness of both these
      electroencephalogram-derived methods must be evaluated in further controlled
      studies.

PMID- 16571967
TI  - Reversal of profound rocuronium neuromuscular blockade by sugammadex in
      anesthetized rhesus monkeys.
AB  - BACKGROUND: Reversal of neuromuscular blockade can be accomplished by chemical
      encapsulation of rocuronium by sugammadex, a synthetic gamma-cyclodextrin
      derivative. The current study determined the feasibility of reversal of
      rocuronium-induced profound neuromuscular blockade with sugammadex in the
      anesthetized rhesus monkey using train-of-four stimulation. METHODS: Four female
      rhesus monkeys each underwent three experiments. In each experiment, first, a 100
      microg/kg dose of rocuronium was injected and spontaneous recovery was monitored.
      After full recovery, a 500-microg/kg dose of rocuronium was injected. Up to this
      point, all three experiments in a single monkey were identical. One minute after
      this rocuronium injection, either one of the two tested dosages of sugammadex
      (1.0 or 2.5 mg/kg) was injected or saline was injected. RESULTS: Injection of 100
      microg/kg rocuronium resulted in a mean neuromuscular blockade of 93.0% (SD =
      4%), and profound blockade was achieved by injection of 500 microg/kg. In all
      experiments, a 100% neuromuscular blockade was achieved at this dose. After
      injection of the high rocuronium dose, the 90% recovery of the train-of-four
      ratio took 28 min (SD = 7 min) after saline, 26 min (SD = 9.5 min) after 1 mg/kg
      sugammadex, and 8 min (SD = 3.6 min) after 2.5 mg/kg sugammadex. Signs of
      residual blockade or recurarization were not observed. Injection of sugammadex
      had no significant effects on blood pressure or heart rate. CONCLUSIONS: Chemical
      encapsulation of rocuronium by sugammadex is a new therapeutic mechanism allowing
      effective and rapid reversal of profound neuromuscular blockade induced by
      rocuronium in anesthetized rhesus monkeys.

PMID- 16571968
TI  - Activation and inhibition of human muscular and neuronal nicotinic acetylcholine
      receptors by succinylcholine.
AB  - BACKGROUND: Succinylcholine is one of the most widely used muscle relaxants in
      clinical anesthesia and emergency medicine. Although the clinical advantages and
      cardiovascular side effects are well known, its mechanism of action within the
      human nicotinic cholinergic receptor system remains to be understood. The aim of
      this study was to investigate the effect of succinylcholine on human muscle and
      neuronal nicotinic acetylcholine receptor (nAChR) subtypes. METHODS: Xenopus
      laevis oocytes were injected with human messenger RNA for muscle and neuronal
      nAChR subunits. Receptor activation, desensitization, and inhibition induced by
      the natural ligand acetylcholine or by succinylcholine was studied using a
      multichannel two-electrode voltage clamp setup. Responses were measured as peak
      current and net charge. RESULTS: Succinylcholine concentration-dependently
      activated the muscle-type nAChR with an EC50 value of 10.8 microm (95% confidence
      interval, 9.8-11.9 microm), and after the initial activation, succinylcholine
      desensitized the muscle-type nAChR. Succinylcholine did not activate the neuronal
      nAChR subtypes alpha3beta2, alpha3beta4, alpha4beta2, or alpha7 at concentrations
      up to 1 mm and was a poor inhibitor at these receptor subtypes, with IC50 values
      above 100 microm. CONCLUSION: Succinylcholine activates the muscle-type nAChR
      followed by desensitization. The observation that succinylcholine does not
      inhibit the presynaptic alpha3beta2 autoreceptor at clinically relevant
      concentrations provides a possible mechanistic explanation for the typical lack
      of tetanic fade in succinylcholine-induced neuromuscular blockade. Finally,
      cardiovascular side effects (e.g., tachyarrhythmias) of succinylcholine are not
      mediated via direct activation of the autonomic ganglionic alpha3beta4 subtype
      because succinylcholine does not activate the neuronal nAChRs.

PMID- 16571969
TI  - Comparison of arginine vasopressin, terlipressin, or epinephrine to correct
      hypotension in a model of anaphylactic shock in anesthetized brown Norway rats.
AB  - BACKGROUND: Arginine vasopressin (AVP) and terlipressin were proposed as
      alternatives to catecholamines in shock states characterized by decreased plasma
      AVP concentrations. The endogenous plasma AVP profile in anaphylactic shock is
      unknown. In an ovalbumin-sensitized anesthetized anaphylactic shock rat model,
      the authors investigated (1) plasma AVP concentrations and (2) the dose versus
      mean arterial pressure response for exogenous AVP and terlipressin and compared
      them with those of epinephrine. METHODS: In a first series of rats (n = 12),
      endogenous plasma AVP concentrations were compared with a model of
      pharmacologically induced hypotension (nicardipine, n = 12). A second series was
      randomly assigned to three groups (AVP, n = 7; terlipressin, n = 7; epinephrine,
      n = 7) and dose (AVP: 8 doses, 0.03-100 U/kg; terlipressin: 7 doses, 0.03-30
      microg/kg; epinephrine: 7 doses, 0.3-300 microg/kg)-response mean arterial
      pressure curves were plotted. Data are expressed as mean +/- SD. RESULTS:
      Endogenous plasma AVP concentrations were significantly lower in anaphylactic
      shock (57 +/- 26 pg/ml) than in the nicardipine group (91 +/- 43 pg/ml; P <
      0.05). The ED50 was 10.6 microg/kg (95% confidence interval, 7.1-15.9) for
      epinephrine and 4.1 U/kg (95% confidence interval, 3.0-5.6) for AVP. Terlipressin
      did not change mean arterial pressure, regardless of the dose used. CONCLUSIONS:
      In a rat model, anaphylactic shock is associated with inadequately low plasma AVP
      concentrations. For clinically relevant doses, AVP and epinephrine had comparable
      effects on mean arterial pressure and heart rate values, whereas, unexpectedly,
      terlipressin was ineffective. These results are consistent with reports in humans
      experiencing anaphylaxis where AVP injection restored arterial pressure.

PMID- 16571970
TI  - The well-being model: a new drug interaction model for positive and negative
      effects.
AB  - BACKGROUND: Drugs are routinely combined in anesthesia and pain management to
      obtain an enhancement of the desired effects. However, a parallel enhancement of
      the undesired effects might take place as well, resulting in a limited
      therapeutic usefulness. Therefore, when addressing the question of optimal drug
      combinations, side effects must be taken into account. METHODS: By extension of a
      previously published interaction model, the authors propose a method to study
      drug interactions considering also their side effects. A general outcome
      parameter identified as patient's well-being is defined by superposition of
      positive and negative effects. Well-being response surfaces are computed and
      analyzed for varying drugs pharmacodynamics and interaction types. In particular,
      the existence of multiple maxima and of optimal drug combinations is investigated
      for the combination of two drugs. RESULTS: Both drug pharmacodynamics and
      interaction type affect the well-being surface and the deriving optimal
      combinations. The effect of the interaction parameters can be explained in terms
      of synergy and antagonism and remains unchanged for varying pharmacodynamics. For
      all simulations performed for the combination of two drugs, the presence of more
      than one maximum was never observed. CONCLUSIONS: The model is consistent with
      clinical knowledge and supports previously published experimental results on
      optimal drug combinations. This new framework improves understanding of the
      characteristics of drug combinations used in clinical practice and can be used in
      clinical research to identify optimal drug dosing.

PMID- 16571971
TI  - Halothane does not inhibit the functional coupling between the beta2-adrenergic
      receptor and the Galphas heterotrimeric G protein.
AB  - BACKGROUND: This study investigated whether halothane affects the functional
      coupling between the beta2 adrenergic receptor and the alpha subunit of its
      cognate stimulatory heterotrimeric guanosine-5'-triphosphate (GTP)-binding
      protein (Galphas). The authors hypothesized that halothane does not affect
      isoproterenol-promoted guanosine nucleotide exchange at Galphas and hence would
      not affect isoproterenol-induced relaxation of airway smooth muscle. METHODS:
      Halothane effects on isoproterenol-induced inhibition of calcium sensitivity were
      measured in permeabilized porcine airway smooth muscle. Galphas nucleotide
      exchange was measured in crude membranes prepared from COS-7 cells transfected to
      transiently coexpress the human beta1 or beta2 receptor each with human short
      Galphas. A radioactive, nonhydrolyzable analog of GTP, [S]GTPgammaS, was used as
      the reporter for nucleotide exchange at Galphas. RESULTS: Halothane (0.75 mm,
      approximately 2.8 minimum alveolar concentration [MAC] in pigs) did not affect
      isoproterenol-induced inhibition of calcium sensitivity. Isoproterenol caused a
      time- and concentration-dependent increase in Galphas nucleotide exchange.
      Halothane, even at concentrations of 1.5 mm (approximately 5.6 MAC), had no
      effect on basal Galphas nucleotide exchange in the absence of isoproterenol,
      whereas halothane inhibited isoproterenol-promoted Galphas nucleotide exchange in
      both the beta1-Galphas and beta2-Galphas expressing membranes. However, the
      effect was significantly greater on beta1-Galphas coupling compared with beta2
      Galphas coupling, with no effect on beta2-Galphas coupling at 2.8 MAC halothane.
      CONCLUSION: Halothane does not inhibit the biochemical coupling between the beta2
      receptor and Galphas and hence does not affect the inhibition of calcium
      sensitivity induced by isoproterenol. Therefore, halothane should not affect the
      efficacy of beta2 agonists, as suggested by studies of in vivo animal models of
      asthma.

PMID- 16571972
TI  - Propofol inhibits phosphorylation of N-methyl-D-aspartate receptor NR1 subunits
      in neurons.
AB  - BACKGROUND: Anesthetics may interact with ionotropic glutamate receptors to
      produce some of their biologic actions. Cellular studies reveal that the
      ionotropic glutamate receptors, N-methyl-D-aspartate receptors (NMDARs), can be
      phosphorylated on their NR1 subunits at the C-terminal serine residues, which is
      a major mechanism for the regulation of NMDAR functions. It is currently unknown
      whether anesthetics have any modulatory effects on NMDAR NR1 subunit
      phosphorylation. METHODS: The possible effect of a general anesthetic propofol on
      phosphorylation of NR1 subunits at serine 897 (pNR1S897) and 896 (pNR1S896) was
      detected in cultured rat cortical neurons. RESULTS: Propofol consistently reduced
      basal levels of pNR1S897 and pNR1S896 in a concentration-dependent manner. This
      reduction was rapid as the reliable reduction of pNR1S896 developed 1 min after
      propofol administration. Pretreatment of cultures with the protein phosphatase 2A
      inhibitors okadaic acid or calyculin A blocked the effect of propofol on the NR1
      phosphorylation, whereas okadaic acid or calyculin A alone did not alter basal
      pNR1S897 and pNR1S896 levels. In addition, propofol decreased tyrosine
      phosphorylation of protein phosphatase 2A at tyrosine 307, resulting in an
      increase in protein phosphatase 2A activity. In the presence of propofol, the
      NMDAR agonist-induced intracellular Ca2+ increase was impaired in neurons with
      dephosphorylated NR1 subunits. CONCLUSIONS: Together, these data indicate an
      inhibitory effect of a general anesthetic propofol on NMDAR NR1 subunit
      phosphorylation in neurons. This inhibition was mediated through a signaling
      mechanism involving activation of protein phosphatase 2A.

PMID- 16571973
TI  - Xenon impairs neurocognitive and histologic outcome after cardiopulmonary bypass
      combined with cerebral air embolism in rats.
AB  - BACKGROUND: The neuroprotective properties of xenon may improve cerebral outcome
      after cardiac surgery using cardiopulmonary bypass (CPB). However, its
      disposition to expand gaseous bubbles that during CPB present as cerebral air
      emboli (CAE) could abolish any beneficial effect or even worsen cerebral outcome.
      Therefore, the authors studied the impact of xenon on neurologic, cognitive, and
      histologic outcome after CPB combined with CAE in rats. METHODS: With
      institutional review board approval, 40 rats were assigned to four groups (n =
      10). In two CPB-CAE groups, rats were subjected to 90 min of normothermic CPB
      with 10 repetitively administered CAEs (0.3 microl/bolus). Rats in two sham
      groups were not exposed to CPB and CAE. Groups were further subdivided into xenon
      (56%; 20 min before, during, and 30 min after CPB) and nitrogen groups.
      Neurologic and cognitive function was tested until postoperative day 14, when
      cerebral infarct volumes were determined. RESULTS: Animals of the CPB-CAE groups
      showed transient deficits in gross neurologic function. Further, rats of the CPB
      CAE-xenon group demonstrated impaired fine motor and cognitive performance
      persisting until postoperative day 14. Consistently, infarct volumes were larger
      in the CPB-CAE-xenon group compared with the CPB-CAE-nitrogen group (P = 0.03).
      CONCLUSIONS: This is the first demonstration in which the neurologic effects of
      CAE have been examined in a rat model of CPB. Xenon exposure aggravated the
      neurologic dysfunction that is produced by CAE during CPB; potential
      neuroprotective effects of xenon may have been masked by the effects of xenon on
      CAE.

PMID- 16571974
TI  - Isoflurane, but not sevoflurane, increases transendothelial albumin permeability
      in the isolated rat lung: role for enhanced phosphorylation of caveolin-1.
AB  - BACKGROUND: Caveolae mediated transendothelial transport of albumin has recently
      been shown to be the primary mechanism regulating microvascular endothelial
      albumin permeability. The authors investigated the effects of isoflurane and
      sevoflurane on pulmonary endothelial albumin permeability and assessed the
      potential role of the caveolae scaffold protein, caveolin-1, in these effects.
      METHODS: Isolated rat lungs and cultured rat lung microvessel endothelial cells
      (RLMVECs) were exposed to 1.0 or 2.0 minimum alveolar concentration (MAC)
      isoflurane or sevoflurane for 30 min. I-albumin permeability-surface area product
      and capillary filtration coefficient were determined in the isolated lungs. In
      RLMVECs, uptake and transendothelial transport of I-albumin were measured in the
      absence and presence of pretreatment with 2 mm methyl-beta-cyclodextrin, a
      caveolae-disrupting agent. Uptake of fluorescent-labeled albumin, as well as
      phosphorylation of Src kinase and caveolin-1, was also determined. In Y14F
      caveolin-1 mutant (nonphosphorylatable) expressing RLMVECs, uptake of I-albumin
      and phosphorylation of caveolin-1 were evaluated. RESULTS: In the isolated lungs,
      2.0 MAC isoflurane increased I-albumin permeability-surface area product by 48%
      without affecting capillary filtration coefficient. In RLMVECs, isoflurane more
      than doubled the uptake of I-albumin and caused a 54% increase in the
      transendothelial transport of I-albumin. These effects were blocked by
      pretreatment with methyl-beta-cyclodextrin. The isoflurane-induced increase in
      uptake of I-albumin in wild-type RLMVECs was abolished in the Y14F-caveolin-1
      mutant expressing cells. Isoflurane also caused a twofold increase in Src and
      caveolin-1 phosphorylation. Neither 1.0 MAC isoflurane nor 1.0 or 2.0 MAC
      sevoflurane affected any index of albumin transport or phosphorylation of
      caveolin-1. CONCLUSION: Isoflurane, but not sevoflurane, increased lung
      transendothelial albumin permeability through enhancement of caveolae-mediated
      albumin uptake and transport in the isolated lung. This effect may involve an
      enhanced phosphorylation of caveolin-1.

PMID- 16571975
TI  - Discontinuous monitoring of propofol concentrations in expired alveolar gas and
      in arterial and venous plasma during artificial ventilation.
AB  - BACKGROUND: Analyzing propofol concentration in expired alveolar gas (cPA) may be
      considered as a convenient, noninvasive method to follow the propofol
      concentration in plasma (cPPL). In the current study, the authors established
      procedures to measure cPA and cPPL for the assessment of their relation in two
      animal models during anesthesia. METHODS: Expired alveolar gas and mixed venous
      and arterial blood were simultaneously sampled during continuous application of
      propofol for general anesthesia to three goats and three pigs. Propofol infusion
      rates were varied to modify plasma concentrations. cPA, sampled cumulatively over
      several respiratory cycles, was quantified by thermal desorption gas
      chromatography-mass spectrometry. cPPL was determined using reversed phase high
      performance liquid chromatography with fluorescence detection. RESULTS: cPA
      ranged from 0 to 1.4 and from 0 to 22 parts per billion in goats and pigs,
      respectively, at cPPL of 0-8 microg/ml. The relation between cPA and cPPL was
      linear; however, the slopes of the regression lines varied between animals.
      CONCLUSION: Propofol can be quantified in expired alveolar gas. The results
      stress the role of marked species-specific variability.

PMID- 16571976
TI  - Intravenous anesthetics inhibit capacitative calcium entry in pulmonary venous
      smooth muscle cells.
AB  - BACKGROUND: The authors have previously demonstrated that propofol attenuates
      capacitative calcium entry (CCE) via the protein kinase C signaling pathway in
      pulmonary artery smooth muscle cells (PVSMCs). The current goals were to
      determine whether CCE exists in PVSMCs; to assess the roles of the protein kinase
      C, tyrosine kinase (TK), and rho-kinase signaling pathways in regulating CCE; and
      to investigate the extent and cellular mechanisms by which intravenous
      anesthetics (thiopental, midazolam, ketamine, and propofol) alter CCE. METHODS:
      Primary cultures of fura-2-loaded canine PVSMCs were placed in a dish (37 degrees
      C) on an inverted fluorescence microscope. Intracellular Ca2+ concentration
      ([Ca2+]i) was measured as the 340/380 fluorescence ratio in individual PVSMCs.
      Thapsigargin, a sarcoplasmic reticulum Ca2+-adenosine triphosphatase inhibitor,
      was used to deplete intracellular Ca2+ stores after removing extracellular Ca2+.
      CCE was then activated by restoring extracellular Ca2+ (2.2 mm). RESULTS:
      Thapsigargin caused a transient increase in [Ca2+]i (160 +/- 6%). Restoring
      extracellular Ca2+ caused a rapid peak increase in [Ca2+]i (155 +/- 7% of
      baseline), followed by a sustained increase in [Ca2+]i (129 +/- 5% of baseline),
      i.e., CCE was stimulated in PVSMCs. Neither protein kinase C activation nor
      inhibition had an effect on CCE. rho-Kinase inhibition also had no effect on CCE,
      whereas TK inhibition attenuated both peak and sustained CCE. Thiopental,
      midazolam, ketamine, and propofol each attenuated both peak and sustained CCE. TK
      inhibition abolished the thiopental-, midazolam-, and ketamine-induced, but not
      the propofol-induced, decreases in CCE. CONCLUSION: Capacitative calcium entry is
      present in canine PVSMCs. Thiopental, midazolam, and ketamine attenuate CCE
      primarily via the TK signaling pathway. Propofol attenuates CCE via a TK
      independent mechanism.

PMID- 16571977
TI  - Propofol increases presynaptic inhibition of ia afferents in the intact human
      spinal cord.
AB  - BACKGROUND: In vitro studies indicate that the primary molecular targets of
      propofol in the spinal cord are gamma-aminobutyric acid (GABA) type A receptors.
      Because of the complexity of the central nervous system, specific GABA-mediated
      effects have not yet been isolated in humans. Here, the authors used heteronymous
      Ia facilitation of the soleus H-reflex from the femoral nerve as a specific
      pathway involving GABA to demonstrate a presynaptic GABA-mediated effect of
      propofol in humans. METHODS: The study was performed in 10 volunteers aged 23-32
      yr. The soleus H-reflex was evoked by stimulation of the tibial nerve in the
      popliteal fossa. The stimulation current was adjusted to yield an unconditioned H
      reflex of 15% of the maximal muscle response to electric stimulation of the
      tibial nerve. The soleus H-reflex was conditioned by stimulating Ia afferents
      from the quadriceps femoris in the femoral triangle. The stimulus was applied 0.3
      0.4 ms after the onset of facilitation, to assure a purely monosynaptic
      excitatory postsynaptic potential from quadriceps Ia afferents to the soleus
      motoneuron. At least 45 conditioned (femoral and tibial) and unconditioned (only
      tibial) stimuli were applied in random order. The authors compared the amount of
      heteronymous H-reflex facilitation under a concentration of 2 microg/ml propofol
      with control values obtained before and after the propofol infusion. RESULTS: H
      reflex facilitation due to the conditioning stimulus during propofol
      administration was significantly (P < 0.05, t test) decreased by an average of
      43% in all patients in comparison with the control values. CONCLUSIONS: Although
      alternative explanations such as supraspinal effects cannot be ruled out
      completely, the findings of this study are most likely explained by a specific
      presynaptic effect of propofol. Strong evidence form neurophysiologic studies
      indicates that this effect is mediated by the GABA type A receptors.

PMID- 16571978
TI  - Bupivacaine inhibits activation of neuronal spinal extracellular receptor
      activated kinase through selective effects on ionotropic receptors.
AB  - BACKGROUND: Central terminals of primary nociceptors release neurotransmitters
      glutamate and substance P, which bind to ionotropic or metabotropic receptors on
      spinal neurons to induce cellular responses. Extracellular signal-regulated
      kinases are activated by these receptors and are important modulators of pain at
      the dorsal horn. The authors investigated these pathways as potential targets for
      antinociceptive actions of local anesthetics. METHODS: The effects of bupivacaine
      on the activation of extracellular receptor-activated kinase (phosphorylation to
      pERK) in rat spinal cord slices, induced by presynaptic release (capsaicin), by
      presynaptic or postsynaptic ionotropic or metabotropic receptor activation, or by
      activation of intracellular protein kinase C or protein kinase A and also by a
      receptor-independent Ca2+ ionophore, were quantitated by immunohistochemistry,
      counting pERK-positive neurons in the superficial dorsal horn. RESULTS: Capsaicin
      (3 microm, 10 min)-stimulated pERK was reduced by bupivacaine (IC50 approximately
      2 mm, approximately 0.05%), which similarly suppressed pERK induced by the
      ionotropic glutamate receptors for N-methyl-D-aspartate and (S)-alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid but not that induced by the
      metabotropic receptors for glutamate, bradykinin, or substance P. Extracellular
      receptor-activated kinase activation by the Ca2+ ionophore ionomycin was also
      sensitive to bupivacaine, but direct activation by protein kinase A or protein
      kinase C was not. CONCLUSIONS: Bupivacaine inhibits pERK activation resulting
      from different modes of Ca2+ influx through the plasma membrane. This represents
      a postsynaptic mechanism of analgesia that occurs in parallel with impulse
      inhibition during neuraxial blockade.

PMID- 16571979
TI  - Subpopulation of dorsal horn neurons displays enhanced N-methyl-D-aspartate
      receptor function after chronic morphine exposure.
AB  - BACKGROUND: Morphine tolerance may be attributed to enhancement of glutamatergic
      neurotransmission, in particular to increased function of the N-methyl-D
      aspartate (NMDA) receptor. The cellular mechanisms responsible for these changes
      remain poorly defined. The authors identified and characterized a specific
      subpopulation of dorsal horn neurons, displaying NMDA receptor plasticity in
      response to chronic morphine administration. METHODS: The authors undertook
      current clamped and voltage clamped recordings of NMDA receptor-mediated
      responses from cultured rat dorsal horn neurons that were untreated or treated
      for 7 days with 1 or 100 microm morphine. RESULTS: Smaller (capacitance < or = 22
      pF), tonic firing neurons showed a significantly enhanced NMDA receptor-mediated
      peak current after prolonged morphine treatment, whereas larger and phasic firing
      neurons showed no enhancement. With high-concentration but not low-concentration
      morphine treatment, Mg2+ blockade of NMDA receptors at resting membrane
      potentials was reduced. Furthermore, the chronic opioid-induced increase in NMDA
      current was attenuated by pretreatment with either a mu-opioid receptor inhibitor
      (naloxone) or an NMDA receptor inhibitor (2-amino-5-phosphonovalerate) (low
      concentration > high-concentration morphine). CONCLUSIONS: In an
      electrophysiologically defined subpopulation of dorsal horn neurons, enhanced
      NMDA receptor function after chronic morphine exposure was shown to be
      mechanistically dependent on morphine concentration and sensitive to both NMDA
      and mu-opioid receptor antagonism. Therefore, these changes observed in this
      population of sensory spinal neurons can be used to study the development and
      prevention of opioid tolerance described in multiple laboratory and clinical
      reports.

PMID- 16571980
TI  - Predicting patient nonappearance for surgery as a scheduling strategy to optimize
      operating room utilization in a veterans' administration hospital.
AB  - BACKGROUND: Previous attempts at improving operating room utilization have
      generally emphasized more accurate scheduling, starting the first case on time,
      and reducing turnover time. Surgical case cancellations have largely been ignored
      except for recommendations for preoperative screening and good physician-patient
      communication to improve patient compliance. METHODS: A retrospective review of
      operating room records was initially used to identify reasons for surgical
      cancellations. This was followed by a retrospective stratified case-control study
      of patient records to identify preexisting factors that predict the failure of
      patients to appear for surgical procedures as scheduled. Factors assessed
      included demographics, type of surgical procedure, compliance with previous
      healthcare visits, substance abuse, mental illness, travel distance, and
      neurologic problems. RESULTS: The authors reviewed their operating room
      utilization and found patient nonappearance rates to be a substantial source of
      surgical cancellations. Furthermore, multivariate analysis demonstrated that
      patient nonappearance could be strongly predicted from patient noncompliance with
      clinic visits and other clinical procedures without reference to the other
      variables assessed. Further analysis of data from an independent sample of
      patients confirmed this observation. CONCLUSIONS: Noncompliance with hospital
      visits for surgical procedures can be predicted from noncompliance with other
      healthcare encounters. Surgical procedures for previously noncompliant patients
      should be booked at the end of the operating room day, when the cancellation is
      least likely to interfere with operating room flow.

PMID- 16571982
TI  - Practice advisory for intraoperative awareness and brain function monitoring: a
      report by the american society of anesthesiologists task force on intraoperative
      awareness.

PMID- 16571981
TI  - Analgesic treatment after laparoscopic cholecystectomy: a critical assessment of
      the evidence.
AB  - Acute pain after laparoscopic cholecystectomy is complex in nature. The pain
      pattern does not resemble pain after other laparoscopic procedures, suggesting
      that analgesic treatment might be procedure specific and multimodal. Randomized
      trials of analgesia after laparoscopic cholecystectomy were identified by
      systematic electronic literature searches (1985 to June 2005) supplemented with
      manual searching. The trials were categorized by well-defined criteria into high,
      moderate, or poor methodologic quality. Conclusions were based on trials of high
      and moderate methodologic quality. In total, 64 randomized analgesic trials were
      identified, comprising a total of 5,018 evaluated patients. The literature
      suggests a multimodal analgesic regimen consisting of a preoperative single dose
      of dexamethasone, incisional local anesthetics (at the beginning or at the end of
      surgery, depending on preference), and continuous treatment with nonsteroidal
      antiinflammatory drugs (or cyclooxygenase-2 inhibitors) during the first 3-4
      days. Opioids should be used only when other analgesic techniques fail.

PMID- 16571983
TI  - Gerard W. Ostheimer "what's new in obstetric anesthesia" lecture.

PMID- 16571984
TI  - Perineural infusion of local anesthetics.

PMID- 16571985
TI  - Copper kettle revisited. 1952.

PMID- 16571986
TI  - Prevention of an acute severe exacerbation of Stiff-person syndrome during
      surgery.

PMID- 16571987
TI  - Hemoglobin M (Milwaukee) affects arterial oxygen saturation and makes pulse
      oximetry unreliable.

PMID- 16571989
TI  - Does restrictive intraoperative fluid management alter outcome after
      intraabdominal surgery?

PMID- 16571990
TI  - Vaporizer-selection system malfunction in the Drager Narkomed 2C machine.

PMID- 16571992
TI  - Dexmedetomidine facilitates withdrawal of ventilatory support.

PMID- 16571994
TI  - Deep vein thrombosis after recombinant factor VIIa infusion to control severe
      recurrent postoperative bleeding.

PMID- 16571995
TI  - Perioperative treatment of patients with a history of intraoperative awareness
      and post-traumatic stress disorder.

PMID- 16571996
TI  - Society of neurosurgical anesthesia and critical care scientific meeting.

PMID- 16571998
TI  - Effects of self-administered alcohol concentration on the frequency and
      persistence of rats' attending to alcohol cues.
AB  - Observing responses produce contact with stimuli that are to be discriminated and
      have been considered an animal model of attending. In the observing-response
      procedure, alternating periods of drug availability versus extinction for one
      response are not signaled, but a second response (i.e. the observing response)
      produces stimuli signaling whether drug is available or not. This experiment
      examined the effects of the concentration of self-administered alcohol and
      increases in observing-response requirement on rats' observing alcohol stimuli.
      In addition, the effects of alcohol concentration on the persistence of observing
      were examined when alcohol was no longer available. Results showed that observing
      tracked bitonic changes in the number of alcohol deliveries rather than monotonic
      increases in total alcohol consumption resulting from increases in alcohol
      concentration. Increasing the observing-response requirement decreased the number
      of stimulus presentations earned. The resultant decreases in time spent in the
      presence of the alcohol stimulus were associated with decreases in alcohol
      consumption. During extinction of alcohol responding, observing was more
      persistent when it produced a stimulus previously associated with a higher
      alcohol concentration. Finally, responding for alcohol was more resistant to
      extinction in the presence of an observing-response-produced alcohol stimulus
      than in its absence, but did not depend on alcohol concentration. These results
      suggest that increases in the difficulty of obtaining access to alcohol cues can
      decrease alcohol consumption by reducing contact with those cues. In addition, if
      observing behavior in the present procedure is analogous to attending to alcohol
      cues, the results suggest that attending to alcohol cues is more persistent with
      cues previously associated with higher doses, and that the persistence of
      attending to alcohol cues and their impact on drinking may be dissociable.

PMID- 16572000
TI  - The effects of cannabinoids on contextual conditioned fear in CB1 knockout and
      CD1 mice.
AB  - We studied the effects of cannabinoids on contextual conditioned fear responses.
      CB1 knockout and wild-type (CD1) mice were exposed to a brief session of electric
      shocks, and their behavior was studied in the same context 24 h later. In wild
      type mice, shock exposure increased freezing and resting, and decreased
      locomotion and exploration. The genetic disruption of the CB1 receptor abolished
      the conditioned fear response. The CB1 antagonist AM-251 reduced the peak of the
      conditioned fear response when applied 30 min before behavioral testing (i.e. 24
      h after shocks) in CD1 (wild-type) mice. The cannabinoid agonist WIN-55,212-2
      markedly increased the conditioned fear response in CD1 mice, the effect of which
      was potently antagonized by AM-251. Thus, cannabinoid receptor activation appears
      to strongly promote the expression of contextual conditioned fear. In earlier
      experiments, cannabinoids did not interfere with the expression of cue-induced
      conditioned fear but strongly promoted its extinction. Considering the primordial
      role of the amygdala in simple associative learning (e.g. in cue-induced fear)
      and the role of the hippocampus in learning more complex stimulus relationships
      (e.g. in contextual fear), the present and earlier findings are not necessarily
      contradictory, but suggest that cannabinoid signaling plays different roles in
      the two structures. Data are interpreted in terms of the potential involvement of
      cannabinoids in trauma-induced behavioral changes.

PMID- 16571999
TI  - Discrete cues paired with naloxone-precipitated withdrawal from acute morphine
      dependence elicit conditioned withdrawal responses.
AB  - Acute bolus doses of morphine induce a state of acute opioid dependence as
      measured by naloxone-precipitated withdrawal. Repeated morphine and precipitated
      withdrawal experience further enhances naloxone-induced withdrawal severity,
      partly because of direct neuroadaptation to repeated morphine, and partly because
      of conditioned associations of context and withdrawal experience. To determine
      whether a discrete tone/light conditioned stimulus could elicit conditioned
      withdrawal responses in acute dependence, rats trained on a fixed-ratio-15
      operant schedule for food reward received morphine (5.6 mg/kg) 4x at daily or
      weekly intervals, with each morphine injection followed at 4 h by naloxone (1.0
      mg/kg) and an operant session. The conditioned stimulus was presented to a Paired
      group after each naloxone injection. Separate control groups experienced the
      conditioned stimulus either at a different time of the day or on a different day
      of the week than naloxone (Unpaired), received naloxone without any conditioned
      stimulus exposure [Paired-no conditioned stimulus (Paired-NO CS)] or received
      vehicle instead of naloxone before conditioned stimulus presentation (NaI-Naive).
      On the test day, all rats received vehicle before conditioned stimulus exposure.
      The conditioned stimulus alone reliably suppressed responding in Paired groups
      relative to control conditions with either daily or weekly intervals between
      conditioning sessions. The administration of morphine 4 h before conditioned
      stimulus exposure on the test day was not necessary to observe conditioned
      withdrawal. Thus, conditioned withdrawal is reliably established to discrete cues
      associated with naloxone-precipitated withdrawal from acute, infrequent (weekly)
      opioid exposure.

PMID- 16572001
TI  - Influence of intracerebroventricular administration of cannabinergic drugs on
      morphine state-dependent memory in the step-down passive avoidance test.
AB  - The effects of cannabinergic drugs on morphine state-dependent memory of passive
      avoidance task were examined in mice. Pre-training (0.25, 0.5 and 5 mg/kg) and
      post-training (5 mg/kg) administration of morphine impaired memory retrieval on
      the test day. Impairment of memory retrieval by morphine (5 mg/kg) on the test
      day was reversed by pre-test administration of the same dose of the opioid. The
      pre-test intracerebroventricular administration of the cannabinoid CB1/CB2
      receptor agonist (WIN55,212-2) (0.75 and 1 microg/mouse) not only mimicked the
      effect of pre-test morphine treatment, but also increased this action of the
      opioid. Furthermore, the pre-test intracerebroventricular administration of CB1
      receptor antagonist (AM251) (20 and 100 ng/mouse) prevented the restoration of
      memory by morphine. Pre-training administration of WIN55,212-2 (1 microg/mouse)
      led to state-dependent learning with impaired memory retrieval on the test day as
      well, which was reversed by pre-test administration of the drug (0.5, 0.75 and 1
      microg/mouse) or morphine (1 and 5 mg/kg). Restoration of impairment induced by
      WIN55,212-2 was decreased by both the opioid receptor antagonists, naloxone (0.01
      microg/mouse) and AM251 (20 and 100 ng/mouse). In conclusion, the improvement of
      memory retrieval by morphine treatment on the test day seems to be induced, at
      least in part, by the cannabinoid CB1 receptors.

PMID- 16572003
TI  - Cannabinoid effects on behaviors maintained by ethanol or food: a within-subjects
      comparison.
AB  - The cannabinoid CB1 antagonist rimonabant (SR141716A) has been proposed as a
      therapeutic agent for several addictive disorders, including alcoholism.
      Rimonabant may selectively reduce responding for an ethanol solution compared
      with an alternative. While this could represent a specific effect of CB1
      inhibition on ethanol reinforcement, this could also result from differences in
      the baseline rates of behavior or experiences between comparison groups. We
      developed a procedure in rats that allows a within-subject comparison of ethanol
      and food-maintained responding and provides well matched baseline response rates.
      We determined the effects of acute doses of rimonabant (0.3-5.6 mg/kg,
      intraperitoneal) and the CB1 agonist Delta-9-tetrahydrocannabinol (1.0-5.6 mg/kg,
      intraperitoneal) on responding for food and ethanol under a multiple fixed-ratio
      schedule. To confirm that rimonabant blocked cannabinoid receptors, the ability
      of rimonabant to antagonize Delta-9-tetrahydrocannabinol effects in the same
      subjects under the same reinforcement schedule was also determined. In contrast
      with previous reports, rimonabant did not significantly alter responding for
      ethanol or food. The effects of Delta-9-tetrahydrocannabinol on responding for
      food were completely antagonized by rimonabant, whereas Delta-9
      tetrahydrocannabinol effects on responding for ethanol were not. These results
      suggest that there may be neuroadaptation of the cannabinoid system following
      aging or chronic self-administration of ethanol.

PMID- 16572002
TI  - Discriminative stimulus effects of flumazenil: perceptual masking by baclofen,
      and lack of substitution with gamma-hydroxybutyrate and its precursors 1,4
      butanediol and gamma-butyrolactone.
AB  - Pigeons trained to discriminate 0.1 mg/kg flumazenil, proposed as an in-vivo
      model to study interactions with diazepam-insensitive gamma-aminobutyric acid
      (GABA)A receptors, were tested with various GABAergic and non-GABAergic
      compounds. As a result of its pharmacological selectivity, the model was suitable
      for further examining previously reported flumazenil-like effects of gamma
      hydroxybutyrate (GHB). Flumazenil and the GABAA negative modulator Ro 15-4513
      produced 82-100% flumazenil-appropriate responding. Diazepam and the direct
      acting GABAA agonists muscimol and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3
      ol (THIP) produced 38-64% flumazenil-appropriate responding. GHB, its precursors
      1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL), and the GABAB agonists
      baclofen and SKF97541 produced 0-24% flumazenil-appropriate responding. Baclofen
      shifted the flumazenil dose-response curve to the right and down, possibly
      involving perceptual masking of the discriminative stimulus effects of flumazenil
      by agonist activity at GABAB receptors. These masking effects of baclofen were
      blocked by the GABAB antagonist CGP35348. When CGP35348 was given together with
      GHB to block its GABAB agonist effects, GHB did not produce flumazenil
      appropriate responding. Conceivably, effects of GHB at non-GABAB receptors (e.g.
      diazepam-sensitive GABAA receptors and GHB receptors) may interfere with the
      expression of its flumazenil-like discriminative stimulus effects. The asymmetric
      substitution between GHB and flumazenil is consistent with the hypothesis that
      the discriminative stimulus effects of GHB consist of several components, not all
      of which are mimicked by flumazenil.

PMID- 16572004
TI  - Role of ventral tegmental area, periaqueductal gray and parabrachial nucleus in
      the discriminative stimulus effects of morphine in the rat.
AB  - Previous studies have produced mixed results about the role of the ventral
      tegmental area, periaqueductal gray and parabrachial nucleus in morphine
      discriminations, perhaps owing to the considerably different methodologies used.
      The purpose of the present study was to compare the roles of these three brain
      areas using the same food-reinforced discrimination protocol, to determine
      whether the schedule of reinforcement influenced maximal substitution produced by
      site-specific morphine administration and to determine whether the time course of
      substitution differed by site of morphine administration. Rats were trained to
      discriminate 3.0 mg/kg subcutaneous morphine from saline under variable interval
      15-s or fixed ratio 10 schedules of food reinforcement. Rats were then implanted
      with one cannula aimed at the lateral ventricle (intracerebroventricular) and one
      aimed at the ventral tegmental area, periaqueductal gray or parabrachial nucleus.
      Morphine discrimination curves were obtained by subcutaneous,
      intracerebroventricular and intrasite routes. When administered subcutaneously,
      morphine was equipotent in variable interval-trained and fixed ratio-trained
      rats, although it was more potent in fixed ratio-trained females than fixed ratio
      trained males. When administered intracerebroventricularly, morphine (0.3-10
      microg) engendered a maximum average of 63% drug-appropriate responding in both
      variable interval-trained and fixed ratio-trained rats; females showed
      significantly greater drug-appropriate responding than males, again under the
      fixed ratio but not under the variable interval schedule. In variable interval
      trained rats, intrasite infusions of morphine (0.3-10 microg) produced maximal
      drug-appropriate responding of approximately 57% (ventral tegmental area), 56%
      (periaqueductal gray) and 41% (parabrachial nucleus); mean maximal substitution
      was slightly (< or = 17%) greater in fixed ratio-trained rats. When injected into
      the ventral tegmental area or periaqueductal gray, but not the parabrachial
      nucleus, naloxone methiodide (2 microg) significantly decreased drug-appropriate
      responding following 3.0 mg/kg subcutaneous morphine, in both variable interval
      trained and fixed ratio-trained rats. The time course of the discriminative
      stimulus effects of morphine differed among the three brain sites: intraventral
      tegmental area morphine produced peak drug-appropriate responding by 15 min after
      injection, whereas the discriminative stimulus effects of intraperiaqueductal
      gray and intraparabrachial nucleus morphine peaked at approximately 60 min after
      injection. Taken together, these results indicate that ventral tegmental area,
      periaqueductal gray and parabrachial nucleus each play a role in the ability of
      morphine to function as a discriminative stimulus, regardless of the sex of the
      subject or the schedule under which the subjects are responding. Ventral
      tegmental area and periaqueductal gray, however, appear to be more critical than
      parabrachial nucleus in mediating the discriminative effects of systemic morphine
      in rats responding under a food reinforcement procedure. The pretreatment time
      and, to a lesser extent, the schedule of reinforcement are additional variables
      that should be considered when comparing the relative roles of different brain
      areas in drug discrimination.

PMID- 16572005
TI  - Selective effects of citalopram in a mouse model of stress-induced anhedonia with
      a control for chronic stress.
AB  - A stress-induced decrease in sucrose preference in rodents is regarded as an
      analog of anhedonia, a key symptom of depression. We investigated the effects of
      citalopram, administrated via drinking water (15 mg/kg/day), in a mouse model of
      stress-induced anhedonia. In this model, chronic stress induces anhedonia in a
      subset of C57BL/6N mice, while the remaining animals do not show a hedonic
      deficit or other depressive-like behaviors, although they are exposed to the same
      stressors as the anhedonic mice. Pre-stress and post-stress treatment with
      citalopram counteracted the development and maintenance of anhedonia and rescued
      normal floating in the forced swim test, demonstrating an antidepressant-like
      action. During the post-stress treatment, citalopram selectively increased
      sucrose preference and intake on the fourth week of treatment in anhedonic mice
      without affecting non-anhedonic animals. Citalopram also decreased elevated water
      consumption in the anhedonic group. Citalopram, administered 1 week before and
      during a 4-week stress procedure, decreased the percentage of anhedonic mice and
      reduced the increase of water intake in stressed mice. This study suggests that
      our chronic stress paradigm can serve as a model of anhedonia, in which
      antidepressant treatment is selectively effective in animals with a hedonic
      deficit.

PMID- 16572006
TI  - Body weights and plasma prolactin levels in female rats treated subchronically
      with ziprasidone versus olanzapine.
AB  - In a putative animal model of antipsychotic drug-induced weight gain, female rats
      received either vehicle, ziprasidone (2.0, 6.0, 10 mg/kg) or olanzapine (2.0
      mg/kg), orally, twice daily, for 7 days. Body weights were assessed daily and
      prolactin assayed at the end of the regimen. Ziprasidone caused significant
      weight gain, as did olanzapine, while stimulating distinct patterns of prolactin
      secretion. Thus, assessment of body weight provides only limited predictive
      validity in differentiating between weight gain-inducing and weight-neutral
      drugs.

PMID- 16572008
TI  - Does the construction material affect outcomes in long-term catheterization?

PMID- 16572009
TI  - Writing the researchable question.
AB  - Writing the researchable question is a challenging and difficult step in the
      research process, yet it is one of its most critical aspects. A clear and
      carefully and thoughtfully constructed research question helps to guide the
      research project to hit its scholarly target. To some degree, research is only as
      good as the research question and plan on which it is based. More importantly,
      from a clinical practice perspective, answering the carefully composed research
      question closes the gaps between what is known and what needs to be known about
      nursing care and resolves the discrepancy between the way things are and what
      they ought to be for better patient care.

PMID- 16572010
TI  - Issues and challenges in staging of pressure ulcers.
AB  - Wound assessment is a key element of effective wound care, and assessment of
      pressure ulcers includes accurate determination of wound stage. Although the
      original staging system established by Shea was based on his understanding of the
      pathology involved in pressure ulcer development, subsequent staging systems (and
      the one currently in use) were intended simply to establish the level of tissue
      damage. Recently, clinicians have drawn attention to numerous limitations
      associated with the current staging system, including the inability to
      differentiate between an inflammatory response involving intact skin and a deep
      tissue injury (deep bruising) underneath intact skin. This is a clinically
      significant difference because clinicians have noted that most inflammatory
      responses resolve with intervention, whereas most areas of deep tissue injury
      progress to full-thickness ulcers even when appropriate intervention is provided.
      A second area of controversy involves partial-thickness (Stage 2) lesions;
      because many of these lesions are caused by maceration and/or friction (as
      opposed to pressure) clinicians are frequently unclear regarding which of these
      lesions should be staged. In response to these concerns, the National Pressure
      Ulcer Advisory Panel convened a consensus forum and published white papers to
      clearly outline the issues; they solicited clinician feedback on the white papers
      and the Wound, Ostomy, Continence Nurses Society provided a written response.
      This article summarizes the key points of the white papers, WOCN Society
      response, and consensus forum discussion.

PMID- 16572012
TI  - A retrospective chart review of risk factors for extravasation among neonates
      receiving peripheral intravascular fluids.
AB  - PURPOSE: To identify variables associated with extravasation and resulting tissue
      damage in neonates with peripheral intravascular therapy. DESIGN: A retrospective
      chart review was completed. SETTING AND SUBJECTS: Randomly selected medical
      records of 25 neonates admitted to a neonatal intensive care unit from January
      2003 through April 2004 and who experienced peripheral intravascular infiltration
      were examined. INSTRUMENTS: The Neonatal Tissue Extravasation Tool was created to
      reflect common descriptive variables of the neonatal population and infused
      solutions used in their care. Tissue damage was classified with the scale from
      the Task Force of Pediatric Nursing Research Committee, 1994. RESULTS: Charts of
      15 female and 10 male infants 24 to 39.6 weeks old were reviewed. Extravasation
      was not significantly related to age, weight, or sex. The most common intravenous
      medications were total parenteral nutrition (n = 19) and calcium (n = 18).
      Peripheral intravenous sites were secured with tape. The sites of the infiltrate
      were the arm (n = 16), foot/leg (n = 5), and scalp (n = 3) (one not recorded).
      Stages 0 (absence of redness, pain, swelling; flushes with ease) (n = 11) and 4
      (severe swelling; blanching, pain, skin breakdown, etc.) (n = 6) were the most
      common stages. The site of the infiltrate was measured and care described in only
      9 neonates. CONCLUSIONS: The intravascular solutions causing the most extensive
      damage from extravasation were similar to those reported in other studies. No
      other potential risk factors were identified, but poor documentation about the
      extravasation site and management of skin damage hampered data collection via
      retrospective chart review.

PMID- 16572013
TI  - Do registered nurses perceive the anchoring of indwelling urinary catheters as a
      necessary aspect of nursing care? A pilot study.
AB  - OBJECTIVE: To determine if registered nurses perceive the stabilization of
      indwelling urinary catheters as a necessary aspect of care. DESIGN: Descriptive
      exploratory study. SETTING AND SUBJECTS: Eighty-two medical-surgical and critical
      care registered nurses currently practicing in a community medical center.
      INTERVENTIONS: A new instrument, the Catheter Anchoring Survey, was designed by
      the primary investigator and submitted for face and content validity to 8
      certified continence specialists. A convenience sample of 82 medical-surgical and
      critical care nurses voluntarily completed the survey. RESULTS: Ninety-eight
      percent of the nurses agreed that securing indwelling urinary catheters was a
      necessary aspect of nursing care, but this response was not congruent with the
      prevalence data obtained before questionnaire completion. CONCLUSIONS: The
      majority of nurses surveyed agreed that catheter stabilization is an important
      aspect of nursing care, but this perception did not concur with current practice.
      Further research is needed to determine if catheter stabilization should be the
      standard of care.

PMID- 16572014
TI  - Duration of short-term indwelling catheters--a systematic review of the evidence.
AB  - OBJECTIVE: A systematic review on the effect of duration of catheterization on
      urinary retention. MATERIALS AND METHODS: Published and unpublished randomized
      and nonrandomized control trials from January 1966 to July 2004 comparing the
      effects of duration of catheterization on patient outcomes were systematically
      reviewed. Relative risks (RR) for dichotomous data and a weighted mean difference
      for continuous data were calculated with 95% confidence intervals (CI). Where
      synthesis was inappropriate, a narrative overview was undertaken. RESULTS: Eight
      trials were included. Two trials on patients following urethrotomy demonstrated
      no statistically significant difference in the number of patients developing
      restenosis, epididymitis, or urethral pain at any follow-up periods. Two trials
      comparing removal of the indwelling urethral catheter within 24-48 hours to usual
      surgical criteria after transurethral surgery demonstrated no statistically
      significant difference in the number of patients requiring recatheterization.
      However, significant reduction in the length of hospitalization was reported
      after removal of the indwelling urethral catheter within 24-48 hours. An
      increased risk of urinary tract infection was found when the catheter was removed
      after 48 hours. Catheter removal on day 1 compared to day 3 after vaginal or
      retropubic surgery demonstrated no statistically significant difference in
      urinary retention or urinary tract infection. CONCLUSIONS: No significant
      differences in patient outcome were found, but the timing of catheter removal is
      a balance between avoiding infection by early removal and circumventing voiding
      dysfunction by later removal. Shorter catheterizations appear to reduce mean
      length of hospital stay.

PMID- 16572016
TI  - Does evening removal of urinary catheters shorten hospital stay among general
      hospital patients? A randomized controlled trial.
AB  - OBJECTIVE: Literature indicates that removing urinary catheters at midnight
      facilitates earlier discharge among urology patients, but the effect of evening
      removal on the general patient population is unknown. The objective of this study
      was to investigate whether removing a urinary catheter at 22.00 hours compared to
      06.00 hours among a general hospital population would lead to earlier hospital
      discharge. DESIGN: Randomized controlled trial. SETTING AND SUBJECTS: The study
      was conducted in a large tertiary hospital in Brisbane, Australia. Two hundred
      and ten general surgical and medical patients who had an indwelling catheter as
      part of their routine care were included. RESULTS: Length of hospital stay after
      catheter removal was not significantly affected by the timing of its removal
      among general hospital patients: mean hours morning 186.1; mean evening 209.3, (P
      = .309). In a cohort of surgical patients, the hospital stay was shorter in the
      evening removal group (mean hours morning 186.1; mean evening 209.3), but this
      result was not statistically significant (P = .127). Patients in the evening
      group were more likely to have a longer time period between catheter removal and
      the first postcatheter void, mean hours morning, 3.76 vs evening, 4.89 (t = 
      2.59, CI - 1.99 to -0.27). Timing of removal of the urinary catheter had no
      effect on the volume of the first void, mean volume morning, 214.7 mL vs evening,
      221.4 mL. Twenty-five (12.1%) patients were recatheterized, but the rate of
      recatheterization between groups was similar. There were no differences in
      postdischarge problems between groups. CONCLUSION: Among general hospital
      patients, removing an indwelling urinary catheter at 22:00 hours does not shorten
      the length of stay and is effective in increasing the time to first void.

PMID- 16572017
TI  - Awareness of urine flow in people with long-term urinary catheters.
AB  - OBJECTIVES: The purpose of this study is to acquire knowledge about urine flow in
      relation to fluid intake and urinary output, catheter blockage, and urinary tract
      infection in people with long-term urinary catheters. DESIGN: This was a
      community-based exploratory and descriptive study. SETTING AND SUBJECTS: The
      research was conducted in the homes of participants, who were interviewed in
      North Carolina from October 2002 to June 2003. The sample included 21 males and 9
      females, aged 23-96 years; almost half were members of minority groups.
      INSTRUMENTS: A urinary diary was used, including intake and output recordings and
      narrative data, as well as a semistructured interview schedule. METHODS: Three
      day fluid intake and urinary diary data were collected, followed by face-to-face
      tape-recorded interviews in participants' homes related to catheter experiences
      and practices. Analysis of data involved descriptive statistics and content
      analysis of narrative data. RESULTS: Although urine flow frequently was disrupted
      by urinary sediment or kinks in tubing, urinary tract infection was significantly
      related only to traumatic catheter manipulations or catheter blockage. Catheter
      problems associated with urinary tract infection included: (1) "rough" catheter
      insertions, (2) "difficult" insertions, and (3) catheter blockage. CONCLUSION:
      Self-monitoring of urine flow may help prevent urinary tract infection episodes
      through careful attention to catheter position and by preventing blockage.
      Further study is needed to fully understand the role of fluid intake and
      determine what causes traumatic catheter insertions.

PMID- 16572020
TI  - Surgical wound case studies with the versatile 1 wound vacuum system for negative
      pressure wound therapy.
AB  - Negative pressure wound therapy consists of a wound dressing, a drainage tube
      inserted into the dressing, an occlusive transparent film, and a connection to a
      vacuum source that supplies the negative pressure. A new product called the
      Versatile 1 Wound Vacuum System (BlueSky Medical, La Costa, Calif) is available
      for negative pressure wound therapy. This article describes the application,
      management, and effectiveness of the Versatile 1 in 3 cases where the patients
      have all undergone surgical debridement.

PMID- 16572023
TI  - Encouraging increased physical activity in the elderly.

PMID- 16572024
TI  - Arthroscopy of the hip joint: an overview.
AB  - Hip arthroscopy is a procedure that is gaining popularity for treating hip pain
      related to intraarticular cartilage lesions or loose bodies. It offers an
      alternative procedure that can decrease or eliminate hip pain and increase a
      patient's ability to do activities of daily living. This article provides a
      comprehensive overview of hip arthroscopy and also addresses the anatomy of the
      hip, appropriate diagnoses for the procedure, operative considerations and
      postoperative teaching.

PMID- 16572026
TI  - Developmental dysplasia of the hip: nursing implications and anticipatory
      guidance for parents.
AB  - Developmental dysplasia of the hip (DDH) is a comprehensive term used to describe
      an abnormal relationship between the femoral head and the acetabulum.
      Developmental dysplasia of the hip includes a very wide spectrum of abnormality
      from a frank dislocation (very unstable) to a stable hip with a slightly shallow
      acetabulum. As many of these findings may not be present at birth, the term
      developmental more accurately reflects the biologic features than does the term
      congenital. Despite the recent increased awareness of DDH and the importance of
      thorough screening programs, hip dysplasia continues to be a frequently missed
      diagnosis in pediatrics. Earlier detection and diagnosis of DDH is associated
      with a much more successful and less invasive outcome.

PMID- 16572028
TI  - Physical and psychological variables that influence pain in patients with
      fibromyalgia.
AB  - BACKGROUND: Fibromyalgia is a syndrome of chronic pain. Its etiology is unknown
      and treatment is not well defined. PURPOSE: The purpose of this study was to
      determine the influence of specific variables on pain in 107 women with
      fibromyalgia. METHODS: Data collection included two pain measurements
      administered by the researcher, four survey questionnaires self-administered by
      the participants (measuring activity, fatigue, depression, and demographic data),
      and three measures of physical fitness for flexibility, strength, and endurance.
      FINDINGS: Fatigue, pelvic pain, and physical trauma explained 23% of the variance
      in sensory pain; activity, depression, and pelvic pain explained 23% of affective
      pain; and a flare-up of symptoms and depression explained 25% of the intensity of
      pain experienced by the participants. CONCLUSION: Nurses should consider
      decreasing depression and fatigue and increasing activity so that fibromyalgia
      pain may be lessened during care.

PMID- 16572030
TI  - The use of Tai Chi to improve health in older adults.
AB  - Tai Chi is a slow and gentle exercise that is suitable for older adults with
      chronic illness. This exercise offers the benefits of flexibility, muscle
      strengthening, and endurance training. Tai Chi has the capability of improving
      the health of elders without exacerbating existing impairments. Therefore, older
      adults may be more inclined to participate in and maintain an exercise program.
      The purpose of this article is to (1) compare Tai Chi to muscle-strengthening and
      aerobic exercise, (2) describe possible mechanisms for the effects of Tai Chi on
      factors that contribute to disability, and (3) identify nursing interventions to
      promote the use of Tai Chi.

PMID- 16572031
TI  - An insider perspective of daily stress and coping in elders with arthritis.
AB  - BACKGROUND: Elders living with arthritis perceive chronic daily stress associated
      with a loss of function. Daily stress has a significant effect on the prediction
      of depression and decreased life satisfaction in older persons. However, little
      is known about the nature of the daily stress and coping process from their
      personal viewpoint. PURPOSE: This study explores stressors in daily life, coping
      strategies, and social support resources from the perspective of older adults
      with arthritis. METHODS: Thirteen older adults with arthritis participated in
      semistructured, individual interviews. Content analysis of the interview
      transcriptions was used. FINDINGS: Results revealed six sources of stress in the
      daily life of the participants: health, routine tasks, family issues, financial
      management, social relationships, and living conditions. Three major strategies
      of coping with daily stress emerged: cognitive efforts, diversional activities,
      and assertive actions. Participants reported a wide range of support resources to
      deal with daily stress. CONCLUSION: Recommendations for health professionals in
      assisting clients to minimize the impact of daily stress on mental health by
      assessing the sources of stress, improving cognitive-behavioral coping
      techniques, and locating resources are given.

PMID- 16572032
TI  - Who speaks for the vulnerable?
AB  - Feeling vulnerable is a common human experience; everyone has probably felt
      powerless or unable to exert personal control in various situations. Lacking
      information, feeling stigmatized, being unable to control what is happening, or
      lacking access to services may lead people to have a heightened sense of
      vulnerability. They may wonder what rights they have, whether they have been
      stripped of their rights, or whether anyone cares about their situation. Although
      a more consumer-oriented approach is being used in many healthcare facilities,
      patients do not know how to get the help they need or to whom to turn for help.
      Therefore, the purposes of this article are to explore the concept of
      vulnerability, discuss advocacy as an ethical response for nurses, and offer
      recommendations for creating an ethical environment that supports efforts of
      nurses to act as advocates and uphold the rights of patients and families.

PMID- 16572033
TI  - Cast abscess: a case report.
AB  - This report describes a case in which a pediatric patient wounded his ankle when
      he stuck an object inside the cast while trying to scratch himself. The wound
      became infected and resulted in a limb-threatening abscess. Although most
      patients treated with casts do not have any significant problems, it is important
      to emphasize cast care instructions to young patients and their parents. In
      addition, it may be equally important to advise patients about safe methods to
      alleviate itching, such as blowing cool air under the cast. In this way, the risk
      of serious infectious complications can be minimized.

PMID- 16572034
TI  - The pathogenesis of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is an autoimmune disease that causes inflammation in
      the tissues of the brain, endothelial cells, gastrointestinal/genitourinary
      (GI/GU), joints, kidneys, muscles, and skin. Lupus comprises a range of
      multisystem disorders involving the deposition of aberrant immune complexes into
      tissues. Inflammation occurs as a result of autoantibodies attacking organ
      systems. The pathogenesis of systemic lupus erythematosus is presented.

PMID- 16572037
TI  - Molecular epidemiology of recently emergent ciprofloxacin-resistant Neisseria
      gonorrhoeae in South Africa.
AB  - OBJECTIVES: Syndromic management guidelines for male urethritis syndrome and
      female discharge syndrome (nonpregnant) in South Africa advocate the use of
      ciprofloxacin for potential infection with Neisseria gonorrhoeae. In 2003,
      reports of clinical failure of gonorrhea following ciprofloxacin treatment
      prompted a clinic-based surveillance to detect the presence of resistant
      isolates. STUDY: Urethral samples for the isolation of N gonorrhoeae were
      obtained from consecutive male patients with urethral discharge attending the
      largest sexually transmitted disease clinic in KwaZuluNatal. Molecular typing of
      isolates was performed by means of N gonorrhoeae multiantigen sequence typing (NG
      MAST). RESULTS: Of 139 isolates, 31 (22%) were resistant to ciprofloxacin
      (minimum inhibitory concentration >or=1 mg/l). NG-MAST revealed novel, as well as
      previously described, sequence types (ST). The largest cluster of our isolates
      belonged to ST 217. This ST has been reported among ciprofloxacin-resistant
      isolates from Europe. CONCLUSION: : The results underscore the urgency of review
      of the current treatment guidelines for discharge disease in KwaZuluNatal.

PMID- 16572038
TI  - The impact of natural history parameters on the cost-effectiveness of Chlamydia
      trachomatis screening strategies.
AB  - OBJECTIVE/GOAL: To understand the potential impact of assumptions about the
      natural history of untreated Chlamydia trachomatis on the cost-effectiveness of
      screening strategies. STUDY DESIGN: Using a previously developed state-transition
      model, we explored how alternative assumptions about the natural history of
      disease following infection affect the estimated cost-effectiveness of screening
      for U.S. women. The analysis was conducted from a modified societal perspective
      and incorporated a lifetime analytic horizon. RESULTS: Different natural history
      assumptions affect cost-effectiveness outcomes. Assumptions about the combined
      risk of persistent and repeat infections have the greatest impact on the
      composition of optimal screening strategies, whereas assumptions about the risk
      of pelvic inflammatory disease most greatly influenced the magnitude of
      incremental cost-effectiveness ratios. CONCLUSIONS: Priorities for future C
      trachomatis research should include better estimates of the risk of pelvic
      inflammatory disease, persistence, and repeat infection. Better delineation of
      these variables will permit improved evaluation of potential screening
      activities.

PMID- 16572040
TI  - Pharyngeal Gonorrhea in female sex workers: Response to a single 2-g dose of
      azithromycin.
AB  - OBJECTIVES: A sharp increase in the incidence of gonorrhea has been observed in
      Tel Aviv, Israel, since 1999. Almost one half of interviewed patients admitted
      contracting the infection from a sex worker. In two thirds of the cases, oral sex
      (fellatio) was the most probable route of acquiring the disease. In the current
      study, we assessed the prevalence of pharyngeal gonorrhea among sex workers in
      Tel Aviv and evaluated the efficacy of a single 2-g dose of azithromycin in
      eradicating the infection. METHODS: Throat specimens were obtained for gonococcal
      culture from 301 female sex workers practicing in brothels. A questionnaire
      covering demographic and sexual behavior information was administered to all
      participants, and a single 2-g dose was administered orally under supervision.
      Women with positive cultures were reexamined a week later for eradication of
      Neisseria gonorrhoeae. RESULTS: N gonorrhoeae was isolated from 27 women (9%).
      The median age of women with pharyngeal gonorrhea was 23 years (range, 18-32
      years); 85% were born in former Soviet Union (mostly Russia, Ukraine, Moldavia).
      Regular condom use in vaginal sex was reported by 88% of the participants,
      whereas only 60% reported always using condoms in oral sex. All isolates were
      susceptible to azithromycin (MIC < or = 0.5 microg/ml). Gonococci were eradicated
      in 20/21 individuals (95%). CONCLUSION: A high carriage rate of gonococci in the
      throat and a low rate of condom use in oral sex were documented among sex workers
      in Tel Aviv. A single 2 g dose of azithromycin was very effective in eradicating
      gonococci from the throat.

PMID- 16572039
TI  - Human papillomavirus infection among sexually active young women in the United
      States: Implications for developing a vaccination strategy.
AB  - OBJECTIVES: Population-level data on prevalence and distribution of human
      papillomavirus (HPV) types in the United States are necessary to guide optimal
      vaccination strategies. STUDY: Urine specimens from 3262 women ages 18 to 25 in
      the National Longitudinal Study of Adolescent Health (Wave III) were tested and
      typed for HPV. Poststratification sampling weights generated nationally
      representative estimates. RESULTS: Overall HPV prevalence was 26.9% and as high
      as 14.3% among women with 1 lifetime partner but did not vary by geographic
      region. High-risk types were detected in 20%; approximately 10% were infected
      with types in current candidate vaccines. HPV infection was independently
      associated with mixing sex with alcohol, a black partner, >3 lifetime sex
      partners, being single, and illegal drug use. Having a current sex partner and
      receptive oral sex were inversely associated with HPV. CONCLUSION: HPV prevalence
      was high throughout the country, even among women with only 1 lifetime partner,
      suggesting early and widespread rather than targeted immunization of young women.

PMID- 16572041
TI  - Two methods of self-sampling compared to clinician sampling to detect
      reproductive tract infections in Gugulethu, South Africa.
AB  - OBJECTIVES: To assess the validity, feasibility, and acceptability of 2 methods
      of self-sampling compared to clinician sampling during a speculum examination.
      GOAL: To improve screening for reproductive tract infections (RTIs) in resource
      poor settings. STUDY DESIGN: In a public clinic in Cape Town, 450 women underwent
      a speculum examination and were randomized to self-sample with either a tampon or
      vaginal swabs. All specimens were tested for the same pathogens using the same
      diagnostic tests. RESULTS: Self-sampling resulted in satisfactory validity for N
      gonorrhoeae, C trachomatis, bacterial vaginosis, and Candida species (tampons and
      swabs) and high-risk human papillomavirus (swabs only) when tested with molecular
      tests or microscopy, but not for T vaginalis by culture. Self-sampling was
      feasible and acceptable, but some women preferred speculum examinations, which
      allow the clinician to view the vagina and cervix. CONCLUSIONS: Although self
      sampling should not replace speculum examinations in all circumstances, it should
      be explored further as an RTI screening strategy.

PMID- 16572043
TI  - Comparison of experimental and numerical muscle fiber conduction velocity (MFCV)
      distribution around the end-plate zone and fiber endings.
AB  - BACKGROUND: The distribution of muscle fiber conduction velocity (MFCV) estimated
      from surface myoelectric signals differs depending on the recording electrode
      locations. It is assumed in this study that the irregular values of MFCV may be
      estimated around the end-plate zone and the fiber endings due to effect of unique
      interference property of myoelectric signals, and its hypothesis is confirmed
      experimentally and numerically in consideration of the waveform characteristics
      of surface myoelectric signals. MATERIAL/METHODS: In experimental study, the
      surface myoelectric signals are recorded by array electrodes during voluntary
      isometric contraction in biceps brachii muscle. In the numerical study, the
      surface myoelectric signals in consideration of the interference property of some
      motor unit activities are calculated from the current dipole model which
      simulated the firing features of muscle fiber from end-plate zone to fiber
      endings. MFCV is estimated by the technique of cross-correlation. Maximum
      correlation coefficient (Rxy(Ts)) and amplitude ratio (AMPratio) are used to
      evaluate similarity and attenuation rate between traveling signals. RESULTS: In
      both results of experimental and numerical studies, the MFCV significantly
      increase when both Rxy (Ts) and AMPratio decrease around the end-plate zone and
      fiber endings although three parameters denote constant values in the locations
      other than the end-plate zone and the fiber endings. The high correlativity is
      recognized between the experimental and numerical data for MFCV, Rxy (Ts), and
      AMPratio. CONCLUSIONS: Therefore, it is demonstrated by experimental and
      theoretical studies that MFCV, Rxy(Ts), and AMPratio are influenced by irregular
      waveform properties depending on both positions of the end-plate and fiber
      endings.

PMID- 16572042
TI  - Alcohol and drug use and related disorders: An underrecognized health issue among
      adolescents and young adults attending sexually transmitted disease clinics.
AB  - OBJECTIVES: The objectives of this study were to describe patterns of alcohol and
      drug use disorders among young persons attending a public sexually transmitted
      disease (STD) clinic and to determine their associations with sexual risk
      behaviors and STDs. STUDY DESIGN: Four hundred forty-eight men and women aged 15
      to 24 who were attending an urban STD clinic completed an interviewer
      administered questionnaire that assessed a broad range of substance use in
      general and for alcohol and marijuana use disorders. RESULTS: Overall, 42.9% had
      an alcohol or marijuana use disorder (51.6% of males and 34.2% of females),
      whereas 30.6% had a confirmed STD. Participants with a substance use disorder
      were significantly more likely to have multiple sexual partners (odds ratio [OR]
      = 2.3; 95% confidence interval [CI] = 1.5-3.4), to be inconsistent condom users
      (OR = 3.1; 95% CI = 1.5-6.3), and to have an STD (OR = 1.7; 95% CI = 1.1-2.6).
      CONCLUSIONS: Among young STD clinic attendees, substance use disorders were more
      common than confirmed STDs. STD clinics may be an appropriate setting to screen
      for and address substance use disorders in young persons.

PMID- 16572044
TI  - Grape seed proanthocyanidin extract (GSPE) and antioxidant defense in the brain
      of adult rats.
AB  - BACKGROUND: Proanthocyanidin (PA) is a naturally occurring antioxidant from grape
      seed extract. The present study aims at assessing the neuroprotective effects of
      grape seed proanthocyanidin (GSPE) on the cerebral cortex (CC), cerebellum (CB),
      and hippocampus (HC) in the adult rat brain. MATERIAL/METHODS: GSPE was orally
      administered at 25, 50, and 75 mg per kg body weight daily and for a total period
      of 9 weeks. Antioxidant enzymes (AOEs), superoxide dismutase (SOD), and catalase
      (CAT) were analyzed along with malondialdehyde (MDA) and protein carbonyl content
      (PCC) as markers of lipid peroxidation (LPO) and protein oxidation (PO). The
      cholinergic system was studied by analyzing choline acetyl tranferase (ChAT) and
      acetylcholine esterase (AChE) activites along with acetylcholine content (ACh).
      RESULTS: The results obtained revealed an increased SOD activity in the 75-mg PA
      supplemented animals, with a substantial decrease in MDA and PCC. The cholinergic
      neurotransmittary system analysis showed increased ChAT activity indicative of
      increased Ach content in the supplemented animals and the increase was more in
      the 75-mg PA group with a concomitant and moderate decrease in AChE activity.
      Regional changes were more with reference to HC. CONCLUSIONS: Our study shows
      that PA intake in moderately low quantity is effective in up-regulating the
      antioxidant defense mechanism by attenuating LPO and PO. Changes in the
      cholinergic system, however, indicate an increase in the ACh concentration with a
      moderate reduction in AChE activity, suggesting further that PA may have a potent
      role in enhancing cognition in older rats.

PMID- 16572045
TI  - Inhibition of phagosome maturation and survival of Mycobacterium avium subspecies
      paratuberculosis in polymorphonuclear leukocytes from Crohn's disease patients.
AB  - BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is an
      intracellular pathogen that is known to parasitize macrophages. MAP is the known
      etiological agent of Johne's disease and implicated in the etiology of Crohn's
      disease. MATERIAL/METHODS: In this study, the survival of human-derived MAP
      isolate following phagocytosis was evaluated using murine macrophage cell line
      J774A.1 and polymorphonuclear cells (PMNC's) from six Crohn's disease patients.
      PMNC's from five healthy individuals and four ulcerative colitis patients, as
      well as Escherichia coli and Mycobacterium tuberculosis, were included as
      controls (MOI 10:1). Maturation of the phagosome was determined by evaluating the
      presence of stage specific markers on the surface of the phagosomal membrane. The
      endosomal protein, transferrin receptor, and the lysosomal protein, Lamp-1, were
      then immunostained with Cy-5 conjugated secondary antibodies, and colocalization
      of bacteria with each marker was evaluated separately using confocal scanning
      laser microscopy (CSLM). RESULTS: In both models, colocalization of viable MAP
      and M. tuberculosis with the early endosomal marker occurred with a higher
      frequency than did association with the late lysosomal marker, as compared to
      live E. coli, and all dead bacterial species. Using differential live/dead
      staining and fluorescent microscopy, survival of M. tuberculosis and MAP was
      calculated to be 85% and 79%, respectively compared to only 14% for E. coli.
      CONCLUSIONS: Overall, MAP survival in murine macrophages and human PMNCs appears
      to mimic M. tuberculosis, suggesting the ability of this microorganism to resist
      phagolysosome fusion, by maintaining association with the early endosomes. The
      data supports MAP virulence in humans.

PMID- 16572046
TI  - Physiologic microcirculation of the heterotopically transplanted rat liver with
      portal vein arterialization depending on optimal stent diameter.
AB  - BACKGROUND: Clinical experience with portal vein arterialization (PVA) in liver
      transplantation is controversial. One reason for this is the lack of standardized
      flow regulation. The present experiments aimed to establish flow regulation in
      the arterialized portal vein for heterotopic auxiliary liver transplantation
      (HALT), to obtain physiological portal blood flow, and to compare this technique
      with orthotopic liver transplantation. MATERIAL/METHODS: Lewis rats were divided
      into 7 groups (n = 8 transplantations/group). Group: A I-IV: In HALT, the portal
      vein was anastomosed to the right renal artery using stents with different
      diameters (0.2, 0.3, 0.4, 0.5 mm). Afterwards, HALT with PVA using the stent
      diameter that had achieved the most physiological portal blood flow (group B II)
      was compared with orthotopic liver transplantation with porto-portal anastomosis
      (group B III) and to the sham group (B I). RESULTS: After reperfusion, only the
      0.3 mm stent resulted in an average blood flow in the arterialized portal vein in
      HALT which was within the normal range (1.7+/-0.4 ml/min/g liver weight). The
      parameters of microcirculation and early graft function were significantly better
      in group B II than in group B III (functional sinusoidal density: 335+/-48 vs.
      224+/-31/cm, diameter of sinusoids: 6.4+/-0.6 vs. 5.2+/-0.6 microm, diameter of
      postsinusoidal venules: 31.1+/-3.3 vs. 25.5+/-2.0 microm, bile-production: 27+/-8
      vs. 19+/-5 microl/h/g liver weight). CONCLUSIONS: Using an optimal stent diameter
      in HALT with portal vein arterialization, an adequate flow-regulation can be
      achieved. Avoiding portal hyper- and hypoperfusion, good results for
      microcirculation and early graft function can be obtained.

PMID- 16572047
TI  - The presentation and organization of adaptive cytoprotection in the rat stomach,
      duodenum, and colon. Dedicated to Andre Robert the founder of the concept of
      cytoprotection and adaptive cytoprotection.
AB  - BACKGROUND: Adaptive cytoprotection could be demonstrated in lesion attenuation
      within the whole gastrointestinal tract, in particular sequences, with onset and
      duration longer than the initial short-lasting period (i.e. one hour) defined by
      Robert in the stomach only. MATERIAL/METHODS: Adaptive cytoprotection possibly
      appeared and lesions were attenuated when the stomach, duodenum or colon, in
      various combinations and sequences, were challenged with initial (mild) and/or
      final (strong) irritants over a two-week period. Rats were challenged with the
      mild or strong irritants 25% or 96% ethanol intragastrically 1 ml/rat (stomach)
      and cysteamine 40 mg or 400 mg/kg subcutaneously (duodenum), or intrarectally
      (colon). To postulate the prostaglandin relationship known in Robert's
      cytoprotection and adaptive cytoprotection, indomethacin (1 mg/kg subcutaneously)
      was given simultaneously with the second challenge. RESULTS: Administering the
      mild and strong irritant protocols within the same part of the gastrointestinal
      tract, adaptive cytoprotection presents in the stomach (1 h to 14 days), duodenum
      (2 h to 14 days), but not in the colon. With these protocols applied to different
      parts of the gastrointestinal tract, adaptive cytoprotection cross-reaction was
      evident in the stomach-duodenum, duodenum-stomach (1 h-14 days and 2 h-14 days),
      stomach-colon, and duodenum-colon (both 2-24 hours), but not in the colon-stomach
      or colon-duodenum. This protection was fully antagonized with indomethacin.
      CONCLUSIONS: As observed for a day and even weeks, stomach-duodenum-colon
      adaptive cytoprotection is an important new defensive phenomenon.

PMID- 16572048
TI  - Post-traumatic stress disorder in Polish stroke patients who survived Nazi
      concentration camps.
AB  - BACKGROUND: Many persons who survived Nazi concentration camps are now in
      advanced age, so that rehabilitation centers in Poland are seeing increasing
      numbers of such patients, especially after strokes. In many cases, the process of
      rehabilitation is severely hampered by Post-Traumatic Stress Disorder (PTSD),
      while the neuropsychological consequences of the stroke itself often evoke
      traumatic memories and simultaneously disorganize or destroy the patient's
      previous coping mechanisms. The present study describes the program developed by
      the authors for concentration camp survivors in post-stroke rehabilitation,
      including the use of art therapy and specially prepared films to help the
      patients cope with PTSD. MATERIAL/METHODS: The experimental group (KL) consisted
      of 8 such patients (4 men, 4 women, average age 79.1+/-4.28) with mild post
      stroke aphasia who went through the PTSD program, while the comparison group (C)
      included 8 post-stroke patients, matched for age and gender, who were not
      concentration camp survivors and showed no premorbid symptoms of PTSD. All
      subjects were tested at baseline and again 3 months later, using structured
      interview and observation, self-rating scales for three basic negative emotions
      (anger, anxiety and sadness) and the Frustration and Aggression Test for the
      Disabled. RESULTS: The results showed significant differences between the groups
      at baseline, while at follow-up the differences between groups had changed in
      both extent and distribution. CONCLUSIONS: Qualitative analysis of the results
      allows for some important observations about the etiology and course of PTSD in
      these persons.

PMID- 16572050
TI  - Predicting fear of heights, snakes, and public speaking from multimodal classical
      conditioning events.
AB  - BACKGROUND: Two hundred fifty one men and women participated in a study of the
      prediction of fear of heights, snakes, and public speaking by providing
      retrospective accounts of multimodal classical conditioning events involving
      those stimuli. The fears selected for study represent those believed by some to
      be innate (i.e., heights), prepared (i.e., snakes), and purely experientially
      learned (i.e., public speaking). This study evaluated the extent to which
      classical conditioning experiences in direct, observational, and verbal modes
      contributed to the prediction of the current level of fear severity.
      MATERIAL/METHODS: Subjects were asked to describe their current level of fear and
      to estimate their experience with fear response-augmenting events (first- and
      higher-order aversive pairings) and fear response-moderating events (first- and
      higher-order appetitive pairings, and pre- and post-conditioning neutral
      presentations) in direct, observational, and verbal modes. RESULTS: For each
      stimulus, fear was predictable from direct response-augmenting events and
      prediction was enhanced by the inclusion of response-moderating events.
      Furthermore, for each fear, maximum prediction was attained by the addition of
      variables tapping experiences in the observational and/or verbal modes.
      CONCLUSIONS: Conclusions are offered regarding the importance of including
      response-augmenting and response-moderating events in all three modes in both
      research and clinical applications of classical conditioning.

PMID- 16572049
TI  - Epistatic effects between two genes in the renin-angiotensin system and systolic
      blood pressure and coronary artery calcification.
AB  - BACKGROUND: Coronary artery calcification (CAC) is an important indicator of
      future coronary artery disease events. Since elevated blood pressure (BP) is an
      important predictor of CAC, genetic polymorphisms in the renin-angiotensin system
      and their interaction may play a role in explaining CAC quantity variation.
      MATERIAL/METHODS: As part of the Epidemiology of Coronary Artery Calcification
      Study, 166 asymptomatic women and 166 asymptomatic men were genotyped for the
      insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene
      and the -6 promoter polymorphism of the angiotensinogen (AGT) gene. We used a
      novel method to detect gene-gene interaction and compared it to the standard two
      way analysis of variance (ANOVA) method. RESULTS: Based on a two-way ANOVA model,
      there was no evidence for epistasis for either systolic BP or CAC in either men
      or women. However, using a novel method, we found evidence of significant gene
      gene interaction in systolic BP in men and gene-gene interaction in both systolic
      BP levels and CAC quantity in women. CONCLUSIONS: Our study demonstrates that new
      methods of assessing epistasis maybe important in understanding the complex
      genetics of systolic blood pressure as well as subclinical coronary
      atherosclerosis.

PMID- 16572051
TI  - Sleep quality of patients with acute myocardial infarction outside the CCU
      environment: a preliminary study.
AB  - BACKGROUND: Environmental factors have been implicated as major causes of sleep
      disruption in patients in critical care units, including coronary care units
      (CCU). We hypothesized that myocardial infarction may disturb sleep architecture
      regardless of the surrounding environmental factors. MATERIAL/METHODS: Twenty
      consecutive patients with a first-ever acute myocardial infarction (AMI) who were
      not on sedation or ionotropes underwent a full polysomnography (PSG) in our sleep
      disorders center, away from the CCU environment, within three days of AMI, with a
      follow-up PSG performed six months later. During patient stay in the CCU, each
      resided in a single room in which normal light-dark exposure was maintained.
      RESULTS: The 20 patients with AMI consisted of 18 males and 2 females, of a mean
      +/-SE age of 51.1+/-1.7 years. Compared with the follow-up PSG, the initial PSG
      revealed significant increases in arousal index, spontaneous arousal index, wake
      time, and REM latency and significant reductions in sleep efficiency and REM
      sleep. CONCLUSIONS: Patients with AMI have altered sleep architecture, despite
      controlling for common sleep-disrupting environmental factors. Future research
      should explore other possible etiologies of sleep disruption in patients with
      AMI, including the underlying infarction itself and its associated physiological
      and inflammatory changes.

PMID- 16572053
TI  - Serum prolactin level in patients with multiple sclerosis: a case control study.
AB  - BACKGROUND: Multiple sclerosis (MS) is the most common demyelinating disorder of
      the central nervous system and is considered to be multifactorial with an
      autoimmune component. Prolactin (PRL) is a neuroendocrine peptide with potent
      immunomodulatory properties. Hyperprolactinemia enhances several autoimmune
      disorders and may play a role in the pathogenesis of MS. The aim of this study
      was to compare serum PRL levels in MS patients with those of healthy controls.
      MATERIAL/METHODS: There were 43 patients with definite MS and 43 sex- and age
      matched healthy controls. Conditions leading to a rise in PRL, such as pregnancy,
      lactation, and specific underlying diseases and drugs, were excluded. PRL levels
      were measured in fasting blood samples. For the MS group, disease duration and
      subtype, clinical manifestations, and expanded disability status scores (EDSS)
      were also recorded. RESULTS: There were no significant differences in serum PRL
      levels between the case and control groups in both women and men (376.78+/-231.11
      mIU/l in female patients with MS vs. 364.19+/-202.55 mIU/l in female controls,
      266.00+/-200.83 mIU/l in male patients with MS vs. 197.25+/-65.25 mIU/l in male
      controls). We also found no significant relationship between PRL and disease
      activity, disease duration, and EDSS. CONCLUSIONS: Our findings do not support
      the hypothesis that MS patients are in a hyperprolactinemic state. However,
      further studies in more homogenous MS subgroups are needed.

PMID- 16572052
TI  - Maternal age at delivery and order of birth are risk factors for type 1 diabetes
      mellitus in Upper Silesia, Poland.
AB  - BACKGROUND: Parental age and birth order as risk factors for childhood type 1
      diabetes mellitus were investigated using data from the Regional Diabetic Center
      for Upper Silesia, Poland, in a population-based study of 398 children with type
      1 DM aged 0-14 years born between 1979-1996. MATERIAL/METHODS: Noting differences
      in the proportions of children of different birth order between cases and
      controls, the data were stratified by birth order. For each stratum, odds ratios
      and their 95% confidence intervals were calculated to assess risks related to the
      mother's age. The homogeneity of the odds ratios related to the mother's age
      between strata was evaluated by the Mantel-Haenszel method. Risks related to
      mother's age and birth order were also estimated jointly by multivariable
      logistic regression. RESULTS: Decreased risk in later children compared with
      firstborns was noted. Increased maternal age was found to be a risk factor for
      type 1 DM. An increase in the mother's age by one year increases the risk of the
      child being affected by type 1 DM 1.07 times, and children born as the nth in the
      family are 1.59 times less exposed to the same risk than those born as the (n
      1)th. CONCLUSIONS: Children of different birth order have different risks of
      being affected by type 1 DM. Increased maternal age at the time of delivery is a
      risk factor for type 1 DM in Upper Silesia, Poland. To avoid bias in estimating
      risks, the mother's age and child's sequence number should be analyzed jointly.

PMID- 16572054
TI  - Possible association between circulating vascular endothelial growth factor and
      oxidative stress markers in hemodialysis patients.
AB  - BACKGROUND: Vascular endothelial growth factor is involved in the process of
      atherogenesis. Increased oxidative stress has been reported in hemodialyzed
      patients, but its influence on vascular endothelial growth factor levels remains
      unknown. MATERIAL/METHODS: The levels of two oxidative stress markers, Cu/Zn
      superoxide dismutase and autoantibodies against oxidized LDL, and the level of
      vascular endothelial growth factor were measured in pre-dialysis samples of
      hemodialyzed patients with and without cardiovascular disease and in healthy
      controls. RESULTS: Vascular endothelial growth factor levels were significantly
      increased in both hemodialysis groups compared with controls (all p < 0.001),
      more so in patients with than those without cardiovascular disease (p < 0.05).
      Cu/Zn superoxide dismutase levels were elevated in both patient groups (all p <
      0.001), whereas the levels of autoantibodies against oxidized LDL were increased
      only in the patients with cardiovascular disease (p < 0.05) compared with the
      controls. Vascular endothelial growth factor level positively correlated with
      Cu/Zn superoxide dismutase level (p < 0.01) and with the levels of autoantibodies
      against oxidized LDL (p < 0.05) in the whole hemodialysis group. CONCLUSIONS: Our
      data indicate for the first time a relationship between oxidative stress and VEGF
      levels in hemodialyzed patients, particularly in those with cardiovascular
      disease. This association may represent one of the mechanisms involved in the
      progression of atherosclerosis in this population.

PMID- 16572055
TI  - Psoriatic onycho-pachydermo-periostitis successfully treated with low-dose
      methotrexate.
AB  - BACKGROUND: Psoriatic onycho-pachydermo-periostitis (POPP) is a rare
      manifestation of psoriatic arthritis that is often misdiagnosed as a nail
      infection. The treatment for POPP has not yet been established. CASE REPORT: We
      present a case of a 67-year-old man who had no psoriatic skin lesions with POPP,
      characterized by psoriatic nail changes, painful swelling of the distal soft
      tissues on the great toes and fingers, and enthesopathies of the involved
      terminal phalanges. The clinical nail and arthritic changes were improved with
      methotrexate treatment 4 mg weekly for 6 months. CONCLUSIONS: Methotrexate can be
      recommended as the first-choice therapeutic agent for patients with POPP.

PMID- 16572056
TI  - Spontaneous perforation of the common bile duct with eosinophilia in an 18-month
      old girl: a case report and review of literature.
AB  - BACKGROUND: Spontaneous perforation of the common bile duct is a rare but
      important cause of jaundice in infancy, requiring prompt diagnosis and surgical
      intervention. First described in 1932, fewer than 150 cases have been reported to
      date. CASE REPORT: The report concerns a 18-month-old girl who developed mild
      jaundice, abdominal distension, and constipation three days prior to admission.
      On admission, ascites and hepatomegaly were detected and the complete blood count
      was normal, but on the 3rd, 4th, and 5th days of admission, the blood cell count
      revealed elevation of the eosinophil count to 16% of total WBC. Abdominal
      sonography showed a moderate amount of ascitic fluid and paracentesis
      demonstrated biliary ascites. Hepatobiliary scintigraphy suggested leakage of
      bile to the abdominal cavity. Exploratory laparotomy revealed clear bilious
      ascitic fluid and a ruptured common bile duct at the anterior wall of the
      junction of the cystic duct and the common bile duct. Three days after T-tube
      insertion and closure of the perforation, the eosinophil count returned normal.
      CONCLUSIONS: Perforation of the bile duct may be considered as one of the
      differential diagnoses of eosinophilia. This point makes our case a unique study,
      worthy of being reported.

PMID- 16572057
TI  - Atypical compound nevus arising in mature cystic ovarian teratoma.
AB  - BACKGROUND: Mature cystic ovarian teratoma (MCOT) is the most common primary
      ovarian tumor. Rarely, MCOT may undergo malignant transformation. Melanoma
      arising primarily in MCOT is a rare event. Melanocytic nevi have also rarely been
      reported in MCOT. CASE REPORT: A 28 year-old female presented with a palpable,
      4.6 cm, right pelvic mass on physical examination. Histologically, the cystic
      neoplasm demonstrated epidermis with numerous pilosebaceous units and respiratory
      type epithelium (endoderm) surrounded by adipose tissue and cartilage (mesoderm).
      A 2.0 x 1.0 cm pigmented area corresponded to a nevus with architectural and
      cytologic features of the so-called "dysplastic nevus," including variable-sized
      nests of nevomelanocytes irregularly distributed on distorted rete ridges,
      bridging of nests between rete ridges, fibroplasia around rete ridges, and
      junctional shouldering beyond the dermal nevus. The nevomelanocytes demonstrated
      moderate cytologic atypia. Diagnostic criteria of melanoma were not identified.
      CONCLUSIONS: Herein, we report, to the best of our knowledge, the first case of
      an atypical ("dysplastic") nevus, arising in a MCOT. No features of melanoma were
      present and the patient is disease-free at one-year follow-up. Rarely,
      melanocytic nevi and melanomas arise from the ectodermal component of MCOTs.
      Moreover, melanomas may arise de novo or in association with a nevus. Distinction
      between a melanocytic nevus, as in our case, and a primary melanoma is critical
      for determining the patient's prognosis and need for additional therapy. As
      primary ovarian melanomas, like their skin counterpart, may arise from a
      precursor lesion, removal of a melanocytic nevus, such as this atypical nevus,
      could theoretically prevent melanoma transformation.

PMID- 16572058
TI  - Using framing effects in medical education and training to meet community needs.

PMID- 16572060
TI  - Agreement between Mantoux skin testing and QuantiFERON-TB assay using dual
      mycobacterial antigens in current and former injection drug users.
AB  - BACKGROUND: Individuals infected with non-tuberculous mycobacteria may elicit
      false-positive reactions on tuberculin skin testing. The QuantiFERON-TB (QFT)
      assay utilizes tuberculin and M. avium antigens and, therefore, may be more
      specific for latent tuberculosis infection. The objective of this study was to
      investigate the agreement between the QFT and single and dual antigen skin
      testing for detecting latent M. tuberculosis and assess the impact of cross
      reactions from latent infection with other mycobacteria in inner-city injection
      drug users, a population at high risk for tuberculosis. MATERIAL/METHODS: We
      studied the agreement of results from skin testing using tuberculin and purified
      protein derivative-Battey (PPD-B) with the QFT test using tuberculin and
      Mycobacterium avium sensitin (MAS) in 48 HIV-seronegative injection drug users.
      RESULTS: The agreement between skin testing and the QFT assay for tuberculin was
      73% (kappa = 0.45) and for PPD-B/MAS was 63% (kappa = 0.12). Agreement between
      skin test tuberculin dominance (tuberculin reaction > or =5 mm greater than PPD
      B) and QFT tuberculin dominance (proportional difference between MAS and
      tuberculin reaction of > or =10%) was 75% (kappa = 0.53). All subjects tuberculin
      dominant by skin test were also QFT positive for tuberculin. Agreement between
      skin test Battey dominance and QFT avium dominance was 83% (kappa = 0.12).
      CONCLUSIONS: Results from the QFT assay and skin testing demonstrated moderate
      concordance in identifying subjects with latent tuberculous infection, and use of
      dual antigens did not appreciably improve the agreement between the two methods.

PMID- 16572061
TI  - Magnetization transfer imaging in chronic schizophrenia.
AB  - BACKGROUND: It has recently been suggested that new imaging methods such as
      magnetization transfer imaging (MTI) may play an important role in detecting
      subtle gray- and white-matter abnormalities in schizophrenia. The aim of the
      study was to investigate whether MTI, analyzed on a voxel-by-voxel basis, could
      identify areas of abnormal magnetization transfer ratio (MTR) in patients with
      schizophrenia. MATERIAL/METHODS: Twenty schizophrenic patients and 23 healthy
      controls matched for handedness and demographic variables underwent MTI and T1
      weighted structural MRI in a 3-tesla scanner. Post-processing was performed with
      SPM99 and included co-registration of the MT-weighted and non-MT-weighted images,
      calculation of the MTR maps, spatial normalization, and smoothing. Differences in
      the MTR maps between groups were assessed using two-sample t-tests. Significant
      changes in MTR were detected at an individual voxel threshold of p < 0.05.
      RESULTS: Group comparisons revealed no significant MTR changes, although there
      was a trend towards MTR reduction in the left superior temporal gyrus, in the
      right occipital cortex, and left periventricular white matter in patients
      compared with controls prior to correction for multiple comparisons (p < 0.001,
      uncorrected). CONCLUSIONS: MTI and voxel-by-voxel statistical analysis used in
      the study failed to identify regions of significant MTR reductions in
      schizophrenic patients. Our results disagree with findings of widespread MTR
      abnormalities reported in recent literature.

PMID- 16572062
TI  - Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated
      diarrhea: a prospective study.
AB  - BACKGROUND: Interest to probiotics for the prevention and treatment of antibiotic
      associated diarrhea is increasing gradually. The most promising seems to be
      Saccharomyces boulardii . Using a double-blind controlled study, we investigated
      the preventive effect of S. boulardii on the development of antibiotic-associated
      diarrhea in patients under antibiotherapy but not requiring intensive care
      therapy. MATERIAL/METHODS: All the patients were hospitalized at the Gulhane
      Military Medical Academy, Department of Infectious Diseases and Clinical
      Microbiology. S. boulardii was given twice daily during the course of antibiotic
      therapy and application was initiated in all patients as late as after 48 hours
      of antibiotic therapy. A total of 151 patients completed the study. RESULTS: The
      antibiotic-associated diarrhea development ratio in placebo group was 9% (7/78)
      and in the study group 1.4% (1/73) (p < 0.05). Stool samples from the patients
      with antibiotic-associated diarrhea were stored at -70 degrees C and Clostiridium
      difficile toxin A assay was performed using Enzyme Immune Assay as late as in
      seven days. C. difficile toxin A assay yielded positive results in two (2/7)
      stool samples from the patients with antibiotic-associated diarrhea in the
      placebo group and a negative result in the only patient who developed antibiotic
      associated diarrhea in the study group. CONCLUSIONS: The results implied that
      prophylactic use of Saccharomyces boulardii resulted in reduced, with no serious
      side effects, antibiotic-associated diarrhea in hospitalized patients.

PMID- 16572064
TI  - Derivation of embryonic stem cells for cellular therapy: challenges and new
      strategies.
AB  - Cellular therapy is the replacement of unhealthy or damaged cells or tissues by
      new ones. Embryonic stem (ES) cells are undifferentiated cells that can generate
      all the cell types of the body, and therefore hold the potential to cure a broad
      range of diseases and injuries, ranging from diabetes, liver and heart diseases,
      to neurological diseases, such as Alzheimer's and Parkinson's diseases. The
      derivation of human ES (hES) cells has been a major step toward bringing ES cell
      research to therapy. However, there are several challenges to the advent of ES
      cell research to therapy. Among them, the derivation of hES cell lines devoid of
      animal contaminants, the maintenance of their normal karyotypes, their potentials
      to form tumors upon grafting, and the derivation of isogenic hES cell lines.
      Stringent ethical and political guidelines are also limiting the use of human
      embryos for research, thereby limiting progress in ES cell research. Recently,
      several investigators have devised protocols to derive hES cells free of feeder
      layer and animal serum, reported that some established cell lines remain stable
      overtime, pre-differentiated ES cells in vitro to circumvent the risk of tumor
      formation, and derived ES cell lines without destroying embryos. In this
      manuscript, we will review and discuss these developments that may unlock ES cell
      research and therapy.

PMID- 16572063
TI  - RNAi: a novel antisense technology and its therapeutic potential.
AB  - Antisense oligonucleotide agents induce the inhibition of target gene expression
      in a sequence-specific manner by exploiting the ability of oligonucleotides to
      bind to target RNAs via Watson-Crick hybridization. Once bound, the antisense
      agent either disables or induces the degradation of the target RNA. This
      technology may be used for therapeutic purposes, functional genomics, and target
      validation. There are three major categories of gene-silencing molecules: (1)
      antisense oligonucleotide derivatives that, depending on their type, recruit
      RNase H to cleave the target mRNA or inhibit translation by steric hindrance; (2)
      ribozymes and deoxyribozymes--catalytically active oligonucleotides that cause
      RNA cleavage; (3) small interfering double-stranded RNA molecules that induce RNA
      degradation through a natural gene-silencing pathway called RNA interference
      (RNAi). RNAi is the latest addition to the family of antisense technologies and
      has rapidly become the most widely used approach for gene knockdown because of
      its potency. In this mini-review, we introduce the RNAi effect, briefly compare
      it with existing antisense technologies, and discuss its therapeutic potential,
      focusing on recent animal studies and ongoing clinical trials. RNAi may provide
      new therapeutics for treating viral infections, neurodegenerative diseases,
      septic shock, macular degeneration, cancer, and other illnesses, although in vivo
      delivery of small interfering RNAs remains a significant obstacle.

PMID- 16572066
TI  - Cell transplantation for cardiac repair.

PMID- 16572065
TI  - The effect of seasonal changes on blood pressure and urine specific gravity in
      children living in Mediterranean climate.
AB  - BACKGROUND: We aimed to evaluate the effects of seasonal changes on urinary
      specific gravity, blood pressure and urinary erythrocyte number in children
      living in Mediterranean climate. MATERIAL/METHODS: The study was conducted on 547
      children who presented for routine follow up to healthy-child care department
      between January 1997 and December 2002. Age, sex, weight, height, blood pressure,
      urinary specific gravity and urinary erythrocyte number were recorded by
      retrospective evaluation of files. Then, the parameters during summer were
      compared with those during winter. Additionally, correlation between the blood
      pressure, urinary specific gravity and urinary erythrocyte number was assessed
      separately during summer and winter. RESULTS: Anthropometrical measurements and
      mean age of the patients in summer and winter groups were similar. There was no
      significant change in urinary specific gravity (p > 0,05), while systolic and
      diastolic blood pressures were significantly higher in winter (p = 0.031 and p =
      0.028 respectively). Temperature and humidity levels did not change significantly
      among different years but mean air temperatures during summer positively
      correlated with time from 1997 till 2002 (r = 0.965, p = 0.002). Blood pressure
      and urinary specific gravity were not correlated to each other at any time.
      Contrarily, there was a positive correlation between urinary specific gravity and
      erythrocyte number in summer (p = 0.01). The number of children with hematuria
      and degree of hematuria did not differ significantly between summer and winter.
      CONCLUSIONS: Seasonal changes in Mediterranean climate do not lead to changes in
      hydration status or in urinary erythrocyte number in children. Therefore, the
      decrease in blood pressure during summer can not be attributed to the hydration
      status.

PMID- 16572067
TI  - Present status of clinical proteomic analysis for the early detection and
      determination of therapeutic strategy in lung cancer.
AB  - Although human DNA sequences have already been successfully decoded, there is
      still much we do not understand about the pathogenesis of human diseases.
      Proteomic analysis is comprehensive analysis of proteins, and there is a high
      probability that recent advances in this field will enable its application to
      individualized therapy based on thorough understanding of the pathogenesis of
      human diseases. Two-dimensional polyacrylamide gel electrophoresis (2-DE) and
      mass spectrometry (MS) are indispensable tools for proteomic analysis, and these
      technologies enable discovery of tiny changes of protein expression associated
      with pathogenesis. In this review we introduce the present status of proteomic
      analysis for cancer-related proteins, and especially lung cancer-related proteins
      in the attempt to discover new biomarkers for early detection and determine novel
      target-molecules for treatment. We believe that proteomic analysis will provide
      crucial information for diagnosis and treatment.

PMID- 16572068
TI  - Impact of lung preservation solutions, Euro-Collins vs. low-potassium dextran, on
      early graft function: a review of five clinical studies.
AB  - Currently, intracellular fluid type solutions that are prepared by modification
      of Euro-Collins solution (EC) have been the most commonly used by clinical lung
      transplant programs, which have been associated with a high rate of reperfusion
      injury. On the basis of the wealth of experimental data demonstrating the benefit
      of extracellular fluid type solutions over EC, one of the extracellular
      solutions, low-potassium dextran solution (LPD), became commercially available
      and has recently been applied to clinical settings. To date there have been 5
      clinical studies comparing the effect of EC with LPD on early lung graft
      function. This article reviewed these 5 reports to determine whether the
      beneficial effects of LPD, as observed in experimental settings, can also be
      identified in clinical lung preservation. Four studies were retrospective reviews
      and one was a prospective non-randomized study. Of these 5 studies, 3 studies
      demonstrated significantly improved recipient oxygenation in the LPD group
      compared with the EC group in the early post-operative period. In addition, a
      significantly shorter duration on mechanical ventilation in the LPD group was
      shown in 2 studies, and improved reperfusion scores or pulmonary compliance was
      shown in one study each. Four of 5 studies concluded that graft preservation with
      LPD leads to superior early graft function after lung transplantation. The impact
      of LPD on prolonged lung preservation and also on long term results of graft
      function will be a subject of future investigation.

PMID- 16572069
TI  - Preoperative prognostic factors for pN2 non-small cell lung cancer.
AB  - PURPOSE: The prognosis of non-small cell lung cancer (NSCLC) with pathologic
      mediastinal lymph node involvement (pN2) is poor in general. The majority of
      previously reported prognostic factors of pN2 disease are not available
      preoperatively. When we perform preoperative induction chemotherapy, we should
      undertake therapeutic planning according to preoperative factors. METHODS: We
      focused on preoperative clinicopathologic factors, and investigated the prognosis
      in 78 patients with pN2 NSCLC who received complete resection. RESULTS: Age,
      gender, histologic subtype, tumor location, smoking status and cT status were not
      related to patients' survival. On the other hand patients with cN0 disease and
      normal serum carcinoembryonic antigen (CEA) level had a significant favorable
      survival (p = 0.038 and p = 0.019, respectively). In addition, comorbidity had a
      significant survival impact (p = 0.031). Despite there being no independent
      prognostic factors by multivariate analysis, the patients without all of cN1-2
      disease, elevated serum CEA level and comorbidity had a significant favorable
      prognosis (p = 0.008). CONCLUSION: Among the preoperative factors examined, pN2
      patients with all cN0 disease, normal serum CEA level and no comorbidities might
      have a favorable prognosis. Combined use of these might be a useful prognostic
      determinant, and even in the presence of pN2 disease, patients without these
      unfavorable 3 factors might have a favorable prognosis when treated with surgery
      alone.

PMID- 16572070
TI  - Can the outcome of pediatric extracorporeal membrane oxygenation after cardiac
      surgery be predicted?
AB  - PURPOSE: The purpose of this study is to assess whether clinical and biochemical
      variables may be used to predict outcome in children treated with extracorporeal
      membrane oxygenation (ECMO) after cardiac surgery and to determine when to
      discontinue ECMO support. METHODS: We retrospectively reviewed the medical
      records of 26 children treated with ECMO after cardiac surgery at our institution
      from October 2000 to May 2004. RESULTS: Patients mean age was 16.4 months (range,
      two weeks to 144 months) and mean weight was 6.3 kg (range, 2.2-26 kg). Of the 26
      children requiring ECMO support, 23 underwent biventricular repair, and 3 had
      single ventricle procedure. None of the single ventricle repair or the truncus
      arteriosus repair group survived the ECMO support. Twelve patients (46%) survived
      the ECMO support and were discharged from hospital. Four patients needed ECMO
      support after 45 min (mean) of cardiopulmonary resuscitation (CPR) time (range =
      30-55 min) with 2/4 survived to discharge. All patients who survived to discharge
      showed no evidence of neurological deficit or disseminated intravascular
      coagulopathy (DIC) whereas 5 patients died following stroke, and 8 following DIC,
      respectively (p = 0.021 and 0.002). Renal failure developed in 8 cases (1
      survivor and 7 nonsurvivors, p = 0.022). Seventeen patients (65%) required re
      exploration of the mediastinum for bleeding. Length of time on ECMO, although it
      was longer among the nonsurvivors, was not significantly different between the
      survivor (74.5 hours) and nonsurvivor (118.2 hours) groups (p = 0.41). Inotrope
      score at ECMO initiation and serum lactate within 72 hours of ECMO were
      calculated and the difference between the two groups was not significantly
      related to survival (p = 0.29 and 0.22 respectively). CONCLUSION: Our findings
      suggest patients who develop renal failure, stroke and DIC during ECMO support
      have a high mortality. Patients with single ventricle physiology, and repaired
      truncus arteriosus may benefit less from ECMO support and have an increased risk
      of death. Elevated levels of lactate during the first 72 hours, high inotrope
      score at the initiation of ECMO and long ECMO support duration (more than 3 days)
      are all potential variables that can be used in determining when to discontinue
      ECMO support.

PMID- 16572071
TI  - Outcome of emergency conventional coronary surgery for acute coronary syndrome
      due to left main coronary disease.
AB  - BACKGROUND: Outcomes of emergency coronary artery bypass grafting (CABG) for
      acute coronary syndrome (ACS) due to left main coronary (LMT) disease remain
      unclear. This study aimed to assess prognoses for patients undergoing emergency
      CABG for ACS due to LMT disease. METHODS: One hundred and four patients
      undergoing emergency CABG for ACS due to LMT disease were retrospectively
      reviewed. All patients had intra-aortic balloon pumping (IABP) support and
      underwent surgery within 48 hours after onset. We determined predictors for
      operative mortality and calculated cardiac event free, actuarial survival, and
      cumulative graft patency rates. RESULTS: We found that 9 patients (8.7%)
      developed pre-operative cardiogenic shock and 7 of them required percutaneous
      cardiopulmonary support (PCPS). Operative mortality affected 9 patients (8.7%).
      Cardiac event free rate and actuarial survival rate at 10 years were 80.7 and
      75.4%, respectively. Logistic regression analysis showed that pre-operative
      cardiogenic shock was the only predictor for operative mortality (p = 0.0146,
      odds 5.96). Cumulative graft patency rates for internal thoracic artery and
      saphenous vein (SVG) at 5 years were 92.6 and 72.4%, respectively. One year-graft
      patency rate for the radial artery (RA) was 100%. CONCLUSION: It is still very
      hard to treat patients with cardiogenic shock. We suggest that immediate
      percutaneous coronary intervention (PCI) with mechanical supports is required
      prior to CABG for survival of patients with left main shock syndrome.

PMID- 16572072
TI  - Perioperative coronary artery spasm in off-pump coronary artery bypass grafting
      and its possible relation with perioperative hypomagnesemia.
AB  - PURPOSE: We experienced 3 cases of serious perioperative coronary artery spasm in
      off-pump coronary artery bypass grafting (OPCAB). In consideration of the causes,
      we directed our attention to hypomagnesemia, one of the triggers of coronary
      artery spasm. This study was performed to confirm the tendency to hypomagnesemia
      in OPCAB. METHODS: First, we report 3 patients having severe coronary artery
      spasm immediately after OPCAB with consideration of the causes. Second, serial
      magnesium (Mg) value (xylidyl blue method, normal 1.9-3.1 mg/dl) was measured in
      45 consecutive patients with OPCAB between April and October 2002, 1) before
      starting the operation, and 2) after the patient's entrance into the intensive
      care unit. RESULTS: Preoperative and postoperative values of Mg (mg/dl) were
      2.1+/-0.3, 1.7+/-0.3, respectively (p < 0.01). Postoperative incidence of
      hypomagnesemia was as high as 89% of the patients (40 out of 45 patients). In
      this study and thereafter, we corrected hypomagnesemia with magnesium sulfate
      during and after OPCAB, and no perioperative coronary artery spasm occurred.
      CONCLUSION: Hypomagnesemia, one of the triggers of coronary artery spasm, is very
      common in OPCAB. We strongly recommend the correction of hypomagnesemia during
      and after OPCAB for the prevention of perioperative coronary artery spasm.

PMID- 16572073
TI  - Experimental study on stability of a high-porosity expanded
      polytetrafluoroethylene graft in dogs.
AB  - PURPOSE: The purpose of the present study was to evaluate the stability of a high
      porosity expanded polytetrafluoroethylene (ePTFE) graft, which has been shown to
      possess excellent biocompatibility and tissue integration. METHODS: The graft
      used in the present study was a high-porosity ePTFE graft , which had an average
      internodal distance of approximately 60 microm and a random node architecture
      with tortuous path channels extending from the outer to the inner surface. Eleven
      beagle dogs (each group n = 3 or 4) weighing 10-12 kg were used. The graft, with
      a 6 mm inside diameter and a 30-40 mm length, was implanted into the canine
      abdominal aorta and retrieved after 2-80 weeks. The deformation of the graft was
      evaluated by conventional computed tomography (CT). The radial tensile strength,
      longitudinal tensile strength, and suture retention strength of the graft were
      measured after 2-80 weeks. RESULTS: CT studies showed no anastomotic aneurysm or
      deformation of the graft. Physical tests demonstrated no significant
      deterioration in suture retention strength, radial tensile strength or
      longitudinal tensile strength for periods ranging from 2-80 weeks compared to pre
      implantation grafts. CONCLUSION: The graft possesses adequate stability that
      ensures safe and effective clinical use.

PMID- 16572074
TI  - Midterm results of transluminal endovascular grafting in patients with DeBakey
      type III dissecting aortic aneurysms.
AB  - OBJECTIVE: Transluminal endovascular grafting (TEG) is less invasive than
      conventional operative procedures for the treatment of DeBakey type III
      dissecting aortic aneurysms (DAA). We have used two different kinds of stent
      grafts covered with woven Dacron grafts, a Gianturco Z-stent graft (G-SG) and a
      Spiral Z-stent graft (S-SG). Because the G-SG lacks adequate flexibility, the end
      of the graft may injure the intima after long-term deployment in the proximal
      descending aorta. We have used S-SGs, which are more flexible than G-SG, to
      improve outcome. We report our late midterm results and discuss treatment policy.
      SUBJECTS AND METHODS: We studied 45 patients with DeBakey type III DAA. Thirty
      two G-SGs and 13 S-SGs were used. Follow-up ranged from 1 year 6 months to 8
      years 5 months (mean, 5 years 2 months). RESULTS: 1) Surgical outcome: (a) TEG
      was technically successful in all patients. There was no operative mortality. (b)
      One week after surgery, 36 patients had no endoleaks, 5 had minor endoleaks, and
      4 had major endoleaks. 2) Late midterm results: (a) Four patients with residual
      major endoleaks, underwent replacement of the descending thoracic aorta. (b)
      Intimal injury occurred at the distal end of the stent graft 4 to 18 months
      (mean, 10.5 months) after surgery in 12 patients with G-SG and 1 with S-SG. One
      of these patients had recurrent dissection, and 12 had ulcer like projections
      (ULP). Two patients underwent additional stent implantation to block blood flow.
      (c) Four patients with S-SG had major endoleaks 3 to 6 months after surgery. In 3
      of these patients, the Spiral Z-stents were compressed and occluded, and thrombus
      had formed in the lumen. Three patients underwent replacement of the descending
      thoracic aorta. (d) Additional replacement of the descending thoracic aorta was
      done in 9 of the 45 patients (20%) 4 to 24 months after TEG. All patients
      responded to treatment and were discharged from the hospital. CONCLUSION: Intimal
      injury was caused by Gianturco Z-stents because of inadequate flexibility, and
      endoleaks and stent-graft occlusion were caused by Spiral Z-stents because of
      insufficient radial force against the aortic wall. The development of stents with
      these improved properties is expected to further improve outcome.

PMID- 16572075
TI  - Ultraflex expandable stents for the management of air leaks.
AB  - Postoperative empyema and aspergillosis were diagnosed in a 66-year-old man.
      Since non-operative therapy was not effective, we performed surgery. On the 8th
      postoperative day, a covered Ultraflex expandable stent (Boston Scientific,
      Galway, Ireland) was implanted to make a one-way airway for blocking a major air
      leak from a bronchopleural fistula causing respiratory distress. His general
      condition improved gradually, and he was discharged 30 days after stenting. In
      conclusion, we used a covered Ultraflex expandable stent to make an airway to
      block an air leak. This may be a new application for this stent.

PMID- 16572076
TI  - Coexistent lung carcinoma and active pulmonary tuberculosis in the same lobe.
AB  - We observed a rare case of lung carcinoma accompanied by active pulmonary
      tuberculosis in the same lobe. The chest x-ray of a 49-year-old man revealed an
      abnormal shadow in the right upper field and a giant bulla in the left upper
      field. Chest computed tomography (CT) revealed a nodule with consolidation, which
      was not continuous in the right S3. Bronchoscopically, epidermoid carcinoma
      existed in the proximal right upper bronchus. In the sputum specimens, the smear
      was negative, but the polymerase chain reaction of Mycobacterium tuberculosis and
      culture was positive. Anti-tuberculosis treatments were administered for
      approximately 4 weeks, but the chest x-ray remained unchanged. Right upper
      lobectomy with bronchoplasty (wedge resection of the right upper bronchus) was
      performed, and the anastomosis was covered with an intercostal muscle flap.
      Lymphadenectomy of the right hilum and mediastum was also performed. Microscopy
      revealed epidermoid carcinoma in the proximal tumor (pT3N0M0-stage IIB) and
      epithelioid granuloma with caseous necrosis, granulomatous pneumonia, exudative
      lesions, and fibrocaseous nodules in the distal lung. After surgery, anti
      tuberculosis treatment was resumed.

PMID- 16572077
TI  - Rupture of a large cell neuroendocrine carcinoma, causing early local recurrence.
AB  - We present a case of large cell neuroendocrine carcinoma (LCNEC) requiring an
      urgent operation due to a rupture-induced shock. Primary lung cancers rarely
      rupture. This event could have spread malignant cells. Our patient died of
      pleural dissemination at day 81 after the operation. We had difficulty diagnosing
      the lesion before rupture despite various examinations including biopsy. In cases
      of a large, growing, cavitating mass, we should consider the possibility of
      malignant tumor, and a surgical approach to prevent rupture. A ruptured malignant
      tumor may also be treated by adjuvant therapy rather than resection.

PMID- 16572078
TI  - Surgical experience of subacute pulmonary thromboembolism with severe pulmonary
      hypertension.
AB  - Surgical treatment for subacute pulmonary arterial thromboembolism has previously
      been considered to be inappropriate. We undertook a pulmonary arterial
      thrombectomy and removal of a floating right heart thrombus in a patient who had
      been symptomatic for over a month. The pulmonary arterial pressure, which had
      been equal to the systemic pressure preoperatively, decreased gradually and
      almost normalized one month postoperatively. Pulmonary perfusion scintigraphy
      revealed a dramatic improvement and the patient returned to normal life
      activities.

PMID- 16572079
TI  - Lobar torsion after pulmonary resection; report of two cases.
AB  - Lobar torsion is a rare complication after pulmonary resection. We report a case
      of right middle lobe torsion following a right upper lobectomy, and left lower
      lobe torsion following a left upper lobectomy. Careful postoperative clinical
      observation, chest radiography, fiberoptic bronchoscopy (FOB), and computed
      tomography (CT) are crucial for precise diagnosis of lobar torsion following
      pulmonary resection. Both patients underwent re-thoracotomy; a middle lobectomy
      and completion pneumonectomy were performed. In the clinical management of lobar
      torsion urgent diagnosis and conclusive surgical resection is needed to avoid
      mortality and morbidity.

PMID- 16572080
TI  - A successfully operated case of prosthetic valve thrombosis during planned
      pregnancy.
AB  - The patient was a 29-year-old woman who, when she was an 8-year-old, had
      undergone atrial septal defect (ASD) closure and mitral valve replacement (MVR)
      using a Bjork-Shiley valve (25 mm) for Lutembacher syndrome. Because of a planned
      pregnancy, warfarin had been replaced by heparin. During the 7th week of
      pregnancy, she was admitted to our hospital because of dyspnea. She was diagnosed
      with acute heart failure due to prosthetic valve thrombosis. Following
      termination of pregnancy, the mitral valve was replaced with an ATS valve (25
      mm). She was discharged 10 days after surgery without complications.

PMID- 16572081
TI  - Temporary axillo-femoral bypass for abdominal aortic aneurysm repair in high risk
      patients.
AB  - Abdominal aortic aneurysm (AAA) is sometimes associated with coronary artery and
      valvular disease. We report the successful treatment of a 76-year-old woman
      diagnosed with an infrarenal AAA, associated with severe mitral regurgitation and
      double-vessel coronary artery disease. First, AAA repair, using temporary axillo
      femoral bypasses on both sides was done. Second, after 77 days, we simultaneously
      undertook coronary artery bypass grafting (CABG) and mitral valve repair. This
      staged operation achieved an excellent result. This rarely used abdominal aortic
      surgical procedure contributed to minimizing variations in afterload, an
      important consideration in high risk cardiac patients.

PMID- 16572082
TI  - Traumatic pseudoaneurysm of the subclavian artery following anterior dislocation
      of the shoulder: a report of a surgical case.
AB  - Vascular complications associated with simple anterior dislocation of the
      shoulder joint are rare. We report on a patient with a pseudoaneurysm of the
      right subclavian artery following anterior dislocation of the right shoulder.
      Complaints of progressive neurological deficit and swelling in the right upper
      extremity were initially attributed to hemarthrosis of the right shoulder joint,
      but pseudoaneurysm of the right subclavian artery was identified during an
      emergent operation on the right shoulder. Uncontrollable arterial hemorrhaging
      from the skin incision erupted during the operation and was treated using a
      double surgical approach.

PMID- 16572083
TI  - Current status of carotid artery stent placement.

PMID- 16572084
TI  - Review of stents for the carotid artery.
AB  - The individual characteristics of a stent may make it an attractive choice in
      some circumstances, but render it a less desirable option in others. The
      applicability depends primarily on the arterial anatomy and the specific details
      of the lesion being treated. A careful assessment by the interventionalist is
      required to select the proper type of stent that is of appropriate size.
      Certainly, personal preferences and familiarity with a specific device may
      legitimately influence the decision to choose one stent over another. Finally,
      stent design can play a role in the selection procedure. Although carotid stents
      are often functionally equivalent in the clinical setting and have been used
      successfully to treat a wide variety of lesions, a basic knowledge of stent
      geometry can contribute to make up your mind in certain carotid cases.

PMID- 16572085
TI  - The carotid atherosclerotic plaque and microembolisation during carotid stenting.
AB  - Microembolisation is an important issue in carotid artery stenting. During
      different phases in the stenting process, numerous emboli are dislodged from the
      atherosclerotic plaque. Embolisation can be measured as microembolic signals
      detected by transcranial Doppler (TCD) monitoring during the procedure or as new
      ischemic areas determined by magnetic resonance imaging. This article gives an
      overview of the principles of emboli detection methods, their clinical relevance,
      and risk factors associated with microembolisation. In addition, protection
      devices are discussed in relation to embolisation. Although they potentially
      protect the brain, particularly filter devices increase the amount of TCD
      detected cerebral microemboli. Special attention is paid to the carotid artery
      plaque, which is subject to ongoing research that may yield important
      implications for clinical practice in the near future. Evidence is accumulating
      that unstable, vulnerable plaques are associated with increased microembolisation
      during carotid interventions. This knowledge of the vulnerable plaque can be
      translated to the clinical setting by plaque imaging. A first approach has been
      made by duplex imaging of carotid plaque morphology. More advanced methods such
      as molecular magnetic resonance imaging and optical coherence tomography could
      aid in optimal treatment selection based on plaque characteristics thus reducing
      microembolisation and associated cerebral adverse events.

PMID- 16572086
TI  - Is there any evidence that cerebral protection is beneficial? Experimental data.
AB  - This article presents the available experimental data from the world literature
      on the use of cerebral protection devices during carotid artery stenting (CAS).
      Clinical studies relying on surrogate markers of cerebral embolisation in place
      of neurological event rate as primary outcome measures are evaluated alongside
      bench-top and animal studies. These surrogate markers include evaluations of
      outcomes using procedural transcranial Doppler (TCD) and diffusion-weighted
      magnetic resonance imaging of brain (DWI). Pathological analyses of debris
      retrieved from in-vivo analyses of protection devices are also included in this
      review because although the focus of these studies was primarily clinical, the
      laboratory data will be preferentially presented and it provides interesting
      insights. It can be shown that each of the three philosophies of cerebral
      protection, namely flow arrest (proximal or distal), flow reversal and distal
      filtration is capable of the entrapment of sizeable debris that would logically
      threaten devastating stroke if it embolized to the brain. Whilst balloon
      occlusion significantly reduces the procedural microembolic load (particles less
      than 60 mm) and flow reversal may be the first means to entirely eliminate it,
      filters may be associated with increased microembolization. This has been
      described by some workers as controlled embolization. Certainly, particles
      smaller than the pore size of currently available filters (60-140 mm) will
      readily evade capture due to filter periflow and through-flow. There is evidence
      to suggest that tens of thousands of particles of this size may be released
      during CAS and there is some evidence that this may be associated with more new
      white lesions on DWI of brain. The clinical consequences of this controlled
      embolization however, remain unclear and sophisticated neuropsychometric test
      batteries may need to be applied at later time points to detect subtle injury
      that may be compounded by a late inflammatory response around cerebral emboli.
      Devices relying on placement in the distal internal carotid artery (ICA) for
      establishment of protection risk intimal damage and the release of microemboli
      due largely to device deployment and retrieval. Although devices effecting flow
      arrest and flow reversal will limit all embolization, they do so at the expense
      of constant procedural cerebral perfusion and may not be tolerated in patients
      with precarious cerebral reserve capacity, loss of integrity of the Circle of
      Willis and/or high-grade stenosis of the contralateral ICA. Advances in the
      concept of cerebral protection will require technical refinements to existing
      devices, alternative mechanical strategies and/or pharmacological plaque
      stabilization.

PMID- 16572088
TI  - Can carotid stenting registries help in determining predictors of neurological
      outcome?
AB  - AIM: Carotid stenting (CS) has proved to be a safe alternative to carotid
      endarterectomy, and subsets of patients who may benefit from carotid stents
      rather than surgery still need to be defined. Randomized trials and individual
      series are looking at predicting factors of early outcome after carotid
      angioplasty and stenting (CAS) that can hardly be applied to all series. We
      analyzed early results of the Eurocast registry and discussed the potential role
      of multicentric registries in determining such outcome predictors. METHODS: The
      Eurocast registry is an online prospective registry on CAS that collected 897
      procedures from February 2000 to December 2005 across 20 centers. Statistical
      analyses were performed with the univariate Fisher's exact test on CS procedures,
      excluding sole balloon angioplasty. Risk factors reported were hypertension,
      hyperlipidemia, past or current history of smoking, diabetes mellitus, obesity,
      cardiac disease, other vascular disease, pulmonary disease, hostile neck and
      renal failure. Half of patients (50.2%) had symptomatic carotid lesions. Local
      anesthesia (91.8%) and retrograde femoral access (95.6%) were the preferred
      method. Overall procedures were achieved in 98.2%, of which 84.5% were performed
      under cerebral protection. RESULTS: Intraoperative neurological complications
      occurred in 26 (3.1%) of 824 procedures achieved. No immediate deaths were
      reported. The intraoperative ipsilateral stroke/death rate was 1.7%. The overall
      in-hospital stroke/death rate was 3.5%. Significant predictors of early
      neurological complications were infarctions on preoperative cerebral CT scanning,
      a deficient circle of Willis, a too short preoperative length of medication (7
      days or less), any additional intervention (stenting and/or balloon dilatation),
      bradycardia and hypotension. Less reliable predictors were: age >70 years, renal
      failure, preoperative speech or motor deficit, postradiation stenosis, lesion on
      the left carotid axis and lesion on the common carotid artery. CONCLUSIONS: This
      analysis confirmed that CS is a feasible and secure technique to treat carotid
      stenosis. However, the determination of neurological outcome predictors remains
      subject to further confirmation. Other patient subgroups identified in other
      studies (female sex, diabetics, coronary disease) should be investigated more
      precisely. Finally, the Eurocast analysis showed that the setting up of risk
      scores would be dependent on local practices, physicians' experience and would
      not be reproducible.

PMID- 16572087
TI  - Is there evidence that cerebral protection is beneficial? Clinical data.
AB  - Advances in angioplasty techniques and the development of low-profile, flexible,
      tapered nitinol stents designed specifically for carotid applications have made
      carotid artery stenting a viable alternative to carotid endarterectomy for
      treatment of occlusive disease of the carotid arteries. During the stenting
      process, however, debris may be released and cause distal embolization that can
      lead to stroke or death. Thus, several embolic protection devices have been
      developed for use in carotid stenting, two of which are available in the United
      States. In the past 5 years, data from several large trials, series, and
      registries of carotid artery stenting-reflecting the experience in thousands of
      patients-have become available. These investigations include the CAVATAS study,
      the Global Carotid Artery Stent Registry, the SAPPHIRE study, the ARCHeR trials,
      the CABERNET registry, the BEACH registry, the SECuRITY registry, the German
      Registry, and the EVA-3S trial. The studies have provided considerable evidence
      that use of an embolic protection device decreases the incidence of cerebral
      embolic events during carotid stenting in both symptomatic and asymptomatic
      patients. They have also shown that increased experience with angioplasty in the
      carotid artery decreases complication rates associated with the procedure, even
      when a protection device is not employed. Although the benefits of routine use of
      cerebral protection have not been confirmed by level 1 evidence, a consensus
      supports such use.

PMID- 16572089
TI  - Management of carotid restenosis.
AB  - Carotid endarterectomy is the preferred method for cerebral revascularization in
      patients with symptomatic and asymptomatic high-grade extracranial carotid artery
      stenosis. Carotid artery stenting has recently emerged as a less invasive
      alternative to endarterectomy. Carotid stenting has been demonstrated to be
      technically feasible and safe in high-risk patients with current data indicating
      clinical equipoise with respect to endarterectomy. It is clear that carotid
      stenting will continue to be performed at increasing rates after these
      encouraging outcomes. Therefore, it is anticipated that there will be a
      corresponding increase in the number of in-stent restenosis cases. Considerable
      controversy exists regarding the clinical significance, natural history,
      threshold for management, and appropriate intervention of recurrent carotid
      stenosis after endarterectomy and after stenting. This review analyses current
      information on this important clinical problem and presents evidence-based
      recommendations for the diagnosis and management of recurrent carotid stenosis.

PMID- 16572090
TI  - The use of a surgical sealant (CoSeal) in cardiac and vascular reconstructive
      surgery: an economic analysis.
AB  - AIM: We designed a study to estimate the economic impact of CoSeal Surgical
      Sealant for the prevention of anastomotic bleeding in cardiac and vascular
      surgery. We also explored the potential economic value of CoSeal as a means of
      inhibiting the formation of pericardial tissue adhesions. METHODS: A Delphi panel
      of 6 expert vascular and cardiac surgeons provided the assumptions and estimates
      needed to develop a decision analysis model to assess the impact of sealant on
      the costs associated with low- and high-risk forms of cardiac (valve
      replacement/reconstruction) and vascular (abdominal aortic aneurysm [AAA] repair,
      femoral bypass grafting) surgery. The primary outcome was incremental cost per
      patient. RESULTS: For valve repair/replacement surgery, sealant was expected to
      confer cost-savings in high-risk but not low-risk procedures. Predicted cost
      savings for high-risk AAA repairs were substantial, but minimal in the overall
      AAA group. Cost-savings were predicted for sealant use in all femoral-popliteal
      ePTFE bypass grafts, but in high-risk femoral-femoral ePTFE bypass grafts only.
      CONCLUSIONS: According to our decision analysis model, routine use of surgical
      sealant in select subgroups may confer considerable economic benefits to health
      service budgets. Future research should aim at testing this model in a real-world
      hospital setting. Assessment of the value of CoSeal in the prevention of
      postsurgical adhesions showed that expert surgeons see a need for effective
      prophylaxis. Further research into the clinical and economic benefit of this
      intervention is required.

PMID- 16572091
TI  - Percutaneous transluminal angioplasty for treatment of ''below-the-knee''
      critical limb ischemia: early outcomes following the use of sirolimus-eluting
      stents.
AB  - AIM: We investigated the safety and efficacy of sirolimus-eluting stents in the
      treatment of patients with severe below-the-knee' critical limb ischemia.
      METHODS: Between October 2004 and January 2005 we performed 20 percutaneous
      transluminal angioplasty procedures on 18 patients (7 female, 11 male, mean age
      72.8 years), implanting 24 sirolimus-eluting stents. At pre-procedure, 12
      patients (66.7%) presented with a Rutherford Category 4, 4 (22.2%) with Category
      5 and 2 (11.1%) with Category 6. The majority of patients (72.2%, n=13) were non
      smokers and 77.8% (n=14) presented with hypercholesterolemia. Calcification was
      present in 52.2% (n=12) of lesions. Pre-dilation was performed in half the
      patients. The majority of lesions (95.7%, n=22) were treated with a single
      sirolimus-eluting stent. Two patients underwent 2 procedures, each one receiving
      2 sirolimus-eluting stents. Clinical examination and quantitative vascular
      analysis were performed in all patients at discharge and at 6-month follow-up.
      RESULTS: Percutaneous transluminal angioplasty was successfully performed on all
      18 patients. The mean stent length and stent diameter were 30.29 mm and 3.23 mm,
      respectively. Mean follow-up was 256 days (170-368 days). At the 6-month follow
      up, the minimum lumen diameter as measured by Quantitative Vessel Analysis was
      2.39 mm with an attendant LLS of 0.38 mm. The overall 6-month survival and limb
      salvage rate were 94.4% and 94%, respectively. CONCLUSIONS: Our results suggest
      that treatment with sirolimus-eluting stents can be considered as an effective
      and safe treatment of patients with critical ischemia.

PMID- 16572092
TI  - What is the value of available risk-scores in predicting postoperative
      complications after aorto-iliac surgery? A prospective non randomized study.
AB  - AIM: With an aging population, atherosclerotic manifestations are steadily
      increasing. Beside the anatomical and pathophysiological preoperative risk
      factors accompanying perioperative risk-factors like patient's age, length of
      operation, blood loss and skill of the surgeon, all need to be accounted for when
      assessing the risk of morbidity and mortality after vascular surgery. The demand
      for cost effectiveness may make a risk-score system useful. The aim of the
      present study was, therefore, to prospectively apply various scoring systems in
      order to estimate outcome in patients undergoing aortobifemoral surgery due to
      arterial occlusive disease at the aorto-iliac level. METHODS: A prospective non
      randomized study was carried out. The SPSS 9.0 statistical package for Windows
      and, for nominal data, chi-squared-tests were used to compare rates between
      groups. For continuous data analysis of variance (ANOVA) was performed. When
      appropriate, a multivariate analysis with binary-regression by Wald was used.
      Sensitivity and specificity was done using ROC-curves. P < 0.05 was considered
      significant. From May 1996 to June 2000, 107 patients were included in the study.
      Besides basic data, all postoperative complications were noted according to a
      specific definition. Four different risk-scoring systems were used: ASA
      classification; the acute physiology and chronic health evaluation (APACHE-II)
      system; the physiological and operative severity score for enumeration of
      mortality and morbidity (POSSUM) classification and, finally, the simplified
      acute physiology score (SAPS) classification. RESULTS: We found no significant
      correlation between risk-scores and outcome. None of the scoring systems used was
      able to predict mortality. The independent factors that influenced the
      postoperative complication rate were operating time, blood loss, intraoperative
      assisted ventilation time and age. The endpoint using the relative operating
      characteristic (ROC) curves analysis was either mortality or morbidity.
      CONCLUSIONS: It can be concluded that none of the systems analyzed separately was
      useful for determining morbidity and mortality. We still lack a system, that can
      be used preoperatively in an individual case and the vascular surgeon still has
      to build up his own clinical judgement or to transfer a clinical judgement.

PMID- 16572093
TI  - Combined surgical and endovascular treatment of extensive thoracic aortic
      aneurysm.
AB  - AIM: Patients with extensive aneurysm involving ascending aorta, aortic arch and
      descending aorta are usually treated by sequential operations. For these patients
      we can also use combined surgical and endovascular treatment. The experience with
      this procedure published in the literature is very limited. We report our
      experience in the ''elephant trunk'' technique followed by an endovascular stent
      grafting of the descending thoracic aorta in a small group of three consecutive
      patients with extensive thoracic aortic aneurysm. METHODS: Three consecutive
      patients with extensive thoracic aortic aneurysm or chronic dissection underwent
      combined surgical and endovascular treatment between January and December 2004.
      The procedure was carried out as a two-stage procedure. During the first stage
      aortic arch was replaced using the elephant-trunk'' method and during the second
      stage the stentgrafting of the descending aorta was performed. RESULTS: All three
      patients were treated successfully. There was no death, no endoleak and no
      permanent neurological deficit. One patient had a transient paraparesis. In all
      patients the spiral CT demonstrated excellent technical result without endoleak
      and with thrombosis of the paraprosthetic space. CONCLUSIONS: We can conclude,
      that the combined surgical and endovascular treatment of extensive thoracic
      aortic aneurysm is a feasible method which could reduce mortality and morbidity.
      In our institution the elephant trunk technique followed by an endovascular stent
      grafting of the descending aorta is the preferred method of treatment in patients
      with extensive thoracic aortic aneurysm involving ascending aorta, aortic arch
      and descending aorta.

PMID- 16572094
TI  - Elderly valve replacement with bioprostheses and mechanical prostheses.
      Comparison by composites of complications.
AB  - AIM: The goal of aortic valve replacement (AVR) surgery in the elderly (= or >75
      years) is to extend survival and minimize valve-related morbidity, mortality and
      reoperation. As the elderly population lives longer, those with implanted valves
      are at risk of suffering valve related complications. We hypothesize that
      bioprostheses are appropriate for the elderly. METHODS: The follow-up evaluation
      of 966 patients with valves (AVR, 666; mitral valve replacements [MVR], 226;
      multiple valve replacements [MR], 74) implanted between 1975 and 1999 was
      examined. There were 879 bioprotheses (BP) and 87 mechanical prostheses (MP). The
      mean age was 78.9+/-3.3 years (range 75-94.6 years). Concomitant coronary artery
      bypass was performed in AVR in 51.7%, MVR in 50.4% and MR in 28.4%. Valve type,
      valve lesion, coronary artery bypass (previous/concomitant), age and gender were
      considered as independent predictors of composites and survival. The total follow
      up was 3905 patient-years. RESULTS: Early mortality was for AVR 9.6% (64), MVR
      15.0% (34) and MR 25.7% (19). The late mortality was for AVR 8.8%, MVR 10.4% and
      MR 8.8%/patient-year. The only independent predictor of survival and valve
      related mortality, morbidity and reoperation was age for survival in those with
      AVR, hazard ratio 1.15 [CL 1.03-1.27] p=0.0094). The BP reoperative rate was
      0.5%/patient-year (reoperation was fatal in 6/15) of total, MP reoperative rate
      was 0% [reasons for reoperation structural valve deterioration (4), non
      structural dysfunction (6), prosthetic valve endocarditis (5), reoperation
      fatality due to non-structural dysfunction (2), prosthetic valve endocarditis
      (4)]. Overall patient survival at 10 and 15 years, respectively, was 30.5+/-2.4%
      and 3.6+/-2.2% irrespective of valve position and type. Overall actual and
      actuarial freedom from valve-related morbidity at 15 years was 96.8+/-0.9% and
      93.7+/-2.3%, respectively. Actual and actuarial overall freedom from valve
      related mortality at 15 years was 84.3+/-2.4% and 58.4+/-0.9%, respectively.
      Overall actual and actuarial freedom from valve related reoperation at 15 years
      was 95.8+/-1.6% and 74.8+/-16.9%, respectively. CONCLUSIONS: BP valves are
      further confirmed to be a good option for AVR in patients = or >75 years of age.

PMID- 16572095
TI  - Urgent/emergent surgical revascularization in unstable angina: influence of
      different type of conduits.
AB  - AIM: In patients with unstable angina (UA) undergoing nonelective myocardial
      revascularization we compare the outcomes of skeletonized bilateral internal
      mammary arteries (BIMA) vs left internal mammary artery (LIMA) and saphenous vein
      grafts (SVGs) vs SVGs only. METHODS: Between January 1997 and December 2003, 758
      patients: 612 (80.7%) males, mean age 62+/-12 years, underwent nonelective
      coronary artery bypass grafting (CABG) for unstable angina; 205 (27%) were
      operated emergently and 553 (73%) urgently. BIMA were employed in 320 (42%)
      patients (Group B) , isolated LIMA and/or SVGs in 332 (44%) patients (Group M)
      and only SVGs in 106 (14%) (Group S). RESULTS: In-hospital mortality (B=5.9%,
      M=4.5% and S=7.5%), and perioperative myocardial infarction (B=2.2%; M=1.9%,
      S=3.7%) were similar between the 3 groups (P=NS). Actuarial survival at 1, 3 and
      7 years was 98.7%, 97.5% and 96.2% in group B, 99.3%, 94.8% and 89.4% in group M
      (P< 0.057 at 7 years follow-up) and 98%, 93.2% and 84.3% in group S (P=0.001). At
      7 years follow-up, the event-free cardiac survival (92% vs 89.1%, P=0.045),
      angina-free survival (98.6% vs 95.8%, P=0.056), reoperation-free cardiac survival
      (98% vs 96%, P= 0.05) and infarct-free cardiac survival (98.7% vs 96.9%, P=0.062)
      showed a consistent trend to be superior in group B. Multivariate analysis
      identified age >65 years (P= 0.02), left ventricular ejection fraction (LVEF)
      <35% (P= 0.01), >1 ischemic irreversible area (P= 0.03) as independent predictors
      for late deaths, while the use of the LIMA (P= 0.006) and both mammary arteries
      (P= 0.001) decreased the risk of late deaths. CONCLUSIONS: The use of BIMA in
      nonelective CABG for UA is safe and effective. There is a trend, however, toward
      a survival benefit with improved freedom from late cardiac events (recurrence of
      angina, freedom from reoperation and infarction).

PMID- 16572096
TI  - Is hypothermia a benefit? Von Willebrand factor in pediatric cardiopulmonary
      bypass.
AB  - AIM: The use of cardiopulmonary bypass (CPB) is associated with the risk of
      development of postpump syndrome. Thrombocyte activation leads to microembolism,
      endothelial damage and necrosis with release of various substances, such as the
      von Willebrand factor (vWf). High levels of vWf increase the risk of
      postoperative complications and mortality. Our objective was to find a
      correlation between CPB and plasma levels of vWf in pediatric patients operated
      on for congenital heart defects. METHODS: Twenty patients with congenital heart
      defects (ventricular septal defect, atrial septal defect/partial anomalous
      pulmonary vein drainage, Bland White Garland syndrome) were operated on with the
      use of CPB. The arterial blood was sampled after induction of anesthesia, 5
      minutes after commencing CPB, 1 hour and 3 hours after surgery. The plasma levels
      of vWf were measured and compared to selected clinical findings. RESULTS: There
      was no early mortality. There were no significant differences in CPB and aortic
      cross clamp times when compared in patients with various defects. vWf plasma
      levels were significantly elevated in all patients 1 hour and 3 hours after
      surgery. We found no correlation between vWf levels and type of defect, CPB
      duration, aortic cross clamp as well as reperfusion time. However, we were able
      to demonstrate that the observed elevation of vWf levels was almost 4-fold higher
      in patients cooled down to lower temperatures (15 patients; mean rectal value
      27.64+/-0.7 degrees C) than in 5 patients (mean rectal temperature 30.74+/-1.56
      degrees C) where only slight elevation was found. There were no differences in
      the postoperative course of these patients. All patients were discharged from
      hospital 10+/-3 days after operation (mean value 9 days). CONCLUSIONS: vWf plasma
      levels are significantly elevated after pediatric hypothermic CPB. It seems that
      the augmentation of vWf values could be independently associated with rate of
      hypothermia.

PMID- 16572097
TI  - Successful perioperative utilisation of inhaled nitric oxide in mitral valve
      surgery.
AB  - Pulmonary hypertension associated with mitral valve disease can significantly
      complicate mitral valve replacement. Nitric oxide (NO) has an established role in
      congenital heart surgery and in cardiac transplantation. However the evidence to
      date suggests that iNO does not provide a clinical advantage in pulmonary
      hypertension associated with valvular heart disease. We discuss a 56-year-old
      male with acute mitral incompetence who underwent emergency surgery. Following
      mitral valve replacement he was weaned off cardiopulmonary bypass with an intra
      aortic balloon pump and high doses of inotropic support but continued to be
      hypotensive. Inspection of the heart showed right-sided dysfunction and evidence
      of pulmonary hypertension. Following the introduction of iNO he rapidly improved.
      He was successfully separated from the cardiopulmonary bypass support and
      subsequently made a full recovery and was discharged. We believe that this case
      demonstrates the utility of iNO in the management of pulmonary hypertension
      secondary to valvular disease in the acute setting. This is in contrast to the
      evidence against its utility in established pulmonary hypertension in chronic
      valvular heart disease. Further confirmation of this observation may lead to the
      therapeutic use of NO in this subpopulation of cardiac surgery patients.

PMID- 16572099
TI  - Stent-supported angioplasty of a residual coronary artery dissection following
      replacement of the ascending aorta for acute type A aortic dissection. A report
      of a successful case.
AB  - A 54-year-old-man suddenly experienced severe back pain while eating. On
      admission to our hospital, contrast-enhanced computed tomography revealed an
      acute type A aortic dissection, and emergency surgical repair was performed the
      same day. Through median sternotomy, graft replacement of the ascending aorta,
      including removal of the site of the intimal tear, was carried out under deep
      hypothermia and retrograde cerebral perfusion. Although the postoperative course
      was satisfactory, the patient suddenly complained of sever chest pain on
      postoperative day 23; the ECG trace showed anomalous alterations. Emergency
      coronary angiography revealed the presence of a wide coronary artery dissection
      from the entry of the left anterior descending aorta (LAD) to the re-entry of the
      left circumflex artery (LCX). Multiple stents were implanted in the LAD and LCX.
      After stenting, the chest symptoms remitted and the ECG trace was normal. The
      patient was discharged from our hospital on postoperative day 42.

PMID- 16572098
TI  - Role of computed tomography and magnetic resonance imaging in aortobronchial
      fistula diagnosis following aortic coarctation reparative surgery. Report of two
      cases.
AB  - Aortobronchial fistula (ABF) is an uncommon complication of aortic coarctation
      repair which may occur years after successful coarctation correction. It is
      invariably fatal if not diagnosed and treated. ABF diagnosis poses a challenge
      for clinicians and radiologists because of the difficulty in detecting the
      fistula and the risks associated with some of the diagnostic procedures. Two
      cases of ABF occurring 1 and 20 years after reparative surgery of aortic
      coarctation are reported. The advantages and disadvantages of different imaging
      procedures for the evaluation of patients with suspected ABF are reviewed and the
      role of computed tomography angiography and magnetic resonance imaging is
      underlined.

PMID- 16572100
TI  - Community-associated methicillin-resistant Staphylococcus aureus infection among
      healthy newborns--Chicago and Los Angeles County, 2004.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infection has long been
      associated with exposure in health-care settings but emerged in the late 1990s
      among previously healthy adults and children in the community. Community
      associated MRSA (CA-MRSA) infections most commonly are skin and soft-tissue
      infections; however, certain cases can progress to invasive tissue infections,
      bacteremia, and death. This report describes two independent investigations by
      local health departments, assisted by CDC, into outbreaks of MRSA skin infection
      among otherwise healthy, full-term newborns delivered at hospitals in Chicago,
      Illinois, and Los Angeles County, California. In both locations, MRSA
      transmission likely occurred in the newborn nursery; however, laboratory testing
      identified the MRSA strain as one that was described initially in association
      with CA-MRSA infections and outbreaks and that differs from predominant health
      care-associated MRSA (HA-MRSA) strains. The findings from these investigations
      underscore 1) the need for health-care providers to be aware that MRSA can cause
      skin infections among otherwise healthy newborns and 2) the importance of
      adhering to standard infection-control practices, including consistent hand
      hygiene, in newborn nurseries.

PMID- 16572101
TI  - Tuberculosis control activities after Hurricane Katrina--New Orleans, Louisiana,
      2005.
AB  - On August 29, 2005, when Hurricane Katrina struck the U.S. Gulf Coast, 130
      Louisiana residents in the greater New Orleans area were known to be undergoing
      treatment for tuberculosis (TB) disease. Standard treatment and cure of TB
      requires a multidrug regimen administered under directly observed therapy (DOT)
      for at least 6 months. This report updates previous information and summarizes TB
      cases reported as of December 31, 2005, among persons undergoing TB treatment in
      the New Orleans area when Hurricane Katrina made landfall and among persons who
      were evacuated and subsequently received a diagnosis of TB in other parts of the
      country. By October 13, 2005, through intensive local, state, and national
      efforts involving both government and private sector partners, all 130 TB
      patients from the New Orleans area had been located and, if still indicated, had
      resumed TB treatment. As a result of heightened public health surveillance among
      Hurricane Katrina evacuees, six other New Orleans evacuees began treatment (i.e.,
      two persons with known TB and four with previously undiagnosed TB) after arriving
      in other states. The success of these post-disaster TB control measures affirms
      the utility of alternative data sources during health-related emergencies and the
      importance of maintaining a strong TB control component in the public health
      sector.

PMID- 16572102
TI  - Racial and socioeconomic disparities in breastfeeding--United States, 2004.
AB  - The American Academy of Pediatrics recommends breastfeeding for at least the
      first year of life, and beyond for as long as mutually desired by mother and
      child. Not breastfeeding is associated with increased health risks for children,
      including otitis media, respiratory tract infections, diarrhea, and necrotizing
      enterocolitis. In addition, breastfeeding duration is inversely associated with
      risk for childhood overweight. Breastfeeding also is associated with health
      benefits for mothers, including reduced risk for ovarian cancer and premenopausal
      breast cancer. Breastfeeding rates differ substantially by race, socioeconomic
      level, and other demographic factors. For example, among children born during
      1982-1993, non-Hispanic black children were less likely than non-Hispanic white
      children to be breastfed at birth and at age 6 months, even when comparisons were
      among children in the same socioeconomic or other demographic subgroup. To obtain
      current estimates of racial and economic disparities in breastfeeding among U.S.
      children, CDC analyzed data from the 2004 National Immunization Survey (NIS).
      This report describes the results of that analysis, which indicated that 71.5% of
      non-Hispanic white children were ever breastfed compared with 50.1% of non
      Hispanic black children. Among those ever breastfed, 53.9% of non-Hispanic white
      and 43.2% of non-Hispanic black children continued breastfeeding until at least
      age 6 months. Disparities between black and white children existed within most
      socioeconomic subgroups studied. Public health programs should continue to
      promote breastfeeding initiation and increase support of breastfeeding
      continuation, especially among subgroups with the lowest rates (i.e., black,
      poor, and young mothers; mothers with less than a high school education; and
      mothers residing in rural areas).

PMID- 16572103
TI  - Death of a child after ingestion of a metallic charm--Minnesota, 2006.
AB  - Lead-based paint remains the most common source of lead exposure for children
      aged <6 years. However, one report determined that 34% of children aged <6 years
      with lead poisoning in Los Angeles County had been exposed to items containing
      lead that had been brought into the home. These items might include candy, folk
      and traditional medications, ceramic dinnerware, and metallic toys and trinkets.
      Exposures to some of these items can result in life-threatening BLLs of > or =100
      microg/dL (elevated BLLs are > or =10 microg/dL for children and > or =25
      microg/dL for adults). In 2004, a child in Oregon had a BLL of 123 microg/dL
      after ingesting a necklace with high lead content. The same year, the Consumer
      Product Safety Commission (CPSC) recalled 150 million pieces of imported metallic
      toy jewelry sold in vending machines. Some lead-contaminated items intended for
      use by children are manufactured in countries with limited government regulation
      of lead in consumer products. With the decline in BLLs in U.S. children,
      widespread education of the dangers of lead paint, and systematic reduction of
      lead hazards in U.S. housing, acute ingestion of lead-containing items has become
      increasingly more common as a source of life-threatening BLLs.

PMID- 16572104
TI  - Update: influenza activity--United States, March 12-18, 2006.
AB  - During March 12-18, 2006, the number of states reporting widespread influenza
      activity decreased to 23. Fourteen states reported regional activity, eight
      reported local activity, and five reported sporadic activity.

PMID- 16572105
TI  - Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain
      spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide
      for physicians and other health-care and public health professionals.
AB  - Tickborne rickettsial diseases (TBRD) continue to cause severe illness and death
      in otherwise healthy adults and children, despite the availability of low cost,
      effective antimicrobial therapy. The greatest challenge to clinicians is the
      difficult diagnostic dilemma posed by these infections early in their clinical
      course, when antibiotic therapy is most effective. Early signs and symptoms of
      these illnesses are notoriously nonspecific or mimic benign viral illnesses,
      making diagnosis difficult. In October 2004, CDC's Viral and Rickettsial Zoonoses
      Branch, in consultation with 11 clinical and academic specialists of Rocky
      Mountain spotted fever, human granulocytotropic anaplasmosis, and human
      monocytotropic ehrlichiosis, developed guidelines to address the need for a
      consolidated source for the diagnosis and management of TBRD. The preparers
      focused on the practical aspects of epidemiology, clinical assessment, treatment,
      and laboratory diagnosis of TBRD. This report will assist clinicians and other
      health-care and public health professionals to 1) recognize epidemiologic
      features and clinical manifestations of TBRD, 2) develop a differential diagnosis
      that includes and ranks TBRD, 3) understand that the recommendations for
      doxycycline are the treatment of choice for both adults and children, 4)
      understand that early empiric antibiotic therapy can prevent severe morbidity and
      death, and 5) report suspect or confirmed cases of TBRD to local public health
      authorities to assist them with control measures and public health education
      efforts.

PMID- 16572106
TI  - Propylthiouracil-induced anti-neutrophil cytoplasmic antibody-associated
      vasculitis.

PMID- 16572107
TI  - Cross-sectional relations of serum aldosterone and urine sodium excretion to
      urinary albumin excretion in a community-based sample.
AB  - Experimental models suggest that increased aldosterone and sodium intake are
      associated with renovascular damage and resultant proteinuria. We hypothesized
      that serum aldosterone and urinary sodium would be associated with urinary
      albumin excretion, an indicator of kidney damage. We evaluated 2700 participants
      (53% women, mean age 58 years) from the Framingham Offspring Study who attended a
      routine examination between 1995 and 1998, who were free of heart failure and
      renal failure, and underwent testing for serum aldosterone, spot urinary sodium,
      and urinary albumin excretion (urine albumin/creatinine ratio, UACR), the latter
      two indexed to urinary creatinine. Stepwise multivariable linear regression was
      used to evaluate the relations between UACR with urinary sodium index and serum
      aldosterone. In multivariable regression, log urinary sodium index was associated
      positively with log-UACR (P<0.0001). UACR levels in the fourth and fifth
      quintiles of urinary sodium index were 24% (95% confidence interval (CI) 3-49%),
      and twofold higher (95% CI 72-150%), respectively, relative to the lowest
      quintile (P-value for trend across quintiles <0.001). In multivariable models,
      log-transformed aldosterone was not related to log-UACR. The top quintile of
      serum aldosterone levels was associated with a 21% higher (95% 1-44%) UACR levels
      relative to the lowest quintile. Urinary albumin excretion was strongly and
      positively associated in a continuous fashion with urinary sodium excretion,
      whereas a weaker nonlinear positive relation with serum aldosterone was noted.
      Our cross-sectional observations raise the possibility that dietary salt intake
      may be associated with early renovascular damage.

PMID- 16572108
TI  - S1P(1)-selective agonist, SEW2871, ameliorates ischemic acute renal failure.
AB  - The pathogenesis of renal ischemia/reperfusion (I/R) injury involves activating
      several signal transduction cascade systems in endothelial cells. Sphingosine 1
      phospate (S1P) maintains endothelial cell integrity and inhibits lymphocyte
      egress via the specific S1P(1) receptor, and may play a role in reducing ischemic
      renal injury. We examined the protective effects of a newly identified S1P(1)
      selective agonist, SEW2871, on mouse renal I/R injury. Kidneys were harvested 1-4
      days after I/R injury for histopathology, immunofluorescence studies, and
      quantitative real-time reverse transcriptase-polymerase chain reaction analyses
      to assess the change in gene expression profiles of inflammation-associated
      cytokines and adhesion molecules. SEW2871 improved renal function with a 40%
      reduction in plasma creatinine levels (P<0.01) and a significant reduction in
      tubular necrosis scores (I/R only: 4.3+/-0.2 vs I/R+SEW2871: 2.5+/-0.4, P<0.05)
      24 h after ischemia. These changes were accompanied by 69% reduction in
      circulating lymphocytes, and 77 and 66% reduction in infiltrating neutrophils and
      macrophages in renal outer medulla, respectively (all P<0.01). The mRNA abundance
      of tumor necrotic factor-alpha (TNF-alpha), P-selectin, E-selectin, and
      intercellular adhesion molecule-1 (ICAM-1) was markedly increased by I/R injury
      (3.5-, 4.1-, 3.5-, and 4.8-folds, respectively, all P<0.05 vs sham). SEW2871
      treatment partially reversed the upregulation of TNF-alpha, P-selectin, and ICAM
      1 (47, 59, 54%, respectively, vs I/R control: 100%, all P<0.05). The reduction in
      protein expression of TNF-alpha, P-selectin, and ICAM-1 was further confirmed
      with immunofluorescence studies. These results suggest that SEW2871 ameliorates
      renal I/R injury by inhibiting lymphocyte egress and reducing pro-inflammatory
      molecules. This new class of renoprotective agent shows promise as a novel
      approach in preventing/treating ischemic acute renal failure.

PMID- 16572109
TI  - Evaluation of intra-renal oxygenation during water diuresis: a time-resolved
      study using BOLD MRI.
AB  - Hypoxia of the renal medulla is a possible precursor to the onset of acute renal
      failure in humans and therefore an understanding of the factors influencing the
      oxygenation status within the renal medulla is very important. Blood oxygenation
      level-dependent (BOLD) magnetic resonance imaging (MRI) has been shown to non
      invasively evaluate intra-renal oxygenation levels of the renal medulla in
      humans. A newly implemented three-dimensional (3-D) multiple gradient-recalled
      echo sequence, which permits examination of temporal responses to physiological
      or pharmacological stimuli, was used to monitor changes in intra-renal
      oxygenation status during water diuresis. Five healthy, young subjects (22+/-1.2
      years) took part in the study. BOLD MRI data were acquired before and after water
      loading. Studies were repeated on a separate day after the subjects were
      pretreated with naproxen. Water diuresis significantly improved renal medullary
      oxygenation levels in all subjects (pre-waterload=30.3 1/s vs post-waterload 22.8
      1/s); however, the temporal response was found to be subject dependent. In the
      presence of cyclooxygenase (COX) inhibition by naproxen, the improvement in
      oxygenation during water diuresis was completely abolished (pre-waterload=27.5
      1/s vs post-waterload 28.5 1/s). Monitoring of temporal responses for the first
      time during water loading allowed for an appreciation of subject dependence.
      Comparison of the temporal response in terms of slopes demonstrated a significant
      difference between the waterload studies with and without naproxen (with
      naproxen=0.056 1/(s min) vs without naproxen=0.25 1/(s min)). The observed
      effects of naproxen were consistent with previous findings with COX inhibition.

PMID- 16572110
TI  - Early post-transplant urinary IP-10 expression after kidney transplantation is
      predictive of short- and long-term graft function.
AB  - The early identification of renal transplant recipients at enhanced risk of
      developing acute and subclinical rejection would allow individualized adjustment
      of immunosuppression before functional graft injury occurs and would exclude
      these patients from drug-weaning studies. Protein and reverse transcriptase
      polymerase chain reaction-based analyses of candidate markers in urine open the
      opportunity to closely monitor kidney-transplanted patients non-invasively. The
      chemokine interferon-inducible protein 10 (IP-10; CXCL10) might be an interesting
      candidate to uncover ongoing immune processes within the graft. Urine samples
      from kidney-transplanted recipients were retrospectively analyzed for IP-10 mRNA
      and protein expression. IP-10 levels were correlated with the incidence of acute
      rejection episodes proven by histology and long-term graft function assessed by
      the glomerular filtration rate 6 months post transplantation. IP-10 expression in
      urine identified patients with ongoing acute rejection episodes several days
      before a biopsy was indicated by rising serum creatinine levels. Most
      importantly, elevated levels of urinary IP-10 protein within the first four
      postoperative weeks were predictive of graft function at 6 months even in the
      absence of acute rejection. These data reveal a correlation between elevated IP
      10 expression in urine at early time points post-transplantation and intragraft
      immune activation that leads to acute rejection and compromised long-term graft
      function.

PMID- 16572111
TI  - Renal hemodynamic responses to intrarenal infusion of acetylcholine: comparison
      with effects of PGE2 and NO donor.
AB  - Acetylcholine (Ach) could serve as a selective renal medullary vasodilator in
      studies of the mechanism of arterial pressure regulation; however, effects of
      intramedullary Ach infusion were disparate. In anesthetized rats, the total renal
      blood flow (RBF) was measured by renal artery probe, and local perfusion of the
      cortex (CBF), outer medulla (OMBF) and inner medulla (IMBF) as laser-Doppler (l
      D) flux. Renal artery infusion of Ach (60-150 microg/kg/h) significantly
      increased RBF by 17% and l-D parameters by 7-14%, without affecting arterial
      blood pressure (BP); the responses were prevented by inhibition of nitric oxide
      (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME).
      Intramedullary Ach (180 microg/kg/h) significantly increased OMBF by 9% and IMBF
      by 7% but also RBF and CBF (both 9%). Carbamylcholine (Cch, 15 or 30-60
      microg/kg/h), a stable Ach analog, increased CBF, OMBF, and IMBF by 5-8%; there
      was no dose dependency and, as with Ach, no preferential effect on medullary
      perfusion. Intramedullary infusion of prostaglandin E(2) (PGE2) (15 microg/kg/h),
      and S-nitroso-N-acetyl-D,L penicillamine (SNAP), an NO donor (15-30 mg/kg/h),
      significantly and substantially increased OMBF and IMBF only. Ach increased
      perfusion of all kidney zones by an NO-dependent mechanism. Infusion of Ach or
      Cch into the renal medullary interstitium failed to affect preferentially the
      medullary perfusion, in contrast to the well-demonstrable selective effects of
      PGE2 and SNAP. The reason was probably the Ach's dual opposed action,
      vasoconstrictor and vasorelaxant, on the intrarenal vasculature.

PMID- 16572112
TI  - Ras modulation of superoxide activates ERK-dependent fibronectin expression in
      diabetes-induced renal injuries.
AB  - Although previous studies have demonstrated that diabetic nephropathy is
      attributable to early extracellular matrix accumulation in glomerular mesangial
      cells, the molecular mechanism by which high glucose induces matrix protein
      deposition remains not fully elucidated. Rat mesangial cells pretreated with or
      without inhibitors were cultured in high-glucose or advanced glycation end
      product (AGE) conditions. Streptozotocin-induced diabetic rats were given
      superoxide dismutase (SOD)-conjugated propylene glycol to scavenge superoxide.
      Transforming growth factor (TGF)-beta1, fibronectin expression, Ras, ERK, p38,
      and c-Jun activation of glomerular mesangial cells or urinary albumin secretion
      were assessed. Superoxide, not nitric oxide or hydrogen peroxide, mediated high
      glucose- and AGE-induced TGF-beta1 and fibronectin expression. Pretreatment with
      diphenyliodonium, not allopurinol or rotenone, reduced high-glucose and AGE
      augmentation of superoxide synthesis and fibronection expression. High glucose
      and AGEs rapidly enhanced Ras activation and progressively increased cytosolic
      ERK and nuclear c-Jun activation. Inhibiting Ras by manumycin A reduced the
      stimulatory effects of high glucose and AGEs on superoxide and fibronectin
      expression. SOD or PD98059 pretreatment reduced high-glucose and AGE promotion of
      ERK and c-Jun activation. Exogenous SOD treatment in diabetic rats significantly
      attenuated diabetes induction of superoxide, urinary albumin excretion, 8-hydroxy
      2'-deoxyguanosine, TGF-beta1, and fibronectin immunoreactivities in renal
      glomerular mesangial cells. Ras induction of superoxide activated ERK-dependent
      fibrosis-stimulatory factor and extracellular matrix gene transcription of
      mesangial cells. Reduction of oxidative stress by scavenging superoxide may
      provide an alternative strategy for controlling diabetes-induced early renal
      injury.

PMID- 16572113
TI  - Effect of fluvastatin on apolipoprotein-defined lipoprotein subclasses in
      patients with chronic renal insufficiency.
AB  - According to the concept of apolipoprotein (apo)-defined lipoproteins, apoA-I
      containing lipoproteins consist of two subclasses referred to as lipoprotein A-I
      (LpA-I) and lipoprotein A-I:A-II (LpA-I:A-II), and apoB-containing lipoproteins
      of five subclasses, namely lipoprotein B (LpB), lipoprotein B:C (LpB:C),
      lipoprotein B:E (LpB:E), lipoprotein B:C:E (LpB:C:E), and lipoprotein A
      II:B:C:D:E (LpA-II:B:C:D:E). The purpose of this study was to determine the
      levels of apoA-I- and apoB-containing lipoprotein subclasses before and after
      fluvastatin treatment of patients with chronic renal insufficiency. ApoA-I- and
      apoB-containing lipoprotein subclasses were measured in 15 patients with chronic
      renal failure and 15 asymptomatic subjects. The effect of fluvastatin on
      lipoprotein subclasses was determined in a randomized, double-blind, placebo
      controlled, two-way, treatment period crossover study. Patients were administered
      fluvastatin 40 mg/day or placebo during 8 weeks in a randomized order. Patients
      were characterized by significantly higher levels of LpB (P < 0.001), LpB:C (P <
      0.001), and LpB:E (P < 0.05), and slightly higher levels of LpB:C:E and LpA
      II:B:C:D:E than controls. The levels of LpA-I:A-II were significantly lower (P <
      0.01) in patients than controls. Fluvastatin treatment reduced all apoB
      containing subclasses, but only the reduced level of LpB subclass was
      statistically significant (P < 0.02). The levels of LpA-I and LpA-I:A-II were not
      affected. Fluvastatin treatment reduced and normalized LpB and LpB:E subclasses.
      Although slightly reduced, the levels of markedly atherogenic LpB:C subclass were
      not normalized. The potential role of LpB:C on the progression of coronary artery
      disease in chronic renal insufficiency remains to be determined in future
      studies.

PMID- 16572114
TI  - Renal risk and renoprotection among ethnic groups with type 2 diabetic
      nephropathy: a post hoc analysis of RENAAL.
AB  - Type 2 diabetes is becoming the leading cause of end-stage renal disease (ESRD)
      worldwide. Prevalence of ESRD and the antihypertensive response to renin
      angiotensin system intervention are suggested to vary among different
      ethnicities. The Reduction in Endpoints in Non-insulin dependent diabetes
      mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study, which
      included different ethnic groups, demonstrated a renoprotective effect of
      losartan. A post hoc analysis from RENAAL was performed where we examined in each
      ethnic group the ESRD risk, identified independent predictors for ESRD, effect of
      degree of baseline albuminuria, effect of 6-month antiproteinuric response to
      therapy on ESRD, and renoprotective effect of losartan assessed by albuminuria
      reduction and ESRD. Baseline albuminuria was the strongest predictor for ESRD in
      every ethnic group. Albuminuria reduction was associated with reduced risk of
      ESRD while losartan reduced albuminuria in every ethnic group. When accounting
      for independent predictors of ESRD, losartan exhibited renoprotection in all
      ethnic groups. In this type 2 diabetic population with nephropathy, baseline
      albuminuria is the predominant risk parameter for ESRD; early antiproteinuric
      effect of losartan predicts long-term renoprotection; and losartan appears to be
      renoprotective in all ethnic groups. Since the RENAAL study was not powered to
      determine ethnic responses, these results underline the need for prospective
      trials where the aim is renal protection among different ethnic groups.

PMID- 16572115
TI  - Transforming growth factor beta regulates cyclooxygenase-2 in glomerular
      mesangial cells.
AB  - This study examines the hypothesis that transforming growth factor beta (TGFbeta)
      regulates cyclooxygenase-2 (COX-2) and induces prostaglandin E synthase (mPGES-1)
      in rat mesangial cells. COX-2 expression was determined by Northern blot analysis
      after treatment with either TGFbeta1 or the selective COX-2 inhibitor, NS398.
      mPGES-1 expression was determined by real-time polymerase chain reaction. The
      effect of TGFbeta1 on COX-2 gene transcription was assessed using a luciferase
      reporter assay, and mRNA stability was also determined. To determine whether
      TGFbeta1 activates elements of the COX-2 promoter, we performed gel shift
      analyses to examine activation of activator protein-1 (AP-1) and nuclear factor
      kappaB (NF-kappaB). Prostaglandin E(2) (PGE(2)) and thromboxane B2 (TxB2)
      production was assayed by enzyme immunoassay. Finally, the pathophysiological
      relevance of COX-2 inhibition on the downstream effects of TGFbeta was assessed
      by examining collagen type I mRNA and net collagen production. COX-2 mRNA and
      mPGES-1 were induced after treatment with TGFbeta1 for 4 h, and this rise was
      accompanied by a three-fold increase in PGE(2) production that could be
      antagonized by selective inhibition of COX-2 with NS398. TGFbeta1 increased
      transcription by approximately 50% and activated both AP-1 and NF-kappaB. These
      effects were antagonized by co-treatment with NS398. Treatment with TGFbeta1 also
      doubled the half-life of COX-2 mRNA. Neither collagen type I mRNA nor net
      collagen production were altered by co-treatment with NS398. In conclusion, these
      results indicate that TGFbeta stimulates COX-2 and mPGES-1, with additional
      effects on transcription and stability of COX-2 mRNA.

PMID- 16572116
TI  - VEGF receptor 2 blockade leads to renal cyst formation in mice.
AB  - Polycystic kidney disease (PKD) is associated with mutations in PKD1 and PKD2 and
      vascular abnormalities. The links between the epithelial and vascular defects,
      however, are poorly understood. Vascular endothelial growth factor (VEGF) has
      been shown to be critical for normal kidney development. In animal models,
      blockade of VEGF in the perinatal period can lead to abnormal glomerular
      development, impaired nephrogenesis, proteinuria, and renal failure. We
      hypothesized that brief blockade of VEGF signaling during early postnatal kidney
      development can lead to renal cyst development. On days 2 and 4 of life, CD-1
      mice were treated with antibodies generated against the extracellular portion of
      the VEGF receptor 2 (DC101), the area of the receptor where VEGF binding occurs.
      Mice developed renal cysts between 2 and 3 weeks. The DC101-treated mice also had
      increased cell proliferation in the renal tubule epithelium. In addition, mice
      receiving DC101 developed abnormal glomeruli, proteinuria, and patchy cellular
      infiltrates. Early disruption of VEGFR-2 signaling during the perinatal period
      results in renal cyst formation, impaired glomerulogenesis, and inflammation.
      VEGF could be a key link between vascular and cystic changes in kidney cyst
      formation.

PMID- 16572117
TI  - 'Low-dose' dopamine worsens renal perfusion in patients with acute renal failure.
AB  - 'Low-dose' dopamine is frequently used in intensive care units (ICU) for its
      presumed renoprotective effects, but prospective and retrospective studies have
      so far not proven prevention or amelioration of renal injury. Data on renal
      perfusion following dopamine infusion are limited. In order to circumvent the
      problem of patient heterogeneity in the ICU setting, we used a crossover design
      in a prospective, double-blind randomized controlled study to investigate the
      effect of 'low-dose' dopamine on renal resistance indices, as determined by
      Doppler ultrasound. Forty patients, 10 without and 30 with acute renal failure
      (ARF, defined as doubling of baseline creatinine or an increase above 2 mg/dl),
      were included. Dopamine (2 mug/kg min) or placebo was given intravenously in
      alternating sequence for four subsequent periods of 60 min, starting randomly
      with either dopamine or placebo. Resistive (RI) and pulsatility index (PI) were
      closely correlated, positively related to serum creatinine values at baseline and
      highly reproducible during the two paired infusion periods. Dopamine reduced
      renal vascular resistance in patients without ARF (median RI/PI from 0.70 to
      0.65/1.20 to 1.07, P<0.01) but increased resistance indices in patients with ARF
      (median RI/PI from 0.77 to 0.81/1.64 to 1.79, P<0.01) in the absence of effects
      on systemic hemodynamics. Subgroup analysis of patients with ARF revealed that
      dopamine induced renal vasoconstriction above 55 years (n=22) and in patients not
      receiving norepinephrine (n=20). In conclusion 'low-dose' dopamine can worsen
      renal perfusion in patients with ARF, which adds to the rationale for abandoning
      the routine use of 'low-dose' dopamine in critically ill patients.

PMID- 16572118
TI  - Angiotensin II production and distribution in the kidney: I. A kinetic model.
AB  - Information on the levels of angiotensin II (Ang II) and its receptors in the
      various renal tissue compartments is still incomplete. A model is presented
      describing the kinetics of Ang II production, distribution, and disposal in the
      renal cortex. Basic features are: (1) the model is designed to derive, from Ang
      II measurements in blood and in whole tissue, estimates of the local densities of
      the Ang II type 1 (AT(1)) and type 2 (AT(2)) receptors, and to calculate the
      concentrations of endocrine and paracrine Ang II they actually 'see'; (2)
      glomerular and peritubular tissue are conceived as separate regions (glomerular
      region (Glom), peritubular region (Pt)); (3) in Glom and in Pt, Ang II is
      homogeneously distributed in capillary blood and in interstitial fluid; (4) the
      model allows for local Ang II concentration gradients between interstitium and
      blood; (5) Ang II from the circulation diffuses into the interstitium of Glom
      after convective transcapillary transport; (6) Ang II produced in tubules or Pt
      enters the microcirculation through diffusive overflow from interstitium; (7) the
      presence of cell-surface-bound Ang II depends on the reaction with AT(1) and
      AT(2) receptors, and the presence of intracellular Ang II depends on the
      internalization of Ang II - AT(1) receptor complex; and (8) the model provides
      for glomerular filtration, vasopeptidase-mediated degradation, and intracellular
      degradation as mechanisms of elimination. This model can serve as a framework for
      detailed quantitative studies of the renin-angiotensin system in the kidney.

PMID- 16572119
TI  - Renal pathology in idiopathic membranous nephropathy: a new perspective.
AB  - Histology findings in idiopathic membranous nephropathy (MGN) have been
      associated with the risk of renal failure, but whether they are independent of
      the clinical variables at the time of biopsy, predict rate of progression, or
      should guide therapy is uncertain. Renal biopsies of 389 adult MGN patients were
      evaluated semiquantitatively for interstitial fibrosis, tubular atrophy, vascular
      sclerosis, focal and segmental glomerulosclerosis lesions (FSGS), complement
      deposition, and stage and synchrony of deposits by electron microscopy (EM).
      Associations were tested between these findings and the rate of renal function
      decline (slope), renal survival, remission in proteinuria, and response to
      immunosuppression. Patients with a greater degree of tubulo-interstitial disease,
      vascular sclerosis, and secondary FSGS were older, had a higher mean arterial
      pressure, and a lower creatinine clearance at presentation. Although these
      histologic features were associated with a reduced renal survival, they did not
      predict this outcome independently of the baseline clinical variables nor did
      they correlate with the rate of decline in function or with baseline proteinuria.
      Furthermore, the severity of tubulo-interstitial and vascular lesions did not
      preclude a remission in proteinuria in those who received immunosuppressive
      therapy. Neither stage nor synchronicity of EM deposits nor the amount of
      complement deposition predicted renal survival but the latter did correlate with
      progression rate. In MGN, certain histologic changes are associated with renal
      survival outcome. However, the indicators of chronic injury are associated with
      age, blood pressure, and creatinine clearance at presentation and not with rate
      of disease progression or initial proteinuria.

PMID- 16572120
TI  - Testing the homocysteine hypothesis in end-stage renal disease: Problems and a
      possible solution.
AB  - The homocysteine hypothesis states that circulating homocysteine is a vascular
      toxin in concentrations that occur in the general population and in renal
      failure. This hypothesis is currently being tested in the Kidney and End State
      Renal Disease Study (HOST), but data have emerged since the HOST began that
      suggest its results will be inconclusive. The crucial treatment component in the
      HOST is folic acid, but its effect is likely to be lost because the American food
      supply is now fortified with folic acid. A second concern is that the very high
      doses of folic acid and pyridoxine being used in the HOST may confound the
      results. Finally, confounding due to 'reverse epidemiology' was not considered
      when the HOST was designed. Parenteral vitamin B(12) is a highly promising
      therapy for homocysteine reduction in end-stage renal disease that merits careful
      investigation. Clinical trials using it to test the homocysteine hypothesis will
      avoid the problems inherent in the HOST.

PMID- 16572121
TI  - A loss-of-function RNA interference screen for molecular targets in cancer.
AB  - The pursuit of novel therapeutic agents in cancer relies on the identification
      and validation of molecular targets. Hallmarks of cancer include self-sufficiency
      in growth signals and evasion from apoptosis; genes that regulate these processes
      may be optimal for therapeutic attack. Here we describe a loss-of-function screen
      for genes required for the proliferation and survival of cancer cells using an
      RNA interference library. We used a doxycycline-inducible retroviral vector for
      the expression of small hairpin RNAs (shRNAs) to construct a library targeting
      2,500 human genes. We used retroviral pools from this library to infect cell
      lines representing two distinct molecular subgroups of diffuse large B-cell
      lymphoma (DLBCL), termed activated B-cell-like DLBCL and germinal centre B-cell
      like DLBCL. Each vector was engineered to contain a unique 60-base-pair 'bar
      code', allowing the abundance of an individual shRNA vector within a population
      of transduced cells to be measured using microarrays of the bar-code sequences.
      We observed that a subset of shRNA vectors was depleted from the transduced cells
      after three weeks in culture only if shRNA expression was induced. In activated B
      cell-like DLBCL cells, but not germinal centre B-cell-like DLBCL cells, shRNAs
      targeting the NF-kappaB pathway were depleted, in keeping with the essential role
      of this pathway in the survival of activated B-cell-like DLBCL. This screen
      uncovered CARD11 as a key upstream signalling component responsible for the
      constitutive IkappaB kinase activity in activated B-cell-like DLBCL. The
      methodology that we describe can be used to establish a functional taxonomy of
      cancer and help reveal new classes of therapeutic targets distinct from known
      oncogenes.

PMID- 16572122
TI  - Copper-containing plastocyanin used for electron transport by an oceanic diatom.
AB  - The supply of some essential metals to pelagic ecosystems is less than the
      demand, so many phytoplankton have slow rates of photosynthetic production and
      restricted growth. The types and amounts of metals required by phytoplankton
      depends on their evolutionary history and on their adaptations to metal
      availability, which varies widely among ocean habitats. Diatoms, for example,
      need considerably less iron (Fe) to grow than chlorophyll-b-containing taxa, and
      the oceanic species demand roughly one-tenth the amount of coastal strains. Like
      Fe, copper (Cu) is scarce in the open sea, but notably higher concentrations of
      it are required for the growth of oceanic than of coastal isolates. Here we
      report that the greater Cu requirement in an oceanic diatom, Thalassiosira
      oceanica, is entirely due to a single Cu-containing protein, plastocyanin, which-
      until now--was only known to exist in organisms with chlorophyll b and
      cyanobacteria. Algae containing chlorophyll c, including the closely related
      coastal species T. weissflogii, are thought to lack plastocyanin and contain a
      functionally equivalent Fe-containing homologue, cytochrome c6 (ref. 9). Copper
      deficiency in T. oceanica inhibits electron transport regardless of Fe status,
      implying a constitutive role for plastocyanin in the light reactions of
      photosynthesis in this species. The results suggest that selection pressure
      imposed by Fe limitation has resulted in the use of a Cu protein for
      photosynthesis in an oceanic diatom. This biochemical switch reduces the need for
      Fe and increases the requirement for Cu, which is relatively more abundant in the
      open sea.

PMID- 16572128
TI  - Britannica attacks.

PMID- 16572127
TI  - Brown's budget briefing.

PMID- 16572123
TI  - High-potency marijuana impairs executive function and inhibitory motor control.
AB  - Human performance studies have usually relied on low-potency marijuana (4% THC)
      for determining THC-induced impairment. The present study was designed to assess
      the effects of high-potency marijuana (13% THC) on human performance. In all, 20
      recreational users of marijuana participated in a double-blind, placebo
      controlled, three way cross-over study. The treatments consisted of single doses
      of 0, 250, and 500 microg/kg THC. Performance tests were conducted at regular
      intervals between 15 min and 6 h postsmoking and included measures of motor
      control (Critical tracking task), executive function (Tower of London) motor
      impulsivity (Stop signal task), and risk taking (Iowa gambling task). THC
      significantly impaired performance in the Critical tracking task and decreased
      the number of correct decisions in the Tower of London task. In addition, THC
      significantly increased stop reaction time and the proportions of commission and
      omission errors in the Stop signal task. THC-induced impairments lasted up to 6 h
      postsmoking as indicated by the absence of a THC x Time after smoking
      interaction. Effect sizes for performance impairments produced by THC 250
      microg/kg were relatively low but generally increased by a factor of two in case
      of THC 500 microg/kg. These data suggest that high potency marijuana consistently
      impairs executive function and motor control. Use of higher doses of THC in
      controlled studies may offer a reliable indication of THC induced impairment as
      compared to lower doses of THC that have traditionally been used in performance
      studies.

PMID- 16572129
TI  - Astrobiology at ten.

PMID- 16572131
TI  - Space scientists get double reprieve.

PMID- 16572132
TI  - Stem cells from testes: could it work?

PMID- 16572134
TI  - Italians put science chief on the spot.

PMID- 16572133
TI  - US to rule on research patent.

PMID- 16572135
TI  - Scans suggest IQ scores reflect brain structure.

PMID- 16572137
TI  - Credit where credit's due.

PMID- 16572138
TI  - More whale strandings are linked to sonar.

PMID- 16572141
TI  - Climate science: the son also rises.

PMID- 16572143
TI  - Too little, too late?

PMID- 16572142
TI  - Mitochondrial disease: powerhouse of disease.

PMID- 16572144
TI  - Populations who test drugs should benefit from them.

PMID- 16572145
TI  - Ecological society supports its African counterparts.

PMID- 16572152
TI  - Quantum mechanics in the brain.

PMID- 16572146
TI  - Dogs can play useful role as sentinel hosts for disease.

PMID- 16572147
TI  - Shared data are key to beating threat from flu.

PMID- 16572153
TI  - Ecology: green and pleasant trials.

PMID- 16572154
TI  - Planetary science: Saturn's bared mini-moons.

PMID- 16572155
TI  - Neuroscience: rewinding the memory record.

PMID- 16572157
TI  - Quantum metrology: size isn't everything.

PMID- 16572158
TI  - Materials science: nanostructures in a new league.

PMID- 16572159
TI  - Cognitive science: brain development and IQ.

PMID- 16572160
TI  - X-ray imaging: soft focus.

PMID- 16572161
TI  - Environmental chemistry: boiling up an acid plume.

PMID- 16572163
TI  - Eukaryotic evolution, changes and challenges.
AB  - The idea that some eukaryotes primitively lacked mitochondria and were true
      intermediates in the prokaryote-to-eukaryote transition was an exciting prospect.
      It spawned major advances in understanding anaerobic and parasitic eukaryotes and
      those with previously overlooked mitochondria. But the evolutionary gap between
      prokaryotes and eukaryotes is now deeper, and the nature of the host that
      acquired the mitochondrion more obscure, than ever before.

PMID- 16572162
TI  - Biopolymers: shape memory in spider draglines.
AB  - The ductility and strength of spider draglines means that they outperform the
      best synthetic fibres, but surprisingly little is known about the torsional
      properties of this remarkable filament. Unlike a mountain climber swinging from a
      rope, a spider suspended from its silk thread hardly ever twists. Here we show
      that a spider dragline has a torsional shape 'memory' in that it can reversibly
      and totally recover its initial form without any external stimulus; its observed
      relaxation dynamics indicate that these biological molecules have successively
      different torsional constants.

PMID- 16572164
TI  - The evolution of galaxies from primeval irregulars to present-day ellipticals.
AB  - Galaxy formation is believed to proceed in a 'bottom up' manner, starting with
      the formation of small clumps of gas and stars that then merge hierarchically
      into giant systems. The baryonic gas loses thermal energy by radiative cooling
      and falls towards the centres of the new galaxies, while supernovae blow gas out.
      Any realistic model therefore requires a proper treatment of these processes, but
      hitherto this has been far from satisfactory. Here we report a simulation that
      follows evolution from the earliest stages of galaxy formation through the period
      of dynamical relaxation, at which point the resulting galaxy is in its final
      form. The bubble structures of gas revealed in our simulation (for times of less
      than 3 x 10(8) years) resemble closely high-redshift Lyman-alpha emitters. After
      10(9) years, these bodies are dominated by stellar continuum radiation and then
      resemble the Lyman break galaxies, which are high-redshift star-forming galaxies.
      At this point, the abundance of elements heavier than helium ('metallicity')
      appears to be solar. After 1.3 x 10(10) years, these galaxies resemble present
      day ellipticals.

PMID- 16572165
TI  - 100-metre-diameter moonlets in Saturn's A ring from observations of 'propeller'
      structures.
AB  - Saturn's main rings are composed predominantly of water-ice particles ranging
      between about 1 centimetre and 10 metres in radius. Above this size range, the
      number of particles drops sharply, according to the interpretation of spacecraft
      and stellar occultations. Other than the gap moons Pan and Daphnis (the
      provisional name of S/2005 S1), which have sizes of several kilometres, no
      individual bodies in the rings have been directly observed, and the population of
      ring particles larger than ten metres has been essentially unknown. Here we
      report the observation of four longitudinal double-streaks in an otherwise bland
      part of the mid-A ring. We infer that these 'propeller'-shaped perturbations
      arise from the effects of embedded moonlets approximately 40 to 120 m in
      diameter. Direct observation of this phenomenon validates models of proto
      planetary disks in which similar processes are posited. A population of moonlets,
      as implied by the size distribution that we find, could help explain gaps in the
      more tenuous regions of the Cassini division and the C ring. The existence of
      such large embedded moonlets is most naturally compatible with a ring originating
      in the break-up of a larger body, but accretion from a circumplanetary disk is
      also plausible if subsequent growth onto large particles occurs after the primary
      accretion phase has concluded.

PMID- 16572166
TI  - Controlled multiple reversals of a ratchet effect.
AB  - A single particle confined in an asymmetric potential demonstrates an anticipated
      ratchet effect by drifting along the 'easy' ratchet direction when subjected to
      non-equilibrium fluctuations. This well-known effect can, however, be
      dramatically changed if the potential captures several interacting particles.
      Here we demonstrate that the inter-particle interactions in a chain of repelling
      particles captured by a ratchet potential can, in a controllable way, lead to
      multiple drift reversals, with the drift sign alternating from positive to
      negative as the number of particles per ratchet period changes from odd to even.
      To demonstrate experimentally the validity of this very general prediction, we
      performed transport measurements on a.c.-driven vortices trapped in a
      superconductor by an array of nanometre-scale asymmetric traps. We found that the
      direction of the vortex drift does undergo multiple reversals as the vortex
      density is increased, in excellent agreement with the model predictions. This
      drastic change in the drift behaviour between single- and multi-particle systems
      can shed some light on the different behaviour of ratchets and biomembranes in
      two drift regimes: diluted (single particles) and concentrated (interacting
      particles).

PMID- 16572167
TI  - Ab initio determination of solid-state nanostructure.
AB  - Advances in materials science and molecular biology followed rapidly from the
      ability to characterize atomic structure using single crystals. Structure
      determination is more difficult if single crystals are not available. Many
      complex inorganic materials that are of interest in nanotechnology have no
      periodic long-range order and so their structures cannot be solved using
      crystallographic methods. Here we demonstrate that ab initio structure solution
      of these nanostructured materials is feasible using diffraction data in
      combination with distance geometry methods. Precise, sub-angstrom resolution
      distance data are experimentally available from the atomic pair distribution
      function (PDF). Current PDF analysis consists of structure refinement from
      reasonable initial structure guesses and it is not clear, a priori, that
      sufficient information exists in the PDF to obtain a unique structural solution.
      Here we present and validate two algorithms for structure reconstruction from
      precise unassigned interatomic distances for a range of clusters. We then apply
      the algorithms to find a unique, ab initio, structural solution for C60 from PDF
      data alone. This opens the door to sub-angstrom resolution structure solution of
      nanomaterials, even when crystallographic methods fail.

PMID- 16572168
TI  - Melting in the Earth's deep upper mantle caused by carbon dioxide.
AB  - The onset of partial melting beneath mid-ocean ridges governs the cycling of
      highly incompatible elements from the mantle to the crust, the flux of key
      volatiles (such as CO2, He and Ar) and the rheological properties of the upper
      mantle. Geophysical observations indicate that melting beneath ridges begins at
      depths approaching 300 km, but the cause of this melting has remained unclear.
      Here we determine the solidus of carbonated peridotite from 3 to 10 GPa and
      demonstrate that melting beneath ridges may occur at depths up to 330 km,
      producing 0.03-0.3% carbonatite liquid. We argue that these melts promote
      recrystallization and realignment of the mineral matrix, which may explain the
      geophysical observations. Extraction of incipient carbonatite melts from deep
      within the oceanic mantle produces an abundant source of metasomatic fluids and a
      vast mantle residue depleted in highly incompatible elements and fractionated in
      key parent-daughter elements. We infer that carbon, helium, argon and highly
      incompatible heat-producing elements (such as uranium, thorium and potassium) are
      efficiently scavenged from depths of approximately 200-330 km in the upper
      mantle.

PMID- 16572169
TI  - Altruism through beard chromodynamics.
AB  - The evolution of altruism, a behaviour that benefits others at one's own fitness
      expense, poses a darwinian paradox. The paradox is resolved if many interactions
      are with related individuals so that the benefits of altruism are reaped by
      copies of the altruistic gene in other individuals, a mechanism called kin
      selection. However, recognition of altruists could provide an alternative route
      towards the evolution of altruism. Arguably the simplest recognition system is a
      conspicuous, heritable tag, such as a green beard. Despite the fact that such
      genes have been reported, the 'green beard effect' has often been dismissed
      because it is unlikely that a single gene can code for altruism and a
      recognizable tag. Here we model the green beard effect and find that if
      recognition and altruism are always inherited together, the dynamics are highly
      unstable, leading to the loss of altruism. In contrast, if the effect is caused
      by loosely coupled separate genes, altruism is facilitated through beard
      chromodynamics in which many beard colours co-occur. This allows altruism to
      persist even in weakly structured populations and implies that the green beard
      effect, in the form of a fluid association of altruistic traits with a
      recognition tag, can be much more prevalent than hitherto assumed.

PMID- 16572170
TI  - Chance and necessity in the evolution of minimal metabolic networks.
AB  - It is possible to infer aspects of an organism's lifestyle from its gene content.
      Can the reverse also be done? Here we consider this issue by modelling evolution
      of the reduced genomes of endosymbiotic bacteria. The diversity of gene content
      in these bacteria may reflect both variation in selective forces and contingency
      dependent loss of alternative pathways. Using an in silico representation of the
      metabolic network of Escherichia coli, we examine the role of contingency by
      repeatedly simulating the successive loss of genes while controlling for the
      environment. The minimal networks that result are variable in both gene content
      and number. Partially different metabolisms can thus evolve owing to contingency
      alone. The simulation outcomes do preserve a core metabolism, however, which is
      over-represented in strict intracellular bacteria. Moreover, differences between
      minimal networks based on lifestyle are predictable: by simulating their
      respective environmental conditions, we can model evolution of the gene content
      in Buchnera aphidicola and Wigglesworthia glossinidia with over 80% accuracy. We
      conclude that, at least for the particular cases considered here, gene content of
      an organism can be predicted with knowledge of its distant ancestors and its
      current lifestyle.

PMID- 16572172
TI  - Intellectual ability and cortical development in children and adolescents.
AB  - Children who are adept at any one of the three academic 'R's (reading, writing
      and arithmetic) tend to be good at the others, and grow into adults who are
      similarly skilled at diverse intellectually demanding activities. Determining the
      neuroanatomical correlates of this relatively stable individual trait of general
      intelligence has proved difficult, particularly in the rapidly developing brains
      of children and adolescents. Here we demonstrate that the trajectory of change in
      the thickness of the cerebral cortex, rather than cortical thickness itself, is
      most closely related to level of intelligence. Using a longitudinal design, we
      find a marked developmental shift from a predominantly negative correlation
      between intelligence and cortical thickness in early childhood to a positive
      correlation in late childhood and beyond. Additionally, level of intelligence is
      associated with the trajectory of cortical development, primarily in frontal
      regions implicated in the maturation of intelligent activity. More intelligent
      children demonstrate a particularly plastic cortex, with an initial accelerated
      and prolonged phase of cortical increase, which yields to equally vigorous
      cortical thinning by early adolescence. This study indicates that the
      neuroanatomical expression of intelligence in children is dynamic.

PMID- 16572171
TI  - Analysis of the DNA sequence and duplication history of human chromosome 15.
AB  - Here we present a finished sequence of human chromosome 15, together with a high
      quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a
      high rate of segmental duplication, we have carried out a detailed analysis of
      the duplication structure of the chromosome. Segmental duplications in chromosome
      15 are largely clustered in two regions, on proximal and distal 15q; the proximal
      region is notable because recombination among the segmental duplications can
      result in deletions causing Prader-Willi and Angelman syndromes. Sequence
      analysis shows that the proximal and distal regions of 15q share extensive
      ancient similarity. Using a simple approach, we have been able to reconstruct
      many of the events by which the current duplication structure arose. We find that
      most of the intrachromosomal duplications seem to share a common ancestry.
      Finally, we demonstrate that some remaining gaps in the genome sequence are
      probably due to structural polymorphisms between haplotypes; this may explain a
      significant fraction of the gaps remaining in the human genome.

PMID- 16572173
TI  - A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel
      homologue.
AB  - The nematode Caenorhabditis elegans is commonly used as a genetic model organism
      for dissecting integration of the sensory and motor systems. Despite extensive
      genetic and behavioural analyses that have led to the identification of many
      genes and neural circuits involved in regulating C. elegans locomotion behaviour,
      it remains unclear whether and how somatosensory feedback modulates motor output
      during locomotion. In particular, no stretch receptors have been identified in C.
      elegans, raising the issue of whether stretch-receptor-mediated proprioception is
      used by C. elegans to regulate its locomotion behaviour. Here we have
      characterized TRP-4, the C. elegans homologue of the mechanosensitive TRPN
      channel. We show that trp-4 mutant worms bend their body abnormally, exhibiting a
      body posture distinct from that of wild-type worms during locomotion, suggesting
      that TRP-4 is involved in stretch-receptor-mediated proprioception. We show that
      TRP-4 acts in a single neuron, DVA, to mediate its function in proprioception,
      and that the activity of DVA can be stimulated by body stretch. DVA both
      positively and negatively modulates locomotion, providing a unique mechanism
      whereby a single neuron can fine-tune motor activity. Thus, DVA represents a
      stretch receptor neuron that regulates sensory-motor integration during C.
      elegans locomotion.

PMID- 16572174
TI  - A silicon transporter in rice.
AB  - Silicon is beneficial to plant growth and helps plants to overcome abiotic and
      biotic stresses by preventing lodging (falling over) and increasing resistance to
      pests and diseases, as well as other stresses. Silicon is essential for high and
      sustainable production of rice, but the molecular mechanism responsible for the
      uptake of silicon is unknown. Here we describe the Low silicon rice 1 (Lsi1)
      gene, which controls silicon accumulation in rice, a typical silicon-accumulating
      plant. This gene belongs to the aquaporin family and is constitutively expressed
      in the roots. Lsi1 is localized on the plasma membrane of the distal side of both
      exodermis and endodermis cells, where casparian strips are located. Suppression
      of Lsi1 expression resulted in reduced silicon uptake. Furthermore, expression of
      Lsi1 in Xenopus oocytes showed transport activity for silicon only. The
      identification of a silicon transporter provides both an insight into the silicon
      uptake system in plants, and a new strategy for producing crops with high
      resistance to multiple stresses by genetic modification of the root's silicon
      uptake capacity.

PMID- 16572175
TI  - Regulation of cancer cell migration and bone metastasis by RANKL.
AB  - Bone metastases are a frequent complication of many cancers that result in severe
      disease burden and pain. Since the late nineteenth century, it has been thought
      that the microenvironment of the local host tissue actively participates in the
      propensity of certain cancers to metastasize to specific organs, and that bone
      provides an especially fertile 'soil'. In the case of breast cancers, the local
      chemokine milieu is now emerging as an explanation for why these tumours
      preferentially metastasize to certain organs. However, as the inhibition of
      chemokine receptors in vivo only partially blocks metastatic behaviour, other
      factors must exist that regulate the preferential metastasis of breast cancer
      cells. Here we show that the cytokine RANKL (receptor activator of NF-kappaB
      ligand) triggers migration of human epithelial cancer cells and melanoma cells
      that express the receptor RANK. RANK is expressed on cancer cell lines and breast
      cancer cells in patients. In a mouse model of melanoma metastasis, in vivo
      neutralization of RANKL by osteoprotegerin results in complete protection from
      paralysis and a marked reduction in tumour burden in bones but not in other
      organs. Our data show that local differentiation factors such as RANKL have an
      important role in cell migration and the tissue-specific metastatic behaviour of
      cancer cells.

PMID- 16572176
TI  - Analysis of a RanGTP-regulated gradient in mitotic somatic cells.
AB  - The RanGTPase cycle provides directionality to nucleocytoplasmic transport,
      regulating interactions between cargoes and nuclear transport receptors of the
      importin-beta family. The Ran-importin-beta system also functions in mitotic
      spindle assembly and nuclear pore and nuclear envelope formation. The common
      principle underlying these diverse functions throughout the cell cycle is thought
      to be anisotropy of the distribution of RanGTP (the RanGTP gradient), driven by
      the chromatin-associated guanine nucleotide exchange factor RCC1 (refs 1, 4, 5).
      However, the existence and function of a RanGTP gradient during mitosis in cells
      is unclear. Here we examine the Ran-importin-beta system in cells by conventional
      and fluorescence lifetime microscopy using a biosensor, termed Rango, that
      increases its fluorescence resonance energy transfer signal when released from
      importin-beta by RanGTP. Rango is predominantly free in mitotic cells, but is
      further liberated around mitotic chromatin. In vitro experiments and modelling
      show that this localized increase of free cargoes corresponds to changes in
      RanGTP concentration sufficient to stabilize microtubules in extracts. In cells,
      the Ran-importin-beta-cargo gradient kinetically promotes spindle formation but
      is largely dispensable once the spindle has been established. Consistent with
      previous reports, we observe that the Ran system also affects spindle pole
      formation and chromosome congression in vivo. Our results demonstrate that
      conserved Ran-regulated pathways are involved in multiple, parallel processes
      required for spindle function, but that their relative contribution differs in
      chromatin- versus centrosome/kinetochore-driven spindle assembly systems.

PMID- 16572178
TI  - Retraction: Magnetic carbon.

PMID- 16572177
TI  - Oncogenic activity of Cdc6 through repression of the INK4/ARF locus.
AB  - The INK4/ARF locus encodes three tumour suppressors (p15(INK4b), ARF and
      p16(INK4a)) and is among the most frequently inactivated loci in human cancer.
      However, little is known about the mechanisms that govern the expression of this
      locus. Here we have identified a putative DNA replication origin at the INK4/ARF
      locus that assembles a multiprotein complex containing Cdc6, Orc2 and MCMs, and
      that coincides with a conserved noncoding DNA element (regulatory domain
      RD(INK4/ARF)). Targeted and localized RNA-interference-induced
      heterochromatinization of RD(INK4/ARF) results in transcriptional repression of
      the locus, revealing that RD(INK4/ARF) is a relevant transcriptional regulatory
      element. Cdc6 is overexpressed in human cancers, where it might have roles in
      addition to DNA replication. We have found that high levels of Cdc6 result in
      RD(INK4/ARF)-dependent transcriptional repression, recruitment of histone
      deacetylases and heterochromatinization of the INK4/ARF locus, and a concomitant
      decrease in the expression of the three tumour suppressors encoded by this locus.
      This mechanism is reminiscent of the silencing of the mating-type HM loci in
      yeast by replication factors. Consistent with its ability to repress the INK4/ARF
      locus, Cdc6 has cellular immortalization activity and neoplastic transformation
      capacity in cooperation with oncogenic Ras. Furthermore, human lung carcinomas
      with high levels of Cdc6 are associated with low levels of p16(INK4a). We
      conclude that aberrant expression of Cdc6 is oncogenic by directly repressing the
      INK4/ARF locus through the RD(INK4/ARF) element.

PMID- 16572183
TI  - The burden of prescription coverage of kidney failure patients in the United
      States: is Medicare Part D the answer?

PMID- 16572179
TI  - Retraction: Evidence for spin-charge separation in quasi-one-dimensional organic
      conductors.

PMID- 16572184
TI  - Massive bleeding after biopsy of a renal allograft.

PMID- 16572185
TI  - Non-Pseudomonas Gram-negative peritonitis.
AB  - Non-Pseudomonas Gram-negative organisms account for over 10% of cases of
      peritoneal dialysis-associated peritonitis. The key findings from a paper by
      Szeto et al. are discussed and compared with those from previous publications.
      This type of peritonitis has a high rate of catheter removal and technique
      failure. Results may be better with more aggressive antibiotic treatment. Other
      developments in the field are reviewed.

PMID- 16572187
TI  - Extended release nicotinic acid is a promising agent for phosphate control in
      hemodialysis.

PMID- 16572188
TI  - Fibroblasts in cancer.
AB  - Tumours are known as wounds that do not heal - this implies that cells that are
      involved in angiogenesis and the response to injury, such as endothelial cells
      and fibroblasts, have a prominent role in the progression, growth and spread of
      cancers. Fibroblasts are associated with cancer cells at all stages of cancer
      progression, and their structural and functional contributions to this process
      are beginning to emerge. Their production of growth factors, chemokines and
      extracellular matrix facilitates the angiogenic recruitment of endothelial cells
      and pericytes. Fibroblasts are therefore a key determinant in the malignant
      progression of cancer and represent an important target for cancer therapies.

PMID- 16572189
TI  - Topical lignocaine for vaginismus: a case report.
AB  - Vaginismus is a sexual dysfunction in which spasm of vaginal musculature
      precludes penetrative intercourse. In many cases associated pain or fear of pain
      may contribute to the maintenance of vaginismus. We report a case of primary
      vaginismus with associated pain that benefited from topical application of
      lignocaine gel along with systematic desensitization resulting in successful
      consummation, and suggest that it may be a useful adjunct during finger
      dilatation in the treatment of vaginismus, specifically in patients who have
      associated pain or areas of hyperesthesia in the introitus.

PMID- 16572190
TI  - EIAV vector-mediated delivery of endostatin or angiostatin inhibits angiogenesis
      and vascular hyperpermeability in experimental CNV.
AB  - We evaluated the efficacy of equine infectious anaemia virus (EIAV)-based
      lentiviral vectors encoding endostatin (EIAV.endostatin) or angiostatin
      (EIAV.angiostatin) in inhibiting angiogenesis and vascular hyperpermeability in
      the laser-induced model of choroidal neovascularisation (CNV). Equine infectious
      anaemia virus.endostatin, EIAV.angiostatin or control (EIAV.null) vectors were
      administered into the subretinal space of C57Bl/6J mice. Two weeks after laser
      injury CNV areas and the degree of vascular hyperpermeability were measured by
      image analysis of in vivo fluorescein angiograms. Compared with EIAV.null
      injected eyes, EIAV.endostatin resulted in a 59.5% (P<0.001) reduction in CNV
      area and a reduction in hyperpermeability of 25.6% (P<0.05). Equine infectious
      anaemia virus.angiostatin resulted in a 50.0% (P<0.05) reduction in CNV area and
      a 23.9% (P<0.05) reduction in hyperpermeability. Equine infectious anaemia
      virus.endostatin, but not EIAV.angiostatin significantly augmented the frequency
      of apoptosis within the induced CNV as compared with injected controls. TdT-dUTP
      terminal nick end labeling analysis 5 weeks post-injection, and histological and
      retinal flatmount analysis 12 months post-injection revealed no evidence of
      vector- or transgene expression-related deleterious effects on neurosensory
      retinal cells, or mature retinal vasculature in non-lasered eyes. Highly
      expressing EIAV-based vectors encoding endostatin or angiostatin effectively
      control angiogenesis and hyperpermeability in experimental CNV without long-term
      deleterious effects, supporting the use of such a strategy in the management of
      patients with exudative age-related macular degeneration.

PMID- 16572191
TI  - Acceleration of wound healing by combined gene transfer of hepatocyte growth
      factor and prostacyclin synthase with Shima Jet.
AB  - Although skin diseases are one of the target diseases for gene therapy, there has
      been no practical gene transfer method. First, we examined gene transfer
      efficiency of the spring-powered jet injector, Shima Jet, which was originally
      developed as a non-needle jet injector of insulin. Local gene expression was
      about 100 times higher when the luciferase plasmid was transferred by the Shima
      Jet than by a needle. Gene transfer of beta-galactosidase revealed gene
      expression in the epidermis. Based on these results, we then examined the
      potential of gene therapy using the Shima Jet for wound healing. An increase of
      cellular proliferation of the epidermis and the number of microvessels in the
      granulation tissue was observed after hepatocyte growth factor (HGF) gene
      transfer. An increase in blood flow around the wound was observed after
      prostacyclin synthase (PGIS) gene transfer. Moreover, promotion on wound healing
      was observed in HGF gene transferred group, and further promotion was observed in
      combined gene transferred group as assessed by measuring wound area. These
      results indicate that co-transfer of HGF and PGIS genes by the Shima Jet could be
      an effective strategy to wound healing.

PMID- 16572192
TI  - Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces
      myocardial infarct size in sheep.
AB  - We have recently reported that in pigs with chronic myocardial ischemia heart
      transfection with a plasmid encoding the 165 isoform of human vascular
      endothelial growth factor (pVEGF165) induces an increase in the mitotic index of
      adult cardiomyocytes and cardiomyocyte hyperplasia. On these bases we
      hypothesized that VEGF gene transfer could also modify the evolution of
      experimental myocardial infarct. In adult sheep pVEGF165 (3.8 mg, n=7) or empty
      plasmid (n=7) was injected intramyocardially 1 h after coronary artery ligation.
      After 15 days infarct area was 11.3+/-1.3% of the left ventricle in the VEGF
      group and 18.2+/-2.1% in the empty plasmid group (P<0.02). The mechanisms
      involved in infarct size reduction (assessed in additional sheep at 7 and 10 days
      after infarction) included an increase in early angiogenesis and arteriogenesis,
      a decrease in peri-infarct fibrosis, a decrease in myofibroblast proliferation,
      enhanced cardiomyoblast proliferation and mitosis of adult cardiomyocytes with
      occasional cytokinesis. Resting myocardial perfusion (99mTc-sestamibi SPECT) was
      higher in VEGF-treated group than in empty plasmid group 15 days after myocardial
      infarction. We conclude that plasmid-mediated VEGF gene transfer reduces
      myocardial infarct size by a combination of effects including neovascular
      proliferation, modification of fibrosis and cardiomyocyte regeneration.

PMID- 16572194
TI  - Management in general practice of hypertensive patients poorly controlled with a
      fixed-dose renin-angiotensin system inhibitor and diuretic combination: results
      from a French national survey.
AB  - High rates of uncontrolled hypertensives have been reported in France as well as
      in other countries, partly owing to an inadequate management of hypertension by
      clinicians. The objectives of the study were (1) to describe the therapeutic
      decisions faced by general practitioners (GP) in hypertensives not controlled by
      fixed-dose combination antihypertensive therapy with a renin-angiotensin system
      (RAS) inhibitor and a diuretic (D) and (2) to evaluate the frequency with which
      ambulatory blood pressure monitoring (ABPM) is used in these patients. Each GP
      had to include five uncontrolled hypertensives on fixed-dose RAS inhibitor and D
      combination. A total of 2118 GPs included 9551 patients; 8643 patients were
      receiving at least one of the two drugs at a low dose (group 1) and the remaining
      908 patients were receiving high doses of both drugs (group 2). The most common
      therapeutic choice was that of a new combination, either a fixed-dose in one pill
      or with separate preparations: 65% (n=5621) in group 1 and 56% (n=505) in group
      2. An increase in dose was chosen in 28% of patients in group 1 (n=2467) and
      continuation of treatment without modification in 27% of patients in group 2
      (n=242). A third active principle was only added in 2.5% of patients in group 1
      (n=219) and 11% in group 2 (n=103). Ambulatory blood pressure monitoring was
      employed in 25% of patients (n=2413). An improvement in hypertension management
      should be expected from the implementation of the 2005 French guidelines. Journal
      of Human Hypertension (2006) 20, 407-418. doi:10.1038/sj.jhh.1002000; published
      online 30 March 2006.

PMID- 16572193
TI  - The effect of losartan compared with atenolol on the incidence of
      revascularization in patients with hypertension and electrocardiographic left
      ventricular hypertrophy. The LIFE study.

PMID- 16572195
TI  - Congenital hepatic arteriovenous malformation: an unusual cause of neonatal
      persistent pulmonary hypertension.
AB  - Congenital hepatic arteriovenous malformations are rare anomalies, which
      typically present in infancy with congestive heart failure, anemia, and
      hepatomegaly. Morbidity and mortality is high if the condition is not recognized
      and treated promptly. Hepatic arteriovenous malformation associated with
      persistent pulmonary hypertension of the newborn has been reported in two cases
      in the literature. We report a neonate who was referred for management of
      persistent pulmonary hypertension and was subsequently diagnosed with a large
      hepatic arteriovenous malformation. He underwent coil embolization following
      which pulmonary hypertension resolved.

PMID- 16572196
TI  - Fewer spontaneous arousals during prone sleep in preterm infants at 1 and 3
      months corrected age.
AB  - OBJECTIVE: This study was performed to determine if there were fewer spontaneous
      arousals in prone sleep than in supine sleep. STUDY DESIGN: Home
      polysomnography/video recordings were done during daytime naps in 14 preterm
      infants: four at corrected age of 1 month, nine at both 1 and 3 months, and one
      only at 3 month. A body movement lasting 3 to 60 s during sleep was used as an
      indicator of spontaneous arousals. RESULTS: Most arousals had a heart rate
      increase and change in respiration pattern. The mean duration of the intervals
      between successive arousals in active and quiet sleep was significantly longer in
      prone at 1 and 3 months of age. The duration of arousals was significantly
      shorter at 3 months corrected age compared with one month corrected age during
      active sleep. The duration of arousals was shorter during quiet sleep at one
      month compared with active sleep. CONCLUSION: There were fewer spontaneous
      arousals that is, longer interval between successive arousals in prone, which
      may, in part, explain the increase in risk of Sudden Infant Death Syndrome.

PMID- 16572198
TI  - A quantitative assay for JAK2(V617F) mutation in myeloproliferative disorders by
      ARMS-PCR and capillary electrophoresis.
AB  - A point mutation in the Janus tyrosine kinase 2 (JAK2) gene has been described in
      patients with chronic myeloproliferative disorders (MPD), but the clinical
      significance of JAK2(V617F), which may be harbored in either the heterozygote or
      homozyote status, is still largely undefined. There are indirect suggestions that
      clinical phenotype and also some biological characteristics are dependent on the
      mutated allele levels. We have designed and validated in 179 MPD patients an
      amplification-refractory mutation sequencing PCR assay that allows the relative
      quantitation of mutated and normal JAK2 mRNAs using dye-labelled mutation
      specific primers and capillary electrophoresis. Direct sequencing confirmed the
      specificity of the assay, which has a detection limit congruent with1% and
      allowed to identify 9% more JAK2-mutated patients as compared to conventional
      allele-specific PCR. The mutated mRNA ratio ranged from 5 to 51% in the
      JAK2(V617F) heterozygote and from 45 to 100% in the homozygote patients.
      Expression levels of both PRV-1 and NF-E2 gene, previously found to be
      overexpressed in MPD patients, were significantly correlated to the amount of
      mutated JAK2 mRNA. We propose that this method might complement current
      technologies based on genomic DNA analysis, and lead prospectively to a better
      clinically oriented assessment of the impact of JAK2(V617F) mutation in MPD.

PMID- 16572197
TI  - MLL rearrangements emerge during spontaneous apoptosis of clinical blood samples.

PMID- 16572199
TI  - Upregulation of Bfl-1/A1 in leukemia cells undergoing differentiation by all
      trans retinoic acid treatment attenuates chemotherapeutic agent-induced
      apoptosis.
AB  - All-trans retinoic acid (ATRA) induces differentiation of NB4 and HL-60 leukemia
      cells, but not R4 and HL-60/Res cells. Three agents used in cancer therapy,
      doxorubicin (Dox), arsenic trioxide (As(2)O(3)) and paclitaxel, induce apoptosis,
      but not differentiation, in all of these cell lines. The induction of apoptosis
      by these agents is decreased in ATRA-pretreated NB4 and HL-60 cells, but not in
      ATRA-pretreated R4 and HL-60/Res cells. The level of Bcl-2 protein is decreased
      by ATRA treatment in NB4, HL-60 and HL-60/Res cells. The level of Mcl-1 protein
      is increased by ATRA treatment in NB4 and R4 cells, but not in HL-60 and HL
      60/Res cells. Bfl-1/A1 mRNA is not expressed in these cell lines, however, its
      expression is markedly induced by ATRA treatment in NB4 and HL-60 cells, but not
      in R4 or HL-60/Res cells, which correlates with inhibition of apoptosis.
      Inhibiting Bfl-1/A1 mRNA upregulation in ATRA-pretreated NB4 cells using small
      interfering RNA (siRNA) partly recovers cell sensitivity to Dox-induced
      apoptosis. These data demonstrate that ATRA induction of Bfl-1/A1 in
      differentiated NB4 and HL-60 cells contributes to a loss of sensitivity to
      chemotherapy-induced apoptosis.

PMID- 16572200
TI  - The lack of association between JAK2 V617F mutation and myelodysplastic syndrome
      with or without myelofibrosis.

PMID- 16572201
TI  - Inactivation of p53 and deletion of ATM in B-CLL patients in relation to IgVH
      mutation status and previous treatment.

PMID- 16572202
TI  - t(5;12)(q23-31;p13) with ETV6-ACSL6 gene fusion in polycythemia vera.

PMID- 16572203
TI  - Epigenetic disruption of two proapoptotic genes MAPK10/JNK3 and PTPN13/FAP-1 in
      multiple lymphomas and carcinomas through hypermethylation of a common
      bidirectional promoter.

PMID- 16572204
TI  - Molecular pathogenesis of MALT lymphoma: two signaling pathways underlying the
      antiapoptotic effect of API2-MALT1 fusion protein.
AB  - At least three recurrent chromosomal translocations, t(11;18)(q21;q21),
      t(1;14)(p22;q32), t(14;18)(q32;q21), involving the API2-MALT1 fusion protein,
      BCL10 and MALT1, have been implicated in the pathogenesis of mucosa-associated
      lymphoid tissue (MALT) lymphoma. Several lines of evidence indicated that both
      BCL10 and MALT1 are required for nuclear factor kappa B (NF-kappaB) activation by
      antigen receptor stimulation in lymphocytes, and API2-MALT1 can bypass this
      BCL10/MALT1 signaling pathway. Nuclear factor kappa B activation may contribute
      to antiapoptotic effect through NF-kappaB-mediated upregulation of apoptotic
      inhibitor genes. We recently demonstrated that API2-MALT1 can induce
      transactivation of the API2 gene through NF-kappaB activation, thus highlighting
      a positive feedback-loop mechanism of self-activation by upregulating its own
      expression in t(11;18) MALT lymphomas. We also demonstrated that API2-MALT1
      possesses an antiapoptotic effect, in part, through its direct interaction with
      apoptotic regulators. These findings therefore led us to hypothesize that the
      antiapoptotic effect by API2-MALT1 may be mediated by its interaction with
      apoptotic regulators, on the one hand, and by NF-kappaB-mediated upregulation of
      apoptotic inhibitor genes on the other. We also found that BCL10 and MALT1 are
      shuttling between nucleus and cytoplasm, and that MALT1 can regulate the
      subcellular location of BCL10.

PMID- 16572206
TI  - HOXA cluster deregulation in T-ALL associated with both a TCRD-HOXA and a CALM
      AF10 chromosomal translocation.

PMID- 16572205
TI  - BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem
      cells by CrkL phosphorylation status using flow cytometry.
AB  - In chronic myeloid leukaemia, CD34(+) stem/progenitor cells appear resistant to
      imatinib mesylate (IM) in vitro and in vivo. To investigate the underlying
      mechanism(s) of IM resistance, it is essential to quantify Bcr-Abl kinase status
      at the stem cell level. We developed a flow cytometry method to measure CrkL
      phosphorylation (P-CrkL) in samples with <10(4) cells. The method was first
      validated in wild-type (K562) and mutant (BAF3) BCR-ABL(+) as well as BCR-ABL(-)
      (HL60) cell lines. In response to increasing IM concentration, there was a linear
      reduction in P-CrkL, which was Bcr-Abl specific and correlated with known
      resistance. The results were comparable to those from Western blotting. The
      method also proved to be reproducible with small samples of normal and Ph(+)
      CD34(+) cells and was able to discriminate between Ph(-), sensitive and resistant
      Ph(+) cells. This assay should now enable investigators to unravel the
      mechanism(s) of IM resistance in stem cells.

PMID- 16572207
TI  - Where are the biologists?

PMID- 16572208
TI  - A one-step protocol for the chemical derivatisation of glass microfluidic
      devices.
AB  - A simple and robust derivatisation system for glass and silica microdevices is
      described. The device surface is coated in a one-step treatment with a highly
      cross-linked polystyrene/divinylbenzene/allylsiloxane copolymer. The surface
      derivatisation is highly resistant to solvents, acids, bases and oxidising or
      reducing agents.

PMID- 16572209
TI  - Miniaturised isotachophoresis analysis.
AB  - The application of miniaturized total analysis systems (microTAS) has seen rapid
      development over the past few years. Isotachophoresis (ITP) has been transferred
      into microchip format for both electrophoretic separation and pretreatment
      purposes, due to its advantageous features including separation parameters
      controlled by electrolyte composition and high sample load capacity. The primary
      focus of this concise review is to summarize the basic features of microchip
      based ITP and its applications to the analysis and pretreatment of ionic
      compounds and biomolecules that have arisen since 1998.

PMID- 16572210
TI  - On-chip extrusion of lipid vesicles and tubes through microsized apertures.
AB  - In this work we present the formation of micrometre-sized lipid vesicles and
      tubes with perfectly homogeneous diameter and extraordinary length. The method is
      a novel approach for unconventional fabrication of soft-matter microstructured
      devices based on the combination of top-down and bottom-up fabrication processes.
      Photolithography techniques are applied to fabricate microsized apertures that
      provide the requirements to form lipid structures with predictable size and to
      align and guide the vesicles and tubes in microstructured channels. The formation
      is facilitated by self-assembly of polar lipids to a lipid membrane that is
      afterwards forced to undergo a shape transformation by extrusion through a
      microsized aperture. Both the geometrical restriction by the small aperture and
      the pressure difference between the top and bottom sides of the aperture
      determine the form and length of the vesicles and tubes. A strong pressure
      difference favors the formation of lipid tubes, while a low pressure difference
      results in the formation of vesicle bunches with spherical and cylindrical
      shapes. Potential applications for the formed lipid structures could be as
      microreactors and transport channels as well as in the construction of flexible
      microfluidic networks.

PMID- 16572211
TI  - X-ray microfocussing combined with microfluidics for on-chip X-ray scattering
      measurements.
AB  - This work describes the fabrication of thin microfluidic devices in Kapton
      (polyimide). These chips are well-suited to perform X-ray scattering experiments
      using intense microfocussed beams, as Kapton is both relatively resistant to the
      high intensities generated by a synchrotron, and almost transparent to X-rays. We
      show networks of microchannels obtained using laser ablation of Kapton films, and
      we also present a simple way to perform fusion bonding between two Kapton films.
      The possibilities offered using such devices are illustrated with X-ray
      scattering experiments. These experiments demonstrate that structural
      measurements in the 1 A-20 nm range can be obtained with spatial resolutions of a
      few microns in a microchannel.

PMID- 16572212
TI  - Flow-induced deformation of shallow microfluidic channels.
AB  - We study the elastic deformation of poly(dimethylsiloxane) (PDMS) microchannels
      under imposed flow rates and the effect of this deformation on the laminar flow
      profile and pressure distribution within the channels. Deformation is
      demonstrated to be an important consideration in low aspect ratio (height to
      width) channels and the effect becomes increasingly pronounced for very shallow
      channels. Bulging channels are imaged under varying flow conditions by confocal
      microscopy. The deformation is related to the pressure and is thus non-uniform
      throughout the channel, with tapering occurring along the stream-wise axis. The
      measured pressure drop is monitored as a function of the imposed flow rate. For a
      given pressure drop, the corresponding flow rate in a deforming channel is found
      to be several times higher than expected in a non-deforming channel. The
      experimental results are supported by scaling analysis and computational fluid
      dynamics simulations coupled to materials deformation models.

PMID- 16572213
TI  - Quantitative modeling of dielectrophoretic traps.
AB  - We present quantitative modeling software for simulating multiple forces acting
      on a single particle in a microsystem. In this paper, we focus on
      dielectrophoretic (DEP) trapping of single cells against fluid flow. The software
      effectively models the trapping behavior for a range of particles including
      beads, mammalian cells, viruses, and bacteria. In addition, the software can be
      used to reveal useful information about the DEP traps - such as multipolar DEP
      force effects, trap size-selectivity, and effects from varying the flow chamber
      height. Our modeling software thus serves as a predictive tool, enabling the
      design of novel DEP traps with superior performance over existing trap
      geometries. In addition, the software can evaluate a range of trap dimensions to
      determine the effects on trapping behavior, thus optimizing the trap geometry
      before it is even fabricated. The software is freely available to the scientific
      community at: .

PMID- 16572214
TI  - Methods to electrophoretically stretch DNA: microcontractions, gels, and hybrid
      gel-microcontraction devices.
AB  - The ability to controllably and continuously stretch large DNA molecules in a
      microfluidic format is important for gene mapping technologies such as Direct
      Linear Analysis (DLA). We have recently shown that electric field gradients can
      be readily generated in a microfluidic device and the resulting field is purely
      elongational. We present a single molecule fluorescence microscopy analysis of T4
      DNA (169 kbp) stretching in the electric field gradients in a hyperbolic
      contraction microchannel. In addition, we are able to selectively pattern a
      crosslinked gel anywhere inside the microchannel. With an applied electric field,
      DNA molecules are forced to reptate through the gel and they moderately stretch
      as they exit the gel. By placing a gel immediately in front of the hyperbolic
      contraction, we bypass "molecular individualism" and achieve highly uniform and
      complete stretching of T4 DNA.

PMID- 16572215
TI  - Reversible thermo-responsive sieving matrix for oligonucleotide separation.
AB  - A reversible thermo-responsive gel system, consisting of Pluronic copolymer
      mixture of F87 and F127, has been used to successfully carry out the separation
      of oligonucleotides, for the first time, by microchip-based capillary
      electrophoresis. Pluronic triblock copolymers F87 (E(61)P(40)E(61)) and F127
      (E(99)P(69)E(99)), with E, P, and subscript denoting oxyethylene, oxypropylene,
      and segment length respectively, have a unique temperature dependent viscosity
      adjustable property and a dynamic coating ability in aqueous solution, including
      1 x TBE buffer. The mixture solution has a reversible thermo-responsive property
      and its sol-gel transition temperature can be adjusted ranging from about 17
      degrees C to 38 degrees C by varying the relative weight ratio of F87 and F127 at
      an optimized concentration of approximately 30% (w/v) for oligonucleotide
      separations. Oligonucleotide sizing markers ranging from 8 to 32 base could be
      successfully separated in a 1.5 cm long separation channel by the mixture
      solution in its gel-like state. A 30% (w/v) with a F87/F127 weight ratio of 1
      ratio 2 which has a "sol-gel" transition point of about 26 degrees C shows the
      best sieving ability. The sieving ability of the mixture solution was further
      confirmed in an Agilent Bioanalyzer 2100 system. Fast separation of
      oligonucleotides has been achieved within 40 s with one base resolution.

PMID- 16572216
TI  - Zeolite nanoparticle modified microchip reactor for efficient protein digestion.
AB  - An enzymatic microreactor has been fabricated based on the poly(methyl
      methacrylate) (PMMA) microchchip surface-modified with zeolite nanoparticles. By
      introducing the silanol functional groups, the surface of PMMA microchannel has
      been successfully modified with silicalite-1 nanoparticle for the first time due
      to its large external surface area and high dispersibility in solutions. Trypsin
      can be stably immobilized in the microchannel to form a bioreactor using silica
      sol-gel matrix. The immobilization of enzyme can be realized with a stable gel
      network through a silicon-oxygen-silicon bridge via tethering to those silanol
      groups, which has been investigated by scanning electron microscopy and microchip
      capillary electrophoresis with laser-induced fluorescence detection. The maximum
      proteolytic rate constant of the immobilized trypsin is measured to be about 6.6
      mM s(-1). Using matrix assisted laser desorption and ionization time-of-flight
      mass spectrometry, the proposed microreactor provides an efficient digestion of
      cytochrome c and bovine serum albumin at a fast flow rate of 4.0 microL min(-1),
      which affords a very short reaction time of less than 5 s.

PMID- 16572217
TI  - Toolbox for the design of optimized microfluidic components.
AB  - A computational "toolbox" for the a priori design of optimized microfluidic
      components is presented. These components consist of a microchannel under low
      Reynolds number, pressure-driven flow, with an arrangement of grooves cut into
      the top and bottom to generate a tailored cross-channel flow. An advection map
      for each feature (i.e., groove of a particular shape and orientation) predicts
      the lateral transport of fluid within the channel due to that feature. We show
      that applying these maps in sequence generates an excellent representation of the
      outflow distribution for complex designs that combine these basic features. The
      effect of the complex three-dimensional flow field can therefore be predicted
      without solving the governing flow equations through the composite geometry, and
      the resulting distribution of fluids in the channel is used to evaluate how well
      a component performs a specified task. The generation and use of advection maps
      is described, and the toolbox is applied to determine optimal combinations of
      features for specified mixer sizes and mixing metrics.

PMID- 16572218
TI  - AC electroosmotic micromixer for chemical processing in a microchannel.
AB  - A rapid micromixer of fluids in a microchannel is presented. The mixer uses AC
      electroosmotic flow, which is induced by applying an AC voltage to a pair of
      coplanar meandering electrodes configured in parallel to the channel. To
      demonstrate performance of the mixer, dilution experiments were conducted using a
      dye solution in a channel of 120 microm width. Rapid mixing was observed for flow
      velocity up to 12 mm s(-1). The mixing time was 0.18 s, which was 20-fold faster
      than that of diffusional mixing without an additional mixing mechanism. Compared
      with the performance of reported micromixers, the present mixer worked with a
      shorter mixing length, particularly at low Peclet numbers (Pe < 2 x 10(3)).

PMID- 16572220
TI  - Continuous flow separation of particles within an asymmetric microfluidic device.
AB  - A microfluidic based device has been developed for the continuous separation of
      polymer microspheres, taking advantage of the flow characteristics of systems.
      The chip consists of an asymmetric cavity with variable channel width which
      enables continuous amplification of the particle separation for different size
      particles within the laminar flow profile. The process has been examined by
      varying the sample inlet position, the sample to media flow rate ratio, and the
      total flow rate. This technique can be applied for manipulating both microscale
      biological and colloidal particles within microfluidic systems.

PMID- 16572219
TI  - Enzymatically-generated fluorescent detection in micro-channels with internal
      magnetic mixing for the development of parallel microfluidic ELISA.
AB  - The Enzyme-Linked Immuno-Sorbent Assay, or ELISA, is commonly utilized to
      quantify small concentrations of specific proteins for a large variety of
      purposes, ranging from medical diagnosis to environmental analysis and food
      safety. However, this technique requires large volumes of costly reagents and
      long incubation periods. The use of microfluidics permits one to specifically
      address these drawbacks by decreasing both the volume and the distance of
      diffusion inside the micro-channels. Existing microfluidic systems are limited by
      the necessary control of extremely low flow rates to provide sufficient time for
      the molecules to interact with each other by diffusion only. In this paper, we
      describe a new microfluidic design for the realization of parallel ELISA in stop
      flow conditions. Magnetic beads were used both as a solid phase to support the
      formation of the reactive immune complex and to achieve a magnetic mixing inside
      the channels. In order to test the detection procedure, the formation of the
      immune complex was performed off-chip before the reactive beads were injected
      into the reaction chamber. Anti-streptavidin antibodies were quantified with low
      picomolar sensitivity (0.1-6.7 pM), a linear range of 2 orders of magnitude and
      good reproducibility. This work represents the first step toward a new platform
      for simple, highly effective and parallel microfluidic ELISA.

PMID- 16572221
TI  - Steady flow generation in microcirculatory systems.
AB  - In this paper we explore the mechanical generation of steady-non pulsatile-flow
      in microfluidic systems. The rationale of the paper is inspired in the example of
      cardiovascular systems where at the microscale (i.e. capillaries) the flow is
      steady rather than pulsatile to optimize performance. We present a solution to
      the generation of steady flow in engineered microfluidic systems either in open
      or closed loop configurations via the use of disc pumps. The disc pump consists
      of a flat rotating disc and utilizes both viscous drag and centrifugal force to
      achieve pumping. Experiments using single loop and double loop microfluidic
      systems are presented to characterize the disc pump. Continuous flow generated by
      the disc pumps can be used to separate particles based on size using
      recirculating loops and for extraction of small particles without disturbing the
      concentration of bigger particles. The potential impact of this technology
      includes sample separation and extraction techniques into portable microfluidic
      labs-on-a-chip, and long term culture systems for cells in suspension.

PMID- 16572222
TI  - Capillary inserts in microcirculatory systems.
AB  - Microfluidic loops (i.e. closed fluid paths) pose specific practical challenges
      such as priming, introducing analytes or reagents in a controlled way and
      sampling products. In this technical note we address these three issues using a
      removable part of the microchannel that we call a 'capillary insert'.

PMID- 16572223
TI  - Reliable fabrication method of transferable micron scale metal pattern for
      poly(dimethylsiloxane) metallization.
AB  - We have developed a reliable fabrication method of forming micron scale metal
      patterns on poly(dimethylsiloxane) (PDMS) using a pattern transfer process. A
      metal stack layer consisting of Au-Ti-Au layers, providing a weak but reliable
      adhesion, was deposited on a silicon wafer. The metal stack layer was then
      transferred to a PDMS substrate using serial and selective etching. We
      demonstrate that features as small as 2 microm were reliably transferred on to
      the PDMS substrate for use as interconnects and electrodes for biosensors and
      flexible electronics application.

PMID- 16572225
TI  - Recent developments in enzymatic chlorination.
AB  - While the existence of chlorinated natural products has been known for over 100
      years, our understanding of the enzymology of biological chlorination reactions
      has been limited to chloroperoxidases, which are now known not to play a
      significant role in chlorometabolite biosynthesis. The discoveries of new classes
      of halogenases, described in this Highlight, have shed new light on the
      mechanisms of enzymatic chlorination of aromatic and aliphatic compounds.

PMID- 16572226
TI  - Marine chemical ecology.
AB  - This review covers the recent marine chemical ecology literature for
      phytoplankton, macroalgae, sponges and other benthic invertebrates; 249
      references are cited.

PMID- 16572227
TI  - Acetylcholinesterase inhibitors from plants and fungi.
AB  - This review describes 183 compounds obtained from plants and fungi which have
      been shown to inhibit acetylcholinesterase. The mechanism of action of
      cholinesterase, together with the binding sites, and, where this is known, the
      mode of action of inhibitors is described. The relative activities of the
      different compounds are recorded. The strongest inhibitors are generally
      alkaloids although some meroterpenoids from fungi have also been found to be
      active and display better selectivity.

PMID- 16572229
TI  - The nature and role of pigments of marine invertebrates.
AB  - Marine animals, especially those from tropical waters, are often brilliantly
      coloured, and bright colouration is widespread in both sessile and non-sessile
      invertebrates. These spectacular natural colours are common in species inhabiting
      shallow waters, and appear not only in animals exposed to bright light, but also
      in those living in dark areas where colours are visible only with artificial
      illumination. Marine organisms also show variation in colour with depth and
      geographical location, and display great variety in colour patterning. These
      colour characteristics are the result of several different processes, and serve
      various purposes - the distribution and function of pigments seems to vary
      between invertebrate groups. In addition to playing an important role in how
      marine organisms interact, pigments may be involved in physiological processes.
      Although nitrogenous pigments predominate, marine organisms contain pigments
      belonging to all the major structural classes of natural products, as well as
      some that are unique to the marine environment. This review discusses the nature
      and significance of such pigments, the chemical and biological processes
      involved, the factors responsible for and affecting bright colourations, as well
      as their evolution and speculation as to their function.

PMID- 16572228
TI  - Saxitoxin, a toxic marine natural product that targets a multitude of receptors.
AB  - Saxitoxin (STX) was discovered early last century and can contaminate seafood and
      drinking water, and over time has become an invaluable research tool and an
      internationally regulated chemical weapon. Among natural products, toxins obtain
      a unique reputation from their high affinity and selectivity for their target
      pharmacological receptor, which for STX has long been considered to only be the
      voltage gated sodium channel. In recent times however, STX has been discovered to
      also bind to calcium and potassium channels, neuronal nitric oxide synthase, STX
      metabolizing enzymes and two circulatory fluid proteins, namely a transferrin
      like family of proteins and a unique protein found in the blood of pufferfish.

PMID- 16572230
TI  - The biosynthesis, molecular genetics and enzymology of the polyketide-derived
      metabolites.
AB  - This review covers the biosynthesis of aliphatic and aromatic polyketides as well
      as mixed polyketide/NRPS metabolites, and discusses the molecular genetics and
      enzymology of the proteins responsible for their formation.

PMID- 16572231
TI  - Spongian diterpenoids from marine sponges.
AB  - This review presents the structure, biological activity and, where applicable,
      references to the syntheses of 154 spongian and rearranged spongian diterpenoids
      isolated from marine sponges of the orders Dictyoceratida and Dendroceratida.
      There have been no studies of the biosynthesis of either spongian diterpenoids or
      their rearranged derivatives reported in the literature. The potential
      chemotaxonomic significance of spongian and rearranged spongian ditepenoids is
      discussed.

PMID- 16572232
TI  - Thinking in schizophrenia: perspectives from community clinic to neural
      circuitry.

PMID- 16572233
TI  - Judicious use of antibiotics in paediatric infections: issues and challenges.

PMID- 16572234
TI  - Prescribing patterns among paediatric inpatients in a teaching hospital in
      western Nepal.
AB  - INTRODUCTION: Infants and children constitute a large proportion of the
      population in developing countries. In Nepal, studies on drug use patterns in the
      paediatric age group are lacking in hospitals in the western region. The present
      study was carried out to obtain demographical information and information on the
      prescribing patterns of drugs. The antibiotic sensitivity patterns of commonly
      isolated micro-organisms and the mean cost of drugs were obtained. METHODS: The
      study was carried out over a four-month period (December 1, 2003 to March 31,
      2004) at the Manipal Teaching Hospital, a tertiary care hospital in Pokhara,
      western Nepal. The case records of patients discharged from the paediatrics ward
      during the study period were analysed. Mean number of drugs prescribed was
      calculated. The percentage of admissions that were prescribed antibiotics was
      determined. RESULTS: 356 patients were admitted during the study period, of which
      228 were male. The median duration of hospitalisation was four days. The mean
      number of drugs prescribed per admission was 4.5. 789 drugs (48.9 percent) were
      prescribed by the parenteral route. Antibiotics were prescribed in 249 admissions
      (69.9 percent). Staphylococcus aureus, Escherichia coli, and Acinetobacter
      species were the common organisms isolated, and were resistant in some cases to
      the commonly-used antibiotics. The mean (+/- standard deviation) cost of drugs
      per admission was 5.4 (+/-1.6) US dollars. CONCLUSION: Prescribing by generic
      name should be encouraged. Use of parenteral antibiotics was high and route
      conversion programmes should be instituted. Use of antibiotics for predominantly
      viral infections should be reduced. Treatment guidelines for common conditions
      should be formulated.

PMID- 16572235
TI  - Parental knowledge, attitudes and antibiotic use for acute upper respiratory
      tract infection in children attending a primary healthcare clinic in Malaysia.
AB  - INTRODUCTION: A study was carried out in a primary healthcare clinic in the Hulu
      Langat district of Malaysia to assess the parental knowledge, attitudes and
      antibiotic use for common childhood acute upper respiratory tract infection
      (URTI). METHODS: A cross-sectional study involving 421 parents, who were surveyed
      by using an interviewer-administered questionnaire, from April to June 2001.
      RESULTS: Approximately 59 percent of parents from this study believed that
      weather was the main cause of acute URTI of their children, 13 percent thought it
      was due to food, and only about 27 percent said it was caused by germs. Nearly 68
      percent, 69 percent and 76 percent of them believed that antibiotics was helpful
      in treating the common cold, cough and fever, respectively. 29 percent of parents
      who thought that their child with acute URTI needed antibiotics were not
      prescribed with any. On the other hand, 17 percent believed that antibiotics were
      unnecessary when prescribed. 28 percent of parents had requested for antibiotics,
      and 93 percent received what they requested for their child with acute URTI.
      About 31 percent of parents who did not request any antibiotics claimed that
      private general practitioners habitually prescribed antibiotics. The antibiotic
      compliance was poor with only 74 percent completing the entire course, with 85
      percent of them stopping once they improved symptomatically. 15 percent of
      parents gave "leftover" antibiotics, 24 percent gave "shared" antibiotics, and
      5.5 percent bought antibiotics for their child with acute URTI without consulting
      a doctor. CONCLUSION: This study shows that parents often have inadequate
      knowledge and misconceptions on antibiotic use for acute URTI in children.
      Improved parental education may reduce unnecessary antibiotic prescription and
      antimicrobial resistance in the community.

PMID- 16572236
TI  - Comparative study of bacteriology in recurrent tonsillitis among children and
      adults.
AB  - INTRODUCTION: Diagnosis and treatment of acute tonsillitis are one of the most
      common problems seen at an otorhinolaryngology clinic in both adult and
      paediatric populations. Much has been written about bacteriology of recurrent
      tonsillitis but it remains a controversial topic. Despite the fact that
      tonsillitis is so common, consensus seems to be lacking as to the main causative
      organism and the differences between children and adults. The tonsillar core
      bacteriology of 233 patients with recurrent tonsillitis who underwent
      tonsillectomy from January 2000 to June 2003 is presented. METHODS: The patient
      population was divided into two groups, namely: the paediatric group and the
      adult group. 132 patients, whose age was more than 12 years, were in the adult
      group. 101 patients aged between two and 12 years, were in the paediatric group.
      The bacteriology of the children and adults were tabulated according to their
      species, and were compared. RESULTS: 138 patients grew single pathogenic bacteria
      in their tonsillar core culture, 52 grew two different pathogenic bacteria, and
      the rest (43) grew normal bacterial flora. Staphylococcus aureus was the most
      commonly-isolated bacterium and accounted for 40.9 percent of the total cultures
      isolated; its prevalence was the same in the adults and children. Beta-haemolytic
      Streptococcus was isolated in 23 percent of subjects, and was predominantly from
      group A (Streptococcus pyogens). Group A beta-haemolytic Streptococci was more
      prevalent in children. Pseudomonas aeruginosa, which rarely cause pathogenicity
      in tonsils, was cultured from nine (3.8 percent) of our study subjects.
      CONCLUSION: This study showed that Staphylococcus aureus is the most common
      pathogenic bacteria cultured both in adults and children. Klebsiella pneumonia,
      Streptococcus pneumonia, Escherichia coli and Enterobacter are more prevalent in
      adults. Haemophilus influenza and Streptococcus pyogens are more prevalent in
      children. Pseudomonas aeruginosa is not a rare causative organism in recurrent
      tonsillitis. Since the mechanism of activation of infection in recurrent
      tonsillitis is unknown, knowing the bacteriology does not help us to treat the
      disease. However, it may be a stepping stone to eventually understanding whether
      the bacteria play a role in reactivating recurrent infections. From previous and
      current studies, there is no relationship between bacteriology and recurrent
      infections.

PMID- 16572237
TI  - Predictors of serious bacterial infection in children aged 3 to 36 months with
      fever without source.
AB  - INTRODUCTION: Children commonly present with fever without source yet there is no
      reliable and consistent method of identifying those at risk of serious bacterial
      infection. In this study, we sought to identify predictors of serious bacterial
      infection in children aged between three to 36 months with fever without source.
      METHODS: Inpatient records of all children aged three to 36 months admitted from
      the Emergency Department of Singapore's main paediatric hospital between October
      2001 to February 2002 with International Classification of Diseases (ninth
      revision) diagnosis codes 038 (septicaemia), 079 (viral fever), or 780 (pyrexia
      of unknown origin), were retrieved and reviewed. Patients identified as having
      fever without source were enrolled. RESULTS: Of 86 enrolled children, 17 (19.8
      percent) had serious bacterial infection. Duration of fever and white blood cell
      count were found to be significant predictors. Children with white blood cell
      count equal to or greater than 16,000/cubic mm had 6.9 times (95 percent
      confidence interval [CI] is 1.7 to 28.4) increased risk of serious bacterial
      infection, while children with fever of duration exceeding three days before
      presentation had 3.8 times (95 percent CI is 1.1 to 13.1) increased risk of
      serious bacterial infection. A combination of white blood cell count less than
      16,000/cubic mm and duration of fever three days or less had a negative
      predictive value of 1.0 (95 percent CI is 0.88 to 1.0) and a sensitivity of 1.0
      (95 percent CI is 0.82 to 1.0). CONCLUSION: The two identified predictors offer
      an estimate of the risk of serious bacterial infection in children aged three to
      36 months with fever without source.

PMID- 16572238
TI  - Frequency and susceptibility profile of pathogens causing urinary tract
      infections at a tertiary care hospital in western Nepal.
AB  - INTRODUCTION: Urinary tract infection (UTI) is the most common nosocomial
      infection among hospitalised patients. Area-specific monitoring studies aimed to
      gain knowledge about the type of pathogens responsible for UTIs and their
      resistance patterns may help the clinician to choose the correct empirical
      treatment. Recent reports have shown increasing resistance to commonly-used
      antibiotics. We aimed to study the antibiotic resistance pattern of the urinary
      pathogens isolated from hospitalised patients. METHODS: Three urine samples were
      collected by the mid-stream "clean catch" method from 1,680 clinically-suspected
      cases of urinary tract infections from inpatients of various clinical departments
      during one year. The samples were tested microbiologically by standard
      procedures. Antibiotic susceptibility of the isolated pathogens was tested for
      commonly-used antibiotics by Kirby-Bauer technique according to NCCLS guidelines.
      RESULTS: Significant bacteriuria was present in 71.7 percent of the samples, 17
      percent were sterile, 4.8 percent showed insignificant bacteriuria, and 6.5
      percent non-pathogenic bacteriuria. The most common pathogens isolated were
      Escherichia coli (59.4 percent), Klebsiella spp (15.7 percent) and Enterococcus
      faecalis (8.1 percent). The mean susceptibility was high for amikacin (87.2
      percent), ciprofloxacin (74.8 percent), ceftazidime (71.5 percent) and gentamicin
      (70.4 percent) but low for nitrofurantoin (35 percent), cephalexin (49.7 percent)
      and ampicillin (50.5 percent). Escherichia coli was found to be most susceptible
      to amikacin (98 percent) followed by gentamicin (87.9 percent), ceftazidime (80.8
      percent), norfloxacin (78.4 percent) and cotrimoxazole (77.9 percent).
      CONCLUSION: A high isolation rate of pathogens from urine samples of clinically
      suspected UTI shows a good correlation between clinical findings and
      microbiological methods. The antibiotics commonly used in UTIs are less
      effective. Since the present study was a cross-sectional study, regular
      monitoring is required to establish reliable information about resistance pattern
      of urinary pathogens for optimal empirical therapy of patients with nosocomial
      UTIs.

PMID- 16572239
TI  - Immunogenicity and reactogenicity of a reduced-antigen-content diphtheria-tetanus
      acellular pertussis vaccine as a single-dose booster in Singaporean adults.
AB  - INTRODUCTION: Older children and adults, susceptible to pertussis because of
      waning immunity, may serve as a reservoir of infection, leading to severe disease
      among young unvaccinated infants. Booster diphtheria-tetanus-acellular pertussis
      (dTpa) vaccination in older age groups is rare in Singapore, one reason being the
      increase in reactogenicity with each successive dose. The aim of this study was
      to assess the immunogenicity, safety and reactogenicity of a reduced antigen,
      combined dTpa vaccine as a single booster dose in healthy adults aged 18 years or
      older. METHODS: A total of 150 healthy adults, 18 to 60 years of age, received a
      single dose of GlaxoSmithKline Biologicals' dTpa vaccine with reduced content for
      diphtheria and pertussis, with measurement of pre- and post-vaccination antibody
      titres. RESULTS: Prior to vaccination, 71.6 percent and 92.6 percent of the
      subjects had anti-diphtheria and anti-tetanus antibody levels greater than or
      equal to 0.1 IU/mL, respectively. 46.7 percent, 98.5 percent and 44.4 percent of
      subjects were seropositive for pertussis toxin (PT), filamentous haemagglutinin
      (FHA) and pertactin (PRN) antibodies, respectively. One month after vaccination,
      there was an increase in geometric mean titres from pre-vaccination to post
      vaccination blood samples for anti-diphtheria (greater than seven-fold), anti
      tetanus (greater than five-fold), anti-PT (greater than 11-fold), anti- FHA
      (greater than 25-fold) and anti-PRN (greater than 31-fold) antibodies. Solicited
      grade three local symptoms (pain, redness and swelling) were reported in 14.1
      percent, 8.1 percent and 10.4 percent of subjects, respectively. No serious
      adverse events were reported. CONCLUSION: In summary, the dTpa vaccine is
      immunogenic, safe and well-tolerated in Singaporean adults.

PMID- 16572240
TI  - Prevalence study to elucidate the transmission pathways of Helicobacter pylori at
      oral and gastroduodenal sites of a South Indian population.
AB  - INTRODUCTION: Since the discovery of Helicobacter pylori (H. pylori), much
      progress has been made worldwide in the field of its epidemiology. In spite of
      these advancements, many aspects of epidemiology still remain unclear,
      particularly among populations with low socio-economic status. The present study
      was designed to elucidate the different routes of transmission of H. pylori in
      the Hyderabad (South India) population and to investigate the impact of certain
      factors, such as age, gender, and lifestyle. METHODS: Samples used for the study
      included saliva and biopsy samples of 400 symptomatic subjects from Hyderabad,
      India. The patients were retrospectively grouped, based on histopathology of the
      biopsy and 16S rRNA amplification of both saliva and biopsy as H. pylori positive
      and negative. RESULTS: This study showed that the prevalence of H. pylori in both
      saliva and biopsy samples increased with age. In addition, the H. pylori
      infection was found more commonly in the saliva and biopsy samples among males
      (64 percent and 60 percent, respectively) than females (53.3 percent and 64
      percent, respectively). Similarly, 71.6 percent and 73.5 percent of those who
      consumed municipal water acquired H. pylori (which were respectively found in
      their saliva and biopsy samples) compared to a lesser proportion (12.6 percent
      and 12.6 percent, respectively) of those who consumed boiled or filtered water.
      The study also found that subjects who preferred home-cooked food (57.1 percent
      and 57.7 percent) showed a lower prevalence of H. pylori in saliva and biopsy
      samples, respectively, compared to those (80 percent and 88 percent) who
      frequently ate out. CONCLUSION: The results of the present study suggest that
      besides the oral-oral route, the transmission of H. pylori also takes place
      through the consumption of food prepared under unhygienic conditions. Consumption
      of municipal tap water also has a high impact in the transmission of H. pylori.

PMID- 16572241
TI  - Psychiatric aspects of homicide in Singapore: a five-year review (1997 - 2001).
AB  - INTRODUCTION: The association between mental illness and violent offenders is an
      important issue not just for psychiatrists but for the public as well. Several
      studies have linked an increased prevalence of psychiatric illness among
      offenders of violent crimes. This study seeks to update the psychiatric community
      in Singapore on individuals charged with murder from 1997 to 2001, all of whom
      received a psychiatric assessment. METHODS: 110 individuals were charged with
      murder from 1997 to 2001. Socio-demographical data, psychiatric diagnoses,
      offence and victim profiles and court outcomes were obtained from prison records
      and psychiatric files. RESULTS: There were 110 individuals charged with murder
      between January 1, 1997 to December 31, 2001, with a total of 113 victims. In 70
      of the cases, one offender killed one victim. Offenders were mostly unmarried
      males in the 20-39 year age group who received a secondary school level of
      education or less. 57 of the remandees were found not to suffer from any mental
      illness. Alcohol abuse and dependence disorders accounted for the largest
      diagnostic group. Depressive disorders accounted for 9.1 percent of the accused
      persons and schizophrenia, 6.4 percent. Victim profiles and court outcomes are
      also described. A comparison is drawn between this study and the last large
      report on homicides in Singapore, published in 1985. No difference is detected
      when the rates of schizophrenia and depression are compared between the two eras.
      CONCLUSION: Perpetrators of murder have been shown to have an increased incidence
      of psychiatric disorders. Reduction of the rate of homicide in the country may be
      achievable via the reduction of controllable factors found to be linked to the
      aetiology of murder. Alcohol and other illicit substance use are frequently found
      to be associated with homicide. The authorities are encouraged to enhance
      campaigns to dissuade alcohol abuse.

PMID- 16572243
TI  - Pregnancy outcomes from in-vitro fertilisation and intracytoplasmic sperm
      injection: a comparison.
AB  - INTRODUCTION: The purpose of this study was to compare the obstetrical course of
      in-vitro fertilisation pregnancies with and without intracytoplasmic sperm
      injection, and to ascertain any difference in the outcome. Both singleton and
      multiple pregnancies were assessed individually in areas where they could
      confound results. METHODS: This was a retrospective analysis of all successful in
      vitro fertilisation pregnancies at the Singapore General Hospital during the
      period 1998-2003. A total of 271 pregnancies with and without intracytoplasmic
      sperm injection were evaluated. The details of the pregnancies were obtained from
      the Assisted Reproductive Technology Registry and Birth Defects Registry.
      RESULTS: The obstetrical outcome was comparable between the two groups, in terms
      of the number of deliveries, biochemical and ectopic pregnancies. There was no
      significant difference in the miscarriage rate. The preterm rates for an
      intracytoplasmic injection pregnancy were two times higher than that reported in
      literature for both singletons and multiple pregnancies. The singleton
      intracytoplasmic sperm injection pregnancies were more likely to deliver preterm
      (17.5 percent, p-value is 0.041) compared to the ones without intracytoplasmic
      injection (5.7 percent). The average singleton birth weight was lower for the
      former (2.94 [+/-0.53] kg) than for the latter (3.19 [+/-0.48] kg, p-value is
      0.0173). No definite conclusion could be reached regarding the differences in
      congenital abnormalities between the two groups. CONCLUSION: The obstetrical
      course of an in-vitro fertilisation pregnancy with intracytoplasmic sperm
      injection pregnancy appears to be similar to one without intracytoplasmic sperm
      injection except for a slight increase in the preterm deliveries and a lower
      birth weight at delivery among the singletons.

PMID- 16572242
TI  - Ageing and circadian variation in cardiovascular events.
AB  - INTRODUCTION: Circadian variation in cardiovascular events is well recognised in
      vascular events. This study aims to observe any significant difference in
      circadian variability in geriatric patients when compared to their younger
      counterparts. METHODS: This prospective study was conducted at medical emergency
      at the Government Medical College and Hospital, Chandigarh, India. All the
      patients attending medical emergency with symptoms suggestive of coronary artery
      disease were included. The time of occurrence of first symptom and subsequent
      symptoms was noted. Electrocardiography, cardiac enzymes and echocardiography
      were performed to establish the diagnosis of acute coronary syndrome. The 24-hour
      day was divided into 12 equal parts of two hours each. For the final analysis,
      the two-hour periods were grouped into six equal periods of four hours each and
      four quarters of six hours each. RESULTS: We studied 559 patients, out of whom
      459 were 65 years old or younger, and 100 patients were older than 65 years old.
      459 patients had 498 episodes in all. 100 patients above the age of 65 years had
      104 episodes. Both the groups had peaking of acute myocardial infarction in the
      early morning hours with patients older than 65 years of age having a slightly
      early peak. However, there was considerable variability for peaking of unstable
      angina and non-Q myocardial infarction. In patients older than 65 years, early
      morning peaking of events was noted whereas in 65 years or younger, the peaking
      of events was noted in the evening hours. CONCLUSION: Circadian variability
      exists in occurrence of acute coronary events and is variable in geriatric
      patients when compared to their younger counterparts.

PMID- 16572244
TI  - Microalbuminuria prevalence study in hypertensive patients with type 2 diabetes
      mellitus in Singapore.
AB  - INTRODUCTION: Microalbuminuria is a marker of increased cardiovascular morbidity
      and mortality. It represents the earliest clinical evidence of diabetic
      nephropathy. Its early detection allows for implementation of individually
      tailored cardiovascular risk reduction management programmes. Despite this,
      information on the prevalence of microalbuminuria in hypertensive patients with
      type 2 diabetes mellitus in Singapore is limited. METHODS: The Microalbuminuria
      Prevalence Study (MAPS) assessed the prevalence of macroalbuminuria and
      microalbuminuria in consecutively-screened hypertensive adult patients with type
      2 diabetes mellitus in ten Asian countries. This paper presents the results of a
      sub-analysis of data from patients in Singapore. RESULTS: Singapore contributed
      seven percent of the overall enrolment into MAPS; a total of 499 patients were
      enrolled and 388 constituted the per-protocol population (patients with
      bacteriuria and haematuria were excluded). Overall, the prevalence of diabetic
      kidney disease was high. In our study population, 23.5 percent of patients had
      macroalbuminuria (95 percent confidence interval [CI] 21.3-25.6), and 48.5
      percent of patients had microalbuminuria (95 percent CI 45.9-51.0). Only 28.1
      percent (95 percent CI 25.8-30.4) of patients were normoalbuminuric. Associated
      factors were poor glycaemic control and poor blood pressure control. CONCLUSION:
      The high prevalence (72 percent) of microalbuminuria and macroalbuminuria found
      in hypertensive patients with type 2 diabetes mellitus in Singapore is a cause
      for concern. These findings highlight the need to screen for microalbuminuria and
      better manage hypertensive patients with type 2 diabetes mellitus, if we are to
      avoid a major increase in end-stage renal disease.

PMID- 16572245
TI  - Enlarged cervical sympathetic ganglion: an unusual parapharyngeal space tumour.
AB  - Primary parapharyngeal space tumours are rare, but they pose not only diagnostic
      but also therapeutic challenges in head and neck surgery. Imaging studies, in
      particular magnetic resonance (MR) imaging, play a central role in the diagnosis
      of parapharyngeal space (PPS) tumours. Besides schwannomas, primary lesions
      arising from the sympathetic chain within the PPS are extremely rare. We describe
      a 49-year-old man in whom the cervical sympathetic ganglion became enlarged after
      radiotherapy for nasopharyngeal carcinoma, and appeared as a parapharyngeal mass.
      This phenomenon has not been reported in the literature. We also discuss the
      features of the enlarged cervical sympathetic ganglion on MR imaging.

PMID- 16572246
TI  - Isolated massive thyroid metastasis in lung cancer.
AB  - Metastasis to the thyroid gland is rare despite its rich vascular supply. Among
      the pulmonary malignancies metastasising to the thyroid, adenocarcinomas are the
      commonest. The appearance of metastatic disease in lung carcinoma indicates a
      poor prognosis and the average survival is two months. We report a 62-year-old
      woman with squamous cell carcinoma of lung metastatic to the thyroid that
      produced massive enlargement of the gland. The appearance of the secondary
      preceded the diagnosis of the primary malignancy by a few months. Ultimately, the
      patient succumbed to her disease.

PMID- 16572247
TI  - Acute acalculous cholecystitis: a rare complication of typhoid fever.
AB  - Acute acalculous cholecystitis is a very rare complication of typhoid fever, and
      may be due to multi-drug resistant and virulent forms of Salmonella infection. It
      is particularly rare in adults. A 21-year-old woman, presenting with fever,
      vomiting, diarrhoea and abdominal pain, was found to have acute acalculous
      cholecystitis due to typhoid fever on basis of ultrasonographical findings and a
      positive Widal's test for Salmonella typhi. She was treated with antibiotics and
      made a full recovery.

PMID- 16572248
TI  - Successful pregnancy with laparoscopic oocyte retrieval and in-vitro
      fertilisation in mullerian agenesis.
AB  - A 28-year-old woman with mullerian agenesis presented with primary infertility
      and was considered for laparoscopic oocyte retrieval and in-vitro fertilisation.
      Her 27-year-old younger sister served as a gestational carrier. The patient
      underwent ovarian stimulation and 11 mature oocytes were retrieved by
      laparoscopy. After successful in-vitro fertilisation, two embryos were
      transferred to the gestational carrier. Two weeks after embryo transfer, the
      pregnancy was confirmed by serum human chorionic gonadotropin levels. Another two
      weeks later, an ongoing singleton pregnancy with foetal heartbeat was confirmed
      by transvaginal ultrasonography.

PMID- 16572249
TI  - Dengue haemorrhagic fever with unusual prolonged thrombocytopaenia.
AB  - We describe a case of dengue haemorrhagic fever with prolonged thrombocytopaenia.
      A 22-year-old Malay man with no prior illness presented with a history of fever
      and generalised macular rash of four days duration. Initial work-up suggested the
      diagnosis of dengue haemorrhagic fever based on thrombocytopaenia and positive
      dengue serology. Patient recovered from acute illness by day ten, and was
      discharged from the hospital with improving platelet count. He was then noted to
      have declining platelet count on follow-up and required another hospital
      admission on day 19 of his illness because of declining platelet count. The
      patient remained hospitalised till day 44 of his illness and managed with
      repeated platelet transfusion and supportive care till he recovered
      spontaneously.

PMID- 16572250
TI  - Hip to heel approach in the growing years.

PMID- 16572251
TI  - Common bacterial infections of the hand.
AB  - Infections of the hand are commonly encountered in general practice. Delay in
      diagnosis increases the risk of tissue loss and functional impairment.
      Staphyloccocal infections are most common, but polymicrobial infections are often
      seen in immunocompromised patients. In this pictorial essay, important and common
      conditions are illustrated to demonstrate key points and pitfalls in diagnosis
      and management.

PMID- 16572252
TI  - Jottings on the history of dentistry in Singapore.

PMID- 16572254
TI  - The Viriato Study: update of antimicrobial susceptibility data of bacterial
      pathogens from community-acquired respiratory tract infections in Portugal in
      2003 and 2004.
AB  - The Viriato Study is a nationwide, prospective, multicenter surveillance study of
      the antimicrobial susceptibility of bacterial pathogens commonly associated with
      community-acquired respiratory tract infections in Portugal. In 2003 and 2004 a
      total of 2945 isolates was recovered in the 29 laboratories that participated in
      the study. Testing was undertaken in a central laboratory. Of the 513
      Streptococcus pyogenes strains isolated from patients with acute tonsillitis all
      were susceptible to penicillin and other beta-lactams but 18.9% were resistant to
      erythromycin, clarithromycin and azithromycin. The M phenotype dominated (67%),
      conferring resistance to erythromycin (MIC90 = 16 mg/L), clarythromycin and
      azithromycin, but susceptibility to clindamycin (MIC90 = 0.094 mg/L). From
      patients with lower respiratory tract infection 1,300 strains of Streptococcus
      pneumoniae, 829 of Haemophilus influenzae, and 303 of Moraxella catarrhalis were
      studied. Among S. pneumoniae isolates 18.4% were resistant to penicillin (3.5%
      showing high-level resistance), 7.1% to cefuroxime, 0.5% to amoxicillin and
      amoxicillin/clavulanate, 18.8% to erythromycin, clarithromycin and azithromycin,
      14.9% to tetracycline, 16.5% to co-trimoxazole, and 0.4% to levofloxacin. Beta
      lactamases were produced by 10.0% of H. influenzae and 96.4% of M. catarrhalis.
      In H. influenzae resistance to clarithromycin was 5.5% and to co-trimoxazole was
      13.4%. Most strains were susceptible to amoxicillin/clavulanate, cefuroxime,
      azithromycin, tetracycline and ciprofloxacin. In M. catarrhalis resistance to co
      trimoxazole was 27.1% and to tetracycline 1.0%. All strains were susceptible to
      amoxicillin/clavulanate, cefuroxime, clarithromycin, azithromycin and
      ciprofloxacin. Penicillin was the most active antimicrobial agent against S.
      pyogenes and amoxycillin/clavulanate and the quinolones the most active in vitro
      simultaneously against S. pneumoniae, H. influenza and M. catarrhalis.

PMID- 16572255
TI  - Tracheobronchial foreign bodies in adults--experience of the Bronchology Unit of
      Centro Hospitalar de Vila Nova de Gaia.
AB  - INTRODUCTION: Foreign body aspiration (FBA) is frequent in children but uncommon
      in adults it's and often remains hidden for long periods of time. A high index of
      suspicion is essential for the correct diagnosis of this condition. Early
      extraction of FB avoids sequelae and complications. METHODS: Retrospective study
      of FBA cases in adults that occurred in a 20 year period (1985-2005). The authors
      reviewed of the clinical records of all patients admitted with the diagnosis of
      foreign body in the airway in that time period. RESULTS: In that period of time
      77 FB were extracted. Male:female ratio was 68:32%, mean age was 51.4 years and
      mean delay between FB aspiration and removal 401 days (min: 3 h, max: 21 years).
      Most common clinical presentations: acute asphyxia in 28%, persistent cough 22%.
      Nature of FB: bone fragments 33%, vegetable matter 31%. The majority of FBs (61%)
      was lodged in the right bronchial tree; 26% were radiopaque. Rigid bronchoscopy
      was performed in 75 cases and fiberoptic bronchoscopy in only two. Two patients
      needed two bronchoscopies for FB removal. There were no complications, need for
      surgery or relevant sequelae. CONCLUSIONS: FBA may happen at any age. In adults
      the clinical presentation is variable and the FBA episode is often missed,
      delaying the diagnosis. Rigid bronchoscopy proved to be an efficient and safe
      procedure. FBA must be a diagnostic hypothesis when studying an adult with long
      standing respiratory complaints.

PMID- 16572256
TI  - Effects of long term exposure to occupational noise on textile industry workers'
      lung function.
AB  - Vibroacoustic disease is a pathology caused by long occupational exposure to
      large pressure amplitude and low frequency noise. It is a systemic disease, with
      evolvement of respiratory structures. The exposure workers to this noise of
      textile industry may favour alterations in lung function. We studied 28 women
      working more than ten years in cotton-mill rooms to evaluate their lung function,
      including Spirometry, forced oscillation technique (I.O.S.) and Diffusion
      capacity. These results were compared with those of 30 women of similar ages not
      exposed to similar noise and not presenting respiratory disease. Statistical
      significance (P<0.05) was found with FEV25, R5 and Delta Rs5-Rs20. There was a
      resistance frequency dependence in 36% of the population exposed to noise, not
      statistically confirmed. Neither restriction nor changes in diffusing capacity
      where detected. CONCLUSION: The analysis of global alterations of lung function
      parameters suggests small airways aggression by noise. However we cannot
      definitively exclude the influence of cotton dust inhalation in itself which
      effects could be increased by the loss of ciliated cells and impairment of
      airways clearance caused by noise.

PMID- 16572257
TI  - [Pulmonary function testing in bone marrow transplantation: a systematic review].
AB  - The pulmonary function test plays an important role in the management of
      pulmonary complications after bone marrow transplantation. Although its utility
      in helping to predict the likelihood of developing post transplant pulmonary
      complications and mortality is not well established, current data indicate that
      pre-transplant pulmonary function tests are important as a reference for the
      interpretation of post transplant pulmonary function tests and for identifying
      patients at high risk of developing pulmonary complications and/or mortality
      after bone marrow transplantation.

PMID- 16572258
TI  - The polysialylated neural cell adhesion molecule promotes neurogenesis in vitro.
AB  - A characteristic feature of neurogenic sites in the postnatal brain is the
      expression of the polysialylated forms of the neural cell adhesion molecule (PSA
      NCAM). To investigate the role of PSA-NCAM in generation of neuronal populations,
      we developed an in vitro model where neurogenesis occurs in primary cortical
      cultures following serum withdrawal. We show that removal or inactivation of the
      PSA tail of NCAM in these cultures leads to a significant decrease in the number
      of newly generated neurons. Similarly, cultures prepared from NCAM knock-out mice
      exhibit a significantly reduced neurogenesis. Pulse-chase experiments using the
      proliferation marker BrdU reveal that the lack of PSA does not affect the mitotic
      rate of neural progenitors but rather, it reduces the early survival of newly
      generated neurons. These results suggest that, in addition to its role in the
      migration of neuronal progenitors, PSA-NCAM is required for the adequate survival
      of these cells.

PMID- 16572259
TI  - From punch to profile.
AB  - In this essay an aspect of my research is highlighted that has its roots in the
      mid seventies with the implementation of the 'Palkovits punch' procedure. This
      methodology was introduced when radiochemical and radio-immunoassay methods
      became sufficiently sensitive to measure key molecules for chemical
      neurotransmission and metabolism in minute amounts of brain tissue. For
      application of today's laser guided microdissection this knowledge of functional
      neuro-anatomy is indispensable.

PMID- 16572260
TI  - Molecular analysis of the magnocellular neuroendocrine phenotype: from the
      micropunch to laser microdissection.
AB  - Microdissection of selected regions of central nervous system (CNS) has provided
      the basis of modern chemoarchitectonics. Laser microdissection is a modern
      variant of the "Palkovits punch" technique and used together with gene array
      analysis has revolutionalized CNS molecular analysis. Here we describe the use of
      such an approach to elucidate molecules selectively expressed in magnocellular
      neuroendocrine cells (MCNs) in the supraoptic nucleus (SON). We found 123 genes
      that are preferentially expressed in the SON, and of these, 89 were substantially
      osmoregulated in their expression. One of these, C1q domain containing 1, is a
      novel gene that is osmoregulated much more than even vasopressin itself.

PMID- 16572261
TI  - The development of face processing in autism.
AB  - Both behavioral and neuroimaging evidence indicate that individuals with autism
      demonstrate marked abnormalities in the processing of faces. These abnormalities
      are often explained as either the result of an innate impairment to specialized
      neural systems or as a secondary consequence of reduced levels of social
      interest. A review of the developmental literature on typical and atypical face
      processing supports a synthesis of these two hypotheses by demonstrating that
      face processing is an emergent and developmental skill that is heavily mediated
      by early experience with faces. Individuals with autism may possess central
      nervous system irregularities that fail to attribute special status to faces,
      thereby limiting the visual input required for the development of neural regions
      specialized for face processing.

PMID- 16572263
TI  - Interactions between THC and cannabidiol in mouse models of cannabinoid activity.
AB  - RATIONALE: Interest persists in characterizing potential interactions between
      Delta(9)-tetrahydocannabinol (THC) and other marijuana constituents such as
      cannabidiol (CBD). Such interactions may have important implications for
      understanding the long-term health consequences of chronic marijuana use as well
      as for attempts to develop therapeutic uses for THC and other CB(1) agonists.
      OBJECTIVES: We investigated whether CBD may modulate the pharmacological effects
      of intravenously administered THC or inhaled marijuana smoke on hypoactivity,
      antinociception, catalepsy, and hypothermia, the well characterized models of
      cannabinoid activity. RESULTS: Intravenously administered CBD possessed very
      little activity on its own and, at a dose equal to a maximally effective dose of
      THC (3 mg/kg), failed to alter THC's effects on any measure. However, higher
      doses of CBD (ED(50)=7.4 mg/kg) dose-dependently potentiated the antinociceptive
      effects of a low dose of THC (0.3 mg/kg). Pretreatment with 30 mg/kg CBD, but not
      3 mg/kg, significantly elevated THC blood and brain levels. No interactions
      between THC and CBD were observed in several variations of a marijuana smoke
      exposure model. Either quantities of CBD were applied directly to marijuana, CBD
      and THC were both applied to placebo plant material, or mice were pretreated
      intravenously with 30 mg/kg CBD before being exposed to marijuana smoke.
      CONCLUSIONS: As the amount of CBD found in most marijuana strains in the US is
      considerably less than that of THC, these results suggest that CBD concentrations
      relevant to what is normally found in marijuana exert very little, if any,
      modulatory effects on CB(1)-receptor-mediated pharmacological effects of
      marijuana smoke.

PMID- 16572262
TI  - Development of tolerance and sensitization to different opioid agonists in rats.
AB  - RATIONALE: Despite numerous investigations, the mechanisms underlying the
      development of opioid tolerance are far from clear. However, several in vitro
      studies implicated a protective role of agonist-induced micro-opioid receptor
      endocytosis in the development of opioid tolerance. Moreover, we have recently
      demonstrated that the high-efficacy agonist etonitazene promotes rapid
      endocytosis of micro-opioid receptors, whereas the agonist morphine and the low
      efficacy agonist buprenorphine fail to promote detectable receptor endocytosis in
      micro-opioid receptor expressing HEK293 cells. OBJECTIVES: The present study
      explored the effects of these opioids on the development of tolerance and
      sensitization in rats in vivo. METHODS: The opioid effects were quantified using
      the hot plate, electric tail root stimulation, and the locomotor activity chamber
      in male Wistar rats. Dose-response curves were generated for each test drug. To
      induce tolerance, equieffective doses of etonitazene, morphine, and buprenorphine
      were administered daily for 29 days. RESULTS: We found that chronic treatment
      with the non-internalizing drugs buprenorphine and morphine resulted in a greater
      development of tolerance than etonitazene. In addition, the sensitization to the
      locomotor stimulant effect was high after buprenorphine and morphine, but was
      lacking after chronic etonitazene application. CONCLUSION: The results support a
      role for the endocytotic potency of agonists in the development of tolerance and
      addiction during long-term opioid treatment.

PMID- 16572264
TI  - Lithium and inositol: effects on brain water homeostasis in the rat.
AB  - RATIONALE: Since its earliest use in psychiatry, lithium has been known to alter
      body water homeostasis. Although lithium is also known to decrease the
      concentration of inositol, an important brain osmolyte, little is known of the
      effects of lithium on brain water homeostasis. OBJECTIVE: To determine whether
      lithium alters brain water homeostasis, and, if so, whether the mechanism
      involves changes in inositol concentration. MATERIALS AND METHODS: Rats were fed
      regular food or regular food plus lithium chloride for either 11 days or 5 weeks.
      Brains were dissected and assayed for tissue water by the wet-dry method and for
      inositol by gas chromatography-mass spectrometry. RESULTS: We found a
      statistically significant (p=0.05, corrected) 3.1% mean elevation in frontal
      cortex tissue water in 5-week lithium-fed rats (86.7+/-3.9%), compared to control
      rats (83.6+/-2.6%). Inositol concentration correlated inversely with percent
      tissue water (r=-0.50, p=0.003, corrected) in pooled samples of 5-week lithium
      fed rats, and was significantly lower in frontal cortex and hippocampus of 5-week
      lithium-fed rats, compared to controls. Rats fed lithium for 11 days did not
      differ significantly from controls on either variable. CONCLUSIONS: This is the
      first report of a lithium-induced increase in brain tissue water. Although the
      mechanism is unclear, it does not appear to result from changes in brain inositol
      concentration or blood sodium concentration. This finding may have implications
      for the therapeutic or toxic effects of lithium on brain, because increased
      tissue water can augment cell excitability.

PMID- 16572265
TI  - 5HT(3) antagonism abolishes the emotion potentiated startle effect in humans.
AB  - RATIONALE: The serotonergic system has been implicated in emotional processing in
      animals and humans. Although the contribution of different receptor subtypes has
      been hypothesised, there have been few direct tests of this in human subjects.
      OBJECTIVES: The current study aimed to explore the involvement of the serotonin
      type 3 (5HT3) receptor subtype in a battery of emotional processing tasks
      previously found to be sensitive to SSRI administration. MATERIALS AND METHODS:
      Healthy volunteers were randomised to receive the 5HT3 antagonist, ondansetron
      (12 mg, oral), or placebo in a double blind between groups design. Emotional
      processing was assessed using three tasks: affective modulation of the startle
      reflex, emotional categorisation and memory and facial expression recognition.
      Subjective state ratings, blood pressure and pulse were also collected before and
      after ondansetron and placebo. RESULTS: Ondansetron was well tolerated and did
      not affect subjective measures of mood, anxiety or well-being in these healthy
      volunteers. However, the emotion potentiated effect was abolished in the
      volunteers receiving ondansetron. Facial expression recognition and emotional
      memory were not significantly affected. CONCLUSIONS: These results suggest an
      involvement of 5HT3 receptors in certain aspects of fear processing in humans.
      These effects are consistent with anxiolytic actions of 5HT3 antagonism in animal
      models and suggest that the 5HT3 receptor may play a role in the effects of
      serotonergic manipulations on fear and anxiety.

PMID- 16572266
TI  - A statistical approach for classifying change in cognitive function in
      individuals following pharmacologic challenge: an example with alprazolam.
AB  - INTRODUCTION: The effects of any drug treatment on cognitive function are
      typically studied in groups of subjects. Observations made about the behavior of
      the drug, in the study sample, are then generalized to the population from which
      the sample was drawn. However, the magnitude and pharmacodynamic qualities of the
      response to many central nervous system-active drugs are known to vary in the
      population. Therefore, it is useful to consider statistical models for the
      detection of cognitive change in response to a drug treatment in individual
      subjects. MATERIALS AND METHODS: In this report, we first outline the statistical
      assumptions and requirements for the reliable estimation of clinically relevant
      individual change in cognition. We then used the sedative benzodiazepine,
      alprazolam, as a pharmacologic challenge in healthy volunteer subjects to test
      our statistical model, using a parallel groups placebo-controlled study design.
      After treatment, the nature and severity of alprazolam-induced cognitive change
      was determined for each individual. RESULTS: Our proposed method and analysis
      showed an excellent sensitivity and specificity for alprazolam-related cognitive
      deterioration in individuals. DISCUSSION AND CONCLUSIONS: These findings,
      although preliminary, suggest that statistically reliable decisions about the
      effects of sedative drugs on cognition can be made for individuals.

PMID- 16572267
TI  - Genetic variation at the growth hormone (GH1) and growth hormone receptor (GHR)
      loci as a risk factor for hypertension and stroke.
AB  - An increased prevalence of both hypertension and cerebrovascular stroke is
      apparent in growth hormone (GH) deficiency whilst hypertension is a frequent
      complication in acromegaly. This has suggested a possible link between GH,
      stature and arterial function. Since the risk of both hypertension and stroke
      also appears to be inversely correlated with adult height, we have instigated an
      exploratory study to assess whether inter-individual variation in the genes
      encoding human growth hormone (GH1) and the GH receptor (GHR) might be associated
      with an increased risk of hypertension and stroke. GH1 promoter haplotypes were
      found to differ significantly not only between hypertensive patients (n = 111)
      and controls (n = 121) but also between stroke patients (n = 155) and controls (n
      = 158). Intriguingly, the association between GH1 promoter haplotype and risk of
      hypertension was much greater in females than in males. An inverse correlation
      between height and central systolic blood pressure was apparent in both
      hypertensive patients and normal controls but was much stronger in individuals
      carrying at least one GH1 promoter risk haplotype. The GH1 genotype therefore
      constitutes a risk factor for hypertension that interacts with stature. A strong
      association was found between the presence of at least one GH1 risk haplotype and
      a family history of stroke at an early age (odds ratio: 9.07, 95% confidence
      interval: 1.14-72.22). Three novel GH variants (Arg16His, Phe176Cys, Cys189Arg)
      were identified during the course of this study. Although two exhibited markedly
      reduced biological activity in vitro, their clinical significance remains
      unclear. No association was found between GHR genotype and either hypertension or
      stroke, nor was any interaction noted between GHR and GH1 genotypes in terms of a
      disease association. However, an association between GHRd3 genotype and
      hypertension was observed among stroke patients, particularly females. Elevated
      HDL was found to be a risk factor for hypertension in individuals lacking a copy
      of the GHRd3 allele. Weak associations with GHR genotype were also noted for
      peripheral systolic and diastolic blood pressure in hypertensive patients.
      Although the underlying mechanisms are still unclear, our findings are consistent
      with a complex relationship between height, hypertension, GH1 promoter haplotype,
      GHR polymorphism and the risk of stroke.

PMID- 16572268
TI  - Common chromatin structures at breakpoint cluster regions may lead to chromosomal
      translocations found in chronic and acute leukemias.
AB  - The t(9;22) BCR/ABL fusion is associated with over 90% of chronic myelogenous and
      25% of acute lymphocytic leukemia. Chromosome 11q23 translocations in acute
      myeloid and lymphoid leukemia cells demonstrate myeloid lymphoid leukemia (MLL)
      fusions with over 40 gene partners, like AF9 and AF4 on chromosomes 9 and 4,
      respectively. Therapy-related leukemia is associated with the above gene
      rearrangements following the treatment with topoisomerase II (topo II)
      inhibitors. BCR, ABL, MLL, AF9 and AF4 have defined patient breakpoint cluster
      regions. Chromatin structural elements including topo II and DNase I cleavage
      sites and scaffold attachment sites have previously been shown to closely
      associate with the MLL and AF9 breakpoint cluster regions, implicating these
      elements in non-homologous recombination (NHR). In this report, using cell lines
      and primary cells, chromatin structural elements were analyzed in BCR, ABL and
      AF4 and, for comparison, in MLL2, which is a homolog to MLL, but not associated
      with chromosome translocations. Topo II and DNase I cleavage sites associated
      with all breakpoint cluster regions, whereas SARs associated with ABL and AF4,
      but not with BCR. No close breakpoint clustering with the topo II/DNase I sites
      were observed; however, a statistically significant 5' or 3' distribution of
      patient breakpoints to the topo II DNase I sites was found, implicating DNA
      repair and exonucleases. Although MLL2 was expressed in all cell lines tested,
      except for the presence of one DNAse I site in the promoter, no other structural
      elements were found in MLL2. A NHR model presented demonstrates the importance of
      chromatin structure in chromosome translocations involved with leukemia.

PMID- 16572269
TI  - Highly compact folding of chromatin induced by cellular cation concentrations.
      Evidence from atomic force microscopy studies in aqueous solution.
AB  - We have performed a very extensive investigation of chromatin folding in
      different buffers over a wide range of ionic conditions similar to those found in
      eukaryotic cells. Our results show that in the presence of physiological
      concentrations of monovalent cations and/or low concentrations of divalent
      cations, small chicken erythrocyte chromatin fragments and chromatin from HeLa
      cells observed by transmission electron microscopy (TEM) show a compact folding,
      forming circular bodies of approximately 35 nm in diameter that were found
      previously in our laboratory in studies performed under very limited conditions.
      Since TEM images are obtained with dehydrated samples, we have performed atomic
      force microscopy (AFM) experiments to analyze chromatin structure in the presence
      of solutions containing different cation concentrations. The highly compact
      circular structures (in which individual nucleosomes are not visible as separated
      units) produced by small chromatin fragments in interphase ionic conditions
      observed by AFM are equivalent to the structures observed by TEM with chromatin
      samples prepared under the same ionic conditions. We have also carried out
      experiments of sedimentation and trypsin digestion of chromatin fragments; the
      results obtained confirm our AFM observations. Our results suggest that the
      compaction of bulk interphase chromatin in solution at room temperature is
      considerably higher than that generally considered in current literature. The
      dense chromatin folding observed in this study is consistent with the requirement
      of compact chromatin structures as starting elements for the building of
      metaphase chromosomes, but poses a difficult physical problem for gene expression
      during interphase.

PMID- 16572270
TI  - Temporins, anti-infective peptides with expanding properties.
AB  - Antimicrobial peptides are effector molecules of the innate immune response of
      all pluricellular organisms, providing them with first-line defence against
      pathogens. Amphibian skin secretions represent one of the richest natural sources
      for such peptide antibiotics, and temporins, a large family of antimicrobial
      peptides from frog skin, are among the smallest ones found in nature to date.
      Their functional role and modes of action have been described, along with their
      interesting and unique properties. These properties make temporins good molecules
      for an in-depth understanding of host defence peptides in general. Furthermore,
      they are attractive templates for the future design of new therapeutics against
      infectious diseases with new modes of action, urgently needed due to the
      increasing resistance of microorganisms to the available drugs.

PMID- 16572271
TI  - Relationship between parental psychopathology, parenting strategies and child
      mental health--findings from the GB national study.
AB  - BACKGROUND: Parental and child psychiatric disorders have been found to be
      associated, and this association can be mediated by other psychosocial variables,
      including parenting attitudes and strategies. As most previous studies included
      clinical samples, the purpose of this study was to establish the relationship
      between parental psychopathology and parenting strategies with child psychiatric
      disorders in a national survey population. METHODS: The sample included 10,438
      children of 5-15 years and their parents, from representative UK households.
      Families were assessed on child psychiatric diagnosis, parental psychopathology,
      family functioning, and socioeconomic status. Parenting strategies included using
      rewards, physical and non-physical punishments towards their child. FINDINGS:
      Parental psychopathology scores (OR 3.99, 95% CI 3.13-5.09) and non-physical
      punishment (OR 1.50, 95% CI 1.27-1.76) were associated with child psychiatric
      disorders. This association was particularly prominent among children with
      conduct disorders: parental psychopathology scores (OR 3.13, 95% CI 2.28-4.30)
      and non-physical punishment (OR 3.19, 95% CI 2.55-3.97). Absence of child
      psychopathology was associated with a combination of rewarding and non-punitive
      parenting strategies. CONCLUSIONS: Although parents in the general population may
      be using less physical strategies than in the past, non-physical punishment is
      strongly related to mental health problems in children. Enhancement of positive
      parenting through universal and targeted interventions is an important preventive
      strategy.

PMID- 16572273
TI  - Perceived work stress, imbalance between work and family/personal lives, and
      mental disorders.
AB  - BACKGROUND: Occupational mental health research has been focusing on the
      relationship between work stress and depression. However, the impacts of work
      stress on anxiety disorders and of imbalance between work and family life on
      workers' mental health have not been well studied. This analysis investigated the
      association between levels of perceived work stress and of imbalance between work
      and family/personal lives and current mood/anxiety disorders. METHOD: This was a
      cross-sectional study using data from the Canadian Community Health Survey-Mental
      Health and Well-being (CCHS-1.2) (n=36,984). Mood and anxiety disorders were
      measured using the World Mental Health-Composite International Diagnostic
      Interview. RESULTS: The 1-month prevalence of mood and anxiety disorders among
      those with a work stress score at the 75th percentile value and above was 3.6%
      and 4.0%. Among those who reported that their work and family/personal lives
      "never" balanced in the past month, the 1-month prevalence of mood and anxiety
      disorders was 21.2% and 17.9%. In multivariate analyses, work stress and
      imbalance between work and family/personal lives were independently associated
      with mood and anxiety disorders. There was no evidence that perceived work stress
      interacted with imbalance between work and family/personal lives to increase the
      likelihood of having mental disorders. Gender was associated with anxiety
      disorders, but not with major depressive disorder and mood disorders.
      CONCLUSIONS: Work stress and imbalance between work and family/personal lives may
      be part of the etiology of mood and anxiety disorders in the working population.
      Community based longitudinal studies are needed to delineate the causal
      relationships among work stress, imbalance between work and family/personal lives
      and mental disorders.

PMID- 16572272
TI  - Childhood victimisation and developmental expression of non-clinical delusional
      ideation and hallucinatory experiences: victimisation and non-clinical psychotic
      experiences.
AB  - BACKGROUND: Victimisation in childhood may be associated with adult psychosis.
      The current study examined this association in the crucial developmental period
      of early adolescence and investigated whether (1) unwanted sexual experiences,
      and (2) being bullied, were associated with non-clinical delusional ideation and
      hallucinatory experiences in a general population sample of 14 year olds.
      METHODS: Data were derived from standard health screenings of the Youth Health
      Care Divisions of the Municipal Health Services in Maastricht, the Netherlands. A
      self-report questionnaire was filled out by a total of 1290 adolescents to assess
      non-clinical psychotic experiences, as well as experiences of being bullied and
      sexual trauma. RESULTS: Non-clinical psychotic experiences were strongly and
      independently associated with both bullying (OR=2.9, 95% CI 1.8-4.8) and sexual
      trauma (OR=4.8, 95% CI 2.3-10.1). CONCLUSIONS: The results suggest that reported
      associations between childhood victimisation and adult psychosis can be
      understood in a developmental framework of onset of at-risk mental states in
      early adolescence. In addition, the data suggest that the traumatic experience of
      being bullied may also feed the cognitive and biological mechanisms underlying
      formation of psychotic ideation.

PMID- 16572274
TI  - Norms for mental health services in South Africa.
AB  - BACKGROUND: In the aftermath of apartheid, South Africa has inherited a
      fragmented, under-resourced and inequitable public sector mental health service.
      Attempts are being made to reform mental health services, in keeping with new
      health policy, which proposes the downscaling of psychiatric institutions and the
      development of community-based services. This study set out to develop a set of
      service norms for the care of people with severe psychiatric conditions (SPC) in
      South Africa, to assist the implementation of the new policy. METHODS: A national
      situation analysis of current public sector mental health services was conducted.
      A model was developed for estimating the mental health service resource needs of
      people with SPC. Following consultation with provincial stakeholders, a set of
      service norms were developed taking into account national indicators from the
      situation analysis (as a baseline level) and proposals of the model (as a target
      level). RESULTS: The study recommends an increase in the number of acute
      psychiatric beds in general hospitals; development of community-based residential
      care; redistribution of staff from hospital to community services, particularly
      in rural areas; and the development of information systems to monitor the
      transitions to community-based care. CONCLUSIONS: The norms proposals presented
      in this study express mental health service needs in terms of quantifiable
      service resource and utilisation levels. In doing so, the study attempts to make
      explicit the assumptions and values on which planning is based.

PMID- 16572276
TI  - Screening and early psychological intervention for depression in schools :
      systematic review and meta-analysis.
AB  - Depression in children and adolescents is considerably undertreated, and the
      school may be a good setting for identifying and treating depression. We
      conducted a meta-analysis of studies in which students were screened for
      depression, and those with depressive symptoms were treated with a psychological
      intervention. Only randomised controlled trials were included. Eight studies met
      the inclusion criteria. Five studies focused on younger children (7-14 years) and
      three studies were aimed at adolescents (12-19 years). In total 5803 students
      were screened, of whom 7.2% were included in the intervention studies (95% CI:
      7.1-7.3). The 'numbers-needed-to-screen' was 31 (95% CI: 27-32), which means that
      31 students had to be screened in order to generate one successfully treated case
      of depression. The effects of the psychological treatments at post-test were
      compared to control conditions in the 8 studies comprising 12 contrast groups,
      with a total of 413 students. The mean effect size was 0.55 (95% CI: 0.35-0.76).
      There were not enough studies to examine whether specific psychotherapies were
      superior to other psychotherapies. Although the number of studies is small and
      their quality is limited, screening and early intervention at schools may be an
      effective strategy to reduce the burden of disease from depression in children
      and adolescents. More research on the (negative) effects of these interventions
      is needed.

PMID- 16572277
TI  - New microsurgical technique for intraparenchymal lesions of the brain:
      transcylinder approach.
AB  - BACKGROUND: Although various minimally invasive approaches, including endoscopic,
      stereotaxic, and ultrasound-guided surgery, have been introduced to minimize
      damage to healthy brain tissue, the microsurgical technique has retained a
      significant role in contemporary neurosurgery. A new microsurgical approach to
      intraparenchymal brain lesions, namely, the transcylinder approach, was developed
      to realize both minimal surgical access and sufficient microsurgical technique.
      METHOD: A 0.1-mm transparent polyester film was used to create a cylindrical
      surgical route. The film was rolled into a thin stick and used to penetrate the
      brain, and a computer-aided navigation system was used from inside the stick to
      access the lesion accurately. After the stick gained access to the lesion, it was
      dilated to 2 cm, and this diameter was maintained during surgery. FINDINGS: The
      transcylinder approach was used in 11 cases, including intraparenchymal tumours
      and haematomas, and the usual microsurgical procedure was performed without
      difficulty. The film avoided unnecessary enlargement of the surgical field and
      minimized injury to the brain. Intra-operative ultrasonography also can be used
      to identify the lesion through the cylinder because the polyester film does not
      reflect the ultrasound beam. The surgical route was observed to recover to almost
      the same size as the initial cortical incision after removal of the cylinder.
      CONCLUSIONS: The transcylinder approach could be advantageous for removing
      tumours or haematomas in the intraventricular or intraparenchymal regions. By
      avoiding unnecessary retraction, it significantly reduces the risk of injury to
      surrounding brain tissue while facilitating precise microsurgical technique. The
      accuracy of this minimally invasive technique can be enhanced when used in
      conjunction with frameless stereotaxy and intra-operative ultrasound guidance.

PMID- 16572275
TI  - Negative life events, social support and gender difference in depression: a
      multinational community survey with data from the ODIN study.
AB  - OBJECTIVE: To explore if differences in negative life events, vulnerability and
      social support may explain the gender difference in depression. METHODS: Cross
      sectional, multinational, community survey from five European countries (n =
      8,787). Depression is measured by Beck Depression Inventory, whereas negative
      life events and social support are measured by various questionnaires. RESULTS:
      Women report slightly more negative life events than men do, mainly related to
      the social network, but more social support in general and in connection with
      reported life events. This trend is the same in all participating countries
      except Spain, where there is no gender difference in the reported support. In
      general, women are not more vulnerable to negative life events than men are.
      However, women with no social support, who are exposed to life events, are more
      vulnerable than men without support. CONCLUSION: The higher rate of depression in
      women is not explained by gender differences in negative life events, social
      support or vulnerability.

PMID- 16572278
TI  - Spinal metastasis from cranial meningeal hemangiopericytomas.
AB  - Spine metastasis from cranial meningeal hemangiopericytomas are extremely rare,
      with five surgically verified cases. We describe a case of a 55-year-old female
      diagnosed with metastatic hemangiopericytoma to the cervical spine 78 months
      after the first operation. Because of the long latency period, aggressive spinal
      surveillance should be advocated along with repeated bone scintigraphy and MRI.

PMID- 16572279
TI  - Cavernous malformation of the internal auditory canal.
AB  - Cavernous malformations of the internal auditory canal are a rare clinical entity
      that, however, should be considered in the differential diagnosis of
      intracanalicular masses. Even though this type of malformation is usually
      associated with an evident gadolinium enhancement at MR examination, in some
      patients, like in this case, the signal characteristics may be not sufficiently
      specific to allow the correct preoperative diagnosis. Nevertheless, the clinical
      history, in particular, a rapid onset of cranial nerve deficits, lead to the
      suspicion of a vascular malformation.

PMID- 16572280
TI  - Prevalence of anal incontinence according to age and gender: a systematic review
      and meta-regression analysis.
AB  - CONTEXT: Anal incontinence is increasingly being recognised as a significant
      cause of physical and psychological morbidity with implications for healthcare
      provision within the community. There is controversy about which population
      groups are most disadvantaged by this chronic condition. OBJECTIVES: The aim of
      this study was to evaluate the prevalence of this condition in the community
      according to age and gender, a systematic review was performed. DATA SOURCES:
      Data were from Embase, Medline, bibliographies of known articles and contact with
      experts. STUDY SELECTION: Studies were selected if data on anal incontinence
      could be extracted for participants over 15 years of age and living in the
      community. DATA EXTRACTION: Data were extracted using a piloted form on
      participants' characteristics, study quality and incontinence rates. DATA
      SYNTHESIS: Meta-analysis was used to combine data from multiple studies, and meta
      regression evaluated the variation in rates according to age and gender in an
      analysis adjusted for study quality. RESULTS: There were 29 studies (69,152
      participants), of which 5 met over half of the high quality criteria. The rate of
      solid and liquid faecal incontinence among people aged 15-60 years was 0.8% [95%
      confidence interval (CI) 0.3-1.9] in men and 1.6% (95% CI 0.8-3.1) in women. In
      those aged over 60, this increased to 5.1% (95% CI 3.4-7.6) in men and 6.2% (95%
      CI 4.9-8.0) in women. Meta-regression showed that age had a significant influence
      on rates of solid and liquid faecal incontinence (p = 0.007), but not gender (p =
      0.368) or study quality (p = 0.085). CONCLUSIONS: The rate of solid and liquid
      faecal incontinence in older people is significantly higher than their younger
      counterparts. Gender differences in rates did not reach statistical significance.

PMID- 16572282
TI  - Anti-neutrophil cytoplasmic antibodies in leprosy.
AB  - INTRODUCTION: Anti-Neutrophil Cytoplasmic Antibodies (ANCA) are auto-antibodies
      directed to intracellular components of neutrophils and used to be considered as
      present almost exclusively in granulomatous vasculitis. Recently, these auto
      antibodies have been found in other autoimmune disorders as well as infectious
      diseases. MATERIALS AND METHODS: We studied patients with leprosy confirmed by
      bacilloscopy and/or skin biopsy, in reaction phase from the Ambulatorio de
      Hanseniase do Hospital Universitario Professor Edgar Santos. ANCA and Antinuclear
      antibodies (ANA) were determined by indirect immunofluorescence using
      commercially available kits. RESULTS: Twenty patients were enrolled in our study,
      nine males and 11 females. The mean age was 36.9+/-18.2 years. ANCA were present
      only in one patient, with a perinuclear staining pattern (p-ANCA), and no patient
      tested positive for ANA. DISCUSSION: Although other studies have shown the
      presence of ANCA in leprosy, the low frequency of these antibodies in leprosy
      sera demonstrated in the present study illustrates the high specificity of ANCA
      for the diagnosis of Wegener granulomatosis.

PMID- 16572281
TI  - Pulmonary involvement in ankylosing spondylitis.
AB  - This is a prospective study analyzing 52 asymptomatic, consecutive patients with
      ankylosing spondylitis (AS), who submitted to a pulmonary investigation that
      included plain chest radiography, pulmonary function test (PFT), and thoracic
      high-resolution computed tomography (HRCT). The results were compared according
      to sex, race, dorsal spine involvement, thoracic diameter, smoking status, and
      HLA-B27. There were four patients (8%) with an altered plain chest radiograph.
      PFT presented a restrictive pattern in 52% of the patients. Thoracic HRCT showed
      abnormalities in 21 patients (40%), predominantly nonspecific linear parenchymal
      opacities (19%), lymphadenopathy (12%), emphysema (10%), bronchiectasis (8%), and
      pleural involvement (8%). Linear parenchymal opacities were associated with a
      smoking history (p=0.026) and dorsal spine involvement (p=0.032). HLA-B27 was not
      associated with any abnormality. A lower thoracic diameter was observed in
      patients with dorsal spine involvement (p=0.0001), restrictive pattern at PFT
      (p=0.023), and linear parenchymal opacities (p=0.015). The study concluded that
      nonspecific subclinical pulmonary involvement is frequent in AS.

PMID- 16572283
TI  - Autoantibodies in rheumatoid arthritis: association with severity of disease in
      established RA.
AB  - INTRODUCTION: Autoantibodies in rheumatoid arthritis (RA) are useful both for
      diagnosis and prognosis. Antibodies directed against citrullinated antigens have
      recently been shown to predict development of RA as well as poor outcome in early
      arthritis. Data on their role in established RA is limited. We studied the
      association of various autoantibodies in RA with its severity. MATERIALS AND
      METHODS: A total of one hundred and twenty nine-patients with established RA was
      enrolled and sera were collected and stored at -70 degrees C. Data regarding
      erosions, deformities, and extra-articular features were collected. IgM
      rheumatoid factor (RF) was measured using nephelometry and value above 20 U was
      considered positive. IgA RF was measured by enzyme-linked immunosorbent assay
      (ELISA) and value above the mean+/-2 SD of normal healthy control was taken as
      positive. Anti-keratin antibody (AKA) was detected by indirect immunofluorescence
      assay using rat esophagus as substrate. Anti-cyclic citrullinated peptide (CCP)
      antibodies were measured by commercial ELISA and a value above 5 U was considered
      as positive. RESULTS: The prevalence of various autoantibodies was: IgM RF 82.2%,
      anti-CCP antibodies 82.2%, AKA 51.9%, and anti IgA RF 45%. The concordance rate
      of anti-CCP antibodies with IgM RF was 83%, with AKA 68%, and with IgA RF 60.5%.
      All but one patient positive for AKA were positive for anti-CCP antibodies. The
      presence of IgM RF, AKA, and anti-CCP antibody was associated with joint erosions
      and deformities. None of the antibodies had any association with presence of
      extra-articular features. No association of IgA RF was seen with erosions,
      deformities, or extra-articular features. Among 23 seronegative RA patients, 11
      were positive for anti-CCP antibodies and 6 were AKA positive. The presence of
      anti-CCP antibodies was associated with presence of deformities (p<0.05).
      CONCLUSION: Anti-CCP antibodies are present in majority of patients with
      established RA including seronegative patients. Both anti-CCP and AKA, in
      addition to conventional marker like IgM RF, are associated with severe erosive
      disease.

PMID- 16572285
TI  - Rheumatic-like syndrome as a symptom of underlying gastric cancer.
AB  - Several observations imply that atypical rheumatic manifestations may be
      associated with occult neoplasia. A 71-year-old woman was admitted to the
      hospital three times in 2 years. Initially, she was admitted for investigation of
      an iron-deficient anemia associated with upper intestinal tract symptoms.
      Endoscopy revealed hiatus hernia, esophagitis, and duodenal ulcer with a
      Helicobacter pylori infection, but there were no signs of malignancy, and the
      patient received appropriate drug treatment. Two years later, she presented with
      arthralgias concerning the upper and lower limbs in an asymmetrical distribution,
      low fever, and persistence of the anemia, despite the treatment she had received
      and the fact that her gastrointestinal symptoms had long ceased. Immunological
      assays showed no specific rheumatic disorder, and the patient was discharged
      after showing significant improvement with the use of COX-2 selective NSAIDs.
      Finally, 4 months later, she was readmitted with worsening of the arthralgias,
      arthritis in the right radiocarpal joint, and severe anemia. Hematemesis that
      occurred during her hospital stay led to an emergency endoscopy and the diagnosis
      of gastric adenocarcinoma. Only a few cases have been reported so far concerning
      rheumatic manifestations as signs of an occult gastric cancer. Thus, there must
      be some degree of suspicion when dealing with patients with anemia and rheumatic
      symptoms that cannot be classified into a particular rheumatologic entity,
      because they might conceal a gastrointestinal malignancy not yet evident.

PMID- 16572284
TI  - Durable remission of HIV-negative, Kaposi's sarcoma herpes virus-associated
      multicentric Castleman disease in patient with rheumatoid arthritis treated with
      methotrexate.
AB  - Multicentric Castleman disease (MCD) is a nonneoplastic lymphoproliferative
      disorder that has a poor prognosis. Optimal treatment is unknown. There are a few
      reported cases of MCD and rheumatoid arthritis. In this study, we report a
      patient with rheumatoid arthritis diagnosed with Kaposi's sarcoma herpesvirus
      (KSHV, human herpesvirus-8) associated MCD that showed expression of viral IL-6.
      Treatment with methotrexate (MTX) resulted in a complete remission of her disease
      lasting for 54+ months. Multiple studies have suggested that MCD and rheumatoid
      arthritis are associated with overexpression of the growth-promoting cytokine
      interleukin-6 (IL-6), and that MTX downregulates the production of this cytokine
      in vivo. As such, we suggest that the dramatic improvement in this patient's
      disease is due to the immunomodulatory properties of MTX.

PMID- 16572286
TI  - Ascending aortic aneurysm in a man with scleroderma.
AB  - Macrovascular involvement in scleroderma has received relatively little
      attention. We hereby describe a 5.6-cm ascending aortic aneurysm in a 56-year-old
      man presenting with increased dyspnea, diagnosed with antibody-negative, rapidly
      progressive diffuse cutaneous scleroderma. The patient had sclerosis and
      induration of all extremities, face, thorax and abdomen. Other features included
      Raynaud's phenomenon, arthralgia, dysphagia, dyspnea attributed to pulmonary
      fibrosis, pericardial effusion, and cardiomyopathy. To the best of our knowledge,
      there is only one other report to date in the English language of a thoracic
      aortic aneurysm associated with scleroderma.

PMID- 16572287
TI  - Subcutaneous infection with Pseudallescheria boydii in an immunocompromised
      patient.
AB  - With the broad employment of immunosuppressive therapy, the incidence of
      Pseudallescheria boydii infections is rising. We report a first case of the
      localized subcutaneous P. boydii infection in a patient with microscopic
      polyangiitis. Favorable outcome related to the treatment with voriconazole adds
      to the growing body of evidence supporting the use of this particular agent in P.
      boydii infections.

PMID- 16572288
TI  - Correlates of knee pain in younger subjects.
AB  - The aim of this study was to describe clinical, structural and biochemical
      factors associated with knee pain in younger subjects. A cross-sectional
      convenience sample of 371 male and female subjects (mean age, 45 years, range 26
      61) was studied. Knee pain was assessed by questionnaire. Chondral defects,
      cartilage volume, and bone area of the right knee were determined using T1
      weighted fat saturation magnetic resonance imaging (MRI). X-ray was performed on
      the same knee for the assessment of radiographic features of osteoarthritis. The
      urinary C-terminal cross-linking telopeptide of type II collagen (CTX-II) was
      measured by enzyme-linked immunosorbent assay (ELISA). Height and weight were
      measured by standard protocols and body mass index (BMI) was calculated. The
      prevalence of knee pain was 35% in this sample. Chondral defect scores
      (particularly femoral and patellar but not tibial) were significantly associated
      with knee pain in a dose-response fashion (all p<0.01). Cartilage volume and bone
      area were not associated with knee pain in multivariate analysis in this sample.
      Urinary CTX-II was higher in subjects with knee pain (p=0.04), but this became
      nonsignificant after adjustment for BMI and osteophytes (both of which were
      significant) suggesting potential mechanisms of effect. In conclusion, knee pain
      is significantly associated with non-full thickness chondral defects
      (particularly femoral and patellar), osteophytes, CTX-II, and obesity but not
      other factors. MRI and biochemical measures can add to radiographs in defining
      unexplained knee pain in younger subjects.

PMID- 16572290
TI  - Preoperative and intraoperative determinants of incisional bulge following
      retroperitoneal aortic repair.
AB  - Although the left flank retroperitoneal incision is a useful approach for many
      patients undergoing major aortic reconstruction for aneurysmal and occlusive
      disease, it has been associated with weakening of the flank muscles, resulting in
      bulges varying from slight asymmetry to huge hernias. The purpose of this study
      was to determine if the incidence of this complication correlated with
      identifiable preoperative or intraoperative factors. Fifty consecutive patients
      undergoing aortic reconstruction via the retroperitoneal approach were followed
      for 1 year postoperatively for evidence of disfiguring bulges. Bulges were scored
      as follows: normal/mild, <1-inch protrusion; moderate, protrusion 1-2 inches;
      severe, protrusion >2 inches and/or pain or true herniation. Preoperatively,
      patients were administered a questionnaire to elicit demographic and comorbidity
      data. Fifty-six percent of patients developed a bulge at 1 year. In 43% of these,
      the bulge was deemed mild and in 54% moderate. One patient developed a severe
      bulge. Among preoperative comorbidities, no statistically significant
      correlations were found on bivariate analysis. However, likelihood ratios for
      bulge development of 5.5 for renal disease and 3.1 for cancer were demonstrated.
      Conversely, peripheral vascular disease had a likelihood ratio of 0.21 for bulge
      formation and emphysema, 0.28. On logistic analysis, incision >15 cm and body
      mass index (BMI) >23 mg/kg(2) were found to correlate strongly with bulge
      formation (p=0.003, odds ratio=9.1, and p=0.018, odds ratio=16.9, respectively).
      Together, these yielded a pseudo r (2) of 0.32. BMI >23 mg/kg(2 )was found to
      yield the greatest explanatory power. These same two variables were found to
      correlate with severity of bulge: p=0.02 for incision>5 cm and p=0.006 for BMI
      >23. Of note, gender, age, and extension of the incision into the interspace were
      not significant on logistic analysis. Preoperatively, surgeons should warn obese
      patients and those requiring large incisions for extensive disease of their
      increased risk for poor healing. Intraoperatively, surgeons should aim to
      minimize incision length.

PMID- 16572289
TI  - Bcl-x(L) expression in vivo in rheumatoid synovium.
AB  - To examine the expression of the apoptosis regulatory protein, Bcl-x(L), in the
      synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).
      Immunohistochemistry for Bcl-x(L) was carried out on synovial samples from
      patients with RA and OA. Reverse transcriptase polymerase chain reaction (RT-PCR)
      and Western blot analysis were performed to qualitatively examine the expression
      of Bcl-x(L). Bcl-x(L) expression was detected in the lining, endothelium and
      inflammatory cells of both RA (n=20) and OA (n=10) samples. However, there was
      significantly more expression in the lining of RA synovium compared to OA (77 vs
      61%, p<0.05). Many of the positive cells in the RA subsynovium were noted to be
      plasma cells. There was a significant correlation between Bcl-x(L) expression and
      the number of inflammatory cells in the subsynovium of RA and OA patients (r
      (s)=0.376, p<0.05, n=30). Age and disease duration did not correlate with Bcl
      x(L) expression in rheumatoid patients. Bcl-x(L) may play a role in the extended
      survival of synoviocytes and inflammatory cells in rheumatoid synovium.

PMID- 16572291
TI  - Localized administration of doxycycline suppresses aortic dilatation in an
      experimental mouse model of abdominal aortic aneurysm.
AB  - Treatment with doxycycline suppresses the development of abdominal aortic
      aneurysms (AAAs) in experimental animal models, but its use in humans can be
      accompanied by dose-related side effects. We sought to determine if localized
      administration of doxycycline can achieve inhibition of AAAs equivalent to that
      achieved by systemic treatment. C57BL/6 mice underwent transient elastase
      perfusion of the abdominal aorta to induce the development of AAAs. After 14
      days, the mean increase in aortic diameter was reduced from 167.2+/-7.8% in
      untreated mice to only 129.7+/-13.8% in mice treated with 100 mg/kg/day oral
      doxycycline (p<0.05). Using osmotic minipumps to provide continuous periaortic
      infusion of doxycycline, localized infusion at rates of 0.75 to 1.0 mg/kg/day
      suppressed AAAs to an equivalent or even greater extent than systemic treatment
      [mean increase in aortic diameter 131.5+/-14.4% at 0.75 mg/kg/day, p<0.05;
      103.2+/-13.5% at 1.0 mg/kg/day, p<0.01). Mean plasma doxycycline levels reached
      332+/- 62 ng/mL during oral administration, but the drug was undetectable in the
      circulation during localized infusion. The doxycycline concentration in aortic
      tissue extracts was 22+/- 6 ng/mL during systemic treatment compared to only
      5.6+/- 2.2 ng/mL [at 0.75 mg/kg/day] and 7.8+/- 4.0 ng/mL [at 1.0 mg/kg/day]
      during localized infusion (p<0.05). Localized administration of doxycycline can
      effectively suppress experimental AAAs with undetectable plasma drug levels, even
      at doses 100-fold lower than those used during oral drug administration.
      Localized delivery of doxycycline holds promise as a novel strategy to inhibit
      the progressive expansion of aortic aneurysms, perhaps as a pharmacological
      adjunct to endovascular (stent graft) treatment.

PMID- 16572293
TI  - Dust storms are an indication of an unhealthy environment in East Asia.
AB  - Dust storms frequently occur in Mongolia and in northern China. Each year there
      are 30 to 120 dusty days in source regions of Mongolia and 14-20 dusty days on
      the Korean Peninsula. Intense sand storms and associated dust falls produce
      environmental impacts in East Asia. This paper discusses the environmental
      degradation in Mongolia and the social, economic and atmospheric impacts of dust
      storms in the sink area. The impact of dust storms on environmental compartments
      as well as their direct and indirect consequences to basic resources like water
      and energy demand and supply is explained. Governments are encouraged to take
      appropriate action in specified regions. For monitoring dust storms there is a
      need for international cooperation to combat growing environmental and human
      security concerns.

PMID- 16572292
TI  - Noninvasive identification of the unstable carotid plaque.
AB  - Intraplaque hemorrhage, enlarging lipid cores, and their proximity to the flow
      lumen are important determinants of carotid plaque rupture and neurological
      complications. We developed an image-analysis method for B-mode ultrasound, pixel
      distribution analysis (PDA), for preprocedural identification of these high-risk
      features in carotid plaques. This technique may improve selection of patients for
      carotid endarterectomy and carotid artery stenting. Forty-two patients with high
      grade carotid stenosis in 45 arteries, 18 symptomatic and 27 asymptomatic,
      underwent preoperative ultrasound. Intraplaque hemorrhage, lipid, fibromuscular
      tissue, calcium, lipid core area, and distance from the flow lumen were
      quantified using pixel intensities of tissues in control subjects. These findings
      were contrasted between symptomatic and asymptomatic plaques and correlated with
      histology. Inter- and intraobserver variabilities were determined for this
      technique. Pixel intensities of control tissues were discrete and significantly
      different from each other (median: blood 0, lipid 27, muscle 45.5, fibrous tissue
      204, and calcium 245). There was more intraplaque hemorrhage (p<0.001) and lipid
      (p=0.002) but less calcium (p<0.001) within symptomatic plaques. Lipid cores were
      larger (p=0.005) and their distance from the flow lumen was lower (p=0.01) in
      symptomatic plaques. Intraplaque hemorrhage, lipid, fibromuscular tissue,
      calcium, lipid core size, and distance from flow lumen measured by PDA correlated
      with histology. No significant inter- or intraobserver variabilities were
      observed in these measurements. PDA accurately identified more intraplaque
      hemorrhage and lipid, less calcium, and larger lipid cores located closer to the
      flow lumen in symptomatic patients with carotid stenosis. These data indicate
      that PDA may be used to identify high-risk carotid atherosclerotic plaques and
      thereby improve the selection of patients requiring treatment.

PMID- 16572294
TI  - Texture analysis for mapping Tamarix parviflora using aerial photographs along
      the Cache Creek, California.
AB  - Natural color photographs were used to detect the coverage of saltcedar, Tamarix
      parviflora, along a 40 km portion of Cache Creek near Woodland, California.
      Historical aerial photographs from 2001 were retrospectively evaluated and
      compared with actual ground-based information to assess accuracy of the
      assessment process. The color aerial photos were sequentially digitized,
      georeferenced, classified using color and texture methods, and mosaiced into maps
      for field use. Eight types of ground cover (Tamarix, agricultural crops, roads,
      rocks, water bodies, evergreen trees, non-evergreen trees and shrubs (excluding
      Tamarix)) were selected from the digitized photos for separability analysis and
      supervised classification. Due to color similarities among the eight cover types,
      the average separability, based originally only on color, was very low. The
      separability was improved significantly through the inclusion of texture
      analysis. Six types of texture measures with various window sizes were evaluated.
      The best texture was used as an additional feature along with the color, for
      identifying Tamarix. A total of 29 color photographs were processed to detect
      Tamarix infestations using a combination of the original digital images and
      optimal texture features. It was found that the saltcedar covered a total of 3.96
      km(2) (396 hectares) within the study area. For the accuracy assessment, 95
      classified samples from the resulting map were checked in the field with a global
      position system (GPS) unit to verify Tamarix presence. The producer's accuracy
      was 77.89%. In addition, 157 independently located ground sites containing
      saltcedar were compared with the classified maps, producing a user's accuracy of
      71.33%.

PMID- 16572295
TI  - Ab initio simulations of desorption and reactivity of glycine at a water-pyrite
      interface at "iron-sulfur world" prebiotic conditions.
AB  - Glycine at the interface of a pyrite surface (001) FeS2, and bulk water at high
      pressure and temperature conditions relevant to the "iron-sulfur world" scenario
      of the origin of life is investigated by theoretical means. Car-Parrinello
      molecular dynamics is used in order to study the desorption process of the
      zwitterionic form of this amino acid using two different adsorption modes, where
      either only one or both oxygens of the carboxylate group are anchored to surface
      iron atoms. It is found that the formation of stabilizing hydrogen bonds plays a
      key role in the detachment process, leading to longer retention times for the
      bidentate adsorption mode. In addition, the chemical reactivity of this
      heterogeneous system is probed by calculating the Fukui functions as site
      specific reactivity indices. The most prominent targets for both nucleophilic and
      electrophilic reactions to occur are surface atoms, whereas the reactivity of
      glycine is only slightly affected upon anchoring.

PMID- 16572296
TI  - Cytochrome P450-mediated metabolism of xanthotoxin by Papilio multicaudatus.
AB  - Within the genus Papilio, the P. glaucus group contains the most polyphagous
      Papilio species within the Papilionidae. The majority of Papilio species are
      associated with hostplants in the families Rutaceae and Apiaceae, and
      characterizing most are secondary metabolites called furanocoumarins. Recent
      phylogenetic studies suggest that furanocoumarin metabolism is an ancestral
      trait, with the glaucus group derived from ancestors associated with
      furanocoumarin-containing Rutaceae. In this study, we examined this relationship
      by conducting a gravimetric analysis of growth that used various concentrations
      of the furanocoumarin xanthotoxin. Papilio multicaudatus, the putative ancestor
      of the glaucus group, includes at least one furanocoumarin-containing rutaceous
      species among its hostplants; this species can consume leaf tissue containing up
      to 0.3% xanthotoxin with no detectable effect on relative growth rate, relative
      consumption rate, or efficiency of conversion of ingested food. As is the case
      for other Papilio species, xanthotoxin metabolism is mediated by cytochrome P450
      monooxygenases (P450s). Ingestion of xanthotoxin by ultimate instar P.
      multicaudatus increases activity up to 30-fold in a dose-dependent fashion.
      Midguts of induced larvae can also effectively metabolize six other
      furanocoumarins, including both linear (bergapten, isopimpinellin, imperatorin)
      and angular (angelicin, sphondin) forms. A metabolite of xanthotoxin in the frass
      from xanthotoxin-treated larvae, identified as 6-(7-hydroxy-8-methoxycoumaryl)
      acetic acid by MS-MS and NMR analyses, is identical to one from the frass of P.
      polyxenes. The occurrence of this metabolite in two swallowtails and the presence
      of a second metabolite of xanthotoxin, 6-(7-hydroxy-8-methoxycoumaryl)
      hydroxyethanol in the frass of both P. polyxenes and Depressaria pastinacella are
      consistent with the suggestion that lepidopterans share as the first step of
      xanthotoxin metabolism the P450-mediated epoxidation of the furan ring 2'-3'
      double bond.

PMID- 16572297
TI  - Where did the chili get its spice? Biogeography of capsaicinoid production in
      ancestral wild chili species.
AB  - The biogeography of pungency in three species of wild chili in the chaco and
      surrounding highland habitats of southeastern Bolivia is described. We report
      that Capsicum chacoense, C. baccatum, and C. eximium are polymorphic for
      production of capsaicin and its analogs, such that completely pungent and
      completely nonpungent individuals co-occur in some populations. In C. chacoense,
      the density of plants and the proportion of pungent plants increased with
      elevation. Above 900 m, all individuals in all populations except two were
      pungent; nonpungent individuals in at least one of the two polymorphic
      populations were likely a result of spreading by humans. The occurrence of
      pungent and nonpungent individuals in three species of ancestral Capsicum and the
      geographic variation of pungency within species suggest that production of
      capsaicin and its analogs entails both costs and benefits, which shift from one
      locality to another. Determining the selection pressures behind such shifts is
      necessary to understand the evolution of pungency in chilies.

PMID- 16572298
TI  - Diel periodicity in the production of green leaf volatiles by wild and cultivated
      host plants of stemborer moths, Chilo partellus and Busseola fusca.
AB  - The volatile chemicals produced by four poaceous plant species, blue thatching
      grass, Hyparrhenia tamba, Napier grass, Pennisetum purpureum, sorghum, Sorghum
      bicolor, and maize, Zea mays, which are host plants for the lepidopterous
      stemborers, Chilo partellus and Busseola fusca, were collected by air entrainment
      and analyzed by gas chromatography. The total quantities of volatiles collected
      hourly, over a 9-hr period, from P. purpureum and H. tamba showed an
      approximately hundredfold increase in the first hour of the scotophase.
      Thereafter, the amount decreased rapidly to levels present during photophase.
      Although onset of scotophase also triggered an increase in quantities of
      volatiles collected from two cultivars of S. bicolor and two out of three
      cultivars of Z. mays, these increases were less dramatic than in the two wild
      grasses, being only up to 10 times as much as in the last hour of photophase.
      Analysis showed that up to 95% of the increase in volatiles at the onset of the
      scotophase was due to just four compounds, the green leaf volatiles hexanal, (E)
      2-hexenal, (Z)-3-hexen-1-ol, and (Z)-3-hexen-1-yl acetate, with the latter
      dominating the volatile profile. Volatiles from P. purpureum were also collected
      at 10-min intervals for 70 min spanning the transition from light to dark. The
      vast increase in production of the green leaf volatiles in this species occurs in
      the first 10 min of the scotophase followed by a rapid decline within the next 20
      min. The relevance of these results to the control of stemborers in a "push-pull"
      strategy is discussed.

PMID- 16572299
TI  - Newly hatched neonate larvae can glycosylate: the fate of Betula pubescens bud
      flavonoids in first instar Epirrita autumnata.
AB  - Betula pubescens bud flavonoid aglycones reportedly have negative effects on the
      performance of first instar Epirrita autumnata and, thus, may defend birch leaves
      from larval defoliation. We hypothesized that the detrimental effects of these
      lipophilic flavonoids on larvae are due to their high levels in birch buds and/or
      the inability of naive neonates to glycosylate them, which we have shown to occur
      in fifth instars. To test the latter hypothesis, we investigated the biochemical
      transformation of bud flavonoids in first instar E. autumnata. We found that
      newly hatched larvae have the ability to glycosylate birch bud/leaf flavonoid
      aglycones into corresponding glycosides. Moreover, we suggest that glycosylation
      may depend upon the chemical character of the aglycone and is an important factor
      in the performance of first instars.

PMID- 16572300
TI  - The mediational role of neurocognition in the behavioral outcomes of a social
      emotional prevention program in elementary school students: effects of the PATHS
      Curriculum.
AB  - Neuropsychology is one field that holds promise in the construction of
      comprehensive, developmental models for the promotion of social competence and
      prevention of problem behavior. Neuropsychological models of behavior suggest
      that children's neurological functioning affects the regulation of strong
      emotions, as well as performance in social, cognitive, and behavioral spheres.
      The current study examines the underlying neurocognitive conceptual theory of
      action of one social-emotional development program. Hypothesized was that
      inhibitory control and verbal fluency would mediate the relationship between
      program condition and teacher-reported externalizing and internalizing behavior
      problems. Participants were 318 regular education students enrolled in the second
      or third grade. A series of regression analyses provided empirical support for
      (a) the effectiveness of the PATHS Curriculum in promoting inhibitory control and
      verbal fluency and (b) a partial mediating role for inhibitory control in the
      relation between prevention condition and behavioral outcomes. Implications are
      that programs designed to promote social and emotional development should
      consider comprehensive models that attend to neurocognitive functioning and
      development. Lack of consideration of neurocognitive pathways to the promotion of
      social competence may ignore important mechanisms through which prevention
      affects youth outcomes. Furthermore, the findings suggest that developers of
      social-emotional preventions should design curricula to explicitly promote the
      developmental integration of executive functioning, verbal processing, and
      emotional awareness. Doing so may enhance prevention outcomes particularly if
      those preventions are implemented during a time of peak neurocognitive
      development.

PMID- 16572301
TI  - The role of behavior observation in measurement systems for randomized prevention
      trials.
AB  - The role of behavior observation in theory-driven prevention intervention trials
      is examined. A model is presented to guide choice of strategies for the
      measurement of five core elements in theoretically informed, randomized
      prevention trials: (1) training intervention agents, (2) delivery of key
      intervention conditions by intervention agents, (3) responses of clients to
      intervention conditions, (4) short-term risk reduction in targeted client
      behaviors, and (5) long-term change in client adjustment. It is argued that the
      social processes typically thought to mediate interventionist training (Element
      1) and the efficacy of psychosocial interventions (Elements 2 and 3) may be
      powerfully captured by behavior observation. It is also argued that behavior
      observation has advantages in the measurement of short-term change (Element 4)
      engendered by intervention, including sensitivity to behavior change and blinding
      to intervention status.

PMID- 16572302
TI  - Mediators and moderators of parental involvement on substance use: a national
      study of adolescents.
AB  - Current social developmental theories of drug use often incorporate mediation
      processes, but it is generally unknown whether these mediation processes
      generalize across ethnicity and gender. In the present study, we developed a
      mediation model of substance use based on current theory and research and then
      tested the extent to which the model was moderated by gender and ethnicity
      (African American, European American, and Hispanic American), separately for 8th
      and 10th graders. The respondents were adolescents from the 1994, 1995, and 1996
      cohorts of the Monitoring the Future (MTF) project, which conducts yearly in
      school surveys with nationally representative samples. Multi-group, structural
      equation modeling (SEM) results indicated much similarity across gender and
      ethnicity for school success and time spent with friends as partial mediators of
      risk taking and parental involvement on drug use (controlling for parental
      education). However, there were some differences in the magnitude of indirect
      effects of parental involvement and risk taking on substance use for 8th-grade
      African American girls. Discussion focuses on the potential success of prevention
      efforts across different ethnicities and gender that target parent-child
      relationship improvement and risk taking, and considers possible culture- and
      gender-specific issues.

PMID- 16572303
TI  - Feasibility of in vivo dual-energy myocardial SPECT for monitoring the
      distribution of transplanted cells in relation to the infarction site.
AB  - PURPOSE: Cell therapy using bone marrow mesenchymal stem cells (BMSCs) shows
      promise in the treatment of myocardial infarction (MI) but accurate cell delivery
      within MI areas remains critical. In the present study, we tested the feasibility
      of in vivo pinhole SPECT imaging for monitoring the sites of intramyocardial
      implanted BMSCs in relation to targeted MI areas in rats. METHODS: BMSCs were
      labelled with (111)In-oxine and injected within the fibrotic areas of 3-month-old
      MI in ten rats. Two days later, dual (111)In/(99m)Tc-sestamibi pinhole SPECT was
      recorded for localisation of (111)In-BMSCs on a 15-segment left ventricular (LV)
      division. Additional (99m)Tc-sestamibi pinhole SPECT had been performed 1 month
      earlier and on the day before transplantation. In vitro counting on histological
      sections was used to validate the pinhole SPECT determination of (111)In-BMSC
      activity within LV segments. RESULTS: The underperfused MI area (segments with
      <70% uptake) was stable between the (99m)Tc-sestamibi SPECT study recorded at 1
      month (4.6+/-1.9 segments) and at 1 day (4.7+/-2.3 segments) before
      transplantation. (111)In-BMSCs were detected by dual-energy SPECT in 56 segments:
      33 (59%) were underperfused MI segments but 23 (41%) were not (14 adjacent and
      nine remote segments). Finally, (111)In-labelled BMSCs were not detected in 14
      out of the 47 (30%) underperfused MI segments. CONCLUSION: When BMSCs are
      injected within MI areas in rats, sites of early cell retention do not always
      match the targeted MI areas. The dual-energy pinhole SPECT technique may be used
      for monitoring the sites of early retention of implanted BMSCs and the data
      obtained may have critical importance when analysing the effects of cardiac cell
      therapy.

PMID- 16572304
TI  - Role of FDG-PET and PET/CT in the diagnosis of prolonged febrile states.
AB  - PURPOSE: The role of FDG-PET and PET/CT in patients whose main symptom is
      prolonged fever has not yet been defined. We addressed this topic in a
      retrospective study. METHODS: A total of 124 patients (referred between May 2001
      and December 2004) with fever of unknown origin or prolonged fever due to a
      suspected infection of a joint or vascular prosthesis were included in the study.
      The patients underwent either FDG-PET or FDG-PET/CT scanning. Sixty-seven
      patients had a negative focal FDG-PET finding; in this group the method was
      regarded as unhelpful in determining a diagnosis, and no further investigation
      was pursued. We tried to obtain clinical confirmation for all patients with
      positive PET findings. RESULTS: Fifty-seven (46%) patients had positive FDG-PET
      findings. In six of them no further clinical information was available. Fifty-one
      patients with positive PET findings and 118 patients in total were subsequently
      evaluated. Systemic connective tissue disease was confirmed in 17 patients,
      lymphoma in three patients, inflammatory bowel disease in two patients, vascular
      prosthesis infection in seven patients, infection of a hip or knee replacement in
      seven patients, mycotic aneurysm in two patients, abscess in four patients and
      AIDS in one patient. In eight (16%) patients the finding was falsely positive.
      CONCLUSION: FDG-PET or PET/CT contributed to establishing a final diagnosis in
      84% of the 51 patients with positive PET findings and in 36% of all 118 evaluated
      patients with prolonged fever.

PMID- 16572305
TI  - 123/125I-labelled 2-iodo-L: -phenylalanine and 2-iodo-D: -phenylalanine:
      comparative uptake in various tumour types and biodistribution in mice.
AB  - PURPOSE: In vitro in the R1M cell model and in vivo in the R1M tumour-bearing
      athymic model, both [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: 
      phenylalanine have shown promising results as tumour diagnostic agents for SPECT.
      In order to compare these two amino acid analogues and to examine whether the
      observed characteristics could be generalised, both isomers were evaluated in
      various tumour models. METHODS: Transport type characterisation in vitro in A549,
      A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M cells with [(123)I]-2-iodo-L: 
      phenylalanine was performed using the method described by Shotwell et al.
      Subsequently, [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: 
      phenylalanine tumour uptake and biodistribution were evaluated using dynamic
      planar imaging and/or dissection in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29
      and R1M inoculated athymic mice. Two-compartment blood modelling of the imaging
      results was performed. RESULTS: In vitro testing demonstrated that [(123)I]-2
      iodo-L: -phenylalanine was transported in all tumour cell lines by LAT1. In all
      tumour models, the two amino acid analogues showed the same general
      biodistribution characteristics: high and specific tumour uptake and renal tracer
      clearance. Two-compartment modelling revealed that the D: -isomer showed a faster
      blood clearance together with a faster distribution to the peripheral compartment
      in comparison with [(123)I]-2-iodo-L: -phenylalanine. CONCLUSION: [(123)I]-2-iodo
      L: -phenylalanine and its D: -isomer are promising tumour diagnostic agents for
      dynamic planar imaging. They showed a high and similar uptake in all tested
      tumours. [(123)I]-2-iodo-D: -phenylalanine showed better tracer characteristics
      concerning radiation dose to other organs.

PMID- 16572306
TI  - A phase 2 study of high-activity 186Re-HEDP with autologous peripheral blood stem
      cell transplant in progressive hormone-refractory prostate cancer metastatic to
      bone.
AB  - PURPOSE: We investigated the potential for improvement in disease control by use
      of autologous peripheral blood stem cell transplant (PBSCT) to permit
      administration of high activities of (186)Re-hydroxyethylidene diphosphonate
      (HEDP) in patients with progressive hormone-refractory prostate cancer (HRPC).
      METHODS: Eligible patients had progressive HRPC metastatic to bone, good
      performance status and minimal soft tissue disease. Patients received 5,000 MBq
      of (186)Re-HEDP i.v., followed 14 days later by PBSCT. Response was assessed
      using PSA, survival, pain scores and quality of life. RESULTS: Thirty-eight
      patients with a median age of 67 years (range 50-77) and a median PSA of 57 ng/ml
      (range 4-3,628) received a median activity of 4,978 MBq (186)Re-HEDP (range 4,770
      5,100 MBq). The most serious toxicity was short-lived grade 3 thrombocytopenia in
      8 (21%) patients. The median survival of the group is 21 months (95%CI 18-24
      months) with Kaplan-Meier estimated 1- and 2-year survival rates of 83% and 40%
      respectively. Thirty-one patients (81%, 95% CI 66-90%) had stable or reduced PSA
      levels 3 months post therapy while 11 (29%, 95% CI 15-49%) had PSA reductions of
      >50% lasting >4 weeks. Quality of life measures were stable or improved in 27
      (66%) at 3 months. CONCLUSION: We have shown that it is feasible and safe to
      deliver high-activity radioisotope therapy with PBSCT to men with metastatic
      HRPC. Response rates and survival data are encouraging; however, further research
      is needed to define optimal role of this treatment approach.

PMID- 16572307
TI  - Treatment of SVC syndrome and hemoptysis in a patient with mediastinal fibrosis.
AB  - Mediastinal fibrosis can present with a multitude of symptoms, most commonly
      cough, dyspnea and hemoptysis. We describe a case of mediastinal fibrosis
      secondary to histoplasmosis, which presented with both superior vena cava
      syndrome (SVCS) and hemoptysis. Our patient was successfully treated with
      bronchial artery embolization followed by SVC stent placement during a brief
      hospital stay.

PMID- 16572310
TI  - Successful treatment of septic shock due to pan-resistant Acinetobacter baumannii
      using combined antimicrobial therapy including tigecycline.
AB  - Reported here is the case of a patient with septic shock due to multidrug
      resistant Acinetobacter baumannii, which developed after complicated acute
      pancreatitis with intra-abdominal abscess. Treatment with colistin
      methanesulphonate and high doses of meropenem were initiated, but since shock
      persisted, tigecycline was added to the regimen, resulting in successful
      resolution of the infection.

PMID- 16572308
TI  - Cloricromene, a coumarine derivative, reduced the development of periodontitis in
      rats.
AB  - Recent studies have demonstrated that cloricromene, a coumarin derivative, exerts
      protective effects in models of inflammation and shock. Tumour necrosis factor
      plays a pivotal role in the induction of genes involved in physiological
      processes, as well as in the response to inflammation. We investigated the effect
      of cloricromene in a rat model of periodontitis. Periodontitis was induced in
      rats by placing a 2/0 braided silk ligature around the lower left first molar. At
      day 8 the gingivomucosal tissue encircling the mandibular first molar was removed
      for evaluation of tumour necrosis factor production, neutrophil infiltration,
      tissue permeability, nitrotyrosine formation, poly (ADP-ribose) polymerase
      activation, radiography and histology. Ligation significantly induced an
      increased tumour necrosis factor production, neutrophil infiltration and a
      positive staining for nitrotyrosine formation and poly (ADP-ribose) polymerase
      activation. Ligation significantly increased Evans blue extravasation in
      gingivomucosal tissue and alveolar bone erosion as evaluated by radiography
      analysis. Intraperitonal injection of cloricromene (10 mg/kg daily for 8 days)
      significantly decreased all of the parameters of inflammation as described above.
      This suggests that cloricromene treatment, which reduced tumour necrosis factor
      production, may be of benefit in the treatment of periodontitis.

PMID- 16572309
TI  - Impairment of endothelium- and nerve-mediated relaxation responses in the
      cavernosal smooth muscle of experimentally diabetic rabbits: role of weight loss
      and duration of diabetes.
AB  - The effects of short- and long-term experimental diabetes on corporal nerve,
      endothelium and smooth-muscle responses were investigated, and the reasons for
      possible alterations in corporal smooth muscle responses such as hyperglycaemia,
      duration of experimental diabetes and/or altered tissue weight were evaluated.
      Rabbits were injected with alloxan (125 mg/kg) to induce diabetes. Age-matched
      non-diabetic and diabetic (3 and 9 weeks) and weight-matched non-diabetic groups
      (9 weeks) were used as control. In all groups, relaxation (carbachol, electrical
      field stimulation and sodiumnitroprusside) responses were examined. The
      relaxation responses were expressed as percentage of the precontraction to
      phenylephrine and as g response/g tissue weight. The effects of elevated glucose
      were also examined by incubating cavernosal strips in Krebs-Henseleit solution
      containing 44.4 mM glucose for 6 h. Cavernosal tissues of non-diabetic and 9-week
      diabetic rabbits were evaluated histologically. Sodiumnitroprusside (10(-7)-10(
      4) M) responses were similar in all groups. Relaxation responses to electrical
      field stimulation (10 s train; amplitude 50 V; frequency 0.5-32 Hz; width 0.8 ms)
      were only attenuated in the 9-week diabetic group compared to the non-diabetic
      group. Carbachol (10(-8)-3 x 10(-5) M) responses were attenuated in both diabetic
      groups. When the relaxation responses expressed as g response/g tissue weight
      were evaluated, results were similar compared to those expressed as percentage of
      phenylephrine (10(-5) M). Neither carbachol nor electrical field stimulation
      mediated responses were impaired with glucose incubation. No morphological
      degenerations were observed in the endothelium. Diabetes may interfere with the
      synthesis and/or release of nitric oxide from both nerves and endothelium in
      corpus cavernosum, and alterations in endothelium-derived responses occur earlier
      than neurological disturbances. The sensitivity of cavernosal smooth muscle to
      nitric oxide did not alter in diabetes. Attenuation of responses was not due to
      decreased tissue weight caused by diabetes.

PMID- 16572311
TI  - Mucositis guidelines: what have they achieved, and where to from here?

PMID- 16572312
TI  - Progressive disease in patients with cancer presenting to an emergency room with
      acute symptoms predicts short-term mortality.
AB  - GOALS: Patients with symptomatic, advanced cancer continue to be referred late or
      not at all for hospice or palliative care. We conducted a retrospective cohort
      study to determine whether evidence of cancer progression is an independent
      predictor of short-term mortality in acutely symptomatic cancer patients.
      PATIENTS AND METHODS: We reviewed the records of 396 patients who visited the
      emergency center at a comprehensive cancer center in January 2000. Records were
      reviewed for clinical characteristics, including symptoms, type and extent of
      cancer, and whether the patient's cancer was stable or progressing (uncontrolled)
      at the time of the emergency center visit. Cox regression analysis was used to
      assess survival at 90 and 180 days, after controlling for patient
      characteristics. MAIN RESULTS: Patients who died within 14, 90, or 180 days were
      more likely to have disease progression than those who did not. Dyspnea on
      emergency center presentation and disease progression were independent predictors
      of death within 90 or 180 days, after controlling for patient age, symptoms,
      signs, and the presence of metastases. The odds ratios for death within 90 and
      180 days were 3.97 and 4.34, respectively (95% confidence intervals: 1.44, 10.94
      and 1.87, 10.09). CONCLUSION: Cancer disease progression is a clinical measure of
      increased risk of short-term mortality in acutely symptomatic cancer patients.
      Future studies should examine whether the use of this characteristic enhances
      identification of patients who could benefit from timely referral to hospice or
      palliative care. Symptomatic cancer patients presenting to a cancer center
      emergency room were more likely to die within 14, 90, or 180 days if they had
      evidence of recent progression of their cancer. Among patients with disease
      progression, 47% died within 90 days and 61% within 180 days.

PMID- 16572313
TI  - The role of alternative and natural agents, cryotherapy, and/or laser for
      management of alimentary mucositis.
AB  - GOALS OF WORK: To review the literature and update the current guidelines of
      alternative/natural agents, cryotherapy, and/or laser therapy in the management
      of alimentary mucositis (AM). MATERIALS AND METHODS: The original guidelines
      developed by the Multinational Association for Supportive Care in Cancer
      (MASCC)/International Society for Oral Oncology (ISOO) mucositis study group were
      the basis for this study. A medical librarian conducted an initial Medline search
      to identify research articles published between 2002 and 2005 in English
      language. A search term combination that included stomatitis, mucositis, mucous
      membrane, neoplasm, lasers, complimentary therapies, amino acids, antioxidants,
      vitamins, minerals, plant extracts, and cryotherapy was conducted. This initial
      search identified articles with a strong scientific methodology that included
      both preclinical and clinical research. Using standardized scoring forms, authors
      reviewed and scored individual articles. A consensus result of the review was
      achieved in a meeting of reviewers in June of 2005. RESULTS: The initial search
      identified a total of 167 new articles. Of these, 14 were selected and reviewed:
      alternative/natural therapy (one preclinical study); cryotherapy (four clinical
      studies); lasers (two clinical studies); and alternative/natural agents (seven
      clinical studies). A new guideline could be established for the use of
      cryotherapy in the management of AM in hematopoietic stem cell transplant (HSCT)
      patients receiving melphalan in the conditioning phase. CONCLUSION: The rapid
      progress in the understanding of AM created a need for new prevention and
      management protocols. Frequent literature review is now necessary to identify
      agents and protocols being developed in this important area of supportive care in
      cancer.

PMID- 16572314
TI  - Ways of understanding the encounter with head and neck cancer patients in the
      hospital dental team--a phenomenographic study.
AB  - INTRODUCTION: Head and neck cancer is the sixth most common malignancy in the
      world. Fifty percent of the patients can be cured by surgery, radiotherapy or a
      combination approach. Head and neck cancer is life-threatening, and treatment may
      leave the patient with visible facial disfigurements and impairment of functions
      such as speech and eating. This affects not only the patient, but may arouse
      difficult feelings in the treatment staff. Dental personnel are involved in all
      facets of treatment, yet they have no specific training in cancer care.
      BACKGROUND: The aim of this study was to describe the variation in ways dental
      personnel understand and experience the encounter with head and neck cancer
      patients, as the way of understanding a certain phenomenon is judged to be
      fundamental to the way we act and form our beliefs. METHODS: Twenty members of
      hospital dental teams were interviewed. The interviews focused on experiences of
      the encounter with head and neck cancer patients. A qualitative research
      approach, phenomenography, was used in analysing the interviews. The encounter
      was perceived in three qualitatively different ways: as an act of caring, as a
      serious and responsible task and as an overwhelming emotional situation. The
      results indicate that hospital dental personnel are not able to lean on education
      and professional training in finding ways of dealing with situations with strong
      emotional impact. This has implications for the treatment of patients with head
      and neck cancer, as well as education of dental personnel.

PMID- 16572315
TI  - A comparative study of living conditions in cancer patients who have returned to
      work after curative treatment.
AB  - GOALS OF WORK: The goal of this study was to explore living conditions among
      disease-free cancer survivors participating in the labour force after successful
      primary treatment. Their living conditions were compared with the conditions of
      matched controls from the general Norwegian population. PATIENTS AND METHODS:
      Living conditions are social indicators that stimulate social inclusion and
      reduce exclusion such as economy, employment, health, housing and social
      participation. A questionnaire covering living conditions with established
      questions from population surveys was mailed to 852 cancer survivors and 1,548
      controls. Valid responses were obtained from 51% cancer survivors (216 women with
      breast cancer, 49 men with prostate cancer, and 165 with testicular cancer) and
      39% controls (317 women and 279 men). MAIN RESULTS: Compared to their controls
      cancer survivors showed no difference in work hours or full-time jobs, but
      reported significantly poorer physical and mental work capacity. This was
      associated with significantly more somatic diseases among survivors and poorer
      general health status in male survivors. The survivors had significantly smaller
      households and more living space than controls. No significant differences were
      observed concerning economy or social participation, except that significantly
      more female survivors than controls stated that they had enough friends.
      CONCLUSIONS: In spite of poorer health, tumour-free survivors after breast,
      testicular, and prostate cancer report mostly equal living conditions compared to
      matched controls. The protection hypothesis of holding jobs as a precondition for
      normal living condition was confirmed in our study of a sample of cancer
      survivors with good outcome.

PMID- 16572316
TI  - Scoring the effect of radiotherapy for painful bone metastases.
AB  - RATIONALE: The evaluation of the analgesic effects of radiotherapy in painful
      bone metastases is a matter of controversies due to a lack of appropriate tools
      to define the outcome. An integration of competences in monitoring the pain
      response and modifying the opioid treatment according to changes of the clinical
      condition is mandatory. PROPOSED METHOD: A meaningful score, used in previous
      works to monitor the global response to an analgesic intervention in advanced
      cancer patients, is proposed. A case report, in which opioids are first titrated
      and then tapered, is described as an example of application of this method.

PMID- 16572317
TI  - [Muscle biomechanics in total ankle replacement].
AB  - The purpose of this orthopaedic-biomechanical study was to evaluate the muscle
      function in total ankle replacement (TAR) patients 1 year after surgery. Ten
      patients underwent a combined clinical and muscle biomechanical assessment prior
      to implantation and at the 1-year follow-up. Pain score, American Orthopaedic
      Foot and Ankle Society (AOFAS) ankle score, ankle range of motion (ROM), and calf
      circumference difference between the affected leg and contralateral healthy leg
      were assessed. Biomechanically, isometric maximal voluntary torque for ankle
      dorsiflexion and plantar flexion was measured simultaneously with surface
      electromyography of four lower leg muscles. At follow-up, a significant
      improvement of the pain score (from 6.7 to 0.8 points), AOFAS ankle score (from
      35.6 to 92.3 points), and ROM could be shown. Not significantly, the mean calf
      circumference difference between legs decreased from 2.2 to 1.4 cm. However, a
      significant increase was seen in the mean dorsiflexion (from 17.0 to 25.8 Nm) and
      plantar flexion torque (15.7 to 24.6 Nm) of the TAR-treated ankle. The mean EMG
      frequency content of the affected lower leg at TAR follow-up was lower than in
      the muscles of the contralateral healthy side. In contrast, the mean EMG
      intensity at TAR follow-up in side-comparison was statistically the same for all
      muscles. Ankle OA patients have better muscle function with TAR than under the
      arthritic condition, but they do not reach the normal level of the contralateral
      healthy leg 1 year after surgery.

PMID- 16572318
TI  - [The influence of jet-lavage systems on in vitro cement penetration].
AB  - The benefit of pulsatile lavage on cement penetration in femoral cancellous bone
      is well known. The aim of this study was to determine the influence of different
      jet-lavage systems on cement penetration in a standardized cadaver study. Four
      different jet-lavage systems were compared (right vs left) in 30 paired human
      femora. After broaching, the femoral canal was lavaged with 1 l saline. The
      specimens were embedded in plastic pots, bone cement was applied in a retrograde
      manner and cement was pressurized using a standard pressure protocol with a
      constant force of 3,000 N. Horizontal sections were obtained at predefined levels
      using an automatic saw. Microradiographs were taken and analysed using image
      analysis to assess the extent of cement penetration. There were no significant
      differences in cement penetration into cancellous bone using the different jet
      lavage systems. This technique is of great importance for obtaining a good
      interdigitation with cancellous bone. The different jet-lavage systems
      investigated in our study, however, seemed to be equally effective.

PMID- 16572319
TI  - Gene expression analyses reveal molecular relationships among 20 regions of the
      human CNS.
AB  - Transcriptional profiling was performed to survey the global expression patterns
      of 20 anatomically distinct sites of the human central nervous system (CNS).
      Forty-five non-CNS tissues were also profiled to allow for comparative analyses.
      Using principal component analysis and hierarchical clustering, we were able to
      show that the expression patterns of the 20 CNS sites profiled were significantly
      different from all non-CNS tissues and were also similar to one another,
      indicating an underlying common expression signature. By focusing our analyses on
      the 20 sites of the CNS, we were able to show that these 20 sites could be
      segregated into discrete groups with underlying similarities in anatomical
      structure and, in many cases, functional activity. These findings suggest that
      gene expression data can help define CNS function at the molecular level. We have
      identified subsets of genes with the following patterns of expression: (1) across
      the CNS, suggesting homeostatic/housekeeping function; (2) in subsets of
      functionally related sites of the CNS identified by our unsupervised learning
      analyses; and (3) in single sites within the CNS, indicating their participation
      in distinct site-specific functions. By performing network analyses on these gene
      sets, we identified many pathways that are upregulated in particular sites of the
      CNS, some of which were previously described in the literature, validating both
      our dataset and approach. In summary, we have generated a database of gene
      expression that can be used to gain valuable insight into the molecular
      characterization of functions carried out by different sites of the human CNS.

PMID- 16572320
TI  - A small economic inducement to stimulate increased reporting of adverse drug
      reactions--a way of dealing with an old problem?
AB  - PURPOSE: To assess the effect of a small economic inducement on the rate of
      spontaneous reporting of adverse drug reactions (ADRs) and the attitudes of
      general practitioners and physicians towards reporting of ADRs. METHOD: One
      intervention and one control county were selected for the study. Written
      information about the main purpose of spontaneous reporting of ADRs was
      personally addressed to all physicians in the two counties. The information was
      identical, except for the addition that during a period of 6 months two lottery
      tickets would be given to the receivers in the intervention area with the
      standard personal feedback to the reporter of the ADR. After the 6-month study
      period, the actual number of reported ADRs and the seriousness of the reported
      ADRs were assessed. To investigate the attitude towards this stimulation of
      reporting, a questionnaire was addressed to all physicians within the
      intervention area (IA). RESULTS: From the IA a total number of 57 ADR reports
      were received containing 62 suspected ADRs, 40% of which were assessed as serious
      reactions. From the control area (CA), 49 reports containing 50 suspected ADRs
      were received, 32% of which were assessed as serious reactions. The increase of
      ADR reports from the IA compared to the same time period the previous year was
      59% as compared to an unchanged reporting from the CA. Of those responding to the
      questionnaire, 80% did not believe that a small economic bonus would be a useful
      tool to improve the reporting rate. CONCLUSION: A small economic inducement is
      associated with an increase in the reporting of suspected ADRs.

PMID- 16572321
TI  - Study of Cynomolgus monkey (Macaca fascicularis) MhcDRB (Mafa-DRB) polymorphism
      in two populations.
AB  - Cynomolgus monkey is one of the macaque species currently used as an animal model
      for experimental surgery and medicine, in particular, to experiment new drugs or
      therapy protocols designed for the prevention of allograft rejection. In this
      field, it is of utmost importance to select histoincompatible recipient-donor
      pairs. One way to ensure incompatibility between donor and recipient is to check
      their major histocompatibility complex (MHC) genotypes at the loci playing a
      determinant role in histocompatibility. We report in this paper on the cynomolgus
      monkey DRB polymorphism evidenced by sequencing of amplified exon 2 separated
      either by denaturing gradient gel electrophoresis (DGGE), or by cloning. By the
      study of 253 unrelated animals from two populations (Mauritius and The
      Philippines), we characterized 50 exon 2 sequences among which 28 were identical
      to sequences already reported in Macaca fascicularis or other macaque species
      (Macaca mulatta, Macaca nemestrina). By cloning and sequencing DRB cDNA, we
      revealed two additional DRB alleles. Out of the 20 haplotypes that we defined
      here, only two were found in both populations. The functional impact of DR
      incompatibility was studied in vitro by mixed lymphocyte culture.

PMID- 16572323
TI  - Antiproliferative effect of indomethacin on CML cells is related to the
      suppression of STATs/Bcl-XL signal pathway.
AB  - Indomethacin (IN) can inhibit cyclooxygenase activity and is considered to exert
      antitumor action in a variety of cancer cells. In the present study, we
      investigated the underlying mechanism of its antiproliferative effect on chronic
      myeloid leukemia (CML) cells. We studied the role of signal transducer and
      activator of transcription 1 or 5 (STAT(1) or STAT(5)) and Bcl-X(L) proteins in
      IN-induced proliferative inhibition on CML cells. Both K562 cells and fresh bone
      marrow mononuclear cells from five CML patients were exposed to IN. Cell
      proliferation was determined by MTT assay. The expression of JAK(2), STAT(1),
      STAT(5), and Bcl-X(L) proteins was probed with Western blotting. The level of
      phosphorylated STAT(1) (p-STAT(1)) or STAT(5) (p-STAT(5)) proteins was determined
      by coimmunoprecipitation combined with Western blotting. Intracellular
      localizations of both STAT(1)/STAT(5) and p-STAT(1)/p-STAT(5) were observed by
      indirect immunofluorescence assay. Our results showed that IN could inhibit the
      proliferation of CML cells in a dose-dependent manner (36-288 microg/ml). The
      expression of STAT(1) and STAT(5) was suppressed by IN both in a concentration
      dependent manner and a time-dependent (0-36 h) manner. The levels of p-STAT(1)
      and p-STAT(5) were down-regulated by IN. A similar result was obtained for Bcl
      X(L) protein expression. The intracellular fluorescence signals representing
      STAT(1)/STAT(5) and p-STAT(1)/p-STAT(5) were obviously weakened by IN. In
      contrast with IN, granulocyte-macrophage colony-stimulating factor could
      significantly promote the growth of CML cells and up-regulate the expression of
      both STAT(1)/STAT(5) and p-STAT(1)/p-STAT(5). This data indicated that IN is able
      to suppress the proliferation of CML cells, and the mechanism is associated with
      the inhibition of STATs/ Bcl-X(L) signal transduction pathway.

PMID- 16572322
TI  - Visual pigments of marine carnivores: pinnipeds, polar bear, and sea otter.
AB  - Rod and cone visual pigments of 11 marine carnivores were evaluated. Rod,
      middle/long-wavelength sensitive (M/L) cone, and short-wavelength sensitive (S)
      cone opsin (if present) sequences were obtained from retinal mRNA. Spectral
      sensitivity was inferred through evaluation of known spectral tuning residues.
      The rod pigments of all but one of the pinnipeds were similar to those of the sea
      otter, polar bear, and most other terrestrial carnivores with spectral peak
      sensitivities (lambda(max)) of 499 or 501 nm. Similarly, the M/L cone pigments of
      the pinnipeds, polar bear, and otter had inferred lambda(max) of 545 to 560 nm.
      Only the rod opsin sequence of the elephant seal had sensitivity characteristic
      of adaptation for vision in the marine environment, with an inferred lambda(max)
      of 487 nm. No evidence of S cones was found for any of the pinnipeds. The polar
      bear and otter had S cones with inferred lambda(max) of approximately 440 nm.
      Flicker-photometric ERG was additionally used to examine the in situ
      sensitivities of three species of pinniped. Despite the use of conditions
      previously shown to evoke cone responses in other mammals, no cone responses
      could be elicited from any of these pinnipeds. Rod photoreceptor responses for
      all three species were as predicted by the genetic data.

PMID- 16572325
TI  - Opioids in pain management of blood-related malignancies.
AB  - Opioids are basic analgesics used in the treatment of moderate to severe pain in
      patients affected by blood-related malignancies. They should be sequentially
      administered according to the World Health Organisation scale for cancer pain.
      Initial treatment and titration with opioids should be based on immediate-release
      preparations, to be administered at appropriate intervals in order to relieve
      pain and to satisfy the individual opioid requirement. Once a relatively good
      pain control has been achieved, a slow release formulation at equivalent doses
      can be given. Most patients can be adequately managed using oral formulation
      opioids. However, a small group, such as those presenting severe mucositis or
      requiring a rapid pain relief, should be managed by intravenous continuous
      infusion and/or by a patient-controlled analgesia system; while for patients in
      the community, there are distinct advantages to using the subcutaneous route.
      Other available routes of administration for opioids, can be used in selected
      circumstances, including rectal, transdermal, epidural, intrathecal and
      intramuscular. The invasive neuraxial route has a very limited role in patients
      with haematological malignancies, given the high risk of infection and bleeding.
      Through a close observation and a careful management, opioid-related side effects
      can be effectively prevented and treated. This article reviews the principles of
      opioid therapy and how opioids can be adapted for patients with pain due to
      haematological malignancies.

PMID- 16572324
TI  - Perianal tuberculosis during neutropenia: a rare case report and review of
      literature.

PMID- 16572326
TI  - Paratial anomalous pulmonary venous connection in a patient with cardiac failure
      and sepsis.

PMID- 16572327
TI  - Systemic capsaicin inhibits neuronal activation in the brainstem during
      postoperative ileus in the mouse.
AB  - INTRODUCTION: Neuronal inhibitory reflex mechanisms contribute to postoperative
      ileus after abdominal surgery. During this condition, sensory neurons in the
      brainstem are activated. We aimed to determine the contribution of capsaicin
      sensitive afferents to central vagal sensitivity in mice during postoperative
      ileus. MATERIALS AND METHODS: Under enflurane anesthesia, C57BL/6 mice were
      laparotomized and the small bowel was manipulated to induce ileus or was left
      untouched as a sham-treatment group. A subgroup of ileus animals was pre-treated
      with Capsaicin (1 microm/kg, i.p.) 48 h before small bowel manipulation. The
      animals were killed 24 h later and the brainstem was removed for Fos
      immunohistochemistry, which was quantified in the nucleus of the solitary tract
      (nTS). Spontaneous jejunal motility was recorded in vitro. Leukocyte infiltration
      in the intestinal muscularis was studied by myeloperoxidase staining as an index
      of postoperative inflammation. RESULTS: There were 30+/-9 Fos-positive neurons
      counted in the nTS after ileus and 6+/-2 in sham controls (Bregma -7.70 mm,
      P=0.01). A reduction to 8+/-3 was observed after Capsaicin pre-treatment in ileus
      animals (P<0.05). Peak amplitudes of spontaneous jejunal motility were 2+/-0.3
      cmH2O during postoperative ileus, 3+/-0.6 cmH2O after ileus with capsaicin pre
      treatment, and 10+/-2 cmH2O in control animals (N=6, both P<0.05). The number of
      leukocytes infiltrating the muscularis was 39+/-9/mm2 during ileus and 1.8+/
      1/mm2 in controls (mean+/-SEM, P<0.01, N=6). After capsaicin, this number
      increased to 72+/-28/mm2 in ileus animals (P<0.05 vs control animals, N=7).
      CONCLUSION: The inhibition of capsaicin-sensitive vagal afferent pathways appears
      to boost rather than to attenuate the inflammatory response during postoperative
      ileus, while intestinal motility remained unchanged. This suggests a protective
      role of the capsaicin-sensitive afferent innervation for the inflammatory phase
      of postoperative ileus.

PMID- 16572328
TI  - Leadership characteristics and business management in modern academic surgery.
AB  - BACKGROUND: Management skills are necessary to successfully lead a surgical
      department in future. OBJECTIVE: This article focuses on practical aspects of
      surgical management, leadership and training. It demonstrates how the
      implementation of business management concepts changes workflow management and
      surgical training. METHODS: A systematic Medline search was performed and
      business management publications were analysed. RESULTS: Neither management nor
      leadership skills are inborn but acquired. Management is about planning,
      controlling and putting appropriate structures in place. Leadership is
      anticipating and coping with change and people, and adopting a visionary stance.
      More change requires more leadership. Changes in surgery occur with unprecedented
      speed because of a growing demand for surgical procedures with limited financial
      resources. Modern leadership and management theories have to be tailored to
      surgery. It is clear that not all of them are applicable but some of them are
      essential for surgeons. In business management, common traits of successful
      leaders include team orientation and communication skills. As the most important
      character, however, appears to be the emotional intelligence. Novel training
      concepts for surgeons include on-the-job training and introduction of improved
      workflow management systems, e.g. the central case management. CONCLUSION: The
      need for surgeons with advanced skills in business, finance and organisational
      management is evident and will require systematic and tailored training.

PMID- 16572329
TI  - Video-assisted thyroidectomy: indications and results.
AB  - BACKGROUND AND AIMS: Minimally invasive video-assisted thyroidectomy (MIVAT) was
      set up and introduced in our department in 1998. Its results, after an acceptable
      relapse, can now be evaluated, also speculating on new possible indications.
      PATIENTS AND METHODS: The procedure is based on a unique incision in the central
      neck, 2 cm above the sternal notch, using small conventional retractors and
      needlescopic (2 mm) reusable instruments. Haemostasis is achieved by a harmonic
      scalpel. Patients, 833, underwent MIVAT since June 1998. There were 715 females
      and 118 males (ratio 4:1). Lobectomy was carried out in 323 (38.7%) patients,
      total thyroidectomy in 510 (61.2%) patients. RESULTS: Mean operative time of
      lobectomy was 36.2 min (range: 20-120); for total thyroidectomy, 46.1 min (30
      130). Conversion to standard cervicotomy was required in 16 cases (1.9%);
      Operative complications were represented by transient monolateral recurrent nerve
      palsy in eight cases (0.9%), definitive monolateral recurrent nerve palsy in
      seven cases (0.8%). Twenty patients exhibited a hypoparathyroidism, which
      corresponds to 3.9% of total thyroidectomies performed, but only two showed
      permanent hypoparathyroidism (0.3%). CONCLUSION: MIVAT can be considered a safe
      operation offering significant cosmetic advantages with possible new promising
      indications such as prophylactic thyroidectomy in rearranged during transfection
      (RET) gene mutation carriers. It is still limited to a minority of patients, in
      particular, in endemic goitre countries.

PMID- 16572330
TI  - Effect of water-soluble reduced chitosan on Streptococcus mutans, plaque regrowth
      and biofilm vitality.
AB  - The purpose of the present study was to examine the effects of a newly developed
      water-soluble reduced chitosan on Streptococcus mutans, plaque regrowth, and
      biofilm vitality. A 1.0%, water-soluble reduced chitosan, with pH ranging from
      6.0 to 6.5, molecular weights between 3,000 and 5,000 Da, and 70% degree of
      deacetylation, was used. To determine antibacterial and antiplaque potency of
      chitosan, minimal inhibitory concentrations (MICs) for S. mutans and S. sanguinis
      (formerly S. sanguis), short-term exposure to S. mutans, and clinical trial of
      plaque regrowth and biofilm vitality were conducted. Twelve dental students
      volunteered to participate in the 6-week, double blind, randomized clinical trial
      using the classical 4-day plaque regrowth design. The MIC of water-soluble
      reduced chitosan for S. mutans was 1.25 g/l. While the cells exposed to distilled
      water (DW) grew rapidly, with a maximum turbidity reached by 16 h
      postinoculation, S. mutans exposed to chitosan (5.0 g/l) exhibited a substantial
      delay in growth and reached a maximum turbidity by 32 h postinoculation. The
      chitosan solution reduced the plaque index and the vitality of the plaque flora
      significantly when compared to DW, but this was less than the reductions found
      with the positive control of 0.1% chlorhexidine solution. The water-soluble
      reduced chitosan exhibited potent antibacterial effect on S. mutans, and
      displayed a significant antibacterial and plaque-reducing action during the 4-day
      plaque regrowth.

PMID- 16572331
TI  - Neuromuscular recovery after a strength training session in elderly people.
AB  - Ageing is associated with an increased susceptibility to muscle damage but little
      is known on how this affects muscle recovery after exercise. Hence, this study is
      aiming at investigating the effects of a heavy-resistance training session of
      neuromuscular recovery of the calf muscles of a group of elderly men aged >65.
      Maximal isometric and isokinetic torque, muscle voluntary activation (VA)
      capacity, surface electromyographic activity (EMG), peak-to-peak amplitude of
      action potentials associated with twitch responses of plantar flexors were
      evaluated before and 5 min (post1), 24 h (post2) and 48 h (post3) after 10 sets
      of 10 repetitions of a calf raise exercise performed at an intensity of 70% of
      the individual, one repetition maximum. Blood samples were taken before and 1,
      48, 96 and 144 h after the training session and assayed for serum creatine kinase
      (CK), lactate dehydrogenase (LDH) and myoglobin (Mb). Peak torque during
      eccentric and concentric (120 degrees s-1) contractions and twitch parameters
      were significantly reduced at post1, and recovered completely at post2. No
      significant changes were found in integrated EMG, M-wave amplitudes and VA
      throughout the entire test period. CK and LDH concentrations reached peak values
      48 h after the exercise session and returned to the pre-exercise values 96 h
      after the training session. Serum Mb level increased by 73.2% 1 h after exercise
      and recovered at 48 h. The reduction in peak torque following a strength training
      session in an elderly population could be explained mainly by fatigue of
      peripheral origin. After 24 h the elders recovered completely their capacities of
      strength production, despite muscle damage being still evident 48 h after the
      strength training session.

PMID- 16572332
TI  - Catheter-based intraluminal optical coherence tomography (OCT) of the ureter: ex
      vivo correlation with histology in porcine specimens.
AB  - Intraluminal optical coherence tomography (OCT) applies coherent light to provide
      cross-sectional images with a spatial resolution of 10-25 microm. We compared OCT
      and matching whole-mount histology microscopy sections of porcine upper ureters
      ex vivo for visualization and delineation of different tissue layers of the
      ureteral wall. Porcine ureters (six specimens, 24 quadrants) were flushed with
      normal saline solution prior to insertion of the OCT catheter (diameter, 0.014
      inch, OCT wavelength, 1,300+/-20 nm). Cross-sectional OCT images were obtained in
      marked locations before specimens were fixed in 4% formalin, cut at marked
      locations, whole-mounted, and stained with hematoxilin and eosin. Visualization
      and delineation of different tissue layers of the ureteral wall by OCT was
      compared with matching histology by two independent observers (O1,O2). OCT
      distinguished tissue layers of the ureteral wall in all quadrants. In OCT images,
      O1/O2 delineated urothelium and lamina propria in 23/24 quadrants, lamina propria
      and muscle layer in 19/16 quadrants, inner and outer muscle layer in 13/0
      quadrants, and urothelial cell layers in 13/2 quadrants, respectively.
      Intraluminal OCT provides histology-like images of the ureter in porcine
      specimens ex vivo and reliably distinguishes between urothelium and deeper tissue
      layers of the ureteral wall.

PMID- 16572335
TI  - Precolostral serology in calves born from Neospora-seropositive mothers.
AB  - The present study was designed to exploratively determine (a) how many healthy
      calves, born from seropositive mothers, were also precolostrally seropositive;
      (b) how many precolostrally negative calves became postcolostrally positive; and
      (c) in these calves, how the IgG1/IgG2 situation developed pre- and
      postcolostrally. All calves were born from mothers that were determined to be
      seropositive in a conventional Neospora caninum-ELISA and by immunoblotting. When
      the diagnostic performance of the conventional ELISA was compared with that of
      immunoblotting and an IgG1/IgG2-ELISA in the calves, the latter two exhibited a
      higher sensitivity: From a total of 15 precolostral calf sera, 7 were positive in
      the conventional ELISA (diagnostic sensitivity 47%) compared to 15 that were
      positive by immunoblotting (diagnostic sensitivity 100%) and 12 that were
      positive by the IgG1/IgG2-ELISA (diagnostic sensitivity 80%). With regard to
      IgG1/IgG2 findings in the dams, IgG2 appeared as the dominant subclass in the
      humoral immune response of adult cattle, while in calves, IgG1 appeared as the
      main prenatally/precolostrally reactive antibody isotype. Provided that
      precolostral seropositivity reflects postnatal persistent infection with N.
      caninum, we then postulate that, basically, all of our study calves born form N.
      caninum-seropositive mothers were prenatally infected with the parasite, and may,
      thus, all become members of the next transmitting generation.

PMID- 16572334
TI  - Role of magnetic resonance imaging in entrapment and compressive neuropathy -
      what, where, and how to see the peripheral nerves on the musculoskeletal magnetic
      resonance image: part 1. Overview and lower extremity.
AB  - The diagnosis of nerve entrapment and compressive neuropathy has been
      traditionally based on the clinical and electrodiagnostic examinations. As a
      result of improvements in the magnetic resonance (MR) imaging modality, it plays
      not only a fundamental role in the detection of space-occupying lesions but also
      a compensatory role in clinically and electrodiagnostically inconclusive cases.
      Although ultrasound has undergone further development in the past decades and
      shows high resolution capabilities, it has inherent limitations due to its
      operator dependency. We review the general concepts that should be known to
      evaluate the entrapment and compressive neuropathy in MR imaging. We also review
      the course of normal peripheral nerves, as well as various clinical
      demonstrations and pathological features of compressed and entrapped nerves in
      the lower extremities on MR imaging, according to the nerves involved. The common
      sites of nerve entrapment of the lower extremity are as follows: sciatic nerve
      around the piriformis muscle; tibial nerve at the popliteal fossa and tarsal
      tunnel, common peroneal nerve around the fibular neck, and digital nerve near the
      metatarsal head. Although MR imaging can depict the peripheral nerves in the
      extremities effectively, radiologists should be familiar with nerve pathways,
      common sites of nerve compression, and common space-occupying lesions resulting
      in nerve compression in MR imaging.

PMID- 16572336
TI  - Serological, intradermal and live flea challenge tests in the assessment of
      hypersensitivity to flea antigens in cats (Felis domesticus).
AB  - The results of intradermal testing with three commercial flea antigens and a
      serological test for IgE antibodies to flea antigens were compared with live flea
      challenge in cats. Eight control cats with no prior flea exposure had negative
      serological test and flea challenge results. By contrast, 17 out of 27 cats with
      previous flea exposure showed immediate reactivity to flea challenge; reactivity
      at 6, 24 and 48 h after flea exposure was noted in 12, 16 and 21 cats,
      respectively. Seventeen of these cats had positive serological test results.
      Seven cats showed immediate intradermal test reactions to the ARTU allergen, six
      reacted to the Biophady allergen, and six reacted to the Greer allergen.
      Intradermal test reactivity was less frequent at the other time points. Using the
      results of the flea challenge as the 'gold standard' for the presence or absence
      of sensitisation to fleas, the sensitivity and specificity of the serological
      test was 0.88 and 0.77, respectively. Sensitivities of the intradermal tests at
      the four time points ranged from 0 to 0.33, whereas the specificities ranged from
      0.78 to 1.0. Live flea challenge is better able to detect cats with
      hypersensitivity to fleas than either intradermal or serological testing.

PMID- 16572333
TI  - Role of magnetic resonance imaging in entrapment and compressive neuropathy-
      what, where, and how to see the peripheral nerves on the musculoskeletal magnetic
      resonance image: part 2. Upper extremity.
AB  - The diagnosis of nerve entrapment and compressive neuropathy has been
      traditionally based on the clinical and electrodiagnostic examinations. As a
      result of improvements in the magnetic resonance (MR) imaging modality, it plays
      not only a fundamental role in the detection of space-occupying lesions, but also
      a compensatory role in clinically and electrodiagnostically inconclusive cases.
      Although ultrasound has undergone further development in the past decades and
      shows high resolution capabilities, it has inherent limitations due to its
      operator dependency. We review the course of normal peripheral nerves, as well as
      various clinical demonstrations and pathological features of compressed and
      entrapped nerves in the upper extremities on MR imaging, according to the nerves
      involved. The common sites of nerve entrapment of the upper extremity are as
      follows: the brachial plexus of the thoracic outlet; axillary nerve of the
      quadrilateral space; radial nerve of the radial tunnel; ulnar nerve of the
      cubital tunnel and Guyon's canal; median nerve of the pronator syndrome, anterior
      interosseous nerve syndrome, and carpal tunnel syndrome. Although MR imaging can
      depict the peripheral nerves in the extremities effectively, radiologists should
      be familiar with nerve pathways, common sites of nerve compression, and common
      space-occupying lesions resulting in nerve compression in MR imaging.

PMID- 16572338
TI  - Systematic comparison of two methods to measure parasite density from malaria
      blood smears.
AB  - This study was designed to directly compare the accuracy, reproducibility, and
      efficiency of three methods commonly used to measure blood-stage malaria parasite
      density from Giemsa-stained blood films. Parasites and white blood cells (WBCs)
      were counted in 154 thick films by two independent microscopists. Forty-six
      slides were read by counting parasitized red blood cells (RBCs) in the thin film.
      Using these same slides, parasites were again counted by two independent
      microscopists using an ocular grid. Overall, parasite densities were
      significantly lower and discrepancy between readers was higher when using the
      grid method compared to the WBC method, but there was no difference when compared
      to the RBC method. When one reader who had difficulty with the grid method was
      excluded, the discrepancy between readers was equivalent for the three methods.
      Densities and discrepancy between readers were indistinguishable when parasites
      were counted until 200 or 500 WBCs. Counting beyond 200 WBCs may not
      significantly improve parasite density measurements. Using an ocular grid
      directly measures parasites per volume rather than using a WBC per microliter
      conversion factor and eliminates the need to switch from the thick film to the
      thin film for high parasitemias. However, significant differences in densities
      measured by the grid method and the WBC method need to be evaluated.

PMID- 16572340
TI  - Cystinuria presenting with acute renal failure and hyperkalemia.

PMID- 16572337
TI  - Colonization of Aedes aegypti midgut by the endosymbiont-bearing trypanosomatid
      Blastocrithidia culicis.
AB  - Monoxenous trypanosomatids inhabit invertebrate hosts throughout their life
      cycle. However, there have been cases of HIV-positive patients who have presented
      opportunistic infections caused by these protozoa, offering new perspectives to
      the study of interactions between monoxenics and hematophagous insect vectors.
      Some monoxenous trypanosomatids present a symbiotic bacterium in the cytoplasm,
      which seems to promote biochemical and morphological changes in the host
      trypanosomatids, such as alterations in plasma membrane carbohydrates and the
      reduction of the paraxial rod. In this work, we investigated the colonization of
      Aedes aegypti with Blastocrithidia culicis, an endosymbiont-bearing
      trypanosomatid. B. culicis remained in the insect digestive tract for 38 days
      after feeding. Optical microscopy analysis revealed an infection process
      characterized by a homogenous distribution of the trypanosomatid along the midgut
      epithelium; no preferential interaction of protozoa with any cell type was
      observed. Ultrastructural analysis showed that during the colonization process,
      trypanosomatids interacted mainly with midgut cells through their flagellum,
      which penetrates the microvilli preferentially near the tight junctions.
      Prolonged infections promoted insect midgut degradation, culminating with the
      arrival of protozoa in the hemocel. By demonstrating B. culicis colonization in a
      bloodsucking insect, we suggest that vector transmission of monoxenous
      trypanosomatids to vertebrate host may occur in nature.

PMID- 16572339
TI  - Age-related pathophysiological changes in rat oligomeganephronic hypoplastic
      kidney.
AB  - Rat male hypogonadism (hgn/hgn) is accompanied by oligomeganephronic hypoplastic
      kidney (HPK), in which each kidney contains one quarter the number of nephrons
      present in a normal kidney. The nephrons of the HPK are extremely hypertrophied.
      These characters were apparently common to human oligomeganephronia (OMN). To
      determine the age-related changes in renal pathophysiology in HPK rats, we
      measured several parameters of renal function at 70 days, 140 days, 210 days, and
      280 days of age. At all time points, relative kidney weight was significantly
      smaller in HPK rats than in their normal litter mates. In HPK rats, both polyuria
      and polydipsia became more severe with advancing age. Although creatinine
      clearance (Ccr) and urinary nitrogen clearance (Cun) were significantly lower in
      HPK than in normal rats, the values did not decrease with age. A severe form of
      glomerulosclerosis, as well as interstitial infiltration and cystic dilation of
      tubules with proteinaceous luminal casts, was observed in the inner cortex and
      medulla of HPK rats at advanced age. In these animals the surface glomeruli
      retained their functional architecture but were hypertrophied. Both mean blood
      pressure (MBP) and proteinuria became more elevated with age in HPK rats, and
      their urine samples included considerable amounts of high molecular weight
      protein. These results suggest that the HPK rat is a suitable model of human OMN.

PMID- 16572341
TI  - Assessment of serum cystatin C in children with congenital solitary kidney.
AB  - The aim of the study was to assess serum cystatin C level in children with a
      congenital solitary kidney, depending on their age and compensatory overgrowth of
      the kidney. The study group (I) consisted of 36 children, 3-21 years of age
      (median 10.8 years), with a congenital solitary kidney and no other urinary
      defects. The control group (C) contained 36 healthy children, 5-21 years old
      (median 10.9 years). Nephelometric methods were used to determine serum cystatin
      C level, the Jaffe method to assess creatinine concentration and the Schwartz
      formula to estimate glomerular filtration rate. Kidney length was measured with
      the patient in a supine position, and overgrowth was estimated (O%) in comparison
      with the respective kidney in the control group. Serum cystatin C level in group
      I was higher than that in the control group (P<0.05). Increased values, above
      0.95 mg/l, were found in 16/36 (44%) children aged 12-21 years. Glomerular
      filtration rate (GFR, estimated by the Schwartz formula) and creatinine level in
      group I were similar to those of the control group (P>0.05). Increased kidney
      length was found (median 18.2%). Cystatin C concentration was positively
      correlated with O% (r=0.406, P<0.01) and kidney length to child height ratio
      (L/H) (r=0.376, P<0.05). We conclude that Increased serum cystatin C
      concentration in patients with a unilateral congenital solitary kidney occurs
      after 12 years of age and correlates with compensatory overgrowth of the kidney.

PMID- 16572342
TI  - Teaching molecular genetics: Chapter 3--Proteomics in nephrology.
AB  - The novel discipline of proteomics has experienced a rapid growth in the recent
      past and has great potentials for the future. The study of proteins on a genomic
      scale enables a large number of proteins to be analysed simultaneously. Moreover,
      proteomic analysis reveals the presence of protein isoforms and post
      translational modifications, both of which have the potential to regulate protein
      complex formation, activity and function. As such, the assessment of the
      proteome, unlike genomic analysis, provides a view of biological processes at
      their level of occurrence. The knowledge thus gained is important not only for a
      better understanding of renal physiology and pathophysiology, but also for the
      identification of disease markers and the development of new therapies. This
      review applies the science of proteomics to nephrology: our aim is to give an
      overview of the discipline, providing background information and outlining the
      scope, advantages and limitations of proteomics.

PMID- 16572344
TI  - Surgical planning of total hip arthroplasty: accuracy of computer-assisted
      EndoMap software in predicting component size.
AB  - PURPOSE: The purpose of our study was to assess the accuracy of a computer
      assisted templating in the surgical planning of patients undergoing total hip
      arthroplasty utilizing EndoMap software (Siemans AG, Medical Solutions, Erlangen,
      Germany). Endomap Software is an electronic program that uses DICOM images to
      analyze standard anteroposterior radiographs for determination of optimal
      prosthesis component size. METHODS: We retrospectively reviewed the preoperative
      radiographs of 36 patients undergoing uncomplicated primary total hip
      arthroplasty, utilizing EndoMap software, Version VA20. DICOM anteroposterior
      radiographs were analyzed using standard manufacturer supplied electronic
      templates to determine acetabular and femoral component sizes. No additional
      clinical information was reviewed. Acetabular and femoral component sizes were
      assessed by an orthopedic surgeon and two radiologists. Mean and estimated
      component size was compared with component size as documented in operative
      reports. RESULTS: The mean estimated acetabular component size was 53 mm (range
      48-60 mm), 1 mm larger than the mean implanted size of 52 mm (range 48-62 mm).
      Thirty-one of 36 acetabular component sizes (86%) were accurate within one size.
      The mean calculated femoral component size was 4 (range 2-7), 1 size smaller than
      the actual mean component size of 5 (range 2-9). Twenty-six of 36 femoral
      component sizes (72%) were accurate within one size, and accurate within two
      sizes in all but four cases (94%). CONCLUSION: EndoMap Software predicted femoral
      component size well, with 72% within one component size of that used, and 94%
      within two sizes. Acetabular component size was predicted slightly better with
      86% within one component size and 94% within two component sizes.

PMID- 16572345
TI  - New accessory for studies of isotopic 1H/2H exchange and biomolecular
      interactions using transmission infrared spectroscopy.
AB  - We present here a new accessory for IR transmission measurements of 1H/2H
      exchange, as an ancillary tool for monitoring structural features of biomolecules
      in aqueous solution. This new accessory results from the combination of two
      dialysis membranes and a conventional liquid cell having two cylinders containing
      2H2O buffer. When compared with conventional transmission measurements, carried
      out either after dissolving lyophilized biomolecules in 2H2O or after dialyzing
      the aqueous solution considered against 2H2O buffer, this accessory shows the
      following advantages: (1) controlled measurements over the initial steps of this
      isotopic exchange and absence of molecular aggregation, and (2) smaller sample
      amounts. This new Fourier transform IR cell can also be used to analyze ligand
      biomolecule and drug-cell interactions.

PMID- 16572343
TI  - Mutation G47R in the BSND gene causes Bartter syndrome with deafness in two
      Spanish families.
AB  - Bartter syndrome (BS) is a heterogeneous group of autosomal recessive
      hypokalaemic salt-losing tubulopathies. Five types of BS caused by different
      genetic defects have been identified, and one of them is associated with
      sensorineural deafness (BSND). Mutations in the recently described BSND gene,
      mapped in chromosome 1p31, have been reported to be associated with BSND. This
      gene encodes barttin, an essential beta-subunit subunit for ClC-Ka and ClC-Kb
      channels. Both subunits are co-expressed in basolateral membranes of renal
      tubules, in the ascending limb of the loop of Henle, and in the stria vascularis
      of the inner ear. We studied two apparently unrelated Spanish families from the
      Canary Islands, with five members showing this pathology. Sequence analysis of
      the BSND gene showed that the affected members were homozygous for a C-to-T
      transition in exon 1, while their parents were heterozygous. This alteration
      results in a missense mutation, G47R, which has been previously shown to abolish
      the stimulatory effect on the subunit barttin of the ClC-Kb channel. Our results
      indicate that families with the G47R mutation indeed present polyhydramnios,
      premature birth and salt loss. Nevertheless, glomerular filtration rate was
      normal in all patients. Clinical manifestations are moderate in patients with the
      G47R mutation compared to other published data form patients with BSND. This
      constitutes the first report of BSND cases in Spain.

PMID- 16572346
TI  - Engineered Bacillus thuringiensis GO33A with broad insecticidal activity against
      lepidopteran and coleopteran pests.
AB  - A recombinant plasmid pSTK-3A containing cry3Aa7 gene encoding a coleopteran
      specific insecticidal protein was constructed and introduced into wild Bacillus
      thuringiensis subsp. aizawai G03, which contained cry1Aa, cry1Ac, cry1Ca, and
      cry2Ab genes and was highly toxic to lepidopteran insect pests. The genetically
      engineered strain were named G033A. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and Western blot analysis demonstrated that the cry3Aa7 gene was
      expressed normally and produced a 67 kDa protein in G033A, and the flat
      rectangular crystals of Cry3Aa7 toxin protein was observed under scanning
      electron microscope. The recombinant plasmid was maintained in bacteria cultured
      for 180 generations in culture media containing no antibiotics. Synthesis of the
      Cry3Aa7 toxin conferred high and broad toxicity to the recombinant strain G033A
      against coleopteran order, elm leaf beetle (Pyrrhalta aenescens) (LC(50) 0.35
      mg/ml), for which the parental strain G03 was not toxic. Both the parental strain
      G03 and recombinant strain G033A showed strong insecticidal activity to
      lepidopteran pests, beet armyworm (Spodoptera exigua), diamondback moth (Plutella
      xylostella), and cotton bollworm (Helicoverpa amigera), respectively. The lethal
      concentration 50% (LC(50)) of G033A against S. exigua, P. xylostella, and H.
      amigera was 4.26, 0.86, and 1.76 microg/ml, respectively.

PMID- 16572347
TI  - Esophageal squamous cell carcinoma with entirely intramural growth pattern.
AB  - Esophageal cancers are predominantly carcinomas, which are-due to their origin
      from the epithelial lining-visible by endoluminal view. We report in this study
      about the rare case of an esophageal squamous cell cancer with an unusual,
      entirely intramural growth pattern. The diagnosis could only be established
      postoperatively, because all preoperative biopsies had failed to demonstrate the
      tumor. The entirely intramural growth pattern of esophageal squamous cell cancer
      is an exceedingly rare variant, with only one previously reported case.
      Nevertheless, clinicians, radiologists, and pathologists should be aware of the
      potential existence of this condition, especially when clinical and imaging
      results suggest a malignant tumor that cannot be proven on biopsies. Surgical
      exploration must be considered under these circumstances.

PMID- 16572348
TI  - Tissue-specific transcription profiles of sex steroid biosynthesis enzymes and
      the androgen receptor.
AB  - 17beta-hydroxysteroid dehydrogenase (17beta-HSD) and 5alpha-reductase isoenzymes
      play a crucial role in the formation and metabolism of sex steroids. Not only the
      key androgens testosterone and dihydrotestosterone but also their precursors are
      potent activators of the androgen receptor and are, therefore, likely to act as
      determinants of male sexual differentiation and maturation in a differentially
      regulated way. The aim of the present study was to relatively quantify the
      expression of the mRNA of 17beta-HSD isoenzymes, namely, type 1, 2, 3, 4, 5, 7,
      and 10, together with the 5alpha-reductase type 1 and 2, and the androgen
      receptor in normal human males and females. RNA was isolated from peripheral
      blood cells of both sexes and from genital skin fibroblasts (GSFs) of two
      different localizations (foreskin and scrotal skin) obtained from phenotypically
      normal males. mRNA expression was semi-quantified by quantitative reverse
      transcriptase polymerase chain reaction with the LightCycler Instrument (Roche).
      The examined enzymes show statistically significant differences in their
      transcription pattern between the blood and the GSF RNA samples. Within the GSF
      samples, there are also significant variations between the two examined
      localizations in the transcription of 17beta-HSD type 1, 2, 4, and 5 as well as
      for the androgen receptor. We found large interindividual variation of enzyme
      transcription patterns in all investigated tissues. In peripheral blood cells, no
      sex-specific differences were seen. We conclude that sex steroid enzymes are
      expressed not only in genital primary target tissues but also in peripheral
      blood. The expression in different target tissues may contribute to both the
      individual sexual and tissue-specific phenotype in humans.

PMID- 16572349
TI  - Myoepithelial hamartoma causing small-bowel intussusception: a case report and
      literature review.
AB  - We report an unusual case of a 5-month-old girl who suffered an ileo-ileal
      intussusception that was not reduced by hydrostatic reduction. Surgical treatment
      revealed that the leading point was a tumor 1.5 cm in diameter. Myoepithelial
      hamartoma was diagnosed histopathologically. The literature indicates that MEH
      rarely causes small-bowel intussusception in childhood.

PMID- 16572350
TI  - Autonomic dysfunction and impaired cerebral autoregulation in cirrhosis.
AB  - Cerebral blood flow autoregulation is lost in patients with severe liver
      cirrhosis. The cause of this is unknown. We determined whether autonomic
      dysfunction was related to impaired cerebral autoregulation in patients with
      cirrhosis. Fourteen patients with liver cirrhosis and 11 healthy volunteers were
      recruited. Autonomic function was assessed in response to deep breathing, head-up
      tilt and during 24-h Holter monitoring. Cerebral autoregulation was assessed by
      determining the change in mean cerebral blood flow velocity (MCAVm, transcranial
      Doppler) during an increase in blood pressure induced by norepinephrine infusion
      (NE). The severity of liver disease was assessed using the Child-Pugh scale
      (class A, mild; class B, moderate; class C, severe liver dysfunction).NE
      increased blood pressure similarly in the controls (27 (24-32) mmHg) and patients
      with the most severe liver cirrhosis (Child-Pugh C, 31 (26-44) mmHg, p=0.405 Mann
      Whitney). However, the increase in MCAVm was greater in cirrhosis patients
      compared to the controls (Child-Pugh C, 26 (24-39) %; controls, 3 (-1.3 to 3) %;
      respectively, p=0.016, Mann-Whitney). HRV during deep breathing was reduced in
      the cirrhosis patients (Child-Pugh C, 6.0+/-2.0 bpm) compared to the controls
      (21.7+/-2.2 bpm, p=0.001, Tukey' test). Systolic blood pressure fell during head
      up tilt only in patients with severe cirrhosis. Our results imply that cerebral
      autoregulation was impaired in the most severe cases of liver cirrhosis, and that
      those with impaired cerebral autoregulation also had severe parasympathetic and
      sympathetic autonomic dysfunction. Furthermore, the degree of liver dysfunction
      was associated with increasing severity of autonomic dysfunction. Although this
      association is not necessarily causal, we postulate that the loss of sympathetic
      innervation to the cerebral resistance vessels may contribute to the impairment
      of cerebral autoregulation in patients with end-stage liver disease.

PMID- 16572351
TI  - Acetylcholinesterase inhibition and orthostatic hypotension.

PMID- 16572353
TI  - [Retinopathy of prematurity].

PMID- 16572352
TI  - Oligonucleotide-polyethylenimine complexes targeting retinal cells: structural
      analysis and application to anti-TGFbeta-2 therapy.
AB  - PURPOSE: The aim of this study was to characterize oligonucleotide
      polyethylenimine (ODN/PEI) complex preparation for potential transfection of
      retinal cells in vitro and in vivo. METHODS: The effect of medium preparation
      [HEPES-buffered saline (HBS), water] on particle size and morphology was
      evaluated. Cultured Lewis rat retinal Muller glial (RMG) cells were transfected
      using fluorescein isothiocyanate (FITC)-ODN/PEI complexes specifically directed
      at transforming growth factor beta (TGFbeta)-2. Efficacy of transfection was
      evaluated using confocal microscopy, and regulation of gene expression was
      assayed using quantitative real-time RT-PCR and ELISA assay. One, 24, and 72 h
      after injection of FITC-ODN/PEI complexes into the vitreous of rat eyes, their
      distribution was analyzed on eye sections. RESULTS: Complexes prepared in HBS
      were smaller than complexes prepared in pure water and presented a core-shell
      structure. These particles showed a high cellular internalization efficacy, along
      with a significant and specific down-regulation of TGFbeta-2 expression and
      production in RMG cells, correlating with specific inhibition of cell growth at
      72 h. In vivo, complexes efficiently transfect retinal cells and follow a
      transretinal migration at 24 h. After 72 h, ODN seems to preferentially target
      RMG cells without inducing any detectable toxicity. CONCLUSIONS: Specific down
      regulation of TGFbeta-2 expression using ODN/PEI complexes may have potential
      interest for the treatment of retinal diseases associated with glial
      proliferation.

PMID- 16572355
TI  - [Independent Clinic Research: it's possible].

PMID- 16572354
TI  - [The hazy frontier between fraud and scientific truth].

PMID- 16572356
TI  - [Sector-based analysis of the distribution of the neuroretinal rim by confocal
      scanning laser in the diagnosis of glaucoma].
AB  - PURPOSE: To evaluate the diagnostic ability of the Moorfields regression analysis
      (MRA; neuroretinal rim sector-based analysis) by means of confocal scanning
      laser. METHODS: 200 eyes were included in this study: 101 normal subjects and 99
      glaucoma patients (standard automated perimetry with glaucomatous defects -MD or
      CPSD with p<0.02 or a cluster of three or more points with p<0.05 or a cluster of
      two or more points with p<0.01 or abnormal Glaucoma Hemifield Test). All subjects
      underwent a full ophthalmic evaluation, visual field evaluation by means of a
      Humphrey Field Analyzer, 24-2 full threshold strategy, and optic disc topography
      by Heidelberg retina tomograph (HRT-II). The outcome parameters were sensitivity
      and specificity of the MRA for each sector. RESULTS: The highest sensitivity in
      detecting structural defects based on MRA (p<0.05) was observed in the nasal
      superior sector (48%) and nasal-inferior sector (45%); however the highest
      specificity was found in the temporal-superior (98%) and inferior (98%) sectors.
      The highest sensitivity for MRA (p<0.01) was found in the temporal-inferior
      sector (31%) and nasal-superior sector (30%) while the temporal-superior and
      inferior-sectors showed the highest specificity (100%). The diagnosis of glaucoma
      based on the presence of any sector alteration showed sensitivity figures of 67%
      with p<0.05 and 46% with p<0.01 and specificity values of 84% with p<0.05 and 96%
      with p<0.01. CONCLUSIONS: The analysis of the distribution of the neuroretinal
      rim by means of HRT-II contributes effectively to the diagnosis of glaucoma based
      on perimetry in a sample derived from a Spanish population.

PMID- 16572357
TI  - [Diplopia after sub-Tenon's anesthesia for cataract surgery].
AB  - PURPOSE: To study the clinical signs, treatment and prognosis of strabismus after
      sub-Tenon's anesthesia for cataract surgery. METHODS: Eight patients without
      previous strabismus developed incomitant diplopia immediately after cataract
      surgery; the left eye was affected in five patients and the right eye in three.
      Restrictive strabismus was diagnosed with the cover test, prisms, and active and
      passive ductions in all cases. In seven cases the deviation was vertical and in
      one patient it was horizontal. The average deviation was 17.5 S.D. 9.84 (range 5
      35) prismatic dioptres in primary position. The deviation increased looking
      upward in seven cases, and looking sideways to the left in the other. It was
      considered to be a good result if the diplopia disappeared after treatment.
      RESULTS: Botulinum toxin was the first treatment applied in four patients, but
      only one showed a good response and required no further therapy. Strabismus
      surgery was required in four cases, and prisms were adapted in three. Three
      patients required two strabismus operations. A good result was achieved in all
      cases, with the average time interval being 10.12 (SD 5.5) months. CONCLUSIONS:
      Sub-Tenon's anesthesia may result in restrictive strabismus and incomitant
      diplopia which does not resolve spontaneously. The inferior rectus is the most
      commonly affected muscle. Strabismus surgery is required to resolve the diplopia
      in half of the cases. Good results have been achieved in all patients.

PMID- 16572359
TI  - [Ocular hypertension in children treated with brimonidine 0.2%. A clinical
      study].
AB  - PURPOSE: To evaluate the safety and efficacy of topical brimonidine 0.2% use in
      children. MATERIALS AND METHODS: A descriptive study of twelve successive
      children (21 eyes) who needed topical treatment of intraocular hypertension, and
      where the use of b-blockers was contraindicated. RESULTS: During treatment we
      observed an average decrease of IOP of 5 SD 1.8 mmHg (21% of basal IOP), but
      found more common local symptoms, with stinging being complained of in 52.4% of
      cases. Somnolence was also complained of in two cases.

PMID- 16572358
TI  - [Pseudophakic cystoid macular edema. Assessment with optical coherence
      tomography].
AB  - PURPOSE: To determine the incidence of cystoid macular edema (CME) by means of
      clinical evaluation and subclinical assessment by means of ocular coherence
      tomography (OCT), and to compare the incidence between diabetic and non-diabetic
      groups of patients. METHODS: Prospective study of 260 consecutive cataract
      surgeries operated from September 2004 to March 2005. The procedures were
      performed by means of phacoemulsification plus intraocular acrylic lens
      implantation. Group A: 208 eyes of non-diabetic patients; Group B: 42 eyes of
      patients with diabetes and Group C: 10 eyes of diabetic patients with macular
      edema that received an intravitreal injection of triamcinolone at the end of
      surgery. Postoperative follow-up visits were performed 6 days (basal visit), 5
      weeks and 12 weeks after surgery. Each visit included posterior pole
      biomicroscopy and OCT. RESULTS: Central macular thickness measured by OCT was
      significantly increased in group B compared with group A (241.6 versus 204.6
      microm; p<0.001). No clinical evidence of CME was found in group A, although 4
      eyes (1.92%) showed macular thickness equal to or greater than 43.74 microm (2
      standard deviations of the basal value for group A). In group B, clinical
      evidence of CME was found in 6 eyes, with decreased visual acuities (14.2%). The
      differences between these groups were statistically significant (p<0.001). The 10
      eyes that received an intravitreal injection of triamcinolone after the surgical
      procedure showed a mean decrease in central retinal thickness of 77 microm after
      12 weeks postoperative. CONCLUSIONS: This study has shown a low incidence of
      clinical CME. OCT showed increased macular thickness in both groups of patients
      in a small percentage of cases, and significantly increased macular thickness in
      diabetic patients.

PMID- 16572360
TI  - [Acute pancreatitis presenting as sudden blindness].
AB  - CASE REPORT: A 36-year-old man with a history of alcohol abuse presented with
      sudden blindness. The ophthalmologic examination showed Purtscher-like
      retinopathy. The presumed diagnosis was acute pancreatitis, which was confirmed
      by complementary laboratory studies. DISCUSSION: Sudden acute visual loss with
      Purstcher-like retinopathy may be present in acute pancreatitis, although it is a
      very rare as a presenting symptom. Early diagnosis based on ophthalmic symptoms
      may help in the recognition and treatment of the disease and prevent later
      complications.

PMID- 16572361
TI  - [Photic maculopathy and iris damage in a psychotic patient].
AB  - CASE REPORT: A 37-year-old psychotic patient inflicted injuries to his skin and
      eyes in the context of an interpretational delirium with aesthetic content. He
      used magnifying glasses to concentrate sunlight and suffered burns to his arms
      and face. In the eyes, these resulted in massive iridial atrophy with loss of the
      sphincteric function, photic maculopathy and peripheral retinal coagulation. The
      macular lesion resolved spontaneously although he did not recover visual acuity.
      DISCUSSION: This is the first reported case of ocular self-injury secondary to
      sunlight. It is also the first case reporting retinal photo-coagulative lesions
      secondary to sunlight.

PMID- 16572362
TI  - [Visual symptoms as the first manifestation of Alzheimer's disease].
AB  - CASE REPORT: We report a 59-year-old patient with difficulty in visual
      perception, difficulty reading and episodes of dyschromatopsia. The ocular
      examination was unremarkable. Structural neuro-imaging and neuro-ophthalmology
      tests were normal. Positron emission tomography scanning showed decreased
      metabolism in the parieto-occipital cortex bilaterally. Several months later the
      patient developed Alzheimer's disease. DISCUSSION: Visual symptoms may be the
      first manifestation of Alzheimer's disease.

PMID- 16572363
TI  - [Eyelid tick bite].
AB  - CASE REPORT: We describe a patient who was bitten on his right upper eyelid by a
      common canine tick. The tick was impregnated with gasoline prior to being
      removed. DISCUSSION: Tick bites are uncommon in ophthalmologic practice. They
      occur more frequently in rural areas, especially in spring and summer. Correct
      identification of the problem and treatment is essential. The tick needs to be
      completely removed in order to avoid the embedding of different parts of the
      insect. Zoonoses, such as rickettsiosis, arbovirus and paralysis due to ticks
      must be ruled out.

PMID- 16572364
TI  - [A Century ago. Exceptional year. Important publications in "Archives". A medical
      student beat Barcelona].

PMID- 16572365
TI  - [Ophthalmology meeting in Palma de Mallorca, 1934].

PMID- 16572366
TI  - Gene doping.
AB  - Together with the rapidly increasing knowledge on genetic therapies as a
      promising new branch of regular medicine, the issue has arisen whether these
      techniques might be abused in the field of sports. Previous experiences have
      shown that drugs that are still in the experimental phases of research may find
      their way into the athletic world. Both the World Anti-Doping Agency (WADA) and
      the International Olympic Committee (IOC) have expressed concerns about this
      possibility. As a result, the method of gene doping has been included in the list
      of prohibited classes of substances and prohibited methods. This review addresses
      the possible ways in which knowledge gained in the field of genetic therapies may
      be misused in elite sports. Many genes are readily available which may
      potentially have an effect on athletic performance. The sporting world will
      eventually be faced with the phenomena of gene doping to improve athletic
      performance. A combination of developing detection methods based on gene arrays
      or proteomics and a clear education program on the associated risks seems to be
      the most promising preventive method to counteract the possible application of
      gene doping.

PMID- 16572367
TI  - Left atrial geometric and functional remodeling in athletes.
AB  - The aim of this study was to evaluate left atrial (LA) volume and its changes
      with the phases of atrial filling, and to examine the effect of exercise capacity
      on these parameters. Using two-dimensional echocardiography, LA volumes were
      measured in 30 male endurance runners and 30 age-matched sedentary men
      (controls). Maximal oxygen consumption (VO2max) was measured using a metabolic
      chart during exercise. LA reservoir, pump, and conduit functions, kinetic energy
      and force were calculated. We found that athletes had higher LA volume and volume
      index (except the conduit volume), LA passive emptying fraction, and LA total
      emptying fraction compared to control subjects. We observed positive correlations
      between: VO2max and LA passive emptying fraction (r=0.49, p<0.05); VO2max and LA
      active emptying fraction (r=0.54, p<0.05); VO2max and LA kinetic energy (r=0.61,
      p<0.05); and VO2max and LA force (r=0.57, p<0.05). These findings suggest that
      atrial function reflects exercise capacity in athletes.

PMID- 16572368
TI  - Plasma adiponectin response to sculling exercise at individual anaerobic
      threshold in college level male rowers.
AB  - The purpose of the investigation was to study plasma adiponectin response to a
      single exercise session in male rowers. Eight college level, single scull rowers
      (VO2max: 5.01+/-0.43 l.min-1; age: 21.5+/-4.5 yrs; height: 184.9+/-5.0 cm; body
      mass: 78.5+/-8.4 kg; body fat: 11.8+/-1.2%) participated in this study. Venous
      blood samples were obtained before, immediately after, and following the first 30
      min of recovery of constant load on-water rowing over a distance of 6.5 km
      (approximately 30 min) at the individual anaerobic threshold (75.2+/-2.9% of
      VO2max). Adiponectin was unchanged (p>0.05) immediately after the exercise.
      However, adiponectin was significantly increased above the resting value after
      the first 30 min of recovery (+14.7%; p<0.05). Similarly, leptin was unchanged
      immediately after exercise and was significantly decreased after the first 30 min
      of recovery (-18.2%; p<0.05). Plasma insulin was significantly reduced
      immediately after exercise and remained significantly lower during the first 30
      min of recovery period. Glucose increased with exercise and returned to the pre
      exercise level after the first 30 min of recovery. Basal adiponectin was
      significantly related to VO2max (r=-0.62; p=0.034). However, there was no
      relationship between basal adiponectin and other measured variables. Similarly,
      basal leptin demonstrated no relationship with other measured variables. In
      conclusion, the results of the present study suggest that plasma adiponectin is
      sensitive in the first 30 min of recovery to the effects of relatively short-term
      exercise at individual anaerobic threshold when all major muscle parts are
      involved.

PMID- 16572369
TI  - The relationship between the lactate turnpoint and the time at VO2max during a
      constant velocity run to exhaustion.
AB  - The present investigation examined the relationship between the running velocity
      at the lactate turnpoint (vLTP) and the time at which VO2max can be sustained
      (TVO2max) during a continuous run to exhaustion at the minimal running velocity
      that elicits VO2max (vVO2max). Seven moderately-trained endurance runners
      undertook three tests on a treadmill. The first test was to determine vVO2max;
      the second to determine the time to exhaustion during a constant velocity run at
      vVO2max (Tlim vVO2max) and TVO2max; and the third to determine the vLTP.
      Pearson's correlation coefficient was used to determine the association between
      the vLTP (%vVO2max; i.e. the relative vLTP) and TVO2max, and between other
      selected physiological variables. Correlations between the relative vLTP and
      TVO2max, expressed as a percentage of T(lim vVO2max (the relative TVO2max;
      r=0.82), and between TVO2max and Tlim vVO2max (r=0.89), were significant at the
      p<0.05 level. All other correlations between selected measured physiological
      variables were found to be statistically insignificant. The main finding of this
      present study is that the relative vLTP demonstrated a significant positive
      correlation with the relative TVO2max. The physiological mechanism by which the
      lactate turnpoint may influence the relative TVO2max has not been elucidated, but
      may be due to a combination of decreasing the time to attain VO2max and
      increasing Tlim vVO2max. The present investigation has demonstrated that the
      lactate turnpoint may influence the relative time at which VO2max can be
      sustained during a continuous run to exhaustion at vVO2max, although further
      research is required to substantiate these findings.

PMID- 16572370
TI  - Comparison of hematologic data in world elite junior speed skaters and in non
      athletic juniors.
AB  - During the world junior speed skating championship 2002 all athletes (60 males,
      56 females) were subjected to hematologic blood testing one day before the
      competition as requested by International Skating Union--ISU. This study aimed to
      obtain hematological reference values for junior athletes, whilst the influence
      of endurance training on hematologic variables of young athletes was studied.
      Hematologic results of athletes were compared to results of non-athletes matched
      by age and gender (14 males, 17 females). The blood analysis was done on an ADVIA
      120. To compare measurement of ferritin, erythropoietin, and soluble transferrin
      receptor in serum as well as in EDTA-plasma, serum and EDTA-blood was obtained
      from the control group. In hemoglobin and hematocrit we found no significant
      difference between the two groups, whereas the number of erythrocytes was lower
      in athletes. The mean corpuscular volume was higher in athletes, whilst the
      corpuscular hemoglobin content was only marginally higher in athletes than in non
      athletes. Consequently corpuscular hemoglobin concentration mean was lower in
      athletes than in non-athletes. There was no difference of erythropoietin and
      soluble transferrin receptor, whilst in ferritin we found a difference between
      the groups. Endurance training does not change the values of hemoglobin and
      hematocrit. Increased mean corpuscular volume and decreased corpuscular
      hemoglobin concentration mean could be a result of changed properties of red
      blood cell-membrane caused by acidosis and higher osmolality during the training.
      In junior athletes we did not find an iron overload as described in some adult
      athletes.

PMID- 16572371
TI  - Physiological measures associated with marathon running performance in high-level
      male and female homogeneous groups.
AB  - The study tested the hypothesis that physiological measurements can predict
      marathon running performance in a top-level homogeneous group of males and
      females. Ten male, performance: 2:12:04, coefficient of variation (CV)=2.33%, and
      8 female marathon runners, performance: 2:34:53, CV=4.54%, performed an increment
      test on the treadmill (starting speed, 8 km.h-1; increments, 2 km.h-1; increment
      duration, 3 min to exhaustion). The heart rate (HR), VO2 and the lactate
      concentrations were measured at the end of each exercise level. During the
      recovery time, HR and lactate were measured. Furthermore, echocardiographic,
      anthropometric and haematologic measurements were made. The results of a stepwise
      multiple regression analysis using marathon time as the dependent variable
      yielded R2=0.983 for the male group and R2=0.984 for the female group. The model
      for the male group used the independent variables lactate value at 10 km.h-1,
      left ventricular telediastolic diameter (LVD) and lactate value at 22 km.h-1. The
      model for the female group used the independent variables subscapular skinfold,
      serum ferritin and sum of six skinfolds. Our study demonstrates that in males and
      females, physiological parameters can explain the variance in marathon time among
      elite homogeneous groups.

PMID- 16572372
TI  - Effects of altering pedal cadence on cycling time-trial performance.

PMID- 16572373
TI  - Effect of acute hypoxia on maximal oxygen uptake and maximal performance during
      leg and upper-body exercise in Nordic combined skiers.
AB  - We examined the effect of normobaric hypoxia (3200 m) on maximal oxygen uptake
      (VO2max) and maximal power output (Pmax) during leg and upper-body exercise to
      identify functional and structural correlates of the variability in the decrement
      of VO2max (DeltaVO2max) and of maximal power output (DeltaPmax). Seven well
      trained male Nordic combined skiers performed incremental exercise tests to
      exhaustion on a cycle ergometer (leg exercise) and on a custom built doublepoling
      ergometer for cross-country skiing (upper-body exercise). Tests were carried out
      in normoxia (560 m) and normobaric hypoxia (3200 m); biopsies were taken from m.
      deltoideus. DeltaVO2max was not significantly different between leg (-9.1+/-4.9%)
      and upper-body exercise (-7.9+/-5.8%). By contrast, Pmax was significantly more
      reduced during leg exercise (-17.3+/-3.3%) than during upper-body exercise (
      9.6+/-6.4%, p<0.05). Correlation analysis did not reveal any significant
      relationship between leg and upper-body exercise neither for DeltaVO2max nor for
      DeltaPmax. Furthermore, no relationship was observed between individual
      DeltaVO2max and DeltaPmax. Analysis of structural data of m. deltoideus revealed
      a significant correlation between capillary density and DeltaPmax (R=-0.80,
      p=0.03), as well as between volume density of mitochondria and DeltaPmax (R=
      0.75, p=0.05). In conclusion, it seems that VO2max and Pmax are differently
      affected by hypoxia. The ability to tolerate hypoxia is a characteristic of the
      individual depending in part on the exercise mode. We present evidence that
      athletes with a high capillarity and a high muscular oxidative capacity are more
      sensitive to hypoxia.

PMID- 16572375
TI  - 24-hr urinary catecholamine excretion, training and performance in elite
      swimmers.
AB  - The aim of the present study was to investigate the effects of training
      variations on 24-hr urinary noradrenaline (NA) and adrenaline (Ad) levels and the
      adrenaline/noradrenaline (Ad/NA) ratio to search for a possible relationship
      between catecholamine excretion, training, and performance in highly trained
      swimmers. Fourteen swimmers (5 female and 9 male) were tested after 4 weeks of
      intense training (IT), 3 weeks of reduced training (RT), and 5 weeks of low
      training (LT). At the end of each period, the swimmers performed their best event
      at an official competition. Individual performances were expressed as percentage
      of the previous season's best performance. The changes in NA levels after 4 weeks
      of IT were negatively related to changes in training volume (r=-0.70, p<0.01) and
      total training load (r=-0.68, p<0.02). NA levels measured at the end of IT were
      positively related to changes in performance after three weeks of RT (r=0.77,
      p<0.01). The percentage changes in performance between RT and LT were related to
      NA levels at the end of RT (r=0.60; p<0.04). Ad/NA ratios and Ad were related to
      performance (r=0.58, p<0.01; r=52, p<0.01; respectively). The differences in
      Ad/NA ratios and Ad between two consecutive competitions were related to the
      differences in performance (r=0.59, p<0.01; r=0.49, p<0.01; respectively). 24-hr
      NA and the Ad/NA excretion ratio were related to both training variations and
      performance. Thus, 24-hr NA levels and Ad/NA ratio may provide useful markers for
      monitoring training stress in elite swimmers.

PMID- 16572374
TI  - Laboratory running test vs. field roller skiing test in cross-country skiers: a
      longitudinal study.
AB  - Laboratory treadmill running tests are commonly used to assess the effect of
      training programs and to prescribe training intensity for cross-country skiers.
      The present study compared the physiological parameters during a treadmill
      running (R) test and a field roller skiing (RS) test both at the beginning (Beg)
      and at the end (End) of a 6-month specific training program in seven competitive
      cross-country skiers. Oxygen uptake (VO2) and blood lactate concentration ([La])
      were assessed for exercise intensity corresponding to 70%, 80%, 90% of maximal
      heart rate (HRmax) and to HRmax.VO2 was lower for the RS test compared to the R
      test at any HR levels at Beg only (p<0.05). Maximal VO2 increased from Beg to End
      for the RS test only (+23.7+/-10.4; p<0.05). [La] was lower for the R test
      compared to the RS test during both testing periods at 90% HRmax (p<0.05), and no
      significant modification in [La] from Beg to End at any HR levels was observed
      (p>0.05). The [La]/V.O2 curve shifted toward the right from Beg to End to a
      greater extent for the RS test compared to the R test. The present study
      emphasised the importance of exercise specificity in order to assess the effect
      of specific training program in competitive cross-country skiers.

PMID- 16572376
TI  - Arm to leg coordination in elite butterfly swimmers.
AB  - This study proposed the use of four time gaps to assess arm-to-leg coordination
      in the butterfly stroke at increasing race paces. Fourteen elite male swimmers
      swam at four velocities corresponding to the appropriate paces for, respectively,
      the 400-m, 200-m, 100-m, and 50-m events. The different stroke phases of the arm
      and leg were identified by video analysis and then used to calculate four time
      gaps (T1: time gap between entry of the hands in the water and the high break
      even point of the first undulation; T2: time gap between the beginning of the
      hands' backward movement and the low break-even point of the first undulation;
      T3: time gap between the hands' arrival in a vertical plane to the shoulders and
      the high break-even point of the second undulation; T4: time gap between the
      hands' release from the water and the low break-even point of the second
      undulation), the values of which described the changing relationship of arm to
      leg movements over an entire stroke cycle. With increases in pace, elite swimmers
      increased the stroke rate, the relative duration of the arm pull, the recovery
      and the first downward movement of the legs, and decreased the stroke length, the
      relative duration of the arm catch phase and the body glide with arms forward
      (measured by T2), until continuity in the propulsive actions was achieved.
      Whatever the paces, the T1, T3, and T4 values were close to zero and revealed a
      high degree of synchronisation at key motor points of the arm and leg actions.
      This new method to assess butterfly coordination could facilitate learning and
      coaching by situating the place of the leg undulation in relation with the arm
      stroke.

PMID- 16572377
TI  - Consistently high urine specific gravity in adolescent American football players
      and the impact of an acute drinking strategy.
AB  - The purpose of this study was to determine whether high-school football players
      showed risks of fluid deficits during two-a-day training (Part 1), and whether
      implementing a drinking strategy could acutely improve the markers of hydration
      (Part 2). In Part 1, pre-training urine specific gravity (USG) and pre- and post
      training body weight were measured at the morning session for 5 consecutive days
      of two-a-day practices to monitor the hydration status of 13 varsity players. The
      mean pre-training body weight was consistently lower (mean decrease of 0.5 kg,
      p<0.05) following the first day of measurement. Pre-training USG values remained
      consistently high each day (range for daily means: 1.022+/-0.003 to 1.024+/
      0.005). Part 2 consisted of assessing hydration status in 46 varsity and junior
      varsity players prior to morning training during two-a-day training before and
      following implementing a drinking strategy. In association with the strategy,
      mean body weight increased 0.5 kg (p<0.01) and mean USG decreased from 1.021 to
      1.016 (p<0.01) following the drinking protocol. The slight decline in body weight
      and consistently high USG (Part 1) suggested that standard fluid replacement
      strategies were less than optimal for a majority of the players. Implementing a
      drinking strategy appeared to improve hydration status based on changes in body
      weight and USG (Part 2).

PMID- 16572378
TI  - Physical activity and the risk of pneumonia in male smokers administered vitamin
      E and beta-carotene.
AB  - It has been proposed that moderate exercise may enhance the immune system. We
      evaluated whether physical activity at work or at leisure is associated with the
      risk of pneumonia, and whether the antioxidants vitamin E and beta-carotene
      affect pneumonia risk in physically active people. A cohort of 16 804 male
      smokers aged 50-69 years and working at study entry was drawn from the Alpha
      Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which examined the
      effect of vitamin E, 50 mg/day, and beta-carotene, 20 mg/day, on lung and other
      cancers. Physical activity at work, and the type of leisure-time exercise, were
      recorded at study entry. We retrieved the first occurrence of hospital-treated
      pneumonia during a 3-year follow-up from the National Hospital Discharge Register
      (133 cases). Physical activity at work and at leisure had no association with the
      risk of pneumonia. In participants with physically loading jobs, neither vitamin
      E nor beta-carotene affected the risk of pneumonia. In participants carrying out
      moderate or heavy exercise at leisure, beta-carotene had no effect, but vitamin E
      reduced the risk of pneumonia by 50% (95% CI: 16-70%). Previously, exercise has
      been shown to affect diverse laboratory measures of the immune system which are,
      however, only surrogate markers for the resistance to infections. The lack of
      association between physical activity and the risk of pneumonia observed in our
      study emphasizes the problem of drawing conclusions from surrogate end points.
      The finding that vitamin E reduced the risk of pneumonia in persons carrying out
      leisure-time exercise warrants further study.

PMID- 16572380
TI  - The effects of dehydration on brain volume--preliminary results.

PMID- 16572381
TI  - Lipid and lipoprotein changes in premenstrual women following step aerobic dance
      training.

PMID- 16572382
TI  - Selective detection and identification of phosphopeptides by dansyl MS/MS/MS
      fragmentation.
AB  - Protein phosphorylation regulates many cellular processes and pathways, such as
      cell cycle progression, signal transduction cascades and gene expression.
      Selective detection of phosphopeptides from proteolytic digests is a challenging
      and highly relevant task in many proteomics applications. Often phosphopeptides
      are present in small amounts and need selective isolation or enrichment before
      identification. Here we report a novel approach to label selectively phospho-Ser/
      Thr residues by exploiting the features of a novel linear ion trap mass
      spectrometer. Using dansyl labelling and MS3 fragmentation, we developed a method
      useful for the large-scale proteomic profiling of phosphorylation sites. The new
      residues in the sequence were stable and easily identifiable under general
      conditions for tandem mass spectrometric sequencing.

PMID- 16572383
TI  - Turnover of stable carbon isotopes in the muscle, liver, and breath CO2 of
      alpacas (Lama pacos).
AB  - Stable carbon isotope analysis of animal liver and muscle has become a widespread
      tool for investigating dietary ecology. Nonetheless, stable carbon isotope
      turnover of these tissues has not been studied in large mammals except with
      isotopically labelled tracer methodologies, which do not produce carbon half
      lives analogous to those derived from naturalistic diet-switch experiments. To
      address this gap, we studied turnover of carbon isotopes in the liver, muscle,
      and breath CO2 of alpacas (Lama pacos) by switching them from a C3 grass diet to
      an isonitrogenous C4 grass diet. Breath samples as well as liver and muscle
      biopsies were collected and analyzed for up to 72 days to monitor the
      incorporation of the C4-derived carbon. The data suggest half-lives of 2.8, 37.3,
      and 178.7 days for alpaca breath CO2, liver, and muscle, respectively. Alpaca
      liver and muscle carbon half-lives are about 6 times longer than those of
      gerbils, which is about what would be expected given their size. In contrast,
      breath CO2 turnover does not scale readily with body mass. We also note that the
      breath CO2 and liver data are better described using a multiple-pool exponential
      decay model than a single-pool model.

PMID- 16572384
TI  - Survival analysis for recurrent event data: an application to childhood
      infectious diseases.

PMID- 16572386
TI  - Analysis of clinical data with breached blindness.

PMID- 16572389
TI  - Tolls for B cells.
AB  - Priming of naive lymphocytes is important for yielding efficient immune
      responses. Mechanisms controlling this process are also important for preventing
      immune cells from attacking self-antigens. It is well known that signals provided
      by innate immune receptors, such as Toll-like receptors (TLR), are essential to
      induce dendritic cell maturation that subsequently allows the priming of naive T
      cells. In this issue of the European Journal of Immunology, it is shown that TLR
      stimulation effectively potentiates naive human B cell activation and production
      of antibodies in T-dependent immune responses. TLR signals can be delivered to B
      cells directly, or indirectly via cytokines provided by TLR-activated dendritic
      cells.

PMID- 16572390
TI  - The blind-spot of regulatory T cells.
AB  - CD4+ CD25+ Foxp3+ regulatory T cells (Treg) are natural suppressors of
      autoimmunity but they can also dampen the effective clearance of infectious
      organisms. These cells have the potential to be exploited to prevent transplant
      rejection and to treat autoimmune disease. A paper in this issue of the European
      Journal of Immunology details a method to selectively expand antigen-specific
      Treg from a polyclonal Treg population, by using a specific dendritic cell (DC)
      subset. Furthermore, the authors show that such Treg can be used to prevent
      experimental type I diabetes; however, as Treg are positively selected by thymic
      epithelial cells (TEC) on the basis of self-reactivity, they would systematically
      suppress protective immune responses unless their repertoire is devoid of
      recognition towards peripheral antigen-presenting cells. This may be achieved by
      negative selection of developing Treg on thymic DC, thus creating a 'blind-spot'
      corresponding to DC-self-antigens in the mature Treg repertoire. Therefore,
      therapeutic use of DC subsets for the expansion of rare Treg populations should
      take into account this blind-spot, as peptides that are not accessible to thymic
      DC may be significantly more effective for the expansion of Treg.

PMID- 16572391
TI  - On DNA vaccines and prolonged expression of immunogens.
AB  - Persistent hepatitis B virus (HBV) infection represents a major public health
      concern because of its association with chronic liver disease and the propensity
      of the disease to progress to cirrhosis and hepatocellular carcinoma. Despite the
      availability of a prophylactic vaccine effective in a majority of the population,
      alternative vaccination strategies are being sought to induce protective
      responses in healthy non-responders and to boost and broaden T cell responses in
      chronically infected patients, which may lead to a better control of the virus
      and/or its eventual complete clearance. In this issue of the European Journal of
      Immunology immunization of BALB/c mice intramuscularly with a DNA vaccine
      encoding the hepatitis virus B surface antigen (HBsAg) was shown to result in
      prolonged secretion of HBsAg into the serum and the elicitation of HBsAg-specific
      antibodies. In fact, the vaccine was so efficient that the antibodies and HBsAg
      formed circulating immune complexes and induced kidney and liver lesions similar
      to those observed in chronically infected patients. This commentary discusses
      these results in terms of the safety of plasmid DNA-vectored genetic vaccines in
      general, the use of DNA vaccines expressing HBsAg for the treatment of chronic
      hepatitis and the consequences of prolonged immunogen expression for the
      development of protective immune responses.

PMID- 16572392
TI  - Single breath-hold T1 measurement using low flip angle TrueFISP.
AB  - A method for estimating T1 using a single breath-hold, segmented, inversion
      recovery prepared, true fast imaging with steady-state precession (sIR-TrueFISP)
      acquisition at low flip angle (FA) was implemented in this study. T1 values
      measured by sIR-TrueFISP technique in a Gd-DTPA-doped water phantom and the human
      brain and abdomen of healthy volunteers were compared with the results of the
      standard IR fast spin echo (FSE) technique. A good correlation between the two
      methods was observed (R2=0.999 in the phantom, and R2=0.943 in the brain and
      abdominal tissues). The T1 values of the tissues agreed well with published
      results. sIR-TrueFISP enables fast measurements of T1 to be obtained within a
      single breath-hold with good accuracy, which is particularly important for chest
      and abdominal imaging.

PMID- 16572393
TI  - Aging, memory, and language in amnesic H.M.

PMID- 16572395
TI  - Axonemal protofilament ribbons, DM10 domains, and the link to juvenile myoclonic
      epilepsy.
AB  - Juvenile myoclonic epilepsy (JME) is a common neurological disorder that results
      in short uncontrolled muscle contractions and sometimes more severe seizures.
      Genetic studies have suggested that JME may be caused by mutations in EFHC1. The
      Efhc1 protein consists of three DM10 domains and a C-terminal region containing a
      potential Ca2+ -binding motif. In Chlamydomonas, a protein (Rib72) of almost
      identical domain structure is a component of the protofilament ribbons within the
      doublet microtubules of the flagellar axoneme. Here I discuss recent work that
      supports assignment of human Efhc1 as a ciliary component and the resulting
      implications for the mechanism of disease causation.

PMID- 16572396
TI  - Engineering responsiveness to cell culture stresses: growth arrest and DNA damage
      gene 153 (GADD153) and the unfolded protein response (UPR) in NS0 myeloma cells.
AB  - The successful movement of a newly synthesized protein through the endoplasmic
      reticulum (ER) and associated membranous compartments is dependent on appropriate
      recognition by complex processing systems. Failure to perceive appropriately
      processed or modified intermediates in the pathway can initiate a series of
      cellular signaling events (ER stress or unfolded protein response, UPR) that can
      lead to cell apoptosis and loss of biomass in culture processes. We have shown
      that expression of growth arrest and DNA damage gene 153 (GADD153) is associated
      with recognition of damaged or mis-processed proteins within the secretory
      processes of CHO and NS0 myeloma cells. To directly characterize the roles of
      GADD153 in UPR-directed apoptosis, we have generated stable clones of NS0 myeloma
      cells with elevated (constitutive and inducible) and deleted GADD153 expression.
      Although GADD153 is a robust indicator of the onset of ER stress or the UPR,
      GADD153 expression alone is not sufficient to provoke NS0 myeloma apoptosis and
      it is not required for apoptosis to occur.

PMID- 16572394
TI  - Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice
      exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation.
AB  - The myristoylated alanine-rich C kinase substrate (MARCKS) is a primary protein
      kinase C (PKC) substrate in brain thought to transduce PKC signaling into
      alterations in the filamentous (F) actin cytoskeleton. Within the adult
      hippocampus, MARCKS is highly expressed in the dentate gyrus (DG)-CA3 mossy fiber
      pathway, but is expressed at low levels in the CA3-CA1 Schaffer collateral-CA1
      pathway. We have previously demonstrated that 50% reductions in MARCKS expression
      in heterozygous Marcks mutant mice produce robust deficits in spatial reversal
      learning, but not contextual fear conditioning, suggesting that only specific
      aspects of hippocampal function are impaired by reduction in MARCKS expression.
      To further elucidate the role of MARCKS in hippocampal synaptic plasticity, in
      the present study we examined basal synaptic transmission, paired-pulse
      facilitation, post-tetanic potentiation, and long-term potentiation (LTP) in the
      hippocampal mossy fiber-CA3 and Schaffer collateral-CA1 pathways of heterozygous
      Marcks mutant and wild-type mice. We found that LTP is significantly impaired in
      the mossy fiber-CA3 pathway, but not in the Schaffer collateral-CA1 pathway, in
      heterozygous Marcks mutant mice, whereas basal synaptic transmission, paired
      pulse facilitation, and post-tetanic potentiation are unaffected in both
      pathways. These findings indicate that a 50% reduction in MARCKS expression
      impairs processes required for long-term, but not short-term, synaptic plasticity
      in the mossy fiber-CA3 pathway. The implications of these findings for the role
      of the mossy fiber-CA3 pathway in hippocampus-dependent learning processes are
      discussed.

PMID- 16572397
TI  - Malachite green-conjugated microtubules as mobile bioprobes selective for
      malachite green aptamers with capturing/releasing ability.
AB  - We have developed a novel mobile bioprobe using a conjugate of a kinesin-driven
      microtubule (MT) and malachite green (MG) as a platform for capturing MG RNA
      aptamers. The fluorescence of MG increases when it is bound to an MG aptamer,
      allowing MT-MG conjugates to work as sensors of RNA transcripts containing the MG
      aptamer sequence. Kinesin motor proteins provide an effective driving force to
      create mobile bioprobes without any manipulation. Although the fluorescence of a
      small number of MG-binding aptamers is low, the self-organization of tubulins
      into MTs enables the microscopic observation of the bound aptamers by collecting
      them on MTs. We demonstrate that MT-MG conjugates can select target aptamers from
      a transcription mixture and transport them without losing their inherent
      motility. Because the MG aptamer binds MG in a reversible manner, MT-MG
      conjugates can conditionally load and unload the target aptamers. This is one
      advantage of this system over the molecular probes developed previously in which
      reversible unloading is impossible due to high-affinity binding, such as between
      avidin and biotin. Furthermore, an MT-MG conjugate can be used as a platform for
      other MG aptameric sensors with recognition regions for various target analytes
      optimized by further selection procedures. This is the first step to applying
      living systems to in vitro devices. This technique could provide a new paradigm
      of mobile bioprobes establishing high-throughput in vitro selection systems using
      microfluidic devices operating in parallel.

PMID- 16572398
TI  - Broth conditions determining specific cake resistance during microfiltration of
      Bacillus subtilis.
AB  - The effects of broth pH, pressure, temperature, and fermentation medium on
      specific cake resistance were studied for dead-end microfiltration of Bacillus
      subtilis. Decreases in pH and transmembrane pressure decreased the specific cake
      resistance for cells grown in both complex and defined media. With the complex
      medium, the reduction in resistance with temperature decrease did not offset the
      flux decrease caused by the increase in viscosity. The greatest decrease in
      specific cake resistance occurred with adjustment of pH to 7.5 for cells grown in
      defined medium. For those cells the change in pH resulted in aggregation leading
      to a large increase in flux.

PMID- 16572399
TI  - c-Myc-dependent etoposide-induced apoptosis involves activation of Bax and
      caspases, and PKCdelta signaling.
AB  - The c-Myc transcription factor is a key regulator of cell proliferation,
      differentiation, and apoptosis. While deregulation of myc induces programmed cell
      death, defects in the apoptotic program facilitate Myc-driven tumor development.
      We have treated c-Myc inducible mouse cells and rat fibroblasts with different c
      myc status with cytotoxic drugs to explore the effect of c-Myc on drug-induced
      apoptosis. We found that c-Myc overexpression potentiated etoposide-, doxorubicin
      , and cisplatin-induced cell death in mouse fibroblasts. In addition, these drugs
      provoked a strong apoptotic response in c-Myc-expressing cells, but a weak
      apoptosis in c-myc null Rat1 cells. In contrast, staurosporine-induced apoptosis
      was c-Myc-independent, confirming a functional apoptotic pathway in c-myc null
      cells. Apoptosis was paralleled by c-Myc-dependent Bax-activation after etoposide
      and doxorubicin treatment, but not after cisplatin administration. All three
      drugs induced higher caspase activation in c-Myc expressing cells than in c-myc
      null cells. Furthermore, etoposide treatment of c-Myc expressing cells resulted
      in PKCdelta cleavage, while inhibition of PKCdelta reduced etoposide-induced
      apoptosis and prevented Bax activation. Taken together, these findings suggest
      that Bax and caspase activation, together with PKCdelta signaling are involved in
      c-Myc-dependent etoposide-induced apoptosis.

PMID- 16572401
TI  - Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis.
AB  - BACKGROUND: Solitary brain metastases occur in about 50% of patients with brain
      metastases from nonsmall cell lung cancer (NSCLC). The standard of care is
      surgical resection of solitary brain metastases, or stereotactic radiosurgery
      (SRS) plus whole brain radiation therapy (WBRT). However, the optimal treatment
      for the primary site of newly diagnosed NSCLC with a solitary brain metastasis is
      not well defined. The goal was to distinguish which patients might benefit from
      aggressive treatment of their lung primary in patients whose solitary brain
      metastasis was treated with surgery or SRS. METHODS: The cases of 84 newly
      diagnosed NSCLC patients presenting with a solitary brain metastasis and treated
      from December 1993 through June 2004 were retrospectively reviewed at The
      University of Texas M. D. Anderson Cancer Center. All patients had undergone
      either craniotomy (n = 53) or SRS (n = 31) for management of the solitary brain
      metastasis. Forty-four patients received treatment of their primary lung cancer
      using thoracic radiation therapy (median dose 45 Gy; n = 8), chemotherapy (n =
      23), or both (n = 13). RESULTS: The median Karnofsky performance status score was
      80 (range, 60-100). Excluding the presence of the brain metastasis, 12 patients
      had AJCC Stage I primary cancer, 27 had Stage II disease, and 45 had Stage III
      disease. The median follow-up was 9.7 months (range, 1-86 months). The 1-, 2-, 3
      , and 5-year overall survival rates from time of lung cancer diagnosis were
      49.8%, 16.3%, 12.7%, and 7.6%, respectively. The median survival times for
      patients by thoracic stage (I, II, and III) were 25.6, 9.5, and 9.9 months,
      respectively (P = .006). CONCLUSIONS: By applying American Joint Committee on
      Cancer staging to only the primary site, the thoracic Stage I patients in our
      study with solitary brain metastases had a more favorable outcome than would be
      expected and was comparable to Stage I NSCLC without brain metastases. Aggressive
      treatment to the lung may be justified for newly diagnosed thoracic Stage I NSCLC
      patients with a solitary brain metastasis, but not for locally advanced NSCLC
      patients with a solitary brain metastasis.

PMID- 16572402
TI  - Trilateral retinoblastoma.
AB  - BACKGROUND: Trilateral retinoblastoma (TRB) is a syndrome consisting of
      unilateral or bilateral hereditary retinoblastoma (Rb) associated with an
      intracranial neuroblastic tumor. Although its incidence is low, the prognosis is
      very poor. This article reports four cases of TRB and discusses the role of
      neuroimaging screening for early detection. PROCEDURE: From January 1986 to
      December 2003, 470 children with Rb were admitted to the Pediatrics and
      Ophthalmology Departments, A C Camargo Hospital, Sao Paulo, Brazil. RESULTS:
      There were four patients with pineoblastoma, two of whom had a positive familial
      history. The age at diagnosis of Rb was 4, 6, 10, and 24 months while the age of
      diagnosis of TRB was 10, 25, 57, and 72 months. One patient presented TRB at
      initial diagnosis of Rb. Three patients had bilateral disease and all of them had
      one eye enucleated, followed by chemotherapy and/or external beam radiation
      therapy (EBRT). One child with unilateral disease was only submitted to
      enucleation. In spite of intensive treatment, all patients died with progressive
      disease within 7, 8, 12, and 12 months after diagnosis of TRB. CONCLUSIONS: Early
      diagnosis as well as new therapeutic approaches are needed to achieve better
      results.

PMID- 16572403
TI  - Secondary parotid mucoepidermoid carcinoma after TBI and chemotherapy in
      childhood AML.

PMID- 16572404
TI  - Favorable response of intraommaya topotecan for leptomeningeal metastasis of
      neuroblastoma after intravenous route failure.
AB  - A 3-year-old male, diagnosed with stage 4 neuroblastoma, developed recurrent
      leptomeningeal metastasis after multi-modality treatment including multi-agent
      chemotherapy, surgery, high dose chemotherapy plus stem cell rescue, cis-retinoic
      acid and intravenous (IV) topotecan. He then received intraommaya (IO) topotecan
      three times weekly (maximum dose; 0.4 mg). A complete response was achieved by a
      resolution of malignant cells in cerebrospinal fluid and resolution
      leptomeningeal enhancement by brain MRI. Treatment toxicities included low-grade
      fever and minimal headache. The duration of treatment response from IO topotecan
      was 18 weeks. The survival time from CNS recurrence in this patient was 13
      months. We suggest IO topotecan be considered for neoplastic meningitis of tumors
      with known sensitivity to topotecan.

PMID- 16572406
TI  - Attitudes and practices of pediatric oncology providers regarding fertility
      issues.
AB  - PURPOSE: Given the higher survival rates of childhood cancer, health care
      providers must be aware of the side effects of cancer therapies to educate
      patients and provide appropriate interventions to reduce cancer-related
      morbidity. To understand the current practices and attitudes in a pediatric
      hematology/oncology clinic, health care providers were surveyed regarding
      fertility issues pertinent to their patient care. PARTICIPANTS AND INSTRUMENTS:
      In this study, 93.8% (30/32) health care providers in one pediatric
      hematology/oncology department completed a 44-item survey assessing knowledge,
      current practices, obstacles to current practices, perceptions of patient
      differences, and improvements to future practice. RESULTS: The majority of health
      care providers were aware of the adverse effects of alkylating agents (90.7%) and
      of abdominal and pelvic radiation (100.0%) on fertility. However, only half were
      aware of gender differences in gonadotoxicity (50.0%) or knowledgeable of current
      research and technology in fertility preservation (53.3%). While only 34.6% of
      providers currently consulted with specialists, nearly all (92.8%) indicated a
      desire to do so in the future, but 64.3% indicated difficulties in finding proper
      facilities and specialists for their patients. Almost all (96.6%) agreed that
      providers and patient families need more information regarding the effects of
      cancer therapy on fertility. CONCLUSIONS: Surveyed pediatric oncology providers
      considered fertility to be an important issue for childhood cancer patients and
      desired more resources regarding effects on fertility and fertility preservation.
      Greater communication needs to be established between pediatric oncology
      providers and specialists in reproductive medicine and endocrinology to ensure
      adequate professional collaboration and patient referrals.

PMID- 16572407
TI  - Skeletal development of the Mexican spadefoot, Spea multiplicata (Anura:
      Pelobatidae).
AB  - The larval chondrocranium of Spea multiplicata is described, as is the
      development and adult morphology of the skeleton. There are major modifications
      to the larval chondrocranium throughout development, including the presence of
      embryonic trabeculae in young tadpoles and significant reorganization of
      cartilaginous structures at metamorphosis. The first bone to ossify is the
      parasphenoid (Stage 35), followed by the presacral neural arches, ilium, and
      femur (Stage 36). By Stage 39, most of the postcranial elements have begun to
      ossify. Metamorphic climax is accomplished over three Gosner stages (39-41) and
      involves major modifications to the chondrocranium, as well as the appearance of
      three cranial elements (septomaxilla, nasal, and premaxilla). After
      metamorphosis, the exoccipital, vomer, dentary, angulosplenial, squamosal,
      pterygoid, sphenethmoid, ischium, and hyoid begin to ossify. The stapes,
      mentomeckelian, operculum, carpals, and tarsals do not appear until juvenile and
      adult stages. The development of the hyoid and cartilaginous condensations of the
      carpals and tarsals are described. In addition, phenotypic plasticity within the
      genus and the absence of a palatine (= neopalatine) bone are discussed.

PMID- 16572408
TI  - Precursor B lymphoblastic leukemia 32 months after local therapy for a primary
      extramedullary myeloid cell tumor.
AB  - A primary extramedullary myeloid cell tumor (pEMT) of an inguinal lymph node was
      completely excised without subsequent anti-tumor therapy in a 6-year-old child.
      Clinical observation and monitoring of blood and bone marrow (BM) did not reveal
      any pathologic results before 32 months, when a precursor B lymphoblastic
      leukemia was diagnosed. Identical T-cell receptor gamma rearrangement in nodal
      pEMT and in precursor B lymphoblastic leukemia in BM indicates a clonal
      relationship of these two tumors.

PMID- 16572409
TI  - Economic burden associated with breast cancer recurrence: findings from a
      retrospective analysis of health system data.
AB  - BACKGROUND: The economics of breast cancer recurrence are poorly understood. For
      this retrospective cohort study, the authors evaluated the economic burden of
      breast cancer recurrence by using data from a large Midwestern healthcare system.
      METHODS: Women with Stage I or II breast cancer (according to the American Joint
      Commission on Cancer staging criteria) were identified from the tumor registry of
      the Henry Ford Health System. The economic burden of breast cancer recurrence was
      estimated from patient charges (adjusted to 2003 U.S. dollars). RESULTS: From
      1996 to 2002, 1616 patients with early breast cancer were identified, including
      192 patients who had recurrent tumors. Patients with recurrence had significantly
      greater charges in the 6-month and 12-month postrecurrence periods (45,855 U.S.
      dollars and 79,253 U.S. dollars, respectively) compared with the 6-month and 12
      month prerecurrence periods (10,715 U.S. dollars and 12,344 U.S. dollars,
      respectively; both P <.001). This was evident for all recurrence types
      (locoregional, contralateral breast, and distant), but it was most evident for
      distant recurrences. In a regression analysis that was adjusted for baseline
      characteristics, the mean monthly charges were significantly greater for patients
      with recurrence versus patients without recurrence (P <.001), and this was true
      for each recurrence type. For women with recurrence (n = 74 patients), the mean
      charges during the 6-month postrecurrence period were significantly greater than
      mean charges during the initial 6-month period after diagnosis (50,355 U.S.
      dollars vs. 38,254 U.S. dollars; P <.01). Quarterly charges for continuing care
      postrecurrence were significantly greater than prerecurrence charges (4934 U.S.
      dollars vs. 1825 U.S. dollars; P <.001). The mean charges for terminal care were
      significantly greater (P <.01) for women with recurrence (n = 27 patients, 63,434
      U.S. dollars) versus women without recurrence (n = 65 patients, 53,872 U.S.
      dollars). CONCLUSIONS: Patients with early breast cancer who experienced
      recurrence required more costly care than patients who did not develop recurrent
      disease. Therapies that reduce the risk of recurrence may reduce costs
      significantly.

PMID- 16572410
TI  - Early steps in neural development.
AB  - We studied early neurulation events in vitro by transplanting quail Hensen's
      node, central prenodal regions (before the nodus as such develops), or upper
      layer parts of it on the not yet definitively committed upper layer of chicken
      anti-sickle regions (of unincubated blastoderms), eventually associated with
      central blastoderm fragments. We could demonstrate by this quail-chicken chimera
      technique that after the appearance of a pronounced thickening of the chicken
      upper layer by the early inductive effect of neighboring endophyll, a floor plate
      forms by insertion of Hensen's node-derived quail cells into the median part of
      the groove. This favors, at an early stage, the floor plate "allocation" model
      that postulates a common origin for notochord and median floor plate cells from
      the vertebrate's secondary major organizer (Hensen's node in this case). A
      comparison is made with results obtained after transplantation of similar
      Hensen's nodes in isolated chicken endophyll walls or with previously obtained
      results after the use of the grafting procedure in the endophyll walls of whole
      chicken blastoderms.

PMID- 16572411
TI  - Breast cancer incidence after the introduction of mammography screening: what
      should be expected?
AB  - BACKGROUND: A prevalence peak is expected in breast cancer incidence when
      mammography screening begins, but afterward the incidence still may be elevated
      compared with prescreening levels. It is important to determine whether this is
      due to overdiagnosis (ie, the detection of asymptomatic disease that would
      otherwise not have arisen clinically). In the current study, the authors examined
      breast cancer incidence after the introduction of mammography screening in
      Denmark. METHODS: Denmark has 2 regional screening programs targeting women ages
      50 years to 69 years. The programs were initiated in 1991 and 1993, respectively.
      No screening takes place in the 13 other Danish regions. Data regarding incident
      breast cancers detected between 1979 and 2001 were retrieved from the Danish
      Cancer Registry for each screening region and for the rest of Denmark, and time
      trends in rates for women ages 50 years to 69 years were compared. From 1
      program, individual screening data were used to analyze breast cancer incidence
      in women who were never screened, those who were screened for the first time, or
      those who previously were screened. RESULTS: The incidence of breast cancer was
      found to have increased regardless of screening. In the screening regions, a
      marked prevalence peak was observed, and the incidence hereafter was compatible
      with the level indicated by the 95% confidence limits for the regression curves
      for the rates in the prescreening period, taking into account the artificial
      ageing in the program, the influx of newcomers, and variations in the data. Women
      who had undergone previous screening were found to have the same incidence of
      breast cancer as women who were never screened. CONCLUSIONS: The data from the
      current study do not provide evidence of overdiagnosis of invasive breast cancer
      in the 2 Danish screening programs or, if overdiagnosis was found to occur, it
      was only of limited magnitude.

PMID- 16572412
TI  - Guidelines and selection criteria for secondary cytoreductive surgery in patients
      with recurrent, platinum-sensitive epithelial ovarian carcinoma.
AB  - BACKGROUND: The benefit of cytoreductive surgery for patients with recurrent
      epithelial ovarian cancer has not been defined clearly. The objective of this
      study was to identify prognostic factors for survival in patients who underwent
      secondary cytoreduction for recurrent, platinum-sensitive epithelial ovarian
      cancer and to establish generally applicable guidelines and selection criteria.
      METHODS: The authors reviewed all patients who underwent secondary cytoreduction
      for recurrent epithelial ovarian cancer from 1987 to 2001. Potential prognostic
      factors were evaluated in univariate and multivariate analyses. RESULTS: In
      total, 157 patients underwent secondary cytoreduction, and 153 of those patients
      were evaluable. After secondary cytoreduction, the median follow-up was 36.9
      months (range, 0.2-125.6 months), and the median survival was 41.7 months (95%
      confidence interval, 36.0-47.2 months). For patients who had a disease-free
      interval prior to recurrence of between 6 months and 12 months, the median
      survival was 30 months compared with 39 months for patients who had a disease
      free interval between 13 months and 30 months and 51 months for patients who had
      a disease-free interval >30 months (P = .005). For patients who had a single site
      of recurrence, the median survival was 60 months compared with 42 months for
      patients who had multiple sites of recurrence and 28 months for patients who had
      carcinomatosis (P <.001). The median survival for patients who had residual
      disease that measured < or =0.5 cm was 56 months compared with 27 months for
      patients who had residual disease that measured >0.5 cm (P <.001). On
      multivariate analysis, disease-free interval (P = .004), the number of recurrence
      sites (P = .01), and residual disease (P <.001) were significant prognostic
      factors. CONCLUSIONS: In the authors' analysis of secondary cytoreduction for
      recurrent epithelial ovarian cancer, a significant survival benefit was
      demonstrated for residual disease that measured < or = 0.5 cm. The disease-free
      interval and the number of recurrence sites should be used as selection criteria
      for offering secondary cytoreduction.

PMID- 16572413
TI  - BH3-only proteins: integrated control point of apoptosis.
AB  - Bcl-2 family proteins play central roles in the regulation of most, if not all,
      apoptotic pathways, and hence this family plays a critical role in oncogenesis.
      The Bcl-2 homology 3 (BH3)-only members of this family are "proapoptotic,"
      promoting apoptosis by sensing cellular stresses: that is, they are activated or
      induced in response to stress stimuli. These BH3-only proteins then interfere
      with the function of "prosurvival" Bcl-2 family members, thereby promoting the
      progression of apoptosis. It has long been recognized that the induction and
      activation of each of the BH3-only proteins are subject to the type of stress
      stimulus. Although it was originally assumed that all the BH3-only proteins exert
      similar effects on the downstream apoptotic machinery, recent studies have
      uncovered their distinct functional properties, indicating the operation of more
      intricate, versatile control mechanisms of apoptosis. In this review, we will
      summarize recent findings on the diversity in the activation and function of BH3
      only proteins. In particular, we focus on the overlapping and individual roles of
      2 BH3-only proteins, Puma and Noxa, in the context of the apoptotic response
      induced by the tumor suppressor p53.

PMID- 16572414
TI  - Estimates of long-term survival for newly diagnosed cancer patients: a projection
      approach.
AB  - BACKGROUND: Patients with newly diagnosed cancer may request an estimate of their
      prospects for long-term survival. Unfortunately, standard estimates of survival
      may be outdated, because they do not reflect recent advances. The authors present
      a projection method that incorporates trends in survival and provides more up-to
      date estimates of long-term survival for newly diagnosed patients. METHODS: The
      projection method fits a regression model to interval relative survival and
      includes a parameter associated with a trend on diagnosis year. The cumulative
      relative survival rate (CRS) in a target year is calculated by multiplying the
      projected interval survival rates for that year. To investigate the predictive
      ability of the projection approach and to develop model-selection rules, data
      from the Surveillance, Epidemiology, and End Results Program and the Connecticut
      tumor registry were used to recreate data that were available at a particular
      time in the past, and those data were used to project survival for specified
      target years. RESULTS: The projection method was better at predicting the
      survival of recently diagnosed patients than current methods, especially long
      term survival for patients who had disease sites with an increasing and stable
      trend in survival. The authors predicted that the 15-year CRS for patients who
      were diagnosed in 2003 will be 61% for all cancer sites combined, 57% for
      colorectal cancer, 82% for female breast cancer, 53% for ovarian cancer, and 97%
      for prostate cancer. CONCLUSIONS: Although the projection method was more
      speculative than other methods that are aligned more closely with current
      observed data, it offered the possibility of providing improved estimates of long
      term survival for recently diagnosed patients. Caution should be used when
      applying these methods for cancer sites where there has been a dramatic uptake of
      screening, e.g., prostate cancer, for which the projected results may be overly
      optimistic.

PMID- 16572415
TI  - Leaving home after cancer in childhood: a measure of social independence in early
      adulthood.
AB  - BACKGROUND: Previous studies on psychosocial outcomes for childhood and
      adolescent cancer survivors have found diverse results concerning social
      independence. As a measure of social independence, we investigated whether cancer
      survivors displayed the same patterns of leaving home as population-based control
      group. PROCEDURE: We identified 1,597 patients in the Danish Cancer Register,
      born in 1965-1980, in whom a primary cancer was diagnosed before they reached the
      age of 20 in the period 1965-1995. The patients were compared with a random
      sample of the general population (n = 43,905) frequency matched on sex and date
      of birth. By linking the two cohorts to registers in Statistics Denmark, we
      obtained socioeconomic data for the period 1980-1997. The relative risk for
      leaving home was estimated with discrete-time Cox regression models. RESULTS: The
      risk for leaving home of survivors of hematological malignancies and solid tumors
      did not differ significantly from that of the control cohort. Adjustments for
      possible socioeconomic confounders did not change this pattern. In contrast,
      survivors of central nervous system (CNS) tumors had a significantly reduced risk
      for leaving home, which was most pronounced for men (relative risk, men: 0.66;
      95% confidence interval, 0.55-0.80; women: 0.88, 95% confidence interval, 0.80
      0.97). CONCLUSION: Overall, the psychosocial effects of cancer in childhood or
      adolescence and its treatment on the survivor and family did not appear to impede
      social independence in early adulthood, except for survivors of CNS tumors.

PMID- 16572416
TI  - Comparison of disruption procedures for enumeration of activated sludge floc
      bacteria by flow cytometry.
AB  - BACKGROUND: In a wastewater treatment plant, the degradation process is performed
      by a variable and mixed community of microorganisms in an aerobic aquatic
      environment. The activated-sludge process is based on the formation of strong
      microbial flocs where many bacteria are attached to sludge flocs. METHODS:
      Cytometric analysis requires an homogeneous cell suspension and so detachment of
      bacteria from flocs is required. In this study, sonication and homogenization
      were compared to find the most adequate pretreatment method for bacterial
      cytometric analysis in activated sludge samples. Bacterial viability was tested
      with a nucleic acid double-staining (NADS) protocol (Barbesti et al., Cytometry
      2000;40:214-218) and on flow cytometry. RESULTS: Each method showed a good
      efficiency in terms of bacterial detachment; thus finally, the choice of which
      could be the best treatment method was based on both viability results and
      analysis rapidity. On the basis of the degree of cell detachment and viability,
      the maximum value was obtained by sonication (2 x 45''). CONCLUSIONS: The use of
      flow cytometry in conjunction with fluorescent dyes and an adequate pretreatment
      represents a useful method to rapidly detect and enumerate bacteria in activated
      sludge samples.

PMID- 16572418
TI  - Flow rate calibration. III. The use of stabilized biostandards to calibrate the
      flow rate and calculate absolute CD4+ T-cell counts.
AB  - BACKGROUND: We have previously reported a flow rate calibration method for the
      determination of absolute CD4(+) T-lymphocyte counts that removes the need for
      the addition of latex beads to each sample. However, a limitation with this
      approach is that a calibration factor (CF) needs to be applied to adjust for
      differences in viscosity between latex bead suspensions and biological specimens.
      We have also demonstrated the value of using stabilized whole blood samples in
      external quality assessment (EQA) studies; such samples have a stable absolute
      lymphocyte count for over 1 year, at 4 degrees C. It was successfully
      demonstrated that this material can be used as a flow rate biocalibration (FRB)
      material for use as a flow cytometric control to provide a sample with a known
      CD4(+) T-lymphocyte count. Such material has advantages over latex bead
      technology as it can act as a full process control as well as having the same
      matrix and viscosity characteristics as the test material, thus removing the need
      for a CF. METHODS: In this study, we have analyzed 268 consecutive normal,
      abnormal, and HIV(+) samples using FRB, incorporating the PanLeucoGating approach
      and compared this to the MultiSet method, defined as the predicate. RESULTS:
      Percentage similarity statistics revealed the following: 0-3,000 CD4(+) cells/mul
      mean percentage difference (MPD; bias) 1.2%, 95% CI of 5.6-8%; 0-200 CD4(+)
      cells/microl MPD of 1.25%, 95% CI of 11.63-14.13%; 201-500 CD4(+) cells/microl
      MPD of 1%, 95% CI of 4.6-6.6%. DISCUSSION: This study demonstrates that
      stabilized whole blood can be used for FRB. It has the advantage of being a full
      process control, in addition to costing less than latex beads with highly
      comparable results. As bench top flow cytometers are extremely stable, this is a
      low cost and robust alternative to bead based methods for generating absolute CD4
      counts.

PMID- 16572417
TI  - Flow cytometric features of angioimmunoblastic T-cell lymphoma.
AB  - BACKGROUND: The immunophenotypic features of angioimmunoblastic T-cell lymphoma
      (AILT) have not been well described. METHODS: We retrospectively reviewed our
      institutional experience with the flow cytometric features of 16 cases of AILT.
      RESULTS: Multiparameter flow cytometry was able to identify a distinct population
      of immunophenotypically aberrant T cells in 15 of 16 cases. In 13 lymph node
      specimens, the neoplastic cells ranged from 1.9 to 87% (median 23%) of cells. The
      ratio of reactive to neoplastic T cells ranged from 0.01 to 20 (median 1.5);
      reactive T cells outnumbered neoplastic in 9/13 (69%) cases. The neoplastic
      populations expressed CD2, CD4, CD5, and CD45RO in all cases, lacked expression
      of CD8 and CD56 in all cases, and showed negative or dim surface CD3 in most
      cases. CD10 was expressed by the neoplastic populations in 11 of 14 cases at
      diagnosis; in 3 of these 11 only a subpopulation of the neoplastic cells was
      CD10(+). CD10 tended to be absent on neoplastic cells in staging bone marrows.
      The neoplastic population in all but one of the 15 positive cases possessed
      multiple immunophenotypic abnormalities and these were generally retained during
      the follow-up analyses of several cases. CONCLUSIONS: These results indicate the
      potential utility of flow cytometry in the diagnosis and follow-up of AILT.

PMID- 16572419
TI  - Safety assessment of intensive induction with vincristine, ifosfamide,
      doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO
      E.W.I.N.G. 99 clinical trial.
AB  - BACKGROUND: The EUROpean Ewing tumour Working Initiative of National Groups 1999
      (EURO-E.W.I.N.G. 99) protocol prescribes six courses of vincristine, ifosfamide,
      doxorubicin, and etoposide (VIDE) as intensive induction chemotherapy for Ewing
      tumors (ET). Granulocyte-colony stimulating factor (G-CSF) is recommended.
      Adverse reactions (AR) were evaluated; quality assurance of data collection
      reviewed. PROCEDURE: Safety data from 4,746 courses of VIDE in 851 patients less
      than 50 years with ET were collected using a checklist and evaluated using
      descriptive statistics with sub-groups including gender, age, and tumor volume,
      analyzed by Wilcoxon and Kruskal-Wallis tests. RESULTS: Myelosuppression and
      infections were the major AR but with appropriate supportive therapy targeted
      dose intensity was maintained. Five VIDE-related deaths with three due to sepsis
      were reported. Renal and cardiac toxicity were reflected by glomerular filtration
      rate (GFR) <39 ml/min/1.73 m2 in 0.1%, tubular phosphate reabsorption < or = 0.80
      in 1.9%, and left ventricular shortening fracture <28% in 2.5% VIDE courses.
      Statistically significant gender-associated AR concerning hemoglobin and
      platelets were observed with females > males as were age-associated AR concerning
      hemoglobin, WBC, platelets, stomatitis, and vomiting with AR decreasing with age,
      that is, children > adolescents > adults. No association of AR to tumor volume
      was found. In VIDE courses with and without G-CSF, neutropenia-related fever in
      60.8% and 65.8%, and infection in 54.7% and 61.0% courses, respectively, were
      recorded. CONCLUSIONS: AR under VIDE remained within the expected range. Some AR,
      for example, hematotoxicity were significantly influenced by age and gender but
      not by tumor volume. G-CSF did not significantly influence neutropenia-related
      fever and infection. Solicited safety collection with checklists adequately
      reflects the burden per course.

PMID- 16572420
TI  - 5-fluorouracil-related gene expression levels in primary colorectal cancer and
      corresponding liver metastasis.
AB  - Gene expression levels of thymidylate synthase (TS), dihydropyrimidine
      dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl
      transferase (OPRT) have been shown to be associated with response to 5
      fluorouracil-based therapies. Analyzing these gene expression levels in liver
      metastases is important to obtain the best prediction of therapy. Our aim was to
      determine how TS, DPD, TP and OPRT gene expression levels in primary colorectal
      cancer (CRC) were related to those in liver metastases. Formalin-fixed, paraffin
      embedded tumor specimens from 31 pairs of primary CRC and corresponding liver
      metastases were dissected by using laser-captured microdissection. RNA was
      extracted and cDNA was prepared by reverse-transcription. Quantitation of target
      gene and internal reference gene was performed using real-time PCR. No
      significant difference was seen between median mRNA expression levels of TS, DPD,
      TP and OPRT in primary cancer and those in corresponding liver metastases (median
      value: TS 1.48 vs. 1.43; p=0.92, DPD 0.19 vs.0.12; p=0.10, TP 1.20 vs. 0.98;
      p=0.39, OPRT 1.17 vs. 0.95; p=0.10). When matched tissue sets were compared on an
      individual basis, there was a significant correlation for TS mRNA expression
      between primary cancer and corresponding liver metastases (rs=0.52, p=0.0026).
      However, no correlation was seen between matched sets for DPD, TP or OPRT.
      Significant correlation was seen between DPD and TP expression levels in both
      primary CRC (rs=0.38, p=0.03) and liver metastases (rs=0.72, p<0.0001). A good
      prediction of TS mRNA levels in liver metastases can be obtained by measuring
      those of primary CRC, although no correlation was seen for DPD, TP and OPRT.

PMID- 16572421
TI  - IRS-1-Rad51 nuclear interaction sensitizes JCV T-antigen positive medulloblastoma
      cells to genotoxic treatment.
AB  - The large T-antigen from human polyomavirus JC (JCV T-antigen) is suspected to
      play a role in malignant transformation. Previously, we reported that JCV T
      antigen requires the presence of a functional insulin-like growth factor I
      receptor (IGF-IR) for transformation of fibroblasts and for survival of
      medulloblastoma cell lines; that IGF-IR is phosphorylated in medulloblastoma
      biopsies and that JCV T-antigen inhibits homologous recombination-directed DNA
      repair, causing accumulation of mutations. Here we are evaluating whether JCV T
      antigen positive and negative mouse medulloblastoma cell lines, which
      significantly differ in their tumorigenic properties, are also different in their
      abilities to repair double strand breaks of DNA (DSBs). Our results show that
      despite much stronger tumorigenic potential, JCV T-antigen positive
      medulloblastoma cells are more sensitive to genotoxic agents (cisplatin and gamma
      irradiation). Subsequent analysis of DNA repair of DSBs indicated that homologous
      recombination-directed DNA repair (HRR) was selectively attenuated in JCV T
      antigen positive medulloblastoma cells. JCV T-antigen did not affect HRR
      directly. In the presence of JCV T-antigen, insulin receptor substrate 1 (IRS-1)
      translocated to the nucleus where it co-localized with Rad51, possibly
      attenuating HRR.

PMID- 16572423
TI  - The antimicrobial peptide, lactoferricin B, is cytotoxic to neuroblastoma cells
      in vitro and inhibits xenograft growth in vivo.
AB  - Antimicrobial peptides have been shown to exert cytotoxic activity towards cancer
      cells through their ability to interact with negatively charged cell membranes.
      In this study the cytotoxic effect of the antimicrobial peptide, LfcinB was
      tested in a panel of human neuroblastoma cell lines. LfcinB displayed a selective
      cytotoxic activity against both MYCN-amplified and non-MYCN-amplified cell lines.
      Non-transformed fibroblasts were not substantially affected by LfcinB. Treatment
      of neuroblastoma cells with LfcinB induced rapid destabilization of the
      cytoplasmic membrane and formation of membrane blebs. Depolarization of the
      mitochondria membranes and irreversible changes in the mitochondria morphology
      was also evident. Immuno- and fluorescence-labeled LfcinB revealed that the
      peptide co-localized with mitochondria. Furthermore, treatment of neuroblastoma
      cells with LfcinB induced cleavage of caspase-6, -7 and -9 followed by cell
      death. However, neither addition of the pan-caspase inhibitor, zVAD-fmk, or
      specific caspase inhibitors could reverse the cytotoxic effect induced by LfcinB.
      Treatment of established SH-SY-5Y neuroblastoma xenografts with repeated
      injections of LfcinB resulted in significant tumor growth inhibition. These
      results revealed a selective destabilizing effect of LfcinB on two important
      targets in the neuroblastoma cells, the cytoplasmic- and the mitochondria
      membrane.

PMID- 16572422
TI  - Serum C-peptide levels and breast cancer risk: results from the European
      Prospective Investigation into Cancer and Nutrition (EPIC).
AB  - It has been hypothesized that chronic hyperinsulinemia, a major metabolic
      consequence of physical inactivity and excess weight, might increase breast
      cancer risk by direct effects on breast tissue or indirectly by increasing
      bioavailable levels of testosterone and estradiol. Within the European
      Prospective Investigation into Cancer and Nutrition (EPIC), we measured serum
      levels of C-peptide--a marker for pancreatic insulin secretion--in a total of
      1,141 incident cases of breast cancer and 2,204 matched control subjects.
      Additional measurements were made of serum sex hormone binding globulin (SHBG)
      and sex steroids. Conditional logistic regression models were used to estimate
      breast cancer risk for different levels of C-peptide. C-peptide was inversely
      correlated with SHBG and hence directly correlated with free testosterone among
      both pre and postmenopausal women. C-peptide and free estradiol also correlated
      positively, but only among postmenopausal women. Elevated serum C-peptide levels
      were associated with a nonsignificant reduced risk of breast cancer diagnosed up
      to the age of 50 years [odds ratio (OR)=0.70, (95% confidence interval (CI), 0.39
      1.24); ptrend=0.05]. By contrast, higher levels of C-peptide were associated with
      an increase of breast cancer risk among women above 60 years of age, however only
      among those women who had provided a blood sample under nonfasting conditions
      [OR=2.03, (95% CI, 1.20-3.43); ptrend=0.01]. Our results do not support the
      hypothesis that chronic hyperinsulinemia generally increases breast cancer risk,
      independently of age. Nevertheless, among older, postmenopausal women,
      hyperinsulinemia might contribute to increasing breast cancer risk.

PMID- 16572424
TI  - In-vivo measurements of the dielectric properties of breast carcinoma xenografted
      on nude mice.
AB  - A developing method of cancer detection is to use electromagnetic waves to
      compare the dielectric properties of normal and cancerous tissue. Because most of
      the previous studies consisted of dielectric measurements taken ex-vivo, this
      study investigated the advantages of in-vivo measurements, obtained using the
      newly developed insertion-type planar probe, through the measurements of cancer
      (MDA MB 231), which was cultivated and implanted into the mammary fat pad of nude
      mice. Reflection coefficients were obtained in the broadband frequency range from
      0.5 to 30 GHz, from which broadband complex permittivity data was extracted.
      Complex permittivity, in addition to other parameters such as conductivity and
      characteristic frequency, were used to make comparisons between cancerous tissue,
      normal muscle tissue and fat tissue, as well as comparisons between in-vivo and
      ex-vivo measurements. This study investigated the suitability of in-vivo cancer
      detection using microwaves with the newly developed insertion-type planar probe.
      Results showed that both sensitivity and specificity of the current method was
      97%. In addition, predictive values were 99% for the positive and 94% for the
      negative, thus greatly enhancing the practicality of this method. In conclusion,
      it was demonstrated that in-vivo measurements are highly beneficial in studying
      the potential of microwaves as a diagnostic tool of breast cancer, especially in
      combination with the newly developed insertion-type planar probe.

PMID- 16572425
TI  - Randomized controlled trial of human papillomavirus testing versus Pap cytology
      in the primary screening for cervical cancer precursors: design, methods and
      preliminary accrual results of the Canadian cervical cancer screening trial
      (CCCaST).
AB  - Since infection with oncogenic human papillomavirus (HPV) has been considered a
      necessary cause of cervical cancer, tests for oncogenic HPV types have been
      proposed as adjuncts or replacements to Pap cytology. We designed the Canadian
      Cervical Cancer Screening Trial (CCCaST) to compare the relative efficacy of HPV
      DNA testing and Pap cytology in primary screening for cervical cancer and its
      high-grade precursors. CCCaST randomized women aged 30-69 years in Montreal
      (Quebec) and in St. John's (Newfoundland) to 1 of 2 screening groups: focus on
      Pap (conventional) or focus on HPV testing (Hybrid Capture 2). Women in both arms
      received both tests, but were randomized as to their order, the first test being
      the index test. Women with an abnormal Pap test or a positive HPV test underwent
      colposcopy and biopsy, as did a random sample of women with a negative index
      test. CCCaST enrolled 9,667 women between October 2002 and October 2004. At
      enrolment, 2.8% had an abnormal Pap test, 6.1% had a positive HPV test and 1.1%
      were abnormal in both tests. ASC-US was the most frequent cytological
      abnormality, representing 64% of abnormal Pap results. The frequency of abnormal
      Pap and HPV results decreased with increasing age and the proportion of HPV
      positive results increased with the severity of Pap abnormality. Efficacy
      analysis will determine if the extra referrals with HPV DNA testing will
      translate into a relevant increase in high-grade cervical cancer precursor
      detection. Because of its design, CCCaST will provide sound evidence for
      formulating cervical cancer screening strategies.

PMID- 16572427
TI  - Noninvasive diagnosis of nasopharyngeal carcinoma: nasopharyngeal brushings
      reveal high Epstein-Barr virus DNA load and carcinoma-specific viral BARF1 mRNA.
AB  - Nasopharyngeal carcinoma (NPC) is the most prevalent ENT-tumour in Indonesia. We
      investigated the primary diagnostic value of Epstein-Barr virus (EBV) DNA load
      and mRNA detection in noninvasive nasopharyngeal (NP) brushings, obtained
      prospectively from consecutive Indonesian ENT-patients with suspected NPC (N=106)
      and controls. A subsequent routine NP biopsy was taken for pathological
      examination and EBER-RISH, yielding 85 confirmed NPC and 21 non-NPC tumour
      patients. EBV DNA and human DNA load were quantified by real-time PCR. NP
      brushings from NPC patients contained extremely high EBV DNA loads compared to
      the 88 non-NPC controls (p<0.0001). Using mean EBV DNA load in controls plus 3 SD
      as cut-off value, specificity, sensitivity, positive and negative predictive
      values were 98, 90, 97 and 91%, respectively. Epstein-Barr nuclear antigen 1
      (EBNA1) and the carcinoma-specific BARF1 mRNA were detected by nucleic acid
      sequence based amplification and found in 86 and 74% of NP brushings, confirming
      NPC tumour cell presence. EBV RNA positivity was even higher in fresh samples
      stored at -80 degrees C until RNA expression analyses (88% for both EBNA1 and
      BARF1). EBV RNA-negative NP brushings from proven NPC cases had the lowest EBV
      DNA loads, indicating erroneous sampling. No EBV mRNA was detected in NP
      brushings from healthy donors and non-NPC patients. In conclusion, EBV DNA load
      measurement combined with detection of BARF1 mRNA in simple NP brushings allows
      noninvasive NPC diagnosis. It reflects carcinoma-specific EBV involvement at the
      anatomical site of tumour development and reduces the need for invasive biopsies.
      This procedure may be useful for confirmatory diagnosis in large serological NPC
      screening programs and has potential as prognostic tool.

PMID- 16572426
TI  - Tissue array analysis of expression microarray candidates identifies markers
      associated with tumor grade and outcome in serous epithelial ovarian cancer.
AB  - Molecular profiling is a powerful approach to identify potential clinical markers
      for diagnosis and prognosis as well as providing a better understanding of the
      biology of epithelial ovarian cancer. On the basis of the analysis of HuFL
      expression data, we have previously identified genes that distinguish low
      malignant potential and invasive serous epithelial ovarian tumors. In this study,
      we used immunohistochemistry to monitor a subset of differently expressed
      candidates (Ahr, Paep, Madh3, Ran, Met, Mek1, Ccne1, Ccd20, Cks1 and Cas). A
      tissue array composed of 244 serous tumors of different grades (0-3) and stages
      (I-IV) was used in this analysis. All markers assayed presented differential
      protein expression between serous tumors of low and high grade. Significant
      differences in Ccne1 and Ran expression were observed in a comparison of low
      malignant potential and grade 1 tumor samples (p<0.01). In addition, irrespective
      of the grade, Ccne1, Ran, Cdc20 and Cks1 showed significant differences of
      expression in association with the clinical stage of disease. While high level of
      Ccne1 have previously been associated with poor outcomes, here we found that high
      level of either Ran or Cdc20 appear to be more tightly associated with a poor
      prognosis (p<0.001, 0.03, respectively). The application of these biomarkers in
      both the initial diagnosis and prognostic attributes of patients with epithelial
      ovarian tumors should prove to be useful in patient management.

PMID- 16572428
TI  - Sun exposure and host phenotype as predictors of cutaneous melanoma associated
      with neval remnants or dermal elastosis.
AB  - Recent research suggests that cutaneous melanomas may arise through 2 distinct
      pathways, characterized by chronic sun exposure on one hand and nevus-prone
      phenotype of the host on the other. Two histological characteristics of melanoma
      consistent with these divergent origins are dermal elastosis in adjacent skin and
      neval remnants contiguous with the tumor, respectively. To further explore causal
      heterogeneity in melanoma, we compared sun exposure histories and phenotypic
      characteristics among a population-based sample of patients newly diagnosed with
      cutaneous melanoma with and without contiguous neval remnants or dermal
      elastosis. Tissue blocks were obtained for 141 patients: 53 with superficial
      spreading melanoma (SSM) of the back, 42 with SSM of head and neck (H & N), and
      39 and 7 with lentigo maligna/lentigo maligna melanoma (LM/LMM) of the H & N and
      back, respectively. Melanomas of the H & N were less likely than those on back to
      have neval remnants (adjusted OR 0.6, 95% CI 0.3-1.4), but were significantly
      more likely to have dermal elastosis (adjusted OR 9.3, 95% CI 3.5-25). In site
      specific analyses, we found that H & N melanomas with neval remnants were more
      likely than those without neval remnants to arise in people with more than 60
      nevi (adjusted OR 2.1, 95% CI 0.3-14.3), but were less likely to arise in those
      with more than 20 actinic keratoses. Less marked associations were observed for
      melanomas of the back. High levels of sun exposure strongly predicted dermal
      elastosis for H & N melanomas (OR 22.5, 95% CI 2.1-245), but not for melanomas of
      the back (OR 2.1, 95% CI 0.4-11). We conclude that melanomas with different
      histologic characteristics have different risk factor profiles, particularly on
      the head and neck. These data accord with the hypothesis that melanomas arise
      through different causal pathways.

PMID- 16572429
TI  - Remission induction chemotherapy induces in vivo caspase-dependent apoptosis in
      bone marrow acute myeloid leukemia blast cells and spares lymphocytes.
AB  - BACKGROUND: The goal of new therapeutic strategies is to adapt the treatment of
      acute myeloid leukemia (AML) patients to the prognostic and/or to the
      hematological response. METHODS: We analyzed in vivo apoptosis induction in blast
      cells and in lymphocytes of AML patients receiving remission induction treatment.
      RESULTS: We show, on 12 peripheral blood samples, that the increase of peripheral
      apoptotic blast cells cannot be considered as the earliest marker of the
      treatment efficiency, because the significant increase of apoptosis followed the
      white blood cell and the peripheral blast cell count reductions, probably due to
      an efficient clearance of circulating apoptotic cells. Furthermore, the study of
      65 bone marrow samples at d15 showed that the treatment induced apoptosis of
      blast cells while sparing the lymphocytes. This apoptosis was evidenced both at
      the caspase and at the membrane levels using respectively fmk-VAD-FITC and
      Annexin V binding assays. We found that less than 50% of apoptosis, measured with
      the fmk-VAD-FITC, in the d15 residual bone marrow blast cells, correlated with
      lower disease-free survival probability. CONCLUSION: More studies are needed in
      larger series and earlier during the remission induction treatment to confirm the
      possible prognostic significance of in vivo apoptosis induction.

PMID- 16572430
TI  - Management algorithm in pulmonary atresia with intact ventricular septum.
AB  - Pulmonary atresia with intact ventricular septum (PAIVS) is a disease with
      remarkable morphologic variability, affecting not only the pulmonary valve but
      also the tricuspid valve, the RV cavity and coronary arteries. With advances in
      interventional techniques and congenital heart surgery, the management of PAIVS
      continues to evolve. This review is an attempt at providing a practical approach
      to the management of this disease. The basis of our approach is morphologic
      classification as derived from echocardiography and angiography. Group A,
      patients with good sized RV and membranous atresia, the primary procedure at
      presentation is radiofrequency (RF) valvotomy. Often it is the only procedure
      required in this group with the most favourable outcome. Patients with severely
      hypoplastic RV (Group C) are managed along the lines of hearts with single
      ventricle physiology. The treatment at presentation is patent ductus arteriosus
      (PDA) stenting with balloon atrial septostomy or conventional modified Blalock
      Taussig (BT) shunt. Bidirectional Glenn shunt may be done 6-12 months later
      followed by Fontan completion after a suitable interval. Patients in Group B, the
      intermediate group, are those with borderline RV size, usually with attenuated
      trabecular component but well developed infundibulum. The treatment at
      presentation is RF valvotomy and PDA stenting +/- balloon atrial septostomy.
      Surgical re-interventions are not uncommonly required viz. bidirectional Glenn
      shunt when the RV fails to grow adequately (11/2 - ventricle repair) and right
      ventricular outflow tract (RVOT) reconstruction for subvalvar obstruction or
      small pulmonary annulus. Catheter based interventions viz. repeat balloon
      dilatation or device closure of patent foramen ovale (PFO) may also be required
      in some patients.

PMID- 16572431
TI  - Time frame of mitral cell development in the mice olfactory bulb.
AB  - Along with tufted cells, mitral cells are the principal projection neurons in the
      olfactory bulb (OB). During the development of the OB, mitral cells migrate from
      the ventricular zone to the intermediate zone, where they begin to send axons
      along the lateral olfactory tract (LOT) to the cortical olfactory zones.
      Subsequently, they lose their tangential orientation, enabling them to make
      contact with the axons of the olfactory sensory neurons (OSN) that innervate the
      whole OB. Here, we investigated the distinct morphological features displayed by
      developing mitral cells and analyzed the relationship between the changes
      undertaken by these neurons and the arrival of the OSN axons. Immunostaining for
      specific markers of developing axons and dendrites, coupled with the use of
      fluorescent tracers, revealed the morphological changes, the continuous
      reorientation, and the final refinement that these cells undergo. We found that
      some of these changes are dependent on the arrival of the OSN axons. Indeed, we
      identified three main chronological events: 1) newly generated neurons become
      established in the intermediate zone and project to the LOT; 2) the cells
      reorient and spread their dendrites at the same time as OSN axons penetrate the
      OB (this is a sensitive period between embryonic day (E)15-16, in which the
      arrival of afferents establishes a spatial and temporal gradient that facilitates
      protoglomerulus and glomerulus formation); and 3) final refinement of the
      radially orientated cells to adopt a mature morphology. These results suggest
      that both afferent inputs and intrinsic factors participate to produce the well
      defined sensory system.

PMID- 16572432
TI  - Expression of the vesicular glutamate transporter vGluT2 in a subset of cones of
      the mouse retina.
AB  - Cone photoreceptors have a continuous release of glutamate that is modulated by
      light. Vesicular glutamate transporters (vGluT) play an essential role for
      sustaining this release by loading synaptic vesicles in the cone synapse, the so
      called cone pedicle. In the present study mouse retinas were immunostained for
      vGluT1 and vGluT2. vGluT1 was localized to all cone pedicles and rod spherules,
      whereas vGluT2 was found in only 10% of the cone pedicles. The vGluT2-expressing
      cones were characterized in more detail. They are distributed in a regular array,
      suggesting they are a distinct type. Their proportion does not differ between
      dorsal (L-cone-dominated) and ventral (S-cone-dominated) retina, and they are not
      the genuine blue cones of the mouse retina. During development, vGluT1 and vGluT2
      expression in cones starts at around P0 and right from the beginning vGluT2 is
      only expressed in a subset of cones. Bipolar cells contact the vGluT2-expressing
      cones and other cones nonselectively. The possible functional role of vGluT2
      expression in a small fraction of cones is discussed.

PMID- 16572433
TI  - Development-dependent and -independent ubiquitin expression in divisions of the
      cockroach mushroom body.
AB  - It has been proposed that the alpha and beta divisions of the mushroom bodies
      support intermediate and long-term memory whereas the gamma lobes support short
      term memory. Here we investigate developmentally dependent versus developmentally
      independent alterations of mushroom body structure with special emphasis on its
      lobes. We show that in the cockroach mushroom bodies there are two types of
      plastic remodeling. One is developmental, in which episodic addition of new
      circuitry to the alpha and beta lobes is accomplished by newly born Kenyon cells.
      The second is revealed as a persistent alteration of structure within the gamma
      lobe. In the alpha/beta lobes, newly generated Kenyon cell axons extend glutamate
      immunoreactive collaterals across layers of the axons of mature Kenyon cells. At
      specific times in each developmental episode (instar) these collaterals express
      ubiquitin, undergo localized degeneration, and are scavenged by glial cells. In
      contrast, the mature Kenyon cells that comprise the gamma lobe express detectable
      ubiquitin throughout each developmental episode. This pattern of ubiquitin
      expression suggests that the gamma lobe circuitry undergoes continuous
      modification independent of development.

PMID- 16572434
TI  - Neuropeptide FF distribution in the human and rat forebrain: a comparative
      immunohistochemical study.
AB  - Neuropeptide FF (NPFF) is an octapeptide implicated in a variety of physiological
      functions, including nociception, cardiovascular responses, and neuroendocrine
      regulation. The NPFF gene and its mRNA are highly conserved across species. A
      comparative study of NPFF distribution in the human and rat forebrain was carried
      out by using single NPFF and double NPFF + vasopressin (VP) immunohistochemistry.
      NPFF is extensively localized within neurochemical circuits of human and rat
      forebrain. Semiquantitative analysis revealed that the densities of NPFF cells
      and fibers in many forebrain nuclei in the human correlate well with those
      observed for the same structures in the rat. High numbers of NPFF positive
      neurons in the dorsomedial hypothalamic nucleus and a dense plexus of NPFF fibers
      surrounding the fornix within the bed nucleus of the stria terminalis were
      identified in the human and rat forebrain. Within the hypothalamus of both
      species, dense NPFF innervation was observed in the perinuclear zone of the
      supraoptic nucleus (SO) just dorsolateral to the VP-positive neurons. Extensive
      NPFF innervation of ventricular ependyma and brain microvasculature were common
      for both species. At the same time, obvious differences in NPFF localization
      between the two species were also apparent. For example, in contrast to the rat
      SO, no NPFF- or NPFF- + VP-immunostained cells were observed in the human SO.
      Knowledge of NPFF neuroanatomical localization in the human brain and the
      relationship of these observations to those in the rat brain may provide insight
      into the role of this peptide in central cardiovascular and neuroendocrine
      regulation.

PMID- 16572435
TI  - Differentiation of mesenchymal stem cells into osteoblasts on honeycomb collagen
      scaffolds.
AB  - Tissue engineering using living cells is emerging as an alternative to tissue or
      organ transplantation. The adult mesenchymal stem cells can be differentiated
      into multilineage cells, such as adipocytes, chondrocytes, or osteoblasts when
      cultured with specific growth factors. In the present investigation, we have
      studied the effect of honeycomb collagen scaffolds for the adhesion,
      differentiation and proliferation of bone marrow-derived mesenchymal stem cells
      into osteoblasts. Mesenchymal stem cells were isolated from 6-week old albino rat
      femur bone marrow, and cultured in alpha-MEM medium without beta-glycerophosphate
      and dexamethasone. Honeycomb collagen discs were prepared from bovine dermal
      atelocollagen, cross-linked by UV-irradiation and sterilized by heat. The
      honeycomb discs were placed on the culture dishes before seeding the stem cells.
      The cells attached quickly to the honeycomb collagen scaffold, differentiated and
      proliferated into osteoblasts. The differentiated osteoblasts were characterized
      by morphological examination and alkaline phosphatase activity. The osteoblasts
      also synthesized calcium-deficient hydroxyapatite (pseudo-hydroxyapatite)
      crystals in the culture. The mineralization was confirmed by Von Kossa staining
      and the crystals were analyzed by X-ray diffraction. Light microscopy and DNA
      measurements showed that the differentiated osteoblasts multiplied into several
      layers on the honeycomb collagen scaffold. The results demonstrated that the
      honeycomb collagen sponge is an excellent scaffold for the differentiation and
      proliferation of mesenchymal stem cells into osteoblasts. The data further proved
      that honeycomb collagen is an effective substrate for tissue engineering
      applications, and is very useful in the advancing field of stem cell technology
      and cell-based therapy.

PMID- 16572436
TI  - Yesterday, today, and tomorrow.

PMID- 16572437
TI  - Extremity magnetic resonance imaging in rheumatoid arthritis: report of the
      American College of Rheumatology Extremity Magnetic Resonance Imaging Task Force.

PMID- 16572438
TI  - Response: office-based low-field extremity magnetic resonance imaging: is the
      glass half empty or half full?

PMID- 16572439
TI  - When is a replication not a replication? Or how to spot a good genetic
      association study.

PMID- 16572440
TI  - Stopping traffic in Sjogren's syndrome.

PMID- 16572441
TI  - Comparison of etanercept and methotrexate, alone and combined, in the treatment
      of rheumatoid arthritis: two-year clinical and radiographic results from the
      TEMPO study, a double-blind, randomized trial.
AB  - OBJECTIVE: To evaluate the efficacy, including radiographic changes, and safety
      of etanercept and methotrexate (MTX), used in combination and alone, in patients
      with rheumatoid arthritis (RA) in whom previous treatment with a disease
      modifying antirheumatic drug other than MTX had failed. METHODS: Patients with RA
      were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to
      20 mg weekly), or combination therapy with etanercept plus MTX through a second
      year, in a double-blinded manner. Clinical response was assessed using American
      College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a
      modified intent-to-treat analysis with the last observation carried forward
      (LOCF) and in a population of completers. Radiographs of the hands, wrists, and
      forefeet were scored for erosions and joint space narrowing at annual intervals.
      RESULTS: A total of 503 of 686 patients continued into year 2 of the study.
      During the 2 years, significantly fewer patients receiving combination therapy
      withdrew from the study (29% of the combination therapy group, 39% of the
      etanercept group, and 48% of the MTX group). Both the LOCF and the completer
      analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and
      ACR70 responses and the remission rates (based on a DAS of <1.6) were
      significantly higher with combination therapy than with either monotherapy
      (P<0.01). Similarly, improvement in disability (based on the Health Assessment
      Questionnaire) was greater with combination therapy (P<0.01). The combination
      therapy group showed significantly less radiographic progression than did either
      group receiving monotherapy (P<0.05); moreover, radiographic progression was
      significantly lower in the etanercept group compared with the MTX group (P<0.05).
      For the second consecutive year, overall disease progression in the combination
      therapy group was negative, with the 95% confidence interval less than zero.
      Adverse events were similar in the 3 treatment groups. CONCLUSION: Etanercept in
      combination with MTX reduced disease activity, slowed radiographic progression,
      and improved function more effectively than did either monotherapy over a 2-year
      period. No increase in toxicity was associated with combination treatment with
      etanercept plus MTX.

PMID- 16572442
TI  - The safety of infliximab, combined with background treatments, among patients
      with rheumatoid arthritis and various comorbidities: a large, randomized, placebo
      controlled trial.
AB  - OBJECTIVE: To assess the risk of serious infections following 22 weeks of
      infliximab therapy, and to further characterize the safety profile of infliximab
      in combination with background treatments during 1 year in patients with
      rheumatoid arthritis (RA) with various comorbidities. METHODS: Patients with
      active RA despite receiving methotrexate (MTX) were randomly assigned to receive
      infusions of placebo (group 1, n=363), 3 mg/kg infliximab (group 2, n=360), or 10
      mg/kg infliximab (group 3, n=361) at weeks 0, 2, 6, and 14. At week 22, patients
      in placebo group 1 began receiving 3 mg/kg infliximab, and patients in group 3
      continued to receive an infliximab dose of 10 mg/kg. Patients in group 2 who
      failed to meet predefined response criteria received increasing doses of
      infliximab in increments of 1.5 mg/kg. RESULTS: At week 22, the relative risk of
      developing serious infections in groups 2 and 3, compared with group 1, was 1.0
      (95% confidence interval [95% CI] 0.3-3.1, P=0.995) and 3.1 (95% CI 1.2-7.9,
      P=0.013), respectively. The incidence of serious adverse events was 7.8% in
      groups 2 and 3 compared with 7.5% in group 1. From week 22 to week 54, 11.8%,
      9.9%, and 10.3% of patients in groups 1, 2, and 3, respectively, reported
      occurrences of serious adverse events. Through week 54, 1 patient in group 1, 2
      patients in group 2, and 4 patients in group 3 developed active tuberculosis.
      CONCLUSION: The risk of serious infections in patients receiving the approved
      infliximab dose of 3 mg/kg plus MTX was similar to that in patients receiving MTX
      alone. Patients receiving the unapproved induction regimen of 10 mg/kg infliximab
      plus MTX followed by a 10 mg/kg maintenance regimen had an increased risk of
      serious infections through week 22.

PMID- 16572443
TI  - Efficacy and toxicity of methotrexate in early rheumatoid arthritis are
      associated with single-nucleotide polymorphisms in genes coding for folate
      pathway enzymes.
AB  - OBJECTIVE: To determine associations of methotrexate (MTX) efficacy and toxicity
      with single-nucleotide polymorphisms (SNPs) in genes coding for folate pathway
      enzymes in patients with early rheumatoid arthritis (RA). METHODS: Patients
      (n=205) with active RA received MTX at an initial dosage of 7.5 mg/week, which
      was increased to 15 mg/week and combined with folic acid (1 mg/day) after 4
      weeks. If the Disease Activity Score in 44 joints (DAS44) was >2.4 at 3 months,
      MTX was increased to 25 mg/week. MTX efficacy was evaluated at 3 and 6 months and
      compared for genotypes in 3 analyses: patients with and without good response
      (DAS44<or=2.4), patients with and without good improvement (DeltaDAS44>1.2), and
      patients with and without moderate improvement (DeltaDAS44>0.6). The association
      between MTX-related adverse drug events (ADEs) and genotype was evaluated by
      comparing genotypes between patients with and without ADEs, specifically
      pneumonitis, gastrointestinal ADEs, skin and mucosal ADEs, and elevated liver
      enzyme levels. The following SNPs were analyzed: methylenetetrahydrofolate
      reductase (MTHFR) 677C>T, MTHFR 1298A>C, dihydrofolate reductase (DHFR) -473G>A,
      DHFR 35289G>A, and reduced folate carrier 80G>A. In case of significant
      differences, odds ratios (ORs) were calculated. RESULTS: At 6 months, MTHFR
      1298AA was associated with good improvement relative to 1298C (OR 2.3, 95%
      confidence interval [95% CI] 1.18-4.41), which increased with increased copies of
      the MTHFR 677CC haplotype. In contrast, MTHFR 1298C allele carriers developed
      more ADEs (OR 2.5, 95% CI 1.32-4.72). CONCLUSION: Patients with MTHFR 1298AA and
      MTHFR 677CC showed greater clinical improvement with MTX, whereas only the MTHFR
      1298C allele was associated with toxicity. In the future, MTHFR genotypes may
      help determine which patients will benefit most from MTX treatment.

PMID- 16572444
TI  - High-resolution multipinhole single-photon-emission computed tomography in
      experimental and human arthritis.
AB  - OBJECTIVE: To image inflammatory arthritic lesions in experimental arthritis and
      in patients with arthritis, using a newly developed high-resolution multipinhole
      single-photon-emission computed tomography (MPH-SPECT) technique. METHODS: Six
      interleukin-1 receptor antagonist-deficient mice with arthritis of the front and
      back paws and 2 control BALB/c mice were imaged with MPH-SPECT and scored
      macroscopically for arthritis. SPECT imaging was performed with a conventional
      gamma camera upgraded with a pyramidal lead collimator affixed with MPH
      apertures. All images were reconstructed, and uptake in the paws was quantified
      in counts/weight and injected activity. To transfer the imaging technique to
      humans we examined the clinically dominant hand of 6 individuals (3 with
      established rheumatoid arthritis [RA], 1 with early RA, 1 with osteoarthritis,
      and 1 healthy control). RESULTS: MPH-SPECT images were high-resolution 3
      dimensional tomographic images, which allowed exact localization and quantifiable
      observation of increased bone metabolism. MPH-SPECT counts of inflamed joints in
      mice correlated with macroscopic scoring and histologic joint analysis
      postmortem. In humans, MPH-SPECT images depicted a detailed visualization of
      tracer accumulation in bony structures of hand and finger joints, and were also
      capable of imaging increased bone metabolism that had appeared normal with other
      imaging modalities, e.g., magnetic resonance imaging. CONCLUSION: The MPH-SPECT
      technique represents a new diagnostic tool in the detection of bone pathology in
      small-animal arthritis research. Compared with macroscopic scoring, this new
      method provides a more objective and higher-precision quantifiable measurement of
      bone reaction, allowing visualization of inflammatory processes of the whole
      skeleton in vivo. These results suggest that MPH-SPECT may be useful as a
      diagnostic instrument for monitoring experimental arthritis, with further
      potential for use in human studies of RA.

PMID- 16572445
TI  - Association of tumor necrosis factor alpha polymorphism, but not the shared
      epitope, with increased radiographic progression in a seropositive rheumatoid
      arthritis inception cohort.
AB  - OBJECTIVE: To determine whether the tumor necrosis factor alpha (TNFA) -308
      guanine-to-adenosine polymorphism and/or the shared epitope (SE) is associated
      with radiographic damage in patients with early rheumatoid arthritis (RA).
      METHODS: The cohort consisted of 189 patients with early seropositive RA (median
      5.6 months since symptom onset) who had active disease, no previous disease
      modifying antirheumatic drug treatment, and >or=2 sets of scored radiographs of
      the hands/wrists and forefeet. TNFA -308 polymorphism was analyzed by polymerase
      chain reaction pyrosequencing. The SE was defined as presence of any 1 of the
      following HLA-DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410,
      *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp
      score. RESULTS: Using a weighted least-squares regression analysis, patients with
      the -308 TNFA AA plus AG genotypes (n=49) had significantly higher rates of
      progression in erosion scores (median 0.84 versus 0.48 units/year), joint space
      narrowing (JSN) scores (0.42 versus 0.04), and total Sharp scores (1.70 versus
      0.61) compared with patients with the TNFA GG genotype (n=140). Presence of the
      SE (n=137) was associated with significantly lower progression rates (per year)
      for total Sharp scores (median 0.9 versus 1.25 units/year) and JSN scores (0.04
      versus 0.41), but not for erosion scores (0.50 versus 0.61) compared with
      patients without the SE (n=52). In a least-squares multiple linear regression
      model, the presence of the AA plus AG genotypes was associated with a
      significantly higher progression rate after adjusting for the presence of the SE,
      interaction between the SE and the AA plus AG genotypes, baseline log C-reactive
      protein level, Health Assessment Questionnaire Disability Index, total Sharp
      score, swollen joint count, and presence of osteophytes (osteoarthritis). There
      was a strong linkage disequilibrium between DRB1*0301 and TNFA polymorphism
      (D'=0.84, r2=0.45, P<0.001). CONCLUSION: This study showed an association between
      the TNFA -308 polymorphism and progression of radiographic damage in patients
      with early seropositive RA. This association appeared to be independent of the
      SE, but might be dependent on other genetic variants in linkage disequilibrium
      with the -308 TNFA A allele and DRB1*0301. Further studies should be conducted to
      validate these results in both longitudinal observational cohorts and randomized
      clinical trials.

PMID- 16572446
TI  - The HLA-DRB1 shared epitope alleles are primarily a risk factor for anti-cyclic
      citrullinated peptide antibodies and are not an independent risk factor for
      development of rheumatoid arthritis.
AB  - OBJECTIVE: The shared epitope (SE)-containing HLA-DRB1 alleles represent the most
      significant genetic risk factor for rheumatoid arthritis (RA). Recent studies
      indicate that the SE alleles are associated with only RA that is characterized by
      the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies, and not
      with anti-CCP-negative disease. In this study we investigated whether the SE
      alleles contribute to the development of anti-CCP-positive RA, or whether they
      are associated solely with the presence of anti-CCP antibodies. We therefore
      determined the influence of the SE alleles and anti-CCP antibodies on the
      progression from recent-onset undifferentiated arthritis (UA) to RA. METHODS:
      Patients with recent-onset UA at the 2-week visit (n=570) were selected from the
      Leiden Early Arthritis Cohort. SE alleles, rheumatoid factor (RF) status, and
      anti-CCP antibody levels were determined. Progression to RA or other diagnoses
      was monitored. RESULTS: One hundred seventy-seven patients with UA developed RA
      during the 1-year followup, whereas the disease in 393 patients remained
      unclassified or was given other diagnoses. The SE alleles correlated with the
      presence of anti-CCP antibodies, but not with the presence of RF. Both in SE
      positive and in SE-negative patients with UA, the presence of anti-CCP antibodies
      was significantly associated with the development of RA. More intriguingly,
      however, no apparent contribution of the SE alleles to the progression to RA was
      found when analyses were stratified according to the presence of anti-CCP
      antibodies. In patients with anti-CCP-positive disease, the presence of SE
      alleles was associated with significantly higher levels of anti-CCP antibodies,
      suggesting that the SE alleles act as classic immune response genes. CONCLUSION:
      The SE alleles do not independently contribute to the progression to RA from UA,
      but rather contribute to the development of anti-CCP antibodies.

PMID- 16572447
TI  - Synovial membrane cytokine expression is predictive of joint damage progression
      in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort).
AB  - OBJECTIVE: The primary aim of this prospective 2-year study was to explain the
      wide variability in joint damage progression in patients with rheumatoid
      arthritis (RA) from measures of pathologic changes in the synovial membrane.
      METHODS: Patients underwent clinical measurements and joint damage assessments by
      magnetic resonance imaging (MRI) and radiography at enrollment and at year 2.
      Synovial membrane was obtained by knee biopsy and assessed histologically by
      hematoxylin and eosin staining. Interleukin-1beta (IL-1beta), IL-10, IL-16, IL
      17, RANKL, tumor necrosis factor alpha (TNFalpha), and interferon-gamma
      (IFNgamma) messenger RNA (mRNA) expression was determined by quantitative reverse
      transcription-polymerase chain reaction. The relationship of synovial
      measurements to joint damage progression was determined by multivariate analysis.
      RESULTS: Sixty patients were enrolled. Histologic features had no relationship to
      damage progression. Multivariate analysis by several different methods
      consistently demonstrated that synovial membrane mRNA levels of IL-1beta,
      TNFalpha, IL-17, and IL-10 were predictive of damage progression. IL-17 was
      synergistic with TNFalpha. TNFalpha and IL-17 effects were most pronounced with
      shorter disease duration, and IL-1beta effects were most pronounced with longer
      disease duration. IFNgamma was protective. These factors explained 57% of the MRI
      joint damage progression over 2 years. CONCLUSION: We have demonstrated for the
      first time in a prospective study that synovial membrane cytokine mRNA expression
      is predictive of joint damage progression in RA. The findings for IL-1beta and
      TNFalpha are consistent with results of previous clinical research, but the
      protective role of IFNgamma, the differing effects of disease duration, and IL-17
      cytokine interactions had only been demonstrated previously by animal and in
      vitro research. These findings explain some of the variability of joint damage in
      RA and identify new targets for therapy.

PMID- 16572448
TI  - Regulatory role of heme oxygenase 1 in inflammation of rheumatoid arthritis.
AB  - OBJECTIVE: To examine the expression and pathogenetic roles of heme oxygenase 1
      (HO-1), an inducible heme-degrading enzyme with antiinflammatory properties, in
      rheumatoid arthritis (RA). METHODS: HO-1 expression in synovial tissue from
      patients with RA, patients with osteoarthritis, and patients with noninflammatory
      joint diseases was determined by immunoblotting and immunohistochemistry. Effects
      of various agents, such as hemin (a chemical inducer of HO-1), small interfering
      RNA (siRNA) specific for HO-1, HO-1 expression vector, and antirheumatic agents,
      on HO-1 expression in RA synovial cell lines were analyzed by real-time reverse
      transcription-polymerase chain reaction (PCR) and immunoblotting. Cytokine
      synthesis was evaluated by real-time PCR and enzyme-linked immunosorbent assay.
      RESULTS: HO-1 was expressed more abundantly in the lesions of synovial tissue
      from patients with RA than in those from the other patient groups. Hemin,
      auranofin, and HO-1 expression vector induced HO-1 and reduced expression of
      tumor necrosis factor alpha (TNFalpha) messenger RNA, lipopolysaccharide (LPS)
      induced secretion of interleukin-6 (IL-6) and IL-8, and expression of
      cyclooxygenase 2 in the synovial cell lines. Treatment with HO-1-specific siRNA
      augmented the synthesis of TNFalpha, IL-6, and IL-8 and canceled the suppressive
      effects of auranofin on TNFalpha secretion. When hemoglobin, as a scavenger of
      carbon monoxide, was added to auranofin-treated synovial cell lines, LPS
      dependent production of IL-6 and IL-8 was increased. CONCLUSION: Our data
      demonstrate that HO-1 is expressed in RA synovial tissues and plays a regulatory
      role in the development of inflammation. The pharmacologic effects of auranofin
      depend, in part, on the levels of HO-1, suggesting that HO-1 induction is a novel
      therapeutic strategy for RA.

PMID- 16572449
TI  - Evaluation of classical complement pathway activation in rheumatoid arthritis:
      measurement of C1q-C4 complexes as novel activation products.
AB  - OBJECTIVE: Novel activation products that are stable and minimally susceptible to
      in vitro artefacts have recently been described in the classical complement
      pathway. The present study assessed circulating levels of these products, i.e.,
      covalent complexes between the recognition molecule of the classical pathway
      (C1q) and activated C4, in plasma samples from patients with rheumatoid arthritis
      (RA) to establish the relationship between these levels and the clinical and
      immunologic parameters in these patients. METHODS: C1q-C4 levels were measured in
      plasma samples from 41 patients with active RA and 43 patients with inactive RA.
      These levels were related to other complement activation products and to disease
      activity according to the Disease Activity Score in 28 joints (DAS28), using
      Spearman's rank correlations. RESULTS: C1q-C4 plasma levels were significantly
      higher in patients with active RA as compared with patients with RA in clinical
      remission (median 3.3 arbitrary units [AU], range 0.4-13.4 versus 1.7 AU, range
      0.2-5.5; P=0.0001), suggesting that activation of the classical complement
      pathway reflects disease activity. This was supported by a significant
      correlation between C1q-C4 levels and the DAS28 (r=0.398, P=0.0002). Levels of
      other complement activation products, such as activated C4 (C4b/c), were also
      significantly elevated in patients with active disease compared with patients
      with inactive disease (P=0.03), and were correlated with C1q-C4 levels (r=0.329,
      P=0.002). Levels of C1q-C4 complexes were higher in synovial fluid samples than
      in plasma samples from the 4 patients tested. CONCLUSION: Systemic complement
      activation via the classical pathway in patients with RA correlates with disease
      activity. These results indicate that C1q-C4 complexes may be used as a biomarker
      for RA.

PMID- 16572450
TI  - Expanded bed adsorption/desorption of proteins with Streamline Direct CST I
      adsorbent.
AB  - Streamline Direct CST I is a new type of ion exchanger with multi-modal
      functional groups, specially designed for an expanded bed adsorption (EBA)
      process, which can capture directly the proteins from the high ionic strength
      feedstocks with a high binding capacity. In this study, an experimental study is
      carried out for two-component proteins (BSA and myoglobin) competitive adsorption
      and desorption in an expanded bed packed with Streamline Direct CST I. Based on
      the measurements of the single- and two-component bovine serum albumin
      (BSA)/myoglobin adsorption isotherm on Streamline Direct CST I, the binding and
      elution conditions for the whole EBA process are selected; and then frontal
      analysis for a longer timescale and column displacement experiments in a fixed
      bed (XK16/20 column) are carried out to evaluate the two-component proteins (BSA
      and myoglobin) competitive adsorption and displacement on Streamline Direct CST
      I. Finally, the feasibility of capturing both BSA and myoglobin by an expanded
      bed packed with Streamline Direct CST I is addressed in a Streamline 50 column
      packed with 300 mL Streamline Direct CST I.

PMID- 16572451
TI  - Antimuscarinic antibodies in primary Sjogren's syndrome reversibly inhibit the
      mechanism of fluid secretion by human submandibular salivary acinar cells.
AB  - OBJECTIVE: Sjogren's syndrome (SS) is an autoimmune condition affecting salivary
      glands, for which a clearly defined pathogenic autoantibody has yet to be
      identified. Autoantibodies that bind to the muscarinic M3 receptors (M3R), which
      regulate fluid secretion in salivary glands, have been proposed in this context.
      However, there are no previous data that directly show antisecretory activity.
      This study was undertaken to investigate and characterize the antisecretory
      activity of anti-M3R. METHODS: Microfluorimetric Ca2+ imaging and patch clamp
      electrophysiologic techniques were used to measure the secretagogue-evoked
      increase in [Ca2+]i and consequent activation of Ca2+-dependent ion channels in
      individual mouse and human submandibular acinar cells. Together, these techniques
      form a sensitive bioassay that was used to determine whether IgG isolated from
      patients with primary SS and from control subjects has antisecretory activity.
      RESULTS: IgG (2 mg/ml) from patients with primary SS reduced the carbachol-evoked
      increase in [Ca2+]i in both mouse and human acinar cells by approximately 50%.
      IgG from control subjects had no effect on the Ca2+ signal. Furthermore, the
      inhibitory action of primary SS patient IgG on the Ca2+ signal was acutely
      reversible. We repeated our observations using rabbit serum containing antibodies
      raised against the second extracellular loop of M3R and found an identical
      pattern of acutely reversible inhibition. Anti-M3R-positive serum had no effect
      on Ca2+-dependent ion channel activation evoked by the direct intracellular
      infusion of inositol 1,4,5-triphosphate. CONCLUSION: These observations show for
      the first time that IgG from patients with primary SS contains autoantibodies
      capable of damaging saliva production and contributing to xerostomia. The unusual
      but not unprecedented acute reversibility of the effects of anti-M3
      autoantibodies is the subject of further research.

PMID- 16572452
TI  - Monitoring the stability of crosslinked protein crystals biotemplates: a
      feasibility study.
AB  - Protein crystals, routinely prepared for the elucidation of protein 3D structures
      by X-ray crystallography, present an ordered and highly accurate 3D array of
      protein molecules. Inherent to the 3D arrangement of the protein molecules in the
      crystal is a complementary 3D array of voids made of interconnected cavities and
      exhibiting highly ordered porosity. The permeability of the porosity of
      chemically crosslinked enzyme protein crystals to low molecular weight solutes,
      was used for enzyme mediated organic synthesis and size exclusion chromatography.
      This permeability might be extended to explore new potential applications for
      protein crystals, for example, their use as bio-templates for the fabrication of
      novel, nano-structured composite materials. The quality of composites obtained
      from "filling" of the ordered voids in protein crystals and their potential
      applications will be strongly dependent upon an accurate preservation of the
      order in the original protein crystal 3D array during the "filling" process. Here
      we propose and demonstrate the feasibility of monitoring the changes in 3D order
      of the protein array by a step-by-step molecular level monitoring of a model
      system for hydrogel bio-templating by glutaraldehyde crosslinked lysozyme
      crystals. This monitoring is based on step-by-step comparative analysis of data
      obtained from (i) X-ray crystallography: resolution, unit cell dimensions and B
      factor values and (ii) fluorescence decay kinetics of ultra-fast laser activated
      dye, impregnated within these crystals. Our results demonstrated feasibility of
      the proposed monitoring approach and confirmed that the stabilized protein
      crystal template retained its 3D structure throughout the process.

PMID- 16572453
TI  - Intraarticular induction of interleukin-1beta expression in the adult mouse, with
      resultant temporomandibular joint pathologic changes, dysfunction, and pain.
AB  - OBJECTIVE: To examine the effects of intraarticular induction of interleukin
      1beta (IL-1beta) expression in adult mice. METHODS: We used somatic mosaic
      analysis in a novel transgenic mouse with an inducible IL-1beta transcription
      unit. Transgene activation was induced by Cre recombinase in the
      temporomandibular joints (TMJs) of adult transgenic mice (conditional knockin
      model). The effects of intraarticular IL-1beta induction were subsequently
      evaluated at the cellular, histopathologic, and behavioral levels. RESULTS: We
      developed transgenic mice capable of germline transmission of a dormant
      transcription unit consisting of the mature form of human IL-1beta as well as the
      reporter gene beta-galactosidase driven by the rat procollagen 1A1 promoter.
      Transgene activation by a feline immunodeficiency virus Cre vector resulted in
      histopathologic changes, including articular surface fibrillations, cartilage
      remodeling, and chondrocyte cloning. We also demonstrated up-regulation of genes
      implicated in arthritis (cyclooxygenase 2, IL-6, matrix metalloproteinase 9).
      There was a lack of inflammatory cells in these joints. Behavioral changes,
      including increased orofacial grooming and decreased resistance to mouth opening,
      were used as measures of nociception and joint dysfunction, respectively. The
      significant increase in expression of the pain-related neurotransmitter
      calcitonin gene-related peptide (CGRP) in the sensory ganglia as well as the
      auxiliary protein CGRP receptor component protein of the calcitonin-like receptor
      in the brainstem further substantiated the induction of pain. CONCLUSION:
      Induction of IL-1beta expression in the TMJs of adult mice led to pathologic
      development, dysfunction, and related pain in the joints. The somatic mosaic
      model presented herein may prove useful in the preclinical evaluation of existing
      and new treatments for the management of joint pathologic changes and pain, such
      as in osteoarthritis.

PMID- 16572454
TI  - Potent induction of chondrocytic differentiation of human adipose-derived adult
      stem cells by bone morphogenetic protein 6.
AB  - OBJECTIVE: Recent studies have identified an abundant source of multipotent
      progenitor cells in subcutaneous human adipose tissue, termed human adipose
      derived adult stem cells (ADAS cells). In response to specific media
      formulations, including transforming growth factor beta1 (TGFbeta1), these cells
      exhibit significant ability to differentiate into a chondrocyte-like phenotype,
      expressing cartilage-specific genes and proteins such as aggrecan and type II
      collagen. However, the influence of other growth factors on the chondrogenic
      differentiation of ADAS cells is not fully understood. This study was undertaken
      to investigate the effects of TGFbeta1, TGFbeta3, insulin-like growth factor 1,
      bone morphogenetic protein 6 (BMP-6), and dexamethasone, in various combinations,
      on the chondrogenic potential of ADAS cells in alginate beads. METHODS: The
      chondrogenic response of alginate-encapsulated ADAS cells was measured by
      quantitative polymerase chain reaction, 3H-proline and 35S-sulfate incorporation,
      and immunolabeling for specific extracellular matrix components. RESULTS:
      Significant differences in chondrogenesis were observed under the different
      culture conditions for all outcomes measured. Most notably, BMP-6 up-regulated
      AGC1 and COL2A1 expression by an average of 205-fold and 38-fold, respectively,
      over day-0 controls, while down-regulating COL10A1 expression by approximately 2
      fold. CONCLUSION: These findings suggest that BMP-6 is a potent inducer of
      chondrogenesis in ADAS cells, in contrast to mesenchymal stem cells, which
      exhibit increased expression of type X collagen and a hypertrophic phenotype in
      response to BMP-6. Combinations of growth factors containing BMP-6 may provide a
      novel means of regulating the differentiation of ADAS cells for applications in
      the tissue-engineered repair or regeneration of articular cartilage.

PMID- 16572455
TI  - Refolding strategies for ketosteroid isomerase following insoluble expression in
      Escherichia coli.
AB  - Dilution and column-based protein refolding techniques are compared for refolding
      Delta 5-3-ketosteroid isomerase (KSI) with a C-terminus his6-tag. Column
      refolding was performed by removing the denaturant while the protein was adsorbed
      in an immobilized metal affinity chromatography column. Both dilution refolding
      and a single-step column-based refolding strategy were optimized to maximize the
      recovery of KSI enzyme activity, and achieved refolding yields of 87% and 70%
      respectively. It was found that the column-based refolding yield was reduced at
      higher adsorbed protein concentrations. An elution gradient with increasing
      imidazole concentration was used to selectively elute the biologically active KSI
      protein following column refolding, with high molecular weight KSI aggregates
      retained in the column. An iterative column-refolding process was then developed
      to denature and refold protein retained in the column, which significantly
      increased the refolding yield at high-adsorbed protein concentrations. Repetition
      of the column refolding operation increased the refolding yield from 50% to 75%
      for protein adsorbed at a concentration of 2.9 mg/mL of adsorbent. Although for
      the KSI protein column-based refolding did not improve the overall refolding
      yield compared to dilution refolding, it may still be advantageous due to the
      ease of integration with purification operations, increased control over the
      refolding conditions, and the ability to segregate refolded protein from inactive
      aggregates during elution.

PMID- 16572457
TI  - Activation of the peroxisome proliferator-activated receptor alpha pathway
      potentiates interleukin-1 receptor antagonist production in cytokine-treated
      chondrocytes.
AB  - OBJECTIVE: To determine whether peroxisome proliferator-activated receptor alpha
      (PPARalpha) agonists protect chondrocytes against the effects of interleukin
      1beta (IL-1beta). METHODS: PPARalpha expression and function in cultured rabbit
      articular chondrocytes were studied by Northern blotting, electrophoretic
      mobility shift assay, and transient expression of a luciferase reporter construct
      bearing the human IL-1 receptor antagonist (Il-1Ra) gene promoter. Chondrocytes
      were incubated in vitro with IL-1beta alone or in combination with CloFibrate
      (CloF) or other PPAR ligands. Proteoglycans were evaluated by 35S-sulfate
      incorporation, matrix metalloproteinase (MMP) levels were assessed by zymography
      and enzyme-linked immunosorbent assay (ELISA), and MMP messenger RNA (mRNA)
      levels were measured by Northern blotting and real-time reverse transcriptase
      polymerase chain reaction. IL-1beta and IL-1Ra soluble contents were measured by
      ELISA. RESULTS: CloF counteracted IL-1beta-induced 35S-proteoglycan degradation,
      gelatinolytic activity, and MMP-1, -3, and -13 mRNA expression. CloF also
      maximized IL-1beta-induced endogenous production of soluble IL-1Ra (sIL-1Ra).
      This stimulating effect on IL-1Ra gene expression was shown, by transient
      expression assay, to be transcriptional. Inhibition of sIL-1Ra expression by a
      specific small interfering RNA suppressed the effect of CloF on IL-1beta-induced
      MMP expression. The stimulatory effect of CloF was enhanced by cotransfection
      with wild-type PPARalpha and abolished by a dominant-negative PPARalpha mutant.
      Fenofibrate and WY-14643 displayed a similar stimulating effect on the IL-1Ra
      promoter, while rosiglitazone did not. Two PPAR response elements, an NF-kappaB
      binding site, and a CCAAT/enhancer binding protein-binding site were identified
      in the IL-1Ra promoter. All 4 sites were necessary for mediation of the effects
      of CloF. CONCLUSION: Our findings support the notion that there is a PPARalpha
      dependent mechanism that inhibits IL-1beta function in chondrocytes, which
      operates via an increase in sIL-1Ra production.

PMID- 16572456
TI  - Vesicular glutamate (VGlut), GABA (VGAT), and acetylcholine (VACht) transporters
      in basal forebrain axon terminals innervating the lateral hypothalamus.
AB  - The basal forebrain (BF) is known to play important roles in cortical activation
      and sleep, which are likely mediated by chemically differentiated cell groups
      including cholinergic, gamma-aminobutyric acid (GABA)ergic and other unidentified
      neurons. One important target of these cells is the lateral hypothalamus (LH),
      which is critical for arousal and the maintenance of wakefulness. To determine
      whether chemically specific BF neurons provide an innervation to the LH, we
      employed anterograde transport of 10,000 MW biotinylated dextran amine (BDA)
      together with immunohistochemical staining of the vesicular transporter proteins
      (VTPs) for glutamate (VGluT1, -2, and -3), GABA (VGAT), or acetylcholine (ACh,
      VAChT). In addition, we applied triple staining for the postsynaptic proteins
      (PSPs), PSD-95 with VGluT or Gephyrin (Geph) with VGAT, to examine whether the
      BDA-labeled varicosities may form excitatory or inhibitory synapses in the LH.
      Axons originating from BDA-labeled neurons in the magnocellular preoptic nucleus
      (MCPO) and substantia innominata (SI) descended within the medial forebrain
      bundle and extended collateral varicose fibers to contact LH neurons. In the LH,
      the BDA-labeled varicosities were immunopositive (+) for VAChT ( approximately
      10%), VGluT2 ( approximately 25%), or VGAT ( approximately 50%), revealing an
      important influence of newly identified glutamatergic together with GABAergic BF
      inputs. Moreover, in confocal microscopy, VGluT2+ and VGAT+ terminals were
      apposed to PSD-95+ and Geph+ profiles respectively, indicating that they formed
      synaptic contacts with LH neurons. The important inputs from glutamatergic and
      GABAergic BF cells could thus regulate LH neurons in an opposing manner to
      stimulate vs. suppress cortical activation and behavioral arousal reciprocally.

PMID- 16572458
TI  - Frizzled-related protein variants are risk factors for hip osteoarthritis.
AB  - OBJECTIVE: To examine the association of the Arg200Trp and Arg324Gly variants of
      FRZB with the risk and phenotype of radiographic osteoarthritis (OA) of the hip
      and serum levels of Frizzled-related protein (FRP) in a prospective cohort of
      elderly Caucasian women. METHODS: Radiographic hip OA status of patients was
      defined by the presence of severe joint space narrowing (JSN) (feature
      grade>or=3), a summary grade>or=3, or definite osteophytes (grade>or=2) and JSN
      (grade>or=2) in the same hip. Genotypes were obtained in 569 patients with
      radiographic OA of the hip and in 1,317 and 4,136 controls for the Arg200Trp and
      Arg324Gly variants, respectively. Serum FRP levels were measured by enzyme-linked
      immunosorbent assay. Multivariate logistic regression was performed. RESULTS: The
      minor allele frequency for the Arg200Trp polymorphism was 0.12 in the control
      group compared with 0.14 in the group with radiographic OA of the hip (P=0.12),
      and the minor allele frequency for the Arg324Gly variant was 0.083 in the control
      group compared with 0.088 in the group with radiographic OA of the hip (P=0.63).
      The multilocus genotypes available in 1,886 subjects suggested that inheritance
      of both minor alleles was a risk factor for developing OA characterized by JSN
      (P<0.01). Patients with radiographic OA of the hip who were homozygous for the
      Arg200Trp minor allele had higher serum FRP levels than controls who were
      homozygous for the major allele. CONCLUSION: Our data confirm findings of another
      study, that a rare haplotype with both Arg200Trp and Arg324Gly FRZB variants
      contributes to the genetic susceptibility to hip OA among Caucasian women, and
      that these polymorphisms may contribute to increased serum levels of proteins as
      biomarkers of OA.

PMID- 16572459
TI  - Localization and characterization of pituitary adenylate cyclase-activating
      polypeptide receptors in the human cerebellum during development.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are actively
      expressed in the cortical layers of the cerebellum of rodents and contribute to
      cerebellar development. The present report provides the first anatomical
      localization and characterization of PACAP receptors in the developing human
      cerebellum. RT-PCR analysis from 15-week-old fetuses to 22-year-old subject
      showed that PAC1-R and VPAC1-R are expressed in the cerebellum at all stages,
      whereas VPAC2-R mRNA was barely detectable. In situ hybridization labeling
      indicated that, in human fetuses, PAC1-R mRNA is associated with the external
      granule cell layer (EGL), a germinative neuroepithelium, and with the internal
      granule cell layer (IGL). The distribution pattern of VPAC1-R mRNA was very
      similar to that of PAC1-R mRNA, whereas VPAC2-R mRNA was visualized only in 7-22
      year-old subjects. The localization of [(125)I]PACAP27 binding sites was fully
      consistent with the distribution of PAC1-R and VPAC1-R mRNA. Pharmacological
      characterization revealed that, in the EGL and IGL from 15-24-week-old fetuses
      and in the granule cell layer from 7-22-year-old patients, binding sites exhibit
      a PAC1-R profile. In contrast, PACAP binding sites observed in the molecular
      layer and medulla of the adult cerebellum consisted of a heterogeneous population
      of PAC1-R and VPAC(1/2)-R. Altogether, these data provide the first evidence that
      PACAP receptors are expressed in the human cerebellar cortex. PAC1-R is the
      predominant PACAP receptor found in fetuses, and both PAC1-R and VPAC1-R are
      expressed in the mature cerebellum. These observations suggest that PACAP has
      neurodevelopmental functions in the human cerebellum.

PMID- 16572460
TI  - Low vitamin K status is associated with osteoarthritis in the hand and knee.
AB  - OBJECTIVE: Poor intake of vitamin K is common. Insufficient vitamin K can result
      in abnormal cartilage and bone mineralization. Furthermore, osteophyte growth,
      seen in osteoarthritis (OA), may be a vitamin K-dependent process. We undertook
      this study to determine whether vitamin K deficiency is associated with
      radiographic features of OA. METHODS: We conducted an analysis among 672
      participants (mean age 65.6 years, 358 women) in the Framingham Offspring Study,
      a population-based prospective observational cohort. Levels of plasma
      phylloquinone (the primary form of vitamin K) had previously been measured in
      these participants, for whom we also had bilateral hand and knee radiographs. The
      main outcomes were 1) prevalence ratios (PRs) of OA, osteophytes, and joint space
      narrowing (JSN) per quartile of plasma phylloquinone level for each joint,
      adjusting for correlated joints using generalized estimating equations, and 2)
      adjusted mean number of joints with each feature per quartile of plasma
      phylloquinone level. Analyses were conducted in hands and knees separately and
      adjusted for age, sex, body mass index, total energy intake, plasma vitamin D,
      and femoral neck bone mineral density. RESULTS: The PRs for OA, osteophytes, and
      JSN and adjusted mean number of joints with all 3 features in the hand decreased
      significantly with increasing plasma phylloquinone levels (P<or=0.03 for all).
      For example, as plasma phylloquinone levels rose, the PR for hand OA decreased
      from 1.0 to 0.7 (P=0.005). For the knee, only the PR for osteophytes and the
      adjusted mean number of knee joints with osteophytes decreased significantly with
      increasing plasma phylloquinone levels (PR decreased from 1.0 to 0.6, P=0.01).
      CONCLUSION: These observational data support the hypothesis of an association
      between low plasma levels of vitamin K and increased prevalence of OA
      manifestations in the hand and knee.

PMID- 16572461
TI  - Disc space narrowing as a new risk factor for vertebral fracture: the OFELY
      study.
AB  - OBJECTIVE: In a previous cross-sectional analysis, we found a positive
      association between disc space narrowing (DSN) and vertebral fracture. The aim of
      the present study was to analyze prospectively the risk of vertebral and
      nonvertebral fractures in women with spine osteoarthritis (OA). METHODS: Using
      radiographs, spine OA was evaluated in 634 postmenopausal women from the OFELY
      (Os des Femmes de Lyon) cohort (mean+/-SD age 61.2+/-9 years). Prevalence and
      severity of spine OA were assessed by scoring osteophytes and DSN. Incidental
      clinical fractures were prospectively registered during annual followup, and
      vertebral fractures were evaluated by radiography every 4 years. RESULTS: During
      an 11-year followup, fractures occurred in 121 women, including 42 with vertebral
      fractures. No association was found between osteophytes and the risk of fracture.
      In contrast, DSN was associated with an increased risk of vertebral fractures but
      not of nonvertebral fractures. After adjusting for confounding variables, the
      presence of DSN was associated with a marked increased risk of vertebral
      fractures, with an odds ratio of 6.59 (95% confidence interval 1.36-31.9). In
      addition, 95% of incident vertebral fractures were located above the disc with
      the most severe narrowing. CONCLUSION: This longitudinal study shows that,
      despite a higher bone mineral density (BMD), women with spine OA do not have a
      reduced risk of fracture and that DSN is significantly associated with vertebral
      fracture risk. The location of DSN and of incident vertebral fractures suggests
      that disc degeneration impairs the biomechanics of the above spine, which leads
      to the increased risk of vertebral fractures, independent of BMD. We suggest that
      DSN is a newly identified risk factor for vertebral fracture that should be taken
      into consideration when assessing vertebral fracture risk in postmenopausal
      women.

PMID- 16572462
TI  - Characterization of glucagon-expressing neurons in the chicken retina.
AB  - We recently identified large glucagon-expressing neurons that densely ramify
      neurites in the peripheral edge of the retina and regulate the proliferation of
      progenitors in the circumferential marginal zone (CMZ) of the postnatal chicken
      eye (Fischer et al. [2005] J Neurosci 25:10157-10166). However, nothing is known
      about the transmitters and proteins that are expressed by the glucagon-expressing
      neurons in the avian retina. We used antibodies to cell-distinguishing markers to
      better characterize the different types of glucagon-expressing neurons. We found
      that the large glucagon-expressing neurons were immunoreactive for substance P,
      neurofilament, Pax6, AP2alpha, HuD, calretinin, trkB, and trkC. Colocalization of
      glucagon and substance P in the large glucagon-expressing neurons indicates that
      these cells are the "bullwhip cells" that have been briefly described by Ehrlich
      et al. ([1987] J Comp Neurol 266:220-233). Similar to the bullwhip cells, the
      conventional glucagon-expressing amacrine cells were immunoreactive for
      calretinin, HuD, Pax6, and AP2alpha. Unlike bullwhip cells, the conventional
      glucagon-expressing amacrine cells were immunoreactive for GABA. While glucagon
      immunoreactive amacrine cells were negative for substance P in central regions of
      the retina, a subset of this type of amacrine cell was immunoreactive for
      substance P in far peripheral regions of the retina. An additional type of
      glucagon/substance P-expressing neuron, resembling the bullwhip cells, was found
      in far peripheral and dorsal regions of the retina. Based on morphology,
      distribution within the retina, and histological markers, we conclude that there
      may be four different types of glucagon-expressing neurons in the avian retina.

PMID- 16572463
TI  - Development of callosal topography in visual cortex of normal and enucleated
      rats.
AB  - In normal rats callosal projections in striate cortex connect retinotopically
      corresponding, nonmirror-symmetric cortical loci, whereas in rats bilaterally
      enucleated at birth, callosal fibers connect topographically mismatched, mirror
      symmetric loci. Moreover, retina input specifies the topography of callosal
      projections by postnatal day (P)6. To investigate whether retinal input guides
      development of callosal maps by promoting either the corrective pruning of
      exuberant axon branches or the specific ingrowth and elaboration of axon branches
      at topographically correct places, we studied the topography of emerging callosal
      connections at and immediately after P6. After restricted intracortical
      injections of anterogradely and retrogradely transported tracers we observed that
      the normal, nonmirror-symmetric callosal map, as well as the anomalous, mirror
      symmetric map observed in neonatally enucleated animals, are present by P6-7,
      just as collateral branches of simple architecture emerge from their parental
      axons and grow into superficial cortical layers. Our results therefore do not
      support the idea that retinal input guides callosal map formation by primarily
      promoting the large-scale elimination of long, nontopographic branches and
      arbors. Instead, they suggest that retinal input specifies the sites on the
      parental axons from which interstitial branches will grow to invade middle and
      upper cortical layers, thereby ensuring that the location of invading
      interstitial branches is accurately related to the topographical location of the
      soma that gives rise to the parental axon. Moreover, our results from enucleated
      rats suggest that the cues that determine the mirror-symmetric callosal map exert
      only a weak control on the topography of fiber ingrowth.

PMID- 16572464
TI  - Organization of pontocerebellar projections to identified climbing fiber zones in
      the rat.
AB  - The organization of pontocerebellar projections to the paravermis and hemisphere
      of the posterior cerebellum of the rat was studied in relation to the
      organization of climbing fibers. Small injections of cholera toxin subunit B were
      placed in the cerebellar cortex at locations predetermined by evoked climbing
      fiber potentials from selected body parts or based on coordinates. The injection
      site was characterized with respect to the zebrin pattern and by the distribution
      of retrogradely labeled neurons in the inferior olive. The following zones were
      studied: hindlimb-related zones C1 and C2 of lobule VIII; forelimb-related zones
      C1, C2, and D0/D1 of the paramedian lobule; and face-related zones A2 of the
      paramedian lobule and C2 and D0 of crus 2B. The results show that the
      distribution of pontine neurons is closely related to the climbing fiber
      somatotopy. Injections centered on face-related zones result in distribution of
      pontine neurons within the pontine core region. Forelimb regions surround this
      core, whereas hindlimb regions are mostly supplied by caudal pontine regions and
      by a single patch of more rostrally located neurons. This distribution fits well
      with published data on the somatotopy of the corticopontine projection from the
      rat primary somatosensory cortex. However, apart from differences in the
      participation of ipsilaterally projecting cells, the distribution of pontine
      neurons does not change significantly when the injection covers different zones
      of the same lobule such as C1 and C2 of lobule VIII; C1, C2, and D0/D1 of the
      paramedian lobule; A2 of the paramedian lobule; and C2 and D0 of crus 2B.

PMID- 16572465
TI  - Production of cloned goats by nuclear transfer of cumulus cells and long-term
      cultured fetal fibroblast cells into abattoir-derived oocytes.
AB  - Dairy goats are ideal for the transgenic production of therapeutic recombinant
      proteins. The use of recombinant somatic cell lines for nuclear transfer (NT)
      allows the introduction of genes by transfection, increases the efficiency of
      transgenic animal production to 100%, and overcomes the problem of founder
      mosaicism. Although viable animals have been cloned via NT from somatic cells of
      11 species, the efficiency has been extremely low. Both blastomere and somatic
      cell NT increased fetal loss and perinatal morbidity/mortality in cattle and
      sheep, but fetal loss and perinatal mortality appear to be relatively low in
      goats. In this study, we produced cloned goats by NT from cumulus cells and long
      term cultured fetal fibroblast cells (FFCs) to abattoir-derived oocytes. NT
      embryos were constructed from electrofusion of cumulus cells (CCs), FFCs, or skin
      fibroblast cells (SFCs) with cytoplasts prepared from abattoir-derived ovaries.
      The NT embryos were activated with an optimized activating protocol (1 min
      exposure to 2.5 microM ionomycin followed by 2 hr incubation in 2mM 6-DMAP). Two
      viable cloned kids from CCs and one from long-term cultured FFCs (at passage 20
      25) were born. Microsatellite analysis of 10 markers confirmed that all cloned
      offspring were derived from corresponding donor cells. To our knowledge, the
      production of cloned goat offspring using abattoir-derived oocytes receiving
      nuclei from CCs and long-term cultured FFCs has not been reported. The production
      of viable cloned animals after activation with reduced intensity of ionomycin and
      6-DMAP treatment has also not been reported. Loss of cloned embryos was obvious
      after 45 and 90 days of pregnancy, and a lack of cotyledons, heart defects, and
      improperly closed abdominal wall were observed in the aborted fetuses and one
      cloned kid. The fusibility and in vitro developmental potential of embryos
      reconstructed from FFCs at passage 20-25 were significantly lower than those of
      embryos reconstructed from FFCs at passage 3-5, and the cloning efficiency of the
      long-term cultured cells was low (0.5%).

PMID- 16572466
TI  - Synaptotagmin I is involved in the regulation of cortical granule exocytosis in
      the sea urchin.
AB  - Cortical granules are stimulus-dependent secretory vesicles found in the egg
      cortex of most vertebrates and many invertebrates. Upon fertilization, an
      increase in intracellular calcium levels triggers cortical granules to exocytose
      enzymes and structural proteins that permanently modify the extracellular surface
      of the egg to prevent polyspermy. Synaptotagmin is postulated to be a calcium
      sensor important for stimulus-dependent secretion and to test this hypothesis for
      cortical granule exocytosis, we identified the ortholog in two sea urchin species
      that is present selectively on cortical granules. Characterization by RT-PCR, in
      situ RNA hybridization, Western blot and immunolocalization shows that
      synaptotagmin I is expressed in a manner consistent with it having a role during
      cortical granule secretion. We specifically tested synaptotagmin function during
      cortical granule exocytosis using a microinjected antibody raised against the
      entire cytoplasmic domain of sea urchin synaptotagmin I. The results show that
      synaptotagmin I is essential for normal cortical granule dynamics at
      fertilization in the sea urchin egg. Identification of this same protein in other
      developmental stages also shown here will be important for interpreting stimulus
      dependent secretory events for signaling throughout embryogenesis.

PMID- 16572467
TI  - Detection of 28 neurotransmitters and related compounds in biological fluids by
      liquid chromatography/tandem mass spectrometry.
AB  - This work presents two liquid chromatography/tandem mass spectrometry (LC/MS/MS)
      acquisition modes: multiple reaction monitoring (MRM) and neutral loss scan (NL),
      for the analysis of 28 compounds in a mixture. This mixture includes 21 compounds
      related to the metabolism of three amino acids: tyrosine, tryptophan and glutamic
      acid, two pterins and five deuterated compounds used as internal standards. The
      identification of compounds is achieved using the retention times (RT) and the
      characteristic fragmentations of ionized compounds. The acquisition modes used
      for the detection of characteristic ions turned out to be complementary: the
      identification of expected compounds only is feasible by MRM while expected and
      unexpected compounds are detected by NL. In the first part of this work, the
      fragmentations characterizing each molecule of interest are described. These
      fragmentations are used in the second part for the detection by MRM and NL of
      selected compounds in mixture with and without biological fluids. Any preliminary
      extraction precedes the analysis of compounds in biological fluids.

PMID- 16572468
TI  - Identification of proteins in excretory/secretory extracts of Echinostoma friedi
      (Trematoda) from chronic and acute infections.
AB  - In the present study, we describe the investigation of Echinostoma friedi
      excretory/secretory products using a proteomic approach combined with the use of
      heterologous antibodies. We have identified 18 protein spots corresponding to ten
      proteins, including cytoskeletal proteins like actin, tropomyosin, and
      paramyosin; glycolytic enzymes like enolase, glyceraldehyde 3P dehydrogenase, and
      aldolase; detoxifying enzymes like GSTs; and stress proteins like heat shock
      protein (Hsp) 70. Among these proteins, both actin and, to a lesser extent,
      Hsp70, exhibited differential expression patterns between chronic and acute
      infections in the Echinostoma-rodent model, suggesting that these proteins may
      play a role in the survival within the host.

PMID- 16572469
TI  - Antibodies for proteomic research: comparison of traditional immunization with
      recombinant antibody technology.
AB  - Antibodies play a pivotal role in studying the expression and function of
      proteins. Proteomics studies require the generation of specific and high-affinity
      antibodies against large numbers of proteins. While traditional animal-based
      antibody generation is laborious, difficult to automate, and therefore less
      suited to keep up with the requirements of proteomics research, the use of
      recombinant in vitro antibody technology might offer a solution to this problem.
      However, it has not been demonstrated yet that such antibodies are at least as
      useful as conventional antibodies for typical proteomics applications. Here we
      generated novel recombinant Fab antibody fragments from the naive HuCAL GOLD
      library against a number of targets derived from a mouse cDNA library. We
      compared these antibodies with polyclonal antisera produced against the same
      targets and show that these recombinant antibodies are useful reagents for
      typical applications like Western blotting or immunohistochemistry.

PMID- 16572470
TI  - Proteome analysis of salt stress response in the cyanobacterium Synechocystis sp.
      strain PCC 6803.
AB  - In the present study, changes in protein synthesis patterns after salt shock
      visualized by 35S-methionine labeling and the changed protein composition in salt
      acclimated cells of the cyanobacterium Synechocystis sp. strain PCC 6803 were
      analyzed by a combination of 2-DE for protein separation and PMF for protein
      identification. As a basis for the differential analysis, a proteome map with 500
      identified protein spots comprising 337 different protein species was
      established. Fifty-five proteins were found, which are induced by salt shock or
      accumulated after long-term salt acclimation. Some of the proteins are salt
      stress-specific, such as enzymes involved in the synthesis of the compatible
      solute glucosylglycerol, while most of them are involved in general stress
      acclimation. Particularly, heat-shock proteins and proteins acting against
      lesions by reactive oxygen species were found. Moreover, changes in enzymes
      involved in basic carbohydrate metabolism were detected. The dynamic of the
      proteome of salt-stressed Synechocystis cells was compared to previous data
      concerning transcriptome analysis revealing that 89% of the proteins induced
      shortly after salt shock were also found to be induced at the RNA level. However,
      42% of the stably up-regulated proteins in salt-acclimated cells were not
      detected previously using DNA microarrays. The comparison of transcriptomic and
      proteomic analyses shows the significance of post-transcriptional regulatory
      mechanisms in acclimation of Synechocystis to high salt concentrations.

PMID- 16572471
TI  - Proteomic investigation in the detection of the illicit treatment of calves with
      growth-promoting agents.
AB  - The use of beta-agonists, sexual steroids, and corticosteroids as growth
      promoting agents (GPAs) in veal calves is forbidden in the European Union (EU)
      and subjected to restrictions in the US because it may be potentially noxious for
      both treated animals and the consumer. Although official controls performed in
      the EU have revealed a limited number of positive samples, the analysis of seized
      preparations indicate that the use of illegal GPAs is far from being abandoned.
      The presence of these compounds in matrixes of biological origin often goes
      unnoticed because of the use of very low dosages and/or of molecules of unknown
      chemical structure. It is therefore necessary to develop screening methods based
      on the biological effects of these substances that allow the simultaneous
      screening of many components, as proteome analysis. When hepatic cytosols and
      microsomes from calves treated with a combination of GPAs were analyzed by 2-DE,
      we found changes in the expression of two proteins, which we identified as
      adenosine kinase and reticulocalbin. Our aim was not to speculate about molecular
      mechanisms, but to show the ability of the proteomic approach to find biomarkers
      of illicit treatments and to use it as a basis to develop large-scale screening
      methods.

PMID- 16572472
TI  - CO2 limitation induces specific redox-dependent protein phosphorylation in
      Chlamydomonas reinhardtii.
AB  - Acclimation of the green alga Chlamydomonas reinhardtii to limiting environmental
      CO2 induced specific protein phosphorylation at the surface of photosynthetic
      thylakoid membranes. Four phosphopeptides were identified and sequenced by
      nanospray quadrupole TOF MS from the cells acclimating to limiting CO2. One
      phosphopeptide originated from a protein that has not been annotated. We found
      that this unknown expressed protein (UEP) was encoded in the genome of C.
      reinhardtii. Three other phosphorylated peptides belonged to Lci5 protein encoded
      by the low-CO2-inducible gene 5 (lci5). The phosphorylation sites were mapped in
      the tandem repeats of Lci5 ensuring phosphorylation of four serine and three
      threonine residues in the protein. Immunoblotting with Lci5-specific antibodies
      revealed that Lci5 was localized in chloroplast and confined to the stromal side
      of the thylakoid membranes. Phosphorylation of Lci5 and UEP occurred strictly at
      limiting CO2; it required reduction of electron carriers in the thylakoid
      membrane, but was not induced by light. Both proteins were phosphorylated in the
      low-CO2-exposed algal mutant deficient in the light-activated protein kinase
      Stt7. Phosphorylation of previously unknown basic proteins UEP and Lci5 by
      specific redox-dependent protein kinase(s) in the photosynthetic membranes
      reveals the early response of green algae to limitation in the environmental
      inorganic carbon.

PMID- 16572473
TI  - Analysis of the cerebellar proteome in a transgenic mouse model of inherited
      prion disease reveals preclinical alteration of calcineurin activity.
AB  - Inherited prion diseases are linked to insertional and point mutations in the
      prion protein (PrP) gene, which favor conversion of PrP into a conformationally
      altered, pathogenic isoform. The cellular mechanism by which this process causes
      neurological dysfunction is unknown. Transgenic (Tg) (PG14) mice express a mouse
      PrP homolog of a nine-octapeptide insertion associated with an inherited prion
      disorder. These mice develop a progressive neurological syndrome characterized by
      ataxia and cerebellar atrophy due to synaptic degeneration in the molecular layer
      and massive apoptosis of granule neurons. To investigate the molecular events
      that may contribute to neurological dysfunction, we carried out a differential
      proteomic analysis of cerebella from Tg(PG14) mice at the preclinical, onset, and
      symptomatic phases of their neurological illness. 2-D maps of cerebellar proteins
      from Tg(PG14) mice were compared to those obtained from age-matched Tg(WT) mice
      that express wild-type PrP and remain healthy. Proteins whose levels were
      significantly modified in at least one stage of the Tg(PG14) disease were
      identified by PMF. Analysis detected a preclinical decrease of the
      calcium/calmodulin-dependent phosphatase calcineurin (CaN) in granule neurons,
      suggesting that dysregulation of CaN activity induced by mutant PrP may be
      responsible for the cerebellar dysfunction in Tg(PG14) mice.

PMID- 16572474
TI  - Regenerated silk fibroin nanofibers: water vapor-induced structural changes and
      their effects on the behavior of normal human cells.
AB  - Nanofibrous non-woven matrices were prepared by electrospinning a regenerated
      silk fibroin (SF) solution, and the structural changes of SF nanofibers treated
      with water vapor were investigated using time-resolved IR and (13)C CP/MAS NMR
      spectroscopy. Conformational transitions of SF from random coil to beta-sheet
      structures were induced by water vapor treatment and were strongly dependent on
      the treatment time and temperature. Water vapor treatment provided a useful means
      of stabilizing the SF nanofiber matrices, resulting in the formation of matrices
      with a decreased solubility in water and increased mechanical strength. The
      adhesion and spreading of both normal human keratinocytes and fibroblasts onto
      the SF nanofiber matrices were also investigated, and the water vapor-treated SF
      nanofiber matrices showed good cellular compatibility, in comparison with
      traditional methanol-treated ones. This approach to controlling the
      conformational changes of SF nanofibers by water vapor treatment may be useful in
      the design and tailoring of novel materials for biomedical applications,
      including wound dressings and scaffolds for tissue engineering.

PMID- 16572475
TI  - Composite magnetic particles as carriers for laccase from Trametes versicolor.
AB  - In this paper we report a study of laccase immobilisation on different kinds of
      carrier particles. The immobilisation of enzyme on the particle surface with
      respect to the immobilisation efficiency and the properties of the immobilised
      enzymes is discussed. The immobilisation of laccase on polystyrene particles
      bearing reactive beta-diketone groups is characterised by high efficiency, but
      grafting of the enzyme increases the stability of the colloidal system, which
      makes the separation/purification procedure difficult. Additionally, the extreme
      colloidal stability of the immobilisates hinders the application of such
      particles with immobilised enzymes in some applications where the recycling of
      the enzyme should be performed. It has been found that hybrid PS-AAEM particles
      equipped with maghemite show similar immobilisation efficiency to that of their
      analogues without maghemite and can additionally be manipulated in magnetic
      fields. The activity of the immobilised laccase is much higher in the pH region 5
      7 and the temperature range 50-70 degrees C as compared with that of the free
      enzyme. Immobilised enzymes also exhibit much better storage stability.

PMID- 16572476
TI  - Bioengineering Functional Copolymers. IX. Poly[(maleic anhydride-co-hexene-1)-g
      poly(ethylene oxide)].
AB  - Amphiphilic bioengineering copolymers having a combination of
      hydrophilic/hydrophobic linkages and polyelectrolyte behavior, along with an
      ability to interact with biomacromolecules, in particular with the invertase
      enzyme, have been synthesized by (a) complex-radical copolymerization of maleic
      anhydride (MA, the acceptor) and hexene-1 (H-1, the donor) monomers with benzoyl
      peroxide as the initiator in 1,4-dioxane at 65 degrees C under high-conversion
      conditions and (b) subsequent grafting (polyesterification) of synthesized
      poly(MA-alt-H-1) with alpha-methoxy-omega-hydroxy-poly(ethylene oxide) (PEO).
      Copolymerizations were also carried out in the steady state, in order to
      essentially reduce the effect of copolymer composition drift. The values of the
      monomer reactivity ratios (r(1) and r(2)) determined by using the known terminal
      models of Fineman-Ross (FR) and Kelen-Tudos (KT), as well as by nonlinear
      regression (NLR) analysis, are: r(1) = 0.16 and r(2) = 0.30 (FR), r(1) = 0.14 and
      r(2) = 0.27 (KT), and r(1) = 0.15 and r(2) = 0.29 (NLR), respectively. All the
      copolymers and graft copolymers were characterized by FTIR spectroscopy,
      (1)H{(13)C} NMR spectroscopy, viscometric measurements, and chemical (acid
      number), thermal (DSC and TGA), and X-ray diffraction analyses. Unlike poly(MA
      alt-H-1)s, PEO macrobranched graft copolymers exhibit expressed polyelectrolyte
      and swelling behavior in diluted and concentrated dioxane solutions,
      respectively. The copolymer and its PEO hyperbranched derivatives can be used as
      carriers for enzyme immobilization.

PMID- 16572477
TI  - Synthesis and antioxidant activity of new tetrahydro-naphthalene-indole
      derivatives as retinoid and melatonin analogs.
AB  - A number of retinoid-related compounds represent classes of antioxidative and
      proapoptotic agents with promising potential in the treatment of neoplastic
      diseases. Indeed, the synthetic retinoid amide fenretinide [N-(4
      hydroxyphenyl)retinamide] induces apoptosis of cancer cells and acts as a
      chemotherapeutic drug in cancer therapy. In the present work, and as a
      continuation of our studies on retinoid-type compounds, the synthesis of
      melatonin retinamide derivatives was studied as a novel series of melatonin
      retinoids, using the condensation reaction sequence involving
      tetrahydrotetramethylnaphthalene carboxylic acid and appropriate melatonin-type
      moieties. Despite of the weak DPPH inhibition activity pattern of the synthesized
      compounds, some of them showed a strong inhibition on lipid peroxidation (IVa-b,
      Va, and VIIa-c, 88, 96, 90, 94, 93, and 86%, respectively at 10(-4) M
      concentration) when melatonin (85% at 10(-4) M concentration) was used as a
      reference compound.

PMID- 16572478
TI  - Synthesis of new 3-(substituted phenacyl)-5-[3'-(4H-4-oxo-1-benzopyran-2-yl)
      benzylidene]-2,4-thiazolidinediones and their antimicrobial activity.
AB  - Synthesis of 3-(3-nitrophenacyl)thiazolidine-2,4-dione 2g and 3-(substituted
      phenacyl)-5-[3'-(4H-4-oxo-1-benzopyran-2-yl)-benzylidene]-2,4-thiazolidinediones
      4a-g are reported in this paper. These compounds 4a-g were prepared from 3'
      flavone carboxaldehyde and 3-substituted phenacyl-2,4-thiazolidinediones using
      Knoevenagel reaction. The structures of all compounds were confirmed by IR, 1H
      NMR, mass spectral data, and elemental analyses. The molecules 4a-g were
      evaluated for in-vitro antimicrobial activity against Staphylococcus aureus,
      Candida albicans, Candida krusei, Candida glabrata, and Candida parapsilosis.
      Compounds 4c and 4f showed better inhibitory activity when compared to
      fluconazole against Candida krusei and Candida glabrata.

PMID- 16572479
TI  - Molecular structure and QSAR study on antispasmodic activity of some xanthoxyline
      derivatives.
AB  - Semi-empirical molecular orbital calculations at AM1 level were done with the aim
      to investigate the structure-activity relationships of antispasmodic activities
      of ten 2-(X-benzyloxy)-4,6-dimethoxyacetophenones with X = H, 4'-F, 4'-NO2, 4'
      CH3, 4'-Cl, 3',4'-(CH3)2, 4'-OCH3, 4'-Br, 4'-OCH2C6H5, and 4'-C(CH3)3, against
      acetylcholine-induced contraction of the guinea pig ileum. The most significant
      quantum chemical descriptors for this series of compounds were the net atomic
      charges, nucleophilic and electrophilic frontier electron density, HOMO and LUMO
      orbitals, and reactivity indices. While no significant correlations were found
      employing molecular parameters such as heat of formation, dipole moment,
      molecular polarizability, and so on, good correlations were obtained using the
      reactivity indices of HOMO and LUMO orbitals at specific atoms of the molecules.
      These results indicate that the spatial distribution of HOMO and LUMO orbitals
      over these specific atoms play an important role for an increase of biological
      activity.

PMID- 16572480
TI  - Synthesis of substituted 3-anilino-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepine-2
      ones and their evaluation as cholecystokinin-ligands.
AB  - 3-Amino-1,4-benzodiazepines as well as chemically related diverse amines were
      prepared from oxazepam and subsequently screened on the cholecystokinin receptor
      in a radiolabel binding assay. Oxazepam 2 was activated via its 3-chloro-1,4
      benzodiazepine intermediate 3 and was reacted with a large series of aliphatic
      and aromatic amines. The substituted 3-anilino-1,4-benzodiazepine structure was
      identified as lead structure in a diverse series of 3-amino-1,4-benzodiazepines 4
      38 and the full SAR (structure-activity relationship) optimisation provided 3
      anilinobenzodiazepines 16-38 with CCK1 receptor selectivity to CCK2. The
      compounds 18, 24, 28 and 33 have shown affinities at the CCK1 receptor of 11, 10,
      11 and 9 nM, respectively. These equipotent CCK1 ligands were fully evaluated in
      behaviour pharmacological essays. An antidepressant effect was identified in the
      tail suspension- and the Porsolt swimming-test. The ED50 values for 24 and 28
      were determined in these assays as 0.46 and 0.49 mg/kg. The mixed antagonist 37
      showed in addition to the antidepressant effects anxiolytic properties.

PMID- 16572481
TI  - Synthesis and biological evaluation of heteroaryldiamides and heteroaryldiamines
      as cytotoxic agents, apoptosis inducers and caspase-3 activators.
AB  - The work described here involved the synthesis and biological evaluation of new
      heteroaryldiamides and heteroaryldiamines. A new general model in which the
      structures can be adjusted has been applied in this study. Three different
      structural units can be distinguished: a central nucleus and two symmetric
      terminal units. The central element is either an aliphatic chain of varying
      length and flexibility, piperazine, or a polyamine nucleus. However, the terminal
      units are pyridine, quinoline, indole, benzene or pyrido[2,3-d]pyrimidine with
      different substituents. The antitumoural activities of the compounds were
      evaluated in vitro by examining their cytotoxic effects against human breast,
      colon, and bladder cancer cell lines. Compounds that showed cytotoxic activity
      were subjected to both apoptosis and caspase-3 assays. With regard to
      selectivity, the cytotoxicity was also determined in cell cultures of two
      nontumoural lines. The most promising compounds are 4c, 5c and 7, which are amino
      pyridinium, quinolyl-N-oxide, and pyridyl derivatives, respectively, and these
      reveal a significant in vitro cytotoxicity in at least two of the three cell
      lines tested. These compounds induced apoptosis and also produced a rapid dose
      dependent increase in the caspase-3 level in HT-29 cells. Other encouraging
      profiles were found, such as those presented by 1k and 8d, which are cytotoxic
      and apoptotic but do not provoke an increase in the level of caspase-3, or those
      presented by 2f, 3c and 4a, which are slightly cytotoxic but do not show any
      other significant activity. The different types of behaviour of each compound are
      not necessarily parallel in the three cell lines tested.

PMID- 16572482
TI  - Synthesis and antifungal activity of 2-aryl-1,2,4-triazolo[1,5-a]pyridine
      derivatives.
AB  - A series of novel antifungal triazole derivatives 2-aryl-1,2,4-triazolo[1,5
      a]pyridine 9a-m were synthesized and tested in vitro for their growth inhibitory
      activities against C. albicans and T. rubrum. The MIC values indicate that the
      activities of three compounds were superior or comparable to fluconazole against
      both tested fungi, worthy of further investigation of its antifungal activities.

PMID- 16572483
TI  - Muscarinic allosteric modulators: atypical structure-activity-relationships in
      bispyridinium-type compounds.
AB  - Allosteric modulators of receptor binding are known for a variety of membrane
      receptors. In case of muscarinic receptors, a considerable number of structurally
      divergent modulators have been described. For the M2 receptor subtype which has a
      high sensitivity to allosteric modulation most of the allosteric agents bind to
      the common allosteric binding site of the receptor protein. In this study, a
      series of DUO compounds characterized by a bispyridinium middle chain and lateral
      benzyloximeether moieties of a systematically varied substitution pattern has
      been evaluated with regard to their allosteric potency to affect M2 receptors,
      whose orthosteric site was blocked by [3H]N-methylscopolamine. The variations in
      potency were found to be surprisingly small and the structure-activity
      relationships of the DUO compounds diverged from those of correspondingly
      substituted hexamethonio-type allosteric modulators. One has to conclude that DUO
      compounds bind in an "atypical" manner which is in agreement with recently
      reported side-directed mutagenesis and molecular modeling studies.

PMID- 16572484
TI  - Developing policies for 'psychopaths': can governments learn from experience?

PMID- 16572485
TI  - Women with antisocial behaviour: long-term health disability and help-seeking for
      emotional problems.
AB  - BACKGROUND: Previous studies have reported that women who display antisocial
      behaviour (ASB) as adults or adolescents are at increased risk of poor mental and
      physical health, but have not tested effects of sociodemographics, or used only
      incarcerated samples. AIMS: The authors sought first to test associations between
      ASB and emotional or physical health problems in non-incarcerated women, and
      second whether any such association could be explained by sociodemographic
      factors. METHOD: The sample was 1218 mothers, aged 22-59, of boys randomly
      selected from grades 1, 4 and 7 (aged about 7, 10 and 13 respectively) in US
      urban public schools in 1987 and 1988. The 30% of boys designated most antisocial
      on initial examination and a 30% random sample of the remainder entered the
      longitudinal study. Demographics for the mothers, data on their lifetime ASB,
      help-seeking for emotional and/or physical health problems were collected at
      interview with them. A history of adolescent conduct problems and/or lifetime
      police contacts led to classification as antisocial for this study. RESULTS: A
      total of 214 (17.6 %) of the mothers met our criteria for ASB. Compared with the
      women without such history, the women with ASB were younger, less well educated,
      of lower socioeconomic status, had a higher rate of unemployment and more of them
      were single mothers. They more often sought help for emotional problems and
      reported higher rates of long-term physical health problems, even when the
      effects of sociodemographic factors were taken into account. CONCLUSIONS:
      Although the findings rule out many sociodemographic factors as simple
      explanations for the association between ASB and poor emotional and physical
      health, more work is needed on the nature and extent of such disorder, and of
      temporal relationships between the key events: poor health and ASB.

PMID- 16572486
TI  - Increased deep sleep in a medication-free, detoxified female offender with
      schizophrenia, alcoholism and a history of attempted homicide: effect of
      concomitant administration of quetiapine and citalopram.
AB  - BACKGROUND: An increased amount of deep sleep has been shown to be associated
      with antisocial personality disorder. This phenomenon has also been observed in a
      habitually violent female offender with schizophrenia and alcohol dependence.
      AIM: To evaluate sleep patterns in this patient and compare them with those of
      healthy, pro-social women of similar age, and in the same patient over time after
      treatment. METHOD: Multiple measures of sleep were taken over two consecutive
      nights with the presenting patient and with three age-matched healthy women. One
      year after the patient was established on atypical antipsychotic (quetiapine),
      and antidepressant (SSRI) medication (citalopram) her sleep evaluation was
      repeated. In each case only the second night's recordings were used in analyses.
      RESULTS: The patient differed significantly from the three healthy women on most
      sleep measures. After a year on the medication, the patient's sleep had improved
      and the non-REM sleep measures had come into the normal range. She had also shown
      a sustained clinical and behavioural improvement. DISCUSSION AND IMPLICATIONS:
      The literature suggests that both drugs had a part to play in the improvements in
      sleep, symptomatology and behaviour. The possibility that improvement in deep
      sleep is secondary to citalopram and that it is this that was specifically
      associated with violence reduction seems worthy of further study.

PMID- 16572488
TI  - A secure attachment model of care: meeting the needs of women with mental health
      problems and antisocial behaviour.

PMID- 16572489
TI  - A comparison of offenders with intellectual disability across three levels of
      security.
AB  - BACKGROUND: A number of authors have described, with disparate results, the
      prevalence of people with intellectual disability and their characteristics, in a
      range of offender cohorts defined by service use. These have included high
      security, a range of criminal justice services and community services. There is a
      need for research comparing cohorts of offenders with intellectual disabilities
      across different settings. AIM AND HYPOTHESIS: To conduct such a comparison and
      test the hypothesis that severity of characteristics measured will be highest in
      highest levels of residential security. METHOD: A clinical-record-based
      comparison a offenders with intellectual disability in high security (n = 73),
      medium/low security (n = 70), and a community service (n = 69). RESULTS: Groups
      were similar in age and tested IQ levels. Early psychiatric service contact had
      been more likely in the lower security groups. In line with the hypothesis, more
      complex presentations, in particular comorbid personality disorder, was more
      likely in the highest security group. Both fatal and non-fatal interpersonal
      violence convictions were significantly related to group, with more in the high
      security group sustaining a conviction both at the index offence and prior to
      that. Over 50% of all groups had at least one conviction for a sexual offence. A
      regression model accounting for 78% of the variance was made up largely of
      disposal variables (Mental Health Act status and probation) and indications of
      antisocial traits (criminal damage, lifetime conviction for murder and ICD-10
      personality disorder classification). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      The authors show that context of sampling affects most relationships between
      intellectual disability (ID) and offending when the methods for measuring ID are
      held constant. The results also present several questions on the relationship
      between risk, services available in an area and referral to higher security.

PMID- 16572490
TI  - Social-cognitive determinants of help-seeking for mental health problems among
      prison inmates.
AB  - BACKGROUND: Prisoners experience high rates of mental health problems and
      suicidal behaviours. Failure to seek help may exacerbate these problems and limit
      opportunities to participate in offending-related programmes. AIMS: To assess
      whether prisoners'; intentions to seek help for a personal-emotional problem,
      including suicidal feelings, can be predicted using variables from the Theory of
      Planned Behaviour (TPB). These TPB variables were supplemented by measures of
      emotional distress, prior contact with a psychologist and demographic variables.
      METHODS: Male inmates from six New Zealand prisons were asked to participate,
      with approximately 50% (n = 527) of those who initially expressed an interest in
      the study completing the self-report questionnaire. Most participants completed
      the questionnaire in small-group meetings in the prison units and returned them
      to the researchers immediately after completion.Results On average, participants
      reported higher levels of current emotional distress than comparison student
      samples. TPB variables predicted help-seeking intentions for suicidality and
      personal-emotional problems. Those with prior contact with prison psychologists
      had lower intentions to seek help for suicidal feelings than prisoners without
      such contact. Older prisoners, those with more years of education, and those who
      had previous contact with a psychologist outside prison tended to have higher
      intentions to seek psychological help. CONCLUSIONS: Social-cognitive factors
      predicted intentions to seek help among New Zealand prisoners but prison-specific
      issues, such as relative reluctance to seek help when suicidal and reluctance to
      seek help from prison psychologists, were also identified. Implications for
      practice Prisoners'; access to services could be improved, for example, through
      directly working on attitudinal barriers. Strategies to ensure access to
      specialized forensic mental health in-reach services could also be an alternative
      or additional route to ensure that this disadvantaged group seeks appropriate
      help.

PMID- 16572491
TI  - Identical twins discordant for type 1 diabetes show a different pattern of in
      vitro CD56+ cell activation.
AB  - BACKGROUND: Recent studies in animal models indicate a role for natural killer
      (NK) cells in the protection against type 1 diabetes. In humans, a reduction of
      NK cell numbers has been reported in identical twins discordant for type 1
      diabetes, irrespective of whether they have the disease. Here we have tested
      whether the activation and expansion of human NK cells with lipopolysaccharide
      (LPS) reveals differences between these twins. METHODS: Proportions of CD56(+) NK
      cells and T-cells and Va24Vb11(+) NK-T cells from diabetic and non-diabetic twins
      was assessed before and after activation using flow cytometry. NK receptor usage
      was monitored by PCR and flow cytometry. RESULTS: The profile of the expressed
      Killer Cell immunoglobulin-like receptor (KIR) repertoire (using mRNA) in freshly
      isolated NK cells was identical in pairs of identical twins, despite marked
      variation among individual twins as well as controls. Basal numbers of CD56(+)
      and CD94(+) (CD3(-) and CD3(+)) cells and Valpha24(+)Vbeta11(+) NK-T cells were
      similarly strongly correlated between identical twins (p < 0.006 for all
      correlations). Following LPS stimulation, the pattern of KIR mRNA expression
      remained unaltered in twins and the proportion of NK cells and
      Valpha24(+)Vbeta11(+) NK-T cells remained correlated between pairs of twins.
      However, there was a significant reduction in the proportion of CD56(+) cells and
      CD94(+) cells (whether defined as CD3(-) or CD3(+)) responding to LPS in the
      diabetic compared to the non-diabetic twin (p = 0.031 and 0.025, respectively).
      CONCLUSION: This reduction in NK cell expansion in response to LPS in patients
      with type 1 diabetes is consistent with a non-genetically determined alteration
      in the innate immune response either predisposing to or resulting from the
      disease.

PMID- 16572492
TI  - Fluorescent 5-alkynyl-2'-deoxyuridines: high emission efficiency of a conjugated
      perylene nucleoside in a DNA duplex.
AB  - Four fluorescent 5-alkynyl-2'-deoxyuridines were studied in DNA oligonucleotides
      and their duplexes. The fluorescence response to hybridization differs
      dramatically for nucleosides containing a perylene fluorochrome either conjugated
      or not conjugated to the nucleobase. The conjugated nucleoside, 5-(perylen-3
      ylethynyl)-2'-deoxyuridine, shows enhanced long-wavelength emission in the DNA
      duplex, in contrast to the blue fluorescence of perylene on a flexible linker (in
      5-[(perylen-3-yl)methoxyprop-1-ynyl]-2'-deoxyuridine), which is quenched upon
      duplex formation.

PMID- 16572493
TI  - Characteristics of diabetic retinopathy in SDT rats.
AB  - BACKGROUND: We previously reported a new diabetic strain of the Sprague-Dawley
      rat, named the Spontaneously Diabetic Torii (SDT) rat. The purpose of the present
      study was to report the histologic and ultrastructural characteristics of
      diabetic retinopathy (DR) in a new animal model, the SDT rat. METHODS: Fifty
      three eyes of 43 SDT rats of various ages (35-82 weeks) were examined, of which
      33 underwent histopathologic examination, 15 eyes fluorescein-dextran microscopy,
      and five eyes the trypsin digestion method. RESULTS: Of the 33 eyes examined
      histopathologically, DR was identified in 20 eyes (61%). Large retinal folds
      mimicking diabetic tractional retinal detachment were observed in 20 eyes (61%).
      Retinal hemorrhages were seen in four eyes (12%). A neovascular fibrous membrane
      around the iris developed in five eyes (15%), of which two eyes had a massive
      anterior chamber hemorrhage. Of the 15 eyes examined by fluorescein-dextran
      microscopy, an area of nonperfusion and/or extensive hyperfluorescence was
      observed in 12 eyes (80%). Of the five eyes examined using the trypsin digestion
      method, acellular capillaries and pericyte loss were observed in four eyes (80%).
      Of the 53 eyes, the previously mentioned retinal changes of DR were observed in
      36 eyes (68%). The rats with DR (49-82 weeks; mean, 60 weeks) were older than the
      rats without DR (35-55 weeks; mean, 40 weeks) (p < 0.001). CONCLUSION: Large
      retinal folds mimicking tractional retinal detachment with extensive leakage of
      fluorescein around the optic disk was the most prominent finding of DR in SDT
      rats.

PMID- 16572494
TI  - Diminished IFN-gamma response to diabetes-associated autoantigens in children at
      diagnosis and during follow up of type 1 diabetes.
AB  - BACKGROUND: Imbalance of T-helper (Th)1- and Th2-like cytokines has been
      associated with type 1 diabetes. We therefore studied the immune deviation in
      antigen-specific T cells from diagnosis onwards in type 1 diabetic children.
      METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 15
      children after 4 days, 3 months and 18 months of being diagnosed with type 1
      diabetes, from 15 healthy children matched by age and gender to the type 1
      diabetic children and from 14 children with and 35 children without HLA-risk
      genes. Secretion of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was
      detected by ELISPOT after stimulation with glutamic acid decarboxylase (GAD(65),
      protein and aa 247-279), recombinant tyrosinphosphatase (IA-2), insulin,
      ovalbumin and phytohaemagglutinin (PHA). RESULTS: Secretion of IFN-gamma in PBMC
      stimulated with GAD(65) (p < 0.05), the GAD(65)-peptide (p < 0.01), IA-2 (p <
      0.01), and insulin (p < 0.01) was lower in diabetic children at diagnosis than in
      healthy children. Stimulation of PBMC with GAD(65) and IA-2 decreased the
      secretion of IFN-gamma in children with HLA-risk genotype. Spontaneous and
      antigen-induced IFN-gamma secretion increased significantly after diagnosis of
      the disease, but did not exceed the levels observed in healthy children. Fasting
      C-peptide levels at diagnosis correlated with insulin-induced IFN-gamma (R =
      0.52; p = 0.05) and negatively with spontaneous IL-4 secretion (R = -0.62; p <
      0.05). CONCLUSION: A diminished IFN-gamma secretion and the association of
      fasting C-peptide levels with cytokine response in children with type 1 diabetes
      suggest that factors related to beta-cell function in type 1 diabetes may modify
      T-cell function. Thus, the T-cell responses detected at or after diagnosis may
      not reflect the pathogenic process leading to type 1 diabetes.

PMID- 16572496
TI  - Direct intramolecular arylation of aldehydes promoted by reaction with
      IPy2BF4/HBF4: synthesis of benzocyclic ketones.

PMID- 16572495
TI  - Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein
      M gene (apoM) confer the susceptibility to development of type 2 diabetes in Han
      Chinese.
AB  - OBJECTIVE: Dyslipidemia correlating to insulin resistance is one of the key
      features in type 2 diabetes (T2D). Recent studies have demonstrated that
      apolipoprotein M (apoM) is important for the formation of prebeta-high-density
      lipoprotein (HDL) and cholesterol (CHO) efflux in macrophages to HDL. In the
      present study, we investigated the potential association of apoM genetic
      variation with the development of T2D. METHODS: Single nucleotide polymorphisms
      (SNPs) C-1065A, T-855C and T-778C in the proximal promoter region of apoM gene
      were validated to represent in Han Chinese. Further genotyping experiments in 170
      T2D patients and 156 non-diabetic control subjects were performed with polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS:
      Single marker analysis for SNP T-778C indicated that T2D patients had increased
      frequency of C allele in comparison with non-diabetic controls (10.6% versus
      5.8%, P = 0.026, OR = 1.934). In non-diabetic controls, the carriers with CT and
      CC genotypes had higher plasma CHO (221.7 versus 204.2 mg/dL, P = 0.033) and
      fasting plasma glucose (FPG) (92.6 versus 89.7 mg/dL, P = 0.041) levels than the
      subjects with TT genotype. Further analysis with adjustment for age, BMI, SBP,
      DBP, CHO and TG demonstrated that this SNP was strongly associated with T2D (P =
      0.013, OR = 2.287). Haplotype analysis for those three SNPs, however, indicated
      that the common haplotypes were less informative than studying the role of the T
      778C variant independently of the haplotype context. CONCLUSION: The present
      study provided the first evidence that SNP T-778C in the proximal promoter region
      of apoM gene was associated with the levels of plasma CHO and FPG and also
      conferred the risk in the development of T2D among Han Chinese.

PMID- 16572497
TI  - TiO2-based light-driven XOR/INH logic gates.

PMID- 16572498
TI  - Light-regulated release of DNA and its delivery to nuclei by means of photolabile
      gold nanoparticles.

PMID- 16572499
TI  - Catalytic properties of hierarchical mesoporous zeolites templated with a mixture
      of small organic ammonium salts and mesoscale cationic polymers.

PMID- 16572501
TI  - Catalytic carbon oxidation over ruthenium-based catalysts.

PMID- 16572500
TI  - Spatially encoded single-bead Biginelli synthesis in a microstructured silicon
      array.

PMID- 16572502
TI  - A bimetallic, coordinated-ketene complex formed from a bimetallic lithium-carbon
      spirocycle by lithium-mediated insertion of CO into a rhodium-carbon bond.

PMID- 16572503
TI  - Intracellular inducible alkylation system that exhibits antisense effects with
      greater potency and selectivity than the natural oligonucleotide.

PMID- 16572504
TI  - [Ildefonso Fernandez Aguado, president of the Spanish Society of Epidemiology.
      Spanish epidemiology stands out at the European and the international level.
      Interview by Marcelo Hansen].

PMID- 16572505
TI  - 2005 ASHG Presidential Address. If only we spoke the same language--we would have
      so much to discuss.

PMID- 16572506
TI  - Cover illustration. More than black and white.

PMID- 16572508
TI  - 2005 ASHG Award for Excellence in Human Genetics Education. Introductory speech
      of Joseph D. McInerney.

PMID- 16572509
TI  - 2005 ASHG Award for Excellence in Human Genetics Education. Education for health
      professionals and the public.

PMID- 16572511
TI  - Identification of frequent chromosome copy-number polymorphisms by use of high
      resolution single-nucleotide-polymorphism arrays.

PMID- 16572514
TI  - A second recombination hotspot associated with SHOX deletions.

PMID- 16572515
TI  - A penetrating look at how psychiatrists approach and avoid genetic issues.

PMID- 16572516
TI  - Cancer drug approved for RA.

PMID- 16572517
TI  - The broad-reaching power of statins. These "wonder" drugs offer an astounding
      range of benefits to treat--and prevent--heart disease.

PMID- 16572518
TI  - Cardiac surgery drug may cause more harm than good.

PMID- 16572519
TI  - Could you be at risk for metabolic syndrome? Experts believe Syndrome X
      contributes to diabetes, heart disease, vascular disease and stroke.

PMID- 16572520
TI  - Retin-A may help diabetic foot ulcers heal.

PMID- 16572521
TI  - Initial combo therapy best way to treat RA. Study shows MTX plus prednisone or
      the biologic infliximab may stop RA in its tracks.

PMID- 16572522
TI  - [1/7 Nurse midwives].

PMID- 16572523
TI  - [3/5 Child protection measures].

PMID- 16572524
TI  - [Three questions for...Jean-Francois Popielski. Interview by Pierre Chevry].

PMID- 16572525
TI  - Food labeling: health claims; dietary noncariogenic carbohydrate sweeteners and
      dental caries. Final rule.
AB  - The Food and Drug Administration (FDA) is announcing its decision to authorize
      the use of a health claim regarding the association between sucralose and the
      nonpromotion of dental caries. Based on its review of evidence described in the
      proposed rule and comments submitted on the proposed rule, the agency has
      concluded that sucralose does not promote dental caries. Therefore, the agency
      has decided to amend the regulation that authorizes a health claim regarding
      noncariogenic carbohydrate sweeteners to include sucralose.

PMID- 16572526
TI  - [Recurrent miscarriage and thrombophilia].

PMID- 16572527
TI  - DEFB-1 genetic polymorphism screening in HIV-1 positive pregnant women and their
      children.
AB  - OBJECTIVE: In our study we evaluated the frequency of three SNPs (-52 G/A, -44
      C/G; -20 G/A) in the 5' UTR of DEFB-1 gene, in a cohort of 130 HIV-1 infected
      mothers and their children, collected by the Italian group SIGO in Obstetrics and
      Gynecology. METHODS: The three SNPs (-52 G/A, -44 C/G; -20 G/A) in the 5' UTR of
      DEFB-1 gene were genotyped by direct sequencing of PCR products. RESULTS: The C
      allele at position -44 was shown to be significantly different in both HIV-1
      positive mothers and their children when compared to the healthy controls. The
      odds ratio for -44 C allele in children born to HIV-1 infected mothers is 7.09
      (confidence interval 3.38-15.3) while the odds ratio for this allele in HIV-1
      infected mothers is 6.42 (confidence interval 3.14-13.4). CONCLUSIONS: Our
      results evidence a high frequency of the -44 CC allele in HIV-1 infected mothers
      and their children with augmented potential risk of maternal fetal transmission.
      This potential vertical transmission risk has been successfully prevented by
      antiretroviral drug treatment and cesarian section of the HIV-1 positive mothers.

PMID- 16572529
TI  - Celebrating the life and work of Professor Joseph Goodman.

PMID- 16572530
TI  - Culture and continuing bonds: a prospective comparison of bereavement in the
      United States and the People's Republic of China.
AB  - There has been an increased interest and debate regarding the adaptiveness of
      continuing bonds with the deceased. The authors used data from a cross-cultural
      study of 61 participants from the United States (US) and 58 participants from the
      People's Republic of China (PRC) who completed measures of continuing bonds and
      adjustment at 4 and 18 months of bereavement. Higher levels of continuing bonds
      in the PRC at 4 months were related to better adjustment at 18 months. In
      contrast, results in the US showed that higher levels of continuing bonds were
      related to poorer adjustment at 18 months. The data suggest that culture should
      be addressed in the development of effective grief therapies, especially when
      considering continuing bonds with the deceased.

PMID- 16572531
TI  - Grief, glory, and political capital in the Capitol: presidents eulogizing
      presidents.
AB  - Kunkel and Dennis (2003) established a framework for the examination of
      contemporary eulogia drawn from the comforting and social support paradigms found
      in psychology and communication literatures. Dennis and Kunkel (2004) applied the
      framework to eulogies for fallen national heroes (e.g., victims of terrorism and
      space shuttle astronauts) delivered by American presidents, and both illustrated
      its utility and noted several minor variations (e.g., presidents did not
      establish credibility early in speeches or portray emotion as individual
      experiences). The current study illuminates the nature of eulogies for past
      presidents by sitting presidents, and examines the eulogies of Presidents John
      Kennedy, Dwight Eisenhower, Richard Nixon, and Ronald Reagan by Presidents Lyndon
      Johnson, Nixon, William Clinton, and George W. Bush, respectively. As highlighted
      by Kunkel and Dennis' framework, these eulogists accomplish many of the
      recognized comforting and consolation responsibilities. The presidents sometimes
      further their own causes and agendas when considered in hindsight, in ironic and
      prophetic fashion; thus, also meeting Jamieson and Campbell's (1982) definition
      of the rhetorical hybrid. Finally, the destiny and glory of the eulogized are
      often noted by eulogists, continuing the legacy that started with the death of
      George Washington, America' first president (Berens, 1977).

PMID- 16572532
TI  - Body modification and suicidal behavior.
AB  - In a large sample of individuals who belong to a website for body modification,
      having body modifications (e.g., piercings, tattoos, scarification and surgical
      procedures) was associated with a higher incidence of prior suicidality (i.e.,
      suicidal ideation and attempted suicide). However, controls for self-reported
      depression weakened the strength of these associations.

PMID- 16572533
TI  - Religiosity and death distress in Arabic college students.
AB  - The purpose of the present study was to explore the relationship between
      religiosity and death distress (death anxiety, death depression, and death
      obsession) among a sample (N = 570) of Egyptian women nursing undergraduates,
      mainly Muslims. Their ages ranged from 17 to 25. The correlations between
      religiosity and both death anxiety and death depression were significant and
      negative, whereas the correlation between religiosity and death obsession was
      not. Significant, positive and high correlations were found between the different
      scales of death distress. Factor analysis of all the correlations yielded a
      single, salient, and bipolar factor labeled 'death distress versus religiosity.'
      It was argued that different situational variables may have had influenced the
      conceptual relationship between religiosity and death distress, including the
      young ages of the present sample.

PMID- 16572534
TI  - Prospective nurses' appraisals of screening for child neglect in primary care
      settings.
AB  - Screening for child neglect in primary care settings is a well-recognized, though
      largely untapped, resource in the campaign to prevent this pervasive childhood
      morbidity. Using a contemporary cognitive appraisal model as a conceptual guide,
      this study evaluated 71 upper-level undergraduate nursing students' thoughts
      about their future professional responsibility to screen children and families
      for child neglect. Seventy-one upper-level undergraduate nursing students
      voluntarily and independently completed a brief, 10-minute survey during a
      regularly scheduled class meeting. Data showed that participants perceived
      screening for neglect as important to and consistent with their future
      professional objectives. In addition, participants reported confidence in their
      ability to screen for neglect and to better the lives of children and families
      through universal screening procedures. In contrast, the majority of participants
      doubted their ability to emotionally tolerate the psychologic burden of routinely
      assessing caregivers' ability to nurture and protect their offspring. Although
      the majority of participants reported some degree of anxiety and a substantial
      minority reported some degree of hopelessness about screening for neglect, most
      were hopeful that this challenge would yield personal and professional benefits.
      Overall, data suggested that participants were highly motivated to invest
      cognitive and emotional resources in learning more about screening for child
      neglect in primary care settings.

PMID- 16572535
TI  - Attention-deficit/hyperactivity disorder: diagnostic assessment methods used by
      advanced practice registered nurses.
AB  - BACKGROUND: Children presenting with symptoms of attention-deficit/hyperactivity
      disorder (ADHD) have become highly prevalent in primary care practice; however,
      advanced practice registered nurses (APRNs) diagnostic methods used to identify
      and diagnose this disorder are greatly understudied. AIM: This study aimed to
      identify APRNs recognition and diagnostic practices of children who were
      suspected of having an ADHD diagnosis. It also addressed APRNs comfort levels
      with treating and diagnosing ADHD, along with certain diagnostic methods and
      their perceived accuracy of these methods. METHODS: This nonexperimental
      exploratory research study used a self-administered questionnaire to gather
      information about diagnostic methods used by APRNs who diagnose children with
      ADHD, treat the disorder, or did both. RESULTS AND DISCUSSION: The questionnaires
      identified that the APRNs were following the American Academy of Pediatrics
      diagnostic guidelines for diagnosing ADHD in children more closely than other
      health care providers (pediatricians and family physicians). The results of this
      study also indicated that most APRNs were very comfortable to comfortable making
      an ADHD diagnosis (52.5%), and 64.4% reported the same level of comfort with
      treating ADHD. These findings indicate that the majority of APRNs surveyed who
      works with children are comfortable with diagnosing and treating ADHD.

PMID- 16572536
TI  - Wheezing and asthma in early childhood: an update.
AB  - Although asthma is the most common chronic disease in children, recent studies
      show that labeling this condition "asthma," especially in association with
      chronic wheezing, remains a matter of dispute. Nonetheless, data confirm that
      wheezing and asthma place great burdens on the caregivers of affected children. A
      principal source of information on diagnosis and treatment is the practical guide
      published by the National Asthma Education Prevention Program. The implications
      for nurses in the management of young children whose wheezing is chronic or who
      have been diagnosed as having asthma include a need for knowing the program
      guide's recommendations, assessing the child's family history, teaching primary
      caregivers an action plan, providing consistent asthma education, encouraging
      parents to evaluate the child's environment, and identifying related resources.

PMID- 16572537
TI  - Preparing children and families for surgery: Mount Sinai's multidisciplinary
      perspective.
AB  - Upon learning that they must undergo surgery, children experience a range of
      emotions including fear, anger, guilt, and sadness. It has been demonstrated that
      children who are prepared for surgery and who have support throughout their
      hospitalization recover more quickly and have fewer emotional problems, such as
      separation anxiety and sleep disturbances, than those who are not prepared. Pre
      surgical preparation programs allow children and their families the opportunity
      to preview the hospital experience in a supportive environment to reduce anxiety,
      increase knowledge, and enhance coping. Meet Me at Mount Sinai (MMAMS) is an
      innovative preoperative preparation program for children and their families that
      seeks to provide comprehensive emotional and cognitive preparation for surgery.
      MMAMS is led by a multi-disciplinary team of health care providers including a
      pediatric surgery nurse practitioner, a registered nurse, a social worker, and a
      child life specialist. The program utilizes a culturally-sensitive, multimodality
      preparation model to prepare children and families for the surgical experience.

PMID- 16572539
TI  - Parenting a child with chronic illness: a metasynthesis.
AB  - Increasing numbers of children are diagnosed with chronic illnesses each year.
      Some parents are finding themselves providing all the care to these children. The
      experience of parents caring for a child with a chronic illness is examined in
      this metasynthesis.

PMID- 16572538
TI  - Cross-cultural beliefs, ceremonies, and rituals surrounding death of a loved one.
AB  - The purpose of this qualitative study was to describe practices surrounding death
      of a loved one by European, Asian, Caribbean, Central American, and South
      American families living in the United States. A focus group with 14 masters
      nursing students from a wide variety of cultural and religious backgrounds was
      conducted to gain a better understanding of the beliefs, ceremonies, and rituals
      surrounding death. Many commonalties were found across cultures and religions. A
      pervasive theme was that beliefs about the soul of the deceased lead families to
      perform rituals and ceremonies that foster passage to God, the "light," or
      another life. The stronger their beliefs, the more dedicated the family is in
      completing the rituals and ceremonies in the way dictated by their religion or
      culture. Participants had difficulty separating the influence of culture and
      religion on these practices.

PMID- 16572540
TI  - Family health nursing and empowering relationships.
AB  - PURPOSE: To examine how empowerment, as an ideology and a practice of teaching
      and learning, was understood and applied by public health nurses (PHNs) in health
      education with child bearing and child rearing families. METHOD: Feminist
      poststructuralism was used to guide data collection and analysis. In-depth,
      individual interviews were conducted with three mothers and three PHNs and
      explored the different perspectives held by mothers and PHNs during a home visit.
      FINDINGS: Moments of conflict, contradiction, affirmation, and agreement
      highlighted various empowering relations. Individual choice and recognition of
      knowledge and power exemplified how both mothers and PHNs used their "agency" to
      position themselves into a particular relationship. The analysis includes five
      sections: (a) mother's perceptions of PHNs, (b) normalization as problematic: the
      good/bad dichotomy, (c) professional/expert: the balance of power, (d) working
      the relationship, and (e) reflections on empowerment. CONCLUSION: The information
      gathered from this studyprovides a rich understanding of the nurses' educational
      practices with new mothers.

PMID- 16572541
TI  - An ethics conflict and culture: should this kidney be used?
AB  - The practice of nursing in transplant medicine is often fraught with ethical
      complexity. It is especially so when children are involved as potential living
      donors. This is no less true when the donor "child" is of consenting age, and
      when the intended recipient is the parent. This case is presented by a clinical
      ethics consultant to whom a nurse turned with her discomfort over the situation
      faced as a renal transplant coordinator. The part played by ethnicity and
      traditional Korean culture is highlighted.

PMID- 16572542
TI  - The smallest victims of the "White Plague".

PMID- 16572543
TI  - Changes in the screening for tuberculosis in children.

PMID- 16572544
TI  - Avian influenza pandemic: not if, but when.

PMID- 16572545
TI  - 18-year-old college woman with fatigue.

PMID- 16572546
TI  - This is the best life yet--life at Camp Friendship.

PMID- 16572547
TI  - Supporting fathers' involvement in children's health care.
AB  - Although mothers are generally more likely than fathers to be involved with their
      child's health care needs, incorporating fathers is important as well. Some
      research suggests that factors interfering with paternal involvement include work
      conflicts and greater convenience for mothers accompanying the child to health
      care visits. One factor fathers have identified as a positive motivator is a
      health care provider's specific invitation or encouragement to attend the child's
      appointments. Fathers and mothers may cope differently with a child's illness or
      disability, and the type of support each parent needs may vary. Health care
      providers can increase their own awareness of paternal concerns and needs to best
      encourage paternal involvement.

PMID- 16572548
TI  - Nurses: taking precautionary action on a pediatric environmental exposure: DEHP.
AB  - Di(2-ethylhexyl) phthalate, or DEHP, is a chemical used to soften rigid polyvinyl
      chloride (PVC) plastic. Medical devices made of flexible PVC, such as intravenous
      (IV) bags and tubing, contain DEHP to make them pliable and soft. Animal studies
      show that exposure to DEHP can damage the liver, kidneys, lungs, and reproductive
      system, particularly the developing testes of prenatal and neonatal males.
      Because of this, the U.S. Food and Drug Administration (FDA) has issued a Public
      Health Notification on PVC devices containing DEHP, urging health care providers
      to use DEHP-free devices for certain vulnerable patients. Many hospitals and
      health systems have successfully transitioned away from use of DEHP, particularly
      in neonatal intensive care units (NICUs).

PMID- 16572549
TI  - Providing pediatric palliative care through a pediatric supportive care team.

PMID- 16572550
TI  - The effect of a nursing staff education program on compliance with central line
      care policy in the cardiac intensive care unit.

PMID- 16572552
TI  - The people who tell the story, shape the culture.

PMID- 16572553
TI  - Science and music; music and science; the science of music; the music of science
      (and the making of "body notes," a symphonic suite about human physiology).

PMID- 16572554
TI  - Report on a satellite symposium to the XXXV International Congress of
      Physiological Sciences.

PMID- 16572555
TI  - Reflections on satellite symposium of XXXV IUPS Mechanisms of Acupuncture
      Treatment in Disease.

PMID- 16572556
TI  - Breathless in San Diego.

PMID- 16572557
TI  - Research priorities in urothelial cell physiology: a report on the IUPS satellite
      meeting.

PMID- 16572558
TI  - Prevention of respiratory complications of spinal cord injury: a challenge to
      "model" spinal cord injury units.

PMID- 16572559
TI  - James J. Peters Memorial Lecture. Carrying the torch: a call to build on the
      progress of the past 25 years.

PMID- 16572560
TI  - Fournier gangrene in spinal cord injury: a case report.

PMID- 16572561
TI  - Racial disparities in health outcomes after spinal cord injury: mediating effects
      of education and income.
AB  - OBJECTIVE: The purpose of this study was to investigate heath disparities as a
      function of race and gender and the extent to which socioeconomic factors mediate
      disparities among participants with spinal cord injury. DESIGN: Survey
      methodology. Cross-sectional data. SETTING: A large Southeastern specialty
      hospital. PARTICIPANTS: There were 1342 participants in the current analysis, all
      of whom were identified from patient records. There were 3 inclusion criteria:
      (a) traumatic SCI, (b) at least 18 years of age at the time of study, and (c)
      injury duration of more than 1 year. MAIN OUTCOME MEASURES: Six outcomes were
      measured, including 3 general outcomes (self-ratings, days impacted by poor
      health, days impacted by poor mental health) and 3 that reflect utilization of
      services (hospitalizations, days hospitalized, and nonroutine physician visits in
      the past 2 years). RESULTS: RESULTS of multivariate analysis of variance (MANOVA)
      indicated significant main effects for both race and gender. Follow-up tests
      identified racial disparities on 3 of the 6 outcomes, whereas gender disparities
      were observed for a single outcome. Years of education and household income
      mediated interrelationships between race and health (but not gender) as racial
      disparities disappeared after consideration of these factors. CONCLUSIONS: These
      findings suggest the need to work more diligently to promote better health
      outcomes among African Americans and to further investigate how socioeconomic
      factors and access to health care related to diminished health outcomes among
      African Americans with spinal cord injury.

PMID- 16572562
TI  - Normal ranges of variability for urodynamic studies of neurogenic bladders in
      spinal cord injury.
AB  - BACKGROUND/OBJECTIVE: Urodynamic studies are conducted on a regular basis to
      evaluate changes in bladder function after spinal cord injury. Often, differences
      in urodynamic parameters exist from one study or one year to the next. The
      objective of this study was to provide reference ranges for "normal" variability
      in urodynamic parameters that can be considered as "no real change" from one
      study to the next. DESIGN: Retrospective chart review. METHODS: Fifty consecutive
      individuals with spinal cord injury had 2 trials (trial 1 and trial 2) of
      urodynamic studies done 5 minutes apart, and the following data were collected:
      maximum cystometric capacity, opening pressure, maximum detrusor pressure, volume
      voided, and postvoid residual. The corresponding data were compared, and the
      frequency distribution for the change between consecutive studies was plotted.
      Because there is no standard, variability ranges for 5th to 95th, 10th to 90th,
      and 25th to 75th percentiles were calculated to give health care providers more
      choices. RESULTS: Ranges of variability are as follows in the following format
      (urodynamic parameter; mean value; +, maximum increase; -, maximum decrease)--5th
      to 95th percentile: cystometric capacity (234.63 mL, +213.50 mL, -158.05 mL);
      opening pressure (54.56 cmH2O, +30 cmH2O, -18.00 cmH2O); maximum detrusor
      pressure (60.82 cmH2O, +17.35 cmH2O, -27.80 cmH2O); volume voided (122.20 mL,
      +177.25 mL, -176.00 mL); postvoid residual (176.06 mL, +197.25 mL, -118.00 mL);
      10th to 90th percentile: cystometric capacity (234.63 mL, +126.40 mL, -74.60 mL);
      opening pressure (54.56 cmH2O, +13.70 cmH2O, -12.00 cmH2O); maximum detrusor
      pressure (60.82 cmH2O, +10.00 cmH2O, -20.00 cmH2O); volume voided (122.20 mL,
      +105.60 mL, -82.00 mL); postvoid residual (176.06 mL, +131.00 mL, -86.00 mL);
      25th to 75th percentile: cystometric capacity (234.63 mL, +72.00 mL, -27.00 mL);
      opening pressure (54.56 cmH2O, +4.00 cmH2O, -9.50 cmH2O; maximum detrusor
      pressure (60.82 cmH2O, +4.00 cmH2O, -10.00 cmH2O); volume voided (122.20 mL,
      +50.00 mL, -30.00 mL); postvoid residual (176.06 mL, +50.00 mL, -30.00 mL).
      CONCLUSIONS: Urodynamic studies have variability. Knowing these ranges of
      variability can be helpful in determining whether differences between filling
      trial 1 and filling trial 2 in a single study or year-to-year changes in
      urodynamic studies are significant or simply the normal variability of the
      urodynamic study.

PMID- 16572563
TI  - Efficacy of surgical decompression in regard to motor recovery in the setting of
      conus medullaris injury.
AB  - BACKGROUND/OBJECTIVE: An assessment of neurological improvement after surgical
      intervention in the setting of traumatic conus medullaris injury (CMI). METHODS:
      A retrospective evaluation of a cohort of patients with a blunt traumatic CMI
      from T12 to L1. The neurologic and functional outcomes were recorded from the
      acute hospital admission to the most recent follow-up. Data collected included
      age, level of injury, neurologic examination according to the Frankel grading
      system and motor index score, and the mechanism and timing of CMI decompression.
      RESULTS: A total of 24 patients with a mean age of 27 years (men, 87%) were
      identified. The most common level of bony injury was L1, and the most frequent
      mechanism of injury was a motor vehicle crash. Before surgical intervention, 16
      of 24 patients (66.7%) had a complete neurological deficit below the level of
      injury. The median interval from injury to surgery was 6 days (range, 7 hours to
      390 days). Decompression, fusion, and adjunctive internal fixation were the most
      common surgical procedures. Median length of follow-up was 32 months after
      surgery. Improvement in spinal cord and bladder function was seen in 41.6% and
      63.6% of patients, respectively. Root recovery was seen in 83.3% of patients.
      CONCLUSIONS: In the setting of CMI, no correlation between the timing of surgical
      decompression and motor improvement was identified. Root recovery was more
      predictable than spinal cord and bladder recovery.

PMID- 16572564
TI  - Construct validity and dimensional structure of the ASIA motor scale.
AB  - BACKGROUND/OBJECTIVE: The use of the American Spinal Injury Association (ASIA)
      motor score as an outcome measure requires metrological study. This paper tests
      the hypothesis that a more accurate representation of motor function is obtained
      using separate upper and lower extremity scales rather than combining all 20 key
      muscle ratings into a single ASIA motor score. METHODS: We analyzed archived data
      from 6116 ASIA motor scale records extracted from the National Spinal Cord Injury
      Statistical Center Database. RESULTS: The hypothesis that separate scales more
      accurately represent motor function than a single motor scale was supported
      (chi2(difference) = 2596; df=1; P < 0.0001). Two scales account for 87% of the
      variance, whereas a single scale accounts for only 82%. Lower extremity function
      is well represented in both solutions; however, upper extremity function is
      accurately represented only with the use of 2 separate scales. CONCLUSIONS: The
      use of components of the ASIA standards for other than classification of spinal
      cord injury needs study. Several lines of study converge to provide strong
      support for the existence of 2 distinctive dimensions underlying the ASIA motor
      scale. The use of a single motor score in spinal cord injury research should be
      questioned and justified to the extent possible. The use of upper and lower
      extremity scales will lead to a reduction in measurement error when the motor
      score is used as an outcome measure. The confirmation of 2 separate dimensions
      underlying the ASIA motor score will enable more accurate representation of motor
      function in spinal cord injury research.

PMID- 16572565
TI  - Stability of transition to adulthood among individuals with pediatric-onset
      spinal cord injuries.
AB  - BACKGROUND/OBJECTIVE: Cross-sectional studies have provided information about the
      outcomes of adults with pediatric-onset spinal cord injuries (SCIs), but there
      has been no information about the stability of those outcomes over time. The
      purpose of this study was to assess the stability of independent living,
      employment, and life satisfaction and to determine factors associated with
      stable, successful outcomes. METHODS: Structured interviews of individuals who
      had sustained an SCI at age 18 years or younger and were 24 years or older at
      first interview. The primary standardized measures used include the Functional
      Independence Measure, Craig Handicap Assessment and Recording Technique (CHART),
      Short-Form 12 measure of perceived health, and the Satisfaction with Life Scale.
      RESULTS: One hundred sixty-six individuals had 3 consecutive annual interviews.
      Mean age at interview was 29 years (range, 24-36 years). Of this group, 64% lived
      independently at the first interview, and 90% of those continued to live
      independently; 64% were employed at first interview, of which 83% continued to be
      employed; and 48% reported life satisfaction at the first interview, and 84% of
      these continued to be satisfied. Factors most closely associated with stable
      independent living were CHART subscales of physical independence, mobility, and
      occupation. Factors associated with stable employment were sex, race, independent
      living, CHART mobility, and cognitive independence. Factors associated with
      stable life satisfaction were CHART occupation subscale and fewer pressure
      ulcers. CONCLUSIONS: Many individuals with pediatric-onset SCI achieve
      successful, stable adult outcomes. The factors associated with that success can
      help us improve rehabilitation for future patients.

PMID- 16572566
TI  - Involvement of peripheral adenosine A2 receptors in adenosine A1 receptor
      mediated recovery of respiratory motor function after upper cervical spinal cord
      hemisection.
AB  - BACKGROUND/OBJECTIVE: In an animal model of spinal cord injury, a latent
      respiratory motor pathway can be pharmacologically activated through central
      adenosine A1 receptor antagonism to restore respiratory function after cervical
      (C2) spinal cord hemisection that paralyzes the hemidiaphragm ipsilateral to
      injury. Although respiration is modulated by central and peripheral mechanisms,
      putative involvement of peripheral adenosine A2 receptors in functional recovery
      in our model is untested. The objective of this study was to assess the effects
      of peripherally located adenosine A2 receptors on recovery of respiratory
      function after cervical (C2) spinal cord hemisection. METHODS: Respiratory
      activity was electrophysiologically assessed (under standardized recording
      conditions) in C2-hemisected adult rats with the carotid bodies intact (H-CBI;
      n=12) or excised (H-CBE; n=12). Animals were administered the adenosine A2
      receptor agonist, CGS-21680, followed by the A1 receptor antagonist, 1,3-dipropyl
      8-cyclopentylxanthine (DPCPX), or administered DPCPX alone. Recovered respiratory
      activity, characterized as drug-induced activity in the previously quiescent left
      phrenic nerve of C2-hemisected animals in H-CBI and H-CBE rats, was compared.
      Recovered respiratory activity was calculated by dividing drug-induced activity
      in the left phrenic nerve by activity in the right phrenic nerve. RESULTS:
      Administration of CGS-21680 before DPCPX (n=6) in H-CBI rats induced a
      significantly greater recovery (58.5 +/- 3.6%) than when DPCPX (42.6 +/- 4.6%)
      was administered (n=6) alone. In H-CBE rats, prior administration of CGS-21680
      (n=6) did not enhance recovery over that induced by DPCPX (n=6) alone. Recovery
      in H-CBE rats amounted to 39.7 +/- 3.7% and 38.4 + 4.2%, respectively.
      CONCLUSIONS: Our results suggest that adenosine A2 receptors located in the
      carotid bodies can enhance the magnitude of adenosine A1 receptor-mediated
      recovery of respiratory function after C2 hemisection. We conclude that a novel
      approach of targeting peripheral and central adenosine receptors can be
      therapeutically beneficial in alleviating compromised respiratory function after
      cervical spinal cord injury.

PMID- 16572567
TI  - Adrenal insufficiency in acute spinal cord injury.
AB  - BACKGROUND/OBJECTIVE: A 21-year-old man with a C6 American Spinal Injury
      Association A spinal cord injury (SCI) developed symptomatic hypotension
      resistant to vasopressors and volume replacement 2 weeks after injury and was
      diagnosed with adrenal insufficiency by cosyntropin test. Adrenal insufficiency
      has been documented in chronic SCI; this case shows documented adrenal
      insufficiency in acute SCI. DESIGN: Case report. RESULTS: Secondary adrenal
      insufficiency complicated the medical and rehabilitative course of this patient
      with SCI. During 2 infectious episodes, this patient's dosage of hydrocortisone
      had to be doubled to control symptomatic hypotension, lethargy, diffuse weakness,
      and anorexia. CONCLUSIONS: The nonspecific symptomatology of adrenal
      insufficiency can be easily overlooked in patients with SCI. Low basal cortisol
      levels may be an important clue to this disorder. Low-dose adrenocorticotropic
      hormone stimulation may be more sensitive than high doses for detecting
      subclinical adrenal insufficiency. A high index of clinical suspicion is needed
      for the correct diagnosis of acute and chronic adrenal insufficiency.

PMID- 16572568
TI  - Rehabilitation Medicine Summit: building research capacity.
AB  - The general objective of the "Rehabilitation Medicine Summit: Building Research
      Capacity" was to advance and promote research in medical rehabilitation by making
      recommendations to expand research capacity. The five elements of research
      capacity that guided the discussions were: (1) researchers; (2) research culture,
      environment, and infrastructure; (3) funding; (4) partnerships; and (5) metrics.
      The 100 participants included representatives of professional organizations,
      consumer groups, academic departments, researchers, governmental funding
      agencies, and the private sector. The small group discussions and plenary
      sessions generated an array of problems, possible solutions, and recommended
      actions. A post-Summit, multi-organizational initiative is called to pursue the
      agendas outlined in this report.

PMID- 16572569
TI  - Do as I say, not as I do. The new epidemic of childhood obesity.

PMID- 16572570
TI  - Shoring up professionalism. Building on disagreements between residents and
      attending physicians.

PMID- 16572571
TI  - Ethical concerns in community practice research. Common concerns encountered by
      the Alberta family practice research network.

PMID- 16572572
TI  - Screening for alcohol abuse.

PMID- 16572573
TI  - Safety of gadolinium during pregnancy.
AB  - QUESTION: A pregnant patient who underwent magnetic resonance imaging (MRI)
      because of an acute abdomen, was told that MRI contrast agents (ie, gadolinium
      based contrast agents) are contraindicated during pregnancy. What is the risk to
      her baby? ANSWER: Current radiology practices and recommendations discourage the
      use of gadolinium-based contrast agents during pregnancy because their safety for
      the fetus has not yet been proven. In line, however, with the European Society of
      Radiology guidelines and based on the available evidence, gadolinium-based
      contrast agents appear to be safe in pregnancy. Gadolinium use should be
      considered when the diagnostic study is important for the health of the mother.

PMID- 16572574
TI  - Should we use steroids to treat children with Bell's palsy?
AB  - QUESTION: A healthy 6-year-old boy came to my office with severe Bell's palsy
      that had lasted for 24 hours following an upper respiratory tract infection he
      had had a little over a week ago. Should I treat him with steroids? ANSWER: While
      there is currently no definitive answer, the risk that Bell's palsy will become
      permanent seems exceptionally small in children (even smaller than in adults),
      and the best evidence demonstrates no benefit from steroids. Until a large
      randomized controlled trial can prove benefit, these patients should not be
      treated with steroids. The vast majority will recover fully without treatment.

PMID- 16572575
TI  - Sebaceous cysts. Ten tips for easier excision.

PMID- 16572576
TI  - Does low-dose ASA help prevent cardiovascular events in women?

PMID- 16572577
TI  - Preventing and managing pediatric obesity. Recommendations for family physicians.
AB  - OBJECTIVE: To review the evidence on prevention and management of childhood
      obesity and to offer suggestions for family physicians. QUALITY OF EVIDENCE:
      Articles were obtained from a PubMed search. Most studies on pediatric obesity
      provide level II evidence. There are some level I studies on management. MAIN
      MESSAGE: Pediatric obesity is underdiagnosed and undertreated. Prevention should
      be initiated as early as pregnancy. Prevention and treatment approaches should
      include patient and family interventions focusing on nutrition, physical
      activity, reduced television viewing, and behaviour modification. The
      effectiveness of such interventions by primary care physicians has not been
      totally demonstrated, but incorporating them into clinical practice routines is
      likely to be beneficial. CONCLUSION: Family physicians have a role in promoting
      preventive measures and identifying and treating obesity-related comorbidity.
      Pediatric obesity is not an individual child's problem, but a problem that
      involves the whole family and the community. Recommending a healthy diet and
      increased physical activity and counseling families on behaviour change is the
      best approach to preventing and managing childhood obesity.

PMID- 16572578
TI  - What is medicine? Recruiting high-school students into family medicine.
AB  - PROBLEM ADDRESSED: Family medicine is a vital part of health care in Canada. The
      decline in numbers of new family physicians being trained bodes ill for a
      sustainable and efficacious health care system. We need to recruit young people
      more effectively into careers in primary care. Early outreach to high-school
      students is one approach that holds promise. OBJECTIVE OF PROGRAM: To provide
      high-school students with exposure to and appreciation for careers in medicine,
      particularly family medicine. PROGRAM DESCRIPTION: Family medicine residents in
      the University of Alberta's Rural Alberta North Program initiated an outreach
      project that was implemented in rural and regional high schools in northern
      Alberta. The program consisted of visits to high schools by residents who gave
      interactive presentations introducing medicine as a career. The regional hospital
      subsequently hosted a career day involving medical and paramedical professionals,
      such as physicians, pharmacists, nurses, and physical and occupational
      therapists. CONCLUSION: Physicians' visits to high-school students could be an
      effective way to increase interest in careers in rural family medicine.

PMID- 16572579
TI  - Case report: profound anemia. Chronic disease detection and global health
      disparities.

PMID- 16572580
TI  - Pediatric care.

PMID- 16572581
TI  - Whose pen is in your pocket?

PMID- 16572582
TI  - Nurses: empowered to make changes.

PMID- 16572583
TI  - Organizing a union just makes sense!

PMID- 16572584
TI  - More than a cookie. Interview by Ann Kettering Sincox.

PMID- 16572585
TI  - Five steps to good communication.

PMID- 16572586
TI  - Vascular endothelial growth factor (VEGF) is suppressed in WT1-transfected LNCaP
      cells.
AB  - The Wilms' tumor suppressor gene product (WT1) regulates expression of growth
      control genes. Microarray analysis of gene expression profiles of hormone-treated
      LNCaP prostate cancer cell lines transfected with either wild-type WT1 or a zinc
      finger mutant form, DDS (R394W), revealed significantly altered patterns of
      expression. Validation studies using quantitative real-time PCR confirmed the
      differential expression of the tumor progression gene, vascular endothelial
      growth factor (VEGF). WT1-LNCaP cells had significantly reduced levels of VEGF
      mRNA when compared to vector control cells; in contrast, DDS-LNCaP cells showed
      elevated levels of VEGF transcripts. To address a functional role for WT1
      overexpression, we investigated whether induction of VEGF expression, by the
      synthetic androgen R1881, would be disrupted in wild-type or mutant WT1
      transfected LNCaP cells. Hormone treatment failed to elevate VEGF transcript
      levels above uninduced baseline levels in WT1-LNCaP cells, despite 48 h of
      treatment with 5 nM R1881. Consistent with our quantitative real-time PCR
      analysis, immunofluorescent staining of VEGF protein was reduced in WT1-LNCaP
      cells in both the presence and absence of R1881 treatment. Conversely, VEGF
      levels increased in vector control and DDS-LNCaP cells treated with 5 nM R1881.
      Not only do these studies point out the regulatory potential of WT1 for VEGF, but
      they also indicate an altered function for the mutant DDS isoform. Because VEGF
      is associated with neovascularization and promotion of metastasis in a variety of
      solid tumors including prostate cancer, a better understanding of the regulation
      of VEGF expression by transcription factors, such as WT1, is important for
      halting disease progression.

PMID- 16572587
TI  - Gene expression profiles of the aurora family kinases.
AB  - The evolutionarily conserved Aurora family kinases, a family of mitotic
      serine/threonine kinases, has three members in humans (Aurora-A, -B and -C).
      Overexpression of Aurora family members, particularly Aurora-A, has been reported
      in many human cancers and cell lines. In this study, we present evidence based on
      comparative gene expression analysis via quantitative RT-PCR to delineate the
      relative contributions of these kinases in 60 cell lines and statistical analysis
      in five different human cancer microarray datasets. The analysis demonstrated the
      selective upregulation of these Aurora members in various cancers. In general,
      Aurora-A exhibited the highest expression levels, with substantially decreased
      quantities of the Aurora-C transcript detected relative to Aurora-A and -B.
      Moreover, to characterize the roles of each Aurora member, which share many
      similarities, we investigated the expression profiles of the family in normal
      tissues and a panel of different phases of the HeLa cell cycle. Finally, both
      Aurora-A and -B were overexpressed in a majority of esophageal tumor tissues in
      comparison to the normal variants. Taken together, the results show that each
      Aurora member exhibits distinct expression patterns, implying that they are
      engaged in different biological processes to accomplish more elaborate cell
      physiological functions in higher organisms.

PMID- 16572588
TI  - Molecular cloning of the m-Golsyn gene and its expression in the mouse brain.
AB  - The mouse ortholog of the human GOLSYN gene, termed the m-Golsyn gene, was
      isolated and mapped to the region on mouse chromosome 15B3.2 syntenic with human
      chromosome 8q23. Three mRNA species (type la, 1b, and type 2) were produced by
      use of alternative transcription initiation points and alternative splicing
      events. The type 1 mRNAs were expressed only in the brain, whereas the type 2 was
      detected in various tissues. m-Golsyn protein was expressed in various tissues
      including the brain. Immunohistochemical study of m-Golsyn protein showed its
      prominent expression in the neuronal cells in various regions of the brain and
      strong expression in the choroid plexus ependymal cells lining the ventricles. m
      Golsyn protein was found to be homologous to syntaphilin, a regulator of synaptic
      vesicle exocytosis. These results indicate that the m-Golsyn protein may play an
      important role in intracellular protein transport in neuronal cells of the brain.

PMID- 16572589
TI  - Elucidation of stannin function using microarray analysis: implications for cell
      cycle control.
AB  - Stannin (Snn) is a highly conserved, vertebrate protein whose cellular function
      is unclear. We have recently demonstrated in human umbilical vein endothelial
      cells (HUVECs) that Snn gene expression is significantly induced by tumor
      necrosis factor-alpha (TNF-alpha) in a protein kinase C-epsilon (PKC-epsilon)
      dependent manner. In HUVEC, TNF-alpha stimulation of HUVECs results in altered
      gene expression, and a slowing or halting of cell growth. An initial set of
      experiments established that Snn knockdown via siRNA, prior to TNF-alpha
      treatment, resulted in a significant inhibition of HUVEC growth compared to TNF
      alpha treatment alone. In order to assess how Snn may be involved in TNF-alpha
      signaling in HUVEC growth arrest, we performed microarray analysis of TNF-alpha
      stimulated HUVECs with and without Snn knockdown via siRNA. The primary
      comparison made was between TNF-alpha-stimulated HUVECs and TNF-alpha-exposed
      HUVECs that had Snn knocked down via Snn-specific siRNAs. Ninety-six genes were
      differentially expressed between these two conditions. Of particular interest was
      the significant upregulation of several genes associated with control of cell
      growth and/or the cell cycle, including interleukin-4, p29, WT1/PRKC, HRas-like
      suppressor, and MDM4. These genes act upon cyclin D1 and/or p53, both of which
      are key regulators of the G1 phase of the cell cycle. Functional studies further
      supported the role of Snn in cell growth, as cell cycle analysis using flow
      cytometry shows a significant increase of G1 cell cycle arrest in HUVECs with Snn
      knockdown in response to TNF-alpha treatment. Together these studies suggest a
      functional role of Snn in regulation of TNF-alpha-induced signaling associated
      with HUVEC growth arrest.

PMID- 16572590
TI  - Ontogenetic distribution of 5-HT2C, 5-HT5A, and 5-HT7 receptors in the rat
      hippocampus.
AB  - It is known that serotonin exerts its different nociceptive and motor functions
      by interacting with distinct receptors subtypes, which could be either G-protein
      coupled or ionotropic. Previous reports demonstrated the early activation of
      serotonin receptor transcripts during rat development, suggesting a potential
      role of the serotoninergic system during ontogeny. In this study we have compared
      the cellular distribution of three serotonin receptor subtypes: 5-HT2C, 5-HT5A,
      and 5-HT7. Immunocytochemical methods were used in slices of rat hippocampus
      obtained during the postnatal development. 5-HT2c immunoreactivity was strong at
      all developmental stages in the CA1 region, whereas differences were observed
      between P0 and P5 in the CA3 region. The 5-HT5A receptor immunosignal in CA1 and
      CA3 was strong at P0, decreased at P11, and then increased in the adult. The
      immunoreactivity to 5-HT7 receptors was high in all regions at P0 and then
      decreased progressively during postnatal development; the signal was stronger for
      5-HT2c than for 5-HT5A and 5-HT7 receptors. Changes in the expression level of
      each receptor may result in differences in functional and pharmacological
      properties of the cells expressing them as well as in the hippocampal neuronal
      network. The distribution of the three serotonin receptor subtypes studied varied
      during the ontogeny, which supports their potential role during development and
      will help to understand their mechanisms.

PMID- 16572591
TI  - Rare functional variants of podocin (NPHS2) promoter in patients with nephrotic
      syndrome.
AB  - Podocin (NPHS2) is a component of the glomerular slit-diaphragm, with major
      regulatory functions in renal permeability of proteins. Loss of podocin and
      decrease in resynthesis may influence the outcome of proteinuric renal disease
      such as segmental glomerulosclerosis (FSGS), and promoter functionality plays a
      key role in this process. NPHS2 promoter variants with functional activity may be
      a part of the problem of podocin resynthesis. We sequenced NPHS2 promoter region
      from -628 to ATG in a large cohort of 260 nephrotic patients (161 with FSGS) who
      were presenting proteinuria from moderate to severe and were receiving or had
      received modular therapies according to their sensitivity to steroids and other
      immune modulators. Three sequence variants (-236C>T, -52C>G, -26C>G) were
      identified in our study population that gave an allele frequency below 1% (5
      patients out of 520 alleles). Functional implications were shown for each
      variants that were most evident for -52C>G and -26C>G (-50% of luciferase
      expression compared to the wild-type sequence, p < 0.01). Consensus analysis for
      homology of the -52 region with regulatory factors revealed homology for USF1 and
      the sum of experiments with gel retardation and with cells silenced for USF1
      confirmed that this factor regulates NPHS2 expression at this site. In
      conclusion, three functional variants in NPHS2 promoter have been identified in a
      large cohort of patients with nephrotic syndrome and FSGS that have a frequency
      <1%. One of these (i.e., -52C>G) is associated with a poor clinical outcome and
      evolution to end-stage renal failure. USF1 was identified as the transcriptional
      factor regulating NPHS2 at this site. Even if not sufficient to cause FSGS per
      se, these variants could represent modifiers for severity and/or progression of
      the disease.

PMID- 16572592
TI  - Twenty years of systemic therapy for breast cancer.
AB  - The past 2 decades of systemic therapy for breast cancer have been a period of
      monumental change, in terms of both theory and technology. Adjuvant therapy
      developed from two strands of research--one in systemic chemotherapy and one in
      hormonal therapy--both of which were aided by the application of higher
      statistical methodology to clinical trials. The agent with the single greatest
      public health impact in oncology has been tamoxifen, but problems with tamoxifen
      therapy led to the development of the aromatase inhibitors, and further research
      led to the use of hormonal therapy in a chemopreventive capacity. The evolution
      of systemic chemotherapy for breast cancer has been an interplay between theory
      driven approaches and new agents. By the late 1980s, accumulating data revealed
      that overexpression of HER2 (erbB2) played an important role in a substantial
      portion of breast cancers, which prompted the development of trastuzumab
      (Herceptin), an agent targeting HER2-positive disease. Determining HER2 status
      proved essential to assessing patient eligibility for trastuzumab therapy.
      Decoding of the human genome and application of bioinformatics further
      revolutionized the possibilities in breast cancer treatment.

PMID- 16572593
TI  - Surgical staging in endometrial cancer.
AB  - Early presentation of endometrial cancer permits effective management with
      excellent clinical outcome. The addition of hysteroscopy to dilatation and
      curettage (D&C) in the evaluation of postmenopausal bleeding adds little to the
      detection of malignancy. Imaging studies such as computed tomography, magnetic
      resonance imaging, and positron-emission tomography may be of use in determining
      the presence of extrauterine disease in patients medically unfit for surgical
      staging. However, these studies are not sufficiently sensitive to replace
      surgical staging and have little role in routine preoperative evaluation.
      Clinical staging alone is clearly inadequate, as 23% of preoperative clinical
      stage I/II patients are upstaged with comprehensive surgical staging.
      Preoperative tumor grade from D&C or office biopsy may be inaccurate and lead to
      an underestimate of tumor progression if used to determine which patients should
      be surgically staged. Clinical estimation of depth of invasion, with or without
      frozen section, is inaccurate and may lead to underestimation of disease status
      when surgical staging is not performed. The practice of resecting only clinically
      suspicious nodes should be discouraged as it is no substitute for comprehensive
      surgical staging. Comprehensive surgical staging provides proper guidance for
      postoperative adjuvant therapy, avoiding needless radiation in 85% of clinical
      stage I/II patients. Finally, resection of occult metastasis with surgical
      staging may improve survival.

PMID- 16572594
TI  - Patient-physician communication in oncology: what does the evidence show?
AB  - Effective communication between patients and oncologists is an area of active and
      growing research interest. Evidence-based recommendations can be drawn from
      studies examining (1) the patient-physician relationship; (2) how physicians
      handle medical information; (3) how physicians deal with patient emotions; (4)
      system-level communication interventions; (5) physician self-management, and (6)
      educational interventions designed to improve communication. Existing research
      provides a great deal of descriptive data about patient-oncologist communication,
      although intervention studies that link communication to patient outcomes are
      much less common.

PMID- 16572595
TI  - Gynecologic manifestations of hereditary nonpolyposis colorectal cancer. From
      inherited to sporadic disease.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer
      susceptibility syndrome associated with inherited defects in the DNA mismatch
      repair system. HNPCC family members are at high risk for developing colorectal,
      endometrial, and ovarian cancers. Studies of HNPCC families have helped define
      the important role that mismatch repair genes play in the molecular pathogenesis
      of endometrial and ovarian cancers. This review will describe some of the
      important clinical and molecular features of HNPCC-related endometrial and
      ovarian cancer and describe how genetic susceptibility can be identified in
      patients with sporadic endometrial and ovarian cancers. It is important to
      identify patients with HNPCC, as families of mutation carriers may benefit from
      genetic counseling, testing, and intensified cancer surveillance.

PMID- 16572597
TI  - Antioxidant requirements of endurance athletes: implications for health.
AB  - This review discusses studies investigating the effects of antioxidant
      supplementation on exercise-induced oxidative stress with a focus on the health
      implications. The aim is to determine antioxidant requirements for endurance
      athletes. Overall, differences in methodology make it difficult to compare the
      relatively small number of published studies on this topic. The types of studies
      needed to more adequately assess the health effects of antioxidant supplements in
      athletes (long-term interventions with hard end points) have not been done.
      Therefore, there is currently insufficient evidence to recommend antioxidant
      supplements for endurance athletes.

PMID- 16572598
TI  - The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health
      and disease.
AB  - Cocoa and chocolate have recently been found to be rich plant-derived sources of
      antioxidant flavonoids with beneficial cardiovascular properties. These favorable
      physiological effects include: antioxidant activity, vasodilation and blood
      pressure reduction, inhibition of platelet activity, and decreased inflammation.
      Increasing evidence from experimental and clinical studies using cocoa-derived
      products and chocolate suggest an important role for these high-flavanol
      containing foods in heart and vascular protection.

PMID- 16572599
TI  - Can nutrition limit exercise-induced immunodepression?
AB  - Prolonged exercise and heavy training are associated with depressed immune cell
      function. To maintain immune function, athletes should eat a well-balanced diet
      sufficient to meet their energy, carbohydrate, protein, and micronutrient
      requirements. Consuming carbohydrate during prolonged strenuous exercise
      attenuates rises in stress hormones and appears to limit the degree of exercise
      induced immune depression. Recent evidence suggests that antioxidant vitamin
      supplementation may also reduce exercise stress and impairment of leukocyte
      functions. Further research is needed to evaluate the effects of other
      antioxidants and dietary immunostimulants such as probiotics and echinacea on
      exercise-induced immune impairment.

PMID- 16572600
TI  - Synbiotic therapy: a promising new adjunctive therapy for ulcerative colitis.
AB  - Prebiotic and probiotic therapies are new strategies being used to treat
      gastrointestinal diseases. Recent evidence suggests that the administration of
      select prebiotics and probiotics, alone or in combination (the latter called
      "synbiotic" therapy) may improve the clinical outcome of patients with ulcerative
      colitis. We report a case of a pediatric ulcerative colitis patient who showed
      increased length of remission, resolution of symptoms, and improved quality of
      life following the administration of synbiotic therapy. The literature supporting
      the use of prebiotic, probiotic, and synbiotic therapies in adult ulcerative
      colitis is also reviewed.

PMID- 16572601
TI  - Too much of a good thing? Update on fish consumption and mercury exposure.
AB  - While there is a significant amount of data showing health benefits of increased
      fish consumption, there are conflicting reports about the cardiovascular risks of
      mercury in seafood. A recent long-term study attempted to resolve this
      controversy, providing an opportunity to balance recommendations from the US
      Environmental Protection Agency for mercury with those from the American Heart
      Association for fish consumption.

PMID- 16572602
TI  - Bioavailability of selenium from foods.
AB  - Selenium (Se), an essential nutrient, is needed for activity of several important
      proteins. Additionally, the consumption of Se in amounts that exceed the
      Recommended Dietary Allowance (RDA) may protect against prostate and colorectal
      cancer. Supplemental Se may be acquired through the diet, but Se bioavailability
      depends on the source. Therefore, dietary advice concerning improvement of Se
      intake depends on characterization of Se bioavailability from Se-containing food
      sources.

PMID- 16572603
TI  - Management of cerebral vascular structures during endoscopic treatment of
      encephaloceles: a clinical report.
AB  - OBJECTIVES: Otolaryngologists are increasingly being called upon to treat
      patients with cerebrospinal fluid leak and encephaloceles. The endoscopic
      approach to the skull base through the nose and paranasal sinuses has proven
      effective and is well tolerated by patients. With its more widespread and
      frequent use, unusual cases and potential complications are becoming more
      apparent. METHODS: Treatment of two clinical cases in which a cerebral vascular
      structure was encountered during endoscopic treatment of an encephalocele is
      presented, and the condition is reviewed. RESULTS: Two patients presented after a
      skull base injury that occurred during endoscopic sinus surgery. In each case the
      initial treating surgeon attempted endoscopic repair of a cerebrospinal fluid
      leak, but the repair failed and the leak persisted. Upon referral to the author,
      in each case, a traumatic encephalocele with an active leak was apparent, and
      during repair a cerebral vessel was encountered. It appeared that the vessel had
      been "pulled down" into the skull base defect with the encephalocele's migration
      into the sinonasal cavity. CONCLUSIONS: This unusual clinical condition is
      discussed along with the potential complications that can result from it.
      Otolaryngologists who treat encephaloceles should be aware of the possibility of
      encountering a cerebral vessel and should understand the potential complications
      and management options.

PMID- 16572604
TI  - Pyriform sinus mucosa stabilization for prevention of postoperative airway
      obstruction in arytenoid adduction.
AB  - OBJECTIVES: The Isshiki arytenoid adduction procedure directly closes the open
      posterior glottis. Postoperative airway obstruction that necessitates emergent
      tracheotomy is an important complication in arytenoid adduction patients when the
      standard posterior thyroplasty window is used to approach the posterolateral
      larynx. Immediate postoperative fiberoptic laryngoscopy shows ipsilateral edema
      and/or hematoma of the arytenoid and supraglottic mucosa, with occasional
      obstructing inspiratory collapse. In this study, I sought to modify the posterior
      window approach during arytenoid adduction surgery, and thereby decrease the
      incidence of immediate postoperative airway obstruction. METHODS: I performed a
      retrospective chart review of 246 arytenoid adduction patients, looking for
      immediate postoperative airway compromise. RESULTS: There were no episodes of
      postoperative airway obstruction that necessitated tracheotomy in the first 30
      patients in whom I approached the posterolateral larynx using the classic Isshiki
      techniques. Nine of the succeeding 132 adduction patients required emergent
      tracheotomy when the standard posterior window technique was used instead of a
      classic Isshiki approach (6.8%). In the most recent 84 patients, I used one
      tacking suture to stabilize the elevated pyriform sinus mucosa to the upper
      margin of the posterior window cartilage at closure. Four of the 84 patients had
      audible postoperative airway turbulence that abated with medical treatment, and 1
      patient required an emergent tracheotomy (1.2%; p = .0495). CONCLUSIONS: Suture
      stabilization of the pyriform sinus mucosa is effective and is recommended for
      prevention of posterior glottic airway obstruction after arytenoid adduction when
      the posterior window technique is used.

PMID- 16572605
TI  - Natural history of adult-onset laryngeal papillomatosis following multiple
      cidofovir injections.
AB  - OBJECTIVES: A prospective study was performed to assess the intermediate and long
      term efficacy of intralesional cidofovir therapy associated with surgical
      excision in laryngeal papillomatosis in adults. METHODS: Endoscopy with
      intralesional injection of cidofovir 5 mg/mL was performed 3 times at 4-week
      intervals. The concentration was later increased to 7.5 mg/mL and the interval
      between injections shortened to 2 weeks. Further treatment was performed at 3 or
      6 months, depending on the evolution of the papillomas. After complete remission,
      the treatment was stopped and the patients were reviewed every 6 months. RESULTS:
      Nineteen patients completed the protocol, with a mean of 4.5 injections each.
      Complete remission was obtained in 17 cases (89%) after a mean of 3.8 procedures.
      Remission was stable after a mean follow-up of 24 months (range, 8 to 57 months).
      With higher cidofovir concentrations at shorter intervals, patients needed fewer
      injections to achieve remission (mean, 2.1 versus 4.7 injections). CONCLUSIONS:
      The effectiveness of intralesional cidofovir therapy in adult-onset recurrent
      respiratory papillomatosis was impressive. Once obtained, complete remission was
      stable on intermediate or long-term follow-up. The concentration and the interval
      between injections seemed to influence the number of injections necessary to
      achieve remission.

PMID- 16572606
TI  - Virtual versus conventional laryngeal endoscopy.
AB  - We have evaluated the capacity of virtual laryngoscopy and conventional
      laryngoscopy conducted with a rigid or flexible instrument to visualize laryngeal
      structures in 64 patients with normal endoluminal anatomy. Virtual laryngoscopy
      allowed total visualization of laryngeal structures, including those that could
      not be reached by a flexible instrument. There was good correlation between
      virtual laryngoscopy and "real" images, indicating satisfactory diagnostic
      accuracy (p < .05). Although virtual laryngoscopy does not provide histologic
      data, it is a fast and noninvasive technique that can be added to and integrated
      with conventional laryngoscopy, and it can be an alternative in cases in which
      conventional laryngoscopy is difficult, contraindicated, or impossible. It is
      particularly useful for the study of laryngeal narrow spaces and in the
      visualization of subglottic regions and of other more restricted areas (inferior
      tonsil region, posterior surface of the epiglottis, glossoepiglottic vallecula,
      Morgagni's ventricle, anterior commissure).

PMID- 16572607
TI  - Penicillin resistance is not extrapolable to amoxicillin resistance in
      Streptococcus pneumoniae isolated from middle ear fluid in children with acute
      otitis media.
AB  - OBJECTIVES: We evaluated the in vitro antibacterial activity of amoxicillin
      against penicillin-susceptible and -nonsusceptible Streptococcus pneumoniae
      strains isolated from children with acute otitis media (AOM). METHODS: Children
      more than 3 months of age with AOM who were seen in the Dr Sotero del Rio and
      Luis Calvo Mackenna Hospitals in Santiago, Chile, between July 1998 and December
      2002 were subjected to tympanic puncture for middle ear fluid culture. The
      penicillin and amoxicillin susceptibilities of the S pneumoniae isolates were
      determined by epsilometer test (E test). RESULTS: A bacterial pathogen was
      isolated in 432 of 543 children (80%) as follows: S pneumoniae, 40%; Haemophilus
      influenzae, 29%; Moraxella catarrhalis, 7%; and Streptococcus pyogenes, 4%.
      Penicillin-susceptible S pneumoniae strains were less common than amoxicillin
      susceptible strains (60% versus 95%; odds ratio [OR], 0.08; 95% confidence
      interval [CI], 0.04 to 0.18). Both intermediate- and high-resistance strains were
      more common for penicillin (22% versus 4.5%; OR, 5.6; 95% CI, 2.5 to 12.7) than
      for amoxicillin (18% versus 0.5%; OR, 41.3; 95% CI, 6.0 to 821). CONCLUSIONS:
      Penicillin resistance is not extrapolable to amoxicillin among S pneumoniae
      strains isolated from middle ear fluid of children with AOM. Our results support
      the recommendation to evaluate the minimal inhibitory concentrations of
      penicillin-nonsusceptible S pneumoniae for amoxicillin and to continue use of
      this antimicrobial as a first-line antimicrobial choice for children with AOM.

PMID- 16572608
TI  - Postcricoid hemangioma of childhood: report of four cases.
AB  - Hemangiomas are the most common tumor of infancy, and the vast majority occur in
      the head and neck region. In children, laryngeal hemangiomas typically occur
      below the level of the true vocal folds, in the region of the subglottis, and
      other sites are exceedingly rare. We present four cases of hemangiomas located in
      the postcricoid region of the hypopharynx. Because of the location of these
      lesions, children may present with obstructive symptoms such as dysphagia,
      intermittent aspiration, hypersalivation, or recurrent respiratory infections.
      Clinical diagnosis is relatively easily made with flexible laryngoscopy, as the
      lesions have a propensity to enlarge with crying or straining. When these
      patients are examined under general anesthesia in a relaxed state, however, the
      lesions are typically much smaller, and can even go unnoticed. Unlike other
      reported cases, the postcricoid hemangiomas in our patients were not causing any
      symptoms and were simply incidental findings. Thus, we believe that the true
      incidence of postcricoid hemangiomas is likely higher than reports suggest. To
      our knowledge, we report the longest follow-up (6 years) of a patient with a
      postcricoid hemangioma and are the first to describe the natural course of such a
      lesion.

PMID- 16572609
TI  - Lack of association between inherited thrombophilic risk factors and idiopathic
      sudden sensorineural hearing loss in Italian patients.
AB  - OBJECTIVES: We investigated the presence of congenital thrombophilic risk factors
      in a population of consecutive Italian patients affected by idiopathic sudden
      sensorineural hearing loss (SSNHL). METHODS: We investigated 48 patients with
      idiopathic SSNHL for the presence of congenital thrombophilic risk factors. The
      factor V Leiden G1691A, the prothrombin G20210A allele, and
      methylenetetrahydrofolate reductase (MTHFR) C677T genotypes were investigated.
      Allele frequencies and genotype distribution of all factors found in patients
      were compared to those of 48 healthy subjects of the same ethnic background by
      Chi2 and odds-ratio analysis. Odds ratios and 95% confidence intervals were
      calculated for allele and genotype frequencies of all thrombophilia variants.
      Statistical significance was accepted with a p value of less than .05. We also
      performed the following blood tests: hemacytometric analysis including platelet
      count, prothrombin time, activated partial thromboplastin time, fibrinogen,
      erythrocyte sedimentation rate, C-reactive protein, protein S, protein C,
      antithrombin III, and activated protein C resistance. RESULTS: In our series, we
      did not find an association between SSNHL and abnormal levels of antithrombin
      III, protein C, protein S, D-dimer, or fibrinogen; activated protein C
      resistance; or factor V G1691A, prothrombin G20210A, or MTHFR C677T mutations.
      CONCLUSIONS: At present, the few studies regarding genetic polymorphisms of
      congenital thrombophilic factors in SSNHL are not conclusive. According to our
      data, factor V G1691A, prothrombin G20210A, and MTHFR C677T variants should be
      not considered risk factors for SSNHL. Further large prospective studies are
      needed to provide currently lacking information and to improve our knowledge in
      the field before we recommend the determination of genetic polymorphism in SSNHL
      as routine practice.

PMID- 16572610
TI  - Preoperative administration of rofecoxib versus ketoprofen for pain relief after
      tonsillectomy.
AB  - OBJECTIVES: We evaluated the analgesic efficacy and the opioid-sparing effect of
      oral rofecoxib compared with intramuscular (IM) ketoprofen in tonsillectomy.
      METHODS: Seventy-seven adult patients were randomized into 2 groups: group R (n =
      39), which received a single oral preoperative dose of rofecoxib 50 mg, and group
      K (n = 38), which received 2 IM doses of ketoprofen 100 mg (before surgery and
      after 12 hours). In both groups, additional IM meperidine hydrochloride 1 mg/kg
      was given. All patients received general anesthesia. A pain score (visual analog
      scale, 0 to 100) was assessed both at rest and during swallowing at 30 minutes
      and at 4, 8, 12, 16, and 24 hours after operation. If the pain score exceeded 40,
      patients were given meperidine as rescue analgesia. RESULTS: The pain scores
      during rest and swallowing in group R were significantly lower (p < .05) than
      those of group K at 4, 8, and 12 hours after operation. Meperidine was given as
      rescue medication in significantly more patients of group K (76%) than of group R
      (38%; p < .05). CONCLUSIONS: Oral premedication with rofecoxib seems to be more
      effective than use of ketoprofen in decreasing postoperative pain and the need
      for opioid rescue medication after elective tonsillectomy. Both drugs seem to be
      relatively safe as far as postoperative bleeding is concerned.

PMID- 16572611
TI  - Cochlear implantation in children with inner ear malformations.
AB  - OBJECTIVES: The aim of this study was to assess the outcomes of cochlear
      implantation in children with inner ear malformations (IEMs). METHODS: A
      retrospective review of 212 children who received implants from September 1994 to
      May 2004 was performed. Forty-six of them had radiologic evidence of IEMs. The
      preoperative evaluations, intraoperative findings, postoperative complications,
      and performance outcomes were analyzed. For the comparative analysis of
      performance outcomes, the children with IEMs were matched and compared with
      children with a normal inner ear who had received implants. Statistical analysis
      was performed with a repeated-measures analysis of variance. RESULTS: All of the
      children were studied with computed tomography and magnetic resonance imaging.
      Three-dimensional volume rendering of magnetic resonance images was performed in
      cases that were difficult to interpret because of structural complexity. The
      operative findings included aberrant facial nerves in 2 children and
      cerebrospinal fluid gushers in 22 children. Intraoperative fluoroscopic
      examination was performed to evaluate electrode placement. There were no serious
      postoperative complications. All children with IEMs achieved open-set speech
      perception abilities, except for the children with a narrow internal auditory
      canal (IAC), and showed progressive improvement of their speech perception
      abilities over time. There were no statistically significant differences in
      performance measured by the Common Phrases test between the 2 groups. Although
      the repeated-measures analysis of variance indicated that children with IEMs
      performed more poorly than those with a normal inner ear on the Phonetically
      Balanced Kindergarten test for phonemes, statistical significance was not found
      at 2 years after implantation. The children with a narrow IAC benefited from the
      implantation and used the device every day, although their speech perception
      abilities were limited. CONCLUSIONS: The results of the present study show that
      cochlear implantation can be performed relatively safely in deaf children with
      IEMs and that they receive considerable benefit from their implants. Substantial
      benefit can be expected from implantation in children with most kinds of IEMs,
      except for a narrow IAC, which is often associated with limited results.

PMID- 16572612
TI  - Postnatal development of rat vocal folds.
AB  - OBJECTIVES: In this study we aimed to determine the feasibility of using a rat
      model for the study of postnatal vocal fold (VF) development. METHODS: Eighteen
      male rats that were 3 days old, 3 weeks old, or 8 months old were analyzed
      histologically with Alcian blue stain used for detecting hyaluronic acid, elastin
      van Gieson stain for elastin, Oil Red O and gold chloride stains for vitamin A
      containing lipid droplets, and immunohistochemistry for vimentin (general
      fibroblast marker) and collagen types I and III. RESULTS: The macula flava (MF)
      was observed as a mass of cells that expressed vimentin intensively in the
      cytoplasm. The MF showed denser hyaluronic acid and collagen type I than did the
      midmembranous portion of the VF lamina propria. Clear developmental changes were
      evident in the MF and other regions. The vimentin-positive cells of the 3-day-old
      MF were mainly oval-shaped and had less cytoplasm, whereas those of the 8-month
      old MF were spindle- and stellate-shaped and had more cytoplasm, similar to that
      reported in humans. Vitamin A-containing lipid droplets were limited to the 3
      week-old and 8-month-old MFs and were not present in the 3-day-old VF.
      CONCLUSIONS: These results suggest that a rat model is useful in studying VF
      development and that vitamin A is related to the maturity of the VF.

PMID- 16572613
TI  - Quantitative and comparative studies of the vocal fold extracellular matrix II:
      collagen.
AB  - OBJECTIVES: This study examines the collagen content and turnover in the
      midmembranous vocal fold laminae propriae (LPs) of humans, dogs, pigs, and
      ferrets. METHODS: The LP collagen levels were assessed by quantifying tissue
      hydroxyproline. Quantitative histology allowed evaluation of the collagen content
      in specific LP regions. Several collagen types and two markers of collagen
      turnover were examined immunohistochemically. RESULTS: Collagen made up 43.4% +/-
      2.6% of human LP total protein (TP), with men having approximately 30% higher
      collagen content than women (p < .024). The collagen levels in pigs (52.6% +/-
      1.9% of TP) and ferrets (29.8% +/- 3.7% of TP), but not that in dogs (45.3% +/-
      1.2% of TP), varied significantly from that in humans (pigs, p < .016; ferrets, p
      < .011). Quantitative histology indicated marked interspecies differences in
      total collagen distribution. Collagen types I, III, and IV were detected in the
      LP, and spatially complex staining patterns were observed for the two markers of
      collagen turnover studied. CONCLUSIONS: The collagen content of the human LP is
      approximately 60% to 70% of that of human dermis. Although canine LP collagen
      levels are most similar to those of humans, quantitative histology indicates that
      the collagen distribution of the human LP is best matched by the porcine LP.
      Collagen types I and III seem to be the dominant LP collagens. Spatial variations
      in collagen turnover appear to exist that may contribute to normal LP physiology.

PMID- 16572614
TI  - Varicella-zoster virus load and cochleovestibular symptoms in Ramsay Hunt
      syndrome.
AB  - OBJECTIVES: The mechanism by which varicella-zoster virus (VZV) reactivation
      causes cochleovestibular symptoms (CVSs) in patients with Ramsay Hunt syndrome
      (RHS) remains to be elucidated. The present study analyzed the relationship
      between VZV load and the onset of CVSs in RHS. METHODS: The subjects consisted of
      56 patients with RHS; 29 exhibited CVSs and facial paralysis (FP; group 1), and
      27 exhibited FP without CVSs (group 2). The VZV DNA copy number in the saliva was
      measured with a quantitative polymerase chain reaction. Anti-VZV antibodies were
      assayed by an enzyme-linked immunosorbent assay with paired sera. RESULTS: There
      was no significant difference in maximum viral copy number between the two
      groups. In group 1, CVSs occurred at various times between the early phase and
      the regression phase of VZV reactivation. In some patients, CVSs occurred in the
      early phase of VZV reactivation, before the onset of zoster lesions and FP.
      CONCLUSIONS: There are various different patterns in the development of eighth
      cranial nerve dysfunction, which is caused by progression of neuritis or
      labyrinthitis following VZV reactivation. Our data suggest that CVSs in RHS may
      also be caused by reactivation of VZV in the spiral and/or vestibular ganglia.

PMID- 16572615
TI  - Reconstruction of the columella with bilateral nostril sill flaps.
AB  - The treatment of total columellar defects is very difficult, and there is not any
      first choice in reconstruction of these defects. Various techniques have been
      reported for this purpose. Each technique has its own drawbacks, and few can be
      performed in one stage. We report a pediatric patient with a defect involving the
      entire columella. Reconstruction of the defect was accomplished with laterally
      based bilateral nostril sill flaps. An acceptable cosmetic result was obtained.
      This method can be done as a single-stage operation with an excellent color and
      texture match. We think that this method leads to good aesthetic results, and
      should be considered for total columellar reconstruction.

PMID- 16572616
TI  - Western blot immunoassay for HSP-70 antibodies in idiopathic tinnitus: a
      preliminary report.
AB  - OBJECTIVES: Our preliminary study investigated the role of nonspecific
      immunologic tests and immunoassay for heat shock protein 70 (HSP-70) in
      supporting the possibility of an autoimmune inner ear process determining
      idiopathic tinnitus. METHODS: Thirty-six consecutive patients with idiopathic
      tinnitus without other otologic or autoimmune diseases and 20 healthy blood donor
      subjects underwent determinations of circulating immune complexes (CICs) and
      other nonspecific immunologic factors and immunoassay for HSP-70. RESULTS: The
      mean CIC values were 4.2 microg/mL in the tinnitus patients and 0.9 microg/mL in
      the control group (p = .012). Thirteen of the 36 tinnitus patients and none of
      the control group were HSP-70-positive. Ten of the 13 HSP-70-positive patients
      had CIC values higher than normal. In the tinnitus group, the mean CIC values
      were 6.9 microg/mL and 2.6 microg/mL in the HSP-70-positive and -negative
      subgroups, respectively (p = .024). CONCLUSIONS: It may be hypothesized that in a
      significant number of cases, idiopathic tinnitus could be induced by immune
      response to inner ear-specific HSP-70.

PMID- 16572617
TI  - Surgical treatment of 40 patients with thoracic ossification of the ligamentum
      flavum.
AB  - OBJECT: The authors evaluated different surgical methods used to treat thoracic
      ossification of the ligamentum flavum (OLF). METHODS: Data obtained in 40
      patients who underwent posterior decompression for thoracic myelopathy caused by
      thoracic OLF were studied retrospectively. There were 32 men and eight women. All
      patients underwent posterior decompression in which laminoplasty was performed or
      laminectomy combined with lateral fusion. Every surgical specimen was stained
      with H & E, and scanning electron microscopy was performed in 20 cases. The mean
      follow-up period was 28 months. Postoperative outcomes were evaluated using a
      recovery scale based on the Japanese Orthopaedic Association classification.
      There were a total of 168 ossified segments in this series, 77.4% of which were
      located in the lower thoracic spine. Marginal osteophyte formation was found in
      36 patients; in 32 of the 36 patients, these marginal osteophytes were located at
      the intervertebral space either higher or lower than the ossified segment.
      Scanning electron microscopy showed elastic fiber breakdown, proliferation of
      collagenous fibers, calcification, and OLF in the same microscopy region.
      Laminoplasty was performed in four patients. In three cases surgery resulted in
      unchanged or worse outcome (increased kyphotic deformity in two), and in one it
      resulted in good outcome. Laminectomy combined with lateral fusion was performed
      in 36 patients, in 30 cases of which it resulted in a good or fair outcome, and
      increased kyphotic deformity in only one. Of these 36 laminectomy-treated
      patients, an en bloc laminectomy-treated procedure was performed in 16 patients;
      in 11 of the 12 patients with lateral or diffuse-type lesions the surgery
      resulted in a good or fair outcome. En bloc laminectomy, however, seems
      ineffective in the treatment of patients with thickened, nodular-type thoracic
      OLF, as the procedure resulted in worse outcome in two of the four patients. The
      authors have thus developed a new modality of laminectomy that they have termed
      "separating laminectomy," which they performed in 16 patients with thickened,
      nodular-type OLF; in 13 cases it resulted in a good or fair outcome, and in only
      one case did it result in a worse outcome. CONCLUSIONS: The pathogenesis of
      thoracic OLF is mainly due to the localized mechanical stress on the ligament.
      Laminectomy combined with lateral fusion is the treatment of choice for thoracic
      OLF; furthermore, in terms of the configuration of the ossified lesion, en bloc
      laminectomy is suitable for the treatment of lateral-type and diffuse-type OLF,
      and the separating laminectomy is suitable for the thickened, nodular-type OLF.

PMID- 16572618
TI  - Unilateral transforaminal lumbar interbody fusion and bilateral anterior-column
      fixation with two Brantigan I/F cages per level: clinical outcomes during a
      minimum 2-year follow-up period.
AB  - OBJECT: There are no published reports of unilateral transforaminal lumbar
      interbody fusion (TLIF) in which two Brantigan I/F cages were placed per level
      through a single portal to achieve bilateral anterior-column support. The authors
      describe such a surgical technique and evaluate the clinical outcomes of this
      procedure. METHODS: Data obtained in 86 (93.5%) of the first 92 consecutive
      patients who underwent the procedure were retrospectively reviewed; the minimum
      follow-up duration was 2 years. The clinical outcomes were evaluated using the
      Japanese Orthopaedic Association (JOA) scoring system. Disc height, disc angle,
      cage positioning in the axial plane, and fusion status were radiographically
      evaluated. The mean follow-up period was 33.8 months. The mean improvement in the
      JOA score was 77.2%. Fusion was successful in 93% of the cases. According to the
      Farfan method, the mean anterior and posterior disc heights increased from 20.2
      and 16.9% preoperatively to 35.9 and 22.7% at follow up, respectively (p < 0.01).
      The mean disc angle increased from 4.8degrees preoperatively to 7.5degrees at
      last follow-up examination (p < 0.01). Two cages were correctly placed to achieve
      bilateral anterior-column support in greater than 85% of the cases. The following
      complications occurred: hardware migration in two patients and deep infection
      cured by intravenous antibiotic therapy in one patient. CONCLUSIONS: Unilateral
      TLIF involving the placement of two Brantigan cages per level led to good
      clinical results. Two Brantigan cages were adequately placed via a single portal,
      and reliable bilateral anterior-column support was achieved. Although the less
      invasive unilateral approach was used, the outcomes were as good as those in many
      reported series of posterior lumbar interbody fusion in which the Brantigan cages
      were placed via the bilateral approach.

PMID- 16572619
TI  - Biomechanical study of thoracolumbar junction fixation devices with different
      diameter dual-rod systems.
AB  - OBJECT: Advances in the design of a smaller-diameter rod system for use in the
      thoracolumbar region prompted the authors to undertake this biomechanical study
      of two different thoracolumbar implants. METHODS: In vitro biomechanical testing
      was performed using human cadaveric spines. All specimens were loaded to a
      maximum moment of 5 Nm with 300-N axial preload in six modes of motion. Two types
      of anterior implants with different rod diameters were applied to intact T10-12
      specimens in two groups. The loading was repeated and the range of motion (ROM)
      was measured. A T-11 corpectomy was then performed and a strain gauge-mounted
      carbon fiber stackable cage was implanted. The ROM and compression force on the
      cage were measured, and the mean values were compared between these two groups.
      With stabilization of the intact spine, ROM decreased least in extension and
      greatest in bending compared with the intact specimens. After corpectomy and
      stabilization, ROM increased in extension by 104.89 +/- 53.09% in specimens with
      a 6.35-mm rod insertion and by 83.81 +/- 16.96% in those with a 5.5-mm rod,
      respectively; in flexion, ROM decreased by 26.98 +/- 27.43% (6.35 mm) and by 9.59
      +/- 15.42% (5.5 mm), respectively; and in bending and rotation, both groups each
      showed a decrease in ROM. The load sharing of the cage was similar between the
      two groups (the 6.35-mm compared with 5.5-mm rods): 47.44 and 44.73% (neutral),
      49.16 and 39.02% (extension), 61.90 and 56.88% (flexion), respectively.
      CONCLUSIONS: There were no statistical differences in the ROM and load sharing of
      the cage when either the 6.35-or 5.5-mm-diameter dual-rod was used.

PMID- 16572620
TI  - A biomechanical comparison of three anterior thoracolumbar implants after
      corpectomy: are two screws better than one?
AB  - OBJECT: A flexibility experiment using human cadaveric thoracic spine specimens
      was performed to determine biomechanical differences among thoracolumbar two
      screw plate, single-screw plate, and dual-rod systems. A secondary goal was to
      investigate differences in the ability of the systems to stabilize the spine
      after a one- or two-level corpectomy. METHODS: The authors evaluated 21 cadaveric
      spines implanted with a titanium mesh cage and three types of anterior
      thoracolumbar supplementary instrumentation after one-level thoracic
      corpectomies. Pure moments were applied quasistatically while three-dimensional
      motion was measured optoelectronically. The lax zone, stiff zone, and range of
      motion (ROM) were measured during flexion, extension, left and right lateral
      bending, and left and right axial rotation. Corpectomies were expanded to two
      levels, and testing was repeated with longer hardware. Biomechanical testing
      showed that the single-bolt plate system was no different from the dual-rod
      system with two screws in limiting ROM. The single-bolt plate system performed
      slightly better than the two-screw plate system. Across the same two levels,
      there was an average of 19% more motion after a two-level corpectomy than after a
      one-level corpectomy. In general, however, the difference across the different
      loading modes was insignificant. CONCLUSIONS: Biomechanically, the single-screw
      plate system is equivalent to a two-screw dual-rod and a two-screw plate system.
      All three systems performed similarly in stabilizing the spine after one- or two
      level corpectomies.

PMID- 16572621
TI  - Biomechanical evaluation of the ventral and lateral surface shear strain
      distributions in central compared with dorsolateral placement of cages for lumbar
      interbody fusion.
AB  - OBJECT: The purpose of this study was to measure and compare the ventral and
      lateral surface strain distributions and stiffness for two types of interbody
      cage placement: 1) central placement for anterior lumbar interbody fusion (ALIF);
      and 2) dorsolateral placement for extraforaminal lumbar interbody fusion (ELIF).
      METHODS: Two functional spine units were obtained for testing in each of 13
      cadaveric spines, yielding 26 segments (three of which were not used because of
      bone abnormalities). Bilateral strain gauges were mounted adjacent to the
      endplate on the lateral and ventral walls of each vertebral body in the 23 motion
      segments. Each segment was cyclically tested in compression, flexion, and
      extension in the following conditions: while intact, postdiscectomy, and
      instrumented with interbody fusion cages placed using both insertion techniques.
      No significant differences were observed between ALIF and ELIF in compressive
      stiffness, bending stiffness in flexion and extension (p > or = 0.1), ventral and
      lateral strain distribution during the intact tests (p > or = 0.24), and during
      the flexion tests after fusion (p > or = 0.22). In compression, higher ventral
      and lower lateral strain was observed in the ALIF than in the ELIF group
      (ventral, p = 0.05; lateral, p = 0.04), and in extension, higher ventral (p =
      0.01) and higher lateral strain (p = 0.002) was observed in the ELIF than in the
      ALIF group. CONCLUSIONS: Preservation of the ventral anulus and dorsolateral
      placement of the interbody cages during ELIF allow alternate load transfer
      pathways through the dorsolateral vertebral wall and ventral anulus that are not
      observed following ALIF. These may be associated with a lower incidence of
      subsidence and a higher rate of fusion due to a more concentrated application of
      bone healing-enhancing compression forces during the fusion and healing process.

PMID- 16572622
TI  - Anatomical feasibility of using the ninth, 10th, and 11th intercostal nerves for
      the treatment of neurological deficits after damage to the spinal cord.
AB  - OBJECT: The topographic anatomy of the lower intercostal nerves is less well
      known than that of the upper ones, except for the 12th intercostal nerve. It is
      possible to use the lower intercostal nerves to perform a neurotization of the
      lumbar roots. The authors studied the anatomy of the ninth, 10th, and 11th
      intercostal nerves to obtain descriptive and topographic anatomical data to aid
      in establishing optimal conditions for harvesting. METHODS: The ninth, 10th, and
      11th intercostal nerves of 50 cadavers were dissected. The proximal part of the
      nerve in the posterior intercostal space (ISC) was exposed through a posterior
      approach. The lateral ICS was exposed through a lateral approach, under the
      latissimus dorsi, which made it possible to harvest the intercostal nerves using
      a stripping technique. A histological study was conducted on 10 pigs to evaluate
      the risk of nerve lesions during the stripping procedure. CONCLUSIONS: The
      proximal course of the nerve in the posterior ICS was the same in all cases. The
      mean total length of the intercostal nerves harvested was 17.96 cm for the ninth,
      17.14 cm for the 10th, and 15.94 cm for the 11th intercostal nerve. The harvested
      nerve length was sufficient in 297 of the 300 cases to perform lumbar root
      neurotization. The histological study showed no difference between the "open" and
      the "stripping" techniques regarding the risk of histological lesions in
      harvested nerves.

PMID- 16572623
TI  - Spinal cord injury-induced expression of the immune-regulatory chemokine
      interleukin-16 caused by activated microglia/macrophages and CD8+ cells.
AB  - OBJECT: Spinal cord injury (SCI) elicits a strong inflammatory response that
      readily participates in lipid oxygenation, edema formation, apoptotic cell death,
      and tissue remodeling. Because cytokines determine the postinjury inflammatory
      milieu, the authors analyzed the expression of the immunomodulatory chemokine
      interleukin- 16 (IL- 16) after SCI. METHODS: The authors detected a highly
      significant, persistent, lesional accumulation of parenchymal IL-16+
      microglia/macrophages, which reached a maximal level 3 days postinjury compared
      with control rats. The majority of cells that demonstrated positive labeling for
      IL-16 also had positive labeling for ED1 (> 70%) and OX-8/CD8; these cells
      exhibited the morphological hallmarks of activated microglia/macrophages and
      pronounced MHC Class II expression. In contrast to IL-16+ED1+ cells, IL-16+
      microglia/macrophages that coexpressed OX-8 were exclusively seen in the
      pannecrotic lesion core. In addition, clustering of IL-16+ cells was observed in
      perivascular Virchow-Robin-like spaces in areas of the primary injury (lesion
      core) and in immediately adjacent areas of secondary injury. Furthermore, on Day
      3 postinjury, IL-16+ microglia/macrophages were frequently observed in a
      perineuronal position. CONCLUSIONS: The early lesional accumulation of IL-16+
      microglia/macrophages suggests a role for IL-16 in the early postinjury immune
      response such as recruitment and activation of immune cells, leading to
      microvessel clustering and secondary damage progression.

PMID- 16572624
TI  - Spinal dural arteriovenous fistula associated with a spinal perimedullary
      fistula: case report.
AB  - Among spinal cord vascular malformations, dural arteriovenous fistulas (DAVFs)
      must be distinguished from intradural malformations. The concurrence of both is
      extremely rare. The authors report the case of a 35-year-old man who suffered
      from progressive myelopathy and who harbored both a DAVF and an intradural
      perimedullary fistula. During surgery, both fistulas were identified, confirmed,
      and subsequently obliterated. The fistulas were located at two levels directly
      adjacent to each other. Although the incidence of concurrent spinal DAVFs is
      presumed to be approximately 2%, the combination of a dural and an intradural
      fistula is exceedingly rare; only two other cases have been reported in the
      literature. One can speculate whether the alteration in venous drainage caused by
      the (presumably congenital) perimedullary fistula could possibly promote the
      production of a second dural fistula due to elevated pressure with concomitant
      venous stagnation and subsequent thrombosis. The authors conclude that despite
      the rarity of dual pathological entities, the clinician should be aware of the
      possibility of the concurrence of more than one spinal fistula in the same
      patient.

PMID- 16572625
TI  - Sacral epithelioid angiosarcoma associated with a bleeding diathesis and spinal
      epidural hematoma: case report.
AB  - Epithelioid angiosarcoma of bone is a rare, high-grade lesion that is highly
      vascular and can be associated with a bleeding diathesis. An association has been
      reported in angiosarcomas in other locations with coagulopathy from tumor-related
      disseminated intravascular coagulopathy and fibrinolysis. The authors report the
      case of a rare occurrence of a primary sacral epithelioid angiosarcoma associated
      with a large epidural hematoma and a severe bleeding diathesis. A 25-year-old
      woman presented with weakness, fatigue, neck and low-back pain, and progressive
      left S-1 radiculopathy. Imaging studies revealed a large ventral epidural
      hematoma extending from the sacral region rostrally to C-2 and a vascular tumor
      located in the sacrum. The patient underwent a sacral laminectomy, complicated by
      postoperative bleeding from the wound, and required massive transfusions.
      Ultimately, multimodal therapy was required to obtain hemostasis, including the
      use of endovascular embolization, radiation therapy, and an infusion of epsilon
      aminocaproic acid with heparin. This case represents the first report of a
      primary epithelioid angiosarcoma in the sacrum and emphasizes that the
      coagulopathy seen in angiosarcoma is also a feature of this epithelioid variant.

PMID- 16572626
TI  - Expansive duraplasty for the treatment of spinal extradural arachnoid cysts: case
      report.
AB  - The authors report the case of a 25-year-old man with a thoracolumbar extradural
      arachnoid cyst who underwent expansive duraplasty. Symptoms, preoperative
      magnetic resonance imaging features, and intraoperative findings suggested the
      involvement of entrapment neuropathy in the manifestation of symptoms. To the
      authors' knowledge, this case represents the first evidence that expansive
      duraplasty can achieve complete resolution of the symptoms in a patient with a
      spinal extradural arachnoid cyst. The results indicate that duraplasty may be an
      alternative option in cases in which complete resection of the lesion is
      difficult and widening of the dural sac is necessary at surgery.

PMID- 16572627
TI  - Thoracic ossified meningioma and osteoporotic burst fracture: treatment with
      combined vertebroplasty and laminectomy without instrumentation: case report.
AB  - Although spinal meningioma is a common benign neoplasm, the ossified variant is
      rare. No more than 20 sporadic cases were reported in the literature between 1977
      and January 2005. Recently, the authors treated a patient with a symptomatic
      ossified meningioma located in the posterior aspect of T-11 and an associated
      osteoporotic T-11 burst fracture. The tumor was completely removed by T10-11
      laminectomy and transpedicular vertebroplasty was performed. The kyphotic
      deformity of the T-11 burst fracture was partially reduced and maintained for at
      least 2 months after vertebroplasty and laminectomy. The clinical presentation
      and management of this case are reported.

PMID- 16572628
TI  - Benign fibrous histiocytoma of the thoracic spine: case report and review of the
      literature.
AB  - Benign fibrous histiocytoma (BFH) is a rare skeletal tumor, accounting for
      approximately 1% of all surgically managed benign bone tumors. Spinal location is
      very rare, and its management can be challenging, involving excision of tumor and
      spinal reconstruction and stabilization. The prognosis is good after treatment.
      The authors present the case of BFH involving the thoracic spine and a review of
      the literature concerning BFH of the spine.

PMID- 16572629
TI  - Conus medullaris syndrome without lower-extremity involvement in L-1 burst
      fractures: report of four cases.
AB  - Conus medullaris injury from burst fractures is known to occur in conjunction
      with other neurological deficits, including lower-extremity motor weakness or
      sensory changes. Rarely does an isolated conus medullaris injury occur from an
      extradural cause without other neurological deficits. The authors report four
      cases of L-1 burst fractures in which conus medullaris dysfunction was the sole
      neurological injury in the absence of lower-extremity involvement.

PMID- 16572630
TI  - Repeated fracture of a vertebral body after treatment with balloon kyphoplasty:
      case illustration.

PMID- 16572631
TI  - What we don't (but should) know about hydrocephalus.
AB  - In an effort to identify critical gaps in the prevailing knowledge of
      hydrocephalus, the authors formulated 10 key questions. 1) How do we define
      hydrocephalus? 2) How is cerebrosinal fluid (CSF) absorbed normally and what are
      the causes of CSF malabsorption in hydrocephalus? 3) Why do the ventricles dilate
      in communicating hydrocephalus? 4) What happens to the structure and function of
      the brain when it is compressed and stretched by the expanding ventricles? 5)
      What is the role of cerebrovenous pressure in hydrocephalus? 6) What causes
      normal-pressure hydrocephalus? 7) What causes low-pressure hydrocephalus? 8) What
      is the pathophysiology of slit ventricle syndrome? 9) What is the
      pathophysiological basis for neurological impairment in hydrocephalus, and to
      what extent is it reversible? 10) How is the brain of a child with hydrocephalus
      different from that of a young or elderly adult? Rigorous answers to these
      questions should lead to more effective and reliable treatments for this
      disorder.

PMID- 16572632
TI  - Use of multifocal visual evoked potential tests in the objective evaluation of
      the visual field in pediatric epilepsy surgery.
AB  - OBJECT: To evaluate objectively the visual fields of patients with pediatric
      epilepsy who are uncooperative with perimetry and in whom postoperative visual
      field deficits are expected, the authors investigated the usefulness of the
      multifocal visual evoked potential (VEP) method. METHODS: Normal waves in
      multifocal VEP were determined in 21 healthy children (21 eyes) 6 to 15 years of
      age (mean 11.4 years). Responses from eight sites in each child were divided into
      four quadrants (superior and inferior temporal and superior and inferior nasal).
      In each quadrant, two response waves were grouped and averaged. The peak latency
      and amplitude at approximately 100 msec were used for assessment. In three cases
      involving patients with epilepsy, multifocal VEP measurements were also recorded
      and compared with the peak latency and amplitude in the healthy children. In
      these children, no significant differences were observed in the peak latency of
      amplitude among four quadrants using one-way analysis of variance. In each
      patient, multifocal VEP tests showed abnormal waves in the quadrant corresponding
      to the lesion demonstrated in neuroradiological images. This result was useful in
      the treatment of choice and the postoperative evaluation. CONCLUSIONS: Multifocal
      VEP tests can be useful in evaluating the visual field of children objectively.
      They can also be valuable in assessing preoperative visual field defects and
      revealing changes in the visual field after treatment.

PMID- 16572633
TI  - Cervicomedullary decompression for foramen magnum stenosis in achondroplasia.
AB  - OBJECT: Achondroplasia is the most common hereditary form of dwarfism, and is
      characterized by short stature, macrocephaly, and a myriad of skeletal
      abnormalities. In the pediatric population, stenosis and compression at the level
      of the cervicomedullary junction commonly occurs. The goal in this study was to
      assess the outcomes in children with achondroplasia who underwent
      cervicomedullary decompression. METHODS: Forty-three pediatric patients with
      heterozygous achondroplasia and foramen magnum stenosis underwent 45
      cervicomedullary decompressions at the authors' institution over an 11-year
      period. After surgical decompression, complete resolution or partial improvement
      in the preoperative symptoms was observed in all patients. There were no deaths
      in the treated patients. The surgical morbidity rate was low and usually
      consisted of a cerebrospinal fluid (CSF) leak in patients in whom the dura mater
      had been opened (either intentionally or accidentally). This problem was
      successfully managed in all cases with local measures (wound oversewing) or CSF
      diversion. CONCLUSIONS: In this review the authors demonstrate that decompression
      of the cervicomedullary junction in the setting of achondroplasia may be
      accomplished safely with significant clinical benefit and minimal morbidity.

PMID- 16572634
TI  - C-kit gene mutation: common and widely distributed in intracranial germinomas.
AB  - OBJECT: Of the intracranial germ cell tumors (IGCTs), 10% of germinomas and most
      nongerminomatous tumors remain refractory to multimodality therapy. The authors
      investigated the mutation of c-kit and the expression of its product KIT in IGCTs
      to identify tumors susceptible to imatinib mesylate, a synthetic agent targeting
      KIT. METHODS: The authors investigated 26 IGCTs, including 13 germinomas, five
      mixed germ cell tumors (MGCTs), four immature teratomas (ITs), and two each of
      yolk sac tumors and choriocarcinomas. These tumors were examined for the
      expression of KIT and CD34 by immunohistochemical analysis, and for mutations in
      exons 2, 8 to 11, 13, and 17 of c-kit. Strong KIT expression was found in the
      cell membrane of germinomas (100%) and germinomatous cells of MGCTs (80%), as
      well as in the cytoplasm of epithelial and smooth-muscle cells of ITs. The
      membranous expression of CD34 was found in the nongerminomatous tumor cells and
      the chondrocytes of MGCTs (60%), ITs (100%), and a choriocarcinoma (50%), but not
      in germinomas and germinomatous cells. A total of five missense mutations
      distributed in exons 2, 11, 13, and 17 of c-kit were detected in three (23%) of
      the 13 germinomas. The novel mutations E73K, T96M (both in exon 2), and A636V (in
      exon 13) were detected in a single tumor. The presence or type of c-kit mutation
      was not correlated with patient prognosis. CONCLUSIONS: Immunohistochemical
      analysis of KIT expression is useful for the diagnosis of germinoma. This study
      may help in clarifying the pathogenesis of IGCTs and in identifying tumors
      susceptible to drugs targeting KIT.

PMID- 16572635
TI  - Multilevel cervical disconnection syndrome: initial description, embryogenesis,
      and management. Report of two cases.
AB  - Two cases of a previously undescribed cervical spinal anomaly distinct from
      cervical spondylolysis are presented. The authors report the first detailed
      description of a congenital vertebral anomaly characterized by multilevel
      cervical spondylolysis, sagittal deformity, and spinal cord compression. The sine
      qua non of the condition is a lack of communication between the anterior and
      posterior columns of the cervical spinal canal, which may occur over several
      vertebral levels. A kyphotic deformity of the anterior column occurs, whereas the
      posterior column may have relatively normal alignment. The underlying
      biomechanical stresses caused by the anterior-posterior column disconnection
      result in spinal instability and progressive kyphotic deformity, often to a
      profound degree. Two children, 2 and 3 years of age, presented with congenital
      multilevel disconnection and myelopathy. In the first stage of treatment, each
      underwent an anterior decompression, reduction, and reconstruction of the
      involved segments. This was followed by posterior stabilization and fusion as a
      separate procedure. In both patients, the myelopathy improved and a solid,
      circumferential fusion was achieved. The authors' success in treating these
      patients indicates that management of these conditions can be based on the
      principles of deformity correction, spinal cord decompression, and combined
      anterior-posterior arthrodesis.

PMID- 16572636
TI  - Capillary hemangioma of the fourth ventricle in an infant. Case report and review
      of the literature.
AB  - A 3-month-old boy presented to the pediatric neurosurgery service with central
      hypotonia. Magnetic resonance images of the brain revealed a homogeneously
      enhancing dumbbell-shaped mass located in the fourth ventricle and extending into
      the left cerebellopontine angle (CPA). A suboccipital craniotomy was performed
      and a gross-total resection of the mass was achieved. Pathological examination of
      the resected tissue confirmed the diagnosis of capillary hemangioma. To the
      authors' knowledge, this is the first reported case of a capillary hemangioma
      occurring in this location. The authors provide a review of the current
      literature on intracranial capillary hemangiomas and conclude that, despite the
      rarity of these lesions, they should be considered in the differential diagnosis
      of lesions in the fourth ventricle and/or the CPA in children.

PMID- 16572637
TI  - Transient ventriculomegaly in a child presenting with hypernatremia. Case report.
AB  - The authors present the case of a 3-year-old girl with a history of
      myelomeningocele repair, ventriculoperitoneal (VP) shunt placement for
      hydrocephalus, and shaken baby syndrome who presented in a hypernatremic state as
      a result of dehydration. At the time of presentation, the patient had experienced
      a 1-week-long history of diarrhea associated with antibiotic agents used to treat
      a coexisting pyelonephritis. On admission, the patient exhibited signs and
      symptoms of dehydration and was discovered to have profound hypernatremia with a
      serum sodium level of 180 mmol/L. A computerized tomography (CT) scan of the head
      revealed ventricular enlargement compared with previous imaging findings. A shunt
      tap revealed intracranial hypotension with good proximal flow. The child was
      treated for her hypernatremic state, and her neurological condition returned to
      baseline level. Subsequent CT scans of the head demonstrated a return of the
      ventricular system to its premorbid size. On the basis of the initial
      radiographic presentation and subsequent evaluation, the authors hypothesize that
      the ventricular enlargement was a result of hypernatremia. The signs and symptoms
      were similar to those found in patients with a VP shunt obstruction; however, a
      shunt tap revealed intracranial hypotension and excellent proximal flow. To the
      authors' knowledge, there has not been a radiographically documented case of
      reversible ventricular enlargement associated with hypernatremia.

PMID- 16572638
TI  - Using the superior sagittal sinus for emergency venous access in an infant. Case
      report.
AB  - Emergency venous access in an infant suffering from multiple trauma and shock can
      be difficult. Peripheral venous access and central line placement are not always
      successful. Death following underresuscitation due to the lack of adequate access
      occurs, although it is not often reported in the literature. The author presents
      a case in which successful resuscitation was achieved by injecting blood into the
      superior sagittal sinus through an open fontanelle in a 2-week-old infant who
      presented in shock and with ventricular fibrillation after nonaccidental trauma.

PMID- 16572639
TI  - Late closure of the stoma by spreading of a periaqueductal glioma: an unusual
      failure of endoscopic third ventriculostomy. Case report.
AB  - The late failure of endoscopic third ventriculostomies (ETVs) has been described
      as a consequence of scarring phenomena involving the third ventricular floor.
      Although the possibility of closure of the stoma by intraventricular tumor
      seeding has been hypothesized, no case of ETV failure caused by tumor diffusion
      has been reported in the literature. The authors report on a 19-year-old patient,
      affected by obstructive hydrocephalus associated with a periaqueductal pilocytic
      astrocytoma, who underwent late secondary lesional obstruction of an ETV
      performed at diagnosis. The authors suggest tumor extension along the
      diencephalic neural pathways as the possible cause of ETV failure in this
      patient.

PMID- 16572640
TI  - Factor X deficiency presenting as a pseudotumor. Case report.
AB  - The authors report their experience in successfully treating a 15-week-old child
      who became comatose following a spontaneous intracerebral hemorrhage. It was
      initially believed that a tumor in the right frontal lobe caused the hemorrhage.
      Coagulation studies revealed abnormal results on presentation, and the problem
      was only partially corrected after an infusion of fresh frozen plasma. The child
      underwent an emergency craniotomy in which the hematoma was evacuated, and a
      biopsy specimen was obtained from a firm mass at the base of the hematoma cavity.
      Postoperatively, the child recovered completely, and an analysis of detailed
      coagulation studies revealed that the child had a factor X deficiency.
      Histological analysis of the biopsy specimen revealed normal brain tissue with
      hemorrhagic infiltration. Subsequently, the child achieved normal developmental
      milestones. A diagnosis of congenital bleeding disorder should be considered in
      children with spontaneous intracerebral hemorrhage, even in those with no prior
      episode of extracerebral spontaneous hemorrhage.

PMID- 16572641
TI  - Development of syringohydromyelia associated with Dandy-Walker malformation:
      treatment with cystoperitoneal shunt placement. Case report.
AB  - Dandy-Walker malformation (DWM) is a well-described clinical entity, which
      includes vermian agenesis, posterior fossa cysts, and frequently, hydrocephalus.
      The authors report the clinical course and present the radiographic findings
      pertaining to a 1-month-old girl with DWM who was treated initially with a
      ventriculoperitoneal shunt and endoscopic fenestration of a posterior fossa cyst.
      After decompression for hydrocephalus, an increased mass effect at the foramen
      magnum from her posterior fossa cyst was demonstrated, as well as subsequent
      development of syringohydromyelia from C-4 to T-7. She was treated with a
      cystoperitoneal shunt. At the 6-month follow-up examination, the child (15 months
      of age) had achieved gains in developmental milestones, and complete resolution
      of the syrinx was established through MR imaging. This is the fourth nonautopsy
      pediatric case of DWM-associated syringohydromyelia reported in the literature
      and the third in a child to demonstrate impaction of the posterior fossa cyst at
      the foramen magnum leading to syrinx formation with subsequent treatment and
      resolution. Spinal imaging may be useful in the evaluation of patients with DWM
      who do not experience expected improvement after shunt procedures.

PMID- 16572642
TI  - Posterior spinal cord herniation into an extradural thoracic arachnoid cyst:
      surgical treatment. Case report and review of the literature.
AB  - The authors describe the case of a 2-year-old boy who experienced progressive
      spastic paraparesis for several months. Magnetic resonance imaging revealed an
      extensive extradural arachnoid cyst at the T3-L1 levels and posterior spinal cord
      herniation at T3-4. Surgical release of the neck of the hernia and total
      resection of the arachnoid cyst were performed. The patient had good clinical
      recovery several weeks after surgical decompression. This case highlights an
      exceedingly rare type of spinal cord herniation in a pediatric age group, and
      focuses on the abnormalities of the dorsal dura mater, together with imaging and
      intraoperative findings.

PMID- 16572643
TI  - Cervical spinal cord compression in chondrodysplasia punctata. Case illustration.

PMID- 16572644
TI  - Clip ligation or coil occlusion?

PMID- 16572645
TI  - Treatment of ruptured intracranial aneurysms since the International Subarachnoid
      Aneurysm Trial: practice utilizing clip ligation and coil embolization as
      individual or complementary therapies.
AB  - OBJECT: The aim of this study was to analyze the therapeutic decision-making
      process and outcome in 100 consecutive patients with aneurysmal subarachnoid
      hemorrhage (SAH) treated since the completion of the International Subarachnoid
      Aneurysm Trial (ISAT). All patients were evaluated and treated by a neurosurgeon
      with subspecialty training in both cerebrovascular and neuroendovascular surgery.
      METHODS: One hundred consecutive patients with aneurysmal SAH who had been
      admitted within 1 week posthemorrhage and who had been treated using either
      surgical clip application or endovascular coil embolization were included in this
      analysis. All patients underwent a uniform perioperative protocol. All surviving
      patients were given a questionnaire to assess their modified Rankin Scale score
      (mRS) and to grade themselves at 6 months and 1 year postintervention. The cohort
      consisted of 73 women and 27 men with a mean age of 57.27 years (range 27-87
      years). Twenty-nine percent of the patients had a World Federation of
      Neurosurgical Societies (WFNS) Grade IV or V SAH. Forty-seven patients underwent
      direct surgical clip application, 41 endovascular embolization, and 12 a
      combination of the two procedures. Good functional outcome--indicated by mRS
      scores of 0 to 2 after at least 6 months--was achieved in 71% of patients.
      CONCLUSIONS: Data from the ISAT demonstrated a better functional outcome
      following endovascular embolization in a selected group of patients with
      aneurysmal SAH. In routine clinical practice, however, a significant number of
      patients still benefit from direct surgical clip ligation. Excellent functional
      results can be realized in a complementary clip ligation and coil occlusion
      practice in which each patient and aneurysm is evaluated and the two treatment
      modalities are used individually or, when needed, in combination.

PMID- 16572646
TI  - Pain in neurosurgically treated patients: a prospective observational study.
AB  - OBJECT: This is the first observational study to compare perioperative pain
      character and intensity in patients undergoing different types of elective
      neurosurgical procedures. METHODS: A structured questionnaire was used to inquire
      about pain intensity, character, and management during the perioperative course,
      and the anticipated visual analogue scale (VAS) score in 649 patients during a 1
      year period. The anticipated maximal postoperative VAS score was lower than the
      actual postoperative maximal VAS score and was independent of operation type and
      preoperative VAS score. Patients undergoing craniotomy experienced less pain than
      those undergoing spinal surgery. A majority of patients did not receive analgesic
      medication after surgery. Patients undergoing spinal surgery experienced higher
      preoperative VAS scores than those undergoing other neurosurgical treatments,
      with a shift from preoperative referred pain to postoperative local pain. After
      lumbar flavectomy, referred pain was greater than local pain. Patients with
      preoperative pain suffered significantly more postoperative pain than those
      without preoperative pain. In patients with postoperative surgery-related
      complications, VAS scores were higher than in those without complications.
      CONCLUSIONS: Neurosurgical procedures cause more pain than anticipated.
      Anticipated pain intensity is independent of the operation type and preoperative
      pain intensity. Postcraniotomy on-demand analgesic medication is appropriate, if
      the nurses on the ward react quickly. Otherwise, patient-controlled analgesia
      might be an option. Other neurosurgical procedures require scheduled analgesic
      therapies. Spinal surgery requires intensive preoperative pain treatment; a shift
      in pain character from preoperative referred pain to postoperative local pain is
      expected. Patients with referred pain after lumbar flavectomy are prone to the
      most intense pain. Patients with preoperative pain experience more postoperative
      pain than those without preoperative pain and require more intensive pain
      management. Increased postoperative VAS scores are associated with surgery
      related complications.

PMID- 16572647
TI  - Effectiveness of neuronavigation in resecting solitary intracerebral contrast
      enhancing tumors: a randomized controlled trial.
AB  - OBJECT: The goal of this study was to assess the impact of neuronavigation on the
      cytoreductive treatment of solitary contrast-enhancing intracerebral tumors and
      outcomes of this treatment in cases in which neuronavigation was preoperatively
      judged to be redundant. METHODS: The authors conducted a prospective randomized
      study in which 45 patients, each harboring a solitary contrast-enhancing
      intracerebral tumor, were randomized for surgery with or without neuronavigation.
      Peri- and postoperative parameters under investigation included the following:
      duration of the procedure; surgeon's estimate of the usefulness of
      neuronavigation; quantification of the extent of resection, determined using
      magnetic resonance imaging; and the postoperative course, as evaluated by
      neurological examinations, the patient's quality-of-life self-assessment,
      application of the Barthel index and the Karnofsky Performance Scale score, and
      the patient's time of death. The mean amount of residual tumor tissue was 28.9%
      for standard surgery (SS) and 13.8% for surgery involving neuronavigation (SN).
      The corresponding mean amounts of residual contrast-enhancing tumor tissue were
      29.2 and 24.4%, respectively. These differences were not significant. Gross-total
      removal (GTR) was achieved in five patients who underwent SS and in three who
      underwent SN. Median survival was significantly shorter in the SN group (5.6
      months compared with 9 months, unadjusted hazard ratio = 1.6); however, this
      difference may be attributable to the coincidental early death of three patients
      in the SN group. No discernible important effect on the patients' 3-month
      postoperative course was identified. CONCLUSIONS: There is no rationale for the
      routine use of neuronavigation to improve the extent of tumor resection and
      prognosis in patients harboring a solitary enhancing intracerebral lesion when
      neuronavigation is not already deemed advantageous because of the size or
      location of the lesion.

PMID- 16572648
TI  - The impact of hypotension due to the trigeminocardiac reflex on auditory function
      in vestibular schwannoma surgery.
AB  - OBJECT: Surgical manipulation of the fifth cranial nerve during its intra- or
      extracranial course may lead to bradycardia or even asystole as well as arterial
      hypotension, a phenomenon described as the trigeminocardiac reflex (TCR). The
      authors studied the impact of this reflex on postoperative auditory function in
      patients undergoing vestibular schwannoma (VS) surgery. METHODS: One hundred
      patients scheduled for VS surgery were studied prospectively for parameters
      influencing the postoperative auditory function. The evaluation included sex,
      age, pre- and postoperative auditory function, preoperative mean arterial blood
      pressure, preoperative medical diseases or medication (for example,
      antiarrhythmia drugs), tumor size and localization, and the intraoperative
      occurrence of the TCR. The TCR, which occurred in 11% of the patients, influenced
      the postoperative hearing function in the patients with Hannover Class T3 and T4
      VSs. With an overall hearing preservation of 47%, 11.1% of the patients in the
      TCR group and 51.4% of those in the non-TCR group experienced preserved hearing
      function postoperatively. In cases involving larger tumors (Hannover Class T3 and
      T4), an intraoperative TCR was associated with a significantly worse
      postoperative hearing function during VS surgery (p = 0.005). CONCLUSIONS: The
      hypotension following TCR is a negative prognostic factor for hearing
      preservation in patients undergoing VS surgery. Patients' knowledge of this can
      be increased pre- and postoperatively. Further study of this phenomenon will
      advance the understanding of the underlying mechanisms and may help to improve
      hearing preservation by controlling the occurrence of the TCR.

PMID- 16572649
TI  - Coexistence of intracranial and spinal cavernous malformations: a study of
      prevalence and natural history.
AB  - OBJECT: The purpose of this study was to examine the prevalence of intracranial
      cavernous malformations (CMs) in a large series of predominantly Caucasian
      patients with spinal cord CMs. The authors also studied the natural history of
      spinal CMs in patients who were treated nonoperatively. METHODS: The medical
      records of 67 consecutive patients (32 female and 35 male patients) in whom a
      spinal CM was diagnosed between 1994 and 2002 were reviewed. The patients' mean
      age at presentation was 50 years (range 13-82 years). Twenty-five patients
      underwent resection of the lesion. Forty-two patients in whom the spinal CM was
      diagnosed using magnetic resonance (MR) imaging were followed expectantly. Thirty
      three (49%) of 67 patients underwent both spinal and intracranial MR imaging. All
      available imaging studies were reviewed to determine the coexistence of an
      intracranial CM. Fourteen (42%) of the 33 patients with spinal CMs who underwent
      intracranial MR imaging harbored at least one cerebral CM in addition to the
      spinal lesion. Six (43%) of these 14 patients did not have a known family history
      of CM. Data obtained during the long-term follow-up period (mean 9.7 years, total
      of 319 patient-years) were available for 33 of the 42 patients with a spinal CM
      who did not undergo surgery. Five symptomatic lesional hemorrhages (neurological
      events), four of which were documented on neuroimaging studies, occurred during
      the follow-up period, for an overall event rate of 1.6% per patient per year. No
      patient experienced clinically significant neurological deficits due to recurrent
      hemorrhage. CONCLUSIONS: As many as 40% of patients with a spinal CM may harbor a
      similar intracranial lesion, and approximately 40% of patients with coexisting
      spinal and intracranial CMs may have the nonfamilial (sporadic) form of the
      disease. Patients with symptomatic spinal CMs who are treated nonoperatively may
      have a small risk of clinically significant recurrent hemorrhage. The findings
      will aid in evaluation of surveillance images and in counseling of patients with
      spinal CMs, irrespective of family history.

PMID- 16572650
TI  - Correlation between the efferent venous drainage of the tumor and peritumoral
      edema in intracranial meningiomas: superselective angiographic analysis of 25
      cases.
AB  - OBJECT: The extent of peritumoral brain edema (PTBE) associated with meningiomas
      can be highly variable. The authors studied the correlation between the
      development of efferent venous drainage from the tumor and the degree of PTBE
      that occurs in intracranial meningiomas. METHODS: Twenty-five patients with 27
      intracranial supratentorial meningiomas were investigated to identify the
      correlation between the efferent venous drainage system of the tumor and
      peritumoral edema. The overall mean age of the patients was 54 years. Seventeen
      patients (68%) were female and eight (32%) were male. All patients underwent
      magnetic resonance imaging and digital subtraction angiography. In each
      meningioma, superselective angiography of the dominant feeding artery was
      performed, including the late venous phase to evaluate the development of the
      tumor's draining vein. An edema index (EI) was introduced to serve as an
      objective means by which to judge the extent of PTBE. Eleven meningiomas (41%),
      in which the mean EI was 0.14 +/- 0.10, clearly showed dominant draining veins
      originating from the tumor itself. In the other 16 meningiomas (59%),
      superselective angiography demonstrated no efferent venous drainage from the
      tumor, which could account for this group's mean EI value of 1.49 +/- 1.05 (p <
      0.001). CONCLUSIONS: The current results suggest that hypoplasia of the efferent
      draining vein from the meningioma itself contributes to PTBE formation. The
      development of an efferent venous system mitigates against the formation of PTBE.
      Intratumoral venous congestion can be considered the main cause of PTBE in
      meningiomas.

PMID- 16572651
TI  - Von Hippel-Lindau disease germline mutations in Mexican patients with cerebellar
      hemangioblastoma.
AB  - OBJECT: Central nervous system (CNS) hemangioblastomas are benign vascular tumors
      arising either sporadically or as a manifestation of von Hippel-Lindau (VHL)
      disease, a hereditary cancer syndrome. The authors studied a series of patients
      with CNS hemangioblastomas and their families to identify germline mutations in
      the VHL tumor suppressor gene and to establish a predictive testing and screening
      protocol. METHODS: Patients admitted between 2002 and 2004 to the Instituto
      Nacional de Neurologia y Neurocirugia for hemangioblastoma were prospectively
      enrolled, together with their at-risk family members. The authors performed the
      molecular analysis of the VHL gene by using polymerase chain reaction and direct
      genetic sequencing. All asymptomatic mutation carriers underwent genetic
      counseling and tumor surveillance. Ninety-eight individuals were tested for VHL
      mutations--23 symptomatic and 75 asymptomatic individuals belonging to 16
      families. Seven of the families had definite clinical criteria of VHL disease,
      five had sporadic hemangioblastoma, and four had CNS hemangioblastoma combined
      with minor visceral signs. Molecular genetic testing identified five germline
      mutations in six of the definite VHL families (sensitivity 85%), but none in the
      possible VHL and sporadic hemangioblastoma cases; four of these mutations had
      been previously described and one is a novel mutation present in two unrelated
      families. After patients carrying the mutation were identified, they underwent
      clinical screening and asymptomatic VHL-related lesions were identified in 43%.
      CONCLUSIONS: Genetic testing for mutations in the VHL gene is crucial in patients
      with CNS hemangioblastoma. The prompt identification of patients carrying the
      genetic mutation allows for a multidisciplinary screening protocol to decrease
      morbidity and mortality rates in these patients, while avoiding costly and
      invasive procedures for noncarriers.

PMID- 16572652
TI  - Comparison of multislice computerized tomography angiography and digital
      subtraction angiography in the postoperative evaluation of patients with clipped
      aneurysms.
AB  - OBJECT: In this study the accuracy of multislice computerized tomography (MSCT)
      angiography in the postoperative examination of clip-occluded intracranial
      aneurysms was compared with that of intraarterial digital subtraction (DS)
      angiography METHODS: Forty-nine consecutive patients with 60 clipped aneurysms
      (41 of which had ruptured) were studied with the aid of postoperative MSCT and DS
      angiography. Both types of radiological studies were reviewed independently by
      two observers to assess the quality of the images, the artifacts left by the
      clips, the completeness of aneurysm occlusion, the patency of the parent vessel,
      and the duration and cost of the examination. The quality of MSCT angiography was
      good in 42 patients (86%). Poor-quality MSCT angiograms (14%) were a result of
      the late acquisition of images in three patients and the presence of clip or
      motion artifacts in four. Occlusion of the aneurysm on good-quality MSCT
      angiograms was confirmed in all but two patients in whom a small (2-mm) remnant
      was confirmed on DS angiograms. In one patient, occlusion of a parent vessel was
      seen on DS angiograms but missed on MSCT angiograms. The sensitivity and
      specificity for detecting neck remnants on MSCT angiography were both 100%, and
      the sensitivity and specificity for evaluating vessel patency were 80 and 100%,
      respectively (95% confidence interval 29.2-100%). Interobserver agreements were
      0.765 and 0.86, respectively. The mean duration of the examination was 13 minutes
      for MSCT angiography and 75 minutes for DS angiography (p < 0.05). Multislice CT
      angiography was highly cost effective (p < 0.01). CONCLUSIONS: Current-generation
      MSCT angiography is an accurate noninvasive tool used for assessment of clipped
      aneurysms in the anterior circulation. Its high sensitivity and low cost warrant
      its use for postoperative routine control examinations following clip placement
      on an aneurysm. Digital subtraction angiography must be performed if the
      interpretation of MSCT angiograms is doubtful or if the aneurysm is located in
      the posterior circulation.

PMID- 16572653
TI  - Dynamic perfusion computerized tomography in cerebral vasospasm following
      aneurysmal subarachnoid hemorrhage: a comparison with technetium-99m-labeled
      ethyl cysteinate dimer-single-photon emission computerized tomography.
AB  - OBJECT: The aim of this study was to correlate cerebral blood flow (CBF) and mean
      transient time (MTT) measured on dynamic perfusion computerized tomography (CT)
      with CBF using (99m)Tc ethyl cysteinate dimer-single-photon emission computerized
      tomography (SPECT) in patients with cerebral vasospasm following aneurysmal
      subarachnoid hemorrhage (SAH). METHODS: Thirty-five patients with vasospasm
      following aneurysmal SAH (12 men and 23 women with a mean age of 49.3 +/- 10.1
      years) underwent imaging studies; thus, 35 perfusion CT scans and 35 SPECT images
      were available for comparison. The CBF and MTT values in 12 different brain
      regions were defined relative to the interhemispheric occipital cortex values
      using perfusion CT scans and were compared with qualitative relative (rel)CBF
      estimated on SPECT images. In brain regions with normal, mild (relCBF 71-85%),
      moderate (relCBF 50-70%), and severe (relCBF < 50%) hypoperfusion on SPECT, the
      mean relCBF values measured on perfusion CT were 1.01 +/- 0.08, 0.82 +/- 0.22,
      0.6 +/- 0.15, and 0.32 +/- 0.08, respectively (p < 0.0001); the mean relMTT
      values were 1.04 +/- 0.14, 1.4 +/- 0.31, 2.16 +/- 0.46, and 3.3 +/- 0.54,
      respectively (p < 0.0001). All but one brain region (30 regions) with severe
      hypoperfusion on SPECT images demonstrated relCBF values less than 0.6 and relMTT
      values greater than 2.5 on perfusion CT scans. CONCLUSIONS: Relative CBF and MTT
      values on perfusion CT showed a high concordance rate with estimated relCBF on
      SPECT in patients with vasospasm following aneurysmal SAH. Given its logistical
      advantages, perfusion CT may be a valuable method of assessing perfusion
      abnormality in the acute setting of vasospasm and in patients with an unstable
      condition following aneurysmal SAH.

PMID- 16572654
TI  - Motor neuronal and glial apoptosis in the adult facial nucleus after intracranial
      nerve transection.
AB  - OBJECT: Intracranial lesions affecting the facial nerve are usually associated
      with significant morbidity and poor functional restitution, despite the fact that
      a peripheral nerve injury normally recovers well. Mechanistic explanations are
      needed to direct future therapies. Although neonatal motor neurons are known to
      die as a result of apoptosis after axotomy, this cell death mechanism has not
      been explicitly demonstrated after peripheral cranial nerve transection in adult
      mammals. METHODS: The authors induced substantial retrograde neuronal death in
      the adult rodent by transecting the facial nerve during its intracranial course.
      Neuronal apoptosis was demonstrated as shrunken facial motor neurons,
      retrogradely labeled with fluorogold and with nuclei positively labeled by
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labeling (TUNEL). Glial apoptosis was demonstrated by double labeling with
      respect to cell type. On postinjury Days 7 and 14, the intracranial axotomy led
      to neuronal apoptosis, corresponding to a neuronal loss that was observed
      quantitatively in cresyl violet-stained tissue sections obtained using a
      stereological method. In contrast, no neuronal apoptosis was observed after
      creating a distal lesion of the facial nerve, which causes less neuronal loss. In
      addition, glial apoptosis was seen in the facial nucleus after both distal and
      proximal axotomy. Whereas the proximal intracranial axotomy led to TUNEL-positive
      nuclei in cells showing markers for oligodendrocytes and microglia, only the
      latter glial cell population was double labeled with TUNEL-positive nuclei after
      distal lesioning. CONCLUSIONS: These findings may ultimately lead to new
      therapeutic strategies in patients suffering from facial nerve palsy due to an
      intracranial lesion.

PMID- 16572655
TI  - Comparison between the microscope and endoscope in the direct endonasal extended
      transsphenoidal approach: anatomical study.
AB  - OBJECT: The authors compare the views afforded by the operating microscope and
      the endoscope in the direct endonasal extended transsphenoidal approach to the
      sellar, suprasellar, and parasellar regions. METHODS: Five formalin-fixed,
      silicone-injected adult cadaveric heads were studied. A direct endonasal
      transsphenoidal approach was performed via the right nostril, pushing aside the
      nasal septum. The approach was performed with the microscope first, then with the
      endoscope. For each step (sellar, suprasellar, and clival), the exposure afforded
      by direct microscopic view was measured and then compared with that obtained
      using the endoscope. The direct endonasal approach provides a slightly off
      midline view. Although the microscope provides an adequate view of the midline
      structures and part of the contralateral parasellar areas, the addition of the
      endoscope allows for a more panoramic view and permits widening of the approach
      in all directions. CONCLUSIONS: An adequate exposure of the sellar, suprasellar,
      and infrasellar/upper clival regions can be achieved via a simple, direct
      endonasal approach. From a direct endonasal route, there is a preferential
      visualization of the structures contralateral to the approach. The endoscope
      affords a more panoramic view that extends the area covered by the operating
      microscope.

PMID- 16572656
TI  - Medical application of an infrared free-electron laser: selective removal of
      cholesterol ester in carotid artery atheromatous plaques.
AB  - OBJECT: . The purpose of this study was to determine the effectiveness of
      infrared free-electron laser (FEL) irradiation of cholesterol esters in human
      carotid artery (CA) atheromas. METHODS: The degradation of cholesterol ester was
      estimated from changes in the infrared absorption spectra acquired using
      microscopic transmission Fourier transform infrared spectroscopy. An FEL emitting
      radiation at 5.75-microm wavelengths and a power density of 15.9 W/cm2 was used
      to treat intimal slices of extirpated human arterial atherosclerotic plaques.
      Peak signals derived from an ester bond of cholesterol ester decreased in height
      as irradiation time increased and disappeared completely after 180 seconds. No
      other change was observed in the infrared absorption spectrum after 180 seconds
      of irradiation, and no histological damage was noted. CONCLUSIONS: The authors
      concluded that FEL irradiation can remove cholesterol ester selectively from
      human atheromatous CA plaques. This novel technique differs from previous
      approaches involving conventional lasers.

PMID- 16572657
TI  - The marginal sinus.
AB  - OBJECT: Descriptions of the marginal venous sinus are lacking in the extant
      medical literature. The aim of this study was to characterize the anatomy of this
      intracranial venous sinus. METHODS: The authors examined the marginal sinuses in
      15 adult cadavers following the injection of latex into the intracranial venous
      system. The maximal vertical height of the sinuses, which ranged from 7 to 15 mm
      (mean 10 mm), was located at the lateral aspect of the foramen magnum at or near
      the region at which the spinal accessory nerve crossed en route to the jugular
      foramen. In all specimens the sinus tapered as it traveled both anteriorly and
      posteriorly. Ninety-three percent of the specimens demonstrated significant
      drainage into the veins of the hypoglossal canal. The hypoglossal nerve rootlets
      pierced the sinus and its tributaries in 11 (73%) of 15 specimens. The marginal
      sinus communicated with the basilar venous plexus in 12 (80%) of 15 specimens and
      with the occipital sinus in all specimens (100%). There was venous communication
      with the sigmoid sinus in all specimens. The vertebral artery coursed through the
      marginal sinus as it pierced the posterior atlantooccipital membrane in all left
      sides and in 87% of the right sides. CONCLUSIONS: These quantitative data will be
      useful to the neurosurgeon who operates in the region of the marginal sinus.

PMID- 16572658
TI  - Malacoplakia of the cranium and cerebrum in a human immunodeficiency virus
      infected man. Case report.
AB  - Malacoplakia is a rare chronic inflammatory disease associated with infection and
      immunosuppression, and very few occurrences have been reported in the cerebrum.
      The authors describe the case of a 41-year-old man with advanced human
      immunodeficiency virus (HIV) infection who presented with a very aggressive
      malacoplakia lesion that had extended through the scalp, temporalis muscle, skull
      bone, and deep through the dura mater into the superior sagittal sinus and
      adjacent brain. Pathological examination revealed sheets of histiocytes invading
      these structures, and macrophages containing numerous round bodies known as
      Michaelis-Guttmann bodies, pathognomic for malacoplakia. Because of the rarity of
      this phenomenon, appropriate treatment and management of malacoplakia are
      speculative. A complete resection of the lesion, antibiotic therapy, and
      treatment of his underlying HIV infection had a salutary effect, with the patient
      faring well more than 9 months postoperatively.

PMID- 16572659
TI  - Episodic nocturnal wandering in a patient with epilepsy due to a right
      temporoinsular low-grade glioma: relief following resection. Case report.
AB  - Although controversial, episodic nocturnal wandering (ENW) is thought to be a
      rare and atypical form of nocturnal epilepsy, originating in the frontal lobe and
      responsive to antiepileptic drugs (AEDs). The authors report the case of a
      patient harboring a right temporoinsular low-grade glioma, who presented with a 3
      year history of agitated somnambulent episodes resistant to AEDs. Interestingly,
      the ENW totally resolved after tumor resection and the patient reported no
      recurrence during a follow-up period of 4.5 years. To the authors' knowledge,
      this is the first report of ENW due to a glioma; the findings support the theory
      that ENW may represent an unusual type of lesional epilepsy that is surgically
      correctable. Moreover, a temporoinsular origin of ENW can now be considered.

PMID- 16572660
TI  - Primary myxoma of the parafalcine meninges. Case report.
AB  - The authors report on an unusual case of a primary intracranial myxoma in a 39
      year-old woman. The patient presented with headache and generalized seizure.
      Magnetic resonance imaging revealed a large right frontal tumor resembling a
      parasagittal meningioma. A gross-total resection was performed, and histological
      review confirmed the lesion as a myxoma. Results of additional workup revealed
      the absence of a primary myxoma elsewhere. This case represents the third
      published report of a primary intracranial myxoma and the second report of a
      supratentorial myxoma.

PMID- 16572661
TI  - Coexisting intracranial meningeal melanocytoma, dermoid tumor, and Dandy-Walker
      cyst in a patient with neurocutaneous melanosis. Case report.
AB  - Neurocutaneous melanosis (NCM) associated with Dandy-Walker malformation is a
      very rare congenital neurodysplasia with the same origin. Primary intracranial
      melanocytic and dermoid tumors are also benign congenital lesions that usually
      arise from the leptomeninges and are formed by the inclusion of cutaneous
      ectoderm at the time of neural tube closure. The authors describe a patient with
      coexisting intracranial meningeal melanocytoma, NCM with Dandy-Walker
      malformation, and intraventricular dermoid tumor.

PMID- 16572662
TI  - Unilateral Holmes tremor, clearly responsive to cerebrospinal fluid release, in a
      patient with an ischemic midbrain lesion and associated chronic hydrocephalic
      ventricle enlargement. Case report.
AB  - The authors describe a 58-year-old man with sudden onset of a unilateral tremor
      caused by a midbrain lesion that affected the substantia nigra and the
      cerebellothalamic pathway. There were also clinical and neuroimaging signs of a
      communicating chronic hydrocephalus. The patient was severely handicapped by this
      tremor, which was a typical Holmes tremor with rest, posture, and intention
      components. Parkinson disease or multiple-system atrophy as causes for the tremor
      could be ruled out by DaTSCAN and 123I iodobenzamide and single-photon emission
      computerized tomography (SPECT), respectively. The tremor was completely
      supressed by temporary and permanent cerebrospinal fluid release after
      ventriculoperitoneal shunt placement, without any additional medication, for a
      period of 6 months. Afterward, the tremor returned, and the patient had to be
      treated by a stereotactic electrode implantation in the contralateral ventralis
      intermedius nucleus, which led to complete tremor suppression during the 1.5-year
      follow-up period. In this case report, the authors present the clinical
      description and the electrophysiological, SPECT, and magnetic resonance imaging
      data of a rare combination of symptoms and their surgical treatment.

PMID- 16572663
TI  - Iatrogenic cerebellar implantation of a vestibular schwannoma. Case report.
AB  - Metastatic seeding or iatrogenic implantation of numerous types of primary
      central nervous system tumors, typically along cerebrospinal fluid pathways, is a
      frequently described albeit rare phenomenon and has never been reported in
      association with vestibular schwannoma (VS). The authors present a case of
      inadvertent surgical implantation of VS into the cerebellar hemisphere during
      resection of a recurrent VS in the cerebellopontine angle and internal auditory
      canal. A 42-year-old man presented with a 2.5-cm right VS that was removed
      without complication via a retrosigmoid approach. Routine imaging performed 5
      years later revealed a 1.5-cm recurrence of the VS that was subsequently removed
      by reopening the retrosigmoid craniotomy. Five years later--10 years after
      initial presentation--follow-up imaging revealed a 1-cm recurrence of the VS and
      a separate 2.2-cm tumor in the inferior cerebellar parenchyma with surrounding
      edema. Both tumors were removed without complication by reopening the previous
      retrosigmoid craniotomy. Histological evaluation of these tumors revealed
      features typical of VS and similar to those of the tissue obtained from the two
      prior resections. Given the similarities among these tumors in pathological
      appearance and mitotic index, the presence of the intraparenchymal cerebellar
      schwannoma was probably due to intraoperative iatrogenic implantation.

PMID- 16572664
TI  - End-to-side intrapetrous hypoglossal-facialanastomosis for reanimation of the
      face. Technical note.
AB  - The aim of this paper was to report on further experience with a new technique
      for reanimation of the facial nerve. This procedure allows a straight end-to-side
      hypoglossal-facial anastomosis without interruption of the 12th cranial nerve or
      the need for graft interposition. It is technically demanding and time consuming
      but offers an effective, reliable, and extraordinarily quick means of
      reinnervating the facial muscles, including the orbicularis oculi muscle, thus
      avoiding the need for a gold weight in the eyelid or a fascial sling.

PMID- 16572665
TI  - [A head issue].

PMID- 16572666
TI  - [Not using two different measurements].

PMID- 16572667
TI  - [Hygiene in nursing--9: Infusions and injections: preventing infections and
      needlestick injuries].

PMID- 16572668
TI  - [Hospital infections in nursing homes--3: Increase in multiple resistances].

PMID- 16572669
TI  - [Post-discharge nursing documentation of on the use of disability aids:
      preventing mismanagement].

PMID- 16572670
TI  - [Neurobiological principles of consciousness: understanding oneself and others].

PMID- 16572671
TI  - [Palliative nursing of patients with dementia: a good relationship determines the
      quality of nursing care].

PMID- 16572672
TI  - [Basal stimulation of persons in a vegetative state--a case report: back into a
      more aware life].

PMID- 16572673
TI  - [Successful nursing care of a patient in vegetative state: perceiving the
      qualities of individual nursing care].

PMID- 16572674
TI  - [Self determination of patients with mental handicap: measure of nursing
      quality].

PMID- 16572675
TI  - [Daily routine in German nursing homes: "neglect was universal" (interview by
      Brigit Ruck)].

PMID- 16572676
TI  - [Nursing in Europe--Luxemborg: developing and utilizing new nursing fields].

PMID- 16572677
TI  - [From case to case: it happened in the evening].

PMID- 16572678
TI  - [Abdominal massage as intervention for patients with paraplegia caused by spinal
      cord injury--a pilot study].
AB  - Patients with paraplegia caused by spinal cord injuries have to deal with the
      loss of the central nervous regulation of the bowel functions. The management of
      defaecation can take a lot of their daily time. To support the colon motility,
      different methods of abdominal massage are used in nursing practice. But a review
      of current international literature reveals, that there is still a lack of
      evidence for the effect of abdominal massage on defaecation. In order to prove
      this effect, a pilot study was conducted using a quasi-experimental design with
      time series and including seven patients with paraplegia caused by spinal cord
      injury. Data were collected over three weeks: one week before intervention,
      during the intervention week and one week after intervention. In the intervention
      week, the patients received a specific abdominal massage each morning before
      breakfast. Following outcome-criteria have been considered: frequency and
      duration of defaecation, amount and consistency of faeces as well as subjective
      perception of the massage and its effects. RESULTS: Some distinctive changes in
      the frequency and duration of defaecation could be registered over time. Most
      patients regarded the massage as a comfortable intervention that may have
      positive effects of the defaecation. Due to the pilot character of the study
      further research is necessary in order to validate these effects.

PMID- 16572679
TI  - [Delirium--etiologies, symptoms, risk factors, assessment and interventions].
AB  - Delirium (acute confusion) in elderly people is common and can present as an
      emergency. The magnitude of the problem is often overlooked or underestimated in
      clinical practice. Many healthcare providers find that caring for delirious
      patients is very stressful. However, with systematic screening, preventive
      interventions, and immediate treatment, the incidence, duration and severity of
      delirium can be appropriately managed, which in turn can minimise complications
      and long-term damage. Successful intervention programs that are based on targeted
      and interdisciplinary multicomponent strategies have been developed. Nurses can
      play a pivotal role in these types of delirium management programs. The stress of
      caring for delirious patients can also be reduced through the implementation of
      such programs.

PMID- 16572680
TI  - Surface-relief fiber Bragg gratings for sensing applications.
AB  - We present a new type of fiber Bragg grating (FBG) in which we etch the grating
      into the flat surface of a D-shaped optical fiber. Instead of being written in
      the core of the fiber, as are standard FBGs, these surface-relief FBGs are placed
      in the cladding above the core. These gratings are a viable alternative to
      standard FBGs for sensing applications. We describe the fabrication process for
      etching Bragg gratings into the surface of D-fibers and demonstrate their
      performance as temperature sensors.

PMID- 16572681
TI  - Near-normal-incidence extreme-ultraviolet efficiency of a flat crystalline
      anisotropically etched blazed grating.
AB  - We have measured the extreme-ultraviolet (EUV) efficiency at an angle of
      incidence of 10 degrees of a flat crystalline anisotropically etched blazed
      grating. The measured efficiencies are high for uncoated gratings and agree well
      with a calculated model derived from a reasonable estimate of the groove profile.
      The highest groove efficiencies derived from the measurements are 48.8% at 19.07
      nm and 64.1% at 16.53 nm for the -2 and -3 orders, respectively, which are
      comparable to the best values obtained yet from a holographic ion-etched blazed
      grating. This presents opportunities to instrument designs for high-resolution
      EUV spectroscopy in astrophysics where high efficiency in high orders is
      desirable.

PMID- 16572682
TI  - Efficiency of a grazing-incidence off-plane grating in the soft-x-ray region.
AB  - Efficiency measurements of a grazing-incidence diffraction grating in the off
      plane mount were performed using polarized synchrotron radiation. The grating had
      5000 grooves/mm, an effective blaze angle of 14 degrees, and was gold coated. The
      efficiencies in the two polarization orientations (TM and TE) were measured in
      the 1.5-5.0 nm wavelength range and were compared with the efficiencies
      calculated using the PCGrate-SX code. The TM and TE efficiencies differ, offering
      the possibility of performing unique science studies of astrophysical, solar, and
      laboratory sources by exploiting the polarization sensitivity of the off-plane
      grating.

PMID- 16572683
TI  - Polarimetric characterization of liquid-crystal-on-silicon panels.
AB  - Mueller matrix imaging polarimetry of liquid-crystal-on-silicon (LCoS) panels
      provides detailed information useful for the diagnosis of LCoS problems and to
      understand the interaction of LCoS panels with other projector components. Data
      reduction methods are presented for the analysis of LCoS Mueller matrix images
      yielding contrast ratio, efficiency, spatial uniformity, and the calculation of
      optimum trim retarders. The effects of nonideal retardance, retardance
      orientation, and depolarization on LCoS system performance are described. The
      white-state and dark-state Mueller matrix images of an example LCoS panel are
      analyzed in terms of LCoS performance metrics typical for red-green-blue
      wavelengths of 470, 550, and 640 nm. Variations of retardance, retardance
      orientation, and depolarization are shown to have different effects on contrast
      ratio, efficiency, and brightness. Thus Mueller matrix images can diagnose LCoS
      problems in a way different from radiometric testing. The calculation of optimum
      trim retarders in the presence of spatial variations is discussed. The
      relationship of the LCoS retardance in single-pass (from front to back) to the
      double-pass retardance (from entrance to exit) is established and used to clarify
      coordinate system issues related to Mueller matrices for reflection devices.

PMID- 16572684
TI  - Integral three-dimensional television using a 2000-scanning-line video system.
AB  - We have developed an integral three-dimensional (3-D) television that uses a 2000
      scanning-line video system that can shoot and display 3-D color moving images in
      real time. We had previously developed an integral 3-D television that used a
      high-definition television system. The new system uses -6 times as many elemental
      images [160 (horizontal) x 118 (vertical) elemental images] arranged at -1.5
      times the density to improve further the picture quality of the reconstructed
      image. Through comparison an image near the lens array can be reconstructed at 
      1.9 times the spatial frequency, and the viewing angle is -1.5 times as wide.

PMID- 16572685
TI  - Imaging with a rectangular phase grating applied to displacement metrology.
AB  - We achieved displacement metrology with a high-amplitude signal by using a
      rectangular phase grating as the pupil in a grating imaging system. The imaging
      phenomenon with a pupil transmission grating that has a bilevel profile with a
      50% duty ratio is discussed on the basis of the optical transfer function. By
      optimizing the imaging condition, we obtained high-contrast images with high
      light power under a magnified or demagnified imaging system. The amplitude of the
      signal in the displacement measurement was four times higher than that of the
      conventional grating imaging system with amplitude gratings.

PMID- 16572686
TI  - Optical properties of fluids for 248 and 193 nm immersion photolithography.
AB  - We present measured values of the refractive index, thermo-optic coefficient, and
      absorption coefficient of a number of common organic solvents and aqueous
      inorganic solutions that may have application in immersion photolithography at
      248 or 193 nm wavelengths. The measurements were performed with a laser-based
      Hilger-Chance refractometer system whose design and operation are described. The
      optical properties of the sample fluids are compared with those of water, the
      currently favored immersion medium, and we discuss the potential for finding
      higher-index fluids that will be suitable for this application.

PMID- 16572687
TI  - Angle amplification for nanoradian measurements.
AB  - A method to amplify the rotation angle of a mirror, based on multiple reflections
      between two quasi-parallel mirrors, is presented. The method allows rotations of
      fractions of nanoradians to be measured with a simple setup. The working
      principle, the experimental setup, and the results are presented.

PMID- 16572688
TI  - Direct index of refraction measurements at extreme-ultraviolet and soft-x-ray
      wavelengths.
AB  - Coherent radiation from undulator beamlines has been used to directly measure the
      real and imaginary parts of the index of refraction of several materials at both
      extreme-ultraviolet and soft-x-ray wavelengths. Using the XOR interferometer, we
      measure the refractive indices of silicon and ruthenium, essential materials for
      extreme-ultraviolet lithography. Both materials are tested at wavelength (13.4
      nm) and across silicon's L2 (99.8 eV) and L3 (99.2 eV) absorption edges. We
      further extend this direct phase measurement method into the soft-x-ray region,
      where measurements of chromium and vanadium are performed around their L3
      absorption edges at 574.1 and 512.1 eV, respectively. These are the first direct
      measurements, to our knowledge, of the real part of the index of refraction made
      in the soft-x-ray region.

PMID- 16572689
TI  - Microelectromechanical system pressure sensor integrated onto optical fiber by
      anodic bonding.
AB  - Optical microelectromechanical system pressure sensors based on the principle of
      Fabry-Perot interferometry have been developed and fabricated using the technique
      of silicon-to-silicon anodic bonding. The pressure sensor is then integrated onto
      an optical fiber by a novel technique of anodic bonding without use of any
      adhesives. In this anodic bonding technique we use ultrathin silicon of thickness
      10 microm to bond the optical fiber to the sensor head. The ultrathin silicon
      plays the role of a stress-reducing layer, which helps the bonding of an optical
      fiber to silicon having conventional wafer thickness. The pressure-sensing
      membrane is formed by 8 microm thick ultrathin silicon acting as a membrane, thus
      eliminating the need for bulk silicon etching. The pressure sensor integrated
      onto an optical fiber is tested for static response, and experimental results
      indicate degradation in the fringe visibility of the Fabry-Perot interferometer.
      This effect was mainly due to divergent light rays from the fiber degrading the
      fringe visibility. This effect is demonstrated in brief by an analytical model.

PMID- 16572690
TI  - Systematic modeling study of channel waveguide fabrication by thermal silver ion
      exchange.
AB  - A systematic study of thermal silver ion exchange used for the fabrication of
      optical channel waveguides is reported in a single-alkali glass. The diffusion
      equilibrium and diffusion dynamics are experimentally studied, and the
      concentration-dependent diffusion coefficients are determined. The relationship
      between the fabrication conditions, i.e., time, temperature, and melt
      concentration, and the induced waveguide refractive index profile is established.
      It is demonstrated that the diffusion equation can be solved, without use of any
      free parameters, to predict the refractive index profiles of both planar and
      channel waveguides. A 1.6 cm diameter integrated optic ring resonator, with a
      propagation loss of 0.1 dB/cm, is fabricated in a glass by thermal silver ion
      exchange. The induced refractive index profile is related to the optical
      characteristics of the functional device.

PMID- 16572691
TI  - Multiple-scattering suppression in dynamic light scattering based on a digital
      camera detection scheme.
AB  - We introduce a charge-coupled device (CCD) camera-based detection scheme in
      dynamic light scattering that provides information on the single-scattered
      autocorrelation function even for fairly turbid samples. It is based on the
      single focused laser beam geometry combined with the selective cross-correlation
      analysis of the scattered light intensity. Using a CCD camera as a multispeckle
      detector, we show how spatial correlations in the intensity pattern can be linked
      to single- and multiple-scattering processes. Multiple-scattering suppression is
      then achieved by an efficient cross-correlation algorithm working in real time
      with a temporal resolution down to 0.02 s. Our approach allows access to the
      extensive range of systems that show low-order scattering by selective detection
      of the singly scattered light. Model experiments on slowly relaxing suspensions
      of titanium dioxide in glycerol were carried out to establish the validity range
      of our approach. Successful application of the method is demonstrated up to a
      scattering coefficient of more than micro(S) = 5 cm(-1) for the sample size of L
      = 1 cm.

PMID- 16572692
TI  - SiC/Tb and Si/Tb multilayer coatings for extreme ultraviolet solar imaging.
AB  - Narrowband SiC/Tb and Si/Tb multilayers are fabricated with as much as a 23%
      normal-incidence reflectance near a 60 nm wavelength and spectral bandpass (FWHM)
      values of 9.4 and 6.5 nm, respectively. The structural properties of the films
      are investigated using extreme ultraviolet and x-ray reflectometry and
      transmission electron microscopy. Thermal stability is investigated in films
      annealed to as high as 300 degrees C. Because of their superior thermal
      stability, relatively high reflectance, and narrower spectral bandpass, Si/Tb
      multilayers are identified as optimal candidates for solar physics imaging
      applications, where the peak response can be tuned to important emission lines
      such as O v near 63.0 nm and Mg x near 61.0 nm. We describe our experimental
      procedures and results, discuss the implications of our findings, and outline
      prospects for improved performance.

PMID- 16572693
TI  - Multigate single-photon detection and timing discrimination with an InGaAs/lnP
      avalanche photodiode.
AB  - Multigate detection of single photons at 1550 nm is achieved by using capacitor
      balanced InGaAs/InP avalanche photodiodes, with which we experimentally
      demonstrate the efficient discrimination of single-photon timing by counting
      single-photon clicks and the corresponding afterpulses within the multiple gates.
      Results show that the technique of multigate detection is a practical method for
      the single-photon timing information process.

PMID- 16572694
TI  - Form-birefringent space-variant inhomogeneous medium element for shaping point
      spread functions.
AB  - We experimentally characterize the properties of an element that generates a
      doughnutlike point-spread function by converting the linearly polarized incident
      field to radially or azimuthally polarized light utilizing space-variant
      inhomogeneous medium (SVIM) form-birefringent subwavelength structures. To
      fabricate the high-aspect-ratio SVIM structures, we developed a chemically
      assisted ion-beam-etching process that permits control of the fabricated form
      birefringent structure profile to optimize the effect of birefringence and the
      impedance mismatch on the substrate-air interface. Fabricated elements perform
      efficient polarization conversion for incident angles as large as 30 degrees,
      where the extinction ratio is found to be better than 4.5. The intensity
      distribution in the far field shows that our SVIM device generates a doughnut
      point-spread function that may prove useful for various applications.

PMID- 16572695
TI  - Focusing characteristics of a planar solid-immersion mirror.
AB  - The focusing characteristics of a planar waveguide solid-immersion mirror with
      parabolic design have been investigated. The solid-immersion mirror is integrated
      into an optical waveguide, and light focusing is achieved with a parabolic mirror
      parallel to the waveguide plane and waveguide mode confinement normal to the
      waveguide plane. Optical-quality tantala silica planar waveguides can be obtained
      by evaporation. The parabolic sidewall reflects over 50% of the incident
      waveguide mode and generates a diffraction-limited focus. The measured spot size
      for the solid-immersion mirror described here is less than one third of the
      wavelength. Polarization analysis shows that the electric field near the focal
      region has components parallel and normal to the polarization state of the
      incident beam. The planar solid-immersion mirror is essentially free of chromatic
      aberration, and the alignment of the illumination beam is within a fraction of
      degrees.

PMID- 16572696
TI  - Proposal for a multilayer read-only-memory optical disk structure.
AB  - Coherent interlayer cross talk and stray-light intensity of multilayer read-only
      memory (ROM) optical disks are investigated. From results of scalar diffraction
      analyses, we conclude that layer separations above 10 microm are preferred in a
      system using a 0.85 numerical aperture objective lens in terms of signal quality
      and stability in focusing control. Disk structures are optimized to prevent
      signal deterioration resulting from multiple reflections, and appropriate
      detectors are determined to maintain acceptable stray-light intensity. In the
      experiment, quadrilayer and octalayer high-density ROM disks are prepared by
      stacking UV-curable films onto polycarbonate substrates. Data-to-clock jitters of
      < or = 7% demonstrate the feasibility of multilayer disk storage up to 200
      Gbytes.

PMID- 16572697
TI  - Resonant coupling between bulk waves and guided modes in a dielectric slab with a
      thick holographic grating.
AB  - What we believe to be a new type of resonant coupling of an incident bulk wave
      into guided modes of a slab with a thick holographic grating is shown to occur in
      the presence of strong frequency detunings of the Bragg condition. This happens
      through the reflection of the strongly noneigen +1 diffracted order with the slab
      grating boundaries, the resultant reflected waves forming a guided slab mode.
      Rigorous coupled-wave analysis is used for the numerical analysis of the
      predicted resonant effects. Possible applications include enhanced options for
      the design of multiplexing and demultiplexing systems, optical signal-processing
      devices, optical sensors, and measurement techniques.

PMID- 16572698
TI  - Optical trap stiffness in the presence and absence of spherical aberrations.
AB  - Optical traps are commonly constructed with high-numerical-aperture objectives.
      Oil-immersion objectives suffer from spherical aberrations when used for imaging
      in aqueous solutions. The effect of spherical aberrations on trapping strength
      has been modeled by approximation, and only a few experimental results are
      available in the case of micrometer-sized particles. We present an experimental
      study of the dependence of lateral and axial optical-trap stiffness on focusing
      depth for polystyrene and silica beads of 2 microm diameter by using oil- and
      water-immersion objectives. We demonstrate a strong depth dependence of trap
      stiffness with the oil-immersion objective, whereas no depth dependence was
      observed with the water-immersion objective.

PMID- 16572699
TI  - Current-dependent spectral blueshift in a three-dimensional photonic-quantum-ring
      laser.
AB  - The emission spectra of photonic-quantum-ring lasers can be explained by a three
      dimensional Rayleigh-Fabry-Perot cavity resonance model. The proposed model for
      the emission spectral peaks fits well with the observed blueshift of the emission
      spectrum envelope as a function of the view angle. Furthermore, we observe that
      the emission spectra with the high-order mode index showed blueshift behaviors as
      functions of the injection current, whereas those with the low-order mode index
      showed redshift behaviors. These phenomena might result in lowering the effective
      refractive index by the carrier inhomogeneity in the active disk.

PMID- 16572700
TI  - Diode-pumped passively Q-switched Nd:YVO4 green laser with a periodically poled
      KTP and Cr4+:YAG saturable absorber.
AB  - A diode-pumped passively Q-switched Nd:YVO4 green laser with a periodically poled
      KTP and Cr4+:YAG saturable absorber is realized. The dependences of pulse
      repetition rate, pulse energy, pulse width, and peak power on incident pump power
      are measured for the generated green-light pulses. A rate-equation model is
      introduced to theoretically analyze the results obtained in the experiment, in
      which the spatial distribution of the intracavity photon density is taken into
      account. The numerical solutions of the rate equations agree with the
      experimental results.

PMID- 16572701
TI  - Micro-optically assisted high-index waveguide coupling.
AB  - Adapting the concept of solid immersion lenses, we numerically study a micro
      optical scheme for conventional high-index and photonic-crystal waveguide
      coupling by using a combination of different numerical methods such as ray
      tracing, angular-spectrum propagation, finite-difference time-domain simulations,
      and finite-element-method simulations. The numerical findings are discussed by
      means of impedance, group- or energy-velocity, spot-size, and phase-matching
      criteria. When fabrication constraints for high-index immersion lenses made of
      silicon are taken into account, a coupling efficiency of -80% can be reached for
      monomode silicon-on-insulator waveguides with a quadratic cross section of the
      core and rectangular cross sections of moderate aspect ratio. Similar coupling
      efficiencies of -80% can be obtained for silicon-on-insulator photonic-crystal
      waveguides. Tolerances that are due to misalignments and variations of the
      substrate thickness of the silicon lens are discussed.

PMID- 16572702
TI  - Optical detection of honeybees by use of wing-beat modulation of scattered laser
      light for locating explosives and land mines.
AB  - An instrument is demonstrated that can be used for optical detection of honeybees
      in a cluttered environment. The instrument uses a continuous-wave diode laser
      with a center wavelength of 808 nm and an output power of 28 mW as the laser
      transmitter source. Light scattered from moving honeybee wings will produce an
      intensity-modulated signal at a characteristic wing-beat frequency (170-270 Hz)
      that can be used to detect the honeybees against a cluttered background. The
      optical detection of honeybees has application in the biological detection of
      land mines and explosives, as was recently demonstrated.

PMID- 16572703
TI  - Effect of particles on ultraviolet light penetration in natural and engineered
      systems.
AB  - The effect of light scattering on measurement of UV absorbance and penetration of
      germicidal UVC irradiance in a UV reactor were studied. Using a standard
      spectrophotometer, absorbance measurements exhibited significant error when
      particles that scatter light were present but could be corrected by integrating
      sphere spectroscopy. Particles from water treatment plants and wastewater
      effluents exhibited less scattering (20%-30%) compared with particles such as
      clay (50%) and alumina (95%-100%). The distribution of light intensity in a UV
      reactor for a scattering suspension was determined using a spherical chemical
      actinometry method. Highly scattering alumina particles increased the fluence
      rate in the reactor near the UV lamp, whereas clay particles and absorbing
      organic matter reduced the fluence rate. A radiative transfer fluence rate model
      reasonably predicted the fluence rate of absorbing media and highly scattering
      suspensions in the UV reactor.

PMID- 16572704
TI  - Terahertz wave propagation in one-dimensional periodic dielectrics.
AB  - We demonstrate the temporal evolution of terahertz (THz) wave propagation in one
      dimensional periodic dielectrics. Distributed Bragg reflectors and a resonant
      cavity are investigated: The structures involve air gaps interleaved between
      polymer films. Transmitted and reflected broadband THz waves are measured by
      means of THz time-domain spectroscopy. The experimental results agree well with
      transfer matrix calculations.

PMID- 16572705
TI  - Simultaneous B-M-mode scanning method for real-time full-range Fourier domain
      optical coherence tomography.
AB  - High-speed complex full-range Fourier domain optical coherence tomography (FD
      OCT) is demonstrated. In this FD-OCT, the phase modulation of a reference beam (M
      scan) and transversal scanning (B scan) are simultaneously performed. The Fourier
      transform method is applied along the direction of the B scan to reconstruct
      complex spectra, and the complex spectra comprise a full-range OCT image. Because
      of this simultaneous B-M-mode scan, the FD-OCT requires only a single A scan for
      each single transversal position to obtain a full-range FD-OCT image. A simple
      but slow version of the FD-OCT visualizes the cross section of a plastic plate. A
      modified fast version of this FD-OCT investigates a sweat duct in a finger pad in
      vivo and visualizes it with an acquisition time of 27 ms.

PMID- 16572706
TI  - Two-dimensional quantitative photoacoustic image reconstruction of absorption
      distributions in scattering media by use of a simple iterative method.
AB  - Photoacoustic imaging is a noninvasive biomedical imaging modality for
      visualizing the internal structure and function of soft tissues. Conventionally,
      an image proportional to the absorbed optical energy is reconstructed from
      measurements of light-induced acoustic emissions. We describe a simple iterative
      algorithm to recover the distribution of optical absorption coefficients from the
      image of the absorbed optical energy. The algorithm, which incorporates a
      diffusion-based finite-element model of light transport, converges quickly onto
      an accurate estimate of the distribution of absolute absorption coefficients. Two
      dimensional examples with physiologically realistic optical properties are shown.
      The ability to recover optical properties (which directly reflect tissue
      physiology) could enhance photoacoustic imaging techniques, particularly methods
      based on spectroscopic analysis of chromophores.

PMID- 16572707
TI  - Atmospheric pollutants study of particles and metallic elements during high wind
      speed (wind speed >6 m/s) near Taiwan Strait around central Taiwan.
AB  - The purpose of this study was to characterize metallic elements associated with
      atmospheric particulate matter in total suspended particulate (TSP), fine
      particles (particle matter with an aerodynamic diameter of <2.5 microm, PM2.5)
      and coarse particles (particle matter with an aerodynamic diameter of 2.5-10
      microm, PM2.5-10), at high wind speed (wind speed >6 m/s) at Taichung Harbor (TH)
      and Wuci traffic (WT) in central Taiwan from March to December 2004. The
      correlation coefficient (R2) between TSP, coarse, fine particulate concentrations
      versus wind speed at the TH and WT sampling site during high wind speed (>6 m/s)
      are shown in this study. In addition, the correlation coefficients between TSP,
      coarse and fine particles of metallic species versus high wind speed were also
      observed. The results indicated that the correlation coefficient order was TSP>
      coarse>fine for particles at both sampling sites during high wind speed (>6 m/s)
      near central Taiwan. In addition, the concentrations of Fe, Zn, Mn, Cu, Pb, Cr,
      Mg for TSP, coarse and fine particulates were also analysed in this study.

PMID- 16572708
TI  - Subacute administration of tributyltin chloride modulates neurotransmitters and
      their metabolites in discrete brain regions of maternal mice and their F1
      offspring.
AB  - Tributyltin (TBT) compounds have been used as anti-fouling agents and the central
      nervous system is one of its target organs. TBT-induced modulations of
      neurotransmitters in the brains of adult mice have been reported. However, little
      is known about the developmental neurotoxicity of TBT. In this study, we
      evaluated the effects of TBT on neurotransmitters and their metabolites in
      discrete brain regions of female ICR mice and their offspring. Pregnant ICR mice
      were exposed to TBT chloride at concentrations of 0, 15 or 50 ppm in water or 125
      ppm in food. Male offspring were sacrificed at one, two and three weeks after
      birth. The concentrations of norepinephrine, dopamine (DA), dihydoxyphenylacetic
      acid, homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid
      (5-HIAA) were determined in different brain regions by HPLC. All offspring from
      the 125 ppm group died immediately after birth. A significant decrease in the
      body weight of the TBT-treated F1 groups compared to the control group was
      observed in the first week. Significant increases compared to the controls were
      observed for the DA concentration in the striatum of the 50 ppm F1 group, and for
      the HVA concentration in the cerebrum and the 5-HT concentration in the medulla
      oblongata of the 15 and 50 ppm F1 groups in the third week. At three weeks of
      age, the neurotransmitters and their metabolites may be useful indexes for
      developmental neurotoxicity. For the dams, a significant decrease in the 5-HT
      concentration was observed in the cerebellum, medulla, midbrain and striatum of
      the 125 ppm group compared to the control group. A significant decrease in the 5
      HIAA concentration was also observed in the cerebellum, midbrain and striatum of
      the dams in the 125 ppm group compared to the control. TBT may induce a decrease
      in the synthesis of 5-HT in the dams. The discrepancy between dams and offspring
      may be due to several factors such as age, dose, route, sex and pregnancy.

PMID- 16572709
TI  - Characteristic study of ionic species in nano, ultrafine, fine and coarse
      particle size mode at a traffic sampling site.
AB  - A micro-orifice uniform deposit impactor (MOUDI) and a nano-MOUDI were used to
      measure the atmospheric coarse (PM2.5-10), fine (PM2.5), ultrafine (PM0.056-1)
      and nano (<0.056 microm) particle concentrations at a traffic sampling site in
      central Taiwan during the winter period from November 2004 to January 2005.
      Meanwhile, concentrations of major ionic species (Cl-, NO3-, SO(2-)4, NH4+, Na+,
      K+, Ca2+ and Mg2+) were also extracted from various particle size modes (nano,
      ultrafine, fine and coarse) and analysed by ion chromatography (DIONEX-100). The
      mass size distribution of ambient suspended particles exhibited two modes. The
      size ranges of the particles at these two particle size modes were between 1.0
      and 1.8 microm and 3.2 and 5.6 microm, respectively. The average mass media
      aerodynamic diameter (MMAD) of suspended particles was 0.99 microm in this study.
      In addition, statistical methods, such as correlation coefficient and principal
      component analysis, were also used to identify the possible pollutant source for
      various particles size modes (nano, ultrafine, fine and coarse) during the winter
      months at a traffic sampling site in central Taiwan.

PMID- 16572710
TI  - Possible peripheral markers for chronic aluminium toxicity in Wistar rats.
AB  - This investigation gives detailed analysis of peripheral marker enzymes as well
      as neurobehavioral tests following chronic aluminium (Al) exposure (10 mg/kg b.w.
      for 12 weeks intragastrically). We observed a significant decrease in the levels
      of serum cholinesterase after toxicity. The enzymatic activity of cytochrome
      oxidase (CO), the terminal enzyme of the electron transport chain, was
      significantly diminished and that of glucose-6-phosphate dehydrogenase (G-6-PD)
      was significantly enhanced. Neuromuscular co-ordination was assessed using motor
      and memory function tests. Deficits were observed suggesting a probable model for
      chronic Al neurotoxicity.

PMID- 16572711
TI  - Effects of Ginkgo biloba on plasma oxidant injury induced by bleomycin in rats.
AB  - Bleomycin is an anti-neoplastic agent and its clinical usage is limited by its
      toxicity, which is mostly induced by oxygen radicals. The aim of this study was
      to investigate the effect of Ginkgo biloba on plasma indices of oxidants induced
      by bleomycin in rats. Male Sprague-Dawley rats were divided into five groups:
      none medicated or 0.9% NaCl injected or only Ginkgo biloba (orally, 100 mg/kg per
      day for 14 days) or only a single dose of bleomycin (intratracheal, 2.5 U/kg) or
      Gingko biloba and bleomycin-treated groups. After 14 days, blood was taken before
      the rats were sacrificed. The plasma was removed and stored at -85 degrees C
      until the study day. Plasma superoxide dismutase (SOD), glutathione peroxidase
      (GSH-Px) and xanthine oxidase (XO) enzyme activities with malondialdehyde and
      nitric oxide (NO) levels were studied. The levels of malondialdehyde and NO with
      activity of XO were higher in plasma of bleomycin group than the other groups (P
      <0.05). The activities of SOD and GSH-Px were increased in the bleomycin plus
      Gingko biloba group in comparison with the bleomycin group (P <0.05). There was a
      positive correlation between malondialdehyde and NO levels in the bleomycin group
      (r =0.859, P <0.05). There were positive correlations between SOD and GSH-Px
      activities (r =0.760, P <0.05) and between XO activity and malondialdehyde level
      (r =0.822, P <0.05) in the bleomycin plus Gingko biloba group. In conclusion, it
      was thought that bleomycin induced oxidative stress can be prevented by Gingko
      biloba treatment via high anti-oxidant enzyme activity together with decreased
      radical production from XO.

PMID- 16572712
TI  - A survey and measurement of residues of lindane (organochlorine pesticides) in
      four species of the most consumed fish in the Caspian Sea (Iran).
AB  - In this study, samples of four species of the most consumed fish (sefid, koli,
      kilca and kafal fish) were analysed for concentrations of lindane (organochlorine
      pesticides). Fish were caught using electric fishing at four sites (Chalous and
      Babolsar cities, Khazar Abad and Miankaleh regions) in the Mazandaran provinces
      of Iran. Quantitative determination of the lindane was performed by gas
      chromatography electron-capture detection (GC-ECD). Samples contained detectable
      concentrations of lindane, but at concentrations below the maximum residue limit
      (MRL). No differences were found in the lindane concentrations between the types
      of fish at each site, but there were two groups of sites that were significantly
      different from one another in terms of lindane concentrations: sites II-IV < site
      I (P <0.05). However, the concentrations of lindane residues in the muscle were
      found to be less than the FAO/WHO (1993) recommended permissible intake and
      should not be of public concern in Mazandaran province.

PMID- 16572713
TI  - Determinants of anemia among pregnant women in Mali.
AB  - BACKGROUND: Anemia in pregnancy remains a major problem in nearly all developing
      and many industrialized countries. In Mali, the subpopulation prevalence and
      etiology of anemia during pregnancy are largely unknown. OBJECTIVE: To examine
      the prevalence and likely etiologies of anemia in pregnancy in a poor urban
      population in Bamako, Mali. METHODS: Pregnant women (n = 190) were selected
      randomly. Hemoglobin, serum iron, and total iron-binding capacity were measured;
      blood smears were examined for Plasmodium falciparum malaria; and single stool
      and urine samples were examined for Schistosoma haematobium and hookworm.
      Gynecologic examinations were performed and interviews conducted to qualitatively
      assess food consumption and other socioeconomic characteristics. Associations
      among mild, moderate, and severe anemia; iron and parasite status; erythrocyte
      sedimentation rates; and the presence of abnormal vaginal discharge were
      evaluated. Differences in hemoglobin and serum iron concentrations, total iron
      binding capacity, and anemia were compared according to trimester of pregnancy
      and between infected and noninfected women. The relative and attributable risks
      of anemia were calculated, and adjusted odds ratios for anemia and low serum iron
      were estimated by multivariate logistic regression. RESULTS: Of the 131 women for
      whom complete data were available, 47% had hemoglobin concentrations below 110
      g/L; 13% had serum iron concentrations below 12 micromol/L; none had transferrin
      saturation values below 16%; 11%, 23%, and 8% harbored P. falciparum, S.
      haematobium, and hookworm, respectively; and 82% had an abnormal vaginal
      discharge. Food restrictions were reported by 45% of the women. Abnormal vaginal
      discharge correlated significantly with anemia (Pearson chi2 = 62.4; p < .01).
      Univariate and multivariate analyses found that infections were strongly
      associated with and predictive of anemia. CONCLUSIONS: Our data suggest that
      infections and food accessibility contribute to the high rates of anemia during
      pregnancy in Mali.

PMID- 16572714
TI  - Urinary iodine concentration of pregnant women and female adolescents as an
      indicator of excessive iodine intake in Sri Lanka.
AB  - BACKGROUND: Mild deficiencies and excesses of iodine have deleterious effects in
      both females and males. The iodine status of the population after implementation
      of the universal salt iodization program in Sri Lanka is not known. OBJECTIVE:
      This cross-sectional study was carried out to assess the iodine status of
      pregnant women and female adolescents, with urinary iodine concentration used as
      the measure of outcome. METHODS: The participants were 100 women in the first
      trimester of pregnancy and 99 female adolescents in Kuliyapitiya, Kurunegala
      District, North-Western Province, Sri Lanka. The urinary iodine concentration was
      measured in a casual urine sample from each subject. The iodate contents of salt
      samples collected from households of the adolescents participating in the study
      were also measured. RESULTS: The median urinary iodine concentration of 185.0
      microg/L and the prevalence of values under 50 microg/L of only 1% among the
      pregnant women indicate adequate iodine intake and optimal iodine nutrition. The
      median urinary iodine concentration (213.1 microg/L) among female adolescents
      indicates a more than adequate iodine intake and a risk of iodine-induced
      hyperthyroidism. Approximately 8% and 4% of the adolescents and pregnant women,
      respectively, had urinary iodine concentrations in the range of mild iodine
      deficiency (51 to 100 microg/L). More than half of the adolescents (56%) and 39%
      of the pregnant women had urinary iodine concentrations higher than optimal. The
      median iodine content in salt samples was 12.7 ppm. Only 20.2% of the samples
      were adequately iodized, and 10.1% of the samples had very high iodine levels.
      CONCLUSIONS: Female adolescents and pregnant women had no iodine deficiency, but
      a considerable proportion of them, especially female adolescents, were at risk
      for iodine-induced hyperthyroidism. There is thus a need for proper monitoring of
      the salt iodization program to achieve acceptable iodine status.

PMID- 16572715
TI  - Fortification of soy sauce using various iron sources: sensory acceptability and
      shelf stability.
AB  - BACKGROUND: Soy sauces are available in different types and grades, which allows
      them to reach consumers of all socioeconomic groups. Ferric sodium
      ethylenediaminetetraacetic acid (NaFeEDTA) has been used for iron fortification
      of soy sauces in some countries, however, its high cost may make it unattractive
      to policymakers and industry. OBJECTIVE: We evaluated the feasibility of using
      more economical iron sources for iron fortification, with soy sauce of various
      types and grades used as a vehicle. METHODS: Seven iron sources were tested for
      their feasibility for fortification of four types of soy sauce: naturally
      fermented in the traditional style, naturally fermented according to large-scale
      industrial formulas 1 and 5, and chemically hydrolyzed at 5 mg per serving (15
      mL, per Thailand's food labeling regulations). Either citric acid or sodium
      citrate was added at 0.1% as a chelator. RESULTS: Five iron sources--ferrous
      sulfate, NaFeEDTA, ferric ammonium citrate, ferrous lactate, and ferrous
      gluconate--did not significantly affect the sensory qualities of the product over
      a period of 3 months (p > .05). Ferrous fumarate and ferrous bisglycinate caused
      unacceptable precipitation. Less than 3% of 260 and 306 commonly cooked foods out
      of 871 and 772 preparations using soy sauces fortified with NaFeEDTA and ferrous
      sulfate, respectively, were found to be different from normal with regard to
      sensory qualities. The cost of fortification was US 0.22 cents to US 3.28 cents
      per bottle (700 mL). CONCLUSIONS: Both naturally fermented and chemically
      hydrolyzed soy sauces could be fortified with all five iron sources. Ferrous
      sulfate is the most appropriate source because of its low cost and acceptable
      sensory characteristics. Soy sauce is a promising vehicle for iron fortification,
      however, the bioavailability of iron in the products examined here needs to be
      evaluated under normal use conditions.

PMID- 16572716
TI  - Development of weaning food from sorghum supplemented with legumes and oil seeds.
AB  - BACKGROUND: The development of low-cost, high-protein food supplements for
      weaning infants from local and readily available raw materials is a constant
      challenge for developing countries. OBJECTIVE: To formulate, develop, and assess
      the nutritive value, acceptability, and keeping quality of sorghum-based staple
      dried flakes as instant weaning foods. METHODS: Weaning blends composed of 42%
      sorghum supplemented with 20% legumes, 10% oil seeds, and 28% additives (sugar,
      oil, skim milk powder, and vanillin) were prepared according to FAO/WHO/UNU
      recommendations and processed in a twin-roller drum dryer. The effects of
      fermentation and of the addition of malt on the nutritive value and functional
      properties of the blends were investigated. RESULTS: The blends were found to
      contain 16.6% to 19.3% protein, 68.7% to 72.7% carbohydrate, 0.9% to 1.3% fiber,
      and 405.8 to 413.2 kcal of energy per 100 g. The iron content of the blends
      ranged from 5.3 to 9.1 mg/100 g, and the calcium content ranged from 150 to 220
      mg/100 g. All blends reconstituted well and formed a soft paste when stirred with
      hot or cold water. The water-holding capacity, wettability, and bulk density were
      within the ranges of corresponding values of commercial weaning foods. Sensory
      attributes, viscosity values, and in vitro digestibility varied among the blends,
      whereas lysing content improved considerably (p < or = .05) for all blends. All
      blends had similar keeping quality, with no signs of spoilage or development of
      off-flavors or colors after 10 months of storage. Most blends remained free of
      aflatoxins. CONCLUSIONS: Legumes and oil seeds can be effectively used in sorghum
      based weaning foods as an acceptable protein and mineral supplement.

PMID- 16572717
TI  - Accuracy of child growth-monitoring weights obtained by commune volunteers in Phu
      Tho Province, Vietnam.
AB  - BACKGROUND: Weight-for-age is a commonly used indicator of the health of children
      and communities. We determined the accuracy of health volunteers' weight
      measurements in a nutrition project in Vietnam. OBJECTIVE: To report the accuracy
      of the volunteers' weight measurements and to assess the likely effect of any
      inaccuracies. METHODS: Save the Children /USA trained health volunteers to weigh
      children (6-36 months old) every other month from December 1999 to August 2000.
      Trained researchers randomly rechecked 257 weights (range, 24-114 per session).
      We computed nondirectional and directional differences between the weights
      measured by volunteers and those measured by researchers. RESULTS: The weights
      recorded by volunteers were lower than those recorded by researchers by an
      average of 30 g (p < .05). Almost all of the error occurred during the first
      weighing session, at which the average weight recorded by volunteers was 280 g
      below that recorded by researchers (p = .01). The error at subsequent weighings
      was minimal (< 20 g below reference at each session). CONCLUSIONS: One-time
      directional error suggests bias. Perhaps some communities (or families)
      influenced the volunteers to report weights lower than those actually observed to
      justify the programmatic food supplements or to give the impression at subsequent
      weighings that the level of malnutrition had been successfully reduced from that
      at the first session. Careful supervision of measurements of weight at baseline
      is essential.

PMID- 16572718
TI  - Prevalence of obesity, overweight, and underweight in Qatari adolescents.
AB  - BACKGROUND: Overweight and obesity have reached epidemic proportions in Arabian
      oil-rich countries and are threatening to become a global epidemic. Excess weight
      has a great impact on the health and quality of life of individuals. However,
      prevalence of underweight in the developing world has shown a decline during the
      last decade. OBJECTIVE: The aim of this cross-sectional study was to determine
      the prevalence of underweight, overweight, and obesity, as measured by body-mass
      index, in a representative sample of adolescents aged 12 to 17 years in the State
      of Qatar. METHODS: Qatari schoolchildren (n = 3,923) from 30 schools in urban and
      semiurban districts responded to a sociodemographic questionnaire. Body-mass
      index was calculated and the prevalence of overweight and obesity was determined
      on the basis of cutoff points of the International Obesity Task Force (IOTF)
      values (above the 85th and 95th percentiles, respectively, for overweight and
      obesity). Underweight was defined on the basis of CDC (Centers for Disease
      Control and Prevention) less than 5th percentile of BMI for age. RESULTS: The
      final sample consisted of 1,968 boys and 1,955 girls. The prevalence of
      underweight, overweight, and obesity was 8.6%, 28.6%, and 7.9%, respectively,
      among adolescent boys and 5.8%, 18.9%, and 4.7% among girls. The prevalence of
      underweight was highest at 16 years of age among boys (10.5%) and at 17 years
      among girls (8.9%). The prevalence of obesity was highest at 12 years of age
      among boys (11.7%) and at 13 years among girls (6.4%). The 95th percentile curve
      for boys was above the IOTF standard curve; the 95th percentile curve for girls
      was below the IOTF curve. CONCLUSIONS: Adolescents living in the State of Qatar
      are at high risk for overweight and obesity. There is a need to establish a
      national program for the prevention and treatment of obesity and related
      complications.

PMID- 16572719
TI  - Food for nutrition: mainstreaming nutrition in WFP.
AB  - Most preventable deaths among hungry people take place outside of emergency
      contexts. In countries not involved in conflicts or natural disasters
      malnutrition is directly implicated in the deaths of millions of children and
      mothers each year. Thus, WFP's great efforts focused on saving lives in
      emergencies should be mirrored by efforts aimed at tackling malnutrition, and
      hence saving lives, beyond emergencies as well. While food sufficiency is not the
      same as good nutrition, food is nevertheless an important part of the nutrition
      equation. New scientific evidence confirms that it is possible to have positive
      nutritional impacts with food aid. Consistent with Strategic Priority No. 3, WFP
      seeks to use food resources to achieve nutritional impacts in three complementary
      ways: a) enhancing the effectiveness and impact of targeted mother and child
      health and nutrition interventions (MCHN) that combine food and appropriate
      nonfood inputs; b) enhancing the nutritional value of WFP food (for instance,
      through micronutrient fortification); and c) enhancing the nutritional impact of
      other WFP (non-MCHN) interventions. These approaches represent a mainstreaming of
      nutrition across WFP's activities. Adoption of evidence-based programming, joint
      interventions with partners, and new project designs offer the promise of greater
      WFP effectiveness and impact in the coming years.

PMID- 16572720
TI  - Nutrition in emergencies: WFP experiences and challenges.
AB  - WFP and its partners have made significant strides in the last decade towards
      tackling malnutrition in emergencies. Since malnutrition is an important
      determinant of mortality, food interventions play a key role in saving lives
      through their impact on the nutrition and health of affected populations.
      Humanitarian interventions aiming to prevent the deterioration, or promote
      recovery, of nutritional status have to be carefully tailored to the nature of
      each crisis and seek to address underlying causes. There are three elements
      crucial to successful action: Ensuring that a nutritionally-appropriate food
      basket is formulated to meet local needs, that it arrives on time and in
      coordinated fashion (not one commodity one month, another the next). Some food
      commodities are needed in small amounts (iodized salt and fortified blended
      foods) but their inclusion and delivery are often critical to positive nutrition
      outcomes. The importance of micronutrients in achieving the goals of emergency
      operations is increasingly well-understood and there is evidence of the need for
      greater use of fortified foods than in the past. Coupling food with essential
      nonfood inputs is important in nutrition programming. Cash resources are required
      by WFP for a variety of nutrition and public health activities, including local
      milling/fortification of cereals, local procurement of fortified blended foods,
      and support for complementary activities such as nutrition education, training,
      and deworming. An ability to offer sustained improvements in nutrition will
      depend on strong collaboration with partners skilled in nutrition and public
      health, including information management. Better linking of emergency programming
      with nonemergency activities is required so that underlying processes
      contributing to serious malnutrition are effectively tackled in the long run.

PMID- 16572721
TI  - Micronutrient fortification: WFP experiences and ways forward.
AB  - Micronutrient deficiencies represent a largely invisible, but often devastating,
      form of malnutrition that is particularly prevalent among WFP's beneficiary
      populations already lacking sufficient food. Known effects of micronutrient
      deficiencies include impaired physical and mental growth among children, iron
      deficiency anemia, maternal mortality, low adult labor productivity and
      blindness. WFP makes important, often pioneering contributions to overcoming such
      deficiencies through: Careful attention to micronutrients in needs assessment and
      ration planning, Delivering fortified foods, particularly to nutritionally
      vulnerable groups, on an increasingly large scale, Promotion and use of locally
      produced and fortified commodities in more than a dozen low income, food deficit
      countries, Advocacy for fortification at national and international policy
      levels. Important activities in local processing and fortification have recently
      taken place in countries like Zambia, Angola, Bangladesh, India, Nepal, and in
      the context of the regional southern Africa drought emergency. Each case
      demonstrates that where micronutrient deficiencies are an operational concern
      local fortification is possible, albeit challenging. Several ongoing assessments
      of the impact of such initiatives suggest important nutritional benefits. That
      said, challenges remain in terms of technical and managerial capacity
      constraints, the need for systematic compliance with procurement specifications
      and quality control, clearer policies on micronutrient content labeling, and the
      need for cash resources to support many aspects associated with local processing
      and fortification activities.

PMID- 16572722
TI  - The 2005 Abraham Horwitz Award for Leadership in Inter-American Health address:
      Dr. Ricardo Uauy.

PMID- 16572723
TI  - Defined benefit plan freezes: who's affected, how much, and replacing lost
      accruals.

PMID- 16572725
TI  - Toxoplasma gondii-derived heat shock protein 70 stimulates maturation of murine
      bone marrow-derived dendritic cells via Toll-like receptor 4.
AB  - Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70) induced maturation of
      bone marrow-derived dendritic cells (DCs) of wild-type (WT) C57BL/6 mice as
      evidenced by an increase in surface expression of MHC class I and II molecules
      and costimulatory molecules such as CD40, CD80, and CD86. Functionally, decreased
      phagocytic ability and increased alloreactive T cell stimulatory ability were
      observed in T.g.HSP70-stimulated DCs. These phenotypic and functional changes of
      T.g.HSP70-stimulated DCs were demonstrated in Toll-like receptor (TLR) 2- and
      myeloid differentiation factor 88 (MyD88)-deficient but not TLR4-deficient
      C57BL/6 mice. DCs from WT and TLR2-deficient but not TLR4-deficient mice produced
      IL-12 after T.g.HSP70 stimulation. T.g.HSP70-stimulated DCs from WT, TLR2
      deficient, and MyD88-deficient, but not TLR4-deficient mice expressed IFN-beta
      mRNA. Thus, T.g.HSP70 stimulates murine DC maturation via TLR4 through the MyD88
      independent signal transduction cascade.

PMID- 16572724
TI  - Antibodies against heat shock proteins in environmental stresses and diseases:
      friend or foe?
AB  - Heat shock proteins (Hsps) can be found in two forms, intracellular and
      extracellular. The intracellular Hsps are induced as a result of stress and have
      been found to be cytoprotective in many instances due to their chaperone
      functions in protein folding and in protein degradation. The origin and role of
      extracellular Hsps is less clear. Although they were suspected originally to be
      released from damaged cells (necrosis), their presence in most normal individuals
      rather suggests that they have regulatory functions in circulation. As
      immunodominant molecules, Hsps can stimulate the immune system, leading to the
      production of autoantibodies recognizing epitopes shared by microbial and human
      Hsps. Thus, extracellular Hsps can influence the inflammatory response as
      evidenced by the production of inflammatory cytokines. Antibodies to Hsps have
      been found under normal conditions but seem to be increased in certain stresses
      and diseases. Such antibodies could regulate the inflammatory response positively
      or negatively. Here, we review the literature on the findings of antibodies to
      Hsps in situations of environmental or occupational stress and in a number of
      diseases and discuss their possible significance for the diagnosis, prognosis, or
      pathogenesis of these diseases.

PMID- 16572726
TI  - A genomewide analysis of genes for the heat shock protein 70 chaperone system in
      the ascidian Ciona intestinalis.
AB  - Molecular chaperones play crucial roles in various aspects of the biogenesis and
      maintenance of proteins in the cell. The heat shock protein 70 (HSP70) chaperone
      system, in which HSP70 proteins act as chaperones, is one of the major molecular
      chaperone systems conserved among a variety of organisms. To shed light on the
      evolutionary history of the constituents of the chordate HSP70 chaperone system
      and to identify all of the components of the HSP70 chaperone system in ascidians,
      we carried out a comprehensive survey for HSP70s and their cochaperones in the
      genome of Ciona intestinalis. We characterized all members of the Ciona HSP70
      superfamily, J-proteins, BAG family, and some other types of cochaperones. The
      Ciona genome contains 8 members of the HSP70 superfamily, all of which have human
      and protostome counterparts. Members of the STCH subfamily of the HSP70 family
      and members of the HSPA14 subfamily of the HSP110 family are conserved between
      humans and protostomes but were not found in Ciona. The Ciona genome encodes 36 J
      proteins, 32 of which belong to groups conserved in humans and protostomes. Three
      proteins seem to be unique to Ciona. J-proteins of the RBJ group are conserved
      between humans and Ciona but were not found in protostomes, whereas J-proteins of
      the DNAJC14, ZCSL3, FLJ13236, and C21orf55 groups are conserved between humans
      and protostomes but were not found in Ciona. J-proteins of the sacsin group seem
      to be specific to vertebrates. There is also a J-like protein without a conserved
      HPD tripeptide motif in the Ciona genome. The Ciona genome encodes 3 types of BAG
      family proteins, all of which have human and protostome counterparts (BAG1, BAG3,
      and BAT3). BAG2 group is conserved between humans and protostomes but was not
      found in Ciona, and BAG4 and BAG5 groups seem to be specific to vertebrates.
      Members for SIL1, UBQLN, UBADC1, TIMM44, GRPEL, and Magmas groups, which are
      conserved between humans and protostomes, were also found in Ciona. No Ciona
      member was retrieved for HSPBP1 group, which is conserved between humans and
      protostomes. For several groups of the HSP70 superfamily, J-proteins, and other
      types of cochaperones, multiple members in humans are represented by a single
      counterpart in Ciona. These results show that genes of the HSP70 chaperone system
      can be distinguished into groups that are shared by vertebrates, Ciona, and
      protostomes, ones shared by vertebrates and protostomes, ones shared by
      vertebrates and Ciona, and ones specific to vertebrates, Ciona, or protostomes.
      These results also demonstrate that the components of the HSP70 chaperone system
      in Ciona are similar to but simpler than those in humans and suggest that changes
      of the genome in the lineage leading to humans after the separation from that
      leading to Ciona increased the number and diversity of members of the HSP70
      chaperone system. Changes of the genome in the lineage leading to Ciona also seem
      to have made the HSP70 chaperone system in this species slightly simpler than
      that in the common ancestor of humans and Ciona.

PMID- 16572727
TI  - Inducible heat shock protein 70 expression as a potential predictive marker of
      metastasis in breast tumors.
AB  - Heat shock protein (Hsp)-peptide complexes purified from tumors can prime the
      immune system against tumor antigens, but how they contribute to the generation
      of immune responses against naturally occurring tumors is unknown. Murine tumors
      expressing high amounts of Hsp70 are preferentially rejected by the immune
      system, suggesting that low Hsp70 expression is advantageous for tumor growth in
      the host. To determine whether Hsp70 was differentially expressed in human
      tumors, inducible Hsp70 expression was quantitatively (by Western blot) and
      qualitatively (by immunohistology) analyzed in 53 biopsies of tumor and normal
      breast tissue. The mean expression of inducible Hsp70 was significantly higher in
      tumor compared with normal tissue (U = 899.0; P = 0.0033). However, a significant
      negative association of the amount of Hsp70 expressed by tumor tissue was found
      with metastasis (r = -0.309; P = 0.05). After 3 years, follow-up analysis
      determined that 7 of the 53 patients relapsed, and 5 died. Hsp70 expression in
      tumor (but not normal) cells was significantly lower in relapse patients and
      patients with metastatic disease than in patients with no relapse or metastasis.
      Together, these observations support the hypothesis that Hsp70 plays a role in
      tumor expansion in vivo, and tumors that downregulate it may be able to evade
      immunosurveillance and grow.

PMID- 16572728
TI  - Heat shock protein 70 binds its own messenger ribonucleic acid as part of a gene
      expression self-limiting mechanism.
AB  - Expression of heat shock proteins is a cellular response to a variety of
      stressors. HSP70, the major stress-induced heat shock protein, is involved in
      repair and protection after the insult. However, the prolonged presence of this
      protein is detrimental. Consequently, Hsp70 expression must be tightly regulated.
      We have previously shown an increase in the degradation of Hsp70 messenger
      ribonucleic acid (mRNA) paralleling the accumulation of HSP70. Incubation of
      cells with transcriptional and translational inhibitors after heat shock resulted
      in a significant reduction in Hsp70 mRNA degradation. These observations suggest
      that newly synthesized, stress-induced factors might be involved in the decay of
      Hsp70 mRNA. We found that HSP70 binds directly to Hsp70 mRNA, as demonstrated by
      immunoprecipitation. This observation was confirmed by RNA gel-shift assays.
      These results are evidence for a novel and likely direct interaction between
      HSP70 and Hsp70 mRNA in cells after stress. This interaction may be part of a
      self-limiting mechanism to reduce HSP70 production, thus avoiding potential toxic
      effects of this protein in the absence of stress.

PMID- 16572729
TI  - Differences in the chaperone-like activities of the four main small heat shock
      proteins of Drosophila melanogaster.
AB  - The Drosophila melanogaster family of small heat shock proteins (sHsps) is
      composed of 4 main members (Hsp22, Hsp23, Hsp26, and Hsp27) that display distinct
      intracellular localization and specific developmental patterns of expression in
      the absence of stress. In an attempt to determine their function, we have
      examined whether these 4 proteins have chaperone-like activity using various
      chaperone assays. Heat-induced aggregation of citrate synthase was decreased from
      100 to 17 arbitrary units in the presence of Hsp22 and Hsp27 at a 1:1 molar ratio
      of sHsp to citrate synthase. A 5 M excess of Hsp23 and Hsp26 was required to
      obtain the same efficiency with either citrate synthase or luciferase as
      substrate. In an in vitro refolding assay with reticulocyte lysate, more than 50%
      of luciferase activity was recovered when heat denaturation was performed in the
      presence of Hsp22, 40% with Hsp27, and 30% with Hsp23 or Hsp26. These differences
      in luciferase reactivation efficiency seemed related to the ability of sHsps to
      bind their substrate at 42 degrees C, as revealed by sedimentation analysis of
      sHsp and luciferase on sucrose gradients. Therefore, the 4 main sHsps of
      Drosophila share the ability to prevent heat-induced protein aggregation and are
      able to maintain proteins in a refoldable state, although with different
      efficiencies. The functional reasons for their distinctive cell-specific pattern
      of expression could reflect the existence of defined substrates for each sHsp
      within the different intracellular compartments.

PMID- 16572730
TI  - Conformational changes resulting from pseudophosphorylation of mammalian small
      heat shock proteins--a two-hybrid study.
AB  - The human genome codes for 10 so-called mammalian small heat shock or stress
      proteins (sHsp) with the various tissues expressing characteristic sets of sHsps.
      Most sHsps interact with each other and form homo- and heterooligomeric
      complexes. Some of the sHsps are phosphoproteins in vivo, and phosphorylation has
      been implicated in the regulation of complex size and composition. In this study,
      we analyze, by the 2-hybrid method, the reporter gene activation pattern of
      several sHsp pairs that previously have been demonstrated to interact. We show
      that pseudophosphorylation (mimicry of phosphorylation) of the homologous
      phosphorylation sites Ser15 and Ser16 in Hsp27 and Hsp20, respectively, modulates
      characteristics of these sHsps that can be detected by their ability to activate
      reporter genes in suitable 2-hybrid assays. Pseudophosphorylation of the
      separated N-terminus of Hsp27 alone is not sufficient for the activation of the
      reporter genes, whereas the separated C-terminus is sufficient. We conclude that
      pseudophosphorylation of Hsp27 and Hsp20 at their N-termini results in
      conformational changes that can be detected by their interaction with other
      sHsps. Pseudophosphorylation of alphaB-crystallin at Ser19, in contrast, had no
      detectable consequences.

PMID- 16572731
TI  - Inhibition of apoptosis by p26: implications for small heat shock protein
      function during Artemia development.
AB  - p26, an abundantly expressed small heat shock protein, is thought to establish
      stress resistance in oviparously developing embryos of the crustacean Artemia
      franciscana by preventing irreversible protein denaturation, but it might also
      promote survival by inhibiting apoptosis. To test this possibility, stably
      transfected mammalian cells producing p26 were generated and their ability to
      resist apoptosis induction determined. Examination of immunofluorescently stained
      transfected 293H cells by confocal microscopy demonstrated p26 is diffusely
      distributed in the cytoplasm with a minor amount of the protein in nuclei. As
      shown by immunoprobing of Western blots, p26 constituted approximately 0.6% of
      soluble cell protein. p26 localization and quantity were unchanged during
      prolonged culture, and the protein had no apparent ill effects on transfected
      cells. Molecular sieve chromatography in Sepharose 6B revealed p26 oligomers of
      about 20 monomers, with a second fraction occurring as larger aggregates. A
      similar pattern was observed in sucrose gradients, but overall oligomer size was
      smaller. Mammalian cells containing p26 were more thermotolerant than cells
      transfected with the expression vector only, and as measured by annexin V
      labeling, Hoescht 33342 nuclear staining and procaspase-3 activation, transfected
      cells effectively resisted apoptosis induction by heat and staurosporine. The
      ability to confer thermotolerance and limit heat-induced apoptosis is important
      because Artemia embryos are frequently exposed to high temperature in their
      natural habitat. p26 also blocked apoptosis in transfected cells during drying
      and rehydration, findings with direct relevance to Artemia life history
      characteristics because desiccation terminates cyst diapause. Thus, in addition
      to functioning as a molecular chaperone, p26 inhibits apoptosis, an activity
      shared by other small heat shock proteins and with the potential to play an
      important role during Artemia embryo development.

PMID- 16572732
TI  - Induction of the 72-kilodalton heat shock protein and protection from ultraviolet
      B-induced cell death in human keratinocytes by repetitive exposure to heat shock
      or 15-deoxy-delta(12,14)-prostaglandin J2.
AB  - It has been demonstrated that hyperthermia protects keratinocytes from
      ultraviolet B (UVB)-induced cell death in culture and in vivo. This effect is
      mediated by the antiapoptotic effect of heat shock proteins that are transiently
      induced after exposure to heat at sublethal temperatures. Consequently, induction
      of Hsp has been proposed as a novel means of photoprotection. However, in the
      face of daily UVB exposure of human skin in vivo, this approach would not be
      useful if keratinocytes become less sensitive to Hsp induction with repeated
      exposure to the inducing agent. The aim of this study was to investigate whether
      repeated exposure to hyperthermia or to the stress protein activating
      cyclopentenone prostaglandin 15-deoxy-delta(12,14)-prostaglandin J2 (15dPGJ2)
      leads to adaptation of the cells, attenuation of the heat shock response, and
      abrogation of the protective effect. Normal human epidermal keratinocytes (NHEK)
      and the carcinoma-derived cell line A431 were exposed to either 42 degrees C or
      to 15dPGJ2 for 4 hours at 24-hour intervals for 4 consecutive days. The
      intracellular level of the 72-kDa heat shock protein (Hsp72) was determined by
      enzyme-linked immunosorbent assay (ELISA). Cells were exposed to UVB from a metal
      halide source after the last heat or 15dPGJ2 treatment, and survival was
      determined 24 hours after exposure by a MTT assay. Our results demonstrate that
      (1) heat shock and 15dPGJ2 are potent inducers of Hsp72 expression and lead to
      increased resistance to UVB-induced cell death in human keratinocytes; (2) re
      exposure to heat shock leads to a superinduction without attenuation of the
      absolute increase in Hsp72 and of its UVB-protective effect; (3) the UVB
      tolerance induced by 15dPGJ2 is enhanced by repeated exposure without a further
      increase of Hsp72; (4) repeated heat shock and 15dPGJ2 up to a concentration of 1
      microg/mL have no influence on cell growth over a period of 4 days. We conclude
      that through repeated exposure to Hsp-inducing factors, stress tolerance can be
      maintained without additional toxicity in human keratinocytes. These results
      provide a basis for the development of nontoxic Hsp inducers that can be
      repeatedly applied without loss of effect.

PMID- 16572733
TI  - Heat stress enhances recovery of hepatocyte bile acid and organic anion
      transporters in endotoxemic rats by multiple mechanisms.
AB  - Heat stress (HS) reduces the many sequelae of lipopolysaccharide (LPS)-induced
      endotoxemia. Without HS, endotoxins have been shown to induce a transcriptional
      down-regulation of hepatocyte transport proteins for bile acids and organic
      anions. We performed experiments in isolated perfused rat livers at various times
      after LPS administration with and without HS pretreatment to determine whether HS
      would correct deficient transport of bromosulfophthalein (BSP). Possible
      mechanisms involved were investigated in livers from intact animals. In isolated
      perfused livers, LPS injection reduced BSP excretion to 48% compared with saline
      injected controls (P < 0.01). When HS was applied 2 hours prior to LPS, BSP
      excretion increased to 74% of controls (P < 0.05 vs LPS and controls). Expression
      of the basolateral (Oatp1a1) and canalicular (Mrp2) organic anion transporter
      involved in the transport of BSP recovered more rapidly when HS preceded LPS
      application. Recovery of mRNA levels of these transporters occurred also earlier.
      Coimmunoprecipitation experiments and immunoelectron microscopy using a double
      immunogold labeling of heat shock protein 70 (HSP70) and various hepatocyte
      transporters suggested colocalization with HSP70 for the canalicular bile acid
      transporter (Bsep) in the subcanalicular space. In contrast, no colocalization
      was shown for Ntcp and anion transporters. In conclusion, we could show that HS
      enhances recovery of organic anion transporters and bile acid transporters
      following endotoxemia. Faster recovery of mRNA seems to be a key mechanism for
      anion transporters, whereas physical interaction with HSP70 plays a role in
      preservation of bile acid transporters. This interaction of HSP70 and canalicular
      transporters occurs only in pericanalicular vesicles but not when the protein is
      integrated into the plasma membrane.

PMID- 16572734
TI  - Birth defects and anti-heat shock protein 70 antibodies in early pregnancy.
AB  - Abstract It has been suggested that induction of the heat shock response in the
      mammalian embryo during the critical period of organogenesis can result in
      anatomical malformation. We measured serum heat shock protein 70 (Hsp70), anti
      Hsp70, and anti-Hsp60 in samples taken from expectant mothers at 16 weeks
      gestation. Samples from women whose babies were born with a birth defect (n = 30)
      were compared with controls who gave birth to healthy babies (n = 46). Anti-Hsp70
      levels were significantly elevated in patients who later gave birth to babies
      with cleft lip or palate or neurological abnormalities (n = 10): 260 (223-406)
      microg/mL compared to 150 (88-207) microg/mL in controls (P < 0.001). No
      significant differences were found in serum Hsp70 and anti-Hsp60 levels between
      cases and controls. This finding of increased maternal anti-Hsp70 in patients who
      later gave birth to babies with these abnormalities suggests a previous stressful
      event may have contributed to the pathogenesis. Further work is required to
      determine whether Hsp70 has a direct or indirect role in this pathogenesis or
      whether anti-Hsp70 is simply a marker of a prior increase in Hsp70 due to a
      physiological stress that itself resulted in the damage. This work is consistent
      with previous studies showing a buffering role for Hsps in evolution.

PMID- 16572735
TI  - The efficacy and safety of 30 mg fexofenadine HCl bid in pediatric patients with
      allergic rhinitis.
AB  - Allergic rhinitis is one of the most common chronic disorders in children. It is
      also one of the most common causes of absence from school. This study reports on
      the efficacy and safety of a twice-daily oral dose of fexofenadine HCl 30 mg in
      Asian children aged 6-11 years diagnosed with seasonal or perennial allergic
      rhinitis. A total of 100 children with a history of allergic rhinitis for more
      than one year and a positive prick skin test response to at least one of the
      common aeroallergens in Thailand were enrolled in this multi-center, open-label,
      non comparative study. The severity of individual symptoms such as sneezing,
      rhinitis, etc. and adverse events were recorded in diary cards by the patients in
      form of scores as well as by the investigator at each visit. The total symptom
      score (TSS) with or without blocked nose at baseline, week 1 and week 2 was
      recorded. The TSS was defined as the sum of the individual symptom scores except
      for the nasal blockage score, as nasal blockage was not expected to respond to
      antihistamine treatment. Only patients with a total symptom score > or = 6 were
      included in the study. There was a statistically significant improvement at p <
      0.01 for the TSS with or without blocked nose and for each symptom score such as
      blocked nose, sneezing, rhinorrhea, itchy nose/palate and/or throat, and
      itchy/watery/red eyes from baseline to week 1 and week 2. Additionally, there was
      a statistically significant improvement between week 1 and week 2 for itchy
      nose/palate and/or throat and itchy/watery/red eyes (p < 0.05). The Kappa measure
      of agreement was statistically significant at p < 0.001 between investigator's
      and patient's/parent's assessment, indicating the same degree of satisfaction
      with the overall effectiveness of the treatment. Fexofenadine 30 mg bid is
      effective in reducing the total symptom score of allergic rhinitis including
      blocked nose and is generally well tolerated. It is not cardiotoxic and is safe
      for pediatric patients as young as 6 years of age.

PMID- 16572736
TI  - Food induced urticaria in children.
AB  - We conducted a prospective study at King Chulalongkorn Memorial Hospital, from
      June 2001 to November 2003, to identify the contribution of food allergy to
      urticaria in children. During the study period, 100 children with urticaria were
      enrolled, 36 of whom had a history suspicious of food allergy. Fifteen of 100
      patients had fever (9 from upper respiratory tract infections, 4 from diarrhea
      and 2 from skin infections). A skin prick test (SPT) was positive in 15 of the 36
      children who were suspected of having food allergy; 5 patients out of the
      positive SPT group had anaphylaxis due to food (2 from cow milk, 2 from wheat and
      1 from egg). Six patients in the positive SPT group had a negative food challenge
      test (4 from open challenges and 2 from double-blind placebo-controlled food
      challenges [DBPCFC]). The other 4 patients of the positive SPT group refused the
      food challenge test. The parents of a patient who had urticaria from egg refused
      the skin prick test; an oral challenge test confirmed the diagnosis of egg
      allergy. One of the 21 patients that had a negative SPT had shrimp allergy proven
      by DBPCFC. Of the 64 patients who had no history related to food, SPT was done in
      27 patients and revealed a positive result in 7 patients, all of whom had a
      negative food challenge test (4 with open challenge and 3 with DBPCFC). Urticaria
      from food was found in 7% and was suspected in another 4% of the patients. Severe
      reactions to food like anaphylaxis may occur. SPT alone is not adequate in making
      the diagnosis of food allergy; it must be confirmed by a food challenge test.
      Thirty percent of patients that did not have a history related to food had false
      positive SPT. Without a history suspicious of food allergy, SPT yields only
      minimal benefit.

PMID- 16572737
TI  - Plasma soluble intercellular adhesion molecule-1 (sICAM-1) in pediatric ARDS
      during high frequency oscillatory ventilation: a predictor of mortality.
AB  - Soluble intercellular adhesion molecule-1 (sICAM-1), an important adhesion
      molecule that mediates leukocyte-endothelial interaction, has been identified as
      a marker for the outcome of acute respiratory tract infection. We postulate that
      plasma ICAM-1 may be a valuable marker for both biological and clinical severity
      of acute respiratory distress syndrome (ARDS). Sixteen pediatric patients (> 1
      month and < 15 years of age) diagnosed with ARDS were recruited from the
      Pediatric Intensive Care Unit at King Chulalongkorn Memorial University Hospital,
      Bangkok. The patients were randomized to receive either high frequency
      oscillatory ventilation (HFOV) or conventional mechanical ventilation. Plasma
      sICAM-1 was measured by enzyme linked immunosorbent assay (ELISA) on days 1, 3, 5
      and 7 of ARDS. Plasma sICAM-1 levels in survivors and non-survivors of the HFOV
      and conventional treatment groups were compared. Nine and 7 patients constituted
      the control group receiving conventional treatment and HFOV group, respectively.
      Overall nine patients survived. The patients in the HFOV group had a better
      chance of survival compared to the controls (71% versus 31.5%), but it was not
      statistically significant (p = 0.2). The overall mortality was 45.7%. The mean
      plasma sICAM-1 levels (n = 13/16) were significantly elevated among non-survival
      patients as compared to survival patients at all time points, which indicates
      that an unfavorable outcome in ARDS is related to the degree of epithelial and
      endothelial alveolar cell injury. The elevation of plasma slCAM-1 on day 3
      provided the best predictor of mortality (likelihood ratio 11.9, p < 0.001). It
      was concluded that HFOV facilitated a potentially better outcome compared to
      conventional treatment and it was associated with less lung injuries evidenced by
      lower plasma sICAM-1.

PMID- 16572738
TI  - Sputum induction in corticosteroid-dependant asthmatics: risks and airway
      cellular profile.
AB  - Sputum induction with nebulized hypertonic saline is increasingly being used to
      evaluate airway inflammation. We investigated the procedure-associated risk in 16
      asthmatics that were still symptomatic despite on high doses of regular
      corticosteroid (CS) therapy (7 on daily inhaled CS > or = 800 microg budesonide
      or equivalent; 9 on additional daily oral CS) and their sputum cellular profile.
      For comparison, 12 mild stable asthmatics and 10 normal healthy subjects were
      included. All subjects inhaled 3%, 4% and 5% hypertonic saline sequentially via
      ultrasonic nebulizer as a means to induce sputum. Maximal percentage fall of
      Forced Expiratory Volume on One Second (FEV1) during sputum induction was
      significantly greater in CS-dependent asthmatics (median % [IQR]: 16.0 [11.0
      32.3]) than in mild asthmatics (5.3 [4.2-10.8], p = 0.002] and in normal subjects
      (4.6 [3.4-6.4]), p = 0.0001). The maximal percentage FEV1 fall was inversely
      correlated with baseline FEV1 (Rs= -0.69; p < 0.0001). Compared to mild
      asthmatics, induced sputum from CS-dependant asthmatics had proportionately fewer
      eosinophils (2.2 [0.8-7.0] versus 23.3% [10.7-46.3], p = 0.003) and greater
      neutrophils (64.2 [43.9-81.2] versus 28.7 [19.0-42.6], p = 0.009). Sputum
      neutrophils showed a significant inverse correlation to FEV1 (Rs = -0.51, p =
      0.01). We concluded that sputum induction using nebulized hypertonic saline
      should be performed with caution in CS-dependant asthmatics. The airway cellular
      profile observed suggests that the immunopathology underlying CS-dependant
      asthmatics may be different or a consequence of CS therapy.

PMID- 16572739
TI  - Clinical presentation and outcome of Thai patients with chronic lymphocytic
      leukemia: retrospective analysis of 184 cases.
AB  - Chronic lymphocytic leukemia (CLL), which is the most common leukemia in adult
      population in the Western world, is surprisingly rare in Thailand. The objective
      of our study was to retrospectively analyze the clinical presentations and
      outcome of a large cohort of Thai CLL patients diagnosed at a single institution
      in Bangkok, Thailand, from 1963-1998. One hundred and eighty-four patients were
      included in the study. The most frequent age group was 60-80 years old with the
      male to female ratio of 2:1. Only 12% of patients were younger than the age of
      50. Most patients were from the central agricultural region of Thailand. Clinical
      findings at presentation included splenomegaly (64%), lymphadenopathy (60%),
      anemia (54%), hepatomegaly (49%), fatigue (39%), weight loss (33%), fever (21%),
      thrombocytopenia (18%), and anorexia (8%). Only 8% of Thai CLL patients were
      asymptomatic at presentation. The majority of patients were categorized as stages
      III and IV with the median survival of 20 months and 8 months, respectively.
      Infection was the most common cause of death, particularly in the elderly
      patients who had comorbid illnesses. Twenty-two percent of the patients had
      associated autoimmune disorders. The unfavorable prognostic factors observed were
      older age (> 70 years), weight loss and hepatosplenomegaly. We concluded that the
      age and gender of Thai CLL patients were similar to those of the Western
      countries but our patients came to medical attention at a later and more advanced
      stage. Prospective studies at a multi-center level in Thailand should be pursued
      to investigate further the genetic and epidemiologic nature of Thai CLL patients.

PMID- 16572740
TI  - Evaluation of human IgG subclass antibodies in the serodiagnosis of
      Paragonimiasis heterotremus.
AB  - Immunoglobulin G subclass antibodies (IgG1, IgG2, IgG3, and IgG4) responses to
      the excretory-secretory antigens of the lung fluke, Paragonimus heterotremus,
      were analyzed using the immunoblotting technique in an attempt to further improve
      the sensitivity and specificity for serodiagnosis of human paragonimiasis. Serum
      samples from patients with proven paragonimiasis, from patients with other
      parasitic infections, pulmonary tuberculosis and from healthy counterparts were
      analyzed. The results indicate that immunoblotting for the detection of IgG4
      antibodies to an excretory-secretory product of P. heterotremus of an approximate
      molecular mass of 31.5 kDa, is the most reliable test. It gives accuracy,
      sensitivity, specificity, and positive and negative predictive values of 97.6%,
      100%, 96.9%, 90% and 100%, respectively.

PMID- 16572741
TI  - Detection of amino acids in human nasal mucosa using microdialysis technique:
      increased glutamate in allergic rhinitis.
AB  - Amino acids, the smaller basic biochemical units of neuropeptides, have not been
      evaluated in the nasal cavity. The purpose of this study was to measure the
      concentration of neurotransmitting amino acids of the central nervous system,
      glutamate, aspartate, serine, taurine (2-aminoethane sulfonic acid; a
      conditionally essential amino acids), and GABA (gamma-amino-butyric acid; an
      amino acid produced in the brain), in nasal mucosa of allergic rhinitis patients
      and normal controls using a microdialysis technique. A microdialysis probe
      appropriate for use on human nasal mucosa was developed using Cuprophan hollow
      fiber. Glutamate concentration in allergy group was significantly higher (p =
      0.004) than in control group, while the concentrations of the other four amino
      acids showed no significant difference between the two groups. Our findings and
      review of the literature suggest that glutamate is one of the most potent
      neurotransmitters associated with the parasympathetic nerve in the nasal cavity,
      and that the microdialysis technique is useful in studying the pharmacokinetics
      in situ and local organ chemistry of the nasal cavity.

PMID- 16572742
TI  - Disseminated Bacille Calmette-Guerin disease as the initial presentation of X
      linked severe combined immunodeficiency--a case report.
AB  - Bacille Calmette-Guerin (BCG) vaccination is used to prevent severe M.
      tuberculosis infection. It has been used in many countries for a long time.
      However, complications do occur, including localized abscesses, regional
      lymphadenitis and disseminated disease. The latter is often associated with
      underlying immunodeficiency. We report an 8-month-old male infant presenting with
      cough and fever who had had a generalized pigmented skin rash for one month. Skin
      biopsy revealed mycobacterial infection, but his response to treatment was poor
      and he had a persistent mild fever. Immunological studies revealed an IgG of 49
      mg/dl, IgA 4 mg/dl, IgM 28 mg/dl, IgE < 1 mg/dl, CD3 1.1%, CD4 0.6%, CD8 0.6%,
      CD19 93.9%, CD57 1.1%, activated T cells 0.9%, and CH50 < 6.3%. These findings
      are compatible with the diagnosis of T(-)B(+)NK- severe combined
      immunodeficiency. Sequence analysis was performed and showed the presence of
      missense mutation in IL2Rgamma gene. An X-linked recessive inheritance pattern
      was proved by sequence analysis of his mother and grandmother. In order to
      identify the strain of the microorganism, we reviewed pathology of the skin
      biopsy which consisted of diffuse histiocytic infiltrate with poorly formed
      granulomas and no necrosis and used polymerase chain reaction (PCR) with the
      stain-positive clinical specimen and verify the organism found in the child's
      biopsy as M. bovis BCG strain. The diagnosis of disseminated BCG disease must be
      considered in any infant with cutaneous mycobacterial lesions, especially with
      atypical histologic findings. Such a patient's immunologic status should be
      evaluated and further family study is suggested. A high index of suspicion is
      needed to make a timely diagnosis, as early intervention with intensive treatment
      and bone marrow transplantation may be life-saving.

PMID- 16572743
TI  - Hereditary angioedema: a family study.
AB  - Hereditary angioedema (HAE) is a rare, life-threatening, autosomal dominant
      disease characterized by recurrent episodes of angioedema, and caused by a
      deficiency of the plasma protein C1-esterase inhibitor (C1-INH). Clinical
      manifestation of HAE may first develop during childhood but typically presents
      around puberty with nonpruritic and non-pitting edema of the subcutaneous and
      mucosal tissues. Up to now, there has been no published report of HAE case in
      Taiwan. We reported a 33 year-old female patient who had recurrent painful
      swelling of face and hands since 27 years of age. She first suffered from sudden
      onset of painful swelling of the eyelids and lips in August 1998 when she was
      pregnant for the first time. Subsequently, similar episodes recurred for a few
      times. Her blood test disclosed that her C3 and C4 were 125 mg/dl and 6 mg/dl,
      respectively. Her uncle died of laryngeal edema at the age of 30 years. Her
      father and elder brother also had the similar history of recurrent facial and
      hand swelling. The C4 levels of her elder brother were 6 mg/dl and 13.3 mg/dl on
      two separate occasions. The C1-INH antigen serum level and functional assay of
      the index patient and ten other family members were studied. A total of seven
      members of the family were confirmed to have type 1 HAE as evidenced by the low
      C4 and low C1-INH antigenic level and functional activity. Two of the seven cases
      were asymptomatic up to the date of our report.

PMID- 16572744
TI  - Immune dysfunction in Australian Aborigines.
AB  - An examination of the prevalence and phenotype of immune disorders in different
      ethnic groups may provide important clues to the etiopathogenesis of these
      disorders. Whilst still conjectural the restricted and somewhat unique
      polymorphisms of the MHC (and other genetic loci involving host defences) of the
      Australian Aborigines may provide an explanation for their apparent heightened
      susceptibility to newly encountered infections and their resistance to many
      (auto) immune and allergic disorders. In comparison with non-Aboriginal
      Australians, Australian Aborigines have heightened frequencies of rheumatic
      fever, systemic lupus erythematosus, various infections and post-streptococcal
      glomerulonephritis. In contrast various autoimmune disorders (e.g. rheumatoid
      arthritis, multiple sclerosis, CREST, biliary cirrhosis, coeliac disease,
      pernicious anaemia, vitiligo), B27 related arthropathies, psoriasis,
      lymphoproliferative disorders and atopic disorders appear infrequent or absent.
      Similarly various autoantibodies occur with increased or diminished frequency.
      With continuing racial admixture, social deprivation and deleterious lifestyles
      of these people it is likely that further changes in both the frequencies and
      phenotype of these immune disorders will occur. It is only with a full
      understanding of the pathogenic mechanisms involved in these immune disorders
      that meaningful and clinical relevant interventions will be possible.

PMID- 16572745
TI  - Restrictive protocols and contracted thinking.

PMID- 16572746
TI  - How do surrogate decision makers describe hospice? Does it matter?
AB  - We interviewed 71 surrogate decision makers of older, chronically ill veterans to
      explore their knowledge of hospice and their role in helping loved ones access
      hospice services. We asked them to describe hospice and any previous hospice
      experiences. Of the group, 24 percent with hospice experience and 14 percent
      without hospice experience correctly described three key aspects of hospice: who
      hospice cares for, where the care is provided, and the goal of the care.
      Additionally, we found evidence that surrogates who correctly described the three
      key aspects of hospice were inclined to pursue hospice care for loved ones in the
      future, and surrogates who provided less complete descriptions of hospice might
      not access it. Since surrogates often help dying patients access care, incomplete
      knowledge of hospice may be an important barrier to hospice services. We advocate
      that clinicians discuss the three key aspects of hospice during routine advance
      care planning sessions with patients and their future surrogate decision makers.

PMID- 16572747
TI  - Music thanatology: prescriptive harp music as palliative care for the dying
      patient.
AB  - Music thanatology represents an emerging area in which the raw materials of
      music, usually harp and/or voice, assist and comfort the dying patient. During
      prescriptive "music vigils, " the clinician-musician carefully observes
      physiological changes, cues, and breathing patterns, thereby synchronizing the
      music to reflect or support the patient's physiology and overall condition. Using
      data collected from 65 patients, this study was designed to assess the
      effectiveness of prescriptive harp music on selected palliative care outcomes
      using a sample of de-identified data forms from past music vigils. Patients were
      administered a 25- to 95-minute intervention of prescriptive harp music. Data
      collected included vital signs and observational indicators before (Ti) and after
      (T2) the vigil. Patients were more likely to experience decreased levels of
      agitation and wakefulness while also breathing more slowly and deeply with less
      effort at the conclusion of the music vigil. Results from this study suggest that
      a prescriptive vigil conducted by a trained music thanatologist could provide an
      effective form of palliative care for dying patients.

PMID- 16572748
TI  - Who's caring for whom? Differing perspectives between seriously ill patients and
      their family caregivers.
AB  - Although clinicians and researchers often rely on family members 'reports of a
      wide range of dying patients' symptoms and care preferences, available data
      indicate divergences between the two. We used a national sample to analyze
      patient-caregiver pairs to explore areas of concordance and nonconcordance about
      physical symptoms, communication with physicians, caregiving needs, and future
      fears. We also assessed whether identifiable patient or caregiver characteristics
      were associated with nonconcordance. Our data were from a national, random sample
      of 988 terminally ill patients, of whom 893 had caregivers who were also
      interviewed. Frequencies and types of nonconcordance were computed for patient
      caregiver pairs. Bivariate associations between patient and caregiver reports on
      each item were tested. Logistic and conditional logistic regression analyses
      assessed multiple predictors of nonconcordance for each item. Primary diagnoses
      included cancer (51.1 percent), heart disease (17. 7 percent), chronic
      obstructive pulmonary disease (10. 7 percent), and other diseases (20.5 percent).
      The proportion of concordant reports among pairs of patients and caregivers
      ranged from 53 percent to 66 percent. Among pairs showing nonconcordant
      responses, caregivers reported higher levels of pain and disability than
      patients, lower caregiving needs, and different fears about the future. Few
      demographic or clinical predictors were associated with nonconcordance.
      Concordance between patients 'and their caregivers' responses ranged widely, and
      there were important areas of nonconcordant responses. When responses differed,
      patients were more likely to express concern about domains that might impose on
      caregivers, while caregivers were more likely to express concern about patients
      'physical suffering. Consistent sociodemographic or clinical predictors of
      nonconcordant responses were not found. These data suggest important ways that
      patient and caregiver reports of the same experience vary.

PMID- 16572749
TI  - High context illness and dying in a low context medical world.
AB  - This article provides an introduction to the field of intercultural
      communication. Miscommunication among patients, families, and clinicians often
      results when participants are contextually "out-of-synch. " High context
      communication embeds more information in the contexts within which people
      communicate and is less dependent on language. Very sick and dying patients often
      use high context communication strategies. Low context communication stresses
      explicit verbal communication and is commonly used by clinicians. When clinicians
      use low context forms of communication with patients using high context styles,
      misunderstandings frequently arise. Suggestions are given for avoiding
      miscommunication and enhancing mutual understanding.

PMID- 16572750
TI  - Building successful coalitions for promoting advance care planning.
AB  - Advance care planning (ACP) has had few successful initiatives. This qualitative
      study explores the challenges and successes of an advance care planning coalition
      in Wisconsin called Life Planning 2000 using key informant interviews (n = 24)
      and grounded theory. Major themes included: commitment (the need for leadership,
      recruitment of key members, and funding); cohesiveness (disparate groups
      collaborating toward a common purpose), and outcomes (shift in paradigm from
      signing documents to process of advanced care planning, new-found collaborative
      relationships, and educational tool development). Coalitions need to define short
      , intermediate-, and long-term goals that result in measurable outcomes and an
      evaluation process. Resources must be commensurate with goals. Strong leadership,
      paid staff adequate funding, and the collaboration of diverse groups working
      toward common goals are the basic requirements of a successful coalition.

PMID- 16572751
TI  - Antidepressant medication use in palliative care.
AB  - Depression and other mood disorders occur in approximately 25 percent of terminal
      patients. Untreated, depression and mood disorders can have a significantly
      negative impact on patients and families. Screening for depression can be done as
      easily as asking one question: "are you depressed?" A positive response to this
      question can be followed with one of the more extensive screening tools. Anxiety
      disorders can also have a negative effect on patients and their families. These
      can be identified by also using one of the validated screening tools. Use of the
      antidepressant medications for treating depression and, in some cases, anxiety
      disorders has not been well studied in hospice and palliative care. Some of the
      antidepressants can also serve as adjuvant therapy in pain management.

PMID- 16572753
TI  - Palliation in heart failure: when less and more are more.

PMID- 16572752
TI  - Are newer, more expensive pharmacotherapy options associated with superior
      symptom control compared to less costly agents used in a collaborative practice
      setting?
AB  - Innovative approaches to care may be necessary to provide the most effective
      symptom management to hospice patients. One approach is prescribing newer
      pharmacotherapy options with the potential to improve symptom management in
      hospice. Such therapies are sometimes prescribed outside of Food and Drug
      Administration indications and are typically more costly than older agents used
      for the same symptoms. Another approach is the collaborative practice (CP) care
      model, whereby clinical pharmacists are given prescriptive authority according to
      evidence-based protocols and algorithms within boundaries approved by a
      physician. The agents typically included in CP protocols are those with wide
      therapeutic indices and with substantial evidence to support their use. The
      purpose of this study was to examine both approaches to management of pain,
      insomnia, and nausea, comparing symptom scores for those patients who received
      noncollaborative drug therapies (transdermal fentanyl, zolpidem, and ondansetron)
      to those who received agents under CP (oral sustained-release opioids, temazepam,
      and prochlorperazine). The object of the study was to investigate outcomes
      associated with newer drug therapy options as compared to older agents for the
      management of pain, insomnia, and nausea. A secondary goal is to compare symptom
      outcomes for patients receiving pharmaceutical care under CP and non-CP models.
      The study design was retrospective with a cohort. A total of 50 patients were
      randomly selected for each cohort of the pain and insomnia study arms. Only 45
      patients prescribed oral ondansetron met inclusion criteria for the nausea group;
      45 patients prescribed prochlorperazine were randomly selected as the comparator
      group. Patients were compared on their degree of response to the prescribed
      therapy. Response was classified as complete, partial, no improvement from
      baseline, worsened, or unknown. A complete response was defined as the symptom
      score improving to a 0 of 10, regardless of the previous value documented. A
      partial response was defined as any improvement in score that did not result in a
      0 of 10. No improvement from baseline reflected a lack of overall change in score
      throughout the series of data points collected. A worsened response was any score
      found to be higher than the score documented at the time of dispense. The unknown
      category reflects any set of scores that had an "N/A " documented at the time of
      medication dispense or when documented for both attempts subsequent to dispensing
      the medication. A complete response was present in 14 of 50 (28 [corrected]
      percent) of the patients prescribed oral therapy [corrected] as compared with 12
      of 50 (24 [corrected] percent) of those prescribed fentanyl [corrected] (p =
      .82). Responses defined as partial, no improvement over baseline, worsened, and
      unknown were also comparable between the two cohorts. A complete response was
      seen in 26 patients prescribed temazepam (52 percent), whereas only 11 (22
      percent) of patients initially prescribed zolpidem achieved the same response (p
      = .0037). Both groups had a similar distribution of partial, no improvement over
      baseline, and worsened responses. For the nausea arm of the study, a difference
      was found in the number of complete responses, favoring prochlorperazine (22 of
      45, 48.9 percent for prochlorperazine, 12 of 45, 26.7 percent for ondansetron, p
      = .0504), as well as an increased number of worse responses seen with ondansetron
      patients (p = .0513); however, neither difference was statistically significant.
      Newer pharmacotherapy options for the management of pain, insomnia, and nausea
      were not found to be superior when compared to older agents prescribed under CP.

PMID- 16572754
TI  - Ethics roundtable. Hospice and alcoholism.

PMID- 16572755
TI  - Silent.

PMID- 16572756
TI  - A new flame retardant in the air.

PMID- 16572757
TI  - Sustainable agriculture delivers the crops.

PMID- 16572758
TI  - Canada contemplates curbs on stain repellents.

PMID- 16572759
TI  - Rain gardens stem urban storm-water flows.

PMID- 16572760
TI  - Organic vegetables are not pesticide-free.

PMID- 16572761
TI  - A vista for microbial ecology and environmental biotechnology.

PMID- 16572762
TI  - Critical analysis of the mathematical relationships and comprehensiveness of life
      cycle impact assessment approaches.
AB  - The impact assessment phase of Life Cycle Assessment (LCA) has received much
      criticism due to lack of consistency. While the ISO standards for LCA did make
      great strides in advancing the consensus in this area, ISO is not prescriptive,
      but has left much room for innovation and therefore inconsistency. To address
      this lack of consistency, there is currently an effort underway to provide a
      conceptual framework for Life Cycle Impact Assessment (LCIA) and a recommended
      practice to include a list of impact categories, category indicators, and
      underlying methodologies. This is an enormous undertaking, especially in light of
      the current fundamental lack of consensus of the basic elements to be included in
      a LCIA (e.g., impact categories, impacts, and areas of protection). ISO 14042
      requires selection of impact categories that "reflect a comprehensive set of
      environmental issues" related to the system being studied, especially for
      "comparative assertions" that involve public marketing claims. To be
      comprehensive, it is necessary to have a listing of impacts that "could" be
      included within the LCIA before entering into discussions of impacts that
      "should" be included. In addition to providing a critical analysis of existing
      and emerging impact assessment approaches, this paper will formulate a structured
      representation that allows more informed selection of approaches. The definitions
      and relationships between midpoint, endpoint, damage, and areas of protection
      will be presented in greater detail, along with the equations that are common to
      many of the approaches. Finally, a discussion of the advantages and disadvantages
      of displaying results at various stages in the environmental models will be
      presented in great detail.

PMID- 16572763
TI  - Resource-conserving agriculture increases yields in developing countries.
AB  - Despite great recent progress, hunger and poverty remain widespread and
      agriculturally driven environmental damage is widely prevalent. The idea of
      agricultural sustainability centers on the need to develop technologies and
      practices that do not have adverse effects on environmental goods and services,
      and that lead to improvements in food productivity. Here we show the extent to
      which 286 recent interventions in 57 poor countries covering 37 M ha (3% of the
      cultivated area in developing countries) have increased productivity on 12.6 M
      farms while improving the supply of critical environmental services. The average
      crop yield increase was 79% (geometric mean 64%). All crops showed water use
      efficiency gains, with the highest improvement in rainfed crops. Potential carbon
      sequestered amounted to an average of 0.35 t C ha(-1) y(-1). If a quarter of the
      total area under these farming systems adopted sustainability enhancing
      practices, we estimate global sequestration could be 0.1 Gt C y(-1). Of projects
      with pesticide data, 77% resulted in a decline in pesticide use by 71% while
      yields grew by 42%. Although it is uncertain whether these approaches can meet
      future food needs, there are grounds for cautious optimism, particularly as poor
      farm households benefit more from their adoption.

PMID- 16572764
TI  - Trends in mercury in hair of Greenlandic polar bears (Ursus maritimus) during
      1892-2001.
AB  - Mercury concentrations in hair from 397 Greenland polar bears (Ursusmaritimus)
      sampled between 1892 and 2001 were analyzed for temporal trends. In East
      Greenland the concentrations showed a significant (p < 0.0001, n = 27) increase
      of 3.1%/year in the period 1892-1973. In Northwest Greenland, a similar (p <
      0.0001, n = 69) increase of 2.1%/year was found, which continued until 1991, when
      the most recent samples were obtained. In East Greenland, a significant (p =
      0.009, n = 322) decrease of 0.8%/year was observed after 1973. Two Northwest
      Greenland samples from 1300 A.D. had a mean value of 0.52 mg/kg of dry weight,
      which can be considered as a baseline level. The Hg concentration during 1985
      1991 from Northwest Greenland (mean value of 7.45 mg/kg of dry weight) was more
      than 14-fold higher than the assumed baseline level from 1300 A.D. from the same
      region (i.e., about 93% anthropogenic). Although a decrease was found in East
      Greenland after 1973, the concentration is still ca. 11-fold higher than the
      baseline level (i.e., about 90% anthropogenic).

PMID- 16572765
TI  - Selenium speciation in kerogen from two Chinese selenium deposits: environmental
      implications.
AB  - Selenium is an essential trace element for humans, animals, and vegetation. Its
      occurrence in the environment is characterized by specific chemical and
      biochemical properties that control its elemental solubility, toxicity, and
      environmental behavior. The Laerma Se-Au deposit and Yutangba Se deposit are two
      important Se-bearing deposits found recently in China. In one of these areas
      (Yutangba), a serious environmental impact happened involving Se poisoning.
      Previous studies have shown that Se in both deposits is closely related to
      organic matter, especially kerogen fractions, but detailed relationships between
      Se and kerogen and Se chemical forms were not reported. In this study, the
      different speciation of Se is identified by transmission electron microscopy
      (TEM) and other geochemical techniques (infrared spectra (IS) and X-ray
      diffraction (XRD)) from kerogen samples extracted from ore rocks of both
      deposits. The occurrence of organically bound Se in the Laerma deposit and
      elemental Se nanograins in the Yutangba deposit is observed, indicating the
      diversity of formation mechanisms and possible chemical forms of Se in Se-rich
      rocks. The formation of elemental Se associated with organic matter is likely
      related to redox conditions, whereas organic species are related to the higher
      sulfur content of kerogen and possibly result from S-Se substitutions. This
      discovery provides new evidence with which to assess potential Se mobility during
      weathering of ore-bearing rocks. In an altered rock, the elemental Se in kerogen
      is more steadily mobilized and is potentially accumulated by vegetation, which
      may explain the sudden prevalence of Se poisoning in the Yutangba area. In
      contrast, organically bound Se seems more resistant to chemical alteration
      compared to other Se species so that its bioavailability may be very restricted.

PMID- 16572766
TI  - Determination of 14 polycyclic aromatic hydrocarbons in mainstream smoke from
      U.S. brand and non-U.S. brand cigarettes.
AB  - Tobacco smoke contains thousands of chemical compounds, including many
      carcinogenic polycyclic aromatic hydrocarbons (PAHs). To determine the
      concentration ranges of PAHs in tobacco smoke and to understand what factors
      alter their levels, we quantitatively measured 14 PAHs in mainstream smoke from a
      transnational U.S. brand (Marlboro) and from locally popular brand cigarettes
      from 14 countries. We used standardized machine smoking conditions (35-mL puff
      volume, 60-s puff interval, and 2-s puff duration), extraction of total
      particulate matter from the Cambridge filters, and gas chromatography/mass
      spectrometry detection. Deliveries of total PAHs in mainstream smoke of local
      brands were statistically significantly higher (p < 0.01) than Marlboros in seven
      countries. In four countries, Marlboro cigarettes had mainstream smoke total PAH
      levels that were statistically significantly higher (p < 0.01) than local brands.
      In the remaining three countries, the differences in PAH levels were not
      statistically significant. Under standard machine smoking conditions, PAH levels
      were negatively correlated with cigarette filter ventilation levels. We found
      that several local brands containing primarily flue-cured tobacco filler had
      relatively high mainstream smoke PAH deliveries, in agreement with findings by
      previous researchers that flue-cured tobacco typically delivers more PAHs than
      other tobacco types. We also observed that PAHs were inversely correlated with
      total carcinogenic tobacco-specific nitrosamines and nitrate content, but these
      correlations were not statistically significant at the 95% confidence interval.
      The findings suggest that tobacco blend and nitrate levels may influence PAH
      deliveries, but other factors may confound this relation.

PMID- 16572767
TI  - Temporal trends of perfluoroalkyl contaminants in polar bears (Ursus maritimus)
      from two locations in the North American Arctic, 1972-2002.
AB  - Perfluoroalkyl substances are globally distributed anthropogenic contaminants.
      Their production and use have increased dramatically from the early 1980s. While
      many recent publications have reported concentrations of perfluorooctane
      sulfonate (PFOS) and other perfluoroalkyl acids (PFAs) in biotic and abiotic
      samples, only limited work has addressed temporal trends. In this study we
      analyzed archived polar bear(Ursus maritimus) livertissue samples from two
      geographic locations in the North American Arctic, collected from 1972 to 2002.
      The eastern group, taken from the vicinity of northern Baffin Island, Canada,
      comprised 31 samples, and the western group, from the vicinity of Barrow, Alaska,
      comprised 27 samples. Samples were analyzed for perfluorocarboxylic acids (PFCAs)
      from carbon chain length C8 to C15, perfluorohexane sulfonate, PFOS, the neutral
      precursor perfluorooctane sulfonamide (PFOSA), as well as 8:2 and 10:2
      fluorotelomer acids and their alpha,beta unsaturated acid counterparts.
      Concentrations of PFOS and PFCAs with carbon chain lengths from C9 to C11 showed
      an exponential increase between 1972 and 2002 at both locations. Doubling times
      ranged from 3.6 +/- 0.9 years for perfluorononanoic acid in the eastern group to
      13.1 +/- 4.0 years for PFOS in the western group. PFOSA showed decreasing
      concentrations over time at both locations, while the remaining PFAs showed no
      significant trends or were not detected in any sample. The doubling time for PFOS
      was similar to the doubling time of production of perfluoroctylsulfonyl-fluoride
      based products during the 1990s.

PMID- 16572768
TI  - Trace metal concentrations and water solubility in size-fractionated atmospheric
      particles and influence of road traffic.
AB  - The abundance and the behavior of metals (Al, Ti, Mn, Fe, Co, Ni, Cu, Zn, Se, Ag,
      Cd, Sn, Ba, Pt, Hg, and Pb) and ions (Na+ K+ Mg2+ Ca2+, NH4+, Cl-, NO3-, SO4(2-),
      PO4(3-), and oxalate) in size-fractionated atmospheric particulate matter (PM)
      were studied in the U. K. and Ireland at four observation sites simulating
      extreme degrees of vehicular-traffic influence in the environment. Trace metals
      in urban PM showed distinct types of size-fractionated behavior depending on the
      particle sources from which they originate. In coarse PM (1.5 < Dp < 3.0 microm)
      the concentrations of copper, barium, and iron correlated closely across over 2
      orders of magnitude in urban air, which is seen as evidence that major portions
      of transition metals (Cu, Ba, Fe, and Mn) are released through abrasive vehicular
      emissions, particularly the wear of brake linings. Further results are strongly
      indicative of a decoupling of coarse iron and calcium, the former arising
      predominantly from vehicles, the latter from soil resuspension. In fine PM (Dp <
      0.5 microm), several combustion and secondary sources of particulates were
      identified, but these were much less unique in terms of elemental fingerprints.
      An analysis of the water solubility of trace metals yielded that solubility
      varies considerably with element and, to a lesser extent, with particle size.
      Notable differences were found to the elemental water solubilities determined in
      previous work, partially explained by differences in extraction procedures.

PMID- 16572769
TI  - Long-term natural attenuation of carbon and nitrogen within a groundwater plume
      after removal of the treated wastewater source.
AB  - Disposal of treated wastewater for more than 60 years onto infiltration beds on
      Cape Cod, Massachusetts produced a groundwater contaminant plume greater than 6
      km long in a surficial sand and gravel aquifer. In December 1995 the wastewater
      disposal ceased. A long-term, continuous study was conducted to characterize the
      post-cessation attenuation of the plume from the source to 0.6 km downgradient.
      Concentrations and total pools of mobile constituents, such as boron and nitrate,
      steadily decreased within 1-4 years along the transect. Dissolved organic carbon
      loads also decreased, but to a lesser extent, particularly downgradient of the
      infiltration beds. After 4 years, concentrations and pools of carbon and nitrogen
      in groundwater were relatively constant with time and distance, but substantially
      elevated above background. The contaminant plume core remained anoxic for the
      entire 10-year study period; temporal patterns of integrated oxygen deficit
      decreased slowly at all sites. In 2004, substantial amounts of total dissolved
      carbon (7 mol C m(-2)) and fixed (dissolved plus sorbed) inorganic nitrogen (0.5
      mol N m(-2)) were still present in a 28-m vertical interval at the disposal site.
      Sorbed constituents have contributed substantially to the dissolved carbon and
      nitrogen pools and are responsible for the long-term persistence of the
      contaminant plume. Natural aquifer restoration at the discharge location will
      take at least several decades, even though groundwater flow rates and the
      potential for contaminant flushing are relatively high.

PMID- 16572770
TI  - 2004 National Atrazine Occurrence Monitoring Program using the Abraxis ELISA
      method.
AB  - The goal of this project was to gain a better understanding of atrazine
      occurrence in the United States by surveying drinking water utilities' sources
      and finished water for atrazine on a weekly basis for seven months. Atrazine is a
      contaminant of interest because the United States Environmental Protection Agency
      (USEPA) has found short-term atrazine exposure above the drinking water maximum
      contaminant level (MCL) to potentially cause heart, lung, and kidney congestion,
      low blood pressure, muscle spasms, weight loss, and damage to the adrenal glands.
      Long-term exposure to atrazine concentrations above the drinking water MCL has
      been linked to weight loss, cardiovascular damage, retinal and muscle
      degeneration, and cancer. This survey effort improved upon previously conducted
      atrazine surveys through intensive, high frequency sampling (participating plants
      sampled their raw and finished water on a weekly basis for approximately seven
      months). Such an intensive effort allowed the authors to gain a better
      understanding of short-term atrazine occurrence and its variability in drinking
      water sources. This information can benefit the drinking water industry by
      facilitating (1) better atrazine occurrence management (i.e., awareness when
      plants may be more susceptible to atrazine), (2) more efficient atrazine control
      (e.g., effective treatment alternatives and more effective response to atrazine
      occurrence), and (3) treatment cost reduction (e.g., efficient atrazine control
      can result in substantial cost savings). Forty-seven drinking watertreatment
      plants located primarily in the Midwestern United States participated in the
      survey and sampled their raw and finished water on a weekly basis from March
      through October. Samples were analyzed using the Abraxis enzyme-linked
      immunosorbent assay (ELISA) test kit. Confirmation samples for quality
      assurance/quality control (QA/QC) purposes were analyzed using solid-phase
      extraction (SPE) followed by gas chromatography mass spectrophotometry (GC/MS).
      Several important conclusions can be drawn from this study including (1) surface
      waters were confirmed to be more vulnerable to atrazine contamination than
      groundwater sources, (2) peak atrazine concentrations corresponded well to
      precipitation/runoff events, and (3) atrazine occurrence tended to be uniform
      geographically when compared by river drainage basins. In addition, this project
      confirmed that the Abraxis atrazine ELISA test kit tended to have a positive bias
      (i.e., the measured ELISA concentration was higher than the actual concentration)
      in most measured samples. Finished samples tended to have more of a positive bias
      than raw water samples. Therefore, this bias may limit the effectiveness for
      ELISA for regulatory monitoring. There are many other applications for ELISA,
      however, including frequent monitoring for early detections of atrazine
      concentration changes that might trigger conventional analysis by GC/MS or be
      used for activated carbon dosing or other treatment operating controls.

PMID- 16572771
TI  - Residual indoor contamination from world trade center rubble fires as indicated
      by polycyclic aromatic hydrocarbon profiles.
AB  - The catastrophic destruction of the World Trade Center (WTC) on Sept. 11, 2001
      (9/11) created an immense dust cloud followed by fires that emitted smoke and
      soot into the air of New York City (NYC) well into December. Outdoor pollutant
      levels in lower Manhattan returned to urban background levels after about 200
      days as the fires were put out and the debris cleanup was completed. However,
      particulate matter (PM) from the original collapse and fires also penetrated into
      commercial and residential buildings. This has created public concern because WTC
      dust is thought to cause adverse pulmonary symptoms including "WTC cough" and
      reduced lung capacity. Additionally, some recent studies have suggested a
      possible link between exposure to WTC contamination and other adverse health
      effects. Distinguishing between normal urban pollutant infiltration and residual
      WTC dust remaining in interior spaces is difficult; efforts are underway to
      develop such discriminator methods. Some progress has been made in identifying
      WTC dust by the content of fibers believed to be associated with the initial
      building collapse. There are also contaminants created by the fires that burned
      for 100 days in the debris piles of the building rubble. Using WTC ambient air
      samples, we have developed indicators for fire related PM based on the relative
      amounts of specific particle bound polycyclic aromatic hydrocarbons (PAHs) and
      the mass fraction of PAHs per mass of PM. These two parameters are combined, and
      we show a graphical method for discriminating between fire sources and urban
      particulate sources as applied to samples of settled dusts. We found that our
      PAHs based discriminator method can distinguish fire source contributions to WTC
      related particulate matter and dusts. Other major building fires or large open
      burn events could have similar PAHs characteristics. We found that random samples
      collected approximately 3.5 years after the WTC event from occupied indoor spaces
      (primarily residential) in the New York area are not statistically
      distinguishable from contemporary city background.

PMID- 16572772
TI  - Temporal trends of polychlorinated biphenyls in precipitation and air at chicago.
AB  - Polychlorinated biphenyl (PCB) concentrations in precipitation (1997-2003) and in
      the atmospheric gas phase (1996-2003) collected in Chicago, IL, are reported.
      These data were obtained as part of the Integrated Atmospheric Deposition
      Network. For comparison, PCB concentrations at a remote site, Sleeping Bear Dunes
      on the northeastern shore of Lake Michigan, are also reported. Much higher PCB
      concentrations in both precipitation (7.1 +/- 0.9 ng/L) and the gas phase (1.4 +/
      0.1 ng/m3) at Chicago compared to Sleeping Bear Dunes (1.1 +/- 0.1 ng/L and 0.1
      +/- 0.08 ng/m3, respectively) indicate that Chicago is a source of PCBs to the
      Great Lakes. A long-term decreasing trend of PCB concentrations in precipitation
      was observed at Chicago with a half-life of 6.8 +/- 3.1 years. The corresponding
      half-life for PCB concentrations in the gas phase was 7.7 +/- 1.1 years. The
      significant long-term decrease of PCB concentrations in precipitation and the gas
      phase in Chicago suggests that regulatory efforts are working, at least in this
      city.

PMID- 16572773
TI  - Dechlorane plus, a chlorinated flame retardant, in the Great Lakes.
AB  - A highly chlorinated flame retardant, Dechlorane Plus (DP), was detected and
      identified in ambient air, fish, and sediment samples from the Great Lakes
      region. The identity of this compound was confirmed by comparing its gas
      chromatographic retention times and mass spectra with those of authentic
      material. This compound exists as two gas chromatographically separable
      stereoisomers (syn and anti), the structures of which were characterized by one-
      and two-dimensional proton nuclear magnetic resonance. DP was detected in most
      air samples, even at remote sites. The atmospheric DP concentrations were higher
      at the eastern Great Lakes sites (Sturgeon Point, NY, and Cleveland, OH) than
      those at the western Great Lakes sites (Eagle Harbor, MI, Chicago, IL, and
      Sleeping Bear Dunes, MI). Atthe Sturgeon Point site, DP concentrations once
      reached 490 pg/m3. DP atmospheric concentrations were comparable to those of BDE
      209 at the eastern Great Lakes sites. DP was also found in sediment cores from
      Lakes Michigan and Erie. The peak DP concentrations were comparable to BDE-209
      concentrations in the sediment core from Lake Erie butwere about 30 times lower
      than BDE-209 concentrations in the core from Lake Michigan. In the sediment
      cores, the DP concentrations peaked around 1975-1980, and the surficial
      concentrations were 10-80% of peak concentrations. Higher DP concentrations in
      air samples from Sturgeon Point, NY, and in the sediment core from Lake Erie
      suggest that DP's manufacturing facility in Niagara Falls, NY, may be a source.
      DP was also detected in archived fish (walleye) from Lake Erie, suggesting that
      this compound is, at least partially, bioavailable.

PMID- 16572774
TI  - Concentration levels, compositional profiles, and gas-particle partitioning of
      polybrominated diphenyl ethers in the atmosphere of an urban city in South China.
AB  - Air samples were collected in June of 2004 from four sites in the city of
      Guangzhou, a typical urban center in South China, to determine the levels,
      compositional profiles, and gas-particle distribution of 11 polybrominated
      diphenyl ether (PBDE) congeners (BDE-28, -47, -66, -100, -99, -85, -154, -153, 
      138, -183, and -209). The arithmetic mean atmospheric concentrations of
      sigmaPBDEs (sum of all target PBDE congeners except for BDE-209) in samples from
      the urban and city background sites were comparable to or slightly higher than
      those from other places around the world. The arithmetic mean atmospheric
      concentrations of BDE-209, however, were higherthan those in North America and
      Europe, and similar to the values from Japan. Congener compositions were
      dominated by BDE-209 in all (>70%) but an industrial site, with an average
      abundance of 48% for BDE-209. The PBDE patterns were generally similar to that in
      the technical penta-BDE mixture, Bromkal 70-5DE. Partitioning of PBDEs between
      the gas and particle phases (Kp) was well correlated with the subcooled liquid
      vapor pressure (PLO) for all of the samples, but the relationship differed
      between samples from different sites. The measured fractions of PBDEs in the
      particulate phase were compared to the predictions from the Junge-Pankow
      adsorption and KOA-based absorption models. The results indicated that the KOA
      based model worked better than the Junge-Pankow model that tended to overestimate
      the particulate fractions for most PBDE congeners.

PMID- 16572775
TI  - Strong sorption of native PAHs to pyrogenic and unburned carbonaceous geosorbents
      in sediments.
AB  - It has recently been shown that the presence of carbonaceous geosorbents (CG,
      including black carbon (BC), unburned coal, and kerogen) can cause strong
      sorption of polycyclic aromatic hydrocarbons (PAHs) in sediments. We studied
      sorption of native PAHs in four Norwegian harbor sediments of which high
      fractions (21-56%) of the total organic carbon (TOC) consisted of CG carbon
      (CGC), as shown by organic petrography. PAH sorption coefficients were 1-2 orders
      of magnitude above predictions based on amorphous organic carbon partitioning
      alone. In recent studies, such strong sorption was attributed solely to BC
      sorption under the implicit assumption that sorption is linear for coal and
      kerogen. The most important result of the present study is that total sorption is
      better explained by considering all three nonlinearly sorbing CGC materials than
      by only considering BC. In addition, it was evaluated whether activated carbon
      (AC) amendments could be effective in reducing the freely dissolved pore-water
      concentrations (CW) and thus the environmental risks of the PAHs in such strongly
      sorbing sediments. The results indicated that an addition of 2 weight % AC
      reduced the Cw by factors of 21-153 for the four sediments (average values for
      all PAHs). Itwas shown that phenanthrene sorption to AC was, on average, reduced
      by a factor of 6 in sediment-AC mixtures compared to pure AC.

PMID- 16572776
TI  - Biogeochemical cycling of methylmercury in lakes and tundra watersheds of Arctic
      Alaska.
AB  - The fate of atmospherically deposited and environmentally active Hg is uncertain
      in the Arctic, and of greatest toxicological concern is the transformation to
      monometh-ylmercury (MMHg). Lake/watershed mass balances were developed to examine
      MMHg cycling in four northern Alaska lakes near the ecological research station
      at Toolik Lake (68 degrees 38' N, 149 degrees 36' W). Primary features of the
      cycle are watershed runoff, sedimentary production and mobilization, burial, and
      photodecomposition in the water column. The principal source of MMHg is in situ
      benthic production with 80-91% of total inputs provided by diffusion from
      sediments. The production and contribution of MMHg from tundra watersheds is
      modest. Photodecomposition, though confined to a short ice-free season, provides
      the primary control for MMHg (66-88% of total inputs) and greatly attenuates
      bioaccumulation. Solid-phase MMHg and gross potential rates of Hg methylation,
      assayed with an isotopic tracer, vary positively with the level of inorganic Hg
      in filtered pore water, indicating that MMHg production is Hg-limited in these
      lakes. Moreover, sediment-waterfluxes of MMHg (i.e., net production at steady
      state) are related to sediment Hg loadings from the atmosphere. These results
      suggest that loadings of Hg derived from atmospheric deposition are a major
      factor affecting MMHg cycling in arctic ecosystems. However, environmental
      changes associated with warming of the Arctic (e.g., increased weathering,
      temperature, productivity, and organic loadings) may enhance MMHg bioaccumulation
      by stimulating Hg methylation and inhibiting photodecomposition.

PMID- 16572777
TI  - Photodecomposition of methylmercury in an Arctic Alaskan lake.
AB  - Sunlight-induced decomposition of monomethylmercury (MMHg) reduces its
      availability for accumulation in aquatic food webs. We examined MMHg degradation
      in epilimnetic waters of Toolik Lake (68 degrees 38' N, 149 degrees 36' W) in
      arctic Alaska, a region illuminated by sunlight almost continuously during the
      summer. MMHg decomposition in surface water of Toolik Lake is exclusively abiotic
      and mediated by sunlight; comparable rates of MMHg decomposition were observed in
      filter-sterilized and unfiltered surface waters incubated under in situ sunlight
      and temperature conditions, and no MMHg was degraded in unfiltered aliquots
      incubated in the dark. Rates of photodecomposition are first order with respect
      to both MMHg concentration and the intensity of photosynthetically active
      radiation (PAR), except at the lake surface where rates of photochemical
      degradation are enhanced relative to PAR intensity and may be attributed to an
      additional influence of ultraviolet light. The estimated annual loss of MMHg to
      photodecomposition in Toolik Lake, though limited to a 100-d ice-free season,
      accounts for about 80% of the MMHg mobilized annually from in situ sedimentary
      production, the primary source in Toolik Lake. These results suggest that greater
      light attenuation in lacustrine surface waters, a potential result of increased
      loadings of dissolved organic matter due to continued warming in the Arctic, may
      result in less photodecomposition and subsequently greater availability of MMHg
      for bioaccumulation.

PMID- 16572778
TI  - Acid-volatile sulfide oxidation in coastal flood plain drains: iron-sulfur
      cycling and effects on water quality.
AB  - The effect of acid-volatile sulfide (AVS) oxidation on Fe-S cycling and water
      quality in coastal flood plain drains from acid-sulfate soil landscapes was
      examined using natural sediments and synthetic iron monosulfide. Oxidation of AVS
      occurred rapidly (half-time < or = 1 h) and produced elemental sulfur (S8(0)(s))
      and iron oxyhydroxide (FeOOH(s)). The initial rapid AVS oxidation process
      occurred without significant acidification or changes to the aqueous-phase
      composition. Severe acidification (pH < 4) occurred only once S8(0)(s) began to
      oxidize to SO4 (within 2-3 days of the initial AVS oxidation). Our results
      demonstrate, for the first time with natural sediments, a significant pH-buffered
      (near-neutral) AVS oxidation step with the trigger to acidification being the
      oxidation of S8(0)(s). Acidification resulted in the pH-dependent release of
      large amounts of Al, Mn, Ni, and Zn even though the sediment metal content was
      low.

PMID- 16572779
TI  - CCN activation of pure and coated carbon black particles.
AB  - The CCN (cloud condensation nucleus) activation of pure and coated carbon black
      particles was investigated using the University of Vienna cloud condensation
      nuclei counter (Giebl, H.; Berner, A.; Reischl, G.; Puxbaum, H.; Kasper-Giebl,
      A.; Hitzenberger, R. J. Aerosol Sci. 2002, 33, 1623-1634). The particles were
      produced by nebulizing an aqueous suspension of carbon black in a Collison
      atomizer. The activation of pure carbon black particles was found to require
      higher supersaturations than predicted by calculations representing the particles
      as insoluble, wettable spheres with mobility equivalent diameter. To test whether
      this effect is an artifact due to heating of the light-absorbing carbon black
      particles in the laser beam, experiments at different laser powers were
      conducted. No systematic dependence of the activation of pure carbon black
      particles on laser power was observed. The observations could be modeled using
      spherical particles and an effective contact angle of 4-6 degrees of water at
      their surface. The addition of a small amount of NaCl to the carbon black
      particles (by adding 5% by mass NaCl to the carbon black suspension) greatly
      enhanced their CCN efficiency. The measured CCN efficiencies were consistent with
      Kohler theory for particles consisting of insoluble and hygroscopic material.
      However, coating the carbon black particles with hexadecanol (a typical film
      forming compound with one hydrophobic and one hydrophilic end) efficiently
      suppressed the CCN activation of the carbon black particles.

PMID- 16572780
TI  - Diesel engine exhaust emission: oxidative behavior and microstructure of black
      smoke soot particulate.
AB  - Soot particulate collected from a Euro III heavy duty diesel engine run under
      black smoke conditions was investigated using thermogravimetry, transmission
      electron microscopy, electron energy loss spectroscopy, and X-ray photoelectron
      spectroscopy. The characterization results are compared with those of commercial
      carbon black. The onset temperature toward oxidation of the diesel engine soot in
      5% O2 is 150 degrees C lower than that for carbon black. The burn out temperature
      for the diesel engine soot is 60 degrees C lower than that of the carbon black.
      The soot primary particles exhibit a core-shell structure. The shell of the soot
      particles consists of homogeneously stacked basic structure units. The commercial
      carbon lamp black is more graphitized than the diesel engine soot, whereas the
      diesel engine soot contains more carbon in aromatic nature than the carbon black
      and is highly surface-functionalized. Our findings reveal that technical carbon
      black is not a suitable model for the chemistry of the diesel engine soot.

PMID- 16572781
TI  - Buffering of alkaline steel slag leachate across a natural wetland.
AB  - Buffering of high-pH (>12) steel slag leachate is documented across a small,
      natural calcareous wetland. The alkaline leachate is supersaturated with respect
      to calcite upstream of the wetland (Sl(calcite) values +2.3) and becomes less
      saturated with progress across the wetland, to Sl(calcite) values of +0.27 at the
      wetland outlet. Reduction in pH across the wetland (to around pH 8 at the wetland
      outlet) was observed to be more pronounced over summer months, possibly due to
      increased microbial activity, possibly further assisted by greater flow baffling
      by emergent vegetation. Calculated calcite precipitation rates downstream of the
      leachate source, estimated from hydrochemical data, flow, and surface area, were
      on the order of 0.4-15 g m(-2) day(-1), while direct measurements (using immersed
      limestone blocks) showed calcite precipitation values in the range 3-10 g m(-2)
      day(-1). Precipitation rate was highest in the pH range where the carbonate ion
      is a dominant constituent of sample alkalinity (pH 9.5-11) and at the locations
      where wetland biota became established downstream of the leachate emergence.
      These data provide valuable insights into the potential for using constructed
      wetlands for the passive treatment of high pH steel slag leachates.

PMID- 16572782
TI  - Adsorption of uranyl on gibbsite: A time-resolved laser-induced fluorescence
      spectroscopy study.
AB  - Uranyl adsorbed on gibbsite at pH 4.0-8.0 and ionic strengths (ISs) 0.001-0.4 M
      (NaClO4) in the absence of carbonate was studied using time-resolved laser
      induced fluorescence spectroscopy (TRLIFS) under cryogenic conditions. TRLIFS
      data showed the presence of several distinct emission components. Their
      contributions were determined using the evolving factor analysis approach. Four
      components denoted as species A, B, C, and D were discerned. Each of them was
      characterized by a characteristic response to pH and IS changes and also by a
      unique combination of the values of the fundamental transition energy E0,0,
      vibronic spacing deltaE, and half-width of the vibronic lines deltaW. Species A
      and B were major contributors to the overall emission. They were mainly affected
      by the pH and predominated below and above pH 5.0, respectively. In contrast with
      that, the contribution of species C was noticeable only at IS = 0.001 M, while it
      was suppressed or absent at high IS values. It was concluded that species A and B
      are likely to correspond to inner-sphere surface aluminol complexes =AlO-(UO2)+
      and =AlO-(UO2)OH degrees, while species C was hypothesized to correspond to
      electrostatically bound uranyl complexes (predominantly [UO2(OH)3]-).

PMID- 16572783
TI  - Using size fractionation and Pb isotopes to study Pb transport in the waters of
      an organic-rich upland catchment.
AB  - Processes controlling Pb release from a small organic-rich upland catchment in
      northeast Scotland were investigated via measurement of Pb concentrations and
      206Pb/207Pb ratios in rainwater, throughflow, surface flow, and receiving
      streamwaters under storm and baseflow conditions. For this catchment, the output
      of Pb via streams was only 2.0 +/- 1.2 kg year(-1) (11.4 +/- 6.8 g ha(-1) year(
      1)), much lower than the input of 7.5 +/- 2.0 kg year(-1) (42.6 +/- 11.4 g ha(-1)
      year(-1)), and so the catchment is still a sink for anthropogenic Pb. Most (68
      87%) of the output, however, occurred under storm conditions. Size fractionation
      revealed that 50-60% was in large particulate form (>25 microm) with a 206Pb/
      207Pb ratio of approximately 1.16, similar to that of the surface soils. Some 30
      40% of the storm Pb output was associated with dissolved organic matter in the
      <0.45 microm fraction and had a lower 206Pb/207Pb ratio of approximately 1.14,
      close to the value obtained for near-surface throughflow. Future extreme weather
      conditions such as prolonged dry or wet periods will increase transport of Pb to
      receiving waters. Although particulate forms could then rapidly be removed under
      low flow conditions, Pb associated with dissolved organic matter will persist
      longer in aquatic systems and may also be more bioavailable.

PMID- 16572784
TI  - Adsorption mechanism of arsenic on nanocrystalline titanium dioxide.
AB  - Arsenate [As(V)] and arsenite [As(III)] interactions at the solid-water interface
      of nanocrystalline TiO2 were investigated using electrophoretic mobility (EM)
      measurements, Fourier transform infrared (FTIR) spectroscopy, extended X-ray
      absorption fine structure (EXAFS) spectroscopy, and surface complexation
      modeling. The adsorption of As(V) and As(III) decreased the point of zero charge
      of TiO2 from 5.8 to 5.2, suggesting the formation of negatively charged inner
      sphere surface complexes for both arsenic species. The EXAFS analyses indicate
      that both As(V) and As(III) form bidentate binuclear surface complexes as
      evidenced by an average Ti-As(V) bond distance of 3.30 A and Ti-As(III) bond
      distance of 3.35 A. The FTIR bands caused by vibrations of the adsorbed arsenic
      species remained at the same energy levels at different pH values. Consequently,
      the surface complexes on TiO2 maintained the same nonprotonated speciation at pH
      values from 5 to 10, and the dominant surface species were (TiO)2AsO2- and
      (TiO)2AsO- for As(V) and As(III), respectively. The surface configurations
      constrained with the spectroscopic results were formulated in the diffuse layer
      model to describe the adsorption behavior of As in the pH range between 4 and 12.
      The study suggests that TiO2 is an effective adsorbent for As removal due to its
      high surface area and the presence of high affinity surface hydroxyl groups.

PMID- 16572785
TI  - Formation of dioxins from combustion micropollutants over MSWI fly ash.
AB  - Formation of polychlorinated dibenzofurans and dibenzo-p-dioxins (PCDD/Fs) from a
      model mixture of products of incomplete combustion (PICs) representative of
      municipal solid waste incineration (MSWI) flue gases, over a fixed bed of MSWI
      fly ash has been investigated. For comparison, a single model compound
      (chlorobenzene) was also briefly studied. A newly developed lab-scale system
      enabled the application of (very) low and stable concentrations of organic
      substances--of 10(-6) M or less-to approach realistic conditions. Samples taken
      at several time intervals allowed the observation of changes in rates and
      patterns due to depletion of the carbon in fly ash. The model flue gas
      continuously produced PCDDs and PCDFs after the de novo reaction had ceased to
      occur. Dioxin output levels are comparable to those of "old" MSW incinerators.
      Replacing the PIC trace constituent phenol by its fully 13C-labeled analogue led
      to, e.g., PCDD with one labeled ring as prominent product, meaning that the
      formation is about first order in phenol, contrary to earlier assumptions. The
      meaning of the results for the formation of dioxins in the MSWI boiler is
      discussed.

PMID- 16572786
TI  - A predictive model to correlate fuel specifications with on-road vehicles
      emissions in Mexico.
AB  - Mexico is currently in the process of implementing its third air management
      program, which includes control measures targeting emissions reductions from
      mobile, point, and area sources. Achieving the program goals will require changes
      in the composition and in physical properties of gasoline and implementing an
      emissions reduction schedule. For that purpose a study was undertaken to support
      understanding of the effect of gasoline fuel parameters on exhaust emissions.
      Specifically, the relative impacts of Reid vapor pressure, distillation
      parameters, oxygen, sulfur, olefins, and aromatic contents on the exhaust
      emissions of in-use vehicles of the metropolitan area of Mexico City were
      investigated. The results were used to develop a model to predict CO, nitrogen
      oxides, total hydrocarbons, and toxic emissions such as benzene, 1,3-butadiene,
      formaldehyde, and acetaldehyde. Also a statistical model that predicts
      evaporative emissions was built. Results of the present model are compared with
      those obtained using the complex model of the United States Environmental
      Protection Agency.

PMID- 16572787
TI  - Chemical-equilibrium-based model for describing the strength of sludge: taking
      hydrogen-producing sludge as an example.
AB  - A new model, based on chemical equilibrium theory, was established to evaluate
      the strength of sludges in biological wastewater treatment systems. The
      effectiveness of this model was demonstrated by the experimental results with an
      anaerobic hydrogen-producing sludge. The equilibrium dispersed mass concentration
      of the primary particles in the sludge solution was found to nonlinearly increase
      with the solid content and shear intensity, and could be well described by the
      model. The Gibbs free energy of adhesion (deltaG degrees) under shear could also
      be calculated using this model. The equilibrium constant K degrees and deltaG
      degrees/ RTat a shear intensity of 800 1/s were estimated to be 6.54 +/- 0.12 and
      1.88 +/- 0.02, respectively. The two parameters could be used to evaluate the
      strength of the hydrogen-producing sludge. In addition, the effectiveness of the
      established model was also confirmed by the results with activated sludge in the
      literature.

PMID- 16572788
TI  - Modeling ozone and aerosol formation and transport in the pacific northwest with
      the community Multi-Scale Air Quality (CMAQ) modeling system.
AB  - The Community Multi-Scale Air Quality (CMAQ) modeling system was used to
      investigate ozone and aerosol concentrations in the Pacific Northwest (PNW)
      during hot summertime conditions during July 1-15, 1996. Two emission inventories
      (El) were developed: emissions for the first El were based upon the National
      Emission Trend 1996 (NET96) database and the BEIS2 biogenic emission model, and
      emissions for the second El were developed through a "bottom up" approach that
      included biogenic emissions obtained from the GLOBEIS model. The two simulations
      showed that elevated PM2.5 concentrations occurred near and downwind of the
      Interstate-5 corridor along the foothills of the Cascade Mountains and in
      forested areas of central Idaho. The relative contributions of organic and
      inorganic aerosols varied by region, but generally organic aerosols constituted
      the largest fraction of PM2.5. In wilderness areas near the 1-5 corridor, organic
      carbon from anthropogenic sources contributed approximately 50% of the total
      organic carbon with the remainder from biogenic precursors, while in wilderness
      areas in Idaho, biogenic organic carbon accounted for 80% of the total organic
      aerosol. Regional analysis of the secondary organic aerosol formation in the
      Columbia River Gorge, Central Idaho, and the Olympics/Puget Sound showed that the
      production rate of secondary organic carbon depends on local terpene
      concentrations and the local oxidizing capacity of the atmosphere, which was
      strongly influenced by anthropogenic emissions. Comparison with observations from
      12 IMPROVE sites and 21 ozone monitoring sites showed that results from the two
      El simulations generally bracketed the average observed PM parameters and that
      errors calculated for the model results were within acceptable bounds. Analysis
      across all statistical parameters indicated that the NW-AIRQUEST El solution
      performed better at predicting PM2.5, PM1, and beta(ext) even though organic
      carbon PM was over-predicted, and the NET96 El solution performed better with
      regard to the inorganic aerosols. For the NW-AIRQUEST El solution, the normalized
      bias was 30% and the normalized absolute error was 49% for PM2.5 mass. The NW
      AIRQUEST solution slightly overestimated peak hourly ozone downwind of urban
      areas, while the NET96 solution slightly underestimated peak values, and both
      solutions over-predicted average 03 concentrations across the domain by
      approximately 6 ppb.

PMID- 16572789
TI  - Confocal microprobe Raman imaging of urban tropospheric aerosol particles.
AB  - Particulate matter with aerodynamic diameters of < 1, 1-2.5, and 2.5-10 microm
      were collected during two seasons in two urban zones situated northeast and
      southwest, respectively, of a lead/zinc smelter located in a former mining region
      of northern France. We demonstrate the effectiveness of the combined use of
      computer-controlled Raman mapping and multivariate curve resolution (MCR) of the
      Raman images to determine heterogeneous chemistry at the level of aerosol
      particle. The resulting molecular images of major species were found to be in
      accurate agreement with elemental images obtained by WDS X-ray-mapping.
      Environmental SEM was very useful to localize spare metal-rich particles before
      Raman mapping. Some spare particles containing pyromorphite (Pb5(PO4)3OH) and
      franklinite (ZnxFe3-xO4) mixed with mineral dust were detected at the northeast
      (NE) sampling site, when the wind was blowing from the west (W) sector. These
      particles were probably suspended in the troposphere by the action of wind or by
      mechanical disturbance of polluted top soils. The most abundantly encountered
      particles in the 10-2.5 and 2.5-1 microm fractions were found to be aggregates of
      NaCl, CaCO3, CaSO4 x 2H2O, CaMg(CO3)2, SiO2, feldspar, clay minerals, alpha
      Fe2O3, NaNO3, and Ca(NO3)2 x 4H20. Black carbon and (NH4)2SO4 particles were
      observed predominantly in the finest fraction. It was not rare to detect Pb and
      Zn-rich particles in the 10-2.5 and 2.5-1 microm fractions collected at the
      southwest (SW) sampling site, when the wind was blowing from the NE sector. Most
      of these mixed particles probably result from the aggregation between PbSO4, PbO
      x PbSO4, and ZnS particles emitted by the smelters and hydroscopic mineral dust
      during transport in the troposphere.

PMID- 16572790
TI  - Freely dissolved concentrations of PAHs in soil pore water: measurements via
      solid-phase extraction and consequences for soil tests.
AB  - Freely dissolved pore water concentrations are difficult to assess in complex
      matrixes such as soils or sediments. In this study, a negligible-depletion
      partitioning-based sampling technique was applied to measure freely dissolved
      pore water concentrations. A poly(dimethylsiloxane) (PDMS)-coated glass fiber was
      exposed to a slurry of a soil spiked with several PAHs at concentrations ranging
      from 2 to 2000 mg/kg. PAH-concentrations in the PDMS coating increased linearly
      with the total soil concentration until a certain maximum was reached. Freely
      dissolved pore water concentrations were calculated using PDMS-water partition
      coefficients, and the calculated maximum pore water concentrations corresponded
      with the aqueous solubility of the tested compounds. Furthermore, the sampling
      technique is very sensitive because it can detect freely dissolved pore water
      concentrations in the ng/L range for the tested PAHs. Freely dissolved pore water
      concentrations are an important parameter for the exposure of organisms in soil.
      Saturation of the pore water with increasing soil concentrations should therefore
      be considered in soil toxicity testing. Sorption coefficients that were
      calculated from freely dissolved concentrations were slightly higher than
      estimates based on octanol-water partition coefficients. These differences are
      discussed in relation to the effects of dissolved organic matter in soil pore
      water on the determination of sorption coefficients.

PMID- 16572791
TI  - Influence of diesel fuel sulfur on nanoparticle emissions from city buses.
AB  - Particle emissions from twelve buses, operating alternately on low sulfur (LS;
      500 ppm) and ultralow sulfur (ULS; 50 ppm) diesel fuel, were monitored. The buses
      were 1-19 years old and had no after-treatment devices fitted. Measurements were
      carried out at four steady-state operational modes on a chassis dynamometer using
      a mini dilution tunnel (PM mass measurement) and a Dekati ejector diluter as a
      secondary diluter (SMPS particle number). The mean particle number emission rate
      (s(-1)) of the buses, in the size range 8-400 nm, using ULS diesel was 31% to 59%
      lower than the rate using LS diesel in all four modes. The fractional reduction
      was highest in the newest buses and decreased with mileage upto about 500,000 km,
      after which no further decrease was apparent. However, the mean total suspended
      particle (TSP) mass emission rate did not show a systematic difference between
      the two fuel types. When the fuel was changed from LS to ULS diesel, the
      reduction in particle number was mainly in the nanoparticle size range. Over all
      operational modes, 58% of the particles were smaller than 50 nm with LS fuel as
      opposed to just 45% with ULS fuel, suggesting that sulfur in diesel fuel was
      playing a major role in the formation of nanoparticles. The greatest influence of
      the fuel sulfur content was observed at the highest engine load, where 74% of the
      particles were smaller than 50 nm with LS diesel compared to 43% with ULS diesel.

PMID- 16572792
TI  - Exploring molecular sieve capabilities of activated carbon fibers to reduce the
      impact of NOM preloading on trichloroethylene adsorption.
AB  - Adsorption of trichloroethylene (TCE) by two activated carbon fibers (ACFs) and
      two granular activated carbons (GACs) preloaded with hydrophobic and transphilic
      fractions of natural organic matter (NOM) was examined. ACF10, the most
      microporous activated carbon used in this study, had over 90% of its pore volume
      in pores smaller than 10 A. It also had the highest volume in pores 5-8 A, which
      is the optimum pore size region for TCE adsorption, among the four activated
      carbons. Adsorption of NOM fractions by ACF10 was, in general, negligible.
      Therefore, ACF10, functioning as a molecular sieve during preloading, exhibited
      the least NOM uptake for each fraction, and subsequently the highest TCE
      adsorption. The other three sorbents had wider pore size distributions, including
      high volumes in pores larger than 10 A, where NOM molecules can adsorb. As a
      result, they showed a higher degree of uptake for all NOM fractions, and
      subsequently lower adsorption capacities for TCE, as compared to ACF10. The
      results obtained in this study showed that understanding the interplay between
      the optimum pore size region for the adsorption of target synthetic organic
      contaminant (SOC) and the pore size region for the adsorption of NOM molecules is
      important for controlling NOM-SOC competitions. Experiments with different NOM
      fractions indicated that the degree of NOM loading is important in terms of
      preloading effects; however the waythatthe carbon pores are filled and loaded by
      different NOM fractions can be different and may create an additional negative
      impact on TCE adsorption.

PMID- 16572793
TI  - Perchlorate reduction by autotrophic bacteria in the presence of zero-valent
      iron.
AB  - A series of batch experiments were performed to study the combination of zero
      valent iron (ZVI) with perchlorate-reducing microorganisms (PRMs) to remove
      perchlorate from groundwater. In this method, H2 produced during the process of
      iron corrosion by water is used by PRMs as an electron donor to reduce
      perchlorate to chloride. Perchlorate degradation rates followed Monod kinetics,
      with a normalized maximum utilization rate (rmax) of 9200 microg g(-1) (dry wt)
      h(-1) and a half-velocity constant (Ks) of 8900 microg L(-1). The overall rate of
      perchlorate reduction was affected by the biomass density within the system. An
      increase in the OD600 from 0.025 to 0.08 led to a corresponding 4-fold increase
      of perchlorate reduction rate. PRM adaptation to the local environment and
      initiation of perchlorate reduction was rapid under neutral pH conditions. At the
      initial OD600 of 0.015, perchlorate reduction followed pseudo-first-order
      reaction rates with constants of 0.059 and 0.033 h(-1) at initial pH 7 and 8,
      respectively. Once perchlorate reduction was established, the bioreductive
      process was insensitive to the increases of pH from near neutral to 9.0. In the
      presence of nitrate, perchlorate reduction rate was reduced, but not inhibited
      completely.

PMID- 16572794
TI  - Saturation to improve pollutant retention in a rain garden.
AB  - Rain gardens have been recommended as a best management practice to treat
      stormwater runoff. Replicate rain gardens were constructed in Haddam, CT, to
      treat roof runoff. The objective of this study was to assess whether the creation
      of a saturated zone in a rain garden improved retention of pollutants. The
      gardens were sized to store 2.54 cm (1 in) of runoff. Results show high retention
      of flow; only 0.8% overflowed. Overall, concentrations of nitrite+ nitrate-N,
      ammonia-N, and total-N (TN) in roof runoff were reduced significantly by the rain
      gardens. Total-P concentrations were significantly increased by both rain
      gardens. ANCOVA results show significant reductions in TN (18%) due to
      saturation. Redox potential also decreased in the saturated garden. Rain garden
      mulch was found to be a sink for metals, nitrogen, and phosphorus, but rain
      garden soils were a source for these pollutants. The design used for these rain
      gardens was effective for flow retention, but did not reduce concentrations of
      all pollutants even when modified. These findings suggest that high flow and
      pollutant retention could be achieved with the 2.54 cm design method, but the use
      of an underdrain could reduce overall pollutant retention.

PMID- 16572795
TI  - Development of a multi-component Damage Assessment Model (MDAM) for time
      dependent mixture toxicity with toxicokinetic interactions.
AB  - A new mixture toxicity model was developed to predict the time-dependent toxicity
      of a mixture with toxicokinetic interactions directed specifically toward
      addressing biotransformation. The Damage Assessment Model (DAM), a toxicokinetic
      toxicodynamic model that describes and predicts the time-dependent toxicity of a
      single compound, was extended to a multicomponent model for mixture toxicity. The
      model assumes that cumulative damage from the parent compound, metabolites,
      and/or a biotransformation inhibitor are additive, and the sum of the cumulative
      damage determines mixture toxicity. Since incorporation of the damage addition
      hypothesis into the DAM was equivalent to an independent action model for mixture
      toxicity, it was applied to describe the combined effect of mixture components
      with potentially dissimilar modes of action. From the multicomponent DAM, a time
      dependent toxic unit model was derived and applied to determine the toxic units
      of mixture components. This model suggests a series of experimental designs
      required to assess the role of biotransformation in the toxicity of metabolized
      organic compounds and a data analysis method to separately estimate toxicodynamic
      parameters forthe parent compound and metabolites.

PMID- 16572796
TI  - Application of multi-component Damage Assessment Model (MDAM) for the toxicity of
      metabolized PAH in Hyalella azteca.
AB  - Biotransformation and time-dependent toxicity of pyrene and fluorene, in the
      presence and absence of the biotransformation inhibitor 6-propylpiperonyl butyl
      diethylene glycol ether known as piperonyl butoxide (PBO), were investigated in
      Hyalella azteca. Toxicokinetics and biotransformation were determined in both
      short- and longterm experiments. For pyrene, the uptake rate coefficient (ku = 99
      +/- 9 L kg(-1) h(-1)), elimination rate constant for parent compound (kep = 0.050
      +/- 0.008 h(-1)), biotransformation rate constant (km = 0.016 +/- 0.003 h(-1)),
      and elimination rate constant for metabolites (kem = 0.021 +/- 0.007 h(-1)) were
      determined from a short-term study. For fluorene, ku (130 +/- 30 L kg(-1) h(-1))
      and kep (1.7 +/- 0.2 h(-1)) were estimated based on km (0.015 +/- 0.002 h(-1))
      and kem (0.011 +/- 0.002 h(-1)) determined from a long-term study. At steady
      state, the percent metabolites for pyrene and fluorene were 43% and 58%,
      respectively, determined from km/(km +/- kem). Time-dependent toxicity was
      determined as both lethal water concentration and lethal body residue in the
      presence and absence of PBO. Co-exposure to PBO decreased the median lethal
      residue (LBR50) for parent pyrene and shortened the median lethal time (LT50).
      Pyrene toxicity was explained by the body residues of parent pyrene and PBO,
      where the metabolites' contribution was negligible. Forfluorene, co-exposure to
      PBO increased the LBR50 for parent fluorene and shortened the LT50. Thus,
      fluorene metabolites contributed significantly to the toxicity. Using a
      multicomponent damage assessment model, the toxicodynamic parameters, damage
      accrual rate coefficient, and damage recovery rate constant for parent pyrene and
      parent fluorene were very similar and estimated to be from 0.009 to 0.020
      micromol(-1) g h(-1) and from 0.003 to 0.013 h(-1), respectively, and the
      incipient LBR50 at the infinite time (LBR50(t = infinity)) was from 0.24 to 0.46
      micromol g(-1), respectively. These values are similar to the reported LBR50(t =
      infinity) for other nonpolar narcotics such as pentachlorobenzene (PCBz, 0.38 +/-
      0.13 micromol g(-1)) and dichlorophenylchloroethylene (DDE, 0.41 +/- 0.19
      micromol g(-1)). For fluorene metabolites, these values were 0.10 +/- 0.03
      micromol(-1) g h(-1), 0.034 +/- 0.021 h(-1), and 0.33 +/- 0.23 micromol g(-1),
      respectively. However, for pyrene metabolites, since toxicity of pyrene
      metabolites was negligible, the parameters could not be estimated.

PMID- 16572797
TI  - Effect of cadmium on the interaction of 17beta-estradiol with the rainbow trout
      estrogen receptor.
AB  - The widely reported negative effects of xenoestrogens on the endocrine system of
      aquatic organisms gave raise to public concern and led to a number of screening
      and testing initiatives on the international level. Recent studies indicated that
      not only organic chemicals but also certain heavy metals, including cadmium, can
      mimic the effects of the endogenous estrogen receptor agonist 17beta-estradiol
      (E2) and lead to estrogen receptor activation. While the effects of cadmium on
      the endocrine system and its potential to harm living organisms are no longer in
      doubt, the exact mode of action is still essentially unknown. In the present
      study we utilized the rainbow trout ER alpha ligand binding domain (rtER-LBD)
      fused to glutathione-S-transferase, to study noncovalent interactions between
      cadmium and the rtER-LBD. ICP-MS data showed that the Cd uptake by the rtER-LBD
      was strongly pH-dependent. Previous results showing that Cd shields Cys residues
      of the rtER-LBD against chemical modification, and competitive binding
      experiments reported here provide insights into the specificity of the
      interaction of cadmium with the ER hormone binding cavity. It could, for
      instance, be shown that most of the cadmium adsorbed to the protein could be
      released into solution either under denaturing conditions, or by stripping from
      the protein surface using EDTA at physiological conditions. Competitive binding
      experiments using radio-labeled estradiol showed that, in contrast to previously
      published data, E2 has an affinity an order of magnitude higher for the ER than
      for Cd. ICP-MS experiments showed that, despite its higher affinity, increasing
      E2 concentrations were unable to replace Cd from the rtER-LBD that had been
      preequilibrated with Cd. These findings were independently confirmed by the [3H]
      E2 binding assay. At the same time both ICP-MS and the [3H]-E2 binding assay
      showed that increasing Cd concentrations not only lead to a decrease in the
      specific estradiol binding, but also to the release of E2 from the
      preequilibrated rtER-LBD. The gradual release of [3H]-E2 from the rtER-LBD
      following incubation with increasing Cd concentrations indicates either direct
      competition for the same binding site or Cd-induced conformational changes
      resulting in the release of estradiol.

PMID- 16572798
TI  - Bioaccessibility of arsenic(V) bound to ferrihydrite using a simulated
      gastrointestinal system.
AB  - The risk posed from incidental ingestion to humans of arsenic-contaminated soil
      may depend on sorption of arsenate (As(V)) to oxide surfaces in soil. Arsenate
      sorbed to ferrihydrite, a model soil mineral, was used to simulate possible
      effects on ingestion of soil contaminated with As-(V) sorbed to Fe oxide
      surfaces. Arsenate sorbed to ferrihydrite was placed in a simulated
      gastrointestinal tract (in vitro) to ascertain the bioaccessibility of As(V) and
      changes in As(V) surface speciation caused by the gastrointestinal system. The
      speciation of As was determined using extended X-ray absorption fine structure
      (EXAFS) analysis and X-ray absorption near-edge spectroscopy (XANES). The As(V)
      adsorption maximum was found to be 93 mmol kg(-1). The bioaccessible As(V) ranged
      from 0 to 5%, and surface speciation was determined to be binuclear bidentate
      with no changes in speciation observed post in vitro. Arsenate concentration in
      the intestine was not constant and varied from 0.001 to 0.53 mM for the 177 mmol
      kg(-1) As(V) treated sample. These results suggest that the bioaccessibility of
      As(V) is related to the As(V) concentration, the As(V) adsorption maximum, and
      that multiple measurements of dissolved As(V) in the intestinal phase may be
      needed to calculate the bioaccessibility of As(V) adsorbed to ferrihydrite.

PMID- 16572799
TI  - The role of chlorine ion cotransport in the regulation of rest potential and
      osmotic homeostasis in eartearthworm somatic muscle cells.

PMID- 16572800
TI  - Effect of 70-kDa heat shock protein on interferon-gamma production by human
      natural killers.

PMID- 16572801
TI  - Stimulation of cell proliferation and apoptosis in the presence of amino acids in
      organotypic culture of tissues of different degree of maturity.

PMID- 16572802
TI  - The effects of synthesized analogs of vasotocin on water and ion excretion by the
      rat and monkey kidneys.

PMID- 16572803
TI  - Extrahypothalamic corticoliberin receptors regulate the reinforcing effects of
      self-stimulation.

PMID- 16572804
TI  - Antioxidant N-acetylcysteine modifies the purinergic modulation of spontaneous
      postsynaptic potentials in the newborn rat hippocampus.

PMID- 16572805
TI  - Does breathing rate affect the thermal pattern of the human face?

PMID- 16572806
TI  - Adrenergic and cholinergic activation of calcium signals in cultured postnatal
      skeletal myocytes of the rat.

PMID- 16572807
TI  - Changes in mdg1 and mdg2 location pattern at oppositely directed selection by a
      qualitative trait in an isogenic Drosophila melanogaster strain.

PMID- 16572808
TI  - A decrease in the dose of the lgl tumor suppressor increases life span of
      Drosophila in stress and is related to the maternal effect.

PMID- 16572809
TI  - Relationship of the morphogenesis of Thielavia terrestris (Apinis) Malloch et
      Cain with previous culture conditions.

PMID- 16572810
TI  - A case of anomalous chloroplast inheritance in crosses of garden pea involving an
      accession of wild subspecies.

PMID- 16572811
TI  - Estimation of stoichiometry of marker sequences of the sugar beet (Beta vulgaris)
      mitochondrial genome by real-time PCR.

PMID- 16572812
TI  - Ontogenetic transformations of legs in Triturus karelinii and T. dobrogicus,
      representative of subgenus T. cristatus (Caudata).

PMID- 16572813
TI  - Effect of psychoemotional state on growth and metastasis of Lewis tumor in mice.

PMID- 16572814
TI  - Analysis of regulatory mechanisms in the density-testis-spermatozoa-fertility in
      small mammals.

PMID- 16572815
TI  - Highly pathogenic influenza virus H5N1 found in western Siberia is genetically
      related to viruses that circulated in Southeast Asia in 2003-2005.

PMID- 16572816
TI  - Genetically determined subdivision of human populations with respect to the risk
      of breast cancer in women.

PMID- 16572817
TI  - The destructive effect of enhanced gravity on the inertial mass in the statocysts
      of Helix lucorum.

PMID- 16572818
TI  - Analysis of cell nuclear supramolecular structures during chromatin activation.

PMID- 16572819
TI  - On the homology of the caudal tagma in Cladoceromorpha (Crustacea: Branchiopoda).

PMID- 16572820
TI  - Immunocytochemical localization of atrial natriuretic peptide in mast cells of
      adult brown frog Rana temporaria.

PMID- 16572821
TI  - Disturbance pheromone in the common toad (Bufo bufo) larvae: the possible
      communicative role of ammonium-containing excretions.

PMID- 16572822
TI  - Stress and haploadaptability of the lgl tumor suppressor: population and genetic
      studies on Drosophila.

PMID- 16572824
TI  - The "quantization" of sensitivity coefficients is preserved in microbial
      populations heterogeneous with respect to growth rate and age.

PMID- 16572823
TI  - An increase in the dopamine level accelerates sexual maturation of Drosophila
      melanogaster deficient in the juvenile hormone.

PMID- 16572825
TI  - Humic substances as natural photoinducers degrading pesticides in the
      environment.

PMID- 16572826
TI  - A new epigene property: metastable epigenotypes.

PMID- 16572827
TI  - Detection of viral dsRNA in the yeast Saccharomyces bayanus.

PMID- 16572828
TI  - New data on the migration of the family Elephantidae (Mammalia, Proboscidea) in
      Eurasia.

PMID- 16572829
TI  - Clonal diversity and rare phenes in Taraxacum officinale s.l. coenopopulations
      from the East-Ural radioactive trace zone.

PMID- 16572830
TI  - The role of phosphatidylinositol-3-kinase in the formation of oxygen radicals by
      phagocytes in whole blood samples from patients with coronary heart disease.

PMID- 16572831
TI  - The role of mitochondria in the initiation of calcinosis in transplants of heart
      valves and vessels.

PMID- 16572832
TI  - Analysis of expression of genes specific for pluripotent and primordial germ
      cells in human and mouse embryonic stem cell lines.

PMID- 16572833
TI  - [Taxol-producing fungi: a new approach to industrial production of taxol].
AB  - Produced by and purified from Taxus brevifolia, Taxol (paclitaxel) has become a
      widely used cancer drug in clinic. Due to the rapid growing market, current
      industrial production of taxol by semi-synthesis that consumes large amount of
      Taxus trees cannot meet the requirement of the market. The discovery of taxol
      producing fungus Taxomyces andeanae, an endophyte of T. brevifolia, by Stierle et
      al (1993), paves a new way to the production of the drug, i.e. employing large
      scale fungal fermentation to make Taxol at lower cost and yet higher yield. This
      review discusses the present problems in taxol production in pharmaceutical
      industry, the finding and research progress on taxol-producing fungi, and the
      potential application of fungal fermentation to manufacture this important drug.

PMID- 16572834
TI  - [Development and challenge of modified hemoglobins as red blood cell
      substitutes].
AB  - The problems of blood shortage and the virus infection risk of blood transfusion
      have promoted the study of blood substitutes. Modified hemoglobin has become the
      focus of the challenges research because of its excellent oxygen carrying
      ability. To overcome the toxicity effect on direct use of purified native
      hemoglobin, various modification technologies have been developed, including
      diaspirin cross-linking, glutaraldehyde polymerization, O-raffinose
      polymerization, polyethylene glycol conjugation, liposome encapsulation and
      biodegradable polymer encapsulation. Some of the products have been in clinical
      trials, and one of the products has been approved in a country for clinical use.
      Research on red blood cell substitutes in China has also developed fast. This
      paper provides an overview of the history and current status in development of
      different hemoglobin-based red blood cell substitutes, especially the problems
      encountered, the challenges faced, and the prospects in future.

PMID- 16572835
TI  - [Large recombinant protein displayed on filamentous phage surface and its
      interaction with small molecule].
AB  - Recombinant proteins were expressed as fusions with the phagemid system of pHEN
      KM13 and the characteristics and activities of the fusion proteins displayed on
      the surface of filamentous phagintain the were studiedon abilty. The altered
      titer of rescued phages from the phagemid system after trypsin treatment
      indicated the relative quantity of the phages displaying fusion proteins. The
      rescue phages displayed foreign proteins could keep the bacterial infection
      ability, while the bald phage without foreign protein displayed on its surface
      was sensitive to trypsin treatment and lost the bacterial infection ability. To
      determine the upper limit for filamentous phage display, four recombinant
      proteins, glutathione-S-transferase and glutathione-S-transferase fused with
      three various size peptide linkers, were fused to N terminus of capsid protein
      gp3 and rescued by helper phage KM13. The rescued phages which displayed fused
      protein with the size of 40kD or less maintain the infection ability. To assay
      the activity of the phage displayed protein, the known small molecule probe was
      used in the interaction study with protein incorporated on phage surface. Results
      showed that the glutathione-S-transferase on phage surface still bound to
      glutathione specifically. It indicated that the glutathione-S-transferase
      displayed on phage surface was correctly folded and functionally active. The
      results demonstrated that it was feasible to use small molecule probes to
      interact with the protein displayed on phage surface. In turn, the method
      described here also demonstrated that phage display system could be utilized to
      investigate the interactions between protein and small molecules.

PMID- 16572836
TI  - [Improvement of the thermostability of xylanase by N-terminus replacement].
AB  - The hybrid xylanase TB was constructed by the substitution of the N-terminus
      segment of the Streptomyces olivaceoviridis xylanase XYNB with corresponding
      region of Thermomonosporafusca xylanase TfxA. The hybrid gene tb, encoding the
      TB, was correctly expressed in Escherichia coli BL21 and Pichia pastoris GS115.
      TB was purified and its enzymatic properties were determined. The results
      revealed that the optimal temperature and optimal pH of TB were at 70 degrees C
      and 6.0, which have been obviously improved compared with those of XYNB. The
      thermostability of TB were all about six-fold of XYNB's after incubating the
      properly diluted enzyme solutions at 80 degrees C and 90 degrees C for 3min,
      respectively. The pH stability of TB was 5 to approximately 9, which was narrower
      than that of XYNB. Still, TB remains a high specific activity as XYNB does.
      Analysis of a homology modeling and sequence similarity were used to reveal the
      factors influencing the enzymatic properties of TB and the discussion for the
      relationship between structure and function of xylanase was given.

PMID- 16572837
TI  - [Functional expression of an omega-3 fatty acid desaturase gene from Glycine max
      in Saccharomyces cerevisiae].
AB  - Alpha-linolenic acid(ALA, C18:3delta9,12,15 ) is an essential fatty acid which
      has many sanitary functions to human. However, its contents in diets are often
      not enough. In plants, omega-3 fatty acid desaturases(FAD) catalyze linoleic
      acid(LA, C18:2delta9,12) into ALA. The seed oil of Glycine max contains high
      level of ALA. To investigate the functions of Glycine max omega-3FAD, the cDNA of
      GmFAD3 C was amplified by RT-PCR from immature seeds, then cloned into the
      shuttle expression vector p416 to generate the recombinant vector p4GFAD3C. The
      resulting vector was transformed into Saccharomyces cerevisiae K601 throuth LiAc
      method. The positive clones were screened on the CM(Ura-) medium and identified
      by PCR, and then cultured in CM (Ura-) liquid medium with exogenous LA in 20
      degrees C for three days. The intracellular fatty acid composition of the
      engineering strain Kp416 and Kp4GFAD3C was analyzed by gas chromatography (GC). A
      novel peak in strain Kp4GFAD3C was detected,which was not detectable in control,
      Comparison of the retention times of the newly yielded peak with that of
      authentic standard indicated that the fatty acid is ALA. The content of ALA
      reached to 3.1% of the total fatty acid in recombinant strain, the content of LA
      correspondingly decreased from 22% to 16.2% by contrast. It was suggested that
      the protein encoded by GmFAD3 C can specifically catalyze 18 carbon PUFA
      substrate of LA into ALA by taking off hydrogen atoms at delta15 location. In
      this study, we expressed a Glycine max omega-3 fatty acid desaturase gene in S.
      cerevisiae; An efficient and economical yeast expressing system(K601-p416 system)
      which is suitable for the expression of FAD was built.

PMID- 16572838
TI  - [Study on immunogenicity of the N-terminal polypeptide of RTX toxin I of
      Actinobacillus pleuropneumoniae].
AB  - ApxI is one of the most important virulence factors of Actinobacillus
      pleuropneumoniae (APP). To study the immunogenicity of the ApxI, the complete
      coding sequence (3146bp) and its 5'-terminal 1140 bp fragment of the apxIA gene
      were separately cloned into the prokaryotic expression vector pET-28a, and
      expressed in the E. coli BL21 (DE3) with induction by IPTG. The expression
      products, rApxIA and rApxIAN, were present in a form of inclusion bodies and
      showed the same immunological reactivity as natural ApxI (nApxI) in Western-blot
      analysis. BALB/c mice were intraperitoneally immunized with the rApxIA, rApxIAN
      and nApxI respectively. The serum antibody levels of the rApxIAN immunized mice
      were significantly lower than those immunized with rApxIA or nApxI in an ApxI
      specific ELISA, but serum neutralization test demonstrated that immunized mice
      with rApxIAN, rApxIA and nApxI could generate similar levels of antibodies
      neutralizing the hemolytic activity of the natural ApxI. The rApxIAN was able to
      elicite 80% protection rate against APP serovar 1 and 100% against serovar 2 when
      challenged at a dose of one LD50 after 2 weeks of boost immunization.

PMID- 16572839
TI  - [Cloning, soluble expression and characterization of human sBCMA].
AB  - BCMA is one of the transmembrane receptors belonging to BAFF and APRIL. In order
      to identify the feasibility of sBCMA as decoy receptor and obtain active sBCMA
      for its structural and functional research, full length of hBCMA was amplified
      with total RNA from Raji cell line by RT-PCR, and the cDNA encoding the
      extracelluar soluble domain of hBCMA was inserted into pET43.1a(+) vector. The
      recombinant vector pET43.1a(+)-sBCMA was transformed into E. coli Origami B(DE3)
      pLyS which is helpful for disulfide bond construction of expression proteins.
      After IPTG induction, the recombinant protein was expressed as soluble fusion
      protein, sBCMA-NusA-His6, and identified by western blotting. Then the target
      protein was purified by Ni(+)-chelating Sepharose Fast Flow. The binding activity
      between recombinant sBCMA and BAFF was detected by ELISA. Also, Recombinant sBCMA
      inhibited proliferation of mouse B cell stimulating by rhsBAFF. It was proved
      that recombinant sBCMA has good bioactivity and the method to express those
      proteins rich in disulfide bond is feasible and effectual.

PMID- 16572840
TI  - [Molecular cloning of tomato LeHsp110/ClpB gene and its effect on the
      thermotolerance in plant].
AB  - The heat shock protein ClpB is a member of the Clp family and functions as
      molecular chaperones. ClpB is related to the acquired thermotolerance in
      organisms. A cDNA of 3144 bp was screened out of a tomato cDNA library. The
      polypeptide deduced from the longest ORF contains 980 amino acid residues, and
      was classified into HSP100/ClpB family based on the result of molecular
      phylogenesis analysis. Thus it was named as LeHSP110/ClpB according to its
      calculated molecular weight. LeHSP110/ClpB was characteristic of heat
      inducibility but no constitutive expression, and was demonstrated to locate in
      chloroplastic stroma. An antisense cDNA fragment of LeHsp110/ClpB under the
      control of CaMV 35S promoter was introduced into tomato by Agrobacterium
      tumefactions-mediated method. At high temperature, the mRNA levels of
      LeHsp110/ClpB in antisense transgenic plants were lower than those in control
      plants. The PS II of transgenic plants is more sensitive to high temperature than
      that of control plants according to data of Fv/Fm. These results clearly showed
      that HSP110/ClpB plays an important role in thermotolerance of high plants.

PMID- 16572841
TI  - [Prokaryotic expression of functional PTEN in Escherichia coli and preparation of
      polyclonal antibody].
AB  - PTEN, a dual-specificity phosphatase, exerts its tumor-suppressive effects
      through the inhibition of cell cycle progression and cell immigration, therefore
      could be an important candidate for tumor-suppression. As study on prokaryotic
      expression of PTEN and its anti-tumor functions has not been reported, the
      present study aims at an efficient expression of functional PTEN in Escherichia
      coli and the investigation of its tumor-suppression activity. PTEN cDNA cloned in
      our lab previously was recombined into prokaryotic expression vector pET-44a(+)
      to construct pET-PTEN (pEP) and pET-Nus-PTEN (pENP). PTEN was fused with 6 x His
      tag in pEP, and with Nus in pENP, which could be useful for a stable and soluble
      expression. The recombinant vectors were transformed into both BL21 (DE3) (BL)
      and Rosetta-gami (DE3) pLysS (RG). The former is a normal expression host while
      the latter is optimized for expression of eukaryotic genes and folding of target
      proteins. On the induction of 0.5mmol/L IPTG, 55kD and 118kD specific protein
      bands were observed, corresponding to His-PTEN and Nus-PTEN fusion proteins,
      respectively. Western blot analysis showed the recombinant fusion proteins could
      react with PTEN polyclonal antibody. The recombinant HTEN was expressed both in
      soluble fraction and inclusion body. Higher expression levels of recombinant PTEN
      were obtained in BL (His-PTEN: 10.3%; NusA-PTEN: 18.7%), whereas the higher
      percentages of soluble recombinant proteins were observed in RG (His-PTEN: 4.7%;
      Nus-PTEN: 6.6%). The obtained recombinant fusion proteins were purified by
      affinity chromatography and were showed to be homogeneous in SDS-PAGE. In tumor
      suppression experiments, His-PTEN was proved to have significant inhibition on
      growth of mice solid tumor with an inhibitory ratio of 58.76%, and on the
      proliferation of DU-145 tumor cells with an inhibitory ratio of 46.16%. The cell
      cycle progression of DU-145 tumor cells was also arrested from G0/G1 to S phase.
      His-PTEN from RG was proved to have significantly higher tumor-suppression
      activity than that from BL, indicating that there may be some advantages for
      eukaryotic genes to be expressed in the former host. This is the report of
      functional recombinant PTEN expressed in Escherichia coli. Purified His-PTEN was
      used for immunizing Kunming mice, and ascitic polyclonal antibodies raised
      against His-PTEN were generated using sarcoma 180 cells. At 1:2000 dilution, the
      antibodies could interact with PTEN by western blot. The present study has laid a
      foundation for application of PTEN in cancer therapy.

PMID- 16572842
TI  - [Acute toxicity and immunoprotection of recombinant apxI toxin of Actinobacillus
      pleuropneumoniae in mice].
AB  - Acute toxicity and immunoprotection of Actinobacillus pleuropneumoniae (APP) ApxI
      toxin recombinant proteins (include crude inclusion bodies and refolded
      recombinant protein) were evaluated in mice, and compared with the natural ApxI
      extracted from culture supernatant of APP serotype 10. In the acute toxicity
      experiment, the three proteins were intraperitoneally injected into Kunming mice
      in a dose of 200microg per mouse. The body and organ weight, heamatological and
      biochemical indexes were examined at 24h, 7 days and 14 days post administration.
      There was no death after the intraperitoneal administration of the three
      proteins, and no significant change was found in the body weight, organ indexes,
      heamatological and biochemical indexes. To study their immunoprotection, the
      three proteins were emulsified with Freund's adjuvant respectively and vaccinated
      the mice twice with a 2-week of interval. Two weeks after the second vaccination,
      the mice were challenged intraperitoneally with a lethal dose of APP serotype 10
      (1.09 x 10(8) cfu), and serums were examined by an ApxI-specific ELISA. The
      results revealed that the recombinant protein had a good immunogenicity and could
      induce protection immune reaction.

PMID- 16572843
TI  - [High-level production of neutral endoglucanase 1 in Pichia pastoris].
AB  - The gene (eg1) encoding for novel endoglucanase 1 was cloned previously from
      Chinese straw mushroom Volvariella volvacea. EG1 has high thermal stability and
      optimal pH at neutral and shows great potential in textile and paper industry
      applications. To improve the expression level of EG1 in Pichia pastoris, the
      increasing copy number of clone, and its high cell density fermentation in 3.2L
      fermenter for its high-level expression were investigated in this work. By
      electro-transformation of pPICZalphaB-egl into GS115EG11 integrated with single
      copy of eg1 gene, A resistant transformant with 3.8 times higher level expression
      than GS115EG11 was screened from YPDSZ plate containing 2000 microg/mL of Zeocin.
      The effect of initial cell density, pH and methanol on its expression and biomass
      accumulation was evaluated in shaking culture. Optimal EG1 production was
      observed when initial cell density OD600 was 5.0. EG1 production and biomass
      accumulation did not seem to vary when cells were induced at different pH values.
      Both of EG1 and cell density were found to increase with higher methanol
      concentrations, reaching 62.48 IU/mL and 31.7 (OD600) respectively after 120 h
      induction with 2.0% (V/V) methanol compared to 30.24 IU/mL and 17.79 (OD60) with
      0.25% methanol induction. EG1 expression was further increased by 6.4 times
      higher than shaking culture after 95.5 hours induction with methanol in fed-batch
      fermentation, so totally 34 times higher than that for GS115EG11 was achieved by
      screening of high Zeocin resistant clone and high cell density fermentation. The
      production of EG1 with 543.36IU/mL CMC activity and 8.80mg/mL protein expression
      was obtained in Pichia pastoris.

PMID- 16572844
TI  - [Isolation of BADH gene promoter from Suaeda liaotungensis and its sequence
      analysis].
AB  - In this study, the 5' -flanking proximal region of stress-induced gene encoding
      betaine aldehyde dehydrogenase was isolated by Adaptor-PCR and TAIL-PCR from
      halophyte Suaeda liaotungensis. 1993 bp sequence was obtained by sequencing. The
      transcription start site, which localized at 62 bases upstream of the start ATG,
      was predicted using TSSP-TCM program. The functional elements were analysed by
      PLACE programm. The SlBADH gene promoter contains the basic elements: TATA-box,
      CAAT-box, and stress-induced elements: salt responsed element, cold, dehydration,
      ABA and frozen responsed elements, WUN responsed elements and HSE. Obtaining the
      promoter of betaine aldehyde dehydrogenase gene from Suaeda liaotungensis
      provides a foundation for analyzing the stress-induced promoter elements,
      studying the relationship between structure and founction of the promoter, and
      investigating the molecular mechanism of BADH gene regulation.

PMID- 16572845
TI  - [Recombinant Aspergillus niger glucose oxidase expressed in Trichoderma reesei].
AB  - It was expected that recombinant Aspergillus niger glucose oxidase could be
      expressed in Trichoderma reesei with stable activity. T. reesei CBHI promoter-
      CBHI ss. gene--A. niger glucose oxidase gene--T. reesei CBHI terminator--A.
      nidulans gpd promoter--E. coli Hygromycin B phosphotransferase gene--A. nidulans
      trpC terminator--pUC19 (pCBHGOD) vector was constructed in E. coli DH5alpha by
      PCR application and gene cloning methods. T. reesei QM9414 protoplast was
      transformed by T. reesei CBHI promoter-CBHI ss. Gene--A. niger glucose oxidase
      gene--T. reesei CBHI terminator-A. nidulans gpd promoter--E. coli Hygromycin B
      phosphotransferase gene--A. nidulans trpC terminator linear DNA fragment (CBHGOD
      fragment) that was made by digestion of pCBHGOD with Kpn I. T. reesei mutant
      clone with homologous recombinant A. niger glucose oxidase gene was selected by
      PCR method. Recombinant glucose oxidase was produced by mutant T. reesei strain
      under induction of wheat straw for 5 days. Recombinant glucose oxidase molecular
      mass was showed the same as native A. niger glucose oxidase standard from Sigma
      company by Western blot analysis. Recombinant glucose oxidase activity was 25u/mL
      in medium. The yield was 0.5 g/L in comparison with Sigma company glucose oxidase
      standard. There was no recombinant GOD degradation during Trichoderma reesei
      cultivation that was showed in Western blot analysis. Trichoderma reesei has
      capability to be a new recombinant host for Aspergillus niger GOD production.

PMID- 16572846
TI  - [High level expression, purification and cytotoxicity of IL-10(18-57)-PE40].
AB  - The objective of the experiment is to explore the purification and production of
      immunotoxin. The chimeric toxin, which is composed of 40 peptides of interleukin
      10 (from amino acids 18 to 57) fused to a mutant form of Pseudomonas extoxin (PE)
      devoid of its native cell recognition domain. Two kinds of prokaryotic expression
      vector containing the chimeric toxin IL-10(18-57)-PE40 were constructed
      respectively. After induction of IPTG for 3 hours, IL-10(18-57)-PE40 was
      expressed highly in cytoplasmic fraction in Rosettablue(DE3), and was directed to
      periplasmic space as soluble form in E. coli BL21(DE3)pLysS . Western -blotting
      showed that the expressed protein could react with the specific rabbit sera
      against LHRH-PE40. With the application of salting out of (NH4)2SO4, hydrophobic
      interaction chromatography, Cu-affinity chromatography and anion exchange
      chromatography, the purity of IL-10(18-57)-PE40 was about 96%. The cytotoxicity
      assay, Cell-ELISA and fluorescent antibody test support the hypothesis that IL
      10(18-57) based ligand-mediated cytotoxicity can serve to target cytotoxic agents
      in vitro.

PMID- 16572847
TI  - [Metabolism of recombinant CHO-GS cell reducing of toxic effect of ammonia].
AB  - The toxic effect of ammonia on rCHO-GS cell decreased obviously due to the
      transfection of GS system in serum-free culture. The maximum cell density, 15.6 x
      10(5) cells/mL was obtained in the culture with 1.42 mmol/L ammonia. The growth
      of rCHO-GS cell was inhibited with an increased ammonia concentration. However, a
      cell density of 8.9 x 10(5) cells/mL was obtained when the concentration of
      ammonia was 12.65mmol/L. The intracellar metabolic pathways were affected due to
      the decrease of the toxic effect of ammonia on rCHO-GS cell. With the increase of
      initial ammonia concentration from 0.36mmol/L to 12.65mmol/L, the yield
      coefficients of cell to glucose and lactate to glucose decreased. The activities
      of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH)
      increased by 43%, 140% and 25%, respectively, indicating that the utilization of
      glucose increased and the glycolysis pathway was more prone to efficient energy
      metabolism pathway. An increased activity of glutamate-pyruvate aminotransferase
      (GPT) showed that the conversation from glutamate to alpha-ketoglutarate was
      shifted to glutamate-pyruvate transamination pathway. The deamination pathway was
      inhibited due to a decreased activity of glutamate dehydrogenase. In addition,
      the number of cells in G0/G1 phase increased and the specific production rate of
      recombinant protein increased by 2.1-fold with the increase of initial ammonia
      concentration from 0.36mmol/L to 12.65mmol/L.

PMID- 16572848
TI  - [Effects of hydrodynamic on aggregates formation, growth and metabolism of HEK293
      cells in suspension culture].
AB  - By using the size distribution of cell aggregates, viable cell density, cell
      viability, specific consumption rate of glucose (q(glc)), specific production
      rate of lactate (q(lac)) and lactate transform rate (Y(lac/glc)) as the
      evaluation indexes, the effects of hydrodynamic on aggregates formation, growth
      and metabolism of HEK293 cells in suspension culture were examined in 250mL
      spinner-flasks by setting the agitation rates at 25, 50, 75 and 100r/min,
      respectively. It was found that agitation plays an important role in HEK293 cell
      aggregates formation and cell aggregates size distribution. After 7d cultivation
      in spinner-flasks operated at 50r/min and 75r/min, the average diameter of HEK293
      cell aggregates was 201 microm and 175 microm, respectively, with the fraction of
      aggregates larger than 225 microm less than 10%. The cell viability was kept
      above 90% with the metabolic indexes, including q(glc), q(lac) and Y(lac/glc)
      kept constant. These results demonstrated that hydrodynamic derived from the
      proper agitation play a decisive role in controlling the formation and size
      distribution of HEK293 cell aggregates, and provided sufficient mass transfer to
      support the normal growth and metabolism of HEK293 cells in suspended aggregates.

PMID- 16572849
TI  - [Hairy root induction and plant regeneration of crownvetch (Coronilla varia L.)
      transformed by Agrobacterium rhizogenes].
AB  - An efficient system of genetic transformation and plant regeneration via somatic
      embryogenesis was established in crownvetch (Coronilla varia L.) by infecting the
      segments of cotyledons and hypocotyls of 15d-old seedlings with Agrobacterium
      rhizogenes strain 15834. Hairy roots were produced directly from the wounded
      surface of the explants or via calluses on hormone-free Murashige and Skoog (MS)
      medium after infection by A. rhizogenes. Transformed roots grew rapidly either on
      solid or liquid MS medium, and exhibited typical hairy root phenotypes. The
      highest transformation frequency (87.4%) was achieved by preculturing cotyledons
      for 2d and pre-treating the A. rhizogenes with suitable concentration of
      acetosyringone at logarithmic phase (OD600 = 0.8). The embryogenic calluses with
      100% induction frequency were induced from hairy roots on MS medium containing
      0.2mg/L 2,4-D, 0.5mg/L NAA and 0.5mg/L KT. Globular-, heart-, torpedo-, and
      cotyledon shaped somatic embryos were produced orderly and developed into
      plantlets when transferred the embryogenic calluses on MS medium supplemented
      with 0.5mg/L KT, 0.2mg/L IBA and 300mg/L proline. The transformed plants did not
      show differences in morphology except abundant lateral root branches compared to
      the non-transformed plants. However, the contents of 3-nitropropanic acid in
      hairy roots and leaves of one of 5 transformed clones were 57.68% and 58.17% in
      roots and leaves of untransformed plants, respectively. Opine paper
      electrophoresis revealed the integration and expression of TR-DNA. PCR analysis
      confirmed that the TL-DNA including 654 bp rol B sequence was inserted into the
      genome of transformed hairy roots and their regenerated plants.

PMID- 16572850
TI  - [Immobilization of lipase on macroporous resin and its application in synthesis
      of biodiesel in low aqueous media].
AB  - Lipase from Candida sp. 99-125 was immobilized by physical adsorption onto
      macroporous resins. The results showed that the nonpolar resin NKA was the best
      carrier used in low aqueous media. 98.98% of degree of immobilization can be
      achieved when the adsorption procedure was performed in the presence of heptane.
      The hydrolytic activity and the apparent activity recovery of lipase adsorbed on
      resin in heptane was 4.07 and 3.43 times higher than that of lipase adsorbed in
      sodium phosphate buffer, respectively. The catalytic properties of immobilized
      lipase for production of biodiesel in low aqueous media were studied. Immobilized
      lipase displayed the highest activity when the crude enzyme/resin weight ratio
      was 1.92:1 and the water content(water/oil weight ratio) was 15% at 40 degrees C
      under pH 7.4. As lipase was adsorbed on NKA in heptane to produce biodiesel, the
      batch conversion rate can reach 97.3% when a three-step methanolysis protocol was
      used. After 19 consecutive batches, the conversion rate remained 70.2%.

PMID- 16572851
TI  - [Studies on phage displayed mimotopes of a protective monoclonal antibody (SSj14)
      against Schistosoma japonicum].
AB  - To obtain peptides mimicking epitope of a protective McAb SSjl4 specific to
      Schistosoma japonicum and investigate their immuno-protection effects. A phage
      random 12 peptide library was screened using purified McAb SSj14, 33 clones were
      picked up for specificity identification by ELISA. The epitope of each positive
      clones were detected by the sequencing analysis technique. The antigenicity of
      three positive clones (P1, P2 and P11) and their mixture cock-tail were further
      confirmed by Western-blotting, and their protective efficiency were evaluated by
      mice vaccination experiment. IL-12 level between the vaccinated mice and control
      mice were compared. 30 positive phage clones were obtained, which represented 11
      different epitopes respectively, there were a similar sequence "H-N/Q-X-S-P/F-X-X
      L-A-T" among all of the epitopes. Western-blotting showed that all of the three
      tested clones were recognized by McAb SSj14. Significant adult worm reduction
      (13.84% to approximately 52.83%), liver tissue egg reduction (34.17% to
      approximately 65.47%) as well as fecal egg reduction (28.89% to approximately
      73.78%) were observed in mice vaccinated with phages of P1, P2, P11 and mixture
      of three clones when compared with those of the blank control group, among them,
      the mice vaccinated with the mixture of phage clones got higher protection than
      any of the mice injected with only one kind of clone phages. At the same time,
      the IL-12 level in serum of vaccinated mice was found higher than those of the
      blank control one, this suggest that IL-12 may correlate with the protective
      efficiency induced by the clone phages. The study provides a new way for
      developing an effective vaccine against S. japonicum.

PMID- 16572852
TI  - [Screening and detecting of proteins interacting with mPem].
AB  - mPem, a homeobox gene, is expressed in a time and stage specific manner during
      murine ontogeny. Pem transcripts are abundant in 7- and 8-day mouse embryos, but
      decrease precipitously thereafter. On Day 9 they become abundant in placenta and
      yolk sac, persisting there until parturition. Although Pem transcripts are not
      detectable in most of adult tissues, they are present in reproductive system such
      as testis, epididymis and ovary. This indicates a important role for Pem during
      embryogenesis and reproductive development. To study the function of mPem
      protein, we used a GAL4 based yeast two-hybrid assay to screen a 7-day mouse
      embryo library with full-length of mPem. 3 proteins were found interacting with
      mPem protein. One of theses is Mdfic. We confirmed the interaction between mPem
      and Mdfic in yeast and in vitro. Mdfic, MyoD family inhibitor domain containing,
      encodes the myoD family inhibitor domain (I-mfa domain). The interaction between
      mPem and Mdfic suggested they maybe form the transcriptional regulator complex to
      regulate embryo differentiation.

PMID- 16572853
TI  - [Construction of sugar-based microbial fuel cells by dissimilatory metal
      reduction bacteria].
AB  - Dissimilatory Metal Reduction Bacteria play an important role in the anaerobic
      environment. This kind of bacteria gains energy by coupling the oxidation of
      organic acid or sugars to the reduction of metal oxides. The graphite electrode
      rode can also be used as the final electron acceptor due to its similarity to
      solid metal oxides. Based on this biological mechanism, Dissimilatory Metal
      Reduction Bacteria Rhodoferaxferrireducens was used to construct a suit of
      microbial fuel cells with sugars as fuel, and the process and mechanism of
      electricity generation was studied. Rhodoferax ferrireducens was inoculated into
      the anode chamber in which a graphite electrode served as the final electron
      acceptor and glucose as the sole electron donor. It was showed that current
      density was up to 158mA/m2 with the resistance of 510omega at the normal
      temperature (platform voltage was around 0.46V, the effectual electrode surface
      was 57cm2). Following 20days' growth a large amount of bacteria cells attached to
      the electrode surface had been observed through the SEM images. The plandtonic
      cell protein concentration was 140mg/L and the attached biomass of electrode
      surface was 1180mg/m2 determined by the Bradford method, which indicated quite a
      few bacteria attached to the electrode. By analyzing the voltage value measured
      by the data acquisition system, it was proved that microbial electricity
      generation attributed mainly to the electrochemically and biologically active
      cells attached to the electrode, while the planktonic cells had no ability to
      catalyze electricity generation and almost had not electrochemically and
      biologically active. Furthermore, this kind of microbial fuel cells exhibited a
      good electrochemical cycle property and proved to be efficient in biomass
      utilization and energy restore since other sugars like fructose, sucrose, even
      xylose, could be oxidized and finally decomposed. Vast waste biomass in the form
      of carbohydrates is discarded in the environment. Not only is contamination of
      the environment caused by the discarded biomass, but also abundant energy stored
      in the biomass is drained away in vain. The sugar-based microbial fuel cells
      constructed by Rhodoferax ferrireducens could effectively transform the energy
      stored in sugars into electricity. Meanwhile, the microbial fuel cells presented
      in this paper, which could work cleanly at normal temperature with a good cycle
      property, showed a promising future application in this field.

PMID- 16572854
TI  - [Stimulatory effects of some amino acids on glycerol production by Candida
      glycerinogenes].
AB  - By using some intermediate metabolites in EMP pathway and TCA cycle as the
      control, the effects of amino acid supplements on glycerol production by Candida
      glycerinogenes in shake-flask fermentations with urea as nitrogen resource were
      investigated. The results showed that ten kinds of amino acids, including L
      glutamic acid, L-glutamine, L-aspartic acid, L-asparagine, L-glycin, L-lysine, L
      tyrosine, L-proline, L-histidine, and L-serine, had strong promotional effects on
      glycerol production; The optimal concentrations of these amino acids were 0.40,
      0.45, 0.36, 0.35, 0.39, 0.36, 0.35, 0.45, 0.26, and 0.45 g/L, respectively.
      Accordingly the optimum contents of pyruvic acid, a-oxoglutarate, oxaloacetic
      acid, citrate, and succinate were 0.24, 0.42, 0.40, 0.37, and 0.38 g/L,
      respectively. The advantageous opportunities of supplement were as follows: L
      lysine at the beginning of fermentation; pyruvic acid and oxaloacetic acid at the
      fourteenth hour; L-glutamic acid, L-glutamine, L-histidine, L-proline, L-aspartic
      acid, L-tyrosine, L-glycin, alpha-oxoglutarate, and succinate at the thirtieth
      hour; and L-asparagine, L-serine, and citrate at the forty-eighth hour. The
      addition of each stimulant at the optimal conditions could significantly promote
      glycerol production, with the glycerol yield on initial glucose and its increased
      speed exceeding 60% and 16%, respectively. The possible stimulatory mechanism due
      to the amino acid supplements is that the increased intermediate metabolites
      levels from amino acids degradation may have enhanced the flux through TCA cycle,
      which improve cell energetics. Meanwhile, the shift of carbon metabolism flux at
      the glyceraldhyde-3-phosphate node can result in the incremental flux through
      glycerol biosynthesis pathway.

PMID- 16572855
TI  - [Modelling a penicillin fed-batch fermentation using least squares support vector
      machines].
AB  - The biochemical processes are usually characterized as seriously time varying and
      nonlinear dynamic systems. Building their first-principle models are very costly
      and difficult due to the absence of inherent mechanism and efficient on-line
      sensors. Furthermore, these detailed and complicated models do not necessary
      guarantee a good performance in practice. An approach via least squares support
      vector machines (LS-SVM) based on Pensim simulator is proposed for modelling the
      penicillin fed-batch fermentation process, and the adjustment strategy for
      parameters of LS-SVM is presented. Based on the proposed modelling method, the
      predictive models of penicillin concentration, biomass concentration and
      substrate concentration are obtained by using very limited on-line measurements.
      The results show that the models established are more accurate and efficient, and
      suffice for the requirements of control and optimization for biochemical
      processes.

PMID- 16572856
TI  - [Preparation of uniform-sized chitosan microspheres and application as carriers
      for protein drugs].
AB  - Chitosan microsphere has been wildly researched in controlled release of protein
      and peptide drug because of its excellent mucoadhesive and permeation enhancing
      effect across the biological surfaces. The control of the size and size
      distribution of microspheres is necessary in order to improve reproducibility,
      bioavailability, and repeatable release behavior. In this work, uniform-sized
      chitosan microspheres containing insulin were prepared by a novel membrane
      emulsification technique combined with glutaraldehyde crosslinking method. In
      order to prepare uniform-sized chitosn microspheres, it is necessary to modify
      hydrophilic membrane into hydrophobicity. It is found that there exists a linear
      relationship between the size of chitosan microspheres and pore size of the
      membrane used, so it is easy to control the size of microspheres by using
      membranes with different pore size. In this study, the effect of different amount
      of crosslinker and crosslinking time on microspheres' morphology, encapsulation
      efficiency (EE) and release profile of drug in vitro were investigated. It is
      shown that the morphology of microspheres is more smooth and spherical, and the
      release rate is slower with the increase of amount of glutaraldehyde and
      prolongation of crosslinking time. When the molar ratio of amino group of
      chitosan to aldehyde group of glutaraldehyde is 1:0.7, and crosslinking time is 1
      h, the highest EE was obtained (about 65%). Date obtained suggest that chitosan
      microspheres prepared by this new method would be a promising system for
      controlled release of protein drugs.

PMID- 16572857
TI  - [Effect of osmotic pressure on nitrification].
AB  - The effect of osmotic pressure on nitrification was investigated in the internal
      loop air-lift nitrifying reactor. When influent ammonia concentration is kept at
      420mg x L(-1) and influent osmotic pressure is increased from 4.3 to 18.8 x 10(5)
      Pa, the ammonia conversion of the nitrifying bioreactor is maintained between 93%
      and 100%. After influent osmotic pressure is further increased to 19.2 x 10(5)Pa,
      the ammonia conversion goes down to 69.2%. The influence of osmotic pressure on
      nitrification takes place without any alarm and the critical osmotic pressure is
      between 18.8 x 10(5) and 19.2 x 10(5) Pa. During osmotic stress, the nitrifying
      bacterial populations in the activated sludge become simplified, the cell size
      becomes smaller, the inner membrane becomes less and some unknown inclusion
      particles are formed. The cell structure is restored as soon as the osmotic
      pressure is removed. Addition of potassium is able to relieve the effect of
      osmotic pressure on nitrification. The nitrifying activity of the activated
      sludge is stimulated by the osmotic stress, and the specific ammonia conversion
      is increased from 0.083 kg x kg(-1) x d(-1) to 0.509 kg x kg(-1) x d(-1) and
      2.569 kg x kg(-1) x d(-1), respectively.

PMID- 16572858
TI  - [The effect of glutamine on the growth, metabolism and endostatin production of
      microencapsulated rCHO cells].
AB  - Cell transplantation is a promising technology in cancer therapy, however,
      immunological rejection is the major problem of cell transplantation. Based on
      the permselective property of microcapsule membrane, encapsulated cells can be
      immuno-protected. The normal physiological state and function expression of cells
      can be maintained so as to realize allo- or xenotransplantation. The
      microencapsulated cells grow in three dimensions, giving a more biologically
      representative in vivo model, which hints difference in characters of growth and
      metabolism compared to the monolayer cells. Therefore, characterization of growth
      and metabolism of microencapsulated recombinant CHO cells is essential for
      further large-scale culture. In present study, the effect of concentration of
      glutamine on the growth, metabolism and endostatin production of
      microencapsulated cells was investigated. In the experimental range of initial
      glutamine concentrations from 2.69mmol/L to 9.05mmol/L in the culture of
      microencapsulated recombinant CHO cells, the maximum density of active cells and
      multiplication ratios almost kept constant. The specific consumption rate of
      glucose increased with lower initial glutamine concentration (2.69mmol/L). When
      initial glutamine concentration was much higher (7.91mmol/L to approximately
      9.05mmol/L), the specific consumption rates of both glucose and glutamine
      increased while the efficiencies of glucose and glutamine decreased. The highest
      efficiencies of glucose and glutamine utilization were observed with initial
      glutamine concentration of 4.97mmol/L. It was also demonstrated that glutamine
      had significant effect on the accumulation of endostatin. The accumulative
      concentration of endostain reached its peak of 546.36 ng/mL with the initial
      glutamine concentration of 4.97mmol/L.

PMID- 16572859
TI  - [Application of microfluidic-chip in biomedicine].
AB  - As a novel analytical technology, the research of Micro total analysis systems
      (micro-TAS) has been spreading rapidly. micro-TAS has been widely used to perform
      chemical and biochemical analysis. Microfluidic-based analytical system as micro
      TAS's manily direction develops very fast in terms of it's reaction speed,
      reagent consumption, miniaturization, cost, and automation. After having proven
      the value of microfluidics for genetic, proteomic and cytomics analysis, this
      article also anticipates the development tendency of this technology in the
      biology medicine domain. It has demonstrated that a truly, easy-to-handle
      Microfluidic-based analytical device will be emerged in the future.

PMID- 16572860
TI  - QTc interval prolongation predicts postoperative mortality in heart failure
      patients undergoing surgical revascularization.
AB  - QTc interval prolongation is associated with increased mortality rates in
      patients with advanced heart failure. We investigated the predictive value of
      prolonged QTc interval in 567 patients with heart failure who were undergoing
      coronary artery bypass graft surgery The patients were in New York Heart
      Association class III or IV, with left ventricular ejection fractions of 0.40 or
      less. Before surgery, the QT interval duration was measured in leads II and V4 of
      the standard electrocardiogram and corrected by use of the Bazett formula. The
      QTc interval was prolonged (>440 msec) in 243 patients (43%) and normal in 324
      (57%). The 2 study groups--prolonged QTc versus normal QTc--did not differ in
      terms of age (62 +/- 11 years vs 64 +/- 10 years, P=0.65), sex (80% male vs 76%
      male, P=0.31), ejection fraction (0.29 +/- 0.08 vs 0.29 +/- 0.09, P=0.72),
      hypertension (82% vs 78%, P=0.34), or diabetes (11% vs 7%, P=0.10). Within 1
      month after coronary artery bypass grafting, 22 of 243 patients (9.1%) in the
      prolonged QTc group died, compared with 5 of 324 in the normal QTc group (1.5%)
      (P=0.0001). QTc interval prolongation was the only independent predictor of
      postoperative mortality on multivariate analysis (P=0.002). We conclude that
      patients with heart failure and preoperative QTc interval prolongation have
      increased mortality rates after coronary artery bypass grafting.

PMID- 16572861
TI  - Sharp dissection versus electrocautery for radial artery harvesting.
AB  - Radial arteries have been increasingly used during the last decade as conduits
      for coronary artery revascularization. Although various harvesting techniques
      have been described, there has been little comparative study of arterial damage
      and patency. A radial artery graft was used in 44 consecutive patients, who were
      randomly divided into 2 groups. In the 1st group, the radial artery was harvested
      by sharp dissection and in the 2nd, by electrocautery. These groups were compared
      with regard to radial artery free flow, harvest time, number of clips used,
      complications, and endothelial damage. Radial artery free flow before and after
      intraluminal administration of papaverine was significantly greater in the
      electrocautery group (84.3 +/- 50.7 mL/min and 109.7 +/- 68.5 mL/min) than in the
      sharp-dissection group (52.9 +/- 18.3 mL/min and 69.6 +/- 28.2 mL/ min)
      (P=0.003). Harvesting time by electrocautery was significantly shorter (25.4 +/-
      4.3 min vs 34.4 +/- 5.9 min) (P=0.0001). Electrocautery consumed an average of
      9.76 clips, versus 22.45 clips consumed by sharp dissection. The 2 groups were
      not different regarding postoperative complications, except for 3 cases of
      temporary paresthesia of the thumb in the electrocautery group; histopathologic
      examination found no endothelial damage. We conclude that radial artery
      harvesting by electrocautery is faster and more economical than harvesting by
      sharp dissection and is associated with better intraoperative flow and good
      preservation of endothelial integrity.

PMID- 16572862
TI  - In situ reconstruction with cryopreserved arterial allografts for management of
      mycotic aneurysms or aortic prosthetic graft infections: a multi-institutional
      experience.
AB  - We designed this study to evaluate a multi-institutional experience regarding the
      efficacy of cryopreserved aortic allografts in the treatment of infected aortic
      prosthetic grafts or mycotic aneurysms. We reviewed clinical data of all patients
      from 4 institutions who underwent in situ aortic reconstruction with
      cryopreserved allografts for either infected aortic prosthetic graft or mycotic
      aneurysms from during a 6-year period. Relevant clinical variables and treatment
      outcomes were analyzed. A total of 42 patients (37 men; overall mean age 63 +/-
      13 years, range 41-74 years) were identified during this study period. Treatment
      indications included 34 primary aortic graft infections (81%), 6 mycotic
      aneurysms (22%), and 2 aortoenteric erosions (5%). Transabdominal and
      thoracoabdominal approaches were used in 38 (90%) and 4 patients (10%),
      respectively. Staphylococcus aureus was the most commonly identified organism
      (n=27, 64%). Although there was no intraoperative death, the 30-day operative
      mortality was 17% (n=7). There were 21 (50%) nonfatal complications, including
      local wound infection (n=8), lower-extremity deep venous thrombosis (n=5),
      amputation (n=6), and renal failure requiring hemodialysis (n=2). The average
      length of hospital stay was 16.4 +/- 7 days. During a mean follow-up period of
      12.5 months, reoperation for allograft revision was necessary in 1 patient due to
      graft thrombosis (6%). The overall treatment mortality rate was 21% (n=9). In
      situ aortic reconstruction with cryopreserved allografts is an acceptable
      treatment method in patients with infected aortic prosthetic graft or mycotic
      aneurysms. Our study showed that mid-term graft-related complications such as
      reinfection or aneurysmal degeneration were uncommon.

PMID- 16572863
TI  - Biventricular pacing for heart failure patients on inotropic support: a review of
      38 consecutive cases.
AB  - Biventricular pacing (BiV) has documented benefit in New York Heart Association
      functional class III patients. Whether BiV offers benefit to class IV patients on
      inotropic therapy is unclear. Retrospective review was performed on 38
      consecutive heart failure patients who received BiV while on inotropic support or
      within 30 days of inotropic administration; the mean age was 63 +/- 13 yrs; 9
      were women. Fourteen who received inotropic agents did so in conjunction with
      coronary artery bypass grafting, or valve or infarct exclusion surgery. Twenty
      three patients received inotropic therapy only before BiV Nine other patients
      received inotropic therapy before BiV and at another point (5 at implant and 4
      after BiV); 6 were on inotropic support only at implant. Mean follow-up was 1.2
      +/- 0.9 years. There were 14 deaths. Survival estimates at 6 months, 1 year, and
      2 years were 74%, 71%, and 61%, respectively. When patients on inotropic therapy
      before BiV (n=32) were compared with patients never on such therapy before BiV
      (n=6), there was a survival difference (P <0.0001); all 6 patients not on
      inotropic therapy before BiV died within the first 2 years. Estimated 6-month and
      1-year survival for those on inotropic support before BiV was 84 % and 81 %,
      compared with 23% and 23% for the other group. Patients who required inotropic
      agents only before BiV fared better than those requiring inotropic support at
      other times. Although the patients in this survey were a very high-risk group, a
      small subset was weaned and had stable short-term survival.

PMID- 16572864
TI  - Left main coronary artery stenosis: factors predicting cardiac events in patients
      awaiting coronary surgery.
AB  - Although most patients with left main coronary artery stenosis undergo urgent
      coronary artery bypass grafting, limited information is available regarding the
      risk factors that might lead to cardiac events between angiographic diagnosis and
      surgery. We retrospectively reviewed 1,731 cases of coronary artery bypass
      grafting at our institution, 97 of which were performed in patients with
      significant (> or = 50%) left main coronary artery stenosis. These patients were
      placed in 1 of 2 groups: eventful waiting or uneventful waiting. We analyzed
      multiple preoperative variables, and the incidence of serious cardiac events
      (death, myocardial infarction, unstable angina, left ventricular failure, and
      life-threatening ventricular arrhythmias) during the waiting period between
      angiography and surgery Four patients (4.1%) experienced serious cardiac events
      while awaiting surgery (1 had non-ST-elevation myocardial infarction; 3 had life
      threatening ventricular arrhythmias); none died. All the events occurred more
      than 24 hours after cardiac catheterization. Of the preoperative variables
      analyzed (acute coronary syndrome, age, history of diabetes, hypertension,
      hyperlipidemia, smoking, renal failure, severity of left main stenosis, right
      coronary artery involvement, ejection fraction, and use of intra-aortic balloon
      pump), only acute coronary syndrome predicted the incidence of preoperative
      cardiac events (P=0.001). The occurrence of severe cardiac events while patients
      await coronary artery bypass grafting is rare. Carefully selected patients with
      severe left main coronary artery stenosis can safely await surgery. Concomitant
      acute coronary syndrome and severe left main coronary artery stenosis indicate a
      high risk for cardiac events. Therefore, in patients with these conditions,
      emergency coronary artery bypass may be preferable.

PMID- 16572865
TI  - Long-term follow-up of hearttransplant recipients with pre-transplant
      malignancies.
AB  - A pre-existing malignancy has disqualified patients from solid organ
      transplantation because of concerns regarding recurrence. We reviewed pre
      transplant characteristics and long-term results in patients who underwent heart
      transplantation with a pre-existing malignancy, because there has been no prior
      study of these patients in the long term. All 214 patients who underwent heart
      transplantation from July 1985 through June 2004 were studied retrospectively
      Thirteen of these patients had been treated for a malignancy before
      transplantation. Pre-transplant characteristics (age, sex, diabetes, and weight)
      and post-transplant outcomes (rejection, infection, and survival) were compared
      for the 2 groups. The patients with pre-existing malignancies were younger (47 vs
      54 years, P=0.014), less heavy (73 vs 79 kg, P=0.017), and more likely to be
      female (54% vs 22%, P=0.010), compared with recipients without a pre-malignancy.
      Pulmonary vascular resistances, histories of tobacco use, and incidence of pre
      transplant diabetes were not different between the 2 groups. The mean duration of
      follow-up for the 2 groups was similar (2,760 days for the pre-malignancy group
      vs 2,215 days for the non-pre-malignancy group, P=NS). Episodes of treated
      rejection and infection for the pre-malignancy group vs the non-pre-malignancy
      group were similar (1.8 episodes of rejection vs 1.6 episodes, P=NS); and (1. 7
      episodes of infection vs 0.8 episodes, P=0.098). None of the pre-malignancy
      patients had recurrence of their original cancer, and long-term survival for the
      2 groups was essentially identical (63% vs 62% at 10 years, P=NS). The
      dissemination of reports such as these may enable more patients with cured
      malignancies to benefit from transplantation.

PMID- 16572866
TI  - Traumatic brachial artery injuries.
AB  - We performed this retrospective study to analyze our strategies for managing and
      surgically treating brachial artery injuries. Fifty-seven patients with a total
      of 58 traumatic brachial artery injuries underwent surgery at our institution,
      from August 1996 through November 2004. Fifty-four patients were male and 3 were
      female (age range, 7 to 75 years; mean, 29.4 years). Forty-four of the patients
      had penetrating injuries (18 had stab wounds; 16, window glass injuries; and 10,
      industrial accidents), 10 had blunt trauma injuries (traffic accidents), and 3
      had gunshot injuries. Fourteen patients (24.6%) had peripheral nerve injury. All
      patients underwent Doppler ultrasonographic examination. The repair of the 58
      arterial injuries involved end-to-end anastomosis for 32 injuries (55.2%),
      reverse saphenous vein graft interpositional grafts for 18 (31%), and primary
      repair for 8 (13.8%). Venous continuity was achieved in 11 (84.6%) of 13 patients
      who had major venous injuries. Nine of the 57 patients (15.8%) required primary
      fasciotomy. Follow-up showed that 5 of the 14 patients with peripheral nerve
      injury had apparent disabilities due to nerve injury. One patient underwent
      amputation. There were no deaths. We believe that good results can be achieved in
      patients with brachial artery injuries by use of careful physical examination,
      Doppler ultrasonography, and restoration of viability with vascular repair and
      debridement of nonviable tissues. Traumatic neurologic injury frequently leads to
      disability of the extremities.

PMID- 16572867
TI  - Effect of myocardial reperfusion on the release of nitric oxide after regional
      ischemia: an experimental model of beating-heart surgery.
AB  - Off-pump coronary artery bypass surgery is increasing in popularity worldwide.
      However, very little is known about the effect of regional myocardial ischemia
      reperfusion on nitric oxide release. In an animal model mimicking off-pump
      bypass, male Sprague-Dawley rats (350-450 g) were mechanically ventilated under
      general anesthesia. After left lateral thoracotomy, the animals underwent
      occlusion of either the left anterior descending artery (for 3, 5, 75, 10, 12.5,
      15, or 20 minutes) or the circumflex artery (for 5, 10, or 15 minutes). Twenty
      four hours after reperfusion, heart tissue was stained for determination of the
      area at risk and the infarcted area. Blood samples obtained before ischemia, 10
      minutes after reperfusion, and 24 hours after reperfusion were analyzed for
      plasma concentrations of nitric oxide. After occlusion of the left anterior
      descending artery, the size of the infarcted area increased dramatically as the
      duration of occlusion increased, and was significantly larger after 12.5, 15, or
      20 minutes of occlusion than after 3 minutes. After occlusion of the circumflex
      artery, the size of the infarcted area increased steadily and was significantly
      larger after 15 minutes of occlusion than after 5 minutes. There was no
      significant correlation between the duration of coronary occlusion and the plasma
      concentration of nitric oxide: 10 minutes after reperfusion, this concentration
      was significantly lower than that before ischemia, but it was twice the baseline
      level 24 hours after reperfusion. We concluded that the duration of regional
      ischemia did not affect the plasma concentration of nitric oxide in the systemic
      circulation.

PMID- 16572868
TI  - Hyperkalemia revisited.
AB  - Hyperkalemia is a common clinical condition that can induce deadly cardiac
      arrhythmias. Electrocardiographic manifestations of hyperkalemia vary from the
      classic sine-wave rhythm, which occurs in severe hyperkalemia, to nonspecific
      repolarization abnormalities seen with mild elevations of serum potassium. We
      present a case of hyperkalemia, initially diagnosed as ventricular tachycardia,
      to demonstrate how difficult hyperkalemia can be to diagnose. An in-depth review
      of hyperkalemia is presented, examining the electrophysiologic and
      electrocardiographic changes that occur as serum potassium levels increase. The
      treatment for hyperkalemia is then discussed, with an emphasis on the mechanisms
      by which each intervention lowers serum potassium levels. An extensive literature
      review has been performed to present a comprehensive review of the causes and
      treatment of hyperkalemia.

PMID- 16572869
TI  - Off-pump insertion of an extracorporeal LVAD through a left upper-quadrant
      incision.
AB  - Insertion of an extracorporeal left ventricular assist device for temporary
      ventricular support via median sternotomy can be challenging in patients with a
      history of cardiac surgery, because these patients often poorly tolerate the
      lengthy dissection and cardiac manipulation necessary for exposure of the left
      ventricular apex and ascending aorta. Our approach, transdiaphragmatic left
      ventricular inflow cannulation with return through a graft sewn to the
      supraceliac aorta, can be accomplished through a left upper-quadrant abdominal
      incision without entering the peritoneal cavity, mediastinum, or left hemithorax.
      Repeated sternotomy and mediastinal dissection are thus avoided. To our
      knowledge, this report documents the 1st use of this technique for insertion of
      an extracorporeal pulsatile ventricular assist device for temporary ventricular
      support.

PMID- 16572870
TI  - Large left atrial myxoma with severe mitral regurgitation: the inverted T-shaped
      biatrial incision revisited.
AB  - Cardiac myxomas are primary cardiac tumors. In some cases of atrial myxoma, the
      standard left atriotomy alone does not enable safe tumor resection and easy
      access to the mitral valve. We report the cases of 2 patients with huge left
      atrial myxomas associated with severe mitral valve regurgitation who underwent an
      inverted T-shaped biatrial incision for tumor excision and mitral repair. This
      approach reduces tumor fragmentation and permits good mitral valve exposure.

PMID- 16572871
TI  - Detachment of the mitral valve anterior leaflet as a complication of aortic valve
      replacement.
AB  - Mitral regurgitation after aortic valve replacement is generally reported as a
      complication of a Manouguian's procedure for annulus enlargement. However, even
      if no annular enlargement procedure is performed, this complication may be
      encountered after isolated aortic valve replacement because of either extensive
      decalcification of the aortic annulus or progressive tension on the anterior
      leaflet of the mitral valve, caused by aortic valve sutures placed adjacent to
      firm or heavily calcified valve tissue. Routine transthoracic echocardiography
      may be inadequate for diagnosis of this condition; transesophageal
      echocardiography should be used both for preoperative diagnosis and for
      intraoperative management. We report the case of a patient who had severe mitral
      regurgitation that occurred after aortic valve replacement with a mechanical
      valve.

PMID- 16572872
TI  - Guillain-Barre syndrome as a cause of reversible cardiomyopathy.
AB  - Although autonomic dysfunction is a common manifestation of Guillain-Barre
      syndrome, cardiovascular involvement in this setting has rarely been reported in
      the literature. We describe a case of reversible left ventricular systolic
      dysfunction in a 60-year-old man with Guillain-Barre syndrome. Our patient had no
      history or signs of cardiac dysfunction on initial presentation. During the
      clinical manifestation of his autonomic dysfunction, he developed
      electrocardiographic changes accompanied by mildly elevated cardiac enzymes and
      severe left ventricular systolic dysfunction and segmental wall motion
      abnormality, which coincided with elevated urinary catecholamine and
      vanilmandelic acid levels. These abnormalities, and his symptoms, resolved
      rapidly once the acute episode was over. We believe the reversible left
      ventricular dysfunction was due to the toxic effect of increased catecholamines
      and to the transiently damaged sympathetic nerve endings in the myocardium,
      presumably a consequence of Guillain-Barre syndrome. We recommend that
      echocardiography be performed in patients with clinical signs of autonomic
      dysfunction, especially if they are associated with abnormal electrocardiographic
      findings, cardiac enzyme elevation, or hemodynamic instability, so that
      appropriate medical therapy can be instituted in a timely manner.

PMID- 16572873
TI  - Late manifestation of a large congenital tracheoesophageal fistula in an adult.
AB  - Congenital tracheoesophageal fistula in an adult is a rare condition. We describe
      the clinical presentation in a young woman after video-assisted thoracoscopic
      pleurodesis for spontaneous pneumothorax. She was found to have a very wide and
      short fistula in her neck. The tracheoesophageal defect was closed by a trap-door
      flap, using the posterior wall of the trachea. The patient made an uncomplicated
      recovery.

PMID- 16572874
TI  - Papillary fibroelastoma presenting as left ventricular mass.
AB  - A 38-year-old woman presented with chest pain. Two-dimensional echocardiography
      revealed a mobile mass in the left ventricle, attached to the posterior papillary
      muscle of the mitral valve without valvular involvement. The tumor was resected.
      Histopathology confirmed the tumor as papillary fibroelastoma. Our case
      highlights an atypical presentation of papillary fibroelastoma.

PMID- 16572875
TI  - Ruptured sinus of valsalva aneurysm in a pregnant woman.
AB  - A ruptured sinus of Valsalva aneurysm is a rare cardiac anomaly, usually of a
      congenital nature. There are few documented cases of this condition during
      pregnancy, which renders unclear the therapeutic options. We report the case of a
      35-year-old pregnant woman who presented at the hospital for cardiac evaluation
      due to the presence of a heart murmur. The patient was asymptomatic and in her
      4th month of pregnancy. Transthoracic echocardiography revealed a ruptured sinus
      of Valsalva aneurysm and a fistula to the right ventricle with evidence of a
      continuous left-to-right shunt.

PMID- 16572876
TI  - Aortic root dilatation with sinus of valsalva and coronary artery aneurysms
      associated with ankylosing spondylitis.
AB  - The HLA-B27-related spondyloarthopathies are associated with cardiovascular
      disease in 2% to 10% of cases. Inflammation and sclerosis of the aortic root and
      ventricular septum have been linked to the development of isolated aortic
      regurgitation and conduction abnormalities; however, aneurysms of the aortic
      sinuses and coronary arteries have not been previously described. We report the
      case of a 58-year-old white man who presented for evaluation of dyspnea and was
      found to have aneurysms of the sinuses of Valsalva and the circumflex coronary
      artery. The patient underwent aortic root replacement. Approximately 3 months
      later, he presented with symptoms, radiographs, and laboratory data consistent
      with ankylosing spondylitis. To our knowledge, these particular cardiovascular
      manifestations of HLA-B27-related disease have not been previously reported. This
      case expands the clinical spectrum of the disease and should prompt the clinician
      to consider the possibility of HLA-B27-associated cardiovascular disease in
      patients who have aortic and coronary aneurysms.

PMID- 16572877
TI  - Acute spinal cord ischemia during aortography treated with intravenous
      thrombolytic therapy.
AB  - Acute anterior spinal cord ischemia is a rare but disastrous complication of
      endovascular aortic procedures. Although intravenous thrombolysis with
      recombinant tissue plasminogen activator is an effective treatment for acute
      brain ischemia, its use for the treatment of spinal cord ischemia has not
      previously been reported. We report the case of a patient who developed anterior
      spinal cord ischemia during diagnostic aortography He was treated with
      intravenous recombinant tissue plasminogen activator within 3 hours after the
      onset of symptoms. The patient had a rapid neurologic improvement and was
      discharged from the hospital 3 days after thrombolysis, regaining his ability to
      walk unassisted. We propose that acute spinal cord ischemia can be treated with
      intravenous recombinant tissue plasminogen activator within 3 hours after the
      onset of symptoms, as can any other case of acute ischemic stroke.

PMID- 16572878
TI  - Paradoxical and pulmonary embolism due to a thrombus entrapped in a patent
      foramen ovale.
AB  - A 70-year-old woman, with a history of recent thromboembolic stroke, was admitted
      to our hospital because of sudden dyspnea due to pulmonary thromboembolism.
      Transthoracic echocardiography revealed a tubular thrombus entrapped in a patent
      foramen ovale. Transesophageal echocardiography confirmed this finding and also
      revealed an atrial septal aneurysm. Because her cerebral status contraindicated
      surgical intervention, medical therapy with heparin and warfarin was started.
      Follow-up transthoracic echocardiography, performed 3 weeks after the initiation
      of therapy, revealed complete resolution of the thrombus. Medical therapy can be
      an alternative to surgical therapy in high-risk patients who have entrapped
      thrombi.

PMID- 16572879
TI  - Traumatic common carotid-jugular fistula: report of 2 cases.
AB  - Traumatic common carotid artery-to-internal jugular vein fistula is a rare entity
      that is not usually detected during the acute injury phase. We present 2 cases of
      traumatic carotid-jugular fistula. Both involved the right side of the neck, and
      both were due to injury from a firearm. The patients exhibited signs of high
      cardiac output. In Patient 1, the diagnosis was made by clinical examination and
      radiography. After diagnosis, the patient's parents requested his discharge from
      the hospital because of an inability to pay for treatment. The patient did not
      return. Patient 2 had a brachial plexus injury in addition to a carotid-jugular
      fistula. Diagnosis of the fistula was confirmed by color-flow echo Doppler
      scanning. Treatment consisted of division of the fistula and direct suture
      repair. The surgery required cross-clamping of the common carotid artery for 25
      minutes; nonetheless, the patient recovered without cerebral ischemia. Carotid
      jugular fistula should always be treated early to avoid the complications
      associated with the injury.

PMID- 16572880
TI  - Perioperative myocardial infarction secondary to dynamic circumflex coronary
      artery occlusion after mitral valve repair.
AB  - Few reported cases document injury to the circumflex coronary artery secondary to
      repair of the mitral valve annulus. This potentially life-threatening sequela
      must be considered during mitral valve repair. In an effort to increase awareness
      of this sequela, we present the case of a patient who experienced a perioperative
      myocardial infarction secondary to injury of the circumflex coronary artery after
      mitral valve repair.

PMID- 16572881
TI  - Cardiac fibroma as an inherited manifestation of nevoid basal-cell carcinoma
      syndrome.
AB  - We report the case of an 8-month-old male infant presenting with life-threatening
      ventricular tachycardia. Echocardiography revealed a left ventricular tumor. The
      tumor was resected through a left ventriculotomy, and the left ventricle was
      reconstructed after a partial ventriculectomy Histologic investigation showed a
      completely resected benign fibroma. The 30-year-old mother was known to have
      nevoid basal-cell carcinoma syndrome, which can be associated with cardiac
      fibromas. We believe that this is an interesting addition to the medical
      literature.

PMID- 16572882
TI  - Spontaneous hemopneumothorax as a result of venous hemangioma: a unique case?
AB  - Spontaneous hemopneumothorax is a rare clinical entity that can be life
      threatening, with a significant increase in mortality if not recognized and
      treated in time. We report the case of a young man who presented to us with
      nontraumatic spontaneous hemopneumothorax. Histologic examination of lung tissue
      showed the most likely cause of the bleeding to be venous hemangioma, which to
      the best of our knowledge has not been reported before.

PMID- 16572883
TI  - Asymptomatic incomplete left ventricular apical rupture diagnosed by cardiac
      magnetic resonance imaging.

PMID- 16572884
TI  - Supracristal ventricular septal defect.

PMID- 16572885
TI  - Vineberg procedure for inadvertent injury to anomalous left anterior descending
      artery during tetralogy of fallot repair: four decades later.

PMID- 16572886
TI  - Mitral valve endocarditis presenting as complete heart block.

PMID- 16572887
TI  - Cutaneous adverse events and gemifloxacin: observations from the clinical trial
      program.
AB  - Cutaneous adverse events are seen with many antimicrobials. A signal was observed
      with gemifloxacin in the original clinical research program, however subsequent
      studies and analysis demonstrated a mild-moderate self-limited macular-papular
      rash seen most frequently when the duration of exposure was beyond 7 days, a non
      approved duration. Following administration for 5 days for community-acquired
      respiratory tract infections the rash rate is typically less than 1.5%, a rate
      similar to that for other fluoroquinolones and lower than other frequently used
      community antimicrobials. The rash associated with gemifloxacin has not been
      linked with cross or subclinical-sensitization nor any systemic manifestations
      such as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis. This review
      describes the extensive studies conducted to support the use of this agent for
      short durations in community infections.

PMID- 16572888
TI  - Antibiotic susceptibility tests directly on urine samples using Uro-Quick, a
      rapid automated system.
AB  - During the period June 2003-March 2004, 12,579 urine samples were examined
      employing the Uro-Quick system. Positive samples (1,948) were subsequently Gram
      stained and processed by standard procedures for microorganism identification and
      antibiotic susceptibility determination by the disk diffusion method. Results of
      this latter test were compared with those obtained employing the new rapid Uro
      Quick method. Antibiotics were introduced in vials containing 2 ml of Mueller
      Hinton broth, then 0.5 ml of urine or a bacterial suspension in broth were added;
      a vial without drug was used as control. After 3 and 5 hours of incubation (for
      Gram-negative and Gram-positive strains respectively) the instrument showed the
      results. No growth and a growth curve like the control indicated susceptible and
      resistant strains respectively. Overall 1,590 Gram-negative strains were tested
      against ciprofloxacin, nitrofurantoin, amoxicillin-clavulanate, ceftazidime,
      fosfomycin, imipenem, amikacin, trimethoprim-sulfamethoxazole, and piperacillin
      tazobactam, while 358 Gram-positive bacteria were assessed against ciprofloxacin,
      nitrofurantoin, amoxicillin-clavulanate, ampicillin, fosfomycin, gentamicin,
      oxacillin and trimethoprim-sulfamethoxazole. Against the major urinary tract
      pathogens (Escherichia. coli, enterococci, Klebsiella spp. and Proteus spp.)
      agreement between the Uro-Quick system and the disk diffusion test generally was
      >90% for all antibiotics tested. On the basis of these results the system appears
      useful not only for bacteriuria screening, but also to rapidly test the
      antibiotic susceptibility of common uropathogens.

PMID- 16572889
TI  - Antibiotic resistance and mechanisms implicated in clinical enterococci in a
      Tunisian hospital.
AB  - Susceptibility testing for 15 antibiotics was performed in a series of 191
      clinical enterococci recovered in a Tunisian Hospital during 2000-2003. Species
      detected were the following ones (number of isolates): E. faecalis (139), E.
      faecium (41), E. casseliflavus (5), E. gallinarum (3), E. avium (2) and E. hirae
      (1). The percentages of antibiotic resistance detected were as follows (E.
      faecalis/ E. faecium/ other species) : penicillin (0/ 73/ 9%), tetracycline (78/
      44/ 54%), chloramphenicol (52/ 29/ 27%), erythromycin (66/ 100/ 82%), spiramycin
      (84/ 83/ 64%), pristinamycin (100/ 0/ 73%), trimethoprim-sulfamethoxazole (88/
      78/ 91%), rifampicin (72/ 41/ 0%), vancomycin (0/ 0/ 36%), teicoplanin (0/ 0/
      0%), high-level-resistance for gentamicin (24/ 29/ 45%), streptomycin (34/ 56/
      55%) and kanamycin (41/ 68/ 55%). Increased vancomycin minimum inhibitory
      concentrations (MICs) were only detected in E. casseliflavus and E. gallinarum
      isolates (MIC range 8-24 microg/ml). The erm(B), catA, tet(M), aac(6')-aph(2''),
      aph(3')-IIIa, and ant(6)-Ia genes were detected in 91%, 32%, 86%, 98%, 100%, and
      72% of the E. faecium and E. faecalis isolates resistant to erythromycin,
      chloramphenicol, tetracycline and high-level-resistant to gentamicin, kanamycin
      and streptomycin, respectively. A total of 20 unrelated pulsed-field-gel
      electrophoresis patterns were found in the series of 46 high-level gentamicin
      resistant E. faecalis and E. faecium isolates of this study.

PMID- 16572890
TI  - In vitro activity of daptomycin alone and in combination with various
      antimicrobials against Gram-positive cocci.
AB  - The increasing prevalence of resistant Gram-positive cocci requires the need to
      search for more effective agents and synergistic combinations. Forty-two
      vancomycin-resistant Enterococcus faecium (VREF), 30 methicillin-resistant
      Staphylococcus aureus (MRSA) and 36 Staphylococcus epidermidis (MRSE) strains
      were studied. Minimum inhibitory concentrations (MICs) were determined and
      synergy testing was performed by using E test for daptomycin, ampicillin
      sulbactam, piperacillin-tazobactam and ticarcillin-clavulanate against
      staphylococci; for daptomycin, ampicillin, rifampin, and gentamicin against
      enterococci. Daptomycin in combination with ampicillin, rifampin, and gentamicin
      was tested against enterococci; daptomycin in combination with ampicillin
      sulbactam, piperacillin-tazobactam, and ticarcillin-clavulanate was tested
      against staphylococci. Interaction categories were defined by the fractional
      inhibitory concentration (FIC) index. All strains of staphylococci and
      enterococci were susceptible to daptomycin. All three combinations showed synergy
      against more than 70% of the MRSA strains. Daptomycin in combination with
      ampicillin, rifampin, and gentamicin against enterococci showed synergies of
      64.2%, 57.1% and 21.4%, respectively. This study indicates that daptomycin alone
      and combined with beta-lactams seems to be effective against MRSA, but further in
      vitro and in vivo studies on the subject are required before clinical use can be
      recommended.

PMID- 16572891
TI  - Clinical efficacy and tolerability of levofloxacin in patients with liver
      disease: a prospective, non comparative, observational study.
AB  - The aim of this open, non comparative, observational study was to assess the
      clinical and bacteriological efficacy, the tolerability and safety of
      levofloxacin for treatment of concurrent bacterial infections in patients with
      chronic liver disease. Overall, 40 patients (inpatients or outpatients) were
      recruited to the study (28 with UTI, 6 with pneumonia, and 6 with spontaneous
      bacterial peritonitis (SBP)). Patients affected by UTI received 250 mg oral
      levofloxacin once daily for five days; patients with pneumonia or SBP underwent a
      10/14-day therapeutic oral regimen with 500 mg b.i.d. Clinical evaluation and
      possible side effects were monitored daily both in out- and in-patients. For all
      patients, laboratory tests were performed at baseline and 3-4 days after the end
      of therapy in order to evaluate levofloxacin tolerability. Statistical analysis
      was performed by means of Student's t test to show differences between cases; all
      values are reported as means and standard deviations and p values were considered
      as significant when p<0.05. After treatment, clinical cure and bacteriological
      eradication were achieved in all patients (40/40; 100%). Adverse events, mainly
      gastrointestinal disturbances (e.g. nausea), were observed in 5 out of 40
      patients (12.5%) and no neurotoxic effects were registered (e.g. anxiety,
      hallucinations, convulsions, mental confusion). No significant variation in
      laboratory tests due to hematic crasis and/or hepatic and renal disorders was
      observed. Levofloxacin proved to be highly efficacious and safe in the treatment
      of bacterial infections in patients affected by liver disease.

PMID- 16572892
TI  - Antibiotic prophylaxis for surgical procedures on children.
AB  - The aim of this study was to evaluate adherence to current local antimicrobial
      prophylaxis guidelines for children requiring different surgical procedures. One
      hundred and fifty consecutive surgical procedures on children were included in
      this retrospective study of adherence. The indication, choice of antibiotic,
      timing, dose, duration and dosing interval were evaluated and found to be
      concordant with present local guidelines in 97.3%, 83.3%, 66%, 92%, 40.7% and
      94.1% of cases, respectively. Adherence to all parameters was achieved in only
      25.3% of cases. Although the overall adherence to antibiotic prophylaxis
      guidelines was relatively low, the majority of children (84.6%) received an
      appropriate antibiotic (90.6%) at the appropriate dose (92%) and at appropriate
      intervals (94.1%). The most discordant duration of prophylaxis was due to
      controversies in urological prophylaxis guidelines.

PMID- 16572893
TI  - Extended lamivudine treatment in patients affected by chronic active anti-Hbe
      positive hepatitis.
AB  - The aim of the study was to evaluate the biochemical and virological response and
      the histological changes in 34 chronic hepatitis B anti-Hbe-positive patients
      treated with lamivudine at 100 mg/day orally for five years. Liver biopsies were
      performed in all patients at least 6 months before starting therapy and 3 months
      after the stop of treatment. After 12 months of therapy, 70.6% of patients showed
      evidence of HBV DNA clearance and normal ALT levels; 64.7% and 55.8% of patients
      maintained a complete response after two and three years of therapy,
      respectively, 47% after four years and 44.1% after five years. The histological
      activity index improved in 13%, remained unchanged in 61% and worsened in 26% of
      patients with tyrosine-methionine-aspartate-aspartate (YMDD) variants compared to
      63, 27 and 0% without variants, respectively. The authors conclude that the
      clinical benefit of lamivudine is greatest for patients without YMDD variants
      after 5 years of extended treatment.

PMID- 16572894
TI  - An in vitro study of the cytogenetic and cytotoxic effects of imatinib mesylate,
      STI571 on murine erythroleukemia GM-86 cells.
AB  - Imatinib mesylate, STI571, is a novel anticancer drug used to treat Philadelphia
      chromosome positive (Ph+) chronic myeloid leukemia. Studies have demonstrated the
      efficacy of imatinib mesylate in human cancers; however, its effects in murine
      cancer cell lines are not well documented. This study investigated the
      cytogenetic and cytotoxic effects of imatinib mesylate in vitro on virus-induced
      mouse erythroleukemia GM-86 cells. Cytogenetic studies revealed a noticeable
      increase in chromosomal abnormalities and multinucleation, as well as micro and
      macronuclei formation in treated cells. An increase in abnormalities such as
      condensed nuclei and nuclear and cytoplasmic degradations were also detected in
      cells treated with imatinib mesylate. It is suggested that the reduction in cell
      proliferation, mitotic index, and increase in cell damaging effects observed in
      imatinib mesylate-treated GM-86 cells were a result of the induced chromosomal
      and nuclear abnormalities.

PMID- 16572895
TI  - Modulation of vascular endothelium by imatinib: a study on the EA.hy 926
      endothelial cell line.
AB  - In this study the EA.hy 926 endothelial cell line--simulating endothelial cells-
      was treated with imatinib in order to define a possible anti-angiogenic role for
      imatinib. Dose and time response experiments were performed. Cell morphology was
      studied, while migration efficiency, intercellular permeability and VE-cadherin
      expression were assayed, both in the presence and in the absence of imatinib.
      Imatinib-induced EA.hy 926 cell apoptosis was also examined. Results showed that
      imatinib reduced the endothelial cell population, changed cell monolayer
      morphology and reduced cell-to-cell cohesiveness. Migration efficiency was
      significantly decreased while intercellular permeability was 2.76-fold increased
      in the presence of imatinib. Indirect immunofluorescence microscopy showed nearly
      complete down-regulation of VE cadherin in imatinib-treated cells. Furthermore,
      apoptotic activity was detected in imatinib-treated cells. Altogether our results
      support an antiangiogenic profile for imatinib that possibly contributes to its
      therapeutic potential.

PMID- 16572896
TI  - Induced resistance in the human non small cell lung carcinoma (NCI-H460) cell
      line in vitro by anticancer drugs.
AB  - Exposure of human non-small cell lung cancer cells (NCI-H460) to gradually
      increasing concentrations of doxorubicin resulted in the appearance of a new cell
      line (NCI-H460/R) that was resistant to doxorubicin (96.2-fold) and cross
      resistant to etoposide, paclitaxel, vinblastine and epirubicin. Slight cross
      resistance to two MDR-unrelated drugs 8-Cl-cAMP and sulfinosine was observed.
      Flow cytometry analysis showed that the accumulation of doxorubicin in the
      resistant cells was 88.4% lower than in the parental cells. Also, verapamil
      significantly decreased the efflux rate in NCI-H460 and NCI-H460/R cells, whereas
      curcumin inhibited the efflux in NCI-H460 cells only. Gene expression data
      confirmed the induction of mdr1 (P-gp), as judged by the observed 15-fold
      increase in its mRNA concentration in doxorubicin-resistant NCI-H460/R cells. In
      contrast, mrp1 and lrp expression was unaffected by the doxorubicin resistance.
      Further work should develop a rationale for a novel treatment of NSCLC with
      appropriate modulators of resistance aimed at improving the outcome of the
      acquired drug resistance.

PMID- 16572897
TI  - P53, COX-2, iNOS protein expression changes and their relationship with anti
      oxidant enzymes in surgically and multi-modality treated esophageal carcinoma
      patients.
AB  - Esophageal carcinoma has a high incidence in India but its etiology remains
      unknown. In the present study the correlation between apoptosis regulatory
      proteins and anti-oxidant enzymes in 40 esophageal carcinoma patients was
      examined. Patients in one group were operated by transhiatal esophagectomy and in
      the second group were administered cisplatin (30 mg/m2/day) and 5-fluorouracil (5
      FU) (750 mg/m2/day) daily for three days followed by surgery after four weeks of
      neo-adjuvant therapy (NAT). Complete pathological response was achieved in 15% of
      patients. Results obtained by Western blot analysis showed over-expressed p53 and
      COX-2 protein levels in the tumor tissues as compared to the adjoining tissue and
      its paired normal mucosa in both groups of patients. Immunohistochemical studies
      showed heterogenous p53 staining pattern with sections showing both nuclear and
      cytoplasmic staining with 36.8% mild, 10.5% moderate and 52.6% intense p53
      immunoreactivity. Both COX-2 and iNOS immunostaining revealed 25% negative and
      75% mild to strongly positive immunoreactivity. Correlation studies demonstrated
      a positive relationship between p53 and COX-2 (P=0.030; r = +0.70) in surgically
      treated patients. The association of COX-2 and p53 with various anti-oxidant
      enzymes showed a significantly positive correlation between COX-2 expression and
      catalase activity and an inverse correlation between p53 expression and
      superoxide dismutase and catalase activity in the tumor tissue of patients given
      NAT. In addition, we observed a negative trend between p53 expression levels and
      GPx enzyme levels in both the adjoining and tumor tissue of patients having
      undergone surgery as main mode of treatment.

PMID- 16572898
TI  - Capecitabine chemoradiation for rectal cancer after curative surgery.
AB  - This study reports the tolerability and feasibility of capecitabine, an oral
      fluoropyrimidine, chemoradiation as postoperative treatment. Stage II-III rectal
      cancer patients received 2 cycles of bolus 5-FU (425 mg/m2) and leucovorin (LV)
      (20 mg/m2) on days 1-5 q3w followed by oral capecitabine (800 mg/m2 bid)
      continuously during pelvic radiotherapy (total 50.4 Gy). Two additional cycles of
      5-FU/LV were finally administered. Forty-one radically resected patients (median
      age: 61 years) were enrolled. All patients were evaluable for safety. Grade 3
      adverse events included: proctitis (n = 3, 7%), diarrhea (n = 5, 12%), and
      leukopenia (n = 1, 2%). The overall rate of grade 3 diarrhea and leukopenia was
      15% (95% confidence interval, 5-29%). Capecitabine chemoradiation in the adjuvant
      setting is well tolerated and is convenient to administer. These results support
      the use and further study of capecitabine chemoradiation in radically resected
      rectal cancer patients.

PMID- 16572899
TI  - Concurrent radiotherapy does not affect adjuvant CMF delivery but is associated
      with increased toxicity in women with early breast cancer.
AB  - We evaluated whether concurrent radiotherapy (RT) affected delivery and toxicity
      of adjuvant intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil)
      in women with operable breast cancer. The medical charts of 321 consecutive
      breast cancer patients who received CMF either alone for 6 cycles, or for 4
      cycles following of an anthracycline (A-CMF) were reviewed. One hundred forty
      four women underwent radiotherapy concurrently with CMF. Optimal CMF delivery
      (success as opposite to failure) was defined as the combined achievement of an
      average relative dose intensity (aRDI) > or = 85% and an average percent of the
      total dose (aPTD) > or = 90% for the three drugs in the CMF regimen. Multivariate
      logistic regression analysis showed that concurrent-RT did not affect CMF
      delivery (OR for success 1.391 p=0.230). The sequential A-CMF regimen (OR for
      success 0.208, 95% C.I. 0.120-0.360, p<0.001) and age > or = 56 (OR for success
      0.351, 95% C.I. 0.200-0.161, p<0.001) were independently associated with
      suboptimal CMF delivery. Moreover, concurrent RT was independently associated
      with increased leukopenia, thrombocytopenia, upper abdominal pain, mucositis and
      fatigue. Our retrospective analysis suggests that concurrent-RT has no impact on
      optimal CMF delivery, but it increases the burden of CMF-related toxicity.

PMID- 16572900
TI  - Chemosensitization effects of XIAP downregulation in K562 leukemia cells.
AB  - The effect of downregulation of the expression of the antiapoptotic protein XIAP
      with antisense oligonucleotides was evaluated in the K562 chronic myeloid
      leukemia (CML) cell line. This was carried out by studying the effects of
      downregulation of XIAP expression on cellular viability, cellular apoptosis and
      on the response to two chemotherapeutical drugs, etoposide and doxorubicin. We
      document that downregulation of XIAP expression decreased cellular viability,
      increased cellular apoptosis and enhanced the effects of doxorubicin.

PMID- 16572901
TI  - Chronic peripheral arteriopathy is associated with seropositivity to Chlamydia
      pneumoniae.
AB  - The study was carried out to clarify the correlation between Chlamydia pneumoniae
      infection and peripheral arterial disease (PAD). The level of specific antibodies
      of the 133 consecutive patients suffering from PAD at 2nd stage of Leriche's
      classification were compared with 60 healthy controls by using a commercial Micro
      IF Test. A higher incidence of serological evidence of C. pneumoniae infection
      was found in the patients (106/133) than in controls (6/60). These results are in
      agreement with other findings that measured the infection in atheromasic plaques.
      A strong cause-effect relationship between bacterial infection and peripheral
      arterial disease was not found, but the raised seropositivity level could be
      considered as a target for medical therapy of PAD.

PMID- 16572902
TI  - The inhibitory effect of antihyperlipidemic drugs on the growth of Chlamydia
      pneumoniae in vitro.

PMID- 16572903
TI  - Enterobacter cloacae in an Italian Neonatal Intensive Care Unit: pattern of drug
      resistance compared with an international database (SENTRY Antimicrobial
      Surveillance Program).

PMID- 16572904
TI  - Tetracycline resistant plasmids from uropathogenic Escherichia coli from
      Southwestern Nigeria.

PMID- 16572905
TI  - Azithromycin: 1.0 or 3.0 gram dose in the treatment of patients with asymptomatic
      urogenital chlamydial infections.

PMID- 16572906
TI  - Surgery for vaginal prolapse: a review.
AB  - This article reviews clinical trials of surgery for the repair of apical vaginal
      prolapse. The procedures include those from the abdominal, laparoscopic and
      transvaginal approach. When considering new surgical devices or procedures, it is
      essential to be aware of clinical data. The use of tension-free tape devices for
      apical support is promising, but a large trial is needed to demonstrate its
      efficacy and safety.

PMID- 16572907
TI  - Vaginal hysterectomies performed in a residency program: can we increase the
      number?
AB  - OBJECTIVE: To evaluate if a concerted effort to increase the number of vaginal
      hysterectomies performed in a residency program could be accomplished safely when
      a standard approach vs. a concerted effort was utilized. STUDY DESIGN: A
      retrospective case review was performed for all patients undergoing vaginal
      hysterectomy at 1 hospital in a residency program. At Denver Health Medical
      Center, the Gynecology Division made a concerted effort to increase the number of
      vaginal hysterectomies performed. All hysterectomies from July 1998 to December
      2003 were reviewed retrospectively. Abstracted data included age, race, parity,
      primary diagnosis, past medical history, past surgical history, history of pelvic
      inflammatory disease/sexually transmitted disease, removal of ovaries, conversion
      to an abdominal procedure, complications, length of hospital stay, and change in
      hematocrit. RESULTS: Over 1,029 hysterectomies were performed during the study
      period. In the first 3 years, 190 vaginal hysterectomies were performed. During
      the second 3 years, 320 hysterectomies were performed vaginally; laparoscopic
      vaginal hysterectomies were excluded. The percentage of vaginal hysterectomies
      performed increased from 37% to 60%. Age, race, uterine weight, primary diagnosis
      and past medial history were not significantly different (p>0.05). A significant
      difference was noted during the second period with regard to parity, previous
      surgeries, history of sexually transmitted diseases, removal of ovaries, length
      of hospital stay and complication rate. CONCLUSION: When there is a concerted
      effort to perform vaginal hysterectomies in lieu of abdominal ones in a residency
      program, the number can increase without increasing the complication rate.

PMID- 16572908
TI  - Predictors of methotrexate treatment failure in ectopic pregnancy.
AB  - OBJECTIVE: To determine the possible predictors of methotrexate treatment failure
      in ectopic pregnancy. STUDY DESIGN: Fifty-eight patients diagnosed with ectopic
      pregnancy were treated with methotrexate (50 mg/m2). Selected variables in the
      history of the patients, the signs and symptoms at the time of admission,
      transvaginal ultrasound findings and serum beta-human chorionic gonadotropin
      (beta-hCG) levels on day 1 and 3 were evaluated in a logistic regression model to
      predict treatmentfailure, defined as tubal rupture. RESULTS: Methotrexate
      treatment failed in 9 cases (15.5 %). Another 9 cases (15.5%) required a second
      dose of methotrexate, and no treatment failures were observed in these cases. The
      presence of subchorionic tubal hematoma in the ectopic gestation (OR = 22.9, CI =
      2.7-194.7, p = 0.004), the presence of an embryo (OR = 24, CI = 2.1-269, p =
      0.01) and day 1 serum beta-hCG level > or = 3,000 mIU/mL (OR = 27.1, CI = 2.1
      342.5, p = 0.01) were the main predictors of treatment failure. Follow-up serum
      beta-hCG levels > or =3,500 mIU/mL (OR = 42.9, CI = 4.3-421) on day 3 were
      significant predictors of treatment failure. Follow-up risk score was calculated
      as > 4 on day 3 by adding day 3 serum beta-hCG level to the admission score. Only
      1 treatment failure (2.4%) occurred in 42 patients with an admission score of
      nil. No treatment failure occurred in 39 patients whose follow-up score was nil.
      The increase in admission risk (OR = 32.1, CI = 3.8-270, p = 0.001) and follow-up
      risk (OR = 9.2, CI = 2.4-35.2) were significant predictors of treatment failure.
      CONCLUSION: Transvaginal ultrasound findings are as important as serum beta-hCG
      level on the first day of methotrexate treatment. In unruptured cases, day 3
      serum beta-hCG level is important to reevaluate the decision to continuefollow-up
      or perform early surgery for increased risk of treatment failure.

PMID- 16572909
TI  - Maternal asthma and risk of preeclampsia: a case-control study.
AB  - OBJECTIVE: To quantify the associations between asthma characteristics and the
      risk of preeclampsia. STUDY DESIGN: In this case-control study, asthma history
      among 286 preeclampsia cases and 470 normotensive controls in Seattle was
      assessed by postpartum interview and medical record abstraction. OR and 95% CI
      were estimated using logistic regression. The sample size was adequate to detect
      unadjusted asthma history with ORs of > or =1.6 at a power of 80%. RESULTS: After
      adjustment, women with a history of prepregnancy asthma diagnosis were not at
      increased preeclampsia risk (OR 0.94, 95% CI 0.58-1.52). Women experiencing
      asthma symptoms during pregnancy were more likely than pregnant nonasthmatics to
      have preeclampsia (OR 2.20, 95% CI 0.79-6.10). Those with long-term pre-pregnancy
      asthma and symptoms during pregnancy were at particularly increased risk (OR
      9.09, 95% CI 1.02-81.6). Point estimates were generally higher after restriction
      to women withfull-term deliveries. CONCLUSION: This analysis suggests that
      asthmatics, particularly those who are symptomatic during pregnancy, may be at
      higher risk of developing preeclampsia.

PMID- 16572910
TI  - Assessing perinatal hepatitis B screening and neonatal prophylaxis in a large,
      multiethnic county.
AB  - OBJECTIVE: To assess the completeness of maternal screening and appropriateness
      of newborn prophylaxis for hepatitis B virus (HBV) in 2001 in Florida's largest
      county. STUDY DESIGN: A retrospective cohort study sampled 1% of deliveries at
      all hospitals in Miami-Dade County that had delivery suites. Abstractors reviewed
      mothers' and newborns' charts before discharge to determine whether newborns
      received appropriate HBV prophylaxis based on mothers' hepatitis B virus surface
      antigen (HBsAg) status at 12 hours postpartum. At each hospital, deliveries were
      sampled sequentially until the target number was reached. Sampling was donefor
      March-August 2001. RESULTS: Among 339 deliveries at 14 hospitals, the mother's
      HBsAg status was known within 12 hours of delivery for 286, or 84.4% (95% CI 80.1
      88.1%). Of the 53 infants whose mothers' HBsAg status was unknown, 15 (28.3%)
      were vaccinated within 12 hours of delivery; both infants whose mothers were
      HBsAg positive received vaccine and immune globulin within 12 hours delivery.
      CONCLUSION: While HBsAg screening of pregnant women is widespread in Miami-Dade
      County, the information is not consistent used to protect infants who mothers'
      HBsAg status unknown.

PMID- 16572911
TI  - Patient acceptance of medical student participation in an outpatient
      obstetric/gynecologic clinic.
AB  - OBJECTIVE: To determine which patients, based on selected patient, physician and
      visit information, were more likely to accept medical student participation in an
      outpatient visit. STUDY DESIGN: A cross-sectional study conducted at a university
      based private practice, evaluated 560 patients presenting for routine outpatient
      obstetric or gynecologic care. Participants completed a consent form regarding
      medical student participation in their visit. Patient, visit and physician
      demographic variables were abstracted. Comparison groups were those patients who
      accepted vs. those who refused medical student involvement. RESULTS: The majority
      of patients (75.8%) accepted student participation in their care. Patients who
      were black, were new to the office, were scheduled to see junior faculty and were
      evaluated for a vaginal discharge were more likely to refuse student
      participation. Patients seen for urinary incontinence were more likely to agree
      to medical student participation. CONCLUSION: The majority of patients consented
      to medical student involvement. Using a brief survey, we identified patients who
      are more likely to allow medical students to participate in their visit. We will
      continue to query all patients regarding medical student teaching but will assign
      medical students accordingly to maximize their learning experience. We will also
      educate patients on the benefits of including medical students in the outpatient
      visit.

PMID- 16572912
TI  - Length of the second stage of labor as a predictor of perineal outcome after
      vaginal delivery.
AB  - OBJECTIVE: To evaluate possible risk factors for spontaneous and induced perineal
      damage during vaginal delivery. STUDY DESIGN: A prospective, observational study
      was conducted with 300 patients at 37-42 weeks of singleton gestation who
      presented in active labor. Sociodemographic data, birth circumstances and past
      medical history were obtained upon admission. Perineal damage was assessed before
      repair and 24 hours postpartum. A multiple logistic regression model was
      constructed to investigate independent risk factors for spontaneous perineal
      lacerations. RESULTS: Of 300 women included, 139 were primiparas. Episiotomy was
      performed in 32% of the population (62% in primiparas, 6% in multiparas).
      Spontaneous perineal tears requiring suturing occurred in 28%. Severe perineal
      tears (grades 3 and 4) occurred in 1%. Risk factors for adverse perineal outcome
      in the nonepisiotomy group included younger maternal age, non-Israeli ethnic
      background, use of epidural analgesia, nulliparity, shorter interval since last
      vaginal delivery, longer active phase and prolonged second stage. Prolonged
      second stage (> 40 minutes) and low parity were independent risk factors for
      perineal tears in a multivariable analysis. CONCLUSION: Identifying women in
      specific subgroups at high risk for perineal lacerations may minimize perineal
      damage. Women with a prolonged second stage of labor and low parity are prone for
      spontaneous damage and therefore deserve special attention.

PMID- 16572913
TI  - Molecular analysis of defects in the CFTR gene and AZF locus of the Y chromosome
      in male infertility.
AB  - OBJECTIVE: To investigate the frequency and potential impact of mutations and
      polymorphisms in the CFTR gene and deletions in AZF locus of the Y chromosome in
      patients with azoospermia (AZOO), cryptozoospermia (CRYPTO) or
      oligoasthenoteratozoospermia (OAT) who were to be included in an assisted
      reproductive technologies (ART) program. STUDY DESIGN: A total of 188 infertile
      men were enrolled in the study: 100 patients with AZOO, 38 with CRYPTO and 50
      with OAT. RESULTS: The CFTR gene mutations or IVS8-5T variant in at least 1
      allele was identified with similar frequencies among the AZOO (33%) and CRYPTO
      (21%) patients; 55% of the AZOO patients with normal spermatogenesis (NS) had
      mutations in 1 or 2 alleles. The novel R810G mutation in exon 13 was identified
      in 1 NS patient. The OAT or AZOO patients with Sertoli cell only syndrome (SCO)
      had mutations in the CFTR gene with similar frequencies to that in the general
      Polish population. The deletions in the AZF locus were detected in 20% of SCO
      patients, 11.5% of AZOO patients with maturation arrest and in 5% of CRYPTO
      patients. The other groups (NS, OAT) did not carry deletions in the region
      studied. CONCLUSION: Molecular diagnosis of the CFTR gene, Y chromosome deletion
      analysis and genetic counseling are necessary diagnostic elements for patients
      with male infertility, especially if the are included in an ART program.

PMID- 16572914
TI  - Gestational diabetes mellitus in Plymouth, U.K.: prevalence, seasonal variation
      and associated factors.
AB  - OBJECTIVE: To estimate the prevalence of and associated factors in gestational
      diabetes mellitus (GDM) and its seasonal variation. STUDY DESIGN: A clinic-based,
      prospective, case register study was conducted from January 1996 to December
      1997. A total of 4,942 consecutive Caucasian, pregnant women aged 15-46
      years,free of a history of diabetes mellitus, underwent random plasma glucose
      screening and a 75-g, 2-hour oral glucose tolerance test in Plymouth, U.K. The
      mean (SD) age of the women was 28.2 (5.5) years. Women with and without GDM were
      compared. RESULTS: The prevalence of GDM among the subjects was 1.8% (95% CI
      1.4,2.2). The prevalence of GDM increased with the mother's age and random plasma
      glucose level and decreased with the duration of pregnancy. Using a stepwise
      binary logistic regression model, older age (relative prevalence [RP] 1.08 [95%
      CI 1.04, 1.12]) and higher random plasma glucose (RP 2.99 [95% CI 2.51, 3.551)
      were significant predictors of GDM. The monthly prevalence of GDM ranged from
      2.9% (95% CI 1.5, 5.0) in June to 1.1% (95% CI 0.3,2.8) in November. The seasonal
      GDM rate ranged from 2.3% (95% CI 1.5, 3.2) in spring to 1.4% (95% CI 0.8, 2.3)
      in winter. The differences were not statistically significant for either the
      month (p = 0.82) or season (p = 0.41). CONCLUSION: The prevalence (1.8%) of GDM
      in this representative sample of Caucasian pregnant women was lower than the 3-5%
      typically reported in other European and North American studies, and there was no
      seasonal pattern.

PMID- 16572915
TI  - Inner myometrial laceration causing a massive postpartum hemorrhage: a case
      report.
AB  - BACKGROUND: Postpartum hemorrhage has many well-established etiologies. It may
      also be secondary to an inner myometrial laceration, a less frequent and more
      difficult entity to diagnose. CASE: A 31-year-old, white woman, gravida 4, para
      2012, at term underwent an uncomplicated spontaneous vaginal delivery. She gave
      birth to a 3,600-g female infant. An immediate massive postpartum hemorrhage
      ensued, unresponsive to medical therapy. No cervicovaginal lacerations or
      retained placental tissue was found. Uterine packing failed to control the
      bleeding. During laparotomy, exploration of the uterine cavity revealed a 4-cm,
      posterior and longitudinal inner myometrial laceration involving an actively
      bleeding large vessel. Repairing the laceration controlled the hemorrhage.
      CONCLUSION: Inner myometrial lacerations must be considered in the differential
      diagnosis of postpartum hemorrhage when all other commonly established causes
      have been excluded. During laparotomy and hysterotomy, evaluation and repair of
      an inner myometrial laceration controls the bleeding and avoids a hysterectomy.

PMID- 16572916
TI  - Sirenomelia in a monoamniotic twin: a case report.
AB  - BACKGROUND: Sirenomelia is a rare congenital malformation characterized by fusion
      of the lower extremities and is associated with renal agenesis and absent
      bladder. Oligohydramnios usually occurs early in pregnancy. CASE: A 21-year-old
      primigravida with a twin gestation was diagnosed with sirenomelia in 1 of the
      twins at 18 weeks; they were delivered at 34 weeks. The infant was in perfect
      respiratory condition, lived for 5 days and died of nonpulmonary causes.
      CONCLUSION: Absence of oligohydramnios in monoamniotic twins allows free movement
      of the fetus in utero, facilitates the visualization of fetal organs on
      ultrasound and aids early prenatal diagnosis. It also delays the death of the
      sirenomelia infant due to the improved respiratory condition.

PMID- 16572917
TI  - Eosinophilic perifolliculitis presenting as a painful cystic ovarian mass in a
      woman with fibromyalgia: a case report.
AB  - BACKGROUND: Autoimmune oophoritis is characterized by an ovarian lymphocytic
      infiltrate and is a rare finding in women with premature ovarian failure.
      Eosinophilic perifolliculitis is a possible variant of autoimmune oophoritis, of
      which the pathogenesis and natural history are largely unknown. CASE: A 45-year
      old woman, gravida 2, para 2, status post total abdominal hysterectomy, presented
      to her internist complaining of cyclic, throbbing, right lower quadrant pain. Her
      past medical history was significant forfibromyalgia. Pelvic ultrasound
      demonstrated a 2.3-cm, physiologic-appearing right ovarian cyst. Follow-up
      ultrasound showed a 2.2-cm, complex cyst on the right ovary that increased in
      size to 4.2 x 3.2 x 3.5 cm on repeat ultrasound 12 weeks later. Exploratory
      laparotomy and bilateral salpingo-oophorectomy were performed. Pathologic
      evaluation of the ovaries revealed a 3 x 2 cm regressing corpus luteal cyst with
      numerous eosinophils, lymphocytes, macrophages and plasma cells, infiltrating the
      cyst zoall. Serum antiovarian antibodies were positive. CONCLUSION: The patient's
      pathologic findings are consistent with the rare entity of eosinophilic
      perifolliculitis. The patient's history offibromyalgia is of particular interest
      given that both of these diseases may have an autoimmune etiology. Eosinophilic
      perifolliculitis should be considered in the differential diagnosis of
      premenopausal and perimenopausal women with pelvic pain and persistent cystic
      ovarian enlargement.

PMID- 16572918
TI  - Comparative study on the bioequivalence of two different gabapentin formulations.
      A randomised, two-period, two-sequence, crossover clinical trial in healthy
      volunteers.
AB  - The bioequivalence of two capsule formulations containing 400 mg gabapentin (CAS
      60142-96-3) was assessed in 24 healthy volunteers in an open, randomised,
      crossover, 2 periods x 2 sequences, with a minimum washout period of 7 days,
      single-dose study. Plasma samples were obtained at fixed time points, over 48 h
      (baseline (pre-dose), +0.5 h, +1 h, +1.5, +2, +2.5, +3, +3.5, +4, +8, +5, +6, +8,
      +10, +12, +24, +36 and +48 h after administration) and gabapentin concentrations
      were determined by means of an HPLC-MS method (LLOQ 50.2 ng/mL). Pharmacokinetic
      parameters used for bioequivalence assessment (AUCtlast, AUCinf and Cmax) were
      determined from the gabapentin concentration data using non-compartmental
      analysis. The results showed that all 90 % confidence intervals (obtained by
      ANOVA) were all within the predefined ranges: 93.87-111.87 % for Cmax 94.04
      108.21 % for AUCtlast and 94.23-108.29 % for AUCinf. Consequently, this
      bioequivalence study was well designed in order to conclude that the test
      formulation and reference formulation were bioequivalent in terms of rate and
      extent of absorption.

PMID- 16572919
TI  - Changes in butyrylcholinesterase activity and serum lipids after oxprenolol and
      glibenclamide treatments in non-diabetic rats.
AB  - The effects of chronic treatment with oxprenolol (CAS 6452-72-7, OXP, 15 mg/ kg/
      day) or glibenclamide (CAS 10238-21-8, GL, 2.5 mg/kg/day), or their combination
      administered for 6 and 12 weeks, on the butyrylcholinesterase (BuChE) activity in
      plasma and liver and on the plasma levels of triglycerides, total cholesterol and
      high density lipoprotein (HDL)-cholesterol were studied in normal, non-diabetic
      female rats. In all treated groups a significant increase of plasma BuChE
      activity was obtained after 6 weeks of either OXP (46 %), or GL (36 %) treatment,
      or of their concurrent application (24 %). After 12 weeks of treatment, the
      increase in enzyme activity was significant only in the OXP group. The BuChE
      activity in the liver was increased (between 3-25 %) in all treated groups except
      in one during 6 and 12 weeks of treatment. These effects of either OXP or GL, or
      their combination on BuChE activity in liver suggest their stimulating effects on
      enzyme synthesis. The changes of total plasma cholesterol in all groups were
      insignificant. On the other hand, HDL-cholesterol was significantly decreased in
      all treated groups. After 6 weeks of treatment, GL, OXP, or their combination
      caused a decrease in plasma HDL cholesterol by 19, 50 or 22 % respectively, when
      compared with the control group. After 12 weeks of GL, OXP, or GL+OXP
      administration, HDL-cholesterol plasma levels in treated groups were 32, 25 and
      22 % lower than in the control group. Treatment with GL, OXP, or GL+OXP during 6
      weeks had no significant effect on triglycerides level. However, after 12 weeks
      of GL, OXP, or GL+OXP administration, the triglycerides levels were significantly
      increased (9, 47 and 36 %) when compared with the control group. These results
      showed that the increase in BuChE activity might be the first sign of altered
      triglyceride and lipoprotein metabolism.

PMID- 16572920
TI  - Comparative study on the bioequivalence of two formulations of pravastatin. Data
      from a crossover, randomised, open-label bioequivalence study in healthy
      volunteers.
AB  - An open-label, randomised, crossover single-dose study, using two periods, two
      sequences, with a minimum washout period of 7 days, was conducted in order to
      assess the comparative bioavailability of a pravastatin (CAS 81131-70-6) 40 mg
      formulation and that of a reference formulation. Blood samples were collected up
      to +14 h post dosing, the plasma was separated and pravastatin concentrations
      were determined by high-performance liquid chromatographic method with tandem
      mass spectrometry detection (HPLC-MS/MS), with a lower limit of quantification of
      0.40 ng/mL. Bioequivalence analyses were conducted using two models. The main
      analysis was done according to a general linear model (model I) using
      formulation, period and sequence as fixed model effects, and subject(sequence)
      and residual as random effects; gender-related differences were investigated
      using ANOVA (model II), including formulation, period, sequence, gender, sequence
      by-gender interaction and gender-by-formulation interaction as fixed model
      effects and subject within sequence-by-gender interaction and residual as random
      effect. Mean values of the individual Cmax were 126.73 +/- 61.99 ng/mL and 123.52
      +/- 52.78 ng/mL for the test and reference, spectively. Mean +/- SD total area
      under the curve up to the last measurable concentration (AUClast) was 224.26 +/-
      104.74 ng x h/mL for the test formulation and 216.55 +/- 80.30 ng x h/mL for the
      reference formulation. Mean +/- SD total area under the curve (AUCinf) was 226.72
      +/- 104.69 ng x h/mL for the test formulation and 218.81 +/- 79.95 ng x h/mL for
      the reference. Terminal elimination half-life was 2.15 +/- 0.85 h for test and
      1.97 +/- 0.54 h for the reference. Ninety percent confidence intervals were
      comprised within the bioequivalence acceptance criteria (80-125 %) for all of the
      parameters analysed, both using model I and model II. Model II returned a
      statistically significant gender effect (p < 0.05) for Cmax, AUClast and AUCinf
      but the effect became non-significant (p > 0.05) when the dose was adjusted per
      body weight for all three parameters. The comparison between male and female mean
      body weight showed a significant difference: p = 0.03, 95 % confidence intervals
      68.27-76.93 kg (men), 56.84-60.61 kg (women). These results suggest that the
      effect of gender in the bioequivalence analysis in model I could be due to a
      difference in body weight between males and females. Both formulations were shown
      to be bioequivalent in terms of rate and extent of absorption, irrespectively of
      the model used.

PMID- 16572921
TI  - Mononuclear cell membranes: stabilization by reproterol and cromoglycate,
      destabilization by fenoterol and salbutamol.
AB  - Electron paramagnetic resonance (EPR) spectroscopy with spin labels 5- and 16
      doxyl-stearic acid (DSA) was used to differentiate between actions of beta
      agonists on human mononuclear cell membrane. Reproterol (CAS 13055-82-8),
      salbutamol (CAS 51022-70-9) and fenoterol (CAS 1944-12-3) compared to
      cromoglycate (CAS 15826-37-6) were used at concentrations of 10-100 nmol/l per
      10(7) cells. With reproterol, order and polarity was not much changed, whereas
      salbutamol and fenoterol significantly destabilized the membrane to similar
      extent. Cromoglycate acted in a stabilizing fashion. With trypan blue exclusion,
      reproterol and cromoglycate showed stable values, whereas salbutamol and
      fenoterol augmented permeability. Thus, by conventional lipid spin labeling the
      discrimination between salbutamol and fenoterol could not be carried out. In
      contrast, previous lipid peroxidation studies in a model system had revealed a
      decrease by reproterol, no change by salbutamol and an increase by fenoterol.
      Also, using fenoterol, protein spin label 4-maleimido-TEMPO (2, 2, 6, 6
      tetramethyl-1-piperidinyloxy) showed an increase of membrane rigidity of
      mononuclear cells. Moreover, mast cells of different origin were previously found
      tween beta-agonists. Reproterol in all tests behaved in a therapeutically
      profitable way. In conclusion, in addition to lipid spin labeling other methods
      and materials should be considered, to finally arrive at a more realistic
      differentiation between, for instance, salbutamol and fenoterol. The term
      "membrane (de) stabilization" should not generally be used without careful
      consideration of the type of cell/membrane in question.

PMID- 16572922
TI  - In vitro disintegration and dissolution and in vivo bioequivalence of two
      alendronate once-weekly formulations.
AB  - Bioequivalence of two tablet formulations of 70 mg alendronate (CAS 121268-17-5)
      was assessed in a single-dose, open-label, randomised, fasted state crossover
      trial, with a washout period of 21 days, in 80 healthy subjects. Urine samples
      were collected up to +36 h post dosing and the concentrations of alendronic acid
      were assessed using a high-performance liquid chromatographic method with pre
      derivatization and fluorescence detection (HPLC/FL) method. The 90 % confidence
      intervals (90 % CI) obtained for Ae0-36 (cumulative urinary excretion) and Rmax
      (maximum rate of urinary excretion) were 98.67-118.99 % and 102.22-122.46 %,
      respectively. The intra-subject coefficient of variation was between 32-35 % for
      both parameters. No relevant tolerability problems were detected. Both
      formulations can be considered bioequivalent. In vitro testing was performed to
      confirm the adequacy of the quality control conditions and no significant
      differences were detected neither in the disintegration test nor in the
      dissolution tests conducted in HCl 0.1 N and H2O and thus in these conditions the
      lack of statistically significant differences in vitro was accompanied by in vivo
      bioequivalence.

PMID- 16572923
TI  - Beneficial effects of melatonin on diaphragmatic contractility and fatigability
      in Escherichia coli endotoxemic rats.
AB  - Sepsis impairs diaphragmatic contractility and endurance capacity and increases
      diaphragmatic fatigability. Several investigations have shown that administration
      of a number of free radical scavengers, such as N-acetylcysteine (NAC), protects
      the diaphragm from the development of endotoxin-mediated diaphragmatic
      dysfunction. The aim of this study was to evaluate the effects of melatonin (CAS
      73-31-4), a naturally occurring potent antioxidant, on diaphragmatic
      contractility and lipid peroxidation as a marker of oxidative stress in
      endotoxemic rats. Rats were randomly divided into four groups: control group,
      endotoxemic group, melatonin group and endotoxemic plus melatonin group.
      Melatonin was administered by intraperitoneal injection 30 min before endotoxin
      inoculation to animals. Diaphragmatic function and malondialdehyde (MDA) level
      analysis as an indicator of lipid peroxidation were assessed 17 h after endotoxin
      or saline inoculation. Endotoxemia decreased the development of diaphragm fatigue
      and diaphragmatic MDA levels. The effects of endotoxemia on diaphragmatic
      contractions and fatigability were reversed and returned to control levels by
      melatonin administration. However, melatonin did not prevent the increase in
      muscle MDA content. In conclusion, the present study demonstrated that melatonin
      attenuated the endotoxin-induced impairment of diaphragm function. This effect of
      melatonin does not seem to be related to its antioxidant properties.

PMID- 16572924
TI  - Synthesis and preliminary screening of carbohydrazides and hydrazones of pyrrole
      derivatives as potential tuberculostatics.
AB  - Five carbohydrazides and 19 hydrazones of carboxylic acids of pyrrole were
      synthesized as new structural analogs of known tuberculostatics, such as
      isoniazid (CAS 54-85-3) and its popular hydrazones. The preliminary screening
      against Mycobacterium tuberculosis H37Rv (ATCC 27294) at 6.25 microg/mL in 12B
      medium using a broth microdilution assay, the Microplate Alamar Blue Assay (MABA)
      registered higher inhibitory activity within the hydrazones series (up to 68 %
      inhibition) compared with that of the carbohydrazides (0-34 %). No simple
      relationship between the activity of a particular hydrazone and that of the
      parent carbohydrazide, or correlations with the structural features introduced by
      the carbonyl partner could be observed. So both most active hydrazones diethyl 5
      (2-[(2,4-dimethyl-1H-3-pyrrolyl)carbonyl]hydrazonomethyl)-3-methyl-1H-2,4
      pyrroledicarboxylate (22, 68 % inhibition) and ethyl 5-(4-chlorophenyl)-2-methyl
      1-(2-2-1-(5-nitro-2-furyl)methylidene]hydrazino-2-oxoethyl)-1H-3
      pyrrolecarboxylate (32, 55 %) originated from inactive carbohydrazides (1, 0 %
      and 7, 10 % respectively); ethyl 1-(2-2-[1-(3-ethoxy-4-hydroxyphenyl)
      methylidene] hydrazino-2-oxoethyl)-2-methyl-5-(4-nitrophenyl)-1H-3
      pyrrolecarboxylate (30) showed 0 % inhibition, although derived from a hydrazide
      with 34 % activity. The condensation of six carbohydrazides with the same
      carbonyl reagent 5-nitrofurfural yielded hydrazones whose activity covered the
      wide range of 0-55 % inhibition.

PMID- 16572925
TI  - Assessment of the toxicity of Artemisia inculta extract on the bone marrow of
      mice infected with schistosomiasis.
AB  - The discovery of the crude extract of Artemisia inculta (an Egyptian species of
      the Artemisia plant) for the therapy of schistosomiasis has evoked the study of
      its long-term toxicity produced by antischistosomal doses. Hence, an assessment
      of the noxious effects on bone marrow was attempted in this study. Transmission
      electron microscopy of the bone marrow was conducted on infected mice receiving a
      crude ethanolic extract from Artemisia inculta by newly designed dose regimens
      (500 or 800 mg/kg body weight in the 7th, 14th and 21st weeks post infection).
      This regimen was found to produce an efficient therapeutic effect in decreasing
      worm load and causing tegumental damage of juvenile and adult worms. The
      ultrastructural features of all cell lines in the bone marrow were comparable in
      both treated (500 and 800 mg/kg body weight dose levels) and untreated groups
      showing normal cellularity, maturation and morphology. This denotes that the drug
      is non-toxic to the hemopoietic tissue. IN CONCLUSION: Electron microscopy has
      provided a direct and accurate evidence of the nontoxic property of the plant
      extract on bone marrow using therapeutic doses. However, this study should be
      extended to other vital organs such as the liver or brain to establish the safety
      of this drug.

PMID- 16572926
TI  - Pharmacological concept for topical synergistic analgesia of peripheral
      neuromuscular pain.
AB  - A pharmacological concept of topical peripheral pain therapy with a combination
      of a sodium channel blocker from the class of local anesthetics and a non
      steroidal anti-inflammatory drug (NSAID) from the class of nonselective/
      partially selective cyclooxygenase (COX) inhibitors is described. The dual
      mechanism of action of these substances on the cellular level interferes with
      pain components of both inflammatory and neuronal genesis and is functionally
      synergistic. This enables the combination of these agents to produce a more long
      lasting analgesia than is attainable with either of the substances alone. The
      therapeutic indication is the symptomatic reduction of neuromuscular pain of
      traumatic or metabolic origin. The already more favorable safety profile for
      topical applications can be improved further by a possible dose reduction of the
      two substances.

PMID- 16572927
TI  - Nicotine an efficient tool of the neurobiological research today, the tool of
      treatment tomorrow?
AB  - Nicotine is a very widely used drug of abuse, which has many neurovegetative
      behavioural and psychological effects by interacting with neuronal nicotinic
      acetylcholine receptor. Cholinergic receptors can be divided into two types,
      muscarinic and nicotinic, based on the pharmacological action of various agonists
      and antagonists. This review summarises the major recent findings of nicotine
      effects in order to show the use of this drug in the neurophysiological research
      and namely as a potential tool for the treatment of some brain disorders.

PMID- 16572928
TI  - Mutans streptococci and the development of dental plaque.
AB  - A study of dental plaque was first documented in the literature of the 17th
      century. It has been described as a biofilm composed of bacterial populations
      living in a plaque matrix. The plaque development starts short time after a tooth
      surface is cleaned and covered by salivary proteins and glycoproteins
      conditioning film. Mutans streptococci was described as the most important
      bacteria related to the etiology of dental caries. This bacteria has the basic
      properties of cariogenicity required in the dental caries process. Current
      studies have suggested that the behaviour of the oral microflora, with all its
      components, should be the aim of future understanding of the process of dental
      caries. The aim of this paper is to review literature about initiation and
      development of dental plaque and the influence of mutans streptococci in the
      dental caries.

PMID- 16572929
TI  - Mast cells, hypoxia and structure of the vascular bed.
AB  - Mast cells represent a heterogeneous and multifunctional cells population
      distributed throughout tissues. Their participation in the response to chronic
      hypoxia is discussed in consideration to their role in the angiogenesis and
      remodeling of pulmonary vasculature, including relevance of proangiogenic
      factors, mediators and proteolytic enzymes released by activated mast cells.
      Possible mechanism of mast cells activation by hypoxia is considered.

PMID- 16572930
TI  - Third molar as an age indicator in young individuals.
AB  - The authors developed a method of chronological age estimation in young
      individuals on the basis of third molar developmental stage. The new method is
      based on the finding that time course of third molar development depends on the
      number of assessed third molars. That means, in individuals with 1 to 3 third
      molars agenesis the development of founded third molars is delayed in comparison
      with individuals having all third molars present. This difference is
      statistically significant. Retardation of development is directly proportional to
      the number of congenitally missing third molars. Chronological age corresponding
      to individual stages of third molar development was calculated separately for
      individuals with all four third molars present and separately for individuals
      with 1 to 3 third molars agenesis. With this division it was possible to decrease
      the error of age estimation to 1.63 years in the group of individuals with all
      four third molars present and to correct the age underestimation in individuals
      with agenesis. The elaborated method of chronological age estimation in young
      individuals shows incomparably much more accuracy in contrary to methods used in
      adults. In addition this new method is distinguishing by maximum simplicity.

PMID- 16572931
TI  - Serum levels of antibodies to thyroid peroxidase correlate with quantitative
      descriptors of thyroid ultrasound images in patients with breast cancer.
AB  - The aim of the study was to compare the structural changes in ultrasound image of
      the thyroid tissue in 12 women with breast cancer (BC) and 8 women with
      colorectal cancer (CC). MATLAB software was used to analyse the digitised images.
      As quantitative descriptors of thyroid ultrasound images (QDTI) were used raw
      grey scale values of individual image pixels (RAW) and the optimal one
      dimensional discriminative texture features (F2, F6, F7). The possible relations
      between QDTI and thyroid laboratory parameters were tested. In the BC group serum
      levels of antibodies to thyroid peroxidase negatively correlated with feature RAW
      (multiple regression, beta coefficient -0.75, p=0.004) and positively with
      feature F2 (multiple regression, beta coefficient 1.44, p=0.04). In the BC group
      RAW negatively correlated with serum levels of tumour marker CA 15-3 (Pearson's
      correlation coefficient, r=-0.714, p=0.00917). No such correlations were found in
      CC group. The correlations between QDTI and serum levels of antibodies to thyroid
      peroxidase in patients with BC show that the positivity of antibodies to thyroid
      peroxidase is probably accompanied with structural changes in the thyroid tissue.

PMID- 16572932
TI  - Time precision of hippocampal CA3 neurons.
AB  - Time precision of generation of action potentials (AP) is limited by the
      electrical properties of neuronal membrane, by the probabilistic nature of
      synaptic transmission and by the membrane noise. In the software environment
      GENESIS 2.2, we constructed a multicompartmental model of a rat hippocampal
      neuron, made up of soma, dendritic tree and axonal initial segment (IS). In the
      model were implemented channel and thermal noise, corrupting the propagation of
      postsynaptic signal at the soma-dendritic (SD) membrane and the AP initiation at
      the IS. Various levels of synaptic redundancy, connecting the presynaptic neurons
      with the SD membrane by various numbers N of unreliable synapses of varying
      probability P of vesicle release, were modelled. During simulations, random
      spatio-temporal patterns of synaptic activity were presented to the neuron
      repeatedly, eliciting sequences of APs, which were further statistically
      processed. The influence of P, N, channel and thermal noise on the time precision
      of AP generation was tested by repeated stimulation of identical input. The
      precision was mostly influenced by the synaptic unreliability and substantially
      dependent upon values N and P. The channel noise was about an order less
      corruptive than the synaptic unreliability, causing the time precision of
      neuronal responses to vary from submilliseconds to tens of microseconds,
      depending on the values P and N.

PMID- 16572933
TI  - Gonococcal infection as a cause of acute abdomen.
AB  - Gonococcal infection in the postantibiotic era continues to cause disseminated
      and severe disease in some patients. The differential diagnosis of pain in the
      lower abdomen in young women is difficult. Our case report described a 19-year
      old patient who presented with acute abdomen as a result of Gonococcal infection,
      assessed as a local complication, pelveoperitonitis: pelvic inflammatory disease.
      The message of our case report is sexually transmitted infections should
      invariably be considered in young women and searched for accordingly.

PMID- 16572934
TI  - Good issue, one question.

PMID- 16572938
TI  - Technology. CPOE: are you really ready?

PMID- 16572939
TI  - Staffing. Filling a void on and off the job.

PMID- 16572940
TI  - Payment. Drunk denials.

PMID- 16572941
TI  - Improving diagnostics. Family portraits.

PMID- 16572942
TI  - Workforce. Dangerous jobs.

PMID- 16572943
TI  - Katrina aftermath. 'Don't forget us'.

PMID- 16572944
TI  - The data page. Americans unaware of health care disparities.

PMID- 16572945
TI  - Taking inventory.
AB  - The eighth annual Most Wired Survey and Benchmarking Study is ready for the
      taking. It's an opportunity to get a comprehensive view of your hospitals IT
      systems and see how you stack up against your peers.

PMID- 16572946
TI  - Built to crash.
AB  - The first article in our IT cover package looks at how hospitals often invest
      huge sums of money on the latest clinical technology, but fail to build the
      infrastructure to support it. In the second article,"Digital Docs," Senior Editor
      Matthew Weinstock examines the growing trend among hospitals to hire physicians
      to lead their clinical IT efforts.

PMID- 16572947
TI  - Built to crash. Digital docs.

PMID- 16572948
TI  - A primer for building RHIOs.
AB  - We outline the basics of creating regional health information organizations to
      foster the digital exchange of data. What are the goals, pitfalls and lessons
      learned by pioneers?

PMID- 16572949
TI  - Tracking infections.
AB  - Hospitals expect that new computerized techniques to pinpoint and track
      nosocomial infections will reduce deaths and slash billions of dollars in excess
      costs.

PMID- 16572950
TI  - Covering your staff: high costs, tough choices.
AB  - Like all employers, hospitals are squeezed by the skyrocketing cost of employee
      health coverage. Some are taking a relatively radical step: offering consumer
      directed plans.

PMID- 16572951
TI  - A tale of two turn arounds.
AB  - Several years ago, two financially strapped hospitals were teetering toward
      closure. Vigorous and inspired leadership brought them back from the brink.

PMID- 16572952
TI  - Quick change. The change acceleration process has been used successfully in
      business all over the world.

PMID- 16572953
TI  - Motivation for better nursing management.

PMID- 16572954
TI  - Mania (BPAD)--case study.

PMID- 16572955
TI  - The burden of haemoglobinopathies in India--time to wake up?

PMID- 16572956
TI  - Spectrum of hemoglobinopathies in the state of Orissa, India: a ten years cohort
      study.
AB  - OBJECTIVES: i) To determine the pattern of spectrum of hemoglobinopathies in the
      state of Orissa, ii) To find the ethnic groups at high risk of
      hemoglobinopathies, iii) Geographical distribution of hemoglobinopathies, and
      iv). To know epidemiological aspects of hemoglobinopathy cases in Orissa.
      MATERIAL AND METHODS: One thousand fifteen cases of anemia were analysed referred
      from different peripheral hospitals and Medical Colleges and Hospitals of Orissa
      state for diagnosis and counseling during 1994 to 2003. About 2-3 ml. intravenous
      blood samples were collected after obtaining informed consent from each
      individual. Hematological indices were measured using MS4 Cell Counter.
      Background data of each individual were recorded like age, sex, caste, place of
      origin, consanguinity, etc. Hemoglobin electrophoresis was carried out on CAM in
      Tris-EDTA-Borate buffer at pH 8.9 and quantification of A2 fraction of hemoglobin
      by elution method. The value more than 3.5% of A2 fraction of hemoglobin was
      taken as cut off point for beta-thalassemia trait and more than 10% as Hb E. Hb
      electrophoresis in acidic medium (pH 6.2) was also carried out to confirm Hb D or
      E band. Estimation of fetal hemoglobin was done. Family studies were carried out
      to confirm the diagnosis. RESULTS: Most common hemoglobinopathies observed out of
      1015 cases were: sickle cell trait (29.8%), sickle cell disease (7.5%), sickle
      cell-beta-thalassemia (1.7%), beta-thalassemia trait (18.2%), thalassemia major
      (5.3%), thalassemia intermedia (0.9%), Hb E trait (0.9%), Hb E disease (0.3%), E
      beta-thalassemia (0.7%), Hb D trait (0.2%) and SD disease (0.2%). Sickle cell
      disorders with high level of fetal hemoglobin were common in general castes (0.3
      20.7%), scheduled castes (0-8.9%) and scheduled tribals (0-5.5%). Transfusion
      dependent beta-thalassemia syndrome was prevalent in Brahmin, Karan, Khandyat,
      Teli, etc. Most of the cases belong to Anugul district, followed by Khurda,
      Nayagarh, Phulbani, Cuttack, Jajpur, Dhenkanal, Ganjam, Keonjhar, Mayurbhanj,
      etc. CONCLUSIONS: The heterogeneous population is harbouring almost all major
      hemoglobinopathies in general castes, scheduled castes and tribes, belonging to
      Coastal and South-Western regions of Orissa. This study provides for the first
      time a comprehensive database on the pattern of spectrum of hemoglobinopathies in
      Orissa.

PMID- 16572957
TI  - Hematological findings and severity of G6PD deficiency in Vataliya Prajapati
      subjects.
AB  - OBJECTIVES: The present study was undertaken to assess the clinical implication
      of G6PD deficiency in Vataliya Prajapati (VP) subjects in Surat. METHOD: Blood
      samples of 954 children and 690 adults were collected in camps. Cord blood
      samples of 57 neonates born to VP mother were also collected. Medical history and
      other relevant information of all subjects were obtained. Samples were screened
      for G6PD deficiency by NBT test and the enzyme activity was estimated by WHO
      method. Hematological parameters were measured on hematology analyzer while
      reticulocyte count was measured using new methylene blue dye. RESULTS: The G6PD
      enzyme deficiency was detected in 27.5% males and 12.8% females. The enzyme
      levels in deficient subjects suggested class II variant. Hematological studies
      indicated mild anemia in G6PD deficient persons. Reticulocyte count was slightly
      raised (p <0.05). Out of eight G6PD deficient neonates one developed mild
      jaundice. Five deficient male adults gave the history of hemolytic crisis, three
      of them had typhoid, one tuberculosis and remaining one had fever of unknown
      origin. CONCLUSION: G6PD deficiency in majority of Vataliya Prajapati subjects is
      of mild type. However it is essential to test every Vataliya Prajapati subject
      for G6PD deficiency as certain infections and drugs can cause crisis in deficient
      person.

PMID- 16572958
TI  - Correlation of CD34+ cell yield in peripheral blood progenitor cell product with
      the pre-leukapheresis cell counts in peripheral blood.
AB  - INTRODUCTION: Accurate timing of the leukapheresis procedures is of paramount
      importance to get the best possible CD34+ cell yield in the minimum number of
      leukapheresis procedures. AIM: To find if pre-harvest CD34+ cell concentration in
      peripheral blood correlates with CD34+ cells in the product. MATERIAL AND
      METHODS: Sixty Leukapheresis procedures were performed for 25 patients (8
      autologous and 17 allogeneic transplants) with hematological malignancies.
      Statistical analysis was performed to correlate the pre-harvest CD34+ cell count
      and the CD34+ cell yield. Volume processed during PBPC harvests was three times
      the blood volume. RESULTS: The best correlation was found between the
      leukapheresis product CD34+ cell count and the pre-harvest PB-CD34+ cell count
      (PCC=0.674) when compared with the other pre-harvest PB cell counts viz., WBC
      (PCC=0.229) and MNC (PCC=0.324). This correlation was better in the allogeneic
      harvest (PCC = 0.645) than the autologous harvest procedures (PCC = 0.348).
      Correlation analysis based on paired samples from the 60 leukapheresis procedures
      showed that when the pre-leukapheresis PB-CD34+ cell count was >20x10(3)/ul a
      yield of >1x10(6) CD34+ cells/Kg could be obtained in 95% of the cases and
      >2x10(6) CD34+ cells /Kg could be harvested in 68% of cases whereas when the pre
      leukapheresis PB-CD34+ cell count was <5x10(3)/microl the yield was <1x10(6)
      CD34+ cells/Kg in 81% of the procedures. CONCLUSION: The yield of CD34+ cells in
      PBPC harvests depends on the pre-harvest CD34+ cell concentration and therefore
      it is more useful than the pre-harvest WBC or MNC counts for predicting the
      appropriate timing of the harvests and also to achieve the best possible yield of
      CD34+ cells.

PMID- 16572959
TI  - Prognostic value of 99mTc-Sestamibi stress Myocardial Perfusion Single Photon
      Emission Computed Tomography (SPECT) in ischemic heart disease.
AB  - AIM: To study prognostic value of 99mTc-Sestamibi stress Myocardial Perfusion
      Single Photon Emission Computed Tomography (SPECT) in suspected or diagnosed
      ischemic heart disease, in an urban Indian population. METHODS: Eight hundred and
      eighty one patients with clinically suspected or diagnosed ischemic heart disease
      who underwent 99mTc-MIBI stress-rest Myocardial Perfusion SPECT (MPS) between 1st
      February 2001 to October 2002 were followed up for 14 +/- 2 months after the scan
      by questionnaire and telephonic interview with queries about cardiac death,
      myocardial infarct (hard events) and admission for unstable angina, CABG and PTCA
      (soft events). Patients were classified into pre-test: low, intermediate or high
      risk subsets based on clinical risk factors and ECG criteria. They were then
      reclassified based on MPS scan into post-test: high, intermediate and low risk
      subsets. Subsequent cardiac event rate was compared in the three subsets. A 12
      lead ECG was an integral component of the stress MPS evaluation. RESULTS: MPS
      changed (1) the pre-test low risk category in 114 out of 613 patients to
      intermediate and 102 to high risk; (2) pre-test intermediate risk in 110 patients
      out of 163 to low risk and 19 patients to high risk (3) pre-test high risk
      category in 56 patients out of 105 to low risk and 28 to intermediate risk (total
      change 429 out of 881 patients). The hard cardiac event rate at one year was less
      than 0.5% in low risk, 2.3% in intermediate risk and 4.2% in high risk group.
      CONCLUSIONS: 99mTc-Sestamibi stress SPECT MPS thus provided incremental
      information for prognostic evaluation of patients with suspected or diagnosed
      coronary artery disease by assessing the effect of ischemic burden on LV
      function. This incremental information is crucial since coronary arteriography
      alone is not enough for prognosis and management decisions. Patients with a
      normal or low risk MPS have generally a benign prognosis with a low annual hard
      cardiac event rate of 0.5%. Future challenge is to identify high risk subsets
      within this group, with CT coronary calcium score > or = 100 and inflammation
      markers such as high hsCRP so that more aggressive secondary preventive measures
      can be instituted to prevent future hard cardiac events.

PMID- 16572960
TI  - Postprandial lipid abnormalities in type 2 diabetes mellitus.
AB  - AIM AND OBJECTIVES: To study the postprandial lipid abnormalities in patients
      with type 2 diabetes mellitus. MATERIAL AND METHODS: Postprandial lipids were
      studied in 20 male type 2 diabetic subjects (age 49.75 +/- 4.82 years) and 20 age
      and sex matched healthy controls (age 49.55 +/- 4.82 years) after an oral fat
      challenge which consisted of a meal providing 729 keal/m2 body surface area with
      68 gm fat. RESULTS: Average duration of diabetes among diabetic was 2.32 +/- 3.03
      years. The body mass index (cases 25.84 +/- 4.52; controls 25.74 +/- 5.0; p >
      0.05) and waist-hip ratio (cases 1.06 +/- 0.13; controls 1.14 +/- 0.2; p > 0.05)
      were similar in both groups. While fasting serum lipids were not significantly
      different between the two groups, a number of serum lipid abnormalities were
      noted in type 2 diabetic subjects in the postprandial state. These included a
      higher triglyceride-area under curve (AUC) (cases 1298.08 +/- 485.2 vs. controls
      922.15 +/- 390.47 mg/dl/8h; p=0.01), a higher triglyceride-area under incremental
      curve (AUIC) (cases 549.68 +/- 382.24; control 294.75 +/- 172.6 mg/dl/8h;
      p=0.01), a higher peak triglyceride level (cases 425.2 +/- 204.47 mg%, controls
      283.9 +/- 11.6.94 mg%, p=0.01), a lower HDL-AUC (cases 130.35 +/- 33.55 vs.
      controls 168.48 +/- 56.01 mg/dl/8h, p=0.013) and a lower HDL nadir (Cases 28.05
      +/- 10.94 mg%, controls 37.13 +/- 13.52 mg%, p < 0.02). Triglyceride AUC
      correlated significantly with fasting serum triglyceride (r=0.62) and BMI
      (r=0.7), but not with waist hip ratio or fasting serum insulin levels.
      Postprandial lipaemia did not correlate with age, duration of diabetes, fasting
      blood glucose or glycosylated hemoglobin. CONCLUSION: In conclusion, make type 2
      diabetics demonstrate significant postprandial lipid abnormalities, particularly
      of triglycerides, which appear to be independent of glycaemic control.

PMID- 16572961
TI  - Lady with melanuria and arthralgias.

PMID- 16572962
TI  - Nocardiosis in AIDS--an unusual presentation.

PMID- 16572963
TI  - Electricity and the heart.
AB  - Understanding of cardiac rhythm requires application of physical principles
      governing electricity. Over a period of more than 100 years, application of the
      knowledge of electric current led to the gradual evolution of electrocardiogram,
      pacemaker, defibrillator, and ultimately electrophysiology. The discovery of
      electrocardiogram (ECG) by Einthoven in 1902 and that of pacing by Zoll in 1952
      were two landmarks in this field.

PMID- 16572964
TI  - Multiple myeloma: treatment options for an incurable disease.
AB  - Multiple myeloma remains a challenge for the treating physician, with extremely
      low complete response rates (5-10%) to conventional induction therapy. High dose
      therapy with autologous hematopoietic stem cell transplant results in improved
      response, event-free and overall survival and should be considered the standard
      of care for patients who are candidates for transplantation. Several newer
      treatment option are now available.

PMID- 16572965
TI  - Sir Ram Nath Chopra (1882-1973). Postal stamps released on Sir Ram Nath Chopra,
      India and Sarpagandha, India--1997.

PMID- 16572966
TI  - Recurrent lymphocytic hypophysitis in a woman 27 years after subtotal
      adrenalectomy for hypercortisolism possibly of autoimmune origin.
AB  - Lymphocytic hypophysitis commonly occurs in females in peripartum period but
      several unusual presentations have been reported. Here we report a rare case of
      recurrent lymphocytic hypophysitis in a woman who had subtotal adrenalectomy for
      hypercortisolism 27 years back. Polyglandular autoimmune endocrinopathy with an
      uncommon combination of Cushing's syndrome and recurrent hypophysitis is a strong
      possibility in this case. Treatment with steroids has been found to have
      beneficial effect.

PMID- 16572967
TI  - Pulmonary hydatid cyst in HIV-1 disease.
AB  - A 36-year-old male patient, a known case of retroviral disease, presented with
      clinical features suggestive of pneumonia and was found to have bilateral lower
      zone lung consolidation which on resolution showed a cystic change on the chest
      radiograph. A subsequent CT scan revealed the true nature of these cysts to be
      ruptured pulmonary hydatid cysts showing a 'water lily sign'. The rare
      association of pulmonary hydatid cyst and HIV from India is described.

PMID- 16572968
TI  - Systemic lupus erythematosus presenting with recurrent pleural effusion without
      any systemic manifestation.
AB  - Pleural effusion can be the sole presenting manifestation in about 5 percent of
      cases with SLE. We are reporting a case of SLE which presented with recurrent
      pelural effusion without other systemic manifestation.

PMID- 16572969
TI  - Relationship of prevalence of gestational diabetes mellitus with maternal
      hemoglobin.

PMID- 16572970
TI  - Primary pneumaturia.

PMID- 16572971
TI  - EBV-associated hepatitis with aplastic anemia.

PMID- 16572972
TI  - Profile of clinical presentations of HIV infected patients in rural West Bengal.

PMID- 16572973
TI  - Workshop on "role of nurses in disaster preparedness and management".

PMID- 16572974
TI  - Stable transport: safe neonate.

PMID- 16572975
TI  - Nurses' knowledge about genetics.

PMID- 16572976
TI  - Accredited Social Health Activist (ASHA)--the trained woman community health
      volunteer.

PMID- 16572977
TI  - Hypothermia in newborn babies.

PMID- 16572979
TI  - National Rural Health Mission.

PMID- 16572980
TI  - A study on knowledge of married men on no-scalpel vasectomy.

PMID- 16572981
TI  - Liver abscess--a case study.

PMID- 16572982
TI  - [Management of acute chest pain in the emergency department].
AB  - Acute chest pain is one of the most common symptoms in emergency departments.
      Immediate assessment is mandatory on arrival in order to ensure the appropriate
      care. Diagnostic work-up should be based on conventional tools, i.e. clinical
      presentation, physical examination, electrocardiogram, as well as on modern
      information, i.e. biochemical markers of myocardial damage or provocative tests.
      Firstly, physicians should assess the likelihood that signs and symptoms have a
      cardiac origin secondary to coronary artery disease. Afterwards, the risk for
      ischemic complications should be stratified. To this end, several scores have
      been derived from clinical trials in order to improve prediction of outcome.
      Also, use of critical pathways can improve guideline adherence. In the "real
      world", a variety of barriers to optimal management of acute chest pain still
      exists. An agreement on specific protocols is often difficult to achieve between
      different specialties. Also, no official guidelines on low-risk chest pain
      patients or patients with non-cardiac chest pain are available. Finally, the
      minimal data set of diagnostic tools that should be applied in case of acute
      chest pain in any emergency setting is still lacking.

PMID- 16572983
TI  - [Secondary prevention of acute coronary syndromes: are we following correctly the
      guidelines?].
AB  - Heart diseases are the leading cause of death and morbidity in western countries
      and among them acute coronary artery diseases result to be the major contributor.
      During the last few decades a lot of energy has been mostly applied to the acute
      phase of non-ST-elevation acute coronary syndromes (ACS), where cardiac events
      concentrate. In fact a timely risk stratification along with an early aggressive
      invasive strategy and very powerful antithrombotic treatment have profoundly
      improved the in-hospital prognosis of such patients. Such a strong emphasis on
      the acute phase of ACS could have limited the interest in the equally important
      post-discharge therapies. However, several studies have demonstrated that
      different preventive treatments (aspirin, beta-blockers, angiotensin-converting
      enzyme inhibitors, statins and clopidogrel) could substantially reduce the long
      term mortality and morbidity of such patients. Therefore, current guidelines
      emphasize the role of aggressive secondary preventive treatments after ACS.
      However, a strong discrepancy between the indications of the guidelines and their
      application in the real world arises day by day. Such a discrepancy could be due
      to errors of omission or therapeutic paradoxes. Since patients with ACS are a
      subgroup of subjects where secondary preventive measures could be useful and cost
      effective, cardiologists should not limit their attention to the acute phase of
      the disease but should eagerly concentrate their efforts on an aggressive
      secondary preventive treatment as well. Pursuing such a task could extend and
      magnify the benefits obtained with acute treatment of ACS and significantly
      improve the outcomes of such patients. Therefore, the role of the Scientific
      Societies is to improve the application of guidelines and the utilization of all
      evidence-based treatments even in such post-discharge phase.

PMID- 16572984
TI  - [Chronic heart failure as a crisis event of the family].
AB  - The family greatly influences any of its members and significantly contributes to
      the patient rehabilitation. A limited and superficial interest from the family as
      well as an overprotective and anxiogenic behavior may lead to chronicization,
      relapse or even to progression of the disease. The close relationship between the
      patient and the physician is an illusion, since family members deeply affect this
      interaction. They may first influence the cardiologist's choice and later,
      through comments or actions, treatment expectations, diagnosis and therapy by
      sustaining or, on the contrary, minimizing the patient-physician interaction. A
      therapeutic triangle, which includes the family, the patient and the physician,
      develops from the beginning; thus the physician needs to be aware of it to use
      these interactions in the best interest of the patient himself. In this context
      clinical psychologists play a pivotal role first in identifying dysfunctional
      relations within the family and then in supporting the family to overcome crisis
      events.

PMID- 16572985
TI  - [Non-pharmacological treatment of hypertrophic obstructive cardiomyopathy guided
      by echocardiography].
AB  - As a relevant cause of symptoms and adverse clinical prognosis, left ventricular
      obstruction should be regarded as an important therapeutic target in patients
      with hypertrophic obstructive cardiomyopathy. The surgical approach (including
      septal myectomy or mitral valve surgery) and percutaneous transluminal septal
      myocardial ablation offer a non-pharmacological option for the treatment of
      symptomatic left ventricular obstruction and symptoms unresponsive to medical
      treatment. The surgical approach is established as an effective strategy for
      relieving symptoms from dynamic obstruction. Percutaneous septal ablation, on the
      other hand, has only recently been introduced into clinical practice and, despite
      its efficacy as an obstructive abolisher, little is known about the prognostic
      long-term impact of procedural-induced myocardial damage. Due to its accuracy and
      diagnostic versatility, including intraprocedural use, Doppler echocardiography
      provides essential information for the planning and monitoring of non
      pharmacological therapy in patients with hypertrophic obstructive cardiomyopathy.

PMID- 16572986
TI  - [Administrative databases as a basic tool for the epidemiology of cardiovascular
      diseases].
AB  - The broader availability of administrative databases, characterized by increasing
      data reliability, related to the various steps of the healthcare process, has
      became also in Italy an important resource for epidemiological studies.
      Specifically, the methodological developments in the handling and analysis of
      drug prescription files can be seen as the original and highly informative
      backbone of a comprehensive monitoring of healthcare delivery processes. The area
      of chronic cardiovascular treatments occupies a privileged space in these
      developments, which are illustrated in the paper, with a synthetic presentation
      of the methodology supported by a model analysis of the epidemiology of heart
      failure in a healthcare district and by a reference list which has been conceived
      to provide to the reader a comprehensive perspective on an area so far largely
      unexplored.

PMID- 16572987
TI  - [Screening for abdominal aortic aneurysm during transthoracic echocardiography. A
      prospective study in 1202 consecutive patients at high risk: incidence,
      correlation with risk factors, feasibility, diagnostic accuracy, and increase in
      echocardiography time].
AB  - BACKGROUND: The rupture of abdominal aortic aneurysm is a pathology with a high
      mortality risk. Conversely, the study of the abdominal aorta is not routinely
      included in the echocardiography protocol, although it can be performed quickly
      and easily for screening of the aneurysm. The aim of this study was to evaluate
      screening of abdominal aortic aneurysm at the end of each echocardiographic exam
      performed at our laboratory. METHODS: From March 2002 to October 2003, 1202
      patients aged > 40 years were studied at our echo-lab. After the first 4 months
      of screening, only patients at high risk were screened, namely men > 65 or < 65
      years and women > 65 years with at least one risk factor for ischemic heart
      disease. We evaluated feasibility, diagnostic accuracy, incidence in the study
      population, interobserver variability, the correlation with risk factors for
      ischemic heart disease and the increase in total echocardiography time. RESULTS:
      The mean aortic diameter was 19.08 +/- 5.98 mm and feasibility was very high
      (95.6%). We found 62 unknown aneurysms and 20 localized aortic dilatations
      (incidence of 5.6 and 1.7%, respectively); the incidence of both of them was 9.1
      in men and 1.6 in women. Multivariate analysis revealed male gender, older age
      and other arterial district pathologies as independent risk factors. The
      interobserver concordance was excellent as well as diagnostic accuracy. The mean
      time increase in routine echocardiography was 33.8 +/- 18.6 s. CONCLUSIONS: The
      abdominal aortic study at the end of a routine echocardiography, in patients at
      risk of aortic pathology because of age or other risk factors, is a simple and
      accurate method for screening of abdominal aortic aneurysm. It showed a very low
      cost, also due to the short-time increase in routine echocardiography.

PMID- 16572988
TI  - [Sudden cardiac death: prevention when is right! From evidence-based medicine to
      family-based medicine].

PMID- 16572989
TI  - [Of defibrillators and guidelines].

PMID- 16572990
TI  - [Aortic pseudoaneurysm and aorta-right atrium fistula: a case report].
AB  - The development of an aortic pseudoaneurysm of the ascending aorta is described
      as a potential complication after composite graft surgery for combined disorders
      that simultaneously affect the aortic valve and ascending aorta; in the
      literature it has been reported to range from 7 to 25%. The aorta-right atrial
      fistula is an infrequent complication of aortic dissection and it is rarely
      diagnosed in association with aortic pseudoaneurysm. The pathophysiological
      mechanism of the first seems to be related to dehiscence of the suture line at
      the anastomosis site; in the second to anatomic contiguity between the aorta and
      right atrium. Our report refers to a 72-year-old man with a 3-year history of a
      Bentall composite aortic root replacement (modified by Kouchoukos), who presented
      with epigastric and chest pain accompanied with severe dyspnea. The diagnosis of
      aortic pseudoaneurysm complicated by right atrial fistula was made by the
      combination of transthoracic and transesophageal echocardiographic examination.

PMID- 16572991
TI  - [Research progress on chemical constituents of Laggera plants in China].
AB  - Laggera plants are traditionally used as folk medicine to treat bacterial
      infection, inflammation and fever in China. Three species, Laggera alata, L.
      intermedia and L. pterodonta, grow in China. Modem clinical studies show that L.
      pterodonta is a good medicine against inflammation. More than 100 compounds were
      obtained from these plants. In order to assist in medicinal application of this
      species of plants, progresses made in this field are systemically reviewed in
      this article.

PMID- 16572992
TI  - [The progress of the concentration technology of extract of traditional Chinese
      medicine].
AB  - The concentration of extract of traditional Chinese medicine (TCM) is one of the
      important unit operations that affect the quality of the pharmaceutical products.
      However, there are some problems to be solved. The concentration process has the
      shortages of relatively high temperature, relatively long time or low efficient,
      some losses of active and volatile ingredients, more operation steps, easy
      fouling and emission of waste water. In order to solve these problems, many new
      technologies and installations have been developed in the past thirty years,
      including suspension freeze-concentration, progressive freeze-concentration,
      single- or multi-effect evaporation with an external natural circulating flow, on
      line preventing fouling evaporation with vapor-liquid-solid flow, reverse osmosis
      concentration, membrane distillation, osmotic distillation, macro-porous resin
      adsorption etc. The system of the extract of TCM is very complex. The extract
      includes water and alcohol extracts. The composition of TCM is made of active and
      inactive ingredients. Hence, it is necessary to master the features of every
      concentration technologies and installations, including their merits and
      demerits, flexibilities, degree of maturations of techniques and so on to get a
      wise choice for the industry applications. New concentration technologies and
      installations of the extract of TCM developed recently are reviewed in this
      paper. The characteristics of each method are analyzed and discussed in order to
      guide the industry applications. At the same time, the further research
      directions of concentration techniques of extract of TCM are also given.

PMID- 16572993
TI  - [Synergistic effects of biotic and abiotic elicitors on the production of
      tanshinones in Salvia miltiorrhiza hairy root culture].
AB  - OBJECTIVE: To investigate the synergistic effects of a biotic elicitor yeast
      extract and different abiotic elicitors (Ag+, Co2+ and alpha-amino isobutyric
      acid) on the production of tanshinones in Salvia miltiorrhiza hairy root. METHOD:
      Different elicitors and their combinations were added to S. miltiorrhiza hairy
      root culture and the contents of three major tanshinones (crypotanshinone,
      tanshinone I and tanshinone II A) were analyzed by HPLC. RESULT: The combinations
      of yeast extract with different abiotic elicitors had notable synergistic effects
      on the tanshinone I and tanshinone II A production but not on crypotanshinone.
      The combination of yeast extract and Ag+ (300 micromol x L(-1)) yielded the
      highest tanshinone I content, which was nearly 14-fold of the control, and the
      synergistic elicitation coefficient was 3.0. The combination of yeast extract and
      Co2+ (100 micromol L(-1)) led to the highest tanshinone IIA content, which was
      about 14.5-fold of the control, and the synergistic elicitation coefficient was
      2.1. Only yeast extract combined with alpha-amino isobutyric acid (200 micromol x
      L(-1)) increased the crypotanshinone content more effectively than single
      elicitors. The highest crypotanshinone content was 1.28 mg x g(-1), about 30-fold
      of the control with a synergistic elicitation coefficient of 1.3. CONCLUSION: The
      elicitation by the combination of a biotic elicitor and an abiotic elicitor can
      generate a synergistic effect, which is more effective than single elicitors to
      promote secondary metabolite production in plant tissue cultures.

PMID- 16572994
TI  - [Standard operating procedure for Astragalus membranaceus].
AB  - In order to ensure the superior quality and safety of the raw materials of the
      Chinese herbal medicine, a standard operating procedure for astragalus was
      established on the base of the GAP of the Chinese herbal medicine as well as
      practice investigation and experiments. This standard operating procedure
      provides the technical requirements for astragalus's growing, field management,
      controlling of the diseases and pests, harvesting, processing, packing, storing,
      transporting and quality monitoring.

PMID- 16572995
TI  - [Determination of four components in root of Saposhnikovia divaricata by HPLC
      gradient elution].
AB  - OBJECTIVE: To develop an HPLC method for determination of components in root of
      Saposhnikovia divaricata. METHOD: The separation of four components was achieved
      on a reversed-phase Alltima C18 column with MeOH-H2O gradient elution at a flow
      rate of 1.0 mL x min(-1). RESULT: Six samples were determined and there is no
      distinct difference between the contents determined by the new and old methods.
      CONCLUSION: The new method is more simple and convenient than the old method.

PMID- 16572996
TI  - [Study on seed dormancy mechanisms of Changium smyrnioides and its geminating
      conditions].
AB  - OBJECTIVE: To study the seed dormancy mechanisms and the optimal seed germinating
      conditions, so as to provide basis for the seed testing of Changium smyrnioides.
      METHOD: Put the seeds into wettish sand under temperature of 25, 20, 15, 10, 5
      degrees C, observe the shape changing of embryo and measure its length every
      other 10 days. Carry on experiments of seed germination under temperature of
      25,20, 15, 10, 5 degrees C on the paper bed and sand bed, determine the time of
      germination starting, time of germination lasting, germination rate and
      germination energy. RESULT: Embryo grew the most quickly under 15 degrees C. The
      seed germination was largely prohibited when the temperature is higher than 20
      degrees C. The mildew rate was very high under 25, 20, 15, 10 degrees C. Put the
      seeds under 5 degrees C for 45 days could quickly break off its dormancy, and its
      mildew rate was lower. The seeds germinate fastest under the condition of 15-10
      degrees C on the paper bed, and its germination rate was the highest. CONCLUSION:
      The morphological post-maturation seems the major dormancy mechanism of C.
      smyrnioides. Temperature is a major factor that affect seed germination of C.
      smymioides. The best pretreatment method is to put the seeds into 5 degrees C of
      wettish sand for 45 days. The best germination bed is the paper bed, and the best
      germination temperature is 15-10 degrees C.

PMID- 16572997
TI  - [GC-MS analysis of the fatty components of pollen Typhae before and after being
      carbonized].
AB  - OBJECTIVE: To study the changes of the fatty components of Pollen Typhae before
      and after being carbonized. METHOD: Pollen Typhae and Pollen Typhae carbonisatus
      were extracted with petroleum ether (60-90 degrees C) respectively. The two kinds
      of extracts were analyzed by GC-MS after saponificated and methanolized, and
      their constituents were searched through NIST. The contents of the constituents
      were determined by method of normalization. RESULT: Either in Pollen Typhae or in
      Pollen Typhae carbonisatus, 32 components were identified, among which 20
      components were the same and 6 were different respectively. Among the same
      components, the relative contents of 3-methyl-2-butenoic acid-2-phenylethyl
      ester, hexanedioic acid-dimethyl ester, dimethyl phthalate, diethyl phthalate,
      diphenylamine, sebacic acid dimethyl ester, 1,2-benzenedicarboxylic acid, ethyl
      methyl ester, methyl-2-ethylhexyl phthalate and diisooctyl phthalate etc.
      increased obviously, and the relative contents of nonanedioic acid-dimethyl
      ester, diisobutyl phthalate and stigmastan-3,5-dien etc. decreased greatly. Among
      the different components, 8-hydroxy-octanoic acid-methyl ester, 9-hydroxy
      nonanoic acid-methyl ester, 10-octadecenoic acid-methyl ester, m-hydroxycinnamic
      acid-methyl ester,3-[4-( acetyloxy)-3-methoxyphenyl]2-propenoic acid-methyl ester
      and 11-octadecenoic acid-methyl ester were detected in Pollen Typhae, 3
      hydroxyspirost-8-en-11-one, benzenepropanoic acid-methyl ester, 2,4
      dimethylhexanedioic acid; 2,4-bis (1,1-dimethylethyl)-phenol, undecanedioic acid
      dimethyl ester and 9,10-dihydroxy-octadecanoic acid-methyl ester were detected in
      Pollen Typhae carbonistatus. CONCLUSION: The species and contents of the fatty
      components in Pollen Typhae changed before and after being carbonized, but their
      chemical types didn't change too much.

PMID- 16572998
TI  - [Simultaneous determination of resveratrol, emodin, chrysophanol, physcion, in
      root of Polygonam cuspidatum and its extract by HPLC].
AB  - OBJECTIVE: To establish a HPLC method for simultaneous determination of
      resveratrol, emodin, chrysophanol, physcion in root of Polygonum cuspidatum and
      its extract. METHOD: The separation was performed in a Hypersil ODS C18 column
      with a mobile phase of Acetonitrile-1%HAc. The flow rate was 1.0 mL x min(-1) and
      detection wavelength was at 287 nm. RESULT: The mean recovery and RSD of
      resveratrol, emodin, chrysophanol, physcion was 101.8%, RSD 1.7%; 96.2%, RSD
      1.4%; 99.7%, RSD 1.0%; 98.60%, RSD 0.97% respectively. CONCLUSION: The method is
      accurate, simple and reliable. It can be used for quality control of P.
      cuspidatum and its extract.

PMID- 16572999
TI  - [Study on the preparation of resveratrol chitosan nanoparticles with free amino
      groups on the surface].
AB  - OBJECTIVE: To prepare resveratrol chitosan nanoparticles with free amine groups
      on the surface so as to conjugate ligands, which will actively target to special
      tissues or organs. METHOD: The chitosan nanoparticles with free amine on the
      surface was prepared by sodium chloride precipitation. Nanoparticles with
      different solidification degrees were studied on turbidity, in vitro release,
      encapsulation efficiency, drug loading and diameter. RESULT: The turbidity of
      nanoparticles with various solidification degrees decreased at different rates
      after ultrasonic or water bath heating treatment. All nanoparticles mentioned
      above obviously shew sustained release. The rate of release was slowed down with
      the increase of solidification agents. Solidification had no obvious effects on
      the encapsulation efficiency and drug loading. The diameter of chitosan
      nanoparticles with 200 microL solidification agents was 487 nm. The
      polydispersion was 0.144. CONCLUSION: The diameter of the prepared nanoparticles
      was relatively small. The amine on the surface was free, which offered the
      possibility of designing the acive target drug delivery system.

PMID- 16573000
TI  - [Research on the influence of compatibility on fingerprint of Glycyrrhiza
      uralensis in mahuang decoctions by HPLC].
AB  - OBJECTIVE: To set up the HPLC fingerprint of Glycyrrhiza uralensis in decoctions
      prepared from various combinations of the recipe named Mahuang decoctions and
      study the influence of compatibility on fingerprint of G. wralensis in
      decoctions. METHOD: The RP-HPLC method was used, chromatography conditions were
      Zorbax SB-C18 column (4.6 mm x 250 mm, 5 microm), the acetonitrile-1.2% acetic
      acid (gradient elution) as mobile phase and detective wavelength at 254 nm.
      RESULT: The method is stable and reliable with a good reproducibility and
      provides a reference standard for the quality control of G. uralensis, it can be
      used to determine the fingerprint of G. aralensis in Mahuang decoctions. The
      result showed that 8 peaks were common in the fingerprint of G. uralensis in
      Mahauang decoctions. The area changes of 8 common peaks in decoctions prepared
      from various combinations of Mahuang decoctions were studied. CONCLUSION: The
      fingerprint of G. uralensis in Mahuang decoctions is markedly influenced by herba
      ephedrae and ramulus cinnamomi and semen armeniacae amarum. The areas of 7 common
      peaks were reduced obviously, while the relative areas of 6 common peaks were
      increased remarkably.

PMID- 16573001
TI  - [Isolation and structural elucidation of a bioactive saponin from tubers of
      Bolbostemma paniculatum].
AB  - OBJECTIVE: To study the bioactive constituents from tubers of Bolbostemma
      paniculatum. METHOD: Compounds were isolated by extraction and partition as well
      as several-chromatographic techniques guided with Pyricularia oryzae bioassay
      method. Their structures were determined on the basis of spectral analysis and
      chemical evidence. RESULT: Bisdesmoside (I) was isolated as active compound
      causing morphological abnormality of Pyncularia oryzae mycelia and elucidated as
      3-0-alpha-L-arabinopyranosyl (1-->2)-beta-D-glucopyranosyl-bayogenin-28-O-beta-D
      xylopyranosyl (1-->3)-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranoside.
      CONCLUSION: I is a new natural product and exhibited significant cytotoxicity
      against cancer cell lines K-562 and BEL-7402, but no hemolytic activity to rabbit
      erythrocytes.

PMID- 16573002
TI  - [Studies on chemical constituents of hairy root of Cassia obtusifolia].
AB  - OBJECTIVE: To study the chemical constituents in hairy roots of Cassia
      obtusifolia. METHOD: The hairy roots of C. obtusifolia were induced with
      Agrobacterium rhizogenes LBA9402 from cotyledons and cultured in MSO liquid
      medium. The compounds were isolated by silica gel, polyamide and Sephadex LH-20
      column chromatography, and the structures were elucidated by employing chemical
      and spectral methods RESULT: Eight compounds were isolated from the ethyl acetate
      fraction of 95% EtOH extract of the transformed roots of C. obtusifolia. They are
      betulinic acid, chrysophanol, physcion, stigmasterol, 1-hydroxy-7-methoxy-3
      methyl-anthraquinone, 8-O-methylchrysophanol, 1-O-methylchrysophanol and aloe
      emodin, and aloe-emodin was isolated from the hairy roots of C. obtusifolia for
      the first time. CONCLUSION: The hairy roots of C. obtusifolia have the ability to
      synthesize the similar chemical constituents as the original plants.

PMID- 16573003
TI  - [Liangge san effects the expression of CD14 and scaverger receptor in the Kupffer
      cells of liver of endotoxemia mice].
AB  - OBJECTIVE: To study the effects of Liangge San to the expression of CD14 and
      scaverger receptor(SR) in the kupffer cells of liver and the pathological changes
      of liver tissue of endotoxemia-mice. METHOD: The model was established with
      intravenous injection of lipopolysaccharide (LPS) and at the same time different
      dose Liangge San were given. The expression of CD14 and scaverger receptor were
      detected with immunohigtochemistry at the 2nd, 4th, 8th hour ofter injury and
      analyzed with computer image system, and the pathological changes of liver tissue
      were also observed. RESULT: At the three different hours, the expression of CD14
      and scaverger receptor in macrophages of liver of LPS-injury group showed
      significant increase and significant decrease respectively, compared with that of
      the blank-control group (P < 0.01). The expression in dexamethasone group and
      Liangge San different dose groups were intermediate between those in injury group
      and those in control group. Compared with expression of LPS-injury group, those
      of dexamethasone group and Liangge San different dose groups showed significant
      differences (P < 0.01), especially that of Liangge San high dose group. Liver
      cells showed vacuole change. Changes of CD14 and SR expression were paralleled
      with the severity of liver damages of the mice. CONCLUSION: Liangge San can
      inhibite the up-regulation of CD14 expression and down-regulation of scaverger
      receptor expression in a dosage-dependent manner and also alleviate the damages
      of liver induced by LPS.

PMID- 16573004
TI  - [Screening of glucosidase inhibitors from various fractions of Mulberry leaves].
AB  - OBJECTIVE: To search for glucosidase inhibitors of various fractions extracted
      from mulberry leaves. METHOD: The constituents of mulberry leaves water fraction
      were prepared by the process of boiling, condensing, precipitating, exchanging
      with resins and rinsing. In vitro glucosidase inhibitory activities were examined
      by photometric bioassay derived from rats. To investigate in vivo effect of
      lowering blood glucose, the mouse blood glucose level was assayed by glucose
      tolerance experiments. RESULT: The glucosidase inhibitory activities were found
      in all the constituents of alkaloids, flavones and amyloses, the alkaloid
      constituent being the strongest. CONCLUSION: The effect of reducing blood glucose
      of mulberry leaves is related to the inhibitory activities against glucosidase of
      different constituents.

PMID- 16573005
TI  - [Effects of Yifuning soft gelatin capsules on pathology and biomechanical indexes
      of ovariectomied rats].
AB  - OBJECTIVE: To study the effects of Yifuning soft gelatin capsules (YFN) on
      pathology and biomechanical indexes of ovariectomied female rats. METHOD: Sixty
      female Sprague-Dawley rats without pregnancy and delivery were used,50 of them
      were ovariectomized and randomly divided into 5 groups: ovariectomy(OVX), OVX
      with diethylstilbestrol tables (DT), OVX with YFN (high dose,middle dose and low
      dose), the others were sham-operated group. The rats began to take the rats drugs
      in the fifth week after the operation. After 12 weeks of treat ment the rats were
      killed, and the bones were collected to inspect. The pathology of bone was
      observed with the HE stain and the area of trabecular was detected. The
      electronic testing device was used to detect the biomechanical properties.
      RESULT: The results indicated that the rat model of postmenopausal osteoporosis
      (PMO) was a success. Compared with the model group, after application of the
      drugs, the observation of HE showed different repairing around trabecular. The
      biomechanical parameters also increased significantly. CONCLUSION: YFN can
      effectively prevent the loss of bone in OVX rats and strengthen bone quality, and
      has a good effect on PMO oostmenopausal osteoporosis.

PMID- 16573006
TI  - [Impact on the model of rat osteoarthritis of jingu tablet].
AB  - OBJECTIVE: To observe the influence of Jingu tablet (JGT) on the development and
      repair of osteoarthritis (OA). METHOD: The admixture of 4% papain and 0.3 mol x
      L(-1) cysteine was injected into the rat's knee joint to make the model of rat
      OA, and distilled water, Gucining Capsule and JGT was given ig simultaneously to
      treat for 4 weeks in succession, and then animals were killed to measure every
      index. RESULT: JGT could obviously improve the scope of activities of knee joint.
      There were significant differences between every dosage group and model group. In
      every dosage group, JGT could suppress the swelling of thickness of slippery
      membrane of joint, alleviate the inflammation symptoms of OA and obviouslical
      improve the pathologicol changes of slippery membrane and cartilage. JGT could
      also obviously reduce the content of MDA of slippery membrane and lighten the
      degree of cell damage. CONCLUSION: JGT can lighten the retrograde affection of
      joint cartilage, obviously suppress the slippery membrane's inflammation and
      alleviate the scathing degree of cell. Therefore JGT has definite remedial effect
      to OA.

PMID- 16573007
TI  - [Study on the proportion & mechanism of reliving asthma of drug partnership
      comprising herbal Ephedrae sinica & Pheretima aspergilum].
AB  - OBJECTIVE: To study the proportion and mechanism of relieving asthma of drug
      partnership comprising herbal Ephedrae & Pheretima. METHOD: To study relaxant
      effect on 10 micromol x L(-1) carbachol (CCh) and 10 micromol x L(-1) histamine
      (His) precontracted isolated tracheal rings and lowering effect on short-circuit
      current (Isc) increase induced by 10 micromol x L(-1) CCh with 3 proportions of
      1:1, 1:3, 1:9 extract. RESULT: 1:3 proportions dose-dependently relaxed CCh
      precontracted isolated tracheal rings, IC50 of 1:1, 1:3 is 7.5, 15 mg x mL(-1)
      respectively, 1:9 could not produce 50% inhibition effect on CCh-evoked
      contraction; 3 proportions also dose-dependently relaxed His-precontracted
      isolated tracheal rings, IC50 of 1:9, 1:3 and 1:1 is 0.19, 0.61, 1.8 mg x mL(-1)
      respectively. On the other hand,the orders potency of the decrease effect on CCh
      evoked short circuit current increase is 1:3 > 1:1 > 1:9. The difference is not
      significant (P < 0.05). CONCLUSION: Herbal Ephedrae & Pheretima had tracheal
      muscle relaxant and epithelium ion secretion inhibition effect, its mechanism of
      relieving asthma involved anti-CCh and anti-His effect 1:3 was the most
      appropriate dosage ratio in the anti-asthmatic drug partnership.

PMID- 16573008
TI  - [The anti-inflammation effects of Smilax china ethylacetate extract in rats and
      mice].
AB  - OBJECTIVE: To study the anti-inflammations of the ethyl acetate extract of S.
      china on acute and chronic inflammations. METHOD: The rat paw edema induced by
      egg-albumin, the ear edema and the foot edema of mice induced by xylene and
      formaldehyde, the increased vascular permeability of capillary induced by
      intraperitoneal injection of 0.7% acetic acid in mice were used to study on the
      acute, early inflammations and chronic inflammation for the ethyl acetate extract
      of S. china. RESULT: The extract (50-100 g x kg(-1)) could significantly decrease
      the rat paw edema, and inhibit the ear edema, the increased vascular permeability
      and the foot edema of mice. CONCLUSION: The ethyl acetate extract of S. china
      possesses remarkable anti-inflammatory effects on acute inflammation, and also
      displays anti-inflammatory effects on the chronic inflammation at a certain
      extent.

PMID- 16573009
TI  - [Effects of different concentration extract from shenghua decoction on
      contractile activity of the uterine smooth muscle isolated from normal, estrogen
      treated and postpartum mice].
AB  - OBJECTIVE: To investigate the effects of different concentration extract from
      Shenghua decoction on contractile activity of the uterine smooth muscle isolated
      from normal, estrogen-treated and postpartum mice. METHOD: Medlab/4 s vital
      signal recorder was used to measure the effects of extract from Shenghua
      decoction (3-12 mg x mL(-1)) on contractile amplitude and frequency of the
      isolated uterus from normal, estrogen-treated and postpartum mice. RESULT:
      Shenghua decoction extract (3-12 mg x mL(-1)) significantly decreased the
      contractile activity of the mouse isolated uterus in normal non-pregnancy and
      postpartum, but significantly increased that of the mouse isolated uterus treated
      with estrogen, and didn't show significant concentration-response relationship.
      CONCLUSION: The effects of Shenghua decoction extract on contractile activity of
      mouse-isolated uterus treated with estrogen cannot represent the pharmacological
      effects on that of in normal non-pregnancy and postpartum uterus.

PMID- 16573010
TI  - [Effects of compound Salvia injection on number and activity of endothelial
      progenitor cells].
AB  - OBJECTIVE: To investigate the effects of Compound Salvia injection (CSI) on the
      number and activity of endothelial progenitor cells (EPCs). METHOD: Mononuclear
      fraction of human umbilical cord blood was obtained by density gradient
      centrifugation and plated on fibronectin coated culture dishes. Cells were
      divided in to five groups: group control, group VEGF, group CSI 50, group CSI 10
      and group CSI 2 (supplemented with none cytokine, VEGF 10 ng x mL(-1), CSI 50,
      10, 2 microg x mL(-1), respectively). After six days in culture, cell clusters
      were viewed with an inverted microscope, fluorescence-activated cell sorting
      (FACS) analysis of PE-CD34 and FITC-VE-Cadherin was performed to detect number of
      EPCs, adhesion assay was performed by replating cells on fibronectin coated
      dishes, and then counting adherent cells. RESULT: Numbers of EPCs of group VEGF,
      group CSI 10 and group CSI 2 were significantly increased as compared with those
      of group control ( P < 0.01, P < 0.05, P < 0.01, respectively), and numbers of
      EPCs of group CSI 2 were more than those of group CSI 10 and group V (P < 0.01).
      Compared with group control, number of EPCs of group CSI 50 was significantly
      decreased (P < 0.01). Compared with group control, numbers of clusters and
      adhesive EPCs of group CSI 10 and group CSI 2 were significantly increased, while
      those of group CSI 50 were significantly decreased. CONCLUSION: Low concentration
      CSI can significantly promote EPCs augmentation and enhance its functional
      activity, while high concentration CSI significantly restrains it.

PMID- 16573011
TI  - The improving efficiency frontier of religious not-for-profit hospitals.
AB  - By using data-envelopment analysis (DEA), this study evaluates the efficiency of
      religious not-for-profit hospitals. Hospital executives, healthcare policy
      makers, taxpayers, and other stakeholders benefit from studies that improve
      hospital efficiency. Results indicate that overall efficiency in religious
      hospitals improved from 72% in 1998 to 74% in 2001. What is more important is
      that the number of religious hospitals operating on the efficiency frontier
      increased from 40 in 1998 to 47 in 2001. This clearly documents that religious
      hospitals are becoming more efficient in the management of resources. From a
      policy perspective, this study highlights the economic importance of encouraging
      increased efficiency throughout the healthcare industry.

PMID- 16573012
TI  - The role of organizational infrastructure in implementation of hospitals' quality
      improvement.
AB  - Quality improvement (QI) is an organized approach to planning and implementing
      continuous improvement in performance. Although QI holds promise for improving
      quality of care and patient safety, hospitals that adopt QI often struggle with
      its implementation. This article examines the role of organizational
      infrastructure in implementation of quality improvement practices and structures
      in hospitals. The authors focus specifically on four elements of hospital support
      and infrastructure for QI-integrated data systems, financial support for QI,
      clinical integration, and information system capability. These macrolevel factors
      provide consistent, ongoing support for the QI efforts of clinical teams engaging
      in direct patient care, thus promoting institutionalization of QI. Results from
      the multivariate analysis of 1997 survey data on 2350 hospitals provide strong
      support for the hypotheses. Results signal that organizations intent upon
      improving quality must attend to the context in which QI efforts are practiced,
      and that such efforts are unlikely to be effective unless appropriate support
      systems are in place to ensure full implementation.

PMID- 16573013
TI  - Forming design teams to develop healthcare information systems.
AB  - Healthcare information systems are assuming an increasingly critical role in
      providing quality patient care in an effective and efficient manner. However, the
      success of these systems in achieving these goals remains a lingering concern.
      Consequently, investigating and devising strategies to enhance the likelihood of
      success of a healthcare information system continues to draw research interest.
      One strategy recommended by both researchers and practitioners alike is the
      participation of the target users in the design and development of the
      information system. However, practical considerations mandate representative,
      rather than universal, participation of users. Unfortunately, the information
      systems literature offers few guidelines for selecting user representatives to
      serve on a design team. This lack of guidelines easily results in system
      designers talking with the wrong users or managers assigning the wrong users to
      the design team. On the basis of the theoretical paradigms underlying the user
      participation and design team concepts, the authors examined and derived user
      characteristics that are considered the most critical criteria for selecting user
      members of a design team. They then report on a field survey they conducted to
      validate the derived criteria in healthcare information systems context. The
      authors conclude that the system-related functional expertise should be the
      primary criterion employed to select healthcare personnel to participate in
      system design and development. Other criteria, such as users' communication
      skills, computing backgrounds, and personality traits, should be given secondary
      considerations. Ignoring these guidelines can render user participation
      superfluous, resulting in system failures.

PMID- 16573014
TI  - Beyond triage: avian flu and the impending services demand crisis.

PMID- 16573015
TI  - Dealing with pediatric patients--a commentary.

PMID- 16573016
TI  - Gloving revisited.

PMID- 16573017
TI  - Shove it.

PMID- 16573018
TI  - The ORBIS Flying Eye Hospital.

PMID- 16573019
TI  - Cryosurgery for prostate cancer.

PMID- 16573020
TI  - Nursing ethics in practice: issues for perioperative nursing.

PMID- 16573021
TI  - Setting up the role of emergency surgical nurse practitioner.

PMID- 16573022
TI  - Surgical gloves: perforation and protection.

PMID- 16573023
TI  - Esmarch's bandage.

PMID- 16573024
TI  - Periodic mesoporous organosilicas (PMOs): past, present, and future.
AB  - Periodic mesoporous organosilicas (PMOs) represent a new class of organic
      inorganic hybrid materials suitable for a broad range of applications such as
      chromatography, catalysis, sensing and microelectronics. Unlike in organic
      functionalized mesoporous silica phases obtained via grafting or co-condensation
      procedures the organic groups in PMOs are direct parts of the 3D framework
      structure, thus giving raise to enormous possibilities to tune their chemical and
      physical properties in designated ways by varying the structure of the
      precursors. In this review the distinctive features of PMOs are discussed, the
      latest developments concerning compositions, structures, morphologies and
      potential applications are figured out and finally a brief outlook of future
      aspects is given.

PMID- 16573025
TI  - Nanocomposites based on conducting polymers and carbon nanotubes: from fancy
      materials to functional applications.
AB  - This review deals with recent progress on the development of nanocomposite
      materials formed by conducting organic polymers (COPs) and carbon nanotubes
      (CNs), both from a fundamental and applied point of view. The combination of the
      unique properties of CNs with COPs makes of these materials interesting
      multifunctional systems with great potential in many applications such as
      supercapacitors, sensors, photovoltaic cells and photodiodes, optical limiting
      devices, solar cells, high-resolution printable conductor, electromagnetic
      absorbers, and, last but not least, advanced transistors.

PMID- 16573026
TI  - Organo-modified anionic clays into polymer compared to smectite-type nanofiller:
      potential applications of the nanocomposites.
AB  - The scope of the article is to provide the state of the art concerning the
      utilization of Layered Double Hydroxide (LDH) materials in polymer nanocomposite
      and to enlight their potential application and even advantage in comparison to
      smectite-type materials. A particular attention is paid on the synthetic
      procedures for the elaboration of polymer nanocomposite taking poly(styrene),
      poly(imide), poly(methylmethacrylate) and epoxy resin as examples.
      Lipophilization of the inorganic platelets used to decrease the surface polarity
      may be achieved either with a surfactant molecule or a surfactant monomer
      molecule, giving rise to reactive hybrid filler. The state of dispersion of the
      inorganic platelets, i.e., intercalated versus exfoliated structure is discussed.
      LDH-based nanocomposites present mechanical properties, such as the tensile
      modulus and elongation at break, always greater in comparison to virgin polymer,
      but also compete well with smectite-type filler. For epoxy nanocomposite, the
      relative gain using LDH nanofiller is superior to smectite-type filler. In both
      types of nanocomposites using either LDH or smectite-type nanofiller, mixed
      intercalated-exfoliated structure is generally met. Dispersion of LDH
      nanoplatelets should emerge well as flame-retardant materials and as polymer
      electrolyte, but may also find application in topical domains such as in sun
      radiation absorption.

PMID- 16573027
TI  - Multi-walled carbon nanotubes and metallic nanoparticles and their application in
      biomedicine.
AB  - Interdisciplinary research has become a matter of paramount importance for novel
      applications of nanomaterials in biology and medicine. As such, many disciplines
      physics, chemistry, microbiology, cell biology, and material science-all
      contribute to the design, synthesis and fabrication of functional and
      biocompatible devices at the nanometer scale. Since the most areas of cell
      biology and biomedicine deal with functional entities such as DNA and proteins,
      mimicry of these structures and function in the nanosize range offers exciting
      opportunities for the development of biosensors, biochips, and bioplatforms. In
      this report we highlight the potential benefits and challenges that arise in the
      manufacture of biocompatible nanoparticles and nano-networks that can be coupled
      with biological objects. Among the challenges facing us are those concerned with
      making the necessary advances in enabling affordability, innovation, and quality
      of manufactured nanodevices for rapid progress in the emerging field of bio
      nanotechnology. The convergence of nanotechnology and biomedicine makes nanoscale
      research highly promising for new discoveries that can cost-effectively
      accelerate progress in moving from basic research to practical prototypes and
      products.

PMID- 16573028
TI  - Comparing the mechanical properties of high performances polymer nanocomposites
      from biological sources.
AB  - There are numerous examples where animals or plants synthesize extracellular high
      performance skeletal biocomposites consisting of a matrix reinforced by fibrous
      biopolymers. Cellulose and chitin are classical examples of these reinforcing
      elements, which occur as whisker-like microfibrils that are biosynthesized and
      deposited in a continuous fashion. In many cases, this mode of biogenesis leads
      to crystalline microfibrils that are almost defect-free, with the consequence of
      axial physical properties approaching those of perfect crystals. Starch is
      another example of natural semicrystalline polymer that is produced by many
      plants and occurs as microscopic granules. It acts as a storage polymer in
      cereals and tubers. These abundant and natural polymers can be used to create
      high performance nanocomposites presenting outstanding properties. Aqueous
      suspensions of crystallites can be prepared by acid hydrolysis of the purified
      substrates. The object of this treatment is to dissolve away regions of low
      lateral order so that the water-insoluble, highly crystalline residue may be
      converted into a stable suspension by subsequent vigorous mechanical shearing
      action. For cellulose and chitin, these monocrystals appear as rod-like
      nanoparticles which dimensions depend on the biological source of the substrate.
      In the case of starch they consist of platelet-like nanoparticles. High
      reinforcing capability was reported resulting from the intrinsic chemical nature
      of these polymers and from their hierarchical structure. During the last decade,
      many works have been devoted to mimic biocomposites by blending cellulose
      whiskers from different sources with polymer matrices.

PMID- 16573029
TI  - Structural analysis of nanocomposites based on HDPE/EPDM blends.
AB  - Intercalated and exfoliated nanocomposites based on HDPE and EPDM blends with an
      organoclay have been obtained through the addition of EPDM-g-MA as a
      compatibilizer. The combined effect of clay and EPDM-g-MA on the rheological
      behaviour is very noticeable with a sensible increase in viscosity which suggests
      the formation of a structural net of percolation induced by the presence of
      intercalated and exfoliated silicate layer. As deduced from rheological studies,
      a morphology based on nanostructured micro-domains dispersed in HDPE continuous
      phase is proposed for EPDM/HDPE blend nanocomposites. XRD and SEM analysis
      suggest that two different transport phenomena take simultaneously place during
      the intercalation process in the melt. One due to diffusion of HDPE chains into
      the tactoid and the other to diffusion of EPDM-g-MA into the silicate galleries.

PMID- 16573030
TI  - Polyethylene organo-clay nanocomposites: the role of the interface chemistry on
      the extent of clay intercalation/exfoliation.
AB  - High density polyethylene (HDPE)/clay nanocomposites have been prepared using
      three different functionalized polyethylene compatibilizers: an ethylene/vinyl
      acetate copolymer, a polyethylene grafted with maleic anhydride functions and a
      (styrene-b-ethylene/butylene-b-styrene) block copolymer. The nanocomposites were
      prepared via two different routes: (1) the dispersion in HDPE of a masterbatch
      prepared from the compatibilizer and the clay or (2) the direct melt blending of
      the three components. For each compatibilizer, essentially intercalated
      nanocomposites were formed as determined by X-ray diffraction and transmission
      electron microscopy. With the ethylene/vinyl acetate copolymer, a significant
      delamination of the intercalated clay in thin stacks was observed. This
      dispersion of thin intercalated stacks within the polymer matrix allowed
      increasing significantly the stiffness and the flame resistance of the
      nanocomposite. A positive effect of shear rate and blending time has also been
      put into evidence, especially for the process based on the masterbatch
      preparation, improving both the formation of thin stacks of intercalated clay and
      the mechanical properties and the flame resistance of the formed nanocomposites.

PMID- 16573031
TI  - Nanostructure in hybrid thermosets with interpenetrating networks and its effect
      on properties.
AB  - Hybrid resins composed of vinylester (VE) and aliphatic amine (Al-Am)-cured
      cycloaliphatic epoxy (Cal-EP) were produced and their morphology and properties
      (toughness, water uptake) determined. According to atomic force microscopy (AFM)
      results achieved on physically etched (ion eroded) specimens the hybrid resins
      possessed a nanoscaled interpenetrating network (IPN) structure, the
      characteristics of which depended on the VE/EP ratio. Characteristics of the IPN
      morphology, viz strand width and mean roughness data increase with increasing
      amount of the EP component. The fracture mechanical data (K(Q) and G(Q)) pass a
      maximum as a function of the VE/EP ratio, similar to that of the phase
      segregation term (alpha). The latter was deduced from dynamic-mechanical thermal
      analysis (DMTA) traces. The water sorption and diffusion behavior of the
      interpenetrated VE/EP hybrids were controlled by the relative amount of the EP
      (Cal-EP+Al-Am) used.

PMID- 16573032
TI  - One-step synthesis and solvent-induced exfoliation of hybrid organic-inorganic
      phyllosilicate-like materials.
AB  - A room-temperature sol-gel-based process was used to produce by direct synthesis
      talc-like organosilicates having hexadecyl or aminopropyl groups pending in the
      interlayer space. Thermal analyses, Fourier transform infrared and 13C/29Si solid
      state nuclear magnetic resonance spectroscopies confirmed the presence of organic
      moieties bonded to the inorganic network. Exfoliation of these organoclays in
      polar solvents such as water for the positively charged magnesium
      phyllo(aminopropyl)silicate, and in low polar solvents such as toluene and
      chloroform for hydrophobic magnesium phyllo(hexadecyl)silicate, was investigated
      by TEM. The ability of these layered magnesium organosilicates to exfoliate in
      appropriate solvents was exploited for the preparation of transparent self
      supporting films and ordered macroporous networks using by latex colloidal
      crystal templates.

PMID- 16573033
TI  - Ormosil nanocomposite materials as modifiers for acrylic coating systems.
AB  - Organically modified silica (ormosil) particles were prepared using hydrolytic
      sol-gel methods and the miniemulsion polymerisation approach. Methyl-, ethyl-,
      and phenylsilsesquioxane nanoparticles with diameters in the range 50-180 nm were
      obtained using the modified Stober method with an aqueous sodium silicate
      solution used as a seed for further growth of the particles. Methyl- and
      phenylsilsesquioxane particles were prepared by a sol-gel method in the presence
      of benzethonium chloride used as a surfactant. The miniemulsion polymerisation
      approach has been extended to the production of methacrylate-modified silica
      nanoparticles with vinylpyridine or lauryl methacrylate used as comonomers both
      in the presence and in the absence of a surfactant. Styryl-modified silica
      particles with diameters in the range 300-800 nm were obtained by the Stober
      method using pre-formed SiO2 nanoparticles as the seeds for silsesquioxane
      nanoparticle formation. The effect of incorporation of the particles produced
      using different synthetic methods on hardness and water resistance of acrylic
      coating systems was studied here.

PMID- 16573034
TI  - Intrinsic photoluminescence from gels containing amine or amide chemical groups.
AB  - Gels obtained through the sol-gel procedure by mixing an alkoxide with a
      carboxylic acid emit intense intrinsic photoluminescence when the alkoxide
      contains an amine or amide group. However, also simple polyether chains with two
      end amino groups but no alkoxysilane groups gel by interaction with carboxylic
      acids and also emit photoluminescence. Luminescence emission in these gels could
      be justified by a model similar to the emission of Green Fluorescent Protein.
      According to this model, amide groups, abundant in these gels, go through
      multiple reactions with other amide or amino groups so that they could yield
      conjugated species that are capable to emit photoluminescence. This model could
      open the possibility to synthesize a great variety of photoluminescent species
      based on amine-carboxylate interactions.

PMID- 16573035
TI  - First direct synthesis of highly ordered bifunctionalized mesoporous silica thin
      films.
AB  - Optically transparent and highly ordered mesoporous organosilica thin films
      functionalized with two different organic groups in various proportions were
      synthesized by templated-directed cocondensation of tetraethylorthosilicate
      (TEOS) and a mixture of two distinct and functional organotriethoxysilanes
      [NC(CH2)3Si(OEt)3 and O=P(OEt)2(CH2)3Si(OEt)3]. The mesostructured films obtained
      by evaporation induced self-assembly (EISA) approach were deposited on glass or
      silicon substrates by dip-coating. They were characterized by Grazing Incidence
      Small Angle X-ray Scattering (GISAXS) and X-ray reflectivity. We showed that
      whatever the proportion in organic groups, only 2D hexagonal phase having p6m
      symmetry was observed for all the materials indicating a good compatibility
      between the organic groups. The bi-functionalization of the internal pores
      surface by the organotriethoxysilanes groups was clearly evidenced by using micro
      Raman spectroscopy.

PMID- 16573036
TI  - Structural studies of trimethoxysilane containing R'R"Im+I- ionic liquid and its
      nanocomposite with tetramethoxysilane (TMOS).
AB  - A dialkylsubstituted imidazolium iodide ionic liquid (1-methyl-3-[3-(trimethoxy
      lambda4-silyl)propyl]imida-zolium iodide, MTMSPIm+I-) was prepared with the
      intention of using it as a quasi-solid-state electrolyte for dye-sensitized
      photoelectrochemical (DSPEC) cells of Gratzel design, while the analogous
      electrolyte in a gel state was made by the addition of tetramethoxysilane (TMOS)
      in the molar ratio MTMSPIm+I-:TMOS = 1:1. The structure of the MTMSPIm+I- in its
      non-hydrolyzed and hydrolyzed states and in its fully condensed form, obtained
      after ageing the sols for various times (from a few hours to a few weeks) and
      heating them at 200 degrees C (fully condensed form), was studied employing time
      dependent infrared attenuated total reflection (ATR) and 29Si NMR spectroscopic
      measurements. The structure of the condensed species was correlated with the
      viscosity and the specific conductivity measurements of MTMSPIm+I- sols and
      TMOS/MTMSPIm+I- gels during their ageing. The final product of the condensation
      of MTMSPIm+I- sols was described as a positively-charged ladder-like
      polysilsesquioxane with Tn end groups exhibiting a single T3 signal in 29Si NMR
      spectra and characteristic doublet bands at 1138 and 1049 cm(-1) in IR. This
      structure was retained to a large extent in TMOS/MTMSPIm+I- gels, confirming
      their nanocomposite structure. The results of the ATR infrared time-dependent
      spectroscopic studies showed that in the course of condensation of sols, the
      refractive index of the modes attributed to the polysilsesquioxane species
      exhibited strong dispersion, which led to shifts in the vibrational band
      positions in the experimental ATR spectra. This effect accompanies the sol-to-gel
      transformations and has not yet been considered as a possible error in analysis
      of the ATR spectra of sols and gels. The calculation procedure for obtaining the
      corresponding transmission spectra is briefly outlined and the results applied in
      this work.

PMID- 16573037
TI  - Modified electrodes prepared from ferrocene functionalized silicate xerogels:
      analysis of the electrochemical response in isotropic and fractal structural
      systems.
AB  - New xerogels functionalized by ferrocenes as redox probes have been prepared
      using various types of catalysis. The analysis of the electrochemical response in
      the case of modified electrodes allows us to get an insight into the gel
      nanostructure which has been found to be isotropic in the case of acidic
      catalysis, and fractal in the case of fluoride catalysis, provided that the
      amount of functionalized silanes is not too high. Indeed the results of
      electrochemical measurement prove that the fractality of functionalized hybrid
      silica is general in the case of basic catalysis, except in the case of very high
      functional moieties loading, where the electrode become essentially organic and
      isotropic. On the other hand, in the case of acidic catalysis, whatever the
      amount of organic material, the hybrid gel remains isotropic, and a classical
      electron pseudo-diffusive behaviour is observed. The diffusion coefficient values
      extracted from the current-time slopes do not vary monotonically with the amount
      of redox probe in the case of fractal xerogel structures, which is indicative
      that not all the functional moieties are electroactive in that case.

PMID- 16573038
TI  - Synthesis of copper sulphide nanoparticles in carboxylic acids as solvent.
AB  - A novel method for the preparation of CuS nanoparticles based on the fast
      nucleation of the sulphide has been developed. The particles have been
      synthesized by reaction of thioacetic acid with water and copper carboxylates
      (acetate, propionate) in the corresponding carboxylic acid (acetic, propionic) as
      a solvent. The use of carboxylic acids presents several advantages: (i) the
      hydrolysis of the C-S bond is favoured thus producing a fast CuS supersaturation
      and a high nucleation rate; (ii) the mobility of the precursor molecules is
      limited so that nucleation events are favoured with respect to particle growth;
      (iii) the low dielectric constant of the medium stabilises the nanoparticles
      dispersion by reducing the critical coagulation concentration. The prepared
      nanoparticles were investigated by UV-Vis spectroscopy, X-ray photoelectron
      spectroscopy, atomic force microscopy and dynamic light scattering. The
      nanoparticle suspensions are clear and characterized by a blue-shifted adsorption
      edge with respect to bulk CuS. Light scattering measurements performed on acetic
      acid suspensions evidence the formation of monodispersed nanoparticles with an
      average diameter of about 5 nm.

PMID- 16573039
TI  - Integration of zinc oxide nanoparticles into transparent
      poly(butanediolmonoacrylate) via photopolymerisation.
AB  - A new method for the preparation of transparent ZnO/PBDMA nanocomposites (PBDMA =
      poly(butanediolmonoacrylate)) is reported. Zinc oxide nanocrystals (4-10 nm) were
      synthesized in ethanol and then transferred into butanediolmonoacrylate (BDMA) to
      obtain a transparent and stable colloidal suspension. No further growth or
      aggregation of the particles could be observed, after dispersing the particles in
      the monomer. Effective size control in the range of 6-10 nm and concentrations up
      to 10 wt% zinc oxide were demonstrated for these systems. The particles and
      suspensions were characterized by transmission electron microscopy, X-ray
      diffraction, UV-VIS spectroscopy and dynamic light scattering. The addition of
      trimethylolpropane triacrylate (TMPTA) and a photoinitiator to the ZnO/BDMA
      suspension lead to a UV-curable liquid. Photoinduced polymerization was used to
      produce transparent nanocomposites containing the nanoparticles. The material
      exhibits a strong UV absorption below 360 nm, a high transmission (90%) in the
      visible spectral range and a green photoluminescence.

PMID- 16573040
TI  - Synthesis of SiO2-coated Bi2S3/poly(styrene) nanocomposites by in-situ
      polymerization.
AB  - New nanocomposites containing silica-coated Bi2S3 nanofibers were synthesised by
      in situ polymerization using two distinct synthetic strategies: emulsion and
      suspension polymerization. Transmission and scanning electron microscopy of the
      nanocomposite particles showed that in both cases the Bi2S3/SiO2 nanoparticles
      were densely coated with poly(styrene). In situ emulsion polymerization afforded
      nanocomposites in which the nanofibers were coated with polymer spheres whilst
      suspension polymerization gives rise to a homogeneous polymer layer coat. The
      morphology of the poly(styrene) coating observed is discussed considering the
      surface modification of the nanofibers and the polymerization technique involved.

PMID- 16573041
TI  - Synthesis of polymer latex particles decorated with organically-modified laponite
      clay platelets via emulsion polymerization.
AB  - We report a new route to colloidal nanocomposites consisting of polymer latex
      particles covered with Laponite clay nanoplatelets. These composite particles are
      prepared by seeded emulsion (co)polymerization of styrene and butyl acrylate from
      Laponite clay suspensions previously functionalized by ion exchange using either
      a free radical initiator: 2,2-azobis (2-methylpropionamidine) hydrochloride
      (AIBA) or a cationic vinyl monomer: 2-(methacryloyloxy) ethyl trimethyl ammonium
      chloride (MADQUAT). The successful intercalation of the cationic reactive
      molecules was confirmed by elemental analysis, FTIR, 13C solid-state NMR and
      WAXD. The organically-modified clays were dispersed into water with the help of
      tetrasodium pyrophosphate and an anionic surfactant. stable latexes, produced
      under different experimental conditions, were successfully obtained from the clay
      suspensions. Cryo-TEM images of the resulting latexes showed spherical composite
      particles with diameters in the 50-250 nm range with clay sheets located on their
      surface. This paper reports on the effect of the processing conditions on the
      particle morphology and latex stability, and describes the mechanism of formation
      of the nanocomposite particles.

PMID- 16573042
TI  - Nucleation of polystyrene latex particles in the presence of gamma
      methacryloxypropyltrimethoxysilane: functionalized silica particles.
AB  - Silica/polystyrene nanocomposite particles with different morphologies were
      synthesized through emulsion polymerization of styrene in the presence of silica
      particles previously modified by gamma-methacryloxypropyltrimethoxysilane (MPS).
      Grafting of the silane molecule was performed by direct addition of MPS to the
      aqueous silica suspension in the presence of an anionic surfactant under basic
      conditions. The MPS grafting density on the silica surface was determined using
      the depletion method and plotted against the initial MPS concentration. The
      influence of the MPS grafting density, the silica particles size and
      concentration and the nature of the surfactant on the polymerization kinetics and
      the particles morphology was investigated. When the polymerization was performed
      in the presence of an anionic surfactant, transmission electron microscopy images
      showed the formation of polymer spheres around silica for MPS grafting densities
      lower than typically 1 micromole x m(-2) while the conversion versus time curves
      indicated a strong acceleration effect under such conditions. In contrast,
      polymerizations performed in the presence of a larger amount of MPS moieties or
      in the presence of a non ionic emulsifier resulted in the formation of
      "excentered" core-shell morphologies and lower polymerization rates. The paper
      identifies the parameters that allow to control particles morphology and
      polymerization kinetics and describes the mechanism of formation of the
      nanocomposite colloids.

PMID- 16573043
TI  - Synthesis of core-shell nanoparticles using organic surface-functionalized gold
      and Au@SiO2 nanoparticles as multifunctional initiators in atom transfer radical
      polymerization.
AB  - Gold and Au@SiO2 nanoparticles were synthesized and surface-functionalized by
      initiators for atom transfer radical polymerization (ATRP), either using a thiol
      or a trialkoxysilane anchor group for the immobilization of the initiating
      functionality. The thus obtained initiator-capped gold systems were applied in
      polymerizations of various monomers, such as styrene, methacrylic acid
      trimethyloxysilyl propylester and isoprene and copolymers thereof. The final
      inorganic-organic core-shell nanoparticles were characterized applying different
      techniques such as electron microscopy and light scattering. Kinetic studies of
      the polymerizations revealed that they were highly controlled and therefore the
      thickness of the polymer shell could be easily adjusted. The obtained
      nanoparticles formed stable suspensions in various organic solvents and can
      therefore be used as building blocks for polymer nanocomposites.

PMID- 16573044
TI  - Optically active poly(dimethylsiloxane) elastomer films through doping with gold
      nanoparticles.
AB  - Poly(dimethylsiloxane) (PDMS) elastomer films synthesized through a cross-linking
      reaction between hydroxyl-terminated or vinyl-terminated PDMS have been
      homogeneously doped with silica-coated Au nanoparticles. The nanocomposite
      synthesis involves mixing a preformed colloid of surface-modified metal
      nanoparticles with the elastomer film precursors. The homogeneous distribution of
      nanoparticles is demonstrated through the presence of well defined plasmon
      absorbance bands in the visible, which clearly show that the composites retain
      the characteristic optical properties of single Au nanoparticles. The metal
      particle concentration could be easily tailored either through the amount or the
      concentration of the nanoparticle colloid added. Since the Au nanoparticles are
      not cross-linked to the polymer and the concentration of particles is relatively
      low, we postulate that the presence of the nanoparticles does not affect the
      mechanical properties of the films, though this remains to be confirmed.

PMID- 16573045
TI  - Reversible photochromic properties of TiO2-polymer nanocomposites.
AB  - Composite films of nanosized TiO2 particles, which contained rutile as the only
      detected crystal modification, and poly(vinyl alcohol), poly(vinyl pyrrolidone)
      or poly(4-vinylpyridine) were prepared from aqueous dispersions. During exposure
      to UV irradiation the nanocomposites comprising poly(vinyl alcohol) or poly(vinyl
      pyrrolidone) turned blue as a consequence of a partial reduction of TiIV to
      TiIII. The color intensity increased with increasing TiO2 content and irradiation
      time. This color did not fade after removal of the UV source in spite of the
      sensitivity of TiIII to atmospheric oxygen. By contrast, exposure to water caused
      the nanocomposites to adopt their original colorless appearance. These
      colorization-decolorization cycles could be repeated more than 10 times without
      apparent loss of intensity. Due to the small size of the TiO2 nanoparticles (ca.
      3 nm), patterned blue structures of high resolution could be created in the
      polymeric materials, for instance with simple masking methods.

PMID- 16573046
TI  - Characterization and thermophysical properties of unsaturated polyester-layered
      silicate nanocomposites.
AB  - The thermophysical properties of unsaturated polyester (UPE) nanocomposites
      reinforced by organo-montmorillonite clay nanoplatelets are reported. The organo
      clay nanoplatelets were sonicated in acetone for 2 hours to be dispersed in the
      UPE matrix. Vacuum extraction removed not only the acetone but also the styrene
      present in the UPE solution. The same mechanical and thermophysical properties of
      UPE were regained after adding the lost amount of styrene to the UPE solution.
      Both delaminated and intercalated clay morphologies were observed by transmission
      electron microscopy. It was found that the sonication process was effective to
      delaminate clay nanoplatelets for more homogeneous dispersion, dependent on
      organic chemical modifications for clay nanoplatelets. A higher storage modulus
      enhancement was obtained when the organo-clay nanoplatelets were delaminated and
      more homogeneously dispersed. The reinforcing effect of both delaminated and
      intercalated clay nanoplatelets was theoretically evaluated with the Halpin-Tsai
      equations. It was evaluated that the aspect ratio of delaminated clay
      nanoplatelets was approximately 150. The increase of the storage modulus below
      and above the glass transition temperature was achieved without reducing glass
      transition temperature and Izod impact strength with increasing clay content.

PMID- 16573047
TI  - Phase separation of polystyrene/poly(vinylmethylether)/organoclay nanocomposites.
AB  - The effect of addition of organically modified montmorillonite (OMMT) on the
      phase separation of polystyrene (PS)/poly(vinyl methyl ether) (PVME) blend was
      examined. Using two types of OMMT modified with two different kinds of
      surfactants, the effect of organic modification on nanocomposites was
      investigated by focusing on three major aspects: phase transition, morphological
      study, and melt rheological behavior both below and above the critical transition
      temperature. X-ray diffraction (XRD) patterns revealed the formation of
      intercalated nanocomposites and transmission electron micrographic (TEM)
      observations showed that the ordering of silicate layers in blend matrix is well
      matched with the XRD patterns. The addition of clay was found to affect both the
      mechanism of phase separation and the final morphology. Such effects resulted in
      uncommon rheological behavior of the blend both below and above the critical
      transition temperature. Surface phase separation of thin films for virgin blend
      and nanocomposites was also examined by atomic force microscopy (AFM). Morphology
      resulting after phase separation was found to be dependent on the nature and the
      amount of OMMT added to the polymer blend.

PMID- 16573048
TI  - Effect of pre-strain on interfacial friction damping in carbon nanotube polymer
      composites.
AB  - This paper investigates the effect of mechanical pre-strain on interfacial
      friction damping in nanotube polymer composites. Oxidized single-walled carbon
      nanotubes were dispersed in a polycarbonate matrix using a solution mixing
      technique. To characterize the damping response, the material storage and loss
      modulus was measured by application of dynamic (sinusoidal) load to the
      nanocomposite in the uniaxial direction. A static pre-strain (in 0.35-0.85%
      range) was then superimposed on the dynamic strain to quantify its effect on the
      material response. The results indicate that application of pre-strain
      facilitates the activation of interfacial slip at the nanotube-polymer interfaces
      at relatively low dynamic strain amplitudes. This is because pre-strain raises
      the interfacial shear stress for the nanotube inclusions allowing the critical
      stress for tube-matrix interfacial slip to be reached at lower strain amplitudes.
      In this way pre-strain significantly improves the effectiveness of the nanotube
      matrix sliding energy dissipation mechanism for damping enhancement in composite
      structures.

PMID- 16573049
TI  - Electrospun bioactive nanocomposite scaffolds of polycaprolactone and
      nanohydroxyapatite for bone tissue engineering.
AB  - Nanocomposite scaffolds based on nanofibrous poly(epsilon-caprolactone) (PCL) and
      nanohydroxyapatite (nanoHA) with different compositions (wt%) were prepared by
      electrostatic co-spinning to mimic the nano-features of the natural extracellular
      matrix (ECM). NanoHA was found to be well dispersed in polymers up to the
      addition of 20 wt%, after ultrasonication. The composite scaffolds were
      characterized for structure and morphology using XRD, EDX, SEM, and DSC. The
      scaffolds have a porous nanofibrous morphology with fibers (majority) having
      diameters in the range of 450-650 nm, depending on composition, and
      interconnected pore structures. SEM, EDX, and XRD analyses have confirmed the
      presence of nanoHA in the fibers. As the nanoHA content in the fibers increases,
      the surface of fibers becomes rougher. The mechanical (tensile) property
      measurement of the electrospun composites reveals that as the nanoHA content
      increases, the ultimate strength increases from 1.68 MPa for pure PCL to 2.17,
      2.65, 3.91, and 5.49 MPa for PCL/nanoHA composites with the addition of 5, 10,
      15, and 20 wt% nanoHA, respectively. Similarly the tensile modulus also increases
      gradually from 6.12 MPa to 21.05 MPa with the increase of nanoHA content in the
      PCL/nanoHA fibers, revealing an increase in stiffness of the fibers due to the
      presence of HA. DSC analysis reveals that as nanoHA in the composite scaffolds
      increases, the melting point slightly increases due to the good dispersion and
      interface bonding between PCL and nanoHA.

PMID- 16573050
TI  - Effects of carbon nanotubes and metal catalysts on hydrogen storage in magnesium
      nanocomposites.
AB  - This paper reports a study on nanostructured magnesium composites with carbon
      nanotubes (CNTs) and catalytic transition metals with high H2 adsorption capacity
      and fast adsorption kinetics at reduced hydrogenation temperatures.
      Nanostructures in such a composite are shown to be responsible for improvements
      in both adsorption capacity and kinetics. It is found that the carbon nanotubes
      significantly increase the hydrogen storage capacity, and the catalytic
      transition metals (Fe and Ti) greatly improve the kinetics. This could be
      understood from the enhancement of diffusion by CNTs and decrease in energy
      barrier of hydrogen dissociation at the magnesium surface.

PMID- 16573051
TI  - High dielectric permittivity in silica-polyaniline nanocomposites.
AB  - Complex impedance and dielectric permittivity of wide band gap silica-conducting
      polyaniline nanocomposite have been investigated as a function of frequency and
      temperature at different compositions. Grain and grain boundary contributions are
      observed in impedance spectra. The results are interpreted in terms of two series
      connected equivalent circuit. The large dielectric permittivity approximately
      7500 is found. Large value of permittivity is well described by Maxwell-Wagner
      polarization. Broad and asymmetric dielectric spectra are analyzed by Havriliak
      Negami relaxation function.

PMID- 16573052
TI  - Nanofiber of ultra-structured aluminum and zirconium oxide hybrid.
AB  - An internally ultrastructured Al- and Zr-oxide hybrid was developed into a
      nanofiber. As a precursor for the generation of nanofiber, a hybridized sol was
      prepared using the Pechini-type sol-gel process, whereby the Al- and Zr-metallic
      ions were to be efficiently distributed and stabilized within the polymeric
      network. The hybridized sol was subsequently electrospun and heat treated to a
      nanofiber with diameters of tens to hundreds of nanometers. The internal
      structure of the nanofiber was organized at the molecular level, with the Al- and
      Zr-oxide regions being interspaced at distances of less than ten nanometers. This
      ultrastructured Al- and Zr-oxide hybrid nanofiber is considered to be potentially
      applicable in numerous fields.

PMID- 16573053
TI  - Deposition of gold nanoparticles on electrospun MgTiO3 ceramic nanofibers.
AB  - A simple method to deposit spherical gold nanoparticles on the surface of MgTiO3
      ceramic nanofibers is presented. Electrospun MgTiO3/poly(vinyl acetate) (PVAc)
      hybrid nanofibers were calcined at 650 degrees C to obtain phase pure ceramic
      MgTiO3 nanofibers with 100-150 nm diameters. These ceramic nanofibers were
      immersed in an aqueous solution of HAuCl4 containing poly(vinyl alcohol) (PVA) as
      capping agent followed by photoreduction at 365 nm to get a novel Au-MgTiO3
      nanocomposite. The formation of gold nanoparticles upon irradiation was confirmed
      by the appearance of a surface plasmon band (SPB) at 590 nm in the UV-visible
      absorption spectra. The surface morphology and elemental compositions were
      analyzed by the scanning electron microscope (SEM) equipped with energy
      dispersive X-ray (EDX), and transmission electron microscope (TEM). X-ray
      diffraction (XRD) and selected area diffraction (SAED) pattern in TEM revealed
      the crystallization of gold by exhibiting strong diffractions correspond to
      Au(111) and Au(200) crystalline planes in addition to the MgTiO3 diffraction.

PMID- 16573054
TI  - Novel bone scaffolds of electrospun polycaprolactone fibers filled with
      nanoparticles.
AB  - Novel bone scaffolding materials were successfully fabricated by electrospinning
      from polycaprolactone (PCL) solutions containing nanoparticles of calcium
      carbonate (CaCO3) or hydroxyapatite (HA). The potential use of the electrospun
      fibrous scaffolds for bone regeneration was evaluated in vitro with human
      osteoblasts (SaOS2) in terms of attachment, proliferation, and alkaline
      phosphatase (ALP) activity of the cells that were cultured directly on the
      scaffolds. The results were compared with those on corresponding solution-cast
      film scaffolds and tissue-culture polystyrene plate (TCPS). It was found that all
      of the fibrous scaffolds promoted much better adhesion and proliferation of cells
      than the corresponding film scaffolds and TCPS. Interestingly, the cells that
      were seeded on all of the fibrous scaffolds appeared to be well-expanded and
      attach on the fiber surface very well even only about 1 hr in culture, while
      those seeded on all of the film scaffolds and the glass substrate were still in
      round shape. Among the various fibrous scaffolds investigated, the one that was
      filled with 1.0% HA showed the highest ALP activity. Finally, all of the fibrous
      scaffolds exhibited much greater tensile strength at yield than all of the
      corresponding film scaffolds.

PMID- 16573055
TI  - Intercalation/Exfoliation mechanism of hybrid formation in polypropylene/lamellar
      mesostructured silica nanocomposites.
AB  - Understanding the optimal processing conditions for the fabrication of polymer
      nanocomposites is of fundamental importance in designing materials with balance
      of properties. To understand these conditions in the case of maleic anhydride
      grafted polypropylene (PP-g-MA)/layered mesostructured silica (LMS)
      nanocomposites, the effect of temperature, shear rate, and residence time during
      processing on the structure of the nanocomposites were studied. The results
      showed that the combination of temperature, residence time, and mechanical shears
      have strong effect on the structure of the nanocomposites, rather than just
      interfacial interactions between the polymer matrix and silicate layers. However,
      interfacial interactions between the polymer matrix and silicate layers primarily
      play an important role to the intercalation of polymer chains into the silicate
      galleries. On the basis of our experimental results, a first explanation of the
      formulation mechanism of PP-g-MA/LMS nanocomposites is proposed. Finally, a
      general concept of processing conditions for manufacturing of polymer
      nanocomposites by melt-compounding process in a batch-mixer is described.

PMID- 16573056
TI  - Polyethylene/clay nanocomposites prepared by polymerization compounding method.
AB  - A new technique for the preparation of high density polyethylene/clay
      nanocomposite, "polymerization compounding," is reported. This technique was
      based on the chemical anchoring of a Ziegler-Natta catalyst on organically
      modified clay surface containing an ammonium cation bearing primary hydroxyl
      groups. The polymerization of ethylene was initiated after adequate activation
      and the growing polyethylene chains are directly adsorbed on to the clay surface
      through the hydroxyl-functionalized surfactant. Finally, the nanocomposite was
      prepared by diluting polyethylene adsorbed clay in the high density polyethylene
      (HDPE) matrix using a batch mixer at 180 degrees C. The as-synthesized
      nanocomposite was typically characterized by X-ray diffraction (XRD) and
      transmission electron microscopy (TEM) that revealed the formation of
      intercalated nanocomposite. Tensile property measurements exhibit substantial
      increase in stiffness (approximately 50%) and strength (approximately 20%) of
      nanocomposite as compared to that of neat HDPE. Dynamic mechanical analysis under
      molten state revealed 25% increase in storage modulus when compared to that of
      neat HDPE.

PMID- 16573057
TI  - Growth of tungsten oxide nanorods with carbon caps.
AB  - Hybrid nanostructures consisting of tungsten oxide nanorods with mushroom-shaped
      carbon caps were grown on electrochemically etched tungsten tips by thermal
      chemical vapor deposition with methane and argon. These nanorods grow along the
      radial direction and are very straight and smooth. Electron microscopy revealed a
      dominant diameter and length of approximately 50 nm and approximately 0.6 microm,
      respectively. High-resolution transmission electron microscopy (HRTEM), and
      electron energy loss spectroscopy (EELS) revealed the presence of crystalline
      monoclinic W18O49 in the nanorods, and the cap was entirely amorphous carbon. A
      plausible growth mechanism involves the reduction of tungsten oxide WO3, present
      on the tungsten surface, by methane at 900 degrees C.

PMID- 16573058
TI  - Thermal degradation kinetics and morphology of natural rubber/silica
      nanocomposites.
AB  - A novel natural rubber/silica (NR/SiO2) nanocomposite with a SiO2 loading of 4
      wt% is developed by incorporating latex compounding with self-assembly
      techniques. The SiO2 nanoparticles are homogenously distributed throughout the NR
      matrix as spherical nano-clusters with an average size of 75 nm. In comparison
      with the host NR, the thermal resistance of the nanocomposite is significantly
      improved. The degradation temperatures (T), reaction activation energy (E), and
      reaction order (n) of the nanocomposite are markedly higher than those of the
      pure NR, due to significant retardant effect of the SiO2 nanoparticles.

PMID- 16573059
TI  - Preparation, characterization and anion exchange properties of polypyrrole/carbon
      nanotube nanocomposites.
AB  - In this study, polypyrrole (PPy) thin films were electrodeposited on carbon
      nanotube (CNT) backbones by applying a constant deposition potential in 0.1 M
      pyrrole solution with different electrolytes, such as NaCl, NaNO3, or NaClO4. The
      hybrid films were characterized by scanning electron microscopy (SEM), X-ray
      photoelectron spectroscopy, and cyclic voltammetry. SEM images revealed the
      nanostructrure of PPy films generated on CNT surface. The electrochemical and
      anion exchange properties of the PPy-CNT composite films have been investigated.
      Nanostructured composite thin films of PPy-CNTs were studied by cyclic
      voltammetry between 0.4 and -0.8 V in aqueous solution to evaluate their cycling
      stability and capacity for electrically switched anion exchange. The presence of
      the CNT backbone greatly improved the anion exchange capacity and stability of
      the PPy-CNT composite film, which may be attributed to the high surface area of
      CNT matrix, nanostructure of the PPy film, and the interaction between CNTs and
      PPy.

PMID- 16573060
TI  - Synthesis of anatase-silver nanocomposite fibers via electrospinning.
AB  - There has been growing interest in new ways to produce composite nanofibers.
      Continuous TiO2 (anatase phase) nanofibers with silver nanoparticles were
      prepared successfully via sol-gel and electrospinning. A sol containing
      poly(vinyl pyrrolidone), titanium tetraisopropoxide, and silver nitrate was
      injected through a conductive capillary where high voltage was applied. As a
      result of electrospinning, continuous composite nanofibers were collected and
      they were calcined in air at 500 degrees C in order to complete the
      crystallization of anatase phase. The anatase-silver nanocomposite fibers were
      characterized with X-ray diffraction, field emission scanning electron
      microscopy, high resolution transmission electron microscopy, and energy
      dispersive X-ray spectroscopy.

PMID- 16573061
TI  - Novel growth of aluminium nitride nanowires.
AB  - This work describes novel growth of aluminium nitride (AIN) nanowires by
      nitridation of a mixture consists of aluminium and ammonium chloride powders
      (Al:NH4Cl = 1.5:1 weight ratio) at 1000 degrees C for 1 h in flowing nitrogen gas
      (1 l/min). XRD analysis of the product showed the formation of pure hexagonal
      AIN. SEM micrographs of as-synthesized product revealed the growth of homogeneous
      AIN nanowires (phi 40-150 nm). No droplets were observed at the tips of obtained
      nanowires which suggests that they were grown mainly by a vapor-phase reactions
      mechanism. Thermodynamic analysis of possible intermediate reactions in the
      operating temperatures range illustrates that these nanowires could be grown via
      spontaneous vapor-phase chlorination-nitridation sequences.

PMID- 16573062
TI  - Metal-based nanoparticle synthesis from the rapid expansion of carbon dioxide
      solutions.
AB  - Synthesis of 10 to 500 nm diameter Fe-based nanoparticles is described. Nanometer
      sized droplets of iron carbonyl are generated by the rapid expansion of CO2-based
      supercritical fluid solutions and are photolyzed in-flight using a UV lamp to
      remove the carbonyl groups. Solid metal particles are collected electrostatically
      as coatings or loose particle aggregates on solid surfaces. Upon air oxidation,
      the iron particles react rapidly to produce an iron oxide phase. Mo-based
      nanoparticles were similarly produced using a Mo(Co)6 precursor. FTIR analysis of
      collected nanoparticles suggests that carbonyl groups are more readily photolyzed
      from the Fe precursor than from the Mo analog.

PMID- 16573063
TI  - Synthesis and characterization of stable iron-iron oxide core-shell nanoclusters
      for environmental applications.
AB  - Iron-iron oxide core-shell nanoclusters are of great interest due to their
      potential applications as a remedy for environmental contamination. We report the
      room-temperature synthesis of core-shell iron-iron oxide nanoclusters using our
      novel cluster deposition system. Various types of measurements such as
      Transmission Electron Microscopy, X-ray Diffraction, X-ray Photon Spectroscopy,
      and Electron Energy Loss Spectroscopy are conducted in characterizing
      nanoclusters. Stable, monodispersive iron-iron oxide core-shell nanocrystals are
      identified.

PMID- 16573064
TI  - Nanomaterials for lithium-ion rechargeable batteries.
AB  - In lithium-ion batteries, nanocrystalline intermetallic alloys, nanosized
      composite materials, carbon nanotubes, and nanosized transition-metal oxides are
      all promising new anode materials, while nanosized LiCoO2, LiFePO4, LiMn2O4, and
      LiMn2O4 show higher capacity and better cycle life as cathode materials than
      their usual larger-particle equivalents. The addition of nanosized metal-oxide
      powders to polymer electrolyte improves the performance of the polymer
      electrolyte for all solid-state lithium rechargeable batteries. To meet the
      challenge of global warming, a new generation of lithium rechargeable batteries
      with excellent safety, reliability, and cycling life is needed, i.e., not only
      for applications in consumer electronics, but especially for clean energy storage
      and for use in hybrid electric vehicles and aerospace. Nanomaterials and
      nanotechnologies can lead to a new generation of lithium secondary batteries. The
      aim of this paper is to review the recent developments on nanomaterials and
      nanotechniques used for anode, cathode, and electrolyte materials, the impact of
      nanomaterials on the performance of lithium batteries, and the modes of action of
      the nanomaterials in lithium rechargeable batteries.

PMID- 16573065
TI  - Soluble carbon nanotubes and their applications.
AB  - Carbon nanotubes (CNTs) have been the forefront of nanoscience and nanotechnology
      due to their unique electrical and mechanical properties and specific functions.
      However, due to their poor solubility in solvents, the applications using the
      materials have been limited. Therefore, strategic approaches toward the
      solubilization of CNTs are important in wide fields including chemistry, physics,
      biochemistry, biology, pharmaceuticals, and medical sciences. In this article, we
      summarize: (i) the strategic approaches toward the solubilization of CNTs using
      chemical and physical modifications, (ii) nanocomposites of CNTs and biological
      molecules including DNA, (iii) formation of CNTs with topological structures,
      (iv) separation of metallic and semiconducting nanotubes, (v) the preparations of
      films and fibers of CNTs and hybrid materials of CNTs and organic and inorganic
      molecules.

PMID- 16573066
TI  - A silicon-based, sequential coat-and-etch process to fabricate nearly perfect
      substrate surfaces.
AB  - For many thin-film applications substrate imperfections such as particles, pits,
      scratches, and general roughness, can nucleate film defects which can severely
      detract from the coating's performance. Previously we developed a coat-and-etch
      process, termed the ion beam thin film planarization process, to planarize
      substrate particles up to approximately 70 nm in diameter. The process relied on
      normal incidence etching; however, such a process induces defects nucleated by
      substrate pits to grow much larger. We have since developed a coat-and-etch
      process to planarize approximately 70 nm deep by 70 nm wide substrate pits; it
      relies on etching at an off-normal incidence angle, i.e., an angle of
      approximately 470 degrees from the substrate normal. However, a disadvantage of
      this pit smoothing process is that it induces defects nucleated by substrate
      particles to grow larger. Combining elements from both processes we have been
      able to develop a silicon-based, coat-and-etch process to successfully planarize
      approximately 70 nm substrate particles and pits simultaneously to at or below 1
      nm in height; this value is important for applications such as extreme
      ultraviolet lithography (EUVL) masks. The coat-and-etch process has an added
      ability to significantly reduce high-spatial frequency roughness, rendering a
      nearly perfect substrate surface.

PMID- 16573067
TI  - Structural and morphological changes of monolayers of a block copolymer with
      dendron and perfluoroalkyl side chains by mixing a perfluorooctadecanoic acid.
AB  - Hybrid Langmuir and Langmuir-Blodgett monolayers of a perfluorooctadecanoic acid
      mixed with a rigid block copolymer, poly(3,5-bis(3,5
      bis(benzyloxy)benzyloxy)benzyl methacrylate-randommethacrylic acid)-block-poly(2
      perfluorooctylethyl acrylate), which is composed of benzyloxy dendron side chains
      and perfluorinated side chains, were prepared and characterized by surface
      pressure-surface area isotherms, atomic force microscopic images and neutron and
      X-ray reflectometries. The two-dimensionally phase-separated structures of
      monolayer films and their morphologies with plateau and terrace were confirmed.
      The monolayers were separated into a dendron layer, a perfluorinated layer, and a
      carboxyl layer. The layer formation is originated not only in the intermolecular
      interaction between a perfluorooctadecanoic acid and a block copolymer but also
      in the geometry of the molecules. Especially, the amphiphilicity of
      perfluorinated surfactant plays a role to the ordered array of the block
      copolymers.

PMID- 16573068
TI  - Novel silicon-carbon fullerene-like nanostructures: an Ab initio study on the
      stability of Si54C6 and Si60C6 clusters.
AB  - Silicon fullerene like nanostructures with six carbon atoms on the surface of
      Si60 cages by substitution, as well as inside the cage at various symmetry
      orientations have been studied within the generalized gradient approximation to
      density functional theory. Full geometry optimizations have been performed
      without any symmetry constraints using the Gaussian 03 suite of programs and the
      LANL2DZ basis set. Thus, for the silicon atom, the Hay-Wadt pseudopotential with
      the associated basis set are used for the core electrons and the valence
      electrons, respectively. For the carbon atom, the Dunning/Huzinaga double zeta
      basis set is employed. Electronic and geometric properties of the nanostructures
      are presented and discussed in detail. It was found that optimized silicon-carbon
      fullerene like nanostructures have increased stability compared to bare Si60 cage
      and the stability depends on the orientation of carbon atoms, as well as on the
      nature of bonding between silicon and carbon atoms and also on the carbon-carbon
      bonding.

PMID- 16573069
TI  - Static and dynamic properties of single-walled boron nitride nanotubes.
AB  - This paper reports the study of the static and dynamic properties of single
      walled boron nitride nanotubes by using the molecular structural mechanics
      approach. The stiffness parameters of the boron-nitride bond are based on the
      DREIDING force field. The effects of tube diameter and chirality are
      investigated. The computational results show that the Young's modulus and the
      shear modulus of boron nitride nanotubes increase monotonically with nanotube
      diameter and reach up to 0.9 TPa and 0.5 TPa, respectively, at large tube
      diameter. The nanotube chirality has only slight effects on the moduli only when
      tube diameters are small. The fundamental frequencies of boron nitride nanotubes
      are found to be dependent not only on the nanotube aspect ratio but also on the
      tube diameter.

PMID- 16573070
TI  - Imaging nanometer scale optical heterogeneities in phospholipid monolayers
      deposited on metal island films.
AB  - Near-field scanning optical microscopy was applied to study the distribution of
      fluorescently labeled phospholipid monolayers deposited on the surface of gold
      island films by the Langmuir-Blodgett technique. Nanometer scale (approximately
      50 nm) optical heterogeneities were observed in near-field fluorescence images of
      the monolayer deposited at 10 mN/m surface pressure. At higher surface pressure
      (30 mN/m) the heterogeneities became less pronounced. Overlaying of the near
      field transmission and fluorescence images from the same area of the sample shows
      local transmission of gold island film is at a minimum where the fluorescence of
      the lipid monolayer is at a maximum. It was concluded that coverage of the metal
      island film by the Langmuir-Blodgett phospholipid monolayer is incomplete, and
      lipid molecules are preferentially localized in crevices of the film.

PMID- 16573071
TI  - Time-resolved fluorescence detection of mosaic DNA chip.
AB  - We demonstrated a time-resolved fluorescence (TRF) label and detection of mosaic
      DNA chip in this paper. We synthesized oligonucleotide sequences in situ on glass
      slides directly, and then sliced them up into small pieces and patched up the
      pieces bearing different sequences to generate a mosaic DNA chip. With multiple
      4, 7-bis(chlorosulfophenyl)-1, 10-phenanthroline-2, 9-dicarboxylic acid (BCPDA,
      abbreviated as BCPDA) labeling method based on avidin-biotin amplification, we
      established a TRF detection format on the mosaic DNA chip. The detection method
      allows discriminatory signals for perfect match, one-base mismatch, two-base
      mismatch, and three-base mismatch by TRF labeled DNA hybridization, whereby
      Europium (III, Eu3+) was captured and released on the principle of complexation
      and dissociation interaction between BCPDA and Eu3+ solution when the BCPDA
      tagged avidin and biotin-capped oligonucleotide sequence linked. The fluorescence
      spectra and related lifetimes were determined. We also compared the TRF detection
      mode with the conventional fluorescence one. These results showed the former is a
      potential alternative replacement of the latter, especially for labeling the
      mosaic DNA chip. The discovery is of fundamental interest and has significant
      implications to biochips and biosensors based on time-resolved-fluorescence
      detection.

PMID- 16573072
TI  - Fabrication of an atomic resolution low cost STM-SNOM hybrid probe.
AB  - We derived a simple method to fabricate STM-SNOM hybrid probes obtained from
      commercial cheap communication optical fibers. The tips are fabricated by a
      methodology that combines two well-known techniques: the selective attack by a
      buffered solution and the protected layer chemical etching, in a single new one
      step technique. The tailored probes are then sputtered by metal and mounted on a
      STM setup. The usual difficulties of integrating the optical fiber in the STM
      head are solved originally with a particular home made mount described in
      details. We will show that the resulting probes reach atomic resolution on both
      vertical and horizontal scale, and that the optical imaging is free of artifacts
      and satisfactory with a lateral resolution in the order of lamda/20, as far as we
      know the finest resolution obtained with a system based on a hybrid fiber probe.
      We believe that our methodology is very interesting for its simplicity of
      realization and for the good resolving power in both SNOM and STM modes.

PMID- 16573073
TI  - Nickel oxide nanotubes: synthesis and electrochemical performance for use in
      lithium ion batteries.
AB  - Uniform and aligned Nickel Oxide (NiO) nanotube bundles have been synthesized by
      a template process. Individual nanotubes are 60 microm long with a 200 nm outer
      diameter and wall thickness of 20-30 nm. The synthesis involved forming Ni(OH)2
      nanotubes that were subsequently heated to 350 degrees C in order to fully
      convert the product to NiO nanotubes. NiO nanotube powder was used in lithium-ion
      cells for assessment of lithium storage ability and electrochemical performance.
      Discharge capacity of the NiO nanotube electrode was in excess of 30% higher than
      that of the standard NiO nanocrystalline powder electrode after 20 cycles.
      Impedance data suggests the NiO nanotube electrode provides more controlled and
      sustainable Li diffusion when compared to the NiO reference powder electrode
      system.

PMID- 16573074
TI  - Filling of carbon nanotubes with selenium by vapor phase process.
AB  - A vapor phase method was developed to fill different kinds of nanotubes
      (including multiwall and singlewall nanotubes), which inner diameters range from
      200 down to 1.5 nm. Experiments were performed with selenium in a sealed reactor
      in order to control the selenium partial pressure. This process allows a full
      control of the nanotube filling (partial or complete), i.e., either a selective
      diameter filling or a full filling rate. The weight gain of all the samples was
      plotted for different reaction temperature as a function of selenium pressure.
      Experimental isotherms are characteristic of capillary condensation of selenium,
      which occurs at first in the smallest nanotube inner diameters. X-ray diffraction
      data show that selenium confined in nanotubes with diameters larger than 3 nm
      keeps its trigonal structure.

PMID- 16573075
TI  - Hydrogen storage in carbon nanotubes: a multi-scale theoretical study.
AB  - A Combination of quantum and classical calculations has been performed to
      investigate the hydrogen storage in single-walled carbon nanotubes (SWNTs). The
      ab-initio calculations at the Density Functional level of Theory (DFT) show the
      nature of hydrogen interaction in selected sites of a (5,5) tube walls. On top of
      this, Molecular Dynamics simulations model large scale nanotube systems and
      reproduce the storage capacity under variant temperature conditions. Our results
      indicate that the interaction of hydrogen with SWNTs is very weak and slightly
      increase of temperature, causes hydrogen diffusion from the tube walls.

PMID- 16573076
TI  - Study on the binding of procaine hydrochloride to DNA/DNA bases and the effect of
      CdS nanoparticles on the binding behavior.
AB  - The interaction between procaine hydrochloride and DNA/DNA bases in the absence
      and presence of cadmium sulfide (CdS) nanoparticles has been explored in this
      study by using differential pulse voltammetry, atomic force microscopy (AFM) and
      so on, which illustrates the different binding behaviors of procaine
      hydrochloride with different DNA bases. The results clearly indicate that the
      binding of purines to procaine hydrochloride is stronger than that of pyrimidines
      and the binding affinity is in the order of G > A > T > C. In addition, it was
      observed that the presence of CdS nanoparticles could remarkably enhance the
      probing sensitivity for the interaction between procaine hydrochloride and
      DNA/DNA bases. Furthermore, AFM study illustrates that procaine hydrochloride can
      bind to some specific sites of DNA chains, which indicates that procaine
      hydrochloride may interact with some special sequences of DNA.

PMID- 16573077
TI  - Assembly of hybrid oligonucleotide modified gold (Au) and alloy nanoparticles
      building blocks.
AB  - The alloy-based hybrid materials with macroscopic network arrays were developed
      by AuAg/Au and AuAgPd/Au nanoparticle composites through oligonucleotides
      hybridization. AuAg/Au and AuAgPd/Au exhibited distinct organization. The
      morphology of AuAg/Au conjugation assembled mainly as compact aggregates while
      AuAgPd/Au hybrid conjugated into the loosen network assemblies. The
      dehybridization temperatures were studied as a function of molar ratio of
      alloy/Au. It was found that higher alloy/gold molar ratio led to stronger
      hybridization for alloy/gold composite, accompanied with increased melting
      temperature. These results could be interpreted in terms of more alloy
      nanoparticles bound to a Au particle when the molar ratio of alloy/gold
      increased. The thermal analysis also showed that AuAg/Au exhibited higher
      dehybridization temperature. A modified model describing the dehybridization
      probability of an intact Au/alloy aggregate was performed to support the
      dehybridization temperature increased with increasing alloy/Au molar ratio. As to
      more oligonucleotides carried by AuAg (4.9 +/- 1.9 nm) than by AuAgPd (4.4 +/-
      1.5 nm) due to larger size in AuAg, the efficient hybridization could result in
      higher dehybridization temperature in AuAg/Au.

PMID- 16573078
TI  - Pyramidal nanostructures of zinc oxide.
AB  - Zinc oxide (ZnO) nanostructures have been prepared by pulsed laser deposition of
      the oxide onto Si(100) substrate at 600 degrees C. An examination of the
      morphology using atomic force microscopy and scanning electron microscopy reveals
      well formed pyramidal structures consistent with the growth habit of ZnO. A
      domain matched epitaxy across the interface makes the ZnO pyramids orient along
      the axes of Si(100) surface. The pyramidal nanostructures signify an intermediate
      state in the growth of hexagonal nanorods of ZnO. The hardness of the
      nanostructures as well as their response to oxygen gas have been investigated
      using nanoindentation and conducting probe methods respectively. ZnO
      nanostructures are much harder than their bulk. The hardness of ZnO pyramids
      obtained by nanoindentation is 70 +/- 10 GPa which is about one order more that
      of bulk ZnO. Besides, the nanostructures exhibit high sensitivity towards oxygen.
      A 70% increase in the resistance of ZnO nanostructures is observed when exposed
      to oxygen atmosphere.

PMID- 16573079
TI  - Structural transition in nanostructured Eu2O3 under high pressures.
AB  - We report here studies on the effect of high pressure on the structural
      properties of nano-sized Europium sesquioxide (Eu2O3) up to a pressure of about
      16.4 GPa. At ambient conditions, the starting sample was found to be
      predominantly cubic type Eu2O3 or in Eu3+ state with a trace of Eu2+. The
      presence of Eu2+ state is assumed to be arising due to the non-stoichiometric
      Eu(1-x)O phase which is obtained from XPS studies by the deconvolution of the Eu
      3d-core levels. The Raman studies at ambient show a strong peak at about 333 cm(
      1), which is known to occur due to the Fg mode of cubic Eu2O3 and in a similar
      way, the XRD data shows major peaks corresponding to the cubic phase of Eu2O3. A
      Mao-Bell type diamond anvil cell (DAC) was used to generate high pressures for
      XRD and Raman spectroscopy studies. It was observed that the material undergoes a
      structural change from cubic to monoclinic structure with an on set transition
      pressure at around 2 GPa and completes at around 8 GPa. This has been inferred
      from the fact that above about 2.0 GPa pressure, Raman studies show the emergence
      of a new peak corresponding to the monoclinic phase which increases in intensity
      and shifts further with increase in pressure, while the XRD studies show that
      above about 2.0 GPa, the peaks corresponding to monoclinic phase emerge, which
      show a slight increase in preferred orientation as the pressure is increased. A
      detailed discussion has been provided to explain this fact.

PMID- 16573080
TI  - Magnetic and catalytic properties of Cu0.5Zn0.5Fe2O4 nanocrystallite powders.
AB  - Cu0.5Zn0.5Fe2O4 nanocrystallite powders (average size 13 nm) were synthesized
      from Cu-Zn spent catalyst (fertilizers) industries and ferrous sulfate wastes
      formed during iron and steel making. Cu-Zn catalyst (22.4% Cu and 26.4% Zn) was
      chemically treated with sulfuric acid at temperature 80 degrees C for 1 hr for
      the complete dissolving of copper and zinc into sulfate solution, then the
      produced solution was mixed with stoichiometric ratio of ferrous sulfate and the
      mixture was chemically precipitated as hydroxides followed by hydrothermal
      processing. The parameters affecting the magnetic properties and crystallite size
      of the produced ferrites powder e.g., temperature, time, and pH were systemically
      studied. X-ray diffraction analysis was used in order to determine the average
      crystallite size and phase identifications of the produced powder. The magnetic
      properties were studied by vibrating sample magnetometry. The results showed that
      the average crystallite size of the powder decreased for the ferrites powder
      formed at 150 degrees C and then increased by increasing the temperature to 200
      degrees C. Interestingly, the saturation magnetization (Bs), remanent
      magnetization (Br) and coercive force (Hc) were 25.03 emu/g, 0.71 emu/g, and 4.83
      Oe, respectively at hydrothermal temperature 150 degrees C for 24 hr and changed
      to 16.38 emu/g, 0.3864 emu/g, and 5.2 Oe at 150 degrees C and 72 hr. The produced
      nanoferrite powders are used for studying the catalytic activity of CO conversion
      to CO2 at different temperatures, pH and times. The maximum conversion (82%) is
      obtained at temperature 150 degrees C for 24 hrs and pH 12.

PMID- 16573081
TI  - Synthesis and photoluminescence of Y2O3:RE3+ (RE=Eu, Tb, Dy) porous nanotubes
      templated by carbon nanotubes.
AB  - Y2O3:RE3+(RE=Eu, Tb, Dy) porous nanotubes were first synthesized using carbon
      nanotubes as template. The morphology of the coated precursors and porous
      Y2O3:Eu3+ nanotubes was determined by scanning electron Microscopy (SEM) and
      transmission electron microscopy (TEM). It was found that the coating of
      precursors on carbon nanotubes (CNTs) is continuous and the thickness is about 15
      nm, after calcinated, the Y2O3:Eu3+ nanotubes are porous with the diameter size
      in the range of 50-80 nm and the length in micrometer scale. X-ray diffraction
      (XRD) patterns confirmed that the samples are cubic phase Y2O3 and the
      photoluminescence studies showed that the porous rare earth ions doped nanotubes
      possess characteristic emission of Eu3+, Tb3+, and Dy3+. This method may also
      provide a novel approach to produce other inorganic porous nanotubes used in
      catalyst and sensors.

PMID- 16573082
TI  - Fabrication of aligned poly (vinyl alcohol) nanofibers by electrospinning.
AB  - Electrospinning has become a versatile tool for fabricating nanofibers from
      materials of diverse origins. Normally, mats of randomly-aligned fibers were
      obtained. A number of techniques have been proposed to arrive at uniaxially
      aligned fibers. This work reports a new technique, i.e., dual vertical wire
      technique, for fabrication of uniaxially-aligned fibers. This technique utilized
      two stainless steel wires that were vertically set in a parallel manner between a
      charged needle and a grounded collector plate. This technique allowed
      simultaneous collection of aligned fibers (between the parallel vertical wires)
      and a randomly-aligned fiber mat (on the collector plate). Application of the
      technique on poly(vinyl alcohol) (PVA) to prepare uniaxially-aligned fibers was
      found to be successful at short collection times. Unexpected formation of a large
      fiber tow consisting of individual as-spun nanofibers that were bound into a
      bundle was observed at long collection times. Morphological appearance and size
      of the fiber tow was affected by the change in the distance between the two
      vertical wire electrodes, while the average diameter of the individual fibers was
      not (i.e., about 340 to 350 nm). Lastly, mechanical properties and thermal
      behavior of the fiber tow were also investigated.

PMID- 16573083
TI  - Self-healing and self-organized gold nanoparticle films at a water/organic
      solvent interface.
AB  - Gold nanoparticles (5 nm and 20 nm) have been synthesized and stabilized with
      mercaptoundecanol. These particles, although insoluble in water or common organic
      solvents, spread as a thin film at the liquid-liquid interface between a water
      phase and an organic phase. Films of these gold nanoparticles have been observed
      both by conventional transmission electron microscopy of deposited samples and by
      cryo-transmission electron microscopy of plunge-frozen samples. The film can be
      monolayered and extend over centimeter-sized areas. The particle films
      spontaneously re-assemble and self-organize at the interface when disrupted. This
      self-healing capacity of the film should make it possible to build a device for
      continuous production and deposition of the film.

PMID- 16573084
TI  - Electron spin resonance and raman scattering spectroscopy of multi-walled carbon
      nanotubes: a function of acid treatment.
AB  - We compare the fundamental transport mechanism in multi-walled carbon nanotubes
      (MWNTs) by means of electron spin resonance (ESR) and Raman spectroscopy as a
      function of acid treatment. The ESR and Raman results show that the acid
      treatment reduces the density of states at the Fermi level. Defects introduced
      through the acid treatment move the Fermi level closer to the K points in the
      valence band, and consequently conduction is reduced. These defects are
      identified as Stone-Wales type from the Raman results.

PMID- 16573085
TI  - Various conformations of carbon nanocoils prepared by supported Ni-Fe/molecular
      sieve catalyst.
AB  - The carbon nanocoils with various kinds of conformations were prepared by the
      catalytic pyrolysis of acetylene using the Ni metal catalyst supported on
      molecular Sieves which was prepared using Fe-containing kaolin as the raw
      material. There are four kinds of carbon nanocoils conformations produced by this
      catalyst. The influences of reaction temperature and gas conditions on the
      conformations of the nanocoils were investigated and the reasons of forming nano
      size coils were discussed by comparison with pure Ni metal catalyst.

PMID- 16573086
TI  - Reactive gas condensation synthesis of aluminum nitride nanoparticles.
AB  - Aluminum Nitride (AIN) nanoparticles were synthesized using a Reactive Gas
      Condensation (RGC) technique in which a mixture of ammonia (NH3) and nitrogen
      (N2) gases were used for the nitridation of aluminum. NH3 served as the reactive
      gas, while N2 served as both a carrier gas and the inert source for particle
      condensation. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS)
      analyses revealed that at reactive gas compositions greater than 10% NH3 in N2,
      samples were composed entirely of hexagonal AIN nanoparticles. Electron
      diffraction patterns showed single crystal hexagonal AIN structure. The particle
      size was controlled by varying the pressure of the gas mixture. AIN nanoparticles
      were dispersed in a liquid matrix to enhance thermal conductivity. Results showed
      that a minimal addition of AIN increased the thermal conductivity of hydrocarbon
      pump oil by approximately 27%. The thermal conductivity became constant after
      reaching a maximum above 0.01 wt% AIN. Temporal stability of AIN was studied by
      XRD. Samples exposed to air for extended periods of time and analyzed by XRD show
      no degradation of crystalline AIN nanoparticles.

PMID- 16573087
TI  - Synthesis and characterization of Mn quantum dots by bioreduction with water
      hyacinth.
AB  - The bio-reduction method is reported as a part of a complimentary self-sustained
      technology, where bioremediation and metal particle production are related. The
      use of the characterization methods in this self sustainable technique open the
      expectative to be used for several other elements and with other plants, which
      will be discussed. However, the particular case of Mn nanoparticles involves an
      important option to generate nanoparticles in the range of 1-4 nanometers with a
      well controlled size and with a structure based on an fcc-like geometry for the
      smallest clusters and with more complex arrays for cluster greater than four
      shells, which involves magnetic moments significantly related to their atomistic
      configuration. At the same time, the use of the characterization methods
      establishes the dependence of the nanoparticle's size on the pH conditions used
      during the synthesis; small clusters in the range of 1-2 nm were generated using
      pH=5, and it was shown that for the smallest aggregates, simple polyhedron shapes
      are stable.

PMID- 16573088
TI  - Sonochemical fabrication and characterization of ceria (CeO2) nanowires.
AB  - Ceria (CeO2) nanowires have been successfully synthesized by a sonochemical
      method in ambient air and alkali aqueous solution from CeO2 nanoparticles without
      using any templates. The results showed that both alkali concentration and
      ultrasonic irradiation played critical roles in the formation of the nanowires.
      The crystalline structure and dimensions of the nanowires were characterized by
      powder X-ray diffraction (XRD), transmission electron microscopy (TEM), high
      resolution transmission electron microscopy (HRTEM) and selected area electron
      diffraction (SAED). The UV-visible absorption spectrum result showed that the
      products had conspicuous shape-specific effect. Microstructural analysis in HRTEM
      revealed that the preferential growth direction of CeO2 nanowires was [110].
      Moreover, the catalytic activity of Au/CeO2 using CeO2 nanowires as support for
      CO conversion was higher than that obtained using bulk CeO2 as support.

PMID- 16573089
TI  - Soft-template synthesis of single-crystalline CdS dendrites.
AB  - The single-crystalline CdS dendrites have been fabricated from the reaction of
      CdCl2 and thiourea at 180 degrees C, in which glycine was employed as a soft
      template. The obtained products were explored by X-ray diffraction, scanning
      electron microscopy, transmission electron microscopy, and selected area
      electronic diffraction. The optical properties of CdS dendrites have been
      investigated by ultraviolet and visible light (UV-vis) and photoluminescence
      techniques. The investigations indicated that the dendrites were grown due to the
      anisotropic properties enhanced by the use of Glycine in the route.

PMID- 16573090
TI  - A new hydrothermal route for synthesis of molybdenum disulphide nanorods and
      related nanostructures.
AB  - A simple approach to prepare nanorods of Molybdenum Disulphide (MoS2) using
      hydrothermal method by reacting aqueous solutions of (NH4)6Mo7O24.4H20, C2H4NS
      and Na2S2O4 at 190 degrees C for 24 h is described. The hydrothermal product has
      been subsequently subjected to the thermal treatment in nitrogen atmosphere at
      675 degrees C for 6 h and characterized. X-ray diffraction (XRD) of the
      hydrothermal product indicated the formation of MoS2 relatively with much lower
      crystallinity compared to when it thermally treated. Energy dispersive analysis
      (EDX) was done to know the chemical composition of the product. TEM showed onset
      growth of MoS2 nanorods within the hydrothermal products itself and in thermally
      treated products it was prominent with the diameter of the nanorods ranging
      between 10-20 nm. Photoluminescence spectra MoS2 nanorods shows an intense
      absorbance at around 429 nm. TGA of the MoS2 nanorods in air and nitrogen
      atmosphere has also been studied. The extent of formation of MoS2 from the
      precursors obtained at 190 degrees C for duration of 12, 18, and 24 h and
      annealed at 675 degrees C for 6 h under nitrogen atmosphere is also demonstrated
      based on XRD data.

PMID- 16573091
TI  - Microwave-assisted synthesis of pt nanocrystals and deposition on carbon
      nanotubes in ionic liquids.
AB  - In this work, a simple, fast and efficient route is presented for the metal (such
      as Pt, Rh, etc.) nanocrystal synthesis and deposition on carbon nanotubes (CNTs)
      in ionic liquids (ILs) via microwave heating. In this method, inorganic salts
      (such as H2PtCl6.4H2O, RhCl3.2H2O, etc.) dissolved in ILs, 1,1,3,3
      tetramethylguanidinium trifluoroacetate or 1,1,3,3-tetramethylguanidinium
      lactate, were reduced to metal nanoparticles by glycol with the aid of microwave
      heating, and the produced metal nanoparticles could be decorated on CNTs in the
      presence of CNTs in ILs. The resulting nanomaterials were characterized by means
      of transmission electron microscopy and X-ray diffraction. It was demonstrated
      that the homogeneously dispersed Pt nanocrystals with the size of 2-3 nm were
      obtained using H2PtCl6.4H2O as precursor, and they deposited on CNTs with the
      similar size when CNTs was present in ILs. This technique also can be extended to
      fabricate other noble metal nanocrystals (including Rh, Au, etc.) and
      corresponding CNT composites.

PMID- 16573092
TI  - Preparation and characterization of titania/ZnS core-shell nanotubes.
AB  - Core-shell nanocomposites of titania nanotubes/ZnS quantum dots have been
      prepared by using a hydrothermal synthetic method and characterized by using
      various microscopic and spectroscopic methods. ZnS quantum dots surround the
      outsides of titania nanotubes having the inner and the outer diameters of 15 and
      30 nm, respectively, with a thickness of 2 nm. The nanocomposites suspended in
      water show a broader absorption spectrum shifted to a longer wavelength by 20 nm
      and emit substantially stronger ZnS luminescence having significantly slower
      decay kinetics than bare ZnS nanoparticles in water. The support of TiO2
      nanotubes is found to enhance the optical properties of ZnS considerably.

PMID- 16573093
TI  - One-step preparation of MgO hollow spheres and hexagonal cylinders via Zn
      template.
AB  - Polycrystalline hollow spheres and single crystalline hexagonal cylinders of MgO
      have been fabricated by chemical vapor deposition using ZnO and Mg as the
      starting materials. The Zn produced during the chemical reaction serves as
      template material, and vaporization of which leads to the formation of the hollow
      structures. The presence of trace amount of Si in the source material is
      identified to be critical for the existence of the stable MgO hollow structures,
      which otherwise would be damaged during the Zn template removal process. The same
      principle can be readily adopted in many other material systems and result a
      variety of hollow structures for catalyst, sensor and medical applications.

PMID- 16573094
TI  - Numerical analysis on a passive chaotic micromixer with helical microchannel.
AB  - In order to improve the mixing efficiency, the diffusion and mixing of species in
      the helical micro-mixer are simulated numerically. The results show that the
      mixing efficiency in the helical micromixer is much higher than that in the
      straight micro-channel and obviously higher than that in the serpentine micro
      channel when Reynolds number is low. At high Reynolds number, even though the
      mixing efficiency in the helical micro-mixer is still much higher than that in
      the straight micro-channel, no obvious difference of mixing efficiency in the
      helical micro-mixer and serpentine micro-channel is found. The conclusions are
      helpful to optimize the structure of the micro-mixer.

PMID- 16573095
TI  - Enhancement of green electroluminescence from nanocrystalline silicon by wet and
      dry processes.
AB  - Correlation between defects and luminescence property from electroluminescent
      (EL) device composed of nanocrystalline silicon (nc-Si) prepared by wet and dry
      processes such as hydrofluoric (HF) acid solution treatment and annealing have
      investigated using electron spin resonance and EL measurements. The EL device
      using HF-treated nc-Si emitted strong red light, because of existence of only
      P'ce-centers (radiative recombination centers) on the surface vicinity. On the
      other hand, the EL device using annealed nc-Si above 400 degrees C exhibited
      green luminescence by the reduction of particle size due to surface oxidation.
      When the annealing temperature was risen from 400 degrees C up to 600 degrees C,
      the green luminescence strengthened with increasing the P'ce-centers. These
      results indicate that the formation of many radiative recombination centers onto
      the nc-Si surface vicinity lead to the enhancement of green luminescence from the
      nc-Si based EL device.

PMID- 16573096
TI  - Influence of oxidized layer on operating voltage and luminance of nanocrystalline
      silicon electroluminescent device.
AB  - A direct current (DC) operating voltage and luminescence property of red
      electroluminescent (EL) devices with and/or without a silicon dioxide (SiO2)
      layer at interface between nanocrystalline Si (nc-Si) region and Si substrate has
      investigated. The removal of SiO2 layer in the EL device led to the lowering of
      DC operating voltage from 4.0 up to 2.0 V and the increase of luminescence
      intensity more than one order of magnitude. The external quantum efficiency of
      red luminescence from the EL device without the SiO2 layer at the DC operating
      voltage of 3.0 V was 0.5%. These were realized by the efficient and easy
      injection of carriers to the radiative recombination centers in the nc-Si region
      due to the removal of SiO2 layer. These results indicate that the removal of SiO2
      layer is drastically improved the DC operating voltage and luminescence intensity
      for the nc-Si based EL device.

PMID- 16573097
TI  - Nanocrystalline ceria powders through citrate-nitrate combustion.
AB  - Nanocrystalline ceria powders have been synthesized by combustion technique using
      citric acid as a fuel and nitrate as an oxidizer. The auto-ignition of the gels
      containing cerium nitrate and citric acid resulted in ceria powders. A theory
      based on adiabatic flame temperature for different citric acid-to-cerium nitrate
      molar ratios has been proposed to explain the nature of combustion reaction and
      its correlation with the powder characteristics. Specific surface area and
      primary particle size of the ceria powder obtained through fuel-deficient
      precursor was found to be approximately = 127 m2/g and 2.5-10 nm, respectively.
      The combustion synthesized ceria powder when cold pressed and sintered in air at
      1250 degrees C for 1 hour resulted in approximately = 96% of its theoretical
      density with sub-micron grains.

PMID- 16573098
TI  - A rapid and facile method for hydrothermal synthesis of CdTe nanocrystals under
      mild conditions.
AB  - By using a novel procedure, a new kind of water-soluble CdTe nanocrystals (NCs)
      is synthesized in aqueous solutions at the temperature of 100 degrees C. In this
      procedure, tripeptide thiol glutathione was used as stabilizing agent, CdTe NCs
      with controllable photoluminescence wavelength from 500 nm to 680 nm were
      prepared within two hours. Compared with CdTe NCs prepared with thiohydracrylic
      acid as stabilizing agent, as-prepared NCs show much narrower photoluminescence
      FWHM, more symmetrical emission peak and higher photoluminescence quantum yield.
      The surface structure of as-prepared CdTe NCs is deduced, therefore, there may be
      some unreported circular structure on the surface. Experimental results show that
      as-prepared NCs have very good biological compatibility and they are nontoxic.
      And these CdTe NCs can conjugate with biological molecules for further biological
      luminescence study. The proposed hydrothermal synthesis procedure has the
      advantage of simplicity, inexpensiveness, time saving and mild operating
      conditions.

PMID- 16573099
TI  - A new method to synthesize nickel carbide (Ni3C) nanoparticles in solution.
AB  - Pure nickel carbide (Ni3C) nanoparticles with particle diameters of 40 nm have
      been prepared by thermal decomposition of nickel formate in the presence of oleic
      acid and oleyl amine. The coexistence of active nickel and active carbon plays an
      important role in the formation of metastable Ni3C. Ni3C powder decomposes at 770
      K in an N2 atmosphere to yield nickel and carbon. While in an H2 atmosphere, Ni3C
      powder is converted into Ni at 627 K. In addition, Ni3C nanoparticles exhibit
      superparamagnetism and are easier to magnetize at room temperature due to their
      good crystallinity and few defects.

PMID- 16573100
TI  - Synthesis of polyaniline nanofibrous networks with the aid of an amphiphilic
      ionic liquid.
AB  - In this work, polyaniline (PANI) nanofibrous networks were prepared using ionic
      liquid (IL), 1-hexadecyl-3-methylimidazolium chloride (C16MIMCl), as a template
      through oxidative polymerization of aniline with ammonium persulfate. The
      resulting PANI was characterized by means of scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), UV-vis, and FTIR. It was indicated that
      the as-prepared PANI was in the emeraldine form and its morphology strongly
      depended on the molar ratio of aniline/C16MIMCI. A possible mechanism for the
      formation of PANI nanofibrous networks was that the ordered micro-domains of the
      IL acted as template to direct the growth of the nanostructures.

PMID- 16573101
TI  - Large-scale synthesis of single crystal silver nanowires by a sodium
      diphenylamine sulfonate reduction process.
AB  - Silver nanowires with high aspect ratios of up to more than 60 were synthesized
      on a large scale by the redox reaction between silver nitrate and sodium
      diphenylamine sulfonate at room temperature and in the absence of surfactant and
      hard-template and seed. When the molar ratio of reductant sodium diphenylamine
      sulfonate and silver nitrate < or =1, most products were all the nanowires. When
      the molar ratio increases to 2:1, silver nanowires and nanobelts were
      concomitantly formed. The redox product N, N'-diphenylbenzidinedisulfonate and
      sodium diphenylamine sulfonate all play an important role in the formation of
      silver nanostructures. The structure, morphology, and composition of the silver
      nanowires were characterized by the X-ray powder diffraction (XRD), transmission
      electron microscopy (TEM), scanning electron microscopy (SEM), X-ray energy
      dispersive microanalysis (EDX), and UV-Vis spectroscopy respectively. High
      resolution transmission microscopy (HRTEM) and selected area electron diffraction
      (SAED) reveal the single-crystal nature of the silver nanowires.

PMID- 16573102
TI  - Synthesis and characterization of indium xanthates and their use for the
      preparation of beta-In2S3 nanoparticles.
AB  - Synthesis and characterization of various classical indium xanthate complexes of
      the type [InCl(3-n)(S2COR)n] (n = 1, 2, or 3; R = Me, Et, Pr(i), and Bu(s)) have
      been discussed. Crystalline beta-ln2S3 nanoparticles were obtained by the solvent
      thermolysis of indium tris-alkylxanthates in ethylene glycol at 196 degrees C,
      and were characterized by elemental analysis, IR, powder XRD, and XPS techniques.
      TEM results showed that the size of beta-In2S3 nanoparticles depended on the
      nature of the precursor used. The optical properties of beta-In2S3 nanocrystals
      have shown quantum confinement of the excitonic transition.

PMID- 16573103
TI  - Capacity of nano-reactors of AOT micro-emulsions to form and sustain ultra small
      semiconductor quantum dots.
AB  - Microemulsions (MEs) are increasingly being used as nano-reactors for the
      formation and synthesis of nanoparticles or quantum dots (QDs). In this paper, we
      study the capacity of aqueous nanoreactors of AOT microemulsions for the
      formation of ultrasmall semiconductor QDs by fixing w = ([H2O]/[AOT]) and varying
      the concentration of CdS up to 100 mM. The CdS QDs in the MEs are evaluated using
      UV-vis spectroscopy, XRD, TEM, and light scattering. Particles are found to be
      controlled in 8.7 A-11.8 A. The UV-vis spectra are analysed using an accurate
      tight-binding (TB) approach and effective mass approximation (EMA). The TB
      method, being much more accurate than the EMA, gives results in good agreement
      with X-ray diffraction (XRD) and transmission electron microscopy (TEM). XRD
      reveals that the particles are mostly zinc-blend at low concentrations (> or =20
      mM) but a mixture of zinc-blend and wurtzite at higher concentrations (100 mM).
      High concentrations of CdS are useful to improve the yield while best-utilizing
      nanoreactors and to give a tight control over size and polydispersity. MEs
      containing CdS are found to be stable over a month when kept in the dark.

PMID- 16573104
TI  - Solvothermal preparation and gas sensing properties of ZnO whiskers.
AB  - ZnO whiskers were prepared by a solvothermal process with Zn(OH)4(2-),
      cetyltrimethylammonium bromide (CTAB), n-amyl alcohol and n-hexane at 140 degrees
      C. The influence of preparation condition on the morphology of the resultant
      sample was investigated through change zinc salts, co-surfactants, surfactants,
      reaction temperature, and reaction time. Experimental results revealed that the
      morphology of as-obtained ZnO was affected strongly by the zinc salts and
      surfactants. The samples were characterized by X-ray diffraction (XRD), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), and electron
      diffraction (ED). Results showed that ZnO whiskers had the diameters of 100-500
      nm, the lengths of several microm, and grown along orientation of [0001]. The gas
      sensitivities of the as-prepared ZnO whiskers were detected. The results revealed
      that the ZnO whiskers had excellent potential application for gas sensor.

PMID- 16573105
TI  - Nanopowders of metallic oxides prepared by the hydrolytic route with starch
      stabilization and biological abetment.
AB  - Sn, Sn-Sb, Ti, Zr, Fe, Ce and In oxides are prepared as nanometric powders by the
      hydrolytic route, starting from their ordinary salts or alkoxides, in the
      presence of 5% w/v starch as a non-ionic stabilizer of crystallization nuclei
      versus coalescence and flocculation. The starch can be degraded by a-amylase to
      soluble glucosidic oligomers, which may further be degraded by yeast to CO2 and
      ethanol. The nanoparticle features of prepared oxides result from experimental
      evidence based on X-ray diffractometry, transmission electron microscopy,
      differential thermal analysis/thermogravimetry coupled to mass spectrometry,
      specific surface area and porosity of samples obtained by curing in the 80-600
      degrees C interval.

PMID- 16573106
TI  - Ultra-smooth nanostructured diamond films deposited from He/H2/CH4/N2 microwave
      plasmas.
AB  - Addition of He to a high CH4 content (10.7 vol%) H2/CH4/N2 feedgas mixture for
      microwave plasma chemical vapor deposition produced hard (58-72 GPa), ultra
      smooth nanostructured diamond films on Ti-6AI-4V alloy substrates. Upon increase
      in He content up to 71 vol%, root mean squared (RMS) surface roughness of the
      film decreased to 9-10 nm and average diamond grain size to 5-6 nm. Our studies
      show that increased nanocrystallinity with He addition in plasma is related to
      plasma dilution, enhanced fragmentation of carbon containing species, and
      enhanced formation of CN radical.

PMID- 16573107
TI  - Regenerating optical properties of individual gold nanoparticles in alcoholic
      solvents without any surfactant.
AB  - We compared the optical properties of gold nanoparticles (GNPs) in various
      solvents with those of strawberry-like composite particles (Au/SiO2) consisting
      of a silica core and single attached GNPs. The results show that Au/SiO2 without
      any surfactant could regenerate well optical properties of individual GNPs in
      alcoholic solvents. By the electrophoretic light-scattering measurements, the
      high dispersibility of Au/SiO2 composite particles dispersed in alcoholic
      solvents has been demonstrated. In addition, using Derjaguin-Landau-Verwey
      Overbeek (DLVO) theory, we proposed a possible mechanism to qualitatively account
      for the dispersibility of Au/SiO2 in organic solvents such as alcoholic solvents
      and cyclohexane, which may provide an opportunity to manipulate optical signals
      of single nanoparticle in organic solvents.

PMID- 16573108
TI  - Carbon nanotube-based sensors.
AB  - Sensors continue to make significant impact in everyday life. There has been a
      strong demand for producing highly selective, sensitive, responsive, and cost
      effective sensors. As a result, research emphasis is on developing new sensing
      materials and technologies. Carbon nanotubes (CNTs) have many distinct properties
      that may be exploited to develop next generation of sensors. This manuscript
      reviews the distinct physical, electronic, and mechanical properties of CNTs. The
      main thrust of this review is to highlight the present and future research and
      development work in the area of carbon nanotube sensors for real-world
      applications. The technical challenges associated with CNT-based sensors, which
      remain to be fully addressed, have also been outlined at the end of the
      manuscript. This review aims to act as a reference source for researchers to help
      them in developing new applications of CNT-based sensors.

PMID- 16573109
TI  - Toxicity and biocompatibility of carbon nanoparticles.
AB  - A review is presented of the literature data concerning the effects induced by
      carbon nanoparticles on the biological environment and the importance of these
      effects in human and animal health. The discovery in 1985 of fullerenes, a novel
      carbon allotrope with a polygonal structure made up solely by 60 carbon atoms,
      and in 1991 of carbon nanotubes, thin carbon filaments (1-3 microm in length and
      1-3 nm in diameter) with extraordinary mechanical properties, opened a wide field
      of activity in carbon research. During the last few years, practical applications
      of fullerenes as biological as well as pharmacological agents have been
      investigated. Various fullerene-based compounds were tested for biological
      activity, including antiviral, antioxidant, and chemiotactic activities.
      Nanotubes consist of carbon atoms arranged spirally to form concentric cylinders,
      that are perfect crystals and thinner than graphite whiskers. They are stronger
      than steel but very flexible and lightweight and transfer heat better than any
      other known material. These characteristics make them suitable for various
      potential applications such as super strong cables and tips for scanning probe
      microscopes, as well as biomedical devices for drug delivery, medical diagnostic,
      and therapeutic applications. The effects induced by these nanostructures on rat
      lung tissues, as well as on human skin and human macrophage and keratinocyte
      cells are presented.

PMID- 16573110
TI  - Aerosol phase generation of In-Se nanoparticles.
AB  - Results on the generation and heat treatment of In-Se nanoparticles, made by
      heterogeneous condensation of selenium on indium nanoparticles synthesised via
      the evaporation/condensation route are reported. In-situ aerosol measurements are
      complemented with ex-situ analysis, to provide structural, morphological, and
      compositional information on the In-Se nanoparticles. Our results indicate that
      prior to heat treatment In-Se nanoparticles have a shape in the aerosol phase,
      similar to an asymmetric dumbbell. The bigger particle of the dumbbell structure
      is made up of amorphous Se, while the overall composition of the polycrystalline
      smaller particle is around InSe. The smaller particle has an intrinsic structure,
      and consists of different InSe-compounds, with a decreasing In content towards
      the shell. The shape of the In-Se nanoparticles is different in the aerosol phase
      and on the surface of the samples. The observed variety of particle sizes and
      shapes on the sample surface is shown to be partly due to the agglomeration of
      the aerosol phase binaries (i.e., dumbbells) via coalescence on the surface of
      the sample and wetting of the sample surface by the Se nanoparticles. These
      processes make the bigger particle of the dumbbell structure appear almost
      perfectly hemispherical on the sample surfaces. During heat treatment at lower
      temperatures mainly the evaporative removal of the big Se particle of the
      dumbbell structure will take place. Annealing of the smaller particles starts to
      dominate at temperatures above 240 degrees C and makes the composition of the
      small particles closer to that of the thermodynamically most favoured In2Se3.

PMID- 16573111
TI  - Growth and observation of low-field giant magnetoresistance in La0.7Sr0.3MnO3/ZnO
      superlattice structures.
AB  - We report the growth of a new class of superlattice structure, consisting of
      alternate layers of La0.7Sr0.3MnO3 (LSMO) and ZnO, which exhibits giant
      magnetoresistance at low fields. These superlattices were fabricated using a
      novel pulsed-laser deposition technique with a specially designed target
      assembly. Giant magnetoresistance of > 250% has been observed in these structures
      in current-in-plane configuration on the application of just -400 Gauss of
      magnetic field over the broad temperature range 15-200 K. Observation of giant
      magnetoresistance at such low magnetic fields is a groundbreaking step in the
      field of novel magnetic materials and devices.

PMID- 16573112
TI  - Self-surface passivation of CdX (X = Se, Te) quantum dots.
AB  - A small portion of a reaction mixture including unpurified CdX (X = Se or Te)
      quantum dots (QDs), in which unreacted Cd and Se ions were left together with
      coordinating solvents, was dropped into an organic solvent. The CdX QDs in this
      organic solution showed enhancement of photoluminescence (PL) efficiency, growth
      of particles, and focusing of size distribution for more than 10 h at room
      temperature (RT, -23 degrees C). These effects were attributed to passivation of
      QDs' surface by Cd and X ions present in the solution. No external energy source
      was used for these achievements; therefore, the process is termed as self-surface
      passivation. The self-surface passivation was reproduced using purified CdX QDs
      with additional Cd and X ions in an organic solvent. The self-surface passivation
      method was applied to RT-synthesized CdSe QDs, which is characterized by a broad
      PL spectrum (fwhm - 150 nm) for monodispersed QDs, to modify their emission
      characteristics. On self-surface passivation, the broad PL spectrum was narrowed
      (fwhm - 35 nm) and the QDs were grown. The X-ray diffraction measurements of RT
      synthesized CdSe QDs and that subsequently aged in 1-butanol showed that
      crystallinity of the samples was improved on aging.

PMID- 16573113
TI  - Layer-by-layer nanocoating of lignocellulose fibers for enhanced paper
      properties.
AB  - The systematic modification of the surface charge of lignocellulose fibers was
      performed with a polyelectrolyte layer-by-layer (LbL) nanocoating process to
      produce negatively and positively charged fibers. The fibers were coated with 20
      50 nm thick polymer surface layers which subsequently increased interaction
      between the fibers during paper formation. The modified fibers were added to
      standard fibers at varying proportions to produce paper with corresponding
      variation in properties such as strength and electrical conductivity. Paper
      strength was doubled by manipulating the surface charge and coating thickness of
      the LbL-treated pulp fibers. It is demonstrated that the LbL coating process
      increased the fiber interactions and that these interactions enhanced the paper
      properties. This process, when applied to a simulated sample of recycle grade of
      fibers, produce paper with an increase in tear strength as compared with
      untreated fiber paper. Nanocoating fibers with polythiophene/polyallylamine
      multilayers produced marginally conductive pulp and paper. Paper electrical
      conductivity was proportional to the number of the bilayers deposited.

PMID- 16573114
TI  - Cellulose nanocrystal-filled carboxymethyl cellulose nanocomposites.
AB  - Polymer nanocomposites are one of the important application areas for
      nanotechnology. Naturally derived organic nanophase materials are of special
      interest in the case of polymer nanocomposites. Carboxymethyl cellulose is a
      polyelectrolyte derived from natural materials. It has been extensively studied
      as a hydrogel polymer. Methods to modify the mechanical properties of gels and
      films made from CMC are of interest in our lab and in the commercial marketplace.
      The effect of nano-sized fillers on the properties of CMC-based composites is of
      interest in the development of novel or improved applications for hydrogel
      polymers in general and CMC in particular. This project investigated cellulose
      nanocrystals (CNXLs) as a filler in CMC and compared the effects to
      microcrystalline cellulose (MCC). The composite material was composed of CMC, MCC
      or CNXL, with glycerin as a plasticizer. CNXL and MCC concentrations ranged from
      5% to 30%. Glycerin concentrations were kept constant at 10%. CNXLs improved the
      strength and stiffness of the resulting composite compared to MCC. In addition, a
      simple heat treatment was found to render the nanocomposite water resistant.

PMID- 16573115
TI  - Structural and optical properties of tin oxide branched nanostructures.
AB  - Branched nanostructures of tin oxide (SnO2) have been synthesized by Vapor-Liquid
      Solid (VLS) mechanism using a gold catalyst in the temperature range of 800-850
      degrees C under an ambient gas flow of 200 sccm. The microstructural and the
      optical properties of the as prepared products have been studied by X-ray
      diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), micro-Raman, and photoluminescence (PL) studies. SnO2 branches
      with a rutile phase are found to have a preferential orientation along (101).
      Typical lengths of these branches are found to be approximately 3-5 microm and
      diameters in the range of 50-100 nm. Selected area electron diffraction (SAED)
      pattern shows that the SnO2 branches have a tetragonal cross section with [101]
      crystal direction. A Raman line at 631 cm(-1) (Sn-O bond) is obtained in the
      micro Raman spectra. Low temperature PL spectrum shows a strong green emission
      band near 506 nm.

PMID- 16573116
TI  - Effect of sodium dodecylsulfate and dodecyltrimethyl ammonium bromide on the
      morphologies of gold nanoparticles in the presence of poly(amidoamine)
      dendrimers.
AB  - The synthesis of gold nanoparticles has been carried out in aqueous phase in the
      presence of both ionic surfactants (i.e., sodium dodecylsulfate (SDS) and
      dodecyltrimethylammonium bromide (DTAB)) and poly(amidoamine) dendrimers (PAMAM).
      It has been observed that the fluoroderivative of 2G PAMAM (2D) acts as reducing
      agent in reducing Au(lll) to Au(0) leading to the formation of fine gold
      nanoparticles. This process has been further evaluated in the presence of fixed
      amounts of both SDS and DTAB in their respective pre and post micellar
      concentration regions. The presence of SDS leads to the appearance of clear
      ordered morphologies such as triangular, hexagonal, spherical, and rod shaped,
      while the presence of DTAB does not show this effect. The formation of
      nanoparticles in triangular morphologies is more significant in the premicellar
      concentration range of SDS whereas hexagonal morphologies in the post micellar
      concentration range. On the contrary, increase in the DTAB concentration from pre
      to post micellar range only reduces the size of gold nanoparticles without the
      appearance of any ordered morphology. The formation of ordered gold nanoparticles
      in the presence of SDS has been further attributed to the significant SDS
      dendrimer interactions and an appropriate mechanism has been proposed to justify
      the results.

PMID- 16573118
TI  - Focused ion beam nanofabrication: a comparison with conventional processing
      techniques.
AB  - Focused ion beam and dual platform systems are versatile tools for
      nanoengineering and nanoscience applications. These systems complement
      conventional processing methods and can be used to prototype and modify a diverse
      range of nano-devices and sensors. This article discusses FIB nanofabrication and
      compares it with other fabrication techniques such as electron beam lithography
      and reactive ion etching. Aspects such as the minimum feature size and side wall
      profiles are discussed and compared. In addition, the limitations and detrimental
      effects of FIB processes are discussed.

PMID- 16573117
TI  - High energy density processing of a free form Nickel-alumina nanocomposite.
AB  - The development of a free form bulk Nickel reinforced Alumina matrix nano
      composites using Air Plasma Spray and laser processing has been presented. The
      process consumes less time and requires further minimal machining and therefore
      is cost effective. The relative differences in using APS over laser processing in
      development of bulk metal-ceramic nanocomposites have been discussed. The process
      intricacies involved during processing such as material specific mandrel
      selection, plasma-particle interaction are highlighted. Electroless coating has
      been used to uniformly disperse Nickel in alumina matrix as a source material.
      The electroless Ni coated alumina particles are subjected to both laser
      processing and Air Plasma Spraying with optimized parameters. Consolidation by
      laser processing could not be achieved as the laser beam was reflective to
      Nickel. On the other hand, APS Ni-alumina nanocomposite with a cylindrical shape
      of 1.2" OD x 1" ID x 1.5" length has been fabricated with minimum or no surface
      defects. HRTEM pictures revealed the nanostructure retention thereby
      corroborating the fact that bulk nanostructures can be made using Air Plasma
      Spray. XRD analysis confirmed the phase transformation from alpha alumina to
      gamma alumina and oxidation of Ni to NiO. Subsequent reduction of NiO to metallic
      nickel using hydrogen atmosphere has also been demonstrated. Mechanical
      properties such as, hardness (1025 HV) and fracture toughness (5 MPa m1/2) for
      the nanocomposite are presented herein.

PMID- 16573119
TI  - A simple and rapid method of making 2D and 3D arrays of gold nanoparticles.
AB  - Monodispersive gold nanoparticles can be synthesized by a dropwise addition of a
      reducing agent microemulsion to a gold ion microemulsion followed by immediate
      stabilization with 1-decanethiol. No size-selective precipitations or digestive
      ripening procedures are necessary. There is no need for metal functionalization
      of the surfactant AOT. Gold nanoparticles with an average size of 3.8 nm and a
      relative size dispersion of 5.4% were observed using n-heptane as a solvent. It
      seems possible to adjust the nanoparticle size by small changes in the carbon
      chain length of the solvent. Self-assembled 2D and 3D arrays of gold
      nanoparticles with adjustable sizes have been obtained on carbon-coated copper
      grids and on a silicon wafer. The arrays have good crystallinity as evidenced by
      the external morphology and transmission electron diffraction results. The size
      of the gold nanoparticle 3D arrays depends on the immersion time and can be
      greater than 15 microm. This approach could be used to synthesize other noble
      metal nanoparticle arrays that may lead to new materials for electronic and
      photonic applications.

PMID- 16573120
TI  - Encoding information using molecular vibronics.
AB  - Signals carrying information are encoded in molecular vibrational waves
      (vibronics) rather than in electric currents as widely done in microelectronics.
      We demonstrate theoretically that signals can be transmitted along a long
      polypeptide molecule; the signal is modulated in a terahertz carrier
      corresponding to a frequency of an intrinsic vibrational mode of the backbone of
      the polypeptide, via amplitude and frequency modulations. The modulated carrier
      is coupled as a vibrational wave to the polypeptide at one end of the molecule
      and propagates for more than 168 angstroms towards the other end. Digital signal
      processing techniques are used to recover the modulated signals.

PMID- 16573121
TI  - Thermal diffusivity of nanofluids containing Au/Pd bimetallic nanoparticles of
      different compositions.
AB  - Colloidal suspensions of bimetallic Au/Pd nanoparticles were prepared by
      simultaneous reduction of the metal ions from their corresponding chloride salts
      with polymer (PVP) stabilizer. Thermal properties of water containing bimetallic
      nanoparticles with different nominal compositions (Au/Pd = 12/1, 5/1, 1/1, 1/5)
      were measured using the mode mismatched dual-beam thermal lens technique to
      determine the effect of particle composition on the thermal diffusivity of the
      nanofluids. The characteristic time constant of the transient thermal lens was
      estimated by fitting the experimental data to the theoretical expression for
      transient thermal lens. The thermal diffusivity of the nanofluids (water,
      containing Au/Pd bimetallic nanoparticles) is seen to be strongly dependent on
      the composition of the particles. The maximum diffusivity was achieved for the
      nanoparticles with highest Au/Pd molar ratio. A possible mechanism for such high
      thermal diffusivity of the nanofluids with bimetallic particles is given. UV-Vis
      spectroscopy, TEM and high-resolution electron microscopy (HREM) techniques were
      used to characterize the Au/Pd bimetallic nanoparticles.

PMID- 16573122
TI  - Synthesis of noble metal/carbon nanotube composites in supercritical methanol.
AB  - A simple and efficient route has been employed to deposit noble metal
      nanoparticles (Pt, Ru, Pt-Ru, Rh, Ru-Sn) onto carbon nanotubes (CNTs) in
      supercritical methanol solution. In this method, the inorganic metallic salts
      acted as metal precursors, and methanol as solvent as well as reductant for the
      precursors. The as-prepared nanocomposites were structurally and morphologically
      characterized by X-ray diffraction spectroscopy, transmission electron microscopy
      (TEM), scanning electron microscopy, and X-ray photoelectron spectroscopy
      analyses. It was demonstrated that the CNTs were decorated by crystalline metal
      nanoparticles with uniform sizes and a narrow particle size distribution. The
      size and loading content of the nanoparticles on CNTs could be tuned by
      manipulating reaction parameters. Furthermore, the formation mechanism of the
      composites was also discussed.

PMID- 16573123
TI  - Single crystalline nature of para-sexiphenyl crystallites grown on KCl(100).
AB  - This work focuses on studies of the single crystal nature of para-sexiphenyl
      structures grown on freshly cleaved KCl(100) surfaces. Two different kinds of
      morphologies, namely terrace like structures and needle like structures, are
      found by atomic force microscopy as well as by electron microscopy. Regardless of
      the morphology the individual crystallites show highly regular shapes. The
      crystalline alignment and the degree of order of the crystallites on the surface
      are determined by X-ray diffraction. Several epitaxial alignments of para
      sexiphenyl on KCl(100) are observed and all of them are perfectly aligned on the
      surface. The rocking curve widths of the organic crystallites do not exceed 800"
      which is approximately only the four fold of the substrates' ones. The single
      crystalline nature of para-sexiphenyl crystallites is proven by transmission
      electron microscopy, diffraction patterns, dark field imaging and high resolution
      techniques. Single crystalline terraced mounds reach diameters of several microns
      and heights of 50 nm. Single crystal needles show heights and breadths of more
      than 100 nm and lengths of several microns.

PMID- 16573124
TI  - Preparation of high purity ZnO nanobelts by thermal evaporation of ZnS.
AB  - High purity one-dimensional ZnO nanobelts were synthesized by thermally
      evaporating commercial ZnS powders in a hydrogen-oxygen mixture gas at 1050
      degrees C. It was found that these ZnO nanobelts had a single crystal hexagonal
      wurtzite structure growing along the [0001] direction. They had a rectangle
      shaped cross-section with typical widths of 20 to 100 nanometers and lengths of
      up to hundreds of micrometers with lattice constants of a = 0.325 nm and c =
      0.520 nm. The self-catalytic hydrogen-oxygen assisted growth of ZnO nanobelt is
      discussed. The photoluminescence (PL) characterization of the ZnO nanobelts shows
      strong near-band UV emission (about 383 nm) and one broad peak at 501 nm, which
      indicates that the ZnO nanobelts have good potential application in
      optoelectronic devices.

PMID- 16573125
TI  - Preparation of very reactive thiol-protected gold nanoparticles: revisiting the
      Brust-Schiffrin method.
AB  - The preparation and properties of tert-dodecanethiol protected gold nanoparticles
      amenable to very rapid surface functionalization by associative mechanism is
      described. The new material can be easily prepared by controlling the reaction
      time, because only a limited but enough number of tert-dodecanethiol to stabilize
      the gold clusters is bond to the surface until about an hour. Accordingly, it can
      be isolated as a solid and handled much like the highly stabilized Brust
      Schiffrin analogues, but reacted very rapidly with any molecular species
      containing one or multiple functional groups such as thiol, disulfide, pyridine,
      etc. These characteristics are ideal for the preparation of a variety of new
      organic-inorganic hybrid nanomaterials by coordinative self-assembly. This
      possibility was illustrated using meso-tetra(4-pyridyl)porphyrin, which promptly
      bonded to the reactive protected gold nanoparticles generating a solid that can
      be grown as thin films with layer-by-layer control on a suitably modified
      surface.

PMID- 16573126
TI  - Electrochemical hydrogen storage in single-walled carbon nanotube paper.
AB  - Single-walled carbon nanotube (SWNT) papers were successfully prepared by
      dispersing SWNTs in Triton X-100 solution, then filtered by PVDF membrane (0.22
      microm pore size). The electrochemical behavior and the reversible hydrogen
      storage capacity of single-walled carbon nanotube (SWNT) papers have been
      investigated in alkaline electrolytic solutions (6 N KOH) by cyclic voltammetry,
      linear micropolarization, and constant current charge/discharge measurements. The
      effect of thickness and the addition of carbon black on hydrogen
      adsorption/desorption were also investigated. It was found that the
      electrochemical charge-discharge mechanism occurring in SWNT paper electrodes is
      somewhere between that of carbon nanotubes (physical process) and that of metal
      hydride electrodes (chemical process), and consists of a charge-transfer reaction
      (Reduction/Oxidation) and a diffusion step (Diffusion).

PMID- 16573128
TI  - Preparation of vermiculite nanoparticles using thermal hydrogen peroxide
      treatment.
AB  - Powdered natural Mg-vermiculite (Letovice, Czech Republic), with the formula
      (Mg0.35K0.02Ca0.01) (Mg2.39Fe0.51(3+)Fe0.02(2+)Al0.08) (Si2.64Al1.33Ti0.03)
      O10(OH)2 x 4.97H2O and particle size < 5 microm, was used for the investigation
      of exfoliation after hydrogen peroxide and/or microwave treatment (600 W). A
      sample heated in the microwave oven for 40 min exhibits a 11% mass loss and
      reduction of the 001 peak intensity in the X-ray diffraction pattern. The basal
      001 peak intensity of untreated Mg-vermiculite sample (/001 = 100%) drops to 35%
      in the microwave treated sample. Only the sample treated for 5 h at 80 degrees C
      fully rehydrated after 120 min at room temperature. A more pronounced reduction
      of the 001 peak intensity (to 8%) was observed after hydrogen peroxide treatment
      of the sample at 25 degrees C. The combination of a five-hour hydrogen peroxide
      treatment at 80 degrees C and subsequent microwave heating leads to an effective
      extinction of the 001 diffraction in the XRD pattern. The 001 diffraction profile
      becomes very diffuse with peak intensity less than 1%. The degree of reduction of
      the 001 diffraction intensity also depends on the time and temperature of
      hydrogen peroxide treatment and on the peroxide concentration. An even more
      pronounced reduction of the peak intensity is caused by exfoliation of particles
      to nano-domains coupled with a randomization of the c-axes.

PMID- 16573127
TI  - Nanorods of tellurium: synthesis and self-assembly.
AB  - A simple solution phase approach is described to prepare tellurium nanorods which
      undergo morphological modifications to yield different microstructures under
      varied experimental conditions. The morphology of the prepared products is
      drastically altered in presence of a few oxidizing agents such as sodium
      oxychloride (NaOCl), hydrogen peroxide (H2O2) etc. The effects of poly (sodium 4
      styrene sulphonate) (PSS) and Isooctyl phenoxy poly oxyethanol (TritonX-100) on
      the size and shape of the products in presence of air/NaOCl have also been
      monitored.

PMID- 16573129
TI  - Self-organized CdSSe quantum dots thin films.
AB  - Self-organized and strained CdSSe quantum dot (Q-dot) thin films have been grown
      on ITO-coated glass substrates by novel wet chemical route. The Q-dots are (002)
      oriented faceted pyramids with average particle size of 7.5 nm. The X-ray
      diffraction results reveal the formation of a solid solution of CdSSe. Atomic
      force microscopy is used to investigate the morphology of the nanocrystalline
      thin films. The energy dispersive X-ray analysis spectrum confirms the presence
      of Cd, S, and Se in the films. Optical absorption and photoluminescence spectra
      show the blue shift for quantum dot thin films.

PMID- 16573130
TI  - Surfactant-assisted synthesis and characterization of SrCrO4 nanostructures.
AB  - A simple and efficient microemulsion-based technique, which used the new Tx
      100/cyclohexanol/ H2O system, was developed to synthesize SrCrO4 nanowire based
      nanostructures, including nanowire bundles and flower-like structures at
      different temperature. X-ray powder diffraction (XRD), field emission scanning
      electron microscope (FE-SEM), transmission electron microscopy (TEM) and high
      resolution TEM (HRTEM) were used to characterize the products. Studies found that
      the reaction temperatures and the reaction systems have great influences on the
      final products. Optical properties studies by UV-Vis spectra and
      photoluminescence (PL) spectra confirmed that the as-obtained nanowires showed
      distinct optical activity under UV and visible light irradiation.

PMID- 16573131
TI  - Synthesis and characterization of Fe/Nd2O3 core-shell nanoparticles by hydrogen
      plasma-metal reaction.
AB  - Fe/Nd2O3 core-shell nanoparticles (CSNs) with a mean diameter of 35 nm were
      produced successfully by using hydrogen plasma-metal reaction (HPMR) method. This
      core-shell structure was confirmed by high resolution transmission electron
      microscopy (HRTEM), energy dispersion X-ray spectroscopy (EDS), X-ray
      photoelectron spectral (XPS), and induction-coupled plasma (ICP) spectroscopy.
      The magnetic properties were measured by vibrating sample magnetometer (VSM). It
      was found that the mole ratio of Nd to Fe on the nanoparticle surface is 1.2:1,
      about 7 times of that of the whole nanoparticle. The saturation magnetization Ms
      and remanence Mr of Fe/Nd2O3 nanoparticles decrease prominently from Fe
      nanoparticles, whereas the coercivity Hc drops only less than 5% of Fe
      nanoparticle. These CSNs have potential applications in magnetic and catalytic
      fields.

PMID- 16573132
TI  - Experimental study of interaction of laser radiation with silver nanoparticles in
      SiO2 matrix.
AB  - Thin films of silica containing silver nanoparticles were deposited by magnetron
      co-sputtering followed by thermal annealing in air or Ar+2% H2. Laser
      fragmentation of the particles was carried out at two different wavelengths. The
      films were characterized by UV-VIS absorption spectroscopy and plasmon resonance
      numerical modeling based on the Mie theory, together with Rutherford
      backscattering elemental analysis, X-ray photoelectron spectroscopy chemical
      characterization, combined with statistical analysis of the transmission electron
      microscopy micrographs, and surface topography study by atomic force microscopy.
      It is demonstrated that the fragmentation is a result of a thermal process and
      its mechanism does not depend on the laser wavelength as long as the laser light
      is absorbed by the silver particles. Laser treatment with moderate fluences does
      not alter the precipitated metal content while fragmenting the particles. TEM
      study indicates that laser assisted silver particle modification can serve as a
      method for narrowing the particle size distribution.

PMID- 16573133
TI  - Synthesis of nanocrystalline La(Ca)CrO3 through a novel gel combustion process
      and its characterization.
AB  - La(Ca)CrO3 (LCC) powders have been prepared through a novel gel combustion route
      using metal nitrates as oxidizers and ethylene diamine tetraacetic acid (EDTA) as
      a fuel. The process involves the combustion of a viscous gel obtained through
      mixed metal nitrate-EDTA solution. The effect of amount of EDTA used in the
      process on the nature of combustion reaction, phase formation, and densification
      has been studied. It was found that use of the fuel-rich precursor facile in
      controlling the reaction, which in turn helps in the scale up of the batch size.
      The calcination of the fuel-rich gel precursor at 650 degrees C resulted in the
      well-crystalline LCC along with a small amount of calcium chromate as a secondary
      phase. The HRSEM studies on the powder showed agglomerated nanoparticles. The
      average agglomerate size was found to be 0.54 microm. The cold pressing and
      sintering of the calcined powder at 1250 degrees C resulted in the mono-phasic
      La0.70Ca0.30CrO3 with 94% of its theoretical density. The sintered sample
      exhibited conductivity of 51 S/cm at 1000 degrees C. The average linear thermal
      expansion coefficient was found to be 10.3 x 10(-6) degrees C(-1).

PMID- 16573134
TI  - Effect of niobium on the structure and photoactivity of anatase (TiO2)
      nanoparticles.
AB  - Anatase-type TiO2 nanoparticles doped with 0-30 mol% niobium were directly formed
      from precursor solutions of TiOSO4 and NbCl5 under mild hydrothermal conditions
      at 120-180 degrees C for 5 h using the hydrolysis of urea. When the niobium
      content increased from 0 to 30 mol%, the crystallite size of anatase increased
      from 8.5 to 19 nm. The band gap of anatase was slightly decreased by making solid
      solutions with niobium. Their photocatalytic activity and adsorptivity were
      evaluated separately by the measurement of the concentration of methylene blue
      (MB) remained in the solution after maintained in the dark or under UV-light
      irradiation. To form anatase-type solid solutions by doping 5-15 mol% niobium
      into TiO2 was effective for improvement of the photoactivity of TiO2. The
      photocatalytic activity (the photooxidation rate) and the adsorption amount of MB
      for the sample containing 15 mol% niobium became more than approximately nine
      times and six times as much as those of the hydrothermal anatase-type pure TiO2,
      respectively.

PMID- 16573135
TI  - Morphology and size dependent optical properties of CdS nanostructures.
AB  - CdS nanoparticles with different sizes ranging from 2.5 nm to 300 nm and nanorods
      with aspect ratio -32 were synthesized by simple solvothermal process with a view
      to explore the effect of size and shape on the optical properties of these
      nanoforms. Solvent, temperature and the Cd source played important role in
      determining the morphologies and sizes of the nanocrystals. Comparative study of
      the optical properties of these nanoforms showed systematic changes in the
      optical absorption spectra with the reduction in particle size. Nanorods showed
      bulk like properties. Photoluminescence and Raman studies were carried out to
      explore the size and morphology dependent optical properties of the CdS
      nanoforms.

PMID- 16573136
TI  - In-situ preparation of binary-phase silver nanoparticles at a high Ag+
      concentration.
AB  - Stable and monodisperse silver nanoparticles (NPs) have been synthesized using
      high metal salt concentration (up to 0.735 M) through a simple but novel
      technique. It is based on one-step procedure that uses glycerol for reducing Ag+
      in the presence of o-phenylenediamine (o-PDA) resulting the nanoparticles are in
      two forms (one water-soluble, the other a precipitated). The water-soluble phase
      contains NPs that have a bimodal size distribution (2-3 and 5-6 nm); the other
      comprises precipitated NPs, having a unimodal size distribution (2-3 nm). The
      water-soluble NPs are covalently bonded to the aromatic amine molecules to form
      isolated units, while the precipitated nanoparticles are embedded in the networks
      formed by cross-linking between COOH groups of hydroxypyruvic acid (oxidized form
      of glycerol) and NH2 groups of o-PDA molecules. We used transmission electron
      microscopy (TEM), UV-Vis spectroscopy, X-ray diffraction (XRD), Fourier transform
      infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS) to
      characterize the silver products obtained.

PMID- 16573137
TI  - Conductive super-hydrophobic surfaces of polyaniline modified porous anodic
      alumina membranes.
AB  - A conductive polymer polyaniline (PANI) was employed to achieve surfaces of both
      super-hydrophobic and conductive on NaOH etched porous anodic alumina (PAA)
      membranes. The surfaces exhibit micro- and nanostructures. In the PANI modified
      PAA membrane, PANI is mainly emeraldine. After the membrane was immersed in HCl,
      the content of the protonated nitrogen increased, which increased the
      conductivity.

PMID- 16573138
TI  - Controlled synthesis and field emission properties of ZnO nanostructures with
      different morphologies.
AB  - By simply controlling atmosphere, rods, tetraleg-rods, and arrays of ZnO
      nanostructures have been fabricated respectively through pure zinc powder
      evaporation without catalyst at temperature of 650 - 700 degrees C.
      Investigations through HRTEM and XRD showed that the growth of the synthesized
      ZnO nanostructures was controlled by vapor-solid mechanism. Field emission
      measurements revealed that all of the structures, owing to their very low turn-on
      voltage, sufficient emission current and proper linearity of 1/V - Ln(l/V2), are
      likely to be potential candidates as a field emitter. The results also indicated
      that field emission properties are relative to morphology and size of the tips of
      ZnO nanostructures, and the nanorods with sharp tips possess the first-class FE
      property.

PMID- 16573139
TI  - Synthesis of silica nanowires by active oxidation of silicon substrates.
AB  - Amorphous silica nanowires have been produced by thermal annealing of Si/SiO2/Ni
      substrate structures at 900 degrees C under an atmosphere of hexamethyldisilazane
      (HMDS) and hydrogen (H2). The wires have diameter ranging from 35 to 55 nm, which
      are controlled by the Ni particle size. It is demonstrated that the growth occurs
      through vapor-liquid-solid mechanisms, and it is proposed that the vapor source
      is volatile SiO generated from the etching of the Si substrate through active
      oxidation reactions. The role of the HMDS-H2 atmosphere in promoting such
      reactions is discussed.

PMID- 16573140
TI  - Inlaying nanoscale surface recess patterns with nanoscale objects.
AB  - A simple and versatile approach to constructing patterns on a solid surface using
      nanoscale objects is demonstrated. The approach is essentially an inlaying
      process, in which recess patterns fabricated on a surface are selectively filled
      with nanoscale objects. The objects are anchored firmly on the surface due to the
      spatial confinement provided by the recess structures. Protein molecules and
      inorganic nanoparticles are used in this demonstration. Cyclic voltammetry is
      used to detect electron transfer signals from patterns of protein molecules. The
      approach suggests a potentially fast, high-throughput and versatile technique for
      constructing architectural structures on a solid surface using nanoscale objects.

PMID- 16573141
TI  - ZnO nanorods on in-situ synthesized ZnSe grains.
AB  - The ZnO nanorods grown on in-situ synthesized ZnSe grains through the chemical
      vapour deposition method are reported here for the first time. With a suitable
      growth condition, single crystal ZnO nanorods grow on the well-defined bounded
      facets of the random shape ZnSe grains using Zn and Se powders without any metal
      catalyst. The growth direction of ZnSe nanorods on a facet of a ZnSe grain is
      quite uniform. The synthesis mechanism of the ZnO nanorods on the ZnSe grains is
      proposed. The effects of the Se powder usage on the ZnO-ZnSe products and the
      photoluminescence of the products are investigated.

PMID- 16573142
TI  - Generation of CdS nano-necklaces and NiS nanotubes templated by sugar-appended
      hydrogel.
AB  - A new hydrogel based on glucose-appended Schiff base derivative has been employed
      as the template to synthesize CdS and NiS nanostructures with different
      morphologies. The FT-IR and UV-vis results revealed that H-bonding and pi-pi
      interaction played important roles in the formation of original hydrogel fibers.
      The study of mineralization mechanism suggested that the inorganic ions were
      firstly adsorbed at the surface of the hydrogel fibers due to the hydrophilic
      affinity with the hydrophilic glucose groups. With the penetration of H2S gas,
      the preformed CdS or NiS nanoparticles on the surface of the fibers acted as the
      growing points for the continuous growth. And the different adsorption abilities
      of the metal ions at the hydrogel fibers resulted in the formation of CdS nano
      necklaces and NiS nanotubes.

PMID- 16573143
TI  - Room temperature formation of ammonia by oxidizing hydrogenated cerium
      nanoparticles in the air.
AB  - Ammonia formation was observed when hydrogenated cerium nanoparticles prepared by
      hydrogen plasma-metal reaction (HPMR) were exposed to the air at room
      temperature. This novel phenomenon represents a successful example of room
      temperature cleavage of dinitrogen and may find application in low temperature
      synthesis of ammonia under thermodynamically favorable conditions. A possible
      mechanism is also proposed. We suggest that the oxidation of cerium hydride
      offers chemical force to drive the hydrogen atoms out of the lattice. The
      monoatomic H released to the surface is highly active and readily reacts with N2
      to yield ammonia. Some surface processes, which we know little about at the
      moment, are likely to be involved so as to lower the energy barrier of nitrogen
      dissociation. Further investigation is required to elucidate the detailed
      mechanism.

PMID- 16573144
TI  - Controlled synthesis of manganese oxohydroxide (MnOOH) and Mn3O4 nanorods using
      novel reverse micelles.
AB  - Novel reverse micelles of high CTAB concentration were successfully developed to
      synthesize MnOOH (manganese oxyhydroxide) nanorods with uniform diameters of
      about 10 nm and up to 200 nm in length under mild solution conditions and Mn3O4
      nanorods with the same morphology could be obtained by calcining the precursors
      at 450 degrees C. The morphology and microstructure of the nanorods were
      investigated by transmission electron microscopy (TEM and HRTEM), XRD and TGA.
      The results showed that the concentration of CTAB was a key factor for the
      formation of MnOOH nanorods and only above 0.2 M the nanorods could be obtained.
      Moreover, the length of nanorods increased with the increase of CTAB
      concentration, while the diameter of nanorods retained steadily. In this way, the
      length of nanorods could be easily controlled from tens nanometers to hundreds
      nanometers by increasing the CTAB concentration from 0.35 M to 1.25 M. In
      addition, in our experiment the products were almost entirely rod-like shape,
      which indicated this method should be suitable for mass-producing.

PMID- 16573145
TI  - Synthesis and characterization of ultrafine poly(vinylalcohol phosphate) coated
      magnetite nanoparticles.
AB  - Nanosized magnetite (Fe3O4) particles showing superparamagnetism at room
      temperature have been prepared by controlled coprecipitation of Fe2+ and Fe3+ in
      presence of highly hydrophilic poly(vinylalcohol phosphate)(PVAP). The impact of
      polymer concentration on particle size, size distribution, colloidal stability,
      and magnetic property has been extensively studied. The aqueous suspension of
      magnetite, prepared using 1% PVAP solution is stable for four weeks at pH 5-8. X
      ray diffractograms show the formation of nanocrystalline inverse spinel phase
      magnetite. Transmission Electron Microscopy confirmed well dispersed cubic
      magnetite particles of size of about 5.8 nm. Dynamic Light Scattering measurement
      shows narrow distribution of hydrodynamic size of particle aggregates. Infrared
      spectra of samples show strong Fe--O--P bond on the oxide surface. UV-visible
      studies show aqueous dispersion of magnetite formed by using 1% PVAP solution is
      stable at least for four weeks without any detoriation of particle size.
      Magnetization measurements at room temperature show superparamagnetic nature of
      polymer coated magnetite nanoparticles.

PMID- 16573146
TI  - Synthesis and luminescence properties of lanthanide (III)-doped YF3
      nanoparticles.
AB  - Synthesis process and luminescence properties of trivalent lanthanide ions (Ln3+)
      doped YF3 nanoparticles have been investigated. To synthesis Ln(3+)-doped YF3
      nanoparticles, the mixture of (YCl3 x nH2O + LnCl3 x nH2O), and NH4F was
      hydrothermal treated at 180 degrees C in a Teflon-liner auto-clave or heated at
      higher temperatures (400 degrees C - 600 degrees C) in a stove. The XRD patterns
      showed that the Ln(3+)-doped orthorhombic YF3 nanoparticles with no second phase
      have been prepared. The solid solution Y(1-x)Eu(x)F3 (x = 0 - 0.4) nanoparticles
      have been synthesized. The luminescence concentration quenching resulted from
      resonance energy transfer between neighboring Eu3+ ions occurred at higher Eu3+
      concentrations (30 mol%). The upconversion luminescence of Er(3+)-Yb3+ codoped
      YF3 nanoparticles under 980 nm excitation has also been observed. With increase
      of heated temperature, the size of the Er(3+)-Yb3+ codoped YF3 nanoparticles
      increased gradually, and upconversion luminescence intensity increased
      significantly.

PMID- 16573147
TI  - Adhesion and structure properties of protein nanomaterials containing hydrophobic
      and charged amino acids.
AB  - Protein polymers are being used or considered for biobased adhesives and coating
      materials. Most adhesives derived from macro protein molecules work through
      receptors or cross-links to bring about adhesion. The adhesion mechanism of
      protein polymers would lead to better understanding of adhesives and the
      discovery of new practical properties of protein polymers at both nano- and macro
      scales. The objective of this research work was to study adhesion properties of
      protein polymers at nanoscale (a peptide adhesive with nanometer-scale units that
      range in size of several nanometers, defined as protein nanomaterial). Seven
      protein nanomaterial samples with different degrees of adhesive strength were
      designed and synthesized using solid phase chemistries. All protein nanomaterials
      contain a common hydrophobic core flanked by charged amino acid sequences. The
      adhesion properties of the protein nanomaterials were investigated at different
      pH values and curing temperatures. The protein nanomaterials self aggregate and
      interact with the wood surface. The protein nanomaterial KKK-FLIVIGSII-KKK
      identified in this study had high adhesive strength toward wood. It had the
      highest shear strength at pH 12, with an amino acid sequence that was very
      hydrophobic and uncharged. This protein nanomaterial underwent structural
      analyses using circular dichroism, laser-Fourier transform infrared, and laser
      desorption mass spectrometry. At pH 12 this peptide adopted a pH-induced beta
      like conformation. Adhesive strength reflects contributions of both hydrogen
      bonding and van der Waals interactions. Ionic and covalent bonds do not appear to
      be significant factors for adhesion in this study.

PMID- 16573148
TI  - A microwave route for the synthesis of nanoflakes and dendrites-type beta-ln2S3
      and their characterization.
AB  - In this article, a simple microwave route was applied for the synthesis of
      nanoflakes and dendrite-type beta-indium sulfide (In2S3) in high yield (> 97%),
      using a homogeneous mixture of indium(lll)chloride and thiourea in an ethylene
      glycol (EG)/polyethylene glycol (PEG400) solvent. The reaction was conducted in a
      simple domestic microwave oven (DMO). Powder X-ray diffraction (XRD), low
      resolution and high resolution transmission electron microscopy (LRTEM and
      HRTEM), selected area electron diffraction (SAED), and energy dispersive X-ray
      spectroscopy (EDS), were applied to investigate the crystallinity, structure,
      morphology, and composition of the In2S3 nano-materials. Both the as-synthesized
      and calcined In2S3 products were a body-centered tetragonal (bct) phase, observed
      by XRD and HRTEM. The length and width of the resulting nanoflakes were in the
      range of 70-600 nm and 4-10 nm, respectively. The optical band gap of the powder
      was determined by diffuse reflectance spectroscopy (DRS) and was found to be 2.44
      eV. The electronic properties of the products were studied by measuring the
      optical absorption spectra using photoacoustic spectroscopy. The band gap
      calculated by this method was found to be 2.52 eV. A possible mechanism for the
      formation of nanoflakes/dendrites-type In2S3 was also discussed.

PMID- 16573149
TI  - Room temperature solvent-free synthesis of monodisperse magnetite nanocrystals.
AB  - We have successfully demonstrated a facile, solvent-free synthesis of highly
      crystalline and monodisperse Fe3O4 nanocrystallites at ambient temperature
      avoiding any heating. Solid state reaction of inorganic Fe(ll) and Fe(ll) salts
      with NaOH was found to produce highly crystalline Fe3O4 nanoparticles. The
      reaction, if carried out in the presence of surfactant such as oleic acid
      oleylamine adduct, generated monodisperse Fe3O4 nanocrystals extractable directly
      from the reaction mixture. The extracted nanoparticles were capable of forming
      self-assembled, two-dimensional and uniform periodic array. The new process
      utilizes inexpensive and nontoxic starting materials, and does not require a use
      of high boiling point and toxic solvents, thus is amenable to an environmentally
      desirable, large-scale synthesis of nanocrystals.

PMID- 16573150
TI  - Synthesis and growth mechanism of selenium nanowire bundles via a polymer
      controlled chemical route.
AB  - This article describes a polymer-controlled chemical method for synthesis of
      trigonal selenium (t-Se) nanowire bundles in the presence of poly(vinyl alcohol)
      (PVA) at 100 degrees C. Electron microscope images show that Se nanowires have
      diameters of 30-50 nm and lengths of up to a few tens of micrometers. TEM images
      display the direct evidence for the growth process of single-crystalline Se
      nanowire bundles, which suggested that Se nanowire bundles were directly
      converted from the initial amorphous Se micro-particles in the presence of PVA.
      UV-Vis absorbance of t-Se nanowire bundles revealed that the bandgap and
      absorbance peaks displayed larger blue shifts relative to those of bulk t-Se.

PMID- 16573151
TI  - Mn-doped zinc aluminate nanoparticles: hydrothermal synthesis, characterization,
      and photoluminescence properties.
AB  - A two-step synthesis method was developed to fabricate Mn-doped zinc aluminate
      (ZnAl2O4) nanoparticles, including the first step of ageing, and the second step
      of crystallization. The effects of preparation conditions, such as ageing
      temperature, crystallization time, and the pH on the Mn-doped ZnAl2O4
      nanoparticles were systematically investigated. The photoluminescence (PL)
      properties of green phosphor Mn-doped ZnAl2O4 nanoparticles were also discussed.
      Compared with the bulk sample, the PL spectrum of Mn-doped ZnAl2O4 nanoparticles
      has distinct blue shift. This procedure provides a facile way for the synthesis
      of well-crystallized ZnAl2O4:Mn at low temperature.

PMID- 16573152
TI  - Carbon nanotubes for immunomagnetic separation of Escherichia coli O157: H7.
AB  - Bovine serum albumin-functionalized multiple-walled carbon nanotubes with
      encapsulated ferromagnetic elements were conjugated with pathogen-specific
      antibody, and the conjugate was evaluated for immunomagnetic separation of
      Escherichia coli O157:H7 in pure and mixed (with Salmonella Typhimurium)
      cultures.

PMID- 16573153
TI  - Influence of cation-adsorption and sonochemical approaches on the preparation of
      gold catalyst.
AB  - Nanosize mesoporous ZrO2 support was synthesized via a solid-state reaction
      route. A new preparation method involving cation-adsorption and sono-chemical
      procedure was developed for mesoporous ZrO2 supported nano-gold catalyst.

PMID- 16573154
TI  - [Breast reconstruction with a combined skin flap of DIEP and TRAM].
AB  - OBJECTIVE: To evaluate breast reconstruction with a combined skin flap of the
      deep inferior epigastric perforator (DIEP) and the transverse rectus abdominis
      musculocutaneous (TRAM). METHODS: The DIEP and TRAM united flap was elevated with
      the vessel pedicle of the deep inferior epigastric perforator on the affected
      side and the rectus abdominis muscle pedicle on the intact side. The
      reconstructive breast was shaped after the deep inferior epigastric vessels were
      anastomosed to the internal mammary vessels or the thoracodorsal vessels
      ipsilaterally. RESULTS: We have used the DIEP and TRAM united flaps for breast
      reconstruction in 17 cases. All of the flaps survived, and the reconstructed
      breasts were well-shaped with the follow-up of 6-18 months. CONCLUSIONS: The DIEP
      and TRAM united flap possesses of advantages such as rich blood supply, abundant
      tissue volume and easy shaping. It is especially applicable to the cases who have
      large chest defect and need large volume tissue.

PMID- 16573156
TI  - [The changes of the muscular fiber phynotype at different condition of nerve
      injury].
AB  - OBJECTIVE: To observe the change of the muscular fiber phynotype at different
      condition of nerve injury. METHODS: Rabbits were used as an animal model in this
      study. The trigeminus and facial nerves of the animal were simultaneously severed
      (group 1) or only the latter was severed (group 2). The morphologic change of the
      muscular fibers was observed with histochemical methods; the tension of
      contraction and the threshold value of electrical stimulation were observed with
      electrical physiological methods. RESULTS: Trigeminus nerve play an important
      role in delaying muscular atrophy after facial nerve was severed. The atrophy
      degree of type II a and II b muscular fibers was less in group 2 than that in
      group 1. The change of type 1 muscular fibers was not affected by trigeminus
      nerve. New muscular fibers emerged in group 2. The tension of contraction and the
      threshold value of electrical stimulation were better in group 2 than that of in
      group 1. CONCLUSIONS: Sensory nerve could delay muscle atrophy after denervation.
      Sensory nerve should be repaired simultaneously when the motor nerve was sutured.
      The results of this study would facilitate clinical treatment for facial palsy.

PMID- 16573155
TI  - [Relationship between nonsyndromic cleft lip with or without cleft palate
      (NSCL/P) and genetic polymorphisms of MTHFR C677T and A1298C].
AB  - OBJECTIVE: To explore the relationship between nonsyndromic cleft lip with or
      without cleft palate (NSCL/P) and genetic polymorphism of MTHFR C677T and A1298C
      in Chinese population. METHODS: Case-control study design was employed. MTHFR
      genotypes were determined by polymerase chain reaction and restriction fragment
      length polymorphism techniques (PCR-RFLP). RESULTS: As to MTHFR C677T, 48
      heterozygous parents with an affected child were analyzed through case-parental
      control study using TDT (chi2 = 0. 02, P > 0.05). The genotype frequency and
      allele frequency of 76 NSCL/P cases and 60 controls were analyzed through case
      control study (chi2 = 9.91, P < 0.05). As to MTHFR A1298C, 27 heterozygous
      parents with an affected child were analyzed through case-parental control study
      using TDT (chi2 = 4.00, P < 0.05). The genotype frequency and allele frequency of
      76 NSCL/P cases and 60 controls were analyzed through case-control study (chi2 =
      4.42, P < 0.05). CONCLUSIONS: The genetic polymorphism of MTHFR C677T is
      associated with the development of NSCL/P, and the genetic polymorphism of MTHFR
      A1298C is a risk factor for NSCL/P in the Chinese population.

PMID- 16573157
TI  - [Combined superficial temporal fascial flap with free dermis-fat graft to
      reconstruct hemifacial atrophy].
AB  - OBJECTIVE: To introduce a method to reconstruct hemifacial atrophy (Romberg's
      disease). METHODS: Through a temporal incision, the compound grafts of pedicled
      superficial temporal fascial flap and free dermis-fat were inserted into the
      cheek to correct soft tissue depression on the face. The dermis-fat was harvested
      from gluteal crease site. RESULTS: 6 cases were treated with this technique. 3 to
      10 months' follow-up showed satisfactory results and few resorption of the
      compound grafts. CONCLUSIONS: The mentioned technique is simple and reliable in
      reconstructing bulk defects of the face.

PMID- 16573158
TI  - [Analysis of the complications following mandibular distraction using internal
      distractors].
AB  - OBJECTIVE: To investigate the causes and the prophylactic for the complications
      following mandibular distraction osteogenesis using internal distractors.
      METHODS: From 1997 to 2004, a total of 46 patients (61 sides) suffering from
      malformations or defects of mandible who underwent mandibular distraction
      osteogenesis were analyzed. The diseases included hemifacial microsomia in 27
      cases, congenital or acquired mandibular hypoplasia and micrognathia bilateral in
      8 cases and unilateral in 4 cases, electronical injury or postoperative
      mandibular defects in 3 cases, Treacher Collins syndrome in 2 cases, obstructive
      sleep apnea syndrome in 2 cases. RESULTS: Of them, 9 patients had postoperative
      complications, which included 3 patients had complications associated with
      distractors, local infection occurred in 2 cases, apertognathia of anterior teeth
      in 2 case, 2 patients had sinus of the skin of the lower lip. 9 patients had been
      aggressivly managed and obtained satisfactory results. CONCLUSIONS: The pivotal
      points to reduce complications are to understand the mechanism of mandibular
      distraction osteogenesis completely, and to be familiar with the anatomy of
      mandible and adjacent tissues. It is necessary to treat with it preoperatively
      and postoperatively.

PMID- 16573159
TI  - [The changes of micrangium density of the reverse-flow random flap with a
      superficial venous trunk: an experimental study using stereological methods].
AB  - OBJECTIVE: To study the effects of the superficial venous trunk (SVT) and its
      nourishing vessels on early revascularization of the reverse-flow random flap in
      order to provide theoretical evidences for clinical applications. METHODS: The
      morphologic changes of micrangium of the reverse-flow random flap with SVT and
      without SVT were observed at different phases and compared by optical microscopy
      and stereological methods. RESULTS: The micrangium density of the flaps with SVT
      and without SVT showed a tendency of increasing at 3 days after the operation. At
      5 to 10 days, the micrangium density of the flap with SVT was much higher than
      the flap without SVT. There was significant difference between the two groups,
      which was proved by the optical microscopy observation. CONCLUSIONS: This study
      suggests that SVT and its nourishing vessels could promote early
      revascularization of the flap after transplantation. The SVT can be of benefit to
      the survival of the reverse-flow random flap.

PMID- 16573160
TI  - [Study on the protective effects of ZnSO4 on rat flaps with ischemia reperfusion
      injury].
AB  - OBJECTIVE: To observe the protective role of the ectogenesis zinc in the rat flap
      with ischemia-reperfusion injury and study the mechanism. METHODS: An abdominal
      island flap was created in Wistar rats. 48 rats were randomly divided into three
      groups, 16 per group: the non-ischemia-reperfusion group, the ischemia
      reperfusion group and the ischemia-reperfusion (IR) group treated with zinc. The
      content of malondialdehyde (MDA) and the activity of myeloperoxidase (MPO) were
      measured. The expression of metallothionein (MT) was observed, and the image
      analysis was performed. The ultrastructure changes of the skin flap with ischemia
      reperfusion injury and the flap viability were observed. RESULTS: Compared with
      the IR group, at 1 h and 24 h of reperfusion, the level of MDA in the adding-zinc
      IR group decreased 11.3% and 33.2% (P < 0.05); the activity of MPO decreased
      14.2% and 22.7% (P < 0.05); the content of MT increased 41.5% and 44% ( P < 0.01)
      respectively. In the ischemia-reperfusion injury flaps, MT was located in the
      cytoplasm of many kinds of cells. The ultrastructure changes of the skin flap of
      the adding-zinc-IR group were slighter than those of the IR group. The flap
      viability in the adding-zinc-IR group increased 27.2% (P < 0.05). CONCLUSIONS: MT
      could be induced by ectogenesis zinc in the flap of rats. The flap with ischemia
      reperfusion injury was protected by MT through protecting the cells in the flap.

PMID- 16573161
TI  - [Restore hand's function after electric injuries at the wrist by a free composite
      flap].
AB  - OBJECTIVE: To introduce a new free composite flap for the treatment of electric
      injuries of hands, which can repair the skin, blood vessels, tendons and nerves
      injuries in just one operation. It may improve the prognosis of electric hand
      injuries. METHODS: 5 patients with electric injuries at wrist were treated by the
      free composite flap. The procedure is followed: The composite flap was harvested
      from medial lateral crural skin flap. Its blood supply was from tibial posterior
      vessels. The perforans arteries to flap and the branches to plantaris were
      preserved, and the nerve suralis and tendon plantaris were compound into the flap
      by carefully dissection of crural fascia. At the same time, 3-4 tendons of
      extensor digitorum longus were inserted into the superficial crural fascia. Thus,
      blood vessels, nerves and tendons were combined into the flap before
      transplantation. The composite flap was then transplanted into the recipient site
      of the electric injuries of hand to repair the long defects of the skin, blood
      vessels,nerves and tendons in one operation. The evaluation methods of the
      prognosis are the follows: the active motion function of finger was assessed by
      flexion and extension function of the fingers. The sensibility function was
      tested by the standards recommended by British Medical Association. RESULTS: The
      patients were followed up from 3 to 12 months. All the flaps were survived. Six
      months after operation, the flexion distance from tip to palmar crease and
      extension distance from tip to horizontal level of 3 patients were 4-5 cm and 3-4
      cm respectively, and the other 2 patients were recovered from 6 cm and 5 cm to 4
      cm and 4 cm respectively. The sensibility of finger skin reached to S2 level, and
      skin temperature rose. CONCLUSION: The free medial lateral crural composite flap
      was an ideal one to cure electric injuries at wrist, for it repairs skin, nerves,
      vessels and tendons defects in just one operation.

PMID- 16573162
TI  - [Clinical applications of the neurocutaneous axial flap pedicled with perforating
      vessels].
AB  - OBJECTIVE: To report the operative technique and clinical results of the
      neurocutaneous vascular axial flap with perforating vessels as its pedicle.
      METHODS: An axial skin flap was designed along the axis of small paraneural
      vessels that was close to a concomitant cutaneous nerve. The cutaneous
      perforating branches of major arteries were used as the pedicle, which provided a
      rotation arc for the flap to cover the defects in the distal site of extremities.
      43 neurocutaneous vascular axial flaps were transferred, including 13 sural
      neurocutaneous axial flaps (30 cm x 12 cm to 16 cm x 8 cm) supplied by
      perforating branches of the peroneal vessel; 9 saphenous neurocutaneous axial
      flaps (15 cm x 8 cm to 5 cm x 4 cm) with posterior tibial perforators as the
      pedicle; 8 posterior antebrachial neurocutaneous axial flaps (16 cm x 6 cm to 10
      cm x 4 cm) based on the dorsal branch of the anterior interossea vessel and 13
      reversed neurocutaneous axial flaps (6.0 cm x 3.5 cm to 2.5 cm x 1.5 cm) on the
      dorsal hand pedicled with the perforators at the interdigital web space. RESULTS:
      42 flaps survived completely. One flap underwent venous congestion with necrosis
      on the distal one fourth of the flap. The color and texture of the flaps were
      good. The appearance and functional results were satisfactory as revealed by
      follow-up for 6 to 24 months. CONCLUSIONS: The modified operation combines the
      advantages of both the perforator flap and the neurocutaneous axial flap,
      enlarges the size of the flap and extends the scope of reconstruction. The flap
      is characterized with delicate designation, easy dissection and reliable blood
      supply. It is a good method in repairing the skin defects of the extremities.

PMID- 16573163
TI  - [The experimental study of mechanism of integrin in hypertrophic scar
      contracture].
AB  - OBJECTIVE: To study the mechanism of integrin in hypertrophic scar. METHODS:
      Fibroblasts from 10 samples of human hypertrophic scars was cultured, FQ-PCR
      assay was applied to detect mRNA expression of alpha-SMA in hypertrophic scar
      fibroblasts after integrin and FAK antibody blocking. RESULTS: mRNA of alpha-SMA
      in fibroblasts expressed obviously lower after integrin and FAK antibody blocking
      than that of control groups ( P < 0.05). CONCLUSION: Through accelerating the
      synthesis of alpha-SMA, integrin and FAK play an important role in contracture of
      hypertrophic scar.

PMID- 16573164
TI  - [Study on poly A site gene mutation of transforming growth factor-beta1 receptor
      type II between multiple and single site keloid].
AB  - OBJECTIVE: To investigate the pathogenesy deference between multiple and single
      site keloid by detecting gene mutation of Poly A site of transforming growth
      factor-beta1 receptor type II (TbetaR II). METHODS: Collecting 20 keloid samples
      (6 multiple sites keloid samples and 14 single site keloid samples) and
      extracting DNA from them; designing and synthesizing the primers of Poly A site,
      then amplifying T1beta II DNA by PCR, analyzing the single strand conformation
      polymorphism about the products of PCR. After purifying the product of PCR, the
      site and type of the mutation rate of Poly A site was sequenced directly on the
      automatic sequencing equipment. RESULTS: It had been found that the Poly A site
      of TbetaR II in keloid has deletion mutation, its mutation rate in multiple sites
      keloid was 50% (3/6), in single site keloid 7.1% (1/14). The mutation rate of
      Poly A site in multiple sites keloid was significant higher than that in single
      site keloid (P < 0.05) CONCLUSION: It has been supposed that there are some
      deference in pathogenesy between the multiple and the single site keloid.

PMID- 16573166
TI  - [A preliminary approach of covering corrugator with rectangle periosteous flap in
      rhytidectomy].
AB  - OBJECTIVE: To evaluate the aesthetic outcome after application of rectangle
      periosteous flap to cover corrugator. METHODS: On the basis of regular
      rhytidectomy, a inter-eyebrow periosteous flap is applied to cover the fascia
      flap of corrugator by means of turnover. This manipulation helps to separate the
      skin from the muscle and prevent the re-adherence between the skin and muscle.
      RESULTS: The approach was applied on 15 cases. The follow-up ranged from 6 months
      to 1 year. The results were satisfactory. CONCLUSIONS: The method is effective in
      elimination of inter-eyebrow crease.

PMID- 16573165
TI  - [Clinical study on keloid treatment with intralesional injection of low
      concentration 5-fluorouracil].
AB  - OBJECTIVE: To explore the effect of intralesional injection of low concentration
      5-fluorouracil (5-FU) on inhibition of angiogenesis of keloid. METHODS: 35
      patients with 51 keloids were treated with intralesional injection of 5-FU (2-5
      mg/ml) biweekly. After 3-6 times of injection, the keloids were treated with
      intralesional injection of corticosteroid. The average period of treatment was
      10.29 months. RESULTS: The efficacy of inhibiting keloid angiogenesis by low
      concentration of 5-fluorouracil was 96.77%. For the patients who were treated
      over 6 months with both 5-FU and corticosteroid, the total efficacy was 97.14%.
      Among them, 45.71% of keloids achieved complete remission, 48.57% mostly
      remission, 2.86% partial remission and 2.86% no remission. CONCLUSION: Inhibition
      of keloid angiogenesis with intralesional injection of low concentration of 5
      fluorouracil along with corticosteroid injection can achieve satisfactory result.

PMID- 16573167
TI  - [Relationship between expression of inducible nitric oxide synthase and
      proliferative potency of endothelium in hemangioma in infants].
AB  - OBJECTIVE: To investigate relationship between expression of inducible nitric
      oxide synthase (iNOS) and proliferative potency of endothelium in hemangioma
      (HM). METHODS: Immunohistochemical staining was used to detect expression of iNOS
      and Ki-67 protein in 49 cases of HM and 29 cases of vascular malformation (VM).
      RESULTS: Expressive rate of iNOS and Ki-67 protein of 49 cases of HM was 38% and
      (10.98 +/- 7.93)%. Expressive rate of iNOS and Ki-67 protein of 29 cases of VM
      was respectively 3% and (0.03 +/- 0.19)%. The expressive rate of iNOS and Ki-67
      protein of HM was significantly higher than that of VM (P = 0.001 and 0). The
      expressive rate of Ki-67 protein of HM of proliferative phase was (12.67 +/-
      7.65)% , which was significantly higher than that of HM of extinctive phase,
      (7.27 +/- 7.49)% (P = 0.028). CONCLUSIONS: Expression of iNOS and Ki-67 protein
      of HM is significantly higher than that of VM, and the proliferative potency of
      HM is significantly higher than that of VM.

PMID- 16573168
TI  - [The usage of inferior turbinate mucoperiosteal flap for repairing cleft palate].
AB  - OBJECTIVE: To evaluate a technique for closing the cleft of nasal aspect at the
      junction of the hard and soft palate and ensuring the wound healing well during
      the procedures of repairing broad cleft palate. METHODS: A inferior turbinate
      mucoperiosteal flap based posterior is designed and transposed to the junction of
      the hard and soft palate for decreasing the tension effectively and closing the
      cleft easily. RESULTS: All of the patients showed wound healing well and no
      distinct scars or palatal fistula. CONCLUSIONS: It is a simple and effective
      technique to decrease the tension and close the cleft of nasal aspect at the
      junction of the hard and soft palate with inferior turbinate mucoperiosteal flap.

PMID- 16573169
TI  - [The study of tissue-engineering bone for repair of segmental bone defects].
AB  - OBJECTIVE: To investigate the effect of tissue-engineering bone on repair of
      segmental bone defects. METHODS: Segmental bone defect of 21mm was created at
      sheep left metatarsus, which was then implanted with tissue-engineering bone (the
      experimental group) and pure porous beta-TCP (the control group) respectively.
      The bone defect in the blank group was left without treatment. After the sheep
      were sacrificed at the 1st, 3rd, or 6th month postoperatively, the samples were
      taken and examined by radiological, histological and biomechanical methods as
      well as scanning electron microscopy. The sheep in the blank group were
      sacrificed at the 6th month postoperatively. RESULTS: The osteoid tissue, woven
      bone and lamellar bone in the defect of the experimental group occurred earlier
      than in the control group. The new bone formed directly without through a
      cartilaginous intermediate in the experimental group, while the defect was
      repaired in a "creep substitution" way in the control group. At the 6th month,
      radiological and biomechanical tests revealed nearly complete repair of the bone
      defect of the experimental group, partial repair in the control group and non
      healing in the blank group. CONCLUSIONS: Tissue-engineering bone can repair bone
      defect, accelerating healing and without "creep substitution", which is a good
      option in repair of critical segmental bone defects. This study set up a basis
      for clinical applications in the future.

PMID- 16573170
TI  - [Effect of adeno-BMP7 transfection on osteogenesis of BMSCs].
AB  - OBJECTIVE: To study the effect of adeno-BMP7 transfection on the biology of bone
      marrow stromal cells (BMSCs). METHODS: Bone marrow was obtained from the goat.
      The BMSCs were isolated and cultured at the second passage. Once the cells
      attached and formed a monolayer with 70%-80% confluency, adeno-BMP7 (M.O.I. =
      100) was added to the cells. After three days, calcium node was examined with
      staining; cell-coral compound was replanted subcutaneously. RESULTS: With adeno
      BMP7 transfection, BMP7 expression was detected with Western-blot; big calcium
      nodes were observed with staining. New bone formation was enhanced, which was
      evaluated by X-ray and histological examinations. CONCLUSIONS: BMSCs transfected
      with adeno-BMP7 show much stronger osteogenic ability.

PMID- 16573171
TI  - [An experimental study on the culture of human oral mucosa epithelium using
      autologous serum].
AB  - OBJECTIVE: To investigate the biological properties of cultured human oral mucosa
      epithelium using autologous serum in order to provide a new material for tissue
      engineering urethra. METHODS: The cultured oral mucosa epithelium was
      respectively transplanted beneath the skin, above the deep fascia and in the
      wound of the athymic mice. The specimens were taken at 2, 3, 4, and 6 weeks
      posttransplantation, and processed for (1) immunofluorescence anti-HLA staining
      to determine graft acceptance, and (2) anti-human IV collagen and antihuman
      laminin immunohistochemical staining procedures to indicate the basement membrane
      formation. RESULTS: All the grafts survived and grew very well. The grafts were
      positive to anti-HLA. Collagen type IV and laminin were detected at the dermo
      epidermal junction in all groups from day 14, and increasing in density up to day
      21. CONCLUSIONS: he cultured human oral mucosa epithelium by autologous serum
      could develop an excellent functional epithelium tissue, which would be used to
      reconstruct urethra and repair wound.

PMID- 16573172
TI  - [Is the successful eradication of Helicobacter pylori sufficient for the healing
      of peptic ulcer?].
AB  - Helicobacter pylori has a major role in the pathogenesis of peptic ulcer disease.
      Cure of the infection is essential in ulcer healing, but an additional PPI
      therapy after completing eradication treatment is widespread in clinical
      practice. In the present work clinical studies evaluating peptic ulcer healing
      followed or not by PPI treatment after eradication therapy were analyzed. The
      results of these trials are concordant that only a minority of patients with
      duodenal ulcer would benefit from prolonged acid suppressive treatment, a
      successful eradication therapy (that counts for a large proportion) is
      sufficient. There are less data available concerning gastric ulcer: successful
      eradication is also essential to ulcer healing and to avoid relapse, however it
      seems that post-eradication PPI therapy might be beneficial.

PMID- 16573174
TI  - [Current concepts in the genetics of hereditary and sporadic colorectal cancer
      and the role of genetics in clinical practice: sporadic and IBD-associated
      colorectal tumors, significance of genetic tests in diagnosis, prognosis and
      assessment of chemotherapy outcome].
AB  - There has been a major improvement in our understanding in the area of the
      genetics of CRC in the last decade. Reason for this is partly that CRC has a
      strong hereditary trait and premalignant lesions are frequent and easily
      accessible. In the 1990-ies the mutations responsible for the adenoma-carcinoma
      sequence were discovered on after the other. In the second part of the review the
      authors discuss the genetic background of sporadic and IBD associated colorectal
      cancers as well as the role of genetics in the diagnosis, prognosis and
      prediction of therapy. Chromosomal instability (85%) and microsatellite
      instability with or without change in DNA methylation (15%) are the main
      mechanisms involved in the pathogenesis of sporadic colorectal cancers. It became
      evident that no ultimate mutations exist. Most of neoplasms are genetically
      heterogeneous, independent pathways and simultaneous tumorigenesis may exist
      within the same organ, also in the colon. Gene expression profile, clinical
      phenotype and prognosis may also vary according to the location. Similar genetic
      mutations may be found in IBD associated colorectal cancers, however, the typical
      sequence and importance of mutations is different. In future, fecal DNA testing
      may be an important screening tool for colorectal cancer; however, its routine
      use is still limited by its low sensitivity. Similarly, genetic investigation may
      play an increasing role in the prediction of prognosis, therapy and complication
      of chemotherapy. A more distant goal may be the individualization of the therapy.

PMID- 16573173
TI  - [The molecular biology of aging--therapeutic interventions?].
AB  - Aging is a complex mechanism of progressive and irreversible processes occurring
      to molecules, to cells and to the whole organism and ending with death. Genetic -
      so called "programmed" - factors and the combination of environmental
      interactions play the most important role in its development. Changes in
      macromolecules caused by free radicals, non-enzymatic glycosylation and apoptosis
      have a special role in the pathomechanism of aging. Endocrine and immune systems
      have also an important influence and control on the process. Those environmental
      effects, as for example irradiation, toxic chemicals, metal ions, free radicals
      play a determinant role in the development of aging. Diseases of old age should
      be distinguished from aging per se, although changes in old age increase the
      frequency of diseases. Those aging changes, which are associated with a
      generalized increase in mortality (but not with specific disease) would qualify
      as biomarkers of aging and would distinguish biological age from chronological
      age (passage of time). Because of increased average lifetime of people in the
      "western world", basic and clinical research in connection with aging and
      geriatrics has special importance in medicine. Better understanding of molecular
      and cellular mechanisms of aging could improve not only medical care of the
      elderly but could hold out also some hope in finding feasible solutions to slow
      down the aging process as well.

PMID- 16573175
TI  - [The biomedical periodicals of Hungarian editions--historical overview].
AB  - INTRODUCTION: The majority of Hungarian scientific results are published in
      international periodicals in foreign languages. Yet the publications in Hungarian
      scientific periodicals also should not be ignored. AIM: This study analyses
      biomedical periodicals of Hungarian edition from different points of view.
      METHODS: Based on different databases a list of titles consisting of 119 items
      resulted, which contains both the core and the peripheral journals of the
      biomedical field. These periodicals were analysed empirically, one by one:
      checking out the titles. RESULTS: 13 of the titles are ceased, among the rest 106
      Hungarian scientific journals 10 are published in English language. From the
      remaining majority of Hungarian language and publishing only a few show up in
      international databases. Although quarter of the Hungarian biomedical journals
      meet the requirements, which means they could be represented in international
      databases, these periodicals are not indexed. 42 biomedical periodicals are
      available online. Although quarter of these journals come with restricted access.
      2/3 of the Hungarian biomedical journals have detailed instructions to authors.
      These instructions inform the publishing doctors and researchers of the
      requirements of a biomedical periodical. CONCLUSIONS: The increasing number of
      Hungarian biomedical journals published is welcome news. But it would be
      important for quality publications which are cited a lot to appear in the
      Hungarian journals. The more publications are cited, the more journals and
      authors gain in prestige on home and international level.

PMID- 16573176
TI  - [Iodine allergy--adverse reactions to contrast media].
AB  - Essential of iodine allergy is not well-known in clinical practice and it might
      be combined with the adverse reactions of intravascular contrast media which
      contain iodine. Definition of iodine allergy should be cleared up because serum
      also contains iodine. One should make a difference between iodine allergy and
      adverse reactions of contrast media. Physiological role and occurrence of iodine
      in the organism was reviewed, moreover, allergic reactions caused by iodine
      containing chemicals (iodine and tropomyosine allergy). The contrast medium types
      and their immediate and late reactions were considered together with the
      mechanism. According to the published data and author's own experience the iodine
      allergy should be considered as an iodine-protein complex allergy. The cause of
      adverse reactions of contrast media is the whole molecule and not the iodine
      content of it. No cross reaction can be observed between iodine and contrast
      media. Iodine allergy and contrast media reactions are entirely different
      phenomenons. It was referred to prevention and therapy, as well.

PMID- 16573177
TI  - Hitting the hot buttons-WIIFM?

PMID- 16573178
TI  - Effective advocacy: a team assessment.

PMID- 16573179
TI  - Blog this!

PMID- 16573180
TI  - In search of definition.

PMID- 16573181
TI  - Making sense of evidence-based dentistry.

PMID- 16573182
TI  - Avian influenza (bird flu) and dentistry. Interview by Nelson L. Rhodus.
AB  - Now is the time for dental health care professionals to plan and prepare for
      their response to a potential pandemic. All dental health care professionals
      should be vaccinated. Dentists should engage their entire practice teams in those
      discussions and contingencies. Dentists should become familiar with the national
      public health plan and comply with it. Dentists should be prepared for an illness
      in which the principles of prioritization of treatment, including deferring
      routine care and/or suspending care, might be needed. Dentists should obtain and
      provide accurate information and should not allow themselves to be swayed by
      media hype.

PMID- 16573183
TI  - When the walls come tumbling down a pathway to recovery: episode two.

PMID- 16573184
TI  - Intraoffice dating.

PMID- 16573185
TI  - What's a dentist to do? To say or not to say.

PMID- 16573186
TI  - High-mileage study of on-board diagnostic emissions.

PMID- 16573187
TI  - Impact assessment of waste management options in Singapore.
AB  - This paper describes the application of life cycle assessment for evaluating
      various waste management options in Singapore, a small-island city state. The
      impact assessment method by SimaPro is carried out for comparing the potential
      environmental impacts of waste treatment options including landfilling,
      incineration, recycling, and composting. The inventory data include gases and
      leachate from landfills, air emissions and energy recovery from incinerators,
      energy (and emission) savings from recycling, composting gases, and transport
      pollution. The impact assessment results for climate change, acidification, and
      ecotoxicity show that the incineration of materials imposes considerable harm to
      both human health and the environment, especially for the burning of plastics,
      paper/cardboard, and ferrous metals. The results also show that, although some
      amount of energy can be derived from the incineration of wastes, these benefits
      are outweighed by the air pollution (heavy metals and dioxins/furans) that
      incinerators produce. For Singapore, landfill gases and leachate generate minimal
      environmental damage because of the nation's policy to landfill only 10% of the
      total disposed wastes. Land transportation and separation of waste materials also
      pose minimal environmental damage. However, sea transportation to the landfill
      could contribute significantly to acidification because of the emissions of
      sulfur oxides and nitrogen oxides from barges. The composting of horticultural
      wastes hardly imposes any environmental damage. Out of all the waste strategies,
      the recycling of wastes offers the best solution for environmental protection and
      improved human health for the nation. Significant emission savings can be
      realized through recycling.

PMID- 16573188
TI  - Air pollution from a large steel factory: polycyclic aromatic hydrocarbon
      emissions from coke-oven batteries.
AB  - A systematic investigation of solid and gaseous atmospheric emissions from some
      coke-oven batteries of one of Europe's largest integrated steel factory (Taranto,
      Italy) has been carried out. In air monitoring samples, polycyclic aromatic
      hydrocarbons (PAHs) were consistently detected at concentrations largely
      exceeding threshold limit values. By means of PAHs speciation profile and
      benzo(a)pyrene (BaP) equivalent dispersion modeling from diffuse sources, the
      study indicated that serious health risks exist not only in working areas, but
      also in a densely populated residential district near the factory.

PMID- 16573189
TI  - Comparison of measured total suspended particulate matter concentrations using
      tapered element oscillating microbalance and a total suspended particulate
      sampler.
AB  - A comparison of the concentration of the total suspended particulate (TSP) matter
      measured by the tapered element oscillating microbalance (TEOM) monitor and the
      isokinetic TSP samplers developed at the University of Illinois was carried out
      in several types of confinement livestock buildings. In a majority of the
      measurements done, the dust concentration measured by the TEOM monitor was lower
      than the University of Illinois at Urbana-Champaign (UIUC) isokinetic TSP
      sampler; the TEOM monitor tended to underestimate the total dust concentration by
      as much as 54%. The difference in measurements can be attributed to the sampling
      efficiency of the TEOM monitor sampling head and the loss of some semivolatile
      compounds and particle-bound water because of heating of the TEOM monitor
      sampling stream to 50 degrees C. Although several articles in the literature
      supported the latter argument, this study did not investigate the effect of
      heating the sampling stream or the effect of moisture on the relative difference
      in dust concentration measurements. The model that best describes the
      relationship between the two methods was site specific, that is, the linear
      regression model was applicable only to four of the sites monitored. The measured
      total dust concentration in livestock buildings range from approximately 300 to
      4000 microg/m3; a higher correlation coefficient between TEOM-TSP and UIUC-TSP
      monitors was obtained in swine facilities than those obtained in a laying
      facility.

PMID- 16573190
TI  - Weekday/Weekend differences in ambient air pollutant concentrations in atlanta
      and the southeastern United States.
AB  - The authors quantified changes between mean weekday and weekend ambient
      concentrations of ozone (O3) precursors (volatile organic compounds [VOC], carbon
      monoxide [CO], nitric oxide, and oxides of nitrogen [NOx]) in Atlanta and
      surrounding areas to observe how weekend precursor emission levels influenced
      ambient O3 levels. The authors analyzed CO, nitric oxide (NO), and NO,
      measurements from 1998 to 2002 and speciated VOC from 1996 to 2003. They observed
      a strong weekend effect in the Atlanta region, with median daytime (6:00 a.m. to
      3:00 p.m. Eastern Standard Time) decreases of 62%, 57%, and 31%, respectively, in
      the ambient levels of NO, NOx, and CO from Wednesdays to Sundays, during the
      ozone season (March to October). They also observed significant decreases in
      ambient VOC levels between Wednesdays and Sundays, with decreases of 28% for the
      sum of aromatic compounds and 19% for the sum of Photochemical Assessment
      Monitoring Stations target compounds. Despite large reductions in O3 precursor
      levels on weekends, day-of-week differences in O3 mixing ratios in and near
      Atlanta were much smaller. Averaging overall O3-season days, the 1-hr and 8-hr
      mean peak daily O3 maxima on Sundays were 4.5% and 2.3% lower, respectively, than
      their mean levels on Wednesdays (median of 14 site differences), with no sites
      showing statistically significant Wednesday-to-Sunday differences. When
      restricted to high-O3 days (highest 3 peak O3 days per day of week per site per
      year), the 1-hr and 8-hr Sunday O3 mixing ratios were 11% and 10% lower,
      respectively, than their mean peak levels on Wednesdays (median of 14 site
      differences), with 6 of 14 sites showing statistically significant Wednesday-to
      Sunday differences. The analyses of weekday/weekend differences in O3 precursor
      concentrations show that different emission reductions than normally take place
      each weekend will be required to achieve major reductions in ambient ozone levels
      in the Atlanta area.

PMID- 16573191
TI  - Black carbon and polycyclic aromatic hydrocarbon emissions from vehicles in the
      United States-Mexico border region: pilot study.
AB  - The investigators developed a system to measure black carbon (BC) and particle
      bound polycyclic aromatic hydrocarbon (PAH) emission factors during roadside
      sampling in four cities along the United States-Mexico border, Calexico/Mexicali
      and El Paso/Juarez. The measurement system included a photoacoustic analyzer for
      BC, a photoelectric aerosol sensor for particle-bound PAHs, and a carbon dioxide
      (CO2) analyzer. When a vehicle with measurable emissions passed the system probe,
      corresponding BC, PAH, and CO2 peaks were evident, and a fuel-based emission
      factor was estimated. A picture of each vehicle was also recorded with a digital
      camera. The advantage of this system, compared with other roadside methods, is
      the direct measurement of particulate matter components and limited interference
      from roadside dust. The study revealed some interesting trends: Mexican buses and
      all medium-duty trucks were more frequently identified as high emitters of BC and
      PAH than heavy-duty trucks or passenger vehicles. In addition, because of the
      high daily mileage of buses, they are good candidates for additional study.
      Mexican trucks and buses had higher average emission factors compared with U.S.
      trucks and buses, but the differences were not statistically significant. Few
      passenger vehicles had measurable BC and PAH emissions, although the highest
      emission factor came from an older model passenger vehicle licensed in Baja
      California.

PMID- 16573192
TI  - Laboratory and field evaluation of instrumentation for the semicontinuous
      determination of particulate nitrate (and other water-soluble particulate
      components).
AB  - Studies conducted at the U.S. Environmental Protection Agency facility in
      Research Triangle Park, NC, and at a field study in Southern California have
      demonstrated the capability for the semicontinuous determination of particulate
      nitrate (and other water-soluble ionic species). Two instruments, an R&P Series
      8400N Ambient Particulate Nitrate Monitor (8400N) and an ion chromatography (IC)
      based prototype monitor developed at Texas Tech University, were evaluated both
      in the laboratory using aqueous standards and simulated ambient aerosols and in
      the field during a 3-week July 1-21, 2003) joint ambient comparison study with
      Brigham Young University and the South Coast Air Quality Management District
      (SCAQMD). The field study was conducted at the SCAQMD Rubidoux field site near
      Riverside, CA. During initial (before the field study) laboratory studies, both
      instruments were responsive to changes in the simulated aerosol concentration.
      However, potential problems were discovered involving both instruments during the
      laboratory-based studies both before and after the Rubidoux study, and these
      problems are currently being addressed. During the 3-week field study period, 15
      minute average particulate nitrate concentrations approaching 30 microg/m3 were
      observed. Because of malfunctioning IC components (concentrator columns) of the
      Texas Tech University prototype monitor, limited data were obtained from this
      instrument during the 3-week sampling period. Initial ambient comparisons show
      general agreement between the 8400N and IC-based prototype instrument for the
      semicontinuous determination of ambient particulate nitrate at lower nitrate
      concentrations (<15 microg/m3) and an underdetermination by the 8400N at higher
      concentrations (>15 microg/m3). A decreased molybdenum converter efficiency in
      the pulse analyzer of the 8400N discovered during postfield study laboratory
      evaluation may explain the negative bias observed at higher nitrate
      concentrations. Semicontinuous results obtained from U.S. Environmental
      Protection Agency-operated instruments were averaged and compared with integrated
      sampler results obtained by Brigham Young University and SCAQMD.

PMID- 16573193
TI  - Characteristics of Asian dust transport based on synoptic meteorological analysis
      over Korea.
AB  - Classification of synoptic patterns and their correlation with dust events over
      East Asia were performed by means of cluster analysis. The average linkage and K
      means clustering techniques were used to identify two major weather types during
      Asian dust events (ADEs; total 26 ADEs with 47 dusty days) of six spring seasons
      from 1996 to 2001. The first weather type mainly influenced neighboring Asian
      countries and frequently occurred with ADEs (approximately 23% of ADE cases). It
      mostly occurred under a surface high (low)-pressure system over the west (east)
      of the Korean peninsula coupled with an upper-level trough and cutoff low passage
      over the center of the Korean peninsula. It showed strong advection in the
      middle/ upper troposphere with both a high aerosol index and enhanced coarse
      particulate matter (PM) loading over Korea. In contrast, the second weather type
      was mostly associated with long distance or continental-scale transport and
      occurred less frequently with ADEs (approximately 15%). It appeared with an upper
      level trough and a cutoff low vertically connected with a surface low system that
      was formed by a strong cyclonic vortex over the north of the Korean peninsula.
      There were weak advection, low aerosol index, and low coarse PM concentration
      over the Korean peninsula during the second weather type. In addition, it was
      found to be mostly associated with the trans-Pacific transport of Asian dust to
      the western coast of North America.

PMID- 16573194
TI  - Comparison of European national legislation efficiency on the reduction of air
      pollutant emissions.
AB  - Since 1995, the Institute for Environment and Development in Portugal has
      obtained >300 stack samples from various point sources of Portuguese industries.
      A coherent database was made with the collected results. The limit values fixed
      by several European legal documents consulted, Portuguese, Spanish, French,
      Italian, and Dutch emission legislation, were applied to the Institute for
      Environment and Development stack sampling inventory (from 1995 to 2000) to
      evaluate the efficiency of these standards in promoting the control and reduction
      of atmospheric pollutants emissions, especially regarding nitrogen oxides, sulfur
      dioxide, and particulate matter. The conclusion was that the original Portuguese
      legislation was not restrictive enough and not very efficient regarding emissions
      reduction. In contrast, the Dutch and Italian legislations are quite restrictive
      but very efficient concerning emission control for the three pollutants analyzed.
      One of the outcomes of this study was the publication of a new law in Portugal
      regulating the emissions of atmospheric pollutants. The strategy of this
      emissions control law follows the conclusions found in this study including the
      concept of a mass flow threshold and different approaches depending on source
      dimension.

PMID- 16573195
TI  - Evaluation of ozone-nitrogen oxides-volatile organic compound sensitivity of
      Cincinnati, Ohio.
AB  - Ambient concentrations of ozone (O3), nitrogen oxides (NOx), total reactive
      nitrogen (NOy), nitric acid (HNO3), and hydrogen peroxide (H2O2) were measured
      during September 2003 at an urban site of Cincinnati, OH. The aim of this study
      was two-fold: to investigate whether O3 formation in this population exposure
      type site is NOx, sensitive or volatile organic compound (VOC) sensitive and to
      test the practicality of using two combined observational-based methods to
      identify the sensitivity of O3 formation in midlevel polluted locations. The
      evaluation of the indicator species: NOy, O3/NOy, O3/HNO3, H2O2/ HNO3, and
      O3/(estimated NOx reaction products), as well as the combined hypothesis testing
      analysis of the weekend/weekday (WE/WD) differences of 1-hr and 8-hr average
      maximum O3 and of the 6:00 a.m.-9:00 a.m. average nitric oxide and NOx
      concentrations, show evidence that Cincinnati is likely VOC sensitive. Average WE
      1-hr and 8-hr maximum O3, as well as duration of WE O3 accumulation, were not
      lower than the corresponding WD levels in spite of the observed significant
      reduction in NO, emissions on WE, a typical situation in VOC-sensitive locations.
      The possibility that the seasonal transition from summer to autumn could have
      influenced the results was also investigated through an exploratory analysis of
      the afternoon O3 maximum/NOx measured and of the WE/WD differences of peak O3 and
      morning average NO and NO, concentrations observed at this site from June through
      September 2003. The results suggest that a VOC-sensitive chemistry regime
      dominated along the summer season. The findings of this study suggest that
      additional reductions in regional NO, emissions in Cincinnati, a potential
      nonattainment area under the 8-hr O3 standard, may cause an increase in local O3.
      Future strategies to reduce O3 in Southwest Ohio should be further evaluated
      carefully. The combination of observational-based methods might provide a
      consistent complementary approach in the identification of the NO,-VOC sensitive
      characteristics of mid-to-moderate polluted urban areas.

PMID- 16573196
TI  - Effects of residence time distribution and packing on methanol oxidation in
      biotrickling filter.
AB  - The effects of residence time distribution (RTD) on biotrickling filter systems
      and the comparison of the maximum elimination capacity (EC) and poisoning limits
      as functions of loadings of two packing media, Celite Biocatalyst Carrier R-635
      and a subituminous coal, were studied. To alter the RTD patterns in the two
      reactor columns, two baffle designs were chosen. The RTD tests were done under
      dry conditions, over a range of airflow rates, with zero baffle, one baffle, and
      two baffles added into each column. Mixed culture from compost was used to
      acclimate the bed for the methanol removal efficiency study. No nutrients were
      added in the coal column. To study the poisoning limit, the inlet methanol
      concentration was randomly increased until a severe drop in removal efficiency
      occurred. From the RTD tests and the removal efficiency runs, which did not
      result in 100% conversion, number of tank-in-series (N) values, maximum EC
      values, and rate constants of each column with different baffle configurations
      could be obtained. Results from duplicate runs showed that addition of baffles
      decreased the N values of the columns and increased the back mixing in both
      systems. Maximum EC values, critical loadings, and poisoning limits also
      increased with increasing back mixing. Coal was superior to Celite Biocatalyst
      Carrier R-635 because it gave good conversions without additional nutrients. In
      all runs, the rate of methanol removal was controlled by a zero order process.

PMID- 16573197
TI  - The role of pressure drop and flow redistribution on modeling mercury control
      using sorbent injection in baghouse filters.
AB  - A mathematical model based on simple cake filtration theory was coupled to a
      previously developed two-stage mathematical model for mercury (Hg) removal using
      powdered activated carbon injection upstream of a baghouse filter. Values of the
      average permeability of the filter cake and the filter resistance extracted from
      the model were 4.4 x 10(-13) m2 and 2.5 x 10(-4) m(-1), respectively. The flow is
      redistributed during partial cleaning of the filter, with flows higher across the
      newly cleaned filter section. The calculated average Hg removal efficiency from
      the baghouse is lower because of the high mass flux of Hg exiting the filter in
      the newly cleaned section. The model shows that calculated average Hg removal is
      affected by permeability, filter resistance, fraction of the baghouse cleaned,
      and cleaning interval.

PMID- 16573198
TI  - Effect of humic substance on thermal treatment of chromium(VI)-containing latosol
      soil.
AB  - Latosol soils contaminated with chromium(VI) [Cr(VI)], which is hazardous, can be
      recycled as raw materials for porcelain and construction sectors if a proper
      thermal stabilization process is implemented. This study investigates how thermal
      treatment affects Cr behavior during the sintering of latosol and deorganic
      latosol samples; both samples are artificially contaminated with CrO3. Approaches
      including X-ray absorption spectroscopy, scanning electron microscopy, N2-based
      Brunauer Emmett Teller surface analyzer, thermogravimetric analyzer/differential
      scanning calorimeter, and the toxicity characteristic leaching procedure
      promulgated by Taiwan Environmental Protection Administration are used in this
      study. After drying the Cr(VI)-contaminated latosol (i.e., containing 37,120 mg
      of Cr/kg sample) at 105 degrees C, approximately 80% of the doped CrO3 is
      chemically reduced to Cr(OH)3 by a humic substance naturally existing in the
      soil. In contrast, in the organics-free CrO3-contaminated latosol dried at 105
      degrees C, only 9% of the doped CrO3 is reduced to Cr(OH)3. Heating the samples
      at 500 and 1100 degrees C transforms hazardous Cr(VI) into Cr(III) that is
      negligibly toxic; Cr2O3, which is insoluble, is detected as the most abundant Cr
      species. Moreover, formation of Cr2SiOs, which is suggested to relate to low Cr
      leaching, is only detected in the sample heated at 1100 degrees C. Surface
      morphology, surface area, and thermogravimetric analyzer/differential scanning
      calorimeter results demonstrate that thermal treatment at 1100 degrees C can
      incur considerable soil sintering/ melting if the humic substance in the soil has
      been heated off previously. Finally, Cr concentrations in the toxicity
      characteristic leaching procedure leachates collected from the samples thermally
      treated at 1100 degrees C for 4 hr are < or =0.21 mg of Cr L(-1) that are much
      less than the Taiwan Environmental Protection Administration regulatory limit (<5
      mg of Cr L(-1)); consequently, these two samples are nonhazardous, and they have
      the potential for resource recycling. Conversely, Cr concentrations in the
      leachates from all 500 degrees C and 105 degrees C samples are in the 25.6-1279
      mg L(-1) range.

PMID- 16573199
TI  - [Biology of influenza viruses].
AB  - An attempt is made to present out of a multitude of available data those that
      will allow an insight into the biology of the influenza viruses, in order to
      contribute to the understanding of the present situation of influenza virus
      infections and the risk of pandemic influenza. This short overview is based on
      several reviews presented by others, some own reviews and statements, as well as
      some recent publications in scientific journals.

PMID- 16573200
TI  - [Influenza viruses and intracellular signalling pathways].
AB  - It has been described in the last years that after influenza virus-infection a
      variety of intracellular signalling pathways have been induced. There are
      examples and suggestions how the viral replication cycle leads to the activation
      of intracellular signalling pathways. A variety of signalling pathways are
      activated after virus-infection as an alert-response against the invading
      pathogen that can be considered as an antiviral response of the host cell.
      Nevertheless, it was also shown, that viruses are able to suppress these cellular
      responses to assure their own replication. Moreover, viruses are also able to
      activate and misuse cellular signalling pathways for their own survival. The NF
      kappaB signalling pathway is an excellent example of these sceneries. Activation
      of the NF-kappaB signalling pathway mediated by the virus can partially be
      blocked by the NS1 protein to suppress a strong antiviral IFN alpha/beta
      response. At the same time the virus takes advantage of the remaining NF-kappaB
      activity for virus related apoptosis and for its own replication. This is a
      highly effective and economic way for the virus to control its replication
      without the need for specific viral inducers of cellular responses. This
      demonstrates, that there are no "all or nothing" reactions in the field of
      interactions of Influenza viruses with intracellular signalling pathways. In one
      situation cellular antiviral responses can be misused by the virus of its own
      replication and at another point the same signalling pathway may even be turned
      into a pro-viral activity. When the impact of a given signalling pathway on viral
      growth is evaluated these bivalent functions of these pathways should be taken in
      consideration. Nevertheless, a signalling pathway that supports viral growth is
      an excellent target for antiviral therapy (Ludwig et al. 2003).

PMID- 16573201
TI  - Palmitoylation of influenza virus proteins.
AB  - During and after their synthesis, the envelope proteins of influenza viruses are
      extensively modified by glycosylation, disulfide-bond formation, oligomerisation
      and proteolytical cleavage. These modifications have an enormous impact on
      folding and transport of the proteins to the plasma membrane and are also crucial
      for the infectivity and pathogenicity of the resulting virus particles. Here we
      summarize the results of 25 years of research on the linkage of fatty acids to
      proteins (palmitoylation), a modification we discovered with viral glycoproteins
      including the influenza virus spike proteins. The fundamental biochemistry of the
      attachment of fatty acids to the hemagglutinin (HA) and to the ion-channel M2 is
      described which has been instrumental in revealing similar modifications in
      cellular proteins. Finally, the functional consequences of palmitoylation for
      entry of viruses into target cells by HA-mediated membrane fusion and for
      assembly and release of virus particles from infected cells are discussed.

PMID- 16573202
TI  - Influenza virus infections in mammals.
AB  - The natural reservoir of all known subtypes of influenza A viruses are aquatic
      birds, mainly of the orders Anseriformes and Charadriiformes in which the
      infection is asymptomatic and the viruses stay at an evolutionary equilibrium.
      However, mammals may occasionally contract influenza A virus infections from this
      pool. This article summarizes: (i) natural infections in mammals including pigs,
      horses, marine mammals, ferrets, minks; (ii) results from experimental infections
      in several animal models including mice, ferrets, primates, rats, minks, hamsters
      and (iii) evidence for the increased pathogenicity of the current influenza A
      H5N1/Asia viruses for mammals. Several reports have shown that a number of
      mammalian species, including pigs, cats, ferrets, minks, whales, seals and
      finally also man are susceptible to natural infection with influenza A viruses of
      purely avian genetic make up. Among the mammalian species naturally susceptible
      to avian influenza virus the pig and the cat might exert the greatest potential
      public health impact. Despite numerous studies in animal and cell culture models,
      the basis of the extended host spectrum and the unusual pathogenicity of the
      influenza A H5N1 viruses for mammals is only beginning to be unraveled. Recently,
      also the transmission of equine influenza A virus to greyhound racing dogs has
      been documented.

PMID- 16573203
TI  - [Influenza virus infections in migrating waterfowl: results of a two year study
      in Germany].
AB  - In order to determine the actual prevalence of avian influenza viruses (AIV) in
      wild birds in Germany, extensive surveillance studies were carried out between
      March 2003 and January 2005. More than 3.000 samples of 79 different species of
      wild birds (migratory and resident birds) were taken and 1.151 established pools
      investigated. Samples came from 80 different regions of Germany. Forty AIV
      isolates representing 14 combinations of eight different hemagglutinin and eight
      neuraminidase subtypes, among them H5 and H7, were identified. All H5 and H7
      isolates were found to be of low pathogenicity. The overall incidence of the
      investigated pools based on virus isolation was 3,5 % for AIV, with considerable
      variability noted among species, season and location. All AIV were isolated from
      birds sampled in autumn. Most of the AIV isolates came from the resting or
      wintering areas of mallards breeding far north. This study adds to the
      understanding of the ecology of influenza viruses in wild birds and empahsizes
      the constant need for surveillance in times of an ongoing and expanding epidemic
      of highly pathogenic AI.

PMID- 16573204
TI  - [Classic fowl plague--a review].
AB  - Highly pathogenic avian influenza (HPAI) represents a severe form of generalized
      avian influenza which is characterized by a rapid and severe course of disease
      and a very high mortality. All poultry species are susceptible. Turkeys and
      chickens are most vulnerable. There are no pathognomonic symptoms or specific
      pathological alterations. The disease is caused by avian influenza virus strains
      of the subtypes H5 or H7. These viruses arise spontaneously from apathogenic
      progenitors by insertional mutation in the HA gene. Until recently, outbreaks of
      HPAI were rare events, however, they have been found to cause increasing losses
      over the past few years. Since 2003, a widespread occurrence of HPAI has been
      registered in southeast Asia, and some countries are endemically infected with
      HPAIV strain H5N1. In six countries this virus has also caused fatal human
      infections. This has sparked fears that this agent may be the progenitor of a new
      pandemic influenza virus. During summer 2005 the disease has slowly spread
      westward. Isolated outbreaks have been reported from Kazakhstan, Russia, Romania,
      Turkey, Croatia and Ukraine. Migratory birds have been tentatively accused for
      spreading the infection along their flyways.

PMID- 16573205
TI  - [Control and eradication strategies for classic fowl plague in Germany and the
      European Union].
AB  - The huge potential economic impact of highly pathogenic avian influenza (HPAI)
      substantiates specific and rigorous legal regulations worldwide. According to the
      O.I.E. Terrestrial Animal Health Code fowl plague is a notifiable disease.
      International trading activities concerning poultry and poultry products
      originating from countries with active HPAI are rigorously restricted. In EU
      member states directive 92/40/EEC subsumes measures against fowl plague and has
      been transferred into German legislation by the "Geflugelpest-Verordnung". These
      acts specify that vaccination against HPAI is principally prohibited. The aim of
      all sanctions is the extinction of disease and the eradication of the causative
      agent. However, HPAI viruses, exclusively belonging to subtypes H5 and H7, can re
      emerge de novo from progenitor viruses of low pathogenicity which are perpetuated
      in the wild bird population. An outbreak of HPAI requires prompt action by a
      stamping out strategy. Fast and accurate diagnosis, a strict stand-still and the
      culling of affected flocks are at the basis of success. In areas with a high
      density of poultry holdings preemptive culling and creation of buffer zones,
      devoid of susceptible poultry, may be neccessary. In these cases emergency
      vaccinations can be considered as a supportive measure in order to limit mass
      culling. Vaccinations on merely prophylactic grounds, not being connected to
      acute outbreaks, should be avoided beware of selective pressures on the virus
      leading to antigenic drift and escape of vaccine-induced immunity. Instead, high
      standard biosecurity measures, particularly limiting direct and indirect contacts
      with wild birds, should be maintained.

PMID- 16573206
TI  - [Recombinant viruses of poultry as vector vaccines against fowl plague].
AB  - To help in the control of fowl plague caused by highly pathogenic avian influenza
      A viruses of hemagglutinin (HA) subtypes H5 and H7 several vaccines have been
      developed. A prophylactic immunization of poultry with inactivated influenza
      viruses in non-endemic situations is questionable, however, due to the impairment
      of serological identification of field virus-infected animals which hinders
      elimination of the infectious agent from the population. This problem might be
      overcome by the use of genetically engineered marker vaccines which contain only
      the protective influenza virus hemagglutinin. Infected animals could then be
      unambiguously identified by their serum antibodies against other influenza virus
      proteins, e.g. neuraminidase or nucleoprotein. For such a use, purified HA or HA
      expressing DNA vaccines are conceivable. Economically advantageous and easier to
      apply are modified live virus vaccines in use against other poultry diseases,
      which have been modified to express influenza virus HA. So far, recombinant HA
      expressing fowlpox virus (FPV) as well as infectious laryngotracheitis and
      Newcastle disease viruses have been asssessed in animal experiments. An H5
      expressing FPV recombinant is already in use in Central America and Southeast
      Asia but without accompanying marker diagnostics. Advantages and disadvantages of
      the different viral vectors are discussed.

PMID- 16573207
TI  - [Molecular characterization of human influenza viruses--a look back on the last
      10 years].
AB  - Influenza A (H3N2) viruses and influenza B viruses have caused more than 90% of
      influenza infections in Germany during the last then years. Continuous and
      extensive antigenic variation was evident for both the hemagglutinin (HA) and
      neuraminidase (NA) surface proteins of H3N2 and influenza B viruses. Molecular
      characterisation revealed an ongoing genetic drift even in years when the
      antigenic profiles of circulating strains were indistinguishable from those of
      the previous season. Retrospective phylogenetic studies showed that viruses
      similar to vaccine strains circulated one or two years before a given strain was
      recommended as vaccine strain. New drift variants of H3N2 viruses with
      significantly changed antigenic features appeared during the seasons 1997/1998
      and 2002/2003. Most influenza seasons were characterised by a co-circulation of
      at least two different lineages of H3N2 viruses. Genetic reassortment between
      H3N2 viruses belonging to separate lineages caused the different evolutionary
      pathways of the HA and viruses was responsible for the occurrence of H1N2 viruses
      during the season 2001/02. This new subtype has been detected only sporadically
      in Germany. The evolution of influenza B viruses was characterised by the re
      emergence of B/Victoria/2/87-lineage viruses and their co-circulation with
      viruses of the B/Yamagata/16/88-lineage. Reassortant B viruses possessing a
      Victoria/87-lineage HA and a Yamagata/88-like NA were predominant in Germany
      during 2002/03 and 2004/05.

PMID- 16573208
TI  - [Influenza pandemic planning].
AB  - In this article the most important properties of influenza A viruses are
      described to understand influenza pandemics. There are at least three
      possibilities: (1) By reassortment between an avian and the prevailing human
      influenza A virus viruses with a new surface are created, against which no
      neutralizing antibodies are present in the human population. Such a virus can
      spread immediately worldwide. (2) Viruses, which have been present in the human
      population some time ago, reappear and infect the new generation, which has not
      been in contact with this virus before. (3) An avian influenza virus crosses the
      species barrier to humans and forms there a new stable lineage. In relation to
      pandemic planning, the first possibility can be more or less excluded, since the
      now-a-days human influenza A viruses have evolved so far away from their original
      source, the avian influenza viruses, that the formation of a well-growing and
      well-spreading reassortant is practically not possible anymore. Point two is a
      dangerous possibility, in that, e.g., a human H2N2 virus could reappear, which
      had disappeared in 1968 from the human population. The third possibility is at
      the moment the most dangerous situation, if, e.g., a highly neurotropic H5N1
      virus from Southeast Asia crosses the species barrier to humans. An infection
      with such a pandemic virus presumably cannot be treated efficiently by
      antivirals. In such a situation only a rapid vaccination would be successful. In
      this respect in the last year important results have been obtained by using the
      reverse genetics. Meanwhile in about 50 countries there have been drawn up
      pandemic-preparedness plans.

PMID- 16573209
TI  - A new approach to an influenza life vaccine: haemagglutinin cleavage site mutants
      generated by reverse genetics.
AB  - A promising approach to reduce the impact of influenza is the use of an
      attenuated life virus as a vaccine. Using reverse genetics, a mutant of strain
      A/WSN/33 with a modified cleavage site within its haemagglutinin was generated
      which depends on proteolytic activation by elastase. Unlike the wild-type
      requiring trypsin, this mutant is strictly dependent on elastase. Both viruses
      grow equally well in cell culture in the presence of the respective protease. In
      contrast to the lethal wild-type, the mutant is entirely attenuated in mice at a
      virus dose of 10(6) pfu. At a dose of 10(5) pfu it induced complete protection
      against lethal challenge. This approach allows the conversion of any epidemic
      strain into a genetically homologous attenuated virus.

PMID- 16573210
TI  - Does satiation close the open economy?
AB  - Pigeons responded on fixed-interval and fixed-ratio food schedules during
      sessions of extended duration. Pause lengths from the beginning of the session,
      when the subjects were hungry, resembled those found in open economies, whereas
      pause lengths from the end of the sessions, when the subjects were close to
      satiation, resembled those from closed economies. A model of motivation captured
      key features of the data, suggesting that a changing level of hunger is a causal
      factor in the behavioral differences observed between open and closed economies.
      Behavioral theories may provide a parsimonious alternative to economic theories
      in accounting for such effects.

PMID- 16573211
TI  - Dynamics of temporal discrimination.
AB  - The purpose of this research was to describe and explain the acquisition of
      temporal discriminations, transitions from one temporal interval to another, and
      asymptotic performance of stimulus and temporal discriminations. Rats were
      trained on a multiple cued interval (MCI) procedure with a head entry response on
      three signaled fixed-interval schedules of reinforcement (30, 60, and 120 sec).
      They readily learned the three temporal discriminations, whether they were
      presented simultaneously or successively, and they rapidly adjusted their
      performance to new intervals when the intermediate interval was varied daily.
      Although exponential functions provided good descriptions of many measures of
      temporal discrimination, different parameter values were required for each
      measure. The addition of a linear operator to a packet theory of timing with a
      single set of parameters provided a quantitative process model that fit many
      measures of the dynamics of temporal discrimination.

PMID- 16573212
TI  - Resistance to interference in complex negative patterning.
AB  - Resistance to interference was examined in rats that received a complex negative
      patterning discrimination in which XA and XB were followed by food reinforcement
      and XAB was not Retention of the discrimination was evident after separate
      reinforcement of both A and B (Experiment 3), but not after reinforcement of
      either AB (Experiments 1 and 3) or XAB (Experiments 2 and 3). These data suggest
      that complex negative patterning discriminations are acquired configurally and
      that the relative similarity of the original discrimination and subsequent
      interference trials dictates the final degree of retention observed.

PMID- 16573213
TI  - Identity concept formation during visual multiple-choice matching in a harbor
      seal (Phoca vitulina).
AB  - Identity concept formation was tested in a harbor seal using a visual multiple
      choice matching-to-sample task. The seal was first trained on a two-alternative
      matching task. After criterion (> or =80% correct choices in two successive
      sessions) was reached with two sets of two stimuli (Figure 3, Blocks A and B),
      stimulus sets were enlarged to six objects (Blocks C-G). After the seal reached
      criterion immediately with two successive sets (Blocks F and G), multiple-choice
      matching was introduced, first using stimulus sets of four familiar objects
      (Blocks H-M). After the seal reached the criterion immediately with two
      successive sets (Blocks L and M), completely new objects were used in two further
      stimulus sets (Blocks N and O). The seal immediately applied the matching rule in
      all four sessions (> or =80% correct choices). In two further sessions with
      problems composed of all 38 familiar stimuli, the seal again reached the
      criterion (Block P). In the final, transfer session, 20 new problems were
      composed of 80 unknown stimuli (Block Q). The seal immediately applied the
      matching rule in these one-trial tests, showing that harbor seals can
      conceptualize complex visual information.

PMID- 16573214
TI  - Trace and long-delay fear conditioning in the developing rat.
AB  - In two experiments with rats, we examined the developmental emergence of
      conditioned freezing following trace and short-delay conditioning and also
      included a long-delay comparison group. In the short-delay and trace groups, a 10
      sec conditioned stimulus (CS) was paired with shock; for the trace rats, a 10-sec
      trace interval followed CS termination. The long-delay groups received a 20-sec
      CS paired with shock, to equate for the longer interstimulus interval (ISI) in
      the trace group. Trace conditioning emerged later in development than did short
      delay conditioning (see Moye & Rudy, 1987). Importantly, long-delay conditioning
      emerged in parallel with trace conditioning, at a similar time, and with similar
      strength. These findings suggest a role for the longer ISI, as opposed to the
      unfilled gap per se, in the late emergence of trace conditioning. The role of the
      hippocampus in trace conditioning and the possibility that young rats encode the
      temporal relationship between CSs and unconditioned stimuli are also considered.

PMID- 16573216
TI  - Modulation of an activity response with associative and nonassociative fear in
      the rat: a lighting differential influences the form of defensive behavior evoked
      after fear conditioning.
AB  - Rats confronted with the onset of a light gradient display a transient increase
      in locomotion called the activity response (AR) and a dark preference (Godsil &
      Fanselow, 2004). These experiments demonstrate that the magnitude of the AR can
      be blunted with Pavlovian fear-conditioning procedures via associative and
      nonassociative fear. Although manifested in decreased locomotion, the blunted AR
      effect was not due to increased freezing or immobility behaviors. Instead, rats
      displayed reduced rearing and an increase in a class of behaviors called
      stationary activity. These results suggest that the lighting differential
      supplied by the cue influences the topography of defensive behavior and reduces
      the expression of freezing. This procedure provides a means by which to examine
      learned and unlearned defensive responses to the same stimulus.

PMID- 16573215
TI  - Ontogenetic forgetting of stimulus attributes.
AB  - The effects of age on the forgetting of stimulus attributes in a differential
      fear-conditioning paradigm were examined with 18- and 70-day-old rats tested in
      either the original conditions or shifted stimulating conditions at one of three
      retention intervals (1, 48, and 120 h). Adults displayed significant shifts at
      each retention interval, with those tested in the original context displaying
      greater fear than those tested in the shifted conditions. By contrast, by 48 h
      the 18-day-olds had forgotten the specific attributes of the training situation
      and began treating the two stimulating conditions as functionally equivalent
      (Experiment 1). In Experiment 2, we tracked the ontogenetic emergence of adult
      like memory for stimulus attributes and found a dramatic increase in memory
      capability by 25 days of age. Experiment 3 illustrated that the forgotten memory
      attributes of infants may be retrieved by administering a 90-sec cuing treatment
      10 min prior to the 48-h test Implications for the phenomenon of infantile
      amnesia are discussed.

PMID- 16573217
TI  - Amount of training effects in representation-mediated food aversion learning: no
      evidence of a role for associability changes.
AB  - Rats acquired aversions to food pellets when a previously trained signal for that
      food was paired with a toxin, but only after minimal signal-food training. After
      extensive signal-food training, signal-toxin pairings had no effect on food
      consumption even after manipulations that enhanced the associability of the
      signal. By contrast, conditioned responding to the signal retained its
      sensitivity to devaluation of the food reinforcer by food-toxin pairings after
      extensive training. These results suggest that the nature of associatively
      activated event representations changes over the course of training.

PMID- 16573218
TI  - Acquisition and extinction of facilitation in the C57BL/6J mouse.
AB  - Acquisition, extinction, and transfer of facilitation were explored in a series
      of experiments with C57BL/6J mice. With a procedure in which an auditory target
      was followed by food only in the presence of a visual facilitator, Experiments 1
      4 showed that the facilitator promoted magazine entries to the auditory target.
      This enhancement effect was eliminated by training the facilitator as a
      conditioned inhibitor (Experiments 1 and 3B). Enhancement was also reduced by
      nonreinforced presentations of the facilitator in a discrimination procedure
      (Experiment 1) and by simple nonreinforcement of the facilitator (Experiments 2,
      3A, and 4). In contrast to the results obtained with a facilitator, simple
      nonreinforcement of an inhibitor, a visual cue that had signaled when an auditory
      target would not be reinforced, did not reduce its ability to modulate responding
      to that target (Experiment 4). However, both the facilitator and the inhibitor
      were found to transfer their modulatory effects to other targets (Experiment 4).
      Finally, mice demonstrated no evidence of differential responding on a
      biconditional discrimination procedure in which one auditory target (A1) was
      reinforced in the presence of one visual stimulus (L1) but not in the presence of
      another (L2), and a different auditory target (A2) was reinforced in L2 but not
      in L1 (Experiment 5). The implications of these results for analysis of the
      function of a facilitator are discussed.

PMID- 16573219
TI  - Assisted suicide survives--narrowly.

PMID- 16573220
TI  - The AMA's charm offensive.

PMID- 16573221
TI  - EHRs: where do payers fit in?

PMID- 16573222
TI  - The rocky road to RHIOs.

PMID- 16573223
TI  - Personal health records: What's the status now?

PMID- 16573224
TI  - Checking your practice's vital signs.

PMID- 16573225
TI  - Teaching residents pays off for us.

PMID- 16573226
TI  - Every doctor should work as a waiter when you rely on tips, you quickly learn how
      to make the customer happy.

PMID- 16573227
TI  - Adding ancillaries. Flexible sigmoidoscopy.

PMID- 16573228
TI  - The AMA should learn from AARP.

PMID- 16573229
TI  - Scheduling drug reps online.

PMID- 16573231
TI  - Momma's legacy.

PMID- 16573230
TI  - Monitoring exam room wait times.

PMID- 16573232
TI  - How do your charts rate?

PMID- 16573233
TI  - If a patient claims sexual misconduct.

PMID- 16573234
TI  - The secretory capacity of a cell depends on the efficiency of endoplasmic
      reticulum-associated degradation.
AB  - Plasma cells, like other "professional" secretory cells, are capable of secreting
      thousands of proteins per second. To accomplish this impressive task, they
      contain a highly developed endoplasmic reticulum (ER), where newly synthesized
      proteins must fold and assemble to native structures before secretion. Protein
      biogenesis in the ER is coupled to a tight quality control schedule: aberrant
      molecules produced upon failure of the folding/oligomerization processes are
      retained in the ER, and eventually degraded by ER-associated degradation (ERAD)
      pathways. The activity of the ERAD machinery therefore needs to be adapted to
      variations in the load of the ER with cargo proteins. If ERAD is insufficient,
      misfolded proteins accumulate causing ER stress, apoptosis, and ER storage
      diseases. The capacity of ERAD also critically determines the efficiency of
      protein secretion. Here we summarize recent findings highlighting the role of
      ERAD in disease and development, particularly in professional secretory cells.

PMID- 16573235
TI  - Recognition and delivery of ERAD substrates to the proteasome and alternative
      paths for cell survival.
AB  - Endoplasmic reticulum-associated protein degradation (ERAD) is a protein quality
      control mechanism that minimizes the detrimental effects of protein misfolding in
      the secretory pathway. Molecular chaperones and ER lumenal lectins are essential
      components of this process because they maintain the solubility of unfolded
      proteins and can target ERAD substrates to the cytoplasmic proteasome. Other
      factors are likely required to aid in the selection of ERAD substrates, and
      distinct proteinaceous machineries are required for substrate
      retrotranslocation/dislocation from the ER and proteasome targeting. When the
      capacity of the ERAD machinery is exceeded or compromised, multiple degradative
      routes can be enlisted to prevent the detrimental consequences of ERAD substrate
      accumulation, which include cell death and disease.

PMID- 16573236
TI  - CPY* and the power of yeast genetics in the elucidation of quality control and
      associated protein degradation of the endoplasmic reticulum.
AB  - CPY* is a mutated and malfolded secretory enzyme (carboxypeptidase yscY,
      Gly255Arg), which is imported into the endoplasmic reticulum but never reaches
      the vacuole, the destination of its wild type counterpart. Its creation, through
      mutation, had a major impact on the elucidation of the mechanisms of quality
      control and associated protein degradation of the endoplasmic reticulum, the
      eukaryotic organelle, where secretory proteins start the passage to their site of
      action. The use of CPY* and yeast genetics led to the discovery of a new cellular
      principle, the retrograde transport of lumenal malfolded proteins across the ER
      membrane back to their site of synthesis, the cytoplasm. These tools furthermore
      paved the way for our current understanding of the basic mechanism of malfolded
      protein discovery in the ER and their ubiquitin-proteasome driven elimination in
      the cytosol (ERQD).

PMID- 16573237
TI  - The role of the ubiquitination machinery in dislocation and degradation of
      endoplasmic reticulum proteins.
AB  - Ubiquitination is essential for the dislocation and degradation of proteins from
      the endoplasmic reticulum (ER). How exactly this is regulated is unknown at
      present. This review provides an overview of ubiquitin-conjugating enzymes (E2s)
      and ubiquitin ligases (E3s) with a role in the degradation of ER proteins. Their
      structure and functions are described, as well as their mutual interactions.
      Substrate specificity and functional redundancy of E3 ligases are discussed, and
      other components of the ER degradation machinery that may associate with the
      ubiquitination system are reviewed.

PMID- 16573238
TI  - The role of p97/Cdc48p in endoplasmic reticulum-associated degradation: from the
      immune system to yeast.
AB  - Quality control mechanisms in the endoplasmic reticulum prevent deployment of
      aberrant or unwanted proteins to distal destinations and target them to
      degradation by a process known as endoplasmic reticulum-associated degradation,
      or ERAD. Attempts to characterize ERAD by identifying a specific component have
      revealed that the most general characteristic of ERAD is that the protein
      substrates are initially translocated to the ER and eventually eliminated in the
      cytosol by the ubiquitin-proteasome pathway. Hence, dislocation from the ER back
      to the cytosol is a hallmark in ERAD and p97/Cdc48p, a cytosolic AAA-ATPase that
      is essential for ERAD, appears to provide the driving force for this process.
      Moreover, unlike many ERAD components that participate in degradation of either
      lumenal or membrane substrates, p97/Cdc48p has a more general role in that it is
      required for ERAD of both types of substrates. Although p97/Cdc48p is not
      dedicated exclusively to ERAD, its ability to physically associate with ERAD
      substrates, with VIMP and with the E3 gp78 suggest that the p97/Cdc48Ufdl/Npl4
      complex acts as a coordinator that maintains coupling between the different steps
      in ERAD.

PMID- 16573239
TI  - The ins and outs of intracellular peptides and antigen presentation by MHC class
      I molecules.
AB  - MHC class I molecules present small intracellular generated fragments to the
      outside surveying immune system. This is the result of a series of biochemical
      processes involving biosynthesis, degradation, translocation, intracellular
      transport, diffusion, and many more. Critical intermediates and end products of
      this cascade of events are peptides. The peptides are generated by the
      proteasome, degraded by peptidases unless transported into the ER where another
      peptidase and MHC class I molecules are waiting. Unless peptides bind to MHC
      class I molecules, they are released from the ER and enter the cytoplasm by a
      system resembling the ERAD pathway in many aspects. The cycle of peptides over
      the ER membrane with the proteasome at the input site and peptidases or MHC class
      I molecules on the output site are central in the MHC class I antigen
      presentation pathway and this review.

PMID- 16573240
TI  - Entry of protein toxins into mammalian cells by crossing the endoplasmic
      reticulum membrane: co-opting basic mechanisms of endoplasmic reticulum
      associated degradation.
AB  - The catalytic polypeptides of certain bacterial and plant protein toxins reach
      their substrates in the cytosol of mammalian cells by retro-translocation from
      the endoplasmic reticulum (ER). Emerging evidence indicates that these proteins
      subvert the ER-associated protein degradation (ERAD) pathway that normally
      removes misfolded or unassembled proteins from the ER, to achieve
      retrotranslocation. Upon entering the ER lumen, the toxins are unfolded to be
      perceived as ERAD substrates. Toxins that retro-translocate from the ER have an
      unusually low lysine content to avoid ubiquitin-mediated proteasomal degradation.
      This allows the exported toxins to refold into the proteasome-resistant,
      biologically active conformation, and leads to cellular intoxication.

PMID- 16573242
TI  - Clinical education and cultural diversity in physical therapy: clinical
      performance of minority student physical therapists and the expectations of
      clinical instructors.
AB  - Clinical education is an integral part of preparation for the profession of
      physical therapy and the role of the clinical instructor is critical. The purpose
      of this study was to investigate clinical instructors' expectations of student
      physical therapists with different ethnic backgrounds and the clinical
      performance of the students as assessed using a modification of the Generic
      Abilities Assessment. For this study, individuals with a Caucasian ethnic
      background who were raised in the United States were considered as the majority.
      The remaining individuals (minority) were subdivided into five groups: African
      American, Hispanic, Asian/Pacific Islander, Caucasian from outside the United
      States, and Other. Clinical instructors reported their experiences with students
      from different ethnic backgrounds, their expectation of students' performance,
      and recollections of specific weaknesses in performance. From the 216 surveys
      distributed, 192 clinical instructors responded. Fifty-seven percent had
      supervised a minority student, with a mean of three students each. While 4%
      reported that they expected a higher standard from majority students, 17% noted a
      difference in performance between majority and minority students. Results from
      this study suggest that minority students would benefit from further preparation
      in communication and interpersonal skills but they are stronger than majority
      students in stress management and the effective use of time and resources.

PMID- 16573241
TI  - Innervation of the mammalian esophagus.
AB  - Understanding the innervation of the esophagus is a prerequisite for successful
      treatment of a variety of disorders, e.g., dysphagia, achalasia, gastroesophageal
      reflux disease (GERD) and non-cardiac chest pain. Although, at first glance,
      functions of the esophagus are relatively simple, their neuronal control is
      considerably complex. Vagal motor neurons of the nucleus ambiguus and
      preganglionic neurons of the dorsal motor nucleus innervate striated and smooth
      muscle, respectively. Myenteric neurons represent the interface between the
      dorsal motor nucleus and smooth muscle but they are also involved in striated
      muscle innervation. Intraganglionic laminar endings (IGLEs) represent
      mechanosensory vagal afferent terminals. They also establish intricate
      connections with enteric neurons. Afferent information is implemented by the
      swallowing central pattern generator in the brainstem, which generates and
      coordinates deglutitive activity in both striated and smooth esophageal muscle
      and orchestrates esophageal sphincters as well as gastric adaptive relaxation.
      Disturbed excitation/inhibition balance in the lower esophageal sphincter results
      in motility disorders, e.g., achalasia and GERD. Loss of mechanosensory afferents
      disrupts adaptation of deglutitive motor programs to bolus variables, eventually
      leading to megaesophagus. Both spinal and vagal afferents appear to contribute to
      painful sensations, e.g., non-cardiac chest pain. Extrinsic and intrinsic neurons
      may be involved in intramural reflexes using acetylcholine, nitric oxide,
      substance P, CGRP and glutamate as main transmitters. In addition, other
      molecules, e.g., ATP, GABA and probably also inflammatory cytokines, may modulate
      these neuronal functions.

PMID- 16573243
TI  - Associations between physical and psychological problems in a group of patients
      with stress-related behavior and somatoform disorders.
AB  - The research questions in this study were. How do patients with stress-related
      behavior and somatoform disorders assess symptoms and self-image compared to
      healthy individuals, and how are these assessments related to bodily resources,
      assessed with a physiotherapeutic body examination? The test group (n = 31)
      consisted of consecutive patients referred to a treatment center specializing in
      psychosomatic problems. Significant differences (p < or = 0.01) were found
      between the test and comparison group (n = 22) on all but two of the ten
      subscales of the Resource-Oriented Body Examination (ROBE II). This was also the
      case for all the subscales of The Symptom Checklist-90(SCL-90; comparison group n
      = 52), and for all but three of the eight clusters of the Structural Analysis of
      Social Behavior (SASB) (comparison group n = 52). For the patient group, the ROBE
      II subscale Increased respiratory control correlated significantly with the SCL
      90 subscales that measures Anger-hostility, Phobic anxiety, Paranoid ideation,
      with the Personality Severity Index (PSI) and with the SASB clusters Daydreaming
      and self-neglect, Self-indictment and oppression with r's between 0.38 and 0.50.
      Body examination with ROBE II might provide a useful assessment tool in patients
      whose stress-related problems appear to contain associations between
      psychological and physical problems.

PMID- 16573244
TI  - Reliability and smallest detectable change determination for serratus anterior
      muscle strength and endurance tests.
AB  - The purposes of this study were to determine inter-tester reliability, one-week
      test-retest reliability and smallest detectable difference (SDD) of serratus
      anterior muscle strength and endurance tests. Asymptomatic subjects were tested
      on an apparatus designed by the investigators. During strength testing, subjects
      performed isometric contractions recorded by a hand-held dynamometer. For
      endurance testing, subjects held a dumbbell of 15% of their body weight and
      performed repetitions until they became fatigued. Intraclass correlation
      coefficients (ICC) for the strength test revealed good inter-tester reliability
      (ICC2,3 = .90-.93) and good one-week test-retest reliability (ICC2,3 = .83-.89).
      For the endurance test, ICCs showed good inter-tester reliability (ICC2,1 = .71
      .76) but moderate one-week test-retest reliability (ICC2,1 = .59-.62). The SDDs
      at 68% confidence level ranged from 22.7 to 39.2 newtons for the strength test,
      and 11 to 20 repetitions for the endurance test. In summary, the technique used
      in the study is reliable for quantifying the SA muscle strength.

PMID- 16573245
TI  - Evaluation of a physiotherapeutic treatment intervention in "Bell's" facial
      palsy.
AB  - The aim of this study was to evaluate a physiotherapeutic treatment intervention
      in Bell's palsy. A consecutive series of nine patients with Bell's palsy
      participated in the study. The subjects were enrolled 4-21 weeks after the onset
      of facial paralysis. The study had a single subject experimental design with a
      baseline period of 2-6 weeks and a treatment period of 26-42 weeks. The patients
      were evaluated using a facial grading score, a paresis index and a written
      questionnaire created for this study. Every patient was taught to perform an
      exercise program twice daily, including movements of the muscles surrounding the
      mouth, nose, eyes and forehead. All the patients improved in terms of symmetry at
      rest, movement and function. In conclusion, patients with remaining symptoms of
      Bell's palsy appear to experience positive effects from a specific training
      program. A larger study, however, is needed to fully evaluate the treatment.

PMID- 16573246
TI  - Thoraco lumbar junction syndrome: a case report.
AB  - This case report describes a 46-year-old female who experienced symptoms of low
      back pain with pain radiating into the right gluteal area. Initial intervention
      addressed mechanical dysfunction at the lumbosacral junction. Reduction in
      symptoms was observed following manual therapy procedures that addressed the
      lumbosacral junction; however, the right gluteal pain persisted with recurrence
      of back pain. Subsequent examination revealed non-neutral dysfunction at the
      thoracolumbar junction. Treatment was continued with manual therapy procedures
      that addressed facet restriction and soft tissue dysfunction in the thoracolumbar
      junction. A marked relief in symptoms was reported thereafter, with a decrease in
      right gluteal pain and improved functional ability. The anatomical and clinical
      relevance to this scenario is described. The thoracolumbar junction is described
      as a predominant contributor to the symptomatology. Its complementary role to the
      lumbosacral junction is enumerated.

PMID- 16573247
TI  - Some thoughts on providing effective mental health critical care for police
      departments after Line-of-Duty Deaths.
AB  - There is no more stressful or emotionally painful event in the professional lives
      of police officers than a fellow officer's Line-of-Duty Death (LODD). In response
      to a LODD, crisis teams must apply Critical Incident Stress Management (CISM)
      techniques in a systematic, organized, and responsible manner. Newly formed
      crisis teams are particularly vulnerable to choosing inappropriate tactics in
      complex situations. This article provides a strategic framework within which
      teams can work with police departments after a LODD. It includes cautionary
      information in connection with problematic situations and mistakes that can
      occur. Special modifications to the LODD debriefing process are recommended.

PMID- 16573248
TI  - Caplan, community, and Critical Incident Stress Management.
AB  - Critical Incident Stress Management (CISM), a comprehensive crisis intervention
      program, is examined from the perspective of Community Psychology. Because CISM
      adheres to the 5 Principles of Community Psychology and was designed to be
      adopted and implemented as a systematic intervention embedded within an
      organization, it is argued that CISM is best understood and evaluated in context
      as a prevention program rather than simply a crisis intervention "treatment."
      Recommendations are made for evaluating CISM as a comprehensive intervention
      using an Action Research framework encompassing methodological pluralism and
      multiple stakeholders' definitions of success.

PMID- 16573249
TI  - Precipitants of psychiatric patient assaults on staff: three-year empirical
      inquiry of the Assaulted Staff Action Program (ASAP).
AB  - Patient violence toward health care staff is a complex function of person x event
      x environment model. Thirty-five years of research on the characteristics of
      patient assailants and staff victims has yielded no predictive markers and
      researchers are examining other possible components of the model. The
      precipitants, or motivation, for assaults is one area of inquiry. Although
      research to date has been sparse, acute psychosis, excessive sensory stimulation,
      and staff restrictions on patient behaviors (denial of services, privileges,
      etc.) appear to be common precipitants. This paper continued this inquiry over a
      three-year period. The most common precipitants were denial of services, acute
      psychosis, and excessive stimulation. No statistically significant interactions
      were obtained for patient / staff victim variables and these precipitants.

PMID- 16573250
TI  - Hospital based psychiatric emergency services: a guide to service delivery and
      clinical best practices.
AB  - Hospital based psychiatric emergency services play an integral role in the
      initiation of mental health and psychiatric service delivery worldwide. Whenever
      possible, hospital based psychiatric emergency services should be delivered in
      accordance to best practice standards. Unfortunately, no such standards exist
      internationally in the case of hospital based psychiatric emergency services.
      This paper represents an attempt to rectify this problem. International mental
      health and psychiatric literature pertaining to hospital based psychiatric
      emergency services was reviewed and a guide to service delivery and clinical best
      practice was generated.

PMID- 16573251
TI  - An investigation of potential Holocaust-related secondary traumatization in the
      third generation.
AB  - This study investigated whether grandchildren of Holocaust survivors placed in
      concentration camps were more prone to PTSD symptoms than grandchildren of Jewish
      non-immigrants (native-born) and grandchildren of Non-Jewish immigrants. It has
      been well established that PTSD symptoms can be transmitted from Holocaust
      survivor parents to their children. Previous research has not yet established
      whether an identical transmission of PTSD symptoms can occur from the second
      generation to the third. The measures employed in conducting this study were the
      Secondary Trauma Scale (STS), the Impact of Events Scale-Revised (IES-R), the
      State-Trait Anxiety Inventory (Form Y) (STAI), and a Modified Stroop Procedure
      which was comprised of colored Holocaust trauma-related words, positive words,
      neutral words and obsessive compulsive disorder words. Results indicate that all
      three groups exhibited longer response latency for the PTSD Holocaust-related
      stimuli card thereby indicating an increased sensitivity across all populations
      regardless of race or religion. The grandchildren of Holocaust survivors and the
      grandchildren of Non-Jewish immigrants scored significantly higher than the
      grandchildren of Jewish Americans on the Secondary Trauma Scale as well as the
      Avoidance subscale of the IES-R. This finding suggests a possible immigration
      effect for these groups. There were no other significant differences across the
      other measures employed in this study. These conclusions can be construed as
      persuasive evidence that, with respect to Holocaust-induced secondary trauma, the
      residual impact is diminished to such an extent by the third generation that the
      differences between grandchildren of Holocaust survivors and the overall
      population are statistically non-significant.

PMID- 16573252
TI  - Introduction to working with Animal Assisted Crisis Response animal handler
      teams.
AB  - Animal Assisted Crisis Response (AACR) is a discipline closely related to Animal
      Assisted Therapy (AAT), which gives crisis intervention teams, counselors,
      clergy, and other trained professionals an additional means with which to help
      people affected by crisis. AACR is a relatively new field, but can be effective
      when utilized as part of an overall incident response program. AACR teams can be
      used, for example, to establish rapport, build therapeutic bridges, normalize the
      experience, and act as a calming agent or as a catalyst for physical movement.
      Effective AACR requires a common language between the AACR teams and crisis
      counselors. The training requirements, versatility, limitations, and
      establishment of AACR teams are also addressed.

PMID- 16573253
TI  - Crusted scabies: a clinical review.
AB  - Crusted scabies, a rare variant of classical scabies, is a highly contagious
      condition in which the skin is infected with thousands to millions of mites. It
      can be defined as a generalized severe scabies infestation usually affecting
      immunocompromised patients. The diagnosis is becoming more relevant with the
      increasing use of immunosuppressive medications and the HIV epidemic. To date,
      more than 200 cases have been reported in the literature. We present a review of
      the pathogenesis, clinical manifestations, diagnostic considerations, and
      therapeutic options.

PMID- 16573254
TI  - Imatinib mesylate and dermatology part 2: a review of the cutaneous side effects
      of imatinib mesylate.
AB  - Cutaneous reactions to imatinib are common and occur in 9.5% to 69% of patients
      depending on the series reported. Maculopapular eruptions, erythematous
      eruptions, edema, and periorbital edema are the most common adverse events
      observed. Imatinib can also induce severe skin eruptions and generalized skin
      eruptions. Toxic epidermal necrolysis and Stevens Johnson syndrome has been
      linked to the use of imatinib. Imatinib has caused acute generalized
      exanthematous pustulosis. Purpuric vasculitis and mycosis fungoides-like
      reactions has occurred after imatinib use. Rarer side effects include:
      hypopigmentation, lichenoid reactions, pityriasiform eruptions, pityriasis rosea,
      psoriasis, reactivation or induction of porphyria cutanea tarda, neutrophilic
      eccrine hidradenitis, Sweet's syndrome, erythema nodosum, EBV-positive cutaneous
      B-cell lymphoproliferative disease, possible induction of squamous cell, hyaline
      cell syringomas, follicular mucinosis, pseudolymphoma-type drug eruptions, and
      malpighian epitheliomas. Most cutaneous eruptions caused by imatinib do not
      necessitate discontinuance of imatinib and are usually self limited, despite
      continued treatment. Administration of oral or topical corticosteroids can
      ameliorate some of imatinib's cutaneous side effects.

PMID- 16573255
TI  - Combination topical therapy for the treatment of psoriasis.
AB  - Dermatological research continues to move toward the goal of developing an
      effective psoriasis treatment that would rapidly clear lesions and provide long
      term freedom from visible signs and symptoms. Currently, topical corticosteroids
      remain a pivotal treatment due to their effective anti-inflammatory properties;
      however, potential adverse effects associated with chronic application limit long
      term continuous therapy. Vitamin D analogues provide another mechanism of action,
      reducing lesions through effects on both keratinocytes and on the cytokine
      environment. A topical combination of corticosteroid and vitamin D derivative
      appears to provide a balanced approach to psoriasis treatment. The development of
      clobetasol propionate foam 0.05% (clobetasol propionate foam/Olux) offers a
      convenient topical corticosteroid that can be used concomitantly, that is,
      immediately followed by application of calcipotriene ointment 0.005% (Dovonex).
      This regimen has been shown to offer an increased short-term efficacy compared
      with either agent alone. Continued application of calcipotriene ointment on
      weekdays supplemented by long-term clobetasol propionate foam pulse therapy on
      weekends appears to provide an enhanced maintenance of remission compared with
      calcipotriene monotherapy.

PMID- 16573257
TI  - Esophagitis due to tetracycline and its derivatives in dermatology patients.
AB  - Medication induced esophagitis (MIE) has been reported in dermatology patients
      taking tetracycline antibiotics. The symptoms of esophagitis, preventable with
      proper instruction, can create morbidity and lead to increased costs for
      patients. Our study sought to quantify the incidence of MIE in patients taking
      tetracycline antibiotics and to investigate how these patients develop MIE. A
      cross-sectional questionnaire survey was given at outpatient dermatology clinics.
      Ninety-three surveys from patients who had taken tetracycline antibiotics and 48
      surveys from a control group were analyzed. Incidence of esophagitis symptoms
      (difficulty or pain with swallowing) was measured in both survey and control
      groups. We found that esophagitis is significantly more common in patients taking
      tetracycline and its derivatives as compared with a control group (p<.03).
      Patients should be counseled to take tetracycline antibiotics in an upright
      position with a large amount of fluid and to report esophagitis symptoms to the
      prescribing physician.

PMID- 16573256
TI  - A multicenter, randomized, vehicle-controlled clinical study to examine the
      efficacy and safety of MAS063DP (Atopiclair) in the management of mild to
      moderate atopic dermatitis in adults.
AB  - BACKGROUND: MAS063DP cream has received marketing authorization in the US and the
      European Union for symptom relief of atopic dermatitis (eczema) and contact
      dermatitis. DESIGN: A multicenter, randomized, vehicle-controlled, phase IV study
      was completed in the US. METHODS: 218 patients aged 18 to 84 years joined this 50
      day study. Patients self-administered MAS063DP cream (N=145) or vehicle cream
      (N=73) 3 times per day to affected areas and those areas prone to be affected.
      The primary endpoint for efficacy was the change in EASI at Day 22 of treatment,
      comparing the 2 treatment groups. Secondary outcomes included EASI scores at
      other time points, IGA, pruritus (100mm VAS), % BSA, and the need for rescue
      medication. RESULTS: MAS063DP was statistically (p<.0001) more effective than
      vehicle in all outcomes at all time points. The incidence of rash was 2.1% in the
      MAS063DP group versus 5.5% in the vehicle group. Only 2 patients discontinued
      MAS063DP due to an adverse event. CONCLUSION: MAS063DP cream was confirmed to be
      a safe and effective treatment for mild to moderate atopic dermatitis in adults.

PMID- 16573258
TI  - Sustained efficacy and safety of infliximab in psoriasis: a retrospective study
      of 73 patients.
AB  - BACKGROUND: Infliximab inhibits T-cell activation by binding tumor necrosis
      factor-alpha (TNF-alpha). This medication is widely used in the US for treatment
      of psoriasis as an off-label indication. The durability of its effect is largely
      unknown. OBJECTIVE: To assess the proportion of patients still on infliximab 12
      months after initiation of therapy for psoriasis. METHODS: Retrospective chart
      review analysis of 73 patients with psoriasis treated with infliximab for at
      least 12 months or those who experienced treatment failure in less than 12
      months. The point where infusions were deemed to no longer be efficacious was
      determined by physician's global assessment (PGA). RESULTS: Of 73 patients who
      started infliximab at least 12 months prior to this chart review, 22 (30.1%) had
      discontinued treatment secondary to loss of efficacy. Thirty seven patients
      (50.7%) had no loss of efficacy and continued to receive infusions. Two patients
      (2.7%) discontinued due to loss of efficacy after greater than 12 months. Of the
      22 patients who discontinued treatment due to loss of efficacy, 2 were on
      concomitant methotrexate (5-7.5 mg/wk) therapy. Of the 37 patients still
      receiving treatment with no loss of efficacy at 12 months, 3 patients were on
      concomitant methotrexate therapy. Five patients (6.8%) discontinued secondary to
      minor adverse events: sinus infection (1), acne (1), fever (1), arthralgia (1),
      and transient rash (1). Three patients (4.1%) discontinued due to major adverse
      events: reactivation of tuberculosis (1), breast cancer (1), and gastrointestinal
      bleeding (1). One patient discontinued infliximab secondary to concerns of
      possible lymphoma risk (though there were no signs of symptoms of disease on
      examination), and 3 patients discontinued due to insurance concerns. CONCLUSION:
      Infliximab treatment resulted in significant improvement in psoriasis, with 37
      out of 73 patients (50.7%) experiencing no loss of efficacy. This longitudinal
      retrospective chart review demonstrates continued benefit of infliximab infusions
      in about half of patients after 1 year, though a notable percentage (30.1%)
      experienced loss of efficacy as determined by physician's global assessment (PGA)
      and a number of others discontinued due to adverse events or insurance
      difficulty.

PMID- 16573259
TI  - Tazarotene versus tazarotene plus clindamycin/benzoyl peroxide in the treatment
      of acne vulgaris: a multicenter, double-blind, randomized parallel-group trial.
AB  - Topical retinoids offer highly effective treatment for both inflammatory and non
      inflammatory acne, with tazarotene demonstrating greater efficacy than other
      topical retinoids. A multicenter, double-blind, randomized, parallel-group trial
      has been performed to evaluate whether the adjunctive use of clindamycin/benzoyl
      peroxide could enhance the efficacy of tazarotene still further. Patients with
      moderate to severe inflammatory acne applied tazarotene 0.1% cream each evening
      and were randomly assigned to morning applications of vehicle gel or a ready-to
      dispense formulation of clindamycin 1%/benzoyl peroxide 5 % gel containing 2
      emollients. Tazarotene/clindamycin/benzoyl peroxide achieved a significantly
      greater reduction in comedo count than tazarotene monotherapy and, among patients
      with a baseline papule plus pustule count of > or =25 (the median value), a
      significantly greater reduction in inflammatory lesion count. The combination
      therapy was also at least as well-tolerated as tazarotene monotherapy. The
      adjunctive use of clindamycin/benzoyl peroxide gel with tazarotene cream promotes
      greater efficacy and may also enhance tolerability. Any improvements in
      tolerability could be due to the emollients in the clindamycin/benzoyl peroxide
      gel formulation.

PMID- 16573260
TI  - Efficacy and safety of the topical sensitizer squaric acid dibutyl ester in
      Alopecia areata and factors influencing the outcome.
AB  - BACKGROUND: Immunotherapy with sqauric acid dibutyl ester (SADBE) is a well
      accepted therapy for alopecia areata. OBJECTIVE: To study efficacy, safety, and
      factors influencing the outcome in the treatment of alopecia areata. METHOD:
      During a 4-year period, 70 patients of alopecia areata, unresponsive to
      conventional therapies, were treated with SADBE for a period of 4 months and
      thereafter depending on the response with initial therapy. The percent scalp hair
      loss was calculated using "Severity of Alopecia Tool" (SALT) score before and
      after the therapy. RESULTS: Out of 70 patients, 6 were lost to follow-up and 4
      could not develop sensitization; therefore, data of 60 patients was available for
      analysis. The overall success rate was 43%. In patients with <50% scalp
      involvement; the success rate was better (68%) than in those with >50%
      involvement (29%). The response was better in patients with late onset and
      shorter duration of disease. Family history of alopecia areata or other
      autoimmune diseases, personal or family history of atopy, presence of auto
      antibodies in serum, and presence of nail changes were associated with poorer
      prognosis. Out of 26 patients who responded, relapse occurred in 21 (81%)
      patients. CONCLUSION: In conclusion, SADBE is an effective and well-tolerated
      mode of therapy in Indian patients of AA, although the long-term results of SADBE
      were not encouraging.

PMID- 16573261
TI  - Gel vehicles are not inherently more irritating than creams.
AB  - BACKGROUND: It has been thought that topical gels are inherently more irritating
      than topical creams. Nevertheless, the irritancies of topical products are
      potentially quite variable, and a priori assumptions about relative irritancy of
      gels versus creams may not be accurate. PURPOSE: To determine whether a
      metronidazole gel formulation is more or less irritating to the skin compared to
      metronidazole creams. METHODS: A total of 32 normal, healthy volunteers were
      tested using irritancy patches with 0.75% metronidazole gel and cream, 1%
      metronidazole cream, and petrolatum (used as the "negative control"). Blinded
      observers evaluated the application sites for signs of irritancy. A numerical
      score was assigned to these irritancy patch sites each day for 21 days, or until
      significant irritation developed, and cumulative irritancy scores were calculated
      for the study period. A mixed model of variance analysis was performed. RESULTS:
      After 21 days of evaluation, analysis of the mean cumulative irritancy scores for
      each of the agents used showed there to be no statistical difference in irritancy
      potential between the metronidazole gel and the metronidazole creams. However,
      the 1% metronidazole cream was significantly more irritating than petrolatum.
      CONCLUSION: There was no significant difference in the cumulative irritancy
      potential of cream and gel preparations of metronidazole. The irritancy of
      topical formulations for treating rosacea should be considered on a case by case
      basis.

PMID- 16573262
TI  - Cutaneous effects of sirolimus in renal transplant recipients.
AB  - Cancer is a major cause of death in immunosuppressed transplant patients.
      Therefore, sirolimus is frequently used in these patients for its
      immunosuppressive and antineoplastic properties. However, a variety of cutaneous
      side effects have resulted from sirolimus therapy. Consequently, dermatologists
      must be aware of such adverse events and understand the risks and benefits of
      discontinuing therapy.

PMID- 16573263
TI  - Primary cutaneous nodular amyloidosis in a patient with Sjogren's syndrome.
AB  - A 71-year-old woman with a history of Sjogren's syndrome presented for evaluation
      of a waxy nodule present on the scalp for 6 months. Histopathologic examination
      revealed deposition of homogenous eosinophilic material throughout the reticular
      dermis consistent with amyloidosis. Primary cutaneous nodular amyloidosis is a
      rare phenomenon characterized by the deposition of immunoglobin light chains by a
      clonal plasma cell population. Patients need to be monitored for progression to
      systemic amyloidosis or plasma cell dyscrasias.

PMID- 16573264
TI  - A case of an adverse reaction to topical 5-fluorouracil in irradiated skin.
AB  - A 73-year-old Caucasian male was treated in the dermatology clinic for squamous
      cell carcinoma (SCC) of the scalp by Mohs micrographic surgery. The patient
      subsequently received radiation therapy because of possible calvarium invasion.
      Approximately 2 years later, the patient developed Bowen's disease within the
      previously irradiated skin flap. The lesion was treated with topical 5
      fluorouracil (5-FU) twice daily for 4 weeks, and subsequently developed a 2 x 2
      cm full-thickness ulceration with exposed calvarium.

PMID- 16573266
TI  - Amantadine-induced livedo reticularis: a report of two cases.
AB  - In the last several years, amantadine has been increasingly prescribed for
      akinesia in Parkinson's disease and to combat fatigue associated with multiple
      sclerosis. Amantadine is a well-known medication involved in drug-induced livedo
      reticularis (LR), yet remains under-reported in the English literature. We
      describe 2 patients with amantadine livedo reticularis: one patient with multiple
      sclerosis had, previous to this eruption, tolerated 4 years of amantadine therapy
      without adverse reactions and another patient with Parkinson's disease who
      developed LR 1 month after starting amantadine.

PMID- 16573265
TI  - Serum sickness-like reaction to Pamabrom.
AB  - Pamabron is a common over-the-counter diuretic used for relief of menstrual
      associated symptoms. An urticarial eruption, with systemic complaints consistent
      with a serum sickness-like reaction, attributed to Pamabron is described. A
      review of the literature concerning Pamabron and dermatology is discussed.

PMID- 16573267
TI  - The treatment of progressive pigmented purpura with ascorbic acid and a
      bioflavonoid rutoside.
AB  - Progressive pigmented purpura (PPP) is a group of dermatoses that are benign and
      usually self-limited. However, they may persist for months or years with frequent
      recurrences. Numerous treatments have been tried, but no effective therapy has
      yet proven to be successful. This report documents the treatment of a patient
      with one subtype of PPP using ascorbic acid and a bioflavonoid rutoside given
      orally. A 42-year-old male with biopsy-proven Eczematoid-like Purpura of Doucas
      and Kapetanakis was treated with ascorbic acid 500 mg twice a day and a
      bioflavonoid rutoside 50 mg twice a day. Treatment was successful, with quick
      defervescence of the rash and no recurrence to date.

PMID- 16573268
TI  - Laser skin tightening: non-surgical alternative to the face lift.

PMID- 16573269
TI  - Exposure to TNF-alpha but not IL-1beta impairs insulin-dependent phosphorylation
      of protein kinase B and p70S6k in mouse C2C12 myogenic cells.
AB  - Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine considered to
      play an important role in muscle catabolism, but little is known about the
      mechanisms of its action. The aim of the present study was therefore to examine
      the effect of TNF-alpha pretreatment on glucose uptake and protein synthesis as
      well as the cellular content and phosphorylation of protein kinase B (PKB),
      p70S6k, Mitogen Activated Protein (MAP) kinase and p90rsk in mouse C2C12 myotubes
      stimulated with insulin. To determine whether interleukin (IL)-1beta might be
      involved in the catabolic action of TNF-alpha, the effects of IL-1beta were also
      tested. Experiments were performed on mouse C2C12 myoblasts subjected to
      differentiation in the presence of increasing concentrations of TNF-alpha (0.1
      100 ng/ml) or IL-1 (5-50 ng/ml) for 5 or 6 days. Insulin (100 nmol/l) markedly
      stimulated glucose uptake in C2C12 myotubes (202.6% of control). This effect was
      profoundly attenuated by pretreatment with TNF-alpha at a concentration of 1
      ng/ml (122.2% of control) and completely abolished by higher cytokine
      concentrations. Pretreatment of cells with TNF-alpha at a concentration of 1
      ng/ml was also effective in diminishing the effect of insulin on protein
      synthesis, whereas higher cytokine concentrations prevented hormonal stimulation
      of protein synthesis in C2C12 myotubes. Pretreatment with TNF-alpha caused a
      significant decrease in PKB protein content. Insulin-mediated activation of
      protein kinase B was significantly diminished in cells differentiated in the
      presence of TNF-alpha. Treatment of C2C12 cells with insulin led to the gel
      mobility retardation of p70S6k indicating its phosphorylation and activation. In
      cells differentiated in the presence of TNF-alpha an approximately 2-fold
      decrease of insulin-mediated p70S6k phosphorylation was noted. Six-day
      differentiation of myogenic cells in the presence of TNF-alpha did not affect the
      protein content of p42MAPK, p44MAPK, p90rsk and phosphorylation of p42MAPK.
      Neither glucose uptake nor protein synthesis stimulated by insulin were affected
      significantly by pretreatment with IL-beta. Preincubation of myogenic cells with
      IL-1beta did not modify either the protein content of PKB and p70S6k or the
      insulin-stimulated phosphorylation of these kinases. IN CONCLUSION: i) high
      concentrations of TNF-alpha, but not IL-beta, present in the extracellular
      environment during myoblast differentiation prevent the stimulatory action of
      insulin on glucose uptake and protein synthesis; ii) insulin resistance induced
      by TNF-alpha in C2C12 myogenic cells could be associated with the decreased
      insulin-mediated phosphorylation of PKB and p70s6k, but not with the basal
      phosphorylation of p42MAPK.

PMID- 16573270
TI  - The effect of increased ozone concentrations in the air on selected aspects of
      rat reproduction.
AB  - Five-month-old male rates were exposed to 0.5 ppm ozone for 50 days, 5 hours a
      day. A week before the completion of ozone exposure, a biological test was
      performed to determine the fertilization rate and the survival rate of newborns
      in both ozone-exposed and control animals. After 50 days, the rats were
      sacrificed with an overdose of halotane, and testes were collected to assess the
      morphology and motility of spermatozoa. Neither the morphology of spermatozoa nor
      motility parameters determined by the CASA (computer-assisted sperm analysis)
      system showed statistically significant differences between ozone-exposed and
      control males. The number of successful matings and the survival rate of newborns
      per litter within one year postpartum were also similar in both groups. However,
      sperm concentration was by 17% lower in ozone-exposed rats, compared with the
      control animals.

PMID- 16573271
TI  - The diagnosis of gastritis and helicobacter-like organisms infection in
      endoscopic biopsies of the canine gastric mucosa.
AB  - The aim of this study was to evaluate the prevalence of gastric Helicobacter-like
      organisms (GHLO) and gastritis in the gastric mucosa of dogs with gastric
      disorders. Tissue samples of the gastric mucosa were obtained from 30 dogs with
      gastrointestinal symptoms (vomiting, abdominal pain or discomfort, loss of
      appetite) during endoscopy. Histopathological examinations were performed and
      occurrence of GHLO infection, gastritis and other mucosal changes were estimated.
      The GHLO infection and gastritis were identified in 63.3 and 36.6% of dogs
      respectively; other mucosal changes included fibrosis in the lamina propria,
      degenerative changes of the gastric glands and hyperplasia of the parietal cells.
      The present study has revealed that microscopically found gastritis is not
      frequent in dogs examined by endoscopy. GHLO infection can be responsible for
      some cases of gastritis and hyperplasia of parietal cells in dogs.

PMID- 16573272
TI  - The effect of dimethoate and pyrantel on vitamin C concentration in the rat
      liver.
AB  - The aim of this study was to determine the content of vitamin C in the liver of
      rats exposed to dimethoate or pyrantel embonate as well as co-intoxication with
      both agents. Investigations were carried out in two stages. At each stage, the
      rats were divided into three experimental groups (I-III) and a control (C) group.
      In the first stage, rats from group I were administered pyrantel embonate at a
      two-week interval at a dose of 1/2 LD50, while the animals from group II received
      dimethoate for 28 days at a dose of 1/25 LD50, and those from group III - both
      mentioned compounds in an identical manner as in groups I and II. In the second
      stage, the rats from group I received pyrantel embonate at a dose of 1/5 LD50 for
      3 consecutive days, while the animals from group II received dimethoate at a dose
      of 1/10 LD50 for 5 consecutive days, and those from III received both compounds,
      but pyrantel was administered on day 3, 4 and 5 of dimethoate administration. The
      concentration of vitamin C after pyrantel embonate and dimethoate administration
      was influenced not only by doses of the compounds used but also by the manner of
      their application (single or co-administration). Dimethoate delivered at a dose
      of 1/25 LD50 evoked an increase in vitamin C concentration that was observed to
      continue up to the 14th day after the exposure, whereas when applied at a dose of
      1/10 LD50 it increased the vitamin C level only at the 3rd hour. A considerable
      decrease in the vitamin C level was reported after pyrantel treatment at a dose
      of 1/5 LD50. In rats from groups where the compounds were co-administered,
      increased level of vitamin C was observed at both stages of the experiment only
      in the first period after intoxication, i.e. up to the 6th hour.

PMID- 16573273
TI  - Contents of selected heavy metals in the liver, kidneys and abdominal muscle of
      the brown hare (Lepus europaeus Pallas, 1778) in Central Pomerania, Poland.
AB  - The content of iron, zinc, copper, manganese, lead, and cadmium was determined in
      the kidney, liver, and abdominal muscle of the brown hare (Lepus europaeus), a
      species known for its bioindicative potential in environmental quality
      assessment. The animals assayed were divided into immature (in their first year
      of life; n=25) and adult (n=39). The hares were acquired in an area situated far
      away from major cities and direct impacts of industrial and transport pollution.
      The zinc content found in the assayed hare's muscles (25.9 microg/g w.w.) and
      that of manganese in the kidneys, liver, and muscles (2, 2.51 i 0.85 microg/g
      w.w., respectively) tended to be higher than those reported from the brown hare
      elsewhere in Europe. The content of cadmium (particularly in the kidneys) and
      lead proved substantial and close to those typical of the hare inhabiting
      industry-affected areas. Analysis of the data pooled for all the individuals
      showed Zn and Cd contents to increase with age in the kidneys, the liver Cd
      content increasing with age as well; on the other hand, the age-Cu content was
      negative. In addition, a number of significant correlations between the metals
      themselves were revealed, particularly with respect to Zn-Cd correlation in
      kidneys (r(s)=0.47), Fe-Cd, Zn-Cu, Mn-Zn, Mn-Cu, and Mn-Pb in the liver (r(s) of
      0.42, 0.86, 0.72, 0.79, and 0.42, respectively), and Zn-Cu in the muscle
      (r(s)=0.56). The kidney cadmium content was higher by 81% in the adult than in
      the immature hare, the adult hare muscle copper content being lower by 15.5%.

PMID- 16573274
TI  - Residues of dimethoate in the liver and AchE activity in blood of rats after
      exposure to dimethoate, and dimethoate and pyrantel embonate.
AB  - The study was aimed at determining the dimethoate residues in the liver and
      acetylcholinesterase (AChE) activity in blood of rats exposed to dimethoate
      (individual intoxication), and dimethoate and pyrantel embonate (simultaneous
      intoxication). The experiment was carried out in two stages where various doses
      of preparations and exposure manners were used. In the first stage of the
      experiment, dimethoate (1/25 LD50) was administered to animals per os for 28
      days, and pyrantel embonate (1/2 LD550) twice, i.e. on the day 14th and 28th. In
      the second stage, dimethoate was administered for 5 days (1/10 LD50), and
      pyrantel embonate (1/5 LD50) on day 3, 4 and 5 from the beginning of dimethoate
      intoxication. The short presence of the dimethoate residues in the liver of the
      animals examined was found until the 2nd day after 28-day intoxication (1/25
      LD50) and until 14th day after 5-day intoxication (1/10 LD50), however, a
      distinct decrease in this insecticide residues in the liver of (analysed groups
      of) rats occurred between the 3rd hour and the 2nd day after exposure. Dimethoate
      in both applied doses significantly reduced AChE activity in blood. After
      application of the higher dose, the inhibition of AChE was more pronounced, and
      the return of its activity to physiological values lasted considerably longer. Co
      administration of pyrantel embonate and dimethoate, slightly influenced changes
      of the parameters analysed, which have been dependent not only on a dose and
      manner of pyrantel application but also on time which lapsed from exposure.

PMID- 16573275
TI  - Influence of garlic, synthetic 1,2,4-triasole derivative and herbal preparation
      echinovit C on selected indices of turkey-hens non-specific immunity.
AB  - Successful results of earlier studies on testing the immune-modulating and anti
      microbial properties of 1,2,4-triasole derivative as well as benefitial
      application of natural bio-stimulators in animal's prophylaxis and treatment
      inspired us to undertake further investigations. The aim of the present study was
      to evaluate and compare the prophylaxis effects of two natural immune-modulating
      agents, garlic (Allium sativum) extract and Echinovit C preparation and synthetic
      derivative of 1,2,4-triasole on non-specific immunity indices in slaughter turkey
      hens. The results obtained suggest that the strongest stimulatory effect is
      exerted by garlic followed by 1,2,4-triasole derivative and Echinacea juice.
      Immune-modulating action of the substances applied was manifested by an increase
      in cellular immune parameters: the percentage of phagocyting cells, NBT-positive
      granulocytes and lysozyme level.

PMID- 16573276
TI  - Immunohistochemical identification method of tumour cells in the S phase of
      mitotic cycle and its usefulness in diagnostics of mammary gland adenocarcinomas
      in bitches.
AB  - The studies aimed at identification of neoplastic cells at the S phase of mitotic
      cycle in mammary gland adenocarcinomas of bitches. The material was sampled from
      bitches of various races, aging 6 to 12 years, in which the mammary gland tumours
      developed spontaneously. The tumours were verified histopathologically and, then,
      immunohistochemical reactions were performed in order to detect cells which had
      incorporated BrdU (bromodeoxyuridine), contained Ki-67 or PCNA antigen. The
      histological preparations were photographed and obtained pictures were subjected
      to computer-assisted image analysis using Axiophot microscope (Carl Zeiss)
      coupled to a computer and the Multi-ScaneBase V 8.08 software, working under
      Windows. Fifty percent of sections from mammary gland adenocarcinomas
      demonstrated BrdU labelling index of 4-5%, 40% of 1-3%, while in the remaining
      10% of examined tumours no BrdU incorporation could be demonstrated. No evident
      relationship could be detected between the presence of BrdU incorporation and Ki
      67 or PCNA antigen presence but a significant correlation was demonstrated
      between the expression of Ki-67 and PCNA.

PMID- 16573277
TI  - Immunobiology of bovine mammary gland: apoptosis of somatic cells in milk during
      naturally occurring mastitis.
AB  - Mastitis remains a major cause of economic losses in dairy herds. It is believed,
      that the enhancement of natural defense mechanisms in mammary gland may be
      helpful in the treatment of bovine mastitis. Our study was designed to assess the
      apoptosis of leukocytes isolated from bovine milk during subclinical
      staphylococcal mastitis. Milk samples were collected from cows naturally infected
      with one pathogen--Staphylococcus aureus and from animals with mastitis caused by
      several pathogens, including S. aureus. It has been determined that the rate of
      apoptosis was lower in mastitic milk, as compared with control samples, although
      varied significantly between groups. High percentage of apoptotic cells was
      detected in milk with high counts of pathogenic bacteria. In all groups the rate
      of apoptosis was dependent on the bacterial load, although various correlations
      were identified. Thus, it is postulated, that the rate of apoptosis of somatic
      cells in mastitic milk is related to the etiology of infection and is determined
      by the bacterial load.

PMID- 16573278
TI  - Comparison of the blood plasma catecholamines level in thoroughbred and Arabian
      horses during the same-intensity exercise.
AB  - The aim of this study was to compare changes in epinephrine (E), norepinephrine
      (NE) and dopamine (DA) levels in blood plasma of two racehorses breeds: Arabian
      and Thoroughbred during moderate intensity exercise performed in the same
      conditions. The increase in plasma E level just after exercise was higher in
      Thoroughbreds than in Arabians. During the whole test, the Arabians showed the
      higher levels of NE and DA as compared to those found in Thoroughbreds.

PMID- 16573279
TI  - Evaluation of efficacy and safety of Aujeszky's disease vaccines.
AB  - Since Aujeszky's disease have become an economic problem in pig farms in late
      1960's and early 1970's many different vaccines, either inactivated or live -
      attenuated were developed. Soon it became evident that they differ in their
      efficacy. In this article a panel of tests used for evaluation of safety and
      efficacy of inactivated as well as live Aujeszky's disease vaccines is described.

PMID- 16573280
TI  - Immune response in farm animals infected or immunised with bacteria of Chlamydia
      sp. and Chlamydophila sp. genus.
AB  - Bacteria from genera Chlamydia (Ch.) and Chlamydophila (Chl.) are very pathogenic
      and may infect humans and animals. They also may cause latent infection,
      especially in animals. In this paper we discuss the non-specific and specific
      cellular and humoral immunity in farm animals, after infection or immunisation
      with Chlamydia sp. and Chlamydophila sp. bacteria. It has been shown, that the
      infection or immunisation with the microorganisms influenced the activity of
      polimorphonuclear cells (PMN) and mononuclear cells (MN) in the process of
      phagocytosis. It has also been shown that the bacteria influenced the amount and
      activity of lysozyme, activities of myeloperoxidase and lysosomal enzymes.
      Infection or immunisation with the microorganisms was demonstrated to affect
      numbers of lymphocytes T and B and those of their subpopulation as well as the
      activity of cytokines and levels of serum and secreted immunoglobulins. The
      changes were detected just a few hours after infection or immunisation and
      persisted for a few days to a few decades.

PMID- 16573281
TI  - Market power for the NHIN.

PMID- 16573282
TI  - Fraud control: New tools, new potential.

PMID- 16573283
TI  - A call to action for HIM professionals.

PMID- 16573284
TI  - Fighting fraud automatically.

PMID- 16573285
TI  - Following the digital trail.

PMID- 16573286
TI  - Benchmarking RCM.

PMID- 16573287
TI  - Helping consumers manage their PHRs.

PMID- 16573288
TI  - Structured or unstructured?

PMID- 16573289
TI  - Consumer empowerment.

PMID- 16573290
TI  - Using the SSN as a patient identifier.

PMID- 16573291
TI  - Assigning secondary codes from the history and physical.

PMID- 16573293
TI  - Compliance officer brings HIM insights to data standards work.

PMID- 16573292
TI  - Dangerous E/M coding practices. Identifying and remedying common sources of
      error.

PMID- 16573294
TI  - Health equality: the new civil rights frontier.

PMID- 16573295
TI  - Atrial fibrillation among African Americans, Hispanics and Caucasians: clinical
      features and outcomes from the AFFIRM trial.
AB  - The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM)
      study concluded that rate control with anticoagulation was equivalent overall to
      rhythm control with cardioversion for long-term survival and that anticoagulation
      reduced the risk of stroke. We compared baseline and follow-up data for three
      ethnic groups: Caucasians (n=3,599), African Americans (n=265) and Hispanics
      (n=132). Caucasians were older and more likely male, African Americans were more
      likely female and hypertensive, and Hispanics had higher prevalence of
      cardiomyopathy. Survival was better for rate control than rhythm control in
      Caucasians, equivalent in African Americans and better for rhythm control in
      Hispanics. Outcomes may be influenced by differential baseline characteristics,
      but low numbers of African Americans and Hispanics warrant caution in data
      interpretation. BACKGROUND: The AFFIRM study compared a rate-control strategy to
      a rhythm-control strategy for the treatment of atrial fibrillation (AF) in
      patients at high risk for stroke or death. It concluded that the rhythm-control
      strategy offered no survival advantage, and it also confirmed the value of
      anticoagulation to prevent complications of AF. Data have not previously been
      available for specific racial ethnic populations. METHODS: We compared baseline
      and follow-up data for the patients randomized to rate-control versus rhythm
      control in three population groups-Caucasian, African-American and Hispanic.
      RESULTS: Among 4,060 total patients, 3,599 were Caucasian, 265 were African
      American and 132 were Hispanic. At baseline, Caucasians were older and had a
      higher percentage of males, normal ejection fractions, AF as their only cardiac
      diagnosis, a prior antiarrhythmic drug failure and less congestive heart failure.
      African Americans were more likely to be female, had more hypertension and
      qualified for the study with a first episode of AF, compared to Caucasians.
      Hispanics had more cardiomyopathy at baseline than Caucasians. Overall survival
      in Caucasians at five years for the rate-control and rhythm-control groups was
      78.9% vs. 76.4%, respectively (p=0.04); for African Americans, 79.0% vs. 69.4%
      (p=0.22); and for Hispanics, 66.5% vs. 83.9% (p=0.01). Overall, survival was not
      different between the three populations. However, lower rates of event-free
      survival were recorded for Hispanics and for African Americans (p=0.0182).
      CONCLUSIONS: Different survival rates were found for rate-control versus rhythm
      control in African-American and Hispanic patients, compared to Caucasian. These
      findings may be influenced by differences in baseline characteristics, but must
      be interpreted with caution because of the small sample sizes for African
      American and Hispanic participants.

PMID- 16573296
TI  - Antenatal modes of surfactant administration for RDS prevention: a review.
AB  - OBJECTIVE: To review the body of international literature regarding lung
      surfactant supplements in order to determine: 1) the current knowledge of the
      antenatal routes of administration of surfactant supplements; 2) in-utero,
      antenatal, endotracheal surfactant treatment; 3) if antenatal, intraamniotic or
      oral administration of surfactant supplements has an equal therapeutic effect in
      the prevention of respiratory distress syndrome as endotracheal, postnatal
      administration. STUDY DESIGN: The appropriate medical subject heading terms were
      selected and applied in a search of the Medline and ACOG online databases.
      Articles focusing on fetal breathing, the fetal swallowing mechanism of amniotic
      fluid and the route of supplementary surfactant administration in both animal and
      human studies were reviewed. RESULTS: This review determined that an antenatal
      approach to supplementary surfactant administration has been attempted in both
      animal and human studies. Recent endeavors included attempts at antenatal routes
      of administration involving delivery into the mouth of the fetus or into the
      intraamniotic fluid around the mouth or nostrils. The therapeutic effect has
      proven inconclusive in its benefits. CONCLUSION: In-utero, oral delivery of
      surfactant supplements has been documented; however, the mechanism of absorption
      from the gastrointestinal tract by the lung tissue is difficult to determine, and
      the level of postnatal surfactant in the endotracheal fluid was not assessed. In
      utero, intraamniotic surfactant installation was noted in the literature;
      however, the level of surfactant in endotracheal fluid was also not documented
      postnatally. No study or technique presented a description or model for
      antenatal, endotracheal surfactant supplement administration.

PMID- 16573297
TI  - Do adverse histopathologic findings in colorectal cancer patients explain
      disparate outcomes?
AB  - We have previously reported reduced overall and disease-free survival in black
      patients from a 10-year retrospective review of 668 patients from tumor registry
      data. This study of 213 patients reports the analysis of available archived
      tissue from a city hospital (n=44 patients, 53% black) and from a university
      medical center (n=169, 10.6% black). Two senior pathologists independently
      reviewed slides for predetermined histologic criteria reported to correlate with
      survival: tumor type, stage at diagnosis, character of invasion, vascular or
      perineural invasion, the presence of residual adenoma, the presence of a Crohn's
      like reaction and number of nodes resected. Differences in discrete variables
      were compared using the Chi-squared test. Differences in continuous variables
      were analyzed using independent t tests. No statistically significant differences
      were identified in tumor stage or type by institution or race. In patients
      treated at the city hospital, there was a higher incidence of infiltrating tumors
      (85% vs. 61%, p<0.001), vascular invasion (70% vs. 36%, p<0.05) and residual
      adenoma (84% vs. 39%, p<0.05); however, no differences by race were identified.
      Blacks at both hospitals had significantly more perineural invasion (81% vs. 30%,
      p<0.05) and Crohn's-like reaction (64% vs. 30%, p<0.05) when compared to white
      patients, although there was no difference between hospitals. The total number of
      lymph nodes resected was higher at the university hospital (17.0 vs. 8.9,
      p<0.001). There were no differences in number of nodes resected at either
      institution by race. Histopathologic findings did not explain the apparent
      disparity in survival. The differences in number of nodes harvested may suggest
      inadequate resection or insufficient recovery of nodes by the pathologist.

PMID- 16573298
TI  - Low cobalamin levels in African Americans with and without sickle cell disease.
AB  - About 7% of the adult population has subclinical cobalamin (B12) deficiency.
      Subjects with sickle cell disease (SCD) may be at higher risk of cobalamin
      deficiency because of increased demand, inadequate supply, coexisting folate
      deficiency or malabsorption. We compared the clinical and laboratory
      characteristics of low serum cobalamin levels in patients with SCD with those
      patients without this hemoglobinopathy (non-SCD). Between 1993 and 2003, 105 SCD
      patients and 112 non-SCD patients who had serum cobalamin measurements were
      identified at our institution. The mean cobalamin level in SCD patients was
      significantly lower (496 +/- 352 pg/ml) than that in patients without SCD (869 +/
      660 pg/ml, p<0.0001). The frequency of low cobalamin levels, defined by a serum
      cobalamin level of <200 pg/ml, was 18.1% (19/105) and 9.8% (11/112) in SCD and
      non-SCD patients, respectively (chi2=3.11, nonsignificant). The mean age of the
      low-cobalamin SCD and non-SCD patients was 28.1 and 62.9, respectively, and their
      male:female ratios were 11:8 in SCD patients and 2:9 in non-SCD patients. None of
      the SCD patients had neurological manifestations, but nine of the 11 non-SCD low
      cobalamin level patients did. The proportion of SCD patients with unexplained low
      cobalamin levels (13/19) was higher than that in non-SCD patients (4/11,
      chi2=2.92, nonsignificant) Our data suggest that cobalamin levels are lower in
      SCD patients than in subjects without SCD, and low-cobalamin SCD patients are
      younger and more likely to be males.

PMID- 16573300
TI  - Association between elevated depressive symptoms and clinical disease severity in
      African-American adults with sickle cell disease.
AB  - OBJECTIVE: The purpose of this cross-sectional study was to examine the
      association between elevated depressive symptoms and the clinical severity of
      sickle cell disease (SCD) using African-American adults with and without SCD.
      STUDY DESIGN: The population consisted of 102 African-American adults with SCD,
      diagnosed using hemoglobin electrophoresis, individually matched on age (+/-5
      years), gender and recruitment location to 103 African-American adults without
      SCD (mean age of all subjects was 35.4 years, 55.6% female). Logistic regression
      was used to examine the association between SCD clinical severity and elevated
      depressive symptoms in bivariate and multivariable analyses. RESULTS: The
      prevalence of elevated depressive symptoms as measured using the 10-item Center
      for Epidemiological Studies Depression Scale (CES-D) was 38.6% in those with SCD,
      compared to 27.5% in those without SCD; however, this difference was not
      statistically significant (p>0.05). Compared to African Americans without SCD,
      African Americans with SCD were less educated, had lower incomes, and were more
      likely to be unemployed or disabled (p<0.01). The odds of having elevated
      depressive symptoms were 1.78 (CI: 0.94, 3.38) for those with high clinical SCD
      severity compared to those without SCD in bivariate analysis and 1.37 (CI: 0.62,
      3.02) in multivariable analysis after adjusting for socioeconomic factors.
      CONCLUSIONS: The reported relationship between elevated depressive symptoms and
      SCD may be a result of the adverse economic conditions associated with SCD.

PMID- 16573299
TI  - Lower vitamin-D production from solar ultraviolet-B irradiance may explain some
      differences in cancer survival rates.
AB  - Black Americans diagnosed with cancer generally have lower survival rates than
      white Americans, even after adjustment for stage of cancer at time of discovery
      and level of treatment received. The hypothesis developed in this work is that
      these lower cancer survival rates may be due to lower serum 25-hydroxyvitamin D
      [25(OH)DI for black Americans attributed to lower production rates of vitamin D
      from solar ultraviolet-B (UVB) irradiance due to darker skin. Black Americans
      generally have 50-75% as much serum 25(OH)D as white Americans, and vitamin D is
      now thought to reduce the risk of incidence and mortality for 18 types of cancer.
      To explore this hypothesis, data for mortality rates for various types of cancer
      for the period 1970-1994 for black Americans were used with indices for solar UVB
      levels for July, smoking, alcohol consumption, urban residence and poverty level,
      all averaged by state, in multiple linear regression analyses using the ecologic
      approach. Solar UVB was found significantly inversely correlated with mortality
      rates for breast, colon, esophageal, gastric and rectal cancers for black
      Americans, albeit with lower associations than for white Americans. Smoking and
      alcohol consumption were also significantly correlated with several cancers.
      Based on these results, it seems worthwhile to conduct observational, prevention
      and intervention studies to further test the hypothesis that vitamin D can reduce
      the risk of cancer incidence and death.

PMID- 16573301
TI  - Racial differences in beliefs about genetic screening among patients at inner
      city neighborhood health centers.
AB  - BACKGROUND: Genetic testing has the potential to identify persons at high risk
      for disease. Given the history of racial disparities in screening, early
      detection and accessing treatment, understanding racial differences in beliefs
      about genetics is essential to preventing disparities in some conditions.
      METHODS: In 2004, a sample of older adult patients from four inner-city health
      centers was surveyed to assess beliefs about genetic determinants of disease,
      genetic testing and religion. Logistic regression determined which beliefs were
      associated with race. RESULTS: Of the 314 respondents, 50% were African
      Americans. Most respondents thought that sickle cell disease, cystic fibrosis and
      diabetes are primarily genetic. African Americans were more likely than
      Caucasians to believe that genetic testing will lead to racial discrimination
      (Odds ratio (OR): 3.02, 95% confidence interval (CI): 1.5-6.0) and to think that
      all pregnant women should have genetic tests (OR=3.8, 95% CI: 1.7-8.6). African
      Americans were more likely to believe that God's Word is the most important
      source for moral decisions (OR: 3.6, 95% CI :1.5-8.7). CONCLUSION: African
      Americans and Caucasians differ in beliefs about genetic testing and the basis
      for moral decision-making. Acknowledging and understanding these differences may
      lead to better medical care.

PMID- 16573302
TI  - Toward a conceptual reexamination of the patient-physician relationship in the
      healthcare institution for the new millennium.
AB  - There is a crisis in the patient-physician relationship. Mass media, managed care
      and malpractice are just a few factors that contribute to a lack of trust,
      understanding and loyalty in the patient-physician relationship. We have
      experienced some select concepts within the Society, Culture and Personality
      (SCP) model. In it, we explore how social class, age, race, ethnicity and family
      background of the patient impact upon the patient-physician relationships. The
      analysis of the sick role is most prominent, and in this interactive process
      empathy must be given to each person who seeks medical help.

PMID- 16573303
TI  - Racism and health inequity among Americans.
AB  - Research reports often cite socioeconomic status as an underlying factor in the
      pervasive disparities in health observed for racial/ethnic minority populations.
      However, often little information or consideration is given to the social history
      and prevailing social climate that is responsible for racial/ethnic socioeconomic
      disparities, namely, the role of racism/racial discrimination. Much of the
      epidemiologic research on health disparities has focused on the relationship
      between demographic/clinical characteristics and health outcomes in main-effects
      multivariate models. This approach, however, does not examine the relationship
      between covariate levels and the processes that create them. It is important to
      understand the synergistic nature of these relationships to fully understand the
      impact they have on health status. PURPOSE: A review of the literature was
      conducted on the role that discrimination in education, housing, employment, the
      judicial system and the healthcare system plays in the origination, maintenance
      and perpetuation of racial/ethnic health disparities to serve as background
      information for funding Program Announcement, PA-05-006, The Effect of Racial/
      Ethnic Discrimination/Bias on Healthcare Delivery (http:// grants.nih.gov/grants/
      guide/pa-files/PA-05-006.html). The effect of targeted marketing of harmful
      products and environmental justice are also discussed as they relate to
      racial/ethnic disparities in health. CONCLUSION: Racial/ethnic disparities in
      health are the result of a combination of social factors that influence exposure
      to risk factors, health behavior and access to and receipt of appropriate care.
      Addressing these disparities will require a system that promotes equity and
      mandates accountability both in the social environment and within health delivery
      systems.

PMID- 16573304
TI  - Platelet parameters in women with iron deficiency anemia.
AB  - BACKGROUND: In iron deficiency anemia (IDA), several changes in platelets have
      been reported. Therefore, a relationship between iron metabolism and
      thrombopoiesis should be considered. The aim of this study was to evaluate the
      platelet parameters in women with IDA. MATERIALS AND METHODS: Eighty-six women of
      mean age 37 +/- 13 (16-70) years with IDA were enrolled this study. The
      relationship between serum iron parameters (such as iron, iron-binding capacity,
      iron saturation and ferritin) and platelet parameters (such as platelet counts,
      platelet crit, mean platelet volume and platelet distribution width) were
      evaluated by using Pearson correlation and stepwise logistic regression tests.
      RESULTS: Thrombocytosis and thrombocytopenia were noted in 24 (27.9%) and two
      (2.3%) patients, respectively. Platelet counts were increased when serum iron,
      iron saturation, ferritin and mean platelet volume were decreased in this study.
      There was a linear relationship between platelet counts and platelet crit
      (p<0.001) but inverse relationships between platelet counts and both mean
      platelet volume and iron saturation (p<0.001, for both). Also there were a linear
      relationship between platelet distribution width and mean platelet volume
      (p<0.001) and an inverse correlation between platelet distribution width and mean
      corpuscular volume (p<0.001). We did not find any correlation between platelet
      crit and studied iron parameters (p>0.05). CONCLUSIONS: In IDA, the most
      important factor affecting platelet counts was iron saturation. These changes in
      the platelet parameters may be related to low levels of tissue iron. This study
      suggested that decreased iron saturation might stimulate megakaryopoiesis.
      Moreover, iron may have an inhibitor effect on platelet counts.

PMID- 16573305
TI  - Assessing barriers to the identification of elder abuse and neglect: a
      communitywide survey of primary care physicians.
AB  - Elder abuse and neglect represents an extensive medical and social problem in the
      United States with an estimated prevalence of 4-10% of older persons. Physicians
      are mandated to report suspected abuse, but <2% of Adult Protective Service
      reports are filed by physicians. A knowledge or attitude survey was mailed to all
      adult primary care physicians in the study community. The intent was to explore
      possible knowledge deficits and perceived barriers to physician reporting.
      Regarding the attitude measure, physicians expressed that a lack of understanding
      of reporting mechanisms represented the most significant obstacle. Regarding the
      knowledge measure, a majority of the responding physicians were unable to
      recognize key risk factors for abuse. Study findings will be used to develop
      local educational programs to enhance physician understanding of elder abuse.

PMID- 16573306
TI  - A simple stratification & storage system for samples and supplies.
AB  - Expiration dates on drug samples are often cumbersome to check due to their poor
      legibility and variable location on the containers. Consequently, many samples
      remain unused past their expiration dates and must be discarded. Timely use of
      samples can be facilitated by legibly writing their expiration dates on the top
      surface of their containers, stratifying all samples by their expiration dates in
      chronologically labeled shelves and reviewing the stock monthly. This procedure
      should also be useful for other dated items.

PMID- 16573307
TI  - Female genital mutilation: knowledge, attitude and practice among nurses.
AB  - BACKGROUND: Female genital mutilation (FGM) and cutting is a subject of global
      interest, with many countries of the world still practicing it despite efforts by
      the WHO and other agencies to discourage the practice. The highest known
      prevalence is in Africa. OBJECTIVES: To determine the knowledge, attitude and
      practice of FGM among nurses in the ancient metropolis of Benin in a Nigerian
      state where FGM is illegal. RESULTS: One-hundred-ninety-three nurses in the study
      hospital were recruited in the study out of which 182 (94.3%) appropriately
      filled and returned the questionnaires. The average age of respondents was 37
      years, and the average duration of postgraduation experience was 14.5 years. Most
      respondents are of Bini (36.8%) and Esan (34.1%) ethnic origin. All respondents
      identified at least one form of FGM, but only 12 respondents (6.6%) could
      correctly identify the four types of FGM. The harmful effects of FGM identified
      by the majority of respondents include hemorrhage, difficult labor/childbirth,
      genital tears, infections and scar/keloid formation. Forty-four (24.2%) of
      respondents were of the opinion that some forms of FGM are harmless. Eighty
      nurses admitted to having undergone FGM, for a prevalence of 44%. Five
      respondents (2.8%) view FGM as a good practice and will encourage the practice.
      Twelve respondents (6.6%) routinely perform FGM out of which seven (58.3%) viewed
      FGM as a bad practice. Nurses performing FGM routinely were those who had spent
      >20 years (59%) and 11-20 years (41%) in the profession. Another 26 (14.3%) had
      performed FGM before, though not on a routine basis. Of this latter group, 15
      will perform FGM in the future when faced with certain circumstances. Reasons for
      FGM practice were mainly cultural. Eight of the respondents would have their
      daughters circumcised. CONCLUSION: Nurses perceive FGM in Benin as cultural.
      Almost half have had FGM themselves, and a small percentage recommend it to their
      daughters. Discouraging FGM practice will require culturally sensitive education
      of the healthcare providers and the population at large on the ill effects of
      FGM, including the risk to health and violations of human rights.

PMID- 16573308
TI  - Primary prevention of type-2 diabetes in developing countries.
AB  - Although diabetes is now a worldwide epidemic, the rate of increase in its
      prevalence in developing countries is alarming. By the year 2025, more than three
      quarters of all persons with diabetes will reside in developing countries. India
      and China are leading this surge in diabetes, and sub-Saharan Africa is currently
      at a lower prevalence rate. However, the estimated increase is substantial among
      African descendants in the Americas, West Indies and throughout the diaspora.
      There are compelling reasons why aggressive efforts must be directed toward
      primary prevention of diabetes in developing countries. Once diabetes develops,
      the cost of caring for patients is prohibitive. Poorly managed diabetes leads to
      several complications (e.g., end-stage renal failure, blindness, amputation and
      heart disease) that many developing countries are ill equipped to tackle. In
      landmark trials, lifestyle modification approaches are more efficacious than
      expensive medications in the prevention of diabetes. This is fortunate because
      lifestyle modification can be implemented locally, whereas medications often need
      to be imported at high cost. The first task is the education of policymakers on
      the urgent need for timely action to prevent the looming epidemic of diabetes.
      Once governments become convinced of its critical value, the translation of
      diabetes prevention through dietary modification and increased physical activity
      would require careful planning, extensive piloting and creativity in the
      allocation of scant resources. External support, foreign aid, debt forgiveness
      and other forms of creative financing will almost certainly be needed to
      implement widespread diabetes prevention programs in developing countries.

PMID- 16573309
TI  - Parental substance abuse, reports of chronic pain and coping in adult patients
      with sickle cell disease.
AB  - There is increasing interest from a social learning perspective in understanding
      the role of parental factors on adult health behaviors and health outcomes. Our
      review revealed no studies, to date, that have evaluated the effects of parental
      substance abuse on reports of chronic pain and coping in adult patients with
      sickle cell disease (SCD). We explored the effects of parental substance (alcohol
      or drug) abuse on reports of the sensory, affective and summary indices of pain
      in 67 adult patients, mean age 38.9 (13.5), with SCD. We also explored the
      effects of parental substance abuse on psychopathology associated with pain and
      active coping. Twenty-four percent of patients reported that their parent(s)
      abused substances. Patients whose parent(s) were characterized as substance
      abusers reported greater sensory (p=0.02), affective (p=0.01) and summary (VAS;
      p=0.02) indices of pain as compared to their counterparts, whose parent(s) were
      not characterized as substance abusers. Patients did not differ in average age,
      education or the propensity to respond in a socially acceptable manner. There was
      a significant trend towards patients who characterized their parents as abusers
      scoring higher than their counterparts on active coping. We propose a Social
      Learning Theory to explain the current findings and suggest a need for additional
      prospective research to simultaneously explore biological (genetic) and social
      factors that influence the interpretation, experience and reporting of chronic
      pain in adult patients with chronic disease.

PMID- 16573310
TI  - National patterns of dementia treatment among elderly ambulatory patients.
AB  - PURPOSES: To assess patterns of dementia/Alzheimer's disease (AD) management and
      to investigate predictive factors of cholinesterase inhibitor prescriptions.
      METHODOLOGY: A cross-sectional study was conducted using a national survey among
      the elderly aged >60 from 2000 to 2002. Visit characteristics and cholinesterase
      inhibitor prescriptions associated with dementia/AD status were evaluated. MAIN
      FINDINGS: A total of 25,561 visit records were identified. Of the total visits,
      only 0.6% had dementia/AD records. Most of the dementia/AD visits were made by
      women (60.6%) and white patients (93.5%). Of the dementia/AD visits, about half
      (46.5%) were prescribed with one or more cholinesterase inhibitors. Donepezil was
      the most prevalent agent (68.0%) followed by rivastigmine (26.0%). Logistic
      regression analyses indicated that the physician's specialty was a strong
      predictor for cholinesterase inhibitor prescription; psychiatrists [odds ratio
      (OR)=5.5; p<0.01] and neurologists (OR=2.6; p<0.03) were more likely to prescribe
      cholinesterase inhibitor than other physicians. Other characteristics including
      race did not show significant association. CONCLUSIONS: The study findings
      suggest that physicians who specialized in psychiatry and neurology predominantly
      provided ambulatory care services for dementia patients. More efforts should be
      given to detect and to treat dementia patients with cognitive-enhancing agents
      after the formal diagnosis in the ambulatory care setting.

PMID- 16573311
TI  - Duloxetine in the treatment of major depressive disorder: comparisons of safety
      and efficacy.
AB  - BACKGROUND: Pooled data from double-blind, placebo-controlled studies were
      utilized to compare the safety and efficacy of duloxetine in the treatment of
      major depressive disorder (MDD) in African-American and Caucasian patients.
      METHODS: Efficacy and safety data were pooled from seven double-blind, placebo
      controlled clinical trials of duloxetine. Patients (aged > or =18 years) meeting
      DSM-IV criteria for MDD received duloxetine (40-120 mg/day; African Americans,
      N=69; Caucasians, N=748) or placebo (African Americans, N=59; Caucasians, N=594)
      for up to nine weeks. Efficacy measures included the 17-item Hamilton Rating
      Scale for Depression (HAMD17) total score, the Clinical Global Impression of
      Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and
      Visual Analog Scales (VAS) for pain. Safety was assessed using discontinuation
      rates, spontaneously reported treatment-emergent adverse events, vital signs and
      laboratory analyses, RESULTS: Based upon mean changes in HAMD17, CGI-S and PGI-I
      scales, the magnitude of duloxetine's treatment effects did not differ
      significantly between African-American and Caucasian patients. Discontinuation
      rates due to adverse events among duloxetine-treated patients were 13.0% for
      African Americans and 17.0% for Caucasians. No adverse event led to
      discontinuation in more than one African-American patient. The most common
      treatment-emergent adverse events in both ethnic groups included nausea,
      headache, constipation, dizziness and insomnia. The rate of occurrence of these
      events did not differ significantly between African-American and Caucasian
      patients. Mean changes from baseline for pulse, blood pressure, weight and
      laboratory analytes were small and showed no significant differences between
      African-American and Caucasian patients. CONCLUSION: In this analysis of data
      from seven clinical trials, no convincing evidence was found to suggest that the
      overall safety and tolerability profile or the efficacy profile for duloxetine in
      this cohort of African-American patients differed from that observed in a
      comparator group of Caucasian patients. The results from these analyses provide
      supportive evidence for the efficacy and safety of duloxetine in the treatment of
      MDD in African-American patients.

PMID- 16573312
TI  - Hamilton Naki, transplant surgeon.
AB  - A biographic sketch of Hamilton Naki is presented here. He was a great self
      taught surgeon whose contributions to the world of transplantation were largely
      ignored due to the apartheid system of South Africa. He assisted Christian
      Barnard in the first human heart transplant in 1967.

PMID- 16573313
TI  - Intercostal nerves block for mastectomy in two patients with advanced breast
      malignancy.
AB  - Regional anesthesia is recognized as an alternative to general anesthesia for
      modern breast cancer surgery. Various techniques of block have been described.
      Each has its unique problems. Regional anesthesia was chosen for simple
      mastectomy in two patients with advanced breast malignancy, due to compromised
      pulmonary status resulting from widespread malignant infiltration of both lungs.
      We used intercostal nerves block. The block was supplemented with an
      infraclavicular infiltration to interrupt the branches of the superficial
      cervical plexus that provide sensation to the upper chest wall and subcutaneous
      infiltration in the midline to block the nerve supply from the contralateral
      side. Anesthesia was generally effective and the operations were uneventful. Both
      patients and surgeons expressed satisfaction. We conclude that where patients
      have significant comorbidities that make general anesthesia undesirable, the use
      of intercostal nerves block remains a safe and reliable anesthetic option that
      allows the patient access to surgery for simple mastectomy.

PMID- 16573314
TI  - Inadvertent lumbosacral plexopathy due to temporary pacemaker implantation.
AB  - Reported here is a 70-year-old man who suffered from a lumbosacral plexopathy
      after a temporary pacemaker implantation. Drawing attention to the increased
      number of femoral catheterizations in cardiovascular practice, we have
      highlighted some neuromuscular complications pertaining to these type of
      interventions.

PMID- 16573315
TI  - Drug-induced aseptic meningitis: a physician's challenge.

PMID- 16573316
TI  - Susceptibility of adult Aethina tumida (Coleoptera: Nitidulidae) to
      entomopathogenic fungi.
AB  - Aethina tumida Murray (Coleoptera: Nitidulidae) is an invasive parasite species
      in populations of honey bees, Apis mellifera L. Aiming toward substitution of
      chemical control, we here identified a naturally occurring fungal pathogen of
      adult A. tumida from its endemic range in South Africa [Metarhizium anisopliae
      (Metschnikoff) Sorokin variety anisopliae strain FI-203]. The susceptibility of
      adult beetles (n = 400) to this fungus and to three other generalist
      entomopathogenic fungal isolates [Metarhizium anisopliae, Beauveria bassiana
      (Balsamo) Vuillemin, and Hirsutella illustris Minter & Brady] was assessed using
      spore suspension bioassays. The data revealed significantly increased mortality
      in the B. bassiana (74.00 +/- 8.94%) and M. anisopliae variety anisopliae (28.00
      +/- 16.43%) tests but not in the H. illustris (2.00 +/- 4.47%) and M. anisopliae
      (12.00 +/- 8.37%) groups. The results indicate a potential for entomopathogenic
      fungi as an alternative control of A. tumida.

PMID- 16573317
TI  - Human factors facilitating the spread of a parasitic honey bee in South Africa.
AB  - Workers of the honey bee subspecies Apis mellifera capensis (Eschscholtz) produce
      female offspring by thelytokous parthenogenesis and can parasitize colonies of
      other subspecies. In 1990, translocation of 400 colonies of A. m. capensis into
      the distribution area of A. m. scutellata by a commercial beekeeper triggered a
      dramatic parasitic phenomenon. Parasitized colonies died within a few months of
      infestation, and this resulted in the loss of tens of thousands of colonies by
      commercial beekeepers in the A. m. scutellata range in South Africa. To deal with
      the problem and to identify methods that would limit the impact of the social
      parasite, we investigated the link between beekeeping management and severity of
      parasitic infestations in terms of colony mortality and productivity. We
      demonstrate that colonies from apiaries subjected to migrations are very
      susceptible to infestation and consequently show dramatic mortality. Their
      productivity is also inferior to sedentary colonies and those in isolated
      apiaries in terms of honey yield and brood quantity. Furthermore, by
      concentrating hives in small areas and often in the vicinity of other beekeepers,
      cross-infestations can easily occur. This can undermine previously parasite-free
      beekeeping businesses. As a result of our surveys, we propose beekeeping
      practices based on locally trapped bees, reduced migration, and better control of
      parasite spread, thus promoting the conservation of these pollinators. If
      followed by all the South African beekeepers, these measures should limit the
      spread of the parasite until it is eliminated within a few years, after which
      full migratory beekeeping practices could resume.

PMID- 16573318
TI  - Effects of long-term storage on potency of TM Biocontrol-1, the registered viral
      insecticide of Orgyia pseudotsugata (Lepidoptera: Lymantriidae).
AB  - The article presents the results of bioassaying 39 samples of TM Biocontrol-1, a
      viral insecticide, from 10 different lots and various sizes of vacuum-sealed
      packages that were stored at -10 degrees C for 5-15 yr. This is the first study
      to present potency data for a registered virus product stored for this length of
      time. Laboratory bioassays in insects from the same colony from which the TM
      Biocontrol-1 was produced showed that the stored viral insecticide is still
      effective, although it lost approximately 30% of its effectiveness during
      storage. A direct correlation of this loss with the length of time in storage is
      not apparent. Bioassays also showed that there are significant differences in the
      susceptibility of Douglas-fir tussock moth, Orgyia pseudotsugata (McDunnough),
      larvae from different geographic regions to OpMNPV (family Baculoviridae, genus
      Nucleopolyhedrovirus) infection. Package size did not affect the potency of
      stored TM Biocontrol-1. There were no clear, significant differences in the
      effectiveness among lots of TM Biocontrol-1 processed by different organizations.

PMID- 16573319
TI  - Effects of hydrophilic and hydrophobic kaolin-based particle films on pea aphid
      (Homoptera: Aphididae) and its entomopathogen Pandora neoaphidis
      (Entomophthorales: Entomophthoraceae).
AB  - Hydrophobic and hydrophilic kaolin-based particle films are effective for control
      of insect pests in certain agricultural crops. How these products interact with
      potential biological control agents is not well documented. This study was
      conducted to evaluate the effects of the hydrophobic (M96-018) and hydrophilic
      (Surround WP) kaolin-based particle films (Engelhard Corporation, Iselin, NJ) on
      pea aphid, Acyrthosiphon pisum (Harris), on peas (Pisum spp.), and on the fungal
      aphid pathogen Pandora neoaphidis (Remaudiere and Hennebert) Humber. Over two
      field seasons (2001 and 2002) in northern Idaho, applications of M96-018
      significantly reduced the rate of pea aphid increase on pea, but Surround WP,
      tested only in 2001, did not reduce aphid population growth rate. Neither
      particle film treatment was as effective as a standard application of
      esfenvalerate (DuPont Asana). In the laboratory, particle films suppressed pea
      aphid populations by up to 30%. M96-018 seemed to have some repellent activity
      based on aphid distributions after treating plants. When applied along with P.
      neoaphidis conidia, M96-018 but not Surround WP caused higher percentage of
      infection mortality of pea aphids by P. neoaphidis than occurred on controls
      treated only with P. neoaphidis conidia. P. neoaphidis conidia deposited on glass
      slides coated with M96-018, produced more germ tubes and secondary conidia than
      those deposited on untreated glass slides or slides treated with Surround WP.
      This result suggests that greater infection of pea aphids on plants treated with
      M96-018 is in part a result of a direct enhancement of fungal germination by the
      particle film.

PMID- 16573320
TI  - Irradiation as a methyl bromide alternative for postharvest control of Omphisa
      anastomosalis (Lepidoptera: Pyralidae) and Euscepes postfasciatus and Cylas
      formicarius elegantulus (Coleoptera: Curculionidae) in sweet potatoes.
AB  - Irradiation studies were conducted with three sweet potato, Ipomoea batatas (L.)
      Lam., pests to determine an effective dose for quarantine control. Dose-response
      tests indicated that the most radiotolerant stage occurring in roots was the pupa
      of sweetpotato vine borer, Omphisa anastomosalis (Guenee), and the adult of West
      Indian sweetpotato weevil, Euscepes postfasciatus (Fairmaire), and sweetpotato
      weevil, Cylas formicarius elegantulus (Summers). In large-scale confirmatory
      tests, irradiation of 60,000 C. formicarius elegantulus adults, 62,323 E.
      postfasciatus adults, and 30,282 O. anastomosalis pupae at a dose of 150 Gy
      resulted in no production of F1 adults, demonstrating that this dose is
      sufficient to provide quarantine security.

PMID- 16573321
TI  - Mode of action of a novel nonchemical method of insect control: atmospheric
      pressure plasma discharge.
AB  - Atmospheric pressure plasma discharge (APPD) has been applied to a number of
      industrial applications, including the bacterial sterilization of medical
      equipment of bacteria. APPD may also have applications in insect control. A
      positive correlation was found between exposure time to APPD and mortality of
      western flower thrips, Frankliniella occidentalis (Pergande); tobacco thrips,
      Frankliniella fusca (Hinds); Asian tiger mosquito, Aedes albopictus (Skuse);
      twospotted spider mite, Tetranychus urticae Koch; and German cockroach, Blattella
      germanica (L.), with the level of mortality also increasing with time after
      treatment. Cockroaches exposed to APPD for 60, 90, 120, and 180 s lost on average
      7.5 +/- 0.8, 8.1 +/- 0.6, 8.7 +/- 0.4, and 10.1 +/- 1.1 (+/-1 SEM) mg of water
      weight, respectively, which was an increase over that of the controls. The
      metabolic rate of cockroaches exposed to plasma for 180 s increased from 0.79 +/-
      0.03 to 1.07 +/- 0.04 ml of oxygen consumed mg-cockroach(-1) h(-1) at standard
      temperature and pressure. The level of cuticular hydrocarbons identified by
      electron impact gas chromatography-mass spectrometry were not significantly
      affected by plasma exposure in the green peach aphid, Myzus persicae (Sulzer),
      German cockroach, and citrus mealybug, Planococcus citri (Risso), except for a
      reduction in n-tritriacontane in the latter. However, changes in the behavior of
      cockroaches after plasma exposure, including the loss of photo-, vibro-, and
      thigmotropic responses, inability to right themselves, and hyperexcitatory
      symptoms, suggest that the site of action of APPD in insects is the nervous
      and/or neuromuscular system.

PMID- 16573322
TI  - Morphometric and mating compatibility of Dectes texanus texanus (Coleoptera:
      Cerambycidae) from soybean and sunflower.
AB  - The cerambycid Dectes texanus texanus LeConte that infests soybean, Glycine max
      (L.) Merr., is thought to be the same Dectes that damages sunflower, Helianthus
      annuus L. However, morphometric characteristics and mating compatibility between
      individuals from soybean and sunflower fields have not been assessed. Eight
      hundred eighty stalks of soybean and sunflower residues infested with Dectes were
      collected from Texas and Kansas. Outside stalk diameter of sunflower (22.6 mm)
      was 3.2 times greater than that of soybean. Diameters of tunnels by Dectes in
      sunflower and soybean were 7.0 and 3.4 mm, respectively. Widths of head capsules
      and pronotums were approximately 1.3 times greater for Dectes larvae from
      sunflower than soybean. Larval, pupal, and adult Dectes from sunflower were
      approximately 2.5 times heavier and 1.3 times longer than from soybean. Adults
      reared from residues of soybean and sunflower were paired to evaluate mating
      compatibility. Although individuals collected and reared from different crop
      residues differed significantly in size, percentage of mating success by Dectes
      from the two crops (26.2%) did not differ significantly from that by adults from
      the same kind of crop (34.9%). Results indicated that Dectes that infest soybean
      and sunflower are the same species and reconfirmed that farmers should not plant
      soybean and sunflower in rotation or in adjacent fields.

PMID- 16573324
TI  - Soybean plant stage and population growth of soybean aphid.
AB  - The soybean aphid, Aphis glycines Matsumura, is a newly invasive species of aphid
      in North America. Previous studies disagree as to whether soybean, Glycine max
      (L.) Merr., plant stage has an impact on aphid intrinsic rate of increase.
      Therefore, the growth rate of soybean aphids on soybean plants of different
      stages was examined at two different scales in the field. A planting date
      experiment was used to measure the population growth of soybean aphids on plants
      of different stages. Clip-cages were used to measure life history characteristics
      of individual aphids on plants of different stages. No differences were found in
      the population growth or dynamics of soybean aphids in the planting date
      experiment. The life history characteristics of individual aphids also showed no
      significant difference when feeding on different growth stages of soybean plants.
      The impact of these findings on soybean aphid management is discussed and the
      possible reasons why the results differ from previous estimates of the aphid
      growth-plant stage relationship are considered.

PMID- 16573323
TI  - Toxicity of three acaricides to Tetranychus urticae (Tetranychidae: Acari) and
      Orius insidiosus (Anthocoridae: Hemiptera).
AB  - Management for twospotted spider mite, Tetranychus urticae Koch, populations in
      peanut, Arachis hypogaea L., relies on acaricides. The outcomes of acaricide
      applications are most predictable when complete information on their toxicity and
      specificity is available. Specifically, the degrees to which acaricides impact
      different stages of T. urticae and natural enemies combined determine the overall
      efficacy of an acaricide application. The objectives of this study were to
      determine stage-specific direct and residual efficacies of three acaricides
      (fenpropathrin, etoxazole, and propargite) against T. urticae, and the direct and
      residual toxicity of the acaricides to Orius insidiosus (Say) adults. Direct
      toxicity of acaricides to T. urticae was measured on peanut cuttings. All
      acaricide treatments caused significant mortality to a mixed stage population of
      T. urticae, and mortality did not differ among the acaricides 7 d after
      treatment. When toxicity to eggs was tested, the proportion of eggs that hatched
      for all acaricide treatments was significantly lower than the control, with
      etoxazole and propargite causing 100% mortality. Exposure to acaricide residues
      caused < 30% mortality of T. urticae adults 1 and 2 d after treatment and was not
      significantly different from the control. Fenpropathrin and propargite caused
      100% mortality and etoxazole caused > 50% mortality of O. insidious adults after
      direct exposure to the acaricides. Residual toxicity of acaricides to O.
      insidiosus adults varied but remained toxic to O. insidiosus longer than to T.
      urticae. Fenpropathrin had the longest residual effect on O. insidiosus adults,
      causing > 95% mortality after 14 d; etoxazole and propargite caused < 30%
      mortality after 14 d.

PMID- 16573325
TI  - Dispersal of boll weevils (Coleoptera: Curculionidae) from cotton modules before
      ginning.
AB  - We characterized the level of risk of boll weevil, Anthonomus grandis grandis
      Boheman, reintroduction to an eradication zone posed by dispersal from cotton
      modules during and after transport to the gin. Mark-release-recapture experiments
      in August and September in Texas indicated that most weevils disperse rapidly
      from the module surface, temperature permitting, unless confined under a module
      tarp, where most died. Nevertheless, 1-5% of released weevils were recovered
      alive after 24 h on the side and top surfaces of modules, representing potential
      dispersants. Mortality of boll weevils caged on the top surface of a module was
      95-100% after 1-4 d when maximum air temperatures were > or = 33 degrees C and 72
      100% when minimum temperatures were -7 degrees C or lower, but a few survived
      even after experiencing a minimum daily temperature of -12 degrees C. Under warm
      (daily maximum temperatures > or = 25 degrees C) and cold (daily minimum
      temperatures < or = 0 degrees C) weather conditions, survival was higher under
      the tarp than on the open surface of the module (20 versus 7% and 42 versus 26%,
      respectively), but mortality was 100% in both locations when temperatures reached
      34 degrees C. Our results indicate that although the threat to an eradication
      zone posed by boll weevil dispersal from an infested module is very low under
      most environmental conditions, it is probably greatest when 1) a module is
      constructed and transported from an infested zone during weather too cool for
      flight, followed by warm weather favorable for flight at the gin yard; or 2) such
      a module is transported immediately after construction in moderate-to-warm
      weather.

PMID- 16573326
TI  - Control decision rule for European chafer (Coleoptera: Scarabaeidae) larvae in
      field corn.
AB  - After greenhouse and outdoor microplot experiments, a critical density of two
      third instars per microplot for third instars of European chafer, Rhizotrogus
      (Amphimallon) majalis (Razoumowsky), in corn, Zea mays L., was derived. On
      average, the number of missing or damaged plants increased approximately 8% from
      zero to two larvae per 900 cm2. Furthermore, 23 fields in 2 yr were sampled for
      larvae along transects by using a golf cup cutter as the sampling tool and the
      critical density of 0.2 larva per sampling unit as the critical density. The
      sampling unit was one golf cup cutter with a diameter of 10.8 cm or 91.4 cm2 (10
      sampling units approximately 900 cm2 approximately 1 foot2). Fieldwide means and
      variation were modeled to Taylor's power law, a = 1.42 and b = 1.47, and 20 of 23
      fields fit the negative binomial probability distribution. Wald's formula for a
      sequential sampling plan was most accurate and least time-consuming, according to
      the operating characteristic and the average sample number function, relative to
      Iwao's and converging lines formulae. Percentage of sand, topography, soil bulk
      density, and proximity to trees were measured as potential predictors of areas
      with high larval density. Percentage of sand and soil bulk density were
      significant predictors, and topography and proximity to trees were not
      significant predictors. Field areas where the percentage of sand is high and the
      soil bulk density is low to moderate or where the percentage of sand is moderate
      and the soil bulk density is low should be chosen as sampling locations.

PMID- 16573327
TI  - Laboratory evaluation of the toxicity of systemic insecticides for Control of
      Anoplophora glabripennis and Plectrodera scalator (Coleoptera: Cerambycidae).
AB  - Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae) is one of the
      most serious nonnative invasive forest insects discovered in North America in
      recent years. A. glabripennis is regulated by federal quarantines in the United
      States and Canada and is the subject of eradication programs that involve
      locating, cutting, and chipping all infested trees. Other control methods are
      needed to aid in eradication and to form an integrated management program in the
      event eradication fails. We conducted laboratory bioassays to determine the
      toxicity of two systemic insecticides, azadirachtin and imidacloprid, for
      potential control of A. glabripennis and the cottonwood borer, Plectrodera
      scalator (F.) (Coleoptera: Cerambycidae), a closely related native cerambycid.
      Larvae of both cerambycid species were fed artificial diet with dilutions of
      azadirachtin or imidacloprid for 14 wk. Both insecticides exhibited strong
      antifeedant effects and some toxicity against A. glabripennis and P. scalator
      larvae. For A. glabripennis, the highest larval mortality at the end of the
      bioassay was 60% for larvae fed artificial diet treated with azadirachtin (50
      ppm) or imidacloprid (1.6 ppm). For P. scalator, the highest larval mortality at
      the end of the bioassay was 100% for larvae fed artificial diet treated with
      azadirachtin (50 ppm) or imidacloprid (160 ppm). At 14 wk, the LC50 values for P.
      scalator were 1.58 and 1.78 ppm for azadirachtin and imidacloprid, respectively.
      Larvae of both species gained weight when fed diet treated with formulation
      blanks (inert ingredients) or the water control but lost weight when fed diet
      treated with increasing concentrations of either azadirachtin or imidacloprid. In
      a separate experiment, A. glabripennis adults were fed maple twigs treated with
      high and low concentrations of imidacloprid. A. glabripennis adult mortality
      reached 100% after 13 d on twigs treated with 150 ppm imidacloprid and after 20 d
      on twigs treated with 15 ppm imidacloprid. There was no visible feeding by A.
      glabripennis adults on twigs treated at the higher imidacloprid rate, and feeding
      was significantly reduced for adults placed on twigs treated at the low
      imidacloprid rate compared with adults on untreated twigs. In summary,
      imidacloprid and azadirachtin had both antifeedant and toxic effects against A.
      glabripennis and P. scalator and have potential for use in management programs.
      Based on our results, the delivery of high and sustained insecticide
      concentrations will be needed to overcome the antifeedant effects and lengthy
      lethal time for both larvae and adults exposed to these insecticides.

PMID- 16573328
TI  - Efficacy of systemic insecticides for protection of loblolly pine against
      southern pine engraver beetles (Coleoptera: Curculionidae: Scolytinae) and wood
      borers (Coleoptera: Cerambycidae).
AB  - We evaluated the efficacy of the systemic insecticides dinotefuran, emamectin
      benzoate, fipronil, and imidacloprid for preventing attacks and brood production
      of southern pine engraver beetles (Coleoptera: Curculionidae: Scolytinae) and
      wood borers (Coleoptera: Cerambycidae) on standing, stressed trees and bolt
      sections of loblolly pine, Pinus taeda L., in eastern Texas. Emamectin benzoate
      significantly reduced the colonization success of engraver beetles and associated
      wood borers in both stressed trees and pine bolt sections. Fipronil was nearly as
      effective as emamectin benzoate in reducing insect colonization of bolts 3 and 5
      mo after injection but only moderately effective 1 mo after injection. Fipronil
      also significantly reduced bark beetle-caused mortality of stressed trees.
      Imidacloprid and dinotefuran were ineffective in preventing bark beetle and wood
      borer colonization of bolts or standing, stressed trees. The injected formulation
      of emamectin benzoate was found to cause long vertical lesions in the sapwood
      phloem interface at each injection point.

PMID- 16573329
TI  - Management of cottonwood leaf beetle (Coleoptera: Chrysomelidae) with a novel
      transplant soak and biorational insecticides to conserve coccinellid beetles.
AB  - Biorational foliar sprays and a novel application method of soaking transplants
      in imidacloprid were evaluated for control of adult and larval cottonwood leaf
      beetle, Chrysomela scripta F., on hybrid poplar, with emphasis on conservation of
      coccinellid predators. Foliar sprays of four biorational insecticides killed
      adult and larval C. scripta: Bacillus thuringiensis (B.t.) variety tenebrionis
      (Novodor), B.t. variety kurstaki (Raven), spinosad (Conserve SC), and
      azadirachtin (Azatin XL) (larvae only) but did not kill two species of
      coccinellids, Hippodamia convergens Guerin-Meneville and Harmonia axyridis
      (Pallas). Only imidacloprid (Admire 2) and carbaryl (Sevin XLR Plus) killed two
      species of coccinellids and adult and larval C. scripta. We evaluated a novel
      stick soak method for systemically applying imidacloprid by soaking poplar sticks
      in Admire 2 solutions of 3 and 6 ml/liter for 48 h before planting. The
      imidacloprid in the sticks was translocated to the leaves and reduced
      survivorship of adult and larval C. scripta for 10 mo without any symptoms of
      phytotoxicity. The novel stick soak method did not kill two species of
      coccinellids when foraging on leaves.

PMID- 16573330
TI  - Reduced oviposition by Diaprepes abbreviatus (Coleoptera: Curculionidae) and
      growth enhancement of citrus by Surround particle film.
AB  - Regularly applied sprays of a particle film, Surround WP, greatly enhanced the
      growth of citrus trees on a poorly drained Winder soil at Fort Pierce, FL. After
      3 yr of applications every 3 or 4 wk, Surround-treated trees had at least 5 times
      the mass, 6 times the canopy volume, and approximately 4 times the cross
      sectional area of the tree stems at the graft union compared with untreated
      trees. The larger Surround-treated trees attracted a higher number of adult
      weevil Diaprepes abbreviatus (L.) and to a lesser extent citrus root weevil,
      Pachnaeus litus (Germar), per tree, but there was an equivalent number of egg
      masses per tree compared with the control trees. The number of egg masses per
      female weevil oviposited on Surround-treated trees was significantly less than
      either the control trees or trees treated biannually with an entomopathogenic
      nematode, BioVector. The number of larvae per tree recovered from the roots of
      excavated trees was greater from trees treated with Surround once every 3 wk
      compared with control trees. The data suggest that Surround particle film greatly
      enhanced the growth of citrus trees grown in a poorly drained soil. The reduction
      in oviposition by D. abbreviatus was insufficient to significantly reduce the
      number of root weevil larvae per tree feeding on the roots. However, the more
      vigorous trees resulting from Surround applications may be more resistant or
      tolerant to root weevil feeding.

PMID- 16573331
TI  - Evaluation of insecticides and application methods against Contarinia nasturtii
      (Diptera: Cecidomyiidae), a new invasive insect pest in the United States.
AB  - The midge Contarinia nasturtii (Keiffer), a serious gall-forming insect pest of
      cruciferous plants in Europe and southwestern Asia, was first reported in the
      United States in summer 2004. It had not been recorded in North America until its
      discovery in Ontario, Canada, in 2000. Efficacy of 20 insecticides belonging to
      12 different classes was evaluated by using a foliar spray, soil drench, or seed
      treatment method. The broccoli cultivar 'Packman' was used in all tests at the
      suitable stage of four to five true leaves. Results indicated that foliar sprays
      of lambda-cyhalothrin, acephate, acetamiprid, chlorpyrifos, and methomyl reduced
      C. nasturtii larval populations by 96.7-100%. Except for acetamiprid, the other
      four insecticides also were effective against adults and provided 100% mortality
      after 24 h. When applied by drench, acetamiprid, imidacloprid, and thiamethoxam
      provided 100% control of C. nasturtii larvae, and the duration of efficacy lasted
      at least 7 wk. When applied as seed treatment, clothianidin and thiamethoxam
      provided 100% control of larvae and did not significantly affect seed
      germination. Imidacloprid also provided 100% control but the percentage of
      germination after treatment was only 62% (96.9% in check). These results indicate
      that several insecticides may significantly reduce midge populations. The
      nicotinoid class of insecticides, which has strong systemic activity, is likely
      to be the first choice. It is necessary to explore and develop other control
      methods such as cultural control and host resistance to develop an effective
      integrated pest management system.

PMID- 16573332
TI  - Identification of two subterranean termite species (Isoptera: Rhinotermitidae)
      using cellulase genes.
AB  - To identify subterranean termite species, we designed a pair of common primers
      that amplified 381-bp fragments from cDNAs encoding the endo-beta-1,4-glucanases
      (EGases) of Coptotermes formosanus Shiraki and Reticulitermes speratus (Kolbe).
      cDNAs from C. formosanus and R. speratus, and genomic DNA from R. speratus, were
      amplified by polymerase chain reaction (PCR) by using this primer pair and then
      cloned and sequenced. Sequences amplified from C.formosanus cDNA displayed 97-99%
      identity to cDNA encoding the EGase of C. formosanus (CfEG), and 92-94% identity
      to cDNA encoding the EGase of R. speratus (RsEG). By contrast, cDNA from R.
      speratus displayed 99-100% identity to RsEG cDNA and 93-94% identity to CfEG
      cDNA. CfEG and RsEG cDNAs can therefore be used as markers for the identification
      of these termite species. This is the first report of the successful
      identification of termite species by using cDNA and genomic DNA sequences of
      termite origin.

PMID- 16573333
TI  - Effects of colony composition and food type on nutrient distribution in colonies
      of Monomorium orientale (Hymenoptera: formicidae).
AB  - Monomorium orientale Mayr (Hymenoptera: Formicidae) is a common structure- and
      food-infesting ant in Asia. There is only limited information on the biology and
      habits of this species, especially on the preferred foods and distribution of
      nutrients in colonies. We conducted a laboratory study on the distribution of
      carbohydrates, proteins, and lipids, which were represented by respective food
      sources, in M. orientale colonies. Three colony conditions were applied: normal,
      with a balanced ratio of castes, queenless (only workers and brood), and
      broodless (only queens and workers). Food sources were stained to track the flow
      of the respective food in the colonies. Results revealed that carbohydrates had
      rapid distribution, with > 60% of the colony indicated in 24 h, in all colony
      conditions. Queens in all colonies did not feed on protein. Protein showed a more
      delayed distribution in the brood in all colony conditions; < 10% of the colony
      fed on protein by 24 h. Only queens in broodless colonies showed signs of feeding
      on lipid, with < 10% indicated in 24 h. Workers in all colonies fed on lipid as
      soon as it was delivered, whereas the brood only began to reveal feeding response
      after 24 h.

PMID- 16573334
TI  - Temperature effect on kinetics of uptake, transfer, and clearance of
      [14C]noviflumuron in eastern subterranean termites (Isoptera: Rhinotermitidae).
AB  - [14C]Noviflumuron uptake, clearance, rate of excretion, and transfer from treated
      to untreated termite workers were evaluated at 15,19, 23, and 27 degrees C.
      Feeding units were constructed from plastic containers provisioned with washed
      sand, distilled water, [14C]noviflumuron-treated feeding discs (0.05 or 0.5%
      [AI]), and Reticulitermes flavipes (Kollar) workers. Feeding units were held in
      environmental growth chambers preset at 15, 19, 23, and 27 degrees C. The amount
      of [14C]noviflumuron present within R. flavipes was measured by scintillation
      counting and subsequently quantified. Uptake of noviflumuron by R. flavipes
      workers at 15 degrees C was approximately 2.8 times less than at 19 or 23 degrees
      C and approximately 4.4 times less than at 27 degrees ighest uptake of
      [14C]noviflumuron occurred at 27 degrees C and 144 h. Most transfer of
      [14C]noviflumuron from treated to untreated termite workers occurred between 19
      and 27 degrees C. [14C]Noviflumuron had a half-life in R. flavipes workers of
      approximately 31-45 d, dependent on temperature. A higher amount of
      [14C]noviflumuron was lost through excretion at > or = 19 degrees C
      (approximately 15-22%) compared with 15 degrees C (0.27%). Results indicated that
      increased uptake, transfer, and clearance of noviflumuron by R. flavipes occurred
      at warmer temperatures (19-27 degrees C), and all of these processes were
      significantly lower at 15 degrees C.

PMID- 16573335
TI  - Establishment of baseline susceptibility data to various insecticides for
      Homalodisca coagulata (Homoptera: Cicadellidae) by comparative bioassay
      techniques.
AB  - Homalodisca coagulata Say, adults from three locations in California were
      subjected to insecticide bioassays to establish baseline toxicity. Initially, two
      bioassay techniques, petri dish and leaf dip, were compared to determine the most
      useful method to establish baseline susceptibility data under laboratory and
      greenhouse conditions. Comparative dose-response data were determined by both
      techniques to endosulfan, dimethoate, cyfluthrin, and acetamiprid. Toxic values
      were similar to some insecticides with both techniques but not for all
      insecticides, revealing susceptibility differences among the three populations of
      H. coagulata. In subsequent tests, the petri dish technique was selected to
      establish baseline susceptibility data to various contact insecticides. A
      systemic uptake bioassay was adapted to estimate dose-mortality responses to a
      systemic insecticide, imidacloprid. A 2-yr comparison of toxicological responses
      showed all three populations of H. coagulata to be highly susceptible to 10
      insecticides, including chlorpyrifos, dimethoate, endosulfan, bifenthrin,
      cyfluthrin, esfenvalerate, fenpropathrin, acetamiprid, imidacloprid, and
      thiamethoxam. In general, two pyrethroids, bifenthrin and esfenvalerate, were the
      most toxic compounds, followed by two neonicotinoids, acetamiprid and
      imidacloprid. The LC50 values for all insecticides tested were lower than
      concentrations used as recommended field rates. Baseline data varied for the
      three geographically distinct H. coagulata populations with the petri dish
      technique. Adult H. coagulata collected from San Bernardino County were
      significantly more susceptible to select pyrethroids compared with adults from
      Riverside or Kern counties. Adults from San Bernardino County also were more
      sensitive to two neonicotinoids, acetamiprid and imidacloprid. The highest LC50
      values were to endosulfan, which nonetheless proved highly toxic to H. coagulata
      from all three regions. In the majority of the tests, mortality increased over
      time resulting in increased susceptibility at 48 h compared with 24 h. These
      results indicate a wide selection of highly effective insecticides that could aid
      in managing H. coagulata populations in California.

PMID- 16573336
TI  - Population dynamics and gene flow of Helicoverpa armigera (Lepidoptera:
      Noctuidae) on cotton and grain crops in the Murrumbidgee Valley, Australia.
AB  - The population dynamics of Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae)
      in the Murrumbidgee Valley, Australia, has been characterized using five highly
      variable microsatellite loci. In the 2001-2002 growing season, there were very
      high levels of migration into the Murrumbidgee Valley with no detectable genetic
      structuring, consistent with previous analyses on a national scale. By contrast,
      there was significant genetic structuring over the 2002-2003 growing season, with
      three distinct genetic types detected. The first type corresponded to the first
      two generations and was derived from local individuals emerging from diapause and
      their progeny. The second genetic type corresponded to generation 3 and resulted
      from substantial immigration into the region. There was another genetic shift in
      generation 4, which accounts for the third genetic type of the season. This
      genetic shift occurred despite low levels of immigration. During the third
      generation of the 2002-2003 growing season, different population dynamics was
      characterized for H. armigera on maize, Zea mays L., and cotton Gossipium
      hirsutum L. Populations on cotton tended to cycle independently with very little
      immigration from outside the region or from maize within the region. Maize acted
      as a major sink for immigrants from cotton and from outside the region. If
      resistance were to develop on cotton under these circumstances, susceptible
      individuals from maize or from other regions would not dilute this resistance. In
      addition, resistance is likely to be transferred to maize and be perpetuated
      until diapause, from where it may reemerge next season. If low levels of
      immigration were to occur on transgenic cotton, this may undermine the
      effectiveness of refugia, especially noncotton refugia.

PMID- 16573337
TI  - Susceptibilities of Helicoverpa zea and Heliothis virescens (Lepidoptera:
      Noctuidae) populations to Cry1Ac insecticidal protein.
AB  - Susceptibilities of bollworm, Helicoverpa zea (Boddie) and tobacco budworm,
      Heliothis virescens (F.) to Cry1Ac were measured via a diet-incorporated assay
      with MPV II at the University of Arkansas during 2002-2004. Lethal concentration
      mortality (LC50) estimates of five laboratory, seven laboratory-cross, and 10
      field populations of H. virescens varied 12-fold. Pooled susceptibilities of H.
      virescens across all laboratory and field populations varied five-fold. The LC50
      estimates for H. virescens were higher than those reported by previous research
      before the introduction of transgenic crops. However, the ratio of susceptibility
      of laboratory and field populations was similar, suggesting no change in overall
      species susceptibility. Individual LC50 estimates of five laboratory, nine
      laboratory-cross, and 57 field populations of H. zea varied over 130-fold. Pooled
      susceptibilities across laboratory and field populations varied widely. Among the
      field populations, colonies from non-Bacillus thuringiensis (Bt) crops were
      generally more susceptible than those from Bt crops. Across the Bt crops
      expressing Cry protein, colonies from Bollgard (Monsanto Company) cotton had
      lower susceptibility to CrylAc than those from Bt corn and those from non-Bt
      crops.

PMID- 16573338
TI  - Monitoring of diamondback moth (Lepidoptera: Plutellidae) resistance to spinosad,
      indoxacarb, and emamectin benzoate.
AB  - Six to nine populations of the diamondback moth, Plutella xylostella (L.), were
      collected annually from fields of crucifer vegetables in the United States and
      Mexico from 2001 to 2004 for baseline susceptibility tests and resistance
      monitoring to spinosad, indoxacarb, and emamectin benzoate. A discriminating
      concentration for resistance monitoring to indoxacarb and emamectin benzoate was
      determined based on baseline data in 2001 and was used in the diagnostic assay
      for each population in 2002-2004 together with a discriminating concentration for
      spinosad determined previously. Most populations were susceptible to all three
      insecticides, but a population from Hawaii in 2003 showed high levels of
      resistance to indoxacarb. Instances of resistance to spinosad occurred in Hawaii
      (2000), Georgia (2001), and California (2002) as a consequence of a few years of
      extensive applications in each region. The collaborative monitoring program
      between university and industry scientists we discuss in this article has
      provided useful information to both parties as well as growers who use the
      products. These studies provide a baseline for developing a more effective
      resistance management program for diamondback moth.

PMID- 16573339
TI  - Prevention of mosquitoes (Diptera: Culicidae) and house flies (Diptera: Muscidae)
      from entering simulated aircraft with commercial air curtain units.
AB  - Commercially available air curtain units were used to create air barriers to
      prevent mosquitoes and house flies from entering a simulated aircraft doorway
      together with passengers. Two assemblies of simulated passenger bridge and
      aircraft were constructed, and airflow measurements were recorded to confirm
      airflow characteristics for several combinations of commercial units. Three
      mosquito species were selected for different host-seeking characteristics, and
      house flies were selected to represent a large, strong-flying insect. Batches of
      20 or 200 insects of four species were released into the passenger bridge just
      before 25 persons passed through the assembly, then insects that entered the
      aircraft cabin were recovered. Results showed that horizontal plus vertical or
      vertical-mounted air curtain units with the airflow directed at a 45 degrees
      angle into the passenger bridge excluded 95-99% of the mosquitoes and 95-100% of
      the house flies, respectively. Airflows were measured and estimated to be
      effective if the mean was > 4 m/s in the critical area in the center of the
      converging airflows. The study validates the concept that air barriers can
      effectively prevent the passage of flying insects into an aircraft.

PMID- 16573340
TI  - Comparative susceptibility of European corn borer, southwestern corn borer, and
      sugarcane borer (Lepidoptera: Crambidae) to Cry1Ab protein in a commercial
      Bacillus thuringiensis corn hybrid.
AB  - One field strain each of the European corn borer, Ostrinia nubilalis (Hubner);
      southwestern corn borer, Diatraea grandiosella Dyar; and sugarcane borer,
      Diatraea saccharalis (F.); were collected from cornfields in northeastern
      Louisiana. Susceptibilities of the field strain and a corresponding laboratory
      strain of the three borer species to Cry1Ab protein in DK69-70 Bacillus
      thuringiensis (Bt) corn hybrid were determined by exposing neonates to intact
      leaf tissues from whorl stage plants or by feeding neonates or third instars on a
      meridic diet treated with different concentrations of Cry1lAb protein extracted
      from Bt corn leaves. Mortality and growth of larvae were evaluated after 2 and 4
      d posttreatment in the bioassays by using intact leaf tissues or after 7 d in the
      bioassays by using diet incorporating Cry1Ab protein. D. saccharalis was the
      least susceptible species to Cry1Ab protein among the three species, followed by
      D. grandiosella, whereas O. nubilalis was most susceptible. The 2-d mortality of
      D. saccharalis neonates on intact Bt leaf tissues was lower than that of O.
      nubilalis and D. grandiosella. All neonates of O. nubilalis were killed on the
      diet treated with Cry1Ab protein at 0.5 and 1 mg/kg. The mortality of D.
      grandiosella was > 75% at 1 mg/kg, but it was < 6% for D. saccharalis at 1 mg/kg.
      The LC50 values of D. saccharalis were 3- and 11-fold higher than those of D.
      grandiosella and O. nubilalis, respectively. The LC90 values of D. saccharalis
      were 8- and 32-fold higher than those of D. grandiosella and O. nubilalis,
      respectively. Larval growth of the three species on Cry1Ab-treated diet was
      inhibited, but the inhibition was greater for O. nubilalis and D. grandiosella
      than for D. saccharalis. The lower susceptibility of D. saccharalis to Cry1Ab
      protein suggests that it is necessary to verify if a high-dose Bt corn for O.
      nubilalis and D. grandiosella is also a high dose for D. saccharalis.

PMID- 16573341
TI  - Evaluation of cool- and warm-season grasses for resistance to multiple chinch bug
      (Hemiptera: Blissidae) species.
AB  - Chinch bugs are common pests of many agronomic and horticulturally important
      crops and turfgrasses. The extensive overlap of plant hosts and geographic
      distribution of Blissus leucopterus leucopterus (Say), Blissus leucopterus hirtus
      Montandon, Blissus insularis Barber, and Blissus occiduus Barber underscores the
      importance of identifying resistant germplasm. Cool- and warm-season turfgrasses
      and sorghum, Sorghum bicolor (L.) Moench, were evaluated for resistance to chinch
      bugs in the Blissus complex, and the presence of multiple resistance was
      documented. Greenhouse studies established that B. occiduus-resistant
      ('Prestige', formerly NE91-118) and -susceptible ('378') buffalograsses,, Buchloe
      dactyloides (Nuttall) Engelmann, were susceptible to all other chinch bug
      species. KS94 sorghum exhibited resistance to both B. occiduus and B. l.
      leucopterus, whereas B. insularis-resistant St. Augustinegrass, Stenotaphrum
      secundatum (Walter) Kuntze ('Floratam'), was also resistant to B. occiduus. B. l.
      leucopterus-susceptible sorghum ('Wheatland') and B. insularis-susceptible St.
      Augustinegrasses ('Raleigh' and 'Amerishade') were highly resistant to B.
      occiduus. Endophyte-free and -enhanced fine fescues (Festuca spp.) were
      moderately to highly susceptible to B. l. hirtus but moderately to highly
      resistant to B. occiduus. The results of this research showed the buffalograsses
      evaluated, including B. occiduus-resistant Prestige, are moderately to highly
      susceptible to the three other chinch bug species. In contrast, B. occiduus did
      not cause considerable damage to any of the turfgrasses or sorghum cultivars
      evaluated, other than buffalograss, irrespective of whether or not they are
      resistant to another chinch bug species. This information is increasingly
      important as various grasses become adapted to regions that may possess chinch
      bug species other than those with which they are typically associated. These
      levels of Blissus resistance should be included when selecting resistant
      germplasm for managing Blissus species pests.

PMID- 16573342
TI  - Chinch bug (Hemiptera: Blissidae) mouthpart morphology, probing frequencies, and
      locations on resistant and susceptible germplasm.
AB  - Chinch bugs are common pests of many agronomic and horticulturally important
      crops and turfgrasses. Previous research has indicated that some grasses exhibit
      resistance to multiple chinch bug species, whereas others are resistant to only
      one species. The objectives of this research were to document differences in the
      probing frequencies and locations among Blissus species as well as differences in
      mouthpart morphology as a first step in understanding the differential responses
      of grasses to chinch bug feeding. Scanning electron microscopy detected
      differences in the total lengths of proboscises as well as individual mouthpart
      segments among the four species studied. Blissus occiduus Barber probed
      significantly more often on buffalograss, Buchloe dactyloides (Nuttall)
      Engelmann, than any other plant material. Probing locations of B. occiduus and
      Blissus leucopterus leucopterus (Say) were similar on both B. occiduus-resistant
      and susceptible buffalograsses and KS94 sorghum, Sorghum bicolor (L.) Moench (B.
      occiduus-resistant, B. l. leucopterus-resistant). However, on 'Wheatland' sorghum
      (B. occiduus-resistant, B. l. leucopterus-susceptible), stylet tracts of B. l.
      leucopterus most often terminated in the bundle sheath cells, whereas those of B.
      occiduus generally terminated in the vascular tissues.

PMID- 16573343
TI  - Physiological responses of resistant and susceptible buffalograsses to Blissus
      occiduus (Hemiptera: Blissidae) feeding.
AB  - The impact of Blissus occiduus Barber feeding on resistant ('Prestige') and
      susceptible ('378') buffalograsses, Buchloe dactyloides (Nuttall) Engelmann, was
      evaluated through measurement of carbon exchange rate, light and carbon
      assimilation (A-C(i)) curves, chlorophyll a fluorescence, and nonstructural
      carbohydrates. No significant differences in carbon exchange rates were observed
      between infested and control plants for 378 at 5 and 10 d after infestation;
      however, at 20 d after chinch bug introduction, significant differences in carbon
      exchange rates between infested and control 378 plants were detected. Carbon
      exchange rates were similar between infested and control Prestige plants at 5,10,
      and 20 d after infestation, suggesting that resistant plants can allocate energy
      for recovery from chinch bug injury. Significant differences in the photochemical
      efficiency of photosystem II (PSII) and the apparent photosynthetic electron
      transport ratio were observed between infested and control 378 plants, whereas,
      no significant differences in the photochemical efficiency of PSII and the
      electron transport ratio were detected between control and infested Prestige
      plants. Blissus occiduus-infested 378 and Prestige plants consistently had
      similar or higher levels of nonstructural carbohydrates compared with their
      respective control plants. These data suggest that both resistant and susceptible
      buffalograsses increase levels of nonstructural carbohydrates in response to B.
      occiduus feeding. This research also suggests compensatory photosynthesis takes
      place in Prestige but not in 378.

PMID- 16573344
TI  - Acaricidal effect of a diatomaceous earth formulation against Tyrophagus
      putrescentiae (Astigmata: Acaridae) and its predator Cheyletus malaccensis
      (Prostigmata: Cheyletidae) in four grain commodities.
AB  - Laboratory bioassays were conducted to evaluate the effect of the diatomaceous
      earth (DE) formulation SilicoSec (Biofa GmbH, Munsingen, Germany), against two
      stored-product mite species, Tyrophagus putrescentiae (Shrank) and the predator
      Cheyletus malaccensis Oudemans. For this purpose, DE was applied in wheat, oat,
      rye, and maize, at the dose rates 0, 0.5, 1, and 2 g/kg grain. The mortality of
      the exposed mites was assessed after 24 h, 48 h, 7 d, and 14 d of exposure in the
      treated substrate. After this interval, the treated grains were checked for
      oviposition or progeny. The tests were conducted at 80% RH and at two
      temperatures, 20 and 25 degrees C. Generally, for both species, mortality was
      higher at 25 degrees C than at 20 degrees C. For T. putrescentiae, at both
      temperatures, the mortality in grains treated with the highest DE rate was 100%
      after only 24 h of exposure, with the exception of maize at 20 degrees C, where
      mortality was 91.7%. The mortality of C. malaccensis after 24 h of exposure to
      the treated grains, in the absence of prey, did not exceed 29% at any of the
      temperature- grain-dose combinations, whereas no mites were dead in rye and maize
      treated with 0.5 and 1 g of DE. Even after 14 d of exposure at the highest DE
      rate, mite mortality did not reach 100%. The presence of T. putrescentiae
      individuals as prey in the treated substrate enhanced C. malaccensis survival.
      Hence, after 14 d of exposure, the mortality of C. malaccensis, in wheat, oat,
      rye, and maize treated with the highest DE rate was 51.7, 59.7, 70, and 36.9,
      respectively. No progeny production was recorded in the treated substrate for T.
      putrescentiae; in contrast, oviposition and F1 progeny were recorded for C.
      malaccensis. Our results suggest that the use of C. malaccensis with low doses of
      DE may be an appealing integrated pest management (IPM) approach against T.
      putrescentiae, and probably against other stored-grain mite species.

PMID- 16573345
TI  - Life tables of Venturia canescens (Hymenoptera: Ichneumonidae) parasitizing the
      Mediterranean flour moth (Lepidoptera: Pyralidae).
AB  - Effects of temperature, adult feeding, and host instar on life table parameters
      of Venturia canescens Gravenhorst (Hymenoptera: Ichneumonidae) parasitizing
      larvae of Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) were studied in the
      laboratory. Experimental adults lived under various regimes of temperature (15,
      20, 25, and 30 degrees C), food supply (with or without access to honey), and
      host instar (second, third, fourth, and fifth). Temperature increase resulted in
      higher values of the intrinsic rate of natural increase (r(m)), the net
      reproductive rate (R(o)), the finite capacity of increase (lambda), and the gross
      reproductive rate (GRR), whereas it was followed by decrease of the mean
      generation time (G) and the doubling time (DT) values. Feeding on honey caused
      remarkable increase of r(m), R(o), and GRR, whereas r(m) and lambda reached their
      maximum when full-grown hosts (fifth instar) were parasitized. This is the first
      time life table parameters of V. canescens have been studied. The findings of the
      current study are discussed on the basis of improving V. canescens performance as
      a biological agent against moth pests of stored products.

PMID- 16573346
TI  - Geophone detection of subterranean termite and ant activity.
AB  - A geophone system was used to monitor activity of subterranean termites and ants
      in a desert environment with low vibration noise. Examples of geophone signals
      were recorded from a colony of Rhytidoponera taurus (Forel), a colony of
      Camponotus denticulatus Kirby, and a termite colony (undetermined Drepanotermes
      sp.) under attack by ants from a nearby C. denticulatus colony. The geophone
      recordings were compared with signals recorded from accelerometers in a citrus
      grove containing Solenopsis invicta Buren workers. Because of their small size,
      all of these insects produce relatively weak sounds. Several different types of
      insect-generated sounds were identified in the geophone recordings, including
      high-frequency ticks produced by R. taurus and C. denticulatus, and patterned
      bursts of head bangs produced by Drepanotermes. The S. invicta produced bursts of
      ticks with three different stridulation frequencies, possibly produced by three
      different-sized workers. Overall, both systems performed well in enabling
      identification of high-frequency or patterned pulses. The geophone was more
      sensitive than the accelerometer to low-frequency signals, but low-frequency
      insect sound pulses are more difficult to distinguish from background noises than
      high-frequency pulses. The low cost of multiple-geophone systems may facilitate
      development of future applications for wide-area subterranean insect monitoring
      in quiet environments.

PMID- 16573347
TI  - The future of antisense oligonucleotides in the treatment of respiratory
      diseases.
AB  - Antisense oligonucleotides (ASO) are short synthetic DNA molecules designed to
      inhibit translation of a targeted gene to protein via interaction with messenger
      RNA. More recently, small interfering (si)RNA have been developed as potent tools
      to specifically inhibit gene expression. ASO directed against signaling
      molecules, cytokine receptors, and transcription factors involved in allergic
      immune and inflammatory responses, have been applied in experimental models of
      asthma and demonstrate potential as therapeutics. Several ASO-based drugs
      directed against oncogenes have been developed for therapy of lung cancer, and
      some have recently reached clinical trials. ASO and siRNA to respiratory
      syncytial virus infection have demonstrated good potential to treat this
      condition, particularly in combination with an antiviral drug. Although ASO-based
      therapeutics are promising for lung diseases, issues of specificity,
      identification of correct molecular targets, delivery and carrier systems, as
      well as potential adverse effects must be carefully evaluated before clinical
      application.

PMID- 16573348
TI  - Mechanistic rationale and clinical evidence for the efficacy of proteasome
      inhibitors against indolent and mantle cell lymphomas.
AB  - Recent advances in understanding the complex biology of the ubiquitin-proteasome
      pathway have led to the identification of many potentially 'drugable' targets
      within this pathway. One such inhibitor, bortezomib (formerly known as PS341),
      has proven to be an effective reversible inhibitor of the chymotryptic protease
      in the 26S proteasome. Proteasome inhibitors represent a new approach for the
      treatment of many forms of cancer, especially select hematological malignancies.
      The proteasome plays an important role in regulating the availability of
      different intracellular proteins. While only some of the consequences of
      inhibiting this activity are understood, a growing amount of data suggests that
      inhibition of the proteasome is associated with a remarkable panoply of different
      biological effects that include cell cycle arrest, apoptosis, changes in cell
      surface adhesion markers, and an increased sensitivity to standard chemotherapy
      and radiation therapy. Bortezomib was recently approved by the US FDA for the
      treatment of relapsed or refractory multiple myeloma. In addition, bortezomib has
      also shown encouraging results in the treatment of select types of non-Hodgkin
      lymphomas (NHLs). Ongoing phase II clinical trials in pretreated patients are
      exploring bortezomib in different histologies of NHLs and in combination with
      conventional chemotherapy. Preliminary data have shown interesting activity,
      especially in patients with follicular, marginal zone, and mantle cell lymphoma;
      in these populations, durable complete and partial remissions have been reported.
      The toxicity profile of this drug, coupled with its unusual mechanism of action,
      make it a potentially important agent warranting further preclinical and clinical
      attention. However, many unanswered questions remain regarding how best to employ
      bortezomib in the conventional treatment of lymphoma. The apparent lack of
      activity in different subtypes of lymphoma, such as small lymphocytic
      lymphoma/chronic lymphocytic leukemia and diffuse large B-cell lymphoma, as well
      as a lack of understanding about the best way to combine bortezomib with standard
      therapies for indolent NHLs, raises important questions regarding the mechanistic
      basis for its effects. We will undoubtedly need to understand these effects
      better in order to fully exploit the potential of this new class of drugs.

PMID- 16573349
TI  - Understanding and applying regulatory guidance on the nonclinical development of
      biotechnology-derived pharmaceuticals.
AB  - Biotechnology-derived pharmaceuticals are a well established and growing part of
      the therapeutic armamentarium. Beginning with recombinant versions of products
      such as insulin that were previously manufactured by extraction from animal and
      human sources, licensed biotechnology drugs and those in development now span an
      ever-increasing range of product types and therapeutic categories. As a
      consequence of this diversity, both general and product class-specific scientific
      guidelines have been developed on a regional (e.g. EU/US) or international (e.g.
      ICH - International Conference on Harmonization) basis. The current portfolio of
      nonclinical guidelines, particularly ICH S6, emphasizes flexibility and
      adaptability to the specific circumstances of the individual biotechnology
      product and its intended indication, taking into account factors not generally
      applicable to small-molecule drugs, such as pharmacodynamic responsiveness of
      safety and efficacy models, species specificity, and antibody formation.
      Guidelines developed principally with small-molecule drugs in mind may,
      nevertheless, have some applicability to biotechnology drugs on issues such as
      safety pharmacology, as well as on regulatory, procedural and dossier submission
      requirements. Scientific guidelines, such as those providing nonclinical
      guidance, are just one, albeit important, component of an increasingly complex
      legal/scientific environment in drug development.

PMID- 16573350
TI  - Abatacept.
AB  - Abatacept (Orencia) is the first in a new class of biologics known as selective
      costimulation modulators. It inhibits full activation of T cells and interacts
      with other cell types to affect additional mediators of the inflammatory cascade.
      The clinical efficacy of abatacept in patients with active rheumatoid arthritis,
      despite prior treatment with methotrexate or anti-tumor necrosis factor-alpha
      (anti-TNFalpha) therapies, has been investigated in two randomized, double-blind,
      placebo-controlled, multicenter, phase III trials of 6 or 12 months' duration. In
      these trials, patients received intravenous abatacept (fixed-dose regimen based
      on bodyweight) or placebo in addition to background disease-modifying anti
      rheumatic drugs (DMARDs) other than anti-TNFalpha therapies. Relative to placebo,
      abatacept significantly improved signs and symptoms of disease assessed using
      American College of Rheumatology (ACR) 20, 50, and 70 criteria and specific
      improvement in physical function as measured by the Health Assessment
      Questionnaire Disability Index at 6 months and significantly slowed structural
      damage progression in joints at 12 months. Improvements in ACR 20, 50, and 70
      response rates were maintained at the final assessment in the 12-month trial.
      Abatacept infusions were generally well tolerated. Acute infusion-related
      reactions occurred in 9% of abatacept and 6% of placebo recipients in phase III
      trials. Integrated safety data from five clinical trials showed that serious
      adverse events were reported in 13.6% of abatacept and 12.3% of placebo
      recipients and the incidence of serious infections was 3.0% and 1.9%. Abatacept
      administered with background biologic DMARDs appears to be less well tolerated
      than abatacept plus background nonbiologic DMARDs.

PMID- 16573353
TI  - Spotlight on eptifibatide in patients with acute coronary syndromes and/or
      undergoing percutaneous coronary intervention.
AB  - Eptifibatide (Integrilin) is a highly specific, reversible, intravenously
      administered glycoprotein IIb/IIIa receptor antagonist that acts at the final
      common step of the platelet aggregation pathway. Data from large clinical trials
      indicate that intravenous eptifibatide as adjunctive therapy to standard care is
      effective in patients with non-ST-segment elevation (NSTE) acute coronary
      syndromes (ACS) and/or undergoing percutaneous coronary intervention (PCI). In
      the ESPRIT (Enhanced Suppression of the Platelet glycoprotein IIb/IIIa Receptor
      with Integrilin Therapy) trial in patients undergoing PCI with stenting,
      eptifibatide, compared with placebo, achieved significant reductions in death and
      ischemic complications and was better than a strategy of reserving treatment for
      the bailout situation. In the large PURSUIT (Platelet IIb/IIIa in Unstable
      angina: Receptor Suppression Using Integrilin Therapy) trial in patients with
      NSTE ACS, eptifibatide was associated with a significant reduction in the
      incidence of death or myocardial infarction (MI) compared with placebo.
      Eptifibatide is well tolerated in these trials. Ongoing trials are currently
      investigating the efficacy and tolerability of regimens that include this agent
      in other indications, including ST-segment elevation MI.

PMID- 16573354
TI  - Spotlight on infliximab in Crohn disease and rheumatoid arthritis.
AB  - Infliximab (Remicade) is a chimeric monoclonal antibody against tumor necrosis
      factor (TNF)-alpha that has shown efficacy in Crohn disease and rheumatoid
      arthritis with a disease-modifying activity and rapid onset of action. It is
      administered intravenously, generally in a schedule with initial infusions at 0,
      2, and 6 weeks, followed by administration once every 8 weeks. Infliximab is
      effective in the treatment of patients with moderately to severely active Crohn
      disease with an inadequate response to other treatment options or those with
      fistulizing disease. In combination with methotrexate, infliximab reduced signs
      and symptoms and delayed disease progression in patients with active,
      methotrexate-refractory rheumatoid arthritis and in those with early disease. The
      drug was generally well tolerated. Recrudescence of tuberculosis infection and
      worsening of heart failure and demyelinating disease are among some of the
      concerns with anti-TNFalpha therapy, requiring cautious use of these agents in
      high-risk patients. Current data suggest that infliximab may be cost effective,
      especially when long-term clinical outcomes and burden of the diseases are taken
      into account. More robust, prospective pharmacoeconomic studies are required to
      better ascertain the cost effectiveness of infliximab. Direct head-to-head
      comparative trials of infliximab with other biological agents are not yet
      available and would be helpful in determining with greater certainty the place of
      infliximab in the management of these diseases. Nonetheless, infliximab, like
      other biological agents, is a valuable treatment option in patients with
      moderately to severely active Crohn disease (including fistulizing disease) or
      rheumatoid arthritis (including early disease).

PMID- 16573355
TI  - Lactic acid and exercise performance : culprit or friend?
AB  - This article critically discusses whether accumulation of lactic acid, or in
      reality lactate and/or hydrogen (H+) ions, is a major cause of skeletal muscle
      fatigue, i.e. decline of muscle force or power output leading to impaired
      exercise performance. There exists a long history of studies on the effects of
      increased lactate/H+ concentrations in muscle or plasma on contractile
      performance of skeletal muscle. Evidence suggesting that lactate/H+ is a culprit
      has been based on correlation-type studies, which reveal close temporal
      relationships between intramuscular lactate or H+ accumulation and the decline of
      force during fatiguing stimulation in frog, rodent or human muscle. In addition,
      an induced acidosis can impair muscle contractility in non-fatigued humans or in
      isolated muscle preparations, and several mechanisms to explain such effects have
      been provided. However, a number of recent high-profile papers have seriously
      challenged the 'lactic acid hypothesis'. In the 1990s, these findings mainly
      involved diminished negative effects of an induced acidosis in skinned or intact
      muscle fibres, at higher more physiological experimental temperatures. In the
      early 2000s, it was conclusively shown that lactate has little detrimental effect
      on mechanically skinned fibres activated by artificial stimulation. Perhaps more
      remarkably, there are now several reports of protective effects of lactate
      exposure or induced acidosis on potassium-depressed muscle contractions in
      isolated rodent muscles. In addition, sodium-lactate exposure can attenuate
      severe fatigue in rat muscle stimulated in situ, and sodium lactate ingestion can
      increase time to exhaustion during sprinting in humans. Taken together, these
      latest findings have led to the idea that lactate/H+ is ergogenic during
      exercise. It should not be taken as fact that lactic acid is the deviant that
      impairs exercise performance. Experiments on isolated muscle suggest that
      acidosis has little detrimental effect or may even improve muscle performance
      during high-intensity exercise. In contrast, induced acidosis can exacerbate
      fatigue during whole-body dynamic exercise and alkalosis can improve exercise
      performance in events lasting 1-10 minutes. To reconcile the findings from
      isolated muscle fibres through to whole-body exercise, it is hypothesised that a
      severe plasma acidosis in humans might impair exercise performance by causing a
      reduced CNS drive to muscle.

PMID- 16573356
TI  - Vegetarian diets : nutritional considerations for athletes.
AB  - The quality of vegetarian diets to meet nutritional needs and support peak
      performance among athletes continues to be questioned. Appropriately planned
      vegetarian diets can provide sufficient energy and an appropriate range of
      carbohydrate, fat and protein intakes to support performance and health. The
      acceptable macronutrient distribution ranges for carbohydrate, fat and protein of
      45-65%, 20-35% and 10-35%, respectively, are appropriate for vegetarian and non
      vegetarian athletes alike, especially those who perform endurance events.
      Vegetarian athletes can meet their protein needs from predominantly or
      exclusively plant-based sources when a variety of these foods are consumed daily
      and energy intake is adequate. Muscle creatine stores are lower in vegetarians
      than non-vegetarians. Creatine supplementation provides ergogenic responses in
      both vegetarian and non-vegetarian athletes, with limited data supporting greater
      ergogenic effects on lean body mass accretion and work performance for
      vegetarians. The potential adverse effect of a vegetarian diet on iron status is
      based on the bioavailability of iron from plant foods rather than the amount of
      total iron present in the diet. Vegetarian and non-vegetarian athletes alike must
      consume sufficient iron to prevent deficiency, which will adversely affect
      performance. Other nutrients of concern for vegetarian athletes include zinc,
      vitamin B12 (cyanocobalamin), vitamin D (cholecalciferol) and calcium. The main
      sources of these nutrients are animal products; however, they can be found in
      many food sources suitable for vegetarians, including fortified soy milk and
      whole grain cereals. Vegetarians have higher antioxidant status for vitamin C
      (ascorbic acid), vitamin E (tocopherol), and beta-carotene than omnivores, which
      might help reduce exercise-induced oxidative stress. Research is needed comparing
      antioxidant defences in vegetarian and non-vegetarian athletes.

PMID- 16573357
TI  - The impact of exercise training intensity on change in physiological function in
      patients with chronic obstructive pulmonary disease.
AB  - Pulmonary rehabilitation incorporating exercise training is an effective method
      of enhancing physiological function and quality of life for patients with chronic
      obstructive pulmonary disease (COPD). Despite the traditional belief that
      exercise is primarily limited by the inability to adequately increase ventilation
      to meet increased metabolic demands in these patients, significant deficiencies
      in muscle function, oxygen delivery and cardiac function are observed that
      contribute to exercise limitation. Because of this multifactorial exercise
      limitation, defining appropriate exercise training intensities is difficult. The
      lack of a pure cardiovascular limitation to exercise prohibits the use of
      training guidelines that are based on cardiovascular factors such as oxygen
      consumption or heart rate. Current recommendations for exercise training
      intensity for patients with COPD include exercising at a 'maximally tolerable
      level', at an intensity corresponding with 50% of peak oxygen consumption (V
      O2peak), or at 60-80% of peak power output obtained on a symptom-limited exercise
      tolerance test. In general, it appears that higher intensity training elicits
      greater physiological change than lower intensity training; however, there is no
      consensus as to the exercise training intensity that elicits the greatest
      physiological benefit while remaining tolerable to patients. The 'optimal'
      intensity of training likely depends upon the individual goals of each patient.
      If the goal is to increase the ability to sustain tasks that are currently able
      to be performed, lower to moderate-intensity training is likely to be sufficient.
      If the goal of training, however, is to increase the ability to perform tasks
      that are above the current level of tolerance, higher intensity training is
      likely to elicit greater performance increases. In order to perform higher
      intensity exercise, an interval training model is likely required. High-intensity
      interval training involves significant anaerobic energy utilisation and,
      therefore, may better mimic the physiological requirements of activities of daily
      living. Also, high-intensity interval training is tolerable to patients and may,
      in fact, reduce the degree of dyspnoea and dynamic hyperinflation through a
      reduced ventilatory demand. Another factor that will determine the optimal
      intensity of training is the relative contribution of ventilatory limitation to
      exercise tolerance. If peak exercise tolerance is limited by a patient's ability
      to increase ventilation, it is possible that interval training at an intensity
      higher than peak will elicit greater muscular adaptation than an intensity at or
      below peak power on an incremental exercise test. More research is required to
      determine the optimal training intensity for pulmonary rehabilitation patients.

PMID- 16573359
TI  - Physical activity levels of children during school playtime.
AB  - School represents a suitable setting for intervention programmes aiming to
      promote physical activity to benefit health. During the school day, physical
      education and school playtime offer children regular opportunities to engage in
      physical activity. However, there is growing concern that, internationally,
      curricular time allocated to physical education is not meeting statutory
      guidelines. The effectiveness of the playground environment to promote physical
      activity has been considered as a complementary setting to physical education.
      Physical activity guidelines state that children should engage in at least 1 hour
      of moderate intensity physical activity a day. Currently no empirically tested
      guidelines exist for physical activity levels during playtime. However, studies
      cited in this article indicate that playtime can contribute between 5-40% of
      recommended daily physical activity levels when no interventions have been
      utilised. The limited school-based investigations that have been reported in the
      literature suggest that boys engage in more physical activity during playtime
      than girls. Studies that have implemented intervention strategies in order to
      promote physical activity levels indicate that playtime can substantially
      contribute towards daily optimal physical activity guidelines. Energy expenditure
      and physical activity levels have increased during playtime following the
      implementation of playtime-based interventions. In order to advance knowledge of
      children's physical activity during playtime, a number of key issues for
      consideration in future research are detailed. Research on children's use of
      playtime to be physically active and the extent of the contribution of playtime
      to daily physical activity guidelines is warranted.

PMID- 16573360
TI  - Modelling malaria control.

PMID- 16573361
TI  - Lessons on ethical decision making from the bioscience industry.

PMID- 16573362
TI  - What is the bioscience industry doing to address the ethical issues it faces?

PMID- 16573358
TI  - Oxidative stress : relationship with exercise and training.
AB  - Free radicals are reactive compounds that are naturally produced in the human
      body. They can exert positive effects (e.g. on the immune system) or negative
      effects (e.g. lipids, proteins or DNA oxidation). To limit these harmful effects,
      an organism requires complex protection - the antioxidant system. This system
      consists of antioxidant enzymes (catalase, glutathione peroxidase, superoxide
      dismutase) and non-enzymatic antioxidants (e.g. vitamin E [tocopherol], vitamin A
      [retinol], vitamin C [ascorbic acid], glutathione and uric acid). An imbalance
      between free radical production and antioxidant defence leads to an oxidative
      stress state, which may be involved in aging processes and even in some pathology
      (e.g. cancer and Parkinson's disease). Physical exercise also increases oxidative
      stress and causes disruptions of the homeostasis. Training can have positive or
      negative effects on oxidative stress depending on training load, training
      specificity and the basal level of training. Moreover, oxidative stress seems to
      be involved in muscular fatigue and may lead to overtraining.

PMID- 16573363
TI  - Mathematical model of HPV provides insight into impacts of risk factors and
      vaccine.

PMID- 16573364
TI  - Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of
      vaccination: mathematical modelling analyses.
AB  - BACKGROUND: Candidate human papillomavirus (HPV) vaccines have demonstrated
      almost 90%-100% efficacy in preventing persistent, type-specific HPV infection
      over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention
      of precancerous lesions in phase III clinical trials, they will be licensed for
      public use in the near future. How these vaccines will be used in countries with
      national cervical cancer screening programmes is an important question. METHODS
      AND FINDINGS: We developed a transmission model of HPV 16 infection and
      progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence
      over time. The model was used to estimate the transmission probability of the
      virus, to look at the effect of changes in patterns of sexual behaviour and
      smoking on age-specific trends in cancer incidence, and to explore the impact of
      HPV 16 vaccination. We estimated a high per-partnership transmission probability
      of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour
      and smoking accounted, in part, for the increase seen in cervical cancer
      incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in
      opportunistic immunisation) and high (90% in a national immunisation programme)
      coverage of the adolescent population, vaccinating women and men had little
      benefit over vaccinating women alone. We estimate that vaccinating 90% of young
      women before sexual debut has the potential to decrease HPV type-specific (e.g.,
      type 16) cervical cancer incidence by 91%. If older women are more likely to have
      persistent infections and progress to cancer, then vaccination with a duration of
      protection of less than 15 y could result in an older susceptible cohort and no
      decrease in cancer incidence. While vaccination has the potential to
      significantly reduce type-specific cancer incidence, its combination with
      screening further improves cancer prevention. CONCLUSIONS: HPV vaccination has
      the potential to significantly decrease HPV type-specific cervical cancer
      incidence. High vaccine coverage of women alone, sustained over many decades,
      with a long duration of vaccine-conferred protection, would have the greatest
      impact on type-specific cancer incidence. This level of coverage could be
      achieved through national coordinated programmes, with surveillance to detect
      cancers caused by nonvaccine oncogenic HPV types.

PMID- 16573365
TI  - Potential impact of intermittent preventive treatment (IPT) on spread of drug
      resistant malaria.
AB  - BACKGROUND: Treatment of asymptomatic individuals, regardless of their malaria
      infection status, with regularly spaced therapeutic doses of antimalarial drugs
      has been proposed as a method for reducing malaria morbidity and mortality. This
      strategy, called intermittent preventive treatment (IPT), is currently employed
      for pregnant women and is being studied for infants (IPTi) as well. As with any
      drug-based intervention strategy, it is important to understand how
      implementation may affect the spread of drug-resistant parasites. This is a
      difficult issue to address experimentally because of the limited size and
      duration of IPTi trials as well as the intractability of distinguishing the
      spread of resistance due to conventional treatment of malaria episodes versus
      that due to IPTi when the same drug is used in both contexts. METHODS AND
      FINDINGS: Using a mathematical model, we evaluated the possible impact of
      treating individuals with antimalarial drugs at regular intervals regardless of
      their infection status. We translated individual treatment strategies and drug
      pharmacokinetics into parasite population dynamic effects and show that immunity,
      treatment rate, drug decay kinetics, and presumptive treatment rate are important
      factors in the spread of drug-resistant parasites. Our model predicts that
      partially resistant parasites are more likely to spread in low-transmission
      areas, but fully resistant parasites are more likely to spread under conditions
      of high transmission, which is consistent with some epidemiological observations.
      We were also able to distinguish between spread of resistance due to treatment of
      symptomatic infections and that due to IPTi. We showed that IPTi could accelerate
      the spread of resistant parasites, but this effect was only likely to be
      significant in areas of low or unstable transmission. CONCLUSIONS: The results
      presented here demonstrate the importance of considering both the half-life of a
      drug and the existing level of resistance when choosing a drug for IPTi. Drugs to
      which little or no resistance exists are not advisable for IPT in high
      transmission areas, but IPTi is not likely to significantly impact the spread of
      highly resistant parasites in areas where partial resistance is already
      established. IPTi is more likely to accelerate the spread of resistance in high
      transmission areas than is IPT in adults (i.e., pregnant women).

PMID- 16573366
TI  - Cluster clinics for migrant Hispanic farmworkers with diabetes: perceptions,
      successes, and challenges.
AB  - INTRODUCTION: Diabetes is a chronic disease that requires individuals to schedule
      multiple office visits with a multidisciplinary team to learn how to successfully
      manage and delay the progression of complications. To respond to the health-care
      and educational needs of Hispanic migrant farmworkers who travel to Minnesota and
      North Dakota, the Migrant Health Service Inc diabetes program coordinator
      implemented evening cluster clinics. The purpose of this research project was to
      describe Hispanic migrant farmworkers' perceptions of the services provided to
      them at 37 multidisciplinary cluster clinics designed to serve this rural
      population diagnosed with diabetes. METHODS: This descriptive research employed a
      questionnaire and individual interviews. Both quantitative and qualitative data
      were obtained from cluster clinic clients. Quantitative data consisted of the
      numbers and percentages of clients providing various responses to questionnaire
      items. The qualitative data consisted of the verbal responses of clients to two
      open-ended questionnaire items and to an interview protocol. RESULTS: The main
      findings of the project indicated that 75-88% of the clients rated the services
      provided at the 37 cluster clinics as 'excellent'; an additional 21-25% rated
      them as 'good.' More than 85% of the clients indicated either that 'nothing
      should be changed' (59%) or that 'everything was fine' (26%). These ratings and
      content analysis of the interview data revealed that the clients perceived they
      had received quality services at these cluster clinics. The authors also discuss
      six characteristics that they believed contributed to the successful delivery of
      health care and education through cluster clinics. These characteristics include:
      (1) provision of both direct and referral services for this underserved
      population; (2) comprehensive delivery of services in a single setting; (3)
      collaborative delivery of services; (4) access-driven delivery of services; (5)
      delivery of culturally-sensitive and linguistically-appropriate services; and (6)
      evidence-based service delivery. CONCLUSIONS: Cluster clinics are an effective
      way to improve health-care services, education, and counseling for the under
      served or unserved Hispanic migrant population diagnosed with diabetes. The
      authors conclude with four primary challenges to the implementation of these
      cluster clinics which include: (1) locating and preparing facilities; (2)
      recruiting health-care providers for the clinics; (3) achieving effective,
      appropriate communication with clients; and (4) securing funding.

PMID- 16573367
TI  - New frontiers for cardiac risk assessment: C-reactive protein.
AB  - Current theories of atherosclerotic plaque formation suggest that inflammation
      plays a key role in coronary heart disease. In an effort to augment current tools
      for cardiac risk assessment, researchers have found that levels of the
      inflammatory marker C-reactive protein (CRP) may play an important role in
      gauging an individual's risk for a cardiac event. While not currently recommended
      for mass population screening, measurement of CRP may play an increasing part in
      identifying at-risk patients and guiding pharmacologic intervention.

PMID- 16573368
TI  - Biogenerics: potential benefits and obstacles.
AB  - Stakeholders in the prescription drug process are familiar with the savings
      possible when generic substitution is available. When drugs that enjoy a large
      market share come off patent, multiple generic manufacturers usually are ready to
      market a lower-cost generic. Today, the fastest growing segment of the
      pharmaceuticals market is biologics. Although the patents for several costly and
      successful biologics have expired or will expire in the near future, no
      biogenerics have yet been approved. The scientific difficulties of replicating
      large sugar- and protein-based molecules and related safety issues represent
      obstacles to an abbreviated biologics approval process.

PMID- 16573369
TI  - A review of the management of heart failure in long-term care residents.
AB  - OBJECTIVE: The objective of this study was to describe the characteristics of
      long-term care residents with heart failure (HF), to evaluate the management of
      HF, and to compare their management with nationally published American College of
      Cardiology/American Heart Association guidelines. DESIGN/SETTING: Residents in
      long-term care facilities were identified by diagnosis of HF within their
      electronic medical record. PARTICIPANTS: Data were collected on 302 residents in
      19 long-term care facilities. The average age of the study population was 83.2 +/
      11.1 years and comprised 68.5% females. RESULTS: Diabetes, obesity,
      hypertension, coronary artery disease, dementia, and hypothyroidism were
      identified in greater than 30% of residents. A diuretic was prescribed in 76.8%
      of residents. Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers
      were prescribed to 40.7% and 38.4% of residents, respectively; 16.2% of residents
      received both agents. Residents with diabetes or hypertension were not prescribed
      ACE inhibitors more often than residents without these comorbidities. Digoxin was
      prescribed more frequently in residents with atrial fibrillation (P = 0.028).
      Hospital admissions related to HF were documented in 30 (9.9%) residents within
      the past 12 months. CONCLUSIONS: According to guidelines, most patients with HF
      should be routinely managed with a combination of four types of drugs: a
      diuretic, an ACE inhibitor, a betablocker, and, often, digoxin. Improvement in HF
      outcomes resulting in reduced morbidity and mortality may be achieved through
      greater adherence to nationally recognized guidelines. Opportunities exist for
      health care professionals to improve the management of residents with HF through
      appropriate drug therapy management.

PMID- 16573370
TI  - Polypharmacy in a 75-year-old patient with schizoaffective disorder.
AB  - A 75-year-old white female with schizoaffective disorder was admitted to an
      inpatient psychiatry unit for uncooperativeness in refusing to take scheduled
      medications. She complained of anticholinergic adverse effects and had abnormal
      involuntary movements in the oral/buccal region. The patient had been prescribed
      six psychotropic medications (i.e., thiothixene, lithium, divalproex sodium,
      amitriptyline, benztropine, and trazodone effects. The treatment team determined
      that the patient was noncompliant and experienced the effects of polypharmacy.
      She had been prescribed two mood stabilizers and suffered from anticholinergic
      adverse effects and the movement disorder tardive dyskinesia (TD). Four
      medications were discontinued: thiothixene, amitriptyline, lithium, and
      benztropine. Quetiapine, a second-generation antipsychotic, was recommended, with
      a daily titration schedule to reach a target dose of 600 mg per day in divided
      doses. This agent has less propensity to cause movement disorders compared with
      first-generation antipsychotics. All medications with additive anticholinergic
      properties also were discontinued. Lithium was stopped secondary to
      subtherapeutic levels and potential drug interactions. The pharmacist educated
      the inpatient team on the additive anticholinergic effects of each medication,
      reduced the total number of medications prescribed, and assisted in appropriate
      conversion to quetiapine to reduce TD symptoms.

PMID- 16573371
TI  - Preparing case reports for publication: a guide for pharmacists.

PMID- 16573373
TI  - Relationship between plasma carotenoids and prostate cancer.
AB  - Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk,
      but the relationship between plasma carotenoid concentrations and risk in various
      populations has not been well characterized. Comparing 118 non-Hispanic Caucasian
      men mainly from southeast Texas with nonmetastatic prostate cancer with 52
      healthy men from the same area, we conducted a case-control analysis evaluating
      associations between risk and plasma levels of total carotenoids, beta
      cryptoxanthin, alpha- and trans-beta-carotene, lutein and zeaxanthin, total
      lycopenes, trans-lycopene, total cis-lycopenes, and cis-lycopene isoforms 1, 2,
      3, and 5. Risk for men with high plasma levels of alpha-carotene, trans-beta
      carotene, beta-cryptoxanthin, and lutein and zeaxanthin was less than half that
      for those with lower levels. In contrast, we observed no significant associations
      for total lycopenes, all-trans-lycopene, and cis-lycopene isomer peaks 2, 3, and
      5, although high levels of cis-lycopene isomer peak 1 were inversely associated
      with risk. Analysis of men with aggressive disease (Gleason scores of > or =7, n
      = 88) vs. less aggressive cases (Gleason scores of <7, n = 30) failed to reveal
      significant associations between carotenoid levels and the risk of diagnosis with
      aggressive disease. These findings suggest that, in these men, higher circulating
      levels of alpha-cryptoxanthin, alpha-carotene, trans-beta-carotene, and lutein
      and zeaxanthin may contribute to lower prostate cancer risk but not to disease
      progression.

PMID- 16573374
TI  - Fat from different foods show diverging relations with breast cancer risk in
      postmenopausal women.
AB  - The aim was to explore previous findings within the Malmo Diet and Cancer cohort
      (Sweden) that omega6-fatty acid intakes are positively associated with breast
      cancer risk among women 50 yr of age and older and specifically examine relations
      between breast cancer risk and fat from different food groups. Incident breast
      cancer cases (n = 237) were matched to controls (n = 673) on age and screening
      date. A modified diet history method, a structured questionnaire, and
      anthropometric measurements provided data. Fat-food variables from 24 food groups
      were computed. Conditional logistic regression examined breast cancer risk
      associated with energy-adjusted exposure categories of fat-food variables. Fat
      from fermented milk products was negatively associated with breast cancer risk
      (trend, P = 0.003). The highest quartiles of vegetable oil-based dietary fats
      (odds ratio, OR = 1.74; confidence interval, CI = 1.12-2.72) and dried soup
      powders (OR = 1.59; CI = 1.04-2.43) showed positive associations. Dietary fiber
      did not influence associations.

PMID- 16573375
TI  - Case-control analysis of dietary folate and risk of bladder cancer.
AB  - Dietary folate, a water-soluble B vitamin found in a variety of fruits and
      vegetables, is of particular interest as a chemopreventive agent due to its role
      in DNA methylation and DNA synthesis and repair. We hypothesized that individuals
      with low folate intake would be at an increased risk for bladder cancer. Using an
      ongoing case-control study we assessed dietary folate in 409 incident bladder
      cancer patients and 451 healthy control subjects. A food-frequency questionnaire
      was used to estimate naturally occurring food folate (microg/kcal/day), dietary
      folate equivalents (DFE) from food sources (microg DFE/kcal/day), and DFE from
      all sources (microg DFE/kcal/day). Unconditional logistic regression analyses
      were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
      Bladder cancer patients reported a statistically significant lower intake of
      folate than control subjects for food folate and DFE from food sources (P <
      0.001) but not for DFE from all sources (P = 0.061). In the highest quartile of
      food folate intake there was a 54% reduced risk for bladder cancer (OR = 0.46;
      95% CI = 0.29-0.73) after adjusting for age, gender, ethnicity, smoking, and
      total energy intake. Similarly, the highest quartile of intake was associated
      with a 59% reduced risk for DFE from food sources (OR = 0.41; 95% CI = 0.26-0.65)
      and a 35% reduced risk for DFE from all sources (OR = 0.65; 95% CI = 0.42-1.00).
      In the joint-effects analyses using never smokers with high folate intake as the
      reference group (OR = 1.0), heavy smokers with low food folate intake had a 2.31
      fold (95% CI = 1.11-4.82) increased risk, whereas heavy smokers with high folate
      intake had a reduced OR of 1.31 (95% CI = 0.53-3.26). Although the ORs were not
      statistically significant, light smokers and high folate intake exhibited a
      protective effect (OR = 0.62; 95% CI = 0.20-1.94), whereas an increased risk was
      observed for light smoking and low folate intake (OR = 1.41; 95% CI = 0.57-3.45).
      These patterns were consistent for the joint effects of smoking and DFE from food
      sources and DFE from all sources. In summary, high intake of dietary folate was
      associated with an overall decrease in bladder cancer risk. These data may have
      important implications for cancer prevention; however, large, hypothesis-driven,
      population-based clinical trials will be required to confirm these findings.

PMID- 16573376
TI  - Nutrition, lifestyle, and breast cancer risk among Turkish women.
AB  - Breast cancer is the most common malignancy in women, with more than 1 million
      cases occurring worldwide annually. Cancer is one of the leading causes of
      mortality in Turkey; deaths due to breast cancer constitute 24.1% of all
      carcinoma cases reported among women. We conducted a case-control study of
      Turkish women with and without breast cancer to investigate the relationships of
      selected lifestyle and nutritional risk factors with breast cancer risk. Factors
      were chosen based upon published associations with breast cancer. Subjects were
      women in Izmir, Turkey. Cases were 123 women with breast cancer registered with
      the Department of Oncology, Ege University Hospital, in February through July
      2004. The control group included 120 randomly selected women without a breast
      cancer diagnosis, registered with the Evka-4 Health Care Center and having
      similar sociodemographic characteristics. Inclusion criteria for participation
      consisted of 40 yr of age and over and willingness to participate. Chi2 tests and
      t-tests were used to determine statistical differences between cases and controls
      based on selected variables. Logistic regression was used to find the association
      between selected risk factors and breast cancer occurrence. Cases had smoked for
      more years, their age of first pregnancy was higher, and breast cancer occurrence
      was more common in first-degree relatives such as mothers and sisters of cases
      compared with controls. Cases were found to have consumed higher amounts of
      vegetable oil in contrast to controls. These findings are consistent with similar
      studies conducted in both developed and developing countries.

PMID- 16573378
TI  - Obstruction in patients with colorectal cancer increases morbidity and mortality
      in association with altered nutritional status.
AB  - Intestinal obstruction aggravates the prognosis of colorectal cancer (CRC)
      patients. The aim of this study was to carry out a comparative analysis of
      nutritional status and inflammatory response in CRC patients with or without
      intestinal obstruction. The study was carried out on 43 patients with CRC. Twenty
      three of these patients had intestinal obstruction. Anthropometric measurements,
      serum protein content, acute phase reactants, and diagnostic and risk nutritional
      indices were analyzed. The presence of intestinal obstruction reduced albumin (31
      +/- 5.2 vs. 36 +/- 4.2 g/l; P = 0.0025) and prealbumin (0.13 +/- 0.047 vs. 0.21
      +/- 0.042 g/l; P = 0.0001) and increased C-reactive protein (49 +/- 43.8 vs. 14
      +/- 16.7 mg/l; P = 0.006) and alpha1-antitrypsin (189 +/- 34.7 vs. 148 +/- 35.4
      mg/dl; P = 0.0011). Intestinal obstruction was related to malnutrition (86% vs.
      33%; P = 0.019) and Mullen's prognostic nutritional index (48 +/- 21.7 vs. 31 +/-
      17.9; P = 0.038) in CRC patients. Mullen's nutritional risk index was inversely
      correlated to total cholesterol (r = -0.51; P = 0.0002) and albumin (r = -0.81; P
      = 0.0001). No correlation was found between Duke's tumor stages and acute phase
      response, inflammatory parameters, and malnutrition. In conclusion, intestinal
      obstruction occurred more frequently in CRC patients with malnutrition. The
      increased morbidity and mortality of CRC patients was also associated with acute
      phase response, inflammation, and low serum cholesterol and triglyceride
      concentration.

PMID- 16573377
TI  - Effects of a 3-mo consumption of short-chain fructo-oligosaccharides on
      parameters of colorectal carcinogenesis in patients with or without small or
      large colorectal adenomas.
AB  - Intervention studies of colorectal adenoma recurrence have demonstrated the need
      for surrogate markers of the cancer risk. Short-chain fructo-oligosaccharides (sc
      FOS) have protective actions on colon carcinogenesis in animal models. We
      investigated differences in biological markers between adenoma and adenoma-free
      subjects, before and after 3 mo of daily intake of 10 g sc-FOS, within a
      multicenter study. After a full colonoscopy, 3 groups were studied at baseline
      and after 3 mo: 26 subjects with small colorectal adenoma(s), 18 with large
      adenoma(s), and 30 with no adenoma. At baseline, the mean fecal butyrate
      concentration was significantly lower in the adenoma groups than in the adenoma
      free group (12.01 +/- 5.08 vs. 17.28 +/- 7.34 mmol/g dry weight) but was
      significantly increased in that group after 3-mo ingestion of sc-FOS (15.7 +/-
      8.0 mmol/g; P = 0.02). In subjects without adenoma, sc-FOS ingestion was
      associated with a decrease in fecal lithocholic acid (P = 0.02) and an increase
      in cholic acid (P = 0.02), chenodeoxycholic acid (P = 0.04), total primary bile
      acids (P = 0.03), and ursodeoxycholic acid (P = 0.05). Fecal pH, blood
      parameters, and crypt cell proliferation were not significantly modified by sc
      FOS ingestion in either group. In subjects with and without adenoma, sc-FOS
      affects some aspects of the colonic environment, which may be involved in
      prevention of colorectal neoplasia.

PMID- 16573379
TI  - Chemo-immunotherapy of breast cancer using vesiculated alpha-tocopheryl succinate
      in combination with dendritic cell vaccination.
AB  - In this study, we evaluated the efficacy of vesiculated alpha-tocopheryl
      succinate (Valpha-TOS) in combination with non-antigen pulsed, nonmatured
      dendritic cells (nmDC) to treat pre-established tumors of the highly metastatic
      murine mammary cancer cell line 4T1. We demonstrated that Valpha-TOS in
      combination with non-antigen pulsed nmDC significantly inhibits the growth of
      established tumors in vivo and prolongs survival of treated mice. In addition,
      when initiated after resection of the established primary tumor, the combination
      treatment dramatically inhibits residual metastatic disease. The clinical
      response achieved with the combination therapy was correlated with increased
      interferon-gamma and interleukin-4 (IL-4) production by splenic lymphocytes and
      draining lymph node cells. Interestingly, when used in combination with Valpha
      TOS, nmDC were as effective as tumor necrosis factor-alpha matured DC at
      inhibiting the growth of pre-established tumors. Valpha-TOS-induced cellular
      factors collected by high-speed centrifugation of supernatant from Valpha-TOS
      treated tumor cells caused maturation of DC as evidenced by the up-regulation of
      co-stimulatory molecules and secretion of IL-12p70. These results demonstrate the
      potential usefulness of Valpha-TOS + DC chemo-immunotherapy in treating
      established primary mammary tumors as well as residual metastatic disease.

PMID- 16573380
TI  - Ratio of n6 to n-3 fatty acids in the diet affects tumor growth and cachexia in
      Walker 256 tumor-bearing rats.
AB  - In this study we investigate the impact of the dietary ratio of n-6 to n-3 fatty
      acids (FAs) from postweaning until adult age upon tumor growth, lipid
      peroxidation in tumor tissue, and metabolic indicators of cancer cachexia in
      Walker 256 tumor-bearing rats. Weanling male Wistar rats received a normal low
      fat (40 g/kg diet) chow diet or high-fat diets (300 g/kg) that included fish oil
      (FO) or sunflower oil or blends of FO and sunflower oil to yield n-6 to n-3 FA
      ratios of approximately 6:1, 30:1, and 60:1 ad libitum. After 8 wk, half of each
      group was inoculated with 1 ml of 2 x 10(7) Walker 256 cells. At the 14th day
      after tumor inoculation, the animals were killed, and tumors and blood were
      removed. The different diets did not modify the blood parameters in the absence
      of tumor bearing, except the high-FO diet, which decreased serum cholesterol and
      triacylglycerol concentrations. Tumor weight in chow-fed rats was 19 g, and these
      rats displayed cancer cachexia, characterized by hypoglycemia, hyperlacticidemia,
      hypertriacylglycerolemia, loss of body weight, and food intake reduction. Tumor
      weight in FO-fed rats was 7.7 g, and these animals gained body weight (14.6 g)
      and maintained blood metabolic parameters similar to non-tumor-bearing animals.
      Tumor weight in rats fed the diet with an n-6 to n-3 FA ratio of 6:1 was similar
      to tumor-bearing, chow-fed rats, but they gained 2 g in the body weight and blood
      metabolic parameters were similar to those in non-tumor-bearing rats. However, a
      further increase in the n-6 FA content of the diet did not change the cachectic
      state associated with tumor bearing. In this experimental model, a dietary n-6 to
      n-3 FA ratio of 6:1 was able to increase food intake and body weight, restore the
      biochemical blood parameters of cachexia, and prevent the development of cancer
      cachexia.

PMID- 16573381
TI  - Effect of high dose of pyridoxine on mammary tumorigenesis.
AB  - The effect of high-dose pyridoxine (PN) on mammary tumorigenesis was examined in
      female Sprague-Dawley rats. The first mammary tumors appeared between 84 and 90
      days after 7,12-dimethylbenzanthracene treatment. There was no effect of PN level
      on tumor incidence at 90 days but at 98, 104, and 111 days. Tumor incidence was
      lower in the high-dose group (35 mg PN/kg diet) compared with the controls (7 mg
      PN/kg diet). All tumors were identified as adenocarcinoma and most as papillary
      type. The number of microcarcinomas in mammary glands of the 35-mg PN group
      tended to be reduce than that of the 7-mg group. The number of proliferating Ki67
      positive cells was significantly reduced by supplementation with PN.

PMID- 16573382
TI  - Effect of bile acids on butyrate-sensitive and -resistant human colon
      adenocarcinoma cells.
AB  - A controlled balance among cell proliferation, differentiation, and apoptosis is
      required for the maintenance of gastrointestinal mucosa; these processes are
      influenced by luminal components, such as butyrate and bile acids. Using butyrate
      sensitive (BCS-TC2) and butyrate-resistant (BCS-TC2.BR2) human colon carcinoma
      cells, we wanted to establish whether colon carcinoma cells that acquire
      resistance to butyrate-induced apoptosis are also resistant to the cytotoxic
      effect of certain bile acids, contributing, in this way, to the progression of
      colon carcinogenesis. The effect of bile acids on BCS-TC2 cell viability is dose
      and time dependent and highly stereospecific. Quantification of the relative
      percentage of apoptotic cells and caspase-3 activity reveals that deoxycholic
      acid (DCA) and chenodeoxycholic acid (CDCA) induce apoptosis in BCS-TC2 cells.
      BCS-TC2.BR2 cells are consistently less sensitive to their cytotoxic effects,
      requiring concentrations to induce 50% inhibition (IC50) in cell viability of 740
      microM and >1 mM for CDCA and DCA, respectively, compared with IC50 values of 310
      and 540 microM for BCS-TC2 cells. DCA-treated BCS-TC2.BR2 cells show few
      apoptotic signs and no caspase-3 activation. On the other hand, CDCA-treated BCS
      TC2.BR2 cells show caspase-3 activation and apoptotic features, although to a
      lower extent than BCS-TC2 cells. Our results, in an in vitro model system, point
      out that acquisition of butyrate resistance is accompanied by a partial
      resistance to the cytotoxic effects of bile acids, which may enhance the survival
      of tumorigenic cells.

PMID- 16573383
TI  - Quercetin induces necrosis and apoptosis in SCC-9 oral cancer cells.
AB  - Evidence has accumulated that dietary polyphenols, in particular, flavonoids,
      have protective effects against oral cancer. In this study, we have examined the
      effects of quercetin, a major dietary flavonoid, on cell growth and
      necrosis/apoptosis and cell cycle regulation in human oral squamous carcinoma SCC
      9 cells. Quercetin induced dose- and time-dependent, irreversible inhibition of
      cell growth and cellular DNA synthesis. Light microscopy and lactate
      dehydrogenase measurements showed modifications in the morphology and membrane
      integrity of these cells after quercetin treatment. Propidium iodide/annexin V
      staining showed that quercetin induced necrosis at 24 h and 48 h, whereas at 72 h
      cells underwent apoptosis, correlating with caspase-3 activation. Flow cytometry
      studies of the cell cycle distribution showed that quercetin induced mainly S
      phase arrest. Thymidylate synthase (TS), a key S-phase enzyme, was inhibited in a
      time- and dose-dependent fashion by quercetin at the protein level. A lack of
      effect on TS mRNA suggested that TS down-regulation occurred at the translational
      level. In conclusion, our data support a view that quercetin initially induces a
      stress response, resulting in necrosis of these oral epithelial cells. Prolonged
      exposure of the surviving cells to quercetin causes apoptosis, presumably
      mediated by inhibition of TS protein.

PMID- 16573384
TI  - Cyanidin 3-glucoside and peonidin 3-glucoside inhibit tumor cell growth and
      induce apoptosis in vitro and suppress tumor growth in vivo.
AB  - Dietary polyphenols, including anthocyanins, are suggested to be involved in the
      protective effects of fruits and vegetables against cancer. However, anticancer
      effects of peonidin 3-glucoside have not been clearly demonstrated, with only
      limited studies being available concerning the inhibitory effect of cyanidin 3
      glucoside for tumor cell growth. Therefore, in this study, we have isolated and
      identified the two bioactive compounds, peonidin 3-glucoside and cyanidin 3
      glucoside, from Oryza sativa L. indica, to treat various cancer cells. The
      results showed that, among analyzed cell lines, HS578T was the most sensitive to
      peonidin 3-glucoside and cyanidin 3-glucoside. Treatment with peonidin 3
      glucoside or cyanidin 3-glucoside resulted in a strong inhibitory effect on cell
      growth via G2/M arrest. Regarding cell cyclerelated proteins, peonidin 3
      glucoside treatment resulted in down-regulation of protein levels of cyclin
      dependent kinase (CDK)-1, CDK-2, cyclin B1, and cyclin E, whereas cyanidin 3
      glucoside could decrease the protein levels of CDK-1, CDK-2, cyclin B1, and
      cyclin D1. In addition, cyanidin 3-glucoside or peonidin 3-glucoside also induced
      caspase-3 activation, chromatin condensation, and cell death. Furthermore,
      anthocyanins from O. sativa L. indica were evidenced by their inhibition on the
      growth of Lewis lung carcinoma cells in vivo.

PMID- 16573385
TI  - Quality assessment of commercial dietary antioxidant products from Vitis vinifera
      L. grape seeds.
AB  - Phenolic preparations from Vitis vinifera L. grape seeds are products commonly
      used in the formulation of dietary antioxidant supplements. In this article, we
      used a methodology (the oxygen radical absorbance capacity, ORAC) to evaluate the
      in vitro antioxidant capacity of commercial dietary grape seed products and
      studied the relationship of the antioxidant capacity with the phenolic
      composition of these products. The ORAC value of the different brands of
      commercial products studied (n = 16) varied from 2.71 to 26.4 micromol Trolox
      equivalents/mg (approximately equal to 10-fold difference). For four of these
      products, the batch-to-batch ORAC variation, expressed as a coefficient of
      variation of the mean, was 10.5% (n = 6), 13.1% (n = 3), 19.4% (n = 4), and 7.8%
      (n = 4). Analysis of monomeric and oligomeric flavan-3-ols by liquid
      chromatography-diode array detection (LC-DAD)/electrospray-mass spectrometry and
      procyanidins by thiolysis-LC-DAD also revealed large differences among the
      commercial grape seed products. Moreover, the ORAC value could be fitted to a
      regression model using variables from contents of individual phenolic compounds
      and procyanidins. The product-to-product and batch-to-batch variation in ORAC
      values and flavan-3-ol composition found among the commercial products studied
      demonstrated that they are poorly standardized, resulting in inconsistent
      composition and biological activity.

PMID- 16573393
TI  - Coping with oxidative stress.

PMID- 16573394
TI  - Supraventricular tachycardia classification: an intensivist's perspective.

PMID- 16573395
TI  - Consent for the critically ill patient.

PMID- 16573396
TI  - L-lactic acidosis: not just an hypoxic disorder.

PMID- 16573397
TI  - Early enteral nutrition support improves outcome: hypothesis or fact?

PMID- 16573398
TI  - Coagulation profiles in neonates--if the specimen clots repeat the test.
AB  - OBJECTIVE: The aims of this study were to determine in two institutions the
      frequency of clotted coagulation profile specimens in neonatal patients, the
      proportion of patients who had the test repeated if the coagulation profile
      specimen clotted and the number of abnormal results in the tests that were
      repeated. METHODS: The number of neonatal coagulation profiles (i.e. prothrombin
      time and activated partial thromboplastin time) were identified from the
      pathology databases at the Royal Women's Hospital and at the Mater Mother's
      Hospital. Each specimen that clotted and the number of tests that were repeated
      were identified and counted. Data from the tests that were repeated were analysed
      and compared with normal ranges for neonates. RESULTS: There were 746 specimens
      that were sent for a coagulation profile of which 45 (6.0%) clotted. Of the 45
      clotted specimens, 31 (69%) were repeated. From the 31 repeated specimens, 6
      clotted, 1 was an 'insufficient' specimen, and 24 were able to be processed. From
      the 24 processed specimens 17 (71%) had an abnormal result, 11 of which had a
      mildly elevated prothrombin time and the other six had a severe clotting
      abnormality. CONCLUSIONS: If a neonatal patient's coagulation profile specimen
      clots it should not be assumed that the infant's clotting is normal, and another
      specimen should be sent for analysis.

PMID- 16573399
TI  - The use of N-acetylcysteine in intensive care.
AB  - OBJECTIVE: To review the actions and clinical use of serum N-acetylcysteine in
      the critically ill patient. DATA SOURCES: A review of articles published on the
      mechanisms of action and clinical use of N-acetylcysteine. SUMMARY OF REVIEW: N
      acetylcysteine (NAC) is an amino acid with a MW of 163.2. It acts as an
      antioxidant, both directly as a glutathione substitute and indirectly as a
      precursor for glutathione. It also causes vasodilation by increasing cyclic
      guanosine monophosphate levels, inhibits platelet aggregation, acts as a
      sulphydryl donor to regenerate endothelial-derived relaxing factor and reduces IL
      8 and TNF-alpha production. While there is evidence for its effectiveness as an
      antidote to paracetamol poisoning, its use in other disorders has only
      experimental or anecdotal support. For example, in hepatic failure, there are few
      studies in man showing improved outcome following NAC therapy. There is also
      conflicting evidence for the use of NAC in sepsis or ARDS and while there is some
      evidence to suggest that NAC may be of benefit in acute myocardial infarction,
      the patient numbers are small. It may also be of use in ameliorating nitrate
      tolerance. It is also possible that NAC may confer benefit in reducing the risks
      of radiographic contrast nephropathy, although the study suggesting this was
      probably insufficiently powered to review all patient subsets (e.g. diabetics). N
      acetylcysteine would also appear to enhance T cell function in HIV infected
      patients. However, the use of NAC for immunomodulation in HIV patients has not
      yet undergone prospective randomised controlled trials and therefore cannot be
      recommended as routine therapy in HIV infected, or other immune deficient,
      patients. There is currently insufficient evidence to propose NAC for the
      treatment of carbon monoxide poisoning. Whilst there is experimental evidence for
      a variety of novel roles for NAC, further clinical studies are required before it
      can be recommended for the routine management of any disorders other than that of
      paracetamol poisoning. CONCLUSIONS: N-acetylcysteine has antioxidant properties
      that may be useful in many clinical conditions. Currently, however, it can only
      be recommended as therapy for paracetamol poisoning, in all other disorders it is
      still under evaluation.

PMID- 16573400
TI  - Extracorporeal membrane oxygenation for Legionnaires disease: a case report.
AB  - A case of Legionella pneumonia, severe adult respiratory distress syndrome (ARDS)
      and multiple organ failure is described in a patient who required extracorporeal
      membrane oxygenation (ECMO) prior to transfer to a hospital with ECMO facilities.
      She eventually made a good recovery, highlighting the potential benefits of ECMO
      in patients with severe and refractory ARDS.

PMID- 16573401
TI  - Shoshin beri-beri precipitated by intravenous glucose.
AB  - A thiamine deficient patient presented to the emergency department with an acute
      confusional state, becoming unconscious and hypotensive following the
      administration of 32 g of intravenous glucose over 4 hr. A dramatic clinical
      improvement in his cardiovascular and neurological status followed a single intra
      venous dose of 250 mg of thiamine. Profound thiamine deficiency was confirmed on
      biochemical testing. A substantial proportion of hospital patients are thiamine
      deficient and intravenous dextrose may precipitate cardiovascular collapse and
      lactic acidosis due to the development of 'shoshin' beriberi. A rapid response to
      intravenous thiamine may confirm the diagnosis. All patients presenting with
      acute neurological dysfunction should receive thiamine before glucose-containing
      solutions are administered.

PMID- 16573402
TI  - Cardiac arrhythmias: diagnosis and management. The tachycardias.
AB  - OBJECTIVE: To review the diagnosis and management of cardiac arrhythmias in a two
      part presentation. DATA SOURCES: Articles and published peer-review abstracts on
      tachycardias and bradycardias. SUMMARY OF REVIEW: Normal cardiac rhythm
      originates from impulses generated within the sinus node. These impulses are
      conducted to the atrioventricular node where they are delayed before they are
      distributed to the ventricular myocardium via the His-Purkinje system.
      Abnormalities in cardiac rhythm are caused by disorders of impulse generation,
      conduction or a combination of the two and may be life threatening due to a
      reduction in cardiac output or myocardial oxygenation. Cardiac arrhythmias are
      commonly classified as tachycardias (supraventricular or ventricular) or
      bradycardias. The differentiation between supraventricular and ventricular
      tachycardias usually requires an assessment of atrial and ventricular rhythms and
      their relationship to each other. In the critically ill patient the commonest
      tachycardia is sinus tachycardia and treatment generally consist of management of
      the underlying disorder. Other supraventricular tachycardias (SVTs) include,
      atrial flutter, atrial fibrillation and paroxysmal supraventricular tachycardia
      (PSVT) all of which may require cardioversion, although to maintain sinus rhythm,
      antiarrhythmic therapy is often needed. Adenosine is useful in management and
      treatment many SVTs although its use in PSVT with Wolff-Parkinson-White syndrome
      is hazardous. Multifocal atrial tachycardia is a characteristic supraventricular
      tachycardia found in the critical ill patient. While it usually responds to
      intravenous magnesium sulphate, its management also requires removal of various
      precipitating factors. Ventricular tachycardia (VT) and ventricular fibrillation
      (VF) require urgent cardioversion and defibrillation respectively. Torsade de
      pointes should be differentiated from these ventricular arrhythmias as
      antiarrhythmic therapy may be contraindicated. CONCLUSIONS: Supraventricular and
      ventricular tachycardias in the critically ill patient often have underlying
      disorders that precipitate their development (e.g. hypokalaemia, hypomagnesaemia,
      anti-arrhythmic proarrhythmia, myocardial ischaemia, etc). While antiarrhythmic
      therapy and cardioversion or defibrillation may be required to achieve sinus
      rhythm, correction of the associated abnormalities is also required.

PMID- 16573403
TI  - Cardiac arrhythmias: diagnosis and management. The bradycardias.
AB  - OBJECTIVE: To review the diagnosis and management of cardiac arrhythmias in a two
      part presentation. DATA SOURCES: Articles and published peer-review abstracts on
      tachycardias and bradycardias. SUMMARY OF REVIEW: Bradycardias are caused by a
      failure of the sinus node to generate normal impulses or due to a defect in
      cardiac conduction that in turn causes a delay or failure of impulse propagation.
      During sleep, the heart rate may decrease to 30 beats per minute (bpm) with
      episodes of sinoatrial block, junctional rhythms and first and second degree
      atrioventricular block that occur often enough (particularly in trained athletes)
      to be considered normal variants. However, treatment is required if symptoms of
      dizziness, confusion, fatigue Stokes-Adams attacks or heart failure occur. Sinus
      node dysfunction or 'sick sinus syndrome' is usually caused by intrinsic nodal
      disease and may present with episodes of tachycardia and bradycardia (tachycardia
      bradycardia syndrome). Treatment usually requires a permanent pacemaker.
      Atrioventricular (AV) conduction disturbances are characterised by a delay or
      failure of the atrial impulse to be conducted through the AV conducting system.
      If the escape rhythm is unstable the patient also requires a pacemaker. In the
      critically ill patient tachycardias are more often encountered than bradycardias.
      However, the intensivist should be familiar and skilled in the management of
      complete heart block and asystole, correcting the underlying defect (drug
      toxicity, hyperkalaemia, etc), while using catecholamines, atropine aminophylline
      and a temporary pacemaker for initial resuscitation. CONCLUSIONS: Bradycardias
      are uncommon in the critically ill patient and often are caused by an underlying
      disorder (e.g. hyperkalaemia, calcium channel blocker toxicity, beta adrenergic
      receptor blocker toxicity, etc). However, post cardiac bypass and acute
      myocardial infarction may cause cardiac conduction defects that may require
      urgent resuscitation with a temporary pacemaker.

PMID- 16573404
TI  - Informed consent and the incompetent adult patient in intensive care--a New
      Zealand perspective.

PMID- 16573405
TI  - A 58 year old man with bleeding oesophageal varices who became hyponatraemic with
      renal replacement therapy.

PMID- 16573406
TI  - "...are you happy about that?".

PMID- 16573407
TI  - Dangerous manoeuvres?

PMID- 16573408
TI  - Does myoclonus following a cardiac arrest indicate a poor prognosis?

PMID- 16573410
TI  - Hypothermia as therapy in cerebral injury.

PMID- 16573409
TI  - Management of brown snake envenoming.

PMID- 16573411
TI  - Phosphate metabolism in intensive care patients with acute respiratory failure.
AB  - OBJECTIVE: To determine the variables predicting the change of plasma phosphate
      over the first 24 hr period in intensive care in patients with acute respiratory
      failure. METHODS: Fifty-seven patients were studied prospectively in a university
      teaching hospital intensive care unit (ICU). Thirty two patients were classified
      as having acute respiratory failure and a primary respiratory system diagnosis
      (group I), 10 were classified as having acute cardiogenic pulmonary oedema (group
      II) and 15 were general ICU patients (group III). Arterial blood specimens at
      intensive care unit admission (T0) and at 24 hr post-admission (T24) were assayed
      for multiple plasma biochemical parameters including phosphate (PO4) and red
      blood cell 2,3-diphosphoglycerate (2,3-DPG). Timed urine collections were used to
      determine 24 hr urine phosphate loss and renal phosphate threshold concentration
      (RTP). During the measurement period glucose-free fluids only were infused.
      RESULTS: Fifty seven patients had a mean (+/- SD) age of 67 +/- 12 years and
      Apache II score of 22 +/- 6. The plasma PO4 at T0 was 1.55 +/- 0.71 mmol/L and
      showed a significant 24 hr decrease of 0.55 mmol/L (p < 0.0001) at T24.
      Hypophosphataemia at T0 was observed in 26% of patients. Red blood cell 2,3-DPG
      was not elevated at T0 (13.5 +/- 3.3 umol/gHb) and showed a non-significant
      increment over 24 hr. Urine phosphate loss over the 24 hr period was 21.8 +/-
      14.0 mmol with RTP being reduced below the lower reference range limit in groups
      I (0.65 +/- 0.29 mmol/L) and II (0.57 +/- 0.29 mmol/L). The naive form of
      phosphate change (PO4T24-PO4T0) was significantly related to initial plasma PO4
      and was subject to regression to the mean, which was estimated to have inflated
      the relationship by 25%. The appropriate form of phosphate change was found to be
      log ratio T24/T0 phosphate. Independent predictors of log ratio T24/T0 phosphate
      were 24 hr change (T24-T0) in both 2,3-DPG and arterial pH, RTP, prescription of
      aminophylline (categorical factor) and the interaction of aminophylline and RTP
      (R2 = 0.65, ordinary least squares regression). CONCLUSIONS: Twenty-four hour
      plasma phosphate decrement in intensive care unit patients was multi-factorial
      and was attended by a lowered renal threshold phosphate concentration.

PMID- 16573412
TI  - Intention myoclonus in paediatric patients following severe cardiopulmonary
      failure: a report of three cases.
AB  - We describe the development of intention myoclonus following severe
      cardiopulmonary failure in three paediatric patients. Symptoms occurred during
      the withdrawal of midazolam and fentanyl, which were used for prolonged sedation,
      and resolved spontaneously. Because the three patients had concomitant brain
      injury secondary to cardiopulmonary failure.related hypoxia, we propose that the
      combination of hypoxic brain injury and sedative withdrawal may predispose to
      intention myoclonus.

PMID- 16573413
TI  - Potential dangers of the Valsalva maneuver and adenosine in paroxysmal
      supraventricular tachycardia--beware preexcitation.
AB  - Paroxysmal supraventricular tachycardia (PSVT) is a common clinical problem.
      Valsalva maneuver and adenosine are effective therapies for many patients with
      PSVT, although any conversion to an irregular or wide complex tachycardia should
      prompt consideration of a preexcitation syndrome. We report a case where the
      Valsalva maneuver and adenosine, in a patient with PSVT and previously
      undiagnosed Wolff-Parkinson-White syndrome, caused atrial fibrillation and led to
      a haemodynamically unstable wide complex tachycardia and ventricular
      fibrillation. In PSVT, where preexcitation has not been excluded, the Valsalva
      maneuver and adenosine can be potentially dangerous.

PMID- 16573414
TI  - Hepatic and renal failure associated with amiodarone infusion in a patient with
      hereditary fructose intolerance.
AB  - Hereditary fructose intolerance is a rare inherited metabolic disorder. Although
      fructose intolerance usually presents in the paediatric age group, individuals
      can survive into adulthood by self.manipulation of diet. Hospitalisation can
      become a high.risk environment for these individuals because of loss of control
      of their strict dietary constraints and the added danger of administration of
      medications containing fructose, sucrose and sorbitol. We report a case of
      hereditary fructose intolerance in an adult presenting with hepatic and renal
      failure associated with an amiodarone infusion and explore the possibility of
      polysorbate 80 as a cause of this patient's hepatic and renal failure.

PMID- 16573415
TI  - Early and late removal of the pressure bandage in brown snake envenomation: a
      report of two cases.
AB  - Two cases of brown snake envenomation are presented where the duration of bandage
      application in one patient was prolonged compared with the other patient and was
      associated with a reduction in the total amount of antivenom required. One
      patient had the bandage removed 2 hours and twenty minutes after application and
      required 25 units of brown snake antivenom to neutralise the defibrination
      coagulopathy and manage an upper gastrointestinal haemorrhage. This patient also
      sustained an urticarial reaction during administration of the final 5 vials of
      antivenom. The other patient had the bandage released more than 22 hours after
      its application and only required a total of 6 units of brown snake antivenom to
      neutralise the defibrination coagulopathy. In the latter case, there was no
      reaction to any of the vials of antivenom These cases suggest that bandage
      release could be delayed well beyond the usual recommended time to effect a
      reduction in peak and cumulative venom levels and antivenom requirements.

PMID- 16573416
TI  - Neurologic complications of critical illness: part I. Altered states of
      consciousness and metabolic encephalopathies.
AB  - OBJECTIVE: To review the metabolic encephalopathies and neuromuscular
      abnormalities commonly found in the critically ill patient in a two-part
      presentation. DATA SOURCES: A review of articles reported from 1980 to 2002 and
      identified through a MEDLINE search on metabolic encephalopathy, polyneuropathy
      and myopathy in critical illness. SUMMARY OF REVIEW: An alteration in the
      conscious state can be caused by space occupying lesions or infections of the
      central nervous system. However, in the critically ill patient a metabolic
      encephalopathy is often the cause of an acute confusional state or a reduced
      state of consciousness. There is no specific treatment for the metabolic
      encephalopathies as they commonly resolve when the underlying disorders (e.g.
      sepsis, renal failure, hepatic failure, electrolyte disturbance) are corrected.
      Management may also require judicious pharmacological and/or physical restraint
      in the case of the acute confusional states and ensuring an adequate airway,
      ventilation and circulation in the case of a reduced state of consciousness,
      while the underlying disorder is corrected and the encephalopathy resolves.
      CONCLUSIONS: In the critically ill patient a metabolic encephalopathy is commonly
      the cause of confusion, disorientation, agitation, drowsiness or coma. Sedative
      agents and tranquilisers may be required as well as management of the airway,
      ventilation and circulation while the underlying disorder is corrected to allow
      the encephalopathy to resolve.

PMID- 16573417
TI  - Neurologic complications of critical illness: part II. Polyneuropathies and
      myopathies.
AB  - OBJECTIVE: To review the metabolic encephalopathies and neuromuscular
      abnormalities commonly found in the critically ill patient in a two-part
      presentation. DATA SOURCES: A review of articles reported from 1980 to 2002 and
      identified through a MEDLINE search on metabolic encephalopathy, polyneuropathy
      and myopathy in critical illness. SUMMARY OF REVIEW: Severe weaknes in the
      critically ill patient may have many causes, although Guillain-Barre syndrome,
      critical illness polyneuropathy and critical illness myopathy are the motor
      disorders commonly found in the critically ill patient. Guillain-Barre syndrome
      is characterised by an acute ascending weakness 1-3 weeks after a
      gastrointestinal or upper respiratory tract infection. Intravenous immune
      globulin (or plasmapheresis) should be initiated as soon as possible to shorten
      the duration of ventilation, time to walk unaided and halt the progression of the
      disease. Critical illness polyneuropathy and critical illness myopathy often
      coexist in the critically ill patient and are probably caused by a small number
      of activated leucocytes that infiltrate skeletal muscle and produce pro and anti
      inflammatory cytokines. Axonal degeneration of both motor and sensory fibres with
      preservation of the myelin sheath cause the neuropathy, and muscle fibre necrosis
      and atrophy causes the myopathy. Apart from treatment of the underlying cause
      (e.g sepsis), there is no specific treatment, although a 44% reduction in the
      incidence of critical illness polyneuropathy has been described in mechanically
      ventilated critically ill patients who received intensive insulin therapy to
      maintain the blood glucose level between 4.4-6.1 mmol/L. Recovery usually occurs
      over weeks to months depending on the severity of the disease. CONCLUSIONS: An
      acute motor weaknesses in the critically ill patient may be caused by Guillain
      Barre syndrome, critical illness polyneuropathy or critical illness myopathy.
      Patients with severe Guillain-Barre syndrome should be managed in an intensive
      care unit and given intravenous immune globulin. Treatment of critical illness
      polyneuropathy or myopathy requires largely management of the underlying
      disorder.

PMID- 16573418
TI  - Doctors, economists and managers.

PMID- 16573420
TI  - "If you knew 20 years ago what ICU medicine would be like today, do you think
      that you would still choose to be an intensivist".

PMID- 16573419
TI  - A 17 year old woman with a six week history of anorexia, nausea and intermittent
      vomiting.

PMID- 16573421
TI  - Vasopressin--an old warhorse on a new campaign.

PMID- 16573422
TI  - What cardiovascular parameters should we aim for in the management of septic
      shock? (or are catecholamines being used to excess?).

PMID- 16573424
TI  - Nutrition as therapy: let's look at the evidence.

PMID- 16573423
TI  - Drug overdosage: a disorder that is now rarely managed in the tertiary hospital
      intensive care unit?

PMID- 16573425
TI  - Dynamic left ventricular outflow tract obstruction in critically ill patients.
AB  - OBJECTIVE: To review patients managed in an intensive care unit diagnosed with
      dynamic left ventricular outflow tract obstruction without hypertrophic
      cardiomyopathy. PATIENTS AND METHODS: Dynamic left ventricular outflow tract
      obstruction (DLVOTO) is characteristically associated with hypertrophic
      cardiomyopathy, although it has also been described in patients without this
      disorder. We reviewed patients managed in two intensive care units over a one
      year period who were hypotensive and/or resistant to catecholamine infusions.
      RESULTS: During the one year period nine critically ill patients were found on
      echocardiography to have DLVOTO. None of the patients had a prior history of
      hypertrophic cardiomyopathy (HOCM) or echocardiographic evidence of asymmetrical
      septal hypertrophy and in three patients HOCM was specifically excluded by prior
      or convalescent echocardiography or by post mortem analysis. We found the risk
      factors for DLVOTO included left ventricular hypertrophy, hypovolaemia and use of
      positive inotropic agents. All patients responded to an increase in intravascular
      volume, reduction in infused inotropic agents with one requiring metaraminol to
      maintain blood pressure. CONCLUSIONS: Dynamic left ventricular outflow tract
      obstruction without hypertrophic cardiomyopathy is not an uncommon cause of
      hypotension resistant to catecholamines in critically ill patients. The diagnosis
      is important because management which includes fluid loading, vasopressors and
      reducing catecholamine infusions, differs from the management of other causes of
      shock.

PMID- 16573426
TI  - Continuous veno-venous haemodiafiltration in sodium valproate overdose
      complicated by cerebral oedema: a case report.
AB  - A case of severe sodium valproate overdose is presented in which continuous
      venovenous haemodiafiltration was used. However, following the commencement of
      dialysis and a fall in the serum valproate levels, the patient developed cerebral
      oedema. This case demonstrated a poor correlation between serum valproate and its
      toxic effects and the lack of benefit of continuous venovenous haemodiafiltration
      in the management of sodium valproate overdose.

PMID- 16573427
TI  - Isolated fluvoxamine poisoning presenting with hypertonia and seizures: a case
      report.
AB  - Pharmacological management of depressed patients has often relied upon the use of
      agents that are toxic when taken in large quantities. The recent introduction of
      selective serotonin reuptake inhibitors (SSRIs) has represented a major advance
      in the management of depression. While a 'serotonin syndrome' may develop if
      these drugs are taken in association with other agents, these drugs are believed
      to have minimal toxicity when taken as an isolated overdose. A case of
      fluvoxamine poisoning presenting with hypertonicy and seizures is described,
      highlighting the fact that the SSRI's may not be harmless when taken in
      isolation, particularly when taken in large amounts.

PMID- 16573428
TI  - The physiology and clinical applications of vasopressin in critical illness.
AB  - OBJECTIVE: To present the physiology of vasopressin, and review published data on
      its use in critically ill patients. DATA SOURCES: A review of articles on the
      clinical use of vasopressin in critical care medicine up to 2002 and identified
      through a MEDLINE search. SUMMARY OF REVIEW: Vasopressin (antidiuretic hormone)
      acts via vasopressinergic receptors to maintain osmotic and baroreceptor
      homeostasis. It has complex and varying effects depending on serum levels,
      coexisting disease states and organs studied. Synthetic vasopressin is available
      for clinical use. In large doses (e.g. 40 U) it has vasoconstrictor effects
      comparable to epinephrine during cardiopulmonary resuscitation. The use of much
      lower "replacement" doses (e.g. 0.04 U/min) may have a marked vasopressor effect
      in clinical states associated with vasopressin deficiency; for example sepsis,
      the organ donor and after cardiopulmonary bypass. These doses are much lower than
      those leading to cardiovascular effects in healthy patients and may avoid the
      adverse vasoconstrictor effects seen at "pharmacological" doses. The use of
      vasopressin to reduce portal pressure and bleeding in oesophageal varices is well
      established. CONCLUSIONS: Vasopressin has widespread effects throughout the body
      and has several important clinical applications in the critically ill patient.

PMID- 16573429
TI  - Clinical toxicology: part I. Diagnosis and management of common drug overdosage.
AB  - OBJECTIVE: To review the diagnosis and management of drug overdosage in a two
      part presentation. DATA SOURCES: A review of articles reported on drug overdose
      and poisoning. SUMMARY OF REVIEW: A patient who has taken an overdose of a common
      drug often presents with an alteration in neurological, cardiovascular and
      respiratory functions. The differential diagnosis includes, central nervous
      system injury and metabolic encephalopathies (e.g. hepatic failure,
      hyponatraemia, hypocapnia, hypoglycaemia). In general, measures to prevent
      absorption (e.g. emesis, gastric lavage) or increase excretion (e.g. diuresis,
      catharsis) of the drug, have not been shown consistently to reduce mortality
      associated with drug toxicity. However, in selected instances adsorbents
      (activated charcoal, Fuller's earth), gastric lavage and haemodialysis or
      continuous renal replacement therapy are useful in the management of drug
      overdosage and specific antidotes can be recommended for individual poisons.
      Nevertheless, as the major hazards of an overdose are aspiration,
      hypoventilation, hypoxia, hypotension and cardiac arrhythmias, the most important
      aspects in the management of a poisoned patient is the maintenance of the
      patient's airway, ventilation and circulation, while the drug is excreted. The
      diagnosis and management of common drug overdoses (e.g sedative, hypnotic,
      psychoactive, neuroleptic, anticonvulsant, sympathomimetic, analgesic and cardiac
      drugs) as well as the alcohols are discussed in the first part of this
      presentation on clinical toxicology. CONCLUSIONS: In the critically ill overdosed
      patient, while activated charcoal, continuous renal replacement therapy and
      specific antidotes may be of benefit in selected cases, maintenance of the
      patient's airway, ventilation and circulation still remain the most important
      aspects of management.

PMID- 16573430
TI  - Clinical toxicology: part II. Diagnosis and management of uncommon poisonings.
AB  - OBJECTIVE: To review the diagnosis and management of drug overdose and poisonings
      in a two-part presentation. DATA SOURCES: A review of articles reported on drug
      overdose and poisonings. SUMMARY OF REVIEW: In patients who attempt suicide it is
      usual for the overdose to be a therapeutic agent, although in the severely
      mentally disturbed patient the agent may be an unusual poison. As with any
      overdose, the most important aspects in the management is the maintenance of the
      patient's airway, ventilation and circulation, while the toxin is metabolised and
      excreted. Adsorbents, gastric lavage and haemodialysis or continuous renal
      replacement therapy and specific antidotes may be beneficial in individual cases.
      The diagnosis and management of uncommon poisonings, including pesticides and
      herbicides (e.g. organophosphates, carbamates, paraquat, chlorophenoxy
      herbicides), carbon monoxide, cyanide, strychnine, halogenated hydrocarbons,
      elemental poisons (e.g. iron, arsenic, lead, mercury, selenium, barium, thallium,
      lithium, sodium, rubidium, cesium), alkaloids (e.g. mushroom, aconite, conium)
      and cantharidin poisoning along with the miscellaneous poisonings of quinine,
      chloroquine, isoniazid, thyroxine, cytotoxic agents (e.g. azothioprine, 6
      mercaptopurine, colchicine, methotrexate) are discussed in the second part of
      this presentation on clinical toxicology. CONCLUSIONS: In the critically ill
      patient who has taken an overdose of a non therapeutic agent, while activated
      charcoal, continuous renal replacement therapy and specific antidotes may be of
      benefit, maintenance of the patient's airway, ventilation and circulation still
      remain the most important aspects of management.

PMID- 16573431
TI  - Current privacy law governing the Australian health sector: implications for
      research and 'audit'.

PMID- 16573432
TI  - A 64 year old woman with a six hour history of confusion and weakness following
      bowel preparation for surgery.

PMID- 16573433
TI  - Everything old is new again.

PMID- 16573434
TI  - Therapeutic options for head injury in intensive care.

PMID- 16573435
TI  - Keeping continuous renal replacement therapy--continuous.

PMID- 16573436
TI  - Paediatric haemoglobin level: when should we worry?

PMID- 16573437
TI  - Learning new lessons or repeating old mistakes?

PMID- 16573438
TI  - Blood transfusion practice indicated by paediatric intensive care specialists in
      response to four clinical scenarios.
AB  - OBJECTIVE: Several clinical guidelines exist for blood transfusion in adults but
      only one refers to children. There are no guidelines for blood transfusion in
      critically ill children and the paediatric intensive care specialist's approach
      is unknown. We wished to evaluate the approach toward blood transfusion among a
      group of paediatric intensive care specialists. METHODS: All certified paediatric
      intensive care specialists from the Israeli society of pediatric intensive care
      medicine were requested to complete a questionnaire, which described four
      hypothetical common scenarios in paediatric intensive care units. In each case,
      the physicians were asked to denote the haemoglobin threshold at which they would
      prescribe a blood transfusion and the transfusion volume they would use. The
      specialists were also asked for their reasons for increasing their haemoglobin
      threshold for blood transfusion. RESULTS: The questionnaire was posted to twenty
      six paediatric intensive care specialists, twenty one of whom responded (i.e.
      80.8%). There was a wide variation for each scenario in both the suggested
      haemoglobin thresholds for transfusion (varying by 20-50 g/L) and the transfusion
      volume (varying by 10-20 mL/kg). The reasons given for increasing their blood
      transfusion threshold included, in order of importance, shock, haemodynamic
      instability and hypoxaemia. CONCLUSIONS: There is a marked variability among
      paediatric intensive care specialists regarding both the threshold haemoglobin
      level at which blood transfusion is prescribed as well as the volume used.

PMID- 16573439
TI  - The effect of circuit "down-time" on uraemic control during continuous veno
      venous haemofiltration.
AB  - OBJECTIVE: The term continuous veno-venous haemofiltration (CVVH) suggests a
      treatment without interruption. However, interruptions do occur and the duration
      of the haemofiltration circuit "down-time" may influence uraemic control. We
      conducted a prospective study to ascertain the percentage of operative "down
      time" for CVVH in our intensive care unit and to test the hypothesis that it
      significantly affected uraemic control. PATIENTS AND METHODS: Prospective data
      measuring the time spent off the filter in ten patients receiving CVVH were
      collected. Continuous veno-venous haemofiltration was performed at 2 litres per
      hour of ultrafiltration. Anticoagulation was maintained using unfractionated
      heparin administered pre-filter and infused at a rate to achieve a systemic APTT
      varying between 30-45 seconds. The circuit functional life was documented for
      each CVVH circuit as progressive cumulative hours of operation. The time off
      treatment was calculated for each 24-hour period. These data were then correlated
      with the change in plasma urea and creatinine concentrations for each 24-hour
      cycle. The APTT, INR, haemoglobin and platelet count were measured and levels
      were correlated with the filter duration. RESULTS: Ninety three days of CVVH
      treatment were assessed in 4 female and 6 male patients. The mean circuit "down
      time" in these patients for this period was 22% or 5.27 hours per day. The most
      common cause of circuit "down-time" was circuit clotting, followed by a need for
      radiological procedures, time spent in the operating theatre and catheter
      malfunction requiring replacement. There was a strong correlation between circuit
      "down-time" and increase in plasma urea (p = 0.0017) and creatinine (p = 0.0451)
      concentrations. Circuit "down-time" was also inversely correlated with the
      platelet count (p = 0.0048) but not significantly correlated with the APTT, INR
      or haemoglobin values. CONCLUSIONS: In our study the average daily duration of an
      interruption in CVVH (i.e. circuit "down-time") represented > 20% of the
      potential operative time. There was a strong correlation between time without
      treatment and solute control during CVVH. The percentage of "down-time" may be a
      useful marker of operative quality during CVVH.

PMID- 16573440
TI  - Indomethacin--a review of its role in the management of traumatic brain injury.
AB  - OBJECTIVE: To review the use of indomethacin in the management of traumatic brain
      injury. DATA SOURCES: Articles reported from 1966 to 2001 and identified through
      a MEDLINE search of the English language literature on the use of indomethacin in
      traumatic brain injury. SUMMARY OF REVIEW: Traumatic brain injury (TBI) is a
      frequent cause of mortality and morbidity in patients with head injury. The use
      of indomethacin in treating raised intracranial pressure (ICP) secondary to TBI
      is controversial. Clinical studies suggest that it may be useful in the
      management of intracranial hypertension, when used in combination with standard
      techniques, by decreasing cerebral blood flow and reducing ICP during the
      restoration of the blood brain barrier. Its unique mechanism of action may be due
      to precapillary vasoconstriction, which reduces the transcapillary transfer of
      fluid into the cerebral extracellular space. However, large, prospective,
      randomised and controlled studies have not yet been performed to confirm its
      benefit in patients with TBI. CONCLUSIONS: Indomethacin should only be considered
      as an experimental therapy for refractory intracranial hypertension in TBI
      patients, as current evidence is not available to support its routine use in the
      management of an elevated ICP. Its use in patients with cerebral vasospasm, renal
      failure, bleeding disorders, peptic ulceration and coagulopathies is
      contraindicated.

PMID- 16573441
TI  - Prolonged intermittent renal replacement therapy in the intensive care unit.
AB  - OBJECTIVE: To present a review on the use of prolonged intermittent renal
      replacement therapy in the intensive care patient. DATA SOURCES: Articles and
      abstracts reporting the use of renal replacement therapy. SUMMARY OF REVIEW:
      Standard intermittent haemodialysis (IHD) has significant shortcomings in the
      treatment of the acute renal failure (ARF) of critical illness. These
      shortcomings include haemodynamic instability, the need to remove excess fluid
      over a short period of time, the episodic nature of small solute control, the
      limited ability to achieve middle molecular weight solute control and the
      episodic nature of acid-base control. Over the last 20 years, these limitations
      have stimulated the evolution and increased application of continuous renal
      replacement therapy (CRRT) which provides major biochemical, biological and
      physiological advantages compared with IHD, although it remains unclear as to
      whether such advantages translate into a survival advantage. However, CRRT is
      technically demanding, requires supervision 24 hr per day and is often associated
      with the need for continuous anticoagulation, which, in some patients, might be
      undesirable. In some institutions, CRRT changes the nurse to patient ratio from
      1:2 to 1:1, an alteration which has cost implications and might affect resource
      availability for other patients. Accordingly, techniques which prolong the
      duration of intermittent therapy and avoid the need for 24 hr treatment may offer
      "best value" in the management of ARF in the intensive care unit (ICU). These
      techniques will be referred to as prolonged intermittent renal replacement
      therapies (PIRRT) in this article. They are characterised by several fundamental
      principles: 1. Use of a modified or standard dialysis machines, 2. Use of
      diffusion, convection or any combination of the two, 3. Application of a
      decreased intensity of solute removal compared with IHD, 4. Extended duration of
      treatment beyond the typical 3 or 4 hr of standard IHD (hence the term prolonged)
      but not beyond an 8-12 hr period (hence the term intermittent) and 5. Use of "on
      line" generation of dialysate or replacement fluid from tap water. CONCLUSIONS:
      Information is now being obtained on the efficacy and safety of PIRRT in the ICU.
      Several units in Australia have started applying this technology to patient care.
      It is now important that critical care physicians and nurses become familiar with
      its principles and practice.

PMID- 16573442
TI  - Monitoring tissue gas tensions in critical illness.
AB  - OBJECTIVE: To review the technology and the role of monitoring tissue oxygenation
      in critical illness. DATA SOURCES: Articles and published peer review abstracts
      on monitoring tissue oxygenation. SUMMARY OF REVIEW: Miniaturised optodes and
      electrode systems are the commonly used technology for measurement of tissue gas
      tensions. Reductions in tissue perfusion frequently leads to a decrease in tissue
      PO2 and an increase in tissue PCO2 which has been confirmed in a number of animal
      and human trials in hypovolaemic shock. Monitoring tissue oxygenation has also
      enabled the delineation of cytopathic hypoxia, which is one of the important
      pathophysiological mechanisms of sepsis. Although these devices have improved our
      understanding of pathophysiological mechanisms of critical illness, at a clinical
      level titrating oxygen therapy to tissue oxygen tensions has only been shown to
      be useful in patients with impaired wound healing. A number of questions remain
      unanswered in relation to the monitoring of tissue oxygenation in critical
      illness. These include establishing normal values of PO2 and PCO2 in humans at
      the various tissue beds, establishing dysoxic thresholds for the various tissues,
      identifying optimal sites for monitoring and improving measurement accuracy.
      Furthermore, the nature of microcirculatory blood flow and tissue gas exchange in
      critical illness is complex and incompletely understood, limiting our ability to
      interpret changes from the baseline. Knowing critical tissue PO2 thresholds will
      provide the clinician with practical resuscitation endpoints in hypoxia and
      shock, and may even modify the practice of 'permissive hypoxia' in severe
      respiratory failure. These questions need answers in the years to come.
      CONCLUSIONS: Monitoring of tissue oxygenation is largely a research tool. For its
      application in the critically ill patient there needs to be a greater
      understanding of normal values of PO2 and PCO2 at the various tissue beds,
      dysoxic thresholds for the various tissues and optimal sites for monitoring.

PMID- 16573443
TI  - The essentials of calcium, magnesium and phosphate metabolism: part I.
      Physiology.
AB  - OBJECTIVE: To review the components of calcium, phosphate and magnesium
      metabolism that are relevant to the critically ill patient in a two-part
      presentation. DATA SOURCES: A review of articles reported on calcium, phosphate
      and magnesium disorders in the critically ill patient. SUMMARY OF REVIEW:
      Calcium, phosphate and magnesium have important intracellular and extracellular
      functions with their metabolism often linked through common hormonal signals. A
      predominant portion of total body calcium is unionised within bone and serves an
      important structural function. Intracellular and extracellular ionised calcium
      changes are often linked and have important secretory and excitatory roles. The
      extracellular ionised calcium is carefully regulated by parathyroid hormone and
      vitamin D, whereas calcitonin is secreted largely in response to hypercalcaemia.
      Phosphorous is needed for bone structure although it also has an important role
      in cell wall structure, energy storage as ATP, oxygen transport and acid-base
      balance. Ionised calcium, in as far as it controls PTH secretion, indirectly
      controls urinary phosphate excretion. When plasma phosphate increases, tubular
      reabsorption also increases up to a maximum (TmPO4), thereafter phosphate is
      excreted. The minimum oral requirement for phosphate is about 20 mmol/day.
      Magnesium is a predominantly intracellular ion that acts as a metallo-coenzyme in
      more than 300 phosphate transfer reactions and thus has a critical role in the
      transfer, storage and utilisation of energy within the body. Extracellular
      magnesium concentrations are largely controlled by the kidneys with the renal
      tubular maximum reabsorption (TmMg) controlling the plasma magnesium
      concentration. CONCLUSIONS: In the critically ill patient calcium, magnesium and
      phosphate metabolism, are often disturbed with an alteration in intake, increased
      liberation from bone and damaged tissue and reduced excretion (e.g. during renal
      failure), causing alterations in extracellular concentrations and subsequent
      disordered organ function.

PMID- 16573444
TI  - The essentials of calcium, magnesium and phosphate metabolism: part II.
      Disorders.
AB  - OBJECTIVE: To review the components of calcium, phosphate and magnesium
      metabolism that are relevant to the critically ill patient, in a two-part
      presentation. DATA SOURCES: A review of articles reported on calcium, phosphate
      and magnesium disorders in the critically ill patient. SUMMARY OF REVIEW:
      Abnormal calcium metabolism in the critically ill patient often presents with an
      alteration in plasma ionised calcium. The characteristic clinical features of an
      acute reduction in ionised plasma calcium include tetany, laryngospasm,
      paraesthesia, confusion, hallucinations, seizures and, rarely, hypotension all of
      which resolve with intravenous calcium administration. The clinical features of
      an acute increase in plasma ionised calcium include anorexia, nausea, vomiting,
      constipation, polyuria, weakness, lethargy, hypotonia and ectopic calcification
      and, depending on the aetiology, may require intravenous saline, frusemide,
      diphosphonate, glucocorticoid or calcitonin. Acute hypophosphataemia may present
      with paraesthasia, confusion, seizures, weakness, hypotension and heart failure
      and in the critically ill requires intravenous sodium or potassium phosphate.
      Hyperphosphataemia is often associated with renal failure and if severe usually
      presents with the clinical features of the associated hypocalcaemia. The clinical
      features of hypomagnesaemia include confusion, delerium, seizures, weakness,
      cramps, tetany and tachyarrhythmias, all of which resolve with intravenous
      magnesium sulphate. Hypermagnesaemia is usually associated with excess magnesium
      administration in a patient with renal failure and if severe can cause areflexia,
      hypotonia, respiratory and cardiac arrest. Intravenous calcium chloride will
      rapidly reverse the cardiovascular abnormalities. CONCLUSIONS: Calcium, phosphate
      and magnesium functions are closely linked with abnormal plasma levels of these
      compounds often causing similar cardiovascular and neurological features.

PMID- 16573445
TI  - Worrying about normality.

PMID- 16573446
TI  - A 66 year old woman with a severe lactic acidosis and unusual anion gap following
      resuscitation from an asystolic cardiac arrest.

PMID- 16573447
TI  - Can a doctor enjoy a medical company's generosity without prescribing its
      products?

PMID- 16573448
TI  - Optimum mechanical ventilation for ARDS.

PMID- 16573449
TI  - Plan A, plan B and plan C: management of the difficult airway in the critically
      ill.

PMID- 16573450
TI  - Intravenous magnesium sulphate in acute coronary syndromes: are there any
      indications?

PMID- 16573451
TI  - Gastric emptying and nutrition in the critically ill patient.

PMID- 16573452
TI  - Does neostigmine increase gastric emptying in the critically ill?--results of a
      pilot study.
AB  - OBJECTIVE: Based on the successful use of neostigmine for the treatment of acute
      colonic pseudo-obstruction, we hypothesised that neostigmine would increase
      gastric emptying and improve tolerance to enteral feeding in the critically ill
      patient. METHODS: Eleven patients intolerant of enteral feeds due to high gastric
      aspirates, were randomised to receive a 'study infusion' consisting of either
      neostigmine (0.4 mg/hr) or 0.9% saline. If, after 12 hours the patient was deemed
      intolerant of the nasogastric feed, the rate of the 'study infusion' was doubled.
      Those who remained intolerant after 24 hours of the 'study infusion' were
      'crossed-over' and continued on the other infusion for a further 24 hours.
      Gastric emptying was assessed in each group before and after the infusion by
      measuring the hourly rates of feed "absorption" [(delivery rate + returned
      aspirates) - total aspirates] and paracetamol absorption using the area under a
      time-concentration curve at 120 minutes (AUC120). Differences within and between
      groups were analysed using Students t test and one-way analysis of variance.
      RESULTS: Six patients received neostigmine first and 5 received the placebo
      first. Four of the 6 patients receiving the neostigmine first compared with all
      of those receiving placebo first required to be 'crossed-over' to the other
      infusion. While the hourly rates of feed "absorption" were greater for patients
      receiving neostigmine than for placebo, these differences did not achieve
      statistical significance. The mean paracetamol AUC120 for all patients who
      received neostigmine was 3996 mg/min/L while that for placebo was 1929 mg/min/L
      (p = 0.21). CONCLUSIONS: These data suggest that while neostigmine may have a
      positive effect on gastric emptying and enteral feed absorption in critically ill
      patients, the results did not reach statistical significance and an adequately
      powered study will be required to confirm this effect.

PMID- 16573453
TI  - Candida parapsilosis fungaemia treated unsuccessfully with amphotericin B and
      fluconazole but eliminated with caspofungin: a case report.
AB  - A case of Candida parapsilosis Hickman catheter infection with fungaemia
      presenting with severe hypoxia, lactic acidosis and renal failure is described.
      Four months previously, the Hickman catheter had become infected with Candida
      parapsilosis (sensitive to fluconazole and amphotericin B) with blood cultures
      remaining positive despite an intravenous course of fluconazole 200 mg 12-hourly
      increasing to 400 mg-12-hourly. Subsequently, treatment with an amphotericin B
      infusion (30 mg over 24 hours) for five days was associated with a progressive
      increase in serum creatinine from 0.042 mmol/L to 0.278 mmol/L with blood
      cultures remaining positive. While arrangements were being made to remove and
      replace the catheter via a thoracotomy, the patient developed severe hypoxia,
      lactic acidosis and renal failure and was admitted to the intensive care unit for
      further management. An intravenous course of caspofungin (70 mg over 1 hour
      followed by 50 mg over 1 hour, daily) was associated with negative blood cultures
      and a normal plasma C-reactive protein for the first time in four months. The
      hypoxia was managed with spontaneous ventilation and high inspired oxygen
      concentrations, and the anaemia was treated with red blood cell transfusions. A
      rapid reversal of the respiratory failure and lactic acidosis occurred and the
      patient was discharged home from the intensive care unit after 10 days to
      continue the caspofungin infusions for a total of 6 weeks. She has subsequently
      remained well with negative blood cultures two months later.

PMID- 16573454
TI  - Hypertension in the critically ill patient.
AB  - OBJECTIVE: To review the management of persistent hypertension and hypertensive
      crisis in the critically ill patient. DATA SOURCES: A review of articles reported
      on hypertension and the critically ill patient. SUMMARY OF REVIEW: Hypertension
      is defined as a basal systolic blood pressure of greater than 140 mmHg or
      diastolic blood pressure of greater than 90 mmHg (MAP > 105 mmHg), irrespective
      of age and is based on the average of two or more readings on two or more
      occasions over a period of four weeks. While a mean arterial pressure in the
      critically ill up to a value of 135 mmHg may be tolerated for some hours, in
      patients with dissecting aortic aneurysm, cardiac failure, angina, acute
      myocardial infarction, pre-eclampsia and following cardiac, vascular or cerebral
      surgery a mean arterial blood pressure of > 90 mmHg or greater should be lowered
      by up to 30% urgently. A hypertensive crisis may be defined as a MAP > 160 mmHg
      and can be caused by phaeochromocytoma, sympathomimetic overdose, malignant
      hypertension or autonomic hyper-reactivity secondary to tetanus. Treatment
      requires direct intra-arterial monitoring and an initial reduction in mean
      arterial pressure by no greater than 30%. While management of the primary
      condition (e.g. surgical removal of a phaeochromocytoma, delivery or termination
      of the pregnancy) may also be necessary, infusions of sodium nitroprusside,
      phentolamine, hydralazine or esmolol usually require supplementation with oral
      agents (e.g. angiotensin-converting enzyme inhibitors, beta-adrenergic receptor
      antagonists and calcium-channel blockers) for long-term management. CONCLUSIONS:
      A mean arterial pressure in the critically ill is often tolerated up to a value
      of 135 mmHg for some hours. However in some disorders (e.g. dissecting aortic
      aneurysm, cardiac failure, angina, acute myocardial infarction, pre-eclampsia or
      eclampsia and following cardiac, vascular or cerebral surgery) a mean arterial
      blood pressure of 90 mmHg or greater should be treated urgently.

PMID- 16573455
TI  - Difficult airway management in the intensive care unit: practical guidelines.
AB  - OBJECTIVE: To review the management of the difficult airway in the intensive care
      unit patient. DATA SOURCES: A review of publications reported from 1975-2002 and
      identified in both the Medline and Pubmed databases on the management of the
      difficult airway. The publications were also assessed for their relevance to the
      intensive care setting. SUMMARY OF REVIEW: Endotracheal intubation is performed
      infrequently in the intensive care unit and usually in patients who have a higher
      than average rate of difficulty. The consequences of inadequate airway management
      can be devastating not only for the patient, but psychologically for the staff
      involved in whom airway management should be a core skill. Most of the reports
      reviewing the management of patients with a difficult airway are found in the
      field of anaesthesia and to a lesser extent in the field of emergency medicine.
      This review looks at the application of all the reported literature for difficult
      airway management in the intensive care setting. We propose guidelines that may
      assist both the trainee in intensive care medicine and the experienced
      intensivist in the management of the airway in the intensive care patient.
      CONCLUSIONS: The principles of difficult airway management, including a back-up
      plan and calling for assistance early, hold true in the intensive care setting as
      much as in any other clinical setting. It is vital that clinicians develop their
      own difficult airway algorithm based on their training and experience.

PMID- 16573456
TI  - Difficult airway management in the intensive care unit: alternative techniques.
AB  - OBJECTIVE: To review alternative airway management techniques and their
      suitability to the intensive care setting. DATA SOURCES: A review of publications
      reported from 1975-2002 and identified in both the Medline and Pubmed databases
      on the products used in the management of a difficult airway. In addition new
      airway devices were identified by accessing the product catalogues of major
      manufacturers and third-party vendors. The publications were assessed for their
      relevance to the intensive care setting. SUMMARY OF REVIEW: Many devices to
      manage the difficult airway have been designed for use in the controlled
      environment of an anaesthetic room rather than the intensive care unit. In
      addition, there is very little opportunity to evaluate and train with alternative
      techniques in real-life situations in the critical care setting. We review
      products that are considered as alternative airway devices to the standard
      endotracheal tube and include alternative intubating devices to the standard
      laryngoscope and devices to achieve a trans-tracheal airway. We also consider
      their suitability to the intensive care setting. CONCLUSIONS: There is a wide
      range of techniques available to manage the difficult airway. Due to the limited
      opportunity to train in the use of alternative airway techniques, such techniques
      should ideally involve an extension of those skills commonly practised by
      intensivists (e.g. bronchoscopy). Ultimately, the most important features when
      choosing a technique to manage a difficult airway are the training, knowledge and
      experience of the practitioner.

PMID- 16573457
TI  - High frequency oscillatory ventilation tidal volumes: how low can we go?

PMID- 16573458
TI  - A 37 year old man with intermittent abdominal pain and non-lactic, non-ketone,
      high anion gap metabolic acidosis.

PMID- 16573459
TI  - The power of magic.

PMID- 16573460
TI  - Clinical toxicology: 'bones' of contention.

PMID- 16573461
TI  - Predicting the need for renal replacement therapy and diuretic therapy in ICU:
      dopamine revisited?

PMID- 16573463
TI  - Ethyl alcohol: not always a benevolent agent.

PMID- 16573462
TI  - Insertion of neonatal intercostal catheters.

PMID- 16573464
TI  - Cervical spine clearance in unconscious ICU patients--room to improve.

PMID- 16573465
TI  - Cervical spine clearance in Australian intensive care units.
AB  - OBJECTIVE: Rigid or semi-rigid collar and spine board related complications may
      be causes of significant morbidity in intubated polytraumatised patients. As the
      process quantifying cervical spine injuries is controversial, exclusion of
      cervical spinal injuries (cervical spine clearance) can be delayed, thereby
      increasing complications associated with spinal cord immobilisation. We examined
      current practices in Australian ICUs by survey. METHODS: The intensive care unit
      or trauma services director and the senior nursing unit manager from 17 units
      within designated Australian trauma centres were surveyed separately by
      telephone. The presence of a written protocol for cervical spine clearance
      including radiological and clinical criteria, time goals for clearance,
      immobilisation methods and formal surveillance of collar related complications
      were assessed using a standardised questionnaire. RESULTS: All states and
      territories were represented. Of those services surveyed, only 50% had a written
      protocol, 50% had no specific time goal for cervical spinal clearance and the
      method of clearance ranged from plain cervical spine X-rays only to routine use
      of MRI. Immobilisation methods also varied, including use of rigid (hard) or soft
      collars with 71% having no formal surveillance of collar-related complications.
      Despite these results, 65% were satisfied with their approach to cervical spine
      clearance. CONCLUSIONS: There is no standardised approach to the clearance of the
      cervical spine in intubated trauma patients in Australian intensive care units.
      In addition, morbidity from current practices and the true incidence of cervical
      spine injuries remains unknown. We recommend use of a written protocol and formal
      documentation of collar related complications. A standardised approach to
      radiological and clinical clearance of cervical spine injuries, which is
      practical, yet safe, remains a subject for future risk-benefit analysis.

PMID- 16573466
TI  - Clinical predictors of acute renal replacement therapy in critically ill patients
      with acute renal impairment.
AB  - OBJECTIVE: To investigate the early predictors of acute renal replacement therapy
      (RRT) in critically ill patients with acute renal impairment. METHODS: A
      retrospective study of the clinical and laboratory records of all critically ill
      adult patients with acute renal impairment admitted to a 6-bed multidisciplinary
      intensive care unit of a general teaching hospital between 1 January 2000 and 31
      December 2001 were reviewed to determine risk factors for RRT. Acute renal
      impairment was defined as an acute increase in plasma creatinine of > 0.12 mmol/L
      and urea of > 8 mmol/L or an increase in plasma creatinine of > 0.06 mmol/L from
      the baseline level in patients who had chronic renal impairment. RESULTS: A
      cohort of 179 critically ill patients with acute renal impairment were
      identified. The mean APACHE II score was 23.4 and RRT was required in 11.2% of
      patients. The final logistic regression model showed that the requirement for
      noradrenaline (OR 29.0; 95% CI: 1.92 - 436.4, p = 0.015) was a positive risk
      factor and an increase in the average hourly urine output after intravenous
      frusemide (post-frusemide average hourly urine output/pre-frusemide average
      hourly urine output, OR 0.08; 95% CI: 0.02 - 0.32, p = 0.0004) was a negative
      risk factor for the requirement of RRT (area under the ROC curve = 0.88, 95% CI:
      0.82 - 0.94, p = 0.001). CONCLUSIONS: After adequate fluid resuscitation, poor
      urinary output response to intravenous frusemide coupled with requirement for
      noradrenaline predicted the requirement for RRT in critically ill patients with
      early acute renal impairment in our intensive care unit.

PMID- 16573467
TI  - Insertion distance of neonatal intercostal catheters using a 10 French Argyle
      trocar thoracic catheter.
AB  - OBJECTIVE: We believed that intercostal catheters were often inserted too far
      into the thoracic cavity in neonatal patients. The aim of this study was to
      determine the average distance from the catheter tip to the midline, of
      intercostal catheters inserted in our neonatal unit and the incidence of
      catheters that were inserted too far into the thoracic cavity. METHODS: During a
      two year period we examined the chest X-rays of all infants who had an
      intercostal catheter inserted using an Argyle 10 French trocar thoracic catheter
      for drainage of a pneumothorax. For each initial chest X-ray following the
      insertion of the intercostal catheter we measured the horizontal distance in mm
      from catheter tip to the midline. The tip to midline distance was zero if the tip
      was at the midline and negative if it crossed the midline. To standardise the tip
      to midline distance for different size infants we measured the distance in 'inter
      vertebral' units. RESULTS: During the two year period, 13 of 24 intercostal
      catheters (54%) crossed the midline (i.e. were inserted too far). The mean (+/-
      SD) tip to midline distance was -1.29 (+/- 13.9) mm with a range varying between 
      40 to 34 mm with a calculated 'inter-vertebral' units mean (+/- SD) tip to
      midline distance of -0.32 (+/- 1.9) range -4.6 to 4.0. CONCLUSIONS: Fifty four
      percent of the intercostal catheters inserted in our unit were inserted too far.
      As the distance markings on the Argyle intercostal catheters are marked from the
      last side-hole rather than from the tip of the catheter, Argyle intercostal
      catheters may be inadvertently inserted two centimetres further than they should
      be.

PMID- 16573468
TI  - Severe ethanol poisoning: a case report and brief review.
AB  - A case of severe ethanol toxicity is described where a patient was admitted
      pulseless, apnoeic and deeply unconscious after ingesting a full bottle (1 litre)
      of 'methylated spirits' The initial blood ethanol level was 1.127 g/dL. The
      patient was rapidly intubated and resuscitated with fluids and inotropic agents.
      Renal replacement therapy was initiated and a rapid reduction in the initial
      blood ethanol level occurred. Twenty-one hours after her admission she was
      conscious and cooperative and was discharged from the intensive care unit without
      any clinical evidence of brain injury. Ethanol toxicity is common although
      ethanol poisoning leading to death is rare. Nevertheless, severe toxicity can
      cause medullary paralysis with respiratory failure and death. Rapid resuscitation
      and, in severe cases, renal replacement therapy may be warranted as the outlook
      for patients who recover is excellent.

PMID- 16573469
TI  - Nutrition in the critically ill patient: part I. Essential physiology and
      pathophysiology.
AB  - OBJECTIVE: To review the human nutrition in the critically ill patient in a three
      part presentation. DATA SOURCES: Articles and published peer-review abstracts and
      a review of studies reported and identified through a MEDLINE search of the
      English language literature on parenteral nutrition. SUMMARY OF REVIEW: In a
      healthy individual, nutrition involves an alternating system of feeding and
      fasting, with periods of fasting longer than 72 hr inducing a state of
      starvation. The hormonal response to nutrition is substrate controlled with
      glucose and amino acids, during the fed state, stimulating insulin secretion and
      decreasing glucagon secretion. Glycogen reserves and protein synthesis increase
      and the excess carbohydrate, amino acids and fats are stored as lipid. During the
      fasted state, plasma levels of glucose and amino acids fall, reducing insulin
      secretion and increasing glucagon secretion, stimulating gluconeogenesis and
      glycogenolysis. A further reduction in insulin and increase in glucagon secretion
      occurs during starvation and mild sympathetic activation stimulates
      hormone.sensitive lipoprotein lipase to increase the release of free fatty acids
      (FFAs) from adipose tissue. Much of the excess FFAs are converted by the liver to
      ketone bodies. During injury and sepsis the nutritional hormones are no longer
      substrate controlled. For example, during injury, to maintain haemodynamic
      homeostasis, an increase in sympathetic tone and catecholamine (i.e. adrenaline
      and noradrenaline) secretion occurs, and in the septic state, in addition to the
      hormonal stress response, polypeptide mediators of tumour necrosis factor (TNF
      alpha) and interleukin-1 are liberated, causing an increase in glucose
      intolerance and an increase in skeletal muscle protein catabolism. Optimal
      nutritional support in the critically ill patient can only be achieved when the
      patient is in the convalescent phase of injury, as nutritional supplementation
      will not reverse the factors causing proteolysis, gluconeogenesis or lipolysis
      associated with stress or sepsis. Therapy should therefore focus upon decreasing
      or reducing the factors causing the acute illness before nutritional
      supplementation can be given with benefit. CONCLUSIONS: In the critically ill
      patient nutritional hormones are no longer substrate controlled with glucose,
      amino acid and lipid intolerance often occurring when given to excess. While
      nutritional supplementation is often required, particularly during a prolonged
      illness, the influence of stress and sepsis should be minimised while the
      nutritional substrates are being provided.

PMID- 16573470
TI  - Nutrition in the critically ill patient: part II. Parenteral nutrition.
AB  - OBJECTIVE: To review the human nutrition in the critically ill patient in a three
      part presentation. DATA SOURCES: Articles and published peer-review abstracts and
      a review of studies reported and identified through a MEDLINE search of the
      English language literature on parenteral nutrition. SUMMARY OF REVIEW:
      Intravenous nutrition plays an important supportive role in the management of the
      critically ill patient who has prolonged gastrointestinal failure. Energy
      substrates consist of concentrated glucose and lipid solutions, although the
      former requires central venous access for its administration. The nitrogen
      requirement is supplied as L-amino acids which usually consist of a solution
      containing the essential amino acids which are supplemented by a few of the non
      essential amino acids. While, amino acid mixtures of glutamine dipeptides,
      ornithine alpha-ketoglutarate, asparagine, oxaloacetate, arginine, aspartate and
      glutamate have been used in a variety of conditions, prospective randomised
      controlled trials have not consistently demonstrated improved survival with their
      use in the critically ill patient. The water soluble vitamins and vitamin K
      should supplement intravenous nutrition with amounts at least to meet the
      recommended daily allowance. Additional supplementation of thiamine, folic acid
      and ascorbic acid are often administered in the critically ill patient. Apart
      from zinc, the body stores of the essential trace elements of zinc, copper,
      iodine, iron, manganese, cobalt, selenium, chromium, fluoride and molybdenum are
      usually adequate to meet the needs of patients requiring parenteral nutrition for
      less than 3 months. CONCLUSIONS: In the critically ill patient with prolonged
      gastrointestinal failure, intravenous nutrition plays a supportive role in the
      management of a patient.

PMID- 16573471
TI  - Some aspects of the design and monitoring of clinical trials.

PMID- 16573472
TI  - A 19 year old woman admitted to hospital confused and agitated with intermittent
      twitching of her upper and lower limbs.

PMID- 16573473
TI  - Are intensive care units self-sustaining?

PMID- 16573474
TI  - Does the patient need more fluid?

PMID- 16573475
TI  - The toxic shock syndrome: inhibiting superantigens or treating their adverse
      effects?

PMID- 16573476
TI  - Oversedation and agitation in the intensive care unit: vacillate or automate.

PMID- 16573477
TI  - Antibiotic prophylaxis. How, when and why.

PMID- 16573478
TI  - Preload response in patients after cardiac surgery: a comparison of systolic
      blood pressure and systolic area variability and initial volume of distribution
      of glucose.
AB  - OBJECTIVE: Estimation of stroke volume variation (e.g. systolic blood pressure
      and systolic area variability) and central extracellular compartment volume (e.g.
      initial volume of distribution of glucose, IVDG) may be useful in guiding fluid
      therapy in mechanically ventilated patients. The reliability of systolic blood
      pressure (SBP) variability has been well validated, but little is known about
      systolic area (SA) variability or IVDG. Our aim was to investigate SBP and SA
      variability and IVDG as predictors of preload responsive hypovolaemia in post
      cardiac surgery patients. METHODS: Thirty-four mechanically ventilated patients
      undergoing preload enhancement post elective cardiac surgery were studied. The
      maximum-minimum difference and power spectral measurement of SBP and SA
      variability were derived from the arterial waveform trace and examined before and
      after rapid volume infusion. IVDG was determined prior to volume infusion from
      three-minute incremental glucose estimation and (with SBP and SA variability)
      correlated with subjects classified as hypotensive and preload responsive.
      RESULTS: Neither IVDG or SA and SBP variability were found to correlate with
      subjects identified as hypotensive and preload responsive. However, the power
      spectral measures of SBP and SA variability were significantly reduced (p = 0.007
      and p = 0.026, respectively) following preload enhancement in fluid responsive
      subjects. CONCLUSIONS: Our results indicate that neither IVDG, nor SBP and SA
      variability are predictive of preload responsive hypotension in post-cardiac
      surgery patients. Spectral analysis of SBP and SA may be more sensitive at
      assessing preload responsiveness in this patient group than traditional maximum
      minimum measures.

PMID- 16573479
TI  - Interpreting CSF lactic acidosis: effect of erythrocytes and air exposure.
AB  - OBJECTIVE: Elevated cerebrospinal fluid (CSF) lactate concentrations in
      neurotrauma and sub-arachnoid haemorrhage are associated with a poor prognosis.
      However, in blood-stained CSF, elevated lactate levels may arise from red cell
      metabolism, even without ischaemia, potentially reducing specificity. This study
      was undertaken to quantify the erythrocyte contribution to CSF lactate
      measurements, with and without, exposure to room air. METHODS: Blood was added to
      CSF to achieve three different red cell concentrations. The CSF was then exposed
      at 37 degrees C to either room air or 5% CO2 and 95% oxygen. Vancomycin and
      gentamycin were added to inhibit bacterial growth. Lactate concentrations and red
      cell concentrations were measured prior to the addition of blood and 10 minutes,
      6 hours and 24 hours later. CSF without the addition of blood was used as a
      control. RESULTS: In the control specimens there were no increases in CSF lactate
      concentrations over time, either in air or CO2, whereas all specimens with blood
      added demonstrated significant increases in lactate at 6 and 24 hours (P < 0.01).
      The lactate increases in both air and CO2 were correlated directly with red cell
      counts (R2 = 0.62 to 0.87). At all red cell concentrations, the mean lactate
      increase was greater in air. CONCLUSIONS: Red cells in CSF cause significant
      increases in lactate concentrations, more so when exposed to air. This should be
      considered when interpreting lactate in blood stained CSF. Blood-stained CSF
      specimens for lactate assay should be collected directly from an external
      ventricular drain rather than a reservoir bag.

PMID- 16573480
TI  - Antibiotic prophylaxis for external ventricular drains in neurosurgical patients:
      an audit of compliance with a clinical management protocol.
AB  - OBJECTIVE: To examine the clinical impact of a management protocol for external
      ventricular drains (EVD). PATIENTS AND METHODS: All patients with EVDs over a six
      month period were reviewed retrospectively. Data concerning the indications for
      EVD placement, antibiotics and cerebrospinal fluid (CSF) analyses were collected.
      A restrictive antibiotic protocol (e.g. intravenous cephalothin 1g 6-hourly for
      24 hours, unless other antibiotics were prescribed for a documented pre-existing
      infection) was introduced for all patients requiring placement of an EVD during
      the following six months and all patients were observed prospectively. Daily CSF
      samples were collected under sterile conditions and examined for organisms,
      cells, glucose and protein and sent for microbiological culture. External
      ventricular drains were removed after five days and replaced if further
      monitoring or CSF drainage was required. Adherence to the protocol and the
      incidence of ventriculitis was determined. RESULTS: Twelve patients with EVDs
      were identified during the 6 month pre-protocol period and 15 patients with EVDs
      were identified during the 6 month post-protocol period. There was no significant
      difference between the total (72 vs 88 days) and mean (6 vs 5.9 days) drain
      placement times between the two groups. There was no significant difference
      between the mean numbers of CSF samples in the two groups. CSF aspirates were not
      analysed in 35/72 samples (49%) in the pre-protocol group compared with 45/88
      (51%) samples in the post-protocol group. Positive CSF Gram-stains were found in
      3/12 (25%) patients in the pre-protocol group and in 0/15(0%) in the post
      protocol group. Positive CSF cultures decreased significantly in the post
      protocol group (17 vs 5, p = 0.0009). Prophylactic antibiotics were prescribed in
      5/12 (42%) patients in the pre-protocol group compared with 12/15 (80%) patients
      in the post-protocol group. CONCLUSIONS: The protocol was associated with a
      statistically significant improvement in compliance with antibiotic prescription
      and reduction in the incidence of positive CSF cultures.

PMID- 16573481
TI  - Iodine induced thyrotoxicosis following povidine-iodine dressings: a case report.
AB  - A 40-year-old woman was admitted to the intensive care unit after a radical
      resection of a recurrent abdominal malignancy. Her postoperative course was
      complicated by sepsis requiring numerous abdominal operations with the abdomen
      being left open for drainage and dressings. Use of povidone-iodine soaked
      abdominal packs to reduce secondary infection led to development of
      thyrotoxicosis, which resolved following the cessation of the iodine dressings. A
      high index of suspicion is needed for the diagnosis of this condition in
      intensive care patients as the usual haemodynamic signs of thyrotoxicosis may be
      misinterpreted as being caused by sepsis.

PMID- 16573482
TI  - Activated protein C in toxic shock syndrome: a case report.
AB  - The mortality from septic shock remains high despite the availability of modern
      critical care facilities. In recent years, new agents have been tested to reduce
      morbidity and mortality in patients with severe sepsis. Among them, recombinant
      human activated protein C (rhAPC) has been reported to significantly reduce
      mortality and morbidity in patients with severe sepsis and one or more acute
      organ failures. We describe our experience with this drug in the early reversal
      of septic shock from toxic shock syndrome.

PMID- 16573483
TI  - The Atkins Diet as a possible trigger for an ICU admission: a case report.
AB  - A case of initial presentation and diagnosis of hereditary coproporphyria is
      described, following a patient's first seizure in the surgical ward, where she
      had been admitted for investigation of abdominal pains. The frequency of
      seizures, motor neuropathy and florid visual hallucinations worsened over the
      subsequent days, until the definitive investigations revealed the diagnosis and
      specific therapies were instituted. The acute porphyrias, a rare group of
      conditions caused by deficiencies in enzymes involved in haem biosynthesis, are
      associated with significant morbidity and occasional mortality. Consideration of
      the diagnosis, combined with appropriate supportive and specific therapies can
      reduce the duration of the crisis and lessen the rates of morbidity and mortality
      associated with these conditions.

PMID- 16573484
TI  - Rethinking sedation and agitation management in critical illness.
AB  - OBJECTIVE: To examine difficulties in sedation management in the critically ill
      patient and explore how a semi automated sedation controller can improve
      agitation control. To present recent work on measurements of agitation, dynamic
      systems modelling and control of patient agitation response. DATA SOURCES:
      Articles and peer-reviewed studies identified through a PUBMED search and
      selected original works from the biomedical engineering literature of relevance
      to agitation control and management. SUMMARY OF REVIEW: Over-sedation has an
      adverse impact on intensive care resources. Interventions to constrain sedation
      delivery through development of protocols or regular cessation of infusions
      result in reduction in resource utilisation, but have not significantly addressed
      existing difficulties in agitation control. We develop a paradigm in which
      control of agitation in critically ill patients becomes the primary objective of
      sedation management. This principle is central to the function of a nurse-managed
      semi-automated sedation delivery device. The clinical application of this device
      using subjective assessments of agitation is presented. A framework for the
      development of improved automated sedation delivery systems using objective
      measurements of agitation and control, based on agitation feedback, is described.
      Using dynamic systems modelling and a simulated nurse, a bolus-driven approach
      significantly reduced agitation and minimised drug utilisation. This result
      challenges the current practice of sedating patients using continuous infusions.
      CONCLUSIONS: A simple computerised interface with an algorithm that continually
      reduces the infusion rate in the absence of agitation has successfully been
      introduced into clinical practice. Nursing staff reported high levels of
      satisfaction with this device and it has enabled detailed data on patterns of
      sedation administration to be extracted for analysis. This data has been used to
      validate a model of the fundamental agitation-sedation dynamics.

PMID- 16573485
TI  - Nutrition in the critically ill patient: part III. Enteral nutrition.
AB  - OBJECTIVE: To review the human nutrition in the critically ill patient in a three
      part presentation. DATA SOURCES: Articles and published peer-review abstracts and
      a review of studies reported and identified through a MEDLINE search of the
      English language literature on enteral nutrition. SUMMARY OF REVIEW: Enteral
      nutrition is indicated in the critically ill patient when there is an inability
      to ingest adequate nutrients by mouth and where the gastrointestinal tract is
      otherwise normal. The commonly used polymeric feeding solutions provide a mixture
      of nutrients similar to that encountered in the normal diet, usually as an iso
      osmolar low residue solution. Because lactose intolerance may be encountered
      during critical illness, most formulations are lactose free. Special glutamine
      formulations and immune enhancing enteral formula (e.g. enriched with 3 fatty
      acids, arginine and ribonucleic acids) have been used in critically ill patients.
      However there have been few studies to indicate that these diets are of greater
      benefit compared with normal enteral formulations. The daily nutritional
      requirements are often not met in critically ill patients largely due to delayed
      gastric emptying or diarrhoea. Prokinetic agents, special formulations containing
      fibre and probiotics, have been used in an attempt to improve the tolerance to
      the formulations, although there have been no comparative studies that allow firm
      recommendation to be made. In general, a standard enteral solution is usually
      prescribed first and instilled into the stomach using a fine bore nasogastric
      tube. If gastric emptying is delayed prokinetic agents are tried before a
      transpyloric tube or enterostomy tube feeding is considered. CONCLUSIONS:
      Nutritional requirements for the critically ill patient should be delivered
      enterally in patients who have a normally functioning gastrointestinal system. A
      standard formulation is usually prescribed and instilled into the stomach using a
      fine bore tube. If gastric emptying is delayed prokinetic agents are tried before
      a transpyloric tube or enterostomy tube feeding is considered. Diarrhoea caused
      by enteral pathogens may require specific treatment. If pathogens are excluded
      then fibre and probiotics may be considered. Motility reducing agents (e.g.
      opiates) may cause abdominal bloating.

PMID- 16573486
TI  - The interpretation of lack of evidence of a difference in efficacy: equivalence
      trials and the treatment of fungal infections.

PMID- 16573487
TI  - A 70 year old man with aphasia and agitation.

PMID- 16573488
TI  - In the beginning. The 1952-1953 Danish epidemic of poliomyelitis and Bjorn Ibsen.

PMID- 16573490
TI  - A word from the congress president.

PMID- 16573489
TI  - Monitoring intestinal ischaemia. More problems!

PMID- 16573491
TI  - Written guidelines for laboratory testing.

PMID- 16573492
TI  - Clinical features of an increase in intracranial pressure.

PMID- 16573493
TI  - Reporting of clinical trials using group sequential methods.

PMID- 16573494
TI  - Effect of ventilation equipment on imposed work of breathing.
AB  - OBJECTIVE: To determine the imposed work of different ventilation systems at 3
      levels of pressure support. DESIGN: Laboratory study. SETTING: Teaching hospital
      respiratory laboratory. PARTICIPANTS: Healthy, human volunteers. INTERVENTIONS:
      Measurement of imposed work of breathing (WOB(i)) in six ventilators with
      alteration of ventilatory settings, humidification device, and triggering
      mechanisms. RESULTS: At 0 cmH2O CPAP and 0 cmH2O PSV, clinically significant (>
      0.1 joules per litre or J/L) WOB(i )occurred in all systems. At 5 cmH2O pressure
      support ventilation (PSV) median WOB(i) ranged from 0.01 to 0.11 J/L. Removal of
      the pleated membrane heat and moisture exchanger (HME) significantly reduced
      WOB(i) (0.38 vs. 0.11 J/L, p < 0. 0001). Drawover humidification marginally
      increased WOB(i) (0.16 vs. 0.11 J/L, p = 0. 0001). Flow triggering reduced WOB(i)
      with the Servo (p < 0.0001) and Bennett ventilators (p = 0.001) but not with the
      Bear 1000 ventilator. CONCLUSIONS: Up to 7 cmH2O of PSV may be required to reduce
      WOB(i) related to the ventilator, circuit and humdification devices. This
      pressure support does not address the additional resistive effect of the
      endotracheal or tracheotomy tube. Higher levels of PSV may therefore be required
      to offset WOB(i).

PMID- 16573495
TI  - Factors contributing to fatal outcome of traumatic brain injury: a pilot case
      control study.
AB  - OBJECTIVE: Patients with traumatic brain injury (TBI) have a high mortality and
      morbidity. This pilot study was undertaken to identify contributors to outcome in
      the early management of patients with TBI and to investigate the feasibility of a
      larger study. METHODS: Road trauma patients who died between January 1 and April
      30, 2000 were selected from the Alfred Hospital's Intensive Care Traumatic Brain
      Injury database. These patients were matched with 2 survivors from the data base
      during the same period for age, injury severity score (ISS) and severity of brain
      injury using the head abbreviated injury score (head AIS). Patient injury scoring
      (using the revised trauma score, trauma and injury severity score and Glasgow
      coma score), arterial blood gas analysis, lactate concentration, inspired oxygen
      concentration, systolic and mean arterial blood pressure, intracranial pressure,
      intravenous fluid and blood transfusion volumes, body temperature, haemoglobin,
      white cell count, INR, APTT, temperature and plasma glucose, urea and creatinine
      concentrations were recorded for 48 hours from the time of injury. Time periods
      from the accident to key events (e.g. arrival of ambulance at accident scene,
      intubation, arrival at the emergency department, insertion of intracranial
      pressure monitor and primary surgery) were also recorded. RESULTS: Eighteen
      patients (6 deceased, 12 survivors) were identified. Despite matching, deceased
      patients had lower initial Glasgow Coma Scores (GCS) (3.6 vs. 7.4, P = 0.01) and
      lower revised trauma scores (4.41 vs. 5.75; P = 0.044) compared with survivors.
      There were no significant differences in other parameters. However, deceased
      patients tended to have longer times to treatment (P = NS) and experienced trauma
      at night more frequently, and survivors received almost double the volume of
      fluid resuscitation during the first 12 hours (19.7 +/- 19.1 vs. 11.8 +/- 2.7
      mL/kg/hr, P = 0.513). CONCLUSIONS: Both initial GCS and severity of brain injury
      should be used to match TBI patients for injury severity in future studies. Lower
      initial GCS in deceased patients was likely due to greater severity of brain
      injury, although it is also possible that the lower GCS was due to decreased
      brain perfusion (perhaps reflecting inadequate resuscitation) in these patients.
      Volume of early fluid resuscitation, time to definitive therapy, and time of
      presentation to hospital may also be important determinants of patient outcome. A
      large case control outcome study is required to extend these observations.

PMID- 16573496
TI  - Written guidelines for laboratory testing in intensive care--still effective
      after 3 years.
AB  - OBJECTIVE: The aim of the study was to examine the effect of time on written
      guidelines for laboratory testing in an intensive care unit by comparing the
      numbers of tests performed with those performed three years previously. METHODS:
      In 1995, guidelines were developed for blood test ordering in the Waikato
      Hospital intensive care unit, which when implemented resulted in a decrease in
      all blood tests performed by 16.6% in a group of general intensive care patients
      and by 25.9% in a group of post cardiac surgery patients. We repeated this study
      on similar groups of patients to see if the guidelines were still effective. Data
      on age, APACHE II score, diagnosis, and ventilation time were collected.
      Comparisons were made of tests performed per patient and per ventilation time in
      hours. RESULTS: In the general intensive care patient group, there was an
      increase of 2.1% tests performed per patient, but a decrease in tests performed
      per ventilation time of 5.6%. In the postoperative cardiac surgery patient group,
      the total number of tests performed per ventilation time decreased by 4%. The
      arterial blood gases performed per patient increased by 10.7% in the general
      intensive care patient group, and decreased by 14.3% in the postoperative cardiac
      surgery patient group. However, when the number of arterial blood gases performed
      per ventilation time were compared with the 1995 study, there was no difference
      in the general intensive care patient group, while there was a reduction by 8.3%
      in the postoperative cardiac surgery patient group. CONCLUSIONS: Three years
      after the implementation of guidelines for laboratory testing in an intensive
      care unit, there was no return to the level of testing recorded before the
      guidelines were introduced. The number of tests per ventilation time decreased by
      4% in postoperative cardiac surgery patients and decreased by 5.6% in the general
      intensive care patients. In our study written guidelines remained effective three
      years after their introduction.

PMID- 16573497
TI  - Tetanus managed in a peripheral hospital--a case report and a review of
      management.
AB  - Tetanus has become increasingly uncommon. However, with many people failing to
      maintain adequate levels of immunisation it will continue to present
      sporadically, with patients who are affected frequently requiring intensive care
      management. A case of tetanus, and its management in a peripheral hospital in New
      Zealand, is described. Current treatment options are reviewed.

PMID- 16573498
TI  - Transient epidermal flushing in a head injured patient: a case report.
AB  - An unusual case of transient epidermal flushing after median nerve stimulation
      and endotracheal suctioning in a patient with head injury is described. The
      mechanisms of transient erythematous skin reactions in a head injured patient are
      discussed.

PMID- 16573499
TI  - An intermittent foreign body in the airway: a case report.
AB  - A case is described of a surgical 'stay' suture which apparently disappeared from
      the tracheostomy site and took an unusual course before it reappeared in the
      patient's tracheostomy tube. Our report highlights the importance of
      documentation of the surgical techniques and procedures used in the performance
      of a tracheostomy and the importance of daily bedside examinations in the
      critically ill patient.

PMID- 16573500
TI  - Monitoring intestinal ischaemia.
AB  - OBJECTIVE: To review the clinical and experimental methods of detecting
      intestinal ischaemia and to assess their value in current clinical practice. DATA
      SOURCES: Relevant articles and published reviews on intestinal ischaemia and/or
      infarction. SUMMARY OF REVIEW: The incidence of acute mesenteric ischaemia has
      increased substantially over the last few decades. Death rates of 70% to 90% have
      been reported for this condition. Improved management depends upon prompt
      diagnosis and early aggressive management. Despite mounting evidence that
      ischaemic intestinal injury may be frequent and may be a cause of multi-organ
      failure, accurate monitor-ing of the intestinal circulation in critically ill
      patients continues to be a distant goal. The need for a reliable, specific test
      of intestinal ischaemia has been recognised for many years. Numerous potential
      monitors have been evaluated including intraluminal pCO2, abdominal CT, abdominal
      MRI and specific plasma enzymes, but few have shown potential to be clinically
      useful. At present no specific test for intestinal ischaemia and/or infarction is
      in routine clinical use. Development of a specific test to monitor for intestinal
      injury would be of great clinical value. Further work will inevitably lead to the
      development of useful markers. CONCLUSIONS: Accurate detection of intestinal
      ischaemia in the critically ill patient is often difficult. While numerous tests
      have been examined to diagnose and monitor intestinal ischaemia and/or infarction
      most exhibit an unacceptably low specificity and sensitivity.

PMID- 16573501
TI  - Acid-base balance: part I. Physiology.
AB  - OBJECTIVE: To review the normal human acid-base physiology and the
      pathophysiology and management of acid-base disturbances in a two-part
      presentation. DATA SOURCES: Articles and published peer-review abstracts and a
      review of studies reported from 1990 to 2000 and identified through a MEDLINE
      search of the English language literature on acid-base balance. SUMMARY OF
      REVIEW: In a healthy individual the extracellular fluid pH change following
      addition of a metabolic acid or base, is modified initially by the body's
      buffers. Subsequent respiratory compensation, by excretion or retention of CO2,
      modifies this change before metabolism of the organic acid or renal excretion of
      the acid or alkali returns the plasma bicarbonate to normal. A primary
      respiratory acid base change is modified initially by cellular buffers, with
      renal compensatory mechanisms adjusting slowly to this change. However,
      correction of the respiratory pH disorder only occurs with correction of the
      primary disease process. CONCLUSIONS: In man the acid-base balance is maintained
      and regulated by the renal and respiratory systems, which modify the
      extracellular fluid pH by changing the bicarbonate pair (HCO3- and PCO2); all
      other body buffer systems adjust to the alterations in this pair.

PMID- 16573502
TI  - Acid-base balance: part II. Pathophysiology.
AB  - OBJECTIVE: To review the normal human acid-base physiology and the
      pathophysiology and management of acid-base disturbances in a two-part
      presentation. DATA SOURCES: Articles and published peer-review abstracts and a
      review of studies reported from 1990 to 2000 and identified through a MEDLINE
      search of the English language literature on acid-base balance. SUMMARY OF
      REVIEW: Acid-base disorders are usually classified as metabolic (non-respiratory)
      or respiratory, depending on whether the primary change occurs in the plasma
      bicarbonate or the carbonic acid (i.e. carbon dioxide) concentrations,
      respectively. Respiratory or renal compensatory changes usually occur to minimise
      the effect of the primary disturbance. A metabolic acidosis arises from an
      abnormal process that generates non-carbonic acid or an abnormal loss of HCO3-
      and may be identified by an increase or normal anion gap, respectively. The
      arterial blood gas usually reveals a pH < 7.36, PCO2 < 35 mmHg and 'calculated'
      HCO3- < 18 mmol/L. In general, a high anion gap acidosis is managed by treating
      the disorder generating the acid (thereby ceasing the acid production) and
      enhancing the clearance of the acid anion (e.g. by metabolism or excretion)
      thereby regenerating the HCO3- reduced by buffering. A metabolic alkalosis arises
      from an abnormal process generating excess HCO3-. The arterial blood gas usually
      reveals a pH > 7.44, PCO2 > 45 mmHg and 'calculated' HCO3- > 32 mmol/L. As the
      kidney has a large capacity to excrete HCO3-, management usually requires
      treatment of the processes that are generating as well maintaining the alkalosis.
      Respiratory acidosis and alkalosis are usually caused by a primary disorder of
      carbon-dioxide excretion, and correction of the pH disorder only occurs with
      correction of the primary disease process. CONCLUSIONS: In man, acid-base
      disturbances are usually classified as either metabolic or respiratory.
      Correction of the underlying disorder is often all that is required to allow the
      body to metabolise or excrete the acid or alkali and return the buffer pair (HCO3
      and PCO2) to normal.

PMID- 16573503
TI  - A 65 year old man admitted to intensive care with hyperkalaemia and LBBB
      following coronary artery bypass surgery.

PMID- 16573504
TI  - Blood purification in sepsis: reasonable scientific hypothesis or pipe dream?

PMID- 16573505
TI  - Please read the fine print.

PMID- 16573507
TI  - Treatment options for refractory intracranial hypertension: the evidence-based
      cupboard is bare.

PMID- 16573506
TI  - The teleology of inflammation--doing battle with the selfish gene.

PMID- 16573508
TI  - Rare and emerging infections.

PMID- 16573510
TI  - Further reflections on clinical trials in critical care.

PMID- 16573509
TI  - Is endotracheal suctioning an art or science?

PMID- 16573511
TI  - The effect of closed system suction on airway pressures when using the Servo 300
      ventilator.
AB  - OBJECTIVES: To measure airway pressures during closed system suctioning with the
      ventilator set to three differing modes of ventilation. METHODS: Closed system
      suctioning was conducted in 16 patients following cardiac surgery. Suctioning was
      performed using a 14 French catheter with a vacuum level of -500 cmH2O through an
      8.0 mm internal diameter endotracheal tube. The lungs were mechanically
      ventilated with a Servo 300 ventilator set to one of three ventilation modes:
      volume-control, pressure-control or CPAP/pressure support. Airway pressures were
      measured via a 4 French electronic pressure transducer in both proximal and
      distal airways. RESULTS: Following insertion of the suction catheter, end
      expiratory pressure increased significantly (p < 0.001) in both pressure-control
      and volume-control ventilation. This increase was greatest (p = 0.018) in volume
      control mode (2.7 +/- 1.7 cmH2O). On performing a five second suction, airway
      pressure decreased in all modes, however the lowest airway pressure in volume
      control mode (-4.9 +/- 4.0 cmH2O) was significantly (p = 0.001) less than the
      lowest airway pressure recorded in either pressure-control (0.8 +/- 1.9 cmH2O) or
      CPAP/pressure support (0.4 +/- 2.8 cmH2O) modes. In CPAP/pressure support mode,
      13 of the 16 patients experienced a positive pressure 'breath' at the end of
      suctioning with airway pressures rising to 21 +/- 1.6 cmH2O. CONCLUSIONS: Closed
      system suctioning in volume control ventilation may result in elevations of end
      expiratory pressure following catheter insertion and subatmospheric airway
      pressures during suctioning. Pressure control ventilation produces less elevation
      of end-expiratory pressure following catheter insertion and is less likely to be
      associated with subatmospheric airway pressures during suctioning. CPAP/pressure
      support has no effect on end-expiratory pressure following catheter insertion and
      subatmospheric airway pressures are largely avoided during suctioning.

PMID- 16573512
TI  - Procalcitonin in critical illness.
AB  - OBJECTIVE: To detail the biology and diagnostic usefulness of serum procalcitonin
      in critical illness. DATA SOURCES: A review of articles published in peer
      reviewed journals from 1990 to 2001 and identified through a MEDLINE search on
      procalcitonin. SUMMARY OF REVIEW: Procalcitonin (PCT) is a prohormone of
      calcitonin. Serum levels are elevated during sepsis and have been identified as a
      potential marker of infection in critical illness. However, its function and
      precise source of origin during sepsis remain unclear. The value of estimating
      serum PCT appears to be in the differentiation of infectious from non-infectious
      forms of systemic inflammatory response syndrome. A number of studies also point
      to its usefulness in distinguishing between bacterial and viral meningitis.
      However, there are a number of non-infectious conditions, where elevations in
      serum PCT occur, reducing its specificity. Its superiority as a marker of sepsis
      compared with other acute phase reactants continues to be debated. CONCLUSIONS:
      The utility of serum procalcitonin as a diagnostic test of sepsis is still under
      evaluation. Moreover, a number of unanswered questions remain regarding the
      biological role of PCT during sepsis, its target receptors and its protective
      value to the patient.

PMID- 16573513
TI  - Circulating secretory phospholipase A2 in critical illness--the importance of the
      intestine.
AB  - OBJECTIVE: To review the role of secretory phospholipase A2 in the pathogenesis
      of multiple organ failure in the critically ill patient. DATA SOURCES: Relevant
      articles and published reviews on secretory phospholipase A2 in critical illness.
      SUMMARY OF REVIEW: Secretory phospholipase A2 (sPLA2) has an important role in
      inflammation and in antimicrobial defence. However, excessive activity of sPLA2
      has been shown to result in tissue damage and has been implicated as a mediator
      of organ failure associated with critical illness. Gastrointestinal release of
      secretory phospholipase A2 from Paneth cells increases during intestinal
      ischaemia and may be an important factor in the pathogenesis of the multiple
      organ dysfunction syndrome. In experimental models, specific PLA2 inhibitors
      reduce organ failure associated with sPLA infusion and may play an important role
      in reducing organ failure in the management of the critically ill patient.
      CONCLUSIONS: Intestinal ischaemia may play an important role in the pathogenesis
      of the multiple organ dysfunction syndrome in the critically ill patient. In
      patients with sepsis, specific PLA2 inhibitors have the potential to reduce organ
      failure and improve morbidity and mortality.

PMID- 16573514
TI  - Thoracic CT for the intensivist.
AB  - OBJECTIVE: To discuss the recent advances in computed tomography (CT) and to
      present a simplified approach to CT of the chest to facilitate the understanding
      and diagnosis of common acute thoracic abnormalities in the critically ill
      patient. DATA SOURCES: Published articles and texts on thoracic disorders and CT
      diagnosis. SUMMARY OF REVIEW: In the acutely ill patient with complex pulmonary
      and cardiac disorders a thoracic CT can be useful in determining the cardiac,
      pulmonary, pleural and mediastinal abnormalities present. With an understanding
      of the position and appearance of normal intrathoracic structures (and artifacts)
      acute thoracic disorders can be easily assessed by the non-radiologist,
      facilitating the correct diagnosis and the appropriate management. CONCLUSIONS:
      Thoracic CT offers the intensive care specialist the option of evaluating the
      pulmonary system, pleura, mediastinum, heart, pericardium, and aorta where plain
      radiographs are often inadequate. New mobile CT technology offers CT to patients
      confined to the intensive care unit due to haemodynamic instability.

PMID- 16573515
TI  - Termination of ventricular tachycardia after methoxamine.
AB  - A case of ventricular tachycardia which reverted with intravenous methoxamine is
      presented. The methoxamine was used to increase blood pressure during anaesthesia
      for direct current cardioversion. While alpha adrenergic agonists have been used
      previously to increase vagal tone via a baroreceptor mechanism to revert
      supraventricular tachycardias, this is the first case where a sustained
      ventricular tachycardia reverted with an alpha adrenergic agonist. The mechanisms
      likely to have caused the reversion are discussed.

PMID- 16573516
TI  - Important unusual infections in Australia: a critical care perspective.
AB  - OBJECTIVE: To review a number of the important unusual infections in Australia
      that can lead to critical illness. DATA SOURCES: Articles, reports and published
      reviews on Japanese encephalitis, murine typhus, Australian spotted fever,
      Australian bat lyssavirus, leptospirosis, Capnocytophaga canimorsus,
      Chromobacterium violaceum, Edwardsiella tarda and Vibriosis. Emphasis was placed
      on articles, reports and published reviews published between 1990-2001. SUMMARY
      OF REVIEW: Japanese encephalitis has recently emerged in Australia, with reported
      outbreaks in the Torres Strait and north Queensland. Murine typhus needs to be
      included in the differential diagnosis of a patient with fever, headache and
      rash, especially if there has been possible exposure to rats and/or their
      droppings. If the symptoms follow exposure to ticks, or following a known tick
      bite, then Australian spotted fever needs to be considered. Australian bat
      lyssavirus can cause a fatal rabies-like disease in humans exposed to infection
      by bites or scratches from bats. Leptospirosis should be suspected in any patient
      with an appropriate history of exposure (especially occupational) and a history
      of myalgia, arthralgia, fever, malaise and/or chest X-ray shadowing.
      Capnocytophaga should be specifically sought in any patient with fever and/or
      septicaemia following a dog bite, especially if immunocompromised. Along with
      melioidosis, Chromobacteriosis should be considered in the differential diagnosis
      of a rapidly progressing septic illness with skin lesions and/or multiple
      visceral abscesses in a patient exposed to soil or muddy water. Edwardsiella
      ought to be considered as the causative agent of a soft tissue infection, septic
      arthritis or septicaemia in a recreational fisher or swimmer, especially if
      following a marine puncture wound. If the exposure is related to salty or
      brackish water, then Vibriosis needs to be considered. Vibriosis should also be
      suspected in a patient with septicaemia and a history of recent ingestion of raw
      or under-cooked seafood, especially oysters. CONCLUSIONS: Critical care
      physicians need to remain alert to unusual infectious agents as many can lead to
      significant morbidity and are associated with a high mortality rate.

PMID- 16573517
TI  - The pro-con debate: educational, or just another blood sport?

PMID- 16573518
TI  - A 22 year old man admitted to intensive care with hyperthermia and seizures.

PMID- 16573519
TI  - God, medicine and ethics.

PMID- 16573520
TI  - Characterization of COMMD protein-protein interactions in NF-kappaB signalling.
AB  - COMMD [copper metabolism gene MURR1 (mouse U2af1-rs1 region 1) domain] proteins
      constitute a recently identified family of NF-kappaB (nuclear factor kappaB)
      inhibiting proteins, characterized by the presence of the COMM domain. In the
      present paper, we report detailed investigation of the role of this protein
      family, and specifically the role of the COMM domain, in NF-kappaB signalling
      through characterization of protein-protein interactions involving COMMD
      proteins. The small ubiquitously expressed COMMD6 consists primarily of the COMM
      domain. Therefore COMMD1 and COMMD6 were analysed further as prototype members of
      the COMMD protein family. Using specific antisera, interaction between endogenous
      COMMD1 and COMMD6 is described. This interaction was verified by independent
      techniques, appeared to be direct and could be detected throughout the whole
      cell, including the nucleus. Both proteins inhibit TNF (tumour necrosis factor)
      induced NF-kappaB activation in a non-synergistic manner. Mutation of the amino
      acid residues Trp24 and Pro41 in the COMM domain of COMMD6 completely abolished
      the inhibitory effect of COMMD6 on TNF-induced NF-kappaB activation, but this was
      not accompanied by loss of interaction with COMMD1, COMMD6 or the NF-kappaB
      subunit RelA. In contrast with COMMD1, COMMD6 does not bind to IkappaBalpha
      (inhibitory kappaBalpha), indicating that both proteins inhibit NF-kappaB in an
      overlapping, but not completely similar, manner. Taken together, these data
      support the significance of COMMD protein-protein interactions and provide new
      mechanistic insight into the function of this protein family in NF-kappaB
      signalling.

PMID- 16573521
TI  - Regulation of prokaryotic adenylyl cyclases by CO2.
AB  - The Slr1991 adenylyl cyclase of the model prokaroyte Synechocystis PCC 6803 was
      stimulated 2-fold at 20 mM total C(i) (inorganic carbon) at pH 7.5 through an
      increase in k(cat). A dose response demonstrated an EC50 of 52.7 mM total C(i) at
      pH 6.5. Slr1991 adenylyl cyclase was activated by CO2, but not by HCO3-. CO2
      regulation of adenylyl cyclase was conserved in the CyaB1 adenylyl cyclase of
      Anabaena PCC 7120. These adenylyl cyclases represent the only identified
      signalling enzymes directly activated by CO2. The findings prompt an urgent
      reassessment of the activating carbon species for proposed HCO3--activated
      adenylyl cyclases.

PMID- 16573522
TI  - Mapping QTLs on chicken chromosome 1 for performance and carcass traits in a
      broiler x layer cross.
AB  - With the objective of mapping quantitative trait loci (QTLs) for performance and
      carcass traits, an F2 chicken population was developed by crossing broiler and
      layer lines. A total of 2063 F2 chicks in 21 full-sib families were reared as
      broilers and slaughtered at 42 days of age. Seventeen performance and carcass
      traits were measured. Parental F(0) and F1 individuals were genotyped with 80
      microsatellites from chicken chromosome 1 to select informative markers. Thirty
      three informative markers were used for selective genotyping of F2 individuals
      with extreme phenotypes for body weight at 42 days of age (BW42). Based on the
      regions identified by selective genotyping, seven full-sib families (649 F2
      chicks) were genotyped with 26 markers. Quantitative trait loci affecting body
      weight, feed intake, carcass weight, drums and thighs weight and abdominal fat
      weight were mapped to regions already identified in other populations.
      Quantitative trait loci for weights of gizzard, liver, lungs, heart and feet, as
      well as length of intestine, not previously described in the literature were
      mapped on chromosome 1. This F2 population can be used to identify novel QTLs and
      constitutes a new resource for studies of genes related to growth and carcass
      traits in poultry.

PMID- 16573523
TI  - Assessing genetic diversity in indigenous Veneto chicken breeds using AFLP
      markers.
AB  - Genetic variation in four indigenous chicken breeds from the Veneto region of
      Italy was assessed using amplified fragment length polymorphism (AFLP) markers. A
      total of 99 individuals were analysed using three AFLP primer combinations that
      produced 70 polymorphisms. Four indigenous Veneto chicken breeds (Ermellinata,
      Padovana, Pepoi and Robusta) and a reference broiler line were included in the
      analysis. Breed-specific markers were identified in each breed. The expected
      heterozygosity did not differ significantly among the indigenous Veneto chicken
      breeds and the broiler line. The coefficient of gene variation (Gst) value across
      loci indicated that almost half of the total variability was observed among
      breeds. Nei's standard genetic distance between pairs of breeds showed that the
      distance between the broiler line and the Pepoi breed was greater than the
      distances between the broiler line and the other three chicken breeds. Cluster
      analysis based on standard genetic distances between breeds indicated that the
      Padovana and Pepoi breeds were closely related. Factorial analysis based on a
      binary matrix of the AFLP data showed a clear distinction of all breeds.

PMID- 16573524
TI  - Identification of quantitative trait loci associated with egg quality, egg
      production, and body weight in an F2 resource population of chickens.
AB  - Egg production and egg quality are complex sex-limited traits that may benefit
      from the implementation of marker-assisted selection. The primary objective of
      the current study was to identify quantitative trait loci (QTL) associated with
      egg traits, egg production, and body weight in a chicken resource population.
      Layer (White Leghorn hens) and broiler (Cobb-Cobb roosters) lines were crossed to
      generate an F2 population of 508 hens over seven hatches. Phenotypes for 29
      traits (weekly body weight from hatch to 6 weeks, egg traits including egg,
      albumen, yolk, and shell weight, shell thickness, shell puncture score,
      percentage of shell, and egg shell colour at 35 and 55 weeks of age, as well as
      egg production between 16 and 55 weeks of age) were measured in hens of the
      resource population. Genotypes of 120 microsatellite markers on 28 autosomal
      groups were determined, and interval mapping was conducted to identify putative
      QTL. Eleven QTL tests representing two regions on chromosomes 2 and 4 surpassed
      the 5% genome-wise significance threshold. These QTL influenced egg colour, egg
      and albumen weight, percent shell, body weight, and egg production. The
      chromosome 4 QTL region is consistent with multiple QTL studies that define
      chromosome 4 as a critical region significantly associated with a variety of
      traits across multiple resource populations. An additional 64 QTL tests surpassed
      the 5% chromosome-wise significance threshold.

PMID- 16573525
TI  - High-resolution physical mapping and construction of a porcine contig spanning
      the intramuscular fat content QTL.
AB  - We previously mapped a locus for porcine intramuscular fat content (IMF) by
      linkage analysis to a 17.1-cM chromosome interval on Sus scrofa chromosome 7
      (SSC7) flanked by microsatellite markers SW1083 and SW581. In this study, we
      identified 34 microsatellite markers and 14 STSs from the 17.1-cM IMF
      quantitative trait loci (QTL) region corresponding to HSA14q and aligned those
      loci using the INRA-University of Minnesota porcine radiation hybrid (IMpRH)
      panel. We then constructed a 5.2-Mb porcine bacterial artificial chromosome (BAC)
      contig of this region that was aligned using the RH panel. Finally, the IMF QTL
      was fine-mapped to 12.6 cM between SJ169 and MM70 at the 0.1% chromosome-wise
      significance level by genotyping the previously studied F2 resource family with
      17 additional microsatellites. We also demonstrated that the SJ169-MM70 interval
      spans approximately 3.0 Mb and contains at least 12 genes: GALC, GPR65, KCNK10,
      SPATA7, PTPN21, FLJ11806, EML5, TTC8, CHES1, CAP2P1, CHORDC2P and C14orf143.

PMID- 16573526
TI  - Comparative analysis of the bovine MHC class IIb sequence identifies inversion
      breakpoints and three unexpected genes.
AB  - The bovine major histocompatibility complex (MHC) or BoLA is organized
      differently from typical mammalian MHCs in that a large portion of the class II
      region, called class IIb, has been transposed to a position near the centromere
      on bovine chromosome 23. Gene mapping indicated that the rearrangement resulted
      from a single inversion, but the boundaries and gene content of the inverted
      segment have not been fully determined. Here, we report the genomic sequence of
      BoLA IIb. Comparative sequence analysis with the human MHC revealed that the
      proximal inversion breakpoint occurred approximately 2.5 kb from the 3' end of
      the glutamate-cysteine ligase, catalytic subunit (GCLC) locus and that the distal
      breakpoint occurred about 2 kb from the 5' end from a divergent class IIDRbeta
      like sequence designated DSB. Gene content, order and orientation of BoLA IIb are
      consistent with the single inversion hypothesis when compared with the
      corresponding region of the human class II MHC (HLA class II). Differences with
      HLA include the presence of a single histone H2B gene located between the
      proteasome subunit, beta type, 9 (PSMB9) and DMB loci and a duplicated TAP2 with
      a variant splice site. BoLA IIb spans approximately 450 kb DNA, with 20
      apparently intact genes and no obvious pseudogenes. The region contains 227
      simple sequence repeats (SSRs) and approximately 167 kb of retroviral-related
      repetitive DNA. Nineteen of the 20 genes identified in silico are supported by
      bovine EST data indicating that the functional gene content of BoLA IIb has not
      been diminished because it has been transposed from the remainder of BoLA genes.

PMID- 16573527
TI  - Using the chicken genome sequence in the development and mapping of genetic
      markers in the turkey (Meleagris gallopavo).
AB  - The efficacy of employing the chicken genome sequence in developing genetic
      markers and in mapping the turkey genome was studied. Eighty previously
      uncharacterized microsatellite markers were identified for the turkey using BLAST
      alignment to the chicken genome. The chicken sequence was then used to develop
      primers for polymerase chain reaction where the turkey sequence was either
      unavailable or insufficient. A total of 78 primer sets were tested for
      amplification and polymorphism in the turkey, and informative markers were
      genetically mapped. Sixty-five (83%) amplified turkey genomic DNA, and 33 (42%)
      were polymorphic in the University of Minnesota/Nicholas Turkey Breeding Farms
      mapping families. All but one marker genetically mapped to the position predicted
      from the chicken genome sequence. These results demonstrate the usefulness of the
      chicken sequence for the development of genomic resources in other avian species.

PMID- 16573528
TI  - Genome-wide linkage disequilibrium in two Japanese beef cattle breeds.
AB  - There is little knowledge about the degree of linkage disequilibrium (LD) in beef
      cattle. This study aims to perform a genome-wide search for LD in Japanese Black
      and Japanese Brown beef cattle and to compare the level of LD between these two
      breeds. Parameter D' (the LD coefficient) was used as a measure of LD, and LD was
      tested for significance of allelic associations between syntenic and between non
      syntenic marker pairs. Effects of breed, chromosome, genetic map distance and
      their interactions with D' were tested based on least squares analyses. Both
      breeds showed high levels of LD, which ranged over several tens of cM and
      declined as the marker distance increased for syntenic marker pairs. A rapid
      decline of the D' value was observed between markers that were spaced 5 and 20 cM
      apart. LD was significant in most cases for marker pairs <40 cM apart but was not
      significant between non-syntenic loci. The pattern of LD found in these two
      breeds was similar to that previously published for dairy cattle. The D' value
      between breeds was not significantly different (P > 0.05), but the interaction
      between breed and chromosome was highly significant (P < 0.001). Genetic
      selection seems to have caused the heterogeneity of the D' values among
      chromosomes within breed. These results indicate that LD mapping is a useful tool
      for fine-mapping quantitative trait loci of economically important traits in
      Japanese beef cattle.

PMID- 16573529
TI  - Construction of a medium-density horse gene map.
AB  - A medium-density map of the horse genome (Equus caballus) was constructed using
      genes evenly distributed over the human genome. Three hundred and twenty-three
      exonic primer pairs were used to screen the INRA and the CHORI-241 equine BAC
      libraries by polymerase chain reaction and by filter hybridization respectively.
      Two hundred and thirty-seven BACs containing equine gene orthologues, confirmed
      by sequencing, were isolated. The BACs were localized to horse chromosomes by
      fluorescent in situ hybridization (FISH). Overall, 165 genes were assigned to the
      equine genomic map by radiation hybrid (RH) (using an equine RH(5000) panel)
      and/or by FISH mapping. A comparison of localizations of 713 genes mapped on the
      horse genome and on the human genome revealed 59 homologous segments and 131
      conserved segments. Two of these homologies (ECA27/HSA8 and ECA12p/HSA11p) had
      not been previously identified. An enhanced resolution of conserved and
      rearranged chromosomal segments presented in this study provides clarification of
      chromosome evolution history.

PMID- 16573530
TI  - Genome-wide identification of quantitative trait loci in a cross between
      Hampshire and Landrace I: carcass traits.
AB  - We report the identification of quantitative trait loci (QTL) affecting carcass
      composition, carcass length, fat deposition and lean meat content using a genome
      scan across 462 animals from a combined intercross and backcross between
      Hampshire and Landrace pigs. Data were analysed using multiple linear regression
      fitting additive and dominance effects. This model was compared with a model
      including a parent-of-origin effect to spot evidence of imprinting. Several
      precisely defined muscle phenotypes were measured in order to dissect body
      composition in more detail. Three significant QTL were detected in the study at
      the 1% genome-wide level, and twelve significant QTL were detected at the 5%
      genome-wide level. These QTL comprise loci affecting fat deposition and lean meat
      content on SSC1, 4, 9, 10, 13 and 16, a locus on SSC2 affecting the ratio between
      weight of meat and bone in back and weight of meat and bone in ham and two loci
      affecting carcass length on SSC12 and 17. The well-defined phenotypes in this
      study enabled us to detect QTL for sizes of individual muscles and to obtain
      information of relevance for the description of the complexity underlying other
      carcass traits.

PMID- 16573531
TI  - White spotting in the domestic cat (Felis catus) maps near KIT on feline
      chromosome B1.
AB  - Five feline-derived microsatellite markers were genotyped in a large pedigree of
      cats that segregates for ventral white spotting. Both KIT and EDNRB cause similar
      white spotting phenotypes in other species. Thus, three of the five
      microsatellite markers chosen were on feline chromosome B1 in close proximity to
      KIT; the other two markers were on feline chromosome A1 near EDNRB. Pairwise
      linkage analysis supported linkage of the white spotting with the three
      chromosome B1 markers but not with the two chromosome A1 markers. This study
      indicates that KIT, or another gene within the linked region, is a candidate for
      white spotting in cats. Platelet-derived growth factor alpha (PDGFRA) is also a
      strong candidate, assuming that the KIT-PDGFRA linkage group, which is conserved
      in many mammalian species, is also conserved in the cat.

PMID- 16573532
TI  - Characterization of OCA2 cDNA in different porcine breeds and analysis of its
      potential effect on skin pigmentation in a red Iberian strain.
AB  - Although the function of the OCA2 gene product has not been totally clarified,
      variation in OCA2 has been associated with skin and hair pigmentation in human
      and mouse. However, its contribution to skin colour in domestic species has not
      been reported. In this study, cDNA and intron 9 sequences of the porcine OCA2
      gene have been characterized in several pig populations. The cDNA sequence
      alignment of 20 animals from eight porcine populations allowed the identification
      of 10 single nucleotide polymorphisms (SNPs); five of the 10 SNPs were non
      synonymous. The intron 9 sequence alignment of 12 animals belonging to four pig
      populations revealed four additional SNPs. Skin colour variation was analysed in
      a red strain of Iberian pigs with segregation of three SNPs forming two OCA2
      intragenic haplotypes. Results from this study provide evidence of a suggestive
      dominant effect of haplotypes on colour intensity and indicate an important
      contribution of additive polygenic effects (h2 = 0.56 +/- 0.21) to the variance
      of this trait.

PMID- 16573533
TI  - Sequence diversity and rates of molecular evolution between sheep and cattle
      genes.
AB  - Experiments that aim to identify genes of importance in sheep are currently
      inhibited by a paucity of genomic resources. One approach, therefore, is to
      exploit the wealth of data and associated capabilities becoming available for the
      bovine genome. Cross-species application of microarrays and comparative
      sequencing to identify single nucleotide polymorphisms are two possibilities;
      however, both are dependant on the level of nucleotide sequence similarity
      between the two species. This study used 120 gene orthologues consisting of over
      60 kb of aligned sequence to estimate the gene diversity between cattle and
      sheep. Less than 3% of protein-coding nucleotide positions were found to be
      different, indicating that the prospect for successfully using cross-species
      strategies is high. Substitution at synonymous sites ranged between 6.9 and 7.7%
      (+/- 0.3%), and was higher than at non-synonymous sites (1.4-1.7 +/- 0.1%). The
      relative rate test was used to determine whether the observed mutation rates were
      constant between the two lineages. While the rate at synonymous sites appeared
      constant, the rate at non-synonymous sites was significantly higher within the
      caprinae lineage (sheep) when compared with bovinae (cattle; chi2 = 10.03; d.f. =
      1, P < 0.01). This is the first demonstration that variable rates of molecular
      evolution may be present within the family Bovidae.

PMID- 16573534
TI  - Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR)
      mutation.
AB  - Albino phenotypes are documented in a variety of species including the domestic
      cat. As albino phenotypes in other species are associated with tyrosinase (TYR)
      mutations, TYR was proposed as a candidate gene for albinism in cats. An Oriental
      and Colourpoint Shorthair cat pedigree segregating for albinism was analysed for
      association with TYR by linkage and sequence analyses. Microsatellite FCA931,
      which is closely linked to TYR and TYR sequence variants were tested for
      segregation with the albinism phenotype. Sequence analysis of genomic DNA from
      wild-type and albino cats identified a cytosine deletion in TYR at position 975
      in exon 2, which causes a frame shift resulting in a premature stop codon nine
      residues downstream from the mutation. The deletion mutation in TYR and an allele
      of FCA931 segregated concordantly with the albino phenotype. Taken together, our
      results suggest that the TYR gene corresponds to the colour locus in cats and its
      alleles, from dominant to recessive, are as follows: C (full colour) > c(b)
      (burmese) > or = c(s) (siamese) > c (albino).

PMID- 16573536
TI  - W-specific microsatellite loci detected by in silico analysis map to chromosome Z
      of the chicken genome.

PMID- 16573535
TI  - Genetic evidence for the origin of an IGF2 quantitative trait nucleotide in
      Chinese pigs.

PMID- 16573537
TI  - Radiation hybrid mapping and sequence analysis of 21 genes on porcine chromosome
      15.

PMID- 16573538
TI  - Radiation hybrid mapping of genes showing intramuscular fat deposition-associated
      expression changes in bovine musculus longissimus muscle.

PMID- 16573539
TI  - Isolation and characterization of 79 microsatellite markers from the American
      mink (Mustela vison).

PMID- 16573540
TI  - Management of patients with post-transplant lymphoproliferative disorder: the
      role of rituximab.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of
      solid organ and bone marrow transplantations. Rituximab (Rituxan, Mabthera), a
      chimeric monoclonal antibody to the CD20 antigen on the surface of B-cell
      lymphocytes, has been used increasingly in the treatment of PTLD. Rituximab was
      initially approved for the treatment of low-grade non-Hodgkin lymphomas, but
      multiple case studies, retrospective analyses, and phase II trials demonstrate
      the benefit of rituximab in PTLD. This paper reviews the current data on
      rituximab and its promising role in the management of PTLD.

PMID- 16573541
TI  - Liver allocation: the intent-to-treat approach.

PMID- 16573542
TI  - Is MELD score sufficient to predict not only death on waiting list, but also post
      transplant survival?
AB  - Model for end-stage liver disease (MELD) score has emerged as a useful tool in
      predicting mortality in patients awaiting liver transplantation. There is still,
      however, discussion as to whether further parameters could improve the
      sensitivity and specificity of the MELD score. From 1997 to 2003, 621 adult
      patients with end-stage liver disease were listed for orthotopic liver
      transplantation (OLT). Patients suffering from hepatoma were excluded from
      analysis (113 patients). The MELD score was investigated at the time of listing
      (MELD ON) and of coming off the list (MELD OFF). Patients who died while on the
      waiting list showed a significant increase in their MELD score during the waiting
      time (MELD ON: 21 +/- 7 vs. MELD OFF: 28 +/- 9) as well as a significantly higher
      MELD ON compared with patients who were transplanted (MELD ON: 16 +/- 5 vs. MELD
      OFF: 17 +/- 7) or removed from the waiting list (MELD ON: 16 +/- 6 vs. MELD OFF:
      12 +/- 3). Multivariate analysis identified MELD ON, ascites and recurrent
      infection as independent risk factors for death on the waiting list (P < 0.01).
      MELD score was not identified as a predictor for the post-transplant survival
      rate. MELD score is a strong predictor for death on the waiting list, but
      refractory ascites and recurrent infection are independent risk factors, too.

PMID- 16573543
TI  - An outcome comparison between primary liver transplantation and retransplantation
      based on the pretransplant MELD score.
AB  - Survival after liver retransplantation (RLTX) is worse than after primary liver
      transplantation (LTX). We studied retrospectively the 2-year outcome in 44
      patients who received RLTX more than 30 days after the primary transplant and in
      669 after LTX performed between December 1993 and October 1999, focusing on the
      relation between the model for end-stage liver disease (MELD) score immediately
      pretransplant and post-transplant survival. A 2-year survival for RLTX was
      inferior to LTX (65.9% vs. 82.9%, P < or = 0.01). This difference was greatest
      with MELD scores < 25; survival within 2 years remained 11.3-18.2% less for RLTX
      than for LTX (6 months, P = 0.002; 12 months, P = 0.029, 24 months, P = 0.123).
      Mortality was mainly related to early vascular complications and sepsis. Two-year
      survival after RLTX was 81.8% if RLTX occurred < 2 years after LTX and 50% if the
      interval between LTX and RLTX was > 2 years (P < 0.05). MELD scores were similar
      in 2-year survivors and nonsurvivors after late RLTX (P = 0.82). Late RLTX is
      marked by poor survival regardless of the pretransplant MELD score. The MELD
      based allocation system may not benefit patients who undergo retransplantation.

PMID- 16573544
TI  - A prospective, randomized, multi-centre trial of systemic adjuvant chemotherapy
      versus no additional treatment in liver transplantation for hepatocellular
      carcinoma.
AB  - The role of adjuvant systemic chemotherapy in liver transplantation (LT) for
      hepatocellular carcinoma (HCC) is controversial. Here, we report the results of a
      Nordic prospective, randomized, multi-centre trial of systemic low-dose
      doxorubicin in patients with HCC. Between February 1996 and April 2004, 46
      patients were randomized to receive either neoadjuvant doxorubicin in combination
      with LT (chemo group; n = 19) or LT alone (control group; n = 27). In the chemo
      group, doxorubicin was administered intravenously, 10 mg/m(2) weekly, starting
      from acceptance onto the waiting list for LT. One intraoperative dose of 15
      mg/m(2) was given, and postoperatively doxorubicin was given weekly at a dose of
      10 mg/m(2), depending on the clinical course, up to a cumulative dose of 400
      mg/m(2). Actuarial, 3-year overall survival (OS) and disease-free survival (DFS)
      in the control group were 70% and 50%, respectively. In the chemo group, both OS
      and DFS were 63%. Freedom from recurrence at 3 years was 55% in the control group
      and 74% in the chemo group. None of the differences was statistically
      significant. Neoadjuvant treatment with systemic low-dose doxorubicin seems not
      to improve either survival or freedom from recurrence in patients with HCC
      undergoing LT.

PMID- 16573545
TI  - Simultaneous corticosteroid avoidance and calcineurin inhibitor minimization in
      renal transplantation.
AB  - Steroids and calcineurin inhibitors (CNI) have been mainstays of
      immunosuppression but both have numerous side effects that are associated with
      substantial morbidity and mortality. This study was carried out to determine if
      steroids can be eliminated with early discontinuation of cyclosporine A (CsA) and
      later discontinuation of mycophenolate mofetil (MMF). Ninety-six patients with
      kidney transplants were entered into four subgroups of two pilot studies. All
      patients received Thymoglobulin induction, rapamycin (RAPA), and the
      immunonutrients arginine and an oil containing omega-3 fatty acids. Mycophenolate
      mofetil was started in standard doses and discontinued by 2 years. CsA was given
      in reduced doses for either 4, 6, or 12 months. Follow-up was 12-36 months.
      Thirteen first rejection episodes occurred during the first year (14%). Combining
      all patients, 86% were rejection-free at 1 year, 80% at 2 years and 79% at 3
      years. No kidney has been lost to acute rejection. Ninety percent of the 84
      patients at risk at the end of the study were steroid-free and 87% were off CNI.
      Fifty-seven percent of 54 patients with a functioning kidney at 3 years were
      receiving monotherapy with RAPA. We conclude that this therapeutic strategy is
      worthy of a prospective multi-center clinical trial.

PMID- 16573547
TI  - Sirolimus and FK778: a comparison of two anti-proliferative immunosuppressants
      for prevention of experimental obliterative airway disease.
AB  - This study examined the efficacies of sirolimus and the novel immunosuppressive
      agent FK778 to prevent obliterative airway disease (OAD). Tracheae from Brown
      Norway donors were heterotopically transplanted in the greater omentum of Lewis
      rats. Recipients were treated for 28 days with sirolimus (0.5 or 2 mg/kg), FK778
      (5 or 20 mg/kg), or combination regimens (0.5 + 5 mg/kg, 2 + 20 mg/kg). Tracheal
      segments were evaluated for degree of luminal obliteration, percentage of luminal
      epithelial cell coverage, and peritracheal infiltration. In vitro smooth muscle
      cell (SMC) proliferation and migration assays were performed to assess direct
      nonimmune-related effects of the drugs. Sirolimus 2 mg/kg and FK778 20 mg/kg
      effectively reduced graft infiltration and prevented airway obliteration, whereas
      FK778 5 mg/kg was insufficient. Sirolimus 0.5 mg/kg at least showed moderate
      inhibitory effects on luminal obliteration and graft infiltration. Combination
      regimens revealed no significant beneficial effects. Both sirolimus and FK778
      barely showed preserved epithelial coverage. Within the range of relevant
      concentrations, FK778 showed more potent anti-proliferative and anti-migratory
      effects on SMC in vitro than sirolimus. Both agents proved effective to prevent
      OAD development without preserving relevant amounts of epithelium. The anti
      proliferative potency on SMCs seems to be an especially important mechanism for
      FK778. De novo combination regimens revealed no beneficial interaction and thus
      remain doubtful.

PMID- 16573546
TI  - 24-h storage of pig livers in UW, HTK, hydroxyethyl starch, and saline solution:
      is microdialysis an appropriate method for the continuous graft monitoring during
      preservation?
AB  - Recent studies demonstrate the feasibility of microdialysis to monitor metabolism
      in ischemic livers. Whether these parameters correlate with markers of liver cell
      integrity in an experimental model using pig livers and different preservation
      solutions was an aim of this study. Pig livers were flushed with either 4 degrees
      C Histidine-Typtophan-Ketoglutarate solution (HTK) (Custodiol), University of
      Wisconsin solution (ViaSpan), and hydroxyethyl starch, or 12 degrees C saline
      solution. After 24-h storage, the livers were rinsed with saline to measure liver
      enzymes and lactate from the effluate. Utilizing microdialysis, intraparenchymal
      lactate, pyruvate, glucose, and glycerol was monitored. Tissue biopsies were
      taken for histological examinations. Cold preservation resulted in a decrease of
      metabolic activity measured by intrahepatic glucose, lactate, and pyruvate
      levels, as well as lactate in the effluate, independently of the solution used.
      Of particular interest, glycerol levels partially reflected the extent of
      hepatocellular damage and liver enzyme release. Glycerol levels partially
      discriminated preservation of different quality and were in accordance to
      histological findings and liver enzyme release. Lactate, pyruvate, and glucose
      levels were not appropriate as markers during cold storage. Whether or not
      glycerol monitoring could represent an additional and rational complementation to
      the current practice of macroscopic, microscopic and donor evaluation has to be
      clarified by further studies.

PMID- 16573548
TI  - The down-regulation of IL1alpha and IL6, in monocytes exposed to extracorporeal
      photopheresis (ECP)-treated lymphocytes, is not dependent on lymphocyte
      phosphatidylserine externalization.
AB  - Extracorporeal photopheresis (ECP) has been successfully used to treat some
      inflammatory conditions. Following ECP, lymphocytes become apoptotic and
      untreated monocytes, exposed to post-ECP lymphocytes, reduce proinflammatory
      cytokine secretion. This study attempted to establish if this monocyte
      immunosuppression was linked to phosphatidylserine externalization (detected
      using Annexin V) on the apoptotic lymphocytes. Using density gradient and
      magnetic separation, lymphocytes were isolated from three cutaneous T-cell
      lymphoma and nine chronic graft versus host disease (cGvHD) patients pre-ECP and
      prior to re-infusion (post-ECP). The collected lymphocytes were cultured
      overnight and Annexin V levels determined. Peripheral blood was taken from the
      same patient 20 h later and the monocytes were isolated. The 'fresh' monocytes
      were introduced to each 20 h pre- and post-ECP lymphocyte culture, stimulated
      with lipopolysaccharide (LPS) and Brefeldin A and subsequently tested for
      intracellular tumour necrosis factor alpha, interleukin 1 alpha (IL1alpha),
      IL1beta, IL6 and IL8. For cGvHD patients, the relative levels of IL1alpha and IL6
      were reduced in the untreated, LPS-stimulated monocytes exposed to post-ECP
      lymphocytes. However, the down-regulation of IL1alpha and IL6 did not correlate
      to levels of Annexin V-positive lymphocytes. ECP-treated lymphocytes can reduce
      the ability of LPS-stimulated monocytes to produce some proinflammatory
      cytokines; however, this effect is not dependent on phosphatidylserine
      externalization.

PMID- 16573549
TI  - Intermittent capillary perfusion in rat pancreas grafts following short- and long
      term preservation in University of Wisconsin solution.
AB  - In pancreas transplantation (PTx), ischemia/reperfusion-induced deterioration of
      graft-microcirculation is accompanied by alterations of intermittent capillary
      perfusion (IP; alternating cessation and resumption of capillary blood flow) is
      known to counteract malperfusion. Incidence and effectiveness of IP following
      short- versus long-term preservation of pancreas grafts with University of
      Wisconsin (UW) solution has not been examined so far. PTx was performed in Lewis
      rats following 2-h or 18-h preservation in UW solution. Using intravital
      fluorescence microscopy, functional capillary density (FCD), red blood cell (RBC)
      velocity, IP-incidence and -frequency were analyzed. Laser Doppler flowmetry
      allowed for the determination of erythrocyte flux and velocity. Measurements were
      performed at 30, 60 and 120 min after reperfusion. Nontransplanted animals served
      as controls. FCD, RBC-velocity and -flux remained unchanged in the 2-h group. IP
      was encountered in 87% of all observation areas at 120 min. After 18-h ischemia,
      FCD was significantly reduced, which was paralleled by a 50% incidence of IP at
      120 min. Tissue edema and leukocyte infiltration in pancreas grafts following 18
      h preservation were significantly enhanced. Therefore, IP is an important
      mechanism aimed at improving microcirculation and UW solution is suitable to
      preserve vasomotion-activities enabling long-term preservation in a pancreas
      graft.

PMID- 16573551
TI  - EBV-associated recurrent Hodgkin's disease after renal transplantation.
AB  - Hodgkin's disease is recognized as part of the spectrum of post-transplantation
      lymphoproliferative disorders (PTLD), although it is still an uncommon de novo
      malignancy in this population. Epstein-Barr virus (EBV) has been linked to both
      post-transplant non-Hodgkin's lymphomas and Hodgkin's disease. We report a case
      of recurrent Hodgkin's disease in a patient who received a renal transplant in
      childhood and later developed EBV-associated Hodgkin's disease with remission
      after chemotherapy until subsequent relapse 9 years later that was successfully
      treated. To our knowledge, this is the first report of recurrent Hodgkin's
      disease in a transplant recipient. We briefly discuss the pathogenesis of and
      risk factors for EBV-related PTLD, utility of EBV load surveillance, and the
      options for treatment of PTLD including immunosuppression reduction, antiviral
      therapy, anti-CD20 monoclonal antibodies, cytotoxic T cells, and the possible
      roles of interferon-alpha and rapamycin.

PMID- 16573550
TI  - Changes in endothelial function before and after renal transplantation.
AB  - Endothelial dysfunction is an early key event in the development of
      atherosclerotic cardiovascular disease observed in chronic renal failure
      patients. The role of renal transplantation (RTx) on endothelial dysfunction is
      still unclear. The aim of this study was to evaluate the endothelial function of
      chronic renal failure patients before RTx (while they were on hemodialysis, HD),
      and after RTx (at the 6th and 12th months) by a noninvasive method, brachial
      arterial ultrasound. A total of 22 (17 male, mean age: 33.9 +/- 11.6 years) RTx
      recipients were enrolled in the study. Endothelium-dependent vasodilation (EDD)
      was assessed by establishing reactive hyperemia. EDD prior to transplantation was
      significantly lower when compared with EDD measured at the 6th and 12th months
      after RTx (EDD pretransplantation: 6 +/- 3.7%, EDD at the 6th month of RTx: 8.3
      +/- 2.3% and EDD at the 12th month of RTx: 12.1 +/- 3.6%, P < 0.001). When the
      EDD values measured at the 6th and 12th months of RTx were compared, measurements
      of the 12th month were found significantly higher than those of the 6th month (P
      < 0.001). Our results also showed that RTx has provided improvement in
      endothelial function by eliminating the uremic environment although not in the
      early post-RTx period.

PMID- 16573552
TI  - Prednisolone noncompliance and outcome in liver transplant recipients.

PMID- 16573553
TI  - Liver transplantation represents the optimal treatment for fulminant hepatic
      failure from Amanita phalloides poisoning.

PMID- 16573555
TI  - Regulation of MHC class II expression, a unique regulatory system identified by
      the study of a primary immunodeficiency disease.
AB  - Major histocompatibility complex class II (MHC-II) molecules are of central
      importance for adaptive immunity. Defective MHC-II expression causes a severe
      immunodeficiency disease called bare lymphocyte syndrome (BLS). Studies of the
      molecular defects underlying BLS have been pivotal for characterization of the
      regulatory system controlling the transcription of MHC-II genes. The precisely
      controlled pattern of MHC-II gene expression is achieved by a very peculiar and
      highly specialized molecular machinery that involves the interplay between
      ubiquitous DNA-binding transcription factors and a highly unusual, tightly
      regulated, non-DNA-binding coactivator called the MHC class II transactivator
      (CIITA). CIITA single handedly coordinates practically all aspects of MHC-II gene
      regulation and has therefore been dubbed the master controller of MHC-II
      expression. Several of the unusual features of the MHC-II regulatory system may
      be a consequence of the fact that CIITA originated from an ancient family of
      cytoplasmic proteins involved in inflammation and innate immunity. The function
      of CIITA in transcriptional regulation of MHC-II genes could thus be a recent
      acquisition by an ancestral protein having a role in an unrelated system.

PMID- 16573556
TI  - Antigen-presenting cells expressing glutamate decarboxylase 67 were identified as
      epithelial cells in glutamate decarboxylase 67-GFP knock-in mouse thymus.
AB  - Glutamate decarboxylase (GAD), which has two isoforms, GAD65, and GAD67, is
      responsible for synthesis of the major inhibitory neurotransmitter, gamma
      aminobutyric acid. GAD is expressed predominantly in the central nervous system;
      recent reports suggest that GAD is also expressed in non-neuronal organs
      including the pancreas. In the pancreatic islets, GAD serves as one of the
      autoantigens in type I diabetes mellitus. Recent flow cytometric analyses have
      shown that a variety of self-antigens, including GAD, are ectopically transcribed
      and expressed in particular cell populations of the thymus, although consensus
      concerning the cellular phenotype has not been obtained. The aim of this study
      was to clarify the localization and cellular phenotype of GAD67-expressing cells
      in the thymus at a cellular level with a novel approach using GAD67-green
      fluorescent protein (GFP) knock-in mice, in which GFP is expressed specifically
      in GAD67-positive cells. GFP-positive cells were detected in the thymic medulla
      and were identified as epithelial cells by immunohistochemistry. Almost all GFP
      positive cells were positive for major histocompatibility complex (MHC) class II
      antigen staining and were positive for both cytokeratin and Ulex Europaeus
      Agglutinin I, markers of medullary thymic epithelial cells, but were negative for
      CD11c, Gr-1, and CD45, markers of dendritic cells, macrophages, and B
      lymphocytes, respectively.

PMID- 16573557
TI  - HLA-E and immunobiology of pregnancy.
AB  - Recently, it has been suggested that non-classical antigens such as human
      leukocyte antigen (HLA)-G and HLA-E may interact with KIR receptors of NK cells
      which results into downregulation of immune response and helps in the maintenance
      of pregnancy. In the present study, we have investigated HLA-E polymorphism in
      normal fertile women and recurrent spontaneous aborters to assess the effect of
      HLA-E alleles on the success of pregnancy. Allele E*0101 was found to be
      significantly higher in patients with recurrent spontaneous abortion (chi(2) =
      4.097 and P = 0.0430). Differential expression, peptide affinity, and stability
      of E*0101 may be one of the reasons.

PMID- 16573558
TI  - Investigation of killer cell immunoglobulin-like receptor KIR2DL4 diversity by
      sequence-based typing in Chinese population.
AB  - Human killer cell immunoglobulin-like receptors (KIRs) play an important role in
      controlling natural killer (NK) cell function. Here, polymerase chain reaction
      sequence-based typing (PCR-SBT) procedures identifying alleles of the KIR2DL4
      gene have been established. The method was designed around the specific
      amplification of exon 3 to exon 5 and exon 7 to exon 9 of the KIR2DL4 gene and
      produce discrimination of KIR2DL4 alleles. Genomic DNAs from 83 healthy unrelated
      Chinese Han individuals were typed for KIR2DL4 alleles by this method. Each
      sample was assigned to the putative KIR2DL4 allele combination according to the
      nucleotide polymorphism profiles of all KIR2DL4 alleles. Twenty-one different
      genotypes and seven KIR2DL4 alleles were observed in the population, with
      KIR2DL4*00102 having the highest frequency, 0.5. Five individuals bear a
      recombinant allele KIR3DP*004 that associated with three putative KIR2DL4
      alleles. Our data demonstrated that the established PCR-SBT method for KIR2DL4
      allele typing was reliable, and Chinese Han population is distinct in KIR2DL4
      allele frequencies in comparison to some other populations.

PMID- 16573559
TI  - Optimization of the MhcOvar-DRB1 gene typing.
AB  - The variability of the sheep major histocompatibility complex (MHC) class II DRB1
      locus has been analyzed in this work. Exon 2 of Ovar-DRB1 was amplified by
      polymerase chain reaction (PCR) with the primers designed by Amills et al. for
      goats. In a total of 187 sheep of Latxa breed, we identified by PCR-single-strand
      conformation polymorphism (SSCP) 19 alleles, eight of them previously
      unpublished. Moreover, the observed heterozygosity reached 91-95%. A new allelic
      type named DRB*14 was defined, which brings to light once more the discussion as
      to the ancestor of the domestic sheep. Although all the defined alleles can be
      discriminated by PCR-SSCP, sequence-based typing is proposed as the technique of
      choice for sheep DRB1 gene typing.

PMID- 16573560
TI  - Th1/Th2 cytokine gene polymorphisms in patients with idiopathic pulmonary
      fibrosis.
AB  - We investigated 30 patients with idiopathic pulmonary fibrosis (IPF) and 103
      healthy volunteers for the cytokines polymorphisms of the IL-1alpha, IL-1beta, IL
      1R, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, tumor necrosis factor-alpha,
      interferon-gamma, transforming growth factor-beta, IL-1beta, IL-2, IL-4, and IL
      4RA genes. The strongest correlation of a genotype with the disease was found for
      gene polymorphisms at the promotor region of IL-4, where the CT genotypes at the
      positions (-590) and (-33) were more frequent in the IPF group (P < 0.0001,
      P(corr) < 0.0022; vs P < 0.0001, P(corr) < 0.0022). Our results support the idea
      of the pathogenic role of cytokine gene polymorphisms in the etiology and
      pathogenesis of IPF, with emphasize on the IL-4 promotor gene polymorphisms.

PMID- 16573561
TI  - HLA-B27 testing in Thai patients using the PCR-SSP technique.
AB  - We develop the HLA-B27 test kit using the PCR-SSP technique. Five hundred forty
      blood samples were tested for HLA-B27 by microlymphocytotoxicity test (LCT) and
      PCR-SSP. It was found that 127 (23.5%) and 134 (24.8%) of these samples were
      positive for HLA-B27 by LCT and PCR-SSP, respectively. The sensitivity and
      specificity of the PCR-SSP were 94.8 and 100%, respectively, when using LCT as
      the standard method. The PCR-SSP positive predictive value was 100%, negative
      predictive value was 98.3%, and a concordance rate of 98.7%. This study shows
      that the PCR-SSP is simple, convenient, and a more cost-effective in-house test
      kit.

PMID- 16573562
TI  - HLA-DRB1, -DQB1 alleles in head and neck carcinoma patients.
AB  - Certain HLA class II alleles have been reported to play a role in development or
      prevention of cervical carcinoma, an epithelial malignancy linked to human
      papillomavirus (HPV). In head and neck carcinomas, of which a subset is also HPV
      associated, the impact of HLA genes remains unknown. HLA-DRB1, -DQB1 alleles were
      determined in a comprehensive series of 162 head and neck carcinoma patients, for
      which 83 consecutive cadaveric organ donors of Finnish origin served as controls.
      DRB1*03 was associated with node-negative disease and DRB1*08 and 13 with small
      tumors; DRB1*04 was protective against disease relapse. Most alleles of
      borderline significance in this study act similarly in cervical carcinomas.

PMID- 16573563
TI  - Gene frequencies of human platelet antigens in the Macedonian population.
AB  - Human platelet antigen (HPA) systems consist of more than 12 bi-allelic antigen
      polymorphisms. Due to these polymorphisms, platelet-membrane glycoproteins can be
      recognized as alloantigens or autoantigens and can cause conditions such as
      fetomaternal alloimmune thrombocytopenia, post-transfusion refractoriness to
      platelets, and post-transfusion throbocytopenic purpura. The purpose of this
      study was to investigate the distribution of HPA-1, -2, -3, and -5 in Macedonian
      population by using the polymerase chain reaction and restriction fragment length
      polymorphism. The allele frequencies were 0.865 for HPA-1a, 0.135 for HPA-1b,
      0.852 for HPA-2a, 0.148 for HPA-2b, 0.578 for HPA-3a, 0.422 for HPA-3b, 0.909 for
      HPA-5a, and 0.091 for HPA-5b. Results of our study were not significantly
      different from those reported in the other European studies. Our population
      displayed the highest frequency for HPA-2b allele (0.148) reported among European
      population.

PMID- 16573564
TI  - Identification of a novel HLA-B*44 variant (B*4441) in three unrelated Caucasian
      individuals.
AB  - Here, we report the identification of a new human leukocyte antigen (HLA)-B*44
      allele found almost simultaneous in three DNA samples which were part of routine
      bone marrow donor typing by order of the German registry 'Aktion
      Knochenmarkspende Bayern'. The samples appeared noticeable in different
      polymerase chain reactions using sequence-specific primers (PCR-SSP) or sequence
      specific oligonucleotides (PCR-SSO). Sequence-based typing revealed a novel
      allele officially designated as B*4441*. This sequence differs from HLA
      B*44020101/4427 by two nucleotide positions at the beginning of exon 3: by
      position 353 (T to C) and by position 355 (A to C). These differences in sequence
      result in deviant amino acids at codon 94 (Ile94Thr) and codon 95 (Ile95Leu).

PMID- 16573566
TI  - Sequence analysis of the novel allele HLA-B*070502.

PMID- 16573565
TI  - A new HLA-A allele, A*3113, identified by sequence-based typing in the Chinese
      population.

PMID- 16573567
TI  - Identification of a novel HLA-B*4608 allele in the Chinese population.

PMID- 16573568
TI  - Identification of a novel HLA-B*51 allele, HLA-B*5137, in the Korean population.

PMID- 16573569
TI  - Characterization of a new HLA-DPB1 allele, DPB1*010103.

PMID- 16573570
TI  - Identification of a new HLA-DRB1 variant, DRB1*0451, in the Korean
      populationdagger.

PMID- 16573571
TI  - Nomenclature for factors of the HLA system, update October 2005.

PMID- 16573572
TI  - Nomenclature for factors of the HLA system, update November 2005.

PMID- 16573573
TI  - Nomenclature for factors of the HLA system, update December 2005.

PMID- 16573575
TI  - Epigenetic DNA hypermethylation of the HERP gene promoter induces down-regulation
      of its mRNA expression in patients with alcohol dependence.
AB  - BACKGROUND: Elevated plasma homocysteine concentrations can influence genomic and
      gene-specific DNA methylation in peripheral blood cells. The aim of this study
      was to investigate in patients with alcohol dependence, who show chronically
      elevated homocysteine levels, whether DNA methylation pattern within the HERP
      (homocysteine-induced endoplasmic reticulum protein) promoter region and
      expression of HERP mRNA is altered. METHODS: The HERP mRNA expression level was
      measured by quantitative PCR in the blood of 66 male alcoholic patients and 55
      nondrinking healthy controls. Epigenetic genomic DNA methylation status and HERP
      promoter methylation were measured with a nonradioactive elongation assay.
      RESULTS: We observed a significant increase (7.6%) in the HERP promoter DNA
      methylation in patients with alcohol dependence (t test, t = -2.45, p < 0.02)
      when compared with healthy controls (80.4%, SD 14.5), which was significantly
      associated with their elevated homocysteine levels (multiple linear regression, p
      < 0.007). Furthermore, we found a significantly lower HERP mRNA expression in
      patients with alcohol dependence (t test, -7.61 DeltaCT; SD 1.87, p < 0.001) when
      compared with healthy controls (-6.04 DeltaCT; SD 2.41). The lowered HERP mRNA
      expression in alcoholic patients was best explained by the hypermethylation of
      the regulatory HERP gene promoter (regression analysis, p = 0.004). CONCLUSIONS:
      To our knowledge, this is the first study evaluating HERP mRNA expression and its
      specific gene promoter methylation in alcoholic patients. As hypermethylation of
      DNA is an important epigenetic factor in the down-regulation of gene expression,
      and as HERP has been considered to play an essential role within the
      intracellular defense system, these findings may be useful in the understanding
      and treatment of different disease conditions associated with alcohol dependence.

PMID- 16573576
TI  - Endogenous kappa opioid receptor systems modulate the responsiveness of
      mesoaccumbal dopamine neurons to ethanol.
AB  - BACKGROUND: Endogenous kappa-opioid receptor (KOPR) systems modulate the actions
      of several drugs of abuse. Their role in modulating the effects of ethanol is
      unknown. An increase in nucleus accumbens extracellular dopamine (DA) has been
      implicated in mediating the rewarding and locomotor-activating effects of ethanol
      and virtually all drugs of abuse. The present microdialysis studies were
      conducted to determine whether the lack of KOPR alters ethanol-evoked DA levels
      in the nucleus accumbens of naive mice and whether a similar effect is observed
      in mice repeatedly exposed to ethanol. METHODS: Gene deletion techniques were
      used in conjunction with in vivo microdialysis to examine the influence of lack
      of KOPR on ethanol-evoked DA in the nucleus accumbens. To determine whether
      pharmacological inactivation of KOPR produces similar effects in naive mice and
      those repeatedly exposed to ethanol, the KOPR antagonist norbinaltorphimine (n
      BNI) was administered in wild-type mice before repeated air or ethanol vapor
      inhalation. Microdialysis was conducted 24 hours later. RESULTS: Acute ethanol
      administration increased DA levels in the nucleus accumbens of wild-type mice. In
      littermates lacking the KOPR gene, ethanol-evoked DA levels were enhanced. Prior
      ethanol exposure reduced ethanol-evoked DA levels in vehicle-treated and n-BNI
      treated mice. Statistical analysis, however, revealed a significant main effect
      of n-BNI, indicating that KOPR blockade increased ethanol-evoked DA levels in
      naive mice and repeated ethanol exposure attenuated, but did not abolish, this
      effect. CONCLUSIONS: These findings demonstrate that inhibition of KOPR leads to
      increased sensitivity to the DA-releasing effects of ethanol in the nucleus
      accumbens.

PMID- 16573577
TI  - Effects of energy drink ingestion on alcohol intoxication.
AB  - BACKGROUND: Well-known reports suggest that the use of energy drinks might reduce
      the intensity of the depressant effects of alcohol. However, there is little
      scientific evidence to support this hypothesis. OBJECTIVE AND METHODS: The
      present study aimed at evaluating the effects of the simultaneous ingestion of an
      alcohol (vodka(37.5%v/v)) and an energy drink (Red Bull-3.57 mL/kg), compared
      with those presented after the ingestion of an alcohol or an energy drink alone.
      Twenty-six young healthy volunteers were randomly assigned to 2 groups that
      received 0.6 or 1.0 g/kg alcohol, respectively. They all completed 3 experimental
      sessions in random order, 7 days apart: alcohol alone, energy drink alone, or
      alcohol plus energy drink. We evaluated the volunteers' breath alcohol
      concentration, subjective sensations of intoxication, objective effects on their
      motor coordination, and visual reaction time. RESULTS: When compared with the
      ingestion of alcohol alone, the ingestion of alcohol plus energy drink
      significantly reduced subjects' perception of headache, weakness, dry mouth, and
      impairment of motor coordination. However, the ingestion of the energy drink did
      not significantly reduce the deficits caused by alcohol on objective motor
      coordination and visual reaction time. The ingestion of the energy drink did not
      alter the breath alcohol concentration in either group. CONCLUSIONS: Even though
      the subjective perceptions of some symptoms of alcohol intoxication were less
      intense after the combined ingestion of the alcohol plus energy drink, these
      effects were not detected in objective measures of motor coordination and visual
      reaction time, as well as on the breath alcohol concentration.

PMID- 16573578
TI  - Comparison of ethanol preference and neurochemical measures of mesolimbic
      dopamine and adenosine systems across different strains of mice.
AB  - BACKGROUND: To extend the known phenotype of strains commonly used in the
      development of mutant mice, ethanol, saccharin, and caffeine preferences were
      examined in C57Bl/6J, CD-1, and hybrid C57Bl/6J x CD-1 mice. As dopaminergic
      mechanisms are inherently involved in the neuronal processing of many drugs of
      abuse (including ethanol), and an important role for adenosine-dopamine
      interactions has also been reported, the dopaminergic and purinergic
      neurochemical profiles of mice were compared against the consummatory phenotype
      observed. METHODS: Ethanol (5% v/v), saccharin (0.1% w/v), and caffeine (0.1%
      w/v) consumption and preference were examined using a 2-bottle free-choice
      paradigm. Dopamine and adenosine receptor and transporter mRNA and protein
      density were quantified using in situ hybridization histochemistry and in vitro
      autoradiography, respectively. RESULTS: C57Bl/6J and hybrid C57Bl/6J x CD-1 mice
      demonstrated a clear ethanol preference, voluntarily consuming large quantities
      of ethanol when given the choice between drinking vessels containing either
      ethanol or water. Conversely, CD-1 mice were characterized as ethanol-avoiding
      under the present paradigm. Differences in D(1) receptor mRNA between the strains
      were consistent with the observed behavioral differences in ethanol preference.
      The high ethanol-preferring phenotype of C57Bl/6J mice could not be directly
      linked to alterations in dopamine transporter neurochemistry and/or enkephalin
      levels as proposed by earlier researchers. Ethanol-seeking behavior appeared to
      correlate with D2 receptor expression, however, with evidence that ethanol
      preferring mice also exhibit an increased density of D2 receptors within limbic
      dopaminergic projection nuclei. Interestingly, strain differences in the
      expression of the ethanol-sensitive nucleoside transporter paralleled differences
      in ethanol consumption, a novel finding consonant with purinergic involvement in
      dopamine-related behaviors. CONCLUSIONS: This study has highlighted the relevance
      of alterations in dopamine receptor expression and purinergic modulation within
      the mesolimbic pathway and predisposition toward the development of ethanol
      seeking behavior.

PMID- 16573579
TI  - Enhanced morphine-induced ethanol drinking in alcohol-preferring alko alcohol
      rats sensitized to morphine.
AB  - BACKGROUND: Alcohol-preferring alko alcohol (AA) rats are more susceptible to
      morphine-induced behavioral and neurochemical sensitization than alcohol
      nonpreferring alko nonalcohol (ANA) rats. Alko alcohol rats sensitized to
      morphine, however, do not show enhanced acquisition of ethanol drinking. The
      purpose of the present study was to clarify further interactions between morphine
      induced behavioral sensitization and voluntary ethanol drinking in the AA rats.
      METHODS: Alko alcohol rats drinking ethanol in a limited 6-hour access paradigm
      were sensitized to morphine with repeated injections of morphine (5-15 mg/kg).
      Injection days alternated with days of ethanol access. Controls had access only
      to water and/or were given injections of saline. After a 5-day washout period
      from ethanol and morphine, the rats were challenged with morphine or saline and
      subsequent ethanol drinking or locomotor activity was recorded. RESULTS: Ethanol
      intake was suppressed during the repeated treatment with morphine, and the
      morphine-treated rats did not differ in ethanol intake from the controls when
      given access to ethanol after the washout. Intake of ethanol was, however,
      increased when the rats were challenged with morphine [1 or 10 mg/kg,
      subcutaneously (s.c.)], while in the controls an increase in ethanol intake was
      seen only after 1 mg/kg morphine. Sensitization to the locomotor stimulating
      effects of morphine was revealed in the morphine-treated rats after a challenge
      with morphine (3 or 10 mg/kg, s.c.). The controls that had been drinking ethanol
      also showed a sensitized response after morphine (3 mg/kg). CONCLUSIONS: Ethanol
      did not interfere with the development of sensitization to morphine. Furthermore,
      the neuroadaptations induced by repeated exposure to ethanol were sufficient to
      cause behavioral cross-sensitization to morphine. Sensitization to the behavioral
      effects of morphine alone, however, neither enhances the reinforcing properties
      of voluntarily consumed ethanol nor contributes to increase in its intake. The
      increase in ethanol intake found after an acute dose of morphine was augmented in
      rats withdrawn from repeated treatment with morphine. The data suggest that the
      neuronal mechanisms underlying behavioral sensitization to morphine probably are
      distinct from those mediating reinforcement from ethanol and that the morphine
      induced neuroadaptations contribute to the enhancement of increase in ethanol
      intake by morphine.

PMID- 16573580
TI  - A pilot study of oxcarbazepine versus acamprosate in alcohol-dependent patients.
AB  - OBJECTIVES: This pilot study has been designed to collect preliminary data on the
      use of a new antiepileptic drug in the management of alcoholic patients.
      Oxcarbazepine (OXC) blocks voltage-sensitive sodium channels. Its metabolite
      reduces high-voltage-activated calcium currents in striatal and cortical neurons,
      thus reducing glutamatergic transmission at corticostriatal synapses. This
      reduction is of interest in the treatment of alcohol dependence, as acamprosate
      (ACP) modulates NMDA receptors, resulting in an inhibition of glutamatergic
      transmission. Furthermore, OXC has revealed a mood-stabilizing effect in bipolar
      affective disorders. We have compared OXC with ACP in relapse prevention in
      recently withdrawn alcohol-dependent patients. METHODS: We investigated the
      efficacy and safety of OXC (vs ACP) by conducting a 24-week randomized, parallel
      group, open-label, clinical trial on 30 acutely detoxified alcoholic patients.
      Survival analyses (Kaplan-Meier) were performed to look for evidence of a longer
      "survival" of patients receiving OXC. We assessed time to first severe relapse
      and additional secondary endpoints. RESULTS: After withdrawal, time to severe
      relapse and time to first consumption of any ethanol by OXC patients were not
      longer than for ACP patients. Abstinent patients in both study groups showed a
      significantly lower obsessive compulsive drinking scale-German version (OCDS-G)
      than relapsed patients. No undesired effects occurred when OXC patients consumed
      alcohol. CONCLUSION: Our findings indicate that it could be worthwhile to test
      relapse prevention using OXC in an adequate sample. While the current sample size
      clearly limits further conclusions from this pilot study, it is noteworthy that
      OXC is well tolerated, even when alcohol is on board. Thus, in medication-based
      relapse prevention, OXC could be a promising alternative for alcoholic patients
      unable to benefit from ACP or naltrexone or those who have affective liability.
      OXC certainly merits a larger placebo-controlled trial.

PMID- 16573581
TI  - Short-term prognosis of community-acquired bacteremia in patients with liver
      cirrhosis or alcoholism: A population-based cohort study.
AB  - BACKGROUND: Liver cirrhosis is associated with an increased risk of infection and
      a poor prognosis, but the role of alcoholism in these outcomes is uncertain. This
      study looks at the short-term prognosis for bacteremia in patients with alcoholic
      liver cirrhosis, nonalcoholic liver cirrhosis, and alcoholism, compared with the
      prognosis for other bacteremia cases. METHODS: All patients who were hospitalized
      with their first community-acquired bacteremia in North Jutland County, Denmark,
      in the period 1992 to 2002 were retrieved from a population-based bacteremia
      registry. Denmark's Hospital Discharge Registry then allowed us to disaggregate
      these patients into the following groups: 47 patients with alcoholic liver
      cirrhosis, 19 with nonalcoholic liver cirrhosis, 190 with alcoholism, and a
      comparison group of 3,535 other bacteremia cases. Using logistic regression, we
      estimated odds ratios (ORs) for 30-day case fatality for the main study variable,
      adjusted for gender, age, focus of infection, and comorbidity. RESULTS: The case
      fatality rate (CFR) was 43% for patients with alcoholic liver cirrhosis, 32% for
      patients with nonalcoholic liver cirrhosis, 24% for patients with alcoholism, and
      15% for other bacteremia patients. The adjusted OR estimates for patients with
      alcoholic liver cirrhosis, nonalcoholic liver cirrhosis, and alcoholism compared
      with other bacteremia cases were 6.3 (95% CI 3.3-11.7), 2.4 (95% CI 0.9-6.7), and
      2.5 (95% CI 1.7-3.7), respectively. Focus of infection and group of bacteria did
      not noticeably affect the increased CFR. CONCLUSION: Liver cirrhosis and
      alcoholism were associated with a poor short-term prognosis for community
      acquired bacteremia. Liver cirrhosis and alcoholism may have independent effects
      on the prognosis for patients with liver cirrhosis and bacteremia.

PMID- 16573582
TI  - Use of record linkage to examine alcohol use in pregnancy.
AB  - BACKGROUND: To date, no population-level data have been published examining the
      obstetric and neonatal outcomes for women with an alcohol-related hospital
      admission during pregnancy compared with the general obstetric population. This
      information is critical to planning and implementing appropriate services.
      METHODS: Antenatal and delivery admissions to New South Wales (NSW) hospitals
      from the NSW Inpatient Statistics Collection were linked to birth information
      from the NSW Midwives Data Collection over a 5-year period (1998-2002). Birth
      admissions were flagged as positive for maternal alcohol use where a birth
      admission or any pregnancy admission for that birth involved an alcohol-related
      International Statistical Classification of Diseases and Related Health Problems,
      10th Revision, Australian Modification (ICD-10-AM) code. Key demographic,
      obstetric, and neonatal variables were compared for births to mothers in the
      alcohol group with births where no alcohol-related ICD10-AM was recorded.
      RESULTS: A total of 416,834 birth records were analyzed over a 5-year period
      (1998-2002). In this time, 342 of these were coded as positive for at least 1
      alcohol-related ICD-10-AM diagnosis. Mothers in the alcohol group had a higher
      number of previous pregnancies, smoked more heavily, were not privately insured,
      and were more often indigenous. They also presented later on in their pregnancy
      to antenatal services and were more likely to arrive at hospital unbooked for
      delivery. Deliveries involved less epidural and local and more general
      anesthesia. Cesarean sections were more common to women in the alcohol group and
      were performed more often for intrauterine growth retardation. Neonates born to
      women in the alcohol group were smaller for gestational age, had lower Apgar
      scores at 5 minutes, and were admitted to special care nursery more often.
      CONCLUSIONS: This study shows that linked population-level administrative data
      provide a powerful new source of information for examining the maternal and
      neonatal outcomes associated with alcohol use in pregnancy.

PMID- 16573583
TI  - Comorbidity of alcohol abuse and dependence with medical conditions in 2 American
      Indian reservation communities.
AB  - BACKGROUND: The objective was to examine the association of self-reported
      Diagnostic and Statistical Manual-IV edition alcohol abuse and dependence with
      medical conditions among American Indians (AIs). METHODS: We analyzed data
      previously collected in a large epidemiological study of members of 2 culturally
      distinct AI tribes from the Southwest (SW; n = 1,446) and the Northern Plains
      (NP; n = 1,638) living on or near their reservations. Associations of combined
      self-reported alcohol abuse and alcohol dependence with 19 medical conditions
      were examined through multinomial logistic regression. RESULTS: Medical
      conditions that had significant relationships with alcohol abuse/dependence were
      sprains and strains [odds ratio (OR) 2.04, p < 0.001], hearing and vision
      problems (OR 2.05, p < 0.001), kidney and bladder problems (OR 1.55, p < 0.01),
      head injuries (OR 2.20, p < 0.001), pneumonia/tuberculosis (OR 1.49, p < 0.01),
      dental problems (OR 1.89, p < 0.001), and liver problems/pancreatitis (OR 2.18, p
      < 0.001). The total count of medical conditions was also significantly related to
      alcohol abuse/dependence, with a higher count being associated with the outcome
      (OR 1.17, p < 0.001). CONCLUSIONS: In this community-based study of rural AIs,
      diverse medical conditions were associated with alcohol abuse and dependence.
      Further research should examine, and confirm, the nature, extent, and tribal
      variation of the medical consequences of alcohol abuse and dependence in these
      unique populations.

PMID- 16573584
TI  - Alcohol-related social consequences in Castille and Leon, Spain.
AB  - BACKGROUND: The purpose of this study was to examine the prevalence of alcohol
      related social problems, as well as to assess the relationship between alcohol
      related social problems and patterns of alcohol consumption in the general
      population during the year 2004. METHODS: A total of 2,500 individuals, age range
      from 14 to 70 years, in Castille and Leon, Spain, were surveyed in 2004 for their
      patterns of alcohol consumption and alcohol-related social consequences during
      the previous year. RESULTS: Participants who admitted to having had some kind of
      social problem related to the consumption of alcohol in the previous year were
      6.5%, with a mean of 2.4 alcohol-related social problems. The most frequent
      problems cited were "argument, discussion, or serious conflict without physical
      aggression" (3%). CONCLUSIONS: The present study shows that the reporting of
      alcohol-related social problems was quite frequent and that having alcohol
      related social problems was related to drunkenness episodes in the previous year,
      having 5 or more drinks on a single occasion in the previous year, and alcohol
      intake.

PMID- 16573585
TI  - Binge alcohol treatment increases vertebral bone loss following ovariectomy:
      compensation by intermittent parathyroid hormone.
AB  - BACKGROUND: Postmenopausal estrogen deficiency and alcohol abuse are known risk
      factors for osteoporosis. Previous studies of the combined effect of alcohol and
      ovariectomy on bone loss using chronic alcohol-feeding models have not
      demonstrated additional alcohol-induced bone loss in ovariectomized (OVX)
      animals. Binge alcohol treatment causes rapid bone loss in male rats. We
      hypothesized that binge alcohol would cause additional bone loss in OVX rats.
      METHODS: Ninety-six adult (400 g) female Sprague-Dawley rats (48 sham-operated
      and 48 OVX, pair fed) were randomly divided into 4 treatment groups: (a) saline
      treated, (b) binge alcohol-treated (3 g/kg alcohol as a 20% weight to volume
      alcohol/saline solution, intraperitoneal (IP), 3 times per week), (c) parathyroid
      hormone (PTH)-treated (80 microg/kg, SC, 5 d/wk), and (d) binge alcohol plus PTH.
      Rats were treated for either 2 or 4 weeks. Following treatment periods, blood was
      collected for alcohol concentration (BAC) measurements; lumbar vertebrae were
      removed for bone mineral density (BMD) levels, trabecular microarchitecture
      assessment, and vertebral compressive strength analysis. RESULTS: Peak binge BACs
      averaged 300 mg/dL. Alcohol and OVX decreased cancellous BMD: alcohol and OVX
      treatment in combination caused additional cancellous BMD loss and significant
      cortical BMD reductions. Compressive strength was also decreased by OVX and
      alcohol. Combination treatment resulted in further declines in bone strength.
      Micro-CT analysis revealed a significant effect of combined OVX and alcohol
      treatment resulting in decreased trabecular bone volume/total volume (BV/TV).
      Intermittent PTH administration compensated for losses of BMD, compressive
      strength, and restored BV/TV deficits caused by OVX, alcohol, or their
      combination. CONCLUSIONS: Bone loss following OVX can be significantly increased
      by concurrent binge alcohol treatment. The effects of alcohol and OVX are
      compensated by concurrent intermittent treatment with PTH. These results suggest
      that postmenopausal women who abuse alcohol may place their skeleton at
      additional risk for osteoporotic fracture.

PMID- 16573587
TI  - Visuoperceptual learning in alcoholic Korsakoff syndrome.
AB  - Relative to the characteristically profound deficits of explicit memory,
      components of implicit memory remain largely intact in patients with alcohol
      induced Korsakoff syndrome (KS). Perceptual priming occurs in KS and transfer of
      learning has been consistently observed on mirror reading, a perceptual reversal
      task. Although priming also occurs with fragmented pictures, a perceptual closure
      task, it is unclear whether transfer of learning can occur. This study examined
      visuoperceptual learning in 4 men with alcoholic KS, 9 recently detoxified
      alcoholic men (ALC), 21 healthy age-matched normal control men (NC), and 6 young
      normal control men (YNC). Subjects were tested with the Gollin Incomplete
      Pictures Test at initial and 1-hour and 1-day retest sessions. Both alcoholic
      groups (KS, ALC) were impaired in visuoperceptual ability. All subject groups
      showed visuoperceptual learning. The KS group showed additional learning after
      continued exposure to the stimuli, despite their nonmnemonic visuospatial
      deficits and profound explicit memory impairment for the test stimuli. Transfer
      of learning to similar but new stimuli was not evident in either the KS or young
      healthy control subjects; learning occurred only for the specific items
      presented. The persistence of learning beyond the life of the percept, which was
      independent of declarative features (such as item recall), suggests that
      perceptual learning and memory reflects an intact cognitive memory process in KS.
      This process is likely mediated by posterior cortical networks relatively
      unaffected in KS and that are independent of the hippocampal-diencephalic
      declarative memory system.

PMID- 16573586
TI  - Effects of 8 different NR1 splice variants on the ethanol inhibition of
      recombinant NMDA receptors.
AB  - BACKGROUND: N-Methyl-D-aspartate (NMDA) receptors are glutamate-activated ion
      channels that are assembled from NR1 and NR2 subunits. These receptors are highly
      enriched in brain neurons and are considered to be an important target for the
      acute and chronic effects of ethanol. NR2 subunits (A-D) arise from separate
      genes and are expressed in a developmental and brain region-specific manner. The
      NR1 subunit has 8 isoforms that are generated by alternative splicing of a single
      gene. The heteromeric subunit makeup of the NMDA receptor determines the
      pharmacological and biophysical properties of the receptor and provides for
      functional receptor heterogeneity. Although results from previous studies suggest
      that NR2 subunits affect the ethanol sensitivity of NMDA receptors, the role of
      the NR1 subunit and its multiple splice variants is less well known. METHODS: In
      this study, all 8 NR1 splice variants were individually coexpressed with each NR2
      subunit in human embryonic kidney 293 (HEK293) cells and tested for inhibition by
      ethanol using patch-clamp electrophysiology. RESULTS: All 32 subunit combinations
      tested gave reproducible glutamate-activated currents and all receptors were
      inhibited to some degree by 100 mM ethanol. The sensitivity of individual
      receptors to ethanol was affected by the specific NR1 splice variant expressed
      with receptors containing the NR1-3 and NR1-4 subunits among the least inhibited
      by ethanol. CONCLUSIONS: These results suggest that regional, developmental, or
      compensatory changes in the expression of NR1 splice variants may significantly
      affect ethanol inhibition of NMDA receptors.

PMID- 16573588
TI  - Social environmental influences on the development and resolution of alcohol
      problems.
AB  - This article summarizes the proceedings of a symposium presented at the 2005
      Annual Meeting of the Research Society on Alcoholism, Santa Barbara, California,
      June 25-30. The overall goal of the symposium was to consider the broad impact of
      the social environment on the development of and successful or unsuccessful
      resolution of drinking problems. The presentations addressed multiple social
      environmental influences including: the influence of children on parents (Dr.
      Zucker), the influence of peers and parents on adolescents (Dr. Molina), the
      influence of family members on adult drinking (Dr. McCrady), the influence of
      adult peers/friends (Dr. Kaskutas), and the influence of the occupational
      environment (Dr. Ames). Dr. Longabaugh, the symposium discussant, addressed
      models for understanding the relationships between social influences and drinking
      problems.

PMID- 16573590
TI  - Hepatitis C infection and alcohol use: A dangerous mix for the liver and
      antiviral immunity.
AB  - This article presents the proceedings of a symposium presented at the meeting of
      the Research Society on Alcoholism, held in Santa Barbara, California, in June
      2005. The organizers and chairs were Sam Zakhari and Gyongyi Szabo. The
      presentations included (1) Mitochondrial Abnormalities Induced by Hepatitis C 
      Alcohol Interaction by Steven Weinman; (2) Effects of Acute and Chronic Ethanol
      on Innate Antiviral Signaling Pathways, Hepatitis C Replication, and Human Liver
      Cell Transcription by Stephen Polyak; (3) Ethanol Alters Dendritic Cell Function
      In Vivo and Impairs the Subsequent Cellular Immune Responses to Hepatitis C
      Proteins by Costica Aloman; and (4) Pathogenic Interactions Between Hepatitis C
      Virus and Alcohol Use in Humans: Dendritic Cells as Common Targets by Gyongyi
      Szabo. This symposium summarizes the state of knowledge of cellular and molecular
      pathways by which alcohol and HCV have pathogenic interactions resulting in
      depression of the immune response and liver damage in chronic HCV infection.

PMID- 16573589
TI  - DNA microarray and proteomic strategies for understanding alcohol action.
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 was James M. Sikela, and he and Michael F. Miles were
      chairs. The presentations were (1) Genomewide Surveys of Gene Copy Number
      Variation in Human and Mouse: Implications for the Genetics of Alcohol Action, by
      James M. Sikela; (2) Regional Differences in the Regulation of Brain Gene
      Expression: Relevance to the Detection of Genes Associated with Alcohol-Related
      Traits, by Robert Hitzemann; (3) Identification of Ethanol Quantitative Trait
      Loci Candidate Genes by Expression Profiling in Inbred Long Sleep/Inbred Short
      Sleep Congenic Mice, by Robnet T. Kerns; and (4) Quantitative Proteomic Analysis
      of AC7-Modified Mice, by Kathleen J. Grant.

PMID- 16573591
TI  - Cytokines and alcohol.
AB  - Cytokines are multifunctional proteins that play a critical role in cellular
      communication and activation. Cytokines have been classified as being
      proinflammatory (T helper 1, Th1) or anti-inflammatory (T helper 2, Th2)
      depending on their effects on the immune system. However, cytokines impact a
      variety of tissues in a complex manner that regulates inflammation, cell death,
      and cell proliferation and migration as well as healing mechanisms. Ethanol
      (alcohol) is known to alter cytokine levels in a variety of tissues including
      plasma, lung, liver, and brain. Studies on human monocyte responses to pathogens
      reveal ethanol disruption of cytokine production depending upon the pathogen and
      duration of alcohol consumption, with multiple pathogens and chronic ethanol
      promoting inflammatory cytokine production. In lung, cytokine production is
      disrupted by ethanol exacerbating respiratory distress syndrome with greatly
      increased expression of transforming growth factor beta (TGFbeta). Alcoholic
      liver disease involves an inflammatory hepatitis and an exaggerated Th1 response
      with increases in tumor necrosis factor alpha (TNFalpha). Recent studies suggest
      that the transition from Th1 to Th2 cytokines contribute to hepatic fibrosis and
      cirrhosis. Cytokines affect the brain and likely contribute to changes in the
      central nervous system that contribute to long-term changes in behavior and
      neurodegeneration. Together these studies suggest that ethanol disruption of
      cytokines and inflammation contribute in multiple ways to a diversity of
      alcoholic pathologies.

PMID- 16573593
TI  - Surveillance stool cultures: to collect or not collect, that is the question.

PMID- 16573594
TI  - Adipocyte signaling: at the crossroads of metabolism, inflammation, and vascular
      function.

PMID- 16573595
TI  - Living donor intestinal transplantation--should it be used more frequently?

PMID- 16573596
TI  - Immunotherapy with virus-specific cytotoxic T lymphocytes after organ
      transplantation.
AB  - Adoptive immunotherapy with antigen specific cytotoxic T lymphocytes can
      favorably impact the outcome of serious herpesvirus infections in organ
      transplant recipients. Current challenges in this field include the determination
      of which patients are at highest risk, and the development of protocols that
      permit more rapid expansion of virus specific effector cells.

PMID- 16573592
TI  - Basis of the gabamimetic profile of ethanol.
AB  - This article summarizes the proceedings of a symposium held at the 2005 Research
      Society on Alcoholism meeting. The initial presentation by Dr. Wallner provided
      evidence that selected GABA(A) receptors containing the delta subunit display
      sensitivity to low intoxicating ethanol concentrations and this sensitivity is
      further increased by a mutation in the cerebellar alpha6 subunit, found in
      alcohol-hypersensitive rats. Dr. Mameli reported that ethanol affects gamma
      aminobutyric acid (GABA) function by affecting neural circuits that influence
      GABA release. Dr. Parsons presented data from electrophysiological and
      microdialysis investigations that ethanol is capable of releasing GABA from
      presynaptic terminals. Dr. Morrow demonstrated that systemic ethanol increases
      neuroactive steroids in brain, the absence of which alters various functional
      responses to ethanol. Dr. Criswell presented evidence that the ability of ethanol
      to increase GABA was apparent in some, but not all, brain regions indicative of
      regional specificity. Further, Dr. Criswell demonstrated that neurosteroids alone
      and when synthesized locally by ethanol act postsynaptically to enhance the
      effect of GABA released by ethanol in a region specific manner. Collectively,
      this series of reports support the GABAmimetic profile of acutely administered
      ethanol being dependent on several specific mechanisms distinct from a direct
      effect on the major synaptic isoforms of GABA(A) receptors.

PMID- 16573597
TI  - Hyperbaric oxygen therapy: a useful adjunct therapy in pediatric hepatic arterial
      thrombosis.

PMID- 16573598
TI  - Anti-HLA alloantibodies in pediatric solid organ transplantation.
AB  - An increasing number of studies demonstrate the clinical impact of preformed and
      de novo anti-human leucocyte antigen alloantibody (HLA-Ab) in solid organ
      transplantation (Tx). The screening of HLA-Ab in candidates and transplant
      recipients has evolved over time, with continuous improvement in the sensitivity
      and specificity of assays for HLA-Ab detection. Furthermore, histologic markers
      of complement activation pathways are currently implemented in the diagnosis of
      antibody-mediated rejection (AMR). Therapeutic strategies, including depletion of
      HLA-Ab and B cells, have allowed Tx across antibody barriers, or have rescued
      patients with AMR. The purpose of the present review is to summarize the state-of
      the-art of HLA-Ab detection, clinical significance and therapeutic strategies in
      pediatric solid organ Tx.

PMID- 16573599
TI  - Liver transplantation in children with Alagille syndrome: indications and
      outcome.
AB  - An AGS is a dominant inherited multisystem disorder caused by mutations in the
      Notch signaling pathway (JAG1). In our center, 5.3% of liver transplantations
      (OLT) are performed in children with AGS. Some of the affected children fulfilled
      criteria for OLT, despite the absence of liver cirrhosis. The aim of our present
      study was to evaluate the indications and outcome for OLT in children with this
      complex disorder as clear criteria are difficult to establish in clinical
      practice. A total of 37 patients were included in a retrospective analysis.
      Twenty-four children underwent OLT for chronic end-stage liver failure (n = 8) or
      symptomatic liver disease (n = 16). Patient survival post-OLT was 91.7% after 1
      yr, that of graft survival was 87.5%, respectively. Significant post-transplant
      vascular complications included a mid-aortic syndrome (n = 1) and severe lethal
      bleeding due to suspected vascular malformation (n = 1). Severe
      hypercholesterolemia (>800 mg/dL) and xanthomata resolved completely in affected
      patients. We conclude from our data that indications for OLT in AGS should be
      extended to patients with severe symptomatic liver disease, even in the absence
      of liver cirrhosis because of the significantly improved outcome after pediatric
      OLT in the last decade. Future studies must identify underlying mechanisms of
      hypercholesterolemia and vascular malformation.

PMID- 16573600
TI  - Outpatient pediatric renal transplant biopsy--is it safe?
AB  - The safe observation time following pediatric renal transplant biopsy is unknown.
      To predict the safety of day-care pediatric renal transplant biopsy, we
      retrospectively evaluated the timing, incidence and severity of post-biopsy
      complications in children observed overnight. Biopsies were performed under real
      time ultrasound guidance using an 18-gauge Bard Biopty needle. Coagulation screen
      and platelet counts were measured preprocedure. Hemoglobin (Hb) was measured
      preprocedure, at 6 h and at 1-day post-procedure. Twenty-eight of 45 children
      transplanted between January 2002 and May 2004 underwent 65 biopsies. There was
      gross hematuria following 8 (12%) biopsies; 2/8 occurred after 6 h. Hb fell by
      >15 g/L in six cases (9%) - three had Hb drop within 6 h post-procedure and three
      had a steady decline over 24 h. No patient required blood transfusion. Oral
      analgesia post-procedure was required in seven cases (11%). One of these had
      gross hematuria. No patient required surgical intervention or transfusion. Three
      complications were recorded >6 h post-biopsy but none required intervention.
      Daycare renal transplant biopsy appears to be safe in selected patients.

PMID- 16573601
TI  - Gastrointestinal tract ulcers in pediatric intestinal transplantation patients:
      etiology and management.
AB  - One of the observed complications in patients after intestinal transplantation is
      the occurrence of ulcers in the native or transplanted gastrointestinal tract.
      Previous reports have described the appearance of ulcers but have not described
      any systemic approach to accurately diagnose the etiology of the ulcer. We
      evaluated 112 intestinal transplantation patients at our institution, in which
      endoscopic examination identified ulcer formation in 11 patients. No common or
      defining demographic or clinical variables were found in the patients with
      ulcers. Biopsies were obtained from the ulcer edge as well as the intervening
      mucosa. The most common changes in the ulcers were compatible with post
      transplant lymphoproliferative disorder (PTLD), acute rejection, and viral
      infections. These changes could occur simultaneously and retrospective analysis
      showed that ulcers could have concomitant etiologies. Endoscopically directed
      biopsies of ulcer edges often displayed morphologic changes compatible with acute
      rejection of the graft. Some patients were treated for rejection based on the
      changes within the mucosa outside the ulcer bed, and they responded with
      resolution of the ulcers. Our findings demonstrate that PTLD and acute rejection
      are the most common causes of chronic ulcer formation and reinforce the concept
      that biopsy samples should be collected simultaneously from both the ulcer edge
      and intervening mucosa.

PMID- 16573602
TI  - Cyclosporine drug monitoring with C0 and C2 concentrations in children with
      stable renal allograft function.
AB  - Cyclosporin A (CsA) has a narrow therapeutic window and necessitates monitoring
      of blood concentration. We aimed to evaluate trough (C0) and second hour (C2)
      level after ingestion of drug monitoring in renal allograft recipients. In this
      retrospective study, 12 children eight boys and four girls; mean age at
      transplantation 14.6 +/- 3.7 yr (ranges: 7.0-19.0), mean age post-transplant 17.8
      +/- 4.9 yr (ranges: 9.0-24.0) who were transplanted >6 months were enrolled in
      this evaluation. Ten were recipients of a living related donor and two deceased
      donor grafts. While six children were receiving CsA, steroids and azathioprine,
      the other six received CsA, steroids and mycophenolate mofetil. Clinical course,
      blood pressure, renal and liver function tests were recorded. Mean C0 and C2 were
      96.2 +/- 59.5 and 504 +/- 305.4 ng/mL respectively. Mean serum creatinine level
      was 1.2 +/- 0.45 mg/dL and mean creatinine clearance (CrCl) was 89.2 +/- 36.8
      mL/min/1.73 m2. There was a correlation between serum creatinine level, CsA dose
      and C2 levels,whereas,there was no correlation between age, blood pressure, CrCl
      and C2 levels. However, no correlation was found between C0 levels and any of the
      above parameters. In conclusion, our data suggest that C2 levels are correlated
      better with dose and serum creatinine level.

PMID- 16573603
TI  - Improved pain management in pediatric postoperative liver transplant patients
      using parental education and non-pharmacologic interventions.
AB  - A pain management intervention, consisting of pretransplant parental education
      and support, pre- and postoperative behavioral pediatrics consultation,
      postoperative physical and occupational therapy consultation, and implementation
      of non-pharmacologic pain management strategies, was introduced to all pediatrics
      patients receiving liver transplants at Lucile Packard Children's Hospital
      beginning August 2001. Children receiving transplants pre-intervention (May, 2000
      to February, 2001) and post-intervention (August, 2001 to March, 2002) were
      compared using pain scores, parent perception of pain ratings, length of stay,
      ventilator days, total cost, and opioid use. A total of 27 children were
      evaluated (13 historical control, 14 intervention). The two populations did not
      differ on age at transplant (mean age 53.8 vs. 63.6 months), sex (46.1% vs. 50%
      male), ethnicity (53.8% vs. 57.1% white, non-Hispanic) weight at transplant (17.5
      vs. 24.7 kg), percent with biliary atresia as the primary reason for transplant
      (42.9% vs. 69.2%), percent with status 1 transplant listing score (38.5% vs.
      50.0%), or public insurance status (30.8 vs. 57.2% with Medicaid). No differences
      were found in mean pediatric intensive care unit (PICU) postoperative length of
      stay (6.7 vs. 5.3 days), total postoperative length of stay (17.5 vs. 17.5 days),
      total inpatient length of stay (27.0 vs. 24.4 days), time to extubation (30 vs.
      24.3 h), total cost (dollar 147,983 vs. dollar 157,882) or opioid use through
      postoperative day (POD) 6 (0.24 vs. 0.25 mg/kg/day morphine equivalent). A
      decrease in mean pain score between POD 0 and 6 (2.82 vs. 2.12; p = 0.047), a
      decrease in mean parental pain perception score (3.1 vs. 2.1; p = 0.001), and an
      increase in number of pain assessments per 12 h shift (3.43 vs. 6.79; p < 0.005)
      were seen. A comprehensive non-pharmacologic postoperative pain management
      program in children receiving a liver transplant was associated with decreased
      pain scores, improved parent perception of pain, and an increased number of pain
      assessments per 12 h shift. No increases in lengths of stay (PICU, postoperative,
      total), time to extubation, or total cost were found.

PMID- 16573604
TI  - Peripheral blood mononuclear cell responses to heat shock proteins in patients
      undergoing stem cell transplantation.
AB  - GVHD is a major complication after allogeneic SCT. Etiology of GVHD is
      multifactorial. Known role of hSPS in antigen presentation could suggest their
      potential role in the alloreactive process that leads to aGVHD. HSPS represent
      major immunodominant antigens in a wide spectrum of microbial pathogens.
      Bacterial and fungal colonization, infection and sepsis are frequent in
      immunocompromised patients with various malignant and non-malignant diseases. We
      studied PBMC responses to recombinant human hsp60 (rh-hsp60), rh-hsp70 and
      Mycobacterium bovis hsp65 (M. bovis hsp65) in relation to aGVHD and infection in
      34 pediatric patients with various lympho-hemopoietic malignancies as well as non
      malignant disorders subjected to SCT. PBMC of patients before initiation of
      preparative regimen as well as after engraftment were stimulated with hSPS (1
      microg/mL/well, 7-day cultivation). PHA was used as a control of the stimulation
      ability. Cell responses were measured after the incorporation of 3H-thymidin
      (pulsing with 1 microCi/well) and were expressed as stimulation indexes (SI). We
      demonstrated significantly high proliferative response to rh-hsp60 as well as M.
      bovis hsp65 in a cohort of pretransplant patients with anamnestic and/or actual
      infection when compared with a cohort of patients without infection and healthy
      individuals. Strong PBMC cell responses to hSPS were found in patients who were
      at present colonized with Escherichia coli and Klebsiella pneumoniae or had
      previously K. pneumoniae infection with subsequent sepsis. Our findings support
      various studies dealing with immunodominant hSPS in connection with several
      pathogens and infectious diseases. Although no statistical difference for
      proliferative response to PHA was observed, PBMC responses against all tested
      hSPS comparing a cohort of patients with aGVHD and that with no sign of GVHD
      resulted in significantly lower SI for all tested hSPS in patients with aGVHD.
      Lower stimulation with hSPS during aGVHD might be explained by the stress-induced
      upregulation of self-hSPS synthesis that might lead to the inhibition of self
      hSPS reactive T-cell response. Vice versa, we hypothesize that increased hsp
      specific stimulation may reflect the presence of protecting regulatory T cells
      preventing the development of Th1-mediated diseases involving aGVHD.

PMID- 16573605
TI  - Adiponectin levels and arteriosclerotic risk factors in pediatric renal
      transplant recipients.
AB  - ADPN, a recently discovered adipocytokine, has attracted great attention because
      of its anti-atherogenic properties. It was suggested as a protective factor for
      the cardiovascular system because of its close correlation with several risk
      factors. Our aim was to investigate serum ADPN levels in pediatric RTR and to
      document possible relationships between ADPN and arteriosclerotic risk factors.
      Twenty-one RTR, aged 16.3 +/- 4.0 yr, and 23 healthy age and sex-matched control
      subjects were enrolled in this study. Serum lipid/lipoprotein fractions,
      homocysteine and ADPN levels as well as intima-media thickness of the cIMT were
      determined in both groups. Significantly higher serum ADPN (p < 0.001) and
      homocysteine (p < 0.05) levels as well as higher cIMT (p < 0.001) were found in
      RTR compared with the control subjects, whereas apolipoprotein B and lipoprotein
      (a) levels were not significantly different. HDL cholesterol was positively
      correlated with log ADPN (r = 0.585, p < 0.01). There were inverse correlations
      between log time post-transplantation and log ADPN as well as HDL cholesterol (r
      = -0.438, p < 0.05 and r = -0.578, p < 0.05, respectively). There were no
      correlation between log ADPN, log homocysteine, log apolipoprotein B, lipoprotein
      (a), creatinine clearance and cumulative steroid dose. Despite reasonable lipid
      profiles and remarkably elevated ADPN levels, our pediatric RTR with stable graft
      function displayed a risk for arteriosclerosis because of increased cIMT and mild
      hyperhomocysteinemia. Regarding the close positive correlation between ADPN and
      HDL cholesterol, it could be speculated that ADPN is a novel negative surrogate
      marker of arteriosclerosis. To our knowledge, this is the only report
      investigating levels and diverse correlates of ADPN in a pediatric RTR group.
      Further studies in larger groups of recipients are needed to clarify the
      interaction between arteriosclerotic risk factors and ADPN.

PMID- 16573606
TI  - Pediatric renal transplantation: a single center experience over 14 years.
AB  - Between 1989 and 2003, 100 transplants were performed in 96 patients at the
      pediatric nephrology unit of the Calvo Mackenna Children's Hospital. Mean age
      10.9 +/- 3.9 yr (1-17.6), 30% from LD. Donors were younger than 5 yr in five
      patients and all recipients received an 'en bloc' graft. Original disease was
      hypo/dysplasia 27%, reflux nephropathy 22 and 17% chronic glomerulonephritis. The
      immunosuppressive protocol during the first period (n = 56, 1989-2000):
      Cyclosporine, steroids and azathioprine, and during the second period (n = 44,
      2001-2003): FK, steroids, MMF and anti-CD25 antibody (mAbs). AR was reported in
      22 patients, 11% in LD, 31% in DD (p < 0.01). The AR rate decreased from 40 to 8%
      after anti-CD25 monoclonal induction. Patient actuarial survival rate at 1, 3 and
      5 yr was 100% for LD and 96% for DD. The overall actuarial graft survival at 1,3,
      and 5 yr was 96.7, 96.7 and 71% for LD and 89, 76 and 73% for DD donors. Graft
      survival rate improved from the first period (1989-2000) to the second period
      (2001-2003; p = 0.05). No difference in graft survival rate with HLA-A,B,DR
      matching was found. Graft survival rate was better when cold ischemia time was
      <24 h (p < 0.01). CMV infections increased from 19 to 40% when MMF and anti-CD25
      Ab were introduced (p < 0.01). The height/age Z score at 1, 3 and 5 yr post
      transplant was -2.2, -2.1, -2.2, respectively, for children older than 7 yr and 
      1.8, -1.9, -2.1 for those transplanted younger than 7 yr of age who were switched
      to alternate day steroids (p < 0.01). The cause of graft lost was: chronic
      rejection eight, non-adherence four, AR four and vascular thrombosis two. The
      cause of death in two patients was fungus septicemia and accelerated rejection.
      Pediatric renal transplantation can be performed in our group with acceptable
      morbidity, low mortality and graft survival rates similar to other reports in
      North America and Western Europe. Graft survival rate improved with newer
      immunosuppression and greater experience at the center. Management of non
      adherence and chronic rejection remain the major challenges.

PMID- 16573607
TI  - Impact of surveillance stool culture guided selection of antibiotics in the
      management of pediatric small bowel transplant recipients.
AB  - Surveillance stool cultures (SSC) have been used in immunocompromised populations
      to predict the organisms associated with invasive infections and aid in the
      selection of empiric antibiotic regimens. To evaluate the utility of this
      approach in pediatric small bowel transplant (SBT) recipients, we conducted a
      retrospective review of 33 patients who underwent SBT, 16 of whom had SSC done.
      In no case was the same organism isolated from SSC and subsequent blood,
      peritoneal fluid or wound cultures. In the first month post-transplantation,
      blood cultures were positive in 44% and 35% of patients that had and did not have
      SSC done, respectively (p = 0.73); peritoneal fluid cultures in 44% and 65% (p =
      0.30); and wound cultures in 44% and 24% (p = 0.28). There were no significant
      differences among both groups in time to first infection, duration of ICU stay
      following SBT, graft survival or long-term patient survival. We conclude that SSC
      guided antibiotic selection does not have a significant impact on the incidence
      of invasive infections in the first month following SBT or on specific indicators
      of patient outcome. This suggests that empiric antibiotic regimens should be
      selected based on clinical presentation and hospital flora and susceptibility
      patterns.

PMID- 16573608
TI  - Emotional and behavioral problems after pediatric liver transplantation: a
      quantitative assessment.
AB  - Several uncertainties regarding psychological problems in children who underwent
      liver transplantation and the need to differentiate these disturbances from those
      related to the underlying previous chronic liver disease itself exist. This
      background triggered the present pilot study to investigate, using quantitative
      assessment methods, the incidence and the type of emotional and behavioral
      disturbances after liver transplantation. Sixteen liver transplant recipients
      (aged 5.7-14.4 yr) and 12 age-matched controls with stable chronic liver disease
      were assessed through the parent report form of Child Behavior Checklist/ 4-18.
      The mean time elapsed since transplantation was 8.1 yr. No patient or family had
      received psychological support during chronic liver disease or at any phase of
      the transplantation process. Transplanted children scored within borderline range
      for Internalizing and Total Behavioral Problems and within pathological range for
      Competences, except for the Activity Scale. Transplanted children showed more
      Total Behavioral (p = 0.005) and Externalizing Problems (p = 0.0005) than
      controls. Both groups scored within the pathological range for Total Competences
      with no significant differences between the two groups. Our findings suggest that
      in the absence of support programs a psychological risk does exist for a long
      period of time, after transplantation. Regarding Total Behavioral Problems and
      Externalizing Problems, this risk is higher than in children with chronic liver
      disease.

PMID- 16573609
TI  - Skin changes in pediatric transplant patients.
AB  - The advent of organ transplantation identified a new group of diseases.
      Dermatologists are studying transplant-associated diseases along with the
      atypical behavior of already known dermatoses. Pediatric patients have been
      treated as an extension of adult population, but unique aspects of age required
      clarification. A prospective cohort was studied including patients from both
      genders up to 17 yr of age who were recipients of kidney, liver or BMT during
      2003 in Porto Alegre, Brazil. Regular skin examinations were performed up to the
      sixth month after the procedure, and an analysis was determined by ID (i.e. =
      number of skin changes/number of patients-month x 100). Thirty-nine patients were
      examined: 20 were kidney transplant recipients; 11 were BMT recipients (10
      autologous transplants and 1 allogeneic transplant); and 8 were liver transplant
      recipients. Skin changes result primarily from the use of medication (87.2).
      Individually, kidney transplant patients presented the highest ID of skin changes
      because of medications (104.1). BMT recipients presented the highest ID of
      alterations occurring on skin appendages (85.4) and liver transplant recipients
      had the highest ID of vascular changes (94.9). In conclusion, this study shows
      that cutaneous alterations in pediatric transplant recipients present some
      particularities not described in adult recipients, such as ichthyosiform xerosis
      in renal recipients and skin scaling with pellagroid appearance in bone marrow
      recipients. Also, dermatoses secondary to medication use were the main finding in
      pediatric population.

PMID- 16573610
TI  - Concomitant oral findings in children after cardiac transplant.
AB  - Heart transplantations have been performed in the Centre for Paediatric Heart
      Surgery at the Justus Liebig University in Giessen (Germany) since 1988. For
      further consultation and therapy, some affected children subsequently present at
      the Polyclinic for Paediatric Dentistry. In all these cases problematic oral
      findings were diagnosed. It was the aim of this study to describe the different
      findings and to create a concept for avoiding them in the future. Altogether, 10
      children with cardiac transplants (three girls, seven boys) were examined and,
      where necessary, treated. At the time they first presented, they were between 23
      and 119 months old (average = 72.2) and had all been operated on (organ
      transplant) in the first 6 months of life. Each child showed evidence of gingival
      hyperplasia in the area of the front teeth, which was because of ongoing
      immunosuppression. In three patients, reactive mucosal caps avoided the age
      related penetration of a permanent incisor in the upper jaw. In addition, the
      primary teeth of six children were affected by caries; in two of these cases, the
      damage was because of the nursing-bottle syndrome. The results show that any
      infant with cardiac transplant has to be subjected to careful dental examination
      and offered comprehensive medical care in cooperation with the competent centre
      for child cardiac surgery. Furthermore, the parents of such children should be
      informed prior to transplantation about the possibility of subsequent findings
      and how these findings can be either avoided or, if necessary, adequately
      treated.

PMID- 16573611
TI  - Tacrolimus-induced cholestatic syndrome following pediatric liver transplantation
      and steroid-resistant graft rejection.
AB  - Several factors may contribute to post-transplant cholestatic complications after
      liver transplantation. These include ischemic reperfusion injury, hypoperfusion,
      bile duct strictures, and hepatotoxic drugs. Up to now, there have been no
      publications on tacrolimus cholestatic toxicity in clinical transplantation when
      the drug was used in therapeutic doses. We describe six pediatric liver graft
      recipients in whom cholestatic complications developed under a tacrolimus-based
      immunosuppression following liver transplantation and all of them suffered from
      previous steroid-resistant graft rejection. The overall incidence of cholestatic
      syndrome was 5.4% in children receiving tacrolimus. The immunosuppression was
      switched back to cyclosporine and prednisolone in all six patients resulting in
      completely resolved clinical signs and laboratory findings. We conclude from our
      observations that a cholestatic syndrome following pediatric liver
      transplantation may be caused by tacrolimus therapy following steroid-resistant
      graft rejection, even if given in therapeutic doses.

PMID- 16573612
TI  - Idiopathic infantile arterial calcification: two case reports, a review of the
      literature and a role for cardiac transplantation.
AB  - Idiopathic infantile arterial calcification (IIAC) is a rare, but important,
      cause of rapidly progressive ischemic heart disease in children. In this paper,
      we report two recent cases of IIAC seen at tertiary referral hospitals. Both
      cases presented in infancy with signs of heart failure and, ultimately, died with
      the diagnosis of IIAC confirmed at postmortem examination. A thorough review of
      the literature reveals approximately 160 reported cases of IIAC. The clinical
      outcomes, radiographic findings and pathologic details are summarized. Proposed
      etiologic mechanisms are reviewed, including promising research into the role of
      inorganic pyrophosphate as a regulatory factor in the development of IIAC.
      Because of the typically fatal outcome of IIAC and the lack of proven therapies,
      the potential role for cardiac transplantation is discussed.

PMID- 16573613
TI  - Hyperbaric oxygen therapy for hepatic artery thrombosis following liver
      transplantation: current concepts.
AB  - This article presents the case of an infant who underwent an orthotopic liver
      transplant and then developed hepatic artery thrombosis that was detected on
      routine post-operative right upper quadrant ultrasound. Alteplase (TPA) failed to
      open the artery, so the child received systemic heparin and hyperbaric oxygen
      (HBO) therapy. After six HBO treatments, the hepatic artery had recanalized and
      his liver function tests had returned to normal or near normal. There were no
      complications to the HBO therapy, and 1 yr after the transplant, the child's
      liver is functioning well. The present study discusses the beneficial effects of
      HBO therapy and the proposed mechanisms for its favorable results. In our
      patient, systemic heparin and HBO therapy prevented liver failure and need for
      retransplantation.

PMID- 16573614
TI  - Specific autologous cytotoxic T lymphocytes for chronic varicella in a liver
      transplanted child.
AB  - Infections by herpesviruses may have severe complications in liver transplant
      patients. Although prophylactic varicella zoster virus vaccination is strongly
      recommended and widely applied, severe infection may still occur. We report the
      case of systemic chronic varicella, which developed in a liver allograft
      recipient, unresponsive to antiviral drug treatment, successfully treated by
      varicella zooster-specific CTL. Graft failure ensued, likely, because of massive
      cytolysis of infected hepatocytes. The patient, who was re-transplanted in the
      absence of signs of varicella zooster reactivation, is now well and disease free
      3 yr after second liver transplant.

PMID- 16573615
TI  - Living-related intestinal transplantation for a patient with hypoganglionosis.
AB  - A 14-yr-old boy with total parenteral nutrition-dependent short-bowel syndrome
      associated with hypoganglionosis underwent the LR-IT by using a 150 cm segment of
      distal ileum taken from a healthy donor. The graft vessels were connected to
      infrarenal aorta and inferior vena cava. The immunosuppressive regimen consisted
      of daclizumab, tacrolimus, and steroid. The graft surveillance for ACR was
      accomplished using zoom endoscopy and mucosal biopsy. The blood trough level of
      tacrolimus was maintained between 20 and 25 ng/mL for the first 2 months,
      followed by 15-20 ng/mL thereafter. The 50 mg of daclizumab was administered on
      the day of operation, and same dosage was repeated at 2-wk intervals. The first
      ACR occurred on POD-9 and was progressive, and required a 14-day course of OKT-3
      injection. After the treatment with OKT-3, the graft recovered from the ACR, and
      began to function well enough to discontinue the intravenous nutrition on POD-55.
      No infectious complication has occurred. The patient was discharged in POD-112,
      and currently tolerates full oral intake without requiring intravenous
      nutritional or fluid supplementation. The donor was discharged without any
      complications. The LR-IT could successfully be performed with minimal risk to the
      donor, and it can be a treatment of choice for patients with short-gut syndrome
      associated with hypoganglionosis.

PMID- 16573616
TI  - Feasibility of duct-to-duct biliary reconstruction in pediatric living related
      liver transplantation: report of three cases.
AB  - Feasibility of duct-to-duct biliary reconstruction in adult living related liver
      transplantation (LRLTx) has been recently reported; however, little has been
      known of its surgical outcome in children. To assess the feasibility and safety
      of duct-to-duct biliary reconstruction in children, the surgical outcomes of duct
      to-duct biliary reconstruction were retrospectively analyzed. The subjects were
      three children who underwent LRLTx in our hospital each utilizing allografts with
      a right lobe, a left robe and a lateral segment, respectively. The cause of end
      stage liver disease in each of them was fulminant Wilson's disease, fulminant
      hepatic failure and unresectable hepatoblastoma. Duct-to-duct anastomosis was
      performed in younger patients and adolescents with interrupted and continuous
      sutures, respectively. The diameter of bile duct in allografts was from 4 to 6 mm
      and 12 or 13 stitches were required for anastomosis. Post-operative
      choledochography from the external tube showed neither stenosis nor leakage and
      the tube was evacuated within 3 months after LRLTx. No biliary complications were
      observed with the median follow-up of 28 months. In conclusion, our results show
      that duct-to-duct biliary reconstructions in pediatric LRLTx seemed to be
      feasible and safe. Further studies are required to elucidate its real impact on
      pediatric LRLTx.

PMID- 16573617
TI  - Capsule endoscopy as a diagnostic tool in the evaluation of graft-vs.-host
      disease.
AB  - Capsule endoscopy is a relatively new technology that has allowed
      gastroenterologists to visualize the mucosa of the small intestine. This
      technology is playing an expanding role in both adult and pediatric
      gastroenterology. In this report, we present an 8-yr-old child following
      allogeneic hematopoietic cell transplantation who developed large volume bloody
      diarrhea requiring multiple packed red blood cell transfusions that was resistant
      to aggressive therapy for GVHD. The capsule endoscopy performed on this patient
      provided significant information not provided by upper endoscopy and colonoscopy
      that allowed for successful treatment changes. This case demonstrates that
      capsule endoscopy is a diagnostic tool that may play an important role in the
      assessment of patients, including children, with possible GVHD.

PMID- 16573618
TI  - Assessment of nephrotoxicity of high-cumulative dose of liposomal amphotericin B
      in a pediatric patient who underwent allogeneic bone marrow transplantation.
AB  - We describe a 9-yr-old boy who received the highest cumulative dose so far
      reported of liposomal amphotericin B. The patient underwent an allogeneic bone
      marrow transplantation (BMT) for adrenoleucodystrophy, after a conditioning
      regimen with busulfan, thiothepa and cyclophosphamide. Rabbit antithymoglobulin,
      cyclosporin and prednisone were used as prophylaxis against graft vs. host
      disease (GVHD). Post-transplant Epstein-Bar-virus-related lymphoma was diagnosed
      on day +68 and was treated with donor-derived lymphocytes. The patient developed
      a severe form of GVHD, and a progressive worsening of his neurological status
      because of progression of his underlying disease. Death from septic shock
      occurred 23 months after BMT. During prolonged hospitalization, 19,750 mg of
      liposomal amphotericin B, about 1000 mg/kg, were given for prophylactic or
      empirical therapeutic purposes without significant nephrotoxicity. This case
      suggests that liposomal amphotericin B is safe and well-tolerated even if is
      administered for long periods and a cumulative dose fivefold greater than the
      nephrotoxic threshold of amphotericin B deoxycholate is achieved.

PMID- 16573619
TI  - Fulminant liver failure secondary to mushroom poisoning in children: importance
      of early referral to a liver transplantation unit.
AB  - Patients poisoned with toxic mushrooms have a spectrum of clinical presentations
      ranging from gastrointestinal symptoms to fulminant liver failure, and outcomes
      range from complete recovery to the need for liver transplantation. We reviewed
      the clinical presentation, course, outcome and management of four children
      poisoned with mushrooms who developed fulminant liver failure. Although one
      patient survived, two children died and one underwent living related liver
      transplantation. Early referral to specialized centers for treatment and for
      liver transplantation is emphasized.

PMID- 16573621
TI  - On the definition of vulnerabilities in measuring risks to infrastructures.

PMID- 16573622
TI  - A cost-benefit analysis of alternative device configurations for aviation-checked
      baggage security screening.
AB  - The terrorist attacks of September 11, 2001 have resulted in dramatic changes in
      aviation security. As of early 2003, an estimated 1,100 explosive detection
      systems (EDS) and 6,000 explosive trace detection machines (ETD) have been
      deployed to ensure 100% checked baggage screening at all commercial airports
      throughout the United States. The prohibitive costs associated with deploying and
      operating such devices is a serious issue for the Transportation Security
      Administration. This article evaluates the cost effectiveness of the explosive
      detection technologies currently deployed to screen checked baggage as well as
      new technologies that could be used in the future. Both single-device and two
      device systems are considered. In particular, the expected annual direct cost of
      using these devices for 100% checked baggage screening under various scenarios is
      obtained and the tradeoffs between using single- and two-device strategies are
      studied. The expected number of successful threats under the different checked
      baggage screening scenarios with 100% checked baggage screening is also obtained.
      Lastly, a risk-based screening strategy proposed in the literature is analyzed.
      The results reported suggest that for the existing security setup, with current
      device costs and probability parameters, single-device systems are less costly
      and have fewer expected number of successful threats than two-device systems due
      to the way the second device affects the alarm or clear decision. The risk-based
      approach is found to have the potential to significantly improve security. The
      cost model introduced provides an effective tool for the execution of cost
      benefit analyses of alternative device configurations for aviation-checked
      baggage security screening.

PMID- 16573620
TI  - Option of pre-emptive nephrectomy and renal transplantation for Bartter's
      syndrome.
AB  - Bartter's syndrome (BS) is an incurable genetic disease, with variable response
      to supportive therapy relating to fluid and electrolyte management. Poor control
      or therapy non-compliance may result in frequent life threatening episodes of
      dehydration, acidosis and hypokalemia, with resultant adverse effects on patient
      quality of life (QOL). We report, for the first time, pre-emptive bilateral
      native nephrectomies and successful renal transplantation, prior to the onset of
      ESRD, for severe, clinically brittle, neonatal BS, resulting in correction of
      metabolic abnormalities and excellent graft function. We propose that fragile BS
      should be considered as a possible indication for early native nephrectomies and
      pre-emptive renal transplantation, procedures that results in a 'cure' for the
      underlying disease and significant improvements in patient QOL.

PMID- 16573623
TI  - Reliability analysis based on the losses from failures.
AB  - The conventional reliability analysis is based on the premise that increasing the
      reliability of a system will decrease the losses from failures. On the basis of
      counterexamples, it is demonstrated that this is valid only if all failures are
      associated with the same losses. In case of failures associated with different
      losses, a system with larger reliability is not necessarily characterized by
      smaller losses from failures. Consequently, a theoretical framework and models
      are proposed for a reliability analysis, linking reliability and the losses from
      failures. Equations related to the distributions of the potential losses from
      failure have been derived. It is argued that the classical risk equation only
      estimates the average value of the potential losses from failure and does not
      provide insight into the variability associated with the potential losses.
      Equations have also been derived for determining the potential and the expected
      losses from failures for nonrepairable and repairable systems with components
      arranged in series, with arbitrary life distributions. The equations are also
      valid for systems/components with multiple mutually exclusive failure modes. The
      expected losses given failure is a linear combination of the expected losses from
      failure associated with the separate failure modes scaled by the conditional
      probabilities with which the failure modes initiate failure. On this basis, an
      efficient method for simplifying complex reliability block diagrams has been
      developed. Branches of components arranged in series whose failures are mutually
      exclusive can be reduced to single components with equivalent hazard rate,
      downtime, and expected costs associated with intervention and repair. A model for
      estimating the expected losses from early-life failures has also been developed.
      For a specified time interval, the expected losses from early-life failures are a
      sum of the products of the expected number of failures in the specified time
      intervals covering the early-life failures region and the expected losses given
      failure characterizing the corresponding time intervals. For complex systems
      whose components are not logically arranged in series, discrete simulation
      algorithms and software have been created for determining the losses from
      failures in terms of expected lost production time, cost of intervention, and
      cost of replacement. Different system topologies are assessed to determine the
      effect of modifications of the system topology on the expected losses from
      failures. It is argued that the reliability allocation in a production system
      should be done to maximize the profit/value associated with the system.
      Consequently, a method for setting reliability requirements and reliability
      allocation maximizing the profit by minimizing the total cost has been developed.
      Reliability allocation that maximizes the profit in case of a system consisting
      of blocks arranged in series is achieved by determining for each block
      individually the reliabilities of the components in the block that minimize the
      sum of the capital, operation costs, and the expected losses from failures. A
      Monte Carlo simulation based net present value (NPV) cash-flow model has also
      been proposed, which has significant advantages to cash-flow models based on the
      expected value of the losses from failures per time interval. Unlike these
      models, the proposed model has the capability to reveal the variation of the NPV
      due to different number of failures occurring during a specified time interval
      (e.g., during one year). The model also permits tracking the impact of the
      distribution pattern of failure occurrences and the time dependence of the losses
      from failures.

PMID- 16573624
TI  - Why people believe they were exposed to biological or chemical warfare: a survey
      of Gulf War veterans.
AB  - The study sought to understand better how people come to believe they have been
      exposed to biological and chemical warfare. We conducted telephone interviews
      with 1,009 American veterans (65% response rate) deployed and not deployed to the
      Gulf War, a conflict during which there were credible threats that such warfare
      could be used. Only 6% of non-Gulf War veterans reported exposure to biological
      or chemical warfare, but most of Gulf War veterans reported exposure (64%). The
      majority of these were unsure whether the exposure was chemical or biological in
      nature. The most commonly reported exposure indicators were receiving an alert
      from the military and having physical symptoms. Veterans who were certain of the
      type of exposure (biological or chemical) were more likely to recall having been
      told by the military and to recall physical symptoms. Future communications with
      soldiers and the general public about biological and chemical warfare may need to
      emphasize the uncertain nature of such risk information. Evaluations of exposure
      diagnostic technologies should take into account the problem of people initially
      believing, but not later discounting, false positive results.

PMID- 16573625
TI  - Out of the frying pan into the fire: behavioral reactions to terrorist attacks.
AB  - A low-probability, high-damage event in which many people are killed at one point
      of time is called a dread risk. Dread risks can cause direct damage and, in
      addition, indirect damage mediated though the minds of citizens. I analyze the
      behavioral reactions of Americans to the terrorist attacks on September 11, 2001,
      and provide evidence for the dread hypothesis: (i) Americans reduced their air
      travel after the attack; (ii) for a period of one year following the attacks,
      interstate highway travel increased, suggesting that a proportion of those who
      did not fly instead drove to their destination; and (iii) for the same period, in
      each month the number of fatal highway crashes exceeded the base line of the
      previous years. An estimated 1,500 Americans died on the road in the attempt to
      avoid the fate of the passengers who were killed in the four fatal flights.

PMID- 16573626
TI  - Applying a health behavior theory to explore the influence of information and
      experience on arsenic risk representations, policy beliefs, and protective
      behavior.
AB  - The common sense model (CSM) shows how people process information to construct
      representations, or mental models, that guide responses to health threats. We
      applied the CSM to understand how people responded to information about arsenic
      contaminated well water. Constructs included external information (arsenic level
      and information use), experience (perceived water quality and arsenic-related
      health effects), representations, safety judgments, opinions about policies to
      mitigate environmental arsenic, and protective behavior. Of 649 surveys mailed to
      private well users with arsenic levels exceeding the maximum contaminant level,
      545 (84%) were analyzed. Structural equation modeling quantified CSM
      relationships. Both external information and experience had substantial effects
      on behavior. Participants who identified a water problem were more likely to
      reduce exposure to arsenic. However, about 60% perceived good water quality and
      60% safe water. Participants with higher arsenic levels selected higher personal
      safety thresholds and 20% reported a lower arsenic level than indicated by their
      well test. These beliefs would support judgments of safe water. A variety of
      psychological and contextual factors may explain judgments of safe water when
      information suggested otherwise. Information use had an indirect effect on policy
      beliefs through understanding environmental causes of arsenic. People need
      concrete information about environmental risk at both personal and environmental
      systems levels to promote a comprehensive understanding and response. The CSM
      explained responses to arsenic information and may have application to other
      environmental risks.

PMID- 16573628
TI  - Insurability and mitigation of flood losses in private households in Germany.
AB  - In Germany, flood insurance is provided by private insurers as a supplement to
      building or contents insurance. This article presents the results of a survey of
      insurance companies with regard to eligibility conditions for flood insurance
      changes after August 2002, when a severe flood caused 1.8 billion euro of insured
      losses in the Elbe and the Danube catchment areas, and the general role of
      insurance in flood risk management in Germany. Besides insurance coverage,
      governmental funding and public donations played an important role in loss
      compensation after the August 2002 flood. Therefore, this article also analyzes
      flood loss compensation, risk awareness, and mitigation in insured and uninsured
      private households. Insured households received loss compensation earlier. They
      also showed slightly better risk awareness and mitigation strategies. Appropriate
      incentives should be combined with flood insurance in order to strengthen future
      private flood loss mitigation. However, there is some evidence that the surveyed
      insurance companies do little to encourage precautionary measures. To overcome
      this problem, flood hazards and mitigation strategies should be better
      communicated to both insurance companies and property owners.

PMID- 16573627
TI  - Risk migration and scientific advance: the case of flame-retardant compounds.
AB  - It is a common experience that attempts to mitigate a risk lead to new risks, and
      that risks formerly thought to be of one kind become another kind as technical
      knowledge evolves. This phenomenon of risk migration suggests that we should take
      processes over time, rather than specific risks or specific technologies, as a
      unit of analysis. Several of our existing models of the social management of
      risks-such as that of social risk amplification-are process models of a kind but
      are still oriented around the playing out of a particular event or issue. A case
      study of risk in a group of flame-retardant compounds was used as the basis of a
      grounded, exploratory analysis of migration processes, the phenomena that
      influence them, and their consequences. This illustrated how migration naturally
      occurs from risks that are understood, in which risk bearers have at least some
      agency, to risks that are not understood and not capable of being influenced by
      risk bearers. It illustrated how the simultaneous improvement in measuring
      technology, which detects potential toxins at increasingly small concentrations,
      combines with intuitive models that ignore concentration to produce conditions
      likely to generate anxiety. And it illustrated how pressure groups and commercial
      interests exploit this effect. It also showed how migration makes precautionary
      action problematic, and how more generally it tends to undermine a society's
      capacity to cope with risk.

PMID- 16573629
TI  - Current directions in risk research: new developments in psychology and
      sociology.
AB  - This article reviews the main approaches to risk in psychology and sociology and
      considers recent developments. It shows that research continues from a wide range
      of perspectives. Some developments in psychological thinking have recently
      acknowledged the importance of the cultural framing of risk perceptions and
      responses and the positive power of emotions to manage uncertainties, while some
      streams of work in sociology have moved toward more individualist approaches.
      These converging processes open opportunities for cross-fertilization and for
      using insights from both disciplines in the development of research.

PMID- 16573631
TI  - Why do neighbors have different environmental priorities? Analysis of
      environmental risk perception in a Beirut neighborhood.
AB  - Differences in environmental priorities within an urban neighborhood of Beirut
      are analyzed. The explanatory capabilities of five categories of contextual
      variables are compared: socioeconomic status, locality, health, behavior, and
      environmental beliefs. Semi-structured interviews with key individuals in the
      community and residents were first conducted. Four environmental issues of
      concern were identified. A survey was carried out to identify the relative
      priority accorded by respondents to these four issues, and to measure variables
      likely to explain differences of opinion. Bivariate and multivariate logistic
      regression analyses were conducted for each of the four problems. The 99%
      confidence interval (CI) of the odds ratio (OR) was used as a test of
      significance. Respondents suffering from a respiratory disease (OR = 6.94, 99%CI
      = 1.54-31.25), those living in less crowded houses (OR = 4.88, 99%CI = 1.38
      17.24), and those not living close to the neighborhood's industrial street
      (OR=5.26, 99%CI = 1.01-27.78) are significantly more likely to rank poor air
      quality first. Significant associations are found between poor water quality as
      first priority and nonpresence of a smoker in the household (OR = 6.12, 99%CI =
      1.84-20.32) and perception of water salinity as a problem (OR = 7.46, 99%CI =
      1.50-37.03). Males (OR = 6.94, 99%CI = 1.02-47.62) and tenants versus owners (OR
      = 10.49, 99%CI = 1.36-80.61) are significantly more likely to rank the
      residential-industrial mix first. Socioeconomic variables retain their
      explanatory capability in the studied neighborhood, despite relatively small
      income disparities. Behavioral variables, such as smoking, may be causative
      factors of priorities. Analyzing relative priorities, rather than "concern" or
      lack of it, reveals more complex patterns of association. Identifying
      environmental-perception divide lines can help develop a more inclusive and
      effective participatory environmental management.

PMID- 16573630
TI  - Discovering spatio-temporal models of the spread of West Nile virus.
AB  - Emerging infectious diseases are characterized by complex interactions among
      disease agents, vectors, wildlife, humans, and the environment. Since the
      appearance of West Nile virus (WNV) in New York City in 1999, it has infected
      over 8,000 people in the United States, resulting in several hundred deaths in 46
      contiguous states. The virus is transmitted by mosquitoes and maintained in
      various bird reservoir hosts. Its unexpected introduction, high morbidity, and
      rapid spread have left public health agencies facing severe time constraints in a
      theory-poor environment, dependent largely on observational data collected by
      independent survey efforts and much uncertainty. Current knowledge may be
      expressed as a priori constraints on models learned from data. Accordingly, we
      applied a Bayesian probabilistic relational approach to generate spatially and
      temporally linked models from heterogeneous data sources. Using data collected
      from multiple independent sources in Maryland, we discovered the integrated
      context in which infected birds are plausible indicators for positive mosquito
      pools and human cases for 2001 and 2002.

PMID- 16573632
TI  - Place, culture, and the social amplification of risk.
AB  - This article investigates the role of culture in the social production of risks
      and risk communication surrounding industrial development in a region located at
      a rural-urban interface. A case study examined a public consultation that was
      undertaken to inform local residents about an eco-industrial development proposal
      being planned near Edmonton, Alberta, Canada. The research employed the social
      amplification of risk framework (SARF) to examine the relationships among
      culture, place, and socially constructed risk. A total of 44 in-depth, semi
      structured interviews were carried out with 33 landowners (farmers, acreage
      owners), public officials (municipal politicians, administrators), journalists,
      and industry representatives. Analysis revealed that risk communication occurred
      in relation to situated experiences of place that were based on conflicting
      cultural worldviews. The research shows that place is a useful component of the
      SARF, providing a spatial explanation for why some people amplify, and others
      attenuate, risks in locally contentious environmental debates.

PMID- 16573633
TI  - Loss of agro-biodiversity, uncertainty, and perceived control: a comparative risk
      perception study in Austria and China.
AB  - The biogeographical centers of origin of important food crops-called Vavilov
      centers-are considered to be crucial sources of genetic diversity for present and
      future crop-breeding programs and thus for human food safety worldwide. Global
      environmental change and more intensified modes of crop production may cause
      genetic erosion (loss of traditional crop varieties and loss of crop wild
      relatives), especially in Vavilov centers. The present study focused on how the
      risk of genetic erosion (or loss of agro-biodiversity) is perceived in comparison
      to 16 other risk topics by experts and lay people in Austria and China. The most
      striking result was that genetic erosion was perceived to be an exceptionally
      unknown and uncertain risk topic, given that only genetically modified organisms
      (GMOs) were perceived as being even more uncertain. As a consequence of the high
      uncertainty, the idea of applying the precautionary principle to further prevent
      genetic erosion is discussed. An unprecedented finding-one that differs from
      Austrian participants-is that the Chinese have a higher perceived control over
      all risk topics. The increased perception of controllability in China is
      discussed in light of the theory of reflexive modernization. This theory strives
      to explain the increased critical attitude in Western countries such as Austria
      toward scientific innovations and toward the idea that everything can be
      calculated and mastered at will. By revealing different notions of risk
      perception, this research also provides additional scientific input to risk
      communication efforts for public education.

PMID- 16573634
TI  - Leukemia attributable to residential magnetic fields: results from analyses
      allowing for study biases.
AB  - Nearly every epidemiologic study of residential magnetic fields and childhood
      leukemia has exhibited a positive association. Nonetheless, because these studies
      suffer from various methodologic limitations and there is no known plausible
      mechanism of action, it remains uncertain as to how much, if any, of these
      associations are causal. Furthermore, because the observed associations are small
      and involve only the highest and most infrequent levels of exposure, it is
      believed that the public health impact of an effect would be small. We present
      some formal analyses of the impact of power-frequency residential magnetic-field
      exposure (as measured by attributable fractions), accounting for our
      uncertainties about study biases as well as uncertainties about exposure
      distribution. These analyses support the idea that the public health impact of
      residential fields is likely to be limited, but both no impact and a substantial
      impact remain possibilities in light of the available data.

PMID- 16573635
TI  - Physiologically-based pharmacokinetic modeling of genistein in rats, Part I:
      Model development.
AB  - Genistein is a phytoestrogen-a plant-derived compound that binds to and activates
      the estrogen receptor-occurring at high levels in soy beans and food products,
      leading to widespread human exposure. The numerous scientific publications
      available describing genistein's dosimetry, mechanisms of action, and identified
      or putative health effects in both experimental animals and humans make it ideal
      for examination as an example of endocrine-active compound (EAC). We developed a
      physiologically-based pharmacokinetic (PBPK) model to quantify the internal,
      target-tissue dosimetry of genistein in adult rats. Complexities of the model
      include enterohepatic circulation, binding of both genistein and its conjugates
      to plasma proteins, and the multiple compartments used to describe transport
      through the bile duct and gastrointestinal tract. Other aspects of the model are
      simple perfusion-limited transport to the tissue groups and first-order rates of
      metabolism, uptake, and excretion. We describe here the model structure and
      initial calibration of the model by fitting to a large data set for Wistar rats.
      The model structure can be readily extrapolated to describe genistein dosimetry
      in humans or modified to describe the dosimetry of other phytoestrogens and
      phenolic EACs. The model does a fair job of capturing the pharmacokinetics.
      Although it does not describe the interindividual variability and we have not
      identified a single set of parameters that provide a good fit to the data for
      both oral and intravenous exposures, we believe it provides a good initial
      attempt at PBPK modeling for genistein, which can serve as a template for other
      phytoestrogens and in the design of future experiments and research that can be
      used to fill data gaps and better estimate model parameters.

PMID- 16573636
TI  - An integrated physical dispersion and behavioral response model for risk
      assessment of radiological dispersion device (RDD) events.
AB  - A radiological dispersion device (RDD) or "dirty" bomb is a conventional
      explosive wrapped in radiological material. Terrorists may use an RDD to disperse
      radioactive material across a populated area, causing casualties and/or economic
      damage. Nearly all risk assessment models for RDDs make unrealistic assumptions
      about public behavior in their health assessments, including assumptions that the
      public would stand outside in a single location indefinitely. In this article, we
      describe an approach for assessing the risks of RDD events incorporating both
      physical dispersion and behavioral response variables. The general approach is
      tested using the City of Pittsburgh, Pennsylvania as a case study. Atmospheric
      models simulate an RDD attack and its likely fallout, while radiation exposure
      models assess fatal cancer risk. We model different geographical distributions of
      the population based on time of day. We evaluate aggregate health impacts for
      different public responses (i.e., sheltering-in-place, evacuating). We find that
      current RDD models in use can be improved with the integration of behavioral
      components. Using the results from the model, we show how risk varies across
      several behavioral and physical variables. We show that the best policy to
      recommend to the public depends on many different variables, such as the amount
      of trauma at ground zero, the capability of emergency responders to get trauma
      victims to local hospitals quickly and efficiently, how quickly evacuations can
      take place in the city, and the amount of shielding available for shelterers.
      Using a parametric analysis, we develop behaviorally realistic risk assessments,
      we identify variables that can affect an optimal risk reduction policy, and we
      find that decision making can be improved by evaluating the tradeoff between
      trauma and cancer fatalities for various RDD scenarios before they occur.

PMID- 16573637
TI  - A probabilistic arsenic exposure assessment for children who contact CCA-treated
      playsets and decks, Part 1: Model methodology, variability results, and model
      evaluation.
AB  - Concerns have been raised regarding the safety of young children who may contact
      arsenic residues while playing on and around chromated copper arsenate (CCA)
      treated wood playsets and decks. Although CCA registrants voluntarily canceled
      the production of treated wood for residential use in 2003, the potential for
      exposure from existing structures and surrounding soil still poses concerns. The
      EPA's Office of Research and Development developed and applied the probabilistic
      Stochastic Human Exposure and Dose Simulation model for wood preservatives (SHEDS
      Wood) to estimate children's absorbed dose of arsenic from CCA. Skin contact
      with, and nondietary ingestion of, arsenic in soil and wood residues were
      considered for the population of children in the United States who frequently
      contact CCA-treated wood playsets and decks. Model analyses were conducted to
      assess the range in population estimates and the impact of potential mitigation
      strategies such as the use of sealants and hand washing after play events. The
      results show predicted central values for lifetime annual average daily dose
      values for arsenic ranging from 10(-6) to 10(-5) mg/kg/day, with predicted 95th
      percentiles on the order of 10(-5) mg/kg/day. There were several orders of
      magnitude between lower and upper percentiles. Residue ingestion via hand-to
      mouth contact was determined to be the most significant exposure route for most
      scenarios. Results of several alternative scenarios were similar to baseline
      results, except for the scenario with greatly reduced residue concentrations
      through hypothetical wood sealant applications; in this scenario, exposures were
      lower, and the soil ingestion route dominated. SHEDS-Wood estimates are typically
      consistent with, or within the range of, other CCA exposure models.

PMID- 16573638
TI  - A probabilistic arsenic exposure assessment for children who contact chromated
      copper arsenate (CCA)-treated playsets and decks, Part 2: Sensitivity and
      uncertainty analyses.
AB  - A probabilistic model (SHEDS-Wood) was developed to examine children's exposure
      and dose to chromated copper arsenate (CCA)-treated wood, as described in Part 1
      of this two-part article. This Part 2 article discusses sensitivity and
      uncertainty analyses conducted to assess the key model inputs and areas of needed
      research for children's exposure to CCA-treated playsets and decks. The following
      types of analyses were conducted: (1) sensitivity analyses using a percentile
      scaling approach and multiple stepwise regression; and (2) uncertainty analyses
      using the bootstrap and two-stage Monte Carlo techniques. The five most important
      variables, based on both sensitivity and uncertainty analyses, were: wood surface
      residue-to-skin transfer efficiency; wood surface residue levels; fraction of
      hand surface area mouthed per mouthing event; average fraction of nonresidential
      outdoor time a child plays on/around CCA-treated public playsets; and frequency
      of hand washing. In general, there was a factor of 8 for the 5th and 95th
      percentiles and a factor of 4 for the 50th percentile in the uncertainty of
      predicted population dose estimates due to parameter uncertainty. Data were
      available for most of the key model inputs identified with sensitivity and
      uncertainty analyses; however, there were few or no data for some key inputs. To
      evaluate and improve the accuracy of model results, future measurement studies
      should obtain longitudinal time-activity diary information on children, spatial
      and temporal measurements of residue and soil concentrations on or near CCA
      treated playsets and decks, and key exposure factors. Future studies should also
      address other sources of uncertainty in addition to parameter uncertainty, such
      as scenario and model uncertainty.

PMID- 16573639
TI  - Predictive Bayesian microbial dose-response assessment based on suggested self
      organization in primary illness response: Cryptosporidium parvum.
AB  - The probability of illness caused by very low doses of pathogens cannot generally
      be tested due to the numbers of subjects that would be needed, though such
      assessments of illness dose response are needed to evaluate drinking water
      standards. A predictive Bayesian dose-response assessment method was proposed
      previously to assess the unconditional probability of illness from available
      information and avoid the inconsistencies of confidence-based approaches.
      However, the method uses knowledge of the conditional dose-response form, and
      this form is not well established for the illness endpoint. A conditional
      parametric dose-response function for gastroenteric illness is proposed here
      based on simple numerical models of self-organized host-pathogen systems and
      probabilistic arguments. In the models, illnesses terminate when the host evolves
      by processes of natural selection to a self-organized critical value of wellness.
      A generalized beta-Poisson illness dose-response form emerges for the population
      as a whole. Use of this form is demonstrated in a predictive Bayesian dose
      response assessment for cryptosporidiosis. Results suggest that a maximum
      allowable dose of 5.0 x 10(-7) oocysts/exposure (e.g., 2.5 x 10(-7) oocysts/L
      water) would correspond with the original goals of the U.S. Environmental
      Protection Agency Surface Water Treatment Rule, considering only primary
      illnesses resulting from Poisson-distributed pathogen counts. This estimate
      should be revised to account for non-Poisson distributions of Cryptosporidium
      parvum in drinking water and total response, considering secondary illness
      propagation in the population.

PMID- 16573640
TI  - Variability in physical constant parameter values from standard data sources and
      the implication of this variability for risk analysis.
AB  - Physical property values are used in environmental risk assessments to estimate
      media and risk-based concentrations. However, considerable variability has
      recently been reported with such values. To evaluate potential variability in
      physical parameter values supporting a variety of regulatory programs, eight data
      sources were chosen for evaluation, and chemicals appearing in at least four
      sources were selected. There were 755 chemicals chosen. In addition, chemicals in
      seven environmentally important subgroups were also identified for evaluation.
      Nine parameters were selected for analysis-molecular weight (MolWt), melting
      point (MeltPt), boiling point (BoilPt), vapor pressure (VP), water solubility
      (AqSOL), Henry's law constant (HLC), octanol-water partition coefficient (Kow),
      and diffusion coefficients in air (Dair) and water (Dwater). Results show that
      while 71% of constituents had equal MolWts across data sources, <3% of the
      constituents had equivalent parameter values across data sources for AqSOL, VP,
      or HLC. Considerable dissimilarity between certain sources was also observed.
      Furthermore, measures of dispersion showed considerable variation in data sets
      for Kow, VP, AqSOL, and HLC compared to measures for MolWt, MeltPt, BoilPt, or
      Dwater. The magnitude of the observed variability was also noteworthy. For
      example, the 95th percentile ratio of maximum/minimum parameter values ranged
      from 1.0 for MolWt to well over 1.0E + 06 for VP, and HLC. Risk and exposure
      metrics also varied by similar magnitudes. Results with environmentally important
      subgroups were similar. These results show that there is considerable variability
      in physical parameter values from standard sources, and that the observed
      variability could affect potential risk estimates and perhaps risk management
      decisions.

PMID- 16573641
TI  - Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to
      limited flux across the blood-brain barrier constitute a biochemical risk factor
      for neurodegeneration in glutaryl-CoA dehydrogenase deficiency.
AB  - Glutaric acid (GA) and 3-hydroxyglutaric acids (3-OH-GA) are key metabolites in
      glutaryl co-enzyme A dehydrogenase (GCDH) deficiency and are both considered to
      be potential neurotoxins. As cerebral concentrations of GA and 3-OH-GA have not
      yet been studied systematically, we investigated the tissue-specific distribution
      of these organic acids and glutarylcarnitine in brain, liver, skeletal and heart
      muscle of Gcdh-deficient mice as well as in hepatic Gcdh-/- mice and in C57Bl/6
      mice following intraperitoneal loading. Furthermore, we determined the flux of GA
      and 3-OH-GA across the blood-brain barrier (BBB) using porcine brain microvessel
      endothelial cells. Concentrations of GA, 3-OH-GA and glutarylcarnitine were
      significantly elevated in all tissues of Gcdh-/- mice. Strikingly, cerebral
      concentrations of GA and 3-OH-GA were unexpectedly high, reaching similar
      concentrations as those found in liver. In contrast, cerebral concentrations of
      these organic acids remained low in hepatic Gcdh-/- mice and after
      intraperitoneal injection of GA and 3-OH-GA. These results suggest limited flux
      of GA and 3-OH-GA across the BBB, which was supported in cultured porcine brain
      capillary endothelial cells. In conclusion, we propose that an intracerebral de
      novo synthesis and subsequent trapping of GA and 3-OH-GA should be considered as
      a biochemical risk factor for neurodegeneration in GCDH deficiency.

PMID- 16573642
TI  - Graded response to GABA by native extrasynaptic GABA receptors.
AB  - GABA is the main inhibitory neurotransmitter in the mammalian CNS. GABA in the
      brain is commonly associated with a fast, point-to-point form of signalling
      called synaptic transmission (phasic inhibition), but there is growing evidence
      that GABA participates in another, slower and more diffuse form of signalling
      often referred to as tonic inhibition. Unresolved questions regarding tonic
      neuronal inhibition concern activation and functional properties of extrasynaptic
      GABAA receptors (GABARex) present on neurones. Extrasynaptic receptors are
      exposed to submicromolar GABA concentrations and may modulate the overall
      excitability of neurones and neuronal networks. Here, we examined GABA-activated
      single-channel currents in dentate gyrus granule neurones in rat hippocampal
      slices. We activated three types (I, II, III) of GABARex channels by nanomolar
      GABA concentrations (EC50 I: 27 +/- 12; II: 4 +/- 3; III: 43 +/- 19 nm). The
      channels opened after a delay and the single-channel conductance was graded
      (gammamax I: 61 +/- 3; II: 85 +/- 8, III: 40 +/- 3 pS). The channels were
      differentially modulated by 1 microm diazepam, 200 nm zolpidem, 1 microm
      flumazenil and 50 nm THDOC (3alpha, 21-dihydroxy-5alpha-pregnan-20-one),
      consistent with the following minimal subunit composition of GABARex I
      alpha1betagamma2, GABARex II alpha4betagamma2 and GABARex III alphabetadelta
      channels.

PMID- 16573644
TI  - Blood 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and melatonin levels in
      patients with either Huntington's disease or chronic brain injury.
AB  - Following a study of oxidative tryptophan metabolism to kynurenines, we have now
      analysed the blood of patients with either Huntington's disease or traumatic
      brain injury for levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid
      (5-HIAA) and melatonin. There were no differences in the baseline levels of these
      compounds between patients and healthy controls. Tryptophan depletion did not
      reduce 5-HT levels in either the controls or in the patients with Huntington's
      disease, but it increased 5-HT levels in patients with brain injury and lowered 5
      HIAA in the control and Huntington's disease groups. An oral tryptophan load did
      not modify 5-HT levels in the patients but increased 5-HT in control subjects.
      The tryptophan load restored 5-HIAA to baseline levels in controls and patients
      with brain injury, but not in those with Huntington's disease, in whom 5-HIAA
      remained significantly depressed. Melatonin levels increased on tryptophan
      loading in all subjects, with levels in patients with brain injury increasing
      significantly more than in controls. Baseline levels of neopterin and lipid
      peroxidation products were higher in patients than in controls. It is concluded
      that both groups of patients exhibit abnormalities in tryptophan metabolism,
      which may be related to increased inflammatory status and oxidative stress.
      Interactions between the kynurenine, 5-HT and melatonin pathways should be
      considered when interpreting changes of tryptophan metabolism.

PMID- 16573645
TI  - Evidence that caspase-1 is a negative regulator of AMPA receptor-mediated long
      term potentiation at hippocampal synapses.
AB  - Best known for their pivotal role in a form of programmed cell death called
      apoptosis, caspases may also function in more subtle physiological processes.
      Caspases are present in synapses and dendrites of neurons where they can be
      activated in response to glutamate receptor stimulation and calcium influx. Here
      we tested the hypothesis that caspase-1 plays a role in modulating long-term
      potentiation (LTP) at hippocampal synapses. We provide evidence that caspase-1
      plays a role in regulating alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) receptor-mediated calcium influx and synaptic plasticity in the
      hippocampus. LTP of excitatory postsynaptic potentials at CA1 synapses was
      significantly enhanced when hippocampal slices were treated with either a pan
      caspase inhibitor or a selective inhibitor of caspase-1, but not by an inhibitor
      of caspase-6. Inhibition of caspase-1 significantly enhanced the AMPA current
      mediated component of LTP without affecting the N-methyl-D-aspartate current
      mediated component. Calcium responses to AMPA were enhanced in hippocampal
      neurons treated with a caspase-1 inhibitor suggesting that caspase-1 normally
      functions to reduce AMPA receptor-mediated calcium influx. These findings suggest
      that, by selectively reducing AMPA currents and calcium influx, caspase-1
      functions as a negative regulator of LTP at hippocampal synapses.

PMID- 16573646
TI  - Puromycin-purified rat brain microvascular endothelial cell cultures exhibit
      improved barrier properties in response to glucocorticoid induction.
AB  - In vitro blood-brain barrier (BBB) models using primary rat brain microvessel
      endothelial cells (BMEC) are often hampered by a lack of culture purity and poor
      barrier properties. To address these problems, the translation inhibitor
      puromycin was used to purify rat BMEC cultures. BMEC purities of 99.8% were
      routinely attained using puromycin treatment, and this technique proved to be far
      superior to other purification methods of similar difficulty. In contrast to
      cultures without puromycin treatment, purity of puromycin-treated cultures was
      unaffected by initial seeding density. Next, rat BMEC monolayer transendothelial
      electrical resistance (TEER) was increased by glucocorticoid treatment with
      either corticosterone (CORT) or hydrocortisone (HC), and a corresponding decrease
      in monolayer permeability to small molecules was observed. Importantly, cultures
      treated with both puromycin and glucocorticoid attained significantly higher TEER
      values (CORT 168 +/- 13 Omega x cm2; HC 218 +/- 66 Omega x cm2) than those
      treated by the glucocorticoid alone (CORT 57 +/- 5 Omega x cm2; HC 70 +/- 2 Omega
      x cm2). Glucocorticoid induction resulted in BMEC morphological changes that
      accompanied the increases in TEER, and BMEC tight junctions exhibited improved
      integrity as visualized by the localization of tight junction proteins zonula
      occluden-1, occludin and claudin-5. The combined use of puromycin and
      glucocorticoid therefore provides an in vitro system that is well suited for
      molecular level BBB investigations.

PMID- 16573643
TI  - NFkappaB in neurons? The uncertainty principle in neurobiology.
AB  - Nuclear factor kappaB (NFkappaB) is a dynamically modulated transcription factor
      with an extensive literature pertaining to widespread actions across species,
      cell types and developmental stages. Analysis of NFkappaB in a complex
      environment such as neural tissue suffers from a difficulty in simultaneously
      establishing both activity and location. Much of the available data indicate a
      profound recalcitrance of NFkappaB activation in neurons, as compared with most
      other cell types. Few studies to date have sought to distinguish between the
      various combinatorial dimers of NFkappaB family members. Recent research has
      illuminated the importance of these problems, as well as opportunities to move
      past them to the nuances manifest through variable activation pathways, subunit
      complexity and target sequence preferences.

PMID- 16573647
TI  - Chronic depolarization stimulates norepinephrine transporter expression via
      catecholamines.
AB  - Chronic depolarization increases norepinephrine (NE) uptake and expression of the
      norepinephrine transporter (NET) in sympathetic neurons, but the mechanisms are
      unknown. Depolarization of sympathetic neurons stimulates catecholamine
      synthesis, and several studies suggest that NET can be regulated by
      catecholamines. It is not clear if the depolarization-induced increase in NET is
      because of nerve activity per se, or is secondary to elevated catecholamines. To
      determine if induction of NET mRNA was a result of increased catecholamines, we
      used pharmacological manipulations to (i) inhibit tyrosine hydroxylase activity
      in neurons depolarized with 30 mm KCl, thereby preventing increased
      catecholamines, or (ii) stimulate tyrosine hydroxylase activity in the absence of
      depolarization. Inhibiting the depolarization-induced increase in catecholamines
      prevented the up-regulation of NET mRNA, but did not block the increase in
      tyrosine hydroxylase (TH) mRNA. Furthermore, stimulating catecholamine production
      in the absence of depolarization elevated NE uptake, NET protein, and NET mRNA in
      sympathetic neurons. Similarly, elevating endogenous catecholamines in SK-N
      BE2M17 neuroblastoma cells increased NE uptake and NET expression. These data
      suggest that chronic depolarization of sympathetic neurons induces NET expression
      through increasing catecholamines, and that M17 neuroblastoma cells provide a
      model system in which to investigate catechol regulation of NET expression.

PMID- 16573648
TI  - Differential metabolic adaptation to acute and long-term hypoxia in rat primary
      cortical astrocytes.
AB  - Brain astrocytes provide structural and metabolic support to surrounding cells
      during ischemia. Glucose and oxygen are critical to brain function, and glucose
      uptake and metabolism by astrocytes are essential to their metabolic coupling to
      neurons. To examine astrocyte metabolic response to hypoxia, cell survival and
      metabolic parameters were assessed in rat primary cortical astrocytes cultured
      for 3 weeks in either normoxia or in either 1 day or 3 weeks sustained hypoxia
      (5% O2). Although cell survival and proliferation were not affected by the mildly
      hypoxic environment, substantial differences in glucose consumption and lactate
      release after either acute or prolonged hypoxia suggest that astrocyte metabolism
      may contribute to their adaptation. Hypoxia over a period of 1 day increased
      glucose uptake, lactate release, and glucose transporter 1 (GLUT1) and
      monocarboxylate transporter 1 (MCT1) expression, whereas hypoxia over a period of
      3 weeks resulted in a decrease of all parameters. Furthermore, increased glucose
      uptake at 1 day of hypoxia was not inhibited by cytochalasin B suggesting the
      involvement of additional glucose transporters. We uncovered hypoxia-regulated
      expression of sodium-dependent glucose transporters (SGLT1) in astrocytes
      indicating a novel adaptive strategy involving both SGLT1 and GLUT1 to regulate
      glucose intake in response to hypoxia. Overall, these findings suggest that
      although increased metabolic response is required for the onset of astrocyte
      adaptation to hypoxia, prolonged hypoxia requires a shift to an energy
      conservation mode. These findings may contribute to the understanding of the
      relative tolerance of astrocytes to hypoxia compared with neurons and provide
      novel therapeutic strategies aimed at maintaining brain function in cerebral
      pathologies involving hypoxia.

PMID- 16573649
TI  - The protein tyrosine phosphatase, Shp2, is required for the complete activation
      of the RAS/MAPK pathway by brain-derived neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF) and other neurotrophins induce a unique
      prolonged activation of mitogen-activated protein kinase (MAPK) compared with
      growth factors. Characterization and kinetic and spatial modeling of the
      signaling pathways underlying this prolonged MAPK activation by BDNF will be
      important in understanding the physiological role of BDNF in many complex systems
      in the nervous system. In addition to Shc, fibroblast growth factor receptor
      substrate 2 (FRS2) is required for the BDNF-induced activation of MAPK. BDNF
      induces phosphorylation of FRS2. However, BDNF does not induce phosphorylation of
      FRS2 in cells expressing a deletion mutant of TrkB (TrkBDeltaPTB) missing the
      juxtamembrane NPXY motif. This motif is the binding site for SHC. NPXY is the
      consensus sequence for phosphotyrosine binding (PTB) domains, and notably, FRS2
      and SHC contain PTB domains. This NPXY motif, which contains tyrosine 484 of
      TrkB, is therefore the binding site for both FRS2 and SHC. Moreover, the proline
      containing region (VIENP) of the NPXY motif is also required for FRS2 and SHC
      phosphorylation, which indicates this region is an important component of FRS2
      and SHC recognition by TrkB. Previously, we had found that the phosphorylation of
      FRS2 induces association of FRS2 and growth factor receptor binding protein 2
      (Grb2). Now, we have intriguing data that indicates BDNF induces association of
      the SH2 domain containing protein tyrosine phosphatase, Shp2, with FRS2.
      Moreover, the PTB association motif of TrkB containing tyrosine 484 is required
      for the BDNF-induced association of Shp2 with FRS2 and the phosphorylation of
      Shp2. These results imply that FRS2 and Shp2 are in a BDNF signaling pathway.
      Shp2 is required for complete MAPK activation by BDNF, as expression of a
      dominant negative Shp2 in cells attenuates BDNF-induced activation of MAPK.
      Moreover, expression of a dominant negative Shp2 attenuates Ras activation
      showing that the protein tyrosine phosphatase is required for complete activation
      of MAPKs by BDNF. In conclusion, Shp2 regulates BDNF signaling through the MAPK
      pathway by regulating either Ras directly or alternatively, by signaling
      components upstream of Ras. Characterization of MAPK signaling controlled by BDNF
      is likely to be required to understand the complex physiological role of BDNF in
      neuronal systems ranging from the regulation of neuronal growth and survival to
      the regulation of synapses.

PMID- 16573650
TI  - Nitric oxide inhibits mitochondrial movement in forebrain neurons associated with
      disruption of mitochondrial membrane potential.
AB  - Nitric oxide (NO) has a number of physiological and pathophysiological effects in
      the nervous system. One target of NO is the mitochondrion, where it inhibits
      respiration and ATP synthesis, which may contribute to NO-mediated neuronal
      injury. Our recent studies suggested that impaired mitochondrial function impairs
      mitochondrial trafficking, which could also contribute to neuronal injury. Here,
      we studied the effects of NO on mitochondrial movement and morphology in primary
      cultures of forebrain neurons using a mitochondrially targeted enhanced yellow
      fluorescent protein. NO produced by two NO donors, papa non-oate and
      diethylamine/NO complex, caused a rapid cessation of mitochondrial movement but
      did not alter morphology. Movement recovered after removal of NO. The effects of
      NO on movement were associated with dissipation of the mitochondrial membrane
      potential. Increasing cGMP levels using 8-bromoguanosine 3',5'-cyclic
      monophosphate, did not mimic the effects on mitochondrial movement. Furthermore,
      1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of NO-induced
      activation of soluble guanylate cyclase, did not block the effects of NO. Thus,
      neither increasing nor decreasing cGMP levels had an effect on mitochondrial
      movement. Based on these data, we conclude that NO is a novel modulator of
      mitochondrial trafficking in neurons, which may act through the inhibition of
      mitochondrial function.

PMID- 16573651
TI  - Susceptibility to rotenone is increased in neurons from parkin null mice and is
      reduced by minocycline.
AB  - Parkinson's disease is a neurodegenerative disorder which is in most cases of
      unknown etiology. Mutations of the Park-2 gene are the most frequent cause of
      familial parkinsonism and parkin knockout (PK-KO) mice have abnormalities that
      resemble the clinical syndrome. We investigated the interaction of genetic and
      environmental factors, treating midbrain neuronal cultures from PK-KO and wild
      type (WT) mice with rotenone (ROT). ROT (0.025-0.1 microm) produced a dose
      dependent selective reduction of tyrosine hydroxylase-immunoreactive cells and of
      other neurons, as shown by the immunoreactivity to microtubule-associated protein
      2 in PK-KO cultures, suggesting that the toxic effect of ROT involved dopamine
      and other types of neurons. Neuronal death was mainly apoptotic and suppressible
      by the caspase inhibitor t-butoxycarbonyl-Asp(OMe)-fluoromethyl ketone (Boc-D
      FMK). PK-KO cultures were more susceptible to apoptosis induced by low doses of
      ROT than those from WT. ROT increased the proportion of astroglia and microglia
      more in PK-KO than in WT cultures. Indomethacin, a cyclo-oxygenase inhibitor,
      worsened the effects of ROT on tyrosine hydroxylase cells, apoptosis and
      astroglial (glial fibrillary acidic protein) cells. N-nitro-L-arginine methyl
      ester, an inhibitor of nitric oxide synthase, increased ROT-induced apoptosis but
      did not change tyrosine hydroxylase-immunoreactive or glial fibrillary acidic
      protein area. Neither indomethacin nor N-nitro-L-arginine methyl ester had any
      effect on the reduction by ROT of the mitochondrial potential as measured by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Microglial NADPH
      oxidase inhibition, however, protected against ROT. The roles of p38 MAPK and
      extracellular signal-regulated kinase signaling pathways were tested by treatment
      with SB20358 and PD98059, respectively. These compounds were inactive in ROT
      naive cultures but PD98059 slightly increased cellular necrosis, as measured by
      lactate dehydrogenase levels, caused by ROT, without changing mitochondrial
      activity. SB20358 increased the mitochondrial failure and lactate dehydrogenase
      elevation induced by ROT. Minocycline, an inhibitor of microglia, prevented the
      dropout of tyrosine hydroxylase and apoptosis by ROT; the addition of microglia
      from PK-KO to WT neuronal cultures increased the sensitivity of dopaminergic
      neurons to ROT. PK-KO mice were more susceptible than WT to ROT and the combined
      effects of Park-2 suppression and ROT reproduced the cellular events observed in
      Parkinson's disease. These events were prevented by minocycline.

PMID- 16573652
TI  - Translational event mediates differential production of tumor necrosis factor
      alpha in hyaluronan-stimulated microglia and macrophages.
AB  - Recent evidence has demonstrated that hyaluronan synthase 2 mRNA is up-regulated
      after brain ischemia. After a cerebral ischemic event, microglia and macrophages
      are the major inflammatory cells and are activated by hyaluronan (HA). However,
      it is unclear how these cells compare with regard to HA responsiveness. We show
      here that peritoneal macrophages and RAW 264.7 macrophages produced more than
      five- and 10-fold more tumor necrosis factor-alpha (TNF-alpha) than primary
      microglia and BV-2 microglia, respectively. Antibody blockade study showed that
      CD44, Toll-like receptor-4 receptor and the receptor for HA-mediated motility
      were responsible for HA-induced TNF-alpha release. Furthermore, HA induced higher
      levels of phosphorylated MAPK in RAW 264.7 cells when compared with BV-2 cells.
      HA-mediated TNF-alpha production required p38 MAPK, extracellular-regulated
      kinase and c-Jun N-terminal kinase phosphorylation in both cell types. The levels
      of HA-induced TNF-alpha mRNA expression in BV-2 cells were only twofold lower
      compared with RAW 264.7 cells, suggesting that a translational event is involved
      in the differential production of TNF-alpha. Western blot analysis revealed that
      HA treatment resulted in more rapid phosphorylation of eukaryotic initiation
      factor 4E-binding protein 1 (4E-BP1) and more effective dissociation of 4E-BP1
      from eukaryotic initiation factor 4E in RAW 264.7 cells than in BV-2 cells.
      Additionally, HA-induced phosphorylation of 4E-BP1 was dependent on MAPK
      signaling, indicating that RAW 264.7 cells exhibited higher levels of
      hyperphosphorylated 4E-BP1 possibly due to the overactivation of MAPK. The
      results suggest that resident microglia and blood-derived monocytes/macrophages
      exhibit differential sensitivities in response to extracellular mediators after
      brain ischemia.

PMID- 16573653
TI  - The 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor pravastatin
      enhances neurite outgrowth in hippocampal neurons.
AB  - Epidemiological studies demonstrate a relationship between statin [3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor] usage and reduced risk
      of developing Alzheimer's disease. To determine whether statins affect neuronal
      development, we treated cultured rat hippocampal neurons with pravastatin. After
      4-48 h of treatment, pravastatin significantly increased the number of neurites
      produced by each cell and caused a corresponding increase in levels of the
      membrane phospholipid phosphatidylcholine. Pravastatin treatment also
      significantly increased neurite length and branching but did not affect cellular
      cholesterol levels. Co-incubation with mevalonate, but not cholesterol, abolished
      the stimulatory effect of pravastatin on neurite outgrowth. Treatment of neurons
      with isoprenoids also abolished the effect of pravastatin on neurite growth,
      suggesting that pravastatin may stimulate neuritogenesis by preventing
      isoprenylation of signaling molecules such as the Rho family of small GTPases. A
      specific inhibitor of geranylgeranylation, but not farnesylation, mimicked the
      stimulatory effect of pravastatin on neuritogenesis. Pravastatin treatment
      significantly decreased levels of membrane-associated RhoA. These data suggest
      that pravastatin treatment increases neurite outgrowth and may do so via
      inhibiting the activity of geranylgeranylated proteins such as RhoA.

PMID- 16573654
TI  - Dopamine release is severely compromised in the R6/2 mouse model of Huntington's
      disease.
AB  - Recently, alterations in dopamine signaling have been implicated in Huntington's
      disease. In this work, dopamine release and uptake was measured in striatal
      slices from the R6/2 transgenic mouse model of Huntington's disease using fast
      scan cyclic voltammetry at carbon-fiber microelectrodes. Dopamine release in
      brain slices from 6-week-old R6/2 mice is substantially reduced (53% of wild
      type), while dopamine uptake is unaffected. In agreement with this, R6/2 mice
      injected with the dopamine uptake inhibitor cocaine exhibited a blunted motor
      activity response (54% of wild type). At 10 weeks of age, an even more dramatic
      motor activity decrease in response to cocaine injection (21% of wild type) was
      observed. Moreover, the pre-drug activity of 10-week-old R6/2 mice was
      significantly reduced (by 37%) compared with 6-week-old R6/2 mice. Striatal
      dopamine release decreased with age, indicating that progressive alterations in
      dopaminergic pathways may affect motor activity. The inhibition constants of
      cocaine and methamphetamine (METH) determined in brain slices differed little
      between genotype or age group, suggesting that the decreased responses to cocaine
      and METH arise from compromised dopamine release rather than differences in
      uptake or drug action. Collectively, these data demonstrate (i) a reduction in
      the ability of dopamine terminals to release dopamine and (ii) the importance of
      this attenuation of release on the motor symptoms of Huntington's disease.

PMID- 16573655
TI  - Regulation of astrocytic glutamate transporter expression by Akt: evidence for a
      selective transcriptional effect on the GLT-1/EAAT2 subtype.
AB  - In the nervous system, astrocytes express different ratios of the two glial
      glutamate transporters, glutamate transporter subtype 1 (GLT-1) and
      glutamate/aspartate transporter (GLAST), but little is known about the signaling
      pathways that independently regulate their expression. Treatment with dibutyryl
      cAMP, epidermal growth factor (EGF) or other growth factors both induces
      expression of GLT-1 and increases expression of GLAST in astrocyte cultures. The
      induction of GLT-1 is correlated with morphological and biochemical changes that
      are consistent with astrocyte maturation. Pharmacological studies suggest that
      phosphatidylinositol 3-kinase (PI-3K) and the nuclear transcription factor-kappaB
      (NF-kappaB) may be involved in the induction of GLT-1 expression. In several
      signaling systems Akt, also known as protein kinase B (PKB), functions downstream
      of PI-3K. In these present studies we used lentiviral vectors engineered to
      express dominant-negative (DN), constitutively active (CA), or null variants of
      Akt to study the possible involvement of Akt in the regulation of GLT-1.
      Expression of DN-Akt attenuated the EGF-dependent induction of GLT-1. Expression
      of CA-Akt caused a dose- and time-dependent increase in GLT-1 protein, increased
      GLT-1 mRNA levels, increased dihydrokainate-sensitive (presumably GLT-1 mediated)
      transport activity, and caused a change in astrocyte morphology to a more
      stellate shape, but had no effect on GLAST protein levels. Finally, the
      expression of CA-Akt increased the expression of a reporter construct containing
      a putative promoter fragment from the human homolog of GLT-1, called EAAT2. From
      these studies, we conclude that Akt induces the expression of GLT-1 through
      increased transcription and that Akt can regulate GLT-1 expression without
      increasing GLAST expression in astrocytes.

PMID- 16573656
TI  - A phosphatidylinositol transfer protein alpha-dependent survival factor protects
      cultured primary neurons against serum deprivation-induced cell death.
AB  - Selective neuronal loss is a prominent feature in both acute and chronic
      neurological disorders. Recently, a link between neurodegeneration and a
      deficiency in the lipid transport protein phosphatidylinositol transfer protein
      alpha (PI-TPalpha) has been demonstrated. In this context it may be of importance
      that fibroblasts overexpressing PI-TPalpha are known to produce and secrete
      bioactive survival factors that protect fibroblasts against UV-induced apoptosis.
      In the present study it was investigated whether the conditioned medium of cells
      overexpressing PI-TPalpha (CMalpha) has neuroprotective effects on primary
      neurons in culture. We show that CMalpha is capable of protecting primary, spinal
      cord-derived motor neurons from serum deprivation-induced cell death. Since the
      conditioned medium of wild-type cells was much less effective, we infer that the
      neuroprotective effect of CMalpha is linked (in part) to the PI-TPalpha-dependent
      production of arachidonic acid metabolites. The neuroprotective activity of
      CMalpha is partly inhibited by suramin, a broad-spectrum antagonist of G-protein
      coupled receptors. Western blot analysis shows that brain cortex and spinal cord
      express relatively high levels of PI-TPalpha, suggesting that the survival factor
      may be produced in neuronal tissue. We propose that the bioactive survival factor
      is implicated in neuronal survival. If so, PI-TPalpha could be a promising target
      to be evaluated in studies on the prevention and treatment of neurological
      disorders.

PMID- 16573657
TI  - Maturation and maintenance of cholinergic medial septum neurons require
      glucocorticoid receptor signaling.
AB  - Glucocorticoids have been shown to influence trophic processes in the nervous
      system. In particular, they seem to be important for the development of
      cholinergic neurons in various brain regions. Here, we applied a genetic approach
      to investigate the role of the glucocorticoid receptor (GR) on the maturation and
      maintenance of cholinergic medial septal neurons between P15 and one year of age
      by using a mouse model carrying a CNS-specific conditional inactivation of the GR
      gene (GRNesCre). The number of choline acetyltransferase and p75NTR immuno
      positive neurons in the medial septum (MS) was analyzed by stereology in controls
      versus mutants. In addition, cholinergic fiber density, acetylcholine release and
      cholinergic key enzyme activity of these neurons were determined in the
      hippocampus. We found that in GRNesCre animals the number of medial septal
      cholinergic neurons was significantly reduced during development. In addition,
      cholinergic cell number further decreased with aging in these mutants. The
      functional GR gene is therefore required for the proper maturation and
      maintenance of medial septal cholinergic neurons. However, the loss of
      cholinergic neurons in the medial septum is not accompanied by a loss of
      functional cholinergic parameters of these neurons in their target region, the
      hippocampus. This pinpoints to plasticity of the septo-hippocampal system, that
      seems to compensate for the septal cell loss by sprouting of the remaining
      neurons.

PMID- 16573658
TI  - Granulocyte-colony stimulating factor is neuroprotective in a model of
      Parkinson's disease.
AB  - We have recently shown that the hematopoietic Granulocyte-Colony Stimulating
      Factor (G-CSF) is neuroprotective in rodent stroke models, and that this action
      appears to be mediated via a neuronal G-CSF receptor. Here, we report that the G
      CSF receptor is expressed in rodent dopaminergic substantia nigra neurons,
      suggesting that G-CSF might be neuroprotective for dopaminergic neurons and a
      candidate molecule for the treatment of Parkinson's disease. Thus, we
      investigated protective effects of G-CSF in 1-methyl-4-phenylpyridinium (MPP+)
      challenged PC12 cells and primary neuronal midbrain cultures, as well as in the
      mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's
      disease. Substantial protection was found against MPP+-induced dopaminergic cell
      death in vitro. Moreover, subcutaneous application of G-CSF at a dose of 40
      microg/Kg body weight daily over 13 days rescued dopaminergic substantia nigra
      neurons from MPTP-induced death in aged mice, as shown by quantification of
      tyrosine hydroxylase-positive substantia nigra cells. Using HPLC, a corresponding
      reduction in striatal dopamine depletion after MPTP application was observed in G
      CSF-treated mice. Thus our data suggest that G-CSF is a novel therapeutic
      opportunity for the treatment of Parkinson's disease, because it is well
      tolerated and already approved for the treatment of neutropenic conditions in
      humans.

PMID- 16573660
TI  - Workforce: the new core curriculum for medical schools.

PMID- 16573661
TI  - Crafting the reflective lifelong learner: why, what and how.

PMID- 16573659
TI  - Post-translational regulation of EAAT2 function by co-expressed ubiquitin ligase
      Nedd4-2 is impacted by SGK kinases.
AB  - The human excitatory amino acid transporter (EAAT)2 is the major glutamate
      carrier in the mammalian CNS. Defective expression of the transporter results in
      neuroexcitotoxicity that may contribute to neuronal disorders such as amyotrophic
      lateral sclerosis (ALS). The serum and glucocorticoid inducible kinase (SGK) 1 is
      expressed in the brain and is known to interact with the ubiquitin ligase Nedd4-2
      to modulate membrane transporters and ion channels. The present study aimed to
      investigate whether SGK isoforms and the related kinase, protein kinase B (PKB),
      regulate EAAT2. Expression studies in Xenopus oocytes demonstrated that glutamate
      induced inward current (IGLU) was stimulated by co-expression of SGK1, SGK2, SGK3
      or PKB. IGLU is virtually abolished by Nedd4-2, an effect abrogated by additional
      co-expression of either kinase. The kinases diminish the effect through Nedd4-2
      phosphorylation without altering Nedd4-2 protein abundance. SGKs increase the
      transporter maximal velocity without significantly affecting substrate affinity.
      Similar to glutamate-induced currents, [3H] glutamate uptake and cell surface
      abundance of the transporter were increased by the SGK isoforms and down
      regulated by the ubiquitin ligase Nedd4-2. In conclusion, all three SGK isoforms
      and PKB increase EAAT2 activity and plasma membrane expression and thus, may
      participate in the regulation of neuroexcitability.

PMID- 16573662
TI  - Using qualitative interviews within medical education research: why we must raise
      the 'quality bar'.

PMID- 16573663
TI  - Perspectives on the scholarship of teaching.

PMID- 16573664
TI  - A plea for new psychometric models in educational assessment.
AB  - OBJECTIVE: To describe the weaknesses of the current psychometric approach to
      assessment as a scientific model. DISCUSSION: The current psychometric model has
      played a major role in improving the quality of assessment of medical competence.
      It is becoming increasingly difficult, however, to apply this model to modern
      assessment methods. The central assumption in the current model is that medical
      competence can be subdivided into separate measurable stable and generic traits.
      This assumption has several far-reaching implications. Perhaps the most important
      is that it requires a numerical and reductionist approach, and that aspects such
      as fairness, defensibility and credibility are by necessity mainly translated
      into reliability and construct validity. These approaches are more and more
      difficult to align with modern assessment approaches such as mini-CEX, 360-degree
      feedback and portfolios. This paper describes some of the weaknesses of the
      psychometric model and aims to open a discussion on a conceptually different
      statistical approach to quality of assessment. FUTURE DIRECTIONS: We hope that
      the discussion opened by this paper will lead to the development of a
      conceptually different statistical approach to quality of assessment. A
      probabilistic or Bayesian approach would be worth exploring.

PMID- 16573665
TI  - Caring for a common future: medical schools' social accountability.
AB  - ORIGINS AND CONTEXT: The concept of 'the social accountability of medical
      schools' is moving from the peripheral preoccupation of a few to a more central
      concern of medical schools themselves. Born of concerns about the professionalism
      and relevance of both the institutions and their graduates, it is seen
      increasingly as an urgent call to focus the considerable social resources vested
      in academic health science institutions on addressing the priority health
      concerns of the societies they serve. For a profession embedded in an ethos of
      service, this would seem an obvious transition. However, as with any movement
      towards transformative change, it runs the risk of being more mantra and rhetoric
      than mandate and responsibility. NEEDED RESPONSE: Proceeding from the assumption
      that good intentions alone are not enough, this paper seeks to outline the
      historical development and some current expression of the concept throughout the
      world. The sadly divergent wealth and health status of modern societies calls for
      very different actions by medical schools across the spectrum from the least
      endowed to the wealthiest of schools. In a profession claiming centuries of
      cohesive commitment to the welfare of others, it is increasingly urgent that the
      current generation of medical educators converge on a relevant set of principles
      and coherent activities. TOOLS FOR THE TASK: While recognising that they are
      closely intertwined, the paper outlines the difference between the social
      accountability of the institutions themselves and the social accountability of
      the graduates they produce. It outlines both individual examples and the
      international initiatives that are fostering and facilitating institutional
      collaborations to bring both progress and optimism to this daunting task. It
      provides connections to practical resources for those who are committed to that
      task. Other papers in this series add further practical insights into the central
      role that medical educators must play if we are to fulfil the responsibilities we
      carry with the privilege of our profession.

PMID- 16573666
TI  - The qualitative research interview.
AB  - BACKGROUND: Interviews are among the most familiar strategies for collecting
      qualitative data. The different qualitative interviewing strategies in common use
      emerged from diverse disciplinary perspectives resulting in a wide variation
      among interviewing approaches. Unlike the highly structured survey interviews and
      questionnaires used in epidemiology and most health services research, we examine
      less structured interview strategies in which the person interviewed is more a
      participant in meaning making than a conduit from which information is retrieved.
      PURPOSE: In this article we briefly review the more common qualitative interview
      methods and then focus on the widely used individual face-to-face in-depth
      interview, which seeks to foster learning about individual experiences and
      perspectives on a given set of issues. We discuss methods for conducting in-depth
      interviews and consider relevant ethical issues with particular regard to the
      rights and protection of the participants.

PMID- 16573667
TI  - Medical students' perceptions of their learning about the doctor-patient
      relationship: a qualitative study.
AB  - OBJECTIVE: To describe and discuss Year 5 medical students' perceptions of their
      own learning about the doctor-patient relationship. METHODS: We carried out a
      qualitative study of semi-structured interviews with 16 Year 5 medical students
      using 3-way analysis at the School of Medicine, Federal University of Sao Paulo,
      Sao Paulo, Brazil. RESULTS: For experiences at the pre-clinical stage, the
      subcategories were: positive aspects of the medical psychology course; great
      distance between theory and reality, and strong desire for clinical practice. For
      experiences at the clinical stage, the subcategories were: demand for
      opportunities to discuss the doctor-patient relationship; teachers as either role
      models or anti-models; clinical situations favourable for developing empathic
      relationships, and clinical situations unfavourable for developing empathic
      relationships. For views about future experiences, the subcategories were:
      apprehension about ethical behaviour; anxiety about handling patients'
      psychosocial characteristics, and fear of professional ethics cases or legal
      action. DISCUSSION: To compensate for the lack of practical activities during the
      pre-clinical stage, students search for extracurricular activities that often
      overload them. Because teachers function as professional role models, their
      attitudes towards patients have great importance. Students fear not being able to
      maintain their empathic capacity in the future because of work-related issues.
      Knowledge of the psychological aspects of the doctor-patient relationship helps
      students to comprehend their experiences. Gradual contact between student and
      medical practice from the beginning of the course is advised. It should be
      followed by interdisciplinary discussions that deal with the technical aspects of
      cases and the doctor-patient relationship.

PMID- 16573669
TI  - Participation in the workforce by Australian medical graduates.
AB  - OBJECTIVE: To investigate workforce participation patterns among Australian
      medical graduates and the extent of cohort differences in these patterns. DESIGN:
      We carried out a retrospective longitudinal cohort study, with data collected by
      postal survey on current occupation, location, absences from the workforce and
      occupation since graduation. PARTICIPANTS: Graduates who had completed their
      basic medical training at Monash University, Melbourne, Australia, in 1980, 1985,
      1990 and 1995 were invited to participate (n = 546); 368 took part in the study
      (69%). OUTCOME MEASURES: The proportion of graduates in the Australian medical
      workforce, the equivalent full-time contribution to the Australian medical
      workforce, and the proportion taking temporary absences from the workforce were
      determined. RESULTS: The rate of participation in the Australian medical
      workforce was 96% 2 years after graduation. It then declined to reach 85% by 10
      years and regained slightly to reach 88% by 15 years after graduation. There was
      no indication that the 1995 cohort made a lower contribution to the Australian
      medical workforce than the earlier cohorts in their first 7 years after
      graduation. CONCLUSION: Although there are few indications of differences between
      these cohorts during the first 7 years after graduation, the main contributing
      factors to losses from the Australian medical workforce -- medical work overseas
      and parental leave -- do not exert their maximum influence until a later time
      point. Longitudinal cohort data are essential for monitoring trends in medical
      workforce participation and hence for effective workforce planning.

PMID- 16573668
TI  - Undergraduate ethics teaching: revisiting the Consensus Statement.
AB  - OBJECTIVE: To determine whether the recommendations of the Consensus Statement
      published 7 years ago have been implemented. DESIGN: Postal questionnaire survey
      of 28 UK medical schools. METHODS: A survey was sent to the lead individual for
      teaching and learning at each medical school. This questionnaire inquired about
      the undergraduate ethics and law curriculum, including its design, teaching,
      assessment, staffing, and individuals' hopes and concerns for the future. MAIN
      OUTCOME MEASURES: Information relating to undergraduate ethics teaching in UK
      medical schools. RESULTS: Significant changes in the teaching and assessment of
      medical ethics and law that could be directly attributed to the Consensus
      Statement were identified. Whilst most schools covered all 12 recommended topics
      in their curriculum, only 3 felt all the topics were covered thoroughly and 3
      schools said at least 1 topic was not covered at all. Only 16 schools identified
      1 or more full-time academics who took direct responsibility for ensuring
      undergraduate medical students learnt about ethics; these were usually at
      lecturer grade. CONCLUSIONS: The Consensus Statement has had a significant impact
      on the teaching of undergraduate ethics but, even 7 years on, not all its
      recommendations have been implemented fully.

PMID- 16573671
TI  - Views, behaviours and perceived staff development needs of doctors and surgeons
      regarding learners in outpatient clinics.
AB  - INTRODUCTION: The need to use outpatient clinics as a major learning environment
      in hospitals for students and doctors-in-training is clear. However, consultant
      supervisors perceive major barriers to this and continue to rely heavily on
      traditional inpatient learning. This quantitative study examines what approaches
      consultant supervisors employ in outpatient learning, together with what they
      perceive themselves to use and what they would value in further training.
      METHODS: We observed learning episodes for students and doctors-in-training in
      medical and surgical clinics. A questionnaire on outpatient teaching was also
      sent to consultant doctors and surgeons. This was based on these observations and
      focus groups with students and doctors-in-training. RESULTS: There was an overall
      survey response rate of 62% (194/311). The dominant forms of learning we observed
      were 'arms-length' supervision for doctors-in-training and 'modelling' for
      students. Only 7% of learning episodes involved a doctor-in-training doing
      something under direct supervision. In contrast to the observation results,
      consultants considered that students and doctors-in-training received a lot of
      direct supervision and interaction. For example, 45% considered that doctors-in
      training 'may see patients with me in a joint consultation'. Only 30% of
      respondents would be interested in staff development in learning in outpatient
      clinics. CONCLUSIONS: Although consultants reported that they frequently used an
      active approach to learning in outpatient clinics, modelling was used
      predominantly for students and arms-length supervision was used for doctors-in
      training.

PMID- 16573670
TI  - A study of a multi-source feedback system for international medical graduates
      holding defined licences.
AB  - OBJECTIVE: To develop and assess the feasibility and psychometric properties of
      multi-source feedback questionnaires to monitor international medical graduates
      practising in Canada under 'defined' licences. METHOD: Four questionnaires
      (patient, co-worker, colleague and self) were developed and administered in 2
      phases through paper-based and telephone or Internet formats. Reliability was
      assessed with Cronbach's alpha and generalisability coefficient analyses.
      Validity was established through mean ratings, 'unable to respond' rates and
      factor analyses. RESULTS: A total of 37 doctors participated in the 2 phases.
      Overall response rates were 70% for patients, 86% for co-workers, 72% for medical
      colleagues and 92% for self, with response rates higher for the paper-based
      format than the Internet and phone formats. The instruments had high internal
      consistency reliability, with Cronbach's alphas of 0.83 for self-assessment and >
      0.90 for the other instruments. The generalisability coefficients were Ep(2) =
      0.71 for 25 patients on a 13-item survey, Ep(2) = 0.59 for 8 co-workers on a 13
      item survey, and Ep(2) = 0.67 for 8 colleagues on a 21-item questionnaire. The
      range of mean scores was narrow (between 4 and 5) for all items and all surveys.
      The factor analyses identified that 2 factors accounted for 70% or more of the
      variance for the patient and colleague surveys and 60% of the variance for the co
      worker survey. CONCLUSION: These data suggest that the instruments have
      reasonable psychometric properties. Traditional survey methods (i.e. paper-based)
      yielded better results than Internet or phone methods for this group of doctors.

PMID- 16573672
TI  - The training/service continuum: exploring the training/service balance of senior
      house officer activities.
AB  - BACKGROUND: The continued reduction in junior doctors' hours in the UK has made
      it necessary to re-examine traditional assumptions about the synonymous natures
      of training and service. This paper researches senior house officers' (SHOs)
      perceptions of 'service' and 'training', with reference to where they place
      activities along the training/service continuum, and the factors that lead them
      to classify these activities in the way they do. METHODS: Questionnaires were
      sent to all identified SHOs at Plymouth Hospitals NHS Trust (40% response rate).
      Three focus groups were held with 5 SHOs, 3 consultants and 2 clinical tutors.
      Quantitative data derived from the questionnaires were analysed using spss.
      Qualitative data collected in the focus groups was coded with the aid of n6,
      which facilitated the thematic analysis of transcripts. RESULTS: Analysis of the
      quantitative data allowed the construction of the training/service continuum
      diagram. Identified factors affecting the perceived training/service balance of
      SHO activities included: frequency, time, type and nature of work, number of
      patients, supervision, interaction, other commitments, purpose and focus of the
      activity, the individual trainee and trainer, and experience and competence.
      DISCUSSION: It is no longer appropriate to assume that all junior doctor
      activities represent either training or service individually: activities are
      perceived differently along the training/service continuum depending on their
      execution and their relation to the SHOs' learning curves. Within the reduced
      hours framework, it is necessary to match this balance to experience, in order
      for both training and service requirements to be satisfied.

PMID- 16573673
TI  - The reliability and validity of a matrix to assess the completed reflective
      personal development plans of general practitioners.
AB  - INTRODUCTION: We wished to determine whether assessors could make reliable and
      valid judgements about the quality of completed reflective personal development
      plans (PDPs) for the purpose of accrediting UK general practitioners (GPs) for a
      postgraduate education allowance using a marking matrix, and secondly, to plan a
      feasible model of PDP assessment in the context of forthcoming GP
      appraisal/revalidation that would overcome the main sources of error identified
      from this study. METHODS: Within generalisability theory, a variance components
      analysis on PDP scores estimated reliability and the effect on them of varying,
      for example, the number of assessors. We investigated the construct validity of
      the matrix through its internal consistency and detection of differences in the
      quality of PDPs. RESULTS: For a single PDP and one assessor, 37.6% of the
      variance in scores was due to true differences in the quality of the PDP. Between
      5 and 7 PDP assessors are needed to achieve summative reliability of greater than
      0.8. While increasing the number of judges is important, reliability could also
      be improved by addressing assessor subjectivity. Construct validity was
      demonstrated, as the matrix distinguished between good, satisfactory and poor
      PDPs, and it had good internal consistency. CONCLUSION: PDP assessment has
      reasonable summative characteristics for the purpose of assessing GPs' reflective
      continuing professional development. If doctors could include their PDPs within
      their revalidation folders as evidence of their reflections on pursuing better
      clinical performance, we have described a reliable, valid and feasible method of
      external assessment.

PMID- 16573674
TI  - Participants' opinions on the usefulness of a teaching portfolio.
AB  - BACKGROUND: Whether teaching portfolios achieve their aim of stimulating
      teachers' professional development is favourably affected by the incorporation of
      a balanced structure and effective social interactions, such as coaching. We
      explored teachers' experiences with a teaching portfolio that was structured by
      teaching roles, portfolio assignments and conversation protocols. The related
      social interactions consisted of meetings with peers and personal coaches.
      Teachers' and coaches' opinions were sought about the benefits and the enabling
      and disabling factors of the portfolio structure and the social interactions
      involved. METHOD: Five teachers and their personal coaches were individually
      interviewed about their experiences with the portfolio. Protocols were analysed
      using a top-down strategy. RESULTS: The teaching roles were helpful in analysing
      teaching, but the assignments and the conversation protocols were too detailed
      and directive. The social interactions were perceived as very valuable for
      professional development, particularly the meetings with personal coaches.
      CONCLUSIONS: The portfolio structure and social interactions, especially personal
      coaching, appeared to be helpful for teachers in analysing their teaching
      practice. The assignments and protocols, however, were too detailed and
      directive. This may be resolved by using assignments and conversation protocols
      more flexibly and enabling adjustment to personal learning needs. The high
      appreciation of personal coaching might be related to the freedom for teachers to
      choose their own coach. The results can be used by portfolio designers as
      guidelines for how to achieve a balanced structure and effective social
      interactions and how these might be combined to increase the benefits of working
      with a portfolio to teachers.

PMID- 16573675
TI  - Students' views of reflective learning techniques: an efficacy study at a UK
      medical school.
AB  - OBJECTIVE: To describe the effects of a voluntary intervention using reflective
      learning techniques on students' learning. DESIGN: An interventional study with
      reflective learning techniques offered to medical students. SETTING: Year 3 of
      undergraduate medicine at Cardiff University where the curriculum is integrated
      with early clinical contact. PARTICIPANTS: All 232 Year 3 students were invited
      to participate. A total of 65 attended an introductory lecture. After the lecture
      35 students agreed to take part; 15 of these subsequently dropped out (some
      before attending tutorial groups, others after taking part for some weeks).
      INTERVENTIONS: Participants kept learning journals for 2 terms and attended
      fortnightly, facilitated tutorial groups where they discussed their reflective
      journal entries. Main outcome measures were qualitative interviews and
      examination results. RESULTS: Interviews were carried out with 19 full
      participants, 4 initial participants and 7 non-participants. Participants
      perceived that they gained a greater ability to identify learning objectives and
      to integrate learning. The tutorial groups encouraged students to compare
      progress with their peers. Some students did not take part because they thought
      that the large factual content of the curriculum would make reflective learning
      less useful. There were no differences between the groups in examination results.
      CONCLUSIONS: Students among the small, self-selected group of participants were
      better able to identify what they needed to learn although there was no
      improvement in examination results. Students appear unlikely to take up voluntary
      reflective learning if they do not think it relates to the curriculum and
      assessments. Student culture exerts a potent effect on willingness to attend
      extra tutorial groups.

PMID- 16573676
TI  - Comparing the distress of American and Israeli medical students studying in
      Israel during a period of terror.
AB  - INTRODUCTION: Medical school is a very stressful environment with multiple
      sources of stress, including academic, social and other issues. International
      medical students are exposed to additional stressors such as homesickness and
      culture shock. METHODS: In order to assess the influence of cultural background
      on the level of perceived distress, we examined Israeli and American students
      studying at the same university during a period of terror. RESULTS: We found
      clear differences between the 2 groups of students, with Americans reporting a
      higher level of anxiety and a poorer level of social functioning than the
      Israelis. Although there was no significant difference between the 2 groups in
      terms of their sense of safety, the American students reported a higher level of
      fear and more change in their daily activities to a greater extent than did the
      Israelis. CONCLUSIONS: These findings underscore the effect of culture on
      students' responses to the same stressful stimuli and to a perceived dangerous
      environment. Faculty needs to be aware that cultural factors may affect students'
      adjustment to the medical school environment.

PMID- 16573677
TI  - What is life? The paradigm of DNA and protein cooperation at high local
      concentrations.
AB  - Many chemical reactions need high concentrations of the molecules involved in
      order to work efficiently. It is usually impossible for the cell to achieve the
      necessary high concentrations of all relevant molecules in unconfined solutions
      but this becomes possible if the high concentration is restricted around a
      relevant molecule. High local concentrations of interacting molecules have been
      observed many times in many different biological systems. The examples of Lac and
      Lambda repressors of Escherichia coli are presented and discussed here as useful
      paradigms of mechanisms for achieving high local concentrations of interacting
      protein protomers.

PMID- 16573678
TI  - A bacterium that has three pathways to regulate membrane lipid fluidity.
AB  - Well-studied bacteria such as Bacillus subtilis and Escherichia coli each have
      only a single pathway for synthesis of the unsaturated fatty acids required to
      make functional membrane lipids. In marked contrast, unsaturated fatty acid
      synthesis in Pseudomonas aeruginosa proceeds by three distinct pathways.

PMID- 16573679
TI  - Two aerobic pathways for the formation of unsaturated fatty acids in Pseudomonas
      aeruginosa.
AB  - The double bond in anaerobic unsaturated fatty acid (UFA) biosynthesis is
      introduced by the FabA dehydratase/isomerase of the bacterial type II fatty acid
      biosynthetic pathway. A DeltafabA mutant of Pseudomonas aeruginosa grew
      aerobically, but required a UFA supplement for anaerobic growth. Wild-type cells
      produced 18:1Delta11 as the principal UFA, whereas the DeltafabA strain produced
      only 16:1Delta9. The double bond in the 16:1Delta9 was introduced after
      phospholipid formation and was localized in the sn-2 position. Two predicted
      membrane proteins, DesA and DesB, possessed the conserved histidine clusters
      characteristic of fatty acid desaturases. The DeltafabADeltadesA double mutant
      required exogenous fatty acids for growth but the DeltafabAdesB double mutant did
      not. Exogenous stearate was converted to 18:1Delta9 and supported the growth of
      DeltafabADeltadesA double mutant. A DeltafabADeltadesAdesB triple mutant was
      unable to desaturate exogenous stearate and was an UFA auxotroph. We detected a
      2.5-fold increase in desA expression in DeltafabA mutants, whereas desB
      expression was derepressed by the deletion of the gene encoding a transcriptional
      repressor DesT. These data add two aerobic desaturases to the enzymes used for
      fatty acid metabolism in proteobacteria: DesA, a 2-position phospholipid Delta9
      desaturase that supplements the anaerobic FabA pathway, and DesB, an inducible
      acyl-CoA Delta9-desaturase whose expression is repressed by DesT.

PMID- 16573680
TI  - Characterizing the flagellar filament and the role of motility in bacterial prey
      penetration by Bdellovibrio bacteriovorus.
AB  - The predatory bacterium Bdellovibrio bacteriovorus swims rapidly by rotation of a
      single, polar flagellum comprised of a helical filament of flagellin monomers,
      contained within a membrane sheath and powered by a basal motor complex.
      Bdellovibrio collides with, enters and replicates within bacterial prey, a
      process previously suggested to firstly require flagellar motility and then
      flagellar shedding upon prey entry. Here we show that flagella are not always
      shed upon prey entry and we study the six fliC flagellin genes of B.
      bacteriovorus, finding them all conserved and expressed in genome strain HD100
      and the widely studied lab strain 109J. Individual inactivation of five of the
      fliC genes gave mutant Bdellovibrio that still made flagella, and which were
      motile and predatory. Inactivation of the sixth fliC gene abolished normal
      flagellar synthesis and motility, but a disordered flagellar sheath was still
      seen. We find that this non-motile mutant was still able to predate when directly
      applied to lawns of YFP-labelled prey bacteria, showing that flagellar motility
      is not essential for prey entry but important for efficient encounters with prey
      in liquid environments.

PMID- 16573681
TI  - Phosphoenolpyruvate synthetase and pyruvate, phosphate dikinase of Thermoproteus
      tenax: key pieces in the puzzle of archaeal carbohydrate metabolism.
AB  - The interconversion of phosphoenolpyruvate and pyruvate represents an important
      control point of the Embden-Meyerhof-Parnas (EMP) pathway in Bacteria and
      Eucarya, but little is known about this site of regulation in Archaea. Here we
      report on the coexistence of phosphoenolpyruvate synthetase (PEPS) and the first
      described archaeal pyruvate, phosphate dikinase (PPDK), which, besides pyruvate
      kinase (PK), are involved in the catalysis of this reaction in the
      hyperthermophilic crenarchaeote Thermoproteus tenax. The genes encoding T. tenax
      PEPS and PPDK were cloned and expressed in Escherichia coli, and the enzymic and
      regulatory properties of the recombinant gene products were analysed. Whereas
      PEPS catalyses the unidirectional conversion of pyruvate to phosphoenolpyruvate,
      PPDK shows a bidirectional activity with a preference for the catabolic reaction.
      In contrast to PK of T. tenax, which is regulated on transcript level but
      exhibits only limited regulatory potential on protein level, PEPS and PPDK
      activities are modulated by adenosine phosphates and intermediates of the
      carbohydrate metabolism. Additionally, expression of PEPS is regulated on
      transcript level in response to the offered carbon source as revealed by Northern
      blot analyses. The combined action of the differently regulated enzymes PEPS,
      PPDK and PK represents a novel way of controlling the interconversion of
      phosphoenolpyruvate and pyruvate in the reversible EMP pathway, allowing short
      term and long-term adaptation to different trophic conditions. Comparative
      genomic analyses indicate the coexistence of PEPS, PPDK and PK in other Archaea
      as well, suggesting a similar regulation of the carbohydrate metabolism in these
      organisms.

PMID- 16573682
TI  - Changes in flagellin glycosylation affect Campylobacter autoagglutination and
      virulence.
AB  - Analysis of the complete flagellin glycosylation locus of Campylobacter jejuni
      strain 81-176 revealed a less complex genomic organization than the corresponding
      region in the genome strain, C. jejuni NCTC 11168. Twenty-four of the 45 genes
      found between Cj1293 and Cj1337 in NCTC 11168 are missing in 81-176. Mutation of
      six new genes, in addition to three previously reported, resulted in a non-motile
      phenotype, consistent with a role in synthesis of pseudaminic acid (PseAc) or
      transfer of PseAc to flagellin. Mutation of Cj1316c or pseA had been shown to
      result in loss of the acetamidino form of pseudaminic acid (PseAm). Mutation of a
      second gene also resulted in loss of PseAm, as well as a minor modification that
      appears to be PseAm extended with N-acetyl-glutamic acid. Previously described
      mutants in C. jejuni 81-176 and Campylobacter coli VC167 that produced flagella
      lacking PseAm or PseAc failed to autoagglutinate. This suggests that interactions
      between modifications on adjacent flagella filaments are required for
      autoagglutination. Mutants (81-176) defective in autoagglutination showed a
      modest reduction in adherence and invasion of INT407 cells. However, there was a
      qualitative difference in binding patterns to INT407 cells using GFP-labelled 81
      176 and mutants lacking PseAm. A mutant lacking PseAm was attenuated in the
      ferret diarrhoeal disease model.

PMID- 16573683
TI  - The Mycobacterium tuberculosis PhoPR two-component system regulates genes
      essential for virulence and complex lipid biosynthesis.
AB  - Two-component signal transduction systems (2-CS) play an important role in
      bacterial pathogenesis. In the work presented here, we have studied the effects
      of a mutation in the Mycobacterium tuberculosis (Mtb) PhoPR 2-CS on the
      pathogenicity, physiology and global gene expression of this bacterial pathogen.
      Disruption of PhoPR causes a marked attenuation of growth in macrophages and mice
      and prevents growth in low-Mg2+ media. The inability to grow in THP-1 macrophages
      can be partially overcome by the addition of excess Mg2+ during infection. Global
      transcription assays demonstrate PhoP is a positive transcriptional regulator of
      several genes, but do not support the hypothesis that the Mtb PhoPR system is
      sensing Mg2+ starvation, as is the case with the Salmonella typhimurium PhoPQ 2
      CS. The genes that were positively regulated include those found in the pks2 and
      the msl3 gene clusters that encode enzymes for the biosynthesis of sulphatides
      and diacyltrehalose and polyacyltrehalose respectively. Complementary biochemical
      studies, in agreement with recent results from another group, indicate that these
      complex lipids are also absent from the phoP mutant, and the lack of these
      components in its cell envelope may indirectly cause the mutant's high-Mg2+
      growth requirement. The experiments reported here provide functional evidence for
      the PhoPR 2-CS involvement in Mtb pathogenesis, and they suggest that a major
      reason for the attenuation observed in the phoP mutant is the absence of certain
      complex lipids that are known to be important for virulence.

PMID- 16573684
TI  - Cyclic-diGMP signal transduction systems in Vibrio cholerae: modulation of
      rugosity and biofilm formation.
AB  - Cyclic di-guanylic acid (c-diGMP) is a second messenger that modulates the cell
      surface properties of several microorganisms. Concentrations of c-diGMP in the
      cell are controlled by the opposing activities of diguanylate cyclases and
      phosphodiesterases, which are carried out by proteins harbouring GGDEF and EAL
      domains respectively. In this study, we report that the cellular levels of c
      diGMP are higher in the Vibrio cholerae rugose variant compared with the smooth
      variant. Modulation of cellular c-diGMP levels by overexpressing proteins with
      GGDEF or EAL domains increased or decreased colony rugosity respectively. Several
      genes encoding proteins with either GGDEF or EAL domains are differentially
      expressed between the two V. cholerae variants. The generation and
      characterization of null mutants of these genes (cdgA-E, rocS and mbaA) revealed
      that rugose colony formation, exopolysaccharide production, motility and biofilm
      formation are controlled by their action. Furthermore, epistasis analysis
      suggested that cdgC, rocS and mbaA act in convergent pathways to regulate the
      phenotypic properties of the rugose and smooth variants, and are part of the
      VpsR, VpsT and HapR signal transduction pathway.

PMID- 16573685
TI  - The enteropathogenic Escherichia coli type III secretion system effector Map
      binds EBP50/NHERF1: implication for cell signalling and diarrhoea.
AB  - Enteropathogenic Escherichia coli (EPEC) is the single most important contributor
      to child diarrhoea in developing countries. Nevertheless, the mechanism
      responsible for EPEC diarrhoea remains elusive. Using the yeast two-hybrid system
      to determine the target host cell protein of the EPEC type III secretion system
      effector Map led to identification of ezrin/radixin/moesin (ERM)-binding
      phosphoprotein 50 (EBP50), also known as Na+/H+ exchanger regulatory factor 1
      (NHERF1). Protein interaction is mediated by the carboxy-terminal Thr-Arg-Leu
      (TRL) motif of Map and the PSD-95/Disk-large/ZO-1 domain 1 (PDZ1) of
      EBP50/NHERF1. Although EBP50/NHERF1 is recruited to site of EPEC adhesion in a
      Map-independent mechanism, co-immunoprecipitation and immunostaining revealed
      that Map binds to, induces proteolysis of, and colocalizes with EBP50/NHERF1
      during infection of cultured epithelial cells. The TRL motif of Map was involved
      in Map-induced filopodia formation and brush border elongation on infected HeLa
      and Caco-2 cells respectively. As EBP50/NHERF1 regulates ion channels in the
      intestine we assessed the involvement of Map in diarrhoea using the Citrobacter
      rodentium mouse model of EPEC. We report significantly greater diarrhoea
      following infections with wild-type C. rodentium compared with C.
      rodentiumDeltamap. These results provide new insights into the mechanisms of EPEC
      diarrhoea.

PMID- 16573686
TI  - Analysis of the requirements for pilus biogenesis at the outer membrane usher and
      the function of the usher C-terminus.
AB  - Uropathogenic strains of Escherichia coli assemble type 1 and P pili to colonize
      the bladder and kidney respectively. These pili are prototype structures
      assembled by the chaperone/usher secretion pathway. In this pathway, a
      periplasmic chaperone works together with an outer membrane (OM) usher to control
      the folding of pilus subunits, their assembly into a pilus fibre and secretion of
      the fibre to the cell surface. The usher serves as the assembly and secretion
      platform in the OM. The usher has distinct functional domains, with the N
      terminus providing the initial targeting site for chaperone-subunit complexes and
      the C-terminus required for subsequent stages of pilus biogenesis. In this study,
      we investigated the molecular interactions occurring at the usher during pilus
      biogenesis and the function of the usher C-terminus. We provide genetic and
      biochemical evidence that the usher functions as a complex in the OM and that
      interaction of the pilus adhesin with the usher is critical to prime the usher
      for pilus biogenesis. Analysis of C-terminal truncation and substitution mutants
      of the P pilus usher PapC demonstrated that the C-terminus is required for proper
      binding of chaperone-subunit complexes to the usher and plays an important role
      in assembly of complete pili.

PMID- 16573687
TI  - Three-dimensional structure of Mycoplasma pneumoniae's attachment organelle and a
      model for its role in gliding motility.
AB  - While most motile bacteria propel themselves with flagella, other mechanisms have
      been described including retraction of surface-attached pili, secretion of
      polysaccharides, or movement of motors along surface protein tracks. These have
      been referred to collectively as forms of 'gliding' motility. Despite being
      simultaneously one of the smallest and simplest of all known cells, Mycoplasma
      pneumoniae builds a surprisingly large and complex cell extension known as the
      attachment organelle that enables it to glide. Here, three-dimensional images of
      the attachment organelle were produced with unprecedented clarity and
      authenticity using state-of-the-art electron cryotomography. The attachment
      organelle was seen to contain a multisubunit, jointed, dynamic motor much larger
      than a flagellar basal body and comparable in complexity. A new model for its
      function is proposed wherein inchworm-like conformational changes of its electron
      dense core are leveraged against a cytoplasmic anchor and transmitted to the
      surface through layered adhesion proteins.

PMID- 16573688
TI  - Yeast ribosomal P0 protein has two separate binding sites for P1/P2 proteins.
AB  - The ribosome has a distinct lateral protuberance called the stalk; in eukaryotes
      it is formed by the acidic ribosomal P-proteins which are organized as a
      pentameric entity described as P0-(P1-P2)(2). Bilateral interactions between P0
      and P1/P2 proteins have been studied extensively, however, the region on P0
      responsible for the binding of P1/P2 proteins has not been precisely defined.
      Here we report a study which takes the current knowledge of the P0 - P1/P2
      protein interaction beyond the recently published information. Using truncated
      forms of P0 protein and several in vitro and in vivo approaches, we have defined
      the region between positions 199 and 258 as the P0 protein fragment responsible
      for the binding of P1/P2 proteins in the yeast Saccharomyces cerevisiae. We show
      two short amino acid regions of P0 protein located at positions 199-230 and 231
      258, to be responsible for independent binding of two dimers, P1A-P2B and P1B-P2A
      respectively. In addition, two elements, the sequence spanning amino acids 199
      230 and the P1A-P2B dimer were found to be essential for stalk formation,
      indicating that this process is dependent on a balance between the P1A-P2B dimer
      and the P0 protein.

PMID- 16573689
TI  - PerR controls Mn-dependent resistance to oxidative stress in Neisseria
      gonorrhoeae.
AB  - In previous studies it has been established that resistance to superoxide by
      Neisseria gonorrhoeae is dependent on the accumulation of Mn(II) ions involving
      the ABC transporter, MntABC. A mutant strain lacking the periplasmic binding
      protein component (MntC) of this transport system is hypersensitive to killing by
      superoxide anion. In this study the mntC mutant was found to be more sensitive to
      H2O2 killing than the wild-type. Analysis of regulation of MntC expression
      revealed that it was de-repressed under low Mn(II) conditions. The N. gonorrhoeae
      mntABC locus lacks the mntR repressor typically found associated with this locus
      in other organisms. A search for a candidate regulator of mntABC expression
      revealed a homologue of PerR, a Mn-dependent peroxide-responsive regulator found
      in Gram-positive organisms. A perR mutant expressed more MntC protein than wild
      type, and expression was independent of Mn(II), consistent with a role for PerR
      as a repressor of mntABC expression. The PerR regulon of N. gonorrhoeae was
      defined by microarray analysis and includes ribosomal proteins, TonB-dependent
      receptors and an alcohol dehydrogenase. Both the mntC and perR mutants had
      reduced intracellular survival in a human cervical epithelial cell model.

PMID- 16573690
TI  - Cholera stool bacteria repress chemotaxis to increase infectivity.
AB  - Factors that enhance the transmission of pathogens are poorly understood. We show
      that Vibrio cholerae shed in human 'rice-water' stools have a 10-fold lower oral
      infectious dose in an animal model than in vitro grown V. cholerae, which may aid
      in transmission during outbreaks. Furthermore, we identify a bacterial factor
      contributing to this enhanced infectivity: The achievement of a transient motile
      but chemotaxis-defective state upon shedding from humans. Rice-water stool V.
      cholerae have reduced levels of CheW-1, which is essential for chemotaxis, and
      were consequently shown to have a chemotaxis defect when tested in capillary
      assays. Through mutational analyses, such a state is known to enhance the
      infectivity of V. cholerae. This is the first report of a pathogen altering its
      chemotactic state in response to human infection in order to enhance its
      transmission.

PMID- 16573692
TI  - Inorganic polyphosphate interacts with ribosomes and promotes translation
      fidelity in vitro and in vivo.
AB  - Inorganic polyphosphate is a biological macromolecule consisting of multiple
      phosphates linked by high-energy bonds. Polyphosphate occurs in cells from all
      domains of life, and is known to play roles in a diverse collection of cellular
      functions. Here we examine the relationship between polyphosphate and protein
      synthesis in Escherichia coli. We report that polyphosphate associates with E.
      coli ribosomes in vitro. Characterization of this interaction reveals that both
      long-chain and short-chain polyphosphates interact with the ribosome. Intact 70S
      ribosomes, as well as 50S and 30S subunits, display a specific interaction with
      polyphosphate that is mediated primarily by contacts with ribosomal proteins.
      Additionally, we examined functional consequences of a ppk mutation, which
      severely reduces levels of intracellular polyphosphate. Extracts from ppk mutants
      contain lower levels of polysomes than wild-type cells, suggesting a defect in
      mRNA utilization or the mRNA-ribosome interaction. Ribosomes from wild-type and
      ppk mutant cells were isolated, and their activities were compared using a polyU
      RNA in vitro translation assay. While rates of polyphenylalanine synthesis are
      similar, use of ribosomes from ppk cells results in a misincorporation rate about
      five times higher compared with the rate observed when ribosomes from wild-type
      cells are used. Mistranslation rates in vivo were measured directly, and ppk
      mutants displayed higher readthrough frequencies for two different stop codons.
      Taken together, these results indicate that polyphosphate plays an important role
      in maintaining optimal translation efficiency in vivo and in vitro.

PMID- 16573691
TI  - Bradyrhizobium japonicum senses iron through the status of haem to regulate iron
      homeostasis and metabolism.
AB  - The Irr protein from the bacterium Bradyrhizobium japonicum is expressed under
      iron limitation to mediate iron control of haem biosynthesis. The regulatory
      input to Irr is the status of haem and its precursors iron and protoporphyrin at
      the site of haem synthesis. Here, we show that Irr controls the expression of
      iron transport genes and many other iron-regulated genes not directly involved in
      haem synthesis. Irr is both a positive and negative effector of gene expression,
      and in at least some cases the control is direct. Loss of normal iron
      responsiveness of those genes in an irr mutant, as well as a lower total cellular
      iron content, suggests that Irr is required for the correct perception of the
      cellular iron status. Degradation of Irr in iron replete cells requires haem.
      Accordingly, control of Irr-regulated genes by iron was aberrant in a haem
      defective strain, and iron replete mutant cells behave as if they are iron
      limited. In addition, the haem mutant had an abnormally high cellular iron
      content. The findings indicate that B. japonicum senses iron via the status of
      haem biosynthesis in an Irr-dependent manner to regulate iron homeostasis and
      metabolism.

PMID- 16573693
TI  - The Escherichia coli plasma membrane contains two PHB (prohibitin homology)
      domain protein complexes of opposite orientations.
AB  - Two membrane proteases, FtsH and HtpX, are jointly essential for Escherichia coli
      cell viability, presumably through their abilities to degrade abnormal membrane
      proteins. To search for additional cellular factors involved in membrane protein
      quality control, we isolated multicopy suppressors that alleviated the growth
      defect of the ftsH/htpX dual disruption mutant. One of them was ybbK, which is
      renamed qmcA, encoding a membrane-bound prohibitin homology (PHB) domain family
      protein. Multicopy suppression was also observed with hflK-hflC, encoding another
      set of PHB domain membrane proteins, which had been known to form a complex
      (HflKC) and to interact with FtsH. Whereas the DeltaftsH sfhC21 (a viability
      defect suppressor for DeltaftsH) strain exhibited temperature sensitivity in the
      presence of cAMP, additional disruption of both qmcA and hflK-hflC exaggerated
      the growth defect. Pull-down and sedimentation experiments showed that QmcA, like
      HflKC, forms an oligomer and interacts with FtsH. Protease accessibility assays
      revealed that QmcA, unlike periplasmically exposed HflKC, possesses a
      cytoplasmically disposed large C-terminal domain, thus assuming the type I (NOUT
      CIN) orientation. We discuss possible significance of having PHB domains on both
      sides of the membrane.

PMID- 16573694
TI  - Characterization of the Staphylococcus aureus CidR regulon: elucidation of a
      novel role for acetoin metabolism in cell death and lysis.
AB  - The Staphylococcus aureus cid and lrg operons encode a novel regulatory system
      that affects murein hydrolase activity, stationary-phase survival and antibiotic
      tolerance. Expression of the lrgAB operon is positively regulated by a two
      component regulatory system encoded by the lytSR operon located immediately
      upstream to lrgAB. By comparison, the cidABC operon lies downstream from the cidR
      gene, encoding a protein homologous to the LysR-type family of transcriptional
      regulators. Transcription analysis of a cidR mutant revealed that CidR enhances
      cidABC expression in the presence of acetic acid generated by the metabolism of
      excess glucose. Microarray studies identified additional CidR-regulated operons
      including the IrgAB and alsSD encoding proteins involved in acetoin production.
      Surprisingly, Northern blot analyses revealed that cidABC and lrgAB transcription
      was uninducible in an alsSD mutant grown in the presence of excess glucose,
      suggesting that the CidR-mediated upregulation of cidABC and lrgAB transcription
      is dependent on the presence of intact alsSD genes. Zymographic and quantitative
      analyses of murein hydrolase activity also revealed that disruption of the alsSD
      genes results in significantly decreased extracellular murein hydrolase activity
      compared with that of the parental strain, UAMS-1. Furthermore, the alsSD mutant
      displayed decreased stationary-phase survival relative to UAMS-1, both in the
      presence and absence of glucose. The results of this study define the CidR
      regulon and demonstrate that the generation of acetoin is linked to the control
      of cell death and lysis in S. aureus.

PMID- 16573695
TI  - The carboxyl-terminal linker is important for chemoreceptor function.
AB  - Sensory adaptation in bacterial chemotaxis is mediated by chemoreceptor
      methylation and demethylation. In Escherichia coli, methyltransferase CheR and
      methylesterase CheB bind both substrate sites and a carboxyl-terminal
      pentapeptide sequence carried by certain receptors. Pentapeptide binding enhances
      enzyme action, an enhancement required for effective adaptation and chemotaxis.
      Pentapeptides are linked to the conserved body of chemoreceptors through a
      notably variable sequence of 30-35 residues. We created nested deletions from the
      distal end of this linker in chemoreceptor Tar. Chemotaxis was eliminated by
      deletion of 20-40 residues and reduced by shorter deletions. This did not reflect
      generalized disruption, because all but the most extremely truncated receptors
      activated kinase, were substrates for adaptational modification and performed
      transmembrane signalling. In contrast, linker truncations reduced rates of
      adaptational modification in parallel with chemotaxis. We concluded the linker is
      important for chemotaxis because of its role in adaptational modification.
      Effects of linker truncations on CheR binding to receptor-borne pentapeptide
      implied linker (i) makes pentapeptide available to modification enzymes by
      separation from the helical receptor body, and (ii) is a flexible arm allowing
      dual binding of enzyme to pentapeptide and modification site. The data suggest
      linker and the helix from which it emerges are structurally dynamic.

PMID- 16573696
TI  - Influences on gene expression in vivo by a Shine-Dalgarno sequence.
AB  - The Shine-Dalgarno (SD+: 5'-AAGGAGG-3') sequence anchors the mRNA by base pairing
      to the 16S rRNA in the small ribosomal subunit during translation initiation. We
      have here compared how an SD+ sequence influences gene expression, if located
      upstream or downstream of an initiation codon. The positive effect of an upstream
      SD+ is confirmed. A downstream SD+ gives decreased gene expression. This effect
      is also valid for appropriately modified natural Escherichia coli genes. If an
      SD+ is placed between two potential initiation codons, initiation takes place
      predominantly at the second start site. The first start site is activated if the
      distance between this site and the downstream SD+ is enlarged and/or if the
      second start site is weakened. Upstream initiation is eliminated if a stable stem
      loop structure is placed between this SD+ and the upstream start site. The
      results suggest that the two start sites compete for ribosomes that bind to an
      SD+ located between them. A minor positive contribution to upstream initiation
      resulting from 3' to 5' ribosomal diffusion along the mRNA is suggested. Analysis
      of the E. coli K12 genome suggests that the SD+ or SD-like sequences are
      systematically avoided in the early coding region suggesting an evolutionary
      significance.

PMID- 16573697
TI  - Evidence for the involvement of Plasmodium falciparum proteins in the formation
      of new permeability pathways in the erythrocyte membrane.
AB  - The intraerythrocytic developmental stages of the malaria parasite Plasmodium
      falciparum are responsible for the clinical symptoms associated with malaria
      tropica. The non-infected human erythrocyte is a terminally differentiated cell
      that is unable to synthesize proteins and lipids de novo, and it is incapable of
      importing a number of solutes that are essential for parasite proliferation.
      Approximately 12-15 h after invasion the parasitized cell undergoes a marked
      increase in its permeability to a variety of different solutes present in the
      extracellular milieu. The increase is due to the induction in the erythrocyte
      membrane of 'new permeability pathways' which have been characterized in some
      detail in terms of their transport and electrophysiological properties, but which
      are yet to be defined at a molecular level. Here we show that these pathways are
      resistant to trypsin but are abolished by treatment of intact infected
      erythrocytes with chymotrypsin. On resuspension of chymotrypsinized cells in
      chymotrypsin-free medium the pathways progressively reappear, a process that can
      be inhibited by cytotoxic agents, and by brefeldin A which inhibits protein
      secretion. Our results provide evidence for the involvement of parasite encoded
      proteins in the generation of the pathways, either as components of the pathways
      themselves or as auxiliary factors.

PMID- 16573698
TI  - Cloning, functional expression and characterization of Mesorhizobium loti
      arylamine N-acetyltransferases: rhizobial symbiosis supplies leguminous plants
      with the xenobiotic N-acetylation pathway.
AB  - Arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes
      involved in the detoxification of numerous aromatic chemicals. The NAT-dependent
      N-acetylation pathway has not previously been detected in plants. We demonstrate
      here the occurrence of the NAT-dependent pathway in leguminous plants, due to
      symbiosis with Mesorhizobium loti. We cloned two NAT enzymes from M. loti and
      showed that these two recombinant enzymes catalysed the N-acetylation of several
      known NAT substrates, including aniline-derived pesticide residues. We also
      demonstrate the existence of a functional NAT-dependent acetylation pathway in
      the root nodules of Lotus japonicus inoculated with M. loti. M. loti is the first
      non-eukaryotic organism shown to express two catalytically active NAT isoforms.
      This work also provides the first evidence for acquisition of a xenobiotic
      detoxification pathway by a plant through symbiosis with a soil microbe.

PMID- 16573699
TI  - Coactivation of Vibrio vulnificus putAP operon by cAMP receptor protein and PutR
      through cooperative binding to overlapping sites.
AB  - The cAMP receptor protein (CRP) positively regulates the expression of Vibrio
      vulnificus putAP genes encoding a proline dehydrogenase and a proline permease.
      In the present study, an open reading frame encoding PutR was identified
      downstream of the putAP genes and a mutational analysis revealed that the PutR
      protein was also involved in regulating the putAP transcription by activating
      Pput promoter. Although CRP acts as a primary activator and the influence of PutR
      on Pput is mediated by CRP, the level of Pput activity observed when PutR and CRP
      functioned together was greater than the sum of Pput activities achieved by each
      activator alone. Western blot analyses demonstrated that the cellular levels of
      PutR and CRP were not significantly affected by each other, indicating that PutR
      and CRP coactivate Pput rather than function sequentially in a regulatory
      cascade. Two adjacent binding sites for PutR mapped by in vitro DNase I
      protection assays were found to overlap the CRP binding sites and were centred 
      91.5 (PCBI) and -133.5 bp (PCBII) upstream of the transcription start site of
      Pput respectively. PutR and CRP bind to the sites cooperatively and a dissection
      of the role of the binding sites revealed that CRP at PCBI plays the most crucial
      role in the activation of Pput. Accordingly, the present results revealed that
      PutR and CRP coactivate the expression of Pput and exert their effect by
      cooperatively binding to the promoter.

PMID- 16573700
TI  - Four signalling domains in the hybrid histidine protein kinase RodK of Myxococcus
      xanthus are required for activity.
AB  - In prokaryotes, the principal signal transduction systems operating at the level
      of protein phosphorylation are the two-component systems. A number of hybrid
      histidine protein kinases in these systems contain several receiver domains,
      however, the function of these receiver domains is unknown. The RodK kinase in
      Myxococcus xanthus has an unconventional domain composition with a putative N
      terminal sensor domain followed by a histidine kinase domain and three receiver
      domains. RodK is essential for the spatial coupling of the two morphogenetic
      events underlying fruiting body formation in M. xanthus, aggregation of cells
      into nascent fruiting bodies and the subsequent sporulation of these cells. RodK
      kinase activity is indispensable for RodK activity. By systematically
      substituting the conserved, phosphorylatable aspartate residues in the three
      receiver domains, genetic evidence is provided that each receiver domain is
      important for RodK function and that each receiver domain has a distinct
      function, which depends on phosphorylation. Biochemical analyses provided
      indirect evidence for phosphotransfer from the RodK kinase domain to the third
      receiver domain. This is the first example of a hybrid histidine protein kinase
      in which four signalling domains have been shown to be required for full
      activity.

PMID- 16573702
TI  - Early pharmacological intervention in mild pediatric asthma--background and
      definitions.

PMID- 16573703
TI  - Early intervention of recent onset mild persistent asthma in children aged under
      11 yrs: the Steroid Treatment As Regular Therapy in early asthma (START) trial.
AB  - Inhaled corticosteroids are known to be effective in persistent asthma, but their
      long-term effect in mild persistent disease of recent onset, which is
      particularly relevant in children, requires clarification. The objective of this
      study was to determine the long-term efficacy of regular inhaled low-dose
      budesonide in children aged <11 yrs with mild persistent asthma with onset within
      2 yrs of enrollment. Children aged 5-10 yrs formed part of the population of the
      inhaled Steroid Treatment As Regular Therapy in early asthma (START) study, and
      they were randomized in a double-blind manner to treatment with once daily
      budesonide 200 microg or placebo via Turbuhaler in addition to usual clinical
      care and other asthma medication. The double-blind treatment phase continued for
      3 yrs. Of the 1974 children, 1000 in the budesonide group and 974 in the placebo
      group, were analyzed for efficacy. Addition of once-daily budesonide to usual
      care was associated with a significant increase in the time to first severe
      asthma-related event (SARE) and significantly reduced risk of SARE over 3 yrs.
      The hazard ratio relative to usual care (placebo) was 0.60 (95% confidence
      interval: 0.40-0.90; p = 0.012), with a relative risk reduction of 40%. Children
      receiving budesonide also needed significantly less intervention with other
      inhaled corticosteroids (12.3% vs. 22.5% over 3 yrs; p < 0.01), with trends
      towards decreased usage of oral/systemic corticosteroids and inhaled short-acting
      beta2-agonists. Budesonide treatment also had a significant beneficial effect on
      lung function relative to placebo. In conclusion, early intervention adding once
      daily budesonide to usual care in children with mild, persistent asthma of recent
      onset reduces the long-term risk and frequency of SAREs and improves lung
      function compared with usual care alone.

PMID- 16573705
TI  - Cost-effectiveness of early intervention with once-daily budesonide in children
      with mild persistent asthma: results from the START study.
AB  - The inhaled Steroid Treatment As Regular Therapy in early asthma (START) study
      has shown that early intervention with inhaled budesonide in mild persistent
      asthma improves clinical outcomes in both adults and children. The aim of this
      study was to estimate the incremental cost-effectiveness of early treatment with
      budesonide Turbuhaler in children aged 5-10 yr who participated in START. Direct
      and indirect costs associated with asthma were determined for 1974 children
      participating in the double-blind, 3-year part of the study. Randomization was to
      placebo or to budesonide 200 microg once daily in each case in addition to usual
      asthma care. Cost-effectiveness ratios were calculated from the healthcare
      payer's and societal perspectives (using US prices). The addition of once-daily
      budesonide therapy to usual asthma care was associated with 16 additional symptom
      free days (SFDs) per child over the 3-yr period (p < 0.001), with a substantial
      reduction (50%) in the mean number of days spent in hospital, and with reduced
      frequency of emergency room visits and missed school and caregiver work days.
      From the healthcare payer's perspective (direct costs), the increase in mean
      direct cost over 3 yr with budesonide was 169 dollars, which translated into an
      incremental cost of early intervention with budesonide in children of 10.50
      dollars (95% CI 1.20-33.30 dollars) per SFD gained. From the societal
      perspective, there was a cost reduction over 3 yr of 192 dollars with budesonide
      relative to placebo. From a societal perspective, budesonide was therefore
      dominant. In conclusion, early intervention with once-daily budesonide added to
      usual asthma care in children with mild persistent asthma is cost-saving from a
      societal perspective and is acceptably cost-effective when viewed from a
      healthcare payer perspective.

PMID- 16573704
TI  - Safety and tolerability of inhaled budesonide in children in the Steroid
      Treatment As Regular Therapy in early asthma (START) trial.
AB  - The safety and tolerability of asthma medications are still a concern to many
      asthma patients receiving long-term treatment. Therefore, more safety data from
      long-term, controlled trials are needed. The aim of this study was to evaluate
      the safety and tolerability of long-term treatment with once-daily budesonide in
      children aged 5-10 yrs with mild persistent asthma of recent onset in the inhaled
      Steroid Treatment As Regular Therapy in early asthma (START) study. Children aged
      5-10 yrs with early asthma were randomized to double-blind treatment with
      budesonide 200 microg or placebo once daily via Turbuhaler in addition to usual
      asthma therapy, for 3 yrs. Adverse events were recorded from both spontaneous
      reports and responses to standard questions, and asthma-related events and asthma
      control were recorded between visits and subsequently graded by the blinded
      investigators. Of the study population of 1981 children (1004 budesonide and 977
      usual care), 81% (812 of 1004) in the budesonide group and 82% (797 of 977) in
      the usual care group experienced a total of 6414 events listed by preferred term
      (3209 budesonide plus usual care and 3205 placebo plus usual care). The most
      commonly reported events included respiratory infection, pharyngitis, rhinitis,
      viral infection and bronchitis, and there were no clinically relevant differences
      in incidence between treatments. There were no reports of tuberculosis or
      aspergillosis, and no evidence of increased risk of systemic or ocular adverse
      events with budesonide relative to placebo. There were 106 serious adverse events
      in the budesonide group and 128 with usual care. The most frequent, aggravated
      asthma, was more common with usual care than with budesonide. There were no
      deaths among children participating in START. In conclusion, the addition of once
      daily inhaled budesonide 200 microg via Turbuhaler to usual care is safe and well
      tolerated in children with recent-onset mild persistent asthma.

PMID- 16573706
TI  - Effect of storage in short--and long-term commercial semen extenders on the
      motility, plasma membrane and chromatin integrity of boar spermatozoa.
AB  - For artificial insemination (AI) in pigs, preservation of liquid boar semen at 16
      20 degrees C is still common practice as sperm cryopreservation remains
      suboptimal in this species. To meet the different needs of the swine industry,
      several extenders have been developed to preserve semen in liquid form for short-
      and long-term storage. In the present study, three different commercial extenders
      devised for short-term (BTS+) or long-term preservation (MR-A and X-Cell), were
      used to test whether storage of semen from four mature, fertile boars at 17
      degrees C for 96 h would affect sperm characteristics relevant for fertility,
      such as motility, membrane integrity and chromatin stability. Computer-assisted
      sperm analysis, and stainings with the acylated membrane dye SYBR-14/propidium
      iodide, and acridine orange in connection with flow cytometry were used to
      evaluate these variables. Percentages of total motile spermatozoa decreased
      slightly, but significantly, after 72-96 h. While membrane integrity values
      varied during the period of study, no significant changes in either membrane
      integrity or chromatin stability were, however, registered. This suggests a
      customary 96-day storage at 17 degrees C in these extenders was too short an
      interval to cause losses of integrity in nuclear DNA in the boar population
      studied.

PMID- 16573707
TI  - Phosphodiesterase 5 inhibitors in the treatment of premature ejaculation.
AB  - To date, there is no FDA-approved therapy for premature ejaculation (PE).
      Recently, phosphodiesterase 5 inhibitors (PDE5-Is) have been demonstrated to have
      encouraging results in the treatment of PE by a few studies. The aim of this
      review was to assess the updated manuscripts and thereafter present the practical
      recommendations and possible mechanisms concerning PDE5-Is for treating PE. Using
      MEDLINE, we searched and assessed the peer manuscripts published from 1 January
      1996 to 1 September 2005 about PDE5-Is for treating PE. The results show that the
      number of patients in all the reports is very few and most of the studies do not
      employ double-blinded and placebo-controlled tests, though they are prospective
      and randomized. Therefore, the results and conclusions might be biased. PDE5-Is
      are suggested to be used in PE with old age or associated with erectile
      dysfunction (ED), or to be employed alone or in combination with selective
      serotonin reuptake inhibitors (SSRIs) when SSRIs fail to treat PE; behavioural
      therapy is proposed to be used for preventing the recurrence of PE following
      withdrawal of PDE5-Is. In addition, for the PE patient with a definite
      aetiological cause, the aetiology should be cured first, if PE still exists,
      followed by PDE-Is prescription. Possible mechanisms that are involved include
      relaxing the smooth muscles of vas deferens, seminal vesicle, prostate and
      urethra; decreasing the central sympathetic output; inducing peripheral
      analgesia; prolonging the duration of erection; and increasing confidence, the
      perception of ejaculatory control, overall sexual satisfaction, and decreasing
      the post-orgasmic refractory time to achieve a second erection after ejaculation.
      Well-designed multicentre studies are urgently warranted to further elucidate the
      efficacies and safety as well as mechanisms of PDE5-Is in the treatment of PE.

PMID- 16573708
TI  - A phase II randomized controlled trial of a novel male contraception, an intra
      vas device.
AB  - The aim of this study was to introduce a novel male contraceptive method, an
      intra-vas device (IVD), and to assess the efficacy, safety and satisfaction of
      recipients compared with no-scalpel vasectomy (NSV). A phase II randomized
      controlled trial was conducted in China in 2003. Two hundred and eighty-eight
      male subjects seeking vasectomy were randomly assigned to the IVD or NSV group.
      Follow up included a telephone questionnaire on the 14th postoperative day and
      visits at the third and 12th postoperative months. The follow-up rates at the
      three time points were 100%, 100% and 96.5% respectively. There was no technical
      failure in any subject. The surgical conditions were similar in both groups, but
      the IVD group experienced an additional 5 min of operative time (p<0.001). The
      IVD group recovered normal activity and sexual intercourse more rapidly (both
      p<0.05). The azoospermia rate was lower in the IVD group than in the NSV group at
      the third and 12th postoperative months. The rate of contraceptive success based
      on semen analyses was similar in both groups, especially at the 12th
      postoperative month (94.3% in the IVD group vs. 98.6% in the NSV group; p=0.054).
      The IVD group had less risk of complications (i.e. pain, congestive epididymitis
      and sperm granuloma). More subjects reported satisfaction with IVD sterilization
      than with NSV. The two procedures were similar in terms of surgical
      complications. The IVD was slightly less effective, but had a lower risk of later
      adverse events than the NSV technique. The IVD group also reported a higher level
      of satisfaction.

PMID- 16573709
TI  - A to G transitions at 260, 386 and 437 in DAZL gene are not associated with
      spermatogenic failure in Indian population.
AB  - The autosomal DAZL (Deleted-in-Azoospermic-Like) gene, mapped to the short arm of
      the human chromosome 3, is the precursor for the Y-chromosomal DAZ cluster, which
      encodes for putative RNA-binding proteins. Mutations in the DAZL have been
      reported to be associated with spermatogenic failure in Taiwanese population but
      not in Caucasians. As there was no study on Indian populations, we have analysed
      the entire coding sequences of exons 2 and 3 of DAZL in a total of 1010 men from
      Indian subcontinent, including 660 infertile men with 598 non-obstructive
      azoospermia, 62 severe oligozoospermia and 350 normozoospermic fertile control
      men, to investigate whether mutation(s) in the DAZL is associated with male
      infertility. Interestingly, none of our samples (1010) showed A386G (T54A)
      mutation, which was found to be associated with spermatogenic failure in
      Taiwanese population. In contrast, A260G (T12A) mutation was observed in both
      infertile and normozoospermic fertile control men, without any significant
      association with infertile groups (chi2= 0.342; p = 0.556). Similarly, we have
      found a novel A437G (I71V) mutation, which is also present in both infertile and
      normozoospermic fertile control men without any significant difference (chi2 =
      0.476; p = 0.490). Our study clearly demonstrates the complete absence of the
      A386G (T54A) mutation in Indian subcontinent and the other two mutations --A260G
      (T12A) and A437G (I71V)--observed are polymorpic. Therefore, we conclude that
      these mutations in the DAZL gene are not associated with male infertility in
      Indian subcontinent.

PMID- 16573710
TI  - Cardioprotection of cariporide evaluated by plasma myoglobin and troponin I in
      myocardial infarction in pigs.
AB  - The cardioprotective effects of cariporide were investigated against myoglobin
      and troponin I elevation in a model of myocardial infarction in pig, and the
      possible relationship between these markers and myocardial infarct size. The left
      circumflex coronary artery was ligated for 60-min and then reperfused for 48-h.
      Plasma levels of myoglobin and troponin I were quantified during reperfusion.
      Vehicle or cariporide (2.5 mg/kg) were administered i.v. before ischaemia and
      infused throughout ischaemia and for the beginning of reperfusion. In vehicle
      treated pigs, the infarct size represented 26% +/- 3% of the area at risk.
      Cariporide significantly decreased the infarct size by 66% +/- 9%, and
      significantly reduced plasma levels of myoglobin and troponin I. A strongly
      correlated linear relationship between myocardial necrosis and plasma levels of
      myoglobin (R = 0.966, P < 0.0001) or troponin I (R = 0.855, P < 0.0001) was
      clearly identified. In conclusion, in our porcine model of myocardial infarction,
      even with small infarcts (in the presence of cariporide), plasma levels of
      myoglobin and troponin I are predictive of the presence of necrosis and its
      extent.

PMID- 16573711
TI  - Nifedipine inhibits picrotoxin-induced seizure activity: further evidence on the
      involvement of L-type calcium channel blockers in epilepsy.
AB  - A large body of evidence supports the role of L-type calcium channels in
      epileptogenesis. The aim of the present study was to study the efficacy of the
      specific L-type calcium channel blocker nifedipine on seizure activity induced by
      picrotoxin (PTX). Adult female Sprague-Dawley rats were used in these
      experiments. The intraperitoneal administration of nifedipine (5 mg/kg) did not
      significantly alter the latency to onset of clonic seizure induced by
      intraperitoneal injection of PTX (4 mg/kg). Higher doses of the drug (10 and 20
      mg/kg) significantly increased the latency of onset of clonic seizure in a dose
      dependent manner. Nifedipine (10 mg/kg) did not reduce the incidence of clonic
      seizures in the animals injected with PTX, but inhibited tonic seizure and the
      progression of clonic seizures into maximal tonic seizures in four of eight of
      the animals. The drug (20 mg/kg) inhibited clonic seizure in four of six of the
      animals and abolished minimal or maximal tonic seizures in all the animals. In
      conclusion, our study provides further evidence on the antiepileptic effect of L
      type calcium channel blocker nifedipine by showing its protective effect on
      seizure activity induced by PTX.

PMID- 16573712
TI  - Effect of Spirulina, a blue green algae, on gentamicin-induced oxidative stress
      and renal dysfunction in rats.
AB  - Gentamicin (GM), an aminoglycoside, is widely employed in clinical practice for
      the treatment of serious Gram-negative infections. The clinical utility of GM is
      limited by the frequent incidence of acute renal failure. Experimental evidences
      suggest that oxidative and nitrosative stress play an important role in GM
      nephrotoxicity. Spirulina fusiformis is a blue green algae with potent free
      radical scavenging properties. The present study was designed to investigate
      renoprotective potential of S. fusiformis, against GM-induced oxidative stress
      and renal dysfunction. Spirulina fusiformis (500, 1000, 1500 mg/kg, p.o.) was
      administered 2 days before and 8 days concurrently with GM (100 mg/kg, i.p.).
      Renal injury was assessed by measuring serum creatinine, blood urea nitrogen and
      creatinine clearance and serum nitrite levels. Renal oxidative stress was
      determined by renal malondialdehyde levels, reduced glutathione levels and by
      enzymatic activity of superoxide dismutase (SOD) and catalase. Chronic GM
      administration resulted in marked renal oxidative and nitrosative stress and
      significantly deranged renal functions. Treatment with S. fusiformis
      significantly and dose-dependently restored renal functions, reduced lipid
      peroxidation and enhanced reduced glutathione levels, SOD and catalase
      activities. The results of present study clearly demonstrate the pivotal role of
      reactive oxygen species and their relation to renal dysfunction and point to the
      therapeutic potential of S. fusiformis in GM-induced nephrotoxicity.

PMID- 16573713
TI  - Effect of hyperleptinaemia on chronic ethanol-induced hepatotoxicity in mice.
AB  - Ethanol metabolism is accompanied by generation of free radicals, which stimulate
      lipid peroxidation. Previous studies have proposed a possible link between leptin
      and non-alcoholic fatty liver disease; however, the effect of leptin on ethanol
      induced liver diseases remains unclear. The aim of the present study was to
      explore the effect of leptin on ethanol-induced liver injury in mice.
      Administering ethanol (6.32 g/kg body weight p.o.) to 4-week-old healthy mice for
      45 days resulted in significantly elevated levels of plasma leptin, total
      bilirubin, gamma-glutamyl transpeptidase (GGT), tissue lipid hydroperoxides
      (LOOH), and lowered levels of tissue vitamins C and E when compared with those of
      the control mice. Subsequent to the experimental induction of hepatotoxicity
      (i.e. after the initial period of 30 days) exogenous leptin was administered (230
      microg/kg body weight i.p.) every alternate day for 15 days along with the daily
      dose of ethanol. Leptin administration to control and ethanol-treated mice
      significantly reduced the weight gain, elevated the plasma levels of leptin,
      bilirubin, GGT and tissue LOOH, and significantly lowered the levels of tissue
      vitamins C and E when compared with the untreated control and ethanol
      supplemented mice. It is postulated that the increase in systemic leptin levels
      enhances oxidative stress, and lowers antioxidant defence, leading to the
      augmented hepatic inflammation observed in alcoholic liver disease.

PMID- 16573714
TI  - Distribution of calcineurin activity in blood cell fractions and impact of
      tacrolimus inhibition.
AB  - The aim of this study was to investigate calcineurin (PP2B) activity in different
      blood cell fractions and its inhibition by tacrolimus. Basal PP2B activity was
      measured in each blood cellular fraction collected from healthy volunteers. The
      inhibition profile of PP2B activity was explored in isolated peripheral blood
      mononuclear cells (PBMC) and platelets exposed directly to tacrolimus and in PBMC
      and platelets isolated from whole blood previously exposed to tacrolimus.
      Contrasting with red blood cells (30%) and platelets (25%), PBMC represented only
      8.7% of PP2B activity of unfractionated whole blood. After tacrolimus exposure of
      isolated PBMC and platelets, the concentration of tacrolimus required to inhibit
      50% of PP2B activity (EC(50)) in PBMC was significantly lower than in platelets
      (0.26 ng/mL vs. 0.83 ng/mL, P < 0.001). EC(50) values were similar in PBMC and
      platelets isolated from whole blood previously exposed to tacrolimus (7.69 ng/mL
      vs. 7.42 ng/mL, respectively). These results suggest PBMC is a very suitable
      matrix for PP2B measurement in monitoring transplant recipients but clinical
      studies are necessary to solve clearly this issue.

PMID- 16573717
TI  - Anorexic dis(connection): managing anorexia as an illness and an identity.
AB  - This paper explores the ways in which young women 'manage' the complexities of
      the presentation of an anorexic identity, the stigma attached to it, and the
      relationships that are developed with fellow sufferers. A range of ethnographic
      data and 'voices' are drawn upon, including a small qualitative study within a
      leading centre in the UK for the treatment of eating disorders. The paper begins
      by outlining the ways in which for many young women, anorexia is a stigmatised
      identity which in various contexts comes to be perceived as an irrational and
      self-inflicted condition. It was reported by the young women in our study that
      many of their peers, families and teachers made sense of their eating disorder
      through a medicalised discourse which focused on visual aspects of weight
      gain/loss and often stigmatised the condition, reducing it to a position of
      pathology or irrationality. It is argued that these experiences form a type of
      'discursive constraint' (Ronai 1994) which many of the young women attempt to
      resist by engaging with alternative contexts and relationships through which they
      can construct more positive self-representations of anorexia or anorexic
      identities. As is revealed through the various data sources, as these young women
      negotiate the various discourses which offer them alternative subjectivities,
      they come to manage anorexia as both an illness and an identity.

PMID- 16573716
TI  - Constructing families and kinship through donor insemination.
AB  - This paper presents some central findings of an exploratory qualitative study of
      New Zealand families with children conceived by donor insemination (DI). Drawing
      on social anthropological and sociological theorising about kinship and
      contemporary Western families, the paper explores the ways in which parents and
      their kin actively construct parent-child relationships and kin connections
      through the notions of biological and social ties, nature and nurture. The paper
      discusses three major themes emerging from the data: the social construction of
      the 'natural facts' of procreation, physical resemblance, and the construction of
      families through choice, not biology. Whilst the primacy of biological or genetic
      connection is a powerful cultural theme, particularly evident in the ambiguities
      and uncertainties for social fathers and their kin, these families also
      deconstruct this notion. Drawing simultaneously on the power of social and
      biological connection, using biology as a metaphor for social relations, or by
      privileging social ties and the formation of families through choice, over time
      these families strategically establish themselves as the sole parents and kin of
      their children conceived by DI.

PMID- 16573718
TI  - 'Sex for life'? Men's counter-stories on 'erectile dysfunction', male sexuality
      and ageing.
AB  - Discourse on male sexuality in mid-to-later life has exploded in recent years
      (Gullette 1998). Attention to this topic has been spurred by the advent of
      (highly profitable) sexuopharmaceutical 'solutions' to erectile changes affecting
      older men. 'Success' stories abound in the media and in medical literature
      related to the restoration of faulty erections and ailing sex lives through drugs
      such as Viagra (sildenafil citrate), Uprima (apomorphine) and Cialis (tadalafil).
      In this paper we explore some of the ways in which notions about ageing and male
      sexuality are changing in popular cultural and medical texts in response to the
      advent of Viagra and the increasing authority of biomedicine in this area. We
      also demonstrate how the recent biomedical endorsement of 'sex for life' (the
      imperative to maintain an active youthful masculine [hetero]sexuality - defined
      in terms of male orgasm through penetrative sex) may be challenged by the very
      accounts of older men who are, or have been, affected by erectile difficulties
      and have used drugs like Viagra themselves. We present the perspectives of mid-to
      late life heterosexual men in New Zealand whose stories question the contemporary
      biomedical privileging of erections and intercourse 'at any cost and at any age'.
      We argue that the current push to identify and treat so-called erectile
      dysfunction (and restore erections and penetrative sex to relationships) neglects
      some men's own experiences of alternative modes of relating sexually that they
      identify as 'normal', 'healthy', 'enjoyable' and 'satisfying' for them and their
      partners; and undermines their understanding of such changes as positive outcomes
      of ageing, experience and maturity.

PMID- 16573719
TI  - The search for wellbeing in alternative and complementary health practices.
AB  - This article is premised on a need to understand and analyse how those turning to
      alternative and complementary medicines conceptualise the role of these
      practices; to ask what kind of 'health' is produced through alternative and
      complementary medicines and how might the help provided by these practices relate
      to questions of identity, self and subjectivity? Even though alternative and
      complementary medicines can be utilised in the face of serious illness, the
      healing produced through these practices is here argued to transcend
      physiological health and relate rather to a subjectively assessed sense of
      'wellbeing'. In this article, I analyse what this wellbeing entails, in
      particular, in terms of contemporary understandings of selfhood as well as in
      relation to the production of appropriate emotions through 'emotion management'.
      I argue that the wellbeing produced through alternative and complementary health
      practices can be conceptualised as a means of asserting a particular kind of self
      as well as a means of negotiating identities offered to people in wider societal
      discourses and institutions. This article is based on qualitative interviews with
      both practitioners and users of varied alternative and complementary medicines.
      The focus is on women's experiences.

PMID- 16573720
TI  - The politics of end-of-life decision-making: computerised decision-support tools,
      physicians' jurisdiction and morality.
AB  - With the increasing corporate and governmental rationalisation of medical care,
      the mandate of efficiency has caused many to fear that concern for the individual
      patient will be replaced with impersonal, rule-governed allocation of medical
      resources. Largely ignored is the role of moral principles in medical decision
      making. This analysis comes from an ethnographic study conducted from 1999-2001
      in three US Intensive Care Units, two of which were using the computerised
      decision-support tool, APACHE III (Acute Physiological and Chronic Health
      Evaluation III), which notably predicts the probability that a patient will die.
      It was found that the use of APACHE presents a paradox regarding concern for the
      individual patient. To maintain jurisdiction over the care of patients,
      physicians share the data with the payers and regulators of care to prove they
      are using resources effectively and efficiently, yet they use the system in
      conjunction with moral principles to justify treating each patient as unique.
      Thus, concern for the individual patient is not lessened with the use of this
      system. However, physicians do not share the data with patients or surrogate
      decision-makers because they fear they will be viewed as more interested in
      profits than patients.

PMID- 16573726
TI  - Therapeutic modulation of the psychoneuroimmune system by medical acupuncture
      creates enhanced feelings of well-being.
AB  - PURPOSE: This article includes an explanation of how stressors disrupt
      physiologic regulatory mechanisms leading to disease states, how environmental
      challenges alter the function of the psychoneuroimmune system, and how correction
      of aberrant action potentials will stabilize homeostatic regulatory functions,
      inducing an escape response from stressors and leading to enhanced feelings of
      well-being. An explanation of how medical acupuncture accomplishes this
      stabilization concludes the article. DATA SOURCE: Extensive review of the
      worldwide scientific literature from the 1970s through current literature, on
      acupuncture, neurophysiology, and psychoneuroimmune system, using the theoretical
      framework of Martha Rogers. CONCLUSIONS: It is estimated that 80% of all
      illnesses are stress induced, although the physiologic mechanisms by which stress
      induces detrimental changes are not well understood by the medical profession.
      Introducing specific rhythmic electrical impulses slightly more intense than the
      nervous system already generates with the intervention of medical acupuncture can
      therapeutically alter aberrant signals induced by stressors, which may result in
      the release of neuropeptides and stabilization of homeostatic regulation so that
      health outcomes are improved. As neurological activity is altered, the firing
      pattern of nerves is changed. This is a change in the electrical pattern that
      leads to a change in the biochemical pattern. Thus, medical acupuncture is a
      therapy that is in agreement with Martha Rogers' conceptual model. Therapeutic
      techniques may improve the individual's level of wellness by direct actions
      toward homeostatic stabilization of the autonomic nervous system. These
      techniques will not change the amount of stressors a person is subject to but
      will change the physiological response to them. When the nervous system is in
      homeostatic balance, individuals will report enhanced feelings of well-being, be
      more effective in coping with their conditions of living, and therefore be less
      susceptible to illness. IMPLICATIONS FOR PRACTICE: Nurse practitioners have an
      opportunity to expand into an unused dimension for nursing care through direct
      treatment of the central and autonomic nervous system that will influence the
      psychoneuroimmune system. A prescriptive theory explaining medical acupuncture
      provides for therapeutic interventions at the primary, secondary, and tertiary
      level of care. Primary preventive interventions alter the effects of stress
      before it leads to illness by assisting homeostatic stability of the autonomic
      nervous system. Secondary interventions allow treatment of many health conditions
      regulated by neurological activity. Tertiary care provides a method to assist
      autonomic regulation when the body is no longer able to maintain homeostatic
      stability because of chronic illness or injury.

PMID- 16573727
TI  - Primary care health issues among men who have sex with men.
AB  - PURPOSE: The purpose of the article is to examine "appropriate" health care for
      men who have sex with men (MSM), which is not to suggest "special" health care.
      As a group, MSM are at increased risk for sexually transmitted infections, anal
      cancer, and mental health disorders. Focus areas in this article will address
      health issues that the primary care nurse practitioner (NP) may encounter in
      clinical practice: anal carcinoma, sexually transmitted diseases (STDs), high
      risk sexual practices, depression, and substance abuse were topics chosen for
      inclusion in this article. These topics were among those highlighted in the
      Healthy People 2010 Companion Document for LGBT Health, which served to examine
      the healthcare disparities and lack of access to needed services related to
      sexual orientation. DATA SOURCE: Extensive literature review of research
      articles, journals, clinical practice guidelines, books, and public health
      department Internet Web sites. CONCLUSIONS: There are unique health disparities
      that exist for MSM related to social, emotional, and mental health factors, in
      addition to physical issues such as STDs. There is an increasing need for primary
      care providers to be aware of these disparities, as well as the factors that
      influence these disparities, in order to provide multidimensional care and health
      counseling that is unique to NP practice. IMPLICATIONS FOR PRACTICE: Both the
      primary care NP and the patient should be aware of the unique healthcare issues
      among MSM that should be incorporated into the patient's routine health
      maintenance program. As primary care providers, it is within the standards of
      practice for NPs to provide culturally competent care, along with health
      promotion and disease prevention for MSM.

PMID- 16573728
TI  - The influences of postdischarge management by nurse practitioners on hospital
      readmission for heart failure.
AB  - PURPOSE: The primary purpose of this literature review is to examine advanced
      practice nurse (APN)-directed versus registered nurse (RN)-directed
      telemanagement programs for heart failure patients. DATA SOURCES: Research
      articles identified through CINAHL and OVID databases. CONCLUSIONS: Implementing
      a telemanagement program directed by an APN after hospital discharge decreases
      the costs and frequent rehospitalizations associated with heart failure and
      improves the patient's quality of life. While APNs are more costly than RNs, it
      is important to understand that this level of provider has a more significant
      impact on the outcomes of patients who use the services provided in the
      comprehensive discharge programs. IMPLICATIONS FOR PRACTICE: An APN-directed
      heart failure telemanagement program can reduce the rising healthcare costs that
      result from frequent readmissions. These programs can improve the quality of care
      given to heart failure patients while reducing the cost to the institution, the
      patient, and the healthcare system. When considering the number of older adults
      hospitalized each year with heart failure, the potential patient benefits and
      savings to the healthcare system resulting from APN-directed telemanagement are
      substantial.

PMID- 16573729
TI  - Emergency contraception: knowledge and perceptions in a university population.
AB  - PURPOSE: The purpose of this study was to examine knowledge, attitudes, and
      behaviors regarding emergency contraception (EC) in university men and women aged
      18-21. DATA SOURCES: Data sources included responses to a 25-item questionnaire
      and an 8-item demographic survey completed anonymously at a public site on
      campus. Ninety-seven university students participated in the study. Participants
      were asked to respond to questions relating to knowledge, attitudes, and
      behaviors regarding EC, perceived worthiness, objections, sources of information
      about EC, preferred birth-control method and usage, and perceptions of their
      personal risk of unintended pregnancy. CONCLUSIONS: Many respondents considered
      unintended pregnancy to be a major problem and considered EC a worthy option in
      the event of method failure or unprotected intercourse. While most participants
      were aware that there was a postcoital method of contraception, confusion existed
      between EC and RU-486 (the abortion pill). Almost half (49.5%) believed that EC
      was the same as RU-486. There was an association between advanced prescription
      for EC and its likelihood of use. Most women would be significantly more likely
      to use EC if they had a prescription on hand. Of the women who were less likely
      to choose EC, 100% indicated they would feel embarrassed or judged when asking
      for it. Only 34% of those women who have had a gynecological exam in the past 12
      months had discussed EC with their provider. IMPLICATIONS FOR PRACTICE: Advanced
      practice nurses need to incorporate EC into preventive health counseling for both
      men and women. Providing women with an advanced prescription increases the
      likelihood that women will use EC.

PMID- 16573730
TI  - Tobacco prevention in children and cessation in family members.
AB  - PURPOSE: To examine the effects of a theory-driven tobacco prevention program in
      sixth-grade children with a family tobacco cessation component implemented by
      school nurses in conjunction with the initiation of a statewide toll-free Quit
      Line. DATA SOURCES: Self-report questionnaires completed by the sixth-grade
      children and their parents/guardians (N= 1024) representing largely rural
      southern school systems from disparate areas with high prevalence rates of
      tobacco use and lung cancer diagnoses. Pre- and posttest measures that evaluated
      the impact of both student and parent/guardian interventions were obtained over a
      10-week period. Paired t-tests were used to examine differences between pre- and
      posttest scores for all student and parent/guardian variables. Repeated-measures
      analysis of variance was used to examine the effect of parent/guardian smoking on
      student pre- and posttest scores. CONCLUSIONS: The student program resulted in
      significant improvements in drug knowledge, refusal skills, attitudes, normative
      expectations, assertiveness, and anxiety reduction techniques. In addition, the
      effectiveness of several components of the tobacco prevention program for the
      children was impacted by the smoking status of their parents/guardians. Drug-use
      intentions and behaviors were lower at posttest for children from homes of
      nonsmokers versus children from homes of smokers. Parents/guardians consistently
      reported that smoking was detrimental to themselves, the public, and their
      children. Of those parents/guardians who identified themselves as smokers (26%)
      and received cessation materials, 46.4% indicated that the information motivated
      them to want to quit. IMPLICATIONS FOR PRACTICE: Tobacco use continues to be the
      leading cause of preventable death in the United States, with greater than 2000
      new youth becoming regular smokers each day. School nurses and nurse
      practitioners are in various pivotal positions to address tobacco and its related
      health concerns through delivery of effective family interventions that target
      children for tobacco prevention and parent/guardian smokers for cessation.

PMID- 16573732
TI  - Digestive tract ontogeny of Dicentrarchus labrax: implication in osmoregulation.
AB  - The ontogeny of the digestive tract (DT) and of Na(+)/K(+)-ATPase localization
      was investigated during the early postembryonic development (from yolk sac larva
      to juvenile) of the euryhaline teleost Dicentrarchus labrax reared at two
      salinities: seawater and diluted seawater. Histology, electron microscopy and
      immunocytochemistry were used to determine the presence and differentiation of
      ion transporting cells. At hatching, the DT is an undifferentiated straight tube
      over the yolk sac. At the mouth opening (day 5), it comprises six segments:
      buccopharynx, esophagus, stomach, anterior intestine, posterior intestine and
      rectum, well differentiated at the juvenile stage (day 72). The enterocytes
      displayed ultrastructural features similar to those of mitochondria-rich cells
      known to be involved in active ion transport. At hatching, ion transporting cells
      lining the intestine and the rectum exhibited a Na(+)/K(+)-ATPase activity which
      increased mainly after the larva/juvenile (20 mm) metamorphic transition. The
      immunofluorescence intensity was dependent upon the stage of development of the
      gut as well as on the histological configuration of the analyzed segment. The
      appearance and distribution of enteric ionocytes and the implication of the DT in
      osmoregulation are discussed.

PMID- 16573731
TI  - Promoting nurse practitioner practice through research: opportunities,
      challenges, and lessons.
AB  - PURPOSE: To discuss the opportunities derived, challenges faced, and lessons
      learned in the research process, including recruiting and retaining nurse
      practitioner (NP) participants, obtaining institutional approval, and solving
      research team issues in a National Institutes of Health/National Institute of
      Nursing Research (NIH/NINR)-funded study of communication between NPs and their
      older patients in managed care and non-managed care settings. DATA SOURCES: The
      video-taped interactions between 30 NPs and 150 patients, research team
      experiences in conducting the research, and a review of relevant literature.
      CONCLUSIONS: Key factors in NP study participation included recognizing the
      importance of research in demonstrating the effectiveness of the NP role and for
      advancing the profession, having participated in previous research, enjoying the
      research process, employer incentives, membership in NP professional
      organizations, relationships with the university and the school of nursing
      conducting the research, and knowledge of the coinvestigator's work. NP
      recruitment was facilitated by word of mouth, professional organization
      assistance, and articles in a widely distributed, free nursing journal. Data
      collection was significantly delayed by attrition of NP participants, logistical
      problems with scheduling and travel, and varied approval procedures by
      Institutional Review Boards (IRBs) at study sites. The pace of nursing research
      could be much more efficient if IRB processes involved fewer bureaucratic
      entanglements. Preliminary study findings, however, show positive outcomes for
      older patients after NP care. IMPLICATIONS FOR PRACTICE: To demonstrate positive
      patient outcomes and move the NP profession forward, NPs must be willing to
      commit to participation in research on their effectiveness as providers in
      today's healthcare environment.

PMID- 16573733
TI  - Transgenic analysis of the medaka mesp-b enhancer in somitogenesis.
AB  - Somitogenesis is a critical step during the formation of metameric structures in
      vertebrates. Recent studies in mouse, chick, zebrafish and Xenopus have revealed
      that several factors, such as T-box genes, Notch/Delta, Wnt, retinoic acid and
      FGF signaling, are involved in the specification of nascent somites. By
      interacting with these pathways, the Mesp2-like bHLH transcription factors are
      transiently expressed in the anterior presomitic mesoderm and play a crucial role
      in somite formation. The regulatory mechanisms of Mesp2 and its related genes
      during somitogenesis have been studied in mouse and Xenopus. However, the precise
      mechanism that regulates the transcriptional activity of Mesp2 has yet to be
      determined. In our current report, we identify the essential enhancer element of
      medaka mesp-b, an orthologue of mouse Mesp2, using transgenic techniques and
      embryo manipulation. Our results demonstrate that a region of approximately 2.8
      kb, upstream of the mesp-b gene, is responsible for both the initiation and
      anterior localization of mesp-b transcription within a somite primordium.
      Furthermore, putative motifs for both T-box transcription factors and Notch/Delta
      signaling are present in this enhancer region and are essential for activity.

PMID- 16573734
TI  - Rap-GEF/Rap signaling restricts the formation of supernumerary spermathecae in
      Drosophila melanogaster.
AB  - Sperm storage in the female is a key factor for reproductive success in a variety
      of organisms, including Drosophila melanogaster. The spermathecae (SP) are the
      Drosophila organs for long-term storage. While wild-type female flies have two
      SP, occasionally, three or four SP have been observed in mutant flies. However,
      the molecular mechanism of SP formation is unknown. Here we show that loss of
      function of a Drosophila Rap-GEF (GEF26) result in an occurrence of the
      supernumerary SP; females have three SP (varies from 11 to 62% in different
      allele combinations) instead of the normal two SP. In addition, the Gef26 mutant
      flies also have ectopic wing veins and extra mechanosensory organs. The
      supernumerary SP phenotype of the Gef26 mutation can be enhanced by the
      Drosophila Rap mutations and rescued by overexpressing the cell adhesion molecule
      DE-cadherin. These data suggest that the Rap-GEF/Rap signaling controls the
      formation of supernumerary spermathecae through modulating cell adhesion in
      Drosophila.

PMID- 16573735
TI  - Peroxisome proliferator-activated receptor gamma ligands stimulate myeloid
      differentiation and lipogenensis in human leukemia NB4 cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a central role
      in adipocyte and macrophage differentiation. Pioglitazone (Actos, AD4833), an
      antidiabetic drug, and 15-deoxy-Delta(12,14)-prostaglandin J2 (PGJ2) have
      recently been identified as synthetic and natural ligands for PPARgamma,
      respectively. In this study, we examined the effects of PPARgamma ligands on
      differentiation and lipogenesis in promyelocytic leukemia NB4 cells, in which
      PPARgamma protein was expressed and ligand-stimulated PPARgamma-specific
      transcription of adipocyte fatty-acid binding protein was confirmed. Treatment
      with PPARgamma ligand (AD4833 or PGJ2) alone markedly suppressed proliferation
      but did not induce differentiation. The combined treatment of the cells with
      PPARgamma ligand and all-trans retinoic acid (ATRA) synergistically induced
      myelocytic differentiation, as determined by nitroblue tetrazolium reducing
      ability and cell morphology. During these processes of differentiation, we
      observed marked accumulation of lipid droplets in the cytoplasm. The cellular
      triacylglycerol levels increased 2.7-fold after treatment with the inducers.
      Simultaneously, BODIPY-fatty acid was incorporated into the cytosol and
      concentrated in lipid droplets. The biosynthesis of triacylglycerol-containing
      BODIPY-fatty acids was increased twofold in differentiated cells. These findings
      clearly demonstrate that treatment with PPARgamma ligands not only induced
      differentiation but also stimulated lipogenesis in NB4 cells, indicating a close
      association between differentiation and lipogenesis in PPARgamma-stimulated human
      myeloid cells.

PMID- 16573736
TI  - Programmed cell death of follicular epithelium during the late developmental
      stages of oogenesis in the fruit flies Bactrocera oleae and Ceratitis capitata
      (Diptera, Tephritidae) is mediated by autophagy.
AB  - In the present study, we describe the features of programmed cell death of
      ovarian follicle cells, occurring during the late developmental stages of
      oogenesis in the olive fruit fly, Bactrocera oleae and the medfly, Ceratitis
      capitata. During stage 14, the follicle cells contain autophagic vacuoles, and
      they do not exhibit caspase activity in all parts of the egg chamber. Their
      nuclei are characterized by condensed chromatin, accompanied with high- but not
      low-molecular weight DNA fragmentation events exclusively detected in distinct
      cells of the anterior pole. These data argue for the presence of an autophagy
      mediated cell death program in the ovarian follicle cell layer in both species.
      The above results are likely associated with the abundant phagocytosis observed
      at the entry of the lateral oviducts, where numerous cell bodies are massively
      engulfed by epithelial cells. We strongly believe that during the termination of
      the above Dipteran oogenesis, an efficient mechanism of absorption of the
      degenerated follicle cells is selectively activated, in order to prevent the
      blockage of the ovarioles and thus robustly support the physiological completion
      of the ovulation process.

PMID- 16573737
TI  - Small GTPase RacF2 affects sexual cell fusion and asexual development in
      Dictyostelium discoideum through the regulation of cell adhesion.
AB  - Cells of Dictyostelium discoideum become sexually mature when submerged and in
      darkness, and fuse with opposite mating-type cells as gametes. The gene for a Rho
      GTPase, RacF2, is one of the extremely gamete-enriched genes (>100-fold)
      identified by us previously. Here, we isolated knockout, overexpression,
      constitutively active and dominant negative mutants of RacF2, and analyzed their
      phenotypes. These mutants showed anomalies in the extent of sexual cell fusion
      and asexual development as well as in EDTA-sensitive cell-cell adhesion. It is
      suggested that RacF2 controls the process of sexual and asexual development
      through the regulation of cellular adhesiveness. An analysis of the expression of
      all 18 rac family genes by real-time polymerase chain reaction revealed that four
      additional genes, rac1b, rac1c, racF1 and racG, were induced during maturation,
      suggesting their possible involvement in sexual cell interactions.

PMID- 16573739
TI  - Response to splenectomy is durable after a certain point in time in adult
      patients with chronic immune thrombocytopenic purpura.
AB  - Splenectomy may lead to a good response in 60-80% of adult patients with
      corticosteroid refractory idiopathic thrombocytopenic purpura (ITP) but, the long
      term response to splenectomy still remains less well defined. We assessed the
      long-term efficacy and safety of splenectomy in adult patients with chronic ITP.
      A cohort of 59 splenectomised ITP patients (M/F = 25/34; median age 39 yr; range
      14-75) were followed up for a median of 18 yr (range 2-32). No life-threatening
      surgical complications were observed. The overall response rate was 78% with 59%
      complete remission (CR) and 19% partial remission (PR). CR and PR patients were
      younger than non-responding patients at time of diagnosis (median age: 36 yr vs
      48 yr, P = 0.03) and at splenectomy (median age: 38 yr vs 51 yr, P = 0.02). Among
      the 46 responding patients, eventually 17 had relapse. No disease progression
      occurred after 12.1 and 7.3 yr for patients in CR or PR, respectively. One case
      of fatal septicaemia was recorded. We conclude that splenectomy is an effective
      and safe treatment in adult patients with chronic ITP failing to respond to
      corticosteroid treatment and importantly, our findings support the view that
      response to splenectomy is durable after a certain point in time.

PMID- 16573738
TI  - Time-lapse analysis reveals different modes of primordial germ cell migration in
      the medaka Oryzias latipes.
AB  - Previous studies have shown that medaka primordial germ cells (PGC) are first
      distinguishable by olvas expression during late gastrulation, and that they
      migrate to the gonadal region through the lateral plate mesoderm. Here, we
      demonstrate that medaka nanos expression marks the germ line at early
      gastrulation stage. By marking the germ line with green fluorescent protein (GFP)
      fused to the nanos 3' untranslated region, we were able to visualize the behavior
      of PGC using time-lapse imaging. We show that there are three distinct modes of
      PGC migration that function at different stages of development. At early
      gastrulation stage, PGC actively migrate towards the marginal zone, a process
      that requires the function of a chemokine receptor, CXCR4. However, at late
      gastrulation stage, PGC change the mode and direction of their movement, as they
      are carried towards the midline along with somatic cells undergoing convergent
      movements. After aligning bilaterally, PGC actively migrate to the posterior end
      of the lateral plate mesoderm. This posterior movement depends on the activity of
      both HMGCoAR and a ligand of CXCR4, SDF-1a. These results demonstrate that PGC
      undergo different modes of migration to reach the prospective gonadal region of
      the embryo.

PMID- 16573740
TI  - Absence of hot spot mutations of the PIK3CA gene in acute myeloid leukaemia.

PMID- 16573741
TI  - Frequency of RAS gene mutation and its cooperative genetic events in Southeast
      Asian adult acute myeloid leukemia.
AB  - RAS gene as one of the most frequently mutated genes in acute myeloid leukemia
      (AML) has become an attractive target for molecular therapy. The role of
      oncogenic RAS and its associated genetic events in AML are not yet defined. We
      examined the frequency of RAS mutation in 239 Thai de novo adult AML patients
      using polymerase chain reaction-single-strand conformational polymorphism
      analysis. Thirty-five RAS mutations were found in 32 cases (13%) predominantly
      classified as M1/M2 (53%) followed by M4/M5 subtype (38%). Ten cases were
      positive for N-RAS codon 12, 11 cases for N-RAS codon 61, 13 cases for N-RAS
      codon 13, and one case for K-RAS codon 13. No mutation was found in K-RAS exon 2
      or H-RAS. The most common base substitution was the G to A transition at codon
      13. Most M1/M2 cases had mutations at codon 12 or 13, whereas M4/M5 cases
      preferentially affected codon 61. Half of the patients with RAS mutations had
      abnormal karyotypes with the majority involving chromosomes 21, 11 and 7. Four
      patients had core-binding factor leukemia and four additional patients had
      coexisting FLT3 or AML1 mutation. One patient had RAS, FLT3 and t(8;21) and the
      other had RAS, AML1 point mutation and del(9q). In conclusion, mutation of RAS
      gene was not as common in the Thais as in the western population. Several
      additional genetic abnormalities occurred in RAS-mutated patients. Future
      molecular-targeting approaches should take into account the multiple genetic
      events that coexist with RAS mutations in AML patients.

PMID- 16573742
TI  - Prospective study of 174 de novo acute myelogenous leukemias according to the WHO
      classification: subtypes, cytogenetic features and FLT3 mutations.
AB  - We report a prospective study of 174 unselected adult de novo acute myeloid
      leukemia (AML) cases diagnosed using the WHO classification. Of those, 57 (33%)
      were AML with recurrent cytogenetic abnormalities, 41 were (24%) AML with
      multilineage dysplasia, 74 (42%) were AML not otherwise categorized, and two were
      acute leukemias of ambiguous lineage. Clonal cytogenetic abnormalities were
      detected in 64% of the WHO AML cases with t(15;17) (15%), t(8;21) (12%), +8
      (11%), -7/del7q (8%) and del9q (5%) being the most common ones. The FLT3/ITD
      mutations (FMS-like tyrosine kinase 3/internal tandem duplication) were observed
      in 12% of the WHO AML cases, which is much lower than ones in the literature,
      while the 6% incidence of the FLT3-activating loop mutations (either FLT3/D835 or
      FLT3/I836) was comparable with others. Both mutations were associated with
      leukocytosis. Our study also suggests that the FLT3 mutations are biomarkers
      independent of cytogenetic characteristics.

PMID- 16573745
TI  - Absence of veno-occlussive disease in a cohort of multiple myeloma patients
      undergoing autologous stem cell transplantation with targeted busulfan dosage.
AB  - BACKGROUND: Plasma concentrations of oral busulfan (BU) were measured in multiple
      myeloma (MM) patients undergoing autologous peripheral blood stem cell
      transplantation (ASCT) with a double alkylating conditioning protocol in order to
      individualise doses of BU based on individual pharmacokinetic parameters and to
      reduce toxicities related to BU exposure. PATIENTS AND METHODS: Forty-four
      consecutive patients with MM participating in the co-operative Spanish protocol
      were prospectively evaluated. Conditioning regimen prior to autologous infusion
      consisted of BU followed by melphalan. BU pharmacokinetic parameters were
      estimated for each patient after the first dose based on measured concentrations
      and subsequent doses were modified as necessary to achieve target exposure.
      RESULTS: Mean BU exposure (AUCss) (+/-DS) before dosage modification range from
      3192 to 12 180 ng h/mL. Twenty-six out of 44 (59%) patients required dose
      adjustment. None of the patients developed hepatic veno-occlusive disease (VOD).
      Grade > or = II oropharyngeal mucositis was observed in the majority of patients
      (95%) and the severity of mucositis increased with increasing average steady
      state BU plasma concentration. There were four treatment-related deaths: two
      patients died from multiorgan failure and two of respiratory infections. Of the
      remaining 40 patients, 15 were in complete remission with negative
      immunofixation, 21 in partial remission and four in stable disease 3 months after
      ASCT. CONCLUSIONS: The results of the present study show the variability in BU
      pharmacokinetic parameters and suggest the possible relationship between
      toxicities and BU exposure. Individualising BU dosage in MM patients undergoing
      ASCT we observed the absence of VOD.

PMID- 16573746
TI  - Through the Iron Curtain: analytical space in post-Soviet Russia.
AB  - This paper discusses the experience of working as an analyst in post-totalitarian
      Russia in order to explore some of the general theoretical and clinical issues
      involved in working in a different cultural and linguistic context, and the
      particular problems encountered in the Russian cultural context. It describes how
      the Soviet regime worked actively to create a new totally collective mentality
      through the destruction of individual differences and the collectivization of
      private space, and the effects this produced in the individual and collective
      psyche. It examines the difficulties encountered when working with Russian
      analysands in creating and maintaining the setting, in preserving boundaries, in
      creating analytical space, and in working with certain particular transference
      countertransference dynamics. It focuses on the contrast between my own Western
      experience of space and the spatial experience of the analysands, and describes
      the process of helping them use analytical space to interiorize and create a new
      experience of psychic space. The paper uses dreams to illustrate some of these
      dynamics, and the particular psychic problems associated with the traumas created
      by totalitarian regimes.

PMID- 16573743
TI  - Cord blood transplantation for acute myelogenous leukemia using a conditioning
      regimen consisting of granulocyte colony-stimulating factor-combined high-dose
      cytarabine, fludarabine, and total body irradiation.
AB  - The cytotoxic effect of cytarabine (Ara-C) on myeloid leukemic cells is enhanced
      by concomitant use of granulocyte colony-stimulating factor (G-CSF) in vitro. The
      feasibility of a conditioning regimen consisting of G-CSF-combined 24 g/m2 Ara-C,
      90 mg/m2 fludarabine, and 12 Gy total body irradiation was studied for five
      patients with acute myelogenous leukemia in cord blood transplantation (CBT).
      Graft vs. host disease (GVHD) prophylaxis consisted of cyclosporine and
      methotrexate. After the conditioning regimen, 2.48 x 10(7)/kg (2.28-3.53) of cord
      blood nucleated cells was infused. Neutrophil counts consistently >0.5 x 10(9)/L
      was achieved 24 d (22-32) after CBT. Grade I stomatitis and gastrointestinal
      toxicities occurred in all patients. Grades I and II acute GVHD occurred in one
      and four patients, respectively, which resolved without steroid therapy. Sepsis
      and aspergillosis occurred in two and one patients, respectively. All patients
      were alive without leukemia relapse at a follow up of 15 months (12-43) after
      CBT. This conditioning regimen could avoid the toxicities of high-dose
      cyclophosphamide but might enhance the cytotoxic effect of Ara-C. Large-scale
      studies will be needed to determine the efficacy and safety of the conditioning
      regimen in CBT.

PMID- 16573748
TI  - The art of the tincture: analytical supervision.
AB  - Using the alchemical metaphor, effective supervision can be seen as an excellent
      example of the tincture: a little goes a long way. This paper offers a model of
      the dynamics in analytical supervision: a mirroring of the professional-self of
      the supervisee, the opportunity to learn through empirical factual knowledge,
      and, most importantly, experiential, interactive and dynamic learning. The
      container of supervision will be amplified using an image of the triple vessel of
      alchemy. The materia of supervision is discussed as 'amalgams' of complex related
      material. The supervisory field is seen in a triadic intersubjective and
      interimaginal manner. Jung's diagram of all the possible conscious and
      unconscious connections between patient and therapist is expanded to include the
      supervisory situation. Moving beyond projective identification as explanatory
      process, the concept of the mundus imaginalis is used as the medium for this
      triadic structure. The 'analytic third' expands to include the 'supervisory
      fourth' while incorporating the supervisor's imaginings of the patient as the
      quintessential experience of the imaginal other. The supervisor's attitude and
      state of mind are seen through the paradigm of active imagination. This state of
      mind is called supervisory reverie.

PMID- 16573747
TI  - 'Held in mind' or 'Hell in mind': group therapy in Poland.
AB  - This paper describes observations and experiences gathered whilst conducting
      group therapy with trainees in analytical psychology in Poland. The challenges
      and conflicts around language and translation reflect challenges common to
      analysis everywhere: accuracy of interpretation, agreements on permission to
      interpret and the acceptability of interpretation. The way in which archetypal
      patterns developed and matured suggests this approach to work with trainees may
      have wider application.

PMID- 16573749
TI  - Fifty years on: a training for the 21 century, from couple to community.
AB  - The paper describes the gradual transformation of the structures, process and
      content of the adult training at the Society of Analytical Psychology (SAP) from
      1997 when the potential for individuation had gone awry through lack of a
      culturally relevant and coherent programme until 2005 when trainees' professional
      and personal individuation could be enhanced by a process and a curriculum
      representing fairly the interests and beliefs of the range of different
      approaches to Jungian psychology that are to be found in the SAP. The process has
      taken eight years to complete and in the paper, the authors, two successive
      Directors of Training, describe the persistent resistances to necessary change
      from within their Society, focusing in particular on the key role of the founder
      member; the privileging of the internal world at the expense of significant
      external factors; a confusion of roles among members between volunteers and
      professionals and last, but by no means least, the contamination of the educative
      task and the creation of a training community by fantasies of the mother/infant
      couple.

PMID- 16573750
TI  - Who's afraid of the Wolfe couple: the interlocking traumatic scene.
AB  - Fulfilling intimate relationships require a constant emotional and psychological
      struggle to disentangle strangleholds created by the interpenetration of
      unresolved complexes stemming from previous disappointing relational experiences.
      These complexes may manifest as an encrypted pattern of engagement that each
      partner brings to the marriage, like a 'malignant dowry'. The dowry box, once
      opened, releases its nefarious contents to create an extremely complex and
      entangled drama I call the 'interlocking traumatic scene'. Partners unconsciously
      entrap each other to play a part in such a scene with double (sometimes multiple)
      roles for each antagonist. The imaginal space between the two characters can be
      seen as a projection screen, upon which are superimposed two separate shadow
      plays, one on each side of the screen. A third play, which is a co-created
      product of these two individual traumatic scenes, can also be observed. Three
      plays are performed simultaneously. The defensive systems that the two
      individuals bring to the equation dovetail together, but the actual interlocking
      mechanism itself deadlocks in such a way that it seems to have its own malignant
      presence, a 'malevolent third' (after Ogden 1994). I outline therapeutic
      interventions using the metaphor of the therapist as 'anti-director' and I
      introduce my concept of the conjoint selected fact (after Bion 1963 after
      Poincare 1952).

PMID- 16573751
TI  - How the mind understands other minds: cognitive psychology, attachment and
      reflective function.
AB  - Jung's epistemological relativistic attitude was very advanced for his time and
      very much in line with the contemporary philosophy of science. Further, Jung
      states that the patient's unconscious has the capacity to represent itself by
      creating metaphors which give the therapist all the help he might need in
      treating his patient. As such, Jungian analysts have not been encouraged to
      embark on theoretical work and as a result, the Jungian movement has been lacking
      those theories that connect general psychological principles with clinical
      practices. In an attempt to enlarge our 'middle-range theories', we shall discuss
      Peter Fonagy's concept of reflective function. In our opinion, the theoretical
      hypothesis regarding the instinct of reading the mind (Baron-Cohen 1995) and
      Fonagy's idea of reflective function are extremely useful in our Jungian clinical
      practice and these concepts are utilizable because they are not at odds with
      analytical psychology's general epistemological and theoretical framework.

PMID- 16573752
TI  - Jung, the trickster writer, or what literary research can do for the clinician.
AB  - This paper aims to show how literary scholarship can contribute to clinical
      debates by offering different methods of reading and interpreting works by Jung.
      Firstly, as texts form much of the means by which Jungian ideas are transmitted
      and worked upon, literary research offers methods of examining the way we read
      for authority and orthodoxy. Secondly, it is invaluable to look at the way in
      which Jung actually wrote. Jung portrays a dynamic psyche in action in his
      writings. His works are not only about a creative archetypal psyche, they enact
      and perform this creativity in the way in which he uses words. The rich
      playfulness demonstrated in The Collected Works is an example of a writer as a
      mythmaker of the psyche, one who absorbs unconscious creative energies into his
      writing in ways that dissolve modernity's cultural boundaries of science and art.
      In addition, the aesthetic component in Jung's writing is not a decoration of his
      ideas. Rather, his 'literary' qualities are themselves forms of argument about
      the fragile state of modern subjectivity. Using his essays on 'Synchronicity',
      and the 'Trickster', the paper will show these works to be responses to three
      related crises that still face clinicians and scholars today: the problematic
      role of the hero myth as an individuation narrative, the nature of 'science', and
      the crisis of western modernity itself in desperate need of psychic healing. The
      paper will show that where writing on synchronicity aims to individuate science
      by adding a 'feminine' Eros to its Logos biases, the Trickster essay is designed
      to ameliorate modernity by providing frameworks to make visible marginal or
      excluded material. In these works Jung tries to rejuvenate the modern world by re
      connecting traditional symbolic systems with the psyche through myth as a
      language of psychic relating.

PMID- 16573760
TI  - Autosomal dominant mutation causing the dorsal ridge predisposes for dermoid
      sinus in Rhodesian ridgeback dogs.
AB  - OBJECTIVES: To define the mode of inheritance of the dorsal ridge and investigate
      if the ridge predisposes to the congenital abnormality dermoid sinus in the
      Rhodesian ridgeback. METHODS: Segregation analysis was performed, including 87
      litters (n=803) produced in Sweden between 1981 and 2002. Data were corrected to
      avoid bias in the segregation ratio. Chi-squared analysis was performed including
      402 litters (n=3598) for the evaluation of a possible genetic correlation between
      the ridge and dermoid sinus. RESULTS: The ridge is inherited in an autosomal
      dominant mode and predisposes for dermoid sinus. The frequency of ridgeless
      offspring in the Swedish Rhodesian ridgeback population is estimated to be 5.6
      per cent. CLINICAL SIGNIFICANCE: Rhodesian ridgeback dogs that carry the ridge
      trait are predisposed to dermoid sinus.

PMID- 16573761
TI  - Analysis of canine and feline blood samples using the Kuadro in-house wet-reagent
      chemistry analyser.
AB  - OBJECTIVES: Kuadro is a new wet-reagent biochemistry analyser that is available
      for in-house use. The aim of this study was to compare the results produced by
      this analyser with those obtained by a wet-reagent analyser (KoneLab 30i) that
      served as the reference instrument. METHODS: Blood samples from 80 clinical cases
      (40 dogs and 40 cats) were analysed for urea, creatinine, total proteins,
      albumin, glucose, cholesterol, alanine aminotransferase, alkaline phosphatase,
      total bilirubin, amylase, total calcium, and phosphate using both the reference
      and Kuadro instruments. RESULTS: Kuadro performed very well on canine and feline
      samples, showing clinically acceptable correlations (r value) (canine/feline) for
      urea (0.99/0.97), creatinine (0.99/0.98), total proteins (0.95/0.97), albumin
      (0.98/0.90), glucose (0.99/0.99), cholesterol (0.99/0.99), alanine
      aminotransferase (1.00/0.99), alkaline phosphatase (0.96/0.99), total bilirubin
      (1.00/1.00), amylase (0.98/0.96), and phosphate (0.91/0.92). The correlation for
      total calcium measurements was clinically unacceptable (0.78/0.83). CLINICAL
      SIGNIFICANCE: Urea, creatinine, albumin, glucose, cholesterol, alanine
      aminotransferase, and phosphate Kuadro values can be used interchangeably with
      those generated by the reference analyser. Alkaline phosphatase, amylase, and
      total proteins Kuadro values cannot be used interchangeably, as Kuadro
      overestimated alkaline phosphatase and amylase and underestimated total protein
      measurements. Kuadro significantly underestimated total calcium concentrations
      due to the shorter incubation time used by the Kuadro analyser compared with the
      incubation time used in the reference analyser assay system.

PMID- 16573763
TI  - Ciclosporin treatment of suspected granulomatous meningoencephalomyelitis in
      three dogs.
AB  - Granulomatous meningoencephalomyelitis is an idiopathic disease of the central
      nervous system of presumed dysimmune origin. This disorder is characterised
      histologically by an angiocentric inflammatory reaction involving the brain, the
      spinal cord, and/or the leptomeninges. To date, the standard treatment for
      granulomatous meningoencephalomyelitis consists of immunosuppressive dosages of
      glucocorticoids. Ciclosporin A, a potent immunosuppressive agent that blocks the
      transcription of cytokine genes in activated T cells, has been proposed as a
      therapeutic alternative. In the present study of three dogs with suspected
      granulomatous meningoencephalomyelitis, microemulsified ciclosporin, at a dose of
      10 mg/kg once daily for at least six weeks, then reducing to 5 mg/kg daily, was
      administered after a variable period of glucocorticoid treatment, and resulted in
      a complete resolution of clinical signs. Satisfactory improvement of clinical
      signs after ciclosporin administration took more time than after glucocorticoid
      administration. Six weeks after the beginning of ciclosporin treatment, clinical
      results were similar to those obtained with prednisolone. Adverse effects were
      minimal with ciclosporin, with only intermittent vomiting.

PMID- 16573762
TI  - Cohort study of COX-1 and COX-2 expression in canine rectal and bladder tumours.
AB  - OBJECTIVES: To determine the role that cyclooxygenase-1 (COX-1) and
      cyclooxygenase-2 (COX-2) play in malignant transformation in canine transitional
      cell carcinoma and rectal tumours. METHODS: Histological sections of 21 canine
      rectal adenocarcinomas and 18 canine transitional cell carcinomas were stained
      for COX-1 and COX-2. Mann-Whitney non-parametric tests were applied to determine
      if there was any relationship between the percentage of cells expressing COX-1 or
      COX-2, and between COX-1 and COX-2 staining intensity and age, breed or sex.
      RESULTS: For rectal adenocarcinomas, 19.0 per cent of the sections were negative
      for COX-1 and COX-2. A further 38.1 per cent of the sections were negative for
      COX-2 but positive for COX-1, and 38.1 per cent of the sections had rare or
      occasional single cells positive for COX-2. No significant differences were found
      in COX staining when compared with age, breed or sex. For transitional cell
      carcinomas, all of the sections were positive for COX-1 and COX-2. For COX-2
      staining, 16.7 per cent had more than 30 per cent positive cells. For COX-1
      staining, 38.9 per cent had more than 30 per cent positive cells. There was a
      significant increase in the percentage of COX-1 positive cells in small breed
      dogs (P = 0.0337). CLINICAL SIGNIFICANCE: The variations in COX expression
      reported in this study may explain the differences in the clinical response of
      transitional cell carcinomas and rectal adenocarcinomas following treatment with
      non-steroidal anti-inflammatory drugs.

PMID- 16573764
TI  - Hypercalcaemia associated with granulomatous lymphadenitis and elevated 1,25
      dihydroxyvitamin D concentration in a dog.
AB  - A seven-year-old Labrador was presented with weight loss and mild generalised
      lymphadenopathy. Histopathology of an excised lymph node by the referring
      veterinarian demonstrated granulomatous lymphadenitis. At the time of referral,
      fine-needle aspirates of the lymph nodes confirmed the presence of ongoing
      granulomatous inflammation. Further investigations revealed marked
      hypercalcaemia, a low parathyroid hormone concentration, a parathyroid hormone
      related protein concentration within the reference range, and an elevated serum
      concentration of 1,25 dihydroxyvitamin D. An underlying cause of the
      granulomatous lymphadenitis could not be identified. The clinical signs,
      hypercalcaemia and elevated serum concentrations of 1,25 dihydroxyvitamin D
      resolved following prednisolone treatment. In contrast to dogs, hypercalcaemia
      occurred secondarily to granulomatous disease and elevated 1,25 dihydroxyvitamin
      D concentrations is a well-recognised condition in human beings. To the authors'
      knowledge, this is the first case report to describe elevated serum calcium and
      1,25 dihydroxyvitamin D concentrations in a dog with histologically confirmed
      granulomatous disease.

PMID- 16573766
TI  - Role of carboplatin in multi-modality treatment of canine tonsillar squamous cell
      carcinoma--a case series of five dogs.
AB  - Canine tonsillar squamous cell carcinoma is an aggressive disease with a poor
      prognosis. A retrospective study was undertaken of all dogs that were presented
      between January 1999 and January 2004 to the Animal Health Trust for the
      treatment of tonsillar squamous cell carcinoma. Five cases were identified, and
      their median survival time was 211 days (95 per cent confidence interval 80 to
      352) with two of the five dogs remaining alive at the end of the study, 826 and
      1628 days from diagnosis with no clinical signs of disease. The protocol was well
      tolerated with only one of the five dogs showing toxicity associated with
      carboplatin and all dogs that started radiotherapy completing it. Compared with
      results of previous studies, these cases suggest that surgical cytoreduction
      followed by coarse fractionated radiotherapy together with carboplatin may be a
      useful way to treat this tumour. Carboplatin alone caused partial remission in
      the two cases where it was used as neo-adjunctive therapy.

PMID- 16573765
TI  - Successful pregnancy following gonadotrophin-releasing hormone analogue treatment
      in a previously infertile bitch.
AB  - A Labrador retriever bitch was presented with repeated unsuccessful breeding
      during both the third and fourth oestruses, even though accurate timing for
      natural mating was planned based on the results obtained using a semiquantitative
      luteinising hormone kit and a quantitative assay of progesterone. To identify the
      problem, serum luteinising hormone, follicle-stimulating hormone, progesterone,
      and oestradiol-17beta concentrations around the fourth oestrus stage were assayed
      by radioimmunoassay. Abnormal luteinising hormone fluctuations were detected
      during pro-oestrus and oestrus, and lower than normal progesterone concentrations
      were found during the mating period. In the fifth to seventh oestrus, the bitch
      was successfully treated with gonadotrophin-releasing hormone analogue at times
      based on the findings of the hormonal assays.

PMID- 16573767
TI  - Aortic foreign body (airgun pellet) embolism in a cat.
AB  - A five-year-old female domestic shorthair cat presented with clinical signs
      typical of an aortic saddle thromboembolism. An echocardiogram and thoracic
      radiographs excluded cardiac disease as a source of the thrombus. Two heavy metal
      opacity, pellet-like objects were seen in the thoracic and abdominal radiographs.
      Abdominal ultrasound demonstrated occlusion of aortic blood flow by the abdominal
      pellet but could not indicate whether this was due to a penetrating aortic wound
      or pellet embolisation. A necropsy confirmed a penetrating left ventricular
      cardiac wound with subsequent embolisation of the pellet to the abdominal aorta.

PMID- 16573768
TI  - What is your diagnosis? Babesia canis and canine distemper virus.

PMID- 16573771
TI  - Push-and-pull enteroscopy using the double-balloon technique (double-balloon
      enteroscopy) for the diagnosis of Meckel's diverticulum in adult patients with GI
      bleeding of obscure origin.
AB  - BACKGROUND: Meckel's diverticulum (MD) occurs in 2-3% of the population. Although
      the clinical, histopathologic, and radiologic features of the complications of MD
      are well known, the diagnosis may be difficult before surgery. CASE REPORT: Three
      patients (age 22-34 yr, two women) presenting with gastrointestinal (GI) bleeding
      of obscure origin underwent multiple endoscopic and radiologic tests including
      capsule endoscopy and Tc-99m pertechnetate scintigraphy before push-and-pull
      enteroscopy using a double-balloon technique (double-balloon enteroscopy). Double
      balloon enteroscopy was performed in all three patients using oral and anal
      approaches to evaluate the entire intestine. In one case, MD was detected using
      the oral route; the diagnosis was confirmed using the anal approach. In two
      patients, the lumen of MD was disclosed using the anal route. No procedure
      related complications occurred. Push-and-pull enteroscopy was the only
      nonsurgical procedure that provided a precise diagnosis. All patients underwent
      surgical resection of the diverticulum. In one case, ectopic gastric tissue was
      found histologically. No further bleeding occurred during follow-up (6-9 months).
      CONCLUSIONS: Keeping the low sensitivity of Tc-99m scintigraphy in the adult
      population in mind, double-balloon enteroscopy might be the modality of choice in
      young adult patients with acute recurrent GI bleeding of obscure origin and a
      suspected diagnosis of MD.

PMID- 16573772
TI  - Cysteinyl leukotriene levels in esophageal mucosal biopsies of children with
      eosinophilic inflammation: are they all the same?
AB  - OBJECTIVES: Allergic eosinophilic esophagitis (AEE) is characterized by intense
      eosinophilic inflammation of the esophageal mucosa. Cysteinyl leukotrienes
      (CysLT) are eosinophil chemoattractants. We studied CysLT levels in esophageal
      mucosa of children with AEE and controls. METHODS: CysLT levels (pg CysLT/microg
      protein) were quantified by Enzyme-linked Immunosorbent Assay (ELISA) on
      endoscopically obtained esophageal mucosal biopsies. RESULTS: Twelve children
      with AEE (eight boys, mean age 6.6 yr, range 1.0-14.5 yr) and 10 controls (six
      boys, mean age 9.56 yr, range 1.08-15.08 yr) were enrolled. None were on anti-LT
      or corticosteroid therapy. All controls had histologically normal mucosal
      biopsies of the esophagus, stomach, and duodenum. Patients with AEE had intense
      eosinophilic inflammation of the esophageal mucosa (mean 39 eosinophils/hpf,
      range 15-70 eosinophils/hpf) and a normal 24-h pH probe study. CysLT levels were
      similar between the two groups: mean levels were 12.44 (median 10.87, range 2.54
      28.29) in AEE patients and 9.52 (median 9.26, range 1.71-21.64) in controls.
      CysLT levels did not correlate with the degree of esophageal eosinophilic
      inflammation. Incidentally, five patients with eosinophilic gastroduodenitis, in
      addition to esophagitis, were enrolled; their CysLT levels were statistically
      higher than those of controls. CONCLUSIONS: This is the first study to examine
      CysLT levels in esophageal mucosal biopsies of children with AEE and normal
      children. CysLT levels in AEE patients are similar to those in controls, and
      independent of the severity of inflammation. While this would argue against the
      use of CysLT antagonists in the treatment of AEE, further studies into the
      expression of the CysLT receptor itself are needed.

PMID- 16573773
TI  - Barrett's esophagus and medications that relax the lower esophageal sphincter.
AB  - OBJECTIVES: Medications that may increase gastroesophageal reflux could be risk
      factors for esophageal adenocarcinoma; however, epidemiologic studies present
      conflicting results. We evaluated patients with a high-risk condition, Barrett's
      esophagus, to identify risk factors that may act early in the carcinogenic
      process. METHODS: We conducted a nested case-control study within a large
      integrated health-services organization. Electronic databases were used to
      identify incident diagnoses of Barrett's esophagus (cases); two controls were
      matched to each case. Electronic databases provided information on the use of
      medications that may induce reflux (nitrates, calcium channel blockers,
      xanthines, benzodiazepines, and beta agonists) and potential confounders. A
      supplemental mailed questionnaire evaluated additional potential confounders.
      RESULTS: We identified 421 cases and selected 842 controls. The association
      between any medication use and a Barrett's esophagus diagnosis was modified by
      age; an increased risk was observed only among subjects <70 yr of age (adjusted
      odds ratio [OR] = 2.6; 95% confidence interval [CI] 1.5-4.6). A Barrett's
      esophagus diagnosis was associated with asthma medication use (OR 5.8; 95% CI
      2.2, 14.9), but not with the other medications studied. Subgroup analyses
      suggested that medication use was not independently associated with reflux
      symptoms and that adjustment for asthma symptoms substantially reduced the
      association between medication use and a Barrett's esophagus diagnosis.
      CONCLUSION: The use of medications that may induce reflux was associated with a
      Barrett's esophagus diagnosis among younger persons. This association was only
      observed with asthma medications; the analyses suggested the possibility of
      confounding by indication, whereby reflux may cause both asthma and Barrett's
      esophagus.

PMID- 16573774
TI  - Reports of "satisfactory relief" by IBS patients receiving usual medical care are
      confounded by baseline symptom severity and do not accurately reflect symptom
      improvement.
AB  - BACKGROUND: Treatment trials for irritable bowel syndrome (IBS) usually define a
      responder as a patient who reports satisfactory relief or adequate relief of
      symptoms at the end of the trial. However, these measures have not been
      adequately validated. AIMS: (1) Compare a binary satisfactory relief measure to
      alternative ways of defining a treatment responder. (2) Determine whether
      baseline IBS symptom severity or psychological distress influence the sensitivity
      of these outcome measures. METHODS: A total of 350 patients (81% females, average
      age 50 yr) who had a medical diagnosis of IBS and satisfied Rome II criteria,
      were recruited from Group Health Cooperative of Puget Sound. At baseline the
      Irritable Bowel Severity Scale (IBSS) was used to assess symptom severity and to
      classify patients as mild, moderate, or severe. Psychological distress and IBS
      specific quality of life (IBS-QOL) were also assessed. After 6 months treatment
      with standard medical care, IBSS and IBS-QOL were reassessed, and patients were
      asked whether they had experienced satisfactory relief and whether they were
      somewhat or markedly better. RESULTS: Initial severity of IBS significantly
      affected the proportion who reported satisfactory relief (mild, 72%; moderate,
      53%; severe, 44%) and the proportion who were somewhat or markedly better (mild,
      62%; moderate, 44%; severe, 38%), but did not affect the proportion with a 50%
      reduction in symptoms (mild, 26%; moderate, 25%; severe, 23%). Although mild
      patients were the most likely to report satisfactory relief, they showed no
      average decrease in symptom severity or improvement in IBS-QOL. Conversely,
      severe patients, who were the least likely to report satisfactory relief, had the
      largest reductions in IBS symptom severity and the largest improvements in IBS
      QOL. Psychological distress had no significant effect on the responder rate after
      adjusting for IBS symptom severity. CONCLUSIONS: These data from a descriptive
      study suggest that satisfactory relief is confounded with initial IBS symptom
      severity and is poorly correlated with the amount of symptom improvement.
      Confirmation of these findings in a clinical trial is needed.

PMID- 16573775
TI  - Investigating the hygiene hypothesis as a risk factor in pediatric onset Crohn's
      disease: a case-control study.
AB  - BACKGROUND AND OBJECTIVES: Evidence for the hygiene hypothesis in the etiology of
      Crohn's disease (CD) is unclear. We investigated the relationship between
      infection-related exposures and risk for CD in children. METHODS: A hospital
      based case-control was carried out. Newly-diagnosed cases of CD (n = 194), less
      than 20 yr of age were recruited from the gastroenterology clinic of a large
      pediatric inflammatory bowel disease (IBD) center in Montreal, Canada. Orthopedic
      patients pair-matched (n = 194) for timing of diagnosis and area of residence
      were recruited as controls. Information on infection-related exposures between
      birth and disease diagnosis was ascertained by administering a structured
      questionnaire to the mother and the index subject. The relationship between the
      frequency and timing of infection-related exposures with CD was studied. RESULTS:
      The mean age (SD) at diagnosis was 12.3 (5.1). CD was more common after 10 yr of
      age. Gender distribution was similar between comparison groups. In multivariate
      conditional logistic regression, family history of IBD (odds ratio (OR) = 4.6;
      95% confidence interval (CI) = 1.6-13.3), age (OR = 1.2; 95% CI = 1.1-1.3), and
      owning a pet (OR = 2.0; 95% CI = 0.9-4.5) were associated with risk for CD,
      whereas regular use of a personal towel (OR = 0.5; 95% CI = 0.2-0.9) and lesser
      crowding in homes (OR = 0.3; 95% CI = 0.1-0.8) were protective. Day-care
      attendance during the first 6 months of life and "physician-diagnosed infections"
      between 5 and 10 yr of age were associated with increased risks for CD.
      CONCLUSIONS: Infection-related exposures seem to enhance risk for CD in children.
      The timing of these exposures during early childhood may be relevant to the
      etiology of pediatric CD.

PMID- 16573776
TI  - Functional heartburn patients demonstrate traits of functional bowel disorder but
      lack a uniform increase of chemoreceptor sensitivity to acid.
AB  - BACKGROUND: Functional heartburn (FH) patients have a profound impact on the
      response to anti-reflux therapy of the nonerosive reflux disease (NERD) group as
      compared to the response of the erosive esophagitis group. Thus far, there is
      paucity of information about their physiological and clinical characteristics
      that may separate them from the other NERD patients. AIM: To compare
      physiological and clinical characteristics of patients with FH to their
      counterparts within the NERD group (NERD-positive [NERD+]). METHODS: Subjects
      with typical heartburn symptoms, at least twice a week, were evaluated by an
      upper endoscopy. Only those with normal esophageal mucosa were recruited into the
      study and underwent pH testing to assess esophageal acid exposure. The patients
      were divided into those with normal pH test (FH) and those with abnormal pH test
      (NERD+). The groups were compared for demographics, gastroesophageal reflux
      disease symptom characteristics, psychological profile, and reported quality of
      life. Additionally, the two patient groups were compared for stimulus response
      functions to acid, autonomic function response, and rate of Helicobacter pylori
      infection. RESULTS: Fifty-two patients included 30 with FH and the rest with
      NERD+. There was no statistical difference in demographics, frequency of hiatal
      hernia and H. pylori infection between the two groups. Patients with FH had a
      significantly longer history of heartburn and reported more episodes of chest
      pain than NERD+ patients (M--7.5 yr and M--once a week vs M--3.5 yr and M--once a
      month, respectively, p < 0.05). Patients with FH scored significantly higher in
      the somatization domain than patients with NERD+ (M--60 vs 52.5, p < 0.05), but
      had similar reported quality of life. Patients with NERD+ demonstrated a
      significantly shorter time to symptom perception and higher intensity rating (p <
      0.05). Only patients with FH demonstrated a statistically significant increase in
      heart rate and skin conductance after acid perfusion, as compared to those with
      NERD+ (p < 0.05). CONCLUSION: Patients with FH demonstrate increased reports of
      chest pain and somatization, an alteration in autonomic function but lack a
      uniform increase in chemoreceptor sensitivity to acid as compared to those with
      NERD+. This suggests that while FH patients harbor clinical traits of a
      functional bowel disorder, hypersensitivity to acid is not a general phenomenon.

PMID- 16573777
TI  - Tacrolimus is safe and effective in patients with severe steroid-refractory or
      steroid-dependent inflammatory bowel disease--a long-term follow-up.
AB  - OBJECTIVE: We and others have reported the use of tacrolimus in refractory
      inflammatory bowel disease (IBD). Little is known about its long-term efficacy
      and safety. METHODS: In this retrospective, observational single center study the
      charts of 53 adult patients with steroid-dependent (n = 18) or steroid-refractory
      (n = 35) IBD, Crohn's disease (CD) (n = 11), ulcerative colitis (UC) (n = 40), or
      pouchitis (PC) (n = 2) were reviewed. Tacrolimus (0.1 mg/kg body weight per day)
      was administered orally in all and initially intravenously in 2 patients (0.01
      mg/kg body weight per day), aiming for serum trough levels of 4-8 ng/mL. Forty
      one of 53 (77.1%) patients were receiving concomitant azathioprine. The mean
      treatment duration was 25.2 +/- 4.6 SD months (0.43-164 months). Patients were
      followed for a mean of 39 +/- 4.1 SD months (5-164 months). Response was
      evaluated using a modified clinical activity index (M-CAI). RESULTS: Thirty-one
      UC (78%), 10 CD (90.1%), and both PC (100%) patients experienced an immediate
      clinical response or went into remission at 30 days. A statistically significant
      drop on the M-CAI was documented for UC and CD patients. Nine UC patients (22.5%)
      underwent colectomy between 1.6 and 41.3 months following initiation. Mean
      colectomy-free survival was 104.8 +/- 15.5 (95% CI 74.4-135.2) months (limited to
      164.4 months). Cumulative colectomy-free survival was estimated 56.5% at 43.8
      months. Steroids were reduced or discontinued in 40 of 45 UC and CD patients
      (90%) taking steroids. Side effects included a temporary rise of creatinine (n =
      4, 7.6%), tremor or paresthesias (n = 5, 9.4%), hyperkalemia (n = 1, 1.9%),
      hypertension (n = 1, 1.9%), and opportunistic infections (n = 2, 3.8%).
      CONCLUSION: Long-term tacrolimus therapy appears safe and effective in refractory
      IBD.

PMID- 16573778
TI  - Complicated and uncomplicated peptic ulcers in a Danish county 1993-2002: a
      population-based cohort study.
AB  - Peptic ulcer epidemiology changes as the proportion of Helicobacter pylori
      infected people decreases, use of nonsteroidal anti-inflammatory drugs (NSAID)
      increases, and the proportion of elderly persons increases. OBJECTIVES: To
      describe incidence and prognosis of uncomplicated and complicated peptic ulcer
      patients in Funen County 1993-2002. METHODS: Data on endoscopies, gastric and
      duodenal operations, and related peptic ulcer diagnoses were extracted from four
      population-based databases covering a period from 1974 to 2002. All citizens of
      Funen County (population 470,000) who between 1993 and 2002 had a peptic ulcer
      diagnosed for the first time were identified. RESULTS: Between 1993 and 2002 the
      incidence of uncomplicated duodenal ulcer decreased from 0.55/1,000 person-years
      (95% CI 0.49-0.62) to 0.37 (0.31-0.43), uncomplicated gastric ulcer decreased
      from 0.56 (0.49-0.63) to 0.40 (0.34-0.46), and perforated ulcer decreased from
      0.14 (0.11-0.18) to 0.08 (0.06-0.11). The incidence of bleeding peptic ulcer was
      stable with 0.55 (0.49-0.62) in 1993 and 0.57 (0.51-0.64) in 2002. The proportion
      of possible NSAID-related incident peptic ulcers increased from 320/827 (39%) in
      1993 to 363/686 (53%) in 2002 (p < 0.01). A total of 3,233 patients with incident
      complicated peptic ulcer (9,927 person-years) and 4,421 patients with incident
      uncomplicated peptic ulcer (17,773 person-years) was followed for up to 10 yr.
      The first month following newly diagnosed complicated ulcer the standardized
      mortality rate was 37.1 (33.4-41.1) during the next 11 months it was 5.1 (4.6
      5.6), and in the following years it was 2.6 (2.4-2.8). The corresponding figures
      for incident uncomplicated peptic ulcer was 11.6 (9.6-13.9), 4.0 (3.6-4.4), and
      2.5 (2.3-2.7). CONCLUSION: During the period, incidence of peptic ulcers
      decreased and an increasing proportion was related to NSAID. Mortality is high.

PMID- 16573779
TI  - Association of intestinal granulomas with smoking, phenotype, and serology in
      Chinese patients with Crohn's disease.
AB  - INTRODUCTION: Crohn's disease (CD) is a heterogenous disease characterized by
      variable manifestations and outcomes, and increasing in incidence in China.
      Phenotypic classification has been proposed to assist in subtyping of disease.
      Non-caseating intestinal granulomas are a hallmark of CD, but whether intestinal
      granulomas help predict Chinese CD phenotypes or determine severity, is not
      known. AIMS: To determine the association between intestinal granulomas with CD
      phenotype, severity, risk factors, and serological markers. METHODS: This was a
      single-centre study of consecutive definite Chinese CD cases. Granulomas were
      diagnosed by an experienced GI pathologist. Correlation with the Vienna
      Classification and other parameters was performed. RESULTS: Eighty Chinese CD
      patients were recruited, 40 (50%) of whom had intestinal granulomas. Intestinal
      granulomas were independently associated with the stricturing behavior (OR: 4.71;
      95% CI: 1.41-15.72), colonic location of disease (OR: 26.96; 95% CI: 2.68
      271.14), but not with age of CD diagnosis. Current or previous smoking protected
      against the development of granulomas (OR: 0.16; 95% CI: 0.04-0.59). Granulomas
      were not associated with peri-anal involvement, extra-intestinal manifestations,
      anti-neutrophil cytoplasmic antibody or anti-Saccharomyces cerevisiae antibody
      serology, or severity of CD gauged by the requirement of major intestinal surgery
      or immunomodulating therapy. CONCLUSIONS: Intestinal granulomas in the setting of
      CD may be helpful in determining phenotypic subtypes of CD, but is unhelpful in
      predicting disease severity. Smoking impairs the formation of granulomas in CD.

PMID- 16573780
TI  - TNFalpha and IL-10 gene polymorphisms in inflammatory bowel disease. Association
      of -1082 AA low producer IL-10 genotype with steroid dependency.
AB  - OBJECTIVES: An altered production of cytokines underlies inflammatory bowel
      disease (IBD) susceptibility. Various polymorphisms at the IL-10 and TNFalpha
      gene promoters control cytokine production levels. The influence of these
      polymorphisms on susceptibility to ulcerative colitis (UC) and Crohn's disease
      (CD) and their association with clinical features were analyzed. SUBJECTS AND
      METHODS: Genetic polymorphisms of TNFalpha (-308 G/A) and IL-10 (-1082 G/A, -812
      C/T, and -592 C/A) were determined using the LightCycler system with
      hybridization probes matched with one sequence variant. The study population
      included 99 UC patients, 146 CD patients, and 343 matched controls. RESULTS: We
      did not find association between TNFalpha or IL-10 gene polymorphisms and UC or
      CD susceptibility, though a slight influence of -1082*G allele in UC appearance
      was observed. In a stratified analysis, a highly significant association between
      the -1082 AA IL-10 genotype and the steroid dependency was observed in IBD (p <
      0.0001), contributing both UC (p = 0.004) and CD (p = 0.003) to this association.
      In contrast, TNFalpha genotypes did not influence steroid dependency in IBD.
      Further, the contribution of cytokine genotypes and of clinical features to the
      appearance of steroid-dependent status (dependent variable) was studied by
      multivariate analysis. The steroid-dependent phenotype correlated in UC with
      extensive disease (p = 0.010) and with the low producer -1082 AA IL-10 genotype
      (p = 0.002) and in CD with penetrating disease (p = 0.010), arthritis (p =
      0.011), and the -1082 AA IL-10 genotype (p = 0.006). CONCLUSIONS: The main
      conclusion is that carriage of the -1082 AA IL-10 genotype (low producer) is a
      relevant risk factor for developing steroid-dependent IBD.

PMID- 16573781
TI  - Endoscopic sedation in the United States: results from a nationwide survey.
AB  - OBJECTIVES: The introduction of new sedative agents as well as a desire for
      improved patient satisfaction and greater efficiency has changed the practice of
      endoscopic sedation. This survey was designed to provide national and regional
      data on endoscopic sedation and monitoring practices within the United States.
      METHODS: A 22-item survey regarding current practices of endoscopy and sedation
      was mailed to 5,000 American College of Gastroenterology physician members
      nationwide. RESULTS: A total of 1,353 questionnaires (27.1%) were returned.
      Respondents performed an average of 12.3 esophagogastroduodenoscopies (EGDs) and
      22.3 colonoscopies per wk. Endoscopic procedures were performed within a hospital
      setting (55.2) more often than at an ambulatory center (35.8%) or private office
      (8.8%). The vast majority of EGDs and colonoscopies (>98%) were performed with
      endoscopic sedation. Almost three quarters (74.3%) of the respondents used a
      narcotic and benzodiazepine for sedation, while propofol was preferred by 25.7%.
      Sedation practices varied considerably within different geographic regions of the
      United States. Respondents routinely monitored vital signs and pulse oximetry
      (99.2% and 98.6%, respectively), and supplemental oxygen was administered to all
      patients during EGD by 72.7% of endoscopists. Endoscopist satisfaction with
      sedation was greater among those using propofol than conventional sedation (10 vs
      8, p < 0.0001). CONCLUSIONS: During the past 15 yr, the volume of procedures
      performed by endoscopists in the United States has increased two- to fourfold.
      Propofol is currently being used for sedation in approximately one quarter of all
      endoscopies in the United States. The findings from this survey may help in the
      formulation of updated policies and practice guidelines pertaining to endoscopic
      sedation.

PMID- 16573782
TI  - Preservation of gastric acid secretion may be important for the development of
      gastroesophageal junction adenocarcinoma in Japanese people, irrespective of the
      H. pylori infection status.
AB  - BACKGROUND: We have previously reported that Helicobacter pylori infection
      prevents reflux esophagitis (RE) and Barrett's esophagus (BE) by decreasing
      gastric acid secretion. Gastroesophageal (GE) junction adenocarcinoma, including
      Barrett's adenocarcinoma, has been thought to be a complication of
      gastroesophageal reflux disease (GERD). However, the relationship between H.
      pylori infection, gastric acid secretion, and GE junction adenocarcinoma has not
      yet been investigated in Japan. The aim of this study was to evaluate this
      relationship in the Japanese population. METHODS: A total of 168 Japanese
      patients (RE alone: 80, short-segment BE (SSBE): 16, long-segment BE (LSBE): 20,
      GE junction adenocarcinoma: 12, distal early gastric cancer (EGC): 40;
      male/female = 106/62; mean age 61.5 yr) and 80 Japanese control subjects who had
      no localized lesions in the upper gastrointestinal tract (male/female = 43/37,
      mean age 58.1 yr) were enrolled for this study. The prevalence of H. pylori
      infection was determined by biopsy, the rapid urease test, and measurement of the
      serum H. pylori IgG antibody. Gastric acid secretion was assessed by the
      endoscopic gastrin test (EGT). RE was diagnosed according to the Los Angeles
      classification. RESULTS: The prevalence of H. pylori infection in the patients
      with RE alone (30%) was significantly lower than that in control subjects
      (71.2%). There was also a tendency for the prevalence of H. pylori infection to
      be lower in patients with BE (SSBE, 18.7%; LSBE, 0%) when compared to that in
      patients with RE alone. On the other hand, while the prevalence of H. pylori
      infection in patients with GE junction adenocarcinoma (58.3%) was significantly
      lower than that in patients with EGC (87.5%), it tended to be higher than that in
      patients with RE alone or BE. The mean EGT value in patients with RE alone (3.74
      mEq/10 min) was significantly higher than that in control subjects (1.83). The
      mean EGT value in patients with BE (SSBE, 4.74; LSBE, 4.76) tended to be even
      higher than that in patients with RE alone. The mean EGT value in patients with
      GE junction adenocarcinoma (3.94) was significantly higher than that in control
      subjects and patients with EGC (0.67), but it was comparable to that independent
      of the H. pylori infection status in patients with RE alone or BE. CONCLUSION:
      Preservation of gastric acid secretion may be important for the development of GE
      junction adenocarcinoma in Japanese people, irrespective of the H. pylori
      infection status.

PMID- 16573783
TI  - Risk factors for obstruction, perforation, or emergency admission at presentation
      in patients with colorectal cancer: a population-based study.
AB  - OBJECTIVES: Previous studies have shown that patients newly diagnosed with
      colorectal cancer (CRC) requiring emergency admission to hospital or those
      presenting with obstruction or perforation (defined here as OPE) have advanced
      disease. The objective was to conduct a population-based study among persons with
      a new diagnosis of CRC to identify factors associated with OPE in Ontario.
      METHODS: We analyzed data from the following databases: Canadian Institute for
      Health Information (CIHI), the Ontario Health Insurance Plan (OHIP), and the
      Registered Persons Database (RPDB). We identified all individuals > or = 20 yr of
      age with a new diagnosis of CRC (ICD-9 codes 153.0-153.4, 153.6-154.1) during
      1996-2001 and defined the first admission for CRC as the index admission. We
      excluded those who received chemotherapy, radiotherapy, or palliative care prior
      to the index admission. We identified those with concomitant obstruction (ICD-9
      code 560.9), perforation (ICD-9 code 569.8), or who were classified as emergency
      admission (referred to as OPE). Adjusted risk of OPE was calculated using
      logistic regression analysis. RESULTS: Between 1996 and 2001, we identified
      41,356 persons with CRC, of whom 53.5% were men. In logistic regression analysis,
      female sex and low income were significantly associated with OPE, after adjusting
      for differences in age, cancer site, previous large bowel evaluation,
      comorbidity, having a regular source of primary care, and year of diagnosis. For
      men the adjusted odds ratio (OR) for OPE was 0.93 (95% confidence interval (CI)
      0.88-0.99), and for the highest-income quintile the adjusted OR was 0.78 (95% CI
      0.72-0.85). CONCLUSION: Among persons with a new diagnosis of CRC in Ontario,
      women and those who are poor are more likely to present with obstruction,
      perforation, or emergency admission to hospital. Population-based CRC screening
      is needed to address these adverse outcomes.

PMID- 16573784
TI  - A common polymorphism in the interleukin 8 gene promoter is associated with
      Clostridium difficile diarrhea.
AB  - OBJECTIVE: Mucosal interleukin 8 (IL-8) and neutrophil recruitment are central to
      the pathogenesis of Clostridium difficile (CD) toxin-induced diarrhea (CDD). We
      hypothesized that like other inflammatory mucosal infections, susceptibility to
      CDD would relate to genetically determined variations in the production of IL-8.
      METHODS: Fecal IL-8 production and single nucleotide polymorphism (SNP) frequency
      in the -251 region of the IL-8 gene were determined in hospitalized patients: 42
      with CDD, 42 with CD-negative diarrhea, and 41 without diarrhea. Cases and
      controls were matched by age, length of hospital stay, comorbidity, and receipt
      of antibiotics. RESULTS: An association was found between the IL-8 -251 A/A
      allele and occurrence of CDD, 39%versus 16% (OR = 3.26, 95% CI 1.09-9.17) and 17%
      (OR = 5.50, 95% CI 1.22-24.8) for the two control groups. Comparing results by IL
      8 genotype for the CDD cases, median and mean fecal IL-8 levels were
      significantly higher for the -251 A/A genotype (p = 0.03 for median and 0.001 for
      mean). CONCLUSIONS: These studies indicate a common SNP in the IL-8 gene is
      associated with increased susceptibility to CDD and with increased fecal IL-8 in
      diarrheal stools.

PMID- 16573785
TI  - Proposal of a modified Cancer of the Liver Italian Program staging system based
      on the model for end-stage liver disease for patients with hepatocellular
      carcinoma undergoing loco-regional therapy.
AB  - BACKGROUND: The Cancer of Liver Italian Program (CLIP) system was suggested as
      the primary staging system for hepatocellular carcinoma (HCC). The model for end
      stage liver disease (MELD) is a better prognostic predictor for cirrhotic
      patients compared to Child-Turcotte-Pugh (CTP) system, which is a parameter used
      in the CLIP model. AIM: To investigate the performance of the modified MELD-based
      CLIP systems. METHODS: The CTP class in the CLIP model was replaced with MELD
      score (<10, 10-14, >14; modified CLIP-1), or additional 1 or 2 points were given
      to patients with MELD score 10-14 or >14, respectively (modified CLIP-2). The
      modified CLIP systems were compared with the original system in 343 HCC patients
      undergoing loco-regional therapy. RESULTS: The original CLIP score in all
      patients was 1.2 +/- 1.1 (range 0-5), compared with 1.4 +/- 1.2 (range 0-5) for
      modified CLIP-1 and 1.7 +/- 1.4 (range 0-6) for modified CLIP-2 models (p <
      0.001). Using mortality as the endpoint, the area under receiver operating
      characteristic curve for modified CLIP-2 system was 0.858 compared with 0.812 for
      modified CLIP-1 (p = 0.013) and 0.782 for original CLIP system (p < 0.001) at 12
      months; the area was 0.879, 0.830, and 0.762, respectively (p all < 0.001) at 24
      months. Survival analysis showed that the modified CLIP systems had a better long
      term discriminatory ability for different score groups. CONCLUSIONS: The CLIP
      model is useful to predict the outcome in HCC patients undergoing loco-regional
      therapy. The MELD-based modified CLIP systems may have a better predictive
      ability than the original model for cancer staging.

PMID- 16573786
TI  - Portal hypertensive gastropathy in chronic hepatitis C patients with bridging
      fibrosis and compensated cirrhosis: results from the HALT-C trial.
AB  - OBJECTIVES: The clinical significance of portal hypertensive gastropathy (PHG) in
      patients with compensated liver disease is not well established. The aim of this
      study was to determine the prevalence and correlates of PHG in a large cohort of
      patients with chronic hepatitis C virus (HCV) infection and bridging
      fibrosis/compensated cirrhosis entering the randomized phase of the Hepatitis C
      Antiviral Long-term Treatment against Cirrhosis trial (HALT-C). METHODS: The
      presence and severity of PHG in 1,016 HCV patients with no prior history of
      gastrointestinal bleeding was determined at surveillance endoscopy using the New
      Italian Endoscopy Club criteria. RESULTS: Overall, 37% of HALT-C patients had PHG
      with 34% having mild and 3% with severe changes. The mucosal mosaic pattern was
      identified in 33%, red marks in 15%, and gastric antral vascular ectasia (GAVE)
      features in only 3%. Independent correlates of PHG included biochemical markers
      of liver disease severity (lower serum albumin, higher bilirubin), portal
      hypertension (lower platelet count), insulin resistance (higher glucose), and non
      African American race. Independent correlates of GAVE included a history of
      smoking, nonsteroidal anti-inflammatory drugs (NSAIDs) use within the past year,
      and higher serum bilirubin and glucose levels. There was a strong positive
      association between the presence of PHG and esophageal varices (p < 0.0001).
      CONCLUSIONS: PHG is associated with the histological and biochemical severity of
      liver disease in patients with HCV and advanced fibrosis but is mild in most
      patients. The clinical relevance of these findings will be further explored
      during the randomized phase of the HALT-C study.

PMID- 16573787
TI  - Systematic review: the use of mesalazine in inflammatory bowel disease.
AB  - BACKGROUND: Mesalazine is among the medications most commonly prescribed by
      gastroenterologists, having to a large extent superseded sulfasalazine
      (sulphasalazine). However, there are still a number of aspects regarding its use
      which provoke debate and controversy. AIM: To provide a systematic assessment of
      the evidence for the use of mesalazine in ulcerative colitis and Crohn's disease.
      METHODS: References were identified using PubMed database. Additional references
      were identified with related article searches. RESULTS: Mesalazine has a clear
      role in the maintenance of remission in ulcerative colitis and management of mild
      to moderately active disease, although the efficacy of topical preparations or
      combined topical and oral is clearly superior to oral alone. Evidence that
      increasing the dose of oral mesalazine improves efficacy is not clear-cut. The
      benefits of mesalazine in the management of acute Crohn's disease and the
      maintenance of remission are questionable and alternative treatments are usually
      more appropriate. Emerging evidence suggests that maintenance mesalazine reduces
      the risk of neoplastic progression in chronic ulcerative colitis. Compliance with
      therapy is thus important, as is an understanding of individuals most likely to
      default on this. CONCLUSION: Evidence for a beneficial effect of mesalazine is
      largely confined to the management of ulcerative colitis.

PMID- 16573789
TI  - Personal view: the paradox of runaway competitions in gastroenterology.
AB  - Occasionally, gastroenterologists harbour reservations about the appropriateness
      of various procedures and management options, yet find themselves drawn into a
      competition and forced by outside exigencies to provide such services. The aim of
      the present analysis was to describe patterns of runaway competitions and factors
      that influence their occurrence in gastroenterology. The interactions between two
      physicians or physician and patient are modelled as non-zero-sum games of two
      players. The outcomes associated with two behavioural strategies of two players
      are arranged in a two-by-two game matrix. Many scenarios of clinical
      gastroenterology and social interactions among gastroenterologists are
      characterized by the underlying game of prisoner's dilemma, where two players can
      choose to co-operate or compete with each other. Although from their joint
      perspective co-operation results in a higher joint utility, the perspective of
      each individual favours competition. Following the inescapable logic of their
      individual perspective, the players end up with a worse outcome than through co
      operation. A runaway competition ensues if the game is played repeatedly with
      players successively increasing their stakes. Ultimately, each player tries to
      outdo the opponent while heading in the wrong direction. Recognizing the
      hallmarks of the game of prisoner's dilemma may help gastroenterologists to avoid
      such competitions.

PMID- 16573788
TI  - Personal view: the management of chronic hepatitis B infection.
AB  - There are two new nucleoside analogues available for the management of chronic
      hepatitis B, adefovir and entecavir, and several more in development. In
      addition, pegylated interferon has become available. Large-scale population
      studies have re-emphasized the significance of viral load in predicting a poor
      outcome over the longer term. These new developments have prompted a reassessment
      of the indications and objectives of therapy for chronic hepatitis B. Hepatitis B
      virus deoxyribonucleic acid, rather than alanine aminotransferase should be the
      prime indication for therapy. Hepatitis B e antigen seroconversion can be
      achieved in 30-40% of treated patients whatever agent is used. However, it takes
      longer for nucleoside analogues to achieve the same seroconversion rates as
      interferon. In anti-HBe-positive disease long-term therapy is required for most
      patients because the relapse rate after withdrawal of therapy is very high,
      irrespective of the agent used. Viral resistance limits the use of lamivudine,
      and to a lesser extent adefovir. Resistance to entecavir has so far only been
      described in pre-existing lamivudine resistance. Although therapy with
      combinations of nucleoside analogues has not been investigated to any extent,
      this is the only way to reduce the emergence or resistance, and studies are
      urgently needed.

PMID- 16573790
TI  - Personal view: adequate relief as a primary endpoint in irritable bowel syndrome.
AB  - The success of a clinical trial is judged by achieving statistical and clinical
      significance on the primary endpoint. This is particularly relevant in those
      trials that are initiated to achieve regulatory approval of a new therapeutic
      agent. Selection of an endpoint for which statistical significance will be too
      difficult to achieve can result in clinical trial data that fails to meet
      regulatory requirements for product approval. Over the past decade, significant
      progress has been made in development and refinement of the study design for
      evaluating new therapeutic agents targeted for the treatment of irritable bowel
      syndrome. One aspect of trial design that has been advanced is recognition of the
      endpoint of 'Adequate Relief.' Adequate relief has been used as a primary
      endpoint in treatment trials with alosetron, cilansetron and dextofisopam. With
      each of these agents, statistically significant benefit was seen when compared to
      placebo. As an endpoint, adequate relief is responsive, reproducible and moves in
      the same direction as other meaningful measures, and, therefore, displays
      properties of a validated endpoint. Adequate relief should be considered an
      acceptable primary endpoint by regulatory agencies for use in clinical trials of
      novel therapeutic agents for irritable bowel syndrome.

PMID- 16573791
TI  - Risk factors, sequential organ failure assessment and model for end-stage liver
      disease scores for predicting short term mortality in cirrhotic patients admitted
      to intensive care unit.
AB  - BACKGROUND: Prognostic scores in an intensive care unit (ICU) evaluate outcomes,
      but derive from cohorts containing few cirrhotic patients. AIMS: To evaluate 6
      week mortality in cirrhotic patients admitted to an ICU, and to compare general
      and liver-specific prognostic scores. METHODS: A total of 312 consecutive
      cirrhotic patients (65% alcoholic; mean age 49.6 years). Multivariable logistic
      regression to evaluate admission factors associated with survival. Child-Pugh,
      Model for End-stage Liver Disease (MELD), Acute Physiology and Chronic Health
      Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were
      compared by receiver operating characteristic curves. RESULTS: Major indication
      for admission was respiratory failure (35.6%). Median (range) Child-Pugh, APACHE
      II, MELD and SOFA scores were 11 (5-15), 18 (0-44), 24 (6-40) and 11 (0-21),
      respectively; 65% (n = 203) died. Survival improved over time (P = 0.005).
      Multivariate model factors: more organs failing (FOS) (<3 = 49.5%, > or =3 =
      90%), higher FiO(2), lactate, urea and bilirubin; resulting in good
      discrimination [area under receiver operating characteristic curve (AUC) = 0.83],
      similar to SOFA and MELD (AUC = 0.83 and 0.81, respectively) and superior to
      APACHE II and Child-Pugh (AUC = 0.78 and 0.72, respectively). CONCLUSIONS:
      Cirrhotics admitted to ICU with > or =3 failing organ systems have 90% mortality.
      The Royal Free model discriminated well and contained key variables of organ
      function. SOFA and MELD were better predictors than APACHE II or Child-Pugh
      scores.

PMID- 16573792
TI  - Biliary lipids, cholesterol and bile synthesis: different adaptive mechanisms to
      dietary cholesterol in lean and obese subjects.
AB  - BACKGROUND: Increased biliary cholesterol secretion together with elevated
      cholesterol synthesis may predispose obese subjects to cholesterol gallstone
      formation. AIM: To investigate whether processing of dietary cholesterol is
      altered in obesity, we enrolled eight lean and seven obese subjects in a double
      blind crossover study. METHODS: Cholesterol consumption was 300 mg/day on low and
      1300 mg/day on high cholesterol diet. After 3 weeks on either diet, hepatic bile
      was collected to determine biliary lipid secretion, and bile salt composition by
      high-performance liquid chromatography and cholesterol saturation index was
      calculated. Cholesterol synthesis was measured employing mass isotopomer
      distribution analysis. Bile acid synthesis via neutral and acidic pathway was
      assessed by serum levels of 7alpha-hydroxy-4-cholesten-3-one and 27
      hydroxycholesterol. RESULTS: Cholesterol synthesis was increased in obese
      compared with lean and feedback inhibited only in obese. On low cholesterol diet,
      cholesterol secretion was doubled in obese but bile acid composition and
      synthesis was similar between the two groups. After high cholesterol diet,
      cholesterol saturation index and bile secretion were unchanged. In contrast to
      obese, lean increased bile acid synthesis only via the acidic pathway.
      CONCLUSIONS: Dietary cholesterol appears to preferentially induce bile acid
      synthesis via the acidic pathway in lean, whereas cholesterol synthesis was
      inhibited in obese. Thus, stable cholesterol saturation index may be achieved by
      different mechanisms.

PMID- 16573793
TI  - Circulating ghrelin level is increased in coeliac disease as in functional
      dyspepsia and reverts to normal during gluten-free diet.
AB  - BACKGROUND: It is controversial whether serum ghrelin concentration is altered in
      coeliac disease and whether this alteration is related to nutritional impairment
      or to inflammatory changes of duodenal mucosa. AIM: To investigate clinical and
      histopathological variables affecting circulating ghrelin in coeliac patients by
      comparison with dyspeptic patients and with healthy controls. METHODS: We
      measured serum ghrelin and obtained gastric and duodenal biopsies in 44 coeliac
      patients before and after 1-year gluten-free diet, in 39 dyspeptic patients and
      53 healthy controls. RESULTS: Serum ghrelin concentration was significantly
      higher in coeliac (531 +/- 29 pg/mL, P < 0.05) and in dyspeptic patients (526 +/-
      14 pg/mL, P < 0.01) than in healthy controls (451 +/- 8 pg/mL), and body mass
      index was significantly lower in coeliac (20 +/- 1) and in dyspeptic patients (20
      +/- 1) than in healthy controls (22 +/- 1, P < 0.05). In coeliac patients serum
      ghrelin concentration was not related to the severity of duodenal lesions. Serum
      ghrelin reverted to normal (399 +/- 30 pg/mL) and body mass index increased
      significantly (0.6 +/- 0.1 kg/m(2) increase, P < 0.05) during gluten-free diet
      despite persistent duodenal lymphocytic infiltration. CONCLUSIONS: Ghrelin
      concentration is increased and body mass index is decreased in coeliac and in
      dyspeptic patients irrespective of presence and severity of duodenal
      inflammation. Nutritional impairment is a key factor in elevating plasma ghrelin
      levels in coeliac disease.

PMID- 16573794
TI  - Unawareness of gastrointestinal symptomatology in adult coeliac patients with
      unexplained iron-deficiency anaemia presentation.
AB  - BACKGROUND: Most adults with coeliac disease have a subclinical form of the
      disease and iron-deficiency anaemia may be the sole presenting symptom. AIM: To
      evaluate demographic, clinical and biochemical characteristics of adult coeliac
      disease patients presenting with iron-deficiency anaemia. PATIENTS: A total of
      108 iron-deficiency anaemia patients in whom coeliac disease has been diagnosed
      were studied. As a control group 108 non-coeliac iron-deficiency anaemia
      patients, comparable for sex and age, were studied. RESULTS: Of the 108 coeliac
      disease patients, 95 (88%) were female (mean age 34 years, range 19-72) and 13
      (12%) were male (mean age 33 years, range 15-65). The median duration of iron
      deficiency anaemia before diagnosis was 66 months in coeliac disease patients and
      14 months in the iron-deficiency anaemia control group (P = 0.0001). The
      occurrence of at least one gastrointestinal symptom, not spontaneously reported,
      was observed in 92 (85%) patients with coeliac disease and in 67 (62%) patients
      in the control group (P = 0.001). The concomitant presence of diarrhoea,
      abdominal pain and abdominal bloating was detected in 14% patients with coeliac
      disease with respect to 3% in the control group (P = 0.005). CONCLUSIONS: The
      vast majority of coeliac disease patients with iron-deficiency anaemia
      presentation were unaware of the gastrointestinal symptoms and this relationship
      is useful for diet compliance.

PMID- 16573795
TI  - Predictors of the placebo response in functional dyspepsia.
AB  - BACKGROUND: Trials in functional dyspepsia report placebo response rates of 30%
      to 40%. AIM: We aimed to identify predictors of the placebo response. METHODS:
      Patients from primary, secondary and tertiary practices with functional dyspepsia
      defined by Rome II criteria were enrolled into one of four clinical trials; 220
      patients were randomized to receive placebo. Scintigraphic assessment of gastric
      emptying at baseline was repeated at the end of the treatment in those with
      delayed emptying. After a 2 week run-in period, patients were followed for 8
      weeks on placebo. Response was assessed on a weekly basis and a responder was
      defined as satisfactory relief of meal-related symptoms on at least 50% of weeks.
      RESULTS: The mean age was 44 years (range 18-82) and 74% were female; 76 (35%)
      were placebo responders. The predominant symptom was an unstable measure over the
      trial. Independent predictors of a lower placebo response were lower body mass
      index and a more consistent predominant symptom pattern (both P < 0.05). No
      association was seen with age, gender, centre type, baseline symptom score,
      baseline or change in gastric emptying, or baseline quality of life. CONCLUSION:
      In functional dyspepsia, a consistent predominant symptom pattern and lower body
      mass index may be associated with a lower placebo response rate.

PMID- 16573796
TI  - Increased use of selective serotonin reuptake inhibitors in patients admitted
      with gastrointestinal haemorrhage: a multicentre retrospective analysis.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) can adversely affect
      platelet function and impair haemostasis. Various bleeding complications have
      been reported in persons taking SSRIs including an increased risk of
      gastrointestinal haemorrhage (GIH). AIM: To evaluate SSRI use in patients
      hospitalized with GIH compared with controls. METHODS: A retrospective,
      multicentre case-control study determined use of SSRIs, non-steroidal anti
      inflammatory drugs (NSAIDs), aspirin, clopidogrel, coumadin and enoxaparin in
      patients admitted with GIH and age- and sex-matched controls. Exclusion criteria
      included liver disease, portal hypertension or bleeding diathesis. RESULTS: A
      total of 579 cases were matched with 1000 controls. SSRI use was 19.2% in cases
      and 13.6% in controls [OR (95% CI) = 1.5 (1.2-2.0); P = 0.003]. NSAIDs were used
      by 7.3% of cases and 3.8% of controls [OR = 2.0 (1.3-3.1); P = 0.003]. SSRI use
      was more strongly associated with lower [1.8 (1.2-2.8)] rather than upper [1.3
      (0.83-1.9)] GIH. Significant interactions existed for SSRI use with NSAIDs and
      aspirin. CONCLUSIONS: Patients admitted with GIH gastrointestinal bleeding were
      more likely to be taking SSRIs than controls. This association exists for lower
      as well as upper GIH. Physicians should be aware of this risk particularly in
      patients already using medications that increase GIH risk.

PMID- 16573797
TI  - Extended flexible sigmoidoscopy performed by colonoscopists for colorectal cancer
      screening: a pilot study.
AB  - BACKGROUND: Caecal intubation can be achieved by extended flexible sigmoidoscopy
      in 32% of patients. AIM: To assess the feasibility of extended flexible
      sigmoidoscopy performed by colonoscopists for colorectal cancer screening.
      METHODS: We enrolled 41 patients referred for screening flexible sigmoidoscopy.
      After purging, examination was performed with a colonoscope. All patients
      completed sigmoidoscopy (success in meeting referral goal); 93% and 71% had
      examination to the transverse or ascending colon, and caecum, respectively.
      Overall yield and right-sided polyps was 56% and 27%, respectively. Caecal
      intubation and complete examination with polypectomy took 6.0 +/- 2.5 and 18.3 +/
      5.1 min, respectively; with no complications. Twelve patients requested
      colonoscope withdrawal because of discomfort. Although 46% reported moderate to
      severe discomfort, 39% and 36%, respectively, were definitely or probably willing
      to repeat flexible sigmoidoscopy. RESULTS: Unsedated colonoscopy introduced as
      extended flexible sigmoidoscopy emphasizes the benefits of added yield rather
      than the negative image of withholding of discomfort relief. The patient can
      choose to accept the equivalent of an unsedated colonoscopy or reject the option
      based on perceived discomfort during extended flexible sigmoidoscopy performed by
      the colonoscopist. CONCLUSION: Extended flexible sigmoidoscopy is a feasible
      option in carefully selected patients, fully prepared and by an experienced
      colonoscopist.

PMID- 16573798
TI  - Gastroenterologists utilize the referral for EGD to enhance colon cancer
      screening more effectively than primary care physicians.
AB  - BACKGROUND: Colorectal cancer screening rates among patients with upper
      gastrointestinal symptoms undergoing oesophagogastroduodenoscopy have not been
      previously established. We hypothesize that gastroenterologists seize this
      opportunity more frequently than primary care providers. AIMS: To assess
      colorectal cancer screening rates at the time of direct access
      oesophagogastroduodenoscopy and gastrointestinal clinic evaluation for upper
      gastrointestinal symptoms. To compare rates in the 6 months following the
      oesophagogastroduodenoscopy in both cohorts of patients. METHODS: Retrospective
      review. primary care physician group: direct access oesophagogastroduodenoscopy
      (n = 247) vs. gastrointestinal group (n = 278). Multivariable regression analysis
      utilized to assess predictors of screening outcome. RESULTS: Colorectal cancer
      screening at the time of referral was 54%. Among the 243 unscreened patients, an
      additional 29% in the primary care physician group vs. 59% in the
      gastrointestinal group completed colorectal cancer screening in 6 months of
      follow-up. Nearly 60% patients evaluated in gastrointestinal clinic for upper
      symptoms had documented discussion, and 99% of those patients underwent
      colonoscopy (P < 0.001). Gastrointestinal consultation increased the probability
      of colorectal cancer screening completion eightfold (95% CI 3.69-18.96).
      CONCLUSIONS: At the time of evaluation for upper symptoms, half of patients were
      not current with colorectal cancer screening recommendations. Referrals for the
      direct access oesophagogastroduodenoscopy and, more importantly, the
      gastroenterology consult represent key opportunities for colorectal cancer
      screening education and improved compliance.

PMID- 16573799
TI  - Effect of lactulose and Saccharomyces boulardii administration on the colonic
      urea-nitrogen metabolism and the bifidobacteria concentration in healthy human
      subjects.
AB  - BACKGROUND: Protein fermentation products, especially ammonia, are implicated in
      the pathogenesis of certain diseases. AIM: To investigate the influence of
      lactulose and Saccharomyces boulardii cells on the composition of the intestinal
      microbiota and on the metabolic fate of ammonia by means of lactose-[(15)N,
      (15)N]-ureide. METHODS: An at random, placebo-controlled, crossover study was
      performed in 43 healthy volunteers to evaluate the influence of lactulose and/or
      S. boulardii cells either administered as a single dose or after a 4-week intake
      period. Urine and faeces were collected. All samples were analysed for (15)N
      content by combustion-isotope ratio mass spectrometry. Real-time polymerase chain
      reaction was applied to determine the composition of the predominant faecal
      microbiota. RESULTS: A single administration of lactulose significantly decreased
      urinary (15)N-excretion in a dose-dependent way. After long-term administration
      of lactulose, a significant reduction of the urinary (15)N-excretion was
      observed, which was accompanied with a significant increase in the faecal (15)N
      output, more specifically more (15)N was found in the bacterial fraction. A
      significant rise in the Bifidobacterium population was found after lactulose
      intake. No significant effects were observed after S. boulardii intake.
      CONCLUSION: Dietary addition of lactulose can exert a bifidogenic effect
      accompanied by a favourable effect on the colonic NH(3)-metabolism.

PMID- 16573800
TI  - Dose-response evaluation of the antisecretory effect of continuous infusion
      intravenous lansoprazole regimens over 48 h.
AB  - BACKGROUND: Attainment of intragastric pH < 6.0 may require high-dose
      continuously infused proton pump therapy. AIM: To assess the pharmacokinetic and
      pharmacodynamic dose-responses of continuous infusion regimens of lansoprazole.
      METHODS: Healthy adult subjects were assigned to lansoprazole 60-mg intravenous
      bolus, followed by 6-mg/h continuous infusion; a 90-mg intravenous bolus followed
      by 6-, 7.5-, or 9-mg/h continuous infusion; or placebo. RESULTS: Mean
      intragastric pH values for lansoprazole regimens ranged from 4.8 to 5.2 (0-24 h),
      5.5 to 6.0 (>24 to 48 h) and 5.2 to 5.6 (0-48 h). Within these three intervals,
      the percentages of time intragastric pH exceeded 4, 5 and 6 ranged from 65% to
      96%, 54% to 88% and 30% to 61% respectively. Pharmacokinetic parameters were dose
      independent with steady-state plasma concentrations achieved within 6-12 h
      postdose and maintained over 48 h. The mean systemic clearance of lansoprazole
      was lower in CYP2C19 heterozygous metabolizers than in homozygous extensive
      metabolizers (9.2 vs. 16.5 L/h), with substantial variability resulting in
      overlapping ranges of clearance values for both subpopulations. All lansoprazole
      regimens were well-tolerated. CONCLUSIONS: Lansoprazole administered as a 60-mg
      intravenous bolus followed by 6-mg/h continuous infusion produced intragastric pH
      effects comparable with those of higher dosage regimens.

PMID- 16573801
TI  - Lansoprazole regimens that sustain intragastric pH > 6.0: an evaluation of
      intermittent oral and continuous intravenous infusion dosages.
AB  - BACKGROUND: Orally and intravenously administered proton pump inhibitors have
      been shown to reduce rebleeding rates, surgery and transfusion requirement. AIM:
      To compare lansoprazole intravenous and orally disintegrating tablet (Prevacid
      SoluTab) regimens with a pantoprazole intravenously administered regimen in
      sustaining intragastric pH >6.0. METHODS: Two similarly designed three-way,
      randomized crossover studies each enrolled 36 Helicobacter pylori-negative
      healthy volunteers. Study 1 regimens included intravenously administered bolus
      followed by 24-h continuous infusion (lansoprazole 90 mg, 6 mg/h; lansoprazole
      120 mg, 6 mg/h; pantoprazole 80 mg, 8 mg/h). Study 2 regimens included
      intravenous bolus followed by lansoprazole orally disintegrating tablet or
      intravenous continuous infusion for 24 h (lansoprazole 90 mg, lansoprazole orally
      disintegrating tablet 60 mg every 6 h; lansoprazole 120 mg, 9 mg/h; pantoprazole
      80 mg, 8 mg/h). Percentage of time pH >6.0 was assessed with 24-h intragastric pH
      monitoring. RESULTS: All regimens produced comparable gastric acid suppression.
      In both studies, regimens superior to pantoprazole included lansoprazole 90 mg, 6
      mg/h; lansoprazole 90 mg, lansoprazole orally disintegrating tablet 60 mg q.d.s.
      and lansoprazole 120 mg, 9 mg/h (P < or = 0.013). The lansoprazole 120-mg, 6-mg/h
      regimen (P = 0.082) was not superior to pantoprazole in percentage of time
      intragastric pH >6.0. Mild reaction at the intravenous injection site was the
      most frequently reported adverse event. CONCLUSIONS: The intravenous bolus and
      continuously infused lansoprazole or intravenous bolus and intermittent
      lansoprazole orally disintegrating tablet regimens are as effective as
      intravenous pantoprazole in sustaining intragastric pH >6.0.

PMID- 16573802
TI  - The effects of esomeprazole combined with aspirin or rofecoxib on prostaglandin
      E2 production in patients with Barrett's oesophagus.
AB  - BACKGROUND: Reducing mucosal cyclo-oxygenase-2 and prostaglandin E(2) production
      and suppressing intraoesophageal acid may be effective chemopreventive strategies
      in patients with Barrett's oesophagus. AIM: To compare the effects of aspirin and
      rofecoxib when administered with esomeprazole on prostaglandin E(2) production,
      cyclo-oxygenase-2 expression and proliferating cell nuclear antigen expression in
      patients with Barrett's oesophagus. METHODS: This exploratory, multicentre,
      randomized, open-label, four-way crossover study in 45 patients with Barrett's
      oesophagus evaluated prostaglandin E(2) content, proliferating cell nuclear
      antigen expression, and cyclo-oxygenase-2 expression after 10 days of sequential
      treatments with: esomeprazole 40 mg twice daily plus aspirin 325 mg once daily
      (E40 b.d. + A325); E40 b.d. plus rofecoxib 25 mg once daily (E40 b.d. + R25); E40
      b.d.; and rofecoxib 25 mg once daily (R25). RESULTS: Prostaglandin E(2) content
      reduction in Barrett's oesophagus tissue was significantly greater with E40 b.d.
      + A325 compared with E40 b.d. + R25, E40 b.d. or R25 (P < 0.05). All treatments
      containing E40 b.d. significantly decreased proliferating cell nuclear antigen
      expression from baseline (P < 0.05). None of the treatments significantly reduced
      cyclo-oxygenase-2 expression. CONCLUSIONS: The combined treatment of esomeprazole
      40 mg b.d. and aspirin 325 mg significantly decreased mucosal prostaglandin E(2)
      content and all treatments containing esomeprazole significantly reduced
      proliferating cell nuclear antigen expression in patients with Barrett's
      oesophagus.

PMID- 16573803
TI  - Altered levels of biochemical indices of bone turnover and bone-related vitamins
      in patients with Crohn's disease and ulcerative colitis.
AB  - BACKGROUND: The pathogenesis of inflammatory bowel disease-associated osteopenia
      may be related to pathological rates of bone turnover; however, the literature
      shows mixed results. AIM: To compare bone biomarkers in inflammatory bowel
      disease patients (Crohn's disease: n = 68, and ulcerative colitis: n = 32,
      separately) with age- and sex-matched healthy controls. SUBJECTS: Patients and
      controls were recruited from Cork University Hospital and Cork City area,
      respectively. RESULTS: Relative to that in their respective controls, Crohn's
      disease (n = 47) and ulcerative colitis (n = 26) patients (i.e. excluding
      supplement users) had significantly (P < 0.05-0.001) higher serum
      undercarboxylated osteocalcin (by 27% and 63%, respectively) and bone-specific
      alkaline phosphatase (by 15% and 21%, respectively) and urinary Type I collagen
      cross-linked N-telopeptides concentrations (by 87% and 112%, respectively).
      Relative to that in their respective controls, Crohn's disease and ulcerative
      colitis patients had significantly (P < 0.01) lower serum total osteocalcin (by
      20% and 42%, respectively) and 25-hydroxyvitamin D (by 37% and 42%,
      respectively), while serum parathyroid hormone levels were similar. In the
      combined patient group (n = 100), undercarboxylated osteocalcin was positively
      associated with bone markers. CONCLUSIONS: Both Crohn's disease and ulcerative
      colitis patients have altered bone turnover relative to that in healthy controls.

PMID- 16573806
TI  - The association of body mass index with Barrett's oesophagus.

PMID- 16573804
TI  - Comparison of the efficacy and safety of Eudragit-L-coated mesalazine tablets
      with ethylcellulose-coated mesalazine tablets in patients with mild to moderately
      active ulcerative colitis.
AB  - BACKGROUND: There are no comparative studies of coated mesalazine. AIM: To
      compare the efficacy and tolerability of Eudragit-L- and ethylcellulose-coated
      mesalazine tablets in patients with mild to moderately active ulcerative colitis.
      METHODS: A double-blind, double-dummy, randomized parallel group trial was
      performed across 18 centres in Australia, and 20 in Eastern Europe. Patients were
      treated with 3 g mesalazine for 8 weeks with the primary efficacy end point being
      clinical remission. RESULTS: Of 215 patients, 69% achieved clinical remission in
      both treatment groups (P < 0.001; chi-square test) with no differences in
      frequency of adverse events. In the Australian cohort (n = 63), the Eudragit-L
      group had a higher remission rate (73% vs. 36%) and responded 13 days faster,
      compared with those in the European group (67% vs. 84%, and 2 days respectively).
      No clear reasons for differences in treatment responses were identified.
      CONCLUSIONS: Eudragit-L and ethylcellulose-coated mesalazine tablets are well
      tolerated and equally effective in achieving remission in mild-moderately active
      ulcerative colitis over 8 weeks.

PMID- 16573808
TI  - A two-stage approach for improved prediction of residue contact maps.
AB  - BACKGROUND: Protein topology representations such as residue contact maps are an
      important intermediate step towards ab initio prediction of protein structure.
      Although improvements have occurred over the last years, the problem of
      accurately predicting residue contact maps from primary sequences is still
      largely unsolved. Among the reasons for this are the unbalanced nature of the
      problem (with far fewer examples of contacts than non-contacts), the formidable
      challenge of capturing long-range interactions in the maps, the intrinsic
      difficulty of mapping one-dimensional input sequences into two-dimensional output
      maps. In order to alleviate these problems and achieve improved contact map
      predictions, in this paper we split the task into two stages: the prediction of a
      map's principal eigenvector (PE) from the primary sequence; the reconstruction of
      the contact map from the PE and primary sequence. Predicting the PE from the
      primary sequence consists in mapping a vector into a vector. This task is less
      complex than mapping vectors directly into two-dimensional matrices since the
      size of the problem is drastically reduced and so is the scale length of
      interactions that need to be learned. RESULTS: We develop architectures composed
      of ensembles of two-layered bidirectional recurrent neural networks to classify
      the components of the PE in 2, 3 and 4 classes from protein primary sequence,
      predicted secondary structure, and hydrophobicity interaction scales. Our
      predictor, tested on a non redundant set of 2171 proteins, achieves
      classification performances of up to 72.6%, 16% above a base-line statistical
      predictor. We design a system for the prediction of contact maps from the
      predicted PE. Our results show that predicting maps through the PE yields
      sizeable gains especially for long-range contacts which are particularly critical
      for accurate protein 3D reconstruction. The final predictor's accuracy on a non
      redundant set of 327 targets is 35.4% and 19.8% for minimum contact separations
      of 12 and 24, respectively, when the top length/5 contacts are selected. On the
      11 CASP6 Novel Fold targets we achieve similar accuracies (36.5% and 19.7%). This
      favourably compares with the best automated predictors at CASP6. CONCLUSION: Our
      final system for contact map prediction achieves state-of-the-art performances,
      and may provide valuable constraints for improved ab initio prediction of protein
      structures. A suite of predictors of structural features, including the PE, and
      PE-based contact maps, is available at http://distill.ucd.ie.

PMID- 16573809
TI  - The use of whole genome amplification to study chromosomal changes in prostate
      cancer: insights into genome-wide signature of preneoplasia associated with
      cancer progression.
AB  - BACKGROUND: Prostate cancer (CaP) is a disease with multifactorial etiology that
      includes both genetic and environmental components. The knowledge of the genetic
      basis of CaP has increased over the past years, mainly in the pathways that
      underlie tumourigenesis, progression and drug resistance. The vast majority of
      cases of CaP are adenocarcinomas that likely develop through a pre-malignant
      lesion and high-grade prostatic intraepithelial neoplasia (HPIN). Histologically,
      CaP is a heterogeneous disease consisting of multiple, discrete foci of invasive
      carcinoma and HPIN that are commonly interspersed with benign glands and stroma.
      This admixture with benign tissue can complicate genomic analyses in CaP.
      Specifically, when DNA is bulk-extracted the genetic information obtained
      represents an average for all of the cells within the sample. RESULTS: To
      minimize this problem, we obtained DNA from individual foci of HPIN and CaP by
      laser capture microdissection (LCM). The small quantities of DNA thus obtained
      were then amplified by means of multiple-displacement amplification (MDA), for
      use in genomic DNA array comparative genomic hybridisation (gaCGH). Recurrent
      chromosome copy number abnormalities (CNAs) were observed in both HPIN and CaP.
      In HPIN, chromosomal imbalances involving chromosome 8 where common, whilst in
      CaP additional chromosomal changes involving chromosomes 6, 10, 13 and 16 where
      also frequently observed. CONCLUSION: An overall increase in chromosomal changes
      was seen in CaP compared to HPIN, suggesting a universal breakdown in chromosomal
      stability. The accumulation of CNAs, which occurs during this process is non
      random and may indicate chromosomal regions important in tumourigenesis. It is
      therefore likely that the alterations in copy number are part of a programmed
      cycle of events that promote tumour development, progression and survival. The
      combination of LCM, MDA and gaCGH is ideally suited for the identification of
      CNAs from small cell clusters and may assist in the discovery of potential
      genomic markers for early diagnosis, or identify the location of tumour
      suppressor genes (TSG) or oncogenes previously unreported in HPIN and CaP.

PMID- 16573810
TI  - Stage-variations of anandamide hydrolase activity in the mouse uterus during the
      natural oestrus cycle.
AB  - Recent studies have demonstrated that the endogenous cannabinoids are important
      modulators of fertility in mammals. In particular, a role of the endocannabinoid
      system in early stages of embryo development, oviductal transport of embryos,
      pregnancy maintenance and labour has been demonstrated in rodents and/or in
      humans. In the present paper, we report the analysis of FAAH activity and protein
      content in the mouse uterus as a function of the natural oestrus cycle stages.
      Variations of FAAH activity are discussed in relationship to changes in sex
      steroid levels and to the possible action of AEA on remodelling of uterine
      tissues.

PMID- 16573811
TI  - The Glu27 genotypes of the beta2-adrenergic receptor are predictors for severe
      coronary artery disease.
AB  - BACKGROUND: The role of the Beta2-adrenoceptor (beta2-AR) Gln27Glu polymorphism
      in the manifestation of cardiovascular diseases is still unclear. METHODS: In the
      present study, we evaluated the potential relevance of the c.79 C>G (p.Gln27Glu)
      polymorphism of this receptor gene for coronary artery disease (CAD) and its
      associated risk factors in Saudi Arabs. Genotyping was performed by PCR using the
      confronting two-pair primer (PCR-CTPP) method. RESULTS: In the general population
      group (BD) (n = 895), 68.5% were homozygous wild-type C/C, 28.3% were
      heterozygous C/G and 3.2% were homozygous mutant G/G. Among the CAD patients (n =
      773), 50.6% were homozygous wild-type C/C, 43.6% were heterozygous C/G and 5.8%
      were homozygous mutant G/G, while in the angiographed control group (CON) (n =
      528), 71.8% were C/C, 24.4% C/G and 3.8% G/G genotypes. These results indicate
      that both the C/G (p = or < .001) and G/G (p = .005) genotypes are significantly
      associated with CAD, when compared to the CON group. In addition, C/G (p = or <
      .001) and G/G (p = or < .001) were significantly associated with CAD, when
      compared to the BD group. Furthermore, stepwise logistic regression showed that
      the genotype [C/G (p < .001) and G/G (p < .001)] increase the risk of CAD.
      CONCLUSION: These results shows that the Gln27Glu genotypes (homo- or
      heterozygous) of the beta2-AR may be independent predictors of severe CAD.

PMID- 16573812
TI  - Detection of divergent genes in microbial aCGH experiments.
AB  - BACKGROUND: Array-based comparative genome hybridization (aCGH) is a tool for
      rapid comparison of genomes from different bacterial strains. The purpose of such
      analysis is to detect highly divergent or absent genes in a sample strain
      compared to an index strain. Development of methods for analyzing aCGH data has
      primarily focused on copy number abberations in cancer research. In microbial
      aCGH analyses, genes are typically ranked by log-ratios, and classification into
      divergent or present is done by choosing a cutoff log-ratio, either manually or
      by statistics calculated from the log-ratio distribution. As experimental
      settings vary considerably, it is not possible to develop a classical
      discriminant or statistical learning approach. METHODS: We introduce a more
      efficient method for analyzing microbial aCGH data using a finite mixture model
      and a data rotation scheme. Using the average posterior probabilities from the
      model fitted to log-ratios before and after rotation, we get a score for each
      gene, and demonstrate its advantages for ranking and detecting divergent genes
      with enlarged specificity and sensitivity. RESULTS: The procedure is tested and
      compared to other approaches on simulated data sets, as well as on four
      experimental validation data sets for aCGH analysis on fully sequenced strains of
      Staphylococcus aureus and Streptococcus pneumoniae. CONCLUSION: When tested on
      simulated data as well as on four different experimental validation data sets
      from experiments with only fully sequenced strains, our procedure out-competes
      the standard procedures of using a simple log-ratio cutoff for classification
      into present and divergent genes.

PMID- 16573814
TI  - Aspergillosis with pulmonary echinococcosis.

PMID- 16573813
TI  - Sensitivity as outcome measure of androgen replacement: the AMS scale.
AB  - BACKGROUND: The capacity of the AMS scale as clinical utility and as outcome
      measure still needs validation. METHODS: An open post-marketing study was
      performed by office-based physicians in Germany in 2004. We analysed data of 1670
      androgen-deficient males who were treated with testosterone gel. The AMS scale
      was applied prior to and after 3 months treatment. RESULTS: The improvement of
      complaints under treatment relative to the baseline score was 30.7% (total
      score), 27.3% (psychological domain), 30.5% (somatic domain), and 30.7% (sexual
      domain), respectively. Patients with little or no symptoms before therapy
      improved by 9%, those with mild complaints at entry by 24%, with moderate by 32%,
      and with severe symptoms by 39% - compared with the baseline score. We showed
      that the distribution of complaints of testosterone deficient men before therapy
      almost returned to norm values after 12 weeks of testosterone treatment. Age,
      BMI, and total testosterone level at baseline did not modify the positive effect
      of androgen therapy. We also demonstrated that the AMS results can predict the
      independent (physician's) opinion about the individual treatment effect. Both,
      sensitivity (correct prediction of a positive assessment by the physician) and
      specificity (correct prediction of a negative assessment by the physician) were
      over 70%, if about 22% improvement of the AMS total score was used as cut-off
      point. CONCLUSION: The AMS scale showed a convincing ability to measure treatment
      effects on quality of life across the full range of severity of complaints.
      Effect modification by other variables at baseline was not observed. In addition,
      results of the scale can predict the subjective clinical expert opinion on the
      treatment efficiency.

PMID- 16573815
TI  - Farmers' perception on the importance of variegated grasshopper (Zonocerus
      variegatus (L.)) in the agricultural production systems of the humid forest zone
      of Southern Cameroon.
AB  - BACKGROUND: Zonocerus variegatus (Linnaeus, 1758) (Orthoptera: Pyrgomorphidae) is
      known as an agricultural pest in West and Central Africa. However, its importance
      in the agricultural production system in Cameroon has not been investigated. The
      study assesses farmers' perception on the importance of Z. variegatus in the
      agricultural production systems of the humid forest zone of Southern Cameroon.
      METHODS: Research was carried out in 5 villages of each of three Agro-Ecological,
      Cultural and Demographic Blocks (AECD-Blocks) of the Forest Margin Benchmark Area
      (FMBA). In each village, a semi-structured survey was used; male and female
      groups of farmers were interviewed separately. RESULTS: Z. variegatus is present
      throughout the humid forest zone of Southern Cameroon, where it is ranked as the
      third most economically important insect pest of agriculture. In the farmers'
      opinion, Z. variegatus is a polyphagous insect with little impact on young
      perennial crops. The length of the pre-farming fallow does not affect Z.
      variegatus pest pressure in the following crops. The increased impact of the
      grasshopper observed today in the fields, compared to what existed 10 years ago
      is as a result of deforestation and increase in surface of herbaceous fallow. The
      damage caused by Z. variegatus is higher in fields adjacent to C. odorata and
      herbaceous fallows than in those adjacent to forests and shrubby fallows. The
      fight against this grasshopper is often done through physical methods carried out
      by hand, for human consumption. The farmers highlight low usage of the chemical
      methods and a total absence of biological and ecological methods. CONCLUSION:
      Farmers' perception have contributed to understanding the status of Z. variegatus
      in the humid forest zone of Southern Cameroon. The results are in general similar
      to those obtained in other countries.

PMID- 16573816
TI  - Cerebrovascular disease associated with antiphospholipid antibodies: more
      questions than answers.
AB  - Neurological syndromes occur in a significant number of patients with
      antiphospholipid antibodies. The optimal management for these patients however
      remains uncertain. Our study is a descriptive analysis looking retrospectively at
      45 patients who presented to the principal tertiary referral centre in the
      Australian Capital Territory, with either cerebral arterial or venous thrombosis
      for which there was no obvious cause for their presentation when initially
      reviewed. The diagnosis was based on the clinical findings made by one of three
      neurologists attached to our centre. Radiological findings and the presence of
      either IgM or IgG anticardiolipin antibodies, IgG anti-beta-2 glycoprotein 1
      antibodies or a lupus anticoagulant were then documented. In this group of
      patients three subgroups were identified:1. Individuals that fulfilled the
      Sapporo Classification Criteria2. Individuals with transiently positive
      antiphospholipid antibodies and3. Individuals with persistently low positive
      antiphospholipid antibodies. The most interesting of these three groups are those
      individuals with transiently positive antiphospholipid antibodies. A potential
      cause for presentation was identified in only one patient of this group with
      documented infective endocarditis and bacteraemia. Comparison with the other two
      groups suggested that there was little in terms of clinical presentation,
      radiological findings or intercurrent risk factors for thrombotic disease to
      distinguish between them. With disappearance of antiphospholipid antibodies, the
      individuals within this group have not had further thrombotic events. Our
      observations emphasise the problems that continue to exist in relation to the
      occurrence of cerebrovascular disease in the context of antiphospholipid
      antibodies and the optimal management of these stratified groups. Our findings
      also raise an as yet unanswered question as to the signficance of these
      transiently positive antiphospholipid antibodies. In the absence of significant
      intercurrent risk factors our findings would suggest that in the group we
      describe that they are likely to be of clinical significance.

PMID- 16573817
TI  - Upper airway dynamics during negative expiratory pressure in apneic and non
      apneic awake snorers.
AB  - BACKGROUND: The ability of negative expiratory pressure (NEP) technique to
      differentiate between awake snorers with and without obstructive sleep apnea
      hypopnea (OSAH) was investigated. METHODS: Forty-eight subjects with sleep
      disordered breathing (SDB) and 7 healthy subjects, as non-snorer controls,
      underwent the NEP application of -5 and -7 cmH2O in the seated and supine
      position during wakefulness, after performing a sleep study. The upper airway
      collapsibility was assessed by computing the volume exhaled during the first 0.5
      sec. (V,NEP0.5) and 1 sec. (V,NEP1) following the NEP start. RESULTS: Patients
      with severe (AHI > or = 30) (n = 19) and mild-to-moderate (AHI <30 and >5) (n =
      15) OSAH had lower V,NEP0.5 (340 +/- 88 ml) as compared to snorers (AHI < or = 5)
      (n = 14) (427 +/- 101 ml; p < 0.01) and controls (n = 7) (492 +/- 69 ml; p <
      0.001) in the supine position with NEP -5 cmH2O. Less significant differences
      among the different groups were observed for V,NEP0.5 in the seated position with
      NEP -5 cmH2O and in both positions with NEP -7 cmH2O (only OSAH patients vs
      controls, p < 0.001). Similar results were obtained for V,NEP1 in either position
      by using both NEP -5 cmH2O and -7 cmH2O. In spite of this, a substantial
      overlapping of V,NEP0.5 and V,NEP1 between snorers and OSAH patients did not
      allow to identify a reliable diagnostic cut-off level. An inverse correlation
      with AHI was found for V,NEP0.5 in the supine position with NEP -5 cmH2O (rs = 
      0.46, p < 0.05) in severe OSAH patients. CONCLUSION: The awake OSAH patients
      exhibit values of V,NEP0.5 and V,NEP1 lesser than those of awake snorers. The NEP
      technique, however, appears to have a limited usefulness as clinical tool for
      routine screening of the OSAH patients during wakefulness.

PMID- 16573818
TI  - Perforated gastric carcinoma: a report of 10 cases and review of the literature.
AB  - BACKGROUND: Perforation is a rare complication of gastric carcinoma, accounting
      for less than 1% of all gastric cancer cases. The aim of the present study is to
      evaluate the prognostic value of perforation and to point out the surgical
      treatment options. METHODS: A total of 10 patients with perforated gastric
      carcinoma were retrospectively reviewed among 2564 consecutive cases of gastric
      cancer operated in three Centers belonging to the Italian Research Group for
      Gastric Cancer. The clinicopathological features including tumor stage and
      survival were analyzed and compared to literature data. RESULTS: Incidence rate
      was 0.39%. All patients underwent emergency surgery, being performed gastrectomy
      in 6 patients (mortality 17%) and repair surgery in 4 patients (mortality 75%).
      The survival of patients was related to the stage of the disease, with 2 long
      survival cases. CONCLUSION: Perforation usually occurs in advanced stages of
      gastric cancer; nevertheless surgeons should not be always discouraged from a
      radical treatment of perforated gastric cancer, since perforation even occurs in
      early stages and seems not to be a negative prognostic factor itself. When
      possible, emergency gastrectomy should be performed, leaving repair surgery for
      unresectable tumors. A two-stage treatment is a good treatment option for frail
      patients with resectable tumors.

PMID- 16573819
TI  - The feasibility and utility of grocery receipt analyses for dietary assessment.
AB  - OBJECTIVE: To establish the feasibility and utility of a simple data collection
      methodology for dietary assessment. DESIGN: Using a cross-sectional design,
      trained data collectors approached adults (approximately 20 - 40 years of age) at
      local grocery stores and asked whether they would volunteer their grocery
      receipts and answer a few questions for a small stipend (dollar 1). METHODS: The
      grocery data were divided into 3 categories: "fats, oils, and sweets," "processed
      foods," and "low-fat/low-calorie substitutions" as a percentage of the total food
      purchase price. The questions assessed the shopper's general eating habits (eg,
      fast-food consumption) and a few demographic characteristics and health aspects
      (eg, perception of body size). Statistical Analyses Performed. Descriptive and
      analytic analyses using non-parametric tests were conducted in SAS. RESULTS:
      Forty-eight receipts and questionnaires were collected. Nearly every respondent
      reported eating fast food at least once per month; 27% ate out once or twice a
      day. Frequency of fast-food consumption was positively related to perceived body
      size of the respondent (p = 0.02). Overall, 30% of the food purchase price was
      for fats, oils, sweets, 10% was for processed foods, and almost 6% was for low
      fat/low-calorie substitutions. Households where no one was perceived to be
      overweight spent a smaller proportion of their food budget on fats, oils, and
      sweets than did households where at least one person was perceived to be
      overweight (p = 0.10); household where the spouse was not perceived to be
      overweight spent less on fats, oils, and sweets (p = 0.02) and more on low
      fat/low-calorie substitutions (p = 0.09) than did households where the spouse was
      perceived to be overweight; and, respondents who perceived themselves to be
      overweight spent more on processed foods than did respondents who did not
      perceive themselves to be overweight (p = 0.06). CONCLUSION: This simple dietary
      assessment method, although global in nature, may be a useful indicator of
      dietary practices as evidenced by its association with perceived weight status.

PMID- 16573820
TI  - Protocol for the Arterial Revascularisation Trial (ART). A randomised trial to
      compare survival following bilateral versus single internal mammary grafting in
      coronary revascularisation [ISRCTN46552265].
AB  - BACKGROUND: Standard coronary artery bypass graft surgery uses a single internal
      mammary artery and supplemental vein or radial artery grafts. Several
      observational studies have suggested a survival benefit with two internal mammary
      artery grafts compared to a single internal mammary artery graft, but this has
      not been tested in a randomised trial. The Arterial Revascularisation Trial is a
      Medical Research Council and British Heart Foundation funded, multi-centre
      international trial comparing single internal mammary artery grafting versus
      bilateral internal mammary artery grafting. METHODS/DESIGN: Twenty centres in the
      UK, Australia, Poland and Brazil are planning to randomise 3000 coronary artery
      bypass graft surgery patients to single or bilateral internal mammary artery
      grafting. Supplemental grafts may be either saphenous vein or radial artery.
      Coronary artery bypass grafting can be performed as an on-pump or off-pump
      procedure. The primary outcome is survival at 10 years and secondary end-points
      include clinical events, quality of life and cost effectiveness. The effect of
      age, left ventricular function, diabetes, number of grafts, vein grafts and off
      pump surgery are pre-specified subgroups. DISCUSSION: The Arterial
      Revascularisation Trial is one of the first randomised trials to evaluate the
      effects on survival and other clinical outcomes of single internal mammary artery
      grafting versus bilateral internal mammary artery grafting, and will help to
      establish the best approach for patients requiring coronary artery bypass graft
      surgery.

PMID- 16573821
TI  - Scaling up health interventions in resource-poor countries: what role does
      research in stated-preference framework play?
AB  - Despite improved supply of health care services in low-income countries in the
      recent past, their uptake continues to be lower than anticipated. This has made
      it difficult to scale-up those interventions which are not only cost-effective
      from supply perspectives but that might have substantial impacts on improving the
      health status of these countries. Understanding demand-side barriers is therefore
      critically important. With the help of a case study from Nepal, this commentary
      argues that more research on demand-side barriers needs to be carried out and
      that the stated-preference (SP) approach to such research might be helpful. Since
      SP techniques place service users' preferences at the centre of the analysis, and
      because preferences reflect individual or social welfare, SP techniques are
      likely to be helpful in devising policies to increase social welfare (e.g.
      improved service coverage). Moreover, the SP data are collected in a controlled
      environment which allows straightforward identification of effects (e.g. that of
      process attributes of care) and large quantities of relevant data can be
      collected at moderate cost. In addition to providing insights into current
      preferences, SP data also provide insights into how preferences are likely to
      respond to a proposed change in resource allocation (e.g. changing service
      delivery strategy). Finally, the SP-based techniques have been used widely in
      resource-rich countries and their experience can be valuable in conducting
      scaling-up research in low-income countries.

PMID- 16573823
TI  - Action of Lovastatin (Mevinolin) on an in vitro model of angiogenesis and its co
      culture with malignant melanoma cell lines.
AB  - BACKGROUND: Lovastatin and other statins may reduce the development of melanomas.
      The effects on melanoma cells and their ability to enhance angiogenesis in a co
      culture system presented an opportunity to assess whether Lovastatin act on
      melanoma cells, HUVEC or both types of cells. RESULTS: Direct effects of co
      culturing two different malignant melanoma cells (A375 and G361) on the process
      of angiogenesis in vitro was studied with our angiogenesis model, based on human
      dermal fibroblasts and human umbilical vein endothelial cells (HUVEC). Co
      cultures were set up using "sland" and "dispersed seeding" techniques. A
      statistically significant increase in tubule formation in both cases was observed
      compared to controls. The effects of doses equivalent to therapeutic
      concentrations of Lovastatin were analysed. The drug inhibited the growth of all
      cell types, induced apoptosis, and markedly reduced the formation of tubules in
      the angiogenesis model at low concentrations. Its action was successfully
      reversed by the introduction of geranylgeranyl pyrophosphate. CONCLUSION:
      Lovastatin can reduce both tumour (melanoma) cell growth, and the angiogenic
      activity of these cells in co-cultures using an established 2-dimensional model
      angiogenesis system beyond that which would be seen by reduced proliferation
      alone.

PMID- 16573822
TI  - Estrogen-like activity of seafood related to environmental chemical contaminants.
AB  - BACKGROUND: A wide variety of environmental pollutants occur in surface waters,
      including estuarine and marine waters. Many of these contaminants are recognised
      as endocrine disrupting chemicals (EDCs) which can adversely affect the male and
      female reproductive system by binding the estrogen receptor and exhibiting
      hormone-like activities. In this study the estrogenic activity of extracts of
      edible marine organisms for human consumption from the Mediterranean Sea was
      assayed. METHODS: Marine organisms were collected in two different areas of the
      Mediterranean Sea. The estrogenic activity of tissues was assessed using an in
      vitro yeast reporter gene assay (S. cerevisiae RMY 326 ER-ERE). Concentrations of
      polychlorinated biphenyls (PCBs) (congeners 28, 52, 101, 118, 138, 153, 180) in
      fish tissue was also evaluated. RESULTS: Thirty-eight percent of extracts showed
      a hormone-like activity higher than 10% of the activity elicited by 10 nM 17b
      estradiol (E2) used as control. Total PCB concentrations ranged from 0.002 up to
      1.785 ng/g wet weight. Chemical analyses detected different levels of
      contamination among the species collected in the two areas, with the ones
      collected in the Adriatic Sea showing concentrations significantly higher than
      those collected in the Tyrrhenian Sea (p < 0.01). CONCLUSION: The more frequent
      combination of chemicals in the samples that showed higher estrogenic activity
      was PCB 28, PCB 101, PCB 153, PCB 180. The content of PCBs and estrogenic
      activity did not reveal any significant correlation.

PMID- 16573824
TI  - Mouse taste cells with G protein-coupled taste receptors lack voltage-gated
      calcium channels and SNAP-25.
AB  - BACKGROUND: Taste receptor cells are responsible for transducing chemical stimuli
      from the environment and relaying information to the nervous system. Bitter,
      sweet and umami stimuli utilize G-protein coupled receptors which activate the
      phospholipase C (PLC) signaling pathway in Type II taste cells. However, it is
      not known how these cells communicate with the nervous system. Previous studies
      have shown that the subset of taste cells that expresses the T2R bitter receptors
      lack voltage-gated Ca2+ channels, which are normally required for synaptic
      transmission at conventional synapses. Here we use two lines of transgenic mice
      expressing green fluorescent protein (GFP) from two taste-specific promoters to
      examine Ca2+ signaling in subsets of Type II cells: T1R3-GFP mice were used to
      identify sweet- and umami-sensitive taste cells, while TRPM5-GFP mice were used
      to identify all cells that utilize the PLC signaling pathway for transduction.
      Voltage-gated Ca2+ currents were assessed with Ca2+ imaging and whole cell
      recording, while immunocytochemistry was used to detect expression of SNAP-25, a
      presynaptic SNARE protein that is associated with conventional synapses in taste
      cells. RESULTS: Depolarization with high K+ resulted in an increase in
      intracellular Ca2+ in a small subset of non-GFP labeled cells of both transgenic
      mouse lines. In contrast, no depolarization-evoked Ca2+ responses were observed
      in GFP-expressing taste cells of either genotype, but GFP-labeled cells responded
      to the PLC activator m-3M3FBS, suggesting that these cells were viable. Whole
      cell recording indicated that the GFP-labeled cells of both genotypes had small
      voltage-dependent Na+ and K+ currents, but no evidence of Ca2+ currents. A subset
      of non-GFP labeled taste cells exhibited large voltage-dependent Na+ and K+
      currents and a high threshold voltage-gated Ca2+ current. Immunocytochemistry
      indicated that SNAP-25 was expressed in a separate population of taste cells from
      those expressing T1R3 or TRPM5. These data indicate that G protein-coupled taste
      receptors and conventional synaptic signaling mechanisms are expressed in
      separate populations of taste cells. CONCLUSION: The taste receptor cells
      responsible for the transduction of bitter, sweet, and umami stimuli are unlikely
      to communicate with nerve fibers by using conventional chemical synapses.

PMID- 16573825
TI  - The effect of Tai Chi Chuan in reducing falls among elderly people: design of a
      randomized clinical trial in the Netherlands [ISRCTN98840266].
AB  - BACKGROUND: Falls are a significant public health problem. Thirty to fifty
      percent of the elderly of 65 years and older fall each year. Falls are the most
      common type of accident in this age group and can result in fractures and
      subsequent disabilities, increased fear of falling, social isolation, decreased
      mobility, and even an increased mortality. Several forms of exercise have been
      associated with a reduced risk of falling and with a wide range of physiological
      as well as psychosocial health benefits. Tai Chi Chuan seems to be the most
      promising form of exercise in the elderly, but the evidence is still
      controversial. In this article the design of a randomized clinical trial is
      presented. The trial evaluates the effect of Tai Chi Chuan on fall prevention and
      physical and psychological function in older adults. METHODS/DESIGN: 270 people
      of seventy years and older living at home will be identified in the files of the
      participating general practitioners. People will be asked to participate when
      meeting the following inclusion criteria: have experienced a fall in the
      preceding year or suffer from two of the following risk factors: disturbed
      balance, mobility problems, dizziness, or the use of benzodiazepines or
      diuretics. People will be randomly allocated to either the Tai Chi Chuan group
      (13 weeks, twice a week) or the no treatment control group. The primary outcome
      measure is the number of new falls, measured with a diary. The secondary outcome
      measures are balance, fear of falling, blood pressure, heart rate, lung function
      parameters, physical activity, functional status, quality of life, mental health,
      use of walking devices, medication, use of health care services, adjustments to
      the house, severity of fall incidents and subsequent injuries. Process parameters
      will be measured to evaluate the Tai Chi Chuan intervention. A cost-effectiveness
      analysis will be carried out alongside the evaluation of the clinical results.
      Follow-up measurements will be collected at 3, 6 and 12 months after
      randomization. DISCUSSION: As far as we know this is the first trial in Europe
      considering Tai Chi Chuan and fall prevention. This project will answer a
      pragmatic research question regarding the efficacy of Tai Chi Chuan regarding
      fall reduction.

PMID- 16573827
TI  - Combined endoscopic and laparoscopic approach for palliative resection of
      metastatic melanoma of the stomach.
AB  - BACKGROUND: Metastatic tumours of the stomach present a clinical dilemma for the
      surgeon. Palliative surgical resection can alleviate symptoms and prolong
      survival in selected patients. However, previous studies have used open methods
      of surgical resection with potentially high morbidity and mortality. We describe
      the use of laparoscopic wedge resection of the stomach for palliative resection
      of metastatic melanoma to highlight the benefits of this technique. CASE
      PRESENTATION: A 58 year old male was investigated for iron deficiency anaemia
      while under treatment for pulmonary metastatic malignant melanoma. An upper
      gastrointestinal endoscopy revealed a 5 cm diameter ulcer on the anterior wall of
      the stomach, biopsies from the ulcer confirmed metastatic melanoma. Laparoscopic
      wedge resection of the stomach lesion was performed without complication.
      CONCLUSION: Laparoscopic approach has many benefits and is useful for the
      palliative resection of rare tumours of the stomach in order to preserve the
      quality of life. Its use should be considered in selected patients.

PMID- 16573826
TI  - Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases.
AB  - BACKGROUND: New tools are required to improve tuberculosis (TB) diagnosis and
      treatment, including enhanced ability to compare new treatment strategies. The
      ELISPOT assay uses Mycobacterium tuberculosis-specific antigens to produce a
      precise quantitative readout of the immune response to pathogen. We hypothesized
      that TB patients in The Gambia would have reduced ELISPOT counts after successful
      treatment. METHODS: We recruited Gambian adults with sputum smear and culture
      positive tuberculosis for ELISPOT assay and HIV test, and followed them up one
      year later to repeat testing and document treatment outcome. We used ESAT-6, CFP
      10 and Purified Protein Derivative (PPD) as stimulatory antigens. We confirmed
      the reliability of our assay in 23 volunteers through 2 tests one week apart,
      comparing within and between subject variation. RESULTS: We performed an ELISPOT
      test at diagnosis and 12 months later in 89 patients. At recruitment, 70/85 HIV
      negative patients (82%) were ESAT-6 or CFP-10 (EC) ELISPOT positive, 77 (90%)
      were PPD ELISPOT positive. Eighty-two cases (96%) successfully completed
      treatment: 44 (55%; p < 0.001) were EC ELISPOT negative at 12 months, 17 (21%; p
      = 0.051) were PPD ELISPOT negative. Sixty (73%) cured cases had a CFP-10 ELISPOT
      count decrease, 64 (78%) had an ESAT-6 ELISPOT count decrease, 58 (70%) had a PPD
      ELISPOT count decrease. There was a mean decline of 25, 44 and 47 SFU/2 x 105
      cells for CFP-10, ESAT-6 and PPD respectively (p < 0.001 for all). Three of 4 HIV
      positive patients were cured, all 3 underwent ELISPOT reversion; all 4 not cured
      subjects (3 HIV-negative, 1 HIV positive) were ESAT-6, CFP-10 and PPD ELISPOT
      positive at 12 months. CONCLUSION: Successful tuberculosis treatment is
      accompanied by a significant reduction in the M. tuberculosis-specific antigen
      ELISPOT count. The ELISPOT has potential as a proxy measure of TB treatment
      outcome. Further investigation into the decay kinetics of T-cells with treatment
      is warranted.

PMID- 16573828
TI  - Antennal sensilla of two female anopheline sibling species with differing host
      ranges.
AB  - BACKGROUND: Volatile odors are important sensory inputs that shape the behaviour
      of insects, including agricultural pests and disease vectors. Anopheles gambiae
      s.s. is a highly anthropophilic mosquito and is the major vector for human
      malaria in sub-Sahara Africa, while Anopheles quadriannulatus, largely due to its
      zoophilic behaviour, is considered a non-vector species in the same region.
      Careful studies of olfaction in these sibling species may lead to insights about
      the mechanisms that drive host preference behaviour. In the present study, the
      external anatomy of the antenna, the principle olfactory organ in the female
      mosquito of both species, was examined as an initial step toward more detailed
      comparisons. METHODS: Scanning electron and light microscopy were used to examine
      the antennae ultrastructures of adult female An. gambiae s.s. and An.
      quadriannulatus. Sensory structures, called sensilla, were categorized and
      counted; their distributions are reported here as well as densities calculated
      for each species. RESULTS: Both An. gambiae s.s. and An. quadriannulatus bear
      five classes of sensilla on their antennae: chaetica (bristles), trichodea
      (hairs), basiconica (pegs), coeloconica (pitted pegs), and ampullacea (pegs in
      tubes). Female An. quadriannulatus antennae have approximately one-third more
      sensilla, and a proportionally larger surface area, than female An. gambiae s.s.
      antennae. CONCLUSION: The same types of sensilla are found on the antennae of
      both species. While An. quadriannulatus has greater numbers of each sensilla
      type, sensilla densities are very similar for each species, suggesting that other
      factors may be more important to such olfactory-driven behaviours as host
      preference.

PMID- 16573829
TI  - High-grade symptomatic and asymptomatic carotid stenosis in the very elderly. A
      challenge for proponents of carotid angioplasty and stenting.
AB  - BACKGROUND: Carotid angioplasty and stenting (CAS) is often considered as the
      preferred treatment for severe carotid occlusive disease in patients labelled as
      "high risk", including those aged 80 or more. We analyzed 30-day stroke risk and
      death rates after carotid endarterectomy (CEA) for severe symptomatic or
      asymptomatic carotid disease in patients aged 80 or more, by comparison with the
      outcome of CAS reported in the recently- published literature. METHODS: A
      retrospective review was conducted on a prospectively compiled computerized
      database of all primary CEAs performed by a single surgeon at our institution
      from 1990 to 2003. Descriptive demographic data, risk factors, surgical details,
      perioperative strokes and deaths, and other complications were recorded. RESULTS:
      In all, 1260 CEAs were performed in 1099 patients; 1145 were performed in 987
      patients less than 80 years old, and 115 were performed in 112 patients aged 80
      or more. There were 11 perioperative strokes in the 1145 procedures in the
      younger group, for a stroke rate of 0.8%, and no strokes in the 115 procedures in
      the older group. The death rates were 0% for the octogenarians and 0.3% for the
      younger group. CONCLUSION: The conviction that older age means higher risk needs
      to be revised. Patients aged 80 or more can undergo CEA with no more
      perioperative risks than younger patients. Proponents of CAS should bear this in
      mind before recommending CAS as the best therapeutic option for such patients.

PMID- 16573832
TI  - Identifying temporal variation in reported births, deaths and movements of cattle
      in Britain.
AB  - BACKGROUND: The accuracy of predicting disease occurrence using epidemic models
      relies on an understanding of the system or population under investigation. At
      the time of the Foot and Mouth disease (FMD) outbreak of 2001, there were limited
      reports in the literature as to the cattle population structure in Britain. In
      this paper we examine the temporal patterns of cattle births, deaths, imports and
      movements occurring within Britain, reported to the Department for the
      Environment, Food and Rural Affairs (DEFRA) through the British Cattle Movement
      service (BCMS) during the period 1st January 2002 to 28th February 2005. RESULTS:
      In Britain, the number of reported cattle births exhibit strong seasonality
      characterised by a large spring peak followed by a smaller autumn peak. Other
      event types also exhibit strong seasonal trends; both the reported number of
      cattle slaughtered and "on-farm" cattle deaths increase during the final part of
      the year. After allowing for seasonal components by smoothing the data, we
      illustrate that there is very little remaining non-seasonal trend in the number
      of cattle births, "on-farm" deaths, slaughterhouse deaths, on- and off-movements.
      However after allowing for seasonal fluctuations the number of cattle imports has
      been decreasing since 2002. Reporting of movements, births and deaths was more
      frequent on certain days of the week. For instance, greater numbers of cattle
      were slaughtered on Tuesdays, Wednesdays and Thursdays. Evidence for digit
      preference was found in the reporting of births and "on-farm" deaths with
      particular bias towards over reporting on the 1st, 10th and 20th of each month.
      CONCLUSION: This study provides insight into the population and movement dynamics
      of the British cattle population. Although the population is in constant flux,
      seasonal and long term trends can be identified in the number of reported births,
      deaths and movements of cattle. Incorporating this temporal variation in epidemic
      disease modelling may result in more accurate model predictions and may usefully
      inform future surveillance strategies.

PMID- 16573830
TI  - Increased proinflammatory endothelial response to S100A8/A9 after preactivation
      through advanced glycation end products.
AB  - BACKGROUND: Atherosclerosis is an inflammatory disease in which a perpetuated
      activation of NFkappaB via the RAGE (receptor for advanced glycation end
      products)-MAPK signalling pathway may play an important pathogenetic role. As
      recently S100 proteins have been identified as ligands of RAGE, we sought to
      determine the effects of the proinflammatory heterodimer of S100A8/S100A9 on the
      RAGE-NFkappaB mediated induction of proinflammatory gene expression. METHODS:
      Human umbilical vein endothelial cells (HUVEC) were preincubated for 72 h with
      AGE-albumin or unmodified albumin for control, whereas AGE-albumin induction
      resulted in an upregulation of RAGE. Following this preactivation, cells were
      stimulated for 48 h with heterodimeric human recombinant S100A8/S100A9. RESULTS:
      Heterodimeric S100A8/S100A9 enhanced secretion of IL-6, ICAM-1, VCAM-1 and MCP1
      in AGE-albumin pretreated HUVEC in a dose dependent manner. These effects could
      not be detected after stimulation with the homodimeric proteins S100A8, S100A9,
      S100A1 and S100B. The effects of heterodimeric S100A8/S100A9 were reduced by
      inhibition of the MAP-kinase pathways ERK1/2 and p38 by PD 98059 and SB 203580,
      respectively. CONCLUSION: The heterodimeric S100A8/S100A9 might therefore play a
      hitherto unknown role in triggering atherosclerosis in diabetes and renal
      failure, pathophysiological entities associated with a high AGE burden. Thus,
      blocking heterodimeric S100A8/S100A9 might represent a novel therapeutic modality
      in treating atherosclerosis.

PMID- 16573833
TI  - A superior P-H phosphonite: asymmetric allylic substitutions with fenchol-based
      palladium catalysts.
AB  - The fenchol-based P-H phosphonite BIFOP-H exeeds with 65% ee other monodentate
      ligands in the Pd-catalyzed substitution of 1-phenyl-2-propenyl acetate with
      dimethylmalonate.

PMID- 16573831
TI  - Prototypical antipsychotic drugs protect hippocampal neuronal cultures against
      cell death induced by growth medium deprivation.
AB  - BACKGROUND: Several clinical studies suggested that antipsychotic-based
      medications could ameliorate cognitive functions impaired in certain
      schizophrenic patients. Accordingly, we investigated the effects of various
      dopaminergic receptor antagonists--including atypical antipsychotics that are
      prescribed for the treatment of schizophrenia--in a model of toxicity using
      cultured hippocampal neurons, the hippocampus being a region of particular
      relevance to cognition. RESULTS: Hippocampal cell death induced by deprivation of
      growth medium constituents was strongly blocked by drugs including antipsychotics
      (10(-10)-10(-6) M) that display nM affinities for D2 and/or D4 receptors
      (clozapine, haloperidol, (+/-)-sulpiride, domperidone, clozapine, risperidone,
      chlorpromazine, (+)-butaclamol and L-741,742). These effects were shared by some
      caspases inhibitors and were not accompanied by inhibition of reactive oxygen
      species. In contrast, (-)-raclopride and remoxipride, two drugs that
      preferentially bind D2 over D4 receptors were ineffective, as well as the
      selective D3 receptor antagonist U 99194. Interestingly, (-)-raclopride (10(-6)
      M) was able to block the neuroprotective effect of the atypical antipsychotic
      clozapine (10(-6) M). CONCLUSION: Taken together, these data suggest that D2-like
      receptors, particularly the D4 subtype, mediate the neuroprotective effects of
      antipsychotic drugs possibly through a ROS-independent, caspase-dependent
      mechanism.

PMID- 16573834
TI  - Innate immune functions of microglia isolated from human glioma patients.
AB  - BACKGROUND: Innate immunity is considered the first line of host defense and
      microglia presumably play a critical role in mediating potent innate immune
      responses to traumatic and infectious challenges in the human brain. Fundamental
      impairments of the adaptive immune system in glioma patients have been
      investigated; however, it is unknown whether microglia are capable of innate
      immunity and subsequent adaptive anti-tumor immune responses within the
      immunosuppressive tumor micro-environment of human glioma patients. We therefore
      undertook a novel characterization of the innate immune phenotype and function of
      freshly isolated human glioma-infiltrating microglia (GIM). METHODS: GIM were
      isolated by sequential Percoll purification from patient tumors immediately after
      surgical resection. Flow cytometry, phagocytosis and tumor cytotoxicity assays
      were used to analyze the phenotype and function of these cells. RESULTS: GIM
      expressed significant levels of Toll-like receptors (TLRs), however they do not
      secrete any of the cytokines (IL-1beta, IL-6, TNF-alpha) critical in developing
      effective innate immune responses. Similar to innate macrophage functions, GIM
      can mediate phagocytosis and non-MHC restricted cytotoxicity. However, they were
      statistically less able to mediate tumor cytotoxicity compared to microglia
      isolated from normal brain. In addition, the expression of Fas ligand (FasL) was
      low to absent, indicating that apoptosis of the incoming lymphocyte population
      may not be a predominant mode of immunosuppression by microglia. CONCLUSION: We
      show for the first time that despite the immunosuppressive environment of human
      gliomas, GIM are capable of innate immune responses such as phagocytosis,
      cytotoxicity and TLR expression but yet are not competent in secreting key
      cytokines. Further understanding of these innate immune functions could play a
      critical role in understanding and developing effective immunotherapies to
      malignant human gliomas.

PMID- 16573835
TI  - Identification of contrastive and comparable school neighborhoods for childhood
      obesity and physical activity research.
AB  - The neighborhood social and physical environments are considered significant
      factors contributing to children's inactive lifestyles, poor eating habits, and
      high levels of childhood obesity. Understanding of neighborhood environmental
      profiles is needed to facilitate community-based research and the development and
      implementation of community prevention and intervention programs. We sought to
      identify contrastive and comparable districts for childhood obesity and physical
      activity research studies. We have applied GIS technology to manipulate multiple
      data sources to generate objective and quantitative measures of school
      neighborhood-level characteristics for school-based studies. GIS technology
      integrated data from multiple sources (land use, traffic, crime, and census
      tract) and available social and built environment indicators theorized to be
      associated with childhood obesity and physical activity. We used network analysis
      and geoprocessing tools within a GIS environment to integrate these data and to
      generate objective social and physical environment measures for school districts.
      We applied hierarchical cluster analysis to categorize school district groups
      according to their neighborhood characteristics. We tested the utility of the
      area characterizations by using them to select comparable and contrastive schools
      for two specific studies. RESULTS: We generated school neighborhood-level social
      and built environment indicators for all 412 Chicago public elementary school
      districts. The combination of GIS and cluster analysis allowed us to identify
      eight school neighborhoods that were contrastive and comparable on parameters of
      interest (land use and safety) for a childhood obesity and physical activity
      study. CONCLUSION: The combination of GIS and cluster analysis makes it possible
      to objectively characterize urban neighborhoods and to select comparable and/or
      contrasting neighborhoods for community-based health studies.

PMID- 16573836
TI  - Multifactorial approach and superior treatment efficacy in renal patients with
      the aid of nurse practitioners. Design of The MASTERPLAN Study [ISRCTN73187232].
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) are at a greatly increased
      risk of developing cardiovascular disease. Recently developed guidelines address
      multiple risk factors and life-style interventions. However, in current practice
      few patients reach their targets.A multifactorial approach with the aid of nurse
      practitioners was effective in achieving treatment goals and reducing vascular
      events in patients with diabetes mellitus and in patients with heart failure. We
      propose that this also holds for the CKD population. DESIGN: MASTERPLAN is a
      multicenter randomized controlled clinical trial designed to evaluate whether a
      multifactorial approach with the aid of nurse-practicioners reduces
      cardiovascular risk in patients with CKD. Approximately 800 patients with a
      creatinine clearance (estimated by Cockcroft-Gault) between 20 to 70 ml/min, will
      be included. To all patients the same set of guidelines will be applied and
      specific cardioprotective medication will be prescribed. In the intervention
      group the nurse practitioner will provide lifestyle advice and actively address
      treatment goals. Follow-up will be five years. Primary endpoint is the composite
      of myocardial infarction, stroke and cardiovascular mortality. Secondary
      endpoints are cardiovascular morbidity, overall mortality, decline of renal
      function, change in markers of vascular damage and change in quality of life.
      Enrollment has started in April 2004 and the study is on track with 700 patients
      included on October 15th, 2005. This article describes the design of the
      MASTERPLAN study.

PMID- 16573837
TI  - Early detection of left ventricular diastolic dysfunction in Chagas' disease.
AB  - BACKGROUND: Chagas' disease may cause left ventricular diastolic dysfunction and
      its early detection in asymptomatic patients would allow to stratify the risk and
      to optimize medical treatment. The aim of this study is to investigate if
      transmitral Doppler flow can detect early abnormalities of the diastolic left
      ventricular function in patients during the indeterminate phase of Chagas'
      disease, in which the electrocardiogram (ECG), chest x-ray and 2-D echocardiogram
      (2D-echo) are normal. METHODS: a group of 54 patients with Chagas' disease was
      studied and compared to a control group of 27 subjects of similar age. All were
      assessed with an ECG, chest X-ray, 2-D echo, and transmitral Doppler flow.
      RESULTS: both groups had similar values in the 2D-echo. In patients with Chagas'
      disease, the transmitral Doppler showed a higher peak A velocity (control group:
      0.44 m/sec, Chagas group: 0.55 m/sec, p = 0.001), a lower E/A ratio (control
      group: 1.45, Chagas group: 1.22, p < 0.05), and a lengthening of the deceleration
      time of early diastolic filling (control: 138.7 +/- 26.8 msec, Chagas group:
      167.9 +/- 34.6 msec, p = 001), thus revealing an early disorder of the diastolic
      left ventricular function in patients with Chagas' disease. CONCLUSION: in
      patients with Chagas' disease who are in the indeterminate phase, transmitral
      Doppler flow allowed to identify early abnormalities of the left ventricular
      diastolic function, which provide useful clinical information for prognostic
      stratification and treatment.

PMID- 16573838
TI  - LMP-420, a small-molecule inhibitor of TNF-alpha, reduces replication of HIV-1
      and Mycobacterium tuberculosis in human cells.
AB  - BACKGROUND: Co-infections of human immunodeficiency virus (HIV) and Mycobacterium
      tuberculosis (M. Tb) are steadily increasing and represent a major health crisis
      in many developing countries. Both pathogens individually stimulate tumor
      necrosis factor-alpha (TNF) release from infected cells and TNF, in turn,
      enhances the replication of each. A recent report on a Phase I clinical trial
      suggested that etanercept (soluble TNF receptor) might be beneficial in treating
      HIV/M. Tb co-infected patients. We sought to determine if a small molecule
      inhibitor of TNF synthesis and activity could block replication of either
      organism and thus be a potential adjunct to existing drugs targeting these
      agents. RESULTS: LMP-420, a novel anti-inflammatory agent that inhibits TNF, was
      tested for HIV-1 inhibition both alone and in combination with AZT (3' -azido-3
      deoxythymidine). LMP-420 alone was tested against M. Tb. HIV-1 infected human
      peripheral blood mononuclear cells (PBMC) or M. Tb-infected human alveolar
      macrophages (AM) were treated with a single dose of LMP-420 and viral or
      bacterial replication determined after 7 or 5 days respectively. Viral
      replication was determined from supernatant p24 levels measured by ELISA. M. Tb
      replication was determined by bacterial culture of macrophage lysates. LMP-420
      alone inhibited HIV replication over 7 days with an IC50 of approximately 300 nM.
      Combination of LMP-420 with AZT doubled the level of HIV inhibition observed with
      AZT alone. LMP-420 alone inhibited the replication of virulent M. Tb by >80%,
      more than that observed with anti-TNF antibody alone. CONCLUSION: Inhibition of
      TNF with inexpensive, small-molecule, orally-active drugs may represent a useful
      strategy for enhancing the activity of currently-available antiviral and anti-M.
      Tb agents, particularly in those areas where co-infections with these pathogens
      act to synergistically enhance each other.

PMID- 16573839
TI  - Transdermal opioids for cancer pain.
AB  - Patients with moderate to severe malignancy-related pain frequently require the
      use of opioid pharmacotherapy. Unfortunately, many cancer patients continue to be
      prescribed subtherapeutic doses of pain medications resulting in undo suffering
      and diminished quality of life. The choice of analgesic pharmacotherapy should be
      individualized and based on the intensity and etiology of pain reported by the
      patient. Health care providers must be able to readily quantify the relative
      analgesic potency when converting from one opioid to another or from one route of
      administration to another. Transdermal fentanyl is effective and well tolerated
      pharmacotherapy for the cancer pain patients. However, clinicians need to be
      cognizant that the U.S./U.K. manufacturer's recommendations for equilalagesic
      dosing of transdermal fentanyl may result in initial doses that produce
      subtherapeutic levels and unrelieved pain in some patients. A more aggressive
      dosing algorithm for transdermal fentanyl using a 2:1 (mg/day of oral morphine:
      mcg/hr of transdermal fentanyl) conversion ratio that considers both a review of
      the literature and clinical experience should help clinicians individualize
      cancer pain pharmacotherapy. Transdermal buprenorphine is now being prescribed in
      Europe and Australia for chronic and cancer pain management. Buprenorphine's
      mixed agonist/antagonist activity, dosage ceiling, and high affinity to the
      opiate receptor limits its use to those patients who do not already require large
      daily doses of opioids. Thus, buprenorphine may not be an appropriate medication
      for some patients with advanced unremitting cancer pain.

PMID- 16573840
TI  - Primary irritant and delayed-contact hypersensitivity reactions to the freshwater
      cyanobacterium Cylindrospermopsis raciborskii and its associated toxin
      cylindrospermopsin.
AB  - BACKGROUND: Freshwater cyanobacteria are common inhabitants of recreational
      waterbodies throughout the world; some cyanobacteria can dominate the
      phytoplankton and form blooms, many of which are toxic. Numerous reports in the
      literature describe pruritic skin rashes after recreational or occupational
      exposure to cyanobacteria, but there has been little research conducted on the
      cutaneous effects of cyanobacteria. Using the mouse ear swelling test (MEST), we
      sought to determine whether three toxin-producing cyanobacteria isolates and the
      purified cyanotoxin cylindrospermopsin produced delayed-contact hypersensitivity
      reactions. METHODS: Between 8 and 10 female Balb/c mice in each experiment had
      test material applied to depilated abdominal skin during the induction phase and
      10 or 11 control mice had vehicle only applied to abdominal skin. For challenge
      (day 10) and rechallenge (day 17), test material was applied to a randomly
      allocated test ear; vehicle was applied to the other ear as a control. Ear
      thickness in anaesthetised mice was measured with a micrometer gauge at 24 and 48
      hours after challenge and rechallenge. Ear swelling greater than 20% in one or
      more test mice is considered a positive response. Histopathology examination of
      ear tissues was conducted by independent examiners. RESULTS: Purified
      cylindrospermopsin (2 of 9 test mice vs. 0 of 5 control mice; p = 0.51) and the
      cylindrospermopsin-producing cyanobacterium C. raciborskii (8 of 10 test mice vs.
      0 of 10 control mice; p = 0.001) were both shown to produce hypersensitivity
      reactions. Irritant reactions were seen on abdominal skin at induction. Two other
      toxic cyanobacteria (Microcystis aeruginosa and Anabaena circinalis) did not
      generate any responses using this model. Histopathology examinations to determine
      positive and negative reactions in ear tissues showed excellent agreement beyond
      chance between both examiners (kappa = 0.83). CONCLUSION: The irritant properties
      and cutaneous sensitising potential of cylindrospermopsin indicate that these
      toxicological endpoints should be considered by public health advisors and
      reservoir managers when setting guidelines for recreational exposure to
      cyanobacteria.

PMID- 16573841
TI  - Progressive neurological disease induced by tacrolimus in a renal transplant
      recipient: case presentation.
AB  - BACKGROUND: Tacrolimus and cyclosporine, both calcineurin inhibitors, can cause
      neurological side effects. While mild symptoms such as tremor are well
      recognised, severe complications including seizures and encephalopathy are poorly
      documented following renal transplantation. CASE PRESENTATION: We report a 42
      year old man who received a cadaver renal transplant. He received tacrolimus and
      prednisolone. The course was uneventful for 6 weeks when he became intermittently
      confused, with unsteady gait and slurred speech. Following a grand mal convulsion
      he was admitted. He had no focal neurological signs, cerebrospinal fluid was
      normal; electroencephalogram was consistent with temporal lobe partial epilepsy.
      The magnetic resonance imaging of brain showed widespread changes with multiple
      areas of low signal intensity in brain stem and cerebral hemispheres. He was
      readmitted 3 weeks later after further fits, despite anti-convulsant therapy. He
      was psychotic with visual hallucinations, and rapidly became obtunded. Although
      his tacrolimus blood concentration had been kept in the normal range, his
      symptoms improved dramatically when the tacrolimus was stopped. CONCLUSION:
      Severe central nervous system toxicity from calcineurin inhibitors has been
      rarely reported in renal transplantation and we found only one report of
      tacrolimus-induced toxicity in an adult. We believe the condition is frequently
      undiagnosed. It is a very important diagnosis not to miss as the remedy is simple
      and failure may result in unnecessary brain biopsy, as well as irreversible
      injury.

PMID- 16573842
TI  - Decreased CD90 expression in human mesenchymal stem cells by applying mechanical
      stimulation.
AB  - BACKGROUND: Mesenchymal stem cells (MSC) are multipotent cells which can
      differentiate along osteogenic, chondrogenic, and adipogenic lineages. The
      present study was designed to investigate the influence of mechanical force as a
      specific physiological stress on the differentiation of (MSC) to osteoblast-like
      cells. METHODS: Human MSC were cultured in osteoinductive medium with or without
      cyclic uniaxial mechanical stimulation (2000 mustrain, 200 cycles per day, 1 Hz).
      Cultured cells were analysed for expression of collagen type I, osteocalcin,
      osteonectin, and CD90. To evaluate the biomineral formation the content of bound
      calcium in the cultures was determined. RESULTS: After 14 days in culture
      immunfluorescence staining revealed enhancement of collagen type I and
      osteonectin expression in response to mechanical stimulation. In contrast,
      mechanically stimulated cultures stained negative for CD90. In stimulated and
      unstimulated cultures an increase in the calcium content over time was observed.
      After 21 days in culture the calcium content in mechanical stimulated cultures
      was significantly higher compared to unstimulated control cultures. CONCLUSION:
      These results demonstrate the influence of mechanical force on the
      differentiation of human MSC into osteoblast-like cells in vitro. While
      significant enhancement of the biomineral formation by mechanical stimulation is
      not detected before 21 days, effects on the extracellular matrix became already
      obvious after 14 days. The decrease of CD90 expression in mechanically stimulated
      cultures compared to unstimulated control cultures suggests that CD90 is only
      transiently expressed expression during the differentiation of MSC to osteoblast
      like cells in culture.

PMID- 16573843
TI  - Low autochtonous urban malaria in Antananarivo (Madagascar).
AB  - BACKGROUND: The study of urban malaria is an area undergoing rapid expansion,
      after many years of neglect. The problem of over-diagnosis of malaria, especially
      in low transmission settings including urban areas, is also receiving deserved
      attention. The primary objective of the present study was to assess the frequency
      of malaria among febrile outpatients seen in private and public primary care
      facilities of Antananarivo. The second aim was to determine, among the diagnosed
      malaria cases, the contribution of autochthonous urban malaria. METHODS: Two
      cross-sectional surveys in 43 health centres in Antananarivo in February 2003
      (rainy season) and in July 2003 (dry season) were conducted. Consenting
      clinically suspected malaria patients with fever or history of fever in the past
      48 hours were included. Malaria rapid diagnostic tests and microscopy were used
      to diagnose malaria. Basic information was collected from patients to try to
      identify the origin of the infection: autochthonous or introduced. RESULTS: In
      February, among 771 patients, 15 (1.9%) positive cases were detected. Three
      malaria parasites were implicated: Plasmodium. falciparum (n = 12), Plasmodium
      vivax (n = 2) and Plasmodium. ovale (n = 1). Only two cases, both P. falciparum,
      were likely to have been autochthonous (0.26%). In July, among 739 blood smears
      examined, 11 (1.5%) were positive: P. falciparum (n = 9) and P. vivax (n = 2).
      Three cases of P. falciparum malaria were considered to be of local origin
      (0.4%). CONCLUSION: This study demonstrates that malaria cases among febrile
      episodes are low in Antananarivo and autochthonous malaria cases exist but are
      rare.

PMID- 16573844
TI  - Bivariate line-fitting methods for allometry.
AB  - Fitting a line to a bivariate dataset can be a deceptively complex problem, and
      there has been much debate on this issue in the literature. In this review, we
      describe for the practitioner the essential features of line-fitting methods for
      estimating the relationship between two variables: what methods are commonly
      used, which method should be used when, and how to make inferences from these
      lines to answer common research questions. A particularly important point for
      line-fitting in allometry is that usually, two sources of error are present
      (which we call measurement and equation error), and these have quite different
      implications for choice of line-fitting method. As a consequence, the approach in
      this review and the methods presented have subtle but important differences from
      previous reviews in the biology literature. Linear regression, major axis and
      standardised major axis are alternative methods that can be appropriate when
      there is no measurement error. When there is measurement error, this often needs
      to be estimated and used to adjust the variance terms in formulae for line
      fitting. We also review line-fitting methods for phylogenetic analyses. Methods
      of inference are described for the line-fitting techniques discussed in this
      paper. The types of inference considered here are testing if the slope or
      elevation equals a given value, constructing confidence intervals for the slope
      or elevation, comparing several slopes or elevations, and testing for shift along
      the axis amongst several groups. In some cases several methods have been proposed
      in the literature. These are discussed and compared. In other cases there is
      little or no previous guidance available in the literature. Simulations were
      conducted to check whether the methods of inference proposed have the intended
      coverage probability or Type I error. We identified the methods of inference that
      perform well and recommend the techniques that should be adopted in future work.

PMID- 16573845
TI  - An examination of cetacean brain structure with a novel hypothesis correlating
      thermogenesis to the evolution of a big brain.
AB  - This review examines aspects of cetacean brain structure related to behaviour and
      evolution. Major considerations include cetacean brain-body allometry, structure
      of the cerebral cortex, the hippocampal formation, specialisations of the
      cetacean brain related to vocalisations and sleep phenomenology, paleoneurology,
      and brain-body allometry during cetacean evolution. These data are assimilated to
      demonstrate that there is no neural basis for the often-asserted high
      intellectual abilities of cetaceans. Despite this, the cetaceans do have
      volumetrically large brains. A novel hypothesis regarding the evolution of large
      brain size in cetaceans is put forward. It is shown that a combination of an
      unusually high number of glial cells and unihemispheric sleep phenomenology make
      the cetacean brain an efficient thermogenetic organ, which is needed to
      counteract heat loss to the water. It is demonstrated that water temperature is
      the major selection pressure driving an altered scaling of brain and body size
      and an increased actual brain size in cetaceans. A point in the evolutionary
      history of cetaceans is identified as the moment in which water temperature
      became a significant selection pressure in cetacean brain evolution. This
      occurred at the Archaeoceti - modern cetacean faunal transition. The size,
      structure and scaling of the cetacean brain continues to be shaped by water
      temperature in extant cetaceans. The alterations in cetacean brain structure,
      function and scaling, combined with the imperative of producing offspring that
      can withstand the rate of heat loss experienced in water, within the genetic
      confines of eutherian mammal reproductive constraints, provides an explanation
      for the evolution of the large size of the cetacean brain. These observations
      provide an alternative to the widely held belief of a correlation between brain
      size and intelligence in cetaceans.

PMID- 16573846
TI  - Gender and age affect NK1 receptors in the human brain - a positron emission
      tomography study with [18F]SPA-RQ.
AB  - Substance P (SP) is a neurotransmitter and neuromodulator that mediates its
      effects in the brain predominantly via the neurokinin-1 receptors (NK1Rs). NK1Rs
      and SP have been shown clinically to be involved in nausea and emesis after
      chemotherapy (CINV) and have been implicated preclinically in a range of
      neuropsychiatric disorders but unlike CINV their blockade in these conditions
      does not have proven clinical value. We investigated whether age and gender
      affects NK1R binding potential (NK1R-BP; an index of receptor availability) in
      the living human brain using PET and [18F]SPA-RQ, a highly specific NK1R
      antagonist. Forty-five healthy volunteers (35 male and 10 female), aged between
      19 and 55 years were studied. NK1R-BP was estimated using the simplified
      reference tissue model with cerebellum as a reference region. A regression
      analysis indicated that that a loss of NK1R is associated with normal ageing as
      shown by decreased NK1R-BP (average rate 7% per decade). Statistically
      significant negative associations between age and NK1R-BP were observed in
      temporal, parietal and frontal cortex, hippocampus and parahippocampal formation.
      In addition preliminary data were obtained suggesting possible gender differences
      in NK1R-BP in the cortex and putamen with females having a lower NK1R-BP. The
      exact physiological significance of these results remains to be elucidated but
      conceptually they could be involved in age-related CNS disorders or those with
      gender differences in prevalence.

PMID- 16573847
TI  - Fluvoxamine treatment of generalized social anxiety disorder in Japan: a
      randomized double-blind, placebo-controlled study.
AB  - The efficacy of selective serotonin reuptake inhibitors (SSRIs) for the treatment
      of social anxiety disorder (SAD) has been reported in the USA and Europe.
      However, no clinical investigation has been done with SSRIs in Japanese patients
      with SAD. This study was performed to determine the effectiveness and safety of
      fluvoxamine for generalized SAD (GSAD) in Japanese patients. In this double-blind
      study, patients meeting DSM-IV criteria for GSAD were randomized to receive
      treatment with fluvoxamine or placebo for 10 wk. Fluvoxamine treatment was
      initiated at 50 mg/d, and increased by 50 mg weekly to a maximum of 150 or 300
      mg/d. The primary efficacy outcome was mean change from baseline on the Liebowitz
      Social Anxiety Scale - Japanese Version (LSAS-J) total score. The secondary
      outcomes were response according to the Clinical Global Impressions - Global
      Improvement (CGI-I) score and three domains of the Sheehan Disability Scale (SDS;
      used to assess psychosocial impairment). A total of 176 fluvoxamine-treated
      patients and 89 placebo-treated patients were eligible for the efficacy analysis.
      At week 10, the fluvoxamine-treated patients had a significantly greater
      reduction in the LSAS-J total score compared with placebo-treated patients
      (p=0.0197), with significantly more fluvoxamine recipients being at least much
      improved on the CGI-I scale compared with placebo-treated patients (p=0.024).
      Fluvoxamine-treated patients also had better responses on the SDS compared with
      placebo-treated patients (p=0.0208). Fluvoxamine was safe and well tolerated.
      These results suggest that fluvoxamine is effective for the treatment of Japanese
      patients with GSAD.

PMID- 16573848
TI  - Suicidal behaviour and the menstrual cycle.
AB  - BACKGROUND: To investigate the available data regarding possible associations
      between phases of the menstrual cycle and suicidal behaviour. METHOD: A
      systematic search of major relevant databases was performed using appropriate
      search terms. RESULTS: Forty-four relevant studies were identified in total, 13
      pertaining to suicide, two pertaining to both attempted and completed suicide, 23
      to suicide attempts, three to suicide attempts in those suffering from the
      premenstrual syndrome (PMS), three to suicidal ideation and two to repetitive
      self-harming behaviours. A variety of methodologies were used in these studies
      and there were notable differences in the conclusions reached. Studies with
      better methodology suggest that a positive relationship exists between aspects of
      the menstrual cycle and non-fatal suicidal behaviour. Such behaviour appears to
      be more common in those phases of the menstrual cycle when oestrogen levels are
      lowest (the late luteal and follicular phases), and in those suffering from PMS.
      CONCLUSIONS: There appears to be an association between the menstrual cycle and
      non-fatal suicidal behaviours. Interaction between oestrogen and the serotonergic
      system may provide a possible mechanism.

PMID- 16573849
TI  - Quantitative and qualitative analyses of clock drawing in frontotemporal dementia
      and Alzheimer's disease.
AB  - The clock drawing test (CDT) is a widely used cognitive screening test. It is
      useful in identifying focal lesions and cognitive deficits in dementia groups.
      Lately, several studies attempted its use to differentiate between dementia
      subtypes. Although many studies have examined the CDT in dementia populations,
      research into the use of clock drawing in frontotemporal dementia (FTD) is
      limited. We examined quantitative (global) and qualitative (specific error type)
      differences on the CDT between FTD (n = 36) and Alzheimer's disease (AD; n = 25)
      patients and controls without dementia (n = 25). Results showed significantly
      lower overall scores in the dementia groups compared to the control group,
      whereas FTD patients scored significantly higher than the AD group. On
      qualitative analysis, the FTD group had fewer stimulus bound responses,
      conceptual deficits, and spatial or planning errors compared to the AD group. In
      conclusion, both global and error analysis of the CDT helped discriminate the FTD
      group from controls and AD patients.

PMID- 16573850
TI  - Amnestic mild cognitive impairment: diagnostic outcomes and clinical prediction
      over a two-year time period.
AB  - Amnestic mild cognitive impairment (MCI) has been defined as a precursor to
      Alzheimer's disease (AD), although it is sometimes difficult to identify which
      persons with MCI will eventually convert to AD. We sought to predict MCI
      conversion to AD over a two-year follow-up period using baseline demographic and
      neuropsychological test data from 49 MCI patients. Using a stepwise discriminant
      function analysis with Dementia Rating Scale (DRS) Initiation/Perseveration and
      Wechsler Memory Scale, third edition (WMS-III) Visual Reproduction Percent
      Retention scores, we correctly classified 85.7% of the sample as either AD
      converters or MCI nonconverters, with 76.9% sensitivity and 88.9% specificity.
      Adding race, the presence of vascular risk factors, or cholinesterase inhibitor
      use to the analysis did not greatly change the classification rates obtained with
      neuropsychological test data. Examining neuropsychological test cutoff scores
      revealed that DRS Initiation/Perseveration scores below 37 and Visual
      Reproduction Percent Retention scores below 26% correctly identified AD
      converters with 76.9% sensitivity and 91.7% specificity. These results
      demonstrate that commonly administered neuropsychological tests identify persons
      with MCI at baseline who are at risk for conversion to AD within 1-2 years. Such
      methods could aid in identifying MCI patients who might benefit from early
      treatment, in providing prognostic information to patients, and identifying
      potential clinical trial participants.

PMID- 16573851
TI  - The influence of visual and nonvisual attributes in visual object identification.
AB  - To elucidate the role of visual and nonvisual attribute knowledge on visual
      object identification, we present data from three patients, each with visual
      object identification impairments as a result of different etiologies. Patients
      were shown novel computer-generated shapes paired with different labels
      referencing known entities. On test trials they were shown the novel shapes alone
      and had to identify them by generating the label with which they were formerly
      paired. In all conditions the same triad of computer-generated shapes were used.
      In one condition, the labels (banjo, guitar, violin) referenced entities that
      were both visually similar and similar in terms of their nonvisual attributes
      within semantics. In separate conditions we used labels (e.g., spike, straw,
      pencil or snorkel, cane, crowbar) that referenced entities that were similar in
      terms of their visual attributes but were dissimilar in terms of their nonvisual
      attributes. The results revealed that nonvisual attribute information profoundly
      influenced visual object identification. Our patients performed significantly
      better when attempting to identify shape triads whose labels referenced objects
      with distinct nonvisual attributes versus shape triads whose labels referenced
      objects with similar nonvisual attributes. We conclude that the nonvisual aspects
      of meaning must be taken into consideration when assessing visual object
      identification impairments.

PMID- 16573852
TI  - Humor processing, mentalizing, and executive function in normal aging.
AB  - Recent investigations have emphasized the importance of the prefrontal cortex for
      humor processing. Although the prefrontal cortex is thought to be affected by
      normal aging, relatively little work has been carried out to investigate the
      effects of aging on humor processing. In the present investigation participants
      in three age groups were assessed on a humor comprehension task. They then
      answered mentalistic and nonmentalistic questions. Executive tasks were also
      administered. The older group selected significantly fewer correct punchlines
      from alternatives than the other groups. They were also poorer at answering
      mentalistic questions, but did not differ significantly for nonmentalistic
      questions. The findings of the present investigation showed altered in humor
      processing in normal aging, and this appeared to be related to mentalizing
      ability.

PMID- 16573853
TI  - Frontal injury: impairments of fundamental processes lead to functional
      consequences.

PMID- 16573854
TI  - The case for the development and use of "ecologically valid" measures of
      executive function in experimental and clinical neuropsychology.
AB  - This article considers the scientific process whereby new and better clinical
      tests of executive function might be developed, and what form they might take. We
      argue that many of the traditional tests of executive function most commonly in
      use (e.g., the Wisconsin Card Sorting Test; Stroop) are adaptations of procedures
      that emerged almost coincidentally from conceptual and experimental frameworks
      far removed from those currently in favour, and that the prolongation of their
      use has been encouraged by a sustained period of concentration on "construct
      driven" experimentation in neuropsychology. This resulted from the special
      theoretical demands made by the field of executive function, but was not a
      necessary consequence, and may not even have been a useful one. Whilst useful,
      these tests may not therefore be optimal for their purpose. We consider as an
      alternative approach a function-led development programme which in principle
      could yield tasks better suited to the concerns of the clinician because of the
      transparency afforded by increased "representativeness" and "generalisability."
      We further argue that the requirement of such a programme to represent the
      interaction between the individual and situational context might also provide
      useful constraints for purely experimental investigations. We provide an example
      of such a programme with reference to the Multiple Errands and Six Element tests.

PMID- 16573855
TI  - Frontal lobe contributions to recognition and recall: linking basic research with
      clinical evaluation and remediation.
AB  - The role of the human frontal lobes in episodic memory is becoming better
      understood, thanks mainly to focal lesion and neuroimaging studies. Here we
      review some recent findings from basic research on the frontal lobes in memory
      encoding, search, and decision-making at retrieval. For each of these processes,
      researchers have uncovered cases in which frontal memory impairments can be
      attenuated by various task manipulations. We suggest ways in which these findings
      may inform clinical evaluation and rehabilitation of memory problems following
      frontal damage.

PMID- 16573856
TI  - Impairments of emotion and real-world complex behavior following childhood- or
      adult-onset damage to ventromedial prefrontal cortex.
AB  - The behavioral syndrome resulting from damage to the ventromedial prefrontal (VM)
      region presents major challenges for clinical assessment and management, stemming
      from the absence of reliable neurologic or psychometric markers, coupled with
      often debilitating impairments of decision-making and behavior regulation. Damage
      to this region disrupts neural circuitry critical for emotion, which in turn may
      contribute to impairments in real-world competencies. Here we present findings
      from patients with focal lesions in the VM region acquired either in childhood or
      adulthood, and show that there is a relationship between emotional dysfunction
      and impairments in real-world behavioral competencies. Emotion was rated by
      participants' relatives on dimensions including frustration tolerance, lability,
      anxiety, and blunted affect. Real-world competencies were rated by the relatives
      on dimensions including judgment, planning, and initiation, and were evaluated by
      clinician ratings in areas including social, financial, and occupational
      function. VM damage resulted in severe disruption of emotion, and this emotional
      dysfunction accounted for a significant portion of impaired real-world
      competencies. The long-term impairments associated with childhood-onset lesions
      were at least as severe as those resulting from adult-onset damage. Greater focus
      on the contribution of emotional dysfunction to the real-world competencies of
      patients with damage in the VM region may sharpen their neuropsychological
      assessment and facilitate rehabilitation efforts.

PMID- 16573857
TI  - Impairments of procedures for implementing complex language are due to disruption
      of frontal attention processes.
AB  - Production of complex discourse-lengthy, open-ended utterances and narratives
      requires intact basic language operations, but it also requires a series of
      learned procedures for construction of complex, goal-directed communications. The
      progression of clinical disorders from transcortical motor aphasia to dynamic
      aphasia to discourse impairments represents a progression of procedural deficits
      from basic morpho-syntax to complex grammatical structures to narrative and a
      progression of lesions from posterior frontal to polar and/or lateral frontal to
      medial frontal. Two cases of impaired utilization of language exemplify the range
      of impairments from clearly aphasic agrammatic, nonfluency to less and less
      "aphasic" and more and more executive impairments from transcortical motor
      aphasia to dynamic aphasia to narrative discourse disorder. The clinical
      phenomenology of these disorders gradually comes to be more accurately defined in
      the terminology of executive deficits than that of aphasia. The executive
      deficits are, in turn, based on impairments in various components of attention.
      Specific impairments in energizing attention and setting response criteria
      associated, respectively, with lesions in superior medial and left ventrolateral
      frontal regions may cause defective recruitment of the procedures of complex
      language assembly.

PMID- 16573859
TI  - Frontal lobes and attention: processes and networks, fractionation and
      integration.
AB  - The frontal lobes (FL), are they a general adaptive global capacity processor, or
      a series of fractionated processes? Our lesion studies focusing on attention have
      demonstrated impairments in distinct processes due to pathology in different
      frontal regions, implying fractionation of the "supervisory system." However,
      when task demands are manipulated, it becomes evident that the frontal lobes are
      not just a series of independent processes. Increased complexity of task demands
      elicits greater involvement of frontal regions along a fixed network related to a
      general activation process. For some task demands, one or more anatomically
      distinct frontal processes may be recruited. In other conditions, there is a
      bottom-up nonfrontal/frontal network, with impairment noted maximally for the
      lesser task demands in the nonfrontal automatic processing regions, and then as
      task demands change, increased involvement of different frontal (more
      "strategic") regions, until it appears all frontal regions are involved. With
      other measures, the network is top-down, with impairment in the measure first
      noted in the frontal region and then, with changing task demands, involving a
      posterior region. Adaptability is not just a property of FL, it is the fluid
      recruitment of different processes anywhere in the brain as required by the
      current task.

PMID- 16573858
TI  - Is the prefrontal cortex necessary for delay task performance? Evidence from
      lesion and FMRI data.
AB  - Although the prefrontal cortex (PFC) is consistently found to be associated with
      various working memory processes, the necessity of the PFC for such processes
      remains unclear. To elucidate PFC contributions to storage and
      rehearsal/maintenance processes engaged during verbal working memory function, we
      assessed behavior of patients with lesions to the left or right lateral PFC, and
      neural activity of healthy young subjects during fMRI scanning, during
      performance of working memory tasks. We found that PFC lesions did not affect
      storage processes--which is consistent with the notion that posterior cortical
      networks can support simple retention of information. We also found that PFC
      lesions did not affect rehearsal/maintenance processes, which was in contrast to
      our finding that healthy subjects performing a verbal delayed recognition task
      showed bilateral PFC activation. These combined imaging and behavioral data
      suggest that working memory rehearsal/maintenance processes may depend on both
      hemispheres, which may have implications for recovery of function and development
      of rehabilitation therapies after frontal injury.

PMID- 16573860
TI  - Living, non-living and other things. What can be learned nowadays from category
      specific deficits?

PMID- 16573861
TI  - Progressive knowledge loss: a longitudinal case study.
AB  - The evolution of the progressive loss of semantic knowledge of a patient, VZ,
      with lesions mainly affecting the infero-medial temporal lobes, was followed for
      two years. At the beginning of the study VZ's performance was mainly
      characterized by a category-specific deficit for living things and a modality
      specific deficit for perceptual attribute knowledge. As time went on, VZ's
      disorder affected all categories by changing the relationship between category
      and attribute knowledge. Data show that dissociations may change in the course of
      progressive cognitive breakdown, depending on both degeneration stage and task
      demands. VZ's performance is discussed in the light of the most influential
      theoretical accounts. Methodological suggestions regarding longitudinal studies
      of degenerative patients are also put forward.

PMID- 16573862
TI  - A model of neurocognitive function in spina bifida over the life span.
AB  - Spina bifida myelomeningocele (SBM), a neural tube defect that is the product of
      a complex pattern of gene-environment interactions, is associated with naturally
      occurring, systematic variability in the neural phenotype and in environmental
      factors that lead to systematic variability in the cognitive phenotype. We
      characterize the basis for variability in the cognitive phenotype of children
      with SBM with reference to a model of key biological, cognitive, and
      environmental events unfolding over the course of development from infancy to
      middle age. The cognitive phenotype is not domain-specific, but represents
      manifestations of unobservable constructs involving associative and assembled
      processing, the latter directly reflecting the impact of the neural phenotype on
      core deficits involving movement, timing, and attention orienting. The expression
      of the cognitive phenotype is variable, being moderated by features of the neural
      phenotype involving secondary CNS insults (such as hydrocephalus) that impair
      assembled processing, as well as by environmental factors (such as poverty,
      parenting, and education) that impair associative processing. The preservation of
      strengths in associative processing depends in part on the severity of the CNS
      deficits in SBM and the impact of the environment.

PMID- 16573865
TI  - Concerns with complementary and alternative medicines.

PMID- 16573864
TI  - Extrapolation and interpretation.

PMID- 16573866
TI  - Nerve-stimulator-guided repeated pudendal nerve block for treatment of pudendal
      neuralgia.

PMID- 16573867
TI  - Use of the LMA CTrach in unexpected difficult airway: a case report.

PMID- 16573868
TI  - Inexpensive, yet powerful patient data acquisition via Ethernet.

PMID- 16573869
TI  - Rethinking the psychology of tyranny: the BBC prison study.
AB  - This paper presents findings from the British Broadcasting Corporation (BBC)
      prison study - an experimental case study that examined the consequences of
      randomly dividing men into groups of prisoners and guards within a specially
      constructed institution over a period of 8 days. Unlike the prisoners, the guards
      failed to identify with their role. This made the guards reluctant to impose
      their authority and they were eventually overcome by the prisoners. Participants
      then established an egalitarian social system. When this proved unsustainable,
      moves to impose a tyrannical regime met with weakening resistance. Empirical and
      theoretical analysis addresses the conditions under which people identify with
      the groups to which they are assigned and the social, organizational, and
      clinical consequences of either doing so or failing to do so. On the basis of
      these findings, a new framework for understanding tyranny is outlined. This
      suggests that it is powerlessness and the failure of groups that makes tyranny
      psychologically acceptable.

PMID- 16573870
TI  - Tyranny, freedom and social structure: escaping our theoretical prisons.
AB  - Reicher and Haslam's (2006) BBC prison study undermines the idea that people
      passively accept and enact social roles. In this commentary, I point out that
      this idea is an example of Moscovici's (1976) conformity bias and a wider
      stability bias in social psychological theorizing. In many key areas, the science
      prefers analyses that explain how and why social structures, intergroup and power
      relations, personalities and beliefs maintain and reproduce themselves, and
      indeed cannot be changed, rather than how and why society constantly generates
      forces for social change from within itself. This bias distorts reality and
      produces ideas of limited theoretical or practical power. Human psychology does
      not make us prisoners of social structure. It makes us capable of collective
      action to change social structures and in turn re-fashion our identities, roles,
      personalities and beliefs. Society is not a psychological prison but a means of
      expanding human possibilities. A reorientation of theoretical emphasis is
      overdue.

PMID- 16573871
TI  - On rethinking the psychology of tyranny: the BBC prison study.
AB  - This commentary offers a critical evaluation of the scientific legitimacy of
      research generated by television programming interests. It challenges the
      validity of claims advanced by these researchers regarding the Stanford Prison
      Experiment (SPE) and highlights the biases, fallacies and distortions in this
      study conducted for BBC-TV that attempted a partial replication of my earlier
      experiment.

PMID- 16573872
TI  - Debating the psychology of tyranny: fundamental issues of theory, perspective and
      science.
AB  - In our rejoinder, we concentrate on responding to Zimbardo's criticisms. These
      criticisms involve three broad strategies. The first is to turn broad discussion
      about the psychology of tyranny into narrow questions about the replication of
      prison conditions. The second is to confuse our scientific analysis with the
      television programmes of 'The Experiment'. The third is to make unsupported and
      unwarranted attacks on our integrity. All three lines of attack are flawed and
      distract from the important theoretical challenge of understanding when people
      act to reproduce social inequalities and when they act to challenge them. This is
      the challenge that Turner identifies and engages with in his commentary.

PMID- 16573873
TI  - A social representation is not a quiet thing: exploring the critical potential of
      social representations theory.
AB  - Following Moscovici (1972), this paper addresses the questions: What is the aim
      of research within a social representations perspective? Is it to support or to
      criticize the social order? Is it to consolidate or transform it? After a brief
      overview of social representations theory, I argue that while the theory appears
      to have the conceptual tools to begin this critical task, there are serious
      criticisms and points of underdevelopment that need addressing. In order for
      social representations theory to develop into a rigorously critical theory there
      are three controversial issues that require clarification. These are (a) the
      relationship between psychological processes and social practices, (b) the
      reification and legitimization of different knowledge systems, and (c) agency and
      resistance in the co-construction of self-identity. After discussing each issue
      in turn, with illustrations from research on racializing representations, I
      conclude the paper with a discussion of the role of representations in the
      ideological construction and contestation of reality.

PMID- 16573875
TI  - The focus effect and self-positivity in ratings of self-other similarity and
      difference.
AB  - We conducted 2 studies investigating comparative ratings of similarity or
      difference and the thoughts underlying these ratings. Participants compared
      either the self with others (self-->other focus) or others with the self (other-
      >self focus). People expressed higher distinctiveness under self-->other focus
      than under other-->self focus (focus effect) when rating difference in Studies 1
      and 2, and when rating similarity in Study 1. Analyses of verbal reports showed
      that people mentioned the self more than others under self-->other focus, but
      mentioned self and others to the same extent under other-->self focus. Moreover,
      Study 2 showed that participants spontaneously made more positive statements for
      the self under self-->other focus than under other-->self focus. This effect was
      significantly mediated by the number of self-references made. Implications for
      recent models of social judgment are discussed.

PMID- 16573874
TI  - The role of action control in implementing intentions during the first weeks of
      behaviour change.
AB  - Prevailing social cognition models consider behavioural intentions as immediate
      precursors of actions. This view ignores the role of more proximal self
      regulatory processes, such as action control. The latter emerges after an
      intention has been formed and is supposed to maintain the level of intentions
      over time and to translate them into action. Three facets of action control were
      examined in terms of their predictive power for changes in intentions and for
      physical exercise: (a) awareness of standards, (b) self-monitoring, and (c) self
      regulatory effort. A parsimonious 6-item instrument was administered to 122
      cardiac patients at six weekly measurement points in time following
      rehabilitation. A distinction was made between the level of action control and
      the degree of change in action control, applying a latent growth model. While
      awareness of standards remained stable, the other two facets exhibited a linear
      change over the six-week period. Level and change were distinct predictors of
      physical exercise and changes in intentions. These findings emphasize the
      importance of self-regulatory mechanisms in the first weeks of trying to overcome
      a sedentary lifestyle. Action control may be a promising construct to narrow the
      intention-behaviour gap.

PMID- 16573876
TI  - Belief in a just world as moderator of hostile attributional bias.
AB  - To determine the protective effect of 'belief in a just world for self' (BJW-S)
      on hostile attributional bias, 379 adolescents aged 10-16 years, previously
      identified by teacher ratings as high or low troublemakers, were presented with a
      hypothetical frustrating situation where the intent of the frustrating agent
      appeared either benign, hostile, or ambiguous. The analysis indicated that the
      higher the BJW-S, the lower participants reacted aggressively. This effect was
      qualified by 'belief in a just world for others' (BJW-O), indicating that the
      negative relationship between BJW-S and aggressive reaction was weaker as BJW-O
      increased. An interaction between BJW-S, troublemaking level, and the intent
      factor, indicated for high troublemakers in the ambiguous condition that an
      increase in BJW-S decreased aggressive reaction, while this was not the case for
      low troublemakers, thus providing support for the hypothesized buffer effect of
      BJW-S.

PMID- 16573877
TI  - Attributions and personality as predictors of the road rage response.
AB  - This study examined the ability of attributions and personality traits to predict
      the emotional and behavioural components of the road rage response. Participants
      recalled a recent time when they experienced three different anger-provoking
      events when driving. They then rated their behaviours and emotions during the
      event, and their attributions for why the event occurred. Participants also
      completed a battery of personality questionnaires designed to predict their
      responses to the situations. Attributing causality for the anger-arousing event
      to a stable factor in the offending driver was uniquely related to aggressive
      behaviour and anger in all three situations. Hostile and blame attributions
      predicted aggressive behaviour and anger in different situations. In addition to
      dispositional measures of aggressiveness and anger predicting aggressive
      behaviour and anger in each of the anger-provoking situations, other personality
      variables were also related to aspects of the road rage response (e.g.
      conscientiousness, agreeableness, narcissism, and extraversion). Attributions and
      personality traits accounted for unique variance in the outcomes, and there were
      only sporadic effects of attributions partially mediating the relationships
      between personality variables and responses to the anger-provoking situations.
      Therefore, it is unlikely that the relationships between personality traits and
      responses to anger-provoking situations are completely mediated by attributional
      processing.

PMID- 16573878
TI  - Who do we think we are? The effects of social context and social identification
      on in-group stereotyping.
AB  - In this study, in-group stereotyping was examined as a function of variations in
      social context and perceiver factors. The social context consisted of different
      comparison groups and different domains of comparison. Comparison group and
      comparative domain were expected to interact in determining the content of the in
      group stereotype. This prediction was confirmed with in-group stereotyping being
      strongest in conditions where the combination of comparison group and comparative
      domain made the in-group seem most similar to an out-group. The perceiver's level
      of in-group identification was also positively related to the level of in-group
      stereotyping. Moreover, the level of identification was shown to be dependent on
      the immediate social context and mediated the relationship between social context
      and in-group stereotyping. This pattern is explained in terms of a search for in
      group distinctiveness.

PMID- 16573879
TI  - 'His brain is totally different': an analysis of care-staff explanations of
      aggressive challenging behaviour and the impact of gendered discourses.
AB  - Using a discourse analysis on the texts of 10 interviews with care staff, this
      research explored the discourses used by care staff in constructing the
      aggressive challenging behaviours of men and women with learning disabilities.
      The research also explored discourses used differentially to understand the
      aggressive challenging behaviour of one gender. The analysis demonstrated the use
      of two main discourses, an individual pathology discourse which constructed the
      behaviour as originating in factors stable and internal to the client, and a
      context discourse which constructed the behaviour as a response to the client's
      circumstances. Participants used these accounts flexibly within their talk, and
      also used a mixed discourse which constructed the behaviour as due to both
      individual pathology and context. Despite the staff presenting their
      understandings as not being affected by the client's gender, the presence of two
      gendered individualizing discourses within the interviews was also demonstrated.
      Women's behaviour, unlike men's, was constructed with the use of discourses about
      their menstrual cycle or character flaws. The consequences of the use of these
      different discourses are discussed, as are the subject positions which they
      afford for both staff and clients. It is argued that clients are disempowered by
      the individual pathology discourse; that consideration of the broad contexts
      within which care-staff actions are situated may allow them to manage blame
      whilst reflecting on their practice, and that the impact of gender stereotypes on
      the understandings staff have of a client's behaviour should be a legitimate area
      for consideration in clinical practice.

PMID- 16573976
TI  - The state of educational intervention research as viewed through the lens of
      literacy intervention.
AB  - The characteristics of educational intervention research are reviewed:
      Educational intervention research is inspired by diverse theories, targeted at a
      variety of simple to very complex interventions, and includes a variety of
      methods and measurements. Some interventions have been studied much more than
      others, with the more studied ones often summarized in meta-analyses and other
      integrative reviews. The study of some of the more complex interventions pose new
      ethical challenges. Although some intervention research impacts educational
      practice and policy, much more could and probably should.

PMID- 16573977
TI  - Developmental dynamics between mathematical performance, task motivation, and
      teachers' goals during the transition to primary school.
AB  - BACKGROUND: It has been suggested that children's learning motivation and
      interest in a particular subject play an important role in their school
      performance, particularly in mathematics. However, few cross-lagged longitudinal
      studies have been carried out to investigate the prospective relationships
      between academic achievement and task motivation. Moreover, the role that the
      classroom context plays in this development is largely unknown. AIMS: The aim of
      the study was to investigate the developmental dynamics of maths-related
      motivation and mathematical performance during children's transition to primary
      school. The role of teachers' pedagogical goals and classroom characteristics on
      this development was also investigated. SAMPLE: A total of 196 Finnish children
      were examined four times: (0) in October during their preschool year; (1) in
      October and (2) April during their first grade of primary school; and (3) in
      October during their second grade. METHOD: Children's mathematical performance
      was tested at each measurement point. Task motivation was examined at measurement
      points 2, 3, and 4 using the Task-value scale for children. First-grade teachers
      were interviewed in November about their pedagogical goals and classroom
      characteristics. RESULTS AND CONCLUSIONS: The results showed that children's
      mathematical performance and related task motivation formed a cumulative
      developmental cycle: a high level of maths performance at the beginning of the
      first grade increased subsequent task motivation towards mathematics, which
      further predicted a high level of maths performance at the beginning of the
      second grade. The level of maths-related task motivation increased in those
      classrooms where the teachers emphasized motivation or self-concept development
      as their most important pedagogical goal.

PMID- 16573978
TI  - Parental interest in children's education, children's self-esteem and locus of
      control, and later educational attainment: twenty-six year follow-up of the 1970
      British Birth Cohort.
AB  - BACKGROUND: Few studies have investigated if mother's interest and father's
      interest in child's education are linked to educational attainment via their
      impact on child's self-esteem and locus of control. AIMS: (1) To investigate
      (after controlling for known confounding factors) the long-term effect of
      mother's and father's interest in child's education at age 10 and child's locus
      of control and self-esteem at age 10 in educational attainment at age 26; and (2)
      to explore if mother's interest and father's interest in child's education are
      linked to child's educational attainment via their effect in increasing child's
      self-esteem and internal locus of control. SAMPLE: The study used longitudinal
      data from sweeps of the 1970 British Cohort Study (BCS70). The initial sample was
      those 1,737 men and 2,033 women with valid data on age 10 self-esteem, locus of
      control, father's interest, mother's interest, and age 26 educational attainment.
      Of these, 1,326 men and 1,578 women were included in the final analysis. METHOD:
      The birth to age 10 factors that were controlled for were birth weight, parental
      social class, socio-economic disadvantage, emotional/behavioural problems,
      cognitive ability, and mother's educational attainment. RESULTS: At the
      multivariate level, internal locus of control and mother's interest (but not self
      esteem) were significantly related to educational attainment in both men and
      women. Father's interest was a significant predictor of educational attainment
      only in women. Parent's interest was not linked to educational attainment via its
      impact on child's self-esteem or locus of control. Self-esteem predicted
      educational attainment in both genders by increasing internal locus of control,
      and fathers' interest predicted educational attainment in men by increasing
      mother's involvement. CONCLUSION: Although mothers' and fathers' interest in
      their children's education were not linked to educational attainment via their
      impact on children's self-esteem or locus of control, they were significant
      predictors of educational attainment especially in daughters.

PMID- 16573979
TI  - The belief in a negative interdependence of math and verbal abilities as
      determinant of academic self-concepts.
AB  - BACKGROUND: The internal/external frame of reference (I/E) model by Marsh (1986)
      assumes intra-individual dimensional comparisons in which students compare their
      own achievements in one subject with their achievements in other subjects. These
      comparison processes should lead to negative paths from achievement in one
      subject (e.g. maths) on self-concept in another subject (e.g. verbal domains).
      AIMS: Within this study, we investigated the impact of students' belief in a
      negative interdependence of maths and verbal abilities, that is, whether students
      think of maths and verbal abilities as negatively correlated or not, on the
      impact of dimensional comparisons. METHODS: Maths and German grades, academic
      self-concepts in maths and German, and a new scale on the beliefs in a negative
      interdependence of maths and verbal abilities students were assessed (N = 1,443).
      RESULTS: The importance of the negative interdependence beliefs could be shown:
      stronger beliefs in a negative interdependence of maths and verbal ability are
      accompanied by more negative path coefficients from grades in one subject to
      academic self-concepts in the other subject. CONCLUSIONS: Dimensional comparisons
      seem to be of particular importance for students with negative interdependence
      beliefs.

PMID- 16573980
TI  - Peer and teacher bullying/victimization of South Australian secondary school
      students: prevalence and psychosocial profiles.
AB  - This study examined the nature and prevalence of bullying/victimization by peers
      and teachers reported by 1,284 students (mean age = 15.2 years) drawn from a
      representative sample of 25 South Australian government and private schools.
      Students completed a self-report survey containing questions relating to teacher
      and peer-related bullying, measures of psychosocial adjustment, and personality.
      The results showed that students could be clearly differentiated according to the
      type of victimization they had experienced. Students reporting peer victimization
      typically showed high levels of social alienation, poorer psychological
      functioning, and poorer self-esteem and self-image. By contrast, victims of
      teacher victimization were more likely to be rated as less able academically, had
      less intention to complete school and were more likely to be engaged in high-risk
      behaviours such as gambling, drug use and under-age drinking. Most bullying was
      found to occur at school rather than outside school and involved verbal
      aggression rather than physical harm. Boys were significantly more likely to be
      bullied than girls, with the highest rates being observed amongst boys attending
      single-sex government schools. Girls were more likely to be subject to bullying
      if they attended coeducational private schools. The implications of this work for
      enhancing school-retention rates and addressing psychological distress amongst
      adolescent students are discussed.

PMID- 16573981
TI  - Arab and Jewish elementary school students' perceptions of fear and school
      violence: understanding the influence of school context.
AB  - This inquiry explores variables that predict elementary school students' fear of
      attending school due to school violence and their overall judgments of school
      violence as a problem. Using a nationally representative sample (Israel) of 5,472
      elementary-school-aged children, this study tested the hypotheses that: (a) young
      students' personal fear of attending school due to violence, and (b) students'
      assessment of a school violence problem, are best understood as separate
      conceptual constructs. Structural equation modelling was used to test the
      proposed theoretical model for the sample as a whole and separately for across
      gender and for Arab and Jewish students. Student fear of attending school due to
      violence was related directly to experiences of personal victimization on school
      grounds by students and teachers. Children's judgments of their schools' overall
      violence problem were influenced directly by the school climate, risky peer-group
      behaviours, and personal victimization. The findings provide evidence that the
      proposed theoretical model applies across gender groups and for both Arab and
      Jewish students. Implications for policy, theory, and future research are
      highlighted.

PMID- 16573982
TI  - The educational impact of team-skills training: preparing students to work in
      groups.
AB  - BACKGROUND: Despite a vast literature on collaborative learning (CL), there is
      little research on preparing students to work collaboratively. AIMS: This two
      phase evaluation investigated whether team-skills training could enhance the
      performance of collaborative groups through the introduction of a team
      development programme to a group-based undergraduate key-skills unit. SAMPLE:
      Phase 1 compared two consecutive cohorts of second-year students, Cohort 1 (N =
      94) who received no preparation, and Cohort 2 (N = 113) who received team-skills
      training. Phase 2 added Cohort 3 (N = 88), who also received team-skills
      training, to extend the analysis. METHOD: In Phase 1, students in both Cohorts 1
      and 2 worked on a series of curriculum based key-skill tasks across two
      semesters. Students worked in one group in Semester 1 and were then formed into
      new groups for Semester 2. Effects of the training were measured by student group
      marks and key-skill ratings. RESULTS: Marks and key-skill ratings were
      significantly higher for the trained cohort in Semester 1 (p < .01). However, in
      Semester 2 performance reduced for the trained cohort in comparison to Semester
      1. To explore this further, Phase 2 of the study evaluated Cohort 3, where after
      training, collaborative groups remained intact throughout the academic year.
      Results for Cohort 3 showed no attenuation of performance effects in Semester 2.
      CONCLUSIONS: Phase 1 results support the use of team-skills training to enhance
      CL group performance. The findings for Phase 2 suggest that these benefits may be
      lost if training groups are disrupted.

PMID- 16573983
TI  - An exploration of the relationship between academic and experiential learning
      approaches in vocational education.
AB  - BACKGROUND: Research on individual learning approaches (or learning styles) is
      split in two traditions, one of which is biased towards academic learning, and
      the other towards learning from direct experience. AIMS: In the reported study,
      the two traditions are linked by investigating the relationships between school
      based (academic) and work-based (experiential) learning approaches of students in
      vocational education programs. SAMPLES: Participants were 899 students of a Dutch
      school for secondary vocational education; 758 provided data on school-based
      learning, and 407 provided data on work-based learning, resulting in an overlap
      of 266 students from whom data were obtained on learning in both settings.
      METHODS: Learning approaches in school and work settings were measured with
      questionnaires. Using factor analysis and cluster analysis, items and students
      were grouped, both with respect to school- and work-based learning. RESULTS: The
      study identified two academic learning dimensions (constructive learning and
      reproductive learning), and three experiential learning dimensions (analysis,
      initiative, and immersion). Construction and analysis were correlated positively,
      and reproduction and initiative negatively. Cluster analysis resulted in the
      identification of three school-based learning orientations and three work-based
      learning orientations. The relation between the two types of learning
      orientations, expressed in Cramer's V, appeared to be weak. CONCLUSIONS: It is
      concluded that learning approaches are relatively context specific, which implies
      that neither theoretical tradition can claim general applicability.

PMID- 16573984
TI  - Life goals, approaches to study and performance in an undergraduate cohort.
AB  - BACKGROUND: Two main approaches to studying have been distinguished by several
      researchers, the deep approach and the surface approach. In addition, an
      achieving or strategic approach employs either deep or surface strategies,
      depending on the demands of the task. AIMS: The present study investigated
      factors contributing to the choice of preferred study approach at university and
      relations between these factors and academic performance. METHOD: A questionnaire
      was mailed to a complete cohort of entrants in a college of London University in
      the UK. A further questionnaire was sent part way through the second year of the
      course. RESULTS: Consistent relations were found between general life goals and
      approaches to study, with the deep approach being associated with altruistic life
      goals and the surface approach being associated with wealth and status life
      goals. The achieving approach was related to both types of life goal, but more
      strongly to wealth and status life goals. Older students, those with superior
      results in Advanced Level examinations, those reporting more use of the achieving
      approach, and those with less interest in wealth and status life goals, produced
      better academic results. Study approaches became more surface-oriented and less
      deep and achieving-oriented over the first year of study, but these changes were
      unrelated to academic performance. CONCLUSIONS: Approaches to study form part of
      a wider approach to life in general. Students adopting the achieving approach to
      study performed better. Though the achieving approach tended to weaken as the
      course proceeded, this change was unrelated to performance.

PMID- 16573985
TI  - Individual contributory factors in teacher stress: the role of achievement
      striving and occupational commitment.
AB  - Workplace stress and its impact upon retention levels are becoming an increasing
      concern within the teaching profession (Brown, Davis, & Johnson, 2002; Jarvis,
      2002). Research has largely focused upon the effects of environmental factors,
      whilst noting that it is the interplay between the individual and the environment
      which may hold the key to understanding this problem (Cox, 1978; Parkes, 1994).
      Identifying individual contributory factors is essential in understanding why,
      under the same environmental conditions, some people suffer much greater levels
      of stress than others. This study examined the influence of Type A behaviour,
      personal achievement strivings, occupational commitment, gender and
      nature/experience of teaching on perceived workplace stress within the teaching
      profession (N = 95). It was predicted that perceived stress would be strongest
      amongst those reporting higher levels of these factors. A multiple regression
      analysis indicated that there was a positive relationship between Type A
      behaviour, personal achievement strivings, and perceived stress. The relationship
      between perceived stress and occupational commitment, however, was found to be
      negative. The possible explanations for these findings, and potential
      implications, are discussed. Future research plans are outlined for exploring the
      relationships between these individual contributory factors and environmental
      stressors.

PMID- 16574028
TI  - Costs of physical and mental comorbidities among employees: a comparison of those
      with and without bipolar disorder.
AB  - OBJECTIVE: To compare the cost and utilization of health care services for
      various comorbid conditions among employees with bipolar disorder (BPD) and two
      other population cohorts: employees without BPD and employees with other mental
      disorders (OMD). METHODS: Retrospective database analysis on a 2-year study
      period, from January 1, 2001, through December 31, 2002 using adjudicated health
      insurance medical claims on more than 230 000 employees plus their eligible
      dependents. Study comparisons were performed among employees with BPD (cohort
      BPD), employees without BPD (cohort NBD), and employees with OMD (cohort OMD).
      Outcome measures included the cost and utilization of health services for various
      comorbid conditions as defined by the Agency for Healthcare Research and Quality
      (AHRQ); using 261 specific categories (SCs) and the 17 Major Diagnostic
      Categories (MDCs). RESULTS: Employees in cohort BPD (n = 761) had greater average
      annual medical and prescription drug costs than the two other employee cohorts.
      Costs for cohort BPD were significantly greater (p <or= 0.05) than for cohort NBD
      (n = 229 145) for six of the 17 MDCs, including the categories of mental
      disorders (2036 dollars vs. 65 dollars), injury and poisoning (544 dollars vs.
      162 dollars), musculoskeletal/connective tissue (607 dollars vs. 315 dollars),
      other conditions (274 dollars vs. 134 dollars), respiratory system (217 dollars
      vs. 104 dollars), and nervous system/sensory organs (225 dollars vs. 119
      dollars). Similarly, comparisons across AHRQ's 261 SCs found the annual medical
      costs associated with BPD were greater in 137 (52%) of the 261 categories.
      Differences between cohort BPD and cohort OMD (n = 26 776) were significant (p
      <or= 0.05) in three MDCs, with BPD 3.4 times greater than OMD in the mental
      disorders category: 2036 dollars vs. 596 dollars, respectively. CONCLUSION:
      Employees with BPD have greater cost and utilization of services due to various
      mental and physical comorbidities than either employees without BPD or employees
      with OMD. The findings are consistent with current literature concerning the
      comorbidities associated with BPD, and suggest that further longitudinal and
      observational investigation is necessary to attempt to improve diagnosis and
      treatment of not only BPD, but also associated targeted diseases commonly found
      in employees with BPD.

PMID- 16574029
TI  - Comparing outcomes in patients with persistent asthma: a registry of two
      therapeutic alternatives.
AB  - OBJECTIVE: Clinical trials have demonstrated improved efficacy of fluticasone
      propionate/salmeterol (100/50 mcg) in a single device (FSC) compared with
      montelukast (10 mg) (MON). This study was designed to assess asthma control,
      asthma-related quality of life, asthma-related emergency department (ED)
      visit/hospitalization, treatment-related satisfaction, and productivity losses in
      patients newly started on FSC or MON. RESEARCH DESIGN AND METHODS: Patients who
      were newly prescribed FSC or MON during a regularly scheduled office visit were
      enrolled in a prospective observational study by nearly 500 physicians from eight
      managed care plans. Patient survey data were collected at baseline and at months
      1, 3, 6, and 12, to measure study outcomes. ED visits/inpatient stays were
      reported from commercial claims data. Multivariate analyses assessed 12-month
      outcomes, controlling for several baseline patient characteristics. RESULTS: A
      total of 1414 patients >or= 15 years old were enrolled in the registry (FSC, n =
      1061; MON, n = 353), 90% of which completed a 12-month survey. FSC patients had
      significantly greater improvement in both asthma control and quality of life, and
      reported significantly higher satisfaction with their medication (p = 0.003) and
      fewer days at work/school with asthma symptoms (p = 0.04) than MON. Other
      parameters of productivity losses such as missed work/school days due to asthma
      were not significantly different between the two groups. FSC use was also
      significantly associated with a lower risk of an asthma-related ED
      visit/hospitalization compared with MON (odds ratio = 0.35, 95% confidence
      interval: 0.15-0.92). CONCLUSION: In a 12-month office-based observational study,
      patients age 15 and older with persistent asthma, newly started on FSC, improved
      in symptom, quality of life, treatment, and utilization-related outcomes compared
      with patients newly started on MON. These results should be interpreted in light
      of the inherent limitations of non-randomized, uncontrolled studies.

PMID- 16574030
TI  - Resource utilization with fluticasone propionate and salmeterol in a single
      inhaler compared with other controller therapies in children with asthma.
AB  - OBJECTIVE: To determine resource utilization in controller naive children
      diagnosed with asthma receiving initial therapy with fluticasone propionate (FP)
      and salmeterol (SAL) in a single inhaler (FSC), FP alone, montelukast (MON),
      inhaled corticosteroid (ICS) + SAL from separate inhalers, or ICS + MON. RESEARCH
      DESIGN AND METHODS: A retrospective, observational, 18-month (6-month pre-index
      and 12-month follow-up) database study using medical and pharmacy claims from a 5
      million member managed care organization. Multivariate modeling was used to
      evaluate post-index resource utilization and asthma-related costs. Refill rates
      during the 12-month follow-up period were compared across cohorts. RESULTS: The
      study included controller-naive children (n = 9192) aged 4-17 years with an
      asthma diagnosis. Children treated with FSC were significantly less likely to
      receive additional prescriptions for short-acting beta-agonists compared with all
      other cohorts (p <or= 0.007) and oral corticosteroids compared with the MON, ICS
      + SAL, and ICS + MON cohorts (p <or= 0.009). Children receiving FSC were also
      significantly less likely to add another controller therapy compared with
      children started on FP alone, MON, or ICS + SAL (p <or= 0.001) and to receive
      care in an emergency department or hospital compared with children receiving ICS
      + MON (p < 0.001). The number of prescriptions for FSC in the 12-month post-index
      period was greater (p < 0.05) than the number of ICS claims in the FP, ICS + SAL,
      and ICS + MON cohorts. Compared with FSC, the adjusted total asthma-related post
      index costs were greater (p <or= 0.008) in the MON and ICS + MON cohorts.
      Although adherence was greater with MON compared with FSC, MON was associated
      with less favorable clinical outcomes and greater resource utilization and costs.
      CONCLUSION: FSC in children is associated with improved clinical outcomes and
      decreased resource utilization compared with other controller regimens.

PMID- 16574031
TI  - Review of the rebound phenomenon in new anticoagulant treatments.
AB  - BACKGROUND: The launch of new anticoagulant treatments has sparked debate as to
      the optimal drug to use for primary prevention of venous thromboembolism (VTE) in
      major orthopaedic surgery, for the treatment of VTE, and for stroke prevention in
      atrial fibrillation, taking into account both efficacy and tolerability. Newer
      drugs such as fondaparinux and ximelagatran have shown improvements in short-term
      efficacy or convenience, but such effects may be offset by reduced tolerability.
      They also raise the question of a possible delayed increase in thromboembolic
      events after these drugs are stopped, the so-called 'rebound effect'. OBJECTIVE:
      To review pharmacological and clinical data describing the rebound effect
      associated with new and standard anticoagulant drugs. RESEARCH DESIGN AND
      METHODS: Computerized searches, covering the period 1960-2005 for the historical
      background and physiopathology review, and from 1999 to 2005 for the clinical
      trial analysis, were performed on BIOSIS, PubMed and clinicaltrials.gov
      databases. The terms 'rebound', 'anticoagulant', and 'heparin' were used. Only
      articles written in English were reviewed. Articles with drug interactions from
      other therapeutic classes or types of vascular surgery and commentary articles
      were excluded. RESULTS: Available data in relation to a possible rebound
      phenomenon following cessation of active treatment are very limited. Results
      coming mainly from orthopaedic surgery trials suggest an increased rate of venous
      or arterial thromboembolic events with newer anticoagulants, compared with
      standard anticoagulant therapy. An increase in the rate of serious arterial
      adverse events has, for example, been observed in VTE patients treated with
      ximelagatran relative to those receiving warfarin/placebo (short-term exposure:
      0.75% vs 0.26%, p < 0.05; long-term exposure: 1.70% vs 0.70%, p <or= 0.1).
      CONCLUSIONS: Further clinical trials or meta-analyses are needed before we can
      determine whether the unexpected thromboembolic events found with newer
      anticoagulants can be linked to a rebound effect on treatment cessation.

PMID- 16574033
TI  - A retrospective claims database analysis to assess patterns of interstitial
      cystitis diagnosis.
AB  - OBJECTIVE: Interstitial cystitis (IC) is often misdiagnosed as one of several
      other conditions manifesting similar symptoms. This analysis assesses the
      potential extent of IC misdiagnosis while considering concomitant conditions in a
      managed care population and identifies predictors of IC diagnosis. RESEARCH
      DESIGN AND METHODS: Administrative insurance claims data covering 1.7 million
      lives (1999-2003) were analyzed. Insurance enrollees with >or= 1 IC diagnosis
      (ICD-9-CM of 595.1x) were identified as IC patients. A random sample of non-IC
      controls was selected using a 10:1 matching ratio. Six-month incidence rates of
      'commonly misdiagnosed conditions', (overactive bladder, urinary tract infection,
      chronic pelvic pain, endometriosis, prostatitis) were compared before and after
      patients' initial IC diagnosis and the reduction in incidence rate of commonly
      misdiagnosed conditions was used as a suggestive measure of the extent of IC
      misdiagnosis. The Kaplan-Meier method was used to assess the extent that commonly
      misdiagnosed conditions were predictors of subsequent IC. A Cox Proportional
      Hazards regression model (that adjusts for patient demographics, concomitant and
      misdiagnosed conditions) was used to estimate the hazard ratio (HR) of these
      conditions. Similar analyses were performed for the 'commonly concomitant
      conditions' (fibromyalgia, irritable bowel syndrome, vulvodynia). RESULTS: There
      were 992 IC patients and 9920 controls identified. The reduced incidence of
      commonly misdiagnosed conditions after initial IC diagnosis suggests that the
      misdiagnosis rate could be as high as 38% within the 6-month period before
      initial IC diagnosis. CONCLUSIONS: Diagnoses of commonly misdiagnosed conditions
      are significant predictors of future IC diagnosis. When overlooked, potential
      misdiagnosis of IC can lead to underestimation of the true prevalence of IC.
      Similarly, diagnoses of commonly concomitant conditions are significant
      predictors of future IC diagnosis. These initial findings based on claims data
      suggest hypotheses for further investigation with clinical data. These results
      suggest more consideration of IC as a diagnosis is warranted, especially when
      certain diagnoses are repeatedly made and the resulting treatments do not
      alleviate the patient's symptoms.

PMID- 16574032
TI  - Effect of age on response to rivastigmine or donepezil in patients with
      Alzheimer's disease.
AB  - BACKGROUND: Younger Alzheimer's disease (AD) patients appear to differ
      genetically and neuropathologically from older AD patients, and may experience a
      more aggressive disease course compared with older patients. A randomised trial
      investigated the efficacy and tolerability of rivastigmine, an inhibitor of
      acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and donepezil, an
      AChE-selective inhibitor, in patients with AD over a 2-year period. This
      retrospective analysis investigated whether younger and older patients showed
      differential tolerability and efficacy responses to cholinesterase inhibitor
      treatment. METHODS: For the current analysis, patients were divided according to
      age at baseline: those aged < 75 years and those aged >or= 75 years. Efficacy
      measures were the Severe Impairment Battery (SIB), Neuropsychiatric Inventory
      (NPI), Global Deterioration Scale (GDS), Mini-Mental State Examination (MMSE) and
      the AD Cooperative Study Activities of Daily Living scale (ADCS-ADL). Changes in
      efficacy parameters and adverse event frequencies were calculated for
      rivastigmine and donepezil-treated patients in both age groups. Exploratory
      analyses were also conducted on SIB, ADCS-ADL and NPI in patients who consented
      to pharmacogenetic testing at baseline. Genotyping of the apolipoprotein E (APOE)
      epsilon4 allele and the BuChE K-variant was conducted using the TaqMan assay.
      Main efficacy analyses were based on an intent-to-treat last observation carried
      forward (ITT-LOCF) population. RESULTS: Of the 994 patients who received the
      study drug, 362 (36.4%) were younger than 75 years and 632 (63.6%) were aged 75
      years or over. Rivastigmine provided significant benefits in younger patients
      compared with donepezil on the NPI-10, NPI-12, NPI-D, GDS and ADCS-ADL (all p <
      0.05, ITT-LOCF). With the exception of the NPI-D in favour of donepezil (p <
      0.05, ITT-LOCF), no significant treatment differences were observed in older
      patients. Younger patients with two wild-type BuChE alleles had a significantly
      greater response to rivastigmine than donepezil on the ADCS-ADL (p < 0.01, ITT
      LOCF) and SIB (p < 0.05, ITT-LOCF). The most common adverse events were nausea
      and vomiting and these were more frequent in rivastigmine-treated patients.
      CONCLUSION: In this sub group analysis, patients younger than 75 years of age
      showed greater treatment responses to rivastigmine than donepezil. Analysis of
      response by BuChE genotype suggests that this differential effect may be due to
      the inhibition of BuChE, in addition to AChE, by rivastigmine.

PMID- 16574034
TI  - A comparison of the skin irritation potential of transdermal fentanyl versus
      transdermal buprenorphine in middle-aged to elderly healthy volunteers.
AB  - OBJECTIVE: Establishing local tolerability of transdermal opioid systems is
      important as more systems become available for use in a range of indications. We
      compared the skin irritation potential of a single application of transdermal
      fentanyl (Durogesic D-trans; DDTDF) and transdermal buprenorphine (Transtec; TDB)
      patches in healthy volunteers. METHODS: 46 healthy males and females (mean age
      [range]: 59.6 [50-69] years) with healthy skin received a single dose of both the
      DDTDF 25 mug/h patch and the TDB 35 mug/h patch in a randomised order under
      naltrexone cover. The incidence and severity of erythema was assessed at various
      timepoints after patch removal. RESULTS: There was a non-significant trend
      towards a higher incidence of erythema 60 min after patch removal with TDB
      compared with DDTDF. The severity of erythema at 60 min and the incidence of
      erythema at 72 h after patch removal were significantly higher with TDB than with
      DDTDF (p = 0.01 and 22% versus 4.9%, p = 0.04, respectively). In general, the
      results from the chromametric assessment of treated skin were in agreement. The
      incidence of topical adverse events (AEs) was lower with DDTDF than with TDB (one
      versus six events) and subjects preferred the DDTDF patch and felt it was less
      noticeable on the skin. The DDTDF patch was considered less painful to remove,
      and, consistent with that, the TDB patch was judged to have better adhesion.
      Twenty-one subjects reported systemic AEs with DDTDF plus naltrexone and 22 with
      TDB plus naltrexone, most of which were considered treatment-related, 34 and 60
      AEs, respectively. CONCLUSIONS: Local tolerability of transdermal opioid systems
      should be considered when making a therapeutic choice. Even after a single
      application in healthy volunteers, differences in local tolerability, assessed
      both clinically and by chromametry, and patch comfort were shown between DDTDF
      and TDB, in favour of DDTDF.

PMID- 16574035
TI  - Reaching goal in hypercholesterolaemia: dual inhibition of cholesterol synthesis
      and absorption with simvastatin plus ezetimibe.
AB  - Lowering serum cholesterol levels reduces the risk of coronary heart disease
      (CHD)-related events. Statins are commonly prescribed as first-line treatment but
      many patients at high-risk for CHD still fail to reach their cholesterol or low
      density lipoprotein cholesterol (LDL-C) goals with statin monotherapy. National
      and international guidelines for the prevention of CHD recommend the modification
      of lipid profiles and particularly LDL-C [e.g. the National Cholesterol Education
      Program Adult Treatment Panel III (NCEP ATP III; 2001) and Third Joint Task Force
      of European and other Societies on Cardiovascular Disease Prevention in Clinical
      Practice (2003) Guidelines]. Several recent clinical trials indicated an added
      benefit from aggressive lowering of LDL-C levels. Based on these findings, the
      NCEP ATP III revised the LDL-C target from < 100 mg/dL (2.6 mmol/L) to < 70 mg/dL
      (1.8 mmol/L) (optional target) for very high-risk patients and < 130 mg/dL (3.4
      mmol/L) to < 100 mg/dL (2.6 mmol/L) for moderately high-risk patients. For
      patients who fail to achieve their LDL-C target, inhibiting the two main sources
      of cholesterol - synthesis and uptake - can produce more effective lipid
      lowering, allowing more patients to reach their LDL-C goal. Ezetimibe is a highly
      selective inhibitor of cholesterol absorption and simvastatin is an evidence
      based inhibitor of cholesterol synthesis. The LDL-C-lowering efficacy of
      targeting both major sources of cholesterol with ezetimibe plus simvastatin was
      demonstrated in several multicentre, double-blind, placebo-controlled trials in
      patients with hypercholesterolaemia. For patients who do not reach their
      cholesterol goal with a statin, adding ezetimibe 10 mg significantly reduces LDL
      C compared with statin monotherapy. Thus, this treatment option may help patients
      reach the new 'stricter' cholesterol goals. This review, based on a Medline
      database search from January 2000 to August 2005, considers the LDL-C-lowering
      efficacy of ezetimibe and discusses the role of this agent for patients who fail
      to achieve guideline cholesterol goals with statin monotherapy.

PMID- 16574036
TI  - Screening of neuropathic pain components in patients with chronic back pain
      associated with nerve root compression: a prospective observational pilot study
      (MIPORT).
AB  - OBJECTIVE: Chronic back pain is characterized by a combination of neuropathic and
      nociceptive mechanisms of pain generation. The prevalence of the neuropathic pain
      component is unknown. Thus, in the context of an explorative study, we aimed to
      determine the prevalence of signs and symptoms indicating neuropathic pain in
      adult patients treated by orthopaedists. We also aimed to assess the usefulness
      of handheld computers (PDAs) in data collection. METHODS: Prospective
      epidemiological study in 18 orthopaedic practices or centres throughout Germany.
      Physician and patient questionnaires (paper/pencil or on handheld computers,
      PDAs) for patients with back pain of at least 3 months in duration were applied,
      as well as the von Korff score to assess pain intensity (visual analogue scale,
      VAS; 0 = no pain, 10 = worst possible pain) and pain characteristics, the
      Hannover Functional Ability Questionnaire (FFbH-R), and if patients agreed to
      provide information, the short-form Patient Health Questionnaire (PHQ-D) for
      depression. RESULTS: For 717 patients, both patient and physician questionnaires
      were available. Mean patient age was 56 years; pain was predominantly located in
      the low back (87%). Median current pain intensity on the VAS was 5.0. Confirmed
      key signs and symptoms indicated neuropathic pain was frequent, e.g. radicular
      pain radiating beyond the knee towards the foot (40.0%), positive Lasegue sign
      (18.4%), or absent patellar reflex (17.3%). A third of all patients (33.5%) had
      >or=3 characteristic signs for neuropathic pain. Patient functionality was
      severely reduced (median 43.3%). There were no relevant differences in outcomes
      between patients using the paper/pencil method (47%) versus those preferring PDAs
      (53%). CONCLUSION: Screening for neuropathic pain in this setting is feasible
      with simple questionnaires and scales on PDAs. Neuropathic pain is a major
      contributor to chronic back pain and a frequent component in patients seen by
      orthopaedists. At least one third of all patients should undergo additional
      diagnostic measures to confirm the cause of neuropathic pain.

PMID- 16574038
TI  - Outcomes associated with introduction of thiazolidinedione therapy in Medicaid
      enrolled patients with type 2 diabetes: an updated and expanded retrospective
      analysis.
AB  - OBJECTIVES: In an earlier analysis, differences in health-care costs, medication
      adherence, and persistence were examined between patients with type 2 diabetes,
      enrolled in the North Carolina Medicaid, who had newly started thiazolidinedione
      (TZD) therapy and those starting other oral antidiabetic agents. In this
      analysis, the size of the cohort was increased by including 18 months of
      additional Medicaid data (until December 2004) and sought to: (1) replicate the
      results of the original study in a larger cohort; and (2) extend the original
      analysis by providing an additional 18 months of observational follow-up.
      METHODS: A total of 2660 patients newly starting TZD therapy between July 2001
      and December 2003 were compared to 2050 patients starting other oral antidiabetic
      medication for health-care costs and outcomes in the post-medication start year.
      In addition, the initial cohort was followed for an additional 18 months to
      examine if there were any differences in outcomes, such as hospitalization and
      total health-care costs, that could be associated with the type of therapy.
      Multivariate regression techniques, incorporating health-care utilization in the
      year prior to start of new therapy, were used to determine the net cost impact of
      one therapy versus the other. RESULTS: Multiple regression analyses found that
      patients starting TZD have better treatment persistence in the post-medication
      start year compared to patients starting other oral antidiabetic agents (4%
      increase in therapy persistence index, p < 0.001). In addition, patients starting
      TZDs had 18.9% lower total annual health-care costs (p < 0.01) compared to
      patients starting other oral antidiabetic agents. Examination of the original
      cohort of 3191 patients, for up to an additional 18 months, showed TZD's
      association with improved adherence rates but not with persistence. Importantly,
      treatment adherence remained the strongest independent predictor of decreased
      hospitalization risk and health-care cost reduction in this population.
      CONCLUSIONS: Introduction of thiazolidinedione therapy in a Medicaid-enrolled
      type 2 diabetic population was associated with significantly greater treatment
      adherence, in the post-start year, compared to patients starting other oral
      antidiabetic agents.

PMID- 16574037
TI  - Treatment of chronic moderate-to-severe non-malignant pain with polymer-coated
      extended-release morphine sulfate capsules.
AB  - OBJECTIVE: To demonstrate the efficacy and tolerability of polymer-coated
      extended-release morphine sulfate (P-ERMS)(KADIAN) for the treatment of chronic,
      moderate-to-severe, non-malignant pain in a community-based outpatient population
      not satisfactorily relieved with their current therapies. DESIGN: Phase IV,
      prospective, randomized, open-label, blinded endpoint. PARTICIPANTS: Adults (N =
      1428) with chronic, moderate-to-severe, non-malignant pain with visual numeric
      scale scores >or= 4 (0 = no pain; 10 = worst pain). INTERVENTIONS: Patients were
      randomized to P-ERMS once daily in AM or PM for a 4-week treatment period. Dose
      increases were allowed; however, switching to twice-daily dosing was reserved
      until week 2. MAIN OUTCOME MEASURES: Improvement from baseline in pain and sleep
      scales (0-10) (after weeks 2 and 4), quality of life (physical and mental
      component summary scores of the SF-36v2 Health Survey) (week 4), and patient
      (weeks 2 and 4) and clinician (week 4) assessments of current therapy (-4 to +4).
      Patient satisfaction was assessed again 1 month after the study. RESULTS:
      Approximately 70% of patients completed the study, with 2.4% (n = 34)
      discontinuing due to lack of efficacy, and 9.6% (n = 136) discontinuing due to an
      adverse event. Improvements were seen in pain and sleep scores, physical and
      mental component scores of the SF-36v2, and patient and clinician global
      assessment scores (p < 0.0001, all assessments). Patients attained similar
      results regardless of AM vs. PM dosing. More than half (55.4%) of patients were
      maintained on once-daily therapy, with the remainder on a twice-daily regimen, in
      accordance with the prescribing information. Most adverse events (71.6%) were
      mild to moderate in severity, the most common being constipation (11.6%) and
      nausea (9.2%). One-month follow-up indicated continued satisfaction with P-ERMS
      vs. previous medication (p < 0.0001). CONCLUSIONS: P-ERMS was efficacious and
      well tolerated in patients with chronic, moderate-to-severe, non-malignant pain
      when used once or twice daily.

PMID- 16574039
TI  - A review of the benefit-risk profile of gefitinib in Asian patients with advanced
      non-small-cell lung cancer.
AB  - BACKGROUND: Improvements in first-line therapy of advanced non-small-cell lung
      cancer (NSCLC) have increased the need for effective second-line treatment
      options. In a Phase II trial of the anticancer drug gefitinib (IRESSA), greater
      efficacy was observed in Japanese compared with non-Japanese patients.
      Furthermore, results from a placebo-controlled Phase III trial (IRESSA Survival
      Evaluation in Lung cancer [ISEL]) showed that treatment with gefitinib was not
      associated with a statistically significant improvement in survival in either the
      overall or adenocarcinoma co-primary populations, although there was marked
      heterogeneity in survival outcomes between patient groups, with patients of Asian
      origin achieving a significant survival benefit with gefitinib compared with
      placebo. OBJECTIVE: To review the benefit:risk profile of gefitinib in Asian
      patients with advanced NSCLC. RESEARCH DESIGN AND METHODS: We identified and
      reviewed 31 reports (each with >or= 25 patients) of clinical experience with
      gefitinib 250 mg/day in Asia involving a total of > 2000 patients with refractory
      NSCLC in Japan, China, Korea and Taiwan by searching EMBASE and Medline databases
      for publications between 1 January 2003 and 1 July 2005. RESULTS AND DISCUSSION:
      In the majority of these reports, objective response rates of > 25% and disease
      control rates of > 60% have been described. Treatment with gefitinib resulted in
      a median time to progression of > 3 months and a median survival time of > 6
      months in most studies. These 31 reports also demonstrated the efficacy of
      gefitinib in patients with secondary brain metastases, those with poor
      performance status (PS) and in patients receiving the drug as first-line
      treatment. Female gender, adenocarcinoma histology, non-smoking history, good PS
      and the presence of multiple lung metastases are associated with improved
      responsiveness to gefitinib. Reflecting the results of previous clinical trials,
      the reports indicate that gefitinib is generally well tolerated by Asian
      patients. The incidence of interstitial lung disease appears to be higher in
      Japanese than non-Japanese patients, although the reasons for this are not clear.
      Recent findings regarding cellular and genetic factors that may underlie the
      increased responsiveness to gefitinib among Asian patients are discussed.

PMID- 16574040
TI  - Counting the costs of overweight and obesity: modeling clinical and cost
      outcomes.
AB  - OBJECTIVE: To quantify changes in clinical and cost outcomes associated with
      increasing levels of body mass index (BMI) in a US setting. RESEARCH METHODS AND
      PROCEDURES: A semi-Markov model was developed to project and compare life
      expectancy (LE), quality-adjusted life expectancy (QALE) and direct medical costs
      associated with distinct levels of BMI in simulated adult cohorts over a lifetime
      horizon. Cohort definitions included age (20-65 years), gender, race, and BMI (24
      45 kg m(-2)). Cohorts were exclusively male or female and either Caucasian or
      African-American. Mortality rates were adjusted according to these factors using
      published data. BMI progression over time was modeled. BMI-dependent US direct
      medical costs were derived from published sources and inflated to year 2004
      values. A third party reimbursement perspective was taken. QALE and costs were
      discounted at 3% per annum. RESULTS: In young Caucasian cohorts LE decreased as
      BMI increased. However, in older Caucasian cohorts the BMI associated with
      greatest longevity was higher than 25 kg m(-2). A similar pattern was observed in
      young adult African-American cohorts. A survival paradox was projected in older
      African-American cohorts, with some BMI levels in the obese category associated
      with greatest longevity. QALE in all four race/gender cohorts followed similar
      patterns to LE. Sensitivity analyses demonstrated that simulating BMI progression
      over time had an important impact on results. Direct costs in all four cohorts
      increased with BMI, with a few exceptions. CONCLUSIONS: Optimal BMI, in terms of
      longevity, varied between race/gender cohorts and within these cohorts, according
      to age, contributing to the debate over what BMI level or distribution should be
      considered ideal in terms of mortality risk. Simulating BMI progression over time
      had a substantial impact on health outcomes and should be modeled in future
      health economic analyses of overweight and obesity.

PMID- 16574041
TI  - Estimation of symptom-free days in generalized anxiety disorder.
AB  - OBJECTIVE: The efficacy of treatments for generalized anxiety disorder has
      usually been measured in terms of response or remission of symptoms. These
      endpoints, however, may not adequately capture the transient periods of symptom
      abatement and relapse characteristic of chronic psychiatric disorders. Here, we
      evaluate the measurement of treatment effectiveness in terms of the number of
      symptom-free days (SFDs). RESEARCH DESIGN AND METHODS: A pooled analysis was
      performed of data from five manufacturer-initiated trials of venlafaxine extended
      release (XR) in patients with generalized anxiety disorder without co-morbid
      major depressive disorder. The trials were randomized, double-blind, placebo
      controlled and of 8 weeks duration (total intent-to-treat population 1295
      venlafaxine XR, 544 placebo). Two of the studies had extensions up to 6 months
      (intent-to-treat population 514 venlafaxine XR, 253 placebo). The patients were
      >or= 18 years of age with a Hamilton Rating Scale for Anxiety (HAM-A) score of
      >or= 18. MAIN OUTCOME MEASURES: SFDs were estimated using weekly scores on the
      HAM-A. Values of 7 and 0 SFDs, respectively, were assigned to each week the
      patient had a HAM-A score of <or= 7 (the remission threshold) and >or= 18 (the
      minimum threshold for anxiety). Fractional SFD values were assigned
      proportionately to weekly HAM-A scores between 7 and 18. RESULTS: The median
      (inter-quartile range) SFDs were 19 (2-36) for venlafaxine XR and 10 (0-27) for
      placebo in the 8-week studies (p < 0.0001). In the 6-month extension studies the
      SFDs were 102 (27-139) for venlafaxine XR and 36 (0-94) for placebo (p < 0.0001).
      CONCLUSIONS: SFDs differentiate between active treatment and placebo in clinical
      trials and may be an appropriate measure of treatment effectiveness.

PMID- 16574042
TI  - Mobilization versus immobilization in the treatment of acute proximal deep venous
      thrombosis: a prospective, randomized, open, multicentre trial.
AB  - OBJECTIVE: The aim of prescribing strict bed rest for acute deep venous
      thrombosis is to reduce the risk of pulmonary embolism and pain in the legs, as
      well as swelling. This study was performed in order to compare outcome of
      mobilization against 5 days of strict bed rest in patients with acute proximal
      deep venous thrombosis (DVT). METHODS: 103 in-patients with proximal DVT or
      patients admitted to the hospital because of proximal DVT were recruited to a
      randomized study. All patients were treated in hospital and given a lower leg and
      thigh compression bandage as well as therapeutic doses of the low molecular
      weight heparin, dalteparin-sodium (Fragmin). RESULTS: Seven of 52 patients
      (13.5%) in the mobile group versus 14 of 50 patients (28.0%) in the immobile
      group suffered at least one of the outcomes defined under the combined primary
      endpoint (clinically relevant pulmonary embolisms, pulmonary embolisms detectable
      by scintigraphy or computer tomography, progression of thrombosis or new
      thrombosis, nosocomial infections and/or serious adverse events) (p = 0.088),
      whereby serious adverse events occurred once in the mobile group and three times
      in the immobile group. New pulmonary embolisms over the course were seen in 10 of
      50 patients (20%) with a perfusion disorder at baseline scintigraphy, while such
      was ascertained only in one of 52 patients (1.9%) without a perfusion disorder at
      baseline scintigraphy. Leg pain was reduced from 54.1 (+/-30.4) to 20.7 (+/-19.2)
      in the mobilized group and from 41.0 (+/-26.8) to 14.0 (+/-11.1) in the
      immobilized patients. Leg pain was assessed using the visual analogue scale (0 =
      no pain, 100 = maximum pain). More immobilized patients complained of increasing
      back pain (23% versus 6%) and disturbed micturition (10% versus 2%) as well as
      defecation (13% versus 6%) on day 5. More patients in the mobile group reported
      increased stress from the thrombosis and its treatment (15% versus 6%).
      CONCLUSIONS: No benefit of prescribing bed rest in patients with deep venous
      thrombosis could be detected in this study. Based on data available, strict bed
      rest for at least 5 days is not justified if adequate therapy with low molecular
      weight heparin and adequate compression is assured. It remains open whether
      patients with initial signs of pulmonary embolism might profit from a brief
      immobilization.

PMID- 16574043
TI  - Pharmaceutical quality of generic isotretinoin products, compared with
      Roaccutane.
AB  - BACKGROUND: Isotretinoin is the drug of choice for the management of severe
      recalcitrant nodular acne. Several generic products are available. However, their
      pharmaceutical quality, in particular particle size distribution, which may
      affect safety and efficacy is unknown. Hence, prescribing of some generic
      products may be problematic. OBJECTIVES: To assess the pharmaceutical quality of
      14 generic isotretinoin products compared with Roaccutane (F. Hoffmann-La Roche
      Ltd). RESEARCH DESIGN AND METHODS: Tests were performed according to Roche
      standard procedures, European and US pharmacopoeia specifications. Tests included
      isotretinoin content, identity and amount of impurities and degradation products,
      effect of accelerated shelf-life studies on stability, particle size distribution
      and composition of non-active ingredients. RESULTS: The 14 isotretinoin products
      differed by 30-fold in median particle size and showed variation in their non
      active ingredients. The average isotretinoin content of Acnotin and Acne-Tretin
      fell outside the 95-105% Roche specifications. Following accelerated shelf-life
      tests, only four products retained isotretinoin content within Roche
      specifications, whilst Acne-Tretin (the only powder formulation) lost 72.5%
      isotretinoin content. Two generic products exceeded the +/- 2% specification (Ph.
      Eur.) and a further three exceeded the +/- 1% (USP) for tretinoin content, eight
      exceeded the 2.54% specification for total impurities and six contained >or= 5
      unknown impurities. Isotretinoin-5.6-epoxide content exceeded the 1.04%
      specification in five generic products. CONCLUSIONS: Thirteen generic products
      failed to match Roaccutane in one or more tests and 11 failed in three or more
      tests. It cannot be assumed that all generic isotretinoin products are as
      therapeutically effective or safe as Roaccutane.

PMID- 16574044
TI  - Fibrates in the prevention of cardiovascular disease in patients with type 2
      diabetes mellitus: meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: To assess the impact of lipid lowering treatment with fibrates on
      cardiovascular endpoints in patients with type 2 diabetes mellitus. METHODS:
      MEDLINE (from inception to November 2005) and the Cochrane Controlled Trials
      Register (including Issue 3, 2005) were searched for randomised controlled trials
      comparing therapy with fibrates to placebo in patients with type 2 diabetes
      mellitus. Electronic searches were supplemented by manual searching of reference
      lists, reviews, conference abstracts and specialist journals. Incidence rate
      ratios (IRRs) were estimated using a fixed effects model. The primary endpoint
      was the IRR for coronary heart disease (CHD) events (a combination of non fatal
      myocardial infarction and death due to CHD). Secondary endpoints included: (1)
      death due to CHD; (2) fatal and non fatal myocardial infarction; and (3) fatal
      and non fatal stroke. RESULTS: Eight trials and 12 249 patients with type 2
      diabetes were included in the analyses. A total of 924 CHD events (418 and 506 in
      the treatment and placebo groups, respectively) occurred during a follow up of 60
      395 person-years (30 106 and 30 289 in treatment and placebo groups). The
      combined IRR for CHD events was 0.84 (95% confidence interval [CI] 0.74-0.96, p =
      0.008). The numbers needed to treat (NNTs) to prevent one CHD event over 10 years
      were nine and 26 for patients with and without pre-existing CHD, respectively.
      IRRs for death due to CHD, myocardial infarction and stroke were 0.96 (95% CI
      0.77-1.20, p = 0.73), 0.88 (95% CI 0.69-1.12, p = 0.30) and 0.87 (95% CI 0.73
      1.05, p = 0.14), respectively. Larger benefits were found when restricting the
      analysis to trials that were not confounded by unequal provision of additional
      lipid-lowering therapy. CONCLUSIONS: Fibrates are associated with a substantial
      reduction of CHD events, but their exact role in lipid lowering treatment of
      patients with type 2 diabetes mellitus remains to be defined.

PMID- 16574045
TI  - Validating crash locations for quantitative spatial analysis: a GIS-based
      approach.
AB  - In this paper, the spatial variables of the crash database in Hong Kong from 1993
      to 2004 are validated. The proposed spatial data validation system makes use of
      three databases (the crash, road network and district board databases) and relies
      on GIS to carry out most of the validation steps so that the human resource
      required for manually checking the accuracy of the spatial data can be enormously
      reduced. With the GIS-based spatial data validation system, it was found that
      about 65-80% of the police crash records from 1993 to 2004 had correct road names
      and district board information. In 2004, the police crash database contained
      about 12.7% mistakes for road names and 9.7% mistakes for district boards. The
      situation was broadly comparable to the United Kingdom. However, the results also
      suggest that safety researchers should carefully validate spatial data in the
      crash database before scientific analysis.

PMID- 16574046
TI  - Preventing cannabis users from driving under the influence of cannabis.
AB  - Face-to-face, structured interviews were conducted with 320 recent cannabis users
      in New South Wales, Australia to assess the likely deterrent effects of (a)
      increasing the certainty of apprehension for driving under the influence of
      cannabis (DUIC) and (b) doubling the severity of penalties for DUIC. Participants
      were presented with a drug-driving scenario and asked to indicate their
      likelihood of driving given that scenario. The perceived risk of apprehension and
      severity of punishment were manipulated in each scenario to create four different
      certainty/severity conditions and participants were randomly allocated to one of
      these four groups. A subsidiary aim was to assess the likely impact of providing
      factual information about the accident risk associated with DUIC. Recent drug
      drivers who felt at low risk of accident when DUIC were asked to rate their
      willingness to drive if convinced that it was dangerous. The results suggested
      that increasing the certainty but not severity of punishment would produce
      reductions in cannabis-intoxicated driving among recent cannabis users. Providing
      factual information about the risks associated with DUIC would appear to have
      little impact on drug-driving rates among this population.

PMID- 16574047
TI  - Unintentional home injuries reported by an emergency-based surveillance system:
      incidence, hospitalisation rate and mortality.
AB  - OBJECTIVE: The aim of this study is to quantify the incidence of home injuries
      using an integrated surveillance system. It aims to estimate home accident
      mortality. MATERIAL AND METHODS: The sources of data for this epidemiological
      descriptive study were the emergency information system, the hospital information
      system and the mortality registry of Lazio Region, 2000-2001. We selected all
      emergency department (ED) visits for unintentional traumas that occurred at home.
      We calculated incidence of ED visits, hospitalisation and mortality rates by sex
      and age. RESULTS: In the year 2000, 145101 persons visited the ED (2700/100000),
      8.1% of whom were then admitted to the hospital. Incidence was higher among
      children and older people. We observed 620 fatalities, a rate of 0.43%. The
      mortality registry reported 1042 deceased, a home accident-related mortality rate
      of 31.1/100000. CONCLUSIONS: Unintentional injuries in the home are a relevant
      public health problem. Since none of the databases used in the study give a
      complete measure of the burden of home injuries, we combined the data from all of
      them to estimate the mortality and the burden of home injuries. Interventions for
      prevention must identify the specific accidents/injuries they are trying to
      reduce in order to focus their intervention on the appropriate population.

PMID- 16574048
TI  - Implicit identification of irrelevant local objects interacts with global/local
      processing of hierarchical stimuli.
AB  - This work aimed at studying interactions between automatic object identification
      and global/local perceptual processing. We designed a paradigm in which
      participants were presented with pairs of hierarchically organized items,
      composed of global forms made up of local forms. Both global and local forms
      could represent either objects or non-objects. Subjects were instructed to detect
      whether the two hierarchical items composing a pair were identical or different.
      In a dissimilar pair, items differed at one level (target level), the other
      level, made of similar forms on both sides, was irrelevant to perform the task.
      We hypothesized that the automatic identification of object could affect the
      global precedence principle defined by Navon. In agreement with our hypothesis,
      we found that when the irrelevant level was made of objects, the global
      precedence effect was reversed. In contrast, the irrelevant level had no effect
      when the target level included only objects, or when the irrelevant level was
      made of non-object, the global precedence principle was being preserved in these
      cases. This interaction is compatible with the existence of two distinct
      processes working in parallel, namely automatic identification and structural
      analysis, that could either interfere or act together for the detection of
      differences.

PMID- 16574049
TI  - Testing the limits of cognitive plasticity in older adults: application to
      attentional control.
AB  - Laboratory based training studies suggest that older adults can benefit from
      training in tasks that tap control aspects of attention. This was further
      explored in the present study in which older and younger adults completed an
      adaptive and individualized dual-task training program. The testing-the-limits
      approach was used [Lindenberger, U., & Baltes, P. B. (1995). Testing-the-limits
      and experimental simulation: Two methods to explicate the role of learning in
      development. Human Development, 38, 349-360.] in order to gain insight into how
      attentional control can be improved in older adults. Results indicated
      substantial improvement in overlapping task performance in both younger and older
      participants suggesting the availability of cognitive plasticity in both age
      groups. Improvement was equivalent among age groups in response speed and
      performance variability but larger in response accuracy for older adults. The
      results suggest that time-sharing skills can be substantially improved in older
      adults.

PMID- 16574051
TI  - Biological aspects of the Trypanosoma cruzi (Dm28c clone) intermediate form,
      between epimastigote and trypomastigote, obtained in modified liver infusion
      tryptose (LIT) medium.
AB  - We describe some biological characteristics of the Trypanosoma cruzi intermediate
      form derived from the transformation of epimastigotes to trypomastigotes obtained
      from cultivation in modified liver infusion tryptose (LIT) medium. The
      ultrastructural analysis of the intermediate forms in this medium showed the
      enlargement of the kinetoplast located adjacent to the flagellate nucleus. Some
      biological characteristics of the intermediate form are similar to
      trypomastigotes and others to epimastigotes. Despite displaying a similar
      trypomastigote surface charge, the intermediate forms, like the epimastigotes,
      are not resistant to complement-mediated lysis. Moreover, the intermediate forms
      are unable to infect cultured fibroblasts cells but develop limited infections in
      macrophages.

PMID- 16574050
TI  - Polyamines as a defense mechanism against lipoperoxidation in Trypanosoma cruzi.
AB  - The polyamines, spermine and spermidine--organic polycations that are absolutely
      required for eukaryotic cell growth--are shown here to function in Trypanosoma
      cruzi epimastigotes, as protectors of membrane lipoperoxidation by reactive
      oxygen species generated either by H2O2/Fe2+ or nifurtimox. In vitro, spermine
      and spermidine inhibited lipoperoxidation in a dose dependent manner. Spermine
      was more efficient than spermidine in its inhibitory effect. Lipid peroxidation
      induced by H2O2 showed an IC50 of 0.55 mM for spermine and 0.9 mM for spermidine
      while an IC50 of 0.8 mM for spermine and 1.5 mM for spermidine were observed when
      lipoperoxidation was elicited by nifurtimox. Likewise in vivo, both exogenously
      added spermine and spermidine or endogenous increase of spermine levels induced
      by phorbol ester, protected against lipoperoxidation and decreased citotoxicity
      provoked by nifurtimox. Putrescine and cadaverine, also present in T. cruzi had
      no effect at all. None of the polyamines had any effect neither on the scavenging
      of superoxide anion nor on the regulation of antioxidant enzymes such as
      superoxide dismutase and peroxidases involved in H2O2 detoxification. Here we
      point out that spermine, by acting as a protector of membrane lipoperoxidation
      might contribute to survival of T. cruzi continuously exposed to oxidative
      stress.

PMID- 16574052
TI  - Spectrophotometric determination of carbinoxamine maleate in pharmaceutical
      formulations by ternary complex formation with Cu(II) and eosin.
AB  - A simple and sensitive spectrophotometric method was developed for the
      determination of carbinoxamine maleate in pharmaceutical formulations. The method
      is based on the formation of a ternary complex, extractable with chloroform,
      between copper(II), eosin, and carbinoxamine maleate. The absorption spectra of
      the ternary complexes shows, under optimum conditions, a maxima at 538 nm, with
      apparent molar absorptive 6.1690 x 10(4) mol(-1) cm(-1), Sandell's sensitives
      6.75 x 10(-3) microg cm(-2), and linearity in the concentration range 0.75-10.0
      microg ml(-1). The method can be achieved with high accuracy (recovery values,
      100 +/- 2%) and precision (with standard deviation 0.029-0.155 and relative
      standard deviation 3.87-1.55%). The method was again successfully applied, with
      high accuracy and good precision, for the determination of carbinoxamine maleate
      in various pharmaceutical formulations (syrup, drops, and tablets).

PMID- 16574053
TI  - The insufficiency of using SYBR green dyes in electrophoretic mobility shift
      assays of liver X receptor proteins.

PMID- 16574054
TI  - Hydrophilic interaction liquid chromatography-electrospray ionization mass
      spectrometry of tetrodotoxin and its analogs.

PMID- 16574055
TI  - A colorimetric method for the assay of ADP-glucose pyrophosphorylase.

PMID- 16574056
TI  - Oligomerization of nitrophorins.
AB  - Rhodnius prolixus is a blood-sucking insect that uses a mixture of nitrophorin
      (NP) proteins to deliver nitric oxide (NO) from the insect saliva to the hosts
      via a ferric heme coordinated to the protein, causing vasodilatation and
      anticoagulation to support their feeding. R. prolixus NPs 1-4 are very similar
      proteins ( approximately 20 kDa) with different NO affinities for stepwise NO
      release triggered by pH increase and histamine binding in hosts. Ultra-high
      resolution X-ray structures of native and mutant NPs and their kinetic analysis
      already have revealed the fundamental steps of NO binding and release. In this
      study, we found that NPs can exist in multiple oligomerization states at higher
      concentrations. The oligomers are characterized by a combination of multiple
      biophysical methods. The intrinsic features of the oligomerization revealed here
      led us to propose that this intensive, moderately pH- and ligand-dependent
      oligomerization of NPs has physiological implications in the facilitation of the
      efficient storage and release of the highly reactive NO in the insect saliva and
      the victim, respectively.

PMID- 16574057
TI  - The simultaneous measurement of nicotinamide adenine dinucleotide and related
      compounds by liquid chromatography/electrospray ionization tandem mass
      spectrometry.
AB  - We have developed a liquid chromatographic-tandem mass spectrometric method that
      is sensitive and specific and that simultaneously measures cellular NAD(+) and
      related compounds. Using this method, NAD(+), NAAD, NMN, NAMN, NAM, NA, ADPR, and
      5'AMP were first separated over a reverse-phase high-performance liquid
      chromatography resin in a mobile ammonium formate-methanol linear gradient. Then
      each compound was ionized at an electrospray source and detected in the positive
      multiple reaction monitoring mode of a triple-quadrupole tandem mass
      spectrometer. We found a good linear response for each NAD(+)-related compound.
      The limits of quantification for NAD(+) and related compounds range from 0.1 to 1
      pmol. The extraction efficiency of NAD(+) and related compounds from mouse
      erythrocytes is between 84 and 114%. The coefficients of variation for the
      analyses are all less than 6%. Using our method, we measured, in a single
      analysis, the amounts of NMN, NAMN, NAD(+), and 5'AMP present in mouse
      erythrocytes. Additionally, this is the first report of a direct determination of
      the amounts of NMN and NAMN present in any type of cell. These results indicate
      that our method sensitively, specifically, and simultaneously measures cellular
      NAD(+) and related compounds.

PMID- 16574058
TI  - [Gastrectomy: median laparotomy or bilateral transverse subcostal incision?].

PMID- 16574059
TI  - Mitochondrial oxidative stress, aging and caloric restriction: the protein and
      methionine connection.
AB  - Caloric restriction (CR) decreases aging rate and mitochondrial ROS (MitROS)
      production and oxidative stress in rat postmitotic tissues. Low levels of these
      parameters are also typical traits of long-lived mammals and birds. However, it
      is not known what dietary components are responsible for these changes during CR.
      It was recently observed that 40% protein restriction without strong CR also
      decreases MitROS generation and oxidative stress. This is interesting because
      protein restriction also increases maximum longevity (although to a lower extent
      than CR) and is a much more practicable intervention for humans than CR.
      Moreover, it was recently found that 80% methionine restriction substituting it
      for l-glutamate in the diet also decreases MitROS generation in rat liver. Thus,
      methionine restriction seems to be responsible for the decrease in ROS production
      observed in caloric restriction. This is interesting because it is known that
      exactly that procedure of methionine restriction also increases maximum
      longevity. Moreover, recent data show that methionine levels in tissue proteins
      negatively correlate with maximum longevity in mammals and birds. All these
      suggest that lowering of methionine levels is involved in the control of
      mitochondrial oxidative stress and vertebrate longevity by at least two different
      mechanisms: decreasing the sensitivity of proteins to oxidative damage, and
      lowering of the rate of ROS generation at mitochondria.

PMID- 16574060
TI  - Cell-penetrating peptides--a brief introduction.

PMID- 16574061
TI  - Effects of phospholipid hydrolysis on the aggregate structure in DPPC/DSPE
      PEG2000 liposome preparations after gel to liquid crystalline phase transition.
AB  - Upon storage of phospholipid liposome samples, lysolipids, fatty acids, and
      glycerol-3-phosphatidylcholine are generated as a result of acid- or base
      catalyzed hydrolysis. Accumulation of hydrolysis products in the liposome
      membrane can induce fusion, leakage, and structural transformations of the
      liposomes, which may be detrimental or beneficial to their performance depending
      on their applications as, e.g., drug delivery devices. We investigated in the
      present study the influence of phospholipid hydrolysis on the aggregate
      morphology of DPPC/DSPE-PEG2000 liposomes after transition of the phospholipid
      membrane from the gel phase to liquid crystalline phase using high performance
      liquid chromatography (HPLC) in combination with static light scattering, dynamic
      light scattering, and cryo-transmission electron microscopy (cryo-TEM). The rates
      of DPPC hydrolysis in DPPC/DSPE-PEG2000 liposomes were investigated at a pH of 2,
      4, or 6.5 and temperatures of 22 degrees C or 4 degrees C. Results indicate that
      following phase transition, severe structural reorganizations occurred in
      liposome samples that were partially hydrolyzed in the gel phase. The most
      prominent effect was an increasing tendency of liposomes to disintegrate into
      membrane discs in accordance with an increasing degree of phospholipid
      hydrolysis. Complete disintegration occurred when DPPC concentrations had
      decreased by, in some cases, as little as 3.6%. After extensive phospholipid
      hydrolysis, liposomes and discs fused to form large bilayer sheets as well as
      other more complex bilayer structures apparently due to a decreased ratio of
      lysolipid to palmitic acid levels in the liposome membrane.

PMID- 16574062
TI  - Factors affecting the performance of different long terminal repeats in the
      retroviral vector.
AB  - The long terminal repeat (LTR) of retrovirus contains the nucleotide sequences
      that control gene expression. Although several different LTRs have been used in
      the context of retroviral vector, the activity of the various LTRs has not yet
      been systematically compared for their level of gene expression. We evaluated the
      effect of four different LTRs on gene expression using luciferase, stem cell
      factor, and enhanced green fluorescence protein as reporter genes. LTRs tested in
      this study were derived from Moloney murine leukemia virus, myeloproliferative
      sarcoma virus, murine stem cell virus, and spleen focus-forming virus. It was
      found that the level of gene expression is affected by not only LTRs but also the
      transgenes and the cell types in which gene expression occurs. Furthermore, the
      presence of other nucleotide sequences such as the internal ribosome entry site
      (IRES)-neo cassette could also significantly affect gene expression. Our results
      suggested that the LTR should be chosen carefully, more or less on an empirical
      basis.

PMID- 16574063
TI  - IL-4 regulates COX-2 and PGE2 production in human non-small cell lung cancer.
AB  - IL-4 is a type 2 cytokine that may mediate pleiotropic effects in the NSCLC
      microenvironment. Here, we investigated whether IL-4 regulates PGE(2) production
      in NSCLC cells. We found that IL-4 inhibited constitutive COX-2 expression and
      PGE(2) production in A427 and H2122 NSCLC cell lines, and also suppressed IL
      1beta-induced COX-2 expression in A549 and RH2 NSCLC cell lines. COX-2 mRNA was
      decreased in response to IL-4, and promoter analysis indicated that IL-4
      inhibited both constitutive and IL-1beta-induced COX-2 transcription. IL-4
      inhibited IL-1beta-stimulated ERK phosphorylation, which may mediate the
      inhibition of IL-1beta-induced COX-2 by IL-4. IL-4 did not modulate additional
      arachidonic acid pathway enzymes mPGES-1 and 15-PGDH, which could potentially be
      responsible for regulating PGE(2) production. Overall, our studies demonstrate
      that IL-4 has the capacity to inhibit COX-2 mRNA transcription in NSCLC cells and
      the inhibition of PGE(2) appears to be predominately COX-2 dependent.

PMID- 16574064
TI  - The C-terminal domain of human insulin degrading enzyme is required for
      dimerization and substrate recognition.
AB  - Insulin degrading enzyme (IDE), a zinc metalloprotease, can specifically
      recognize and degrade insulin, as well as several amyloidogenic peptides such as
      amyloid beta (Abeta) and amylin. The disruption of IDE function in rodents leads
      to glucose intolerance and cerebral Abeta accumulation, hallmarks of type 2
      diabetes and Alzheimer's disease, respectively. Using limited proteolysis, we
      found that human IDE (113kDa) can be subdivided into two roughly equal sized
      domains, IDE-N and IDE-C. Oligomerization plays a key role in the activity of
      IDE. Size-exclusion chromatography and sedimentation velocity experiments
      indicate that IDE-N is a monomer and IDE-C serves to oligomerize IDE-N. IDE-C
      alone does not have catalytic activity. It is IDE-N that contains the crucial
      catalytic residues, however IDE-N alone has only 2% of the catalytic activity of
      wild type IDE. By complexing IDE-C with IDE-N, the activity of IDE-N can be
      restored to approximately 30% that of wild type IDE. Fluorescence polarization
      assays using labeled insulin reveal that IDE-N has reduced affinity to insulin
      relative to wild type IDE. Together, our data reveal the modular nature of IDE.
      IDE-N is the catalytic domain and IDE-C facilitates substrate recognition as well
      as plays a key role in the oligomerization of IDE.

PMID- 16574065
TI  - Lentiviral siRNA silencing of sphingosine-1-phosphate receptors S1P1 and S1P2 in
      smooth muscle.
AB  - Sphingosine-1-phosphate regulates diverse biological processes through five
      receptor types, S1P(1-5). Two or more S1P receptors are usually co-expressed on
      target cells. We have previously shown that smooth muscle cells of the gut co
      express S1P(1) and S1P(2) receptors that could mediate distinct functions. In the
      absence of selective agonists and antagonists, we developed siRNA constructs to
      silence each receptor separately. The constructs were based on identical
      sequences in several mammalian species. A lentiviral vector-based system was used
      to deliver siRNA into HEK293T cells and smooth muscle cells. One S1P(1) and two
      S1P(2) siRNA constructs specifically inhibited ectopic expression of S1P(1) and
      S1P(2) receptors, respectively, as determined by immunocytochemistry and Western
      blot, and endogenous expression of S1P(1) and S1P(2) receptors in smooth muscle
      cells, as determined by RT-PCR. Measurement of PLC-beta and Rho kinase
      activities, which mediate initial and sustained muscle contraction, confirmed
      receptor silencing and showed that contraction is mediated exclusively by S1P(2)
      receptors.

PMID- 16574066
TI  - Transcriptional up-regulation of restin by all-trans retinoic acid through STAT1
      in cancer cell differentiation process.
AB  - RESTIN, a member of the melanoma-associated antigen superfamily, is a nuclear
      protein induced by atRA (all-trans retinoic acid) in HL60 cells. HeLa cells
      stably transfected with restin results in G1 cell cycle arrest. How this gene is
      regulated by atRA in the cell differentiation process is still unclear. In this
      study, we observed that up-regulation of restin was present during the atRA
      induced HL60 cell differentiation process, suggesting the functional relevance
      between RESTIN and atRA-induced cellular effects. In order to further define the
      transcriptional regulation of restin by atRA, we analyzed the promoter region of
      restin. About 2.1kb 5' flanking sequence of this gene was cloned into vector pGL3
      and its core promoter region was identified through systemic deletions.
      Interestingly, restin promoter containing several potential consensus-binding
      sites of STAT-1alpha was activated by atRA in ER(+) MCF-7 cells but not in ER(-)
      MDA-MB-231 cells, over-expression of STAT-1alpha in latter rescued the activation
      effect of restin promoter in response to atRA and IFNgamma. Our evidence
      supported that STAT-1alpha plays an important role in the atRA-induced
      transcriptional up-regulation of restin, which was associated with the atRA
      induced HL60 cell differentiation and potentially mediated the downstream effects
      of atRA signal pathway via STAT-1alpha in some cancer cells.

PMID- 16574067
TI  - Adult rat bone marrow stromal cells express genes associated with dopamine
      neurons.
AB  - An intensive search is underway to identify candidates to replace the cells that
      degenerate in Parkinson's disease (PD). To date, no suitable substitute has been
      found. We have recently found that adult rat bone marrow stromal cells (MSCs) can
      be induced to assume a neuronal phenotype in vitro. These findings may have
      particular relevance to the treatment of PD. We now report that adult MSCs
      express multiple dopaminergic genes, suggesting that they are potential
      candidates for cell therapy. Using RT-PCR, we have examined families of genes
      that are associated with the development and/or survival of dopaminergic neurons.
      MSCs transcribe a variety of dopaminergic genes including patched and smoothened
      (components of the Shh receptor), Gli-1 (downstream mediator of Shh), and Otx-1,
      a gene associated with formation of the mesencephalon during development.
      Furthermore, Shh treatment elicits a 1.5-fold increase in DNA synthesis in
      cultured MSCs, suggesting the presence of a functional Shh receptor complex. We
      have also found that MSCs transcribe and translate Nurr-1, a nuclear receptor
      essential for the development of dopamine neurons. In addition, MSCs express a
      variety of growth factor receptors including the glycosyl-phosphatidylinositol
      anchored ligand-binding subunit of the GDNF receptor, GFRalpha1, as well as
      fibroblast growth factor receptors one and four. The expression of genes that are
      associated with the development and survival of dopamine neurons suggests a
      potential role for these cells in the treatment of Parkinson's disease.

PMID- 16574068
TI  - A cotton dehydration responsive element binding protein functions as a
      transcriptional repressor of DRE-mediated gene expression.
AB  - Dehydration responsive element binding proteins (DBPs) are members of a larger
      family of transcription factors that are specific to plants and play an important
      role in enhancing plant tolerance to environmental stresses such as drought,
      cold, and high salinity. To gain a better understanding of this type of protein,
      we reported here a novel DBP protein which functioned as a repressor of
      transcriptional in tobacco leaf cells. GhDBP1 was preferentially localized to the
      nucleus of onion epidermis cells and bound specifically to DRE (core sequence,
      A/GCCGAC) in vitro. In addition, RNA gel-blot analysis showed that expression of
      the GhDBP1 gene was mainly induced under osmotic stresses conditions such as
      drought and high salinity. These findings suggest that GhDBP1 can function as a
      transcriptional repressor for DRE element-mediated gene expression and provides
      an important insight into the molecular adaptation mechanisms of environmental
      stresses in cotton plants.

PMID- 16574069
TI  - hnulp1, a basic helix-loop-helix protein with a novel transcriptional repressive
      domain, inhibits transcriptional activity of serum response factor.
AB  - Many bHLH proteins are involved in cardiac development and cardiovascular
      diseases. Herein, we identified and characterized the human homologue (hnulp1) of
      mouse gene nulp1. The predicted protein contains a bHLH domain and a DUF654
      domain in N-terminal and C-terminal, respectively. Northern blot analysis shows
      that a 2.3-kb transcript expressed broadly in early human embryonic and adult
      tissues, especially with a higher level in adult heart. hnulp1 is a transcription
      repressor when fused to GAL4 DNA-binding domain and co-transfected with VP-16, in
      which DUF654 motif represents the basal transcriptional repressive activity.
      Treatment of cells with trichostatin A can relieve this repression, suggesting
      that the DUF654 motif acts through increasing deacetylase activity at the GAL4
      driven promoter. Overexpression of hnulp1 protein in COS-7 cells inhibits the
      transcriptional activity of serum response factor (SRF), suggesting that hnulp1
      may act as a novel bHLH transcriptional repressor in SRF signaling pathway to
      mediate cellular functions.

PMID- 16574070
TI  - Carbon monoxide mediates heme oxygenase 1 induction via Nrf2 activation in
      hepatoma cells.
AB  - Carbon monoxide (CO) and nitric oxide (NO) are two gas molecules which have
      cytoprotective functions against oxidative stress and inflammatory responses in
      many cell types. Currently, it is known that NO produced by nitric oxide synthase
      (NOS) induces heme oxygenase 1 (HO1) expression and CO produced by the HO1
      inhibits inducible NOS expression. Here, we first show CO-mediated HO1 induction
      and its possible mechanism in human hepatocytes. Exposure of HepG2 cells or
      primary hepatocytes to CO resulted in dramatic induction of HO1 in dose- and time
      dependent manner. The CO-mediated HO1 induction was abolished by MAP kinase
      inhibitors (MAPKs) but not affected by inhibitors of PI3 kinase or NF-kappaB. In
      addition, CO induced the nuclear translocation and accumulation of Nrf2, which
      suppressed by MAPKs inhibitors. Taken together, we suggest that CO induces Nrf2
      activation via MAPKs signaling pathways, thereby resulting in HO1 expression in
      HepG2 cells.

PMID- 16574071
TI  - A fifth protein subunit Ph1496p elevates the optimum temperature for the
      ribonuclease P activity from Pyrococcus horikoshii OT3.
AB  - Ribonuclease P (RNase P) is a ribonucleoprotein complex involved in the
      processing of the 5' leader sequence of precursor tRNA. We previously found that
      the reconstituted particle (RP) composed of RNase P RNA and four proteins
      (Ph1481p, Ph1601p, Ph1771p, and Ph1877p) in the hyperthermophilic archaeon
      Pyrococcus horikoshii OT3 exhibited the RNase P activity, but had a lower optimal
      temperature (around at 55 degrees C), as compared with 70 degrees C of the
      authentic RNase P from P. horikoshii [Kouzuma et al., Biochem. Biophys. Res.
      Commun. 306 (2003) 666-673]. In the present study, we found that addition of a
      fifth protein Ph1496p, a putative ribosomal protein L7Ae, to RP specifically
      elevated the optimum temperature to about 70 degrees C comparable to that of the
      authentic RNase P. Characterization using gel shift assay and chemical probing
      localized Ph1496p binding sites on two stem-loop structures encompassing
      nucleotides A116-G201 and G229-C276 in P. horikoshii RNase P RNA. Moreover, the
      crystal structure of Ph1496p was determined at 2.0 A resolution by the molecular
      replacement method using ribosomal protein L7Ae from Haloarcula marismortui as a
      search model. Ph1496p comprises five alpha-helices and a four stranded beta
      sheet. The beta-sheet is sandwiched by three helices (alpha1, alpha4, and alpha5)
      at one side and two helices (alpha2 and alpha3) at other side. The archaeal
      ribosomal protein L7Ae is known to be a triple functional protein, serving as a
      protein component in ribosome and ribonucleoprotein complexes, box C/D, and box
      H/ACA. Although we have at present no direct evidence that Ph1496p is a real
      protein component in the P. horikoshii RNase P, the present result may assign an
      RNase P protein to L7Ae as a fourth function.

PMID- 16574072
TI  - Identifying Hfq-binding small RNA targets in Escherichia coli.
AB  - The Hfq-binding small RNAs (sRNAs) have recently drawn much attention as
      regulators of translation in Escherichia coli. We attempt to identify the targets
      of this class of sRNAs in genome scale and gain further insight into the
      complexity of translational regulation induced by Hfq-binding sRNAs. Using a new
      alignment algorithm, most known negatively regulated targets of Hfq-binding sRNAs
      were identified. The results also show several interesting aspects of the
      regulatory function of Hfq-binding sRNAs.

PMID- 16574073
TI  - Mu-calpain is involved in the regulation of TNF-alpha-induced matrix
      metalloproteinase-3 release in a rheumatoid synovial cell line.
AB  - Calpain is secreted by intra-articular synovial cells and degrades the main
      components of cartilage matrix proteins, proteoglycan, and collagen, causing
      cartilage destruction. Matrix metalloproteinase-3 (MMP-3) has also been detected
      in synovial fluid and serum, and is involved in the development and progression
      of rheumatoid arthritis by degradation of the extracellular matrix and cartilage
      destruction. To investigate the relationship between calpain and MMP-3 in
      rheumatic inflammation, we utilized the rheumatic synovial cell line, MH7A. Tumor
      necrosis factor (TNF-alpha) stimulation-induced increased expression of mu
      calpain, m-calpain, and MMP-3 in these cells, as well as the release of calpain
      and MMP-3 into the culture medium. The calpain inhibitors, ALLN (calpain
      inhibitor I) and calpeptin, did not affect the intracellular expression of MMP-3,
      but reduced the secretion of MMP-3 in a concentration-dependent manner. Down
      regulation of mu- but not m-calpain by small interfering RNAs abolished TNF-alpha
      induced MMP-3 release from the synovial cells. These findings suggest that
      calpain, particularly mu-calpain, regulates MMP-3 release by rheumatic synovial
      cells, in addition to exerting its own degradative action on cartilage.

PMID- 16574074
TI  - Characterization of an equine mannose-binding lectin and its roles in disease.
AB  - The mannose-binding lectin (MBL), a pattern recognition serum protein,
      participates in the innate immune system of mammals as an opsonin. In humans, MBL
      plays a key role in first-line host defense against infection during the lag
      period prior to the development of a specific immune response. MBL also activates
      complement via the lectin pathway that requires a MBL-associated serine protease
      2 (MASP-2). Homologues of human MBL (hMBL) have been identified in a variety of
      mammals, fish, and primitive animals such as ascidians. In this study, we report
      that equine MBL (eMBL) has properties that are similar to hMBL. In addition, we
      found low levels of MBL:MASP activity in sick horses compared to healthy horses.
      These results suggest that eMBL is involved in the immune response of the horse
      and that low MBL:MASP activity could be used to monitor immune function and
      clinical outcome.

PMID- 16574075
TI  - Conservation and diversity of ancient hemoglobins in Bacteria.
AB  - A group of single-domain proteins in Bacteria similar to thermoglobin, an oxygen
      avid hemoglobin representative of the ancestral form, reveals the primordial
      structure, function, and evolvability of the family. Conserved residues at
      specific positions function to bind ligand or participate in hydrophobic packing
      of the protein core during protein folding. A potential hydrogen bond network
      consisting of a tyrosine and glutamine residue in the distal ligand-binding site
      of most hemoglobins suggests that the ancestral protein bound oxygen avidly. Two
      divergent hemoglobins with mutations at generally conserved positions contain non
      canonical ligand-binding sites, illustrating plasticity of the fold. One binds
      heme in a manner similar to cytochromes and may represent an evolutionary link to
      the precursor of the hemoglobin fold. Conservation suggests specific biochemical
      properties of the ancestral protein; diversity suggests an evolvability of this
      group of hemoglobins tolerant of mutations that perturb conserved biochemical
      properties for adaptation to novel functions.

PMID- 16574076
TI  - Correspondence regarding Ballana et al., "Mitochondrial 12S rRNA gene mutations
      affect RNA secondary structure and lead to variable penetrance in hearing
      impairment".
AB  - Ballana et al. [E. Ballana, E. Morales, R. Rabionet, B. Montserrat, M. Ventayol,
      O. Bravo, P. Gasparini, X. Estivill, Mitochondrial 12S rRNA gene mutations affect
      RNA secondary structure and lead to variable penetrance in hearing impairment,
      Biochem. Biophys. Res. Commun. 341 (2006) 950-957] detected a T1291C mutation
      segregating in a Cuban pedigree with hearing impairment. They interpreted it as
      probably pathogenic, based on family history, RNA conformation prediction and its
      absence in a control group of 95 Spanish subjects. We screened a sample of 203
      deaf subjects and 300 hearing controls (110 "European-Brazilians" and 190
      "African-Brazilians") for the mitochondrial mutations A1555G and T1291C. Five
      deaf subjects had the T1291C substitution, three isolated cases and two familial
      cases. In the latter, deafness was paternally inherited or segregated with the
      A1555G mutation. This doesn't support the hypothesis of T1291C mutation being
      pathogenic. Two "African-Brazilian" controls also had the T1291C substitution.
      Six of the seven T1291C-carriers (five deaf and two controls) had mitochondrial
      DNA of African origin, belonging to macrohaplogroup L1/L2. Therefore, these data
      point to T1291C substitution as most probably an African non-pathogenic
      polymorphism.

PMID- 16574077
TI  - Glyoxal markedly compromises hepatocyte resistance to hydrogen peroxide.
AB  - Glyoxal is an interesting endogenous alpha-oxoaldehyde as it originates from
      pathways that have been linked to various pathologies, including lipid
      peroxidation, DNA oxidation and glucose autoxidation. In our previous study we
      showed that the LD(50) of glyoxal towards isolated rat hepatocytes was 5mM.
      However, 10microM glyoxal was sufficient to overcome hepatocyte resistance to
      H(2)O(2)-mediated cytotoxicity. Hepatocyte GSH oxidation, NADPH oxidation,
      reactive oxygen species formation, DNA oxidation, protein carbonylation and loss
      of mitochondrial potential were also markedly increased before cytotoxicity
      ensued. Cytotoxicity was prevented by glyoxal traps, the ferric chelator,
      desferoxamine, and antioxidants such as quercetin and propyl gallate. These
      results suggest there is a powerful relationship between H(2)O(2)-induced
      oxidative stress and glyoxal which involves an inhibition of the NADPH supply by
      glyoxal resulting in cytotoxicity caused by H(2)O(2)-induced mitochondrial
      oxidative stress.

PMID- 16574078
TI  - Neurotensin receptor activation sensitizes to the locomotor stimulant effect of
      cocaine: a role for NMDA receptors.
AB  - This study was aimed at determining whether repeated activation of neurotensin
      receptors sensitizes to cocaine-induced locomotor activity and whether this
      effect can be prevented by blockade of N-methyl-d-aspartate receptors.
      Independent groups of male rats were injected on four occasions, every other day
      (training phase), with vehicle or one of two doses (4 and 8 mg/kg) of the NMDA
      antagonist CPP [(+/-)-3-(2-carboxypiperazine-4-yl)-propanephosphonic)] followed
      by an intracerebroventricular injection of 18 nmol/10 microl of d
      Tyr[(11)]neurotensin, or its vehicle. Ambulatory, non-ambulatory and vertical
      movements were measured for 2 h on every test day. One week after the last day of
      the training phase, locomotor responses to a single injection of cocaine (7.5
      mg/kg, ip) were measured in all rats; a second cocaine challenge test was
      performed 3 weeks post-training. Results show that during the training phase d
      Tyr[(11)]neurotensin produced an initial suppression of all locomotor responses
      followed by an augmentation of ambulatory and non-ambulatory activity compared to
      controls, effects that were only slightly altered by CPP. Cocaine produced higher
      ambulatory and non-ambulatory activity in animals pre-exposed to neurotensin than
      in the vehicle pre-exposed animals, a sensitization effect that was not prevented
      by CPP at 1 week post-training but that was blocked at 3 weeks at the high dose.
      When given alone, the low dose of CPP produced an effect very similar to that of
      neurotensin on cocaine sensitization. These results further confirm that
      neurotensin plays a role in sensitization to psychostimulant drugs and suggests
      that NMDA receptors are involved in the long-term effect of exposure to
      neurotensin.

PMID- 16574079
TI  - Neural activity of inferences during story comprehension.
AB  - In this event-related functional magnetic resonance imaging (fMRI) study,
      participants listened to and comprehended short stories implying or explicitly
      stating inference events. The aim of this study was to examine the neural
      mechanisms that underlie inference generation, a process essential to successful
      comprehension. We observed distinct patterns of increased fMRI signal for implied
      over explicit events at two critical points during the stories: (1) within the
      right superior temporal gyrus when a verb in the text implied the inference; and
      (2) within the left superior temporal gyrus at the coherence break or when
      participants need to generate an inference to understand the story. To find the
      most compelling evidence of neural activity during inference generation, we
      examined fMRI signal at these two critical points separately for people with high
      working memory capacity (i.e., those individuals who are most likely to draw
      inferences during text comprehension). Interestingly, high working memory
      individuals showed greater fMRI signal for implied than explicit events in the
      left inferior frontal gyrus at the coherence break compared to low working memory
      individuals. This present study provides evidence that areas within the superior
      temporal gyrus and inferior frontal gyrus are heavily recruited when individuals
      generate inferences, even during ongoing comprehension that demands many
      cognitive processes. In addition, the data suggest that the right hemisphere
      superior temporal gyrus is particularly involved during early inferential
      processing, whereas the left hemisphere superior temporal gyrus is particularly
      involved during later inferential processing in story comprehension.

PMID- 16574080
TI  - Electrophysiological characterization of substantia nigra dopaminergic neurons in
      partially lesioned rats: effects of subthalamotomy and levodopa treatment.
AB  - Progressive degeneration of dopaminergic neurons in the substantia nigra pars
      compacta is the main histopathological characteristic of Parkinson's disease. We
      studied the electrophysiological characteristics of the spontaneous activity of
      substantia nigra pars compacta dopaminergic neurons in rats with a partial,
      unilateral, 6-hydroxydopamine lesion of the nigrostriatal pathway. In addition,
      the effects of subthalamotomy and prolonged levodopa treatment on the activity of
      dopaminergic neurons were investigated. As a result of the lesion ( approximately
      50% neuronal loss), the number of spontaneously active neurons was significantly
      reduced. Basal firing rate, burst firing and responsiveness to intravenously
      administered apomorphine remained unchanged. In contrast, the variation
      coefficient, a measure of interspike interval regularity, was significantly
      increased. Ibotenic acid (10 microg) lesion of the ipsilateral subthalamic
      nucleus in lesioned rats did not modify the electrophysiological parameters.
      However, prolonged levodopa treatment (100 mg/kg/day + benserazide 25 mg/kg/day,
      14 days) reversed the irregularity observed in cells from lesioned rats, while it
      induced an irregular firing pattern in cells from intact rats. Our results using
      an experimental model of moderate Parkinson's disease indicate that surviving
      substantia nigra pars compacta dopaminergic neurons fire irregularly. In this
      model, subthalamotomy does not modify the firing pattern while levodopa treatment
      efficiently restores normal firing of SNpc neurons and does not appear to be
      toxic to them.

PMID- 16574081
TI  - Prospective contributions of transgenic mouse models to central auditory
      research.
AB  - Neuroscientists are increasingly embracing mice as a means to address central
      nervous system questions at a molecular level. Examples abound from sensory
      systems like olfaction and vision. The use of mice to study central auditory
      processing, however, has remained relatively limited. In this commentary, I draw
      on some of the successes from other fields to highlight directions in which mouse
      models may contribute valuable and otherwise unattainable insights into the
      neural circuitry and plasticity within central auditory stations. Efforts towards
      this are beginning and would benefit from increased collaboration to generate
      useful transgenic mouse models for such studies.

PMID- 16574082
TI  - Polysyllabic pseudo-word processing in reading and lexical decision: converging
      evidence from behavioral data, connectionist simulations and functional MRI.
AB  - The cognitive mechanisms involved in polysyllabic pseudo-word processing -- and
      their neurobiological correlates -- were studied through the analysis of length
      effects on French words and pseudo-words in reading and lexical decision.
      Connectionist simulations conducted on the ACV98 network paralleled the
      behavioral data in showing a strong length effect on naming latencies for pseudo
      words only and the absence of length effect for both words and pseudo-words in
      lexical decision. Length effects in reading were characterized at the
      neurobiological level by a significant and specific activity increase for pseudo
      words as compared to words in the right lingual gyrus (BA 19), the left superior
      parietal lobule and precuneus (BA7), the left middle temporal gyrus (BA21) and
      the left cerebellum. The behavioral results suggest that polysyllabic pseudo-word
      reading mainly relies on an analytic procedure. At the biological level,
      additional activations in visual and visual attentional brain areas during long
      pseudo-word reading emphasize the role of visual and visual attentional processes
      in pseudo-word reading. The present findings place important constraints on
      theories of reading in suggesting the involvement of a serial mechanism based on
      visual attentional processing in pseudo-word reading.

PMID- 16574083
TI  - Minocycline protects PC12 cells against NMDA-induced injury via inhibiting 5
      lipoxygenase activation.
AB  - Recently, we have reported that minocycline, a semi-synthetic tetracycline with
      neuroprotective effects, inhibits the in vitro ischemic-like injury and 5
      lipoxygenase (5-LOX) activation in PC12 cells. In the present study, we further
      determined whether minocycline protects PC12 cells from excitotoxicity via
      inhibiting 5-LOX activation. We used N-methyl-d-aspartate (NMDA, 200 microM) to
      induce early (exposure for 6 h) and delayed (exposure for 6 h followed by 24 h
      recovery) injuries. We found that NMDA receptor antagonist ketamine, 5-LOX
      inhibitor caffeic acid and minocycline concentration dependently attenuated NMDA
      induced early and delayed cell injuries (viability reduction and cell death).
      However, only ketamine (1 microM) inhibited NMDA-evoked elevation of
      intracellular calcium. In addition, immunohistochemical analysis showed that NMDA
      induced 5-LOX translocation to the nuclear membrane after 1- to 6-h exposure
      which was confirmed by Western blotting, indicating that 5-LOX was activated.
      Ketamine, caffeic acid and minocycline (each at 1 microM) inhibited 5-LOX
      translocation after early injury. After delayed injury, PC12 cells were shrunk,
      and 5-LOX was translocated to the nuclei and nuclear membrane; ketamine, caffeic
      acid and minocycline inhibited both cell shrinking and 5-LOX translocation. As a
      control, 12-LOX inhibitor baicalein showed a weak effect on cell viability and
      death, but no effect on 5-LOX translocation. Therefore, we conclude that the
      protective effect of minocycline on NMDA-induced injury is partly mediated by
      inhibiting 5-LOX activation.

PMID- 16574084
TI  - Hippocampal pyramidal cells in adult Fmr1 knockout mice exhibit an immature
      appearing profile of dendritic spines.
AB  - Fragile X syndrome (FXS) is a common form of mental retardation caused by the
      absence of functional fragile X mental retardation protein (FMRP). FXS is
      associated with elevated density and length of dendritic spines, as well as an
      immature-appearing distribution profile of spine morphologies in the neocortex.
      Mice that lack FMRP (Fmr1 knockout mice) exhibit a similar phenotype in the
      neocortex, suggesting that FMRP is important for dendritic spine maturation and
      pruning. Examination of Golgi-stained pyramidal cells in hippocampal subfield CA1
      of adult Fmr1 knockout mice reveals longer spines than controls and a morphology
      profile that, while essentially opposite of that described in the Fmr1 knockout
      neocortex, appears similarly immature. This finding strongly suggests that FMRP
      is required for the processes of spine maturation and pruning in multiple brain
      regions and that the specific pathology depends on the cellular context.

PMID- 16574086
TI  - B cells as antigen presenting cells.
AB  - Several characteristics confer on B cells the ability to present antigen
      efficiently: (1) they can find T cells in secondary lymphoid organs shortly after
      antigen entrance, (2) BCR-mediated endocytosis allows them to concentrate small
      amounts of specific antigen, and (3) BCR signaling and HLA-DO expression direct
      their antigen processing machinery to favor presentation of antigens internalized
      through the BCR. When presenting antigen in a resting state, B cells can induce T
      cell tolerance. On the other hand, activation by antigen and T cell help converts
      them into APC capable of promoting immune responses. Presentation of self
      antigens by B cells is important in the development of autoimmune diseases, while
      presentation of tumor antigens is being used in vaccine strategies to generate
      immunity. Thus, detailed understanding of the antigen presenting function of B
      cells can lead to their use for the generation or inhibition of immune responses.

PMID- 16574085
TI  - Effects of a Na+/Ca2+ exchanger inhibitor on pulmonary vein electrical activity
      and ouabain-induced arrhythmogenicity.
AB  - OBJECTIVE: Pulmonary veins (PVs) are the most important focus for generation of
      atrial fibrillation. The Na(+)/Ca(2+) exchange (NCX) current is important in PV
      electrical activity and cardiac glycosides-induced arrhythmias. The purpose of
      this study was to investigate whether KB-R7943, a NCX current blocker with
      preferential inhibition of the Ca(2+) influx, may alter PV electrophysiological
      characteristics and reduce glycoside-induced arrhythmogenicity. METHODS:
      Conventional microelectrodes were used to record the effects of KB-R7943 on
      action potentials and contractility in isolated rabbit PV tissue specimens with
      and without administration of ouabain. The ionic currents and intracellular
      calcium were studied in isolated single cardiomyocytes before and after KB-R7943
      by the whole-cell patch clamp and indo-1 fluorimetric ratio techniques. RESULTS:
      KB-R7943 (0, 3, 10, 30 microM) concentration-dependently prolonged APD(50) and
      APD(90) and decreased the PV firing rates (2.3 +/- 1.2 Hz, 2.1 +/- 1.2 Hz, 1.9 +/
      0.9 Hz, 1.7 +/- 1.1 Hz, n = 7, p < 0.05) and incidences of delayed
      afterdepolarizations (DADs). KB-R7943 (3, 30 microM) decreased transient inward
      currents, Ca(2+) transient and sarcoplasmic reticulum Ca(2+) content. Ouabain (0,
      0.1, 1 microM) concentration-dependently increased the PV firing rates and DADs
      in PVs with spontaneous activity (n = 7) and induced nonsustained spontaneous
      activity (1 microM) in the PVs without spontaneous activity (n = 14). However, in
      the presence of KB-R7943 (30 microM), ouabain (1 microM) did not increase the PV
      firing rates or induce spontaneous activity in the PVs without spontaneous
      activity (n = 7). CONCLUSIONS: KB-R7943 reduces the PV arrhythmogenic activity
      and prevents the ouabain-induced arrhythmogenicity. Our findings support the role
      of the NCX current in the PV electrical activity.

PMID- 16574087
TI  - The effect of chain length on the melting temperature and size of
      dialkyldimethylammonium bromide vesicles.
AB  - Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were
      used to obtain the gel to liquid-crystalline phase transition temperature (Tm)
      and the apparent hydrodynamic radius (Rh) of spontaneously formed cationic
      vesicles of dialkyldimethylammonium bromide salts (CnH2n+1)2(CH3)2N+.Br-, with
      varying chain lengths. The preparation of cationic vesicles from aqueous solution
      of these surfactants, for n=12, 14, 16 and 18 (DDAB, DTDAB, DHDAB and DODAB,
      respectively), requires the knowledge of the surfactant gel to liquid-crystalline
      phase transition temperature, or melting temperature (Tm) since below this
      temperature these surfactants are poorly or not soluble in water. That series of
      cationic surfactants has been widely investigated as vesicle-forming surfactants,
      although C12 and C18, DDAB and DODAB are by far the most investigated from this
      series. The dependence of Tm of these surfactants on the number n of carbons in
      the surfactant tails is reported. The Tm obtained by DSC increases non-linearly
      with n, and the vesicle apparent radius Rh is about the same for DHDAB and DODAB,
      but much smaller for DDAB.

PMID- 16574088
TI  - Changes in molecular order across the lamellar-to-inverted hexagonal phase
      transition depend on the position of the double-bond in mono-unsaturated
      phospholipid dispersions.
AB  - A series of mono-unsaturated phosphatidylethanolamine (PE) model membranes is
      studied using deuterium nuclear magnetic resonance (NMR) and differential
      scanning calorimetry. As the position of the double bond is systematically
      changed, the internal conformational motions are monitored through the bilayer-to
      inverted-hexagonal phase transition. The order parameter profiles extracted from
      the NMR spectra report on the conformational order of the lipid and on the way
      this order is changed by structural reorganizations of the membrane. The
      calculation of a ratio of renormalized order parameter profiles is presented here
      as an attempt to distill the essential features of these changes into
      dimensionless descriptions of "shape" functions. This variation of the extent of
      molecular disorder along the long molecular axis of the phospholipids appears to
      be a recurring motif, modulated by temperature, structural rearrangement, and
      chemical composition of the membrane. The reported experimentally measured
      changes in the shape of the order parameter profile can be compared to those
      obtained during molecular dynamics simulation studies.

PMID- 16574089
TI  - PCR screening for 22q11.2 microdeletion: development of a new cost-effective
      diagnostic tool.
AB  - BACKGROUND: Del22q11.2 syndrome is the most frequent known chromosomal
      microdeletion syndrome. Previous studies suggest that a substantial number of
      patients with congenital heart disease have a 22q11 deletion. The molecular
      diagnosis of Del22q11.2 is usually made by fluorescence in situ hybridization, an
      expensive and not widely available technique. We developed an efficient and cost
      effective PCR SNP assay designed for the screening of 22q11.2 deletion through
      consecutive homozygosity. METHODS: Through the screening of dbSNP we have
      selected SNP markers located in the 22q11.2 microdeleted region. Population
      heterozygosities were determined in 213 normal individuals. Designed assays
      consisted of PCR amplification followed by restriction enzyme digestion.
      Fragments generated were visualized on agarose gel and genotyped. RESULTS:
      Selected markers were: rs5748411, rs2238778, rs4819523 and rs4680. All selected
      markers were localized in the 22q11.2 deleted region. Allele and genotype
      frequencies of all selected markers were under Hardy-Weinberg equilibrium.
      Selected SNPs were not in linkage disequilibrium. Predicted assay specificity was
      estimated to be 92.86% in the Brazilian population. CONCLUSIONS: The use of
      consecutive homozygosity in this SNP-based diagnostic test may be used as a cost
      effective tool in reference molecular genetics laboratories.

PMID- 16574090
TI  - Development and cross-validation of sequencing-based assays for genotyping common
      polymorphisms of the CXCL5 gene.
AB  - BACKGROUND: Epithelial neutrophil activating peptide (ENA-78) is encoded by the
      polymorphic CXCL5 gene and is a recruiter and activator of neutrophils.
      Furthermore, ENA-78 may be involved in pathological inflammatory processes and
      variable drug responses. METHODS: To facilitate future disease-gene and
      pharmacogenetic investigation of ENA-78, we developed and cross-validated medium-
      to high-throughput genotyping assays for 2 commonly occurring CXCL5 polymorphisms
      (rs352046 and rs425535). Furthermore, we compared allele and genotype frequencies
      in a U.S. population with those of a previously studied European population.
      RESULTS: There was 100% genotype concordance between the 2 methods used
      (Pyrosequencing and TaqMan). Variant allele frequencies for rs352046 were
      consistent between the U.S. (16%) and European (16%) populations, while the
      rs425535 variant allele was more than twice as high in the European cohort (38%
      vs. 16%). There was complete linkage of genotypes at both loci in our population.
      CONCLUSIONS: The distribution of variant alleles for the 2 polymorphisms studied
      should be further evaluated in other populations. In addition, our data highlight
      the importance of assay validation using multiple platforms.

PMID- 16574091
TI  - Re-thinking stages of cognitive development: an appraisal of connectionist models
      of the balance scale task.
AB  - The present paper re-appraises connectionist attempts to explain how human
      cognitive development appears to progress through a series of sequential stages.
      Models of performance on the Piagetian balance scale task are the focus of
      attention. Limitations of these models are discussed and replications and
      extensions to the work are provided via the Cascade-Correlation algorithm. An
      application of multi-group latent class analysis for examining performance of the
      networks is described and these results reveal fundamental functional
      characteristics of the networks. Evidence is provided that strongly suggests that
      the networks are unable to acquire a mastery of torque and, although they do
      recover certain rules of operation that humans do, they also show a propensity to
      acquire rules never previously seen.

PMID- 16574092
TI  - Automatic measure of the split in the second cardiac sound by using the wavelet
      transform technique.
AB  - This paper is concerned with the identification and automatic measure of the
      split in the second heart sound (S2) of the phonocardiogram signal (PCGs) for
      normal or pathological case. The second heart sound S2 consists of two acoustic
      components A2 and P2, the former is due to the closure of the aortic valve and
      the latter is due to the closure of the pulmonary valve. The aortic valve usually
      closes before the pulmonary valve, introducing a time delay known as "split". A
      automatic technique based on the discrete wavelet transform (DWT) and the
      continuous wavelet transform (CWT) is developed in this paper to measure the
      split of the second cardiac sound (S2) for the normal and pathological cases of
      the PCG signals. To quantify the splitting, the two components in S2 (i.e. A2 and
      P2) are identified and, the delay between the two components can be estimated. It
      is shown that the wavelet transform can provide best information and features of
      the split of S2 and the major components (A2 and P2) and consequently aid in
      medical diagnosis.

PMID- 16574093
TI  - Protein cellular localization prediction with Support Vector Machines and
      Decision Trees.
AB  - Many cellular functions are carried out in specific compartments of the cell. The
      prediction of the cellular localization of a protein is thus related to its
      function identification. This paper uses two Machine Learning techniques, Support
      Vector Machines (SVMs) and Decision Trees, in the prediction of the localization
      of proteins from three categories of organisms: gram-positive and gram-negative
      bacteria and fungi. For all categories considered, the localization task has
      multiple classes, which correspond to the possible protein locations. Since SVMs
      are originally designed for the solution of two-class problems, this paper also
      investigates and compares several strategies to extend this technique to perform
      multiclass predictions.

PMID- 16574094
TI  - cis-Regulatory control of cyclophilin, a member of the ETS-DRI skeletogenic gene
      battery in the sea urchin embryo.
AB  - The Strongylocentrotus purpuratus cyclophilin1 gene (Sp-cyp1) is expressed
      exclusively in skeletogenic mesenchyme cells of the embryo, beginning in the
      micromere lineage of the early blastula stage and continuing after gastrulation
      during the syncytial deposition of the skeleton. This gene encodes a protein
      which is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. Sp
      cyp1 is among the differentiation genes activated in the skeletogenic territory
      as a terminal function of the endomesodermal gene regulatory network. Network
      perturbation analysis had predicted the skeletogenic regulators Ets1 and
      Deadringer (Dri) to be its driver inputs. Here, we show that a 218-bp cis
      regulatory DNA fragment recapitulates skeletogenic Sp-cyp1 expression; that
      elimination of either Ets1 or Dri inputs severely depresses the activity of
      expression constructs containing this DNA fragment; and that Ets1 and Dri target
      sites within the 218 bp fragment are required for normal expression. This
      indicates that the predicted inputs are direct. Other studies indicate that the
      same inputs are evidently necessary for expression of several other skeletogenic
      differentiation genes, and these genes probably constitute a skeletogenic gene
      battery, defined by its Ets plus Dri regulatory inputs.

PMID- 16574095
TI  - Sox17 influences the differentiation of respiratory epithelial cells.
AB  - The Sry-related HMG box transcription factor, Sox17, is required for formation of
      definitive endoderm that gives rise to various organs, including thyroid, lung,
      liver, pancreas, and intestine. While expressed at high levels in the embryonic
      endoderm, Sox17 is also expressed in mature tissues, including the lung. Sox17
      expression in respiratory epithelial cells was first detected in the fetal lung
      at embryonic day 18. Thereafter, Sox17 expression was restricted primarily to
      ciliated cells, suggesting its potential role in airway cell differentiation.
      When expressed in epithelial cells of the embryonic lung, Sox17 inhibited
      peripheral epithelial cell differentiation and disrupted branching morphogenesis.
      In vitro, Sox17 inhibited Sftpc and enhanced Foxj1 promoter activity, consistent
      with its expression in proximal airway cells. Conditional expression of Sox17 in
      peripheral respiratory epithelial cells of adult lung induced hyperplastic
      clusters of cells expressing increased levels of beta-catenin and differentiation
      markers representing multiple proximal respiratory epithelial cell types. Sox17
      prolonged survival and enhanced growth and differentiation of respiratory
      epithelial cells in vitro. Sox17 induced plasticity of respiratory epithelial
      cells, reprogramming alveolar cells into epithelial cells with characteristics
      more typical of the proximal airway. Sites of expression and the effects of Sox17
      in vivo and in vitro are consistent with a role for Sox17 or other members of the
      Sox family of transcription factors in differentiation of the conducting airway
      epithelium.

PMID- 16574096
TI  - A robust system for RNA interference in the chicken using a modified microRNA
      operon.
AB  - RNA interference (RNAi) provides an effective method to silence gene expression
      and investigate gene function. However, RNAi tools for the chicken embryo have
      largely been adapted from vectors designed for mammalian cells. Here we present
      plasmid and retroviral RNAi vectors specifically designed for optimal gene
      silencing in chicken cells. The vectors use a chicken U6 promoter to express RNAs
      modelled on microRNA30, which are embedded within chicken microRNA operon
      sequences to ensure optimal Drosha and Dicer processing of transcripts. The
      chicken U6 promoter works significantly better than promoters of mammalian origin
      and in combination with a microRNA operon expression cassette (MOEC), achieves up
      to 90% silencing of target genes. By using a MOEC, we show that it is also
      possible to simultaneously silence two genes with a single vector. The vectors
      express either RFP or GFP markers, allowing simple in vivo tracking of vector
      delivery. Using these plasmids, we demonstrate effective silencing of Pax3, Pax6,
      Nkx2.1, Nkx2.2, Notch1 and Shh in discrete regions of the chicken embryonic
      nervous system. The efficiency and ease of use of this RNAi system paves the way
      for large-scale genetic screens in the chicken embryo.

PMID- 16574097
TI  - Evi1 is specifically expressed in the distal tubule and duct of the Xenopus
      pronephros and plays a role in its formation.
AB  - The ecotropic viral integration site 1 (Evi1) and related MEL1 (MDS1/Evi1-like
      gene 1) genes are zinc finger oncogenic transcription factors involved in myeloid
      leukaemia. Here, we show that in Xenopus, Evi1 and MEL1 have partially
      overlapping restricted embryonic expression profiles. Within the pronephros, Evi1
      and MEL1 are sequentially expressed within the distal tubule and duct
      compartments, Evi1 transcription being detected prior to any sign of pronephric
      morphogenesis. In the pronephros of zebrafish embryos, Evi1 expression is
      restricted to the posterior portion of the duct, the anterior portion having
      characteristics of proximal tubules. In the Xenopus pronephros, Evi1 expression
      is upregulated by retinoid signaling and repressed by overexpression of xWT1 and
      by Notch signaling. Overexpression of Evi1 from late neurula stage specifically
      inhibits the expression of proximal tubule and glomus pronephric markers. We show
      that the first zinc finger and CtBP interaction domains are required for this
      activity. Overexpression of a hormone-inducible Evi1-VP16 antimorphic fusion with
      activation at neurula stage disrupts distal tubule and duct formation and expands
      the expression of glomus markers. Although overexpression of this construct also
      causes in many embryos a reduction of proximal tubule markers, embryos with
      expanded and ectopic staining have been also observed. Together, these data
      indicate that Evi1 plays a role in the proximo-distal patterning of the
      pronephros and suggest that it may do so by functioning as a CtBP dependent
      repressor.

PMID- 16574098
TI  - Effects of flavonoids extracted from Scutellaria baicalensis Georgi on hemin
      nitrite-H2O2 induced liver injury.
AB  - Hemin-nitrite-H2O2 system may play a role in liver oxidative injury in some
      pathological events. In this paper, the effects of the three active components of
      the root of Scutellaria baicalensis Georgi, i.e. baicalin, baicalein and wogonin,
      on hemin-nitrite-H2O2 induced liver injury were studied in liver homogenate,
      liver microsome and human hepatoblastoma cell line HepG2 cells. It was found that
      hemin-nitrite-H2O2 could induce liver homogenate protein nitration, lipid
      peroxidation and liver microsome protein oxidation; it also caused a decrease of
      HepG2 cells viability. Baicalein, baicalin and wogonin could inhibit protein
      nitration and lipid peroxidation in liver homogenate as well as in HepG2 cells in
      a dose-dependent manner, the inhibition order was baicalein>baicalin>>wogonin.
      These three flavonoids also inhibited the oxidation of protein in liver
      microsome, the decrease of cell viability and the content of GSH in HepG2 cells,
      among which baicalin represented the most inhibitory effect. Besides, hemin-H2O2
      induced cell injury could be augmented with the existence of nitrite, indicating
      protein nitration involved in hemin-nitrite-H2O2 induced liver injury. These
      results demonstrated hemin-nitrite-H2O2 could induce liver injury through
      oxidizing or nitrating different biomolecules. Baicalein, baicalin and wogonin
      could inhibit hemin-nitrite-H2O2 induced liver injury in dose-dependent manners
      by inhibiting oxidation and nitration.

PMID- 16574099
TI  - Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on
      development of steatohepatitis in mice fed a methionine- and choline-deficient
      diet.
AB  - We evaluated the effects of bezafibrate, a peroxisome proliferator-activated
      receptor (PPAR) pan-agonist, and GW501516, a PPARdelta agonist, on mice fed a
      methionine- and choline-deficient (MCD) diet, a model of non-alcholic
      steatohepatitis (NASH), to investigate (a) the efficacy of bezafibrate against
      non-alcholic steatohepatitis and (b) the relation between non-alcholic
      steatohepatitis and the functional role of PPARdelta. Bezafibrate (50 or 100
      mg/kg/day) and GW501516 (10 mg/kg/day) were administered by gavage once a day for
      5 weeks. Hepatic lipid contents, plasma triglyceride, high density lipoprotein
      (HDL)-cholesterol and alanine aminotransferase (ALT) concentrations were
      evaluated, as were histopathological changes in the liver and hepatic mRNA
      expression levels. Bezafibrate and GW501516 inhibited the MCD-diet-induced
      elevations of hepatic triglyceride and thiobarbituric acid-reactants contents and
      the histopathological increases in fatty droplets within hepatocytes, liver
      inflammation and number of activated hepatic stellate cells. In this model,
      bezafibrate and GW501516 increased the levels of hepatic mRNAs associated with
      fatty acid beta-oxidation [acyl-CoA oxidase (ACO), carnitine palmitoyltransferase
      1 (CPT-1), liver-fatty acid binding protein (L-FABP) and peroxisomal
      ketothiolase], and reduced the levels of those associated with inflammatory
      cytokines or chemokine [transforming growth factor (TGF)-beta1, interleukin (IL)
      6, IL-1beta, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor
      (TNF) alpha and nuclear factor (NF)-kappaB1]. In addition, bezafibrate
      characteristically reduced the elevation in the level of plasma ALT, but enhanced
      that in plasma adiponectin and increased the mRNA expression levels of its
      receptors (adiponectin receptors 1 and 2). These results suggest that (a)
      bezafibrate (especially) and GW501516 might improve hepatic steatosis via an
      improvement in fatty acid beta-oxidation and a direct prevention of inflammation,
      (b) treatment with a PPARdelta agonist might improve non-alcholic
      steatohepatitis, (c) bezafibrate may improve non-alcholic steatohepatitis via
      activation not only of PPARalpha but also of PPARdelta, because bezafibrate is a
      PPAR pan-agonist.

PMID- 16574101
TI  - Induction of apoptosis and inhibition of telomerase activity by trichostatin A, a
      histone deacetylase inhibitor, in human leukemic U937 cells.
AB  - The objective of the present study was to investigate the effect of trichostatin
      A (TSA), a histone deacetylase (HDAC) inhibitor, on the cell growth and apoptosis
      and its effect on the telomerase activity in human leukemic cell line U937.
      Exposure of U937 cells to TSA resulted in growth inhibition and induction of
      apoptosis in a dose-dependent manner as measured by hemocytometer counts,
      fluorescence microscopy, agarose gel electrophoresis and flow cytometry analysis.
      The increase in apoptosis was associated with the up-regulation in proapoptotic
      Bax expression and down-regulation of antiapoptotic Bcl-2 and Bcl-X(L). TSA
      treatment inhibited the levels of cIAP family members and induced the proteolytic
      activation of caspase-3, which was associated with concomitant degradation of
      poly(ADP-ribose)-polymerase and beta-catenin protein. TSA treatment markedly
      inhibited the activity of telomerase in a dose-dependent fashion. Additionally,
      the expression of human telomerase reverse transcriptase (hTERT), a main
      determinant of the telomerase enzymatic activity, was progressively down
      regulated by TSA treatment. We therefore conclude that TSA demonstrated
      antiproliferative and apoptosis-inducing effects on U937 cells in vitro, and that
      changes in Bcl-2 family protein levels as well as telomerase activity may play an
      important role in its mechanism of action.

PMID- 16574102
TI  - Vascular endothelial growth factor A contributes to glioma-induced migration of
      human marrow stromal cells (hMSC).
AB  - OBJECTIVE: It has been demonstrated that murine neural stem cells (mNSCs) and
      human mesenchymal stroma cells migrate toward experimental gliomas, making stem
      cells a candidate for cellular carrier systems of anti-glioma therapy. However,
      few data are available on the factors involved in regulating stem cell migration.
      The aim of our study was to characterize the migratory and invasive behavior of
      adult human marrow stromal cells (hMSC) that interact with glioma cells,
      especially focusing on vascular endothelial growth factor A (VEGF-A)-mediated
      effects. METHODS: Human MSC were isolated from bone marrow biopsies carried out
      for hematological indications. The chemokinetic activity of hMSC in response to
      glioma-conditioned medium as well as VEGF-A was analyzed using a modified Boyden
      chamber assay. Invasion of hMSC and glioma spheroids was investigated using
      confrontational cultures. To provide analogous data from a well-described system,
      invasion of murine C17.2 neural stem cells was assessed. VEGF-A secretion by
      gliomas and the expression of VEGF-receptor 2 in hMSC were evaluated. RESULTS:
      Human MSC showed an extensive invasion into glioma spheroids. Glioma-conditioned
      medium significantly increased hMSC migration and also invasion, driven by
      chemotaxis. VEGF-A also showed significant pro-migratory and pro-invasive effects
      on hMSC, but in a reduced fashion compared to glioma-conditioned medium.
      CONCLUSIONS: Human MSC show intensive migratory and invasive behavior in the
      presence of glioma cells and glioma-conditioned medium. Among others, VEGF-A
      seems to be one important factor in enhancing and directing stem cell motility.

PMID- 16574103
TI  - Extensive adenosine-to-inosine editing detected in Alu repeats of antisense RNAs
      reveals scarcity of sense-antisense duplex formation.
AB  - One type of RNA editing converts adenosine residues to inosine in double-stranded
      regions. Recent transcriptome analysis has revealed that numerous Alu repeats,
      present within introns and untranslated regions of human transcripts, are subject
      to this A-->I RNA editing. Furthermore, it revealed global transcription of
      antisense RNAs. Here, we demonstrate that antisense RNAs are also edited
      extensively but only in their Alu repeat sequences, and editing does not extend
      to the surrounding sequence. Our findings imply that sense and antisense RNAs
      form two separate intramolecular double-stranded RNAs consisting of inversely
      oriented Alu repeats, but rarely form intermolecular duplexes.

PMID- 16574104
TI  - Membrane topology of the human seipin protein.
AB  - The Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene encodes an
      integral membrane protein, called seipin, of unknown function localized to the
      endoplasmic reticulum of eukaryotic cells. Seipin is associated with the
      heterogeneous genetic disease BSCL2, and mutations in an N-glycosylation motif
      links the protein to two other disorders, autosomal-dominant distal hereditary
      motor neuropathy type V and Silver syndrome. Here, we report a topological study
      of seipin using an in vitro topology mapping assay. Our results suggest that the
      predominant form of seipin is 462 residues long and has an N(cyt)-C(cyt)
      orientation with a long luminal loop between the two transmembrane helices.

PMID- 16574105
TI  - Identification of the basement membrane protein nidogen as a candidate ligand for
      tumor endothelial marker 7 in vitro and in vivo.
AB  - Tumor endothelial marker 7 (TEM7) is a novel transmembrane protein that is highly
      expressed in the tumor endothelium. However, the ligands and functions of TEM7
      are unknown at present. Using a recombinant ectodomain of TEM7 as a probe, we
      could identify the saturable interaction between nidogen and TEM7 in vitro. A
      cell overlay binding assay showed that recombinant nidogen interact with full
      length TEM7 on cell surface. Finally, nidogen/TEM7 interaction enhanced cell
      spreading in TEM7 transfected 293T cells. This novel nidogen/TEM7 interaction may
      provide an important molecular tool with potential therapeutic applications in
      the anti-angiogenic therapies.

PMID- 16574107
TI  - Multiple functions of Notch signaling in self-renewing organs and cancer.
AB  - In recent years a substantial body of evidence has accumulated to support the
      notion that signaling pathways known to be important during embryonic development
      play important roles in regulating self-renewing tissues. Moreover, the same
      pathways are often deregulated during tumorigenesis due to mutations of key
      elements of these pathways. The Notch signaling cascade meets all of the above
      mentioned criteria. We discuss here the pleiotropic roles of the Notch signaling
      pathway in three different self-renewing organs (intestine, hematopoietic system
      and skin) and how its deregulation is involved in tumorigenesis.

PMID- 16574106
TI  - Hcc-2, a novel mammalian ER thioredoxin that is differentially expressed in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver.
      Thus there is great interest to identify novel HCC diagnostic markers for early
      detection of the disease and tumour specific associated proteins as potential
      therapeutic targets in the treatment of HCC. Currently, we are screening for
      early biomarkers as well as studying the development of HCC by identifying the
      differentially expressed proteins of HCC tissues during different stages of
      disease progression. We have isolated, by reverse transcriptase and polymerase
      chain reaction (RT-PCR), a 1741bp cDNA encoding a protein that is differentially
      expressed in HCC. This novel protein was initially identified by proteome
      analysis and we designate it as Hcc-2. The protein is upregulated in poorly
      differentiated HCC but unchanged in well-differentiated HCC. The full-length
      transcript encodes a protein of 363 amino acids that has three thioredoxin (Trx)
      (CGHC) domains and an ER retention signal motif (KDEL). Fluorescence GFP tagging
      to this protein confirmed that it is localized predominantly to the cytoplasm
      when expressed in mammalian cells. Protein alignment analysis shows that it is a
      variant of the TXNDC5 gene, and the human variants found in Genbank all show
      close similarity in protein sequence. Functionally, it exhibits the anticipated
      reductase activity in the insulin disulfide reduction assay, but its other
      biological role in cell function remains to be elucidated. This work demonstrates
      that an integrated proteomics and genomics approach can be a very powerful means
      of discovering potential diagnostic and therapeutic protein targets for cancer
      therapy.

PMID- 16574108
TI  - Mechanisms of signal transduction in photo-stimulated secretion in Phaeocystis
      globosa.
AB  - Phaeocystis globosa, a leading agent in marine carbon cycling, releases its
      photosynthesized biopolymers via regulated exocytosis. Release is elicited by
      blue light and relayed by a characteristic cytosolic Ca(2+) signal. However, the
      source of Ca(2+) in these cells has not been established. The present studies
      indicate that Phaeocystis' secretory granules work as an intracellular Ca(2+)
      oscillator. Optical tomography reveals that photo-stimulation induces InsP(3)
      triggered periodic lumenal [Ca(2+)] oscillations in the granule and corresponding
      out-of-phase cytosolic oscillations of [Ca(2+)] that trigger exocytosis. This
      Ca(2+) dynamics results from an interplay between the intragranular polyanionic
      matrix, and two Ca(2+)-sensitive ion channels located on the granule membrane: an
      InsP(3)-receptor-Ca(2+) channel, and an apamin-sensitive K(+) channel.

PMID- 16574110
TI  - Oxidized protein degradation and repair in ageing and oxidative stress.
AB  - Cellular ageing is characterized by the accumulation of oxidatively modified
      proteins which may be due to increased protein damage and/or decreased
      elimination of oxidized protein. Since the proteasome is in charge of protein
      turnover and removal of oxidized protein, its fate during ageing and upon
      oxidative stress has received special attention, and evidence has been provided
      for an age-related impairment of proteasome function. However, proteins when
      oxidized at the level of sulfur-containing amino acids can also be repaired.
      Therefore, the fate of the methionine sulfoxide reductase system during ageing
      has also been addressed as well as its role in protection against oxidative
      stress.

PMID- 16574109
TI  - Upregulation of hypoxia-induced mitogenic factor in bacterial lipopolysaccharide
      induced acute lung injury.
AB  - Hypoxia-induced mitogenic factor (HIMF), also known as FIZZ1 (found in
      inflammatory zone), plays important roles in lung inflammation. We found that
      intraperitoneal injection of lipopolysaccharide (LPS) induced intensive HIMF
      production exclusively in mouse lung, but not in the heart, liver, spleen or
      kidney. This HIMF production, at least partly, contributes to LPS-induced
      vascular cell adhesion molecule-1 (VCAM-1) upregulation and mononuclear cell
      sequestration to lung parenchyma, while protecting alveolar type II cells from
      LPS-resulted decrease in surfactant protein-C production and cell death. These
      data indicate that HIMF participates in LPS-induced acute lung injury and
      inflammation through modulating VCAM-1 and SP-C expression.

PMID- 16574111
TI  - Cytochrome b(5) is a major reductant in vivo of human indoleamine 2,3-dioxygenase
      expressed in yeast.
AB  - The evolutionary relationship of indoleamine 2,3-dioxygenase (IDO) to some
      gastropod myoglobins suggests that IDO may undergo autoxidation in vivo such that
      one or more currently unidentified electron donors are required to maintain IDO
      heme iron in the active, ferrous state. To evaluate this hypothesis we have used
      yeast knockout mutants in combination with a recently developed yeast growth
      assay for IDO activity in vivo to demonstrate a role for cytochrome b(5) and
      cytochrome b(5) reductase in maintaining IDO activity in vivo.

PMID- 16574112
TI  - Fasting-induced changes of immunological and stress indicators in breeding female
      eiders.
AB  - One adaptive significance of immunosuppression during reproduction can be
      explained by the immunopathology-avoidance hypothesis. This hypothesis states
      that since heat shock proteins (HSP) are highly conserved proteins found in both
      pathogen and host, and are expressed at a higher level during reproduction, the
      risk of autoimmunity is then increased, HSP being the target of the host's immune
      response. Reduced immunocompetence has been attributed to hormonal regulation, in
      particular by glucocorticoids. The current study aimed at testing the
      immunopathology-avoidance hypothesis and the implication of corticosterone in
      incubating fasting common eiders (Somateria mollissima). To this end, we have
      measured immunological and stress indicators including immunoglobulin (IgY),
      HSP70, HSP60, and corticosterone levels in breeding females. A multivariate
      general linear model analysis showed that female body condition, IgY, HSP70, and
      HSP60 levels were the main variables explaining the model. Females showed a
      significant decrease by 15% of their IgY index during incubation. Conversely,
      HSP70 and HSP60 levels significantly increased by 12 and 10%, respectively
      throughout incubation. Moreover, there was a positive significant relationship
      between both HSP whereas HSP60 levels were negatively correlated to IgY index.
      Plasma corticosterone levels showed a tendency to decrease during incubation. We
      conclude that these findings are consistent with the immunopathology-avoidance
      hypothesis in breeding eiders. Nevertheless, the long-term reproductive costs and
      the underlying mechanisms of such an immunosuppression remain to be determined
      and will require further experiments.

PMID- 16574113
TI  - A novel oocyte maturation arresting factor in the central nervous system of
      scallops inhibits serotonin-induced oocyte maturation and spawning of bivalve
      mollusks.
AB  - Serotonin (5-hydroxytriptamine; 5-HT) is a major neurotransmitter that triggers
      oocyte maturation and sequential spawning in bivalve mollusks. A proteinous and
      heat-labile substance that proved to be a novel inhibitor of 5-HT-induced egg
      release from ovarian tissue was found in the cerebral and pedal ganglia (CPG) of
      the scallop Patinopecten yessoensis. The same inhibitory activity was also
      observed in the proteinous fraction from the supernatant of hemolymph.
      Histological observation demonstrated that the novel inhibitor prevented 5-HT
      from inducing oocyte maturation in the scallop ovary and that no prostaglandin
      F2alpha (PGF2alpha) inhibited 5-HT-induced oocyte maturation, although PGF2alpha
      strongly prohibited 5-HT-induced egg release through the gonoduct from ovarian
      tissue. The novel inhibitor from the scallop CPG also prohibited 5-HT-induced
      oocyte maturation of other bivalve species as well as scallops. The novel
      inhibitor, mediated through a receptor mechanism on oocyte membranes, blocked
      extracellular Ca2+ uptake into oocytes, which was observed in 5-HT-induced oocyte
      maturation. It is suggested that the novel inhibitor with a molecular mass of 60
      kDa, named oocyte maturation arresting factor, which appears to be a universal
      substance for bivalve species, may be transported from the CPG to the ovary via
      hemolymph and may prohibit 5-HT-induced oocyte maturation due to the interference
      of extracellular Ca2+ influx into oocytes, eventually resulting in the inhibition
      of spawning. On the other hand, it seems that PGF2alpha inhibits 5-HT-induced
      transport of mature eggs through the gonoduct.

PMID- 16574114
TI  - Testicular development and plasma sex steroid levels in cultured male Senegalese
      sole Solea senegalensis Kaup.
AB  - Testicular development and plasma levels of sex steroids (11-ketotestosterone (11
      KT), testosterone (T) and 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P)) were
      investigated for the first time in cultured male Senegalese sole Solea
      senegalensis. The germ cell dynamics and gonadosomatic index (IG) were monitored.
      Based on the relative abundance of the different types of germ cells present, the
      spermatogenetic cycle was divided into five stages: early (I; spermatogonia
      (SPG)), mid (II; SPG, spermatocytes (SPC) and spermatids (SPD)), and late
      spermatogenesis (III; SPC, SPD, and spermatozoa (SPZ)), functional maturation
      (IV; SPD and SPZ), and recovery (V; SPD, SPZ, and SPG). During summer, fish had
      stage I and V testes and the lowest values in plasma levels of sex steroids and
      IG. Testicular recrudescence seemed to begin in autumn, as denoted by the first
      increase in IG and in the levels of 11-KT and T, and the appearance of testes at
      stage II and III. During winter, the levels of 11-KT and T peaked and soon began
      to decrease, the IG slightly declined and the proportion of running males (RM)
      gradually increased. In spring, levels of 11-KT and T continued to decline, the
      IG slightly increased and the proportion of RM peaked concomitantly with the
      occurrence of stage IV testes. Plasma levels of 17,20beta-P did not change
      significantly throughout testicular development. Transformation of SPD into SPZ
      followed a group-synchronous fashion, a phenomenon which parallels asynchronous
      oocyte development reported in females. This mechanism would be consistent with
      the observed small quantity of sperm that can be manually stripped at any one
      time and other aspects of S. senegalensis reproductive biology.

PMID- 16574115
TI  - Corticosterone metabolism in chicken tissues: evidence for tissue-specific
      distribution of steroid dehydrogenases.
AB  - Glucocorticoids influence the function of numerous tissues. Although there are a
      very large number of studies that have investigated the local metabolism of
      glucocorticoids in mammals, the knowledge of this metabolism in birds is limited.
      The local concentration of corticosterone is critical for both glucocorticoid-
      and mineralocorticoid-dependent activity, and we have therefore carried out
      studies of corticosterone metabolism in various chicken organs. It was found that
      corticosterone was metabolized to 20-dihydrocorticosterone, and in some tissues
      also to 11-dehydrocorticosterone and 11-dehydro-20-dihydrocorticosterone. The
      activity of 20-hydroxysteroid dehydrogenase (20HSD), responsible for the
      transformation of corticosterone to 20-hydroxy derivatives, was abundant in the
      kidney and intestine, with lower levels in the liver and testis. Low levels of
      20HSD were detected in the brain and ovaries. In contrast, 11-hydroxysteroid
      dehydrogenase (11HSD) activity was only found in the kidney and intestine. No
      activity was observed in the brain, testis, or ovaries. The treatment of chickens
      with estrogens stimulated 20HSD activity in the kidney, intestine, and oviduct
      and 11HSD activity in the liver and oviduct. Kinetic studies for corticosterone
      yielded an apparent Km for 11HSD in the nanomolar (Km = 21 +/- 5 nmol.l(-1)) and
      for 20HSD in the micromolar range (Km = 3.7 +/- 0.3 micromol.l(-1)). When
      progesterone or 5alpha-dihydrotestosterone were used instead of corticosterone,
      the tissues reduced the former to 20beta-dihydroprogesterone and the latter to
      both 5alpha,3alpha- and 5alpha,3beta-dihydrotestosterone. The data presents the
      first evidence for corticosterone metabolism via 11beta-, 3alpha/3beta-, and
      20beta-hydroxysteroid dehydrogenases in various chicken organs and provide
      support for the theory of prereceptor modulation of glucocorticoid signals in
      avian tissues.

PMID- 16574116
TI  - Immunohistochemical detection of gonadotropin-like material in the pituitary of
      brown hagfish (Paramyxine atami) correlated with their gonadal functions and
      effect of estrogen treatment.
AB  - Since hagfish are members of the most primitive group of living vertebrates,
      studies on their reproduction are indispensable for understanding phylogenetic
      aspects of vertebrate reproductive system. Nevertheless, our knowledge of the
      reproductive physiology of the hagfish, especially of the pituitary-gonadal axis,
      is almost completely lacking. In the present study, the relationship between the
      amount of immunoreactive gonadotropin (GTH)-like material in the pituitary gland
      and gonadal conditions was examined in the brown hagfish, Paramyxine atami.
      First, pituitary sections were stained immunohistochemically with anti-ovine
      LHbeta, and the degrees of the accumulation of GTH-like material were compared
      among three different groups of gonadal conditions; juveniles and adults with and
      without developing gonads. Immunoreactive GTH-like material was heavily
      accumulated in adults with developing gonads, whereas it was not or only weakly
      accumulated in juveniles or adults without developing gonads. Thus, there was a
      strong positive correlation between the amount of GTH-like material and gonadal
      conditions. Second, effect of estradiol benzoate on GTH-like material was
      examined using three groups of juvenile hagfish: initial control, sham control,
      and experimental animals. Experimental animals received estradiol benzoate
      resolved in sesame oil intraperitoneally every third day for 1 month, whereas
      sham control animals received the same doses of sesame oil. GTH-like material was
      heavily or moderately accumulated in most estrogen-treated animals, whereas it
      was not or weakly accumulated in initial or sham control animals. Thus, estrogen
      treatment in juvenile hagfish resulted in the large increase in the amount of GTH
      like material. From these results, it is suggested the presence of not only GTH
      but also the hypophysial-gonadal feedback system in the hagfish.

PMID- 16574117
TI  - East-West cranial differentiation in pre-Columbian human populations of South
      America.
AB  - South Amerindians are frequently thought of as a rather biologically homogeneous
      megapopulation. However, when native South Americans are assessed by information
      coming from DNA variability analysis, they resolve into two, major distinct
      entities of Eastern and Western zones. The purpose of this study is to
      investigate if the same dual pattern emerges from craniometric data. We
      approached this question by means of functional craniometric variables. We found
      strong evidence that Westerners and Easterners constitute two distinct and
      independent microevolutionary universes when cranial morphology is assessed. The
      existence of a third universe, Northwest, cannot be completely ruled out, but
      needs further investigation. We also discovered that Westerners and Easterners
      present similar degrees of internal variation, contrary to the findings of
      geneticists and molecular biologists. Palaeoamericans seem to be more similar to
      Easterners than to Westerners and North-Westerners. Our results suggest that this
      East-West cranial differentiation is more probably the result of differential
      rates of genetic drift and gene flow acting on each side of the Cordillera.
      However, different intensities of gene flow between Palaeoamericans and
      Amerindians in the highlands and in the lowlands cannot be completely dismissed
      as a possible explanation for the differentiation found.

PMID- 16574118
TI  - Sex- and age-related variations of the somatotype in a Chuvasha population.
AB  - The aim of this large, cross-sectional study was to describe the age- and sex
      related variations of the somatotype, employing Heath and Carter's method, in a
      Chuvasha population residing in a rural region in central Russia. The
      investigated sample included 802 males aged 18-89 years (mean 46.9) and 738
      females aged 18-90 years (mean 48.6). We evaluated the age and sex differences by
      one-way ANOVA with somatotype components as dependent variables and sex or age
      groups as grouping variables. Sex differences of somatotypes appear to be the
      strongest for endomorphy, with generally higher values in women. Endomorphy in
      males remained virtually unchanged after 30 years of age, but endomorphy in
      females kept increasing up to the 6th decade, and then subsequently decreased.
      Virtually no differences were noted in mesomorphy and a very small difference in
      ectomorphy between males and females aged 18-30 years. A reduction of sexual
      dimorphism in all somatotype components after age 70 was also observed. The
      largest difference of all somatotype components appeared between age groups 18-30
      and 31-40 years. Thereafter, somatotypes remained practically unchanged.
      Mesomorphy continued to increase until the 5th decade in both sexes, while in
      females, endomorphy continuously increased until their 6th decade. In the 7th and
      8th decades, a decrease in mean values was observed. Mesomorphy and ectomorphy
      showed opposite age-related trends. Results of our study clearly suggest that in
      physique investigations, the somatotypes need to be studied in each sex
      separately, and in studies of young people, they need also to be adjusted to age.

PMID- 16574119
TI  - Impact of social environment on female chimpanzee reproductive cycles.
AB  - The socio-sexual environment of a female is known to affect ovarian function.
      Increased male contact can enhance menstrual cycle regularity. Conversely, social
      deprivation constitutes a form of stress that often alters cyclicity and the
      secretion of reproductive hormones. The present study was carried out on captive
      female chimpanzees to examine possible interactions among housing conditions,
      menstrual cycle length, morphological changes in secondary sexual character
      expression and endocrine release patterns related to follicular and luteal
      function. Animals were housed over a period of 2 years either with a male
      conspecific or singly. Blood samples were collected over three cycles, and
      anogenital swelling changes registered to define menstrual cycle phases. Fecal
      sampling techniques were used to monitor cortisol as a measure of stress-load.
      Male presence seemed to affect female cyclicity. Females housed with a male had
      shorter and more regular cycles than singly housed females. Prolactin,
      gonadotropins and estradiol levels were generally higher in paired females during
      specific cycle phases. Group variation was not always significant. No differences
      were found in progesterone. Sexually cohabited females tended to have lower fecal
      cortisol metabolites immediately before and after maximum tumescence. We suggest
      that the close behavioral, physical and olfactory contact with a male conspecific
      can act as a sort of zeitgeber to modulate ovarian function by stabilizing the
      female cycle and, perhaps, enhancing folliculogenesis and ovulation.

PMID- 16574120
TI  - Management of nonunion with distraction osteogenesis.
AB  - Nonunions of long bone fractures represent a clinical entity that is commonly
      perpetuated by a high velocity injury. There are both bony and soft tissue
      factors responsible for the nonunion. This paper is focused on the reported
      clinical and radiographic outcomes whenever treatment protocols pertaining to
      distraction osteogenesis are implemented.

PMID- 16574121
TI  - What leads to unfavourable Cybex test results for quadriceps power after modified
      tension band osteosynthesis of patellar fractures?
AB  - This study recruited 20 patients who had undergone modified tension band wiring
      for patellar fracture, with a mean follow up of 30 months. Subjects were grouped
      according to results of Cybex isokinetic testing at 60 degrees /s angular
      velocity. Subjects with <30% deficit as compared with the contralateral knee
      constituted group I, and those with >30% similar deficit formed group II. Plain
      radiography and HSS scoring were also performed. According to patient
      satisfaction, HSS scoring and Cybex testing, results were good in 80%, 90% and
      55% of cases, respectively. Statistical analysis revealed that there were no
      significant differences between the two groups in terms of age, gender, duration
      of follow up, fracture type (two-part or comminuted), dominancy, time interval
      between trauma and surgery, or duration of immobilisation. The number of patients
      with >1 mm articular incongruity postoperatively was significantly higher in
      group II, which also had significantly higher incidences of >1 cm thigh atrophy
      and pain and thus increased deficits. We suggest that articular incongruity
      should be limited strictly to 1mm in surgery for patellar fractures.

PMID- 16574122
TI  - Management of cervical stab wounds in low volume trauma centres: systematic
      physical examination and low threshold for adjunctive studies, or surgical
      exploration.
AB  - INTRODUCTION: In Nordic countries penetrating neck injuries (PNIs) are infrequent
      and management has traditionally been guided by surgeons' preferences. Some form
      of selective non-operative approach is currently practised in most urban trauma
      centres. OBJECTIVE: To examine demographic features and treatment outcome of non
      ballistic penetrating neck injuries in southern Finland and provide management
      guidelines for centres with low volume of penetrating neck trauma. MATERIALS AND
      METHODS: Retrospective analysis of 85 platysma penetrating neck injuries in two
      southern Finland hospitals (Helsinki University Central Hospital, HUCH and
      Tampere University Hospital, TaUH) was carried out using the ICD-10 based
      hospital databases to identify PNI-patients. RESULTS: The incidence of admitted
      patients with penetrating neck injuries was 1.3/100000/year. Fifty-two (61%)
      injuries were caused by random acts of violence, 28 (38%) were self-inflicted and
      5 (6%) were accidents. Of all 85 patients, 52 (61%) underwent operative
      exploration with a negative exploration rate of 65%. Hard signs for vascular or
      aerodigestive trauma were present in 23 (27%) patients and all of these were
      operated with a negative exploration rate of 30%. Two patients had no hard signs
      on physical examination but were operatively explored and significant injuries
      were found in both patients. The hospital mortality rate was 0% and the overall
      complication rate for operated patients was 7.7%. CONCLUSIONS: Trauma centres
      managing PNIs infrequently should have an individually tailored management
      protocol for penetrating neck injury patients. If mandatory exploration is not
      practised, a systematic physical examination should be the mainstay of diagnostic
      work up but the threshold for adjunctive studies should be low. Although not
      evident by the current data, protocol-based management could be useful in
      decreasing treatment variation and enhancing residency training.

PMID- 16574123
TI  - Developing a Research base for Intravenous Peripheral cannula re-sites (DRIP
      trial). A randomised controlled trial of hospital in-patients.
AB  - BACKGROUND: There is currently no high grade evidence on which to base decisions
      about the frequency of intravenous cannula re-sites. OBJECTIVE: To assess the
      safety of changing peripheral venous cannulas when clinically indicated. DESIGN:
      Randomised controlled trial. SETTING: A tertiary referral hospital in Brisbane,
      Australia. PARTICIPANTS: Two hundred and six hospitalised patients from surgical,
      medical and orthopaedic wards. INTERVENTIONS: Peripheral intravenous cannulas
      were re-sited only when complications occurred (intervention group) or every 3
      days (control group). MAIN OUTCOME MEASURES: The primary endpoint was any
      unplanned cannula removal, the secondary outcome was cost. RESULTS: Forty six
      patients had unplanned removals in the intervention group compared with 41 in the
      control group [relative risk 1.12, 95% confidence interval 0.81-1.55 (p=0.286)],
      a non-significant difference. Total duration of peripheral cannulation was
      similar in both groups (mean 123.3h in the intervention group and 125.9h in the
      control group: P=0.82) but significantly more re-sites occurred in the control
      group (167 in intervention group, 202 in the control group: p=0.022). Cost of
      cannula replacements in the intervention group was AUD$3,183.62 and in the
      control group AUD$3,837.56 (p=0.006). CONCLUSION: Re-siting peripheral venous
      cannulas when clinically indicated compared with changing them routinely every 3
      days does not lead to more complications and reduces costs.

PMID- 16574124
TI  - Dehydroepiandrosterone inhibits the TNF-alpha-induced inflammatory response in
      human umbilical vein endothelial cells.
AB  - Dehydroepiandrosterone (DHEA) has a protective role against atherosclerosis. We
      determined the effect of pharmacological doses of DHEA upon the adhesion of
      monocytic U937 cells to human umbilical vein endothelial cells (HUVEC), as well
      as the expression of adhesion and chemoattractant molecules, the translocation of
      NF-kappaB, the degradation of IkappaB-alpha and the production of reactive oxygen
      species (ROS) in HUVEC. Adhesion of U937 cells to DHEA-treated HUVEC was
      evaluated by co-culture experiments using [(3)H]-thymidine-labeled U937 cells.
      The expression of adhesion and chemoattractant molecules was evaluated by flow
      cytometry and RT-PCR, respectively; NF-kappaB translocation was determined by
      Electrophoretic Mobility Shift Assay (EMSA) and IkappaB-alpha degradation by
      Western blot. ROS production was determined by the reduction of fluorescent
      DCFDA. TNF-alpha was used to induce inflammatory responses in HUVEC. One hundred
      micromolar of DHEA-treatment inhibited the TNF-alpha-induced expression of ICAM
      1, E-selectin, ROS production and U937 cells adhesion to HUVEC, and interfered
      with NF-kappaB translocation and IkappaB-alpha degradation. DHEA at the above
      mention concentration also inhibited the mRNA expression of MCP-1 and IL-8 in
      basal conditions but not in TNF-alpha-stimulated conditions. Our results suggest
      that DHEA inhibits the expression of molecules involved in the inflammatory
      process, therefore it could be used as an alternative in the treatment of chronic
      inflammatory diseases such as atherosclerosis.

PMID- 16574125
TI  - Clinical significance of a high ankle-brachial index: insights from the
      Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND: The clinical significance of a high ankle-brachial index (ABI),
      defined by the associated risk factor burden and ischemic risk, is largely
      unknown. METHODS: Using data from the Atherosclerosis Risk in Communities Study,
      we categorized 14,777 participants into normal (ABI between 0.9 and 1.3) and high
      ABI groups (ABI>1.3, >1.4, and >1.5) and compared the risk factor profile and CVD
      event rates of the normal ABI group to each high ABI group. RESULTS: The
      prevalence of high ABI was 5.5% for ABI>1.3, 1.2% for ABI>1.4, and 0.37% for
      ABI>1.5. Compared with participants with a normal ABI, those with ABI>1.3 had a
      lower prevalence of hypertension and current smoking. The ABI>1.3 group had a
      greater mean body mass index, but was characterized by fewer pack years of
      smoking and lower systolic and diastolic blood pressures than the normal ABI
      group. The prevalence of diabetes, left ventricular hypertrophy, claudication,
      and coronary heart disease and mean values of fibrinogen, factor VIII activity,
      von Willebrand factor, lipoprotein (a), and carotid and popliteal intimal-medial
      thickness were similar between the two ABI groups. The risk factor profiles of
      the ABI>1.4 and >1.5 groups were also not statistically significantly different
      from that of the normal ABI group. Over a mean follow-up time of 12.2 years, the
      age, sex, and race-adjusted CVD event rates per 1000 person years were 8.1 in the
      normal ABI group, 7.6 in the ABI>1.3 group, 7.6 in the ABI>1.4 group, and 7.4 in
      the ABI>1.5 group. The CVD event rates of the high ABI groups were similar to
      that of the normal ABI group. CONCLUSION: Individuals with a high ABI are not
      characterized by a more adverse atherosclerosis risk factor profile and do not
      suffer greater CVD event rates than those with a normal ABI.

PMID- 16574126
TI  - The FORT test--a novel oxidative stress marker or a well-known measure of
      ceruloplasmin oxidase activity?

PMID- 16574127
TI  - A finite shell element for heart mitral valve leaflet mechanics, with large
      deformations and 3D constitutive material model.
AB  - This paper presents a shell finite element formulation appropriate for simulating
      the heart valve leaflet mechanics, including three-dimensional (3D) stress and
      strain effects. A 4-node mixed-interpolation shell is formulated in convected
      coordinates. This shell model is made capable of handling arbitrary 3D material
      models by use of an algorithm that satisfies the shell stress assumption at every
      element integration point. A method for tracking the fiber direction is
      incorporated. The resulting shell element operates under the same conditions as a
      standard 4-node shell element with 5 degrees of freedom per node, but extends the
      modeling capabilities to handle large-deformation and anisotropic behavior.

PMID- 16574128
TI  - "Flow-induced hardening of endothelial nucleus..." by Deguchi et al.

PMID- 16574129
TI  - Determination of gamma- and alpha-tocopherols in human milk by a direct high
      performance liquid chromatographic method with UV-vis detection and comparison
      with evaporative light scattering detection.
AB  - A rapid direct method (Method I) for measuring gamma- and alpha-tocopherols in
      human milk was developed and validated using reversed-phase high-performance
      liquid chromatography with ultraviolet/visible (UV-vis) detection. Human milk,
      with an internal standard (alpha-tocopherol acetate) added, was diluted in
      hexane. The chromatographic system consisted of a short column (50 mm x 2.1mm
      I.D., 3 microm particle size) that allowed the separation of the gamma- and alpha
      tocopherols in less than 6 min. The new direct method (Method I) was compared
      with other methods. Method II (saponification with ultraviolet/visible detection)
      determined 24% and 22% less gamma- and alpha-tocopherols, respectively. Method
      III (saponification with evaporative light scattering detection) gave the same
      values for alpha-tocopherol content as Method II. However, the amount of sample
      used in the application of Method III was higher than that used in Method II.
      Furthermore, Method I uses smaller amounts of solvents, and it is simpler and
      faster than Methods II or III. Only a small volume of sample is needed, which is
      an additional advantage for biological assays.

PMID- 16574130
TI  - Simultaneous determination of endocrine-disrupting phenols and steroid estrogens
      in sediment by gas chromatography-mass spectrometry.
AB  - A simple and effective method has been developed to simultaneously determine
      endocrine-disrupting phenolic xenoestrogens and steroid estrogens in sediment by
      using ultra-sonicated extraction in combination with silica gel fractionation,
      derivatization with pentafluropropionic anhydride, and gas chromatography-mass
      spectrometry (GC-MS) in selected ion monitoring mode (SIM). Satisfactory
      recoveries have been obtained for phenolic xenoestrogens and steroid estrogens.
      The method enables the determination of targets at concentrations of lower
      nanogram-per-gram in sediments. The method has been successfully applied to the
      sediments collected from Pearl River Estuary (PRE), South China Sea, China.
      Nonylphenol and bisphenol-A (BPA) were detected in the range from 204.2 to 664.5
      ng/g and 0.6 to 4.0 ng/g, respectively. None of the estrogens were found in the
      sediment samples.

PMID- 16574131
TI  - Adsorption behavior of hexafluorophosphate on selected bonded phases.
AB  - The adsorption behavior of ammonium hexafluorophosphate was studied on four HPLC
      columns packed with adsorbents of different ability for dispersive interactions
      using frontal chromatography with LC/MS detection in negative ESI mode.
      Hexafluorophosphate (PF(6)(-)) adsorption isotherms were measured from
      acetonitrile/water and methanol/water mixtures. Increased PF(6)(-) adsorption
      with increased acetonitrile content was found between 0 and 15% of acetonitrile
      in the eluent. Further increase of the acetonitrile concentration leads to an
      exponential decrease of PF(6)(-) adsorption. Methanol, on the other hand, causes
      a steady decrease of PF(6)(-) adsorption with increased organic concentration in
      the mobile phase.

PMID- 16574132
TI  - Quantitation of seven polyoxypregnane glycosides in Marsdenia tenacissima using
      reversed-phase high-performance liquid chromatography-evaporative light
      scattering detection.
AB  - A high-performance liquid chromatography coupled with an evaporative light
      scattering detector (HPLC-ELSD) has been developed for the simultaneous
      determination of seven polyoxypregnane glycosides, tenacissosides A, B, G, H, I
      and marsdenosides C, G, in the stem of Marsdenia tenacissima, a Chinese herbal
      medicine. With a C18 analytical column, the analytes were separated efficiently
      using methanol-water as the mobile phase in a gradient program. The method limits
      of detection ranged from ca. 0.3 microg for marsdenoside C to ca. 0.5 microg for
      marsdenoside G and the method limits of quantitation from 1.0 microg for
      marsdenoside C to 1.7 microg for marsdenoside G, respectively. The intra- and
      inter-day precisions of the method were evaluated and all were less than 4%. All
      the recoveries for the spiked analytes exceeded 90%. This method was successfully
      used to analyze 19 samples of the stem of M. tenacissima.

PMID- 16574133
TI  - Simultaneous extraction and determination of anionic surfactants in waters and
      sediments.
AB  - A new method has been developed for the simultaneous determination of the most
      frequently used anionic surfactants - linear alkylbenzene sulfonates (LAS), alkyl
      ethoxysulfates (AES) and alkyl sulfates (AS) - in aqueous and sediment samples.
      Preconcentration and purification of water samples are carried out by means of
      solid-phase extraction (SPE). The efficiency of two different extraction methods
      for the analysis of sediments - Soxhlet extraction and pressurized liquid
      extraction (PLE) - has been compared. Identification and quantification of the
      target compounds is performed using a liquid chromatography - mass spectrometry
      (LC-MS) system equipped with an electrospray interface (ESI) in negative ion
      mode. Homologue recoveries are 85-123% for SPE, 94-112% for Soxhlet extraction
      and 81-125% for PLE in the case of LAS, and 60-94% for SPE, 61-109% for Soxhlet
      extraction and 55-99% for PLE in the case of AES, whereas the limits of detection
      are 0.1-0.5 ngml(-1) in water and 1-5 ngg(-1) in sediment. This method has been
      applied to the determination of anionic surfactants in the Guadalete estuary (SW
      Spain), and LAS concentration levels from 538 to 1014 ngg(-1) in sediments and
      from 25.1 to 64.4 ngml(-1) in waters have been found. AES values from 168 to 536
      ngg(-1) in sediments and from 4.5 to 11.9 ngml(-1) in waters are reported for the
      first time in European rivers.

PMID- 16574134
TI  - Analysis of human serum by liquid chromatography-mass spectrometry: improved
      sample preparation and data analysis.
AB  - Discovery of biomarkers is a fast developing field in proteomics research. Liquid
      chromatography coupled on line to mass spectrometry (LC-MS) has become a powerful
      method for the sensitive detection, quantification and identification of proteins
      and peptides in biological fluids like serum. However, the presence of highly
      abundant proteins often masks those of lower abundance and thus generally
      prevents their detection and identification in proteomics studies. To perform
      future comparative analyses of samples from a serum bank of cervical cancer
      patients in a longitudinal and cross-sectional manner, methodology based on the
      depletion of high-abundance proteins followed by tryptic digestion and LC-MS has
      been developed. Two sample preparation methods were tested in terms of their
      efficiency to deplete high-abundance serum proteins and how they affect the
      repeatability of the LC-MS data sets. The first method comprised depletion of
      human serum albumin (HSA) on a dye ligand chromatographic and immunoglobulin G
      (IgG) on an immobilized Protein A support followed by tryptic digestion,
      fractionation by cation-exchange chromatography, trapping on a C18 column and
      reversed-phase LC-MS. The second method included depletion of the six most
      abundant serum proteins based on multiple immunoaffinity chromatography followed
      by tryptic digestion, trapping on a C18 column and reversed-phase LC-MS.
      Repeatability of the overall procedures was evaluated in terms of retention time
      and peak area for a selected number of endogenous peptides showing that the
      second method, besides being less time consuming, gave more repeatable results
      (retention time: <0.1% RSD; peak area: <30% RSD). Application of an LC-MS
      component detection algorithm followed by principal component analysis (PCA)
      enabled discrimination of serum samples that were spiked with horse heart
      cytochrome C from non-spiked serum and the detection of a concentration trend,
      which correlated to the amount of spiked horse heart cytochrome C to a level of 5
      pmol cytochrome C in 2 microl original serum.

PMID- 16574135
TI  - Determination of organic compounds in water using dispersive liquid-liquid
      microextraction.
AB  - A new microextraction technique termed dispersive liquid-liquid microextraction
      (DLLME) was developed. DLLME is a very simple and rapid method for extraction and
      preconcentration of organic compounds from water samples. In this method, the
      appropriate mixture of extraction solvent (8.0 microL C2Cl4) and disperser
      solvent (1.00 mL acetone) are injected into the aqueous sample (5.00 mL) by
      syringe, rapidly. Therefore, cloudy solution is formed. In fact, it is consisted
      of fine particles of extraction solvent which is dispersed entirely into aqueous
      phase. After centrifuging, the fine particles of extraction solvent are
      sedimented in the bottom of the conical test tube (5.0 +/- 0.2 microL). The
      performance of DLLME is illustrated with the determination of polycyclic aromatic
      hydrocarbons (PAHs) in water samples by using gas chromatography-flame ionization
      detection (GC-FID). Some important parameters, such as kind of extraction and
      disperser solvent and volume of them, and extraction time were investigated.
      Under the optimum conditions the enrichment factor ranged from 603 to 1113 and
      the recovery ranged from 60.3 to 111.3%. The linear range was 0.02-200 microg/L
      (four orders of magnitude) and limit of detection was 0.007-0.030 microg/L for
      most of analytes. The relative standard deviations (RSDs) for 2 microg/L of PAHs
      in water by using internal standard were in the range 1.4-10.2% (n = 5). The
      recoveries of PAHs from surface water at spiking level of 5.0 microg/L were 82.0
      111.0%. The ability of DLLME technique in the extraction of other organic
      compounds such as organochlorine pesticides, organophosphorus pesticides and
      substituted benzene compounds (benzene, toluene, ethyl benzene, and xylenes) from
      water samples were studied. The advantages of DLLME method are simplicity of
      operation, rapidity, low cost, high recovery, and enrichment factor.

PMID- 16574136
TI  - Trace analysis of tiamulin in honey by liquid chromatography-diode array
      electrospray ionization mass spectrometry detection.
AB  - A liquid chromatography with diode array or electrospray ionisation mass
      spectrometry detection (LC-DAD-ESI-MS) method for the determination of tiamulin
      residues in honey is presented. The procedure employs a solid-phase extraction
      (SPE) on polymeric cartridges for the isolation of tiamulin from honey samples
      diluted in aqueous solution of tartaric acid. Chromatographic separation of the
      tiamulin is performed, in isocratic mode, on a C18 column using methanol and
      ammonium carbonate 0.1% in water, in proportion (30:70, v/v). Average analyte
      recoveries were from 88 to 106% in replica sets of fortified honey samples. The
      LC-ESI-MS method detection limits differ from 0.5 microg kg(-1) for clear honeys
      to 1.2 microg kg(-1) for dark honeys. The developed method has been applied to
      the analysis of tiamulin residues in multifloral honey samples collected from
      veterinary treated beehives.

PMID- 16574137
TI  - Determination of polycyclic aromatic sulfur heterocycles in diesel particulate
      matter and diesel fuel by gas chromatography with atomic emission detection.
AB  - The sulfur content of diesel fuel is of environmental concern because sulfur can
      facilitate the formation of diesel particulate matter (DPM) and sulfur dioxide
      (SO2) in the exhaust can poison catalytic converters. The US Environmental
      Protection Agency (EPA) has established more stringent regulations to reduce the
      sulfur content of diesel fuels in the near future. In this study, various types
      of organosulfur compounds in DPM extracts and the corresponding fuels have been
      determined by gas chromatography with atomic emission detection. The diesel fuels
      used have sulfur contents of 2284 and 433 ppm, respectively, and are labeled as
      high-sulfur and low-sulfur diesel fuels. The compounds identified are mainly
      polycyclic aromatic sulfur heterocycles (PASHs). In the fuels tested,
      trimethylbenzothiophenes (TMBTs), dibenzothiophenes (DBTs), and 4
      methyldibenzothiophene (4-MDBT) were the most abundant sulfur compounds, while
      larger PASH compounds were more abundant in DPM extracts. The high-sulfur diesel
      fuel contained a larger proportion of PASHs with one or two rings (lighter
      PASHs). In DPM, the concentrations of total organic sulfur and individual PASHs
      are higher for the high-sulfur diesel fuel, and the relative percentage of one or
      two-ring PASHs is higher as well. The influence of engine load on the DPM
      composition was also examined. With increasing load, the PASH concentration in
      DPM decreased for lighter PASHs, increased for heavier PASHs, and had a bell
      shaped distribution for PASHs in between.

PMID- 16574138
TI  - Selective serotonin reuptake inhibitors in sewage influents and effluents from
      Tromso, Norway.
AB  - An analytical method for quantification of the selective serotonin reuptake
      inhibitors (SSRIs) citalopram, sertraline, paroxetine, fluoxetine and fluvoxamine
      in sewage influents and effluents from selected sewage treatment plants (STPs)
      has been developed and validated. This quantification method is based on solid
      phase extraction of 2.5L samples, followed by liquid-liquid extraction for
      further sample clean up in order to minimize matrix effects during subsequent
      quantification. The samples were analysed on a high performance liquid
      chromatograph coupled to a triple quadrupole mass spectrometric detector using
      0.1% ammonia in acetonitrile/water as mobile phase, with positive electrospray
      ionisation and multiple reaction monitoring for detection and quantification. 1
      [3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-pyrrolidine (N
      7084) was used as internal standard for quantification. The recovery rates of the
      SSRIs ranged between 54 and 84%, and the method limit of quantification (MLQ) was
      between 120 and 290 pg/L for the target compounds. Samples were collected in July
      2005 from three different STPs and a pump station in Tromso, Northern Norway. Two
      of the STPs serve the University hospital and its psychiatric department,
      respectively, in addition to domestic sewage. SSRIs were detected in all samples
      collected. The concentrations varied greatly from below the MLQ to several
      hundreds ng/L. Concentrations in influents were higher compared to filtered
      effluents, indicating that SSRIs adsorb to particulate matter, are degraded by
      microorganisms, or degraded in other ways during the filtration process. However,
      more samples should be analysed before general conclusions can be drawn.

PMID- 16574139
TI  - Analyte-stationary phase interactions in ion-exclusion chromatography.
AB  - The currently accepted analyte-stationary phase interactions occurring in ion
      exclusion chromatography are re-examined. In particular, the requirement for the
      existence of a Donnan membrane separating the flowing, interstitial eluent from
      the static, occluded, liquid acting as the stationary phase is scrutinized,
      together with the role of hydrophobic adsorption effects in the retention of
      aromatic analytes. Plots showing the interconversion of the column between the
      analyte and eluent forms are used to highlight some shortcomings of the currently
      accepted mechanism for ion-exclusion chromatography. An alternative retention
      mechanism for ion-exclusion chromatography is proposed, based on the presence of
      a potential well at the surface of the fully functionalized styrene
      divinylbenzene co-polymer stationary phase. Analytes diffuse into the potential
      well under the effects of concentration gradients, and undergo repulsion effects
      from the fixed charges inside the pores. The net contributions of these two
      opposing processes determine the degree to which an analyte is retained on the
      stationary phase. Negligible hydrophobic adsorption of the analyte onto the
      polymeric resin supporting the stationary phase is considered to occur.

PMID- 16574140
TI  - Morphology of hybrid polystyrene-block-poly(ethylene oxide) micelles: analytical
      ultracentrifugation and SANS studies.
AB  - Morphology and structure of aqueous block copolymer solutions based on
      polystyrene-block-poly(ethylene oxide) (PS-b-PEO) of two different compositions,
      a cationic surfactant, cetyl pyridinium chloride (CPC), and either platinic acid
      (H2PtCl6.6H2O) or Pt nanoparticles were studied using a combination of analytical
      ultracentrifugation (AUC), transmission electron microscopy (TEM), and small
      angle neutron scattering (SANS). These studies combining methods contributing
      supplemental and analogous structural information allowed us to comprehensively
      characterize the complex hybrid systems and to discover an isotope effect when
      H2O was replaced with D2O. In particular, TEM shows formation of both micelles
      and larger aggregates after incorporation of platinic acid, yet the amount of
      aggregates depends on the H2PtCl6.6H2O concentration. AUC reveals the presence of
      micelles and micellar clusters in the PS-b-PEO block copolymers solution and even
      larger (supermicellar) aggregates in hybrids (with CPC). Conversely, SANS applied
      to D2O solutions of the similar species indicates that micelles are spherical and
      no other micellar species are found in block copolymer solutions. To reconcile
      the SANS and AUC data, we carried out AUC examination of the corresponding D2O
      block copolymer solutions. These measurements demonstrate a pronounced isotope
      effect on micelle aggregation and micelle size, i.e., no micelle aggregation in
      D2O solutions, revealing good agreement of AUC and SANS data.

PMID- 16574141
TI  - Professionalism in long-term care settings.
AB  - Speech-language pathologists who serve elders in a variety of long-term care
      settings have a variety of professional skills and responsibilities. Fundamental
      to quality service is knowledge of aging and communication changes and disorders
      associated with this process, institutional alternatives, and the changing nature
      of today's elders in long-term care. Excellence in service also involves meeting
      third party payers' requirements, teamwork, and advocacy. In addition,
      professionalism is demonstrated through maintaining privacy, ethical practice,
      staff and family in-service and counseling, and self-care. Innovative programming
      also involves developing new outcome measures and environmental engineering that
      enhances the communication skills and opportunities of elders in long-term care
      settings. LEARNING OUTCOMES: As a result of this activity, the participant will:
      (1) describe the changing nature of long-term care settings and residents, (2)
      understand the broad and complex professional skills that contribute to
      excellence in practice in this setting.

PMID- 16574142
TI  - Effect of different hapten-carrier conjugation ratios and molecular orientations
      on antibody affinity against a peptide antigen.
AB  - Hapten-carrier conjugate immunization is an important tool in the generation of
      hapten-specific antibodies for analytical purposes and in the uncovering of basic
      vaccine-immunological mechanisms. The affinity of antibodies is known to play an
      important role for the resulting sensitivity of antibody-based assay systems and
      in deciding whether a vaccine-induced antibody response will be protective. With
      ovalbumin as a carrier protein and a peptide (7.2 NY) representing a 19 amino
      acid sequence from the E. coli-derived Verotoxin 2e as a model hapten we
      investigated whether it was possible to influence the affinity and titre of
      antibodies raised against the hapten using different conjugation ratios and
      orientations. The peptide was coupled to ovalbumin in four conjugation ratios and
      two molecular orientations - terminal and central - and the conjugates were
      verified by mass spectrometry. Mice were immunised ten times at two-weeks
      intervals with low doses of the eight conjugates. Blood samples collected between
      each immunisation were analysed by ELISA for specific antibody titres and
      relative affinities. With both types of conjugations, the anti-peptide antibody
      titres increased in response to increasing conjugation ratios, but central
      conjugation resulted in markedly higher titres than terminal conjugation. The
      overall anti-peptide antibody affinities reached approximately similar levels
      with both orientations, whereas a reversed proportionality was observed between
      conjugation ratio and antibody affinity for terminal conjugation. Thus, it
      appears that the molar ratio of a peptide and its carrier may affect the
      resulting antibody affinities, and that a conjugation ratio between a terminally
      conjugated peptide and its carrier approaching one will result in relatively high
      antibody affinities. Furthermore, the molecular orientation of the coupled
      peptide has a major effect on the anti-peptide antibody titres induced.

PMID- 16574143
TI  - Nosema ceranae, a new microsporidian parasite in honeybees in Europe.
AB  - Twelve samples of adult honey bees from different regions of Spain from colonies
      with clear signs of population depletion, positive to microsporidian spores using
      light microscopy (1% of total positive samples analysed), were selected for
      molecular diagnosis. PCR specific primers for a region of the 16S rRNA gene of
      Microsporidia were developed and the PCR products were sequenced and compared to
      GenBank entries. The sequenced products of 11 out of the 12 samples were
      identical to the corresponding Nosema ceranae sequence. This is the first report
      of N. ceranae in colonies of Apis mellifera in Europe. The suggested link of the
      infections to clinical disease symptoms makes imperative a study of the virulence
      of N. ceranae in European races of honey bees.

PMID- 16574144
TI  - A rearranging ligand enables allosteric control of catalytic activity in copper
      containing nitrite reductase.
AB  - In Cu-containing nitrite reductase from Alcaligenes faecalis S-6 the axial
      methionine ligand of the type-1 site was replaced (M150G) to make the copper ion
      accessible to external ligands that might affect the enzyme's catalytic activity.
      The type-1 site optical spectrum of M150G (A(460)/A(600)=0.71) differs
      significantly from that of the native nitrite reductase (A(460)/A(600)=1.3). The
      midpoint potential of the type-1 site of nitrite reductase M150G (E(M)=312(+/
      5)mV versus hydrogen) is higher than that of the native enzyme (E(M)=213(+/
      5)mV). M150G has a lower catalytic activity (k(cat)=133(+/-6)s(-1)) than the wild
      type nitrite reductase (k(cat)=416(+/-10)s(-1)). The binding of external ligands
      to M150G restores spectral properties, midpoint potential (E(M)<225mV), and
      catalytic activity (k(cat)=374(+/-28)s(-1)). Also the M150H (A(460)/A(600)=7.7,
      E(M)=104(+/-5)mV, k(cat)=0.099(+/-0.006)s(-1)) and M150T (A(460)/A(600)=0.085,
      E(M)=340(+/-5)mV, k(cat)=126(+/-2)s(-1)) variants were characterized. Crystal
      structures show that the ligands act as allosteric effectors by displacing Met62,
      which moves to bind to the Cu in the position emptied by the M150G mutation. The
      reconstituted type-1 site has an otherwise unaltered geometry. The observation
      that removal of an endogenous ligand can introduce allosteric control in a redox
      enzyme suggests potential for structural and functional flexibility of copper
      containing redox sites.

PMID- 16574145
TI  - Local kinetic measures of macromolecular structure reveal partitioning among
      multiple parallel pathways from the earliest steps in the folding of a large RNA
      molecule.
AB  - At the heart of the RNA folding problem is the number, structures, and
      relationships among the intermediates that populate the folding pathways of most
      large RNA molecules. Unique insight into the structural dynamics of these
      intermediates can be gleaned from the time-dependent changes in local probes of
      macromolecular conformation (e.g. reports on individual nucleotide solvent
      accessibility offered by hydroxyl radical (()OH) footprinting). Local measures
      distributed around a macromolecule individually illuminate the ensemble of
      separate changes that constitute a folding reaction. Folding pathway
      reconstruction from a multitude of these individual measures is daunting due to
      the combinatorial explosion of possible kinetic models as the number of
      independent local measures increases. Fortunately, clustering of time progress
      curves sufficiently reduces the dimensionality of the data so as to make
      reconstruction computationally tractable. The most likely folding topology and
      intermediates can then be identified by exhaustively enumerating all possible
      kinetic models on a super-computer grid. The folding pathways and measures of the
      relative flux through them were determined for Mg(2+) and Na(+)-mediated folding
      of the Tetrahymena thermophila group I intron using this combined experimental
      and computational approach. The flux during Mg(2+)-mediated folding is divided
      among numerous parallel pathways. In contrast, the flux during the Na(+)-mediated
      reaction is predominantly restricted through three pathways, one of which is
      without detectable passage through intermediates. Under both conditions, the
      folding reaction is highly parallel with no single pathway accounting for more
      than 50% of the molecular flux. This suggests that RNA folding is non-sequential
      under a variety of different experimental conditions even at the earliest stages
      of folding. This study provides a template for the systematic analysis of the
      time-evolution of RNA structure from ensembles of local measures that will
      illuminate the chemical and physical characteristics of each step in the process.
      The applicability of this analysis approach to other macromolecules is discussed.

PMID- 16574146
TI  - The stability of transmembrane helix interactions measured in a biological
      membrane.
AB  - Despite some promising progress in the understanding of membrane protein folding
      and assembly, there is little experimental information regarding the
      thermodynamic stability of transmembrane helix interactions and even less on the
      stability of transmembrane helix-helix interactions in a biological membrane.
      Here we describe an approach that allows quantitative measurement of
      transmembrane helix interactions in a biological membrane, and calculation of
      changes in the interaction free energy resulting from substitution of single
      amino acids. Dimerization of several variants of the glycophorin A transmembrane
      domain are characterized and compared to the wild-type (wt) glycophorin A
      transmembrane helix dimerization. The calculated DeltaDeltaG(app) values are
      further compared with values found in the literature. In addition, we compare
      interactions between the wt glycophorin A transmembrane domain and helices in
      which critical glycine residues are replaced by alanine or serine, respectively.
      The data demonstrate that replacement of the glycine residues by serine is less
      destabilizing than replacement by alanine with a DeltaDeltaG(app) value of about
      0.4 kcal/mol. Our study comprises the first measurement of a transmembrane helix
      interaction in a biological membrane, and we are optimistic that it can be
      further developed and applied.

PMID- 16574147
TI  - Phosphorylation-dependent conformational switch in spin-labeled phospholamban
      bound to SERCA.
AB  - We have used chemical synthesis, functional reconstitution, and electron
      paramagnetic resonance (EPR) to probe the functional dynamics of phospholamban
      (PLB), which regulates the Ca-ATPase (SERCA) in cardiac sarcoplasmic reticulum.
      The transmembrane domain of PLB inhibits SERCA at low [Ca(2+)], but the
      cytoplasmic domain relieves this inhibition upon Ser16 phosphorylation. Monomeric
      PLB was synthesized with Ala11 replaced by the 2,2,6,6-tetramethylpiperidine-1
      oxyl-4-amino-4-carboxylic acid (TOAC) spin label, which reports peptide backbone
      dynamics directly. PLB was reconstituted into membranes in the presence or
      absence of SERCA. TOAC-PLB showed normal inhibitory function, which was reversed
      by phosphorylation at Ser16 or by micromolar [Ca(2+)]. EPR showed that the PLB
      cytoplasmic domain exhibits two resolved conformations, a tense T state that is
      ordered and a relaxed R state that is dynamically disordered and extended. PLB
      phosphorylation shifts this equilibrium toward the R state and makes it more
      dynamic (hyperextended). Phosphorylation strongly perturbs the dynamics of SERCA
      bound PLB without dissociating the complex, while micromolar [Ca(2+)] has no
      effect on PLB dynamics. A lipid anchor synthetically attached to the N terminus
      of PLB permits Ca-dependent SERCA inhibition but prevents the phosphorylation
      induced disordering and reversal of inhibition. We conclude that the relief of
      SERCA inhibition by PLB phosphorylation is due to an order-to-disorder transition
      in the cytoplasmic domain of PLB, which allows this domain to extend above the
      membrane surface and induce a structural change in the cytoplasmic domain of
      SERCA. This mechanism is distinct from the one that relieves PLB-dependent SERCA
      inhibition upon the addition of micromolar [Ca(2+)].

PMID- 16574148
TI  - Crystal structure of yeast peroxisomal multifunctional enzyme: structural basis
      for substrate specificity of (3R)-hydroxyacyl-CoA dehydrogenase units.
AB  - (3R)-hydroxyacyl-CoA dehydrogenase is part of multifunctional enzyme type 2 (MFE
      2) of peroxisomal fatty acid beta-oxidation. The MFE-2 protein from yeasts
      contains in the same polypeptide chain two dehydrogenases (A and B), which
      possess difference in substrate specificity. The crystal structure of Candida
      tropicalis (3R)-hydroxyacyl-CoA dehydrogenase AB heterodimer, consisting of
      dehydrogenase A and B, determined at the resolution of 2.2A, shows overall
      similarity with the prototypic counterpart from rat, but also important
      differences that explain the substrate specificity differences observed. Docking
      studies suggest that dehydrogenase A binds the hydrophobic fatty acyl chain of a
      medium-chain-length ((3R)-OH-C10) substrate as bent into the binding pocket,
      whereas the short-chain substrates are dislocated by two mechanisms: (i) a short
      chain-length 3-hydroxyacyl group ((3R)-OH-C4) does not reach the hydrophobic
      contacts needed for anchoring the substrate into the active site; and (ii) Leu44
      in the loop above the NAD(+) cofactor attracts short-chain-length substrates away
      from the active site. Dehydrogenase B, which can use a (3R)-OH-C4 substrate, has
      a more shallow binding pocket and the substrate is correctly placed for
      catalysis. Based on the current structure, and together with the structure of the
      2-enoyl-CoA hydratase 2 unit of yeast MFE-2 it becomes obvious that in yeast and
      mammalian MFE-2s, despite basically identical functional domains, the assembly of
      these domains into a mature, dimeric multifunctional enzyme is very different.

PMID- 16574149
TI  - Conservation of residues involved in sugar/H(+) symport by the sucrose permease
      of Escherichia coli relative to lactose permease.
AB  - Building a three-dimensional model of the sucrose permease of Escherichia coli
      (CscB) with the X-ray crystal structure lactose permease (LacY) as template
      reveals a similar overall fold for CscB. Moreover, despite only 28% sequence
      identity and a marked difference in substrate specificity, the structural
      organization of the residues involved in sugar-binding and H(+) translocation is
      conserved in CscB. Functional analyses of mutants in the homologous key residues
      provide strong evidence that they play a similar critical role in the mechanisms
      of CscB and LacY.

PMID- 16574150
TI  - Molecular structure of a novel membrane protease specific for a stomatin homolog
      from the hyperthermophilic archaeon Pyrococcus horikoshii.
AB  - Membrane-bound proteases are involved in various regulatory functions. Our
      previous study indicated that the N-terminal region of an open reading frame,
      PH1510 (residues 16-236, designated as 1510-N) from the hyperthermophilic
      archaeon Pyrococcus horikoshii, is a serine protease with a catalytic Ser-Lys
      dyad that specifically cleaves the C-terminal hydrophobic residues of a membrane
      protein, the stomatin-homolog PH1511. In humans, an absence of stomatin is
      associated with a form of hemolytic anemia known as hereditary stomatocytosis,
      but the function of stomatin is not fully understood. Here, we report the crystal
      structure of 1510-N in dimeric form. Each active site of 1510-N is rich in
      hydrophobic residues, which accounts for the substrate-specificity. The monomer
      of 1510-N shows structural similarity to one monomer of Escherichia coli ClpP, an
      ATP-dependent tetradecameric protease. But, their oligomeric forms are different.
      Major contributors to dimeric interaction in 1510-N are the alpha7 helix and
      beta9 strand, both of which are missing from ClpP. While the long handle region
      of ClpP contributes to the stacking of two heptameric rings, the corresponding L2
      loop of 1510-N is disordered because the region has little interaction with other
      residues of the same molecule. The catalytic Ser97 of 1510-N is in almost the
      same location as the catalytic Ser97 of E.coli ClpP, whereas another residue,
      Lys138, presumably forming the catalytic dyad, is located in the disordered L2
      region of 1510-N. These findings suggest that the binding of the substrate to the
      catalytic site of 1510-N induces conformational changes in a region that includes
      loop L2 so that Lys138 approaches the catalytic Ser97.

PMID- 16574151
TI  - Intra- versus intermolecular interactions in monellin: contribution of surface
      charges to protein assembly.
AB  - The relative significance of weak non-covalent interactions in biological context
      has been much debated. Here, we have addressed the contribution of Coulombic
      interactions to protein stability and assembly experimentally. The sweet protein
      monellin, a non-covalently linked heterodimeric protein, was chosen for this
      study because of its ability to spontaneously reconstitute from separated
      fragments. The reconstitution of monellin mutants containing large surface charge
      perturbations was compared to the thermostability of structurally equivalent
      single-chain monellin containing the same sets of mutations under varying salt
      concentrations. The affinity between monellin fragments is found to correlate
      with the thermostability of single chain monellin, indicating the involvement of
      the same underlying Coulombic interactions. This confirms that there are no
      principal differences in the interactions involved in folding and binding. Based
      on comparison with a previous mutational study involving hydrophobic core
      residues, the relative contribution of Coulombic interactions to stability and
      affinity is modest. However, the Coulombic perturbations only affect the
      association rates of reconstitution in contrast to perturbations involving
      hydrophobic residues, which affect primarily the dissociation rates. These
      results indicate that Coulombic interactions are likely to be of main importance
      for the association of protein assembly, relevant for functions of proteins.

PMID- 16574152
TI  - A novel processive mechanism for DNA synthesis revealed by structure, modeling
      and mutagenesis of the accessory subunit of human mitochondrial DNA polymerase.
AB  - Mitochondrial DNA polymerase (pol gamma) is the sole DNA polymerase responsible
      for replication and repair of animal mitochondrial DNA. Here, we address the
      molecular mechanism by which the human holoenzyme achieves high processivity in
      nucleotide polymerization. We have determined the crystal structure of human pol
      gamma-beta, the accessory subunit that binds with high affinity to the catalytic
      core, pol gamma-alpha, to stimulate its activity and enhance holoenzyme
      processivity. We find that human pol gamma-beta shares a high level of structural
      similarity to class IIa aminoacyl tRNA synthetases, and forms a dimer in the
      crystal. A human pol gamma/DNA complex model was developed using the structures
      of the pol gamma-beta dimer and the bacteriophage T7 DNA polymerase ternary
      complex, which suggests multiple regions of subunit interaction between pol gamma
      beta and the human catalytic core that allow it to encircle the newly synthesized
      double-stranded DNA, and thereby enhance DNA binding affinity and holoenzyme
      processivity. Biochemical properties of a novel set of human pol gamma-beta
      mutants are explained by and test the model, and elucidate the role of the
      accessory subunit as a novel type of processivity factor in stimulating pol gamma
      activity and in enhancing processivity.

PMID- 16574154
TI  - A role for replication repair in the genesis of templated mutations.
AB  - Replication repair mediates error-free bypass of DNA damage in a series of steps
      that include regression of the replication fork, primer-terminus switching to use
      the other daughter strand as an undamaged template, primer extension, primer
      switching back to its cognate template with the primer terminus now having
      bypassed the damage, and fork rearrangement to a normal configuration. By both
      genetic and biochemical criteria, bacteriophage T4 catalyzes replication repair
      with two alternative sets of proteins, one including the gp32 SSB and the gp41
      DNA helicase and the other including the UvsX recombinase. In each pathway,
      synthesis is conducted by the gp43 DNA polymerase. Here we show that defects in
      gp32, gp41 or UvsX that impair replication repair also increase mutation rates
      generally, but especially for templated mutations. Such templated mutations are
      associated with palindromic or direct repeats that are either perfect or
      imperfect. Models of templated mutagenesis require that the primer terminus
      switches to an ectopic template, but one that yields mutations instead of error
      free bypass. We suggest that the proteins that conduct replication repair
      normally direct a blocked primer strand specifically to the other daughter strand
      with considerable accuracy, but that strand switching becomes promiscuous when
      these proteins are mutationally impaired, thus promoting templated mutations.

PMID- 16574155
TI  - Dynamic imbalance in gait ataxia. Characteristics of plantar pressure
      measurements.
AB  - The present study was designed to evaluate the interaction between disequilibrium
      and irregular stepping components of ataxic gait. For this purpose, we compared
      the walking patterns of patients with cerebellar dominant multiple system atrophy
      (MSAc, n = 8), spinocerebellar ataxia type 6 (SCA6, n = 4) and 16q-linked
      autosomal dominant cortical cerebellar atrophy (16q-linked ADCA, n = 6), and 6
      normal subjects, by measuring toe and heel plantar pressures. In healthy
      subjects, the heel contacted the floor at step-in followed by an immediate shift
      of the center of pressure (COP) to the contacted leg. In ataxic gait, however,
      both the heel and toes simultaneously contacted the floor and the disappearance
      of the immediate shift of the COP was noted. These changes appeared to be
      nonspecific compensations for the instability. Examination of two parameters of
      ataxia-specific changes showed that prolongation of the double support period was
      associated with proportionate increase in the coefficients of variance of the
      plantar pressures and the step lengths on walking of patients with SCA6, but not
      those with MSAc and 16q-linked ADCA. Our results suggest that disequilibrium and
      irregularity are two separate and independent components of cerebellar ataxic
      gait.

PMID- 16574156
TI  - Mechanistic model of fuel selection in the muscle.
AB  - Fuel selection in human muscle is key to explaining insulin resistance. In
      obesity and type 2 diabetes mellitus, there is an increased content of lipid
      within and around muscle fibers. Changes in muscle fuel partitioning of lipid,
      between oxidation and storage of fat, contribute to the accumulation of
      intramuscular triglycerides and to the pathogenesis of both obesity and type 2
      diabetes mellitus. A mathematical model of the aggregated metabolism in skeletal
      muscle was developed and the effects of fuel selection for lean and obese
      individuals under fasting conditions, insulin-stimulated conditions, and
      oscillating insulin conditions were examined. Model results were complementary to
      prior observations that elevated lipid oxidation during insulin-stimulated
      conditions is correlated with insulin resistance. The model also adequately
      simulated metabolic inflexibility between fat and glucose oxidation in the obese
      individual. A novel sensitivity analysis indicated the strong interaction effects
      of parameters of glucose and lipid oxidation pathways on the variables of each
      pathway.

PMID- 16574157
TI  - Perturbation avalanches and criticality in gene regulatory networks.
AB  - Boolean networks are simplified models of gene regulatory networks. We derive an
      approximation of the size distribution of perturbation avalanches in Boolean
      networks based on known results in the theory of branching processes. We show
      numerically that the approximation works well for different kinds of Boolean
      networks. It has been suggested that gene regulatory networks may be dynamically
      critical. To study this, as an application of the presented theory we present a
      novel method for estimating an order parameter from microarray data. According to
      the available data and our method, we find that gene regulatory networks appear
      to be stable and reside near the phase transition between order and chaos.

PMID- 16574153
TI  - Sequence alignment and homology threading reveals prokaryotic and eukaryotic
      proteins similar to lactose permease.
AB  - Certain prokaryotic transport proteins similar to the lactose permease of
      Escherichia coli (LacY) have been identified by BLAST searches from available
      genomic databanks. These proteins exhibit conservation of amino acid residues
      that participate in sugar binding and H(+) translocation in LacY. Homology
      threading of prokaryotic transporters based on the X-ray structure of LacY (PDB
      ID: 1PV7) and sequence similarities reveals a common overall fold for sugar
      transporters belonging to the Major Facilitator Superfamily (MFS) and suggest new
      targets for study. Evolution-based searches for sequence similarities also
      identify eukaryotic proteins bearing striking resemblance to MFS sugar
      transporters. Like LacY, the eukaryotic proteins are predicted to have 12
      transmembrane domains (TMDs), and many of the irreplaceable residues for sugar
      binding and H(+) translocation in LacY appear to be largely conserved. The
      overall size of the eukaryotic homologs is about twice that of prokaryotic
      permeases with longer N and C termini and loops between TMDs III-IV and VI-VII.
      The human gene encoding protein FLJ20160 consists of six exons located on more
      than 60,000 bp of DNA sequences and requires splicing to produce mature mRNA.
      Cellular localization predictions suggest membrane insertion with possible
      proteolysis at the N terminus, and expression studies with the human protein
      FJL20160 demonstrate membrane insertion in both E.coli and Pichia pastoris.
      Widespread expression of the eukaryotic sugar transport candidates suggests an
      important role in cellular metabolism, particularly in brain and tumors. Homology
      is observed in the TMDs of both the eukaryotic and prokaryotic proteins that
      contain residues involved in sugar binding and H(+) translocation in LacY.

PMID- 16574158
TI  - Strain differences in the distribution of dopamine (DA-2 and DA-3) receptor sites
      in rat brain.
AB  - The dopamine (DA) pathway mediates numerous neuronal functions which are
      implicated in psychiatric disorders. Previously, our lab investigated the status
      of the dopamine transporter in the Wistar-Kyoto rat, a purported rodent model of
      depressive behavior, and reported significant alterations in transporter binding
      sites in several brain regions when compared to control rat strains. Given that
      DA-2 and DA-3 receptors belong to the same class of DA receptors, are co
      localized in the mesolimbic and nigrostriatal regions of the brain and function
      as autoreceptors, this study mapped the distribution of central DA-2 and DA-3
      receptors in Wistar-Kyoto and Wistar rats. The results indicated that while the
      binding of 125I-sulpride to DA-2 receptors was higher in the nucleus accumbens
      (shell) and ventral tegmental area, it was lower in the nucleus accumbens (core),
      caudate putamen and hypothalamus in Wistar-Kyoto compared to Wistar rats. In
      contrast, the binding of 125I-sulpride to DA-3 receptors was higher in the
      caudate putamen, nucleus accumbens (shell and core) and islands of Calleja in
      Wistar-Kyoto compared to Wistar rats. Given that DA-2 like receptors in the
      ventral tegmental area function as autoreceptors, it is possible that the greater
      inhibitory effects exerted by DA-2 and DA-3 receptors in Wistar-Kyoto rats may
      lead to a net deficit in DA levels in areas receiving projection from this cell
      body area.

PMID- 16574159
TI  - The effect of N-acetylcysteine in combination with vitamin C on the activity of
      ornithine decarboxylase of lung carcinoma cells--In vitro.
AB  - Ornithine decarboxylase (ODC) is a marker of lung cancer and is a key enzyme in
      the synthesis of polyamines, which are necessary for the promotion of the growth
      of malignant cells. This study assesses the dose-dependent effect of N
      acetylcysteine (NAC), a chemopreventive agent, in combination with vitamin C (VC)
      on the activity of ODC in lung carcinoma cell line, NCI-H82. The cells were
      subjected to supplementation of NAC and VC both individually and in combination
      at different dosages for 24 h as well as 48 h. The cells were incubated with
      radiolabeled L-ornithine (14C) after the supplementation of NAC and VC
      individually as well as in combination. A microprocedure was carried out to
      estimate the activity of ODC in cells after 24 and 48 h of incubation. The
      activity which was found to be elevated in control cells was decreased
      significantly on drug supplementation in dose-dependent fashion. The content of
      nucleic acids also exhibited similar result and [3H]-thymidine incorporation was
      also affected by the supplementation.

PMID- 16574160
TI  - Steroidogenic impairment due to reduced ovarian transcription of cytochrome P450
      side-chain-cleavage (P450scc) and steroidogenic acute regulatory protein (StAR)
      during experimental nephrotic syndrome.
AB  - The nephrotic syndrome is a renal disease characterized by proteinuria,
      hypoproteinemia, edema and hyperlipidemia. It has been reported that female
      nephrotic rats are characterized by loss of the oestrus cycle, follicle atresia,
      low gonadotropin and steroid concentrations; particularly, undetectable estradiol
      levels. Therefore, to determine the mechanisms involved in the ovarian
      steroidogenesis impairment, in this present study we evaluated the ovarian
      expression of the essential steroidogenesis components: cytochrome P450 side
      cholesterol chain cleavage enzyme (P450scc) and steroidogenic acute regulatory
      protein (StAR). The experiments were conducted in the rat experimental model of
      nephrosis induced by puromycin aminonucleoside (PAN) and in control groups. The
      evaluation of the expression of P450scc and StAR mRNA were performed during the
      acute phase of nephrosis as well as after the exogenous administration of 1 or 4
      doses of human chorionic gonadotrophin (hCG), or a daily dose of FSH or FSH+hCG
      for 10 days. In addition, serum hormone concentrations, intra-ovarian steroid
      content, and the reproductive capacity were determined. The results revealed a
      decreased expression of mRNA of P450scc enzyme and StAR during nephrosis, and
      eventhough they increased after gonadotropins treatment, they did not conduce to
      a normal cycling rat period or fertility recovery. This study demonstrates that
      the mechanism by which ovarian steroid biosynthesis is altered during acute
      nephrosis involves damage at the P450scc and StAR mRNA synthesis and processing.

PMID- 16574162
TI  - Beneficial effects of ApoA-I on LPS-induced acute lung injury and endotoxemia in
      mice.
AB  - High density lipoprotein (HDL) binds lipopolysaccharide (LPS) and neutralizes its
      toxicity. The aim of our study was to investigate the effects of Apolipoprotein
      (ApoA-I), the major apolipoprotein of HDL, on LPS-induced acute lung injury (ALI)
      and endotoxemia. BALB/c mice were challenged with LPS, followed by ApoA-I or
      saline administration for 24h. The mice were then sacrificed and
      histopathological analysis of the lung was performed. We found that ApoA-I could
      attenuate LPS-induced acute lung injury and inflammation. To investigate the
      mechanisms, we measured tumor necrosis factor alpha (TNF-alpha), interleukin
      1beta (IL-1beta) and interleukin-6 (IL-6) levels in the serum and bronchoalveolar
      lavage (BAL) fluid and found that ApoA-I could significantly inhibit LPS-induced
      increases in the IL-1beta and TNF-alpha levels in serum (P<0.05, respectively),
      as well as in the IL-1beta, TNF-alpha, and IL-6 levels in BAL fluid (P<0.01 and
      P<0.05, P<0.05, respectively). Moreover, we evaluated the effect of ApoA-I on the
      mortality of L-929 cells which were attacked by LPS-activated peritoneal
      macrophages. We found that ApoA-I could significantly inhibit the LPS-induced
      cell death in a dose-dependent fashion. Furthermore, we investigated in vivo the
      effects of ApoA-I on the mortality rate and survival time after LPS
      administration and found that ApoA-I significantly decreased the mortality
      (P<0.05) and increased the survival time (P<0.05). In summary, the results
      suggest that ApoA-I could effectively protect against LPS-induced endotoxemia and
      acute lung damage. The mechanism might be related to inhibition of inflammatory
      cytokine release from macrophages.

PMID- 16574161
TI  - Muscular cell proliferative and protective effects of N-acetylcysteine by
      modulating activity of extracellular signal-regulated protein kinase.
AB  - N-acetylcysteine (NAC), an antioxidant and a precursor of glutathione, is
      currently in clinical use for various pathological conditions. No data is
      available as to the relationship between NAC and muscular cell proliferation or
      muscular degenerative disease. In this study, we assessed the effect of NAC on
      growth of L6 myoblasts, a rat skeletal muscle cell line, under normal or
      bupivacaine-treated condition. Of interest, under normal growth conditions, NAC
      treatment concentration-dependently increased viability, cell number, and DNA
      incorporation of L6 cells. Remarkably, NAC treatment for 12 to 24 h led to
      increased phosphorylation of ERKs, a family of mitogen-activated protein kinase
      known to involve in cell proliferation, in L6 cells, and specific inhibition of
      ERKs by PD98059, a selective inhibitor of ERKs, greatly abolished the ability of
      NAC to increase the number of L6 cells. More importantly, pretreatment with NAC
      effectively blocked decrease in the number and ERKs phosphorylation in L6 cells
      induced by the exposure of bupivacaine, a local anesthetic with myotoxicity.
      These results collectively suggest that NAC has muscular cell proliferative and
      protective effects and the effects by NAC appear to be, in part, mediated via
      increase in ERKs activation.

PMID- 16574163
TI  - The impact of legislation on the usage and environmental concentrations of
      Irgarol 1051 in UK coastal waters.
AB  - In 2001, legislative measures were introduced in the UK to restrict usage of
      antifouling agents in small (<25 m) vessel paints to dichlofluanid, zinc
      pyrithione and zineb. This removed the previously popular booster biocides diuron
      and Irgarol 1051 from the market. To investigate the impact of this legislation,
      water samples were taken from locations where previous biocide levels were well
      documented. Results from analyses demonstrate a clear reduction in water
      concentrations of Irgarol 1051 (between 10% and 55% of that found during pre
      restriction studies), indicating that legislation appears to have been effective.
      Although other booster biocides were screened for (chlorothalonil, dichlofluanid
      and Sea-Nine 211), they were below the limits of detection (<1 ng/l) in all
      samples. A survey of chandlers and discussions with legislative authorities
      supports these results and concurs the removal of Irgarol 1051 based paints from
      the market using simple regulations at a manufacturer level with little
      regulation at a retailer level.

PMID- 16574164
TI  - Modulation of radiation response by inhibiting topoisomerase II catalytic
      activity.
AB  - Due to the essential role played by DNA topoisomerases (topos) in cell survival,
      the use of topoisomerase inhibitors as chemotherapeutic drugs in combination with
      radiation has become a common strategy for the treatment of cancer. Catalytic
      inhibitors of these enzymes would be promising to improve the effectiveness of
      radiation and therefore, it appears reasonable to incorporate them in combined
      modality trials. In this work, we have investigated the capacity of both ICRF-193
      and Aclarubicin (ACLA), two catalytic inhibitors of topoisomerase II (Topo II),
      to modulate radiation response in Chinese hamster V79 cell line and its
      radiosensitive mutant irs2. We also have explored potential mechanisms underlying
      these interactions. Experiments were performed in the presence and absence of
      either ICRF-193 or ACLA, and topo II activity was measured using an assay based
      upon decatenation of kinetoplast DNA (kDNA). For the combined experiments cells
      were incubated for 3 h in the presence of various inhibitor concentrations and
      irradiated 30 min prior to the end of treatments and cell survival was determined
      by clonogenic assay. DNA-damaging activity was measured by single-cell gel
      electrophoresis. Our results demonstrate that combinations of catalytic
      inhibitors of topo II and radiation produce an increase in cell killing induced
      by ionising radiation. The mechanism of radiation enhancement may involve a
      direct or indirect participation of topo II in the repair of radiation-induced
      DNA damage.

PMID- 16574165
TI  - Cisplatin-induced endoreduplication in CHO cells: DNA damage and inhibition of
      topoisomerase II.
AB  - It has been proposed that polyploid cells that arise during a variety of
      pathological conditions and as a result of exposure to genotoxicants, typically
      in the liver, become aneuploid through genetic instability. Aneuploidy
      contributes to, or even drives, tumour development. We have assessed the capacity
      of the drug cisplatin, one of the most commonly used compounds for the treatment
      of malignancies, to induce endoreduplication, a particular type of polyploidy, in
      cultured Chinese hamster AA8 cells. Taking into account that any interference
      with DNA topoisomerase II (topo II) function leads to endoreduplication, we have
      found that treatment of the cells with this platinum compound results in a dose
      dependent inhibition of the catalytic activity of the enzyme. These observations
      are discussed on the basis of a possible dual action of cisplatin leading to a
      combined negative effect on normal segregation of chromosomes. On the one hand,
      through the drug capacity to efficiently inhibiting the catalytic activity of
      topo II itself and, on the other hand, as a consequence of changes in DNA such as
      base modifications and cross-links that result from cisplatin treatment, likely
      leading to a lack of recognition/binding of DNA by the enzyme. These observations
      support a model in which the involvement of topo II in different pathways leading
      to induced endoreduplication has been proposed, and seem to bear significance as
      to the possible origin of the development of secondary tumours as a result of
      cisplatin treatment of primary malignancies.

PMID- 16574166
TI  - Immunofluorescent detection of 8-oxoguanine DNA lesions in liver cells from aging
      OXYS rats, a strain prone to overproduction of free radicals.
AB  - Production of free radicals in animals is accompanied with a number of pathologic
      conditions, some of which may be manifested through DNA damage. Studies of
      mechanisms of oxidative DNA damage by free radicals in vivo are hindered by the
      lack of good animal models with significant overgeneration of or increased
      sensitivity to free radicals. An inbred rat strain (OXYS) is characterized by
      inherited overgeneration of free radicals, lipid peroxidation, protein oxidation,
      DNA rearrangements, and pathological conditions paralleling several human
      degenerative diseases. We have used monoclonal antibodies against a common pre
      mutagenic base lesion 8-oxoguanine (8-oxoG) in combination with indirect
      immunofluorescence microscopy and image analysis to follow the relative age
      dependent amounts and distribution of 8-oxoG in liver cells from OXYS and Wistar
      rats. 8-OxoG increased with age in both strains of rats, with OXYS rats always
      displaying statistically significantly higher levels of oxidative DNA damage than
      Wistar rats. Statistical analysis indicates that 8-oxoG does not uniformly
      accumulate in all cells with advancing age or increasing free radical load, but
      rather concentrates in a minor fraction of cells with a high damage level.

PMID- 16574167
TI  - CyclinB2 and BIRC5 genes as surrogate biomarkers for neurite outgrowth in SH-SY5Y
      subclonal cells.
AB  - Neurite outgrowth plays a key role in neuronal development and regeneration, and
      is the hallmark assay for the effects of neurotrophic factors such as nerve
      growth factor (NGF). However, measuring neurite outgrowth is a slow and resource
      intensive process. We therefore wanted to identify surrogate biomarkers for
      neurite outgrowth activity by gene expression analysis in SH-O10 cells, a
      subclone of the human SH-SY5Y neuroblastoma cell line but with much higher NGF
      induced neurite outgrowth activity. Microarray analysis identified seven genes
      where mRNA levels were changed. NGF-induced decreases in levels of two genes,
      CyclinB2 and BIRC5, were confirmed by quantitative real-time RT-PCR. Levels of
      NGF-induced decreases in CyclinB2 and BIRC5 mRNA in several SH-SY5Y subclones
      with different neurite outgrowth responses correlated with their neurite
      outgrowth activities. Decreases in CyclinB2 and BIRC5 mRNA induced by FK506 or
      retinoic acid, both of which exert potentiation of NGF-induced neurite outgrowth
      effects but with different mechanisms, also correlated with their neurite
      outgrowth activities. In conclusion, decreasing levels of CyclinB2 and BIRC5 mRNA
      strongly correlate with neurite outgrowth activities in terms of NGF-related
      effect in SH-SY5Y subclonal cells, and have potential to become quantitative
      surrogate biomarkers for measuring NGF-related neurite outgrowth.

PMID- 16574168
TI  - Neural correlates of developmental differences in risk estimation and feedback
      processing.
AB  - The primary aim of this study was to compare the neural substrates of decision
      making in middle-aged children and adults. To this end, we collected fMRI data
      while 9-12-year-olds and 18-26-year-olds performed a simple gambling task. The
      task was designed to tap two important aspects of decision-making: risk
      estimation and feedback processing. We examined how orbitofrontal cortex (OFC),
      anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC)
      contributed to risk estimation, and how ventrolateral and medial prefrontal
      cortices (VLPFC and medial PFC) contributed to negative feedback processing in
      children and adults. Region of interest analyses revealed differences in brain
      activation between children and adults for ACC and lateral OFC. ACC was recruited
      more for high-risk than for low-risk trials, and this difference was larger for
      children than for adults. In contrast, children and adults did not differ in
      activation for OFC or DLPFC. These data suggest that children's decision-making
      under uncertainty is associated with a high degree of response conflict. Both age
      groups exhibited bilateral VLPFC (BA 47) and medial PFC/ACC (BA 6/ BA 32 (dorsal)
      and 24 (ventral)) activation associated with negative feedback processing.
      Relative to adults, children engaged lateral OFC more strongly for negative
      relative to positive feedback. These results indicate that children may find
      negative feedback more aversive than adults do. In summary, children aged 9-12
      years and adults recruit similar brain regions during risk-estimation and
      feedback processing, but some key differences between the groups provide insight
      into the factors contributing to developmental changes in decision-making.

PMID- 16574169
TI  - Liking and exposure: first, second and tenth time around.
AB  - The future liking may be poorly predicted from hedonic ratings in first exposure.
      The stability of hedonic ratings as a function of differences in number of
      exposures was studied. 80 subjects (70 females; age=17-59 years, mean=25.5 years,
      S.D.=6.7 years) performed hedonic rating of 9 different stimuli (vanilla-flavored
      yogurts), all of which were different in sensory properties. Yogurts varied
      systematically in three experimental factors: total protein, sugar and vanilla
      flavor concentration. In first exposure, yogurts high in sweetness and with low
      vanilla intensity were rated as most liked. Subjects were divided in two equal
      groups of 40 persons and exposed to the stimuli different numbers of times: two
      and ten. There were no significant differences in changes of liking ratings
      between the two groups. Results indicate that liking of yogurts, traditionally
      eaten for breakfast in Denmark, measured by groups is relatively stable over
      exposures. However, summarizing results over groups covers that there are large
      individual differences in changes of liking ratings. 11.6% of the 720 analyzed
      changes in liking ratings were larger that 7.5 cm, corresponding to half the size
      of the scale.

PMID- 16574170
TI  - Reproductive suppression in subordinate female highveld mole-rats (Cryptomys
      hottentotus pretoriae): no role for endogenous opioid peptides.
AB  - The influence of endogenous opioid peptides (EOPs) on plasma luteinizing hormone
      (LH) levels in subordinate female highveld mole-rats (Cryptomys hottentotus
      pretoriae) was investigated to elucidate the physiological mechanisms responsible
      for inhibiting their gonadotropin-releasing hormone (GnRH) and/or LH release. The
      opioid antagonist naloxone was administered either alone or with GnRH. A single
      injection of naloxone failed to alter plasma LH levels in dominant reproductive
      females or in subordinate non-reproductive females in the presence or absence of
      their ovaries. Pituitary sensitivity to a GnRH challenge was not influenced by
      naloxone administered acutely or according to longer-term regimens in any of the
      treatment groups. The results suggest no role for EOPs at the level of the
      pituitary or hypothalamus in the socially induced infertility evident in non
      reproductive female highveld mole-rats.

PMID- 16574171
TI  - The suitability of a caffeinated energy drink for night-shift workers.
AB  - Past research has indicated that caffeinated 'functional energy drinks' (FEDs)
      are effective in counteracting sleepiness. It is not known however, what impact
      FEDs have on sleep itself. FEDs contain several active ingredients, including
      caffeine. They may therefore impact negatively on sleep and hence subsequent
      performance, deeming their use counterproductive. In a randomised cross-over
      design, 15 young adults participated in a simulated first night-shift protocol
      with 2 conditions, Functional Energy Drink (FED) and Non Functional Energy Drink
      (NonFED). Both involved a period of extended wakefulness (0700-0730 h-24.5 h)
      followed by an 8-h daytime 'recovery' sleep (0730-1530 h). During the FED
      condition, a commercially available FED was administered twice during the night.
      Sleepiness was assessed during the period of extended wakefulness and for a
      further 6h after waking. Sleep periods were recorded using a standard 5 channel
      polysomnogram. Comparison of the sleep periods showed that sleep onset latency
      remained unchanged as did stage 2 and slow wave sleep. Total sleep time however,
      was 29.1 min shorter (p<.05) in the FED condition. Sleep efficiency was also
      significantly reduced from 91.8+/-.9% to 84.7+/-2.7% (p<.05). It is evident that
      the residual effects of the FED's active ingredients impact on some aspects of
      daytime sleep following a simulated night-shift. Subsequent performance however
      was unaffected. The results deem FEDs to be effective for a single night-shift
      and warrant investigation into their use over successive night-shifts.

PMID- 16574172
TI  - To eat or not to eat; regulation by the melanocortin system.
AB  - The central melanocortin (MC) system is one of the best-characterized
      neuropeptidergic systems involved in the regulation of energy balance. This short
      review describes the role of the central MC system in feeding behavior.
      Pharmacological, anatomical and genetic studies show that activation of the MC
      system reduces meal size, whereas de-activation of the MC system increases meal
      size. Several brain regions, including distinct hypothalamic nuclei and the
      hindbrain, are involved in this process. Further dissection of MC pathways in
      feeding behavior is the subject of recent and probably future studies. As the MC
      system is involved in animal models of obesity and (possibly) anorexia, it
      appears that this is a target system for development of drugs for the treatment
      of disturbed human eating behavior.

PMID- 16574173
TI  - Identification of very long chain fatty acids from sugar cane wax by atmospheric
      pressure chemical ionization liquid chromatography-mass spectroscopy.
AB  - A method is described for the enrichment of very long chain fatty acids (VLCFAs)
      from total fatty acids of sugar cane wax and their identification as picolinyl
      esters by means of liquid chromatography-mass spectrometry with atmospheric
      pressure chemical ionization (LC-MS/APCI). The method is based on the use of
      preparative reversed phase HPLC of 100 mg amounts and their subsequent
      identification by microbore APCI LC-MS. The combination of these two techniques
      was used to identify unusual saturated VLCFAs up to C(50).

PMID- 16574174
TI  - Effect of age on germination of dormant seeds.
AB  - Dormant seeds in permanent soil seed banks change their germination probability
      with age, but little is known about the causes of this behavior. Since current
      adaptive models do not consider the age structure of the seed bank, the sole
      explanation is that changes in germination probability with age are due to
      passive accidental factors or to decay of seeds. Here we present a theory, which
      shows that such changes might be adaptive. In particular, in density-regulated
      populations, the evolutionarily stable fraction of germinating seeds in each age
      class increases with age whenever age-dependent mortality of dormant seeds
      remains constant or increases with age.

PMID- 16574175
TI  - Comparison of indirect and direct approaches using ion-trap and Fourier transform
      ion cyclotron resonance mass spectrometry for exploring viperid venom proteomes.
AB  - In a sense, the field of snake venom proteomics has been under investigation
      since the very earliest biochemical studies where it was soon recognized that
      venoms are comprised of complex mixtures of bioactive molecules, most of which
      are proteins. Only with the re-emergence of 2D polyacrylamide gel electrophoresis
      (2D PAGE) and the recent developments in mass spectrometry for the
      identification/characterization of proteins coupled with venom gland
      transcriptomes has the field of snake venom proteomics began to flourish and
      provide exciting insights into the protein composition of venoms and subsequently
      their pathological activities. In this manuscript we will briefly discuss the
      state of snake venom proteomics followed by the presentation of several
      straightforward experiments designed to explore approaches to investigating venom
      proteomics. The first set of experiments used 1D gel electrophoresis (1D PAGE) of
      Crotalus atrox venom followed by slice-by-slice analysis of the proteins using
      liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). In the
      second set of experiments, C. atrox and Bothrops jararaca venoms were subjected
      to in-solution digestion followed by Fourier transform ion cyclotron resonance
      (FTICR) LC/MS/MS. The peptide ion-maps of these venoms were compared along with
      the proteins identified. In addition, the results were compared to the results
      observed from the 1D PAGE approach. From these studies it is clear that sample de
      complexation/fractionation before mass spectrometry is still the best approach
      for maximum proteome coverage. Furthermore, comparison of venom proteomes based
      on tryptic peptide identities between the proteomes is not particularly effective
      since there does not appear to be a sufficient number of such identical peptides,
      derived from related proteins, present in venoms. Finally, as has previously been
      recognized without either better databases of venom protein sequences or facile
      and rapid de novo sequencing technologies for mass spectrometry, snake venom
      proteome investigation will remain a laborious task.

PMID- 16574176
TI  - Fourier transform mass spectrometry: a powerful tool for toxin analysis.
AB  - The crude venom of Conus virgo was analyzed by Fourier transform mass
      spectrometry (FTMS) using both nano-electrospray ionization and MALDI. The
      analyses were performed directly on the crude venom, without chromatographic
      separation. The mass fingerprinting of the venom yielded 64 distinct molecular
      masses in the range 500-4500 Da with two major components at 1328.5142 and
      1358.5592 Da. To facilitate the de novo sequencing of these compounds, the
      disulfide bonds of all components were reduced for the whole venom. The mass
      accuracy, resolution and sensitivity provided by FTMS were necessary to complete
      the sequencing of the two new peptides named ViVA and ViVB, that turned out to be
      conotoxins belonging to the T-superfamily, with the disulfide framework V. The
      peptides shared 80% similarity and as often observed for this class of compound,
      they were highly post-translationally modified: amidated C-terminus, pyroglutamic
      acid residue at the N-terminus and two disulfide bonds. Complementary online nano
      LC-nano-ESI-FTMS experiments were undertaken. Among the 130 molecular masses
      found in the coupling experiments, only 45 were common with those obtained in the
      direct approach, which means that 21 compounds observed by nano-ESI-FTMS were not
      detected. This clearly shows that some discriminations against some classes of
      compounds occur when a chromatographic step is used before mass spectrometry.

PMID- 16574177
TI  - Venom landscapes: mining the complexity of spider venoms via a combined cDNA and
      mass spectrometric approach.
AB  - The complexity of Australian funnel-web spider venoms has been explored via the
      combined use of MALDI-TOF mass spectrometry coupled with chromatographic
      separation and the analysis of venom-gland cDNA libraries. The results show that
      these venoms are far more complex than previously realized. We show that the
      venoms of Australian funnel-web spiders contain many hundreds of peptides that
      follow a bimodal distribution, with about 75% of the peptides having a mass of
      3000-5000 Da. The mass spectral data were validated by matching the
      experimentally observed masses with those predicted from peptide sequences
      derived from analysis of venom-gland cDNA libraries. We show that multiple
      isoforms of these peptides are found in small chromatographic windows, which
      suggests that the wide distribution of close molecular weights among the
      chromatographic fractions probably reflects a diversity of structures and
      physicochemical properties. The combination of all predicted and measured
      parameters permits the interpretation of three-dimensional 'venom landscapes'
      derived from LC-MALDI analysis. We propose that these venom landscapes might have
      predictive value for the discovery of various groups of pharmacologically
      distinct toxins in complex venoms.

PMID- 16574178
TI  - A neurotoxic phospholipase A2 variant: isolation and characterization from
      eastern regional Indian cobra (Naja naja) venom.
AB  - CM-Sephadex C-25 column chromatography profile of Indian cobra (Naja naja) venom
      from eastern region showed a distinct and a dominant phospholipase peak, peak-10,
      while it was not seen in either southern or western venom samples. Peak-10 was
      subjected to CM-Sephadex C-25 and Sephadex G-50 column chromatography to isolate
      NN-X-PLA(2). NN-X-PLA(2) is a single chain protein with the relative molecular
      weight of 10kDa by SDS-PAGE. It was toxic to mice with an LD(50) value 0.098
      mg/kg body weight (i.p.) and the mice exhibited acute neurotoxic symptoms. Upon
      indirect stimulation, it inhibited the twitching of frog's gastrocnemius muscle
      in a dose dependent manner. NN-X-PLA(2) was weakly anticoagulant and devoid of
      cytotoxicity, myotoxicity, hemorrhage, edema inducing, and directlytic activities
      and effects on platelet aggregation process. Upon chemical modification
      independently with p-bromophenacyl bromide and acetic anhydride, NN-X-PLA(2) lost
      both enzymatic and toxic properties.

PMID- 16574179
TI  - Epidemiological and clinical characteristics of scorpionism in Colima, Mexico
      (2000-2001).
AB  - We analyzed 13,223 clinical records of patients treated for scorpion sting in
      hospitals of the Mexican Institute of Public Health and the Ministry of Health in
      the state of Colima, Mexico, during the years 2000-2001. A database containing
      demographic, epidemiological and clinical information was constructed and
      analyzed retrospectively. Patients were classified in the categories as mild
      (49.2%), moderate (33.8%) and severe (17.0%) according to commonly accepted
      standards. Most common symptoms recorded were local pain (94.7%), local
      paresthesia (67.2%), pruritus/itching (54.3%), sensation of a lump or hair in the
      throat (47.3%), and sialorrhoea (27.7%). The median time from sting to admission
      to the emergency room (patient delay) was 33min (interquartile range: 12-60). We
      found that older and clinically severe patients were significantly associated
      with longer times of admission to the emergency room. Age was significantly
      associated with clinical severity: the age group 0-10 years included a higher
      proportion of severe cases than the group 11 years and older. In four cases,
      patients died. An educational campaign to inform the population about the
      importance of receiving prompt attention following a scorpion sting has potential
      value in reducing complications in the emergency room.

PMID- 16574180
TI  - Verified bites by the woodlouse spider, Dysdera crocata.
AB  - Bites by the woodlouse spider, Dysdera crocata, are virtually innocuous. The main
      symptom is minor pain, typically lasting less than 1h, probably due mostly to
      mechanical puncture of the skin. However, because the spider has a strong
      proclivity to bite, has large fangs which it bares when threatened and is
      commonly mistaken for the medically important brown recluse spider in the United
      States, documentation of the mild effects of its bites may prevent excessive,
      unwarranted and possibly harmful treatment. We present information on eight
      verified bites reported to us as well as eight additional bites recorded in the
      literature.

PMID- 16574181
TI  - Screening for post-translational modifications in conotoxins using liquid
      chromatography/mass spectrometry: an important component of conotoxin discovery.
AB  - Mass spectrometry has emerged as an important technique for conotoxin analysis
      due to its capacity for selective, sensitive, information-rich analyses. Using
      liquid chromatography/mass spectrometry, Conus venom can be fractionated and the
      peptides surveyed for specific post-translational modifications, indicating those
      toxin components likely to have an important biological function. With Conus
      striatus and Conus victoriae venom as models, bromination, carboxylation and
      glycosylation modifications are identified through characteristics such as
      isotopic distribution and labile losses observed during mass spectrometric
      analysis. This modification screening approach enables the identification of a C.
      victoriae bromo-carboxy-conotoxin, designated vc5c, as a candidate for detailed
      mass spectrometric analysis. Using a cDNA sequence coupled with liquid
      chromatography/mass spectrometry and nanoelectrospray ionization-ion trap-mass
      spectrometry, the sequence of vc5c is determined to be ICCYPNXWCCD, where W is 6
      bromotryptophan, X is gamma-carboxy glutamate and C is disulfide-linked cysteine.
      This represents the ninth T-superfamily (-CC-CC- scaffold) toxin that has been
      isolated from venom and characterized.

PMID- 16574182
TI  - Ultrasound velocity in human muscle in vivo: perspective for edema studies.
AB  - The present study examines the association of the changes in ultrasound velocity
      measured at 1 MHz using 1.5 micros duration tone burst in the human soleus muscle
      in vivo with several pathologies including patients with chronic renal failure
      (CRF) and disorders of the cardiovascular system. Total 127 subjects were
      investigated, with approximately equal number of male and female subjects
      uniformly distributed by age, from 15 to 70 years old. Since molecular
      composition of the tissue is thought to have greater effect on the bulk
      ultrasound velocity, potential contribution of both water and fat, two main
      variable components of a muscle, were taken into account. Observed negative
      correlation of ultrasound velocity with the body mass index was considered a
      result of an elevated fat content. Based on the obtained data, presence of leg
      edemas results in a measurably lower ultrasound velocity in the soleus muscle.
      Unless patients had visibly detected leg edema, no difference between healthy
      individuals, patients with chronic heart failure, or CRF was found. Despite
      relatively high individual variations in velocity, ranging from 1530 to 1615 m/s,
      a statistically significant gender correlated difference between average values
      of the velocity was observed. No dependence of velocity on subject age was
      detected. An indirect confirmation of the muscle fluid homeostasis was revealed
      in patients with CRF undergoing hemodialysis procedure. After hemodialysis, a
      significantly smaller increase (0.3% in average) of ultrasound velocity in the
      soleus muscle was observed than otherwise could be expected if a uniform relative
      loss of total body fluids was assumed (1-1.3%). In general, the study findings
      set a premise for using ultrasound velocity as a potential quantitative parameter
      for edema assessment.

PMID- 16574183
TI  - Characterization of the cellular receptors for the South American hemorrhagic
      fever viruses Junin, Guanarito, and Machupo.
AB  - The New World arenaviruses Junin, Machupo, and Guanarito are the causative agents
      of hemorrhagic fevers (HF) with high mortality in humans. The cellular receptor
      for Old World arenaviruses and one subgroup of the New World arenaviruses (Clade
      C) have been identified as alpha-dystroglycan (alpha-DG). In contrast, the
      receptor(s) of the South American HF viruses, which belong to the Clade B New
      World arenaviruses, are currently unknown. To begin to characterize the cellular
      receptors used by these pathogens, we generated recombinant retroviral
      pseudotypes with the glycoproteins of Guanarito, Junin, and Machupo. Infection
      with the South American HF viruses is independent of alpha-DG and functional
      receptors for Guanarito, Junin, and Machupo were found on most human cell types
      and cells derived from non-human primate and rodents. Guanarito, Junin, and
      Machupo share a common receptor, which is distinct from the receptor(s) used by
      the closely related non-pathogenic Clade B virus Amapari, and the genetically
      more distant Clade A and C New World arenaviruses. We show that the cellular
      receptor(s) for the South American HF viruses are proteins or protein-linked
      entities and that infection is not dependent on protein-linked N-glycans, O
      glycans, or glycosaminoglycans.

PMID- 16574184
TI  - Genomic characterization of the unclassified bovine enteric virus Newbury agent-1
      (Newbury1) endorses a new genus in the family Caliciviridae.
AB  - The pathogenic bovine enteric virus, Newbury agent-1 (Bo//Newbury1/1976/UK),
      first identified in 1976, was characterized as a possible calicivirus by
      morphology, buoyant density in CsCl and the presence of a single capsid protein
      but genomic sequence could not be obtained. In the present study, the complete
      genome sequence of Newbury1 was determined and classified Newbury1 in a new genus
      of the Caliciviridae. The Newbury1 genome, of 7454 nucleotides, had two predicted
      open reading frames (ORFs). ORF1 encoded the non-structural and contiguous capsid
      proteins. ORF2 encoded a basic protein characteristic of the family
      Caliciviridae. Compared to the 4 recognized Caliciviridae genera, Norovirus,
      Sapovirus, Lagovirus and Vesivirus, Newbury1 had less than 39% amino acid (47%
      nucleotide) identity in the complete 2C-helicase, 3C-protease, 3D-polymerase and
      capsid regions but had 89% to 98% amino acid (78% to 92% nucleotide) identity to
      the recently characterized NB virus in these regions. By phylogenetic analyses,
      Newbury1 and NB viruses formed a distinct clade independent of the 4 recognized
      genera. However, amino acid identities showed that Newbury1 and the NB virus were
      distinct polymerase types (90% amino acid identity), but their complete capsid
      proteins were almost identical (98% amino acid identity). Analyses of
      contemporary viruses showed that the two polymerase genotypes, Newbury1 and NB,
      were circulating in UK cattle and antibody to Newbury1-like viruses was common in
      cattle sera. The present study defined the existence of a new genus in the
      Caliciviridae that we propose be named Becovirus or Nabovirus to distinguish the
      new clade from bovine noroviruses.

PMID- 16574185
TI  - Identification of a specific gene expression pattern associated with HCV-induced
      pathogenesis in HCV- and HCV/HIV-infected individuals.
AB  - Gene expression profiling was performed on liver biopsies from 28 patients (12
      HCV and 16 HCV/HIV infected) in an attempt to understand the mechanisms of HCV
      liver disease in the presence and absence of HIV coinfection. The data were
      compared with clinical observations and a gene expression database obtained for
      transplant HCV-infected samples. This is the first report of functional genomics
      being used to compare intrahepatic gene expression profiles of HCV- and HCV/HIV
      infected individuals. Significantly, the intrahepatic global gene expression
      profiles do not differ between HCV- and HCV/HIV-infected individuals. However, a
      subset of patients was identified who share a specific pattern of gene
      expression, termed the enhanced gene expression (EGE) pattern. Specifically, the
      EGE (+) patients show a dramatic decreased expression of multiple genes
      associated with the FAS-apoptosis pathway and increased expression of lymphocyte
      adhesion molecules and lymphocyte-specific genes. The EGE (+) patients also have
      partially impaired Type I and II IFN-mediated antiviral responses, including a
      lack of induction of the anti-fibrogenic cytokine IFN-gamma. Importantly, the
      pattern of gene expression observed in EGE (+) patients has similarities to
      patients who developed fibrosis within 1 year of receiving a liver transplant.

PMID- 16574186
TI  - Genome sequence and molecular characterization of Homalodisca coagulata virus-1,
      a novel virus discovered in the glassy-winged sharpshooter (Hemiptera:
      Cicadellidae).
AB  - The complete nucleotide sequence of a novel single-stranded RNA virus infecting
      the glassy-winged sharpshooter, Homalodisca coagulata, has been determined. In
      silico analysis of H. coagulata virus-1 (HoCV-1) revealed a 9321-nt
      polyadenylated genome encoding two large open reading frames (ORF1 and ORF2)
      separated by a 182-nt intergenic region (IGR). The deduced amino acid sequence of
      the 5'-proximal ORF (ORF1, nt 420-5807) exhibited conserved core motifs
      characteristic of the helicases, cysteine proteases, and RNA-dependent RNA
      polymerases of other insect-infecting picorna-like viruses. A structural model
      created using Mfold exposed a series of stem loop (SL) structures immediately
      preceding the second ORF which are analogous to an internal ribosome entry site
      (IRES), suggesting that ORF2 begins with a noncognate GCA triplet rather than the
      canonical AUG. This 3' ORF2 (5990-8740) showed significant similarity to the
      structural proteins of members of the family Dicistroviridae, particularly those
      belonging to the genus Cripavirus. Evidence demonstrating relatedness of these
      viruses regarding genome organization, amino acid sequence similarity, and
      putative replication strategy substantiate inclusion of HoCV-1 into this
      taxonomic position.

PMID- 16574187
TI  - Factorial experimental design of winery wastewaters treatment by heterogeneous
      photo-Fenton process.
AB  - Winery wastewaters are difficult to treat by conventional biological processes
      because they are seasonal and experience a substantial flow variations.
      Photocatalytic advanced oxidation is a promising technology for wastewaters
      containing high amounts of organic matter. In this work, the photo-Fenton process
      in heterogeneous phase is presented as an alternative methodology for the
      treatment of winery wastewaters. As a consequence of the great number of existing
      variables, an experimental design methodology has been used in order to study the
      influence and interaction of various variables and to obtain a reduced empirical
      model which describes the organic matter degradation process. Applying photo
      Fenton treatment in heterogeneous phase under energetic conditions for synthetic
      samples simulating winery wastewaters results in purification levels of up to 50%
      (measured as total organic carbon). Different reduced models are obtained and
      their utilization depends mainly on the degree of degradation of organic matter
      required.

PMID- 16574188
TI  - Persistent organic pollutants (POPs) in the conventional activated sludge
      treatment process: model predictions against experimental values.
AB  - The FATE and treatibility estimator (FATE) model, developed by the United States
      Environmental Protection Agency was used for the prediction of the FATE of 26
      persistent organic pollutants (POPs), i.e. 7 PCBs and 19 organochlorine compounds
      (OCs), during the conventional activated sludge treatment process applied in the
      waste water treatment plant (WWTP) of Thessaloniki, Greece. The removal rates
      predicted by the model for the primary and the secondary treatment stages were
      found to differ substantially from those experimentally measured. When the
      overall treatment was considered, the differences between measured and model
      predicted removals were within acceptable limits of confidence. Possible reasons
      that might cause deviations from experimental values were suggested to be the
      wastewater content in dissolved organic carbon (DOC), and/or the low
      concentrations of POPs in untreated wastewater.

PMID- 16574189
TI  - Do herbicide treatments reduce the sensitivity of mosquito larvae to
      insecticides?
AB  - Invasive mosquitoes are economic and sanitary concerns especially in Europe and
      America. Most work has emphasized the role of resistance [Berrada, S., Fournier,
      D., Cuany, A., Nguyen, T.X., 1994. Identification of resistance mechanisms in a
      selected laboratory strain of Cacopsylla pyri (Homoptera: Psyllidae): altered
      acetylcholinesterases and detoxifying oxidases. Pesticide Biochemistry and
      Physiology 48, 41-47; Hemingway, J., Hawkes, N.J., McCarroll, L., Ranson, H.,
      2004. The molecular basis of insecticide resistance in mosquitoes. Insect
      Biochemistry and Molecular Biology 34, 653-665] to insecticides. Compounds acting
      on larval sensitivity to insecticides are not well studied and their action
      remains poorly understood. Among several residual chemicals in ecosystems,
      particularly in wetlands, we identified a possible interaction of an herbicide on
      larval resistance to an insecticide. Our work contributes to the global control
      of mosquito populations by identifying possible pathways of resistance to
      insecticides of these vectors. Resistance or tolerance to insecticide treatments
      might contribute to successful invasion by mosquitoes. Here we report an
      ecotoxicological approach to test the hypothesis of an indirect effect of
      atrazine on mortality of an invasive vector. A brief contact (48h) between Aedes
      aegypti mosquito larvae and atrazine led to a modification of larval sensitivity
      to an insecticide: using atrazine as an inducer led to a decrease in the
      mortality of larvae treated with Bacillus thuringiensis var. israelensis (Bti).

PMID- 16574190
TI  - Reproduction obstacles for the female green neon shrimp (Neocaridina denticulata)
      after exposure to chlordane and lindane.
AB  - The purpose of this study was to investigate the effects of chlordane and lindane
      on reproduction obstacles and endocrine disruption in female green neon shrimp
      (Neocaridina denticulata). Individuals of N. denticulata, a common inhabitant of
      freshwater systems in Taiwan, was exposed to different levels of chlordane (1 and
      10 ngl(-1)) and lindane (0.1 and 1 microgl(-1)). The reproductive ability and
      reproductive hormone levels were observed after exposure. According to our
      findings, an increase in estrogen, induction of a vitellogenin-like protein, and
      changes in reproductive performance were observed in both chlordane- and lindane
      treated shrimp. Thus, it was concluded that chlordane and lindane may cause some
      reproduction obstacles and disruption of endocrine functions in N. denticulata.

PMID- 16574191
TI  - Study of the presence of pesticides in surface waters in the Ebro river basin
      (Spain).
AB  - This work studies the presence of a total number of 44 substances found in waters
      of the Ebro river basin (Spain), all included in the Pesticides Control Network,
      whose purpose is to monitor diffuse pollution of surface waters caused by
      pesticides contained in some of the dangerous substances lists established in
      existing legislation and their high degree of use in the basin. Most of the
      pesticide sampling points are located in the sections of river that receive run
      off waters from various agricultural areas shortly before opening out onto the
      main river (the Ebro), in areas of special agricultural importance. Water samples
      are subjected to a solid-liquid extraction as a previous step to their analysis
      by GC/MS (gas chromatography/mass spectrometry). Pesticides most frequently found
      and in greater concentrations in the waters of the Ebro river basin are 3,4
      dichloroaniline, molinate, desethylatrazine, dimetoate, simazine, atrazine,
      metolachlor and chlorpyrifos. There are certain compounds that are not detected
      or their concentrations are below the quantification limit, such as 4
      isopropylaniline, ametryn, beta-HCH, delta-HCH, aldrin, isodrin, dieldrin,
      heptachlor epoxide, endosulfan and endosulfan-sulfate. Diuron appears at specific
      points in some of the stations.

PMID- 16574192
TI  - Retention of Cd, Zn and Co on hydroxyapatite filters.
AB  - This study qualifies and quantifies the immobilization of Cd, Zn and Co, (used as
      models of bivalent metal ions due to their relevant toxicity) in filters of
      synthetic hydroxyapatite (HAP) [Ca5(PO4)3OH]. They were flushed with solutions
      containing Cd (1 x 10(-5)M), Zn and Co (1 x 10(-4)M) at constant pH (8.6) and
      ionic strength (0.01 M). The concentration of these metal ions in the outlet was
      measured by ICP-OEM spectroscopy. The software PHREEQC (version 2.4.2) was used
      to model sorption process and the potential effect of salinity (KCl), pH,
      alkalinity (NaHCO3) and hardness (CaCl2) over the efficiency of the treatment.
      Results showed an excellent retention capacity of HAP for Cd, Zn and Co. Sorption
      data were successfully described considering a mix model of surface complexation
      onto phosphate surface groups, ionic exchange in surface calcium sites and the
      precipitation of ZnO. Co exchange and surface complexation constants (Kex and Kc)
      were taken from previous experiments, while KexCd=0.32 and KcCd=0.63 were
      estimated from our modeling results. Predictive values of metal ion sorption show
      that: (a) an increase in hardness does not play a significant role in the
      retention capacity of these metals on HAP; (b) an increase in alkalinity promotes
      the precipitation of MeCO3 which could alter the hydrodynamic of the column; (c)
      a decrease in pH and an increase in salinity inhibit ZnO precipitation enhancing
      Zn and Cd adsorption and decreasing Co retention on HAP.

PMID- 16574193
TI  - Drip-feed bioreactor for the treatment of concentrated wastes with minimal
      dilution.
AB  - Avoiding substrate inhibition is a significant challenge in designing biological
      treatment systems for concentrated or toxic wastes. Substrate inhibition is
      commonly avoided by diluting the waste before treatment, however, dilution of a
      waste before treatment is not always feasible. In the case of radioactive mixed
      wastes and chemical warfare materiel (CWM), dilution presents regulatory and
      safety concerns. In this study, we investigated a "drip-feed" reactor
      configuration as an alternative approach for the biological treatment of
      concentrated waste streams with minimal dilution and complete containment. In the
      drip-feed reactor undiluted waste is slowly fed to biomass in a reactor at a rate
      sufficient to maintain activity, but at a low enough rate so that bacterial
      degradation maintains the reactor concentration below the toxic threshold. The
      reactor has no effluent, but rather fills as the undiluted waste is fed to the
      reactor, which has the advantage of preventing the release of hazardous material
      into the environment during treatment. Volatile releases are prevented with the
      use of condensers. The drip-feed bioreactor configuration was tested under
      aerobic conditions, at 25 degrees C, using a 10% acetonitrile feed solution. The
      treatment of acetonitrile to less than 0.1 mg l(-1) was achieved with a dilution
      factor of only 3.4. The acetonitrile degradation reaction was pH sensitive, where
      the optimal pH range for the biodegradation process was approximately between 6.5
      and 7.1 and the biodegradation rate declined precipitously above pH 7.2. The
      applicability of the drip-feed reactor configuration to the treatment of mixed
      wastes and CWM is discussed.

PMID- 16574195
TI  - Metabolic syndrome and age-related dementia: endocrinological aspects of
      adaptation to aging.
AB  - Metabolic syndrome is one of the determinants of lifespan in Japan. In order to
      prevent the acute vascular events, intervention is recommended. However,
      management of patients with this syndrome increased the number of patients with
      cognition decline and depressive state. Endocrinological studies with human and
      experimental animals showed that there is a negative relationship between
      progression of metabolic syndrome and occurrence of mental disorders. In this
      review, we summarize our clinical and experimental data, and discuss on the
      mechanism of the metabolic syndrome prevention of progression of age-related
      mental disorder.

PMID- 16574194
TI  - A longitudinal study of the effect of GSTT1 and GSTM1 gene copy number on
      survival.
AB  - Deletions of the glutathione S-transferase superfamily genes GSTT1 and GSTM1 has
      been associated with oxidative stress related diseases and recently explored as
      factors implicated in longevity as well. Reported results have been conflicting,
      which may partially be caused by the traditional use of assays unable to
      discriminate between carriers of one or two functional genes. Using a
      quantitative realtime PCR method facilitating quantification of gene copy number,
      we evaluated the influence of GSTT1 and GSTM1 gene deletions on longevity in a
      longitudinal study of 681 elderly Danish twins. The mean follow-up time was 7.6
      years and during this time a total of 294 deaths occurred. The results
      demonstrated a non-significant trend for carriage of two copies of the GSTM1
      functional gene to be a protective factor, whereas both heterozygosity and
      homozygosity for the GSTT1 functional gene was associated with a moderate but
      significant increased mortality in women (hazard rate 2.46 (CI95: 1.43-4.23) and
      2.22 (CI95: 1.25-3.94) for one and two alleles, respectively). To our knowledge,
      this is the first longitudinal study exploring the influence of GST gene
      polymorphisms on longevity and these data implies that GST gene copy numbers do
      affect mortality risk in the elderly.

PMID- 16574196
TI  - Risk-based ecological soil quality criteria for the characterization of
      contaminated soils. Combination of chemical and biological tools.
AB  - This paper describes the development of soil quality criteria for the
      characterization of soils focused on the potential risk to the ecosystem. The
      approach combines both Generic Soil Quality standards (GSQs) for individual
      chemicals and direct ecotoxicity assays on soil samples taken from the site.
      Criteria establish three main risk levels with their corresponding trigger
      values. The trigger values to determine high risk or "polluted" soils are
      exclusively based on direct toxicity assessments. The trigger values for the
      other categories are established by a combination of the application of GSQs and
      the results of bioassays. Low-risk is assumed when no toxicity is observed and
      GSQs based on precautionary ecotoxicity thresholds are not exceeded; high-risk
      must be considered if acute toxicity above the proposed trigger value is observed
      in soil or leachate samples. In between these levels, the risk cannot be
      elucidated and a site-specific assessment is required. The GSQs take into account
      the current or future land use, thus defining three categories: industrial soils,
      urban/residential soils and natural/agricultural/forest soils, each of them with
      different ecological requirements. The GSQ values are established following an
      inverse risk assessment methodology, integrating ecotoxicity and exposure models
      and setting the soil levels associated to pre-established criteria for the
      assumption of low risk. The proposed methodology covers all relevant ecological
      receptors and processes, soil organisms, potential contamination of ground and
      surface waters, and exposure of terrestrial vertebrates due to bioaccumulation
      and biomagnification. Exposure routes and protection criteria are defined in each
      protection goal. The relevance of each receptor and route is established
      according to the land use.

PMID- 16574197
TI  - Application of the photo-Fenton process to the treatment of wastewaters
      contaminated with diesel.
AB  - The application of the photo-Fenton process for the treatment of wastewaters
      contaminated with diesel oil was investigated. This particular process has been
      widely studied for the photochemical degradation of highly toxic organic
      pollutants. Experiments were performed according to a factorial experimental
      design at two levels and two variables: H(2)O(2) concentration (5-200 mM) and
      Fe(2+) concentration (0.01-1 mM). Experimental results demonstrated that the
      photo-Fenton process is technically feasible for the treatment of wastewaters
      containing diesel oil constituents, with total mineralization. A combination of
      factorial experimental design and gradient descent techniques was employed to
      optimize the amount of the Fenton reagents, resulting in Fe(2+) (0.1 mM) and
      H(2)O(2) (50 mM). These optimized levels did not exceed the limit for disposal of
      ferrous ions (0.27 mM) proposed at the local environmental legislation.

PMID- 16574198
TI  - A new methodology for cost-effectiveness studies of domestic radon remediation
      programmes: quality-adjusted life-years gained within primary care trusts in
      central England.
AB  - Radon is a naturally occurring radioactive gas, high levels of which are
      associated with geological formations such as those found in Northamptonshire and
      North Oxfordshire in the UK. The UK's National Radiological Protection Board have
      designated both districts as radon Affected Areas. Radiation levels due to radon,
      therefore, exceed 200 Bq m(-3), the UK's domestic Action Level, in over one
      percent of domestic properties. Because of radon's radioactivity, exposure to the
      gas can potentially cause lung cancer, and has been linked to some 2000 deaths a
      year in the UK. Consequently, when radiation levels exceed the Action Level,
      remediation against radon's effects is recommended to householders. This study
      examines the cost-effectiveness of remediation measures in Northamptonshire and
      North Oxfordshire by estimating cost per quality-adjusted life-year gained in
      four Primary Care Trusts, organisations that play a key public health policy role
      in the UK's National Health Service. The study is the first to apply this
      approach to estimating the cost-effectiveness of radon remediation programmes.
      Central estimates of cost per quality-adjusted life-year in the four Primary Care
      Trusts range from 6143pounds to 10323pounds. These values, when assessed against
      generally accepted criteria, suggest the remediation programmes in the trusts
      were cost-effective. Policy suggestions based on the estimates, and designed to
      improve cost-effectiveness further, are proposed for the four Primary Care Trusts
      and the UK's National Health Service.

PMID- 16574199
TI  - Evidence for the transfer of polychlorinated biphenyls, polychlorinated dibenzo-p
      dioxins, and polychlorinated dibenzofurans from soil into biota.
AB  - The concentrations of six indicator and co-planar polychlorinated biphenyls
      (PCBs), 17 polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans
      (PCDD/Fs) were determined in soil and associated biota samples collected from a
      polluted and wasted farmland in southern China. The sum of six indicator PCBs
      (Nos 28, 52, 101, 138, 153 and 180) concentrations in biota samples were
      proportional to the total amount of PCBs that transferred from soil to the
      corresponding biota samples, and the sum six indicator PCB congeners in samples
      were about 20% of the total PCBs, respectively. The ratios of the sum six
      indicator PCBs and the total PCBs in samples collected in the same area were
      approximately equal. The sums of six indicator PCBs were proportional to the
      total PCBs that transferred from soil to plant, while the co-planar PCBs were
      not. Analysis of individual PCB and PCDD/F congener signatures in soil revealed
      the original pollutant source after transportation and biodegradation for 14
      years using principal component analysis (PCA). The pattern of PCBs in soils and
      plants could reflect the original pollution source after transportation and
      biodegradation for 14 years, while the pattern of PCBs in the terrestrial animals
      could not reflect the primary source. The consumption foods in this region such
      as foraging chicken eggs, foraging duck eggs, and loach (Misgurnus
      anguillicaudatus) were highly contaminated, the total toxicity equivalent (TEQ)
      was up to 784 pg WHO-TEQ/g on basis lipid in foraging chicken eggs.

PMID- 16574200
TI  - Factor XIII in severe sepsis and septic shock.
AB  - OBJECTIVE: In sepsis, activation of coagulation and inhibition of fibrinolysis
      lead to microvascular thrombosis. Thus, clot stability might be a critical issue
      in the development of multiple organ dysfunction syndrome. Activated FXIII
      (FXIIIa) forms stable fibrin clots by covalently cross-linking fibrin monomers.
      Therefore, we investigated the impact of FXIII antigen and activity levels on
      disease severity and fatality in sepsis patients. PATIENTS AND METHODS: FXIII
      subunit A (FXIIIA) and FXIII cross-linking activity (FXIIICA) were measured in
      151 controls, in 32 patients with severe sepsis and 8 with septic shock. In
      addition, FXIII subunit B (FXIIIB) was measured in the sepsis patients. Moreover,
      clotting parameters were determined. RESULTS: Patients suffering from sepsis
      (n=40) had significantly (p<0.005) lower FXIIIA levels (median [range]: 36.5%
      [8.8-127.4%]) and FXIIICA levels (76.5% [9.4-266%]) as compared to healthy
      controls (n=151, 119% [31.3-283.2] and 122.4% [40.6-485.3], respectively). No
      difference in FXIIIA, FXIIIB and FXIIICA levels between survivors and non
      survivors, nor between patients with severe sepsis and septic shock was found.
      The specific activity of FXIII (FXIIICA/FXIIIA, SA(FXIII)) was significantly
      (p<0.001) higher in sepsis patients (2.0 [0.8-5.3]) as compared to healthy
      controls (1.0 [0.4-5.1]). SA(FXIII) significantly (p<0.05) increased with
      fatality (non-survivors [n=13] vs. survivors [n=27]: 3.3 [1.2-5.0] vs. 1.9 [0.8
      5.3]) and disease severity (septic shock vs. severe sepsis: 3.4 [1.8-4.3] vs. 1.9
      [0.8-5.3]). CONCLUSION: We show decreased FXIIICA and FXIIIA levels, but higher
      SA(FXIII) in sepsis as compared to controls. Increased SA(FXIII) correlates with
      disease severity and fatality in sepsis patients.

PMID- 16574201
TI  - Prophylaxis in rare coagulation disorders -- factor X deficiency.
AB  - Factor X (FX) is a vitamin K-dependent protease that plays a central role in the
      blood coagulation cascade. Deficiency of FX is one of the rarest congenital
      coagulation disorders, resulting in a variable clinical phenotype. The molecular
      basis for FX deficiency is characterised by a large number of gene mutations and
      polymorphisms. The Greifswald Registry of FX deficiency was started in 1998 and
      aims to investigate the relationship between genetic mutations and the clinical
      severity of the disease. To date, 34 of 102 patients have been treated for severe
      bleeding episodes or for surgical procedures. Only seven patients, six of whom
      are children, receive regular prophylaxis with Factor IX (FIX) concentrate (FIX
      HS, ZLB Behring; also containing approximately 800IU FX). In all cases, the
      bleeding episodes are well controlled without any serious treatment-related
      complications.

PMID- 16574202
TI  - Histopathological and ultrastructural effects of glycolic acid on rat skin.
AB  - Use of alpha hydroxy acids (AHA) to ameliorate specific dermatological problems
      with keratinization has become fairly widespread. The aim of this study was to
      evaluate the effects of the AHA derivative of glycolic acid, applied in different
      dosages, on rat skin using light and electron microscopy. Skin biopsies were
      taken from the dorsal side of rats (n=16) and at the end of each week after
      applying solutions containing AHA: week 1, 8% (n=5); week 2, 50% (n=5); week 3,
      70% (n=6). The skin samples were fixed in 10% formalin for histology and 2.5%
      glutaraldehyde solution for electron microscopy and processed using routine
      protocols. Histological sections were stained with hematoxylin and eosin (H&E),
      Masson's trichrome and were also labelled for binding of a primary antibody
      against collagen I using the avidin-biotin-peroxidase method. The epidermal
      thicknesses were measured and the fibroblast count of the dermis was taken and
      the results compared using the statistical ANOVA test. Semi-thin sections were
      stained with toluidine blue-azure II solution and ultrathin sections were
      contrasted with uranyl acetate and lead citrate. Histochemical and
      immunohistochemical observations demonstrated that AHA treatment resulted in
      statistically significant increased thickness of the epidermis and an increase in
      numbers of active fibroblasts and in the amount of dense collagen, especially at
      higher dosages of AHA. Ultrastructural examination of rat skin from AHA-treated
      groups showed cytoplasmic vacuolization in epidermal keratinocytes, intercellular
      dysjunctions, and increased quantities of organized bundles of collagen fibers in
      the dermis. The use of AHA in appropriate dosages has been found to play an
      important role in the treatment of specific skin disorders, however, the harmful
      effects of use of AHAs at higher concentrations should not be ignored. We
      conclude that alpha hydroxyl acids have a wide spectrum of use in the field of
      dermatology but, due to side-effects, their use, dosage, and time frame should be
      restricted to the advice of dermatologists.

PMID- 16574203
TI  - Characterization of neutropenic fever in patients receiving first-line adjuvant
      chemotherapy for epithelial ovarian cancer.
AB  - OBJECTIVES: Limited information is available on the incidence and characteristics
      of neutropenic fever (NF) in patients receiving contemporary regimens for
      epithelial ovarian cancer (EOC). We examined this issue in patients receiving
      first-line adjuvant chemotherapy with platinum- and paclitaxel-based regimens at
      a major cancer institute. METHODS: Charts of patients with EOC at a single
      institute from 1998 through 2002 were reviewed. Data were collected on the
      incidence and duration of NF, duration of hospitalization and fever, cultures,
      antibiotic and chemotherapy regimen, and type of debulking procedure. RESULTS:
      140 patients were treated for EOC. 125 patients received first line chemotherapy.
      15 episodes of NF were observed. Mean duration of neutropenia and fever was 2.33
      and 3.07 days respectively. 9 of 15 (60%) NF episodes occurred after cycle 1.
      Cultures were positive in 7 of 15 patients (47%). Organisms most frequently
      recovered were bowel-derived. 8 patients (53%) had bowel resections, and 15
      patients (100%) had radical or supraradical procedures. There was a correlation
      between incidence of NF and type of procedure (P = 0.01) and stage of EOC (P =
      0.04). There was no correlation between NF and elderly age, medical
      comorbidities, and postoperative complications. CONCLUSIONS: The rate of NF was
      higher than previously reported. NF occurred most frequently after cycle 1. NF
      patients were of advanced stage that had undergone more aggressive surgery and
      had bowel resections. Our data suggest that patients with advanced EOC who
      undergo more radical procedures should be identified as high risk for developing
      NF in early cycles.

PMID- 16574204
TI  - Alpha-lipoic acid modulates ovarian surface epithelial cell growth.
AB  - OBJECTIVE: The intracellular redox state plays an important role in controlling
      inflammation. Clinical and laboratory data suggest that inflammation can lead to
      tumor progression. We hypothesized that restoring intracellular redox control
      would inhibit inflammation and subsequently tumor progression. Our studies were
      designed to investigate the effect of alpha-lipoic acid (ALA), a naturally
      occurring antioxidant, on a key inflammatory signaling pathway and cell
      proliferation in normal and tumorigenic ovarian surface epithelial cells.
      METHODS: Normal and tumorigenic ovarian surface epithelial cells were isolated as
      described by Roby and coworkers [Roby KF, Taylor CC, Sweetwood JP, Cheng Y, Pace
      JL, Tawpik O, Persons DL, Smith PG, Terranova PF, Development of a syngeneic
      mouse model for events related to ovarian cancer. Carcinogen 2000;21 (4):585.
      [1]]. The effect of ALA on cellular function was measured in cell proliferation
      and apoptosis assays. p27(kip1) protein levels were measured by Western analysis.
      Activation of NF-kappaB dependent transcription was assessed in cell cultures
      transiently transfected with NF-kappaB controlled reporter constructs. RESULTS:
      Our results reveal that ALA selectively inhibits the growth of tumorigenic as
      compared to non-tumorigenic ovarian surface epithelial cells. The growth
      inhibitory effect of ALA is not due to induction of apoptosis but instead is
      associated with an increase in the half-life of the cyclin-dependent kinase
      inhibitor, p27(kip1). In parallel to the growth inhibitory effect, ALA also
      affects a key inflammatory signaling pathway by inhibiting TNFalpha-induced NF
      kappaB signaling activity. CONCLUSIONS: Our studies are the first to show that
      ALA treatment has a growth inhibitory effect on malignant surface epithelial
      cells of ovarian origin. We have also confirmed the reproducibility of the
      immunocompetent mouse ovarian cancer model originally described by Roby and
      coworkers [Roby KF, Taylor CC, Sweetwood JP, Cheng Y, Pace JL, Tawpik O, Persons
      DL, Smith PG, Terranova PF, Development of a syngeneic mouse model for events
      related to ovarian cancer. Carcinogen 2000;21 (4):585].

PMID- 16574205
TI  - Clinical impact of FDG-PET imaging in post-therapy surveillance of uterine
      cervical cancer: from diagnosis to prognosis.
AB  - OBJECTIVES: To evaluate the ability of whole-body 2-[(18)F]-fluoro-2-deoxy-d
      glucose (FDG) positron emission tomography (PET) scan to detect recurrent
      cervical cancer in women during follow-up after definitive treatment. METHODS: We
      retrospectively reviewed the whole-body FDG-PET scan of the women who had reached
      complete response after primary treatment for detection of recurrent cervical
      cancer between September 1, 2001 and October 31, 2004. RESULTS: One hundred
      twenty-one consecutive patients were registered for the current study and seventy
      six women were diagnosed as recurrence, twenty of which were asymptomatic. The
      FDG-PET scan detected 73 (96.1%) patients among 76 patients with recurrent
      disease and discriminated 38 (84.4%) patients among 45 patients without
      recurrence. The sensitivity, specificity and accuracy of the FDG-PET scan in
      assessment of recurrence among patients with cervical cancer were 96.1%, 84.4%
      and 91.7% respectively. Sixteen patients with no evidence of distant metastasis
      on FDG-PET scan received pelvic exenteration; complete response was achieved in 6
      (37.5%) patients, and all are alive with no evidence of disease. The FDG-PET scan
      detected FDG-avid lesions in 17 (85.0%) of the 20 asymptomatic patients with
      recurrent disease, and 8 (40.0%) patients received therapy with curative intent;
      complete response was achieved in five (25.0%) patients and all are alive with no
      evidence of disease. Three-year overall survival of this study was 85.6%.
      CONCLUSIONS: The whole-body FDG-PET scan is a sensitive post-therapy surveillance
      modality for detection of recurrent cervical cancer even in asymptomatic patients
      and aids in deciding treatment plans and, eventually, may have favorable impact
      on prognosis and survival.

PMID- 16574206
TI  - The adrenergic alpha2 receptor and sexual incentive motivation in male rats.
AB  - The purpose of the present series of experiments was to determine whether drugs
      acting at the alpha2-adrenoceptor modify unconditioned sexual incentive
      motivation in the male rat. To that end a highly specific agonist,
      dexmedetomidine, a corresponding antagonist, atipamezole, and a less specific
      antagonist, yohimbine, were administered to groups of sexually inexperienced male
      rats. The subjects were tested in a large rectangular arena, where a sexually
      receptive female and an intact male were employed as incentives. The incentive
      animals were confined behind a wire mesh in opposite corners of the arena. The
      animals could see, hear and smell each other, but no sexual interaction was
      possible. Approach to the incentives constituted the measure of incentive
      motivation. In addition, the test provided data on ambulatory activity and
      general arousal. Dexmedetomidine, at a dose of 8 microg/kg, produced a slight
      reduction of sexual incentive motivation. Ambulatory activity and general arousal
      were also inhibited. Atipamezole, in doses of 0.1 and 0.3mg/kg enhanced the
      positive incentive properties of the receptive female. A high dose of 1mg/kg did
      not have any significant effect. Ambulatory activity was slightly reduced by the
      two larger doses of atipamezole. Yohimbine had a slight stimulatory effect on
      sexual incentive motivation at a dose (4 mg/kg) that also reduced ambulatory
      activity and general arousal. It is concluded that blockade of the adrenergic
      alpha2 receptor stimulates sexual incentive motivation in the male rat whereas
      stimulation of it has the opposite effect. At present it is not clear if these
      drug effects are caused by pre- or postsynaptic actions of the drugs, and the
      importance of secondary changes in other neurotransmitter systems remains
      unknown.

PMID- 16574207
TI  - Differences in extinction responding and reinstatement of methamphetamine-seeking
      behavior between Fischer 344 and Lewis rats.
AB  - Fischer 344 (F344) and Lewis (LEW) rats differ in a number of self-administration
      behaviors. Whether or not these strains differ in methamphetamine-primed
      reinstatement of extinguished responding is unknown. F344 and LEW rats were
      trained to self-administer intravenous (i.v.) methamphetamine (0.06 mg/kg) during
      daily 2-h limited access sessions for 14 days. Following methamphetamine self
      administration, subjects underwent a minimum of 6 extinction sessions where
      responding on the previously active lever resulted in no programmed consequences.
      Following extinction sessions, we evaluated strain and dose dependency of
      methamphetamine-primed (0.06, 0.12, or 0.24 mg/kg/i.v.) reinstatement of
      responding. All subjects received each dose once. Dosing order was determined by
      utilizing a within-subjects Latin square design. We found partial strain
      differences in daily methamphetamine self-administration. In addition, F344 rats
      responded significantly more during the first extinction session compared LEW
      rats. Last, the LEW rats demonstrated a heightened propensity to reinstate
      responding following methamphetamine priming injections compared to F344 rats.
      Our results suggest that genetic background influences differences in
      methamphetamine-seeking behaviors in rats.

PMID- 16574208
TI  - Development of a reliable measure of walking within and outside the local
      neighborhood: RESIDE's Neighborhood Physical Activity Questionnaire.
AB  - BACKGROUND: The RESIDential Environment project (RESIDE) is a longitudinal study
      evaluating the impact of a new residential design code on walking. OBJECTIVE: To
      develop a reliable measure of walking--undertaken within and outside the
      neighborhood--and overall physical activity. METHODS: A test-retest reliability
      study was undertaken (n = 82, mean age 39 years). The instrument was based on the
      International Physical Activity Questionnaire (IPAQ-short version) and Active
      Australia Survey. It measured usual frequency and duration of (1) recreational-
      and transport-related walking within and outside the neighborhood and (2) other
      vigorous and moderate physical activities. RESULTS: Reliability of recall of
      whether participants had walked within (k = 0.84) and outside (0.73) the
      neighborhood was acceptable. Similarly, recall of frequency and duration of
      transport and recreational-related walking within the neighborhood was excellent
      (ICC > or = 0.82), as was recall of transport-related walking trips outside the
      neighborhood (ICC > or = 0.84). Reliability for duration of recreational walking
      outside the neighborhood was fair to good (ICC = 0.55). The reliability of
      indices of total physical activity based on MET min/week (ICC = 0.82) and MET
      min/week dichotomized to 'sufficient' physical activity for health (kappa = 0.67)
      were both acceptable. CONCLUSIONS: The Neighborhood Physical Activity
      Questionnaire (NPAQ) is sufficiently reliable for studies examining environmental
      correlates of walking within the neighborhood.

PMID- 16574209
TI  - Holding immature equine oocytes in the absence of meiotic inhibitors: effect on
      germinal vesicle chromatin and blastocyst development after intracytoplasmic
      sperm injection.
AB  - Holding immature oocytes before the onset of maturation simplifies oocyte
      transport and aids in scheduling later manipulations. We report here a method for
      holding equine oocytes in the absence of meiotic inhibitors. In Experiment 1,
      immature oocytes with expanded cumuli were cultured at 38.2 degrees C in medium
      containing cycloheximide, or were held at room-temperature in M199 with Hanks'
      salts, for 16-18 h before maturation. Control oocytes were matured immediately
      after recovery. Oocytes were fertilized by intracytoplasmic sperm injection and
      cultured for 4d. Embryo development was not different among treatments. In
      Experiment 2, oocytes were treated as in Experiment 1, but embryos were cultured
      for 7.5d. Blastocyst development was significantly lower in the cycloheximide
      treated group than in controls (7% versus 30%) with the room-temperature group
      intermediate (16%). In Experiment 3, oocytes were cultured at 38.2 degrees C in
      medium containing roscovitine, or were held at room temperature in sealed glass
      vials in a mixture of 40% M199 with Earle's salts, 40% M199 with Hanks' salts,
      and 20% FBS (EH treatment) for 16-18 h, before maturation, sperm injection, and
      embryo culture for 7.5d. Blastocyst development of oocytes in the EH treatment
      was significantly higher than that for roscovitine-treated oocytes (34% versus
      12%), but not significantly different from that for controls (25%). Oocytes in
      the EH treatment did not mature during holding (70% germinal vesicle stage after
      18 h holding). Whereas culture with cycloheximide or roscovitine of equine
      oocytes with expanded cumuli reduced subsequent blastocyst formation, these
      oocytes could be held in a modified M199 at room temperature overnight without
      adverse affecting meiotic or developmental competence.

PMID- 16574210
TI  - Freezing response and optimal cooling rates for cryopreserving sperm cells of
      striped bass, Morone saxatilis.
AB  - This study explored the optimization of techniques for sperm cryopreservation of
      an economically important fish species, the striped bass Morone saxatilis. The
      volumetric shrinkage or the water transport response during freezing of sperm
      cells was obtained using a differential scanning calorimeter (DSC) technique.
      Water transport was obtained in the presence of extracellular ice at a cooling
      rate of 20 degrees C/min in two different media: (1) without cryoprotective
      agents (CPAs), and (2) with 5% (v/v) dimethyl sulfoxide (DMSO). The sperm cell
      was modeled as a cylinder of length of 22.8 microm and diameter 0.288 microm and
      was assumed to have an osmotically inactive cell volume (V(b)) of 0.6 V(0), where
      V(0) is the isotonic or initial cell volume. By fitting a model of water
      transport to the experimentally determined water transport data, the best fit
      membrane permeability parameters (reference membrane permeability to water, L(pg)
      or L(pg)[cpa] and the activation energy, E(Lp) or E(Lp)[cpa]) were determined and
      ranged from L(pg)=0.011-0.001 microm/min-atm, and E(Lp)=40.2-9.2 kcal/mol). The
      parameters obtained in this study suggested that the optimal rate of cooling for
      striped bass sperm cells in the presence and absence of DMSO range from 14 to 20
      degrees C/min. These theoretically predicted rates of optimally freezing M.
      saxatilis sperm compared quite closely with independent and experimentally
      determined optimal rates of cooling striped bass sperm.

PMID- 16574211
TI  - Changes in serum luteinizing hormone (LH) concentrations in response to
      luteinizing hormone releasing hormone (LHRH) in bull calves that attained puberty
      early or late.
AB  - The objectives of this study were to determine if the response to luteinizing
      hormone releasing hormone (LHRH) could be used to select bull calves capable of
      early sexual maturation and to establish the optimum route and dose of LHRH. In
      Trial 1, at 4, 10 and 20 week of age, 20 calves were treated iv with 2 microg/kg
      body weight of LHRH 1 and 5h after commencing a 9-h period of blood sampling.
      Bulls were separated into early and late maturing (n=10), based on age at puberty
      (scrotal circumference (SC) of >or=28 cm). At 4 and 20 week of age, peak serum LH
      concentrations and area under the LH response curve in response to LHRH were
      lower (P<0.05) in early- versus late-maturing bulls. In Trial 2, calves at 20
      week of age were given LHRH as follows: 2 microg/kg body weight iv (n=6), im
      (n=6) or sc (n=6); 5 microg/kg im (n=6), or ischio-rectally (ir, n=6) or sc
      (n=6); and 10 microg/kg im (n=6) or sc (n=6). Serum LH concentrations were at a
      plateau from 30 to 165 min after treatment with 5 microg/kg of LHRH (im or ir;
      P>0.05). We concluded that the LH responses to LHRH in calves at 4 and 20 week of
      age could facilitate the development of a simple test (one blood sample prior to
      treatment with LHRH and a second during the period of sustained response to LHRH)
      to select early-maturing bulls.

PMID- 16574212
TI  - How to qualify and validate wear simulation devices and methods.
AB  - The clinical significance of increased wear can mainly be attributed to impaired
      aesthetic appearance and/or functional restrictions. Little is known about the
      systemic effects of swallowed or inhaled worn particles that derive from
      restorations. As wear measurements in vivo are complicated and time-consuming,
      wear simulation devices and methods had been developed without, however,
      systematically looking at the factors that influence important wear parameters.
      Wear simulation devices shall simulate processes that occur in the oral cavity
      during mastication, namely force, force profile, contact time, sliding movement,
      clearance of worn material, etc. Different devices that use different force
      actuator principles are available. Those with the highest citation frequency in
      the literature are - in descending order - the Alabama, ACTA, OHSU, Zurich and
      MTS wear simulators. When following the FDA guidelines on good laboratory
      practice (GLP) only the expensive MTS wear simulator is a qualified machine to
      test wear in vitro; the force exerted by the hydraulic actuator is controlled and
      regulated during all movements of the stylus. All the other simulators lack
      control and regulation of force development during dynamic loading of the flat
      specimens. This may be an explanation for the high coefficient of variation of
      the results in some wear simulators (28-40%) and the poor reproducibility of wear
      results if dental databases are searched for wear results of specific dental
      materials (difference of 22-72% for the same material). As most of the machines
      are not qualifiable, wear methods applying the machine may have a sound concept
      but cannot be validated. Only with the MTS method have wear parameters and
      influencing factors been documented and verified. A good compromise with regard
      to costs, practicability and robustness is the Willytec chewing simulator, which
      uses weights as force actuator and step motors for vertical and lateral
      movements. The Ivoclar wear method run on the Willytec machine shows a mean
      coefficient of variation in vertical wear of 12%. Force measurements have
      revealed that in the beginning of the stylus/specimen contact phase the force
      impulse is 3-4 times higher during dynamic loading than during static loading.
      When correlating material properties to the wear results of 23 composite resins
      subjected to the Ivoclar method, some parameters could be identified and
      incorporated into a wear formula to predict wear with the Ivoclar method. A round
      robin test evaluating the wear of ten dental materials with five wear simulation
      methods showed that the results were not comparable, as all methods follow
      different wear testing concepts. All wear methods lack the evidence of their
      clinical relevance because prospective studies correlating in vitro with long
      term in vivo results with identical materials are not available. For direct
      restorative materials, amalgam seems to be a realistic reference material. For
      indirect, namely crown and bridge materials, low strength ceramic is appropriate.

PMID- 16574213
TI  - Comparative biomonitors of coastal trace metal contamination in tropical South
      America (N. Brazil).
AB  - Samples of 5 bivalve molluscs (Crassostrea rhizophorae, Mytella charruana,
      Anomalocardia brasiliana, Anadara ovalis, Phacoides pectinata), 2 barnacles
      (Fistulobalanus citerosum, Balanus amphitrite) and leaves of the mangrove tree
      Rhizophora mangle were collected from up to 11 sites in two estuaries in Natal,
      Brazil--the comparatively contaminated Potengi estuary and the comparatively
      uncontaminated Curimatau estuary. Specimens were analysed for the trace metals
      Zn, Cu, Cd, Fe, Mn and Ni, and a comparative assessment made of the power of the
      different species as trace metal biomonitors. Four of the 5 bivalves (not P.
      pectinata) take up metals from solution and suspended material (food source),
      while P. pectinata as a lucinid with symbiotic chemosynthetic bacteria takes up
      metals from dissolved sources only. The organisms with the strongest net
      accumulation of particular metals showed the greatest discrimination between
      trace metal bioavailabilities between sites. Barnacles (F. citerosum) showed the
      best discrimination, but oysters (C. rhizophorae) are particularly recommended as
      biomonitors given their strong accumulation patterns for many trace metals, their
      large size and their local abundance.

PMID- 16574214
TI  - Comment on equilibrium and kinetics studies of adsorption of copper(II) on
      chitosan and chitosan/PVA beads.

PMID- 16574215
TI  - The roles of C-terminal loop residues of dimeric arginine kinase from sea
      cucumber Stichopus japonicus in catalysis, specificity and structure.
AB  - Arginine kinase (AK) catalyzes the reversible phosphorylation of arginine by
      MgATP to form a high-energy compound phosphoarginine (Parg) and MgADP in forward
      reaction in invertebrates. To detect the different catalytical mechanisms among
      Stichopus-AK (dimer) and Limulus-AK (monomer) and Torpedo creatine kinase
      (dimeric CK) and to reveal the structural role of the C-terminal domain loop (C
      loop) of dimeric AK, six single-site mutants, E314D, E314Q, E314V, F315A, F315H
      and F315Y were constructed as well as two multi-site variants, S312R/F315H/V319E
      (formed by substituting the C-loop of monomeric AK for that of dimeric AK, termed
      the AAloop) and S312G/E314V/F315D/E317A/S318A/G321S (formed by substituting the C
      loop of dimeric CK for that of dimeric AK, termed the ACloop). The AK activity of
      the three mutants at Glu(314) decreased significantly, from 60- to 500-fold. The
      ACloop showed only slight AK activity, unlike the same construction in Limulus
      AK. In addition, all Phe(315) mutants including the AAloop which retained
      Glu(314) had modest AK activity (5-84% of the wild type). All the results above
      suggested that Glu(314) played a more significant role in catalysis in dimeric AK
      than in the monomer. In addition, ANS profiles indicated that the tolerance of
      the three Glu(314) mutants to denaturant decreased slightly compared with wild
      type AK. Though monomeric AK has a His residue at site 315, mutants F315H and the
      AAloop could not resist any perturbation of denaturant, and the mutants showed a
      Gibbs free energy of about 2.7kJ/mol lower than wild type AK. Therefore Phe(315)
      in dimeric AK has a different role from His(315) in monomeric AK. This might
      contribute to the stabilization of the native conformation, while His(315) in
      Limulus AK directly binded to the carboxylate of arginine. Taking all the results
      above together, we suggested a unique mechanism in dimeric AK, different from
      both monomeric AK and dimeric CK.

PMID- 16574216
TI  - Molecularly imprinted polymers for tobacco mosaic virus recognition.
AB  - Molecular imprinted Polymers (MIP) targeted for Tobacco mosaic virus (TMV) have
      been synthesized. Batch equilibrium studies using imprinted and non-imprinted
      polymer hydrogels in TMV and TNV solutions were conducted to determine virus
      binding capacities. TMV-imprinted hydrogels showed increased binding to TMV (8.8
      mg TMV/gpolymer) compared to non-imprinted hydrogels (4.2 mg TMV/gpolymer).
      Furthermore, TMV-imprinted hydrogels exhibited increased binding to TMV compared
      to TNV, while non-imprinted hydrogels bound similar amounts of TMV or TNV. This
      research has demonstrated that molecular imprinting of viruses can be used to
      selectively induce binding of target viruses based on shape differences of their
      virions.

PMID- 16574217
TI  - Fabrication of polymeric microparticles for drug delivery by soft lithography.
AB  - Soft lithographic techniques were used to fabricate polymeric microparticles for
      drug delivery applications. The microparticles were made of thermoplastics and
      thermosets from different types of precursors including reactive resin and
      polymer solutions in organic solvents or water. The microparticles produced using
      these methods were made of widely used polymers for drug delivery with highly
      uniform sizes, plate-like morphology, and well-defined lateral sizes and shapes,
      making them potentially useful for drug delivery applications and as platform for
      the construction of multi-functional drug delivery devices.

PMID- 16574218
TI  - Electrospinning of chitin nanofibers: degradation behavior and cellular response
      to normal human keratinocytes and fibroblasts.
AB  - An electrospinning method was used to fabricate chitin nanofibrous matrices for
      biodegradability and cell behavior tests. The morphology of as-spun chitin
      nanofibers (Chi-N) and commercial chitin microfibers (Beschitin W; Chi-M) was
      investigated by scanning electron microscopy. From the image analysis, the
      average diameters of Chi-N and Chi-M were 163 nm and 8.77 microm, respectively.
      During in vitro degradation for 15 days, the degradation rate of Chi-N was faster
      than that of Chi-M, likely due to higher surface area of Chi-N. Chi-N that was
      grafted into rat subcutaneous tissue had almost degraded within 28 days, and no
      inflammation could be seen on the nanofiber surfaces or in the surrounding
      tissues (except in the early stage wound). To assay and compare the
      cytocompatibility and cell behavior with Chi-N and Chi-M, cell attachment and
      spreading of normal human keratinocytes and fibroblasts seeded on chitin matrices
      and the interaction between cells and chitin fibers were studied. Relatively high
      cell attachment and spreading of all the cells tested were observed on Chi-N in
      comparison to Chi-M, and Chi-N treated with type I collagen significantly
      promoted the cellular response. Our results indicate that the Chi-N, alone or
      with extracellular matrix proteins (particularly type I collagen), could be
      potential candidates for the cell attachment and spreading of normal human
      keratinocytes and fibroblasts. This property of Chi-N might be particularly
      useful for wound healing and regeneration of oral mucosa and skin.

PMID- 16574219
TI  - Biomimetic modification of titanium dental implant model surfaces using the RGDSP
      peptide sequence: a cell morphology study.
AB  - Surface topography and (bio)chemistry are key factors in determining cell
      response to an implant. We investigated cell adhesion and spreading patterns of
      epithelial cells, fibroblasts and osteoblasts on biomimetically modified, smooth
      and rough titanium surfaces. The RGD bioactive peptide sequence was immobilized
      via a non-fouling poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG)
      molecular assembly system, which allowed exploitation of specific cell-peptide
      interactions even in the presence of serum. As control surfaces, bare titanium
      and bio-inactive surfaces (scrambled RDG and unfunctionalized PLL-g-PEG) were
      used. Our findings demonstrated that surface topography and chemistry directly
      influenced the attachment and morphology of all cell types tested. In general, an
      increase in cell number and more spread cells were observed on bioactive
      substrates (containing RGD) compared to bio-inactive surfaces. More fibroblasts
      were present on smooth than on rough topographies, whereas for osteoblasts the
      opposite tendency was observed. Epithelial cell attachment did not follow any
      regular pattern. Footprint areas for all cell types were significantly reduced on
      rough compared to smooth surfaces. Osteoblast attachment and footprint areas
      increased with increasing RGD-peptide surface density. However, no synergy
      (interaction) between RGD-peptide surface density and surface topography was
      observed for osteoblasts neither in terms of attachment nor footprint area.

PMID- 16574220
TI  - The effect of a fibrin-fibronectin/beta-tricalcium phosphate/recombinant human
      bone morphogenetic protein-2 system on bone formation in rat calvarial defects.
AB  - In spite of good prospects for bone morphogenetic proteins (BMP) applications, an
      ideal carrier system for BMPs has not yet been identified. The purpose of this
      study was to evaluate the osteogenic effect of a fibrin-fibronectin sealing
      system (FFSS) combined with beta-tricalcium phosphate (beta-TCP) as a carrier
      system for recombinant human bone morphogenetic proteins (rhBMP-2) in the rat
      calvarial defect model. Eight-millimeter critical-size calvarial defects were
      created in 100 male Sprague-Dawley rats. The animals were divided into five
      groups of 20 animals each. The defects were treated with rhBMP-2/FFSS, rhBMP
      2/FFSS/beta-TCP, FFSS and FFSS/beta-TCP carrier control or were left untreated as
      a sham-surgery control. Defects were evaluated by histologic and histometric
      parameters following a 2- and 8-week healing interval (10 animals/group/healing
      intervals). The FFSS/beta-TCP carrier group was significantly greater in new bone
      area at 2 weeks (p<0.05) and new tissue area at 2 and 8 weeks (p<0.01) relative
      to the FFSS carrier group. New bone and new tissue area in the rhBMP-2/FFSS/beta
      TCP group were significantly greater than in the rhBMP-2/FFSS group at 8 weeks
      (p<0.01). On histologic observation, FFSS remnants were observed at 2 weeks, but
      by 8 weeks, the FFSS appeared to be completely resorbed. rhBMP-2 combined with
      FFSS/beta-TCP produced significantly more new bone and new tissue formation in
      this calvarial defect model. In conclusion, FFSS/beta-TCP may be considered as an
      available carrier for rhBMP-2.

PMID- 16574221
TI  - The integrity of welded interfaces in ultra-high molecular weight polyethylene:
      Part 2--interface toughness.
AB  - In Part 2 of a study of welding of ultra-high molecular weight polyethylene
      (UHMWPE), experiments were conducted to measure the interfacial fracture energy
      of butt welds, for various welding times and temperatures above the melting
      point. Their toughness was investigated at 37 degrees C in terms of their
      fracture energy, obtained by adapting the essential work of fracture (EWF)
      method. However, a proportion of the welded samples (generally decreasing with
      increasing welding time or temperature) failed in dual ductile/brittle mode,
      hence invalidating the EWF test. Even those failing in purely ductile mode showed
      a measurable interface work of fracture only for the highest weld temperature and
      time: 188 degrees C and 90 min. Results from the model presented in Part 1 show
      that this corresponds to the maximum reptated molecular weight reaching close to
      the peak in the molar mass distribution. Hence this work provides the first
      experimental evidence that the slow rate of self-diffusion in UHMWPE leads to
      welded interfaces acting as low-toughness crack paths. Since such interfaces
      exist around every powder particle in processed UHMWPE this problem cannot be
      avoided, and it must be accommodated in design of hip and knee bearing surfaces
      made from this polymer.

PMID- 16574222
TI  - Biocompatibility of alginate-poly-L-lysine microcapsules for cell therapy.
AB  - Cell microencapsulation holds promise for the treatment of many diseases by the
      continuous delivery of therapeutic products. The biocompatibility of the
      microcapsules and their biomaterials components is a critical issue for the long
      term efficacy of this technology. The objective of this paper is to provide
      detailed information about the principal factors affecting the biocompatibility
      of alginates and alginate-poly-l-lysine microcapsules, which are the most
      frequently employed biomaterials and encapsulation devices for cell
      immobilization, respectively. Some of these factors include the alginate
      composition and purification, the selection of the polycation, the interactions
      between the alginates and the polycation, the microcapsule fabrication process,
      the uniformity of the devices and the implantation procedure. Improved knowledge
      will lead to the production of standardized transplantation-grade biomaterials
      and biocompatible microcapsules.

PMID- 16574223
TI  - A hypothetical mechanism of bone remodeling and modeling under electromagnetic
      loads.
AB  - A hypothetical regulation mechanism for bone modeling and remodeling under
      electromagnetic field is proposed. In this hypothesis, the bone modeling and
      remodeling mechanism is described as follows: the circular loads that we bear
      during ordinary daily activities generate micro-damage in cortical bone and these
      micro-cracks are removed by osteoclasts. Then growth factors, which are in latent
      forms in osteocytes, are activated by osteoclasts and released into bone fluid.
      These growth factors stimulate osteoblasts to refill the cavities. An
      electromagnetic field can stimulate the multiplication of growth factors and
      accelerate the bone remodeling process indirectly. It can be seen that many
      features reported in adaptive bone modeling and remodeling are explained by the
      proposed hypothesis. Further, a computational model is established based on the
      hypothesis, which can simulate the bone modeling and remodeling process under
      multi-field loads.

PMID- 16574224
TI  - Carcinoembryonic antigen and related molecules in normal and transformed
      trophoblast.
AB  - Carcinoembryonic antigen (CEA, CD66e) and CEA-related cell adhesion molecules
      (CEACAMs) are important mediators in remodeling of diverse human tissues, and
      modulators of cell proliferation and differentiation. Expression by normal and
      transformed trophoblast of gestational trophoblastic diseases (GTDs), isolated
      cytotrophoblast and choriocarcinoma cell lines is presented here.
      Immunocyto/histochemistry of normal placenta (n=9), invasive mole (n=8),
      choriocarcinoma (n=7), a placental site trophoblastic tumor, cytotrophoblast in
      primary culture and JAr and JEG-3 cells was performed using polyclonal anti-CEA
      and specific monoclonal anti-CEA antibodies. Data were analyzed and scored using
      Mann-Whitney Test. CEA and CEA-related molecules were identified by Western blot
      and immunoaffinity chromatography in JAr and JEG-3 cells and extracts of 1st and
      3rd trimester of pregnancy tissue and cytotrophoblast cell lysates. CEA is
      expressed throughout pregnancy, in first trimester predominantly in
      syncytiotrophoblast, but also in villous cytotrophoblast and extravillous
      trophoblast. Data presented here demonstrate that CEA is significantly increased
      in transformed trophoblast of GTDs (p<0.05). Both cytotrophoblast in primary
      culture and choriocarcinoma cell lines express CEA, with staining of granular
      deposits in JAr and cell membrane in JEG-3. The results suggest that CEA (CD66e)
      and other CEA-related protein(s) could be involved in trophoblast
      differentiation.

PMID- 16574225
TI  - A phase II study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating
      agent, in patients with very high risk relapsed acute myeloid leukemia.
AB  - Cloretazine (VNP40101M) is a sulfonylhydrazine alkylating agent with significant
      anti-leukemia activity. A multicenter phase II study of cloretazine was conducted
      in patients with first relapse of acute myeloid leukemia (AML) following an
      initial complete remission (CR) of less than 12 months. Cloretazine was given as
      a single intravenous infusion at a dose of 600 mg/m(2). Fifty-three patients
      (median age 62 years (18-84), 41 of 44 (93%) evaluable with intermediate or high
      risk cytogenetics, 32 (60%) with initial CR durations < or =6 months) were
      treated on study. Two patients (4%) achieved a second CR. Five (9%) patients died
      within 30 days of receiving cloretazine therapy. Median overall survival (2.3
      months) in the study cohort was directly comparable to that of 233 matched
      patients treated with other single agents. The study cloretazine regimen had
      minimal activity in a very high risk subset of patients with relapsed AML.

PMID- 16574226
TI  - Cannabinoids and prefrontal cortical function: insights from preclinical studies.
AB  - Marijuana use has been associated with disordered cognition across several
      domains influenced by the prefrontal cortex (PFC). Here, we review the
      contribution of preclinical research to understanding the effects of cannabinoids
      on cognitive ability, and the mechanisms by which cannabinoids may affect the
      neurochemical processes in the PFC that are associated with these impairments. In
      rodents, acute administration of cannabinoid agonists produces deficits in
      working memory, attentional function and reversal learning. These effects appear
      to be largely dependent on CB1 cannabinoid receptor activation. Preclinical
      studies also indicate that the endogenous cannabinoid system may tonically
      regulate some mnemonic processes. Effects of cannabinoids on cognition may be
      mediated via interaction with neurochemical processes in the PFC and hippocampus.
      In the PFC, cannabinoids may alter dopaminergic, cholinergic and serotonergic
      transmission. These mechanisms may underlie cognitive impairments observed
      following marijuana intake in humans, and may also be relevant to other disorders
      of cognition. Preclinical research will further enhance our understanding of the
      interactions between the cannabinoid system and cognitive functioning.

PMID- 16574227
TI  - Somatic mutations and activation-induced cytidine deaminase (AID) expression in
      established rheumatoid factor-producing lymphoblastoid cell line.
AB  - Epstein-Barr virus (EBV) transforms human peripheral B cells into lymphoblastoid
      cell lines (LCLs), allowing the production of specific antibody-secreting cell
      lines. We and others have previously found that in contrast to peripheral blood B
      cells, EBV-transformed lymphoblastoid cell lines express the activation-induced
      cytidine deaminase (AID) gene. The opposite is true for the germinal center
      specific BCL6 gene: it is expressed in adult peripheral blood B cells and is no
      longer expressed in LCLs. The present work extends our findings and shows that
      whereas AID expression is rapidly induced following EBV infection, BCL6
      expression is gradually down-regulated and is fully extinguished in already
      established LCLs. The question of whether AID activation induces the process of
      somatic hypermutation (SHM) was investigated in adult-derived LCLs. It was found
      that the VH gene from the rheumatoid factor-producing RF LCL (derived from a
      rheumatoid arthritis patient), accumulated somatic point mutations in culture.
      Overall, nine unique mutations have accumulated in the rearranged VH gene since
      the generation of the RF cell line. Four additional intraclonal mutations were
      found among 10 cellular clones of the RF cells. One out of the four was in CDR1
      and could be correlated with loss of antigen-binding activity in three out of the
      10 clones. Altogether, these 13 mutations were preferentially targeted to the
      DGYW motifs and showed preference for CG nucleotides, indicating that they were
      AID-mediated. By contrast, mutations were not detected among 3700-4000
      nucleotides each of the Vlambda, Cmu and GAPDH genes derived from the same RF
      cell cultures and the cellular clones. Our results thus show that AID may
      generate point mutations in the rearranged Ig VH during in vitro cell culture of
      adult-LCLs and that these mutations may be responsible, at least in part, for the
      known instability and occasional loss of antigen-binding activity of antibody
      secreting LCLs.

PMID- 16574228
TI  - GCSF receptor regulates antigen uptake and expression of cytokines and
      costimulatory molecules in dendritic cells.
AB  - RNA interference (RNAi), a process that specifically silences target gene
      expression, is a powerful technique to modulate cellular functions. In this
      study, we identified two small interference RNA (siRNA) sequences that can
      specifically and efficiently silence the expression of the granulocyte colony
      stimulating factor receptor (GCSF-R) gene and achieved stable knockdown of GCSF-R
      using pFIV lentivirus containing the GCSF-R siRNA. GCSF-R knockdown significantly
      reduces the expression of IL-lalpha, IL-lbeta, IL-6, IL-10, H-2Kb, I-Ab, CD80 and
      CD86, and increases PDL1 and PDL2 expression, while IL-12p35, TGFbeta, TNFalpha
      and CD40 expression is unaltered. Furthermore, GCSF-R knockdown significantly
      changes the endocytosis and micro-pinocytosis abilities as well as surface
      expression of antigens of DC2.4 cells.

PMID- 16574229
TI  - Hand tremor related to smoking habits and the consumption of caffeine in male
      industrial workers.
AB  - Tremor was measured in 49 smokers/snuffers and in 49 non-smokers/non-snuffers in
      a cross-sectional study. The Klove-Matthews static steadiness test and TREMOR 7.0
      from the CATSYS test system were used to assess the hand tremor. The creatinine
      (cr) corrected arithmetic mean concentrations of cotinine in urine were 11
      microg/g cr (range 0.1-430) in the non-smokers/non-snuffers compared to 1,417
      microg/g cr (range 45-3,780) in the smokers/snuffers. The geometric mean urinary
      caffeine concentrations were 797 microg/g cr (range 0.5-13,330) in the non
      smokers/non-snuffers versus 654 microg/g cr (range 0.9-7,470) in the
      smokers/snuffers. Increased tremor was found in the group of smokers/snuffers
      compared to the non-smokers/non-snuffers for several parameters on the tremor
      measurements, e.g. geometric mean tremor intensity of 0.14 m/s(2) (range 0.09
      0.40) in the smokers/snuffers versus 0.11 m/s(2) (range 0.07-0.22) in the non
      smokers/non-snuffers for the dominant hand were quantified. Also the mean scores
      on the static steadiness test were inferior in the smokers/snuffers, in
      particular for the number of touches. The results further indicate that the
      frequency dispersion is smaller in the smokers/snuffers compared to the non
      smokers/non-snuffers. No systematic association was observed between the
      biomarkers of nicotine and caffeine exposure and the tremor measurements.
      However, older age appeared to be an important predictor for the magnitude of
      tremor in the smokers/snuffers, but not in the non-smokers/non-snuffers.

PMID- 16574230
TI  - Identification of Trp106 as the tryptophanyl radical intermediate in
      Synechocystis PCC6803 catalase-peroxidase by multifrequency Electron Paramagnetic
      Resonance spectroscopy.
AB  - The reactive intermediates formed in the catalase-peroxidase from Synechocystis
      PCC6803 upon reaction with peroxyacetic acid, and in the absence of peroxidase
      substrates, are the oxoferryl-porphyrin radical and two subsequent protein-based
      radicals that we have previously assigned to a tyrosyl (Tyr()) and tryptophanyl
      (Trp()) radicals by using multifrequency Electron Paramagnetic Resonance (EPR)
      spectroscopy combined with deuterium labeling and site-directed mutagenesis. In
      this work, we have further investigated the Trp() in order to identify the site
      for the tryptophanyl radical formation, among the 26 Trp residues of the enzyme
      and to possibly understand the protein constraints that determine the selective
      formation of this radical. Based on our previous findings about the absence of
      the Trp() intermediate in four of the Synechocystis catalase-peroxidase variants
      on the heme distal side (W122F, W106A, H123Q, and R119A) we constructed new
      variants on Trp122 and Trp106 positions. Trp122 is very close to the iron on the
      heme distal side while Trp106 belongs to a short stretch (11 amino acid residues
      on the enzyme surface) that is highly conserved in catalase-peroxidases. We have
      used EPR spectroscopy to characterize the changes on the heme microenvironment
      induced by these mutations as well as the chemical nature of the radicals formed
      in each variant. Our findings identify Trp106 as the tryptophanyl radical site in
      Synechocystis catalase-peroxidase. The W122H and W106Y variants were specially
      designed to mimic the hydrogen-bond interactions of the naturally occurring Trp
      residues. These variants clearly demonstrated the important role of the extensive
      hydrogen-bonding network of the heme distal side, in the formation of the
      tryptophanyl radical. Moreover, the fact that W106Y is the only Synechocystis
      catalase-peroxidase variant of the distal heme side that recovers a catalase
      activity comparable to the WT enzyme, strongly indicates that the integrity of
      the extensive hydrogen-bonding network is also essential for the catalatic
      activity of the enzyme.

PMID- 16574231
TI  - Gender and genetic background effects on brain metal levels in APP transgenic and
      normal mice: implications for Alzheimer beta-amyloid pathology.
AB  - The incidence of Alzheimer's disease (AD) is greater in women than men at any
      age, as is the development of amyloid pathology in several transgenic mouse
      models of AD. Due to the involvement of metals in AD pathogenesis, variations
      between the sexes in metal metabolism may contribute to the sex difference in AD
      risk. In this study, we investigated sex differences in brain metal levels across
      the lifespan in mice of two different background strains, as well as in mice
      overexpressing the human amyloid precursor protein (APP) and amyloid-beta protein
      (Abeta). We demonstrate consistently lower Cu and higher Mn levels in females
      compared with males at any age studied. The sex differences in Cu and Mn levels
      are independent of APP/Abeta expression. AD brain exhibits decreased Cu and
      increased Mn levels, as do transgenic mice overexpressing APP or Abeta. The age
      dependent elevations of Cu, Fe and Co levels were found to be significantly
      greater in mice of B6/SJL background compared with B6/DBA. If depleting Cu and/or
      rising Mn levels contribute to AD pathogenesis, natural sex differences in these
      brain metal levels may contribute to the increased propensity of females to
      develop AD.

PMID- 16574232
TI  - Consistent simulation of X- and Q-band EPR spectra of an unsymmetric dinuclear
      Mn2(II,III) complex.
AB  - Simulation of X- and Q-band electron paramagnetic resonance (EPR) spectra of an
      unsymmetric dinuclear [Mn(2)(II,III)L(mu-OAc)(2)]ClO(4) complex (1), (L is the
      dianion of 2-{[N,N-bis(2-pyridylmethyl)amino]methyl}-6-{[N-(3,5-di-tert-butyl-2
      hydroxybenzyl)-N-(2-pyridylmethyl)amino]methyl}-4-methylphenol) was performed
      using one consistent set of simulation parameters. Rhombic g-tensors and
      hyperfine tensors were necessary to obtain satisfactory simulation of the EPR
      spectra. The anisotropy of the effective hyperfine tensors of each individual
      (55)Mn ion was further analyzed in terms of intrinsic hyperfine tensors. Detailed
      analysis shows that the hyperfine anisotropy of the Mn(III) ion is a result of
      the Jahn-Teller effect and thus an inherent character. In contrast, the anomalous
      hyperfine anisotropy of the Mn(II) ion is attributed as being transferred from
      the Mn(III) ion through the spin exchange interaction. The anisotropy parameter
      for the Mn(II) is deduced as D(II)=-1.26+/-0.2cm(-1). This is the first reported
      D(II) value for a Mn(II) ion in a weakly exchange coupled mixed-valence
      Mn(2)(II,III) complex with a bis-mu-acetato-bridge. The [see text] electronic
      configuration of the Mn(III) ion in 1 is revealed by the negative sign of its
      intrinsic hyperfine tensor anisotropy, Deltaa(III)=a(z)-a(x,y)=-46cm(-1). Lower
      spectral resolution of the Q-band EPR spectrum as compared to the X-band EPR
      spectrum is associated to large line width broadening of the x- and y-components
      in contrast to the z-component. The origins of the unequal distribution of line
      width between the z- and x-, y-components are discussed.

PMID- 16574233
TI  - Regulation of metabotropic glutamate receptor signaling, desensitization and
      endocytosis.
AB  - Metabotropic glutamate receptors (mGluRs) comprise a unique family of G protein
      coupled receptors (GPCR) that can be classified into 3 groups based on G protein
      coupling specificity and sequence similarity. Group I mGluRs (mGluR1 and mGluR5)
      are coupled to the heterotrimeric G protein Galpha(q/11) and trigger the release
      of calcium from intracellular stores. In the present review, we discuss the
      molecular mechanisms involved in the desensitization and endocytosis of group I
      mGluRs. Group I mGluRs desensitize in response to both second-messenger-dependent
      protein kinases and G protein-coupled receptor kinases (GRK). However, GRK2
      mediated mGluR1 desensitization appears to be both phosphorylation- and beta
      arrestin-independent. In addition to GRK-mediated uncoupling of mGluRs from
      heterotrimeric G proteins, the huntingtin-interacting protein, optineurin, also
      contributes to mGluR1 and mGluR5 desensitization. The G protein-uncoupling
      activity of optineurin appears to be facilitated by the presence of polyglutamine
      expanded mutant huntingtin but not wild-type huntingtin. Group I mGluRs also
      undergo both agonist-dependent and -independent endocytosis in both heterologous
      cell expression systems and primary neuronal cultures. The present review
      overviews the current understanding of the contribution of second messenger
      dependent protein kinases, beta-arrestins and a novel Ral/phospholipase D2 (PLD2)
      mediated endocytic pathway to the regulation of Group I mGluR endocytosis.
      Overall, the regulation of Group I mGluR desensitization and endocytosis appears
      to be mediated by the same molecular intermediates as have been described for
      more typical GPCR such as the beta(2)-adrenergic receptor. However, there appears
      to be subtle, but important, differences in the mechanisms by which these
      intermediates are employed to regulate Group I mGluR desensitization and
      endocytosis.

PMID- 16574234
TI  - Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary
      heart disease.
AB  - Innovative pharmacological approaches to raise anti-atherogenic high-density
      lipoprotein-cholesterol (HDL-C) are currently of considerable interest,
      particularly in atherogenic dyslipidemias characterized by low levels of HDL-C,
      such as type 2 diabetes, the metabolic syndrome, and mixed dyslipidemia, but
      equally among individuals with or at elevated risk for premature cardiovascular
      disease (CVD). Epidemiological and observational studies first demonstrated that
      HDL-C was a strong, independent predictor of coronary heart disease (CHD) risk,
      and suggested that raising HDL-C levels might afford clinical benefit.
      Accumulating data from clinical trials of pharmacological agents that raise HDL-C
      levels have supported this concept. In addition to the pivotal role that HDL-C
      plays in reverse cholesterol transport and cellular cholesterol efflux, HDL
      particles possess a spectrum of anti-inflammatory, anti-oxidative, anti
      apoptotic, anti-thrombotic, vasodilatory and anti-infectious properties, all of
      which potentially contribute to their atheroprotective nature. Significantly,
      anti-atherogenic properties of HDL particles are attenuated in common metabolic
      diseases that are characterized by subnormal HDL-C levels, such as type 2
      diabetes and metabolic syndrome. Inhibition of cholesteryl ester transfer protein
      (CETP), a key player in cholesterol metabolism and transport, constitutes an
      innovative target for HDL-C raising. In lipid efficacy trials, 2 CETP inhibitors
      JTT-705 and torcetrapib-induced marked elevation in HDL-C levels, with
      torcetrapib displaying greater efficacy. Moreover, both agents attenuate aortic
      atherosclerosis in cholesterol-fed rabbits. Clinical trial data demonstrating the
      clinical benefits of these drugs on atherosclerosis and CHD are eagerly awaited.

PMID- 16574235
TI  - The human reelin gene: transcription factors (+), repressors (-) and the
      methylation switch (+/-) in schizophrenia.
AB  - A recent report suggests that the down-regulation of reelin and glutamic acid
      decarboxylase (GAD(67)) mRNAs represents 2 of the more consistent findings thus
      far described in post-mortem material from schizophrenia (SZ) patients [reviewed
      in. Neurochemical markers for schizophrenia, bipolar disorder amd major
      depression in postmortem brains. Biol Psychiatry 57, 252-260]. To study
      mechanisms responsible for this down-regulation, we have analyzed the promoter of
      the human reelin gene. Collectively, our studies suggest that SZ is characterized
      by a gamma-amino butyric acid (GABA)-ergic neuron pathology presumably mediated
      by promoter hypermethylation facilitated by the over-expression of the
      methylating enzyme DNA methyltransferase (Dnmt) 1. Using transient expression
      assays, promoter deletions and co-transfection assays with various transcription
      factors, we have shown a clear synergistic action that is a critical component of
      the mechanism of the trans-activation process. Equally important is the
      observation that the reelin promoter is more heavily methylated in brain regions
      in patients diagnosed with SZ as compared to non-psychiatric control subjects
      [Grayson, D. R., Jia, X., Chen, Y., Sharma, R. P., Mitchell, C. P., & Guidotti,
      A., et al. (2005). Reelin promoter hypermethylation in schizophrenia. Proc Natl
      Acad Sci U S A 102, 9341-9346]. The combination of studies in cell lines and in
      animal models of SZ, coupled with data obtained from post-mortem human material
      provides compelling evidence that aberrant methylation may be part of a core
      dysfunction in this psychiatric disease. More interestingly, the hypermethylation
      concept provides a coherent mechanism that establishes a plausible link between
      the epigenetic misregulation of multiple genes that are affected in SZ and that
      collectively contribute to the associated symptomatology.

PMID- 16574236
TI  - Cholesterol and the interaction of proteins with membrane domains.
AB  - Cholesterol is not uniformly distributed in biological membranes. One of the
      factors influencing the formation of cholesterol-rich domains in membranes is the
      unequal lateral distribution of proteins in membranes. Certain proteins are found
      in cholesterol-rich domains. In some of these cases, it is as a consequence of
      the proteins interacting directly with cholesterol. There are several structural
      features of a protein that result in the protein preferentially associating with
      cholesterol-rich domains. One of the best documented of these is certain types of
      lipidations. In addition, however, there are segments of a protein that can
      preferentially sequester cholesterol. We discuss two examples of these
      cholesterol-recognition elements: the cholesterol recognition/interaction amino
      acid consensus (CRAC) domain and the sterol-sensing domain (SSD). The
      requirements for a CRAC motif are quite flexible and predict that a large number
      of sequences could recognize cholesterol. There are, however, certain proteins
      that are known to interact with cholesterol-rich domains of cell membranes that
      have CRAC motifs, and synthetic peptides corresponding to these segments also
      promote the formation of cholesterol-rich domains. Modeling studies have provided
      a rationale for certain requirements of the CRAC motif. The SSD is a larger
      protein segment comprising five transmembrane domains. The amino acid sequence
      YIYF is found in several SSD and in certain other proteins for which there is
      evidence that they interact with cholesterol-rich domains. The CRAC sequences as
      well as YIYF are generally found adjacent to a transmembrane helical segment.
      These regions appear to have a strong influence of the localization of certain
      proteins into domains in biological membranes. In addition to the SSD, there is
      also a domain found in soluble proteins, the START domain, that binds lipids.
      Certain proteins with START domains specifically bind cholesterol and are
      believed to function in intracellular cholesterol transport. One of these
      proteins is StAR-D1, that also has a mitochondrial targeting sequence and plays
      an important role in delivering cholesterol to the mitochondria of steroidogenic
      cells.

PMID- 16574237
TI  - Signaling functions of phosphatidic acid.
AB  - Phosphatidic acid (PA) has emerged as a new class of lipid mediators involved in
      diverse cellular functions in plants, animals, and microorganisms. Considerable
      progress has been made recently on the production, cellular function, and mode of
      action of PA in the cell. The cellular levels of PA undergo dynamic changes in
      response to developmental and environmental stimuli. The production of signaling
      PA is mediated by families of multiple enzymes that regulate the timing,
      location, amount, and molecular species of PA. A number of PA target proteins
      have been identified, which include proteins involved in phosphorylation and
      dephosphorylation of proteins and lipids, as well as in G protein regulation,
      vesicular trafficking, and metabolism. PA mediates cellular functions through
      different modes of action, such as membrane tethering, modulation of enzymatic
      activities, and/or structural effects on cell membranes. The regulatory processes
      in which PA has been implicated include signaling pathways in cell growth,
      proliferation, reproduction, and responses to hormones and biotic and abiotic
      stresses.

PMID- 16574238
TI  - A novel method for evaluating free radical scavenging abilities of antioxidants
      using ultraviolet induction of bacteriophage lambda.
AB  - A novel biological method used to evaluate free radical scavenging abilities of
      antioxidants using ultraviolet (UV) induction of bacteriophage lambda in
      lysogenic Escherichia coli kappa12 (lambda+) has been developed. This method is
      based on the induction of bacteriophage lambda from lysogenic cycle to lytic
      cycle by ultraviolet irradiation, and formation of free radicals during the
      course of induction. In the experiments, 10(8)cells/ml and 30s (39J/m2) were
      determined as the cell density of the lysogenic bacterium and UV irradiation
      time, respectively. The reliability of this method was demonstrated by electron
      paramagnetic resonance (EPR) spectroscopy and spin trapping with DMPO. This
      method had good reproducibility with intra-day variations (RSD, %) of less than
      4% and inter-day variations (RSD, %) of less than 5%, respectively. By this
      method, the free radical scavenging abilities (ID50) of well-known antioxidants
      such as glutathione, superoxide dismutase (SOD), catalase (CAT) and carotenoids
      were determined quantitatively. The results were consistent with the ones
      obtained by conventional methods for evaluating free radical scavenging
      abilities. This developed method is reliable and uses common instruments and
      inexpensive, stable reagents, thus it could be utilized as a routine laboratory
      quantitative assay to screen a large number of substances that have potential to
      scavenge the free radical.

PMID- 16574239
TI  - Chromatin immunoprecipitation in postmortem brain.
AB  - Methylation and other covalent modifications of nucleosome core histones are key
      regulators of chromatin structure and function, including epigenetic control of
      gene expression. For the human brain, however, very little is known about the
      regulation of histone modifications at specific genomic loci. Furthermore,
      chromatin immunoprecipitation protocols applicable to postmortem tissue are
      lacking, and the impact of potential confounds such as autolysis time or tissue
      pH is unknown. We treated cerebral cortex from human postmortem brain and mice by
      micrococcal nuclease digestion or, alternatively, by formaldehyde-crosslinking
      and sonication. We show that the bulk of nucleosomal DNA remains attached to
      histones during the first 30 h after death. Immunoprecipitation with antibodies
      against methylated histones was at least 10-fold more effective in unfixed,
      micrococcal nuclease-digested samples, in comparison to extracts prepared by
      fixation and sonication. Histone methylation differences across various genomic
      sites were maintained within a wide range of autolysis times and tissue pH.
      Therefore, immunoprecipitation of micrococcal nuclease-digested tissue extracts
      is a feasible approach to profile histone methylation at defined genomic loci in
      postmortem brain.

PMID- 16574240
TI  - Measurement of phase gradients in the EEG.
AB  - Previous research has shown that spatio-temporal waves in the EEG are generally
      of long spatial wavelength and form smooth patterns of phase gradients at
      particular time-samples. This paper describes a method to measure smooth phase
      gradients of long spatial wavelength in the EEG. The method depends on the global
      pattern of phase at a given frequency and time and is therefore robust to
      variations, over time, in phase-lag between particular sites. Phases were
      estimated in the EEG signal using wavelet or short time-series Fourier methods.
      During an auditory oddball task, phases across the scalp tend to fall within a
      limited circular range, a range that is not indicative of phase-synchrony nor
      waves with multiple periods. At times the phases tended to maintain a spatially
      and temporally ordered relationship. The relative phases were analysed using
      three phase gradient basis functions, providing a measure of the amount of
      variance explained, across the electrodes, by smooth changes in relative phase
      from a single minimum or single maximum. The data from 586 adult subjects were
      analysed and it was found that the probability of phase gradient events varies
      with time and frequency in the stimulus-locked average, and with task demands.
      The temporal extent of spatio-temporal waves was measured by detecting smoothly
      changing patterns of phase latencies across the scalp. The specific spatial
      pattern and timing of phase gradients correspond closely to the latency
      distributions of certain ERPs.

PMID- 16574241
TI  - An intact peripheral nerve preparation for monitoring the activity of single,
      periosteal afferent nerve fibres.
AB  - A preparation is described in which it is possible to selectively activate and
      monitor the activity of the individual periosteal afferent nerve fibres arising
      from the humerus bone of the cat. The nerve is a fine branch of the median nerve
      that accompanies the small artery and vein that enter the nutrient foramen of the
      humerus. By freeing this fine nerve from nearby tissue over a length of
      approximately 1-2 cm and placing it over a silver hook recording electrode, it
      becomes possible to identify and monitor electrophysiologically, the impulse
      activity of individual periosteal afferent fibres activated by focal mechanical
      stimulation of the periosteum. With this preparation it will be possible to
      examine the central actions and security of transmission at central synaptic
      targets for single, small-diameter afferent fibres arising from bone.

PMID- 16574242
TI  - In vitro sacral cord preparation and motoneuron recording from adult mice.
AB  - We report the development of an intracellular recording technique for adult mouse
      motoneurons in sacral spinal cord. Based on a similar preparation for adult rat,
      we modified the cord preparation solution and filled the sharp electrode with a
      solution that has physiological osmolarity and pH. The viability of the
      preparation was examined by recording root reflexes. Short-latency reflexes
      mediated through monosynaptic transmission between S1 and S3 ventral root were
      reliably produced by dorsal root electrical stimuli and were stably recorded for
      more than eight hours. Long-lasting potentiation of the root reflex was observed
      by bath application of methoxamine, a noradrenergic alpha1 receptor agonist. Bath
      application of strychnine and picrotoxin, antagonists for glycine and GABA(A)
      receptors respectively, unmasked long-lasting reflexes that may contain
      polysynaptic components. In addition, on the background of strychnine and
      picrotoxin, adding methoxamine induced spontaneous ventral root activity. For
      intracellular recording, the motoneurons could be reliably penetrated and held
      for up to 30 min. In all 16 motoneurons recorded, resting membrane potential,
      input resistance, action potentials and repetitive firing were comparable to
      those of rat motoneurons. Thus, this preparation is viable and provides a new
      method for combined electrophysiological and genetic studies of the adult mouse
      spinal cord.

PMID- 16574243
TI  - Characterization of hind paw licking and lifting to noxious radiant heat in the
      rat with and without chronic inflammation.
AB  - The paw withdrawal latency to thermal radiant heat stimuli is a widely used
      nociceptive measure to study hyperalgesic mechanisms. In the present study, in
      addition to the paw withdrawal latency, two behavioral components of pain
      behaviors, paw licking and paw lifting have been characterized and quantified.
      The thermal stimuli were successively applied to the plantar surface of the rat
      hind paws and recorded the behavioral responses to each of the stimuli. Noxious
      radiant heat significantly increased the frequency of paw lifting behavior in
      naive rats. On the other hand, the thermal stimuli significantly evoked the
      occurrence of paw licking behavior in inflamed paws and it was maintained at all
      time points of measurements. The paw withdrawal latency decreased in inflamed
      rats in comparison with control rats. These data informs that noxious radiant
      heat specifically evokes the frequency of paw lifting behavior in normal
      physiological condition, and paw licking behavior in a pathological inflammatory
      condition. These findings suggest that in addition to the measurement of PWL,
      scoring of paw licking and lifting behaviors will improve the sensitivity of this
      pain test.

PMID- 16574244
TI  - Sexual dimorphism in expression of receptors for bacterial lipopolysaccharides in
      murine macrophages: a possible mechanism for gender-based differences in
      endotoxic shock susceptibility.
AB  - Gender-based differences in the incidence and severity of bacterial sepsis render
      males more susceptible to septic shock than females. However, the mechanisms that
      underlie this sexual dimorphism remain unclear. In the present study we confirm
      that males produce significantly higher levels of the inflammatory cytokine IL-6
      and the acute phase protein LPS-binding protein (LBP) than females following in
      vivo lipopolysaccharide (LPS) exposure. It has also been verified that LPS
      challenged male-derived macrophages produce higher levels of IL-1beta and lower
      levels of PGE(2) than similarly treated female-derived cells. Importantly, we
      demonstrated that male-derived macrophages produce significantly higher levels of
      the inflammatory chemokine IP-10 following LPS challenge than their female
      counterparts. It has been demonstrated further that, although resting macrophage
      levels of mRNA encoding Toll-like receptor 4 (TLR4) and its co-receptor CD14, are
      not significantly different between genders, male-derived macrophages
      constitutively express higher levels of these proteins on their cell surface.
      Elevated circulating levels of LBP and constitutively higher cell surface
      expression of TLR4 and CD14 on macrophages in males could result in the observed
      sexual dimorphism in LPS-induced inflammatory mediator production and the greater
      susceptibility of males to bacterial sepsis.

PMID- 16574245
TI  - Production of monoclonal antibodies specific for native equine IgE and their
      application to monitor total serum IgE responses in Icelandic and non-Icelandic
      horses with insect bite dermal hypersensitivity.
AB  - Immunoglobulin E forms a minor component of serum antibody in mammals. In tissues
      IgE is bound by FcvarepsilonRI receptors on the surface of mast cells and
      mediates their release of inflammatory substances in response to antigen. IgE and
      mast cells have a central role in immunity to parasites and the pathogenesis of
      allergic diseases in horses and other mammals. This paper describes the
      production of several novel monoclonal antibodies that detect native equine IgE
      in immunohistology, ELISA and Western blotting. An antigen capture ELISA to
      quantify equine IgE in serum has been developed using two of these antibodies.
      The mean serum IgE concentration of a group of 122 adult horses was 23,523ng/ml
      with a range of 425-82,610ng/ml. Total serum IgE of healthy horses was compared
      with that of horses with insect bite dermal hypersensitivity (IBDH) an allergic
      reaction to the bites of blood feeding insects of Culicoides or Simulium spp.
      IBDH does not occur in Iceland where Culicoides spp. are absent, but following
      importation into mainland Europe native Icelandic horses have an exceptionally
      high incidence of this condition. In the present study Icelandic horses with IBDH
      had significantly higher total IgE than healthy Icelandic horse controls
      (P<0.05). By contrast in horses of other breeds the difference in total serum IgE
      between those affected with IBDH and healthy controls was not statistically
      significant. Total serum IgE was also monitored in a cohort of Icelandic horses
      prior to import into Switzerland and for a period of 3 years thereafter. High
      levels of serum IgE were present in all horses at the start of the study but
      dropped in the first year after import. Thereafter the total serum IgE remained
      low in Icelandic horses that remained healthy but rose significantly (P<0.05) in
      those that developed IBDH. These results support the conclusion that IBDH is a
      type I hypersensitivity response to insect allergens but indicate that IBDH in
      Icelandic horses may have a different pathogenesis from the same condition in
      other breeds.

PMID- 16574246
TI  - Elevation of IL-12 p40 and its antibody in myasthenia gravis with thymoma.
AB  - We examined the serum levels of cytokines, interferon (IFN)-alpha, IFN-gamma,
      interleukin (IL)-4, IL-12 p40, and IL-12 p70; those that affect the T helper 1
      and 2 balance in patients with myasthenia gravis (MG). Among the cytokines
      tested, only IL-12 p40, together with the serum titer of anti-IL-12 p40 antibody,
      was significantly elevated in MG with thymoma. Their elevation was independent of
      the histopathology of thymoma. Thymectomy decreased the levels of IL-12 p40
      accompanied by the anti-acetylcholine receptor antibody, but not anti-IL-12 p40
      antibodies. These data strongly suggest the association of IL-12 p40 and its
      autoantibody with the immunopathology of MG with thymoma.

PMID- 16574247
TI  - Differential effects of chemokines on oligodendrocyte precursor proliferation and
      myelin formation in vitro.
AB  - Chemokines have recently been postulated to have important functions in the
      central nervous system (CNS) in addition to their principal role of directional
      migration of leukocytes. In particular, it has been shown that chemokines may
      play a role in the regulation of oligodendrocyte biology. Here, we have chosen to
      study the role of certain chemokines in regulating myelination. We have used the
      murine oligodendrocyte precursor-like cell line, Oli-neu, and primary mixed
      cortical cultures as experimental systems to assess their activities on
      oligodendrocyte precursor proliferation and developmental in vitro myelination.
      GRO-alpha, IL-8, SDF-1alpha and RANTES dose-dependently increased proliferation
      of this mouse A2B5 precursor-like cell line, while MCP-1 did not. Furthermore,
      the CXC chemokines GRO-alpha, IL-8 and SDF-1alpha stimulated myelin basic protein
      synthesis in a dose-dependent manner in primary myelinating cultures and enhanced
      myelin segment formation in this system, while the CC chemokines MCP-1 and RANTES
      did not. We also demonstrate that the receptor for SDF-1alpha, CXCR4, is
      expressed in mixed cortical cultures by PDGFalphaR positive oligodendrocyte
      precursors (OLPs) as well as by Oli-neu cells. SDF-1alpha induced proliferation
      in primary mixed cultures and the Oli-neu cell line was mediated through this
      receptor. We propose, therefore, that CXC chemokines and in particular SDF-1alpha
      regulates CNS myelination via their effects on cells of the oligodendrocyte
      lineage, specifically stimulation of OLP proliferation.

PMID- 16574248
TI  - Corrosive injury of the oesophagus in children.
AB  - OBJECTIVE: This study examined a cohort of pediatric patients treated for
      suspected corrosive injury of the oesophagus in the ENT department between 1994
      and 2003. METHODS: During the study period we examined 337 patients. All patients
      were treated according to an individual diagnostico-therapeutic protocol that
      included: foremost, early rigid oesophagoscopy; intensive medical therapy;
      nasogastric tube placement; and/or surgical intervention. RESULTS: Our proposed
      system of grading on a scale from 0 to 4 was used to classify the findings upon
      oesophagoscopy. One hundred eighty eight patients (55.7%) had a negative exam;
      1st degree corrosive injury was present in 58 patients (17.4%); 2nd and 3rd
      degree injury in 81 patients (24%); and 4th degree was found in 10 patients (3%).
      CONCLUSIONS: Because the endoscopic findings were positive in 44% of patients
      with suspected corrosive injury, early rigid oesophagoscopy is indicated in all
      patients suspected of having corrosive injury even in the absence of clinical
      symptoms.

PMID- 16574249
TI  - Lateral graft type 1 tympanoplasty using AlloDerm for tympanic membrane
      reconstruction in children.
AB  - OBJECTIVES: To describe the lateral graft type 1 tympanoplasty technique using
      AlloDerm for tympanic membrane reconstruction in children and to compare its
      surgical and audiometric outcomes with the traditional underlay type 1
      tympanoplasty. METHODS: The records of 34 consecutive children undergoing type 1
      tympanoplasty between 2004 and 2005 were reviewed; 18 received lateral graft
      tympanoplasty with AlloDerm and 16 received underlay tympanoplasty (8 AlloDerm
      and 8 temporalis fascia). Pre- and post-surgical audiograms, speech reception
      threshold, closure rate and complication rate were evaluated using one-way and
      repeated measures ANOVAs. RESULTS: Children who underwent lateral graft type 1
      tympanoplasty pre-operatively had larger tympanic membrane perforations, worse
      pure tone averages, air bone gaps and speech reception thresholds as compared
      with children undergoing underlay type 1 tympanoplasty (P<0.001). Pure tone
      averages and air bone gaps improved significantly with surgery in both lateral
      and underlay type 1 tympanoplasty groups (P<0.05), with both groups achieving
      comparable postoperative audiometric outcomes (P>0.01). The lateral graft group
      demonstrated a higher perforation closure rate (94%) as compared with both
      underlay groups (88%). Complication rates were virtually non-existent.
      CONCLUSIONS: Despite larger perforations and worse pre-operative audiometric
      scores, children who underwent lateral graft type 1 tympanoplasty achieved
      comparable postoperative audiometric results and perforation closure rates as
      compared with children who underwent underlay type 1 tympanoplasty. Results
      suggest that lateral graft type 1 tympanoplasty using AlloDerm is effective for
      tympanic membrane reconstruction in children and should be used when temporalis
      fascia is not available or the extent of the perforation limits its use.

PMID- 16574251
TI  - Tympanometry of a diverse group of preschool aged children.
AB  - OBJECTIVE: Ethnicity has been previously described as a risk factor for middle
      ear disease. Little data exist on the presence of middle ear disease based on
      tympanometry screening comparing Asian children and children of other races.
      METHODS: Two hundred and seventy children aged 3-5 were screened with
      tympanometry at six Head Start sites in St. Paul, Minnesota during the months of
      September and October of 2004. Gender, age, and race/ethnicity was recorded and
      entered into a database, along with values for canal volume, static admittance,
      peak pressure, and tympanometric width. RESULTS: Criteria for abnormal
      tympanometry were based on American Speech-Language Hearing Association (ASHA)
      recommendations for a failed tympanogram for 1-5 year olds (admittance <0.3 mmho
      or width >200 daPa). There were no statistically significant differences in
      failure rates between males and females. There were, however, more failures for
      Asian (predominantly Hmong) children compared to children of other
      races/ethnicities after adjusting for age and gender differences (OR=6.39, CI
      3.65-11.2, p<0.001) and for children <4-years-old compared to children 4-5-years
      old after adjusting for race and gender differences (OR=1.99, CI 1.03-3.84,
      p<0.05). CONCLUSIONS: Asian children were more than six times as likely to fail
      tympanometry as children of other races/ethnicities. The explanation for this
      difference is likely to be multifactorial, and further research is needed to
      characterize this difference.

PMID- 16574250
TI  - Prevalence of auditory neuropathy/synaptopathy in a population of children with
      profound hearing loss.
AB  - OBJECTIVE: To examine the prevalence of auditory neuropathy/synaptopathy (AN/AS)
      in a cohort of children with profound hearing loss. METHODS: From 1997 until
      2004, 5190 children, aged 1-15 years, whose hearing ability was uncertain or who
      had risk factors for hearing impairment were investigated with subjective and
      objective hearing tests. Three thousand four hundred and fifteen from these
      children were screened for AN/AS using pure-tone audiometry, impedance
      measurement, transient evoked otoacoustic emissions (TEOAE) and click-evoked
      auditory brainstem responses (ABR). RESULTS: From 3415 patients who participated
      in an ABR and TEOAE assessment, 379 children showed absent or elevated (> or = 80
      dB nHL) ABR thresholds. Within this group we found 32 cases with evidence of
      AN/AS via visible TEOAE and/or cochlear microphonics (CM) coupled with absent
      ABR. In the remaining 3036 children, AN/AS, could be ruled out by means of
      detectable ABR-thresholds and coherent findings in pure-tone audiometry and TEOAE
      assessment. This results in a prevalence of AN/AS of 0.94% within the group at
      risk for hearing loss, compared to 8.44% among profoundly hearing impaired
      children. CONCLUSION: This study shows that AN/AS is a common finding in the
      population of hearing impaired infants. In the majority of our AN/AS children
      (50%, n=16), an early audiological diagnosis was made under the age of 12 months.
      Therefore, clinicians and other health care professionals should generally be
      sensitised for AN/AS in infants, so that an appropriate treatment can promptly be
      initiated. Further research on clinical and pathophysiological aspects is
      necessary to better identify and manage patients suffering from AN/AS.

PMID- 16574252
TI  - Auditory brainstem response in pediatric migraine: during the attack and
      asymptomatic period.
AB  - OBJECTIVE: The aim of this study was to evaluate the hearing parameters of
      children with migraine during ictal and interictal period. METHOD: 16 pediatric
      patients with migraine and normal otolaryngologic examination were evaluated.
      Hearing parameters were assessed with auditory brainstem response (ABR) testing
      between and during the migraine attacks. Binaural absolute latencies of waves I,
      III and V, interpeak latencies I-III, III-V and I-V of ABR in response to 80 dB
      nHL clicks were calculated. Initial findings were compared with those of 20
      healthy volunteers. RESULTS: Peak latencies of wave V and interpeak latencies of
      I-V were prolonged during the attack in migraineurs on the left. The side of
      latency elongation was not affected by the side of headache. When these
      parameters were separately compared for gender, they were prolonged in boys
      during the attack in migraineurs; however in girls, while there was statistically
      significant difference at interpeak latencies of I-V, no significant difference
      was noted at peak latencies of wave V. CONCLUSIONS: ABR waves did not exceed
      clinical norms in migraine patients in headache-free period. But, important
      effects on sensorineural hearing parameters were detected during the attack. Our
      results indicated a transient impairment of the auditory brainstem function
      during the headache in pediatric migraine patients.

PMID- 16574253
TI  - Intracerebroventricular injection of L-serine analogs and derivatives induces
      sedative and hypnotic effects under an acute stressful condition in neonatal
      chicks.
AB  - Four experiments were conducted to clarify the central functions of L-serine and
      its analogs on an acute stressful condition. Intracerebroventricular (i.c.v.)
      injection of L-serine (0.21, 0.42 and 0.84 micromol) attenuated stress responses
      in a dose-dependent fashion, as well as induced sleep, in Experiment 1. The
      effects of L- and D-serine in Experiment 2, those of L-serine, phosphoserine,
      acetylserine and L-cysteine in Experiment 3 and those of L-serine, glycine and
      lysophosphatidylserine in Experiment 4 were compared at an equimolar basis (0.84
      micromol). D-Serine, proposed as an endogenous agonist of N-methyl-D-aspatate
      (NMDA) receptor, did not have sedative and hypnotic effects as observed with L
      serine. In contrast, all the analogs and derivatives of L-serine had a sedative
      effect, although with a different manner in several behavioral markers of stress
      such as spontaneous activity and distress vocalizations. No significant changes
      in plasma corticosterone concentration were observed in any experiment. Taken
      together, the i.c.v. injection of L-serine analogs and its derivatives have
      sedative and hypnotic effects under an acute stressful condition, which does not
      involve the hypothalamic-pituitary-adrenal axis. In conclusion, L-serine may be
      effective in improving anxiety or sleep disorders induced by psychological
      stressor.

PMID- 16574254
TI  - Behavioral effects of opioid subtypes compared with benzodiazepines in the
      staircase paradigm.
AB  - Opioid abuse is frequently associated with the abuse of benzodiazepines (BZ).
      Despite the fact that benzodiazepines and opioids act at totally separate
      receptor sites and through different biochemical and pharmacological mechanisms,
      they obviously interact with each other at some level. The present study was
      designed to investigate the behavioral effects of agents with activity on the
      opioid system and with the benzodiazepine receptor complex in the staircase
      paradigm. The benzodiazepine agonist lorazepam was used as a reference drug and
      showed a benzodiazepine effect: it reduced the rearing activity in mice in a dose
      dependent manner, at doses that did not suppress climbing. Dissociation between
      the rearing and climbing behavior was not obtained with the administration of the
      opioid benzodiazepine, tifluadome, although tifluadome was antagonized by the BZ
      antagonist, flumazenil and not by naloxone, an opioid antagonist. An
      administration of opioids that act on the different subtype receptors morphine,
      U50 and SNC80, induced a dose dependent decrease in both the rearing and climbing
      activity, meaning no behavioral dissociation. Naloxone was found to have an
      antagonistic effect on morphine and U50-488H (micro and kappa subtype receptors,
      respectively), but no antagonistic effect on the delta subtype receptor agonist,
      SNC80. The administration of nalorphine to mice had no effect on both the rearing
      and climbing, in the staircase paradigm. When combining naloxone with the
      mentioned nalorphine, results showed the same effect, which was achieved with all
      the other opiates. This data, once again, supports the validity of the mouse
      staircase test for the identification of anxiolytic agents with a GABA(A)
      receptor complex-mediated activity, and for the ability to differentiate between
      diverse effects of the different opioids.

PMID- 16574255
TI  - Molecular cloning and characterization of Schistosoma mansoni Ftz-F1 interacting
      protein-1 (SmFIP-1), a novel corepressor of the nuclear receptor SmFtz-F1.
AB  - In order to characterize protein cofactors of the Schistosoma mansoni nuclear
      receptor SmFtz-F1, we have screened a yeast two-hybrid adult worm cDNA library
      using a construct expressing the D, E and F domains of SmFtz-F1 as bait. One of
      the selected clones encoded a sequence without homologues in any other species,
      apart from Schistosoma japonicum. The complete sequence was obtained by 5' and 3'
      rapid amplification of cDNA ends (RACE) and comprised 3660 nucleotides with an
      open reading frame of 788 amino acids. The gene is expressed at all schistosome
      life cycle stages at a 5-11-fold higher level than SmFtz-f1. The protein, named
      SmFIP-1, interacted with SmFtz-F1 in a GST pull-down assay and in a mammalian two
      hybrid assay in CV-1 cells. Although SmFIP-1 contains a consensus NR box (LXXLL)
      this was not involved in the interaction with SmFtz-F1. However, interaction did
      depend on the AF2-AD motif in the nuclear receptor ligand binding domain.
      Deletion analysis showed that the C-terminal moiety of SmFIP-1 was involved in
      the binding, but this could not be localized to a particular motif, suggesting
      that the binding may be conformation-dependent. Finally, SmFIP-1 markedly
      repressed SmFtz-F1-mediated transcription in a dose-dependent manner from the
      SmFtz-f1 gene promoter demonstrating that SmFIP-1 is a schistosome-specific
      transcriptional corepressor.

PMID- 16574256
TI  - Combinatorial regulation modules on GmSBP2 promoter: a distal cis-regulatory
      domain confines the SBP2 promoter activity to the vascular tissue in vegetative
      organs.
AB  - The Glycine max sucrose binding protein (GmSBP2) promoter directs phloem-specific
      expression of reporter genes in transgenic tobacco. Here, we identified cis
      regulatory domains (CRD) that contribute with positive and negative regulation
      for the tissue-specific pattern of the GmSPB2 promoter. Negative regulatory
      elements in the distal CRD-A (-2000 to -700) sequences suppressed expression from
      the GmSBP2 promoter in tissues other than seed tissues and vascular tissues of
      vegetative organs. Deletion of this region relieved repression resulting in a
      constitutive promoter highly active in all tissues analyzed. Further deletions
      from the strong constitutive -700GmSBP2 promoter delimited several intercalating
      enhancer-like and repressing domains that function in a context-dependent manner.
      Histochemical examination revealed that the CRD-C (-445 to -367) harbors both
      negative and positive elements. This region abolished promoter expression in
      roots and in all tissues of stems except for the inner phloem. In contrast, it
      restores root meristem expression when fused to the -132pSBP2-GUS construct,
      which contains root meristem expression-repressing determinants mapped to the 44
      bp CRD-G (-136 to -92). Thus, the GmSBP2 promoter is functionally organized into
      a proximal region with the combinatorial modular configuration of plant promoters
      and a distal domain, which restricts gene expression to the vascular tissues in
      vegetative organs.

PMID- 16574257
TI  - dps expression in Escherichia coli O157:H7 requires an extended -10 region and is
      affected by the cAMP receptor protein.
AB  - The DNA binding protein from starved cells (Dps) is a general stress protein that
      provides Escherichia coli protection from osmotic, oxidative, and acid stresses.
      While Dps production and accumulation is primarily associated with stationary
      phase, during log phase, this protein protects against oxidative stress in an
      OxyR-dependent manner. In this study, evidence is provided that expands the role
      of Dps in acid tolerance to both log- and stationary-phase E. coli O157:H7. The
      transcription of dps occurred in log-phase cells without OxyR or stress and was
      upregulated during entry into stationary phase. The expression in log and
      stationary phase involved sigma70 and sigmas, respectively, with both sigma
      factors recognizing the same promoter region. Site-directed mutagenesis
      identified an extended -10 region that was essential to both sigma70 and sigmas
      transcription of dps. cAMP receptor protein (CRP) was found to repress dps
      expression as a crp mutant had a significant increase in the dps mRNA level.
      However, a CRP binding site was not found in the dps promoter and upregulation of
      dps in the crp mutant was absent in a crp rpoS double mutant. The findings from
      this study demonstrated that dps was expressed at a basal level during growth,
      both sigma70- and sigmas-driven transcription required an extended -10, and CRP
      repression is mediated through the alternative sigma factor sigmas (rpoS).

PMID- 16574259
TI  - Get the balance right: mitofusins roles in health and disease.
AB  - Mitochondria are highly dynamic organelles exhibiting an elaborate morphology and
      fine structure. Fusion and fission processes contribute to the maintenance and
      dynamics of mitochondrial morphology. The Mitofusins, a class of evolutionary
      conserved GTPases of the mitochondrial outer membrane, are essential for the
      controlled fusion of mitochondrial membranes. Genetic and biochemical data
      propose a model in which functional domains, such as the GTPase domain and the C
      terminally located coiled coil structure, act in an orchestrated manner to
      coordinate the tethering and mitochondrial outer membrane fusion. In addition,
      recent reports shed new light on the physiological importance of Mitofusin
      function suggesting a role in mitochondrial metabolism, apoptosis as well as
      cellular signalling. Mutations identified in the human Mfn2 gene from patients
      with the peripheral neuropathy Charcot-Marie-Tooth Type 2A invoke a direct
      correlation between mitochondrial morphology and function.

PMID- 16574258
TI  - Mitochondrial membrane dynamics, cristae remodelling and apoptosis.
AB  - Mitochondria form a highly dynamic reticular network in living cells, and undergo
      continuous fusion/fission events and changes in ultrastructural architecture.
      Although significant progress has been made in elucidating the molecular events
      underlying these processes, their relevance to normal cell function remains
      largely unexplored. Emerging evidence, however, suggests an important role for
      mitochondrial dynamics in cellular apoptosis. The mitochondria is at the core of
      the intrinsic apoptosis pathway, and provides a reservoir for protein factors
      that induce caspase activation and chromosome fragmentation. Additionally,
      mitochondria modulate Ca2+ homeostasis and are a source of various metabolites,
      including reactive oxygen species, that have the potential to function as second
      messengers in response to apoptotic stimuli. One of the mitochondrial factors
      required for activation of caspases in most intrinsic apoptotic pathways,
      cytochrome c, is largely sequestered within the intracristae compartment, and
      must migrate into the boundary intermembrane space in order to allow passage
      across the outer membrane to the cytosol. Recent evidence argues that inner
      mitochondrial membrane dynamics regulate this process. Here, we review the
      contribution of mitochondrial dynamics to the intrinsic apoptosis pathway, with
      emphasis on the inner membrane.

PMID- 16574260
TI  - Early repolarization syndrome: is it always benign?
AB  - Early repolarization syndrome is a well-recognized idiopathic
      electrocardiographic phenomenon characterized by prominent J wave and ST-segment
      elevation predominantly in left precordial leads. The syndrome shares remarkable
      cellular, ionic, and electrocardiographic similarities with the Brugada syndrome
      and idiopathic ventricular fibrillation (a variant of the Brugada syndrome with
      ST-segment elevation in inferior leads). Although early repolarization syndrome
      is considered a benign entity, its arrhythmogenic potential still remains
      unknown. We report the case of a 39-year-old male with a family history of sudden
      death and an electrocardiogram consistent with early repolarization syndrome.
      Diagnostic dilemmas are discussed.

PMID- 16574261
TI  - Application of "robust" methods to the analysis of collaborative trial data using
      bacterial colony counts.
AB  - We describe techniques for the application of two methods, robust to the presence
      of "outliers", to the hierarchical analysis of variance of bacterial count data
      from collaborative trials. The techniques are tested against both artificially
      generated data with known distributional parameters and actual trial results
      containing outliers. The relative merits of the robust methods are discussed in
      comparison with conventional ANOVA techniques.

PMID- 16574262
TI  - Laccases: blue enzymes for green chemistry.
AB  - Laccases are oxidoreductases belonging to the multinuclear copper-containing
      oxidases; they catalyse the monoelectronic oxidation of substrates at the expense
      of molecular oxygen. Interest in these essentially "eco-friendly" enzymes--they
      work with air and produce water as the only by-product--has grown significantly
      in recent years: their uses span from the textile to the pulp and paper
      industries, and from food applications to bioremediation processes. Laccases also
      have uses in organic synthesis, where their typical substrates are phenols and
      amines, and the reaction products are dimers and oligomers derived from the
      coupling of reactive radical intermediates. Here, we provide a brief discussion
      of this interesting group of enzymes, increased knowledge of which will promote
      laccase-based industrial processes in the future.

PMID- 16574263
TI  - Patient set-up verification by infrared optical localization and body surface
      sensing in breast radiation therapy.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to investigate the clinical
      application of a technique for patient set-up verification in breast cancer
      radiotherapy, based on the 3D localization of a hybrid configuration of surface
      control points. MATERIALS AND METHODS: An infrared optical tracker provided the
      3D position of two passive markers and 10 laser spots placed around and within
      the irradiation field on nine patients. A fast iterative constrained minimization
      procedure was applied to detect and compensate patient set-up errors, through the
      control points registration with reference data coming from treatment plan
      (markers reference position, CT-based surface model). RESULTS: The application of
      the corrective spatial transformation estimated by the registration procedure led
      to significant improvement of patient set-up. Median value of 3D errors affecting
      three additional verification markers within the irradiation field decreased from
      5.7 to 3.5 mm. Errors variability (25-75%) decreased from 3.2 to 2.1 mm. Laser
      spots registration on the reference surface model was documented to contribute
      substantially to set-up errors compensation. CONCLUSIONS: Patient set-up
      verification through a hybrid set of control points and constrained surface
      minimization algorithm was confirmed to be feasible in clinical practice and to
      provide valuable information for the improvement of the quality of patient set
      up, with minimal requirement of operator-dependant procedures. The technique
      combines conveniently the advantages of passive markers based methods and surface
      registration techniques, by featuring immediate and robust estimation of the set
      up accuracy from a redundant dataset.

PMID- 16574264
TI  - A low molecular weight fraction of polyethylenimine (PEI) displays increased
      transfection efficiency of DNA and siRNA in fresh or lyophilized complexes.
AB  - RNA interference (RNAi) represents a powerful method for specific gene silencing.
      It is mediated through small double-stranded RNA molecules (small interfering
      RNAs, siRNAs) which sequence-specifically trigger the cleavage and subsequent
      degradation of their target mRNA. One critical factor that determines the success
      of RNAi is the ability to deliver intact siRNAs into target cells.
      Polyethylenimines (PEIs) are synthetic polymers with a high cationic charge
      density which function as transfection reagents based on their ability to compact
      DNA or RNA into complexes. This paper describes the application of lyophilized
      PEI/siRNA complexes based on a novel polyethylenimine. By fractionation of a
      commercially available 25-kDa PEI using gel permeation chromatography, a low
      molecular weight polyethylenimine (PEI F25-LMW) with superior transfection
      efficacy and low toxicity in various cell lines is obtained. Complexes formed in
      5% glucose, but not in 150 mM NaCl, can be lyophilized and reconstituted without
      loss of transfection efficacy. Furthermore, PEI F25-LMW is able to complex and
      fully protect siRNAs against nucleolytic degradation, and delivers siRNAs into
      cells where they display bioactivity. Upon lyophilization and reconstitution of
      PEI F25-LMW-based siRNA complexes, siRNAs are still able to efficiently induce
      RNAi. To further demonstrate their applicability, lyophilized PEI/siRNA complexes
      are employed for targeting of the growth factor VEGF. Treatment of PC-3 prostate
      carcinoma cells with fresh or with lyophilized complexes results in decreased
      cell proliferation in different assays due to the siRNA-mediated downregulation
      of VEGF. In conclusion, siRNAs can be applied in lyophilized formulations, and
      lyophilized PEI F25-LMW-based siRNA complexes represent a powerful, inexpensive,
      non-toxic and simple ready-to-use platform for the specific and efficient
      targeting of genes in vitro.

PMID- 16574265
TI  - Etoposide nanocarriers suppress glioma cell growth by intracellular drug delivery
      and simultaneous P-glycoprotein inhibition.
AB  - In cancer treatment, efficient therapeutic strategies could be impeded by
      cellular mechanisms such as the multidrug resistance. Recently, drug-loaded
      nanoparticles have been reported to be useful, since they allow entering the
      cancer cell and act as an intracellular anti-cancer drug reservoir. A new
      approach is proposed here by the use of lipid nanocapsules (LNC) which were
      hypothesized to reverse multidrug resistance additionally by their P-glycoprotein
      (P-gp) inhibiting surfactant. LNC (mean diameter 25 to 100 nm) were loaded with
      etoposide, tested for the drug release and their efficiency to reduce cell growth
      in cell culture for C6, F98, and 9L glioma cell lines. Sustained etoposide
      release can be provided over a period of 1 week (t10%: 1.4+/-0.1h; t50%: 15.9+/
      2.8h). The P-gp inhibiting activity in-vitro was found to be independent from the
      LNC size. In cell culture, an internalization of LNC was observed in all glioma
      cell types. Etoposide LNC showed a generally higher efficiency than the drug
      solution while blank LNC were found to be less inhibitory than the pure drug at
      equivalent concentrations (IC50: C6: etoposide: 25.2 microM; LNC: 2.6-8.9 microM,
      F98: etoposide: 46.5 microM; LNC: 1.4-14.7 microM, 9L: etoposide: 58.2 microM;
      LNC: 4.4-12.7 microM). This effect was found to be particle size dependent within
      a range of an 8- (C6) to 33-fold (F98) increased cytotoxicity for smallest
      particles. When cells were incubated with etoposide solution in the presence of
      blank LNC, a slight growth inhibition was observed, however, distinctly lower
      than the drug-trapping particles. Moreover, cell toxicity on astrocytes was
      similar for etoposide LNC and etoposide solution. The mechanism of action of
      etoposide LNC was proposed to be a cell uptake followed by a sustained drug
      release from the LNC in combination with an intracellular P-gp inhibition
      ensuring a higher anticancer drug concentration inside the cancer cells.

PMID- 16574266
TI  - Ex vivo gene therapy approaches to cartilage repair.
AB  - Degeneration of articular cartilage is one of the great clinical challenges that
      still lack a convincing therapeutic solution. Traumatically induced lesions and
      final stages of osteoarthritis with substantial loss of cartilage tissue require
      the generation of new hyaline cartilage, because significant endogenous repair
      does not occur. Current joint-preserving surgical approaches, however, mostly
      lead to fibrous repair tissue that is rapidly degraded. In experimental studies,
      several differentiation factors have been shown to stimulate chondrogenesis,
      promoting the formation of functionally acceptable cartilage-like repair tissue.
      Cell-mediated transfer of the respective genes may ideally combine the supply of
      a chondrogenic cell population with the production of such factors directly at
      the site of the lesion. The treatment of earlier disease stages aims both at the
      protection of the remaining cartilage from further degradation and a stimulation
      of cartilage anabolism. Various studies proved the administration of anti
      catabolic or anti-inflammatory cytokines into joints affected by cartilage
      destruction to be beneficial. However, the clinical utility of intraarticular
      protein application is limited by the short half-lives of such proteins in vivo.
      The transfer of cells over-expressing the respective genes may provide a more
      sustained delivery of the therapeutic molecules and thus be the more economic
      option.

PMID- 16574267
TI  - Intraarticular drug delivery in osteoarthritis.
AB  - Osteoarthritis (OA) is a primarily non-inflammatory, degenerative joint disease
      characterized by progressive loss of articular cartilage, subchondral bone
      sclerosis, osteophyte formation, changes in the synovial membrane, and an
      increased volume of synovial fluid with reduced viscosity and hence changed
      lubrication properties. As OA is the most common type of arthritis and a leading
      cause of disability, there is a largely unmet medical need for disease-modifying
      and symptomatic treatment. Due to the localized nature of the disease,
      intraarticular (IA) drug injection is an attractive treatment approach for OA.
      The various glucocorticoid and hyaluronic acid (HA) formulations, which are
      currently available on the market for IA treatment, provide only short-term pain
      relief or/and often do not provide adequate pain relief. The available oral drugs
      for symptomatic treatment also have shortcomings, most notably side effects.
      Therefore, there is still a large unmet need for novel OA drugs, which provide
      effective long-term pain relief and/or have disease-modifying properties. To
      achieve long-term drug exposure, different established formulations such as
      suspensions and hydrogels, and also novel approaches such as lipid based
      formulations and nano- or microparticles are currently in development. The
      development of novel drugs in combination with new formulations for IA treatment
      of OA, represents a promising approach in this challenging area of research.

PMID- 16574268
TI  - Cartilage tissue engineering for degenerative joint disease.
AB  - Pain in the joint is often due to cartilage degeneration and represents a serious
      medical problem affecting people of all ages. Although many, mostly surgical
      techniques, are currently employed to treat cartilage lesions, none has given
      satisfactory results in the long term. Recent advances in biology and material
      science have brought tissue engineering to the forefront of new cartilage repair
      techniques. The combination of autologous cells, specifically designed scaffolds,
      bioreactors, mechanical stimulations and growth factors together with the
      knowledge that underlies the principles of cell biology offers promising avenues
      for cartilage tissue regeneration. The present review explores basic biology
      mechanisms for cartilage reconstruction and summarizes the advances in the tissue
      engineering approaches. Furthermore, the limits of the new methods and their
      potential application in the osteoarthritic conditions are discussed.

PMID- 16574269
TI  - Antisense strategies in degenerative joint diseases: sense or nonsense?
AB  - Oligodeoxynucleotides, ribozymes, and RNA interference make part of the antisense
      strategy, a new tool proposed to conquer cancer, viral infections, as well as
      cardiovascular and rheumatic diseases. The silencing effect of antisense
      strategies is both highly specific and potent - and only requires that the
      sequence of the target RNA is known. However, so far neither RNAi nor ribozymes
      have been approved for clinical use and only a single antisense agent is on the
      market. In the context of degenerative joint diseases, experimental data in the
      field of antisense strategies are still rare. Several studies from rheumatoid
      arthritis (RA), an inflammatory condition that leads to the progressive
      destruction of cartilage and bone within affected joints, however revealed
      promising results and taught us important lessons that might also be useful in
      therapeutic approaches for osteoarthritis (OA). To introduce these therapies in
      clinical practice, however, several hurdles still have to be overcome.

PMID- 16574270
TI  - Analysis of c-kit expression in small cell lung cancer: prevalence and prognostic
      implications.
AB  - c-kit, a growth factor receptor with tyrosine kinase activity, plays an important
      role in the biology of cancer. Its expression has been documented in several
      malignancies. We performed a retrospective study in 85 patients diagnosed with
      small cell lung cancer (SCLC) to determine the prevalence and role of c-kit as a
      possible prognostic marker in this lung cancer malignancy. Demographic and
      clinical data were obtained from patient charts. c-kit, analyzed as
      immunohistochemical expression in paraffin-embedded tumour tissues, was observed
      in 60% of patients. All patients were former or present smokers. At diagnosis,
      46% of the patients had limited disease (LD) and 54% extended disease (ED). c-kit
      expression was observed in 59% of LD and 61% of ED patients (p=0.4). Patients
      received a median of 4 cycles first-line combination chemotherapy (platinum and
      etoposide). In LD patients, time to progression (TTP) was 11.5 months in c-kit
      (+) versus 5.9 in c-kit (-) patients (p=0.14), and median survival 15.4 and 12.8
      months, respectively (p=0.33). In the ED group, TTP was 5.5 months in c-kit (+)
      versus 3.8 in c-kit (-) patients (p=0.34), whereas median survival was 6.3 and
      7.9 months, respectively (p=0.45). With the limited number of patients in mind,
      our findings tended towards an association between c-kit expression and survival
      in the LD group.

PMID- 16574271
TI  - Imaging of gefitinib-related interstitial lung disease: multi-institutional
      analysis by the West Japan Thoracic Oncology Group.
AB  - Gefitinib (Iressatrade mark) is an epidermal growth factor receptor tyrosine
      kinase inhibitor that has been approved for the treatment of lung cancer in
      Japan, however, after marketing several cases of severe pulmonary toxicity were
      reported. The West Japan Thoracic Oncology Group conducted an independent survey
      of acute pulmonary toxicity and interstitial lung disease (ILD) caused by
      gefitinib in its member's institutions. The purpose of this study was to clarify
      the image characteristics of ILD caused by the molecular-targeting drug
      gefitinib. A total of 1976 patients had been treated with gefitinib between
      August and December 2002, and 102 of them were suspected of having acute
      pulmonary toxicity and ILD. A final definite diagnosis of gefitinib-induced ILD
      was made by at least three radiologists based on a review and analysis of the
      chest radiography and CT findings plus the clinical data in the medical records.
      The imaging findings were classified into four patterns: (A) a nonspecific area
      with ground-glass attenuation, (B) a multifocal area of airspace consolidations,
      (C) patchy distribution of ground-glass attenuation accompanied by interlobar
      septal thickening, and (D) extensive bilateral ground-glass attenuation or
      airspace consolidations with traction bronchiectasis. CT as well as chest
      radiography had been performed in 65 of the 102 patients at the onset of ILD, and
      chest radiography alone had been performed in 26. After excluding 11 cases with
      insufficient data and 21 cases concluded to be other pulmonary diseases, 70
      patients were diagnosed with gefitinib-induced ILD. Finally, the diagnostic image
      findings were classified as pattern A in 29 cases, pattern B in 7 cases, pattern
      C in 3 cases, pattern D in 20 cases and others in 11 cases. The CT images were
      classified as pattern A, B, C, and D in 24, 7, 1, and 12 cases, respectively. The
      mortality rate was significantly higher in the patients with pattern D than the
      other patterns. Pattern D were thought to represent the features of diffuse
      alveolar damage. In conclusion, the molecular-targeting drug gefitinib induces
      pulmonary toxicity at a certain rate and the imaging findings of ILD induced by
      gefitinib are similar to those of pulmonary toxicity induced by conventional
      antineoplastic agents.

PMID- 16574272
TI  - Geophysical constraints on contaminant transport modeling in a heterogeneous
      fluvial aquifer.
AB  - Approximately 3000 measurements of hydraulic conductivity in over 50 flowmeter
      boreholes were available at the Macro-Dispersion Experiment (MADE) site in
      Columbus, Mississippi, USA to quantify the heterogeneity in hydraulic
      conductivity at the site scale. This high-density measurement approach is perhaps
      infeasible for time and expense in typical groundwater remediation sites. A
      natural-gradient tracer experiment from the MADE site was simulated by a
      groundwater flow and solute transport model incorporating direct-current (DC)
      resistivity data collected over the observed plume location. Hydraulic
      conductivity from one borehole collected during the original site
      characterization was used to calibrate the electrical resistivity data to
      hydraulic conductivity using a previously derived log-log relationship.
      Application of this relationship, using site-specific empirical constants
      determined from the data, transforms the 3D electrical resistivity data into a 3D
      description of hydraulic conductivity that can be used in groundwater models. The
      validity of this approach was tested by using the geophysically derived hydraulic
      conductivity representation in numerical simulations of the natural-gradient
      tracer experiment. The agreement between the simulated and observed tracer plumes
      was quantified to gauge the effectiveness of geophysically derived and flowmeter
      based representations of the hydraulic conductivity field. This study
      demonstrates that a highly heterogeneous aquifer can be modeled with minimal
      hydrological data supplemented with geophysical data at least as well as previous
      models of the site using purely hydrologic data.

PMID- 16574273
TI  - Microbial bioavailability of pyrene in three laboratory-contaminated soils under
      aerobic and anaerobic conditions.
AB  - Changes in bioavailability of pyrene in three uncontaminated soils were examined
      under aerobic and anaerobic conditions. Three soils were aerobically aged with
      pyrene and [(14)C]pyrene for 63 days, then incubated with water, nitrate, or
      sulfate under aerobic or anaerobic conditions for one year. Under aerobic
      conditions, microorganisms in two soils mineralized 58-82% of the added
      [(14)C]pyrene. The two soils amended with nitrate were seen to have enhanced
      aerobic mineralization rates. In one of these soils, non-extractable pyrene was
      seen to decrease over the course of the study due to desorption and
      mineralization, nitrate amendment enhanced this effect. Under anaerobic
      conditions, generated with a N(2):CO(2)(g) headspace, two soils with nitrate or
      sulfate amendment showed an increase in extractable [(14)C]pyrene at 365 days
      relative to inhibited controls, presumably due to microbially mediated oxidation
      reduction potential and pH alteration of the soil environment. These observations
      in different soils incubated under aerobic and anaerobic conditions have
      important implications relative to the impact of microbial electron acceptors on
      bioavailability and transport of non-polar organic compounds in the environment
      suggesting that, given enough time, under the appropriate environmental
      conditions, non-extractable material becomes bioavailable. This information
      should be considered when assessing site specific exposure risks at PAH
      contaminated locations.

PMID- 16574275
TI  - The sweet tooth hypothesis: how fruit consumption relates to snack consumption.
AB  - Building on prior work related to taste preferences of fruit lovers, we
      investigate the "sweet tooth" hypothesis. First, using CSFII survey data, we show
      that fruit consumption is more highly related to sweet snack consumption than it
      is to salty snack consumption. Second, a follow-up study with a different
      population supports the relationship by showing that sweet snack consumption is
      more related to fruit consumption than it is to vegetable consumption. Knowing
      that people who frequently eat sweet snacks may be predisposed to increasing
      their fruit consumption will enable better targeting and tailoring of educational
      efforts, such as those used in the 5-a-Day for Better Health campaign.

PMID- 16574276
TI  - An antifungal protein from the pea Pisum sativum var. arvense Poir.
AB  - An antifungal protein with a molecular mass of 11 kDa and a lysine-rich N
      terminal sequence was isolated from the seeds of the pea Pisum sativum var.
      arvense Poir. The antifungal protein was unadsorbed on DEAE-cellulose but
      adsorbed on Affi-gel blue gel and CM-cellulose. It exerted antifungal activity
      against Physalospora piricola with an IC50 of 0.62 microM, and also antifungal
      activity against Fusarium oxysporum and Mycosphaerella arachidicola. It inhibited
      human immunodeficiency virus type 1 reverse transcriptase with an IC50 of 4.7
      microM.

PMID- 16574277
TI  - Ghrelin stimulates food intake and growth hormone release in rats with thermal
      injury: synthesis of ghrelin.
AB  - Ghrelin, a 28-residue octanoylated peptide recently isolated from the stomach,
      exhibits anti-cachectic properties through regulating food intake, energy
      expenditure, adiposity, growth hormone secretion and immune response. Burn injury
      induces persistent hypermetabolism and muscle wasting. We therefore hypothesized
      that ghrelin may also play a role in the pathophysiology of burn-induced
      cachexia. Overall ghrelin expression in the stomach over 10 days after burn was
      significantly decreased (p = 0.0003). Total plasma ghrelin was reduced 1 day
      after burn. Thus, changes in ghrelin synthesis and release may contribute to burn
      induced dysfunctions. Ghrelin (30 nmol/rat, i.p.) greatly stimulated 2 h food
      intake in rats on five separate days after burn and in control rats. On post-burn
      day 15, plasma growth hormone levels were significantly lower than in controls,
      and this was restored to normal levels by ghrelin (10 nmol/rat, i.p.). These
      observations suggest that ghrelin retains its ability to favorably modulate both
      the peripheral anabolic and the central orexigenic signals, even after thermal
      injury despite ongoing changes due to prolonged and profound hypermetabolism,
      suggesting that long-term treatment with ghrelin may attenuate burn-induced
      dysfunctions.

PMID- 16574278
TI  - A novel approach to identifying beta-secretase inhibitors: bis-statine peptide
      mimetics discovered using structure and spot synthesis.
AB  - Beta-secretase 1 (BACE1) is an aspartic protease believed to play a critical role
      in Alzheimer's disease. Inhibitors of this enzyme have been designed by
      incorporating the non-cleavable hydroxyethylene and statine isosteres into
      peptides corresponding to BACE1 substrate sequences. We sought to develop new
      methods to quickly characterize and optimize inhibitors based on the statine
      core. Minimal sequence requirements for binding were first established using both
      crystallography and peptide spot synthesis. These shortened peptide inhibitors
      were then optimized by using spot synthesis to perform iterative cycles of
      substitution and deletion. The present study resulted in the identification of
      novel "bis-statine" inhibitors shown by crystallography to have a unique binding
      mode. Our results demonstrate the application of peptide spot synthesis as an
      effective method for enhancing peptidomimetic drug discovery.

PMID- 16574279
TI  - Effect of Abeta exposure on the mRNA expression patterns of voltage-sensitive
      calcium channel alpha 1 subunits (alpha 1A-alpha 1D) in human SK-N-SH
      neuroblastoma.
AB  - Evidence for loss of Ca(2+) homeostasis through voltage-sensitive Ca(2+) channels
      (VSCCs) contribution to neuronal degeneration induced by beta-amyloid protein
      (Abeta) is considerable and rapidly increasing. Thus, the expression patterns of
      four alpha(1) subunits for P/Q (alpha(1A))-, N (alpha(1B))-, and L (alpha(1C) and
      alpha(1D))-type VSCCs before and after Abeta exposure were investigated in human
      SK-N-SH neuroblastoma. Reverse transcription-polymerase chain reaction (RT-PCR)
      analysis showed a constitutive and abundant co-expression of mRNA for alpha(1A)
      and alpha(1D) subunit in control cells. The mRNA expression of another L-type
      subunit alpha(1C) was undetectable in control cells while N-type subunit
      alpha(1B) was relative lower when compared to alpha(1A) and alpha(1D) subunits.
      Interestingly, mRNA levels of alpha(1A), alpha(1B), and alpha(1C) were remarkably
      and time-dependently increased in response to Abeta (20 microM) for 72 h culture
      period. In contrast, the constitutively expressed alpha(1D) mRNA was not further
      modified during Abeta exposure. Western blot analysis of four alpha(1) subunits
      expression was consistent with the findings obtained by RT-PCR. In conclusion,
      our results suggested that P/Q-, N-, as well as L-type Ca(2+) channel genes might
      be existed in SK-N-SH cells. Among them, mRNA for alpha(1A), alpha(1B), and
      alpha(1D) were expressed constitutively while alpha(1C) were inducible.
      Furthermore, Abeta exposure selectively modulates the transcription of alpha(1A),
      alpha(1B), and alpha(1C) subunits. These suggested that except activating of
      existed VSCCs, up-regulation of alpha(1) subunits expression might also
      contribute to Abeta-induced neuronal toxicity and the complex of these VSCCs
      expression may participate in Ca(2+) current disturbance in Alzheimer's disease.

PMID- 16574280
TI  - Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment
      and early Alzheimer's disease.
AB  - Neurofibrillary degeneration in the nucleus basalis and a loss of its cortical
      cholinergic projections are prominent components of the neuropathology in
      Alzheimer's disease (AD). The AD brain is also associated with a degeneration of
      the noradrenergic projections arising from the nucleus locus coeruleus (LC), but
      the time course of this lesion is poorly understood. To determine whether the LC
      displays neurofibrillary abnormalities early in the course of events leading to
      AD, we examined tissue specimens from seven cognitively normal controls and five
      subjects at the stages of mild cognitively impairment (MCI) or early AD. Tyrosine
      hydroxylase immunochemistry was used as a marker of LC neurons while AT8
      immunolabeling visualized abnormal tau associated with neurofibrillary tangles
      and their precursors. Thioflavine-S was used as a marker for fully developed
      tangles. We found that AT8-positive labeling and thioflavine-S positive tangles
      were present in both groups of specimens. However, the percentage of neurons
      containing each of these markers was significantly higher in the cognitively
      impaired group. The MMSE scores displayed a negative correlation with both
      markers of cytopathology. These results indicate that cytopathology in the LC is
      an early event in the age-MCI-AD continuum and that it may be listed among the
      numerous factors that mediate the emergence of the cognitive changes leading to
      dementia.

PMID- 16574281
TI  - Estimating the risk population in relation to influenza vaccination policy.
AB  - There are many small differences in national influenza vaccination polices, some
      are age related and others morbidity related. This study examines a large English
      general practice database for 2003 to estimate the size of the England and Wales
      population at risk because of co-morbidity and to make recommendations on the
      choice of morbidity codes for use when estimating demand for vaccine and in
      auditing medical records to assess vaccination uptake. Morbidity codes relevant
      to the assessment of risk were defined and the database was analysed to estimate
      the annual period prevalence of the various diseases and groups of diseases. A
      set of morbidity codes is recommended which taken together include 3.2% of age
      group 0-14 years, 7.5% of 15-44 years and 16.6% of 45-64 years.

PMID- 16574283
TI  - Recombinant hepatitis B large surface antigen, successfully produced in
      Escherichia coli, stimulates T-cell response in mice.
AB  - A fusion protein consisting of the PA binding domain of anthrax lethal factor
      (LFn) and a codon optimized Hepatitis B virus large surface antigen (LHBsAg)
      expresses well in Escherichia coli. The LFn-LHBsAg fusion protein effectively
      elicits a cell-mediated immune (CMI) response to the hepatitis B viral antigens
      in mice.

PMID- 16574282
TI  - Heterologous prime-boost immunization in rhesus macaques by two, optimally spaced
      particle-mediated epidermal deliveries of Plasmodium falciparum circumsporozoite
      protein-encoding DNA, followed by intramuscular RTS,S/AS02A.
AB  - BACKGROUND: RTS,S/AS02A, a recombinant Plasmodium falciparum vaccine based on the
      circumsporozoite protein (CSP) repeat and C-terminus regions, elicits strong
      humoral and Th1 cell-mediated immunity. In field studies, RTS,S/AS02A reduced
      malaria infection, clinical episodes, and disease severity. Heterologous prime
      boost immunization regimens, optimally spaced, might improve the protective
      immunity of RTS,S/AS02A. METHODS: DNA plasmid encoding P. falciparum CSP (3D7)
      was administered to six experimental groups of rhesus monkeys (N = 5) by gene gun
      (coded as D), followed by a 1/5th human dose of RTS,S/AS02A (coded as R).
      Immunization regimens, including a numeral to denote weeks between immunizations,
      were D-4-R, D-16-R, D-4-D-4-R, D-4-D-16-R, D-16-D-4-R and D-16-D-16-R. A control
      group (N = 5) received a single 1/5th dose of RTS,S/AS02A. Endpoints were
      antibody (Ab) to homologous CSP repeat and C-terminus regions and delayed-type
      hypersensitivity (DTH) to CSP peptides. FINDINGS: Monkeys immunized twice with
      DNA, 16 weeks apart (D-16-D-4-R and D-16-D-16-R), developed higher levels of anti
      C-terminus Abs than control monkeys (p<0.02). No CSP DNA priming regimen
      increased RTS,S/AS02A-induced Ab to CSP repeats. At 16 months after first
      immunization, D-R and D-D-R, but not control, monkeys had histologically
      confirmed DTH reactions against CSP C-terminus, which persisted at repeat testing
      12 months later. INTERPRETATION: Two optimally spaced, particle-mediated
      epidermal deliveries of CSP DNA improved the humoral immunogenicity of a single
      dose of RTS,S/AS02A. Further, CSP DNA prime followed by one dose of RTS,S/AS02A
      gave biopsy proven DTH reactions against CSP C-terminus of up to 2 years
      duration, implying the induction of CD4+ memory T cells. Heterologous prime-boost
      strategies for malaria involving gene gun delivered DNA or more potent vectors,
      administered at optimal intervals, warrant further investigation.

PMID- 16574284
TI  - Geographic and ethnic variations of long-term efficacy and immunogenicity of
      hepatitis B vaccination in Hualien, a HBV hyperendemic area.
AB  - It is uncertain whether immunologic memory persists for 15 years or more after
      immunization and whether the efficacy of universal hepatitis B vaccination
      program (UHBVP) in socio-economically disadvantaged area with hyperendemicity of
      hepatitis B virus (HBV) infection is similar. We assayed hepatitis B surface
      antigen (HBsAg) and antibody to HBsAg (anti-HBs) on 2839 students aged 15 years
      or more born before (N = 248) and after (N = 2591) UHBVP. We found that students
      born after UHBVP had significantly lower positive rate of anti-HBs than those
      born before UHBVP (44.6% versus 75.0%, p<0.0001). Seropositive rate of HBsAg for
      students born after UHBVP was also declined significantly (1.9% versus 9.3%,
      p<0.0001). Preventive fraction of UHBVP on HBsAg-seropositivity was 78% (95%
      confidence interval, 0.64-0.87), which was at least 10% lower than previous
      studies. Preventive fraction in Han Chinese (74%) and Atayal (78%) students were
      lower than Amis students (94%). In 2264 Han Chinese students, preventive fraction
      was 16% lower in those resided in rural than urban areas. These observations
      indicated that UHBVP was less effective in socio-economically disadvantaged area
      where HBV infection was hyperendemic and the long-term efficacy and
      immunogenicity of vaccination were modified by host factors and factors
      associated with urbanization.

PMID- 16574286
TI  - Adjuvanticity of stealth liposomes on the immunogenicity of synthetic gp41
      epitope of HIV-1.
AB  - Present study aims to enhance the efficacy of liposomes as an adjuvant by steric
      protection and strengthen the path of vaccine research. PEG grafted liposomes
      carrying epitopes on their surface showed enhanced adjuvanticity than liposomes
      carrying epitopes for elicitation and prolongation of immune response to an
      antigenic epitope of gp41, a transmembrane protein of HIV-1. The multiples of
      epitope were incorporated onto the surface of liposomes by conjugating them with
      phosphatidylethanolamine that was used in the formulation of liposomes at an
      optimized ratio. Furthermore, the liposomes carrying epitopes on their surface
      were sterically protected by shielding with methoxy-poly(ethylene glycol), mass
      20 kDa. Methoxy-poly(ethylene glycol) was activated to its electrophilic N
      succinimide carbonate derivative, methoxy-poly(ethylene glycol)-N-succinimide
      carbonate, that formed a urethane linkage with the amino group of
      phosphatidylethanolamine. The epitope was covalently coupled to
      phosphatidylethanolamine through an amide bond between the -COOH group of the
      epitope and -NH2 group of phosphatidylethanolamine under the catalysis of 1-ethyl
      3-(3-dimethylaminopropy-1)-carbodiimide. PEG grafted epitopes carrying liposomes
      showed about two times higher immune response and prolonged persistence of
      antibodies than that of liposomes carrying epitopes without PEG moieties.

PMID- 16574285
TI  - Recombinant virus-like particles as a carrier of B- and T-cell epitopes of
      hepatitis C virus (HCV).
AB  - The major aim of the project was the development of virus-like particles (VLP)
      displaying B- and T-cell epitopes of hepatitis C virus (HCV) proteins. To this
      end, hepatitis B virus core (HBc) particles were used as a carrier of HCV
      epitopes. Fragments of HCV genes encoding core (aa 98) and NS3 (aa 155) proteins
      were fused to the 3' terminus of the truncated HBV core gene. All recombinant
      plasmids led to relatively high levels of expression of chimeric proteins in E.
      coli, which resulted in the formation of complete "mature" VLP. Chimeric HBc/HCV
      VLPs were purified by combination of gel filtration and sucrose gradient
      centrifugation, and used for immunogenicity studies in mice. All variants of
      hybrid particles induced high humoral and cellular responses to HBcAg.
      Immunization with the HBc/HCV core particles led to relatively low antibody and T
      cell proliferative responses to HCV core epitopes. The HBc/HCV NS3 particles were
      able to induce high levels of anti-NS3 antibodies in the absence of proliferative
      responses to HCV epitopes. Thus, the results of the current study have
      demonstrated the principal possibility of using VLP on the basis of HBcAg for
      creation of a new type of HCV-specific immunogen.

PMID- 16574287
TI  - Fractures of the mandible and zygomatic complex: postoperative radiographs are
      not necessary.

PMID- 16574288
TI  - Accumulation of nutrients and heavy metals in Phragmites australis (Cav.) Trin.
      ex Steudel and Bolboschoenus maritimus (L.) Palla in a constructed wetland of the
      Venice lagoon watershed.
AB  - A recently constructed wetland, located in the Venice lagoon watershed, was
      monitored to investigate growth dynamics, nutrient and heavy metal shoot
      accumulation of the two dominating macrophytes: Phragmites australis and
      Bolboschoenus maritimus. Investigations were conducted over a vegetative season
      at three locations with different distance to the inlet point to assess effects
      on vegetation. The distance from the inlet did not affect either shoot biomass or
      nutrients (N, P, K and Na) and heavy metals (Cr, Ni, Cu and Zn) shoot content.
      With the exception of Na, nutrient and heavy metal concentrations were higher in
      shoots of P. australis than in B. maritimus. Heavy metal concentration in the
      incoming water and in the soil was not correlated to the plant content of either
      species. Shoot heavy metal concentrations were similar to those reported in the
      current literature, but accumulation generally increased towards the end of the
      growing season.

PMID- 16574289
TI  - Extending systematic reviews to include evidence on implementation:
      methodological work on a review of community-based initiatives to prevent
      injuries.
AB  - Unintentional injury is a leading cause of mortality and disability among young
      and old. While evidence about the effectiveness of interventions in reducing
      injuries is accumulating, reviews of this evidence frequently fail to include
      details of implementation processes. Our research, of which the work reported
      here formed a part, had two main objectives: (1) to identify evidence about the
      implementation of interventions aimed at reducing unintentional injuries amongst
      children and young people; and (2) to explore methods for systematically
      reviewing evidence on implementation. Existing systematic reviews of the
      effectiveness of interventions aiming to reduce unintentional injuries in
      children and young people formed the starting point for the work reported here.
      In summary, many of the published papers we identified contained little
      information on implementation processes and, even when these were discussed, the
      extent to which authors' claims were based on research evidence was unclear. On
      the basis of the studies we reviewed implementation data were insufficiently
      strong to provide a sound evidence base for practitioners and policymakers.
      Notwithstanding this, we identified valuable data about the context in which such
      initiatives are implemented and the type of factors that might impinge on
      implementation. This work has implications in three areas: (1) researchers with
      an interest in evidence-based public health could be encouraged to consider
      implementation issues in the design of intervention studies; (2) funding bodies
      could be encouraged to prioritise intervention studies using mixed methods that
      will enable researchers to consider effectiveness and implementation; (3) journal
      editors could work towards increasing the quality of reporting on implementation
      issues through the development of guidelines.

PMID- 16574290
TI  - Modelling and understanding primary health care accessibility and utilization in
      rural South Africa: an exploration using a geographical information system.
AB  - Physical access to health care affects a large array of health outcomes, yet
      meaningfully estimating physical access remains elusive in many developing
      country contexts where conventional geographical techniques are often not
      appropriate. We interviewed (and geographically positioned) 23,000 homesteads
      regarding clinic usage in the Hlabisa health sub-district, KwaZulu-Natal, South
      Africa. We used a cost analysis within a geographical information system to
      estimate mean travel time (at any given location) to clinic and to derive the
      clinic catchments. The model takes into account the proportion of people likely
      to be using public transport (as a function of estimated walking time to clinic),
      the quality and distribution of the road network and natural barriers, and was
      calibrated using reported travel times. We used the model to investigate
      differences in rural, urban and peri-urban usage of clinics by homesteads in the
      study area and to quantify the effect of physical access to clinic on usage. We
      were able to predict the reported clinic used with an accuracy of 91%. The median
      travel time to nearest clinic is 81 min and 65% of homesteads travel 1h or more
      to attend the nearest clinic. There was a significant logistic decline in usage
      with increasing travel time (p < 0.0001). The adjusted odds of a homestead within
      30 min of a clinic making use of the clinics were 10 times (adjusted OR = 10; 95
      CI 6.9-14.4) those of a homestead in the 90-120 min zone. The adjusted odds of
      usage of the clinics by urban homesteads were approximately 20/30 times smaller
      than those of their rural/peri-urban counterparts, respectively, after
      controlling for systematic differences in travel time to clinic. The estimated
      median travel time to the district hospital is 170 min. The methodology
      constitutes a framework for modelling physical access to clinics in many
      developing country settings.

PMID- 16574291
TI  - Political and welfare state determinants of infant and child health indicators:
      an analysis of wealthy countries.
AB  - Economic indicators such as income inequality are gaining attention as putative
      determinants of population health. On the other hand, we are just beginning to
      explore the health impact on population health of political and welfare state
      variables such as political orientation of government or type of medical care
      coverage. To determine the socially structured impact of political and welfare
      state variables on low birth weight rate, infant mortality rate, and under-five
      mortality rate, we conducted an ecological study with unbalanced time-series data
      from 19 wealthy OECD countries for the years from 1960 to 1994. Among the
      political/welfare state variables, total public medical coverage was the most
      significant predictor of the mortality outcomes. The low birth weight rate was
      more sensitive to political predictors such as percentage of vote obtained by
      social democratic or labor parties. Overall, political and welfare state
      variables (including indicators of health policies) are associated with infant
      and child health indicators. While a strong medical care system seems crucial to
      some population health outcomes (e.g., the infant mortality rate), other
      population health outcomes might be impacted by social policies enacted by
      parties supporting strong welfare states (the low birth weight rate). Our
      investigation suggests that strong political will that advocates for more
      egalitarian welfare policies, including public medical services, is important in
      maintaining and improving the nation's health.

PMID- 16574292
TI  - Comment on: "Conceptualizing mainstream health care providers' behaviours in
      relation to complementary and alternative medicine" by Hirschkorn and Bourgeault.

PMID- 16574293
TI  - Improvement of tardive dyskinesia following amisulpride treatment.
AB  - Tardive dyskinesia (TD) is a persistent, disturbing side effect of antipsychotic
      drug treatment. It is established that clozapine and other second generation
      agents cause less TD and may also improve pre-existing TD. We report a case of
      significant improvement of TD after the administration of amisulpride, a
      potential D(2)/D(3) antagonist that has atypical properties. The possible effect
      of fast dissociation of D(2) receptors is being discussed.

PMID- 16574294
TI  - Hypersalivation induced by olanzapine with fluvoxamine.
AB  - Hypersalivation has been reported as a side effect of atypical antipsychotics
      such as clozapine and olanzapine. As it is very common for antipsychotics to
      cause dry mouth due to anticholinergic effects, hypersalivation seems to be
      paradoxical. We present the case of a 34-year-old Japanese man with delusional
      disorder, somatic type (DSM-IV). He had chronic neck pain as well as somatic
      hallucination with hypochondriacal delusion for 4 years. Since combination
      therapy with atypical antipsychotics and selective serotonin reuptake inhibitors
      (SSRIs) has been introduced in the treatment of refractory psychiatric disorders
      such as schizophrenia, olanzapine (10 mg/day) was added to fluvoxamine treatment
      (200 mg/day) in this case. Subsequently, hypersalivation was induced without any
      extrapyramidal symptoms. It is suggested that hypersalivation was an adverse
      effect of olanzapine. Possible interaction olanzapine with fluvoxamine might
      increase the risk of the adverse effect. When combination therapy of atypical
      antipsychotics and SSRI is introduced, it should be used cautiously with careful
      observation. Underlying pharmacological and clinical problems will be discussed.

PMID- 16574295
TI  - Tolerance to the antinociceptive effects of ethanol during ethanol withdrawal.
AB  - Prior research has indicated that tolerance develops to the antinociceptive
      effects of ethanol and continues even during withdrawal. Three potential
      pharmacological mechanisms for this tolerance are examined, using nitrendipine (L
      type calcium channel blocker), theophylline (adenosine A1/A2 antagonist) and
      flumazenil (benzodiazepine antagonist). Rats received 10 days of exposure to an
      ethanol-containing liquid diet (6.5% w/v). A radiant heat tail-flick assay was
      used to assess hyperalgesia at 12 h after removal of the liquid diet, as well as
      tolerance to the effects of cumulative doses of ethanol (0.5-2 g/kg). Co
      administration of flumazenil (10 mg/kg, i.p., b.i.d.), nitrendipine (5 mg/kg,
      i.p., b.i.d.) or theophylline (1 mg/kg, i.p., b.i.d.) with chronic ethanol
      prevented development of the hyperalgesia produced by ethanol withdrawal, but
      only theophylline reduced tolerance to the antinociceptive effects of ethanol
      administered during ethanol withdrawal. In contrast, when administered during
      ethanol withdrawal, theophylline (1-10 mg/kg) blocked the anti-hyperalgesic
      effects of ethanol during ethanol withdrawal, whereas nitrendipine (5-25 mg/kg)
      enabled ethanol to produce levels of antinociception comparable to non-dependent
      rats. These findings indicate that L-type calcium channels and adenosine
      receptors play important, but differing roles in the development of hyperalgesia
      during withdrawal, and to tolerance to the antinociceptive effects of ethanol.

PMID- 16574296
TI  - Antioxidative effects of quercetin-glycosides isolated from the flower buds of
      Tussilago farfara L.
AB  - A bioassay-guided fractionation of the ethylacetate soluble fraction from the
      flower buds of Tussilago farfara L. (Compositae) yielded two flavonoids,
      quercetin 3-O-beta-L-arabinopyranoside and quercetin 3-O-beta-D-glucopyranoside.
      These two sugar conjugates of quercetin exhibited higher antioxidative activity
      than their aglycone, quercetin by NBT superoxide scavenging assay. Moreover,
      treatment with quercetin 3-O-beta-L-arabinopyranoside significantly increased the
      total glutathione (GSH) contents and the protein level of gamma-glutamylcysteine
      ligase (gamma-GCL), a key enzyme required for glutathione (GSH) synthesis in a
      rat hepatocyte cell line. Subcellular fractionation and reporter gene analysis
      using antioxidant response element (ARE) construct revealed that quercetin 3-O
      beta-L-arabinopyranoside increased the level of nuclear Nrf2 and reporter
      activity, and that these were associated with the induction of the gamma-GCL
      gene. After 24 h incubation of cells with quercetin 3-O-beta-L-arabinopyranoside,
      23% of the glycoside was converted to its aglycone, quercetin, but gamma-GCL was
      not induced by 7 microM (23%) quercetin. These results suggest that the two
      quercetin-glycosides isolated from T. farfara L. have direct antioxidative
      properties, and that quercetin 3-O-beta-L-arabinopyranoside increases the
      cellular GSH level by inducing the gamma-GCL gene. These novel effects of
      quercetin-glycosides are suggestive to underlie the potential putative
      chemopreventive effects of T. farfara L.

PMID- 16574297
TI  - The role of tumor necrosis factor alpha and the peroxisome proliferator-activated
      receptor alpha in modulating the effects of fumonisin in mouse liver.
AB  - Fumonisins are mycotoxins that are produced by Fusarium verticillioides found in
      corn and corn-based foods, and are suspected human esophageal carcinogens.
      Exposure of rodents to fumonisin B1 causes hepatotoxicity and results in
      alterations in the balance between cell proliferation and apoptosis in the liver.
      As the cytokine tumor necrosis factor alpha (TNFalpha) and the nuclear receptor
      peroxisome proliferator-activated receptor alpha (PPARalpha) also modulate
      hepatocyte proliferation and apoptosis, we tested the hypothesis that fumonisin
      induced hepatotoxicity in the liver is modulated by these factors. We examined
      the effects of dietary exposure to a fumonisin-containing culture material (CM)
      of the fungus F. verticillioides for 8 days or 5 weeks in the livers of mice
      lacking either TNFalpha or PPARalpha. Compared to wild-type mice TNFalpha-null
      mice exhibited increased hepatocyte proliferation and apoptosis. In contrast,
      PPARalpha-null and wild-type mice were found to exhibit similar patterns of
      hepatocyte apoptosis and proliferation when fed the CM diet. Overall, these
      findings provide evidence that TNFalpha, but not PPARalpha, plays a role in
      modulating fumonisin-induced hepatotoxicity in mice.

PMID- 16574299
TI  - Analysis of biomarkers in rats and dogs exposed to polymeric methylenediphenyl
      diisocyanate (pMDI) and its glutathione adduct.
AB  - Hemoglobin adducts (Hb-MDX) of monomeric methylenediphenyl diisocyanate (MDI) are
      often interpreted as indirect evidence of hydrolysis of the diisocyanate moiety
      to the respective amine (diphenylmethane-4,4'-diamine, 4,4'-MDA) which
      constitutes the rationale of using this biomarker as an internal dosimeter of
      exposure to putatively formed MDA. In contrast, more recently published data
      suggest that following inhalation the high concentration of glutathione (GSH)
      present in lungs favor an adduct formation with GSH and/or peptides/proteins
      rather than hydrolysis. The focus of this study was to test this alternate
      hypothesis, viz. whether Hb-MDX can also be formed by the GSH bis-adduct of
      monomeric MDI. The synthesized mMDI-GSH bis-adduct was administered to rats by
      single intratracheal instillation. Additional groups were dosed by gavage and
      intraperitoneal injection. Biomarkers of exposure were determined in blood
      (plasma protein and hemoglobin adducts) and urine after harsh alkaline and acid
      hydrolysis, respectively. Data from previous single inhalation exposure studies
      with aerosols of MDI and 4,4'-MDA in rats served as reference. As to whether N
      acetylation plays any modifying role to yield these mMDI-specific biomarkers was
      addressed in similarly head-only exposed dogs, a species with no appreciable N
      acetylation capacity whereas rats are strong N-acetylators. The results obtained
      suggest that biomarkers in blood from controlled exposures above current
      workplace standards of mMDI appear not to be suitable for reliable assessments of
      past exposures. The biomarkers typically used to assess past exposures to MDI
      were also identified following exposure to the MDI-GSH bis-adduct. Their yield
      was low but quite similar for MDI aerosol and the MDI-GSH bis-adduct, whilst that
      of MDA was distinctively higher. The findings of this study are supportive of a
      conceptual pathway that the MDI-derived biomarkers of exposure are formed through
      MDI-GSH adducts rather than MDA. Data from dogs support the findings from rats
      and show that N-acetylation does not appear to be an essential modifying factor.
      It is concluded that the yield of MDI-related markers of exposure is relatively
      low and dependent on the exposure dose (and route). MDA originating from
      hydrolyzed serum protein or hemoglobin appear to be confounded by false-positive
      background levels which are surmised to be associated with the method of
      hydrolysis. The determination of urinary biomarkers might be a useful tool to
      identify recent exposures (by any route). Due methodological uncertainties
      associated with the harsh hydrolysis of biological specimens may be reduced
      substantially when using incremental pre- to post-shift changes rather than
      relying solely on absolute data.

PMID- 16574300
TI  - New polymeric materials for use in glass-ionomer cements.
AB  - The polymeric materials currently used in GIC are based on poly(acrylic acid),
      poly(acrylic acid-co-itaconic acid), or poly(acrylic acid-co-maleic acid). For
      the visible light cured (VLC) type GIC, the polymeric material is chemically
      modified to have pendant free-radical polymerizable double bonds, with the
      aqueous formulation solution also containing a monomer having methacrylate
      groups. Exploring ways to improve both conventional and VLC GIC, routes to new
      acrylic acid copolymers have been explored, where acid groups are made more
      available for salt-bridge formation. In particular, amino acid modified acrylic
      acid copolymers have been prepared and shown to provide improved GIC. Also, it
      was discovered that the monomer N-vinylpyrrolidone (NVP) could be used to modify
      acrylic acid copolymers to provide a path to improved GIC. A new route to develop
      VLC GIC, based on the reaction of the acid copolymer, in water, with a cyclic
      imino ether (oxazoline) functionalized methacrylate monomer was developed.
      Looking for ways to change the microstructure of the acrylic acid copolymers, as
      a possible route to improve GIC, acrylic acid copolymers have been prepared under
      super critical conditions. A review of the aforesaid areas of research is
      provided in this manuscript.

PMID- 16574301
TI  - Ion processes in glass ionomer cements.
AB  - Ion processes are involved in many aspects of glass-ionomer cements. The ions
      released from the glass take part in the formation of the cement matrix. Although
      this process has been investigated, particularly using model cement systems, no
      study provides a complete matrix composition. Combining results from different
      studies enables an approximate composition to be derived. The importance of
      Phosphorous in controlling ion release from the glass surface has been identified
      in a number of studies. The release of ions from the set cement into water (and
      other aqueous liquids) has been much reported, particularly for fluoride. Over
      most of the release periods studied (i.e. from >7 days up to 3 years), release of
      F ion is related to t1/2 indicating a diffusion-controlled process. Other ions,
      except possibly Na+ also show this relationship. The amount of cumulative F
      release whilst maintaining this relationship indicates that more F than is in the
      matrix is involved. Ion chromatography would probably elucidate the precise form
      of the ionic species released. Glass-ionomer cements take up ions from solutions
      in which they are immersed. The levels are much higher than required to produce
      as internal/external equilibrium. Studies using dynamic SIMS and XPS give some
      information on ion location and elemental association. It is suggested that ToF
      SIMS would elucidate these further. Re-release of uptaken ions can vary
      considerably for different cements and ion species. Surface disruption of glass
      ionomers is caused by both F ion and monofluorophosphate ion and occurs much more
      readily in F containing cements than in F free ones. The mechanism of this
      process has not been elucidated. Analysis of the ions released from the cement as
      disruption occurs should provide an indication of the site of attack.

PMID- 16574302
TI  - They know the words, but not the music: affective and semantic priming in
      individuals with psychopathy.
AB  - Previous work has indicated dysfunctional affect-language interactions in
      individuals with psychopathy through use of the lexical decision task. However,
      it has been uncertain as to whether these deficits actually reflect impaired
      affect-language interactions or a more fundamental deficit in general semantic
      processing. In this study, we examined affective priming and semantic priming
      (dependent measures were reaction times and error rates) in individuals with
      psychopathy and comparison individuals, classified according to the psychopathy
      checklist revised (PCL-R) [Hare, R.D., 1991. The Hare Psychopathy Checklist
      Revised. Multi-Health Systems, Toronto, Ont] Individuals with psychopathy showed
      significantly less affective priming relative to comparison individuals. In
      contrast, the two groups showed comparable levels of semantic priming. The
      results are discussed with reference to current models of psychopathy.

PMID- 16574303
TI  - Staff views on the management of the extremely preterm infant.
AB  - OBJECTIVE: To explore the opinions of different healthcare professionals about
      the use of interventions and outcome in extremely preterm labour. STUDY DESIGN:
      This was a prospective questionnaire survey. A structured questionnaire was
      mailed to 142 obstetricians, neonatologists, midwives and neonatal nurses working
      at City Hospital and Queen's Medical Centre, Nottingham, UK. The current opinions
      of practice of the healthcare professionals in their antenatal and intrapartum
      management of a woman with an extremely preterm infant were sought. RESULTS: The
      overall response was 49% (n=69) after two mailings. Most respondents
      overestimated infant survival and underestimated intact infant survival rates.
      Neonatal staff were most likely to wish to use electronic fetal monitoring and
      administer corticosteroids at the lower extreme gestations. There was no
      consensus on when to use corticosteroids. Consultant obstetricians were expected
      to be responsible for counselling parents before delivery, when time allows, but
      their presence at delivery was not thought to be essential. Neonatal nurses would
      recommend in utero transfer for women more readily at lower gestations whereas
      midwives were more reluctant to accept these women as in utero transfers. There
      were no significant differences in the attitudes to resuscitation of the
      extremely preterm infant among the different professionals. The median
      birthweights at which active resuscitation should be commenced ranged from 400 g
      for neonatal nurses to 500 g for midwives. CONCLUSIONS: Different professional
      groups perceive outcome differently and this may affect willingness to use
      interventions at borderline viability. Generally, neonatal staff wished to be
      more interventional at 21-23 weeks of gestation.

PMID- 16574304
TI  - Improvement of uterine artery Doppler velocimetry indices after metroplasty in
      arcuate uteri.
AB  - OBJECTIVE: Our study aimed to evaluate the effect of metroplasty performed in
      arcuate uteri on uterine artery Doppler velocimetry. STUDY DESIGN: We performed
      uterine artery Doppler velocimetry transvaginally before and after metroplasty in
      36 women with arcuate uteri. Pulsatility indexes (PI) of uterine arteries were
      calculated and the presence or absence of a protodiastolic notch was evaluated.
      RESULTS: Comparing Doppler indexes before and after metroplasty, we found that
      uterine artery impedance improves as assessed by lower mean PI. We observed that
      PI after intervention was significantly lower compared with indexes before for
      mean Doppler index evaluations (mean uterine PI pre: 2.07+/-0.61 and post: 1.49+/
      0.24 [p<0.03]). No differences were observed as regards bilateral protodiastolic
      notch absence or presence. A protodiastolic notch was present in 22 out of 36
      women before metroplasty (61%), and a notch was observed in 19 out of 36 (52%)
      after metroplasty. CONCLUSIONS: Our results suggest that, metroplasty, as well as
      making the uterine cavity wider, leads to better uterine perfusion.

PMID- 16574305
TI  - Effects of warm water inflows on the dispersion of pollutants in small
      reservoirs.
AB  - The effects of the warm water discharged by a nuclear power plant (NPP) into a
      small reservoir are studied. A case study is presented (Jose Cabrera NPP-Zorita
      Hidraulica Reservoir) with experimental data of the reservoir stratification and
      predicted data of the dispersion of radioactive pollutants from operative or
      accidental releases. The vertical and longitudinal temperature profiles,
      electrical conductivity and transparency of the reservoir water were measured for
      an annual cycle. The results indicate that the continuous warm water discharge
      from the NPP causes permanent and artificial reservoir stratification. The
      stratification is significant within 1500 m upstream and 1000 m downstream from
      the warm water outfall. The pollutant dispersion has been predicted by using a
      flow model based on N(T) perfect-mixing compartments in series with feedback. The
      model parameter, N(T), is calculated from the longitudinal diffusion coefficient.
      The prediction of pollutant dispersion by means of this model shows that the
      stratification slows down the vertical mixing in the whole water body, and
      reduces the reservoir volume that is effective for the dilution and dispersion of
      pollutants. This means that, in the case of a radioactive pollutant release, the
      reservoir radioactivity level could increase significantly.

PMID- 16574306
TI  - Landscape ecological assessment: a tool for integrating biodiversity issues in
      strategic environmental assessment and planning.
AB  - To achieve a sustainable development, impacts on biodiversity of urbanisation,
      new infrastructure projects and other land use changes must be considered on
      landscape and regional scales. This requires that important decisions are made
      after a systematic evaluation of environmental impacts. Landscape ecology can
      provide a conceptual framework for the assessment of consequences of long-term
      development processes like urbanisation on biodiversity components, and for
      evaluating and visualising the impacts of alternative planning scenarios. The aim
      of this paper was to develop methods for integrating biodiversity issues in
      planning and strategic environmental assessment in an urbanising environment, on
      landscape and regional levels. In order to test developed methods, a case study
      was conducted in the region of Stockholm, the capital of Sweden, and the study
      area embraced the city centre, suburbs and peri-urban areas. Focal species were
      tested as indicators of habitat quality, quantity and connectivity in the
      landscape. Predictive modelling of habitat distribution in geographic information
      systems involved the modelling of focal species occurrences based on empirical
      data, incorporated in a landscape ecological decision support system. When
      habitat models were retrieved, they were applied on future planning scenarios in
      order to predict and assess the impacts on focal species. The scenario involving
      a diffuse exploitation pattern had the greatest negative impacts on the habitat
      networks of focal species. The scenarios with concentrated exploitation also had
      negative impacts, although they were possible to mitigate quite easily. The
      predictions of the impacts on habitats networks of focal species made it possible
      to quantify, integrate and visualise the effects of urbanisation scenarios on
      aspects of biodiversity on a landscape level.

PMID- 16574307
TI  - Study of urban population attitudes towards various wastewater reuse options:
      Israel as a case study.
AB  - This paper summarizes the findings of a survey (256 participants) conducted to
      determine the attitude of the Israeli urban public towards various urban water
      reuse options. Israel is known for its long and successful agricultural water
      reuse scheme, but to date no large-scale urban reuse projects have been
      implemented. The survey included 21 reuse options, which were clustered into
      three reuse categories, namely: low, medium, and high contact levels. Results
      show that a high proportion of the participants supported medium contact reuse
      options such as sidewalk landscaping (95%), domestic WC flushing (85%) and
      firefighting (96%). Higher contact reuse options such as domestic laundry (38%),
      preserved food (13%), and potable aquifer recharge (11%) found much lesser
      support. Less than expected support was found for low contact reuse options with
      86% for field crop irrigation, 62% for aquifer recharge for agricultural
      irrigation, and as low as 49% for orchard irrigation. This low support is
      surprising, since all three options have been practiced on a large scale for over
      three decades in Israel without any adverse effects to the public. No correlation
      was found between any biographical characteristic examined (education, gender,
      income, marital status, having young children, and age) and support for medium
      contact options. For the medium contact options, the results suggest that
      perceived financial gain (individual and/or communal) and positive public opinion
      enhances support, while perceived health effects negatively affects the degree of
      support. Technology, trust in authorities and awareness of water and
      environmental issues were found to not have a significant effect on support for
      medium contact reuse options. Analyzing the four possible reasons for support
      given by participants who identified themselves as supporters of wastewater reuse
      revealed that the most important reason for support was "water saving", followed
      by "minimization of importing water from abroad". These were followed by
      "infrastructure cost saving" together with "environmental improvement".

PMID- 16574308
TI  - An assessment of Spain's Programa AGUA and its implications for sustainable water
      management in the province of Almeria, southeast Spain.
AB  - Spain's Programa AGUA was proposed in 2004 as a replacement for the Spanish
      National Hydrological Plan and represented a fundamental policy shift in national
      water management from large inter-basin water transfers to a commitment to
      desalination. Twenty-one desalination facilities are planned for six provinces on
      the Spanish Mediterranean coast to supplement their water needs. These include
      the province of Almeria that for the last 30 years has endured a net water
      abstraction overdraft leading to serious reservoir depletion and groundwater
      imbalances. Rising water use is a result of increasing demand to support
      irrigated agriculture (e.g. greenhouse horticulture) and for domestic needs (e.g.
      rapid urban growth and tourism development), which has led observers to question
      Almeria's long-term water sustainability. Desalinated water alone is unlikely to
      be sufficient to make up these water deficits and water-users will have to accept
      a move to full-price water recovery by 2010 under the European Union (EU) Water
      Framework Directive of which Spain is a signatory. Anticipated water efficiencies
      resulting from higher water tariffs, increasing water reuse and water
      infrastructure improvements (including inter-basin transfers), in conjunction
      with increasing use of desalinated water, are expected to address the province's
      current water overdraft. However, Almeria will need to balance its planned
      initiatives against long-term estimates of projected agricultural and domestic
      development and the environmental consequences of adopting a desalination
      supported water future.

PMID- 16574309
TI  - An integrated fuzzy-stochastic modeling approach for risk assessment of
      groundwater contamination.
AB  - An integrated fuzzy-stochastic risk assessment (IFSRA) approach was developed in
      this study to systematically quantify both probabilistic and fuzzy uncertainties
      associated with site conditions, environmental guidelines, and health impact
      criteria. The contaminant concentrations in groundwater predicted from a
      numerical model were associated with probabilistic uncertainties due to the
      randomness in modeling input parameters, while the consequences of contaminant
      concentrations violating relevant environmental quality guidelines and health
      evaluation criteria were linked with fuzzy uncertainties. The contaminant of
      interest in this study was xylene. The environmental quality guideline was
      divided into three different strictness categories: "loose", "medium" and
      "strict". The environmental-guideline-based risk (ER) and health risk (HR) due to
      xylene ingestion were systematically examined to obtain the general risk levels
      through a fuzzy rule base. The ER and HR risk levels were divided into five
      categories of "low", "low-to-medium", "medium", "medium-to-high" and "high",
      respectively. The general risk levels included six categories ranging from "low"
      to "very high". The fuzzy membership functions of the related fuzzy events and
      the fuzzy rule base were established based on a questionnaire survey. Thus the
      IFSRA integrated fuzzy logic, expert involvement, and stochastic simulation
      within a general framework. The robustness of the modeling processes was enhanced
      through the effective reflection of the two types of uncertainties as compared
      with the conventional risk assessment approaches. The developed IFSRA was applied
      to a petroleum-contaminated groundwater system in western Canada. Three scenarios
      with different environmental quality guidelines were analyzed, and reasonable
      results were obtained. The risk assessment approach developed in this study
      offers a unique tool for systematically quantifying various uncertainties in
      contaminated site management, and it also provides more realistic support for
      remediation-related decisions.

PMID- 16574310
TI  - Corticosteroids and tamsulosin in the medical expulsive therapy for symptomatic
      distal ureter stones: single drug or association?
AB  - OBJECTIVES: To assess the clinical role of corticosteroids in the medical
      expulsive therapy of symptomatic distal ureteral stones. METHODS: Between January
      2004 and September 2005, 114 patients with symptomatic distal ureteral stones
      with a >/=5mm diameter were enrolled in this prospective study and divided into
      four groups based on the urologist (of four) who treated them in the emergency
      unit. Group A (33 patients) received tamsulosin (0.4mg daily), group B (24
      patients) received deflazacort (30mg daily), group C (33 patients) received both
      (0.4mg tamsulosin+30mg deflazacort daily), and control group D (24 patients)
      received only analgesics. The treatment duration was 10 d to prevent the side
      effects of prolonged corticosteroid therapy. The end points were the expulsion
      rate, analgesic consumption, number of ureteroscopies, and safety. RESULTS: The
      groups were comparable in terms of age, sex, and stone location. The stone
      diameter was 5.96+/-0.33mm for group A, 5.83+/-0.4mm for group B, 5.88+/-0.23mm
      for group C, and 5.71+/-0.5mm (p>0.05) for group D. The rates of expulsion for
      the four groups were 60%, 37.5%, 84.8%, and 33.3%, respectively. There was a
      significant difference between group C and the other groups (p<0.001). The mean
      analgesic consumption was 42.5+/-0.4mg for group A, 50+/-0.3mg for group B,
      27.3+/-0.5mg for group C, and 81+/-0.33mg for group D, with a significant
      difference between group C and the other groups (p<0.001). During the treatment
      period, only two cases of drug side-effects related to tamsulosin (without any
      drop-outs) were recorded. CONCLUSION: When the medical expulsive therapy for
      symptomatic distal ureteral stones is considered, the use of steroids
      (deflazacort) proves efficient only when administered together with alpha(1)
      blockers (tamsulosin). In addition, tamsulosin used on its own as a medical
      expulsive therapy can be considered as an alternative treatment for those
      patients who are not suitable for steroid therapy, as it is generally efficient.

PMID- 16574311
TI  - RS5444, a novel PPARgamma agonist, regulates aspects of the differentiated
      phenotype in nontransformed intestinal epithelial cells.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is expressed in the
      intestinal epithelium, yet little is known about the physiological role of
      PPARgamma in the small bowel or the effects of PPARgamma on small intestinal
      epithelial cells. The present studies investigate cellular and genomic effects of
      PPARgamma in nontransformed rat intestinal epithelial cells (RIE). These cells
      were engineered to express mouse PPARgamma1, and thereby to model the molecular
      phenotype that obtains upon induction of PPARgamma at the crypt/villus junction
      in the small intestine. In these studies, we have used a novel third generation
      thiazolidinedione derivative, RS5444, which activates PPARgamma with an EC50
      about 1/50th that of rosiglitazone and has no effect on RIE cells that do not
      express PPARgamma. We used Affymetrix oligonucleotide microarrays to identify
      potential PPARgamma-regulated processes in RIE cells, including lipid metabolism,
      cell proliferation and differentiation, remodeling of the extracellular matrix,
      cell morphology, cell-cell adhesion, and motility. The genomic profile reflects
      cellular events that occur following PPARgamma activation: RS5444 inhibited
      culture growth and caused irreversible G1 arrest, but did not induce apoptosis.
      In addition, RS5444 caused dramatic changes in cellular morphology which were
      associated with increased motility and diminished cellular adherence, but no
      increase in the ability of such cells to digest and invade Matrigel. Inhibition
      of proliferation, cell cycle arrest, increased motility, and altered adherence
      are aspects of the differentiated phenotype of villus epithelial cells, which
      withdraw from the cell cycle at the crypt/villus interface, migrate to the villus
      tips, and are subsequently shed by loss of contact with the epithelium and the
      underlying extracellular matrix. Our results are consistent with the hypothesis
      that PPARgamma regulates critical aspects of differentiation in the small
      intestinal epithelium. Many nuclear receptors regulate differentiation. However,
      our results point to novel effects of PPARgamma on cell-cell and cell-matrix
      interactions, which are not typical of other nuclear receptors.

PMID- 16574312
TI  - Pbx1 is a co-factor for Cdx-2 in regulating proglucagon gene expression in
      pancreatic A cells.
AB  - A number of Hox and Hox-like homeodomain (HD) proteins have been previously shown
      to utilize members of the TALE HD protein family as co-factors in regulating gene
      expression. The caudal HD protein Cdx-2 is a transactivator for the proglucagon
      gene, expressed in pancreatic A cells and intestinal endocrine L cells. We
      demonstrate here that co-transfection of the TALE homeobox gene Pbx1 enhanced the
      activation of Cdx-2 on the proglucagon promoter in either the pancreatic A cell
      line InR1-G9 or BHK fibroblasts. The activation was observed for proglucagon
      promoter constructs with or without the binding motifs for Pbx1. Furthermore,
      mutating the penta-peptide motif (binding motif for TALE HD proteins) on Cdx-2
      substantially attenuated its activation on proglucagon promoter, but not on the
      sucrase-isomaltase gene (SI) promoter, or its own (Cdx-2) promoter; suggesting
      that Cdx-2 utilizes Pbx1 as a co-factor for regulating the expression of selected
      target genes. Physical interaction between Cdx-2 and Pbx1 was demonstrated by co
      immunoprecipitation as well as GST fusion protein pull-down. We suggest that this
      study reveals a novel function for Pbx1 in pancreatic islet physiology:
      regulating proglucagon expression by serving as a co-factor for Cdx-2.

PMID- 16574313
TI  - Myocardial antioxidant enzyme activities and concentration and glutathione
      metabolism in experimental hyperthyroidism.
AB  - Hyperthyroidism was induced in rats by l-thyroxine administration (12 mg/L in
      drinking water, 4 weeks). Animals were assessed hemodynamically, and heart, lung,
      and liver morphometry were performed. Lipid peroxidation (LPO) and protein
      oxidation (carbonyls) were measured in heart homogenates. It was quantified
      glutathione (GSH) metabolism, and antioxidant enzyme activities its and protein
      expression (by Western blot). At the end of treatment, it was observed cardiac
      hypertrophy, elevation of left ventricular systolic and end diastolic pressures,
      lung and liver congestion. LPO and carbonyls were increased in the hyperthyroid
      group, and GSH was decreased by 46% in the fourth week. Myocardial oxidative
      stress time course analysis revealed that it was increased in the second week of
      treatment. Antioxidant enzyme activities elevation was accompanied by protein
      expression induction in the hyperthyroid group in the fourth week. These results
      imply that hyperthyroidism generates myocardial dysfunction associated with
      oxidative stress inducing antioxidant enzyme activities and protein expression.

PMID- 16574314
TI  - The pleiotropic function of PPAR gamma in the placenta.
AB  - At different stages of placental development the cytotrophoblasts differentiate
      into specialized cells that are vital for specific placental tasks. These types
      include the invasive trophoblasts, which are responsible for invasion of the
      placenta into the uterine wall, and syncytiotrophoblasts, which form a barrier
      between the maternal and fetal circulations, govern trans-placental transport of
      gas, nutrient and waste, and produce placental hormones. Recent research
      illuminated the role of the nuclear receptor peroxisome proliferator-activated
      receptor-gamma (PPAR gamma) in the areas of adipocyte and macrophage biology,
      insulin action, bioenergetics and inflammation. It was somewhat surprising that
      PPAR gamma was also found to play a pivotal role in placental biology. In this
      review we summarize recent data, which show that PPAR gamma is expressed in the
      placenta, particularly in trophoblasts, and is essential for placental
      development, trophoblast invasion, differentiation of cytotrophoblasts into
      syncytium, and regulation of fat accumulation in trophoblasts. PPAR gamma may
      also play a role in modulating fetal membrane signals toward parturition. The
      data presented here underscore the need for a focused investigation of the unique
      aspects of PPAR gamma function in trophoblasts, which may have direct
      implications for the use of PPAR gamma ligands during pregnancy.

PMID- 16574315
TI  - Pyruvate dehydrogenase phosphatase deficiency: orphan disease or an under
      diagnosed condition?
AB  - Pyruvate dehydrogenase phosphatase (PDP) is an enzyme which regulates the
      activity of the pyruvate dehydrogenase complex (PDHc). In the past, PDHc
      deficiency has been attributed to mutations in the complex itself and the
      regulatory enzymes have not been considered. We have recently reported the first
      mutation in PDP1, one of the two isoforms of PDP, which results in severe
      exercise intolerance and mild developmental delay in patients. This novel process
      of aberrant pyruvate metabolism opens up a new avenue for investigation into PDHc
      deficiency, that has hitherto been underappreciated.

PMID- 16574316
TI  - Immunohistochemical demonstration of proliferating lymphatic vessels in
      colorectal carcinoma and its clinicopathological significance.
AB  - Lymphatic metastasis to the regional lymph nodes through the lymphatic vessels is
      an important indicator of poor prognosis in many types of malignant tumors.
      Recently, much attention has been paid to lymphangiogenesis for its possible role
      on tumor progression in various carcinomas. However, morphological evidence that
      lymphatic vessels actively proliferate in colorectal carcinoma has not been
      reported. Here, we first devised a triple immunostaining method to detect
      proliferating lymphatic vessels utilizing antibody to Ki-67 antigen as a marker
      of cell proliferation, antibody to cytokeratin as an epithelial cell marker, and
      antibody to podoplanin as a lymphatic vessel-specific marker. Ki-67/podoplanin
      immunoreactivity enabled us to identify proliferating lymphatic vessels, while
      cytokeratin immunoreactivity allowed us to distinguish proliferating lymphatic
      vessels from Ki-67/cytokeratin-positive carcinoma cells in lymphatic lumens.
      Analyzing 64 colorectal carcinoma patients' samples using this technique, we
      showed that both lymphatic vessel density and proliferating activity of lymphatic
      vessels were significantly increased in colorectal carcinoma tissues compared
      with their normal counterparts. We then examined the correlation between the
      degree of lymphangiogenesis and patients' prognosis or clinicopathological
      variables, but no statistically significant differences were obtained in these
      analyses. Thus, these results combined together indicate that extensive
      lymphangiogenesis occurs in colorectal carcinoma, but that the degree of
      lymphangiogenesis alone is not an independent prognostic factor for this disease.

PMID- 16574317
TI  - Distinct roles for RB loss on cell cycle control, cisplatin response, and
      immortalization in Schwann cells.
AB  - Schwann cells play a critical role in peripheral nerve function. Regulated
      proliferation of Schwann cells is an important facet of the response to nerve
      injury; however, aberrant proliferation can give rise to Schwann cell tumors such
      as malignant peripheral nerve sheath tumors (MPNST). These tumors exhibit a range
      of genetic lesions that include loss of the retinoblastoma tumor suppressor (RB)
      pathway. RB plays a critical role in the regulation of cellular proliferation and
      its loss is a common event in human cancers. Here, the specific action of RB loss
      on Schwann cell proliferation and response to therapeutic intervention was
      explored. In primary mouse Schwann cells, conditional RB loss led to increased
      levels of critical cell cycle regulatory gene products, yet provided only a
      modest influence on proliferation. However, RB-deficient Schwann cells
      efficiently bypassed the cell cycle inhibitory response to the chemotherapeutic
      agent cisplatin, which is used in the treatment of MPNST and other glial tumors.
      Surprisingly, RB loss did not facilitate Schwann cell immortalization; and RB
      deficient cells actually were less prone to immortalization than cells containing
      RB. Furthermore, RB-deficient cells that ultimately re-entered the cell cycle had
      lost both Schwann cell morphology and markers. Since, RB loss is likely a late
      event in Schwann cell tumor progression, the action of acute RB loss in
      immortalized Schwann cells was investigated. In this context, loss of RB had a
      profound effect on expression of target genes and the response to cisplatin.
      Thus, the loss of RB in both primary and immortal Schwann cells disrupted the
      response to anti-mitogenic signals and has implications for therapeutic
      intervention.

PMID- 16574318
TI  - Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase.
      Implications for increasing its ability to inhibit the growth of sensitive and
      multidrug resistant leukaemia HL60 cells.
AB  - The aim of this study was to examine the role of reductive activation of
      mitoxantrone (MX) by human liver NADPH cytochrome P450 reductase (CPR) in
      increasing its ability to inhibit the growth of human promyelocytic sensitive
      leukaemia HL60 cell line as well as its MDR sublines exhibiting two different
      phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or
      MRP1 (HL60/DOX). Our assays showed that the reduction of MX by exogenously added
      CPR in the presence of low NADPH concentration had no effect in increasing its
      ability to inhibit the growth of sensitive and MDR tumour cells. In contrast, an
      important increase in antiproliferative activity of MX after its reductive
      activation by CPR at high NADPH concentration was observed against HL60/VINC as
      well as HL60/DOX cells.

PMID- 16574320
TI  - Adsorption of phenolic compound by aged-refuse.
AB  - The adsorption of phenol, 2-chlorophenol, 4-chlorophenol and 2,4-dichlorophenol
      by aged-refuse has been studied. Adsorption isotherms have been determined for
      phenol, 2-chlorophenol, 4-chlorophenol and 2,4-dichlorophenol and the data fits
      well to the Freundlich equation. The chlorinated phenols are absorbed more
      strongly than the phenol and the adsorption capacity has an oblivious
      relationship with the numbers and the position of chlorine subsistent. The
      experiment data suggests that both the partition function and the chemical
      adsorption involve in the adsorption process. Pseudo-first-order and pseudo
      second-order model were applied to investigate the kinetics of the adsorption and
      the results show that it fit the pseudo-second-order model. More than one step
      involves in the adsorption process and the overall rate of the adsorption process
      appears to be controlled by the chemical reaction. The thermodynamic analysis
      indicates that the adsorption is spontaneous and endothermic.

PMID- 16574319
TI  - Enhanced induction of mitochondrial damage and apoptosis in human leukemia HL-60
      cells by the Ganoderma lucidum and Duchesnea chrysantha extracts.
AB  - Combined treatment with the medicinal mushroom Ganoderma lucidum and the herb
      Duchesnea chrysantha extracts (GDE) causes a synergistic induction of
      mitochondrial damage and apoptosis in HL-60 cells. GDE treatment is selectively
      toxic to HL-60 leukemia cells whereas no cytotoxic effect is observed in normal
      peripheral blood mononuclear cells. GDE-induced apoptosis is associated with Bcl
      2 down-regulation, Bax translocation, mitochondrial cytochrome c release and
      caspase-3 activation, suggesting that apoptosis by this combination occurs
      through the mitochondria-dependent pathway. The present findings suggest that
      this combination merits further investigation as a potential therapeutic agent
      for the treatment of cancer.

PMID- 16574321
TI  - Postural reactions to soleus muscle vibration in Parkinson's disease: scaling
      deteriorates as disease progresses.
AB  - Previous research has shown that Parkinson's disease (PD) patients, especially
      those with postural instability, respond hyperactively to visual, vestibular, and
      neck proprioceptive sensory manipulation. To determine if this impairment of the
      sensory information scaling holds true for the lower leg proprioceptive system,
      we studied postural responses to mechanical vibration (which affects the muscle
      spindle Ia afferents) applied to the soleus muscles of PD subjects and healthy
      controls. Early-stage and advanced-stage PD patients as well as age-matched
      control subjects participated. Each group comprised 11 subjects. Nine pulses of 3
      s long vibration were applied randomly to both soleus muscles while subjects kept
      their eyes closed. Postural responses to these stimuli were measured by static
      posturography. The effect of dopaminergic medication was established by testing
      patients in both ON and OFF treatment phases. There was no intergroup difference
      in the pattern or latencies of responses. However, the amplitudes were
      significantly larger in advanced PD patients; controls did not differ from early
      stage PD patients. Dopaminergic medication had no significant effect on any of
      the measures. The scaling of postural reactions triggered by lower leg
      proprioception is disturbed in advanced PD. Neither afferent proprioceptive
      deficits nor inaccurate timing is involved. This study gives further evidence for
      the generalized impairment of the scaling of postural responses evoked whenever
      there is a sudden change of sensory conditions, as occurs with the progression of
      PD. Such impairment could play a significant role in the pathophysiology of
      postural instability and falls in PD patients.

PMID- 16574322
TI  - Polymorphisms in the phosphate and tensin homolog gene are not associated with
      late-onset Alzheimer's disease.
AB  - The varepsilon4 allele of the APOE locus is the only confirmed risk factor for
      late-onset Alzheimer's disease (LOAD). The phosphate and tensin homolog (PTEN)
      gene is both a biological and positional candidate gene for LOAD. Eight
      polymorphisms spanning this gene were selected from dbSNP and genotyped in pooled
      DNA samples of both cases and controls. No evidence for association with LOAD was
      obtained in this study although further investigation revealed low levels of
      linkage disequlibrium (LD) between the genotyped SNPs. Our results suggest that
      it is unlikely that genetic variation within the PTEN gene contributes to risk of
      LOAD.

PMID- 16574323
TI  - Facilitation of glutamatergic synaptic transmission in hippocampal CA1 area of
      rats with traumatic brain injury.
AB  - We investigated the effects of traumatic brain injury (TBI) on the glutamatergic
      synaptic transmission in the hippocampal CA1 area. A moderate impact (3.8-4.8atm)
      was applied onto the left parietal cerebral cortex by a fluid percussion injury
      (FPI) device. Conventional intracellular recordings were made from hippocampal
      CA1 pyramidal neurons in vitro. Electrophysiological properties of these neurons
      were compared between three groups (control, FPI-ipsilateral, and FPI
      contralateral). The excitability of postsynaptic membrane of CA1 pyramidal
      neurons was not altered by the moderate FPI; however, the evoked glutamatergic
      excitatory synaptic transmission in the pyramidal neurons of post-FPI-CA1 was
      enhanced. Paired-pulse facilitation (PPF) was significantly suppressed in both
      the FPI-ipsilateral and FPI-contralateral groups and the frequencies of mEPSPs in
      neurons from the bilateral FPI groups were greater than the frequency in the
      control group. These results suggest that the glutamatergic synaptic transmission
      in the hipppocampal CA1 area is facilitated through presynaptic mechanisms after
      TBI.

PMID- 16574324
TI  - Evaluation of multiple low doses of copper oxide wire particles compared with
      levamisole for control of Haemonchus contortus in lambs.
AB  - High levels of anthelmintic resistance in gastrointestinal nematodes (GIN) of
      small ruminants have created the need for alternative approaches to parasite
      control. Copper oxide wire particles (COWP; 2g) have proven effective in
      decreasing GIN infection in lambs. However, the risk of copper toxicity has
      limited the usefulness of this approach. Recently, smaller doses (0.5 and 1g)
      have proven effective in GIN control, reducing the risk of toxicity. The
      objective of this study was to examine the effectiveness and risk of toxicity
      using multiple small doses of COWP for GIN control in lambs between weaning and
      market weight. Dorper crossbred ram lambs were orally administered levamisole
      (Levasol, 8.0mg/kg; n=8), 0.5g (n=9), or 1g COWP (n=9) at weaning (Day 0; 118+/-2
      days of age; late May 2005) and again at 6-week intervals for a total of four
      treatments. A pooled fecal culture determined that Haemonchus contortus was the
      predominant gastrointestinal parasite at weaning. Lambs grazed bermudagrass
      pastures and were supplemented with up to 500g corn/soybean meal and free choice
      trace mineralized salt. Fecal egg counts (FEC), packed cell volume (PCV), and
      plasma aspartate aminotransferase (AST) activity were determined every 14 days
      and lambs weighed every 28 days. GIN infection reached a peak at Day 42 (high
      FEC, low PCV). COWP effectively reduced FEC on Days 0 and 42 compared with the
      previous week, but did not reduce FEC on Days 84 and 126 (treatment by time
      interaction, P<0.005). Plasma AST activity and weight gains were similar among
      treatment groups throughout the study period. Concentrations of copper in the
      liver on Day 155 were greater in COWP-treated lambs (P<0.001), but all
      concentrations were normal. Multiple doses of COWP were as effective as
      levamisole for control of H. contortus without risk of copper toxicity.

PMID- 16574325
TI  - Trypanosomosis prevalence in cattle on Mafia Island (Tanzania).
AB  - During two consecutive surveys (February and August/Sept 2002), a total of 970
      cattle from the cattle population of Mafia Island (United Republic of Tanzania)
      were blood-sampled. All blood samples were microscopically screened for the
      presence of trypanosomes and a portion of these were checked for antibodies with
      an Ab-ELISA and for the presence of trypanosomal DNA with PCR. Microscopic
      evidence of trypanosomes of the congolense group (sub-genus Nannomonas) was found
      in 0.8% of the animals (8/970) and in two cases the species identified was
      confirmed by PCR as Trypanosoma congolense savannah type. Non-pathogenic
      Trypanosoma theileri were detected in 3.2% (31/970) of the samples using the Dark
      Ground-Buffy Coat (DG-BC) technique. For survey 1 (S1), detection of antibodies
      (Ab-ELISA) against pathogenic trypanosomes indicated a seroprevalence of 14.2%
      (68/480). Of the samples, either DG positive or with a PCV lower then 25,
      examined by PCR, a total of 8.4% (5/59) (selected from 970 samples), were found
      positive for T. congolense. The low prevalence of pathogenic trypanosomes on
      Mafia Island is intriguing, especially in view of the omnipresence of the tsetse
      fly Glossina brevipalpis. Although the presence of detected trypanosomal
      antibodies does not necessarily indicate a current infection, the combination of
      serological/parasitological examinations and the results of the PCR do support
      this low prevalence of trypanosomosis in cattle. Despite the low prevalence,
      pathogenic trypanosomes are present on Mafia Island and possible reasons for this
      low infection rate, taking account of the relation between Glossina species
      present, transmission risk and trypanosomes found in cattle, are discussed also
      in view of a future appropriate intervention strategy.

PMID- 16574326
TI  - Identification of a protein disulfide isomerase of Neospora caninum in excretory
      secretory products and its IgA binding and enzymatic activities.
AB  - A protein disulfide isomerase of Neospora caninum (NcPDI) with a molecular weight
      of 50kDa was identified in tachyzoite lysate and excretory-secretory (ES)
      products. The IgA antibody in 58.0% of the individual cattle tear samples
      recognized the NcPDI, which suggests that the PDI-specific antibody may be
      involved in defense against parasites. In addition, PDI-specific inhibitors and
      NcPDI antiserum showed inhibitory effects on the growth of N. caninum
      tachyzoites. Furthermore, the purified recombinant NcPDI demonstrated biological
      activities in vitro by catalysis and refolding of reduced RNase A and assisted in
      the recovery of native lysozyme. These findings indicate that NcPDI possesses PDI
      specific enzymatic activity and could be a putative target for chemotherapy for
      neosporosis.

PMID- 16574328
TI  - A carboxylesterase from the thermoacidophilic archaeon Sulfolobus solfataricus
      P1; purification, characterization, and expression.
AB  - The carboxylesterase, a 34 kDa monomeric enzyme, was purified from the
      thermoacidophilic archaeon Sulfolobus solfataricus P1. The optimum temperature
      and pH were 85 degrees C and 8.0, respectively. The enzyme showed remarkable
      thermostability: 41% of its activity remained after 5 days of incubation at 80
      degrees C. In addition, the purified enzyme exhibited stability against
      denaturing agents, including various detergents, urea, and organic solvents. The
      enzyme has broad substrate specificity towards various PNP esters and short acyl
      chain triacylglycerols such as tributyrin (C4:0). Among the PNP esters tested,
      the best substrate was PNP-caprylate (C8) with Km and kcat values of 71 microM
      and 14,700 s(-1), respectively. The carboxylesterase gene consisted of 915 bp
      corresponding to 305 amino acid residues. We demonstrated that active recombinant
      S. solfataricus carboxylesterase could be expressed in Escherichia coli. The
      enzyme was identified as a serine esterase belonging to mammalian hormone
      sensitive lipases (HSL) family and contained a catalytic triad composed of
      serine, histidine, and aspartic acid in the active site.

PMID- 16574327
TI  - Cartilage aggrecan undergoes significant compositional and structural alterations
      during laryngeal cancer.
AB  - Aggrecan is a key component of cartilage and is responsible for the integrity and
      function of the tissue. In this study, the content of aggrecan and its structural
      modifications in adjacent to cancer apparently normal cartilages (AANCs) from
      various stages of laryngeal squamous cell carcinoma (LSCC) were investigated. Our
      data demonstrated a stage-related loss of aggregable aggrecan in AANCs, compared
      to the healthy laryngeal cartilage (HLC), which was excessive in advanced stages
      of disease. On aggregable aggrecan level, AANCs were characterized by significant
      compositional and structural modifications, the extent of which was closely
      related with the stage of LSCC. Four concrete subpopulations of aggregable
      molecules with particular physicochemical characteristics were identified with a
      strong tendency to prevail subpopulations of molecules of lower hydrodynamic
      sizes with increasing LSCC stage. These findings demonstrated that the cleavage
      of aggregable aggrecan occurred in concrete peptide bonds within the CS-1 and CS
      2 attachment domains. These significant alterations were closely associated with
      the process of cartilage destruction, indicating the crucial role of aggrecan
      during LSCC.

PMID- 16574329
TI  - Developmental expression of two forms of arginase in Neurospora crassa.
AB  - N. crassa has two forms of arginase. The physiological role of multiple arginases
      is not understood. The two forms were shown to be differentially expressed from a
      single locus (aga) and both proteins are localized to the cytoplasm. The 36-kDa
      protein was expressed in minimal and arginine supplemented medium, whereas the 41
      kDa form was detected only in the presence of arginine. In this study we examined
      developmental expression of the two arginase transcripts and proteins in conidia
      and during conidial germination. Two novel observations are revealed, storage of
      both arginase proteins in conidia and temporal expression of aga transcripts
      during early germination. To better understand the role of arginase in conidia
      and the nature of the temporal expression, we examined the effects of related
      metabolites, arginine, ornithine, proline, glutamate and glutamine on protein
      storage and temporal expression. These metabolites were used as supplements or
      sole nitrogen sources. Storage of arginase protein was detected in all conidial
      samples examined except when glutamate was used as the nitrogen source. The aga
      temporal RNA expression early in germination was abolished when arginine related
      metabolites were used as nitrogen sources. The exception to this result is
      observed with glutamate where temporal expression was seen when glutamate was the
      sole nitrogen source and abolished with glutamate supplementation. The temporal
      expression result supports a unique role for arginase in glutamate accumulation
      early in germination whereas the protein storage result supports the existence of
      a novel pathway utilizing arginase for glutamate synthesis in asexual spore
      development.

PMID- 16574330
TI  - Predicting craving among cocaine users.
AB  - INTRODUCTION: Craving for cocaine seems to play an important role in the
      continued use of and dependence on the substance. AIMS: to describe
      characteristics of the craving phenomenon in a sample of cocaine users and to
      identify those that could predict the appearance of the phenomenon. METHOD: 205
      cocaine users attending an outpatient clinic were interviewed to assess patterns
      of drug consumption and characteristics of craving for the drug. FINDINGS:
      Subjects were mostly young (24.8+/-12.8 years) and male (86.2%). One hundred and
      two subjects (49.8%) were addicted to cocaine and the remainders (50.2%) were non
      addicted occasional cocaine users. The majority of subjects (60.5%) reported
      having had craving episodes during the previous week. Frequency of cocaine use
      during the previous month correlated with the number of reported craving fits
      (r=0.425; p<0.001) and with the duration of the craving fits (r=0.351; p<0.001).
      Users of crack reported more craving episodes than did the users of snorted
      cocaine (p<0.001) and the frequency of craving fits was inversely proportional to
      the duration of abstinence from the drug (r=-0.405; p<0.001). CONCLUSION: Both
      the method of drug consumption and the abstinence period elapsed since previous
      drug intake were identified as predictive parameters of craving.

PMID- 16574331
TI  - Validation of a brief screen for Post-Traumatic Stress Disorder with substance
      use disorder patients.
AB  - To evaluate a 4-item screen for Post-Traumatic Stress Disorder (PTSD) for use
      with patients diagnosed with substance use disorders, 97 patients were recruited
      from substance use disorder treatment clinics at a large medical center.
      Participants completed the self-administered 4-item PTSD screen. Psychologists
      interviewed patients using the Clinician Administered PTSD Scale (CAPS).
      Sensitivity and specificity were calculated using the CAPS as the criterion for
      PTSD. Results were compared to chart diagnoses. The prevalence of PTSD was 33%.
      The screen identified 91% of PTSD cases, where only 25% of PTSD cases were
      diagnosed in the medical chart. The screen demonstrated good test-retest
      reliability (r=.80) and yielded a sensitivity of .91 and specificity of .80 using
      a cut score of 3. Likelihood ratios indicate that the screen has good ability to
      detect PTSD in this population, and that patients with positive screens that do
      not meet criteria for PTSD are likely to report significant subthreshold
      symptoms. Screening for PTSD in SUD treatment settings is time efficient and may
      increase the detection of previously unrecognized PTSD.

PMID- 16574332
TI  - Distinct neuropsychological processes may mediate decision-making under
      uncertainty with known and unknown probability in gain and loss frames.
AB  - Decision-making under uncertainty has been studied in psychiatry, economic
      psychology, and neuroeconomics. Psychiatric patients (e.g., drug addicts) often
      show low degrees of aversion to potential danger. Investigation into
      neuropsychological processing underlying decision under uncertainty is important
      for medical treatments of neuropsychiatric disorders. In economic decision
      theory, choices under uncertainty with and without known probabilities of
      outcomes have been discriminated. Regarding decision-making under uncertainty
      with known probabilities (risk), Kahnemann-Tversky's prospect theory revealed
      that people tend to avoid uncertainty in potential gains (i.e., risk-aversion in
      a gain-frame); on the contrary, prefer uncertainty in potential losses (i.e.,
      risk-seeking in a loss-frame). Regarding choices between possible gains with
      known and unknown probabilities, Ellsberg demonstrated that, in a gain-frame,
      people tend to avoid uncertainty with unknown probabilities, more dramatically
      than uncertainty with known probabilities. This can be explained by
      risk/uncertainty aversion in the gain-frame, suggesting that uncertainty with
      known and unknown probabilities (i.e., risk and Knightian uncertainty,
      respectively) may possibly be processed by similar neuropsychological processing
      in the gain-frame. However, in spite of accumulating evidence in neuroimaging and
      neuroeconomic studies, it is still unknown whether probability and Knightian
      uncertainty in the loss-frame are mediated by similar neuropsychological
      processes as well. We propose that distinct neuropsychological processes may
      mediate potential losses with known and unknown probabilities, based on recent
      findings in neuroeconomics and our experiment. Importance of examining subjects'
      degree of Knightian uncertainty aversion for the prediction/treatment of drug
      addicts' risky behavior (e.g., needle-sharing) is also discussed.

PMID- 16574333
TI  - Weibel-Palade bodies exocytosis from endothelial cells: a possible mechanism
      mediating estrogen-related thromboembolism.

PMID- 16574334
TI  - The paradox of the modern mass media: probably the major source of social
      cohesion in liberal democracies, even though its content is often socially
      divisive.
AB  - The modern mass media (MM) is often regarded a mixture between a trivial waste of
      time and resources, and a dangerously subversive system tending to promote social
      division and community breakdown. But these negative evaluations are difficult to
      square with the fact that those countries with the largest mass media include the
      most modernized and powerful nations. It seems more plausible that the MM is
      serving some useful - perhaps vital - function. I suggest that modern mass media
      function as the main source of social cohesion in liberal democracies. The
      paradox is that this cohesive function is sustained in a context of frequently
      divisive media content. This media function evolved because modern MM produce an
      excess of media communications in a context of consumer choice which generates
      competition for public attention both within- and between-media. Competition has
      led the media to become increasingly specialized at gaining and retaining public
      attention. Social cohesion is the consequence of the mass media continually
      drawing public attention to itself, and to the extremely large, internally
      complex and interconnected nature of the MM system. The means by which attention
      is attracted are almost arbitrary, encompassing both novelty and familiarity and
      evoking a wide range of emotions both positive and negative. Driven to seek
      competitive advantage, modern mass media produce a wide range of material to
      cater to a vast range of interests; thereby engaging a great variety of
      individuals and social groupings. The consequence is that media content is
      typically self-contradictory and includes content which is offensive and
      potentially divisive; since what grabs the interest of some may offend or repel
      others. For instance, young men must be socially engaged, since they are
      potentially the most violent social group, yet the interests of young men include
      material that the majority of the population would find excessively aggressive,
      disrespectful, subversive or sexual. If the mass media is effectively to perform
      its crucial function of enabling social cohesion among a diverse and
      differentiated population, then modern liberal democracies need a broad margin of
      toleration and a widespread psychological capacity to endure dissent and
      disagreement.

PMID- 16574335
TI  - Queuing theory under competitive social foraging may explain a mathematical
      equivalence of delay and probability in impulsive decision-making.
AB  - Intertemporal and probabilistic decision-making has been studied in psychiatry,
      ecology, and neuroeconomics. Because drug addicts and psycopaths often make risky
      decisions (e.g., drug misuse and aggression), investigation into types of
      impulsivity in intertemporal and probabilistic choices (delay and probability
      discounting) are important for psychiatric treatments. Studies in behavioral
      ecology proposed that delay and probability discounting are mediated by the same
      psychological process, because a decrease in probability of winning corresponds
      to an increase in delay until winning. According to this view, odds-against
      winning (=1/p-1) in probabilistic choice corresponds to delay in intertemporal
      choice. This hypothesis predicts that preference of gambling (low degree of
      probability discounting) may be associated with patience, rather than impulsivity
      or impatience, in intertemporal choice (low degree of delay discounting).
      However, recent empirical evidence in psychiatric research employing pathological
      gamblers indicates that pathological gamblers are impulsive in intertemporal
      choice (high degrees of delay discounting). However, a hyperbolic discounting
      function (usually adopted to explain intertemporal choice) with odds-against
      (instead of delay) explain experimental data in probabilistic choice dramatically
      well. Therefore, an alternative explanation is required for the hypothetical
      equivalence of odds-against to delay. We propose that queuing theory (often
      adopted for analyzing computer network traffic) under a competitive social
      foraging condition may explain the equivalence. Our hypothesis may help
      understand impulsivity of psychiatrics in social behavior (e.g., aggression and
      antisocial behavior) in addition to non-social impulsivity in reward-seeking
      (e.g., substance misuse).

PMID- 16574336
TI  - Cancer chemoprevention: selenium as a prooxidant, not an antioxidant.
AB  - Although the average daily dietary selenium (Se) intake in the United States is
      consistently above the adult RDA of 55 microg Se/day, supranutritional
      supplements of 200 microg Se/day have been shown to provide chemopreventive
      benefits against several cancers, particularly prostate cancer. The hypothesis
      herein contends that selenium compounds with the greatest anticarcinogenic
      potency are likely to be sodium selenite with Se in the +4 oxidation state and
      methylseleninic acid. These compounds exert their cancer chemopreventive effects
      by directly oxidizing critical thiol-containing cellular substrates, and are more
      effective than the more frequently preferred (used) supplements of
      selenomethionine and Se-methylselenocysteine that lack oxidation capability.
      Selenate (+6 Se) the immediate precursor of selenite (+4 Se) can be metabolically
      reduced, and although less potent than the +4 Se compounds cited above, appears
      to be a more effective anticarcinogen than organic forms of dietary selenium.
      Apoptosis, an important, Se-induced anticarcinogenic mechanism, is accomplished
      by the direct oxidation of vicinal sulfhydryl groups in cysteine clusters within
      the catalytic domains of cellular enzymes (e.g., protein kinase C), and by the
      production of CH3Se-, which reacts with O2 to generate superoxide and other
      reactive oxygen species (ROS). Activated oncogenes "prime" cells for Se-induced
      prooxidative apoptosis thereby providing the needed margin for "killing" cancer
      cells while leaving normal, healthy cells unharmed. Selenoethers, such as
      selenomethionine and Se-methylselenocysteine are not oxidizing agents, and first,
      must be converted to methylselenol (CH3Se-) that can be directly oxidized to
      methylseleninic acid. The addition of methioninase, to selenomethionine, or beta
      lyase to Se-methylselenocysteine, rapidly produces significant amounts of
      methylselenol, which may be oxidized to methylseleninic acid or may react with O2
      to produce superoxide and ROS, resulting in anticarcinogenic activities
      comparable to selenite or methylseleninic acid. The relatively large amounts of
      selenomethionine or Se-methylselenocysteine needed to produce apoptosis in cancer
      cells compared with selenite or methylseleninic acid are a probable consequence
      of low tissue levels of the required enzymes. Even though many studies have
      consistently shown that selenomethionine is an ineffective anticarcinogen at
      doses corresponding to those currently allowed by the FDA, it has been chosen as
      the Se intervention agent in the 32,500-man (phase III), NCI-funded SELECT trial,
      which tests the effectiveness of dietary supplements of dietary supplements of Se
      and tocopherol, individually or in combination, in the prevention of prostate
      cancer. In 2013, when the data are in, the value of using Se supplements for
      cancer chemoprevention is likely to be underestimated.

PMID- 16574337
TI  - Spend less, live longer. The "thrifty aged" hypothesis.
AB  - Evolutionary biology has rejected any argument in favour of planned ageing. In
      this article, the metabolic changes that follow in ageing have been analysed, and
      in accordance with that, an evolutionary explanation for the senescence program
      has been proposed. Ageing is characterised by a set of metabolic features all of
      them designed to reduce energy expenditure and to promote energy storage.
      Otherwise, the undoubted beneficial effect to fitness that means to live longer
      could generate a conflict between parents and offspring for energy resources. The
      solution to that conflict is an adult economical individual, a "thrifty aged".
      The way to obtain this cheaper individual is through the genetically induced
      physiological changes that finally lead the process. In conclusion, it is
      proposed that ageing is the condition, imposed by natural selection, that let
      organisms to outlast the obligatory reproductive time.

PMID- 16574338
TI  - Application of quantum dots in quantitative proteomics for multiplex colour
      system assay.

PMID- 16574339
TI  - Heart failure as a consequence of ischemic mitral regurgitation (IMR): the hidden
      threat of the metabolic syndrome.

PMID- 16574340
TI  - You are what you ate: the Biosetpoint hypothesis.
AB  - The current epidemic of obesity has developed at a rate that cannot be attributed
      to genetic drift. Attempts to treat obesity using diet and activity have been
      largely disappointing. Genes are fixed at conception, but genetic expression is
      known to be influenced by nutriture during the stages of growth and development,
      these occurring in humans from conception through arrival at adulthood. Based on
      an extrapolation from existing data and cultural models, it is hypothesized that
      there is a mechanism by which diet and lifestyle habits present during the
      individual stages of growth and development help to define and program genetic
      expression in a way that resists change. It is through this mechanism that
      current nutritional and lifestyle practices have impacted genetic expression and
      contributed to the rapid development of resistant obesity. The details of the
      interaction between nutrition, lifestyle and genetic expression during growth
      must be examined, and intervention strategies devised for early stages of growth
      to prevent the seeds of obesity from taking root.

PMID- 16574341
TI  - Possible interactions of genetic and immuno-neuro-endocrine regulatory mechanisms
      in pathogenesis of congenital anomalies.
AB  - The process of organogenesis depends on genetic and environmental factors.
      Besides genetic background, congenital anomalies can also be influenced by micro
      environmental changes, which are related to maternal-foetal interactions followed
      by the production of cytokines, hormones, neurotransmitters, growth factors and
      biochemical mediators, and stress proteins. Pre-natal maternal stress, including
      infections, psychological stress and other teratogens, can influence a
      disregulation of maternal immune, endocrine and nervous systems, during
      pregnancy. This is a crucial condition for the abnormal growth and development of
      the foetus. Activated maternal immune system can alter the cytokine network and
      make it inadequate for normal embryogenesis and organogenesis. Heat-shock
      proteins play an important role in stress physiology repairing DNA errors or
      activating pro-inflammatory response. Regarded from this aspect, the altered
      cytokine network suggests aetiopathogenetic basis of congenital anomalies in
      neonates. It is our wish to point out our potentially harmful conditions in the
      development of congenital anomalies, as well as their control by using pre-natal
      and pre-conceptional diagnostics and treatment.

PMID- 16574342
TI  - Intestinal gases and flatulence: possible causes of occurrence.
AB  - All gases entrapped in closed body cavities are destined to be partially or
      completely absorbed. Intestinal gases often accumulate and cause flatulence. This
      paper proposes a simple concept of intestinal gas occurrence based on our
      knowledge on gas resorption in other body cavities. Compliance of intestinal and
      abdominal walls makes pressure in the liquid chyme bubbles near 760 mmHg.
      Intestinal gases are from three sources. Air can be swallowed, CO2 come from the
      gastric acid neutralisation and from intestinal bacterial colonies that also
      produce hydrogen and methane. In continuously mixed liquid chyme, the total
      pressure of blood gases is similar or lower than in the venous blood (<or=706),
      well below the bubble forming pressure (>or=760 mmHg). Some local production of
      bacterial gases with partial pressure of more than 90 mmHg is required, so the
      resulting small bowel bubbles would contain less than 20% of bacterial gases. If
      peristaltic mixing of chyme is prevented by an obstacle, local pressures of
      bacterial gases build up, form bubbles that fuse and finally make X-ray visible
      aeroliquid levels. Bacterial gases make almost 3/4 of the flatulence. Formation
      of bubbles destined to become flatulence might depend on altered rheological
      condition of the large bowel content, with local abundant production of bacterial
      gases near bacterial colonies. Gases are unable to diffuse rapidly through the
      dense liquid content and local accumulation allows formation of bubbles mainly of
      bacterial gases. Their pressure can be higher 760 mmHg, since they are stretching
      the thick content. Poor diffusion of gases keeps them almost free of blood gases
      and their entrance makes them bigger. As the content moves along the colon, the
      content is becoming more solid and gases are becoming entrapped in large bubbles.
      Some blood and bacterial gases are absorbed and exhaled, but the remaining
      quantity has no other escape except flatulence. Flatulence rich in bacterial
      gases might be the price for the large bowel water reabsorption. It seems that
      beside the peroral use of antibiotics active in the colon, little can be done to
      reduce flatulence.

PMID- 16574343
TI  - Psychophysiological determinants and concomitants of deficient decision making in
      pathological gamblers.
AB  - Psychophysiological responses are considered to be a mediating factor in the
      development of pathological gambling (PG) and PG has been associated with
      differential arousal levels during gambling. Yet little is known about the
      specific psychophysiological responses to wins and losses in PG. This study
      investigated heart rate (HR) and skin conductance responses (SCRs) during the
      Iowa Gambling Task (IGT) in an adult PG group (n=46) and a normal control (NC)
      group (n=47). Anticipatory psychophysiological reactions to disadvantageous and
      advantageous choices during the IGT and psychophysiological responses to wins and
      losses were measured. The PG group performed worse than the NC group on the IGT
      and exhibited lower anticipatory SCRs and HR decreases when pondering choices of
      disadvantageous card decks during the IGT. The PG group showed a decrease in HR
      after losses and wins, whereas the NC group showed a decrease in HR after losses,
      but an increase in HR after wins. Reward and punishment sensitivity as measured
      by the self-report BIS/BAS scale influenced IGT performance and
      psychophysiological responses, but in general these effects were similar for the
      PG group and the NC group. Lower anticipatory psychophysiological responses to
      disadvantageous choices in PG suggest impaired risk assessment in this group.
      Absence of a HR increase after wins possibly implies that reward sensitivity is
      decreased in PG. Because levels of reward and punishment sensitivity were
      associated with differential anticipatory HR responses to advantageous and
      disadvantageous decks, it would be advisable to include this taxonomy in studies
      on psychophysiological responses to rewards and losses.

PMID- 16574344
TI  - Analysis of SD sequences in completed microbial genomes: non-SD-led genes are as
      common as SD-led genes.
AB  - Shine-Dalgarno (SD) sequence has been considered as one of the common features of
      5' end untranslated region (5'UTR) of prokaryotic transcripts. However, more
      leaderless bacteria and archaea mRNAs are being increasingly reported in recent
      years. To understand the distribution of SD-led genes and non-SD-led genes, we
      have analyzed 162 completed prokaryotic genomes leading to various new
      conclusions and validations of previous smaller scale studies. The fact that the
      number of the SD-led genes among those genomes varies from 11.6% to 90.8% implies
      that the populations of non-SD-led genes as well as leaderless genes are
      significant. We found that there is a strong SD conserved region in genomes with
      high proportion of SD-led genes. Following a t-test we showed that SD sequence
      content (SDSC) has no correlation with GC content. We observed that the closely
      related phylogenetic microbes mostly possess a similar SDSC value, and archaeal
      nonleading genes possess higher SDSC. This study shows that the 5'UTR of
      prokaryotic genes are highly diverse, particularly when genomes of distantly
      related organisms are compared, suggesting that more flexible mechanisms are used
      for translation initiation process in various prokaryotes.

PMID- 16574345
TI  - Global gene expression of a murein (Braun) lipoprotein mutant of Salmonella
      enterica serovar Typhimurium by microarray analysis.
AB  - Braun/murein lipoprotein (Lpp) is one of the major outer membrane components of
      gram-negative enteric bacteria involved in inflammatory responses and septic
      shock. In previous studies, we reported that two copies of the lipoprotein (lpp)
      gene (designated as lppA and lppB) existed on the chromosome of Salmonella
      enterica serovar Typhimurium. Deletion of both lppA and lppB genes rendered
      Salmonella defective in invasion, motility, induction of cytotoxicity, and
      production of inflammatory cytokines/chemokines. The lppAB double-knockout (DKO)
      mutant was attenuated in mice, and animals immunized with this mutant were
      protected against subsequent challenge with lethal doses of wild-type (wt) S.
      Typhimurium. To better understand how deletion of the lpp gene might affect
      Salmonella virulence, we performed global transcriptional profiling of the genes
      in the wt and the lppAB DKO mutant of S. Typhimurium using microarrays. Our data
      revealed alterations in the expression of flagellar genes, invasion-associated
      type III secretion system genes, and transcriptional virulence gene regulators in
      the lppAB DKO mutant compared to wt S. Typhimurium. These data correlated with
      the lppAB DKO mutant phenotype and provided possible mechanism(s) of Lpp
      associated attenuation in S. Typhimurium. Although these studies were performed
      in in vitro grown bacteria, our future research will be targeted at global
      transcriptional profiling of the genes in in vivo grown wt S. Typhimurium and its
      Lpp mutant.

PMID- 16574346
TI  - Characterization of different expression patterns of calsarcin-1 and calsarcin-2
      in porcine muscle.
AB  - Calsarcins comprise a novel family of muscle-specific calcineurin-interacting
      proteins and play an important role in modulating both the function and substrate
      specificity of calcineurin in muscle cells. In this study, we cloned and
      characterized calsarcins from pig muscle. The deduced amino acid sequences of
      porcine calsarcin-1 (CS-1), calsarcin-2 (CS-2), and calsarcin-3 (CS-3) share the
      same putative calcineurin and alpha-actinin binding regions. Radiation hybrid
      mapping data indicate that CS-1 and CS-2 map to q2.1-2.5 of pig chromosome 8
      (SSC8) and q2.4 of pig chromosome 14 (SSC14), respectively. The mRNA expressions
      of both CS-1 and CS-2 are regulated in skeletal muscle similarly during postnatal
      development but not during prenatal development, indicating differences in
      function, additionally demonstrated by minute differences in cellular
      localization within Pig Kidney Epithelial cells (PK15). We provide the first
      evidence that CS-1 is abundantly expressed in porcine heart and has an expression
      pattern similar to the human gene. This result suggests that the pig may be a
      suitable animal model to study the function of calsarcins in human heart disease.

PMID- 16574347
TI  - Runx2-mediated regulation of the zinc finger Osterix/Sp7 gene.
AB  - The zinc finger transcription factor Osterix (Osx) regulates bone formation and
      osteoblast differentiation in vitro and in vivo. We investigated the
      transcriptional mechanisms underlying the mouse Osx expression by isolating and
      characterizing its 5' upstream region. We performed 5' RACE on mRNA isolated from
      murine chondroprogenitor cells and determined a cap site of Osx approximately -99
      nucleotides upstream of the initiation codon. Sequence analysis of this TATA-less
      promoter shows several putative response elements for Sox9, VDRE, Runx and Sp1.
      Transfection of the Osx promoter driving the luciferase reporter gene into
      C3H10T1/2 and ATDC5 cells shows a strong basal promoter activity between 565 bp
      and 2 kb. Deletion mutant analyses show that the most proximal 852 kb of the Osx
      promoter contains the highest activating domains, while strong repressive domains
      were identified between 1.8 and 2 kb. Over-expression experiments indicate that
      Runx2 significantly transactivates the Osx promoter by at least 2 fold indicating
      that Osx is downstream of Runx2 in mesenchymal cells. This up-regulation was
      abrogated when the Runx2 responsive element on the Osx promoter was mutated.
      Finally, we show that Runx2 specifically binds to this DNA element in the Osx
      promoter. Thus our results show for the first time Osx transcriptional regulation
      through the bone and cartilage related transcription factor Runx2.

PMID- 16574348
TI  - Pathogenesis of a Texas feline immunodeficiency virus isolate: an emerging
      subtype of clade B.
AB  - We have recently provided evidence that Texas feline immunodeficiency virus (FIV
      TX) isolates are an emerging subtype sharing a common ancestry with clade B
      isolates. Specific, pathogen-free cats were infected, intravenously, with 500,
      2000 or 8000TCID(50) of the FIV-TX53 virus to study the acute stage of infection.
      Infection of cats resulted in lymphadenopathy at 10 days post-infection (p.i.).
      By 7 weeks p.i., gag specific antibody could be detected from sera of all
      infected cats. Virus could be detected by culturing PBMC and by nested capsid
      PCR. A reduction in the absolute numbers of lymphocytes and neutrophils was
      observed in infected cats although there was no trend identified between this
      reduction and the viral dose administered. By 11 weeks p.i., the CD4(+)/CD8(+) T
      cell ratios from all infected cats had dropped from approximately 2 to below 1.
      While decrease in the ratio was dependent on the viral dose, the T cell ratios of
      cats receiving the highest dose had significantly dropped below 1 by 4-7 weeks
      p.i. This decrease in the ratio was accompanied by a sharp and temporal decline
      in the absolute CD4(+) T cells and a slight increase in the absolute CD8(+) T
      cell numbers with a dramatic expansion of cells with CD8beta(low) chain
      expression.

PMID- 16574349
TI  - Heterogeneity of Campylobacter jejuni and Campylobacter coli strains from healthy
      sheep.
AB  - The objectives of this study were to identify, at species level, thermophilic
      campylobacters isolated from clinically healthy sheep by a multiplex polymerase
      chain reaction (mPCR). The heterogeneity among Campylobacter jejuni and C. coli
      isolates was also investigated using a restriction fragment length polymorphism
      (RFLP) analysis of the flagellin (flaA) gene. Samples of intestinal contents,
      gall bladders and faeces were collected from 610 healthy sheep. While gall
      bladder samples were plated directly onto Preston agar, an enrichment stage was
      applied for intestinal and faecal samples. Of the 610 samples, 302 (49.5%) were
      positive for Campylobacter spp. Using a mPCR assay for species identification,
      103 (34.1%) were positive with C. jejuni-specific primers, while 100 (33.1%) were
      positive with C. coli-specific primers. Additionally, 16 (11.9%) of the
      intestinal content samples were positive for both species by mPCR. All the
      isolates identified as C. jejuni and C. coli were successfully subtyped by flaA
      typing. Of 203 isolates tested, 48 different flaA types were found. Twenty-six
      flaA types were identified among C. jejuni isolates and the remaining 22 from C.
      coli isolates.

PMID- 16574350
TI  - Expression pattern of fatty acid transport protein-1 (FATP-1), FATP-4 and heart
      fatty acid binding protein (H-FABP) genes in human term placenta.
AB  - Placental tissue from five women undergoing elective caesarean did not present
      differences in fatty acids or mRNA expression of FATP-1, FATP-4 and H-FABP in
      different placental locations. mRNA expression of FATP-1 and FATP-4 was
      significantly higher than H-FABP. The expression of L-FABP was too low in
      placenta for accurate quantification.

PMID- 16574352
TI  - Torque rheological parameters to predict pellet quality in extrusion
      spheronization.
AB  - This study explored the feasibility of predicting the quality of microcrystalline
      cellulose (MCC) pellets prepared by extrusion-spheronization using torque
      rheological characterization. Rheological properties of eleven MCC grades as well
      as their binary mixtures with lactose (3:7) at various water contents were
      determined using a mixer torque rheometer (MTR). Derived torque parameters were:
      maximum torque and cumulative energy of mixing (CEM). CEM values of MCC powders
      (CEM((MCC))) could be attributed to their physical properties such as
      crystallinity, V(low P) and V(total) (volumes of mercury intruded in their pores
      at low pressure and the total intrusion volume), bulk and tapped densities. For
      both MCC powders and their binary mixtures, strong correlation was observed
      between their torque parameters and the properties of their pellets formed with
      30 and 35% (w/w) water. Since this relationship was valid over a broad water
      content range, rheological assessment for pre-formulation purposes need not be
      performed at optimized water contents. These results demonstrated the usefulness
      of torque rheometry as an effective means of comparing and evaluating MCC grades
      especially when substitution of equivalent grades is encountered. In so doing,
      the tedious and expensive pre-production (pre-formulation and optimization) work
      can be considerably reduced.

PMID- 16574351
TI  - Low dose estrogens inhibit coronary artery atherosclerosis in postmenopausal
      monkeys.
AB  - OBJECTIVES: To determine if low dose conjugated equine estrogens (CEE) result in
      a reduction of coronary artery atherosclerosis progression, and to relate these
      findings to previous studies using the traditional dose. METHODS: Adult female
      monkeys (Macaca fascicularis) were fed an atherogenic diet for 10 months, to
      induce fatty streaks and small plaques comparable to those present in early
      postmenopausal women, and then ovariectomized and treated orally with: CEE (0.30
      mg/day women's equivalent dose, n=28) or placebo (n=25) daily for 24 months. Body
      weight and estradiol were measured at 3, 6, 12 and 18 months and plasma lipids
      were measured at baseline and every 6 months. RESULTS: Despite the lack of effect
      on plasma lipid profiles, monkeys treated with low dose CEE had marked reductions
      in coronary artery atherosclerosis plaque extent (intimal area) in all three main
      coronary arteries: left anterior descending artery (52% less, 0.044 mm(2) versus
      0.091 mm(2), p=0.04); left circumflex artery (62% less, 0.045 mm(2) versus 0.119
      mm(2), p=0.006) and right circumflex artery (42% less, 0.018 mm(2) versus 0.031
      mm(2), p=0.20). The overall mean coronary atherosclerosis extent was 52% lower in
      CEE treated animals (0.042 mm(2) versus 0.088 mm(2), p=0.02). CONCLUSION: Low
      dose CEE (0.30 mg/woman/day equivalent) was effective in reducing coronary
      atherosclerosis and the magnitude of the protection was comparable to previously
      reported studies using doses equivalent to 0.625 mg/woman/day. This study
      provides an experimental basis for the assumption that low dose CEE may be as
      effective as the traditional dose in inhibiting coronary atherosclerosis
      progression in early postmenopausal subjects.

PMID- 16574353
TI  - Modelling intestinal absorption of salbutamol sulphate in rats.
AB  - The objective was to develop a semiphysiological population pharmacokinetic model
      that describes the complex salbutamol sulphate absorption in rat small intestine.
      In situ techniques were used to characterize the salbutamol sulphate absorption
      at different concentrations (range: 0.15-18 mM). Salbutamol sulphate at
      concentration of 0.29 mM was administered in presence of verapamil (10 and 20
      mM), grapefruit juice and sodium azide (NaN3) (0.3, 3 and 6 mM). Different
      pharmacokinetic models were fitted to the dataset using NONMEM. Parametric and
      non-parametric bootstrap analyses were employed as internal model evaluation
      techniques. The validated model suggested instantaneous equilibrium between
      salbutamol sulphate concentrations in lumen and enterocyte, and the salbutamol
      sulphate absorption was best described by a simultaneous passive diffusion (ka =
      0.636 h(-1)) and active absorption (VMax = 0.726 mM/h, Km = 0.540 mM) processes
      from intestinal lumen to enterocyte, together with an active capacity-limited P
      gp efflux (V'max = 0.678 mM/h, K'm = 0.357 mM) from enterocyte to intestinal
      lumen. The extent of salbutamol sulphate absorption in rat small intestine can be
      improved by NaN3, grapefruit juice and verapamil.

PMID- 16574354
TI  - Structural investigations on nanoemulsions, solid lipid nanoparticles and
      nanostructured lipid carriers by cryo-field emission scanning electron microscopy
      and Raman spectroscopy.
AB  - Recently, colloidal dispersions based on solid lipids (solid lipid nanoparticles,
      SLN) and mixtures of solid and liquid lipids (nanostructured lipid carriers, NLC)
      were described as innovative carrier systems. A spherical particle shape is the
      basis of features such as a high loading capacity and controlled drug release
      characteristics due to smaller lipid-water interfaces and longer diffusion
      pathways when compared to thin platelets. The structures of SLN and the influence
      of oil load (NLC) on particle properties were investigated by photon correlation
      spectroscopy (PCS), laser diffractometry (LD), cryo-field emission scanning
      electron microscopy (cryo-FESEM), Raman spectroscopy and infrared spectroscopy
      (IR), and compared to a conventional nanoemulsion. PCS and LD data show similar
      size and size distribution for SLN and NLC (approximately 210 nm, polydispersity
      index approximately 0.15) and suggested a long term physical stability for the
      dispersions which had been stored for up to 12 months at different temperatures.
      Using cryo-FESEM droplets (for the nanoemulsion) and almost spherical particles
      for SLN and NLC were observed. Raman spectroscopy resulted in spectra for NLC
      that are weighted to the SLN spectra, suggesting an undisturbed crystal
      structure. Infrared spectra of the NLC are predominantly SLN in nature.
      Importantly the SLN bands are unshifted in the NLC spectrum indicating that the
      crystalline structure is unaffected by the presence of the oil.

PMID- 16574355
TI  - Characterization of diffusion of macromolecules in konjac glucomannan solutions
      and gels by fluorescence recovery after photobleaching technique.
AB  - Konjac glucomannan (KGM) is a neutral polysaccharide with interesting properties
      as gelling agent and thickener. Its peculiar biodegradability, being not
      degradable in the small intestine but degradable by the anaerobic human
      intestinal bacteria, turn it into a promising candidate for colonic drug delivery
      systems. In this study aqueous systems (0.5%, w/v,) of KGM from three different
      origins and their mixtures with xanthan gum (XG) (1:1) were evaluated as regards
      their rheological properties and the diffusion coefficients and mobile fraction
      of macromolecules (dextrans of different molecular weight). Rheological data
      illustrate the synergism between KGM and XG at a stoichiometric relationship 1:1.
      Moreover, fluorescence recovery after photobleaching (FRAP) data indicate that
      diffusion of probes through the polysaccharide systems cannot be completely
      explained by the macroscopic properties of the medium but it is related to their
      molecular size and as a consequence to a sieving mechanism. The strong
      differences between KGM from different suppliers suggest the convenience of
      establishing specifications for this material in order to use it as
      pharmaceutical excipient.

PMID- 16574356
TI  - Chemotherapy with hybrid liposomes for lymphoma without drugs in vivo.
AB  - Hybrid liposomes composed of dimyristoylphosphatidylcholine (DMPC) and
      polyoxyethylene (n) dodecyl ether (C(12)(EO)(n), n=21 and 25) were prepared with
      the method of sonication. Clear solution of hybrid liposomes having hydrodynamic
      diameter of 80-100 nm could be maintained over 3 weeks. Hybrid liposomes induced
      apoptosis for human lymphoma (MOLT-4 and RAJI) cells in vitro. No toxicity was
      observed in the rats after intravenously injecting hybrid liposomes in vivo. We
      clearly demonstrated that a mouse model of lymphoma was established and prolonged
      survival was obtained in mice models of lymphoma after the treatment with hybrid
      liposomes without drugs in vivo. The results in this study should support the
      prolonged survival for patients with lymphoma in clinical applications.

PMID- 16574357
TI  - Physicochemical characteristics and bioavailability of a novel intestinal
      metabolite of ginseng saponin (IH901) complexed with beta-cyclodextrin.
AB  - In an effort to improve the bioavailability (BA) of the insoluble compound 20-O
      (beta-d-glucopyranosyl)-20(S)-protopanaxadiol (IH901), we prepared beta
      cyclodextrin (betaCD) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) inclusion
      complexes containing IH901. IH901 is a major metabolite formed by intestinal
      bacteria from protopanaxadiol ginseng saponins. We developed and validated an
      HPLC-based method to measure IH901 levels from samples prepared in vitro. The
      phase solubility profiles with both cyclodextrins (CDs) were classified as AL
      type, indicating the formation of a 1:1 stoichiometric inclusion complex.
      Stability constants (Ks) calculated from the phase solubility diagrams showed
      that the betaCD complex was more stable than the HPbetaCD complex. Consequently,
      complexes of IH901 and betaCD were prepared by a freeze-drying method and were
      analyzed by fourier transformation-infrared spectroscopy (FT-IR), X-ray
      diffraction, differential scanning calorimetry (DSC), and scanning electron
      microscopy (SEM). From these physicochemical characterizations, we confirmed the
      presence of a new solid phase in the freeze-dried samples. The IH901 released
      from the complex in a pH 1.2 solution, the pH range of gastric fluids, was
      considerably lower than the amount released in the other solutions. The IH901
      released from the complex in pH 6.8 solution, the range of intestinal fluids, was
      9.0-fold greater than pure IH901 powder. However, the amount of IH901 released
      from the complex in pH 4.0-8.0 was less than 20%. After oral administration of
      the IH901-betaCD inclusion complex (30 mg/kg IH901) into rats, plasma
      concentrations were determined by LC/MS/MS. The peak concentration (Cmax) for the
      inclusion complex was 2.8-fold higher than that for pure IH901 powder. The BA,
      calculated from the ratio of the AUCoral to the AUCi.v., for the pure IH901
      powder, the IH901-betaCD physical mixture, and the inclusion complex was 3.52,
      4.34, and 6.57%, respectively. These results indicate that the BA for the
      inclusion complex was 1.9-fold higher than that for the pure IH901 powder.

PMID- 16574358
TI  - Ferutinin stimulates nitric oxide synthase activity in median eminence of the
      rat.
AB  - Several species of Ferula genus have been used in folk medicine in digestive
      disorders, rheumatism, headache, arthritis, and as tranquilizers, antispasmodic
      and aphrodisiac. From the dry and powdered roots of Ferula hermonis Boiss was
      extracted the oxygenated sesquiterpene 1,5-trans-daucane type: ferutinine (1).
      The structure of (1) was established by spectroscopic methods as: IR, (1)H RMN,
      (13)C RMN, COSY, HMBC, HMQC, NOESY, EIMS, and CIMS. The possible signaling
      pathway of ferutinin (1) in nervous tissue in vitro was assessed and the results
      showed that this compound is able to increase nitric oxide synthase activity and
      inositol monophosphate accumulation (49%, each) in the median eminence of the rat
      brain, suggesting that compound (1) is associated to the activation of
      phosphoinositide breakdown and nitric oxide production (NO), the last is a
      gaseous intercellular messenger known to play a broad role in human biology from
      homeostasis to pathology.

PMID- 16574359
TI  - Pharmacological activities investigation of crude extracts and fractions from
      Qualea grandiflora Mart.
AB  - This study investigates pharmacological activities of crude hydroalcoholic
      extract and fractions of Qualea grandiflora Mart. leaves employing different
      experimental models using mice. The treatment with crude hydroalcoholic extract
      (EH) in a dose of 500 mg/kg, i.p. caused: signs of central nervous system
      depressant action in the Hippocratic screening test, confirmed by the
      potentiation of sodium pentobarbital sleeping time. Increasing in the latency
      time of hot plate assay that indicate an analgesic effect; significantly delaying
      of the onset of clonic PTZ convulsions, increasing in the time for death,
      suppressing of the tonic PTZ convulsion, and decreasing of severity and number of
      convulsions. The median lethal dose of EH was 1.321 mg/kg. The convulsions
      induced by PTZ, ethyl ether fraction (300 mg/kg, i.p.) was more active in
      increasing the latency time for first convulsion, moreover, the hexane fraction,
      at the same dose, was more active in increasing the time for death and/or
      avoiding the death. Both did not cause disturbance in motor coordination at the
      dose of 500 mg/kg, assessed by rotarod test. These results suggest that the crude
      extract of leaves of Qualea grandiflora Mart. has a central nervous system
      depressant action, an analgesic effect and behave as a potential anticonvulsant.

PMID- 16574360
TI  - Antifungal activity of some coumarins obtained from species of Pterocaulon
      (Asteraceae).
AB  - Fractionation of antifungal hexane extracts of the aerial parts of three
      Pterocaulon spp., Pterocaulon alopecuroides, Pterocaulon balansae and Pterocaulon
      polystachyum (Asteraceae) from South Brazil traditionally used to treat animal
      mycoses, afforded the coumarins 5-methoxy-6,7-methylenedioxycoumarin, 7-(2',3'
      epoxy-3'-methylbutyloxy)-6-methoxycoumarin, 6,7-methylenedioxycoumarin (ayapin),
      along with a mixture of 6-hydroxy-7-(3'-methylbutyl-2'-en-oxy)-coumarin
      (prenyletin) and 6-methoxy-7-(3'-methylbutyl-2'-en-oxy)-coumarin (prenyletin
      methyl-ether). Among the different components of the active extracts, only the
      mixture of prenyletin and prenyletin-methyl-ether isolated from Pterocaulon
      polystachyum showed activity against Cryptococcus neoformans, Microsporum
      gypseum, Trichophyton rubrum and Trichophyton mentagrophytes. Nevertheless their
      MIC values were higher than the MIC of the original extracts, suggesting that the
      mixture but not only one compound would be the responsible for the activity
      detected in these Pterocaulon species.

PMID- 16574361
TI  - Collection of post mortem data: DVI protocols and quality assurance.
AB  - In many countries forensic odontologists are members of the Disaster Victim
      Identification (DVI) team. As part of their post mortem (PM) tasks work on the
      incident site may include securing and preserving the dental material and
      evidence before transport to the mortuary. In the autopsy room the main aim is to
      register the PM dental status. Photographs and radiographs are essential
      documentations in addition to a conventional registration of the dental status.
      Abbreviations in the registration may be used if agreed with the ante mortem (AM)
      team. Dental age estimation may be an aid in the sorting process and especially
      in victims without previous dental treatment. Interpol has a form set as part of
      their DVI manual. Forensic odontologists working in pairs and checking each other
      will act as quality assurance (QA) as suggested by International Organization for
      Forensic Odonto-Stomatology (IOFOS). Direct entry into the computer program as
      part of the registration in the autopsy room may save time and manpower.

PMID- 16574362
TI  - Neurological complications in beta-thalassemia.
AB  - Over the years, several reports have demonstrated involvement of the nervous
      system in beta-thalassemia patients. Neurological complications have been
      attributed to various factors such as chronic hypoxia, bone marrow expansion,
      iron overload, and desferrioxamine neurotoxicity. In most cases, neurological
      involvement does not initially present with relevant signs or symptoms (i.e., is
      subclinical) and can only be detected during neurophysiological or neuroimaging
      evaluation. Abnormal findings in the visual, auditory, and somatosensory evoked
      potential recordings are mainly attributed to DFO neurotoxicity. On the other
      hand, nerve conduction velocity abnormalities are associated either to chronic
      hypoxia and older age or to hemosiderosis, whether by means of pancreas
      involvement or not. Neuropsychological studies available reveal a considerably
      high prevalence of abnormal IQ, not correlating, however, to factors such as
      hypoxia or iron overload. It is proposed that factors associated to severe
      chronic illness, rather than the disease per se, could be responsible for these
      findings. Such factors include regular school absence due to transfusions and
      frequent hospitalizations, physical and social restrictions resulting from the
      disease and its treatment, abnormal mental state due to the awareness of being
      chronically ill, and, last, the overly protective family attitude that leads to
      restricted initiative and psychosocial development. As life expectancy for beta
      thalassemia patients extends, the use of neurophysiologic and neuropsychologic
      monitoring becomes imperative, enabling early detection of neural pathway
      impairment and allowing for appropriate management, in order to achieve a better
      life quality for this patient group.

PMID- 16574363
TI  - Voltammetric sensor for tinidazole based on poly(carmine) film-modified electrode
      and its application.
AB  - A poly(carmine) film-modified glassy carbon electrode (GCE) was fabricated and
      the electrochemical behavior of tinidazole at the modified electrode was
      investigated by electrochemical methods. A well-defined reduction peak was
      observed at 0.61 V and was applied for the determination of tinidazole. Compared
      with that at a bare GCE, the reduction peak potential of tinidazole shifted
      negatively and the reduction peak current increased significantly. The influences
      of some parameters on the reduction of tinidazole were also examined. Based on
      the experimental data, a possible mechanism was proposed for the electrochemical
      reaction of tinidazole at the modified electrode. It was found that the reduction
      peak current was proportional to the concentration of tinidazole in the range
      from 1.0 x 10(-7) to 5.0 x 10(-5)mol L(-1). The detection limit was about 1.0 x
      10(-8)mol L(-1) after accumulation 90 s at a constant potential of 0.0 V. The
      proposed method was applied to determine tinidazole in drugs and the result was
      satisfied.

PMID- 16574364
TI  - Identification of phenolic compounds in rosemary honey using solid-phase
      extraction by capillary electrophoresis-electrospray ionization-mass
      spectrometry.
AB  - Complex extracts of rosemary honey constituents often require very effective
      separation techniques to allow the identification of different compounds.
      Capillary electrophoresis (CE) coupled to mass spectrometry (MS) detection can
      provide structure-selective information about the analytes in such matrices and
      has turned out to be an attractive alternative to HPLC methods. A simple and cost
      effective analytical method involving solid-phase extraction (SPE) and capillary
      zone electrophoresis coupled to electrospray ionization-ion trap mass
      spectrometry (CZE-ESI-MS) to identify and characterize phenolic compounds in
      rosemary honey is described. The SPE, CE and ESI-MS parameters were optimized in
      order to maximize the number of phenolic compounds detected and the sensitivity
      of their determination. All CE-ESI-MS experiments were performed with uncoated
      fused-silica capillaries and an alkaline volatile buffer system consisting of 100
      mM NH(4)Oac with 10% of 2-propanol at pH 10. Since sheath liquids can made
      significant effects on the sensitivity in typical CE-ESI-MS application, the
      effect of type and flow rate of the sheath liquid on the sensitivity of phenolic
      compounds were investigated. As result, the best sensitivity was obtained with a
      sheath liquid containing 2-propanol/water 60:40 (v/v) and 0.1% (v/v) of
      triethylamine at 3 microL/min in the negative ion mode. We describe the first
      method for the analysis of phenolic compounds in rosemary honey at mg/L levels by
      using a simple SPE before CE-ESI-MS analysis.

PMID- 16574365
TI  - Simultaneous determination of Gastrodin and Ligustrazine hydrochloride in dog
      plasma by gradient high-performance liquid chromatography.
AB  - A novel reversed-phase HPLC method was developed for the simultaneous
      determination of Gastrodin (Gas) and Ligustrazine hydrochloride (LZH) in dog
      plasma after oral administration of the preparation 'Tianxiong Capsule'. The
      assay involves deproteinization, extraction and subsequent detection with a
      gradient solvent system at two different wavelengths. Retention times were 10.6
      and 18.9 min for Gas and LZH, respectively. Linear responses were observed over a
      wide range (0.40-200.0 microg/ml for Gas and 0.0999-39.96 microg/ml for LZH) in
      plasma. The mean intra- and inter-assay variation coefficients were 2.7 and 3.4%
      for Gas and 3.4 and 4.2% for LZH, respectively. The average extract recoveries
      were 76.77% for Gas and 75.8% for LZH. This assay has been successfully used to
      provide pharmacokinetic data for Gastrodin with oral administration of Tianxiong
      capsules.

PMID- 16574366
TI  - Chemical investigation on Sijunzi decoction and its two major herbs Panax ginseng
      and Glycyrrhiza uralensis by LC/MS/MS.
AB  - Sijunzi decoction consists of Panax ginseng, Poria cocos, Atractylodes
      macrocephala and Glycyrrhiza uralensis. High performance liquid chromatography
      coupled with tandem mass spectrometry (LC/MS(n)) was applied to identify and
      characterize three types of active components, ginsenoside (from P. ginseng),
      flavonoid and triterpenoid (from G. uralensis) in Sijunzi decoction. Spectra of
      MS and MS/MS from [M+Na](+) ions of ginsenosides were acquired and interpreted
      for their identification. Fragmentations with losing masses of 194 or 176Da were
      the characteristic ions of triterpenoids in the MS/MS analysis. A characteristic
      fragment ion of the aglycon moiety at m/z 257 from source collision-induced
      dissociation was observed for flavonoid. LC/MS was also applied for the
      comparison of relative peak area of major active components between Sijunzi
      decoction and the single herb extracts. The concentration ratios of major active
      components detected in the individual herbs of P. ginseng and G. uralensis were
      found different from those in Sijunzi decoction. The experimental data indicated
      that the decocting process could result in the difference in the amount of active
      components.

PMID- 16574367
TI  - Analysis of neolignans compounds of Piper regnellii (Miq.) C. DC. var. pallescens
      (C. DC.) Yunck by HPLC.
AB  - A high performance liquid chromatographic (HPLC) method was developed and
      validated for quantitative determination of neolignans in extracts of Piper
      regnellii var. pallescens. The analysis were carried out on a Metasil ODS column
      (150 mm x 4.6 mm, 5 microm) at 30 degrees C, using as mobile phase acetonitrile
      water (60:40, v/v) containing 2% acetic acid. The flow rate was 1.0 ml/min and
      the detection was at 280 nm. The validation using conocarpan as standard
      demonstrated that the method presents linearity (linear correlation
      coefficient=0.9991), precision (relative standard deviation <5%) and accuracy
      (mean recovery=104.55%) in the concentration range 31.25-500 microg/ml. The limit
      of detection (LOD) was 1.68 microg/ml and the limit of quantitation was 5.60
      microg/ml. This method allowed the identification and quantification of
      conocarpan, eupomatenoid-5 and eupomatenoid-6 in the hydroethanolic extracts
      obtained from the leaves, stems and roots by maceration process. All the extracts
      showed the same chromatographic profile, being that the extract of the roots
      presented the highest concentration of neolignans.

PMID- 16574368
TI  - Differential scanning calorimetry as a screening technique in compatibility
      studies of DHEA extended release formulations.
AB  - Differential scanning calorimetry (DSC) was used as a screening technique for
      assessing the compatibility of DHEA as ternary complex with alpha-cyclodextrin
      and glycine (c-DHEA) with some excipients suitable for preparation of sustained
      release matrix tablets by direct compression. The effect of sample mechanical
      treatment due to the compression process was also evaluated. In order to
      investigate the possible interactions between the components, the DSC curves of c
      DHEA and each selected excipient were compared with those of their 1:1 w/w
      physical mixtures, before and after compression, in order to evaluate any
      possible solid state modification. FT-IR spectroscopy and X-ray powder
      diffractometry were used as complementary techniques to adequately implement and
      assist in interpretation of the DSC results. On the basis of DSC results, c-DHEA
      was found to be compatible with xanthan gum, hydroxypropylmethylcellulose, sodium
      starch glycolate (Explotab), polyvinylacetate-polyvinylpirrolidone (Kollidon SR)
      and sodium chloride. Some drug-excipient interaction was observed with dextrate
      hydrate (Emdex), mannitol and Magnesium stearate. Finally, the behaviour of the
      complete formulation, in the presence of all the excipients selected by means of
      the compatibility study, was investigated, in order to verify the absence of
      reciprocal interactions among the components.

PMID- 16574369
TI  - Expression of the alpha7, alpha4 and alpha3 nicotinic receptor subtype in the
      brain and adrenal medulla of transgenic mice carrying genes coding for human AChE
      and beta-amyloid.
AB  - Human AChE-enzyme (hAChE) enhances the over-expression of beta-amyloid (Abeta)
      containing plaques in the brain of transgenic mice (APP(SWE)/hAChE-Tg) carrying
      mutated genes for human amyloid precursor protein (APP(SWE)) and hAChE. In this
      study, we showed that interaction of hAChE with Abeta affects the plasticity of
      the alpha7 nicotinic acetylcholine receptors (nAChRs) both in the brain and
      adrenal medulla. An age-related increase in the (125)I-alphabungarotoxin ((125)I
      alphaBTX) binding (specific to alpha7 nAChRs) was observed in the adrenal medulla
      of 3, 7 and 10 months old control mice. In contrast, a significant decrease in
      (125)I-alphaBTX binding was detected in the adrenal medulla of 10 months old
      APP(SWE)/hAChE-Tg. A significantly higher alpha7 nAChR mRNA level was observed in
      the brain of APP(SWE)/hAChE-Tg at 3 and 7 months of age and in the adrenal
      medulla at 3 and 10 months of age compared to those of the control mice. The
      alpha3 nAChR mRNA level was significantly higher in the brain of APP(SWE)/hAChE
      Tg at 3 months of age and in the adrenal medulla at 10 months of age. The alpha4
      nAChR mRNA level remained unchanged in the brain and adrenal medulla of
      APP(SWE)/hAChE-Tg for all age groups. Based on these observations, we conclude
      that a high load of Abeta and an over-expression of hAChE induce differences in
      the expression of the nAChR subtypes at various ages in the brain and in the
      adrenal medulla of hAChE/APP(SWE)Tg mice. The findings may have implications for
      a better understanding the underlying mechanism for AD-related pathogenesis.

PMID- 16574370
TI  - [Evaluation of the iliac crest as anatomic landmark for spinal anaesthesia in
      pregnant women].
AB  - OBJECTIVE: Estimate the relevance of the Tuffier line, which connects both iliac
      crests, in analyzing the location of the puncture point for spinal anaesthesia
      for pregnant women. STUDY DESIGN: Prospective. PATIENTS AND METHODS: The age,
      weight, height, body mass index (BMI) and uterine height, (HU) of 121 patients
      admitted in the delivery room in July 2005, were recorded. The intersection point
      of the Tuffier line with the rachis was recorded in seating and sleeping
      positions. The corresponding vertebral level was verified by counting spiny
      apophyses from C7. RESULTS: The Tuffier line crossed the spine at the expected
      level for 29.7% of the patients. The intersection point was below the expected in
      6.6% of the cases and above in 63.7% of the cases. Only the weight and the BMI
      were significantly connected with stronger probability of error (p=0.001).
      CONCLUSION: The error level with this method is important and comparable to error
      level in the series published in patients who are not pregnant woman. The main
      risk is the spinal injury, since the level of ending of the spinal cord is
      variable. It seems safe to use another method of location, especially with
      patients experiencing excessive weight.

PMID- 16574371
TI  - Anti-inflammatory effect of Poncirus trifoliata fruit through inhibition of NF
      kappaB activation in mast cells.
AB  - Mast cell-mediated allergic inflammation is involved in many diseases such as
      asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and
      production of pro-inflammatory cytokines including tumor necrosis factor (TNF)
      alpha and interleukin (IL)-6 with immune regulatory properties. We investigated
      the effect of the fruits of Poncirus trifoliata (L.) Raf (Rutaceae) (FPT) on
      expression of pro-inflammatory cytokines by activated human mast cell line, HMC
      1. FPT dose dependently decreased the gene expression and production of TNF-alpha
      and IL-6 on phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187
      stimulated HMC-1 cells. In addition, FPT attenuated PMA and A23187-induced
      activation of NF-kappaB indicated by inhibition of degradation of I kappa B
      alpha, nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB
      dependent gene reporter assay. Our in vitro studies provide evidence that FPT
      might contribute to the treatment of mast cell-derived allergic inflammatory
      diseases.

PMID- 16574372
TI  - Remarkable expansions of an X-linked reproductive homeobox gene cluster in rodent
      evolution.
AB  - Rhox is a recently identified cluster of 12 X-linked homeobox genes in mice. The
      expression pattern of Rhox genes during postnatal testis development corresponds
      to their chromosomal position, much like the colinear gene regulation of the Hox
      gene clusters during animal embryonic development. We here report the
      identification of 18 additional Rhox genes and 3 pseudogenes in mice. Comparative
      analyses of the mouse, rat, human, dog, cow, opossum, and chicken genomes suggest
      that the Rhox cluster originated in the common ancestor of primates and rodents.
      It subsequently underwent two remarkable expansions, first in the common ancestor
      of mice and rats and then in mice. Positive selection promoting amino acid
      substitutions was detected in some young Rhox genes, suggesting adaptive
      functional diversification. The recent expansions of the Rhox cluster provide an
      opportunity to study the mechanism and origin of colinear gene regulation, but
      they may also undermine the utility of mouse models for understanding the
      development and physiology of the human reproductive system.

PMID- 16574373
TI  - A wide-range phylogenetic analysis of Zic proteins: implications for correlations
      between protein structure conservation and body plan complexity.
AB  - We compared Zic homologues from a wide range of animals. Striking conservation
      was found in the zinc finger domains, in which an exon-intron boundary has been
      kept in all bilateralians but not cnidarians, suggesting that all of the
      bilateralian Zic genes are derived from a single gene in a bilateralian ancestor.
      There were additional conserved amino acid sequences, ZOC and ZF-NC. Combined
      analysis of the zinc finger, ZOC, and ZF-NC revealed the presence of two classes
      of Zic, based on the degree of protein structure conservation. The "conserved"
      class includes Zic proteins from the Arthropoda, Mollusca, Annelida,
      Echinodermata, and Chordata (vertebrates and cephalochordates), whereas the
      "diverged" class contains those from the Platyhelminthes, Cnidaria, Nematoda, and
      Chordata (urochordates). The result indicates that the ancestral bilateralian Zic
      protein had already acquired an entire set of conserved domains, but that this
      was lost and diverged in the platyhelminthes, nematodes, and urochordates.

PMID- 16574374
TI  - Stress decreases, while central nucleus amygdala lesions increase, IL-8 and MIP
      1alpha gene expression during tissue healing in non-human primates.
AB  - Stress impairs healing and in part this effect is thought to be mediated by
      glucocorticoids. However, the brain systems that underlie the effects of stress
      on healing remain to be determined. Since the central nucleus of the amygdala
      (CeA) plays a role in mediating an individual's behavioral and physiological
      reactivity to stress, we investigated, in rhesus monkeys, whether selective
      lesions of the CeA altered the gene expression of chemokines (IL-8 and MIP
      1alpha) that are associated with early dermal healing. We used rhesus monkeys
      because they provide an excellent animal model to investigate brain mechanisms
      relevant to human stress, anxiety, and psychopathology. Hypothalamic-pituitary
      adrenal (HPA) activity was assessed in the monkeys prior to the wound healing
      experiment demonstrating that the CeA lesions reduce HPA activity. In the healing
      experiment, stress decreased IL-8 and MIP-1alpha gene expression in both CeA
      lesioned and non-lesioned animals. Conversely, the CeA lesions increased the
      tissue expression of IL-8 and MIP-1alpha mRNA prior to and after stress exposure.
      These results demonstrate that in primates the CeA is a key brain region involved
      in the regulation of processes associated with wound healing. Because of brain
      and behavioral similarities between rhesus monkeys and humans, these results are
      particularly relevant to understanding brain mechanisms that influence healing in
      humans.

PMID- 16574375
TI  - Fostering adaptive responses and head control in students with multiple
      disabilities through a microswitch-based program: follow-up assessment and
      program revision.
AB  - A program was recently developed to promote adaptive responses and upright head
      position in students with multiple disabilities through the use of microswitch
      clusters (i.e., combinations of two microswitches). The five students exposed to
      the program showed a significant increase in adaptive responses performed with
      head upright. The first purpose of this study was to carry out a long-term follow
      up assessment of the five students' frequencies of adaptive responses and
      percentages of those responses combined with head upright. Recordings were also
      made of the length of time the head position was kept during each stimulation
      period following a successful response event and through the sessions. The second
      purpose of this study was to arrange a program revision for the students with
      less favorable data on head upright. The revision consisted of making the
      stimulation following successful response events synchronous with head upright
      with a maximum duration of 9s per event. The results of the follow-up assessment
      showed that two of the students kept the upright head position for nearly the
      entire stimulation periods that followed successful response events as well as
      much of the session time. The other three students kept such position for small
      or intermediate portions of the stimulation periods and of the session time. For
      these three students, the revised program was applied with substantial benefits.
      Implications of the findings were discussed.

PMID- 16574376
TI  - Teratogenic effects of ethanol exposure on zebrafish visual system development.
AB  - Ethanol intake during pregnancy can produce a wide range of adverse effects on
      nervous system development including fetal alcohol syndrome (FAS). The most
      severe congenital malformation observed in newborns with FAS is cyclopia. In this
      study, we have exposed zebrafish embryos to different ethanol concentrations
      (2.4%, 1.5% or 1.0%) during eye morphogenesis in four zebrafish strains (AB, EK,
      GL and TL). In addition, we have studied the survival rate of the cyclopic
      animals to the end of larval development. The zebrafish strains GL and AB
      generated the higher percentage of cyclopic animals after exposure to 2.4%
      ethanol, while EK showed the higher percent cyclopic animals using 1.5% and 1.0%
      ethanol. The EK strain showed the higher percent survival during the larval
      period at all ethanol concentrations (2.4%, 1.5% and 1.0%). Moreover, we have
      investigated cytoarchitectural alterations in the main components of the visual
      pathway-retina and optic tectum-and ethanol treatment affects both the retina and
      the optic tectum. The lamination of neural retina is clearly delayed in treated
      larvae 3 days postfertilization and the thickness of the pigmented epithelium is
      considerably reduced. With regard to the optic tectum, treatment with ethanol
      alters the normal pattern of tectal lamination. The use of zebrafish EK strain is
      a suitable in vivo vertebrate model system for analyzing the teratogenic effect
      of ethanol during vertebrate visual system morphogenesis as it relates to both
      cyclopia and FAS.

PMID- 16574377
TI  - Differential regulation of Pyk2 phosphorylation at Tyr-402 and Tyr-580 in
      intestinal epithelial cells: roles of calcium, Src, Rho kinase, and the
      cytoskeleton.
AB  - The calcium-dependent proline-rich tyrosine kinase Pyk2 is activated by tyrosine
      phosphorylation, associates with focal adhesion proteins, and has been linked to
      proliferative and migratory responses in a variety of mesenchymal and epithelial
      cell types. Full Pyk2 activation requires phosphorylation at functionally
      distinct sites, including autophosphorylation site Tyr-402 and catalytic domain
      site Tyr-580, though the mechanisms involved are unclear. The pathways mediating
      Pyk2 phosphorylation at Tyr-402 and Tyr-580 were therefore investigated. Both
      sites were rapidly and transiently phosphorylated following cell stimulation by
      Ang II or LPA. However, only Tyr-580 phosphorylation was rapidly enhanced by
      intracellular Ca(2+) release, or inhibited by Ca(2+) depletion. Conversely, Tyr
      402 phosphorylation was highly sensitive to inhibition of actin stress fibers, or
      of Rho kinase (ROK), an upstream regulator of stress fiber assembly. Ang II also
      induced a delayed (30-60 min) secondary phosphorylation peak occurring at Tyr-402
      alone. Unlike the homologous focal adhesion kinase (FAK), Pyk2 phosphorylation
      was sensitive neither to the Src inhibitor PP2, nor to truncation of its N
      terminal region, which contains a putative autoinhibitory FERM domain. These
      results better define the mechanisms involved in Pyk2 activation, demonstrating
      that autophosphorylation is ROK- and stress fiber-dependent, while
      transphosphorylation within the kinase domain is Ca(2+)-dependent and Src
      independent in intestinal epithelial cells. This contrasts with the tight
      sequential coupling of phosphorylation seen in FAK activation, and further
      underlines the differences between these closely related kinases.

PMID- 16574378
TI  - CXCL12 and C5a trigger cell migration via a PAK1/2-p38alpha MAPK-MAPKAP-K2-HSP27
      pathway.
AB  - Cell migration is critical for many processes, such as angiogenesis,
      inflammation, development and wound healing, and is also involved in tumour
      progression and metastasis. Here we show that CXCL12, complement factor 5a (C5a),
      hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF)-BB,
      which stimulate cell migration, also activate p38alpha MAPK. Pharmacological
      inhibition of this protein kinase with SB 203580 or BIRB 0796, or the genetic
      ablation of p38alpha MAPK, blocked cell migration induced by the aforementioned
      chemo-attractants. Macrophages from mice lacking one or more of the other p38
      MAPK isoforms showed normal cell migration in response to C5a. We also show that
      the activation of p38alpha MAPK in response to CXCL12 requires the p21-activated
      protein kinases (PAK)-1 and PAK-2. MAPKAP-K2 is a protein kinase that is
      activated by p38alpha MAPK. Reducing its expression using RNA interference
      blocked CXCL12-induced HeLa cell migration, while macrophages from mice that do
      not express MAPKAP-K2 failed to migrate in response to C5a. Moreover, RNA
      interference against the small heat shock protein 27 (HSP27), a physiological
      substrate of MAPKAP-K2, blocked the CXCL12-induced cell migration. These results
      demonstrate a general and essential role of the PAK-p38alpha MAPK-MAPKAP-K2-HSP27
      signalling pathway in mediating the effects of chemotactic stimuli on cell
      migration.

PMID- 16574379
TI  - Mucocutaneous leishmaniasis: report of a case with massive involvement of nasal,
      pharyngeal and laryngeal mucosa.

PMID- 16574380
TI  - Camptothecin-mediated apoptosis and antiproliferation effect is accompanied by
      down-regulation of telomerase activity in HaCaT cells.

PMID- 16574381
TI  - Identification of two putative rickettsial adhesins by proteomic analysis.
AB  - The rickettsial membrane proteins that promote their uptake by eukaryotic host
      cells are unknown. To identify rickettsial ligand(s) that bind host cell surface
      proteins, biotinylated epithelial cells were used to probe a nitrocellulose
      membrane containing rickettsial extracts separated by SDS-PAGE. This overlay
      assay revealed that two close rickettsial ligands of approximately 32-30 kDa were
      recognized by host cells. Both proteins were identified using high resolution 2D
      PAGE coupled with mass spectrometry analysis. One protein was identified as the C
      terminal extremity of rOmpB called the beta-peptide. The second interacting
      protein was identified as a protein of unknown function encoded by RC1281 and
      RP828 in Rickettsia conorii and in Rickettsia prowazekii, respectively, that
      shares strong similarities with other bacterial adhesins. Both proteins are
      highly conserved within the Rickettsia genus and might play a critical role in
      their pathogenicity. These data may have important implications for the
      development of future vaccines against rickettsial infections.

PMID- 16574382
TI  - The progesterone metabolite allopregnanolone potentiates GABA(A) receptor
      mediated inhibition of 5-HT neuronal activity.
AB  - The dorsal raphe nucleus (DRN) is the origin of much of the 5-HT innervation of
      the forebrain. The activity of DRN 5-HT neurons is regulated by a number of
      receptors including GABA(A) and 5-HT(1A) inhibitory receptors and by excitatory
      alpha(1)-adrenoceptors. Using in vitro electrophysiological recording we
      investigated the action of progesterone and its metabolite, allopregnanolone on
      receptor-mediated responses of DRN 5-HT neurons. Neither allopregnanolone nor
      progesterone affected the alpha(1)-adrenoceptor agonist-induced firing.
      Allopregnanolone also had no effect on the inhibitory response to 5-HT. However,
      allopregnanolone significantly potentiated the inhibitory responses to GABA(A)
      receptor agonists. Progesterone did not enhance GABA(A) receptor-meditated
      inhibitory responses. Thus, the neuroactive metabolite of progesterone,
      allopregnanolone, has the ability to cause potentiation of GABA(A)-mediated
      inhibition of DRN 5-HT neurons. This effect on 5-HT neurotransmission may have
      relevance for mood disorders commonly associated with reproductive hormone
      events, such as premenstrual dysphoric disorder and postpartum depression.

PMID- 16574383
TI  - The decrease of NAD(P)H has a prominent role in dopamine toxicity.
AB  - We characterized dopamine toxicity in human neuroblastoma SH-SY5Y cells as a
      direct effect of dopamine on cell reductive power, measured as NADH and NADPH
      cell content. In cell incubations with 100 or 500 microM dopamine, the
      accumulation of dopamine inside the cell reached a maximum after 6 h. The
      decrease in cell viability was 40% and 75%, respectively, after 24 h, and was not
      altered by MAO inhibition with tranylcypromine. Dopamine was metabolized to DOPAC
      by mitochondrial MAO and, at 500 microM concentration, significantly reduced
      mitochondrial potential and oxygen consumption. This DA concentration caused only
      a slight increase in cell peroxidation in the absence of Fe(III), but a dramatic
      decrease in NADH and NADPH cell content and a concomitant decrease in total cell
      NAD(P)H/NAD(P)+ and GSH/GSSG and in mitochondrial NADH/NAD+ ratios.
      Dopaminechrome, a product of dopamine oxidation, was found to be a MAO-A
      inhibitor and a strong oxidizer of NADH and NADPH in a cell-free system. We
      conclude that dopamine may affect NADH and NADPH oxidation directly. When the
      intracellular concentrations of NAD(P)H and oxidized dopamine are similar,
      NAD(P)H triggers a redox cycle with dopamine that leads to its own consumption.
      The time-course of NADH and NADPH oxidation by dopamine was assessed in cell-free
      assays: NAD(P)H concentration decreased at the same time as dopamine oxidation
      advanced. The break in cell redox equilibrium, not excluding the involvement of
      free oxygen radicals, could be sufficient to explain the toxicity of dopamine in
      dopaminergic neurons.

PMID- 16574384
TI  - GAPDH as a sensor of NO stress.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a classic glycolytic enzyme,
      and accumulating evidence has suggested that GAPDH is a multi-functional protein.
      In particular, its role as a mediator for cell death has been highlighted. For
      the last decade, many groups reported that a pool of GAPDH translocates to the
      nucleus under a variety of stressors, most of which are associated with oxidative
      stress. At the molecular level, sequential steps lead to nuclear translocation of
      GAPDH during cell death as follows: first, a catalytic cysteine in GAPDH (C150 in
      rat GAPDH) is S-nitrosylated by nitric oxide (NO) that is generated from
      inducible nitric oxide synthase (iNOS) and/or neuronal NOS (nNOS); second, the
      modified GAPDH becomes capable of binding with Siah1, an E3 ubiquitin ligase, and
      stabilizes it; third, the GAPDH-Siah protein complex translocates to the nucleus,
      dependent on Siah1's nuclear localization signal, and degrades Siah1's substrates
      in the nucleus, which results in cytotoxicity. A recent report suggests that
      GAPDH may be genetically associated with late-onset of Alzheimer's disease. (-)
      deprenyl, which has originally been used as a monoamine oxidase inhibitor for
      Parkinson's disease, binds to GAPDH and displays neuroprotective actions, but its
      molecular mechanism is still unclear. The NO/GAPDH/Siah1 death cascade will
      contribute to the molecular understanding of a role of GAPDH in neurodegenerative
      disorders and help to establish novel therapeutic strategies.

PMID- 16574385
TI  - A reduction-triggered delivery by a liposomal carrier possessing membrane
      permeable ligands and a detachable coating.
AB  - To control the cellular uptake of drugs and genes, we synthesized a liposomal
      carrier possessing membrane-permeable ligands and a detachable poly(ethylene
      glycol) (PEG) coating. For the detachable coating, a lipid having a thiolytic
      cleavable spacer (PEG-S-S-DOPE) was synthesized by the reaction of
      dioleoylphosphatidylethanolamine (DOPE) with a PEG chain via a disulfide linkage.
      The liposomes were prepared from a mixture of dipalmitoylphosphatidylcholine
      (DPPC), DOPE, PEG-S-S-DOPE, and cholesteryl hemisuccinate (CHEMS). The octamer
      (R8 peptide) of arginine was chosen as the membrane-permeable ligand and
      covalently immobilized onto the CHEMS portion of the liposome surface (PEG-S-S-R8
      liposome). The disulfide bond of the PEG chain was cleaved to display the R8
      peptides on the liposome surface by adding a reducing agent such as L-cysteine,
      and thereby internalization of the liposomes was significantly facilitated. When
      L-cysteine was added to the mixture of cells and the liposome that incorporated
      plasmids encoding the enhanced green fluorescence protein (pEGFP), the expression
      of EGFP was low but could be observed in almost 100% of the cells.

PMID- 16574386
TI  - Kinetic analysis of myocardial uptake and negative inotropic effect of amiodarone
      in rat heart.
AB  - The distribution kinetics of the highly lipophilic antiarrhythmic agent
      amiodarone is not well understood. The purpose of the present investigation was
      to develop a pharmacokinetic-pharmacodynamic (PK/PD) model to describe cardiac
      uptake and the negative inotropic effect of amiodarone in the isolated perfused
      rat heart. Amiodarone (10 microM) was infused for 15 min to 6 hearts. The time
      course of outflow concentration and left ventricular developed pressure were
      measured and analyzed by the model. The uptake of amiodarone by the heart was
      flow limited and characterized by an extremely high partition coefficient with a
      predicted tissue washout half-live of 17 h. Only 36.8% of input amount to heart
      recovered within 45 min after start of the 15 min infusion. The negative
      inotropic effect was delayed with a time constant of 11 min and the maximal
      decrease in left ventricular developed pressure was described by a sigmoid E(max)
      model with an E(max) of 37.7% and an EC(50) of 0.53 microM. Our results suggest a
      rapid tissue uptake and a moderate negative inotropic effect of amiodarone after
      intravenous injection.

PMID- 16574387
TI  - Paclitaxel modifies the accumulation of tumor-diagnostic tracers in different
      ways in P-glycoprotein-positive and negative cancer cells.
AB  - AIM: To study how paclitaxel treatment modifies the accumulation of tumor
      diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer
      cells. METHODS: The accumulations of different P-gp substrates, including
      rhodamine 123, daunorubicin and [(99m)Tc]hexakis-2-methoxybutyl isonitrile
      ((99m)Tc-MIBI), were measured in P-gp-positive (A2780AD) and P-gp-negative human
      ovarian carcinoma cells (A2780) and JY human lymphoid B cells. The uptakes of the
      tumor-diagnostic tracers (11)C-choline and 2-[(18)F]fluoro-2-deoxy-d-glucose
      ((18)FDG) were measured in the same cell lines. The P-gp expression and function
      were demonstrated by flow-cytometry. RESULTS: The (18)FDG measurements revealed
      that the glucose metabolic rate was significantly higher (p<0.01) in the P-gp
      positive A2780AD cells than in the P-gp-negative cells. Paclitaxel (1-70microM)
      increased the (18)FDG uptake (up to 200%) of both P-gp-positive and P-gp-negative
      cells, whereas it did not modulate their (11)C-choline uptake. Paclitaxel
      reinstated the (99m)Tc-MIBI accumulation of the A2780AD cells (to 1500% of the
      control) in a concentration-dependent manner, while it increased the uptake of
      the P-gp-negative cells to a lesser extent (to a maximum of 200% of the control).
      CONCLUSION: Paclitaxel modifies the uptake of tumor-diagnostic tracers in both P
      gp-dependent and independent manners. Interpretation of the multifactorial
      effects of paclitaxel may promote a correct in vivo diagnosis of P-gp-positive
      and P-gp-negative tumors.

PMID- 16574388
TI  - Potential for plant growth promotion in groundnut (Arachis hypogaea L.) cv. ALR-2
      by co-inoculation of sulfur-oxidizing bacteria and Rhizobium.
AB  - The use of Rhizobium inoculant for groundnut is a common practice in India. Also,
      co-inoculation of Rhizobium with other plant growth-promoting bacteria received
      considerable attention in legume growth promotion. Hence, in the present study we
      investigated effects of co-inoculating the sulfur (S)-oxidizing bacterial strains
      with Rhizobium, a strain that had no S-oxidizing potential in groundnut.
      Chemolithotrophic S-oxidizing bacterial isolates from different sources by
      enrichment isolation technique included three autotrophic (LCH, SWA5 and SWA4)
      and one heterotrophic (SGA6) strains. All the four isolates decreased the pH of
      the growth medium through oxidation of elemental S to sulfuric acid.
      Characterization revealed that these isolates tentatively placed into the genus
      Thiobacillus. Clay-based pellet formulation (2.5 x 10(7) cf ug(-1) pellet) of the
      Thiobacillus strains were developed and their efficiency to promote plant growth
      was tested in groundnut under pot culture and field conditions with S-deficit
      soil. Experiments in pot culture yielded promising results on groundnut
      increasing the plant biomass, nodule number and dry weight, and pod yield. Co
      inoculation of Thiobacillus sp. strain LCH (applied at 60 kg ha(-1)) with
      Rhizobium under field condition recorded significantly higher nodule number,
      nodule dry weight and plant biomass 136.9 plant(-1), 740.0mg plant(-1) and 15.0 g
      plant(-1), respectively, on 80 days after sowing and enhanced the pod yield by
      18%. Also inoculation of S-oxidizing bacteria increased the soil available S from
      7.4 to 8.43 kg ha(-1). These results suggest that inoculation of S-oxidizing
      bacteria along with rhizobia results in synergistic interactions promoting the
      yield and oil content of groundnut, in S-deficit soils.

PMID- 16574389
TI  - Efficacy and safety of iodopovidone in chemical pleurodesis: a meta-analysis of
      observational studies.
AB  - The search for an 'ideal' agent for pleurodesis continues. Iodopovidone is a
      topical antiseptic and has been shown to be safe and effective in many studies.
      The aim of this study was to evaluate the efficacy and safety of iodopovidone as
      an agent for chemical pleurodesis. We performed a systematic review of all the
      observational trials which have used iodopovidone for chemical pleurodesis. Six
      studies including 265 patients who had undergone chemical pleurodesis with
      iodopovidone were included for this analysis. Iodopovidone was used for variety
      of indications, which included pleural effusion (157 patients), and pneumothorax
      (108 patients). Pleurodesis was performed through tube thoracostomy in 144
      patients and through thoracoscopy in 121 patients. The success rate of
      pleurodesis varied from 64.2% to 100%, and summary success rate of all the
      studies was 90.6% (95% confidence intervals [CI], 86.4-93.8). The success rate
      was independent for the procedure (tube thoracostomy [126/144; 87.5%, 95% CI 80.9
      92.4] or thoracoscopy [114/121; 94.2%, 95% CI 88.4-97.6]) used for performing
      pleurodesis or for the indication (pleural effusion [139/157; 88.5%, 95% CI 82.5
      93.1] or pneumothorax [101/108; 93.5%, 95% CI 87.1-97.4]). The only significant
      complication reported was chest pain of varying degree. Systemic hypotension was
      reported in three patients in only one study. There were no deaths related to
      chemical pleurodesis with iodopovidone. Overall, this review supports the safety
      and efficacy of iodopovidone as an agent for chemical pleurodesis in cases of
      recurrent pleural effusions and pneumothoraces regardless of their etiology.

PMID- 16574390
TI  - The expression of pro- and anti-apoptotic Bcl-2 family proteins in
      peribronchiolar lymphocytes from patients with diffuse panbronchiolitis.
AB  - Diffuse panbronchiolitis (DPB) is a distinctive form of small airway disease,
      which is characterized by chronic inflammation with lymphocyte infiltration
      around bronchioles. The aim of this study was to evaluate the importance of
      factors related to apoptosis in peribronchiolar lymphocytes of DPB. We employed
      immunohistochemical methods for the localization of Bax (a promoter of
      apoptosis), Bcl-2 (an inhibitor of apoptosis), and caspase-3 (a key executioner
      molecule of apoptosis) in lung tissues of five patients with DPB. In all
      patients, immunostaining for Bax was almost completely absent in accumulated
      lymphocytes around the bronchioles and in lymphocytes of the parafollicular area
      that correspond to a zone populated by T cells. In contrast to the reaction for
      Bax, Bcl-2 immunoreactivity was uniformly strong in all of the patients. The
      pattern of staining for caspase-3 was similar to that for Bax in all of the
      patients. In normal lung tissue, a few lymphocytes showed negative immunostaining
      for Bcl-2 and a positive reaction for caspase-3. Our results suggest that Bcl-2
      protein may provide T-lymphocyte survival and hypercellularity in the
      bronchioles, thereby contributing to the progression of DPB.

PMID- 16574391
TI  - Chromatin remodelling and transcription: be-WICHed by nuclear myosin 1.
AB  - Transcription in eukaryotic cells requires dynamic changes of chromatin structure
      to facilitate or prevent RNA polymerase access to active genes. These structural
      modifications rely on the concerted action of ATP-dependent chromatin-remodelling
      complexes and histone-modifying enzymes, which generate a chromatin configuration
      that is either compatible with transcription (euchromatin) or incompatible
      (heterochromatin). Insights into how these structural changes might be
      coordinated for RNA polymerase I (pol I) genes come from the discoveries of the
      nucleolar-remodelling complex (NoRC) and B-WICH--a high molecular weight fraction
      of the WSTF/SNF2h chromatin-remodelling complex. NoRC produces a repressive
      chromatin state; B-WICH, together with nuclear myosin 1, activates pol I
      transcription directly on chromatin templates and might also function in the
      maintenance of ribosomal chromatin structure.

PMID- 16574392
TI  - Cement/clay interactions-- a review: experiments, natural analogues, and
      modeling.
AB  - The concept of storing radioactive waste in geological formations calls for large
      quantities of concrete that will be in contact with the clay material of the
      engineered barriers as well as with the geological formation. France, Switzerland
      and Belgium are studying the option of clayey geological formations. The clay and
      cement media have very contrasted chemistries that will interact and lead to a
      degradation of both types of material. The purpose of this review is to establish
      an exhaustive list of laboratory experiments so as to identify the reaction
      sequences in the evolution of both the clay minerals and accessory minerals
      during their alteration in an alkaline environment. We review the data on clay
      dissolution kinetics in this environment, and include an invaluable study of
      natural analogues that allow one to correlate the phenomena in time. The
      available data and experiments make it possible to construct predictive numerical
      models. However, as the quality of the data is inhomogeneous, we recommend a
      continuation of the thermodynamic and kinetic data acquisition. It is obvious
      that the numerical modeling of the alkaline disturbance will be more relevant if
      it can combine the advantages of the different detailed models: mineralogical
      completeness, combined modeling of the clay and cement media, evolution of the
      porosity, consideration of the pCO2 and all the surface reactions.

PMID- 16574393
TI  - Chemical-mineralogical characterisation of coarse recycled concrete aggregate.
AB  - The construction industry is now putting greater emphasis than ever before on
      increasing recycling and promoting more sustainable waste management practices.
      In keeping with this approach, many sectors of the industry have actively sought
      to encourage the use of recycled concrete aggregate (RCA) as an alternative to
      primary aggregates in concrete production. The results of a laboratory
      experimental programme aimed at establishing chemical and mineralogical
      characteristics of coarse RCA and its likely influence on concrete performance
      are reported in this paper. Commercially produced coarse RCA and natural
      aggregates (16-4 mm size fraction) were tested. Results of X-ray fluorescence
      (XRF) analyses showed that original source of RCA had a negligible effect on the
      major elements and a comparable chemical composition between recycled and natural
      aggregates. X-ray diffraction (XRD) analyses results indicated the presence of
      calcite, portlandite and minor peaks of muscovite/illite in recycled aggregates,
      although they were directly proportioned to their original composition. The
      influence of 30%, 50%, and 100% coarse RCA on the chemical composition of equal
      design strength concrete has been established, and its suitability for use in a
      concrete application has been assessed. In this work, coarse RCA was used as a
      direct replacement for natural gravel in concrete production. Test results
      indicated that up to 30% coarse RCA had no effect on the main three oxides (SiO2,
      Al2O3 and CaO) of concrete, but thereafter there was a marginal decrease in SiO2
      and increase in Al2O3 and CaO contents with increase in RCA content in the mix,
      reflecting the original constituent's composition.

PMID- 16574394
TI  - Movement of unlined landfill under preloading surcharge.
AB  - As organic solid waste is decomposed in a landfill and mass is lost due to gas
      and leachate formation, the landfill settles. Settlement of a landfill interferes
      with the rehabilitation and subsequent use of the landfill site after closure.
      This study examined the soil/solid waste movement at the Al-Qurain landfill in
      Kuwait after 15 years of closure as plans are underway for redevelopment of the
      landfill site that occupies about a km(2) with an average depth of 8-15m. Field
      experiments were conducted for 6 mo to measure soil/solid waste movement and
      water behavior within the landfill using two settlement plates with a level
      survey access, Casagrande-type piezometers, pneumatic piezometers, and magnetic
      probe extensometers. Previous results obtained indicated that biological
      decomposition of refuse continued after closure of the landfill site. The
      subsurface water rise enhanced the biological activities, which resulted in the
      production of increasing quantities of landfill gas. The refuse fill materials
      recorded a high movement rate under the imposed preloading as a result of an
      increase in the stress state. Up to 55% of the total movement was observed during
      the first 2 weeks of fill placement and increased to 80% within the first month
      of the 6-mo preloading test. Pneumatic piezometers showed an increase in water
      head, which is attributed to the developed pressure of gases escaping during the
      preloading period.

PMID- 16574395
TI  - Continuous monitoring of odours from a composting plant using electronic noses.
AB  - The odour impact of a composting plant situated in an urbanized area was
      evaluated by continuously monitoring the ambient air close to the plant during a
      period of about 4 days using two electronic noses. One electronic nose was
      installed in a nearby house, and the other one inside the perimeter of the
      composting plant in order to compare the response of both instruments. The
      results of the monitoring are represented by tables that report the olfactory
      class and the odour concentration value attributed to the analyzed air for each
      of the 370 measurements carried out during the monitoring period. The electronic
      nose installed at the house detected the presence of odours coming from the
      composting plant for about 7.8% of the monitoring total duration. Of the odour
      detections, 86% (25 of 29 measurements) were classified as belonging to the
      olfactory class corresponding to the open air storage of the waste screening
      overflows heaps, which was therefore identified to be the major odour source of
      the monitored composting plant. In correspondence of the measurements during
      which the electronic nose inside the house detected the presence of odours from
      the composting plant, the olfactory classes recognized by both instruments
      coincide. Moreover, the electronic nose at the house detected the presence of
      odours from the composting plant at issue in correspondence of each odour
      perception of the house occupants. The results of the study show the possibility
      of using an electronic nose for environmental odours monitoring, which enables
      the classification of the quality of the air and to quantify the olfactory
      nuisance from an industrial source in terms of duration and odour concentration.

PMID- 16574396
TI  - Treatment of a high-strength sulphate-rich alkaline leachate using an anaerobic
      filter.
AB  - The research looks at the feasibility of treating an alkaline sulphate-rich
      leachate arising from the co-disposal of municipal solid waste with cement kiln
      dust by means of an anaerobic filter (AF). This type of leachate with a high
      sulphate concentration is commonly prohibited for discharge to sewer and requires
      an on-site treatment solution. The AF used had a working volume of 4l and
      contained reticulated polyurethane foam as the biomass support material. The
      filters were operated over a 152 day experimental period during which the COD
      loading onto the filter was increased from 0.76 to 7.63kgCODm(-3)d(-1). In the
      early stages of operation at low loading, soluble sulphides accumulated that
      inhibited methanogenic activity. This was restored by dosing FeCl(3) to the
      reactor. The continued dosing allowed efficient COD removal of between 75% and
      90% until the nominal retention time in the reactor was 3 days, at which point
      reactor performance declined significantly. The main mechanism for COD removal
      was by sulphate-reducing bacteria, which also resulted in up to 88% sulphate
      removal from the leachate. The average methane generation rate was 0.10lg(-1) COD
      removed. The results indicate the potential for using this approach as a pre
      treatment that could significantly reduce the COD load to a second stage
      treatment process, but problems associated with the implementation of the
      technology at a larger scale have been identified.

PMID- 16574397
TI  - DNA hybridization detection on electrical microarrays using coulostatic pulse
      technique.
AB  - We demonstrated a novel application of transient coulostatic pulse technique for
      the detection of label free DNA hybridization on nm-sized gold interdigitated
      ultramicroelectrode arrays (Au-IDA) made in silicon technology. The array
      consists of eight different positions with an Au-IDA pair at each position
      arranged on the Si-based Biochip. Immobilization of capture probes onto the Au
      IDA was accomplished by self-assembling of thiol-modified oligonucleotides.
      Target hybridization was indicated by a change in the magnitude of the time
      dependant potential relaxation curve in presence of electroactive Fe(CN)(6)(3-)
      in the phosphate buffer solution. While complementary DNA hybridization showed
      50% increase in the relaxation potential, the non-complementary DNA showed a
      negligible change. A constant behaviour was noted for all positions. The dsDNA
      specific intercalating molecule, methylene blue, was found to be enhancing the
      discrimination effect. The changes in the relaxation potential curves were
      further corroborated following the ELISA like experiments using ExtraAvidine
      alkaline phosphatase labelling and redox recycling of para-aminophenol phosphate
      at IDAs. The coulostatic pulse technique was shown to be useful for identifying
      DNA sequences from brain tumour gene CK20, human herpes simplex virus,
      cytomegalovirus, Epstein-Barr virus and M13 phage. Compared to the hybridization
      of short chain ONTs (27 mers), the hybridization of long chain M13 phage DNA
      showed three times higher increase in the relaxation curves. The method is fast
      enough to monitor hybridization interactions in milli or microsecond time scales
      and is well suitable for miniaturization and integration compared to the common
      impedance techniques for developing capacitative DNA sensors.

PMID- 16574398
TI  - Supported imprinted nanospheres for the selective recognition of cholesterol.
AB  - The preparation of innovative polymeric systems using molecular imprinting
      technology for application in extracorporeal blood purification is described.
      Membranes based on a methylmethacrylate-co-acrylic acid copolymer, produced
      through the phase inversion method, were modified introducing into their
      structure specific binding sites for cholesterol molecule by adding molecularly
      imprinted nanoparticles in the membrane matrix. Membranes prepared are intended
      to selectively remove cholesterol from the blood by using interactions at a
      molecular level, between the membrane/nanoparticles devices and the template,
      created during the preparation of polymers. Three polymeric systems in form of
      nanoparticles were prepared differing in the polymerisation solvent (a mixture of
      acetonitrile and ethanol (1:1) or pure ethanol), and the molar ratio between the
      functional monomer and the cross-linker (2.3:1 and 1:1). Two out of three of the
      prepared polymers showed a very good template rebinding capacity both in
      phosphate buffer solution (pH 6.9) and in ethanol. In particular the
      nanoparticles rebound 115.4 mg cholesterol/g polymer in buffer solution, and 57
      mg cholesterol/g polymer in ethanol. The deposition of the nanoparticles on the
      surface of the phase inversion membranes produced devices with interesting
      rebinding performances towards cholesterol in buffer solution: a specific
      recognition of 14.09 mg cholesterol/g system (membrane and nanoparticles) was
      detected, indicating maintained binding capacity of supported particles as well.

PMID- 16574399
TI  - Experimental and theoretical analysis of neuron-transistor hybrid electrical
      coupling: the relationships between the electro-anatomy of cultured Aplysia
      neurons and the recorded field potentials.
AB  - Understanding the mechanisms that generate field potentials (FPs) by neurons
      grown on semiconductor chips is essential for implementing neuro-electronic
      devices. Earlier studies emphasized that FPs are generated by current flow
      between differentially expressed ion channels on the membranes facing the chip
      surface, and those facing the culture medium in electrically compact cells. Less
      is known, however, about the mechanisms that generate FPs by action potentials
      (APs) that propagate along typical non-isopotential neurons. Using Aplysia
      neurons cultured on floating gate-transistors, we found that the FPs generated by
      APs in cultured neurons are produced by current flow along neuronal compartments
      comprising the axon, cell body, and neurites, rather than by flow between the
      membrane facing the chip substrate and that facing the culture medium. We
      demonstrate that the FPs waveform generated by non-isopotential neurons largely
      depends on the morphology of the neuron.

PMID- 16574400
TI  - Harvesting energy from the marine sediment-water interface II. Kinetic activity
      of anode materials.
AB  - Here, we report a comparative study on the kinetic activity of various anodes of
      a recently described microbial fuel cell consisting of an anode imbedded in
      marine sediment and a cathode in overlying seawater. Using plain graphite anodes,
      it was demonstrated that a significant portion of the anodic current results from
      oxidation of sediment organic matter catalyzed by microorganisms colonizing the
      anode and capable of directly reducing the anode without added exogenous electron
      transfer mediators. Here, graphite anodes incorporating microbial oxidants are
      evaluated in the laboratory relative to plain graphite with the goal of
      increasing power density by increasing current density. Anodes evaluated include
      graphite modified by adsorption of anthraquinone-1,6-disulfonic acid (AQDS) or
      1,4-naphthoquinone (NQ), a graphite-ceramic composite containing Mn2+ and Ni2+,
      and graphite modified with a graphite paste containing Fe3O4 or Fe3O4 and Ni2+.
      It was found that these anodes possess between 1.5- and 2.2-fold greater kinetic
      activity than plain graphite. Fuel cells were deployed in a coastal site near
      Tuckerton, NJ (USA) that utilized two of these anodes. These fuel cells generated
      ca. 5-fold greater current density than a previously characterized fuel cell
      equipped with a plain graphite anode, and operated at the same site.

PMID- 16574401
TI  - EORTC consensus recommendations for the treatment of mycosis fungoides/Sezary
      syndrome.
AB  - Several reviews and guidelines on the management of mycosis fungoides and Sezary
      syndrome (MF/SS) have been published; however, treatment strategies for patients
      with MF/SS vary from institution to institution and no European consensus has yet
      been established. There are few phase III trials to support treatment decisions
      for MF/SS and treatment is often determined by institutional experience. In order
      to summarise the available evidence and review 'best practices' from each
      national group, the European Organisation for Research and Treatment of Cancer
      (EORTC) Cutaneous Lymphoma Task Force met in September 2004 to establish European
      guidelines for the treatment of MF/SS. This article reviews the treatment
      regimens selected for inclusion in the guidelines and summarises the clinical
      data for treatments appropriate for each stage of MF/SS. Guideline
      recommendations are presented according to the quality of supporting data, as
      defined by the Oxford Centre for Evidence-Based Medicine. Skin-directed therapies
      are the most appropriate option for early-stage MF/SS and most patients can look
      forward to a normal life expectancy. Patients with advanced disease should be
      encouraged to participate in clinical trials and maintenance of quality of life
      should be paramount.

PMID- 16574402
TI  - Inhibiting myosin light chain kinase retards the growth of mammary and prostate
      cancer cells.
AB  - We have previously shown that ML-7, which inhibits myosin light chain kinase
      (MLCK), induces apoptosis in transformed and non-transformed cells. We have
      extended these studies and found that ML-7 stimulates the ability of etoposide to
      induce apoptosis in Mm5MT mouse mammary adenocarcinoma cells and Mat-Ly-Lu rat
      prostate cancer cells in vitro. ML-7 was also found to have a chemopreventive
      effect using an in vitro mouse mammary organ culture model. In vivo experiments
      demonstrated that ML-7 retards the growth of mammary tumours in mice and prostate
      tumours in rats. Moreover, ML-7 significantly stimulates the ability of etoposide
      to prevent the growth of established mammary tumours in mice and prostate tumours
      in rats. These results provide evidence for the efficacy of ML-7 as an adjuvant
      to etoposide in these models and warrants further development.

PMID- 16574403
TI  - Survival of non-seminomatous germ cell cancer patients according to the IGCC
      classification: An update based on meta-analysis.
AB  - The International Germ Cell Consensus (IGCC) Classification distinguishes
      patients with non-seminomatous germ cell tumours (NSGCT) with a good,
      intermediate or poor prognosis, with a reported 5-year overall survival of 92%,
      80% and 48%, respectively. Since the IGCC classification was based on patients
      treated between 1975 and 1990, we aimed to investigate whether survival has
      improved for more recently treated patients. We did a systematic search of the
      literature and included studies on survival of patients with NSGCT, treated after
      1989 and classified according to the IGCC classification. Survival estimates of
      selected studies were pooled using meta-analytic techniques. We included 10
      papers, describing 1775 patients with NSGCT with good (n = 1087), intermediate (n
      = 232), or poor (n = 456) prognosis. Pooled 5-year survival estimates were 94%,
      83% and 71%, respectively. Since the publication of the IGCC classification,
      there was a small increase in survival for good and intermediate prognosis
      patients, and a large increase in survival for patients with a poor prognosis.
      This increase is most likely due to both more effective treatment strategies and
      more experience in treating NSGCT patients.

PMID- 16574404
TI  - Association between diabetes mellitus and adverse characteristics of breast
      cancer at presentation.
AB  - Type 2 diabetes mellitus is associated with increased incidence and inferior
      outcome of various malignancies. The aim of this study was to explore the impact
      of type 2 diabetes on breast cancer characteristics at presentation. The study
      population included 79 diabetic and 158 age-matched non-diabetic patients.
      Parity, country of birth, co-morbidity other than diabetes, and mode of diagnosis
      were similar in both groups. Mean body mass index (BMI) was higher among diabetic
      patients. Tumour stage and size were higher among diabetic patients and the
      differences remained significant after adjustment for BMI. Moreover, after
      adjustment for BMI, breast cancer among diabetic patients was more often hormone
      receptor negative. Our results show that diabetes mellitus is associated with
      negative prognostic factors at breast cancer presentation.

PMID- 16574405
TI  - SF-1 overexpression in childhood adrenocortical tumours.
AB  - The steroidogenic factor 1 (SF-1) gene encodes a transcription factor playing a
      pivotal role in the regulation of adrenogenital development. We have recently
      shown that SF-1 is amplified in childhood adrenocortical tumours (ACT). This
      study was aimed to assess if an increase in SF-1 gene copy number was associated
      with increased protein levels and to study the correlation between SF-1
      expression and ACT clinical parameters. An increased SF-1 copy number was
      detected in eight of the 10 ACT cases studied. Conversely, the SF-1 protein was
      found to be overexpressed in all cases, compared to normal age-matched adrenal
      glands. No significant correlation was found between SF-1 protein levels and its
      gene copy number. Furthermore, no significant correlation existed with
      histological grade or with the clinical manifestation or evolution of disease.
      This data show that SF-1 overexpression is widespread in childhood ACT and is
      likely to play a role in its pathogenesis.

PMID- 16574406
TI  - A novel process for extraction of edible oils: Enzyme assisted three phase
      partitioning (EATPP).
AB  - Three phase partitioning (TPP), a technique used in protein purification has been
      evaluated, for extraction of oil from three different plant sources viz: mango
      kernel, soybean and rice bran. The process consists of simultaneous addition of t
      butanol (1:1,v/v) and ammonium sulphate (w/v) to a crude preparation/slurry.
      Under optimized condition, the protein appears as an interfacial precipitate
      between upper t-butanol containing oil and lower aqueous phase. Pretreatment of
      the slurries with a commercial enzyme preparation of proteases, Protizyme,
      followed by three phase partitioning resulted in 98%, 86% and 79% (w/w) oil
      yields in case of soybean, rice bran and mango kernel, respectively. The
      efficiency of the present technique is comparable to solvent extraction with an
      added advantage of being less time consuming and using t-butanol which is a safer
      solvent as compared to n-hexane used in conventional oil extraction process.

PMID- 16574407
TI  - Adsorption mechanism of cadmium on juniper bark and wood.
AB  - In this study the capacity of sorbents prepared from juniper wood (JW) and bark
      (JB) to adsorb cadmium (Cd) from aqueous solutions at different pH values was
      compared. Adsorption behavior was characterized through adsorption kinetics,
      adsorption isotherms, and adsorption edge experiments. Results from kinetics and
      isotherm experiments showed that JB (76.3-91.6 micromol Cdg(-1) substrate) had 3
      4 times higher adsorption capacity for Cd than JW (24.8-28.3 micromol Cdg(-1)).
      In addition to higher capacity, JB exhibited a higher strength of adsorption
      (45.3 versus 9.1 Lmmol(-1)) and faster uptake kinetics (0.0119 versus 0.0083 g
      micromol(-1)min(-1)) compared to JW. For both these adsorbents, increasing Cd
      adsorption with increasing solution pH in the range of 2-6 suggests that surface
      carboxyl groups (RCOOH) might be involved in interaction with Cd. Diffuse
      reflectance infrared Fourier transform (DRIFT) spectra showed that the surface
      concentration of carboxyl groups was higher on JB compared to JW. The ratio of Ca
      released to Cd adsorbed was 1.04 and 0.78 for JB and JW, respectively, indicating
      that Ca-Cd ion-exchange was the primary mechanism involved. The higher Ca content
      in JB (15 times more) and the surface RCOOH concentration (2.5 times more) can be
      attributed to the observed differences in Cd adsorption behavior between the two
      lignocellulosic adsorbents.

PMID- 16574408
TI  - Unpolluted fractionation of wheat straw by steam explosion and ethanol
      extraction.
AB  - An unpolluted process of wheat straw fractionation by steam explosion coupled
      with ethanol extraction was studied. The wheat straw was steam exploded for 4.5
      min with moisture of 34.01%, a pressure of 1.5 MPa without acid or alkali.
      Hemicellulose sugars were recovered by water countercurrent extraction and
      decolored with chelating ion exchange resin D412. The gas chromatography (GC) and
      high-performance liquid chromatography (HPLC) analysis results indicated that
      there were organic acids in the hemicellulose sugars and the ratio of
      monosaccharides to oligosaccharides was 1:9 and the main component, xylose, was
      85.9% in content. The total recovery rate of hemicellulose was 80%. Water washed
      materials were subsequently extracted with ethanol. The optimum extraction
      conditions in this work were 40% ethanol, fiber/liquor ratio 1:50 (w/v), severity
      log(R)=3.657 (180 degrees C for 20 min), 0.1% NaOH. The lignin yield was 75% by
      acid precipitation and 85% ethanol solvent was recovered. The lignin was purified
      using Bjorkman method. Infrared spectrometry (IR) results indicated that the
      lignin belonged to GSH (guaiacyl (G) syringyl (S) and p-hydroxyphenyl (H)) lignin
      and its purity rate reached 85.3%. The cellulose recovery rate was 94% and the
      results of electron spectroscopy for chemical analysis (ESCA) and infrared
      spectrometry (IR) showed that hemicellulose and lignin content decreased after
      steam explosion and ethanol extraction.

PMID- 16574409
TI  - Aerobic biodegradation of alkylphenol ethoxylates.
AB  - Primary aerobic biodegradation of alkylphenol ethoxylates (APEOs) was studied
      using a new simple and fast porphyrin method, which did not require the
      extraction step. Extent of primary biodegradation of a nonylphenol ethoxylates
      (NP-10) was excess of 92% after 1.5 days, and reached 99% after 2 days, which was
      similar to the results obtained using modified CTAS (thiocyanate active
      substances) method. Degradation of benzene ring of NP-10 was studied using UV
      absorbance at 277 nm in chloroform. Results showed that only little of benzene
      ring was degraded.

PMID- 16574410
TI  - Gallic acid and tannase accumulation during fungal solid state culture of a
      tannin-rich desert plant (Larrea tridentata Cov.).
AB  - Larrea tridentata (Sesse & Mocino ex DC.) Coville, also known as Larrea,
      gobernadora, chaparral, or creosote bush, is a shrubby plant which dominates some
      areas of the desert southwest in the United States and Northern Mexico and its
      use has not been exploited and standardized. In this study, gobernadora was
      studied to evaluate its potential use for support of solid state culture.
      Influence of two minimal media added with gobernadora powder as the sole carbon
      source and inducer of tannin-degrading enzymes was evaluated. Cultures were
      initially 70% moisture, had a pH of 5.5 and were inoculated with Aspergillus
      niger Aa-20 at 2 x 10(7) spores per gram of media. Analysis of pH, moisture,
      tannin uptake, gallic acid accumulation and tannase production were evaluated.
      Results indicated a high content of condensed (39.4%dm) and hydrolysable
      (22.8%dm) tannins. Invasion capacity of fungal growth was of 0.15 mmh(-1).
      Tannase production reached values of 1040 Ul(-1) at 43 h of culture. During the
      first 48 h of culture, the concentration of gallic acid accumulation was 0.33 gl(
      1). Gobernadora is a potential source of gallic acid and tannase production by
      solid state culture; however, further optimization of the process is needed.

PMID- 16574411
TI  - Synthesis and evaluation of two 18F-labeled imidazo[1,2-a]pyridine analogues as
      potential agents for imaging beta-amyloid in Alzheimer's disease.
AB  - Two new fluorinated imidazo[1,2-a]pyridine derivatives, 6-(2'-fluoroethyl)-2-(4'
      dimethylamino)phenylimidazo[1,2-a]pyridine (FEPIP) and 6-(3'-fluoropropyl)-2-(4'
      dimethylamino)phenylimidazo[1,2-a]pyridine (FPPIP), were synthesized. The binding
      affinity for FEPIP and FPPIP to amyloid plaques in human AD cortical tissues was
      determined. Radiolabeling, in vitro film autoradiography, and micro-PET study
      were performed with [18F]FPPIP to determine its utility as a radioligand for
      amyloid plaque imaging in the brain of AD patients.

PMID- 16574412
TI  - Osteoblast differentiation stimulating activity of biflavonoids from Cephalotaxus
      koreana.
AB  - Six amentoflavone-type biflavonoids, bilobetin (1), ginkgetin (2), 4',7''-di-O
      methyl-amentoflavone (3), 7-O-methyl-isoginkgetin (4), sciadopitysin (5), and
      7,4',7'',4'''-O-methyl-amentoflavone (6), were isolated from the EtOAc fraction
      of Cephalotaxus koreana Nakai (Cephalotaxaceae) by bioactivity-guided
      fractionation technique using primary cultures of mouse osteoblasts as an in
      vitro assay system. Among the six biflavonoids isolated, bilobetin (1),
      sciadopitysin (5), and 7,4',7'',4'''-O-methyl-amentoflavone (6) significantly
      increased osteoblast differentiation as assessed by alkaline phosphatase
      activity, collagen synthesis, and mineralization. Considering structure-activity
      relationship, methoxyl groups at 4' and 4''' in the B rings in amentoflavone-type
      biflavonoid might be important in osteoblast differentiation. Taken together, our
      present study suggests therapeutic potential of biflavonoids against bone
      diseases such as osteoporosis.

PMID- 16574413
TI  - NK1 antagonists based on seven membered lactam scaffolds.
AB  - A new class of high affinity hNK1R antagonists based on seven-membered ring cores
      has been identified. This series, with relatively simple, compact structures,
      includes compounds with high affinity, good selectivity, and promising in vivo
      properties.

PMID- 16574414
TI  - Quantitative structure-activity relationship studies on HEPTs by supervised
      stochastic resonance.
AB  - Quantitative structure-activity relationship studies (QSAR) on HEPTs were
      performed by using a new approach--supervised stochastic resonance (SSR) in this
      paper. Errors in physicochemical properties have great effects on variable
      selection and the predictive capability of QSAR models but errors-in-variables
      were seldom discussed in QSAR. In this paper, based on the theory of stochastic
      resonance (SR), SSR was proposed and employed to the problem. In SSR, errors and
      abundant variables were regarded as noise and the relevant descriptors as
      signals. In the nonlinear systems involved in the SR, the signal and the noise
      interact harmonically and the signal was consequently enhanced. Therefore, the
      correlation between the relevant variables and a specified activity of a series
      molecule was improved by SSR. It is demonstrated that the obtained QSAR models
      for HEPT analogues by SSR were comparable to those by published methods in their
      stability and predictivity. SSR is an efficient and promising approach to QSAR
      studies.

PMID- 16574415
TI  - Synthesis and biological evaluation of homoserine lactone derived ureas as
      antagonists of bacterial quorum sensing.
AB  - A series of 15 racemic alkyl- and aryl-N-substituted ureas, derived from
      homoserine lactone, were synthesized and tested for their ability to
      competitively inhibit the action of 3-oxohexanoyl-l-homoserine lactone, the
      natural inducer of bioluminescence in the bacterium Vibrio fischeri. N-alkyl
      ureas with an alkyl chain of at least 4 carbon atoms, as well as certain ureas
      bearing a phenyl group at the extremity of the alkyl chain, were found to be
      significant antagonists. In the case of N-butyl urea, it has been shown that the
      antagonist activity was related to the inhibition of the dimerisation of the N
      terminal domain of ExpR, a protein of the receptor LuxR family. Molecular
      modelling suggested that this would result from the formation of an additional
      hydrogen bond in the protein acylhomoserine lactone binding cavity.

PMID- 16574416
TI  - Identification of chemically diverse Chk1 inhibitors by receptor-based virtual
      screening.
AB  - Inhibition of the Chk1 kinase by small molecules is of great therapeutic interest
      for oncology and in understanding the cellular regulation of the G2/M checkpoint.
      We report how computational docking of a large electronic catalogue of compounds
      to an X-ray structure of the Chk1 ATP-binding site allowed prioritisation of a
      small subset of these compounds for assay. This led to the discovery of 10 novel
      Chk1 inhibitors, distributed among nine new and clearly different chemical
      scaffolds. Several of these scaffolds have promising lead-like properties. All
      these ligands act by competitive binding to the targeted ATP site. The crystal
      structures of four of these compounds bound to this site are presented, and
      reasonable modelled docking modes are suggested for the 5 other scaffolds. This
      structural context is used to assess the potential of these scaffolds for further
      medicinal chemistry efforts, suggesting that several of them could be elaborated
      to make additional interactions with the buried part of the ATP site. Some
      unusual interactions with the conserved kinase backbone motif are pointed out.
      The ligand-binding modes are also used to discuss their medicinal chemistry
      potential with respect to undesirable chemical functionalities, whether these
      functionalities bind directly to the protein or not. Overall, this work
      illustrates how virtual screening can identify a diverse set of ligands which
      bind to the targeted site. The structural models for these ligands in the Chk1
      ATP-binding site will facilitate further medicinal chemistry efforts targeting
      this kinase.

PMID- 16574417
TI  - Structure basis for the inhibitory mechanism of a novel DNase gamma-specific
      inhibitor, DR396.
AB  - DNase gamma, a member of the DNase I family, has been suggested to cause DNA
      fragmentation during apoptosis. We recently identified 4-(4,6-dichloro-[1,3,5]
      triazine-2-ylamino)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)-benzoic acid (DR396) as a
      novel specific inhibitor for human DNase gamma [Sunaga, S.; Kobayashi, T.;
      Yoshimori, A.; Shiokawa, D.; Tanuma, S. Biochem. Biophys. Res. Commun.2004, 325,
      1292]. However, the binding mode (coordinate) of DR396 to DNase gamma has not yet
      been defined. Here, we examined the molecular basis for the inhibitory activity
      of DR396 to DNase gamma by structure-based computational docking studies. In the
      blind-docking study using a human DNase gamma homology model, a unique binding
      site of DR396 was predicted, which is tentatively named the 'DNA trapping site'
      because of the binding domain of the unhydrolyzed DNA strand, but not the active
      site. Targeting the DNA trapping site as a hot spot, new human DNase gamma
      inhibitors were obtained from our diverse chemical library in silico. These
      inhibitors showed high correlations between their predicted binding-free energies
      (DeltaGs) and observed IC50 values in the DNA trapping site but not the active
      site. The IC50 of a regioisomer of DR396, 5-(4,6-dichloro-[1,3,5]-triazine-2
      ylamino)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)-benzoic acid (DF365), was 73 microM
      (DeltaG=-9.75 kcal/mol), a 20-fold weaker inhibitory ability than that of DR396
      (IC50=3.2 microM, DeltaG=-11.22 kcal/mol). Fluorescein and triazine derivatives,
      partial structures of DR396, had little inhibitory activity for DNase gamma.
      Docking analyses of the interaction between DR396 and DNase gamma revealed that
      DR396 binds tightly to three subsites (S1, S2, and S3) in the trapping site of
      DNase gamma by forming six hydrogen bonds, whereas DF365 and the partial
      structures are unable to form hydrogen bonds at all three subsites. These
      findings suggest that the specificity and potency of the inhibitory activity of
      DR396 for DNase gamma is due to the specific interaction of DR396 with three
      subsites in the DNA trapping site of DNase gamma.

PMID- 16574418
TI  - Standardization of NIRR-1 irradiation and counting facilities for instrumental
      neutron activation analysis.
AB  - The first nuclear reactor in Nigeria, the Nigeria Research Reactor-1 (NIRR-1), is
      a Miniature Neutron Source Reactor (MNSR). It was specifically acquired for
      elemental analysis by the neutron activation analysis (NAA) technique. In this
      work, routine experimental schemes for the determination of over 30 elements of
      interest in different sample matrices have been developed. In order to validate
      the experimental procedures the following standard reference materials, IAEA-359
      (Cabbage), IAEA-336 (Lichen), GSR-5 and GSD-11 (Chinese Geochemical Rock
      Standards), as well as IAEA-SL-3 and IAEA-405 (Sediments) were analyzed.
      Validated results are presented for the following elements Al, As, Au, Ba, Br,
      Ca, Ce, Cl, Co, Cr, Cs, Cu, Dy, Eu, Fe, Ga, Hf, In, K, La, Lu, Mg, Mn, Na, Rb,
      Sb, Sc, Sm, Ta, Tb, Th, Ti, U, V, Yb and Zn. To further assess analytical
      capabilities of the facilities, the detection limits are presented.

PMID- 16574419
TI  - Calculation of electron deposition in proportional counters.
AB  - Efficiency extrapolation is a common technique in the standardization of
      radionuclides by the technique of 4pibeta-gamma coincidences. It can be achieved
      in two ways: adding thin films onto the radioactive source or by electronic
      discrimination in a pressurized 4pibeta-gamma system. The last case is the most
      extensively used actually in metrology laboratories. There is a need to know the
      electron energy loss inside the proportional counter as a function of the
      electron energies and working pressures. Calculations of electron energy loss
      have been performed for electron energies in a range from a few keV to 2 MeV in a
      mixture of Ar(90%) CH4(10%) and for pressures ranging from 100 to 2000 kPa in a 5
      cm radius proportional counter. Wall effects, such as electron backscattering,
      are included in the calculations. Results are provided in the form of graphs and
      some recommendations are given about the optimal values of the energies that can
      be used to perform the extrapolation in the standardization of some
      radionuclides.

PMID- 16574420
TI  - EC intercomparisons for laboratories monitoring environmental radioactivity.
AB  - International measurement comparisons are organised regularly for EU laboratories
      involved in monitoring radioactivity, with emphasis on meeting routine
      measurement conditions. Using the recent comparison of 137Cs in air filters as an
      example, the whole cycle is described: establishment of traceable reference
      values, spiking of individual filters for the comparison and their quality
      assurance, treatment and measurement of filters in the participating laboratories
      and evaluation of comparison results. The treatment of an individual result,
      deviating widely from the reference value, is discussed. Monte-Carlo simulations
      allow to estimate the maximum errors possibly made due to a non-suitable
      measurement geometry.

PMID- 16574421
TI  - Mean values of the LMM Auger transition in a KLM model.
AB  - The standardization of radionuclides decaying by electron capture can be carried
      out in LS counters by the CIEMAT/NIST method. The KLM model considers a
      simplified atomic rearrangement model in which all L- and M-subshells have been
      averaged. In this paper, instead of considering the 22 rearrangement pathways of
      the KLM model, we concentrate our analysis on the pathways corresponding to L
      Auger electron transition. It is proved that the counting efficiency depends
      strongly on the energy E(LMM). Therefore, it is important to know the optimum
      value for E(LMM) and how to obtain it. To this end, the equations of the
      probabilities and the reduced energies for 3816 atomic rearrangement pathways
      have been derived. To average the equations, a computer program called MOYEN has
      been developed. The energy E(LMM) has been computed for 55Fe and 125I from
      different mean value definitions.

PMID- 16574422
TI  - Decay Data Evaluation Project (DDEP): evaluation of the main 233Pa decay
      characteristics.
AB  - The results of a decay data evaluation are presented for 233Pa (beta-) decay to
      nuclear levels in 233U. These evaluated data have been obtained within the Decay
      Data Evaluation Project using information published up to 2005.

PMID- 16574423
TI  - The influence of uncertainties of measurements in laboratory performance
      evaluation using an intercomparison program of radionuclide assays in
      environmental samples.
AB  - To show the influence of measurement uncertainties in performance evaluation of
      laboratories, data from 42 comparison runs were evaluated using two statistical
      criteria. The normalized standard deviation, D, used by US EPA, that mainly takes
      into account the accuracy, and the normalized deviation, E, that includes the
      individual laboratory uncertainty used for performance evaluation in the key
      comparisons by BIPM. The results show that data evaluated by the different
      criteria give a significant deviation of laboratory performance in each
      radionuclide assay when we analyse a large quantity of data.

PMID- 16574424
TI  - An approach based on the SIR measurement model for determining the ionization
      chamber efficiency curves, and a study of 65Zn and 201Tl photon emission
      intensities.
AB  - The measurement model used to determine ionization chamber efficiency curves
      accounts from the outset for impurity corrections and beta spectrum shapes. The
      curves are represented by exponentials of polynomials whose coefficients are
      adjusted using non-linear least-squares minimization. The curves are validated by
      comparing with SIR key comparison reference values (KCRVs) and other published
      curves. The associated covariance matrix is also evaluated. Deviations from model
      predictions for 65Zn and 201Tl using recommended nuclear data are studied.

PMID- 16574425
TI  - Reduced glucocorticoid receptors: consequence or cause of depression?
AB  - Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is common in
      patients with major depression. A recent study demonstrates that reduced
      expression of the glucocorticoid receptor in mice causes depression-like
      behaviors and HPA axis dysfunction following stressor exposure. This model offers
      a novel system for the study of the pathophysiology that underlies depression
      like behaviors. It also adds to the growing evidence that implicates
      glucocorticoid receptor dysfunction in depression.

PMID- 16574426
TI  - Multi-chaperone complexes regulate the folding of interferon-gamma in the
      endoplasmic reticulum.
AB  - The quality control mechanisms directing the folding of cytokines in the
      endoplasmic reticulum (ER) are poorly understood. We have investigated ER
      chaperone usage by the cytokine interferon-gamma (IFN-gamma). ATP-depletion or
      inhibition of N-glycosylation was found to cause IFN-gamma to accumulate into
      detergent-insoluble aggregates in the ER. Six chaperones, GRP94, GRP78, ERp72,
      PDI, CaBP1/P5 and CRT were found to associate with IFN-gamma during its steady
      state folding. Interaction of the five first chaperones with IFN-gamma was
      regulated co-ordinately by ATP. These chaperones were recently reported to be
      part of a multi-chaperone complex involved in the folding of complex, multi
      subunit proteins. Our data suggest that also proteins with a relatively simple
      quaternary structure such as cytokines may fold in association with this complex.
      In addition, we identified calreticulin as the major chaperone interacting with
      IFN-gamma, and the related class II cytokine interleukin-10, during heat-shock in
      vivo. IFN-gamma was maintained in a folding-competent form by calreticulin during
      heat-shock and released during subsequent recovery at 37 degrees C. This
      interaction was observed in both recombinant (CHO-F11) and natural producer cells
      (Jurkat, NK-92MI) of IFN-gamma. Since cytokines such as IFN-gamma and IL-10 are
      frequently produced in the course of inflammatory conditions associated with
      fever, the thermo-protective effect of calreticulin may constitute a previously
      unrecognized component of the cellular cytokine production machinery, of likely
      relevance in sustaining cytokine folding and secretion in pathophysiological
      conditions.

PMID- 16574427
TI  - Activation of the selenoprotein SEPS1 gene expression by pro-inflammatory
      cytokines in HepG2 cells.
AB  - SEPS1 (also called selenoprotein S, SelS) plays an important role in the
      production of inflammatory cytokines and its expression is activated by
      endoplasmic reticulum (ER) stress. In this report, we have identified two binding
      sites for the nuclear factor kappa B in the human SEPS1 promoter. SEPS1 gene
      expression, protein levels and promoter activity were all increased 2-3-fold by
      TNF-alpha and IL-1beta in HepG2 cells. We have also confirmed that the previously
      proposed ER stress response element GGATTTCTCCCCCGCCACG in the SEPS1 proximate
      promoter is fully functional and responsive to ER stress. However, concurrent
      treatment of HepG2 cells with IL-1beta and ER stress produced no additive effect
      on SEPS1 gene expression. We conclude that SEPS1 is a new target gene of NF
      kappaB. Together with our previous findings that SEPS1 may regulate cytokine
      production in macrophage cells, we propose a regulatory loop between cytokines
      and SEPS1 that plays a key role in control of the inflammatory response.

PMID- 16574428
TI  - Modulation of catecholamine release from rat striatal slices by the fixed
      combination of aspirin, paracetamol and caffeine.
AB  - The fixed combination of aspirin, paracetamol (acetaminophen) and caffeine has
      been used successfully to treat different kinds of pain including migraine
      attacks. Even when this formulation has been marketed for a long time, the exact
      molecular mechanisms underlying its therapeutic effectiveness have not been
      completely elucidated. In the present investigation, we have studied the effects
      of the fixed combination of aspirin, paracetamol and caffeine (APC) on the
      release of dopamine and noradrenaline from rat striatal slices in an attempt to
      find potential new mechanisms of action of this widely used analgesic
      combination. We found that APC produced a significant reduction in extracellular
      dopamine and a dramatic increase in norepinephrine release from the slices
      incubated with different concentrations of APC (dose relationship 1:1:0.2,
      corresponding to the dose-relationship of Thomapyrin). These findings suggest
      that the modulation of catecholaminergic neurotransmission is a new
      pharmacological effect of APC which could explain the mechanism of action of this
      formulation, considering that the independent effect of either compound alone
      does not explain the potent antinociceptive properties when observed in
      combination.

PMID- 16574429
TI  - Adrenoceptor blockade alters plasma gelatinase activity in patients with heart
      failure and MMP-9 promoter activity in a human cell line (ECV304).
AB  - This study assessed the effects of short-term adrenoceptor blockade on plasma
      matrix metalloproteinase (MMP) activity in patients with heart failure, and the
      ability of adrenoceptor stimulation to modulate matrix metalloproteinase-9 (MMP
      9) promoter activity in vitro. Patients with heart failure received standard
      therapy or standard therapy plus carvedilol. Plasma MMP activity was determined
      by zymography and tissue inhibitor (TIMP-1) expression was measured by
      immunoblotting. MMP-9 promoter activity was assessed in transfected ECV304 cells
      following exposure to isoprenaline or phenylephrine in the absence or presence of
      either propranolol or prazosin. In patients with heart failure, carvedilol
      attenuated the increase in proMMP-9 activity observed at 4 and 12 weeks in non
      beta-blocker-treated patients (44.0 +/- 4.9 AU versus 60.8 +/- 6.7 AU; P < 0.05).
      Although TIMP-1 expression was unaltered, the MMP-9:TIMP-1 ratio was lower in
      those receiving carvedilol at 4 and 12 weeks (0.54 +/- 0.07 versus 1.04 +/- 0.17;
      P < 0.05). Isoprenaline transiently increased MMP-9 promoter activity after 4 h
      exposure (80.6 +/- 14.8-fold; P < 0.001) before returning to baseline. The
      response to isoprenaline was prevented by propranolol (P < 0.01). Phenylephrine
      caused a biphasic increase in MMP-9 promoter activity, with the greatest increase
      occurring at 24 h (23 +/- 3.7-fold) compared to baseline. This response was
      unaffected by co-incubation with prazosin. In conclusion, treatment with a mixed
      alpha1/beta-adrenoceptor antagonist attenuates MMP activity and tips the
      degradative balance to a less degradative phenotype in heart failure patients.
      Furthermore, adrenoceptor stimulation increases MMP-9 promoter activity, which is
      inhibited by beta- but not alpha-adrenoceptor blockade. Therefore, mixed
      adrenoceptor blockade may reduce remodeling in heart failure as a direct
      consequence of a beta-adrenoceptor-mediated reduction in MMP-9 transcription.

PMID- 16574430
TI  - Bladder cancer, a two phased disease?
AB  - The processes of intraepithelial migration, intraluminal seeding, and field
      cancerization as models for initiation, spread, and recurrences of urothelial
      cell carcinoma (UCC) are reviewed in light of recent molecular investigations.
      The accumulated molecular data on synchronous and metachronous tumors indicate
      that the majority of recurrent and multiple tumors are monoclonal. Molecular data
      has also shown the presence of chromosomal and genetic changes in precursor
      lesions as well as in normal urothelial cells. Genetic-histological mapping of
      cystectomized bladders has shown that overt tumors occur as local events in areas
      of genetically altered urothelium. A model is put forward in which the tumor
      process is initiated by genetically altered but histologically normal cells that
      produce fields of altered cells by intraepithelial displacement. By the
      accumulation of further genetic changes the fields of altered urothelium reaches
      a state of criticality, which locally may produce frank tumors.

PMID- 16574431
TI  - Temporal regulation of EphA4 in astroglia during murine retinal and optic nerve
      development.
AB  - Eph receptors and their ephrin ligands play important roles in many aspects of
      visual system development. In this study, we characterized the spatial and
      temporal expression pattern of EphA4 in astrocyte precursor cell (APC) and
      astrocyte populations in the murine retina and optic nerve. EphA4 is expressed by
      immotile optic disc astrocyte precursor cells (ODAPS), but EphA4 is downregulated
      as these cells migrate into the retina. Surprisingly, mature astrocytes in the
      adult retina re-express EphA4. Within the optic nerve, EphA4 is expressed in
      specialized astrocytes that form a meshwork at the optic nerve head (ONH). Our in
      vitro and in vivo data indicate that EphA4 is dispensable for retinal ganglion
      cell (RGC) axon growth and projections through the chiasm. While optic stalk
      structure, APC proliferation and migration, retinal vascularization, and
      oligodendrocyte migration appear normal in EphA4 mutants, the expression of EphA4
      in APCs and in the astrocyte meshwork at the ONH has implications for optic nerve
      pathologies.

PMID- 16574432
TI  - Low birth weight is associated with reduced adiponectin concentration in adult.
AB  - PURPOSE: Low birth weight has been associated with metabolic and vascular
      diseases, but the precise mechanism is debated. Adiponectin is one of the key
      molecules in metabolic disease, and a decrease in level precedes the onset of
      type 2 diabetes and development of atherosclerosis. Our aim is to examine whether
      low birth weight is associated with adiponectin concentration in adult. METHODS:
      We conducted a population-based cross-sectional study of 2277 subjects (1661 men
      and 616 women) aged 35 to 66 years who had their self-reported birth weights and
      adiponectin concentrations measured as adults. RESULTS: After adjusting for
      potential confounders, including age, sex, current body mass index (BMI), smoking
      status, alcohol consumption, and exercise, geometric mean adiponectin levels were
      6.63, 6.45, 6.86, 7.05, 6.75, and 7.22 microg/mL for subjects with birth weights
      less than 2500, 2500 to less than 2800, 2800 to less than 3000, 3000 to less than
      3200, 3200 to less than 3500, and greater than 3500 g, respectively. A positive
      association was found between birth weight and adiponectin concentration (trend p
      = 0.002). Stratified by current BMI of 25 kg/m2, a positive association was not
      observed for subjects with a BMI less than 25 kg/m2, but was pronounced in those
      with a BMI of 25 kg/m2 or greater. CONCLUSION: This study indicates that low
      birth weight contributes to decreased adiponectin concentrations in adult life
      independently of current BMI, especially for obese subjects.

PMID- 16574433
TI  - The false fame illusion in people with memories about a previous life.
AB  - The present study examined whether individuals with full-blown memories of highly
      implausible events are prone to commit source monitoring errors. Participants
      reporting previous-life memories and those without such memories completed a
      false fame task. This task provides an index of source monitoring errors (i.e.,
      misclassifying familiar non-famous names as famous names). Participants with
      previous-life memories had a greater tendency to judge the names of previously
      presented non-famous people as famous than control participants. The two groups
      did not differ in terms of correct recognition of new non-famous names and famous
      names. Although dissociation, cognitive failures, sleep-related experiences,
      depressive symptoms, and signs of psychological distress were all significantly
      higher in participants with previous-life memories than in controls, these
      variables did not predict the false fame illusion.

PMID- 16574434
TI  - Voluntary pelvic floor muscle control--an fMRI study.
AB  - Storage and periodic expulsion of urine by the bladder are controlled by central
      pathways and organized as simple on-off switching circuits. Several reports
      concerning aspects of micturition control have identified distinct regions in the
      brainstem, like the pontine micturition center (PMC) and the periaqueductal gray
      (PAG), as well as the cerebellum, basal ganglia, limbic system, and cortical
      areas that are organized in a widespread network. The present study focused on
      the involvement of these specific brain regions in pelvic floor muscle control.
      Functional magnetic resonance imaging (fMRI) was performed at 3T in 11 healthy
      women with urge to void due to a filled bladder, who were instructed to either
      imitate voiding by releasing or to imitate interruption of voiding by contracting
      pelvic floor muscles. None of the subjects was able to start voiding during the
      experiments, presumably due to subconscious restraint resulting from the
      inconvenient situation. Relaxation and contraction of pelvic floor muscles
      induced strong and similar activation patterns including frontal cortex, sensory
      motor cortex, cerebellum, and basal ganglia. Furthermore, well-localized
      activations in the PMC and the PAG were identified. To our knowledge, this is the
      first study using fMRI to demonstrate micturition-related activity in these
      brainstem structures. The presented approach proved to characterize the
      widespread central network in pelvic floor muscle control. Thus, in patients with
      voiding dysfunction, fMRI will be useful to elucidate the individual disturbance
      level.

PMID- 16574435
TI  - Phylogenetic relationships among Syndermata inferred from nuclear and
      mitochondrial gene sequences.
AB  - Phylogenetic relationships among Syndermata have been extensively debated, mainly
      because the sister-group of the Acanthocephala has not yet been clearly
      identified from analyses of morphological and molecular data. Here we conduct
      phylogenetic analyses on samples from the 4 classes of Acanthocephala
      (Archiacanthocephala, Eoacanthocephala, Polyacanthocephala, and
      Palaeacanthocephala) and the 3 Rotifera classes (Bdelloidea, Monogononta, and
      Seisonidea). We do so using small-subunit (SSU) and large-subunit (LSU) ribosomal
      DNA and cytochrome c oxidase subunit 1 (cox 1) sequences. These nuclear and
      mitochondrial DNA sequences were obtained for 27 acanthocephalans, 9 rotifers,
      and representatives of 6 phyla that were used as outgroups. Maximum parsimony
      (MP), maximum likelihood (ML), and Bayesian analyses were conducted on the
      nuclear rDNA(SSU+LSU) and the combined sequence dataset(SSU+LSU+cox 1 genes).
      Phylogenetic analyses of the combined rDNA and cox 1 data uniformly provided
      strong support for a clade including rotifers plus acanthocephalans (Syndermata).
      Strong support was also found for monophyly of Acanthocephala in analyses of the
      combined dataset or rDNA sequences alone. Within the Acanthocephala the
      monophyletic grouping of the representatives of each class was strongly
      supported. Our results depicted Archiacanthocephala as the sister-group to the
      remaining acanthocephalans. Analyses of the combined dataset recovered a sister
      group relationship between Acanthocephala and Bdelloidea by parsimony,
      likelihood, and Bayesian methods. Support for this clade was generally strong.
      Alternative topologies that depicted a different rotifer sister-group of
      Acanthocephala (or monophyly of Rotifera) were significantly worse. In this
      paraphyletic assemblage of rotifers, the relative positions of Seisonidea and
      Monogononta to the clade Bdelloidea+Acanthocephala were inconsistent among trees
      based on different inference methods. These results indicate that Bdelloidea is
      the free-living sister-group to acanthocephalans, which should prove key for
      comparative investigations of the morphological, molecular, and ecological
      changes accompanying the evolution of parasitism.

PMID- 16574436
TI  - Ecological speciation in a Caribbean marine sponge.

PMID- 16574437
TI  - Comment to: Status epilepticus induced by star fruit intoxication in patients
      with chronic renal disease.

PMID- 16574438
TI  - Alterations in erythrocyte membrane protein composition in advanced non-small
      cell lung cancer.
AB  - Cancer can be associated with hematological complications related to red blood
      cell (RBC) function, whose physiological roles have now been expanded since it is
      now known that RBC are also signalling cells. The aim of this study was to
      explore the alterations occurring in the protein composition of RBC in advanced
      non-small cell lung cancer (NSCLC). Blood samples from 21 patients with advanced
      (stages III-IV) NSCLC (16 squamous cell carcinomas and 5 adenocarcinomas), and
      from 21 healthy volunteers were used. Samples from 6 randomly selected patients
      and 6 controls were used for the screening of erythrocyte ghost alterations by
      Differential Scanning Calorimetry (DSC). Samples from 15 patients and 15
      controls, different from those used in the DSC measurements, were randomly
      selected for analysis of the expression of glycophorin (GP) species, band 3, and
      glycoproteins by SDS-PAGE and Western blotting or lectin enzyme immunoassays.
      Additionally, 5 patients with chronic obstructive pulmonary disease (COPD) were
      used as a control group representative of a benign inflammatory disease. Blood
      samples from the COPD patients were used to analyze the expression of GPs, band 3
      and syaloglycoproteins. We observed the following in NSCLC: (a) changes in GP
      expression levels, mainly decreases in the GPA and GPC monomers, and in the GPAB
      dimers; (b) a decrease in the band 3 protein level, and (c) alterations in the
      expression of different sialoglycoproteins. RBC from the COPD patients also
      showed protein abnormalities, some of them, especially at the level of band 3 and
      the syaloglycoproteins, being similar to those in NSCLC.

PMID- 16574439
TI  - ITP.
AB  - I describe how we came to microinject inositol trisphosphate into sea urchin eggs
      and found that is was a very potent activator of calcium release.

PMID- 16574440
TI  - Calcium signals and mitochondria at fertilisation.
AB  - At fertilisation, Ca(2+) signals activate embryonic development by stimulating
      metabolism, exocytosis and endocytosis, cytoskeletal remodelling, meiotic
      resumption and recruitment of maternal RNAs. Mitochondria present in large number
      in eggs have long been thought to act as a relay in Ca(2+) signalling at
      fertilisation. However, only recently have studies on ascidians and mouse proven
      that sperm-triggered Ca(2+) waves are transduced into mitochondrial Ca(2+)
      signals that stimulate mitochondrial respiration. Mitochondrial Ca(2+) uptake can
      substantially buffer cytosolic Ca(2+) concentration and the concerted action of
      heterogeneously distributed mitochondria in the mature egg may modulate the
      spatiotemporal pattern of sperm-triggered Ca(2+) waves. Regulation of
      fertilisation Ca(2+) signals could also be achieved through mitochondrial ATP
      production and mitochondrial oxidant activity but these hypotheses remain to be
      explored. A critically poised dynamic interplay between Ca(2+) signals and
      mitochondrial metabolism is stimulated at fertilisation and may well determine
      whether the embryo can proceed further into development. The monitoring of Ca(2+)
      signals and mitochondrial activity during fertilisation in living zygotes of
      diverse species should confirm the universality of the role for sperm-triggered
      Ca(2+) waves in the activation of mitochondrial activity at fertilisation.

PMID- 16574441
TI  - The molecular players of sperm-egg fusion in mammals.
AB  - Fertilization includes a series of cellular interactions culminating with the
      fusion of gamete membranes, creating a zygote. Two ADAM proteins present on
      sperm, fertilin beta and cyritestin, drew much attention. However, gene deletion
      in mice showed that fusion can happen in their absence. The presence of the
      integrin alpha6beta1 on egg, a putative fertilin beta receptor, is also
      dispensable. In contrast, sperm lacking Izumo, a molecule with a single Ig
      domain, are unable to fuse. On the egg side, a role for GPI-anchored molecules
      has been shown, and in mice lacking both tetraspanins CD9 and CD81 fertilization
      is completely blocked.

PMID- 16574442
TI  - Fracture toughness of bovine claw horn from cattle with and without vertical
      fissures.
AB  - The study was undertaken to determine whether the claw horn from cows suffering
      from vertical fissures (sandcracks) is weaker with regard to fracture formation
      than claw horn from cows without vertical fissures. Fracture toughness was
      determined using a composite testing procedure previously developed for use in
      equine hoof horn. Twenty cows with vertical fissures of the lateral front claw
      were compared with 20 case controls. Due to the calibration technique needed as
      part of the testing method results were obtained for only five animals in each
      group; cows with and without vertical fissures had median J-integrals of
      8182J/m(2) and 8483J/m(2), respectively, but the difference was not statistically
      significant. Although the numbers are small it is suggested that since no
      difference existed in the fracture toughness of the claw horn from the two groups
      of cattle, vertical fissure formation is not directly dependent on the
      biomechanical property of the horn itself.

PMID- 16574443
TI  - Dynamic shim updating on the human brain.
AB  - Dynamic alteration of shim settings during a multi-slice imaging experiment can
      improve static magnetic-field homogeneity over extended volumes. In this report,
      a pre-emphasized dynamic shim updating (DSU) system capable of rapidly updating
      all non-degenerate zeroth through second-order shims is presented and applied to
      high-field multi-slice imaging studies on the human brain. DSU is utilized in
      both non-oblique and oblique slicing geometries while updating in-plane and
      through-slice shims. Image-based magnetic-field maps are used to quantify
      homogeneity improvements and comparisons are made on a slice-specific basis
      between static global shimming and increasing orders of shim inclusion utilized
      DSU. The influence of oblique slicing geometry on DSU-utilized global homogeneity
      is also quantified computationally. Finally, the effect of DSU on susceptibility
      artifact reduction in single-shot axial-sliced EPI is analyzed using experimental
      acquisitions.

PMID- 16574444
TI  - Alanine check points in HNN and HN(C)N spectra.
AB  - Rapid resonance assignment is a key requirement in structural genomics research
      by NMR. In this context we present here two new pulse sequences, namely, HNN-A
      and HN(C)N-A that have been developed by simple modification of the previously
      described pulse sequences, HNN and HN(C)N [S.C. Panchal, N.S. Bhavesh, R.V.
      Hosur, Improved 3D triple resonance experiments, HNN and HN(C)N, for H(N) and 15N
      sequential correlations in (13C, 15N) labeled proteins: application to unfolded
      proteins, J. Biomol. NMR, 20 (2001) 135-147]. These increase the number of
      start/check points in HNN and/or HN(C)N spectra and hence help in pacing up
      resonance assignment in proteins.

PMID- 16574445
TI  - Recoupling of chemical-shift anisotropy powder patterns in MAS NMR.
AB  - A comparison of three different implementations of the chemical-shift recoupling
      experiment of Tycko et al. [R. Tycko, G. Dabbagh, P.A. Mirau, Determination of
      chemical-shift-anisotropy lineshapes in a two-dimensional magic-angle-spinning
      NMR experiment, J. Magn. Reson. 85 (1989) 265-274] is presented. The methods seek
      to reduce the effects of artefacts resulting from pulse imperfections and
      residual C-H dipolar coupling in organic solids. An optimised and constant time
      implementation are shown to give well-defined and artefact free powder pattern
      lineshapes in the indirectly observed dimension for both sp2 and sp3 carbon
      sites. Experimental setup is no more demanding than for the original experiment,
      and can be implemented using standard commercial hardware.

PMID- 16574446
TI  - Molecular dynamics of a biophysical model for beta2-adrenergic and G protein
      coupled receptor activation.
AB  - This study analyzes 16 molecular dynamic simulations of a biophysical model for
      beta(2)-adrenergic (B2AR) and G protein-coupled receptor (GPCR) activation. In
      this model, a highly conserved cysteine residue, C106 (C3.25 or CysIII:01),
      provides a free sulfhydryl or thiol group in an acid-base equilibrium between
      uncharged (RSH) and charged (RS(-)) states that functions as an electrostatic
      molecular switch for receptor activation. The transition of C106 in the B2AR
      between acid and base states significantly changes the helical/transmembrane (TM)
      domain interactions and the electrostatic interaction energy differences
      (DeltaDeltaE(EL)). The DeltaDeltaE(EL) changes correlate well with the
      experimentally observed ligand efficacies. The TM interaction energies display
      patterns compatible with those previously recognized as responsible for GPCR
      activation. Key differences between the agonist, epinephrine, and the antagonist,
      pindolol, are seen for the TM3 x 6, TM3 x 4, TM6 x 7 and TM1 x 7 interaction
      energies. Pindolol also produces a weaker DeltaDeltaE(EL) interaction and less TM
      interaction energy changes, which are important differences between the agonist
      and antagonist ligands. The D115E mutant with pindolol displays a greater
      DeltaDeltaE(EL) and TM interactions than for the wild-type B2AR with pindolol.
      This explains the higher activity of pindolol in the D115E mutant. The
      constitutively active D130A mutant displays TM interaction patterns similar to
      those for the activating ligands implying a common pattern for receptor
      activation. These findings support the broad concept of protean agonism and
      demonstrate the potential for allosteric modulation. They also demonstrate that
      this two-state model agrees with many previous experimental and theoretical
      observations of GPCRs.

PMID- 16574447
TI  - Computation of through-space NMR shielding effects by small-ring aromatic and
      antiaromatic hydrocarbons.
AB  - The GIAO-HF method in Gaussian 03 was employed to calculate the isotropic NMR
      shielding values of a diatomic hydrogen probe above simple small-ring aromatic
      and antiaromatic hydrocarbons, including neutral and ionic examples. Subtraction
      of the isotropic shielding of diatomic hydrogen by itself allowed the prediction
      of through-space proton NMR shielding increment surfaces for these systems.
      Substantial shielding was observed above the center of aromatic rings, regardless
      of whether the ring was pi-aromatic or sigma-aromatic, and also regardless of the
      charge. In sharp contrast, deshielding was observed above the center of
      antiaromatic rings, regardless of whether the ring was pi-aromatic or sigma
      aromatic, and also regardless of the charge. Shielding increment values at 2.5
      angstrom above the ring centers were compared to NICS values at the same
      position. The shielding effects predicted by using diatomic hydrogen as a
      computational probe are diagnostic of whether a structure possesses aromaticity
      or antiaromaticity.

PMID- 16574448
TI  - Bayesian-regularized genetic neural networks applied to the modeling of non
      peptide antagonists for the human luteinizing hormone-releasing hormone receptor.
AB  - Bayesian-regularized genetic neural networks (BRGNNs) were used to model the
      binding affinity (IC(50)) for 128 non-peptide antagonists for the human
      luteinizing hormone-releasing hormone (LHRH) receptor using 2D spatial
      autocorrelation vectors. As a preliminary step, a linear dependence was
      established by multiple linear regression (MLR) approach, selecting the relevant
      descriptors by genetic algorithm (GA) feature selection. The linear model showed
      to fit the training set (N=102) with R(2)=0.746, meanwhile BRGNN exhibited a
      higher value of R(2)=0.871. Beyond the improvement of training set fitting, the
      BRGNN model overcame the linear one by being able to describe 85% of test set
      (N=26) variance in comparison with 73% the MLR model. Our non-linear QSAR model
      illustrates the importance of an adequate distribution of atomic properties
      represented in topological frames and reveals the electronegativities, masses and
      polarizabilities as the most influencing atomic properties in the structures of
      the heterocycles under analysis for having an appropriate LHRH antagonistic
      activity. Furthermore, the ability of the non-linear selected variables for
      differentiating the data was evidenced when total data set was well distributed
      in a Kohonen self-organizing map (SOM).

PMID- 16574449
TI  - Cardiac output and muscle blood flow during rest-associated apneas of elephant
      seals.
AB  - In order to evaluate hemodynamics and blood flow during rest-associated apnea in
      young elephant seals (Mirounga angustirostris), cardiac outputs (CO,
      thermodilution), heart rates (HR), and muscle blood flow (MBF, laser Doppler
      flowmetry) were measured. Mean apneic COs and HRs of three seals were 46% and 39%
      less than eupneic values, respectively (2.1+/-0.3 vs. 4.0+/-0.1 mL kg(-1) s(-1),
      and 54+/-6 vs. 89+/-14 beats min(-1)). The mean apneic stroke volume (SV) was not
      significantly different from the eupneic value (2.3+/-0.2 vs. 2.7+/-0.5 mL kg(
      1)). Mean apneic MBF of three seals was 51% of the eupneic value. The decline in
      MBF during apnea was gradual, and variable in both rate and magnitude. In
      contrast to values previously documented in seals during forced submersions (FS),
      CO and SV during rest-associated apneas were maintained at levels characteristic
      of previously published values in similarly-sized terrestrial mammals at rest.
      Apneic COs of such magnitude and incomplete muscle ischemia during the apnea
      suggest that (1) most organs are not ischemic during rest-associated apneas, (2)
      the blood O(2) depletion rate is greater during rest-associated apneas than
      during FS, and (3) the blood O(2) store is not completely isolated from muscle
      during rest-associated apneas.

PMID- 16574450
TI  - Does bradycardia or hypertension enhance gas transfer in rainbow trout
      (Oncorhynchus mykiss)?
AB  - Experiments were conducted to test the hypothesis that branchial gas transfer is
      enhanced in rainbow trout during hypoxia or hypercarbia by bradycardia and
      systemic vasoconstriction. Gas transfer was indirectly assessed by continuous
      monitoring of arterial blood gases, PaO2 and PaCO2. Cardiac frequency was
      maximally decreased by 34.9+/-4.3 and 8.6+/-3.2 bpm in hypoxic and hypercarbic
      fish, respectively. Pre-treating fish with atropine (1micromol kg(-1)) attenuated
      or abolished the bradycardia during hypoxia and hypercarbia, respectively.
      However, there were no significant differences in the arterial blood gases
      between the control and atropinized fish. Dorsal aortic blood pressure was
      increased maximally by 11.3+/-2.8 and 17.7+/-2.0mm Hg in the hypoxic and
      hypercarbic fish. Pre-treatment of fish with prazosin (2.4micromol kg(-1))
      prevented these increases in blood pressure. Blood gases were unaltered by
      prazosin treatment in the hypercarbic fish. However, in the hypoxic fish, gas
      transfer appeared to be impaired by prazosin on the basis of lowered PaO2 (by
      approximately 35 mm Hg compared to control fish) and increased PaCO2 (by
      approximately 0.3mm Hg). Because the normal hyperventilatory response to hypoxia
      was prevented by prazosin, it is possible that the impairment of gas transfer was
      related to inadequate ventilation rather than to any differences in the pressor
      response. The present results provide no evidence that gas transfer in rainbow
      trout is enhanced by bradycardia nor do they reveal any obvious benefit
      associated with the increases in blood pressure that accompany hypoxia and
      hypercarbia.

PMID- 16574451
TI  - Effect of cobalt ions on lipid and sterol metabolism in the marine invertebrates
      Mytilus galloprovincialis and Actinia equina.
AB  - The lipid and sterol fractions of the mussel Mytilus galloprovincialis and the
      anemone Actinia equina were analyzed before and after incubation with cobalt
      ions. There were significant changes in the lipid and sterol composition,
      strongly depending on the cobalt ions concentrations. The changes in the lipid
      composition of both invertebrates were different for neutral lipids and
      phospholipids. These changes concern the length of the fatty acid chains as well
      as their unsaturation. The cobalt ions inhibited the oxidation of sterols and
      their alkylation at C-24. Because of these results we can assume that some of the
      changes caused by cobalt ions might possess adaptive value.

PMID- 16574452
TI  - Cloning and characterization of the executioner caspases 3, 6, 7 and Hsp70 in
      hyperthermic Atlantic salmon (Salmo salar) embryos.
AB  - Hyperthermia during embryogenesis has been reported to induce deformities in
      Atlantic salmon (Salmo salar). To examine the involvement of executioner caspases
      in hyperthermia-induced cell-death in a poikilotherm vertebrate species, five
      genes encoding caspase-3,-6, and -7 were cloned from Atlantic salmon, and the
      expression was studied in thermal stressed salmon embryos. The salmon genome
      contained two genetically distinct variants of both salmon caspase-3 and caspase
      6 that is likely the result of two independent chromosome or genome duplications.
      Whereas only partial caspase-3A encoding sequences were isolated, the full-length
      caspase-3B cDNA encodes the inactive proenzyme of 279 amino acids (aa) consisting
      of an N-terminal prodomain and the large and the small subunit. The salmon
      caspase-6A and caspase-6B proenzymes include an additional linker region between
      the two subunits. The deduced salmon caspase-7 consists of only 245 aa and lacks
      the prodomain and part of the large subunit similar to the predicted caspase-7 of
      the puffer fish Tetraodon sp.. Increased apoptotic activity as evidenced by
      cleavage of nuclear DNA was demonstrated in salmon embryos incubated at 18-20
      degrees C for 84 h after acclimatization at 8 degrees C. Hyperthermia-induced
      activation of the executioner caspases was indicated by the increased mRNA levels
      of caspase-3B, caspase-6A/B and caspase-7 after 54 h heat exposure as quantified
      by real-time RT-PCR. The 2-2.5 fold increase in the mRNA expression of the heat
      shock protein Hsp70 gene coincided with the peak mRNA values of the executioner
      caspases. Whole-mount in situ hybridization of the salmon embryo identified
      caspase-7 mRNA in the lens exclusively, while caspase-3B and caspase-6A/B were
      expressed in multiple tissues of exposed and control embryos. Interestingly,
      cardiac expression of caspase-6A/B was only identified in heat stressed embryos.
      Altogether, these results shed light on evolutionary aspects of the executioner
      caspases in vertebrates and their expression in salmon embryos exposed to
      hyperthermia. In particular, the heat sensitive caspase-6 expression in the
      embryonic heart is of interest since cardiac malformations are an emergent
      problem in salmon aquaculture.

PMID- 16574453
TI  - Clinical and mutational investigations of tyrosinemia type II in Northern
      Tunisia: identification and structural characterization of two novel TAT
      mutations.
AB  - Tyrosinemia type II or Richner-Hanhart Syndrome (RHS) is an autosomal recessive
      disorder characterized by keratitis, palmoplantar keratosis, mental retardation,
      and elevated blood tyrosine levels. The disease is due to a deficiency of hepatic
      cytosolic tyrosine aminotransferase (TATc), an enzyme involved in the tyrosine
      catabolic pathway. Because of the high rate of consanguinity this disorder seems
      to be relatively common among the Arab and Mediterranean populations. RHS is
      characterized by inter and intrafamilial phenotypic variability. A large spectrum
      of mutations within TATc gene has been shown to be responsible for RHS. In the
      present study, we report the clinical features and the molecular investigation of
      RHS in three unrelated consanguineous Tunisian families including 7 patients with
      confirmed biochemical diagnosis of tyrosinemia type II. Mutation analyses were
      performed and two novel missense mutations were identified (C151Y) and (L273P)
      within exon 5 and exon 8, respectively. The 3D-structural characterization of
      these mutations provides evidence of defective folding of the mutant proteins,
      and likely alteration of the enzymatic activity. Phenotype variability was
      observed even among individuals sharing the same pathogenic mutation.

PMID- 16574454
TI  - Subacute combined degeneration of the spinal cord in cblC disorder despite
      treatment with B12.
AB  - Subacute combined degeneration (SCD) of the spinal cord is a characteristic
      complication of vitamin B12 deficiency, but it has never been neuropathologically
      demonstrated in a B12-inborn error of metabolism. In this report SCD is
      documented in a 15-year-old boy with early-onset cobalamin C (cblC) disorder. The
      neuropathologic findings included multifocal demyelination and vacuolation with
      predilection for the dorsal and lateral columns at the mid-thoracic level of the
      spinal cord, confirming the similarity of SCD in cblC disorder to the classic
      adult SCD due to vitamin B12 deficiency. SCD developed in this boy despite
      treatment for cblC disorder that began at 3 months of age. There is clinical and
      experimental evidence to suggest that a deficiency in remethylation with
      concomitant reduction in brain methionine may be the cause of SCD. In this
      patient plasma methionine levels were low without betaine and/or l-methionine
      supplementation and in the normal range for only a 2-year period during
      compliance with therapy. In cblC disorder, a consistent increase in blood
      methionine to high normal or above normal levels by the use of betaine and l
      methionine supplementation may be helpful in preventing SCD. This is especially
      important now that the presymptomatic detection of cblC disorder is possible
      through the expansion of newborn screening.

PMID- 16574455
TI  - Hyponatraemia associated with lopinavir--ritonavir?

PMID- 16574456
TI  - Alloimmunity to RhD in humans.
AB  - The RhD protein is expressed only on human red blood cells (RBC), and is one of
      the most immunogenic of the blood groups. It is of clinical importance since the
      alloantibody (anti-D) can hemolyse D positive RBC after blood transfusion, or
      cause hemolytic disease of the newborn. The immunogenicity of D is better
      understood with the knowledge of the genetic basis of the protein(s) involved,
      the molecular orientation in the RBC membrane, and the nature of the cellular
      immune response to proteins. The adaptive humoral response consists of antigen
      presenting cells, T-cells and B-cells, which interact cooperatively to result in
      antibody against the antigen in question. The anti-D that B-cells produce is
      targeted against surface membrane determinants (B-cell epitopes) and are
      conformational i.e. non-contiguous amino acids. The antigen specific T-cells
      recognize short linear peptides in the context of MHC class II, and these T-cell
      epitopes can reside anywhere in the protein. Since the RhD protein in D-positive
      individuals differs by some 35 amino acids from the RhCcEe protein in D-negative
      individuals, the opportunity for generating immunogenic T-cell epitopes is much
      greater than that for alleles characterized by a single amino acid difference
      e.g. E and e. Multiple conformational B-cell epitopes are also created by the
      presence of several D-specific amino acids in extracellular loops on the red
      cells surface, which may stimulate several B-cell clones and develop a strong
      polyclonal antibody response. With greater understanding comes the possibility of
      manipulating the immune response to D in clinical situations.

PMID- 16574457
TI  - From yeast ammonium transporters to Rhesus proteins, isolation and functional
      characterization.
AB  - Saccharomyces cerevisiae possesses three ammonium transporters from the Mep/Amt
      family involved in ammonium acquisition and retention. We have shown that Rh
      proteins are structurally related to Mep/Amt proteins and that human RhAG and
      RhCG perform bi-directional ammonium transport upon heterologous expression in
      yeast. Using yeast as an expression tool, we have started a structure-function
      analysis of distinct members from the Mep/Amt/Rh super-family.

PMID- 16574458
TI  - Role of RhAG and AQP1 in NH3 and CO2 gas transport in red cell ghosts: a stopped
      flow analysis.
AB  - To clarify the potential role Rh/RhAG and AQP1 proteins in erythrocyte gas
      transport, NH3 and CO2 transport was measured in erythrocyte ghost membrane
      vesicles from rare human variants (Rh(null), CO(null),) and knockout mice
      (homozygous AQP1-/-, Rh-/- and Rhag-/-) exhibiting well-characterized protein
      defects. Transport was measured from intracellular pH (pHi) changes in a stopped
      flow fluorimeter. NH3 transport was measured in chloride-free conditions with
      ghosts exposed to 20 mM inwardly directed gradients of gluconate salts of
      ammonium, hydrazine and methylammonium at 15 degrees C. Alkalinization rates of
      control samples were 6.5+/-0.3, 4.03+/-0.17, 0.95+/-0.08 s(-1) for each solute,
      respectively, but were significantly reduced for Rh(null) and CO(null) samples
      that are deficient in RhAG and AQP1 proteins, respectively. Alkalinization rates
      of Rh(null) ghosts were about 60%, 83% and 94% lower than that in control ghosts,
      respectively, for each solute. In CO(null) ghosts, the lack of AQP1 resulted in
      about 30% reduction of the alkalinization rates as compared to controls, but the
      transport selectivity of RhAG for the three solutes was preserved. Similar
      observations were made with ghosts from KO mice Rhag-/- and AQP1-/-. These
      results confirm the major contribution of RhAG/Rhag in the NH3 conductance of
      erythrocytes and suggest that the reduction of transport rates in the absence of
      AQP1 would be better explained by a direct or indirect effect on RhAG/Rhag
      mediated transport. When ghosts were preloaded with carbonic anhydrase and
      exposed to a 25 mM CO2/HCO3- gradient at 6 degrees C, an extremely rapid kinetics
      of acidification corresponding to CO2 influx was observed. The rate constants
      were not significantly different between controls and human variants (125+/-6 s(
      1)), or between wild-type and KO mice, suggesting no major role of RhAG or AQP1
      in CO2 transport, at least in our experimental conditions.

PMID- 16574459
TI  - Genetics of Paget's disease of bone.
AB  - Paget's disease of bone is a chronic bone disease that affects up to 3% of
      Caucasians older than 55 years. The cause of Paget's disease is unknown but
      involves genetic factors. Familial cases display an autosomal dominant pattern of
      inheritance with incomplete penetrance. Genetic heterogeneity has been
      demonstrated and eight potential susceptibility loci identified. There is sound
      evidence incriminating Sequestosome 1 (SQSTM1) on the long arm of chromosome 5
      (5q35-qter), of which nine mutations have been described in Paget's disease of
      bone. These mutations are located in exons 7 and 8, which encode a highly
      conserved ubiquitin-binding domain. The prevalence of SQSTM1 mutations is about
      10% in France. Tests for SQSTM1 mutations should be done in patients with Paget's
      disease of bone, even where the family history is negative. Detection of a
      mutation allows evaluation of family members to ensure early diagnosis of the
      disease before complications develop.

PMID- 16574460
TI  - [Endometriosis coaching].
AB  - Coaching is a well-known terminology and an approach currently used, particularly
      in the worlds of company management and sport, but its use in the medical field
      appeared only recently. In the latter field, coaching bears behavioral and
      psychological aspects. It can not only be intended to a medical team, but also
      the practionner himself, for a better management of any disease, his patient for
      a better treatment effect and compliance and an optimal coping with the disease.
      In the case of endometriosis, a chronic disease, two key aspects are briefly
      reviewed to illustrate the benefits of coaching and to sensitize health providers
      to this approach. Thus, an appropriate diagnostic strategy should allow to reduce
      the delay in the diagnosis, so frequently blamed, and to identify other
      associated painful diseases. Also, management should be improved as well, not
      only by applying appropriate therapeutic recommandations, and alternative
      measures, but also by a better multidisciplinary support towards patient
      expectations with long-term guidance.

PMID- 16574461
TI  - [Ideas to make the TVT progress].
AB  - Because of the bladder injuries risk and subsequent increase of the intervention
      time due to the bladder integrity checking, many surgeons have abandoned TVT.
      Based on a demonstrative clinical case, we report a simple, fast and effective
      method meant to minimize the risk of bladder injuries and to wonder about the
      mandatory bladder checking by cystoscopy during the TVT sling installation. An
      infiltration of 1% Xylocaine half diluted is carried out in the area laterally to
      the urethra and the bladder, through vaginal and pubic ways. A 360 ml blue of
      methylene solution bladder filling may show quickly and safely a bladder injuries
      occurrence, either a true transfixion or an under mucous route. Using this
      procedure, TVT technique could be no more dangerous or longer than the TOT
      technique.

PMID- 16574462
TI  - [Minimal ovarian stimulation: certainly less dangerous and probably as
      efficient].

PMID- 16574463
TI  - [Mode of delivery of HIV-infected women: a retrospective study of 358 pregnancies
      followed in the same hospital between 2000 and 2004].
AB  - OBJECTIVE: Evaluate the mode of delivery of HIV-infected women and the risk of
      mother-to-child transmission. PATIENTS AND METHODS: A retrospective study
      conducted on HIV-infected women who delivered at the maternity ward of Bichat
      Hospital in Paris between 1st January 2000 and 31(st) December 2004. Pregnancy
      care, antiretroviral therapy, decision of the mode of delivery and neonate
      treatment were conformable to the French recommendations. RESULTS: The analysis
      was performed on 332 cases out of 358 pregnancies followed during this period.
      75% received a Highly Active Anti Retroviral Therapy (HAART), 24% an AZT
      monotherapy and 1% did not receive any antiretroviral treatment. Plasmatic HIV
      viral load was under the level of detectability (50 copies/ml) for 64,6% of women
      under HAART and 28,7% of women under AZT monotherapy. Only 31,7% of women under
      HAART delivered vaginally. 44,7% of women under HAART with undetectable viral
      load at the moment of delivery delivered vaginally. 59,5% of women who were
      allowed to deliver vaginally had finally a vaginal delivery. 332 women gave birth
      to 341 babies with 9 twin pregnancies and one still-birth at 22 WA. Out of these
      340 babies, 3 babies whose mother received HAART were HIV infected (2 in utero
      and 1 per-partum). DISCUSSION AND CONCLUSION: The reasons why only one third of
      HIV-infected women could deliver vaginally in this study are primarily the
      persistence of a detectable HIV viral load under HAART. Women's choice of the
      mode of delivery comes next, which depends on the quality of the counselling
      about the benefits and risks of the cesarean section in the context of HIV
      infection. The third reason is obstetrical contra indications to vaginal delivery
      in the context of HIV infection. In the future, it is possible to reduce the
      incidence of cesarean section in HIV-infected women by elevating the level of HIV
      plasmatic viral load which allowed vaginal delivery (1000 copies/ml), by
      improving the observance to antiretroviral treatment, by adaptating
      antiretroviral medications posology using determination of serum protease
      inhibitors concentration and by modifying obstetrical management with less
      restrictive contra indications to vaginal delivery. However the impact of
      prophylactic cesarean section when plasmatic HIV viral load is undetectable must
      still be evaluated.

PMID- 16574464
TI  - Balancing the 'bio' with the psychosocial in whiplash associated disorders.

PMID- 16574465
TI  - Towards pointwise motion tracking in echocardiographic image sequences--comparing
      the reliability of different features for speckle tracking.
AB  - In this paper, we studied the problem of feature-based motion tracking in
      echocardiographic image sequences. We described the relation between possible
      feature variations and different kinds of tissue motion using a linear
      convolution model. We also showed that motion-feature decorrelation (which means
      that the motion parameters estimated using feature tracking fail to represent the
      underlying tissue motion) compensation is an ill-posed inverse problem. Instead
      of finding a method that may provide better compensation results than previous
      approaches, we used an quantitative measure to compare the reliability of
      tracking features. Experiment results showed that the use of the reliability
      measure improved the robustness of displacement estimation. With the help of the
      reliability measure, we compared the performance of different features using
      simulations and phantom examples. While we noticed that the radio frequency (RF)
      signal outperforms the B-mode (BM) signal in the analysis of small deformation
      (e.g., less than 0.1% compression), we also found out that the BM signal works
      better than the RF signal in the analysis of large deformation (e.g., larger than
      2% compression). The use of a band-passed filtered feature does not result in
      significant improvement in tracking.

PMID- 16574466
TI  - DNA staining with the fluorochromes EtBr, DAPI and YOYO-1 in the comet assay with
      tobacco plants after treatment with ethyl methanesulphonate, hyperthermia and
      DNase-I.
AB  - We applied the alkaline version of the single-cell gel electrophoresis (comet)
      assay to roots and leaves of tobacco (Nicotiana tabacum var. xanthi) seedlings or
      isolated leaf nuclei treated with: (1) the alkylating agent ethyl
      methanesulphonate, (2) necrotic heat treatments at 50 degrees C, and (3) DNase-I.
      All three treatments induced a dose-dependent increase in DNA migration,
      expressed as percentage of tail DNA. A comparison of the fluorochrome DNA dyes
      ethidium bromide, DAPI and YOYO-1 demonstrated that for the alkaline version of
      the comet assay in plants, the commonly used fluorescent dye ethidium bromide can
      be used with the same efficiency as DAPI or YOYO-1.

PMID- 16574467
TI  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces genetic changes in
      murine intestinal tumours and cells with ApcMin mutation.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the mutagenic
      heterocyclic amines derived from cooked meat. In previous animal studies,
      spontaneous tumour formation in B6(Min/+) mice was associated with somatic loss
      of the wild-type Apc+ allele by loss of the entire chromosome 18 or by
      recombination. The objective of this study was to examine genetic changes caused
      by PhIP-exposure in a mouse intestinal cell line and in tumours from hybrid mice
      by keeping track of the chromosomes carrying the two Apc alleles. We transformed
      the SV40 T-immortalised intestinal epithelial cell line IMCE, derived from the
      B6(Min/+) mice by exposure to N-OH-PhIP, and studied the effect on Apc status and
      chromosome 18. Eighteen transformed cultures were obtained and all of them had
      retained the Apc+ allele. Five of seven transformed cultures were tumorigenic
      after implantation in nude mice. Chromosomal analysis of these five cultures and
      the parent IMCE cell line showed that the IMCE cells were near-tetraploid with an
      average of 77 chromosomes/cell, while the tumorigenic cell cultures were all
      triploid to hyper-triploid with a range of 61-69 chromosomes/cell. The number of
      copies of chromosome 18 was about four in the IMCE line and this copy number was
      retained in the transformed lines derived from IMCE. Changes in chromosome 18 and
      Apc during tumour development in vivo were examined in spontaneously formed and
      PhIP-induced intestinal tumours from two hybrid mice strains, i.e. B6(Min/+) - a
      murine FAP model - crossed with either AKR/J or A/J. We evaluated the allelic
      status of Apc, and the heterogenic microsatellite markers D18Mit19 and D18Mit4,
      located at the upper and lower ends of chromosome 18, respectively. In tumours
      from untreated animals, instability in the D18Mit19 and Apc was observed. Upon
      PhIP exposure, the B6(Min/A+) hybrid mouse tumours differed distinctly in genetic
      profile from those obtained from untreated animals and we detected three
      genetically different tumour groups, all of which had apparently retained Apc+.
      One group had allelic balance between the Apc(Min) and Apc+, the second had
      allelic imbalance between the Apc and D18Mit4 alleles, indicative of chromosomal
      stability in the first group and instability in the lower end of chromosome 18 in
      the second group, respectively. The third group showed variable allelic status of
      the three markers. A similar change in genetic profile was also seen in
      intestinal tumours of PhIP-exposed B6(Min/AKR+) hybrid mice, but it was less
      pronounced. Chromosomal breaks and/or recombinational events could be alternative
      explanations for the observed allelic imbalances in chromosome 18 markers in
      intestinal tumours from PhIP-exposed mice.

PMID- 16574468
TI  - Arsenic in the aetiology of cancer.
AB  - Arsenic, one of the most significant hazards in the environment affecting
      millions of people around the world, is associated with several diseases
      including cancers of skin, lung, urinary bladder, kidney and liver. Groundwater
      contamination by arsenic is the main route of exposure. Inhalation of airborne
      arsenic or arsenic-contaminated dust is a common health problem in many ore
      mines. This review deals with the questions raised in the epidemiological studies
      such as the dose-response relationship, putative confounders and synergistic
      effects, and methods evaluating arsenic exposure. Furthermore, it describes the
      metabolic pathways of arsenic, and its biological modes of action. The role of
      arsenic in the development of cancer is elucidated in the context of combined
      epidemiological and biological studies. However, further analyses by means of
      molecular epidemiology are needed to improve the understanding of cancer
      aetiology induced by arsenic.

PMID- 16574469
TI  - Spectral and thermal studies of some chromium and molybdenum complexes with ONO
      donor Schiff bases.
AB  - Reactions of M(CO)(6), where M=Cr and Mo with Schiff bases prepared by the
      condensation of ethanolamine with either acetylacetone or benzoylacetone were
      investigated. The reactions of Cr(CO)(6) in benzene resulted in the formation of
      the tricarbonyl drivatives [Cr(CO)(3)(HL)], HL=acaceaH or baceaH. The HL proved
      to act as a tridentate ligand. The corresponding reactions with Mo(CO)(6) in
      dioxane gave the oxo complexes [Mo(2)O(6)(HL)(2)] with HL was a bidentate. All
      prepared complexes were investigated using elemental analysis, IR, mass
      spectrometry, UV-vis absorption spectra and magnetic measurement. Thermal
      behaviors of the complexes were studied using by thermogravimetry (TG). Schemes
      for the thermal decomposition were proposed along with their mass fragmentation
      patterns.

PMID- 16574470
TI  - FT-Raman and FT-IR spectra, ab initio and density functional studies of 3,4
      dichlorobenzyl alcohol.
AB  - The Fourier transform Raman and Fourier transform infrared spectra of 3,4
      dichlorobenzyl alcohol were recorded in the solid phase. The equilibrium
      geometry, harmonic vibrational frequencies, infrared intensities and Raman
      scattering activities, depolarization ratios, reduced masses were calculated by
      HF and density functional B3LYP method with the 6-311 G** basis set. The scaled
      theoretical wavenumbers showed very good agreement with the experimental values.
      The thermodynamic functions of the title compound were also performed at HF/6
      311G** and B3LYP/6-311G** levels of theory. A detailed interpretations of the
      infrared and Raman spectra of 3,4-dichlorobenzyl alcohol is reported. The
      theoretical spectrograms for FT-IR spectra of the title molecule have been
      constructed.

PMID- 16574471
TI  - Multinuclear NMR spectroscopic and theoretical study on the interactions between
      diperoxovanadate complex and picoline-like ligands.
AB  - To understand the substituting effects of organic ligands on the reaction
      equilibrium, the interactions between diperoxovanadate complex
      [OV(O(2))(2)(H(2)O)](-) and a series of picoline-like ligands in solution were
      explored using 1D multinuclear ((1)H, (13)C, and (51)V) magnetic resonance, 2D
      diffusion ordered spectroscopy (DOSY), and variable temperature NMR in 0.15 mol/l
      NaCl ionic medium for mimicking the physiological conditions. The order of
      reactive capability of the picoline-like ligands with [OV(O(2))(2)(H(2)O)](-) is
      found to be picolinamide>N-methylpicolinamide>methyl picolinate>ethyl picolinate
      approximately propyl picoliniate>isopropyl picolinate. The substituting group
      influences the reactivity by either steric effect or electron-donating effect.
      Competitive coordination interactions result in a series of new seven-coordinated
      peroxovanadate species [OV(O(2))(2)L](-) (L=picoline-like ligands). Their
      coordination ways were confirmed by density functional calculations.

PMID- 16574472
TI  - Influence of bond lengths between substituents and mother molecule on spectral
      properties of pyrazoloquinolines.
AB  - Absorption and luminescent spectra of several new synthesized pyrazolo-quinoline
      possessing different substituents are studied. Absorption spectra of all the
      considered compounds possess five relatively strong absorption bands at about
      430, 320, 270, 253 and about 230 nm. A correlation between the bond lengths
      between the substituent molecule and mother molecule with the observed spectral
      shifts was found. Theoretical spectra obtained within semi-empirical quantum
      chemical AM1 calculation methods seem to be more widened compared to the
      experimental ones due to electron-vibration interactions. However generally a
      good coincidence between spectral positions between experimental and calculated
      spectral peak positions was achieved. The corresponding experimental spectra have
      an absorption edges situated at about 430 nm which appears in fairly good
      agreement with quantum chemical simulations, namely for absorption spectra
      calculated by semi-empirical AM1-method. The red shifts in the experimental
      luminescence spectra are a consequence of electron-vibration interactions which
      increase with the effective radius and polarizabilities of the particular
      substituents.

PMID- 16574473
TI  - FT-IR, FT-Raman spectra and scaled quantum mechanical study of 2,3-dihydroxy
      pyridine and 2,4-dihyroxy-3-nitropyridine.
AB  - The vibrational spectra of 2,3-dihydroxy pyridine (DHP) and 2,4-dihyroxy-3
      nitropyridine (DHNP) have been computed using B3LYP methodology and 6-31G** basis
      set. The solid phase FTIR and FT Raman spectra were recorded in the region 4000
      400 and 3500-100 cm(-1), respectively. A close agreement was achieved between the
      observed and calculated frequencies by refinement of the scale factors.

PMID- 16574474
TI  - Synthesis, characterization and biological activity of bis(phenylimine) Schiff
      base ligands and their metal complexes.
AB  - Metal complexes derived from 2,6-pyridinedicarboxaldehydebis(p
      hydroxyphenylimine); L1, 2,6-pyridinedicarboxaldehydebis (o-hydroxyphenylimine);
      L2, are reported and characterized based on elemental analyses, IR, solid
      reflectance, magnetic moment, molar conductance and thermal analysis (TGA). The
      complexes are found to have the formulae [MX2(L1 or L2)] x nH2O, where M=Fe(II),
      Co(II), Ni(II), Cu(II) and Zn(II), X=Cl in case of Fe(II), Co(II), Ni(II), Cu(II)
      complexes and Br in case of Zn(II) complexes and n=0-2.5. The molar conductance
      data reveal that the chelates are non-electrolytes. IR spectra show that the
      Schiff bases are coordinated to the metal ions in a terdentate manner with NNN
      donor sites of the pyridine-N and two azomethine-N. From the magnetic and solid
      reflectance spectra, it is found that the geometrical structure of these
      complexes are trigonal bipyramidal (in case of Co(II), Ni(II), Cu(II) and Zn(II)
      complexes) and octahedral (in case of Fe(II) complexes). 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
      coordinated water, anions and ligands (L1 and L2) in the subsequent steps. The
      activation thermodynamic parameters, such as, E*, DeltaH*, DeltaS* and DeltaG*
      are calculated from the TG curves using Coats-Redfern method. The synthesized
      ligands, in comparison to their metal complexes also were screened for their
      antibacterial activity against bacterial species, Escherichia coli, Pseudomonas
      aeruginosa, Staphylococcus aureus and Fungi (Candida). The activity data show
      that the metal complexes to be more potent/antibacterial than the parent organic
      ligands against one or more bacterial species.

PMID- 16574475
TI  - Detection of HBV DNA by nested-PCR in a HBsAg and anti-HBc negative blood bank
      donor.
AB  - BACKGROUND: The criteria and protocol adopted in serological screening of blood
      bank donors have significantly reduced the possibility of HBV transmission.
      However, it is possible that, in a very recent phase of HBV infection, HBsAg
      seronegative donors be able to transmit the virus. This study reports a case of a
      donor with this serological profile who was involved in the viral transmission to
      a seronegative receptor. CASE REPORT: A blood donor had her sample tested for
      HBsAg and anti-HBc, which resulted negative. At the second donation the sample
      demonstrated to be seropositive for anti-HBc, anti-HBs and seronegative for
      HBsAg. The first stored sample was tested for the presence of HBV DNA. Two
      fragments could be identified in the genomic region corresponding to HBV core and
      precore. Only one individual was involved in the transfusion of hemo-derivatives
      originating from the processing of this bag, and was seropositive for HBsAg,
      HBeAg and anti-HBc markers and seronegative for the anti-HBe and anti-HBs
      markers. CONCLUSION: This case illustrates the possibility of the occurrence of
      HBV transmission from blood bank donors seronegative for HBsAg and anti-HBc. This
      fact could be associated with the possibility of the donor to be in the pre
      seroconversion phase of a recent infection, when the levels of HBsAg present in
      the circulation are below the limits of detection. The implementation of
      molecular tests or higher sensitivity HBsAg assays could further reduce the risk
      of HBV transmission via blood transfusion.

PMID- 16574476
TI  - Inner nuclear membrane and regulation of Smad-mediated signaling.
AB  - Smads mediate signal transduction by cytokines of the transforming growth factor
      beta family. Recent data show that intrinsic and extrinsic proteins of the inner
      nuclear membrane affect the activities of Smads. MAN1, an integral protein of the
      inner nuclear membrane, binds to receptor-regulated Smads and antagonizes
      signaling by transforming growth factor-beta, activin and bone morphogenic
      protein. Lamins A and C, extrinsic intermediate filament proteins of the inner
      nuclear membrane that are mutated in several human diseases, appear to regulate
      phosphorylation of Smads. These data demonstrate that proteins within and
      associated with the inner nuclear membrane lipid bilayer regulate signal
      transduction pathways involved in numerous developmental, physiological and
      pathophysiological processes.

PMID- 16574477
TI  - Nuclear protein kinase C.
AB  - Protein kinase C (PKC) isozymes constitute a family of ubiquitous
      phosphotransferases which act as key transducers in many agonist-induced
      signaling cascades. To date, at least 11 different PKC isotypes have been
      identified and are believed to play distinct regulatory roles. PKC isoforms are
      physiologically activated by a number of lipid cofactors. PKC is thought to
      reside in the cytoplasm in an inactive conformation and to translocate to the
      plasma membrane or cytoplasmic organelles upon cell activation by different
      stimuli. However, a sizable body of evidence collected over the last 20 years has
      shown PKC to be capable of translocating to the nucleus. Furthermore, PKC
      isoforms are resident within the nucleus. Studies from independent laboratories
      have to led to the identification of quite a few nuclear proteins which are PKC
      substrates and to the characterization of nuclear PKC-binding proteins which may
      be critical for finely tuning PKC function in this cell microenvironment. Several
      lines of evidence suggest that nuclear PKC isozymes are involved in the
      regulation of biological processes as important as cell proliferation and
      differentiation, gene expression, neoplastic transformation, and apoptosis. In
      this review, we shall highlight the most intriguing and updated findings about
      the functions of nuclear PKC isozymes.

PMID- 16574478
TI  - Adipocyte-type fatty acid-binding protein as inter-compartmental shuttle for
      peroxisome proliferator activated receptor gamma agonists in cultured cell.
AB  - We and others showed earlier that liver-type, epidermal-type and adipocyte-type
      (A-) fatty acid-binding proteins (FABPs) mediate peroxisome proliferator
      activated receptor (PPAR) dependent gene expression by channelling their ligand
      (fatty acid or drug) to the nuclear receptors via direct protein/protein
      interaction. To clarify mechanistic details of this signaling path, we address
      here A-FABP import into the nucleus and its interaction with PPARgamma. Making
      use of COS cells transfected with wild-type or mutant A-FABPs, we exclude
      posttranslational modification of A-FABP as import signal and provide evidence
      for both, ligand-dependent and ligand-independent nuclear translocation. With the
      aid of in vitro pull down assay we demonstrate that specific interaction of A
      FABP with PPARgamma isoforms does not require ligand. Moreover, A-FABP binds not
      only to the ligand-binding domain including hinge domain (domains DEF), but also
      to the DNA-binding domain including AB domains (domains ABC) of PPARgamma.

PMID- 16574479
TI  - Metabolism of arachidonic acid to eicosanoids within the nucleus.
AB  - The eicosanoids are a diverse family of molecules that have powerful effects on
      cell function. They are best known as intercellular messengers, having autocrine
      and paracrine effects following their secretion from the cells that synthesize
      them. Many of the eicosanoids are produced from one polyunsaturated fatty acid,
      arachidonic acid. The diversity of possible products that can be synthesized from
      arachidonic acid is due, in part to the variety of enzymes that can act on it.
      Over the past 15 years, studies have placed many, but not all, of these enzymes
      at or inside the nucleus. In some cases, the nuclear import or export of
      arachidonic acid-processing enzymes is highly regulated. Furthermore, nuclear
      receptors that are activated by specific eicosanoids are known to exist. Taken
      together, these findings indicate that the enzymatic conversion of arachidonic
      acid to specific signaling molecules can occur in the nucleus, that it is
      regulated, and that the synthesized products may act within the nucleus. The
      objectives of this commentary are to review what is known about the metabolism of
      arachidonic acid to eicosanoids within the nucleus and to point to important
      areas for future discovery.

PMID- 16574480
TI  - Nuclear inositide signalling -- expansion, structures and clarification.
AB  - The extent and content of this review issue highlights how our understanding of
      lipid signalling in the nucleus has grown, both in what we actually know, and the
      breadth of signalling pathways that we now have to consider. Here, a few key
      issues with regard to nuclear inositide signalling are briefly addressed.

PMID- 16574481
TI  - Ring-B functionalized androst-4-en-3-ones and ring-C substituted pregn-4-en-3
      ones undergo differential transformation in Aspergillus tamarii KITA: ring-A
      transformation with all C-6 substituted steroids and ring-D transformation with C
      11 substituents.
AB  - The fungus Aspergillus tamarii transforms progesterone 1 into testololactone 5 in
      high yield through a four-step enzymatic pathway which is flexible to a range of
      steroidal substrates. To date, no studies have investigated the fate of C-6 (ring
      B) and C-11 (ring-C) functionalized steroidal substrates on metabolism.
      Remarkably all of the C-6 functionalized substrates underwent reductive
      metabolism on ring-A in contrast to C-11 functionalized steroids where only ring
      D oxidative or reductive transformation occurred. In order to discern the precise
      role of the functional groups in directing metabolism 6-ketoprogesterone 10 with
      functionality at C-6 and the ring-D methyl ketone underwent reductive and
      oxidative transformation on both terminal A and D rings showing that this
      functionality was directing metabolism. Androst-4-en-3,6-dione 12 devoid of ring
      D functionality underwent reductive metabolism on ring-A proving that the C-6
      functionality was directing metabolism to this ring with the ring-D methyl ketone
      responsible for generating transformation at this position. Functionality at C-11
      exclusively controlled entry into and degree of metabolism on the lactonization
      pathway. These novel findings may have important bearing in the future
      understanding of structure activity relationships in revealing new metabolic
      pathways and further affords a unique opportunity for generation of novel
      bioactive steroidal compounds.

PMID- 16574482
TI  - A pilot randomised controlled trial of eccentric exercise to prevent hamstring
      injuries in community-level Australian Football.
AB  - Hamstring injuries are the most common injury sustained by Australian Football
      players. Eccentric training has been proposed as a potential preventative
      strategy. This pilot randomised controlled trial (RCT) evaluated the
      effectiveness of a pre-season eccentric training program for preventing hamstring
      injuries at the community level of Australian Football. Seven amateur clubs
      (n=220 players) were recruited. Players were randomised within clubs to the
      intervention (eccentric exercise) or control (stretching) groups and
      randomisation was stratified according to previous history of hamstring injury.
      Five exercise sessions were completed over a 12-week period, three during the pre
      season and two during the first 6 weeks of the season. Compliance was recorded
      and players were monitored for the season to collect injury and participation
      data. There was no difference between the control (n=106) or intervention (n=114)
      groups with respect to baseline characteristics. Only 46.8% of all players
      completed at least two program sessions. Compliance was poorest for the
      intervention group. Intention-to-treat analysis suggested that players in the
      intervention group were not at reduced risk of hamstring injury (RR 1.2, 95% CI:
      0.5, 2.8). When only control and intervention group players who participated in
      at least the first two sessions were analysed, 4.0% of intervention and 13.2% of
      control group players sustained a hamstring injury (RR 0.3, 95% CI: 0.1, 1.4;
      p=0.098). The findings suggest that a simple program of eccentric exercise could
      reduce the incidence of hamstring injuries in Australian Football but widespread
      implementation of this program is not likely because of poor compliance.

PMID- 16574483
TI  - Clustered data in sports research.
AB  - Clustered, or dependent, data, arise commonly in sports medicine and sports
      science research, particularly in studies of sports injury and biomechanics,
      particularly in sports injury trials that are randomised at team or club level,
      in cross-sectional surveys in which groups of individuals are studied and in
      studies with repeated measures designs. Clustering, or positive correlation among
      responses, arises because responses and outcomes from the same cluster will
      usually be more similar than from different clusters. Study designs with
      clustering will usually required an increased sample size when compared to those
      without clustering. Ignoring clustering in statistical analyses can also lead to
      misleading conclusions, including incorrect confidence intervals and p-values.
      Appropriate statistical analyses for clustered data must be adopted. This paper
      gives some examples of clustered data and discusses the implications of
      clustering on the design and analysis of studies in sports medicine and sports
      science research.

PMID- 16574484
TI  - The effect of intermittent hypoxic training via a hypoxic inhaler on
      physiological and performance measures in rowers: a pilot study.
AB  - Intermittent hypoxic training and discontinuous exposure to altitude were used to
      improve performance at sea level in elite rowers. Altitude was simulated with a
      newly patented device which allowed athletes to experience altitude by re
      breathing oxygen-depleted expired air. Seven elite rowers (five females, two
      males) used inhalers for a 90-min supervised daily session (alternating 6 min on
      and 4 min off) for 3 weeks, while four female elite rowers used placebo devices
      in the same sessions. The inhalers were adjusted to produce a progressive
      decrease in oxygen saturation over the 3 weeks (initially 90%; finally 80%).
      Immediately before and 7-10 days after altitude exposure, the rowers performed an
      incremental lactate test to determine power output equivalent to 4 mM [BLa], a
      500-m time trial and a 5000-m time trial, all on a rowing ergometer. Relative to
      the control group, the altitude group showed a slight improvement in mean power
      for the 5000-m time trial (0.6%, 90% likely limits +/-3.7%), and a substantial
      impairment in mean power for the 500-m trial (2.2%, +/-4.1%). Power at 4-mM
      lactate declined in both groups, but overall the altitude group improved by 0.4%
      (+/-3.5%) relative to control. The device represents a practical way to simulate
      altitude exposure, but it is unlikely to have major effects on performance of
      elite rowers.

PMID- 16574486
TI  - Ions, energy and axonal injury: towards a molecular neurology of multiple
      sclerosis.
AB  - It is now clear that effective treatments for nervous system disorders such as
      multiple sclerosis (MS) represent achievable objectives. Molecular mechanisms of
      axonal degeneration - a major pathological substrate for disability in MS - have
      been identified, pointing to the possibility of neuroprotection. Although
      previous studies were mainly carried out in laboratory models, recent analyses of
      human MS tissue have identified molecular targets that are related to
      mitochondrial function and specific isoforms of ion channels as contributors to
      axonal degeneration in MS. Taken together, the observations in model systems and
      in human tissue converge on the identification of a group of molecules that are
      related to ion fluxes and energetics as significant actors in the axonal-injury
      cascade, and suggest a set of molecular targets that might be useful in the
      development of new therapies.

PMID- 16574487
TI  - Proceedings of the International Workshop on Tuberculosis Vaccines May 8-12,
      2005, Varadero, Matanzas, Cuba.

PMID- 16574488
TI  - The combined effect of platelet storage media and intercept pathogen reduction
      technology on platelet activation/activability and cellular apoptosis/necrosis:
      Lisbon-RBS experience.
AB  - Platelets are known to undergo shape change, activation, a release reaction and
      apoptosis/necrosis during processing and storage, all of which are collectively
      known as the platelet storage lesion. Any additional processing may have some
      deleterious impact on platelet activability and functional integrity, which need
      to be investigated. This preliminary investigation was undertaken to establish
      the combined effects of standard platelet storage media and the intercept
      pathogen reduction technology on platelet activation and activability during 7
      day storage, using buffy-coat derived platelets in standard storage media
      containing 35% plasma (N=24). P-selectin (CD62p) expression, a classical marker
      of platelet activation, and phosphatidylserine (PS) exposure on the platelet
      surface membrane, a hallmark of cellular necrosis/apoptosis, were both measured
      by flow cytometry. The results reveal significant increases in activation, from
      an average of 22.7% on day 1 before treatment to 31.6% on day 2 after treatment
      and 58.7% at the end of storage. Concomitantly, the basal expression of PS was
      slightly increased from 1.9% to 2.8% at day 2 after treatment and 7.3% at the end
      of storage. However, the functional reserve of platelets during storage, which
      reflects their capability to undergo activation and the release reaction when
      platelets were challenged with either calcium ionophore or thrombin, was
      relatively well maintained. These preliminary data confirm the earlier data on
      the use of intercept, and for the first time, based on the assessment of platelet
      functional integrity, suggest that platelet functional reserve is relatively well
      maintained, with little change in the formation of apoptotic cells.

PMID- 16574489
TI  - Donor selection criteria to maximize double platelet products (DPP) by platelet
      apheresis.
AB  - Variant Creutzfeldt-Jakob disease brought us to perform a study to diminish donor
      exposure from transfusion of platelet concentrates. The current study aimed to
      develop donor selection criteria that maximize the likelihood of deriving single
      donor platelets and producing double platelet products (DPP). Donors were
      recruited among plasmapheresis donors and among other donors when the selected
      donors did not show up. Donor precount and body weight and haematocrit were
      examined as determinants of higher split-rates combined with procedure time. When
      the criterion was set on 225; 82% of the procedures (n=717) with a precount of
      >225 yielded DPP compared to 54% of the procedures with a precount <225 (p<.01).
      Body weight >65 kg gave good results in split-rate. Procedure time showed an
      inverse correlation with the highest correlating precount (r=-.14; p<.001).
      Eighty one percent of the donors reported a willingness to donate at least seven
      times a year and 75% accepted the mean procedure time. This confirmed logistical
      feasibility of the conversion to AP-PC although profits would be reduce 13%
      compared to platelets from pooled buffy coats.

PMID- 16574490
TI  - Dendritic cell-based tumor vaccines and antigen presentation attenuators.
AB  - Dendritic cell (DC)-based tumor vaccines are being extensively tested to treat
      cancer patients. Although the results of most DC-based clinical trials have been
      disappointing, recent advances in the basic molecular understanding of positive
      and negative regulation of antigen presentation and immune responses can form a
      basis to enhance the efficacy of DC-based vaccines. Here we describe the new
      understanding of the importance of Toll-like receptor, tumor necrosis factor
      receptor, and cytokine receptor signaling in activation of innate and adaptive
      immunity. In particular, we describe the emerging importance of hardwired
      negative regulators, such as cytokine signaling regulators, as antigen
      presentation attenuators (APAs), providing a new strategy to break self-tolerance
      and enhance the potency of tumor vaccines by inhibiting APAs.

PMID- 16574491
TI  - Highly efficient regulation of gene expression by tetracycline in a replication
      defective herpes simplex viral vector.
AB  - Employing the tetracycline repressor tetR and the wild-type hCMV major immediate
      early promoter, we have developed a highly sensitive tetracycline-inducible
      transcription switch in mammalian cells (T-REx; Invitrogen, Carlsbad, CA, USA).
      In view of the previous difficulty in achieving regulatable gene expression in
      recombinant HSV vector systems, we constructed a T-REx-encoding replication
      defective HSV-1 recombinant, QR9TO-lacZ, that encodes two copies of the tetR gene
      controlled by the HSV-1 immediate-early ICP0 promoter and a reporter, the LacZ
      gene, under the control of the tetO-bearing hCMV major immediate-early promoter.
      Infection of cells, such as Vero, PC12, and NGF-differentiated PC12 cells, with
      QR9TO-lacZ led to 300- to 1000-fold tetracycline-regulated gene expression.
      Moreover, the expression of the LacZ gene by QR9TO-lacZ can be finely controlled
      by tetracycline in a dose-dependent fashion. Efficiently regulated gene
      expression can also be achieved in vivo following intracerebral and footpad
      inoculations in mice. The demonstrated capability of T-REx for achieving high
      levels of sensitively regulated gene expression in the context of the HSV-1
      genome will significantly expand the utility of HSV-based vector systems for
      studying gene function in the nervous system and delivering regulated gene
      expression in therapeutic applications, particularly in the treatment of CNS
      diseases.

PMID- 16574492
TI  - Oncolytic viruses derived from the gamma34.5-deleted herpes simplex virus
      recombinant R3616 encode a truncated UL3 protein.
AB  - Replication-competent herpes simplex virus (HSV-1) mutants are used in clinical
      trials in the experimental treatment of cancer. Mutants G207, HSV1716, NV1020,
      and Oncovex GM-CSF share in common a defect in one or both copies of the gene
      encoding the neurovirulence factor, ICP34.5, and are thus neuroattenuated. These
      viruses are acknowledged to differ from one another (a) in the specific types of
      mutations intentionally introduced during their derivation and (b) in the
      inherent genetic differences retained from the different parent strains used in
      their construction. Unintended mutations are expected to emerge at some low
      frequency during the selection for and passage of mutant viruses. Here we
      demonstrate that during the construction of the oncolytic virus R3616, a nonsense
      mutation arose in an untargeted region of the HSV-1 genome that resulted in a
      substantial truncation of the viral protein known as UL3. This report is the
      first published documentation that oncolytic herpesviruses developed and used in
      clinical trials contain adventitious mutations. The implications of these
      findings for the characterization and development of vectors proposed for use in
      clinical trials are discussed.

PMID- 16574493
TI  - Age-dependent effects on redox status, oxidative stress, mitochondrial activity
      and toxicity induced by fluoroquinolones on primary cultures of rabbit tendon
      cells.
AB  - The age-related difference in fluoroquinolone-induced tendon toxicity was
      investigated. In vitro tendon cells from juvenile and young adult rabbits,
      respectively, were incubated with quinolone (nalidixic acid, NA) or
      fluoroquinolone (ofloxacin, OFX or pefloxacin, PEF) at 0.01 microM to 1 mM for 72
      h. Redox status, glutathione (GSH), reactive oxygen species (ROS), and
      mitochondrial activity were assessed using intracellular fluorescent probes.
      Fluorescence signal was detected on living adherent tenocytes in microplates
      using cold-light cytofluorometry. Tendon toxicity differed significantly between
      the two cell groups and the difference was greatest with highest dose (1 mM). For
      72 h, significant (p < 0.001) differences between immature and young adult
      primary tenocytes were observed for redox status decrease, GSH decrease, and ROS
      production increase. Mitochondrial activity remained unaltered in immature
      tenocytes. We confirm two groups of intrinsic tendon toxicity (OFX/NA vs. PEF)
      associated to oxidative stress (GSH decrease). Our in vitro experimental model
      confirms the clinical observations of age dependent tenotoxicity. First group
      (NA, OFX) showed greater intrinsic tenotoxicity for young adult than immature
      tenocytes, second group (PEF) was highly toxic for immature and young adult
      cells. The three quinolones do not altered mitochondrial activity in immature
      tenocytes whereas alteration was observed in young adult tenocytes.

PMID- 16574494
TI  - Data integration and genomic medicine.
AB  - Genomic medicine aims to revolutionize health care by applying our growing
      understanding of the molecular basis of disease. Research in this arena is data
      intensive, which means data sets are large and highly heterogeneous. To create
      knowledge from data, researchers must integrate these large and diverse data
      sets. This presents daunting informatic challenges such as representation of data
      that is suitable for computational inference (knowledge representation), and
      linking heterogeneous data sets (data integration). Fortunately, many of these
      challenges can be classified as data integration problems, and technologies exist
      in the area of data integration that may be applied to these challenges. In this
      paper, we discuss the opportunities of genomic medicine as well as identify the
      informatics challenges in this domain. We also review concepts and methodologies
      in the field of data integration. These data integration concepts and
      methodologies are then aligned with informatics challenges in genomic medicine
      and presented as potential solutions. We conclude this paper with challenges
      still not addressed in genomic medicine and gaps that remain in data integration
      research to facilitate genomic medicine.

PMID- 16574495
TI  - A potential role for sildenafil in the management of pulmonary hypertension in
      patients with parenchymal lung disease.
AB  - BACKGROUND: Sildenafil offers potential to treat patients with pulmonary
      hypertension by selectively inhibiting phosphodiesterase type five pathways in
      the lung. It is recommended for selected patients with pulmonary arterial
      hypertension, but its role in the management of pulmonary hypertension associated
      with parenchymal lung disease is unclear. PATIENTS AND METHODS: Seven patients
      (68-86 years) with end stage chronic obstructive pulmonary disease (COPD, 4) and
      idiopathic pulmonary fibrosis (IPF, 3) were referred to our unit. All patients
      had a long-term history of chronic lung disease and were on maximal appropriate
      therapy prescribed by their referring pulmonologist. Thromboembolic disease was
      excluded by pulmonary angiography and all patients had had high resolution
      thoracic CT scan. At assessment right heart catheterisation, 2D echocardiography
      and 6-min walk test were performed prior to commencement of sildenafil 50mg tds.
      Their medication was otherwise unchanged. After 8 weeks treatment, right heart
      catheterisation, 2D echocardiography and 6-min walk test were repeated. RESULTS:
      The pulmonary vascular resistance was reduced in six patients (from 13, 3, 3,
      6.5, 3.5 and 10.5 wood units to 9.7, 2.5, 2.8, 4.4, 2.5 and 5.4 wood units,
      respectively). Six-minute walk test increased in six patients (from 110 m, 210 m,
      80 m, 30 m, 210 m and 80 m to 130 m, 312 m, 120 m, 82 m, 244 m and 100 m,
      respectively). One patient with COPD did not demonstrate a favourable response
      although their cardiac output increased on sildenafil therapy. 2D
      echocardiography showed a reduction in estimated PA pressure in six patients with
      an improvement in right ventricular systolic function in two COPD patients.
      CONCLUSION: Our results suggest that sildenafil may have a role for selected
      patients with COPD and IPF who have pulmonary hypertension.

PMID- 16574497
TI  - Comparing classifications of death in the Mode Selection Trial: agreement and
      disagreement among site investigators and a clinical events committee.
AB  - Clinical events committees (CECs) are the current standard for endpoint
      adjudication in clinical trials. However, little data exist with which to compare
      CEC and site investigator determinations or to evaluate internal agreement among
      CEC members. Using data from the Mode Selection Trial in Sinus Node Dysfunction
      (MOST), we analyzed classifications of death in order to compare internal
      agreement among CEC physician reviewers and agreement between the CEC and site
      investigators. Death was classified at 2 levels: by major cause (cardiac,
      noncardiac, or unknown) and by minor subclassification of the major
      classifications. Reviewer agreement was tabulated at the major and minor levels,
      and standard and weighted kappa statistics were calculated. Disagreement at both
      levels was also determined. Individual decision-making was tabulated in terms of
      frequency in classifying death as unknown. All 404 deaths were classified by the
      CEC. Site investigators determined major classifications in 382 cases and minor
      classification in 379 cases. The CEC and the site investigators disagreed in
      classifying 41 cases (10.7%) at the major level and 117 (30.9%) at the minor
      level. CEC reviewers disagreed internally at the major level in 64 cases (15.8%),
      at the minor level in 63 cases (15.6%), and at any level in 127 cases (31.4%)
      (kappa = 0.60, 95% confidence interval (CI) [0.55, 0.66]; weighted kappa = 0.66,
      95% CI [0.62, 0.75]). In resolving internal disagreements, the full CEC agreed
      with 1 of 2 CEC reviewers in 85.9% of cases. Disagreements occurred between site
      investigators and CEC reviewers in classifying deaths. Endpoint determination and
      decision-making varied among individual CEC reviewers, but second-tier reviews by
      the full CEC resolved all disagreements. These findings support continued use of
      CECs for endpoint adjudication in clinical trials.

PMID- 16574496
TI  - Blunted non-nitric oxide vasodilatory neurotransmission in penile arteries from
      renal hypertensive rats.
AB  - The present study was designed to explore whether there are any effects on
      neurogenic responses in penile small arteries during the development of
      hypertension in a one-kidney, one-clip (1K1C) model, a non-renin-dependent model
      of renovascular hypertension. Five weeks after surgery, male Sprague-Dawley rats
      were given vehicle, bendroflumethiazide (7.5 mg/kg/day), or L-arginine (2
      g/kg/day) in their drinking water for five weeks. Experiments were performed on
      penile small artery rings (150-200 microm) mounted on microvascular myographs for
      electrical field stimulation (EFS), and erectile tissue was processed for
      immunohistochemistry. Maximal neurogenic contractions were unmodified in penile
      preparations. Relaxations induced by EFS were reduced in the presence of ADMA. In
      1K1C rats, neurogenic vasorelaxation mediated by nitric oxide (NO) was unaltered,
      while relaxation resistant to NO synthase inhibition was blunted. L-arginine and
      bendroflumethiazide lowered blood pressure in 1K1C rats, but vasodilation was
      still blunted in the penile arteries. Immunoreactivity for factor VIII and
      neuronal NO synthase was unaltered in penile arteries from 1K1C animals.
      Endothelium-dependent vasorelaxation evoked by acetylcholine was also blunted in
      preparations from 1K1C rats, while exogenous NO relaxation was unaffected. Plasma
      concentrations and urinary excretion of ADMA did not differ among the
      experimental animals. Our findings indicate that the reduced release of a non-NO
      vasodilatory neurotransmitter accounts for the impaired neurogenic vasodilation
      of the penile arteries. Although ADMA inhibits penile vasorelaxation, it is
      unlikely to affect erectile function in 1K1C rats.

PMID- 16574498
TI  - Pancreatobiliary afferent recordings in the anaesthetised Australian possum.
AB  - The sensory innervation to the pancreatobiliary system is poorly characterized.
      Afferent signals from the gastrointestinal tract and biliary tree are transmitted
      to the central nervous system via the vagus and spinal nerves. We aimed to record
      afferent discharge in order to characterize the vagal and splanchnic afferent
      signals from the possum upper gastrointestinal tract, biliary tree and pancreas.
      In 21 anaesthetised possums nerve fibres were teased from the vagus or splanchnic
      nerve for multi-unit recording. Mechanical stimuli consisted of balloon
      distension of the gallbladder and duodenum (2-7 ml) and fluid distension (0-20 mm
      Hg) of the bile or pancreatic ducts. Approximately 60% of fibres from all nerves
      displayed spontaneous discharge. Spinal afferent responses to mechanical stimuli
      were infrequent (n=13). Increased discharge occurred in response to duodenal
      (12/99 fibres) or gallbladder (7/96 fibres) distension, but not to bile duct
      (0/73 fibres) or pancreatic duct (0/51 fibres) distension. Vagal afferent
      responses to distension of the duodenum or stomach (5-30 ml) were more common
      (n=8). Increased discharge was recorded in response to duodenal (49/134 fibres),
      or gastric (22/70 fibres) distension. Responses to gallbladder distension were
      less frequent (6/99 fibres) and as with the spinal afferent no response to bile
      duct (0/66) or pancreatic duct (0/70) distension were recorded. We conclude that
      mechanosensitive afferents in the pancreatobiliary system are relatively rare,
      particularly within the ducts, and/or that they are adapted to monitor stimuli
      other than luminal distension.

PMID- 16574499
TI  - Multiple components of the defense response depend on orexin: evidence from
      orexin knockout mice and orexin neuron-ablated mice.
AB  - Stressor induces not only cognitive, emotional and behavioral changes but also
      autonomic changes. Although research on the neural circuits underlying such
      autonomic changes has implicated the hypothalamus in the defense response against
      stressors, neurotransmitters in this multifaceted and coordinated response have
      not been revealed. In this brief review, here we summarize our recent discovery
      using orexin knockout mice and orexin neuron-ablated mice of possible
      contribution of orexin in the defense response and discuss future directions.

PMID- 16574500
TI  - Automatic positioning of a microinjector in mouse ES cells and rice protoplasts.
AB  - A 2-channel (2C) microinjector was prepared by pulling a glass capillary with a
      theta-shaped cross section. One channel was used as a potential measuring
      electrode (MeaE) and the other was used as an electrophoretic introduction
      electrode (IntE). The 2C microinjector was propelled by an oil pressure
      manipulator driven by a pulse motor, while the MeaE output was recorded
      continuously. When the 2C microinjector penetrated the cell membrane of a mouse
      ES cell or a rice protoplast, the output potential changed sharply. The
      differential of this potential change was used as a stop signal for the pulse
      motor. Thus, the microinjector was correctly positioned in the cell without
      losing cell viability. Its success rate was 73% and 84% for ES cells and rice
      protoplasts, respectively. After the positioning of the microinjector in the
      cell, Lucifer yellow (LY) was introduced via IntE. Under these conditions, the
      rate of viable cells was 16% and 62% for ES cells and rice protoplasts,
      respectively.

PMID- 16574501
TI  - Poor base stacking at DNA lesions may initiate recognition by many repair
      proteins.
AB  - A fundamental question in DNA repair is how a mismatched or modified base is
      detected when embedded in millions to billions of normal base pairs. A survey of
      the literature and structural database reveals a common feature in all repair
      protein-DNA complexes: the DNA double helix is discontinuous at a lesion site due
      to base unstacking, kinking and/or nucleotide extrusion. Lesions induce
      destabilization and distortion of short linear DNAs, and underwinding in
      negatively supercoiled DNA presumably could compound the reduced stability caused
      by a lesion. A hypothesis is thus put forward that DNA lesion recognition occurs
      in two steps. Repair proteins initially recognize the weakened base stacking, and
      thus a flexible hinge at a DNA lesion. Sampling of flexible hinges rather than
      all DNA base pairs can reduce the task of finding a lesion by two to three orders
      of magnitude, from searching millions base pairs to thousands. After the initial
      encounter, a repair protein scrutinizes the shape, hydrogen bonding and
      electrostatic potentials of bases at the flexible hinge and dissociates if it is
      not a correct substrate. MutS, which has a broad range of substrates, actively
      dissociates from non-specific binding via an ATP-dependent proofreading
      mechanism. A single lesion may thus be sampled by BER, NER and MMR proteins until
      repaired. This proposition immediately suggests a mechanism for crosstalk between
      different repair and signaling pathways. It also raises the possibility that
      sampling of a lesion by one protein could facilitate loading of another by direct
      protein-protein or DNA mediated interactions.

PMID- 16574502
TI  - Stem cells and cystic fibrosis.
AB  - Although cystic fibrosis at first sight appears to be one of the most obvious
      human diseases to treat with gene therapy, since it is caused by a single-gene
      defect and the main affected organ is the lung which is relatively easily
      accessible, clinical results have thus far been disappointingly limited. At least
      one cause for this lack of success is the failure to permanently correct the gene
      defect in addition to the rapid turnover of lung epithelial cells. Alternative
      approaches therefore involve the search for and use of stem cell populations.
      This review presents an overview of recent attempts to identify lung- or bone
      marrow-derived populations of stem cells or progenitor cells and to apply such
      cells, heterologous or gene-corrected autologous, to colonize the airways while
      differentiating into functional respiratory columnar epithelial cells. The most
      successful approaches thus far appear to be obtained with bone marrow-derived
      cells such as mesenchymal stem cells, although the transdifferentiation rate thus
      far has been limited to below the 1% level. As an alternative the proven
      multipotent nature of bronchioalveolar stem cells isolated from lung tissue may
      provide another promising approach for successful stem cell therapy.

PMID- 16574503
TI  - Respiratory cooling and thermoregulatory coupling in reptiles.
AB  - Comparative physiological research on reptiles has focused primarily on the
      understanding of mechanisms of the control of breathing as they relate to
      respiratory gases or temperature itself. Comparatively less research has been
      done on the possible link between breathing and thermoregulation. Reptiles
      possess remarkable thermoregulatory capabilities, making use of behavioural and
      physiological mechanisms to regulate body temperature. The presence of thermal
      panting and gaping in numerous reptiles, coupled with the existence of head-body
      temperature differences, suggests that head temperature may be the primary
      regulated variable rather than body temperature. This review examines the
      preponderance of head and body temperature differences in reptiles, the
      occurrence of breathing patterns that possess putative thermoregulatory roles,
      and the propensity for head and brain temperature to be controlled by reptiles,
      particularly at higher temperatures. The available evidence suggests that these
      thermoregulatory breathing patterns are indeed present, though primarily in arid
      dwelling reptiles. More importantly, however, it appears that the respiratory
      mechanisms that have the capacity to cool evolved initially in reptiles, perhaps
      as regulatory mechanisms for preventing overheating of the brain. Examining the
      control of these breathing patterns and their efficacy at regulating head or
      brain temperature may shed light on the evolution of thermoregulatory mechanisms
      in other vertebrates, namely the endothermic mammals and birds.

PMID- 16574504
TI  - Liquid chromatography electrospray ionization mass spectrometry analysis of the
      ocular metabolites from a short interfering RNA duplex.
AB  - The ocular metabolism of an siRNA duplex, SIRNA-027, was examined by ion-pair
      reversed-phase liquid chromatography (IP-RP-LC) coupled to electrospray
      ionization mass spectrometry (ESI-MS). The RNA duplex was injected intraocularly
      into the eyes of New Zealand white rabbits. Rabbits were sacrificed at different
      timepoints and the vitreous and retina/choroid tissue analyzed for siRNA by IP-RP
      LC-MS. The method used a hexafluoroisopropanol (HFIP)/triethylamine (TEA) ion
      pairing buffer with a methanol gradient. Using electrospray ionization, the
      duplex was preserved in the gas phase for analysis by a triple quadrupole mass
      spectrometer. With this methodology metabolites from rabbit ocular vitreous humor
      and retina/choroid tissue were identified and a pattern of siRNA degradation was
      established. Results showed that the duplex was metabolized predominantly from
      one end. This end of the siRNA duplex was calculated to have the weakest binding
      energy of the two ends indicating that the ability of the siRNA to split into
      single strands is a factor in its degradation.

PMID- 16574505
TI  - Simultaneous determination of nitroglycerin and dinitrate metabolites in
      metabolism studies using liquid chromatography-mass spectrometry with
      electrospray ionization.
AB  - We have developed a liquid chromatographic-mass spectrometric method for the
      simultaneous determination of nitroglycerin (NTG) and its active metabolites,
      glyceryl 1,2-dinitrate (1,2-GDN) and glyceryl 1,3-dinitrate (1,3-GDN), for
      metabolism studies in cell cultures. 1,2,4-Butanetriol-1,4-dinitrate was chosen
      as an internal standard. Using a linear gradient of water/methanol containing
      0.025 mM NH(4)Cl, the compounds were eluted within 12.5 min on an Allure Aqueous
      C(18) column (100 mm x 2.1 mm). Detection and quantification was achieved with
      multiple reaction monitoring in the negative ion mode. Intra- and inter-day
      variabilities for simultaneous determination of the three nitrates were below 10
      and 18%, respectively, over a range of NTG and GDN concentrations of 0.5-15
      ng/ml. The lower limit of quantification was found to be about 0.01 ng on column.
      Application of this method was illustrated through in vitro metabolism studies of
      NTG in culture media bathing LLC-PK1 cells and human vascular smooth muscle cells
      (HA-VSMC) at 37 degrees C. The degradation half-life of NTG was found to be 4.5
      +/- 0.4 h and 39.2 +/- 0.02 h, respectively, for LLC-PK1 cells versus HA-VSMC. At
      5 h, the 1,2-GDN versus 1,3-GDN metabolite distribution ratio in the bathing
      medium was found to be 1.5 +/- 0.1 and 0.2 +/- 0.02 for LLC-PK1 and HA-VSMC
      cells, respectively. With this method, the degradation half-life of NTG in rat
      plasma at 37 degrees C was shown to be 26.8 +/- 1.8 min, consistent with previous
      values obtained using gas chromatography.

PMID- 16574506
TI  - High-performance liquid chromatographic determination of the magnetic resonance
      imaging contrast agent Gadocoletate ion in human plasma, urine and faeces.
AB  - Gadocoletate ion is a new paramagnetic intravascular contrast agent for magnetic
      resonance imaging (MRI). An high-performance liquid chromatographic method for
      assaying Gadocoletate ion in human plasma, urine and faecal samples is described.
      The analysis is based on the reversed-phase chromatographic separation of
      Gadocoletate ion from the endogenous components of the biological matrices and
      its detection during elution by ultraviolet light absorption at 200 nm. The
      selectivity of the method was satisfactory. The mean absolute recovery during the
      analytical sample preparation was greater than 87%. The precision, expressed as
      coefficient of variation (CV%) ranged from 0.29 to 5.90% and the accuracy,
      expressed as mean relative error (R.E.%) of the analytical method ranged from 
      3.7 to +7.1%. The detection limit in plasma and urine was 2.01 and 10.0 microg/mL
      (0.00203 and 0.0101 micromol/mL), respectively. The detection limit in
      homogenized faecal samples was 17.7 microg/g (0.0179 micromol/g). Stability
      studies were performed in human plasma and urine samples during the analytical
      cycle. Gadocoletate ion was shown to be stable in human plasma and in human urine
      when stored at about +4 degrees C for up 24 h, and after three freeze-thaw
      cycles. In addition, it was shown to be stable in samples of processed plasma and
      in diluted urine at about +4 degrees C for 48 h, and at room temperature for at
      least 24 h. As regards the long-term stability of Gadocoletate ion, the results
      of dedicated studies showed that Gadocoletate ion is stable in human plasma
      samples when stored at +4 degrees C for up to 30 days and at -80 degrees C for up
      to 90 days. Gadocoletate ion is stable in samples of human urine when stored at
      +4 degrees C for up to 30 days, and when stored at -20 degrees C and at -80
      degrees C for up to 90 days. The method has been successfully validated in human
      plasma, urine and faeces and it has been shown to be precise, accurate and
      reliable.

PMID- 16574507
TI  - Determination of endogenous testosterone in rat tissues following fetal alcohol
      exposure using HPLC with UV detection.
AB  - A novel method for quantitation of brain neurosteroid levels using HPLC with UV
      detection is described. In this simple and reliable method, testosterone from the
      brain and whole blood, and the internal standard, 17alpha-methyl testosterone,
      were extracted in 20% acetonitrile-phosphate buffer (pH 2.8), followed by solid
      phase extraction (SPE). The calibration curve was linear in concentration ranges
      from 0.1 to 10 ng from 0.2 g of tissue. We successfully applied this method to
      the analysis of endogenous testosterone in the male offspring of rats exposed to
      alcohol in utero. The concentration of testosterone at 21 post delivery in fetal
      alcohol exposure (FAE) group was significantly greater than the concentrations in
      either pair-fed or the ad libitum controls. These results support the usefulness
      of this method as a means of quantitating neurosteroids, and illustrate its
      applicability to fetal alcohol exposure.

PMID- 16574508
TI  - Sensitive high-performance liquid chromatographic quantitation of gabapentin in
      human serum using liquid-liquid extraction and pre-column derivatization with 9
      fluorenylmethyl chloroformate.
AB  - Most of the published methods for analysis of gabapentin, an antiepileptic agent,
      in human serum are based on the same approach, involving o-phthaldialdehyde
      derivatization of deproteinized serum samples. The present paper however,
      describes a new, simple and sensitive high-performance liquid chromatographic
      method for determination of gabapentin in human serum using liquid-liquid
      extraction and 9-fluorenylmethyl chloroformate (FMOC-Cl) as pre-column labeling
      agent. The drug and an internal standard (azithromycin) were extracted from serum
      by salting-out approach using a mixture of dichloromethane-2 propanol (1:1, v/v)
      as the extracting solvent. The extracted analytes were subjected to
      derivatization with FMOC-Cl in the presence of phosphate buffer (pH 7). A mobile
      phase consisting of methanol-0.05 M sodium phosphate buffer (73/27, v/v; pH of
      3.9) containing 1 ml/l triethylamine was eluted and chromatographic separation
      was performed on a Shimpack CLC-C18 (150 mm x 4.6 mm) column. The standard curve
      was linear over the range of 0.03-20 microg/ml and limit of quantification was
      0.03 microg/ml. The performance of analysis was studied and the validated method
      showed excellent performance in terms of selectivity, specificity, sensitivity,
      precision and accuracy. No interferences were found from commonly co-administered
      antiepileptic agents.

PMID- 16574509
TI  - Determination of enzymatic activity by capillary electrophoresis.
AB  - Enzymes are biological catalysts that play an important role in biochemical
      reactions necessary for normal growth, maturation and reproduction through whole
      live world. Their accurate quantitation in biological samples is important in
      many fields of biochemistry, not only in routine biochemistry and in fundamental
      research, but also in clinical and pharmacological research and diagnosis. Since
      the direct measurement of enzymes by masses is impossible, they must be
      quantified by their catalytic activities. Many different methods have been
      applied for this purpose so far. Although photometric methods are undoubtedly the
      most frequently used, separation methods will further gain their position in this
      field. The article reviews different possibilities for the assay of enzymatic
      activity by means of capillary electrophoresis (CE). Both the off-line and on
      line enzyme assays based on CE are discussed.

PMID- 16574510
TI  - Direct comparison between ion-exchange chromatography and aqueous two-phase
      processes for the partial purification of penicillin acylase produced by E. coli.
AB  - A direct comparison of a chromatography and an aqueous two-phase system (ATPS)
      processes for the partial purification of penicillin acylase (PA) produced by a
      recombinant strain of E. coli, was performed. An established chromatography
      process for the recovery of PA was selected as a model system and characterised
      for comparison with a developed ATPS prototype process. PEG-phosphate systems
      were selected for the recovery of PA over PEG-citrate systems, since higher
      enzyme recovery and increased purity was obtained. ATPS proved to be suitable to
      process highly concentrated disrupted extract (35%, w/w) and maintain a high top
      phase enzyme recovery. In the direct comparison of the processes, the superiority
      of the ATPS approach was highlighted since a reduction of the number of unit
      operations from 7 to 4 was achieved. An outline economic analysis based on the
      cost of separation agent of the processes favour the ATPS process, in which a
      gross cost reduction of 37% (from 0.47 to 0.30 US dollars) was achieved. Such
      result was obtained considering a potential re-use of up to 100 times of the
      resin used in the chromatography process. Additionally, by assuming that all the
      unit operations are equivalent in investment and operating cost, further
      reduction of approximately 43% of the respectively involved cost can be obtained
      when the ATPS process is used. Overall, the proposed ATPS process comprising of
      PEG1450-phosphate, tie-line length (TLL) of 48.5% (w/w), volume ratio (Vr) of
      1.0, pH of 7.0 and 35% (w/w) PA crude extract loaded into the system proved to be
      more efficient, recovering 97% of PA at the top phase (PEG rich phase) with a
      purity factor of 3.5. It is clear that the results reported herein raise the
      consideration for the potential substitution of the chromatography process for PA
      recovery from E. coli as a first step for the development of an optimised and
      economic process with evident commercial application.

PMID- 16574511
TI  - Application of L-Amino acid in determination of Huperzine A by high performance
      liquid chromatography.
AB  - A selective HPLC method for determination of Huperzine A in Huperzia serrata
      Extract has been developed and validated. Huperzine A was dissolved in 0.01 mol/L
      HCl, chromatographed on an Agilent Zorbax SB-C18 (150 mm x 4.6 mm i.d., 5 microm)
      column, with a mobile phase consisting of methanol-1mM L-Lysine water solution
      (50:50, v/v), and detected at 310 nm. The UV peak areas were used for
      quantitation of Huperzine A content. The correlation coefficient (R(2)) of the
      calibration was 0.9999 over the range of 1-25 microg/ml and intra- and interday
      precision over this range were not more than 2%. The method was successfully
      applied to characterize and determine the Huperzine A in Huperzia serrata
      Extract.

PMID- 16574512
TI  - Simple and rapid liquid chromatography method for determination of efavirenz in
      plasma.
AB  - A simple and rapid high performance liquid chromatographic method for
      determination of efavirenz in human plasma was developed. The method involved
      extraction of sample with ethyl acetate and analysis using a reversed-phase C(18)
      column (150 mm) with UV detection. The assay was linear from 0.0625 to 10.0
      microg/ml. The method was specific for efavirenz estimation and the drug was
      stable in plasma up to one month at -20 degrees C. The average recovery of
      efavirenz from plasma was 101%. Due to its simplicity, the assay can be used for
      pharmacokinetic studies and therapeutic drug monitoring of efavirenz.

PMID- 16574513
TI  - Isolation and characterization of an apoptotic and platelet aggregation
      inhibiting L-amino acid oxidase from Vipera berus berus (common viper) venom.
AB  - An L-amino acid oxidase was isolated from the venom of the common viper Vipera
      berus berus by a three-step procedure combining gel filtration, ion exchange and
      hydrophobic chromatography. The enzyme is a non-covalently bound homodimer with a
      monomeric molecular mass of 57.7 kDa. The N-terminal amino acid sequence and the
      internal peptide sequences show close structural homology with other snake venom
      L-amino acid oxidases. The purified protein catalyzed oxidative desamination of L
      amino acids, the most specific substrate is L-Phe. The best substrates among the
      studied 20 amino acids were: L-Met, L-Leu, L-Phe, L-Ile, L-Arg and L-His. Five
      amino acids, L-Ser, L-Pro, Gly, L-Thr and L-Cys, were not oxidized. The enzyme
      inhibited ADP-induced platelet aggregation dose-dependently with an IC50 of 0.07
      microM. The effect was neutralized by catalase. V. berus berus LAAO induced
      apoptosis in cultured HeLa and K562 cells as shown by DNA fragmentation gel
      pattern. The induction of apoptosis was inhibited by catalase.

PMID- 16574514
TI  - Nutritional therapy in paediatric Crohn's disease: More food for thought?

PMID- 16574515
TI  - Metal stent placement in acute malignant colorectal obstruction.
AB  - BACKGROUND: Obstruction is a common complication of advanced colorectal cancer.
      Stent insertion can reduce the need for emergency surgery and allows chemotherapy
      to begin immediately. AIMS: To evaluate the technical and clinical success and
      long-term outcome of stent placement in the management of acute malignant
      colorectal obstruction. METHODS: From July 2002 to April 2005, 29 self-expanding
      metal stents were placed in 24 patients (13 men, mean age 67 years, range 36-83).
      Stents were inserted under endoscopic and fluoroscopic control. Patients were
      clinically and endoscopically followed up. RESULTS: Twenty-eight out of 29 stents
      were successfully placed (96.5%) in 23 out of 24 patients with 25 strictures. The
      clinical success rate was 95.8% (23/24). Two early stent migrations were observed
      in two patients (8.3%). Late complications developed in eight patients (33.3%)
      after a median of 3.8 months (range <1-8.6): two migrations and six occlusions.
      The median survival was 9.8 months (range <1-27). Eleven patients (45.8%) died
      from progressive disease without any clinical evidence of recurrent obstruction.
      CONCLUSION: Stent placement is safe and effective. Stent complications are
      frequent but not life-threatening, and are easy to manage. An improvement in
      stent design and well-scheduled follow-up are needed in order to prevent such
      complications.

PMID- 16574516
TI  - PSOAS abscess: an atypical initial presentation of Crohn's disease.

PMID- 16574517
TI  - Chromoendoscopy in Barrett's oesophagus: is cresyl violet the magic bullet?

PMID- 16574518
TI  - Gastro-oesophageal reflux disease and lactose malabsorption: Casual comorbidity
      or neglected association?

PMID- 16574521
TI  - Fever without source in children 0 to 36 months of age.
AB  - Although fever in the young child (0-36 months) is a common clinical problem, the
      evaluation and treatment of febrile children remain controversial. Furthermore,
      universal vaccination with the heptavalent pneumococcal conjugate vaccine (PCV7)
      has changed the epidemiology of invasive bacterial disease in young children.
      This article addresses the approach to febrile neonates (0-28 days old), young
      infants (1-3 months old), and older infants and toddlers (3-36 months old) in the
      PCV7 era.

PMID- 16574519
TI  - High prevalence of asymptomatic vertebral fractures in post-menopausal women
      receiving chronic glucocorticoid therapy: a cross-sectional outpatient study.
AB  - Glucocorticoid (GC)-induced osteoporosis mostly affects trabecular bone of
      vertebrae. Only 30% of vertebral fractures are symptomatic, yet both clinical and
      radiological vertebral fractures have been associated with increased mortality
      and morbidity. The aims of this cross-sectional, outpatient-based study were to
      measure the prevalence of asymptomatic vertebral fractures in a large sample of
      post-menopausal women given GCs for different diseases; to compare prevalence of
      asymptomatic vertebral fractures according to disease, GC treatment and major
      risk factors; and to assess the quality of life in GC users with and without
      asymptomatic vertebral fractures. 551 patients referring to 39 centers as
      outpatients for their programmed follow-up and satisfying the inclusion criteria
      were included in the analysis. Each patient underwent structured medical
      interview (including dose and duration of GC therapy, major risk factors for
      osteoporosis, the quality of life questionnaire of the European Foundation for
      Osteoporosis (QUALEFFO) and a back function score questionnaire), thoraco-lumbar
      radiographs and subsequent morphometry; for 253 and 437 patients, respectively,
      lumbar spine bone mineral density (BMD) assessed by dual energy X-ray
      absorptiometry and calcaneal bone stiffness assessed by quantitative
      ultrasonometry were available. The prevalence of asymptomatic vertebral fractures
      resulted >37%, with >14% of patients having two or more asymptomatic vertebral
      fractures and was much higher than that found in epidemiological studies on
      healthy women. Distribution of asymptomatic vertebral fractures along the spine
      showed a bimodal pattern, with two peaks at T7 and T11. The prevalence of
      asymptomatic vertebral fractures clearly increased with age. Differences in
      prevalence among diseases were evidenced. When controlled for age, GC cumulative
      dose, duration of therapy and personal history of fractures, the adjusted
      prevalences were 30.77% for systemic lupus erythematosus, 33.78% for rheumatoid
      arthritis, 37.78% for asthma/chronic obstructive pulmonary disease, 43.20% for
      polymyalgia rheumatica and 43.36% for diseases grouped as "other
      vasculitides/connective tissue diseases". No significant association was found
      with GC cumulative dose and duration of therapy. Established risk factors for
      osteoporosis (except for age, years since menopause and personal history of
      fractures), lumbar spine BMD, calcaneal stiffness and QUALEFFO score were not
      associated with number and severity of asymptomatic vertebral fractures.
      Underlying disease is likely to contribute to the risk of fracture, but disease
      by itself could not be dissected from GC regimen. Vertebral fractures should be
      looked for carefully in all post-menopausal women receiving long-term systemic
      GCs since they can be asymptomatic and are scarcely predictable.

PMID- 16574523
TI  - Airway infectious disease emergencies.
AB  - Upper and lower respiratory infections are encountered commonly in the emergency
      department. Visits resulting from occurrences of respiratory disease account for
      10% of all pediatric emergency department visits and 20% of all pediatric
      hospital admissions. Causes of upper airway infections include croup,
      epiglottitis, retropharyngeal abscess, cellulitis, pharyngitis, and peritonsillar
      abscesses. Lower airway viral and bacterial infections cause illnesses such as
      pneumonia and bronchiolitis. Signs and symptoms of upper and lower airway
      infections overlap, but the differentiation is important for appropriate
      treatment of these conditions. This article reviews the varied clinical
      characteristics of upper and lower airway infections.

PMID- 16574522
TI  - Pediatric ear, nose, and throat emergencies.
AB  - Acute otitis media is the most common infection for which antibiotics are
      prescribed in children, resulting in more than 20 million antibiotic
      prescriptions annually. New practice guidelines published by the American Academy
      of Pediatrics and the American Academy of Family Physicians call for the
      judicious use of antibiotics in view of increasing antibiotic resistance and the
      unclear necessity of the use of antibiotics in children with uncomplicated acute
      otitis media. This article reviews those guidelines, several other common ear,
      nose, and throat entities, including sinusitis and dental emergencies, and
      current strategies in diagnosis and treatment.

PMID- 16574524
TI  - Pediatric blunt abdominal trauma.
AB  - Blunt pediatric trauma is a major threat to the health and well-being of
      children. Nationwide, many practitioners care for children who face this issue.
      Some key principles related to the evaluation and management of these children
      are elucidated in this article.

PMID- 16574525
TI  - Seizures in children.
AB  - Seizures are the most common pediatric neurologic disorder. Four to ten percent
      of children suffer at least one seizure in the first 16 years of life. The
      incidence is highest in children less than 3 years of age, with a decreasing
      frequency in older children. Epidemiologic studies reveal that approximately
      150,000 children will sustain a first-time unprovoked seizure each year, and of
      those, 30,000 will develop epilepsy. This article describes the types, diagnoses,
      and management and disposition of this pediatric neurologic disorder.

PMID- 16574526
TI  - Pediatric procedural sedation and analgesia.
AB  - Children often present with painful conditions that require painful
      interventions. Procedural sedation and analgesia refers to the pharmacologic
      technique of managing a child's pain and anxiety. Procedural sedation is a safe,
      effective, and humane way to facilitate appropriate medical care. It is important
      to distinguish the goals for the procedural sedation, pain relief or anxiolysis
      or both. Different medications and combinations of medications can be used to
      achieve the desired effect. It is also important to keep in mind the possible
      adverse reactions and side effects associated with each medication when choosing
      the sedation cocktail.

PMID- 16574527
TI  - Deadly ingestions.
AB  - More than 50% of the toxic-exposure calls to US poison centers involve children.
      Although most of these exposures are nontoxic, there are several products and
      medications that are widely available to the pediatric population that can lead
      to severe toxicity or even death. With some of these medications, death or severe
      symptoms can occur with the ingestion of only a small amount. It is important
      that the clinician be familiar with presenting signs and symptoms of potentially
      toxic ingestions and is able to initiate a therapeutic and life-saving
      intervention. This article reviews some of the deadlier ingestions that children
      may be exposed to.

PMID- 16574528
TI  - QT interval prolongation associated with venlafaxine administration.
AB  - A significant number of non-antiarrhythmic drugs including psychotropic agents
      have been shown to prolong cardiac repolarization increasing the risk for torsade
      de pointes ventricular tachycardia. We briefly describe a 60-year-old woman who
      admitted to the hospital due to hypertension and mild dyspnea having a prolonged
      QT interval (QTc: 582 ms). The patient had a known history of depression treated
      with venlafaxine. The QT interval normalised a few days after cessation of the
      antidepressant agent. This is the first report of venlafaxine-induced QT interval
      prolongation.

PMID- 16574530
TI  - Ischemic stroke mimicking acute myocardial infarction, a diagnostic dilemma.
AB  - Neurocardiogenic dysfunction is described in acute neurological injury. We report
      a case of ischemic stroke mimicking acute myocardial infarction.

PMID- 16574529
TI  - MDCT of the anomalous origin of the right coronary artery from the left sinus of
      Valsalva as a single coronary artery.

PMID- 16574531
TI  - Mitral A-wave deceleration time. A marker of left ventricular diastolic
      dysfunction following acute myocardial infarction?

PMID- 16574532
TI  - Diagnostic and economic impact of heart failure induced mediastinal
      lymphadenopathy.

PMID- 16574533
TI  - Predictive factors of a fulminant course in acute myocarditis.
AB  - BACKGROUND: Patients who develop fulminant myocarditis often die of sudden
      cardiac arrest, arrhythmia, or severe heart failure soon after onset if they do
      not receive percutaneous cardiopulmonary support in time. The purpose of this
      study was to identify the risk factors of clinical symptoms/signs or laboratory
      findings that could predict the fulminant course of acute myocarditis. METHODS
      AND RESULTS: Thirty-five patients (mean age 28 +/- 8 years, 17 males) who had
      been admitted to intensive care unit with the diagnosis of acute myocarditis by
      clinical presentations were retrospectively recruited. They were divided into the
      fulminant group (n = 11) and the non-fulminant group (n = 24). Clinical features,
      laboratory data, and images on admission were analyzed. Overall in-hospital
      mortality was 17% (6/35). Mortality was higher in the fulminant group (45% vs.
      4%, p = 0.027). Multivariate analysis revealed that prolongations of the QRS
      complex (118 +/- 27 vs. 88 +/- 10 ms, p = 0.048) and depressed left ventricular
      ejection fraction (41 +/- 7% vs. 57 +/- 7%, p = 0.027) were the only independent
      factors significantly associated with the fulminant course of acute myocarditis.
      CONCLUSION: The in-hospital mortality of acute fulminant myocarditis was high.
      Prolongations of the QRS complex and depressed left ventricular ejection fraction
      on admission were independent positive predictors for the development of acute
      fulminant myocarditis.

PMID- 16574534
TI  - [Thrombophilic factors in divers with undeserved decompression sickness].
AB  - In divers with a vascular disease in decompression sickness, who have not
      committed any technical error, thrombophilic risk factors were sought. Six cases
      of confirmed divers, without diving technical error, were investigated.
      Thrombophilic screening included proteins C, S, antithrombin III, and factor VIII
      assays, and circulating antibodies, Factor V Leiden, and mutation G20210A
      mutation in Factor II gene research. Total plasma homocysteine (Hcy), an
      atherosclerosis factor, even when slightly increased, nutitional factors: folate
      and vitamins B12 and B6, the cofactors of its metabolism, and inversely
      correlated with Hcy values, were assayed, and subjects were genotyped for
      mutation C677T in the MTHFR gene. RESULTS: In five divers, Hcy values were
      moderately increased, and in all the six, folate and/or B12 values were
      decreased. Three of them showed a genotype TT (mutation C677T), two, the genotype
      CT, and the sixth, an heterozygous Factor V Leiden. In these divers, a
      predisposition for vascular diseases, was detected, which was partially curable.

PMID- 16574535
TI  - The challenge of acute rheumatic fever diagnosis in a high-incidence population:
      a prospective study and proposed guidelines for diagnosis in Australia's Northern
      Territory.
AB  - BACKGROUND: Accurate diagnosis of acute rheumatic fever (ARF) remains problematic
      in high-incidence settings and especially in the Aboriginal population of
      Australia's Northern Territory. Previous investigators have demonstrated that
      strict application of the 1992 Updated Jones Criteria results in under-diagnosis.
      This study's objectives were to review use of the Jones Criteria (1992 Update) in
      diagnosing ARF in Australian Aboriginal patients presenting with suspected
      rheumatic fever, and formulate a locally relevant algorithm to improve diagnosis.
      METHODS: Patients presenting to Royal Darwin Hospital with suspected ARF were
      prospectively assessed during a 15-month period. Demographic information,
      clinical history, examination, laboratory and echocardiographic findings were
      documented in order to determine whether the Jones Criteria were fulfilled, and
      to identify alternative diagnoses. The hospital discharge diagnosis was recorded
      and patients were followed up 18-33 months later. RESULTS: Out of 35 patients
      with suspected ARF, all were Aboriginal Australians, 17 (49%) had a discharge
      diagnosis of definite ARF, 7 (20%) had definite non-rheumatic fever diagnoses
      (disseminated gonococcal infection, systemic lupus erythematosis, buttock abscess
      and other febrile illnesses in children with cardiac murmur due to previously
      undiagnosed RHD). The remaining 11 (31%) posed diagnostic difficulties because of
      mild symptoms that failed to fulfil Jones Criteria (attracting diagnoses such as
      'unexplained arthralgia') or atypical features such as older age. Two patients
      whose illness initially failed to fulfil the Jones Criteria, who were neither
      diagnosed with ARF nor commenced on secondary benzathine penicillin prophylaxis,
      were found on follow-up to have definite and probable ARF, respectively. At least
      29% (8/28) of patients without prior recognised ARF/RHD had echocardiographic
      evidence of established RHD, indicating that previous episodes were missed.
      CONCLUSIONS: Individual mild episodes of ARF may be overlooked, with patients
      missing out on the timely institution of secondary prophylaxis. The Jones
      Criteria should be supplemented by active exclusion of differential diagnoses and
      vigilant follow-up including echocardiography. 'Probable' and 'possible ARF'
      should be recognised as diagnostic categories applying to patients not fulfilling
      the Jones Criteria but who nevertheless should be offered prophylactic penicillin
      at least until further follow-up. A set of diagnostic guidelines is proposed.

PMID- 16574536
TI  - Coronary bypass surgery for patients with chronic poor preoperative left
      ventricular function (EF<30%): 5-year follow-up.
AB  - BACKGROUND: Optimal therapy for patients with coronary artery disease and chronic
      poor left ventricular function, given the absence of randomized trials, is
      unclear. Although coronary surgery has been performed in such patients for 25
      years, it is perceived as high risk and unproven long-term benefit, especially if
      thallium scanning fails to demonstrate large areas of viability. We report the
      results of coronary surgery in these patients. METHODS: Retrospective analysis by
      a standardized patient questionnaire, of 107 such consecutive patients offered
      coronary surgery. RESULTS: Mean follow-up was 3.3 years (range, 0.5-5.5); average
      patient age was 64.4+/-1 years. Preoperative thallium scans were performed solely
      on 31 patients with none or mild angina, of which 10 (32%) demonstrated large
      areas of viable myocardium. Perioperative mortality was 1.9%. On multivariate
      analysis, factors predictive of increased perioperative death were recent
      myocardial infarction (p<0.001) and nonelective surgery (p<0.001). Kaplan-Meier 5
      year survival and freedom from major adverse cardiac events were 72.3 and 82.3%,
      respectively. In 21 patients, with preoperative nil-to-mild angina and nil-to
      small areas of myocardial viability, thallium scanning failed to predict a
      successful outcome. CONCLUSION: Offering coronary surgery to these patients
      irrespective of thallium testing is safe and effective in the medium term. Early
      surgery is recommended.

PMID- 16574537
TI  - Sildenafil as adjunct therapy to high-dose epoprostenol in a patient with
      pulmonary veno-occlusive disease.
AB  - Pulmonary veno-occlusive disease is refractory to medical treatment and is
      generally associated with a poor prognosis. Treatment with vasodilators, such as
      prostacyclin, of patients with PVOD is controversial because of concerns
      regarding hemodynamic deterioration. Although a preferential pulmonary
      vasodilatory effect of a specific phosphodiesterase-5 inhibitor, sildenafil, has
      recently been reported in patients with primary pulmonary hypertension, little
      information is available regarding the effect of sildenafil on patients with
      pulmonary veno-occlusive disease. In the present case, remarkable improvement of
      hemodynamics and of clinical course was produced by adjunctive use of oral
      sildenafil in association with intravenous high-dose epoprostenol. These findings
      suggest that sildenafil may be a therapeutic option in the medical treatment of
      pulmonary veno-occlusive disease.

PMID- 16574538
TI  - Mitral valve replacement in a severely calcified posterior annulus: a novel
      technique.
AB  - We describe a technique for insertion of a mitral valve prosthesis in the
      presence of severe posterior annular calcification by plicating the left atrial
      tissue over the sewing ring. Extensive calcification often creates the technical
      difficulty of seating the prosthetic valve resulting in peri prosthetic leakage.
      Extensive decalcification may weaken the annulus and result in prosthetic valve
      dehiscence and atrioventricular dissociation.

PMID- 16574540
TI  - Trading places.

PMID- 16574539
TI  - Intraaortic balloon pump insertion through the subclavian artery. Subclavian
      artery insertion of IABP.
AB  - The intraaortic balloon pump (IABP) is frequently used in the management of
      cardiac failure in the setting of myocardial infarction or as a bridge for
      coronary revascularisation surgery. The IABP is usually inserted through the
      femoral artery. Occasionally severe aorto-iliac occlusive disease prevents the
      retrograde passage of the balloon, in which case an anterograde route, usually
      through the ascending aorta is used. We describe four patients in whom an IABP
      was placed through the subclavian artery by the joint efforts of cardiologists
      and vascular surgeons.

PMID- 16574541
TI  - Keynote comment: inequalities and shortcomings in European cancer care.

PMID- 16574542
TI  - Selective serotonin-reuptake inhibitors and chemoprevention of colorectal cancer.

PMID- 16574543
TI  - D3 or not D3... that is not the question.

PMID- 16574545
TI  - Use of antidepressants and risk of colorectal cancer: a nested case-control
      study.
AB  - BACKGROUND: Animal studies suggest that selective serotonin reuptake inhibitors
      (SSRI) retard the growth of colorectal tumours, whereas tricyclic antidepressants
      increase the risk of colorectal cancer. We aimed to assess whether SSRI use was
      associated with a decreased risk of colorectal cancer, and tricyclic
      antidepressant use with an increased risk of colorectal cancer. METHODS: We did a
      population-based nested case-control study from Jan 1, 1981, to Dec 31, 2000, of
      people aged 5-85 years who were registered with Saskatchewan Health and eligible
      for prescription-drug benefit. Between Jan 1, 1981, and Dec 31, 2000, 6544 cases
      with colorectal cancer were identified from the Saskatchewan Cancer Agency
      registry and analysed for use of tricyclic antidepressants; between Jan 1, 1991,
      and Dec 31, 2000, 3367 cases with colorectal cancer were identified from the
      Saskatchewan Cancer Agency registry and analysed for SSRI use. For every case,
      four eligible controls matched for age, sex, and calendar time (ie, free of any
      cancer in calendar month of case diagnosis) were selected randomly by a
      statistician who used incidence density sampling. By use of conditional logistic
      regression, we assessed incidence-rate ratios of having colorectal cancer in
      association with use of antidepressants, analysing dose and time of use.
      FINDINGS: A decreased risk of colorectal cancer was associated with high (ie,
      >6.0x10(-6) mol per day) daily SSRI dose during 0-5 years before diagnosis
      (incidence-rate ratio 0.70 [95% CI 0.50-0.96], p for trend=0.0172), adjusted for
      age, sex, use of non-steroidal anti-inflammatory drugs in the same period, and
      SSRI use during 6-10 years before index date (ie, date of diagnosis for a case
      and the same date for matched controls). No consistent relation was recorded for
      risk of colorectal cancer and use of tricyclic antidepressants. INTERPRETATION:
      SSRI use might inhibit the growth of colorectal tumours through an antipromoter
      effect or direct cytotoxic effect. Further investigation is needed, with more
      complete assessment of confounders such as lifestyle factors (eg, diet), use of
      drugs, and comorbidity (eg, diabetes or inflammatory bowel disease) that might
      affect the occurrence of colorectal cancer.

PMID- 16574546
TI  - Nodal dissection for patients with gastric cancer: a randomised controlled trial.
AB  - BACKGROUND: The survival benefit and morbidity after nodal dissection for gastric
      cancer remains controversial. We aimed to do a single-institution randomised
      trial to compare D1 (ie, level 1) lymphadenectomy with that of D3 (ie, levels 1,
      2, and 3) dissection for gastric cancer in terms of overall survival and disease
      free survival. METHODS: From Oct 7, 1993, to Aug 12, 1999, 335 patients were
      registered. 221 patients were eligible, 110 of whom were randomly assigned D1
      surgery and 111 of whom were randomly assigned D3 surgery, both with curative
      intent. Three participating surgeons had done at least 25 independent D3
      dissections before the start of the trial, and every procedure was verified by
      pathological analyses. The primary endpoints were 5-year overall survival and 5
      year disease-free survival. We also analysed risk of recurrence. Main analyses
      were done by intention to treat. This trial is registered at the US National
      Institute of Health website . FINDINGS: Median follow-up for the 110 (50%)
      survivors was 94.5 months (range 62.9-135.1). Overall 5-year survival was
      significantly higher in patients assigned D3 surgery than in those assigned D1
      surgery (59.5% [95% CI 50.3-68.7] vs 53.6% [44.2-63.0]; difference beteween
      groups 5.9% [-7.3 to 19.1], log-rank p=0.041). 215 patients who had R0 resection
      (ie, no microscopic evidence of residual disease) had recurrence at 5 years of
      50.6% [41.1-60.2] for D1 surgery and 40.3% [30.9-49.7] for D3 surgery (difference
      between groups 10.3% [-3.2 to 23.7], log-rank p=0.197). INTERPRETATION: D3 nodal
      dissection, compared with that of D1, offers a survival benefit for patients with
      gastric cancer when done by well trained, experienced surgeons.

PMID- 16574547
TI  - Advances in oral therapy for multiple myeloma.
AB  - Conventional intravenous chemotherapy regimens are toxic, cumbersome, and
      negatively affect patients' quality of life, with oral treatment preferable to
      most patients with cancer. Multiple myeloma is the second most common
      haematological malignant disease, but cannot be cured with conventional and high
      dose chemotherapy. New oral treatments that target myeloma cells or bone marrow
      are being developed that are highly effective yet have low toxic effects, such as
      the immunomodulatory drugs thalidomide and lenalidomide. Several treatments in
      early development have shown antimyeloma activity, including: CHIR-258, which
      inhibits fibroblast growth factor receptor 3; NVP-ADW742, which inhibits insulin
      like growth factor receptor 1; and PTK787, which inhibits vascular endothelial
      growth factor. Additional drugs aimed at switching off silenced genes include
      histone deacetylase inhibitors. The availability of these various oral treatments
      is hoped to improve regimens that, if used sequentially or in combination, offer
      the potential of making multiple myeloma a chronic disease, thereby extending
      patients' lifespans and improving quality of life.

PMID- 16574548
TI  - Radiation-related damage to dentition.
AB  - Because of typical tissue reactions to ionising radiation, radiotherapy in the
      head and neck region usually results in complex oral complications affecting the
      salivary glands, oral mucosa, bone, masticatory musculature, and dentition. When
      the oral cavity and salivary glands are exposed to high doses of radiation,
      clinical consequences including hyposalivation, mucositis, taste loss, trismus,
      and osteoradionecrosis should be regarded as the most common side-effects.
      Mucositis and taste loss are reversible consequences, usually subsiding early
      post-irradiation, whereas hyposalivation is commonly irreversible. Additionally,
      the risk of rampant tooth decay with its sudden onset and osteonecrosis is a
      lifelong threat. Thus, early, active participation of the dental profession in
      the development of preventive and therapeutic strategies, and in the education
      and rehabilitation of patients is paramount in consideration of quality-of-life
      issues during and after radiotherapy. This Review focuses on the multifactorial
      causes of so-called radiation caries and presents possible treatment strategies
      to avoid loss of dentition.

PMID- 16574549
TI  - The Calman-Hine report: a personal retrospective on the UK's first comprehensive
      policy on cancer services.
AB  - Calman-Hine was the first comprehensive cancer report to be produced in the UK,
      and set out principles for cancer care and the clinical organisation for service
      delivery. It advocated a change from a generalist model (eg, care given by
      general surgeons and physicians) that was supported by specialists to a fully
      specialist service. The process of policy development was innovative and the
      report was accepted widely throughout the UK. However, implementation, which
      began at a time of organisational change across the UK National Health Service
      (NHS), was not addressed sufficiently in the years immediately after publication.
      Consequently, change was more variable both geographically and within a single
      location and took longer than necessary. Evidence from research, routine data,
      and external assessments suggest that the policy was eventually successful and a
      worthwhile change. Well thought out and sustained mechanisms for policy
      implementation are as crucial as well-designed policies, and government health
      reforms can conflict with specific policies for quality improvement.

PMID- 16574550
TI  - Controversies surrounding body mass, reflux, and risk of oesophageal
      adenocarcinoma.
AB  - At first the association between body mass, reflux, and oesophageal
      adenocarcinoma might seem easily interpreted, but a more thorough assessment of
      the published work shows that several factors are missing. Reflux and obesity are
      established risk factors for oesophageal adenocarcinoma, particularly when they
      occur in combination. However, the interplay between these and other factors with
      regard to oesophageal adenocarcinoma is uncertain. Moreover, the contribution of
      these risk factors in explaining the increasing incidence of oesophageal
      adenocarcinoma is unclear, because the trends in prevalence of reflux and obesity
      do not match those of incidence of oesophageal adenocarcinoma. Moreover, none of
      these factors contribute strongly to the striking predominance of oesophageal
      adenocarcinoma in men. Thus, several factors that can explain the development of
      oesophageal adenocarcinoma need to be addressed.

PMID- 16574551
TI  - Cytoplasmic nucleophosmin in myeloid sarcoma occurring 20 years after diagnosis
      of acute myeloid leukaemia.

PMID- 16574552
TI  - Severe rhabdomyolysis associated with pemetrexed-based chemotherapy.

PMID- 16574553
TI  - Breast-cancer metastasis in the round ligament of the liver.

PMID- 16574554
TI  - Autoantibodies to intracellular autoantigens and their B-cell epitopes: molecular
      probes to study the autoimmune response.
AB  - A common laboratory finding in systemic autoimmune diseases is the presence of
      autoantibodies against intracellular autoantigens. Although their pathogenesis is
      not fully understood, autoantibodies are important tools for establishing
      diagnosis, classification, and prognosis of autoimmune diseases. Autoantibodies
      mainly target multicomponent complexes containing both protein antigens and
      (ribo)-nucleic acid(s), such as the spliceosome or Ro/La RNPs. In this review, we
      address the main characteristics and the clinical value of the main autoantibody
      types with respect to their disease association, and we describe the
      corresponding autoantigens, their biologic function, and their B-cell antigenic
      determinants (epitopes). The structural characteristics and clinical associations
      of these epitopes, and their utility as tools to investigate the autoimmune
      response, are discussed in detail. New insights into the pathogenetic role of
      epitopes in systemic autoimmunity are also examined. In this regard, using the
      defined structures of the B-cell antigenic epitopes, complementary epitopes can
      be designed according to the "molecular recognition" theory. These complementary
      epitopes can be used as probes to study pathogenetic and immunoregulatory aspects
      of the anti-idiotypic response. The origin of humoral autoimmunity and the
      spreading of the epitopes in systemic lupus erythematosus are also discussed.
      Finally, the ability of post-translational modifications to induce autoreactive
      immune attack via the generation of neo-epitopes is summarized.

PMID- 16574555
TI  - Inherited thrombophilia.
AB  - Inherited thrombophilia can be defined as a genetically determined predisposition
      to the development of thromboembolic complications. Since the discovery of
      activated protein C resistance in 1993, several additional disorders have been
      described and, at present, it is possible to identify an inherited predisposition
      in about 60 to 70% of patients with such complications. These inherited
      prothrombotic risk factors include qualitative or quantitative defects of
      coagulation factor inhibitors, increased levels or function of coagulation
      factors, defects of the fibrinolytic system, altered platelet function, and
      hyperhomocysteinemia. In this review, the main inherited prothrombotic risk
      factors are analyzed from epidemiological, laboratory, clinical, and therapeutic
      points of view. Finally, we discuss the synergism between genetic and acquired
      prothrombotic risk factors in particular conditions such as childhood and
      pregnancy.

PMID- 16574556
TI  - The future of British surgery.

PMID- 16574557
TI  - Some patients with multiple sclerosis have neurovascular compression causing
      their trigeminal neuralgia and can be treated effectively with MVD: report of
      five cases.
AB  - The role of trigeminal ganglion percutaneous injection and radio-frequency
      lesioning procedures for the treatment of trigeminal neuralgia (TGN) in multiple
      sclerosis (MS) is well established. There is general acceptance that
      microvascular decompression (MVD) cannot be an appropriate treatment due to the
      view that the underlying aetiology is a demyelinating plaque affecting the root
      entry zone of the trigeminal pathway. Recently, MR-imaging has been used in the
      preoperative investigation of this group of patients demonstrating that
      neurovascular compression can occasionally be the responsible mechanism and that
      MVD can be the treatment of choice. We present five cases with MS and TGN. All
      the patients had failed to respond to medical treatment or percutaneous
      procedures. Magnetic resonance imaging demonstrated evidence of neurovascular
      compression in four cases. All the patients underwent MVD. Postoperatively four
      of the five patients made an uncomplicated recovery, were pain-free and fully
      satisfied with the result (mean follow-up 38.75 months; range 8-59 months). One
      patient developed recurrent pain 1 week following surgery and went on to have a
      total sensory rhizotomy. TGN in MS can be caused by neurovascular compression,
      which may be identified on MR-imaging. MVD has offered satisfactory short-term
      outcome for at least 2 years and does not inflict sensory loss. Longer follow-up
      will determine whether the outcome in MS patients will be as successful as in the
      TGN patients who do not suffer from MS.

PMID- 16574558
TI  - Loss of inter-vertebral disc height after anterior cervical discectomy.
AB  - Most surgeons undertaking anterior cervical discectomy (ACD) introduce a bone
      graft or cage into the disc space when the decompression is complete. This is
      done to prevent segmental collapse, preserve cervical spine alignment and to
      promote fusion. We have conducted a prospective observational cohort study to
      investigate the relationship between loss of disc height, cervical spine
      alignment and clinical outcome in 140 patients undergoing ACD without inter-body
      graft or cage. At a minimum of 12 months after operation changes in disc space
      height and cervical spine alignment were correlated with clinical outcome
      measured by SF36, Neck Disability Index, and visual analogue neck and arm pain
      scores. There was no relationship between loss of disc height and outcome. Loss
      of the overall cervical lordosis was present in 71 patients and segmental
      kyphosis was found in 69. Analysis of clinical outcome showed no significant
      differences between patients with preserved and abnormal cervical alignment.
      Neither loss of disc height nor disturbance of cervical alignment compromised
      clinical outcome in the first year following ACD.

PMID- 16574559
TI  - Preoperative spinal hydrodynamics versus clinical change 1 year after shunt
      treatment in idiopathic normal pressure hydrocephalus patients.
AB  - Nineteen consecutive cases treated for idiopathic normal pressure hydrocephalus
      (iNPH) with ventriculo-peritoneal shunts were clinically followed prospectively.
      Change in clinical state one year after shunt surgery was assessed as change on a
      15-3 score NPH Grade Scale. Preoperative spinal hydrodynamics were assessed using
      a constant-rate lumbar infusion test. The pressure recordings were stored as raw
      data files and analysed retrospectively with regard to the mean cerebrospinal
      fluid pressure (CSFP), as well as mean CSFP wave amplitudes. Changes in NPH score
      1 year after shunt surgery correlated significantly with the levels of single
      CSFP wave amplitudes, but not with the lumbar resistance to CSF outflow (R(out)).
      Mean CSFP wave amplitude was thus, in this cohort, a better predictor of clinical
      change one year after shunt treatment than R(out).

PMID- 16574560
TI  - Frameless stereotactic placement of ventriculoperitoneal shunts in undersized
      ventricles: a simple modification to free-hand procedures.
AB  - The aim of this report is to introduce a simple modification to the free-hand
      frameless stereotactic placement of ventriculoperitoneal shunts in undersized
      ventricles. In this technical note, we describe our experience with ventricular
      catheter placement in two children suffering from shunt dependent idiopathic
      intracranial hypertension using an image-guided instrument holder with a catheter
      guide. In both patients, the surgical procedure proved to be easy and accurate,
      with good initial clinical results. The use of an image-guided instrument holder
      is a modification to the free-hand frameless stereotactic placement of
      ventriculoperitoneal shunts in undersized ventricles.

PMID- 16574561
TI  - Preoperative cervical traction in cases of cranial settling with halo ring and
      Mayfield skull clamp.
AB  - Rheumatoid cervical myelopathy presents one of the most daunting challenges in
      neurological surgery. Preoperative cervical traction can help to distract the
      dens from the brainstem prior to performing occipitocervical fusion in cases of
      cranial settling. Valuable millimetres gained in preoperative traction can be
      lost in placing the patient in the prone position after removing the halo to
      allow application of the Mayfield skull clamp. The authors have found that
      traction can be adequately maintained during surgery by applying the Mayfield
      skull clamp with skull pins to the halo ring itself.

PMID- 16574562
TI  - Decompressive surgery for acute subdural haematoma leading to contralateral
      extradural haematoma: a report of two cases and review of literature.
AB  - Development of a contralateral epidural haematoma during or immediately after
      cranial surgery is a well-described entity. However, in a case of acute subdural
      haematoma where the brain is usually tense, postoperative development of
      contralateral extradural haematoma is uncommon. We report two cases of
      contralateral extradural haematoma after decompressive surgery for acute subdural
      haematoma. We recommend routine postoperative CT immediately after cranial
      surgery for head trauma. This would help in timely detection and treatment of
      such a complication.

PMID- 16574564
TI  - Persistent and intractable ventriculitis due to retained ventricular catheters.
AB  - It is generally recommended that, in cases of difficulty in removing a
      ventricular catheter during a shunt revision, it is best left alone to avoid
      intraventricular haemorrhage. Retained ventricular catheters (RVCs) are usually
      safe, although in the presence of ventriculitis they may become colonized by
      organisms and become a source of persistent or recurrent infection. The authors
      present a case of persistent and intractable ventriculitis due to an old retained
      ventricular catheter. A 23-year-old female, who had a RVC and a functioning
      shunt, was admitted for a suspected blocked shunt. At surgery the shunt was found
      to be infected and external drainage was instituted. Over the next 4 months, she
      developed intractable and persistent staphylococcal ventriculitis, despite
      undergoing 10 further surgical procedures, and appropriate intravenous and
      intrathecal antibiotic therapy. She responded rapidly only after surgical removal
      of the old RVC via a craniotomy. The staphylococcus cultured from the RVC had an
      identical antibiogram to the organism responsible for the intractable
      ventriculitis. This case emphasizes the point that, although RVC are generally
      considered safe, removal becomes imperative in the presence of concurrent CSF
      infection that fails to respond quickly to intrathecal antibiotic therapy.

PMID- 16574563
TI  - Severe fibrous dysplasia of the craniovertebral junction with transient
      quadriparesis: a complicated case.

PMID- 16574565
TI  - A case of raised intracranial pressure due to multiple lumbar nerve root
      melanotic schwannomas.
AB  - We report a patient with multiple cranial nerve and lumbar spine nerve root
      melanotic schwannomas, a rare variant of schwannoma, with raised intracranial
      pressure. Possible pathophysiology of the raised intracranial pressure by
      decreased CSF resorption due to blocked spinal lymphatics and other mechanisms is
      discussed.

PMID- 16574566
TI  - Malignant transformation of posterior fossa epidermoid cyst.
AB  - The authors report the case of a 45-year-old man who presented with a short
      duration of a painful ophthalmoparesis. Initial magnetic resonance imaging
      revealed an extraaxial petroclival mass characteristic of an epidermoid cyst,
      with the exception of a contiguous contrast-enhancing lobule. A subtotal
      resection was performed with the histopathological diagnosis revealing malignant
      transformation of an epidermoid cyst. Despite aggressive postoperative adjuvant
      therapy, the patient developed leptomeningeal metastasis and died shortly
      thereafter. The presence of contrast enhancement at the site of an epidermoid
      cyst combined with an acute, progressive neurological deficit should alert the
      treating physician to the possibility of a malignant transformation. When
      transformation does occur, the clinical and radiological course is quite
      aggressive as compared with the indolent growth of epidermoid cysts. Treatment
      options include surgery with adjuvant chemotherapy or radiotherapy. We review the
      pertinent features of this case along with the relevant literature regarding
      primary intracranial squamous cell carcinomas.

PMID- 16574567
TI  - Haemorrhage into the ligamentum flavum of the lumbar spine: case report and
      review of the literature.

PMID- 16574577
TI  - Visualization in the neurosciences: seeing abstractions in real time.
AB  - One explicit goal of visualization in the neurosciences is to present data to
      human observers in a way that is informative and meaningful, on the one hand, yet
      intuitive and effortless on the other. Multidimensional data visualization is
      concerned with the question "How can we display high-dimensional data elements in
      a low-dimensional environment, such as on a computer screen or the printed page?"
      This goal is often pursued by attaching "features" such as hue, intensity,
      spatial location, and size to each data element. Features are chosen to reveal
      properties of data elements as well as relationships among them. An ad hoc
      assignment of features to individual data dimensions may not result in a useful
      visualization tool. Indeed, too often the tool itself interferes with the
      viewer's ability to extract the desired information due to a poor choice of
      feature assignment. The articles presented in this issue address the concerns of
      representing data to better elucidate complex concepts in the neurosciences.

PMID- 16574578
TI  - Typology of nonlinear activity waves in a layered neural continuum.
AB  - Neural tissue, a medium containing electro-chemical energy, can amplify small
      increments in cellular activity. The growing disturbance, measured as the
      fraction of active cells, manifests as propagating waves. In a layered geometry
      with a time delay in synaptic signals between the layers, the delay is
      instrumental in determining the amplified wavelengths. The growth of the waves is
      limited by the finite number of neural cells in a given region of the continuum.
      As wave growth saturates, the resulting activity patterns in space and time show
      a variety of forms, ranging from regular monochromatic waves to highly irregular
      mixtures of different spatial frequencies. The type of wave configuration is
      determined by a number of parameters, including alertness and synaptic
      conditioning as well as delay. For all cases studied, using numerical solution of
      the nonlinear Wilson-Cowan (1973) equations, there is an interval in delay in
      which the wave mixing occurs. As delay increases through this interval, during a
      series of consecutive waves propagating through a continuum region, the activity
      within that region changes from a single-frequency to a multiple-frequency
      pattern and back again. The diverse spatio-temporal patterns give a more concrete
      form to several metaphors advanced over the years to attempt an explanation of
      cognitive phenomena: Activity waves embody the "holographic memory" (Pribram,
      1991); wave mixing provides a plausible cause of the competition called "neural
      Darwinism" (Edelman, 1988); finally the consecutive generation of growing neural
      waves can explain the discontinuousness of "psychological time" (Stroud, 1955).

PMID- 16574579
TI  - Statistical analysis of morphological differences between brains.
AB  - Recent study in neuroscience has observed evidence that the anatomic structures
      in human brains might have certain connection with the functioning. This triggers
      the interest in morphological study of cortical surfaces and in comparison of
      different ethnic groups. This article compares the MRI brain datasets of 10
      Chinese and 10 Caucasians. A statistical analysis was applied to the white matter
      volumes in these datasets and evaluate the dissimilarities between the two groups
      using various intuitive measures. This analysis has revealed systematic
      morphological differences between the two ethnic groups.

PMID- 16574580
TI  - A novel method for visualizing functional connectivity using principal component
      analysis.
AB  - Functional connectivity is a useful measure of voxel-wise functional magnetic
      resonance imaging signals that allows for the identification of functionally
      related brain areas and distributed networks. However, the high dimensionality of
      functional connectivity makes it difficult to visualize. In most studies, a small
      percentage of the total functional connectivity is visualized through diagrams
      that are constructed using individual seed voxels. In the present study describes
      a new method for visualizing most of the functional connectivity through a single
      diagram. This method does not rely on seed voxels, but rather employs a reduction
      of the high-dimensionality of the functional connectivity via a projection onto a
      three-dimensional color space using principal components analysis. With this new
      method, most of the information contained in a functional connectivity matrix can
      be represented through a single color-coded functional connectivity map, thereby
      facilitating a greater visual appreciation of functional connectivity.

PMID- 16574581
TI  - Visualization, reconstruction, and integration of neuronal structures in digital
      brain atlases.
AB  - Brain atlases are used in neuroanatomy to define the spatial layout of neuronal
      structures. Their digital variant can serve as a database and common reference
      frame for integrating data from different biological experiments. This article
      presents an overview of methods for three-dimensional visualization of
      neuroanatomical image data, reconstructing neuronal structures from image data,
      creating digital brain atlases, and registering data in an atlas. This enables
      analysis of spatial relations between individual structures imaged in different
      experiments as well as between these structures and the atlas.

PMID- 16574582
TI  - Visualizing neuronal structures in the human brain via diffusion tensor MRI.
AB  - Acquisition, analysis, and visualization of diffusion tensor magnetic resonance
      imaging (DT-MRI) is still an evolving technology. This article reviews the
      fundamentals of the data acquisition process and the pipeline leading to visual
      results that are interpretable by physicians in their clinical practice. The
      limitations of common approaches for visualizing the retrieved data are discussed
      and a new statistical method is presented to assess the reliability of the
      acquired tensor field. A novel visualization method is proposed which is
      discussed in light of neurophysiological considerations of the perception of
      colored patterns. It is argued that this method is more accurate for medical data
      while providing a nearly optimal visual stimulus. The method is evaluated on a
      patient study with a brain tumor.

PMID- 16574583
TI  - Recognition memory and awareness: A high-frequency advantage in the accuracy of
      knowing.
AB  - The well-established advantage of low-frequency words over high-frequency words
      in recognition memory has been found to occur in remembering and not knowing. Two
      experiments employed remember and know judgements, and divided attention to
      investigate the possibility of an effect of word frequency on know responses
      given appropriate study conditions. With undivided attention at study, the usual
      low-frequency advantage in the accuracy of remember responses, but no effect on
      know responses, was obtained. Under a demanding divided attention task at
      encoding, a high-frequency advantage in the accuracy of know responses was
      obtained. The results are discussed in relation to theories of knowing,
      particularly those incorporating perceptual and conceptual fluency.

PMID- 16574584
TI  - Islands of memory: Autobiographical remembering in amnestics.
AB  - In amnestics with anterograde amnesia, memories of post-onset autobiographical
      experiences, if present at all, are typically barren and impoverished. However,
      there have been sporadic reports of islands of memory--memories that are vivid,
      detailed, and specific to time and place. The aim of this study was to verify the
      presence of such memories and examine their incidence rate. Anterograde amnestics
      were interviewed in their home using a narrative interviewing strategy with a
      view to describing memory in everyday life. Each autobiographical memory of a
      post-onset event was coded for quantity-length, and quality-episodicity. In just
      over half of the amnestics (8 out of 14), a memory that was lengthy, rich in
      personal details, and localisable was recollected. The quantitative and
      qualitative aspects of these island memories were significantly different from
      the other autobiographical memories that the amnestics supplied. These memories
      were at odds with what would be expected on the basis of their performance on
      standardised memory instruments. Our findings suggest there is occasionally more
      variability in remembering of autobiographical experiences in some amnestics than
      has traditionally been believed.

PMID- 16574585
TI  - Higher face recognition ability in girls: Magnified by own-sex and own-ethnicity
      bias.
AB  - Earlier studies on adults have shown sex differences in face recognition. Women
      tend to recognise more faces of other women than men do, whereas there are no sex
      differences with regard to male faces. In order to test the generality of earlier
      findings and to examine potential reasons for the observed pattern of sex
      differences, two groups of Swedish 9-year-old children (n = 101 and n = 96)
      viewed faces of either Swedish or Bangladeshi children and adults for later
      recognition. Results showed that girls outperformed boys in recognition of female
      faces, irrespective of ethnicity and age of the faces. Boys and girls recognised
      Swedish male faces to an equal extent, whereas girls recognised more Bangladeshi
      male faces than boys did. These results indicate that three factors explain the
      magnitude of sex differences in face recognition: an overall female superior face
      recognition ability, the correspondence between the sex of viewer and the gender
      of the face, and prior knowledge of the ethnicity of the face.

PMID- 16574586
TI  - Impact of current grief on memory for past grief in spousal bereavement.
AB  - This study examined the impact of changes in level of current grief over time on
      changes in memory for past grief. Following from previous work on the impact of
      current affective state on memory for past affectively salient events, bereaved
      individuals who underwent a greater reduction in grief over time were expected to
      show a similar pattern of changes in memory for past grief. A sample of
      conjugally bereaved participants completed measures of current grief and memory
      for past grief at the time of the loss of their spouse at each of the 2, 6, 13,
      and 30 month post-loss time periods. As predicted, those who reported greater
      reduction in grief over the course of the study were more likely to remember
      their past grief as progressively less severe relative to those who underwent
      less reduction in grief over time. A nonrecursive causal model analysis verified
      that changes in memory for past grief were explained by changes in current grief.
      These results were discussed in terms of contemporary reconstructive memory
      accounts of the effect of affective state on memory.

PMID- 16574587
TI  - Congruency effect of presentation modality on false recognition of haptic and
      visual objects.
AB  - Studying a list of items related to an item that is not presented (lure item)
      produces a false memory. We investigated whether a haptic study/test results in
      false recognition and, if so, whether congruency of presentation modality between
      study and test reduces the false recognition. After haptic or visual study of
      lists of real objects that are related to a lure object, participants were asked
      to recognise whether the objects were presented haptically or visually. We
      obtained false recognition results with haptic study and/or test. False
      recognition was reduced when presentation and study modalities were congruent.
      After haptic study, false recognition was reduced in the haptic test, as compared
      to the visual test. In contrast, visual study always reduced visual false
      recognition. These results indicate that there is a general effect of retrieval
      cues that will reduce false recognition.

PMID- 16574588
TI  - Enhanced perceptual priming for neutral stimuli in a traumatic context: A pathway
      to intrusive memories?
AB  - Clinical observations suggest that re-experiencing symptoms are triggered by
      stimuli that are perceptually similar to those present shortly before the trauma
      or its worst moments. Two experiments investigated the possible role of
      perceptual priming in this phenomenon. Volunteers (N = 28, N = 62) watched a
      series of "traumatic" and neutral picture stories, and completed blurred object
      identification (priming) and recognition memory tasks. Neutral objects that
      immediately preceded the "traumatic" stories were more strongly primed, but not
      better recognised, than objects from neutral stories. Enhanced priming predicted
      subsequent re-experiencing symptoms. The results support the role of perceptual
      priming in re-experiencing.

PMID- 16574589
TI  - Follow-up of a cross-national comparison on flashbulb and event memory for the
      September 11th attacks.
AB  - Flashbulb memories are defined as vivid and long-lasting memories for the
      reception context of an important public event (Brown & Kulik, 1977). They are
      supposed to be triggered by both emotional reactions to the original event and
      rehearsal processes (Brown & Kulik, 1977; Finkenauer, Luminet, Gisle, El-Ahmadi,
      van der Linden, & Philippot, 1998; Neisser & Harsch, 1992). A test-retest design
      (21 vs 524 days after the event on average) was employed to assess flashbulb
      memory and event memory for the September 11th attacks and the impact of their
      emotional and rehearsal predictors in a sample of 985 respondents coming from six
      countries (i.e., Belgium, Italy, the Netherlands, Romania, Japan, and the USA).
      Results showed that national membership had a significant impact on event memory,
      and the emotional and rehearsal variables, but flashbulb memories for the
      September 11th attacks were found to be high and consistent across different
      countries. The implications of these findings for the debate about the nature and
      maintenance of flashbulb memories are discussed.

PMID- 16574590
TI  - Ageing affects conceptual but not perceptual memory processes.
AB  - Whereas age effects commonly occur in tests of explicit memory, tests of implicit
      memory often show age invariance. In two experiments, the traditional confound
      between test type (implicit vs explicit) and retrieval process (conceptually
      driven vs perceptually driven) was removed by using conceptually driven and
      perceptually driven tests of both implicit and explicit memory. Experiment 1
      revealed a significant age effect for conceptually driven retrieval and no age
      effect for perceptually driven retrieval, regardless of the type of memory being
      measured. Experiment 2 highlighted a difference between the two age groups in
      their ability to utilise semantic encoding in a nominally perceptually driven
      explicit memory test. The paper concludes that although perceptually driven
      processing is stable over age, particular care must be taken to minimise
      contamination from conceptually driven retrieval processes in such
      investigations.

PMID- 16574591
TI  - Autobiographical memories for places.
AB  - The purpose of the present exploratory study was to investigate operations and
      contents of a naturally occurring reminiscence for physical places in 26 Swedish
      participants. Using Conway and Pleydell-Pearce's (2000) model of autobiographical
      memory as a framework, two main questions were examined. First, in what sense are
      physical places ingredients of our selves-that is, of our self-knowledge-and, if
      so, how are they and their characteristics organised in the autobiographical
      knowledge base? Second, what form do personal memories for places take and what
      kinds of meanings and emotional contents do we bind to this type of reminiscence?
      The results showed that the Swedish participants' most important places in their
      lives were mainly childhood- and cottage-related rural types of milieus, and
      mostly categorised as summarised events; that is, frequently revisited. The
      personal recollections of the place-related event-specific knowledge were mostly
      of the generic imagery type, comprising semantic, perceptual, and emotional
      contents related to the "self", "others", and the "environment". The memories
      mainly reflected on the participants' growth period and feelings of activation
      and pleasantness. This was more pronounced in older (M = 59) than in younger (M =
      35) participants. All this indicates that physical places can serve as thematic
      pathways guiding reminiscence and self-knowing consciousness as we recollect
      details of perceptual, semantic, and emotional characters of periods in our
      lives.

PMID- 16574592
TI  - Language-dependent access to autobiographical memory in Japanese-English
      bilinguals and US monolinguals.
AB  - Japanese bilinguals retrieved autobiographical memories in response to 20 English
      and 20 Japanese cue words. US monolinguals were cued with 40 English words. All
      participants reported one earliest memory. Japanese bilinguals retrieved more
      memories and earlier memories when cued with Japanese words. They also retrieved
      more memories when the cue language matched either the language of memory
      encoding or the language of first thought. Although English cues elicited
      equivalent numbers of English and Japanese memories in the more fluent speakers
      of English, Japanese words elicited significantly larger numbers of Japanese
      memories in all Japanese-English bilinguals. The average age of cued
      autobiographical memories was significantly earlier for US than for Japanese
      students but age of the earliest memory did not differ.

PMID- 16574593
TI  - Acral and renal malformations following ICSI.
AB  - This case reports a delivery of a child with limb and renal malformations
      following intracytoplasmic sperm injection. A 29-year-old woman and a 39-year-old
      man with primary infertility underwent IVF-ICSI-ET therapy cycle. The couple
      delivered an infant with acrorenal syndrome. When assisted reproductive
      techniques are used, especially ICSI, the risk of genetics abnormalities should
      be discussed in detail with the couple and sufficient informed consent should be
      obtained before starting IVF-ET procedures.

PMID- 16574594
TI  - Viability and fecundity of human semen specimens cryostored and transported at 5
      degrees C using the Bio-Tranz shipping.
AB  - This study was designed to assess the viability and fecundity of semen stored at
      5 degrees C for 24 hours using the Bio-Tranz shipping system. Semen specimens
      were assessed for motility and sperm membrane integrity at the time of collection
      and 24 hours after storage in the Bio-Tranz. In group 1 (n = 61), specimens were
      diluted in TYB, processed and used for intrauterine insemination (IUI), leaving
      an aliquot for storage for 24 hours in the Bio-Tranz. In group 2 (n = 67),
      specimens were diluted in TYB, stored for 24 hours in the Bio-Tranz and then
      processed and used for IUI. In both groups, the total motile sperm used for IUI
      was similar and the women that underwent IUI were standardized for ovulation
      prediction and time of insemination. The overall sperm characteristics between
      the two groups were within normal range. Significant decreases were noted in
      sperm motility and membrane integrity in both groups after storage. Similar
      pregnancy rates were obtained between the two patient populations. The use of the
      Bio-Tranz shipper is extremely convenient for patients requiring semen
      evaluation, cryostorage or IUI and other assisted reproductive technologies.

PMID- 16574595
TI  - Association between lower urinary tract symptoms and erectile dysfunction.
AB  - Our aim was to assess the association between lower urinary tract symptoms (LUTS)
      and erectile dysfunction by means of International Prostate Symptom Score (IPSS)
      and Sexual Health Inventory for Men (SHIM) questionnaire. A total of 69 eligible
      patients who were admitted to our outpatient clinic with lower urinary tract
      symptoms were included in the study. A self administered questionnaire of IPSS
      and SHIM were given to patients. Demographics and medical history data were
      recorded. Any risk factor that may be associated with erectile dysfunction,
      including coronary artery disease, diabetes, hypertension, and smoking status,
      was determined in each patient. Correlation tests were used to examine the
      relationship between lower urinary tract symptoms and erectile dysfunction by
      controlling the effects of age and comorbidities. Mean age was 58.6 +/- 13.1 31
      86 years. Mean SHIM and IPSS total score was 14.3 +/- 7.5 and 11.5 +/- 8.1,
      respectively. Spearman correlation coefficient between IPSS and SHIM scores was
      found to be -0.41. There was a significant negative correlation with IPSS total
      scores of moderate degree when both age and presence of risk factor was
      controlled (r = -0.31; p = 0.009). Storage symptom scores showed significant
      correlation with SHIM scores (r = -0.33; p = 0.000). The association between SHIM
      score and each item of IPSS showed significant correlation for urgency, straining
      and nocturia when age controlled. The degree of bother by LUTS as determined by
      the IPSS quality of life question was also correlated with SHIM scores; however,
      this correlation was not significant when age or risk factor for ED was
      controlled. The presence of LUTS especially storage symptoms is strongly
      associated with erectile dysfunction independent of age and comorbidities.

PMID- 16574596
TI  - Efficacy of sildenafil for Japanese patients with audio-visual sexual stimulation
      (AVSS) test by the RigiScan Plus.
AB  - Sildenafil is most effective in men with mild-to-moderate ED, but not severe ED
      in Japan. In order to evaluate the efficacy of sildenafil, we conducted the
      present study using the AVSS test by the RigiScan Plus. The subjects were 56
      patients (age: 34-82 years, mean: 60.5 years) with ED. The IIEF5 questionnaire
      and the AVSS test were conducted before and after administration of sildenafil.
      The penile rigidity could not be measured in 19 patients. Of these 19, sildenafil
      was effective in 7 and not effective in 12. The 7 cases in whom sildenafil was
      effective were all false-negatives. The sensitivity of sildenafil was 84%, and
      its specificity was 100%. This study suggests that the AVSS test by RigiScan Plus
      can objectively evaluate the efficacy of sildenafil, and shows potential for
      predicting that efficacy.

PMID- 16574597
TI  - Screening of Y chromosome microdeletions in Tunisian infertile men.
AB  - The aim of this study was to establish the prevalence of Y chromosomal
      microdeletions in infertile Tunisian men. Three groups of infertile men, 65
      normospermic, 53 oligozoospermic and 45 azoospermic, were tested for Yq
      microdeletions detection by multiplex polymerase chain reaction (PCR) using
      specific Y chromosome AZF regions tagged site markers (STS). One group of 13
      healthy men was used as the control group. Six STS were tested (2 in each AZF
      region). The general prevalence of AZF microdeletions was 16%; in azoospermia and
      severe oligospermia groups, it was higher (29% and 30.5%, respectively).
      Significant differences were found with moderate oligospermic and normospermic
      groups (p < 0,05). AZFc microdeletions were the most frequent, and 55% of AZFc
      deleted patients were oligospermic. No deletions were detected in the control
      group. These results add to the growing literature data, showing that
      microdeletions of the Y chromosome is an important cause of severe
      spermatogenetic defect and confirm that deletion in AZFc region is the most
      common and is compatible with residual spermatogenesis.

PMID- 16574598
TI  - Evaluation of DAZ microdeletions in 34 infertile men.
AB  - Microdeletions in Yq11 are a common molecular cause of spermatogenic failure in
      men and are recurrently detected in about 10-15% of idiopathic azoospermia and
      severe oligozoospermia. Screening for AZF microdeletions is often performed by
      multiplex PCR. AZFc deletions, involving the DAZ gene, form the majority of these
      deletions. The aim of this study was to evaluate in a group of 34 Tunisian
      infertile patients (16 oligozoospermic and 18 azoospermic men) the prevalence of
      DAZ microdeletions using a rapid molecular strategy: the PCR-DGGE method based on
      the high degree of homology between the DAZ gene and its autosomally equivalent
      DAZLA gene. DAZ microdeletions were detected in 8.8% of patients. The three
      deleted patients have a 46, XY karyotype. Two of them were azoospermic and the
      other had an extreme oligo-asthenoteratozoospermia with a predominant
      abnormality: small round head spermatozoa (Y46). Our findings suggest that PCR
      DGGE method, for detection of DAZ gene deletion, could be particularly useful as
      a first step in the diagnosis workup of nonobstructive azoospermia and severe
      oligozoospermia for three reasons. First, it is a simple and fast system; second,
      DAZ microdeletions are the most common Y deletions; and third, partial DAZ
      microdeletions and mosaicism may be recognized by PCR-DGGE while only deletions
      removing the whole DAZ gene cluster can be detected by STS-PCR [211].
      Nevertheless, this procedure has limitations because other deletions of AZFa and
      AZFb may go undetected. Therefore, molecular investigation by multiplex PCR must
      be conducted in a second step according to European guidelines for the molecular
      diagnosis of Y chromosome microdeletions, particularly before ICSI procedures.

PMID- 16574599
TI  - High inguinal loupe-assisted varicocelectomy for subfertile men with
      varicococeles: technical feasibility, clinical outcomes and complications.
AB  - 254 consecutive patients underwent high inguinal loupe-assisted varicocelectomy.
      All patients had at least a one year history of infertility with abnormal semen
      parameters and physical examination and/or color Doppler ultrasound proven
      varicocele. To facilitate the procedure, an x 3.0 loupe was used during spermatic
      cord dissection near or at level of internal inguinal ring. Semen analysis and
      physical examination were performed at 3 monthly intervals. No intra-operative
      complications occurred. The most common post-operative complications were
      transient scrotal pain and stitch reaction, occurring in 12% and 4% of men,
      respectively. Only one permanent and two transient hydroceles were observed.
      Recurrent or persistent varicocele was identified by physical examination and
      color Doppler in 5 varicocelectomies (1.4%), and by color Doppler only in 6
      varicocelectomies (1.7%). Sperm motility increased from 30 +/- 8% to 46 +/- 20%,
      and sperm concentration. (10(6)/cc) increased from 24 +/- 18 to 41 +/- 28. The
      one-year pregnancy rate was 37%. High inguinal loupe-assisted varicocelectomy is
      a safe, simple, and effective treatment for varicocele.

PMID- 16574600
TI  - EXpression of ErbB proteins in human prostate.
AB  - ErbB proteins are widely expressed in human and animal tissues, notably in cells
      of epithelial or neuroendocrine origin. Protein expression and interactions of
      ErbBs were examined in prostate cancer specimens. Expression of ErbB1-4 proteins
      was determined with immunohistochemical methods using each monoclonal antibody in
      20 prostatic adenocarcinomas. The 4 ErbB proteins were widely expressed in
      normal, hyperplastic and cancerous tissues of the prostate. ErbBs may contribute
      to normal development or tumor growth and progression in human prostate.

PMID- 16574601
TI  - In vitro effects of epristeride on sperm in rats, dogs and man.
AB  - The study was conducted to evaluate in vitro effects of epristeride on sperm in
      rats, beagle dogs and man. Semen samples were divided into 4 groups and treated
      with vehicle and epristeride. Motility and motile rate of sperm were videotaped
      and analyzed with CASA system after 1 h and 2 h incubation periods. Percentage of
      motile sperm (MOT) of rat sperm decreased after the treatment with epristeride
      (final concentrations were 0.6, 6 and 60 micromol/L) for 1 h, and MOT of rat
      sperm treated with middle dose and high dose levels of epristeride also decreased
      after 2 h, while MOT of dog sperm that treated with three dose levels of
      epristeride decreased after 2 h. Amplitude of lateral head displacement (ALH) and
      MOT of human sperm decreased after 2 h with 4.8 micromol/L epristeride treatment.
      Curvilinear velocity (VCL) and straight-line velocity (VSL) of rat sperm and
      human sperm changed after 2 h, but there were no significant differences.
      Therefore, epristeride had a toxic effect on sperm, and the effect varied in
      different species.

PMID- 16574602
TI  - Sperm DNA fragmentation.
AB  - Several techniques have been developed to measure the amount of sperm DNA damage
      in an effort to identify more objective parameters for evaluation of infertile
      men. The integrity of sperm DNA influences a couple's fertility and helps predict
      the chances of pregnancy and its successful outcome. The available tests of sperm
      DNA damage require additional large-scale clinical trails before their
      integration into routine clinical practice. The physiological/molecular integrity
      of sperm DNA is a novel parameter of semen quality and a potential fertility
      predictor. Although DNA integrity assessment appears to be a logical biomarker of
      sperm quality, it is not being assessed as a routine part of semen analysis by
      clinical andrologists. Extensive investigation has been conducted for the
      comparative evolution of these techniques. However, some of these techniques
      require expensive instrumentation for optimal and unbiased analysis, are labor
      intensive, or require the use of enzymes whose activity and accessibility to DNA
      breaks may be irregular. Thus, these techniques are recommended for basic
      research rather than for routine andrology laboratories. Sperm chromatin
      structure evaluation is applied to detect male factors that may affect the chance
      of success with IVF as well as natural fertility. Further research is needed to
      define the optimal test of sperm chromatin structure. The clinical application of
      this test will evolve as well.

PMID- 16574603
TI  - Effect of lisnopril, an angiotensin converting enzyme (ACE) inhibitor on
      spermatogenesis in rats.
AB  - The role of ACE inhibitors (Lisinopril) in reproductive function remains
      controversial. Some benefits seem to be derivable even in non-hypertensive males
      with low doses. This study was done using rat model to establish this fact. Male
      rats were divided into different groups to receive different doses of lisinopril.
      A control group received no drugs. The mean arterial pressure fell the most with
      5 mg of lisinopril. The greatest increase in sperm count and motility was
      recorded for this same group. This response was dose dependent, falling as the
      drug dose fell. Lisinopril appeared to, in a dose dependent manner, improve sperm
      count and motility. In low doses, there is no significant change in arterial
      pressure. Infertile males with poor quality semen could benefit from a low dose
      of ACE inhibition. Where they are also hypertensive, ACE inhibition would be an
      appropriate first line treatment.

PMID- 16574604
TI  - Chronic propranolol treatment causes desensitization of the steroidogenic
      response in testicular interstitial cells but does not alter protein kinase C.
AB  - We investigated effects of chronic propranolol treatment on the secretory
      response of rat testicular interstitial cells (testosterone secretion) to
      subsequent in vitro stimulation with activators of protein kinase-C (PK-C) (L
      propranolol, phorbol 12, 13-dibutyrate (PDBu), LHRH) or activators of protein
      kinase A (PK-A), (hCG or dibutyryl cAMP (dbcAMP)). We determined [3H]PDBu binding
      and PK-C activity in these cells. Treatment of rats with propranolol (Inderal 500
      mg/L of water for 5 weeks) reduced by 48%, 50% and 29% the L-propranolol-, LHRH-
      or PDBu-induced testosterone secretion, respectively, when compared to cells from
      controls. This desensitization in testosterone secretion in vitro was also
      present when the testicular interstitial cells were stimulated with hCG or dbcAMP
      (secretion decreased by 65%/57%, respectively, when compared to cells from
      control rats). Challenging the cells originated from rats that received
      propranolol chronically with the addition in vitro of propranolol resulted in an
      additional reduction of the hCG/dbcAMP-stimulated testosterone secretion. Chronic
      propranolol-induced desensitization was not associated with a loss in [3H]PDBu
      binding or a decrease in PK-C activity. Chronic propranolol-induced
      desensitization can be uncoupled from down-regulation of protein kinase C. The
      effector responsible for the desensitization could be distal to the protein
      kinase C and protein kinase A.

PMID- 16574605
TI  - Postoperative changes of sperm chromatin heterogeneity, using acridine orange
      staining, in varicocele patients.
AB  - The aim of this study was to evaluate postoperative changes in sperm chromatin
      heterogeneity in varicocele patients. In 15 infertile patients with varicocele,
      sperm parameters including concentration, motility, and morphology were evaluated
      before and after surgical correction of varicocele. Sperm motion analysis using
      computer-assisted semen analyzer (CASA) was also performed. To analyze the sperm
      nuclear proteins, the acridine orange staining method was used. On semen
      analysis, sperm concentration and motility significantly increased after surgery
      (p = 0.002, p = 0.003, respectively), although sperm morphology was unaltered
      postoperatively. CASA parameters, including velocity, linearity, amplitude of
      lateral head displacement and beat cross frequency were unaltered
      postoperatively. On the other hand, acridine orange staining significantly
      increased postoperatively (p = 0.002). Varicocele influences the sperm chromatin
      condition, as well as sperm concentration and motility.

PMID- 16574606
TI  - Indicators of moisture and ventilation system contamination in U.S. office
      buildings as risk factors for respiratory and mucous membrane symptoms: analyses
      of the EPA BASE data.
AB  - We assessed associations between indicators for moisture in office buildings and
      weekly, building-related lower respiratory and mucous membrane symptoms in office
      workers, using the U.S. EPA BASE data, collected in a representative sample of
      100 U.S. office buildings. We estimated the strength of associations between the
      symptom outcomes and moisture indicators in multivariate logistic regression
      models as odds ratios (ORs) and 95% confidence intervals (CI), controlling for
      potential confounding factors and adjusting for correlation among workers in
      buildings. This analysis identified associations between building-related
      symptoms and several indicators of moisture or contamination in office buildings.
      One set of models showed almost a tripling of weekly building-related lower
      respiratory symptoms in association with lack of cleaning of the drip pans under
      air-conditioning cooling coils (OR [CI] = 2.8 (1.2-6.5)). Other models found that
      lack of cleaning of either drip pans or cooling coils was associated with
      increased mucous membrane symptoms (OR [CI] = 1.4 (1.1-1.9)). Slightly increased
      symptoms were also associated with other moisture indicators, especially mucous
      membrane symptoms and past water damage to building mechanical rooms (OR [CI] =
      1.3 (1.0-1.7)). Overall, these findings suggest that the presence of moisture or
      contamination in ventilation systems or occupied spaces in office buildings may
      have adverse respiratory or irritant effects on workers. The analysis, however,
      failed to confirm several risks identified in a previous study, such as condition
      of drain pans or outdoor air intakes, and other hypothesized moisture risks.
      Studies with more rigorous measurement of environmental risks and health outcomes
      will be necessary to define moisture-related risks in buildings.

PMID- 16574607
TI  - Respiratory protection from isocyanate exposure in the autobody repair and
      refinishing industry.
AB  - This study, part of the Survey of Painters and Repairers of Auto bodies by Yale
      (SPRAY), evaluated the effectiveness of respiratory protection against exposure
      to aliphatic polyisocyanates. A total of 36 shops were assessed for respiratory
      protection program completeness; 142 workers were measured for respirator fit
      factor (FF) using PortaCount Plus respirator fit tester. Twenty-two painters from
      21 shops were sampled using NIOSH method 5525 to determine the workplace
      protection factor (WPF) of negative pressure, air-purifying half-facepiece
      respirators equipped with organic vapor cartridges and paint prefilters during
      spray-painting and priming activities. Only 11 shops (30%) had written
      respiratory protection programs. Eighty percent of all fit tested workers passed
      the test on the first try with FF >or= 100, and 92% passed the second test after
      respirator use training. Overall geometric mean (GM) FF was 1012 for all fit
      tested workers. Significant differences on pass rate (92% vs. 72%) and on FF
      (1990 vs. 736) were found between previously fit tested workers vs. nontested
      workers. Twenty-nine WPF samples were collected. The outside facepiece GM
      concentration of total isocyanate group (NCO) was 378.4 micro g NCO/m(3) with 96%
      concentrations exceeding the U.K. short-term exposure limit, 70 micro g NCO/m(3),
      but no in-facepiece concentrations exceeded the limit. The GM WPF of total NCO
      was 319 (GSD 4) and the 5th percentile was 54. WPF of total NCO was positively
      correlated with the duration of painting task. FF positively correlated with WPF
      when FF was <or=450 but negatively correlated with WPF when FF was >450. We
      conclude that negative pressure, air-purifying half-facepiece respirators
      equipped with organic vapor cartridges and paint prefilters provide effective
      protection against isocyanate exposure in spray and priming operations if workers
      are properly trained and fitted.

PMID- 16574608
TI  - Acute respiratory syndrome after inhalation of waterproofing sprays: a posteriori
      exposure-response assessment in 102 cases.
AB  - Waterproofing agents are widely used to protect leather and textiles in both
      domestic and occupational activities. An outbreak of acute respiratory syndrome
      following exposure to waterproofing sprays occurred during the winter 2002-2003
      in Switzerland. About 180 cases were reported by the Swiss Toxicological
      Information Centre between October 2002 and March 2003, whereas fewer than 10
      cases per year had been recorded previously. The reported cases involved three
      brands of sprays containing a common waterproofing mixture, that had undergone a
      formulation change in the months preceding the outbreak. A retrospective analysis
      was undertaken in collaboration with the Swiss Toxicological Information Centre
      and the Swiss Registries for Interstitial and Orphan Lung Diseases to clarify the
      circumstances and possible causes of the observed health effects. Individual
      exposure data were generated with questionnaires and experimental emission
      measurements. The collected data was used to conduct numeric simulation for 102
      cases of exposure. A classical two-zone model was used to assess the aerosol
      dispersion in the near- and far-field during spraying. The resulting assessed
      dose and exposure levels obtained were spread on large scales, of several orders
      of magnitude. No dose-response relationship was found between exposure indicators
      and health effects indicators (perceived severity and clinical indicators). Weak
      relationships were found between unspecific inflammatory response indicators
      (leukocytes, C-reactive protein) and the maximal exposure concentration. The
      results obtained disclose a high interindividual response variability and suggest
      that some indirect mechanism(s) predominates in the respiratory disease
      occurrence. Furthermore, no threshold could be found to define a safe level of
      exposure. These findings suggest that the improvement of environmental exposure
      conditions during spraying alone does not constitute a sufficient measure to
      prevent future outbreaks of waterproofing spray toxicity. More efficient
      preventive measures are needed prior to the marketing and distribution of new
      waterproofing agents.

PMID- 16574610
TI  - Suicide among indigenous peoples: introduction and call to action.
AB  - Indigenous people around the world have the highest suicide risk of any
      identifiable cultural (or ethnic) group. It is a youth epidemic. The World Health
      Organization (WHO) has called for action; this special issue of Archives of
      Suicide Research (ASR) is an attempt to heed this call. Scholars, indigenous and
      non-indigenous, present data from the Arctic, Canada, Australia, New Zealand,
      Brazil, and other regions. It is concluded that not only data, but also
      explanations are needed. Suicide is multi determined. Colonialism and its
      associated genocide are, however, cited as a common factor. Yet, much greater
      cooperative international efforts are needed to not only understand, but also
      predict and control the epidemic.

PMID- 16574611
TI  - Suicide among indigenous peoples: a cross-cultural perspective.
AB  - The study of suicide in indigenous peoples is explored in different nations, both
      within nations containing many types of indigenous peoples and also across
      cultures. Some illustrations are given of how studies of indigenous peoples can
      be used both to test existing theories of suicide and generate new theories of
      suicide.

PMID- 16574612
TI  - Changing selves in changing worlds: youth suicide on the fault-lines of colliding
      cultures.
AB  - What does it mean to somehow override change and to count one's self as one and
      the same individual, continuous in time? What does "continuity" mean for whole
      cultural groups? How might disruptions to a sense of personal or cultural
      persistence deprive us of a past, and a connection to our as yet unrealized
      futures? Why is it that the bulk of us who succeed in knitting up our raveled
      sleeves of care choose for life, while those who loose the thread of their
      continuous existence so frequently make the opposite choice? The program of
      research outlined here--work that explores the relation between markers of self-
      and cultural continuity, and suicidal behaviors in both culturally mainstream and
      Canadian Aboriginal youth--provides evidence that personal persistence and
      persistent peoples have low or absent rates of youth suicide, while individuals
      and communities lacking a requisite sense of continuity regularly suffer suicides
      in epidemic numbers.

PMID- 16574613
TI  - Aboriginal and Torres Strait Islander suicide in context.
AB  - Aboriginal and Torres Strait Islander suicide has been an issue of national
      public health and mental health concern for only one decade, having increased
      dramatically from levels that were very low in the late 1980s to levels of young
      adult male suicide that are now substantially higher than for the non-indigenous
      population. In this review the authors socially and historically contextualize
      these changes, identifying the causal frameworks adopted in developing
      interventions, and present an explanation in narrative and pictorial form that
      draws on critical family-centered trauma.

PMID- 16574614
TI  - Suicide prevention efforts in one area of Indian Health Service, USA.
AB  - Suicide is the second leading cause of death in young Indian people. USA's Indian
      Health Service is responsible for the health of the people; a structured system
      and services are provided. These services include surveillance and suicide
      investigation, to allow for better understanding. This article presents the
      current epidemiology on suicide for American Indians and Alaskan Natives (AI/AN).
      The data show a very high rate in the young, especially males. Beyond the
      general, the article offers a unique look into a suicidal AI/AN young person,
      through the psychological autopsy. A case illustration, E.S., a 16-year-old male
      who died by suicide, is outlined. Discussion, the author's words, and current
      efforts of Indian Health Services are presented, but it is concluded that much
      greater effort is needed.

PMID- 16574615
TI  - Suicidal ideation among American Indian youths.
AB  - This study examined correlates of suicidal ideation among 212 American Indian
      youth who lived on or near three reservations in the upper Midwestern United
      States. The youths were, on average, 12 years old, and 9.5% reported current
      thoughts about killing themselves. Females were over 2 times more likely than
      males to think about suicide. Multivariate logistic regression results indicated
      that gender, enculturation, negative life events, perceived discrimination, self
      esteem, and drug use were related to the likelihood of thinking about suicide.
      Drug use was the strongest correlate of suicidal ideation, and both enculturation
      and perceived discrimination emerged as important culturally specific variables.
      It was suggested that suicide prevention programs should draw on the strengths of
      American Indian culture.

PMID- 16574616
TI  - Suicide among Guarani Kaiowa and Nandeva youth in Mato Grosso do Sul, Brazil.
AB  - Information on morbidity and mortality are critical for developing appropriate
      prevention and health promotion programs. This study summarizes data on the
      Guarani (Kaiowa and Nandeva) communities in Mato Grosso do Sul, Brazil, about
      which little addressing suicide has been documented. Epidemiologic and
      anthropological data were used to examine suicidal behavior in these indigenous
      communities. Several findings in this report about the Guarani Kaiowa and Nandeva
      communities were remarkable: the rates of suicide among these communities appear
      higher than the national average; suicide deaths disproportionately affect
      adolescents and young adults; and suicide rates among young males appear to be
      increasing. Data in this report highlight the need for health information data
      specific to a community in order to identify emerging health problems.

PMID- 16574617
TI  - Suicide--a challenge in modern Greenland.
AB  - The incidence of youth suicides has increased dramatically among the Inuit in
      Greenland since the modernization started in the 1950s. Suicides currently peak
      at age 15-24 Men: 400-500, Women: 100-150 per 100,000 person-years. The methods
      are drastic: shooting or hanging. An early peak was seen in the capital, a later
      peak in the rest of West Greenland, and high and increasing rates in remote East
      Greenland. Suicidal thoughts occur more often in young people who grew up in
      homes with a poor emotional environment, alcohol problems and violence. There is
      a definite correlation with several aspects of the modernization process but it
      is hard to pinpoint causal relationships. It is rather the "modernization
      package" that should be regarded as risk factors for suicides.

PMID- 16574618
TI  - Suicide in Siberian aboriginal groups.
AB  - A search of historical documents about suicide in Siberian tribes in the 18th and
      19th centuries indicated that they had very high suicide rates. It would be of
      great interest to explore suicidal behavior in these tribes today.

PMID- 16574619
TI  - A new model for investigating the mortality effects of multiple air pollutants in
      air pollution mortality time-series studies.
AB  - Because the U.S. Environmental Protection Agency regulates air pollutants
      independently, the majority of time-series studies on air pollution and mortality
      have focused on estimating the adverse health effects of a single pollutant.
      However, due to the sometimes high correlation between air pollutants, the
      results from studies that focus on a single air pollutant can be difficult to
      interpret. In addition, the high correlation between air pollutants can produce
      problems of interpretation for the standard method of investigating the adverse
      health effects due to multiple air pollutants. The standard method involves
      simultaneously including the multiple air pollutants in a single statistical
      model. Because of this, the development of new models to concurrently estimate
      the adverse health effects of multiple air pollutants has recently been
      identified as an important area of future research. In this article, a new model
      for disentangling the joint effects of multiple air pollutants in air pollution
      mortality time-series studies is introduced. This new model uses the time-series
      data to assign each air pollutant a weight that indicates the pollutant's
      contribution to the air pollution mixture that affects mortality and to estimate
      the effect of this air pollution mixture on mortality. This model offers an
      improvement in statistical estimation precision over the standard method. It also
      avoids problems of interpretation that can occur if the standard method is used.
      This new model is then illustrated by applying it to time-series data from two
      U.S. counties.

PMID- 16574620
TI  - Elimination half-lives of selected polychlorinated dibenzodioxins and
      dibenzofurans in breast-fed human infants.
AB  - Elimination half-life estimates for several polychlorinated dibenzodioxins/furans
      (PCDD/F) were calculated by modeling the blood and breast milk concentrations in
      two breast-fed human infants as reported by Abraham et al. (1996, 1998). Our
      analysis differs from that of other investigators in that we analyzed individual
      dioxin and furan congeners while the other studies considered TCDD only and we
      determined the half-lives in infants, rather than simply predicting body burdens
      in infants and older children. The average half-life values for each consistently
      measurable congener were determined to be less than about 6 mo and did not vary
      substantially between the two infants studied. The average elimination half-life
      values for 2,3,7,8-tetraCDD, 1,2,3,7,8-pentaCDD, 1,2,3,6,7,8-hexaCDD,
      1,2,3,4,6,7,8-heptaCDD, and octaCDD were 0.40, 0.32, 0.39, 0.32, and 0.46 yr,
      respectively, and 0.27 yr for 2,3,4,7,8-pentaCDF. These values are in stark
      contrast with the 7 to 15+ yr values reported for these congeners in human adults
      (Michalek et al., 1996). These much shorter half-life values, likely attributable
      to rapid growth of the adipose tissue volume and enhanced fecal excretion of
      dioxins for breast-fed infants, explain why the much higher daily dioxin intake
      during breastfeeding does not translate to proportionately higher tissue
      concentrations. Thus, the shorter half-life of dioxins during breastfeeding needs
      to be considered when evaluating the dioxin hazard to children.

PMID- 16574621
TI  - A dose-response study of the effects of prenatal and lactational exposure to TCDD
      on the immune response to influenza a virus.
AB  - The goal of the current study was to evaluate the immune response to a common
      respiratory pathogen, influenza A virus, in mice exposed to increasing doses of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during development. Additionally, the
      treatment paradigm was designed to provide exposure throughout fetal and neonatal
      development, beginning on d 1 of gestation. To accomplish this, impregnated
      C57Bl/6 mice were treated with 0.25 microg/kg TCDD on d 0 and 7 of pregnancy,
      followed by 2 additional doses of 0.25, 1, or 5 microg/kg given on d 14 and
      postpartum d 2. The adult offspring were infected with influenza virus, and
      components of the adaptive and innate immune responses were evaluated. Our
      results show that developmental exposure to TCDD dose-responsively suppressed
      both the cell-mediated and antibody responses to influenza virus in female but
      not males. In contrast, TCDD exposure enhanced the innate immune responses in
      offspring of both sexes; specifically, neutrophilia and interferon (IFN) gamma
      levels in the lung were increased. These alterations in functional immunity did
      not result from overt toxicity to the immune organs, as developmental TCDD
      exposure did not alter the cellular composition of the thymus, spleen, or bone
      marrow. These findings extend our knowledge of the dose-responsive nature of
      immunological defects induced by developmental exposure to TCDD and offer insight
      regarding the dose required to alter the immune response to viral infection.
      Moreover, we demonstrate a clear dose at which no observable effects on immune
      function later in life were detected.

PMID- 16574622
TI  - Increased susceptibility of hyperthyroid rats to ozone: early events and
      mechanisms.
AB  - Previous studies demonstrated that ozone-induced lung damage and inflammation are
      much greater in hyperthyroid rats, compared to normal rats, at 18 h postexposure.
      The purpose of the present investigation was to study early events and mechanisms
      underlying the increased sensitivity to ozone in a hyperthyroid state.
      Specifically, the degree of lung epithelial cell barrier disruption, the
      antioxidant status of the extracellular lining fluid, and the release of
      inflammatory mediators were examined. To induce a hyperthyroid state, mature male
      Sprague-Dawley rats were implanted with time-release pellets containing
      thyroxine; control rats received placebo pellets. After 7 d, the animals were
      exposed to air or ozone (2 ppm, 3 h). Immediately following the end of the
      exposure, bronchoalveolar lavage (BAL) fluid and cells were harvested. BAL fluid
      albumin levels and total antioxidant status were examined. In addition, levels of
      prostaglandin E2 (PGE2), macrophage inflammatory protein (MIP)-2, MCP-1, and
      tumor necrosis factor (TNF)-alpha were determined in BAL fluid and in media
      samples following ex vivo culture of BAL cells harvested after in vivo inhalation
      exposures. The results of this study are consistent with the following
      hypotheses: (1) A marked increase in the permeability of the alveolar-capillary
      barrier is an early event following ozone exposure in a hyperthyroid state;
      however this does not appear to be due to overall changes in BAL fluid
      antioxidant potential. (2) Early increases in MIP-2, but not PGE2, are involved
      in the enhanced lung response to ozone in a hyperthyroid state. (3) Inflammatory
      mediator production (i.e., PGE2, MIP-2, MCP-1, and TNF-alpha) by alveolar
      macrophages plays a minimal role in the initial responses to ozone in a
      hyperthyroid state.

PMID- 16574623
TI  - Exposure in vivo to silica or lipopolysaccharide produces transient or sustained
      upregulation, respectively, of PYPAF7 and MEFV genes in bronchoalveolar lavage
      cells in rats.
AB  - A family of proteins containing PAAD [for PYRIN, AIM (absent in melanoma),
      apoptosis-associated protein speck-like protein containing a caspase recruitment
      domain, and death domain] domain was found to be involved in modulating
      inflammatory responses, by its ability to regulate nuclear factor (NF)-kappaB and
      procaspase-1 activation. In this study, intratracheal instillation of silica in
      rats was found to produce transient upregulation of mRNA levels of the PAAD
      family of proteins, PYPAF7 (PYRIN containing Apaf1-like protein; Apaf stands for
      apoptosis activating factor) and MEFV (for Mediterranean fever), in
      bronchoalveolar lavage (BAL) cells. The levels were markedly elevated at 4 h,
      returning to basal levels by 24 h. In contrast, intratracheal instillation of LPS
      produced a sustained upregulation of the two genes in BAL cells. In vitro
      exposure of BAL cells to silica or lipopolysaccharide (LPS) produced no changes
      in the expression of these genes, indicating that silica or LPS exposure in vivo
      induces some factors that are responsible for the upregulation of PYPAF7 and
      MEFV. The mRNA levels of these two genes in peripheral blood monocytes and PMN
      following LPS exposure did not change, indicating that AM and peripheral blood
      cells show similar response to LPS exposure in vitro. This study provides the
      basis for a physiological model to study the effects of these two genes in
      modulating the inflammatory response after particle exposure.

PMID- 16574624
TI  - Dibromoacetic acid, a commonly occurring water disinfection by-product, does not
      affect follicular populations in neonatal rats.
AB  - To investigate whether the mechanism of dibromoacetic acid (DBA) toxicity
      involves disruption of primordial germ cell migration and/or follicular
      formation, pregnant and lactating female Sprague-Dawley rats were gavaged daily
      with 0, 1, 5, or 50 mg DBA/kg body weight beginning on gestation day 17 and
      continuing through postnatal day 7. Reproductive parameters in 4 groups (n = 10
      per group) of female neonatal rats exposed to DBA were examined. Maternal weight,
      litter size, and gender ratio did not differ across treatment groups, and major
      organ weights (spleen, liver, kidneys, uterus, and ovary) did not differ from
      control. Ovaries were serially sectioned at 8 microm and every eighth section was
      used for morphometry. All healthy follicles within a section were categorized
      into one of five types and the area of section was measured. Follicular
      populations at all stages of development did not differ among treatment groups.
      Thus, exposure to DBA during the period of follicular formation did not affect
      follicular populations in neonatal rats. These data suggest that rodents may not
      be a useful model for DBA toxicity assessment. Further research into species
      differences in the mechanism and timing of DBA toxicity is warranted.

PMID- 16574625
TI  - Pattern of sildenafil calls to Texas poison control centers, 1998-2004.
AB  - Sildenafil, a popular medication approved for the treatment of erectile
      dysfunction, is often misused. This study sought to describe the patterns of
      sildenafil calls to poison control centers in Texas during 1998-2004. Data on all
      sildenafil calls reported to the Texas Poison Center Network were analyzed. There
      were 628 sildenafil calls, 36% of which were human exposures and 44% were drug
      identifications. The number of calls increased during 1998-2003 but leveled off
      in 2004. The sildenafil exposure was isolated in 70% of the human exposure calls
      and involved other substances in 30% of the calls. Nonisolated exposures were
      more likely than isolated exposures to be intentional, involve males, occur in
      adults, and involve more serious problems as reflected by higher rates of health
      care facility treatment usage and more severe medical outcomes. The most
      frequently reported clinical effects were dizziness, tachycardia, erythema, and
      drowsiness. Most sildenafil calls were for human exposures or drug
      identification. The characteristics of human exposures such as the exposure
      reason and medical outcome were dependent on the presence of other substances.

PMID- 16574626
TI  - The effect of xenobiotic exposure on spontaneous autoimmunity in (SWR x SJL)F1
      hybrid mice.
AB  - F1 hybrids of SWR (H-2(q)) and SJL (H-2(s)) mice spontaneously develop a
      lupuslike condition in an age-dependent manner, and these two H-2 haplotypes also
      confer susceptibility to induction of systemic autoimmunity by heavy metals such
      as mercury, silver, and gold with anti-fibrillarin antibodies (AFA) as marker.
      The aim of this study was to determine how the mixing of two susceptible genomes
      might influence expression of idiopathic and induced autoimmunity over a period
      of 14 mo of exposure to mercury and silver. Spontaneous autoimmunity first
      appeared as antinuclear antibodies (ANA) in females at 10 wk of age and in males
      at 10 mo of age, and was followed by development of anti-chromatin antibodies.
      Antibodies to double-stranded DNA developed in 60% of males and 20% of females.
      Thirty percent of males and 10% of females developed a coarsely speckled ANA
      pattern associated with high titers of anti-Sm antibodies. Glomerular immune
      complex (IC) deposits and a proliferative glomerulonephritis were seen at 17 mo
      of age. The F1 hybrids treated with metals showed no exaggeration of spontaneous
      autoimmunity. However, the metals suppressed the spontaneous development of anti
      Sm and antichromatin antibodies. The metal-induced AFA, linked to the H-2(s) and
      H-2(q) haplotype, reached a maximum after 3-4 mo of treatment and then declined;
      33% of the silver-treated hybrids finally became AFA-negative, despite continuous
      treatment. The decline in ANoA during metal treatment is contrary to the
      situation in metal-treated SJL mice. This indicates that dominant SWR background
      genes suppressed induction of certain autoimmune traits in the (SWR x SJL)F1
      hybrid mice.

PMID- 16574627
TI  - Estrogens and brain function.
AB  - Cognitive decline is well recognized during ageing but is often accelerated in
      women after menopause. Studies have shown that there are significant gender
      differences in brain ageing with significantly greater changes in brain
      structure, function and metabolism between females and males. Estrogens exert
      protective effects on neuronal cells in culture but the exact underlying
      mechanism for their neuroprotective effect in humans is not completely
      understood. Estrogens have been shown to affect the nervous system in many
      different ways: via binding to estrogen receptors (ERs) but also via multiple
      pathways. The results of small randomized trials and larger observational studies
      suggest a beneficial effect of estrogen therapy on cognitive function in
      symptomatic postmenopausal women. However, the results of the Women's Health
      Initiative Study (WHIMS) do not support this, at least not in women over the age
      of 65. Alzheimer's disease (AD) is two to three times more common in women than
      in men. Based on currently available data, routine therapeutic use of estrogens
      in women with AD is not justified but it may have a role in the prophylaxis of
      AD. The existing evidence supports the use of HRT only in women with menopausal
      symptoms for a few years following menopause.

PMID- 16574628
TI  - Weightlessness and skeleton homeostasis.
AB  - As human beings venture into space in the 21st century, they will be confronted
      with a "hypodynamic" and thus hostile environment for the bone homeostasis, that
      could potentially compromise their mobility in general and skeletal strength in
      particular after landing. From this point of view, space flight studies are
      especially interesting and intriguing models for scientists. Space studies,
      however, must not only overcome enormous technical problems but are also limited
      in size and frequency. Therefore, ground-based models have also been developed to
      evaluate the effects of skeletal unloading. The most popular model for human
      studies is prolonged bed rest with normal volunteers, although studies with
      paraplegics have also been undertaken. In animals, the hindlimb elevation (tail
      suspension) model simulates space flight models and is well tolerated by the
      animals with minimal evidence of stress. Although negative calcium balance and
      bone loss have been observed in all the aforementioned models of skeletal
      unloading, the exact mechanism(s) by which this occurs are still unknown and
      mainly speculative.

PMID- 16574629
TI  - Advanced glycation end products and diabetic complications: a general overview.
AB  - Diabetes mellitus, especially type 2 diabetes is increasing at an alarming rate
      reaching epidemic proportions. Although hyperglycemia has been considered as
      playing an important role in the pathogenesis of diabetic complications, the
      mechanisms involved remain uncertain. There are several theories as to how
      chronic hyperglycemia can lead to micro or macrovascular disease in diabetes,
      including the advanced glycation end product (AGE) theory. Evidence for the
      effect of AGE in the development of diabetic angiopathy is derived not only from
      a number of in vitro and in vivo studies exploring the role of AGE in different
      pathologies, but also from studies demonstrating significant improvements of
      features of diabetic complications by anti-AGE agents. Although it is well
      established that AGE are involved in the pathogenesis of diabetic complications,
      more studies are needed to elucidate the exact role of AGE in this area. The use
      of the "new" and "old" anti-AGE agents will help both in the study of the
      mechanisms involved and the therapeutic applications aiming at prevention or
      amelioration of diabetic complications that still constitute a major problem with
      a life-threatening impact for diabetic patients, worldwide.

PMID- 16574630
TI  - Applications of genomic medicine in endocrinology and post-genomic endocrine
      research.
AB  - In the mid 1980's, two advances revolutionized Medicine in a way that is
      comparable only to some of the most important events in the approximately 3,000
      years of its history. The first was the introduction of the concept of
      "positional cloning", i.e. the idea that one can identify genes for human disease
      though knowing nothing or very little about their function. The second was the
      discovery of the method of polymerase chain reaction (PCR) which made DNA easier
      to work with for all biomedical researchers and clinicians. Fresh in the history
      of Endocrinology were the great discoveries of neuroendocrinology, and even more
      contemporary and potent, the influence of the then emerging field of molecular
      endocrinology. Cancer medicine and traditional human genetics were the fields
      that benefited most from the first applications of the new genomic concepts and
      technologies. Almost two decades later, and after the first successful
      applications of positional cloning in Endocrine Genetics with the identification
      of RET, menin, PTEN and PRKAR1A in the various forms of multiple endocrine tumor
      syndromes, and a number of other genes in developmental diseases affecting the
      pituitary, thyroid, parathyroid, pancreas, adrenal and gonadal glands,
      endocrinology has made a comeback to the forefront of "genomically"- influenced
      as well as post-genomic Medicine. This report, using the example of endocrine
      tumor genetics, presents the process and some of the accomplishments of
      positional cloning and discusses the influence of endocrinology on contemporary
      translational research. The author suggests that some of the most traditional
      endocrine concepts, established in the previous two centuries, could help us
      understand the complex pathways recently unraveled in cancer genetics and,
      consequently, other fields. It is suggested that "Endocrine" genes that control
      cellular signaling act as "conductor" since they regulate differentiation, growth
      and proliferation. Their complex function and resultant "transcriptomes" are now
      being investigated by post-genomic Medicine. In cancer research, endocrine genes
      defy classic definitions of tumor suppressors and oncogenes and regulate
      gatekeepers, caretakers, and landscapers. In the post-genomic, translational
      Medicine, Endocrinology once again could help us to understand cellular
      regulation and pathophysiology and to design new treatments.

PMID- 16574631
TI  - Chronic autoimmune thyroid disease in children and adolescents in the years 1999
      2004 in Lower Silesia, Poland.
AB  - The aim of the study was to analyze data related to chronic autoimmune thyroid
      disease at diagnosis and at follow-up of children and adolescents in Lower
      Silesia in the years 1999-2004. Age, gender, incidence of thyroid disease in the
      family, clinical presentation, hormonal findings, levels of thyroid antibodies,
      results of ultrasonography, and fine needle aspiration biopsy (FNAB) were
      recorded. 100 children, 10 boys and 90 girls, were included in the analysis. The
      mean age at diagnosis was 12.3+/-2.3 years and at last examination 14.9+/-1.9
      years. At diagnosis, increased levels of TSH without overt hypothyroidism was
      observed in 26 children. In 11 children hyperthyroidism was detected whereas 63
      children were euthyroid. An increased level of thyroid peroxidase antibodies was
      observed in 65% of the children. Ultrasonography was characteristic for
      Hashimoto's thyroiditis in all patients. Fine needle biopsy was performed when
      there were diagnostic difficulties (35% children). Thus, in all the children the
      diagnosis of Hashimoto's thyroiditis was ascertained either by high antibody
      titer or FNAB. Associated diseases were observed in 33% of the children. Thyroid
      disease in the family was present in 25% of the children. There was a gradual
      decline in the number of new cases presented from 1999 to 2004. The reason for
      this decline remains speculative.

PMID- 16574632
TI  - Of temples and plane trees: the Hippocratic legacy as collective memory.

PMID- 16574633
TI  - Violent media consumption and the recognition of dynamic facial expressions.
AB  - This study assessed the speed of recognition of facial emotional expressions
      (happy and angry) as a function of violent media consumption. Color photos of
      calm facial expressions morphed to either an angry or a happy facial expression.
      Participants were asked to make a speeded identification of the emotion
      (happiness or anger) during the morph. Results indicated that, independent of
      trait aggressiveness, participants high in violent media consumption responded
      slower to depictions of happiness and faster to depictions of anger than
      participants low in violent media consumption. Implications of these findings are
      discussed with respect to current models of aggressive behavior.

PMID- 16574634
TI  - Support for emergency department screening for intimate partner violence depends
      on perceived risk.
AB  - Emergency department (ED) screening for intimate partner violence (IPV) faces
      logistic difficulties and has uncertain efficacy. We surveyed 146 ED visitors and
      108 ED care providers to compare their support for ED IPV screening in three
      hypothetical scenarios of varying IPV risk. Visitor support for screening was 5
      times higher for the high-risk (86%) than for the low-risk (17%) scenario.
      Providers showed significantly more support for the need for ED IPV screening
      than visitors. Controlling for confounding by gender, race, experience with IPV,
      hospital, and marital status did not affect comparisons between groups. These
      responses indicate greater support for IPV screening in the ED for high-risk than
      for low-risk cases, particularly among visitors.

PMID- 16574635
TI  - The relationships among self-blame, psychological distress, and sexual
      victimization.
AB  - The primary purpose of this investigation is to assess the factor structure of
      survivors' attributions for previously experienced sexual assaults. Two hundred
      twenty-four female survivors of sexual assault responded to measures assessing
      attributions for past assaults, perceived avoidability of future assaults,
      frequency of past victimizations, and psychological distress. Factor analysis of
      the attributions measure suggested five underlying factors: perpetrator blame,
      characterological self-blame, situational factors and/or chance blame, behavioral
      self-blame, and societal blame. Results indicated that characterological self
      blame, but not behavioral self-blame, was associated with negative outcomes,
      including increased psychological distress and increased frequency of past
      victimization. Although behavioral self-blame was associated with perceived
      avoidability of future assaults, it was not associated with lower psychological
      distress or reduced frequency of past victimizations.

PMID- 16574636
TI  - Cross-validation of the risk matrix 2000 sexual and violent scales.
AB  - The predictive accuracy of the newly developed actuarial risk measures Risk
      Matrix 2000 Sexual/Violence (RMS, RMV) were cross validated and compared with two
      risk assessment measures (SVR-20 and Static-99) in a sample of sexual (n= 85) and
      nonsex violent (n= 46) offenders. The sexual offense reconviction rate for the
      sex offender group was 18% at 10 years follow-up, compared with 2% for the
      violent offenders. Survival analyses revealed the violent offenders were
      reconvicted at twice the rate compared to sexual offenders. The RMV significantly
      predicted violent recidivism in the sex and combined sex/violent offender groups.
      Although the RMS obtained marginal accuracy in predicting sexual reconviction in
      the sex offender group, none of the scales significantly predicted sexual
      reconviction. An item analysis revealed four factors not included in the risk
      scales that were significantly correlated with sexual and violent reconviction.
      Combining these factors with Static-99, RMV, and RMS increased the accuracy in
      predicting sexual reconviction.

PMID- 16574637
TI  - A lifetime of intimate partner violence: coping strategies of older women.
AB  - Little is known about how older women cope in long-term abusive intimate
      relationships. Understanding their coping strategies may give insight into how to
      further support their effective coping efforts. Interviews were conducted with 38
      women older than age 55 years. Grounded theory analysis demonstrated that women
      who remained in their abusive relationships employed mainly cognitive (emotion
      focused) strategies to find meaning in a situation that was perceived as
      unchangeable. By reappraising themselves, their spouses, and their relationships
      they refocused energies in certain roles, set limits with their abusers, and
      reached out to others (friends, family, and community organizations). Some women
      appeared to thrive, others merely survived, but all maintained the appearance of
      conjugal unity.

PMID- 16574638
TI  - Child sexual abuse, coping responses, self-blame, posttraumatic stress disorder,
      and adult sexual revictimization.
AB  - The present study examined the psychological sequelae of child sexual abuse (CSA)
      and the factors that contributed to revictimization in the form of adult sexual
      assault (ASA) using a survey of 577 female college students. CSA characteristics,
      maladaptive coping in response to CSA, degree of self-blame at the time of the
      abuse and currently, and posttraumatic stress disorder (PTSD) symptoms were
      examined as predictors of revictimization. Results indicated that individuals who
      reported both CSA and ASA had more PTSD symptoms, were more likely to use drugs
      or alcohol to cope, act out sexually, withdraw from people, and seek therapy
      services. In addition, the revictimized group reported more self-blame at the
      time of the abuse and currently. The only factor that predicted revictimization
      in this study was the number of maladaptive coping strategies used. Implications
      of these findings are discussed.

PMID- 16574639
TI  - A prospective analysis of juvenile male sex offenders: characteristics and
      recidivism rates as adults.
AB  - This research assesses the recidivism rates of a sample of 300 registered male
      sex offenders who were juveniles at the time of their initial arrest for a sex
      offense. This sample is followed for 3 to 6 years after they reached adulthood;
      recidivism rates are assessed during their adulthood only. The typical juvenile
      is a 15-year-old Caucasian male who was arrested for sexual assault or indecency
      with a child. The majority of the victims are females with an average age of 8.
      Although only 13 are rearrested during the follow-up period for a sex offense,
      more than half of the sample is arrested at least once for a nonsexual offense.
      The results of a Cox regression indicate that victim age, offender age, and
      victim sex are significant predictors of recidivism during adulthood.

PMID- 16574640
TI  - The traumatic impact of the September 11, 2001, terrorist attacks and the
      potential protection of optimism.
AB  - This study examined the impact of the September 11 terrorist attacks on graduate
      and undergraduate students and the role of optimism in posttraumatic distress. A
      sample of 457 students who attended courses at three schools of social work
      (Nevada, Pennsylvania, and Washington) participated in the study. A quarter of
      them had a known person as an immediate victim of the attacks. Multivariate
      analysis showed that posttraumatic stress disorder symptom scores were positively
      related to personal loss and two types of previous trauma reactivated by the
      attacks, and levels of initial negative emotional response. Optimism and its
      interaction with personal loss were inversely associated with posttraumatic
      stress disorder symptom scores.

PMID- 16574641
TI  - An integrated machine learning system to computationally screen protein databases
      for protein binding peptide ligands.
AB  - A fairly large set of protein interactions is mediated by families of peptide
      binding domains, such as Src homology 2 (SH2), SH3, PDZ, major histocompatibility
      complex, etc. To identify their ligands by experimental screening is not only
      labor-intensive but almost futile in screening low abundance species due to the
      suppression by high abundance species. An ideal way of studying protein-protein
      interactions is to use high throughput computational approaches to screen protein
      sequence databases to direct the validating experiments toward the most promising
      peptides. Predictors with only good cross-validation were not good enough to
      screen protein databases. In the current study we built integrated machine
      learning systems using three novel coding methods and screened the Swiss-Prot and
      GenBank protein databases for potential ligands of 10 SH3 and three PDZ domains.
      A large fraction of predictions has already been experimentally confirmed by
      other independent research groups, indicating a satisfying generalization
      capability for future applications in identifying protein interactions.

PMID- 16574642
TI  - Thioredoxin is required for deoxyribonucleotide pool maintenance during S phase.
AB  - Thioredoxin was initially identified by its ability to serve as an electron donor
      for ribonucleotide reductase in vitro. Whether it serves a similar function in
      vivo is unclear. In Saccharomyces cerevisiae, it was previously shown that
      Deltatrx1 Deltatrx2 mutants lacking the two genes for cytosolic thioredoxin have
      a slower growth rate because of a longer S phase, but the basis for S phase
      elongation was not identified. The hypothesis that S phase protraction was due to
      inefficient dNTP synthesis was investigated by measuring dNTP levels in
      asynchronous and synchronized wild-type and Deltatrx1 Deltatrx2 yeast. In
      contrast to wild-type cells, Deltatrx1 Deltatrx2 cells were unable to accumulate
      or maintain high levels of dNTPs when alpha-factor- or cdc15-arrested cells were
      allowed to reenter the cell cycle. At 80 min after release, when the fraction of
      cells in S phase was maximal, the dNTP pools in Deltatrx1 Deltatrx2 cells were
      60% that of wild-type cells. The data suggest that, in the absence of
      thioredoxin, cells cannot support the high rate of dNTP synthesis required for
      efficient DNA synthesis during S phase. The results constitute in vivo evidence
      for thioredoxin being a physiologically relevant electron donor for
      ribonucleotide reductase during DNA precursor synthesis.

PMID- 16574643
TI  - Interaction between RAX and PKR modulates the effect of ethanol on protein
      synthesis and survival of neurons.
AB  - Ethanol exposure inhibits protein synthesis and causes cell death in the
      developing central nervous system. The double-stranded RNA (dsRNA)-activated
      protein kinase (PKR), a serine/threonine protein kinase, plays an important role
      in translational regulation and cell survival. PKR has been well known for its
      anti-viral response. Upon activation by viral infection or dsRNA, PKR
      phosphorylates its substrate, the alpha-subunit of eukaryotic translation
      initiation factor-2 (eIF2alpha) leading to inhibition of translation initiation.
      It has recently been shown that, in the absence of a virus or dsRNA, PKR can be
      activated by direct interactions with its protein activators, PACT, or its mouse
      homologue, RAX. We have demonstrated that exposure to ethanol increased the
      phosphorylation of PKR and eIF2alpha in the developing cerebellum. The effect of
      ethanol on PKR/eIF2alpha phosphorylation positively correlated to the expression
      of PACT/RAX in cultured neuronal cells. Using PKR inhibitors and PKR null mouse
      fibroblasts, we verified that ethanol-induced eIF2alpha phosphorylation was
      mediated by PKR. Overexpression of a wild-type RAX dramatically enhanced
      sensitivity to ethanol-induced PKR/eIF2alpha phosphorylation, as well as
      translational inhibition and cell death. In contrast, overexpression of a mutant
      (S18A) RAX inhibited ethanol-mediated PKR/eIF2alpha activation. Ethanol promoted
      PKR and RAX association in cells expressing wild-type RAX but not in cells
      expressing S18A RAX. S18A RAX functioned as a dominant negative protein and
      blocked ethanol-induced inhibition of protein synthesis and cell death. Our
      results suggest that the interactions between PKR and PACT/RAX modulate the
      effect of ethanol on protein synthesis and cell survival in the central nervous
      system.

PMID- 16574644
TI  - Partnership of PGC-1alpha and HNF4alpha in the regulation of lipoprotein
      metabolism.
AB  - Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha)
      is a transcriptional coactivator involved in several aspects of energy
      metabolism. It is induced or activated under different stimuli in a highly tissue
      specific manner and subsequently partners with certain transcription factors in
      those tissues to execute various biological programs. In the fasted liver, PGC
      1alpha is induced and interacts with hepatocyte nuclear factor 4alpha (HNF4alpha)
      and other transcription factors to activate gluconeogenesis and increase hepatic
      glucose output. Given the broad spectrum of liver genes responsive to HNF4alpha,
      we sought to determine those that were specifically targeted by the combination
      of PGC-1alpha and HNF4alpha. Coexpression of these two molecules in murine stem
      cells reveals a high induction of mRNA for apolipoproteins A-IV and C-II. Forced
      expression of PGC-1alpha in mouse and human hepatoma cells increases the mRNA of
      a subset of apolipoproteins implicated in very low density lipoprotein and
      triglyceride metabolism, including apolipoproteins A-IV, C-II, and C-III.
      Coactivation of the apoC-III/A-IV promoter region by PGC-1alpha occurs through a
      highly conserved HNF4alpha response element, the loss of which completely
      abolishes activation by PGC-1alpha and HNF4alpha. Adenoviral infusion of PGC
      1alpha into live mice increases hepatic expression of apolipoproteins A-IV, C-II,
      and C-III and increases serum and very low density lipoprotein triglyceride
      levels. Conversely, knock down of PGC-1alpha in vivo causes a decrease in both
      apolipoprotein expression and serum triglyceride levels. These data point to a
      crucial role for the PGC-1alpha/HNF4alpha partnership in hepatic lipoprotein
      metabolism.

PMID- 16574645
TI  - Wild-type presenilin 1 protects against Alzheimer disease mutation-induced
      amyloid pathology.
AB  - Mutations in presenilin 1 (PS1) lead to dominant inheritance of early onset
      familial Alzheimer disease (FAD). These mutations are known to alter the gamma
      secretase cleavage of the amyloid precursor protein, resulting in increased ratio
      of Abeta42/Abeta40 and accelerated amyloid plaque pathology in transgenic mouse
      models. To investigate the factors that drive the Abeta42/Abeta40 ratio and
      amyloid pathogenesis and to investigate the possible interactions between wild
      type and FAD mutant PS1, which are co-expressed in transgenic animals, we
      expressed the PS1 M146V knock-in allele either on wild-type PS1 (PS1M146V/+) or
      PS1 null (PS1M146V/-) background and crossed these alleles with the Tg2576 APP
      transgenic mice. Introduction of the PS1 M146V mutation on Tg2576 background
      resulted in earlier onset of plaque pathology. Surprisingly, removing the wild
      type PS1 in the presence of the PS1 M146V mutation (PS1M146V/-) greatly
      exacerbated the amyloid burden; and this was attributed to a reduction of gamma
      secretase activity rather than an increase in Abeta42. Our findings establish a
      protective role of the wild-type PS1 against the FAD mutation-induced amyloid
      pathology through a partial loss-of-function mechanism.

PMID- 16574646
TI  - Pigment shuffling in antenna systems achieved by expressing prokaryotic
      chlorophyllide a oxygenase in Arabidopsis.
AB  - The organization of pigment molecules in photosystems is strictly determined. The
      peripheral antennae have both chlorophyll a and b, but the core antennae consist
      of only chlorophyll a in green plants. Furthermore, according to the recent model
      obtained from the crystal structure of light-harvesting chlorophyll a/b-protein
      complexes II (LHCII), individual chlorophyll-binding sites are occupied by either
      chlorophyll a or chlorophyll b. In this study, we succeeded in altering these
      pigment organizations by introducing a prokaryotic chlorophyll b synthesis gene
      (chlorophyllide a oxygenase (CAO)) into Arabidopsis. In these transgenic plants
      (Prochlirothrix hollandica CAO plants), approximately 40% of chlorophyll a of the
      core antenna complexes was replaced by chlorophyll b in both photosystems.
      Chlorophyll a/b ratios of LHCII also decreased from 1.3 to 0.8 in PhCAO plants.
      Surprisingly, these transgenic plants were capable of photosynthetic growth
      similar to wild type under low light conditions. These results indicate that
      chlorophyll organizations are not solely determined by the binding affinities,
      but they are also controlled by CAO. These data also suggest that strict
      organizations of chlorophyll molecules are not essential for photosynthesis under
      low light conditions.

PMID- 16574647
TI  - Attenuation of peroxisome proliferator-activated receptor gamma (PPARgamma)
      mediates gastrin-stimulated colorectal cancer cell proliferation.
AB  - Peroxisome proliferators-activated receptor gamma (PPARgamma) has been shown to
      suppress cell proliferation and tumorigenesis, whereas the gastrointestinal
      regulatory peptide gastrin stimulates the growth of neoplastic cells. The present
      studies were directed to determine whether changes in PPARgamma expression might
      mediate the effects of gastrin on the proliferation of colorectal cancer (CRC).
      Initially, using growth assays, we determined that the human CRC cell line DLD-1
      expressed both functional PPARgamma and gastrin receptors. Amidated gastrin (G
      17) attenuated the growth suppressing effects of PPARgamma by decreasing
      PPARgamma activity and total protein expression, in part through an increase in
      the rate of proteasomal degradation. G-17-induced degradation of PPARgamma
      appeared to be mediated through phosphorylation of PPARgamma at serine 84 by a
      process involving the biphasic phosphorylation of ERK1/2 and activation of the
      epidermal growth factor receptor (EGFR). These results were confirmed through the
      use of EGFR antagonist AG1478 and MEK1 inhibitor PD98059. Furthermore, mutation
      of PPARgamma at serine 84 reduced the effects of G-17, as evident by inability of
      G-17 to attenuate PPARgamma promoter activity, degrade PPARgamma, or inhibit the
      growth suppressing effects of PPARgamma. The results of these studies demonstrate
      that the trophic properties of gastrin in CRC may be mediated in part by
      transactivation of the EGFR and phosphorylation of ERK1/2, leading to degradation
      of PPARgamma protein and a decrease in PPARgamma activation.

PMID- 16574648
TI  - Protein-tyrosine phosphatase PCP-2 inhibits beta-catenin signaling and increases
      E-cadherin-dependent cell adhesion.
AB  - beta-Catenin is a key molecule involved in both cell adhesion and Wnt signaling
      pathway. However, the exact relationship between these two roles has not been
      clearly elucidated. Tyrosine phosphorylation of beta-catenin was shown to
      decrease its binding to E-cadherin, leading to decreased cell adhesion and
      increased beta-catenin signaling. We have previously shown that receptor-like
      protein-tyrosine phosphatase PCP-2 localizes to the adherens junctions and
      directly binds and dephosphorylates beta-catenin, suggesting that PCP-2 might
      regulate the balance between signaling and adhesive beta-catenin. Here we
      demonstrate that PCP-2 can inhibit both the wild-type and constitutively active
      forms of beta-catenin in activating target genes such as c-myc. The phosphatase
      activity of PCP-2 is required for this effect since loss of catalytic activity
      attenuates its inhibitory effect on beta-catenin activation. Expression of PCP-2
      in SW480 colon cancer cells can lead to stabilization of cytosolic pools of beta
      catenin perhaps, by virtue of their physical interaction. PCP-2 expression also
      leads to increased membrane-bound E-cadherin and greater stabilization of
      adherens junctions by dephosphorylation of beta-catenin, which could further
      sequester cytosolic beta-catenin and thus inhibit beta-catenin mediated nuclear
      signaling. Furthermore, SW480 cells stably expressing PCP-2 have a reduced
      ability to proliferate and migrate. Thus, PCP-2 may play an important role in the
      maintenance of epithelial integrity, and a loss of its regulatory function may be
      an alternative mechanism for activating beta-catenin signaling.

PMID- 16574649
TI  - Nitric oxide signaling via nuclearized endothelial nitric-oxide synthase
      modulates expression of the immediate early genes iNOS and mPGES-1.
AB  - Stimulation of freshly isolated rat hepatocytes with lysophosphatidic acid (LPA)
      resulted in LPA1 receptor-mediated and nitricoxide-dependent up-regulation of the
      immediate early genes iNOS (inducible nitric-oxide synthase (NOS)) and mPGES-1
      (microsomal prostaglandin E synthase-1). Because LPA is a ligand for both cell
      surface and intracellular receptor sites and a potent endothelial NOS (eNOS)
      activator, we hypothesized that NO derived from activated nuclearized eNOS might
      participate in gene regulation. Herein we show, by confocal microscopy performed
      on porcine cerebral endothelial cells expressing native LPA1-receptor and eNOS
      and on HTC4 rat hepatoma cells co-transfected with recombinant human LPA1
      receptor and fused eNOS-GFP cDNA, a dynamic eNOS translocation from peripheral to
      nuclear regions upon stimulation with LPA. Nuclear localization of eNOS and its
      downstream effector, soluble guanylate cyclase, were demonstrated in situ in rat
      liver specimens by immunogold labeling using specific antibodies. Stimulation of
      this nuclear fraction with LPA and the NO donor sodium nitroprusside resulted,
      respectively, in increased production of nitrite (and eNOS phosphorylation) and
      cGMP; these separate responses were also correspondingly blocked by NOS inhibitor
      L-NAME and soluble guanylate cyclase inhibitor ODQ. In addition, sodium
      nitroprusside evoked a sequential increase in nuclear Ca2+ transients, activation
      of p42 MAPK, NF-kappaB binding to DNA consensus sequence, and dependent iNOS RNA.
      This study describes a hitherto unrecognized molecular mechanism by which nuclear
      eNOS through ensuing NO modulates nuclear calcium homeostasis involved in gene
      transcription-associated events. Moreover, our findings strongly support the
      concept of the nucleus as an autonomous signaling compartment.

PMID- 16574650
TI  - Expression of vascular endothelial growth factor receptor 1 in bone marrow
      derived mesenchymal cells is dependent on hypoxia-inducible factor 1.
AB  - Bone marrow-derived cells are recruited to sites of ischemia, where they promote
      tissue vascularization. This response is dependent upon the expression of
      vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1), which mediates
      cell migration in response to VEGF or placental growth factor (PLGF). In this
      study, we found that exposure of cultured mouse bone marrow-derived mesenchymal
      stromal cells (MSC) to hypoxia or an adenovirus encoding a constitutively active
      form of hypoxia-inducible factor 1 (HIF-1) induced VEGFR1 mRNA and protein
      expression and promoted ex vivo migration in response to VEGF or PLGF. MSC in
      which HIF-1 activity was inhibited by a dominant negative or RNA interference
      approach expressed markedly reduced levels of VEGFR1 and failed to migrate or
      activate AKT in response to VEGF or PLGF. Thus, loss-of-function and gain-of
      function approaches demonstrated that HIF-1 activity is necessary and sufficient
      for basal and hypoxia-induced VEGFR1 expression in bone marrow-derived MSC.

PMID- 16574651
TI  - 9-cis-retinoic acid up-regulates expression of transcriptional coregulator PELP1,
      a novel coactivator of the retinoid X receptor alpha pathway.
AB  - Retinoid X receptor alpha (RXRalpha), functioning as either a homodimer or a
      heterodimer with peroxisome proliferator receptors, is known to be involved in
      manifesting antiproliferative effects in cells. Consequently, studies of RXRalpha
      functions and its coregulators have been in the focus for therapeutic approaches
      against cancer. Here we have discovered that 9-cis-retinoic acid (9-cis-RA), a
      RXRalpha-specific ligand, up-regulated the expression of transcriptional
      coregulatory protein PELP1 (proline-, glutamic acid-, and leucine-rich protein
      1). PELP1 functioned as a coactivator of RXRalpha, increasing its transactivation
      function in response to 9-cis-RA as evident by the retinoid X receptor response
      element-luciferase assays. PELP1 was found to be a binding partner of RXRalpha,
      and the binding interactions were confirmed both in vitro and in vivo. An
      electrophoretic mobility shift assay showed greater formation and stability of
      RXRalpha homodimers on consensus oligonucleotides in PELP1-overexpressing clones
      in comparison to the pcDNA clones. The presence of PELP1 in these oligonucleotide
      bound RXRalpha homodimers was proved by the supershift of the complex when
      incubated with PELP1-specific antibody. PELP1-overexpressing stable MCF-7 cells
      exhibited a significantly higher extent of 9-cis-RA-induced apoptosis than the
      control pcDNA clones. Silencing of PELP1 expression in parental MCF-7 cells and
      PELP1-overexpressing clones using PELP1-specific RNA-mediated interference
      compromised the susceptibility to 9-cis-RA-induced apoptosis. PELP1 could also
      function as a coactivator of the RXRalpha-peroxisome proliferator-activated
      receptor (PPARgamma) heterodimer as evident by the peroxisome proliferator
      activated receptor response element-luciferase assay in response to both 9-cis-RA
      and PPARgamma-specific ligands. This was reinforced by the higher propensity of
      PELP1-overexpressing clones to undergo differentiation in response to PPARgamma
      specific ligands. This study has revealed a novel facet of PELP1 functions and
      identified it to be an important potentiator of the antiproliferative effects of
      9-cis-RA and PPARgamma-specific ligands.

PMID- 16574652
TI  - Fine regulation of RhoA and Rock is required for skeletal muscle differentiation.
AB  - The RhoA GTPase controls a variety of cell functions such as cell motility, cell
      growth, and gene expression. Previous studies suggested that RhoA mediates
      signaling inputs that promote skeletal myogenic differentiation. We show here
      that levels and activity of RhoA protein are down-regulated in both primary avian
      myoblasts and mouse satellite cells undergoing differentiation, suggesting that a
      fine regulation of this GTPase is required. In addition, ectopic expression of
      activated RhoA in primary quail myocytes, but not in mouse myocytes, inhibits
      accumulation of muscle-specific proteins and cell fusion. By disrupting RhoA
      signaling with specific inhibitors, we have shown that this GTPase, although
      required for cell identity in proliferating myoblasts, is not essential for
      commitment to terminal differentiation and muscle gene expression. Ectopic
      expression of an activated form of its downstream effector, Rock, impairs
      differentiation of both avian and mouse myoblasts. Conversely, Rock inhibition
      with specific inhibitors and small interfering RNA-mediated gene silencing leads
      to accelerated progression in the lineage and enhanced cell fusion, underscoring
      a negative regulatory function of Rock in myogenesis. Finally, we have reported
      that Rock acts independently from RhoA in preventing myoblast exit from the cell
      cycle and commitment to differentiation and may receive signaling inputs from Raf
      1 kinase.

PMID- 16574653
TI  - CUTL1 is phosphorylated by protein kinase A, modulating its effects on cell
      proliferation and motility.
AB  - CUTL1, also known as CDP (CCAAT Displacement Protein), Cut, or Cux-1, is a
      homeodomain transcription factor known to play an essential role in development
      and cell cycle progression. Previously, we identified CUTL1 as modulator of cell
      motility and invasiveness. Here we report that protein kinase A (PKA), known to
      inhibit tumor progression in various tumor types, directly phosphorylates CUTL1
      at serine 1215 in NIH3T3 fibroblasts. The PKA-induced phosphorylation results in
      decreased DNA binding affinity of CUTL1 and diminished CUTL1-mediated cell cycle
      progression and cell motility. Furthermore, the expression of several CUTL1
      target genes involved in proliferation and migration, such as DNA polymerase A
      and DKK2, was modulated by PKA-induced phosphorylation. These data identify CUTL1
      as a novel target of PKA through which this protein kinase can modulate tumor
      cell motility and tumor progression.

PMID- 16574655
TI  - Subcellular targeting of RGS9-2 is controlled by multiple molecular determinants
      on its membrane anchor, R7BP.
AB  - RGS9-2, a member of the R7 regulators of G protein signaling (RGS) protein family
      of neuronal RGS, is a critical regulator of G protein signaling. In striatal
      neurons, RGS9-2 is tightly associated with a novel palmitoylated protein, R7BP
      (R7 family binding protein). Here we report that R7BP acts to target the
      localization of RGS9-2 to the plasma membrane. Examination of the subcellular
      distribution in native striatal neurons revealed that both R7BP and RGS9-2 are
      almost entirely associated with the neuronal membranes. In addition to the plasma
      membrane, a large portion of RGS9-2 was found in the neuronal specializations,
      the postsynaptic densities, where it forms complexes with R7BP and its
      constitutive partner Gbeta5. Using site-directed mutagenesis we found that the
      molecular determinants that specify the subcellular targeting of RGS9
      2.Gbeta5.R7BP complex are contained within the 21 C-terminal amino acids of R7BP.
      This function of the C terminus was found to require the synergistic
      contributions of its two distinct elements, a polybasic motif and palmitoylated
      cysteines, which when combined are sufficient for directing the intracellular
      localization of the constituent protein. In differentiated neurons, the C
      terminal targeting motif of R7BP was found to be essential for mediating its
      postsynaptic localization. In addition to the plasma membrane targeting elements,
      we identified two functional nuclear localization sequences that can mediate the
      import of R7BP into the nucleus upon depalmitoylation. These findings provide a
      mechanism for the subcellular targeting of RGS9-2 in neurons.

PMID- 16574654
TI  - NAB2 represses transcription by interacting with the CHD4 subunit of the
      nucleosome remodeling and deacetylase (NuRD) complex.
AB  - Early growth response (EGR) transactivators act as critical regulators of several
      physiological processes, including peripheral nerve myelination and progression
      of prostate cancer. The NAB1 and NAB2 (NGFI-A/EGR1-binding protein)
      transcriptional corepressors directly interact with three EGR family members
      (Egr1/NGFI-A/zif268, Egr2/Krox20, and Egr3) and repress activation of their
      target promoters. To understand the molecular mechanisms underlying NAB
      repression, we found that EGR activity is modulated by at least two repression
      domains within NAB2, one of which uniquely requires interaction with the CHD4
      (chromodomain helicase DNA-binding protein 4) subunit of the NuRD (nucleosome
      remodeling and deacetylase) chromatin remodeling complex. Both NAB proteins can
      bind either CHD3 or CHD4, indicating that the interaction is conserved among
      these two protein families. Furthermore, we show that repression of the
      endogenous Rad gene by NAB2 involves interaction with CHD4 and demonstrate
      colocalization of NAB2 and CHD4 on the Rad promoter in myelinating Schwann cells.
      Finally, we show that interaction with CHD4 is regulated by alternative splicing
      of the NAB2 mRNA.

PMID- 16574656
TI  - Evidence for assembly of small multidrug resistance proteins by a "two-faced"
      transmembrane helix.
AB  - Clinically significant bacterial resistance to drugs and cytotoxic compounds can
      be conferred by the energy-dependent efflux of toxicants, catalyzed by proteins
      embedded in the bacterial cell membrane. One such group of proteins, the small
      multidrug resistance family, are drug/proton antiporters that must oligomerize to
      function, a process that requires the assembly of at least two inactive monomers
      by intermolecular association of their four transmembrane helices. Here, we have
      used peptides that correspond to each of the four wild type transmembrane helices
      of the Halobacterium salinarum protein Hsmr and a corresponding library of mutant
      peptides to determine the interactive surfaces that likely contribute to protein
      oligomerization. Hsmr peptides were examined for strong (sodium dodecyl sulfate
      resistant) and weaker (perfluorooctanoate-resistant) helix-helix interactions, in
      conjunction with circular dichroism, fluorescence energy transfer measurements,
      and molecular modeling. The results are compatible with a scheme in which two
      faces of helix four permit self-assembly via a higher affinity asymmetric pairing
      and a lower affinity symmetric interaction, resulting in a discrete tetramer. Our
      finding that two surfaces of helix four can contribute to the stability of small
      multidrug resistance protein assembly provides a molecular basis for the design
      of therapeutics that target this antibiotic resistance mechanism.

PMID- 16574657
TI  - Specific regulation of IRS-2 expression by glucose in rat primary pancreatic
      islet beta-cells.
AB  - Insulin receptor substrate 2 (IRS-2) plays a critical role in pancreatic beta
      cells. Increased IRS-2 expression promotes beta-cell growth and survival, whereas
      decreased IRS-2 levels lead to apoptosis. It was found that IRS-2 turnover in rat
      islet beta-cells was rapid, with mRNA and protein half-lives of approximately 90
      min and approximately 2 h, respectively. However, this was countered by specific
      glucose-regulated IRS-2 expression mediated at the transcriptional level. Glucose
      (> or = 6 mM) increased IRS-2 mRNA and protein levels in a dose-dependent manner,
      reaching a maximum 4-fold increase in IRS-2 mRNA and a 5-6-fold increase in IRS-2
      protein levels at > or = 12 mM glucose (p < or = 0.01). Glucose (15 mM)
      regulation of islet beta-cell IRS-2 gene expression was rapid, with a significant
      increase in IRS-2 mRNA levels within 2 h that reached a maximum 4-fold increase
      by 4 h. IRS-2 protein expression in beta-cells followed that of IRS-2 mRNA.
      Glucose metabolism was necessary for increased IRS-2 expression in beta-cells.
      Moreover, inhibition of a glucose-induced rise in islet beta-cell cytosolic
      [Ca2+]i prevented an increase in IRS-2 expression, indicating this was Ca2+
      dependent. The glucose-induced rise in IRS-2 levels correlated with increased IRS
      2 tyrosine phosphorylation and downstream activation of protein kinase B. These
      data indicate that fluctuations of glucose in the normal physiological range (5
      15 mM) promote beta-cell survival via regulation of IRS-2 expression and a
      subsequent parallel protein kinase B activation. Given that the onset of type-2
      diabetes is marked by loss of beta-cells, these data further the idea that
      controlled IRS-2 expression in beta-cells could be a therapeutic means to promote
      beta-cell survival and delay the onset of the disease.

PMID- 16574658
TI  - Regulation of Aurora-A kinase gene expression via GABP recruitment of
      TRAP220/MED1.
AB  - The TRAP/Mediator coactivator complex serves as a functional interface between
      DNA-bound transactivators and the RNA polymerase II-associated basal
      transcription apparatus. TRAP220/MED1 is a variably associated subunit of the
      complex that plays a specialized role in selectively targeting TRAP/Mediator to
      specific genes. Ablation of the Trap220/Med1 gene in mice impairs embryonic cell
      growth, yet the underlying mechanism is unknown. In this report, we identified
      distinct cell growth regulatory genes whose expression is affected by the loss of
      TRAP220/MED1 by RNA interference. Among the down-regulated genes revealed by cDNA
      microarray analyses, we identified Aurora-A, a centrosome kinase that plays a
      critical role in regulating M phase events and is frequently amplified in several
      types of cancer. In general, we found that TRAP220/MED1 expression is required
      for high basal levels of Aurora-A gene expression and that ectopic overexpression
      of TRAP220/MED1 coactivates transcription from the Aurora-A gene promoter.
      Furthermore, chromatin immunoprecipitation assays show that TRAP220/MED1
      containing TRAP/Mediator complexes directly bind to the Aurora-A promoter in
      vivo. Finally, we present evidence suggesting that TRAP/Mediator is recruited to
      the Aurora-A gene via direct interactions between TRAP220/MED1 and the Ets
      related transcription factor GABP. Taken together, these findings suggest that
      TRAP220/MED1 plays a novel coregulatory role in facilitating the recruitment of
      TRAP/Mediator to specific target genes involved in growth and cell cycle
      progression.

PMID- 16574659
TI  - Aspartyl-tRNA synthetase is the target of peptide nucleotide antibiotic Microcin
      C.
AB  - Microcin C is a ribosome-synthesized heptapeptide that contains a modified
      adenosine monophosphate covalently attached to the C-terminal aspartate. Microcin
      C is a potent inhibitor of bacterial cell growth. Based on the in vivo kinetics
      of inhibition of macromolecular synthesis, Microcin C targets translation,
      through a mechanism that remained undefined. Here, we show that Microcin C is a
      subject of specific degradation inside the sensitive cell. The product of
      degradation, a modified aspartyl-adenylate containing an N-acylphosphoramidate
      linkage, strongly inhibits translation by blocking the function of aspartyl-tRNA
      synthetase.

PMID- 16574660
TI  - Clathrin-mediated endocytosis of the epithelial sodium channel. Role of epsin.
AB  - Here we present evidence that the epithelial sodium channel (ENaC), a heteromeric
      membrane protein whose surface expression is regulated by ubiquitination, is
      present in clathrin-coated vesicles in epithelial cells that natively express
      ENaC. The channel subunits are ubiquitinated and co-immunoprecipitate with both
      epsin and clathrin adaptor proteins, and epsin, as expected, co
      immunoprecipitates with clathrin adaptor proteins. The functional significance of
      these interactions was evaluated in a Xenopus oocyte expression system where co
      expression of epsin and ENaC resulted in a down-regulation of ENaC activity;
      conversely, co-expression of epsin sub-domains acted as dominant-negative
      effectors and stimulated ENaC activity. These results identify epsin as an
      accessory protein linking ENaC to the clathrin-based endocytic machinery thereby
      regulating the activity of this ion channel at the cell surface.

PMID- 16574661
TI  - Interaction of N-WASP with hnRNPK and its role in filopodia formation and cell
      spreading.
AB  - N-WASP is a member of the WASP family of proteins, which play essential roles in
      actin dynamics during cell adhesion and migration. hnRNPK is a member of the
      heterogeneous nuclear ribonucleoprotein complex, which has also been implicated
      in the regulation of cell spreading. Here, we identify a direct interaction
      between N-WASP and hnRNPK. We show that this interaction is mediated by the N
      terminal WH1 domain of N-WASP and the segment of hnRNPK containing its K
      interaction (KI) domain. Furthermore, these two proteins are co-localized at the
      cell periphery in the spreading initiation center during the early stage of cell
      spreading. We found that co-expression of hnRNPK with N-WASP reverses the
      stimulation of cell spreading by N-WASP, and this effect is correlated with
      hnRNPK binding to N-WASP. Expression of hnRNPK does not affect subcellular
      localization of N-WASP protein. However, co-expression of hnRNPK with N-WASP
      reduced filopodia formation stimulated by N-WASP in spreading cells. Together,
      these results identify hnRNPK as a new negative regulator of N-WASP and suggest
      that hnRNPK may regulate the initial stage of cell spreading by direct
      association with N-WASP in the spreading initiation center.

PMID- 16574662
TI  - Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase.
AB  - Rho-associated coiled-coil protein kinase (ROCK) is an effector for the small
      GTPase Rho and plays a pivotal role in diverse cellular activities, including
      cell adhesion, cytokinesis, and gene expression, primarily through an alteration
      of actin cytoskeleton dynamics. Here, we show that ROCK2 is localized in the
      nucleus and associates with p300 acetyltransferase both in vitro and in cells.
      Nuclear ROCK2 is present in a large protein complex and partially cofractionates
      with p300 by gel filtration analysis. By immunofluorescence, ROCK2 partially
      colocalizes with p300 in distinct insoluble nuclear structures. ROCK2
      phosphorylates p300 in vitro, and nuclear-restricted expression of constitutively
      active ROCK2 induces p300 phosphorylation in cells. p300 acetyltransferase
      activity is dependent on its phosphorylation status in cells, and p300
      phosphorylation by ROCK2 results in an increase in its acetyltransferase activity
      in vitro. These observations suggest that nucleus-localized ROCK2 targets p300
      for phosphorylation to regulate its acetyltransferase activity.

PMID- 16574663
TI  - Syndecan-2 is expressed in the microvasculature of gliomas and regulates
      angiogenic processes in microvascular endothelial cells.
AB  - Angiogenesis is the formation of new blood vessels from the existing vasculature
      and is necessary for tumor growth. Syndecan-2 (S2) is highly expressed in the
      microvasculature of mouse gliomas. When S2 expression was down-regulated in mouse
      brain microvascular endothelial cells (MvEC), this inhibited cell motility and
      reduced the formation of capillary tube-like structures in vitro. Pro-angiogenic
      growth factors and enzymes up-regulated during glioma tumorigenesis stimulated
      shedding of the S2 ectodomain from endothelial cells in vitro. The effect of shed
      S2 on angiogenic processes was investigated by incorporating recombinant S2
      ectodomain (S2ED) into in vitro angiogenesis assays. S2ED promoted membrane
      protrusion, migration, capillary tube formation, and cell-cell interactions. We
      therefore propose that S2 is necessary for angiogenesis of MvEC, proangiogenic
      factors expressed during glioma progression regulate S2 shedding, and shed S2
      ectodomain may increase endothelial cell angiogenic processes.

PMID- 16574664
TI  - Effects of a GTP-insensitive mutation of glutamate dehydrogenase on insulin
      secretion in transgenic mice.
AB  - Glutamate dehydrogenase (GDH) plays an important role in insulin secretion as
      evidenced in children by gain of function mutations of this enzyme that cause a
      hyperinsulinism-hyperammonemia syndrome (GDH-HI) and sensitize beta-cells to
      leucine stimulation. GDH transgenic mice were generated to express the human GDH
      HI H454Y mutation and human wild-type GDH in islets driven by the rat insulin
      promoter. H454Y transgene expression was confirmed by increased GDH enzyme
      activity in islets and decreased sensitivity to GTP inhibition. The H454Y GDH
      transgenic mice had hypoglycemia with normal growth rates. H454Y GDH transgenic
      islets were more sensitive to leucine- and glutamine-stimulated insulin secretion
      but had decreased response to glucose stimulation. The fluxes via GDH and
      glutaminase were measured by tracing 15N flux from [2-15N]glutamine. The H454Y
      transgene in islets had higher insulin secretion in response to glutamine alone
      and had 2-fold greater GDH flux. High glucose inhibited both glutaminase and GDH
      flux, and leucine could not override this inhibition. 15NH4Cl tracing studies
      showed 15N was not incorporated into glutamate in either H454Y transgenic or
      normal islets. In conclusion, we generated a GDH-HI disease mouse model that has
      a hypoglycemia phenotype and confirmed that the mutation of H454Y is disease
      causing. Stimulation of insulin release by the H454Y GDH mutation or by leucine
      activation is associated with increased oxidative deamination of glutamate via
      GDH. This study suggests that GDH functions predominantly in the direction of
      glutamate oxidation rather than glutamate synthesis in mouse islets and that this
      flux is tightly controlled by glucose.

PMID- 16574665
TI  - Vinblastine-induced apoptosis is mediated by discrete alterations in subcellular
      location, oligomeric structure, and activation status of specific Bcl-2 family
      members.
AB  - To gain a broader insight into the role of Bcl-2 proteins in apoptosis induced
      after mitotic arrest, we investigated the subcellular location, oligomeric
      structure, and protein interactions of Bax, Bcl-2, and Bcl-xL in vinblastine
      treated KB-3 cells. Vinblastine induced the translocation of Bax from the cytosol
      to the mitochondria, which was accompanied by conformational activation and
      oligomerization of Bax. Bcl-2 was located in the mitochondria, underwent
      multisite phosphorylation after vinblastine treatment, and was strictly monomeric
      under all conditions. In contrast, in control cells, Bcl-xL existed in both
      monomeric (30 kDa) and oligomeric (150 kDa) forms. Treatment with agents that
      induced Bcl-xL phosphorylation (microtubule inhibitors) caused loss of the 150
      kDa form, but this species was unaffected by apoptotic stimuli that did not
      stimulate phosphorylation. Vinblastine also promoted Bax activation and Bax
      oligomerization in HCT116 colon cancer cells. Both wild-type and Bax-deficient
      HCT116 cells expressed the 150-kDa form of Bcl-xL, which was depleted similarly
      in both cell lines upon vinblastine treatment. Co-immunoprecipitation studies
      revealed that in untreated KB-3 cells inactive cytosolic Bax interacted with Bcl
      xL, whereas in vinblastine-treated cells, activated mitochondrial Bax did not
      interact with Bcl-xL. Interaction of Bcl-2 with Bax was not observed under any
      condition. Overexpression of Bcl-xL inhibited vinblastine-induced Bax activation
      and Bax dimerization and in parallel inhibited apoptosis. The results indicate
      that vinblastine-induced apoptosis requires translocation, activation, and
      oligomerization of Bax and is associated with specific changes in the oligomeric
      properties of Bcl-xL, which occur independently of Bax.

PMID- 16574666
TI  - Is elective caesarian section really essential for prevention of mother to child
      transmission of HIV in the era of antiretroviral therapy and abstinence of breast
      feeding?
AB  - AIM: To determine whether vaginal delivery along with antiretroviral therapy and
      avoidance of breast feeding is safe in preventing mother to child transmission
      (MTCT) of HIV. SETTING: Pediatric & Perinatal HIV clinic, B.J. Wadia Hospital for
      children, Mumbai. STUDY DESIGN: Retrospective analysis. METHODS AND MATERIALS:
      222 HIV-infected pregnant women were treated with zidovudine from 14 weeks of
      gestation onwards. 174 women underwent an elective caesarian section whereas 48
      women delivered spontaneously vaginally. All infants were treated with zidovudine
      for 6 weeks and breast feeding was withheld. The HIV status of infants was
      determined at 18 months by ELISA test. RESULTS: Of the 174 infants delivered
      through LSCS delivery, two were HIV infected whereas 172 (98.9%) were HIV
      uninfected. Of the 48 infants delivered vaginally, 47 (97.9%) were HIV negative
      and one child was HIV infected. Thus, elective caesarean section was not
      statistically better as compared to vaginal delivery (p = 0.8696) suggesting that
      vaginal delivery was as effective as caesarean section for prevention of MTCT of
      HIV when added with antiretroviral therapy and no breast feeding. CONCLUSION:
      Vaginal delivery along with antiretroviral therapy in mother and baby and
      avoidance of breast feeding is equivalent to that of an elective LSCS delivery
      for prevention of mother-to-child transmission of HIV. Surgical intervention may
      thus not be required in these women.

PMID- 16574667
TI  - Perforin and Fas induced by IFNgamma and TNFalpha mediate beta cell death by OT-I
      CTL.
AB  - Direct interaction between auto-reactive CTL and specific peptide-MHC class I
      complexes on pancreatic beta cells is critical in mediating beta cell destruction
      in type I diabetes. We used mice with genetic modifications in three major
      pathways used by CTL, perforin, Fas and pro-inflammatory cytokines to assess the
      relative contribution of these mechanisms to beta cell death. In vitro-activated
      ovalbumin (OVA)-specific CTL, from OT-I TCR-transgenic mice, specifically killed
      transgenic beta cells expressing OVA (from RIP-mOVA mice) in a 16-h cytotoxicity
      assay. Perforin-deficient CTL had a reduced ability to kill OVA-expressing islets
      in vitro (22.1 +/- 3.8%) compared with wild-type CTL (71.4 +/- 4.6%). Fas
      deficient islets were only slightly protected from wild-type CTL but were
      completely protected from the residual killing observed with perforin-deficient
      CTL. Residual cytotoxicity in perforin-deficient CTL was also prevented by
      overexpression of SOCS-1, which blocks multiple cytokine signaling pathways. It
      was also prevented by pre-incubation with anti-tumor necrosis factor-alpha (anti
      TNFalpha) antibody or by blocking IFNgamma responsiveness through expressing a
      dominant negative IFNgamma receptor. Perforin-deficient CTL produced IFNgamma and
      TNFalpha that was shown to directly induce islet Fas expression during the
      assays. This suggests that Fas-deficiency, SOCS-1 overexpression and blockade of
      IFNgamma and TNFalpha all protect beta cells from residual cytotoxicity of
      perforin-deficient CTL by blocking Fas upregulation. These findings indicate that
      wild-type CTL destroy antigen-expressing islets via a perforin-dependent
      mechanism. However, in the absence of perforin, the Fas/FasL pathway provides an
      alternative mechanism dependent on islet cell Fas upregulation by cytokines
      IFNgamma and TNFalpha.

PMID- 16574668
TI  - Reactivity of naive CD4+CD25- T cells against gut microflora in healthy mice.
AB  - We have previously shown that conventional as well as germ-free CD4+ T cells
      depleted of CD25+ cells from the gut-associated lymphoid tissue and the periphery
      proliferate specifically in response to enterobacterial antigen exposure whereas
      unfractionated CD4+ T cells are not reactive under these conditions. Here we show
      that the majority of the enteroantigen-specific CD4+ CD25- T cells are naive
      cells expressing a CD45RB high, CD62L high and CD44 low phenotype. These cells
      are also present in the thymus and data from adult thymectomized mice show that
      they represent late (>6 weeks) thymic emigrants. Upon enteroantigen activation,
      the CD4+ CD25- T cells secrete IL-4, IL-5, IL-10, granulocyte macrophage colony
      stimulating factor, tumor necrosis factor-alpha and IFN-gamma. Clonotype mapping
      of the TCRBV regions 1-18 of enteroantigen-reactive CD4+ CD25- T cells by TCR
      clonotype mapping revealed the polyclonal nature of this subset. In conclusion,
      we have for the first time demonstrated the presence of an evolutionary,
      functionally conserved subset of CD4+ T cells, which are reactive against
      enterobacterial antigens. This subset resides both in the thymus and the
      periphery; it is not dependent on previous antigen experience and represents late
      thymic emigrants, which by enteroantigen-induced activation express a mixed Th 1
      Th 2 phenotype. At homeostatic conditions, CD25+ T cells maintain peripheral
      tolerance in this CD4+ T cell subset.

PMID- 16574669
TI  - Francisella tularensis LPS induces the production of cytokines in human monocytes
      and signals via Toll-like receptor 4 with much lower potency than E. coli LPS.
AB  - Francisella tularensis is a virulent Gram-negative intracellular pathogen. To
      address the signaling routes involved in the response of host cells to LPS from
      F. tularensis live vaccine strain (LVS), experiments were performed in
      transiently transfected 293 cells. Induction of kappaB-driven transcriptional
      activity by 2.5 mug ml(-1) F. tularensis LPS isolated by phenol-water and ether
      water extraction, was observed in cells transfected with Toll-like receptor (TLR)
      4 and MD-2, although CD14 was required for optimal induction. Conversely, TLR2,
      TLR2/TLR1 or TLR2/TLR6 transfected cells did not show kappaB-driven
      transcriptional activity in the presence of F. tularensis LPS. In human monocytic
      cells, F. tularensis LPS activated extracellular signal-regulated kinases and the
      production of pro-inflammatory proteins. Concentrations of 5-10 mug ml(-1) F.
      tularensis LPS elicited a similar pattern of mRNA and protein induction than 0.1
      mug ml(-1) E. coli LPS, including the expression of CXC chemokines (IL-8, Gro and
      IFN-gamma-inducible protein-10); CC chemokines (monocyte chemoattractant protein
      1 and -2, macrophage-derived chemoattractant, macrophage inflammatory protein
      1alpha and -1beta and RANTES (regulated upon activation, normal T cell expressed
      and secreted) and pro-inflammatory cytokines (IL-6 and tumor necrosis factor
      alpha). Altogether, these data indicate that LPS from F. tularensis LVS signals
      via TLR4 at higher concentrations than those required for E. coli LPS, which may
      explain the inflammatory reaction and the low endotoxic response associated to
      vaccination with LVS in humans.

PMID- 16574670
TI  - Requirement of high-affinity IL-2-IL-2R interaction for T cell anergy induction.
AB  - Incomplete T cell antigen receptor-mediated signaling induces an unresponsive
      state known as anergy. Previously, we had shown that anergy can be induced in
      antigen-primed but not naive T cells. In this report, we found that in vitro
      primed T cells from IL-2R alpha-deficient mice were resistant to anergy induction
      in contrast to comparably treated wild-type T cells. This resistance persisted
      even after proliferation of IL-2R alpha chain-deficient CD4 T cells with high
      dose IL-2-IL-2R beta gamma chains interaction. Thus, antigen activation, and/or
      progression through cell cycle are not sufficient to induce anergy susceptibility
      in T cells. The high-affinity IL-2-IL-2R interaction appears to play a critical
      role in this process.

PMID- 16574671
TI  - Single nucleotide polymorphisms of follicle-stimulating hormone receptor are
      associated with ovarian cancer susceptibility.
AB  - Epidemiological studies suggested that ovulation was associated with ovarian
      carcinogenesis. Follicle-stimulating hormone (FSH) played an important role in
      follicular development and was recently found to affect growth of ovarian
      epithelial cells. Single nucleotide polymorphisms (SNPs) Thr307Ala and Asn680Ser
      were two non-synonymous variations in the coding region of the FSH receptor
      (FSHR) gene. This hitherto first case-control study investigating the association
      between these two FSHR SNPs and the risk of ovarian cancer involved 202
      histopathologically confirmed ovarian cancer patients and 266 age-matched cancer
      free control subjects using restriction fragment length polymorphism assay and
      direct sequencing. Our results demonstrated that the 307Ala and 680Ser carriers
      were associated with significantly increased risk of developing serous and
      mucinous types of ovarian cancers (P < 0.0005, OR = 2.60, 95% CI = 1.56-4.34; and
      P < 0.0005, OR = 2.89, 95% CI = 1.73-4.84, adjusted for age, respectively) but
      not endometrioid and clear cell types. The two SNPs were found to be in modest
      linkage disequilibrium, D' = 0.804 and 0.701, r2 = 0.581 and 0.406 for the cancer
      and control groups, respectively. The major haplotype of 307Ala-680Ser was also
      associated with higher cancer risk (P = 0.033, OR = 1.39, 95% CI = 1.03-1.88),
      especially for the serous and mucinous carcinomas (P = 0.001, OR = 1.82, 95% CI =
      1.27-2.60). Our results suggested that the two FSHR SNPs might affect the
      susceptibility of women to specific subtypes of ovarian cancer. Different types
      of ovarian cancer might adopt distinct carcinogenetic pathways. Such
      understanding may be important in selecting patients for ovulation induction
      therapy.

PMID- 16574672
TI  - Patient attitudes towards self-report and biomarker alcohol screening by primary
      care physicians.
AB  - AIMS: One of the many barriers to more frequent alcohol screening by primary care
      physicians is a reported concern that patients may be offended by questions about
      drinking. However, evidence suggests that patients do not object to alcohol
      screening and actually expect physicians to ask about lifestyle factors that
      influence their health. The aim of this study was to provide more detailed
      information on patient attitudes toward self-report and biomarker alcohol
      screening and to explore whether demographic variables were related to these
      attitudes. METHODS: We administered (i) a survey about attitudes towards alcohol
      screening, and (ii) the Alcohol Use Disorders Identification Test-C (AUDIT-C) to
      primary care outpatients at the time of their medical appointments. The survey
      contained 10 items on patient opinions about being screened for at-risk drinking
      by physicians. Participants rated their levels of agreement with each statement
      using a 5-point Likert scale. Participants also provided demographic information.
      RESULTS: The majority of patients reported that they were supportive of physician
      screening about alcohol use. Responses on 3 of the 10 statements were related to
      patient race, age, and/or AUDIT-C results. CONCLUSIONS: In general, results
      support the fact that patients are in favour of being screened for at-risk
      drinking by their physicians whether the screening instrument was a self-report
      measure or an alcohol biomarker laboratory test. In addition, the majority of
      patients are open to advice from physicians about their alcohol use.

PMID- 16574673
TI  - Fenugreek (Trigonella foenum graecum) seed extract prevents ethanol-induced
      toxicity and apoptosis in Chang liver cells.
AB  - The protective effect of a polyphenolic extract of fenugreek seeds (FPEt) against
      ethanol (EtOH)-induced toxicity was investigated in human Chang liver cells.
      Cells were incubated with either 30 mM EtOH alone or together in the presence of
      seed extract for 24 h. Assays were performed in treated cells to evaluate the
      ability of seeds to prevent the toxic effects of EtOH. EtOH treatment suppressed
      the growth of Chang liver cells and induced cytotoxicity, oxygen radical
      formation and mitochondrial dysfunction. Reduced glutathione (GSH) concentration
      was decreased significantly (P < 0.05) while oxidized glutathione (GSSG)
      concentration was significantly elevated in EtOH-treated cells as compared with
      normal cells. Incubation of FPEt along with EtOH significantly increased cell
      viability in a dose-dependent manner, caused a reduction in lactate dehydrogenase
      leakage and normalized GSH/GSSG ratio. The extract dose-dependently reduced
      thiobarbituric acid reactive substances formation. Apoptosis was observed in EtOH
      treated cells while FPEt reduced apoptosis by decreasing the accumulation of sub
      G1 phase cells. The cytoprotective effects of FPEt were comparable with those of
      a positive control silymarin, a known hepatoprotective agent. The findings
      suggest that the polyphenolic compounds of fenugreek seeds can be considered
      cytoprotective during EtOH-induced liver damage.

PMID- 16574674
TI  - The pleiotropic effect of statins in haemodialysis patients is not the
      consequence of an inhibition of LDL oxidation by myeloperoxidase.

PMID- 16574675
TI  - A Crry for polar shedding.

PMID- 16574676
TI  - Necrotizing mastitis caused by calciphylaxis.

PMID- 16574677
TI  - Switching immunosuppression medications after renal transplantation--a common
      practice.
AB  - BACKGROUND: The rate of change to immunosuppression discharge regimens over time
      is unknown. We examined the frequency of changes to initial drug treatment
      regimens and factors associated with a drug change following renal
      transplantation. METHODS: Scientific Registry of Transplant Recipients data from
      adult recipients who underwent primary renal transplantation between January 1998
      and December 2002 were analysed. The Kaplan-Meier analysis was used to determine
      the frequency of regimen changes for the most common immunosuppression discharge
      regimens, type of change, and to examine switching between the calcineurin
      inhibitors tacrolimus (Tacro) and ciclosporin United States Pharmacopera (USP)
      modified (CsA). Cox proportional hazard regression was used to examine recipient,
      donor and transplant characteristics associated with a drug change. RESULTS: The
      majority of patients experienced a change to their discharge regimen post
      transplantation, and more changes were observed within higher-risk sub-groups of
      patients. Switching from CsA to Tacro was more common than Tacro to CsA.
      Significant factors associated with a drug change included those associated with
      graft loss. CONCLUSIONS: Significant immunosuppression regimen changes occur
      during the first 4 years post-transplantation. It is possible that early graft
      survival benefits proven in prospective clinical trials may not translate into
      long-term success in clinical practice, possibly in part because efficacious
      regimens are not necessarily maintained long-term.

PMID- 16574678
TI  - Steroid-free immunosuppression after renal transplantation-long-term experience
      from a single centre.
AB  - BACKGROUND: A steroid-free immunosuppressive protocol may improve the general
      well-being of patients, but long-term renal graft survival has been a concern.
      METHODS: In a retrospective clinical study, 329 consecutive transplantations with
      renal grafts at our centre during the period 1995-2004, were followed for up to
      9.3 years. Patients mainly received steroid-free immunosuppression with an
      initial induction with antithymocyte globulin or basiliximab and maintenance
      therapy with ciclosporin and mycophenolate mofetil (MMF). Steroids were given
      after rejection, or if the physician judged it necessary, for instance because of
      primary kidney disease or when calcineurin inhibitor toxicity was suspected.
      RESULTS: About 71% of the patients did not take steroids at all. Nevertheless,
      graft survival rates at 1, 5 and 7 years were 95, 77 and 72% for all grafts,
      including 27% living donor transplants and 27% second or subsequent grafts. Ten
      patients (3.2%) died with functioning grafts. Within the first year of
      transplantation there were 69 acute rejections in 63 patients (19%). Four cases
      (1.3%) of post-transplant lymphoproliferative disorder (PTLD) occurred with one
      graft loss and no deaths. Owing to a high PTLD rate in a previous patient cohort,
      total immunosuppression was lessened after 1998. CONCLUSIONS: Steroid avoidance
      is possible with good results with respect to acute rejection and long-term graft
      survival. After introducing MMF, largely avoiding muromonab-CD3 mouse raised
      monoclonal antibody against CD (OKT3), and reducing doses of calcineurin
      inhibitor, the rates of PTLD did not differ from what is usually found. For the
      present, induction and use of MMF, together with a calcineurin inhibitor, is
      probably to be preferred.

PMID- 16574679
TI  - Compromise of renal transplant blood flow by an arteriovenous graft.

PMID- 16574680
TI  - Acute myocardial infarction in thrombotic microangiopathies--clinical
      characteristics, risk factors and outcome.
AB  - BACKGROUND: Acute myocardial infarction (AMI) has been reported and is associated
      with poor outcome in the course of thrombotic microangiopathies (TMA). However,
      data are very limited in regard to the clinical characteristics, risk factors and
      outcome of AMI during TMA. Furthermore, current AMI definitions based on
      troponins are more sensitive and specific to detect myocardial injury. METHODS:
      We retrospectively analysed 74 consecutive patients with 78 TMA episodes. TMA was
      defined as platelets below 150 x 10(9)/l, haemolytic anaemia, elevated lactate
      dehydrogenase (LDH) and increased red cell fragmentation, and AMI as serum
      troponin I above 1 ng/ml with symptoms of myocardial ischaemia and/or appropriate
      electrocardiography (ECG) alterations. RESULTS: AMI occurred in 14 TMA episodes
      (18%) (9 non- and 5 ST-segment elevation AMI). AMI occurred 5+/-3 days after TMA
      diagnosis, predominately in clinically suspected thrombotic thrombocytopenic
      purpura (TTP) as TMA subtype. Independent risk factors for subsequent AMI were
      TTP (RR 2.2; 95% CI 1.1-5.6), and serum LDH above 1,000 U/l (RR 2.7; 95% CI 1.3
      7.2) as well as serum troponin I above 0.20 ng/ml at TMA presentation (RR 13.5;
      95% CI 2.6-86.8). LDH above 1,000 U/l together with troponin I above 0.20 ng/ml
      had a sensitivity of 86% (95% CI 60-96%) and a specificity of 95% (95% CI 86-98%)
      to predict AMI in the later course of TMA. AMI contributed substantially to
      morbidity causing left ventricular dysfunction in three of eight survivors and
      potentially accounted for the death in five of six non-survivors. CONCLUSIONS:
      AMI is an early, frequent and severe complication during TMA. AMI occurs
      especially in TTP, and serum LDH above 1,000 U/l in combination with serum
      troponin I above 0.20 ng/ml at TMA presentation are excellent predictors of
      subsequent AMI.

PMID- 16574681
TI  - Coeliac disease and risk of renal disease-a general population cohort study.
AB  - BACKGROUND: Coeliac disease (CD) may be a risk factor for renal disease. METHODS:
      We investigated the risk of any form of glomerulonephritis (GN) (acute, chronic
      and non-specified), chronic glomerulonephritis (CGN) and renal replacement
      therapy including dialysis treatment and kidney transplantation (KT) in patients
      with CD in a general population-based cohort study. We used Cox regression to
      assess the risk of renal disease in 14,336 patients who had received a diagnosis
      of CD (1964-2003) and 69,875 reference individuals matched for age, calendar
      year, sex and county. Patients were identified using the Swedish Hospital
      Discharge Registry. Follow-up began 1 year after study entry. RESULTS: CD was
      associated with an increased risk of any form of GN (hazard ratio (HR) = 1.64;
      95% confidence intervals (CI) = 1.01-2.66; P = 0.046; 89 events), CGN (HR = 2.65;
      95% CI = 1.34-5.24; P = 0.005; 39 events), dialysis (HR = 3.48; 95% CI = 2.26
      5.37; P < 0.001; 102 positive events) and KT (HR = 3.15; 95% CI = 1.29-7.71; P =
      0.012; 22 events). CONCLUSION: We suggest that immune characteristics associated
      with CD increase the risk of chronic renal disease. Individuals with CD may also
      be at a moderately increased risk of any form of GN.

PMID- 16574682
TI  - Fibronectin in blood invokes the development of focal segmental
      glomerulosclerosis in mouse model.
AB  - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is caused by gradual
      deposition of extracellular matrix proteins, one of which, fibronectin (FN) is
      critical for sclerosis development. The origin of the FN deposited at an early
      stage of FSGS is still unclear. METHODS: For investigating the origin of FN, the
      onset of increases in FN levels in the serum, glomeruli and urine were studied in
      a mouse model induced by adriamycin and compared with the time-course of
      development of glomerulosclerosis and expression of FN mRNA. RESULTS: In the FSGS
      mice, serum FN levels were significantly increased as early as the onset of
      proteinuria on day 4 (7.26 +/- 0.37 mg/ml compared with 5.58 +/- 0.76 mg/ml in
      normal controls, P < 0.05). This was followed by an increase in glomerular
      deposition of FN protein on day 7 (FN/actin ratio, 0.216 +/- 0.003 compared with
      0.039 +/- 0.009 in normal controls, P < 0.05). Glomerular m-RNA expression was
      also significantly elevated on day 7, but the locally synthesized FN did not show
      any increase until day 15. A significant increase in urinary FN protein and focal
      glomerulosclerosis was seen on day 11. CONCLUSIONS: We infer that FN in blood
      acts as an initiator of the development of FSGS in this mouse model. In addition,
      serum and urine FN proteins could serve as useful biomarkers for monitoring the
      progression of FSGS.

PMID- 16574683
TI  - Early markers of inflammation in a high angiotensin II state--results of studies
      in Bartter's/Gitelman's syndromes.
AB  - BACKGROUND: Inflammation has been increasingly recognized as playing a critical
      role in hypertension and atherosclerosis as reflected by overexpression and
      increased production of a variety of pro-inflammatory mediators. As angiotensin
      II (Ang II) also plays a major role in these diseases, the relationship between
      inflammation and Ang II has drawn increasing scrutiny. This study explores Ang II
      effects in Bartter's and Gitelman's syndromes (BS/GS) which do not develop
      hypertension and related cardiovascular remodelling and atherosclerosis, in spite
      of high Ang II levels and activation of the renin-angiotensin-aldosterone system
      while the NO system is up-regulated. METHODS: We evaluated the plasma levels of
      inflammation-associated markers, C-reactive protein (CRP), serum amyloid A (SAA),
      vascular cell adhesion molecules (VCAM) and intercellular adhesion molecules
      (ICAM), and the inflammation-related cytokines interleukin-6 (IL-6) and tumour
      necrosis factor-alpha (TNF-alpha) using immunonephelometric and ELISA-based
      assays. RESULTS: The study demonstrated that all markers of inflammation except
      TNF-alpha, were unchanged in BS/GS (2.51+/-0.62 mg/l in BS/GS vs 1.7+/-0.6 in
      controls for CRP; 4.56+/-1.09 mg/l in BS/GS vs 4.51+/-1.0 for SAA; 1.84+/-0.27
      ng/l in BS/GS vs 2.1+/-0.3 for IL-6; 449+/-83 ng/ml in BS/GS vs 410+/-92 for VCAM
      and 234+/-26 ng/ml in BS/GS vs 185+/-22 for ICAM), while TNF-alpha was increased
      (10.5+/-2.03 vs 3.68+/-0.2, P = 0.0001). CONCLUSIONS: The results of this study
      stress the critical role played by Ang II in controlling vascular biology
      including inflammation-related processes as well as highlighting the utility of
      BS/GS in investigating these pathways.

PMID- 16574684
TI  - Effects of bisphosphonates on bone loss in the first year after renal
      transplantation--a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Bone loss remains a serious problem after kidney transplantation and
      is most pronounced during the first months after engraftment. Bisphosphonates are
      frequently used to treat post-transplant osteodystrophy, but data of large
      randomized controlled trials (RCTs) are missing. METHODS: We, therefore,
      conducted this systematic review of the literature, searching electronic
      databases, reference lists and abstracts from scientific meetings to identify
      RCTs in all languages. The primary outcome assessed was the change in bone
      mineral density (BMD) during the early post-transplantation period. Based on the
      mean BMD change presented in the identified publications, the authors were asked
      for the individual BMD results of all randomized patients, determined at lumbar
      spine and femoral neck before and after bisphosphonate therapy. Data were pooled
      for summary estimates by using weighted mean differences of absolute change in
      BMD. An analysis of covariance was performed, adjusted for individual baseline
      values, treatment arm and individual trial. RESULTS: Five studies involving 180
      participants were included in our meta-analysis. Treatment with bisphosphonates
      showed a substantial effect in preventing post-transplant osteodystrophy. BMD
      decline at the lumbar spine within 6-12 months after transplantation was
      significantly reduced by 0.06 g/cm(2) in patients treated with bisphosphonates
      (95% CI 0.05-0.08 g/cm(2)). At the femoral neck, the loss of BMD was reduced by
      0.05 g/cm(2) during this period (95% CI 0.0-0.11 g/cm(2)), reaching just non
      statistical significance. This benefit of bone loss prevention could be reached
      without major side effects. CONCLUSION: Bisphosphonates are effective in
      preventing bone loss in the early post-transplant period.

PMID- 16574685
TI  - Ramping up endogenous defences against chronic kidney disease.

PMID- 16574686
TI  - Renal transplant dysfunction--importance quantified in comparison with
      traditional risk factors for cardiovascular disease and mortality.
AB  - BACKGROUND: Renal transplant recipients (RTR) mainly die of premature
      cardiovascular disease. Traditional cardiovascular disease risk factors are
      prevalent in RTR. Additionally, non-traditional risk factors seem to contribute
      to the high risk. The impact of renal dysfunction was compared with traditional
      risk factors for cardiovascular morbidity and mortality in 1052 placebo-treated
      patients of the ALERT trial. METHODS: All patients were on cyclosporine-based
      immunosuppressive therapy, follow-up was 5-6 years and captured endpoints
      included cardiac death, non-cardiovascular death, all-cause mortality, major
      adverse cardiac event (MACE), non-fatal myocardial infarction (MI) and stroke.
      RESULTS: A calculated 84 micromol/l increase in serum creatinine was needed to
      double the risk for cardiac death, an increase of 104 micromol/l to double the
      risk for non-cardiovascular death and an increase of 92 micromol/l to double the
      risk for all-cause mortality. MACE risk was doubled if serum creatinine was
      elevated by 141 micromol/l, age was increased by 23 years, or LDL-cholesterol by
      2 mmol/l. Diabetes increased the incidences of cardiac death, all-cause
      mortality, MACE, stroke and non-fatal MI. A serum creatinine increase of
      approximately 130 micromol/l, or approximately 20 years increase in age was
      calculated as similar in risk for cardiac death, all-cause mortality and MACE,
      and comparable to risk of diabetes in RTR. CONCLUSION: An increase in serum
      creatinine of 80-100 micromol/l doubles the risk for cardiac death, non
      cardiovascular death and all-cause mortality in RTR. An increase of 130
      micromol/l in serum creatinine or approximately 20 years increase in age is
      comparable to risk of diabetes.

PMID- 16574687
TI  - Quantitative analysis of type IV collagen subchains in the glomerular basement
      membrane of patients with Alport syndrome with confocal microscopy.
AB  - BACKGROUND: Alport syndrome (AS) is an inherited nephropathy characterized by
      glomerular basement membrane (GBM) abnormalities due to mutations in the type IV
      collagen genes. Through immunofluorescence analysis, the absence of alpha3(IV),
      alpha4(IV) and alpha5(IV) chains within the GBM has been shown in the majority of
      AS cases. In some atypical AS cases, however, staining of the GBM with antibodies
      against the alpha3(IV), alpha4(IV) and alpha5(IV) chains appeared normal. In this
      study, we studied these atypical AS cases by quantitative analysis of the
      expression of type IV collagen subchains in GBM. METHODS: Twelve patients
      diagnosed with AS, yet having normal staining for alpha3(IV) and alpha5(IV)
      chains in the GBM, were recruited. Quantitative analysis of type IV collagen
      subchains in the GBM was performed using confocal microscopy and
      immunofluorescence double label techniques. RESULTS: The absolute amounts of
      alpha3(IV), alpha4(IV) and alpha5(IV) were significantly lower in AS patients
      than that in normal subjects, associated with up-regulated expression of type IV
      collagen in GBM. It was found that eight cases had decreased ratios of
      alpha3(IV)/IV, alpha4(IV)/IV and alpha5(IV)/IV in the GBM simultaneously; one had
      reduced levels of alpha3(IV)/IV and alpha5(IV)/IV but had a normal level of
      alpha4(IV)/IV, and one had reduced alpha3(IV)/IV with normal alpha4(IV)/IV and
      alpha5(IV)/IV levels. The remaining two patients had normal ratios of
      alpha3(IV)/IV, alpha4(IV)/IV and alpha5(IV)/IV. CONCLUSIONS: Confocal analysis
      demonstrated for the first time that the ratios of alpha3(IV)/IV, alpha4(IV)/IV
      and alpha5(IV)/IV in the GBM decreased in patients with AS, even though routine
      immunofluorescence staining for alpha(IV) chains appeared normal. This result not
      only sheds light on the pathogenesis of AS, but also provides an alternative
      approach to diagnose atypical AS cases.

PMID- 16574688
TI  - Refined characterization of the association between kidney function and mortality
      in patients undergoing cardiac catheterization.
AB  - AIMS: Chronic kidney disease is associated with an increased risk of
      cardiovascular morbidity and mortality. The level of kidney function at which
      this risk increases remains to be determined. We sought to characterize the
      relationship between kidney function and survival among patients with
      cardiovascular disease (CVD) undergoing cardiac catheterization using estimated
      glomerular filtration rate (eGFR) and graded refinements in the classification of
      kidney function. METHODS AND RESULTS: We included 8521 of 11 778 (72.3%)
      consecutive patients undergoing cardiac catheterization between 1 January 1999
      and 31 December 2001 from the Alberta Provincial Project for Outcome Assessment
      in Coronary Heart Disease database. eGFR as a categorical and continuous variable
      was used to define kidney function. The outcome was all-cause mortality. During a
      median (interquartile range) follow-up of 2.2 (1.5-3.1) years, and after
      adjustment for clinical risk factors and severity of coronary disease, there was
      a steady incremental decrease in survival post-catheterization corresponding to a
      decline in eGFR categories of 10 mL/min/1.73 m(2). When eGFR was modelled as a
      continuous variable, there was an increased risk of death noted at an eGFR below
      79 mL/min/1.73 m(2). Below an eGFR of 70 mL/min/1.73 m,(2), there was an
      approximate 17.2% relative increase in risk for every 10 unit decrease in eGFR
      (95% CI 8.4-26.6%). CONCLUSION: The risk of death post-cardiac catheterization is
      elevated when eGFR is < or =79 mL/min/1.73 m(2). These findings provide
      considerable refinement in our understanding of eGFR as a powerful prognostic
      marker in patients with CVD undergoing cardiac catheterization.

PMID- 16574689
TI  - Left intraventricular myocardial deformation dyssynchrony identifies responders
      to cardiac resynchronization therapy in patients with heart failure.
AB  - AIMS: We tested the hypothesis that dyssynchrony of left ventricular (LV)
      myocardial deformation evaluated by ultrasound can predict success of cardiac
      resynchronization therapy (CRT) in patients with heart failure (HF). METHODS AND
      RESULTS: Thirty-seven patients with dilated cardiomyopathy, New York Heart
      Association class III-IV, LV ejection fraction (EF) < or =35%, QRS > 120 ms were
      studied before, at pre-discharge, and after 3 and 6 months of CRT. The M-mode
      peak septal-to-posterior wall motion and thickening delay (SPWMD and SPWTD, ms)
      and the standard deviation of the averaged time-to-peak strain (TPS-SD, ms) of 12
      middle and basal LV segments obtained from the three standard apical views were
      calculated. Responders were defined at month 6 by > or =20% EF increase and/or >
      or =15% end-systolic volume (ESV) decrease with respect to baseline. Baseline
      SPWTD (not SPWMD) and TPS-SD differentiated responders from non-responders with
      good accuracy and reproducibility. A value > or =194 ms for SPWTD and > or =60 ms
      for TPS-SD was significantly associated with responder identification. Baseline
      dyssynchrony parameters correlated significantly with EF (r = 0.53 for SPWTD and
      r = 0.86 for TPS-SD) and ESV variations (r = -0.42 for SPWTD and r = -0.73 for
      TPS-SD). CONCLUSION: Patients with chronic HF should undergo ultrasound
      evaluation to quantify dyssynchrony of LV myocardial deformation, which would
      help identifying CRT responders.

PMID- 16574690
TI  - Adenosine test in the diagnosis of unexplained syncope: marker of conducting
      tissue disease or neurally mediated syncope?
AB  - Adenosine test (supine administration of a 20 mg intravenous bolus with
      electrocardiographic and blood pressure monitoring) has been endorsed by the
      European Society of Cardiology guidelines on syncope management as an
      'experimental' test in the diagnosis of unexplained syncope. The test is quick
      and cheap, but there is no consensus as to what condition, if any, the adenosine
      test is exposing, with conducting tissue disease and neurally mediated syncope
      proposed by various authors. In this article, we review the possible mechanisms
      underlying a positive adenosine test, its safety, and a comprehensive examination
      of the literature supporting each of the putative causal diagnoses.

PMID- 16574691
TI  - Neither host-specific nor random: vascular epiphytes on three tree species in a
      Panamanian lowland forest.
AB  - BACKGROUND AND AIMS: A possible role of host tree identity in the structuring of
      vascular epiphyte communities has attracted scientific attention for decades.
      Specifically, it has been suggested that each host tree species has a specific
      subset of the local species pool according to its own set of properties, e.g.
      physicochemical characteristics of the bark, tree architecture, or leaf phenology
      patterns. METHODS: A novel, quantitative approach to this question is presented,
      taking advantage of a complete census of the vascular epiphyte community in 0.4
      ha of undisturbed lowland forest in Panama. For three locally common host-tree
      species (Socratea exorrhiza, Marila laxiflora, Perebea xanthochyma) null models
      were created of the expected epiphyte assemblages assuming that epiphyte
      colonization reflected random distribution of epiphytes in the forest. KEY
      RESULTS: In all three tree species, abundances of the majority of epiphyte
      species (69-81 %) were indistinguishable from random, while the remaining species
      were about equally over- or under-represented compared with their occurrence in
      the entire forest plot. Permutations based on the number of colonized trees
      (reflecting observed spatial patchiness) yielded similar results. Finally, a
      third analysis (canonical correspondence analysis) also confirmed host-specific
      differences in epiphyte assemblages. In spite of pronounced preferences of some
      epiphytes for particular host trees, no epiphyte species was restricted to a
      single host. CONCLUSIONS: The epiphytes on a given tree species are not simply a
      random sample of the local species pool, but there are no indications of host
      specificity either.

PMID- 16574692
TI  - A Rudimentary labellar speculum in Cymbidium lowianum (Rchb.f.) Rchb.f. and
      Cymbidium devonianum Paxton (Orchidaceae).
AB  - BACKGROUND AND AIMS: The labellar 'hairs' of some Cymbidium spp. are said to be
      thin-walled and to contain 'plasma', oil and sugars and it has long been
      speculated that they may function as food-hairs. However, the present authors'
      preliminary studies showed that certain atypical papillae may have a different
      role and, by reflecting light, function as a speculum. The purpose of the paper
      is to test this hypothesis. METHODS: Light microscopy, scanning electron
      microscopy, transmission electron microscopy, histochemistry and ultraviolet
      photography were used to investigate the structure, food content and light
      reflecting properties of these papillae. KEY RESULTS AND CONCLUSIONS: The
      labellum of Cymbidium lowianum (Rchb.f.) Rchb.f. is densely clothed with
      obconical to conical papillae with wide bases and pointed tips. However, on
      either side of the median axis of the lip occur silvery patches comprising
      papillae with truncated tips and it is thought that these reflect light and
      thereby attract insect pollinators. Similar patches are also found in Cymbidium
      devonianum Paxton, and in both species, they are set against a reddish
      background, which, since bees cannot perceive this colour, probably appears dark
      to the insect thus enhancing the visual impact of the light-reflecting patches.
      In Cymbidium tigrinum Parish ex Hook. and Cymbidium mastersii Griff. ex Lindl.,
      however, the labellum is mainly white and no light-reflecting patches were
      observed. Instead, unlike C. lowianum and C. devonianum, these species are highly
      fragrant and the attraction of insects probably depends to a greater extent on
      olfactory cues. In C. lowianum both types of papillae contain protein, starch and
      lipid bodies but only protein is seemingly present at elevated concentrations.
      However, lipoidal material also occurs upon the surface of the labellum and it is
      possible that this may be gathered by insects as reported for C. iridifolium A.
      Cunn (syn. C. madidum Lindl.). The labellar papillae of C. lowianum, thus, have
      the potential to function as food-hairs, although direct evidence for this is
      lacking.

PMID- 16574693
TI  - Strigolactones: chemical signals for fungal symbionts and parasitic weeds in
      plant roots.
AB  - AIMS: Arbuscular mycorrhizae are formed between >80 % of land plants and
      arbuscular mycorrhizal (AM) fungi. This Botanical Briefing highlights the
      chemical identification of strigolactones as a host-recognition signal for AM
      fungi, and their role in the establishment of arbuscular mycorrhizae as well as
      in the seed germination of parasitic weeds. SCOPE: Hyphal branching has long been
      described as the first morphological event in host recognition by AM fungi during
      the pre-infection stages. Host roots release signalling molecules called
      'branching factors' that induce extensive hyphal branching in AM fungi.
      Strigolactones exuded from host roots have recently been identified as an inducer
      of hyphal branching in AM fungi. Strigolactones are a group of sesquiterpenes,
      previously isolated as seed germination stimulants for the parasitic weeds Striga
      and Orobanche. Parasitic weeds might find their potential hosts by detecting
      strigolactones, which are released from plant roots upon phosphate deficiency in
      communication with AM fungi. In addition to acting as a signalling molecule,
      strigolactones might stimulate the production of fungal symbiotic signals called
      'Myc factors' in AM fungi. CONCLUSIONS: Isolation and identification of plant
      symbiotic signals open up new ways for studying the molecular basis of plant-AM
      fungus interactions. This discovery provides a clear answer to a long-standing
      question in parasitic plant biology: what is the natural role for germination
      stimulants? It could also provide a new strategy for the management and control
      of beneficial fungal symbionts and of devastating parasitic weeds in agriculture
      and natural ecosystems.

PMID- 16574694
TI  - PseudoPipe: an automated pseudogene identification pipeline.
AB  - MOTIVATION: Mammalian genomes contain many 'genomic fossils' i.e. pseudogenes.
      These are disabled copies of functional genes that have been retained in the
      genome by gene duplication or retrotransposition events. Pseudogenes are
      important resources in understanding the evolutionary history of genes and
      genomes. RESULTS: We have developed a homology-based computational pipeline
      ('PseudoPipe') that can search a mammalian genome and identify pseudogene
      sequences in a comprehensive and consistent manner. The key steps in the pipeline
      involve using BLAST to rapidly cross-reference potential "parent" proteins
      against the intergenic regions of the genome and then processing the resulting
      "raw hits" -- i.e. eliminating redundant ones, clustering together neighbors, and
      associating and aligning clusters with a unique parent. Finally, pseudogenes are
      classified based on a combination of criteria including homology, intron-exon
      structure, and existence of stop codons and frameshifts.

PMID- 16574695
TI  - GenRGenS: software for generating random genomic sequences and structures.
AB  - SUMMARY: GenRGenS is a software tool dedicated to randomly generating genomic
      sequences and structures. It handles several classes of models useful for
      sequence analysis, such as Markov chains, hidden Markov models, weighted context
      free grammars, regular expressions and PROSITE expressions. GenRGenS is the only
      program that can handle weighted context-free grammars, thus allowing the user to
      model and to generate structured objects (such as RNA secondary structures) of
      any given desired size. GenRGenS also allows the user to combine several of these
      different models at the same time.

PMID- 16574696
TI  - SBMLToolbox: an SBML toolbox for MATLAB users.
AB  - SUMMARY: We present SBMLToolbox, a toolbox that facilitates importing and
      exporting models represented in the Systems Biology Markup Language (SBML) in and
      out of the MATLAB environment and provides functionality that enables an
      experienced user of either SBML or MATLAB to combine the computing power of
      MATLAB with the portability and exchangeability of an SBML model. SBMLToolbox
      supports all levels and versions of SBML. AVAILABILITY: SBMLToolbox is freely
      available from http://sbml.org/software/sbmltoolbox

PMID- 16574697
TI  - Construction of null statistics in permutation-based multiple testing for multi
      factorial microarray experiments.
AB  - MOTIVATION: The parametric F-test has been widely used in the analysis of
      factorial microarray experiments to assess treatment effects. However, the
      normality assumption is often untenable for microarray experiments with small
      replications. Therefore, permutation-based methods are called for help to assess
      the statistical significance. The distribution of the F-statistics across all the
      genes on the array can be regarded as a mixture distribution with a proportion of
      statistics generated from the null distribution of no differential gene
      expression whereas the other proportion of statistics generated from the
      alternative distribution of genes differentially expressed. This results in the
      fact that the permutation distribution of the F-statistics may not approximate
      well to the true null distribution of the F-statistics. Therefore, the
      construction of a proper null statistic to better approximate the null
      distribution of F-statistic is of great importance to the permutation-based
      multiple testing in microarray data analysis. RESULTS: In this paper, we extend
      the ideas of constructing null statistics based on pairwise differences to
      neglect the treatment effects from the two-sample comparison problem to the
      multifactorial balanced or unbalanced microarray experiments. A null statistic
      based on a subpartition method is proposed and its distribution is employed to
      approximate the null distribution of the F-statistic. The proposed null statistic
      is able to accommodate unbalance in the design and is also corrected for the
      undue correlation between its numerator and denominator. In the simulation
      studies and real biological data analysis, the number of true positives and the
      false discovery rate (FDR) of the proposed null statistic are compared with those
      of the permutated version of the F-statistic. It has been shown that our proposed
      method has a better control of the FDRs and a higher power than the standard
      permutation method to detect differentially expressed genes because of the better
      approximated tail probabilities.

PMID- 16574698
TI  - SScore: an R package for detecting differential gene expression without gene
      expression summaries.
AB  - SUMMARY: SScore is an R package that facilitates the comparison of gene
      expression between Affymetrix GeneChips using the S-score algorithm. The S-score
      algorithm uses probe level data directly to assess differences in gene
      expression, without requiring a preliminary separate step of probe set expression
      summary estimation. Therefore, the algorithm avoids introduction of error
      associated with the expression summary estimation process and has been
      demonstrated to improve the accuracy of identifying differentially expressed
      genes. The S-score produces accurate results even when few or no replicates are
      available. AVAILABILITY: The R package SScore is available from Bioconductor at
      http://www.bioconductor.org

PMID- 16574699
TI  - Primary unexplained infertility is associated with reduced expression of the T
      regulatory cell transcription factor Foxp3 in endometrial tissue.
AB  - A receptive endometrial environment requires adequate immunological tolerance to
      protect the implanting embryo from maternal immune rejection. Studies in mice
      implicate CD4+CD25+ T-regulatory (Treg) cells as essential mediators of immune
      tolerance in pregnancy. The aim of this study was to evaluate the link between
      Treg cells and fertility in women. Expression of Foxp3, a master regulator of
      Treg cell differentiation, was quantified in endometrial tissue from women
      experiencing primary unexplained infertility and normal fertile women.
      Endometrial biopsies were collected during the mid-secretory phase of the
      menstrual cycle from women meeting rigorously defined criteria for unexplained
      infertility after experiencing repeated failed cycles of IVF treatment
      (infertile, n = 10), or women classified as proven fertile (control, n = 12).
      Expression of Foxp3 mRNA was reduced approximately two-fold in the tissue of
      infertile women. In contrast, mRNAs encoding T cell transcription factors T-bet
      and GATA3, associated with differentiation of Th1 and Th2 CD4+ T cells
      respectively, were unchanged. Treg cell differentiation is controlled by TGFbeta,
      but the relative abundance in endometrial tissue of TGFbeta1, TGFbeta2, TGFbeta3
      mRNAs was not changed in infertile women. Cytokines influencing Th1 and Th2 cell
      differentiation, including IFNgamma, IL-2, IL-4, IL-5, IL-10 and IL-12p40, as
      well as dendritic cell-regulating cytokines IL-1alpha, IL-1beta, IL-6, LIF, GM
      CSF and TNFalpha were also expressed similarly regardless of fertility status.
      The finding of reduced endometrial Foxp3 implicates impaired differentiation of
      uterine T cells into the Treg phenotype as a key determinant of fertility in
      women. The factors underpinning this aberration in the immune response remain to
      be identified.

PMID- 16574700
TI  - Effects of SAPK/JNK inhibitors on preimplantation mouse embryo development are
      influenced greatly by the amount of stress induced by the media.
AB  - Stress-activated protein kinase/c-Jun kinase (SAPK/JNK) is thought to be
      necessary for preimplantation embryonic development (Maekawa et al., 2005).
      However, media increases SAPK/JNK phosphorylation and these levels negatively
      correlate with embryonic development (Wang et al., 2005). Culture-induced stress
      could confuse analysis of the role of SAPK in development. In this study, we
      tested how SAPK/JNK inhibitors influence embryonic development in optimal and non
      optimal media and define the contribution of cell survival and proliferation to
      the embryonic response to these media. SAPK/JNK inhibitors retard embryonic
      development in suboptimal Ham's F10, but improve development in optimal potassium
      (K+) simplex optimized media (KSOM) +AA. In KSOM + amino acids (KSOM+AA), two
      SAPK/JNK inhibitors increase the rate of cavitation and hatching. These data
      suggest that (i) SAPK/JNK mediates the response to culture stress, not normal
      preimplantation embryonic development and (ii) SAPK/JNK inhibitors may be useful
      in ameliorating embryo stress caused by culture. To define the effects of media,
      we assayed the contribution of cell survival and proliferation and the
      differences in total cell number of cultured embryos. Embryos cultured from
      E3.5+24 h in the suboptimal medium (Ham's F10) induced significant but small
      increases in TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end
      labelling (TUNEL) positive cells. Bromodeoxyuridine (BrdU) incorporation in
      suboptimal Ham's F10 was significantly lower than in optimal KSOM+AA, suggesting
      that cell cycle arrest also contributes to slower increase in cell number in
      stressful media. This is the first report where TUNEL and BrdU were both assayed
      to define the relative contribution of cell cycle/S phase commitment and
      apoptosis to lessened cell number increase during embryo culture.

PMID- 16574701
TI  - Tumour necrosis factor-related apoptosis-inducing ligand and osteoprotegerin
      serum levels in psoriatic arthritis.
AB  - OBJECTIVES: The degree of bone loss in patients with psoriatic arthritis (PsA)
      has not been well-defined. We tested the hypothesis, whether serum levels of
      tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), a pro-apoptotic
      cytokine and osteoprotegerin (OPG), an anti-osteoclastic cytokine, are associated
      with changes in biochemical markers of bone turnover or bone mineral density
      (BMD) in patients with PsA. METHODS: In a cross-sectional study, we evaluated
      biochemical markers of bone turnover, BMD and serum levels of TRAIL and OPG in
      116 patients with PsA (mean age: 52+/-13 yrs). RESULTS: In patients with PsA,
      osteopenia was present in one-third of women and men, while osteoporosis was more
      frequent in men (10.2%) than in women (1.75%). Serum levels of TRAIL were
      significantly higher in patients with PsA (66.1+/-45.3 pmol/l) compared with
      controls (50.0+/-20.1 pmol/l, P<0.01), whereas OPG serum levels were not
      different. There were no associations between TRAIL or OPG serum levels with BMD
      and biochemical markers of bone turnover. However, TRAIL serum levels were
      associated with C-reactive protein (CRP) levels (R = 0.201, P<0.05), whereas OPG
      serum levels were associated with the erythrocyte sedimentation rate (R=0.215,
      P<0.05). CONCLUSION: In summary, BMD is decreased in one-third of patients with
      PsA, and predominantly men with PsA suffer from osteoporosis. While TRAIL serum
      levels are increased in PsA and correlated with CRP levels, neither TRAIL nor OPG
      serum levels are correlated with BMD or markers of bone metabolism.

PMID- 16574702
TI  - A tale of two Es.

PMID- 16574703
TI  - Alcohol alternatives--a goal for psychopharmacology?

PMID- 16574704
TI  - The regulatory challenges in engineering a safer tipple.

PMID- 16574705
TI  - For alcohol alternatives, the science is not the hardest part.

PMID- 16574706
TI  - Alcohol alternatives--a goal for psychopharmacology?

PMID- 16574707
TI  - "Alcohol alternatives: a goal for psychopharmacology?" by David J. Nutt.

PMID- 16574708
TI  - Harm reduction: lessons learned from tobacco control.

PMID- 16574710
TI  - Selecting antipsychotics in schizophrenia: lessons from CATIE.

PMID- 16574711
TI  - Memory deficits in abstinent MDMA (ecstasy) users: neuropsychological evidence of
      frontal dysfunction.
AB  - Chronic administration of the common club drug 3,4-methylenedioxymethamphetamine
      (MDMA, ecstasy) is associated with long-term depletion of serotonin (5-HT) and
      loss of 5-HT axons in the brains of rodents and non-human primates, and evidence
      suggests that recreational MDMA consumption may also affect the human
      serotonergic system. Moreover, it was consistently shown that abstinent MDMA
      users have memory deficits. Recently, it was supposed that these deficits are an
      expression of a temporal or rather hippocampal dysfunction caused by the
      serotonergic neurotoxicity of MDMA. The aim of this study is to examine the
      memory deficits of MDMA users neuropsychologically in order to evaluate the role
      of different brain regions. Nineteen male abstinent MDMA users, 19 male abstinent
      cannabis users and 19 male drug-naive control subjects were examined with a
      German version of the Rey Auditory Verbal Learning Test (RAVLT). MDMA users
      showed widespread and marked verbal memory deficits, compared to drug-naive
      controls as well as compared to cannabis users, whereas cannabis users did not
      differ from control subjects in their memory performance. MDMA users revealed
      impairments in learning, consolidation, recall and recognition. In addition, they
      also showed a worse recall consistency and strong retroactive interference
      whereby both measures were previously associated with frontal lobe function.
      There was a significant correlation between memory performance and the amount of
      MDMA taken. These results suggest that the memory deficits of MDMA users are not
      only the result of a temporal or hippocampal dysfunction, but also of a
      dysfunction of regions within the frontal cortex.

PMID- 16574712
TI  - MDMA polydrug users show process-specific central executive impairments coupled
      with impaired social and emotional judgement processes.
AB  - In recent years working memory deficits have been reported in users of MDMA (3,4
      methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the
      impact of MDMA use on three separate central executive processes (set shifting,
      inhibition and memory updating) and also on "prefrontal" mediated social and
      emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non
      ecstasy user controls completed a general drug use questionnaire, the Brixton
      Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory
      updating), Inhibition of Return (inhibition), an emotional intelligence scale,
      the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX).
      Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments
      in set shifting and memory updating, and also in social and emotional judgement
      processes. The latter two deficits remained significant after controlling for
      other drug use. These data lend further support to the proposal that cognitive
      processes mediated by the prefrontal cortex may be impaired by recreational
      ecstasy use.

PMID- 16574713
TI  - Memory function and serotonin transporter promoter gene polymorphism in ecstasy
      (MDMA) users.
AB  - Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to
      damage brain serotonin (5-HT) neurons in animals and possibly humans, little is
      known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on
      functions in which 5-HT is involved, such as cognitive function. Because 5-HT
      transporters play a key element in the regulation of synaptic 5-HT transmission
      it may be important to control for the potential covariance effect of a
      polymorphism in the 5-HT transporter promoter gene region (5-HTTLPR) when
      studying the effects of MDMA as well as cognitive functioning. The aim of the
      study was to investigate the effects of moderate and heavy MDMA use on cognitive
      function, as well as the effects of long-term abstention from MDMA, in subjects
      genotyped for 5-HTTLPR. A second aim of the study was to determine whether these
      effects differ for females and males. Fifteen moderate MDMA users (<55 lifetime
      tablets), 22 heavy MDMA+ users (>55 lifetime tablets), 16 ex-MDMA+ users (last
      tablet > 1 year ago) and 13 controls were compared on a battery of
      neuropsychological tests. DNA from peripheral nuclear blood cells was genotyped
      for 5-HTTLPR using standard polymerase chain reaction methods.A significant group
      effect was observed only on memory function tasks (p = 0.04) but not on reaction
      times (p = 0.61) or attention/executive functioning (p = 0.59). Heavy and ex
      MDMA+ users performed significantly poorer on memory tasks than controls. In
      contrast, no evidence of memory impairment was observed in moderate MDMA users.
      No significant effect of 5-HTTLPR or gender was observed. While the use of MDMA
      in quantities that may be considered "moderate" is not associated with impaired
      memory functioning, heavy use of MDMA use may lead to long lasting memory
      impairments. No effect of 5-HTTLPR or gender on memory function or MDMA use was
      observed.

PMID- 16574714
TI  - Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a
      clubbing population.
AB  - Despite the common use of MDMA (ecstasy) in the UK, the mechanism underlying
      associated potentially fatal cerebral oedema is unclear. We used a new
      experimental approach working directly with clubbers to perform a study on 30 (17
      male) experienced clubbers (mean 6.6 years of clubbing). Pre- and post-clubbing
      measurements were performed to compare plasma levels of pituitary hormones
      (vasopressin, oxytocin), plasma and urine osmolality, urinary pH, and plasma
      sodium and urea. Ecstasy consumption was confirmed by using urinary drug
      screening pre- and post-clubbing. MDMA was detected in the urine samples of 17
      subjects, three of which tested positive during pre-clubbing tests. Mean plasma
      vasopressin concentration increased in the MDMA group (1.28 +/- 0.29 to 1.43 +/-
      0.41 pmol/l), but fell in other participants (1.23 +/- 0.42 to 1.16 +/- 0.0.34
      pmol/l). Similarly, mean plasma oxytocin concentrations increased after ingestion
      of MDMA (2.02 +/- 0.29 to 2.43 +/- 0.24 pmol/l), but fell in the group that did
      not use MDMA (2.17 +/- 0.36 pmol/l to 1.89 +/- 0.37 pmol/l). There was a
      significant group by time interaction for plasma osmolality and plasma sodium (p
      = 0.001 and p = 0.003, respectively) and between change in urinary osmolality (p
      < 0.001) and MDMA use, with the pattern of change being consistent with the
      induction of inappropriate vasopressin secretion (also known as SIADH) by MDMA.
      This report demonstrates SIADH in ecstasy-using "clubbers", which has important
      clinical implications.

PMID- 16574715
TI  - Recreational ecstasy use and depression.
AB  - Research in laboratory animals has shown that 3,4-methylenedioxymethamphetamine
      (MDMA or ecstasy) destroys serotonergic axons in the brain at certain doses.
      Serotonin is known to take part in the regulation of mood in humans. Many
      researchers have hypothesized that if recreational ecstasy use destroys
      serotonergic axons, then a corresponding decline in the mood of ecstasy users
      should be seen. The purpose of the present study was to look at the relationship
      between recreational ecstasy use and depression as measured by the Beck
      Depression Inventory-II. No significant differences were found between Beck
      Depression Inventory-II scores of heavy ecstasy users and ecstasy-naive college
      students. No significant relationships were found between Beck Depression
      Inventory-II scores and any of the measures of ecstasy use. Most ecstasy users
      who had been diagnosed with a psychiatric disorder reported that being diagnosed
      preceded their use of ecstasy.

PMID- 16574716
TI  - Problematic versus non-problematic ecstasy/MDMA use: the influence of drug usage
      patterns and pre-existing psychiatric factors.
AB  - Recreational ecstasy (3,4-methylenedioxymethamphetamine; MDMA) use has been
      increasingly associated with a number of psychiatric symptoms and psychological
      problems. However, previous studies assessing possible psychopathological effects
      have not identified whether users consider their ecstasy use "problematic" or
      not. In addition, research has generally failed to address the potential role of
      premorbid psychiatric status. This study aimed to assess whether premorbid
      psychiatric history and/or patterns of ecstasy use would be associated with the
      degree of self-reported problems attributable to ecstasy. Problematic ecstasy
      users (n = 53) who had reported problems attributable to their ecstasy use were
      compared with non-problematic ecstasy users (n = 62), polydrug controls (n = 62)
      and illegal drug-naive controls (n = 111) on a recreational drug use
      questionnaire; a questionnaire, which ascertained personal and family psychiatric
      histories, and the Brief Symptom Inventory (BSI). Problematic ecstasy users
      exhibited significantly higher scores on a number of dimensions of the BSI
      compared to illegal drug-naive and/or polydrug controls. Problematic ecstasy
      users also exhibited significantly elevated scores on somatization, depression,
      anxiety and negative psychobiology compared to non-problematic ecstasy users. BSI
      scores for the non-problematic ecstasy users did not differ from polydrug or
      illegal drug-naive controls. Problematic ecstasy users reported significantly
      higher levels of ecstasy use, including lifetime consumption, average dosage and
      binge consumption compared to non-problematic ecstasy users. Additionally, a
      greater number of problematic ecstasy users reported personal and family
      psychiatric histories compared to controls and non-problematic ecstasy users.
      This study demonstrates two distinct ecstasy using groups: non-problematic
      ecstasy users who are not showing signs of psychopathology and problematic
      ecstasy users who are showing evidence of a range of symptoms. This data
      therefore partially supports the link between ecstasy dosage and negative
      psychological sequelae, but highlights the importance of the need to consider
      ecstasy-related attributions, pre-existing mental health status and
      vulnerability.

PMID- 16574717
TI  - Eating attitudes, weight concerns and beliefs about drug effects in women who use
      ecstasy.
AB  - The drug ecstasy has appetite suppressant and exercise promoting effects that may
      appeal to young women who are concerned about weight and body image. This study
      therefore aimed to determine whether young women who use ecstasy differ from
      those who do not use this drug in concerns about eating and weight, and in
      beliefs about how these are affected by recreational drugs. One hundred and
      thirty young women, all cigarette smokers, were recruited; 73 who used ecstasy
      were compared with 57 who did not. All were assessed on Garner's (1991) Eating
      Disorder Inventory (EDI-2), body mass index (BMI), depression and beliefs about
      the effects of different drugs on appetite, exercise and weight. The two groups
      did not differ on number of cigarettes smoked per day, depression scores, current
      BMI, lowest achieved BMI or ideal BMI. Ecstasy users had significantly higher
      scores than controls on four of the 11 sub-scales of the EDI: bulimia, impulse
      dysregulation, social insecurity and interpersonal distrust. For ecstasy users,
      scores on all four scales correlated positively with frequency of ecstasy use.
      However there were no group differences in "drive for thinness" or "body
      dissatisfaction" which may suggest that differences on other factors are related
      more to use of club drugs than to any specific eating pathology. Ecstasy users
      were more likely than controls to agree that ecstasy aids weight loss and that
      they exercise more when they use drugs. However, our findings indicated that
      women are not using ecstasy as a deliberate means of weight control.

PMID- 16574718
TI  - Self-reported ecstasy use: the impact of assessment method on dosage estimates in
      recreational users.
AB  - While research has associated recreational ecstasy use with negative outcomes,
      there remain a number of methodological limitations of human studies. The present
      study examined the impact of self-report methodology on lifetime ecstasy dosage
      figures using three estimation methods: a single question estimation, a context
      based timeline method and a quantity-frequency method. We used a repeated
      measures design, testing 38 participants aged over 18 years who reported using
      ecstasy on ten or more occasions. Methodology was found to impact on estimations
      made, with the timeline method producing higher figures than the single question.
      While single question and timeline estimations were positively correlated, there
      was no relationship between either of these methods and the quantity-frequency
      method. The present findings are in keeping with indications in the alcohol and
      other drug literature that the use of contextual memory cues increases accuracy
      of recall as indicated by higher estimations, and that quantity-frequency methods
      may not adequately assess variability in lifetime drug-use patterns.

PMID- 16574719
TI  - Users' perceptions of the risks and effects of taking ecstasy (MDMA): a
      questionnaire study.
AB  - This self-report questionnaire study examined ecstasy users' perceptions of the
      risks associated with their use of ecstasy, their precautions against such risks,
      and its perceived effects on their lives. Gender differences in these areas were
      also explored. The sample comprised 328 ecstasy users (139 female, 187 male, one
      transsexual) with a mean age of 22.5 years (SD = 4.9 years). Questionnaires were
      completed either in hard copy or through a website concerned with ecstasy use.
      The results showed that friends were the most common source of information about
      ecstasy for the sample overall, although females were more likely to utilize this
      source than males. None of the five categories of perceived risk (e.g.
      psychiatric, physical) showed a significant gender difference. Males were more
      likely to take rest breaks whilst females were more likely to limit consumption
      as a precaution against harm. Three factors emerged from a principal components
      analysis concerning perceived personal change since initiation of ecstasy use.
      Factor 1 (23.8% of the variance) concerned negative experiences (e.g.
      depression). Factor 2 (22.0% of the variance) concerned positive personal
      qualities (e.g. caring). Factor 3 (10.5% of the variance) concerned selective
      aspects of functioning (e.g. alertness). The pattern of Factor 1 and Factor 2
      scores over time suggested that 6 years since initiation of ecstasy use might be
      a time when some long-term users may be open to reassess their use of the drug.
      Broader implications of the findings for health education initiatives aimed at
      ecstasy users are discussed.

PMID- 16574720
TI  - Ecstasy (MDMA, MDA, MDEA, MBDB) consumption, seizures, related offences, prices,
      dosage levels and deaths in the UK (1994-2003).
AB  - In the last decade, a global trend of escalating ecstasy (MDMA, MDA, MDEA, MBDB)
      use was observed. Mentions on medical death certificates, last year's ecstasy
      use, number of drug offenders, seizures, prices and dosage levels figures were
      used for this descriptive and correlational study. Figures (1994-2003) were taken
      from the UK General Mortality Registers, from the Home Office Statistical
      Bulletins, from the British Crime Survey and from those reported to both the
      National Crime Intelligence and Forensic Science Services. A total of 394 ecstasy
      deaths mentions were here identified from the UK; in 42% of cases ecstasy was the
      sole drug mentioned. Overall, number of fatalities showed a year-per-year
      increase and positively correlated with: prevalence of last year's use (p <
      0.01); number of offenders (p < 0.01) and number of seizures (p < 0.01) but
      negatively correlated with ecstasy price (p < 0.05). Price negatively correlated
      with: prevalence of last year's use (p < 0.001) and number of seizures (p <
      0.01); but positively correlated with average MDMA dosage per tablet (p < 0.01).
      MDA, MDEA and MBDB accounted for a significant proportion of tablets only up to
      1997, but not afterwards. Increasing production with a concomitant decrease in
      ecstasy price may have facilitated an increase in consumption levels and this, in
      turn, may have determined an increase in number of ecstasy deaths mentions. Only
      medical death certificates and not coroners' reports at the end of their inquests
      were here analysed; no data were available in respect of other drugs use and
      toxicology results.

PMID- 16574721
TI  - Metallothionein isoform II expression in hyperplastic, dysplastic and neoplastic
      prostatic lesions.
AB  - BACKGROUND: Metallothionein is a low-molecular-weight cysteine-rich protein that
      has the ability to bind and sequestrate heavy metal ions. It is associated with
      metalloregulatory functions such as cell proliferation, growth and
      differentiation. AIMS: To investigate the expression of metallothionein in
      hyperplastic, dysplastic and neoplastic prostatic lesions and to correlate its
      expression with histological grade of prostatic carcinoma. METHOD: The study was
      carried out on formalin-fixed and paraffin-wax-embedded tissue blocks from 8
      patients with benign prostatic hyperplasia, 6 patients with prostatic
      intraepithelial neoplasia (PIN) and 30 patients with prostatic carcinoma, using
      the streptavidin-biotin technique. The histological grade was defined and the
      carcinomas were divided into low-grade (Gleason Score 2-4), 12 moderate grade
      (Gleason Score 5-6) and 10 high-grade (Gleason Score 7-10) carcinomas. RESULTS:
      Patchy metallothionein staining of epithelial cells was observed in normal and
      benign prostatic tissues. All cases of PIN and 20 of 30 patients with prostatic
      carcinoma showed positive staining for metallothionein. Metallothionein
      expression considerably increased from low-grade to high-grade tumours. The
      proportion of cells staining positively for metallothionein was directly
      correlated with histological grade of prostatic carcinoma. The epithelial cells
      lack uniformity in staining intensity, but the percentage of strongly positive
      cells increased with the histological grade of prostatic carcinoma. CONCLUSIONS:
      The high incidence of metallothionein expression in PIN in our study suggests
      that it is associated with early prostate tumorigenesis. Also, metallothionein
      expression was directly correlated with the histological grade of prostatic
      carcinoma, suggesting that metallothionein may be a useful marker for predicting
      the prognosis of prostate cancer.

PMID- 16574723
TI  - Superimposed high-frequency jet ventilation (SHFJV) for endoscopic
      laryngotracheal surgery in more than 1500 patients.
AB  - BACKGROUND: Superimposed high-frequency jet ventilation (SHFJV), which does not
      require any tracheal tubes or catheters, was developed specifically for use in
      laryngotracheal surgery. SHFJV uses two jet streams with different frequencies
      simultaneously and is applied in the supraglottic space using a jet laryngoscope
      and jet ventilator. METHODS: Between 1990 and 2004, SHFJV was studied in 1515
      consecutive patients (including 158 children requiring laryngotracheal surgery)
      prospectively. Ventilation was performed with an air/oxygen mixture and
      anaesthesia was administered i.v. RESULTS: Adequate oxygenation and ventilation
      was achieved in 1512 patients. Arterial blood gas analyses (BGA) were performed
      between 1990 and 1994; thereafter BGA was only performed in patients with high
      grade stenosis of the larynx/trachea or high-risk patients [n=623, mean Pa(O(2))
      133.8 (39.4) mm Hg and mean Pa(CO(2)) 42.3 (10.1) mm Hg]. There were no
      significant changes in Pa(O(2)) or Pa(CO(2)) during the entire period of SHFJV.
      No complications secondary to the ventilation technique were observed; in
      particular, no barotrauma occurred. Three patients required tracheal intubation.
      SHFJV was also successfully used for laser surgery (n=312). It proved to be a
      safe mode of ventilation without any complications such as airway fire, major
      haemorrhage, or aspiration of debris. CONCLUSION: SHFJV is an advanced
      ventilation mode playing a pivotal role in the (open) ventilatory
      support/ventilation of patients with laryngotracheal stenosis. It is particularly
      indicated in cases of severe stenosis and offers optimal conditions for
      laryngotracheal surgery, including laser surgery and stent implantation
      techniques.

PMID- 16574722
TI  - Alternative splicing factor ASF/SF2 is down regulated in inflamed muscle.
AB  - BACKGROUND: In our recent studies, alternative splicing has been shown to have a
      major role in inflammation and autoimmune muscle diseases. AIM: To examine the
      novel hypothesis that the expression of an essential alternative splicing factor,
      alternative splicing factor 2 (ASF/SF2), is modulated in muscle inflammation.
      METHODS: ASF/SF2 expression in muscle biopsy samples from eight patients with
      inflammatory myopathy and six non-myositic controls was determined by using
      western blot with anti-ASF/SF2 antibodies. To further elucidate the mechanism of
      reduced ASF/SF2 expression in inflamed muscle, differentiated C2C12 myotubes were
      stimulated with proinflammatory cytokine tumour necrosis factor alpha (TNFalpha),
      followed by western blot analysis of ASF/SF2 expression. RESULTS: ASF/SF2
      expression in the muscle biopsy samples from patients with inflammatory myopathy
      was found to be lower (mean of relative densitometric units 41.1 (2SD 20.7)) than
      that of the non-myositic controls (mean of relative densitometric units 76.7
      (39.6); p<0.05). In addition to this, ASF/SF2 expression was seen to be
      significantly down regulated (sevenfold) in C2C12 myotubes compared with
      expression variations in the beta-actin control (0.62-fold; mean 1.22 (0.40);
      p<0.05). CONCLUSION: Collectively, it is shown, for the first time, that
      alternative splicing factor ASF/SF2 is down regulated in autoimmune inflammatory
      myositis-potentially via a TNFalpha-mediated pathway. The development of (1)
      novel autoantigen isoform microarrays for disease diagnosis and prognosis; (2)
      novel autoantigen-tolerising treatments for autoimmune diseases; and (3) novel
      splicing-redirection treatments can be facilitated by the ongoing study of
      alternative splicing of autoantigen transcripts.

PMID- 16574724
TI  - Too old to thrombolyse?

PMID- 16574725
TI  - Traumatic homonymous hemianopia.
AB  - OBJECTIVE: To describe the characteristics of patients with homonymous hemianopia
      from traumatic brain injury (TBI) seen in our unit between 1989 and 2004.
      METHODS: Only patients with a history of TBI, who had detailed clinical
      information and results of neuroimaging, were included in our study. Demographic
      characteristics, clinical features, types of visual field defects, location of
      lesion and evolution of visual field defects were recorded. RESULTS: Of the 880
      patients with homonymous hemianopia seen in our unit, 103 patients (112 with
      homonymous hemianopia) had TBI (74 men and 29 women, mean age 30.7 (SD 15.3)
      years). Median time from injury to initial visual field testing was 5 (range 0.5
      360) months. In all, 64 (57.1%) patients sustained injuries that were motor
      vehicle-related; 19 (17%) violence-related; 17 (15.2%) due to falls; and 12
      (10.7%) because of other blunt head trauma. Visual field defects included
      complete homonymous hemianopia in 44 (39.3%) patients and incomplete homonymous
      hemianopia in 68 (60.7%) patients. The lesion was occipital in 14 (12.5%)
      patients, associated with optic radiation in 26 (23.2%) and the optic tract in 12
      (10.7%), and multiple in 60 (53.6%). CONCLUSION: Most cases of homonymous
      hemianopia from TBI were motor vehicle-related. Patients were younger, more often
      male, and had multiple brain lesions more often than patients with homonymous
      hemianopia from causes other than TBI. A median delay of 5 months was observed
      before the documentation of the homonymous hemianopia, which may have a major
      effect on the success of rehabilitation and driving training in these young
      patients.

PMID- 16574726
TI  - Idiopathic generalised epilepsy: a pilot study of memory and neuronal dysfunction
      in the temporal lobes, assessed by magnetic resonance spectroscopy.
AB  - BACKGROUND: The memory deficits in patients with temporal lobe epilepsy (TLE) are
      associated with epileptogenic lesions of the temporal lobes, especially
      hippocampal sclerosis. Memory deficits have been extensively studied in TLE, but
      the presence of pre-existing temporal lobe abnormality has confounded studies on
      the relationship between memory dysfunction and seizure activity. Idiopathic
      generalised epilepsy (IGE) is characterised by primary generalised seizures and
      is found to occur in the absence of any macroscopic brain abnormalities. IGE is
      therefore ideal for investigations on the effects of seizure activity on memory
      and cognition. AIM AND METHODS: Magnetic resonance spectroscopy (MRS) and
      neuropsychological testing were used to investigate the relationship between
      epileptic seizures, memory performance and neuronal dysfunction in the temporal
      lobes of a group of patients with IGE. 30 patients and 15 healthy controls
      participated in the study. RESULTS: Patients with IGE were found to perform worse
      than controls on tests of speed of information processing, general cognitive
      performance and a range of memory tests, including face recognition, word
      recognition, verbal recall and complex figure recall. The performance of the
      patient group on the visual recognition and verbal recall sections of the Doors
      and People Test was found to correlate with MRS ratios of N-acetyl
      aspartate:choline and N-acetyl aspartate:creatine in the temporal lobes.
      CONCLUSION: This result supports the hypothesis that memory deficits in epilepsy
      may be due to neuronal dysfunction secondary to epileptic activity itself in the
      absence of any macroscopic lesions in the temporal lobes.

PMID- 16574727
TI  - Intrathecal IgM production at clinical onset correlates with a more severe
      disease course in multiple sclerosis.
AB  - The intrathecal synthesis of IgM, determined at clinical onset in patients with
      multiple sclerosis, was found to correlate with the degree of disability (as
      evaluated by means of the Expanded Disability Status Scale) reached 15 years
      later (p<0.001). Moreover, a significant inverse correlation was observed between
      the value of the IgM index and time to the first relapse (p<0.001) and the
      initiation of the progressive phase of the disease (p = 0.01). The prognostic
      value of IgM in the CSF is confirmed in previous reports as well as by our study.
      If these findings are confirmed in patients with multiple sclerosis in a larger
      series, a helpful biological marker for selecting patients for immunomodulatory
      treatments will be available to neurologists.

PMID- 16574728
TI  - The neurology of enteric disease.

PMID- 16574729
TI  - Cerebrospinal fluid findings in multiple sclerosis patients before, during and
      after pregnancy.

PMID- 16574730
TI  - A modified peripheral neuropathy scale: the Overall Neuropathy Limitations Scale.
AB  - A new peripheral neuropathy activities measure, the Overall Neuropathy
      Limitations Scale (ONLS), was derived by modifying the Overall Disability Sum
      Score (ODSS) slightly. Its inter-rater reliability was found to be high and its
      correlation with the ODSS (r = 0.97), 36-item Short Form Questionnaire Physical
      Component Summary Score, and participation and impairment measures was
      significant. Acceptable responsiveness (standardised response mean 0.76) was
      shown by the ONLS. The results obtained from the questionnaire agreed closely
      with those obtained from observation of the tasks on the ONLS, but were not
      equivalent. The simplicity of the ODSS is shared by the ONLS, but the ONLS has
      better content validity and less ceiling effect, which may make it more useful
      for clinical practice and research.

PMID- 16574731
TI  - Endothelial cell activation markers and delayed cerebral ischaemia in patients
      with subarachnoid haemorrhage.
AB  - BACKGROUND: Endothelial cell activation may be connected with the pathogenesis of
      delayed cerebral ischaemia (DCI) after subarachnoid haemorrhage (SAH). AIM: To
      assess the relationship between serial concentrations of circulating markers of
      endothelial cell activation (soluble intercellular adhesion molecule-1, soluble
      platelet selectin (sP-selectin), soluble endothelial selectin, ED1-fibronectin,
      Von Willebrand Factor (VWF) and VWF propeptide) and development of DCI. METHODS:
      687 blood samples were collected from 106 consecutive patients admitted within 72
      h after onset of SAH. Changes in levels were analysed in the last sample before
      and in the first sample after the onset of DCI (n = 30), and in subgroups with
      DCI occurring within 24 h after treatment of the aneurysm (n = 12) or unrelated
      to treatment of the aneurysm (n = 18). Patients without DCI (n = 56) served as
      controls. RESULTS: Concentrations of sP-selectin, but not of the other markers,
      were found to increase considerably after DCI unrelated to treatment of the
      aneurysm (increase 25 ng/ml, 95% CI 8 to 43), whereas they tended to decrease in
      the control patients without DCI (decrease 13 ng/ml, 95% CI -28 to 2.4). Surgery
      was found to profoundly influence the levels of the markers irrespective of the
      occurrence of DCI. CONCLUSION: The rise in sP-selectin level during DCI is
      suggested to be the result of platelet activation, as levels of the other markers
      of endothelial cell activation were not increased after DCI unrelated to
      treatment. Whether a causal role of platelet activation is implicated in the
      development of DCI should be determined in further studies in which the
      relationship between concentrations of markers and treatment is taken into
      account.

PMID- 16574732
TI  - Clinimetric properties of a walking scale in peripheral neuropathy.
AB  - Difficulty in walking is seen in many people with peripheral neuropathies, but
      walking ability is not comprehensively measured by commonly used outcome
      measures. The clinimetric properties of the 12-Item Multiple Sclerosis Walking
      Scale (MSWS-12, renamed the Walk-12) were investigated in 65 patients with
      peripheral neuropathies. Owing to its excellent internal consistency and
      reliability, and strong correlation with measures of physical and social function
      (r>0.8), the Walk-12 is recommended for measuring walking ability in peripheral
      neuropathies.

PMID- 16574733
TI  - Deep-brain stimulation: long-term analysis of complications caused by hardware
      and surgery--experiences from a single centre.
AB  - OBJECTIVE: To determine the surgery-related and hardware-related complications of
      deep-brain stimulation (DBS) at a single centre. METHODS: 262 consecutive
      patients (472 electrodes) operated for DBS in our department from February 1996
      to March 2003 were retrospectively analysed to document acute adverse events (30
      days postoperatively). The data of 180 of these patients were additionally
      revised to assess long-term complications (352 electrodes, mean follow-up 36.3
      (SD 20.8) months). RESULTS: The frequency of minor intraoperative complications
      was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological
      deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were
      registered as acute severe adverse events caused by surgery. Among minor acute
      complications were subcutaneous bleeding along the extension wire (1.2%) and
      haematoma at the pulse generator implantation site (1.2%). Skin infection caused
      by the implanted material was registered in 15 of 262 patients (5.7%). The
      infection rate during the first observation period was 1.5% (4/262 patients) and
      the late infection rate was 6.1% (11/180 patients). Partial or complete removal
      of the stimulation system was necessitated in 12 of 262 (4.6%) patients because
      of skin infection. During the long-term observation period, hardware-related
      problems were registered in 25 of 180 (13.9%) patients. CONCLUSIONS: Stereotactic
      implantation of electrodes for DBS, if performed with multiplanar three
      dimensional imaging and advanced treatment planning software, is a safe procedure
      with no mortality and low morbidity. The main causes for the patients' prolonged
      hospital stay and repeated surgery were wound infections and hardware-related
      complications.

PMID- 16574734
TI  - Evidence for white matter disruption in traumatic brain injury without
      macroscopic lesions.
AB  - BACKGROUND: Non-missile traumatic brain injury (nmTBI) without macroscopically
      detectable lesions often results in cognitive impairments that negatively affect
      daily life. AIM: To identify abnormal white matter projections in patients with
      nmTBI with cognitive impairments using diffusion tensor magnetic resonance
      imaging (DTI). METHODS: DTI scans of healthy controls were compared with those of
      23 patients with nmTBI who manifested cognitive impairments but no obvious
      neuroradiological lesions. DTI was comprised of fractional anisotropy analysis,
      which included voxel-based analysis and confirmatory study using regions of
      interest (ROI) techniques, and magnetic resonance tractography of the corpus
      callosum and fornix. RESULTS: A decline in fractional anisotropy around the genu,
      stem and splenium of the corpus callosum was shown by voxel-based analysis.
      Fractional anisotropy values of the genu (0.47), stem (0.48), and splenium of the
      corpus callosum (0.52), and the column of the fornix (0.51) were lower in
      patients with nmTBI than in healthy controls (0.58, 0.61, 0.62 and 0.61,
      respectively) according to the confirmatory study of ROIs. The white matter
      architecture in the corpus callosum and fornix of patients with nmTBI were seen
      to be coarser than in the controls in the individual magnetic resonance
      tractography. CONCLUSIONS: Disruption of the corpus callosum and fornix in
      patients with nmTBI without macroscopically detectable lesions is shown. DTI is
      sensitive enough to detect abnormal neural fibres related to cognitive
      dysfunction after nmTBI.

PMID- 16574735
TI  - A multicentre, randomised trial examining the effect of test procedures measuring
      emergence from post-traumatic amnesia.
AB  - BACKGROUND: Post-traumatic amnesia (PTA) tests that record different PTA
      durations in the same patient, thereby raising measurement accuracy issues, have
      been reported previously. A major problem lies in determining the end point of
      PTA. AIMS: To delineate areas of discrepancy in PTA tests and to provide
      independent verification for a criterion signalling emergence from PTA. METHODS:
      In a randomised design, two related PTA procedures were compared, one purportedly
      more difficult (Westmead PTA Scale, WPTAS) than the other (Modified Oxford PTA
      Scale, MOPTAS). Eighty two patients in the early stages of PTA were examined
      daily until emergence, by using the Galveston Orientation and Amnesia Test (GOAT)
      and the WPTAS/MOPTAS. A short battery of cognitive and behavioural measurements
      was made on three occasions: at the early stage of PTA (time 1), towards the end
      of PTA when the maximum score (12/12) was first obtained (time 2) and at the
      traditional criterion for emergence (scoring 12/12 for 3 consecutive days; time
      3). RESULTS: No significant difference was recorded in PTA duration between the
      MOPTAS and WPTAS. Both scales recorded longer PTA durations than the GOAT. By
      using Kaplan-Meier survival analyses, the WPTAS was found to show a more
      protracted pattern of emergence at the end stage of PTA than the MOPTAS. A time
      lag of > or = 1 week in the resolution of disorientation as compared with amnesia
      was observed in 59% cases. Significant improvements occurred on all independent
      measurements between time 1 and time 2, but on only 2 of 5 cognitive measurements
      between time 2 and time 3. CONCLUSIONS: Although no significant differences in
      the duration of PTA on the MOPTAS/WPTAS were recorded, emergence from the late
      stages of PTA occurred more promptly with the MOPTAS. The need for inclusion of
      both orientation and memory items in PTA tests is highlighted by the frequency of
      disorientation-amnesia dissociations. The patterns of results on the independent
      measures suggest that patients who are in PTA for > 4 weeks have probably emerged
      from PTA when they first score 12/12 on the MOPTAS/WPTAS, and this criterion can
      replace the traditional criterion.

PMID- 16574736
TI  - Axial rotation in Parkinson's disease.
AB  - AIMS: To investigate the ability of patients with Parkinson's disease to perform
      a rotation around the longitudinal axis of the body. Three questions were raised.
      Is body rotation impaired in Parkinson's disease? Is there a level of the
      kinematic chain from the head to the foot at which the impairment is more severe?
      Is the deficit related to the general slowness of movement in Parkinson's
      disease? METHODS: Kinematic data were recorded. The temporal organisation of body
      rotation during gait initiation was analysed in 10 patients with Parkinson's
      disease, who were all at an advanced stage of the disease and had all experienced
      falls and freezing during their daily life, and in five controls. The latency of
      the onset of the rotation of each segment was measured by taking the onset of the
      postural phase of step initiation as reference value. Locomotor variables were
      also analysed. RESULTS: Body rotation was found to be impaired in patients with
      Parkinson's disease, as the delay in the onset of the rotation of each segment is
      greater than that in controls. Moreover, a specific uncoupling in the onset of
      shoulder and pelvis segment rotation was seen in patients. This impairment of
      rotation is not related only to the general slowness of movements. CONCLUSION:
      Patients with Parkinson's disease were found to have an impairment of posturo
      kinetic coordination and impaired capacity to exert appropriate ground reaction
      forces to orient the pelvis in space.

PMID- 16574737
TI  - Bip is a molecular link between the phase I and phase II estrogenic responses in
      uterus.
AB  - Uterine estrogenic actions are biphasic, early (phase I) and late (phase II)
      responses. However, the molecular linkage between these phases is not known.
      Although certain phase I responses are considered estrogen receptor (ER)alpha and
      ERbeta independent, the phase II responses are ERalpha dependent. We previously
      observed that among several genes Bip is induced by estrogen in the mouse uterus
      in an ER-independent manner as a phase I response. Bip is a member of the
      chaperone family and plays roles in protein processing and confers cellular
      protection. However, its role in estrogen-dependent uterine biology is unknown.
      We show here a new function of Bip in regulating estrogen signaling in the
      uterus. Bip, induced during the phase I responses, molecularly interacts with
      ERalpha required for estrogen-mediated phase II growth responses. Utilizing in
      vivo and in vitro model systems, we found that adenovirus-driven suppression of
      Bip antagonizes ERalpha-mediated uterine gene transcription. Importantly, down
      regulation of Bip compromises estrogen-dependent phase II growth responses with
      sustained phase I responses. In conclusion, Bip is critical for coordinating
      estrogen-elicited biphasic responses and serves as a molecular link between
      ERalpha-independent and -dependent estrogenic responses in the uterus.

PMID- 16574738
TI  - The human transient receptor potential vanilloid type 6 distal promoter contains
      multiple vitamin D receptor binding sites that mediate activation by 1,25
      dihydroxyvitamin D3 in intestinal cells.
AB  - Transient receptor potential vanilloid type 6 (TRPV6) (ECAC2, CaT1) is the major
      ion channel in intestinal epithelial cell membranes responsible for calcium
      entry. Its expression is actively regulated at the transcriptional level by 1,25
      dihydroxyvitamin D3 [1,25-(OH)2D3]. In this report, we identify mechanisms
      integral to the regulation of TRPV6 by 1,25-(OH)2D3. Based upon the hormonal
      responsiveness of a 7-kb TRPV6 promoter fragment in intestinal cell lines, we
      used a chromatin immunoprecipitation (ChIP) scanning method to search for
      possible vitamin D receptor (VDR) and retinoid X receptor (RXR) regulatory
      regions within the TRPV6 locus. VDR/RXR binding was broad, ranging from -1.2 to 
      5.5 kb relative to the start site of TRPV6 transcription. These results were
      consistent with an in silico analysis that revealed putative regulatory elements
      (VDREs) located at -1.2, -2.1, -3.5, -4.3, and -5.5 kb. Despite the ChIP
      analyses, only regions of the TRPV6 gene that contained putative elements at -2.1
      and -4.3 kb transferred 1,25-(OH)2D3 response to a heterologous promoter. Further
      study revealed that each of these two active regions contained composite VDREs
      comprised of two separate regulatory elements. Mutagenesis of the VDREs within
      the -2.1- and -4.3-kb region and the VDRE at -1.2 kb abrogated all response to
      1,25-(OH)2D3 when examined within the natural TRPV6 promoter. A final ChIP assay
      revealed that VDR/RXR heterodimer binding to the TRPV6 gene was accompanied by
      both the recruitment of steroid receptor coactivator 1 as well as a broad change
      in histone 4 acetylation. These studies identify a mechanism by which 1,25
      (OH)2D3 regulates the expression of TRPV6 in human intestinal cells.

PMID- 16574740
TI  - Activation of the blue opsin gene in cone photoreceptor development by retinoid
      related orphan receptor beta.
AB  - Color vision requires the expression of opsin photopigments with different
      wavelength sensitivities in retinal cone photoreceptors. The basic color visual
      system of mammals is dichromatic, involving differential expression in the cone
      population of two opsins with sensitivity to short (S, blue) or medium (M, green)
      wavelengths. However, little is known of the factors that directly activate these
      opsin genes and thereby contribute to the S or M opsin identity of the cone. We
      report that the orphan nuclear receptor RORbeta (retinoid-related orphan receptor
      beta) activates the S opsin gene (Opn1sw) through binding sites upstream of the
      gene. RORbeta lacks a known physiological ligand and activates the Opn1sw
      promoter modestly alone but strongly in synergy with the retinal cone-rod
      homeobox factor (CRX), suggesting a cooperative means of enhancing RORbeta
      activity. Comparison of wild-type and mutant lacZ reporter transgenes showed that
      the RORbeta-binding sites in Opn1sw are required for expression in mouse retina.
      RORbeta-deficient mice fail to induce S opsin appropriately during postnatal cone
      development. Photoreceptors in these mice also lack outer segments, indicating
      additional functions for RORbeta in photoreceptor morphological maturation. The
      results identify Opn1sw as a target gene for RORbeta and suggest a key role for
      RORbeta in regulating opsin expression in the color visual system.

PMID- 16574739
TI  - Regulation of insulin receptor substrate 1 pleckstrin homology domain by protein
      kinase C: role of serine 24 phosphorylation.
AB  - Phosphorylation of insulin receptor substrate (IRS) proteins on serine residues
      is an important posttranslational modification that is linked to insulin
      resistance. Several phosphoserine sites on IRS1 have been identified; the
      majority are located proximal to the phosphotryosine-binding domain or near key
      receptor tyrosine kinase substrate- and/or Src-homology 2 domain-binding sites.
      Here we report on the characterization of a serine phosphorylation site in the N
      terminal pleckstrin homology (PH) domain of IRS1. Bioinformatic tools identify
      serine 24 (Ser24) as a putative substrate site for the protein kinase C (PKC)
      family of serine kinases. We demonstrate that this site is indeed a bona fide
      substrate for conventional PKC. In vivo, IRS-1 is also phosphorylated on Ser24
      after phorbol 12-myristate 13-acetate treatment of cells, and isoform-selective
      inhibitor studies suggest the involvement of PKCalpha. By comparing the
      pharmacological characteristics of phorbol 12-myristate 13-acetate-stimulated
      Ser24 phosphorylation with phosphorylation at two other sites previously linked
      to PKC activity (Ser307 and Ser612), we show that PKCalpha is likely to be
      directly involved in Ser24 phosphorylation, but indirectly involved in Ser307 and
      Ser612 phosphorylation. Using Ser24Asp IRS-1 mutants to mimic the phosphorylated
      residue, we demonstrate that the phosphorylation status of Ser24 does play an
      important role in regulating phosphoinositide binding to, and the intracellular
      localization of, the IRS1-PH domain, which can ultimately impinge on insulin
      stimulated glucose uptake. Hence we provide evidence that IRS1-PH domain function
      is important for normal insulin signaling and is regulated by serine
      phosphorylation in a manner that could contribute to insulin resistance.

PMID- 16574741
TI  - Linking ligand-induced alterations in androgen receptor structure to differential
      gene expression: a first step in the rational design of selective androgen
      receptor modulators.
AB  - We have previously identified a family of novel androgen receptor (AR) ligands
      that, upon binding, enable AR to adopt structures distinct from that observed in
      the presence of canonical agonists. In this report, we describe the use of these
      compounds to establish a relationship between AR structure and biological
      activity with a view to defining a rational approach with which to identify
      useful selective AR modulators. To this end, we used combinatorial peptide phage
      display coupled with molecular dynamic structure analysis to identify the
      surfaces on AR that are exposed specifically in the presence of selected AR
      ligands. Subsequently, we used a DNA microarray analysis to demonstrate that
      differently conformed receptors facilitate distinct patterns of gene expression
      in LNCaP cells. Interestingly, we observed a complete overlap in the identity of
      genes expressed after treatment with mechanistically distinct AR ligands.
      However, it was differences in the kinetics of gene regulation that distinguished
      these compounds. Follow-up studies, in cell-based assays of AR action, confirmed
      the importance of these alterations in gene expression. Together, these studies
      demonstrate an important link between AR structure, gene expression, and
      biological outcome. This relationship provides a firm underpinning for mechanism
      based screens aimed at identifying SARMs with useful clinical profiles.

PMID- 16574742
TI  - Calcitonin increases tumorigenicity of prostate cancer cells: evidence for the
      role of protein kinase A and urokinase-type plasminogen receptor.
AB  - The expression of human (h) calcitonin (CT) and its receptor (CTR) is localized
      to basal epithelium in benign prostates but is distributed in whole epithelium of
      malignant prostates. Moreover, the abundance of hCT and CTR mRNA in primary
      prostate tumors positively correlates with the tumor grade. We tested the
      hypothesis that the modulation of endogenous hCT expression of prostate cancer
      (PC) cell lines alters their oncogenicity. The effect of modulation of hCT
      expression on oncogenic characteristics was examined in LNCaP and PC-3M cell
      lines. The endogenous hCT expression was modulated using either constitutively
      active expression vector containing hCT cDNA or anti-hCT hammerhead ribozymes.
      The changes in the oncogenicity of cell sublines was assessed with cell
      proliferation assays, invasion assays, colony formation assays, and in vivo
      growth in athymic nude mice. Up-regulation of hCT in PC-3M cells and or enforced
      hCT expression in LNCaP cells dramatically enhanced their oncogenic
      characteristics. In contrast, the down-regulation of hCT in PC-3M cells led to a
      dramatic decline in their oncogenicity. These results, when combined with our
      other results, that the expression of hCT in primary PCs increase with tumor
      grade, suggest an important role for hCT in the progression of PC to a metastatic
      phenotype.

PMID- 16574743
TI  - Identification of follicle-stimulating hormone-selective beta-strands in the N
      terminal hormone-binding exodomain of human gonadotropin receptors.
AB  - Glycoprotein hormone receptors contain large N-terminal extracellular domains
      (ECDs) that distinguish these receptors from most other G protein-coupled
      receptors. Each glycoprotein hormone receptor ECD consists of a curved leucine
      rich repeat domain flanked by N- and C-terminal cysteine-rich regions.
      Selectivity of the different glycoprotein hormone receptors for their cognate
      hormones is exclusively determined by their ECDs and, in particular, their
      leucine-rich repeat domain. To identify human (h)FSH-selective determinants we
      used a gain-of-function mutagenesis strategy in which beta-strands of the hLH
      receptor (hLH-R) were substituted with their hFSH receptor (hFSH-R) counterparts.
      Introduction of hFSH-R beta-strand 1 into hLH-R conferred responsiveness to hFSH,
      whereas hLH-R mutants harboring one of the other hFSH-R beta-strands displayed
      none or very limited sensitivity to hFSH. However, combined substitution of hFSH
      R beta-strand 1 and some of the other hFSH-R beta-strands further increased the
      sensitivity of the mutant hLH-R to hFSH. The apparent contribution of multiple
      hFSH-R beta-strands in providing a selective hormone binding interface
      corresponds well with their position in relation to hFSH as recently determined
      in the crystal structure of hFSH in complex with part of the hFSH-R ECD.

PMID- 16574744
TI  - Soluble mimics of the cytoplasmic face of the human V1-vascular vasopressin
      receptor bind arrestin2 and calmodulin.
AB  - Signal transduction by G protein-coupled receptors (GPCRs) is mediated by
      interactions between intracellular proteins and exposed motifs on the cytoplasmic
      face of these receptors. Arrestins bind to GPCRs and modulate receptor function
      either by interfering with heterotrimeric G protein signaling or by serving as
      signaling adaptors themselves. Calmodulin interacts with GPCRs triggering a
      calcium response. We have studied the interaction of arrestin2 and calmodulin
      with intracellular elements of the human V1-vascular vasopressin receptor (hV1R).
      For this purpose, we designed, expressed, and purified soluble fusion proteins
      with the maltose-binding protein (MBP) from Escherichia coli that mimic the
      intracellular surface of the hV1R. These MBP fusion proteins bind arrestin2 and
      calmodulin with affinities in the micromolar range. A different series of soluble
      receptor analogs, named vasopressin receptor 1 elements on a soluble scaffold
      (V1ROSS) proteins, consist of the third intracellular loop and/or the C-terminal
      segment of the hV1R receptor juxtaposed on the surface of the MBP. V1ROSS
      proteins bind calmodulin and a truncated, phosphorylation-independent form of
      arrestin2 more tightly than the corresponding linear fusion proteins. Thus,
      embedding receptor loops within the three-dimensional structure of the MBP yields
      a better representation of the active conformation of these receptor loops than
      linear receptor peptides fused onto the C terminus of the MBP. V1ROSS proteins
      provide a valuable tool to study receptor interactions because they are more
      amenable to structural analysis than the native membrane receptor. These findings
      set the stage for the detailed structural analysis of these protein-protein
      interactions that are important for understanding the mechanism of signaling.

PMID- 16574745
TI  - A perspective on the use of iTRAQ reagent technology for protein complex and
      profiling studies.
AB  - Proteomic research includes the characterization of protein mixtures in order to
      understand complex biological systems and determine relationships between
      proteins, their function, and protein-protein interactions. Often the goal of
      such research is to monitor changes of proteins in perturbed systems, a type of
      study referred to as differential expression analysis. To perform these studies
      requires the ability to execute some type of differential comparison of a given
      protein state in reference to some type of a control. The iTRAQ reagents are a
      set of isobaric reagents which are amine specific and allow for the
      identification and quantitation of up to four different samples simultaneously.
      The amine specificity of these reagents makes most peptides in a sample amenable
      to this labeling strategy with no loss of information from samples involving post
      translational modifications, such as the scrutiny of signal transduction pathways
      that often involve phosphorylation phenomena. In addition, the multiplexing
      capacity of these reagents allows for information replication within certain LC
      MS/MS experimental regimes, providing additional statistical validation within
      any given experiment. The results presented herein demonstrate a few examples of
      the wide variety of quantitative information that can be realized when
      undertaking such experimental approaches. These include temporal analysis of drug
      induced-protein expression, discovery and elucidation of disease markers, and
      protein-protein interactions in multi-protein complexes.

PMID- 16574746
TI  - Sequencing covalent modifications of membrane proteins.
AB  - A number of strategies have successfully extended plant proteomics into the
      bilayer domain. Important benefits can be afforded by including a well-resolved
      intact protein mass spectrum alongside peptide identification experiments; recent
      studies of thylakoid membranes have yielded new information on the primary
      structure and covalent post-translational modification of many of the integral
      proteins. Intact mass proteomics is advancing through the development of core
      technologies in separations and mass spectrometry, with the goal of providing
      comprehensive primary structure coverage that includes transmembrane domains with
      reliable measurements of protein abundance and turnover. To address the
      limitations associated with separation technologies such as 2D-gel
      electrophoresis, alternative systems are being investigated and 2D-liquid
      chromatography of thylakoid membrane proteins, using both denaturing and non
      denaturing first dimensions, has been successful, extending separation space and
      providing intact protein solutions for electrospray-ionization mass spectrometry
      and top-down proteomics. High-resolution conventional, and Fourier-transform,
      mass spectrometry is bringing increasing resolution to tandem mass spectrometry
      allowing for 'top-down' mass spectrometry of intact proteins. Thus the core
      chromatographic technologies already developed for intact mass proteomics of
      integral membrane proteins also allow their 'top-down' analysis. Thylakoid
      membrane proteins with one and two transmembrane helices have been analysed
      demonstrating the ability of collision-activated dissociation (CAD) to sequence
      through transmembrane domains. When analysed by top-down proteomics, the small
      subunits of the cytochrome b6f complex from Arabidopsis thylakoids reveal novel
      post-transcriptional/translational modifications including the presence of
      glutamic acid at position 2 of PetL instead of the proline residue predicted from
      the gene sequence.

PMID- 16574747
TI  - Relative and absolute quantitative shotgun proteomics: targeting low-abundance
      proteins in Arabidopsis thaliana.
AB  - The plant system is a highly dynamic structure on all molecular levels,
      transcripts, proteins, and metabolites. Thus, protein analysis has to cope with a
      highly dynamic range of concentrations. A severe problem is the detection of low
      abundance proteins in the presence of housekeeping proteins. Basically three
      approaches are facilitated to measure protein abundance in a comprehensive
      manner: 2DE and one- or multi-dimensional shotgun proteomics, with or without
      stable-isotope labelling. These comparative techniques allow for the
      identification of altered protein levels compared with a reference state.
      However, they are limited to the analysis of medium/high-abundance proteins.
      Using stable-isotope dilution techniques it is possible to target the
      quantitative analysis to low-abundance proteins and to measure absolute
      concentrations of proteins. Based on multi-dimensional non-gel shotgun proteomics
      in Arabidopis thaliana, a list of tryptic peptides comprising >1000 proteins was
      generated. A strategy for quantitative plant proteomics is proposed using this
      master-list for selecting signature peptides of proteins. To prove the concept, a
      liquid chromatography-high-resolution triple quadrupole multiple reaction
      monitoring-mass spectrometry technique is described to determine the absolute
      amount of a low-abundance sucrose synthase isoform out of an ultra-complex A.
      thaliana protein extract.

PMID- 16574748
TI  - The heat shock response of Synechocystis sp. PCC 6803 analysed by transcriptomics
      and proteomics.
AB  - When cells of the cyanobacterium Synechocystis sp. PCC 6803 are exposed to high
      temperature they perceive changes in the growth conditions and regulate the
      expression of genes and synthesize heat-inducible proteins as a response to the
      heat stress. DNA microarray analysis revealed that genes for chaperonins and
      proteases, such as groESL1, groEL2, htpG, hspA, and clpB1 were transiently
      induced after incubation of the cells at 44 degrees C for 20 min. Quantitative
      two-dimensional gel electrophoresis revealed that the levels of these chaperonins
      and proteases were elevated after incubation of cells at 44 degrees C for 60 min.
      These findings indicated that levels of the mRNAs and proteins of chaperonins
      were well correlated in the cells of Synechocystis. However, the level of
      elongation factors are mainly regulated at the protein level. These results
      indicated that acclimation to the heat-shock conditions might be governed by
      transcriptional and translational regulation in Synechocystis.

PMID- 16574749
TI  - Proteome analysis of cold stress response in Arabidopsis thaliana using DIGE
      technology.
AB  - A proteome study based on 2-D gel electrophoresis was performed in order to
      analyse the cold-stress response of Arabidopsis plants. The emphasis was to
      monitor the overall changes in the protein complement after prolonged exposure
      rather than short-term responses. Two different temperature regimes were used (6
      degrees C and 10 degrees C) and plants were exposed to cold-stress exposure for 1
      week. Protein patterns were also monitored after re-shifting plants to control
      conditions for a further week. To monitor gradual changes in the response to the
      two cold-stress conditions, the analysis was performed with DIGE technology with
      the inclusion of an internal standard. In the experiments using 6 degrees C, 22
      spots with at least 2-fold altered expression were found; among them 18 were
      increased and four were decreased. When plants were exposed to 10 degrees C, 18
      of these 22 spots still showed a 2-fold change; however, the alterations were, in
      general, more moderate than observed under 6 degrees C. Spot identification was
      performed by MALDI-TOF and ESI-MS/MS. Many of the proteins identified have
      previously been described in the context of cold-stress responses, indicating the
      validity of this proteome approach for further in-depth studies.

PMID- 16574750
TI  - Identification and functional analysis of candidate genes regulating mesenchymal
      stem cell self-renewal and multipotency.
AB  - Adult human mesenchymal stem cells (hMSCs) possess multilineage differentiation
      potential, and differentiated hMSCs have recently been shown to have the ability
      to transdifferentiate into other lineages. However, the molecular signature of
      hMSCs is not well-known, and the mechanisms regulating their self-renewal,
      differentiation, and transdifferentiation are not completely understood. In this
      study, we demonstrate that fully differentiated hMSCs could dedifferentiate, a
      likely critical step for transdifferentiation. By comparing the global gene
      expression profiles of undifferentiated, differentiated, and dedifferentiation
      cells in three mesenchymal lineages (osteogenesis, chondrogenesis, and
      adipogenesis), we identified a number of "stemness" and "differentiation" genes
      that might be essential to maintain adult stem cell multipotency as well as to
      drive lineage-specific commitment. These genes include those that encode cell
      surface molecules, as well as components of signaling pathways. These genes may
      be valuable for developing methods to isolate, enrich, and purify homogeneous
      population of hMSCs and/or maintain and propagate hMSCs as well as guide or
      regulate their differentiation for gene and cell-based therapy. Using small
      interfering RNA gene inactivation, we demonstrate that five genes (actin filament
      associated protein, frizzled 7, dickkopf 3, protein tyrosine phosphatase receptor
      F, and RAB3B) promote cell survival without altering cell proliferation, as well
      as exhibiting different effects on the commitment of hMSCs into multiple
      mesenchymal lineages.

PMID- 16574751
TI  - Regeneration and transdifferentiation potential of muscle-derived stem cells
      propagated as myospheres.
AB  - We have isolated from mouse skeletal muscle a subpopulation of slow adherent
      myogenic cells that can proliferate for at least several months as suspended
      clusters of cells (myospheres). In the appropriate conditions, the myospheres
      adhere to the plate, spread out, and form a monolayer of MyoD(+) cells. Unlike
      previously described myogenic cell lines, most of the myosphere cells
      differentiate, without cell fusion, into thin mononucleated contractile fibers,
      which express myogenin and skeletal muscle myosin heavy chain. The presence of
      Pax-7 in a significant proportion of these cells suggests that they originate
      from satellite cells. The addition of leukemia inhibitory factor to the growth
      medium of the myospheres enhances proliferation and dramatically increases the
      proportion of cells expressing Sca-1, which is expressed by several types of stem
      cells. The capacity of myosphere cells to transdifferentiate to other mesodermal
      cell lineages was examined. Exposure of cloned myosphere cells to bone
      morphogenetic protein resulted in suppression of myogenic differentiation and
      induction of osteogenic markers such as alkaline phosphatase and osteocalcin.
      These cells also sporadically differentiated to adipocytes. Myosphere cells could
      not, so far, be induced to transdifferentiate to hematopoietic cells. When
      inoculated into injured muscle, myosphere-derived cells participated in
      regeneration, forming multinucleated cross-striated mature fibers. This suggests
      a potential medical application.

PMID- 16574752
TI  - Transplanted embryonic stem cells successfully survive, proliferate, and migrate
      to damaged regions of the mouse brain.
AB  - An understanding of feasibility of implanting embryonic stem cells (ESCs), their
      behavior of migration in response to lesions induced in brain tissues, and the
      mechanism of their in vivo differentiation into neighboring neural cells is
      essential for developing and refining ESC transplantation strategies for
      repairing damages in the nervous system, as well as for understanding the
      molecular mechanism underlying neurogenesis. We hypothesized that damaged neural
      tissues offer a niche to which injected ESCs can migrate and differentiate into
      the neural cells. We inflicted damage in the murine (C57BL/6) brain by injecting
      phosphate-buffered saline into the left frontal and right caudal regions and
      confirmed neural damage by histochemistry. Enhanced yellow fluorescent protein
      expressing ESCs were injected into the nondamaged left caudal portion of the
      brain. Using immunohistochemistry and fluorescent microscopy, we observed
      migration of ESCs from the injection site (left caudal) to the damaged site
      (right caudal and left frontal). Survival of the injected ESCs was confirmed by
      the real-time polymerase chain reaction analysis of stemness genes such as Oct4,
      Sox2, and FGF4. The portions of the damaged neural tissues containing ESCs
      demonstrated a fourfold increase in expression of these genes after 1 week of
      injection in comparison with the noninjected ESC murine brain, suggesting
      proliferation. An increased level of platelet-derived growth factor receptor
      demonstrated that ESCs responded to damaged neural tissues, migrated to the
      damaged site of the brain, and proliferated. These results demonstrate that
      undifferentiated ESCs migrate to the damaged regions of brain tissue, engraft,
      and proliferate. Thus, damaged brain tissue provides a niche that attracts ESCs
      to migrate and proliferate.

PMID- 16574753
TI  - Gene expression profiles in murine hematopoietic stem cells revisited: analysis
      of cDNA libraries reveals high levels of translational and metabolic activities.
AB  - Gene expression studies from hematopoietic stem cell (HSC) populations purified
      to variable degrees have defined a set of stemness genes. Unexpectedly, results
      also hinted toward a HSC chromatin poised in a wide-open state. With the aim of
      providing a robust tool for further studies into the molecular biology of HSCs,
      the studies herein describe the construction and comparative molecular analysis
      of lambda-phage cDNA libraries from highly purified HSCs that retained their long
      term repopulating activities (long-term HSCs [LT-HSCs]) and from short-term
      repopulating HSCs that were largely depleted of these activities. Microarray
      analysis of the libraries confirmed the previous results but also revealed an
      unforeseen preferential expression of translation- and metabolism-associated
      genes in the LT-HSCs. Therefore, these data indicate that HSCs are quiescent only
      in regard of proliferative activities but are in a state of readiness to provide
      the metabolic and translational activities required after induction of
      proliferation and exit from the HSC pool.

PMID- 16574754
TI  - Defining the conditions for the generation of melanocytes from human embryonic
      stem cells.
AB  - Because of their undifferentiated nature, human embryonic stem cells (hESCs) are
      an ideal model system for studying both normal human development and the
      processes that underlie disease. In the current study, we describe an efficient
      method for differentiating hESCs into a melanocyte population within 4-6 weeks
      using three growth factors: Wnt3a, endothelin-3, and stem cell factor. The hESC
      derived melanocytes expressed melanocyte markers (such as microphthalmia
      associated transcription factor and tyrosinase), developed melanosomes, and
      produced melanin. They retained the melanocyte phenotype during long-term cell
      culture (>90 days) and, when incorporated into human reconstructed skin, homed to
      the appropriate location along the basement membrane in the same manner as
      epidermis-derived melanocytes. They maintained a stable phenotype even after
      grafting of the reconstructs to immunodeficient mice. Over time in culture, the
      hESC-derived melanocytes lost expression of telomerase and underwent senescence.
      In summary, we have shown for the first time the differentiation of hESCs into
      melanocytes. This method provides a novel in vitro system for studying the
      development biology of human melanocytes.

PMID- 16574755
TI  - Gap junctions and connexon hemichannels in human embryonic stem cells.
AB  - Intercellular communication via gap junctions is thought to play an important
      role in embryonic cell survival and differentiation. Classical studies
      demonstrated both dye and electrical coupling of cells in the inner cell mass of
      mouse embryos, as well as the development of restrictions against coupling
      between cells of the inner cell mass and surrounding trophectoderm. Here we
      demonstrate extensive gap junctional communication between human embryonic stem
      (ES) cells, the pluripotent cells isolated from the inner cell mass of
      preimplantation blastocysts. Human ES cells maintained in vitro expressed RNA for
      18 of the 20 known connexins; only connexin 40.1 (Cx40.1) and Cx50 were not
      detected by reverse transcription-polymerase chain reaction. Cx40, Cx43, and Cx45
      were visualized by immunofluorescence at points of contact between adjacent
      cells. Electron microscopy confirmed that neighboring cells formed zones of tight
      membrane apposition characteristic of gap junctions. Fluorescent dye injections
      demonstrated extensive coupling within human ES cell colonies growing on mouse
      embryonic fibroblast (MEF) feeder cells, whereas dye coupling between human ES
      cells and adjacent MEFs was extremely rare. Physiological recordings demonstrated
      electrical and dye coupling between human ES cells in feeder-free monolayers and
      between isolated human ES cell pairs. Octanol, 18-alpha-glycyrrhetinic acid, and
      arylaminobenzoates inhibited transjunctional currents. Dye uptake studies on
      human ES cell monolayers and recordings from solitary human ES cells gave
      evidence for the surface expression of connexon hemichannels. Human ES cells
      provide a unique system for the study of human connexin proteins and their
      potential functions in cellular differentiation and the maintenance of
      pluripotency.

PMID- 16574756
TI  - HPLC method for 25-hydroxyvitamin D measurement: comparison with contemporary
      assays.
AB  - BACKGROUND: The concentration of 25-hydroxyvitamin D [25(OH)D] in serum has been
      designated the functional indicator of vitamin D (VitD) nutritional status.
      Unfortunately, variability among 25(OH)D assays limits clinician ability to
      monitor VitD status, supplementation, and toxicity. METHODS: We developed an HPLC
      method that selectively measures 25-hydroxyvitamin D2 [25(OH)D2] and D3
      [25(OH)D3] and compared this assay with a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method, a competitive protein-binding assay (CPBA) on the
      Nichols Advantage platform, and an RIA from Diasorin. RESULTS: For the new HPLC
      assay, between-run CVs were 2.6%-4.9% for 25(OH)D3 and 3.2%-13% for 25(OH)D2;
      recoveries were 95%-102%; and the assay was linear from 5 microg/L to at least
      200 microg/L. Comparison data were as follows: for HPLC vs LC-MS/MS, y = 1.01x -
      4.82 microg/L (Sy/x = 4.93 microg/L; r = 0.996) for 25(OH)D3, and y = 0.902x -
      0.566 microg/L (Sy/x = 2.56 microg/L; r = 0.9965 for 25(OH)D2; for HPLC vs
      Diasorin RIA, y = 0.709x - 5.86 microg/L (Sy/x = 7.35 microg/L; r = 0.7509); and
      for HPLC vs Nichols Advantage CPBA, y = 1.00x - 3.60 microg/L (Sy/x = 32.7
      microg/L; r = 0.6823). CONCLUSIONS: The new HPLC method is reliable, robust, and
      has advantages compared with the Nichols Advantage CPBA and the Diasorin RIA. The
      Nichols Advantage CPBA overestimated or underestimated 25(OH)D concentrations
      predicated on the prevailing metabolite present in patients' sera.

PMID- 16574757
TI  - Peptide nucleic acid-based in situ hybridization assay for detection of
      parvovirus B19 nucleic acids.
AB  - BACKGROUND: Peptide nucleic acid (PNA) molecules are known to bind complementary
      nucleic acid sequences with a much stronger affinity and with more stable binding
      than DNA or RNA molecules. We chose parvovirus B19, which is diagnosed by
      detection of nucleic acids by in situ hybridization assay (ISH) and/or PCR, as an
      experimental model to develop an ISH assay that uses biotinylated PNA probes to
      detect viral genome in clinical specimens. METHODS: We first optimized the PNA
      ISH assay on B19-infected and mock-infected UT-7/EpoS1 cells and then tested the
      assay on archival B19 specimens and on consecutive specimens. All data were
      compared with data obtained with a standardized DNA-based ISH assay and confirmed
      by a PCR-ELISA. RESULTS: PNA-ISH detected B19 genome in a higher number of B19
      infected UT-7/EpoS1 cells and with a more defined localization of viral nucleic
      acids than the standardized DNA-ISH assay. Moreover, PNA-ISH was able to detect
      B19 genome in all positive archival samples, whereas DNA-ISH failed in 5 samples.
      PNA-ISH detected more positive samples than DNA-ISH when consecutive specimens
      were analyzed, and a close agreement was found with PCR-ELISA results.
      CONCLUSIONS: The PNA-ISH assay had sensitivity and specificity comparable to a
      PCR assay and was more practical and quicker to perform than standard
      hybridization assays. The assay may be a suitable diagnostic test for the
      detection of viral nucleic acids in clinical specimens.

PMID- 16574758
TI  - Anti-cardiolipin antibodies and overall survival in a large cohort: preliminary
      report.
AB  - BACKGROUND: Anti-cardiolipin antibodies have been associated with both arterial
      and venous thrombosis, but their overall impact on all-cause or vascular
      mortality is unknown. In this study, we evaluated the influence of anti
      cardiolipin antibodies on all-cause and vascular mortality. METHODS: All
      individuals who fulfilled the inclusion criteria (completeness of data, no
      admission from an intensive care unit, unique identification with name and date
      of birth) and whose anti-cardiolipin antibodies were measured between October
      2002 and February 2004 were included in this study (n = 4756; 64% female; median
      age, 46 years). Death/survival and cause of death were obtained from the Austrian
      Death Registry. The median observation period was 1.5 years, and the study
      comprised 7189 person-years. RESULTS: During the study period, 184 patients
      (3.9%) died. There were no associations between either anti-cardiolipin IgM or
      IgG antibodies and both vascular death and noncancer mortality as outcome
      variables in a Cox regression analysis adjusted for age and sex. In contrast, the
      risk of cancer-related mortality was increased 2.6-fold. CONCLUSIONS: Anti
      cardiolipin antibodies are associated with cancer mortality, likely as an
      epiphenomenon of malignancy, but they are not predictive of vascular mortality or
      noncancer mortality. Hence, although a clear association between anti-cardiolipin
      antibodies and (mostly nonfatal) vascular events has been described in the
      literature, our data indicate that this finding is not necessarily associated
      with an increase in vascular mortality.

PMID- 16574759
TI  - Frequency of thrombophilia-related genetic variations in patients with idiopathic
      pulmonary embolism in an urban emergency department.
AB  - BACKGROUND: The frequency of the thrombophilic genetic variants factor V Leiden
      (FVL) G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase
      (MTHFR) C677T in acutely symptomatic ambulatory patients with idiopathic
      pulmonary embolism (PE) has not been measured. METHODS: This prospective case
      control study included patients presenting to urban emergency departments (EDs)
      with chest pain or shortness of breath. Cases were classified as idiopathic PE
      (49 patients with PE, but without overt risk factors for thrombosis). Control
      groups included (a) patients with nonidiopathic PE (152 patients with PE and risk
      factors); (b) patients in whom PE was excluded (91 patients who had PE ruled out
      with a structured protocol, including follow-up); and (c) patients in whom PE was
      not suspected (193 patients without a workup for PE, who were free of PE on
      follow-up). Blood DNA extracts were analyzed by PCR and restriction fragment
      length polymorphism analysis for the FVL, prothrombin, and MTHFR sequence
      variations. RESULTS: Either the FVL or prothrombin variant was found in 10% (95%
      confidence interval, 3%-22%) of patients with idiopathic PE compared with 13% (8%
      20%) of nonidiopathic PE, 2% (5%-14%) of PE excluded, and 9% (5%-14%) of PE not
      suspected patients. Patients with idiopathic PE tended to have a higher frequency
      of homozygous MTHFR sequence variants, but mean (SD) plasma homocysteine
      concentrations were not increased [15.6 (5.4) micromol/L vs 12.8 (4.6) micromol/L
      for homozygous, and wild-type, respectively; P = 0.40]. CONCLUSIONS: The
      frequency of either the FVL or prothrombin sequence variant was not increased in
      idiopathic PE patients compared with nonidiopathic PE patients or patients who
      had PE excluded. These data suggest that genotyping to detect idiopathic PE would
      have limited clinical utility in the urban ED setting.

PMID- 16574760
TI  - Quantification of fragments of human serum inter-alpha-trypsin inhibitor heavy
      chain 4 by a surface-enhanced laser desorption/ionization-based immunoassay.
AB  - BACKGROUND: Several proteolytically derived fragments from the proline-rich
      region (PRR) of human inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) have
      been identified by surface-enhanced or matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS or MALDI-TOF
      MS) as potential disease markers. METHODS: Previously, we developed a SELDI-based
      immunoassay that can simultaneously distinguish and quantify multiple
      isoforms/variants of a protein/peptide of interest. In this study, we used this
      high-throughput approach to quantify and characterize the extensive fragmentation
      within the PRR of human serum ITIH4 and determined its association with different
      disease conditions. The ITIH4-related fragments were first immunocaptured by use
      of beads coupled with peptide-specific antibodies. The eluates were then studied
      by SELDI-TOF-MS. In addition, freshly collected and immediately processed serum
      and plasma samples were used to analyze the ex vivo stability of these ITIH4
      fragments. RESULTS: Human serum ITIH4 was shown to be extensively proteolytically
      processed within the PRR, and its fragmentation patterns were closely associated
      with different disease conditions. Fragmentation patterns were generally
      consistent with cleavages by endoprotease followed by exoprotease actions.
      Observed fragments changed little under different assay conditions or blood
      collection and processing procedures. CONCLUSIONS: The fragmentation patterns
      within the PRR of human serum ITIH4 are associated with different disease
      conditions and may hold important diagnostic information. These fragmentation
      patterns could be useful as potential biomarkers for detection and classification
      of cancer.

PMID- 16574761
TI  - Quantitative analysis of SNRPN(correction of SRNPN) gene methylation by
      pyrosequencing as a diagnostic test for Prader-Willi syndrome and Angelman
      syndrome.
AB  - BACKGROUND: Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are 2 distinct
      neurodevelopmental disorders caused primarily by deficiency of specific parental
      contributions at an imprinted domain within the chromosomal region 15q11.2-13. In
      most cases, lack of paternal contribution leads to PWS either by paternal
      deletion (approximately 70%) or maternal uniparental disomy (UPD; approximately
      30%). Most cases of AS result from the lack of a maternal contribution from this
      same region by maternal deletion (approximately 70%) or by paternal UPD
      (approximately 5%). Analysis of allelic methylation differences at the small
      nuclear ribonucleoprotein polypeptide N (SNRPN) locus can differentiate the
      maternally and paternally inherited chromosome 15 and can be used as a diagnostic
      test for AS and PWS. METHODS: Sodium bisulfite-treated genomic DNA was PCR
      amplified for the SNRPN gene. We used pyrosequencing to individually quantify the
      resulting artificial C/T sequence variation at CpG sites. Anonymized DNA samples
      from PWS patients (n = 40), AS patients (n = 31), and controls (n = 81) were
      analyzed in a blinded fashion with 2 PCR and 3 pyrosequencing reactions. We
      compared results from the pyrosequencing assays with those obtained with a
      commonly used methylation-specific PCR (MS-PCR) diagnostic protocol. RESULTS: The
      pyrosequencing assays had a sensitivity and specificity of 100% and provided
      quantification of methylation at 12 CpG sites within the SNRPN locus. The
      resulting diagnoses were 100% concordant with those obtained from the MS-PCR
      protocol. CONCLUSIONS: Pyrosequencing is a rapid and robust method for
      quantitative methylation analysis of the SNRPN locus and can be used as a
      diagnostic test for PWS and AS.

PMID- 16574762
TI  - Butyrylcholinesterase: association with the metabolic syndrome and identification
      of 2 gene loci affecting activity.
AB  - BACKGROUND: Plasma cholinesterase activity is known to be correlated with plasma
      triglycerides, HDL- and LDL-cholesterol, and other features of the metabolic
      syndrome. A role in triglyceride metabolism has been proposed. Genetic variants
      that decrease activity have been studied extensively, but the factors
      contributing to overall variation in the population are poorly understood. We
      studied plasma cholinesterase activity in a sample of 2200 adult twins to assess
      covariation with cardiovascular risk factors and components of the metabolic
      syndrome, to determine the degree of genetic effects on enzyme activity, and to
      search for quantitative trait loci affecting activity. METHODS AND RESULTS:
      Cholinesterase activity was lower in women than in men before the age of 50, but
      increased to activity values similar to those in males after that age. There were
      highly significant correlations with variables associated with the metabolic
      syndrome: plasma triglyceride, HDL- and LDL-cholesterol, apolipoprotein B and E,
      urate, and insulin concentrations; gamma-glutamyltransferase and aspartate and
      alanine aminotransferase activities; body mass index; and blood pressure. The
      heritability of plasma cholinesterase activity was 65%. Linkage analysis with
      data from the dizygotic twin pairs showed suggestive linkage on chromosome 3 at
      the location of the cholinesterase (BCHE) gene and also on chromosome 5.
      CONCLUSIONS: Our results confirm and extend the connection between
      cholinesterase, cardiovascular risk factors, and metabolic syndrome. They
      establish a substantial heritability for plasma cholinesterase activity that
      might be attributable to variation near the structural gene and at an independent
      locus.

PMID- 16574763
TI  - Assay for measurement of intact B-type natriuretic peptide prohormone in blood.
AB  - BACKGROUND: B-Type natriuretic peptide (BNP1-32) as well as the N-terminal
      fragment of the prohormone containing residues 1-76 (NT-proBNP1-76), both
      cleavage products of the precursor proBNP1-108, are reported to be powerful
      markers for prognosis and risk stratification of heart failure. However, the
      intact precursor also circulates in the bloodstream. Assays for the detection of
      these cleavage products have been developed, but most of these assays may
      overestimate the concentrations of the cleavage products because they also
      measure the precursor form. It is therefore important to develop an immunoassay
      that specifically measures solely proBNP1-108 in plasma. METHODS: After carefully
      designing the peptide used to immunize mice, we selected a specific monoclonal
      antibody (mAb Hinge76) that recognizes the cleavage site of proBNP1-108, an
      epitope present only in the precursor form. mAb Hinge76 recognizes recombinant
      proBNP1-108 in a dose-dependent manner, without any significant cross-reactivity
      with either recombinant NT-proBNP1-76 or synthetic BNP1-32. By combining mAb
      Hinge76 with a polyclonal antibody directed against BNP1-32, we were able to set
      up a proBNP1-108-specific sandwich immunoassay able to confirm the presence of
      proBNP1-108 in blood samples. RESULTS: From a cohort of 50 healthy persons and
      170 patients with congestive heart failure (CHF), our assay was able to
      differentiate healthy individuals from CHF patients (P <0.005). Interestingly,
      plasma proBNP1-108 concentrations were correlated with New York Heart Association
      classification. Moreover, a close relationship between proBNP1-108 and BNP1-32
      concentrations may exist, as a good correlation (r2= 0.89) was obtained when
      their respective concentrations were compared. CONCLUSION: mAb Hinge76 is the
      first proBNP1-108-specific mAb produced that allows accurate estimation of
      proBNP1-108 concentrations in plasma.

PMID- 16574764
TI  - Anti-transglutaminase antibody assay of the culture medium of intestinal biopsy
      specimens can improve the accuracy of celiac disease diagnosis.
AB  - BACKGROUND: We measured anti-transglutaminase (anti-tTG) antibody in the culture
      medium of intestinal biopsy specimens from patients with suspected celiac disease
      (CD) and evaluated the relationship between antibody production and severity of
      intestinal mucosal damage. METHODS: We performed diagnostic testing for CD on 273
      consecutive patients. In addition to routine histologic evaluation of duodenal
      biopsy specimens, we assayed anti-tTG antibodies in serum and in the culture
      medium of duodenal biopsy specimens. RESULTS: CD was diagnosed in 191 of the 273
      patients. Sensitivity and specificity of the serum anti-endomysium (EmA) and anti
      tTG assays were 83% and 85% and 99% and 95%, respectively, and both had 88%
      diagnostic accuracy. EmA and anti-tTG assayed in the culture medium had 98%
      sensitivity, 100% specificity, and 98% diagnostic accuracy (vs serum assays; P
      <0.0001). Twenty-nine CD patient specimens (16%) were negative for serum anti-tTG
      and EmA; for 24 of these patients, anti-tTG assay of the culture medium was
      positive. The CD patients whose biopsy specimens were positive for serum
      antibodies showed the following intestinal histologies: total villous atrophy,
      35%; severe villous atrophy, 25%; mild atrophy, 25%; villi with no atrophy but
      with increased intraepithelial lymphocytes, 15%. None of the CD patients whose
      specimens were negative for serum antibodies showed total or severe villous
      atrophy; 77% had mild villous atrophy, and 23% had no villous atrophy but had
      increased intraepithelial lymphocyte counts. Mild villous atrophy was also seen
      in specimens from approximately 15% of patients without CD. CONCLUSION: Anti-tTG
      assay of the culture medium of biopsy specimens can improve the accuracy of CD
      diagnosis in patients negative for serum antibodies.

PMID- 16574765
TI  - Thyroglobulin (Tg) recovery testing with quantitative Tg antibody measurement for
      determining interference in serum Tg assays in differentiated thyroid carcinoma.
AB  - BACKGROUND: Thyroglobulin (Tg) measurements are complicated by interference from
      Tg autoantibodies (TgAbs) or heterophilic antibodies (HAMAs). We used a new
      automated immunochemiluminometric assay (ICMA) with Tg recovery (TgR) on the
      Nichols Advantage platform to reassess the clinical utility of recovery testing
      in detecting interference in serum Tg measurement in patients with differentiated
      thyroid carcinoma. METHODS: We used 2 TgAb methods to detect Tg measurement
      interference with TgR and quantitative TgAb measurement in sera from 127
      patients. In a limited number of samples, we used an RIA as comparison method
      because it appeared to be minimally affected by TgAb. RESULTS: Prevalence of
      TgAbs was 13% (17 of 127) in either 1 or both TgAb assays. A compromised TgR
      (<70%) corresponded with TgAb positivity in either TgAb assay for 10 of 11
      samples (91%), whereas a normal TgR (> or =70%) corresponded with TgAb negativity
      in both assays for 95 of 101 samples (94%). In 6 TgAb-positive sera with TgR
      within the reference interval, there were no discrepancies between RIA and ICMA
      results. We obtained discordant RIA and ICMA results for 6 of 9 TgAb-positive
      sera with decreased TgR. In 1 TgAb-negative sample, the Tg result was falsely
      increased because of interference by HAMAs, as shown by an overrecovery of 126%.
      CONCLUSIONS: The Nichols Advantage TgR assay is a valuable complementary method
      to overcome the technical problem of interference by TgAbs or HAMAs in TgAb
      assays. Further studies are needed to confirm the potential added value of this
      TgR assay.

PMID- 16574766
TI  - Adenoviral-encoded antigens are presented efficiently by a subset of dendritic
      cells expressing high levels of alpha(v)beta3 integrins.
AB  - Dendritic cells (DC) play a central role in antigen presentation and are often
      targeted by adenoviral (Ad)-based gene therapy. However, DC lack the coxsackie-Ad
      receptor, and little is known about the process by which they acquire and present
      Ad-encoded antigens. We examined the expression of alpha(v)beta3 integrins
      (CD51/CD61) on mouse bone marrow-derived DC (BM-DC) and their susceptibility to
      transduction by Ad vectors. Less than 10% of BM-DC precursors expressed CD51, but
      expression increased over time in culture with granulocyte macrophage-colony
      stimulating factor (GM-CSF)/interleukin (IL)-4. After 7 days, 28 +/- 1.7% of
      CD11c+ DC expressed high levels of CD51 (CD51(hi)), and the remaining DC
      expressed low levels of CD51 (CD51(lo)). CD51(hi) CD express higher major
      histocompatibility complex type 1 (MHC I); however, both of the DC subsets
      expressed similar levels of MHC II and costimulatory molecules. When exposed to a
      first-generation Ad vector, transgene expression was restricted to the CD51(hi)
      DC subset and blocked by soluble peptides expressing an arginine, glycine,
      aspartic acid (RGD) sequence, confirming the role of integrins in viral entry.
      Consistent with this, a modified Ad expressing an RGD-binding sequence in its
      fiber knob (Ad-RGD) transduced the CD51(hi) DC subset with significantly higher
      efficiency. When BM-DC were transduced with an Ad-expressing ovalbumin (Ad-OVA),
      the CD51(hi) subset proved superior in activating OT-I (T cell receptor-OVA) T
      cells. Similar to in vitro effects, systemic administration of GM-CSF/IL-4
      increased the expression of CD51 on splenic DC and rendered these cells
      susceptible to Ad transduction. These results suggest that a limited subset of DC
      expressing high levels of alpha(v)beta3 integrins is preferentially transduced by
      Ad vectors and activates CD8+ T cell responses against Ad-encoded antigens.

PMID- 16574767
TI  - Naltrexone inhibits alcohol-mediated enhancement of HIV infection of T
      lymphocytes.
AB  - Acute and chronic alcohol abuse impairs various functions of the immune system
      and thus, has been implicated as a cofactor in the immunopathogenesis of human
      immunodeficiency virus (HIV) disease progression. We determined whether
      naltrexone, an opioid receptor antagonist widely used in the treatment of
      alcoholism, inhibits alcohol-mediated enhancement of HIV infection of T cells.
      Alcohol enhanced HIV infection of peripheral blood lymphocytes (PBL) and a human
      lymphoid cell line (CEMX174). Alcohol increased HIV X4 envelope (Env), not murine
      leukemia virus Env-pseudotyped infection of CEMX174 cells. Naltrexone antagonized
      the enhancing effect of alcohol on HIV infection of PBL and CEMX174 cells. The
      specific mu-opioid receptor antagonist, Cys2, Tyr3, Arg5, Pen7 (CTAP) amide, also
      blocked the enhancing effect of alcohol on HIV infection. Investigation of the
      underlying mechanism for the alcohol action showed that alcohol significantly
      increased endogenous beta-endorphin production and induced mu-opioid receptor
      mRNA expression in PBL and CEMX174 cells. The role of beta-endorphin in alcohol
      mediated enhancement of HIV infection was indicated by the observations that
      naltrexone and CTAP antagonized ether alcohol- or exogenous beta-endorphin
      mediated enhancement of HIV infection. These findings suggest a biological
      mechanism for the potential therapeutic benefit of naltrexone in treating HIV
      infected alcoholics.

PMID- 16574768
TI  - On the production of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2L) by
      human neutrophils.
AB  - Contrary to their traditional characterization as terminally differentiated
      effectors of inflammation, neutrophils are remarkably versatile cells. Indeed,
      their capacity to change phenotype under specific circumstances, their active
      involvement in the regulation and resolution of inflammation, their response to a
      wide variety of cytokines and chemotactic molecules, and their regulatory role in
      angiogenesis and tumor fate have made it clear that they represent far more than
      "short-lived cells devoid of transcriptional activities, that only release
      preformed mediators and kill pathogens". The multiple and amazing functional
      capacities of this cell type are also illustrated by the fact that the neutrophil
      may function as an important source of cytokines, at levels comparable with and
      in some cases, higher than those made by other leukocytes. To date, the families
      of cytokines, which in vitro or in vivo have been convincingly reported as being
      produced by neutrophils, include proinflammatory/anti-inflammatory cytokines,
      immunoregulatory cytokines, chemokines, angiogenic/fibrogenic factors, and tumor
      necrosis factor (TNF) superfamily members. The latter molecules are multifaceted
      cytokines whose integrated actions not only influence the development,
      homeostasis, and adaptive responses of many cells and tissue types but are also
      implicated in the antitumoral response. The recent findings that neutrophils
      produce in a finely regulated manner a TNF superfamily member involved in tumor
      cell killing and autoimmunity, namely TNF-related apoptosis-inducing ligand, open
      an additional perspective to exploit neutrophils for novel roles in anticancer
      responses and modulation of autoimmune diseases.

PMID- 16574769
TI  - CD8 T cells expressing killer Ig-like receptors and NKG2A are present in cord
      blood and express a more naive phenotype than their counterparts in adult blood.
AB  - We report that natural killer receptors (NKR) for major histocompatibility
      complex (MHC) class I molecules (MHC-NKR), the inhibitory killer immunoglobulin
      like receptors (KIR), and the CD94/NKG2A receptor are present on a small
      proportion of CD8 T cells in cord blood. On average, 1.67% of CD8 T cells in cord
      blood express KIR, and 0.74% expresses NKG2A, approximately fivefold less than in
      adult blood. CD8 T cells expressing MHC-NKR were present at similar levels in
      cord blood from preterm and term infants, and it is important that their presence
      was independent of placental pathology or infection. Cord blood CD8 T cells
      expressing MHC-NKR were relatively homogeneous and entirely CD27+, mostly CC
      chemokine receptor 7- and granzyme B-, with a majority being CD45RA+ and with no
      evidence for a skewed distribution of T cell receptor-Vbeta when tested in KIR+
      cells. This contrasted with adult blood, which was more heterogeneous, and where
      a majority of CD8 T cells expressing MHC-NKR was CD27- and granzyme B+.
      Functional studies revealed that cord blood KIR+ CD8 T cells were as capable as
      KIR- CD8 T cells in their ability to proliferate in response to CD3 ligation, yet
      it is interesting that they were more capable than KIR- CD8 T cells in their
      ability to secrete interferon-gamma. These data suggest that cord blood CD8 T
      cells expressing MHC-NKR are a unique subset of cells, distinct from those in
      adult blood, and may represent a less-differentiated population.

PMID- 16574770
TI  - Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of
      nuclear factor-kappaB (NF-kappaB), pyrrolidine dithiocarbamate.
AB  - Experimental autoimmune uveoretinitis (EAU) is a T helper type 1 cell-mediated
      autoimmune disease, which serves as a model of human chronic uveitis. In this
      model, cells of a monocyte/macrophage lineage and retinal antigen (Ag)-specific T
      cells infiltrate into the retina and cause inflammatory lesion, where
      proinflammatory cytokines and various stimuli activate a transcriptional factor,
      nuclear factor-kappaB (NF-kappaB), which modulates inflammation and enhances
      immune responses. In the present study, the therapeutic effect of administration
      of a NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), was examined in a
      murine EAU model. It was shown that PDTC ameliorated the clinical symptoms of EAU
      mice and significantly reduced the histopathological score compared with those in
      untreated mice. mRNA expressions of tumor necrosis factor alpha and interleukin
      1beta were suppressed in eyes of PDTC-treated EAU mice. However, when T cells
      from PDTC-treated EAU mice, Ag-presenting cells (APC), and the retinal Ag
      peptides were cocultured, these T cells showed the same level of proliferation as
      those from control mice. Furthermore, addition of PDTC in the culture of T cells
      from EAU mice, Ag, and APC completely abrogated the T cell-proliferative response
      and cytokine production. Pretreatment of Ag-primed T cells or APC with PDTC in
      vitro also reduced these responses. These results indicate that the inhibitory
      effect of PDTC is attributed mainly to the suppression of effector-phase
      responses including inflammation but not to the inhibition of T cell priming.
      Regulation of NF-kappaB pathway in the lesion could be a novel target for the
      successful control of uveoretinitis.

PMID- 16574771
TI  - Differential regulation by leukotrienes and calcium of Fc gamma receptor-induced
      phagocytosis and Syk activation in dendritic cells versus macrophages.
AB  - Macrophage (MO) phagocytosis via the Fc receptor for immunoglobulin G (Fc gammaR)
      requires the spleen tyrosine kinase (Syk) and serves an important antimicrobial
      function. We have reported previously that Fc gammaR-mediated ingestion and Syk
      activation in MO are amplified by and depend on the proinflammatory lipid
      mediator leukotriene B4 (LTB4). Although Fc gammaR-mediated ingestion is also
      important for antigen uptake, there is no information about LTB4 regulation of
      these processes in dendritic cells (DCs). In this study, we compared murine bone
      marrow (BM)-derived DCs to MO from BM, peritoneum, and the pulmonary alveolar
      space. Neither phagocytosis nor Syk activation in DCs was influenced by exogenous
      LTB4. Unlike the various MO populations, Syk activation in DCs was likewise
      unaffected by pharmacologic or genetic strategies to inhibit endogenous LTB4
      synthesis or to block the high-affinity LTB4 receptor BLT1. DCs were refractory
      to regulation by LTB4 despite the fact that they expressed BLT1 and mobilized
      intracellular calcium in response to its ligation. This resistance to LTB4 in DCs
      instead reflected the fact that in contrast to MO, Syk activation in DCs was
      itself entirely independent of calcium. These results identify a fundamental
      difference in Fc gammaR signaling between DCs and MO, which may relate to the
      divergent, functional consequences of target ingestion in the two cell types.

PMID- 16574772
TI  - Spatial dynamics of receptor-mediated endocytic trafficking in budding yeast
      revealed by using fluorescent alpha-factor derivatives.
AB  - Much progress defining the order and timing of endocytic internalization events
      has come as a result of real-time, live-cell fluorescence microscopy. Although
      the availability of numerous endocytic mutants makes yeast an especially valuable
      organism for functional analysis of endocytic dynamics, a serious limitation has
      been the lack of a fluorescent cargo for receptor-mediated endocytosis. We have
      now synthesized biologically active fluorescent mating-pheromone derivatives and
      demonstrated that receptor-mediated endocytosis in budding yeast occurs via the
      clathrin- and actin-mediated endocytosis pathway. We found that endocytic
      proteins first assemble into patches on the plasma membrane, and then alpha
      factor associates with the patches. Internalization occurs next, concomitant with
      actin assembly at patches. Additionally, endocytic vesicles move toward early
      endosomes on actin cables. Early endosomes also associate with actin cables, and
      they actively move toward endocytic sites to capture vesicles being released from
      the plasma membrane. Thus, endocytic vesicle formation and capture of the newly
      released vesicles by early endosomes occur in a highly concerted manner, mediated
      by the actin cytoskeleton.

PMID- 16574773
TI  - A noncoding RNA is a potential marker of cell fate during mammary gland
      development.
AB  - PINC is a large, alternatively spliced, developmentally regulated, noncoding RNA
      expressed in the regressed terminal ductal lobular unit-like structures of the
      parous mammary gland. Previous studies have shown that this population of cells
      possesses not only progenitor-like qualities (the ability to proliferate and
      repopulate a mammary gland) and the ability to survive developmentally programmed
      cell death but also the inhibition of carcinogen-induced proliferation. Here we
      report that PINC expression is temporally and spatially regulated in response to
      developmental stimuli in vivo and that PINC RNA is localized to distinct foci in
      either the nucleus or the cytoplasm in a cell-cycle-specific manner. Loss-of
      function experiments suggest that PINC performs dual roles in cell survival and
      regulation of cell-cycle progression, suggesting that PINC may contribute to the
      developmentally mediated changes previously observed in the terminal ductal
      lobular unit-like structures of the parous gland. This is one of the first
      reports describing the functional properties of a large, developmentally
      regulated, mammalian, noncoding RNA.

PMID- 16574774
TI  - A mechanism for diversity in warning signals: conspicuousness versus toxicity in
      poison frogs.
AB  - Many animals advertise their chemical defense to predators with conspicuous
      coloration and unpalatability, but little is known about the information in these
      signal elements. To effectively avoid predation, is it more advantageous to
      invest in increased conspicuousness or greater noxiousness, or to allocate
      equally to both signal modalities? Using natural variation among poison frog
      species measured with spectral reflectance and toxicity assays, we tested the
      relative importance of warning signal components with predator-learning and
      avoidance experiments. We demonstrate that closely related species use
      alternative strategies: increasing either conspicuousness or toxicity affords
      equivalent avoidance by predators and provides protection to nontoxic mimic
      species. These equally effective predator avoidance tactics demonstrate different
      aposematic solutions for two potentially costly signal components, providing a
      mechanism for natural diversity in warning signals.

PMID- 16574775
TI  - Turing instability mediated by voltage and calcium diffusion in paced cardiac
      cells.
AB  - In cardiac cells, the coupling between the voltage across the cell membrane
      (V(m)) and the release of calcium (Ca) from intracellular stores is a crucial
      ingredient of heart function. Under abnormal conditions and/or rapid pacing, both
      the action potential duration and the peak Ca concentration in the cell can
      exhibit well known period-doubling oscillations referred to as "alternans," which
      have been linked to sudden cardiac death. Fast diffusion of V(m) keeps action
      potential duration alternans spatially synchronized over the approximately 150
      mum-length scale of a cell, but slow diffusion of Ca ions allows Ca alternans
      within a cell to become spatially asynchronous, as observed in some experiments.
      This finding raises the question: When are Ca alternans spatially in-phase or out
      of-phase on subcellular length scales? This question is investigated by using a
      spatially distributed model of Ca cycling coupled to V(m). Our main finding is
      the existence of a Turing-type symmetry breaking instability mediated by V(m) and
      Ca diffusion that causes Ca alternans to become spontaneously out-of-phase at
      opposite ends of a cardiac cell. Pattern formation is governed by the interplay
      of short-range activation of Ca alternans, because of a dynamical instability of
      Ca cycling, and long-range inhibition of Ca alternans by V(m) alternans through
      Ca-sensitive membrane ionic currents. These results provide a striking example of
      a Turing instability in a biological context where the morphogens can be clearly
      identified, as well as a potential link between dynamical instability on
      subcellular scales and life-threatening cardiac disorders.

PMID- 16574776
TI  - Growth hormone is produced within the hippocampus where it responds to age, sex,
      and stress.
AB  - Recent studies by our group and others have demonstrated that growth hormone (GH)
      is produced endogenously within the hippocampal formation, a brain structure
      associated with learning and aspects of emotional experience. Here, we
      demonstrate that this endogenously produced GH is modulated by age and sex
      differences and the presence of estrogen. GH mRNA levels were higher in females
      than males, especially during proestrus, a stage of estrus when estrogen levels
      are elevated. Moreover, GH expression was increased in ovariectomized females
      that were treated with estradiol. This increase in GH mRNA in response to
      estrogen was followed by the appearance of GH protein and was negatively
      correlated with the expression levels of insulin-like growth factor-I mRNA,
      suggesting a feedback relationship between insulin-like growth factor-I and GH in
      the brain. GH mRNA levels were also elevated in primary neuronal cultures exposed
      to 17-beta-estradiol in vitro, further confirming the direct influence of
      estrogen on GH expression. Finally, exposure to an acute stressful event
      increased the expression and production of GH in both males and females. However,
      the stress-induced increase of GH in females depended on the stage of the estrous
      cycle in which they were exposed to the stressful event. Together, these data
      further demonstrate that GH is endogenously produced in the adult hippocampal
      formation, where it is regulated by age, estrogen, and exposure to environmental
      stimuli. These results suggest that GH may be involved in functions ascribed to
      the hippocampus, such as learning and the response to stressful experience.

PMID- 16574777
TI  - Mitochondrial thioredoxin-2 has a key role in determining tumor necrosis factor
      alpha-induced reactive oxygen species generation, NF-kappaB activation, and
      apoptosis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that is involved in
      numerous pathologies, in part through stimulation of the mitochondrial production
      of reactive oxygen species (ROS). Previous studies show that in addition to
      mitochondrial superoxide dismutase- and glutathione-dependent systems,
      mitochondria also contain thioredoxin-2 (Trx2), an antioxidant protein that can
      detoxify ROS. The purpose of this study was to determine whether Trx2 protects
      against oxidative damage triggered by TNF-alpha. After a 30-min treatment in HeLa
      cells, TNF-alpha (5-40 ng/ml) oxidized Trx2 but not cytoplasmic Trx1.
      Preferential, significant Trx2 oxidation occurred within 10 min of TNF-alpha
      treatment. Moreover, overexpression of Trx2, but not Trx1, decreased TNF-alpha
      induced ROS generation, suggesting mitochondrial compartmentation of ROS
      production and subsequent specific detoxification by Trx2, not Trx1.
      Overexpression of Trx2 or the active-site mutant C93S Trx2 was used to evaluate
      their downstream effects following TNF-alpha stimulation. Results showed that
      nuclear translocation of NF-kappaB was inhibited with Trx2 overexpression but not
      with the dominant negative active-site mutant C93S Trx2. Moreover, when
      cotransfected with a NF-kappaB-luciferase reporter and then treated with TNF
      alpha, NF-kappaB activity was significantly attenuated with Trx2 overexpression
      but not with C93S Trx2 expression. Trx2 overexpression, but not C93S Trx2,
      significantly inhibited TNF-alpha-induced apoptosis as measured by terminal dUTP
      nick-end labeling assay. These findings support the interpretation that
      mitochondrial-generated ROS is a principal component in TNF-alpha-induced effects
      and that Trx2 blocks TNF-alpha-induced ROS generation and downstream NF-kappaB
      activation and apoptosis.

PMID- 16574778
TI  - Examining the influence of the Journal of Pediatric Psychology: an empirical
      approach.
AB  - OBJECTIVE: To empirically examine whether research published in the Journal of
      Pediatric Psychology (JPP) guides research both within and outside the field of
      pediatric psychology. METHODS: Articles published in JPP from 2000 to 2004 were
      evaluated to determine the frequency with which articles in JPP from 2000
      influenced subsequent research. Citation rates by other journals were also
      examined. RESULTS: Articles in JPP from 2000 were frequently cited in subsequent
      research, but authors rarely cited previous research as being instrumental in the
      development of their study design. Articles in JPP from 2000 were also frequently
      cited by outside journals. Specifically, journals classified as "medical and
      medical subspecialties" had the highest rates of citing JPP articles.
      CONCLUSIONS: The finding that JPP is cited both within JPP and other journals
      provides further evidence that pediatric psychology is a thriving
      interdisciplinary field.

PMID- 16574779
TI  - Specific plasma membrane binding sites for polyphenols, including resveratrol, in
      the rat brain.
AB  - Using [3H]resveratrol (3,5,4'-trihydroxy-trans-stilbene) as radioligand, we
      investigated the possible existence of specific polyphenol binding sites at the
      level of the cellular plasma membrane in rat brain. Specific [3H]resveratrol
      binding sites were found to be enriched in the plasma membrane pellet with lower
      levels in the nuclear and cell debris fraction. Specific [3H]resveratrol binding
      to the plasma membrane fraction was sensitive to trypsin digestion and protein
      denaturation but not to DNase and RNase treatment. Saturation binding experiments
      revealed that specific [3H]resveratrol recognized a single class of sites with an
      apparent affinity (KD) of 220+/-45 nM and a maximal capacity (Bmax) of 1060+/-120
      fmol/mg protein. Various polyphenols and resveratrol derivatives competed against
      specific [3H]resveratrol binding in rat brain plasma membrane homogenates with
      the tea catechin gallates (epigallocatechin gallate and epicatechin gallate)
      displaying the highest affinities (Ki=25-45 nM) followed by resveratrol (Ki=102
      nM). Quantitative autoradiographic studies revealed that specific [3H]resveratrol
      binding sites are broadly distributed in the rat brain, with highest levels of
      labeling seen in the choroid plexus and subfornical organ. Finally, the potency
      of various polyphenols and resveratrol analogs in protecting hippocampal cells
      against beta-amyloid-induced toxicity correlated well (r=0.74) with their
      apparent affinity in the [3H]resveratrol binding assay. Taken together, these
      results suggest that the neuroprotective action of various polyphenols and
      resveratrol analogs could be mediated by the activation of common "receptor"
      binding sites particularly enriched at the level of the cellular plasma membrane
      in the rat brain.

PMID- 16574780
TI  - Chronic beta-adrenergic receptor stimulation induces cardiac apoptosis and
      aggravates myocardial ischemia/reperfusion injury by provoking inducible nitric
      oxide synthase-mediated nitrative stress.
AB  - The present study provides evidence that inducible nitric-oxide synthase (iNOS)
      mediated nitrative stress plays a pivotal role in chronic beta-adrenergic
      receptor (AR) stimulation-induced cardiac damage. In mice, 14 days of
      isoproterenol (ISO) stimulation via an osmotic minipump induced an up-regulation
      of iNOS as evidenced by increases in mRNA, protein expression, and immunochemical
      staining of myocardial iNOS. Serum level of C-reactive protein, an inflammatory
      mediator, was also markedly increased. Under chronic ISO stimulation, the up
      regulated iNOS produced a significantly increased amount of nitric oxide (NO) and
      its byproduct, peroxynitrite, in the circulation and heart and subsequently
      resulted in an accelerated myocardial apoptosis. Forty-minute myocardial ischemia
      (MI) and 24-h reperfusion (R) further increased NO production and peroxynitrite
      formation and resulted in an enlarged infarct size in mice receiving chronic ISO
      stimulation. However, the treatment with a selective iNOS inhibitor [N-(3
      (aminomethyl) benzyl)acetamidine] (1400W) or the use of a genetic modified animal
      (iNOS-knockout mice) markedly reduced iNOS-mediated production of NO and
      formation of peroxynitrite and consequently significantly decreased myocardial
      apoptosis and infarct size, showing a crucial link between iNOS-mediated
      nitrative stress and myocardial injury. In conclusion, chronic beta-AR
      stimulation up-regulates iNOS expression and increases NO production in the
      heart, which subsequently markedly enhances formation of reactive nitrogen
      species/peroxynitrite in the heart, thereby eliciting myocardial apoptosis and
      potentiating MI/R injury.

PMID- 16574781
TI  - Synthetic peroxisome proliferator-activated receptor-gamma agonists restore
      impaired vasorelaxation via ATP-sensitive K+ channels by high glucose.
AB  - The present study was designed to examine whether in the human artery, synthetic
      peroxisome proliferator-activated receptor (PPAR)-gamma agonists restore
      vasorelaxation as well as hyperpolarization via ATP-sensitive K+ channels
      impaired by the high concentration of D-glucose and whether the restoration may
      be mediated by the antioxidant capacity of these agents. The isometric force and
      membrane potential of human omental arteries without endothelium were recorded.
      The production rate of superoxide was evaluated using a superoxide-generating
      system with xanthine-xanthine oxidase in the absence of smooth muscle cells.
      Glibenclamide abolished vasorelaxation and hyperpolarization in response to
      levcromakalim. Addition of D-glucose (20 mM) but not L-glucose (20 mM) reduced
      this vasorelaxation and hyperpolarization. Synthetic PPAR-gamma agonists
      (troglitazone and rosiglitazone) and/or an inhibitor of superoxide generation
      (4,5-dihydroxy-1,3-benzene-disulfonic acid, Tiron), but not a PPAR-alpha agonist
      (fenofibrate), restored vasorelaxation and hyperpolarization in response to
      levcromakalim in arteries treated with D-glucose. Troglitazone and rosiglitazone,
      but not fenofibrate, decreased the production rate of superoxide without
      affecting uric acid generation. These findings suggest that synthetic PPAR-gamma
      agonists recover the function of ATP-sensitive K+ channels reduced by the high
      concentration of glucose in human vascular smooth muscle cells and that the
      effect of these agonists may be mediated in part by their antioxidant capacity.

PMID- 16574782
TI  - (5R)-5-hydroxytriptolide attenuated collagen-induced arthritis in DBA/1 mice via
      suppressing interferon-gamma production and its related signaling.
AB  - (5R)-5-Hydroxytriptolide (LLDT-8) displays strong immunosuppressive activities
      both in vitro and in vivo in our previous studies. This study aims to investigate
      whether LLDT-8 has antiarthritic potential in a murine model of type II bovine
      collagen (CII)-induced arthritis (CIA) and to show the mechanism(s) of LLDT-8
      action. DBA/1 mice were immunized with CII to induce arthritis and administered
      with LLDT-8. The severity of arthritis was evaluated according to the clinical
      score and joint damage. The effects of LLDT-8 on immune responses were determined
      by measurement of serum antibody levels, lymphocyte proliferation assay, cytokine
      assay, nitric oxide (NO) production, arginase activity assays, fluorescence
      activated cell sorting analysis of splenic Mac-1+ cells, as well as polymerase
      chain reaction analysis for interferon-gamma (IFN-gamma)-related gene expression.
      We showed that LLDT-8 treatment significantly reduced the incidence and severity
      of CIA. The preventive and therapeutic effects of LLDT-8 are associated with 1)
      reduction of serum anti-CII immunoglobulin (Ig) G, IgG2a, and IgG1 levels; 2)
      inhibition of CII-specific lymphocyte proliferation, IFN-gamma and interleukin-2
      production; 3) blockade of gene expressions in IFN-gamma signaling, including IFN
      gamma production pathways [signal transducer and activator of transcription
      (STAT) 1, T-box transcription factor, interleukin 12Rbeta2, and STAT4] and IFN
      gamma-induced chemokine transcription [macrophage inflammatory protein (Mip)
      1alpha, Mip-1beta, regulated on activation normally T cell expressed and
      secreted, and inducible protein 10]; and 4) retardation of the abnormal increase
      of NO via IFN-gamma/STAT1/interferon regulatory factor 1/inducible nitric-oxide
      synthase pathway and arginase activity. Moreover, the mRNA transcription of
      chemokine receptors was also suppressed [including C-C chemokine receptor (CCR)
      1, CCR5, and C-X-C chemokine receptor 3]. In conclusion, our data suggest that
      the antiarthritic effect of LLDT-8 is closely related to the blockade of IFN
      gamma signaling. LLDT-8 may have a therapeutic value in the treatment of
      rheumatoid arthritis.

PMID- 16574783
TI  - Conduct disorder and antisocial personality disorder in persons with severe
      psychiatric and substance use disorders.
AB  - Conduct disorder (CD) and antisocial personality disorder (ASPD) are established
      risk factors for substance use disorders in both the general population and among
      persons with schizophrenia and other severe mental illnesses. Among clients with
      substance use disorders in the general population, CD and ASPD are associated
      with more severe problems and criminal justice involvement, but little research
      has examined their correlates in clients with dual disorders. To address this
      question, we compared the demographic, substance abuse, clinical, homelessness,
      sexual risk, and criminal justice characteristics of 178 dual disorder clients
      living in 2 urban areas between 4 groups: No CD/ASPD, CD Only, Adult ASPD Only,
      and Full ASPD. Clients in the Adult ASPD Only group tended to have the most
      severe drug abuse severity, the most extensive homelessness, and the most
      lifetime sexual partners, followed by the Full ASPD group, compared with the
      other 2 groups. However, clients with Full ASPD had the most criminal justice
      involvement, especially with respect to violent charges and convictions. The
      results suggest that a late-onset ASPD subtype may develop in clients with severe
      mental illness secondary to substance abuse, but that much criminal behavior in
      clients with dual disorders may be due to the early onset of the full ASPD
      syndrome in this population and not the effects of substance use disorders.

PMID- 16574784
TI  - Vascular endothelial growth factor receptor-2 expression is induced by 17beta
      estradiol in ZR-75 breast cancer cells by estrogen receptor alpha/Sp proteins.
AB  - Vascular endothelial growth factor receptor-2 kinase insert domain receptor
      (VEGFR2/KDR) is critical for angiogenesis, and VEGFR2 mRNA and protein are
      expressed in ZR-75 breast cancer cells and induced by 17beta-estradiol (E2).
      Deletion analysis of the VEGFR2 promoter indicates that the proximal GC-rich
      region is required for both basal and hormone-induced transactivation, and
      mutation of one or both of the GC-rich motifs at -58 and -44 results in loss of
      transactivation. Electrophoretic mobility shift and chromatin immunoprecipitation
      assays show that Sp1, Sp3, and Sp4 proteins bind the GC-rich region of the VEGFR2
      promoter. Results of the chromatin immunoprecipitation assay also demonstrate
      that ERalpha is constitutively bound to the VEGFR2 promoter and that these
      interactions are not enhanced after treatment with E2, whereas ERalpha binding to
      the region of the pS2 promoter containing an estrogen-responsive element is
      enhanced by E2. RNA interference studies show that hormone-induced activation of
      the VEGFR2 promoter constructs requires Sp3 and Sp4 but not Sp1, demonstrating
      that hormonal activation of VEGFR2 involves a nonclassical mechanism in which
      ERalpha/Sp3 and ERalpha/Sp4 complexes activate GC-rich sites where Sp proteins
      but not ERalpha bind DNA. These results show for the first time that Sp3 and Sp4
      cooperatively interact with ERalpha to activate VEGFR2 and are in contrast to
      previous results showing that several hormone-responsive genes are activated by
      ERalpha/Sp1 in breast cancer cell lines.

PMID- 16574785
TI  - The thyroid hormone receptor-beta agonist GC-1 induces cell proliferation in rat
      liver and pancreas.
AB  - Thyroid hormones regulate cell growth, cell differentiation, and metabolic
      functions via interaction with the thyroid hormone nuclear receptors (TRs).
      Recently, a small class of halogen-free high-affinity thyroid hormone agonists
      has been developed that are highly selective for the TRbeta subtype. Because of
      the selective hyperthyroidism generated by one of these agonists, GC-1, this
      compound has the potential to be developed as a new therapeutic agent for the
      treatment of a variety of metabolic disturbances, including lipid disorders and
      obesity; thus, it becomes important to determine whether GC-1 has other unknown
      effects on potential target organs. The purpose of this study was to investigate
      the effect of GC-1 on cell proliferation in rat liver and pancreas. Rats treated
      with GC-1 (50 or 100 mug/100 g body weight) were killed at different time points.
      Hepatic and pancreatic cell proliferation was monitored by immunohistochemical
      determination of bromodeoxyuridine incorporation. The expression of cell cycle
      related genes was analyzed by Northern and Western analysis. The results show
      that GC-1 strongly stimulates rat hepatocyte proliferation in the absence of
      tissue injury. Although GC-1-induced hepatocyte proliferation was associated with
      a rapid increase in cyclin D1 mRNA levels, no change in the expression of c-jun
      and c-fos was observed. GC-1 also induced massive pancreatic cell proliferation.
      The results indicate that the TRbeta-selective agonist GC-1 is a strong mitogen
      for hepatocytes and pancreatic acinar cells. Furthermore, they suggest that the
      TRbeta receptor is the mediator for the mitogenic activity of thyroid hormone and
      other thyromimetics.

PMID- 16574786
TI  - Type 1 parathyroid hormone receptor (PTH1R) nuclear trafficking: association of
      PTH1R with importin alpha1 and beta.
AB  - Previous studies have shown that the type 1 PTH receptor (PTH1R), a class B G
      protein-coupled receptor, appears in the nucleus of target cells. Through
      immunofluorescence and deconvolution microscopy, we demonstrate that PTH1R,
      importin alpha(1), and importin beta are present within the nucleus and cytoplasm
      of osteoblast-like cell lines with the nuclear PTH1R being restricted to the
      nucleoplasm. Immunofluorescence studies showed that nuclear accumulation of PTH1R
      was associated with specific stages of the cell cycle. Using immunoprecipitation
      and affinity chromatography, we show that the PTH1R forms a complex with the
      importin family of transport molecules. Total cell protein from osteoblast-like
      cells was immunoprecipitated with antibodies for PTH1R, importin alpha(1), or
      importin beta. When the immunoprecipitates were separated and subsequently
      exposed to biotinylated PTH (1-84) a single band was present on the gel at 66.3
      kDa, corresponding to the PTH1R. To confirm the interaction between PTH1R and
      both importin alpha(1) and beta, the complex was purified from total cell protein
      of osteoblast-like cells using a PTH-linked affinity chromatography column. Using
      an anti-importin alpha(1) antibody, Western blots detected importin alpha(1) at
      58 kDa in the purified sample. Also, using an anti-importin beta antibody,
      Western blots detected importin beta at 94 kDa. These results indicate that the
      importins were associated with the PTH1R at the time of the purification. In
      conclusion, we show that the PTH1R forms a complex with the transport regulatory
      proteins, importin alpha(1) and importin beta, and that nuclear PTH1R is
      associated with the nucleoplasm.

PMID- 16574787
TI  - Fibroblast growth factor-2 is expressed by the bovine uterus and stimulates
      interferon-tau production in bovine trophectoderm.
AB  - Uterine-derived factors are essential for conceptus development and secretion of
      the maternal recognition-of-pregnancy factor, interferon-tau (IFNT), in ruminant
      species. The objectives of this study were to determine whether fibroblast growth
      factor-2 (FGF-2) is expressed in the bovine uterus during early pregnancy in
      cattle and to determine whether FGF-2 supplementation affects IFNT mRNA and
      protein abundance in bovine trophectoderm. FGF-2 mRNA was present in endometrium
      throughout the estrous cycle and was localized to the luminal and glandular
      endometrial epithelium at d 17-18 after estrus in pregnant and nonpregnant cows.
      Immunoreactive FGF-2 protein was detected within the endometrium and in the
      uterine lumen at d 17-18 after estrus, and concentrations did not differ based on
      pregnancy status. In a bovine trophectoderm cell line, CT-1, supplementation of
      medium with at least 1 ng/ml FGF-2 increased the incorporation of [(3)H]thymidine
      into DNA. Similarly, IFNT secretion from CT-1 cells increased after FGF-2
      supplementation (1-100 ng/ml) for 72 h. Abundance of IFNT mRNA in CT-1 cells
      increased after 24 h exposure to 1, 10, or 100 ng/ml FGF-2. In bovine
      blastocysts, FGF-2 supplementation did not affect cell number after 72 h of
      culture but did stimulate IFNT protein concentrations in conditioned medium. In
      summary, FGF-2 is present in the uterine lumen during early pregnancy and
      increases IFNT mRNA and protein abundance in trophectoderm. The magnitude by
      which FGF-2 stimulates IFNT expression suggests that this uterine-derived factor
      plays an active role in regulating the establishment and maintenance of pregnancy
      in ruminants.

PMID- 16574788
TI  - Angiotensin II inhibition reduces stress sensitivity of hypothalamo-pituitary
      adrenal axis in spontaneously hypertensive rats.
AB  - Angiotensin II type 1 (AT(1)) receptors are expressed within organs of the
      hypothalamo-pituitary-adrenal (HPA) axis and seem to be important for its stress
      responsiveness. Secretion of CRH, ACTH, and corticosterone (CORT) is increased by
      stimulation of AT(1) receptors. In the present study, we tested whether a
      blockade of the angiotensin II system attenuates the HPA axis reactivity in
      spontaneously hypertensive rats. Spontaneously hypertensive rats were treated
      with candesartan (2 mg/kg), ramipril (1 mg/kg), or mibefradil (12 mg/kg) for 5
      wk. In addition to baseline levels, CORT and ACTH responses to injection of CRH
      (100 microg/kg) were monitored over 4 h. mRNA of CRH, proopiomelanocortin,
      AT(1A), AT(1B), and AT(2) receptors was quantified by real-time PCR. All
      treatments induced equivalent reductions of blood pressure and had no effect on
      baseline levels of CORT and ACTH. However, both candesartan and ramipril
      significantly reduced CRH-stimulated plasma levels of ACTH (-26 and -15%) and
      CORT (-36 and -18%) and lowered hypothalamic CRH mRNA (-25 and -29%). Mibefradil
      did not affect any of these parameters. Gene expression of AT(1A), AT(1B), and
      AT(2) receptors within the HPA axis was not altered by any drug. We show for the
      first time that antihypertensive treatment by inhibition of AT(1) receptors or
      angiotensin-converting enzyme attenuates HPA axis reactivity independently of
      blood pressure reduction. This action is solely evident after CRH stimulation but
      not under baseline conditions. Both a reduced pituitary sensitivity to CRH and a
      down-regulation of hypothalamic CRH expression have the potential to reduce HPA
      axis activity during chronic AT(1) blockade or angiotensin-converting enzyme
      inhibition.

PMID- 16574789
TI  - Role of phosphatidylinositol 3-kinasegamma in the beta-cell: interactions with
      glucagon-like peptide-1.
AB  - Glucagon-like peptide-1 (GLP-1) increases beta-cell function and growth through
      protein kinase A- and phosphatidylinositol-3-kinase (PI3-K)/protein kinase B,
      respectively. GLP-1 acts via a G protein-coupled receptor, and PI3-Kgamma is
      known to be activated by G(betagamma.) Therefore, the role of PI3-Kgamma in the
      chronic effects of GLP-1 on the beta-cell was investigated using PI3-Kgamma
      knockout (KO) mice treated with the GLP-1 receptor agonist, exendin-4 (Ex4; 1
      nmol/kg sc every 24 h for 14 d). In vivo, glucose and insulin responses were
      similar in PBS- and Ex4-treated KO and wild-type (WT) mice. However, glucose
      stimulated insulin secretion was markedly impaired in islets from PBS-KO mice (P
      < 0.05), and this was partially normalized by chronic Ex4 treatment (P < 0.05).
      In contrast, insulin content was increased in PBS-KO islets, and this was
      paradoxically decreased by Ex4 treatment, compared with the stimulatory effect of
      Ex4 on WT islets (P < 0.05-0.01). Transfection of INS-1E beta-cells with small
      interfering RNA for PI3-Kgamma similarly decreased glucose-stimulated insulin
      secretion (P < 0.01) and increased insulin content. Basal values for beta-cell
      mass, islet number and proliferation, glucose transporter 2, glucokinase, and
      insulin receptor substrate-2 were increased in PBS-KO mice (P < 0.05-0.001) and,
      although they were increased by Ex4 treatment of WT animals (P < 0.05), they were
      decreased in Ex4-KO mice (P < 0.05-0.01). These findings indicate that PI3-Kgamma
      deficiency impairs insulin secretion, resulting in compensatory islet growth to
      maintain normoglycemia. Chronic Ex4 treatment normalizes the secretory defect,
      thereby relieving the pressure for expansion of beta-cell mass. These studies
      reveal a new role for PI3-Kgamma as a positive regulator of insulin secretion,
      and reinforce the importance of GLP-1 for the maintenance of normal beta-cell
      function.

PMID- 16574790
TI  - Molecular evolution of proadrenomedullin N-terminal 20 peptide (PAMP): evidence
      for gene co-option.
AB  - Posttranslational processing of proadrenomedullin generates two biologically
      active peptides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide
      (PAMP). Sequence comparison of homologous proadrenomedullin genes in vertebrate
      evolution shows a high degree of stability in the reading frame for AM, whereas
      PAMP sequence changes rapidly. Here we investigate the functional significance of
      PAMP phylogenetic variation studying two of PAMP's better characterized
      physiological activities, angiogenic potential and antimicrobial capability, with
      synthetic peptides carrying the predicted sequence for human, mouse, chicken, and
      fish PAMP. All tested peptides induced angiogenesis when compared with untreated
      controls, but chicken and fish PAMP, which lack terminal amidation, were
      apparently less angiogenic than their human and mouse homologs. Confirming the
      role of amidation in angiogenesis, Gly-extended and free acid variants of human
      PAMP produced responses similar to the natural nonamidated peptides. In contrast,
      antimicrobial activity was restricted to human PAMP, indicating that this
      function may have been acquired at a late time during the evolution of PAMP.
      Interestingly, free acid human PAMP retained antimicrobial activity whereas the
      Gly-extended form did not. This fact may reflect the need for maintaining a
      tightly defined structural conformation in the pore-forming mechanism proposed
      for these antimicrobial agents. The evolution of PAMP provides an example of an
      angiogenic peptide that developed antimicrobial capabilities without losing its
      original function.

PMID- 16574791
TI  - Activation of the hypothalamo-pituitary-adrenal axis by isolation and restraint
      stress during lactation in ewes: effect of the presence of the lamb and suckling.
AB  - We investigated the effect of the presence and absence of lambs and suckling by
      lambs to attenuate activation of the hypothalamo-pituitary-adrenal (HPA) axis to
      isolation and restraint stress in lactating sheep. In experiment 1, blood samples
      were collected every 10 min from nonlactating (n = 5) and lactating (n = 5) ewes
      for 4 h before and during stress. In experiment 2, ewes (n = 6) were allocated to
      1) nonlactating, 2) lactating with lambs absent, 3) lactating with lambs present
      but unable to suckle, and 4) lactating with lambs present and able to suckle.
      Blood samples were collected over 8 h with no stress (control day) and for 4 h
      before and 4 h during stress (stress day). In experiment 1, the mean (+/-SEM)
      cortisol concentrations increased significantly (P < 0.05) in nonlactating ewes
      during stress but did not change in lactating ewes. In experiment 2, cortisol did
      not vary on the control day or pretreatment of the stress day but increased (P <
      0.05) during stress in all groups except lactating ewes with lambs present and
      able to suckle. The greatest cortisol response occurred in nonlactating ewes
      followed by lactating ewes with lambs absent and lactating ewes with lambs
      present but unable to suckle. During stress, the ACTH concentrations increased (P
      < 0.05) in nonlactating ewes and lactating ewes with lambs absent but not in
      lactating ewes with lambs present. We conclude that the activity of the HPA axis
      during isolation and restraint is reduced in lactating ewes and that the presence
      of lambs increases this level of attenuation.

PMID- 16574792
TI  - Kinome analysis reveals nongenomic glucocorticoid receptor-dependent inhibition
      of insulin signaling.
AB  - Glucocorticoids (GCs) are powerful immunosuppressive agents that control genomic
      effects through GC receptor (GR)-dependent transcriptional changes. A common
      complication of GC therapy is insulin resistance, but the underlying molecular
      mechanism remains obscure. Evidence is increasing for rapid genomic-independent
      GC action on cellular physiology. Here, we generate a comprehensive description
      of nongenomic GC effects on insulin signaling using peptide arrays containing
      1,176 different kinase consensus substrates. Reduced kinase activities of the
      insulin receptor (INSR) and several downstream INSR signaling intermediates (i.e.
      p70S6k, AMP-activated protein kinase, glycogen synthase kinase-3, and Fyn) were
      detected in adipocytes and T lymphocytes due to short-term treatment with
      dexamethasone (DEX), a synthetic fluorinated GC. Western blot analysis confirmed
      suppressed phosphorylation of the INSR and a series of downstream INSR targets
      (i.e. INSR substrate-1, p70S6k, protein kinase B, phosphoinositide-dependent
      protein kinase, Fyn, and glycogen synthase kinase-3) after DEX treatment. DEX
      inhibited insulin signaling through a GR-dependent (RU486 sensitive) and
      transcription-independent (actinomycin D insensitive) mechanism. Overall, we
      postulate here a molecular mechanism for GC-induced insulin resistance based on
      nongenomic GR-dependent inhibition of insulin signaling.

PMID- 16574793
TI  - Seminal plasma promotes the expression of tumorigenic and angiogenic genes in
      cervical adenocarcinoma cells via the E-series prostanoid 4 receptor.
AB  - E-series prostanoid (EP)4 receptor is up-regulated in numerous cancers, including
      cervical carcinomas, and has been implicated in mediating the effects of
      prostaglandin (PG)E(2) in tumorigenesis. In addition to regulation by
      endogenously biosynthesized PGE(2), neoplastic cervical epithelial cells in
      sexually active women may also be regulated by PGs present in seminal plasma. In
      this study, we investigated the signal transduction pathways mediating the role
      of seminal plasma and PGE(2) in the regulation of tumorigenic and angiogenic
      genes via the EP4 receptor in cervical adenocarcinoma (HeLa) cells. HeLa cells
      were stably transfected with EP4 receptor in the sense orientation. Seminal
      plasma and PGE(2) signaling via the EP4 receptor induced the activation of
      cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) promoters,
      expression of COX-2 and VEGF mRNA and protein, and secretion of VEGF protein into
      the culture medium. Treatment of HeLa cells with seminal plasma or PGE(2) also
      rapidly induced the phosphorylation of ERK1/2 via the EP4 receptor. Preincubation
      of cells with a specific EP4 receptor antagonist (ONO-AE2-227) or chemical
      inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase or MAPK
      kinase or cotransfection of cells with dominant-negative mutant cDNA targeted
      against the EGFR, serine/threonine kinase Raf, or MAPK kinase abolished the EP4
      induced activation of COX-2, VEGF, and ERK1/2. Therefore, we have demonstrated
      that seminal plasma and PGE(2) can promote the expression of tumorigenic and
      angiogenic factors, in cervical adenocarcinoma cells via the EP4 receptor, EGFR,
      and ERK1/2 signaling pathways.

PMID- 16574794
TI  - Neuropeptide S stimulates the hypothalamo-pituitary-adrenal axis and inhibits
      food intake.
AB  - Neuropeptide S (NPS) is a recently discovered peptide shown to be involved in the
      modulation of arousal and fear responses. It has also been shown that lateral
      ventricle administration of NPS causes a significant decrease in food intake.
      Neuropeptides involved in the modulation of arousal have been shown to be
      involved in the regulation of the hypothalamo-pituitary adrenal (HPA) axis and
      food intake. In this study, we have examined the effect of
      intracerebroventricular (ICV) administration of NPS on behavior, regulation of
      the HPA axis, and food intake. ICV NPS significantly increased plasma ACTH and
      corticosterone 10 and 40 min after injection, respectively. A single ICV
      injection of NPS caused a significant increase in rearing activity as well as
      ambulatory movement for up to 45 min after injection. We then studied the effect
      of paraventricular nucleus (PVN) administration of NPS on the regulation of the
      HPA axis, behavior, and food intake. There was a significant increase in plasma
      ACTH and corticosterone after a single NPS PVN injection. Incubation of
      hypothalamic explants with increasing concentrations of NPS caused a significant
      increase in CRH and arginine vasopressin release. In addition, PVN administration
      of NPS dose-dependently inhibited food intake in the first hour after injection,
      although no effect on food intake was seen after this time. PVN administration of
      NPS caused a significant increase in rearing activity. These data demonstrate a
      novel role for NPS in the stimulation of the HPA axis.

PMID- 16574795
TI  - Reduced expression of focal adhesion kinase disrupts insulin action in skeletal
      muscle cells.
AB  - Integrins mediate interactions between cells and extracellular matrix proteins
      that modulate growth factor signaling. Focal adhesion kinase (FAK) is a key
      multifunctional integrin pathway protein. We recently reported that disruption of
      FAK impairs insulin-mediated glycogen synthesis in hepatocytes. To test the
      hypothesis that FAK regulates skeletal muscle insulin action, we reduced FAK
      expression in L6 myotubes using FAK antisense. In untransfected myotubes, insulin
      stimulated both FAK tyrosine phosphorylation and kinase activity. Cells treated
      with antisense FAK showed 78 and 53% reductions in FAK mRNA and FAK protein,
      respectively, whereas insulin receptor substrate 1/2 and paxillin abundance were
      unaffected. Insulin-stimulated U-(14)C-glucose incorporation into glycogen was
      abolished by FAK antisense, and 2-deoxy-glucose uptake and glucose transporter 4
      (GLUT4) translocation were both markedly attenuated. Antisense FAK did not alter
      GLUT1 or GLUT3 protein abundance. Immunofluorescence staining showed decreased
      FAK Tyr(397) phosphorylation and reduced actin stress fibers. Thus, in skeletal
      myotubes, FAK regulates the insulin-mediated cytoskeletal rearrangement essential
      for normal glucose transport and glycogen synthesis. Integrin signaling may play
      an important regulatory role in muscle insulin action.

PMID- 16574796
TI  - Honeybee odometry and scent guidance.
AB  - We report on a striking asymmetry in search behaviour observed in honeybees
      trained to forage alternately at one of two feeder sites in a narrow tunnel. Bees
      were trained by periodically switching the position of a sucrose reward between
      relatively short and long distances in the tunnel. Search behaviour was examined
      in the training tunnel itself and in a fresh tunnel devoid of scent cues
      deposited by bees during training. Bees tested in the fresh tunnel exhibited a
      bias towards the shorter site, while bees tested in the training tunnel searched
      closer to the longer site. In additional experiments, we manipulated the position
      of scent cues, relative to the training location, in the testing tunnel. Bees
      generally searched at the site to which they were trained rather than at the
      position of the scent. Our data argue strongly against the hypothesis that bees
      rely exclusively on deposited scent to accurately localise a food source in
      natural foraging environments. We instead conclude that odometry and scent
      guidance contribute to honeybee food search in a manner reflecting the
      significance and relative reliability of sensory information.

PMID- 16574797
TI  - Temporal pattern cues in vibrational risk assessment by embryos of the red-eyed
      treefrog, Agalychnis callidryas.
AB  - The embryos of red-eyed treefrogs, Agalychnis callidryas, use vibrations
      transmitted through their arboreal egg clutch to cue escape hatching behavior
      when attacked by egg-eating snakes. Hatching early increases the risk of
      predation in the water, so embryos should avoid it unless they are in danger. We
      exposed egg clutches to intermittent vibrations with different combinations of
      vibration duration and spacing to examine the role of simple temporal pattern
      cues in the escape hatching response. Stimuli were bursts of synthetic white
      noise from 0 to 100 Hz, including the range of frequencies with substantial
      energy in snake attacks, and had approximately rectangular amplitude envelopes.
      Embryos hatched in response to a small range of temporal patterns and not in
      response to many others, rather than hatching to most vibrations except for
      certain patterns perceived as safe. Neither cycle length nor duty cycle predicted
      hatching response, except at extreme values where no hatching occurred; the
      highest energy stimuli elicited little or no hatching. Both vibration duration
      and inter-vibration interval strongly affected the hatching response. The highest
      levels of hatching were to durations of 0.5 s combined with intervals of 1.5-2.5
      s, and hatching decreased gradually with increasing difference of either duration
      or interval from these most effective stimuli. Vibration duration and interval
      appear to function as two necessary elements of a composite cue, rather than as
      redundant cues. This increases response specificity and reduces the range of
      stimuli that elicit hatching, likely reducing the chance of hatching
      unnecessarily in a benign disturbance. Vibration-cued hatching in A. callidryas
      embryos offers an opportunity to experimentally assess the behavioral decision
      rules underlying an effective and costly anti-predator defense.

PMID- 16574798
TI  - Dual inhibition of the dactyl opener muscle in lobster.
AB  - The dactyl opener neuromuscular system of crayfish and lobster has long been a
      popular model system for studies of synaptic physiology and its modulation.
      Previous studies of its neural innervation in both species have reported that
      whereas the opener excitor axon (OE) and the specific opener inhibitor (OI)
      innervate the entire muscle, the common inhibitor (CI) is restricted to a small
      number of the most proximal muscle fibers and is the physiologically weaker of
      the two inhibitors. Here, we show in the lobster that, contrary to previous
      reports, CI innervates fibers along the entire extent of the dactyl opener muscle
      and thus shares the innervation targets of OE and OI. To characterize the
      physiological function of CI in the lobster dactyl opener system, we
      independently stimulated both OI and CI and compared their effects. The
      physiological impact of each inhibitor was similar: inhibitors elicit inhibitory
      junction potentials of similar sizes, both trigger muscle relaxations and both
      inhibit excitatory junction potentials and muscle contractions to a comparable
      extent. Thus, in the periphery, CI and OI appear to be equally powerful
      inhibitors with similar physiological roles, both in suppressing contractions
      triggered by the excitor OE and in directly relaxing muscle tension. In light of
      these observations, our understanding of the physiological roles of specific and
      common inhibitors in crustacean motor control requires reevaluation.

PMID- 16574799
TI  - Sweet problems: insect traits defining the limits to dietary sugar utilisation by
      the pea aphid, Acyrthosiphon pisum.
AB  - Plant phloem sap is an extreme diet for animals, partly because of its high and
      variable sugar content. The physiological and feeding traits of the pea aphid
      Acyrthosiphon pisum that define the upper and lower limits to the range of
      dietary sucrose concentrations utilised by this insect were determined
      principally using chemically defined diets containing 0.125-1.5 mol l(-1)
      sucrose. On the diets with 0.125 mol l(-1) and 1.5 mol l(-1) sucrose, the aphids
      died as larvae within 8 and 14 days of birth, respectively. On the other diets,
      60-96% of aphids developed to adulthood, and the 0.5 mol l(-1) and 0.75 mol l(-1)
      diets supported the highest fecundity. The diet with 0.125 mol l(-1) sucrose was
      ingested at 36% of the rate of the 0.25 mol l(-1) sucrose diet, but >90% of
      ingested sucrose-carbon was assimilated on both diets. This suggests that the
      lower limit is dictated by the aphid feeding response, specifically, a
      requirement for a minimal concentration of sucrose for sustained feeding. The
      haemolymph osmotic pressure of aphids on diets with 0.125-1.5 mol l(-1) sucrose
      was up to 68% higher than on 0.125-1.0 mol l(-1) sucrose diets, but diet
      consumption and sucrose-carbon assimilation was not reduced on the very high
      sucrose diets relative to 1.0 mol l(-1) sucrose. This suggests that failure of
      the osmoregulatory capacity of the insects on high sucrose diets may define the
      upper limit to the range of dietary sucrose utilised by the aphids. The mean
      haemolymph osmotic pressure of aphids on plants with phloem sap containing 0.37
      0.97 mol l(-1) sucrose was 1.61+/-0.063 MPa (mean +/- s.e.m.), not significantly
      different from that (1.47+/-0.059 MPa) on diets with 0.25-1.0 mol l(-1) sucrose.
      It is concluded that the osmoregulatory response of aphids to diets and plants
      are comparable, and, more generally, that the feeding and osmoregulatory
      capabilities of the aphids are compatible with the phloem sugar levels commonly
      encountered by aphids feeding on plants.

PMID- 16574800
TI  - Effects of temperature on maximum acceleration, deceleration and power output
      during vertical running in geckos.
AB  - We studied performance and kinematics of the diurnal gekkonid lizard Phelsuma
      dubia while running vertically on a smooth surface at different temperatures.
      Trials were conducted at 5 degrees C intervals from 15 degrees C to 35 degrees C.
      High-speed video recordings and digitization were used to obtain measures of
      instantaneous velocity, acceleration, deceleration and mass-specific power output
      and maximal values for each were taken as performance measures. Kinematic
      variables were also obtained from high-speed video recordings and included stride
      length and duration, step (stance phase) length and duration, and duty factor.
      Maximal instantaneous velocity, acceleration and deceleration increased by a
      factor of approximately 1.7 between 15 degrees C and 25 degrees C, and less so
      (approximately 1.2x) between 25 degrees C and 35 degrees C. Mass-specific power
      output was more temperature-sensitive, increasing 2.5x up to 25 degrees C and a
      further 1.4x above that temperature. Stride length increased 1.5x over the entire
      temperature interval studied, while stride duration decreased by a factor of 1.9,
      suggesting that velocity is modulated by changes in both stride length and
      duration in P. dubia. Duty factor was not significantly influenced by
      temperature. Stride length was the only kinematic measure to be influenced by
      stride number, with second steps from a standstill being longer than first steps.
      We discuss the significance of velocity and acceleration being affected in a
      similar manner by temperature, and that speed is modulated by both changes in
      stride length and duration.

PMID- 16574801
TI  - Kidnapping of chicks in emperor penguins: a hormonal by-product?
AB  - The function and causes of kidnapping juveniles are little understood because
      individuals sustain some breeding costs to rear an unrelated offspring. Here we
      focus on the proximal causes of this behaviour in emperor penguins (Aptenodytes
      forsteri), whose failed breeders often kidnap chicks. We experimentally tested
      the hypothesis that kidnapping behaviour was the result of high residual levels
      of prolactin (PRL), a hormone involved in parental behaviour. Penguins with
      artificially decreased PRL levels by bromocriptine administration kidnapped
      chicks less often than control penguins. Within the bromocriptine treated group,
      kidnapping behaviour was not totally suppressed and the probability of kidnapping
      a chick was positively correlated to PRL levels measured before treatment. During
      breeding, emperor penguins have to forage in remote ice-free areas. In these
      birds, PRL secretion is poorly influenced by chick stimuli and has probably
      evolved to maintain a willingness to return to the colony after a long absence at
      sea. Therefore, penguins that have lost their chick during a foraging trip still
      maintain high residual PRL levels and this, combined with colonial breeding,
      probably facilitates kidnapping. We suggest that kidnapping in non-cooperative
      systems may result from a hormonal byproduct of a reproductive adaptation to
      extreme conditions.

PMID- 16574802
TI  - Heterothermy of free-living Arabian sand gazelles (Gazella subgutturosa marica)
      in a desert environment.
AB  - To test whether free-living desert ungulates employ heterothermy to reduce water
      loss, we measured core body temperature (T(b)) of six free-living Arabian sand
      gazelles (Gazella subgutturosa marica), a small desert antelope (12-20 kg) that
      lives in the deserts of Saudi Arabia, where air temperature (T(a)) often exceeds
      40 degrees C. We found that the mean daily T(b) varied by 2.6+/-0.8 degrees C
      during summer (June-July) and 1.7+/-0.3 degrees C during winter (January
      February); over both seasons, mean T(b) was 39.5+/-0.2 degrees C. During the day,
      in summer, T(b) increased by more than 2 degrees C when T(a)>T(b) and declined at
      night when T(a)<T(b), suggesting that gazelles stored heat during day and
      dissipated it by non evaporative means during night. The minimum T(b) was lower
      in summer (38.2+/-0.5 degrees C) than in winter (38.6+/-0.3 degrees C) despite
      the fact that the gradient between T(b) and T(a) was larger and solar radiation
      was lower in winter. Correlation between daily variation of T(b) and mean,
      maximal T(a)s were significant in summer, but not in winter. To dissipate the
      amount of heat stored by gazelles would require an evaporative water loss of 33.5
      ml H(2)O day(-1) in summer and 23.2 ml H(2)O day(-1) in winter. We tested whether
      the amplitude of daily variation in T(b) was influenced by the level of water
      provided to six captive sand gazelles maintained under controlled conditions in
      summer. The daily amplitude of T(b) was increased by 1.4 degrees C when gazelles
      were denied drinking water but supplied with pre-formed water in food, and by 1.1
      degrees C when they were denied both water and food. Gazelles denied only
      drinking water increased the amplitude of variation in T(b), whereas when denied
      both food and water, they seemed to undergo a dehydration-hyperthermia, with
      increased mean and maximal T(b) values but no decrease of minimal T(b). Free
      ranging and captive gazelles surviving on pre-formed water in natural food used
      heterothermy during summer with no elevation of plasma osmolality, indicating
      that they were not in a state of dehydration. Our data on variation in T(b) of
      gazelles provide an example of a small desert ungulate employing heterothermy to
      reduce evaporative water loss that would otherwise be required to maintain
      normothermic T(b).

PMID- 16574803
TI  - Wind generated by an attacking bat: anemometric measurements and detection by the
      praying mantis cercal system.
AB  - The wind-sensitive cercal system, well-known for mediating terrestrial escape
      responses, may also mediate insect aerial bat-avoidance responses triggered by
      wind generated by the approaching bat. One crucial question is whether enough
      time exists between detection and capture for the insect to perform a successful
      evasive maneuver. A previous study estimated this time to be 16 ms, based on
      cockroach behavioral latencies and a prediction for the detection time derived
      from a simulated predator moving toward a simulated prey. However, the detection
      time may be underestimated since both the simulated predator and prey lacked
      certain characteristics present in the natural situation. In the present study,
      actual detection times are measured by recording from wind-sensitive interneurons
      of a tethered praying mantis that serves as the target for a flying, attacking
      bat. Furthermore, using hot-wire anemometry, we describe and quantify the wind
      generated by an attacking bat. Anemometer measurements revealed that the velocity
      of the bat-generated wind consistently peaks early with a high acceleration
      component (an important parameter for triggering wind-mediated terrestrial
      responses). The physiological recordings determined that the mantis cercal system
      detected an approaching bat 74 ms before contact, which would provide the insect
      with 36 ms to perform a maneuver before capture. This should be sufficient time
      for the mantis to respond. Although it probably would not have time for a full
      response that completely evades the bat, even a partial response might alter the
      mantid's trajectory enough to cause the bat to mishandle the insect, allowing it
      to escape.

PMID- 16574804
TI  - Odours detected by rhinophores mediate orientation to flow in the nudibranch
      mollusc, Tritonia diomedea.
AB  - Tritonia diomedea is a useful neuroethological model system that can contribute
      to our understanding of the neural control of navigation. Prior work on both
      sensory and locomotory systems is complemented by recent field experiments, which
      concluded that these animals primarily use a combination of odours and water flow
      as guidance cues. We corroborate these field results by showing similar
      navigation behaviours in a flow tank. Slugs crawled upstream towards both prey
      and conspecifics, and turned downstream after crawling into a section of the flow
      tank downstream of a predator. Controls without upstream odour sources crawled
      apparently randomly. We then tested whether these behaviours depend on odours
      detected by the rhinophores. Outflow from a header tank was used to generate
      prey, predator and unscented control odour plumes in the flow tank. Slugs with
      rhinophores crawled upstream towards a prey odour plume source, turned downstream
      in a predator odour plume, and showed no reaction to a control plume. Slugs
      without rhinophores behaved similarly to controls, regardless of odour plume
      type. Finally, we used extracellular recordings from the rhinophore nerve to
      demonstrate that isolated rhinophores are chemosensitive. Afferent activity
      increased significantly more after application of all three odour types than
      after unscented control applications. Responses were odour specific. We conclude
      that rhinophores mediate orientation to flow, and suggest that future work should
      focus on the integration of mechanosensation and chemosensation during navigation
      in T. diomedea.

PMID- 16574805
TI  - The postnatal development of neocortical neurons and glial cells in the Gottingen
      minipig and the domestic pig brain.
AB  - The first mathematically unbiased estimates of neocortical cell numbers are
      presented from the developing pig brain, including a full description of tissue
      processing and optimal sampling for application of the stereological optical
      fractionator method in this species. The postnatal development of neocortical
      neurons and glial cells from the experimental Gottingen minipig was compared with
      the postnatal development of neocortical neurons in the domestic pig. A
      significant postnatal development was observed in the Gottingen minipig brain for
      both neuronal (28%; P=0.01) and glial cells (87%; P<0.01). A corresponding
      postnatal development of neurons was not detected in the domestic pig brain. The
      reason for this strain difference is not known. The mean total number of
      neocortical neurons is 324 million in the adult Gottingen minipig compared with
      432 million in the domestic pig. The glial-to-neuron cell ratio is around 2.2 in
      the adult Gottingen minipig. Based on these results, the domestic pig seems to be
      a more suitable model for evaluating the effects of developmental insults on
      human brain growth and neuronal development than the Gottingen minipig.

PMID- 16574806
TI  - Changes in composition of spider orb web sticky droplets with starvation and web
      removal, and synthesis of sticky droplet compounds.
AB  - The sticky spiral of araneoid spider orb webs consists of silk fibers coated with
      adhesive droplets. The droplets contain a variety of low-molecular-mass compounds
      (LMM). Within a species, a fairly consistent ratio of LMM is often observed, but
      substantial variability can exist. To gain insight into factors influencing LMM
      composition, spiders of three araneid species were starved and LMM from their
      webs were analyzed for changes in composition. To determine if these changes were
      consistent with the spider's ability to synthesize the different organic LMM,
      synthetic capacities were estimated following the feeding of radiolabeled
      metabolites. Some changes in droplet composition were broadly consistent with
      differing synthetic capacities: molar percentages of less readily synthesized
      compounds (e.g. choline, isethionate, N-acetyltaurine) typically declined with
      starvation, at least during a portion of the imposed fast, while more readily
      synthesized compounds (e.g. GABamide, glycine) tended to increase. Most striking
      was the apparent partial substitution of N-acetylputrescine by the more readily
      synthesized GABamide in fasting Argiope trifasciata. However, departures from
      expected compositional shifts demonstrated that synthetic capacity alone does not
      adequately predict sticky droplet compositional shifts with starvation. Moreover,
      feeding controls exhibited some changes in composition similar to starving
      spiders. As the webs of both feeding and starving spiders were removed for
      chemical analysis and could not be recycled, the loss of LMM contained in these
      webs likely contributed to similarities between treatments. In addition, feeding
      spiders molted, oviposited and/or built heavier webs. The added metabolic demands
      of these activities may have contributed to changes in composition similar to
      those resulting from starvation.

PMID- 16574807
TI  - Ontogeny of osmoregulation in embryos of intertidal crabs (Hemigrapsus
      sexdentatus and H. crenulatus, Grapsidae, Brachyura): putative involvement of the
      embryonic dorsal organ.
AB  - This study examined whether the existence of hyperosmotic internal fluids in
      embryos of euryhaline crabs (Hemigrapsus sexdentatus and H. crenulatus) in dilute
      seawater reflects osmotic isolation due to impermeability of the egg envelope, as
      proposed for other decapods, or active osmoregulation. When ovigerous crabs with
      eggs at gastrula stage were transferred from 100% seawater (osmolality 1000 mmol
      kg(-1)) to 50% seawater, embryogenesis and hatching of zoea were completed
      normally, but were delayed. Hatching failed if the transfer to 50% seawater
      occurred before gastrulation, and embryogenesis was abnormal in 25% seawater. In
      100% seawater, embryos at all stages were internally hyperosmotic by 150-250 mmol
      kg(-1). On transfer to 50% seawater, osmolality initially decreased but remained
      200-350 mmol kg(-1) hyperosmotic to the medium for several weeks until hatching.
      High efflux rates of tritium-labelled water (t((1/2)) 16-75 min) and (22)Na
      (t(1/2) 109-374 min) from H. crenulatus embryos were inconsistent with the
      osmotic isolation hypothesis. It is concluded that post-gastrula embryos were
      actively hyper-osmoregulating. The diffusional water permeability of the embryos
      decreased during development while the sodium efflux rate increased 10-fold. Very
      rapidly exchanging pools of water and sodium (t(1/2) a few seconds to minutes)
      probably corresponded to peri-embryonic fluid and implied that the egg envelope
      was a negligible barrier to diffusion of water and salts. Higher Na(+)/K(+)
      ATPase activities in late embryos of H. crenulatus incubated in 50% seawater than
      in embryos incubated in full strength seawater were consistent with an
      acclimation response. An area of the embryonic surface located over the yolk in
      the region of the embryonic dorsal organ stained with AgNO(3). Staining appeared
      at gastrulation, persisted throughout development and was lost at hatching.
      Deposits of AgCl between the outer and inner membranes, identified by X-ray
      microanalysis, suggest that the dorsal organ was a site of chloride extrusion. A
      model for osmoregulation in post-gastrula embryos is proposed: osmotic uptake of
      water is balanced by excretion of water and salts via the dorsal organ and salt
      loss is balanced by active uptake over the general embryonic ectoderm.

PMID- 16574808
TI  - Passive mechanical properties of legs from running insects.
AB  - While the dynamics of running arthropods have been modeled as a spring-mass
      system, no such structures have been discovered that store and return energy
      during bouncing. The hindleg of the cockroach Blaberus discoidalis is a good
      candidate for a passive, vertical leg spring because its vertically oriented
      joint axes of rotation limit the possibility of active movements and
      contributions of muscle properties. We oscillated passive legs while measuring
      force to determine the leg's dynamic, mechanical properties. The relative
      dimensionless stiffness of an individual cockroach leg was equal to that
      estimated for a single leg of a biped or quadruped. Leg resilience ranged from 60
      to 75%, affording the possibility that the leg could function as a spring to
      store and return the mechanical energy required to lift and accelerate the center
      of mass. Because hysteresis was independent of oscillation frequency, we rejected
      the use of a Voigt model - a simple spring in parallel with a viscous damper. A
      hysteretic damping model fit the cockroach leg force-displacement data over a
      wide range of frequencies and displacement using just two parameters. Rather than
      simply acting as a spring to minimize energy, we hypothesize that legs must
      manage both energy storage and absorption for rapid running to be most effective.

PMID- 16574809
TI  - Median fin function in bluegill sunfish Lepomis macrochirus: streamwise vortex
      structure during steady swimming.
AB  - Fishes have an enormous diversity of body shapes and fin morphologies. From a
      hydrodynamic standpoint, the functional significance of this diversity is poorly
      understood, largely because the three-dimensional flow around swimming fish is
      almost completely unknown. Fully three-dimensional volumetric flow measurements
      are not currently feasible, but measurements in multiple transverse planes along
      the body can illuminate many of the important flow features. In this study, I
      analyze flow in the transverse plane at a range of positions around bluegill
      sunfish Lepomis macrochirus, from the trailing edges of the dorsal and anal fins
      to the near wake. Simultaneous particle image velocimetry and kinematic
      measurements were performed during swimming at 1.2 body lengths s(-1) to describe
      the streamwise vortex structure, to quantify the contributions of each fin to the
      vortex wake, and to assess the importance of three-dimensional flow effects in
      swimming. Sunfish produce streamwise vortices from at least eight distinct
      places, including both the dorsal and ventral margins of the soft dorsal and anal
      fins, and the tips and central notched region of the caudal fin. I propose a
      three-dimensional structure of the vortex wake in which these vortices from the
      caudal notch are elongated by the dorso-ventral cupping motion of the tail,
      producing a structure like a hairpin vortex in the caudal fin vortex ring.
      Vortices from the dorsal and anal fin persist into the wake, probably linking up
      with the caudal fin vortices. These dorsal and anal fin vortices do not differ
      significantly in circulation from the two caudal fin tip vortices. Because the
      circulations are equal and the length of the trailing edge of the caudal fin is
      approximately equal to the combined trailing edge length of the dorsal and anal
      fins, I argue that the two anterior median fins produce a total force that is
      comparable to that of the caudal fin. To provide additional detail on how
      different positions contribute to total force along the posterior body, the
      change in vortex circulation as flow passes down the body is also analyzed. The
      posterior half of the caudal fin and the dorsal and anal fins add vortex
      circulation to the flow, but circulation appears to decrease around the peduncle
      and anterior caudal fin. Kinematic measurements indicate that the tail is angled
      correctly to enhance thrust through this interaction. Finally, the degree to
      which the caudal fin acts like a idealized two-dimensional plate is examined:
      approximately 25% of the flow near the tail is accelerated up and down, rather
      than laterally, producing wasted momentum, a loss not present in ideal two
      dimensional theories.

PMID- 16574810
TI  - Forage fibre digestion, rates of feed passage and gut fill in juvenile and adult
      red kangaroos Macropus rufus Desmarest: why body size matters.
AB  - Using red kangaroos Macropus rufus Desmarest, a large (>20 kg) marsupial
      herbivore, we compared the digestive capabilities of juveniles with those of
      mature, non-lactating females on high-quality forage (chopped lucerne Medicago
      sativa hay) of 43+/-1% neutral-detergent fibre (NDF) and poorer quality, high
      fibre forage (chopped oaten Avena sativa hay) of 64+/-1% NDF. On chopped lucerne
      apparent dry matter (DM) digestibilities by young-at-foot (YAF) red kangaroos (an
      age that would normally be taking some milk from their mother), weaned juveniles
      and mature females were similar (55-59%). On chopped oaten hay apparent DM
      digestibility was lower in the YAF (35.9+/-2.3%) followed by weaned (43.4+/-2.8%)
      and mature females (44.6+/-1%). The digestion of NDF and its components (mainly
      cellulose and hemicellulose) was lowest among the YAF followed by weaned and then
      mature females. The YAF and weaned kangaroos could not sustain growth on the poor
      quality diet, and appeared to be at or near maximal gut fill on both forages; the
      values being 114-122 g DM for YAF and 151-159 g DM for weaned kangaroos. Mean
      retention times (MRT) of particle and solute markers were significantly longer
      for the YAF and weaned kangaroos on oaten hay than on lucerne hay, and DM intake
      (g d(-1)) was approximately 50% lower on the oaten hay. In contrast, solute and
      particle MRTs in the mature females were not significantly affected by diet; they
      maintained DM intakes by increasing DM gut fill from 264+/-24 g on chopped
      lucerne to 427+/-26 g DM on chopped oaten hay. Clearly, the mature female
      kangaroos did not maximise gut fill on the high-quality forage, presumably as a
      consequence of their proportionally lower energy requirements compared with still
      growing juveniles. Overall, we have provided the first mechanistic link between
      the physiological constraints faced by juvenile red kangaroos in relation to
      their drought-related mortalities, rainfall and forage quality.

PMID- 16574811
TI  - Source location encoding in the fish lateral line canal.
AB  - The position of a hydrodynamic dipole source, as encoded in a linear array of
      mechano-detecting neuromasts in the fish lateral line canal, was
      electrophysiologically investigated. Measured excitation patterns along the
      lateral line were compared to theoretical predictions and were found to be in
      good agreement. The results demonstrate that information on the position of a
      vibrating source from a fish is linearly coded in the spatial characteristics of
      the excitation pattern of pressure gradients distributed along the lateral line
      canal. Several algorithms are discussed that could potentially be used by a fish
      to decode lateral line excitation patterns, in order to localise a source and its
      axis of vibration. Specifically, a wavelet transform of a 1-D excitation pattern
      is shown to reconstruct a 2-D image of dipole sources located within a distance
      comparable to the body length of a fish and with a close range spatial accuracy
      twice the inter-neuromast distance.

PMID- 16574812
TI  - Sperm selection and competition in pigs may be mediated by the differential
      motility activation and suppression of sperm subpopulations within the oviduct.
AB  - When spermatozoa from two or more boars are mixed and females inseminated, the
      resulting litters are often skewed in favour of one male but there is currently
      no satisfactory physiological explanation for this effect. However, to reach the
      oocytes, the spermatozoa must enter the oviduct where they are exposed to factors
      that modulate their activity. They either become sequestered within the oviductal
      sperm reservoir or bypass the reservoir and proceed towards the oocytes. The
      oviduct may therefore hold the key to mammalian sperm selection, thereby
      explaining why laboratory tests of sperm function, performed on whole ejaculates,
      are unable to account for the boar-specific skewing effects. We have previously
      shown that boar sperm motility is highly stimulated by bicarbonate, a naturally
      abundant component of oviductal fluid. Using motility-based sperm subpopulation
      analysis, we show here that the relative sizes of bicarbonate-responsive and
      unresponsive sperm subpopulations vary between individual boars. Proteins derived
      from oviduct epithelial plasma membranes suppress the activation response and
      modify sperm movement trajectories in a subpopulation-specific and dose-dependent
      manner. The suppression response varies between boars and some spermatozoa remain
      unsuppressed in the presence of oviductal proteins. When boars are ranked
      according to their susceptibility to bicarbonate-induced stimulation, rankings
      differ depending upon the presence or absence of oviductal proteins. The
      suppression response is not caused by inhibition of bicarbonate uptake; on the
      contrary this is enhanced by oviductal proteins. We suggest that the boar
      specific and sperm subpopulation-specific interactions between sperm motility
      activation and suppression responses are likely to result in sperm selection
      before the spermatozoa meet the oocytes.

PMID- 16574813
TI  - Ganglioside GM3 modulates tumor suppressor PTEN-mediated cell cycle progression-
      transcriptional induction of p21(WAF1) and p27(kip1) by inhibition of PI-3K/AKT
      pathway.
AB  - The simple ganglioside GM3 has been shown to have anti-proliferative effects in
      several in vitro and in vivo cancer models. Although the exogenous ganglioside
      GM3 has an inhibitory effect on cancer cell proliferation, the exact mechanism by
      which it prevents cell proliferation remains unclear. Previous studies showed
      that MDM2 is an oncoprotein that controls tumorigenesis through both p53
      dependent and p53-independent mechanisms, and tumor suppressor phosphatase and
      tensin homolog deleted on chromosome 10 (PTEN), a dual-specificity phosphatase
      that antagonizes phosphatidylinositol 3-kinase (PI-3K)/AKT signaling, is capable
      of blocking MDM2 nuclear translocation and destabilizing the MDM2 protein.
      Results from our current study show that GM3 treatment dramatically increases
      cyclin-dependent kinase (CDK) inhibitor (CKI) p21(WAF1) expression through the
      accumulation of p53 protein by the PTEN-mediated inhibition of the PI-3K/AKT/MDM2
      survival signaling in HCT116 colon cancer cells. Moreover, the data herein
      clearly show that ganglioside GM3 induces p53-dependent transcriptional activity
      of p21(WAF1), as evidenced by the p21(WAF1) promoter-driven luciferase reporter
      plasmid (full-length p21(WAF1) promoter and a construct lacking the p53-binding
      sites). Additionally, ganglioside GM3 enhances expression of CKI p27(kip1)
      through the PTEN-mediated inhibition of the PI-3K/AKT signaling. Furthermore, the
      down-regulation of the cyclin E and CDK2 was clearly observed in GM3-treated
      HCT116 cells, but the down-regulation of cyclin D1 and CDK4 was not. On the
      contrary, suppression of PTEN levels by RNA interference restores the enhanced
      expression of p53-dependent p21(WAF1) and p53-independent p27(kip1) through
      inactivating the effect of PTEN on PI-3K/AKT signaling modulated by ganglioside
      GM3. These results suggest that ganglioside GM3-stimulated PTEN expression
      modulates cell cycle regulatory proteins, thus inhibiting cell growth. We
      conclude that ganglioside GM3 represents a modulator of cancer cell proliferation
      and may have potential for use in colorectal cancer therapy.

PMID- 16574814
TI  - Emotions and golf performance: An IZOF-based applied sport psychology case study.
AB  - A multiple case study investigation is reported in which emotions and performance
      were assessed within the probabilistic individual zone of optimal functioning
      (IZOF) model (Kamata, Tenenbaum,& Hanin, 2002) to develop idiosyncratic emotion
      performance profiles. These profiles were incorporated into a psychological
      skills training (PST) intervention, with a focus on three emotional dimensions,
      that is, arousal, pleasantness, and functionality, and several psychological
      strategies employed during practice and competition. Two female varsity golfers
      at a major Division I university in the Southeast participated in the case study
      during the Spring 2002 season. The PST intervention resulted in enhanced
      emotional self-regulation skills and improved golf performance. Directions for
      future research into the IZOF model and implications for practical application of
      the model are discussed.

PMID- 16574815
TI  - Two-year follow-up of bibliotherapy and individual cognitive therapy for
      depressed older adults.
AB  - This study examined the stability of treatment gains after receiving either
      cognitive bibliotherapy or individual cognitive psychotherapy for depression in
      older adults. A 2-year follow-up of 23 participants from Floyd, Scogin, McKendree
      Smith, Floyd, and Rokke (2004) was conducted by comparing pre-and posttreatment
      scores with follow-up scores on the Hamilton Rating Scale for Depression (HRSD)
      and the Geriatric Depression Scale (GDS). Results indicated that treatment gains
      from baseline to the 2-year follow-up period were maintained on the HRSD and GDS,
      and there was not a significant decline from posttreatment to follow-up. There
      were no significant differences between the treatments on the GDS or HRSD at the
      2-year follow-up; however, bibliotherapy participants had significantly more
      recurrences of depression during the follow-up period.

PMID- 16574816
TI  - The effects of celeration lines on visual data analysis.
AB  - Previous visual analysis research reported that the overall agreement between
      visual analysis and statistical analysis was poor. In response, some researchers
      suggested the use of celeration lines to improve the accuracy and reliability of
      visual analysis. However, subsequent research reported little or no improvement
      in accuracy with such lines. The present study presented 5 board-certified
      behavior analysts with a series of behavioral graphs. The participants were asked
      to answer questions similar to those posed in previous studies but were also
      asked to talk aloud as they viewed each graph. Results indicate that the
      participants made accurate decisions for only 72% of the graphs and that
      celeration lines did not improve overall accuracy. The verbal protocol analysis
      suggests that participants were as likely to attend to trend when celeration
      lines were absent as they were when they were present, with the most differences
      attributable to varying participant competencies and not graph (i.e., celeration
      line) characteristics.

PMID- 16574817
TI  - Retaining pathological gamblers in cognitive behavior therapy through
      motivational enhancement: A pilot study.
AB  - Treatment for pathological gambling is in its infancy. Several cognitive and
      behavioral interventions have shown promise, but high attrition and relapse rates
      suggest that gamblers requesting treatment are not uniformly committed to change.
      This article describes an exploratory study with 9 severe pathological gamblers-
      in their majority horse race bettors--who were recruited from a community
      treatment center. The gamblers were treated with a hybrid intervention consisting
      of motivational enhancement and cognitive behavior therapy. All gamblers were
      retained in treatment and during a 12-month follow-up period. This retention rate
      was significantly higher than that of a control group of gamblers who received
      treatment as usual in the same community setting. Of the gamblers who received
      the experimental treatment, 6 maintained total abstinence during the 12-month
      follow-up period, 2 were significantly improved, and 1 remained unimproved. In
      addition to changing their gambling behavior, many clients made successful
      lifestyle changes. The possible benefits of combining a motivational intervention
      with cognitive behavior therapy are discussed.

PMID- 16574818
TI  - Behavioral treatment of chronic belching due to aerophagia in a normal adult.
AB  - Aerophagia, or excessive air swallowing, is a potential cause of belching,
      flatulence, bloating, and abdominal pain and may contribute to a worsening of
      gastrointestinal (GI) disorders. A limited number of published reports of
      aerophagia treatment indicate that behavioral methods may be of benefit. A case
      report is presented describing the behavioral treatment of chronic belching due
      to aerophagia in an adult female. The collaborative application of single
      participant design research helped identify open-mouth, diaphragmatic breathing
      and minimized swallowing as an effective intervention. Belching frequency was
      reduced from an average rate of 18 per 5-min interval during the baseline period
      to 3 per 5-min period after treatment. Results were maintained at an 18-month
      follow-up. Recommendations for the use of a brief treatment protocol with adults
      referred for chronic belching or other GI complaints attributed to aerophagia are
      discussed.

PMID- 16574819
TI  - Use of the structured descriptive assessment with typically developing children.
AB  - To date, only a limited number of studies have focused on functional assessment
      with typically developing populations. The most commonly reported method of
      functional assessment with this population seems to be descriptive assessment;
      however, the methods used in the descriptive assessment often are unclear. This
      is unfortunate as researchers and practitioners often are left with little
      guidance as to how to conduct a functional assessment with typically developing
      children. The purpose of this study was to determine whether the structured
      descriptive assessment (SDA) might be used with typically developing children.
      Four children with problem behavior participated in the study, and hypotheses
      about functional relations were developed for all children. Furthermore,
      efficacious interventions were developed and implemented for 2 children based on
      the results of the SDA.

PMID- 16574820
TI  - Retinoid signaling determines germ cell fate in mice.
AB  - Germ cells in the mouse embryo can develop as oocytes or spermatogonia, depending
      on molecular cues that have not been identified. We found that retinoic acid,
      produced by mesonephroi of both sexes, causes germ cells in the ovary to enter
      meiosis and initiate oogenesis. Meiosis is retarded in the fetal testis by the
      action of the retinoid-degrading enzyme CYP26B1, ultimately leading to
      spermatogenesis. In testes of Cyp26b1-knockout mouse embryos, germ cells enter
      meiosis precociously, as if in a normal ovary. Thus, precise regulation of
      retinoid levels during fetal gonad development provides the molecular control
      mechanism that specifies germ cell fate.

PMID- 16574821
TI  - Spin coupling in engineered atomic structures.
AB  - We used a scanning tunneling microscope to probe the interactions between spins
      in individual atomic-scale magnetic structures. Linear chains of 1 to 10
      manganese atoms were assembled one atom at a time on a thin insulating layer, and
      the spin excitation spectra of these structures were measured with inelastic
      electron tunneling spectroscopy. We observed excitations of the coupled atomic
      spins that can change both the total spin and its orientation. Comparison with a
      model spin-interaction Hamiltonian yielded the collective spin configuration and
      the strength of the coupling between the atomic spins.

PMID- 16574822
TI  - Synchrony, waves, and spatial hierarchies in the spread of influenza.
AB  - Quantifying long-range dissemination of infectious diseases is a key issue in
      their dynamics and control. Here, we use influenza-related mortality data to
      analyze the between-state progression of interpandemic influenza in the United
      States over the past 30 years. Outbreaks show hierarchical spatial spread
      evidenced by higher pairwise synchrony between more populous states. Seasons with
      higher influenza mortality are associated with higher disease transmission and
      more rapid spread than are mild ones. The regional spread of infection correlates
      more closely with rates of movement of people to and from their workplaces
      (workflows) than with geographical distance. Workflows are described in turn by a
      gravity model, with a rapid decay of commuting up to around 100 km and a long
      tail of rare longer range flow. A simple epidemiological model, based on the
      gravity formulation, captures the observed increase of influenza spatial
      synchrony with transmissibility; high transmission allows influenza to spread
      rapidly beyond local spatial constraints.

PMID- 16574823
TI  - Producing ultrastrong magnetic fields in neutron star mergers.
AB  - We report an extremely rapid mechanism for magnetic field amplification during
      the merger of a binary neutron star system. This has implications for the
      production of the short class of gamma-ray bursts, which recent observations
      suggest may originate in such mergers. In detailed magnetohydrodynamic
      simulations of the merger process, the fields are amplified by Kelvin-Helmholtz
      instabilities beyond magnetar field strength and may therefore represent the
      strongest magnetic fields in the universe. The amplification occurs in the shear
      layer that forms between the neutron stars and on a time scale of only 1
      millisecond, that is, long before the remnant can collapse into a black hole.

PMID- 16574824
TI  - In search of biosecurity.

PMID- 16574825
TI  - Disaster relief. Too late, earth scans reveal the power of a killer landslide.

PMID- 16574826
TI  - U.S. higher education. Foreign grad students show renewed interest.

PMID- 16574827
TI  - Higher education. $200 million gift for ancient world institute triggers
      backlash.

PMID- 16574828
TI  - DNA testing. Genetic screen misses mutations in women at high risk of breast
      cancer.

PMID- 16574829
TI  - U.K. budget. Government aids science teaching, streamlines research funding.

PMID- 16574830
TI  - Professional societies. Physics Institute settles suit, takes steps to increase
      diversity.

PMID- 16574831
TI  - Italy. CNR reform moves ahead, but critics cry foul.

PMID- 16574832
TI  - Applied physics. Nanocolumns give YBCO wires a big boost.

PMID- 16574833
TI  - Stem cells. Versatile sperm cells may offer alternative to embryos.

PMID- 16574834
TI  - Neuroscience. The thick and thin of brainpower: developmental timing linked to
      IQ.

PMID- 16574835
TI  - Biomedical research. A cure for medicine's ailments?

PMID- 16574836
TI  - Biomedical patents. Broad patent faces narrow odds in court battle.

PMID- 16574837
TI  - Lunar and planetary science conference. New signs of ancient life in another
      Martian meteorite?

PMID- 16574838
TI  - Lunar and planetary science conference. Snapshots from the meeting.

PMID- 16574839
TI  - Lunar and planetary science conference. Tumbling icy moons.

PMID- 16574840
TI  - Lunar and planetary science conference. Roughed up and far from home.

PMID- 16574841
TI  - American Physical Society meeting. Semiconductor advance may help reclaim energy
      from 'lost' heat.

PMID- 16574842
TI  - American Physical Society meeting. In a jumble of grains, a good hard shake
      restores order.

PMID- 16574843
TI  - American Physical Society meeting. New trick with silicon film could herald a
      bright future for rolled-up nanotubes.

PMID- 16574849
TI  - Invasive plants.

PMID- 16574850
TI  - Save the lab in Montemar, Chile.

PMID- 16574851
TI  - Scrapie and the origin of the Chinese "itchy".

PMID- 16574852
TI  - Disease but no sheep.

PMID- 16574853
TI  - Diversity. Preparing minority scientists and engineers.

PMID- 16574854
TI  - Plant science. Beta-glucans--brewer's bane, dietician's delight.

PMID- 16574855
TI  - Geophysics. Dangerous tectonics, fragile buildings, and tough decisions.

PMID- 16574856
TI  - Immunology. An antibody paradox, resolved.

PMID- 16574857
TI  - Astronomy. A neutron star in F-sharp.

PMID- 16574858
TI  - Stem cells and their niches.
AB  - A constellation of intrinsic and extrinsic cellular mechanisms regulates the
      balance of self-renewal and differentiation in all stem cells. Stem cells, their
      progeny, and elements of their microenvironment make up an anatomical structure
      that coordinates normal homeostatic production of functional mature cells. Here
      we discuss the stem cell niche concept, highlight recent progress, and identify
      important unanswered questions. We focus on three mammalian stem cell systems
      where large numbers of mature cells must be continuously produced throughout
      adult life: intestinal epithelium, epidermal structures, and bone marrow.

PMID- 16574859
TI  - How fast was wild wheat domesticated?
AB  - Prehistoric cultivation of wild wheat in the Fertile Crescent led to the
      selection of mutants with indehiscent (nonshattering) ears, which evolved into
      modern domestic wheat. Previous estimates suggested that this transformation was
      rapid, but our analyses of archaeological plant remains demonstrate that
      indehiscent domesticates were slow to appear, emerging approximately 9500 years
      before the present, and that dehiscent (shattering) forms were still common in
      cultivated fields approximately 7500 years before the present. Slow domestication
      implies that after cultivation began, wild cereals may have remained unchanged
      for a long period, supporting claims that agriculture originated in the Near East
      approximately 10,500 years before the present.

PMID- 16574860
TI  - Cenozoic plant diversity in the neotropics.
AB  - Several mechanisms have been proposed to explain the high levels of plant
      diversity in the Neotropics today, but little is known about diversification
      patterns of Neotropical floras through geological time. Here, we present the
      longest time series compiled for palynological plant diversity of the Neotropics
      (15 stratigraphic sections, 1530 samples, 1411 morphospecies, and 287,736
      occurrences) from the Paleocene to the early Miocene (65 to 20 million years ago)
      in central Colombia and western Venezuela. The record shows a low-diversity
      Paleocene flora, a significantly more diverse early to middle Eocene flora
      exceeding Holocene levels, and a decline in diversity at the end of the Eocene
      and early Oligocene. A good correlation between diversity fluctuations and
      changes in global temperature was found, suggesting that tropical climate change
      may be directly driving the observed diversity pattern. Alternatively, the good
      correspondence may result from the control that climate exerts on the area
      available for tropical plants to grow.

PMID- 16574861
TI  - Deformation and slip along the Sunda megathrust in the great 2005 Nias-Simeulue
      earthquake.
AB  - Seismic rupture produced spectacular tectonic deformation above a 400-kilometer
      strip of the Sunda megathrust, offshore northern Sumatra, in March 2005.
      Measurements from coral microatolls and Global Positioning System stations reveal
      trench-parallel belts of uplift up to 3 meters high on the outer-arc islands
      above the rupture and a 1-meter-deep subsidence trough farther from the trench.
      Surface deformation reflects more than 11 meters of fault slip under the islands
      and a pronounced lessening of slip trenchward. A saddle in megathrust slip
      separates the northwestern edge of the 2005 rupture from the great 2004 Sumatra
      Andaman rupture. The southeastern edge abuts a predominantly aseismic section of
      the megathrust near the equator.

PMID- 16574862
TI  - A linear homocatenated compound containing six indium centers.
AB  - In contrast to carbon and its heavier congeners, group 13 elements are rarely
      observed to catenate into linear chains. Here, we find that treatment of
      indium(I) iodide with a protonated N-xylyl beta-diketiminate and a strong
      potassium base in tetrahydrofuran yields a hexa-indium chain. X-ray
      crystallography revealed one beta-diketiminate ligand bound to each indium center
      with no bridging ligands supporting the five indium-indium single bonds. The
      terminal indium centers were capped with iodine. Electronic spectroscopy and
      computations on a model compound offer preliminary support for sigma
      delocalization along the chain.

PMID- 16574863
TI  - Rotational coherence and a sudden breakdown in linear response seen in room
      temperature liquids.
AB  - Highly energized molecules normally are rapidly equilibrated by a solvent; this
      finding is central to the conventional (linear-response) view of how chemical
      reactions occur in solution. However, when a reaction initiated by 33-femtosecond
      deep ultraviolet laser pulses is used to eject highly rotationally excited
      diatomic molecules into alcohols and water, rotational coherence persists for
      many rotational periods despite the solvent. Molecular dynamics simulations trace
      this slow development of molecular-scale friction to a clearly identifiable
      molecular event: an abrupt liquid-structure change triggered by the rapid
      rotation. This example shows that molecular relaxation can sometimes switch from
      linear to nonlinear response.

PMID- 16574864
TI  - High-performance high-TC superconducting wires.
AB  - We demonstrated short segments of a superconducting wire that meets or exceeds
      performance requirements for many large-scale applications of high-temperature
      superconducting materials, especially those requiring a high supercurrent and/or
      a high engineering critical current density in applied magnetic fields. The
      performance requirements for these varied applications were met in 3-micrometer
      thick YBa2Cu3O(7-delta) films epitaxially grown via pulsed laser ablation on
      rolling assisted biaxially textured substrates. Enhancements of the critical
      current in self-field as well as excellent retention of this current in high
      applied magnetic fields were achieved in the thick films via incorporation of a
      periodic array of extended columnar defects, composed of self-aligned nanodots of
      nonsuperconducting material extending through the entire thickness of the film.
      These columnar defects are highly effective in pinning the superconducting
      vortices or flux lines, thereby resulting in the substantially enhanced
      performance of this wire.

PMID- 16574865
TI  - Significant warming of the Antarctic winter troposphere.
AB  - We report an undocumented major warming of the Antarctic winter troposphere that
      is larger than any previously identified regional tropospheric warming on Earth.
      This result has come to light through an analysis of recently digitized and
      rigorously quality controlled Antarctic radiosonde observations. The data show
      that regional midtropospheric temperatures have increased at a statistically
      significant rate of 0.5 degrees to 0.7 degrees Celsius per decade over the past
      30 years. Analysis of the time series of radiosonde temperatures indicates that
      the data are temporally homogeneous. The available data do not allow us to
      unambiguously assign a cause to the tropospheric warming at this stage.

PMID- 16574866
TI  - Kaposi's sarcoma-associated herpesvirus fusion-entry receptor: cystine
      transporter xCT.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) is the
      causative agent of Kaposi's sarcoma and other lymphoproliferative syndromes often
      associated with HIV/AIDS. Functional complementary DNA selection for a receptor
      mediating KSHV cell fusion identified xCT, the 12-transmembrane light chain of
      the human cystine/glutamate exchange transporter system x-c. Expression of
      recombinant xCT rendered otherwise not susceptible target cells permissive for
      both KSHV cell fusion and virion entry. Antibodies against xCT blocked KSHV
      fusion and entry with naturally permissive target cells. KSHV target cell
      permissiveness correlated closely with endogenous expression of xCT messenger RNA
      and protein in diverse human and nonhuman cell types.

PMID- 16574867
TI  - A critical role for the innate immune signaling molecule IRAK-4 in T cell
      activation.
AB  - IRAK-4 is a protein kinase that is pivotal in mediating signals for innate immune
      responses. Here, we report that IRAK-4 signaling is also essential for eliciting
      adaptive immune responses. Thus, in the absence of IRAK-4, in vivo T cell
      responses were significantly impaired. Upon T cell receptor stimulation, IRAK-4
      is recruited to T cell lipid rafts, where it induces downstream signals,
      including protein kinase C activation through the association with Zap70. This
      signaling pathway was found to be required for optimal activation of nuclear
      factor kappaB. Our findings suggest that T cells use this critical regulator of
      innate immunity for the development of acquired immunity, suggesting that IRAK-4
      may be involved in direct signal cross talk between the two systems.

PMID- 16574868
TI  - Cellulose synthase-like CslF genes mediate the synthesis of cell wall (1,3;1,4)
      beta-D-glucans.
AB  - A characteristic feature of grasses and commercially important cereals is the
      presence of (1,3;1,4)-beta-d-glucans in their cell walls. We have used
      comparative genomics to link a major quantitative trait locus for (1,3;1,4)-beta
      d-glucan content in barley grain to a cluster of cellulose synthase-like CslF
      genes in rice. After insertion of rice CslF genes into Arabidopsis, we detected
      (1,3;1,4)-beta-d-glucan in walls of transgenic plants using specific monoclonal
      antibodies and enzymatic analysis. Because wild-type Arabidopsis does not contain
      CslF genes or have (1,3;1,4)-beta-d-glucans in its walls, these experiments
      provide direct, gain-of-function evidence for the participation of rice CslF
      genes in (1,3;1,4)-beta-d-glucan biosynthesis.

PMID- 16574869
TI  - Nurses' views on their involvement in euthanasia: a qualitative study in Flanders
      (Belgium).
AB  - BACKGROUND: Although nurses worldwide are confronted with euthanasia requests
      from patients, the views of palliative care nurses on their involvement in
      euthanasia remain unclear. OBJECTIVES: In depth exploration of the views of
      palliative care nurses on their involvement in the entire care process
      surrounding euthanasia. DESIGN: A qualitative Grounded Theory strategy was used.
      SETTING AND PARTICIPANTS: In anticipation of new Belgian legislation on
      euthanasia, we conducted semistructured interviews with 12 nurses working in a
      palliative care setting in the province of Vlaams-Brabant (Belgium). RESULTS:
      Palliative care nurses believed unanimously that they have an important role in
      the process of caring for a patient who requests euthanasia, a role that is not
      limited to assisting the physician when he is administering life terminating
      drugs. Nurses' involvement starts when the patient requests euthanasia and ends
      with supporting the patient's relatives and healthcare colleagues after the
      potential life terminating act. Nurses stressed the importance of having an open
      mind and of using palliative techniques, also offering a contextual understanding
      of the patient's request in the decision making process. Concerning the actual
      act of performing euthanasia, palliative care nurses saw their role primarily as
      assisting the patient, the patient's family, and the physician by being present,
      even if they could not reconcile themselves with actually performing euthanasia.
      CONCLUSIONS: Based on their professional nursing expertise and unique
      relationship with the patient, nurses participating as full members of the
      interdisciplinary expert team are in a key position to provide valuable care to
      patients requesting euthanasia.

PMID- 16574870
TI  - Transfusion contracts for Jehovah's Witnesses receiving organ transplants:
      ethical necessity or coercive pact?

PMID- 16574871
TI  - The impact of regional culture on intensive care end of life decision making: an
      Israeli perspective from the ETHICUS study.
AB  - BACKGROUND: Decisions of patients, families, and health care providers about
      medical care at the end of life depend on many factors, including the societal
      culture. A pan-European study was conducted to determine the frequency and types
      of end of life practices in European intensive care units (ICUs), including those
      in Israel. Several results of the Israeli subsample were different to those of
      the overall sample. OBJECTIVE: The objective of this article was to explore these
      differences and provide a possible explanation based on the impact of culture on
      end of life decision making. METHOD: All adult patients admitted consecutively to
      three Israeli ICUs (n = 2778) who died or underwent any limitation of life saving
      interventions between 1 January 1999 and 30 June 2000 were studied prospectively
      (n = 363). These patients were compared with a similar sample taken from the
      larger study (ethics in European intensive care units: ETHICUS) carried out in 37
      European ICUs. Patients were followed until discharge, death, or 2 months from
      the decision to limit therapy. End of life decisions were prospectively organised
      into one of five mutually exclusive categories: cardiopulmonary resuscitation
      (CPR), brain death, withholding treatment, withdrawing treatment, and active
      shortening of the dying process (SDP). The data also included patient
      characteristics (gender, age, ICU admission diagnosis, chronic disorders, date of
      hospital admission, date and time of decision to limit therapy, date of hospital
      discharge, date and time of death in hospital), specific therapies limited, and
      the method of SDP. RESULTS: The majority of patients (n = 252, 69%) had treatment
      withheld, none underwent SDP, 62 received CPR (17%), 31 had brain death (9%), and
      18 underwent withdrawal of treatment (5%). The primary reason given for limiting
      treatment was that the patient was unresponsive to therapy (n = 187). End of life
      discussions were held with 132 families (36%), the vast majority of which
      revolved around withholding treatment (91% of the discussions) and the remainder
      concerned withdrawing treatment (n = 11, 9%). There was a statistically
      significant association (chi2 = 830.93, df = 12, p < 0.0001) between the type of
      end of life decision and region-that is, the northern region of Europe, the
      central region, the southern region, and Israel. CONCLUSIONS: Regional culture
      plays an important part in end of life decision making. Differences relating to
      end of life decision making exist between regions and these differences can often
      be attributed to cultural factors. Such cultures not only affect patients and
      their families but also the health care workers who make and carry out such
      decisions.

PMID- 16574872
TI  - In defence of moral imperialism: four equal and universal prima facie principles.
AB  - Raanan Gillon is a noted defender of the four principles approach to healthcare
      ethics. His general position has always been that these principles are to be
      considered to be both universal and prima facie in nature. In recent work,
      however, he has made two claims that seem to present difficulties for this view.
      His first claim is that one of these four principles, respect for autonomy, has a
      special position in relation to the others: he holds that it is first among
      equals. We argue that this claim makes little sense if the principles are to
      retain their prima facie nature. His second claim is that cultural variation can
      play an independent normative role in the construction of our moral judgments.
      This, he argues, enables us to occupy a middle ground between what he sees as the
      twin pitfalls of moral relativism and (what he calls) moral imperialism. We argue
      that there is no such middle ground, and while Gillon ultimately seems committed
      to relativism, it is some form of moral imperialism (in the form of moral
      objectivism) that will provide the only satisfactory construal of the four
      principles as prima facie universal moral principles.

PMID- 16574873
TI  - Xenotransplantation: a bioethical evaluation.
AB  - Allograft shortage is a formidable obstacle in organ transplantation.
      Xenotransplantation, the interspecies transplantation of cells, tissues, and
      organs, or ex vivo interspecies exchange between cells, tissues, and organs is a
      frequently suggested alternative to this allograft shortage. As
      xenotransplantation steadily improves into a viable allotransplantation
      alternative, several bioethical considerations coalesce. Such considerations
      include the Helsinki declaration's guarantee of patients' rights to privacy;
      political red tape that may select for undermined socioeconomic groups as the
      first recipients of xenografts; industry incentives in xenotransplantation
      investments; conflicts of interest when a clinician supervises a patient as a
      research subject; the psychosocial impact of transplantation on the xenograft
      recipient, and the rights of animals. This review illuminates these issues
      through a conglomeration of expert opinion and relevant experimental studies.

PMID- 16574874
TI  - Bodily rights and property rights.
AB  - Whereas previous discussions on ownership of biological material have been much
      informed by the natural rights tradition, insufficient attention has been paid to
      the strand in liberal political theory represented by Felix Cohen, Tony Honore,
      and others, which treats property relations as socially constructed bundles of
      rights. In accordance with that tradition, we propose that the primary normative
      issue is what combination of rights a person should have to a particular item of
      biological material. Whether that bundle qualifies to be called "property" or
      "ownership" is a secondary, terminological issue. We suggest five principles of
      bodily rights and show how they can be applied to the construction of ethically
      appropriate bundles of rights to biological material.

PMID- 16574875
TI  - To know the value of everything--a critical commentary on B Bjorkman and S O
      Hansson's "Bodily rights and property rights".

PMID- 16574876
TI  - Euthanasia, efficiency, and the historical distinction between killing a patient
      and allowing a patient to die.

PMID- 16574877
TI  - Framing euthanasia.

PMID- 16574878
TI  - Assent in paediatric research: theoretical and practical considerations.
AB  - Guidelines around the world require children to provide assent for their
      participation in most research studies. Yet, little further guidance is provided
      on how review committees should implement this requirement, including which
      children are capable of providing assent and when the requirement for assent may
      be waived on the grounds that the research offers participating children the
      potential for important clinical benefit. The present paper argues that the
      assent requirement is supported by the importance of allowing children who are
      capable to make their own decisions. This suggests children are capable of assent
      when they become able to understand the research in question. While development
      varies across individual children, existing data suggest most children develop
      this ability by approximately age 14. Until instruments are developed to assess
      the assent capacity of individual children, this age should be used as the
      threshold for assent. In addition, the importance of protecting children from
      harm suggests that the sustained dissent of all children, including those who are
      unable to provide assent, should be respected. While the assent requirement may
      be waived when research participation offers the potential for important medical
      benefit that is unavailable outside the research context, analysis suggests that
      children's sustained dissent should be respected in all cases.

PMID- 16574879
TI  - A natural stem cell therapy? How novel findings and biotechnology clarify the
      ethics of stem cell research.
AB  - The natural replacement of damaged cells by stem cells occurs actively and often
      in adult tissues, especially rapidly dividing cells such as blood cells. An
      exciting case in Boston, however, posits a kind of natural stem cell therapy
      provided to a mother by her fetus-long after the fetus is born. Because there is
      a profound lack of medical intervention, this therapy seems natural enough and is
      unlikely to be morally suspect. Nevertheless, we feel morally uncertain when we
      consider giving this type of therapy to patients who would not naturally receive
      it. Much has been written about the ethics of stem cell research and therapy;
      this paper will focus on how recent advances in biotechnology and biological
      understandings of development narrow the debate. Here, the author briefly reviews
      current stem cell research practices, revisits the natural stem cell therapy case
      for moral evaluation, and ultimately demonstrates the importance of permissible
      stem cell research and therapy, even absent an agreement about the definition of
      when embryonic life begins. Although one promising technology, blighted ovum
      utilisation, uses fertilised but developmentally bankrupt eggs, it is argued that
      utilisation of unfertilised eggs to derive totipotent stem cells obviates the
      moral debate over when life begins. There are two existing technologies that
      fulfil this criterion: somatic cell nuclear transfer and parthenogenic stem cell
      derivation. Although these technologies are far from therapeutic, concerns over
      the morality of embryonic stem cell derivation should not hinder their
      advancement.

PMID- 16574880
TI  - Empirical research in bioethical journals. A quantitative analysis.
AB  - OBJECTIVES: The objective of this research is to analyse the evolution and nature
      of published empirical research in the fields of medical ethics and bioethics.
      DESIGN: Retrospective quantitative study of nine peer reviewed journals in the
      field of bioethics and medical ethics (Bioethics, Cambridge Quarterly of
      Healthcare Ethics, Hastings Center Report, Journal of Clinical Ethics, Journal of
      Medical Ethics, Kennedy Institute of Ethics Journal, Nursing Ethics, Christian
      Bioethics, and Theoretical Medicine and Bioethics). RESULTS: In total, 4029
      articles published between 1990 and 2003 were retrieved from the journals
      studied. Over this period, 435 (10.8%) studies used an empirical design. The
      highest percentage of empirical research articles appeared in Nursing Ethics (n =
      145, 39.5%), followed by the Journal of Medical Ethics (n = 128, 16.8%) and the
      Journal of Clinical Ethics (n = 93, 15.4%). These three journals account for
      84.1% of all empirical research in bioethics published in this period. The
      results of the chi2 test for two independent samples for the entire dataset
      indicate that the period 1997-2003 presented a higher number of empirical studies
      (n = 309) than did the period 1990-1996 (n = 126). This increase is statistically
      significant (chi2 = 49.0264, p < .0001). Most empirical studies employed a
      quantitative paradigm (64.6%, n = 281). The main topic of research was
      prolongation of life and euthanasia (n = 68). CONCLUSIONS: We conclude that the
      proportion of empirical research in the nine journals increased steadily from
      5.4% in 1990 to 15.4% in 2003. It is likely that the importance of empirical
      methods in medical ethics and bioethics will continue to increase.

PMID- 16574882
TI  - Effect of sex on perception of rectosigmoid stimuli in irritable bowel syndrome.
AB  - In irritable bowel syndrome (IBS) patients, the relationship between sex and
      sensitivity to visceral stimuli is incompletely understood. Our aim was to
      evaluate the effect of sex on perceptual responses to visceral stimulation in
      IBS. Fifty-eight IBS patients (mean age 42+/-1 yr; 34 men, 24 women) and 26
      healthy controls (mean age 38+/-3 yr; 9 men, 17 women) underwent barostat
      assisted distensions of the rectum and sigmoid colon. Rectal discomfort
      thresholds were measured using a randomized, phasic distension paradigm before
      and after repeated noxious sigmoid stimulation (SIG, 60-mmHg pulses). Sex had a
      significant effect on rectal discomfort thresholds. Women with IBS were the most
      sensitive (lower thresholds [27+/-2.7 mmHg] and higher ratings), with
      significantly lower rectal discomfort thresholds compared with men with IBS (38+/
      2.3 mmHg) and healthy women who were the least sensitive (41.9+/-3.2 mmHg; both
      P<0.01). There were no significant differences in rectal discomfort thresholds
      between healthy men (34+/-4.3 mmHg) and men with IBS. Across both IBS and control
      groups, women demonstrated a significant lowering of discomfort thresholds after
      noxious sigmoid stimulation (P<0.01), while men did not. Sex significantly
      influences perceptual sensitivity to rectosigmoid distension. Women show greater
      perceptual responses to this paradigm.

PMID- 16574884
TI  - Leptin inhibits swallowing in rats.
AB  - Swallowing is under the control of premotoneurons located in the medullary
      solitary tract nucleus. Although rats with transected midbrain do not seek out
      food, they are able to ingest food present near the mouth, and acute food
      deprivation induces an increase in food intake. Leptin is a satiety signal that
      regulates feeding behavior. Because leptin receptors are found within the caudal
      brainstem, and because food intake is regulated in midbrain transected rats, this
      study tested the hypothesis that leptin is able to modify the activity of
      premotoneurons involved in swallowing. Leptin was microinjected at the
      subpostremal level of the medullary solitary tract nucleus in anesthetized Wistar
      rats. Electromyographic electrodes in sublingual muscles allowed recording of
      swallowing induced by stimulation of sensitive fibers of the superior laryngeal
      nerve. Repeated stimulation induced rhythmic swallowing. Microinjection of leptin
      (0.1 pg and 0.1 ng) in the swallowing center induced an inhibition of rhythmic
      swallowing (latency of <30 s) as shown by the reduced number and strength of
      electromyographic activities, which could last several minutes. The threshold of
      the leptin-induced inhibition was close to 0.1 pg. Interestingly, the inhibitory
      effect of leptin was not observed in leptin receptor-deficient Zucker rats. Here
      we show that, in Wistar rats, leptin already known to modulate the discharge of
      medullary solitary tract nucleus-sensitive neurons involved in satiety reflexes
      can also modify the activity of swallowing premotoneurons, thereby inhibiting an
      essential motor component of feeding behavior.

PMID- 16574886
TI  - Activation of lateral parabrachial nucleus neurons restores blood pressure and
      sympathetic vasomotor drive after hypotensive hemorrhage.
AB  - Lesions of the lateral parabrachial nucleus (LPBN) impair blood pressure recovery
      after hypotensive blood loss (Am J Physiol Regul Integr Comp Physiol 280: R1141,
      2001). This study tested the hypothesis that posthemorrhage blood pressure
      recovery is mediated by activation of neurons, located in the ventrolateral
      aspect of the LPBN (VL-LPBN), that initiates blood pressure recovery by restoring
      sympathetic vasomotor drive. Hemorrhage experiments (16 ml/kg over 22 min) were
      performed in unanesthetized male Sprague-Dawley rats prepared with bilateral
      ibotenate lesions or guide cannulas directed toward the external lateral
      subnucleus of the VL-LPBN. Hemorrhage initially decreased mean arterial pressure
      (MAP) from approximately 100 mmHg control to 40-50 mmHg, and also decreased heart
      rate. In animals with sham lesions, MAP returned to 84 +/- 4 mmHg by 40 min
      posthemorrhage, and subsequent autonomic blockade with hexamethonium reduced MAP
      to 53 +/- 2 mmHg. In contrast, animals with VL-LPBN lesions remained hypotensive
      at 40 min posthemorrhage (58 +/- 4 mmHg) and hexamethonium had no effect on MAP,
      implying a deficit in sympathetic tone. VL-LPBN lesions did not alter the renin
      response or the effect of vasopressin V1 receptor blockade after hemorrhage.
      Posthemorrhage blood pressure recovery was also significantly delayed by VL-LPBN
      infusion of the ionotropic glutamate receptor antagonist kynurenic acid. Both VL
      LPBN lesions and VL-LPBN kynurenate infusion caused posthemorrhage bradycardia to
      be significantly prolonged. Bradycardia was reversed by hexamethonium or
      atropine, but did not contribute to posthemorrhage hypotension. Taken together,
      these data support the hypothesis that stimulation of VL-LPBN glutamate receptors
      mediates spontaneous blood pressure recovery by initiating restoration of
      sympathetic vasomotor drive.

PMID- 16574888
TI  - The di-leucine motif contributes to class a scavenger receptor-mediated
      internalization of acetylated lipoproteins.
AB  - OBJECTIVE: The di-leucine motif exists in the intracellular domains of certain
      cell surface receptors, participating in the receptor-mediated endocytosis. The
      present study was aimed at determining the role of the di-leucine motif in class
      A scavenger receptor (SR-A)-mediated ligand endocytosis. METHODS AND RESULTS:
      cDNA coding for a mutant (SR-A mutant N3132LM) with deletion of the di-leucine
      structure was transfected into Chinese hamster ovary (CHO) cells. Compared with
      wild-type SR-A-expressing cells, the cells expressing the SR-A mutant N3132LM
      showed a significant decrease in uptake but almost no change in binding of the SR
      A ligand acetylated low-density lipoprotein (AcLDL). Western blot analysis
      revealed coimmunoprecipitation of SR-A mutant and clathrin from the lysates of
      the mutant but not wild-type CHO cells, suggesting that AcLDL-bound SR-A mutant
      N3132LM is associated with the clathrin-coated pit of cellular membrane. Removal
      of the first 27 amino acid residues from the SR-A N-terminus further reduced
      AcLDL uptake by the cells with the di-leucine motif mutation. CONCLUSIONS: The di
      leucine motif of SR-A intracellular domain contributes to the SR-A-mediated
      cellular internalization of AcLDL. Di-leucine pair exists in the cytoplasmic
      domain of class A scavenger receptor. The cells expressing di-leucine mutants
      showed decreased uptake and unchanged binding of AcLDL. The di-leucine pair was
      not associated to coated pits. It suggests that di-leucine motif acts as a signal
      sequence to mediate SR-A into cell.

PMID- 16574889
TI  - Modulation of smooth muscle cell migration by members of the low-density
      lipoprotein receptor family.
AB  - Low-density lipoprotein receptor family members (LRs) play a key role in the
      catabolism of many membrane-associated proteins, such as complexes between
      proteinases and their receptors, in addition to being involved in lipoprotein
      metabolism as suspected by the hitherto well-established functions of low-density
      lipoprotein receptor, in a variety of tissues. Recent studies using receptor
      deficient or -overexpressing animals and cells have suggested that certain LRs
      are important regulators of the migration (and proliferation) of vascular smooth
      muscle cells (SMCs). LR expression is markedly induced in intimal or medial SMCs
      during the formation of atherosclerotic lesions. Because LRs can modulate the
      activity of the urokinase-type plasminogen activator (uPA) receptor and possibly
      of the platelet-derived growth factor (PDGF) receptor, LRs may influence the
      migration of SMCs through functional modulation of these membrane receptors.
      Therefore, SMC migration may be regulated by time-restricted expression of LRs.
      In agreement with the concept of functional interaction between LRs and membrane
      signaling receptors, a negative regulator of uPA receptor protein catabolism,
      LR11, has been identified. Statins modulate the PDGF-induced migration of intimal
      SMCs via the LR11/uPA receptor cascade. Selective modification of the LRs/uPA
      receptor/PDGF receptor systems in SMCs may be important for suppression of
      atherosclerotic plaque formation as well as for preventing intimal thickening
      after angioplasty.

PMID- 16574890
TI  - Plasma homocysteine affects fibrin clot permeability and resistance to lysis in
      human subjects.
AB  - OBJECTIVE: Homocysteine (Hcy) is a risk factor for thrombosis. We investigated a
      hypothesis that the clot permeability and its resistance to fibrinolysis is
      associated with plasma total Hcy (tHcy) in human subjects. METHODS AND RESULTS:
      We studied healthy men not taking any medication (n=76), male patients with
      advanced coronary artery disease (CAD) taking low-dose aspirin (n=33), men with
      diabetes mellitus diagnosed recently (median hemoglobin A(1c) 7.65%; n=16), and
      patients with isolated hypercholesterolemia (>7.0 mmol/L; n=15). We assessed clot
      permeability and turbidimetric lysis time as the determinants of fibrin clot
      structure. In a regression model, including age and fibrinogen, plasma tHcy was
      an independent predictor of clot permeation and fibrinolysis time in healthy
      subjects (R2=0.88, P<0.0001 and R2=0.54, P<0.0001, respectively). In CAD
      patients, tHcy and fibrinogen were stronger predictors of the permeation
      coefficient (R2=0.84; P<0.0001) than was fibrinogen alone (R2=0.66; P<0.0001),
      whereas tHcy was the only predictor of lysis time (R2=0.69; P<0.0001). Elevated
      tHcy levels observed after methionine load were not associated with any of the
      fibrin clot properties. In patients with diabetes or hypercholesterolemia, the
      influence of Hcy on permeation and, to a lesser extent, on the lysis time was
      obscured by dominant effects of glucose and cholesterol. In 20 asymptomatic men
      with hyperhomocysteinemia treated with folic acid, reduction in tHcy levels
      resulted in increased clot permeability (P=0.0002) and shorter lysis time
      (P<0.0001). CONCLUSIONS: Our results indicate that plasma tHcy predicts clot
      permeation and susceptibility to fibrinolysis in healthy men and CAD patients.
      Our data are consistent with a mechanism of thrombosis in hyperhomocysteinemia,
      which involves modification of fibrinogen by Hcy-thiolactone.

PMID- 16574891
TI  - Biological significance of decreased HSP27 in human atherosclerosis.
AB  - OBJECTIVE: Because culprit atherosclerotic plaques contain proteases, we
      hypothesized that the diminished heat shock protein 27 (HSP27) released by
      atherosclerotic plaques could be due to proteolysis. We assessed the role of
      HSP27 in human vascular smooth muscle cells (VSMCs) under proteolytic injury.
      METHODS AND RESULTS: Active plasmin is present in culprit atherosclerotic
      plaques. Recombinant HSP27 was cleaved by plasmin and this effect was prevented
      by different inhibitors. Fragments and aggregated forms of HSP27 appeared after
      incubation of mammary control endarteries with plasmin. Coincubation of
      atherosclerotic plaques with recombinant HSP27 or mammary endarteries led to
      HSP27 proteolysis. After incubation of VSMCs with plasmin, HSP27 was
      overexpressed, phosphorylated, aggregated, and redistributed from the
      cytoskeleton to the cytosol, nucleus, and cell membrane. Plasmin-induced VSMC
      apoptosis was significantly higher in VSMCs treated by HSP27 siRNA.
      Immunohistochemical analysis of atherosclerotic plaques showed that plasmin(ogen)
      and apoptotic cells are localized in the core/shoulder whereas HSP27 and VSMCs
      are mainly expressed in the cap/media. CONCLUSIONS: Extracellular HSP27 can be
      degraded by enzymes released from atherosclerotic plaques and may reflect a
      proteolytic imbalance. Intracellular HSP27 downregulation decreases VSMCs
      resistance to proteolytically-induced apoptosis. HSP27 might play a pivotal role
      in the prevention of plaque instability and rupture.

PMID- 16574892
TI  - Granulocyte colony stimulating factor directly inhibits myocardial ischemia
      reperfusion injury through Akt-endothelial NO synthase pathway.
AB  - OBJECTIVE: Granulocyte colony stimulating factor (G-CSF) has been reported
      recently to prevent cardiac remodeling and dysfunction after acute myocardial
      infarction through signal transducer and activator of transcription 3 (STAT3). In
      this study, we examined acute effects of G-CSF on the heart against ischemia
      reperfusion injury. METHODS AND RESULTS: Rat hearts were subjected to global 35
      minute ischemia and 120-minute reperfusion in Langendorff system with or without
      G-CSF (300 ng/mL). G-CSF administration was started at the onset of reperfusion.
      Triphenyltetrazolium chloride staining revealed that G-CSF markedly reduced the
      infarct size. G-CSF strongly activated Janus kinase 2 (Jak2), STAT3,
      extracellular signal-regulated kinase (ERK), Akt, and endothelial NO synthase
      (NOS) in the hearts subjected to ischemia followed by 15-minute reperfusion. The
      G-CSF-induced reduction in infarct size was abolished by inhibitors of
      phosphatidylinositol 3-kinase, Jak2, and NOS but not of mitogen-activated protein
      kinase kinase (MEK). CONCLUSIONS: These results suggest that G-CSF acts directly
      on the myocardium during ischemia-reperfusion injury and has acute nongenomic
      cardioprotective effects through the Akt-endothelial NOS pathway.

PMID- 16574893
TI  - Effects of the cholesteryl ester transfer protein inhibitor torcetrapib on
      apolipoprotein B100 metabolism in humans.
AB  - OBJECTIVE: Cholesteryl ester transfer protein (CETP) inhibition with torcetrapib
      not only increases high-density lipoprotein cholesterol levels but also
      significantly reduces plasma triglyceride, low-density lipoprotein (LDL)
      cholesterol, and apolipoprotein B (apoB) levels. The goal of the present study
      was to define the kinetic mechanism(s) by which CETP inhibition reduces levels of
      apoB-containing lipoproteins. METHODS AND RESULTS: Nineteen subjects, 9 of whom
      were pretreated with 20 mg atorvastatin, received placebo for 4 weeks, followed
      by 120 mg torcetrapib once daily for 4 weeks. Six subjects in the nonatorvastatin
      group received 120 mg torcetrapib twice daily for an additional 4 weeks. After
      each phase, subjects underwent a primed-constant infusion of deuterated leucine
      to endogenously label newly synthesized apoB to determine very low-density
      lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and LDL apoB100
      production, and fractional catabolic rates (FCRs). Once-daily 120 mg torcetrapib
      significantly reduced VLDL, IDL, and LDL apoB100 pool sizes by enhancing the FCR
      of apoB100 within each fraction. On a background of atorvastatin, 120 mg
      torcetrapib significantly reduced VLDL, IDL, and LDL apoB100 pool sizes. The
      reduction in VLDL apoB100 was associated with an enhanced apoB100 FCR, whereas
      the decreases in IDL and LDL apoB100 were associated with reduced apoB100
      production. CONCLUSIONS: These data indicate that when used alone, torcetrapib
      reduces VLDL, IDL, and LDL apoB100 levels primarily by increasing the rate of
      apoB100 clearance. In contrast, when added to atorvastatin treatment, torcetrapib
      reduces apoB100 levels mainly by enhancing VLDL apoB100 clearance and reducing
      production of IDL and LDL apoB100.

PMID- 16574894
TI  - A simple method of plaque rupture induction in apolipoprotein E-deficient mice.
AB  - OBJECTIVE: The development of a murine model of atherosclerotic plaque rupture.
      METHODS AND RESULTS: The left common carotid arteries of male apolipoprotein E
      (apoE)-deficient mice (9 weeks old) were ligated just proximal to their
      bifurcations. After 4 weeks on a standard diet, the mice received polyethylene
      cuff placement just proximal to the ligated site, and the animals were then
      processed for morphological studies at specific time points. Ligation of the
      carotid artery in apoE-deficient mice for 4 weeks induced marked intimal
      hyperplasia, which is a lipid- and collagen-rich lesion that contains a number of
      macrophages, T lymphocytes, and smooth muscle cells. Subsequently, the cuff
      placement evoked intraplaque hemorrhage and plaque rupture with fibrin(ogen)
      positive luminal thrombus in this region accompanying a decrease in collagen
      content as well as an increase in apoptotic cells in the intima within a few days
      after cuff placement. CONCLUSIONS: We demonstrated the murine model of human
      plaque rupture, which is simple, fast, and highly efficient. This model would
      help us not only to understand the mechanism of human plaque rupture but also to
      assess various already-known and as-yet-unknown agents in the future.

PMID- 16574895
TI  - Dimethylarginine dimethylaminohydrolase 2 increases vascular endothelial growth
      factor expression through Sp1 transcription factor in endothelial cells.
AB  - OBJECTIVE: Dimethylarginie dimethylaminohydrolase (DDAH) is a degrading enzyme
      for asymmetrical dimethylarginine, an endogenous NO synthase inhibitor. The
      molecular mechanism for DDAH-induced vascular endothelial growth factor (VEGF)
      expression was examined. METHODS AND RESULTS: Although the transfection of
      expression vectors for 2 isoforms of DDAH, DDAH1, or DDAH2 increased DDAH
      activity in bovine aortic endothelial cells and human umbilical vein endothelial
      cells, expression and secretion of VEGF were increased only in DDAH2-transfected
      cells. Knocking down the DDAH2 gene reduced VEGF production, and DDAH2
      overexpression enhanced both proliferation and migration of endothelial cells.
      The VEGF promoter activity was increased by DDAH2 transfection, which was not
      blocked by an NO synthase (NOS) inhibitor but required the Sp1 sites. DDAH2
      overexpression increased nuclear protein levels bound to Sp1 oligonucleotides in
      endothelial cells. Sp1 small interfering RNA blocked DDAH2-induced upregulation
      of VEGF. DDAH2 transfection increased nuclear and threonine-phosphorylation
      levels of Sp1 in a protein kinase A (PKA)-dependent manner. Protein-protein
      interaction between DDAH2 and PKA was enhanced in DDAH2-transfected cells.
      CONCLUSIONS: DDAH2 upregulated the expression of VEGF through Sp1-dependent and
      NO/NOS system-independent promoter activation. DDAH2-increased Sp1 DNA binding
      activity was PKA dependent. These mechanisms may provide a novel therapeutic
      strategy for VEGF-related vasculopathies such as atherosclerosis.

PMID- 16574896
TI  - Adiponectin is an important determinant of apoA-I catabolism.
AB  - OBJECTIVE: Plasma concentration of adiponectin is positively correlated with high
      density lipoprotein (HDL) cholesterol level. However, the role of adiponectin on
      HDL metabolism remains unknown. This prompted us to perform an in vivo kinetic
      study of apoA-I, the main apolipoprotein of HDL, using stable isotopes, in 22
      subjects with a wide range of plasma adiponectin, including 11 patients with
      metabolic syndrome (8 with type 2 diabetes, 3 without type 2 diabetes) and 11
      normal individuals. METHODS AND RESULTS: In the 22 studied subjects, plasma
      adiponectin levels ranged from 2.57 to 14.44 microg/mL and apoA-I fractional
      catabolic rate (FCR) values ranged from 0.142 to 0.340 day(-1). A strong negative
      correlation was found between adiponectin and apoA-I FCR (r=-0.66, P<0.001) in
      the whole studied population and, to a similar extent, in patients with metabolic
      syndrome (r=-0.73, P=0.010) and normal subjects (r=-0.68, P=0.020), separately.
      In multivariable analysis, apoA-I FCR was associated negatively with adiponectin
      (P=0.005) and positively with HDL triglycerides/cholesterol ratio (P=0.006), but
      not with age, sex, body mass index (BMI), waist circumference, plasma
      triglycerides, HDL cholesterol, fasting glycemia, and QUICKI. Both adiponectin
      and HDL triglycerides/cholesterol ratio explained 62% of the variance of apoA-I
      FCR and adiponectin on its own explained 43%. CONCLUSIONS: Our kinetic study
      shows a strong negative correlation between adiponectin and apoA-I FCR, which can
      explain the positive link between HDL cholesterol and adiponectin. This
      association is independent of obesity, insulin resistance, and the content of
      triglycerides within HDL particles. These data suggest that adiponectin may have
      a direct role on HDL catabolism.

PMID- 16574897
TI  - Genome-wide expression studies of atherosclerosis: critical issues in
      methodology, analysis, interpretation of transcriptomics data.
AB  - During the past 6 years, gene expression profiling of atherosclerosis has been
      used to identify genes and pathways relevant in vascular (patho)physiology. This
      review discusses some critical issues in the methodology, analysis, and
      interpretation of the data of gene expression studies that have made use of
      vascular specimens from animal models and humans. Analysis of gene expression
      studies has evolved toward the genome-wide expression profiling of large series
      of individual samples of well-characterized donors. Despite the advances in
      statistical and bioinformatical analysis of expression data sets, studies have
      not yet fully exploited the potential of gene expression data sets to obtain
      novel insights into the molecular mechanisms underlying atherosclerosis. To
      assess the potential of published expression data, we compared the data of a CC
      chemokine gene cluster between 18 murine and human gene expression profiling
      articles. Our analysis revealed that an adequate comparison is mainly hindered by
      the incompleteness of available data sets. The challenge for future vascular
      genomic profiling studies will be to further improve the experimental design,
      statistical, and bioinformatical analysis and to make data sets freely
      accessible.

PMID- 16574898
TI  - Lipoprotein lipase S447X: a naturally occurring gain-of-function mutation.
AB  - Lipoprotein lipase (LPL) hydrolyzes triglycerides in the circulation and promotes
      the hepatic uptake of remnant lipoproteins. Since the gene was cloned in 1989,
      more than 100 LPL gene mutations have been identified, the majority of which
      cause loss of enzymatic function. In contrast to this, the naturally occurring
      LPL(S447X) variant is associated with increased lipolytic function and an anti
      atherogenic lipid profile and can therefore be regarded as a gain-of-function
      mutation. This notion combined with the facts that 20% of the general population
      carries this prematurely truncated LPL and that it may protect against
      cardiovascular disease has led to extensive clinical and basic research into this
      frequent LPL mutant. It is only until recently that we begin to understand the
      molecular mechanisms that underlie the beneficial effects associated with
      LPL(S447X). This review summarizes the current literature on this interesting LPL
      variant.

PMID- 16574899
TI  - Hypercholesterolemia reduces collateral artery growth more dominantly than
      hyperglycemia or insulin resistance in mice.
AB  - OBJECTIVE: Collateral artery development (arteriogenesis), a vital compensatory
      mechanism in patients with arterial obstructive disease, may be deregulated by
      vascular risk factors, eg, diabetes or hypercholesterolemia. Here, we compared
      the effects of either disturbed glucose metabolism or disturbed lipid metabolism
      on arteriogenesis. METHODS AND RESULTS: Femoral artery occlusion was performed in
      streptozotocin(STZ)-treated mice, nonobese diabetic (NOD) mice, and insulin
      resistant Ob/Ob mice on regular diet, and APOE3*Leiden mice on different
      hypercholesterolemic diets. Angiography and laser Doppler perfusion analysis of
      hindlimbs were performed postoperatively. Surprisingly, angiographic
      arteriogenesis was not impaired in diabetic and insulin-resistant mice. Perfusion
      recovery in STZ-treated and Ob/Ob mice was only decreased by 19% and 16%,
      respectively (P<0.05). Furthermore, perfusion recovery was unchanged between high
      glycemic and mild-glycemic NOD mice. Angiographic arteriogenesis in APOE3*Leiden
      mice, however, was markedly impaired at 7 days and 14 days (P< or =0.01).
      Correspondingly, perfusion recovery was 41% decreased in APOE3*Leiden mice
      (P<0.05). There was an inverse correlation of perfusion recovery with plasma
      cholesterol (P=0.02), but not with triglyceride, free fatty acid, glucose, or
      insulin levels. CONCLUSIONS: Hypercholesterolemia reduces arteriogenesis more
      dominantly than hyperglycemia or hyperinsulinemia in mice. This suggests that a
      disturbed lipid metabolism as observed in diabetic patients might be crucial for
      the impairment of collateral formation.

PMID- 16574900
TI  - MMP-9 microsatellite polymorphism and susceptibility to carotid arteries
      atherosclerosis.
AB  - OBJECTIVE: The aims of this study were to compare a microsatellite polymorphism
      (PM) of matrix metalloproteinase (MMP)-9 in patients with carotid atherosclerosis
      and control population, and to assess the relationship between this PM and plaque
      structure. METHODS AND RESULTS: One hundred fifty patients referring to vascular
      diagnostic centers for suspected carotid atherosclerosis (at ultrasound
      examination: 110 positive, 40 negative) and controls (n=110) have been genotyped
      for MMP-9 PM. After controlling for risk factors, allelic and genotype
      frequencies were significantly different among the groups, with significant
      prevalence of long microsatellites in patients with carotid atherosclerosis. Long
      microsatellites (settled as 22 to 27 repeats) were associated with carotid
      atherosclerosis (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.9 to 9.2),
      compared with controls; an independent case control study on patients with
      coronary atherosclerosis confirmed such result. Binary logistic regression showed
      that hypertension, long microsatellites in MMP-9 PM and smoking habits were
      variables accounting for the difference between ultrasound-positive patients and
      controls. Long microsatellites were also associated to plaques with thin fibrous
      cap and echolucent core (OR, 13.1; 95% CI, 1.6 to 100). These alleles were
      slightly more represented in female patients (chi2 test=0.019; OR, 2.7; 95% CI,
      1.2 to 6) but not associated with other risk factors. Plasma MMP-9 levels were
      related neither to MMP-9 PM nor to plaque type, and were related to gender and
      extension of atherosclerosis in carotid arteries. CONCLUSIONS: The number of
      repeats (> or =22 CA) in the microsatellite of MMP-9 promoter, but not MMP-9
      plasma levels, is associated to carotid atherosclerosis and particularly to
      plaques with a thin fibrous cap.

PMID- 16574901
TI  - Monocyte chemoattractant protein-1 induces a novel transcription factor that
      causes cardiac myocyte apoptosis and ventricular dysfunction.
AB  - Monocyte chemoattractant protein-1 (MCP-1; CCL2)-mediated inflammation plays a
      critical role in the development of ischemic heart disease (IHD). However, the
      gene expression changes caused by signal transduction, triggered by MCP-1 binding
      to its receptor CCR2, and their possible role in the development of IHD are not
      understood. We present evidence that MCP-1 binding to CCR2 induces a novel
      transcription factor (MCP-induced protein [MCPIP]) that causes cell death. Gene
      microarray analysis showed that when expressed in hiuman embryonic kidney 293
      cells, MCPIP induced apoptotic gene families before causing cell death.
      Mutagenesis studies showed that the structural features required for
      transcription factor-like activity were also required for causing cell death.
      Activation of caspase-3 was detected after MCPIP transfection and Z-VAD-fmk
      partially inhibited cell death. Cardiomyocyte-targeted expression of MCP-1 in
      mice caused death by heart failure at 6 months of age. MCPIP expression increased
      in parallel with the development of ventricular dysfunction. In situ
      hybridization showed the presence of MCPIP transcripts in the cardiomyocytes and
      immunohistochemistry showed that MCPIP was associated with the cardiomyocyte
      nuclei of apoptotic cardiomyocytes. CCR2 expression in cardiomyocytes increased
      with the development of IHD. MCPIP production induced by MCP-1 binding to CCR2 in
      the cardiomyocytes is probably involved in the development of IHD in this murine
      model. MCPIP transcript levels were much higher in the explanted human hearts
      with IHD than with nonischemic heart disease. These results provide a molecular
      insight into how chronic inflammation and exposure to MCP-1 contributes to heart
      failure and suggest that MCPIP could be a potential target for therapeutic
      intervention.

PMID- 16574903
TI  - Altered S-phase kinase-associated protein-2 levels are a major mediator of cyclic
      nucleotide-induced inhibition of vascular smooth muscle cell proliferation.
AB  - Cyclic nucleotides inhibit vascular smooth muscle cell (VSMC) proliferation but
      the underlying molecular mechanisms are incompletely understood. We studied the
      role of S-phase kinase-associated protein-2 (Skp2), an F-box protein of SCFSkp2
      ubiquitin ligase responsible for polyubiquitylation of and subsequent proteolysis
      of p27Kip1, a key step leading to cell cycle progression. Skp2 mRNA and protein
      were upregulated in mitogen-stimulated VSMCs and after balloon injury in rat
      carotid arteries, where the time course and location of Skp2 expression closely
      paralleled that of proliferating cell nuclear antigen. Skp2 small interference
      RNA (siRNA) reduced Skp2 expression, increased p27Kip1 levels, and inhibited VSMC
      proliferation in vitro. cAMP-elevating agents prominently inhibited VSMC
      proliferation and Skp2 expression through inhibiting Skp2 transcription as well
      as decreasing Skp2 protein stability. Consistent with this, activation of protein
      kinase A, a downstream target of cAMP, was shown to negatively regulate focal
      adhesion kinase (FAK) phosphorylation and Skp2 expression. Adenovirus-mediated
      Skp2 expression reversed cAMP-induced p27Kip1 upregulation and rescued cAMP
      related S-phase entry inhibition up to 50%. 8-bromo-cGMP also moderately reduced
      Skp2 and cell proliferation when VSMCs were incubated with low serum
      concentration. Interestingly, we showed that 8-bromo-cGMP inhibited Skp2
      expression also through activation of protein kinase A, not protein kinase G,
      which conversely enhanced FAKY397 phosphorylation and Skp2 expression. After
      balloon injury of rat carotid arteries, local forskolin treatment significantly
      reduced FAKY397 phosphorylation, Skp2 expression, VSMC proliferation, and
      subsequent neointimal thickening. These data demonstrate for the first time that
      Skp2 is an important factor in VSMC proliferation and its inhibition by cyclic
      nucleotides.

PMID- 16574902
TI  - Absence of TRAM restricts Toll-like receptor 4 signaling in vascular endothelial
      cells to the MyD88 pathway.
AB  - Mammalian cells respond to bacterial lipopolysaccharide (LPS) through a cognate
      receptor: Toll-like receptor 4 (TLR4). The signaling pathways, which link TLR4 to
      the proinflammatory transcription factor nuclear factor kappaB (NF-kappaB), occur
      through the intracellular docking proteins MyD88 and Trif. We hypothesize that
      unlike antigen-presenting cells, vascular endothelial cells (ECs) lack the Trif
      protein TRAM and are therefore incapable of eliciting Trif-dependent immune
      responses to LPS. Stimulation of wild-type mice with LPS leads to the activation
      of NF-kappaB in ECs and macrophages in vitro and in vivo. In contrast to
      macrophages, LPS did not activate endothelial NF-kappaB or NF-kappaB-dependent
      genes in MyD88(-/-) mice, suggesting the absence of a functional Trif pathway in
      vascular ECs. Indeed, the Trif-dependent gene cxcl10 was not expressed in ECs
      after LPS stimulation. This correlated with diminished expression of the Trif
      accessory TIR protein TRAM in ECs. Overexpression of TRAM cDNA in ECs
      reconstituted LPS-induced Trif-dependent NF-kappaB activation and cxcl10 promoter
      activity. The functional absence of TRAM in vascular ECs restricts TLR4 signaling
      to MyD88-dependent pathway. This is in contrast to macrophages, which respond to
      LPS via both Trif- and MyD88-dependent pathways. These findings indicate that
      vascular ECs do not express the Trif-dependent gene subset. This implies that
      these genes may be dispensable for the endothelial response to bacterial
      infection and play no role in the endothelial contribution to the development of
      atherosclerosis.

PMID- 16574904
TI  - Urocortin-induced decrease in Ca2+ sensitivity of contraction in mouse tail
      arteries is attributable to cAMP-dependent dephosphorylation of MYPT1 and
      activation of myosin light chain phosphatase.
AB  - Urocortin, a vasodilatory peptide related to corticotropin-releasing factor, may
      be an endogenous regulator of blood pressure. In vitro, rat tail arteries are
      relaxed by urocortin by a cAMP-mediated decrease in myofilament Ca2+ sensitivity
      through a still unclear mechanism. Here we show that contraction of intact mouse
      tail arteries induced with 42 mmol/L KCl or 0.5 micromol/L noradrenaline was
      associated with a approximately 2-fold increase in the phosphorylation of the
      regulatory subunit of myosin phosphatase (SMPP-1M), MYPT1, at Thr696, which was
      reversed in arteries relaxed with urocortin. Submaximally (pCa 6.1) contracted
      mouse tail arteries permeabilized with alpha-toxin were relaxed with urocortin by
      39+/-3% at constant [Ca2+], which was associated with a decrease in myosin light
      chain (MLC20Ser19), MYPT1Thr696, and MYPT1Thr850 phosphorylation by 60%, 28%, and
      52%, respectively. The Rho-associated kinase (ROK) inhibitor Y-27632 decreased
      MYPT1 phosphorylation by a similar extent. Inhibition of PP-2A with 3 nmol/L
      okadaic acid had no effect on MYPT1 phosphorylation, whereas inhibition of PP-1
      with 3 micromol/L okadaic acid prevented dephosphorylation. Urocortin increased
      the rate of dephosphorylation of MLC20Ser19 approximately 2.2-fold but had no
      effect on the rate of contraction under conditions of, respectively, inhibited
      kinase and phosphatase activities. The effect of urocortin on MLC20Ser19 and
      MYPT1 phosphorylation was blocked by Rp-8-CPT-cAMPS and mimicked by Sp-5,6-DCl
      cBIMPS. In summary, these results provide evidence that Ca(2+)-independent
      relaxation by urocortin can be attributed to a cAMP-mediated increased activity
      of SMPP-1M which at least in part is attributable to a decrease in the inhibitory
      phosphorylation of MYPT1.

PMID- 16574905
TI  - Critical roles of muscle-secreted angiogenic factors in therapeutic
      neovascularization.
AB  - The discovery of bone marrow-derived endothelial progenitors in the peripheral
      blood has promoted intensive studies on the potential of cell therapy for various
      human diseases. Accumulating evidence has suggested that implantation of bone
      marrow mononuclear cells effectively promotes neovascularization in ischemic
      tissues. It has also been reported that the implanted cells are incorporated not
      only into the newly formed vessels but also secrete angiogenic factors. However,
      the mechanism by which cell therapy improves tissue ischemia remains obscure. We
      enrolled 29 "no-option" patients with critical limb ischemia and treated ischemic
      limbs by implantation of peripheral mononuclear cells. Cell therapy using
      peripheral mononuclear cells was very effective for the treatment of limb
      ischemia, and its efficacy was associated with increases in the plasma levels of
      angiogenic factors, in particular interleukin-1beta (IL-1beta). We then examined
      an experimental model of limb ischemia using IL-1beta-deficient mice.
      Implantation of IL-1beta-deficient mononuclear cells improved tissue ischemia as
      efficiently as that of wild-type cells. Both wild-type and IL-1beta-deficient
      mononuclear cells increased expression of IL-1beta and thus induced angiogenic
      factors in muscle cells of ischemic limbs to a similar extent. In contrast,
      inability of muscle cells to secrete IL-1beta markedly reduces induction of
      angiogenic factors and impairs neovascularization by cell implantation. Implanted
      cells do not secret angiogenic factors sufficient for neovascularization but,
      instead, stimulate muscle cells to produce angiogenic factors, thereby promoting
      neovascularization in ischemic tissues. Further studies will allow us to develop
      more effective treatments for ischemic vascular disease.

PMID- 16574906
TI  - Endostatin, the proteolytic fragment of collagen XVIII, induces vasorelaxation.
AB  - Collagen XVIII is an important component of the extracellular matrix and is
      expressed in basement membranes. Its degradation results in the generation of
      endostatin claimed to possess antiangiogenic activity. To date, only limited
      knowledge exists with regard to the cellular signaling of this molecule. We show
      in single-cell measurements using the Ca2+ indicator fura-2 acetoxy methylester
      (fura-2 AM) and the nitric oxide (NO) indicator 4,5-diaminofluorescein diacetate
      that application of endostatin (ES) (5 pmol/L, 100 ng/mL) induced Ca2+ spikes and
      an increase of NO production in human and murine endothelial cells. The NO
      response was independent of an increase in cytosolic Ca2+ and blocked by the
      endothelial NO synthase (eNOS) inhibitor NG-nitro-L-arginine methyl ester and by
      incubation with pertussis toxin known to inhibit G(i/o) proteins. The
      physiological relevance of this novel signaling pathway of ES was assessed with
      isometric force measurements in large and small arteries of mouse. Physiological
      concentrations of ES were found to decrease vascular tone in an endothelium
      dependent manner. This occurred via an Arg-Gly-Asp (RGD) peptide-independent
      pathway through activation of G(i/o) proteins, phosphatidylinositol 3-kinase,
      Akt, and eNOS. We conclude that the proteolytic matrix fragment ES is a prominent
      vasorelaxing agent. Because ES is constantly released into the blood, it is a
      novel regulator of blood pressure and, therefore, represents an interesting
      pharmacological target.

PMID- 16574907
TI  - Ablation of cardiac myosin-binding protein-C accelerates stretch activation in
      murine skinned myocardium.
AB  - Cardiac myosin binding protein-C (cMyBP-C) is a thick filament accessory protein
      that binds tightly to myosin, but despite evidence that mutations in the cMyBP-C
      gene comprise a frequent cause of hypertrophic cardiomyopathy, relatively little
      is known about the role(s) of cMyBP-C in myocardium. Based on earlier studies
      demonstrating the potential importance of stretch activation in cardiac
      contraction, we examined the effects of cMyBP-C on the stretch activation
      responses of skinned ventricular preparations from wild-type (WT) and homozygous
      cMyBP-C knockout mice (cMyBP-C(-/-)) previously developed in our laboratory.
      Sudden stretch of skinned myocardium during maximal or submaximal Ca2+
      activations resulted in an instantaneous increase in force that quickly decayed
      to a minimum and was followed by a delayed redevelopment of force (ie, stretch
      activation) to levels greater than prestretch force. Ablation of cMyBP-C
      dramatically altered the stretch activation response, ie, the rates of force
      decay and delayed force transient were accelerated compared with WT myocardium.
      These results suggest that cMyBP-C normally constrains the spatial position of
      myosin cross-bridges, which, in turn, limits both the rate and extent of
      interaction of cross-bridges with actin. We propose that ablation of cMyBP-C
      removes this constraint, increases the likelihood of cross-bridge binding to
      actin, and speeds the rate of delayed force development following stretch.
      Regardless of the specific mechanism, acceleration of cross-bridge cycling in
      cMyBP-C(-/-) myocardium could account for the abbreviation of systolic ejection
      in this mouse as a direct consequence of premature stretch activation of
      ventricular myocardium.

PMID- 16574908
TI  - Impact of TASK-1 in human pulmonary artery smooth muscle cells.
AB  - The excitability of pulmonary artery smooth muscle cells (PASMC) is regulated by
      potassium (K+) conductances. Although studies suggest that background K+ currents
      carried by 2-pore domain K+ channels are important regulators of resting membrane
      potential in PASMC, their role in human PASMC is unknown. Our study tested the
      hypothesis that TASK-1 leak K+ channels contribute to the K+ current and resting
      membrane potential in human PASMC. We used the whole-cell patch-clamp technique
      and TASK-1 small interfering RNA (siRNA). Noninactivating K+ current performed by
      TASK-1 K+ channels were identified by current characteristics and inhibition by
      anandamide and acidosis (pH 6.3), each resulting in significant membrane
      depolarization. Moreover, we showed that TASK-1 is blocked by moderate hypoxia
      and activated by treprostinil at clinically relevant concentrations. This is
      mediated via protein kinase A (PKA)-dependent phosphorylation of TASK-1. To
      further confirm the role of TASK-1 channels in regulation of resting membrane
      potential, we knocked down TASK-1 expression using TASK-1 siRNA. The knockdown of
      TASK-1 was reflected by a significant depolarization of resting membrane
      potential. Treatment of human PASMC with TASK-1 siRNA resulted in loss of
      sensitivity to anandamide, acidosis, alkalosis, hypoxia, and treprostinil. These
      results suggest that (1) TASK-1 is expressed in human PASMC; (2) TASK-1 is
      hypoxia-sensitive and controls the resting membrane potential, thus implicating
      an important role for TASK-1 K+ channels in the regulation of pulmonary vascular
      tone; and (3) treprostinil activates TASK-1 at clinically relevant concentrations
      via PKA, which might represent an important mechanism underlying the vasorelaxing
      properties of prostanoids and their beneficial effect in vivo.

PMID- 16574909
TI  - Scavenger receptor BI prevents nitric oxide-induced cytotoxicity and endotoxin
      induced death.
AB  - Nitric oxide (NO)-induced oxidative stress contributes to a variety of diseases.
      Although numerous mechanisms have been described controlling the production of
      NO, the mechanisms to prevent NO-induced cytotoxicity after NO synthesis are
      largely unknown. Here we report that scavenger receptor BI (SR-BI) prevents NO
      induced cytotoxicity. Using CHO cell lines expressing wild-type and single-site
      mutant SR-BI protein, we demonstrate that SR-BI prevents NO-induced cytotoxicity
      and that a highly conserved CXXS redox motif is required for the anti-NO
      cytotoxicity activity of SR-BI. Using genetically manipulated mice, we
      demonstrate that SR-BI-null mice have a 3- to 4-fold increase in tyrosine
      nitrated proteins in aorta and liver compared with wild-type littermates,
      indicating that expression of SR-BI prevents peroxynitrite formation in vivo.
      Using lipopolysacharide (LPS)-challenged mice as an in vivo model of NO-induced
      cytotoxicity, we found that a single dose of LPS (120,000 U/g IP) induced 90%
      fatality of SR-BI-null mice within 3 days, whereas all of the wild-type
      littermates survived (n=20), demonstrating that SR-BI is highly protective
      against NO cytotoxicity in vivo. Importantly, SR-BI prevents LPS-induced death
      without eliminating NO production, suggesting that SR-BI prevents NO-induced
      cytotoxicity post-NO synthesis. Our study describes a novel observation that may
      shed new light on the treatment of nitric oxidative stress-associated diseases,
      such as septic shock.

PMID- 16574910
TI  - GATA4 and the two sides of gene expression reprogramming.

PMID- 16574911
TI  - Coupled and uncoupled NOS: separate but equal? Uncoupled NOS in endothelial cells
      is a critical pathway for intracellular signaling.

PMID- 16574912
TI  - Nuclear signaling in smooth muscle cells: cyclic nucleotide phosphodiesterase 1A
      moves in.

PMID- 16574913
TI  - Fishing for function in zebrafish.

PMID- 16574914
TI  - The Rac and Rho hall of fame: a decade of hypertrophic signaling hits.
AB  - Over the last decade, the Rho family GTPases have gained considerable recognition
      as powerful regulators of actin cytoskeletal organization. As with many high
      profile signal transducers, these molecules soon attracted the attention of the
      cardiovascular research community. Shortly thereafter, two prominent members
      known as RhoA and Rac1 were linked to agonist-induced gene expression and
      myofilament organization using the isolated cardiomyocyte cell model. Subsequent
      creation of transgenic mouse lines provided evidence for more complex roles of
      RhoA and Rac1 signaling. Clues from in vitro and in vivo studies suggest the
      involvement of numerous downstream targets of RhoA and Rac1 signaling including
      serum response factor, NF-kappaB, and other transcription factors, myofilament
      proteins, ion channels, and reactive oxygen species generation. Which of these
      contribute to the observed phenotypic effects of enhanced RhoA and Rac activation
      in vivo remain to be determined. Current research efforts with a more
      translational focus have used statins or Rho kinase blockers to assess RhoA and
      Rac1 as targets for interventional approaches to blunt hypertrophy or heart
      failure. Generally, salutary effects on remodeling and ischemic damage are
      observed, but the broad specificity and multiple cellular targets for these drugs
      within the myocardium demands caution in interpretation. In this review, we
      assess the evolution of knowledge related to Rac1 and RhoA in the context of
      hypertrophy and heart failure and highlight the direction that future exploration
      will lead.

PMID- 16574915
TI  - Vesicular trafficking of tyrosine kinase receptors and associated proteins in the
      regulation of signaling and vascular function.
AB  - Receptor tyrosine kinases (RTKs) play a pivotal role in the development and
      function of the cardiovascular system. Ligand-activated RTKs promote numerous
      downstream signal transduction pathways that lead to vascular permeability, as
      well as proliferation, migration, and differentiation of vascular endothelia and
      smooth muscle cells. Ligand binding also promotes internalization of the
      activated receptors either to downregulate the signaling via degradation of the
      ligand/receptor complex or to signal from endosomes. However, the outcomes of
      receptor internalization via clathrin-dependent or caveolar pathways and
      trafficking mechanisms are incompletely clarified in vascular systems. Activity
      modulation through endocytosis and vesicular trafficking significantly impacts
      downstream targets of RTKs such as endothelial nitric oxide synthase (eNOS) and
      VE-cadherin. RTKs and their associated targets are also transported to the
      nucleus, where they may directly impact nuclear signaling. Although the nuclear
      transport pathways are just beginning to be unraveled, it appears that
      endocytosis and vesicular trafficking are involved. In this review, we discuss
      the mechanisms by which activated RTKs and the downstream targets eNOS and VE
      cadherin may be internalized and transported to various intracellular
      compartments. How localization and interacting proteins impact protein function
      and influence signaling is an important theme, as is the potential for modulating
      signaling through therapeutic targeting of activated receptors and components of
      the endocytic machinery.

PMID- 16574916
TI  - Rho GTPases and leukocyte adhesion receptor expression and function in
      endothelial cells.
AB  - Rho family GTPases are key signal transducers that regulate cell adhesion and
      migration and a variety of other cellular responses, including changes in gene
      expression. In this review, we discuss how Rho GTPases regulate signaling by
      endothelial cell receptors involved in leukocyte extravasation. First, Rho
      GTPases affect the expression of some leukocyte adhesion molecules on endothelial
      cells, such as intracellular adhesion molecule-1 and E-selectin, that can be
      induced by proinflammatory mediators, hypoxia, or shear stress. Second, Rho
      GTPases are activated by engagement of several leukocyte adhesion receptors and
      contribute to both early morphological changes and subsequent alterations in gene
      expression. Rho GTPases are therefore candidate targets for inhibiting leukocyte
      transendothelial migration in heart disease and chronic inflammatory disorders.

PMID- 16574917
TI  - Compatibility of carotid stenting and cardiac surgery.

PMID- 16574918
TI  - Lifetime cost of ischemic stroke in Germany: results and national projections
      from a population-based stroke registry: the Erlangen Stroke Project.
AB  - BACKGROUND AND PURPOSE: The number of stroke patients and the healthcare costs of
      strokes are expected to rise. The objective of this study was to determine the
      direct costs of first ischemic stroke and to estimate the expected increase in
      costs in Germany. METHODS: An incidence-based, bottom-up, direct-cost-of-ischemic
      stroke study from the third-party payer's perspective was performed,
      incorporating 10-year survival data and 5-year resource use data from the
      Erlangen Stroke Registry. Discounted lifetime year 2004 costs per case were
      obtained and applied to the expected age and sex evolution of the German resident
      population in the period 2006 to 2025. RESULTS: The overall cost per first-year
      survivor of first-ever ischemic stroke was estimated to be 18,517 euros (EUR).
      Rehabilitation accounted for 37% of this cost, whereas in subsequent years
      outpatient care was the major cost driver. Discounted lifetime cost per case was
      43,129 EUR overall and was higher in men (45,549 EUR) than in women (41,304 EUR).
      National projections for the period 2006 to 2025 showed 1.5 million and 1.9
      million new cases of ischemic stroke in men and women, respectively, at a present
      value of 51.5 and 57.1 billion EUR, respectively. CONCLUSIONS: The number of
      stroke patients and the healthcare costs of strokes in Germany will rise
      continuously until the year 2025. Therefore, stroke prevention and reduction of
      stroke-related disability should be made priorities in health planning policies.

PMID- 16574919
TI  - Cerebral blood flow threshold of ischemic penumbra and infarct core in acute
      ischemic stroke: a systematic review.
AB  - BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) reduction below critical
      thresholds discriminates between irreversible infarct core, penumbra, and benign
      oligemia (penumbra that recovers spontaneously). Thresholds are based on animal
      studies, and their diagnostic accuracy in humans has never been established. The
      purpose of this study was to assess the evidence available on CBF thresholds for
      infarct core and penumbra in adult stroke patients. METHODS: Electronic database
      searching using Medline, Embase and the Cochrane Library, crosschecking of
      references, and contact with experts and authors of primary studies was used.
      Studies on adult stroke patients were included if they compared CBF measurements
      with a diagnostic gold standard (follow-up brain CT/MRI), and reported CBF
      thresholds. Two reviewers independently extracted the data and assessed study
      quality. RESULTS: A meta-analysis could not be carried out because of
      insufficient data. The optimal reported CBF thresholds varied widely, from 14.1
      to 35.0 and from 4.8 to 8.4 mL/100 g per minute for penumbra and infarct core,
      respectively. CONCLUSIONS: The use of CBF thresholds in commercial software for
      imaging methods cannot be recommended without further evaluation.

PMID- 16574920
TI  - The arctic ground squirrel brain is resistant to injury from cardiac arrest
      during euthermia.
AB  - BACKGROUND AND PURPOSE: Hetereothermic mammals tolerate hypoxia during euthermy
      and torpor, and evidence suggests this tolerance may extend beyond hypoxia to
      cerebral ischemia. During hibernation, CA1 hippocampal neurons endure extreme
      fluctuations in cerebral blood flow during transitions into and out of torpor as
      well as reductions in cerebral blood flow during torpor. In vitro studies
      likewise show evidence of ischemia tolerance in hippocampal slices harvested from
      euthermic ground squirrels; however, no studies have investigated tolerance in a
      clinically relevant model of in vivo global cerebral ischemia. The purpose of the
      present study was to test the hypothesis that the euthermic Arctic ground
      squirrel (AGS; Spermophillus parryii) is resistant to injury from asphyxial
      cardiac arrest (CA). METHODS: Estrous-matched female rats were used as a positive
      control. Female euthermic AGS and rats were subjected to 8-minute CA. At the end
      of 7 days of reperfusion, AGS and rats were fixed for histopathological
      assessment. RESULTS: In rats subjected to CA, the number of ischemic neurons was
      significantly higher (P<0.001) compared with control rats in hippocampus and
      striatum. Cortex was mildly injured. Surprisingly, neuronal counts in AGS were
      not significantly different in CA and control groups in these brain regions.
      CONCLUSIONS: These data demonstrate that AGS are remarkably tolerant to global
      cerebral ischemia during euthermia. A better understanding of the mechanisms by
      which AGS tolerate severe reductions in blood flow during euthermia may provide
      novel neuroprotective strategies that may translate into significant improvements
      in human patient outcomes after CA.

PMID- 16574921
TI  - Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to
      intracranial aneurysm.
AB  - BACKGROUND AND PURPOSE: Previous studies have shown positive evidence of linkage
      of the intracranial aneurysm (IA) at chromosome 7q11, 17cen, 19q13, and Xp22.
      These regions contain elastin (ELN), nitric oxide synthetase 2A (NOS2A),
      apolipoprotein E (APOE), and angiotensin-I converting enzyme 2 (ACE2), which are
      considered to be promising candidate genes for IA. We aimed to examine the
      association of single-nucleotide polymorphisms (SNPs) with IA in these candidate
      genes. METHODS: To identify polymorphisms in NOS2A and ACE2, all exons and exon
      intron boundaries were screened by direct sequencing in 30 randomly selected
      controls. The program tagSNPs was used to select an optimal set of haplotype
      tagging SNPs. For ELN and APOE, SNPs were selected from previous reports. These
      selected SNPs were then genotyped in 362 cases with IA and 332 residential area
      matched controls. THESIAS software was used to investigate the association of
      alleles and haplotypes with IA by adjusting with covariates. RESULTS: We
      genotyped 8 SNPs in ELN, 8 SNPs in NOS2A, 3 epsilon alleles in APOE and 1 SNP in
      ACE2. No alleles or haplotypes of 4 candidate genes revealed any significant
      association with IA. CONCLUSIONS: Investigated polymorphisms in this study were
      not associated with IA.

PMID- 16574922
TI  - Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of
      safety and efficacy 3 to 9 hours after stroke onset.
AB  - BACKGROUND AND PURPOSE: Desmoteplase is a novel plasminogen activator with
      favorable features in vitro compared with available agents. This study evaluated
      safety and efficacy of intravenous (IV) desmoteplase in patients with
      perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic
      stroke. METHODS: DEDAS was a placebo-controlled, double-blind, randomized, dose
      escalation study investigating doses of 90 microg/kg and 125 microg/kg
      desmoteplase. Eligibility criteria included baseline National Institute of Health
      Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion
      mismatch. The safety end point was the rate of symptomatic intracranial
      hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours
      after treatment and good clinical outcome at 90 days. The primary analyses were
      intent-to-treat. Before unblinding, a target population, excluding patients
      violating specific MRI criteria, was defined. RESULTS: Thirty-seven patients were
      randomized and received treatment (intent-to-treat; placebo: n=8; 90 microg/kg:
      n=14; 125 microg/kg: n=15). No symptomatic intracranial hemorrhage occurred.
      Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2%
      (2.3; 51.8) of patients treated with 90 microg/kg desmoteplase, and 53.3% (26.6;
      78.7) of patients treated with 125 microg/kg desmoteplase. Good clinical outcome
      at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1)
      treated with 90 microg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125
      microg/kg desmoteplase. In the target population (n=25), the difference compared
      with placebo increased and was statistically significant for good clinical
      outcome with 125 microg/kg desmoteplase (P=0.022). CONCLUSIONS: Treatment with IV
      desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of
      125 microg/kg desmoteplase appeared to improve clinical outcome, especially in
      patients fulfilling all MRI criteria. The results of DEDAS generally support the
      results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).

PMID- 16574923
TI  - Patient behavior immediately after transient ischemic attack according to
      clinical characteristics, perception of the event, and predicted risk of stroke.
AB  - BACKGROUND AND PURPOSE: Little research has been done on patients' behavior after
      transient ischemic attack (TIA). Recent data on the high early risk of stroke
      after TIA mean that emergency action after TIA is essential for effective
      secondary prevention. We therefore studied patients' behavior immediately after
      TIA according to their perceptions, clinical characteristics, and predicted
      stroke risk. METHODS: Consecutive patients with TIA participating in the Oxford
      Vascular Study or attending dedicated hospital clinics in Oxfordshire, UK, were
      interviewed. Predicted stroke risk was calculated using 2 validated scores.
      RESULTS: Of 241 patients, 107 (44.4%) sought medical attention within hours of
      the event, although only 24 of these attended the emergency department. A total
      of 107 (44.4%) delayed seeking medical attention for > or =1 day. Correct
      recognition of symptoms (42.2% of patients) was not associated with less delay.
      However, patients with motor symptoms or duration of symptoms > or =1 hour were
      more likely to seek emergency attention (hazard ratio, 2.1; 95% CI, 1.4 to 3.2;
      P=0.00005), as were those at higher predicted stroke risk (P=0.001). The other
      main correlate with delay was the day of the week on which the TIA occurred
      (P<0.001), with greater delays at the weekend. Delay was unrelated to age, sex,
      or other vascular risk factors. CONCLUSIONS: Many patients delay seeking medical
      attention after a TIA irrespective of correct recognition of symptoms, although
      patients at higher predicted risk of stroke do act more quickly. Public education
      about both the urgency and nature of TIA is required.

PMID- 16574924
TI  - Reduced risk factors for vascular disorders in Parkinson disease patients: a case
      control study.
AB  - BACKGROUND AND PURPOSE: Sympathetic hyperactivity is a contributing cause of
      vascular disorders because it increases blood pressure, blood sugar, and blood
      lipids. Pervasive compromise of the central and peripheral autonomic nervous
      systems is common in idiopathic Parkinson disease (IPD) resulting in reduced
      sympathetic and parasympathetic function. We hypothesized that IPD was associated
      with reduced prevalence of cardiovascular disease risk factors as a result of
      reduced sympathetic activity. METHODS: We performed a retrospective case-control
      study on 178 newly diagnosed consecutive IPD patients, and 533 age- (+/-3 years)
      and sex-matched controls with other neurological diseases seen over the same
      period at the same hospital. For each case and control the following were noted
      on admission: smoking, diabetes, hypertension, body mass index, serum glucose,
      plasma cholesterol, triglycerides and total lipid levels, and blood pressure.
      RESULTS: Diabetes, history of smoking, high blood pressure, high blood glucose,
      high blood cholesterol, and triglycerides were significantly less frequent in IPD
      than controls. CONCLUSIONS: IDP is a natural model of impaired hypothalamic
      pituitary-adrenal axis activity and generalized sympathetic denervation. We
      interpret the association of untreated IPD with reduced vascular diseases risk
      factors as attributable to reduced autonomic activity, suggesting that autonomic
      hyperactivity may be involved in the pathogenesis of vascular disorders.

PMID- 16574926
TI  - How critical is fibrous cap thickness to carotid plaque stability? A flow-plaque
      interaction model.
AB  - BACKGROUND AND PURPOSE: Acute cerebral ischemic events are associated with
      rupture of vulnerable carotid atheroma and subsequent thrombosis. Factors such as
      luminal stenosis and fibrous cap thickness have been thought to be important risk
      factors for plaque rupture. We used a flow-structure interaction model to
      simulate the interaction between blood flow and atheromatous plaque to evaluate
      the effect of the degree of luminal stenosis and fibrous cap thickness on plaque
      vulnerability. METHODS: A coupled nonlinear time-dependent model with a flow
      plaque interaction simulation was used to perform flow and stress/strain analysis
      in a stenotic carotid artery model. The stress distribution within the plaque and
      the flow conditions within the vessel were calculated for every case when varying
      the fibrous cap thickness from 0.1 to 2 mm and the degree of luminal stenosis
      from 10% to 95%. A rupture stress of 300 kPa was chosen to indicate a high risk
      of plaque rupture. A 1-sample t test was used to compare plaque stresses with the
      rupture stress. RESULTS: High stress concentrations were found in the plaques in
      arteries with >70% degree of stenosis. Plaque stresses in arteries with 30% to
      70% stenosis increased exponentially as fibrous cap thickness decreased. A
      decrease of fibrous cap thickness from 0.4 to 0.2 mm resulted in an increase of
      plaque stress from 141 to 409 kPa in a 40% degree stenotic artery. CONCLUSIONS:
      There is an increase in plaque stress in arteries with a thin fibrous cap. The
      presence of a moderate carotid stenosis (30% to 70%) with a thin fibrous cap
      indicates a high risk for plaque rupture. Patients in the future may be risk
      stratified by measuring both fibrous cap thickness and luminal stenosis.

PMID- 16574927
TI  - Multiple mechanisms underlying the neuroprotective effects of antiepileptic drugs
      against in vitro ischemia.
AB  - BACKGROUND AND PURPOSE: The possible neuroprotective effects of classic and new
      antiepileptic drugs on the electrophysiological changes induced by in vitro
      ischemia on striatal neurons were investigated. In particular, the aim of the
      study was to correlate the putative neuroprotective effects with the action of
      these drugs on fast sodium (Na+) and high-voltage-activated (HVA) calcium (Ca2+)
      currents. METHODS: Extracellular field potentials were recorded from rat
      corticostriatal brain-slice preparations. In vitro ischemia was delivered by
      switching to an artificial cerebrospinal fluid solution in which glucose and
      oxygen were omitted. Na+ and HVA Ca2+ currents were analyzed by whole-cell patch
      clamp recordings from acutely isolated rat striatal neurons. Excitatory
      postsynaptic potential was measured following synaptic stimulation in
      corticostriatal slices by sharp intracellular microelectrodes. RESULTS:
      Neuroprotection against in vitro ischemia was observed in slices treated with
      carbamazepine (CBZ), valproic acid (VPA), and topiramate (TPM), whereas it was
      not achieved by using levetiracetam (LEV). Fast Na+ conductances were inhibited
      by CBZ and TPM, whereas VPA and LEV showed no effect. HVA Ca2+ conductances were
      reduced by CBZ, TPM, and LEV. VPA had no effect on this current. All
      antiepileptic drugs induced a small reduction of excitatory postsynaptic
      potential amplitude at concentrations higher than 100 microm without changes of
      paired-pulse facilitation. CONCLUSIONS: The concomitant inhibition of fast Na+
      and HVA Ca2+ conductances is critically important for the neuroprotection,
      whereas the presynaptic inhibition on glutamate transmission does not seem to
      play a major role.

PMID- 16574928
TI  - The influence of hypothermia on outcome after intracerebral hemorrhage in rats.
AB  - BACKGROUND AND PURPOSE: Late hypothermia (HYPO) reduces injury after collagenase
      induced intracerebral hemorrhage (ICH), whereas early HYPO does not because it
      exacerbates the protracted bleeding that occurs in this model. We hypothesized
      that early HYPO would not increase bleeding after whole blood infusion and thus
      expected early HYPO to improve outcome through reducing secondary consequences of
      ICH (eg, inflammation). METHODS: Autologous blood (100 microL) was infused into
      the striatum. Rats were maintained at normothermia or subjected to mild (33
      degrees C to 35 degrees C) HYPO for 2 days starting 1 (HYPO-1) or 4 hours (HYPO
      4) after ICH. Hematoma volume was measured at 12 hours to determine whether HYPO
      1 aggravated bleeding. We measured blood-brain barrier (BBB) disruption and edema
      2 days after ICH in all groups. At 4 days, we counted degenerating neurons,
      neutrophils, and iron-positive cells (eg, macrophages) in the lesioned
      hemisphere. Recovery was assessed using several behavioral tests (ie, staircase
      reaching task, ladder walking task, limb use cylinder test) over 7 or 30 days, at
      which time we quantified lesion volume. RESULTS: HYPO did not increase bleeding.
      Both HYPO treatments reduced BBB disruption and infiltration of inflammatory
      cells. HYPO-1 treatment modestly reduced edema and provided limited to no
      functional benefit in the behavioral tests. HYPO did not affect lesion volume.
      CONCLUSIONS: HYPO reduced edema, BBB disruption, and inflammation. Although
      encouraging, HYPO treatment must be improved so that histological and functional
      benefit are obtained before clinical investigation. Otherwise clinical failure is
      anticipated.

PMID- 16574929
TI  - Not all patients with atrial fibrillation-associated ischemic stroke can be
      started on anticoagulant therapy.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke patients in atrial fibrillation (AF) have
      a 10% to 20% risk of recurrent stroke. Warfarin reduces this risk by two thirds.
      However, warfarin is underutilized in this patient group. We performed a
      prospective study to determine the reasons why warfarin is not started in these
      patients. METHODS: All patients with AF-associated ischemic stroke over a 12
      month period were identified. Demographic and other data, including whether
      warfarin was commenced or recommended at discharge, and if not why not, were
      recorded. RESULTS: Ninety-three of 412 (23%) ischemic stroke patients had
      paroxysmal or permanent AF. Of these patients, 17 (18%) died, 48 (52%) were
      discharged home, and 28 (30%) were discharged to institutional care. Only 13 of
      64 (20%) patients with known AF were taking warfarin at stroke onset. Warfarin
      was started (or recommended) in 35 of 76 (46%) survivors. Of those not commenced
      on warfarin, 32 (78%) were dependent (P<0.001) and 23 (56%) were discharged to
      institutional care (P<0.001). Warfarin was not started because of severe
      disability and frailty in 13 (32%), risk of falls in 12 (30%), and limited life
      expectancy in 4 (10%). CONCLUSIONS: In this cohort of patients with AF, warfarin
      was primarily underutilized before stroke onset, and it was too late to use
      anticoagulation, in approximately half, once a stroke had occurred. The decision
      to start or continue anticoagulation requires clinical judgment and should be
      made on a case by case basis after a complete risk benefit assessment.

PMID- 16574930
TI  - Deletion of cellular prion protein results in reduced Akt activation, enhanced
      postischemic caspase-3 activation, and exacerbation of ischemic brain injury.
AB  - BACKGROUND AND PURPOSE: The physiological function of cellular prion protein
      (PrPc) is not yet understood. Recent findings suggest that PrPc may have
      neuroprotective properties, and its absence increases susceptibility to neuronal
      injury. The purpose of this study was to elucidate the role of PrPc in ischemic
      brain injury in vivo. METHODS: PrP knockout (Prnp(0/0)) and Prnp(+/+) wild-type
      (WT) mice were subjected to 60-minute transient or permanent focal cerebral
      ischemia followed by infarct volume analysis 24 hours after lesion. To identify
      effects of PrPc deletion on mechanisms regulating ischemic cell death, expression
      analysis of several proapoptotic and antiapoptotic proteins was performed at 6
      and 24 hours after transient ischemia and in nonischemic controls using Western
      blot or immunohistochemistry. RESULTS: Prnp(0/0) mice displayed significantly
      increased infarct volumes after both transient or permanent ischemia when
      compared with WT animals (70.2+/-23 versus 13.3+/-4 mm3; 119.8+/-24 versus 86.4+/
      25 mm3). Expression of phospho-Akt (Ser473) was significantly reduced in
      Prnp(0/0) compared with WT animals both early after ischemia and in sham
      controls. Furthermore, postischemic caspase-3 activation was significantly
      enhanced in the basal ganglia and the parietal cortex of Prnp(0/0) mice. In
      contrast, expression of total Akt, Bax, and Bcl-2 did not differ between both
      groups. CONCLUSIONS: These results demonstrate that PrPc deletion impairs the
      antiapoptotic phosphatidylinositol 3-kinase/Akt pathway by resulting in reduced
      postischemic phospho-Akt expression, followed by enhanced postischemic caspase-3
      activation, and aggravated neuronal injury after transient and permanent cerebral
      ischemia.

PMID- 16574931
TI  - Ischemic thresholds for gray and white matter: a diffusion and perfusion magnetic
      resonance study.
AB  - BACKGROUND AND PURPOSE: Although gray matter (GM) and white matter (WM) have
      differing neurochemical responses to ischemia in animal models, it is unclear
      whether this translates into differing thresholds for infarction. We studied this
      issue in ischemic stroke patients using magnetic resonance (MR) techniques.
      METHODS: MR studies were performed in patients with acute hemispheric ischemic
      stroke occurring within 24 hours and at 3 months. Cerebral blood flow (CBF),
      cerebral blood volume (CBV), mean transit time (MTT), and apparent diffusion
      coefficient (ADC) were calculated. After segmentation based on a probabilistic
      map of GM and WM, tissue-specific diffusion and perfusion thresholds for
      infarction were established. RESULTS: Twenty-one patients were studied.
      Infarction thresholds for CBF were significantly higher in GM (median 34.6 mL/100
      g per minute, interquartile range 26.0 to 38.8) than in WM (20.8 mL/100 g per
      minute; interquartile range 18.0 to 25.9; P<0.0001). Thresholds were also
      significantly higher in GM than WM for CBV (GM: 1.67 mL/100 g; interquartile
      range 1.39 to 2.17; WM: 1.19 mL/100 g; interquartile range 0.94 to 1.53;
      P<0.0001), ADC (GM: 918x10(-6) mm2/s; 868 to 975x10(-6); WM: 805x10(-6); 747 to
      870x10(-6); P<0.001), and there was a trend toward a shorter MTT in GM (GM 4.94
      s, 4.44 to 5.38; WM 5.15, 4.11 to 5.68; P=0.11). CONCLUSIONS: GM has a higher
      infarction threshold for CBF, CBV, and ADC than WM in patients within 24 hours of
      ischemic stroke onset. Hence, when assessing patients for potential therapies,
      tissue-specific rather than whole-brain thresholds may be a more precise measure
      of predicting the likelihood of infarction.

PMID- 16574932
TI  - Respiratory muscle testing: a valuable tool for children with neuromuscular
      disorders.
AB  - RATIONALE: Data on respiratory muscle performance in children with neuromuscular
      disorders are limited. OBJECTIVES: The aim of this study was to assess
      respiratory muscle strength by volitional and nonvolitional tests and to compare
      these tests with forced vital capacity. METHODS: Inspiratory muscle strength was
      assessed by measuring transdiaphragmatic and esophageal pressures generated
      during volitional and nonvolitional maneuvers, whereas expiratory muscle strength
      was assessed by measuring the gastric pressure generated during a cough maneuver.
      Lung volumes were assessed by measuring forced vital capacity. MEASUREMENTS AND
      MAIN RESULTS: Forty-one patients with Duchenne muscular dystrophy (n = 20),
      spinal amyotrophy (n = 8), and congenital myopathy (n = 13) were included, aged 2
      to 18 yr. All the patients were able to perform the sniff and the cough maneuver.
      Sniff transdiaphragmatic pressure decreased with age in Duchenne patients,
      whereas it increased with age in patients with spinal amyotrophy and congenital
      myopathy. Magnetic stimulation of the phrenic nerves was obtained in all
      patients. Twenty-five (61%) patients were able to perform forced vital capacity.
      In the three groups of patients, a positive correlation was observed between
      volitional, assessed by the sniff maneuver, and nonvolitional respiratory muscle
      tests, assessed by the magnetic stimulation of the phrenic nerves. Also, forced
      vital capacity correlated with sniff transdiaphragmatic pressure and cough
      gastric pressure. CONCLUSIONS: Volitional respiratory muscle tests correlated
      with nonvolitional tests and with forced vital capacity. Simple volitional
      respiratory muscle tests constitute a valuable tool for the assessment of
      respiratory muscle strength in young patients with neuromuscular disorders.

PMID- 16574933
TI  - Accelerated thymic maturation and autoreactive T cells in bronchopulmonary
      dysplasia.
AB  - RATIONALE: Bronchopulmonary dysplasia (BPD), a chronic lung disease of newborns
      triggered by oxygen and barotrauma, is characterized by arrested alveolarization.
      Increased levels of bombesin-like peptides shortly after birth mediate lung
      injury: anti-bombesin antibody 2A11 protects against BPD in two baboon models.
      The role of adaptive immunity in BPD has not been explored previously.
      OBJECTIVES: Our goal was to test the hypothesis that thymic architecture and/or T
      cell function is altered with BPD, leading to autoimmunity and immunodeficiency.
      METHODS: Thymic structure was analyzed by histopathology of thymic architecture
      and immunohistochemistry for thymic maturation markers (terminal deoxynucleotidyl
      transferase, proliferating cell nuclear antigen, CD4, and CD8). Thymic cortical
      epithelial cells (nurse cells) were studied using HLA-DR and protein gene product
      9.5 as markers. Functional analysis was performed with "mixed lymphocyte
      reaction" of thymocyte or splenocyte responder cells with autologous lung cells
      as the stimulators. MEASUREMENTS AND MAIN RESULTS: 2A11 treatment attenuates
      thymic cortical involution in BPD animals, sustaining terminal deoxynucleotidyl
      transferase-positive prothymocytes and thymocyte proliferation. BPD animals have
      increased CD4(+) cells in thymic cortex and lung interstitium, which are reduced
      by 2A11. Conversely, cortical protein gene product 9.5/HLA-DR-positive thymic
      nurse cells are depleted in BPD animals, but are preserved by 2A11-treatment.
      Whereas fetal thymocytes and splenocytes respond to phythemagglutinin/ionomycin
      and to a lesser extent, to autologous lung, BPD thymocytes and splenocytes are
      phythemagglutinin/ionomycin-unresponsive, and yet react strongly to autologous
      lung. The 2A11 normalizes these responses. CONCLUSIONS: These observations
      suggest that bombesin-like peptides mediate premature thymic maturation and
      thymic nurse-cell depletion, leading to autoreactive T cells that could
      contribute to lung injury.

PMID- 16574934
TI  - Impaired alveolar macrophage response to Haemophilus antigens in chronic
      obstructive lung disease.
AB  - RATIONALE: Interactions of nontypeable Haemophilus influenzae (NTHI) with
      macrophages are implicated in the pathogenesis of chronic obstructive pulmonary
      disease (COPD). However, the immunologic mechanisms that mediate NTHI-macrophage
      inflammation are poorly understood. Outer membrane protein (OMP) P6 and
      lipooligosaccharide (LOS) of NTHI are potent immunomodulators. We theorized that
      alveolar macrophages in COPD possess fundamental immune defects that permit NTHI
      to evade host responses. OBJECTIVE: To test this hypothesis, we obtained human
      alveolar and blood macrophages from exsmokers with COPD, exsmokers without COPD,
      and nonsmokers. METHODS: Alveolar and blood macrophages from each donor were
      incubated with purified LOS and OMP P6 and with OMP P2 and the total outer
      membrane preparation (0.1-1 microg/ml). MEASUREMENTS: Supernatants (24 h) were
      assayed for IL-1beta, TNF-alpha, IL-10, IL-12, and IL-8 by multianalyte
      multiplexed flow cytometry. RESULTS: Comparative induction of COPD and non-COPD
      alveolar macrophages by LOS and OMP P6 revealed diminished IL-8, TNF-alpha, and
      IL-1beta responses of COPD alveolar macrophages (p < or = 0.03 for each). COPD
      alveolar macrophages also had diminished responses to total outer membrane (p <
      or = 0.03 for each). In contrast, COPD blood macrophages had no significant
      differences among donor groups in IL-8, TNF-alpha, or IL-1beta responsiveness to
      NTHI antigens. Diminished IL-12 responses of COPD blood macrophages to NTHI
      antigens, compared with nonsmokers, could not be independently dissociated from
      group differences in age and pack-years. CONCLUSIONS: These findings support a
      paradigm of defective immune responsiveness of alveolar macrophages, but not
      blood macrophages, in COPD.

PMID- 16574935
TI  - Defect of pro-hepatocyte growth factor activation by fibroblasts in idiopathic
      pulmonary fibrosis.
AB  - RATIONALE AND OBJECTIVES: Hepatocyte growth factor (HGF) protects against lung
      fibrosis in several animal models. Pro-HGF activation to HGF is subjected to
      regulation by its activator (HGFA), a serine protease, and HGFA-specific
      inhibitors (HAI-1 and HAI-2). Our hypothesis was that fibroblasts from patients
      with idiopathic pulmonary fibrosis (IPF) had an altered capacity to activate pro
      HGF in vitro compared with control fibroblasts. METHODS: We measured the kinetics
      of pro-HGF activation in human lung fibroblasts from control subjects and from
      patients with IPF by Western blot. HGFA, HAI-1, and HAI-2 expression was
      evaluated by immunohistochemistry, RNA protection assay, and Western blot. We
      evaluated the effect of TGF-beta(1) and PGE(2) on pro-HGF activation and HGFA,
      HAI-1, and HAI-2 expression. MAIN RESULTS: Lung fibroblasts activated pro-HGF in
      vitro. Pro-HGF activation was inhibited by serine protease inhibitors, by an anti
      HGFA antibody, as well as by HAI-1 and HAI-2. Pro-HGF activation by IPF
      fibroblasts was reduced compared with control fibroblasts. In IPF fibroblasts,
      HGFA expression was lower and HAI-1 and HAI-2 expression was higher compared with
      control fibroblasts. PGE(2) stimulated pro-HGF activation through increased
      expression of HGFA and decreased expression of its inhibitor HAI-2. In contrast,
      TGF-beta(1) reduced the ability of lung fibroblasts to activate pro-HGF through
      decreased expression of HGFA and increased expression of its inhibitors.
      CONCLUSIONS: IPF fibroblasts have a low capacity to activate pro-HGF in vitro via
      a low level of HGFA expression and high levels of HAI-1 and HAI-2 expression, and
      PGE(2) is able to partially correct this defect.

PMID- 16574936
TI  - Potent twice-weekly rifapentine-containing regimens in murine tuberculosis.
AB  - RATIONALE: Recent studies have demonstrated that intermittent administration of
      rifamycin-based regimens results in higher rates of tuberculosis relapse and
      treatment failure compared with daily therapy. Twice-weekly treatment with
      rifampin, isoniazid, and pyrazinamide may be improved by increasing Mycobacterium
      tuberculosis exposure to rifamycin by substituting rifapentine for rifampin.
      METHODS: To test this hypothesis, we compared the activities of standard daily
      and twice-weekly rifampin plus isoniazid-based regimens to those of twice-weekly
      rifapentine plus isoniazid- or moxifloxacin-containing regimens in the murine
      model of tuberculosis. Relapse rates were assessed after 4, 5, and 6 mo of
      treatment to assess stable cure. Single- and multiple-dose pharmacokinetics of
      rifampin and rifapentine were also determined. RESULTS: After 2 mo of treatment,
      twice-weekly therapy with rifapentine (15 or 20 mg/kg), moxifloxacin, and
      pyrazinamide was significantly more active than standard daily or twice-weekly
      therapy with rifampin, isoniazid, and pyrazinamide. Stable cure was achieved
      after 4 mo of twice-weekly rifapentine plus isoniazid- or moxifloxacin-containing
      therapy, but only after 6 mo of standard daily therapy. Twice-weekly rifapentine
      (15 mg/kg) displayed more favorable pharmacodynamics than did daily rifampin (10
      mg/kg). CONCLUSIONS: By virtue of the enhanced rifamycin exposure, twice-weekly
      regimens containing rifapentine (15 or 20 mg/kg) may permit shortening the
      current treatment duration by 2 mo. Such regimens warrant clinical investigation.

PMID- 16574937
TI  - Immunostimulatory sequences regulate interferon-inducible genes but not allergic
      airway responses.
AB  - RATIONALE: 1018 ISS is a synthetic oligonucleotide containing immunostimulatory
      CpG motifs. In animal studies, 1018 ISS effectively inhibited Th2-mediated lung
      inflammation, including eosinophil infiltration, and airway hyperresponsiveness.
      OBJECTIVES: To evaluate whether 1018 ISS has activity in subjects with allergic
      asthma. METHODS: Forty subjects (n = 21, 1018 ISS; n = 19, placebo) were enrolled
      in a randomized, double-blind, placebo-controlled, parallel-group study to
      examine safety, pharmacologic activity, and efficacy of 1018 ISS on allergen
      induced airway responses. Subjects received 36 mg of 1018 ISS or placebo by
      nebulization weekly for 4 wk. MEASUREMENTS: Allergen inhalation challenge was
      performed 24 h after the 2nd and 4th doses to measure the early and late fall in
      FEV(1). Sputum cells and peripheral blood mononuclear cells were collected before
      and after dosing, and gene expression was measured by quantitative polymerase
      chain reaction. MAIN RESULTS: Treatment with 1018 ISS significantly increased
      expression of interferon (IFN)-gamma and IFN-inducible genes, such as IFN-gamma
      inducible 10 kD protein (IP10), monokine induced by IFN-gamma (MIG), IFN
      stimulated gene (ISG)-54, monocyte chemotactic protein (MCP)-1, and MCP-2 from
      cells collected postdose (p < 0.05). There was no attenuation of the early or
      late decrease in FEV(1) after 1018 ISS compared with placebo, nor a reduction in
      allergen-induced sputum eosinophils or Th2-related gene expression measured in
      sputum cells. CONCLUSIONS: This study demonstrated that 1018 ISS is safe and
      pharmacologically active in the respiratory tract of asthmatics but, at this dose
      regimen, did not inhibit a fall in FEV(1) or other key features of the response
      to inhaled allergen challenge. This suggests that induction of IFN and IFN
      inducible genes alone is not sufficient to inhibit allergen-induced responses in
      asthmatic subjects.

PMID- 16574938
TI  - The effect of smoking on the transcriptional regulation of lung inflammation in
      patients with chronic obstructive pulmonary disease.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is believed to result
      from an abnormal inflammatory response in the lungs to noxious particles and
      gases usually found in cigarette smoke. OBJECTIVES: In this study, the molecular
      mechanisms for the enhanced proinflammatory cytokine gene transcription in COPD
      were investigated. METHODS: Lung tissue was examined from 56 subjects undergoing
      resection for peripheral lung tumors as follows: current smokers with (n = 14)
      and without COPD (n = 17), ex-smokers with COPD (n = 13), and nonsmokers (n =
      12). The levels of inhibitor kappaB-alpha (IkappaB-alpha), histone deacetylase 2
      (HDAC2), acetylated (ac-) histone H3 and H4, the transcription factor nuclear
      factor-kappaB (NF-kappaB), proinflammatory cytokine messenger RNA, and 8
      isoprostane were measured. MEASUREMENTS AND MAIN RESULTS: IkappaB-alpha levels
      were significantly decreased in healthy smokers and current and ex-smoking
      patients with COPD when compared with nonsmokers (p < 0.001), with an associated
      increase in NF-kappaB DNA binding in current smokers (p < 0.05). An increase in
      acetylated histone 4 (ac-H4; p < 0.01) was found in current smokers. Conversely,
      ex-smokers with COPD showed an increase in ac-H3 (p < 0.05). Decreased levels of
      cytoplasmic, but not nuclear, HDAC2 protein levels were detected. From the
      cytokine profiles, no significant differences were detected; however, interleukin
      12p40 expression correlated with ac-H4 in current smokers with COPD (p < 0.01).
      CONCLUSION: These data propose a role for modification of nucleosomal structure
      in inflammatory cytokine gene transcription in response to smoking. The imbalance
      between histone deacetylation and acetylation in favor of acetylation may
      contribute to the enhanced inflammation in smokers susceptible to the development
      of COPD.

PMID- 16574939
TI  - Erythropoiesis abnormalities contribute to early-onset anemia in patients with
      septic shock.
AB  - RATIONALE: The intimate mechanisms of early onset anemia observed in critically
      ill patients with septic shock remain unclear. OBJECTIVES: We investigated
      erythropoiesis abnormalities in this setting by studying morphologic, functional,
      and biochemical patterns of erythroid lineage. METHODS: Erythroid lineage in the
      bone marrow from patients with septic shock who developed early-onset anemia was
      compared with that of healthy control subjects. Survival and proliferation
      capacities were quantified in both groups. Biochemical and flow cytometry
      patterns of apoptosis were dissected by exploring antiapoptotic (erythropoietin
      [Epo] receptor-dependent) and proapoptotic (death receptor-dependent) pathways.
      MEASUREMENTS AND MAIN RESULTS: Erythroid lineage was morphologically similar in
      both groups. Apoptosis of glycophorin-A-positive erythroid precursors was
      increased in patients versus control subjects as assessed by labeling with
      annexin V (26.1 +/- 8.8 vs. 3.1 +/- 2.9%, p < 0.05) or 3-3'
      dihexyloxacarbocyanine iodide (55.9 +/- 10.5 vs. 19.1 +/- 5.4%, p < 0.05),
      respectively. This was associated with significant overexpression of Fas on
      erythroid precursors and higher tumor necrosis factor-alpha plasma levels in
      patients with septic shock vs. control subjects. Moreover, growth capacities of
      late erythroid progenitors of burst-forming unit erythroids (BFU-Es) at Day 10
      were impaired in the presence of serum from patients with septic shock as
      compared with the effect of serum from control subjects (27 +/- 12 vs. 109 +/- 27
      per 10(5) seeded cells, respectively; p < 0.001). Saturating concentrations of
      recombinant human Epo (rHuEpo) restored growth capacity of patients' BFU-Es (72
      +/- 14 per 10(5) seeded cells) in autologous conditions of serum. CONCLUSIONS:
      Early-onset anemia that may be observed in patients with septic shock is
      associated with defective erythropoiesis related to an excess of apoptosis that
      can be counterbalanced in vitro by rHuEpo.

PMID- 16574940
TI  - Retinoids have differing efficacies on alveolar regeneration in a dexamethasone
      treated mouse.
AB  - We have investigated the relative efficacy of a range of natural and synthetic
      retinoids on the induction of alveolar regeneration in a dexamethasone-treated
      mouse model. The aim was to explore the roles of the different retinoic acid
      receptors using receptor-selective agonists and to determine whether other
      natural retinoids in addition to all-trans-retinoic acid (tRA) were effective.
      Dexamethasone treatment of newborn pups led to a reduced lung surface area and
      increased mean chord length. Subsequently, tRA induced alveolar repair, improved
      mean chord length, and improved the lung surface area to volume ratio. We found
      that 4-oxo-RA and a retinoic acid receptor (RAR) alpha-selective compound were as
      effective as tRA at inducing alveolar regeneration, with neither showing a
      significantly better efficacy. An RARbeta-selective compound was also effective,
      whereas a RARgamma-selective compound was not. Other retinoids, such as 9-cis-RA,
      13-cis-RA, retinol, and a pan retinoid X receptor (RXR) agonist, do not induce
      significant responses. Neither did granulocyte colony-stimulating factor. We also
      showed that an RARbeta-null mutant mouse line responded to dexamethasone by
      failing to develop alveoli appropriately and that tRA induced alveolar
      regeneration, suggesting that RARbeta was not required for the regenerative
      response.

PMID- 16574941
TI  - Activation of transforming growth factor-beta by the integrin alphavbeta8 delays
      epithelial wound closure.
AB  - Transforming growth factor (TGF)-beta family members regulate multiple aspects of
      wound repair through effects on cell proliferation, matrix production, and tissue
      inflammation, but the effects of TGF-beta on wound closure itself have been
      controversial. We found that blocking antibodies to TGF-beta enhanced the degree
      of closure of scratch wounds in primary airway epithelial monolayers, while
      addition of exogenous TGF-beta1 inhibited the degree of closure, suggesting that
      endogenous activation of TGF-beta normally serves as a brake on the degree of
      wound closure. Although these cells secreted large amounts of TGF-beta2 and small
      amounts of TGF-beta1, blockade of TGF-beta1 enhanced the degree of wound closure,
      whereas blockade of TGF-beta2 had no effect. TGF-beta1 (but not TGF-beta2) can be
      activated by two members of the integrin family, alphavbeta6 and alphavbeta8,
      which are both expressed on airway epithelial cells. Wounding induced activation
      of TGF-beta through effects of both integrins, but antibodies against alphavbeta8
      enhanced the degree of wound closure, whereas antibodies against alphavbeta6 did
      not.

PMID- 16574942
TI  - Role of transient receptor potential C3 in TNF-alpha-enhanced calcium influx in
      human airway myocytes.
AB  - Previous studies have suggested that the proinflammatory cytokine, TNF-alpha,
      contributes to airway hyperresponsivness by altering airway smooth muscle (ASM)
      Ca(2+) responses to agonist stimulation. The present study examined the effects
      of TNF-alpha on Ca(2+) influx pathways in cultured human ASM cells (HASMCs).
      Proteins encoded by the transient receptor potential (TRP) gene family function
      as channels through which receptor-operated and store-operated Ca(2+) entry
      (SOCE) occur. In the present study, the presence of TRPC1, TRPC3, TRPC4, TRPC5,
      and TRPC6 mRNA and protein expression was confirmed in cultured HASMCs using RT
      PCR and Western blot analysis. TNF-alpha treatment significantly increased TRPC3
      mRNA and protein levels in HASMCs as well as SOCE. TNF-alpha treatment also
      increased both the peak and plateau intracellular Ca(2+) concentration responses
      in HASMCs elicited by acetylcholine and bradykinin. The effects of TNF-alpha
      treatment on SOCE and agonist-induced intracellular Ca(2+) concentration
      responses were attenuated using small interfering RNA transfection, which knocked
      down TRPC3 expression. Thus, in inflammatory airway diseases, TNF-alpha treatment
      may result in increased myocyte activation due to altered Ca(2+) influx pathways.
      These results suggest that TRPC3 may be an important therapeutic target in
      inflammatory airway diseases such as asthma and chronic obstructive pulmonary
      disease.

PMID- 16574943
TI  - Hydrogen peroxide induces vascular permeability via regulation of vascular
      endothelial growth factor.
AB  - Oxidative stress plays critical roles in initiation and/or worsening of
      respiratory disease process. Although reactive oxygen species (ROS) are shown to
      cause vascular leakage, the mechanisms by which ROS induce an increase in
      vascular permeability are not clearly understood. In this study, we have used a
      murine model to evaluate the effect of hydrogen peroxide (H(2)O(2)) to examine
      roles of ROS and the molecular mechanism in vascular permeability. The results
      have revealed that ROS levels, vascular endothelial growth factor (VEGF)
      expression, hypoxia-inducible factor-1alpha protein level, airway
      hyperresponsiveness, and vascular permeability are increased after inhalation of
      H(2)O(2). Administration of antioxidants markedly reduced plasma extravasation
      and VEGF levels in lungs treated with H(2)O(2). These results indicate that ROS
      may modulate vascular permeability via upregulation of VEGF expression.

PMID- 16574944
TI  - Matrix metalloproteinases promote inflammation and fibrosis in asbestos-induced
      lung injury in mice.
AB  - Inhalation of asbestos fibers causes pulmonary inflammation and eventual
      pulmonary fibrosis (asbestosis). Although the underlying molecular events are
      poorly understood, protease/antiprotease and oxidant/antioxidant imbalances are
      believed to contribute to the disease. Implicated in other forms of pulmonary
      fibrosis, the matrix metalloproteinases (MMPs) have not been examined in
      asbestosis. We therefore hypothesized that MMPs play a pathogenic role in
      asbestosis development. Wild-type C57BL/6 mice were intratracheally instilled
      with 0.1 mg crocidolite asbestos, causing an inflammatory response at 1 d and a
      developing fibrotic response at 7, 14, and 28 d. Gelatin zymography demonstrated
      an increase in MMP-9 (gelatinase B) during the inflammatory phase, while MMP-2
      (gelatinase A) was profoundly increased in the fibrotic phase.
      Immunohistochemistry revealed MMP-9 in and around bronchiolar and airspace
      neutrophils that were often associated with visible asbestos fibers. MMP-2 was
      found in fibrotic regions at 7, 14, and 28 d. No increases in RNA levels of MMP
      2, MMP-9, or MMP-8 were found, but levels of MMP-7, MMP-12, and MMP-13 RNA did
      increase at 14 d. The MMP inhibitors, TIMP-1 and TIMP-2, were also increased at 7
      28 d after asbestos exposure. To confirm the importance of MMP activity in
      disease progression, mice exposed to asbestos were given daily injections of the
      MMP inhibitor, GM6001. MMP inhibition reduced inflammation and fibrosis in
      asbestos-treated mice. Collectively, these data suggest that MMPs contribute to
      the pathogenesis of asbestosis through effects on inflammation and fibrosis
      development.

PMID- 16574945
TI  - DNA damage induced by hyperoxia: quantitation and correlation with lung injury.
AB  - Inspired oxygen, an essential therapy for cardiorespiratory disorders, has the
      potential to generate reactive oxygen species that damage cellular DNA. Although
      DNA damage is implicated in diverse pulmonary disorders, including neoplasia and
      acute lung injury, the type and magnitude of DNA lesion caused by oxygen in vivo
      is unclear. We used single-cell gel electrophoresis (SCGE) to quantitate two
      distinct forms of DNA damage, base adduction and disruption of the phosphodiester
      backbone, in the lungs of mice. Both lesions were induced by oxygen, but a marked
      difference between the two was found. With 40 h of oxygen exposure, oxidized base
      adducts increased 3- to 4-fold in the entire population of lung cells. This
      lesion displayed temporal characteristics (a progressive increase over the first
      24 h) consistent with a direct effect of reactive oxygen species attack upon DNA.
      DNA strand breaks, on the other hand, occurred in < 10% of pulmonary cells, which
      acquired severe levels of the lesion; dividing cells were preferentially
      affected. Characteristics of these cells suggested that DNA strand breakage was
      secondary to cell death, rather than a primary effect of reactive oxygen species
      attack on DNA. By analysis of IL-6- and IL-11-overexpressing transgenic animals,
      which are resistant to hyperoxia, we found that DNA strand breaks, but not base
      damage, correlated with acute lung injury. Analysis of purified alveolar type 2
      preparations from hyperoxic mice indicated that strand breaks preferentially
      affected this cell type.

PMID- 16574946
TI  - Role of macrophage migration inhibitory factor in acute lung injury in mice with
      acute pancreatitis complicated by endotoxemia.
AB  - Acute pancreatitis accompanied by a subsequent infectious attack can often lead
      to multisystem organ dysfunction, including acute lung injury (ALI), but the
      molecular mechanisms are poorly defined. In this study, we explored the role of
      the priming insult by induction of cerulein pancreatitis, which was followed by
      the second attack due to endotoxemia, in the development of ALI in mice.
      Experiments revealed that LPS injection in mice with acute pancreatitis caused
      the development of ALI, as indicated by blood-gas derangements, pulmonary
      vascular hyperpermeability, increased inflammatory cell counts in bronchoalveolar
      lavage, and histologic lung damage. This was associated with the pancreatitis
      induced increase in expression of macrophage migration inhibitory factor (MIF) in
      the lungs, together with elevated expression of Toll-like receptor (TLR)-4, both
      of which were inhibited by administration of anti-protease-activated receptor
      (PAR)-2 antibody. Furthermore, anti-MIF antibody treatment suppressed the
      pancreatitis-induced elevation of TLR-4 pulmonary expression. Genetic removal of
      MIF from mice resulted in less development of ALI in the setting of acute
      pancreatitis complicated by endotoxemia. These findings demonstrate that
      activation of protease-activated receptor-2 with trypsin, which can be released
      after pancreatitis induction, positively regulates the transcript level of MIF,
      and increased MIF results in exaggerated pulmonary expression of TLR-4, leading
      to the development of ALI with a subsequent infectious attack. We thus suggest
      that interventions designed to modulate MIF may have therapeutic advantages in
      treating ALI in patients with acute pancreatitis complicated by bacterial
      infection.

PMID- 16574947
TI  - Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis.
AB  - We previously reported that mice made deficient for the transcriptional factor
      USF2 fail to express hepcidin 1 and hepcidin 2 genes as a consequence of targeted
      disruption of the Usf2 gene lying just upstream in the locus. These mice
      developed an iron overload phenotype with excess iron deposition in parenchymal
      cells and decreased reticuloendothelial iron. At that time, although the role of
      USF2 was still confounding, we proposed for the first time the role of hepcidin
      as a negative regulator of iron absorption and iron release from macrophages.
      Accordingly, we subsequently demonstrated that hyperexpression of hepcidin 1, but
      not hepcidin 2, resulted in a profound hyposideremic anemia. To analyze the
      consequences of hepcidin 1 deletion on iron metabolism without any disturbance
      due to USF2 deficiency, we disrupted the hepcidin 1 gene by targeting almost all
      the coding region. Confirming our prior results, Hepc1(-/-) mice developed early
      and severe multivisceral iron overload, with sparing of the spleen macrophages,
      and demonstrated increased serum iron and ferritin levels as compared with their
      controls.

PMID- 16574952
TI  - Glucocorticoid-induced glucocorticoid-receptor expression and promoter usage is
      not linked to glucocorticoid resistance in childhood ALL.
AB  - Glucocorticoid (GC) resistance is an adverse prognostic factor in childhood acute
      lymphoblastic leukemia (ALL), but little is known about causes of GC resistance.
      Up-regulation of the glucocorticoid receptor (GR) has been suggested as an
      essential step to the induction of apoptosis in leukemic cells. In this study we
      investigated whether baseline mRNA expression levels of the 5 different GR
      promoter transcripts (1A1, 1A2, 1A3, 1B, and 1C) or differences in the degree of
      regulation of the GR or GR promoter transcripts upon GC exposure are related to
      GC resistance. Therefore, mRNA levels of the 5 GR promoter transcripts and of the
      GR were measured by quantitative real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR; Taqman) technology in primary ALL cells prior to and after 3,
      8, and 24 hours of prednisolone exposure. GR expression is induced upon GC
      exposure in primary ALL patient samples, which is opposite to what is found in
      tissues in which GCs do not induce apoptosis. GC resistance in childhood ALL
      cannot be attributed to an inability of resistant cells to up-regulate the
      expression of the GR upon GC exposure, nor to differences in GR promoter usage
      (at baseline and upon GC exposure).

PMID- 16574953
TI  - Variants in the ATM-BRCA2-CHEK2 axis predispose to chronic lymphocytic leukemia.
AB  - We conducted a large-scale association study to identify low-penetrance
      susceptibility alleles for chronic lymphocytic leukemia (CLL), analyzing 992
      patients and 2707 healthy controls. To increase the likelihood of identifying
      disease-causing alleles we genotyped 1467 coding nonsynonymous single nucleotide
      polymorphisms (nsSNPs) in 865 candidate cancer genes, biasing nsSNP selection
      toward those predicted to be deleterious. Preeminent associations were identified
      in SNPs mapping to genes pivotal in the DNA damage-response and cell-cycle
      pathways, including ATM F858L (odds ratio [OR] = 2.28, P < .0001) and P1054R (OR
      = 1.68, P = .0006), CHEK2 I157T (OR = 14.83, P = .0008), BRCA2 N372H (OR = 1.45,
      P = .0032), and BUB1B Q349R (OR = 1.42, P = .0038). Our findings implicate
      variants in the ATM-BRCA2-CHEK2 DNA damage-response axis with risk of CLL.

PMID- 16574954
TI  - Diagnostic application of flow cytometric characteristics of CD34+ cells in low
      grade myelodysplastic syndromes.
AB  - The diagnosis of myelodysplastic syndromes (MDS) without an increase in blasts
      and ringed sideroblasts (low-grade MDS without ringed sideroblasts [LGw/oRS]) may
      be problematic because dysplastic features are not specific to MDS and
      approximately 50% of patients with LGw/oRS lack chromosomal aberrations. Here, we
      report the usefulness of flow cytometric characteristics of CD34(+) cells for
      LGw/oRS diagnosis. Bone marrow cells from LGw/oRS patients and controls (eg,
      cytopenic individuals without MDS) were analyzed using 4-color flow cytometry
      (FCM). We objectively determined reference ranges of 13 parameters related to
      CD34(+) cells with data from controls. In LGw/oRS patients, various abnormalities
      of CD34(+) cells-eg, decrease in CD34(+) B-cell precursors, aberrant expression
      or overexpression of various antigens on CD34(+) myeloblasts-were observed. We
      constructed a reproducible, flow cytometric scoring system for LGw/oRS diagnosis.
      High scores were observed in 16 of 27 LGw/oRS patients, regardless of the
      presence or absence of chromosomal aberrations, but not in any of the 90
      controls. Among LGw/oRS patients with chromosomal aberrations, patients with
      trisomy 8 or del20(q) had low FCM scores (P = .002). As a result, most LGw/oRS
      patients were identified based on high FCM score, chromosomal aberration, or
      both.

PMID- 16574955
TI  - Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential
      regulator of immune cells using Matk/CHK-deficient mice.
AB  - Matk/CHK knockout mice were reported to show no apparent phenotypic
      abnormalities. This was thought to be due to the homologous kinase Csk that
      compensates for Matk/CHK. Here, we present the first evidence that the
      nonreceptor tyrosine kinase, Matk/CHK, is an important modulator of immune cell
      signaling. We found that the frequency of primitive hematopoietic cells, the side
      population c-kit(+) Lin(-) Sca-1(+) (SPKLS) cells, in Matk/CHK(-/-) mice was
      increased 2.2-fold compared with the control mice. Moreover, Matk/CHK deficiency
      led to significantly higher pre-B cell colony formation following IL-7
      stimulation. Interestingly, when mice received the in vivo antigen challenge of
      TNP-ovalbumin followed by restimulation, the Matk/CHK(-/-) lymph node and spleen
      cells produced significantly lower IFN-gamma levels compared with the respective
      wild-type cells. Our study indicates that Matk/CHK is not functionally redundant
      with Csk, and that this tyrosine kinase plays an important role as a regulator of
      immunologic responses.

PMID- 16574956
TI  - Unconvincing Pfizer and uncertain crucifixions.

PMID- 16574957
TI  - Miss, Mister, Doctor: how we are titled is of little consequence.

PMID- 16574958
TI  - Modernizing medical careers: a response from the Academy of Medical Royal
      Colleges.

PMID- 16574959
TI  - Changing perspectives of general medicine on general practice.

PMID- 16574960
TI  - Futures uncertain.

PMID- 16574961
TI  - Cannabis, pneumothorax and lung bullae.

PMID- 16574962
TI  - The doctor's PDA and Smartphone handbook.

PMID- 16574963
TI  - Plague, rats and the Bible again: a postscript.

PMID- 16574964
TI  - Eliot slater.

PMID- 16574966
TI  - The grand challenges of the Gates Foundation: what impact on global child health?

PMID- 16574967
TI  - Beyond consent: the potential for atrocity.

PMID- 16574968
TI  - Peer review: a flawed process at the heart of science and journals.

PMID- 16574969
TI  - The doctor's PDA and Smartphone handbook: medical records.

PMID- 16574970
TI  - Medical theories on the cause of death in crucifixion.

PMID- 16574971
TI  - Genetics of inherited retinal disease.

PMID- 16574972
TI  - A systematic review of systematic reviews of spinal manipulation.
AB  - OBJECTIVES: To systematically collate and evaluate the evidence from recent
      systematic reviews of clinical trials of spinal manipulation. DESIGN: Literature
      searches were carried out in four electronic databases for all systematic reviews
      of the effectiveness of spinal manipulation in any indication, published between
      2000 and May 2005. Reviews were defined as systematic if they included an
      explicit and repeatable inclusion and exclusion criteria for studies. RESULTS:
      Sixteen papers were included relating to the following conditions: back pain
      (n=3), neck pain (n=2), lower back pain and neck pain (n=1), headache (n=3), non
      spinal pain (n=1), primary and secondary dysmenorrhoea (n=1), infantile colic
      (n=1), asthma (n=1), allergy (n=1), cervicogenic dizziness (n=1), and any medical
      problem (n=1). The conclusions of these reviews were largely negative, except for
      back pain where spinal manipulation was considered superior to sham manipulation
      but not better than conventional treatments. CONCLUSIONS: Collectively these data
      do not demonstrate that spinal manipulation is an effective intervention for any
      condition. Given the possibility of adverse effects, this review does not suggest
      that spinal manipulation is a recommendable treatment.

PMID- 16574973
TI  - Do surgeons wish to become doctors?
AB  - OBJECTIVES: To gauge opinion among otolaryngologists about their wish to retain
      the title Mr, Miss, Ms or Mrs or to adopt the title of doctor. DESIGN: An e-mail
      questionnaire sent to all members of ENT-UK (The British Association of
      Otolaryngologists-Head and Neck Surgeons), who had registered an e-mail address
      with the ENT-UK secretariat. SETTING: The specialty group of otolaryngologists in
      the UK. PARTICIPANTS: 723 recipients of e-mails, who were members or fellows of a
      surgical Royal College and, by convention in the UK, entitled to adopt the title
      Mr, Miss, Ms or Mrs. RESULTS: 304 recipients of the e-mail questionnaire
      responded. 39% were not aware of any proposals to change the convention,
      addressing surgeons as 'doctor' in the future. Overall, 61.8% were in favour of
      retaining the current convention and retaining the title Mr or a female
      equivalent. Applying the null hypothesis that most surgeons would not like to
      change a title, the chi(2) test produced a highly significant P value of 0.0002.
      Of female respondents, however, only 43% supported retention of the current
      convention. Using Fisher's exact test to compare female and male respondents, the
      two-sided P value was highly significant at 0.006, with female respondents
      favouring the title of doctor. CONCLUSIONS: A large proportion of ENT surgeons in
      the UK responded to the questionnaire. They were unaware of proposals to change
      the current convention of address for surgeons. A significant number of those
      responding were in favour of retaining the current convention. The small
      proportion of female respondents indicated a preference for being addressed as
      'doctor'.

PMID- 16574974
TI  - Nontraumatic rhabdomyolysis: an unusual complication of diabetic hyperosmolar
      nonketotic (HONK) state.

PMID- 16574975
TI  - How easily malaria can be missed.

PMID- 16574976
TI  - Postpartum convulsions--a diagnostic enigma.

PMID- 16574977
TI  - Al-Razi and Islamic medicine in the 9th century.

PMID- 16574978
TI  - Standards of healthcare and respecting children's rights.

PMID- 16574981
TI  - Hepcidin and hemojuvelin gene expression in rat liver damage: in vivo and in
      vitro studies.
AB  - In this work, we used two rat models, partial hepatectomy (PH) and CCl(4)
      administration, to study the changes in iron pathways in response to hepatic
      damage. Liver injury induced changes in the hepatic gene expression of hepcidin,
      hemojuvelin (Hjv), several other proteins of iron metabolism, and several
      cytokines such as IL-1beta, IL-6, TNF-alpha, and IFN-gamma. Hepcidin gene
      expression was upregulated between 4 and 8 h with a maximum up to 16 h after
      surgery. However, Hjv gene expression was downregulated at the same time. An
      early upregulation of hepcidin (3 h) and downregulation of Hjv gene expression
      was found after CCl(4) administration. Transferrin receptor 1 and ferritin H gene
      expression was upregulated, whereas ferroportin 1 gene expression was
      downregulated. Hepatic IL-6 gene expression was upregulated early after PH and
      reached maximum 8 h after the PH. In CCl(4)-induced liver injury, IL-6, IL-1beta,
      TNF-alpha, and IFN-gamma upregulation were found at the maximum 12 h after the
      administration of the toxin. Treatment of isolated rat hepatocytes with IL-6 and,
      to a lesser extent, with IL-1beta but not with TNF-alpha or IFN-gamma dose
      dependently upregulated hepcidin and downregulated Hjv gene expression. In
      hepatic damage, changes of the hepatic gene expression of the main proteins
      involved in iron metabolism may be induced by locally synthesized mediators.

PMID- 16574982
TI  - Ethanol sensitizes NF-kappaB activation in pancreatic acinar cells through
      effects on protein kinase C-epsilon.
AB  - Although ethanol abuse is the most common cause of pancreatitis, the mechanism of
      alcohol's effect on the pancreas is not well understood. Previously, we
      demonstrated that in vitro ethanol treatment of pancreatic acinar cells augmented
      the CCK-8-induced activation of NF-kappaB, a key signaling system involved in the
      inflammatory response of pancreatitis. In the present study, we determine the
      role for individual PKC isoforms in the sensitizing effect of ethanol on NF
      kappaB activation. Dispersed rat pancreatic acini were treated with and without
      ethanol and then stimulated with CCK-8; 100 nM CCK-8 caused both NF-kappaB and
      PKC-delta, -epsilon, and -zeta activation, whereas 0.1 nM CCK-8 did not increase
      PKC-epsilon, PKC-zeta, or NF-kappaB activity. CCK-8 (0.1 nM) did activate PKC
      delta. PKC-epsilon activator alone did not cause NF-kappaB activation; however,
      together with 0.1 nM CCK-8, it caused NF-kappaB activation. Ethanol activated PKC
      epsilon without affecting other PKC isoforms or NF-kappaB activity. Of note,
      stimulation of acini with ethanol and 0.1 nM CCK-8 resulted in the activation of
      PKC-delta, PKC-epsilon, and NF-kappaB. The NF-kappaB activation to 0.1 nM CCK-8
      in ethanol-pretreated acini was inhibited by both PKC-delta inhibitor and PKC
      epsilon inhibitor. Taken together, these results demonstrate the different modes
      of activation of PKC isoforms and NF-kappaB in acini stimulated with ethanol,
      high-dose CCK-8, and low-dose CCK-8, and furthermore suggest that activation of
      both PKC-epsilon and -delta is required for NF-kappaB activation. These results
      suggest that ethanol enhances the CCK-8-induced NF-kappaB activation at least in
      part through its effects on PKC-epsilon.

PMID- 16574983
TI  - Targeted disruption of the murine CCK1 receptor gene reduces intestinal lipid
      induced feedback inhibition of gastric function.
AB  - Cholecystokinin (CCK), acting at CCK1 receptors (CCK1Rs) on intestinal vagal
      afferent terminals, has been implicated in the control of gastrointestinal
      function and food intake. Using CCK1R(-/-) mice, we tested the hypothesis that
      lipid-induced activation of the vagal afferent pathway and intestinal feedback of
      gastric function is CCK1R dependent. In anesthetized CCK1R(+/+) ("wild type")
      mice, meal-stimulated gastric acid secretion was inhibited by intestinal lipid
      infusion; this was abolished in CCK1R(-/-) mice. Gastric emptying of whole egg,
      measured by nuclear scintigraphy in awake mice, was significantly faster in
      CCK1R(-/-) than CCK1R(+/+) mice. Gastric emptying of chow was significantly
      slowed in response to administration of CCK-8 (22 pmol) in CCK1R(+/+) but not
      CCK1R(-/-) mice. Activation of the vagal afferent pathway was measured by
      immunohistochemical localization of Fos protein in the nucleus of the solitary
      tract (NTS; a region where vagal afferents terminate). CCK-8 (22 pmol ip)
      increased neuronal Fos expression in the NTS of fasted CCK1R(+/+) mice; CCK
      induced Fos expression was reduced by 97% in CCK1R(-/-) compared with CCK1R(+/+)
      mice. Intralipid (0.2 ml of 20% Intralipid and 0.04 g lipid), but not saline,
      gavage increased Fos expression in the NTS of fasted CCK1R(+/+) mice; lipid
      induced Fos expression was decreased by 47% in CCK1R(-/-) compared with
      CCK1R(+/+)mice. We conclude that intestinal lipid activates the vagal afferent
      pathway, decreases gastric acid secretion, and delays gastric emptying via a
      CCK1R-dependent mechanism. Thus, despite a relatively normal phenotype,
      intestinal feedback in response to lipid is severely impaired in these mice.

PMID- 16574984
TI  - Tumor necrosis factor inhibits growth hormone-mediated gene expression in
      hepatocytes.
AB  - Growth hormone (GH) stimulates STAT5 phosphorylation by JAK2, which activates IGF
      I and serine protease inhibitor 2.1 (Spi 2.1) transcription, whereas STAT5
      dephosphorylation by protein tyrosine phosphatases (PTPs) terminates this signal.
      We hypothesized that the inhibitory effects of TNF on GH signaling and gene
      transcription were responsible for hepatic GH resistance. CWSV-1 hepatocytes were
      treated with TNF, pervanadate (a PTP inhibitor), or both, before GH stimulation.
      Total and tyrosine-phosphorylated JAK2, STAT5, ERK1/2, SHP-1 and SHP-2, IGF-I,
      and Spi 2.1 mRNA levels were measured. GH stimulated STAT5 and ERK1/2
      phosphorylation, IGF-I, and Spi 2.1 mRNA expression. TNF attenuated JAK2/STAT5
      and ERK1/2 phosphorylation and IGF-I and Spi 2.1 mRNA expression following GH
      stimulation. SHP-1 and SHP-2 protein levels were unaltered by TNF or GH, and the
      GH-induced increase in SHP-1 PTP activity was not further increased by TNF. In
      TNF-treated cells, pervanadate restored STAT5 and ERK1/2 phosphorylation to
      control levels following GH stimulation but did not restore IGF-I or Spi 2.1 mRNA
      induction. Cells transfected with a Spi 2.1 promoter-luciferase vector
      demonstrate a 50-fold induction in luciferase activity following GH stimulation
      or cotransfection with a constitutively active STAT5 vector. TNF prevented the
      induction of Spi 2.1 promoter activity by GH and the STAT5 construct. We conclude
      that TNF does not inhibit GH activity by inducing SHP-1 or -2 expression and that
      correction of GH signaling defects in TNF-treated cells by pervanadate does not
      restore GH-induced gene expression. The inhibitory effects of TNF on GH-mediated
      gene transcription appear independent of STAT5 activity and previously identified
      abnormalities in JAK2/STAT5 signaling.

PMID- 16574985
TI  - Administration of r-VEGF-A prevents hepatic artery ligation-induced bile duct
      damage in bile duct ligated rats.
AB  - The hepatic artery, through the peribiliary plexus, nourishes the intrahepatic
      biliary tree. During obstructive cholestasis, the nutritional demands of
      intrahepatic bile ducts are increased as a consequence of enhanced proliferation;
      in fact, the peribiliary plexus (PBP) displays adaptive expansion. The effects of
      hepatic artery ligation (HAL) on cholangiocyte functions during cholestasis are
      unknown, although ischemic lesions of the biliary tree complicate the course of
      transplanted livers and are encountered in cholangiopathies. We evaluated the
      effects of HAL on cholangiocyte functions in experimental cholestasis induced by
      bile duct ligation (BDL). By using BDL and BDL + HAL rats or BDL + HAL rats
      treated with recombinant-vascular endothelial growth factor-A (r-VEGF-A) for 1
      wk, we evaluated liver morphology, the degree of portal inflammation and
      periductular fibrosis, microcirculation, cholangiocyte apoptosis, proliferation,
      and secretion. Microcirculation was evaluated using a scanning electron
      microscopy vascular corrosion cast technique. HAL induced in BDL rats 1) the
      disappearance of the PBP, 2) increased apoptosis and impaired cholangiocyte
      proliferation and secretin-stimulated ductal secretion, and 3) decreased
      cholangiocyte VEGF secretion. The effects of HAL on the PBP and cholangiocyte
      functions were prevented by r-VEGF-A, which, by maintaining the integrity of the
      PBP and cholangiocyte proliferation, prevents damage of bile ducts following
      ischemic injury.

PMID- 16574986
TI  - FTY720 suppresses CD4+CD44highCD62L- effector memory T cell-mediated colitis.
AB  - FTY720, a sphingosine-derived immunomodulator, causes immunosuppression via
      enhancement of lymphocyte sequestration into secondary lymphoid organs, thereby
      preventing their antigen-activated T cell egress to sites of inflammation. FTY720
      is highly effective in inhibiting autoimmunity in various animal models. However,
      there is little known about how FTY720 controls the migration property of memory
      T cells. Here, we demonstrated that FTY720 prevents the development of colitis
      induced by the adoptive transfer of lamina propria (LP) colitogenic effector
      memory CD4+ T cells (TEM cells; CD45RB(low)CD44(high)CD62L-) into severe combined
      immunodeficiency (SCID) mice and suppresses interferon-gamma, interleukin-2, and
      tumor necrosis factor-alpha production by LP CD4+ T cells. The numbers of spleen,
      peripheral blood, mesenteric lymph node, and LP CD4+ T cells in FTY720-treated
      mice were significantly reduced compared with those in control mice. Notably, LP
      CD4+ TEM cells as well as splenic CD4+CD45RBhigh T cells expressed several
      spingosine-1-phosphate receptors that are targets for FTY720. Furthermore, FTY720
      also prevented the development of colitis induced by the adoptive transfer of
      splenic CD4+CD45RBhigh T cells into SCID mice. Collectively, the present data
      indicate that FTY720 treatment may offer the potential not only to prevent the
      onset of disease but also to treat memory T cell-mediated autoimmune diseases
      including inflammatory bowel diseases.

PMID- 16574987
TI  - Early activation of endoplasmic reticulum stress is associated with arginine
      induced acute pancreatitis.
AB  - Endoplasmic reticulum (ER) stress mechanisms have been found to play critical
      roles in a number of diseases states, such as diabetes mellitus and Alzheimer
      disease, but whether they are involved in acute pancreatitis is unknown. Here we
      show for the first time that all major ER stress sensing and signaling mechanisms
      are present in exocrine acini and are activated early in the arginine model of
      experimental acute pancreatitis. Pancreatitis was induced in rats by
      intraperitoneal injection of 4.0 g/kg body wt arginine. Pancreatitis severity was
      assessed by analysis of serum amylase, pancreatic trypsin activity, water
      content, and histology. ER stress-related molecules PERK, eIF2alpha, ATF6, XBP-1,
      BiP, CHOP, and caspase-12 were analyzed. Arginine treatment induced rapid and
      severe pancreatitis, as indicated by increased serum amylase, pancreatic tissue
      edema, and acinar cell damage within 4 h. Arginine treatment also caused an early
      activation of ER stress, as indicated by phosphorylation of PERK and its
      downstream target eIF2alpha, ATF6 translocation into the nucleus (within 1 h),
      and upregulation of BiP (within 4 h). XBP-1 splicing and CHOP expression were
      observed within 8 h. After 24 h, increased activation of the ER stress-related
      proapoptotic molecule caspase-12 was observed along with an increase in caspase-3
      activity and TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end
      labeling (TUNEL) staining in exocrine acini. These results indicate that ER
      stress is an important early acinar cell event that likely contributes to the
      development of acute pancreatitis in the arginine model.

PMID- 16574988
TI  - Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by
      oil of mustard and by dextran sulfate sodium.
AB  - Oil of mustard (OM) is a potent neuronal activator that is known to elicit
      visceral hyperalgesia when given intracolonically, but the full extent to which
      OM is also proinflammatory in the gastrointestinal tract is not known. We have
      previously shown that male CD-1 mice given a single administration of 0.5% OM
      develop a severe colitis that is maximum at day 3 and that gradually lessens
      until essentially absent by day 14. OM-induced neuronal stimulation is reported
      to be reduced by cannabinoid agonists, and cannabinoid receptor 1 (CB1R)-/- mice
      have exacerbated experimental colitis. Therefore, we examined the role of
      cannabinoids in this OM-induced 3-day model of colitis in CD-1 mice and in a 7
      day dextran sulfate sodium (DSS) colitis model in BALB/c mice. In OM colitis, the
      CB1R-selective agonist ACEA and the CB2R-selective agonist JWH-133 reduced (P <
      0.05) colon weight gain (means +/- SE; 82 +/- 13% and 47 +/- 15% inhibition,
      respectively), colon shrinkage (98 +/- 24% and 42 +/- 12%, respectively), colon
      inflammatory damage score (49 +/- 11% and 40 +/- 12%, respectively), and diarrhea
      (58 +/- 12% and 43 +/- 11%, respectively). Histological damage was similarly
      reduced by these treatments. Likewise, CBR agonists attenuated DSS colitis,
      albeit at higher doses; ACEA at 10 mg/kg, twice daily, inhibited (P < 0.05)
      macroscopic and microscopic scores (46 +/- 9% and 63 +/- 7%, respectively);
      whereas 20 mg/kg, twice daily, of JWH-133 was required to diminish (P < 0.05)
      macroscopic and microscopic scores (29 +/- 7% and 43 +/- 5%, respectively). CB1R
      and CB2R immunostaining of colon sections revealed that CB1R in enteric neurons
      was more intense in colitic vs. control mice; however, CB1R was also increased in
      the endothelial layer in OM colitis only. CB2R immunostaining was more marked in
      infiltrated immune cells in OM colitis. These findings validate the OM colitis
      model with respect to the DSS model and provide strong support to the emerging
      idea that cannabinoid receptor activation mediates protective mechanisms in
      experimental colitis. The demonstration of CB1R agonist effects in colitis
      support the neurogenic nature of the OM-induced colitis model and reinforce the
      importance of neuronal activation in intestinal inflammation.

PMID- 16574989
TI  - Apoptotic pathway in the rat small intestinal mucosa is different between fasting
      and ischemia-reperfusion.
AB  - We have previously demonstrated that fasting and ischemia-reperfusion (I/R)
      induced apoptosis in rat intestinal mucosa. It is widely accepted that apoptosis
      is induced through two main pathways. This study aimed to compare apoptotic
      pathways following fasting and I/R. Rats were divided into two groups: the I/R
      group involved occlusion of the superior mesenteric artery for 60 min, followed
      by 60-min reperfusion, whereas the fasting group involved fasting for 24 or 48 h.
      Intestinal apoptosis was assessed as percentage of fragmented DNA, by
      electrophoresis and by a terminal deoxynucleotidyl transferase mediated dUDP
      biotin nick- end labeling (TUNEL) assay. Apoptotic proteins including death
      ligands/receptors and caspases were evaluated by Western blot analysis. Small
      intestinal mucosal height and mitochondrial dehydrogenase function were assessed.
      Fasting and I/R significantly induced intestinal apoptosis. Mucosal height was
      significantly decreased in fasting rats, and mitochondrial dysfunction was
      induced only by I/R. Expressions of Fas, Fas ligand, and TNF-alpha type 1
      receptor were enhanced in fasting and I/R rats. After I/R, expressions of
      cytochrome c and cleaved caspase-9 were significantly increased. In contrast,
      expressions of cleaved caspase-8 and cleaved caspase-3 increased in fasting rats.
      Fasting promoted mucosal apoptosis via a receptor-mediated type I apoptotic
      pathway in the rat small intestine, and I/R induced apoptosis via a mitochondria
      mediated type II pathway.

PMID- 16574990
TI  - Androstenediol administration after trauma-hemorrhage attenuates inflammatory
      response, reduces organ damage, and improves survival following sepsis.
AB  - Although androstenediol (adiol or 5-androstene-3beta,17beta-diol), a metabolite
      of dehydroepiandrosterone (DHEA), has protective effects following trauma
      hemorrhage (T-H), it remains unknown whether administration of adiol has any
      salutary effects on the inflammatory response and outcome following a combined
      insult of T-H and sepsis. Male rats underwent T-H shock [mean arterial pressure
      (MAP) 40 mmHg for 90 min] followed by resuscitation. Adiol (1 mg/kg body wt) or
      vehicle was administered at the end of resuscitation. Sepsis was induced by cecal
      ligation and puncture (CLP) at 20 h after T-H or sham operation. Five hours after
      CLP, plasma and tissue samples were analyzed for cytokines (IL-6 and IL-10), MPO,
      neutrophil chemotactic factor (CINC-3), and liver injury (alanine
      aminotransferase and lactate dehydrogenase). In another group of rats, the
      gangrenous cecum was removed at 10 h after CLP, the cavity was irrigated with
      warm saline and closed in layers, and mortality was recorded over 10 days. T-H
      followed by CLP produced a significant elevation in plasma IL-6 and IL-10 levels,
      enhanced neutrophil cell activation, and resulted in liver injury. Adiol
      administration prevented the increase in cytokine production, neutrophil cell
      activation, and attenuated liver injury. Moreover, rats subjected to the combined
      insult, receiving vehicle or adiol, had a 50% and 6% mortality, respectively.
      Since adiol administration suppresses proinflammatory cytokines, reduces liver
      damage, and decreases mortality after the combined insult of T-H and sepsis, this
      agent appears to be a novel adjunct to fluid resuscitation for decreasing T-H
      induced septic complications and mortality.

PMID- 16574991
TI  - Prostaglandin-mediated inhibition of Na+/H+ exchanger isoform 2 stimulates
      recovery of barrier function in ischemia-injured intestine.
AB  - Prostaglandins stimulate repair of the ischemia-injured intestinal barrier in the
      porcine ileum through a mechanism involving cAMP-dependent Cl- secretion and
      inhibition of electroneutral Na+/H+ exchanger (NHE) activity. In the present
      study, we focused on the role of individual NHE isoforms in the recovery of
      barrier function. Ischemia-injured porcine ileal mucosa was mounted on Ussing
      chambers. Short-circuit current (I(sc)), transepithelial electrical resistance
      (TER), and isotopic fluxes of 22Na were measured in response to PGE2 and
      selective inhibitors of epithelial NHE isoforms. Immunoassays were used to assess
      the expression of NHE isoforms. Forty-five minutes of intestinal ischemia
      resulted in a 45% reduction in TER (P < 0.01). Near-complete restitution occurred
      within 60 min. Inhibition of NHE2 with HOE-694 (25 microM) added to the mucosal
      surface of the injured ileum stimulated significant elevations in TER,
      independent of changes in I(sc) and histological evidence of restitution.
      Pharmacological inhibition of NHE3 or NHE1 with mucosal S-3226 (20 microM) or
      serosal cariporide (25 microM), respectively, had no effect. Ischemia-injured
      tissues treated with mucosal S-3226 or HOE-694 exhibited equivalent reductions in
      mucosal-to-serosal fluxes of 22Na+ (by approximately 35%) compared with
      nontreated ischemia-injured control tissues (P < 0.05). Intestinal ischemia
      resulted in increased expression of the cytoplasmic NHE regulatory factor EBP50
      in NHE2 but not in NHE3 immunoprecipitates. Selective inhibition of NHE2, and not
      NHE3, induces recovery of barrier function in the ischemia-injured intestine.

PMID- 16574992
TI  - Chronic PKC-beta2 activation in HT-29 Cl.19a colonocytes prevents cAMP-mediated
      ion secretion by inhibiting apical membrane CFTR targeting.
AB  - We investigated the effects of chronically applied PKC-stimulating phorbol esters
      on subcellular CFTR expression and localization in polarized HT-29 Cl.19A
      monolayers. Modulation of PKC activity with the PKC-beta-specific agonist 12
      deoxyphorbol 13-phenylacetate 20-acetate (DOPPA) or nonisoform-selective PMA
      altered monolayer CFTR immunofluorescence. A decrease in the CFTR signal within
      the luminal cellular pole was noted with both phorbol esters. Volumetric analysis
      of the intracellular CFTR signal revealed that both compounds promoted CFTR
      accumulation into punctate vesicle-like structures found adjacent to the cellular
      tight junction [labeled with zona occludens (ZO)-1 antibody], extending basally
      (DOPPA) into the cell. Puncta were more frequent with DOPPA and larger in size
      with PMA. DOPPA also promoted ZO-1 accumulation at tricellular corners associated
      with enhanced CFTR puncta number. The observed loss of CFTR immunofluorescence
      signal induced by low-dose PMA was related to CFTR sequestration into fewer
      cytoplasmic puncta and correlated with larger increases in PKC substrate
      phosphorylation. Both phorbol esters downregulated steady-state cellular CFTR
      mRNA levels by 70%. However, the effects of DOPPA and PMA were largely
      independent of CFTR biosynthesis: expression levels were 80-85% of control, and
      the glycosylation status of immunoprecipitated protein remained largely
      unchanged. Thus changes in cellular CFTR localization correlated with our
      companion study showing that PMA-induced inhibition of transcellular cAMP
      dependent short-circuit current (ISC) was accompanied by cytoplasmic PKC-beta2
      accumulation and modest activation of PKC-beta1 and PKC-epsilon. The inhibitory
      effect of DOPPA on ISC was related solely to increased cytoplasmic PKC-beta2
      levels. Thus PKC-beta2 is hypothesized to participate in the regulation of CFTR
      apical plasma membrane targeting within the constitutive cellular biosynthetic
      pathway.

PMID- 16574993
TI  - Chronic PKC-beta activation in HT-29 Cl.19a colonocytes prevents cAMP-mediated
      ion secretion by inhibiting apical membrane current generation.
AB  - We investigated the effects of PKC-stimulating 12-deoxyphorbol 13-phenylacetate
      20-acetate (DOPPA) and phorbol 12-myristate 13-acetate (PMA) phorbol esters on
      cAMP-dependent, forskolin (FSK)-stimulated, short-circuit Cl- current (ISC-cAMP)
      generation by colonocyte monolayers. These agonists elicited different actions
      depending on their dose and incubation time; PMA effects at the onset (<5 min)
      were independent of cAMP agonist and were characterized by transient anion
      dependent transcellular and apical membrane ISC generation. DOPPA failed to
      elicit similar responses. Whereas chronic (24 h) exposure to both agents
      inhibited FSK-stimulated transcellular and apical membrane ISC-cAMP, the effects
      of DOPPA were more complex: this conventional PKC-beta-specific agonist also
      stimulated Ba2+-sensitive basolateral membrane-dependent facilitation of
      transcellular ISC-cAMP. PMA did not elicit a similar phenomenon. Prolonged
      exposure to high-dose PMA but not DOPPA led to apical membrane ISC-cAMP recovery.
      Changes in PKC alpha-, beta1-, gamma-, and epsilon-isoform membrane partitioning
      and expression correlated with these findings. PMA-induced transcellular ISC
      correlated with PKC-alpha membrane association, whereas low doses of both agents
      inhibited transcellular and apical membrane ISC-cAMP, increased PKC-beta1,
      decreased PKC-beta2 membrane association, and caused reciprocal changes in
      isoform mass. During the apical membrane ISC-cAMP recovery after prolonged high
      dose PMA exposure, an almost-complete depletion of cellular PKC-beta1 and a
      significant reduction in PKC-epsilon mass occurred. Thus activated PKC-beta1
      and/or PKC-epsilon prevented, whereas activated PKC-alpha facilitated, apical
      membrane ISC-cAMP. PKC-beta-dependent augmentation of transcellular ISC-cAMP at
      the level of the basolateral membrane demonstrated that transport events with
      geographically distinct subcellular membranes can be independently regulated by
      the PKC beta-isoform.

PMID- 16574994
TI  - Mechanisms and pathophysiological implications of sinusoidal endothelial cell gap
      formation following treatment with galactosamine/endotoxin in mice.
AB  - Neutrophil extravasation from sinusoids is a critical step for acute inflammatory
      tissue injury. However, the role of sinusoidal endothelial cells (SECs) in this
      process remains unclear. Matrix metalloproteinases (MMPs) have been shown to
      involve gap formation in SECs in several liver diseases. Therefore, the present
      study examined SEC modifications elicited by galactosamine (Gal)/endotoxin (ET).
      Treatment of male C3Heb/FeJ mice with Gal/ET or Gal/TNF caused the formation of
      numerous gaps in SECs at 4 h when no neutrophil extravasation occurred. Six hours
      after Gal/ET or Gal/TNF treatment, blood elements started to penetrate to the
      extrasinusoidal space through large gaps. Treatment with ET alone caused
      sinusoidal neutrophil accumulation but no gap formation, neutrophil
      extravasation, or hemorrhage. Gal/ET treatment increased hepatic MMP-2 and MMP-9
      mRNA expression (6.7- and 11-fold, respectively). Pretreatment with 2-[(4
      biphenylsulfonyl) amino]-3-phenyl-propionic acid, an MMP-2/MMP-9 inhibitor (5
      mg/kg), minimized gap formation after Gal/ET and Gal/TNF treatment. The MMP
      inhibitor reduced injury only in the Gal/ET model mainly due to reduced TNF
      formation. The MMP inhibitor attenuated sinusoidal neutrophil accumulation at 6 h
      but failed to attenuate Gal/TNF-induced liver injury at 7 h due to excessive
      apoptosis. These results suggest that Gal/ET or Gal/TNF activates MMPs, which are
      responsible for SEC gap formation. Although the initial appearance of gap
      formation is independent of neutrophils, the gaps allow initial contact of
      neutrophils with damaged hepatocytes. In addition, MMP activation promotes
      neutrophil accumulation in sinusoids.

PMID- 16574995
TI  - Suppressor of cytokine signaling-2 limits intestinal growth and enterotrophic
      actions of IGF-I in vivo.
AB  - Suppressors of cytokine signaling (SOCS) typically limit cytokine receptor
      signaling via the JAK-STAT pathway. Considerable evidence demonstrates that SOCS2
      limits growth hormone (GH) action on body and organ growth. Biochemical evidence
      that SOCS2 binds to the IGF-I receptor (IGF-IR) supports the novel possibility
      that SOCS2 limits IGF-I action. The current study tested the hypothesis that
      SOCS2 normally limits basal or IGF-I-induced intestinal growth and limits IGF-IR
      signaling in intestinal epithelial cells. Intestinal growth was assessed in mice
      homozygous for SOCS2 gene deletion (SOCS2 null) and wild-type (WT) littermates at
      different ages and in response to infused IGF-I or vehicle or EGF and vehicle.
      The effects of SOCS2 on IGF-IR signaling were examined in ex vivo cultures of
      SOCS2 null and WT intestine and Caco-2 cells. Compared with WT, SOCS2 null mice
      showed significantly enhanced small intestine and colon growth, mucosal mass, and
      crypt cell proliferation and decreases in radiation-induced crypt apoptosis in
      jejunum. SOCS2 null mice showed significantly greater growth responses to IGF-I
      in small intestine and colon. IGF-I-stimulated activation of IGF-IR and
      downstream signaling intermediates were enhanced in the intestine of SOCS2 null
      mice and were decreased by SOCS2 overexpression in Caco-2 cells. SOCS2 bound
      directly to the endogenous IGF-IR in Caco-2 cells. The intestine of SOCS2 null
      mice also showed enhanced growth responses to infused EGF. We conclude that SOCS2
      normally limits basal and IGF-I- and EGF-induced intestinal growth in vivo and
      has novel inhibitory effects on the IGF-IR tyrosine kinase pathway in intestinal
      epithelial cells.

PMID- 16574996
TI  - Promise of new vascular-disrupting agents balanced with cardiac toxicity: is it
      time for oncologists to get to know their cardiologists?

PMID- 16574997
TI  - Developing a new framework for dose calculation.

PMID- 16574998
TI  - Phase I clinical evaluation of weekly administration of the novel vascular
      targeting agent, ZD6126, in patients with solid tumors.
AB  - PURPOSE: ZD6126 is a novel vascular-targeting agent that induces selective
      effects on the morphology of endothelial cells by disrupting the tubulin
      cytoskeleton. This leads to cell detachment and tumor vessel congestion,
      resulting in extensive central necrosis in a range of tumor xenograft models.
      Results from a phase I dose-escalation study of ZD6126 are reported. PATIENTS AND
      METHODS: Thirty-two patients with advanced cancer received weekly ZD6126 infusion
      (5 to 28 mg/m2). Assessments for safety and pharmacokinetics were performed.
      Circulating endothelial cells (CECs) were quantified as a pharmacodynamic marker
      of vascular damage. RESULTS: Maximum concentrations of the active species were
      observed 5 to 25 minutes from the start of infusion, and decayed in a
      biexponential manner with a half-life of 1 to 3 hours. Maximum serum
      concentration and area under the time-concentration curve increased with dose in
      a linear fashion across the dose range of 5 to 28 mg/m2. One patient treated at
      10 mg/m2 with a history of ischemic heart disease experienced acute myocardial
      infarction 2 weeks after drug discontinuation. Four others had asymptomatic
      creatine phosphokinase-muscle-brain elevation. Maximum-tolerated dose (MTD) was
      reached at 20 mg/m2/wk. Dose-limiting toxicities at 28 mg/m2 were hypoxia caused
      by pulmonary embolism and an asymptomatic decrease in left ventricular ejection
      fraction. No objective antitumor responses were observed. CEC levels increased in
      the hours after infusion, indicating potential effect of the compound on the
      vasculature. CONCLUSION ZD6126 administered as a weekly infusion was clinically
      well tolerated. The MTD was reached at 20 mg/m2.

PMID- 16574999
TI  - Evaluation of an alternate dosing strategy for cisplatin in patients with extreme
      body surface area values.
AB  - PURPOSE: The majority of cytotoxic drugs for adults are dosed based on body
      surface area (BSA), aiming to reduce interpatient variability in drug exposure.
      We prospectively studied the usefulness of BSA-based dosing of cisplatin in
      patients at extremes of BSA values. PATIENTS AND METHODS: Patients were randomly
      assigned to receive a fixed dose of cisplatin in course 1, and a BSA-adjusted
      dose in course 2, or vice versa. The fixed dose was based on the average BSA for
      males and females, while extremes were set at BSA values exceeding the average +/
      1 standard deviation. Subsequently, we retrospectively analyzed data from a
      normal population. RESULTS: In 25 patients assessable for both courses, the use
      of a fixed dose of cisplatin resulted in reduced exposure to unbound platinum in
      patients at the upper extremes of BSA (P = .003) and higher exposures in patients
      at the lower extremes (P = .009), as compared with exposures following the BSA
      adjusted dose. Although clearance was related to BSA (R2 = 0.44; P < .001), only
      a small reduction in interpatient variability in clearance after correction for
      BSA was achieved (20.8% v 17.1%). In the retrospective analysis, compared with
      the average patient, the clearance of unbound platinum in patients with a BSA
      value < or = 1.65 m2 was 16% slower (P < .001), while an 18% faster clearance (P
      < .001) was observed in patients with a BSA value > or = 2.05 m2. CONCLUSION
      Unless better predictors for platinum clearance are identified, fixed-dose
      regimens per BSA cluster (< or = 1.65 m2; 1.66 m2 to 2.04 m2; > or = 2.05 m2) are
      recommended.

PMID- 16575000
TI  - High WT1 expression after induction therapy predicts high risk of relapse and
      death in pediatric acute myeloid leukemia.
AB  - PURPOSE: To determine whether minimal residual disease (MRD) measured by Wilms'
      tumor gene 1 (WT1) expression is a prognostic marker in pediatric acute myeloid
      leukemia (AML), we quantified WT1 transcript by real-time quantitative-polymerase
      chain reaction in 92 AML at diagnosis and during follow-up. PATIENTS AND METHODS:
      Patients (median age, 6 years; cytogenetics, favorable 27%, intermediate 59%,
      poor 13%) were treated between 1995 and 2002 and enrolled in Leucemie aigue
      Myeloblastique Enfant (LAME) 89/91, LAME 99 pilot study and Acute Promyelocytic
      Leukemia French collaborative protocols. With a median follow-up of 26 months,
      event-free survival was 56% with a standard deviation (SD) of 5% and overall
      survival of 62.5% with an SD of 6%. WT1 copy number was normalized by TATA box
      binding protein gene transcripts and expressed as WT1/TBP x 1,000 ratio. Median
      WT1 ratio in normal patient controls was 12 (range, 0 to 57). A level over two SD
      than normal bone marrow controls (ie, WT1 ratio > 50), was considered as
      significant overexpression. RESULTS: At diagnosis, WT1 overexpression was
      detected in 78% of patients (72 of 92 patients; median copy ratio, 2231). The WT1
      values were significantly higher (P = .01) in favorable cytogenetics and lower (P
      < .0001) in M5-FAB subtype, 11q23 rearrangements (P < .001), and infants (P =
      .003) and demonstrate a strong correlation with fusion transcript AML1-ETO, PML
      RARalpha expression. After induction treatment, WT1 ratio was analyzed in 46 of
      72 patients and found above 50 in nine of 36 patients and five of 25 patients at
      D35-50 and 3 to 5 months, respectively. WT1 ratio > 50 after induction is an
      independent prognostic risk factor of relapse (P = .002) and death (P = .02).
      CONCLUSION: WT1 quantification is an informative molecular marker for MRD in
      pediatric AML and is now performed as prospective analysis in ELAM02 protocol.

PMID- 16575001
TI  - White race as a risk factor for hypothyroidism after treatment for pediatric
      Hodgkin's lymphoma.
AB  - PURPOSE: Hypothyroidism frequently occurs after treatment for pediatric Hodgkin's
      lymphoma, but race has not been investigated as a risk factor for this delayed
      toxicity. The aim of this study was to determine whether race is an independent
      risk factor for hypothyroidism in survivors of pediatric Hodgkin's lymphoma.
      PATIENTS AND METHODS: To identify differences between black and white patients in
      the development of hypothyroidism after treatment for Hodgkin's lymphoma, we
      conducted a retrospective study of consecutively treated pediatric patients with
      newly diagnosed Hodgkin's lymphoma treated at St Jude Children's Research
      Hospital (Memphis, TN) from January 1980 through December 2002. Clinical or
      biochemical hypothyroidism was defined by an above normal thyroxine-stimulating
      hormone concentration or by the need for thyroid hormone replacement therapy.
      RESULTS: The 461 patients (388 white patients, 73 black patients) where followed
      for a median of 11.3 years (range, 1.8 to 24.9 years). Hypothyroidism developed
      in 196 (43%) of 461 patients after a median of 2.9 years (range, 0.7 to 11.3
      years) after diagnosis of Hodgkin's lymphoma. Hypothyroidism developed in 47% of
      white patients but in only 21% of black patients (hazard ratio = 2.7; 95% CI, 1.6
      to 4.6). After adjusting for other risk factors for hypothyroidism (thyroid
      radiation dose, sex, and nodular sclerosis histology), the risk of hypothyroidism
      in white patients was 2.5 times (95% CI, 1.5 to 4.3 times) the risk in black
      patients (P < .001). CONCLUSION: White patients have a higher risk of
      hypothyroidism after neck irradiation for pediatric Hodgkin's lymphoma than black
      patients.

PMID- 16575002
TI  - Human telomere reverse transcriptase expression predicts progression and survival
      in pediatric intracranial ependymoma.
AB  - PURPOSE: Pediatric intracranial ependymomas are a heterogeneous group of
      neoplasms with unpredictable clinical and biologic behavior. As part of ongoing
      studies to identify potential biologic and therapeutic markers, we analyzed the
      role of human telomere reverse transcriptase (hTERT; the catalytic subunit of
      telomerase) expression as a prognostic marker for this disease. PATIENTS AND
      METHODS: Primary intracranial ependymomas that were resected at our institution
      between 1986 and 2004 were identified through the pathology and oncology
      databases. A tissue array was constructed from the patient samples and hTERT
      expression was evaluated by immunohistochemistry. Twenty-one samples were also
      analyzed for telomerase activity (telomerase repeat amplification protocol
      assay). RESULTS: Eighty-seven tumors from 65 patients were analyzed. Five-year
      progression-free survival was 57% (SEM, 12%) and 21% (SEM, 8%) for hTERT-negative
      and hTERT-positive tumors, respectively (P = .002). Five-year overall survival
      was 84% (SEM, 7%) and 41% (SEM, 7%) for hTERT-negative and hTERT-positive tumors,
      respectively (P = .001). There was good correlation between telomerase activity
      and hTERT expression (kappa = 0.637). Multivariate analysis revealed hTERT
      expression to be the single most important predictor of survival of all known
      pathologic, clinical, and treatment factors (hazard ratio, 60.4; 95% CI, 6.4 to
      561). All four patients with hTERT-negative tumors at relapse are still alive,
      with median follow-up of 11.2 years. CONCLUSION: In this study, hTERT expression
      was the strongest predictor of outcome and was independent of other clinical and
      pathologic prognostic markers. It represents a simple and reliable biologic
      prognostic factor for intracranial ependymomas. These results should be confirmed
      in larger prospective trials.

PMID- 16575003
TI  - Translocation carcinomas of the kidney after chemotherapy in childhood.
AB  - PURPOSE: Children who survive cancer are at more than 19-fold increased risk of
      developing another malignancy. Renal cell carcinoma (RCC) occurring as a
      secondary malignancy is uncommon. Translocation RCC, bearing TFE3 or TFEB gene
      fusions, are recently recognized entities for which risk factors have not been
      identified. PATIENTS AND METHODS: We describe the clinical, pathologic,
      cytogenetic, and molecular data on six translocation RCCs that arose in five
      young patients who had received chemotherapy. RESULTS: The ages at time of
      diagnosis of the RCC ranged from 6 to 22 years. Histologically, these tumors
      showed typical features previously described for translocation RCCs. At the
      molecular level, three tumors contained the ASPL-TFE3 fusion, two contained Alpha
      TFEB, and one contained PRCC-TFE3. The intervals between chemotherapy and the
      diagnosis of RCC ranged from 4 to 13 years. The indications for the antecedent
      chemotherapy were varied and included acute promyelocytic leukemia, acute myeloid
      leukemia with t(9;11), bilateral Wilms' tumor, systemic lupus erythematosus, and
      conditioning regimen of bone marrow transplant for Hurler's syndrome. Only the
      latter patient had also received radiation. Hence, among 39 genetically confirmed
      translocation RCCs in our personal experience, six (15%) have arisen in patients
      who had received cytotoxic chemotherapy. CONCLUSION: Cytotoxic chemotherapy may
      predispose to the development of renal translocation carcinomas.

PMID- 16575004
TI  - Skip metastases in osteosarcoma: experience of the Cooperative Osteosarcoma Study
      Group.
AB  - PURPOSE: The outlook for patients with osteosarcoma who present with synchronous
      regional bone metastases (skip metastases), either in the primary bone site or
      transarticular, is considered to be extremely poor. This study was conducted to
      further investigate the prognostic implication of skip metastases in
      osteosarcoma. PATIENTS AND METHODS: The authors retrospectively analyzed the
      collected data of 1,765 consecutive patients with newly diagnosed high-grade
      osteosarcoma of bone who were registered in the neoadjuvant Cooperative
      Osteosarcoma Study Group studies and identified 24 patients (1.4%) with
      unequivocally proven skip metastases. All 24 patients were treated by an
      aggressive surgical approach coupled with polychemotherapy. Demographic,
      diagnostic, tumor, and treatment-related variables and response and survival data
      were analyzed. RESULTS: Skip metastases were identified preoperatively in 11 of
      24 patients by bone scan, eight of 22 patients by plain x-ray, 15 of 18 patients
      by magnetic resonance imaging, and five of 10 patients by computed tomography. A
      complete surgical remission (CSR) of all clinically detectable tumor sites was
      achieved in 22 of 24 patients during front-line therapy. With a median follow-up
      time of 4.4 years (8 years for survivors) from diagnosis, 12 patients were alive,
      all of whom were in continuous CSR. Survival did correlate with location of skip
      metastases and histologic response to neoadjuvant chemotherapy. CONCLUSION:
      Synchronous regional bone metastases are rare in osteosarcoma, and preoperative
      detection relies on appropriate diagnostic imaging. Aggressive multimodal therapy
      holds the promise to achieve prolonged survival, especially in patients in whom
      these metastases occur within the same bone as the primary lesion and whose
      tumors respond well to chemotherapy.

PMID- 16575005
TI  - Treatment complications in children diagnosed with neuroblastoma during a
      screening program.
AB  - PURPOSE: The Quebec Neuroblastoma Screening Program was put in place to
      investigate the possibility of decreasing mortality from high-risk neuroblastoma
      through early screening. We assess treatment complications in the patients
      diagnosed during this screening program. PATIENTS AND METHODS: A total of 476,603
      patients born during the screening period were eligible. Parents of 425,838
      children (89%) agreed to participate in the 3-week screening, and 73% agreed to
      participate in the 6-month screening. Forty-five patients had neuroblastoma. We
      reviewed the medical and research charts for all patients diagnosed by screening.
      Follow-up was available from 8 to 13 years after screening. RESULTS: Forty-five
      patients were diagnosed by screening. All patients were treated according to the
      Pediatric Oncology Group recommendations of the time. All patients had surgery,
      and 29 patients received chemotherapy. No patient died from neuroblastoma. Eleven
      patients suffered complications from treatment. Two patients had life-threatening
      complications. CONCLUSION: In view of the lack of impact of screening programs on
      neuroblastoma mortality, evidence that many of the tumors detected through
      screening can be observed without treatment and the serious complications that
      may arise from therapy, we do not support neuroblastoma screening programs for
      children.

PMID- 16575006
TI  - Association of high-level MRP1 expression with poor clinical outcome in a large
      prospective study of primary neuroblastoma.
AB  - PURPOSE: We have previously shown in a retrospective study that expression of the
      multidrug transporter gene MRP1 (ABCC1) is associated with outcome in
      neuroblastoma. We have now undertaken a prospective analysis to examine the
      independent prognostic significance of MRP1 expression in a large cohort of
      primary untreated neuroblastomas. PATIENTS AND METHODS: Two hundred nine
      diagnostic neuroblastoma samples from patients prospectively enrolled onto the
      Pediatric Oncology Group biology protocol 9047 were analyzed for expression of
      the MRP1, MDR1, MYCN, and TRKA genes using real-time polymerase chain reaction.
      Expression levels were correlated with established prognostic indicators and
      disease outcome. RESULTS: MRP1 expression was detected in all tumors analyzed,
      and levels were significantly higher in tumors with versus without MYCN
      amplification (P < .0001). High levels of MRP1 were highly predictive of both
      event-free survival (EFS; P < .001) and overall survival (OS; P < .001). High
      level MYCN and low-level TRKA were also predictive of poor outcome. MDR1
      expression demonstrated no prognostic significance. After adjustment for the
      effect of statistically significant prognostic indicators in multivariate models,
      MRP1 expression retained significant prognostic value for both EFS (hazard ratio
      = 3.0; P = .0011) and OS (hazard ratio = 2.5; P = .0095), whereas MYCN
      amplification did not have prognostic significance. CONCLUSION: The results of
      this prospective study confirm our earlier findings and support a clinically
      relevant role for MRP1 gene expression in neuroblastoma. These findings have
      implications for the biology, prognosis, and treatment of this disease and
      provide evidence that MRP1 is a bone fide molecular target for reversing
      chemotherapy resistance in aggressive drug-refractory neuroblastoma.

PMID- 16575007
TI  - Role of radiotherapy in supratentorial primitive neuroectodermal tumor in young
      children: results of the German HIT-SKK87 and HIT-SKK92 trials.
AB  - PURPOSE: To assess the outcome of young children with supratentorial primitive
      neuroectodermal tumor (stPNET) treated by intensive postoperative chemotherapy
      alone compared with treatment with chemotherapy and delayed radiotherapy (RT).
      PATIENTS AND METHODS: From 1987 to 1992, children younger than 3 years of age
      with stPNET were enrolled in the HIT-SKK87 trial in Germany and Austria. After
      surgery, low-risk patients received maintenance chemotherapy before RT. In high
      risk patients, intensive induction chemotherapy was followed by maintenance
      chemotherapy until delayed RT was initiated. In the following trial, HIT-SKK92
      methotrexate-based chemotherapy was applied. In children with complete remission
      after three cycles, therapy was finished without irradiation. Otherwise,
      radiotherapy or salvage chemotherapy was administered. RESULTS: Twenty-nine
      children were eligible (age, 3.0 to 37.0 months). All children received
      chemotherapy. In 15 children, no RT was administered. Four children had tumor
      progression during chemotherapy and underwent irradiation. In 10 patients, RT was
      given after chemotherapy. Overall survival (OS) and progression-free survival
      (PFS) rates after 3 years were 17.2% and 14.9%, respectively. Twenty-four
      children relapsed (13 at the tumor site only, three at distant site, and eight at
      both local and distant sites). Positive impact on survival was observed in
      children with complete resection but without statistical significance.
      Administration of RT was the only significant predictive factor for OS and PFS.
      Only one child not having RT survived. CONCLUSION: Outcome of infants and babies
      with stPNET is unsatisfactory. Omission of RT jeopardizes survival, even if
      intensive chemotherapy is applied. We suggest to limit any delay of RT to a
      maximum of 6 months even in young children.

PMID- 16575008
TI  - Phase I to II study of pleurectomy/decortication and intraoperative intracavitary
      hyperthermic cisplatin lavage for mesothelioma.
AB  - PURPOSE: To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and
      outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients
      undergoing pleurectomy for malignant pleural mesothelioma (MPM). PATIENTS AND
      METHODS: Sixty-one patients were prospectively registered. Forty-four resectable
      patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the
      resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and
      250 mg/m2) at 42 degrees C and then intravenous sodium thiosulfate (16 g/m2 over
      6 hours). Survival estimates were compared using the log-rank test and
      proportional hazards regression. RESULTS: Median age was 71 years (range, 50 to
      82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or
      mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose
      limiting renal toxicity occurred at 250 mg/m2, establishing the MTD at 225 mg/m2.
      Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep
      venous thrombosis (four of 44 patients, 9%). Median survival time of all
      registered patients was 9 months, and the median survival time of resected
      patients was 13 months. Survival estimates differed significantly for resectable
      patients exposed to low doses (50 to 150 mg/m2; n = 9; median, 6 months) versus
      high doses (175 to 250 mg/m2; n = 35; median, 18 months) of hyperthermic
      cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v
      9 months, respectively; P < .0001). Low dose level (relative risk = 3.418) and
      nonepithelial histology (relative risk = 2.336) were independent risk factors for
      poor survival. Twenty patients with epithelial tumors who underwent high-dose
      cisplatin lavage had a 26-month median survival time. CONCLUSION: Pleurectomy and
      high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible
      in this patient population with restricted surgical options. An apparent dose
      related survival benefit warrants further study.

PMID- 16575009
TI  - Improvement of overall and failure-free survival in stage IV follicular lymphoma:
      25 years of treatment experience at The University of Texas M.D. Anderson Cancer
      Center.
AB  - PURPOSE: Advanced-stage follicular lymphoma is considered incurable. The pace of
      improvements in treatment has been slow. This article analyzes five sequential
      cohorts of patients with stage IV follicular lymphoma treated between 1972 and
      2002. METHODS: Five consecutive studies (two were randomized trials) involving
      580 patients were analyzed for overall survival (OS), failure-free survival
      (FFS), and survival after first relapse. A proportional hazards analysis, and
      subset analyses using the follicular lymphoma international prognostic index
      (FLIPI) score were performed. Treatment regimens included: cyclophosphamide,
      doxorubicin, vincristine, prednisone, bleomycin (CHOP-Bleo); CHOP-Bleo followed
      by interferon alfa (IFN-alpha); a rotation of three regimens (alternating triple
      therapy), followed by IFN-alpha; fludarabine, mitoxantrone, dexamethasone (FND)
      followed by IFN-alpha; and FND plus delayed versus concurrent rituximab followed
      by IFN-alpha. RESULTS: Improvements in 5-year OS (from 64% to 95%) and FFS (from
      29% to 60%) indicate steady progress, perhaps partly due to more effective
      salvage therapies, but the FFS data also indicate improved front-line therapies;
      these observations held true after controlling for differences in prognostic
      factors among the cohorts. The FLIPI model adds rigor to and facilitates
      comparisons among the different cohorts. An unexpected finding in this study was
      a trend toward an apparent FFS plateau. CONCLUSION: Evolving therapy, including
      the incorporation of biologic agents, has led to stepwise significant outcome
      improvements for patients with advanced-stage follicular lymphoma. The apparent
      plateau in the FFS curve, starting approximately 8 to 10 years from the beginning
      of treatment, raises the issue of the potential curability of these patients.

PMID- 16575010
TI  - Phase III intergroup study of fludarabine phosphate compared with
      cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed
      patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma.
AB  - PURPOSE: To compare the efficacy and safety of fludarabine phosphate with
      cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated,
      advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase
      III, multicenter study. PATIENTS AND METHODS: Between 1993 and 1997, patients
      were randomly assigned to treatment with either fludarabine (25 mg/m2
      intravenously [IV] daily for 5 days every 4 weeks) or CVP (cyclophosphamide 750
      mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 1; and prednisone, 40 mg/m2
      orally on days 1 through 5 every 4 weeks). Results Overall response (OR) rates
      were significantly improved in the fludarabine arm versus the CVP arm, both for
      the intent-to-treat (ITT) population and assessable patients (P < .001). Complete
      response (CR) rates in the ITT population were also higher after fludarabine
      treatment. The CR rate was 38.6% for fludarabine compared with 15.0% for CVP.
      There were no statistically significant differences in time to progression (TTP),
      time to treatment failure (TTF), and overall survival (OS) between treatment
      groups. WHO grades 3 and 4 hematologic adverse events were more common in the
      fludarabine arm. However, concerning the higher incidence of granulocytopenia,
      this did not translate to more infections in fludarabine-treated patients.
      CONCLUSION: Newly diagnosed lgNHL patients who received fludarabine achieved
      higher OR and CR rates compared with CVP-treated patients. No differences in TTP,
      TTF, and OS were noted. Fludarabine is a highly active single agent in lgNHL.
      Combination therapies incorporating fludarabine are now being further evaluated
      as first-line therapy in follicular NHL.

PMID- 16575011
TI  - Tumor thymidylate synthase 1494del6 genotype as a prognostic factor in colorectal
      cancer patients receiving fluorouracil-based adjuvant treatment.
AB  - PURPOSE: The purpose of this study was to analyze the value of germline and tumor
      thymidylate synthase (TS) genotyping as a prognostic marker in a series of
      colorectal cancer patients receiving adjuvant fluorouracil (FU) -based treatment.
      PATIENTS AND METHODS: One hundred twenty-nine colorectal cancer patients
      homogeneously treated with FU plus levamisole or leucovorin in the adjuvant
      setting were included. TS enhancer region, 3R G > C single nucleotide
      polymorphism (SNP), and TS 1494del6 polymorphisms were assessed in both fresh
      frozen normal mucosa and tumor. Mutational analyses of TS and allelic imbalances
      were studied in all primary tumors and in 18 additional metachronic metastases.
      TS protein immunostaining was assessed in an expanded series of 214 tumors.
      Multivariate Cox models were adjusted for stage, differentiation, and location.
      RESULTS: Tumor genotyping (frequency of allelic loss, 26%) showed that the 3R/3R
      genotype was associated with a better outcome (hazard ratio [HR] = 0.38; 95% CI,
      0.16 to 0.93; P = .020 for the recessive model). 3R G > C SNP genotyping did not
      add prognostic information. Tumor TS 1494del6 allele (frequency of allelic loss,
      36%) was protective (for each allele with the deletion, based on an additive
      model, HR = 0.42; 95% CI, 0.22 to 0.82; P = .0034). Both polymorphisms were in
      strong linkage disequilibrium (D' = 0.71, P < .001), and the 3R/-6 base pair (bp)
      haplotype showed a significant overall survival benefit compared with the most
      prevalent haplotype 2R/+6bp (HR = 0.42; 95% CI, 0.20 to 0.85; P = .017). No TS
      point mutation was detected in primary tumors or metastases. TS protein
      immunostaining was not associated with survival or any of the genotypes analyzed.
      CONCLUSION: Tumor TS 1494del6 genotype may be a prognostic factor in FU-based
      adjuvant treatment of colorectal cancer patients.

PMID- 16575012
TI  - Predictive factors for outcome in a phase II study of gefitinib in second-line
      treatment of advanced esophageal cancer patients.
AB  - PURPOSE: The efficacy of the epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitor (TKI) gefitinib was assessed in a phase II study in patients
      with advanced esophageal cancer. Several biologic features were investigated as
      potential markers of gefitinib activity. PATIENTS AND METHODS: Patients with
      advanced esophageal cancer, who had failed one line of prior chemotherapy, were
      administered gefitinib 500 mg/d. Response was evaluated every 8 weeks. Tumor
      material obtained before gefitinib treatment was investigated for gene mutations
      in EGFR, k-ras, and PIK3CA; protein expression levels of EGFR, p-Akt, and p-Erk;
      and EGFR gene amplification. RESULTS: Of the 36 enrolled patients, one (2.8%)
      achieved a partial response, 10 (27.8%) had stable disease, 17 (47.2%)
      experienced progression on treatment, and eight (22.2%) were not assessable for
      response. The progression-free survival time was 59 days, and the median overall
      survival time was 164 days. Although EGFR or PIK3CA mutations were absent, k-ras
      mutations were found in two patients with progressive disease. High EGFR gene
      copy number was identified in two patients experiencing partial response or
      progressive disease. A higher disease control rate (response plus stable disease)
      was observed in females (P = .038) and in patients with squamous cell carcinoma
      (SCC; P = .013) or high EGFR expression (P = .002). CONCLUSION: Gefitinib has a
      modest activity in second-line treatment of advanced esophageal cancer. However,
      the patient outcome was significantly better in female patients and in patients
      demonstrating high EGFR expression or SCC histology. The selection of esophageal
      cancer patients for future studies with EGFR-TKIs based on the level of EGFR
      expression in their tumors or SCC histology should be considered.

PMID- 16575013
TI  - Randomized trial of peer counseling on reproductive health in African American
      breast cancer survivors.
AB  - PURPOSE: We designed a peer counseling program to improve sexual function,
      increase knowledge about reproductive health, and decrease menopausal symptoms
      and infertility-related distress for African American breast cancer survivors.
      PATIENTS AND METHODS: Women were randomly assigned to immediate counseling or a 3
      month waitlist. Three peer counselors conducted a 3-session intervention using a
      detailed workbook. Questionnaires at baseline, after the waitlist period, at
      posttreatment, and at 3-month follow-up assessed spirituality, sexual function,
      menopause symptoms, emotional distress, relationship satisfaction, fertility
      concerns, and knowledge about reproductive health and breast cancer. At the
      postcounseling assessment, women rated the workbook, their counselor, and the
      program. RESULTS: Of 93 women screened, 60 women (65%) enrolled in the study.
      Women who completed counseling (80%; N = 48) had a mean age of 49 years (standard
      deviation [SD], 8 years) and a mean follow-up of 4.5 years (SD, 3.8 years) since
      cancer diagnosis. Almost all rated the workbook as very easy to understand (94%)
      and their counselor as very knowledgeable (96%) and very skillful (98%). Eighty
      one percent rated the program as "very useful to me." Immediate counseling and
      waitlist groups did not differ at baseline in psychologic adjustment, nor did
      scores change during the waitlist period. Therefore, the groups were combined in
      analyzing outcomes. Knowledge of reproductive issues improved significantly from
      baseline to 3-month follow-up (P < .0001), as did emotional distress (P = .0047)
      and menopause symptoms (P = .0128). Sexually dysfunctional women became less
      distressed (P = .0167). CONCLUSION: Women valued the Sisters Peer Intervention in
      Reproductive Issues After Treatment program highly and found it relevant. The
      program had positive effects on knowledge and target symptoms.

PMID- 16575014
TI  - Survival prediction in patients with glioblastoma multiforme by human telomerase
      genetic variation.
AB  - PURPOSE: Glioblastoma multiforme (GBM) is the most common and aggressive glioma
      with the poorest survival. Use of biomarkers for screening patients with GBM may
      be used to modify treatments and improve outcomes. The level of human telomerase
      (hTERT) expression is an independent predictor of outcome of many cancers, and a
      functional variant of hTERT MNS16A (shorter tandem repeats or short [S] allele)
      is associated with increased hTERT mRNA expression. We investigated whether hTERT
      MNS16A variant genotype predicted survival in GBM patients. PATIENTS AND METHODS:
      We genotyped hTERT MNS16A in 299 GBM patients using polymerase chain reaction and
      determined hTERT genotype by classifying the DNA band of 243 or 272 base pairs
      (bp) as S allele and 302 or 333 bp as long (L) allele. We compared overall
      survival using Kaplan-Meier estimates and equality of survival distributions
      using the log-rank test, and we computed univariate and multivariate Cox
      proportional hazards models to estimate the effects of selected variables.
      RESULTS: Overall survival differed significantly by hTERT MNS16A genotype, with
      median survivals of 25.1, 14.7, and 14.6 months for the SS, SL, and LL genotypes,
      respectively. Compared with the SS genotype, the hazard ratios for the SL and LL
      genotypes were 1.69 and 1.87, respectively, after adjustment for other factors.
      Multivariate Cox regression analysis showed an independent statistically
      significant association between the hTERT MNS16A variant genotype and outcome.
      CONCLUSION: A functional hTERT MNS16A genotype is a potential biomarker for
      assessment of survival outcome of GBM. Larger studies are needed to verify these
      findings.

PMID- 16575015
TI  - Peripheral neuropathy induced by microtubule-stabilizing agents.
AB  - Microtubule-stabilizing agents (MTSAs), including the taxanes and epothilones,
      are effective chemotherapeutic agents for the treatment of many cancers.
      Neuropathy is a major adverse effect of MTSA-based chemotherapy, with severe
      peripheral neuropathy (grade 3 or 4) occurring in as many as 30% of patients
      treated with a MTSA. MTSA-induced neuropathy usually resolves gradually after
      cessation of the treatment. The most reliable method to accurately assess MTSA
      induced neuropathy is by clinical evaluation, although additional techniques are
      being developed and evaluated. Among MTSA-induced neuropathy, the most
      extensively studied is that induced by taxanes; such a neuropathy usually
      presents as sensory neuropathy and is more common with paclitaxel than docetaxel.
      The incidence of MTSA-induced neuropathy seems to depend on the MTSA dose per
      treatment cycle, the schedule of treatment, and the duration of the infusion.
      Although there have been several small clinical trials with neuroprotective
      agents, early recognition and supportive care are the best approaches for
      prevention and management of MTSA-induced neuropathy. In the future, research
      should focus on elucidating the mechanism of MTSA-induced neuropathy, developing
      reliable in vivo and in vitro preclinical models to study MTSA-induced
      neuropathy, developing a more reliable grading system for MTSA-induced
      neuropathy, developing more reliable methods for evaluating MTSA-induced
      neuropathy, and evaluating the efficacy of potential neuroprotective agents in
      clinical trials.

PMID- 16575016
TI  - Deliberate deceit of family members: a challenge to providers of clinical
      genetics services.

PMID- 16575017
TI  - Chronic eosinophilic leukemia/hypereosinophilic syndrome and acute leukemia.

PMID- 16575018
TI  - Acute effects of thixotropy conditioning of inspiratory muscles on end-expiratory
      chest wall and lung volumes in normal humans.
AB  - Thixotropy conditioning of inspiratory muscles consisting of maximal inspiratory
      effort performed at an inflated lung volume is followed by an increase in end
      expiratory position of the rib cage in normal human subjects. When performed at a
      deflated lung volume, conditioning is followed by a reduction in end-expiratory
      position. The present study was performed to determine whether changes in end
      expiratory chest wall and lung volumes occur after thixotropy conditioning. We
      first examined the acute effects of conditioning on chest wall volume during
      subsequent five-breath cycles using respiratory inductive plethysmography (n =
      8). End-expiratory chest wall volume increased after conditioning at an inflated
      lung volume (P < 0.05), which was attained mainly by rib cage movements.
      Conditioning at a deflated lung volume was followed by reductions in end
      expiratory chest wall volume, which was explained by rib cage and abdominal
      volume changes (P < 0.05). End-expiratory esophageal pressure decreased and
      increased after conditioning at inflated and deflated lung volumes, respectively
      (n = 3). These changes in end-expiratory volumes and esophageal pressure were
      greatest for the first breath after conditioning. We also found that an increase
      in spirometrically determined inspiratory capacity (n = 13) was maintained for 3
      min after conditioning at a deflated lung volume, and a decrease for 1 min after
      conditioning at an inflated lung volume. Helium-dilution end-expiratory lung
      volume increased and decreased after conditioning at inflated and deflated lung
      volumes, respectively (both P < 0.05; n = 11). These results suggest that
      thixotropy conditioning changes end-expiratory volume of the chest wall and lung
      in normal human subjects.

PMID- 16575019
TI  - Increases in lung expansion alter pulmonary hemodynamics in fetal sheep.
AB  - Prolonged increases in fetal lung expansion stimulate fetal lung growth and
      development, but the effects on pulmonary hemodynamics are unknown. Our aim was
      to determine the effect of increased fetal lung expansion, induced by tracheal
      obstruction (TO), on pulmonary blood flow (PBF) and vascular resistance (PVR).
      Chronically catheterized fetal sheep (n = 6) underwent TO from 120 to 127 days of
      gestational age (term approximately 147 days); tracheas were not obstructed in
      control fetuses (n = 6). PBF, PVR, and changes to the PBF waveform were
      determined. TO significantly increased lung wet weight compared with control
      (166.3 +/- 20.2 vs. 102.0 +/- 18.8 g; P < 0.05). Despite the increase in
      intraluminal pressure caused by TO (5.0 +/- 0.9 vs. 2.4 +/- 1.0 mmHg; P < 0.001),
      PBF and PVR were similar between groups after 7 days (TO 28.1 +/- 3.2 vs. control
      34.1 +/- 10.0 ml.min(-1).100 g lung wt(-1)). However, TO markedly altered
      pulmonary hemodynamics associated with accentuated fetal breathing movements,
      causing a reduction rather than an increase in PBF at 7 days of TO. To account
      for the increase in intraluminal pressure, the pressure was equalized by draining
      the lungs of liquid on day 7 of TO. Pressure equalization increased PBF from 36.8
      +/- 5.2 to 112.4 +/- 22.8 ml/min (P = 0.01) and markedly altered the PBF
      waveform. These studies provide further evidence to indicate that intraluminal
      pressure is an important determinant of PBF and PVR in the fetus. We suggest that
      the increase in PBF associated with pressure equalization following TO reflects
      an increase in growth of the pulmonary vascular bed, leading to an increase in
      its cross-sectional area.

PMID- 16575020
TI  - Effects of changes in central blood volume on carotid-vasomotor baroreflex
      sensitivity at rest and during exercise.
AB  - The purpose of this investigation was to examine whether the effect of changes in
      central blood volume on carotid-vasomotor baroreflex sensitivity at rest was the
      same during exercise. Eight men (means +/- SE: age 26 +/- 1 yr; height 180 +/- 3
      cm; weight 86 +/- 6 kg) participated in the present study. Sixteen Torr of lower
      body negative pressure (LBNP) were applied to decrease central venous pressure
      (CVP) at rest and during steady-state leg cycling at 50% peak O2 uptake (104 +/-
      20 W). Subsequently, infusions of 25% human serum albumin solution were
      administered to increase CVP at rest and during exercise. During all protocols,
      heart rate, arterial blood pressure, and CVP were recorded continuously. At each
      stage of LBNP or albumin infusion, the maximal gain (G(max)) of the carotid
      vasomotor baroreflex function curve was measured using the neck pressure and neck
      suction technique. LBNP reduced CVP and increased the G(max) of the carotid
      vasomotor baroreflex function curve at rest (+63 +/- 25%, P = 0.006) and during
      exercise (+69 +/- 19%, P = 0.002). In contrast to the LBNP, increases in CVP
      resulted in the G(max) of the carotid-vasomotor baroreflex function curve being
      decreased at rest -8 +/- 4% and during exercise -18 +/- 5% (P > 0.05). These
      findings indicate that the relationship between CVP and carotid-vasomotor
      baroreflex sensitivity was nonlinear at rest and during exercise and suggests a
      saturation load of the cardiopulmonary baroreceptors at which carotid-vasomotor
      baroreflex sensitivity remains unchanged.

PMID- 16575022
TI  - Effects of darbepoetin injections on erythrocyte membrane transport protein
      expressions in humans.
AB  - The present study investigated the effects of injected darbepoetin [novel
      erythropoietin stimulating protein (NESP)] on the density of three erythrocyte
      membrane transport proteins: the lactate-H+ cotransporter (monocarboxylate
      transporter 1), the chloride/bicarbonate exchanger 1 (anion exchanger 1), and the
      water channel aquaporin 1. Thirteen subjects were injected with NESP once a week
      for 4 wk. Blood samples were obtained before, during, and after the injection
      period, and the erythrocyte transport proteins were determined by Western
      blotting. The NESP injections induced a transient increase in hematocrit, red
      cell volume, and reticulocyte fraction. The density of aquaporin 1 protein was
      higher (maximal increase +59%) (P < 0.01) during the injection period compared
      with the preinjection value and lower (P < 0.01) after the injection period. The
      density of anion exchanger 1 protein was higher (maximal increase +15%) (P <
      0.05) during the injection period compared with the preinjection value and tended
      (P = 0.06) to be lower after the injection period than before the injection
      period. The density of the erythrocyte monocarboxylate transporter 1 protein was
      higher (maximal increase +43%) (P < 0.05) during the injection period than in the
      preinjection period. Age separation experiments using self-creating Percoll
      gradients demonstrated a higher density of membrane transport proteins in young
      red blood cells. These data suggest that the NESP-induced increase in membrane
      transport proteins is caused by a higher fraction of newly formed erythrocytes
      (and reticulocytes), which have a higher density of membrane transport proteins.
      However, increased incorporation of membrane proteins during erythrocyte
      formation may also be involved. We suggest that NESP improves the quality of
      erythrocyte membrane transport through these mechanisms.

PMID- 16575021
TI  - Ovine bronchial-derived relaxing factor: changes with development and hyperoxic
      ventilation.
AB  - Recent studies suggest that a bronchial-derived relaxing factor (BrDRF) decreases
      the contractility of newborn, but not fetal, rat pulmonary arteries (PAs) by a
      nitric oxide (NO)-mediated mechanism. We studied the effect of an adjacent
      bronchus on PA contractility to norepinephrine (NE) in late-gestation fetal (n =
      7), neonatal (1 day old, n = 9), ventilated neonatal (24-h ventilation from birth
      with 100% oxygen, n = 9), and adult sheep (n = 6) in the presence and absence of
      the NO synthase inhibitor N(omega)-nitro-l-arginine (l-NNA). The sheep were
      anesthetized and killed, and fifth-generation PA rings with and without an
      attached adjacent bronchus (PA+Br) were contracted in standard tissue baths with
      NE (10(-8)-10(-6) M). NE contractions were expressed as fraction of KCl (118 mM)
      contraction and as grams of contraction force. NE contractions were significantly
      diminished by the presence of an attached bronchus in the neonatal and ventilated
      neonatal and adult, but not fetal, lambs. Hyperoxic ventilation markedly
      increased NE contractions in PA and PA+Br. l-NNA significantly enhanced NE
      contractions in PA+Br in postnatal but not in fetal lambs. Pretreatment with l
      NNA abolished the difference between NE contractions in PA and PA+Br in neonatal
      but not in hyperoxic ventilated neonatal lambs. We conclude that there is a BrDRF
      that is developmentally regulated and has vascular activity postnatally but not
      during fetal life. The effect of BrDRF is predominantly mediated by NO in air
      breathing neonatal lambs but may involve a second non-NO mediator following
      hyperoxic ventilation. We speculate that BrDRF may have an important role in
      postnatal changes in pulmonary arterial reactivity.

PMID- 16575023
TI  - Load-independent index of diastolic filling: model-based derivation with in vivo
      validation in control and diastolic dysfunction subjects.
AB  - Maximum elastance is an experimentally validated, load-independent systolic
      function index stemming from the time-varying elastance paradigm that decoupled
      extrinsic load from (intrinsic) contractility. Although Doppler echocardiography
      is the preferred method of diastolic function (DF) assessment, all echo-derived
      indexes are load dependent, and no invasive or noninvasive load-independent index
      of filling (LIIF) exists. In this study, we derived and experimentally validated
      a LIIF. We used a kinematic filling paradigm (the parameterized diastolic filling
      formalism) to predict and derive the (dimensionless) dynamic diastolic efficiency
      M, defined by the slope of the peak driving force [maximum driving force (kx(o))
      proportional, variant peak atrioventricular (AV) gradient] to maximum
      viscoelastic resistive force [peak resistive force (cE(peak))] relation. To
      validate load independence, we analyzed E-waves recorded while load was varied
      via tilt table (head up, horizontal, and head down) in 16 healthy volunteers. For
      the group, linear regression of E-wave derived kx(o) vs. cE(peak) yielded kx(o) =
      M (cE(peak)) + B, r2 = 0.98; where M = 1.27 +/- 0.09 and B = 5.69 +/- 1.70.
      Effects of diastolic dysfunction (DD) on M were assessed by analysis of
      preexisting simultaneous cath-echo data in six DD vs. five control subjects.
      Average M for the DD group (M = 0.98 +/- 0.07) was significantly lower than
      controls (M = 1.17 +/- 0.05, P < 0.001). We conclude that M is a LIIF because it
      uncouples intrinsic DF (i.e., the pressure-flow relation) from extrinsic load
      (left ventricular end-diastolic pressure). Larger M values imply better DF in
      that increasing AV pressure gradient results in relatively smaller increases in
      peak resistive losses (cE(peak)). Conversely, lower M implies that increasing AV
      gradient leads to larger increases in resistive losses. Further prospective
      validation characterizing M in well-defined pathological states is warranted.

PMID- 16575024
TI  - Hog barn dust extract increases macromolecular efflux from the hamster cheek
      pouch.
AB  - The purpose of this study was to determine whether short-term exposure to an
      aqueous extract of hog barn dust increases macromolecular efflux from the intact
      hamster cheek pouch and, if so, to begin to determine the mechanism(s) underlying
      this response. By using intravital microscopy, we found that suffusion of hog
      barn dust extract onto the intact hamster cheek pouch for 60 min elicited a
      significant, concentration-dependent leaky site formation and increase in
      clearance of FITC-labeled dextran (molecular mass, 70 kDa). This response was
      significantly attenuated by suffusion of catalase (60 U/ml), but not by heat
      inactivated catalase, and by pretreatment with dexamethasone (10 mg/kg iv) (P <
      0.05). Catalase had no significant effects on adenosine-induced increase in
      macromolecular efflux from the cheek pouch. Suffusion of hog barn dust extract
      had no significant effects on arteriolar diameter in the cheek pouch. Taken
      together, these data indicate that hog barn dust extract increases macromolecular
      efflux from the in situ hamster cheek pouch, in part, through local elaboration
      of reactive oxygen species that are inactivated by catalase. This response is
      specific and attenuated by corticosteroids. We suggest that plasma exudation
      plays an important role in the genesis of upper airway dysfunction evoked by
      short-term exposure to hog barn dust.

PMID- 16575025
TI  - Expiratory threshold loading impairs cardiovascular function in health and
      chronic heart failure during submaximal exercise.
AB  - We determined the effects of augmented expiratory intrathoracic pressure (P(ITP))
      production on cardiac output (Q(TOT)) and blood flow distribution in healthy dogs
      and dogs with chronic heart failure (CHF). From a control expiratory P(ITP)
      excursion of 7 +/- 2 cmH2O, the application of 5, 10, or 15 cmH2O expiratory
      threshold loads increased the expiratory P(ITP) excursion by 47 +/- 23, 67 +/-
      32, and 118 +/- 18% (P < 0.05 for all). Stroke volume (SV) rapidly decreased
      (onset <10 s) with increases in the expiratory P(ITP) excursion (-2.1 +/- 0.5%, 
      2.4 +/- 0.9%, and -3.6 +/- 0.7%, P < 0.05), with slightly smaller reductions in
      Q(TOT) (0.8 +/- 0.6, 1.0 +/- 1.1, and 1.8 +/- 0.8%, P < 0.05) owing to small
      increases in heart rate. Both Q(TOT) and SV were restored to control levels when
      the inspiratory P(ITP) excursion was augmented by the addition of an inspiratory
      resistive load during 15 cmH2O expiratory threshold loading. The highest level of
      expiratory loading significantly reduced hindlimb blood flow by -5 +/- 2% owing
      to significant reductions in vascular conductance (-7 +/- 2%). After the
      induction of CHF by 6 wk of rapid cardiac pacing at 210 beats/min, the expiratory
      P(ITP) excursions during nonloaded breathing were not significantly changed (8 +/
      2 cmH2O), and the application of 5, 10, and 15 cmH2O expiratory threshold loads
      increased the expiratory P(ITP) excursion by 15 +/- 7, 23 +/- 7, and 31 +/- 7%,
      respectively (P < 0.05 for all). Both 10 and 15 cmH2O expiratory threshold loads
      significantly reduced SV (-3.5 +/- 0.7 and -4.2 +/- 0.7%, respectively) and
      Q(TOT) (-1.7 +/- 0.4 and -2.5 +/- 0.4%, P < 0.05) after the induction of CHF,
      with the reductions in SV predominantly occurring during inspiration. However,
      the augmentation of the inspiratory P(ITP) excursion now elicited further
      decreases in SV and Q(TOT). Only the highest level of expiratory loading
      significantly reduced hindlimb blood flow (-4 +/- 2%) as a result of significant
      reductions in vascular conductance (-5 +/- 2%). We conclude that increases in
      expiratory P(ITP) production-similar to those observed during severe expiratory
      flow limitation-reduce cardiac output and hindlimb blood flow during submaximal
      exercise in health and CHF.

PMID- 16575026
TI  - Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation
      with long-term electrical stimulation training.
AB  - Understanding the torque output behavior of paralyzed muscle has important
      implications for the use of functional neuromuscular electrical stimulation
      systems. Postfatigue potentiation is an augmentation of peak muscle torque during
      repetitive activation after a fatigue protocol. The purposes of this study were
      1) to quantify postfatigue potentiation in the acutely and chronically paralyzed
      soleus and 2) to determine the effect of long-term soleus electrical stimulation
      training on the potentiation characteristics of recently paralyzed soleus muscle.
      Five subjects with chronic paralysis (>2 yr) demonstrated significant postfatigue
      potentiation during a repetitive soleus activation protocol that induced low
      frequency fatigue. Ten subjects with acute paralysis (<6 mo) demonstrated no
      torque potentiation in response to repetitive stimulation. Seven of these acute
      subjects completed 2 yr of home-based isometric soleus electrical stimulation
      training of one limb (compliance = 83%; 8,300 contractions/wk). With the early
      implementation of electrically stimulated training, potentiation characteristics
      of trained soleus muscles were preserved as in the acute postinjury state. In
      contrast, untrained limbs showed marked postfatigue potentiation at 2 yr after
      spinal cord injury (SCI). A single acute SCI subject who was followed
      longitudinally developed potentiation characteristics very similar to the
      untrained limbs of the training subjects. The results of the present
      investigation support that postfatigue potentiation is a characteristic of fast
      fatigable muscle and can be prevented by timely neuromuscular electrical
      stimulation training. Potentiation is an important consideration in the design of
      functional electrical stimulation control systems for people with SCI.

PMID- 16575027
TI  - Postnatal development of right atrial injection of capsaicin-induced apneic
      response in rats.
AB  - Apnea and respiratory failure often occur in infants with pulmonary disease.
      Bronchopulmonary C-fiber (PCF)-mediated apnea is an important component of
      respiratory dysfunction. This study was undertaken to define the postnatal
      development of PCF-mediated apnea. The experiments were conducted in five groups
      of anesthetized, tracheotomized, and spontaneously breathing rats with ages at
      postnatal days P1-3, P7-9, P14-16, P21-23, and P56-58. Right atrial bolus
      injection of three doses of capsaicin (Cap), equivalent to 2, 4, and 8 microg/kg
      used previously in 450-g rats, was applied to stimulate PCFs. We found that 1)
      Cap-induced apneic response [percent change from the baseline expiratory duration
      (Te) values (deltaTe%)] and the sensitivity of this response (deltaTe%.microg(
      1)) were significantly greater in the rats <P10 than those >P10; 2) the Cap
      induced apneas were vagally dependent in all rats tested; and 3) bivagotomy
      induced prolongation of Te was much greater in the rats <P10 than those >P10.
      From these findings we concluded that, compared with the older rats (>P10), the
      newborn rats have a stronger PCF-mediated respiratory inhibition that may
      contribute to infants' vulnerability to respiratory failure.

PMID- 16575028
TI  - Optimizing transfusion practice.

PMID- 16575029
TI  - Preemptive use of recombinant activated factor VII: many questions but few
      answers.

PMID- 16575030
TI  - Training and development of anesthesia in Nepal - 1985 to 2005.
AB  - PURPOSE: To describe the self-sustaining anesthesia training and development
      program in Nepal from 1985 through 2005, and the Canadian contributions. METHODS:
      We examined the training program and outcome of the diploma in anesthesia (DA)
      and MD anesthesiology programs in Nepal over a 20-year period. Issues related to
      recruitment, funding, specialist training opportunities and professional
      development were examined and summarized. RESULTS: In 1985 there were seven
      Nepalese physician anesthesiologists in Nepal. With Canadian support of faculty
      members and the Canadian Anesthesiologists' Society International Education Fund,
      a one-year DA training program began in 1985, and a three-year MD anesthesia
      program began in 1996. As of 2005, 43 anesthesiologists were trained in the DA
      program, and 19 Nepalese completed MD anesthesia training. Thirteen (30%) of DA
      graduates have since left the country, compared to only two (10.5%) physicians
      from the MD anesthesia training program. Annual anesthesia symposia began in
      1986, and the Society of Anesthesiologists of Nepal was formed in 1987. Nepalese
      anesthesiologists have been attending and presenting papers at international
      scientific meetings since 1991. CONCLUSION: The devotion of Nepalese
      anesthesiologists in teaching and training, strong guidance from Canadian medical
      faculties, and local government support have contributed to the successful
      development of Nepalese anesthesia training programs. Establishment of the
      training programs has assisted recruitment of trained anesthesiologists to
      different regional hospitals. Finally, the formation of a national society, with
      an organized annual symposium has improved professional self-esteem, and raised
      the profile of anesthesiology in Nepal.

PMID- 16575031
TI  - Red blood cell transfusion practices amongst Canadian anesthesiologists: a
      survey.
AB  - PURPOSE: To assess red blood cell transfusion practices among Canadian
      anesthesiologists. METHODS: A survey depicting three realistic clinical scenarios
      of elective surgical procedures with different risks of bleeding was administered
      to all Canadian practicing members (n = 2,100) of the Canadian Anesthesiologists'
      Society. Respondents were requested to choose hemoglobin thresholds for which
      they would transfuse red blood cells under various conditions within each
      scenario. RESULTS: We obtained a response rate of 47% (719/1,512). Transfusion
      thresholds differed significantly between baseline scenarios. A threshold above
      70 g x L(-1) was chosen by 48% of respondents in the general surgery scenario
      compared to 56% in the orthopedic surgery scenario and 79% in the vascular
      surgery scenario (P < 0.001). A history of coronary artery disease was associated
      with a transfusion threshold >or= 100 g x L(-1) in a significant proportion of
      respondents ranging from 20% in the orthopedic surgery scenario to 31% in the
      general surgery scenario and to 49% in the vascular surgery scenario (P < 0.001).
      Conversely, changing the patient's age from 60 to 20 yr resulted in the adoption
      of a transfusion threshold <or= 60 g x L(-1) by > 30% of respondents in two
      scenarios (P < 0.001). The year of respondent graduation was strongly associated
      with these findings. CONCLUSION: There was significant variation in transfusion
      practices among Canadian anesthesiologists. The type of surgical procedure,
      patient's age and a history of coronary artery disease influenced reported
      transfusion threshold. Practice variation in specific subgroups would support the
      need for further research to identify optimal transfusion thresholds.

PMID- 16575032
TI  - Aortic dissection and hypothermic arrest in a Jehovah's Witness patient: a case
      for recombinant factor VIIa?
AB  - PURPOSE: To present a case of survival of a cognitively intact Jehovah's Witness
      patient with an aortic dissection who underwent hypothermic arrest. Recombinant
      factor VIIa, but no blood products were administered. CLINICAL FEATURES: An 83-yr
      old female with an acute type A aortic dissection underwent emergent surgical
      repair. Proximal extension of the dissection necessitated prolonged
      cardiopulmonary bypass (CPB) and hypothermic circulatory arrest. Despite this,
      perioperative hemostatis was adequate. Recombinant factor VIIa 90 microg x kg(-1)
      i.v. was administered post-CPB. The patient had an uneventful postoperative
      course, and was discharged home neurologically intact. CONCLUSIONS: Patients who
      conscientiously object to the transfusion of blood products may present a
      considerable anesthetic challenge, especially those at risk from coagulopathy
      associated with CPB and hypothermic circulatory arrest. Recombinant factor VIIa
      may play a role in hemostasis management of these individuals, however, well
      designed randomized controlled trials need to be undertaken to establish the
      efficacy and risks related to this potential indication.

PMID- 16575033
TI  - Remifentanil versus propofol for radio frequency treatment of atrial flutter.
AB  - PURPOSE: Radio frequency treatment in cardiology generates short acute pain
      during the heating process. The present study evaluates two techniques used for
      sedation/analgesia for this procedure. METHODS: Two groups of 20 patients each
      were studied prospectively. Patients were randomized to receive sedation for the
      procedure using either a patient-controlled analgesia device with remifentanil
      (Group R), or a target controlled infusion of propofol (Group P). Patients in
      Group R had a basal infusion of remifentanil 0.02-0.04 microg x kg(-1) x min(-1)
      with self administered bolus doses of 0.3 microg x kg(-1) i.v. every minute as
      required, with a delivery time greater than 30 sec. Patients in Group P had an
      initial plasma target concentration set at 3-4 microg x mL(-1). RESULTS: Sedation
      scores were significantly higher in Group P, and two patients required
      supplementation with remifentanil and insertion of an laryngeal mask airway. Pain
      scores were higher in Group R, and two patients experienced muscular rigidity,
      one with transient apnea. Systolic blood pressure decreased significantly in
      Group P, and at the end of the procedure, PaCO(2) values were higher in that
      group (P < 0.01). Recovery time was significantly longer in Group P. Patient and
      physician satisfaction scores were similar in the two groups. CONCLUSIONS: A
      basal infusion of remifentanil plus remifentanil patient controlled analgesia and
      target controlled infusion of propofol were adequate but not optimal techniques
      for sedation/analgesia for radio frequency treatment of atrial flutter.

PMID- 16575034
TI  - Bispectral index and regional cerebral oxygen saturation during propofol/N2O
      anesthesia.
AB  - PURPOSE: A study was undertaken to compare the influence of midazolam,
      isoflurane, and aminophylline (which may antagonize anesthetic action) on
      bispectral index (BIS) and regional cerebral oxygen saturation (rSO(2)) during
      propofol/N(2)O anesthesia, and to test the hypothesis that the drug-induced
      changes in BIS values are accompanied by a change in rSO(2). METHODS: General
      anesthesia was administered to 36 patients with a continuous infusion of propofol
      to maintain a BIS value of 40 +/- 5. After baseline recordings, patients were
      randomly assigned to receive either midazolam, isoflurane, or aminophylline.
      Bispectral index values, rSO(2) using near-infrared spectroscopy, and hemodynamic
      parameters were recorded for 60 min. RESULTS: Midazolam (0.05 mg x kg(-1))
      significantly decreased the BIS from 47.8 +/- 5.4 to 35.0 +/- 4.5 at five minutes
      after injection (P < 0.001 vs control) during propofol anesthesia, whereas the
      rSO(2) was unchanged. Similarly, isoflurane (1.1% end-tidal) decreased the BIS
      from 42.5 +/- 7.5 to 27.8 +/- 6.9 (P < 0.001) without affecting rSO(2). In
      contrast, aminophylline (3 mg.kg(-1)) was associated with an increase in BIS from
      41.6 +/- 2.1 to 48.3 +/- 9.2 at five minutes after injection (P < 0.05) without
      affecting rSO(2). CONCLUSIONS: Midazolam or isoflurane-induced decreases in the
      BIS during propofol anesthesia were not accompanied by a decrease in rSO(2).
      Aminophylline significantly increased the BIS score during propofol anesthesia,
      suggesting that aminophylline can antagonize, at least in part, the sedative
      actions of propofol.

PMID- 16575035
TI  - Betamethasone does not prevent nausea and vomiting induced by the dopamine
      agonist apomorphine.
AB  - PURPOSE: The mechanism of the antiemetic actions of corticosteroids is not known.
      The purpose of this study was to evaluate if betamethasone can prevent nausea,
      vomiting or increase of vasopressin induced by apomorphine. Metoclopramide, a
      dopamine antagonist, was used as a control substance. METHODS: Ten healthy
      volunteers were studied on three occasions. In a randomized order they were
      allocated to receive pretreatment with betamethasone 8 mg iv, metoclopramide 10
      mg iv, and normal saline 2 mL as placebo on the three different occasions, 15 min
      before the administration of apomorphine 30 microg x kg(-1) s.c.. After
      administration of apomorphine, episodes of vomiting were recorded, and the
      intensity of nausea was estimated by the subject on a visual analogue scale (VAS
      0-10 cm). Blood samples for analysis of plasma concentrations of vasopressin were
      analyzed. RESULTS: One volunteer decided to withdraw, as he experienced akathisia
      after receiving metoclopramide. During the first two hours after apomorphine,
      eight of nine volunteers vomited both after betamethasone and placebo. One
      volunteer did not vomit after betamethasone and placebo but he experienced
      nausea. None of the volunteers vomited after metoclopramide (P < 0.01 vs
      betamethasone and placebo). The maximum VAS for nausea was significantly higher
      after betamethasone and placebo compared to metoclopramide (P < 0.01). The
      vasopressin levels increased after betamethasone and placebo, but there was no
      increase in any volunteer after pretreatment with metoclopramide. CONCLUSION:
      This study demonstrates that betamethasone does not prevent nausea, vomiting and
      increase of vasopressin induced by apomorphine, whereas metoclopramide prevents
      apomorphine-induced emesis. Our work suggests that betamethasone does not have
      dopamine-antagonistic effects.

PMID- 16575036
TI  - Targeted thoracic epidural blood patch placed under electrical stimulation
      guidance (Tsui test).
AB  - PURPOSE: This case report describes the use of electrical epidural stimulation
      (Tsui test) to confirm accurate placement of a thoracic epidural catheter when
      administering an epidural blood patch for headache management in a patient
      suffering from spontaneous intracranial hypotension. CLINICAL FEATURES: A 41-yr
      old female presented to the Chronic Pain Clinic with a history of postural
      headache symptoms worsening in severity over several years. Two previous blood
      patches performed at T11-12 and T10-11 respectively provided short-term relief
      only. The presumed diagnosis of a spontaneous dural tear was confirmed by a
      nuclear flow test to be at T2-T4. The epidural site was accessed at T6 with a
      Tuohy needle. To accurately place the epidural blood patch at the level of the
      dural tear, the Arrow catheter with electrode adapter was advanced under nerve
      stimulation guidance to T4. Ten millilitres of autologous blood injected through
      the catheter was confirmed on magnetic resonance imaging, one hour postprocedure,
      to lie between T3 and T9. Sustained headache relief was achieved. CONCLUSION: The
      use of electrical stimulation guidance may be useful when precise epidural blood
      patch placement is required.

PMID- 16575037
TI  - Anesthetic management of a labouring parturient with urticaria pigmentosa.
AB  - PURPOSE: To report the anesthetic management of labour pain and Cesarean section
      in a patient with urticaria pigmentosa at risk for systemic mastocytosis.
      CLINICAL: A 37-yr-old patient with a history of urticaria pigmentosa and an
      allergic reaction to a local anesthetic agent was seen in consultation at 36
      weeks gestation. She previously tested negative for an allergy test to lidocaine.
      Recommendations to avoid systemic mastocytosis included: avoidance of histamine
      releasing drugs, using lidocaine for labour epidural, and regional anesthesia in
      case of a Cesarean section. The patient presented at term in labour. Intravenous
      fentanyl was used for early labour, followed by a combined spinal-epidural. The
      spinal contained lidocaine and fentanyl, but because of pruritus, the epidural
      infusion contained lidocaine only. Most likely because of tachyphylaxis to
      lidocaine, an epidural bolus of lidocaine with epinephrine failed to provide
      adequate anesthesia for a Cesarean section. The block was supplemented with
      nitrous oxide by mask, with fentanyl postdelivery. Postoperative pain control was
      managed with an epidural infusion of lidocaine and fentanyl for three days. The
      patient was discharged without complications four days postsurgery. CONCLUSION:
      Proper allergy testing prior to pregnancy is important to help the management of
      labour pain and anesthesia for Cesarean section in a patient at risk for systemic
      mastocytosis.

PMID- 16575038
TI  - Postoperative tracheal rupture in a patient with a difficult airway.
AB  - PURPOSE: Tracheal rupture is an uncommon and potentially life-threatening event.
      This report presents a case of postoperative tracheal rupture in a patient with a
      known difficult airway presenting to a rural hospital. CLINICAL FEATURES: A 29-yr
      old man presented to a rural hospital with sudden onset neck pain and progressive
      dyspnea. Five days earlier the patient had undergone tracheal resection for
      tracheal stenosis related to prolonged intubation. The patient informed the
      emergency room staff that the attending anesthesiologist had made note of a
      "difficult airway". The community hospital had neither a portable storage unit
      for difficult airway management nor a bronchoscope available. In the presence of
      a general surgeon, an initial attempt at an awake intubation was unsuccessful.
      During this time the patient developed massive subcutaneous emphysema
      obliterating surgical landmarks and causing stridor. A modified rapid sequence
      intubation was performed. Intubation was successful using a Jackson-Wisconsin #3
      straight blade and styletted endotracheal tube. The patient was transferred to a
      tertiary care centre where he underwent a primary repair of the trachea.
      CONCLUSION: Management of tracheal rupture in the patient with a difficult airway
      is a challenging problem, especially, in a rural hospital. This case highlights
      the need for skilled staff and resources to manage a difficult airway in the
      emergency room.

PMID- 16575039
TI  - Laryngeal edema associated with the ProSeal laryngeal mask airway in upper
      respiratory tract infection.
AB  - PURPOSE: We report an unusual case of vocal cord edema associated with the use of
      a ProSeal laryngeal mask airway (PLMA) in an adult patient with an undiagnosed
      upper respiratory tract infection (URTI). CLINICAL FEATURES: A 55-yr-old woman
      had fixation of a radial fracture under general anesthesia with muscle
      relaxation. She developed audible wheezing 30 min after PLMA insertion.
      Bronchoscopic examination revealed significant vocal cord edema. Adequate
      ventilation was possible at increased airway pressures, and the administration of
      dexamethasone 4 mg iv produced clinical resolution of the stridor and airway
      obstruction. The patient admitted to having mild symptoms of an URTI on
      postoperative questioning. CONCLUSION: Airway hyperreactivity secondary to the
      URTI is the most likely etiological factor; other possibilities include trauma
      from insertion and chemical irritation. Although pediatric studies suggest that
      the LMA-Classic carries less risk than endotracheal intubation in the presence of
      URTI, this case report demonstrates that caution is still warranted when using
      supraglottic airways. The PLMA permitted effective ventilation despite increased
      airway resistance; nevertheless its role in patients with URTI is unclear. It is
      possible that the bulkier cuff design of the PLMA, compared to that of the LMA
      Classic, may have partly contributed to the development of edema in this setting.

PMID- 16575040
TI  - Preoperative predictors of difficult intubation in patients with obstructive
      sleep apnea syndrome.
AB  - PURPOSE: It has been speculated that the severity of obstructive sleep apnea
      syndrome (OSAS) is related to difficult intubation. However, this has not been
      confirmed in OSAS patients. Thus, we undertook a retrospective study to assess
      this relationship in patients who had undergone uvulopalatopharyngoplasty (UPPP)
      surgery for OSAS. METHODS: A retrospective case-control study was undertaken
      following approval from the Institutional Review Board on human studies. The data
      from 90 patients with a polysomnograph-confirmed diagnosis of OSAS, who had
      undergone UPPP surgery under general anesthesia, were used to evaluate the apnea
      hypopnea index (AHI), the preoperative lowest arterial saturation, the occurrence
      of difficult intubation as assessed by the operator intubation difficulty scale
      score, extubation time, lowest arterial saturation in postanesthesia care unit,
      and length of stay in postanesthesia care unit. We compared OSAS patients with 90
      age and sex-matched control patients with respect to the prevalence of difficult
      intubation. RESULTS: The prevalence of difficult intubation was higher in the
      OSAS group than in the control group (16.7% vs 3.3%, P = 0.003). When evaluating
      the OSAS group according to the occurrence of difficult intubation, AHI was
      significantly higher in the difficult intubation subgroup (67.4 +/- 22.5 vs 49.9
      +/- 28.0, P = 0.026), and patients with an AHI >or= 40 showed a significantly
      higher prevalence of difficult intubation. CONCLUSION: This study shows that the
      occurrence of difficult intubation can be predicted using AHI in patients who
      undergo UPPP surgery for OSAS.

PMID- 16575041
TI  - Suction catheter guided insertion of the ProSeal laryngeal mask airway is
      superior to the digital technique.
AB  - PURPOSE: We tested the hypothesis that digital insertion of the ProSeal laryngeal
      mask airway (ProSeal LMA) is more successful when using a suction catheter (SC)
      as a guide. METHODS: Two hundred and forty-three patients (ASA physical status I
      III; aged 18-84 yr) were randomly allocated for the digital or SC-guided
      technique. The digital technique was performed according to the manufacturer's
      instructions. The SC technique involved priming the drain tube with the SC so
      that it protruded by 15 cm, blindly inserting the SC into the pharynx to a depth
      of 15 cm, followed by the digital technique. Failed insertion was defined by any
      of the following criteria: 1) failed passage into the pharynx; 2) malposition;
      and 3) ineffective ventilation. Any airway trauma, and visible or occult blood
      was noted. Sore throat, dysphonia and dysphagia were assessed 16 to 24 hr
      postoperatively. RESULTS: Fewer insertion attempts were required with the SC
      guided technique (P = 0.02), but first attempt and overall success were similar.
      The time taken to provide an effective airway was shorter for the SC-guided
      technique (36 +/- 24 sec vs 44 +/- 28 sec, P = 0.02). A lateral approach was
      required less frequently with the SC-guided technique (0% vs 4%, P = 0.0004).
      There were no adverse events. Mouth trauma was more frequent with the digital
      technique (P = 0.04), but overall trauma was similar. There were no differences
      in the frequency of visible or occult blood. There were no differences in
      postoperative airway morbidity. CONCLUSIONS: The SC-guided technique is more
      frequently successful than the digital technique and is associated with less
      mouth trauma during insertion of the ProSeal LMA. We suggest that the SC
      technique may be a useful alternative when the digital technique fails.

PMID- 16575042
TI  - Non-invasive ventilation corrects alveolar hypoventilation during spinal
      anesthesia.
AB  - PURPOSE: To document and explain the beneficial effects of non-invasive
      ventilation in correcting hypoxemia and hypoventilation in severe chronic
      obstructive pulmonary disease, during spinal anesthesia in the lithotomy
      position. CLINICAL FEATURES: A morbidly obese patient with severe chronic
      obstructive pulmonary disease underwent prostate surgery in the lithotomy
      position under spinal anesthesia. Hypoxemia was encountered during surgery, and a
      profound decrease of forced vital capacity associated with alveolar
      hypoventilation and ventilation/perfusion mismatching were observed. In the
      operating room, an M-mode sonographic study of the right diaphragm was performed,
      which confirmed that after spinal anesthesia and assuming the lithotomy position,
      there was a large decrease (-30%) in diaphragmatic excursion. Hypoxemia and
      alveolar hypoventilation were successfully treated with non-invasive positive
      pressure ventilation. CONCLUSIONS: Intraoperative application of non-invasive
      positive pressure ventilation improved diaphragmatic excursion and overall
      respiratory function, and reduced clinical discomfort in this patient.

PMID- 16575043
TI  - Arterial to end-tidal CO2 laparoscopic gradient reversal during pheochromocytoma
      resection.
AB  - PURPOSE: We report the development of severe intraoperative hypercarbia and a
      pronounced arterial to end-tidal gradient reversal during laparoscopic
      pheochromocytoma resection. Although complex physiologic mechanisms may be
      responsible for this finding, anatomic alterations such as a direct communication
      between a capnoperitoneum and/or capnothorax and the airways resulting from prior
      pathology and the type of procedure should also be considered. CLINICAL FEATURES:
      During anesthesia for laparoscopic pheochromocytoma removal we noticed an abrupt,
      extensive increase of the end-tidal CO(2) accompanied by a change of the
      capnographic CO(2) tracing and reversal of the normal arterial-to-end-tidal
      gradient. These changes consistently disappeared by intermittent deflation of the
      abdomen and at the end of surgery. A chest x-ray revealed a right-sided loculated
      pneumothorax with pleural thickening. Peritoneo-thoracic CO(2) tracking and
      pleural scaring with pulmonary adhesions resulting in a unidirectional
      communication between the pleural space and airways may best explain the chest x
      ray and clinical findings. CONCLUSION: Severe intraoperative hypercarbia and
      arterial to end-tidal CO(2) gradient reversal represents an intraoperative
      challenge. The possibility of a direct communication between the pleural space
      and the bronchial tree should be considered when other etiologies have been
      excluded. Simple maneuvers such as abdominal de- and re-inflation and analysis of
      the end-tidal capnographic tracing might aid in the differential diagnosis and
      management.

PMID- 16575045
TI  - Objective techniques for identification of the epidural space in infants and
      children.

PMID- 16575046
TI  - Vision loss after spine surgery: a new hypothesis.

PMID- 16575047
TI  - Factors which may influence mean arterial pressure measurement.

PMID- 16575048
TI  - Radiographic confirmation following pediatric femoral venous cannulation.

PMID- 16575049
TI  - The GlideScope video laryngoscope: initial experience in five neonates.

PMID- 16575050
TI  - Verifying spinal needle location in the presence of a "dry tap".

PMID- 16575051
TI  - Access to antiretrovirals still too scarce in many countries.

PMID- 16575052
TI  - Reforming mental health law in England and Wales.

PMID- 16575053
TI  - Increasing the number of medical students from under-represented minorities.

PMID- 16575055
TI  - NHS faces job cuts as financial crisis deepens.

PMID- 16575054
TI  - Managing challenging behaviour in dementia.

PMID- 16575056
TI  - African doctors abroad need to work together to improve health care at home.

PMID- 16575057
TI  - Non-European doctors feel penalised by change in UK policy.

PMID- 16575060
TI  - Dutch doctors campaign for smoking ban in hospitality industry.

PMID- 16575061
TI  - Germany may change drug testing rules after debacle in England.

PMID- 16575062
TI  - People considering laser eye surgery should be warned of risks, says NICE.

PMID- 16575063
TI  - Critically ill men in drug trial continue to improve.

PMID- 16575065
TI  - GMC finds three doctors guilty of irresponsible prescribing to addicts.

PMID- 16575066
TI  - Faking happiness at work can make you ill.

PMID- 16575067
TI  - GMC finds no case to answer against Ian Craft.

PMID- 16575068
TI  - Trust's refusal to fund trastuzumab was "arbitrary".

PMID- 16575075
TI  - Assisted conception business should be better regulated.

PMID- 16575076
TI  - AIDS robs millions of their childhood.

PMID- 16575078
TI  - Asthma control in adults.

PMID- 16575079
TI  - Hip dislocation in cerebral palsy.

PMID- 16575080
TI  - Secondary drowning in a patient with epilepsy.

PMID- 16575081
TI  - Wound dressings.

PMID- 16575084
TI  - Using lessons from the past to plan for pandemic flu.

PMID- 16575085
TI  - UK government response to Hilary Pickles.

PMID- 16575086
TI  - An iatrogenic pandemic of panic.

PMID- 16575087
TI  - A slippery disease: a microbiologist's view.

PMID- 16575088
TI  - Hard decisions will have to be made: view from intensive care.

PMID- 16575089
TI  - Dealing with uncertainty: perspective from primary care.

PMID- 16575090
TI  - Blood pressure lowering in elderly patients with stroke.

PMID- 16575091
TI  - Preventing coronary heart disease: patients are people, not cases.

PMID- 16575092
TI  - Preventing coronary heart disease: high baseline risk strategy and cost
      effectiveness of guidelines.

PMID- 16575093
TI  - Grieving the death of a child: supporting health professionals who care for
      grieving patients may benefit all.

PMID- 16575094
TI  - Grieving the death of a child: clinicians should ensure that lethal drugs are
      handed back.

PMID- 16575095
TI  - Estimated glomerular filtration rate needs UK consensus.

PMID- 16575096
TI  - Googling your treatment for analgesia in labour.

PMID- 16575097
TI  - Time to make paracetamol with methionine available.

PMID- 16575098
TI  - Gluteal injections in increasingly obese population: essential considerations for
      intramuscular injections.

PMID- 16575099
TI  - Gluteal injections in increasingly obese population: needle length for
      intramuscular injections.

PMID- 16575101
TI  - Untreated controls are wrong when proved treatment exists.

PMID- 16575104
TI  - Publish no evil : should editors publish research that could have dual-use?

PMID- 16575102
TI  - Independent sector treatment centres: experience and spin.

PMID- 16575105
TI  - Comments on the new analysis of the Chingleput BCG trial.

PMID- 16575106
TI  - TB control - a long way to go.

PMID- 16575107
TI  - Effect of myocardial ischaemia & reperfusion on brain.

PMID- 16575108
TI  - Drug resistance in amoebiasis.
AB  - Amoebiasis caused by Entamoeba histolytica, is a major public health problem in
      developing countries. Morphologically similar E. dispar is non pathogenic.
      Because of the redefinition of E. histolytica and E. dispar, and the limited
      number of antiamoebic drugs available, a new approach to treat such individuals
      is necessary. The cost of treating asymptomatic individuals is highly exorbitant
      and not justifiable. The indiscriminate use of antiamoebic drugs can result in
      increased minimum inhibitory concentration (MIC) values against Entamoeba
      species, and treatment failure may emerge as an important public health problem.
      Development of new antiamoebic drugs is still in infancy and vaccine development
      appears to be distant dream. In future, the development of drug resistance may
      seriously affect the control of disease. This review discusses the factors
      involved in drug resistance mechanisms developed by the parasite.

PMID- 16575109
TI  - Influence of sex, age & nontuberculous infection at intake on the efficacy of
      BCG: re-analysis of 15-year data from a double-blind randomized control trial in
      South India.
AB  - BACKGROUND & OBJECTIVE: To estimate the efficacy of BCG in preventing
      tuberculosis over a 15-year period, and also to assess the impact of infection
      with nontuberculous environmental mycobacteria in a rural community in Chingleput
      district in Tamil Nadu in south India. We re-analysed the 15-year follow up data
      of a large randomized trial conducted earlier. METHODS: A double-blind randomized
      control trial was initiated in 1968, in which over 100,000 uninfected subjects
      with a normal radiograph were allocated to placebo, BCG in low dose (0.01 mg) or
      BCG in high dose (1.0 mg); two widely used strains of BCG were employed, each in
      one half of the vaccinated subjects. Sensitivity to purified protein derivative
      (PPD-B) was also determined. The study population was followed for 15 yr by
      radiographic surveys of the total population once every 2.5 yr, selective case
      finding in suspects once in 10 months, and investigation of those reporting
      voluntarily with chest symptoms. RESULTS: Coverage by radiography was of the
      order of 80 per cent throughout, while coverage by sputum examination of suspects
      was usually 90 per cent or above. The annual incidence of culture-positive
      tuberculosis (irrespective of smear) was estimated to be 55 per 100,000, and
      neither strain of BCG had any effect. The failure to protect was seen in both
      males and females, and in children and adults. However, in a subset of over
      40,000 subjects who were also nonreactors to PPD-B, BCG had a low level of
      protection, i.e., 32 per cent (95% CI=3-52%), 29 per cent with the Danish strain
      and 34 per cent with the French strain. INTERPRETATION & CONCLUSION: Our findings
      reaffirm that BCG was of little value in preventing sputum-positive cases of
      pulmonary tuberculosis.

PMID- 16575110
TI  - Simultaneous ethambutol & isoniazid resistance in clinical isolates of
      Mycobacterium tuberculosis.
AB  - BACKGROUND & OBJECTIVE: There is a need to understand the nature of drug
      resistance patterns and predictors of emergence of drug resistance in
      Mycobacterium tuberculosis. There could be common factors/mechanisms for
      resistance to the drugs, isoniazid and ethambutol, both acting on cell wall. The
      present study was conducted to analyze the antimycobacterial susceptibility
      patterns of M. tuberculosis isolates to determine the minimum inhibitory
      concentrations (MICs) of ethambutol for M. tuberculosis; and to find out possible
      association of ethambutol resistance with isoniazid resistance. METHODS: A total
      of 380 M. tuberculosis isolates were tested for their susceptibilities to
      ethambutol at 2, 4, 6 microg/ml, isoniazid at 1 microg/ml and rifampicin at 64
      microg/ml using MIC method. RESULTS: 44.21, 24.73 and 14.21 per cent isolates
      were resistant to ethambutol at concentrations of 2, 4 and 6 microg/ml
      respectively. At 6 microg/ml of ethambutol concentration, 85.18 per cent
      ethambutol resistant isolates were resistant to isoniazid also. At the same
      ethambutol concentration a fraction of 28.75 per cent isoniazid resistant
      isolates were ethambutol resistant. INTERPRETATION & CONCLUSION: Ethambutol
      resistance was accompanied with isoniazid resistance in a large percentage of
      isolates whereas ethambutol resistance was weakly linked with multidrug
      resistance. On the other hand, association between isoniazid and ethambutol
      resistance was weak showing one way linkage.

PMID- 16575111
TI  - Changes in the expression of c-fos & heat shock protein genes & blood flow
      velocity in the brain of rats undergoing myocardial ischaemia/reperfusion.
AB  - BACKGROUND & OBJECTIVE: Myocardial hypofunction could lead to the derangement of
      brain functions. The expression of c-fos and heat shock protein (hsp) genes was
      recognized as markers of neural cell injury. We under took this study to
      investigate the influence of myocardial ischaemia and reperfusion (I/R) on these
      molecular events in the rat brain tissue and changes in mean arterial blood
      pressure (MAP) and the cerebral blood flow velocity (CBFV), to understand the
      basis of cerebral pathology following cardiac ischaemia and reperfusion. METHODS:
      Healthy rats (n=42) were randomly allocated into seven groups: sham-operated (A);
      myocardial ischaemia for 15 min, followed by 0.5, 1, 2, 4 and 6 h of reperfusion
      respectively (B2-B6) and hypovolemia at medium level (C). I/R rat models were
      established by ligating the anterior branch of the left coronary artery.
      Expressions of the c-fos, hsp70, hsp27 and hsp90 genes in the cerebrum,
      cerebellum, medullaoblongata and hippocampus, were studied with
      immunohistochemistry and in situ hybridization. The MAP and CBFV of the rats were
      also measured. RESULTS: The expressions of c-fos and HSP70 in brain tissue
      increased after myocardial ischaemia/ reperfusion, with the strongest signal
      appearing in the hippocampus and cerebral cortex, while labeling for HSP27 and
      HSP90 alpha were not detectable in any of the experimental groups. The
      expressions of c-fos mRNA and hsp70 mRNA shared the similar characteristics with
      their encoding proteins. MAP, reflection of cardiac function and cerebral blood
      flow decreased following cardiac ischaemia and reperfusion. INTERPRETATION &
      CONCLUSION: Our findings suggested that the brain damages occurred from the early
      phase of myocardial I/R. The exact mechanism of cerebral tissue injuries induced
      by myocardial I/R is not known. Further studies need to be done to throw light on
      these aspects.

PMID- 16575112
TI  - Genotype analysis of human Mycobacterium avium isolates from India.
AB  - BACKGROUND & OBJECTIVE: Mycobacterium avium has emerged as a major opportunistic
      pathogen, infecting nearly 50 per cent of HIV/AIDS patients in the western world.
      There is no report from India regarding the typing profile of M. avium, a
      potential pathogen, the present study was undertaken to assess the genotypic
      diversity of Indian M. avium isolates of human origin. METHODS: A total of 65
      biochemically identified M. avium isolates from sputum samples of patients with
      chronic pulmonary illness were subjected to IS1245 based restriction fragment
      length polymorphism (RFLP) and polymerase chain reaction (PCR) typing. RESULTS:
      IS1245 insertion sequence based RFLP demonstrated polymorphism in 84.6 per cent
      isolates, while 15.4 per cent isolates did not hybridize on Southern blot and
      therefore were RFLP negative. Among the 55 RFLP positive isolates, 8 showed 1-3
      bands, 19 had bands ranging between 4-9, and 28 isolates had >10 bands each.
      Although the isolates could be clubbed on the basis of number of bands, the
      banding profile was highly polymorphic. Among the 55 isolates typeable by RFLP,
      four clusters and 40 unique types of polymorphism were observed. Application of
      IS1245 based PCR typing on the same isolates showed that 87.7 per cent isolates
      were typeable. Interestingly the 10 isolates that were not typeable by IS1245
      RFLP were typeable by IS1245 based PCR typing. Among the 57 PCR typed isolates a
      cluster of 14 isolates with identical 3-banded pattern was observed. Notably, 5
      of the ten IS1245 RFLP negative isolates were within this cluster. INTERPRETATION
      & CONCLUSION: Our results demonstrated that M. avium isolates from India were
      highly polymorphic with remarkable genetic diversity and heterogeneous RFLP
      profile. We observed that 47 per cent (n=27) isolates had RFLP profile suggestive
      of bird and animal origin indicating a strong association with the environment.
      By applying two typing methods based on IS1245 on the isolates 100 per cent
      typeability could be achieved.

PMID- 16575113
TI  - Isolation & antimicrobial susceptibility of Shigella from patients with acute
      gastroenteritis in Western Nepal.
AB  - BACKGROUND & OBJECTIVE: Shigellae play an important role as a causative organism
      of acute gastroenteritis, which is a global health problem with significant
      morbidity and mortality in especially in developing countries. This study was
      carried out to determine the isolation and pattern of antimicrobial resistance of
      Shigella in patients with acute gastroenteritis in western Nepal. METHODS: The
      study included all patients with acute gastroenteritis who visited a tertiary
      care hospital at Pokhara, Nepal during a 2-year period (2002-2004). The isolates
      was confirmed as Shigella by biochemical reaction and slide agglutination test
      using specific antisera. Antibiotic sensitivity test was determined by agar
      diffusion method and minimum inhibitory concentration (MIC) of the drugs was
      detected. RESULTS: Of the 770 stool samples, 83 (10.8%) yielded Shigella.
      Shigella flexneri caused 56 (67.4%) of the total cases of shigellosis followed by
      S. dysenteriae 12 (14.5%), S. sonnei 10 (12%) and S. boydii 5 (6%). Of the 83
      isolates, 67 (80.7%) showed resistance to various drugs and 62 (74.7%) were
      resistant to two or more drugs. Resistance to cotrimoxazole was 80.7 per cent
      followed by tetracycline 74.7 per cent, ampicillin 53.0 per cent, nalidixic acid
      31.3 per cent and ciprofloxacin 2.4 per cent. The MIC(50) and MIC(90) values of
      those drugs were also very high. All isolates were sensitive to cefotaxime and
      ceftriaxone. INTERPRETATION & CONCLUSION: The findings of our study suggested
      that Shigellae was an important etiological agent for acute gastroenteritis, with
      a high rate of drug resistance and requires constant monitoring in this region.

PMID- 16575114
TI  - Relationship between Anopheles fluviatilis & A. stephensi (Diptera: Culicidae)
      catches & the prevalence of malaria cases at Kalsi area in Dehradun district
      (Uttaranchal).
AB  - BACKGROUND & OBJECTIVE: Though the relationship between mosquito density and
      transmission of malaria in different regions of the country is known, no studies
      are available on the relationship between mosquito catches and malaria cases in
      Kalsi area of Dehradun district in Uttaranchal. Hence, the present study was done
      to evaluate the role of anopheline mosquitoes catches and prevalence of malaria
      cases in this area. METHODS: During three consecutive years (2000-2003)
      mosquitoes were collected from 10 villages in Kalsi area twice a month, during
      the morning and evening hours. Identification of anopheline mosquitoes was done.
      Indoor collected female mosquitoes were dissected to see infection. Sporozoites
      were fixed and stained. Data on temperature and rainfall were also collected.
      RESULTS: As many as 10 species of anophelines were collected during three
      consecutive years - January 2000 to December 2002 at Kalsi block in district
      Dehradun (Uttaranchal). Proportion of the total anopheline species as well as the
      abundance of Anopheles stephensi was found more in the year 2002 than in 2000 and
      2001. Incrimination studies revealed malarial infection (sporozoite positive) in
      A. fluviatilis and A. stephensi. Of the 5450 blood smears examined, only 50
      (0.91%) were found positive for malarial parasite i.e., Plasmodium vivax. There
      was no case of P. falciparum during the study period. Highest slide positive rate
      (SPR) of 1.107 per cent was recorded in 2002 while in 2001, highest month-wise
      malaria positive cases were recorded in the month of August. September shared
      highest positive cases during 2000 and 2002. While correlating a relationship
      between mosquito catch especially infected ones and monthly parasite incidence,
      the density of A. stephensi showed significantly high correlation (r = 0.819;
      P<0.001). A slight variation in this type of relationship was seen in A.
      fluviatilis. Both temperature and rainfall were found to be positively correlated
      with malaria incidence. INTERPRETATION & CONCLUSION: Our findings showed that A.
      fluviatilis and A. stephensi played a significant role in transmission of malaria
      in Kalsi area of Dehradun.

PMID- 16575115
TI  - Mycological profile of infectious Keratitis from Delhi.
AB  - BACKGROUND & OBJECTIVE: Corneal blindness is a major health problem worldwide and
      infectious keratitis is one of the predominant causes. The incidence of fungal
      keratitis has increased over the last few years. Though a few studies have been
      carried out on mycotic keratitis from north and other parts of India, there are
      none from Delhi. Keeping this in mind, this study was conducted to evaluate the
      frequency of positive fungal cultures in infectious keratitis and of the various
      fungal species identified as aetiologic agents in patients attending a tertiary
      care hospital in East Delhi. METHODS: Corneal scrapings from 346 patients of
      corneal ulcer with suspected fungal aetiology were subjected to direct
      examination by 10 per cent KOH mount, Gram stain and culture. The results were
      examined retrospectively and analyzed. RESULTS: Of the 346 patients of corneal
      ulcer investigated, in 77 (22.25%) cases fungal aetiology was identified. Males
      were more commonly affected and were mostly in the age group of 31-40 yr. It was
      seen that trauma was the most common predisposing factor especially in the
      agriculturists and the farmers. Aspergillus flavus was the most common fungus
      isolated in 31.16 per cent cases, followed by A. fumigatus (16.88%) and Fusarium
      spp. (7.79%). Yeasts were also isolated in 21.62 per cent cases. Both yeasts and
      mycelial fungi were isolated in 6.5 per cent of cases. INTERPRETATION &
      CONCLUSION: Because of serious consequences of infectious keratitis, it is
      important to know the exact aetiology of corneal ulcer to institute appropriate
      therapy in time. Laboratory confirmation should be undertaken and fungal
      infection should be ruled out before prescribing corticosteroids and
      antibacterial antibiotics.

PMID- 16575116
TI  - Detection of Mycobacterium avium & M. tuberculosis from human sputum cultures by
      PCR-RFLP analysis of hsp65 gene & pncA PCR.
AB  - BACKGROUND & OBJECTIVE: Identification of mycobacteria by conventional methods is
      slow, labour intensive and may at times fail to produce precise results.
      Molecular techniques developed in the recent past, overcome these disadvantages
      facilitating rapid identification of most species. We undertook this study to
      characterize mycobacteria isolated from sputa of human patients suspected to have
      tuberculosis by conventional methods and later, by polymerase chain reaction
      restriction fragment length polymorphism analysis (PRA) of hsp65 gene and pncA
      PCR. METHODS: Twenty two mycobacteria isolated from 30 sputum samples were
      identified based on growth rate, pigmentation, cultural and biochemical
      properties and subjected to PRA of hsp65 gene involving amplification of hsp65
      gene and digestion of the product with BstEII and HaeIII in separate reactions
      and analysis of digests by 3 per cent agarose gel electrophoresis. The
      mycobacteria were simultaneously evaluated by M. tuberculosis-specific and M.
      bovis-specific pncA PCR assays in separate reactions. RESULTS: With the
      conventional biochemical tests, the 22 sputum culture isolates were identified as
      M. tuberculosis (19) and M. avium complex (MAC) (3). PCR of hsp65 gene yielded
      439 bp product in all the mycobacteria tested. The RFLP patterns of three MAC
      isolates with BstEII and HaeIII were identical to reference M. avium strain with
      two fragments in each of the digest. M. intracellulare reference strain showed a
      distinct pattern with 3 fragments each in both enzyme digests. The PRA of hsp65
      confirmed MAC isolates as M. avium. M. tuberculosis isolates including H37Rv and
      M. bovis strains could not be discriminated by PRA of hsp65. The two pncA PCR
      assays (M. bovis-specific and M. tuberculosis-specific) detected specifically the
      respective organisms with an amplification product of 185 bp. The MAC strains
      yielded no amplification product in both the pncA PCR assays. INTERPRETATION &
      CONCLUSION: PRA profiles of hsp65 could differentiate MAC isolates into M. avium
      and M. intracellulare but could not distinguish between M. tuberculosis and M.
      bovis. pncA PCR assays were found specific in detecting the respective
      mycobacterial species. The study confirms utility of pncA PCR assays in
      differential identification of M. tuberculosis and M. bovis and that of PRA of
      hsp65 in the identification of M. avium.

PMID- 16575117
TI  - Filiform papillae in the mucosa of the human vaginal wall.
AB  - BACKGROUND & OBJECTIVE: While giving the gross anatomy of the mucosa of the
      vagina, textbooks of Anatomy and Obstetrics and Gynaecology describe the presence
      of a median longitudinal ridge on its anterior wall (columna rugarum anterior)
      and another similar ridge (columna rugarum posterior) on its posterior wall is
      described, and transverse rugae separated by sulci of variable depth, extend
      bilaterally from these ridges. While conducting autopsy of female cases the
      routine examination of vaginal mucosa did not show the presence of longitudinal
      ridges. In addition, some small areas bearing filiform papillae were seen in the
      lower third of the vagina in young subjects. As these papillae have not been
      described earlier, it was decided to study them in detail using scanning electron
      microscopy. METHODS: A total of 215 vaginal specimens were studied. At autopsy
      the vagina was slit open on the lateral sides up to the upper ends of the lateral
      fornices. The anterior vaginal wall was turned up over the uterus and mucosa of
      both walls examined macroscopically. In 16 subjects, small pieces of vaginal
      mucosa bearing filiform papillae were cut out and processed for examination under
      scanning electron microscope (SEM) and a light microscope. In addition, vaginae
      of 55 married women (20-40 yr age) with complain of lower abdominal pain or
      infertility were examined particularly for the median longitudinal ridges on the
      vaginal walls. RESULTS: At autopsy, the two median longitudinal ridges were not
      seen in any instance. Small variable areas of the lower third of the vagina
      showed the presence of filiform papillae on the two walls and at sides; they were
      prominent in the young individuals and tended to become absent in multipara and
      in old age. They were 2 to 3 in number on each wall. Histologically the papilla
      showed a core of highly vascular connective tissue covered by non-keratinized
      squamous epithelium. Immunoperoxidase staining with S-100 showed a large number
      of small nerve fibres in the subepithelial tissue which seemed to be more than in
      the surrounding areas not covered with papillae. INTERPRETATION & CONCLUSION:
      Anterior and posterior median longitudinal ridges were not seen on the vaginal
      mucosa in the autopsy specimens. In all autopsy specimens of young subjects
      between the ages of 15 and 40 yr, variable areas bearing filiform papillae were
      observed on the mucosa of the lower third of the vagina. Further studies need to
      be done to throw light on the role of these papillae.

PMID- 16575118
TI  - Seroprevalence of hepatitis C virus (HCV) in health care workers of a tertiary
      care centre in New Delhi.
AB  - Hepatitis C virus (HCV) is a parenterally transmitted virus that poses an
      occupational hazard to the health care workers (HCWs). No significant data are
      available regarding the prevalence of HCV in health care workers in India. The
      present study was designed to determine the seroprevalence of HCV infection in
      health care workers in a tertiary care centre in New Delhi. The subjects (n=100)
      were divided according to the duration of employment and the unit where they were
      working. Blood samples were collected from all the subjects and sera were tested
      for anti-HCV antibodies. The seroprevalence of anti-HCV was found to be 4 per
      cent. The duration of occupational exposure was not a significant risk factor for
      HCV infection and prevalence of anti-HCV antibodies were highest in HCWs working
      in haemodialysis units. The seroprevalence of HCV in health care workers was
      considerably higher than that reported in the general population, and needs to be
      evaluated on a larger sample.

PMID- 16575119
TI  - Aspergillus fumigatus, Pneumocystis jiroveci, Klebsiella pneumoniae & Mycoplasma
      fermentans co-infection in a HIV infected patient with respiratory conditions
      from Southern India.

PMID- 16575120
TI  - [In vitro effects of cAMP- and cGMP-stimulating drugs on the relaxation of the
      prostate smooth muscle tissue contraction induced by endothelin-1].
AB  - Results from experimental studies suggested a significance of the nitric oxide
      (NO)-cGMP- and cAMP-pathways in the control of the function of the smooth
      musculature of the human prostate. In addition, it has also been assumed that the
      vasoconstrictory peptide endothelin-1(ET-1) may play a role in the dynamic
      component of benign prostatic hyperplasia (BPH) and the so-called lower urinary
      tract symptomatology (LUTS). Nevertheless, up till now, little is known as to
      potential interactions between the contraction of prostatic smooth muscle
      mediated by ET-1 and the relaxation induced by NO and cGMP. Thus, it was the aim
      of the study to elucidate the effects of drugs interfering with the cGMP-pathway
      on the tension induced by ET-1 of isolated human prostate tissue, as well as
      contractile responses of isolated strip preparations to ET-1 and angiotensin-II
      (AT-II). Macroscopically normal human prostate tissue from the transition zone
      was obtained from male patients who had undergone surgery for localized cancer of
      the prostate or urinary bladder. Using the organ bath technique, the ability of
      ET-1 and AT-II to contract isolated prostate strips was evaluated. In another set
      up, the effects of the NO-donor S-nitrosogluthatione (GSNO) and C-type
      natriuretic peptide(CNP), known as an endogenous ligand of the membrane bound
      guanylyl cyclase, (1 nM-1/10 microM) on the tension induced by 0.1 microM ET-1 of
      human prostate strips were investigated. The adenylyl cyclase stimulating agents
      forskolin and NO-donor natrium nitroprusside (NNP) were used as reference
      compounds. While AT-II failed to contract the prostate tissue, ET-1 induced
      stable and reproducible contractions of the tissue strips. The tension induced by
      0.1 microM ET-1 was dose-dependently reversed by the drugs. The rank order of
      efficacy was forskolin >NNP>CNP(1 microM)>GSNO. R(max) values ranged from 55%
      (forskolin) to 35% (GSNO). Forskolin was the only compound which reached an EC50
      value. Our results demonstrate that drugs in terfering with the cGMP- and cAMP
      pathways can reverse the tension induced by ET-1. These findings are in support
      of the hypothesis that both cGMP and cAMP contribute to the control of the
      prostate smooth muscle tension and may provide new strategies for the future
      pharmacotherapy of LUTS und BPH.

PMID- 16575121
TI  - Role of TGF-beta in pathogenesis of diabetic nephropathy.
AB  - Diabetic nephropathy, a major long-term complication of diabetes mellitus is
      characterized by hypertrophy of the glomerular and tubuloepithelial structures
      and thickening of glomerular and tubular basement membranes and progressive
      accumulation of extracellular matrix proteins (fibronectin, collagens and
      laminin) in the mesangium and the interstitium. A host of mediators, such as
      hyperglycemia, glycosylated proteins, systemic and glomerular hypertension,
      proteinuria, growth factors, and cytokines have been implicated in the
      pathogenesis of diabetic nephropathy. Of these, the cytokine transforming growth
      factor (TGF-beta) has emerged as having a key role in the development of renal
      hypertrophy and accumulation of extracellular matrix in diabetes. TGF-beta is
      known to have powerful fibrogenic actions resulting from both stimulation of
      matrix synthesis and inhibition of matrix degradation.

PMID- 16575122
TI  - [Individualization of immunosuppressive treatment in patients with HCV infection
      after transplantation].
AB  - The number of patients with HCV infection is increasing in Georgia. High number
      of infection is noticeable in patients on hemodialysis. 60-70% of them needs
      renal transplantation. This makes the problem more acute especially among the
      organ recipients with HCV infection, who are receiving immunosuppressive
      treatment. The aim of the survey was to work out optimal protocol of
      immunosuppressive treatment for patients after renal transplantation. There were
      clinically observed 39 patients after renal transplantation. They were divided
      into four groups according to the clinical data (serology, replication of HCV and
      different schemes of immunosuppressive treatment). It was shown that
      immunosuppressive treatment carried out among patients with HCV infection after
      transplantation is effective and safe. Consideration of the data leads us to the
      statement that there is no risk of losing transplanted organ in case of
      individualization and minimization of immunosuppressive treatment. Periodic
      control of blood HCV RNA is reasonable during the pre and post operation period.

PMID- 16575123
TI  - [Androgen insensitivity syndrome in adolescents].
AB  - 21 patients aged 16-20 with the kariotype 46, XY were studied. In 20 cases
      complete androgen insensitivity syndrome was diagnosed. All patients had normal
      female appearance and psychosexuality, well-developed breasts, sparse pubic and
      auxiliary hair, normal female external genitalia and short pseudovagina. In 15
      patients unilateral (3) and bilateral (7) herniotomy in their childhood was
      described. Ultrasound examination in all cases revealed the absence of uterus. In
      14 patients gonads were visualized in the pelvic area, unilaterally or
      bilaterally. In one patient with the kariotype 46, XY and following clinical
      characteristics: masculine build, normal female like pubic hair and
      psychosexuality, clitoromegaly, slightly developed breast and pseudovagina,
      incomplete androgen insensitivity syndrome was diagnosed. In all cases of
      complete androgen insensitivity syndrome after finishing puberty gonadectomy
      procedure was carried out, with a subsequent estrogen replacement therapy.
      Diagnostic of rare genetic pathologies, such as androgen insensitivity syndrome,
      with female phenotype and primary amenorrhea, is very important for avoiding
      developing of gonadoblastoma and the timely therapy.

PMID- 16575124
TI  - [A, M and G immunoglobulins during premature pregnancy].
AB  - Immunological process develops as a result of the failure of mechanisms providing
      the state of conditional tolerance of maternal immune system in regard to
      antigens of feto-placental complex. Immune response is mainly directed towards
      maintenance of internal homeostasis of maternal organism in critical conditions,
      and as a result interruption of pregnancy takes occurs. Development of pregnancy
      leads to more expressed decrease of T-cellular indices, as well as of humoral
      immunity. The state of immunodeficiency increases vulnerability of woman organism
      to damaging agents, what, in its turn, promotes development of immunopathological
      process.

PMID- 16575125
TI  - Pap testing and direct immunofluorescence for Chlamydia trachomatis infection in
      pregnant women.
AB  - The aim of the study was to determine the potential for both Pap testing and
      direct immunofluorescence assay for detection of chlamydia trachomatis infection
      in pregnant women. A total of 351 pregnant women (first to second trimesters; age
      range: 15-30 years) were recruited. The background data relating to social and
      marital status, age, anamnestic data were recorded. Serum samples were tested for
      IgM antibodies specific to Chlamydia trachomatis by ELISA. Cervical Pap smears
      were stained by Papanicolaou and direct immunofluorescence. In the present study
      the overall rate of C. trachomatis infections in pregnant women was 33%. Pap
      testing suggested a diagnosis of chlamydia trachomatis infection in 8.5% of cases
      only, direct fluorescence showed positivity in all patients. The highest
      incidence of unmarried status was recorded in the patients with mixed chlamydial
      infection and trichomoniasis, also with chlamydial monoinfection, rare visits to
      the gynecologists were common in patients with mixed chlamydial infection and
      trichomoniasis, mixed chlamydial and HPV infections, also with chlamydial
      monoinfection, multiple lifetime sex partners were reported by the patients with
      combined chlamydial infection and trichomoniasis, also with chlamydial
      monoinfection. The prevalence of asymptomatic C. trachomatis infection was lower
      in women with mixed non-viral infections. The incidence of pelvic inflammatory
      disease was higher in the patients with mixed chlamydial infection and
      trichomoniasis, mixed chlamydial and HPV infections, and chlamydial
      monoinfection, incidence of spontaneous abortions was higher in the patients with
      mixed chlamydial and HSV infections, also with chlamydial monoinfection,
      incidence of ectopic pregnancy was higher in the patients with mixed chlamydial
      infection and trichomoniasis, also with mixed chlamydial and HPV infections.
      Chlamydial infection including cervicitis was frequently diagnosed in women with
      mixed chlamydial and HSV infections, also with chlamydial monoinfection.

PMID- 16575126
TI  - [Concentrational changes of mannose-binding proteins in blood plasma during
      noncomplicated pregnancy and in blood plasma of pregnant women with some
      infections].
AB  - Value of mannose-binding proteins was determined in plasma of pregnant women with
      no complications and also in pregnant women with some infections using affinitive
      chromatography. It was found that the concentration of mannose-binding proteins
      in blood plasma of women equals 0.152+/-0.025 mg/ml. The concentration of mannose
      binding proteins in blood plasma increase during the consecutive trimesters of
      noncomplicated pregnancy. In the first trimester it equals 0.198+/-0.032 mg/ml,
      in the second 0.257+/-0.027 mg/ml and in the third trimester 0.345+/-0.034 mg/ml.
      We also found that the concentration of mannose-binding proteins in blood plasma
      of pregnant woman suffering with chlamydial infection equals 1.025+/-0.115 mg/ml,
      and in blood plasma of pregnant woman suffering with cytomegalovirus infection
      1.278+/-0.144 mg/ml. The obtained data confirm a hypothesis of increased activity
      of innate immune system during pregnancy. Also according to this results
      complications accompanied by chlamydial and cytomegalovirus infections during
      pregnancy is the result of increasing activity of mannose-binding proteins.

PMID- 16575127
TI  - Cell adhesion and apoptosis in ovarian stromal hyperplasia and hyperthecosis.
AB  - The aim of our study was to investigate cell adhesion and apoptosis in ovarian
      stromal hyperplasia and hyperthecosis in reproductive women with and without
      polycystic ovarian disease. We have studied 104 patients with a histological
      diagnosis of ovarian stromal hyperthecosis and stromal hyperplasia. Paraffin
      sections were stained by hematoxylin-eosin, von Gieson and immunohistochemistry
      for Bcl-2 (anti-apoptotic protein) and E-cadherin (cell adhesion marker). We
      assessed the number of Bcl-2-positive and E-cadherin-positive cells. The patients
      were divided into 4 groups: group 1-33 patients with polycystic ovarian disease
      and coexistent stromal hyperthecosis, group 2-28 patients with polycystic ovarian
      disease and coexistent stromal hyperplasia, group 3-24 patients with ovarian
      stromal hyperthecosis, group 4-19 patients with ovarian stromal hyperplasia. Our
      results suggest that in ovarian stromal hyperthecosis and stromal hyperplasia
      coexistent with polycystic ovarian disease, E-cadherin-positivity in internal and
      external theca cells, and granulosa cells is associated with Bcl-2 expression.
      Therefore, ovarian cells expressing Bcl-2 and maintaining E-cadherin-positivity
      may be the viable cells that escape the apoptotic process. In ovarian stromal
      hyperthecosis without polycystic ovarian disease, luteinized stromal cells are
      potentially resistant to apoptosis as they are positive for Bcl-2. In ovarian
      stromal hyperplasia without polycystic ovarian disease, hyperplastic stromal
      cells are potentially susceptible to apoptosis as they are negative for Bcl-2. E
      cadherin is negative both in stromal hyperthecosis and hyperplasia suggesting
      that E-cadherin expression in ovary is limited to granulosa and theca cells only.
      Described characteristics of cell adhesion and apoptosis may play a role in
      pathogenesis of ovarian stromal hyperthecosis and stromal hyperplasia with and
      without polycystic ovarian disease.

PMID- 16575128
TI  - [Neuroprotective treatment of patients with normal tension glaucoma].
AB  - We used antiischemic cardiovascular preparation mildronat as neuroprotective and
      cytoprotective therapy to treat and prevent glaucomatous optic neuropathy.
      Prescription of mildronat was given to 35 patients. From 35 patients 20 were
      women and 15 men, at the age 40-75, visual acuity 0.1-1.0, Pt=18-24, treatment
      course 2,5-3 months. Before and after treatment patients were observed with
      routine methods (visometry, tonometry, determinig visual field on goldman
      spheroperymeter) and besides that on automated static perimetry Humphrey (30-2;
      24-2; Armally) and Medmont studio (Glaucoma test; Full test). Also we used method
      of biomicroophtalmoscopy by positive lens +83 dptr on slit lamp and described
      optic nerve head with our scheme. According to the subjective and objective data
      positive dynamics were signed in 34 patients (63 eyes), negative dynamics in 1
      patient (2 eyes). Glaucoma is medical and social problem in many countries. With
      the difference of expensive methods in prevention and treatment of glaucomatous
      optic neuropathy, using a mildronat as neuroprotective and cytoprotective drug is
      available for the majority of glaucoma patients. We recommend using mildronat in
      patients with primary open angle glaucoma with normolised intraocular pressure
      and in patients with normal tension glaucoma.

PMID- 16575129
TI  - [Dynamics of paranasal sinus and tympanic membrane changes in prolongely
      intubated patients].
AB  - 67 prolongely intubated patients from intensive care unit were under our
      observation. Were performed ultrasound examination and CT scan of paranasal
      sinuses in prolongely intubated patients. In the same patients it was performed
      the examination of tympanic cavity by acoustic impendansometry. Also was
      performed bacteriologic examination of nasal discharge in prolongely intubated
      patients. Our investigations showed, that in prolongely intubated patients there
      is a high risk of development of polysinusitis and evstachitis, which can lead to
      so called fever of unknown origin and even to chronic sepsis. According to the
      authors, sanitation of nasal cavity must be performed every day at least 1 time,
      and if there is the shade--at least 2 times every day. To create the negative
      pressure, it is rational to use iamic--catheter and, through which activation of
      mucocilliary transport is performed. Changing of nasogastral probe is rational
      after one day by turns in each nasal pass. It is rational to cleanse places of
      pressing of these probes with the antiseptic solutions.

PMID- 16575130
TI  - [Characteristic changes of skin and its accessories in type 2 diabetes mellitus].
AB  - The different changes are seen on skin and it's accessories in Diabetes Mellitus,
      some of which represent the prognostic indicator of complicated diabetes and some
      directly contribute in development of them. Numerous problems concerned with the
      diabetic foot could be avoided due to early detection and treatment of these
      changes. The objective data on foot examination of 195 patient with Type 2
      Diabetes Mellitus were analyzed considering the grade of severity of Diabetic
      Peripheral Neuropathy (DPN). It was revealed that the skin humidity is dependent
      on DPN, particularly, the DPN 2-4 times raises the dryness of the skin on the
      foot; the risk of callus development is significantly high in case of painless
      and complicated DPN, accordingly, the possibility of neuropathy ulcer is also
      high in this group. The high incidence of onychomycosis and Yellow nails syndrome
      was noted, accordingly in 28.7% and 39.4% of cases; the Melin's shin spots were
      found in fourth of the patients, mainly in men; a few cases of rubeosis plantarum
      and bulbosis diabeticorum were revealed; the cases of necrobiosis were not noted.
      Thus, the prevalence of the characteristic changes of skin and it's accessories
      in Type 2 Diabetes Mellitus is sufficiently high and it depends on the severity
      of DPN, using early detection of them may avoid many problems related to diabetic
      foot and its complications.

PMID- 16575131
TI  - Color Doppler ultrasonography study of highly qualified wrestler and football
      players upper and lower extremity arteries.
AB  - Reaching high results in sports is main problem in the field of modern sport. It
      is based on sportsman's appropriate health condition to meet high intensity and
      amount of training and competition load. Highly qualified sportsmen wrestlers (30
      individuals) and football players (25 individuals) were studied. Age range was 18
      25 years. The aim was to study upper and lower extremity artery functional
      condition during rest and physical exercise among highly qualified wrestlers and
      footballers. Colour duplex sonography was performed by apparatus Acuson 128 x
      P/10, transducers -7.5 MHz lineal. Upper and lower extremity arteries
      simultaneous visual examination was performed in B-regime with blood stream
      colour cartogram and blood stream spectral analysis. Upper and lower extremity
      artery colour duplex sonography study revealed that wrestlers' upper extremity
      artery lumen diameter and blood stream flow was 1 fold increased. Study also
      demonstrates lower extremity middle calibre artery lumen diameter 1.5 fold
      increase after exercise in football players than in wrestlers. Thus, upper and
      lower extremity arteries differently react on physical exercise among sportsmen
      of different kinds, e.g. footballer lower extremity artery diameter and blood
      flow reach high levels more than in wrestlers, while, the same parameters in
      upper extremities arteries do so in wrestles, rather than in footballers.

PMID- 16575132
TI  - [Effects of metabolic triad (25% polarizing solution, mildronat, preductal MR) in
      acute myocardial infarction].
AB  - The aim of the work was to study the effect of metabolic triad with different
      mechanisms of acting--high-dose Glucose-Insulin-Potassium--25% polarizing
      solution (25% glucose, 50 IU soluble insulin and 4% 144 ml KCL-GIK), mildronat,
      preductal MR on the functional condition of heart during the acute myocardial
      infarction. 20 patients from the main group and 20 from the control one have been
      under the study. Patients with diabetes and heavy forms of heart failure (killip
      class>2) were not included in the study. Evaluation of the functional condition
      of heart was based on ECG and echocardiography data received before and after the
      treatment. It was determined that the frequency of the rhythm disorder decreases
      in the conditions of metabolic triad as well as during the thrombolitic
      reperfusion. Average period of time for normalization of S-T segment elevation
      made up 5.4+/-1.8 days and 7.3+/-1.2 days in case of the control group. The
      received data make it relevant to include the complex metabolic triad for
      preventive purpose during the complications followed after the acute myocardial
      infarction.

PMID- 16575133
TI  - [Neuropsychiatric aspects of diagnostics of nonepileptic seizures].
AB  - The outcome of nonepileptic seizures (NES) is usually poor. The early recognition
      suggests better prognosis. This study is undertaken to examine the value of
      neuropsychiatric method for making accurate diagnosis of the psychiatric disorder
      that underlies psychogenic NES. Multidisciplinary approach to clinical assessment
      of such patients with chronic or resistant course of seizure disorder was used.
      Out of 6 patients, who went through the neuropsychiatric evaluation, two were
      admitted with a diagnosis of status epilepticus, three--with acute episodes of
      repetitive seizures and one--with diagnoses of bettolepsy. The results
      demonstrated that in four cases seizures were the manifestation of dissociative
      disorder (F 44), in one--of somatic form autonomic dysfunction (F 45.3) and the
      last patient had delirium due to epilepsy. All of the four patients with the past
      history of epilepsy were treated with antiepileptic drugs (AED). In two cases
      diagnosis of epilepsy and AED therapy were withdrawn. In the remaining cases we
      supposed the coexistence of epilepsy and NES. Our data suggests that
      incorporating of neuropsychiatric methods into the diagnostic battery for people
      with suspected and/or intractable epilepsy help in distinguishing NES and
      epilepsy as well as in revealing the underlying psychic disorder, which leads to
      formulation specific treatment program.

PMID- 16575134
TI  - An expert system for differential diagnosis of tall stature syndrome.
AB  - There was created medical expert system for differential diagnosis of disorders
      and diseases manifested by tall stature. They were selected based on the
      information provided by two major computer databases, LDDB [London Dysmorphology
      Database] and Orphanet. Clinical signs, i.e. diagnostic criteria were developed
      according to 7 experts: manuals and textbooks, computer databases and online
      resources in pediatrics and rare diseases. Linguistic terms expressing the
      frequency and/or probability of presence of various symptoms were matched to
      numerical equivalents. The data from different experts were summarized according
      to the expertons' method and the inference engine was based on the Bayes theorem.
      An interface was made up by a set of slides with questions accompanied by boxes
      beside and user is expected to check corresponding boxes. The program was created
      in Borland C++ Builder. After having processed the entered data, the expert
      system produces the most probable five diagnostic possibilities and ranks them in
      order of likelihood.

PMID- 16575135
TI  - Non-viral wheezing in preschool children: the effect of inhaled fluticasone on
      symptoms and lung function.
AB  - Aims of this study were: to evaluate changes in lung function in wheezing
      children with detected MP and CP infection according to treatment; to measure the
      response to inhaled corticosteroids in children with significant wheezing who
      were selected as having a high risk of progressing into childhood asthma. 54
      children were randomly assigned 2:1 into 2 groups-the main group (36 patients),
      in which inhaled corticosteroids were administered, and the control group (18
      patients), without inhaled corticosteroids. Serum IgE levels were determined
      using the ELISA (reagents: IBL-Hamburg). Serologic studies were performed by the
      ELISA for IgM and IgG antibodies to MP and for IgG and IgA antibodies to CP
      (reagents: ImmunoLISA, Orgenics, Israel) on the Hiperion MRIII (USA). Pulmonary
      function testing was done with SpiroLab II (DEGO GmbH, Medizin-Elektronik,
      Germany). The patients of both groups were administered macrolides: azitromycin
      during five days. Patients of the first group received inhaled fluticasone
      propionate 125 mg twice daily. The parents were asked to record symptoms. Each
      symptom (wheezing, cough, and shortness of breath) were scored on a scale of 0 to
      3--daily symptom score (DSS). Scores were calculated every 4 weeks for a total
      treatment period 16 weeks. The days within each period on which the DSS equalled
      zero were pointed as symptom free days (SFD). It had been shown an significant
      improvement in DSS, an increase in SFD and significant improvement of the lung
      functions following the treatment with inhaled fluticasone and macrolide in
      children with wheezing and documented MP or CP infection, compared to control
      group treated only with antibiotics. In conclusion, the use of ICS should be
      seriously considered in children with wheezing and the risk of persisting
      symptoms.

PMID- 16575136
TI  - [Influence of bisphosphonate treatment on the radiological features of
      osteogenesis imperfecta in children].
AB  - The Osteogenesis imperfecta (OI) is a hereditary disturbance of collagen
      biosynthesis. The illness is characterized by frequent fractures that
      consequently cause functional disturbance of locomotion system as well as
      deformation of long tubular bones. The purpose of the present work was to study
      radiological features of clinical forms of osteogenesis imperfecta during
      bisphosphonate treatment in children according to the schemes we developed taking
      into consideration the type of illness and the age of the patient. The total
      number of 32 patients, aged 1-15, suffering from osteogenesis imperfecta, have
      been investigated. The patients have been divided into three groups depending on
      the type of illness (I, III and IV type). Type II (lethal form) has not been
      observed by us. All patients, participating in the study underwent radiological
      examination of tubular bones and vertebra pre and post treatment. The results of
      the study showed that bisphosphonate treatment has positive effects in patients
      of type I and IV of osteogenesis imperfecta and is less effective in the type III
      of the diseases.

PMID- 16575137
TI  - [Comparison of PIM and SOFA scoring systems for mortality risk prognosis in
      critically ill children with sepsis].
AB  - The task of the study was the comparison of 2 scoring systems SOFA and PIM for
      mortality risk assessment in intensive care units. SOFA score is evaluated on
      admission and thereafter 72 and 120 h until ICU discharge in Children's Central
      Clinical Hospital from 2001 to 2005 years. Total 200 patients were studied. Mean
      age was 234.5+/-14.5. Mortality rate was 54 (27%). 89 (44.5%) were females and
      111 (55.5%) were mails. Mechanical ventilation was performed in 72 (36%)
      patients. Septic shock was developed in 39 (19.5%) cases. Diagnose was confirmed
      by bacteriology in 68 (34%) cases. Higher score was in 93 (46.5%) cases, middle
      scores in 94 (47%) cases and low in 13 (6.5%) cases at the first day of
      admission. After 72 h. higher score was in 33 (16.5%) cases, middle in 113
      (56.5%) cases and low in 54 (27.5%) cases. By evaluation with PIM--Higher score
      was in 58 (29%) cases, middle scores in 51 (25.5%) cases and low in 91 (45.5%)
      cases at the first day of admission. There is a correlation between the SOFA and
      PIM scores and paediatric mortality. Sofa scores predict mortality in ICU better
      then PIM scoring system. Kendall's tau of SOFA 0.64+/-0.3. Kendall's tau of PIM
      0.45+/-0.2. Sofa scores is an excellent tool to describe the extent of organ
      dysfunction in critically ill patients.

PMID- 16575138
TI  - [Epidemiology, clinical picture, prevention and treatment of Avian influenza].
AB  - Current data concerning epidemiology, clinical picture, pathogenesis, prevention
      and treatment of Avian influenza H5N1, data of pharmacodynamics and
      pharmacokinetics of antiviral drugs--neuraminidase inhibitors and M2 channels
      inhibitors, also the recommendation of WHO for prevention prevalence of infection
      were discussed in the review. Strategic measures of WHO aims to protect humans
      from contact with infected poultry, in case of contact, to prevent transmission
      of this infection from human to human and occurrence of pandemic. Infected birds
      were the major source of the H5N1 influenza virus among humans in Asia. Mainly
      humans became infected by eating infected birds, by poor hygiene procedures when
      cooking infected birds, or by close contact with infected poultry. At present
      transmission of the H5N1 influenza from human to human by aerosol way hasn't been
      registered, but ongoing monitoring for identification mutation and adaptation of
      H5N1 influenza virus to human is needed. Season influenza and avian H5N1
      influenza differ by the ways of transmission, clinical picture, severity,
      pathogenesis, response to treatment. Diagnostic of infection is difficult due to
      non-specific initial symptoms, in most cases disease begins with disturbance of
      under respiratory ways and in rare cases--from upper respiratory ways. High viral
      titre is identified in pharynx but not in nose. Initial symptoms of the H5N1
      influenza are: fever greater then 38 degrees Celsius, mild cold, cough and
      shortness of breath, practically all patient have viral pneumonia, later
      secondary bacterial infection occurs, mild to severe respiratory distress,
      diarrhea, vomiting and abdominal pain. Conjunctivitis is rarely diagnosed
      contrary to season influenza. Sometimes gastrointestinal disorder begins a week
      early then respiratory symptoms. Complication also includes renal and multi organ
      failure. The cytokine storm is commonly developed during H5N1 influenza. For
      treatment and for prevention (under certain conditions) of the H5N1 influenza
      neuraminidase inhibitors such as oseltamivir (Tamiflu) and zanamivir (Relenza)
      are recommended. Currently circulatory of the H5N1 strains are fully resistant to
      an older class of antiviral drugs--the M2 channels inhibitors (amantadine and
      rimantadine). The knowledge of epidemiology, pathogenesis, clinical picture,
      treatment of the H5N1 influenza in humans, in spite of progress isn't complete.
      Future coordination of scientific investigation of the H5N1 influenza in humans
      should be provided not only in the countries where infection was revealed, but
      all around the world.

PMID- 16575139
TI  - [Risk factors of the development of allergic diseases in children at the junction
      of XX-XXI centuries].
AB  - Analysis of the scientific achievements of Allergology, Immunology, Genetics and
      Profpathology as well as scientific investigation the authors set categories of
      causes, characteristics and promoting factors, that cause progressive increase of
      allergic diseases and atopy in children. Allergic heredity plays significant role
      in the incidence of allergic diseases among children. The focus is made on
      development of toxicosis during the pregnancy, frequency of abortions, smoking
      and treatment with drugs during pregnancy and lactation, excessive consumption of
      cow milk during lactation. Numerous evidences confirm the negative role of high
      environmental pollution that is observed during the last decade in the increase
      of allergoses. Besides, it is worth mentioning that food and plant allergens
      greatly contribute in the development of allergens in children. Special attention
      should be paid to the parents' professional activities in antenatal period of the
      fetus development, particularly, to their professional contacts with the
      industrial allergens. Three constitutional types of children are discussed, based
      on them it is possible to make projections about development of different types
      of allergoses in children. The role of different chemical. biological and
      physical air pollutants is indicated in setting allergic status in children.
      Conclusions made on the basis of the analysis of the existing information will
      help researchers and practicing physicians to prevent development allergic
      pathologies in children in antenatal period and later progressive of manifested
      disease by means of purposive, effective preventive measures and treatment
      complexes.

PMID- 16575140
TI  - [Influence of phenol on biochemical and morphological indices of blood in rats].
AB  - Influence of different doses of phenol on some biological and morphological
      indices of rat blood was studied. It has been established that glucose and total
      protein concentration decreased, but beta-lipoprotein concentration increased in
      response to intraperitoneal injection of xenobiotic. The morphological study of
      structural indices of blood formed elements has demonstrated that intensively of
      the defensive response of blood formed elements was phenol dose-dependent. It has
      been established that major concentration of above-mentioned xenobiotic generate
      destruction of blood formed elements.

PMID- 16575141
TI  - [Disorders of liver oxidative metabolism during experimental obesity].
AB  - Evidence of cause-and-effect relation between obesity and severe metabolic
      disorders, including damages of lipid exchanges and liver metabolism, indicate to
      the significance of this problem for current medicine. Obesity alters adipose
      tissue metabolic and endocrine function and leads to an increased release of free
      fatty acids, that contribute to the obesity associated complications. The aim of
      our study was the investigate liver oxidative metabolism disorders during obesity
      and appreciation of possibility of correction of this disorders by green tea
      katechins. During experiments decreasing of intensity of electron transport chain
      in liver mitochondria has been revealed. That increases possibility of uncoupled
      electrons leakage and formation of superoxyde radicals. Chronic production of
      reactive oxygen species during obesity promotes the intensification of free
      radical processes, developing of oxidative stress and appears by lipoperoxil
      radical's formation in liver. That indicates to the changes of membrane'
      selectively permeability and homeostasis disorders in liver. Under the influence
      of green tea catechizes the mitochondrial and microsome electron transport chain
      disorders restores and intensity of peroxidation decreases.

PMID- 16575142
TI  - [Dynamics of Trazodone adsorption on the surface of erythrocytes].
AB  - The pharmacokinetics and pharmacodynamics of Trazodone were investigated by HPLC
      chromatography in the blood plasma and in the erythrocyte supernatant. Two groups
      of samples (plasma and supernatant) were monitored. The drug was administered to
      adult dogs and the blood samples were collected for further analysis following
      10, 20, 60 min. and 4.0; 6.0 and 8.0 hours since the injection. Metabolism of
      dopamine and homovanilic acid is closely dependent on the pharmacokinetic of
      Trazodone. Concentration of homovanilic acid in the blood and supernatant is
      synchronized with the course of pharmacokinetics of psychotropic preparation.
      Pharmacokinetic and pharmacodynamic approaches were used in the experiments.
      Effective action of psychotropic drugs is impossible without extensive knowledge
      of their pharmacokinetics and pharmacodynamics. They are concerned with the need
      to determine concentration in body fluids. Experimental study was performed in
      the adult dogs. Adsorption dynamics of trazodone on the surface of erythrocytes
      was studied and comparison of the obtained data with the character of
      pharmacokinetics of tradozone in plasma was performed.

PMID- 16575143
TI  - [HLA and endocrine diseases susceptibility in Georgian population].
AB  - A total of 137 patients from the Georgian population were examined, among them: I
      group--30 patients with diabetes mellitus type I, II group--64 patients with
      hyperthyroidism of Grave's disease and III group--43 patients with Cushing's
      disease. Antigens of A, B, C and D loci of the HLA system were determined in all
      patients. HLA DR 3 was determined in 43% patients with diabetes mellitus type 1.
      The relative risk (RR) in carriers of this antigen was 2,7 and HLA DR 4 in 47%
      patients of the same group with RR--4.7. In the group with Grave's disease HLA DR
      3 was determined in 54% of patients, RR in carriers of this antigen was 4.4. In
      patients with Cushing's disease was determined HLA DR 3 and HLA DR 4 antigens
      with RR 3.7. At the same time decrease in the frequency of HLA DR 2 antigen was
      found in all groups of patients. The authors discussed the problem of the
      predisposing role of HLA DR 3 and DR 4 antigens in the development of these
      endocrine diseases in Georgian population and the "protective" role of the HLA DR
      2 antigen.

PMID- 16575144
TI  - [Methemoglobin and osmoresistance of erythrocytes in patients with different
      types of goiter].
AB  - The purpose of this study was to determine the level of methemoglobin in the
      blood and osmoresistance of erythrocytes in patients with different types of
      goiter and control subjects. Investigated parameters indicate to the antioxidant
      status of human organism. We examined 12 healthy controls and 49 hyperthyroid
      patients: 17 patients with nodular goiter (mild thyrotoxicosis), 22 patients with
      diffuse toxic goiter (high level of thyrotoxicosis) and 10--with euthyroid nodule
      goiter. Osmoresistance of erythrocytes was measured by differential
      photoelectrocolorymetric method and methemoglobin--by spectroscopic method. We
      had received significant correlation between the level of methemoglobin,
      osmoresistance of erythrocytes and the degree of thyrotoxicosis. The results once
      again prove sensitivity of antioxidant status in response to toxicity, in
      particular against thyrotoxicosis.

PMID- 16575145
TI  - [The role of oxygen-nitrogen stress in pathogenesis of amoebiasis].
AB  - The goal of present investigation was determining peculiarities of oxidation
      metabolism in the case amoebiasis. The activity of pro- and anti-oxidative
      systems and content of NO in the blood of the patients with abscess, which
      developed in hepatic amoebiasis, has been studied. It was shown that in the
      patients' organism an increased generation of the free radicals of oxygen and
      nitrogen does occur. Intensification of peroxidation of the lipids (POL) and
      inactivation of antioxidation system of the organism were observed as well.
      Intensifying of the oxygen-nitrogen stress in the organism of the patients with
      amoebiasis, is induced by the activated neutrophyls accumulated in the focus of
      injury, which developed during invasion of amoebas. Low efficiency of the
      neutrophyl-induced oxidation explosion in amoebiasis, partly is determined by the
      highly active anti-oxidative system of these parasites. Their sensitivity to NO,
      allows suggesting of implementation of preparations--NO donors and modulators of
      NO production in the host organism, in treatment of the parasitic infections.

PMID- 16575146
TI  - The method of melanocytes isolation.
AB  - To judge the therapeutic value and evaluate the mechanism of action of this
      specific transplantation procedure we have performed an isolation of the
      melanocytes in experiment on the hens. The black hens (n=5), 3-5 kg of body
      weight were used in experimental study. Hens were housed in standard laboratory
      conditions under 12-hr day-night cycles with provision of pelleted diet and water
      ad libitum. All hens received care according to institutional guidelines. Using a
      hand dermatome, a shave biopsy specimen of approximately 2 cm2 was taken from the
      hens' normally pigmented region under local anesthesia (lidocaine hydrochloride,
      20 mg/mL). The wound was covered with a transparent occlusive bandage (4 cm x 4
      cm) and secured with gauze and adhesive tape. The melanocytes suspension have
      been obtained by fermentative digestion.

PMID- 16575147
TI  - Immune status during fracture of lower jaw.
AB  - Immune status during fracture of lower jaw is a very important factor of
      pathogenesis. Immune depression is developing shortly after the trauma and it
      turns out to be a bad prognostic sign, during which the risk of developing the
      bone wound complications and traumatic osteomyelitis increase, and in case of
      absence of such complications we are faced with significant extension of a term
      of healing of bone wounds. We have carried out immune studies in 20 patients with
      lower jaw fractures. To study SlgA and lysozyme activity we took saliva and
      studied percentage of T- and B-lymphocytes (and their sub-populations) in blood
      by the use of micro method. Immunoglobulins were defined by the method of radial
      immuno diffusion; we determined the interferon system by in vitro stimulation of
      leucocytes; neutrophilic phagocyte activity was studied by the method of Kost
      U.A. and Stepko M.I. According to the obtained results, during fractures of lower
      jaw sharp decrease of interferon system and significant decrease of phagocyte
      activity was observed. Likewise was decreased lysozyme and SlgA indices, which
      refer to the depression of immune status of mouth cavity. From the cell immunity
      indices the decrease of T-activators and T-helpers and reduction of
      immunoregulation index should be emphasized. Quantity of B-lymphocytes was
      decreased by 10%. With the practical point of view the obtained results refer,
      alongside with carrying out the surgical, orthopedic and anti-microbial
      treatments, to the urgency of application of activators of phagocytosis,
      interferon and lysozyme immunomodulators. With the view of correction of cell
      immunity it is necessary to correct factors of T-lymphocytes and to increase
      activity of SigA and lysozyme, as the factors determining local resistance. The
      results obtained by us are rather important with the view of both immunology and
      applied, practical medicine. It enables us to lead the substantiated immune
      therapy, which will be harmonized with other etiotropic anti microbial therapy
      and will help us to improve significantly the results of anti-inflammation
      therapy and to decrease cases of purulent complications.

PMID- 16575148
TI  - [Current trends of using evidence based medicine principles in urgent surgical
      service development in Adjara].
AB  - Ongoing social and economic processes in Georgia had a strong influence on the
      basic health indicators of the population. Change of usual lifestyle, poor living
      conditions, worsening of communications and unemployment leads to condition of
      the chronic stress and development of related pathologies. According to the
      current statistics there is a great increase in the cases of surgical pathology.
      Taking into account the existing realities the serious problem is a provision of
      and accessibility to the health services designated for this groups of the
      population. Based on the advanced methods of research the author of the article
      studied in Adjara the social environment, working and living conditions and
      effectiveness of preventive, curative and rehabilitative surgical care rendered
      to the patients with severe surgical pathologies. There have been carried out the
      analysis of the processes, characterising health and medical activities of the
      population of Autonomous Republic. The author believes, that despite the number
      of problems in health system, introduction of well organised primary health care
      will make possible to provide the majority of patients with timely and qualified
      care.

PMID- 16575149
TI  - [Monitoring of level of antibiotic resistance of microbial strains, isolated in
      cases of surgical infections in period from 2003 to 2005 years].
AB  - Microbial structure of surgical infections and level of antibiotic resistance of
      microbial strains isolated in period from 2003 to 2005 years was investigated. As
      a result of performed investigation, 871 strains of different microbial species
      were isolated. It occurred that, in microbial structure of wound infections
      isolation of gram-positive microflora (509 strains) was 1,5 times higher than
      gram-negative (362 strains). Quantitative analisation has shown, that
      microorganisms were isolated in high amount, COU=10(5)-10(8). In 49% of cases
      microorganisms were isolated as microbial associations. In 37% of isolated
      microorganisms they had Nosocomial features. Investigation of sensitivity of
      microorganisms to antibiotics of all known group has shown tendency of rise of
      level of resistance even to modern antibiotics. It was found out Cephalosporins,
      Phtorhinolons and Karbapenems are showing good result. Basing on performed
      investigations could be recommended--strictening of strategy and control in use
      of antibiotics.

PMID- 16575150
TI  - Influence of experimental hyperthyreosis on hepatocytes' cell cycle in white
      mice.
AB  - The thyroid hormones play the essential regulatory role in the process of
      hepatocyte proliferation and polyploidization. T3 has been shown to be a powerful
      inducer of hepatocyte proliferation in the rats. Although T3 is known to have a
      strong mitogenic effect on hepatocytes in vivo, little is known about long-term
      effects of thyroid hormone on liver parenchyma. Here we have studied the effect
      of thyroid hormone on the cell cycle of hepatocytes in white mice during
      experimental hyperthyreosis. The experiments were performed on 74 white mice,
      distributed in three age groups (juveniles, adults, senescents). Experimental
      hyperthyreosis was induced by injections of L-thyroxine (50 mcg/1 kg body
      weight). The method of flow cytometry was used. The results obtained allowed us
      to clarify the predominant role of thyroid hormones in the regulation of
      hepatocyte cell cycle. The significant role of the hyperthyroid status on liver
      polyploidization was evident. However, this effect seems to be age dependent.
      According to our data, hyperthyreosis in juveniles increases the degree of
      ploidity, whereas in adult and senescent mice--decreases. On the other hand,
      under action of hyperthyroid status the amount of apoptotic nuclei decreases in
      juveniles and increases in adults and senescents.

PMID- 16575151
TI  - [Sexual development of children and teenagers in the families deported from
      Abkhazia (dynamic observation)].
AB  - The aim of the study was the evaluation of physical and pubertal development of
      children from the families deported from Abkhazia who were exposed to significant
      psycho-somatic stress and prolonged socio-economical infringement. Dynamic
      observation started in 1998. Children, 9-15 years of age, have been studied. 200
      children have been selected by the individualised methods (115 were girls and 85
      were boys). In parallel children of appropriate age and gender groups from the
      local families have been studied. The investigations were conducted according to
      the generally accepted schemes and tables suggested by Tenner (17), for girls and
      by V.M. Vedenski (8) for boys, respectively. The analysis of obtained results
      showed that the total percent of delayed puberty in studying group was 21.4%
      versus 30.0% in the groups of 1998. Consequently, index of delay in control group
      was equal to 3.9% (2005) and 5.0% (1998). The group, exceeding the norms of
      puberty (accelerates) was 4.8% versus 11.2% in control group in comparison with
      the data of 1998--5.4% versus 15.0%, respectively. It should be concluded that
      due to the obtained results, comparing with the analogic groups of 1998, the
      number of delayed puberty has been reduced by approximately 9.0%. The number of
      cases exceeding the norms of puberty has been decreased slightly.

PMID- 16575153
TI  - Dimethylsphingosine regulates intracellular pH and Ca(2+) in human monocytes.
AB  - Dimethylsphingosine (DMS) was first reported as an inhibitor of protein kinase C
      and later has been used as a specific inhibitor of sphingosine kinase.
      Furthermore, its anti-cancer effect has become a basis for development of
      chemotherapy. Nevertheless, its anti-neoplastic mechanism has poorly been
      understood. In the present study, we observed that DMS increased intracellular pH
      and Ca(2+) concentration in U937 human monocytes. To further characterize these
      DMS-induced actions, we employed structurally-related sphingolipids and specific
      pharmacological tools such as inhibitors of protein kinase C and Na(+)/H(+)
      exchanger and found that the two responses of DMS were mimicked by four
      stereoisomers of sphingosine and two isomers to dihydrosphingosine, but not with
      sphingosine 1-phosphate, sphingosyl-phosphorylcholine, and C2-ceramide.
      Furthermore, DMS-induced pH increase was independent of Na(+)/H(+) exchanger
      activity. We also characterized the interrelationship between DMS-induced pH
      increase and DMS-induced Ca(2+) increase. Since DMS is considered to be a good
      anti-cancer candidate, our characterization of DMS actions provides useful
      information for development of DMS chemotherapy.

PMID- 16575152
TI  - Peripheral antinociception by carbamazepine in an inflammatory mechanical
      hyperalgesia model in the rat: a new target for carbamazepine?
AB  - This study investigated whether carbamazepine could produce local peripheral
      antinociception in a rat model of inflammatory mechanical hyperalgesia, and
      whether adenosine receptors are involved. Carbamazepine (100-1000 nmol/paw) co
      administrated with a pro-inflammatory compound, concanavalin A, into the hind paw
      caused a significant dose- and time-dependent anti-hyperalgesia. Coadministration
      of caffeine (250-1000 nmol/paw), a nonselective adenosine-receptor antagonist, as
      well as DPCPX (10-30 nmol/paw), a selective adenosine A(1)-receptor antagonist,
      with carbamazepine, significantly depressed its anti-hyperalgesic effect. Drugs
      injected into the contralateral hind paw did not produce significant effects.
      These results suggest that carbamazepine produces local peripheral anti
      hyperalgesia via peripheral adenosine A(1) receptors.

PMID- 16575154
TI  - Role of serum myostatin during the lactation period.
AB  - Myostatin, also known as GDF-8 (Growth/Differentiation Factor-8), is a member of
      the TGF-beta superfamily that negatively regulates skeletal muscle mass in
      mammals. Mutation of the myostatin gene in mice, cattle, and humans causes a
      massively developed skeletal muscle, characterized by muscle hypertrophy and
      hyperplasia. Although myostatin is predominantly expressed in skeletal muscle
      tissue, several recent studies have shown the presence of myostatin protein in
      blood and suggested a possible role for circulating myostatin in the regulation
      of skeletal muscle mass. In the present study, we examined changes in the levels
      of active form myostatin (13 kDa) in serum after birth by Western blot analysis
      to predict the role of serum myostatin in early postnatal muscle growth in the
      rat. Interestingly, the amount of active form myostatin in serum increased after
      birth and then decreased along with ageing after weaning. To clarify the role of
      increased serum myostatin during the postnatal period, we administrated
      follistatin, an inhibitor of myostatin activity, into postnatal rats
      intraperitoneally just after birth. Follistatin-administration during the
      postnatal period caused selective hypertrophy of type II muscle fibers in the
      soleus muscle. These results demonstrate that myostatin in serum acts on skeletal
      muscle and negatively regulates early postnatal muscle growth.

PMID- 16575155
TI  - Rabbit oocyte cytoplasm supports development of nuclear transfer embryos derived
      from the somatic cells of the camel and Tibetan antelope.
AB  - This study was designed to examine the ability of rabbit metaphase II oocyte
      cytoplasm to support the development of interspecies nuclear transfer embryos
      reconstructed using donor nuclei from different species. Skin fibroblast cells
      from a camel and Tibetan antelope were used as donor nuclei. As a first step, we
      investigated the efficiency of different activation protocols by comparing the
      parthenogenetic development of rabbit oocytes. The protocol that yielded the
      highest blastocyst rate was used to activate the reconstructed embryos in nuclear
      transfer experiments. In addition, the effect of donor cell serum starvation on
      the development of the reconstructed embryo was also examined. More than half of
      the karyoplast-cytoplast couplets could be fused, and about one third of the
      reconstructed embryos were capable of completing first cleavage, regardless of
      the species of donor nuclei. Some of the cleaving reconstructed embryos were even
      capable of progressing further and developing to the blastocyst stage (1.4-8.7%
      for the Tibetan antelope and 0-7.5% for the camel, respectively). Our results
      suggest that the mechanisms regulating early embryo development may be conserved
      among mammalian species and some factors existing in rabbit oocyte cytoplasm for
      somatic nucleus reprogramming and dedifferentiation may not be species-specific.
      Rabbit oocyte cytoplasm can reprogram donor nuclei regardless of the origin of
      the nucleus and support in vitro development to an advanced stage.

PMID- 16575156
TI  - The continuing quest to comprehend genomic imprinting.
AB  - The discovery of the phenomenon of genomic imprinting in mammals showed that the
      parental genomes are functionally non-equivalent. Considerable advances have
      occurred in the field over the past 20 years, which has resulted in the
      identification and functional analysis of a number of imprinted genes the
      expression of which is determined by their parental origin. These genes belong to
      many diverse categories and they have been shown to regulate growth, complex
      aspects of mammalian physiology and behavior. Many aspects of the mechanism of
      imprinting have also been elucidated. However, the reasons for the evolution of
      genomic imprinting remain enigmatic. Further research is needed to determine if
      there is any relationship between the apparently diverse functions of imprinted
      genes in mammals, and their role in human diseases. It also remains to be seen
      what common features exist amongst the diverse imprinting control elements. The
      mechanisms involved in the erasure and re-establishment of imprints should
      provide deeper insights into epigenetic mechanisms of wide general interest.

PMID- 16575157
TI  - Imprinting today: end of the beginning or beginning of the end?

PMID- 16575158
TI  - Interactions between imprinting effects: summary and review.
AB  - Mice with uniparental disomies (uniparental duplications) for defined regions of
      certain chromosomes, or certain disomies, show a range of developmental
      abnormalities most of which affect growth. These defects can be attributed to
      incorrect dosages of maternal or paternal copies of imprinted genes lying within
      the regions involved. Combinations of certain partial disomies result in
      interactions between the imprinting effects that seemingly independently affect
      foetal and/or placental growth in different ways or modify neonatal and postnatal
      development. The findings are generally in accord with the 'conflict hypothesis'
      for the evolution of genomic imprinting but do not demonstrate common growth axes
      within which imprinted genes may interact. Instead, it would seem that any gene
      that favours embryonic/foetal development, at consequent cost to the mother, will
      have been subject to evolutionary selection for only paternal allele expression.
      Reciprocally, any gene that reduces embryonic/foetal growth to limit disadvantage
      to the mother will have been selected for only maternal allele expression. It is
      concluded that survival of the placenta is core to the evolution of imprinting.

PMID- 16575159
TI  - Complementation hypothesis: the necessity of a monoallelic gene expression
      mechanism in mammalian development.
AB  - Gene expression from both parental alleles (biallelic expression) is beneficial
      in minimizing the occurrence of recessive genetic disorders in diploid organisms.
      However, imprinted genes in mammals display parent of origin-specific monoallelic
      expression. As some imprinted genes play essential roles in mammalian
      development, the reason why mammals adopted the genomic imprinting mechanism has
      been a mystery since its discovery. In this review, based on the recent studies
      on imprinted gene regulation we discuss several advantageous features of a
      monoallelic expression mechanism and the necessity of genomic imprinting in the
      current mammalian developmental system. We further speculate how the present
      genomic imprinting system has been established during mammalian evolution by the
      mechanism of complementation between paternal and maternal genomes under
      evolutionary pressure predicted by the genetic conflict hypothesis.

PMID- 16575160
TI  - Genomic imprinting is a barrier to parthenogenesis in mammals.
AB  - Only mammals have relinquished parthenogenesis as a means of producing
      descendants. Bi-parental reproduction is necessary due to parent-specific
      epigenetic modification of the genome during gametogenesis, which leads to non
      equivalent expression of imprinted genes from the maternal and paternal alleles.
      However, a series of our work showed that alteration of maternal imprinting by
      oocyte reconstruction using non-growing oocytes, together with deletion of the
      H19 gene provide appropriate expression of imprinted genes from the maternal
      genome. The resulting ng (non-growing)/fg (fully-grown) parthenogenic embryos
      were developed to term. Here, we discuss how the parthenogenetic embryos survived
      as normal individuals.

PMID- 16575161
TI  - Origins of extreme sexual dimorphism in genomic imprinting.
AB  - Roughly equal numbers of imprinted genes are subject to repression from alleles
      of maternal and of paternal origin. This masks the strong sexual dimorphism that
      underlies major aspects of imprinted gene regulation. First, imprints are
      established very early in the male germ line and persist for the reproductive
      life of the organism, while maternal genomic imprints are established shortly
      prior to ovulation and are erased soon thereafter in the primordial germ cells of
      the next generation. Second, many CpG island-associated promoters are subject to
      maternal methylation but no known promoters are subject to paternal-specific
      germline methylation. The few known paternal methylation marks are kilobases
      distant from the affected genes and have a low CpG density. Third, Dnmt3L is
      required for imprint establishment but not transposon methylation in female germ
      cells, while Dnmt3L is required for transposon methylation and has only a minor
      role in de novo methylation at imprinted loci in male germ cells. Fourth,
      maternally expressed genes are commonly repressed on the paternal allele by
      paternally expressed imprinted genes produced in cis and encoding nontranslated
      RNAs. It is here suggested that rapid loss of highly mutable methylated CpG sites
      has led to the depletion of methylation target sites in paternally repressed
      imprinted genes, and that an imprinting mechanism based on RNAs or local
      inhibitory influences of ongoing transcription of regulatory loci has evolved to
      counter the erosion of paternally methylated regulatory regions. This mutability
      model is based on the fact that paternally methylated sequences are maintained in
      the methylated state for a much longer time than are maternally methylated
      sequences, and are therefore lost at a correspondingly faster rate. The
      difference in timing of imprint establishment is likely to underlie the
      increasing sexual dimorphism of other aspects of imprinted gene expression.

PMID- 16575162
TI  - Genomic imprinting in the mealybugs.
AB  - The coccid insects (Hemiptera; Sternorrhyncha; Aphidiformes; Coccoidea;
      Pseudococcidae) are well suited to study not only the mechanisms of genomic
      imprinting but also facultative heterochromatization, a phenomenon well
      exemplified by inactivation of the X chromosome in female mammals. Coccids show
      sex-specific heterochromatization of an entire set of chromosomes and
      transcriptional silencing of all the paternally contributed chromosomes in males.
      Thus, genomic imprinting and the resultant differential regulation operate on 50%
      of the genome in contrast to the single X chromosome in female mammals. A
      significant insight into the phenomenon of genomic imprinting has come from very
      elegant cytological analysis of the coccid system. Recently, efforts have been
      made to dissect out at the molecular level the phenomenon of genomic imprinting
      in these insects. The present review summarizes both of these aspects. In light
      of the accruing experimental evidence for chromatin-based differences in the
      maternal and paternal genomes, it appears that the mealybug system may provide
      evidence for stable maintenance of chromatin code not only through mitosis but
      also through meiosis.

PMID- 16575163
TI  - Genomic imprinting in plants and mammals: how life history constrains
      convergence.
AB  - In both flowering plants and mammals, DNA methylation is involved in silencing
      alleles of imprinted genes, but surprising differences in imprinting control are
      emerging between the two taxa which may be traced to differences in their life
      cycles. Imprinted gene expression in plants occurs in the endosperm, a separate
      fertilisation product which transmits nutrients to the embryo and does not
      contribute a genome to the next generation. Regulation of expression of the known
      imprinted genes in Arabidopsis involves a cascade of gene expression beginning in
      the gametophyte, a haploid life phase interposed between the meiotic products and
      the gametes, which evolved from free-living organisms that constitute the
      dominant life phase of lower plants. Although the gametophytes of flowering
      plants are highly reduced they still express large numbers of genes, perhaps
      reflecting their evolutionary legacy, and which may now be recruited for control
      of imprinting. Strikingly, the genes at the top of the expression cascade appear
      to be specifically activated by demethylation, rather than targeted for
      silencing. Unlike in mammals, there is no evidence for global resetting of
      methylation in plants, and although imprinting involves the activity of a
      maintenance methyltransferase, de novo methyltransferases do not appear to be
      required. Plants do not set aside a germline; instead the cells that undergo
      meiosis to produce gametophytes differentiate in the adult plant during flower
      development. Both the late differentiation of the lineage producing germ cells,
      and the extent of gene expression during the haploid phase, may be incompatible
      with global resetting of methylation. Resetting may be unnecessary in any case
      because the adult plant expresses imprinted loci either biallelically or not at
      all, suggesting there is no chromosomal memory of parent-of-origin in the lineage
      that produces the gametophytes. Thus several features of the plant life cycle may
      account for the different strategies used by plants and animals to regulate
      parent-specific gene expression.

PMID- 16575164
TI  - Intragenomic politics.
AB  - The mammalian genome contains multiple genetic factions with distinct interests
      in the outcomes of interactions among kin. In the context of an offspring's
      relations with its mother, these factions are proposed to align into two
      'parties', one favoring increased demand by offspring and the other favoring
      reduced demand. A possible alignment has inhibitors of demand located on the X
      chromosome and enhancers of demand located on autosomes, because X-linked loci
      are maternally derived two-thirds of the time by contrast to autosomal loci which
      are maternally derived half of the time.

PMID- 16575165
TI  - Evolution of the vertebrate DNMT3 gene family: a possible link between existence
      of DNMT3L and genomic imprinting.
AB  - DNA methylation plays an essential role in genomic imprinting observed in
      eutherian mammals and marsupials. In mouse, one of the two de novo DNA
      methyltransferases, Dnmt3a, and a related protein, Dnmt3L have been shown to be
      essential for imprint establishment in the parental germline. To gain insights
      into the evolution of imprinting mechanisms, we have identified and characterized
      the DNMT3 family genes in other vertebrate species. We cloned cDNAs for chicken
      DNMT3A and DNMT3B, whose putative protein products shared 81.5% and 48.6% amino
      acid sequence identity with their mouse orthologues. Using computer-assisted
      database searches, we also identified DNMT3A and DNMT3B orthologues in fish (fugu
      and zebrafish) and marsupials (opossum). We found that, while opossums had an
      orthologue for DNMT3L, chickens and fish did not have this gene. Thus, unlike the
      other DNMT3 members, DNMT3L was restricted to the species in which imprinting
      occurs. The acquisition of DNMT3L by a common ancestor of eutherians and
      marsupials might have been closely related to the evolution of imprinting.

PMID- 16575166
TI  - How imprinting centres work.
AB  - Imprinted genes tend to be clustered in the genome. Most of these clusters have
      been found to be under the control of discrete DNA elements called imprinting
      centres (ICs) which are normally differentially methylated in the germline. ICs
      can regulate imprinted expression and epigenetic marks at many genes in the
      region, even those which lie several megabases away. Some of the molecular and
      cellular mechanisms by which ICs control other genes and regulatory regions in
      the cluster are becoming clear. One involves the insulation of genes on one side
      of the IC from enhancers on the other, mediated by the insulator protein CTCF and
      higher-order chromatin interactions. Another mechanism may involve non-coding
      RNAs that originate from the IC, targeting histone modifications to the
      surrounding genes. Given that several imprinting clusters contain CTCF dependent
      insulators and/or non-coding RNAs, it is likely that one or both of these two
      mechanisms regulate imprinting at many loci. Both mechanisms involve a variety of
      epigenetic marks including DNA methylation and histone modifications but the
      hierarchy of and interactions between these modifications are not yet understood.
      The challenge now is to establish a chain of developmental events beginning with
      differential methylation of an IC in the germline and ending with imprinting of
      many genes, often in a lineage dependent manner.

PMID- 16575167
TI  - Genomic imprinting in the placenta.
AB  - Genomic imprinting is an epigenetic mechanism that is important for the
      development and function of the extra-embryonic tissues in the mouse. Remarkably
      all the autosomal genes which were found to be imprinted in the trophoblast
      (placenta) only are active on the maternal and repressed on the paternal allele.
      It was shown for several of these genes that their paternal silencing is not
      dependent on DNA methylation, at least not in its somatic maintenance. Rather,
      recent studies in the mouse suggest that placenta-specific imprinting involves
      repressive histone modifications and non-coding RNAs. This mechanism of autosomal
      imprinting is similar to imprinted X chromosome inactivation in the placenta.
      Although the underlying reasons remain to be explored, this suggests that
      imprinting in the placenta and imprinted X inactivation are evolutionarily
      related.

PMID- 16575168
TI  - Small non-coding RNAs and genomic imprinting.
AB  - Experimental and computer-assisted approaches have led to the identification of
      hundreds of imprinted small RNA genes, mainly clustered in two chromosomal
      domains (human 15q11-->q13 and 14q32 loci). The genes are only detected in
      placental mammals and belong to the C/D RNA and microRNA gene families. These are
      small non-coding RNAs involved in RNA-guided post-transcriptional RNA
      modifications and RNA-mediated gene silencing, respectively. Here, we discuss
      their potential functions and report the identification of novel small RNA genes
      lying within (or nearby) known imprinted chromosomal domains.

PMID- 16575169
TI  - Repetitive elements in imprinted genes.
AB  - Genomic imprinting in mammals results in mono-allelic expression of about 80
      genes depending on the parental origin of the alleles. Though the epigenetic
      mechanisms underlying imprinting are rather clear, little is known about the
      genetic basis for these epigenetic mechanisms. It is still rather enigmatic which
      sequence features discriminate imprinted from non-imprinted genes/regions and why
      and how certain sequence elements are recognized and differentially marked in the
      germlines. It seems likely that specific DNA elements serve as signatures that
      guide the necessary epigenetic modification machineries to the imprinted regions.
      Inter- and intraspecific comparative genomic studies suggest that the unusual
      occurrence and distribution of various types of repetitive elements within
      imprinted regions may represent such genomic imprinting signatures. In this
      review we summarize the various observations made and discuss them in light of
      experimental data.

PMID- 16575170
TI  - The role of DMDs in the maintenance of epigenetic states.
AB  - An important aspect of genome reprogramming is the establishment and maintenance
      of gamete-specific DNA methylation patterns that distinguish the parental alleles
      of imprinted genes. Disrupting the accurate transmission of genomic imprints by
      interfering with these methylation patterns causes severe defects in fetal growth
      and development. The inheritance of sex-specific DNA methylation patterns from
      both parents is thus a fundamental molecular definition of genomic imprinting.
      The other cardinal aspect is the regulation of imprinted gene expression over a
      long genomic distance, spanning a few clustered imprinted genes. There is
      converging experimental evidence that differentially methylated domains (DMDs),
      located in non-coding regions of imprinted genes, are involved in both processes.
      As such, DMDs are the imprinting backbone upon which the fundamental processes of
      sex-specific methylation and imprinted gene expression are built.

PMID- 16575171
TI  - Regulation of imprinted DNA methylation.
AB  - DNA methylation is an essential enzymatic modification in mammals. This common
      epigenetic mark occurs predominantly at the fifth carbon of cytosines within the
      palindromic dinucleotide 5'-CpG-3'. The majority of methylated CpGs are located
      within repetitive elements including centromeric repeats, satellite sequences and
      gene repeats encoding ribosomal RNAs. CpG islands, frequently located at the 5'
      end of genes, are typically unmethylated. DNA methylation also occurs at
      imprinted genes which exhibit parent-of-origin-specific patterns of methylation
      and expression. Imprinted methylation at differentially methylated domains (DMDs)
      is one of the regulatory mechanisms controlling the allele-specific expression of
      imprinted genes. Proper control of DNA methylation is needed for normal
      development and loss of methylation control can contribute to initiation and
      progression of tumorigenesis (reviewed in Plass and Soloway, 2002). Because
      patterns of imprinted DNA methylation are highly reproducible, imprinted loci
      make useful models for studying regulation of DNA methylation and may provide
      insights into how this regulation goes awry in cancer. Here, we review what is
      currently known about the mechanisms regulating imprinted DNA methylation. We
      will focus on cis-acting DNA sequences, trans-acting protein factors and the
      possible involvement of RNAs in control of imprinted DNA methylation.

PMID- 16575172
TI  - Bisulfite sequencing and dinucleotide content analysis of 15 imprinted mouse
      differentially methylated regions (DMRs): paternally methylated DMRs contain less
      CpGs than maternally methylated DMRs.
AB  - Imprinted genes in mammals show monoallelic expression dependent on parental
      origin and are often associated with differentially methylated regions (DMRs).
      There are two classes of DMR: primary DMRs acquire gamete-specific methylation in
      either spermatogenesis or oogenesis and maintain the allelic methylation
      differences throughout development; secondary DMRs establish differential
      methylation patterns after fertilization. Targeted disruption of some primary
      DMRs showed that they dictate the allelic expression of nearby imprinted genes
      and the establishment of the allelic methylation of secondary DMRs. However, how
      primary DMRs are recognized by the imprinting machinery is unknown. As a step
      toward elucidating the sequence features of the primary DMRs, we have determined
      the extents and boundaries of 15 primary mouse DMRs (including 12 maternally
      methylated and three paternally methylated DMRs) in 12.5-dpc embryos by bisulfite
      sequencing. We found that the average size of the DMRs was 3.2 kb and that their
      average G+C content was 54%. Dinucleotide content analysis of the DMR sequences
      revealed that, although they are generally CpG rich, the paternally methylated
      DMRs contain less CpGs than the maternally methylated DMRs. Our findings provide
      a basis for the further characterization of DMRs.

PMID- 16575173
TI  - Genomic imprinting in Dicer1-hypomorphic mice.
AB  - To address the function of RNA interference (RNAi) in transcriptional silencing
      in mammals, we analyzed genomic imprinting in Dicer1-hypomorphic mice, in which
      Dicer1 expression was significantly reduced. We did not observe any abnormality
      in the allelic expression of imprinted genes in these mice or their offspring,
      suggesting that reduced expression of Dicer1 did not significantly affect the
      maintenance and reprogramming of imprinting.

PMID- 16575174
TI  - Genome-wide survey of imprinted genes.
AB  - The developmental failure of mammalian parthenogenote has been a mystery for a
      long time and posed a question as to why bi-parental reproduction is necessary
      for development to term. In the 1980s, it was proven that this failure was not
      due to the genetic information itself, but to epigenetic modification of genomic
      DNA. In the following decade, several studies successfully identified imprinted
      genes which were differentially expressed in a parent-of-origin-specific manner,
      and it was shown that the differential expression depended on the pattern of DNA
      methylation. These facts prompted development of genome-wide systematic screening
      methods based on DNA methylation and differential gene expression to identify
      imprinted genes. Recently computational approaches and microarray technology have
      been introduced to identify imprinted genes/loci, contributing to the expansion
      of our knowledge. However, it has been shown that the gene silencing derived from
      genomic imprinting is accomplished by several mechanisms in addition to direct
      DNA methylation, indicating that novel approaches are further required for
      comprehensive understanding of genomic imprinting. To unveil the mechanism of
      developmental failure in mammalian parthenogenote, systematic screenings for
      imprinted genes/loci have been developed. In this review, we describe genomic
      imprinting focusing on the history of genome-wide screening.

PMID- 16575175
TI  - Establishment and maintenance of H19 imprinting in the germline and
      preimplantation embryo.
AB  - The mouse H19 and Igf2 genes are oppositely imprinted and share enhancers that
      reside 3' to the genes. The imprinted expression of these genes is coordinated by
      a 2-kb regulatory element, the differentially methylated domain (DMD), positioned
      between the two genes. The methylation status of this region determines the
      ability of the insulator factor CTCF to bind to its sites in the DMD. Deletions
      and mutations of the DMD that affect imprinting in the soma have little effect on
      the methylation pattern of H19 in the germline, suggesting that additional
      sequences and factors contribute to the earliest stages of imprinting regulation
      at this locus. Less is known about these initial steps, which include the marking
      of the parental alleles, the onset of allele-specific expression patterns and
      maintenance of the imprints in the preimplantation embryo. Here, we will focus on
      these early steps, summarizing what is known and what questions remain to be
      addressed.

PMID- 16575176
TI  - Lessons from comparative analysis of species-specific imprinted genes.
AB  - Genomic imprinting is generally believed to be conserved in all mammals except
      for egg-laying monotremes, suggesting that it is closely related to placental and
      fetal growth. As expected, the imprinting status of most imprinted genes is
      conserved between mouse and human, and some are imprinted even in marsupials. On
      the other hand, a small number of genes were reported to exhibit species-specific
      imprinting that is not necessarily accounted for by either the placenta or
      conflict hypotheses. Since mouse and human represent a single, phylogenetically
      restricted clade in the mammalian class, a much broader comparison including
      mammals diverged earlier than rodents is necessary to fully understand the
      species-specificity and variation in evolution of genomic imprinting. Indeed,
      comparative analysis of a species-specific imprinted gene Impact using a broader
      range of mammals led us to propose an alternative dosage control hypothesis for
      the evolution of genomic imprinting.

PMID- 16575177
TI  - The imprinted mouse Igf2r/Air cluster--a model maternal imprinting system.
AB  - Every diploid organism inherits a complete chromosome set from its father and
      mother in addition to the sex chromosomes, so that all autosomal genes are
      available in two copies. For most genes, both copies are expressed without
      preference. Imprinted genes, however, are expressed depending on their parental
      origin, being active on the paternal or maternal allele only. To date 73
      imprinted genes are known in mouse (www.mgu.har.mrc.ac.uk/research/imprinting),
      37 show paternal expression while 36 show maternal expression, indicating no bias
      for imprinting to occur in one sex or the other. Therefore, two different
      parental-specific imprinting systems may have evolved in mammals, acting
      specifically in the paternal or maternal gamete. Similarities and differences
      between the two imprinting systems will be reviewed, with specific reference to
      the role of non-coding RNAs and chromatin modifications. The mouse Igf2r/Air
      cluster is presented as a model of the maternal imprinting system.

PMID- 16575178
TI  - Imprinting the Gnas locus.
AB  - Gnas is an enigmatic and rather complex imprinted gene locus. A single
      transcription unit encodes three, and possibly more, distinct proteins. These are
      determined by overlapping transcripts from alternative promoters with different
      patterns of imprinting. The canonical Gnas transcript codes for Gsalpha, a highly
      conserved signalling protein and an essential intermediate in growth,
      differentiation and homeostatic pathways. Monoallelic expression of Gnas is
      highly tissue-restricted. The alternative transcripts encode XLalphas, an unusual
      variant of Gsalpha, and the chromogranin-like protein Nesp55. These transcripts
      are expressed specifically from the paternal and maternal chromosomes,
      respectively. Their existence in the Gnas locus might imply functional
      connections amongst them or with Gsalpha. In this review, we consider how
      imprinting of Gnas was discovered, the phenotypic consequences of mutations in
      each of the gene products, both in the mouse and human, and provide some
      conjectures to explain why this elaborate imprinted locus has evolved in this
      manner in mammals.

PMID- 16575179
TI  - The H19 gene: regulation and function of a non-coding RNA.
AB  - The H19 gene encodes a 2.3-kb non-coding mRNA which is strongly expressed during
      embryogenesis. This gene belongs to an imprinted cluster, conserved on mouse
      chromosome 7 and human chromosome 11p15. H19 is maternally expressed and the
      neighbouring Igf2 gene is transcribed from the paternal allele. These two genes
      are co-expressed in endoderm- and mesoderm-derived tissues during embryonic
      development, which suggests a common mechanism of regulation. The regulatory
      elements (imprinted control region, CTCF insulation, different enhancer
      sequences, promoters of the two genes, matrix attachment regions) confer a
      differential chromatin architecture to the two parental alleles leading to
      reciprocal expression. The role of the H19 gene is unclear but different aspects
      have been proposed. H19 influences growth by way of a cis control on Igf2
      expression. Although H19(-/-) mice are viable, a role for this gene during
      development has been suggested by viable H19(-/-) parthenogenetic mice. Finally
      it has been described as a putative tumour suppressor gene. H19 has been studied
      by numerous laboratories over the last fifteen years, nevertheless the function
      of this non-coding RNA remains to be elucidated.

PMID- 16575180
TI  - Imprinting control within the compact Gnas locus.
AB  - Mouse distal chromosome 2 was one of the earliest described imprinting regions.
      Maternal and paternal inheritance of the region is associated with opposite
      phenotypes affecting growth, development and behaviour. Mis-expression of
      proteins determined by the imprinted Gnas locus can account for the phenotypes.
      The imprinting domain in mouse distal chromosome 2 is small, comprising the Gnas
      locus. This locus is unusually complex, containing biallelic, maternally and
      paternally expressed transcripts that share exons. It also contains two germline
      differentially methylated regions that have the characteristics of imprinting
      control regions. One of these specifically controls the tissue-specific
      imprinting of the Gnas exon 1 transcript but does not affect the imprinting of
      other transcripts. Imprinting of other transcripts may be controlled by the other
      germline differentially methylated region by a mechanism involving antisense RNA.

PMID- 16575181
TI  - Cross-species clues of an epigenetic imprinting regulatory code for the IGF2R
      gene.
AB  - The epigenetic marks on the IGF2R gene that encodes a receptor responsible for
      IGF-II degradation consist of differentially methylated DNA in association with
      multiple modifications on the associated histones. We review these epigenetic
      marks across various species during the evolution of IGF2R imprinting. Both IGF2
      and IGF2R genesare imprinted in the mammal lineage that diverged from Monotremata
      approximately 150 million years ago. While IGF2 is consistently imprinted in all
      mammals following its divergence, IGF2R imprinting disappears in the Euarchonta
      lineage, including human species, approximately 75 million years ago.
      Differential DNA methylation marks on the two parental alleles correlate with
      imprinting in all imprinted genes including IGF2R. While the DNA methylation
      marks in the IGF2R promoter region 1 (DMR1) correlate with IGF2R allelic
      expression, the DNA methylation marks in the intron region 2 (DMR2) fail to
      correlate with IGF2R imprinting status in a number of species. Human IGF2R and
      mouse neuronal Igf2r are not imprinted despite the presence of DMR2. We have
      noted that human IGF2R is not imprinted in more than 100 informative samples
      including various tumor tissues. Furthermore, opossum (Marsupialia) IGF2R is
      consistently imprinted despite the absence of DMR2. These lines of evidence
      indicate that DNA methylation marks in DMR2 are neither necessary nor sufficient
      for consistent imprinting of IGF2R across species. Histone modification marks,
      however, correlate more consistently with the tissue-specific and species
      specific imprinting status of IGF2R in human and mouse. Acetylated histone H3 and
      H4 and methylated lysine 4 of H3 (H3-K4Me) associate with transcriptionally
      active alleles while tri-methylated lysine 9 of H3 (H3-K9Me3) marks the silenced
      alleles. In the mouse, an antisense non-coding transcript called Air is
      transcribed from DMR2 on the paternal allele, and this imprinted transcript plays
      a central role in Igf2r imprinting. Mouse Igf2r imprinting depends on an Air RNA
      while the existence of AIR in other species is unknown. Overall, DNA methylation,
      histone acetylation, and histone methylation play a vital role in coordinating
      IGF2R allelic expression across all species. Rare monoallelic or skewed allelic
      expression of human IGF2R and their biological importance warrants further
      rigorous study.

PMID- 16575182
TI  - Imprinting in neurons.
AB  - Although most imprinted genes display parent-origin-specific gene expression in
      tissues where they are transcribed, some genes are imprinted in a tissue-specific
      manner. Genes that show brain-specific imprinting or brain-specific lack of
      imprinting present a unique opportunity to study the process of imprinting during
      tissue differentiation. In this review, I introduce the systematic study of brain
      cell-lineage-specific imprinting using a primary brain cell culture system, where
      neurons or glial cells are cultured separately. Two reports using the primary
      brain cell culture revealed brain-cell-lineage-specific imprinting in Ube3a and
      Igf2r, which had previously been described to show brain-specific imprinting and
      brain-specific lack of imprinting, respectively. Such brain-cell-lineage-specific
      imprinting was associated with cell-specific epigenetic modifications, especially
      with their reciprocally imprinted antisense non-coding RNAs, Ube3a-ATS and Air.
      These results emphasize the necessity of imprinting analysis at the cell level
      rather than in whole brain tissue during brain differentiation. The brain cell
      culture system provides us with a new powerful tool to understand the molecular
      mechanism of brain-specific imprinting.

PMID- 16575183
TI  - Analysis of mouse conceptuses with uniparental duplication/deficiency for distal
      chromosome 12: comparison with chromosome 12 uniparental disomy and implications
      for genomic imprinting.
AB  - Distal mouse chromosome 12 is imprinted. Phenotypic analysis of mouse embryos
      with maternal or paternal uniparental disomy for the whole of chromosome 12 has
      characterized the developmental defects associated with the altered dosage of
      imprinted genes on this chromosome. Here we conduct a characterization of
      maternal and paternal Dp(dist12) mice using the reciprocal translocation
      T(4;12)47H. This limits the region analysed to the chromosomal domain distal to
      the T47H breakpoint in B3 on mouse chromosome 12. Both MatDp(dist12)T47H and
      PatDp(dist12)T47H conceptuses are non-viable and the frequency of recovery of
      Dp(dist12) conceptuses by 10.5 days post coitum (dpc) was lower than expected
      after normal adjacent-1 disjunction. A subset of MatDp(dist12) embryos can
      survive up to one day post partum. In contrast to paternal uniparental disomy 12
      embryos, no live PatDp (dist12) embryos were recovered after 16.5 days of
      gestation. Other phenotypes observed in maternal and paternal chromosome 12
      uniparental disomy mice are recapitulated in the Dp(dist12) mice and include
      placental, muscle and skeletal defects. Additional defects were also noted in the
      skin of both MatDp(dist12) and maternal uniparental disomy 12 embryos. This study
      shows that the developmental abnormalities associated with the altered parent of
      origin for mouse chromosome 12 can be attributed to the genomic region distal to
      the T47H breakpoint.

PMID- 16575184
TI  - Aberrant regulation of imprinted gene expression in Gtl2lacZ mice.
AB  - The imprinted region on mouse distal chromosome 12 covers about 1 Mb and contains
      at least three paternally expressed genes (Pegs: Peg9/Dlk1, Peg11/Rtl1, and Dio3)
      and four maternally expressed genes (Megs: Meg3/Gtl2, antiPeg11/antiRlt1,
      Meg8/Rian, and Meg9/Mirg). Gtl2(lacZ) (Gene trap locus 2) mice have a transgene
      (TG) insertion 2.3 kb upstream from the Meg3/Gtl2 promoter and show about 40%
      growth retardation when the TG-inserted allele is paternally derived.
      Quantitative RT-PCR experiments showed that the expression levels of Pegs in this
      region were reduced below 50%. These results are consistent with the observed
      phenotype in Gtl2lacZ mice, because at least two Pegs(Peg9/Dlk1 and Dio3) have
      growth-promoting effects. The aberrant induction of Megs from silent paternal
      alleles was also observed in association with changes in the DNA methylation
      level of a differentially methylated region (DMR) located around Meg3/Gtl2 exon
      1. Interestingly, a 60 approximately 80% reduction in all Megs was observed when
      the TG was maternally derived, although the pups showed no apparent growth or
      morphological abnormalities. Therefore, the paternal or maternal inheritance of
      the TG results in the down-regulation in cis of either Pegs or Megs,
      respectively, suggesting that the TG insertion influences the mechanism
      regulating the entire imprinted region.

PMID- 16575185
TI  - The 3' portion of the mouse H19 Imprinting-Control Region is required for proper
      tissue-specific expression of the Igf2 gene.
AB  - Genomic imprinting at the H19/Igf2 locus is governed by a cis-acting Imprinting
      Control Region (ICR), located 2 kb upstream of the H19 gene. This region
      possesses an insulator function which is activated on the unmethylated maternal
      allele through the binding of the CTCF factor. It has been previously reported
      that paternal transmission of the H19(SilK) deletion, which removes the 3'
      portion of H19 ICR, leads to the loss of H19 imprinting. Here we show that, in
      the liver, this reactivation of the paternal H19 gene is concomitant to a
      dramatic decrease in Igf2 mRNA levels. This deletion alters higher-order
      chromatin architecture, Igf2 promoter usage and tissue-specific expression.
      Therefore, when methylated, the 3' portion of the H19 ICR is a bi-functional
      regulatory element involved not only in H19 imprinting but also in 'formatting'
      the higher-order chromatin structure for proper tissue-specific expression of
      both H19 and Igf2 genes.

PMID- 16575186
TI  - Mutagenesis in mice of nuclear hormone receptor binding sites in the Igf2/H19
      imprinting control region.
AB  - The H19/Igf2 imprinting control region (ICR) is a DNA methylation-dependent
      chromatin insulator in somatic cells. The hypomethylated maternally inherited ICR
      binds the insulator protein CTCF at four sites, and blocks activity of the
      proximal Igf2 promoter by insulating it from the shared distal enhancers. The
      hypermethylated paternally inherited ICR lacks CTCF binding and insulator
      activity, but induces methylation-silencing of the paternal H19 promoter. The
      paternal-specific methylation of the ICR is established in the male germ cells,
      while the ICR emerges from the female germ line in an unmethylated form. Despite
      several attempts to find cis-regulatory elements, it is still unknown what
      determines these male and female germ cell-specific epigenetic modifications. We
      recently proposed that five in vivo footprints spanning fifteen half nuclear
      hormone receptor (NHR) binding sites within the ICR might be involved, and here
      we report on the effects of mutagenizing all of these half sites in mice. No
      effect was obtained--in the female and male germ lines the mutant ICR remained
      hypomethylated and hypermethylated, respectively. The ICR imprinting mechanism
      remains undefined.

PMID- 16575187
TI  - Establishment of the primary imprint of the HYMAI/PLAGL1 imprint control region
      during oogenesis.
AB  - Imprinting within domains occurs through epigenetic alterations to imprinting
      centers (ICs) that result in the establishment of parental-specific differences
      in gene expression. One candidate IC lies within the imprinted domain on human
      chromosome region 6q24. This domain contains two paternally expressed genes, the
      zinc finger protein gene PLAGL1 (ZAC/LOT1) and an untranslated mRNAcalled HYMAI.
      The putative IC overlaps exon 1 of HYMAI and is differentially methylated in
      somatic tissues. In humans, loss of methylation within this region is seen in
      some patients with transient neonatal diabetes mellitus, and hypermethylation of
      this region is found in ovarian cancer and is associated with changes in
      expression of PLAGL1, suggesting that it plays a key role in regulating gene
      expression. Differential methylation within this region is conserved in the
      homologous region on mouse chromosome 10A and is present on the maternal allele.
      In this paper, we report that DNA methylation is established during the growth
      phase of oogenesis and that this coincides with the establishment of monoallelic
      expression from this region lending further support to the hypothesis that this
      region functions as an IC.

PMID- 16575188
TI  - An oligonucleotide microarray for mouse imprinted genes profiling.
AB  - Genomic imprinting is an epigenetic phenomenon unique to mammals that causes some
      genes to be expressed according to their parental origin. It results in
      developmental asymmetry in the function of the parental genomes. We describe here
      a method for the profiling of imprinted genes based on the development of a mouse
      imprinting microchip containing oligonucleotides corresponding to 493 genes,
      including most of the known imprinted genes (IG = 63), genes involved in
      epigenetic processes (EPI = 15), in metabolism (= 147), in obesity (= 10) and in
      neurotransmission (= 256) and housekeeping reference genes (= 2). This custom
      oligonucleotide microarray has been constructed to make data analysis and
      handling more manageable than pangenomic microarrays. As a proof of concept we
      present the differential expression of these 493 genes in different tissues
      (liver, placenta, embryo) of C57BL6/J mice fed different diets. Appropriate
      experimental strategies and statistical tools were defined at each step of the
      data analysis process with regard to the different sources of constraints. Data
      were confirmed by expression analyses based on quantitative real-time PCR. These
      oligochips should make it possible to increase our understanding of the
      involvement of imprinted genes in the timing of expression programs, tissue by
      tissue, stage by stage, in response to nutrients, lifestyles and other as yet
      unknown critical environmental factors in a variety of physiopathological
      situations, and in animals of different strains, ages and sexes. The use of
      oligonucleotides makes it possible to expand this microchip to include the
      increasing number of imprinted genes discovered.

PMID- 16575189
TI  - Imprinted genes and their role in human fetal growth.
AB  - Growth is defined as the progressive increase in size and is listed as one of the
      eight main characteristics of life. In human gestation the most rapid growth
      phase is from 16 to 32 weeks when first there is both cell number and size
      increase and then from 32 weeks onwards there is continued size increase (Pollack
      and Divon, 1992). The mechanism of growth in utero is of fundamental interest to
      clinicians and scientists because of its implications for neonatal health. Growth
      is multifactorial in origin with both genetics and environment contributing
      equally large parts. Despite this complexity analysis of the candidate genes
      involved is possible using simple tissue biopsies at the relevant stages of
      development. Of particular interest in understanding fetal growth is the analysis
      of a group of genes that show a parent-of-origin effect known as genomic
      imprinting. Imprinted genes are not only found in eutherian (placental) and
      metatherian (marsupial) mammals but surprisingly also in plants. Nevertheless,
      their evolution in mammals appears to be linked primarily to placentation. It is
      thought to result from a potential conflict between the parents in terms of the
      drive to successfully propagate their own separate genes and the mother's added
      drive for her survival through the pregnancy to reproduce again. This means that
      the mother wants to restrict fetal growth and the father to enhance it.

PMID- 16575190
TI  - Imprinted genes in placental growth and obstetric disorders.
AB  - Genomic imprinting has a special role in placental biology. Imprinted genes are
      often strongly expressed in the placenta, and the allelic expression bias due to
      imprinting is sometimes stronger in this extraembryonic organ than in the embryo
      and adult. Mutations, epimutations, and uniparental disomies affecting imprinted
      loci cause placental stunting or overgrowth in mice and humans, and placental
      neoplasms (complete hydatidiform moles) are androgenetic. Whether imprinted genes
      might also play a role in the more common medical conditions that affect the
      placenta, including preeclampsia and intrauterine growth restriction (IUGR), is
      an important question that is now receiving some attention. Here we review this
      area and describe recent data indicating altered expression of imprinted genes in
      the placental response to maternal vascular underperfusion associated with IUGR.

PMID- 16575191
TI  - Regulation of growth and metabolism by imprinted genes.
AB  - A small sub-set of mammalian genes are subject to regulation by genomic
      imprinting such that only one parental allele is active in at least some sites of
      expression. Imprinted genes have diverse functions, notably including the
      regulation of growth. Much attention has been devoted to the insulin-like growth
      factor signalling pathway that has a major influence on fetal size and contains
      two components encoded by the oppositely imprinted genes, Igf2 (a growth
      promoting factor expressed from the paternal allele) and Igf2r (a growth
      inhibitory factor expressed from the maternal allele). These genes fit the parent
      offspring conflict hypothesis for the evolution of genomic imprinting.
      Accumulated evidence indicates that at least one other fetal growth pathway
      exists that has also fallen under the influence of imprinting. It is clear that
      not all components of growth regulatory pathways are encoded by imprinted genes
      and instead it may be that within a pathway the influence of a single gene by
      each of the parental genomes may be sufficient for parent-offspring conflict to
      be enacted. A number of imprinted genes have been found to influence energy
      homeostasis and some, including Igf2 and Grb10, may coordinate growth with
      glucose-regulated metabolism. Since perturbation of fetal growth can be
      correlated with metabolic disorders in adulthood these imprinted genes are
      considered as candidates for involvement in this phenomenon of fetal programming.

PMID- 16575192
TI  - Imprinting defects on human chromosome 15.
AB  - The Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct
      neurogenetic diseases that are caused by the loss of function of imprinted genes
      on the proximal long arm of human chromosome 15. In a few percent of patients
      with PWS and AS, the disease is due to aberrant imprinting and gene silencing. In
      patients with PWS and an imprinting defect, the paternal chromosome carries a
      maternal imprint. In patients with AS and an imprinting defect, the maternal
      chromosome carries a paternal imprint. Imprinting defects offer a unique
      opportunity to identify some of the factors and mechanisms involved in imprint
      erasure, resetting and maintenance. In approximately 10% of cases the imprinting
      defects are caused by a microdeletion affecting the 5' end of the SNURF-SNRPN
      locus. These deletions define the 15q imprinting center (IC), which regulates
      imprinting in the whole domain. These findings have been confirmed and extended
      in knock-out and transgenic mice. In the majority of patients with an imprinting
      defect, the incorrect imprint has arisen without a DNA sequence change, possibly
      as the result of stochastic errors of the imprinting process or the effect of
      exogenous factors.

PMID- 16575193
TI  - The Prader-Willi/Angelman imprinted domain and its control center.
AB  - The present review focuses on the recent advances towards understanding the mode
      of operation of the imprinting center (IC) within the Prader-Willi/Angelman
      syndromes (PWS/AS) domain. Special emphasis is put on the elucidation of the
      functional interaction between the two parts of the center, AS-IC and PWS-IC. The
      recent studies, on which the review is based, reveal cis-acting elements and
      trans-acting proteins that constitute the two parts of the IC and presumably
      provide the molecular mechanism for this interaction. AS-IC acquires the primary
      imprint during gametogenesis by establishing the maternal epigenotype. The
      unmethylated maternal allele of the AS-IC binds, very likely, a trans-acting
      factor that confers methylation on the PWS-IC maternal allele after
      fertilization. It is assumed that the PWS-IC paternal epigenotype, once
      established, spreads across the entire PWS/AS domain in the soma.

PMID- 16575194
TI  - Imprinting disruption of the CDKN1C/KCNQ1OT1 domain: the molecular mechanisms
      causing Beckwith-Wiedemann syndrome and cancer.
AB  - Human chromosomal region 11p15.5, which is homologous to mouse chromosome region
      7F5, is a well-known imprinted region. The CDKN1C/KCNQ1OT1 imprinted domain,
      which is one of two imprinted domains at 11p15.5, includes nine imprinted genes
      regulated by an imprinting center (IC). The CDKN1C/KCNQ1OT1 IC is a
      differentially methylated region of KCNQ1OT1(KCNQ1OT-DMR) with DNA methylation on
      the maternal allele and no methylation on the paternal allele. CDKN1C (alias
      p57KIP2), an imprinted gene with maternal expression, encoding a cyclin-dependent
      kinase inhibitor, is a critical gene within the CDKN1C/KCNQ1OT1 domain. In
      Beckwith-Wiedemann syndrome (BWS), approximately 50% of patients show loss of DNA
      methylation accompanied by loss of histone H3 Lys9 dimethylation on maternal
      KCNQ1OT-DMR, namely an imprinting disruption, leading to diminished expression of
      CDKN1C. In cancer, at least three molecular mechanisms--imprinting disruption,
      aberrant DNA methylations at the CDKN1C promoter, and loss of heterozygosity
      (LOH) of the maternal allele--are seen and all three result in diminished
      expression of CDKN1C. Imprinting disruption of the CDKN1C/KCNQ1OT1 domain is
      involved in the development of both BWS and cancer and it changes the maternal
      epigenotype to the paternal type, leading to diminished CDKN1C expression. In
      this review, we describe recent advances in epigenetic control of the
      CDKN1C/KCNQ1OT1 imprinted domain in both humans and mice.

PMID- 16575195
TI  - New chromosome 11p15 epigenotypes identified in male monozygotic twins with
      Beckwith-Wiedemann syndrome.
AB  - Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome demonstrating
      heterogeneous molecular alterations of two imprinted domains on chromosome 11p15.
      The most common molecular alterations include loss of methylation at the proximal
      imprinting center, IC2, paternal uniparental disomy (UPD) of chromosome 11p15 and
      hypermethylation at the distal imprinting center, IC1. An increased incidence of
      female monozygotic twins discordant for BWS has been reported. The molecular
      basis for eleven such female twin pairs has been demonstrated to be a loss of
      methylation at IC2, whereas only one male monozygotic twin pair has been reported
      with this molecular defect. We report here two new pairs of male monozygotic
      twins. One pair is discordant for BWS; the affected twin exhibits paternal UPD
      for chromosome 11p15 whereas the unaffected twin does not. The second male twin
      pair is concordant for BWS and both twins of the pair demonstrate
      hypermethylation at IC1. Thus, this report expands the known molecular etiologies
      for BWS twins. Interestingly, these findings demonstrate a new epigenotype
      phenotype correlation in BWS twins. That is, while female monozygotic twins with
      BWS are likely to show loss of imprinting at IC2, male monozygotic twins with BWS
      reflect the molecular heterogeneity seen in BWS singletons. These data underscore
      the need for molecular testing in BWS twins, especially in view of the known
      differences among 11p15 epigenotypes with respect to tumor risk.

PMID- 16575196
TI  - The dynamics of imprinted X inactivation during preimplantation development in
      mice.
AB  - In the mouse, there are two forms of X chromosome inactivation (XCI), random XCI
      in the fetus and imprinted paternal XCI, which is limited to the extraembryonic
      tissues. While the mechanism of random XCI has been studied extensively using the
      in vitro XX ES cell differentiation system, imprinted XCI during early embryonic
      development has been less well characterized. Recent studies of early embryos
      have reported unexpected findings for the paternal X chromosome (Xp). Imprinted
      XCI may not be linked to meiotic silencing in the male germ line but rather to
      the imprinted status of the Xist gene. Furthermore, the Xp becomes inactivated in
      all cells of cleavage-stage embryos and then reactivated in the cells of the
      inner cell mass (ICM) that form the epiblast, where random XCI ensues.

PMID- 16575197
TI  - A SAGE approach to identifying novel trans-acting factors involved in the X
      inactivation process.
AB  - X chromosome inactivation ensures the dosage compensation of X-linked genes in XX
      females compared to their XY male counterpart. It is characterised by the
      specific recruitment of an inhibitory ribonucleoprotein complex involving the non
      coding Xist RNA to the presumptive inactive X chromosome and associated chromatin
      modifications, which result in the transcriptional silencing of the X chromosome.
      As an approach to the identification of some of the potential molecular players
      in this process we have performed comparative transcriptional profiling of mouse
      6.5-dpc (days post-coitum) female and male embryos using a modified SAGE (Serial
      analysis of gene expression) technique which allows the analysis of small
      quantities of biological material. At 6.5 dpc, a moment when random X
      inactivation of embryonic tissues has just been achieved, some two hundred
      transcripts that were significantly enriched in the female gastrula compared to
      its male counterpart could be identified. The validation of an association with
      the X inactivation process of a subset of these transcripts has been studied, ex
      vivo, in differentiating female and male ES cells and in female ES cells in which
      the establishment of X inactivation is interrupted through the post
      transcriptional inhibition of Xist synthesis.

PMID- 16575198
TI  - Evolution of mammalian X chromosome-linked imprinting.
AB  - We analyse the evolution of X chromosome-linked imprinting by modifying our
      previous model of imprinting of autosomal genes that influence the trade-off
      between maternal fecundity and offspring viability through alterations in
      maternal investment (Mills and Moore, 2004). Unlike previous genetic models, we
      analyse X-linked imprinting in the context of populations at equilibrium for
      either autosomal or X-linked biallelically expressed alleles at loci that
      influence the fecundity/viability trade-off. We show that selection under
      parental conflict over maternal investment in offspring can parsimoniously
      explain the occurrence of sex-specific gene expression patterns, without a
      requirement to postulate direct selection for sexual dimorphism mediated through
      imprinting. We note that sex chromosome imprinting causes a small distortion of
      the post-weaning sex ratio, providing a possible selection pressure against the
      evolution of X-linked imprints. We discuss our conclusions in the context of
      recent reports of imprinting of mouse X-linked Xlr genes.

PMID- 16575199
TI  - Tsix-deficient X chromosome does not undergo inactivation in the embryonic
      lineage in males: implications for Tsix-independent silencing of Xist.
AB  - Differential induction of the X-linked non-coding Xist gene is a key event in the
      process of X inactivation occurring in female mammalian embryos. Xist is
      negatively regulated in cis by its antisense gene Tsix through modification of
      the chromatin structure. The maternal Xist allele, which is normally silent in
      the extraembryonic lineages, is ectopically activated when Tsix is disrupted on
      the same chromosome, and subsequently the maternal X chromosome undergoes
      inactivation in the extraembryonic lineages even in males. However, it is still
      unknown whether the single Tsix-deficient X chromosome (XDeltaTsix) in males is
      also inactivated in the embryonic lineage. Here, we show that both male and
      female embryos carrying a maternally derived XDeltaTsix could survive if the
      extraembryonic tissues were complemented by wild-type tetraploid cells. In
      addition, Xist on the XDeltaTsix was properly silenced and methylated at CpG
      sites in adult male somatic cells. These results indicate that the embryonic
      lethality caused by the maternal XDeltaTsix is solely attributable to the defects
      in the extraembryonic lineages. XDeltaTsix does not seem to undergo inactivation
      in the embryonic lineage in males, suggesting the presence of a Tsix-independent
      silencing mechanism for Xist in the embryonic lineage.

PMID- 16575200
TI  - ETS-TMPRSS2 fusion gene products in prostate cancer.
AB  - Genes playing a role in carcinogenesis have often been identified through
      analysis of recurrent chromosomal rearrangements. Although such rearrangements
      are well known in leukemias, lymphomas, and sarcomas, they have not been well
      characterized in carcinomas. In the October 28, 2005 issue of Science, a study by
      Tomlins et al. uses bioinformatics techniques to identify candidate oncogenic
      chromosomal changes based on analysis of outlier gene expression. The authors
      determined that two ETS transcription factors, ERG and ETV1 were outliers in
      prostate cancer. The group reports recurrent fusions of the 5' untranslated
      region of the TMPRSS2 gene to ERG and ETV1 in the majority of prostate cancer
      samples containing the outlier expression. In cell lines containing the fusion
      gene, androgen appears to play a role in mediating ETS overexpression. This
      fusion gene product may play an important role in the development, diagnosis, and
      treatment of prostate cancer.

PMID- 16575201
TI  - TKI-31 inhibits angiogenesis by combined suppression signaling pathway of VEGFR2
      and PDGFRbeta.
AB  - Tyrosine kinases have been strongly implicated as therapeutic targets that
      influence the angiogenic process in growing tumors. In this study, we revealed
      that TKI-31 is a potent broad spectrum tyrosine kinase inhibitor, which inhibits
      vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth
      factor receptor beta (PDGFRbeta) and also inhibits kinases of other class, such
      as c-Kit and c-Src on molecular base, but showed no activity against vascular
      endothelial growth factor receptor 1 (VEGFR1) and epidermal growth factor
      receptor (EGFR). TKI-31 inhibits VEGF-induced phosphorylation of VEGFR2 in
      endothelial cells as well as PDGF(BB)-induced phosphorylation in fibroblast
      cells, and leading to the inhibition of down-stream signaling triggered by these
      receptors such as PI3K/Akt/mTOR, MAPK42/44(ERK) and paxillin. TKI-31 also
      inhibited VEGF-induced endothelial cells proliferation, migration and their
      differentiation into capillary-like tube formation. Its anti-angiogenic property
      was further confirmed by the inhibition of neovascularization on CAM, in vivo.
      These results collectively highlight the therapeutic potential of this compound
      for the treatment of solid tumors and other diseases where angiogenesis plays an
      important role.

PMID- 16575202
TI  - Altered expression of alpha-dystroglycan subunit in human gliomas.
AB  - Dystroglycan (DG) is an integral membrane receptor of extracellular matrix
      proteins, composed of two subunits alpha and beta derived from a common
      precursor. In brain DG is expressed in neurons, glia limitans, astrocytic endfeet
      around vessels and endothelial cells. We investigate whether DG may play a role
      in brain tumors. Western blot and immunofluorescence analysis showed that, while
      beta-DG subunit was present, the highly glycosylated alpha-DG subunit was
      strongly reduced in surgically derived human glioblastoma biopsies, in low
      passage patient-derived cultures and in glioma cell lines, U87MG and A172MG, but
      not in all glioma cell lines tested. Immunohistochemistry of tumor frozen
      sections revealed that the loss of alpha-DG was confined in the tumor area but
      not around blood vessels. Overexpression of DG decreased the growth rate of the
      glioma cell lines lacking the highly glycosylated alpha-DG subunit and the colony
      forming efficiency. Clonogenic assay in presence of temozolomide showed an
      additive effect between DG overexpression and drug treatment. Our data suggest
      that DG may be involved in the progression of primary brain tumors.

PMID- 16575204
TI  - Likelihood for false positives using bacterially-expressed recombinant proteins
      in anti-angiogenesis studies.

PMID- 16575203
TI  - Treatment of high-grade glioma patients with the humanized anti-epidermal growth
      factor receptor (EGFR) antibody h-R3: report from a phase I/II trial.
AB  - The poor prognosis of patients with high-grade glioma has led to the search for
      new therapeutic strategies. More than half of these tumors overexpress Epidermal
      Growth factor Receptor (EGFR). h-R3 is a humanized monoclonal antibody that
      recognize the EGFR external domain with high affinity, inhibiting tyrosine kinase
      activation. In order to evaluate safety, immunogenicity and preliminary efficacy
      of h-R3 in newly diagnosed high-grade glioma patients, we conducted a Phase I/II
      trial. Patients received six weekly infusions of h-R3 at the dose of 200 mg in
      combination with external beam radiotherapy. Twenty-nine patients (mean age, 45
      years and median KPS 80) were entered into the study. Tumor types were:
      glioblastoma (GB) (16 patients), anaplastic astrocytoma (AA) (12 patients) and
      anaplastic oligodendroglioma (AO) (1 patient). All patients underwent debulking
      surgery or biopsy before entering the trial. The antibody was very well
      tolerated. No evidences of grade 3/4 adverse events were detected. None of the
      patients developed acneiform rash or allergic reactions. One patient developed a
      positive anti-idiotypic response. Objective response-rate was 37.9% (17.2%
      complete response, 20.7% partial response) while stable disease occurred in 41.4%
      of the patients. With a median follow up time of 29 months, the median survival
      is 22.17 months for all subjects. Median survival time (MST) is 17.47 months for
      GB, whereas MST is not reached for AA patients.

PMID- 16575206
TI  - Elegance, silence and nonsense in the mutations literature for solid tumors.
AB  - A third of highly cited clinical studies are subsequently contradicted, and there
      are statistical reasons for why many published research findings may be false.
      The subjective impression of many experts in cancer genetics is that much of the
      tumor mutation literature may also be erroneous or deeply flawed. For example,
      there exist many reports of false somatic mutations attributable entirely to the
      choice of analytic method. This pattern of mis-reporting may divert the
      investment of limiting resources for cancer research into fundamentally flawed
      directions. We provide here a review of the basic theoretic principles and
      observed patterns within the literature of solid tumors and inherited tumor
      susceptibility syndromes. These patterns provide support for a systematic
      approach to the critical analysis of the somatic mutation literature offered in
      the accompanying paper.

PMID- 16575205
TI  - Lentivirus-mediated gene therapy by suppressing survivin in BALB/c nude mice
      bearing oral squamous cell carcinoma.
AB  - Despite advances in surgery, radiotherapy, and chemotherapy, the long-term
      survival rates with oral squamous cell carcinoma (OSCC) have not significantly
      improved. Gene therapy for OSCC is currently under investigation in clinical
      trials. Lentivirus vector is considered to be a promising gene delivery tool, but
      their value in cancer gene therapy has not been studied thoroughly. Survivin is
      overexpressed in OSCC, making it a promising target for gene therapy. This study
      was conducted to determine whether lentivirus-mediated gene therapy by
      suppressing survivin could be exploited in the treatment of OSCC. A lentivirus
      vector encoding short hairpin RNA (shRNA) targeting survivin was constructed and
      transfected into KB cells in vitro. The results showed that survivin was
      persistently and markedly reduced by lentivirus-mediated RNA interference (RNAi);
      the growth of KB cells was decreased by 34.2% on day 5; the apoptosis rate
      induced by vincristine (VCR) was increased by 29.8% and caspase-3 activity was
      also significantly increased; the IC(50) value of adriamycin (ADM) were 0.09
      mug/ml, which indicated that survivin-knockout KB cells were 2.1 times more
      susceptible to ADM than the control; the clonogenic survival rate at 6 Gy of X
      ray was 3.7%, less than 15.3% of the control. In the xenograft model, the
      development of tumors as well as the growth of established tumors was inhibited
      by transfection of lentivirus. Our study indicates that lentivirus-mediated gene
      therapy is an attractive strategy in the treatment of OSCC and justifies the use
      of lentivirus in cancer gene therapy studies.

PMID- 16575207
TI  - Enhancement of DNA vaccine potency by sandwiching antigen-coding gene between
      secondary lymphoid tissue chemokine (SLC) and IgG Fc fragment genes.
AB  - DNA vaccine has become an attractive approach for generating antigen-specific
      immunity. Targeting antigens to FcRs for IgG (FcgammaRs) on dendritic cells (DCs)
      has been demonstrated to enhance antigen presentation. Secondary lymphoid tissue
      chemokine (SLC) has been shown to increase immune responses not only by promoting
      coclustering of T cells and DCs in the lymph nodes and spleen but also by
      regulating their immunogenic potential for the induction of T cell responses. In
      this study, using HPV 16 E7 as a model antigen, we constructed a chemotactic
      antigen plasmid DNA vaccine (pSLC-E7-Fc) by linking SLC and Fc gene sequences to
      each end of E7 and evaluated its potency of eliciting specific immune response.
      We found that immunization with pSLC-E7-Fc generated much stronger E7-specific
      lymphocyte proliferative and cytotoxic T lymphocyte (CTL) responses than control
      DNA. All the mice receiving pSLC-E7-Fc prophylactic vaccination remained tumor
      free upon subcutaneous inoculation of TC-1 cells, while those given control DNA
      all developed tumors. These tumor-free mice were also protected against TC-1
      rechallenge. Complete tumor regression with long-term survival occurred in 72% of
      mice given pSLC-E7-Fc as therapeutic vaccination. In experimental lung metastasis
      model wherein TC-1 cells were intravenously injected, therapeutic vaccination
      with pSLC-E7-Fc significantly reduced the number of tumor nodules in the lung. In
      vivo depletion with antibodies against CD4+or CD8+ T cells both resulted in
      complete abrogation of the pSLC-E7-Fc-induced immunotherapeutic effect. Our data
      indicate that the DNA vaccine constructed by the fusion of SLC and IgG Fc
      fragment genes to antigen-coding gene is an effective approach to induce potent
      anti-tumor immune response via both CD4+ and CD8+ T cells dependent pathways.

PMID- 16575209
TI  - Remembering team science is for the patients.

PMID- 16575208
TI  - Identification of overexpression of orphan G protein-coupled receptor GPR49 in
      human colon and ovarian primary tumors.
AB  - We used gene expression profiling to probe differences in transcriptional output
      between 15 panels of colon tumor and matched normal colon tissues. This analysis
      revealed that GPR49, an orphan G Protein-Coupled Receptor (GPCR) is overexpressed
      in 66% (10/15) colon tumors compared with normal colon tissues. Subsequent
      analysis of an additional 39 sets of matched normal and tumor colon tissues by
      real-time quantitative reverse transcriptase confirmed the upregulation of this
      receptor. The differential expression of GPR49 between normal and tumor tissue
      was significant (p > 0.001). GPR49 was upregulated in 25 of 39 (64%) colon
      primary tumor tissues. In addition to colon tumors, GPR49 was also found to be
      upregulated in 18 of 33 (53%) ovarian primary tumor tissues analyzed by RT-PCR.
      Moreover, the expression level of GPR49 in colon and ovarian tumors increased in
      more advanced tumors suggesting a role for the receptor in tumor progression. The
      selective overexpression of GPR49 in tumor tissues was further illustrated by
      specific immunohistochemical staining of colon and ovarian tumor tissues, a
      finding that correlates with the mRNA expression of the receptor. In addition,
      expression of GPR49 induced transformation in a ligand-dependent manner and
      Knockdown of GPR49 mRNA level induced apoptosis in colon tumor cells. These novel
      findings provide a foundation for further studies and suggest a potential role
      for GPR49 in tumorigenesis.

PMID- 16575210
TI  - Preclinical studies of bismuth-213 labeled plasminogen activator inhibitor type 2
      (PAI2) in a prostate cancer nude mouse xenograft model.
AB  - OBJECTIVES: The key objective of the study was to determine the single and
      multiple dose toxicity and efficacy of Bismuth-213 labeled PAI2 based targeted
      alpha therapy by selectively targeting uPA and uPAR in regressing prostate cancer
      in a nude mouse model. Targeted alpha therapy (TAT) is an experimental
      therapeutic modality for cancer. Another objective was to compare the in vivo
      pharmacokinetics using two different chelators to form the radioisotope-protein
      construct. METHODS: The single and multiple intra-peritoneal (IP) dose toxicity
      and efficacy of 213BiPAI2 was investigated in nude mice and its toxicity in
      rabbits. CD 31 staining for vasculature and uPA expression were measured at
      different stages of tumor growth. The pharmacokinetics of the chelators cDTPA and
      CHX-A'' were measured. RESULTS: All TAT regimes were well tolerated in mice and
      rabbits on biochemical and haematological examination. Capillaries became evident
      at six days post-cell inoculation. uPA expression was positive at all stages of
      tumour growth. No significant differences were observed between cDTPA and CHX-A.
      '' Inhibition of tumour growth was observed at 947 and 1421 MBq/kg single dose
      injection at three days post-PC3 cell inoculation. The three day post-inoculation
      multiple dose regime gave complete tumour growth inhibition at a total dose of
      947 MBq/kg given on five successive days. Mice treated at 6, 12 and 18 days post
      inoculation showed significantly slower tumour growth compared to controls.
      CONCLUSIONS: The efficacy of single and multiple dose TAT in mice was
      demonstrated within tolerance limits, the multiple dose regime being no more
      toxic than the single dose. Either of the two chelators could be used for 213Bi
      studies.

PMID- 16575211
TI  - Multiple-criterion evaluation of reported mutations: a proposed scoring system
      for the intragenic somatic mutation literature.
AB  - In an accompanying paper, we review the theoretical principles of tumor mutations
      and the observed patterns of mutations in the cancer literature. These patterns
      are discussed in the context of a perceived dichotomy in quality that exists
      among mutation reports. Due to the frequency of mis-reporting, a systematic
      approach to the somatic mutation literature in human cancer is needed. We propose
      a multiple-criterion numerical tool, referred to as the scoring SISTM (System for
      Intragenic Somatic Tumor Mutations), which effectively discriminates promising
      and unpromising somatic mutation reports in human cancer. Reports are assessed on
      12 criteria, and are given a final score of 15 or less. Scores in the range of 10
      to 15 are suggestive of well-presented reports of disease-inducing somatic
      mutations. Reports with scores less than 10 should be viewed with skepticism.

PMID- 16575213
TI  - Delayed diagnosis: the tuberculosis tragedy.

PMID- 16575231
TI  - Reprocessed single-use devices--safe or not?

PMID- 16575232
TI  - Beyond MRSA: VISA and VRSA: what will ward off these pathogens in health care
      facilities?

PMID- 16575236
TI  - Tahara.

PMID- 16575237
TI  - The bathing of older adults with dementia.
AB  - Older adults who need assistance with bathing often find the activity to be both
      physically and emotionally demanding, as do their caregivers. Research has
      identified several contributing factors, including pain; fatigue and weakness;
      confusion; anxiety resulting from being naked in front of strangers, being afraid
      of falling, and being in a noisy or unfamiliar place; and discomfort from cold or
      drafty bathing areas or harsh water sprays. The authors of this article make the
      case for the elimination of forced bathing. Research supports this change in
      philosophy and practice, whereby bathing is not a task to be performed but rather
      a human interaction. Inexpensive, practical, and evidence-based alternatives are
      discussed.

PMID- 16575239
TI  - Exercise and people with serious, persistent mental illness.

PMID- 16575240
TI  - Aortic dissection.

PMID- 16575241
TI  - How long and how much are nurses now working?
AB  - OBJECTIVE: Extended work schedules-those that vary from the standard eight hours
      per day, 35 to 40 hours per week-are common in nursing and contribute to problems
      with nursing recruitment and retention, in addition to compromising patient
      safety and the health and well-being of nurses. This study describes the nature
      and prevalence of such schedules across nursing settings. METHODS: Quantitative
      survey data collected as part of the Nurses Worklife and Health Study were
      analyzed. The sample consisted of 2,273 RNs. Demographic data, information about
      respondents' primary jobs (position, workplace, and specialty), and specific work
      schedule variables were analyzed, including data on off-shifts, breaks, overtime
      and on-call requirements, time off between shifts, and how often respondents
      worked more than 13 hours per day and on scheduled days off and vacation days.
      Respondents were also asked about activities outside of work, commuting time, and
      other non-nursing activities and chores. RESULTS: More than a quarter of the
      sample reported that they typically worked 12 or more hours per day, as did more
      than half of hospital staff nurses and more than a third of those with more than
      one job. A third of the total sample worked more than 40 hours per week, and more
      than a third worked six or more days in a row at least once in the preceding six
      months. Nearly a quarter rotated shifts. Almost one-quarter of nurses with more
      than one job worked 50 or more hours per week, and they were more likely to work
      many days consecutively, without sufficient rest between shifts, and during
      scheduled time off. Single parents were as likely as those with more than one job
      to work 13 to 15 hours per day, 50 to 60 hours or more per week, and many days
      consecutively. Seventeen percent of all nurses worked mandatory overtime, as did
      almost a quarter of the single parents. Nearly 40% of the total sample and more
      than 40% of hospital staff nurses had jobs with on-call requirements.
      CONCLUSIONS: The proportion of nurses who reported working schedules that exceed
      the recommendations of the Institute of Medicine should raise industry-wide
      concerns about fatigue and health risks to nurses as well as the safety of
      patients in their care.

PMID- 16575247
TI  - Is anybody listening? When will we get to real health care reform?

PMID- 16575248
TI  - Rx for medical marijuana? Interview by Susan Trossman.

PMID- 16575249
TI  - Adirondack Nurse: Going upcounty, where home care has many definitions. Interivew
      by Lori Soderlind.

PMID- 16575252
TI  - Health care workers and asthma.

PMID- 16575253
TI  - Stability of ADVATE, Antihemophilic Factor (Recombinant) Plasma/Albumin-Free
      Method, during simulated continuous infusion.
AB  - Continuous infusion of factor VIII (FVIII) concentrates during surgical
      procedures offers the potential for improved hemostatic control and reduced FVIII
      consumption, but requires stable FVIII concentrates. The stability of ADVATE,
      Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method (rAHF-PFM), was
      examined using various simulated conditions. Experiments performed with a multi
      therapy 6060 pump showed FVIII recoveries of 95% or more after 48 h for multiple
      lots of high-potency and mid-potency rAHF-PFM, with or without heparin. Non
      infused controls maintained at the same temperature showed similar FVIII
      recovery, demonstrating that the infusion system did not cause loss of FVIII
      activity. Supportive data generated using single lots of mid-potency or high
      potency rAHF-PFM infused through a MEDEX or HARVARD syringe pump, or a CADD Pump
      1, demonstrated FVIII recoveries of 83% or more at 24 or 48 h under all
      conditions tested. Additionally, rAHF-PFM was stable immediately after dilution
      in saline or saline/dextrose solutions, and after a 10-h exposure to ultraviolet
      and visible light. Taken together, these data demonstrate that rAHF-PFM is stable
      under conditions typically encountered during continuous infusion, and suggest
      that rAHF-PFM should be safe and effective when used for FVIII replacement by
      continuous infusion in patients with hemophilia A.

PMID- 16575254
TI  - Comparative expression profiling in primary and immortalized endothelial cells:
      changes in gene expression in response to hydroxy methylglutaryl-coenzyme A
      reductase inhibition.
AB  - Immortalized cell lines offer significant logistical advantages over primary
      cells when used for in-vitro studies. Immortalized cells may, however, exhibit
      important differences relative to their primary cell counterparts. In this study,
      microarrays were used to make a genome-wide comparison between primary human
      umbilical vein endothelial cells (HUVECs) and EA.hy926, an immortalized HUVEC
      cell line, in their baseline properties and in their response to inhibition of
      the mevalonate pathway with an inhibitor of hydroxy methylglutaryl-coenzyme A
      reductase (statin). HUVECs and EA.hy926 were incubated with control medium,
      atorvastatin, mevalonate, or a combination of atorvastatin and mevalonate for 24
      h. Gene expression profiles were obtained in duplicates using Affymetrix Human
      Genome U133A 2.0 arrays (Santa Clara, California, USA). Probe-sets were selected
      according to the following criteria: a twofold or greater increase/decrease in
      atorvastatin-treated cells compared with untreated cells; a twofold or greater
      reversal of the effect of atorvastatin by combined treatment with atorvastatin
      and mevalonate; no significant change in gene expression in cells treated with
      mevalonate alone compared with untreated cells. Most genes that were expressed by
      untreated HUVECs, were also expressed by untreated EA.hy926 cells. EA.hy926
      cells, however, constitutively expressed a large number of additional genes, many
      of which were related to cell cycle control and apoptosis. Atorvastatin induced
      differential expression (> or = twofold) of 103 genes in HUVECs (10 up, 93 down)
      and 466 genes in EA.hy926 cells (198 up, 268 down). Applying the above selection
      criteria, thrombomodulin and tissue plasminogen activator were up-regulated in
      both cell types, whereas, connective tissue growth factor, thrombospondin-1, and
      cysteine-rich angiogenic inducer 61 were down-regulated. In conclusion, EA.hy926
      cells retain most of the characteristics of endothelial cells under baseline
      conditions as well as after treatment with atorvastatin. It is necessary,
      however, to carefully select and validate changes in genes that are the focus of
      studies when using EA.hy926 cells. While this cell line is highly useful in
      studies on some genes, including genes encoding molecules involved in regulating
      thrombohemorrhagic homeostasis, they appear to be less suited for studies focused
      on other genes, particularly those involved in the regulation of cell
      proliferation and apoptosis.

PMID- 16575255
TI  - Influence of homocysteine on fibrin network lysis.
AB  - To elucidate some of the links between homocysteine and vascular disease, we have
      evaluated the effect of the amino acid on the formation (by kinetics studies),
      structure (by electron microscopy) and lysis of the fibrin network, using tissue
      type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u
      PA). We have studied whether homocysteine could alter the activity of the
      components involved in fibrinolysis (by amidolytic and thrombolytic methods). The
      results showed that homocysteine-associated networks were more compact and
      branched than controls (52 +/- 6 vs 44 +/- 5 fibers/field, P = 0.008), and were
      formed by shorter and thicker fibers. This clot proved to be more resistant to
      fibrinolysis with u-PA than control [lysis time 50%: 257 +/- 16 (homocysteine) vs
      187 +/- 6 min (control); P < 0.004], but there were no differences with t-PA.
      Homocysteine did not affect the biological activities of plasmin, or plasminogen
      activation by t-PA and u-PA. Defective fibrinolysis with u-PA was therefore
      associated with homocysteine-fibrin structural alterations rather than the
      homocysteine effect on the biological activities of the fibrinolytic components
      evaluated. Results suggest that hyperhomocysteinemic patients could produce tight
      clots, were more resistant to lysis, and generated a procoagulant environment in
      situ. We believe that our findings may contribute to understanding the mechanisms
      involved in the homocysteine harmful effect.

PMID- 16575256
TI  - Prolonged seated immobility-associated venous coagulability in a factor V Leiden
      heterozygote: a case-comparative study.
AB  - Prolonged sitting and thrombophilia may compound the risk of venous
      thromboembolism. In order to investigate suspected local lower limb venous
      procoagulant changes associated with prolonged sitting-induced venous stasis in a
      man heterozygous for factor V Leiden (participant X), we qualitatively compared
      venous coagulability in lower and upper limb plasma in this participant and three
      other male Caucasians over 8 h of sitting. Of the four participants, participant
      X had the highest baseline values of prothrombin fragments 1 and 2, thrombin
      antithrombin III complexes, tissue plasminogen activator, plasminogen activator
      inhibitor 1, D-dimer and soluble thrombomodulin. Over time, in participant X,
      venous prothrombin fragments 1 and 2, thrombin-antithrombin III complexes, and
      soluble thrombomodulin decreased in both limbs; D-dimer decreased in the lower
      limbs but increased in the upper limbs; the tissue plasminogen
      activator/plasminogen activator inhibitor 1 molar ratio increased in both limbs;
      and minimal changes were noted in haematocrit. A foot volume increase was
      associated with vague symptoms towards the end of the study. Overall, these
      changes were similar to those observed in other participants. It is concluded
      from this case comparison that prolonged sitting of 8 h duration under normal
      atmospheric conditions did not result in local, as well as systemic, procoagulant
      haemostatic responses in a heterozygote for factor V Leiden when compared with
      other healthy volunteers. However, this observed, possibly adaptive, response is
      more likely to be compromised in factor V Leiden subjects during continued or
      increased venous endothelial stress or in the presence of other venous
      thromboembolism risk factors.

PMID- 16575257
TI  - Functional characterization of fibrinogen Bicetre II: a gamma 308 Asn-->Lys
      mutation located near the fibrin D:D interaction sites.
AB  - The effects of the gamma-308 Asn-->Lys substitution of fibrinogen Bicetre II on
      clot formation, structure and properties were determined to elucidate the role of
      this part of the molecule in fibrin polymerization. This process was followed by
      measurement of turbidity, and the structure and biophysical characteristics of
      the clots were studied by permeation, scanning electron microscopy, and
      rheological techniques. Turbidity studies revealed an increased lag period and
      greater final turbidity for fibrin BII clots, indicating impaired oligomer
      formation. By permeation it was found that BII clots had greater network
      porosity, four times more than that of the control. The clot architecture
      visualized by scanning electron microscopy was similar to that of control clots
      with pore size and fiber diameter slightly increased. BII clots had a stiffness
      decreased by more than half, and an increased loss tangent, a measure of the
      inelastic deformation of the clot. All these results suggest a disruption of the
      proper alignment of fibrin monomers during oligomer formation. Consistent with
      these results, fibrin cross-linking by adding the physiological concentration of
      factor XIII to the purified protein showed that gamma and alpha chain cross
      linking was impaired in BII clots. This amino acid substitution defines
      distinctive effects on the surface of the D:D interaction sites that are
      reflected in the clot structure and functional properties.

PMID- 16575258
TI  - Gorog Thrombosis Test: analysis of factors influencing occlusive thrombus
      formation.
AB  - We used the Gorog Thrombosis Test to analyze the factors influencing the
      occlusion time, which represents platelet activation and subsequent occlusive
      thrombus formation, in 132 healthy Japanese volunteers (116 men, 16 women; mean
      age, 45.0 +/- 12.0 years). The Gorog Thrombosis Test was designed to evaluate
      platelet aggregation and thrombolytic activity under a high shear stress
      condition (175 dynes/cm) in a native blood sample in vitro. The mean +/- SD
      occlusion time was 154.8 +/- 64.7 s (men, 153.4 +/- 64.2 s and women, 165.4 +/-
      56.5 s). The occlusion time was inversely correlated with von Willebrand factor
      ristocetin cofactor activity (VWF:Rco) (r = -0.242, P = 0.0055) and von
      Willebrand factor antigen (r = -0.230, P = 0.0080). The mean occlusion time in
      the group with VWF:Rco of at least 170% (137 s) was significantly shorter than
      that in the group with VWF:Rco less than 170% (156 s, P < 0.05). Platelet counts,
      other coagulation markers and smoking showed no significant correlations with
      occlusion time. Red blood cells (r = -0.177, P = 0.0365), hemoglobin (r = -0.191,
      P = 0.0245) and hematocrit (r = -0.182, P = 0.0329) also showed inverse
      correlations with the occlusion time. This report is the first to clearly
      demonstrate the role of von Willebrand factor in the formation of occlusive
      thrombi in the Gorog Thrombosis Test.

PMID- 16575259
TI  - Budd-Chiari syndrome in a child due to a membranous web of the inferior vena cava
      resolved by systemic and local recombinant tissue plasminogen activator
      treatment.
AB  - Budd-Chiari syndrome is a heterogeneous group of disorders characterized by
      hepatic venous outflow obstruction. Although there are no guidelines for
      treatment of patients with Budd-Chiari syndrome, thrombolytic therapy may be
      useful in patients with acute Budd-Chiari syndrome. In this report, a boy with
      Budd-Chiari syndrome due to membranous obstruction of the inferior vena cava
      treated with systemic and local administration of recombinant tissue plasminogen
      activator is described. We would like to emphasize the role of systemic and local
      fibrinolytic treatment in these patients.

PMID- 16575260
TI  - The use of recombinant activated factor VII in the treatment of massive pulmonary
      hemorrhage in a preterm infant.
AB  - Pulmonary hemorrhage is a rare but well-known complication in preterm infants. We
      present a case of massive pulmonary hemorrhage in a 9-day-old male infant,
      successfully treated with intravenous recombinant activated factor VII (rFVIIa)
      (NovoSeven; Novo Nordisk). The infant was diagnosed with sepsis-related
      disseminated intravascular coagulation and required ventilator support for
      respiratory distress syndrome and blood transfusions due to active bleeding from
      endotracheal tube. After administration of the second dose of rFVIIa (120
      microg/kg per dose, every 2 h), the active bleeding subsided dramatically and a
      significant improvement in the oxygenation index was seen 8 h after the third
      dose of rFVIIa treatment. There were also significant improvements in the
      prothrombin time, International Normalized Ratio, activated partial
      thromboplastin time and plasma fibrinogen levels after the third dose of rFVIIa
      treatment. The infant was discharged on day 82 of life and there was no finding
      of thrombosis during the hospitalization period. At month 18 of follow-up, there
      was no morbidity related to the pulmonary and central nervous systems. This case
      suggests that rFVIIa is effective as an alternative therapy in controlling
      massive pulmonary hemorrhage of preterm infants.

PMID- 16575261
TI  - Antithrombin Nagasaki (Ser 116 to Pro): a rare antithrombin variant with abnormal
      heparin binding presenting during pregnancy.
AB  - Quantitative antithrombin deficiency constitutes an important risk factor for
      venous thromboembolism, stillbirth, and other complications of pregnancy. Studies
      suggest, however, that individuals heterozygous for missense mutations involving
      the heparin-binding site of antithrombin do not have a significantly increased
      thrombotic risk. Owing to the rarity of such mutations, it remains unclear
      whether any specific heparin-binding site defects might be associated with
      thrombotic potential. We report here the case of a pregnant woman with an
      exceptionally rare Type II heparin-binding site antithrombin variant. This case
      highlights the difficult issues that are associated with the management of Type
      II antithrombin deficiency during pregnancy.

PMID- 16575262
TI  - Influence of warfarin therapy on activated factor VII clotting activity.
AB  - Oral anticoagulant therapy has been widely employed to prevent and treat a
      variety of thrombotic disorders, although a new generation of antithrombotic
      drugs, which offer inhibition of clot-bound as well as fluid-phase thrombin, has
      been developed and tested in several clinical trials. Although most anticoagulant
      responses to hydroxycoumarin compounds are well established, there are
      controversial evidences on their influence on activated factor VII (FVIIa). After
      analyzing the prothrombin time (PT) (International Normalized Ratio reference
      range, 0.92-1.08), factor VII clotting activity (FVII:C) (reference range, 75-130
      U/dl) and activated factor VII clotting activity (FVIIa:C) (reference range, 30
      110 U/l) in 46 consecutive patients on stable warfarin therapy for atrial
      fibrillation, a consistent trend towards decreased values of both FVII:C and
      FVIIa:C was observed as PT values increased. At moderate-intensity
      anticoagulation, with international normalized ratios between 2 and 3, the mean
      activities of FVII:C and FVIIa:C dropped to 28 U/dl (range, 9-61 U/dl) and 5.8
      U/l (range, 1-18 U/l), respectively. Results of our investigations indicate that
      warfarin therapy decreases FVIIa:C, highlighting the potential benefits of oral
      anticoagulants in thrombotic disorders and other clinical conditions
      characterized by increased levels of FVIIa. Owing to the good correlation with
      FVIIa:C, we also hypothesize that the PT and/or FVII:C might be employed for
      monitoring recombinant FVIIa therapy.

PMID- 16575263
TI  - Limited usefulness of D-dimer in suspected deep vein thrombosis of the upper
      extremities.

PMID- 16575264
TI  - Recombinant activated factor VII in the management of massive obstetric bleeding.

PMID- 16575265
TI  - Leisure time physical activity, competitive sports and ischemic heart disease by
      Borjesson M. et al.

PMID- 16575266
TI  - ESC Study Group of Sports Cardiology: recommendations for participation in
      leisure-time physical activity and competitive sports for patients with ischaemic
      heart disease.
AB  - BACKGROUND: Evidence for the proper management of ischemic heart disease (IHD) in
      the general population is well established, but recommendations for physical
      activity and competitive sports in these patients are scarce. The aim of the
      present paper was to provide such recommendations to complement existing ESC and
      international guidelines on rehabilitation and primary/secondary prevention.
      DESIGN AND METHODS: Due to the lack of studies in this field, the current
      recommendations are the result of consensus among experts. Sports are classified
      into low/moderate/high dynamic and low/moderate/high static, respectively.
      RESULTS: Patients with a definitive IHD and higher probability of cardiac events
      are not eligible for competitive sports (CS) but for individually designed
      leisure time physical activity (LPA); patients with definitive IHD and lower
      probability of cardiac events as well as those with no IHD but with a positive
      exercise test and high risk profile (SCORE > 5%) are eligible for low/moderate
      static and low dynamic (IA-IIA) sports and individually designed LPA. Patients
      without IHD and a high risk profile+ a negative exercise-test and those with a
      low risk profile (SCORE < 5%) are allowed all LPA and competitive sports with a
      few exceptions. CONCLUSIONS: Individually designed LPA is possible and encouraged
      in patients with and without established IHD. Competitive sports may be
      restricted for patients with IHD, depending on the probability of cardiac events
      and the demands of the sport according to the current classification.

PMID- 16575267
TI  - Statement on cardiopulmonary exercise testing in chronic heart failure due to
      left ventricular dysfunction: recommendations for performance and interpretation.
      Part I: definition of cardiopulmonary exercise testing parameters for appropriate
      use in chronic heart failure.
AB  - Cardiopulmonary exercise testing (CPET) provides a global assessment of the
      integrated response to exercise involving the pulmonary, cardiovascular,
      haematopoietic, neuropsychological, and skeletal muscle systems. This information
      cannot be obtained through investigation of the individual organ systems in
      isolation. The non-invasive, dynamic physiological overview permits the
      evaluation of both submaximal and peak exercise responses, providing the
      physician with relevant information for clinical decision making. The use of CPET
      in management of the chronic heart failure patient is increasing with the
      understanding that resting pulmonary and cardiac function testing cannot reliably
      predict exercise performance and functional capacity and that, furthermore,
      overall health status and prognosis are predicted better by indices of exercise
      tolerance than by resting measurements. Our aim is to produce a statement which
      provides recommendations on the interpretation and clinical application of CPET
      in heart failure, based on contemporary scientific knowledge and technical
      advances: the focus is on clinical indications, issues of standardization, and
      interpretative strategies for CPET.

PMID- 16575268
TI  - Myocardial infarction and post-traumatic stress disorder: frequency, outcome, and
      atherosclerotic mechanisms.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) may develop in the aftermath of
      an acute myocardial infarction (MI). Whether PTSD is a risk factor for
      cardiovascular disease (CVD) is elusive. The biological mechanisms linking PTSD
      with atherosclerosis are unclear. DESIGN: A critical review of 31 studies in the
      English language pursuing three aims: (i) to estimate the prevalence of PTSD in
      post-MI patients; (ii) to investigate the association of PTSD with cardiovascular
      endpoints; and (iii) to search for low-grade systemic inflammatory changes in
      PTSD pertinent to atherosclerosis. METHODS: We located studies by PubMed
      electronic library search and through checking the bibliographies of these
      sources. RESULTS: The weighted prevalence of PTSD after MI was 14.7% (range 0
      25%; a total of 13 studies and 827 post-MI patients). Two studies reported a
      prospective association between PTSD and an increased risk of cardiovascular
      readmission in post-MI patients and of cardiovascular mortality in combat
      veterans, respectively. In a total of 11 studies, patients with PTSD had
      increased rates of physician-rated and self-reported cardiovascular diseases.
      Various cytokines and C-reactive protein were investigated in a total of seven
      studies suggesting that PTSD confers a pro-inflammatory state. CONCLUSIONS:
      Increasing evidence suggests that PTSD specifically related to MI develops
      considerably frequently in post-MI patients. More research is needed in larger
      cohorts applying a population design to substantiate findings suggesting PTSD is
      an atherogenic risk factor and to understand better the suspected behavioural and
      biological mechanisms involved.

PMID- 16575269
TI  - Long-term physical activity in leisure time and mortality from coronary heart
      disease, stroke, respiratory diseases, and cancer. The Copenhagen City Heart
      Study.
AB  - BACKGROUND: The purpose of this study was to describe the associations between
      different levels of long-term physical activity in leisure time and subsequent
      causes of deaths. DESIGN: The Copenhagen City Heart Study is a prospective
      cardiovascular population study of 19 329 men and women aged 20-93 in 1976.
      Physical activity in leisure time was estimated at the examinations in 1976-78
      and 1981-83. This analysis consists of 2136 healthy men and 2758 women aged 20-79
      years, with unchanged physical activity at the two examinations, and with all
      covariates included in the multivariate analyses: smoking, total-cholesterol,
      high-density lipoprotein-cholesterol, systolic blood pressure, diabetes mellitus,
      alcohol consumption, body mass index, education, income, and forced expiratory
      volume in 10.78 (% predicted). RESULTS: Adjusted relative risks (95% confidence
      interval) for coronary heart disease were, for moderate physical activity 0.71
      (0.51, 0.99) and for high 0.56 (0.38, 0.82). For cancer, moderate activity 0.77
      (0.61, 0.97) and high activity 0.73 (0.56, 0.95) and for all-cause mortality,
      moderate 0.78 (0.68, 0.89) and high 0.75 (0.64, 0.87) for both sexes combined.
      Using Kaplan-Meier plots we calculated gained years of expected lifetime from age
      50. Men with high physical activity survived 6.8 years longer, and men with
      moderate physical activity 4.9 years longer than sedentary men. For women the
      figures were 6.4 and 5.5 years, respectively. CONCLUSION: Long-term moderate or
      high physical activity was in both sexes associated with significantly lower
      mortality from coronary heart disease, cancer and all-causes. The same tendency
      was found for stroke and respiratory diseases, but the associations did not reach
      statistical significance.

PMID- 16575270
TI  - Combining serum biomarkers: the association of C-reactive protein, insulin
      sensitivity, and homocysteine with cardiovascular disease history in the general
      US population.
AB  - BACKGROUND: Elevated levels of serum biomarkers such as C-reactive protein (CRP)
      and homocysteine have been independently associated with cardiovascular risk.
      However, the prevalence of concurrent elevations of these biomarkers in the
      general population is unknown, as is their association with cardiovascular
      disease (CVD). METHODS: Data from adults (n = 4900) in the National Health and
      Nutrition Examination Survey were used to investigate the relationship between
      combinations of serum biomarkers of inflammation (CRP), atherosclerosis
      (homocysteine), and insulin sensitivity [homeostatic model assessment (HOMA)
      fasting insulin] and CVD. Using SUDAAN, logistic regression models were
      constructed to examine the relationships between elevated serum biomarkers (CRP,
      homocysteine, HOMA, or insulin), singly or in combination, and having a history
      of heart failure, myocardial infarction (MI), stroke, or any CVD, while
      controlling for age, race, sex, obesity, smoking, cholesterol level, diabetes
      history, hypertension history, exercise level, and dietary fiber intake. RESULTS:
      After adjustment for covariates, there was a significant relationship between
      concomitant elevations of CRP plus homocysteine and a history of MI [odds ratio
      (OR) 2.21], heart failure (OR 2.14), and any CVD (OR 1.87) that was stronger than
      the relationship between individual biomarkers alone and a history of CVD. In
      addition, combinations of elevated CRP plus HOMA and CRP plus insulin, remained
      significantly related to having a history of any CVD. CONCLUSION: Recent
      scientific evidence and the present findings demonstrate the possibility for
      improving cardiovascular risk stratification through the concurrent evaluation of
      multiple biomarkers. In particular, these findings demonstrate the need to
      evaluate the combination of CRP and homocysteine prospectively as predictors of
      CVD.

PMID- 16575271
TI  - Prognostic value of time-related changes of cardiopulmonary exercise testing
      indices in stable chronic heart failure: a pragmatic and operative scheme.
AB  - BACKGROUND: Although peak oxygen consumption (VO2) is an objective measurement of
      functional capacity linked to survival, most clinicians use clinical history to
      monitor changes over time of functional disability. The aim was to verify the
      prognostic value of time-related changes (Delta) of symptom-limited
      cardiopulmonary exercise testing (CPX) indices in stable chronic heart failure
      (CHF). DESIGN AND METHODS: We studied 231 stable CHF patients (200 men) with left
      ventricular ejection fraction (LVEF) of 24 +/- 8% and peak VO2 of 14.3 +/- 8
      ml/kg per min, who performed two symptom-limited CPX over time. RESULTS: The two
      incremental CPX were separated by a mean interval of 258 +/- 42 days; 59 (26%)
      suffered cardiovascular death or underwent urgent heart transplantation during
      the follow-up (1167 +/- 562 days). Peak VO2, LVEF (measured at second
      evaluation), Deltapeak VO2 and DeltaNYHA (New York Heart Association
      classification) were selected as independent predictors in the total population,
      and LVEF, Deltapeak VO2, and NYHA in patients with peak VO2 of 14 ml/kg per min
      or less (106 patients); no Delta parameter was selected in patients with
      preserved exercise tolerance. Survival analysis was performed taking into
      consideration the inter-test variability of peak VO2 (6%): true fall: more than
      6% decrease, decline within the measurement variability; less than 6% decrease,
      improvement within the measurement variability; less than 6% increase and true
      rise; more than 6% increase: total mortality rate was 51, 23, 19 and 14% (P <
      0.0001), respectively. CONCLUSIONS: Deltapeak VO2 is a useful outcome index; a
      combination of static (single) and time-related functional variables can enhance
      the prognostication process in stable CHF patients.

PMID- 16575272
TI  - Serum uric acid and long-term mortality from stroke, coronary heart disease and
      all causes.
AB  - BACKGROUND: Increased serum uric acid (SUA) levels are linked to obesity,
      dyslipidemia, diabetes and hypertension. Whether SUA carries a risk for coronary
      heart disease (CHD) and stroke remains uncertain. DESIGN: A prospective cohort
      study. METHODS: Of an original cohort of middle-aged workers who were examined in
      1963 and followed-up for 23 years, 9125 men, free of CHD at entry, are included
      in this study. Subjects were divided into quintiles according to baseline SUA
      levels. Hazard ratios (HR) for all-cause, CHD, and stroke mortality were
      estimated in SUA quintiles, with the third serving as a referent. RESULTS: During
      follow-up, 2893 deaths were recorded, including 830 ascribed to CHD and 292 to
      stroke. The HR for all death [1.22, 95% confidence interval (CI) 1.09-1.37] and
      CHD (1.29, 95% CI 1.05-1.58) were increased in the upper SUA quintile. Fatal
      stroke showed a U-shaped relationship as both the upper (HR 1.48, 95% CI 1.02
      2.17) and bottom (HR 1.43, 95% CI 0.99-2.08) quintiles were associated with a
      higher risk. Adjustment for confounders reduced the HR of the upper quintile for
      all outcomes, but did not attenuate the association of the bottom quintile with
      stroke (HR 1.52, 95% CI 1.04-2.23). When analysed separately by stroke type, the
      latter association seemed to be stronger for hemorrhagic (HR 3.27, 95% CI 1.14
      9.33) than for ischemic stroke (HR 1.34, 95% CI 0.87-2.05). CONCLUSION: In
      addition to findings supporting increased mortality among hyperuricemic subjects,
      we identified an association between low SUA levels and fatal stroke, which
      deserves further investigation.

PMID- 16575273
TI  - Depressive symptoms as risk factor of cardiovascular mortality in older European
      men: the Finland, Italy and Netherlands Elderly (FINE) study.
AB  - BACKGROUND: Depressive symptoms have been suggested to increase the risk of
      cardiovascular diseases, but this may reflect reversed causality. We investigated
      to what extent depressive symptoms are a true risk factor for cardiovascular
      mortality in elderly men. DESIGN: The Finland, Italy and Netherlands Elderly
      (FINE) study is a prospective cohort study conducted in Finland, Italy and The
      Netherlands. METHODS: Depressive symptoms were measured with the Zung self-rating
      Depression Scale in 799 elderly men, aged 70-90 years, free from cardiovascular
      diseases. Using Cox models, hazard ratios (HRs) were calculated for specific
      cardiovascular mortality endpoints. The analyses were adjusted for potential
      confounders, stratified on country and repeated after exclusion of men who died
      from cardiovascular diseases up to 5 years after baseline. RESULTS: During 10
      years of follow-up 224 (28%) men died from cardiovascular diseases. The adjusted
      hazard for a five-point increase in depressive symptoms was 1.15 [95% confidence
      interval (CI) 1.08-1.23] for cardiovascular mortality. This risk was stronger for
      mortality from stroke (HR 1.35; 95% CI 1.19-1.53) and heart failure (HR 1.16; 95%
      CI 1.00-1.35) in comparison with mortality from coronary heart disease (HR 1.08;
      95% CI 0.97-1.20) and other degenerative heart diseases (HR 1.06; 95% CI 0.91
      1.23). Exclusion of men who died from cardiovascular diseases within 5 years
      after baseline did not change the strength of the associations. There were no
      significant differences in HRs between northern and southern Europe. CONCLUSIONS:
      This study provides further and more convincing prospective evidence for
      depressive symptoms as a risk factor for cardiovascular mortality in elderly men.

PMID- 16575274
TI  - Cigarette smoking and risk of coronary heart disease incidence among middle-aged
      Japanese men and women: the JPHC Study Cohort I.
AB  - BACKGROUND: Few data have been available on the sex-specific magnitude of the
      smoking effect on the risk of coronary heart disease (CHD) in Asia. DESIGN AND
      METHODS: A population-based prospective cohort study of 19 782 men and 21 500
      women aged 40-59 years between 1990-1992 and 2001 was conducted to examine the
      relationship between smoking status and the risk of CHD. RESULTS: A total of 260
      incidences of CHD were confirmed among men, including 174 myocardial infarctions
      (MI). The numbers among women were 66 and 43, respectively. The multivariate
      relative risk [95% confidence interval (CI)] for current smokers versus never
      smokers in men after adjustment for cardiovascular risk factors, several life
      style factors and public health centre was 2.85 (1.98, 4.12) for total CHD and
      3.64 (2.27, 5.83) for MI. These respective risks in women were 3.07 (1.48, 6.40)
      and 2.90 (1.18, 7.18). Among men, a dose-dependent relationship was observed
      between the number of cigarettes and the risk of MI. The population-attributable
      risk per cent (95% CI) of CHD was 46% (34, 55) in men and 9% (0, 18) in women.
      Smoking cessation, however, led to a rapid decline in the CHD risk within 2
      years. CONCLUSION: Smoking raises the risk of CHD significantly in both sexes of
      middle-aged Japanese, with large public health significance especially in men.
      Smoking cessation would have an immediate effect on risk reduction.

PMID- 16575275
TI  - Effects of health counseling on behavioural risk factors in a high-risk
      cardiology outpatient population: a randomized clinical trial.
AB  - BACKGROUND: An evaluation study of an individual lifestyle advice intervention to
      reduce cardiovascular risk behaviours (high fat consumption, smoking, physical
      inactivity). METHODS: A randomized, controlled trial at the cardiology outpatient
      clinic of the University Hospital Maastricht. Participants were at high risk of
      incurring a cardiovascular event. Changes in risk behaviours and behavioural
      determinants were assessed with self-administered validated questionnaires.
      RESULTS: Questionnaires were completed by 1270 patients at baseline, 1169 after 4
      months (92%), and 1032 after 18 months (81.3%). After 4 months, intention-to
      treat analyses revealed a decrease in fat consumption (-5.6%, P = 0.000), a
      reduction in the percentage of smokers [odds ratio (OR) 0.57, 95% confidence
      intervals (CI) 0.33-0.97] and a trend towards a maintained physical activity
      level (OR 1.28, 95% CI 0.97-1.70). No long-term effects were found. CONCLUSION:
      The lifestyle advice intervention was potentially effective in changing
      cardiovascular risk behaviours, but should be further improved to be effective in
      secondary cardiovascular prevention. The main limitations of the study were
      related to the randomization procedure and the self-selection of patients and
      cardiologists.

PMID- 16575276
TI  - Counselling overweight and obese patients in primary care: a prospective cohort
      study.
AB  - BACKGROUND: Primary care physicians are well positioned to provide counselling
      for overweight and obese patients, but no prospective study has assessed the
      effectiveness of this counselling in primary care. We aimed to evaluate weight
      reduction counselling by primary care physicians, and its relationship with
      weight change and patients' behaviour to control weight. DESIGN: A prospective
      cohort study. METHODS: We enrolled 523 consecutive overweight and obese patients
      from two Swiss academic primary care clinics. Physicians and patients were
      blinded to the study aims. We assessed the use of 10 predefined counselling
      strategies for weight reduction, and weight change and behaviour to control
      weight after 1 year. RESULTS: Sixty-five per cent of patients received some form
      of weight reduction counselling whereas 35% received no counselling. A total of
      407 patients completed the 1-year follow-up. Those who received counselling lost
      on average (SD) 1.0 (5.0) kg after 1 year, whereas those who were not advised
      gained 0.3 (5.0) kg (P = 0.02). In multivariate analysis, each additional
      counselling strategy was associated with a mean weight loss of 0.2 kg (95%
      confidence interval 0.03-0.4, P = 0.02). Patients counselled by their physician
      had more favourable behaviour to control weight than those not counselled, such
      as setting a target weight (56 versus 36%) or visiting a dietician (23 versus
      10%, both P < 0.001). CONCLUSIONS: Weight reduction counselling by primary care
      physicians is associated with a modest weight loss and favourable behaviour to
      control weight. However, many obese and overweight patients receive no advice on
      weight loss during primary care visits.

PMID- 16575277
TI  - Household cardiovascular screening of high-risk families: a school-based study.
AB  - BACKGROUND: A parental history of cardiovascular disease has a strong
      relationship with risk factor clusters in the offspring. This study was performed
      to identify major cardiovascular risk factors in middle school-aged children and
      their parents in both high and low-risk families. DESIGN: A school-based, cross
      sectional study. METHODS: The middle schools of the 6th district of Tehran were
      divided randomly into two groups. A total of 169 high-risk children with their
      families were recruited from the first group and 105 low-risk children with their
      families were recruited from the second group of schools. Anthropometric and
      metabolic measurements were performed. RESULTS: The means of the waist
      circumference and waist-to-hip ratio were significantly higher in high-risk
      fathers. The means of total and low-density lipoprotein (LDL) cholesterol were
      significantly higher in both parents and children of the high-risk group. The
      means of the fasting plasma glucose were significantly higher in fathers and
      offspring of high-risk families. More fathers in high-risk families were smokers.
      The prevalence of increased total cholesterol, LDL-cholesterol and hyperglycemia
      (> or = 100 mg/dl) were higher in high-risk parents and children. The prevalence
      of increased body mass index (> or = 25 kg/m for parents and 85th percentile for
      children) was higher in fathers and children of high-risk families. CONCLUSIONS:
      Cardiovascular risk factors are more prevalent and clustered in high-risk
      families. The screening of high-risk families is essential to prevent the
      progression of atherosclerosis from childhood and reduce the burden of
      cardiovascular disease in adulthood.

PMID- 16575278
TI  - Arterial wave reflection is associated with severity of extracoronary
      atherosclerosis in patients with coronary artery disease.
AB  - BACKGROUND: Arterial wave reflection is a major determinant of left ventricular
      function, coronary perfusion and cardiovascular risk. We investigated whether
      arterial wave reflection may detect atherosclerosis of peripheral arteries in
      patients with documented coronary artery disease (CAD). METHODS: Radial artery
      applanation tonometry and pulse wave analysis was performed in 184 patients with
      documented CAD at coronary angiography; central blood pressures and augmentation
      index (AI) were measured. Ankle-brachial (ABI) index and intima-media thickness
      (IMT) were used as indices of atherosclerosis of the lower limbs and the carotid
      arteries respectively. RESULTS: Patients with abnormal IMT (> 0.7 mm, first
      tertile) or ABI (< 0.94, first tertile) had higher AI than patients with lower
      IMT or higher ABI (24 +/- 17 versus 17 +/- 16% and 23 +/- 18 versus 18 +/- 13%,
      respectively, P < 0.05). In multivariate analysis, increasing AI was associated
      with age, female gender, heart rate, mean blood pressure, hyperlipidaemia, and
      use of statins (regression coefficient (beta) = 0.50, beta = 0.15, beta = -0.60,
      beta = 0.23, beta = 0.16 and beta = -0.14, respectively, P < 0.05). Increasing AI
      was associated with an adjusted-odds ratio of 1.035 [95% confidence interval
      (CI), 1.005-1.066], P = 0.02 for an abnormal IMT and of 1.08 (95% CI, 1.024
      1.146), P = 0.005 for ABI after adjustment for age, gender, heart rate, height,
      blood pressure, atherosclerotic risk factors, obesity and medication. No relation
      was found between AI and Gensini score or for the number of diseased coronary
      vessels. CONCLUSION: Augmentation index is a marker of extensive extracoronary
      atherosclerosis in patients with CAD.

PMID- 16575279
TI  - Relationship of smoking and smoking cessation with ankle-to-arm blood pressure
      index in elderly Japanese men.
AB  - BACKGROUND: Cigarette smoking is associated with an increased risk of peripheral
      arterial disease, but the relationship between smoking cessation and preclinical
      peripheral atherosclerosis is uncertain. DESIGN AND METHODS: A cross-sectional,
      population-based study to examine the effect of smoking and smoking cessation on
      the prevalence of peripheral arterial disease among 1215 men aged 60-79 years in
      two Japanese communities in 1999-2000. The ankle-to-arm systolic blood pressure
      index (AAI) was used as an estimate of the presence of peripheral
      atherosclerosis. RESULTS: The mean AAI correlated inversely and linearly with
      smoking status and pack-years of smoking. The multivariate prevalence odds ratio
      [95% confidence interval (CI)] of low AAI (< 0.90) compared with never-smokers
      was 3.7 (95% CI 1.1-12.7) for current smokers and 4.2 (95% CI 1.2-14.6) for men
      with 45 or more pack-years of smoking. In men who have quit smoking for 20 years
      or more, the mean AAI was higher and the prevalence of low AAI (< 0.90) was lower
      than those of current smokers, but similar to those of never-smokers.
      CONCLUSIONS: Our results confirm that current smoking and pack-years of smoking
      correlate with the presence of peripheral artery disease. The results suggest
      that smoking cessation for 20 years or more is associated with the regression of
      atherosclerosis in peripheral arteries. This finding needs to be confirmed by a
      prospective study.

PMID- 16575280
TI  - Cardiopulmonary evidence of exercise-induced silent ischaemia.
AB  - BACKGROUND: Exercise-induced ST changes, suggestive of cardiac ischaemia, are
      found in asymptomatic patients. METHODS: Gas exchange kinetics were studied
      during exercise to help to separate patients affected by epicardial coronary
      disease from those without. Forty-eight patients, without angina symptoms and
      showing significant changes of ST during exercise, underwent a coronarography and
      maximal cardiopulmonary exercise test. Thirty-five healthy individuals of matched
      age and sex underwent a cardiopulmonary exercise test as controls. RESULTS:
      Patients were grouped according to the presence (group 1, n = 35) or the absence
      (group 2, n = 13) of significant coronary lesions at angiography. When corrected
      for predicted oxygen consumption (VO2) at peak exercise and at anaerobic
      threshold, results showed a low VO2 at peak exercise and anaerobic threshold in
      group 1 (68 +/- 19 and 84 +/- 17% of predicted, respectively) compared with
      normal subjects (91 +/- 19 and 96 +/- 24% of predicted VO2) and group 2 patients
      (86 +/- 17 and 96 +/- 18%). Also the ischaemic threshold, when normalized for
      predicted workload at peak exercise, occurred earlier in group 1 (67 +/- 22%)
      than in group 2 (87 +/- 19%). The time-related (Delta)VO2/Deltawork relationship
      showed a significant flattening above the anaerobic threshold in group 1 (7.4+/
      2.2 versus 9.4+/-1.4 ml/watt per minute, P < 0.01), but not in controls or in
      group 2. Also the DeltaVO2/Deltawork relationship, above the ischaemic threshold,
      flattened in group 1, but not in group 2. CONCLUSION: The suggestion of major
      coronary disease in patients with exercise-induced ST changes is given by: (i) a
      flattening of the DeltaVO2/Deltawork relationship, above both the ischaemic and
      anaerobic thresholds; and (ii) low VO2 values at anaerobic and ischaemic
      thresholds.

PMID- 16575281
TI  - Physical activity and negative emotional response after percutaneous coronary
      intervention.
AB  - BACKGROUND: The aims of this study were to investigate the association between
      negative emotional response (NER) and physical activity levels in percutaneous
      coronary intervention (PCI) patients, and to examine the extent to which physical
      activity levels were influenced by factors such as the patients' age, sex, and
      attendance at a cardiac rehabilitation (CR) programme. METHODS: A consecutive
      series of 200 PCI patients [mean age 59.0 (+/-10.1) years] completed telephone
      interviews 2 weeks and 6 months after their procedure. NER was assessed using 12
      items addressing patients' perceptions and concerns regarding symptoms, diagnosis
      and prognosis. Physical activity was assessed by asking four questions relating
      to the frequency and duration of walking and of moderate activity. CR attendance,
      medical history and sociodemographic data were also collected. Hierarchical
      linear regression was used to assess the association between NER and physical
      activity over time. RESULTS: After controlling for baseline levels of moderate
      activity and other covariates, NER significantly predicted change in moderate
      activity over 6 months. Only baseline walking levels predicted the duration and
      frequency of walking at 6 months. CONCLUSION: NER can be considered an inhibitive
      factor towards increased moderate activity uptake after PCI. Walking after PCI
      does not appear to be affected by NER. These findings highlight the need to focus
      on improving the emotional aspects of patients' recovery.

PMID- 16575282
TI  - Increased absenteeism from work among aware and treated hypertensive and
      hypercholesterolaemic patients.
AB  - AIM: The 'labelling hypothesis' was introduced on the basis of the observation
      that labelling subjects with blood pressure elevation as hypertensive was
      associated with an increase in sickness absence. In the Belstress I study this
      hypothesis was analysed in the same way for the possible influence on sick leave
      of labelling persons with elevated cholesterol as hypercholesterolaemic. METHODS
      AND RESULTS: The Belstress I cohort concerns a sample of more than 16,000 men and
      5,000 women at work in 24 Belgian industries in various sectors. Baseline data
      were collected by questionnaire and clinical examination. Awareness was defined
      as answering positively to the question 'did a physician ever tell you that your
      blood pressure/serum cholesterol was too high?' Sick leave data were
      independently and objectively recorded during 1 year following the screening.
      Sick leave was treated in a dichotomous way whereby the event was defined as
      being in the highest quartile of the annual number of days of sick leave (10 days
      or more for men and 15 days or more for women) or as being in the highest
      quartile of the annual number of spells of sick leave (two spells or more for
      both sexes). Gender-specific logistic regression analyses were performed, with
      adjustment for a large set of covariates. A positive association was observed
      between both awareness of hypertension and awareness of hypercholesterolaemia and
      the various definitions of sick leave, in both sexes and after adjustment for
      different covariates. When dividing up aware subjects into treated versus
      untreated, we observed in men the highest sick leave incidence in aware and
      treated hypertensive patients as well as in aware and treated
      hypercholesterolaemic patients. In women findings were less consistent, probably
      due to the smaller sample size. When looking at cumulative effects by examining
      participants with both hypertension and hypercholesterolaemia and their level of
      awareness for one or both risk factors, a statistically significant gradient was
      noticed in men, with the highest sick leave incidence, whatever the definition,
      in men aware for both risk factors, followed by men aware for one. In women the
      same trends were observed, but no level of statistical significance was reached.
      CONCLUSION: Without being able to test the effect of 'labelling' as such, our
      study provides support for the association between awareness of two different
      coronary risk factors and incidence of sick leave. Probably a common mechanism is
      at the base of these findings. Further research is needed, in order to reduce
      potential negative effects of screening on human wellbeing as well as on
      productivity.

PMID- 16575283
TI  - Coffee and myocardial infarction: heterogeneity of an association in Portuguese
      men.
AB  - BACKGROUND: Despite the amount of published studies on the subject, controversy
      still exists about the effect of coffee drinking on the occurrence of coronary
      heart disease. In general, epidemiological studies do not support the belief that
      it is a major risk factor. DESIGN: A community-based case-control study was
      conducted. METHODS: A random sample of men aged 40 years and over with no
      previous myocardial infarction was compared with patients with a first acute
      myocardial infarction (AMI). A structured questionnaire was used to collect
      information on sociodemographic characteristics, personal and family medical
      history and lifestyles. Dietary data were obtained by a food frequency
      questionnaire. Odds ratios were calculated by unconditional logistic regression.
      After exclusions, 290 cases and 364 controls were considered in the final
      analysis. RESULTS: Coffee drinking is a widespread habit in this population, and
      most individuals did not change their habit throughout life. Most participants
      reported the consumption of moderate amounts of coffee (< 25% drank more than
      four cups a day) and espresso was by far the most commonly used brewing. The
      crude odds ratio for having ever drunk coffee regularly was 0.5 (95% confidence
      interval 0.3-1.1). However, there was a significant effect-measure modification
      by family history of AMI (P = 0.02). CONCLUSIONS: The results suggest different
      susceptibility to coffee drinking, such that coffee drinking was positively
      although not significantly associated with an increased risk of AMI in men with a
      family history of AMI, whereas there was a significant inverse association with
      the occurrence of myocardial infarction among men with no family history of AMI.

PMID- 16575284
TI  - Cost effectiveness of a smoking cessation program in patients admitted for
      coronary heart disease.
AB  - BACKGROUND: Smoking cessation is probably the most important action to reduce
      mortality after a coronary event. Smoking cessation programs are not widely
      implemented in patients with coronary heart disease, however, possibly because
      they are thought not to be worth their costs. Our objectives were to estimate the
      cost effectiveness of a smoking cessation program, and to compare it with other
      treatment modalities in cardiovascular medicine. METHODS: A cost-effectiveness
      analysis was performed on the basis of a recently conducted randomized smoking
      cessation intervention trial in patients admitted for coronary heart disease. The
      cost per life year gained by the smoking cessation program was derived from the
      resources necessary to implement the program, the number needed to treat to get
      one additional quitter from the program, and the years of life gained if quitting
      smoking. The cost effectiveness was estimated in a low-risk group (i.e. patients
      with stable coronary heart disease) and a high-risk group (i.e. patients after
      myocardial infarction or unstable angina), using survival data from previously
      published investigations, and with life-time extrapolation of the survival curves
      by survival function modeling. RESULTS: In a lifetime perspective, the
      incremental cost per year of life gained by the smoking cessation program was
      euro 280 and euro 110 in the low and high-risk group, respectively (2000 prices).
      These costs compare favorably to other treatment modalities in patients with
      coronary heart disease, being approximately 1/25 the cost of both statins in the
      low-risk group and angiotensin-converting enzyme inhibitors in the high-risk
      group. In a sensitivity analysis, the costs remained low in a wide range of
      assumptions. CONCLUSIONS: A nurse-led smoking cessation program with several
      months of intervention is very cost-effective compared with other treatment
      modalities in patients with coronary heart disease.

PMID- 16575286
TI  - Soy products and risk of an aneurysmal rupture subarachnoid hemorrhage in Japan.
AB  - BACKGROUND: The aim of this study was to explore the relationship between soy
      products and the risk of subarachnoid hemorrhage in a case-control study. DESIGN:
      A case-control study was conducted. METHODS: Incident subarachnoid hemorrhage
      cases (n = 201) were identified and individually matched on age (+/- 2 years) and
      sex to community (n = 201) controls from April 1992 to March 1997. A factor
      analysis was conducted to identify dietary patterns in relation to subarachnoid
      hemorrhage risk. RESULTS: Soy-rich products were significantly associated with a
      decreased risk of subarachnoid hemorrhage (lowest versus highest quartile,
      adjusted odds ratio 0.46; 95% confidence interval 0.18-0.88). CONCLUSION: The
      findings suggest that a diet high in soy products may be protective against the
      development of subarachnoid hemorrhage.

PMID- 16575285
TI  - Preterm delivery of a first child and subsequent mothers' risk of ischaemic heart
      disease: a nested case-control study.
AB  - Several studies have suggested that preterm delivery is related to a risk of
      subsequent ischaemic heart disease (IHD) in the mother. We conducted a nested
      case-control study in the E3N cohort to assess the association between preterm
      delivery of a first child and IHD, and the effect of major cardiovascular risk
      factors on this association. The study included 109 cases and 395 controls.
      Mothers who had preterm delivery were at an increased risk of IHD [multivariate
      hazard ratio 2.09 (95% confidence interval 1.07-4.09)]. This association was
      independent of major cardiovascular risk factors.

PMID- 16575290
TI  - Increased cell opening and prolapse of struts of a neuroform stent in curved
      vasculature: value of angiographic computed tomography: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: To describe the use of a new imaging tool, angiographic
      computed tomography, for visualization of cell opening and strut prolapse of a
      Neuroform 2 stent (Boston Scientific/Target, Fremont, CA) placed in curved
      vasculature for treatment of a basilar tip aneurysm. CLINICAL PRESENTATION: A 46
      year-old woman presented with an unruptured 8-mm basilar tip aneurysm with a wide
      patulous neck. INTERVENTION: A 4 x 20-mm Neuroform 2 stent was placed across the
      aneurysm neck. Angiographic computed tomographic scanning was performed using a
      flat detector biplane angiographic system with new commercially available
      software (Dyna-CT; Siemens Medical Solution, Forchheim, Germany) and the
      following parameters: 20-second acquisition, 0.4-degree increment, 512 matrix in
      projections, 220-degree total angle, 20 degree/s, and approximately 15 to 30
      frames/s, for a total of 538 projections. Image postprocessing was performed to
      correct scattered radiation, beam hardening, and ring artifacts on a commercially
      available workstation (Leonardo, Siemens Medical Solutions, Erlangen, Germany).
      The aneurysm was coiled in a second session, using bare platinum coils without
      clinical sequelae. CONCLUSION: Increased opening of cells and prolapsing of
      struts of an open cell design stent can occur after placement in a curved vessel
      across an aneurysm orifice. Angiographic computed tomography is a new imaging
      tool that provides visualization of intracranial stents that is superior to
      digital subtraction angiogram or nonsubtracted images. It will enhance our
      understanding of stent behavior in clinical practice and improve the efficacy and
      safety of intracranial stent placement. Further in vitro and in vivo imaging
      studies of intracranial stents are necessary to assess the value of this
      promising new technique.

PMID- 16575291
TI  - Surgical management of distal coil migration and arterial perforation after
      attempted coil embolization of a ruptured ophthalmic artery aneurysm: technical
      case report.
AB  - OBJECTIVE AND IMPORTANCE: Distal coil migration is a rare but hazardous
      complication of aneurysm coil embolization. Various microsnare devices have been
      developed to address this problem. We describe the surgical management of a case
      in which microsnare retrieval failed. CLINICAL PRESENTATION: A 34-year-old woman
      presented with subarachnoid hemorrhage. Magnetic resonance imaging, computed
      tomography angiography, and conventional angiography showed an approximately 2.5
      mm ophthalmic artery aneurysm. Using balloon remodeling, a 2 x 4-cm coil was
      deployed into the aneurysm fundus. While the coil pusher was being removed after
      deployment, the microcatheter advanced abruptly into the aneurysm. The coil mass
      was dislodged and migrated into the angular branch of the middle cerebral artery.
      Contrast extravasation was noted during attempted retrieval with a microsnare
      device. TECHNIQUE: Computed tomographic scans showed a subarachnoid hemorrhage in
      the territory of the left frontotemporal operculum. A left modified
      orbitozygomatic approach was performed. The coil mass was removed from the
      angular artery and a thromboembolectomy was performed. The artery was repaired
      and the pseudoaneurysm was clip ligated. The ophthalmic artery aneurysm was clip
      ligated. The patient recovered without deficits. CONCLUSION: Distal coil
      migration and arterial perforation can be treated surgically with a good clinical
      outcome.

PMID- 16575292
TI  - Simultaneous image-guided and endoscopic navigation without rigid cranial
      fixation: application in infants: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Infants and young children demonstrate a variety of
      intraventricular and periventricular lesions. Endoscopy has proven useful in the
      treatment of many of these lesions, but its benefit is limited if it is applied
      to complex loculated cysts or if the disease is concealed by normal ependymal
      boundaries. In adults and older children, endoscopy can be augmented by the
      simultaneous use of frameless stereotaxy, but this combined modality has not been
      possible in infants and young children without rigid cranial fixation. We
      describe a method of achieving simultaneous stereotactic and endoscopic
      navigation in infants and young children by using a pinless, frameless
      stereotactic assembly. CLINICAL PRESENTATION: The first patient was a 6-week-old
      boy with macrocephaly and a bulging fontanelle. Computed tomographic and magnetic
      resonance imaging revealed a complex arachnoid cyst and obstructive
      hydrocephalus. The second patient was a 7-month-old, ex-premature (27-wk
      gestational age) boy who developed posthemorrhagic hydrocephalus. He underwent
      multiple shunt revisions, one of which was complicated by enterococcal
      ventriculitis. Despite bilateral ventriculoperitoneal shunts, he developed
      increasing head circumference, listlessness, and irritability. Imaging revealed
      an enlarged, multiloculated, and asymmetric ventricular system. INTERVENTION:
      Simultaneous image-guided and endoscopic neuronavigation was implemented in both
      patients. Before the procedure, a cranial reference arc was secured to the outer
      table of the cranium through a small incision adjacent to the operative field.
      After the stereotactic apparatus was registered, the software was used to plan a
      trajectory for the approach. A burr hole was then made, and a rigid 6-mm
      endoscope was inserted for direct visualization. Once advanced past the
      endoscopic port tip, the electromagnetic coil stylet was used to stereotactically
      track position and identify areas for fenestration, biopsy, and catheter
      insertion. CONCLUSION: Endoscopic views of complex hydrocephalus and arachnoid
      cysts alone are often difficult to interpret. Simultaneous image-guided and
      endoscopic neuronavigation may be advantageous in the management of complex cases
      that are anatomically related to the ventricular system in infants for whom rigid
      cranial fixation could lead to increased procedure-related morbidity.

PMID- 16575293
TI  - Use of allogeneic skin graft for the closure of large meningomyeloceles:
      technical case report.
AB  - OBJECTIVE AND IMPORTANCE: To describe an alternative approach to the operative
      management of large meningomyeloceles, in which primary closure is not possible.
      CLINICAL PRESENTATION: Two full-term infants presented with very large
      meningomyeloceles for closure after an uncomplicated delivery. TECHNIQUE: An
      allogeneic skin graft was used in both cases to approximate the skin defect that
      remained after removal of the large meningomyelocele sacs. The surgical site was
      treated with dressing changes only during the postoperative period. CONCLUSION:
      The independent use of allogeneic skin grafts can lead to a successful cosmetic
      result for the treatment of large meningomyeloceles without the use of
      complicated skin incisions or flap advancements.

PMID- 16575294
TI  - Minimally invasive atlantoaxial fixation with a polyaxial screw-rod construct:
      technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Posterior C1-C2 fusion with polyaxial screw and rod
      fixation has become an accepted means of atlanto-axial stabilization. We describe
      a novel technique for minimally invasive placement of C1 lateral mass screws and
      C2 pedicle screws for polyaxial screw-rod stabilization. CLINICAL PRESENTATION:
      The patient presented with a history of chronic neck pain, as well as a 6-month
      history of weakness and paresthesias involving her left hand. An Os Odontoideum
      was present on computed tomographic imaging of the cervical spine. Significant
      instability was noted on flexion-extension imaging, and magnetic resonance
      imaging demonstrated mild T2 signal change within the spinal cord. TECHNIQUE:
      Under fluoroscopic guidance, serial dilators were passed through a 2.5 cm
      paramedian skin incision to allow placement of an expandable tubular retractor.
      The exposure was centered on the C2 lateral mass. After expansion of the
      retractor and further subperiosteal dissection, the C1 and C2 lateral masses were
      visible permitting placement of a polyaxial screw rod construct. This procedure
      was carried out bilaterally. CONCLUSION: Placement of C1 lateral mass and C2
      pedicle screws using minimally invasive techniques is technically feasible.

PMID- 16575295
TI  - two-stage operation for resection of spinal cord astrocytomas: technical case
      report of three cases.
AB  - OBJECTIVE AND IMPORTANCE: Surgery for excision of intramedullary spinal cord
      tumors without increasing neurological deficit is one of the more difficult
      operations in spinal surgery. In particular, infiltrating astrocytomas without a
      clear cleavage between the tumor and normal spinal cord parenchyma are difficult
      to remove totally without producing additional neurological impairment. In this
      study, we describe a two-stage resection facilitating total resection of
      intramedullary tumors. CLINICAL PRESENTATION: Three cases of spinal cord
      astrocytomas were treated using a two-staged method. TECHNIQUE: The first surgery
      included myelotomy, biopsy and duroplasty. A thin expanded
      polytetrafluoroethylene sheet was placed between the dorsal surface of the spinal
      cord and dura mater to prevent adhesions. Two or 3 weeks after surgery, a second
      surgery was performed to remove the now exophytic tumor. RESULTS: Magnetic
      resonance imaging scans showed exophytic extrusion of the tumor in all three
      cases before the second operation. In each patient, we were able to carry out
      gross total removal of the tumors without additional neurological deficit except
      for transient joint position sense loss in one case. All three patients remain
      neurologically stable without evidence of tumor recurrence more than 3 years
      after surgery. CONCLUSION: A two-stage operation may enhance the surgeon's
      ability to completely resect extensive low-grade spinal cord astrocytomas and, at
      the same time preserve neurological function.

PMID- 16575296
TI  - Giant eccrine adenocarcinoma of the scalp with intracranial invasion: resection
      and reconstruction using a vacuum-assisted closure device: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Carcinoma of the adnexal structures of the skin is a
      rare malignancy, and is even more unusual in the scalp. We report an unusual case
      of scalp adnexal carcinoma of eccrine origin that went untreated for years,
      resulting in a giant tumor with extension through the cranium. The tumor
      resection and reconstruction of the cranium and scalp defects posed unique
      challenges. CLINICAL PRESENTATION: A 54-year-old woman experienced a large
      recurrence of her scalp adnexal carcinoma after an incomplete wide local
      excision, which invaded through the cranium. INTERVENTION: The entire vertex of
      the scalp and cranium were removed en bloc. After cranioplasty, a free
      vascularized muscle flap was used for soft tissue coverage, but failed owing to
      poor vascular inflow. A large area of dura was left open, using a vacuum-assisted
      wound closure device to generate granulation tissue by secondary intention.
      Another split thickness skin graft was used to provide a cosmetically acceptable
      outcome. CONCLUSION: Scalp adnexal tumors of eccrine origin rarely metastasize
      and can be resected for cure with complete removal. Reconstruction options for
      large scalp and cranial tumors may be limited, and allowing the dura to granulate
      by secondary intention has been very rarely described. The novel use of a vacuum
      assisted wound closure device was a very useful adjunct in this situation, and
      may be beneficial in the reconstruction of other patients with large scalp and
      cranial defects after neurosurgical procedures. It should be used with caution,
      since it may risk injury to a major venous sinus, especially when used in the
      midline, or cerebrospinal fluid leakage.

PMID- 16575297
TI  - Parenchymal perianeurysmal cyst in the brain: case report.
AB  - OBJECTIVE AND IMPORTANCE: Parenchymal perianeurysmal cysts are rare, and only
      seven cases have been reported. We present a case report with a 30 month follow
      up on this topic. The possible etiopathogenetic mechanisms of cyst formation are
      discussed. CLINICAL PRESENTATION: A 54-year-old man with a 5-month history of
      headache and a computed tomography scan showing a giant parenchymal cyst located
      in the right temporal lobe with a mural enhanced nodule was admitted to our
      neurosurgical department with the diagnosis of cystic brain tumor. Magnetic
      resonance imaging followed by digital subtraction angiography identified the
      enhancing nodule as a large right middle cerebral artery aneurysm. INTERVENTION:
      Surgical treatment was performed; the aneurysm was clipped and the cyst
      evacuated. Postoperative digital subtraction angiography confirmed the clipping
      of the aneurysm at the neck. Serial magnetic resonance imaging controls showed
      the permanent collapse of the cyst. CONCLUSION: Parenchymal perianeurysmal cysts
      are rare. In the presence of parenchymal cysts neighboring main vessels, the
      possibility of a perianeurysmal cyst should be considered. In regard to the
      etiopathogenetic mechanisms responsible for the cyst development, the action of
      multiple coexisting factors seems to be the most applicable.

PMID- 16575298
TI  - Very late frontal relapse of medulloblastoma mimicking a meningioma in an adult:
      usefulness of 1H magnetic resonance spectroscopy and diffusion-perfusion magnetic
      resonance imaging for preoperative diagnosis: case report.
AB  - OBJECTIVE AND IMPORTANCE: We present a rare case of very long-term
      medulloblastoma relapse in an adult patient and discuss the pattern of recurrence
      and metabolic imaging of the tumor. CLINICAL PRESENTATION: A 45-year-old man was
      referred for evaluation of a frontobasal midline tumor 21 years after treatment
      of a cerebellar medulloblastoma by surgery followed by chemotherapy and
      craniospinal radiotherapy. Magnetic resonance images were suggestive of a
      meningioma. Several hypotheses were discussed, such as other radio-induced
      tumors, sarcomas, high-grade gliomas, or lymphomas (previous chemotherapy) and
      even recurrence of medulloblastoma. Preoperative exploration included H magnetic
      resonance single-voxel spectroscopy (35 and 135 ms echo time), diffusion imaging,
      and perfusion magnetic resonance imaging. INTERVENTION: On magnetic resonance
      spectroscopy, N-acetyl-aspartate and an elevated choline/creatine ratio were
      retrieved, with a huge unidentified peak at 1.27 parts per million (ppm).
      Myoinositol signal was present at both echo times. On diffusion imaging, the
      tumor appeared hyperintense, with a low apparent diffusion coefficient value of
      0.689. In the perfusion study, the maximal relative cerebral blood volume was 2.
      Metabolic imaging favored the diagnosis of medulloblastoma over the initially
      suspected diagnosis of meningioma. The patient underwent complete removal of the
      tumor that was confirmed to be a metastasis of his primary medulloblastoma. The
      postoperative course was uneventful, and complementary courses of radiotherapy
      and chemotherapy were planned. CONCLUSION: Late relapse should be considered,
      even after several decades, on occurrence of a second intracranial tumor in this
      context. Our observation validates the clinical interest of preoperative
      metabolic imaging for brain tumors with distinctive pattern.

PMID- 16575299
TI  - Trochlear nerve schwannoma with intratumoral hemorrhage: case report.
AB  - OBJECTIVE AND IMPORTANCE: Schwannomas originating from the trochlear nerve
      without neurofibromatosis are extremely rare. Thirty-four cases have previously
      been reported in the literature, and only 25 cases were pathologically diagnosed.
      In addition, intratumoral hemorrhage in intracranial schwannomas is also rare.
      Approximately 30 cases of intracranial schwannomas with intratumoral hemorrhage
      have been reported. CLINICAL PRESENTATION: A 42-year-old man presented with left
      hemiparesis and right trochlear nerve palsy. Magnetic resonance imaging revealed
      an abnormal cystic lesion beside the brainstem. His symptoms rapidly worsened
      after enlargement of the mass because of intratumoral hemorrhage. INTERVENTION:
      Gross total removal of the tumor was performed via the anterior transpetrosal
      approach. The tip of the trochlear nerve was fanned out and unified with the
      tumor. The tumor was diagnosed as a schwannoma. CONCLUSION: The patient's
      hemiparesis improved postoperatively, and he was discharged 1 week after the
      operation. Magnetic resonance imaging performed 4 months later revealed no
      regrowth of the tumor. Only right trochlear nerve palsy has persisted. This
      report is the second case of intratumoral hemorrhage from a trochlear nerve
      schwannoma.

PMID- 16575300
TI  - Significant improvement of visual functions after removal of an intracranial
      giant optic nerve glioma revealing exophytic growth: case report.
AB  - OBJECTIVE AND IMPORTANCE: Intracranial giant optic nerve gliomas, usually
      presumed as optic chiasmatic gliomas, are much less common. The architectural
      tumor form of optic nerve glioma without neurofibromatosis type 1 is usually the
      expansile-intraneural pattern. The exophytic optic nerve gliomas without
      neurofibromatosis type 1 are relatively uncommon. Surgical decompression for
      intracranial optic gliomas frequently leads to clinical improvement, but obvious
      improvement of vision is rare. We report a case that demonstrated significant
      recovery of visual function after removal of the intracranial giant optic nerve
      glioma, revealing exophytic growth. CLINICAL PRESENTATION: A 13-year-old boy
      presented with visual impairment in both eyes. Magnetic resonance images (MRI)
      disclosed a 6 cm diameter mass in the suprasellar area. On heavily T2-reversed
      MRIs, it was obvious that the intracranial portion of right optic nerve was
      enlarged, and optic tracts were shifted to the left by the tumor. The
      relationship of the tumor to the chiasma could not be affirmed on MRIs.
      INTERVENTION: A right frontotemporal craniotomy for decompression of the optic
      apparatus was performed. After the majority of the tumor was resected, it became
      clear that the tumor originated in the right optic nerve. The tumor exophytically
      grew and dislocated the optic chiasma and optic tracts. Significant improvement
      of visual functions began from the first week after surgery and continued
      gradually thereafter. The histological diagnosis was pilocytic astrocytoma. A
      follow-up MRI taken 4 years after surgery showed no regrowth of the residual
      tumor. CONCLUSION: Giant exophytic gliomas without neurofibromatosis type 1 may
      arise from the intracranial portion of an isolated optic nerve. Direct
      visualization of optic component by heavily T2-reversed MRI could more precisely
      delineate the relationship of the intracranial optic nerve glioma to the optic
      apparatus. Surgery may be indicated in giant exophytic intracranial optic nerve
      gliomas and preoperative postulated optic chiasmatic gliomas. Microsurgical
      resection can induce postoperative visual improvement without regrowth of the
      residual tumor.

PMID- 16575301
TI  - Perfusion and diffusion tensor imaging in a patient with locked-in syndrome after
      neurosurgical vascular bypass and endovascular embolization of a basilar artery
      aneurysm: case report.
AB  - OBJECTIVE AND IMPORTANCE: Locked-in syndrome is a state of preserved
      consciousness in the setting of quadriplegia, anarthria, and usually also
      includes lateral gaze palsy. It is most commonly associated with upper brainstem
      infarction variably sparing the third cranial nerve nucleus. There are likely
      many etiologies that contribute to this clinical syndrome. These are incompletely
      understood, and the syndrome remains a rare but devastating complication that can
      occur after neurosurgical and neurovascular interventions. Advanced magnetic
      resonance imaging techniques such as perfusion and diffusion tensor imaging may
      help to elucidate the mechanism behind locked-in syndrome. To the authors'
      knowledge, there are no reports in the literature of perfusion and diffusion
      tensor findings in patients with this syndrome. A postprocedural case of locked
      in syndrome is described with abnormalities on perfusion and diffusion tensor
      imaging in the absence of any changes in conventional magnetic resonance imaging.
      CLINICAL PRESENTATION: A 57-year-old man who presented with acute onset headache,
      ataxia, and other nonspecific symptoms was found on imaging to have a giant
      fusiform basilar artery aneurysm. INTERVENTION: A saphenous vein graft bypass
      between the proximal right external carotid artery and P2 segment of the right
      posterior cerebral artery followed immediately by endovascular embolization of
      the aneurysm sac and distal left vertebral artery was performed. CONCLUSION:
      Postprocedural angiography demonstrated patency of the bypass graft, and
      diffusion weighted imaging showed no evidence for acute brainstem infarction.
      Nevertheless, despite technically successful procedures and the absence of
      abnormalities on conventional magnetic resonance imaging, the patient developed
      quadriplegia and anarthria and remained in a locked-in state until he expired.
      Abnormalities were, however, seen on both perfusion and diffusion tensor imaging,
      where hypoperfusion, increased mean diffusivity, and decreased fractional
      anisotropy were observed in the ventral brainstem. The findings suggested a
      disruption of pontine white matter tracts. Advanced imaging techniques may allow
      us to image important microstructural changes that were previously not
      discernable and assist in the evaluation of patients with complex neurological
      sequelae such as locked-in syndrome.

PMID- 16575302
TI  - Normal pressure hydrocephalus in a patient with myotonic dystrophy: case report
      with a 10-year follow-up.
AB  - OBJECTIVE AND IMPORTANCE: Myotonic dystrophy (MD) is the most common adult
      muscular dystrophy involving multiple organs. Normal pressure hydrocephalus (NPH)
      is characterized by gait apraxia, urinary incontinence, and dementia. NPH in
      association with MD has been reported in only three cases. This report provides
      for the first time the complete evaluation, treatment, and long-term follow-up of
      a patient with NPH and MD. CLINICAL PRESENTATION: A 61-year-old man known to have
      MD complained of 4 years of progressive deterioration of long-term memory and
      gait disturbance, which was the main clinical feature. Computed tomography scan
      and magnetic resonance imaging showed ventricular enlargement. Intracranial
      pressure monitoring showed B waves with amplitude superior to 9 mm Hg in more
      than 5% of the recording. TECHNIQUE: We performed a ventriculoperitoneal shunt
      with clear postoperative improvement, confirming the diagnosis of NPH. The
      clinical improvement has remained stable through prolonged follow-up. CONCLUSION:
      Association between MD and NPH could be more than coincidental, and it is
      important to recognize this potential insidious association because a
      ventriculoperitoneal shunt can provide excellent long-term clinical improvement.

PMID- 16575303
TI  - Vertically unstable type III odontoid fractures: case report.
AB  - OBJECTIVE AND IMPORTANCE: Type III odontoid fractures are generally thought of as
      unstable fractures that can be successfully treated with an external orthosis.
      However, there is a rare subtype of Type III odontoid fractures that is similar
      in the degree of instability to atlanto-occipital dislocation injuries. Not
      recognizing or not treating this injury urgently and aggressively could lead to
      devastating iatrogenic neurological injuries such as quadriplegia and fatal lower
      brainstem palsies. CLINICAL PRESENTATION: We present the case of a 73-year-old
      woman with a vertically distracted Type III odontoid fracture and associated
      quadriparesis and brainstem deficits. The patient was kept in a rigid collar,
      placed in a kinematic bed, and admitted to the trauma service for the management
      of her life-threatening systemic injuries. Traction was not applied.
      INTERVENTION: As soon as the patient was systemically stable, she was taken to
      the operating room for C1-C2 fixation with a screw-rod construct supplemented by
      cable and structural iliac crest bone graft. CONCLUSION: Delayed recognition of
      this subtype of Type III odontoid fracture could have fatal or highly morbid
      consequences, such as quadriparesis/-plegia, lower brainstem dysfunction, and
      ventilator-dependence, for the patient. It is important to keep a high level of
      suspicion for this unusual subtype of Type III odontoid fracture.

PMID- 16575305
TI  - Cerebral perfusion pressure between 50 and 60 mmHg may be beneficial in head
      injured patients: a computerized secondary insult monitoring study.

PMID- 16575307
TI  - Clinical features and long-term results of spontaneous intracranial hypotension.

PMID- 16575309
TI  - Intracisternal sodium nitroprusside fails to prevent vasospasm in nonhuman
      primates.

PMID- 16575311
TI  - Pituitary carcinoma: a clinicopathological review.

PMID- 16575313
TI  - Patient reports of satisfaction after microvascular decompression and partial
      sensory rhizotomy for trigeminal neuralgia.

PMID- 16575317
TI  - Microvascular decompression for trigeminal neuralgia in the elderly: a review of
      the safety and efficacy.

PMID- 16575319
TI  - Application of nicardipine prolonged-release implants: analysis of 97 consecutive
      patients with acute subarachnoid hemorrhage.

PMID- 16575322
TI  - Natural history of intracranial atherosclerosis: a critical review.
AB  - Intracranial atherosclerosis is responsible for a significant number of strokes.
      Medical therapy for this condition may fail, leaving patients at high risk for
      cerebral infarction and death. With advances in endovascular techniques on the
      horizon, understanding the prognosis of conservative treatment is essential for
      appropriate patient management. Although several small studies have attempted to
      address this issue, a comprehensive review regarding the natural history of
      intracranial atherosclerosis in a vessel-specific manner is lacking. Owing to
      heterogeneity in vascular anatomy and physiology, atherosclerosis in different
      vessels may represent diseases with fundamentally distinct courses. Therefore, it
      is important to distinguish vascular territories when studying the natural
      history of this condition. To this end, we critically review the literature
      investigating medical management of patients with intracranial atherosclerosis,
      segregating our findings by vessel. Analysis by this method suggests that middle
      cerebral artery atherosclerosis carries a lower mortality rate than stenoses
      involving other intracranial vessels, and that asymptomatic disease follows a
      more benign course. In addition, plaque progression and transcranial Doppler
      detected microemboli seem to predict outcome according to limited data. This
      comprehensive review may help guide clinical decision-making and therapeutic
      developments in this patient population.

PMID- 16575323
TI  - Complications of cerebral arteriovenous malformation embolization: multivariate
      analysis of predictive factors.
AB  - OBJECTIVE: Embolization is an important therapeutic modality in the
      multidisciplinary management of arteriovenous malformations (AVM); however, prior
      series have reported a wide variability in overall complication rates caused by
      embolization (10-50% neurological deficit, 1-4% mortality). In this study, we
      reviewed our experience with AVM embolization and analyzed factors that might
      predict complications and clinical outcomes after AVM embolization. METHODS: We
      analyzed our combined neurovascular unit's results with AVM embolization from
      1993 to 2004 for the following outcomes measures: 1) clinically significant
      complications, 2) technical complications without clinical sequelae, 3) discharge
      Glasgow Outcome Scale score, and 4) death. To determine embolization efficacy, we
      analyzed perioperative blood transfusion and rate of AVM obliteration. Univariate
      and multivariate analyses were performed for patient age, sex, history of
      rupture, history of seizure, associated aneurysms, AVM size, deep venous
      drainage, eloquent location, Spetzler-Martin grade, number of embolization
      stages, number of pedicles embolized, and primary treatment modality. RESULTS:
      Over an 11 year period, 295 embolization procedures (761 pedicles embolized) were
      performed in 168 patients with embolization as the primary treatment modality (n
      = 16) or as an adjunct to surgery (n = 124) or radiosurgery (n = 28). There were
      a total of 27 complications in this series, of which 11 were clinically
      significant (6.5% of patients, 3.7% per procedure), and 16 were technical
      complications (9.5% of patients, 5.4% per procedure). Excellent or good outcomes
      (Glasgow Outcome Scale > or = 4) were observed in 152 (90.5%) patients.
      Unfavorable outcomes (Glasgow Outcome Scale 1-3) as a direct result of
      embolization were both 3.0% at discharge and at follow-up, with a 1.2%
      embolization-related mortality. In the 124 surgical patients, 96.8% had complete
      AVM obliteration after initial resection, and 31% received perioperative
      transfusion (mean 1.4 units packed red blood cells per surgical patient).
      Predictors of unfavorable outcome caused by embolization by univariate analysis
      were deep venous drainage (P < 0.05), Spetzler-Martin Grade III to V (P < 0.05),
      and periprocedural hemorrhage (P < 0.0001) and by multivariate analysis were
      Spetzler-Martin III to V (odds ratio 10.6, P = 0.03) and periprocedural
      hemorrhage (odds ratio 17, P = 0.004). CONCLUSION: In a single-center,
      retrospective, nonrandomized study, 90.5% of patients had excellent or good
      outcomes after AVM embolization, with a complication rate lower than previously
      reported. Spetzler-Martin grade III to V and periprocedural hemorrhage were the
      most important predictive factors in determining outcome after embolization.

PMID- 16575324
TI  - Endovascular treatment of unruptured intracranial aneurysms: occurrence of
      thromboembolic events.
AB  - OBJECTIVE: The purpose of this study was to evaluate the frequency and causes of
      thromboembolic events associated with endovascular embolization of asymptomatic
      aneurysms. Correlations between radiological findings (aneurysm size,
      localization, embolization time, number of coils used, as well as patient age)
      were evaluated with the occurrence of thromboembolic events and clinical
      findings. METHODS: Sixty-eight patients treated for unruptured intracranial
      aneurysms (mean age, 49 yr) were evaluated. Hyperintense lesions on diffusion
      weighted imaging were analyzed in 50 patients. Aneurysm size was 3 to 15 mm.
      RESULTS: Complete occlusion of the aneurysms was achieved in 55 of 68 (82%). One
      patient had a transient paresis. There was one infarction and one aneurysm
      rupture during the procedure with no consecutive neurological symptoms. We found
      new hyperintense lesions in 21 of 50 (42%) diffusion weighted imaging studies. In
      43% of these, there was only one lesion smaller than 2 mm. In 33%, there was more
      than one lesion less than 2 mm; in 19%, we found a lesion of 2 to 10 mm in size.
      In one case, a lesion greater than 10 mm occurred. There was no correlation
      between aneurysm location and the occurrence of lesions or among the number of
      coils used, the size of the aneurysm, patient age, or embolization time.
      Mortality rate was 0%, morbidity 4.0%. If the 18 aneurysms where no diffusion
      weighted imaging was obtained are included, morbidity is 2.9%. CONCLUSION: The
      high rate of thromboembolic events suggests that heparin is not sufficient to
      prevent ischemic lesions. An antiplatelet therapy, started before or during
      intervention, might diminish thrombus formation.

PMID- 16575326
TI  - Medial sphenoid wing meningiomas: clinical outcome and recurrence rate.
AB  - OBJECTIVE: To provide clinical data concerning the visual outcome and recurrence
      rate of medial sphenoid wing meningiomas in consideration of two different
      subgroups of this tumor entity. METHODS: Among 256 sphenoid wing meningiomas,
      there were 108 medial sphenoid wing meningiomas of globoid shape. They were
      classified into Group 1 (without cavernous sinus involvement) and Group 2 (with
      cavernous sinus involvement). En plaque meningiomas were excluded from the
      analysis. The charts of the patients including surgical records, discharge
      letters, follow-up records, and imaging studies were analyzed retrospectively.
      RESULTS: There were 39 Group 1 tumors and 69 Group 2 tumors. For microsurgical
      tumor removal, the frontolateral (15.7%) or the pterional approach (84.3%) was
      performed. Total resection was achieved in 92.3% of patients with Group 1 tumors
      and 14.5% of those with Group 2 tumors. Radiological recurrence was observed in
      7.7% (Group 1 tumors) and 27.5% (Group 2 tumors). The mean follow-up time was
      79.04 months (6.59 yr). Improvement of visual function (or stable visual
      function) was observed in 56% (44%) of patients with Group 1 tumors, in 30% (60%)
      with newly diagnosed Group 2 tumors, and 10% (70%) undergoing recurrent surgery
      for Group 2 tumors. CONCLUSION: Group 1 meningiomas present a more favorable
      subgroup with fortunate visual outcome. In Group 2 tumors, visual improvement was
      less favorable and radical removal is limited because of cavernous sinus
      infiltration, with consequential higher recurrence rates. Patients harboring
      recurrent Group 2 tumors with deteriorating visual function profit from
      microsurgery because vision can be preserved on the same preoperative level in
      the majority.

PMID- 16575325
TI  - Endovascular surgery for proximal posterior inferior cerebellar artery aneurysms:
      an analysis of Glasgow Outcome Score by Hunt-Hess grades.
AB  - OBJECTIVE: Proximal posterior inferior cerebellar artery (PICA) aneurysms
      represent a subset of posterior circulation aneurysms that can be routinely
      treated with either clipping or coiling. The literature contains limited numbers
      of patients with proximal PICA aneurysms treated with endovascular surgery. We
      report our experience with endovascular surgery of proximal PICA aneurysms with
      emphasis on patients with poor Hunt-Hess grades. METHODS: We reviewed 31
      consecutive patients with proximal PICA aneurysms who were treated with
      endovascular surgery. The following data were analyzed: age, sex, size of
      aneurysm, Hunt-Hess grade at presentation, Fisher grade at presentation,
      angiographic result after embolization, complications, number of days
      hospitalized, duration of follow-up, angiographic follow-up results, and Glasgow
      Outcome Score at follow-up. RESULTS: Excellent angiographic occlusion was
      achieved in 30 of 31 (97%) patients. Clinical follow-up with Glasgow Outcome
      Score was performed on every patient an average of 10 months later. Twenty-one of
      31 (68%) patients had good outcomes (Glasgow Outcome Score I or II) at follow-up.
      Of the patients who presented with a favorable clinical grade (Hunt-Hess 0-III),
      13 of 15 (87%) had good outcomes at follow-up. Of the patients who presented with
      a poor clinical grade (Hunt-Hess Grade IV or higher), 8 of 16 (50%) had good
      outcomes at follow-up. CONCLUSION: This series demonstrates the safety and
      efficacy of endovascular surgery for proximal PICA aneurysms. Many patients with
      poor Hunt-Hess grades from ruptured PICA aneurysms ultimately had a good outcome.
      This could be secondary to early, aggressive treatment of hydrocephalus and the
      minimally invasive nature of the endovascular approach.

PMID- 16575327
TI  - Dexamethasone and enhancing solitary cerebral mass lesions: alterations in
      perfusion and blood-tumor barrier kinetics shown by magnetic resonance imaging.
AB  - OBJECTIVE: Glucocorticoid analogues are often administered to patients with
      intracranial space-occupying lesions. Clinical response can be dramatic, but the
      neurophysiological response is not well documented. This study sought to
      investigate the blood-lesion barrier, blood-brain barrier, and cerebral perfusion
      characteristics of patients who have undergone such therapy using magnetic
      resonance imaging. METHODS: Seventeen patients with intracranial mass-enhancing
      lesions underwent magnetic resonance imaging before and after 3 days of high-dose
      dexamethasone therapy. Assessments of blood-lesion barrier and blood-brain
      barrier integrity were based on a dynamic T1-weighted exogenous contrast
      technique that yielded the normalized maximal change in contrast uptake (T1
      uptake). Perfusion was assessed using a dynamic T2*-weighted exogenous contrast
      technique to yield relative regional cerebral blood volume and first-moment mean
      transit time. Comparisons were made in T1-uptake, regional cerebral blood volume,
      and first-moment mean transit time of both enhancing lesion and contralateral
      normal-appearing white matter (CNAWM) obtained before and after dexamethasone.
      RESULTS: Significant reduction in T1-uptake was observed (19% decrease, P <
      0.005) within enhancing pathological tissue, whereas no significant alteration
      was detected in CNAWM. Regional cerebral blood volume was significantly reduced
      in both enhancing tissue (28% decrease, P < 0.005) and in CNAWM (20% decrease, P
      < 0.001). Bolus first-moment mean transit time significantly increased (2.0 s
      prolongation, P < 0.05) in CNAWM, whereas there was no significant change (1.4 s
      prolongation, P > 0.05) within enhancing tissue. CONCLUSION: Glucocorticoid
      analogue therapy not only affects the permeability of the blood-lesion barrier
      and lesion blood volume but also affects blood flow within normal-appearing
      contralateral parenchyma. There is a need for controls in steroid therapy in
      magnetic resonance imaging studies, which involve assessments of cerebrovascular
      function.

PMID- 16575328
TI  - Acute traumatic intraparenchymal hemorrhage: risk factors for progression in the
      early post-injury period.
AB  - OBJECTIVE: To characterize the natural course of traumatic intraparenchymal
      contusions and hematomas (IPHs) and to identify risk factors for IPH progression
      in the acute post-injury period. METHODS: A retrospective analysis was performed
      on a prospective observational database containing 113 head trauma patients
      exhibiting 229 initially nonoperated acute IPHs. The main outcome variable was
      radiographic evidence of IPH progression on serially obtained head computed
      tomographic (CT) scans. Secondary outcomes included the actual amount of IPH
      growth and later surgical evacuation. Univariate and multivariate analyses (using
      a generalized estimate equation) were applied to both demographic and initial
      radiographic features to identify risk factors for IPH progression and surgery.
      RESULTS: Overall, 10 IPHs (4%) shrank, 133 (58%) remained unchanged, and 86 (38%)
      grew between the first and second head CT scan. IPH progression was independently
      associated with the presence of subarachnoid hemorrhage (odds ratio [OR], 1.6;
      95% confidence interval [CI], 1.12-2.3), presence of a subdural hematoma (OR,
      1.94; 95% CI, 1.1-3.43), and initial size (OR, 1.11; 95% CI, 1.02-1.21, for each
      cm volume). Size of initial IPH proportionately correlated with the amount of
      subsequent growth (linear regression, P < 0.001). Worsened Glasgow Coma Score
      between initial and follow-up head CT scan (OR, 8.6; 95% CI, 1.5-50), IPH growth
      greater than 5 cm (OR, 7.3; 95% CI, 1.6-34), and effacement of basal cisterns on
      initial CT scan (OR, 9.0; 95% CI, 1.5-52) were strongly associated with late
      surgical evacuation. CONCLUSION: A large proportion of IPHs progress in the acute
      post-injury period. IPHs associated with subarachnoid hemorrhage, a subdural
      hematoma, or large initial size should be monitored carefully for progression
      with repeat head CT imaging. Effacement of cisterns on the initial head CT scan
      was strongly predictive of failure of nonoperative management, thereby leading to
      surgical evacuation. These findings should be important factors in the
      understanding and management of IPH.

PMID- 16575329
TI  - Conservative management of patients with cerebrospinal fluid shunt infections.
AB  - OBJECTIVE: In patients with cerebrospinal fluid (CSF) shunt infection, removal of
      the shunt and antibiotic administration is the current standard of care. In 1986,
      we developed a protocol for the conservative management of patients with infected
      but functioning shunts. Treatment was based on the administration of a
      combination of intraventricular and systemic antibiotics. Intraventricular
      antibiotics were instilled via a separate access device. The purpose of this
      report is to describe our experience with this therapeutic intervention. METHODS:
      An observational study of all patients treated for CSF shunt infection between
      1986 and 2003 was undertaken. Cure was defined by sterile CSF after completion of
      therapy and sterile shunt components at next revision or long-term freedom from
      recurrent infection (follow-up period, 6-88 mo). RESULTS: In total, 43 of 122
      patients with CSF shunt infections were treated conservatively according to our
      protocol. Overall, 84% of these patients were cured, with a 92% success rate for
      patients with infections caused by bacteria other than Staphylococcus aureus.
      This included 30 coagulase-negative staphylococcal infections, of which two were
      treatment failures. We abandoned conservative treatment of patients with
      Staphylococcus aureus infections after early experience demonstrated that the
      success rate (four treatment failures in seven patients) was markedly lower than
      that for other pathogens. During the treatment and follow-up periods, there were
      three deaths, two of which were unrelated to shunt infection; treatment failure
      could not be completely excluded in the remaining patient. There was no toxicity
      related to intraventricular antibiotic administration. The incidence of shunt
      blockage among patients who were treated conservatively was not significantly
      different from that among a large cohort of patients with uninfected shunts. Ten
      patients received part of their courses of treatment as outpatients. CONCLUSION:
      The success rate of conservative management of patients with CSF shunt infections
      caused by coagulase-negative staphylococci is comparable with those in the
      published literature for patients treated conventionally. This form of management
      avoids surgical intervention, with its attendant risks, and is safe.

PMID- 16575330
TI  - High-resolution three-dimensional magnetic resonance angiography and three
      dimensional spoiled gradient-recalled imaging in the evaluation of neurovascular
      compression in patients with trigeminal neuralgia: a double-blind pilot study.
AB  - OBJECTIVE: To assess the value of high-resolution three-dimensional (3D) time-of
      flight (TOF) magnetic resonance (MR) angiography and gadolinium (Gad)-enhanced 3D
      spoiled gradient-recalled imaging in the visualization of neurovascular
      compression in patients with trigeminal neuralgia. METHODS: Forty-eight patients
      with unilateral trigeminal neuralgia underwent high-resolution 3D TOF MR
      angiography. After administration of a contrast agent, a 3D spoiled gradient
      recalled sequence (3D Gad) was run. Images were reviewed by a radiologist blinded
      to clinical details. All patients underwent microvascular decompression surgery.
      Microdissection of the trigeminal nerve and compressing vessels was videotaped
      during surgery and reviewed by surgeons uninvolved in patient care. Results from
      neuroradiological studies were then compared with findings on operative
      videotapes. RESULTS: MR angiography in combination with 3D Gad imaging identified
      surgically verified neurovascular contact in 42 of 46 (91%) symptomatic nerves.
      The offending vessel (artery, vein) was correctly identified in 31 of 41 cases
      (sensitivity, 76%; specificity, 75%). Neurovascular compression was observed in
      71% of asymptomatic nerves with a trend toward greater compression severity on
      the symptomatic nerve (P < 0.09). Agreement between the direction of
      neurovascular contact defined by 3D TOF MR angiography and 3D Gad and findings at
      surgery was good (kappa = 0.78; 95% confidence interval, 0.61-0.94). CONCLUSION:
      Double-blind assessment of surgical and neuroradiological findings confirms that
      neurovascular compression can be visualized with good sensitivity in patients
      with trigeminal neuralgia by 3D TOF MR angiography in combination with Gad
      enhanced 3D spoiled gradient-recalled sequences. Anatomic relationships defined
      by this method can be useful in predicting surgical findings.

PMID- 16575331
TI  - CyberKnife radiosurgery for benign intradural extramedullary spinal tumors.
AB  - OBJECTIVE: Microsurgical resection of benign intradural extramedullary spinal
      tumors is generally safe and successful, but patients with neurofibromatosis,
      recurrent tumors, multiple lesions, or medical problems that place them at higher
      surgical risk may benefit from alternatives to surgery. In this prospective
      study, we analyzed our preliminary experience with image-guided radiosurgical
      ablation of selected benign spinal neoplasms. METHODS: Since 1999, CyberKnife
      (Accuray, Inc., Sunnyvale, CA) radiosurgery was used to manage 51 patients
      (median age, 46 yr; range, 12-86 yr) with 55 benign spinal tumors (30
      schwannomas, nine neurofibromas, 16 meningiomas) at Stanford University Medical
      Center. Total treatment doses ranged from 1600 to 3000 cGy delivered in
      consecutive daily sessions (1-5) to tumor volumes that varied from 0.136 to 24.6
      cm. RESULTS: Less than 1 year postradiosurgery, three of the 51 patients in this
      series (one meningioma, one schwannoma, and one neurofibroma) required surgical
      resection of their tumor because of persistent or worsening symptoms; only one of
      these lesions was larger radiographically. However, 28 of the 51 patients now
      have greater than 24 months clinical and radiographic follow-up. After a mean
      follow-up of 36 months, all of these later lesions were either stable (61%) or
      smaller (39%). Two patients died from unrelated causes. Radiation-induced
      myelopathy appeared 8 months postradiosurgery in one patient. CONCLUSION:
      Although more patients studied over an even longer follow-up period are needed to
      determine the long-term efficacy of spinal radiosurgery for benign extra-axial
      neoplasms, short-term clinical benefits were observed in this prospective
      analysis. The present study demonstrates that CyberKnife radiosurgical ablation
      of such tumors is technically feasible and associated with low morbidity.

PMID- 16575332
TI  - The role of non-invasive computed tomography in patients with suspected dural
      fistulas with spinal drainage.
AB  - OBJECTIVE: Accurate diagnosis and demonstration of the angioarchitecture and
      localization of a spinal dural arteriovenous fistula is of crucial importance
      before treatment. Selective spinal angiography (DSA) has been considered the
      standard technique, but is invasive, time-consuming, and may be falsely negative.
      This report evaluates the use of noninvasive vascular imaging (computed
      tomographic and magnetic resonance angiography [MRA]) in patients suspected to
      have a dural fistula with spinal drainage. METHOD: Ten consecutive patients had
      DSA and multidetector computed tomographic angiography (MDCTA), eight also had
      MRA. Nine were men with an average age of 67 years. In nine patients, the
      diagnosis was confirmed at surgery or intravascular treatment. Eight were proven
      to have a spinal dural fistula. In two, the fistula was within the cervical
      cranial dura. In all patients, the venous drainage involved only the spinal
      venous plexus. RESULTS: MDCTA identified the level of the feeding artery in nine
      patients. In two cases, selective DSA failed to show the abnormality found on
      MDCTA, but both were confirmed at surgery. MRA was diagnostic in a case in which
      the lesion was not accurately depicted by either MDCTA or DSA. MRA was less
      accurate than MDCTA in determining the level of the feeding artery. CONCLUSION:
      MDCTA and MRA can direct and focus DSA. MDCTA gives additional useful three
      dimensional bone detail and localization information for the surgeon. It may
      replace DSA if surgery is the planned treatment.

PMID- 16575333
TI  - Efficacy of postural reduction in osteoporotic vertebral compression fractures
      followed by percutaneous vertebroplasty.
AB  - OBJECTIVE: Vertebroplasty in the symptomatic osteoporotic vertebral fracture has
      become increasingly popular. However, there have been some limitations in
      restoring the height of the collapsed vertebrae and in preventing the leaking of
      cement. In the severely collapsed vertebrae of more than two thirds of their
      original height, vertebroplasty is regarded as a contraindication. We tried
      postural reduction using a soft pillow under the compressed level. This study was
      undertaken to investigate the effectiveness of the combination of postural
      reduction and vertebroplasty for re-expansion and stabilization of the
      osteoporotic vertebral fractures. METHODS: A total of 75 patients with single
      level vertebral compression fracture were treated with postural reduction
      followed by vertebroplasty. In 30 patients, the vertebral body was severely
      collapsed more than two-thirds of its original height. We calculated the
      compression ratio (anterior height/posterior height) and measured the Cobb angle.
      We analyzed the degree of re-expansion according to the onset duration. RESULTS:
      The mean compression ratio was 0.60 +/- 0.15 initially and increased to 0.75 +/-
      0.17 after vertebroplasty. The mean Cobb angle was 16.14 +/- 11.29 degrees and
      corrected to 10.71 +/- 12.08 degrees. The degree of re-expansion showed
      significant relation with the onset duration. Twenty-eight of 30 (93%) severely
      collapsed vertebrae re-expanded after postural reduction, which made
      vertebroplasty possible. CONCLUSION: This new method of vertebroplasty leads to
      significant restoration of height and correction of kyphosis. The re-expansion
      was closely related with onset duration. In cases of severely collapsed vertebrae
      which is able to be re-expanded by postural reduction, vertebroplasty could be
      applied safely.

PMID- 16575334
TI  - GliaSite brachytherapy for treatment of recurrent malignant gliomas: a
      retrospective multi-institutional analysis.
AB  - OBJECTIVE: To review the cumulative experience of 10 institutions in treating
      recurrent malignant gliomas with the brachytherapy device, GliaSite Radiation
      Therapy System. METHODS: The patient population consisted of 95 patients with
      recurrent grade 3 or 4 gliomas, a median age of 51 years, and a median Karnofsky
      performance status score of 80. All patients had previously undergone resection
      and had received external beam radiotherapy as part of their initial treatment.
      After recurrence, each patient underwent maximal surgical debulking of their
      recurrent lesion and placement of an expandable balloon catheter (GliaSite) in
      the tumor cavity. The balloon was afterloaded with liquid I (Iotrex) to deliver a
      median dose of 60 Gy to an average depth of 1 cm with a median dose rate of 52.3
      Gy/hr. Patients were carefully followed with serial magnetic resonance imaging
      and monthly examinations for tumor progression, side effects, and survival.
      RESULTS: The median survival for all patients, measured from date of GliaSite
      placement, was 36.3 weeks with an estimated 1 year survival of 31.1%. The median
      survival was 35.9 weeks for patients with an initial diagnosis of glioblastoma
      multiforme and 43.6 weeks for those with non- glioblastoma multiforme malignant
      gliomas. Analysis of the influence of various individual prognostic factors on
      patient survival demonstrated that only Karnofsky performance status
      significantly predicted for improved survival. There were three cases of
      pathologically documented radiation necrosis. CONCLUSION: Reirradiation of
      malignant gliomas with the GliaSite Radiation Therapy System after reresection
      seems to provide a modest survival benefit above what would be expected from
      surgery alone. This report not only confirms the initial results of the
      feasibility study but provides evidence that similar outcomes can be obtained
      outside of a clinical trial.

PMID- 16575335
TI  - A novel platform for image-guided ultrasound.
AB  - OBJECTIVE: The combination of classic neuronavigation and intraoperative
      ultrasound is a recent innovation in image guidance technology. However, this
      technique requires two hardware components (neuronavigation and an ultrasound
      system). It was the aim of the study to describe a new simplified technology of a
      so-called one-platform navigation system developed by our institution in
      collaboration with the industry and to demonstrate its range of various
      applications. METHODS: An ultrasound device (IGSonic; BrainLAB, Munich, Germany)
      is integrated into the VectorVision2 navigation system (BrainLAB, Munich,
      Germany). The IGSonic Probe 10V5 is connected to the VectorVision Navigation
      station via an IGSonic Device Box. Once the ultrasound probe is calibrated, the
      navigated ultrasound displays the sonographic image of the intracranial anatomy
      on the navigation screen in a composed overlay fashion. It might depict vascular
      structures within the ultrasound plane by a duplex mode. Ultrasound can also be
      operated independently from navigation. RESULTS: The VectorVision2 system
      combines intraoperative ultrasound data sets with preoperatively acquired
      neuronavigation data sets in plug and play fashion. The system provides a cost
      effective intraoperative imaging modality that offers a good anatomic orientation
      by various composite images, including the display of the amount of brain shift.
      In our institution, the comprehensible interface led to a routine use of the
      technology by several neurosurgeons who had not been familiar with the ultrasound
      technology before. CONCLUSION: The integration of an ultrasound device into an
      existing navigation system has been successfully developed. The system offers a
      friendly user interface and cost-effective intraoperative imaging feedback.
      Although brain shift can be visualized by an image overlay technology as
      demonstrated by the present system, future developments should aim at fusion
      techniques of both intra- and preoperative image data sets.

PMID- 16575336
TI  - Is routine intraoperative angiography in the surgical treatment of cerebral
      aneurysms justified? A consecutive series of 147 aneurysms.
AB  - OBJECTIVE: The role of intraoperative angiography (IA) in the surgical treatment
      of cerebral aneurysms has remained extremely controversial. We determine the
      frequency and predictors of unanticipated findings necessitating clip adjustment
      established on postoperative angiography (PA) in a consecutive series of 147
      aneurysms. On the basis of published series, we discuss the utility, safety,
      accuracy, and cost effectiveness of adjunct IA in the surgical treatment of
      cerebral aneurysms. METHODS: We retrospectively examined the charts of 124
      consecutive patients harboring 147 aneurysms that were surgically clipped between
      December 2000 and March 2005 and had PA available for review. Patient
      demographics, aneurysm size, location, Hunt and Hess score, Fisher grade, mode of
      aneurysm discovery, time between discovery and surgery, and PA results, as
      determined by a blinded independent neuroradiologist, were recorded. RESULTS: PA
      demonstrated two (1.4%) unexpected residuals, four anticipated residuals (2.7%),
      and four (2.7%) vessel compromises. Of the six unanticipated outcomes, two of two
      (100%) unexpected residuals and three of four (75%) vessel compromises were from
      large aneurysms (P = 0.0001 each). Middle cerebral artery aneurysms comprised 5
      of 10 (50%) imperfect outcomes (three expected remnants and two vessel
      occlusions), which trended toward significance (P = 0.06). CONCLUSION: IA is
      recommended during the surgical clipping of complex or large aneurysms and some
      middle cerebral artery aneurysms. High cost-benefit ratio, false-negative rate,
      and moderate risk, however, preclude routine use. With future technological
      advances, IA may warrant broader use by replacing postoperative studies in the
      neurosurgical management of intracranial aneurysms.

PMID- 16575337
TI  - Microsurgical anatomy of the cochlear nuclei.
AB  - OBJECTIVE: The dorsal and ventral cochlear nuclei are exposed when treating
      lesions involving the fourth ventricle and the cerebellopontine angle. Precisely
      locating the nuclei is important in the placement of the auditory brainstem
      implantation and in intraoperative monitoring of auditory evoked potentials. This
      study examined the microsurgical anatomy of the cochlear nuclei. METHODS: The
      relationships and the surgical approaches to the nuclei were examined in 20
      formalin-fixed specimens with the aid of an operating microscope. RESULTS: The
      dorsal cochlear nucleus is located in the floor of the lateral recess of the
      fourth ventricle on the posterior surface of the inferior cerebellar peduncle
      where it produces a prominence, the auditory tubercle. The ventral cochlear
      nucleus is positioned on the lateral surface of the inferior cerebellar peduncle
      where it often straddles the anterior edge of the foramen of Luschka at the
      junction of the lateral recess and cerebellopontine angle and produces less of a
      prominence on the surface of the brainstem than on the dorsal nucleus.
      CONCLUSION: Both the dorsal and ventral cochlear nuclei can be exposed after
      opening the foramen of Luschka and the lateral recess of the fourth ventricle by
      the retrosigmoid or translabyrinthine approach. The dorsal cochlear nucleus is
      positioned so that it would be damaged by a tumor within or approaches to the
      floor of the lateral recess. The ventral cochlear nucleus is positioned so that
      it would be vulnerable to damage by tumors within or operative approaches to the
      cerebellopontine angle. The dorsal cochlear nucleus and the adjacent
      intraventricular part of the ventral cochlear nucleus have anatomic
      characteristics that make them the preferable site of placement for the auditory
      brain stem implant.

PMID- 16575338
TI  - Proliferative activity through extracellular signal-regulated kinase of smooth
      muscle cells in vascular walls of cerebral arteriovenous malformations.
AB  - OBJECTIVE: We examined the expression and localization of phosphorylated
      extracellular signal-regulated kinase (pERK) and proliferation-related antigens
      in human cerebral arteriovenous malformations (AVMs) to clarify the role of
      vascular remodeling via this pathway in the development of the lesions. METHODS:
      Thirteen cerebral AVMs and five control specimens were analyzed using
      immunohistochemical methods. Specimens were obtained from the patients during the
      surgical procedures. Control middle cerebral artery samples were obtained during
      autopsies. RESULTS: We performed immunohistochemical analysis of AVMs by using an
      antibody specifically recognizing pERK. pERK immunoreactivity was detected in all
      specimens. Among the control specimens, only weak pERK immunoreactivity was
      detected, mainly in the intima. pERK immunoreactivity was located in nuclei of
      cells in the endothelial layer and media. Semiquantitative analysis for pERK
      immunoreactivity showed that the immunoreactivity score in the media was
      significantly higher for the AVM than for the control specimens. The results of
      double staining for pERK and proliferating cell nuclear antigen indicated that
      these immunoreactivities were colocalized in the same cells. Moreover, those
      cells in the media were immunoreactive for alpha-actin, indicating that they were
      smooth muscle cells. CONCLUSION: pERK was detected in smooth muscle cells of the
      vascular walls of AVMs. It may function in the proliferative activity of smooth
      muscle cells. Vascular remodeling through pERK may play an important role in the
      growth and maintenance of cerebral vascular malformations.

PMID- 16575339
TI  - Responses of arteriovenous malformations to radiosurgery: ultrastructural
      changes.
AB  - OBJECTIVE: To examine the ultrastructural changes in arteriovenous malformations
      (AVMs) after radiosurgery and to explore the possible mechanisms of posttreatment
      obliteration and hemorrhage. METHODS: Twenty-two specimens, among them three
      irradiated AVMs (size, 3-6 cm), 15 nonirradiated AVMs, and four normal controls
      were processed for ultrastructural study immediately after removal. Transmission
      electron microscopy was used to compare the vasculature of irradiated AVMs with
      nonirradiated AVMs and normal controls. RESULTS: Thirty-three months
      postradiosurgery, partial vaso-occlusion (36-74% lumen) occurred by coagulation
      of cytoplasmic debris and proteinaceous material leaking from the endothelium.
      Forty-eight months postradiosurgery, heterogeneous thrombus formation (86-96%
      lumen) with fibrinoid and proteinaceous materials was observed. Sixty-four months
      postradiosurgery, complete luminal closure (90-100% lumen) by a fibrin thrombus
      was seen in vessels with diameters up to 5.5 mm including feeding arteries and
      draining veins. In occluded vessels, there was extensive degeneration of
      endothelial cells, subendothelial fibroblasts, and myofibroblasts.
      Neoproliferation and endothelialization of smooth muscle cells with Weibel-Palade
      bodies was observed in arteries. CONCLUSION: Radiosurgery causes irreversible
      cellular damage of the vascular wall. Partial vaso-occlusion that increases blood
      flow in remaining vessels and degenerative changes on the blood-brain barrier may
      contribute to hemorrhage at early stage postradiosurgery. Radiosurgery stimulates
      neoproliferating and endothelializing smooth muscle cells in vessel walls, which
      might lead to narrowing of the vessel lumina. Complete vaso-occlusion achieved 64
      months postradiosurgery suggested a minimum follow-up duration of 5 years to
      determine final outcome of radiosurgery. Histological end point of vaso-occlusion
      of AVMs takes longer time than neuroimaging endpoint of complete obliteration.

PMID- 16575340
TI  - Multiphoton excitation of autofluorescence for microscopy of glioma tissue.
AB  - OBJECTIVE: Intraoperative detection of residual tumor tissue in glioma surgery
      remains an important challenge because the extent of tumor removal is related to
      the prognosis of the disease. Multiphoton excited fluorescence tomography of
      living tissues provides high-resolution structural and photochemical imaging at a
      subcellular level. In this conceptual study, we have used multiphoton microscopy
      and fluorescence lifetime imaging (4D microscopy) to image cultured glioma cell
      lines, solid tumor, and invasive tumor cells in an experimental mouse glioma
      model and human glioma biopsy specimens. MATERIAL AND METHODS: A laser imaging
      system containing a mode-locked 80 MHz titanium:sapphire laser with a tuning
      range of 710 to 920 nm, a scan unit, and a time correlated single photon counting
      board was used to generate autofluorescence intensity images and fluorescence
      lifetime images of cultured cell lines, experimental intracranial gliomas in
      mouse brain, and biopsies of human gliomas. RESULTS: Multiphoton microscopy of
      native tumor bearing brain provided structural images of the normal brain anatomy
      at a subcellular resolution. Solid tumor, the tumor-brain interface, and single
      invasive tumor cells could be visualized. Fluorescence lifetime imaging
      demonstrated significantly different decay of the fluorescent signal in tumor
      versus normal brain, allowing a clear definition of the tumor-brain interface
      based on this parameter. Distinct fluorescence lifetimes of endogenous
      fluorophores were found in different cellular compartments in cultured glioma
      cells. The analysis of the relationship between the laser excitation wavelength
      and the lifetime of excitable fluorophores demonstrated distinct profiles for
      cells of different histotypes. CONCLUSION: Multiphoton excited fluorescence of
      endogenous fluorophores allows structural imaging of tumor and central nervous
      system histo-architecture at a subcellular level. The analysis of the decay of
      the fluorescent signal within specific excitation volumes by fluorescent lifetime
      imaging discriminates glioma cells and normal brain, and the excitation/lifetime
      profiles may further allow differentiation of cellular histotypes. This
      technology provides a noninvasive optical tissue analysis that may potentially be
      applied to an intraoperative analysis of resection plains in tumor surgery.

PMID- 16575341
TI  - Nerve regeneration through nerve autografts and cold preserved allografts using
      tacrolimus (FK506) in a facial paralysis model: a topographical and
      neurophysiological study in monkeys.
AB  - OBJECTIVE: Nerve regeneration through cold preserved nerve allografts is
      demonstrated, and treatment of nerve allografts with FK506 induces better
      regeneration than other immunosuppressants. We study nerve regeneration through
      cold preserved nerve allografts temporarily treated with FK506 and compare it
      with the regeneration obtained using classic nerve autografts in a facial
      paralysis model in monkeys. METHODS: A trunk of the facial nerve on both sides
      was transected in eight monkeys and immediately repaired with a 3 to 4 cm nerve
      autograft or allograft. FK506 was administered to the animals of the allograft
      group for 2 months, and nerve allografts were cold preserved for 3 weeks. At
      periods of 3, 5, and 8 months after surgery, quantitative electrophysiological
      assessment and video recordings were performed. At the end of the study,
      quantitative analysis of neurons in the facial nucleus was carried out, and axons
      were stereologically counted. RESULTS: After the regenerative period, neuronal
      density was higher in the autograft group. However, distal axonal counts were
      similar in both groups. Serial electrophysiological recordings and histology of
      nerve allografts showed that the grafts were partially rejected after cessation
      of the immunosuppressant. CONCLUSION: The regeneration through nerve allografts
      temporarily treated with FK506 does not achieve the electrophysiological results
      and neuronal counts achieved with nerve autografts, but axonal collateralization
      in the allografts induces a similar activation of mimic muscles.

PMID- 16575342
TI  - Godfrey Hounsfield and the dawn of computed tomography.
AB  - OBJECTIVE: To provide a historical account of the events surrounding the
      development of the computed tomography scanner. METHODS: Information was obtained
      by interviewing people who worked with Sir Godfrey Hounsfield and Dr. James
      Ambrose at Atkinson Morley's Hospital in the 1970s, and from published books,
      articles, and several web sites, including the Nobel web site. RESULTS: The
      computed tomography scanner was successfully developed because of the
      collaboration between an imaginative engineer, Godfrey Hounsfield, who created
      the machine, and a brilliant neuroradiologist, James Ambrose, who demonstrated
      its wide clinical significance. CONCLUSION: The computed tomography scanner
      represents one of the most important contributions to neurosurgical practice in
      the past 100 years, and its development is a remarkable story of scientific
      endeavor.

PMID- 16575343
TI  - Genetic deafness in a preterm infant with a critical postnatal course.
AB  - OBJECTIVE: We present a case of deafness in a preterm infant with several
      predisposing factors of an acquired hearing impairment that, however, turned out
      to have a genetic cause. We describe the severe postnatal course and review the
      relevant literature. DESIGN: Case report. SETTING: University-based tertiary
      neonatal intensive care unit. PATIENT: Preterm infant (gestational age, 26/37;
      wks). MEASUREMENTS AND MAIN RESULTS: A preterm infant exhibited hearing
      impairment after a complicated clinical course with pneumothoraces, a
      hemodynamically relevant patent ductus arteriosus, treatment with potentially
      ototoxic drugs, intraventricular hemorrhage, and periventricular leukomalacia.
      Despite the absence of a family history for deafness, genetic testing was
      performed. Surprisingly, genetic analysis revealed the presence of two compound
      heterozygous mutations in the patient's GJB2 gene as the cause for his early
      onset nonsyndromic deafness. CONCLUSION: To elucidate the nature of a hearing
      disorder, it is worthwhile to consider a genetic cause, despite the fact that it
      may seem unlikely in a severely sick preterm infant with numerous risk factors
      for a postnatally acquired hearing impairment and without a positive family
      history.

PMID- 16575344
TI  - Dopamine infusion: a possible cause of undiagnosed congenital hypothyroidism in
      preterm infants.
AB  - OBJECTIVE: To describe the possibility that dopamine infusion can prevent early
      diagnosis of congenital hypothyroidism. DESIGN: Case report. SETTING: Medical
      neonatal intensive care unit of a tertiary academic medical center. PATIENTS: We
      report four preterm newborns affected by transient primary congenital
      hypothyroidism who showed low serum thyroxine and normal thyroid-stimulating
      hormone concentrations on primary screening performed during treatment with
      dopamine. INTERVENTIONS: Thyroid reevaluation screening after dopamine
      discontinuation. MEASUREMENTS AND MAIN RESULTS: Thyroid reevaluation showed
      elevated thyroid-stimulating hormone levels. CONCLUSION: We emphasize that
      dopamine capacity to suppress thyroid-stimulating hormone could prevent early
      diagnosis of congenital hypothyroidism. We suggest all newborns to be tested
      simultaneously for thyroid-stimulating hormone and thyroxine values at primary
      screening. A reevaluation of thyroid hormones after dopamine discontinuation is
      advisable in patients treated with dopamine.

PMID- 16575345
TI  - Uncuffed endotracheal tubes should not be used in seriously burned children.
AB  - OBJECTIVE: To document a complication associated with placement of uncuffed
      endotracheal tubes in seriously burned children. DESIGN: Retrospective review.
      SETTING: Verified pediatric burn center. PATIENTS/SUBJECTS: Acutely burned
      children requiring urgent replacement of uncuffed endotracheal tubes with cuffed
      endotracheal tubes over a 5-yr period. INTERVENTIONS: In all children, the reason
      behind the need for urgent tube change was uncontrollable air leak, despite
      properly sized uncuffed endotracheal tubes, as respiratory failure progressed and
      compliance worsened. RESULTS: : These two girls and three boys had an average age
      of 2.2 +/- 1.0 yrs, burn size of 41% +/- 6.1% of the body surface, and
      subsequently required mechanical ventilation for an average of 23.6 +/- 6.3 days.
      Urgent tube change was required an average of 64.2 +/- 43.8 hrs after arrival in
      the burn unit (87.6 +/- 49.4 hrs after injury). Although successful in all
      children, massive facial edema rendered tube change potentially dangerous. The
      intervention would not have been necessary if cuffed endotracheal tubes had been
      placed initially. All children went on to survive their injury, without further
      tube change or tracheostomy. CONCLUSION: If children are critically burned and
      expected to require more than transient mechanical ventilatory support, low
      pressure cuffed endotracheal tubes should be placed, regardless of the child's
      age.

PMID- 16575346
TI  - Evaluation of a noninvasive cardiac output monitor in mechanically ventilated
      children.
AB  - OBJECTIVE: To compare measurements of cardiac output (CO) and cardiac index (CI)
      obtained by a recently developed noninvasive continuous cardiac output system,
      NICO (CONICO), and transthoracic Doppler echocardiography (COTTE) in mechanically
      ventilated children. DESIGN AND SETTING: Prospective study in a university
      affiliated tertiary pediatric intensive care unit. PATIENTS: A total of 21
      mechanically ventilated children, weighing >15 kg, in stable respiratory and
      hemodynamic condition. MEASUREMENTS: Sets of three successive measurements of CO
      with the NICO system and transthoracic Doppler echocardiography were obtained.
      Bland-Altman analysis was used to compare the agreement between the two methods.
      RESULTS: The mean +/- sd CO values were 4.06 +/- 1.43 L/min for CONICO and 4.67
      +/- 1.78 L/min for COTTE. Bias +/- sd between the two methods was -0.61 +/- 0.94
      L/min. The variability of the difference between the two methods increased as the
      magnitude of the CO measurement increased. Similar results were obtained for
      cardiac index: 4.01 +/- 1.40 L.min.m for CINICO and 4.59 +/- 1.48 L.min.m for
      CITTE. Bland-Altman analysis revealed a nonuniform relationship between CI
      difference and the magnitude (y = -0.299 - 0.0655 x mean). The variability of the
      differences did not increase as the magnitude of the CO measurement increased (sd
      of estimate was 0.827 L.min.m). With both CONICO and CINICO, each measurement was
      highly repeatable, with coefficient of variation of only 2.88% +/- 2.31%.
      Repeatability with Doppler echocardiography was 7.02% +/- 4.33%. CONCLUSIONS: The
      NICO system is a new device that measures CO easily and automatically in
      mechanically ventilated children weighing >15 kg. CO values obtained with this
      technique were in agreement with those obtained with Doppler echocardiography in
      children in respiratory and hemodynamic stable condition. The NICO system needs
      further investigation in children in unstable respiratory and hemodynamic
      condition.

PMID- 16575347
TI  - Fatal cerebral edema from late-onset ornithine transcarbamylase deficiency in a
      juvenile male patient receiving valproic acid.
AB  - OBJECTIVES: The aims of this report are to 1) present a rare case of fatal
      cerebral edema associated with late-onset ornithine transcarbamylase (OTC)
      deficiency in a juvenile male patient receiving valproic acid and 2) review the
      neuropathologic changes associated with the hyperammonemia. DESIGN: Case report.
      SETTING: A community hospital and a tertiary pediatric critical care unit.
      INTERVENTIONS: Carbohydrate administration, intravenous nitrogen excretion
      cocktail, and high-flux hemodialysis. MEASUREMENTS AND MAIN RESULTS: Despite
      aggressive therapy for presumed late-onset OTC deficiency, the patient rapidly
      developed fatal cerebral edema with tonsillar herniation. A liver biopsy
      confirmed OTC deficiency with approximately 3% of residual hepatic enzyme
      activity. Chromosomal analysis showed a normal male karyotype. A thorough
      molecular analysis of the coding region in the OTC gene Xp21.1 was completed, but
      mutations were not identified, suggesting an upstream or downstream abnormality.
      Severe brain swelling was evident on neuropathology, and histopathology showed
      Alzheimer type II astrocytes, neuronal cytoplasmic changes, and hypertrophy and
      eosinophilia of the small arterial walls. CONCLUSIONS: OTC deficiency is the most
      common urea cycle defect causing hyperammonemia. Late-onset presentations of OTC
      are infrequent, primarily affecting female patients. We present a rare case of a
      late-onset OTC deficiency in a juvenile male patient receiving valproic acid
      therapy who developed fatal cerebral edema. Valproic acid exacerbates acute
      elevations in ammonia and may contribute synergistically with ammonia to cerebral
      mitochondrial dysfunction.

PMID- 16575348
TI  - Octreotide efficacy in the treatment of chylothoraces following cardiac surgery
      in infants and children.
AB  - OBJECTIVE: To examine the efficacy of octreotide in resolving chylothoraces in
      infants and children following cardiac surgery. DESIGN: Retrospective chart
      review. SETTING: Pediatric intensive care unit of a tertiary care center.
      PATIENTS: All children who received octreotide for the treatment of chylothoraces
      following surgery for congenital heart disease over a 30-month period between
      2001-2004. INTERVENTIONS: Octreotide infusion. MEASUREMENTS AND MAIN RESULTS:
      Eight courses of octreotide treatment were identified in seven patients who met
      our inclusion criteria. The median duration of therapy was 5 days, and dosing
      ranged from 1 to 4 microg/kg/hr. Treatment did not result in an overall decrease
      in average chest tube output after 3 days of therapy. However, in two patients
      (29%) the chylothoraces ultimately resolved during the octreotide infusion.
      Treatment was well tolerated, and no serious side effects were noted. CONCLUSION:
      In contrast to previously published reports, we find octreotide therapy for
      postoperative chylothoraces to be successful in only a minority of cases.

PMID- 16575349
TI  - Serial circulating vasopressin levels in children with septic shock.
AB  - BACKGROUND: Septic shock is an important cause of death in pediatric intensive
      care units. Initial evaluations have shown that vasopressin may have a role in
      catecholamine refractory shock in adults. It is important to determine whether
      children with septic shock have deficiency of vasopressin. This will help in
      defining the role of vasopressin in septic shock. DESIGN: Prospective cohort
      study. SETTING: Pediatric intensive care unit of a tertiary care hospital in
      north India. PATIENTS: Patients were children with septic shock, and controls
      were children with sepsis but no shock. STUDY DESIGN: Vasopressin levels in
      plasma were determined by enzyme-linked immunosorbent assay for children with
      septic shock at diagnosis (baseline) and thereafter at 24, 48, and 96 hrs to
      determine the time trends. The baseline vasopressin values for children with
      septic shock were compared with those for children without shock. RESULTS: The
      median (95% confidence interval) vasopressin level at baseline in children with
      septic shock was 116 (63.3-130.7) pg/mL, and in children with sepsis but no shock
      it was 106 (61.7-131.77) pg/mL. The median value for survivors was 76 (44.6
      130.9) pg/mL, and for nonsurvivors, 118 (81.7-259) pg/mL (p = .16). The serial
      values also did not show any significant changes; the values at 24 hrs (n = 17),
      48 hrs (n = 16), and 96 hrs (n = 15) were 105 (76.1-125.9), 105 (41.4-155.5), and
      109.5 (54.9-154.8) pg/mL, respectively. CONCLUSIONS: The results of our study
      suggest that vasopressin levels are elevated in children with septic shock and
      that serial values up to 96 hrs do not show any decline.

PMID- 16575350
TI  - Posttraumatic pseudoaneurysm of the intracavernous internal carotid artery
      presenting with massive epistaxis.
AB  - OBJECTIVES: To report a case of posttraumatic pseudoaneurysm of the
      intracavernous internal carotid artery presenting with massive epistaxis and to
      discuss its pathophysiology and management. DESIGN: Case report and literature
      review. SETTING: Pediatric intensive care unit in a tertiary-care center.
      PATIENTS AND RESULTS: Twelve days after a motor vehicle accident causing a head
      injury and facial fractures, this patient presented with massive epistaxis due to
      a pseudoaneurysm of the intracavernous internal carotid artery . Nasal packing
      was performed and subsequent angiography demonstrated the vascular lesion that
      had dissected into the sphenoid sinus. Endovascular stent and coil occlusion of
      the vascular lesion was performed, and the patient's condition improved without
      any ischemic or thromboembolic sequelae. CONCLUSION: Posttraumatic aneurysms of
      the intracavernous internal carotid artery can be associated with delayed and
      sometimes lethal massive epistaxis. This vascular lesion should be considered in
      patients with traumatic brain injury presenting with basal skull fractures in the
      region of the carotid canal or cavernous sinus and/or orbital fractures and
      compromise of the optical nerves. Knowledge of these risk factors and early
      diagnosis can minimize the high mortality risk.

PMID- 16575351
TI  - Fatal pulmonary fat embolism following spinal fusion surgery.
AB  - OBJECTIVE: To report the case of a fatal pulmonary fat embolism as a complication
      of spinal fusion surgery. DESIGN: Case report. SETTING: Pediatric intensive care
      unit at a freestanding tertiary care children's hospital. PATIENT: An adolescent
      female with neuromuscular scoliosis who underwent spinal fusion surgery with
      instrumentation and suffered a fatal pulmonary fat embolism. CONCLUSION: Spinal
      fusion surgery for neuromuscular scoliosis is a common operative procedure.
      Pulmonary fat embolism as a complication of this procedure is rare. This case
      emphasizes the need to be aware of this potentially fatal postoperative
      complication. Specifically evaluating for this rare complication may lead to
      understanding cases of unexplained deterioration and death.

PMID- 16575352
TI  - Severe ischemia of the lower limb and of the intestine associated with systemic
      vasoconstrictor therapy and femoral arterial catheterization.
AB  - OBJECTIVE: To report a case of peripheral and intestinal ischemia associated with
      arterial catheterization and terlipressin treatment in a child. DESIGN: Case
      report. SETTING: Pediatric intensive care unit of a university hospital. PATIENT:
      The patient was a 2-month-old female infant with shock refractory to treatment
      with catecholamines, who received treatment with terlipressin (20 microg/kg/4
      hrs). In order to monitor her cardiac output, the right femoral artery was
      catheterized with a 4-Fr PiCCO catheter. At 60 hrs, the patient presented
      progressive ischemia of the right lower limb and intestinal ischemia. The
      ischemia did not improve despite withdrawal of the catheter and interruption of
      the terlipressin administration; it progressed to massive intestinal ischemia,
      and the patient died. CONCLUSIONS: Arterial catheterization combined with the
      administration of vasoconstrictor drugs, particularly vasopressin or
      terlipressin, can lead to local ischemic complications and severe intestinal
      ischemia in infants in shock.

PMID- 16575353
TI  - The use of enteral naloxone to treat opioid-induced constipation in a pediatric
      intensive care unit.
AB  - OBJECTIVE: To describe the effects of enteral naloxone used to treat opioid
      induced constipation in pediatric intensive care patients. DESIGN: Retrospective
      chart review. SETTING: Pediatric intensive care unit. PATIENTS: Twenty-three
      patients who received opioid therapy and enteral naloxone in our institution from
      January 2003 to February 2004 were compared with a randomly sampled control group
      matched for age, weight, sex, and length of stay who received opioids but had not
      received enteral naloxone. INTERVENTIONS: None. MEASUREMENTS: Daily stool output,
      daily opiate usage, nutrition, adjuvant laxative use, and side effects were
      assessed. RESULTS: Patients stayed an average of 5 days (range, 0-13 days) in the
      pediatric intensive care unit before enteral administration of naloxone was
      instituted and received it for an average of 9 consecutive days (range, 3-30
      days). Mean stool output for study patients before administration of enteral
      naloxone was 0.14 +/- 0.38 stools per day, whereas after its initiation it was
      1.60 +/- 1.14 stools per day (p < .001). However, two patients developed
      significant opiate withdrawal symptoms after receiving enteral naloxone. The
      average stool output for control patients was 0.53 +/- 1.21 stools per day.
      CONCLUSIONS: Enteral naloxone may be effective in increasing stool output in
      opioid-induced constipation but carries the risk of introducing withdrawal
      symptoms. Further studies are needed to evaluate this agent for opioid-induced
      constipation in the intensive care unit.

PMID- 16575355
TI  - Decreasing errors in pediatric continuous intravenous infusions.
AB  - OBJECTIVE: To evaluate the effect of a Web-based calculator and decision-support
      system on infusion ordering errors and to estimate error frequency in pharmacy
      infusion preparation. DESIGN: Data on ordering error frequency and typology were
      collected before and after implementation of an online infusion ordering system.
      Data on pharmacy preparation errors of infusions were collected. SETTING: A
      children's hospital at an academic medical center. PATIENTS: None. Data were
      abstracted from infusion orders. INTERVENTIONS: Introduction of a voluntary-use
      Web-based calculator into infusion ordering workflow. Observation only. MAIN
      OUTCOME MEASURES: Number and type of errors in handwritten and calculator
      generated orders. Number and type of errors in pharmacy infusion preparation.
      RESULTS: Before calculator deployment, 129 sequential handwritten infusion orders
      were collected over 5 weeks. After deployment, of 162 sequential infusion orders,
      88% (142) were calculator-generated. Calculator-generated infusion orders
      contained 83% fewer (p < .001) orders containing one or more errors than
      handwritten orders. Calculator-generated orders contained no high-risk errors
      (incorrect decimal, dose, or unit of measure) when compared with handwritten
      orders and were associated with fewer pharmacy interventions. In 118 sequential
      pharmacy infusion preparations over 4 wks, there were no errors observed.
      CONCLUSION: A Web-based calculator reduced significantly the total number of
      errors and eliminated all high-risk errors in the prescribing process for
      continuous pediatric infusions. With no observed errors in pharmacy preparation,
      this study provides data to support the use of computerized ordering as an
      independent safe and viable method for ordering continuous pediatric infusions.

PMID- 16575354
TI  - ENHANCE: results of a global open-label trial of drotrecogin alfa (activated) in
      children with severe sepsis.
AB  - OBJECTIVE: To gather additional 28-day all-cause mortality data and safety
      information for pediatric patients with severe sepsis who received drotrecogin
      alfa (activated) (DrotAA). DESIGN AND SETTING: Single-arm, open-label,
      multicentered study conducted in 59 study sites in 15 countries. PATIENTS: One
      hundred eighty-eight children (term newborn to <18 yrs old) with severe sepsis
      were consecutively enrolled in the study. INTERVENTION: Administration of DrotAA,
      24 microg/kg/hr for 96 hrs. MAIN OUTCOME MEASURES: Four-day and 28-day all-cause
      mortality, safety information, and protein C levels. RESULTS: : One-hundred
      eighty-seven patients completed the study. The 4-day mortality rate was 7.0%, and
      the 28-day mortality rate was 13.4%. At baseline, 57.6% of patients were severely
      deficient in protein C (a level < or = 40% of normal). There was a statistically
      significant association between increased 28-day mortality and decreased end-of
      infusion protein C levels (p < .001), greater number of baseline organ
      dysfunctions (p < .001), and greater baseline ventilator use (p = .03). Bleeding
      was the most significant complication observed. Serious bleeding events
      (including anemia without a bleeding source) were experienced by 27.7% of
      patients (n = 52). Six of the serious bleeding events (3.2%) were considered
      related to administration of DrotAA. During infusion, serious bleeding events
      with an identified source of bleeding were experienced by 5.9% of patients (n =
      11). Central nervous system bleeding was experienced by 2.7% (n = 5). Two of the
      intracranial hemorrhages were fatal and occurred postinfusion. CONCLUSIONS:
      Without a placebo control, no efficacy conclusions are possible. Subgroups at
      higher risk of death were identified, and the change in protein C level from
      baseline was predictive of survival. The most significant complication observed
      was bleeding. Risk factors for serious bleeding appear to be multiple organ
      failure, thrombocytopenia, and coagulopathy.

PMID- 16575356
TI  - [The International Center for Cancer Research (CIRC), the pill, CNGOF, FNCGM, and
      the SFG].

PMID- 16575358
TI  - [Laparoscopy and gynecologic cancer in 2005].
AB  - All the surgical procedures, which may be required to treat a gynecologic cancer,
      can be performed endoscopically. However prospective randomized studies required
      to confirm the oncologic efficacy of the technique are still lacking in
      gynecology, whereas such studies are available in digestive surgery. Animal
      studies suggested that the risk of tumor dissemination in non traumatized
      peritoneum is higher after a pneumoperitoneum than after a laparotomy.
      Experimental studies also emphasized two points: the surgeon and the surgical
      technique are essential, all the parameters of the pneumoperitoneum may influence
      the postoperative dissemination. Changing these parameters we may, in the future,
      be able to create a peritoneal environment adapted to oncologic patients in order
      to prevent or to decrease the risks of peritoneal dissemination and/or of
      postoperative tumor growth. Until the results of prospective randomized studies
      become available, the preoperative selection of the patients and the surgical
      technique should be very strict. In patients with endometrial cancer, the
      laparoscopic approach should be reserved to clinical stage I disease, if the
      vaginal extraction is anticipated to be easy accounting for the volume of the
      uterus and the local conditions. In cervical cancer, the laparoscopic approach
      should be reserved to patients with favorable prognostic factors: stage IB of
      less than 2 cm in diameter. Laparoscopy is the gold standard for the surgical
      diagnosis of adnexal masses. But the puncture should be avoided whenever
      possible. The surgical treatment of invasive ovarian cancer should be performed
      by laparotomy whatever the stage. In contrast restaging of an early ovarian
      cancer initially managed as a benign mass, is a good indication of the
      laparoscopic approach. The laparoscopic management of low malignant potential
      tumors should include a complete staging of the peritoneum. Knowledge of the
      principles of endoscopy and of oncologic surgery is required. Teaching and
      diffusion of endoscopic oncological techniques are among the major challenges of
      gynecologic surgery within the next few years.

PMID- 16575359
TI  - [Laparoscopic pelvic exenteration for cervical cancer relapse: preliminary
      study].
AB  - OBJECTIVES: To determine the feasibility and short and midterm results of
      laparoscopic pelvic exenteration for cervical cancer relapse. Materials and
      methods. Five patients with centro-pelvic recurrence within 3 to 13 months after
      combined chemo-radiation therapy (associated to surgery for two cases) for
      cervical cancer tumors were included in a pilot study. RESULTS: The procedures
      consisted in a complete pelvic exenteration with colo-anal anastomosis and ileal
      loop conduit for 2 patients, a posterior pelvic exenteration including uterus,
      vagina and rectum with colo-anal anastomosis for 1 patient, an anterior pelvic
      exenteration including bladder and vagina with an ileal-loop conduit for 1
      patient and a anterior pelvic exenteration with a laparoscopic hand assisted
      Miami Pouch for 1 patient. The 5 procedures were successful with no conversion to
      laparotomy. Time of procedure ranged between 4 h 30 and 9 hours. Average blood
      loss was 370 cc. Three patients developed metastatic recurrences and died. The
      two patients with anterior exenteration are alive and free of disease 11 and 15
      months after the procedure. CONCLUSION: Laparoscopic pelvic exenteration
      procedures are feasible. A larger series is necessary to determine the advantages
      of this technique compared to laparotomy.

PMID- 16575360
TI  - [Obstetrical management of patients at risk of neonatal lupus syndrome: review of
      the literature].
AB  - Fetuses and infants of women with anti-SSA/Ro and anti-SSB/La antibodies are at
      risk of neonatal lupus syndrome, featuring skin lesions, hematological and
      hepatic disorders, and congenital heart block (CHB) in the absence of severe
      cardiac malformation. The prevalence of CHB in newborns of anti-SSA/Ro positive
      women with known connective tissue disease is 1 to 2% and the risk of recurrence
      ranges from 10 to 17%. CHB is definitive and is associated with significant
      morbidity (pacemaker must be implanted in 2/3 of cases) and mortality (16 to
      19%). Myocardial involvement may either be associated or appear subsequently.
      Other manifestations are discussed. For anti-SSA/Ro positive pregnant women,
      echocardiograms should be performed every 2 weeks from 16 to 24 weeks of
      gestation, and every week in case of past history of CHB. Electrocardiogram
      should be performed in the first days of life for all children to detect
      incomplete CHB. Therapy for CHB detected in utero is based on fluorinated
      steroids, especially betamethasone. Its efficiency is variable.

PMID- 16575361
TI  - [Immediate complications of surgical abortion].
AB  - While medical abortion is now available in non hospital facilities, abortions by
      vacuum aspiration remain illegal in non hospital settings. It is therefore
      important to assess through the literature the real risks associated with this
      method. All the most recent and large-scale studies showed that legal abortion by
      vacuum aspiration is an extremely safe procedure. It is less risky than other
      medical or surgical procedures performed outside the hospital. According to the
      studies, the death rate varies from 0 to 0.7 per 100,000 abortions, and is
      smaller when the procedure is done under local anesthesia than general
      anesthesia. The overall early complication rate (hemorrhage, uterine perforation,
      cervical injury) is between 0.01 and 1.16%. Complications are not more frequent
      than with medical abortions. In view of these low complication rates, surgical
      abortion by vacuum aspiration could be performed outside the hospital setting in
      France, as it is the case in many other countries.

PMID- 16575362
TI  - [More on compensation of the handicapped child].
AB  - By adopting a heading enTITREd "solidarity towards handicapped people" within the
      French law dated March 4, 2002 on health reform, the government hoped to put an
      end to the controversy that ensued after the so-called "Perruche" ruling. Since
      then, several rulings have been given by administrative jurisdictions and it
      seems that debate in this area is far from over. The first point developed
      concerns issues raised about the concept of 'characterized malpractice'
      introduced under this law, the only type of malpractice that may render a doctor
      liable. A ruling by the Council of State on February 19, 2003 and two decisions
      by the Administrative Appeal Courts dated February 19 and April 20, 2004 gave an
      answer. Recent decisions, namely a ruling by the Council of State dated February
      9, 2005, seem to confirm this impression. Characterized malpractice that can
      render a doctor liable is not gross neglect but rather neglect that is simple,
      certain and cannot be contested. However, due to its intensity and its proof,
      this type of neglect is more than just ordinary negligence. The second point
      discussed is the limitation of parents' compensable hardship attributable to
      medical malpractice. The law dated March 4, 2002 limited this compensation
      "solely to parents' hardship" to the exclusion of expenses incurred as a result
      of the child's handicap. National solidarity, which was intended to absorb this
      expense, is taking some time to become apparent. The legal decisions given since
      2002 have thus brought about a certain level of unease both in public opinion and
      the legal profession. In June 2003, the Parisian Court of Appeal gave a
      surprising but apt ruling that may nevertheless bring certain concerns to the
      surface. To our knowledge, the Council of State has yet to issue an opinion on
      this subject. Doctors' liability in terms of the birth of child born with a
      congenital handicap is still a possibility.

PMID- 16575363
TI  - [Sjogren syndrome in Obstetric and Gynecology: literature review].
AB  - Sjogren syndrome (SS) is an immune disease characterized by a progressive
      degeneration of exocrine glands. It leads to dryness of mucosa and
      conjunctivitis. Gynecologists and obstetricians may encounter this disease in
      women at any age, including during pregnancy. Knowledge of the main
      characteristics is required for early diagnosis and multidisciplinary program. In
      the event of secondary Sjogren syndrome occurring during pregnancy, treatment
      focuses on the associated disease, mainly systemic lupus erythematosus. In
      primary Sjogren syndrome, pregnancy does not appear to influence disease course.
      However, patients with both primary and secondary Sjogren syndrome must be
      monitored carefully. There is a risk of neonatal lupus and congenital
      atrioventricular bloc associated with high morbidity and mortality. These
      patients should benefit from multidisciplinary care in a hospital with a neonatal
      intensive care unit.

PMID- 16575364
TI  - [Contribution of fetal middle cerebral artery peak systolic velocity in the
      management of non-immune hydrops].
AB  - Hydrops fetalis is associated with a wide variety of fetal and maternal
      disorders. Among these disorders, cases with anemia may benefit from a specific
      treatment. The authors report on two cases of hydrops fetalis with increased
      middle cerebral artery peak systolic velocity and discussed the contribution of
      this finding in the management of fetuses with hydrops.

PMID- 16575365
TI  - [Prenatal diagnosis of sirenomelia].
AB  - Sirenomelia sequence associates a fusion of inferior legs with renal anomalies
      until bilateral agenesis. It is a rare and lethal polymalformation. The purpose
      of the ultrasonographic study is to identify the sirenomelia as early as possible
      during pregnancy and to differentiate it from caudal regression syndrome. A case
      of sirenomelia diagnosed early is reported together with a review of the
      literature. The ultrasonographic diagnosis, associated defects, the interest of
      color Doppler study of abdominal vasculature are discussed. Antenatal
      ultrasonographic diagnosis should be obtained as early as possible, before 20th
      gestational week at the latest. Color Doppler is helpful to confirm the diagnosis
      in case of bilateral renal agenesis. The main differences between sirenomelia and
      caudal regression syndrome (which requires a very different genetic counselling)
      are summarized in a table.

PMID- 16575366
TI  - [Malignant transformation of abdominal wall endometriosis: a new case report].
AB  - Cancer arising in abdominal wall endometriosis is a rare event, hindering
      diagnosis and making management uncertain. A cesarean section scar is generally
      at the origin of the disease. We report the case of a 45-year-old woman, with a
      past medical history of cesarean deliveries, complaining of a repeat abdominal
      wall endometriosis which transformed into a clear-cell carcinoma. Outcome was
      rapidly fatal. Compared with endometriosis-associated ovarian carcinoma, the
      prognosis of this abdominal scar complication is poor. In the literature,
      survival rate reaches only 57% after a short follow-up of 20 months. Clear-cell
      carcinoma is the most common histological subtype, followed by endometrioid
      carcinoma. Radical surgery is the main treatment. Good technique and proper care
      during cesarean section may help in preventing this endometriosis complication.

PMID- 16575367
TI  - [Pregnancy after transobturator insertion of a suburethral sling: a case report
      and review of the literature].
AB  - Rare cases of pregnancy occur after surgical treatment of an urinary
      incontinence. We report the case of a 37-year-old patient became pregnant 5
      months after trans-obturator insertion of a suburethral sling (Monarc). The
      pregnancy was monitored regularly and no sign of urinary incontinence was
      observed. Caesarean delivery was decided at 40 weeks gestation. The patient has
      remained quite continent, one year after delivery. The appropriate mode of
      delivery is discussed.

PMID- 16575368
TI  - [About: "Early prophylactic cervical cerclage for hypoplastic cervix following
      exposure to DES in utero" (J Gynecol Obstet Biol Reprod, n 6-2005)].

PMID- 16575369
TI  - [About: "Decision-to-deliver interval for forceps delivery and cesarean
      section"(J Gynecol Obstet Biol Reprod, n 8-2005)].

PMID- 16575370
TI  - [About: "Instrumental extraction with Thierry's spatula" (J Gynecol Obstet Biol
      Reprod, n 8-2005)].

PMID- 16575372
TI  - Making a diagnosis when one is not apparent: bridging the gap between somatic
      patient and frustrated physician.

PMID- 16575371
TI  - [About: "Prevention of fetomaternal anti-D alloimmunization: should should
      noninvasive fetal genotyping be instituted now?" (J Gynecol Obstet Biol Reprod, n
      1-2006)].

PMID- 16575373
TI  - Pramipexole: augmentation in the treatment of depressive symptoms.
AB  - We describe a retrospective case series of three patients, two with bipolar
      depression and one with unipolar depression. Pramipexole is a Food and Drug
      Administration-approved antiparkinsonian agent, which, when used to augment
      antidepressants, would be considered an off-label use and should be discussed
      with the patient. These patients had robust responses to pramipexole augmentation
      of their treatment regimen. All three patients had been taking an atypical
      antipsychotic. The depressive symptoms were evaluated using the Hamilton Rating
      Scale for Depression.

PMID- 16575374
TI  - A discrimination based on autogenous versus reactive obsessions in obsessive
      compulsive disorder and related clinical manifestations.
AB  - INTRODUCTION: Although putative subtypes of obsessive-compulsive disorder (OCD)
      have been gradually more recognized, there is no generally accepted subtype
      discrimination. It has been suggested that autogenous and reactive obsessions
      stem from different cognitive process. This study aimed to assess existence of
      gender, age at onset of illness, and comorbidity differences in OCD patients
      suffering from autogenous and reactive obsessions. METHODS: The medical records
      of 177 OCD patients were evaluated retrospectively for gender, age at onset,
      comorbid diagnoses, and predisposing life events. Obsessions and compulsions were
      coded according to the Yale-Brown Obsessive-Compulsive Scale. All patients were
      grouped as the patients with autogenous (autogenous group [AG] n=32), reactive
      (reactive group [RG] n=77) and mixed obsessions (mixed group [MG] n=68). RESULTS:
      AG patients were significantly more likely to be male, compared with the RG and
      MG patients. They also had significantly later onset of illness. Dissociative
      disorders were less common among AG patients compared with the other groups.
      CONCLUSION: Results suggest that the discrimination between autogenous and
      reactive obsessions are not only based on their development and maintenance
      mechanism through different cognitive process but that there also clinical
      manifestations of this discrimination.

PMID- 16575376
TI  - The potentially somatizing effect of clinical consultation.
AB  - Many patients who present physical symptoms that their doctors cannot explain by
      physical disease have persisting symptoms and impairment. An influential view has
      been that such symptoms are the somatization of emotional distress, but there has
      also been concern that medical practice contributes to shaping these
      presentations. Analysis of patients' accounts indicate that they approach these
      consultations with a sense of being the expert on the nature and reality of their
      symptoms and, in primary care at least, they seek convincing explanations,
      engagement, and support. They often describe doctors as doubting that their
      symptoms are real and as not taking their symptoms seriously. Observational
      research has demonstrated that patients presenting idiopathic symptoms in primary
      care generally provide cues to their need for explanation or to psychosocial
      difficulties. Their doctors tend to provide simple reassurance rather than
      detailed explanations, and often disregard psychosocial cues. Patients seem to
      intensify their presentation in consequence, elaborating and extending their
      accounts of their symptoms, perhaps in the effort to engage their doctors and
      demonstrate the reality of their symptoms. When doctors propose physical
      investigation and treatment in response to such escalating presentation, they
      thereby inadvertently somatize patients' psychological presentation.
      Consultations, therefore, have elements of contest, whereby patients seek
      engagement from doctors who seek to disengage. Although provision of a medical
      label, such as a functional diagnosis, can legitimize patients' complaints and
      avoid contest, this is at the risk of indicating that medicine can take
      responsibility for managing the symptoms. More collaborative relationships rely
      on doctors recognizing patients' authority in knowing about their symptoms, and
      providing tangible explanations that make sense to the patient and allow them to
      tolerate or manage the symptoms. Researchers need to study how doctors can best
      achieve these aims within routine consultations.

PMID- 16575377
TI  - Idiopathic physical symptoms: a common manifestation of psychiatric disorders in
      primary care.
AB  - Worldwide, patients with common mental disorders, such as depression and anxiety,
      have a tendency to present first to primary care exhibiting idiopathic physical
      symptoms. Typically, these symptoms consist of pain and other physical complaints
      that remain medically unexplained. While in the past, traditional psychopathology
      emphasized the relevance of somatic presentations for disorders, such as
      depression, in the last few decades, the "somatic component" has been neglected
      in the assessment and treatment of psychiatric patients. Medical specialties have
      come up with a variety of "fashionable" labels to characterize these patients and
      the new psychiatric nomenclatures, such as the Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Edition, attempt to classify these patients into a
      separate "somatoform disorders" category. These efforts fall short, and
      revisionists are asking altogether for the elimination of "somatoform disorders"
      from future nomenclatures. This review emphasizes the importance of idiopathic
      physical symptoms to the clinical phenomenology of many psychiatric disorders,
      offers suggestions to the diagnostic conundrum, and provides some hints for the
      proper assessment and management of patients with these common syndromes.

PMID- 16575378
TI  - Antidepressants and cognitive-behavioral therapy for symptom syndromes.
AB  - Somatic symptoms are common in primary care and clinicians often prescribe
      antidepressants as adjunctive therapy. There are many possible reasons why this
      may work, including treating comorbid depression or anxiety, inhibition of
      ascending pain pathways, inhibition of prefrontal cortical areas that are
      responsible for "attention" to noxious stimuli, and the direct effects of the
      medications on the syndrome. There are good theoretical reasons why
      antidepressants with balanced norepinephrine and serotonin effects may be more
      effective than those that act predominantly on one pathway, though head-to-head
      comparisons are lacking. For the 11 painful syndromes review in this article,
      cognitive-behavioral therapy is most consistently demonstrated to be effective,
      with various antidepressants having more or less randomized controlled data
      supporting or refuting effectiveness. This article reviews the randomized
      controlled trial data for the use of antidepressant and cognitive-behavior
      therapy for 11 somatic syndromes: irritable bowel syndrome, chronic back pain,
      headache, fibromyalgia, chronic fatigue syndrome, tinnitus, menopausal symptoms,
      chronic facial pain, noncardiac chest pain, interstitial cystitis, and chronic
      pelvic pain. For some syndromes, the data for or against treatment effectiveness
      is relatively robust, for many, however, the data, one way or the other is
      scanty.

PMID- 16575379
TI  - Explanatory and pragmatic perspectives regarding idiopathic physical symptoms and
      related syndromes.
AB  - In recent years, research-methods literature mainly addressing controlled
      clinical trials has arisen regarding explanatory and pragmatic treatment trials.
      Explanatory trials tend to examine causal mechanisms and questions of efficacy
      and value internal validity (creating optimal study conditions) over
      generalizability (using study results to understand treatment effects in real
      life patient populations). In contrast, pragmatic trials value "external
      relevance" (generalizability) of study results over "internal elegance" so that
      clinicians and health policymakers can better understand how treatments might
      impact their patients and policies. This review draws inspiration from these
      contrasting explanatory and pragmatic perspectives and develops them for clinical
      and research pertaining to idiopathic physical symptoms and related syndromes
      (eg, somatization disorder, chronic fatigue syndrome, multiple chemical
      sensitivities, irritable bowel syndrome). Explanatory and pragmatic perspectives
      are used to examine these idiopathies with regard to causation, case definition,
      labels, and treatment. It is concluded that idiopathic symptom syndromes are
      fundamentally pragmatic clinical and research challenges. For epidemiologic and
      methodologic reasons, the complex explanations for these syndromes remain largely
      elusive. Even so, scientific and clinical pragmatism offers the opportunity to
      reduce disagreement between competing medical disciplines and between clinicians
      and affected patients with regard to irreconcilable etiologic questions and to
      remain evidence-based in the care of patients.

PMID- 16575381
TI  - The importance of splinting of teeth in the therapy of periodontitis.
AB  - AIM: The deep periodontal disease often leads to dental mobility with further
      aggravation of the symptomatology. The aim of the paper is to verify the
      importance of splinting of teeth in the therapy of periodontitis on the basis of
      parameters commonly studied [probing depth (PD), bleeding on probing (BOP),
      plaque index], and the role of the occlusal trauma as primary factor or second
      leading factor in periodontal diseases. METHODS: Thirty patients suffering from
      periodontitis have been treated with the splinting of teeth, neither preceded nor
      followed from topical and systemic pharmacological therapy, nor from surgical or
      non surgical treatment of the periodontal tissues involved. During the 4 visits
      provided by the study, T0 (0 days), T1 (30 days), T2 (90 days) and T3 (180 days),
      PD, BOP and plaque index have been estimated. RESULTS: From the comparison of the
      T0 PD and BOP with the T3 PD and BOP, a significant improvement of these
      parameters is observed (P<0.05). CONCLUSION: On the basis of the clinical data
      obtained in this research, the authors suggest that the therapy by means of
      splinting improves the prognosis of teeth affected by periodontal disease;
      occlusal trauma and dental mobility cause the aggravation of periodontal lesions.

PMID- 16575382
TI  - Neurosedation in dentistry of the disabled patient: the use of midazolam,
      propofol, and remifentanil.
AB  - AIM: This prospective randomized study, deals with neurosedation in dental
      treatment of 200 disabled patients and unable to cooperate, subdivided in 4
      groups of 50 male only patients, with age ranging from 28 to 59 (39+/-11), ASA I
      III. METHODS: The pharmaceuticals used were Midazolam (group MID) Propofol (group
      Prop) and Remifentanil. Midazolam and Propofol were used following a bolus
      infusion sequence, both separately and in combination among themselves (MID?PROP
      group), or with an opioid, Remifentanil (MID?PROP?REMI group). ECG, heart rate ,
      non invasive blood pressure (NIBP), SaO(2), EtCO(2) during the procedure were
      monitored. Induction time, duration of the sedation, recovery time and discharge
      were reported. RESULTS: The statistical analysis demonstrated the superiority of
      the PROP group for induction time in minute (3.1+/-0.5) in comparison with the
      MID group (10.6+/-2.1), the MID?PROP group (4.3+/-1.3) and MID?PROP?REMI (3.7+/
      1.2). The recovery and discharge times have confirmed the superiority of the
      MID?PROP?REMI group in comparison with the other 3 groups. CONCLUSION: This
      combination proved best at leveraging the synergistic characteristics of each
      single pharmaceutical and minimizing the collateral effects of each individually.

PMID- 16575383
TI  - Nickel ions release in patients with fixed orthodontic appliances.
AB  - AIM: The extent to which orthodontic appliances can cause contact allergies due
      to nickel release is a controversial matter. Since the data provided by
      literature are contrasting, the Authors think that it is important to analyse
      nickel ions released in organic tissues by means of a plasma spectrometer.
      METHODS: About 100 intact hairs were taken from 15 patients wearing fixed
      orthodontic appliances. The hairs had been washed 12 to 24 h before, in order to
      limit environmental contamination. The same procedure was carried out on a
      control group corresponding in sex, age and abode. The samples of hair were taken
      from at least 3 different scalp sites: frontal, vertex and occipital areas.
      RESULTS: According to the spectrophotometric analysis of the hair, there were no
      differences in nickel concentrations between the test group (0.50 mg/g on
      average) and control group (0.64 mg/g) (*P<0.005). The mean value was reduced
      even further if minimum and maximum values were excluded (test group 0.46 mg/g,
      control group 0.52 mg/g). Even though there was a slight difference (0.14 mg/g),
      it showed that more nickel concentration was found in the control sample (without
      orthodontic appliances) to a maximum of 2.20 mg/g. This suggests that
      environmental contamination, in particular diet, has an influence on ion
      concentration. Other studies also confirm that gut absorption of nickel released
      in the mouth by orthodontic appliances is much lower than the absorption of
      nickel release through diet. CONCLUSIONS: It can be assumed that orthodontic
      appliances do not release significant values of nickel to be a risk factor to the
      patient's health.

PMID- 16575384
TI  - The use of mineral trioxide aggregate in endodontics.
AB  - Mineral trioxide aggregate (MTA), composed mainly of tricalcic silicate,
      tricalcic alluminate, bismuth oxide, is a particular endodontic cement. It is
      made of hydrophilic fine particles that harden in the presence of dampness or
      blood. It is biocompatible, radiopaque and it is harder to infiltrate, compared
      to classic materials for root filling such as amalgam, cements, Super-EBA, and
      IRM. and SEM studies of sections and copies in resin of root neoapices filled
      with amalgam, IRM, Super-EBA and MTA, as well as tests of microinfiltration have
      shown that MTA has excellent sealing capacities. It requires a working time of
      about 5 min and a hardening time that varies from 2 h and 45 min to 4 h according
      to the density of the air entrapped during mixing and the dampness of the
      receiving site. The long hardening time reduces internal tensions and the
      incidence of marginal infiltration, but it forces to definitively fill the tooth
      in the following sitting, with an interval of at least 3 days from the MTA
      application. Clinical experience shows how MTA is a material of choice in cases
      not only of endodontic surgery, apicectomy and retrograde filling but also in the
      sealing filling of perforations of the pulp chamber and of the root, stripping,
      internal reabsorptions, readaptations, lacerations, and apical transports. It has
      been used with success also in direct cappings and in apexifications instead of
      calcium hydroxide, leading to quicker therapies and more predictable RESULTS: The
      authors outline the operative phases of the different treatments proposed, make a
      survey of the most important studies published so far and hope that a new sealing
      cement with more reduced hardening times will soon be available.

PMID- 16575385
TI  - The prosthetically guided osteodistraction of the mandible in the microvascular
      bone reconstruction after cancer surgery.
AB  - The rehabilitation of the mandible after ablation cancer surgery is a challenge.
      Furthermore, osteodistraction in the microvascular fibula flap makes it difficult
      to predict adequate bone lengthening. The aim of this article is to evaluate a
      protocol used to manufacture templates for measuring osteodistraction, in terms
      of force vectors and definitive height. An accurate prosthetic wax-up with guide
      pins measuring the quantity of bone lengthening must be performed to manufacture
      the template. This device may be used to establish the end of the osteo
      distraction in respect to the vertical dimension of the definitive occlusion.

PMID- 16575386
TI  - Traumas of the middle skull base with TMJ involvement. Case report.
AB  - The authors report their experience with temporomandibular joint (TMJ) traumas
      involving breakage of the roof of the glenoid cavity, an infrequent event that
      occurs in those cases in which, as a result of the condylar neck not fracturing,
      the traumatic energy is transmitted to the middle skull base. As the literature
      contains no valid series for establishing standardized protocols for the
      treatment of these fractures, we propose our own orthopedic-functional approach.
      The patient observed by us had suffered a cranio-facial trauma and presented the
      classical symptoms and signs of TMJ traumas and complete bilateral Bell
      paralysis. He was subjected to a CAT scan and then to 2-stage treatment
      consisting of functional rest with liquid diet followed by physiotherapy. An
      almost total recovery in TMJ function was observed after 1 month. At 1-year
      follow-up the facial paralysis had resolved completely. On the basis of our
      experience, breakages of the glenoid cavity can be compared, in terms of
      treatment procedure, to intracapsular fractures of the TMJ with surgery confined
      to cases of ankylosis sequelae. To avoid the onset of ankylosis careful control
      of clinical, functional and radiological follow-up is required.

PMID- 16575387
TI  - 13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1
      sebocytes.
AB  - Isotretinoin (13-cis retinoic acid (13-cis RA)) is the most potent inhibitor of
      sebum production, a key component in the pathophysiology of acne, yet its
      mechanism of action remains largely unknown. The effects of 13-cis RA, 9-cis
      retinoic acid (9-cis RA), and all-trans retinoic acid (ATRA) on cell
      proliferation, apoptosis, and cell cycle proteins were examined in SEB-1
      sebocytes and keratinocytes. 13-cis RA causes significant dose-dependent and time
      dependent decreases in viable SEB-1 sebocytes. A portion of this decrease can be
      attributed to cell cycle arrest as evidenced by decreased DNA synthesis,
      increased p21 protein expression, and decreased cyclin D1. Although not
      previously demonstrated in sebocytes, we report that 13-cis RA induces apoptosis
      in SEB-1 sebocytes as shown by increased Annexin V-FITC staining, increased TUNEL
      staining, and increased cleaved caspase 3 protein. Furthermore, the ability of 13
      cis RA to induce apoptosis cannot be recapitulated by 9-cis RA or ATRA, and it is
      not inhibited by the presence of a retinoid acid receptor (RAR) pan-antagonist
      AGN 193109. Taken together these data indicate that 13-cis RA causes cell cycle
      arrest and induces apoptosis in SEB-1 sebocytes by a RAR-independent mechanism,
      which contributes to its sebosuppressive effect and the resolution of acne.

PMID- 16575388
TI  - The small antitumoral immune response modifier imiquimod interacts with adenosine
      receptor signaling in a TLR7- and TLR8-independent fashion.
AB  - Imiquimod, a small-molecule immune response modifier of the imidazoquinoline
      family, has shown profound antitumoral and antiviral efficacy both in vitro and
      in clinical applications in vivo. It has been demonstrated that this activity is
      mediated through the Toll-like receptor (TLR)7- and TLR8-signaling cascade
      resulting in the secretion of proinflammatory cytokines and, consecutively,
      induction of a tumor-directed cellular immune response. In addition, imiquimod
      exerts a direct proapoptotic activity in tumor cells. We demonstrate here that
      imiquimod induces activation of the transcription factor NF-kappaB and the
      downstream production of proinflammatory cytokines in the absence of TLR7 and
      TLR8. In Chinese hamster ovary cells stably transfected with the human adenosine
      receptor subtypes, we then show in radioligand-binding competition experiments
      that imiquimod binds to adenosine receptors at concentrations relevant in
      clinical settings, with highest affinities to the A(1) and A(2A) subtypes. The
      effect on the receptor-mediated activation of adenylyl cyclase was also studied,
      and these experiments revealed that imiquimod acts as an adenosine receptor
      antagonist. In addition, imiquimod had an inhibitory effect on adenylyl cyclase
      activity downstream from the receptor. Finally, using transformed human
      keratinocytes, we provide experimental evidence that imiquimod and A(2A)
      adenosine receptor-specific compounds similarly induce proinflammatory cytokines
      in the absence of immune cells. Thus, imiquimod appears to suppress an important
      feedback mechanism of inflammation by antagonism of adenosine receptor-dependent
      increase of cAMP and a concomitant receptor-independent inhibition of cAMP
      production. These novel mechanisms presumably act synergistic with the positive
      induction of proinflammatory cytokines and can, at least in part, explain the
      profound inflammation observed in some patients in vivo.

PMID- 16575389
TI  - Insulin-like growth factor-1 induces lipid production in human SEB-1 sebocytes
      via sterol response element-binding protein-1.
AB  - An understanding of the molecular signaling involved in sebaceous gland lipid
      production is needed to develop therapeutic targets to improve acne. Treatment
      with methylisobutylxanthine, dexamethasone, and a high dose of insulin (MDI) has
      been shown to differentiate 3T3-L1 preadipocytes into adipocytes, a
      differentiation marked by an increase in lipid production. The present study has
      the following aims: (1) Since high doses of insulin, as found in MDI, will
      activate the IGF-1 receptor, we sought to determine if IGF-1 is capable of
      reproducing the lipogenic effect seen with MDI treatment, and (2) to determine if
      the sterol response element-binding protein-1 (SREBP-1) pathway mediates the
      increase in lipogenesis. Here we report that MDI increases lipogenesis and that
      this effect can be attributed wholly to the high-dose insulin in SEB-1 cells.
      Further, we show that a physiologically relevant dose of IGF-1 or high-dose (1
      microM) insulin induces an increase in SREBP-1 mRNA, protein, and total lipid
      production; while 100 nM insulin induces lipogenesis yet the SREBP protein levels
      remain unchanged. These data indicate that activation of the IGF-1 receptor
      increases lipogenesis in SEB-1 cells through both SREBP-dependent and SREBP
      independent pathways.

PMID- 16575390
TI  - Cutaneous endothelial cell activation in normal skin of patients with dermatitis
      herpetiformis associated with increased serum levels of IL-8, sE-Selectin, and
      TNF-alpha.
AB  - The mechanisms that lead to the development of skin lesions in patients with
      dermatitis herpetiformis (DH) are not known. We hypothesized that an ongoing
      immune response in the gut of patients with DH would result in an increase in
      circulating cytokines and be associated with endothelial cell activation,
      creating a proinflammatory environment in the skin. Skin biopsies from the normal
      appearing inner arm of 11 DH patients, with no active skin lesions, and 12 normal
      subjects were analyzed for E-selectin (E-sel) and ICAM-1 mRNA. DH patients' skin
      expressed markedly increased levels of E-sel mRNA. Mean E-sel mRNA expression in
      DH skin was 1,271 (range 63.78-5861) times greater than that of a control, normal
      skin (P<0.001) with no significant increased expression of ICAM-1 mRNA. Serum
      levels of soluble E-selectin (sE-sel), IgA anti-tissue transglutaminase
      antibodies, and serum IL-8 levels were significantly increased in patients with
      DH. These studies demonstrate that patients with DH have evidence of endothelial
      cell activation in the skin and systemic manifestations of the ongoing
      inflammation associated with the mucosal immune response. Endothelial cell
      activation may play a critical role in the development of skin lesions in
      patients with DH and may represent a common mechanism for cutaneous
      manifestations of inflammatory gastrointestinal diseases.

PMID- 16575391
TI  - Dexamethasone induction of keloid regression through effective suppression of
      VEGF expression and keloid fibroblast proliferation.
AB  - The biological mechanism underlying steroid therapy for treating keloids remains
      unclear. Analytical results demonstrated that topical intra-lesional steroid
      injections suppress vascular endothelial growth factor (VEGF) expression in
      keloid tissue and induce its regression in vivo. This study investigated whether
      glucocorticoid (dexamethasone) downregulates VEGF expression and hinders keloid
      fibroblast (KF) proliferation in keloid regression. Primary KF cultures were
      treated with various concentrations of dexamethasone, glucocorticoid receptor
      (GR) antagonist (mifeprostone, RU-486), VEGF-A antibody, VEGF receptor-2 (VEGF
      R2) antagonist (SU-5416), and VEGF protein. Analytical results demonstrated that
      dexamethasone retarded KFs proliferation. However, suppression of fibroblast
      proliferation by dexamethasone pre-treatment was reduced by adding exogenous VEGF
      protein. Dexamethasone suppressed endogenous VEGF mRNA induction, protein
      expressed by KFs, and angiogenesis activity detected by a tube-forming assay of
      human umbilical vein endothelial cells co-cultured fibroblasts. These effects
      were reversed by pre-treatment with RU-486, and not by pre-treatment with SU
      5416. Thus, dexamethasone induces keloid regression via interaction with the GR
      and suppresses endogenous VEGF expression and fibroblast proliferation. However,
      exogenous VEGF promotes fibroblast proliferation through the GR-independent
      pathway. Modulation of VEGF production may comprise a valuable treatment modality
      for keloids.

PMID- 16575392
TI  - A gene locus responsible for reticulate pigmented anomaly of the flexures maps to
      chromosome 17p13.3.
AB  - Reticulate pigmented anomaly of the flexures (RPAF), also called Dowling-Degos
      disease, is a rare autosomal-dominant cutaneous disorder characterized by spotted
      and reticulate pigmentation of the flexures. The gene, or even the chromosomal
      location, for RPAF has not yet been identified. In this study, one Chinese family
      with RPAF was identified and subjected to a genomewide screen for linkage
      analysis. We identified a locus at chromosome 17p13.3 with a maximum two-point
      limit of detection score of 3.61 at markers D17S831and D17S1866 (at recombination
      fraction theta=0.00). Haplotype analyses indicated that the disease gene is
      located within the 6.8 cM region distal to D17S1798. It is the first locus
      identified for RPAF. This study provides a map location for isolation of a
      disease gene causing RPAF.

PMID- 16575393
TI  - An autosomal recessive form of monilethrix is caused by mutations in DSG4:
      clinical overlap with localized autosomal recessive hypotrichosis.
AB  - Monilethrix is a structural defect of the hair shaft usually inherited in an
      autosomal dominant fashion and caused by mutations in the hHb1, hHb3, and hHb6
      keratin genes. Autosomal recessive inheritance in this disease has been
      sporadically reported. We encountered 12 Jewish families from Iraq, Iran, and
      Morocco with microscopic findings of monilethrix, but with no evidence of
      vertical transmission. Since no mutations were found in these three hair keratin
      genes, we examined nine chromosomal regions containing gene clusters encoding
      skin and hair genes. On chromosome 18q, a common haplotype in the homozygous
      state was found among all seven Iraqi patients, but not in 20 controls
      (P<0.0001). Sequencing of the main candidate gene from this region revealed four
      different mutations in desmoglein 4 (DSG4). Mutations in DSG4 have been
      previously reported in localized autosomal recessive hypotrichosis, a disorder
      that shares the clinical features of monilethrix but lacks the characteristic
      microscopic appearance of the hair shaft. Our findings have important
      implications for genetic counseling to monilethrix patients and families, and
      suggest that DSG4-associated hair disorders may be more common than previously
      thought.

PMID- 16575394
TI  - Rottlerin, a specific inhibitor of protein kinase C-delta, impedes barrier repair
      response by increasing intracellular free calcium.
AB  - Several signals have been suggested in maintaining skin barrier homeostasis, but
      epidermal calcium ions are currently thought to be a main signaling factor. It is
      not clear, however, exactly how an intracellular calcium level decreases in
      response to the loss of an extracellular calcium gradient. In this study, we
      investigated the effects of several broad-type and isozyme-specific protein
      kinase C (PKC) inhibitors on epidermal permeability barrier recovery. Topical
      application of chelerythrine chloride, a broad-type PKC inhibitor, and rottlerin,
      a PKCdelta-specific inhibitor, significantly impeded the barrier recovery rate at
      3 and 6 hours after barrier disruption. A significant decrease in the number and
      secretion of lamellar bodies was also observed at the inhibitor-treated site.
      Calcium ion-capture cytochemistry showed that the epidermal calcium gradient was
      rapidly reformed in inhibitor-treated skin, though recovery of the corresponding
      barrier function was not observed. In cultured keratinocytes treated with either
      inhibitor, increased intracellular calcium did not return to the baseline
      concentration after extracellular calcium decreased. These results suggest that
      PKC inhibitors, especially a PKCdelta-specific inhibitor, delay barrier recovery
      by affecting the intracellular calcium concentration after a loss of the
      extracellular calcium gradient. Furthermore, PKCdelta is important in controlling
      a decrease in intracellular calcium concentration.

PMID- 16575395
TI  - Impact of psoriasis on health-related quality of life decreases over time: an 11
      year prospective study.
AB  - Although psoriasis typically affects patients for many years, studies quantifying
      impairment in health-related quality of life (HRQOL) owing to psoriasis over long
      periods are lacking. This study, which interviewed patients independent of
      psoriasis care, investigates change in the impact of psoriasis on HRQOL over 11
      years and factors associated with change among 484 patients using the Impact of
      Psoriasis Questionnaire (IPSO). We determined changes in the impact of psoriasis
      on HRQOL using a psychometrically optimized version of the IPSO. In 1993, the
      patients were 53+/-11.4 years and 61.8% males. From 1993 to 2004, impact on most
      social aspects of HRQOL remained stable, but concerns related to physical
      appearance decreased (e.g., 36-13%, P = 0.001). Over 11 years, the proportion of
      patients with low overall impact of psoriasis increased significantly (43-53%, P
      < 0.001). Mean IPSO scores (range 0-22) decreased by one-fifth (5-4, P < 0.001).
      At follow-up, patients reporting poor health had mean improvement in HRQOL about
      three times greater than those in good health (P < 0.05). In this large cohort
      interviewed independent of treatments and psoriasis status, impact of psoriasis
      on HRQOL decreases over time. For chronic diseases, HRQOL is best measured over
      time and independently of seeking treatment.

PMID- 16575396
TI  - Frequent [corrected] hyperphosphorylation of ribosomal protein S6 [corrected] in
      lymphangioleiomyomatosis-associated angiomyolipomas.
AB  - Lymphangioleiomyomatosis is a progressive lung disease characterized by a diffuse
      proliferation of pulmonary smooth muscle cells and cystic degeneration.
      Lymphangioleiomyomatosis can occur either independently of other disease or in
      association with tuberous sclerosis complex, a tumor-suppressor gene syndrome
      caused by mutations that inactivate either TSC1 or TSC2. TSC2 mutations and loss
      of heterozygosity have been identified in sporadic lymphangioleiomyomatosis
      associated angiomyolipomas, thus implicating the TSC/Ras homolog-enriched in
      brain (Rheb)/mammalian target of Rapamycin (mTOR)/p70 S6 kinase signaling pathway
      in their pathogenesis. This study was undertaken to determine whether the
      mTOR/p70 S6 kinase signaling pathway is activated in lymphangioleiomyomatosis
      associated angiomyolipomas lacking TSC1/TSC2 loss of heterozygosity. Phospho
      ribosomal protein S6 (Ser235/236) immunohistochemistry was performed on five
      lymphangioleiomyomatosis-associated angiomyolipomas, two matched
      lymphangioleiomyomatosis pulmonary samples, and three sporadic angiomyolipomas.
      TSC1/TSC2 loss of heterozygosity was previously excluded in these
      angiomyolipomas. Moderate or strong phospho-ribosomal protein S6 immunoreactivity
      was found in all lymphangioleiomyomatosis-associated and sporadic
      angiomyolipomas, suggesting a high incidence of mTOR/p70 S6 kinase signaling
      pathway activation despite a lack of TSC1/TSC2 loss of heterozygosity. Focally
      positive phospho-S6 staining was also evident in both lymphangioleiomyomatosis
      pulmonary samples. We hypothesized that this S6 hyperphosphorylation could
      reflect mutational activation of Rheb or Rheb-like protein (RhebL1), Ras family
      members which directly activate mTOR. Mutational analysis performed on DNA from
      these eight angiomyolipomas plus five additional sporadic angiomyolipomas did not
      reveal mutations in exons 3 and 4 (homologous sites of Ras activating mutations)
      of either Rheb or RhebL1. These data suggest that activation of the Rheb/mTOR/p70
      S6 kinase pathway is related to the pathogenesis of lymphangioleiomyomatosis
      associated and sporadic angiomyolipomas lacking TSC1/TSC2 loss of heterozygosity.
      This high incidence of mTOR signaling pathway activation suggests that treatment
      with mTOR inhibitors, such as Rapamycin, may benefit patients with
      angiomyolipomas independent of the detection of TSC1/TSC2 loss of heterozygosity.

PMID- 16575397
TI  - The impact of pathologist experience on liver transplant biopsy interpretation.
AB  - We studied the impact of pathologist experience on liver transplant biopsy
      interpretation for cases designated 'nonspecific' by pathologists at a
      nontransplant center. Among 102 consecutive liver transplant biopsies from 92
      patients performed at the Foothills Medical Center, 30 liver biopsies from 23
      patients were designated 'nonspecific' by the local pathologist. These biopsy
      slides were independently reviewed by an expert in liver transplant pathology at
      a major US transplant center. The expert pathologist was given only the
      information on the original requisition. In seven biopsies from five patients,
      there was full agreement between the external expert and the local pathologist.
      In 10 biopsies from six patients, the expert concurred with the initial
      assessment but emphasized critical negatives such as 'no evidence of rejection or
      recurrent hepatitis'. A discrepant diagnosis was found in 13 biopsies from 12
      patients. In five biopsies from four patients, the revised diagnoses were
      inaccurate due to insufficient or misleading clinical information on the
      requisition. In eight biopsies from eight patients, the revised diagnoses were
      proven to be correct by clinicopathologic correlation. Our study shows that
      pathology expertise helped to clarify the diagnosis in about 27% of cases, which
      justifies the cost of obtaining a second opinion in difficult biopsies.
      Misinterpretation by the expert pathologist in up to 17% of biopsies highlights
      the importance of direct communication between hepatologist and pathologist in
      order to achieve a correct diagnosis. Familiarity with those cases with
      relatively uncommon histology, a diligent search for subtle morphologic changes,
      and use of standard terminology could improve the quality of liver transplant
      biopsy interpretation in a nontransplant center.

PMID- 16575398
TI  - Acquired cystic disease-associated renal tumors: an immunohistochemical and
      fluorescence in situ hybridization study.
AB  - End-stage renal disease is associated with an increased incidence of renal cell
      neoplasms. Among these, recent studies have identified tumors with unusual
      histological patterns that do not fit into the categories recognized in the
      current classification system. These tumors often occur in kidneys with acquired
      cystic disease and are composed mainly of large eosinophilic cells arranged in
      solid, cribriform, acinar, or papillary patterns. They also contain deposits of
      calcium oxalate crystals. We investigated three eosinophilic epithelial tumors
      arising in kidneys with acquired cystic disease from three patients. Each of the
      tumors was composed of large eosinophilic cells arranged in solid, acinar, or
      tubulocystic architecture. Deposits of calcium oxalate crystals were present in
      each tumor. Hale's colloidal stain showed a positive cytoplasmic reaction in one
      of the neoplasms. Immunohistochemistry displayed positive results for CD10 (3/3),
      AE1/AE3 (3/3), alpha-methylacyl-CoA racemase (2/3), CAM5.2 (2/3), and vimentin
      (1/3). Reactions for epithelial membrane antigen, cytokeratin 7, and high
      molecular weight cytokeratin (34betaE12) were negative. Fluorescence in situ
      hybridization analysis showed no losses or gains of chromosomes 1, 2, 6, 10, or
      17 in one tumor. There were gains of chromosomes 1, 2, and 6 in two tumors. One
      of these tumors also showed gains of chromosome 10. Eosinophilic renal cell
      tumors associated with acquired cystic disease have immunophenotypes and genetic
      profiles distinct from the renal cell neoplasms recognized in the current
      classification of renal cell neoplasia, and should be considered as a distinct
      clinicopathologic entity in the spectrum of renal cell neoplasia.

PMID- 16575399
TI  - Id proteins expression in prostate cancer: high-level expression of Id-4 in
      primary prostate cancer is associated with development of metastases.
AB  - A major cause of treatment failure for prostate cancer is the development of
      androgen-independent metastatic disease. Id protein family, a group of basic
      helix-loop-helix transcription factors, has been shown to be involved in
      carcinogenesis and a prognostic marker in several types of human cancers. In this
      study, we examined the expressions of four Id proteins, Id-1, -2, -3 and -4, in
      125 clinical prostate cancer specimens as well as 40 nodular hyperplasia
      specimens by immunohistochemistry. The expressions of Id proteins were correlated
      with Gleason grading and metastatic progress of the tumors. We found that Id
      proteins were dysregulated in prostate cancer. Id-1 and -2 expressions were
      elevated while Id-3 and -4 expressions were reduced in prostate cancers compared
      to nodular hyperplasia. Cytoplasmic staining of Id-1 (P=0.013) and nuclear
      staining of Id-2 (P=0.001) and Id-4 (P<0.001) were positively correlated with
      Gleason score. The results indicate that these Id proteins may play a positive
      role in the development of prostate cancer. In contrast, Id-3 might have an
      inverse relationship with prostate neoplastic transformation (P=0.002) and cancer
      progression (P=0.022). We found that Id-4 nuclear overexpression in the primary
      prostate cancers significantly increased the risks to the development of
      metastasis in the patients (odds ratio=3.215, 95% confidence interval=1.150
      8.987, P=0.026). Our results suggest that in prostate cancer patients,
      differential Id proteins expressions may be a useful marker for poor prognosis,
      and Id-4 may be a potential prognostic marker for distant metastasis.

PMID- 16575400
TI  - Cell death, proliferation and repair in human myocarditis responding to
      immunosuppressive therapy.
AB  - In this study, we evaluate cell death, proliferation and repair in left
      ventricular endomyocardial biopsies from 20 patients with active lymphocytic
      myocarditis worsening or recovering from cardiac dysfunction after 6-months
      immunosuppression. Apoptosis and necrosis were assessed by in situ ligation of
      hairpin probes, proliferation by Ki67 and MCM5 labelling of myocytes, repair by
      electron microscopy, morphometric study of percent myofibrillar area and real
      time polymerase chain reaction of alpha-and beta-Myosin Heavy Chain (MHC).
      Apoptosis and necrosis decreased in post- vs pretreatment biopsies by 85 and 62%,
      respectively in responders, while increased by 42 and 46% in nonresponders. Ki67
      and MCM5-positive myocytes were higher vs controls at baseline and increased by
      43 and 38% at follow-up in responders and by 75 and 63% in nonresponders.
      Myofibrillar area reduced in pretreatment samples, increased by 33% at follow-up
      in responders, correlated with percent enhancement of ejection fraction and was
      associated with increased alpha-MHC expression and alpha/beta-MHC ratio. In
      follow-up biopsies of nonresponders, myofibrillar area diminished by 36% and
      correlated with percent decrease of ejection fraction. Our results suggest that
      recovery of cardiac function in myocarditis responding to immunosuppression is
      associated with inhibition of cell death, activation of cell proliferation and
      with newly synthesized contractile material.

PMID- 16575401
TI  - Comprehensive analysis of 19q12 amplicon in human gastric cancers.
AB  - Amplification at 19q12 has been observed in multiple tumor types, while cyclin E1
      (CCNE1) has been considered to be the key oncogene within this amplicon. We have
      previously applied cDNA microarray analysis to systematically characterize gene
      expression patterns of gastric tumor and nontumor samples. We identified a
      cluster of five tightly coregulated genes all located at chromosome 19q12,
      including CCNE1. We found that the 19q12 gene cluster is highly expressed in
      gastric tumors compared to nontumor gastric samples. Array based comparative
      genomic hybridization and real-time PCR was used to define the boundary of the
      19q12 amplicon to a region of approximately 200 kb. Interestingly, we found that
      in some cases amplification at 19q12 was not associated with DNA copy number gain
      at CCNE1, suggesting that some other genes within the 19q12 amplicon may also
      have important function during gastric tumorigenesis. We found high expression of
      the 19q12 gene cluster to be statistically correlated with the cell proliferation
      gene signature. Using the SAM software, we identified a set of 577 genes whose
      expression levels positively correlated with the 19q12 gene cluster. GO term
      analysis revealed that this genelist is enriched with genes involved in cell
      cycle regulation and cell proliferation. In conclusion, expression array analysis
      combined with array comparative genomic hybridization and real-time PCR provides
      a new and powerful tool to identify clusters of genes which may be regulated by
      genomic DNA aberrations. In addition, our study indicates that amplification at
      19q12 is associated with cell proliferation in vivo.

PMID- 16575402
TI  - Cellular retinol binding protein-1 expression in endometrial hyperplasia and
      carcinoma: diagnostic and possible therapeutic implications.
AB  - Cellular retinol binding protein-1 (CRBP-1) contributes to the maintenance of the
      differentiative state of endometrial glandular cells through the regulation of
      bioavailability of retinol and derivatives, but its role in endometrial
      oncogenetic process remains unclear. Antibodies to CRBP-1, estrogen and
      progesterone receptors (ER and PR) were applied to paraffin sections of
      proliferative (n = 10) and secretory endometrium (n = 9), and to endometrial
      polyps (n = 6), simple (n = 7), complex (n = 3) and atypical endometrial
      hyperplasias (n = 9) as well as to 47 endometrioid carcinomas of different
      histological grade (G) (G1, n = 18; G2, n = 19; G3, n = 10). Four serous and two
      clear cell carcinomas were also examined. In glandular cells, CRBP-1 positivity
      was mainly cytoplasmic and rarely in the nuclei. CRBP-1 immunodetection was
      weakly positive in proliferative and low and focal in secretory endometrium and
      higher in atypical as compared to simple and complex hyperplasias. CRBP-1
      expression in G1 endometrioid carcinomas was similar to that in atypical
      hyperplasias. In the latter, the highest CRBP-1 expression was observed in areas
      of squamous differentiation. Semiquantitative evaluation revealed a significant
      decrease of cytoplasmic CRBP-1 immunoreactivity with the increase of tumor grade.
      Among G3 endometrioid carcinomas, 60% were CRBP-1 negative, whereas the remaining
      cases showed a very low and focal positivity. Serous carcinomas were also CRBP-1
      negative. When areas of different grading were present within the same tumor,
      less differentiated areas retained a lower CRBP-1 immunoreaction. The progressive
      decrease of CRBP-1 paralleled that of ER and PR immunodetection. RT-PCR in eight
      endometrioid carcinomas suggested a decrease of CRBP-1 with the increase of tumor
      grade also at transcriptional level. Our results indicate that CRBP-1
      immunodetection may constitute an additional tool for histological grading of
      endometrial carcinoma. The CRBP-1 loss during the progression of endometrial
      cancer suggests a new potential target for pharmacological strategies aimed to
      counteract its progression by increased intracellular retinol bioavailability.

PMID- 16575403
TI  - Potential crosstalk between insulin-like growth factor receptor type 1 and
      epidermal growth factor receptor in progression and metastasis of pancreatic
      cancer.
AB  - The insulin-like growth factor receptor type 1 (IGF1R) and epidermal growth
      factor receptor (EGFR) are reportedly overexpressed in pancreatic cancer.
      However, the correlation between activated EGFR and IGF1R and their
      clinicopathological implications still remain unclear. The cellular localization
      and overexpression of IGF1R and EGFR were investigated immunohistochemically in
      primary invasive ductal pancreatic carcinomas obtained from 74 patients who
      underwent radical surgical resection. We also compared the status of IGF1R and
      EGFR overexpression between primary tumors and hepatic metastatic tumors obtained
      from 44 autopsied patients. Among the 74 surgically resected primary tumors,
      cytoplasm- and membrane-dominant EGFR overexpression was detected in 22 (30%) and
      7 (9%), respectively, whereas cytoplasm- and membrane-dominant IGF1R
      overexpression was detected in 8 (11%) and 28 (38%), respectively. Membrane
      dominant EGFR and cytoplasm-dominant IGF1R were more frequent in lower-grade
      tumors and correlated with favorable prognosis, whereas cytoplasm-dominant EGFR
      and membrane-dominant IGF1R were more frequent in higher-grade tumors and
      correlated with poor prognosis. In 36 autopsy specimens of pancreatic tumor with
      concurrent overexpression of IGF1R and EGFR, there was an inverse correlation
      between the IGF1R and EGFR localization patterns (P = 0.001). In the hepatic
      metastatic tumors obtained by autopsy, the incidences of both IGF1R and EGFR
      overexpression were much higher than in the surgically resected primary tumors.
      More than half of the autopsy cases consistently showed membrane-dominant EGFR
      expression in both the primary tumor and hepatic metastases, whereas IGF1R
      expression showed considerable variation. Crosstalk between differently localized
      IGF1R and EGFR might play a role in determining the biological aggressiveness of
      pancreatic cancer, although their cellular localization may often alter during
      the process of metastasis.

PMID- 16575404
TI  - Some p53-binding proteins that can function as arbiters of life and death.
AB  - Four sets of p53-binding proteins are discussed in this review. These are the E2F
      family, the ASPP family, Y-box-binding protein YB1, and the prolyl isomerase
      Pin1. Each appears to play a role in the decision by p53 to induce an arrest of
      cell proliferation or apoptosis and they may also be independent markers of
      cancer. Their activities appear to be linked with the cell cycle and they may
      also interact with each other. In this review, the properties of each protein
      class are discussed as well as how they affect p53 functions. A model is proposed
      as to how their activities might be coordinated.

PMID- 16575405
TI  - Transcriptional regulation by p53: one protein, many possibilities.
AB  - The p53 tumor suppressor protein is a DNA sequence-specific transcriptional
      regulator that, in response to various forms of cellular stress, controls the
      expression of numerous genes involved in cellular outcomes including among
      others, cell cycle arrest and cell death. Two key features of the p53 protein are
      required for its transcriptional activities: its ability to recognize and bind
      specific DNA sequences and to recruit both general and specialized
      transcriptional co-regulators. In fact, multiple interactions with co-activators
      and co-repressors as well as with the components of the general transcriptional
      machinery allow p53 to either promote or inhibit transcription of different
      target genes. This review focuses on some of the salient features of the
      interactions of p53 with DNA and with factors that regulate transcription. We
      discuss as well the complexities of the functional domains of p53 with respect to
      these interactions.

PMID- 16575406
TI  - Mouse bites dogma: how mouse models are changing our views of how P53 is
      regulated in vivo.
AB  - P53 is a transcription factor that can cause cells to be eliminated by apoptosis
      or senescent-like arrest upon its activation by irreparable genetic damage,
      excessively expressed oncogenes, or a broad spectrum of other stresses. As P53
      executes life and death decisions, its activity must be stringently regulated,
      which implies that it is not likely to be controlled by a simple regulatory
      mechanism involving a binary on-off switch. This brief review will summarize a
      subset of the new information presented at the 10th P53 workshop in Dunedin, New
      Zealand in November 2004 as well as very recent publications that provide new
      insights into the molecular regulators of P53. Data emerging from mouse models
      provide a fundamentally different view of how P53 is regulated than suggested by
      more traditional in vitro approaches. The differences between cell culture and
      mouse models demonstrate the importance of preserving stoichiometric
      relationships between P53 and its various regulators to obtain an accurate view
      of the relevant molecular mechanisms that control P53 activity.

PMID- 16575407
TI  - Activation of Ras/Raf protects cells from melanoma differentiation-associated
      gene-5-induced apoptosis.
AB  - Melanoma differentiation-associated gene-5 (mda-5) was the first molecule
      identified in nature whose encoded protein embodied the unique structural
      combination of an N-terminal caspase recruitment domain and a C-terminal DExD/H
      RNA helicase domain. As suggested by its structure, cumulative evidences
      documented that ectopic expression of mda-5 leads to growth inhibition and/or
      apoptosis in various cell lines. However, the signaling pathways involved in mda
      5-mediated killing have not been elucidated. In this study, we utilized either
      genetically modified cloned rat embryo fibroblast cells overexpressing different
      functionally and structurally distinct oncogenes or human pancreatic and
      colorectal carcinoma cells containing mutant active ras to resolve the role of
      the Ras/Raf signaling pathway in mda-5-mediated growth inhibition/apoptosis
      induction. Rodent and human tumor cells containing constitutively activated
      Raf/Raf/MEK/ERK pathways were resistant to mda-5-induced killing and this
      protection was antagonized by intervening in this signal transduction cascade
      either by directly inhibiting ras activity using an antisense strategy or by
      targeting ras-downstream factors, such as MEK1/2, with the pharmacological
      inhibitor PD98059. The present findings provide a further example of potential
      cross-talk between growth-inhibitory and growth-promoting pathways in which the
      ultimate balance of these factors defines cellular homeostasis, leading to
      survival or induction of programmed cell death.

PMID- 16575409
TI  - The relation of volume and outcome in trabeculectomy.
AB  - BACKGROUND/AIMS: Higher case volume has been associated with improved outcomes
      for a number of procedures. This study was designed to investigate whether this
      relationship existed for trabeculectomy. METHODS: The study was retrospective and
      conducted at an ophthalmic unit in the UK. All patients who had unenhanced
      trabeculectomy between 1996 and 2000 were identified. From their notes, the
      surgeon who performed the trabeculectomy was ascertained as were any unplanned
      interventions (eg conjunctival suturing, anterior chamber reformation, repeated
      attendances) within the first month of surgery. RESULTS: Two hundred and eleven
      trabeculectomies were performed over the study period. Twenty nine had unplanned
      interventions within the first postoperative month. Analysis of the data
      indicated that surgeons who performed less than eight operations per year had
      more complications than those who performed more than 10 per annum. This
      difference was only significant (chi(2)=4.0, P=0.045) when the data were
      aggregated. When separated per year, although not significant, the complication
      rate of the lower volume group was always higher than the group performing more
      than 10 per year. CONCLUSIONS: The results suggest that trabeculectomy can be
      added to the list of procedures in which larger case volume is associated with
      fewer early complications and potentially a better outcome. The findings, if
      replicated, tend to strengthen the argument for subspecialisation in glaucoma
      with its implications for training and revalidation.

PMID- 16575408
TI  - The estrogen-responsive B box protein: a novel enhancer of interleukin-1beta
      secretion.
AB  - The estrogen-responsive B box protein (EBBP) and Pyrin belong to a family of
      structurally related proteins. While mutations in the pyrin gene cause an
      autoinflammatory disease, the biological function of EBBP is unknown. In this
      study, we identified the proinflammatory cytokine interleukin-1beta (IL-1beta) as
      an EBBP-binding partner. Furthermore, caspase-1 and NACHT, LRR and Pyrin domain
      containing protein (NALP) 1, two components of the recently identified
      inflammasome, a platform for the activation of caspase-1, also interact with
      EBBP. These proteins bind to the RFP domain of EBBP, suggesting that this domain
      of so far unknown function is an important protein-binding domain. EBBP was
      secreted in a caspase-1-dependent manner from cultured cells, and its secretion
      was enhanced by IL-1beta. Vice versa, endogenous and overerexpressed EBBP
      increased IL-1beta secretion. These results provide evidence for a role of EBBP
      in innate immunity by enhancing the alternative secretion pathway of IL-1beta.

PMID- 16575410
TI  - Macular hole surgery without prone positioning.
AB  - PURPOSE: To investigate the role of vitrectomy without prone posturing in the
      anatomic and functional outcome of macular hole surgery (MHS). METHODS: Forty-one
      consecutive eyes of 41 patients with stage II-IV full-thickness macular holes
      underwent pars plana vitrectomy and 16% C3F8 tamponade. In 25 cases posturing
      group (P), subjects were instructed to assume prone positioning for 10 days
      postoperatively, whereas in 16 cases non-posturing group (NP) patients were
      advised to avoid lying supine but no other posturing instructions were given.
      Preoperative, intraoperative and postoperative clinical data were collected, with
      macular hole closure rate and change in LogMAR visual acuity, contrast
      sensitivity, metamorphopsia, and 25-Visual Function Questionnaire (VFQ-25) being
      the primary outcome measures. RESULTS: Over a mean follow-up of 4.21.2 months,
      anatomical hole closure was noted in 22/25 (88%) and 14/16 (87.5%) in groups P
      and NP respectively. Visual acuity improved by a mean of eight letters and there
      was no significant difference in the two groups (P=0.724). Similarly,
      postoperative prone posturing did not have an effect on the final contrast
      sensitivity, metamorphopsia, and VFQ-25 composite scores (P=0.238, P=0.472, and
      P=0.87, respectively). However, eyes in group NP developed significantly more
      severe cataract in the early postoperative period (P=0.02). CONCLUSIONS: Prone
      posturing following MHS provides no functional or anatomic benefit but it is
      associated with slower progression of cataract. Combined phacovitrectomy without
      face down positioning may be considered for all phakic patients undergoing MHS.

PMID- 16575411
TI  - Cataract surgery for junior ophthalmologists: are there enough cases?
AB  - AIM: To evaluate those cases that are suitable for operation by the junior
      ophthalmic trainee. METHODS: A prospective survey of 96 consecutive cases from
      five consultant lists for phacoemulsification over a 1 month period were
      preoperatively assessed for their suitability for the ophthalmic trainee using
      set criteria. A checklist was designed for all patients and criteria were marked
      with reference to suitability by a single examiner. The criteria chosen were
      arbitrary and had no bearing on a consultant's final decision to allow the junior
      to operate. RESULTS: Twenty-two out of 96 cases (22.9%) were deemed to be
      suitable for operation by a junior ophthalmologist (ie 4.4 cases per consultant
      list). The three main reasons for exclusion were first eye case, eye for
      operation with visual acuity 6/12 or better, and mature cataract. DISCUSSION:
      Using our results, if 4.4 cases were suitable for a junior ophthalmologist per
      month, this would allow for adequate exposure during the early stages of
      training. However, if the number of relatively straightforward cases on training
      lists were to be reduced owing to unavailability on hospital waiting lists, this
      could potentially compromise ophthalmic training in the future.

PMID- 16575412
TI  - An unusual late complication of orbital floor fracture repair.

PMID- 16575413
TI  - A method for true endothelial cell (Tencell) transplantation using a custom-made
      cannula for the treatment of endothelial cell failure.
AB  - AIM: To describe a novel technique, true endothelial cell (Tencell) transplant,
      for the transfer of donor endothelial cells with only a Descemet's carrier in
      patients with endothelial cell failure. METHOD: Three patients treated for
      endothelial cell failure underwent Tencell transplantation. Two were performed to
      alleviate pain from bullous keratopathy, and one was performed to improve vision.
      Preoperative pain, vision, and corneal thickness were recorded and compared to
      the same parameters postoperatively. RESULTS: At 3 months postoperatively, all
      patients were pain free. The visual acuity had improved in all cases, and all
      three cases demonstrated a reduction of central corneal thickness. In two cases
      it was possible to perform an endothelial cell count. CONCLUSION: This is the
      first description of Tencell transplantation in living subjects.

PMID- 16575415
TI  - Identification of circulating malignant cells and its correlation with prognostic
      factors and treatment in uveal melanoma. A prospective longitudinal study.
AB  - PURPOSE: Most uveal melanoma patients (UMP) do not show evidence of metastases
      upon diagnosis. However, despite local tumour control, approximately 50% of them
      will develop metastases. These findings suggest that malignant cells may have
      already disseminated by the time of initial diagnosis. The purpose of the study
      was to detect circulating malignant cells (CMCs) in UMP and to correlate them
      with prognostic factors and therapy. METHODS: Nested reverse transcriptase
      polymerase chain reaction (RT-PCR) was used to detect CMCs. In each UMP, blood
      was collected every 3 months. In each visit, 20 RT-PCR tests were performed. The
      date of diagnosis, largest tumour dimension, type, and date of treatment were
      obtained. RESULTS: A total of 30 UMP were enrolled. Five patients were enrolled
      at the time of diagnosis and 25 patients between 1 and 17 years following
      diagnosis. No UMP showed clinical evidence of metastasis. A total of 136 visits
      were registered, 1360 samples collected, and 2720 RT-PCRs performed. CMCs were
      identified in 29 patients in 119 visits (87.5%). However, in each visit, a low
      number of positive tests were recorded. CMCs were found in newly diagnosed,
      irradiated, enucleated, and observed patients regardless of tumour size and time
      period following treatment. CONCLUSIONS: Uveal melanoma (UM) is not a localized
      ocular disease. CMCs were recorded at initial diagnosis confirming the early
      metastatic nature of UM. CMCs were present following treatment, including
      enucleation, demonstrating that CMCs are capable of disseminating and surviving,
      possibly as micrometastasis, which would contribute to the pool of CMCs at a
      later stage. Systemic therapy should be evaluated.

PMID- 16575414
TI  - Surgical outcome of primary developmental glaucoma: a single surgeon's long-term
      experience from a tertiary eye care centre in India.
AB  - PURPOSE: To determine the surgical outcome after initial surgery in children with
      primary developmental glaucoma (PDG). METHODS: Six hundred and twenty-four eyes
      of 360 consecutive patients who underwent primary combined trabeculotomy
      trabeculectomy (CTT) for PDG from January 1990 to June 2004 were studied. The
      main outcome measures were pre- and postoperative intraocular pressures (IOPs),
      corneal clarity, visual acuities, refractive errors, success rate, time of
      surgical failure, complications, and factors associated with poor outcome.
      RESULTS: IOP reduced from 28.1+/-7.5 to 14.9+/-5.9 mmHg (P<0.0001). Probability
      of success (IOP<21 mmHg) was 85.2, 80.4, 77.2, 72.6, 66.2, and 57.5% at first,
      second, third, fourth, fifth, and sixth years, respectively (Kaplan-Meier
      analysis). The mean follow-up period was 20.3+/-25.6 months (median, 6 months).
      Preoperatively, 243 eyes (67.5%) had significant corneal oedema. Postoperatively,
      normal corneal transparency was achieved in 162 eyes (46.0%). Data on Snellen
      visual acuity were available in 100 patients (27.8%). At the final follow-up
      visit, 42 patients (42.0%) had normal visual acuity (>or=20/60). Myopia (mean
      spherical equivalent, 6.1 D) was the most common (75.0%) refractive error. In
      multivariate analyses, failure increased by three-fold in the presence of
      preoperative IOP>35 mmHg (hazards ratio (HR)=3.12; 95% confidence interval (CI),
      1.4-6.7) and two-fold in cases with a history of prior glaucoma surgery (HR=2.57;
      95% CI, 1.1-6.0). There were no major intraoperative complications, bleb-related
      infection, or endophthalmitis. CONCLUSIONS: This series shows that prolonged IOP
      control can be achieved in patients with PDG and 42% of the patients gained
      normal visual acuity.

PMID- 16575416
TI  - Optic nerve changes in ocular toxoplasmosis.
AB  - PURPOSE: To determine the prevalence and features of the different types of
      involvement of the optic nerve in ocular toxoplasmosis. METHODS: Retrospective
      cross-sectional study. All patients with active ocular toxoplasmosis, consulting
      in the Uveitis Section of the Ophthalmology Department were selected. The
      involvement of the optic nerve was classified in the following categories:
      juxtapapillary retinochoroiditis, pure papillitis, neuroretinitis, distant
      lesion, and mixed lesion. RESULTS: The prevalence of involvement of the optic
      nerve found was 5.3%. The optic nerve involvement with the presence of a
      concurrent active distant lesion, occurred in 22 eyes (43.1%). A juxtapapillary
      lesion was found in 18 eyes (35.3%). Eight eyes (15.7%) presented lesions
      characterised as mixed. Isolated papillitis occurred in 3 eyes (5.9%). Forty
      seven lesions (95.9%) were unilateral and two (4.1%) were bilateral. Twenty-eight
      eyes (54.9%) had pre-existing lesions and 23 (45%) were primary lesions. Visual
      acuity improved in 35 eyes (71.4%) and remained unchanged in 14 eyes (28.5%).
      CONCLUSION: The involvement of the optic nerve most frequently found in ocular
      toxoplasmosis was optic nerve oedema with a concurrent distant active lesion. The
      second type of lesion most often found was juxtapapillary retinochoroiditis.
      Involvement was monocular in most cases and the visual prognosis was favourable.

PMID- 16575417
TI  - Goldmann applanation tonometer calibration error checks: current practice in the
      UK.
AB  - AIM: Assess current practice and views regarding checking Goldmann applanation
      tonometers for calibration errors in the United Kingdom. DESIGN: Questionnaire
      survey. METHODS: A total of 100 ophthalmology residents from England, Wales, and
      Scotland attending the 2004 Congress of the Royal College of Ophthalmologists,
      UK, responded to a structured questionnaire. They were asked the following: how
      often they used different tonometers between clinical sessions; how often they
      checked their tonometers for errors; and who they felt was responsible for
      checking tonometers for calibration errors. RESULTS: All respondents were using a
      different Goldmann tonometer for each clinic: 85% never check tonometers for
      errors; only 7% perform checks at the start of each clinical session; and 8%
      would only check the tonometer for calibration errors if they had suspicious or
      unexpected measurements. A total of 70% of respondents felt that calibration
      checks are not part of their responsibility. They believe that either nursing
      staff or other hospital staff should carry out calibration checks and ensure that
      tonometers are accurate. The remaining 30% felt that calibration checks should be
      carried out by the doctor using the tonometer. CONCLUSION: Despite evidence that
      Goldmann tonometers lose accuracy during routine use in clinical practice, only a
      minority are checking the tonometers for calibration errors. There is no
      consensus as to who should be responsible for ensuring that tonometer calibration
      is maintained. We recommend that tonometers should be checked for calibration
      errors at least on a monthly basis by individuals identified by departmental
      protocols.

PMID- 16575418
TI  - Bilateral foveal neurosensory detachment in hypertensive retinopathy demonstrated
      by optical coherence tomography.

PMID- 16575419
TI  - A case of cutaneous collision tumour: the importance of photographic
      documentation and large incisional biopsy.

PMID- 16575420
TI  - Maternal use of Loratadine during pregnancy and risk of hypospadias in offspring.
AB  - To examine the risk of hypospadias after exposure to loratadine and other
      antihistamines during pregnancy, we conducted a population-based case-control
      study in four Danish counties, which account for 30% of the Danish population
      (approximately 1.6 M). We obtained data on maternal use of antihistamines from
      prescription databases, and data on birth outcomes from the Danish Medical Birth
      Registry (MBR) and the Hospital Discharge Registry (HDR). A total of 65,383 male
      births with a full prescription history of the mother in the study period from
      1989-2002 were available for analysis. Within this cohort, we identified cases
      with a diagnosis of hypospadias, and 10 selected controls per case without such a
      diagnosis (matched on birth month, gender and year of birth). We identified 227
      cases of hypospadias recorded in the HDR within six months postpartum and 2270
      controls. One case (0.4%) and eight (0.4%) controls were exposed to loratadine in
      the first trimester and up to 30 days before the time of conception. The adjusted
      odds ratio (OR) for hypospadias among users of loratadine relative to non-users
      was 1.4 (95% CI: 0.2-11.2) and the corresponding OR for other antihistamines was
      1.9 (95% CI: 0.7-5.7). In this study, maternal exposure to loratadine did not
      appear to be associated with an increased risk of hypospadias when compared with
      other antihistamines, although it should be noted that the statistical precision
      of the risk estimates might be limited.

PMID- 16575421
TI  - Hb J- Meerut [alpha 120 (H3) Ala ->Glu (alpha1)] in a Turkish male.
AB  - Hb J Meerut is an infrequently found alpha-globin variant. It has previously been
      reported in various populations around the world. One particular case reported in
      1994 included a Turkish family. In this report, details of a second case of Hb J
      Meerut in a Turkish male who is unrelated to the first family are described. In
      the present case a slight increase in the oxygen affinity of Hb J Meerut,
      relative to that of the normal control, has been observed as detected by low p50
      values in arterial whole blood. Additionally, a slight increase in red blood cell
      count, as compared against a normal individual, was observed.

PMID- 16575422
TI  - Fewer classes of drugs for more and more psychiatric disorders.

PMID- 16575424
TI  - The "delayed onset" of antipsychotic action--an idea whose time has come and
      gone.
AB  - For years, it has been known that the "onset" of the antipsychotic response is
      "delayed," and this notion is expressed in many major textbooks, informs clinical
      decisions and has even led to the search for biological markers responsible for
      this delayed onset. But is the onset of antipsychotic action really delayed? In
      this review, we bring together data from several recent studies of antipsychotic
      drugs that show that the onset of the antipsychotic effect is within the first
      day; the effect is distinguishable from behavioural sedation; is specific to
      antipsychotic drugs; is seen with oral and parenteral preparations; and is seen
      with typical and atypical antipsychotics. More anti- "psychotic" improvement is
      seen within the first 2 weeks than in any other 2-week period thereafter, and
      more improvement is seen in the first month than in the rest of the year of
      follow-up. This body of data convincingly refutes the notion of "delay" in the
      onset of antipsychotic action and suggests an "early" onset instead. The
      implications of this finding for clinical decision-making, mechanisms of
      antipsychotic action and drug discovery are discussed.

PMID- 16575425
TI  - Increased positive emotional memory after repetitive transcranial magnetic
      stimulation over the orbitofrontal cortex.
AB  - OBJECTIVE: Several studies have demonstrated increased left orbitofrontal cortex
      (OFC) activity during negative and depressed mood. These mood states have also
      been associated with reduced memory for positive emotional stimuli. The aim of
      the present study was to investigate whether slow, inhibitory repetitive
      transcranial magnetic stimulation (rTMS) over the left OFC would improve memory
      for positive material. METHODS: We carried out a study with a double-blind,
      within-subjects design, in which 12 healthy volunteers received 20 minutes of
      slow rTMS over the left OFC, placebo treatment over the left OFC and rTMS over
      the left dorsolateral portion of the prefrontal cortex. Effects on memory for
      fearful and happy faces were investigated. RESULTS: Memory for happy faces was
      significantly improved after rTMS over the left OFC compared with placebo (t10 =
      2.4, p = 0.037). CONCLUSIONS: These findings suggest a role of the OFC in
      positive emotional memory, which is in accordance with neuroimaging and
      neuropsychological data. It may be argued that dense projections from the OFC to
      the limbic emotional circuit are involved in emotional memory and, therefore,
      play a role in the effects of rTMS that we observed.

PMID- 16575423
TI  - Antidepressant effects of exercise: evidence for an adult-neurogenesis
      hypothesis?
AB  - It has been hypothesized that a decrease in the synthesis of new neurons in the
      adult hippocampus might be linked to major depressive disorder (MDD). This
      hypothesis arose after it was discovered that antidepressant medications
      increased the synthesis of new neurons in the brain, and it was noted that the
      therapeutic effects of antidepressants occurred over a time span that
      approximates the time taken for the new neurons to become functional. Like
      antidepressants, exercise also increases the synthesis of new neurons in the
      adult brain: a 2-3-fold increase in hippocampal neurogenesis has been observed in
      rats with regular access to a running wheel when they are compared with control
      animals. We hypothesized, based on the adult-neurogenesis hypothesis of MDD, that
      exercise should alleviate the symptoms of MDD and that potential mechanisms
      should exist to explain this therapeutic effect. Accordingly, we evaluated
      studies that suggest that exercise is an effective treatment for MDD, and we
      explored potential mechanisms that could link adult neurogenesis, exercise and
      MDD. We conclude that there is evidence to support the hypothesis that exercise
      alleviates MDD and that several mechanisms exist that could mediate this effect
      through adult neurogenesis.

PMID- 16575426
TI  - Nuclear factor kappa B in the dorsal raphe of macaques: an anatomical link for
      steroids, cytokines and serotonin.
AB  - OBJECTIVE: Nuclear factor kappa B (NFkappaB) is a transcription factor that
      activates gene expression in response to proinflammatory cytokines, and elevated
      cytokines are associated with depression, which has a serotonergic component. We
      questioned (1) whether serotonin neurons contain NFkappaB, (2) whether NFkappaB
      detection with immunocytochemistry is changed in the dorsal raphe nucleus (DRN)
      by ovarian hormone treatment and (3) whether ovarian hormones regulate midbrain
      NFkappaB gene or protein expression. METHODS: Monkeys were spayed and treated
      with placebo, estrogen (E), progesterone (P) or E+P for 1 month (n = 4
      animals/treatment group), and the midbrain was harvested for immunocytochemistry
      and stereology. An antibody that detects nuclear location-specific (NLS)-NFkappaB
      p65 was applied, and the numbers of NLS-NFkappaB-immunopositive cells were
      counted in 9 sections of the DRN. Additional monkeys were used for Western blot
      analysis and quantitative reverse transcription-polymerase chain reaction (RT
      PCR) for NFkappaB p65. RESULTS: In placebo-treated macaques, neurons were double
      immunostained for serotonin and nuclear NFkappaB p65 throughout the DRN. The mean
      total number of NFkappaB-positive cells equalled 2178 (and standard error of the
      mean [SEM] 129) in the placebo group, 1631 (SEM 221) in the E-treated group, 2314
      (SEM 186) in the P-treated group and 1162 (SEM 100) in the E+P-treated group
      (analysis of variance p = 0.003). The E-treated and E+P-treated groups had a
      significantly lower density of cells stained positive for NFkappaB than the
      placebo or P-treated groups (post hoc). Unmasking of NLS-NFkappaB immunostaining
      in the DRN revealed dense immunostaining in the cytoplasm of large dorsal raphe
      neurons. There was no difference between treatment groups in the amount of
      NFkappaB p65 detected by Western blot or in the relative expression of NFkappaB
      p65 mRNA with quantitative RT-PCR. CONCLUSIONS: These observations are consistent
      with the notion that gene and protein expression of NFkappaB are constitutive but
      that ovarian hormones can decrease the nuclear location of NFkappaB in dorsal
      raphe neurons and, thereby, decrease the ability of NFkappaB to drive gene
      expression in response to cytokines.

PMID- 16575427
TI  - Alexithymia and stress-induced brain activation in cocaine-dependent men and
      women.
AB  - OBJECTIVE: Alexithymia means a reduced capacity to identify and describe one's
      own feelings. Both stress and an alexithymic response to stress can contribute to
      relapse into drug abuse, but to our knowledge the neural processing of an
      alexithymic response to stress in cocaine-dependent individuals has not been
      examined. METHODS: In a functional magnetic resonance imaging session,17 male and
      10 female abstinent cocaine-dependent subjects participated in script-guided
      imagery of neutral or stressful situations. Spatial preprocessing and statistical
      analysis of brain images were performed using Statistical Parametric Mapping
      Software (SPM2). Blood oxygen level-dependent contrasts between stress and
      neutral imagery were correlated voxelwise with scores on the 26-item Toronto
      Alexithymia Scale (TAS). RESULTS: Male cocaine users demonstrated a positive
      correlation between TAS scores and activation in the right putamen and middle
      frontal cortex during stressful, compared with neutral, imagery. In contrast, no
      brain regions showed a negative correlation with TAS scores. Female subjects
      demonstrated a negative correlation between TAS scores and activation in the
      right amygdala, thalamus, putamen, and left frontal and bilateral temporal
      cortices, and no positive correlations with TAS scores during stressful, compared
      with neutral, imagery. CONCLUSIONS: Women with greater alexithymic features
      showed reduced left-hemispheric cortical and right-hemispheric subcortical
      activation during processing of stress. However, men showed an opposite
      correlation in the right frontal cortex and putamen, suggesting that responses to
      stress in the putamen (activation v. deactivation) and frontal cortex (activation
      v. deactivation, as well as right v. left correlations) are critically different
      in association with alexithymia between male and female cocaine-dependent
      patients.

PMID- 16575428
TI  - Efficacy of escitalopram in the treatment of major depressive disorder compared
      with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a
      meta-analysis.
AB  - OBJECTIVE: Escitalopram is the most selective of the selective serotonin reuptake
      inhibitor (SSRI) antidepressants. Previous studies have suggested that
      escitalopram is superior to citalopram in efficacy. We conducted a meta-analysis
      of studies in which escitalopram was compared with other antidepressants to
      assess the relative efficacy of these agents. METHODS: Data from all randomized,
      double-blind studies in major depression in which escitalopram was compared with
      active controls (citalopram, fluoxetine, paroxetine, sertraline and venlafaxine
      XR [extended release]) were pooled. The 10 studies were conducted in both
      specialist settings and general practice. Patients met the criteria of the
      Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV),
      for major depressive disorder and were at least 18 years old. In all but 2
      studies, patients were required to have a score of 22 or more on the Montgomery
      Asberg Depression Rating Scale (MADRS). The primary outcome measure was the
      estimated difference in treatment effect in MADRS total score at the end of the
      study. Secondary outcome measures were the response to treatment (defined as a >
      or = 50% reduction in baseline MADRS total score) and remission rate (defined as
      MADRS total score < or = 12 at end of study). RESULTS: A total of 2687 patients
      were included in the analyses (escitalopram n = 1345, conventional SSRIs n =
      1102, venlafaxine XR n = 240). Escitalopram was superior to all comparators in
      overall treatment effect, with an estimated difference in treatment effect of
      1.07 points (95% confidence interval [CI] 0.42-1.73, p < 0.01), and in response
      (odds ratio [OR] 1.29, 95% CI 1.07-1.56, p < 0.01) and remission (OR 1.21, 95% CI
      1.01-1.46, p < 0.05) rates. In analysis by medication class, escitalopram was
      significantly superior to the SSRIs and comparable to venlafaxine, although the
      overall results do not necessarily reflect a significant difference between
      escitalopram and individual SSRIs. These results were similar in the severely
      depressed population (patients with baseline MADRS > or = 30). The withdrawal
      rate due to adverse events was 6.7% for escitalopram compared with 9.1% for the
      comparators (p < 0.05). CONCLUSIONS: In this meta-analysis, escitalopram showed
      significant superiority in efficacy compared with the active controls.

PMID- 16575430
TI  - Treatment guidelines for mania.

PMID- 16575429
TI  - The use of medroxyprogesterone acetate for the treatment of sexually
      inappropriate behaviour in patients with dementia.
AB  - Sexually inappropriate behaviour in a patient with dementia can be a problem for
      caregivers. Little research has been done concerning treatment for this
      behavioural disorder. The hormone medroxyprogesterone acetate (MPA) is a known,
      but infrequently used, treatment option. We describe a series of 5 cases in which
      MPA was used successfully to control inappropriate sexual behaviours in men with
      dementia.

PMID- 16575431
TI  - Speedup OS-EM Image Reconstruction by PC Graphics Card Technologies for
      Quantitative SPECT with Varying Focal-Length Fan-Beam Collimation.
AB  - In the paper, we present a new hardware acceleration method to speedup the
      ordered-subsets expectation-maximization (OS-EM) algorithm for quantitative SPECT
      (single photon emission computed tomography) image reconstruction with varying
      focal-length fan-beam (VFF) collimation. By utilizing the geometrical symmetry of
      VFF point-spread function (PSF), compensation for object-specific attenuation and
      system-specific PSF are accelerated using currently available PC video/graphics
      card technologies. A ten-fold acceleration of quantitative SPECT reconstruction
      is achieved.

PMID- 16575432
TI  - Astrocytic connectivity in the hippocampus.
AB  - Little is known about the functional connectivity between astrocytes in the CNS.
      To explore this issue we photo-released glutamate onto a single astrocyte in
      murine hippocampal slices and imaged calcium responses. Photo-release of
      glutamate causes a metabotropic glutamate receptor (mGluR)-dependent increase in
      internal calcium in the stimulated astrocyte and delayed calcium elevations in
      neighboring cells. The delayed elevation in calcium was not caused by either
      neuronal activity following synaptic transmission or by glutamate released from
      astrocytes. However, it was reduced by flufenamic acid (FFA), which is consistent
      with a role for adenosine triphosphate (ATP) release from astrocytes as an
      intercellular messenger. Exogenous ligands such as ATP (1 mircoM) increased the
      number of astrocytes that were recruited into coupled astrocytic networks,
      indicating that extracellular accumulation of neurotransmitters modulates
      neuronal excitability, synaptic transmission and functional coupling between
      astrocytes.

PMID- 16575433
TI  - The 3D quadrupole ion trap mass spectrometer as a complete chemical laboratory
      for fundamental gas-phase studies of metal mediated chemistry.
AB  - Electrospray ionization provides a "treasure trove" of metal containing ions
      whose fundamental reactivity can be studied via collision induced dissociation
      and ion-molecule reactions using the multistage mass spectrometry capabilities of
      the quadrupole ion trap mass spectrometer. Examples of metal mediated chemistry
      relevant to catalysis, C-C bond coupling, bioinorganic and supramolecular
      chemistry are highlighted.

PMID- 16575434
TI  - Dual mechanism of zinc-proline catalyzed aldol reactions in water.
AB  - The aldol reaction of acetone with aldehydes in aqueous medium under catalysis by
      zinc-proline (Zn(L-Pro)2) and secondary amines such as proline, (2S,4R)-4
      hydroxyproline (Hyp) and (S)-(+)-1-(2-pyrrolidinomethyl)pyrrolidine (PMP) is
      shown to proceed by an enamine mechanism, as evidenced by reductive trapping of
      the iminium intermediate, while the aldol reaction of dihydroxyacetone (DHA)
      under catalysis by zinc-proline and by general bases such as N-methylmorpholine
      (NMM) is shown to occur under rate-limiting deprotonation of the alpha-carbon and
      formation of an enolate intermediate.

PMID- 16575435
TI  - Metal salen complexes incorporating triphenoxymethanes: efficient, size selective
      anion binding by phenolic donors with a visual report.
AB  - A metal salen complex has been designed to orientate four phenol groups into a
      tetrahedral array that tightly binds fluoride ion though four OH...F hydrogen
      bonding interactions.

PMID- 16575436
TI  - Molecular building blocks approach to the assembly of zeolite-like metal-organic
      frameworks (ZMOFs) with extra-large cavities.
AB  - Two novel porous anionic zeolite-like metal-organic frameworks, rho-ZMOF and sod
      ZMOF, have been synthesized by metal-ligand-directed assembly of rigid and
      directional tetrahedral building units, InN4 synthesized in situ, and doubly
      deprotonated bis(bidentate) imidazoledicarboxylic acid ligands (HImDC) in the
      presence of different structure directing agents (SDAs).

PMID- 16575437
TI  - Photoinduced phase transition of coordinationally unsaturated d9 metal centers
      within the thermal hysteresis of the spin exchange interaction.
AB  - Diffraction evidence is presented that the structure of one-dimensional arrays of
      strained, coordinationally unsaturated d9 pseudo-Jahn-Teller centers is affected
      by excitation of the LMCT bands within the hysteresis region of the low
      temperature ferromagnetic-to-antiferromagnetic phase transition.

PMID- 16575439
TI  - A multiple switching bisthienylethene and its photochromic fluorescent
      organogelator.
AB  - A multiple switching fluorescent photochromic bisthienylethene bridged
      naphthalimide bearing cholesteryl groups was synthesized and its organogelator
      showed excellent photo-responsive and thermal reversible performance by light,
      thermal.

PMID- 16575438
TI  - Spectroscopic detection of Saxitoxin: an alternative to mouse bioassay.
AB  - Herein, we report the surface modification of quartz with a coumaryl-aza-crown-6
      derivative to detect Saxitoxin using fluorescence enhancement through
      Photoinduced Electron Transfer and the sensitivity with this system approaches
      the limit of the mouse bioassay which is the current benchmark for Saxitoxin
      detection.

PMID- 16575440
TI  - Tunable interchromophore electronic interaction of a merocyanine dye in hydrogen
      bonded supramolecular assemblies scaffolded by bismelamine receptors.
AB  - The absorption and fluorescence properties of a barbiturate-type donor-pi
      acceptor (D-pi-A) merocyanine dye are controlled by complexation with dimeric
      melamine receptors featuring different tether lengths.

PMID- 16575441
TI  - Impact of a conformationally restricted receptor on the BF2 chelated
      azadipyrromethene fluorosensing platform.
AB  - Conformational control of the receptor-fluorophore orientation of BF2 chelated
      azadipyrromethene sensors reveals two photophysically different modes of analyte
      triggered fluorescence switching both of which exhibit large off-on fluorescence
      intensity responses to the light input-output of the sensors in the visible red
      spectral region.

PMID- 16575442
TI  - Photoisomerization of cis,cis-1,4-diphenyl-1,3-butadiene in glassy media at 77 K:
      the bicycle-pedal mechanism.
AB  - The cis-trans photoisomerization of cis,cis-1,4-diphenyl-1,3-butadiene in a soft
      isopentane glass at 77 K gives significant two-bond photoisomerization in
      contrast to solution and hard glassy media where only one-bond photoisomerization
      takes place.

PMID- 16575443
TI  - Fast and sensitive analysis of DNA hybridization in a PDMS micro-fluidic channel
      using fluorescence resonance energy transfer.
AB  - Fluorescence resonance energy transfer has been used to illustrate its
      applicability to the sensitive detection of DNA hybridization reactions in a PDMS
      microfluidic channel.

PMID- 16575444
TI  - Functional liquid crystal films selectively recognize amine vapours and
      simultaneously change their colour.
AB  - During recent years, cholesteric liquid crystals have found only a few
      applications, one of them being temperature detection; in this study, however, we
      intend to show that the combination of cholesteric liquid crystals and molecules
      with a trifluoroacetyl function can be applied to optically detect amine vapours.

PMID- 16575445
TI  - Chiroptical inversion induced by sandwiching units in chiral polythiourethane.
AB  - Chiroptical behavior of a hydrogen-bond-regulated chiral polythiourethane segment
      was inversed by sandwiching sterically demanding segments in copolymers prepared
      by cationic ring-opening copolymerization of chiral cyclic thiourethanes derived
      from L-serine.

PMID- 16575446
TI  - An EXAFS study of the formation of a nanoporous metal-organic framework: evidence
      for the retention of secondary building units during synthesis.
AB  - EXAFS data measured from amorphous intermediates and crystallisation solutions
      provides the first evidence that trimeric iron oxide secondary building units
      remain intact during crystallisation of the metal-organic framework MIL-89 from
      starting materials to products.

PMID- 16575447
TI  - A new stepwise synthesis of a family of propylamines derived from diatom
      silaffins and their activity in silicification.
AB  - A new method for the stepwise synthesis of propylamines containing fragments of N
      methyl propylamine as found in diatom bioextracts is presented and their activity
      in silicic acid condensation is described.

PMID- 16575448
TI  - High basicity of phosphorus-proton affinity of tris
      (tetramethylguanidinyl)phosphine and tris
      (hexamethyltriaminophosphazenyl)phosphine by DFT calculations.
AB  - It is shown by approximate but reliable DFT calculations that the title compounds
      represent very strong superbases in gas phase and MeCN. In particular, tris
      (hexamethyltriaminophosphazenyl)phosphine has a proton affinity, PA, of 295.5
      kcal mol(-1) and records a pKa(MeCN) of 50 +/- 1 units.

PMID- 16575449
TI  - Experimental and computational studies on the solvent-controlled cluster
      isomerism of Ru3(H)(CO)9(NPPh3) and related dynamics.
AB  - The species Ru3(H)(mu3-NPPh3)(CO)9 occurs in the solid state as two isomers,
      characterized either by one capping hydride and three CO bridges (1a) or by one
      bridging hydride and all terminals COs (1b); key intermediates for the formation,
      fluxionality and solvent-dependent interconversion of the isomers are highlighted
      through a DFT MO analysis.

PMID- 16575450
TI  - Porous material for absorption and luminescent detection of aromatic molecules in
      water.
AB  - A two-dimensional porous framework, which was formed from neutral discrete
      hexanuclear copper clusters via self-assembly, exhibited highly selective
      absorption of aromatic molecules in water with special fluorescent response.

PMID- 16575451
TI  - Optical sensing system for ATP using porphyrin-alkaloid conjugates.
AB  - Tetrabrucin-porphyrin as a sensor for ATP was designed and tested; selectivity
      for ATP was proved in the presence of ADP and AMP.

PMID- 16575452
TI  - A nanoparticle-dendrimer conjugate prepared from a one-step chemical coupling of
      monofunctional nanoparticles with a dendrimer.
AB  - Gold nanoparticle-dendrimer conjugate clusters were prepared by a covalent
      coupling of monofunctional gold nanoparticles with a generation 5 PAMAM
      dendrimer.

PMID- 16575453
TI  - ESI-MS study on the aldol reaction catalyzed by L-proline.
AB  - The aldol reaction catalyzed by L-proline has been monitored and the accepted
      mechanism confirmed by intercepting and characterizing, for the first time, all
      the proposed intermediates by ESI-MS/MS.

PMID- 16575454
TI  - Probing the microenvironments in the grooves of Z-DNA using dan-modified
      oligonucleotides.
AB  - The environment-sensitive fluorophore dan (6-dimethylamino-2-acyl-naphthalene)-
      modified dC or dG bases were introduced into the Z-DNA forming sequence. It was
      demonstrated that both grooves of Z-DNA are more hydrated than those of B-DNA.
      Dan will be useful for probing the microenvironments in the grooves among the DNA
      polymorphs.

PMID- 16575455
TI  - Mesoscopically ordered organosilica and carbon-silica hybrids with uniform
      morphology by surfactant-assisted self-assembly of organo bis-silanetriols.
AB  - Long-range molecularly ordered organosilica and carbon-silica hybrids with
      uniform morphology have been synthesized by surfactant-assisted hydrolysis and
      self-assembly of biphenyl bridged organosilane, followed by thermal
      polycondensation and carbonization.

PMID- 16575456
TI  - Oligomers of cis-beta-norbornene amino acid: formation of beta-strand mimetics.
AB  - The oligomers of constrained cis-exo-beta-norbornene amino acid were synthesised
      and characterised by extensive NMR, CD, IR and MD studies. The results showed the
      formation of both right and left handed consecutive 6-membered hydrogen-bonded
      strands for [2S,3R] and [2R,3S] enantiomers, respectively.

PMID- 16575457
TI  - The Al(I) bisimidinate Al(DDP) as a metalloid NHC type ligand for Pd(0) complexes
      and clusters.
AB  - Two clusters with a Pd2 core and Al(DDP) (DDP = 2-((2,6-diisopropylphenyl)amino)
      4-((2,6-diisopropylphenyl)imino)-2-pentene) as a bridging ligand have been
      synthesized and characterized by single crystal structural analysis; the results
      suggest a strong similarity of the coordination properties of NHC's and the group
      13 analogue Al(DDP).

PMID- 16575458
TI  - Regio- and stereospecific ring opening of 1,1-dialkyl-2
      (aryloxymethyl)aziridinium salts by bromide.
AB  - Enantiomerically pure 2-(aryloxymethyl)aziridines are efficiently transformed
      into chiral N-(2-bromo-3-aryloxypropyl)amines via a regio- and stereospecific
      ring opening of the intermediate aziridinium salts, and the experimental results
      are rationalized on the basis of some high level ab initio calculations.

PMID- 16575459
TI  - Synthesis, stability and optimized photolytic cleavage of 4-methoxy-2-nitrobenzyl
      backbone-protected peptides.
AB  - We demonstrate the potential of 4-methoxy-2-nitrobenzyl as a Boc chemistry
      compatible fully reversible backbone modification for synthetic peptides.

PMID- 16575460
TI  - A supramolecular photosynthetic triad of slipped cofacial porphyrin dimer,
      ferrocene, and fullerene.
AB  - A supramolecular triad consisting of self-assembled imidazolyl-zinc-porphyrin
      dimer, ferrocene, and fullerene was successfully constructed, resulting in long
      lived charge separated species after efficient photoinduced electron transfer and
      charge shift reactions.

PMID- 16575461
TI  - Organocatalytic and direct asymmetric vinylogous Michael addition of alpha,alpha
      dicyanoolefins to alpha,beta-unsaturated aldehydes.
AB  - The first highly regio-, chemo-, diastereo- and enantioselective direct
      vinylogous Michael addition of alpha,alpha-dicyanoolefins to alpha,beta
      unsaturated aldehydes is described, employing readily available chiral
      alpha,alpha-diarylprolinol salts as iminium organocatalysts.

PMID- 16575462
TI  - Stem cell plasticity and carcinogenesis.
AB  - Presently, there is more and more talk about tumors being a disease connected
      with stem cells. Both stem cells and tumor cells have many similarities, and
      there is much evidence that microenvironment, cytokines and signal pathways
      control tissue specificities and have a significant role in the process of
      carcinogenesis. Recent experimental results show that stem cells and tumor stem
      cells apparently play a key role in carcinogenesis. Tumors grow up, thanks to the
      activity of just few stem cells that continuously produce other proliferating
      progenitor tumor cells. Generally, tumor elements are thought to be either
      undifferentiated, or dedifferentiated cells. Actually, the truth is that tumors
      are made of more or less differentiated cells with variable rate of
      differentiation. We suppose that under certain conditions tumor stem cells may
      participate in regeneration without giving rise to tumor formation. It is also
      presumed that we may reprogram tumor stem cells and progenitor cells in a certain
      period of time and so initiate development of normal tissue. However, till now
      the real relation between normal and tumor cells is not clear. Finally, we wish
      to remind that plasticity of tumor and normal cells cannot be separated but
      should be considered as individual phenomenon expressing certain condition of an
      organism in time. This communication is only a probe and introduction into a
      discussion aimed at better understanding of carcinogenesis from the view of
      processes at the stem cell level. Stimulation of stem cell activation may lead to
      prophylactic approaches for therapy and prevention in carcinogenesis.

PMID- 16575463
TI  - Surfing on prothymosin alpha proliferation and anti-apoptotic properties.
AB  - Prothymosin alpha is an extremely abundant nuclear oncoprotein-transcription
      factor essential for cell cycle progression and proliferation that has been
      recently suggested as an anti- apoptotic factor. Similarly to other oncoproteins,
      prothymosin alpha is overexpressed in a variety of cancer tissues and cell lines.
      The present review highlights on the proliferation and anti-apoptotic properties
      of prothymosin alpha and its possible role in cancer development.

PMID- 16575464
TI  - Ashkenazi founder BRCA1/BRCA2 mutations in Slovak hereditary breast and/or
      ovarian cancer families.
AB  - Germline mutations in BRCA1 and BRCA2 have been predominantly associated with the
      breast and ovarian cancers. Two mutations in BRCA1 (185delAG and 5382insC) and
      one mutation in BRCA2 (6174delT) are common in Ashkenazi Jewish population. To
      determine the proportion of these founder mutations, we analyzed DNA samples of
      120 Slovak hereditary breast and/or ovarian cancer (HBOC) suspected families. Two
      particular exons of BRCA1 (2, 20) and 11N segment of BRCA2 were screened by
      single strand conformation polymorphism (SSCP) followed by DNA sequencing of
      fragments showing abnormal migration pattern. Mutational analysis revealed that 7
      out of 20 (35%) families with detected BRCA1/BRCA2 pathogenic alteration harbored
      one of three Jewish mutations: five families with 5382insC, one family with
      185delAG and one family with 6174delT. Interestingly, we have noted a very rare
      phenotype, when 5382insC in BRCA1 co-segregated also with endometrial carcinoma.
      Similarly to the studies from other countries of Central and Eastern Europe, the
      most frequent pathogenic alteration found was 5382insC that accounted for 1/4 of
      all gene defects detected. Following the high proportion of Ashkenazi Jewish
      founder mutations in Slovak HBOC families, a pre-screening for at least 5382insC
      mutation in individuals at even moderate risk would be appropriate.

PMID- 16575465
TI  - Analysis of the relationship between socioeconomic factors and stomach cancer
      incidence in Slovenia.
AB  - An unequal population distribution of well-known major risk factors explains much
      of the variation in the incidence of stomach cancer worldwide. The aim of this
      study was to determine whether geographical variation of the stomach cancer
      incidence rate between Slovenia's municipalities during years 1995-2001 could
      partially be explained by variations in the socioeconomic status as an indirect
      stomach cancer risk factor. A composite measure of each region's socioeconomic
      status, labelled as deprivation index, was created from basic socioeconomic
      characteristics of each municipality using factor analysis. Municipalities'
      standardized incidence ratios for all stomach cancers and non-cardia stomach
      cancer were calculated. A fully Bayesian spatial model with a conditionally
      autoregressive prior was applied using Markov chain Monte Carlo techniques and
      WinBUGS software. Spatially smoothed maps of stomach cancer incidence rates by
      192 Slovenian municipalities show a clear west-to-east gradient. This pattern
      resembles the geographical variation of socioeconomic indices, but these indices
      are not significant predictors of stomach cancer incidence. Geographical
      variation of stomach cancer incidence in Slovenia could be partially explained by
      the heterogeneous socioeconomic characteristics of its municipalities. It is
      possible that the socioeconomic status indices used in our study were not enough
      powerful predictors of stomach cancer risk. Some further methodological research
      is needed to explain why this association was not statistically evident with the
      current modeling approach.

PMID- 16575466
TI  - A disconnect between antitumor and antiangiogenic effects of fluvastatin in vitro
      and in vivo.
AB  - The possible role of statins in cancer is controversial. Indeed, among the
      multiplicity of biological effects ascribed to these widely used cholesterol
      lowering agents some could, at least in theory, inhibit tumor growth (e.g. by
      inhibiting Ras oncoproteins), while other actions are inert, or may even
      stimulate cancer aggressiveness (e.g. through promoting neovascularization). In
      order to address some of these controversies, we set out to compare the effects
      of statins on growth of cancer and endothelial cells in vitro, to the impact of
      these drugs on angiogenesis-dependent expansion of the corresponding tumors in
      vivo. Water-soluble fluvastatin was used at concentrations (0-800 ng/ml) against
      human umbilical vein endothelial cells (HUVEC), and several well-characterized
      cancer cell lines in culture, including: carcinoma (LLC), melanoma (B16F1) and
      fibrosarcoma driven by mutant H-ras (528ras1). Endpoints were based on 3H
      thymidine incorporation assay, cell morphology and tumorigenicity in mice. The
      growth inhibitory effects of fluvastatin varied among cancer cell lines
      (LLC>B16F1>528ras1), irrespectively of their mutant H-ras status. Fluvastatin
      also blocked the action of angiogenic factors on cultured endothelial cells, but
      was relatively ineffective against highly angiogenic and aggressive tumors both
      in young mice (6-8 weeks), and in less aggressively growing tumors in aged (80-90
      weeks) mice. Thus, antitumor and antiangiogenic activity of fluvastatin in vitro
      is not recapitulated in vivo. Tumors may display a form of resistance to statins
      through a mechanism operative only in vivo.

PMID- 16575467
TI  - Raltitrexed plus oxaliplatin in the second-line treatment of metastatic
      colorectal cancer.
AB  - The primary endpoint of this study was to evaluate the efficacy (objective
      response rate; ORR) of combined chemotherapy with raltitrexed plus oxaliplatin as
      second-line treatment in patients with metastatic colorectal cancer (CRC).
      Secondary endpoints were overall survival (OS), time to progression (TTP) and
      toxicity (NCI-CTC criteria). The target population were patients with metastatic
      colorectal adenocarcinoma who progressed after first-line chemotherapy. Treatment
      consisted of raltitrexed 3 mg/m2 as a 15-minute intravenous (IV) infusion
      followed 45 minutes later by oxaliplatin 130 mg/m(2) IV as a 2-h infusion on Day
      1, repeated every 3 weeks until further disease progression (PD), unacceptable
      toxicity or the decision of the patient. A total of 51 patients, all with WHO
      performance status 0-2 received a median of 6 treatment cycles (range 1-11).
      After 3 cycles, 8 of the 47 evaluable patients (17%) had experienced an ORR, 28
      patients (59.6%) had experienced stable disease (SD) and 11 patients (23.4%) had
      PD. After 6 cycles, 1 of the 29 evaluable patients (3.5%) had an ORR, 13 patients
      (44.8%) had SD and 15 patients (51.7%) had PD. After a median follow-up of 48.9
      weeks, median TTP was 18 weeks and median overall survival was 54.4 weeks.
      Treatment was well tolerated; grade 3 toxicities occurred in only 5/51 patients
      (9.8%). The most common toxicities were paraesthesia (62.7%), diarrhoea (23.5%),
      nausea (41.2%), vomiting (33.3%), hepatotoxicity (25.5%), and hematological
      toxicity (41.2%). In conclusion, the combination of oxaliplatin plus raltitrexed
      appears to be effective and well tolerated as second-line therapy in patients
      with disseminated CRC.

PMID- 16575468
TI  - Expression of MDR proteins in breast cancer and its correlation with some
      clinical and pathological parameters.
AB  - The aim of this work was to determine the expression of the multidrug resistance
      (MDR) proteins, namely MDR1 (P-glycoprotein), MRP1 (multidrug resistance-related
      protein) and LRP (lung resistance-related protein), in 87 samples of breast
      carcinoma. Detection of these proteins was provided by using indirect enzymatic
      immunohistochemistry. Our findings were compared with the other clinical and
      pathological parameters: expression of Her2/neu, estrogen receptor status (ER),
      progesteron receptor status (PR), histological grade and regional lymph node
      status. For statistical analysis, non-parametric two sided Mann-Whitney-U test
      was used. Majority of breast carcinoma specimens show positivity for these
      proteins. The MDR1 and MRP1 signal was found in the cytoplasm of cancer cells.
      The expression of LRP was detected in the cytoplasm close to the nuclear
      membrane. The samples were positive for MDR1 protein in 57%, for MRP1 in 84% and
      for LRP in 79%. Comparing our results with other clinical and pathological
      parameters, negative correlation between ER, PR and MDR1 expressions and
      histological grading status was found. No associations were observed between the
      MRP1 and LRP proteins and histological grading, as well as between the expression
      of three MDR proteins and the other clinically relevant parameters. In
      conclusion, high frequency of expression of MDR proteins in breast carcinoma
      cells suggests, that these proteins might be an important factor of drug
      resistance in breast carcinoma. Nevertheless, the negative correlation between
      the histological grade of malignancy of tumor and the expression of ER, PR and
      MDR1 indicates possible influence of progressive tumor cell de-differentiation.
      However, this finding has to be confirmed in additional evaluations.

PMID- 16575469
TI  - Myelodysplastic syndromes according to FAB and WHO classification. Single center
      experience.
AB  - The results of clinical and laboratory observations of 119 MDS patients divided
      acc. to FAB, and - after excluding RAEB-t and CMML groups -- of 95 patients
      divided accordingly to WHO classification are presented. The diagnosis of MDS was
      based on medical interview, physical examination, blood biochemistry, peripheral
      blood (PB) and bone marrow (BM) cytomorphology and cytochemistry, trephine biopsy
      and cytogenetic examination. All hematologic examinations were done according to
      routine methods. Cytogenetic analyses were carried out on BM cells from 24-48 h
      cultures in standard conditions. At least 15-20 GTG-banded metaphases were
      analyzed in every patient. The survival time (ST) of patients differed
      significantly between the FAB or WHO groups, with p=0.0004 for FAB and p=0.02 for
      WHO. The progression to AML was more common in less favorable groups, with
      p=0.0001 for FAB and p=0.00016 for WHO. The distribution of IPSS prognostic index
      among the groups showed statistically significant difference (p=0.0004 for FAB,
      and p=0.0001 for WHO), whereas the distribution of karyotypic abnormalities did
      not. However, in univariate analysis statistically significant influence on ST
      showed, beside the both classification systems: cytogenetics, the presence of
      blasts in PB, age and IPSS index. In multivariate analysis the sole independent
      prognostic factors were: PB blasts and cytogenetics. The authors conclude that
      the WHO classification offers a good prognostic tool for MDS patients. However,
      the karyotype and the presence of blasts in PB should always be taken into
      account.

PMID- 16575470
TI  - The regulation of human adrenomedullin (AM) and tumor necrosis factor alpha (TNF
      alpha) receptors on human epithelial carcinoma (HeLa) cells. The role of AM
      secretion in tumor cell sensitivity.
AB  - The cytostatic cytokine tumor necrosis factor-alpha (TNF-alpha) and proliferative
      hormone adrenomedullin (AM) are abundantly expressed in human tumors. However,
      little is known about mechanism (s) through which TNF-alpha and AM exert their
      regulatory effects, especially in the regulation of proliferative activity in
      malignant cells. Also the role played by TNF-alpha in pathogenesis and treatment
      of cancer (targeted cancer therapy) remains less understood. The purpose of this
      study was therefore to characterize the significance of TNF-alpha induced
      apoptosis with down-regulation of plasma-membrane TNF-alpha receptors and up
      regulation of AM receptors with increased production of human AM mRNA, i.e.
      mechanisms that subsequently control aberrant cellular proliferation in malignant
      cells. Cytotoxicity, and the whole cell ligand binding assays for TNF-alpha and
      AM receptors, and RIA-assays of AM production were accomplished in control
      experiments using pharmacologically pretreated HeLa cells. AM increased
      proliferation of HeLa cells and AM antagonist (Ala6,21)AM(22-52) significantly
      antagonized this increase. TNF-alpha inhibitor of cell growth actinomycin-D
      significantly increased cytotoxicity of TNF-alpha in HeLa cells. Hypoxia
      increased TNF-alpha production and increased surface-membrane [125I]AM binding.
      Tumor promotor PMA and histamine down-regulated specific binding of [125I]TNF-
      alpha on HeLa cells. Mitogenic peptide endothelin-1 increased and specific ET-1
      antagonist BQ123 and significantly reduced AM binding. Production of AM in HeLa
      cells markedly increased after exposure to hypoxia >ET-1 >PMA. BAY11-7082 at
      concentrations that inhibited IkappaB phosphorylation and thus nuclear
      translocation and surface membrane TNF-alpha expression increased AM specific
      binding. Pretreatment of cells inhibitor of HMGCoA reductase inhibitor VULM1457
      significantly increased the total number of specific [125I]AM binding sites on
      HeLa cells. These results suggest relative and contradictory TNF-alpha and AM
      surface-membrane receptor signaling in HeLa cells and findings reveal a novel
      proliferative mechanisms that control AM production and thus oncogenic signaling
      in cells. This implies that several putative inhibitors of TNF-alpha and AM
      signaling may be considered in oncology for treatment of tumors otherwise
      nonresponding to cytostatic therapy.

PMID- 16575471
TI  - Amplification of AML1 gene in association with karyotype, age and diagnosis in
      acute leukemia patients.
AB  - The AML1 gene, located in the chromosomal band 21q22, belongs to the runt domain
      family of genes and encodes the subunit of the core-binding factor (CBF). AML1 is
      normally expressed in all hematopoietic lineages and is essential for the
      transcriptional regulation of a number of hematopoietic specific genes. In acute
      leukemia three types of abnormality of AML1 have been observed -- chromosomal
      translocations, point mutation and duplication or amplification of the
      unrearranged gene. The most common origin of extra copies of the AML1 gene is
      polysomy of chromosome 21 or a partial duplication of the long arm of chromosome
      21, less frequently ring, isochromosome or the tandem repetition of chromosome
      21. In the study 13 children and 5 adults with ALL and AML or MDS, respectively,
      have been included. Using standard G-banding and dual color FISH analyses, gain
      of AML1 originated in polysomy of chromosome 21 in each group of patients was
      proved. True high-level amplification was not observed but some uncommon changes
      in noteworthy association with other chromosome aberrations, age or diagnoses
      were presented.

PMID- 16575472
TI  - Phenotypic quantitative features of patients with acute myeloid leukemia.
AB  - The recent WHO classification for acute myeloid leukemias (AML) separates
      entities by recurrent cytogenetic abnormalities and immunophenotypic features
      presenting prognostic impact. We have examined the expression of several lineage
      and maturation linked antigens used in routine immunophenotyping of patients with
      de novo AML, using a 3-color two-step panel. Cases were diagnosed by peripheral
      blood counts, bone marrow cytology, cytochemistry, cytogenetics and
      immunophenotyping (CD2, CD3, CD7, CD19, CD13, CD33, myeloperoxydase -- MPO, CD14,
      CD15, HLA-DR, CD34, CD56 and CD45). Antigen expression was measured by mean
      fluorescence intensity (MFI) by flow cytometry (Paint-a-gate software). Thirty
      five patients were analyzed. Median age: 51 years (15-79). Predominant FAB types
      were M2 and M4. In 6 cases more than one phenotypically distinct blast
      subpopulation could be detected. Although our set was small, we tried to analyze
      the impact of MFI of the examined antigens on the overall survival of the
      patients. In Cox univariate analysis, age, peripheral leukocytes (WBC) at
      diagnosis, MFI of CD45, and MPO were significant for worse a survival. In the
      multivariate analysis only MFI of CD45 and WBC remained in the model (p=0.018 and
      p=0.014 respectively). After bootstrap resampling, MFI of CD45 entered the model
      in 69%, WBCin 60%, age in 42% and MFI of MPO in 35% of the sets. Analysis of
      antigen expression by MFI permitted to detect cases presenting phenotypically
      distinct blast subpopulations. This may represent a pitfall in studies of minimal
      residual disease by flow cytometry, as chemotherapy may select one of these
      subsets.

PMID- 16575473
TI  - Prostate-specific antigen value as a marker in breast cancer.
AB  - The immunoexpression of prostate-specific antigen in breast cancers has been well
      established, but the role of this extra-prostate PSA appears to be a complex,
      poorly understood and of doubtful prognostic value. In this context, our aim was
      to evaluate PSA in breast carcinomas and to compare the results with several
      established prognostic markers of breast cancer: estrogen and progesterone
      receptors status, HER2/neu status, histological type of tumor, grade of
      differentiation, stage, tumor size, nodal and menopausal status. We have
      immunohistochemically assessed 53 breast carcinomas for PSA, ER, PR and
      oncoprotein HER2/neu status. The relationship between the clinical and
      histopathological markers was analyzed by chi-square test. In the present study
      PSA was expressed in 60.3% of cases, and we have found a significant correlation
      with the histological type and HER2/neu negative status in premenopausal women.
      No statistically significant difference was found between PSA positivity and
      menopausal status of the patients, nodal status, estrogen and progesterone
      receptors, HER2/neu status in postmenopausal patients, tumor size or histological
      grade. We conclude that in our study PSA can not be considered as a valuable
      independent prognostic factor in breast carcinoma. As long as the majorities of
      PSA positive carcinomas were small in size, early stage, better and moderately
      differentiated, HER2/neu negative and 70% of ER/PR positive carcinomas expressed
      PSA, it might be useful as a marker for a subset of breast cancers with better
      prognosis, which could respond to endocrine therapy, in correlation with other
      prognostic markers.

PMID- 16575474
TI  - Resistance to glucocorticoids in childhood acute lymphoblastic leukemia: impact
      of relationship between ex vivo sensitivity and in vivo concentration on risk
      factor analysis.
AB  - Resistance to glucocorticoids remains one of the main obstacles in therapy of
      childhood acute lymphoblastic leukemia (ALL). The aim of the study was the
      analysis of relationship between ex vivo drug resistance of prednisolone and
      dexamethasone and exposure to these drugs in childhood ALL, with respect to risk
      factor analysis. Ex vivo resistance to both glucocorticoids was compared to
      maximum drug concentration achievable in body fluids, calculated in mathematical
      model. Drug resistance to vincristine and L-asparaginase, expression of multidrug
      resistance and apoptosis proteins was also determined. Concentration of both
      glucocorticoids in extracellular fluid was higher than drug resistance in the
      following groups of patients: in initial ALL patients, in patients staying in
      remission during follow-up, and in prednisolone good responders. Factors
      significant by multivariate analysis were early bone marrow response by day 15
      and concentration of prednisolone higher than ex vivo prednisolone resistance.
      For initial ALL patients with determined response to initial prednisolone
      monotherapy, factors significant by univariate analysis were early bone marrow
      response, and exposure to glucocorticoids higher than ex vivo resistance to these
      drugs. No factor was significant by multivariate analysis in this group. Risk
      factor analysis showed that concentration of prednisolone and dexamethasone
      higher than respective ex vivo drug resistance, is a strongest prognostic factor
      in childhood ALL.

PMID- 16575475
TI  - Cardiac function and cardiopulmonary performance in patients after treatment for
      non-Hodgkin's lymphoma.
AB  - Authors conducted a one-year prospective study to determine whether CHOP regimen
      (cyclophosphamide, doxorubicin, vincristin, and prednisone), used in the
      treatment of aggressive non-Hodgkin s lymphoma, is associated with the presence
      of an early impairment of cardiac function. Forty seven patients were
      prospectively examined (27 male and 20 female) aged 49+/-14 years who were
      treated with CHOP regimen. Rest echocardiography was performed at baseline and
      one-year control. Cardiopulmonary exercise test was carried out at one-year
      control examination. The ejection fraction (EF), parameters of diastolic
      function, myocardial performance index (MPI), and pVO2 were used as parameters of
      cardiopulmonary performance. The cumulative dose (CD) of doxorubicin was 277+/-56
      (300 mg/m(2)) was given. The baseline EF 64+/-5% (64%) decreased to 58+/-7% (57%)
      at the one-year control (p<0.0001). 23% of patients exhibited a drop in EF >10%
      during the follow-up. 43% revealed a pathologically increased value of MPI >0.55,
      and 47% impaired diastolic function compared to the baseline values,
      respectively. 21% of patients exhibited a decrease of pVO(2) < 20 ml/kg/min, and
      17% pVO(2) < 80% of the reference value, respectively. None of the patients
      developed signs of heart failure. The Doppler parameters of both diastolic and
      global LV function were the most affected measures and significantly influenced
      the cardiopulmonary performance. Multivariate analysis showed that CD > or =300
      mg/m(2) (OR=8.08; p<0.05) and the presence of risk factors (OR=9.48; p<0.008) are
      the best predictors of cardiotoxicity. The results show that subclinical cardiac
      impairment was frequent in patients receiving the CHOP regimen with safe
      cumulative doses of doxorubicin. The value of described changes for the
      development of heart failure has to be assessed during the prospective follow-up.

PMID- 16575477
TI  - [Sleifting from continuing medical education to continuing professional
      development. The example of the German assessment system for surgeons].
AB  - In addition to medical knowledge and skills, medical competency includes critical
      self-refection and professional mistake management, the ability to manage the
      administrative workload and techniques of professional communication and
      leadership. In addition to that physicians have to develop social competency and
      empathy for staff members and patients. Continuing medical education (CME)
      focuses on continuing development of medical knowledge and skills. To develop the
      additional aspects of medical competency the concept of medical education has to
      be broadened to continuing professional development (CPD). In different European
      countries and North America CPD includes a regular mandatory system to evaluate
      medical competency. Assessment systems like PAR in Alberta/Canada provide doctors
      with a 360 degree analysis of their daily work, showing the potential for future
      improvement. ECKO (Evaluation of Surgical Competency) is an adapted assessment
      system for German surgeons available on a voluntary basis. For the first time in
      Germany physicians are able to take part in a strength-weakness analysis of their
      daily work. They receive recommendations on practice improvement and an
      educational prescription for individual further education.

PMID- 16575478
TI  - Genetic analysis of calicivirus genomes detected in intestinal contents of
      piglets in Japan.
AB  - Enteric caliciviruses, noroviruses, and sapoviruses are emerging pathogens
      responsible for diarrhea or gastroenteritis in their respective hosts. In this
      study, swine enteric caliciviruses were detected in ten samples of intestinal
      contents from 24 piglets in Japan by reverse transcription-polymerase chain
      reaction using a broadly reactive primer pair (P290/289) that targeted the highly
      conserved RNA polymerase regions of the enteric caliciviruses. From the positive
      samples, the entire viral genome of strain K7/JP and 3'-end parts of the genomes
      of strains K5/JP and K10/JP were cloned and sequenced. K7/JP had an RNA genome of
      7144 bases, excluding its 3' poly (A) tail. The K7/JP genome possessed two open
      reading frames and characteristics common to sapoviruses. In phylogenetic
      analysis using amino acid sequences of VP1, K5/JP was demonstrated to be close to
      the noroviruses previously detected in pigs, and K7/JP and K10/JP were considered
      to be classified as a new genogroup of sapoviruses.

PMID- 16575476
TI  - The Cajal body: a meeting place for spliceosomal snRNPs in the nuclear maze.
AB  - Spliceosomal small nuclear ribonucleoprotein particles (snRNPs) are essential pre
      mRNA splicing factors that consist of small nuclear RNAs (snRNAs) complexed with
      specific sets of proteins. A considerable body of evidence has established that
      snRNP assembly is accomplished after snRNA synthesis in the nucleus through a
      series of steps involving cytoplasmic and nuclear phases. Recent work indicates
      that snRNPs transiently localize to the Cajal body (CB), a nonmembrane-bound
      inclusion present in the nuclei of most cells, for the final steps in snRNP
      maturation, including snRNA base modification, U4/U6 snRNA annealing, and snRNA
      protein assembly. Here, we review these findings that suggest a crucial role for
      CBs in the spliceosome cycle in which production of new snRNPs--and perhaps
      regenerated snRNPs after splicing--is promoted by the concentration of substrates
      in this previously mysterious subnuclear organelle. These insights allow us to
      speculate on the role of nuclear bodies in regulating the dynamics of RNP
      assembly to maintain a functional pool of factors available for key steps in gene
      expression.

PMID- 16575479
TI  - A case of scrapie in a sheep carrying the lysine-171 allele of the prion protein
      gene.
AB  - Susceptibility to scrapie in sheep depends on the host PrP genotype. No data
      about the linkage of the rare ARK allele to differential scrapie susceptibility
      are currently available. Several tissues isolated from sheep from an Italian
      scrapie outbreak and carrying the ARK allele were examined for the presence of
      the pathological prion protein. A weak positivity was detected only by Western
      blot in the brainstem of one ARK/ARH sheep. This result shows that the ARK allele
      does not confer full resistance against scrapie and that the allele needs to be
      studied further before it can be considered for breeding purposes.

PMID- 16575480
TI  - Characterization of a recombinant encephalomyocarditis virus expressing the
      enhanced green fluorescent protein.
AB  - A recombinant encephalomyocarditis virus (rEMCV2887A-egfp) expressing the
      enhanced green fluorescent protein (EGFP) was produced. The EGFP gene was
      inserted in frame within the leader protein coding sequence of a full-length cDNA
      clone of EMCV. RNA transcripts derived from the recombinant full-length cDNA were
      synthesized in vitro and transfected into BHK-21 cells. The recombinant
      transcript RNA remained infectious despite the insertion of EGFP as shown by
      cytopathic effects on BHK-21 cells and by propagation of the rescued virus. The
      replication kinetics in BHK-21 cells and the pathogenicity in mice of rEMCV2887A
      egfp did not differ significantly from that of the parental virus. The
      recombinant virus was shown to produce fluorescence in infected cells after at
      least five passages in BHK-21 cells. However, a decrease of EGFP expression was
      observed following serial passages, and this was associated with the accumulation
      of deletion mutations within the EGFP gene. Nevertheless, using EGFP
      autofluorescence, infected cells were easily detected in the brain of mice
      infected with the first-passage recombinant virus. These data demonstrate that
      rEMCV2887A-egfp could be a useful tool to study virus dissemination and
      pathogenicity when used at low passages.

PMID- 16575481
TI  - Size and position of truncations in the carboxy-terminal region of major capsid
      protein VP1 of hamster polyomavirus expressed in yeast determine its assembly
      capacity.
AB  - The hamster polyomavirus major capsid protein VP1 was modified in its carboxy
      terminal region by consecutive truncations and single amino acid exchanges. The
      ability of yeast-expressed VP1 variants to form virus-like particles (VLPs)
      strongly depended on the size and position of the truncation. VP1 variants
      lacking 21, 69, and 79 amino acid (aa) residues in their carboxy-terminal region
      efficiently formed VLPs similar to those formed by the unmodified VP1 (diameter
      40-45 nm). In contrast, VP1 derivatives with carboxy-terminal truncations of 35
      to 56 aa residues failed to form VLPs. VP1 mutants with a single A336G aa
      exchange or internal deletions of aa 335 to aa 346 and aa 335 to aa 363 resulted
      in the formation of VLPs of a smaller size (diameter 20 nm). These data indicate
      that certain parts of the carboxy-terminal region of VP1 are not essential for
      pentamer-pentamer interactions in the capsid, at least in the yeast expression
      system used.

PMID- 16575483
TI  - Tissue Doppler imaging--a sensible imaging option for the sensitive heart.

PMID- 16575482
TI  - Reproducibility of intravascular ultrasound radiofrequency data analysis:
      implications for the design of longitudinal studies.
AB  - OBJECTIVES: The purpose of this study was to assess in vivo the reproducibility
      of tissue characterization using spectral analysis of intravascular ultrasound
      (IVUS) radiofrequency data (IVUS-VH). BACKGROUND: Despite the need for
      reproducibility data to design longitudinal studies, such information remains
      unexplored. METHODS AND RESULTS: IVUS-VH (Volcano Corp., Rancho Cordova, USA) was
      performed in patients referred for elective percutaneous intervention and in whom
      a non-intervened vessel was judged suitable for a safe IVUS interrogation. The
      IVUS catheters used were commercially available catheters (20 MHz, Volcano Corp.,
      Rancho Cordova, USA). Following IVUS-VH acquisition, and after the disengagement
      and re-engagement of the guiding catheter, an additional acquisition was
      performed using a new IVUS catheter. Fifteen patients with 16 non-significant
      lesions were assessed by 2 independent observers. The relative inter-catheter
      differences regarding geometrical measurements were negligible for both
      observers. The inter-catheter relative difference in plaque cross-sectional area
      (CSA) was 3.2% for observer 1 and 0.5% for observer 2. The limits of agreement
      for (observer 1 measurements) lumen, vessel, plaque and plaque burden
      measurements were 0.82, -1.10 mm(2); 0.80, -0.66 mm(2); 1.08, -0.66 mm(2); and
      5.83, -3.89%; respectively. Limits of agreement for calcium, fibrous,
      fibrolipidic and necrotic core CSA measurements were 0.22, -0.25 mm(2); 1.02, 
      0.71 mm(2); 0.61, -0.65 mm(2); and 0.43, -0.38 mm(2) respectively. Regarding the
      inter-observer agreement, the limits of agreement for lumen, vessel, plaque and
      plaque burden measurements were 2.61, -2.09 mm(2); 2.20-3.03 mm(2); 1.70, -3.04
      mm(2); and 9.16, -16.41%; respectively, and for calcium, fibrous, fibrolipidic
      and necrotic core measurements of 0.08, -0.09 mm(2); 0.89, -1.28 mm(2); 0.74, 
      1.06 mm(2); and 0.16, -0.20 mm(2); respectively. CONCLUSIONS: The present study
      demonstrates that the geometrical and compositional output of IVUS-VH is
      acceptably reproducible.

PMID- 16575484
TI  - Prevalence of incontinence in women with benign joint hypermobility syndrome.
AB  - The objective of this study was to determine whether the prevalence of urinary
      and anal incontinence in women with benign joint hypermobility syndrome (BJHS)
      was more than in a control group without this condition. The International
      Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and the
      Manchester Health Questionnaire were sent to 30 patients with benign joint
      hypermobility syndrome and 30 healthy women without this condition and results
      were compared. It was found out that the prevalence of urinary incontinence in
      the study group we surveyed was 18/30 and in the control group was 9/30 (60 vs
      30%; p=0.037). Twenty-three percent (7/30) of the women with BJHS had a problem
      with anal incontinence but none of the controls had problems with anal
      incontinence (23 vs 0%; p=0.01). Therefore, the prevalence of both urinary and
      anal incontinence appears to be significantly higher in women with BJHS when
      compared to women without this condition.

PMID- 16575485
TI  - Needle suspension of the bladder neck for stress urinary incontinence: objective
      results at 11 to 16 years.
AB  - We analyzed the objective and subjective long-term outcomes of women who
      underwent needle suspension of the bladder neck 11 to 16 years previously. A
      total of 132 women underwent a needle suspension procedure at our institution
      between 1986 and 1991. In a retrospective cohort study, 63 of these women were
      evaluated by clinical examination, urodynamic testing, cough stress test, and
      standardized personal interview. Objective continence was defined as no loss of
      urine either during cystometry or during coughing with the bladder filled to 300
      ml. The objective continence rate was 56% (25/45) and the subjective continence
      rate was 41% (26/63). With regard to patient satisfaction, only 38% (24/63) of
      the studied patients considered themselves completely cured, and an additional
      30% (19/63) improved. The objective and subjective long-term results of needle
      suspension of the bladder neck are modest. Long-term complications such as
      urinary retention and overactive bladder syndrome are rare.

PMID- 16575486
TI  - Trans-obturator surgery for stress urinary incontinence: 1-year follow-up of a
      cohort of 52 women.
AB  - This study was a 1-year follow-up of a cohort of 52 women who underwent trans
      obturator tape (TOT) procedures using Obtape. Follow-up information was available
      for 45/52 (87%) women. The rate of erosions was 8/52 (15%). Among 34 women
      examined, 26% experienced tenderness on palpation of operative site, and 72% were
      objectively cured on pad test. Forty women completed questionnaires (median
      Incontinence Impact Questionnaire-7, 0; median Urogenital Distress Inventory-6,
      17) and of those, 93% would recommend TOT to a friend. We found a high rate of
      erosions among our cohort. Our high rate of erosions may be a result of our
      review of the majority of the cohort, and it is likely related to the specific
      device used (Obtape). The majority of women were satisfied with the outcome.
      Before introducing new procedures into widespread clinical practice, it is
      important to rigorously investigate their outcomes.

PMID- 16575488
TI  - The need for randomised controlled trials in urogynaecology.

PMID- 16575487
TI  - Impact of stress urinary incontinence and overactive bladder on micturition
      patterns and health-related quality of life.
AB  - We examined the impact of stress urinary incontinence (SUI) and overactive
      bladder (OAB) on micturition habits and health-related quality of life (QOL). A
      total of 250 Korean women were included in the study. The Medical Outcomes Study
      Short Form (SF-36) and the King's Health Questionnaire (KHQ) were used to assess
      QOL in the patient (SUI, n=158 and OAB, n=92) and control (n=70) groups. A
      control group was recruited at the Health Promotion Center of our hospital. Each
      of the dimension scores in the SF-36 represents better health, while that of the
      KHQ does worse health perception. On the frequency-volume charts, patients with
      OAB had more nighttime voids than those with SUI (P=0.001). Of the eight domains
      in the SF-36 questionnaire, four domains were significantly different between the
      control and OAB groups. Patients with SUI had a significantly lower score on one
      domain than the controls. Between the SUI and OAB groups, only one domain showed
      a significant difference. Regarding the KHQ, all domain scores in control
      subjects were significantly lower than those in the SUI and OAB groups. Between
      the SUI and OAB groups, the OAB group had higher scores on 'general health
      perception' and 'sleep/energy disturbances', while the scores of 'physical
      limitations' and 'severity measures' were higher in the SUI group. Women with OAB
      have a higher number of nocturic episodes than those with SUI, but the QOL is not
      less affected by SUI than by OAB. Furthermore, simultaneous disease-specific QOL
      instruments should be used in the evaluation of urinary incontinence because the
      generic QOL instrument is not a sensitive tool for measuring QOL in this
      population.

PMID- 16575490
TI  - Unusual long bone and metacarpo-carpal abnormalities in a case of pseudo
      pseudohypoparathyroidism.
AB  - A case of pseudo-pseudohypoparathyroidism (PPH) with shortening of the left femur
      and tibia and coalition of the base of the fourth metacarpals with capitatum and
      hamatum in bilateral wrist joints was presented. Involvement of the fourth digits
      both in hands and feet were more prominent on the left side, with shortening of
      the left leg.

PMID- 16575489
TI  - Anti-myeloperoxidase antibodies enhance phagocytosis, IL-8 production, and
      glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3
      antibodies leading to activation-induced cell death of the neutrophils.
AB  - Anti-neutrophil cytoplasmic antibodies (ANCA) not only are triggered by target
      protein myeloperoxidase (MPO) and proteinase 3 (PR3) of polymorphonuclear
      neutrophil (PMN) but also react with primed PMN to exert the inflammatory process
      in vasculitis syndrome. To clarify the crucial role of PMN in ANCA-associated
      vasculitis and the related mechanism, PMN was cultured with monoclonal antibody
      MPO-ANCA and PR3-ANCA to determine the function of phagocytosis, Interleukin- 8
      (IL-8) production, glucose uptake, and TNF-related apoptosis induced ligand
      (TRAIL) production. The spontaneous membrane expression of MPO and PR3 on PMN
      could be significantly increased by lipopolysaccharide (LPS) and TNF-alpha, but
      not by IL-8 or GRO-alpha. The PMN-stimulating activity of ANCA was demonstrated
      by enhancing phagocytosis, IL-8 production, and glucose uptake that was more
      prominent by MPO-ANCA. The PMN stimulation by ANCA was not through protein
      kinase, H2O2, or superoxide anion radicals as their inhibitors exerted no effect
      on ANCA-mediated activation. On the other hand, ANCA also accelerated PMN
      apoptosis and increased TRAIL production. These results demonstrate that
      activation-induced cell death (AICD) mechanism could be initiated in PMN with
      existence of ANCA. In conclusion, MPO-ANCA is more potent in stimulating PMN than
      PR3-ANCA. ANCA-activated PMN is not only responsible for the amplified
      inflammatory process in blood vessel but also initiates immune circuit via
      triggered macrophage/monocyte by apoptotic PMN through the mechanism of AICD
      elicited by ANCA.

PMID- 16575491
TI  - Rare association of antiphospholipid syndrome and Takayasu arteritis.
AB  - The antiphospholipid syndrome (APS) is characterized by obstetric and thrombotic
      complications in the presence of antiphospholipid antibodies. It can happen in an
      isolated way or in association with diffuse connective tissue diseases, mainly
      systemic lupus erythematosus. The association of APS with Takayasu arteritis (TA)
      is rarely described in the literature. We described a case of primary APS in a
      female patient who developed obstruction in large-size arteries, in spite of the
      use of oral anticoagulant, and increase of erythrocyte sedimentation rate,
      suggesting TA. The favorable response to prednisone treatment and later to
      infliximab reinforced the diagnosis of TA. The present report illustrates the
      existence of APS associated to TA, whose recognition is very important once the
      therapeutic strategy is radically different.

PMID- 16575492
TI  - A case of polyarteritis nodosa complicated by left central retinal artery
      occlusion, ischemic optic neuropathy, and retinal vasculitis.
AB  - A 23-year-old single female patient developed constitutional manifestations in
      the form of fever, weight loss, anorexia, malaise, fatigue, and generalized aches
      in January 1995, 2 weeks after an attack of German measles. This was followed by
      painful, reddish, macular skin lesions over both legs which healed by dark
      pigmentation (leucocytoclastic vasculitis), mononeuritis multiplex, and Raynaud's
      phenomena of both hands and feet. Angiography of lower limbs was done to
      visualize the arterial tree of both lower limbs and revealed typical beading of
      distal arterial branches, a diagnosis compatible with polyarteritis nodosa (PAN).
      At that time, the patient received prednisone (45 mg/day) and azatioprin (100
      mg/day) and responded well to treatment. In a second presentation in June 2005,
      the patient developed sudden attack of loss of vision in her left eye.
      Ophthalmological examination of the patient revealed evidence of left central
      retinal artery occlusion, ischemic optic neuropathy. The patient received methyl
      prednisolone, 1 g IV infusion, daily infusion for three consecutive days followed
      by oral prednisolone, 30 mg/day. The patient received pulse cyclophosphamide IV
      infusion (0.6 g/m2) on the fourth day. One week after receiving therapy, the
      patient progressed from having light perception to counting of fingers from a
      distance of 1 m.

PMID- 16575493
TI  - Hemophagocytic syndrome as one of main manifestations in untreated systemic lupus
      erythematosus: two case reports and literature review.
AB  - Hemophagocytic syndrome (HPS) is an unusual but fatal disorder characterized by
      pancytopenia and activation of macrophages. We describe two cases of untreated
      systemic lupus erythematosus (SLE) with HPS that presented as one of the
      manifestations of SLE. The onset of HPS was after parturition for one patient,
      and after abortion for the other. Bone marrow examination revealed severe
      hemophagocytosis in both patients. One patient responded to pulsed
      methylprednisone alone, and the other responded to pulsed methylprednisone plus
      intravenous immunoglobulin (IVIG). We believe accurate diagnosis, intensive
      therapy, and sufficient supportive cares are essential in improving patients'
      prognosis.

PMID- 16575494
TI  - The effect of calcitonin on beta-endorphin levels in postmenopausal osteoporotic
      patients with back pain.
AB  - The purpose of this study was to evaluate the efficacy of calcitonin on beta
      endorphin levels in female patients experiencing back pain associated with
      postmenopausal osteoporosis. The secondary purpose was to assess the pain and
      quality of life in these patients. There were 30 patients with a mean age of
      58.2+/-5.4 years in the treatment group and 26 patients with a mean age of 58.8+/
      5.2 years in the placebo group in this randomized, placebo-controlled study. The
      patients subcutaneously received 100 IU salmon calcitonin or placebo injections
      and 1,000 mg elementary calcium for 2 weeks. Baseline plasma beta-endorphin
      levels were measured and repeated after 2 weeks. Patients' pain and quality of
      life (QOL) were evaluated by using the Visual Analogue Scale, Modified Face
      Scale, Beck Depression Index, and Nottingham Health Profile. Patients' global
      assessment of disease activity was also performed at baseline and at the end of
      the first and second week. We found that plasma beta-endorphin levels in the
      treatment group were significantly higher than the placebo group at the end of
      the second week (p<0.001). Although pain and QOL scores were improved at the end
      of the second week in both groups (p<0.05), the improvement in the treatment
      group was more significant when compared with the placebo group (p<0.05).
      Therefore, calcitonin is an analgesic agent, as it increases the plasma beta
      endorphin levels in patients with postmenopausal osteoporosis, which consequently
      improves QOL.

PMID- 16575495
TI  - Severe acute hepatitis related to hydroxychloroquine in a woman with mixed
      connective tissue disease.
AB  - Antimalarial drugs are used for the control of mild manifestations of autoimmune
      diseases due to their low toxicity. Hydroxychloroquine (HCQ), a alpha
      hydroxylated derivative of chloroquine, is usually preferred because of its
      higher tolerability. Mild and unspecific gastrointestinal symptoms are the main
      secondary effects related to HCQ use. Less than 1% of subjects show liver enzyme
      increase, although the percentage can be as high as 50% in subjects with chronic
      liver disease. A woman with mixed connective tissue disease who developed a
      reversible acute hepatitis shortly after the initiation of low-dose HCQ is
      presented. Two previous cases of patients with acute liver failure have
      previously been published. All three cases have been reported in the absence of
      previous liver disease. It seems to be a dose-dependent, idiosyncratic, and
      molecule-specific toxic effect and must be considered, taking into account the
      potential bad prognosis.

PMID- 16575496
TI  - Effect of soy- and whey protein-isolate supplemented diet on the redox parameters
      of trained mice.
AB  - BACKGROUND: A number of clinical trials have successfully been performed using
      whey and/or soy proteins in the treatment of many diseases. They both have
      antioxidant properties, which appears to be a factor in aerobic physical
      performance as well. In addition, these are the most often used supplements that
      sportsmen take to increase their performance. AIM OF THE STUDY: To investigate
      the effect of whey and soy protein supplementation on redox parameters in the
      muscle, on body weight, and body composition in swimming-trained and non-trained
      animals. METHODS: The effect of whey and soy protein-isolate supplementation on
      muscle redox parameters, body weight, and body composition in trained and non
      trained mice was investigated after a single exhaustive bout of exercise. Steady
      state free radical concentration measured using electron spin resonance (ESR)
      spectroscopy, reduced and oxidized glutathione ratio, thiobarbituric acid
      reactive substances (TBARS), and protein carbonyl levels of the red leg muscle
      were measured. RESULTS: Free radical concentrations and glutathione composition
      of the tissue indicated that whey protein supplementation of the regular diet was
      able to prevent oxidative stress regardless of training. Soy protein
      supplementation decreased TBARS only in the muscle of untrained animals, while
      training per se lowered protein damage in all investigated groups. A mixture of
      soy and whey protein supplementation resulted in leaner animals after training,
      but had no synergistic effect on either of the measured redox parameters.
      CONCLUSIONS: Athletes consuming these supplements could train with higher
      exercise intensity. The antioxidant effect of the two proteins is based on
      different mechanisms of action.

PMID- 16575497
TI  - Inferior vena cava duplication and deep venous thrombosis.

PMID- 16575498
TI  - Pharmacokinetic consequences of active drug efflux at the blood-brain barrier.
AB  - PURPOSE: The objective of this simulation study was to investigate how the
      nature, location, and capacity of the efflux processes in relation to the
      permeability properties influence brain concentrations. METHODS: Reduced brain
      concentrations can be due to either influx hindrance, a gatekeeper function in
      the luminal membrane, which has been suggested for ABCB1 (P-glycoprotein), or
      efflux enhancement by transporters that pick up molecules on one side of the
      luminal or abluminal membrane and release them on the other side. Pharmacokinetic
      models including passive transport, influx hindrance, and efflux enhancement were
      built using the computer program MATLAB. The simulations were based on
      experimentally obtained parameters for morphine, morphine-3-glucuronide, morphine
      6-glucuronide, and gabapentin. RESULTS: The influx hindrance process is the more
      effective for keeping brain concentrations low. Efflux enhancement decreases the
      half-life of the drug in the brain, whereas with influx hindrance the half-life
      is similar to that seen with passive transport. The relationship between the
      influx and efflux of the drug across the blood-brain barrier determines the
      steady-state ratio of brain to plasma concentrations of unbound drug, K(p,uu).
      CONCLUSIONS: Both poorly and highly permeable drugs can reach the same steady
      state ratio, although the time to reach steady state will differ. The volume of
      distribution of unbound drug in the brain does not influence K(p,uu), but does
      influence the total brain-to-blood ratio K(p) and the time to reach steady state
      in the brain.

PMID- 16575499
TI  - Molecular mobility in glass forming fananserine: a dielectric, NMR, and TMDSC
      investigation.
AB  - PURPOSE: This study was conducted to characterize the molecular mobility of
      supercooled fananserine and derive from this analysis the non-Arrhenius and
      nonexponential properties of the primary alpha-relaxation. METHODS: The use of
      three investigation techniques of the molecular mobility, namely, dielectric
      relaxation, modulated differential scanning calorimetry, and proton nuclear
      magnetic resonance, allowed us to describe the dynamic properties of supercooled
      fananserine on a wide range of frequencies and temperatures, ranging from the
      melting temperature T(m) = 372 K down to the glass transition temperature T(g) =
      292 K. RESULTS: We emphasized the capacity of these three techniques to give a
      coherent set of information. We used the coupling-model theory to interpret the
      dielectric results. It allowed us to identify two relaxation processes (alpha and
      beta), corresponding to different molecular motions. The temperature evolution of
      the alpha-relaxation indicates that fananserine is a fragile glass former, as
      reflected by the steepness index value, m = 77. The temperature T(o) where the
      relaxation times diverge was also determined. CONCLUSIONS: The description of the
      dielectric relaxation data in terms of the Kohlrausch-Williams-Watt relaxation
      function has shown the existence of an additional low-amplitude relaxation
      process assigned to the so-called Johari-Goldstein process. Mainly concerned by
      the primary alpha-process directly involved in the glass formation, we derived
      from this analysis the characteristic features of this process and showed that
      supercooled fananserine is characterized by a strongly non-Arrhenius and
      nonexponential behavior.

PMID- 16575500
TI  - Crystalline form information from multiwell plate salt screening by use of Raman
      microscopy.
AB  - PURPOSE: The purpose of this study was to establish a useful methodology,
      possibly providing information on the stoichiometry of pharmaceutical drug salts
      obtained from salt screening by using a multiwell plate and a Raman microscope.
      METHODS: Tamoxifen salt screening was conducted with monobasic and polybasic
      acids on 96-well quartz plates with a Raman microscope. Appearance and
      crystalline forms of salts prepared on 96-well plates were observed by polarizing
      light microscope and Raman microscope, respectively. Based on the results of the
      salt screening, tamoxifen citrate and fumarate salts were prepared on a large
      scale. The salts prepared were characterized by powder X-ray diffractometry
      (PXRD) and ion chromatography. RESULTS: The results of the multiwell salt
      screening indicated that tamoxifen has a tendency toward the formation of mono
      salt as opposed to hemi salt with polybasic acid, and that most of tamoxifen
      salts gave several potential polymorphic forms. PXRD patterns of scaled-up
      tamoxifen citrate and fumarate salts suggested that the same crystalline form was
      obtained from the binary mixture regardless of molar ratios of 2:1 or 1:1
      (tamoxifen/acid). The crystalline forms obtained were tamoxifen monocitrate and
      monofumarate salts as measured by ion chromatography. CONCLUSIONS: Salt screening
      on multiwell plates with a Raman microscope provided novel insight into the
      characteristics prediction of the stoichiometrical salts in addition to potential
      polymorph information. Based on the stoichiometrical information of salts, the
      amount of compound and time required for crystalline form selection of drug
      candidates would be significantly reduced.

PMID- 16575501
TI  - Understanding clinical trials in migraine.
AB  - The following points are covered in this review. (1) How a randomised clinical
      trial in migraine is performed. The whole process from idea to publication of an
      article is reviewed. (2) How to understand a paper on clinical trials in
      migraine. The aim of the study, design of study, efficacy measures and
      presentation of results are reviewed. The aim of the study is often stated
      vaguely and it is suggested to look at the power calculations in order to
      understand the aim of the study. The aims and the results of the trial programmes
      of the triptans are reviewed. Results of the study should be presented with
      95%CI. (3) How to understand meta-analyses in migraine. Relationship between meta
      analyses and head-to-head comparative trials is reviewed; and it is concluded
      that head-to-head comparisons remain the "golden standard" with meta-analyses as
      a useful supplement.

PMID- 16575502
TI  - Diagnosing cervicogenic headache.
AB  - The notion that disorders of the cervical spine can cause headache is more than a
      century old, yet there is still a great deal of debate about cervicogenic
      headache (CEH) in terms of its underlying mechanisms, its signs and symptoms, and
      the most appropriate treatments for it. CEH is typically a unilateral headache
      that can be provoked by neck movement, awkward head positions or pressure on
      tender points in the neck. The headaches can last hours or days, and the pain is
      usually described as either dull or piercing. Convergence of the upper cervical
      roots on the nucleus caudalis of the trigeminal tract is the most commonly
      accepted neurophysiological explanation for CEH. In most cases, CEH is caused by
      pathology in the upper aspect of the cervical spine, but the type and exact
      location of the pathology varies substantially among individual cases.
      Anaesthetic blocks may be necessary to confirm the diagnosis of CEH, showing that
      the source of pain is in the neck. Differential diagnosis is sometimes a
      challenge because CEH can be mistaken for other forms of unilateral headache,
      especially unilateral migraine without aura. Neuroimaging and kinematic analysis
      of neck motion may aid in diagnosing difficult CEH.

PMID- 16575503
TI  - Headache epidemiology: how and why?
AB  - The objective is to give an introduction to methods and study designs used in
      headache epidemiologic studies, to discuss their merits and problems, and to show
      the potential of such studies. The distinction between descriptive and analytic
      studies is made, and methodological issues are discussed related to headache case
      definition, validation of diagnoses, time frame for headache, instruments for
      data collection, source population and sampling methods, as well as the problems
      with bias and confounding. Examples of how different designs (case series,
      ecological, cross-sectional, case-control and cohort studies) have been used in
      the headache field are then presented. Studies on headache epidemiology are
      important to document the prevalence and burden of headache disorders. It is as
      important that studies with an analytical design can prove to be potent tools to
      disclose causes and risk factors for headache, but a standardisation of methods
      is needed to increase comparability of studies.

PMID- 16575504
TI  - The history of the migraine trust.
AB  - The history of a medical charity founded for the purpose of initiating research
      into the commonest of all human afflictions-headache. Of the 100 causes, migraine
      is one of the commonest, and in spite of the lack of interest of the medical
      profession, this review shows how the pace of research rapidly increased as
      evidenced by the biennial International Symposia of the Migraine Trust.

PMID- 16575505
TI  - Salivary cortisol, dehydroepiandrosterone-sulphate (DHEA-S) and testosterone in
      women with chronic migraine.
AB  - Hypothalamus-pituitary-adrenal (HPA) axis activity was monitored in 20 women with
      chronic migraine (CM), previously affected by medication overuse headache (MOH),
      in comparison to healthy women (20 subjects) by measuring salivary cortisol,
      testosterone, dehydroepiandrosterone-sulphate (DHEA-S) levels, and their ratios,
      one week after the end of the MOH rehabilitation procedure. The participants were
      instructed how to collect saliva samples at home, a procedure that was performed
      twice a day (08:00 a.m. and 8:00 p.m.). Morning and evening levels of cortisol
      were significantly increased in CM patients with respect to controls. With regard
      to the cortisol/DHEA-S ratio, an inverse marker of psycho-physical wellbeing, CM
      women showed significantly higher values than controls. Moreover,
      testosterone/cortisol ratios (anabolic/catabolic index of physical performance)
      were significantly lower in CM patients than in controls. In the present study,
      CM appears not to be associated with an impairment of cortisol and DHEAS
      circadian fluctuation; however, CM patients present alterations in HPA axis
      function that might contribute to metabolic and psychological alterations that
      have also been associated with CM.

PMID- 16575506
TI  - Moving into the ranks of the world's important journals.

PMID- 16575509
TI  - Series introduction:Molecular morphological approaches to the pathophysiology of
      liver disease.

PMID- 16575508
TI  - New trends of immunohistochemistry for making differential diagnosis of breast
      lesions.
AB  - Immunohistochemistry is widely used for pathological diagnosis of breast lesions.
      Other than hormone receptors and HER2/neu analysis for primary breast carcinomas,
      several markers may be useful for differential diagnoses, although in limited
      situations. To decide the malignant potential of intraductal proliferative
      lesions, analysis for the staining pattern of cytokeratins may be a good
      reference. Most ductal carcinoma in situ cases are diffusely positive for luminal
      cell markers (CK8, CK18, CK19), but negative for basal cell markers (CK5/6 and
      CK14). However, usual ductal hyperplasia may show the mosaic staining patterns
      for any of these markers, which may indicate a heterogeneous cell population in
      benign lesions. Myoepithelial markers (alpha-SMA, myosin, calponin, p63, CD10)
      are almost consistently positive for benign papillomas but they do not completely
      distinguish intraductal papillary carcinomas. Preservation of myoepithelial layer
      is the diagnostic key when looking at benign sclerosing lesions, including
      carcinoma with pseudoinvasive structures. E-cadherin is mostly positive for
      ductal carcinomas but negative for lobular carcinomas. Some of the lobular
      carcinomas are positive for 34betaE12, but they are consistently negative for
      CK5/6. Comparison with histopathological findings of hematoxylin and eosin is
      essential to make proper diagnosis in the individual case.

PMID- 16575507
TI  - Role of macula densa neuronal nitric oxide synthase in renal diseases.
AB  - Macula densa cells have an important role in the regulation of glomerular blood
      flow and glomerular filtration by its regulation of afferent arteriolar vascular
      tone. Nitric oxide derived from neuronal nitric oxide synthase (nNOS) in macula
      densa can dilate afferent arterioles. Macula densa nNOS is important for renin
      secretion, and its expression is regulated by dietary salt, renal angiotensin II,
      intracellular pH, and other factors. In salt-sensitive hypertension, nNOS is
      suppressed, whereas in SHR or in the early phase of diabetes, nNOS is increased
      in macula densa along with NADPH oxidase, which limits NO bioavailability. Renal
      damage induced by hypertension, diabetes, and hyperlipidemia could be prevented
      by enhancement of nNOS in macula densa with ACEI, dipyridamole, alpha(1)-receptor
      blocker, a low-salt diet, or sodium bicarbonate. Sodium bicarbonate is a safe and
      clinically available enhancer of nNOS in macula densa that increases glomerular
      blood flow and prevents the reduction of GFR in radiocontrast nephropathy and
      chronic renal failure. In conclusion, the enhancement of nNOS in the macula densa
      can be a promising strategy to prevent reduction of renal function.

PMID- 16575510
TI  - Angiogenic cell therapy for hepatic fibrosis.
AB  - Progression of liver fibrosis has been linked with injuries associated with
      hypoxia and neovascularization. Neovascularization consists of angiogenesis and
      vasculogenesis, representing formation of blood vessels by differentiation of
      endothelial progenitor cells (EPCs). We investigated antifibrogenic and
      regenerative effects of EPC transplantation in chronic liver injury. Rat EPCs
      were isolated from bone marrow cells and examined in vitro for lineage markers.
      Recipient rats were injected intraperitoneally with dimethylnitrosamine (DMN)
      three times weekly for 4 weeks, plus EPC transplantation once weekly for 4 weeks.
      Transplanted rats showed suppression of liver fibrogenesis. Expression of growth
      factors promoting liver regeneration such as hepatocyte growth factor (HGF),
      transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), and
      vascular endothelial growth factor (VEGF) was increased in transplanted rats,
      together with hepatocyte proliferation. Normal liver function parameters such as
      transaminase, total bilirubin, total protein, and albumin were maintained in
      transplanted rats. EPC transplantation is effective not only for preventing liver
      fibrosis but also for promoting regeneration in chronically damaged livers. Also,
      recently it has been reported that green fluorescent protein-positive bone marrow
      cells contribute to the liver tissue repair of fibrosis model rats. EPC
      transplantation might become an alternative if further preclinical investigation
      finds it to be effective in severely cirrhotic livers.

PMID- 16575511
TI  - Studies on oxidative stress in liver diseases: important future trends in liver
      research.
AB  - Oxidative stress has recently been shown to play an important role in various
      liver diseases. Therefore, further studies on oxidative stress in liver diseases
      are urgently required. In this review, oxidative stress is discussed from the
      aspects of molecular morphology, metabolism, and aging.

PMID- 16575512
TI  - Perineuronal germinal cells in the rat cerebral cortex.
AB  - The generation and renewal of cells in the adult mammalian central nervous system
      maintains brain functions, including plasticity. Even in the cerebral cortex of
      adult mammals, glial cells are thought to be replaced with newly generated cells
      every 100 days. Recently, we demonstrated that this proliferation is stimulated
      by neural activity. However, whether any germinal areas exist in the cortical
      parenchyma is unknown. Here, we examined the proliferating cell dynamics in the
      cerebral cortex of adult rats using BrdU labeling and immunohistochemistry for
      NeuN and lamin B1. At 2 h after a single injection of BrdU, more than 80% of BrdU
      labeled cells were observed in the perineuronal territory in which the BrdU
      labeled nuclei were located within 5 microm from neuronal nuclei. The ratio of
      perineuronal cells to nonperineuronal cells in BrdU-labeled cells gradually
      decreased over the 2 weeks following BrdU injection. These observations indicate
      that numerous cortical cells proliferate in the perineuronal territory, the
      germinal soil, and that part of these newly generated cells migrate from the
      perineuronal territory into the surrounding areas during the 2 weeks following
      mitosis.

PMID- 16575513
TI  - Vascularization in tissue remodeling after rat hepatic necrosis induced by
      dimethylnitrosamine.
AB  - We observed postnecrotic tissue remodeling to examine vascularization in adult
      rat livers. Livers, bone marrow, and peripheral blood from rats at 24 h to 14
      days after an injection of dimethylnitrosamine (DMN) were examined by light
      microscopic, immunohistochemical, and ultrastructural methods. Numerous ED-1 (a
      marker for rat monocytes/macrophages)-positive round mononuclear cells
      infiltrated in the necrotic areas at 36 h after DMN treatment. On day 5, when
      necrotic tissues were removed, some of the cells were transformed from round to
      spindle in shape. On day 7, these cells were contacted with residual reticulin
      fibers and became positive for SE-1, a marker of hepatic sinusoidal endothelial
      cells and Tie-1, an endothelial cell-specific surface receptor, associated with
      frequent occurrence of ED-1/SE-1 and ED-1/Tie-1 double-positive spindle cells.
      Ultrastructurally, the spindle cells simultaneously showed phagocytosis and
      endothelial cell-like morphology. With time necrotic areas diminished, and on day
      14, the necrotic tissues were almost replaced by regenerated liver tissues and
      thin bundles of central-to-central bridging fibrosis. Bone marrow from 12 h to
      day 2 showed an increase of BrdU-positive mononuclear cells. Some of them were
      positive for ED-1. The BrdU-labeled and ED-1-positive cells appeared as early as
      12 h after DMN injection and reached a peak in number at 36 h. They were similar
      in structure to ED-1-positive cells in necrotic liver tissues. These findings
      suggest that round mononuclear ED-1-positive cells proliferate first in bone
      marrow after DMN treatment, reach necrotic areas of the liver through the
      circulation, and differentiate to sinusoidal endothelial cells. Namely, hepatic
      sinusoids in DMN-induced necrotic areas may partly be reorganized possibly by
      vasculogenesis.

PMID- 16575515
TI  - An autopsy case of primary mixed choriocarcinoma and mature teratoma located in
      the thymic region associated with elevated human chorionic gonadotropin levels
      and characteristic testicular changes.
AB  - An autopsy case of a 19-year-old male Japanese student with a primary mixed
      choriocarcinoma and mature teratoma in the thymic region is reported. The patient
      died 7 days after he first noticed fever and dyspnea. On autopsy, an anterior
      mediastinal mass was found to be in contact with the thymic gland. The mass
      weighed 270 g and measured 12.5 cm x 10 cm x 5 cm. The left thoracic cavity
      contained 2200 ml bloody pleural effusion and 200 g coagula due to hemorrhage
      from the tumor. Metastasized choriocarcinoma was seen in both lungs and the
      liver. High serum levels of human chorionic gonadotropin (HCG, 1 634 000 mIU/ml)
      and a decreased weight of the testes (2.0 g each) with Leydig cell
      hyperplasia/hypertrophy and the seminiferous tubules with hyaline ghost tubules
      or Sertoli cell only tubules were seen; other male reproductive organs were
      histologically normal. Although the serum testosterone level was within the
      normal range (5.75 ng/ml), luteinizing hormone (LH, 0.1 mIU/ml) and follicle
      stimulating hormone (FSH, 0.3 mIU/ml) levels were decreased. High serum levels of
      HCG and characteristic testicular changes are drscribed.

PMID- 16575516
TI  - Biography of Professor Jose A. Cabezas.

PMID- 16575514
TI  - Bicarbonate secretion by rat bile duct brush cells indicated by
      immunohistochemical localization of CFTR, anion exchanger AE2, Na+/HCO3 
      cotransporter, carbonic anhydrase II, Na+/H+ exchangers NHE1 and NHE3, H+/K+
      ATPase, and Na+/K+-ATPase.
AB  - The function of brush cells (BCs) is unknown. In a previous study, the rat common
      bile duct was examined by ultrastructural cytochemical methods for localizing
      HCO(3) (-), Cl(-), and Na(+) ions. All ion precipitates increased in or on BCs
      after secretin or meal stimulation, and it was proposed that BCs may secrete
      NaHCO(3). In this study, immunohistochemical localization of proteins known to be
      important in HCO(3) (-) secretion was investigated in the rat common bile duct.
      Immunoreactivity of proteins involved in Cl(-)/HCO(3) (-) exchange reaction,
      cystic fibrosis transmembrane conductance regulator (CFTR) and Cl(-)/HCO(3) (-)
      exchanger (AE2), was found on the microvilli (MV) and along the basolateral
      membrane (BLM) of BCs. The proteins involved in HCO(3) (-) production,
      Na(+)/HCO(3) (-) cotransporter (NBC), was found along the BLM but was absent on
      the MV, whereas carbonic anhydrase II (CA II) was observed on the MV and along
      the BLM. Of proteins responsible for the extrusion of H(+), Na(+)/H(+) exchanger
      1 (NHE1) was localized along the BLM whereas Na(+)/H(+) exchanger 3 (NHE3) was
      found on the MV and BLM. Activity of H(+)/K(+)-ATPase was found along the BLM and
      on the MV, and Na(+)/K(+)-ATPase was localized along the BLM. The
      immunoreactivity of most of these proteins was absent or weak in principal cells.
      These results strongly suggest that BCs are a significant source of HCO(3) (-)
      secretion.

PMID- 16575517
TI  - Special issue: Viruses and sialic acids. Dedicated to Professor Jose A. Cabezas.

PMID- 16575519
TI  - The role of sialic acid in human polyomavirus infections.
AB  - JC virus (JCV) and BK virus (BKV) are human polyomaviruses that infect
      approximately 85% of the population worldwide [1,2]. JCV is the underlying cause
      of the fatal demyelinating disease, progressive multifocal leukoencephalopathy
      (PML), a condition resulting from JCV induced lytic destruction of myelin
      producing oligodendrocytes in the brain [3]. BKV infection of kidneys in renal
      transplant recipients results in a gradual loss of graft function known as
      polyomavirus associated nephropathy (PVN) [4]. Following the identification of
      these viruses as the etiological agents of disease, there has been greater
      interest in understanding the basic biology of these human pathogens [5,6].
      Recent advances in the field have shown that viral entry of both JCV and BKV is
      dependent on the ability to interact with sialic acid. This review focuses on
      what is known about the human polyomaviruses and the role that sialic acid plays
      in determining viral tropism.

PMID- 16575518
TI  - Role of sialic acid-containing molecules in paramyxovirus entry into the host
      cell: a minireview.
AB  - Sialic acid-containing compounds play a key role in the initial steps of the
      paramyxovirus life cycle. As enveloped viruses, their entry into the host cell
      consists of two main events: binding to the host cell and membrane fusion. Virus
      adsorption occurs at the surface of the host cell with the recognition of
      specific receptor molecules located at the cell membrane by specific viral
      attachment proteins. The viral attachment protein present in some paramyxoviruses
      (Respirovirus, Rubulavirus and Avulavirus) is the HN glycoprotein, which binds to
      cellular sialic acid-containing molecules and exhibits sialidase and fusion
      promotion activities. Gangliosides of the gangliotetraose series bearing the
      sialic acid N-acetylneuraminic (Neu5Ac) on the terminal galactose attached in
      alpha2-3 linkage, such as GD1a, GT1b, and GQ1b, and neolacto-series gangliosides
      are the major receptors for Sendai virus. Much less is known about the receptors
      for other paramyxoviruses than for Sendai virus. Human parainfluenza viruses 1
      and 3 preferentially recognize oligosaccharides containing N
      acetyllactosaminoglycan branches with terminal Neu5Acalpha2-3Gal. In the case of
      Newcastle disease virus, has been reported the absence of a specific pattern of
      the gangliosides that interact with the virus. Additionally, several works have
      described the use of sialylated glycoproteins as paramyxovirus receptors.
      Accordingly, the design of specific sialic acid analogs to inhibit the sialidase
      and/or receptor binding activity of viral attachment proteins is an important
      antiviral strategy. In spite of all these data, the exact nature of paramyxovirus
      receptors, apart from their sialylated nature, and the mechanism(s) of viral
      attachment to the cell surface are poorly understood.

PMID- 16575520
TI  - Role of sialic acids in rotavirus infection.
AB  - Rotaviruses are the leading cause of childhood diarrhea. The entry of rotaviruses
      into the host cell is a complex process that includes several interactions of the
      outer layer proteins of the virus with different cell surface molecules. The fact
      that neuraminidase treatment of the cells, or preincubation of the virus with
      sialic acid-containing compounds decrease the infectivity of some rotavirus
      strains, suggested that these viruses interact with sialic acid on the cell
      surface. The infectivity of some other rotavirus strains is not affected by
      neuraminidase treatment of the cells, and therefore they are considered
      neuraminidase-resistant. However, the current evidence suggests that even these
      neuraminidase-resistant strains might interact with sialic acids located in
      context different from that of the sialic acids used by the neuraminidase
      sensitive strains. This review summarizes our current knowledge of the rotavirus
      sialic acid interaction, its structural basis, the specificity with which
      distinct rotavirus isolates interact with sialic acid-containing compounds, and
      also the potential use of these compounds as therapeutic agents.

PMID- 16575521
TI  - Differential usage of carbohydrate co-receptors influences cellular tropism of
      Theiler's murine encephalomyelitis virus infection of the central nervous system.
AB  - Theiler's murine encephalomyelitis viruses (TMEV) are ubiquitous pathogens of
      mice, producing either rapidly fatal encephalitis (high-neurovirulence strains)
      or persistent central nervous system infection and inflammatory demyelination
      (low-neurovirulence strains). Although a protein entry receptor has not yet been
      identified, carbohydrate co-receptors that effect docking and concentration of
      the virus on the cell surface are known for both TMEV neurovirulence groups. Low
      neurovirulence TMEV use alpha2,3-linked N-acetylneuramic acid (sialic acid) on an
      N-linked glycoprotein, whereas high-neurovirulence TMEV use the proteoglycan
      heparan sulfate (HS) as a co-receptor. While the binding of low-neurovirulence
      TMEV to sialic acid can be inhibited completely, only a third of the binding of
      high-neurovirulence TMEV to HS is inhibitable, suggesting that high
      neurovirulence strains use another co-receptor or bind directly to the putative
      protein entry receptor. Four amino acids on the surface (VP2 puff B) of low
      neurovirulence strains make contact with sialic acid through non-covalent
      hydrogen bonds. Since these virus residues are conserved in all TMEV strains, the
      capsid conformation of this region is probably responsible for sialic acid
      binding. A persistence determinant that maps within the virus coat using
      recombinant TMEV is also conformational in nature. Low-neurovirulence virus
      variants that do not bind to sialic acid fail to persist in the central nervous
      system of mice, indicating a role for sialic acid binding in TMEV persistence.
      Analysis of high-neurovirulence variants that do not bind HS demonstrates that HS
      co-receptor usage influences neuronal tropism in brain, whereas, the HS co
      receptor use is not required for the infection of spinal cord anterior horn cells
      associated with poliomyelitis.

PMID- 16575522
TI  - Sialic acids as receptor determinants for coronaviruses.
AB  - Among coronaviruses, several members are able to interact with sialic acids. For
      bovine coronavirus (BCoV) and related viruses, binding to cell surface components
      containing N-acetyl-9- O-acetylneuraminic acid is essential for initiation of an
      infection. These viruses resemble influenza C viruses because they share not only
      the receptor determinant, but also the presence of an acetylesterase that
      releases the 9- O-acetyl group from sialic acid and thus abolishes the ability of
      the respective sialoglycoconjugate to function as a receptor for BCoV. As in the
      case of influenza viruses, the receptor-destroying enzyme of BCoV is believed to
      facilitate the spread of virus infection by removing receptor determinants from
      the surface of infected cells and by preventing the formation of virus
      aggregates. Another coronavirus, porcine transmissible gastroenteritis virus
      (TGEV) preferentially recognizes N-glycolylneuraminic acid. TGEV does not contain
      a receptor-destroying enzyme and does not depend on the sialic acid binding
      activity for infection of cultured cells. However, binding to sialic acids is
      required for the enteropathogenicity of TGEV. Interaction with
      sialoglycoconjugates may help the virus to pass through the sialic acid-rich
      mucus layer that covers the viral target cells in the epithelium of the small
      intestine. We discuss that the BCoV group of viruses may have evolved from a TGEV
      like ancestor by acquiring an acetylesterase gene through heterologous
      recombination.

PMID- 16575523
TI  - Structure, function and evolution of the hemagglutinin-esterase proteins of
      corona- and toroviruses.
AB  - Virus attachment to host cells is mediated by dedicated virion proteins, which
      specifically recognize one or, at most, a limited number of cell surface
      molecules. Receptor binding often involves protein-protein interactions, but
      carbohydrates may serve as receptor determinants as well. In fact, many different
      viruses use members of the sialic acid family either as their main receptor or as
      an initial attachment factor. Sialic acids (Sias) are 9-carbon negatively-charged
      monosaccharides commonly occurring as terminal residues of glycoconjugates. They
      come in a large variety and are differentially expressed in cells and tissues. By
      targeting specific Sia subtypes, viruses achieve host cell selectivity, but only
      to a certain extent. The Sia of choice might still be abundantly present on non
      cell associated molecules, on non-target cells (including cells already infected)
      and even on virus particles themselves. This poses a hazard, as high-affinity
      virion binding to any of such "false'' receptors would result in loss of
      infectivity. Some enveloped RNA viruses deal with this problem by encoding virion
      associated receptor-destroying enzymes (RDEs). These enzymes make the attachment
      to Sia reversible, thus providing the virus with an escape ticket. RDEs occur in
      two types: neuraminidases and sialate-O-acetylesterases. The latter, originally
      discovered in influenza C virus, are also found in certain nidoviruses, namely in
      group 2 coronaviruses and in toroviruses, as well as in infectious salmon anemia
      virus, an orthomyxovirus of teleosts. Here, the structure, function and evolution
      of viral sialate-O-acetylesterases is reviewed with main focus on the
      hemagglutinin-esterases of nidoviruses.

PMID- 16575525
TI  - Avian and human receptor binding by hemagglutinins of influenza A viruses.
AB  - An understanding of the structural determinants and molecular mechanisms involved
      in influenza A virus binding to human cell receptors is central to the
      identification of viruses that pose a pandemic threat. To date, only a limited
      number of viruses are known to have infected humans even sporadically, and this
      has recently included the virulent H5 and H7 avian viruses. We compare here the 3
      dimensional structures of H5 and H7 hemagglutinins (HA) complexed with avian and
      human receptor analogues, to highlight regions within the receptor binding
      domains of these HAs that might prevent strong binding to the human receptor.

PMID- 16575524
TI  - Localisation and distribution of O-acetylated N-acetylneuraminic acids, the
      endogenous substrates of the hemagglutinin-esterases of murine coronaviruses, in
      mouse tissue.
AB  - Infections by mouse hepatitis viruses result in disease of the liver, the
      gastrointestinal tract, respiratory tract, and the central nervous system.
      Coronaviruses related to mouse hepatitis virus express a hemagglutinin-esterase
      surface glycoprotein, which specifically hydrolyses either 5-N-acetyl-4-O-acetyl
      neuraminic acid (Neu4,5Ac(2)) or 5-N-acetyl-9-O-acetyl neuraminic acid
      (Neu5,9Ac(2)). Moreover, these sialic acids represent potential cellular receptor
      determinants for murine coronaviruses. Until now, the distribution of these
      sialic acids in mouse brain was not thoroughly investigated. Particularly
      Neu4,5Ac(2) was not yet found in mouse brain. Using a sensitive method of gas
      chromatography coupled to mass spectrometry in the electron impact mode of
      ionization this manuscript demonstrates the occurrence of 13 different sialic
      acids varying in their alkyl and acyl substituents in mouse tissues including 5-N
      acetyl-4-O-acetyl-9-O-lactyl-neuraminic acid (Neu4,5Ac(2)9Lt), 5-N-acetyl-9-O
      lactyl-neuraminic acid (Neu5Ac9Lt), 5-N-acetyl-8-O-methyl-neuraminic acid
      (Neu5Ac8Me) and the 1,7-lactone (Neu5Ac1,7L) of neuraminic acid. Neu4,5Ac(2),
      relatively abundant in the gut, was present as a minor compound in all tissues,
      including liver, olfactory lobe, telencephalon, metencephalon and hippocampus.
      Neu5,9Ac(2) was also found in these tissues, except in the liver. It is suggested
      that these sialic acids represent the endogenous substrate and receptor
      determinants for murine coronaviruses.

PMID- 16575526
TI  - Sequence analysis and receptor specificity of the hemagglutinin of a recent
      influenza H2N2 virus isolated from chicken in North America.
AB  - Influenza viruses bind host cells following an interaction between the viral
      hemagglutinin (HA) protein and host cell sialylated glycoproteins and
      glycolipids. Differences in binding affinities of the HAs for different types of
      sialic acid linkages (alpha2-3 vs. alpha2-6) contribute to determining the host
      range of an influenza virus. The ability of an avian influenza virus HA to bind
      the human form of the receptor may be one requirement for an avian virus to
      propagate in the human population. In this paper, we describe the
      characterization of the HA from an H2N2 virus isolated from a Pennsylvania
      chicken farm in 2004. Sequence analysis revealed that this HA is a member of the
      Eurasian clade, and receptor binding studies show that it maintains its
      specificity for the avian influenza virus alpha2-3 linked sialic acid receptor.

PMID- 16575527
TI  - Human trachea primary epithelial cells express both sialyl(alpha2-3)Gal receptor
      for human parainfluenza virus type 1 and avian influenza viruses, and
      sialyl(alpha2-6)Gal receptor for human influenza viruses.
AB  - We reported previously that the dominant receptors of influenza A and B viruses,
      and human and murine respiroviruses, were sialylglycoproteins and gangliosides
      containing monosialo-lactosamine type I-and II-residues, such as sialic acid
      alpha2-3(6)-Galbeta1-3(4)-GlcNAcbeta1-. In addition, the Siaalpha2-3Gal linkage
      was predominantly recognized by avian and horse influenza viruses, and human
      parainfluenza virus type 1 (hPIV-1), whereas the Siaalpha2-6Gal linkage was
      mainly recognized by human influenza viruses (Paulson JC in "The Receptors''
      [Conn M Ed] 2, 131-219 (1985); Suzuki Y, Prog Lipid Res 33, 429-57 (1994); Ito T,
      J Virol 73, 6743-51 (2000); Suzuki Y, J Virol 74, 11825-31 (2000); Suzuki T, J.
      Virol 75, 4604-4613 (2001); Suzuki Y, Biol. Pharm. Bull. 28, 399-408 (2005)). To
      clarify the distribution of influenza virus receptors on the human bronchial
      epithelium cell surface, we investigated a primary culture of normal human
      bronchial epithelial (NHBE) cells using two types of lectin (MAA and SNA), which
      recognize sialyl linkages (alpha2-3 and alpha2-6), using fluorescence-activated
      cell-sorting analysis. The results showed that both alpha2-3- and alpha2-6-linked
      Sias were expressed on the surface of primary human bronchial epithelial cells.
      The cells infected by hPIV-1 bound to MAA, confirming that cells targeted by hPIV
      1 have alpha2-3-linked oligosaccharides. We also compared the ability of hPIV-1
      and human influenza A virus to infect primary human bronchial epithelial cells
      pre-treated with Siaalpha2-3Gal-specific sialidase from Salmonella typhimurium.
      No difference was observed in the number of sialidase pre-treated and non-treated
      cells infected with human influenza A virus, which binds to Siaalpha2-6Gal-linked
      oligosaccharides. By contrast, the number of cells infected with hPIV-1 decreased
      significantly upon sialidase treatment. Thus, cultured NHBE cells showed both
      alpha2-3-linked Sias recognized by hPIV-1 and avian influenza virus receptors,
      and alpha2-6-linked Sias recognized by human influenza virus receptors.

PMID- 16575528
TI  - Gangliosides are not essential for influenza virus infection.
AB  - Sialic acid is known to be an essential part of influenza virus receptors, but
      the specific identity of the receptor molecules on target cells is still not
      defined. In particular, the relative roles played by cellular sialylglycoproteins
      and gangliosides in virus entry into target cells remain unclear. To test whether
      gangliosides are essential for virus infection, we used the GM-95 mutant cell
      line of mouse B16 melanoma which lacks synthesis of major glycosphingolipids
      including gangliosides. We found that GM-95 cells grown in serum-containing
      medium harboured substantial amounts of ganglioside receptors for influenza virus
      due to incorporation of serum gangliosides. To obtain ganglioside-free cells, we
      adapted GM-95 cells to growth in defined serum-free (sf) medium. Ganglioside-free
      GM-95-sf cells could be infected by avian and human influenza A viruses and
      produced infectious virus progeny demonstrating that gangliosides were neither
      absolutely necessary for the early nor for the late stages of the infection.
      However, sensitivity of the GM-95-sf cells to the viruses was 2-4 times lower
      than that of the ganglioside-containing parent cell line. Further studies are
      needed to specify whether this effect was due to the lack of gangliosides,
      neutral glycosphingolipids, or other effects.

PMID- 16575530
TI  - Unsaturated N-acetyl- D-glucosaminuronic acid glycosides as inhibitors of
      influenza virus sialidase.
AB  - The threat of pandemic influenza is a significant concern of governments
      worldwide. There is a very limited and relatively expensive armament to tackle
      such a pandemic should it occur. This fact provides much impetus to the
      scientific community for the discovery of new and less expensive anti-influenza
      drugs. Our longstanding interest in the inhibition of influenza virus sialidase,
      coupled with the development of simple carbohydrates that mimic an unsaturated
      derivative of the enzyme's naturally-occurring ligand, N-acetylneuraminic acid,
      has led us to investigate the development of influenza virus sialidase inhibitors
      based on these mimetics. We have successfully prepared a range of these
      compounds, in good yield, from the relatively inexpensive carbohydrate N
      acetylglucosamine utilising a short synthetic procedure. We have employed a
      sialidase inhibition assay for biological evaluation of the target compounds and
      to our delight these mimetics have displayed significant inhibition of influenza
      virus sialidase.

PMID- 16575529
TI  - Search for additional influenza virus to cell interactions.
AB  - Sialyl oligosaccharides have long been considered to be the sole receptors for
      influenza virus. However, according to [1] some viruses are able to grow in
      sialic-free MDCK cells. Here we attempted to reveal a possible second, non-sialic
      receptor, hypothesizing the involvement of additional carbohydrate lectin
      recognition in influenza virus reception process, first of all in situations when
      a lectin of the host cell could recognize the viral carbohydrate ligand. We
      tested the presence of galactose- and sialic acid-binding lectins, as well as
      mannoside- and sulfo-N-acetyllactosamine-recognizing properties of MDCK and Vero
      cells using polyacrylamide neoglycoconjugates and antibodies. MDCK cells bind
      galactoside probes stronger than Vero cells, whereas Vero cells bind
      preferentially sialoside, mannoside and various sulfo-oligosaccharide probes. The
      probing of viruses with the neoglycoconjugates revealed specific 6'-HSO (3)
      LacNAc (but not other sulfated oligosaccharides) binding property of A and B
      human strains. Affinity of 6'-HSO (3) LacNAc probe was comparable with affinity
      of 6'-SiaLac probe but the binding was not inhibited by the sialooligosaccharide.

PMID- 16575531
TI  - Structural analysis of a designed inhibitor complexed with the hemagglutinin
      neuraminidase of Newcastle disease virus.
AB  - Viruses of the Paramyxoviridae family are the leading cause of respiratory
      disease in children. The human parainfluenza viruses (hPIV) are members of the
      Paramyxovirinae subfamily, which also includes mumps virus, Newcastle disease
      virus (NDV), Sendai virus (SV) and simian type 5 virus (SV5). On the surface of
      these viruses is the glycoprotein hemagglutinin-neuraminidase (HN), which is
      responsible for cell attachment, promotion of fusion and release of progeny
      virions. This multifunctional nature of HN makes it an attractive target for the
      development of inhibitors as a treatment for childhood respiratory diseases. Here
      we report the crystal structure of NDV HN in complex with a derivative of 2-deoxy
      2,3-dehydro-N-acetylneuraminic acid, Neu5Ac2en, that has a functional group
      designed to occupy a large conserved binding pocket around the active site. The
      purpose of this study was to examine the effect of a bulky hydrophobic group at
      the O4 position of Neu5Ac2en, given the hydrophobic nature of the binding pocket.
      This derivative, with a benzyl group added to the O4 position of Neu5Ac2en, has
      an IC(50) of approximately 10 microM in a neuraminidase assay against hPIV3 HN.
      The IC(50) value of the parent compound, Neu5Ac2en, in the same assay is
      approximately 25 microM. These results highlight the striking difference between
      the influenza neuraminidase and paramyxovirus HN active sites, and provide a
      platform for the development of improved HN inhibitors.

PMID- 16575533
TI  - Addendum to "aggressive spinal germinoma with ascending metastases".

PMID- 16575532
TI  - Effects of syngeneic cellular vaccinations alone or in combination with GM-CSF on
      the weakly immunogenic F98 glioma model.
AB  - Cancer vaccines are one approach for the treatment of brain tumors. Most
      experimental studies are performed on so-called "immunogenic" brain tumor models
      such as the rat 9L glioma which does not reflect characteristics of human
      glioblastoma. In the present study, we tested syngeneic cellular vaccinations
      alone or in combination with granulocyte-macrophage colony-stimulating factor (GM
      CSF) on the weakly immunogenic F98 glioma model. Previous studies have shown the
      efficacy of this treatment on the 9L glioma model. Fisher rats received an
      intracerebral implantation of F98 cells. Three days later, two subcutaneous
      vaccinations with irradiated F98 cells were realized in presence or absence of GM
      CSF. This scheme of vaccination induced a systemic cellular and humoral immune
      response capable of in vitro cytolytic activity against F98 cells. However, no
      significant differences in survival times were noted between vaccinated and
      untreated animals. Animals vaccinated with GM-CSF or without GM-CSF had
      respectively a survival time of 26 +/- 2.1 and 25 +/- 4.4 days following tumor
      challenge versus 26.5 +/- 2.4 days for untreated rats. Fourteen days after the
      intracerebral tumor implantation, the tumors of vaccinated animals showed a
      robust infiltration by T lymphocytes, NK cells, dendritic cells, granulocytes and
      CD11b/c+ myeloid cells. This infiltration was nearly absent in untreated animals
      except for CD11b/c+ myeloid cells. This study shows that, contrary to the 9L
      glioma model, the F98 glioma model is resistant to syngeneic cellular
      vaccinations although a strong peripheral and intratumoral immune response can be
      induced. These results suggest that the F98 glioma is an attractive model to
      understand the mechanisms of glioma immunotherapy resistance.

PMID- 16575535
TI  - Two exceptional phenomena in an anaplastic oligo-astrocytoma.

PMID- 16575534
TI  - Cystemustine in recurrent high grade glioma.
AB  - In this study, we have assessed the efficacy of a nitrosourea, cystemustine, in
      treating patients with recurrent high grade glioma with overall survival analysis
      as primary end-point. Forty-eight patients with recurrent high grade glioma (24
      glioblastomas, 17 astrocytomas and 5 oligodendrogliomas) were treated every 2
      weeks with 60 mg/m2 cystemustine by a 15 min-infusion. The median number of
      treatment cycles was 4 (range 1-17). The median overall survival was 8.3 months
      (range 1-97) and the 6- and 12-month overall survival rates were 55.3% (95% CI,
      41.3-68.6%) and 29.8% (95% CI, 18.6-44.0%), respectively. The objective response
      rate was 18.8% (95% CI, 7.7-29.9%), and 54.2% of patients had stable disease (95%
      CI, 40.1-68.3%). Multivariate analysis showed that WHO performance status,
      histology and response to cystemustine were significant prognostic factors for
      survival of patients with recurrent glioma. In conclusion, cystemustine has
      encouraging activity for patients with recurrent high grade glioma.

PMID- 16575536
TI  - Tc-99m Tetrofosmin SPECT for the differentiation of a cerebellar hemorrhage
      mimicking a brain metastasis from a renal cell carcinoma.

PMID- 16575537
TI  - Somnolence syndrome after focal radiation therapy to the pineal region: case
      report and review of the literature.
AB  - Somnolence syndrome classically occurs in children after cranial irradiation for
      acute lymphocytic leukemia. Symptoms include somnolence, fever, nausea and
      vomiting, and headache. The authors report a 29 year-old female who developed
      symptoms compatible with the somnolence syndrome after completing radiation
      therapy for a benign meningioma near the pineal region. Five weeks after
      completing conformal radiation therapy (54 Gy), she developed profound fatigue,
      headaches, and 102-degree fevers. Physical examination and routine laboratory
      work were unrevealing. Imaging was not performed. Prednisone was prescribed and
      within 1 week her symptoms had largely resolved. This is the first report of the
      somnolence syndrome after focal radiation therapy. The possible etiology of the
      somnolence syndrome is discussed.

PMID- 16575538
TI  - Predicting which children are at risk for ependymoma relapse.
AB  - Ependymomas account for 6-12% of all pediatric intracranial tumors. Despite
      complete resection and radiation, about 50% of patients relapse and have
      subsequent dismal prognoses. As no clinical findings reliably forecast tumor
      recurrence, we sought to determine if gene expression profiling could be used to
      distinguish patients at high risk for relapse at initial diagnosis, and thereby
      make them candidates for innovative treatments at an early stage. We extracted
      RNA from 13 ependymoma specimens: 7 from patients who experienced tumor
      recurrence, and 6 from patients who have not recurred. RNA was applied to
      Affymetrix HG-U133 plus 2.0 microarray chips, and microarrays were analyzed with
      GeneSpring 7.0 and Prediction Analysis of Microarrays (PAM) software. The 3-gene
      subset of PLEK (pleckstrin), NF-kappaB2 (nuclear factor kappa beta-2), and
      LOC374491 (TPTE and PTEN homologous inositol phosphatase pseudogene) was
      identified as the minimal subset capable of accurately distinguishing tumors
      according to recurrence. In summary, gene expression profiling may be valuable,
      perhaps in combination with clinical findings identified in some studies, for
      identifying children at high risk for ependymoma relapse.

PMID- 16575539
TI  - Posterior third ventricular meningioma masquerading a pineal tumour.

PMID- 16575540
TI  - Treatment recommendations for the various subgroups of neurocytomas.
AB  - Neurocytomas gained importance since 1995, which is reflected by the increasing
      number of reports on this entity. This study was performed to determine the best
      available treatment for typical and atypical neurocytomas (MIB-1 labeling index
      >3%, atypical histology) in various age groups ( <or=18 years, >18 years). The
      data of all neurocytoma patients reported since 1982, when this entity were
      reviewed for age, gender, extent of resection, MIB-1 labeling index, histology,
      radiotherapy, and outcome of therapy. Patients were treated with complete
      resection alone (CTR), CTR plus radiotherapy (CTR + RT), incomplete resection
      alone (ITR), or ITR plus radiotherapy (ITR + RT). If the reported data were
      incomplete, the authors were contacted for additional data. Follow up had to be
      at least 12 months. Data were complete in 438 patients (73 children, 365 adults).
      Three hundred and fifty-one patients had typical, 87 atypical lesions. Typical
      lesions were associated with better local control and survival than atypical
      lesions (P < 0.001). CTR was superior to ITR (P < 0.001). After CTR, outcome was
      not significantly improved by RT. After ITR, RT improved survival in typical
      lesions (P = 0.03) and atypical lesions (P = 0.05), not in children (P = 0.16).
      Local control was improved in all groups (P < 0.001, children P = 0.01). Doses
      >54 Gy appeared beneficial after ITR of atypical lesions. In children, <or=50 Gy
      and >50 Gy were comparable.CTR does not require post-operative RT. Following ITR,
      RT improves outcome. Of 50-54 Gy appear sufficient for typical lesions, 50 Gy for
      children. Atypical lesions require 56-60 Gy.

PMID- 16575541
TI  - Synthetic Smac peptide enhances the effect of etoposide-induced apoptosis in
      human glioblastoma cell lines.
AB  - Smac/DIABLO is a mitochondrial protein released into cytosol during the
      progression of apoptosis. Smac/DIABLO promotes apoptosis by neutralizing the
      inhibitory effect of the inhibitor of apoptosis proteins (IAPs) on the processing
      and activity of the effecter of caspase. Here, we generated synthetic Smac
      peptide which possesses an IAP-binding domain and Drosophila antennapaedia
      penetration sequence, and examined whether it enhances the effect of the
      chemotherapeutic agent etoposide in the human glioblastoma cell line. Cellular
      uptake of Smac peptide in several glioma cell lines was most prominent at 6-12 h
      after addition. Caspase activity assay showed that our peptide successfully
      increased the activity of caspase-3 and caspase-9 in etoposide-induced apoptosis.
      In addition, Smac peptide increased the amount of cleaved PARP (poly ADP-ribose
      polymerase), but control peptides did not. Moreover, the addition of z-VAD-fmk, a
      caspase inhibitor, counterbalanced the effect of Smac peptide. Finally, we
      demonstrated that Smac peptide could enhance the growth inhibition effect of
      etoposide compared with control peptides. These results suggest that synthetic
      Smac peptide may be a new molecular targeting anti-tumor therapy for human
      glioblastoma.

PMID- 16575543
TI  - Documentary bioethics: visual narratives for Generations X and Y.
AB  - Narrative bioethics is primarily understood to involve storytelling through the
      use of literature. This article suggests that other forms of media are necessary
      to convey stories of an ethical nature to an audience broader than one being
      trained as medical professionals. "Documentary bioethics" is a manner to present
      and interpret stories of an ethical nature using forms of popular electronic
      media in a reality-based documentary style to society at large, specifically
      Generations X and Y.

PMID- 16575544
TI  - Medical humanism in the poetry of Raymond Carver.
AB  - There is an analogy between a scientific approach to medicine in which the
      patient ultimately becomes an object of study rather than a whole person, and a
      post/modern aesthetic in literature in which the subject has little or no agency
      in a chaotic linguistic universe. Raymond Carver died of cancer in 1988, and in
      both his pre- and post-diagnostic poetry there is humanistic lyricism that
      contributes to re-establishing empathic bonds between readers and characters, and
      to re-humanizing the patient as a whole person in the context of contemporary
      health institutions. Close readings of poems with descriptions of the autopsy
      room and of patient-doctor relations bring out the medical humanism in Carver's
      verse.

PMID- 16575545
TI  - The limits of narrative and culture: reflections on Lorrie Moore's "People Like
      That Are the Only People Here: Canonical Babbling in Peed Onk".
AB  - This article provides a discussion of the limits of both narrative and culture
      based on a close textual analysis of the short story, "People Like That Are the
      Only People Here: Canonical Babbling in Peed Onk," by Lorrie Moore. In this
      story, a mother describes her experiences on a pediatric oncology ward when her
      infant son develops Wilms' tumor. The authors examine how the story satirically
      portrays the spurious claims of language, story, and culture to protect us from
      an unjust universe and then exposes their false promises. The various personal,
      professional, and genre-specific narratives we use to create order and coherence
      from the terror of serious illness are ultimately ineffective. Similarly, the
      superficially comforting culture of the hospital ward cares more about creating
      the illusion of control than it does about the suffering of sick children.
      Language and culture cannot make sense of human anguish, the article concludes,
      yet they are all we have to hold back the chaos. Mystery and uncertainty, as part
      of the human condition, must become part of our stories and part of our culture.

PMID- 16575542
TI  - Executive functioning in children with an Autism Spectrum Disorder: can we
      differentiate within the spectrum?
AB  - The aim of this study was to investigate whether children with high-functioning
      autism (HFA), Asperger's syndrome (AS), and pervasive developmental disorder not
      otherwise specified (PDDNOS) can be differentiated from each other and from
      normal controls on their neurocognitive executive functioning (EF) profile.
      Children with HFA and AS showed the most EF deficits. The EF profile of the
      PDDNOS group was more disturbed that the normal control group, but was less
      disturbed than the profile of the HFA and AS groups. Little difference was found
      between the three PDD subtypes with respect to EF. This study supports the view
      that executive dysfunctioning plays an important role in autism. The usefulness
      of a distinction between different PDD subtypes was not demonstrated.

PMID- 16575547
TI  - The effects of sperm quality on embryo development after intracytoplasmic sperm
      injection.
AB  - PURPOSE: To explore the possible relationship between sperm quality and embryo
      development, pregnancy and implantation rates, in patients undergoing
      intracytoplasmic sperm injection (ICSI). METHODS: Fertilization and cleavage
      rates, quality of embryos, blastocyst development, pregnancy and implantation
      rates were analyzed in 1020 embryos from 219 couples undergoing first ICSI
      treatment cycle. The couples were allocated in five groups, according to semen
      parameters: Group 1: patients with normal semen parameters, Group 2: patients
      with mild oligo-astheno-teratozoospermia, Group 3: patients with severe oligo
      astheno-teratozoospermia, Group 4: patients with obstructive azoospermia, Group
      5: patients with non-obstructive azoospermia. RESULTS: Fertilization and cleavage
      rates, quality of embryos as well as blastocyst development rates were
      significantly reduced, as semen quality decreased. However, no significant
      differences were observed in clinical pregnancy and implantation rates.
      CONCLUSION: Overall, a negative relationship was observed between semen quality
      and embryo development, even before activation of the embryonic genome,
      suggesting that sperm can affect embryogenesis from a very early stage.

PMID- 16575548
TI  - Changes in the ratio of Bax and Bcl-2 mRNA expression and their cellular
      localization throughout the ovulatory cycle in the human oviduct.
AB  - PURPOSE: To examine changes in the ratio of Bax and Bcl-2 mRNA expression
      throughout the ovulatory cycle in the ampullary region of the human oviduct.
      METHODS: The mucosal layer was isolated from the human oviduct tissue and
      semiquantitative reverse-transcriptase polymerase chain-reaction (RT-PCR)
      analysis of mRNA of Bax and Bcl-2 was performed. Immunohistochemistry provided
      the cellular localization of the Bax and Bcl-2 proteins. The ratio of expression
      of Bax and Bcl-2 mRNA was examined in the ampullary region of the oviduct in
      samples obtained in the follicular, periovulatory, and luteal phases of the
      ovulatory cycle. RESULTS: Bax expression was constant in the follicular and
      periovulatory phase but showed a significant increase in the luteal phase. The
      Bax protein was present in all oviduct mucosal epithelial cells and the intensity
      of staining increased in luteal phase samples. Bcl-2 was expressed at a
      relatively constant level throughout the ovulatory cycle. The Bcl-2 protein was
      present in some but not all mucosal epithelial cells and the proportion of
      positive cells remained constant throughout the ovulatory cycle. CONCLUSION: The
      proapoptotic gene Bax shows a significant increase in mRNA expression in the
      luteal phase of the ovulatory cycle while the expression level of the
      antiapoptotic gene Bcl-2 remains constant throughout the ovulatory cycle. The
      ratio of Bax:Bcl-2 increases significantly in the luteal phase consistent with
      cells undergoing apoptosis.

PMID- 16575549
TI  - Fluorescence of a benzothienopyridopyrimidone in solution and in lipid vesicles.
AB  - Fluorescence properties of a biologically active benzothienopyridopyrimidone in
      solution and in lipid vesicles are reported. Assays at different pH values (0.5
      10) allowed the determination of pK(a) = 2.0, showing that this compound may be
      useful as a pH indicator for pH < or = 4. In lipid vesicles,
      benzothienopyridopyrimidone locates in a water-rich environment, indicating that
      it can be carried in the hydrophilic region of liposomes for drug delivery
      applications.

PMID- 16575550
TI  - Theory of directed electronic energy transfer.
AB  - The migration of electronic energy between molecules or chromophores in molecular
      solids is a well-studied phenomenon. The ability to exert control over the
      directionality of this transfer, by a variety of methods involving applied
      electrical or optical fields, holds promise for advances in fields including
      nanoelectronics and energy harvesting materials. In this paper, we review in
      detail a number of methods for directing energy transfer, also identifying
      potential applications.

PMID- 16575551
TI  - Early detection of plant stress from changes in distributions of chlorophyll a
      fluorescence parameters measured with fluorescence imaging.
AB  - In this work, we used barley leaves suffering from a stress, for measurements of
      chlorophyll a fluorescence with an imaging fluorometer. We compared selected
      fluorescence parameters (FP) determined from the measurements of control (no
      stress) and afterwards stressed sample by classical statistical comparison (Mann
      Whitney test) and by statistical comparison of shapes of distributions of the FPs
      (two-sample Smirnov test). We have found that there exist examples where
      statistically significant difference is not revealed using the classical
      statistical comparison (for given critical level), but statistically significant
      difference is revealed using comparisons of distributions (for the same critical
      level). It implies that the shape of statistical distribution of a FP is more
      sensitive to a stress of a sample than median of the FP. Further, the comparison
      of changes in shapes of statistical distributions of FPs is therefore more
      suitable for early detection of plant stress than a classical statistical
      comparison. The observed changes in the distributions of FPs are discussed.

PMID- 16575552
TI  - Increased frontal and paralimbic activation following ayahuasca, the pan
      Amazonian inebriant.
AB  - RATIONALE: Ayahuasca is a South American psychoactive plant tea which contains
      the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and monoamine-oxidase
      inhibitors that render DMT orally active. Previous investigations with ayahuasca
      have highlighted a psychotropic effect profile characterized by enhanced
      introspective attention, with individuals reporting altered somatic perceptions
      and intense emotional modifications, frequently accompanied by visual imagery.
      Despite recent advances in the study of ayahuasca pharmacology, the neural
      correlates of acute ayahuasca intoxication remain largely unknown. OBJECTIVES: To
      investigate the effects of ayahuasca administration on regional cerebral blood
      flow. METHODS: Fifteen male volunteers with prior experience in the use of
      psychedelics received a single oral dose of encapsulated freeze-dried ayahuasca
      equivalent to 1.0 mg DMT/kg body weight and a placebo in a randomized double
      blind clinical trial. Regional cerebral blood flow was measured 100-110 min after
      drug administration by means of single photon emission tomography (SPECT).
      RESULTS: Ayahuasca administration led to significant activation of frontal and
      paralimbic brain regions. Increased blood perfusion was observed bilaterally in
      the anterior insula, with greater intensity in the right hemisphere, and in the
      anterior cingulate/frontomedial cortex of the right hemisphere, areas previously
      implicated in somatic awareness, subjective feeling states, and emotional
      arousal. Additional increases were observed in the left amygdala/parahippocampal
      gyrus, a structure also involved in emotional arousal. CONCLUSIONS: The present
      results suggest that ayahuasca interacts with neural systems that are central to
      interoception and emotional processing and point to a modulatory role of
      serotonergic neurotransmission in these processes.

PMID- 16575553
TI  - Effects of dopamine D1 receptor agonists in rats trained to discriminate
      dihydrexidine.
AB  - RATIONALE: The full D1 receptor agonist dihydrexidine (DHX) [(+/-)-trans-10,11
      dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine hydrochloride] is under
      clinical development (DAR-100) for Parkinson's disease and schizophrenia. Despite
      the clinical development of DHX, very little is known about its discriminative
      stimulus properties in rats. To more fully characterize the discriminative
      stimulus properties of DHX, we trained rats to discriminate DHX (3 mg/kg, i.p.)
      from vehicle. METHODS: Substitution tests in rats discriminating DHX (3 mg/kg,
      i.p.) from vehicle were performed with structurally distinct D1 receptor agonists
      with both partial and full intrinsic efficacy. In addition, the peripherally
      restricted D1 agonist, fenoldopam, was evaluated. RESULTS: SKF 75670A, ABT-431,
      dinapsoline, SKF 81297, and SKF 82958 all fully substituted in a dose-dependent
      manner. The rank order of potency for substitution was SKF 82958<ABT-431<SKF
      75670A<or=dinapsoline<SKF 81297<DHX. Fenoldopam (10 and 30 mg/kg) did not
      substitute and was without effect on rates of responding. CONCLUSIONS: DHX
      produces prominent dopamine D1 receptor agonist effects in vivo and is likely to
      produce subjective effects in humans similar to other D1 receptor agonists.

PMID- 16575554
TI  - [Burns surgery].

PMID- 16575555
TI  - [Early surgical management of severe burns].
AB  - The success of modern burn therapy is based on an understanding of the
      pathophysiology and application of burn intensive care implying fluid
      resuscitation and management of pulmonary or other organ failure. With the
      development of early eschar excision and wound closure by immediate grafting,
      survival and cosmetic outcome were further improved. Especially in post-acute
      therapy, early physical rehabilitation, early reintegration, and early plastic
      surgical correction of the sequelae are indispensable for the outcome.

PMID- 16575556
TI  - Anatomical study of the confluence of the sinuses with contrast-enhanced magnetic
      resonance venography.
AB  - INTRODUCTION: It is important that each dural sinus can be recognized during
      brain surgery and that the venous route can be used for interventional
      procedures. In this study, the anatomical features and patterns of the confluence
      of the sinuses were analyzed. METHODS: The technique of contrast-enhanced three
      dimensional magnetic resonance venography was used in 549 patients. RESULTS:
      There were many anatomical variations in the confluence of the sinuses. Most
      cases had wide communication between the right and left transverse sinuses.
      CONCLUSION: Careful examination of the confluence of the sinuses is essential for
      the preoperative evaluation of posterior cranial fossa lesions and interventional
      procedures using the venous route.

PMID- 16575557
TI  - Purification and characterization of a fibrinolytic enzyme of Bacillus subtilis
      DC33, isolated from Chinese traditional Douchi.
AB  - Bacillus subtilis DC33 producing a novel fibrinolytic enzyme was isolated from Ba
      bao Douchi, a traditional soybean-fermented food in China. The strong fibrin
      specific enzyme subtilisin FS33 was purified to electrophoretic homogeneity using
      the combination of various chromatographic steps. The optimum temperature, pH
      value, and pI of subtilisin FS33 were 55 degrees C, 8.0, and 8.7, respectively.
      The molecular weight was 30 kDa measured by SDS-PAGE under both reducing and non
      reducing conditions. The enzyme showed a level of fibrinolytic activity that was
      about six times higher than that of subtilisin Carlsberg. The first 15 amino acid
      residues of N-terminal sequence of the enzyme were A-Q-S-V-P-Y-G-I-P-Q-I-K-A-P-A,
      which are different from that of other known fibrinolytic enzymes. The amidolytic
      activities of subtilisin FS33 were inhibited completely by 5 mM
      phenylmethanesulfonyl fluoride (PMSF) and 1 mM soybean trypsin inhibitor (SBTI),
      but 1,4-dithiothreitol (DTT), beta-mercaptoethanol, and p-hydroxymercuribenzoate
      (PHMB) did not affect the enzyme activity; serine and tryptophan are thus
      essential in the active site of the enzyme. The highest affinity of subtilisin
      FS33 was towards N-Succ-Ala-Ala-Pro-Phe-pNA. Therefore, the enzyme was considered
      to be a subtilisin-like serine protease. The fibrinolytic enzyme had a high
      degrading activity for the Bbeta-chains and Aalpha-chain of fibrin(ogen), and
      also acted on thrombotic and fibrinolytic factors of blood, such as plasminogen,
      urokinase, thrombin, and kallikrein. So subtilisin FS33 was able to degrade
      fibrin clots in two ways, i.e., (a) by forming active plasmin from plasminogen
      and (b) by direct fibrinolysis.

PMID- 16575558
TI  - Increased prevalence of Down's syndrome in individuals with type 1 diabetes in
      Denmark: A nationwide population-based study.
AB  - AIMS/HYPOTHESIS: In patients with Down's syndrome, dogma has long held that the
      prevalence of diabetes is increased. The aim of the present study was to
      determine the actual prevalence of Down's syndrome among type 1 diabetic
      patients. SUBJECTS, MATERIALS AND METHODS: The background population included all
      children born in Denmark between 1981 and 2000. Registry-validated and clinical
      data on type 1 diabetes and Down's syndrome diagnoses were obtained from the
      National Disease Register and Danish Cytogenetic Central Register, respectively.
      RESULTS: The prevalence of Down's syndrome in the background population was
      0.09%, whereas we identified a prevalence of Down's syndrome in type 1 diabetes
      patients of 0.38% (95% CI 0.17-0.75), corresponding to a 4.2-fold increased
      prevalence compared with the background population (p = 7.3 x 10(-5)).
      CONCLUSIONS/INTERPRETATION: To the best of our knowledge this is the first
      population-based study addressing the prevalence of Down's syndrome among
      verified type 1 diabetes patients. A more than fourfold increased prevalence of
      Down's syndrome among type 1 diabetes patients supports the notion that genes on
      chromosome 21 may confer risk for type 1 diabetes, probably also in the general
      population.

PMID- 16575559
TI  - Insights into the role of anaplerosis in insulin secretion: A 13C NMR study.
AB  - AIMS/HYPOTHESIS: Defining mechanisms and enzymatic paths critical to fuel
      regulated insulin secretion are key goals of diabetes research. In this study,
      13C-nuclear magnetic resonance spectroscopy and isotopomer analysis were used to
      investigate the link between insulin secretion and metabolic pathways associated
      with the tricarboxylic acid (TCA) cycle. MATERIALS AND METHODS: To this end, four
      insulinoma cell lines (betaTC3, betaTC-tet, INS-1 [832/13], R7T1) and porcine
      islets were examined under a variety of culture conditions (i.e. presence vs
      absence of amino acids and sera, and low vs high glucose). RESULTS: Glucose
      consumption, insulin release, and glutamate isotopomeric patterns were influenced
      by media complexity (e.g. PBS, plain culture media, fully supplemented culture
      media). The 13C-labelled metabolites increased with media complexity and
      increasing glucose concentration, with the notable exception of aspartate, which
      was always higher under low-glucose conditions. The 13C-glutamate isotopomeric
      fractions were fitted to metabolic models to estimate the relative metabolic
      fluxes to the TCA cycle through key enzymatic processes. These indices of
      metabolism were compared with insulin secretion to determine correlative links. A
      model containing a single pool of pyruvate, an entrance to the TCA cycle via the
      pyruvate dehydrogenase complex, and two anaplerotic entrances, one through
      pyruvate carboxylase and another through an undefined (by the modelling program)
      source, provided the best fit to the data under all conditions tested, for all
      cell lines. CONCLUSIONS/INTERPRETATION: On the basis of our findings, a strong
      correlation may exist between stimulated insulin secretion and non-pyruvate
      carboxylase anaplerosis for the four cell lines examined in this study.

PMID- 16575561
TI  - Oxygen limitation is a pitfall during screening for industrial strains.
AB  - Oxygen supply is a key parameter in aerobic fermentation processes like the
      industrial production of amino acids. Although the oxygen transfer rate (OTR; or
      the volumetric oxygen transfer coefficient k(L)a) is routinely analyzed by
      engineers during stirred tank fermentations, it is often not taken into account
      by biologists conducting screening experiments in shake flasks. To show the
      importance of knowing how to avoid oxygen transfer limitations during primary
      screenings, Corynebacterium glutamicum ATCC 13032 (wild-type strain) and DSM
      12866 (lysine-producing strain) were cultivated in shake flasks with different
      culture liquid volumes and under different shaking conditions. With the
      Respiration Activity Monitoring System, the OTR was determined quasi
      continuously. Optical density as well as concentrations of lysine and byproducts
      (lactate, acetate, succinate) were determined off-line and correlated with the
      OTR signal. From the results, design criteria for improved screening in shaken
      bioreactors that help to avoid selection of suboptimal strains during early
      process development steps can be derived. Finally, the suitability of DSM 12866
      as a strain for industrial processes with a high space-time yield is discussed.

PMID- 16575562
TI  - Hypoglycemic activity of the fungi Cordyceps militaris, Cordyceps sinensis,
      Tricholoma mongolicum, and Omphalia lapidescens in streptozotocin-induced
      diabetic rats.
AB  - Crude extracts were prepared from fruiting bodies and mycelia of the medicinal
      fungus Cordyceps militaris, and a polysaccharide-enriched fraction was obtained
      after extraction with hot water and ethanol precipitation. Polysaccharide
      enriched fractions were similarly prepared from Cordyceps sinensis, Omphalia
      lapidescens, and Tricholoma mongolicum. The various aforementioned preparations
      were orally administered into different groups of adult rats 24 h before an
      intraperitoneal injection of streptozotocin (40 mg/kg body weight), and
      subsequently daily for another 4 days. The dosage used was 10 mg/kg body weight
      for polysaccharide-enriched preparations and 100 mg/kg body weight for crude
      extracts. Control rats received distilled water instead of crude extract or
      polysaccharide-enriched preparation. It was found in the control rats that plasma
      glucose level rose from about 90 mg/dl before streptozotocin injection to levels
      that were maintained at about 300 mg/dl postinjection. All preparations produced
      hypoglycemic effects. C. militaris polysaccharide-enriched fraction displayed a
      more prominent effect than that of C. sinensis polysaccharide-enriched fraction
      which in turn was more potent than that of O. lapidescens and T. mongolicum
      polysaccharide-enriched fractions. The hypoglycemic effect of C. militaris
      polysaccharide-enriched fraction was dose-dependent.

PMID- 16575560
TI  - Complete chloroplast genome sequences of Solanum bulbocastanum, Solanum
      lycopersicum and comparative analyses with other Solanaceae genomes.
AB  - Despite the agricultural importance of both potato and tomato, very little is
      known about their chloroplast genomes. Analysis of the complete sequences of
      tomato, potato, tobacco, and Atropa chloroplast genomes reveals significant
      insertions and deletions within certain coding regions or regulatory sequences
      (e.g., deletion of repeated sequences within 16S rRNA, ycf2 or ribosomal binding
      sites in ycf2). RNA, photosynthesis, and atp synthase genes are the least
      divergent and the most divergent genes are clpP, cemA, ccsA, and matK. Repeat
      analyses identified 33-45 direct and inverted repeats >or=30 bp with a sequence
      identity of at least 90%; all but five of the repeats shared by all four
      Solanaceae genomes are located in the same genes or intergenic regions,
      suggesting a functional role. A comprehensive genome-wide analysis of all coding
      sequences and intergenic spacer regions was done for the first time in
      chloroplast genomes. Only four spacer regions are fully conserved (100% sequence
      identity) among all genomes; deletions or insertions within some intergenic
      spacer regions result in less than 25% sequence identity, underscoring the
      importance of choosing appropriate intergenic spacers for plastid transformation
      and providing valuable new information for phylogenetic utility of the
      chloroplast intergenic spacer regions. Comparison of coding sequences with
      expressed sequence tags showed considerable amount of variation, resulting in
      amino acid changes; none of the C-to-U conversions observed in potato and tomato
      were conserved in tobacco and Atropa. It is possible that there has been a loss
      of conserved editing sites in potato and tomato.

PMID- 16575563
TI  - Revealing the complementation of ferredoxin by cytochrome b (5) in the Spirulina-
      (6)-desaturation reaction by N-terminal fusion and co-expression of the fungal
      cytochrome b (5) domain and Spirulina- (6)-acyl-lipid desaturase.
AB  - Spirulina-acyl-lipid desaturases are integral membrane proteins found in
      thylakoid and plasma membranes. These enzymes catalyze the fatty acid
      desaturation process of Spirulina to yield gamma-linolenic acid (GLA) as the
      final desaturation product. It has been reported that the cyanobacterial
      desaturases use ferredoxin as an electron donor, whereas the acyl-lipid
      desaturase in plant cytoplasm and the acyl-CoA desaturase of animals and fungi
      use cytochrome b (5). The low level of ferredoxin present in Escherichia coli
      cells leads to an inability to synthesize GLA when the cells are transformed with
      the Spirulina-(6) desaturase, desD, and grown in the presence of the reaction
      substrate, linoleic acid. In this study, Spirulina-(6) desaturase, encoded by the
      desD gene, was N-terminally fused and co-expressed with the cytochrome b (5)
      domain from Mucor rouxii. The product, GLA, made heterologously in E. coli and
      Saccharomyces cerevisiae, was then detected and analyzed. The results revealed
      the production of GLA by Spirulina-(6) desaturase fused or co-expressed with
      cytochrome b (5) in E. coli cells, in which GLA production by this gene cannot
      occur in the absence of cytochrome b (5). Moreover, the GLA production ability in
      the E. coli host cells was lost after the single substitution mutation was
      introduced to H52 in the HPGG motif of the cytochrome b (5) domain. These results
      revealed the complementation of the ferredoxin requirement by the fusion or co
      expression of the fungal-cytochrome b (5) domain in the desaturation process of
      Spirulina-(6) desaturase. Furthermore, the free form of cytochrome b (5) domain
      can also enhance GLA production by the Spirulina-desD gene in yeast cells.

PMID- 16575564
TI  - Ethanol fermentation from lignocellulosic hydrolysate by a recombinant xylose-
      and cellooligosaccharide-assimilating yeast strain.
AB  - The sulfuric acid hydrolysate of lignocellulosic biomass, such as wood chips,
      from the forest industry is an important material for fuel bioethanol production.
      In this study, we constructed a recombinant yeast strain that can ferment xylose
      and cellooligosaccharides by integrating genes for the intercellular expressions
      of xylose reductase and xylitol dehydrogenase from Pichia stipitis, and
      xylulokinase from Saccharomyces cerevisiae and a gene for displaying beta
      glucosidase from Aspergillus acleatus on the cell surface. In the fermentation of
      the sulfuric acid hydrolysate of wood chips, xylose and cellooligosaccharides
      were completely fermented after 36 h by the recombinant strain, and then about 30
      g/l ethanol was produced from 73 g/l total sugar added at the beginning. In this
      case, the ethanol yield of this recombinant yeast was much higher than that of
      the control yeast. These results demonstrate that the fermentation of the
      lignocellulose hydrolysate is performed efficiently by the recombinant
      Saccharomyces strain with abilities for xylose assimilation and
      cellooligosaccharide degradation.

PMID- 16575565
TI  - High yield expression of lipase A from Candida antarctica in the methylotrophic
      yeast Pichia pastoris and its purification and characterisation.
AB  - The current investigation focuses on shedding further light on the
      characteristics of lipase A from Candida antarctica (CalA), which has attracted
      growing attention in its suitability for industrial applications. CalA was
      functionally expressed in the methylotrophic yeast Pichia pastoris, purified and
      characterised. A classical fed-batch process and a semi-continuous process were
      developed and tested with regard to their yield capacity. Lipase concentrations
      of 0.88 and 0.55 g l(-1) were obtained using the fed-batch and semi-continuous
      processes, respectively. The semi-continuous process reaches a total activity of
      10,233,000 U and so surpasses the fed-batch process reaching 7,530,000 U. The
      purified enzyme showed highest activity between 50 and 70 degrees C at pH 7.0 and
      a preference for short-chain triglycerides (C4-C8). Significantly reduced
      activity was observed in the presence of hydrophilic esters.

PMID- 16575566
TI  - Development of a defined medium supporting rapid growth for Deinococcus
      radiodurans and analysis of metabolic capacities.
AB  - A morpholinepropanesulfonic acid (MOPS)-buffered rich defined medium (RDM) was
      optimized to support a reproducible 2.6-h doubling time at 35 degrees C for
      Deinococcus radiodurans R1 and used to gain insight into vitamin and carbon
      metabolism. D. radiodurans was shown to require biotin and niacin for growth in
      this medium. A glutamine-serine simple defined medium (SDM) was developed that
      supported a 4-h doubling time, and this medium was used to probe sulfur and
      methionine metabolism. Vitamin B(12) was shown to alleviate methionine
      auxotrophy, and under these conditions, sulfate was used as the sole sulfur
      source. Phenotypic characterization of a methionine synthase deletion mutant
      demonstrated that the B(12) alleviation of methionine auxotrophy was due to the
      necessity of the B(12)-dependent methionine synthase in methionine biosynthesis.
      Growth on ammonium as the sole nitrogen source in the presence of vitamin B(12)
      was demonstrated, but it was not possible to achieve reproducibly good growth in
      the absence of at least one amino acid as a nitrogen source. Growth on sulfate,
      cysteine, and methionine as sulfur sources demonstrated the function of a
      complete sulfur recycling pathway in this strain. These studies have demonstrated
      that rapid growth of D. radiodurans R1 can be achieved in a MOPS-based medium
      solely containing a carbon source, salts, four vitamins, and two amino acids.

PMID- 16575567
TI  - Production of lipopeptide antibiotic iturin A using soybean curd residue
      cultivated with Bacillus subtilis in solid-state fermentation.
AB  - Bacillus subtilis RB14-CS, which suppresses the growth of various plant pathogens
      in vitro by producing the lipopeptide antibiotic iturin A, was cultured using
      soybean curd residue, okara, a by-product of tofu manufacture in solid-state
      fermentation. After 4 days incubation, iturin A production reached 3,300 mg/kg
      wet solid material (14 g/kg dry solid material), which is approximately tenfold
      higher than that in submerged fermentation. When the okara product cultured with
      RB14-CS was introduced into soil infested with Rhizoctonia solani, which is a
      causal agent of damping-off of tomato, the disease occurrence was significantly
      suppressed. After 14 days, the number of RB14-CS cells remained in soil at the
      initial level, whereas almost no iturin A was detected in soil. As the okara
      cultured with RB14-CS exhibited functions of both plant disease suppression and
      nutritional effect on tomato seedlings, this product is expected to contribute to
      the recycling of the soybean curd residue.

PMID- 16575568
TI  - Functional solubilization of aggregation-prone TRAIL protein facilitated by
      coexpressing with protein isoaspartate methyltranferase.
AB  - TRAIL was a tumor-specific protein in development as a novel anticancer
      therapeutic agent. Generally, when expressed in recombinant Escherichia coli,
      TRAIL protein was prone to form inclusion bodies. In this study, coexpression of
      human TRAIL protein and protein isoaspartate methyltranferase (PIMT) from E. coli
      on plasmid pBV-TRAIL-PCM in E. coli C600 was investigated to overcome the
      difficulties in soluble expression. The results showed that this PIMT
      coexpression strategy exerted a positive effect on the TRAIL protein expression
      in recombinant E. coli, which led to a mean increase in the intracellular
      concentration of soluble and total protein of TRAIL by 1.57-fold and 1.33-fold,
      respectively. At the same time, results also suggested that PIMT was a
      prospective partner for soluble expression of TRAIL protein.

PMID- 16575569
TI  - H2S degradation is reflected by both the activity and composition of the
      microbial community in a compost biofilter.
AB  - In this study, 16S rRNA- and rDNA-based denaturing gradient gel electrophoresis
      (DGGE) were used to study the temporal and spatial evolution of the microbial
      communities in a compost biofilter removing H(2)S and in a control biofilter
      without H(2)S loading. During the first 81 days of the experiment, the H(2)S
      removal efficiencies always exceeded 93% at loading rates between 4.1 and 30 g m(
      3) h(-1). Afterwards, the H(2)S removal efficiency decreased to values between 44
      and 71%. RNA-based DGGE analysis showed that H(2)S loading to the biofilter
      increased the stability of the active microbial community but decreased the
      activity-based diversity and evenness. The most intense band in both the RNA- and
      DNA-based DGGE patterns of the H(2)S-degrading biofilter represented the sulfur
      oxidizing bacterium Thiobacillus thioparus. This suggested that T. thioparus
      constituted a major part of the bacterial community and was an important primary
      degrader in the H(2)S-degrading biofilter. The decreasing H(2)S removal
      efficiencies near the end of the experiment were not accompanied by a substantial
      change of the DGGE patterns. Therefore, the decreased H(2)S removal was probably
      not caused by a failing microbiology but rather by a decrease of the mass
      transfer of substrates after agglutination of the compost particles.

PMID- 16575570
TI  - Growth of Escherichia coli MG1655 on LB medium: monitoring utilization of amino
      acids, peptides, and nucleotides with transcriptional microarrays.
AB  - Analysis of gene expression data related to assimilation and biosynthesis of
      nitrogen-containing compounds amino acids, peptides, and nucleotides was used to
      monitor availability of these nutrients to Escherichia coli MG1655 growing on
      Luria-Bertani medium. The data indicate that free amino acids and nucleotides
      only transiently support the nitrogen requirement for growth and are no longer
      available by 3.5 h of fermentation. The resulting shortage of available nitrogen
      sources induces the Ntr response, which involves induction of the glnALG, glnK
      amtB, dppABCDF, and oppABCDF operons as well as the genes coding for outer
      membrane proteins, porins OmpA and OmpC, and proteases OmpP and OmpT. The
      increased uptake of peptides facilitated by the products of dppABCDF, oppABCDF,
      ompA, ompC, ompP, and ompT alleviates nitrogen limitation of the growth.

PMID- 16575572
TI  - Genomic instability in phenotypically normal regenerants of medicinal plant
      Codonopsis lanceolata Benth. et Hook. f., as revealed by ISSR and RAPD markers.
AB  - Codonopsis lanceolata Benth. et Hook. f., commonly known as bonnet bellflower, is
      a high-valued herb medicine and vegetable. In this study, a large number of
      plants were regenerated via organogenesis from immature seed-derived calli in C.
      lanceolata by a simple and efficient method. Compared with the mother donor
      plant, the regenerated plants did not exhibit visible phenotypic variations in
      six major morphological traits examined at the stage of one-season-maturity under
      field conditions. To gain insight into the genomic stability of these regenerated
      plants, 63 individuals were randomly tagged among a population of more than 2,000
      regenerants, and were compared with the single mother donor plant by two
      molecular markers, the inter-simple sequence repeats (ISSR) and randomly
      amplified polymorphic DNA (RAPD). Apparent genomic variation was detected in the
      63 regenerants, whereas preexisting heterozygosiy in the donor plant was deemed
      minimal by testing 30 seedlings germinated from selfed seeds of the same donor
      plant. The percentages of polymorphic bands (PPB) in the ISSR and RAPD analysis
      were respectively 15.7 and 24.9% for the 63 regenerated plants. Cluster analysis
      indicates that the genetic similarity values calculated on the basis of RAPD and
      ISSR data among the 64 plants (63 regenerated and one donor) were respectively
      0.894 and 0.933, which allow classification of the plants into distinct groups.
      Nineteen randomly isolated bands underlying the changed RAPD or ISSR patterns
      were sequenced, and three of them showed significant homology to known-function
      genes. Detailed pairwise sequence comparison at one locus between the donor plant
      and a regenerant revealed that insertion of two short (24 and 19 bp) stretches of
      nucleotides in the regenerated plant relative to the donor plant occurred in an
      apparently stochastic manner.

PMID- 16575571
TI  - Prognostic factors affecting the outcome of brain metastases from breast cancer.
AB  - GOALS OF WORK: The purpose of this study is to analyze the overall survival rate
      of patients with brain metastases from breast cancer and to determine prognostic
      factors affecting outcomes of these patients. PATIENTS AND METHODS: From July
      1988 to December 2004, 48 female patients with brain metastases from breast
      cancer underwent full-dose whole-brain radiotherapy (WBRT). In these patients we
      evaluated the significance of the following factors in predicting the survival
      rate after WBRT: age, extracranial metastases, number of brain metastases, total
      dose of WBRT, Karnofsky performance status (KPS), and Radiation Therapy Oncology
      Group recursive partitioning analysis (RPA) class. RESULTS: The median overall
      survival rate was 7.3 months. The 1- and 2-year overall survival rates were 37
      and 20%, respectively. In univariate analysis, KPS (p<0.0001), number of lesions
      of brain metastases (p=0.0149), age (p=0.0452), and RPA class (p<0.0001) were
      statistically significant prognostic factors for overall survival. In
      multivariate analysis, KPS (p<0.001) and number of brain metastases (p=0.039)
      were significant prognostic factors for overall survival. CONCLUSIONS: Survival
      of breast cancer patients with brain metastases treated with WBRT is poor. To
      improve survival, enrollment of more patients with brain metastases from breast
      cancer for prospective trials involving a multimodality approach that combines
      radiation and systemic therapies based on appropriate patient triage is
      warranted.

PMID- 16575573
TI  - Fractional calculus in biomechanics: a 3D viscoelastic model using regularized
      fractional derivative kernels with application to the human calcaneal fat pad.
AB  - A viscoelastic model of the K-BKZ (Kaye, Technical Report 134, College of
      Aeronautics, Cranfield 1962; Bernstein et al., Trans Soc Rheol 7: 391-410, 1963)
      type is developed for isotropic biological tissues and applied to the fat pad of
      the human heel. To facilitate this pursuit, a class of elastic solids is
      introduced through a novel strain-energy function whose elements possess strong
      ellipticity, and therefore lead to stable material models. This elastic potential
      - via the K-BKZ hypothesis - also produces the tensorial structure of the
      viscoelastic model. Candidate sets of functions are proposed for the elastic and
      viscoelastic material functions present in the model, including two functions
      whose origins lie in the fractional calculus. The Akaike information criterion is
      used to perform multi-model inference, enabling an objective selection to be made
      as to the best material function from within a candidate set.

PMID- 16575575
TI  - Molecular modeling of the effects of mutant alleles on chalcone synthase protein
      structure.
AB  - Chalcone synthase (CHS) catalyzes the first committed step in flavonoid
      biosynthesis, a major pathway of plant secondary metabolism. An allelic series
      for the Arabidopsis CHS locus, tt4, was previously characterized at the gene,
      protein, and end-product levels. In an effort to deduce the molecular basis for
      the observed phenotypes, homology models were generated for five of the tt4
      proteins based on the crystal structure of CHS2 from Medicago. Molecular dynamics
      simulations provided insights into how even those substitutions that are not in
      close spatial proximity to key functional residues may still alter the
      architecture and dynamic movement of the enzyme, with dramatic effects on enzyme
      function. Simulations carried out at different temperatures pointed to optimized
      positioning of key residues in the active site or dimerization domain, rather
      than enhancement of overall structure, as underlying the higher activity of two
      temperature-sensitive variants at lower temperatures. Extending this type of
      analysis to account for protein-protein interactions may offer additional
      insights into the mechanisms by which single amino-acid substitutions can affect
      diverse aspects of protein function.

PMID- 16575574
TI  - A case-control study investigating the role of sulfotransferase 1A1 polymorphism
      in head and neck cancer.
AB  - PURPOSE: Sulfotransferases (SULT) 1A1 detoxify and bio-activate a broad spectrum
      of substrates including xenobiotics. The SULT1A1 gene possesses a G-->A
      polymorphism that results in an Arg to His substitution at codon 213, with the
      His allele having a low activity. The purpose of this study was to evaluate
      whether SULT1A1 Arg213His polymorphisms are risk factors for head and neck
      squamous cell carcinoma (SCCHN). METHODS: A total of 124 consecutive primary
      SCCHN patients and 249 age- and sex-matched hospital controls were enrolled in
      this study. Genomic DNA was isolated from peripheral blood lymphocytes and
      genotyping was performed by PCR-RFLP. A comprehensive epidemiological interview
      was conducted on all participants to collect their lifestyle data. RESULTS: The
      His/His frequencies in cases and controls were 6.5% (8/123) and 3.6% (9/247),
      respectively (P=0.049). Multivariate logistic regression analysis showed a
      significant association of SCCHN and His/His genotype (OR=3.60; 95% CI=1.01
      12.88). This association was stronger amongst older people, alcohol and low fruit
      consumers. The resulted SULT1A1 His/His genotype also associated with a higher
      risk of neck node positive status (OR=5.82; 95% CI=1.10-30.68). CONCLUSIONS:
      These preliminary findings show for the first time that the SULT1A1 His (213)
      allele is a possible risk factor for head and neck cancer development.

PMID- 16575577
TI  - Optimizing rapid aiming behaviour: Movement kinematics depend on the cost of
      corrective modifications.
AB  - Recent studies have shown that the initial impulse associated with goal-directed
      aiming movements typically brings the limb to a position short of the target.
      This is because target overshooting is associated with greater temporal and
      energy costs than target undershooting. Presumably these costs can be expected to
      vary not only with the muscular forces required to move the limb, but also the
      gravitational forces inherent in the aiming task. In this study we examined the
      degree to which primary movement endpoint distributions depend on the direction
      of the movement with respect to gravity. We hypothesized that the magnitude of an
      undershoot bias would be greatest for downward movements because target
      overshooting necessitates a time and energy consuming movement reversal against
      gravity. Participants completed rapid aiming movements toward targets located
      above and below, as well as proximal and distal to a central home position.
      Movements were made both with and without additional mass attached to the limb.
      Although movement time did not vary with experimental condition, primary movement
      endpoint distributions were consistent with our predictions. Specifically, both
      greater undershooting and greater endpoint variability was associated with
      downward aiming movements. As well, a greater proportion of the overall movement
      time was spent in the corrective phase of the movement. These results are
      consistent with models of energy minimization that posit an inherent efficiency
      of control and hold that movements are organized to minimize movement time and
      energy expenditure and maximize mechanical advantages.

PMID- 16575576
TI  - Generalized cortex activation by the auditory midbrain: Mediation by
      acetylcholine and subcortical relays.
AB  - The inferior colliculus (IC) is a critical component of the ascending projection
      system carrying auditory information from the brainstem to the forebrain. Recent
      evidence indicates that, in addition to its role in auditory processing, the IC
      can exert a generalized, modulatory effect on the forebrain by activating the
      neocortical electrocorticogram (ECoG). Given the sparse direct projections from
      the IC to the cortex, it appears that the effect of the IC to produce ECoG
      activation is indirect, mediated by one or several neuromodulatory systems that
      have diffuse access to the entire cortical mantle. However, the anatomical relays
      that permit the IC to influence cortical activity have not been elucidated. In
      the present experiments, electrical stimulation of the IC suppressed slow, large
      amplitude oscillations in the ECoG of urethane anesthetized rats, replacing them
      with higher-frequency cortical activation. This effect was blocked by the
      muscarinic receptor antagonist scopolamine (0.5-1.0 mg/kg, i.p.), suggestive of a
      critical role of acetylcholine (ACh) release. Consistent with this hypothesis,
      localized lidocaine infusions (2%, 1 microl) into the cholinergic basal forebrain
      complex strongly reduced ECoG activation elicited by IC stimulation. To identify
      additional relays between the IC and basal forebrain, the effects of lidocaine
      infusions into the superior colliculus, medial prefrontal cortex, midline
      thalamus, and dorsal raphe were also studied. Inactivation of the superior
      colliculus and dorsal raphe reduced IC-induced activation, while prefrontal
      cortex and thalamic infusions were ineffective. Concurrent basal forebrain and
      raphe inactivation produced effects similar to that of inactivation of the basal
      forebrain alone, suggesting that these two areas are arranged in series, rather
      than acting as independent, parallel pathways. These results suggest that the
      ability of the IC to induce ECoG activation is mediated, in large parts, by the
      basal forebrain cholinergic system. Consistent with anatomical evidence, the
      superior colliculus and dorsal raphe appear to provide important links to
      functionally connect the IC to the basal forebrain, allowing the IC to indirectly
      access the entire cortical mantle and enhance processing in neocortical networks.

PMID- 16575579
TI  - Are age-related increases in force variability due to decrements in strength?
AB  - The purpose of this investigation was to examine the relationship between
      strength and the magnitude and time sequential structure of force variability.
      Young and old adults produced isometric force via index finger abduction to a
      visually presented target corresponding to a constant force level of 5 or 25%
      maximal voluntary contraction (MVC). Cluster analysis was used to divide subjects
      into groups based on age and strength. The variability of older adults was
      greater and showed more time dependent structure than their younger counterparts.
      The force output of weaker subjects was also more variable and had a stronger
      sequential structure. Indeed, when MVC was controlled for there was no
      significant age effect on force variability. The relationship between strength
      and variability remained significant, however, when chronological age was
      controlled for. The findings revealed that the established age-related changes in
      force variability are more fundamentally due to the association between strength
      and force variability and provide a further challenge to using chronological age
      as a marker of the biological aging process in studies of motor control.

PMID- 16575578
TI  - Inhibitory and excitatory response areas of neurons in the central nucleus of the
      inferior colliculus in unanesthetized chinchillas.
AB  - In unanesthetized chinchillas, we determined excitatory and inhibitory response
      regions of neurons in the central nucleus of the inferior colliculus (ICc). The
      responses of 250 multiunits and 47 single units in the ICc to one- and two-tone
      stimuli were measured by extracellular recordings. The one-tone excitatory
      response area of ICc neurons from awake chinchillas was classified as either
      narrow with a steep high-frequency slope >140 dB/oct (type 1), broad with a high
      frequency slope <140 dB/oct (type 2), or complex with a negative high-frequency
      slope (type 3). One-tone inhibition was prominent only in units with a high
      spontaneous firing rate. As revealed with two-tone stimuli, inhibition in the ICc
      of awake chinchillas and its relation to excitatory response regions was
      different from what is reported in anesthetized animals. The two-tone inhibitory
      responses were classified as follows: (1) inhibitory regions of equal strength on
      both sides of the characteristic frequency; (2) asymmetrical inhibitory regions,
      more prominent at the high-frequency side of the characteristic frequency; (3)
      strong inhibitory regions overlying most of the one-tone excitatory response
      region; (4) inhibitory response regions lying only within the one-tone excitatory
      response region; and (5) neurons without clear two-tone inhibition. One-tone and
      two-tone inhibitory regions of the same unit were markedly different in 66% of
      the units with a high spontaneous rate. The neural response to frequencies within
      the inhibitory regions often was an onset response followed by inhibition.
      Excitatory and inhibitory response properties were similar over considerable
      penetration distances (600-1,000 microm) in a particular dorso-ventral recording
      track.

PMID- 16575580
TI  - Standard induction chemotherapy followed by attenuated consolidation in elderly
      patients with acute myeloid leukemia.
AB  - The benefits of intensive post-remission chemotherapy have not been verified in
      elderly patients with acute myeloid leukemia (AML). To reduce fatal complications
      caused by intensive post-remission therapy, we performed a prospective phase II
      multicenter trial of standard induction chemotherapy ('7+3' of cytarabine plus
      daunorubicin), followed by two cycles of attenuated consolidation therapy ('5+1'
      of cytarabine plus daunorubicin) for elderly patients with AML, excluding those
      with M3. Of the 41 patients enrolled in the study, 24 (58.5%) attained CR. Of
      these 24, 17 (70.8%) completed both planned cycles of consolidation therapy.
      After a median follow-up of 566 days (range, 63-1190 days) among surviving
      patients, 15 relapsed, with an actuarial 3-year disease-free survival rate of
      22.5%. There were no fatal complications during consolidation therapy. Actuarial
      3-year overall survival was 17.0%. These findings suggest that, when compared
      with previous findings using more intensive consolidation therapy, attenuated
      consolidation therapy does not compromise outcomes in elderly AML patients.

PMID- 16575581
TI  - Aberrations of chick eyes during normal growth and lens induction of myopia.
AB  - Understanding the control of eye growth may lead to the prevention of
      nearsightedness (myopia). Chicks develop refractive errors in response to
      defocusing lenses by changing the rate of eye elongation. Changes in optical
      image quality and the optical signal in lens compensation are not understood.
      Monochromatic ocular aberrations were measured in 16 chicks that unilaterally
      developed myopia in response to unilateral goggles with -15D lenses and in 6
      chicks developing naturally. There is no significant difference in higher-order
      root mean square aberrations (RMSA) between control eyes of the goggled birds and
      eyes of naturally developing chicks. Higher-order RMSA for a constant pupil size
      exponentially decreases in the chick eye with age more slowly than defocus. In
      the presence of a defocusing lens, the exponential decrease begins after day 2.
      In goggled eyes, asymmetric aberrations initially increase significantly,
      followed by an exponential decrease. Higher-order RMSA is significantly higher in
      goggled eyes than in controls. Equivalent blur, a new measure of image quality
      that accounts for increasing pupil size with age, exponentially decreases with
      age. In goggled eyes, this decrease also occurs after day 2. The fine optical
      structure, reflected in higher-order aberrations, may be important in
      understanding normal development and the development of myopia.

PMID- 16575582
TI  - A time series analysis of the relationship of ambient temperature and common
      bacterial enteric infections in two Canadian provinces.
AB  - The incidence of enteric infections in the Canadian population varies seasonally,
      and may be expected to be change in response to global climate changes. To better
      understand any potential impact of warmer temperature on enteric infections in
      Canada, we investigated the relationship between ambient temperature and weekly
      reports of confirmed cases of three pathogens in Canada: Salmonella, pathogenic
      Escherichia coli and Campylobacter, between 1992 and 2000 in two Canadian
      provinces. We used generalized linear models (GLMs) and generalized additive
      models (GAMs) to estimate the effect of seasonal adjustments on the estimated
      models. We found a strong non-linear association between ambient temperature and
      the occurrence of all three enteric pathogens in Alberta, Canada, and of
      Campylobacter in Newfoundland-Labrador. Threshold models were used to quantify
      the relationship of disease and temperature with thresholds chosen from 0 to -10
      degrees C depending on the pathogen modeled. For Alberta, the log relative risk
      of Salmonella weekly case counts increased by 1.2%, Campylobacter weekly case
      counts increased by 2.2%, and E. coli weekly case counts increased by 6.0% for
      every degree increase in weekly mean temperature. For Newfoundland-Labrador the
      log relative risk increased by 4.5% for Campylobacter for every degree increase
      in weekly mean temperature.

PMID- 16575583
TI  - An objective classification system of air mass types for Szeged, Hungary, with
      special attention to plant pollen levels.
AB  - This paper discusses the characteristic air mass types over the Carpathian Basin
      in relation to plant pollen levels over annual pollination periods. Based on the
      European Centre for Medium-Range Weather Forecasts dataset, daily sea-level
      pressure fields analysed at 00 UTC were prepared for each air mass type (cluster)
      in order to relate sea-level pressure patterns to pollen levels in Szeged,
      Hungary. The database comprises daily values of 12 meteorological parameters and
      daily pollen concentrations of 24 species for their pollination periods from 1997
      to 2001. Characteristic air mass types were objectively defined via factor
      analysis and cluster analysis. According to the results, nine air mass types
      (clusters) were detected for pollination periods of the year corresponding to
      pollen levels that appear with higher concentration when irradiance is moderate
      while wind speed is moderate or high. This is the case when an anticyclone
      prevails in the region west of the Carpathian Basin and when Hungary is under the
      influence of zonal currents (wind speed is high). The sea level pressure systems
      associated with low pollen concentrations are mostly similar to those connected
      to higher pollen concentrations, and arise when wind speed is low or moderate.
      Low pollen levels occur when an anticyclone prevails in the region west of the
      Carpathian Basin, as well as when an anticyclone covers the region with Hungary
      at its centre. Hence, anticyclonic or anticyclonic ridge weather situations seem
      to be relevant in classifying pollen levels.

PMID- 16575585
TI  - Genomic screening of head and neck cancer and its implications for therapy
      planning.

PMID- 16575584
TI  - Genomic screening of head and neck cancer and its implications for therapy
      planning.
AB  - Despite great technical improvements in radiotherapy and surgery, survival for
      patients with squamous cell carcinoma of the head and neck (SCCHN) has still not
      improved significantly over the last decades. Management of SCCHN has mainly been
      based on the TNM staging and site over this time period, even though we know that
      there are individual differences independent of the TNM status. Individual
      patients with small tumors might have a poor outcome, and patients with large
      tumors may end up with a favorable prognosis, despite their respective TNM
      classification. Recent molecular studies indicate that underlying genetic
      abnormalities may reflect such individual differences independently of TNM
      status. Individualization of treatment based on such biological properties of the
      tumors might result in less over as well as under treatment. However, the optimal
      panel of biomarkers to be used for the individualization of treatment is yet to
      be defined. A variety of laboratory techniques have been used in studies that
      investigate the individual biological features, spanning from methods that screen
      the genome for chromosomal and genetic abnormalities, e.g., cytogenetics, CGH,
      SKY and cDNA micro array, to detailed studies of specific aberrations. The
      purpose of this review of the literature is to summarize what has been studied so
      far by methods for genetic screening and to relate these results to the
      prediction of the clinical outcome. We conclude that it is time to focus future
      prospective studies on how treatment can be individualized based on biomarkers in
      combination with the macroscopic features of SCCHN.

PMID- 16575586
TI  - Nitric oxide biosynthesis by Leishmania amazonensis promastigotes containing a
      high percentage of metacyclic forms.
AB  - Due to the diversity of its physiological and pathophysiological functions and
      general ubiquity, the study of nitric oxide (NO) has become of great interest. In
      this work, it was demonstrated that Leishmania amazonensis promastigotes produces
      NO, a free radical synthesized from L: -arginine by nitric oxide synthase (NOS).
      A soluble NOS was purified from L. amazonensis promastigotes by affinity
      chromatography (2', 5'-ADP-agarose) and on SDS-PAGE the enzyme migrates as a
      single protein band of 116.2 (+/-6) kDa. Furthermore, the presence of a
      constitutive NOS was detected through indirect immunofluorescence using anti-cNOS
      and in NADPH consumption assays. The present work show that NO production,
      detected as nitrite in culture supernatant, is prominent in promastigotes
      preparations with high number of metacyclic forms, suggesting an association with
      the differentiation and the infectivity of the parasite.

PMID- 16575587
TI  - Weber's Law influences numerical representations in rhesus macaques (Macaca
      mulatta).
AB  - We present the results of two experiments that probe the ability of rhesus
      macaques to match visual arrays based on number. Three monkeys were first trained
      on a delayed match-to-sample paradigm (DMTS) to match stimuli on the basis of
      number and ignore continuous dimensions such as element size, cumulative surface
      area, and density. Monkeys were then tested in a numerical bisection experiment
      that required them to indicate whether a sample numerosity was closer to a small
      or large anchor value. Results indicated that, for two sets of anchor values with
      the same ratio, the probability of choosing the larger anchor value
      systematically increased with the sample number and the psychometric functions
      superimposed. A second experiment employed a numerical DMTS task in which the
      choice values contained an exact numerical match to the sample and a distracter
      that varied in number. Both accuracy and reaction time were modulated by the
      ratio between the correct numerical match and the distracter, as predicted by
      Weber's Law.

PMID- 16575588
TI  - beta 2-Adrenergic stimulation is involved in the contractile dysfunction of the
      stunned heart.
AB  - Endogenous catecholamines released during myocardial ischemia have been
      considered both to aggravate cell injury and exacerbate arrhythmias and to exert
      a protective action on the post-ischemic contractile function. The present work
      was addressed to look for evidence to explain this controversy. The effects of
      cardiac catecholamine depletion and of alpha- and beta-adrenoceptor (AR) blockade
      on the post-ischemic contractile dysfunction, as well as its possible
      relationship with cardiac oxidative stress, were studied in isolated and perfused
      rat hearts submitted to 20 min of ischemia and 30 min of reperfusion (stunning).
      Catecholamine depletion improves the contractile recovery in the stunned heart.
      This mechanical effect was associated with decreased levels of lipid
      peroxidation. A similar enhancement of the contractile function during
      reperfusion was detected after the simultaneous blockade of alpha 1- and beta-ARs
      with prazosin plus propranolol. To ascertain which specific AR pathway was
      involved in the effects of catecholamines on the stunned heart, selective AR
      blockers, prazosin (alpha 1-blocker), atenolol (beta 1-blocker), ICI 118,551
      (beta 2-blocker) and selective inhibitors of Gi-PI3K pathway (pertussis toxin and
      wortmannin) were alternatively combined. The results indicate that catecholamines
      released during ischemia exert a dual action on the contractile behavior of the
      stunned heart: a deleterious effect, related to the activation of the beta 2-AR
      Gi-PI3K-pathway, which was counteracted by a beneficial effect, triggered by the
      stimulation of alpha 1-AR. Neither the depression nor the enhancement of the post
      ischemic contractile recovery were related with the increase in ROS formation
      induced by endogenous catecholamines.

PMID- 16575590
TI  - Acute acalculous cholecystitis in a child with systemic lupus erythematosus.
AB  - A 10-year-old boy with systemic lupus erythematosus (SLE) developed abrupt right
      upper quadrant pain and vomiting during the course of his active disease.
      Antiphospholipid antibody was negative and the C3 level was low. Abdominal
      sonography showed cholecystitis with sludge balls in the gallbladder. He was
      treated by high-dose prednisolone with ceftriaxone and metronidazole IV for 3
      days but due to poor response, cholecystectomy was performed and no stone was
      identified. Histopathologic examination showed vasculitis in the medium-sized
      arteries of the gallbladder wall. He was doing well at the 9-month follow-up
      after the operation. This report describes the first pediatric case of SLE with
      acalculous cholecystitis caused by vasculitis of the gallbladder.

PMID- 16575589
TI  - Tissue factor pathway inhibitor in childhood nephrotic syndrome.
AB  - It is now recognised that the extrinsic tissue factor pathway is the main trigger
      to the coagulation system in vivo. Its main inhibitor, tissue factor pathway
      inhibitor (TFPI), has never been studied in childhood nephrotic syndrome. The aim
      of the study was to monitor the level of TFPI in childhood nephrotic syndrome.
      One hundred and thirty-nine nephrotic children were classified into the following
      groups: group 1 (n=25), in relapse and receiving no treatment; group 2 (n=37), in
      relapse but receiving steroid treatment; group 3 (n= 45), in early remission and
      on steroids; group 4 (n=24), in established remission and receiving no steroids;
      group 5 (n=8), steroid-resistant. The controls (n=84) were healthy and age
      matched. There was significant elevation of total TFPI levels in groups 1 and 2
      and 3; levels were comparable to those of the healthy controls in group 4. The
      highest levels of total TFPI were recorded in group 5. Like total TFPI, the
      levels of the free form of TFPI showed a statistically significant increase in
      groups 1, 2, 3 and 4, when compared with levels in healthy controls. The highest
      levels of free TFPI were recorded group 5. We concluded that the elevated levels
      of both the total and free TFPI in various phases of nephrotic syndrome add
      another natural anticoagulant mechanism, which will attenuate the
      hypercoagulability of childhood nephrotic syndrome.

PMID- 16575591
TI  - A novel ABA-hypersensitive mutant in Arabidopsis defines a genetic locus that
      confers tolerance to xerothermic stress.
AB  - Hot and dry air (harmattan or xerothermic climate) greatly inhibits plant growth,
      particularly flowering and seed setting of crops. Little is known about the
      mechanism of plant response to this extreme environmental stress due to the lack
      of valuable genetic resource. Here, we report the isolation and characteristics
      of a unique Arabidopsis mutant, hat1 (harmattan tolerant 1), which shows high
      tolerance to hot and dry air. Under normal growth conditions, the mutant does not
      differ in morphology and soil drought tolerance compared to the wild type. When
      subjected to high temperature (42 degrees C) and low humidity (10-15%), however,
      it could survive up to 6 days, while the wild type (Col-0) died after 24 h. The
      hat1 mutant also exhibits enhanced tolerance to soil drought, but only under
      xerothermic conditions. Mutant plants tightly close their stomata to retain water
      under xerothermic stress, and are more tolerant to high salinity at all
      developmental stages, accumulating less Na+ and more K+ than wild-type plants
      during NaCl treatment. Interestingly, hat1 plants are also ABA-hypersensitive.
      Genetic analysis revealed that the hat1 phenotype is caused by a dominant
      mutation at a single nuclear locus. Mapping studies indicate that Hat1 is located
      at an interval of 168 kb on chromosome 5 in which 21 genes are known to be
      regulated by diverse abiotic stresses. A mutant of this kind, to our knowledge,
      has not been previously reported. Thus, this report serves as a starting point in
      the genetic dissection of the plant response to xerothermic stress, and provides
      physiological and genetic evidence of the existence of a novel abiotic stress
      response pathway that is also ABA-dependent.

PMID- 16575592
TI  - Timecourse microarray analyses reveal global changes in gene expression of
      susceptible Glycine max (soybean) roots during infection by Heterodera glycines
      (soybean cyst nematode).
AB  - Changes in gene expression within roots of Glycine max (soybean), cv. Kent,
      susceptible to infection by Heterodera glycines (the soybean cyst nematode
      [SCN]), at 6, 12, and 24 h, and 2, 4, 6, and 8 days post-inoculation were
      monitored using microarrays containing more than 6,000 cDNA inserts. Replicate,
      independent biological samples were examined at each time point. Gene expression
      was analyzed statistically using T-tests, ANOVA, clustering algorithms, and
      online analytical processing (OLAP). These analyses allow the user to query the
      data in several ways without importing the data into third-party software. RT-PCR
      confirmed that WRKY6 transcription factor, trehalose phosphate synthase, EIF4a,
      Skp1, and CLB1 were differentially induced across most time-points. Other genes
      induced across most timepoints included lipoxygenase, calmodulin, phospholipase
      C, metallothionein-like protein, and chalcone reductase. RT-PCR demonstrated
      enhanced expression during the first 12 h of infection for Kunitz trypsin
      inhibitor and sucrose synthase. The stress-related gene, SAM-22, phospholipase D
      and 12-oxophytodienoate reductase were also induced at the early time-points. At
      6 and 8 dpi there was an abundance of transcripts expressed that encoded genes
      involved in transcription and protein synthesis. Some of those genes included
      ribosomal proteins, and initiation and elongation factors. Several genes involved
      in carbon metabolism and transport were also more abundant. Those genes included
      glyceraldehyde 3-phosphate dehydrogenase, fructose-bisphosphate aldolase and
      sucrose synthase. These results identified specific changes in gene transcript
      levels triggered by infection of susceptible soybean roots by SCN.

PMID- 16575593
TI  - Xylem-specific and tension stress-responsive coexpression of KORRIGAN
      endoglucanase and three secondary wall-associated cellulose synthase genes in
      aspen trees.
AB  - In nature, angiosperm trees develop tension wood on the upper side of their
      leaning trunks and drooping branches. Development of tension wood is one of the
      straightening mechanisms by which trees counteract leaning or bending of stem and
      resume upward growth. Tension wood is characterized by the development of a
      highly crystalline cellulose-enriched gelatinous layer next to the lumen of the
      tension wood fibers. Thus experimental induction of tension wood provides a
      system to understand the process of cellulose biosynthesis in trees. Since
      KORRIGAN endoglucanases (KOR) appear to play an important role in cellulose
      biosynthesis in Arabidopsis, we cloned PtrKOR, a full-length KOR cDNA from aspen
      xylem. Using RT-PCR, in situ hybridization, and tissue-print assays, we show that
      PtrKOR gene expression is significantly elevated on the upper side of the bent
      aspen stem in response to tension stress while KOR expression is significantly
      suppressed on the opposite side experiencing compression stress. Moreover, three
      previously reported aspen cellulose synthase genes, namely, PtrCesA1, PtrCesA2,
      and PtrCesA3 that are closely associated with secondary cell wall development in
      the xylem cells exhibited similar tension stress-responsive behavior. Our results
      suggest that coexpression of these four proteins is important for the
      biosynthesis of highly crystalline cellulose typically present in tension wood
      fibers. Their simultaneous genetic manipulation may lead to industrially relevant
      improvement of cellulose in transgenic crops and trees.

PMID- 16575594
TI  - Transgenic Medicago truncatula plants obtained from Agrobacterium tumefaciens 
      transformed roots and Agrobacterium rhizogenes-transformed hairy roots.
AB  - Medicago truncatula, barrel medic, is a forage crop that has been developed into
      a model legume. The development of new transformation methods is important for
      functional genomic studies in this species. Based on Agrobacterium tumefaciens
      mediated transformation of root explants, we developed an effective system for
      producing M. truncatula (genotype R108) transgenic plants. Among the four A.
      tumefaciens strains (AGL1, C58C1, EHA105 and LBA4404) tested, EHA105 and AGL1
      were most effective in regenerating transgenics. Callus induction frequency from
      root explants was 69.8%, and plantlet/shoot regeneration frequency was 41.3% when
      EHA105 was used. Transgenic nature of the regenerated plants was confirmed by PCR
      and Southern hybridization analyses. Progeny analysis revealed stable Mendelian
      meiotic transmission of transgenes. Because M. truncatula is particularly useful
      for the study of root endosymbiotic associations, we further developed a plant
      regeneration system from A. rhizogenes-transformed hairy roots of M. truncatula.
      Fertile true transgenic plants were regenerated from the hairy roots, thus
      allowing the assessment of gene functions at the whole plant level. Segregation
      analysis revealed that the hairy root genes could be segregated out in the
      progenies. By coupling A. rhizogenes-mediated hairy root transformation and the
      regeneration system reported here, once potential genes of interest are
      identified, the transformed hairy roots carrying such genes could be directly
      regenerated into plants for more detailed characterization of the genes.

PMID- 16575595
TI  - Identification of differentially expressed genes in seeds of two near-isogenic
      Brassica napus lines with different oil content.
AB  - The regulation of seed oil synthesis in rapeseed is largely unknown. In this
      study, we compared the gene expression during seed development between two lines
      of Brassica napus with a 10% difference in oil content. We isolated the immature
      seeds 15 and 25 days after flowering at periods preceding and including the major
      accumulation of storage oils and proteins. The differentially expressed gene
      clones between the two rape lines were isolated by subtractive suppression
      hybridization (SSH). All SSH clones were arrayed and screened by dot blot
      hybridization, followed by RT-PCR analysis for selected clones. A total of 217
      cDNA clones corresponding to 30 genes were found to have a high expression in
      seeds with high oil content. Six genes were highly expressed in seeds with low
      oil content. Northern blot and enzyme activity analysis demonstrated a change in
      expression pattern of several genes. The results provide information on gene
      encoding factors responsible for the regulation of oil synthesis. The possible
      role of these genes in seeds is discussed. The genes in this study may be
      suitable as novel targets for genetic improvement of seed oil content and may
      also provide molecular markers for studies of rape breeding.

PMID- 16575596
TI  - Na+/H+-transporter, H+-pumps and an aquaporin in light and heavy tonoplast
      membranes from organic acid and NaCl accumulating vacuoles of the annual
      facultative CAM plant and halophyte Mesembryanthemum crystallinum L.
AB  - Crassulacean acid metabolism (CAM) was induced in Mesembryanthemum crystallinum
      L. by either NaCl- or high light (HL)- stress. This generated in mesophyll cells
      predominantly of NaCl-stressed plants two different types of vacuoles: the
      generic acidic vacuoles for malic acid accumulation and additionally less acidic
      ("neutral") vacuoles for NaCl sequestration. To examine differences in the
      tonoplast properties of the two types of vacuoles, we separated microsomal
      membranes of HL- and NaCl-stressed M. crystallinum plants by centrifugation in
      sucrose density gradients. Positive immunoreactions of a set of antibodies
      directed against tonoplast specific proteins and tonoplast specific ATP- and PPi
      hydrolytic activity were used as markers for vacuolar membranes. With these
      criteria tonoplast membranes were detected in both HL- and NaCl-stressed plants
      in association with the characteristic low sucrose density but also at an unusual
      high sucrose density. In HL-stressed plants most of the ATP- and PPi-hydrolytic
      activity and cross reactivity with antibodies including that directed against the
      Na+/H+-antiporter from Arabidopsis thaliana was detected with light sucrose
      density. This relationship was inverted in NaCl-stressed plants; they exhibited
      most pump activity and immunoreactivity in the heavy fraction. The relative
      abundance of the heavy membrane fraction reflects the relative occurrence of
      "neutral" vacuoles in either HL- or NaCl-stressed plants. This suggests that
      tonoplasts of the "neutral" vacuoles sediment at high sucrose densities. This is
      consistent with the view that this type of vacuoles serves for Na+ sequestration
      and is accordingly equipped with a high capacity of proton pumping and Na+ uptake
      via the Na+/H+-antiporter.

PMID- 16575597
TI  - Protein interaction networks in plants.
AB  - Protein-protein interactions are fundamental to virtually every aspect of
      cellular functions. With the development of high-throughput technologies of both
      the yeast two-hybrid system and tandem mass spectrometry, genome-wide protein
      linkage mapping has become a major objective in post-genomic research. While at
      least partial "interactome" networks of several model organisms are already
      available, in the plant field, progress in this respect is slow. However, even
      with comprehensive protein interaction data still missing, substantial recent
      advance in the graph-theoretical functional interpretation of complex network
      architectures might pave the way for novel approaches in plant research. This
      article reviews current progress and discussions in network biology. Emphasis is
      put on the question of what can be learned about protein functions and cellular
      processes by studying the topology of complex protein interaction networks and
      the evolutionary mechanisms underlying their development. Particularly the
      intermediate and local levels of network organization--the modules, motifs and
      cliques--are increasingly recognized as the operational units of biological
      functions. As demonstrated by some recent results from systematic analyses of
      plant protein families, protein interaction networks promise to be a valuable
      tool for a molecular understanding of functional specificities and for
      identifying novel regulatory components and pathways.

PMID- 16575598
TI  - What predicts outcome in non-operative treatments of chronic low back pain? A
      systematic review.
AB  - Systematic reviews have shown that as non-operative treatments exercise,
      behavioural and multimodal treatment programs are effective for chronic low back
      pain. There is, however, a lack of knowledge concerning the association between
      changes in treatment process variables and changes in outcome for the three
      treatment forms. The objective of this systematic review was to evaluate which
      changes in treatment process variables predict outcome of exercise, behavioural
      and multimodal treatment of chronic low back pain. Medline, Embase and PsychInfo
      were systematically searched. A descriptive analysis was used to summarize the
      results regarding the outcomes pain, disability and return to work (RTW). 13
      studies were identified. The results showed that functional coping mechanisms and
      pain reduction were associated with a decrease in disability and increase in RTW,
      and physical performance factors were not. Related to pain reduction decreases in
      disability, functional coping mechanisms as well as physical performance factors
      were associated. Strong conclusions cannot be drawn from this review, because of
      the heterogeneity and the limited number of studies. The results of this review
      raise the question if changes in behavioural variables and reductions of
      disability which facilitate an improvement in function, may be more important
      than physical performance factors for successful treatment of chronic low back
      pain. This is relevant for the refinement of future treatment programs.

PMID- 16575600
TI  - [Miller Fisher syndrome: case report and review with discussion of differential
      diagnosis and nosology].
AB  - We report a 52-year-old patient with Miller Fisher syndrome and discuss
      Wernicke's encephalopathy as one important differential diagnosis. This article
      focuses on diagnostic criteria and possible nosological relations between Miller
      Fisher syndrome, Guillain-Barre syndrome with ophthalmoplegia, Bickerstaff's
      brainstem encephalitis, and acute ophthalmoparesis without ataxia.

PMID- 16575599
TI  - [Medically induced myopathia].
AB  - Muscular side effects of various anesthetics, analgetics, antibiotics,
      antihistaminic drugs, antiretrovirals, cardiotropics, immunosuppressants, lipid
      lowering drugs, psychotropic drugs, anticancer drugs, and other substances are
      more frequent than assumed and are easily overlooked. Clinically, muscular side
      effects manifest as fatigue, myalgias, persistent or transient weakness,
      stiffness, intolerance to exercise, psychomotor slowing, muscle cramps, wasting,
      dyspnea, dysphagia, fasciculations, reduced tendon reflexes, impaired
      consciousness, myoglobinuria, renal failure, or hyperthermia. Diagnosis of these
      drug-induced myopathies is based on history, clinical neurologic examination,
      blood work, urine analysis, repetitive stimulation, electromyography, and muscle
      biopsy. A drug which induces muscular side effects should never be given again.
      Particularly in patients suffering from primary myopathy, myotoxic drugs should
      be applied with caution. The drugs which most frequently induce muscular side
      effects are steroids, statins, fibrates, antiretrovirals, immunosuppressants,
      colchicine, amiodarone, and anticancer drugs. Many drugs exhibit their myotoxic
      potential only in combination with other drugs or premorbid pathologic myogenic
      conditions.

PMID- 16575601
TI  - [Retropharyngeal inflammation presenting as meningitis: an important differential
      diagnosis in clinical neurology].
AB  - We report three patients who presented with occipital headache, neck pain,
      meningism, fever, and inflammatory findings in laboratory tests. Lumbar puncture
      for suspected meningitis revealed normal CSF findings in all patients. Magnetic
      resonance imaging demonstrated inflammation of the deep neck space, leading to
      the final diagnosis of retropharyngeal abscess.

PMID- 16575603
TI  - [Three-dimensional analysis of the foot following implantation of a HINTEGRA
      ankle prosthesis: evaluation with the Heidelberg foot model].
AB  - Detailed foot kinematics after total ankle replacement has not yet been
      investigated. In this study 11 patients with unilateral Hintegra ankle prosthesis
      were analysed with the Heidelberg Foot Model. This model measures the kinematics
      of the fore-, mid- and hindfoot in three clinical planes. Moreover, the kinetics
      of the hip, knee and ankle was captured. A diminished ROM was found in all foot
      segments investigated. The timing of the kinematics between sound and involved
      side appeared similar. A limitation in the hindfoot mobility, as experienced
      after ankle arthrodesis, was not observed. However, a careful hindfoot alignment
      is essential for optimal foot function, and previous malalignments should be
      corrected. Concerning the kinetics, the replaced ankle showed a decreased power
      generation compensated by an increase in power in the ipsilateral knee. For a
      more detailed evaluation, further studies are required which include pre- and
      postoperative data and also take into account different types of prostheses.

PMID- 16575604
TI  - Defecation mechanisms after anterior resection with J-pouch-anal and side-to-end
      anastomosis in dogs.
AB  - BACKGROUND: Colonic J-pouch-anal anastomosis or colonic side-to-end anastomosis
      is the reconstruction of choice after low anterior resection. However, the
      mechanisms of defecation after both reconstruction forms are still speculative.
      METHODS: Low anterior rectal resections were performed in 12 dogs with six
      colonic J-pouch-anal (pouch) and six coloanal side-to-end (SE) reconstructions.
      Four months postoperative stool frequency, intestinal transit time, and neorectal
      compliance were determined by radiography and barostat. Defecation mechanisms
      were evaluated radiographically during expulsion of artificial stool. RESULTS:
      One dog with pouch reconstruction could not be evaluated due to an anastomotic
      leak, while the others had uncomplicated course. Spontaneous stool frequency was
      significantly increased with both reconstruction methods (control 2.0+/-0.9,
      pouch 2.7+/-1.2, SE 3.3+/-0.9 day; p<0.05). Intestinal transit time was
      significantly higher with pouch reconstruction due to storage of stool in the
      pouch and the descending colon compared to SE (control 760+/-82, pouch 592+/-97,
      SE 550+/-87 min; p<0.05). Compliance and functional capacity were higher in pouch
      than in side-to-end reconstructions (pouch 5.0+/-0.7 ml/mmHg, 124+/-23 ml; SE
      2.7+/-0.3 ml/mmHg, 92+/-24 ml; p<0.05). During defecation, there were no
      contractions of the pouch detectable. CONCLUSIONS: The colonic J-pouch
      reconstruction results in better functional outcome than side-to-end coloanal
      anastomosis. Our results show that pouch evacuation is passive and independent
      from pouch motility. The functional principle of the colonic J-pouch is not its
      reservoir function but a delay of colonic motility.

PMID- 16575605
TI  - More than just skin deep!: a report on a family with Muir-Torre syndrome.

PMID- 16575606
TI  - Diagnostic and surgical approaches in hilar cholangiocarcinoma.
AB  - Hilar cholangiocarcinoma is a rare tumor. Surgery remains the only treatment to
      prolong survival. There is a correlation between the extent of diagnostic work-up
      and the achieved resection rates. Moreover, diagnostic work-up may contribute to
      an improvement of the surgical technique. Due to the perihilar fibrosis, the
      extent of the central lesion may be overestimated, which may lead to exclude the
      patient from potentially curative surgery. En bloc resection is requested to
      achieve tumor-free resection margins. The prognosis of the patients treated with
      surgery is strongly influenced by negative resection margins. According to our
      experience, 5-year survival of 78/111 patients with tumor resection (resection
      rate 71%) has been 30%. Forty-eight percent of the patients with curative en bloc
      resection of tumor and liver survived for more than 5 years. Perioperative
      mortality was 5.1%. The available data are supposed to reflect the results of
      centers with high caseload and not the general situation.

PMID- 16575607
TI  - Subdivision of the accessory olfactory bulb in the Japanese common toad, Bufo
      japonicus, revealed by lectin histochemical analysis.
AB  - Lectin binding patterns in the olfactory bulb of the Japanese common toad, Bufo
      japonicus, were examined using 21 types of lectin. Ten out of 21 lectins, WGA, s
      WGA, LEL, STL, DBA, VVA, SJA, RCA-I, PNA, and PHA-L, stained the olfactory nerve,
      the glomeruli in the main olfactory bulb (MOB), the vomeronasal nerve, and the
      glomeruli in the accessory olfactory bulb (AOB). The binding patterns of LEL,
      STL, DBA, and PHA-L subdivided AOB glomeruli into rostral and caudal regions,
      where LEL, STL, and DBA stained the rostral region more intensely than the caudal
      region, and PHA-L had the opposite effect. Another lectin, BSL-I, stained both
      AOB glomeruli and the vomeronasal nerve, but not MOB glomeruli or the olfactory
      nerve. This is the first report of histological subdivision in the AOB of an
      amphibian, which suggests that the AOB development in Bufo may be unique.

PMID- 16575608
TI  - Favourable mid-term results of the VerSys CT polished cemented femoral stem for
      total hip arthroplasty.
AB  - We evaluated the mid-term clinical and radiographical performance of a cohort of
      patients who underwent primary total hip replacement with a modern, forged cobalt
      chrome, polished cemented femoral stem with proximal and distal centralisation.
      Sixty-seven patients with 73 hybrid total hip replacements were followed up
      clinically and radiographically for an average of 6.1 years (4-8.5). No patient
      was lost. No hips required revision, and all stems are radiographically well
      fixed. Four hips developed localised osteolysis: one at the site of a proximal
      periprosthetic fracture, another at the level of a lateral femoral window of a
      previous core decompression, the third at the mid third of the femoral component,
      and the fourth on the greater trochanter, associated with accelerated
      polyethylene wear. This modern polished stem yielded excellent, predictable
      clinical and radiographic results at an intermediate follow-up.

PMID- 16575610
TI  - Pentosidine in osteoarthritis: HPLC determination in body fluids and in tissues.
AB  - The aim of this study is to determine whether and to which extent pentosidine
      (PEN) is influenced in the case of advanced osteoarthritis (OA) in urine and in
      some tissues. Reverse phase HPLC method for PEN determination with fluorescence
      monitoring was utilized. Urinary pentosidine (U-PEN) and pyridinoline (U-PD) were
      determined in the group (N=67, age 67.1+/-11.7 years) in patients with OA before
      and after surgery (knee or hip replacement), and in healthy age-matched controls
      (N=18, age 67.0+/-6.0 years). Cartilage, synovial membrane and granulation tissue
      were also treated. In OA group significantly higher (P<0.001) U-PEN
      concentrations before (7.5+/-5.1 nmol/mmol creat.) and after (4.9+/-2.6 nmol/mmol
      creat.) surgery were found. U-PD was not significantly different between the
      groups (62.5+/-33.0 and 55.0+/-29.51 nmol/mmol creat., respectively), but
      differed significantly (P<0.0002 and P<0.01) from healthy subjects (40.2+/-16.5
      nmol/mmol creat.). In the newly formed granulation tissue, PEN concentrations are
      significantly lower than in cartilage and in synovial tissues.

PMID- 16575612
TI  - [Stem cell therapy. Biology of hematopoietic stem cells].
AB  - In recent years much progress has been made in the understanding of the biology
      of hematopoietic stem cells (HSC) and their involvement in normal blood cell
      development. Using immunophenotyping it is possible, to enrich HSC, however, so
      far we are not able to positively select HSC. For the identification,
      characterization and quantification of HSC it is necessary to use functional
      assay systems, such as xenotransplantation models. HSC from bone marrow,
      peripheral blood and in some cases also cord blood have been used for years in
      transplantation settings especially in patients with leukemia. A better
      understanding of the mechanisms underlying stem cell regulation as well as stem
      cell self renewal would have clinical implications e. g. for clinical
      transplantation strategies. A number of hematological diseases such as chronic
      myeloid leukemia originates from a malignant transformed HSC. A better
      understanding of the biology of normal as well as malignant HSC is therefore
      crucial not only for a better understanding of the disease, but also for the
      development of strategies aiming at the discrimination of normal and malignant
      stem cell candidates and the development of therapies targeting the leukemic stem
      cell.

PMID- 16575611
TI  - [Therapy of diabetes mellitus. Pancreas transplantation, islet transplantation,
      stem cell and gene therapy].
AB  - The long-term normalization of glucose metabolism - a prerequisite for the
      prevention of secondary complications in patients with diabetes mellitus - is
      only possible by transplantation of a whole pancreas or a reasonable number of
      islets. An absolute indication for pancreas grafting is given in type 1 diabetic
      patients with end-stage renal disease. The 1-year survival after simultaneous
      kidney/pancreas transplantation is, according to the international registry, 94
      100% for patients, 89-92% for kidneys and 85-87% for the pancreas. The high
      success rate with long lasting normalization of glucose metabolism leads to a
      stabilization and/or amelioration of secondary complications, to an increase in
      quality of life and, most importantly, to a significant reduction in mortality
      when compared to diabetic kidney recipients. The indications for islet
      transplantation are similar to those for pancreatic grafting. Islet grafting is
      only a minor surgical procedure, but islet isolation is difficult. The 1-year
      survival for the recipients is 98%, for the islets 82% and for insulin
      independency 42%. There is a significant decline of islet function to 10% 5 years
      after transplantation. Stem cell therapy would provide a definitive treatment
      solution not only for patients with type 1 diabetes. So far, this therapeutic
      option is still at an early stage of development.

PMID- 16575613
TI  - [33 year old Libanese woman with recurrent haemoptysis and cystic lesion of the
      lung].
AB  - A 33 year old woman from Lebanon presented with recurrent hemoptysis, subfebrile
      temperature, dyspnoe in stress, fatigue, weight loss, and pruritus. Serological
      tests and results from chest X-ray and computer tomography revealed cystic
      echinococcosis with pulmonary involvement. After refusal of surgical therapy a
      medical treatment with albendazole was implemented. Two months after the start of
      the therapy only a small fibrotic residuum in the lung was seen. A spontaneous
      healing success seems unlikely because of the duration of the pulmonary cyst and
      the progressive symptoms before treatment.

PMID- 16575615
TI  - Impact factors revisited.

PMID- 16575614
TI  - [Postoperative pulmonary complications: prophylaxis after noncardiac surgery].
AB  - Postoperative pulmonary complications are a major problem after upper abdominal
      or thoracoabdominal surgery. They lead to a prolonged ICU stay as well as
      increased costs and are one of the main causes of early postoperative mortality.
      Even after uncomplicated operations, postoperative hypoxemia occurs in 30-50% of
      patients. Acute respiratory failure involves a disturbance in gas exchange. The
      mortality ranges from 10 to 60% according to the severity of respiratory failure.
      The most important complications are interstitial and alveolar pulmonary edema,
      atelectasis, postoperative pneumonia, hypoventilation, and aspiration.
      Preoperative optimization, postoperative prophylaxis according to a stepwise
      approach, and early mobilization decrease the rate of complications.

PMID- 16575617
TI  - Bone mineral density and estimated height loss based on patients' recalls.
AB  - INTRODUCTION: Height loss has been shown to be an indicator of incident vertebral
      fractures. However, the relationship between height loss and bone mineral density
      (BMD) in different skeletal regions, as well as the power of human memory in
      estimation of height loss across the life span, has not yet been established.
      Given that the variation in BMD between populations is substantially less than
      the variation in fracture risk, we studied the relationship between height loss
      based on patient's recalls and BMD in Iranian men and women of all ages. METHODS:
      Randomized clustered sampling from all regions of Tehran was performed to recruit
      the study population. Participants were asked about their maximum recalled
      previously measured height, if they were confident. In the 457 participants
      included, the difference between the participants' maximum recalled and current
      measured height was calculated. RESULT: L1-L4 lumbar BMD, femoral neck BMD, and
      young adjusted T-scores were significantly lower in the group of participants
      with estimated height reduction of greater than 5 cm. In simple linear regression
      analysis, height loss was a significant predictor of femoral neck T-score
      (standardized beta coefficient=-0.15; p0.003) and L1-L4 lumbar T-score (beta=
      0.08; p0.048). After adjustment for age, gender, and weight, height loss remained
      a significant predictor for femoral neck T-score (beta=-0.078; p0 .043). In
      multivariate models for lumbar T-score, height loss was an independent predictor
      only in participants equal to or younger than 50 years of age (beta=-0.144;
      p0.033). CONCLUSION: Higher estimated height loss according to patients' recalls
      was an indicator of lower BMD in our sample. Especially in the femoral neck
      region, this factor might be considered as a substitute case-finding tool for low
      BMD. Considering relatively young nature of our study group and biological
      differences between populations, our findings need to be validated in future
      prospective studies.

PMID- 16575619
TI  - Immunohistochemical expression of p16, p53, and p63 in colorectal adenomas and
      adenocarcinomas.
AB  - PURPOSE: The aim of this study was to investigate the immunohistochemical
      expression of p16, p53, and p63 proteins according to some pathologic parameters
      related to colorectal adenomas and adenocarcinomas such as grade of dysplasia and
      histologic type. METHODS: Immunohistochemistry with the antibodies p16, p53, and
      p63 was performed in tubular, tubular-villous, and villous adenomas (n = 30) and
      in well, moderately, and poorly differentiated adenocarcinomas (n = 30). The p63
      positive cases were submitted to double immunolabeling with the cytokeratin 5
      (CK5). RESULTS: The p16 and p53 labelings were observed in some adenomas and
      adenocarcinomas but without any association with p63 expression, histologic type,
      or grade of differentiation of the neoplasm. P63 expression was found mainly in
      the villous adenomas and in the poorly differentiated adenocarcinomas. The poorly
      differentiated adenocarcinomas also exhibited coexpression of CK5 and p63.
      CONCLUSIONS: Despite both p16 and p53 having been detected in colorectal
      neoplasms, they were not related to the different histologic variables nor to the
      expression of p63. However, p63 expression was closely associated with villous
      adenomas and poorly differentiated adenocarcinomas. Thus, p63 may represent a
      marker of poor differentiation in colorectal neoplasms. The coexpression of p63
      and CK5 observed in this study could be related to divergent differentiation
      during the development of colorectal cancer, although further studies are
      warranted to refine the understanding of this process.

PMID- 16575620
TI  - Impact of new technologies on the clinical and functional outcome of Altemeier's
      procedure: a randomized, controlled trial.
AB  - PURPOSE: A randomized study was performed to assess whether new technologies
      offer advantages over the conventional technique on the clinical and functional
      outcome of patients with full-thickness rectal prolapse and fecal incontinence,
      submitted to Altemeier's procedure with levatorplasty. METHODS: Between January
      1999 and December 2003, 58 patients (55 females; mean age, 70.9 +/- 11.3 years)
      with full-thickness rectal prolapse were evaluated with continence score,
      colonoscopy, anorectal manometry, anal electromyography, and sacral reflex
      latency; 40 of them were selected and randomly assigned to two groups: 20
      patients (Group 1; 19 females, 73.4 +/- 10.4 years) were submitted to a
      conventional operation with monopolar electrocautery and handsewn anastomosis,
      and 20 (Group 2; 18 females, 71.5 +/- 12.2 years) using harmonic scalpel and
      circular stapler. Patients were followed up with clinical examination, anorectal
      manometry, and anal electromyography, with mean follow-up 29.3 +/- 8.5 and 27.5
      +/- 9.2 months in Groups 1 and 2, respectively. RESULTS: Operative time, blood
      loss, and hospital stay were significantly reduced in Group 2 (P < 0.001),
      whereas no differences were found in pain score, time to return to normal
      activity, morbidity, and mortality. Complications were two (10 percent) stenosis
      in Group 1. Fecal continence score significantly improved in both groups (P <
      0.01), whereas anorectal manometry and neurophysiologic data were not
      significantly modified by the operation. Recurrence rates were 15 and 10 percent
      in Groups 1 and 2, respectively (P= not significant). CONCLUSIONS: The clinical
      and functional long-term results of perineal rectosigmoidectomy with
      levatorplasty are not influenced by surgical instruments and type of coloanal
      anastomosis. The clinical relevance of the short-term results in high-risk
      patients should be specifically investigated.

PMID- 16575621
TI  - Early prediction of anastomotic leak in colorectal cancer surgery by intramucosal
      pH.
AB  - PURPOSE: Adequate oxygenation is necessary for anastomotic healing, and ischemia
      has been found to be one of the most important factors in anastomotic leakage.
      This study was designed to assess the value of early postoperative intramucosal
      pH measurements for the prediction of anastomotic leakage in patients with
      colorectal anastomosis. METHODS: A prospective study of 90 patients with rectal
      or sigmoid cancer with primary anastomosis was conducted. In all patients
      intramucosal pH was determined by using tonometry at the anastomotic and gastric
      levels during the first 24 and 48 hours postoperatively. Seven other variables
      also were tested by univariate and multivariate analysis for any association with
      anastomotic leakage. RESULTS: The rate of clinical anastomotic leakage was 6.6
      percent. Multivariate analysis showed that only the intramucosal pH at the
      anastomosis was an independent factor for the development of anastomotic leakage.
      The risk of leakage was 22 times higher in patients with an anastomotic
      intramucosal pH < 7.28 in the first 24 hours after surgery. CONCLUSIONS:
      Measurement of anastomotic intramucosal pH in the early postoperative period can
      more accurately predict the risk of anastomotic leakage and benefit those
      patients who would need additional measures to improve the viability of the
      anastomosis.

PMID- 16575622
TI  - The effect on morbidity of mesentery lengthening techniques and the use of a
      covering stoma after ileoanal pouch surgery.
AB  - PURPOSE: A tension-free anastomosis in a restorative proctocolectomy requires
      sufficient length of small-bowel mesentery. To ensure adequate length, it has
      been proposed that the superior mesenteric artery be divided and the right colon
      marginal vascular arcade be preserved. This study was designed to evaluate the
      influence of mesenteric lengthening techniques on the need for a stoma and on
      early outcomes after restorative proctocolectomy. METHODS: Records of patients
      who had a restorative proctocolectomy between January 1998 and October 2003 were
      reviewed. Patient and disease characteristics, operative techniques and findings,
      the need for a stoma, and postoperative complications were recorded. RESULTS: In
      one patient a restorative proctocolectomy was not possible. The remaining 220
      patients were divided into two groups: Group A (inflammatory bowel disease; n =
      123) and Group B (noninflammatory bowel disease; n = 97). Sixty-nine patients
      (31.4 percent) had major comorbidities. A lengthening technique was performed in
      120 patients (54.5 percent) by dividing the ileocecal artery (n = 37) or the
      superior mesenteric artery (n = 88); 5 patients had only the marginal vascular
      arcade preserved. An ileostomy was not required in 116 patients (52.7 percent).
      In multivariate analysis, in Group B the only surgical variable influencing the
      need for an ileostomy was preservation of the marginal vascular arcade (50 vs.
      14.7 percent; P < 0.0005). Complications occurred in 41 patients (18.6 percent),
      more frequently for those in Group A and for patients receiving steroids (23.6
      vs. 12.4 percent, P = 0.012; 10.4 vs. 6.8 percent, P = 0.0172). CONCLUSIONS: The
      use of mesentery lengthening techniques allows a restorative proctocolectomy to
      be performed in almost all patients without increasing morbidity and may reduce
      the number of covering stomas. Because division of the ileocecal and/or superior
      mesenteric arteries may be required, preservation of the marginal vascular arcade
      is essential whenever possible.

PMID- 16575623
TI  - [Autonomic nervous system: has it been greatly ignored?].

PMID- 16575624
TI  - [Utility of the study of the vegetative nervous system in the differential
      diagnosis between Parkinson's disease and multiple system atrophy].
AB  - INTRODUCTION: The aim of this study is to show if the exploration of the
      autonomic nervous system is useful to improve the specificity of clinical
      criteria of Parkinson's Disease (PD) and Multiple System Atrophy (MSA). PATIENTS
      AND METHODS: 20 patients with PD and 13 patients with MSA were studied. After 12
      hours in off medication, NE and GH were measured in supine position and NE after
      5 minutes standing. Later, GH levels were recorded at 15, 30, 45 and 60 minutes
      after a dose of 0.005 mg/kg of apomorphine. Finally, analysis of the symptoms of
      autonomic dysfunction and levodopa test were carried out. RESULTS: Sympathetic
      response to postural changes was significantly higher in patients with PD (NE
      increase in relation to basal: PD: 170.90 +/- 110.08 pg/ml; MSA: 91.33 +/- 73.79
      pg/ml; p = 0.029). No differences were found in the response of GH to apomorphine
      (GH peak at 45 minutes: PD: 2.37 +/- 2.7 ng/ml; MSA: 1.69 +/- 1.90 ng/ml; ns).
      The symptoms of autonomic dysfunction were more frequently in patients with MSA.
      The stridor was specific to MSA. Improvement in motor scores in the levodopa test
      was higher in patients with PD (PD: 39.7 %; MSA: 17.89; p = 0.019). DISCUSSION:
      Sympathetic response to postural changes, description of symptoms of autonomic
      dysfunction, and motor response to levodopa test are useful tools in order to
      improve specificity of the diagnostic criteria of PD and MSA. The GH test with
      apomorphine was not useful for a differential diagnosis.

PMID- 16575625
TI  - [Verbal fluency tasks in a Spanish sample of young adults (20-49 years of age):
      normative data of clustering and switching strategies].
AB  - INTRODUCTION: The aim of this study is to establish normative data on
      phonological and semantic verbal fluency tests, measuring total production of
      words, clusters and switching of words in a healthy young adult Spanish
      population. MATERIAL AND METHODS: We assessed 53 healthy adults between 20-49
      years old (32.8 +/- 9.5) with 8-18 years of formal education (9 +/- 3.3 years).
      The semantic fluency category included: animals, fruits, clothes and the initial
      letters F, A, S in 1 minute of time. Clustering and switching strategies were
      examined and scored according to a protocol elaborated ad hoc by the authors.
      Pearson correlations between number of "clusters", "switching" and total number
      of words was used and we evaluated the possible influence of age, years of
      schooling and gender in each one of the categories in 1 minute and in intervals
      of 15 seconds. RESULTS: The variable years of formal education was the only
      demographical factor that significantly influenced semantic verbal fluency (r =
      0.43; p = 0.04). Switching and clustering were positively correlated with the
      number of words generated. Clustering was highly correlated with total number of
      words generated on semantic fluency (r = 0.846; p < 0.01). In contrast, switching
      was more highly correlated than clustering with total number of words generated
      on phonemic fluency (r = 0.864; p < 0.01). CONCLUSIONS: Rules for scoring
      switching and clustering in our population are provided. Optimal fluency
      performance requires some type of balance between clustering and switching
      strategies and should be taken into account in studies regarding verbal fluency.

PMID- 16575626
TI  - [Experience with intranasal zolmitriptan in cluster headache].
AB  - INTRODUCTION: The objective is to analyse our experience with the new intranasal
      formulation of zolmitriptan 5 mg in the symptomatic treatment of cluster headache
      in daily clinical practice. PATIENTS AND METHODS: We collected a total of 18
      patients with cluster headache and experience with intranasal zolmitriptan; 17
      had used subcutaneous sumatriptan and 8 oral triptans. The main reasons for
      trying intranasal zolmitriptan were: poor tolerability in 12 patients and
      insufficient efficacy in 6. RESULTS: Among the 17 patients experienced in
      subcutaneous sumatriptan, 12 (71 %) preferred nasal zolmitriptan, 2 (18 %)
      subcutaneous sumatriptan and 2 (12 %) did not express any preference. The reasons
      for preferring intranasal zolmitriptan were: higher convenience (n = 6), better
      tolerability (n = 5), lower price (n = 2) and higher efficacy (n = 1). Seven out
      of the 8 patients who had taken oral triptans preferred nasal zolmitriptan, in
      all cases due to higher subjective efficacy. A total of 11 patients showed
      efficacy within 30 minutes. Only 3 patients referred to adverse events, always
      mild. CONCLUSIONS: The 5 mg nasal formulation of zolmitriptan is a potential new
      option for the symptomatic treatment of cluster headache. This formulation should
      be considered in patients with poor tolerability to subcutaneous sumatriptan and
      in those attacks where quick access to inhaled oxygen is not possible. These
      results suggest that a controlled trial with nasal zolmitriptan in this
      indication would be worthwhile.

PMID- 16575627
TI  - [Chagas' disease and ischemic stroke].
AB  - American trypanosomiasis, known as Chagas' disease (CD) is a major Public Health
      problem in South America. Chronic cardiomyopathy is the most common clinical form
      of CD. Chagasic cardiomyopathy affects about 30 % of CD patients, and its
      manifestations begin on average 10-40 years after the initial infection. Chagas'
      cardiomyopathy is characterized by congestive heart failure, sudden cardiac
      death, intraventricular conduction defects, arrhythmias and thromboembolism. The
      relationship between Chagas' cardiomyopathy and ischemic stroke was reviewed.
      Significant variables that predict ischemic stroke in chagasic patients have been
      identified: apical aneurysm, cardiac insufficiency and cardiac arrhythmia.
      Prevalence of apical aneurysm in CD stroke patients has been estimated in 37%.
      The diagnosis of CD may be established after stroke presentation in at least 40%
      of patients. Chagasic cardiomyopathy should be included in the differential
      diagnosis of the etiology of stroke, being a potential source of cardioembolic
      stroke.

PMID- 16575628
TI  - [Vertigo as initial symptom of a myxoma in a young male].

PMID- 16575629
TI  - [Total dream loss secondary to left temporo-occipital brain injury].
AB  - INTRODUCTION: Recently the case of a woman who reported cessation of dreaming
      after a bilateral PCA stroke but without REM sleep loss has been reported,
      suggesting that deep bilateral occipital lobe damage including the right inferior
      lingual gyrus may represent the "minimal lesion extension" necessary for dream
      loss. CASE REPORT: We report the case of a 24-year-old man who ceased dreaming
      after a unilateral left temporo- occipital hematoma. The polysomnographic
      characteristics in rapid eyes movements (REM) sleep were otherwise normal.
      CONCLUSION: Our patient demonstrates that a unilateral left temporo-occipital
      injury could be sufficient for losing dreams.

PMID- 16575630
TI  - [Transient ischemic attack: the only presenting syndrome of dural sinus
      thrombosis].
AB  - INTRODUCTION: Intracranial hypertension (ICHT) is the most frequent presenting
      syndrome of dural vein sinus thrombosis (CVT). A transient ischemic attack as an
      acute mode of onset is exceptional. CASE REPORT: A right handed, forty years old
      man with a medical history of recurrent headaches, microcephalia and
      calcifications in his brain, presenting to the emergency department with left
      paresis that lasted a few minutes and with a complete recovery. The cerebral and
      neck magnetic resonance (MR) including MR angiography showed superior sagittal
      sinus, both transverse sinuses and right sigmoid sinus thrombosis with an
      increase in size of superficial cerebral venous that drained to the left sigmoid
      sinus. There was no evidence of intracranial dural malformations. The cerebral MR
      did not show any abnormal parenchymal enhancement (edema, arterial or venous
      infarctions, hemorrhage) including diffusion-weighted IMR. The digital
      subtraction angiography (ADC) confirmed the same findings as the MR angiography.
      The diagnosis was a chronic CVT. We studied stroke in a young adult and we did
      not find other irregularities. The neurological examination was normal when the
      patient left the hospital with an antiplatelet drug. CONCLUSIONS: Focal
      neurological deficit is an exceptional event of a chronic vein sinus thrombosis
      during follow-up. Isolated cases regarding an acute time course have been
      described. The interest of this case lies in the fact that venous sinus
      thrombosis rarely has transitory focal deficit in its course and we found no such
      description as onset symptoms.

PMID- 16575631
TI  - [Light-induced amaurosis fugax].
AB  - INTRODUCTION: Internal carotid artery atherosclerotic disease may present with a
      wide variety of ipsilateral ocular symptoms and signs that can herald a
      devastating stroke. Asymptomatic retinal emboli, transient monocular visual loss
      (also known as amaurosis fugax) and central retinal artery occlusion are the most
      common. CLINICAL CASE: A 66-year-old man presented several spells of monocular
      light-induced amaurosis fugax related to a severe carotid occlusive disease.
      Ancillary tests showed an exhausted cerebrovascular reactivity and visual evoked
      potentials demonstrated an increased latency. Following a carotid endarterectomy
      the patient remained asymptomatic and ancillary tests normalized. DISCUSSION: Our
      report supports the theory that light-induced amaurosis fugax occurs on a
      hemodynamic basis. A prompt recognition of this symptom is critical since
      symptomatic severe carotid stenosis implies a high risk of ipsilateral stroke.

PMID- 16575632
TI  - [Reflections on Pedro Lain Entralgo and Juan Rof Carballo].

PMID- 16575635
TI  - [Use of vacuum therapy in a huge arterialized venous flap to reconstruct a
      complete avulsion of a thumb].
AB  - Arterialized venous flaps are normally raised from the anterior and distal third
      of the forearm by integration of a venous pathway. Basically, they are composed
      of skin, subcutaneous tissue, and subdermal venous plexus. Following
      transposition to the recipient site one vein is linked to a nourishing artery
      while the other veins are connected to one or more regional veins. The atypical
      blood perfusion and the delayed opening of intervenous shunts may result in
      edema, epidermolysis, or even some degree of skin necrosis that disappear during
      subsequent treatment. We report the salvage of an atypically raised oversized
      arterialized venous flap for total soft tissue reconstruction in a complete
      avulsion of a thumb. By applying V.A.C. therapy atypical perfusion and early
      intervenous shunt formation was treated successfully, resulting in stable healing
      and survival of the flap.

PMID- 16575637
TI  - [Successful vacuum therapy of a large defect on the scalp].

PMID- 16575636
TI  - [Vacuum assisted closure (V.A.C.) therapy is an essential tool for treatment of
      complex defect injuries of the upper extremity].
AB  - INTRODUCTION: Complex injuries of the upper extremity remain a therapeutic
      challenge. The prognosis of the damaged extremity is often limited by soft tissue
      defects. Vacuum Assisted Closure (V.A.C.) therapy facilitates temporary coverage
      of soft tissue defects prior to surgical reconstruction. METHODS: In a
      retrospective study all patients with complex defect injuries of the upper
      extremity that were treated by V.A.C. prior to reconstruction between August 2003
      and September 2005 were analyzed. RESULTS: 7 patients (6 male, 1 female, 14-70
      years) were included in the study. The patients suffered from subtotal upper arm
      (n = 1) and forearm (n = 1) amputation, complex multilevel amputation injury of
      the forearm (n = 1), slash wound of the forearm with skin defect and
      discontinuity of all volar structures (n = 1), complex open forearm fractures
      with skin and soft tissue defects (n = 2), and almost complete necrosis of the
      flexor compartment following distal radius and proximal ulnar fracture and
      compartment syndrome (n = 1). Stabile defect coverage was achieved in all
      patients following V.A.C. therapy by myocutaneous free flaps (n = 2), split
      thickness skin grafts (STSG) (n = 2), sequential secondary suture (n = 1), and
      STSG + secondary suture (n = 2). Wound conditions improved significantly under
      V.A.C. therapy. 5 patients reported pain relief following induction of V.A.C.
      therapy. Due to reduction of tissue oedema secondary suture was facilitated in 3
      patients. DISCUSSION: V.A.C. therapy represents an essential tool for treatment
      of complex injuries of the upper extremity with extended soft tissue defects.
      Decreased frequency of dressing changes as well as reduced tissue oedema
      considerably improved patient's comfort. Posttraumatic compartment syndrome or
      skin necrosis, which are often associated with macro amputations of the upper
      extremity, are efficiently treated with V.A.C., and secondary sutures may be
      performed despite initial skin defects.

PMID- 16575638
TI  - [Vacuum-assisted closure (V.A.C.) of disastrous wound conditions in Madelung
      disease].
AB  - INTRODUCTION: A 54 year old patient presented with a Madelung disease.
      Symmetrically fatty deposits were present on both upper arms, at the abdomen and
      both thighs. Dermatitis was seen in the axillary fold at the skin bearing
      surfaces. Shoulder movement was impaired. Liposuction of both upper arms has
      already been performed, but no significant improvement was obtained. METHODS AND
      RESULTS: We performed a dermolipectomy of both upper arms. Postoperatively the
      patient suffered from a severe wound dehiscence with fulminant wound infection
      and septic clinical condition. Because of the large wound surface ((1/3) of the
      upper arm circumference) anemia occurred and had to be treated with blood
      transfusions. Wound exsudation caused a general hypoproteinemia. Multiple
      surgical debridements were necessary in order to clean the wound from necrotic
      tissue and afterwards moist dressings were applied. Furthermore the patient
      received intravenous antibiotic treatment. After stabilisation of the general
      condition of the patient and the wound situation a polyvinyl sponge and a vacuum
      sealing were applied and continuous suction was performed (125 mm Hg). This
      resulted in a significant improvement of the wound situation in regards to wound
      cleaning, induction of granulation tissue, diminished wound size, reduction of
      oedema and pain reduction. After four weeks of vacuum therapy defect coverage was
      possible and split thickness skin grafting was performed. The skin graft was
      attached to the wound using a vacuum-dressing. After removal of the vacuum
      dressing on the fifth day the skin graft has completely healed. DISCUSSION:
      Vacuum therapy is suitable for disastrous wound conditions in order to achieve a
      defect size reduction, pain reduction and create a clean wound with granulation
      tissue for further surgical defect coverage using skin grafts or flaps.

PMID- 16575639
TI  - [Optimizing vacuum therapy in extensively undermined wounds].
AB  - INTRODUCTION: Extensively undermined wound cavities represent a common surgical
      problem. By a modified vacuum therapy the healing of such wounds can be
      accelerated. MATERIALS AND METHODS: Based on our experience in selected cases
      with wound healing disorders or extremely undermined wounds following degloving
      injuries or abscess formations the application of topical negative pressure
      therapy to fix wound margins to the wound ground while at the same time allowing
      exudates emission with additional drainages is described. RESULTS: In 5 patients
      we were able to demonstrate the efficacy of vacuum dressing system described here
      with successful and lasting adaptation of the wound margins to the defect. All
      wounds were brought to permanent healing. CONCLUSION: Extensive tissue degloving
      and wound healing disorders after excessive tissue mobilization during plastic
      surgical defect coverage can be treated successfully with topical negative
      pressure therapy (TNP). Whereas longterm complete conventional polyurethane foam
      lining of wound cavities is an effective method and may be necessary in special
      situations, the application of TNP can lead to a firm adhesion of wound margins
      in extensive subcutaneous or epi-fascial wounds to the undersurface. To avoid
      exudate formation in the adjoining tissue TNP can be effectively optimized by the
      placement of drainage tubes into the surrounding tissue.

PMID- 16575640
TI  - [Optimizing delayed reconstruction of complex pressure sores by V.A.C. therapy].
AB  - V.A.C.-therapy has improved the treatment of extended pressure sores, because of
      its beneficial effect on the wound surface and the safe microbial barrier.
      Definitive reconstructive surgery can be performed earlier. Using modern aids
      fixation of the device will be possible even in difficult locations as the
      perianal area. This is important for immobile and multi-morbid patients. On the
      other hand, this area still shows limitations of the method. In recurrent cases
      it is difficult to use classical methods of reconstruction. Long-term-treatment
      is necessary, which is economically difficult. It is important for hospitals to
      cooperate with specialised wound therapeutics so that these patients can be
      dismissed earlier. This may allow reconstructive procedures, even if this takes
      several hospital stays over a long period of time.

PMID- 16575641
TI  - [Application of V.A.C.-therapy during plastic surgical treatment of a bifocal
      Marjolin ulcer].
AB  - Marjolin ulcers are scar carcinomas most often found in old instable burn scars,
      the majority histopathologically characterized as squamous cell carcinomas.
      Surgical therapy includes radical excision and subsequent defect closure. We
      report about a 69 year old patient suffering from two scar carcinomas on the
      right cheek and right chest and abdomen due to an extensive infant burn injury.
      During a 2 stage procedure, both ulcers were initially excised and resulting soft
      tissue defects were closed temporarily by applying V.A.C. therapy. During a
      second procedure defect closure on the right cheek was achieved by using a free
      radial forearm flap following neck dissection. Additionally, the extensive defect
      including chest and abdominal wall as well as the flap donor site on the left
      forearm were covered with split thickness skin grafts and subsequently secured by
      applying V.A.C. therapy for 5 days. 13 days later, the patient was discharged
      from our clinic. All skin grafted areas as well as the free flap were stably
      healed. Our report demonstrates that the application of vacuum therapy is not
      only useful during temporary closure of large wound sites but also secures
      healing of large and critical areas grafted with split thickness skin grafts in
      tumour patients.

PMID- 16575642
TI  - [Vacuum-assisted closure as temporary coverage in the "problem zone hand"].
AB  - INTRODUCTION: Vacuum therapy of hand defect problematic due to the interdigital
      folds and in particular due to the small surface. As a temporary cover in staged
      procedures, e. g. following excision of tumor-suspicious skin alterations at the
      hand, and/or at the fingers, the application of vacuum therapy results not only
      in a sterile, temporary cover of the wound, furthermore it promotes wound
      conditioning and reduction of the wound area as well as lymph and edema
      reduction. PATIENTS AND METHODS: A 75 year old female patient presented herself
      with a skin alteration at the right dorsal ring finger and the tentative
      diagnosis of a Morbus Bowen like lesion was raised. Due to the unclear
      histological status, a staged procedure with excision of the tumour and temporary
      defect coverage by means of vacuum therapy until final histological evaluation
      was indicated. We accomplished the radical excision of the unclear skin tumour at
      the proximal phalanx under preservation of the synovial sheath of the tendon.
      Subsequently, the wound was temporarily closed with vacuum therapy. Histological
      examination revealed the complete removal of a solar keratosis. Finally, after 7
      days of vacuum therapy as a sterile dressing, with obvious reduction of wound
      area and simultaneous decrease of edema, the defect was finally covered with a
      reversed cross finger flap from the adjacent middle finger. The donor site was
      covered with a full thickness skin graft harvested from the right forearm. The
      further course was without complication after flap dissection and complete
      healing. DISCUSSION: Vacuum therapy represents a usefull procedure for temporary
      wound coverage. Especially at hand defects, when nerves, tendons or bones
      following trauma or staged procedures are exposed, vacuum therapy can be
      successfully applied utilizing the special surgical "hand glove" technique.

PMID- 16575643
TI  - [Modified gloving technique for vacuum therapy in the hand].
AB  - INTRODUCTION: During the last 10 years sub-atmospheric pressure dressings
      (Topical Negative Pressure Therapy = TNP) has become a well accepted standard
      therapeutic modality in the management of acute and chronic wounds. However, in
      the hand and the fingers TNP treatment is not as an established method as
      elsewhere in the body. This is mostly due to difficulties in the technique of
      sealing wounds near the interdigital folds, especially when the interdigital
      folds are affected themselves. MATERIALS AND METHODS: Over a period of 36 months
      we treated 9 extensive open wounds of the hand with the TNP dressing procedure.
      To optimize the effective sealing procedure several methods of closure were
      applied: sterile vinyl gloves, split V.A.C. gel-straps and the "Sandwich"
      principle. RESULTS: In all cases we were able to achieve a tight vacuum sealing
      with the use of our vinyl or latex free surgical glove as an aid to cover the
      interdigital spaces. There was a rapid and complete remission of the symptoms in
      terms of edema, redness, tenderness and range of motion. The indication spectrum
      encompassed infection control, temporary coverage of exposed bone or tendons,
      intermittent irrigation with local antiseptics as well as wound preconditioning
      before skin grafting or flap coverage. For the definite closure or coverage a
      second operation was necessary in all cases. CONCLUSIONS: The TNP-dressing can be
      securely achieved even in wounds encompassing the interdigital folds or adjacent
      to the in digital spaces with a modified surgical gloving technique to aid the
      standard sealing foil. It is a suitable principle for the management of severe
      hand infections with a reduction of clinical symptoms, reduction of the frequency
      of dressing changes compared to open approaches and a significant amelioration in
      the quality of life both for patients and health care personnel.

PMID- 16575644
TI  - [Meshgraft for the final covering of chronic wounds, secured by V.A.C. therapy].

PMID- 16575645
TI  - [Changing paradigms in reconstructive surgery by vacuum therapy?].
AB  - In modern science the changes of scientific paradigm occur constantly and often
      unnoticed. Effects of new therapy procedures that are not compatible with the
      prevailing doctrines first lead to contradictory discussions and may then lead to
      new doctrines depending upon the general perception. Continuous computer-assisted
      local negative pressure therapy (vacuum assisted closure therapy/V.A.C., topical
      negative pressure treatment) has led to unexpected and impressing clinical
      results since its introduction. This has provoked a recognizable change of
      different therapeutic concepts in reconstructive surgery. Based on a selection of
      important clinical examples from reconstructive surgery following a current
      literature research the attempt is undertaken to point out recognizable changes
      of paradigms within the treatment algorithms that can be discerned after the the
      introduction of vacuum therapy in recent years.

PMID- 16575646
TI  - [Experimental principles of the V.A.C.-therapy -- pressure values in superficial
      soft tissue and the applied foam].
AB  - OBJECT OF THE STUDY: Measurement of the pressure during V.A.C.(R)-therapy in
      superficial parts of the affected soft tissue as well as at the soft tissue/foam
      interface, measurement of pressure values along bigger distances in the foam and
      the comparison of pressure transfer between polyurethane and polyvinyl-alcohol
      foams. MATERIAL AND METHODS: A multi-channel electronic transducer-tipped
      catheter system based on the piezo-resistant principle was used. Measurement was
      performed on a plain table surface, at a bovine muscle as well as in human tibial
      anterior muscle of a patient after fasciotomy. Applied pressure values by
      V.A.C.(R)-therapy-units were 50 to 200 mm Hg (continuous suction modus). RESULTS:
      100 % pressure transition through vacuum-therapy-foams to wound surface, almost
      100 % pressure transition even along 60 cm in very large polyurethane-foams using
      only one trac-pad connector. Pressure values > 125 mm Hg using polyvinyl-alcohol
      foams showed a reduction of up to 25 % in distances > 15 cm from trac-pad
      connector. On the surface of the affected soft tissue there are negative and
      positive pressure values (25 % quartile: - 25 mm Hg; 75 % quartile: + 15 mm Hg).
      DISCUSSION: Pore walls of the foam can produce positive pressure conditions
      resulting in soft tissue compression and consecutively hypoperfusion or ischemia.
      V.A.C.(R)-therapy seems to produce an heterogeneity of pressure distribution at
      the wound ground leading to pressure gradients and facilitating drainage of
      interstitial fluid. This mechanism could explain the anti-edema effects of
      V.A.C.(R)-therapy resulting indirectly in an increased nutritive perfusion.

PMID- 16575647
TI  - [Influence of V.A.C.-therapy on cytokines and growth factors in traumatic
      wounds].
AB  - OBJECTIVE: Clinical observations have shown an accelerated wound healing in
      wounds of patients treated by Vacuum Assisted Closure (V.A.C.)-therapy. The
      mechanisms of improved wound healing on cellular level have been hitherto less
      investigated. In this study the levels of proinflammatory interleukins (IL-6, IL
      8, IL-10) and growth factors (VEGF, FGF-2) in serum and wound were monitored.
      METHODS: The study included 21 patients with traumatic wounds that could not be
      closed during the first surgical intervention. The soft tissue defects (n = 21)
      were closed temporarily by Epigard. During the first second-look operation after
      2.0 +/- 0.2 days in an average, Epigard was used for another 2.5 +/- 0.4 days as
      temporary soft tissue coverage in 13 patients (group A). In the remaining 8
      patients the wound conditioning was done by V.A.C.(R) for 2.4 +/- 0.3 days (group
      B). A total of 428 samples of serum and wound fluid samples were collected during
      the first and second look operation. Levels of IL-6, IL-8, IL-10, VEGF and FGF
      were measured specific by ELISA. RESULTS: In all interleukins and growth factors
      there were significant lower serum level concentrations compared with those in
      wound fluids. During the first temporary dressing change after wound coverage
      with Epigard the wound samples showed the following levels [Mean (SEM)]: IL-6 49
      816 (19 889) pg/ml, IL-8 54 (16) ng/ml, IL-10 314 (44) pg/ml, VEGF 4 746 (766)
      pg/ml, FGF-2 494 (89) pg/ml. During the second dressing changes we monitored the
      following levels in group A: IL-6 7 218 (2 542) pg/ml, IL-8 69 (27) ng/ml, IL-10
      261 (58) pg/ml, VEGF 3 551 (661) pg/ml, FGF-2 355 (67) pg/ml. In group B the
      samples of the wound fluid showed the following results: IL-6 16 966 (4 124)
      pg/ml [p = 0.02], IL-8 223 (91) ng/ml [p = 0.03], IL-10 233 (76) pg/ml [p =
      0.38], VEGF 7 490 (1 565) pg/ml [p = 0.01], FGF-2 352 (43) pg/ml [p = 0.48].
      CONCLUSION: The increased local release of IL-6, IL-8 and VEGF in wounds after
      V.A.C.-therapy may be involved in the accumulation of neutrophil granulocytes and
      angiogenesis, which seams to play a crucial role for the accelerated granulation
      tissue formation after V.A.C.-therapy compared to wounds treated by Epigard.

PMID- 16575648
TI  - [1-year follow-up results on outpatient V.A.C.-therapy treatment -- evaluation of
      patient-data].

PMID- 16575649
TI  - [Case report of successful therapy of necrotizing fasciitis using a device of
      vacuum assisted closure].
AB  - Successful wound management is reported in a case of extended and life
      threatening necrotizing fasciitis of the leg of a poly-morbid older woman by use
      of standards of septic surgery (sufficient excision of necrotic tissue, use of
      bacteria adapted antibiotics, programmed wound revisions) and use of an
      industrial supplied device of vacuum assisted closure (V.A.C.).

PMID- 16575650
TI  - [Maggot therapy for treatment of severe infections in trauma surgery: "back to
      the future!"].
AB  - The ancient method of larval therapy for treatment of acute and chronic
      infections has become a revival and a new dimension with introduction of the
      Biobag (Vitapad). With use of this therapy trauma patients suffering infectious
      complications can be treated very effective, which can reduce the overall time
      needed for treatment and can result in diminished invalidity.

PMID- 16575651
TI  - [Clinical experience and results of using the V.A.C. instill therapy in infected
      hip- and knee prosthetics].
AB  - Since September 2005 our patients with acute endoprosthetic infection are
      treated, next to the normal wound debridement, with a full automatic vacuum drain
      system (V.A.C. instill system). This therapy unit entail a three step program.
      Based on the well known vacuum therapy, the new system contains an additional
      fluid drain and affecting period with an antibiotic or antiseptic instillation
      therapy. In the last half year we were able to treat five patients with
      endoprosthetic infection by using this therapy unit. In our opinion, we have a
      successfull method of treating patients with acute, infected big joints after
      endoprosthetic implantation. The therapy unit of V.A.C. instill is quickly
      available and easy to learn. Next to much better comfort for the patients the
      most advantage is to leave the prosthetic inside during the infection management
      with the new therapy unit. Further results in treating acute joint infections
      after endoprosthetic implantation must been shown, if this new method is to be
      the new standard in daily clinical routine.

PMID- 16575652
TI  - [The early use in traumatology of vacuum therapy for a third-degree, open forearm
      fracture with extensive decollement of the upper and lower arm].

PMID- 16575653
TI  - [Indications for use of the V.A.C.-system in the orthopedic surgery].
AB  - INTRODUCTION: The vacuum-assisted closure (V.A.C.)-therapy is accepted for an
      efficient option in the treatment of infected wounds with healing complications.
      However, reports on its use in the septic orthopedic surgery are seldom. Hence,
      the aim of this study is to demonstrate our experience with the V.A.C.-system in
      the treatment of orthopedic-related infections. PATIENTS-METHODS: Various
      musculoskeletal infections with prolonged wound healing (infections after
      Achilles tendon reconstruction, fibula osteosynthesis, dorsal spondylodesis, and
      total hip arthroplasty, skin necrosis after total knee arthroplasty and wound
      dehiscence after resection and irradiation of a liposarcoma) have been treated
      with the V.A.C.-device. After infection sanitation we performed skin graft
      transplantation in 3 cases for definitive wound closure, also assisted by the
      V.A.C.-therapy. RESULTS: An infection eradication with implant preservation,
      where necessary, could have been achieved in all cases. No complications were
      observed in the cases with the skin graft transplantations. No infection
      persistence or reinfection occurred at a mean follow-up of 36 months. DISCUSSION:
      The V.A.C.-therapy seems to be a valuable adjunct in the treatment of infected
      wounds in the orthopedic surgery, however, definitive conclusion should await the
      results of future clinical studies with large series.

PMID- 16575654
TI  - [Wound management of the deep wound infection after complex dorsoventral spinal
      column fusion L3 to S1 under application of the vacuum assisted closure].

PMID- 16575655
TI  - [V.A.C.-therapy: a treatment option for wound healing complications after
      achilles tendon reconstruction].
AB  - INTRODUCTION: The postoperative course after Achilles tendon reconstruction is
      associated with a high incidence rate of infections and wound healing
      complications, which can lead to protracted healing process and, hence, limit the
      clinical outcome. PATIENT-METHODS: A 66-year-old male was referred to our clinic
      with an Achilles tendon rupture. MRI confirmed the diagnosis, an augmented
      tenoplasty was performed for tendon reconstruction. 11 weeks after surgery the
      patient presented himself again with an open wound and local infection signs.
      RESULTS: The surgical treatment included debridement and jet lavage. The V.A.C.
      device with the white polyvinyl sponge at an initial pressure of 200 mm Hg was
      used. A pathogen organism could not be identified. For infection eradication a
      broad spectrum systemic antibiosis (cefuroxime and gentamicin) was applied. On
      3., 6. and 14. day the dressings were changed and the wound was revised under
      progredient closure. At beginning formation of granulation tissue the pressure
      was reduced to 150-100 mm Hg. At decreasing blood inflammation parameters and
      amelioration of the local wound condition the patient could check out after 3
      weeks hospitalization. After further successful ambulant management by means of
      the V.A.C.-therapy a meshgraft transplantation was performed (enlargement factor
      1.5; layer thickness 0.3 mm). The V.A.C.-device was applied again at a pressure
      of 150 mm Hg with a single dressing change after 5 days. At a follow-up of 31
      months no further complications occurred. DISCUSSION: The V.A.C.-therapy seems to
      be a valuable tool in the treatment of wounds with a critical local vascularity.
      After successful wound preconditioning the healing process of skin grafts
      transplants can be also optimised by means of the V.A.C.-device.

PMID- 16575656
TI  - [6 years V.A.C. in general surgery -- clinical data from 128 patients].
AB  - Since the introduction of vacuum assisted closure therapy (V.A.C.) at the
      Department of Surgery/St. Anna-Hospital Herne has taken place in 2000 there was a
      rapid increase of indications to use this therapy. We present data from 128
      patients who were treated with this method from 2000-2005 for different kinds of
      diseases. We report the management of a 78-year-old male patient who developed a
      Fournier's gangrene after an acute appendicitis with retroperitoneal perforation
      and an enterocutaneous fistula of the cecum. Using V.A.C. in surgery, a quick and
      safe treatment of infection and healing could be achieved.

PMID- 16575657
TI  - [Vacuum assisted closure system in treatment of small bowel fistula].

PMID- 16575658
TI  - [Vacuum-assisted fascial closure in the management of diffuse peritonitis].
AB  - The surgical treatment of patients suffering from peritonitis with an open
      abdomen is commonplace. However scheduled as well as required dressing changes
      and peritoneal lavages mean a time- and costs-intensive challenge for the nursing
      and medical personnel. Since the introduction of the abdominal dressing-kit (KCI,
      Walluf, Germany) in the management of diffuse peritonitis one expects to
      influence the patients' recovery in a positive way due to the continuous
      evacuation of intraabdominal infectious fluids, augmentation of tissue's
      granulation, prevention of fascial retraction and prevention of an abdominal
      compartment syndrome. First on trial we established 2004 in our surgical
      department the use of the abdominal dressing-kit as a routine procedure in the
      management of diffuse peritonitis.

PMID- 16575659
TI  - [Abdominal dressing -- a new standard in therapy of the open abdomen following
      secondary peritonitis?].
AB  - INTRODUCTION: The management of patients with a laparostoma due to peritonitis is
      a challenge for every surgeon and intensivist. The goal of this study was to
      compare the different treatment strategies for the open abdomen: Abdominal
      Dressing (AD), the classic V.A.C. therapy (CV) and conventional open therapy
      (CT). METHODS: Between 2001 and 2005 we identified 62 patients in 4 surgical
      departments in Austria who had to be treated with a laparostoma due to
      peritonitis. 27 patients were conventionally treated, 16 with the Classic V.A.C.
      therapy and 19 patients with V.A.C. abdominal dressing. RESULTS: The mortality
      was 3/16 (14 %) in the AD group vs. 4/12 (21 %) patients in the CV group and 18/9
      (59 %) in conventional therapy. There was no significant difference for survivors
      in the length of ICU stay: 26.6 +/- 23.0 days in the CT group, 34.6 +/- 30.2 days
      in the CV group and 38.9 +/- 27.2 days in the AD group. Apache II Score and
      Mannheimer Peritonitis Score showed no difference between the groups. CONCLUSION:
      We found a reduction of mortality in the V.A.C. Abdominal Dressing group by
      approximately 40 % (AD: 14 %, CT: 59 %). Although we could identify a difference
      in age in our retrospective study we believe that V.A.C. Abdominal Dressing is
      the important factor for the different clinical outcome. These first results
      indicate the need for further prospective evaluation of the V.A.C. Abdominal
      Dressing therapy, to prove if a new standard in the therapy of the open abdomen
      is created.

PMID- 16575660
TI  - [Role of vacuum therapy in the management of the septic abdomen].
AB  - Progress in intensive care medicine contributed substantially in lowering the
      mortality rate of patients suffering from diffuse secondary peritonitis. In the
      medical care of patients presenting a septic abdomen the persisting septic focus
      is one of the greatest problems. This is associated with other problems like
      temporary closure of the abdomen, complications due to re-laparotomies, healing
      of the abdominal wall after soft tissue infection, loss of abdominal wall
      musculature, or persisting enteral fistulas. The vacuum therapy is used with
      increasing frequency for the treatment of septic complications in different areas
      of the body. The excellent drainage characteristics of the vacuum therapy appear
      to be a therapeutic option for the control of surgically untreatable septic
      processes in the abdominal cavity. More and more experience is gathered with the
      successful treatment of enterocutaneous fistulas, small intestine and pancreatic
      fistulas as well as anastomotic leakage after rectal surgery. There exist hardly
      any evidence-based recommendations for the application of vacuum therapy for
      treatment of the septic abdomen. But the good results of temporary closure of
      open abdomen of trauma patients by the vacuum therapy arises hope that the
      results can be transferred to the treatment modalities of persisting peritonitis.
      Additionally, these patients could profit from the drainage characteristics of
      the vacuum therapy.

PMID- 16575661
TI  - [Value of V.A.C.-therapy in the treatment of sternal infections].
AB  - Osteomyelitis of the sternum is a dreaded complication after sternotomy and is
      related to high mortality. Control of infection by radical debridement is the key
      to successful treatment. Instability of the thoracic cage can lead to a high
      complication rate. 16 Patients with an infected and unstable sternum underwent
      radical debridement with resection of the sternum and adjacent ribs. 6 Patients
      (group A) received an immediate defect coverage with a pedicled muscle flap. 10
      Patients (group B) were treated with a vacuum-assisted closure (V.A.C.)-therapy
      until stabilization of their general condition and underwent defect coverage in a
      second operation. Healing of the flaps was uneventful in all cases despite minor
      problems. 5 patients of group A had severe complications with pulmonary or
      cardiac failure and thoracic instability which lead to prolonged periods of
      mechanical ventilation. 2 patients of this group died due to multi organ failure.
      All patients of group B survived and there were no major complications. All of
      the patients were free of recurrence from their osteomyelitis during follow-up.
      V.A.C.-therapy after radical resection of sternum osteomyelitis proved to be an
      effective measure to bridge time while optimizing the status of the patient and
      it's wound. With this approach we believe to have lowered the rate of major
      complications in this multi-morbid patient group by reducing the burden of one
      large operation and by improving thoracic stability.

PMID- 16575662
TI  - [The importance of vacuum therapy in the treatment of sternal osteomyelitis from
      the plastic surgeons point of view].
AB  - BACKGROUND: Since its introduction in 1997 the vacuum assisted closure therapy
      has gained widespread and is for its indications international accepted. It is
      also well established in the treatment of sternal infections a dreaded
      complication after median sternotomy in cardiac surgery. The well known positive
      effects of the vacuum therapy act as a dignified cleaning procedure between
      debridement and plastic coverage or as a temporarily closure method if the first
      debridement was properly not sufficient. METHOD AND PATIENTS: Between January
      2003 and December 2005 twenty eight patients with advanced sternal infection
      after median sternotomy were treated by radical debridement, vacuum assisted
      closure therapy and definitive plastic coverage by muscle flaps. In this article
      three patients are exemplarily introduced. RESULTS: In all patients a sufficient
      plastic coverage was achieved after radical debridement an vacuum assisted
      closure therapy. The patients received a pedicaled muscle flap. Stable wound
      condition with no signs of a recurrent sternal infection were observed in all
      patients. DISCUSSION: Vacuum assisted closure therapy acts as a link between
      radical Debridement and definitive plastic coverage in prolonged sternal
      infection after median sternotomy. Before the invention of V.A.C.(R) dressing
      changes were obliged every day in patients with deep sternal infection. The
      V.A.C.(R) therapy reduces the frequency of this painful dressing changes
      significantly and on this behalf makes life more comfortable for this mostly
      multi-morbid patients.

PMID- 16575664
TI  - [Vacuum assisted closure in the treatment of pleural empyema -- first experiences
      with intra-thoracal application].
AB  - Meanwhile vacuum-assisted closure (V.A.C.) therapy belongs to the standard
      procedures in cardiovascular surgery. Its intra-thoracal application is mentioned
      in one unique case-report in literature. We like to show our first experiences
      with this technique demonstrating three cases with pleural infection. One patient
      with bronchial stump insufficiency, one with pleural empyema and one with
      penetrating abscess of the chest was treated with V.A.C.-therapy. We applied a
      combination of microporous silicon fleece and polyurethane foam in direct
      neighbourhood to ventilated lung areas inside the thoracic cavity. One patient
      died of metastasis of his cancer disease, while wound situation and bronchial
      stump insufficiency could be treated well. Two patients could be treated
      successfully and be discharged out of the hospital. No complications due to
      V.A.C.-therapy could be seen, such as fistulas of the lung or bleeding of the
      mediastinal organs. Intra-thoracal V.A-C.-therapy can be performed as a good
      therapeutic option in the treatment of septic diseases inside the chest.

PMID- 16575663
TI  - [Vacuum assisted closure for the treatment of sternal wound infections -- rapid
      infection control and bridging to reconstructive surgery].
AB  - Vacuum Assisted Closure (V.A.C.) is a sound strategy to control severe post
      sternotomy infection. Secondary re-wiring of the sternal bone or reconstructive
      surgery may be required later to achieve complete wound closure. Ten patients
      with severe sternal bone infection underwent initial V.A.C. therapy and delayed
      surgery for wound closure. Complete wound healing was achieved in all cases. As a
      case report we describe a patient with right-sided mastectomy and irradiation for
      breast cancer, who developed severe post-sternotomy infection and sternal bone
      necrosis following CABG. A combination of V.A.C. therapy and surgical
      reconstruction using a pedicled latissimus dorsi musculocutaneous flap led to
      complete wound closure.

PMID- 16575665
TI  - [V.A.C.-treatment: a new approach to the management of septic complications in
      thoracic surgery].

PMID- 16575666
TI  - [Reconstruction of tumor induced defects in head and neck surgery with
      individualized prefabricated three dimensional flaps with the use of continuous
      vacuum therapy].
AB  - Despite recent developments in oncologic head and neck surgery extensive tissue
      and functional defects following radical tumor resections remains a surgical
      challenge. Individually prefabricated free flaps to meet the needs of the
      functional defect can be generated with the help of continuous computer-assisted
      vacuum therapy. This accelerates the pre-fabrication of three-dimensional
      composite flaps and enhances therapeutic safety. Changes of the genuine structure
      of such flaps are induced by implantation of autologous or heterologous
      transplants alone or in combination with alloplastic materials as a supportive
      element. Application of vacuum therapy is useful to accelerate the process of pre
      fabrication by the induction of angiogenesis. Besides this the continuous removal
      of wound exudate, possible seroma or haematoma and secondary compression of the
      different tissue layers improve the modelling of the three-dimensional construct.
      This article describes the technique of vacuum therapy for the pre-fabrication of
      three-dimensional pedicled or free flaps for reconstruction of defects after
      tumor resection in the head and neck area.

PMID- 16575667
TI  - [Distal extremity reconstruction for limb salvage in diabetic foot ulcers with
      pedal bypass, flap plasty and vacuum therapy].
AB  - There are numerous factors resulting in tissue damage and foot ulcers in diabetic
      patients. Critical ischaemia should be routinely excluded and an examination of
      the limb perfusion must be done in all cases with clinical suspicion of reduced
      perfusion. Pedal bypass grafting procedures in combination with flap plasty
      techniques achieve good results in patients with non-healing diabetic ulcers.
      Timing of the procedure is essential to avoid progression of gangrene. Good
      results of pedal bypass grafts support an indication at an early stage. Vacuum
      assisted wound therapy and local wound surgery can be done first to prepare
      patients with septic foot lesions for two-staged procedures.

PMID- 16575668
TI  - [Granulation tissue induced by vacuum-therapy on the exposed chondral part of the
      condyle of femur after disarticulation of the knee].

PMID- 16575669
TI  - [V.A.C. (Vacuum Assisted Closure) therapy as a treatment option in complications
      following lymphadenectomy in patients with penile cancer].
AB  - INTRODUCTION: Penile cancer is a rare tumor entity. Primary therapy consists of
      tumor excision (laser therapy, circumcision, partial or complete penectomy).
      Therapy of advanced or metastasized penile cancer is still challenging due to
      high morbidity with postoperative lymph edema, fistula, wound infection and
      resulting secondary wound healing. METHODS: In this series we retrospectively
      investigated clinical and diagnostic data from 28 patients (1995-2005) with
      penile cancer regarding their follow-up, especially in respect to morbidity after
      lymphadenectomy and the resulting therapy. We evaluated the efficacy of V.A.C.
      therapy as an alternative in this setting regarding costs and duration of
      hospital stay. RESULTS: 11/28 pats. underwent lymphadenectomy (LA) because of
      tumor stage or suspicious lymph node status. Eight of those pats. developed
      complications, as there were: lymph edema, and/or secondary wound healing with
      fistula. 4/8 pats. were treated with V.A.C. therapy. In this group a significant
      advantage regarding cost and time of hospitalization was observed. DISCUSSION:
      Despite higher primary introduction costs an early V.A.C. therapy in patients
      with secondary wound healing and lymph obstruction is advisable and resulted in a
      shortened hospitalization and reduced overall costs per patient.

PMID- 16575670
TI  - [V.A.C. instill -- first experiences on an inflammatory process of the proximal
      femur 3 years after hip-joint operation].

PMID- 16575671
TI  - [V.A.C.-instill therapy in periprosthetic infection of hip and knee
      arthroplasty].
AB  - Periprosthetic infection represents a main complication of arthroplasty. In case
      of an early infection the implant often can be left in place. Whether
      instillation of antiseptic solution using a reticulated sponge in combination
      with negative pressure wound therapy (V.A.C.-Instill) can be useful was the aim
      of our investigation. Up to now the instillation of Lavasept in combination with
      negative pressure wound therapy could be performed in three patients. In two
      cases an early infection of a hip prosthesis and one infected knee implant had to
      be treated. Following surgical debridement V.A.C.-Instill therapy was performed
      for 4-7 days followed by closure of the wound or a repeated application. Lavasept
      was used for irrigation. In all three cases retention of the primary implant
      could be achieved. The follow up now is 8 to 22 weeks. No recurrence of the
      infection occurred. After salvage of the prosthesis the joint allowed full load
      bearing and painfree mobilisation. The V.A.C.-Instill system proved to be easy to
      use. With this system early periprosthetic infection with antiseptic irrigation
      in combination with negative pressure wound therapy decreasing the bacterial
      burden, salvage of prosthesis seems to be possible. The therapy is applicable in
      hip and knee prosthesis. Final conclusions about this therapy however can be done
      only after a larger series of patients.

PMID- 16575672
TI  - [Take of mesh grafts in chronic leg ulcer patients improves by vacuum-assisted
      closure device].
AB  - Vacuum-assisted closure (V.A.C.) is an established therapeutic option in the
      management of acute and chronic granulating wounds. In recent years, little data
      has been published concerning skin graft transplantation and postoperative V.A.C.
      therapy. We report a consecutive case series of 54 patients with chronic leg
      ulcer who received a total of 74 mesh grafts. A postoperative V.A.C. therapy was
      performed in 28 mesh grafts, and 46 mesh grafts were treated with standard gauze
      therapy. In the V.A.C. group, 92.9 % grafts showed complete healing. In the
      treatment group without postoperative V.A.C. therapy, 67.4 % of the mesh grafts
      had taken. Differential analysis revealed a correlation in patients over 70 years
      of age or in patients suffering from diabetes mellitus or dermato-lipo-sclerosis.
      Particularly patients with diabetes mellitus and of greater age exhibited
      improved take rates in the V.A.C. group. The results of our study demonstrate for
      the first time the significant benefit of V.A.C. therapy after mesh-graft
      transplantation in chronic leg ulcer patients as evaluated in a clinical trial
      with a control group.

PMID- 16575673
TI  - [Multi therapy of large chronic leg ulcera: a combination of necrectomy, vacuum
      assisted closure and mesh graft].

PMID- 16575674
TI  - [Interdisciplinary management of complex chronic ulcers using vacuum assisted
      closure therapy and "buried chip skin grafts"].
AB  - HISTORY AND ADMISSION FINDINGS: We report the case of a 68-year-old female
      patient who was admitted to the hospital with deranged blood sugar levels in a
      septic condition. Due to complex chronic ulcerations of both feet she was
      intended for major amputation of both limbs. Clinical findings on admission were
      a diabetic foot syndrome with stage D IV ulcerations according to the Wagner and
      Armstrong classification, partially visible tendons and phlegmon of the lower
      leg. INVESTIGATIONS AND CLINICAL COURSE: Vascular diagnostic revealed arterial
      occlusive disease in the lower legs without chance of reconstruction.
      Enterococcus faecalis and Staphylococcus aureus were extracted in swabs from
      ulcers. After correction of metabolic status and antibiotic treatment radical
      debridement of all ulcers was carried out and vacuum assisted closure therapy
      (V.A.C.) was initiated. All wounds showed good granulation tissue after four
      cycles of V.A.C.-therapy. Interdisciplinary treatment with a plastic surgeon was
      initiated to accelerate epithelial closure. Using the "Buried Skin Chip"
      technique in combination with V.A.C.-therapy epithelialisation was completed
      within four weeks. The patient recovered well and was fully independent on
      discharge. DISCUSSION AND CONCLUSION: A goal-oriented interdisciplinary setting
      can achieve preservation of extremities even in septic patients. The combination
      of buried skin chip grafts and V.A.C.-therapy may be a feasible and promising
      procedure to achieve accelerated wound closure in those patients.

PMID- 16575675
TI  - [3-dimensional documentation of wound-healing].
AB  - The objective evaluation of the course of wound-healing represents a substantial
      parameter for the quality assurance of a modern wound management in chronic
      wounds. Established procedures exclusively based on a two-dimensional measurement
      of the wound surface with planimetry or digital photo documentation in
      combination with a metric statement of size. Thus so far an objective method is
      missing for the evaluation of the volumes of chronic wounds. By the linkage of
      digital photography, optical grid by means of digital scanner and an image
      processing software in co-operation with the company RSI we were able to do an
      accurate 3-dimensional documentation of chronic wounds (DigiSkin). The generated
      scatter-plots allow a visual, computer-assisted 3-dimensional measurement and
      documentation of chronic wounds. In comparison with available systems it is now
      possible for the first time to objectify the volume changes of a chronic wound.
      On the basis of a case report of a female patient with an venous leg ulcer, which
      has been treated with a vacuum closure therapy before and after performing a mesh
      graft transplantation, we would like to describe the advantages and the resulting
      scientific use of this new, objective wound documentation system in the clinical
      employment.

PMID- 16575676
TI  - [Patient expectations from modern wound management].

PMID- 16575677
TI  - [V.A.C.-therapy as a hygienic procedure tool: protection of the environment of
      wounds and patients with multiresistant bacteria in clinical and outpatient
      treatment].

PMID- 16575678
TI  - [Possibilities of V.A.C. therapy in outpatient surgical practices].

PMID- 16575679
TI  - [Cost-effectiveness in wound care].
AB  - INTRODUCTION: In Germany, treatment costs for pressure ulcer, diabetic foot ulcer
      and ulcus cruris sum up to Euro 5 billion p. a. (cost of materials only). The
      question is to be answered how much money could be saved to sick funds, if the
      treatment is switched from traditional wound care, e. g. hydro-colloids to Vacuum
      Assisted Closure (V.A.C.). METHODS: Clinical studies are analysed with regard to
      complication rates and speed of wound healing V.A.C. vs. traditional. Daily costs
      and the length of treatment are then correlated and compared. RESULTS: V.A.C.
      therapy significantly reduces the time for the wound closing process, hospital
      admissions and complication rates. Despite higher daily treatment costs (cost of
      material, only), the V.A.C. therapy turns out to be the superior cost-effective
      method by far. Assumed V.A.C. therapy substitutes other methods by 50 %, sick
      funds could have saved Euro 0.7 billion p. a. DISCUSSION: The V.A.C. related
      saving potential is not available to sick funds because the approval process for
      home care use is still (Jan 2006) ongoing since 1999. The improvement of the
      relevant decision making process is strongly required to faster provide better
      care and savings at the same time.

PMID- 16575680
TI  - [Cost effectiveness of V.A.C. therapy after post-sternotomy mediastinitis].
AB  - Since November 2001 all patients with postoperative sternum bone infections were
      treated with V.A.C. therapy. The mean length of stay at intensive care unit was
      reduced from 9 to 1 day and reduces costs for 33 714.- USD per patient.
      Additionally patients who had to be closed with pectoralis muscle flap had
      significant reduced length of stay at ICU (1 vs 4 days, cost effectiveness 14
      984.- USD per patient). The V.A.C. therapy after post-sternotomy mediastinitis
      significantly reduces morbidity and mortalita and is cost effective.

PMID- 16575682
TI  - Thrombotic thrombocytopenic purpura--then and now.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening
      disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and
      formation of microthrombi in several organs. The disease may manifest once in a
      lifetime or may relapse after complete recovery of the initial episode; in these
      recurrent cases, death or neurological sequelae are common final outcomes.
      Accumulation of unusually large (UL) von Willebrand factor (VWF) multimers was
      described in the plasma of patients with TTP. Such ULVWF multimers are
      synthesized in endothelial cells and megakaryocytes and are secreted into the
      blood upon stimulation. However, in healthy individuals ULVWF multimers do not
      normally circulate because they are rapidly reduced into smaller multimers soon
      after their secretion due to cleavage by a plasma metalloprotease, ADAMTS13.
      Deficiency of ADAMTS13 has been reported consistently in patients with TTP. Such
      defect may be constitutive, due to homozygous or double heterozygous mutations in
      the corresponding gene, or acquired, due to the presence of circulating
      inhibitory antibodies. It follows that in TTP patients, the absent or severely
      depressed plasma ADAMTS13 activity limits the cleavage of ULVWF multimers, which
      remain anchored to the endothelial cells in long strings. Particularly under
      conditions of high shear stress, the multimers may promote the adhesion of
      circulating platelets, initiating thrombus formation. The clinical implications
      of these findings to the diagnosis and treatment of TTP are discussed.

PMID- 16575683
TI  - Thrombotic thrombocytopenic purpura associated with von Willebrand factor
      cleaving protease (ADAMTS13) deficiency in children.
AB  - The physiopathology of thrombotic thrombocytopenic purpura (TTP) has been
      clarified since 1998, when it was shown that TTP in adults was most often
      associated with an acquired deficiency of von Willebrand factor-cleaving protease
      (ADAMTS13) due to autoantibodies, whereas TTP in children was most often
      associated with a hereditary autosomal recessive severe deficiency of ADAMTS13.
      The hereditary form of TPP (Upshaw-Schulman syndrome) is a very rare but life
      threatening disease if adequate treatment (plasma therapy) is not administered.
      First manifestations occur before age 10 in two thirds of cases and as soon as
      birth in most cases. The subsequent course is characterized by recurrent
      hemolytic and thrombocytopenic crises, with intervals between relapses from every
      3 to 4 weeks in two thirds of cases to several months or years in one third of
      cases. TTP crises are associated with cerebral vascular accidents in at least 30%
      of patients, with a risk of neurologic sequelae in approximately 20% of patients.
      Renal involvement includes frequent acute renal failure due to hemoglobinuria
      and/or thrombotic microangiopathy during hemolytic crisis and progressive renal
      deterioration in approximately 50% of cases, leading to chronic or end-stage
      renal failure in approximately 20% of patients. The clinical phenotype may vary
      from the typical congenital recurrent TTP. Some mild forms are limited to a
      fluctuating thrombocytopenia and may be misdiagnosed as idiopathic
      thrombocytopenic purpura. Phenotypic variability may be observed within a single
      family, which suggests a role of modifier genes. Fresh frozen plasma (FFP)
      replaces active ADAMTS13. Ten milliliters per kilogram FFP every 2 to 4 weeks
      suffices to maintain remission. FFP infusions are best used preventively, given
      that rescue infusions may not prevent central nervous system and renal
      involvement. It is hoped that plasmatic or recombinant purified ADAMTS13 will be
      available in the years to come.

PMID- 16575684
TI  - von Willebrand factor-cleaving protease (ADAMTS13) in the course of stem cell
      transplantation.
AB  - Transplantation-associated microangiopathy (TAM) is a severe complication of stem
      cell transplantation. Although TAM shares many features with idiopathic
      thrombotic thrombocytopenic purpura or hemolytic uremic syndrome, the prognosis
      of TAM is worse. Clinical similarities and the observation that uncleaved
      ultralarge von Willebrand factor (ULVWF) multimers are found in the circulation
      of patients suffering from TAM suggest a defect in VWF proteolysis that may be
      due to a deficiency in ADAMTS13 activity. In this study the course of 28
      consecutive patients, who received an allogeneic stem cell transplant was
      correlated to ADAMTS13 activity. Before stem cell transplantation, mean ADAMTS13
      activity was within normal range. Within the first 8 weeks, mean activity
      declined to less than half the baseline activity. Furthermore, most of the
      patients showed normalization of ADAMTS13 activity. Low levels of ADAMTS13
      activity were not correlated with clinical signs of thrombotic microangiopathy.
      However, two patients with clinical TAM had the lowest activity of all patients
      when suffering a severe bout of microangiopathy. Plasma exchange was not able to
      normalize ADAMTS13 deficiency in these patients, suggesting inactivation or
      consumption of ADAMTS13 activity in TAM.

PMID- 16575685
TI  - New aspects in the pathogenesis of enteropathic hemolytic uremic syndrome.
AB  - Shiga toxin (Stx) subtyping suggests that the clinical outcome of infections
      caused by Shiga toxin-producing ESCHERICHIA COLI (STEC) depends, in large part,
      on the STX genotype of the infecting strain. Whereas the presence of the STX2 or
      STX2C genotype is associated with the ability of STEC to cause the hemolytic
      uremic syndrome (HUS), strains possessing STX2D or STX2E have been isolated from
      patients with less severe disease. In addition to the type of Stx, the level of
      Stx production might be critical for the pathogenicity of STEC. Control of Stx
      expression appears to be at the level of transcription. Injury to microvascular
      endothelial cells is the key event underlying the pathogenesis of HUS. We could
      show that in addition to Stx, STEC also produces other putative virulence
      factors, such as cytolethal distending toxin, which can contribute to the
      endothelial injury by interference with the cell cycle, which results in
      inhibition of cell proliferation and finally cell death.

PMID- 16575686
TI  - Epidemiology, clinical presentation, and pathophysiology of atypical and
      recurrent hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) includes a heterogeneous group of hemolytic
      disorders. Among the identified causes of HUS are infections, particularly
      infections with Shiga toxin-producing ESCHERICHIA COLI (STEC), complement
      disorders, and disorders interfering with the degradation of von Willebrand
      factor (VWF). Other causes for atypical HUS include the cobalamin metabolism;
      pregnancy/hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP);
      drugs; and other disorders (e.g., systemic diseases appearing as HUS, such as
      systemic lupus erythematosus and rejection after transplantation). The group not
      related to STEC is often also called atypical HUS. Most of the occurrences of
      infectious HUS have only one episode. Recurrent episodes (recurrent HUS) have
      strong relationships to diseases of the complement system. In these two subgroups
      the prognosis is poor, with severe renal insufficiency, together with the need
      for renal replacement therapy. Severe arterial hypertension is common. Treatment
      options are limited. To better define this group of patients, the European
      Society for Pediatric Nephrology supported an initiative to develop a European
      HUS registry. In this registry, 167 patients were acquired; 73 were female
      (43.8%). The year of onset of the disease ranged from 1974 to 2005. The
      prevalence of atypical HUS/recurrent HUS can be calculated as 3.3 per million
      child population (< 18 years). Underlying disorders included factor H, factor I,
      MCP-1, pneumococci, and von Willebrand factor disturbances. In 33 patients at
      least one renal transplantation was performed (total, 55 kidneys); 18% were
      successful and 73% demonstrated recurrence or thrombosis. Treatment options were
      plasma substitution or plasmapheresis. Despite continued efforts, transplantation
      is not recommended at present for these patients. Living-related transplantation
      should be abandoned. New therapeutic strategies are urgently needed.

PMID- 16575687
TI  - Terminal complement complex (C5b-9) in children with recurrent hemolytic uremic
      syndrome.
AB  - Recurrent hemolytic uremic syndrome (recHUS) is a heterogeneous group of
      disorders. The pathogenesis of recHUS is not fully understood. recHUS has a high
      risk of development of terminal renal insufficiency and other sequelae.
      Abnormalities in complement factor H or in membrane-bound complement inhibitors
      with consecutive complement activation can be found in approximately 30 to 50% of
      the patients. Starting in 2001, we evaluated 42 patients with recHUS from five
      European countries (Germany, Austria, Hungary, Switzerland, and the Czech
      Republic). We measured the terminal complement complex (TCC) by an enzyme-linked
      immunosorbent assay using a neoepitope-specific anti-C9 antibody in 17 patients
      in plasma (native complement activation), serum (after coagulation), and zymosan
      activated serum (Z-serum; after stimulation of coagulation). We compared the
      results to those of 16 healthy persons. In patients with recHUS (eight males,
      nine females) with a median age of 10.8 years, the TCC values were higher in
      plasma (0.57 versus 0.48 microg/mL; P = 0.04) and serum (3.1 versus 2.2
      microg/mL) than in those of the control group, with a median age of 28.6 years
      (six males, 10 females) The TCC values in patients with low C3 compared with
      patients with normal C3 levels were even higher in plasma and serum, and the
      ratio was much lower. Children with recHUS have higher concentrations of TCC in
      plasma and serum. The ratio of Z-serum to serum showed significantly lower values
      in children with recHUS (96.01 versus 150.3; P = 0.01). These findings indicate a
      higher grade of complement activation and consumption in recHUS, suggesting that
      TCC may mediate cell toxicity. This may play an important role in the inferior
      outcome of these patients. The isolated substitution of factor H, or other
      complement inhibitors to block TCC formation, may represent useful therapies for
      these patients.

PMID- 16575689
TI  - The role of defective complement control in hemolytic uremic syndrome.
AB  - Atypical hemolytic uremic syndrome (HUS) is a severe disease that is
      characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute
      renal failure. Recent evidence has shown that defective complement activation and
      defective complement control is a cause of HUS. So far, mutations in single genes
      coding for the cofactor and complement regulator factor H, the membrane cofactor
      protein (MCP/CD46), the serine protease factor I, and autoantibodies to factor H
      have been linked to HUS. All of these proteins affect the same enzyme the
      alternative pathway convertase C3bBb. This article explains how alternative
      pathway activation proceeds and how defective control increases activation, which
      ultimately leads to endothelial cell damage.

PMID- 16575688
TI  - Platelet activation in hemolytic uremic syndrome.
AB  - Platelet consumption in platelet-fibrin aggregates leading to thrombocytopenia
      and small vessel obstruction are major features of the hemolytic uremic syndrome
      (HUS). Although thrombocytopenia has been correlated to poor prognosis, the
      mechanisms by which thrombocytopenia develops in HUS have not been completely
      elucidated. However, plausible explanations have been platelet contact with
      thrombogenic surfaces and/or direct contact with an aggregating agent. This
      article summarizes several mechanisms of platelet activation, interactions with
      leukocytes, chemokine release, complement activation, and antimicrobial defense.
      Specific mechanisms are outlined by which platelets may be activated, leading to
      thrombocytopenia during HUS. In diarrhea-associated HUS Shiga toxin has been
      shown to injure the endothelium, thus exposing the subendothelium, releasing
      tissue factor, and rendering the vessel wall prothrombotic. Shiga toxin also
      binds to and activates platelets. The toxin may activate endothelial cells and
      platelets simultaneously. In atypical HUS the alternative complement pathway is
      activated because of mutations in complement regulatory proteins. Mutated factor
      H does not bind to endothelium and platelets efficiently, enabling complement
      activation on these cells. In thrombotic thrombocytopenic purpura, intravascular
      platelet clotting occurs due to dysfunction of the von Willebrand factor (VWF) 
      cleaving protease ADAMTS13. Thrombi are formed by binding of platelets to
      ultralarge VWF multimers.

PMID- 16575690
TI  - Membrane cofactor protein and factor I: mutations and transplantation.
AB  - Mutations in the genes for three complement regulators-complement factor H (CFH),
      membrane cofactor protein (MCP), and factor I (IF)-have now been described in
      patients with atypical HUS. The functional effects of these mutations have been
      studied in detail and have been shown to affect secretion, expression, and
      regulatory function. Genotype-phenotype correlations have shown that the majority
      of patients with CFH, MCP, and FI mutations develop end-stage renal failure. The
      outcome of transplantation is poor in patients known to have either a CFH or FI
      mutation, with approximately 80% of patients losing the graft to recurrent
      disease within 2 years. In contrast, patients known to have only an MCP mutation
      have a satisfactory transplantation outcome. This is expected because MCP is a
      transmembrane regulator and allografts will therefore be protected by wild-type
      MCP. Combined liver/kidney transplantation for patients known to have a CFH
      mutation has not been successful to date. There is optimism that in the future,
      targeted complement inhibitors will be of major therapeutic benefit in this
      condition.

PMID- 16575691
TI  - A user's guide to the interactive Web database of factor H-associated hemolytic
      uremic syndrome.
AB  - Atypical hemolytic uremic syndrome (aHUS) mutations have been reported in the
      complement regulatory proteins factor H, factor I, and membrane cofactor protein
      (MCP). Mutations within factor H are also associated with membranoproliferative
      glomerulonephritis and age-related macular degeneration. The increasing amount of
      information on aHUS requires organization if it is to be usable. Accordingly, an
      interactive factor H aHUS Web database has been developed (http://www.fh-hus.org)
      that integrates genotypic, phenotypic, and structural information for mutations
      within human factor H. This provides a valuable tool for the interpretation of
      previously reported aHUS mutations, and provides prediction and analysis tools
      for new mutations. It will be extended to include mutations in factor I and MCP.
      Here, we describe how to use this Web database as a research tool, and indicate
      possible future directions depending on feedback from the clinical community.

PMID- 16575692
TI  - [Sociodemographic differences in the participation in "early detection of cancer
      examinations" in Germany--a review].
AB  - In 1971 a statutory programme aiming at the early detection of cancer was
      established in Germany. Since then, acceptance has been low, especially among
      men. In 2002, 49 % of the women, but only 20 % of the men entitled to screening,
      took part in the free preventive medical screening. This paper gives an overview
      of the research done in Germany between 1973 and 2003, examining the associations
      of sociodemographic factors with participation in cancer screening. All studies
      show that participation rates increase steadily with age in men, but decrease in
      elderly women (55 years and older). Participation rates among women are
      significantly associated with educational level and occupational status. Among
      men, however, the relationship between socio-economic status and attendance
      appears to be less pronounced. Since 1971, participation rates have increased
      much more among women than among men, but, interestingly, the reasons for the
      gender differences in attendance rates have not been studied until now. Variables
      which were identified in international studies as predictors of participation,
      such as physician's recommendation or marital status, should be acknowledged in
      future research.

PMID- 16575693
TI  - [Treatment results from inpatient psychosomatic rehabilitation of Turkish
      migrants: a prospective study].
AB  - Psychosomatic rehabilitation and the concluding social-medical assessment
      constitute a particular challenge. The aim of this study was to examine whether
      inpatient psychosomatic rehabilitation in the context of an integrated treatment
      concept, conducted in Turkish and German, is effective in the rehabilitation of
      Turkish migrant laborers, and what concluding socio-medical assessment results
      from this treatment. 195 Turkish patients--44 male and 151 female--received
      inpatient psychosomatic treatment for approximately 40 days. Sociodemographic,
      psychiatric and social-medical data were recorded, as well as Symptom Checklist
      (SCL-90-R) testing upon admission and discharge. A predominant number of patients
      were laborers, with a low level of primary education, who were afflicted with
      psychosocial problems and dissatisfaction with their workplace and who first came
      into psychosomatic treatment many years following the onset of their illness.
      Many of them had a clearly defined desire to retire. At the end of their
      admission, a significant improvement in almost all the scales of the SCL-R-90 was
      ascertained on the one hand, but on the other, adequate socio-medical results
      were hardly observed. The symptoms' improvement would confirm that the
      combination of service offerings in Turkish and German proved themselves. A
      portion of the patients (approx. 40 %) were classified subsequent to treatment as
      capable of working for 6 hours or more. Nevertheless, approximately approx. 75 %
      still sought to retire. Timely psychosomatic treatment could counteract
      chronification of the illness and the establishment of a steadfast desire to
      enter retirement, and consequently represent an improvement in the prognosis.
      Likewise, consistent psychosomatic training of physicians, as well as systematic
      prophylactic measures with the migrant laborers, should be considered.

PMID- 16575694
TI  - [Quality management in sociopsychiatric service: the use of routine data in
      efficiency control and care planning].
AB  - Caring for psychiatric patients, Social Psychiatric Services (SpDi) carry out
      advising and therapeutic tasks and give medical opinions. They also participate
      in the management of the community psychiatric care system. The services differ
      widely in giving priorities to these tasks. In Germany there are no standards
      concerning quality and quantity of individual help being offered by SpDis.
      Evaluation of this individual client related help is essential for quality
      management. Besides rates, which partly describe the utilisation of the service,
      such parameters are of interest that hint at the psycho-social risk. Furthermore,
      figures indicating continuity or discontinuity of help are of importance. The
      statistics of the documentation in 1999 and 2000 of the SpDi Wolfsburg serve as
      an example for such an evaluation.

PMID- 16575695
TI  - [Incidence of hip fracture in Germany--person-related analysis of health
      insurance population].
AB  - BACKGROUND AND PURPOSE: An increasing number of hip fractures were reported world
      wide during the last decades. Up to now incidence data are rare for Germany. The
      aim of this study is to determine actual person-related age- and sex-specific
      rates of hip fractures in Germany. METHODS: The linkable and person-specific but
      non-identifying database of a German statutory health insurance company, Gmuender
      ErsatzKasse (GEK), was used. All subjects who were admitted to hospital with a
      primary diagnosis of hip fracture (ICD-10: S72.0-S72.2) in 2004 were identified.
      Incidence rate ratios (IRR), age- and sex-specific rates (per 1000 person-years)
      were calculated. Annual numbers of hip fractures for all persons covered by
      statutory health insurances (Gesetzliche Krankenversicherung- GKV) and the German
      population were estimated. RESULTS: The incidence of hip fracture increases
      exponentially with age. Hip fractures occur 129 times more often (IRR: 129.07; 95
      % CI: 66.55 - 269.78) in women aged 90 - 94 years and 79 times more often (IRR:
      78.97; 95 % CI: 30.02 - 185.87) in men aged 90 - 94 years compared to those aged
      50 - 54 years. Approximately 101 037 (95 % CI: 91 779 - 110 294) persons are
      annually admitted to hospital in Germany due to this event. CONCLUSION: Hip
      fractures are common in the elderly and especially in women. Because of
      demographic changes and a possible secular trend an increasing number of hip
      fractures are to be expected in the future.

PMID- 16575696
TI  - [BeKi--an initiative for nutrition education in children: program description and
      evaluation].
AB  - OBJECTIVES: The State Initiative Be KI is carried out statewide by the Baden
      Wurttemberg Ministry for Nutrition/Food and Rural Area since 1980. Be KI
      addresses all target groups involved in the upbringing and education of children
      from age 6 months up to the end of the 6th grade and provides factual, validated,
      and independent information on child nutrition and nutrition education. Recently
      a comprehensive evaluation was carried out to assess the public health impact.
      Program, design and results of the evaluation are presented. METHODS: According
      to the RE-AIM Model for health promotion programs the evaluation assesses the
      public health impact in regard of individual and institutional reach, efficacy,
      adoption, implementation, and maintenance by various methods (e. g. written
      surveys and interviews with experts of child nutrition, in day care facilities
      and primary schools supplemented by internal data of the Ministry). RESULTS: Be
      KI represents the nutrition education program for children in the German language
      area with the longest uninterrupted operation span. The number of assignments of
      the child nutrition experts has been increasing ever since Be KI's official
      inception in 1980. During the school year 2004/2005 the experts carried out 6090
      assignments, predominantly in primary schools which accounted for 60% of the
      assignments. About a third of schools know Be KI. The majority of kindergarten
      and school teachers who know the experts of child nutrition or the compilation
      use these offers. Many teachers use Be KI-components without knowing that they
      belong to Be KI. As a result of Be KI some of the teachers noticed short-time
      changes: pupils eat healthier break-time snacks and change their attitude towards
      a more balanced diet. Concerning the frequency of nutrition education and
      teachers attitude there are hardly any differences between institutions with Be
      KI and without Be KI. CONCLUSION: Be KI meets the main requirements of effective
      nutrition education programs for children: it is creative, engaging, inexpensive
      an widely dissiminated. Contents and methods of the provided materials correspond
      to the development level of the target groups. But communication and networking
      with educational institutions as well as public relations should be intensified
      and teachers in day care facilities and school teachers should be motivated to
      work with the Be KI-materials on their own (empowerment). Room for improvement
      exists in regard of a permanent straightforward evaluation system and a more
      pronounced orientation of the prevention program towards the social environment
      would be helpful.

PMID- 16575697
TI  - [Why woman postpartum resume smoking].
AB  - BACKGROUND: Following a successful period of nicotine abstinence during pregnancy
      approximately 50% of all women relapse to smoking during the 6 months after
      delivery. About 34% of all children are exposed to environmental tobacco smoke
      due to maternal smoking. The objectives of this study are: (a) which women
      postpartum intend to start smoking again, (b) how does the intention to resume
      smoking influence the smoking status after 6 months and (c) what are the
      individual reasons to start smoking again. METHOD: Four weeks after giving birth
      (T0) sociodemographic variables, smoking behaviour before pregnancy and the
      intention to resume smoking were assessed in a sample of 301 women who stopped
      smoking before or during pregnancy. Six months after giving birth (T1) 285 women
      answered questions regarding their smoking behaviour and reasons for relapse.
      RESULTS: After giving birth 13% of the women intended to start smoking again.
      There was no statistical difference between women intending to start and women
      not intending to start smoking again with regard to sociodemography and smoking
      behaviour (p > 0.05). Six months later of these significantly more women smoked
      compared to the women without intention to resume smoking (68% vs. 27%, chi2 =
      23.6; df = 1, p < 0.05, OR = 5.5). Individual reasons to resume smoking were
      reported by 50 % of the women, stress being the most frequent reason. DISCUSSION:
      At least one of ten women who were abstinent during the course of their pregnancy
      intends to start smoking again. They do not differ from women not intending to
      resume smoking. The intention to resume smoking has a predictive value for an
      early relapse, but also every fourth woman without intention resumes smoking.
      Just half of the women report a personal reason for relapsing. The results
      underline the need for proactive interventions for relapse prevention.

PMID- 16575698
TI  - [Alumni of medical sciences and their life satisfaction].
AB  - OBJECTIVES AND METHODS: Medical doctors are especially burdened with
      psychological and social aspects of their occupation. These circumstances may
      lead to low life satisfaction and substance abusing behaviour and burn out
      symptoms are probable. In this paper we investigate, if alumni of medical
      sciences show lower life satisfaction compared to their peers. If so, we want to
      know, which factors influence this result. This survey is based on n = 671 alumni
      of medicine in seven German universities. RESULTS: The life satisfaction of
      alumni differs significantly from the peer sample. Outstanding are the highly
      significant and powerful differences to the scale "leisure". It was evident by an
      iterative regression that the variables "extreme input at work",
      "instrumentality/masculinity", "effort-reward imbalance",
      "expressivity/femininity" as well as "career self-efficacy-expectation", clarify
      43 % of the variance in the group of alumni working by the time of enquiry.
      CONCLUSIONS: The results point out, that already alumni of medical science are in
      the "circle of burn-out". Their life satisfaction is more affected, if the
      workload is perceived high and the perceived benefits are low. Individual as well
      as external aspects influence life satisfaction and can be a starting-point for
      prevention.

PMID- 16575700
TI  - Aesthetic facial surgery of male patients: demographics and market trends.
AB  - Evaluation of member survey data from the American Academy of Facial Plastic and
      Reconstructive Surgery (AAFPRS) and the American Society for Aesthetic Plastic
      Surgery (ASAPS) from 2000 through 2004 reveals several procedure-specific as well
      as overall trends regarding utilization of aesthetic facial enhancement services.
      This gender-specific 5-year retrospective review indicates that males undergo
      significantly fewer procedures than females except for surgical hair restoration
      and otoplasty. There is a slight general trend toward decreased surgical but
      increased nonsurgical facial enhancement procedures. On a case per physician
      basis, AAFPRS physicians performed significantly more procedures for both males
      and females for every procedure and every year evaluated. Evaluation of age group
      data indicates that the 40- to 59-year-old age group accounts for the majority of
      surgical and non surgical facial enhancement requests. Despite anticipated growth
      of the 60- to 79-year-old age group, the 40- to 59-year-old age group is
      projected to remain relatively stable. Although continuing to pursue aesthetic
      facial enhancement services in significant numbers, men still represent a vast
      untapped market. This study yields important demographic and trend information
      that has implications for the current and future delivery of aesthetic facial
      enhancement services.

PMID- 16575701
TI  - Special considerations for the male patient: things I wish I knew when I started
      practice.
AB  - This article is an introduction to dealing with the male patient in a facial
      plastic surgery practice. It combines experience, data from other sources, and
      personal opinions to assist especially the younger surgeon. Topics include trends
      involving males in society and in facial plastic surgery, physical and mental
      considerations, types of procedures, and types of personalities. It carries this
      subject forward to explore briefly more difficult personalities and unhealthy
      types of patients as well as a few possible scenarios that the surgeon might
      encounter.

PMID- 16575702
TI  - Rhinoplasty in male patients.
AB  - The complexities of rhinoplasty are further emphasized when this operation is
      undertaken in the male patient, and a growing percentage of the rhinoplasty
      population comprises men. We review the senior author's approach to rhinoplasty
      analysis, preoperative consultation, and surgical techniques that have been
      successfully employed for over 40 years. Specific recommendations and
      modifications to these techniques are discussed as they relate to the rhinoplasty
      operation in male patients.

PMID- 16575703
TI  - Male revision rhinoplasty: pearls and surgical techniques.
AB  - Male revision rhinoplasty surgery is the most difficult and challenging procedure
      that facial plastic surgeons perform because males usually have thick nasal skin,
      which is more difficult to re-support and project the nasal tip, and often have
      high or unrealistic expectations. The primary etiology for the need for male
      revision rhinoplasty is a primary rhinoplasty with aggressive lower lateral
      cartilage reduction that causes tip ptosis and loss of projection. The goal to an
      aesthetically pleasing revision rhinoplasty is to re-create adequate tip
      projection and an intact strong tripod complex. Following tip reconstruction, the
      height and width of the dorsum should be set. For male revision nasal surgery, a
      clear and thorough knowledge of nasal anatomy, function, and surgical techniques
      is paramount. Having an extensive preoperative discussion including expectations,
      outcomes, and a detailed list of potential complications with the patient can
      prevent physician-patient mis-communication. Prior to surgery, review the
      examination, previous operative summary, photographs, nasal analysis sheet,
      problem list, and plan and then proceed with the surgical treatment.

PMID- 16575704
TI  - Rejuvenation of the forehead and eyelid complex.
AB  - The goal of this article is to explain both the options and the techniques that
      are available when considering the rejuvenation of the eyelid and brow complex.
      We first explain the relevant anatomy. We then list and explain the different
      techniques with both the brow lift and the blepharoplasty. During this discussion
      we also explain a newer technique that we have been using. This combines the
      endoscopic technique with a trichophytic incision. The selection of patients is
      discussed in reference to which technique is appropriate given each patient's
      particular anatomy and desired effects. We also highlight the unique differences
      that the male patient presents.

PMID- 16575705
TI  - Rejuvenation of the lower eyelid complex.
AB  - Blepharoplasty is one of the most common cosmetic surgeries performed on the male
      patient. Whereas in the past the male patient would present later in life for
      eyelid surgery to address functional issues, he now presents earlier in life with
      an interest in aesthetic improvement as the primary motivating factor. This
      article reviews the approach of the senior author (SWP) to rejuvenation of the
      lower eyelid complex. Specifically, we discuss the indications for and techniques
      of the transcutaneous and transconjunctival approaches for blepharoplasty. As
      well, adjunctive procedures for rejuvenation of the lower eyelid complex,
      including fat transposition, lateral canthoplasty, and skin resurfacing, are
      reviewed.

PMID- 16575706
TI  - Subperiosteal deep plane rhytidectomy: the composite midface lift.
AB  - Techniques for facial rejuvenation have long involved specific remedies for each
      facial segment affected by the aging process. Traditional facial rejuvenation
      techniques have addressed the anterior neck and platysma complex as well as the
      acquired jaw deformity. These techniques often left the nasolabial complex and
      the "infraorbital hollow" un-addressed. Modern techniques, including the
      composite rhytidectomy, the subperiosteal midface lift, and the deep-plane and
      the triplane rhytidectomy, have contributed to redefining the challenge of
      correcting the problem of the orbicularis-malar soft tissue complex descent and
      as such focus on a particular segment of the facial rejuvenation. This evolution
      of the facelift demonstrates that one size does not fit all and that surgeons
      should consider their rejuvenations to be not a generic facelift but a midface,
      lower face, and neck lift. This concept has evolved into our appreciation of
      distinct surgical zones. This is especially important in males, and adjunctive
      techniques such as the ones we describe may add benefit and enhance the final
      result in male patients. As discussed, the male anatomy, because of its increased
      surface area and weight, is more difficult to gain leverage with in rejuvenation
      procedures. The author describes his preferred technique for facial rejuvenation
      in males, the subperiosteal deep plane rhytidectomy (SPDPR), which combines a
      deep plane rhytidectomy with a subperiosteal dissection. Although combining
      subperiosteal "release" of midfacial anatomy has been reviewed by other authors,
      the combination of subperiosteal release and deep-plane rhytidectomy has not been
      previously reported or advocated. The operative technique, complications, and
      results of this combined technique are reviewed. The procedure as described is
      used as an isolated procedure for midfacial descent as well as an incorporated
      technique when completing a "full" rhytidectomy.

PMID- 16575707
TI  - Purse-string platysmaplasty: the third dimension for neck contouring.
AB  - Techniques and concepts for treatment of the aging neck have been evolving since
      the late 1960s and rely on two-dimensional anterior approximation with lateral
      imbrication of the platysma with or without submental fat reduction, However, the
      medial approximation can sometimes give a "boxy" appearance to the anterior neck,
      especially if anterior shifting of the platysma recurs after platysmaplasty with
      laxity redeveloping in this midline location. The "purse-string" platysmaplasty
      (PSP) is a new concept in neck contouring that facilitates an enhanced definition
      for the cervicomandibular transition to better simulate the well-defined contour
      of this transition that is present in youth. It aids in the contouring of
      difficult poorly defined necks and in male patients. The PSP adds a "third
      dimension" to neck recontouring by invaginating the platysma with a plication
      suture and pexing the platysma, without incising it, to deeper neck fascia with a
      technique that adds support and definition to the neck contour. The PSP can be
      performed in patients undergoing a full rhytidectomy as well as in individuals
      having isolated neck rejuvenation. The PSP is especially helpful in rejuvenating
      the male lower face and neck because of the relatively heavier deeper structures
      of the male neck and the need to enhance definition along the jawline.

PMID- 16575708
TI  - Laser facial plastic surgery for men.
AB  - The demand for laser facial plastic surgery for men has been increasing. Because
      men tend not to wear make-up and do not wish to take the time off from work
      associated with surgical procedures, they prefer laser type procedures that
      usually have minimal associated recovery. These procedures can be used to treat
      multiple conditions including: photoaging, acne, acne scars, superficial
      cutaneous problems, and rhinophyma.

PMID- 16575709
TI  - Otoplasty.
AB  - Multiple techniques have been advocated over the years for the appropriate and
      natural-appearing correction of the prominent ear. There is no single technique
      that can re-create the complex three-dimensional nature of the otherwise normal
      human ear. We have to evaluate each individual ear and patient and correct the
      abnormalities with a technique that each surgeon feels comfortable with and that
      can repeatedly provide gratifying results. Ultimately, the simplest technique
      that can obtain the maximum effect should be employed. A concentration on the
      male patient and specific concerns with these patients are discussed. Multiple
      techniques are presented to adequately treat a variety of anatomic variations.
      Surgical complications and their treatment are also discussed.

PMID- 16575710
TI  - Aesthetic facial surgery for the asian male.
AB  - Cosmetic surgery of the Asian face has become increasingly popular in the Far
      East and the West. The Asian male identity has undergone an evolution in Western
      media toward a more positive change. The standards of beauty have also changed,
      being defined by more multicultural models and styles of dress than before. To
      undertake cosmetic surgery of the Asian face, particularly of the Asian male,
      requires a different psychological understanding of the individual as well as an
      entirely different surgical technique in most cases. This brief article does not
      delve into the technical details of each procedure but concentrates on the
      salient differences in how to approach the Asian male patient for each of the
      different procedures, including Asian blepharoplasty, augmentation rhinoplasty,
      lip reduction, dimple fabrication, otoplasty, facial contouring and aging face
      procedures, and hair restoration.

PMID- 16575711
TI  - Emerging trends and techniques in male aesthetic surgery.
AB  - Cosmetic surgery has witnessed explosive growth over the past few years, and with
      this has come growth in male aesthetic surgery. Increases have been seen in the
      number of nonsurgical as well as surgical treatments. Rhinoplasty, hair
      transplantation, and blepharoplasty continue to be the most common surgical
      procedures. New trends include rapid growth in nonsurgical treatments, especially
      Botox Cosmetic and microdermabrasion. New fillers have expanded the options for
      men, including long-lasting Restylane and Radiesse. Sculptra offers a new option
      for correction of human immunodeficiency virus-associated lipoatrophy. Fractional
      photothermolysis and Thermage offer new options in resurfacing.

PMID- 16575712
TI  - [Comparison of three outpatient therapy forms for treatment of chronic low back
      pain-- findings of a multicentre, cluster randomized study].
AB  - The AOK Baden-Wurttemberg health insurance fund initiated a study on the
      outpatient rehabilitation of patients with chronic low back pain, aimed at
      improving the treatment concept for its insurees with chronic low back pain
      (START). This model project was scientifically guided by the Hochrhein-Institute
      in Bad Sackingen. The paper compares the effectiveness of Enhanced Outpatient
      Physiotherapy (Erweiterte Ambulante Physiotherapie, EAP), Outpatient
      Rehabilitation (Ambulante Rehabilitation, AR) and Medical Training Therapy
      (Medizinische Trainingstherapie, MTT) in patients with low back pain. In seven
      regions in Baden-Wurttemberg, one of these three intervention forms was provided
      to the patients. A total of 1,274 patients were included in the study. The AOK
      Baden-Wurttemberg patients receiving treatment in one of the three intervention
      forms were seriously restricted in both the physical dimension of their health
      status and in their physical mobility in everyday life and at the workplace.
      Besides, they frequently reported considerable psychosocial strain. The three
      interventions led to significant and relevant decreases in pain intensity and to
      an improved health-related quality of life. There were no significant differences
      between the various treatments in terms of effectiveness. The patients shared an
      equally high satisfaction with the treatment received. In MTT, the total therapy
      length of 15 weeks was by far longer than in AR and EAP (about 5 and 8 weeks).
      Unlike AR and, in parts, EAP, patients may continue to work while participating
      in MTT. Therefore an immediate therapy start within a week was more likely
      possible in MTT (59 %) than in AR (10 %) or EAP (23 %). In evaluating the results
      a number of restrictions have to be considered. Nevertheless, based on our
      research findings, the following can be concluded: MTT is a suitable therapy
      concept in patients with low back pain characterized by a rapid start and--
      compared to the other two concepts-- by lower therapy costs. MTT might represent
      a meaningful therapy element also in new forms of provision such as integrated
      services. Patients showing severe psychosocial strain should be assigned to an
      interdisciplinary therapy as it is provided by inpatient and outpatient
      rehabilitation facilities. For effective differential assignment to the various
      programmes, realization of a standardized rehab assessment is an important
      precondition.

PMID- 16575713
TI  - [Evaluation of the Extra Short Musculoskeletal Function Assessment questionnaire
      XSMFA-D in patients with musculoskeletal disorders and surgical or medical in
      patient treatment].
AB  - AIM: The present study had the objective of evaluating the psychometric
      characteristics of the shortened 16-item version of the German Short
      Musculoskeletal Function Assessment questionnaire (XSMFA-D), which was designed
      for routine assessment of functional capacity in patients with various
      orthopaedic disorders treated either surgically or medically. METHODS: A total of
      382 patients from seven different samples with either osteoarthritis of the knee,
      osteoarthritis of the hip, rheumatoid arthritis or rotator cuff tear treated
      either in surgical hospitals or rehabilitation settings were assessed both before
      and after treatment. The XSMFA-D was compared with both questionnaires measuring
      similar constructs and widely accepted indicators of health status in
      musculoskeletal disorders. Psychometric characteristics were computed. RESULTS:
      The internal consistency (Cronbach's alpha) exceeded 0.90 in most cases for the
      function index and was between 0.80 and 0.90 in most cases for the bother index
      of the XSMFA-D. Retest-reliability was between 0.80 and 0.95 for the function
      index and between 0.60 and 0.92 for the bother index. Correlations between the
      XSMFA-D subscales and the other questionnaires were substantial, showing
      construct validity. Criterion validity was also demonstrated as significant
      relationships with accepted external parameters such as function tests,
      judgements by physicians, pain self-ratings by patients and disease severity
      scores were found. Sensitivity to change was as high as for the other assessment
      instruments used in this study. CONCLUSIONS: The XSMFA-D, a very short assessment
      instrument, proved to be practical, reliable, valid and sensitive to change among
      the various patient samples studied. It may be recommended for the assessment of
      patients' state as well as the evaluation of treatments.

PMID- 16575714
TI  - [Improvement of anxiety and depression in women with breast cancer during
      inpatient oncological rehabilitation-- results of a prospective study].
AB  - PURPOSE: Investigation of the influence of an oncological inpatient
      rehabilitation programme on anxiety and depression in women with breast cancer.
      PATIENTS AND METHOD: 198 women with breast cancer, aged 25 to 75 years, filled in
      the Hospital Anxiety and Depression Scale (HADS) German version at the beginning
      and end of inpatient rehabilitation. Focus was set on the frequency of anxiety
      and depression. Therefore proportions with 95 % confidence intervals (CI) were
      built. The before-after comparison of HADS-scores was made using the signed rank
      test with two-sided level of significance of alpha = 5 %. In addition effect
      sizes were calculated. Possible relations between the scores at the beginning of
      rehabilitation and the patients' age or the interval since diagnosis were
      analysed by calculating correlation coefficients. RESULTS: At the beginning of
      rehabilitation a state of anxiety was probable in 23.2 % (CI [17.3 %; 29.1 %] of
      the women and one of depression in 9.1 % (CI [5.8 %; 13.9 %]). In other words,
      they reached a level of >or= 11 score points on each scale. No correlation was
      found with the age of the patients or the time interval since diagnosis (|r| <or=
      0.192). At the end of rehabilitation 67.5 % (CI [61.0 %; 74.0 %]) and 60.9 % (CI
      [54.1 %; 67.7 %]), respectively, of the women showed an improvement of anxiety
      and depression. The before-after difference was a median + 2 points (anxiety) and
      + 1 point (depression), resp., with a positive value representing an improvement.
      The changes after rehabilitation were statistically significant with p < 0.0001.
      The effect sizes ranged from 0.37 to 0.50. CONCLUSIONS: After the end of primary
      therapy, women with breast cancer frequently suffer from anxiety or depressive
      disorders, with no correlation to the patients' age or time since diagnosis. By
      an inpatient oncological rehabilitation programme both anxiety and depression can
      be improved very successfully. Whether these results represent a long-term effect
      is currently being evaluated in a randomised prospective study.

PMID- 16575715
TI  - [Development of cardiovascular risk factors in patients after coronary artery
      bypass grafting with an in-hospital rehabilitation programme (WHO Stage I of
      Rehabilitation): 1-year follow-up].
AB  - BACKGROUND: The purpose of this study was to evaluate the influence of an in
      hospital (stage I of rehabilitation) individualized motivation programme for life
      style change on the cardiovascular risk factors of patients after coronary artery
      bypass grafting (CABG). METHODS: 142 consecutive patients undergoing CABG because
      of coronary heart disease were divided into two groups. Group I received the
      usual care; Group II received the intervention (individual motivation programme).
      Medical variables concerning all cardiovascular risk factors and the current
      medication plan were evaluated on admission and one year after surgery. RESULTS:
      After 12 months significant reductions in systolic blood pressure (p = 0.002),
      LDL-cholesterol (p = 0.023) and triglyceride (p = 0.046) were found in the
      intervention group on comparison of the two groups. The HDL cholesterol improved
      in the intervention group and decreased slightly in the control group. Both
      groups showed an improvement in diastolic blood pressure, Body Mass Index, blood
      cholesterol and blood glucose values. The intervention did not show a significant
      influence on smoking and medication habits. CONCLUSION: An individualized
      motivation programme starting in the acute hospital may positively influence
      cardiovascular risk factors with ongoing success.

PMID- 16575716
TI  - [Rehabilitation, social medical evaluation and counselling in HIV-infected
      patients].
AB  - An inpatient rehabilitation programme for HIV-infected patients is described.
      Since the early nineties some 1,200 patients with HIV infection have been treated
      in our internal and orthopaedic rehabilitation clinic. Beside internal and
      orthopaedic diagnostics, supporting compliance with antiretroviral therapy,
      motivating the patients for regular moderate exercises and specific nutritional
      counselling are major issues of the programme. From the psychological point of
      view, the patients are offered to aquire relaxation and stress coping techniques,
      to take part in non-smoking courses and to use individual psychological
      counselling in case of depression or panic. In addition, all HIV-infected
      patients are offered individual advice on their disease and necessary changes in
      lifestyle. Finally, the programme includes social medical evaluation and
      counselling. As the majority of the patients are still working or are of working
      age, evaluating the capacity for work and potential introduction of occupational
      rehabilitation measures are prominent. Almost 70 percent of the HIV-infected
      patients who had been treated in our clinic over the last few years were fully
      capable of returning to their previous occupation. Our experiences demonstrate
      that statements such as rehabilitation of AIDS patients being useless because of
      its missing prospects of success, are not up-to-date any longer. Since
      introduction of combination antiretroviral therapy many patients with HIV
      infection are able to return to their previous occupation if they receive the
      necessary medical und psychosocial support.

PMID- 16575717
TI  - [Relationship between self-efficacy expectations and socio-medical status of
      patients with persistent somatoform pain disorder (ICD-10: F45.4)].
AB  - OBJECTIVE: The object of this study was to investigate the connection between
      self-efficacy and socio-medical status as well as the connection between changes
      in both areas in patients with somatoform pain disorder. METHOD: In the framework
      of a naturalistic design, a total of n = 316 patients with somatoform pain
      disorder were investigated at the beginning and end of psychosomatic in-patient
      rehabilitation regarding self-efficacy (Aachener Selbstwirksamkeitsfragebogen -
      ASF) and socio-medical status (application for pension, subjective need for
      pension, periods of sick leave, pain chronicity). The data were analysed by
      linear structural equation models in confirmatory factor analyses with cross
      validation. RESULTS: The postulated model for correlation between self-efficacy
      and socio-medical status at the beginning of the in-patient treatment could be
      confirmed and showed a significant correlation coefficient between both areas.
      The postulated model for correlation between changes in self-efficacy and socio
      medical status from beginning to end of the in-patient treatment could also be
      confirmed and showed a high correlation coefficient between both areas.
      CONCLUSIONS: In patients with somatoform pain disorder self-efficacy showed a
      significant correlation with the socio-medical status. Moreover, high
      correlations were found between changes in both areas. The increase of self
      efficacy should therefore be a major goal in all therapies.

PMID- 16575718
TI  - [Validity of patient self report data in rehabilitation research: identifying
      circumstances of the patients' completion of questionnaires].
AB  - BACKGROUND: Self-report questionnaires have become wide-spread and are an
      integral part in different fields of rehabilitation. However, it is still unclear
      to what extent the validity of the patients' reports is affected by motivational
      factors. How difficult is it for the patient to fill out questionnaires? What are
      the situational characteristics in which the patients fill them out? The present
      study aims to identify the situational, motivational and cognitive requisites of
      the respondents and to analyse possible impacts on the validity of self-reports.
      METHOD: A total of n = 105 patients scheduled for inpatient rehabilitation were
      interviewed by means of a guided open-ended interview in the admission phase. It
      is a consecutive sample of all admissions in two rehabilitation clinics in
      Schleswig-Holstein, which provide each patient with a questionnaire to fill out
      prior to their stay. The analysis involved a description of statements
      (categories) that have been derived by content analysis based on the patient
      interviews. In addition, physicians rated various patients' characteristics at
      the end of their hospital stay. RESULTS: The participation rate of the patients
      was 95.5 %. Of all patients, 95 % filled out the questionnaires at home, 69 %
      without a break. 57 % of the patients interviewed had filled out the
      questionnaires by themselves without any help, another 22 % worked it through
      together with their partner or spouse. The extent of influence on the responses
      appeared to be dependent on the amount of help necessary. In a substantial number
      of patients the questionnaires were regarded as an "official" document that had
      to be worked through meticulously. Physicians attested 96 % of the patients to
      have provided honest reports with regard to personal characteristics, and 95 % to
      have shown a sufficient degree of willingness of self-disclosure. By and large
      the patients' perceptions of themselves fit with the perceptions the physician in
      76 % of the patients from the physicians' point of view. All patients except one
      were attested a positive motivation to take part in rehabilitation activities in
      the clinic by the physician. In individual cases there were substantial deficits
      of cognitive capacities necessary to work through a questionnaire, as well as
      limitations in literacy. Four patients had insufficient mastery of the German
      language. DISCUSSION AND CONCLUSION: The vast majority of the patients possessed
      sufficient motivational and cognitive prerequisites to provide valid self
      reports. Patients with problems in responding asked partners or others for help,
      its impact on the self-reports being as yet not clear-cut. In individual cases it
      can not be ruled out that patients who think about early retirement provide
      distorted statements.

PMID- 16575719
TI  - The bacteriologic yield in children with intrathoracic tuberculosis.
AB  - This report documents the bacteriologic yield in children who received treatment
      for intrathoracic tuberculosis in an area where it is highly endemic. A total of
      307 children were included in the study, and bacteriologic confirmation was
      achieved in 122 (62.2%) of 196 children from whom specimens were collected. The
      lowest bacteriologic yield was recorded for the 69 children with uncomplicated
      lymph node disease (24 [34.8%] had bacteriologic confirmation). The high overall
      bacteriologic yield indicates the need to reassess the value of bacteriology
      based approaches to diagnosis of intrathoracic tuberculosis in children,
      particularly in areas of endemicity where they frequently present with advanced
      disease.

PMID- 16575720
TI  - Aerosolized ribavirin-induced reversible hepatotoxicity in a hematopoietic stem
      cell transplant recipient with Hodgkin lymphoma.
AB  - We describe a case of acute hepatic toxicity associated with aerosolized
      ribavirin in a bone marrow transplant recipient with documented respiratory
      syncytial virus infection. The temporal relationship with drug administration and
      the liver biopsy results suggested drug-induced hepatic injury. As the use of
      aerosolized ribavirin to treat respiratory syncytial virus infections continues,
      it is imperative that careful attention be paid to possible adverse effects of
      therapy in the high-risk population of immunosuppressed patients.

PMID- 16575721
TI  - Mefloquine is highly efficacious against chloroquine-resistant Plasmodium vivax
      malaria and Plasmodium falciparum malaria in Papua, Indonesia.
AB  - BACKGROUND: During the period of 1996-1999, we prospectively monitored 243
      Javanese adults and children after arriving in Papua, Indonesia, and
      microscopically documented each new case of malaria by active surveillance.
      METHODS: In a randomized, open-label, comparative malaria treatment trial, 72
      adults and 50 children received chloroquine for each incident case of malaria,
      and 74 adults and 47 children received mefloquine. RESULTS: Among 975 primary
      treatment courses, the cumulative 28-day curative efficacies were 26% and 82% for
      chloroquine against Plasmodium falciparum malaria and Plasmodium vivax malaria,
      respectively. Mefloquine cure rates were far superior (96% against P. falciparum
      malaria and 99.6% against P. vivax malaria). CONCLUSIONS: Mefloquine is a useful
      alternative treatment for P. vivax malaria and P. falciparum malaria in areas
      such as Papua, where chloroquine is still recommended as the first-line
      therapeutic agent.

PMID- 16575722
TI  - Emerging chloroquine-resistant Plasmodium vivax (Benign Tertian) malaria: the
      need for alternative drug treatment.

PMID- 16575723
TI  - Efficacy of gentamicin plus doxycycline versus streptomycin plus doxycycline in
      the treatment of brucellosis in humans.
AB  - BACKGROUND: In the treatment of human brucellosis, antibiotic regimens containing
      an aminoglycoside are reportedly associated with fewer relapses. METHODS: This
      prospective, randomized study employed doxycycline (100 mg administered orally
      twice daily for 45 days) in combination with either streptomycin (1 g
      administered intramuscularly daily for 14 days; the DS regimen) or gentamicin (5
      mg/kg per day administered intramuscularly for 7 days; the DG regimen). Efficacy
      of treatment was determined by rates of failure or relapse with a follow-up
      period of 1 year. RESULTS: Ninety-seven patients with a mean age (+/- standard
      deviation [SD]) of 33.74+/-15.47 years and 94 patients with the a mean age (+/
      SD) of 36.2+/-14.14 years were treated with regimens DG and DS, respectively (P =
      .277). The clinical manifestations in both groups of patients were similar with
      the exception of sweating, which was more common in the DG group (P = .04). Three
      (3.2%) of the patients in the DS group and 3 (3.1%) of patients in the DG group
      experienced relapse (difference, 0.1%; 95% confidence interval [CI], -4% to 5%; P
      = 1.0). Overall, 7 (7.4%) of the patients in the DS group and 5 (5.2%) of the
      patients in the DG group experienced failure of therapy or relapse (difference,
      2.2%; 95% CI, -4.5% to 8.9%; P = .563). The actuarial probability for relapse at
      12 months after completion of therapy was 4.3% in the DS group and 2.1% in the DG
      group (difference, 2.2%; 95% CI, -2.8% to 7.2%). CONCLUSIONS: The combination of
      oral doxycycline for 45 days plus intramuscular gentamicin for 7 days is equally
      as effective as traditional therapy using doxycycline for 45 days plus
      streptomycin for 14 days.

PMID- 16575724
TI  - A randomized, double-blind clinical trial of a 3-week course of doxycycline plus
      albendazole and ivermectin for the treatment of Wuchereria bancrofti infection.
AB  - BACKGROUND: Eight- and 6-week courses of doxycycline are superior to standard
      treatment of bancroftian filariasis. Standard treatment (albendazole plus
      ivermectin) is associated with adverse reactions. We assessed whether a shorter
      (i.e, 3-week) course of doxycycline with standard treatment would show superior
      efficacy to standard treatment alone and reduce the incidence of adverse
      reactions. METHODS: A total of 44 adults from Ghana were recruited in January
      2003: 20 received doxycycline (200 mg/day) for 3 weeks, and 24 received matching
      placebo. Participants received albendazole (400 mg) and ivermectin (150
      microg/kg) at month 4, and adverse reactions were assessed 48 h later. Treatment
      efficacy was evaluated at months 4, 12, and 24. RESULTS: The microfilariae level
      was significantly reduced after receipt of doxycycline treatment at months 4 (P =
      .017), 12 (P = .001), and 24 (P = .005). The microfilariae level was only
      significantly reduced at month 12 in the placebo group (P = .041). At all follow
      up points, the microfilariae level was significantly lower in the doxycycline
      group. Adverse reactions to standard antifilarial treatment were similar in
      frequency between the doxycycline group (in 7 of 11 subjects) and the placebo
      group (in 13 of 17 subjects). Moderate reactions only occurred in the placebo
      group (in 3 of 17 subjects). Severity of adverse reaction was associated with
      microfilaremia (P = .037), Wolbachia bacteria in plasma (P = .048), and
      proinflammatory cytokines in plasma (P = .019). Adult parasite viability was not
      significantly different between doxycycline and placebo groups at months 12 or
      24. CONCLUSIONS: Treatment with doxycycline for 3 weeks is more effective in
      inducing a long-term amicrofilaremia than is standard treatment alone, but it is
      ineffective at inducing curative effects. Inflammatory reactions to antifilarial
      treatment are associated with levels of microfilariae and Wolbachia endosymbionts
      released into plasma.

PMID- 16575725
TI  - The promise of wolbachia-targeted chemotherapy as a public health intervention
      for lymphatic filariasis and onchocerciasis.

PMID- 16575726
TI  - Prior pneumococcal vaccination is associated with reduced death, complications,
      and length of stay among hospitalized adults with community-acquired pneumonia.
AB  - BACKGROUND: Vaccination with pneumococcal polysaccharide reduces the incidence of
      bacteremic pneumococcal disease in adults. We investigated the impact of prior
      pneumococcal vaccination on in-hospital mortality and the probability of
      respiratory failure among hospitalized adults with community-acquired pneumonia.
      METHODS: Consecutive individuals hospitalized with community-acquired pneumonia
      (diagnosed by International Classification of Diseases, Ninth Revision, Clinical
      Modification codes 480.0-487.0) at 109 community and teaching hospitals in the
      United States were identified using the Quality and Resource Management System, a
      database constructed by Tenet HealthCare to improve the quality of patient care.
      Vaccination status, comorbidities, and outcomes were abstracted by case managers
      concurrently with patient care. Associations between vaccination, survival, and
      respiratory failure were defined using multivariable logistic regression models.
      RESULTS: Of 62,918 adults hospitalized with community-acquired pneumonia between
      1999 and 2003, 7390 (12%) had a record of prior pneumococcal vaccination. Vaccine
      recipients were less likely to die of any cause during hospitalization than were
      individuals with no record of vaccination (adjusted odds ratio [OR], 0.50; 95%
      confidence interval [CI], 0.43-0.59), even after adjustment for the presence of
      comorbid illnesses, age, smoking, and influenza vaccination and under varying
      assumptions about missing vaccination data. Vaccination also lowered the risk of
      respiratory failure (adjusted OR, 0.67; 95% CI, 0.59-0.76) and other
      complications and reduced median length of stay by 2 days, compared with
      nonvaccination (P<.001). CONCLUSIONS: Prior vaccination against pneumococcus is
      associated with improved survival, decreased chance of respiratory failure or
      other complications, and decreased length of stay among hospitalized patients
      with community-acquired pneumonia. These observations reinforce current efforts
      to improve compliance with existing pneumococcal vaccination recommendations for
      adults.

PMID- 16575727
TI  - Safety profile of the viral vectors of attenuated fowlpox strain FP9 and modified
      vaccinia virus Ankara recombinant for either of 2 preerythrocytic malaria
      antigens, ME-TRAP or the circumsporozoite protein, in children and adults in
      Kenya.
AB  - BACKGROUND: We are developing a heterologous prime-boost vaccine strategy against
      malaria. This approach uses sequential immunization with different vectors to
      deliver a common preerythrocytic malaria antigen. Preliminary evidence of
      efficacy and safety has been previously documented in studies from an area where
      malaria is nonendemic. Additional safety data from an area where malaria is
      endemic are now required before larger-scale studies are undertaken to determine
      the efficacy of this vaccine strategy in the field. Other modified vaccinia virus
      Ankara (MVA) recombinants and prime-boost immunizations are being developed as
      vaccines against human immunodeficiency virus (HIV) infection, tuberculosis, and
      cancer, and MVA is a candidate attenuated smallpox vaccine. METHODS: Candidate
      vaccines against malaria were intradermally administered to 73 adults (7 of whom
      were HIV positive) and 22 children in Kenya. These vaccines used the attenuated
      fowlpox strain FP9 and the MVA recombinant for either of 2 preerythrocytic
      malaria antigens, multiple preerythrocytic-stage epitopes joined with the
      preerythrocytic-stage antigen TRAP (ME-TRAP) and the circumsporozoite protein
      (CS). Adverse events were recorded. RESULTS: Reactogenicity was mild. MVA caused
      less frequent and less severe cutaneous reaction if given after FP9 priming. Half
      doses reduced the frequency and the severity of systemic reactogenicity, and
      particular vaccine lots were associated with different reactogenicities.
      Unexpectedly, prior immunity to the ME-TRAP antigen appeared to be protective
      against local reactions after immunization. CONCLUSIONS: Where the final
      intention is to use MVA after FP9 priming, previous testing of MVA alone
      overestimates reactogenicity. These recombinant vectors appear to be safe and
      suitable for use in larger-scale studies of children in Africa and of HIV
      positive individuals.

PMID- 16575728
TI  - Linezolid-induced inhibition of mitochondrial protein synthesis.
AB  - BACKGROUND: Linezolid is an oxazolidinone antibiotic that is increasingly used to
      treat drug-resistant, gram-positive pathogens. The mechanism of action is
      inhibition of bacterial protein synthesis. Optic and/or peripheral neuropathy and
      lactic acidosis are reported side effects, but the underlying pathophysiological
      mechanism has not been unravelled. METHODS: We studied mitochondrial
      ultrastructure, mitochondrial respiratory chain enzyme activity, and
      mitochondrial DNA (mtDNA) in muscle, liver, and kidney samples obtained from a
      patient who developed optic neuropathy, encephalopathy, skeletal myopathy, lactic
      acidosis, and renal failure after prolonged use of linezolid. In addition, we
      evaluated mtDNA, respiratory chain enzyme activity, and protein amount in muscle
      and liver samples obtained from experimental animals that received linezolid or
      placebo. RESULTS: In the patient, mitochondrial respiratory chain enzyme activity
      was decreased in affected tissues, without ultrastructural mitochondrial
      abnormalities and without mutations or depletion of mtDNA. In the experimental
      animals, linezolid induced a dose- and time-dependent decrease of the activity of
      respiratory chain complexes containing mtDNA-encoded subunits and a decreased
      amount of protein of these complexes, whereas the amount of mtDNA was normal.
      CONCLUSION: These results provide direct evidence that linezolid inhibits
      mitochondrial protein synthesis with potentially severe clinical consequences.
      Prolonged courses of linezolid should be avoided if alternative treatment options
      are available.

PMID- 16575729
TI  - Excess risk of death from intensive care unit-acquired nosocomial bloodstream
      infections: a reappraisal.
AB  - BACKGROUND: Overall rates of bloodstream infection (BSI) are often used as
      quality indicators in intensive care units (ICUs). We investigated whether ICU
      acquired BSI increased mortality (by > or = 10%) after adjustment for severity of
      infection at ICU admission and during the pre-BSI stay. METHODS: We conducted a
      matched, risk-adjusted (1:n), exposed-unexposed study of patients with stays
      longer than 72 h in 12 ICUs randomly selected from the Outcomerea database.
      RESULTS: Patients with BSI after the third ICU day (exposed group) were matched
      on the basis of risk-exposure time and mortality predicted at admission using the
      Three-Day Recalibrated ICU Outcome (TRIO) score to patients without BSI
      (unexposed group). Severity was assessed daily using the Logistic Organ
      Dysfunction (LOD) score. Of 3247 patients with ICU stays of >3 days, 232
      experienced BSI by day 30 (incidence, 6.8 cases per 100 admissions); among them,
      226 patients were matched to 1023 unexposed patients. Crude hospital mortality
      was 61.5% among exposed and 36.7% among unexposed patients (P<.0001).
      Attributable mortality was 24.8%. The only variable associated with both BSI and
      hospital mortality was the LOD score determined 4 days before onset of BSI (odds
      ratio [OR], 1.10; 95% confidence interval [CI], 1.03-1.16; P = .0025). The
      adjusted OR for hospital mortality among exposed patients (OR, 3.20; 95% CI, 2.30
      4.43) decreased when the LOD score determined 4 days before onset of BSI was
      taken into account (OR, 3.02; 95% CI, 2.17-4.22; P<.0001). The estimated risk of
      death from BSI varied considerably according to the source and resistance of
      organisms, time to onset, and appropriateness of treatment. CONCLUSIONS: When
      adjusted for risk-exposure time and severity at admission and during the ICU
      stay, BSI was associated with a 3-fold increase in mortality, but considerable
      variation occurred across BSI subgroups. Focusing on BSI subgroups may be
      valuable for assessing quality of care in ICUs.

PMID- 16575730
TI  - The comparative accuracy of 8 commercial rapid immunochromatographic assays for
      the diagnosis of acute dengue virus infection.
AB  - BACKGROUND: The serological diagnosis of acute dengue virus infection relies on
      the detection of dengue-specific immunoglobulin M (IgM) antibodies.
      Immunochromatographic tests are rapid diagnostic tests (RDTs) that can be
      performed at the bedside, but they have not been fully validated for diagnosis of
      dengue infection. METHODS: More than 20 RDTs for diagnosis of acute dengue
      infection are commercially available. Of these, 8 were selected for evaluation of
      performance by use of characterized dengue and nondengue serum specimens, and
      results were compared with those of a previously published dengue IgM/IgG enzyme
      linked immunosorbent assay in conjunction with dengue virus serotyping by reverse
      transcriptase polymerase chain reaction. RESULTS: Assay sensitivities were low,
      ranging from 6.4% (95% confidence interval [CI], 4.0%-9.7%) to 65.3% (95% CI,
      59.9%-70.5%), and specificities ranged from 69.1% (95% CI, 61.4%-76.0%) to 100%
      (95% CI, 97.8%-100%). Of the 8 tests, only 2 had sensitivities of >50%, the level
      considered to be clinically useful, and, of these, 1 had relatively low
      specificity (69.1%). Samples collected early in the infection were less likely to
      test positive than those collected later. A thermal stability study demonstrated
      a loss in performance of some RDTs when they were stored at a high ambient
      temperature for 3 months. CONCLUSIONS: Users of RDTs for dengue should be aware
      that many of these tests have a diagnostic accuracy that falls well below the
      manufacturers' claims. If an acute specimen yields a negative result, a
      convalescent serum sample should be tested to confirm the result. No RDT
      adequately differentiated primary and secondary dengue infections, and the tests
      should not be used for this purpose.

PMID- 16575731
TI  - Microbiological diagnosis of empyema in children: comparative evaluations by
      culture, polymerase chain reaction, and pneumococcal antigen detection in pleural
      fluids.
AB  - BACKGROUND: Pleural empyema is an increasingly reported complication of pneumonia
      in children. Microbiological diagnostic tests for empyema by culture frequently
      have false-negative results due to previous administration of antibiotics.
      Molecular diagnosis by broad-range 16S ribosomal DNA (rDNA) polymerase chain
      reaction (PCR) and rapid pneumococcal antigen detection are reliable tools, but
      their diagnostic value has not been clearly established for pleural fluid
      samples. Pneumococcal antigen detection has only been validated for urine and
      cerebrospinal fluid samples. METHODS: Over 4 years, pleural fluid specimens were
      collected from 78 children with pleural empyema. Standard culture, pneumococcal
      antigen detection by latex agglutination (Pastorex; Bio-Rad) and
      immunochromatographic testing (Binax NOW Streptococcus pneumoniae), and 16S rDNA
      PCR were performed on these specimens. Pneumococcal identification by 16S rDNA
      PCR and sequencing was confirmed by pneumolysin PCR. RESULTS: Of the 78 cases of
      pleural empyema, 60 (77%) were microbiologically documented by culture or 16S
      rDNA PCR. Of the 40 pneumococcal empyema cases, 17 (43%) were only diagnosed by
      PCR and 23 with PCR and culture. The sensitivity and specificity of the latex
      antigen detection (with the use of culture and/or PCR as the test standard) were
      90% and 95%, respectively. The immunochromatographic test detected pneumococcal
      antigens in 3 additional specimens for which latex agglutination results were
      negative, thereby increasing the sensitivity of antigen detection. CONCLUSIONS:
      Pneumococcal antigen detection in pleural fluid specimens from children provides
      a rapid and sensitive method of diagnosis of pneumococcal empyema, which can be
      confirmed by specific pneumolysin PCR when culture results are negative. Broad
      range 16S rDNA PCR has value in detecting bacterial agents responsible for
      culture-negative pleural empyema.

PMID- 16575732
TI  - Point: mandatory influenza vaccination for all heath care workers? Seven reasons
      to say "no".

PMID- 16575733
TI  - Counterpoint: in favor of mandatory influenza vaccine for all health care
      workers.

PMID- 16575734
TI  - Changes in the age-specific prevalence of hepatitis A virus antibodies: a 10-year
      cohort study in Jinju, South Korea.
AB  - The changing patterns in seroprevalence rates of hepatitis A virus antibodies
      among children and adolescents from 1988 to 1997 reflect the cohort effects that
      occurred over 10 years in South Korea. Our results suggest that the majority of
      adolescents and young adults are at risk of symptomatic hepatitis A virus
      infection and morbidity.

PMID- 16575735
TI  - Global changes in the epidemiology of hepatitis A virus infections.

PMID- 16575736
TI  - Macrolide prescriptions and erythromycin resistance of Streptococcus pyogenes.
AB  - This study shows a significant association between the number of macrolide
      prescriptions reimbursed by the Italian National Health Service and resistance of
      Streptococcus pyogenes to erythromycin in children from a region in northern
      Italy with high prevalence of erythromycin resistance. Recent prescription of a
      macrolide (especially azithromycin) is a predictor of erythromycin resistance, as
      well as a possible risk factor for resistance at a community level.

PMID- 16575737
TI  - Efficacy of safety-engineered device implementation in the prevention of
      percutaneous injuries: a review of published studies.
AB  - Nearly 6 years have passed since the Needlestick Safety and Prevention Act of
      2000 was signed into law. We reviewed studies published since 1995 that evaluated
      the effect of safety-engineered device implementation on rates of percutaneous
      injury (PI) among health care workers. Criteria for inclusion of studies in the
      review were as follows: the intervention used to reduce PIs was a needleless
      system or a device with engineered sharps-injury protection, the outcome
      measurements included a PI rate, the intervention was evaluated in a defined
      population with clear comparison groups in clinical settings, and outcomes and
      denominators used for rate calculations were objectively measured using
      consistent methodology. All 17 studies reported substantial decreases in device
      associated or overall PI rates after device implementation (range of reduction,
      22%-100%). The majority of studies (n=12) were uncontrolled before-after trials
      with limited ability to control for confounding variables. In addition,
      implementation of safety-engineered devices was often accompanied by other
      interventions, and direct measurement of outcomes was not performed.
      Nevertheless, safety-engineered devices are an important component in PI
      prevention.

PMID- 16575738
TI  - Micafungin: a new echinocandin.
AB  - Micafungin, a potent inhibitor of 1,3-beta-D-glucan synthase, has become the
      second available agent in the echinocandins class that is approved for use in
      clinical practice. This agent shares with caspofungin an identical spectrum of in
      vitro activity against Candida albicans, non-albicans species of Candida, and
      Aspergillus species, as well as several but not all pathogenic molds. If
      anything, its in vitro activity appears to be superior to that of caspofungin,
      although the clinical relevance of this observation is unclear. The clinical role
      of micafungin appears to be similar to that of caspofungin, although clinical
      data are still lacking at this stage, with initial approval only for treatment of
      esophageal candidiasis and prophylaxis in subjects with neutropenia.
      Pharmacokinetic and pharmacodynamic studies and reports of adverse effects and
      safety have reported similar but not identical results to those of other agents
      in the echinocandin class. Factors such as acquisition costs and the potential
      for resistance development may be more relevant to its widespread use than in
      vitro and in vivo data comparisons with caspofungin.

PMID- 16575739
TI  - A multicenter randomized trial evaluating posaconazole versus fluconazole for the
      treatment of oropharyngeal candidiasis in subjects with HIV/AIDS.
AB  - BACKGROUND: Oropharyngeal candidiasis is the most common opportunistic infection
      among persons infected with human immunodeficiency virus (HIV). Use of some
      agents is hampered by lack of efficacy, emergence of resistance, adverse events,
      and need for intravenous administration. Posaconazole is an extended-spectrum
      triazole with potent in vitro activity against Candida species, including Candida
      albicans, Candida glabrata, and Candida krusei (including fluconazole-resistant
      strains). METHODS: This multicenter, randomized, evaluator-blinded study of
      subjects with HIV infection and oropharyngeal candidiasis compared efficacy of
      posaconazole with that of fluconazole. Subjects received either 200 mg of
      posaconazole or fluconazole oral suspension on day 1, followed by 100 mg/day for
      13 days. The primary study end point--clinical success (cure or improvement) on
      day 14--was evaluated for 329 subjects. Durability of clinical success was
      evaluated on day 42. RESULTS: Three hundred fifty subjects received posaconazole
      (n = 178) or fluconazole (n = 172). Clinical success occurred in 155 (91.7%) of
      169 posaconazole recipients and in 148 (92.5%) of 160 fluconazole recipients (95%
      confidence interval, -6.61% to 5.04%), indicating that posaconazole was not
      inferior to fluconazole. On day 14, mycological success was 68% in both arms, but
      by day 42, significantly more posaconazole recipients than fluconazole recipients
      continued to have mycological success (40.6% vs. 26.4%; P=.038). Fewer
      posaconazole recipients than fluconazole recipients experienced clinical relapse
      (31.5% vs. 38.2%). Adverse events were similar between treatment arms.
      CONCLUSIONS: Results demonstrate that posaconazole was as effective as
      fluconazole in producing a successful clinical outcome. However, posaconazole was
      more effective in sustaining clinical success after treatment was stopped.

PMID- 16575740
TI  - Oropharyngeal candidiasis: a new treatment option.

PMID- 16575742
TI  - Can responses to antiretroviral therapy be improved by therapeutic drug
      monitoring?

PMID- 16575741
TI  - Marked intraindividual variability in antiretroviral concentrations may limit the
      utility of therapeutic drug monitoring.
AB  - BACKGROUND: Effective therapeutic drug monitoring for antiretrovirals requires a
      better understanding of intraindividual variability in pharmacokinetics. METHODS:
      We determined concentrations of human immunodeficiency virus (HIV) protease and
      nonnucleoside reverse-transcriptase inhibitors for 10 patients with undetectable
      plasma HIV RNA levels who had been receiving stable regimens for > or = 11
      months. Plasma samples were collected at the same time of day 3 times per week
      for up to 4 months. Patients were instructed to take their antiretrovirals at the
      same time every day. Plasma protease and nonnucleoside reverse-transcriptase
      inhibitor concentrations were determined using high-performance liquid
      chromatographic methods. Pharmacokinetic variability was expressed as
      intraindividual percentage coefficient of variation (ICV), which was calculated
      as the patient's standard deviation divided by the mean drug concentration for
      that patient. RESULTS: ICV was determined for 6 drugs for 10 patients, for a
      total of 17 different patient-drug combinations, using 600 total samples. ICV was
      unexpectedly high for most patients who were receiving protease inhibitors (ICVs
      for individual patients taking lopinavir/ritonavir were 24%, 33%, 51%, and 92%;
      for patients taking nelfinavir/M8 metabolite, they were 30%/44% and 39%/54%; for
      patients taking ritonavir, they were 34% and 43%; for patients taking saquinavir,
      they were 52% and 55%). ICVs for patients receiving nonnucleoside reverse
      transcriptase inhibitors were lower (for patients receiving efavirenz, they were
      7%, 13%, 29%, and 51%; for a patient receiving nevirapine, it was 25%). The
      median ICV for all patients receiving protease inhibitors (n = 12) was 43.5%, and
      for all patients receiving nonnucleoside reverse-transcriptase inhibitors (n =
      5), the median ICV was 25%. CONCLUSIONS: Intraindividual variability in
      concentrations of antiretrovirals was surprisingly high in virologically
      suppressed patients. Possible contributors include food effects, concomitant use
      of prescription and herbal medications, assay variability, or medication timing,
      which was assessed by self-report. High intraindividual pharmacokinetic
      variability may limit the utility of single measurements in therapeutic drug
      monitoring for some antiretroviral agents.

PMID- 16575743
TI  - Vancomycin-resistant enterococcal bloodstream infection-related mortality: focus
      on the lack of appropriate therapy.

PMID- 16575744
TI  - Reply to Nannini and to a previous letter by Hurley.

PMID- 16575745
TI  - A clinically dangerous flaw in reporting statistical significance.

PMID- 16575747
TI  - Spontaneous rupture of the spleen during malaria: a conservative treatment is
      appropriate for selected patients.

PMID- 16575748
TI  - Pneumocystis carinii nomenclature: response to Cushion and Stringer.

PMID- 16575749
TI  - Pneumocystis carinii nomenclature: 2 misnomers are not better than 1.

PMID- 16575750
TI  - Pneumocystis nomenclature.

PMID- 16575751
TI  - Pneumocystis carinii versus Pneumocystis jirovecii (jiroveci) Frenkel.

PMID- 16575753
TI  - Safety of artemisinin antimalarials.

PMID- 16575754
TI  - Is Clostridium difficile the leading pathogen in bacterial diarrhea in HIV type 1
      infected patients?

PMID- 16575756
TI  - The effects of melatonin, N-acetylserotonin, and 6-hydroxymelatonin on the
      ultrastructure of the pinealocytes of the Syrian hamster (Mesocricetus auratus).
AB  - OBJECTIVES: The aim of this study was to examine the effects of melatonin as well
      as of its precursor (N-acetylserotonin) and metabolite (6-hydroxymelatonin) on
      the ultrastructure of the pinealocytes of the Syrian hamster. MATERIAL AND
      METHODS: The pineal glands of 2-month-old male Syrian hamsters were examined. The
      animals were divided into the following groups of four animals each: group 1 -
      melatonin treatment; group 2 - N-acetylserotonin treatment; group 3 - 6
      hydroxymelatonin treatment (all substances given subcutaneously at doses of 25
      microg per animal between 16.00 and 17.00 h daily for seven weeks). Group 4 was
      given solvent treatment only and served as controls. The animals were killed by
      decapitation between 09:00 and 10.00 h. Routine electron microscopical techniques
      were used to obtain quantitative data on pinealocyte ultrastructure. RESULTS:
      Melatonin administration did not influence the size of the hamster pinealocytes,
      whereas administration of N-acetylserotonin and 6-hydroxymelatonin caused a
      significant reduction in cell size in comparison to the melatonin-treated and
      control groups. There were changes in the relative volumes of the mitochondria,
      Golgi apparatus and lysosomes in the pinealocytes of the studied groups, while
      the volumes of granular endoplasmic reticulum and lipid droplets were unchanged.
      The dense-core vesicles were more numerous in the pinealocytes of the melatonin
      and 6-hydroxymelatonin-treated groups in comparison to those of animals treated
      with N-acetylserotonin or the controls. CONCLUSIONS: The changes observed in the
      ultrastructure of hamster pinealocytes indicate that administration of melatonin
      as well as of its precursor or metabolite influences the morphology of these
      cells and also, perhaps, their secretory activity.

PMID- 16575757
TI  - [Influence of pinealectomy and long-term melatonin administration on bone
      metabolism in orchidectomized rats].
AB  - INTRODUCTION: The aim of the study was to demonstrate whether pinealectomy and
      long-term MEL administration can affect bone metabolism (as evaluated on the
      basis of serum concentrations of PICP and ICTP) in orchidectomized rats. MATERIAL
      AND METHODS: The study included 248 adult male Wistar rats; 6 remained intact,
      120 were orchidectomized (Orch), and the remaining ones underwent a sham
      operation (SOrch). Two weeks after surgery, the rats were divided into 8 groups:
      1) SOrch + SPx; 2) SOrch + SPx + MEL; 3) Orch + SPx; 4) Orch + SPx + MEL; 5)
      SOrch + Px; 6) SOrch + Px + MEL; 7) Orch + Px; 8) Orch + Px + MEL. Animals from
      5(th), 6(th), 7(th) and 8(th) groups were pinealectomized (Px) while the
      remaining ones underwent a sham operation (SPx). Two weeks after surgery rats in
      the 2(nd), 4(th), 6(th) and 8(th) groups were administered MEL (50 microg/100 g
      of bm) intraperitoneally while the remaining animals were administered solvent
      only (daily between 5 and 6 pm during a month). The animals were decapitated
      before the experiment (intact rats), after 2 weeks from Orch and SOrch, Px and
      SPx, after 4 weeks from MEL or solvent administration and after 4 and 8 weeks
      from discontinuing administration of MEL, and blood was collected for PICP and
      ICTP concentrations assays with the use of RIA method. DISCUSSION: In Orch rats,
      a distinct tendency to increase the studied bone markers, especially ICTP was
      shown. Pinealectomy had inducing, while MEL suppressing effect upon the level of
      PICP and ICTP; these changes were more pronounced in Orch + Px and SOrch + Px +
      MEL groups, respectively. After discontinuing administration of MEL distinct
      tendency to increase of PICP and ICTP level was shown. CONCLUSIONS: Our findings
      indicate that MEL is an important modulator of bone tissue metabolism in male
      rats and that deficiency of MEL concentration may be a co-factor in osteoporosis
      development.

PMID- 16575758
TI  - The relation of serum adiponectin and leptin levels to metabolic syndrome in
      women before and after the menopause.
AB  - INTRODUCTION: It is well known that there is a higher prevalence of
      cardiovascular risk factors and metabolic syndrome (MS) in postmenopausal women.
      Recently it has become evident that adiponectin and leptin secreted by adipose
      tissue may be involved in the pathophysiology of MS. THE AIM OF THE STUDY: was to
      assess the effects of the menopause on the relationships between adiponectin and
      leptin and different cardiovascular and metabolic risk factors. MATERIALS AND
      METHODS: A total of 56 postmenopausal women and 75 premenopausal subjects were
      enrolled in this study. We measured blood pressure, BMI, waist circumference and
      WHR, triglycerides (TG), high density lipoprotein cholesterol (cHDL) levels and
      fasting glucose and applied the oral glucose tolerance test (OGTT). Women were
      categorised as having 0, 1, 2, 3 or more risk factors. The presence of at least 3
      abnormalities was defined as MS. Serum was assayed for adiponectin and leptin by
      the radioimmunoassay (RIA) method. RESULTS: A decline in adiponectin was related
      to an increased number of MS variables in postmenopausal and premenopausal women.
      Postmenopausal women with MS had significantly lower adiponectin concentrations
      than premenopausal women with MS. Serum adiponectin concentrations were inversely
      correlated to leptin in postmenopausal women. In premenopausal women no clear
      relationships were found between serum leptin and the number of metabolic
      disturbances. In contrast to young women, postmenopausal women showed an increase
      in leptin secretion with a growing number of MS elements. Compared to
      premenopausal women with MS, postmenopausal women with MS had higher levels of
      leptin. We found associations between leptin and different risk factors, mainly
      in the postmenopausal group. When the presence of MS was used as a dependent
      variable (yes/no) and adiponectin, leptin and menopause status as independent
      factors, adiponectin and leptin remained significant variables related to MS.
      CONCLUSION: The significant role of adiponectin in the pathophysiology of MS in
      premenopausal and postmenopausal women is confirmed in this study. Leptin is
      correlated with several MS components but this adipocytokine appears to play a
      role only in postmenopausal women.

PMID- 16575759
TI  - [Correlation between thyroid stimulating immunoglobulins and thyrotropin binding
      inhibitory immunoglobulins levels in patients with Graves' disease].
AB  - INTRODUCTION: The II generation method using human recombination thyrotropin
      receptors for measurement of thyrotropin binding inhibitory immunoglobulins
      (TBII) is characterized by increased sensitivity and specificity in comparison
      with I generation method. AIM OF STUDY was to determine, whether TBII levels
      measured with II generation assay reflect thyroid stimulation and whether
      measurement of thyroid stimulating antibodies (TSI) could be replaced by TBII
      determinations. Specific aim was to evaluate, whether correlation between TSI and
      TBII levels is stable during antithyroid therapy. MATERIAL AND METHODS: 41
      patients with the newly diagnosed Graves' disease were included in the study. TSI
      (cAMP levels in CHO cell line) and TBII (II generation assay) levels were
      determined before treatment and after 1, 3, 6, 9 and 12 months of thiamazol
      therapy. Moreover, thyroid blocking antibodies were determined after 12 months of
      treatment. RESULTS: 32 patients (82.05%) had positive basic TSI level and 35
      patients (89.74%) had positive basic TBII level. After 12 months of therapy
      negative level of TSI was observed in 67.57% of patients and negative level of
      TBII was founded in 45.85% of patients. Correlation between TSI and TBII levels
      was positive during treatment course except time after 9 months of therapy.
      CONCLUSIONS: TBII level is adequate parameter to assess thyroid stimulation
      intensity. Positive correlation between TSI and TBII levels is present during
      almost whole treatment course. TBII seems to be reliable parameter in disease
      activity monitoring and response to therapy.

PMID- 16575760
TI  - [Five year remission of GHRH secreting bronchial neuroendocrine tumor with
      symptoms of acromegaly. Utility of chromogranin A in the monitoring of the
      disease].
AB  - Acromegaly is usually caused by excess GH (growth hormone) secretion by pituitary
      adenoma. Extremely rare (< 1% of cases) acromegaly can be a result of ectopic
      GHRH (growth hormone releasing hormone) secretion by bronchial tubes, lung,
      pancreatic or intestinal tumor. The aim of this description is to present the
      case of successfully treated acromegaly caused by ectopic GHRH secretion by
      bronchial neuroendocrine tumor and the usefulness of chromogranin A assay in the
      disease monitoring. The diagnosis of acromegaly in 61-year old woman was based on
      typical clinical picture and elevated GH and IGF-1(insulin-like growth factor-1)
      levels. MRI (magnetic resonance imaging) images revealed no tumor in the
      pituitary but only the pituitary enlargement. Moreover, the right lung tumor (10
      cm size) and elevated GHRH level were documented. The secretion of GH, IGF-1 and
      GHRH were normalized and progression of acromegaly was stopped after the
      carcinoid tumor surgery. Currently, 5 year after surgery, acromegaly is still in
      the remission, as the normal levels of GH, IGF-1, chromogranin A and normal chest
      and pituitary images confirm. The authors emphasize usefulness of measurement of
      chromogranin A concentration for the evaluation of the tumor remission in case
      the routine GHRH assay is not accessible.

PMID- 16575761
TI  - [The effect of Chernobyl accident on the development of non malignant diseases].
AB  - The early medical complications of Chernobyl accident include post radiation
      disease, which were diagnosed in 134 subjects affected by ionizing radiation. 28
      persons died during the first 100 days after the event. The increase occurrence
      of coronary heart disease, endocrine, haematological, dermatological and other
      diseases were observed after disaster in the contaminated territories. We also
      discussed the impact of ionizing radiation from Chernobyl accident on pregnancy
      and congenital defects occurrence. Changes following the Chernobyl accident, as
      the inhabitants migration from contaminated regions, political and economic
      conversions, led to depression, anxiety, and even to "epidemic" of mental
      diseases. Increased suicide rate, car accidents, alcohol and drug abuse have been
      observed in this population. Nowadays vegetative neurosis is more often diagnosed
      in Ukrainian children. Epidemiological studies were conducted on the ionising
      radiation effect on the health and on the dose of received radiation after
      Chernobyl accident face numerous problems as the absence of reliable data
      regarding diseases in the contaminated territories.

PMID- 16575763
TI  - [Pheochromocytoma - chromaffin cell tumor].
AB  - Pheochromocytoma is a rare tumor derived from chromaffin cells, which produces
      catecholamins. The presence of this tumor is considered a cause of secondary
      hypertension, arrhythmias, sweating and also, but very rarely, mental disorders.
      Update diagnostic methods of pheochromocytoma are summarized in this article.
      Pheochromocytoma also coexists with endocrinological syndroms, e.g. multiple
      endocrine neoplasia type 2 (MEN 2). Studies confirm genetic background of
      pheochromocytoma occurrence.

PMID- 16575762
TI  - [The radiological situation before and after Chernobyl disaster].
AB  - The nuclear reactor accident, which occurred on 26 April 1986 at Chernobyl, has
      been one of the greatest ecological disasters in human history. In our study we
      discussed the most recent data on the accident, and the natural and synthetic
      sources of radiation. According to the recent data, the air at Chernobyl had been
      contaminated with about 5300 PBq radionuclide activity (excluding rare gases),
      including 1760 PBq (131)I and 85 PBq (137)Cs. The highest radiation received by
      the liquidators (0.8-16 Gy), lower doses were received by the population which
      was evacuated or inhabited the contaminated areas (in which the level of (137)Cs
      activity deposited in the earth was 37 kBq/m(2)). In the European countries the
      highest mean radiation dose per year for the whole body in the first year after
      the accident was in Bulgaria (760 microSv), Austria (670 microSv) and Greece (590
      microSv), while the lowest radiation dose was observed in Portugal (1.8 microSv)
      and Spain (4.2 microSv). In Poland the mean effective equivalent dose resulting
      from Chernobyl accident was 932 microSv and is close to the limited dose
      permitted in Poland, equalling 1 mSv/year. The highest radiation dose to thyroid
      was received by inhabitants of the states previously known as Bielskopodlaskie,
      Nowosadeckie and the north-east region of Poland. Lowest dose was received by
      inhabitants of the areas previously known as Slupski and Rzeszowski.

PMID- 16575764
TI  - [Abstracts from the 1st Polish Conference on Neuroendocrine Digestive System
      Tumors, Warsaw, Poland, April 2005].

PMID- 16575766
TI  - [Acute onset ataxia in infancy: its aetiology, treatment and follow-up].
AB  - INTRODUCTION: Acute childhood ataxia is a cause of referency to the pediatric
      emergency room. AIM. To characterize the etiology, clinical picture, management,
      and outcome of acute ataxia in our hospital. PATIENTS AND METHODS: A prospective
      study was undertaken including 39 children with acute ataxia who were admitted
      between January 1, 2001 and December 31, 2003. RESULTS: During the study period
      159,002 episodes were evaluated, 39 children (0.024%) with acute ataxia. The most
      common diagnoses were post-infectious ataxia (51.2%) and toxic exposure (25.6%).
      The mean age at presentation in post-infectious ataxia was 55 +/- 27.61 months,
      60% females. A prodromal febrile illness was noted in 95%: varicella (10),
      nonspecific viral infection (6), mycoplasma, enterovirus, and Epstein-Barr virus.
      The latency from the prodromal illness to the onset of ataxia was 5.86 +/- 3.78
      days. Lumbar punctures were altered in 11/17. All computed tomography scans
      performed were normal. At follow up, one boy presented asymmetric signs of
      cerebellar dysfunction secondary to hemicerebellitis. The media of the patient
      who showed full-gait recovery was 18 days, and was complete in all children,
      except one boy who presented hemophagocytic lymphohistiocytosis. Toxic ingestion
      was the second most common cause. Boys less than 6 years were more commonly
      affected. CONCLUSIONS: Acute childhood ataxia are an uncommon cause of
      presentation to our pediatric emergency room. Postinfectious ataxia and drug
      ingestion are the most common diagnosis, with a usually benign and self-limited
      process. A thorough history and neurology examination should be guided to
      etiology. Neuroimaging studies and hospitalization are needed only if atypical
      presentation, asymmetric neurologic examination and prolonged ataxia.

PMID- 16575767
TI  - [Hypothalamo-pituitary axis: effects of physical training in rats administered
      with dexamethasone].
AB  - AIM: To investigate the effects of physical training associated to dexamethasone
      administration in carbohydrate metabolism and adrenocorticotrophic hormone (ACTH)
      release. MATERIALS AND METHODS: Young Wistar rats were divided into four groups:
      sedentary control (CS), sedentary dexamethasone (DxS), trained control (CT) and
      trained dexamethasone (DxT). The rats were submitted to swimming training
      associate to administration of dexamethasone for ten weekends. Before sacrifice
      the rats received subcutaneous insulin to calculate the maximum decreased in
      blood glucose. Venous blood was sampled obtained at the end experiment period to
      determine glucose, insulin, free fatty acids (FFA) and ACTH. Gastrocnemius and
      liver tissue samples were used to determination glycogen, and adipose epididymal
      tissue was used to measured the weight. RESULTS: Dexamethasone administration
      provoke insulin resistance and the physical training reverted this aspect.
      Training promoted increase in muscle and liver glycogen store and a high
      utilization of FFA. Moreover, the dexamethasone provoke decreased of ACTH release
      in response to acute exercise, showing marked differences in the functioning of
      the hypothalamy-pituitary-adrenal (HPA) axis between groups of rats. CONCLUSIONS:
      a) Low-dose of dexamethasone promote several side effects in metabolism
      intermediary and chronic exposure to steroid was associated with insulin
      resistance; b) The regular swimming exercise promoted increased insulin
      sensitivity. Therefore, exercise can override the dexamethasone negative feedback
      of the HPA axis activation in rats.

PMID- 16575768
TI  - [Intramuscular midazolam in the initial treatment of status epilepticus].
AB  - INTRODUCTION: The status epilepticus a serious complication of the epileptic
      syndrome with high rates of morbidity and mortality. Treatment is aimed to a fast
      control of the crisis. AIM: To evaluate the efficacy and security of
      intramuscular (IM) midazolam in the initial treatment of status epilepticus.
      PATIENTS AND METHODS: A prospective open clinical trial that included 43 status
      epilepticus in 38 adult patients. All of the cases received an initial dose of 15
      mg IM of midazolam, with a simultaneous oral dose of phenytoin (15 to 20 mg/kg)
      or carbamazepine (15 mg/kg). If there was immediate control of the seizure but
      recurrence occurred during the next hours, 15 mg im of midazolam every 8 hours
      were given, for 24 hours. If there was immediate failure intravenous (IV)
      midazolam was given. RESULTS: 36 of the 43 status epilepticus were controlled: 30
      with only one dose, 3 required additional IM doses, and 3 needed administration
      of IV midazolam, no patient had neither cardiovascular, respiratory or local
      complications. The only adverse effect was drowsiness in a variable grade.
      CONCLUSIONS: The use of IM midazolam is suggested as the initial treatment in
      status epilepticus in adults, especially in a low complexity setting, due to its
      effectiveness, quick action and security.

PMID- 16575770
TI  - [Management and predictors in patients with spontaneous intracerebral
      hemorrhage].
AB  - AIM: To review about novel aspects in the initial management of patients with
      spontaneous intracerebral hemorrhage (SICH) and to analyze a group of predictors
      with influence on the election of certain therapies and on the 30-day mortality.
      DEVELOPMENT: SICH often constitutes a critical illness. Thus, many SICH patients
      are admitted in intensive care units (ICUs) for continuous monitoring and
      'appropriate' treatment. In these settings it is essential to have predictors of
      poor outcome to plan the level of care and to optimize resource utilization.
      Clinical management of these patients focuses on controlling the intracranial
      pressure, stopping or slowing the hematoma expansion, limiting the secondary
      injury and preventing medical complications. CONCLUSIONS: The 30-day mortality of
      SICH remains dismal (42%) despite modern ICUs. Recent prognostic studies have
      brought new insights about various SICH predictors, but even so there are still
      several unanswered questions. Treatment for this hemorrhagic stroke is primarily
      supportive, although recombinant factor VIIa may represent the first proven
      treatment for SICH.

PMID- 16575769
TI  - [Embryopathy due to valproic acid with severe malformations in the central
      nervous system].
AB  - INTRODUCTION: Embryogenetic disorders are one of the most serious problems in the
      life of an epileptic. Over the last few decades many antiepileptic drugs,
      including valproic acid, have been shown to have teratogenic properties.
      Embryopathy due to valproate, also known as fetal valproate syndrome, is a well
      known and documented example of these conditions. CASE REPORT: We report the case
      of a preterm newborn infant who, at birth, exhibited a syndrome characterised by
      facial dysmorphia, gingival hyperplasia, neurological hyperexcitability and
      multiple malformations, the most striking of which was the presence of
      predominantly temporal atrophy in the left brain hemisphere. The most significant
      event in the medical history of the case was the mother's taking valproate in
      monotherapy throughout the entire period of gestation as treatment for
      generalised idiopathic epilepsy that was diagnosed during adolescence. Screening
      precluded the most common metabolic, hereditary or infectious causes that can
      cause embryopathies. CONCLUSIONS: The mother's history of taking valproic acid
      and the specific findings that coincided in the peculiar embryopathy of this
      patient enabled us to link them.

PMID- 16575771
TI  - [Neurotransmitters in Alzheimer's disease].
AB  - AIM: To review the current state of the art in neurotransmission in Alzheimer's
      disease (AD) and its involvement in the pathophysiology of the disease.
      INTRODUCTION: AD is a neurodegenerative disorder that is estimated to affect 15
      million people around the world. Since the cholinergic hypothesis of AD was put
      forward 20 years ago, numerous studies have been conducted in an attempt to
      determine the role that neurotransmitters play in AD. Among other things, this
      has made it possible to develop drugs based on the inhibition of
      acetylcholinesterase. DEVELOPMENT: The monoaminergic neurotransmission systems
      are examined, with special attention given to the cholinergic system, and their
      anatomical distribution, function, receptors, activity and degradation systems
      are also described. Peptidergic neurotransmission systems are only briefly
      discussed, since they are not the main objective of this report. We also review
      the cholinergic hypothesis and the possible interrelations between cholinergic
      neurotransmission and beta-amyloid metabolism, as well as the potential
      involvement of acetylcholinesterase inhibitor drugs in more fundamental
      pathophysiological mechanisms, which act with a neuroprotective component.

PMID- 16575772
TI  - [Neuropeptides in Alzheimer's disease].
AB  - INTRODUCTION: Of approximately 200 peptides that are known to exist in the body,
      80 carry out functions as neurotransmitters and about 20 have been linked to
      Alzheimer's disease (AD). DEVELOPMENT: In this article we review the most salient
      studies that have been conducted on neuropeptides such as corticotropin-releasing
      hormone, thyrotropin-releasing hormone, somatostatin, neuropeptide Y, oxytocin,
      arginine vasopressin, galanin and insulin, as well as the insulin-like growth
      factors, the glucagon-like peptides, vasoactive intestinal peptide,
      cholecystokinin, substance P, opioid peptides and the neuropeptide NAP. Although
      attempts are made to find a causal association with AD, in many cases the
      findings are contradictory or not very conclusive. CONCLUSIONS: The most notable
      points could be the reduction in substance P in the cerebral cortex, hippocampus,
      basal ganglia and cephalospinal fluid; the diminished levels of somatostatin in
      the same structures except for the basal ganglia; the reduction in the amount of
      vasopressin except in the temporal lobe; and the increased levels of dynorphin
      and leucine enkephalin.

PMID- 16575773
TI  - [A longitudinal study of patients with Parkinson's disease (ELEP): aims and
      methodology].
AB  - INTRODUCTION AND DEVELOPMENT: Parkinson's disease (PD) is a chronic and
      progressive disorder. It produces a significant burden not only for patients, but
      also for their family and caregivers, with a major socio-economic impact on
      society. Current knowledge on PD is characterized by scarce information about the
      evolutionary course of: 1) the non-motor PD features; 2) impact of non-motor PD
      features on disability and health related quality of life (HRQL) impairment; 3)
      factors related to disability and HRQL determinants; 4) factors that speed or
      slow the progression of PD; 5) differential long-term effect of available PD
      therapeutic schedules and their relationships with disability, complications, and
      HRQL; and 6) impact of the disease on patients' caregivers. In addition,
      heterogeneity in the metric quality of the applied measures and selection bias
      are frequently found. CONCLUSION: Due to the aforementioned limitations and from
      a multidimensional perspective, a new longitudinal study in PD is deemed
      necessary. The longitudinal study of PD patients (ELEP) includes a long-term
      follow-up of never before systematically assessed aspects, will allow to increase
      the global knowledge about PD.

PMID- 16575774
TI  - [Neuroradiological findings in monostotic fibrous dysplasia].

PMID- 16575776
TI  - [Sexual headaches associated to an arachnoid cyst].

PMID- 16575777
TI  - [Transient global amnesia during sexual intercourse].

PMID- 16575778
TI  - [The diagnosis and treatment of children with arachnoid cysts associated to mild
      traumatic brain injury].

PMID- 16575779
TI  - An effective derivatization method for matrix-assisted laser
      desorption/ionization mass spectrometry of poly(acrylic acid).

PMID- 16575780
TI  - Investigation of the electrochemical oxidation products of zotepine and their
      fragmentation using on-line electrochemistry/electrospray ionization mass
      spectrometry.
AB  - When zotepine, an antipsychotic drug, was electrochemically oxidized using
      electrospray ionization mass spectrometry (ESI-MS) coupled with a microflow
      electrolytic cell, [M + 16 + H]+ (m/z 348), [M-H]+ (m/z 330) and [M-14 + H]+ (m/z
      318) were observed as electrochemical oxidation product ions (M represents the
      zotepine molecule). Although a major fragment ion that was derived from the
      dimethyl aminoethyl moiety was observed only at m/z 72 in the collision-induced
      dissociation (CID) spectrum of zotepine, new fragments such as m/z 315 and 286
      ions could be generated in the CID spectrum by combining electrochemical
      oxidation and CID. Since these fragments were relatively specific with high ion
      strength, it was thought that they would be useful for developing a sensitive LC
      MS/MS assay. The S-oxide and N-demethylated products were detected by
      electrolysis assuring that a portion of P450 metabolites of zotepine could be
      mimicked by the electrochemistry/electrospray ionization mass spectrometry
      (EC/ESI-MS) system.

PMID- 16575781
TI  - Blue natural organic dyestuffs--from textile dyeing to mural painting. Separation
      and characterization of coloring matters present in elderberry, logwood and
      indigo.
AB  - Natural dyestuffs used for painting or dyeing of textiles are complex mixtures of
      compounds of various chemical properties. Proper identification of the dye used
      by a painter and, even better, its origin is possible only when its compositional
      'fingerprint' can be evaluated. For this reason gradient program for liquid
      chromatographic separation of 16 color compounds--components of natural blue
      dyes: elderberry, logwood and indigo--has been developed. Two detector systems
      were used simultaneously: UV-Vis spectrophotometry (at 280, 445, 520 and 600 nm)
      and ESI mass spectrometry (positive and negative SIM mode). It was found that
      fragmentation observed in ESI-MS is affected not only by ion source parameters,
      but also by chromatographic conditions, especially in case of the less stable
      substances: cyanidin glucosides, tannic acid, rutin and hematoxylin. Examination
      of characteristic dissociation pathways of the compounds under investigation
      after direct admission into ion source or after chromatographic separation
      allowed to select proper ions for SIM detection and to develop novel and
      efficient reversed phase high performance liquid chromatographic (RP-HPLC)-UV
      Vis/ESI-MS method for the analysis of natural blue dyes. The procedure was
      successfully applied for identification of indigotin and carminic acid-main
      colorants extracted from a fiber taken from the blue-red 'Italian' tapestry (the
      collection of the National Museum in Warsaw, Poland).

PMID- 16575782
TI  - FT-ICRMS distinguishes the mechanism of the charge state reduction for multiply
      charged protein cations admixed with redox reagents in ESI.
AB  - Recently, we reported on a phenomenon in which multiply charged protein cations
      produced by electrospray ionization could be reduced to lower and narrower charge
      state distributions when admixed with reducing reagents 1,4-benzoquinone or
      quinhydrone. Circular dichroism spectra of the proteins indicated that secondary
      and tertiary structural changes upon addition of these reducing reagents were
      negligible, thus eliminating conformational effects as playing a role in the
      charge reduction mechanism. Furthermore, the extent of charge state reduction did
      not correspond with gas-phase basicities of the redox reagents, suggesting that
      solution-phase, and not gas-phase, behavior dominates the observed charge state
      reduction. The relatively low resolution of the triple quadrupole employed did
      not make it possible to distinguish isotopic distributions of the multiply
      charged cations in order to determine whether the observed phenomenon was the
      result of proton-transfer reactions between the multiply charged cations and the
      reducing reagent or because of electron transfer from the reducing reagent to the
      protein cations. Here, high-resolution ESI-Fourier transform ion cyclotron
      resonance mass spectrometry of several peptide amides in the presence of a redox
      reagent show isotopic distributions that are consistent only with the proton
      transfer mechanism.

PMID- 16575786
TI  - Close localization of DAP-kinase positive tumour-associated macrophages and
      apoptotic colorectal cancer cells.
AB  - The death-associated protein kinase (DAP-kinase) is a cytoskeleton-associated
      protein crucially involved in the induction of early apoptotic pathways. Aberrant
      hypermethylation of the DAP-kinase promoter plays a major role in tumorigenesis.
      We aimed to investigate the inactivation of DAP-kinase and its association with
      apoptotic cell death in 94 colorectal carcinomas. DAP-kinase promoter
      hypermethylation and mRNA expression were investigated using methylation-specific
      PCR and real-time RT-PCR, respectively. The expression of DAP-kinase, Fas, and
      Fas-ligand (FasL) proteins was studied by immunohistochemistry and
      immunofluorescence. Apoptosis of tumour cells was investigated using the TUNEL
      assay. DAP-kinase was expressed in tumour cells and tumour-invading macrophages
      and was closely associated with high numbers of apoptotic tumour cells. DAP
      kinase expression co-localized with FasL overexpression in tumour-associated
      macrophages, and aberrant promoter hypermethylation was verified in more than 50%
      of carcinomas. There was a tendency for proximal tumours to show DAP-kinase
      promoter methylation more frequently (p = 0.07). Promoter methylation resulted in
      a decrease or loss of DAP-kinase protein expression in tumour cells and tumour
      associated macrophages. Simultaneously, a decreased apoptotic count and loss of
      Fas/FasL expression was observed in tumour cells. Our study is the first to
      demonstrate DAP-kinase expression in invading tumour-associated macrophages in
      colorectal cancer. The presence of similar expression levels of DAP-kinase in
      tumour cells and associated macrophages, and their dependence on the promoter
      methylation status of the tumour cells, suggests cross talk between these cell
      types during apoptotic cell death.

PMID- 16575787
TI  - Principles of treatment for mentally disordered offenders.

PMID- 16575788
TI  - Women.

PMID- 16575789
TI  - Children and adolescents.

PMID- 16575790
TI  - Forensic issues in learning disability.

PMID- 16575791
TI  - Older people.

PMID- 16575792
TI  - A future in forensic psychiatry.

PMID- 16575793
TI  - Barriers to care in severe mental illness: accounts from perpetrators of intra
      familial homicide.
AB  - OBJECTIVE: To review perceptions of barriers to receiving effective mental health
      care described by patients who had committed intra-familial homicide in the
      context of untreated severe mental illness. METHOD: Semi-structured interviews
      addressed issues such as support, help-seeking, experience of illness, and what
      participants felt might have helped prevent the death(s). Transcripts were
      analysed for themes related to barriers to help-seeking. RESULTS: Themes
      identified included: hiding or minimizing difficulties, lack of knowledge or
      understanding of mental illness, loss of control in the context of illness,
      seduction by the illness, reality-distorting effects of the illness, distortion
      of interpersonal relationships, diminished ability to trust and difficulty
      acknowledging need for medication. CONCLUSIONS: Barriers to care exist at
      individual, interpersonal and wider societal levels and need to be addressed at
      all of them.

PMID- 16575794
TI  - Depression, hopelessness and suicide ideation among vulnerable prisoners.
AB  - BACKGROUND: Self-harm among prisoners is high, and suicide rates increasing.
      Assessment of depressive characteristics is easy. To what extent are these linked
      with previous self-harm? AIMS: To compare depressive characteristics of prisoners
      who report previous self-harm with those who do not. METHODS: Twenty-four new
      arrivals at an adult male category B local prison who reported previous episodes
      of suicidal behaviour (including self-harm and/or explicit attempted suicide)
      were assessed using the Beck Hopelessness Scale, the Beck Depression Inventory
      II, and the Beck Scale for Suicide Ideation. A further 24 new arrivals were
      matched as closely as possible with them on sociodemographic and offending
      characteristics. RESULTS: Mean scores on the Beck Hopelessness Scale, the Beck
      Depression Inventory-II, and the Beck Scale for Suicide Ideation were
      significantly higher among the prisoners with a history of self-harm. DISCUSSION:
      Prisoners with a previous history of self-harm are more likely than those without
      to show a range of depressive symptoms than their imprisoned peers without such a
      history, suggesting a continued vulnerability to self-harm and perhaps suicide.

PMID- 16575795
TI  - Changes in attitudes to personality disorder on a DSPD unit.
AB  - BACKGROUND: Psychiatric professionals tend to have poor attitudes towards people
      who suffer from personality disorder. Previous studies suggest that such
      attitudes are influenced by sufferer behaviours, organizational factors and the
      characteristics of individual professionals, but do similar considerations apply
      outside health services? AIM: To identify what events, experiences and factors in
      the course of daily work with personality-disordered people influence the
      attitudes and beliefs of prison staff. METHOD: Semi-structured interviews were
      conducted with prison officers working in a pilot "Dangerous and Severe
      Personality Disorder" Unit within a UK prison. Open questions were asked about
      any changes in their attitudes to or beliefs about personality-disordered
      inmates. RESULTS: Positive influences on attitude were: development of greater
      understanding of personality disorder and prisoners as individuals; improvement
      in inmate behaviours; education; the staff counselling programme; staff sharing
      support and skills; the challenge and purpose of the new role and having their
      views listened to. Negative influences were: delays in establishing the treatment
      programme; some inmate behaviours; fear and concern over their new roles and
      negative portrayal as a profession in the media. CONCLUSIONS: In order to
      maintain a high overall positive attitude among staff to working with people with
      personality disorder, units should have: consistency of direction and timely
      implementation of anticipated developments; clear philosophy and treatment
      regime; substantial investment in staff training programmes and effective
      programmes for the provision of clinical supervision to frontline staff.

PMID- 16575796
TI  - Service costs for severe personality disorder at a special hospital.
AB  - BACKGROUND: Much attention has been given to the reform of services for people
      with personality disorder in the UK, yet little is known of the cost of existing
      services, particularly in secure forensic settings. Existing cost estimates
      almost always rely on aggregate estimates of the cost of care rather than
      individual-level costing, but the latter is necessary for the economic evaluation
      of new services. METHOD: This paper uses a new instrument for recording service
      use in secure forensic settings to report the service use and care package costs
      of 16 patients being considered for the dangerous and severe personality disorder
      programme in the Personality Disorder Directorate at Rampton, a high secure
      hospital in Nottinghamshire, UK. RESULTS: The mean cost over a six-month period
      was 65,545 UK pounds (approximately 131,000 pounds per annum) but there was
      considerable variation within this figure, with a range of 59,119 to 82,709 UK
      pounds. CONCLUSIONS: Aggregate costs for individuals in secure hospital settings
      hide substantial variation between individuals. This paper demonstrates the
      feasibility of estimating the cost of individual care packages in a secure
      forensic setting.

PMID- 16575797
TI  - A form of relapse prevention for men in a high security hospital.
AB  - BACKGROUND: Marlatt and Gordon's relapse prevention model has evolved, and been
      applied to many repetitive problem behaviours, including drug use, gambling and
      sexual offending. High security hospital patients often present with a number of
      such behaviours. AIM: To evaluate a relapse prevention group in one high security
      hospital. METHOD: Nine patients were selected on clinical need for the group. In
      a naturalistic study design, each completed several self-report questionnaires
      pre- and post-group. RESULTS: Analysis of group results demonstrated a
      significant increase in guilt and acceptance of responsibility for offences (GBAI
      ratings), and reduced endorsement of pro-offending thinking styles (PICTS).
      Movement towards increased empathy, and decreased impulsivity and
      venturesomeness, did not reach significance. All participants showed some changes
      in desired directions but effects were small. CONCLUSIONS: Both relapse
      prevention and its evaluation are limited in high security hospitals by the
      restricted opportunities for testing out new skills. The feasibility of
      delivering an RP programme and evaluating it in high security has nevertheless
      been established. The small effects found may be promising, and suggest both
      justification and need for a randomized controlled trial of this approach in that
      setting.

PMID- 16575798
TI  - What can we learn from the oral intake of prions by sheep?
AB  - The central nervous system is the ultimate target of prions, the agents
      responsible for fatal neurodegenerative diseases known as transmissible
      spongiform encephalopathies (TSEs). The neuro-invasive phase and its related
      clinical signs take place after a long incubation period. During this
      asymptomatic phase, however, active transport and replication of the infectious
      agent take place in peripheral sites. The oral infection route has been
      extensively studied because of its implication in the recent epidemic of bovine
      spongiform encephalopathy (BSE) in cattle and of the resulting human cases of
      variant Creutzfeldt-Jakob disease (vCJD). Rodent models have been useful in
      studying some aspects of this pathogenesis. Now, new data on the initial steps of
      oral infection have been obtained in sheep. This species is naturally infected
      with scrapie by horizontal transmission and there is strong evidence implicating
      the oral route. Furthermore, the existence of resistant and susceptible genotypes
      offers the possibility of comparative studies. The data were obtained using
      surgical and biochemical procedures to modulate the efficiency of oral infection
      and show that, in sheep, the abnormal prion protein (PrP) associated with the
      infectious agent crosses the intact intestinal barrier at the level of the
      enterocytes and then passes rapidly into lymph. These steps are identical in
      susceptible and resistant sheep. Thereafter, replication takes place in lymphoid
      structures. Other results in the same study indicate that alimentary fluids
      almost completely degrade the PrP of the inoculum. Though not directly
      transposable to human diseases, in which it is not possible to study these early
      stages, these data allow the elaboration of a simplified concept for the
      pathogenesis of TSEs. They also suggest that human contamination at the level of
      the oral cavity might be more important than previously suspected.

PMID- 16575799
TI  - Transportation of prion protein across the intestinal mucosa of scrapie
      susceptible and scrapie-resistant sheep.
AB  - To determine the mechanisms of intestinal transport of infection, and early
      pathogenesis, of sheep scrapie, isolated gut-loops were inoculated to ensure that
      significant concentrations of scrapie agent would come into direct contact with
      the relevant ileal structures (epithelial, lymphoreticular, and nervous). Gut
      loops were inoculated with a scrapie brain pool homogenate or normal brain or
      sucrose solution. After surgery, animals were necropsied at time points ranging
      from 15 min to 1 month and at clinical end point. Inoculum-associated prion
      protein (PrP) was detected by immunohistochemistry in villous lacteals and in sub
      mucosal lymphatics from 15 min to 3.5 h post-challenge. It was also detected in
      association with dendritic-like cells in the draining lymph nodes at up to 24 h
      post-challenge. Replication of infection, as demonstrated by the accumulation of
      disease-associated forms of PrP in Peyer's patches, was detected at 30 days and
      sheep developed clinical signs of scrapie at 18-22 months post-challenge. These
      results indicate discrepancies between the routes of transportation of PrP from
      the inoculum and sites of de novo-generated disease-associated PrP subsequent to
      scrapie agent replication. When samples of homogenized inoculum were incubated
      with alimentary tract fluids in vitro, only trace amounts of protease-resistant
      PrP could be detected by western blotting, suggesting that the majority of both
      normal and abnormal PrP within the inoculum is readily digested by alimentary
      fluids.

PMID- 16575808
TI  - Introduction: what is forensic psychiatry?

PMID- 16575809
TI  - Do medical students need to know anything about forensic psychiatry?

PMID- 16575810
TI  - An introduction to law relevant to mentally disordered offenders.

PMID- 16575811
TI  - Specialist forensic mental health services.

PMID- 16575812
TI  - Prison psychiatry.

PMID- 16575813
TI  - Mental disorder and crime.

PMID- 16575814
TI  - How to assess and investigate a patient within a forensic psychiatry setting.

PMID- 16575818
TI  - How harmonized are we? Forensic mental health legislation and service provision
      in the European Union.

PMID- 16575820
TI  - Belgium and its internees: a problem for human rights and a stimulus for service
      change.

PMID- 16575832
TI  - Denaturing temperature selection may underestimate keratin mutation detection by
      DHPLC.
AB  - Keratins 8 and 18 (KRT8 and KRT18 genes; K8 and K18 proteins) variants are risk
      factors for developing end-stage liver disease and may be associated with
      inflammatory bowel disease and chronic pancreatitis. The frequency of K8/K18
      variants in American, British, German, and Italian populations differs. For
      example, one study showed no amino acid-altering K8/K18 mutations in 256 German
      patients with liver disorders, while another found 58 out of 467 American liver
      disease patients with K8/K18 mutations. Both studies used the WaveSystem, which
      utilizes DHPLC. We hypothesized that experimental conditions contribute to the
      discrepancy, and we tested this hypothesis using previously described K8/K18
      variants and a novel KRT18 c.1057C>G variant (K18 p.R353G) to optimize the DHPLC
      conditions in 10 examined exons under a range of denaturing temperatures. Six of
      16 tested variants in three of the 10 exons, including the frequent KRT8 c.184G>T
      (K8 p.G62C), KRT8 c.187A>G (K8 p.I63V), and KRT8 c.1022G>A (K8 p.R341H), could
      not be reliably detected when using temperatures suggested by the prediction
      software, but all these variants were readily detectable at 2 degrees C higher
      denaturing temperatures. Using optimized temperatures, we then tested available
      genomic DNA from 151 out of the 256 German liver disease patients for the
      presence of K8 variants in exons 1 and 6, where most of the American cohort K8
      variants occur. We identified 12 exonic and two intronic K8 variants: one KRT8
      c.184G>T (K8 p.G62C), two KRT8 c.187A>G (K8 p.I63V), seven KRT8 c.1022G>A (K8
      p.R341H), one KRT8 c.1128G>A (K8 p.E376E), two intronic KRT8 c.1202+46 A>T, and
      one hitherto undescribed KRT8 c.1138G>A (K8 p.V380I). Therefore, although DHPLC
      offers a robust and high throughput means for mutation analysis, assessment of
      denaturing temperature ranges, and possible inclusion of control mutants should
      be considered.

PMID- 16575833
TI  - Functional source separation from magnetoencephalographic signals.
AB  - We propose a novel cerebral source extraction method (functional source
      separation, FSS) starting from extra-cephalic magnetoencephalographic (MEG)
      signals in humans. It is obtained by adding a functional constraint to the cost
      function of a basic independent component analysis (ICA) model, defined according
      to the specific experiment under study, and removing the orthogonality
      constraint, (i.e., in a single-unit approach, skipping decorrelation of each new
      component from the subspace generated by the components already found). Source
      activity was obtained all along processing of a simple separate sensory
      stimulation of thumb, little finger, and median nerve. Being the sources obtained
      one by one in each stage applying different criteria, the a posteriori
      "interesting sources selection" step is avoided. The obtained solutions were in
      agreement with the homuncular organization in all subjects, neurophysiologically
      reacting properly and with negligible residual activity. On this basis, the
      separated sources were interpreted as satisfactorily describing highly
      superimposed and interconnected neural networks devoted to cortical finger
      representation. The proposed procedure significantly improves the quality of the
      extraction with respect to a standard BSS algorithm. Moreover, it is very
      flexible in including different functional constraints, providing a promising
      tool to identify neuronal networks in very general cerebral processing.

PMID- 16575834
TI  - European training in forensic psychiatry.

PMID- 16575835
TI  - The expanding phenotype of POMT1 mutations: from Walker-Warburg syndrome to
      congenital muscular dystrophy, microcephaly, and mental retardation.
AB  - The importance of O-glycosylation of alpha-dystroglycan (alpha-DG) is evident
      from the identification of POMT1 mutations in Walker-Warburg syndrome (WWS).
      Approximately one-fifth of the WWS patients show mutations in POMT1, which result
      in complete loss of protein mannosyltransferase activity. WWS patients are
      characterized by congenital muscular dystrophy (CMD) with severe brain and eye
      abnormalities. This suggests a crucial role for alpha-DG during development of
      these organs and tissues. Here we report new POMT1 mutations and polymorphisms in
      WWS patients. In addition, we report different compound heterozygous POMT1
      mutations in four unrelated families that result in a less severe phenotype than
      WWS, characterized by CMD with calf hypertrophy, microcephaly, and mental
      retardation. Compared to WWS patients, these patients have milder structural
      brain abnormalities, and eye abnormalities were absent, except for myopia in some
      cases. In these patients we postulate that one or both transcripts for POMT1
      confer residual protein O-mannosyltransferase activity. Our data suggest the
      existence of a disease spectrum of CMD including brain and eye abnormalities
      resulting from POMT1 mutations.

PMID- 16575837
TI  - Targeting the inflamed synovium: the quest for specificity.

PMID- 16575836
TI  - Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection
      rate.
AB  - Alagille syndrome (AGS) is caused by heterozygous mutations in JAG1, and
      mutations have been previously reported in about 70% of patients who meet
      clinical diagnostic criteria. We studied a cohort of 247 clinically well-defined
      patients, and using an aggressive and sequential screening approach we identified
      JAG1 mutations in 94% of individuals. Mutations were found in 232 out of 247
      patients studied and 83 of the mutations were novel. This increase in the
      mutation rate was accomplished by combining rigorous clinical phenotyping, with a
      combination of mutation detection techniques, including fluorescence in situ
      hybridization (FISH), genomic and cDNA sequencing, and quantitative PCR. This
      higher rate of mutation identification has implications for clinical practice,
      facilitating genetic counseling, prenatal diagnosis, and evaluation of living
      related liver transplant donors. Our results suggest that more aggressive
      screening may similarly increase the rate of mutation detection in other dominant
      and recessive disorders.

PMID- 16575838
TI  - Developmental and skill effects on the neural correlates of semantic processing
      to visually presented words.
AB  - Functional magnetic resonance imaging (fMRI) was used to explore the neural
      correlates of semantic judgments to visual words in a group of 9- to 15-year-old
      children. Subjects were asked to indicate if word pairs were related in meaning.
      Consistent with previous findings in adults, children showed activation in
      bilateral inferior frontal gyri (Brodmann area [BA] 47, 45) and left middle
      temporal gyrus (BA 21). Words with strong semantic association elicited
      significantly greater activation in bilateral inferior parietal lobules (BA 40),
      suggesting stronger integration of highly related semantic features. By contrast,
      words with weak semantic association elicited greater activation in left inferior
      frontal gyrus (BA 45) and middle temporal gyrus (BA 21), suggesting more
      difficult feature search and more extensive access to semantic representations.
      We also examined whether age and skill explained unique variance in the patterns
      of activation. Increasing age was correlated with greater activation in left
      middle temporal gyrus (BA 21) and inferior parietal lobule (BA 40), suggesting
      that older children have more elaborated semantic representations and more
      complete semantic integration processes, respectively. Decreasing age was
      correlated with activation in right superior temporal gyrus (BA 22) and
      decreasing accuracy was correlated with activation in right middle temporal gyrus
      (BA 21), suggesting the engagement of ancillary systems in the right hemisphere
      for younger and lower-skill children.

PMID- 16575840
TI  - Genetic variation in toll-like receptor 9 and susceptibility to systemic lupus
      erythematosus.
AB  - OBJECTIVE: Autoantibodies produced by differentiated B cells play an important
      role in the pathogenesis of systemic lupus erythematosus (SLE). The Toll-like
      receptor 9 (TLR-9) gene has recently emerged as an important costimulatory
      molecule for both B cells and dendritic cells that respond to chromatin immune
      complexes. Genetic variation affecting the function of TLR-9 may therefore
      increase or decrease the threshold of B cell or dendritic cell activation. This
      variability in activation threshold may, in turn, affect an individual's
      susceptibility to SLE. This study assessed the role of genetic variation within
      the TLR-9 gene in susceptibility to SLE. METHODS: We genotyped 362 SLE-affected
      subject/parent trios for 10 single-nucleotide polymorphisms (SNPs) covering a
      68,742-bp genomic segment that contains the TLR-9 gene and approximately 60 kb of
      flanking sequence. We analyzed the data using the transmission disequilibrium
      test. RESULTS: There was no association of susceptibility to SLE with any of the
      9 SNPs that generated usable data or the 8 haplotypes found at a frequency of
      >0.05 in this population. When analyzing the subset of 143 subjects with lupus
      nephritis, there was also no evidence of association between disease
      susceptibility and any SNP or haplotype. CONCLUSION: These results indicate that
      there is no evidence that common (frequency higher than 5%) alleles of the TLR-9
      gene contribute significantly to the genetic risk involved in susceptibility to
      SLE or lupus nephritis.

PMID- 16575841
TI  - A justification for using NMR model-free methods when investigating the solution
      structures of rhombic paramagnetic lanthanide complexes.
AB  - The detailed analysis of the 1H NMR hyperfine shifts according to the model-free
      methods shows that the semi-rigid monometallic complexes [Ln(L)(NO3)3] (Ln = Eu
      Yb) are isostructural in solution. The associated separation of contact and
      pseudo-contact contributions to the hyperfine NMR shifts in each rhombic
      lanthanide complex at room temperature provides paramagnetic susceptibility
      tensors whose principal magnetic axes match the expected symmetry requirements.
      Moreover, both axial (Delta chi(ax)) and rhombic (Delta chi(rh)) paramagnetic
      anisotropies display satisfactory linear dependence on Bleaney's factors, a
      correlation predicted by the approximate high-temperature expansion of the
      magnetic susceptibility limited to T(-2). Consequently, the simple, and
      chemically attracting NMR model-free methods are not limited to axial systems,
      and can be safely used for the investigation of the solution structures of any
      lanthanide complexes. Molecular-based structural criteria for the reliable
      estimation of paramagnetic susceptibility tensors by NMR are discussed, together
      with the assignment of the labels of the crystal-field and magnetic axes within
      Bleaney's approach.

PMID- 16575839
TI  - Identification and characterization of an Xp22.33;Yp11.2 translocation causing a
      triplication of several genes of the pseudoautosomal region 1 in an XX male
      patient with severe systemic lupus erythematosus.
AB  - The X;Y translocation break point sequence in an XX male patient with prepubertal
      systemic lupus erythematosus (SLE) was characterized with the intention of
      identifying a predisposing gene(s) for SLE. Spectral karyotyping of the patient's
      metaphase chromosomes showed normal autosomes and 2 X chromosomes, one of which
      displayed a small portion of the Y chromosome. Using a Y chromosome polymerase
      chain reaction (PCR) walking strategy and inverse PCR, we found that the abnormal
      recombination occurred between retroviral long terminal repeats located at
      Xp22.33 (position 0.95 Mb; inside the pseudoautosomal regions) and Yp11.2 (4.20
      Mb) downstream of the sex-determining region Y (SRY) gene. The complete DNA
      sequence of the break point was determined, revealing a partial duplication of
      the pseudoautosomal region 1 (PAR1) in the derivative X chromosome and causing a
      partial trisomy of the 12 known genes located between the interleukin-3 receptor
      alpha (IL3RA; position 1.1 Mb on the X and Y chromosomes) and CD99 (position 2.2
      Mb) genes inclusively. All other X chromosome genes were present as 2 copies.
      Real-time quantitative PCR confirmed the presence of 3 copies of each of the 12
      genes in the patient's genomic DNA. We also found that RNA for 1 of the candidate
      genes was indeed overexpressed in the patient's blood as compared with normal
      subjects. Taken together, the uniqueness of the translocation, the rarity of
      severe prepubertal SLE in males, and the presence of SLE in some patients with
      Klinefelter's syndrome (who have a triplication of the 2 PAR regions) point to a
      possible relationship between the partial triplication of the PAR1 region and the
      development of SLE.

PMID- 16575842
TI  - Court-mandated psychiatric outpatient treatment in New York: doesn't this process
      invoke more care than controversy?

PMID- 16575843
TI  - Mediator effects in the social development model: an examination of constituent
      theories.
AB  - BACKGROUND: The social development model (SDM) provides an explanatory framework
      for the progression of antisocial behaviour in children and adolescents. Although
      previous research has assessed the predictive validity of the model, alternative
      associations based on the SDM's constituent theories have not been examined.
      METHOD: Using structural equation modelling, a series of direct paths was
      examined for mediation by SDM constructs. Data for the study consisted of teacher
      , parent- and self-report of 1016 fourth- and fifth-grade students from the
      Raising Healthy Children project, a longitudinal etiological study with an
      embedded preventive intervention. RESULTS: Four of the seven paths examined were
      partially or totally mediated by SDM constructs. Specifically, the relationship
      between prosocial bonding and adolescent antisocial behaviour, as hypothesized by
      social control theory, was fully mediated by prosocial beliefs. As hypothesized
      by social learning theory, students' socioemotional and cognitive skills
      significantly predicted antisocial behaviour, independent of partial mediation
      through rewards, bonding and beliefs. As hypothesized by differential association
      theory, involvement with both prosocial and antisocial persons was directly
      associated with respective prosocial and antisocial beliefs, independent of
      partial mediation through rewards and bonding. CONCLUSIONS: These findings
      suggest additional associations that are not currently specified in the SDM and
      underscore the importance of re-examining hypotheses from constituent theories
      when integrating developmental models of antisocial behaviour.

PMID- 16575844
TI  - Impact of assertive community treatment and client characteristics on criminal
      justice outcomes in dual disorder homeless individuals.
AB  - BACKGROUND: People with severe mental illness and substance use disorders (dual
      disorder) often have considerable contact with the criminal justice system. AIMS:
      To test the effects of client characteristics on six criminal justice outcomes
      among homeless (at intake) people with mental illness and substance misuse
      disorders. METHODS: The sample was of participants in a randomized controlled
      trial comparing standard treatment, assertive community treatment (ACT) and
      integrated treatment (IT). Data were analysed using hierarchical logistic
      regression. RESULTS: Half the sample was arrested and a quarter incarcerated
      during the two-year follow-up period. The regression models explained between 22%
      and 35% of the variance of the following criminal justice measures: (1) major
      offences, (2) minor offences, (3) substance-use-related offences, (4)
      incarcerations, (5) arrests, and (6) summons. Prior criminal behaviour was the
      strongest predictor of all of the dependent variables; in general, demographic
      and diagnostic variables were not. Similarly, neither the type nor the amount of
      mental health treatment received predicted subsequent criminal behaviour.
      CONCLUSION: Elsewhere the authors have shown that ACT and IT had advantages for
      health and stability of accommodation but these analyses suggest that more
      specialized interventions are needed to reduce criminal behaviour in dual
      disorder individuals.

PMID- 16575845
TI  - Targeting of angiogenic endothelial cells at sites of inflammation by
      dexamethasone phosphate-containing RGD peptide liposomes inhibits experimental
      arthritis.
AB  - OBJECTIVE: To investigate whether RGD peptide-exposing long circulating
      polyethylene glycol (PEG) liposomes (RGD-PEG-L) targeted to alphavbeta3 integrins
      expressed on angiogenic vascular endothelial cells (VECs) are able to bind VECs
      at sites of inflammation and whether such liposomes containing dexamethasone
      phosphate (DEXP) can be used as carriers to interfere with the development of
      experimental arthritis. METHODS: Binding and internalization of RGD-PEG-L were
      studied by fluorescence-activated cell sorting and confocal microscopy using
      fluorescently labeled liposomes. Radiolabeled liposomes were used to test in vivo
      pharmacokinetics and inflammation site targeting in lipopolysaccharide (LPS)
      induced inflammation and adjuvant-induced arthritis (AIA) in rats. In vivo
      inflammation targeting was visualized by intravital microscopy using
      fluorescently labeled RGD-PEG-L. Therapeutic efficacy of DEXP-encapsulating RGD
      PEG-L compared with nontargeted liposomes was evaluated in rats with AIA.
      RESULTS: RGD-PEG-L bound to and were taken up by proliferating human VECs in
      vitro. In vivo, increased targeting of radiolabeled RGD-PEG-L to areas of LPS
      induced inflammation in rats was observed. Specific association with the blood
      vessel wall at the site of inflammation was confirmed by intravital microscopy.
      One single intravenous injection of DEXP encapsulated in RGD-PEG-L resulted in a
      strong and long-lasting antiarthritic effect in rat AIA. CONCLUSION: RGD-targeted
      PEG liposomes represent an endothelial cell-specific drug delivery system that
      targets VECs at sites of inflammation. Use of these liposomes to deliver DEXP to
      VECs at arthritis-affected sites proved efficacious in rat adjuvant arthritis.
      These data indicate that VECs have an essential role in the inflammation process
      and suggest the possibility of using VEC targeting for therapeutic intervention
      in inflammatory processes such as arthritis.

PMID- 16575847
TI  - Ethnicity and its relevance in a seven-year admission cohort to an English
      national adolescent medium secure health service unit.
AB  - BACKGROUND: There is some research which variously suggests that adults from some
      ethnic minority groups in the UK may be disproportionately likely to attract
      certain psychiatric diagnoses, and, in turn, to be admitted to inpatient
      facilities and compulsorily detained there; there are concerns too about over
      representation in the criminal justice system. Little such work has been done
      with adolescents. AIMS: To determine the proportion of young people from ethnic
      minorities admitted to one UK specialist medium secure hospital unit for
      adolescents and describe their diagnoses. METHODS: Data were extracted from the
      case records of all 61 young people admitted to this unit at any time between 1
      April 1995 and 31 March 2002. RESULTS: Inpatients from ethnic minority
      backgrounds were significantly over-represented when compared with National
      Census data. This was mainly accounted for by inpatients from Black African (11%)
      and Black Caribbean backgrounds (8%). There were, however, no within unit
      differences in final diagnoses between the ethnic groups. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: Our findings confirm both a high overall proportion of
      young people from ethnic minorities using a national medium secure hospital
      service and considerable ethnic diversity within that. They are discussed in the
      context of one relevant national government initiative for improving responses to
      minority groups.

PMID- 16575846
TI  - Cannabis dependence and mental health perception amongst people diverted by
      police after arrest for cannabis-related offending behaviour in Australia.
AB  - BACKGROUND: Use of cannabis and other mind-altering drugs may be associated with
      violence or other offending behaviours. In many countries mere possession of the
      drug may be sufficient to lead to a criminal conviction and, therefore, a
      criminal record. Recent legal and policy reforms in Australia have led to
      development of cannabis diversion programmes. OBJECTIVE: To describe substance
      misuse patterns and health perception in a consecutive series of young people in
      Queensland who were spared a criminal record because of a cannabis diversion
      scheme. METHOD: Between 9 July 2001 and 24 August 2004, 640 men and 187 women
      were diverted through the Queensland Illicit Drug Diversion Initiative (QIDDI)
      for treatment at a hospital alcohol and drug service. In this cross-sectional
      study of their drug use history, participants also completed the Severity of
      Dependence Scale (SDS) for cannabis and the General Health Questionnaire-28 (GHQ
      28). RESULTS: Almost 60% of participants were cannabis dependent (as determined
      by the SDS). Polysubstance use was also more prevalent amongst dependent
      participants. Self-reported health (GHQ-28) was poorer than expected from
      Australian normative data, and worse if participants were cannabis dependent.
      Applying the GHQ-28 threshold for psychiatric case identification (caseness),
      cannabis dependent participants had significantly higher level of caseness across
      all subscales of somatic concerns, anxiety, social dysfunction and depression.
      Dependent women registered the highest proportion of psychopathology,
      particularly anxiety and social dysfunction. CONCLUSIONS: Young cannabis users in
      Queensland who come into contact with the police are more likely than not to be
      dependent on the drug. Their high levels of psychopathology suggest that they are
      better placed in healthcare rather than the criminal justice system, and that
      appropriately responsive mental healthcare programmes are needed.

PMID- 16575848
TI  - How many factors are there on the PICTS?
AB  - INTRODUCTION: Several different factor models have been proposed for the
      Psychological Inventory of Criminal Thinking Styles (PICTS), an 80-item self
      report measure designed to assess thinking styles believed to maintain a criminal
      lifestyle. AIMS: To perform further tests on the factor structure with two new
      samples, and exploit their divergent characteristics to test for generalizability
      of the result. METHOD: A series of factor analyses were performed on the PICTS,
      completed by two groups of offenders: 519 male prisoners and 227 female
      prisoners, to determine whether a one-factor, two-factor, four-factor or eight
      factor model best fitted the data. RESULTS: The two-factor model was superior to
      the one-factor model, and the four- factor model was superior to both. An eight
      factor model, the factors being identical to the original eight PICTS thinking
      style scales (Mollification, Cutoff, Entitlement, Power Orientation,
      Sentimentality, Superoptimism, Cognitive Indolence, Discontinuity), achieved a
      significantly better fit than any of the other models in the male sample; the
      four and eight factor models were not significantly different among the women.
      DISCUSSION: Modest to moderate fit was attained with the two-, four- and eight
      factor models when the root mean square error of approximation (RMSEA) was
      utilized but not when the goodness-of-fit index (GFI) was applied. It is
      concluded that the factor structure of the PICTS consists of two primary or major
      factors (problem avoidance, self-assertion/deception) and two secondary or minor
      factors (interpersonal hostility, denial of harm). The four-factor model seems
      likely to be generalizable across divergent offender samples.

PMID- 16575849
TI  - The complex nature of the interaction between disease activity and therapy on the
      lipid profile in patients with pediatric systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the prevalence of lipid abnormalities at different times
      and to determine the influence of both the disease and corticosteroid therapy on
      lipid abnormalities in pediatric patients with systemic lupus erythematosus
      (SLE). METHODS: Lipid measurements were obtained in an inception cohort of 139
      pediatric patients with SLE (114 females). Fasting levels of total cholesterol,
      triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density
      lipoprotein (HDL) cholesterol in the SLE patients were compared with those in age
      and sex-matched control subjects. Disease activity levels and medication dosages
      were obtained at the time of lipid measurements. RESULTS: At the time of
      diagnosis, the mean levels of total cholesterol, LDL cholesterol, and
      triglycerides were highest, whereas the mean levels of HDL cholesterol were
      lowest. The percentage of patients with abnormal triglyceride values was highest
      at diagnosis, decreased at year 1, and then remained relatively constant
      thereafter. The mean total cholesterol and LDL cholesterol levels decreased at
      year 1 as compared with the time of diagnosis and then remained relatively
      constant. The lowest mean HDL cholesterol levels were found at the time of
      diagnosis, and these values rose with time. Comparison of lipid levels at
      different prednisone dosages and disease activity levels revealed that changes in
      triglyceride levels were mainly associated with changes in disease activity,
      changes in both total cholesterol and LDL cholesterol levels were associated with
      changes in the prednisone dosage and not disease activity, and low levels of HDL
      cholesterol were associated with active SLE, whereas the prednisone dosage was
      associated with increased levels of HDL cholesterol. CONCLUSION: Factors
      intrinsic to SLE appear to alter lipid levels. Control of SLE may be the most
      important factor in improving abnormal lipid profiles, and paradoxically,
      prednisone therapy may improve abnormal lipid levels.

PMID- 16575850
TI  - Connexin-36 gap junctions mediate electrical coupling between ventral tegmental
      area GABA neurons.
AB  - Communication between neurons in the mammalian brain is primarily through
      chemical synapses; however, evidence is accumulating in support of electrical
      synaptic transmission between some neuronal types in the mature nervous system.
      The authors have recently demonstrated that the gap junction (GJ) blocker
      quinidine suppresses stimulus-induced and dopamine-evoked coupling of gamma amino
      butyric acid (GABA) neurons in the ventral tegmental area (VTA) of mature rats
      (Stobbs et al., 2004). The aim of this study was to evaluate the role of connexin
      36 (Cx36) GJs in mediating electrical coupling between VTA GABA neurons in P50-80
      rats in vivo and P25-50 rats in vitro. Single stimulation of the internal capsule
      (IC) evoked VTA GABA neuron spike couplets in mature rats when activated
      antidromically, and multiple poststimulus spike discharges (PSDs) when activated
      with brief high-frequency stimulation of the IC (ICPSDs). The Cx36 GJ blocker
      mefloquine (30 mg/kg) suppressed VTA GABA neuron ICPSDs in mature freely behaving
      rats. VTA GABA neurons recorded via whole-cell patch clamp in the midbrain slice
      preparation of P25-50 rats showed robust expression of Cx36 transcripts when
      tested with single-cell quantitative reverse transcription polymerase chain
      reaction. In P50-80 rats, Cx36 protein immunoreactivity was evident in the VTA
      and surrounding structures. Dye-coupling between VTA neurons was observed
      following Neurobiotin labeling of VTA GABA neurons, as well as with the
      fluorochrome Alexa Fluor 488 using real-time video fluorescent microscopy. Thus,
      mature VTA GABA neurons appear to be connected by electrical synapses via Cx36
      GJs, whose coupling is enhanced by corticotegmental input and by dopamine.

PMID- 16575851
TI  - Self-modeling structure of evoked postsynaptic potentials.
AB  - With the simplicity of the synaptic structure and physiology at neuromuscular
      junctions (NMJs) of crayfish and the given transmitter being released in quantal
      packets, a detailed assessment in the fundamental processes of chemical synaptic
      transmission is possible. Since the quantal event is the basic element of
      transmission, we consider an approach to further understand the characteristics
      of quantal responses. In this study, we introduce a method for combining
      information across excitatory postsynaptic potentials (EPSPs) that are quantal in
      nature. The method is called self-modeling regression, known in the statistics
      literature as SEMOR. This method illustrates that the differing timing and
      heights of EPSPs can be described with four coefficients measuring affine (shift
      and scale) transformations of the x and y axes. We demonstrate that this
      relationship allows us to provide a unified schema for the many functionals
      currently used in the literature, such as peak amplitude, tau, latency, area
      under the curve, or decay time. Computer code in R is available on the internet
      to perform the analysis.

PMID- 16575852
TI  - Primary central nervous system vasculitis in children.
AB  - OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a severe and
      ill-defined neurologic disease. The goal of this study was to characterize the
      presenting features, treatment, and neurologic outcome of PACNS in children
      (cPACNS) and to define the predictors of disease progression in order to identify
      high-risk patients with cPACNS. METHODS: The cohort comprised consecutive
      patients diagnosed as having cPACNS based on clinical and vascular imaging
      findings, including identification of arterial stenosis on conventional
      angiography or magnetic resonance (MR) angiography. Disease progression was
      defined angiographically at >3 months after initial angiography. Clinical data
      obtained in prospectively collected standardized assessments and results of
      laboratory tests, including detection of cerebrospinal fluid abnormalities, were
      noted, and neuroimaging studies were reanalyzed. Predictors of progression were
      identified and tested in multivariate regression models. RESULTS: Sixty-two
      consecutive patients with cPACNS (38 male, 24 female, median age 7.2 years) were
      included. Two distinct subgroups were identified, those with progressive disease
      and those with nonprogressive disease. Progressive cPACNS was found in 20 of 62
      children and was predicted by a clinical presentation of neurocognitive
      dysfunction, multifocal parenchymal lesions on MR imaging, and evidence of distal
      stenoses on angiography. CONCLUSION: The spectrum of PACNS in children includes
      both progressive and nonprogressive forms. Characteristic features at diagnosis
      can be used to predict later progression, to identify a distinct high-risk cPACNS
      cohort, and to help guide selection of patients for immunosuppressive therapy.

PMID- 16575853
TI  - Dopamine D1 receptors have subcellular distributions conducive to interactions
      with prodynorphin in the rat nucleus accumbens shell.
AB  - Activation of dopamine (DA) D1 receptors (D1Rs) in the nucleus accumbens (Acb)
      markedly affects the levels of prodynorphin, the precursor of aversion-associated
      dynorphin peptides. The location of prodynorphin, specifically as related to the
      dopaminergic inputs and D1Rs in the Acb, is fundamental for establishing the
      physiologically relevant sites. To determine these sites, we examined the
      electron microscopic dual-immunolabeling of prodynorphin and D1R or tyrosine
      hydroxylase (TH), a marker of catecholamine terminals in the rat Acb shell. This
      subregion is targeted by mesolimbic dopaminergic inputs affecting reward-aversion
      responses and locomotor activity. Prodynorphin was prominently localized to large
      (100-200 nm) granular aggregates in somatodendritic and axonal profiles, some of
      which expressed dynorphin A/B. In somata and dendrites, prodynorphin was often
      found in punctate clusters in the cytoplasm. Of the total prodynorphin-labeled
      dendrites, approximately 63% expressed D1Rs, which were largely located on the
      plasma membranes. In comparison with dendrites, many more axon terminals
      contained prodynorphin, although only 15% of these terminals contained D1R
      labeling. Prodynorphin terminals formed symmetric synapses with D1R-labeled or
      unlabeled dendrites, and also apposed TH-containing axon terminals. Our results
      provide ultrastructural evidence that in the Acb shell, the prodynorphin is
      available for cleavage to physiologically active peptides in both dendrites and
      terminals of neurons that express D1Rs. They also indicate that dynorphin
      peptides have distributions that would enable their participation in modulation
      of DA release or D1R-mediated postsynaptic responses in Acb shell neurons.

PMID- 16575855
TI  - Inhibition of systemic sclerosis dermal fibroblast type I collagen production and
      gene expression by simvastatin.
AB  - OBJECTIVE: To examine whether statins are capable of modulating collagen gene
      expression in cultured systemic sclerosis dermal fibroblasts. METHODS: Cultured
      dermal fibroblasts from 3 patients with diffuse systemic sclerosis of recent
      onset were treated with 5 microM and 10 microM of simvastatin for 3 or 4 days.
      Morphologic features, cytotoxicity, and type I collagen production and messenger
      RNA (mRNA) levels in the fibroblasts were examined. The effects of mevalonate,
      geranylgeranyl pyrophosphate (GGPP), and farnesyl pyrophosphate (FPP), which are
      lipids downstream from the hydroxymethylglutaryl-coenzyme A block, were also
      examined. Transient transfections with COL1A1 promoter-reporter constructs and
      electrophoretic gel mobility shift assays were utilized to examine COL1A1
      transcription and Sp1 and CCAAT-box binding factor (CBF) binding. RESULTS:
      Simvastatin did not cause morphologic changes or cytotoxicity in the fibroblasts,
      even after 4 days of treatment. Type I collagen production and mRNA levels showed
      a potent and dose-related inhibition following 3 and 4 days of treatment. The
      inhibition of collagen gene expression by simvastatin was completely reversed by
      mevalonate and GGPP, but not by FPP. The statin effects occurred at the
      transcriptional level and involved the proximal COL1A1 promoter region
      encompassing -174 bp. A significant reduction in Sp1 and CBF binding activity was
      also found in simvastatin-treated cells. CONCLUSION: Simvastatin is a powerful
      inhibitor of type I collagen gene expression in normal and systemic sclerosis
      fibroblasts. The pleiotropic protective effects of statins on various endothelial
      and immune cell functions in conjunction with their potent inhibitory effects on
      type I collagen gene expression suggest that statins may be effective therapeutic
      agents in systemic sclerosis.

PMID- 16575856
TI  - Contribution of activin receptor-like kinase 5 (transforming growth factor beta
      receptor type I) signaling to the fibrotic phenotype of scleroderma fibroblasts.
AB  - OBJECTIVE: To use a specific transforming growth factor beta receptor type I
      (TGFbetaRI; activin receptor-like kinase 5 [ALK-5]) kinase inhibitor (SD208) to
      determine the role of activation of the TGFbetaRI kinase (ALK-5) in maintaining
      the profibrotic phenotype of dermal fibroblasts in systemic sclerosis (SSc).
      METHODS: The effect of SD208 on the expression of key biochemical markers of the
      fibrotic phenotype was compared in fibroblasts cultured from clinically involved
      (lesional) and clinically uninvolved skin of patients with diffuse cutaneous SSc
      (dcSSc) and in fibroblasts from healthy controls matched for age, sex, and
      anatomic site. Protein expression was compared together with the ability of
      fibroblasts to adhere to the extracellular matrix and to remodel and contract a
      free-floating fibroblast-populated type I collagen lattice. RESULTS: Inhibiting
      TGFbetaRI kinase reduced the expression of a cohort of fibrotic markers by dermal
      fibroblasts from patients with dcSSc, including type I collagen and beta1
      integrin. Moreover, inhibition also attenuated the elevated adhesive and
      contractile abilities of dcSSc fibroblasts. CONCLUSION: Our data suggest that
      some of the key profibrotic features of lesional SSc fibroblasts are dependent
      upon ALK-5 activity. Thus, TGFbetaRI kinase-mediated signaling may contribute to
      dermal fibrosis in dcSSc.

PMID- 16575857
TI  - Additional human beta2-microglobulin curbs HLA-B27 misfolding and promotes
      arthritis and spondylitis without colitis in male HLA-B27-transgenic rats.
AB  - OBJECTIVE: Ankylosing spondylitis and related spondylarthritides are associated
      with HLA-B27, and also with intestinal inflammation, by unknown mechanisms. The
      folded HLA-B27 molecule is a trimer of heavy chain, beta2-microglobulin (beta2m),
      and short peptide. However, B27 heavy chain has an unusual propensity to misfold
      and trigger the unfolded protein response (UPR). This study was initiated to test
      the hypothesis that B27 misfolding plays a role in the pathogenesis of
      spondylarthritis. METHODS: Rats with high transgene copy numbers of HLA-B27 heavy
      chain together with human beta2m (Hubeta2m) spontaneously develop colitis,
      peripheral arthritis, and occasional spondylitis, and those with lower transgene
      copy numbers remain healthy. We crossed disease-prone and healthy HLA
      B27/Hubeta2m-transgenic rat lines with a healthy line, 283-2, carrying only the
      Hubeta2m transgene. HLA-B27 assembly was assessed by pulse-chase analysis of B27
      molecules, and UPR triggering was assessed by measuring BiP/Grp78 messenger RNA
      (mRNA) in splenic concanavalin A blasts. Surface expression of B27 and Hubeta2m
      was determined by flow cytometry. Disease manifestations were identified by
      clinical observation, histology, and measurement of cytokine mRNA. RESULTS: The
      extra Hubeta2m from the 283-2 line significantly reduced B27 misfolding and UPR
      triggering. Unexpectedly, however, F1 male offspring of the healthy 21-3 line
      crossed with the 283-2 line showed a high prevalence, severity, and duration of
      arthritis and spondylitis, in the absence of colitis. The arthropathy showed many
      features characteristic of human spondylarthritis. CONCLUSION: These results
      suggest that B27 misfolding is associated with intestinal inflammation, but that
      neither B27 misfolding nor intestinal inflammation is critical to the development
      of B27-associated arthropathy.

PMID- 16575858
TI  - A high-resolution magnetic resonance imaging study of distal interphalangeal
      joint arthropathy in psoriatic arthritis and osteoarthritis: are they the same?
AB  - OBJECTIVE: Distal interphalangeal (DIP) joint arthropathy is characteristic of
      both psoriatic arthritis (PsA) and osteoarthritis (OA), but the microanatomic
      basis for DIP joint localization is poorly understood. This study used high
      resolution magnetic resonance imaging (MRI) to investigate the basis for hand
      disease localization in both conditions. METHODS: Twenty patients matched for
      disease duration (10 with DIP joint PsA and 10 with DIP joint OA) and 10 normal
      control subjects were scanned with a 1.5T MRI scanner utilizing a high-resolution
      23-mm diameter surface coil with displayed pixel dimensions of 80-100 mum. Images
      were obtained precontrast and postcontrast, and all joint structures, including
      ligaments, tendons, and entheses, were evaluated by 2 independent assessors.
      RESULTS: PsA could be distinguished from OA on the basis of more severe
      inflammation in the collateral ligaments and the extensor tendons and more severe
      changes at the corresponding DIP joint entheseal insertions. A much greater
      degree of extracapsular enhancement, with diffuse involvement of the nailbed and
      diffuse bone edema without cartilage damage, was also typical of PsA. Compared
      with the normal controls, the OA cohort exhibited prominent ligament and
      entheseal changes, but with much less contrast enhancement than in PsA and less
      bone involvement at the insertions. CONCLUSION: These findings suggest prominent
      inflammatory changes in ligament, tendon, enthesis, and adjacent bone in the DIP
      joint disease of PsA patients. Involvement of the same structures is common in
      the DIP joints of OA patients, but inflammatory changes are much less marked.
      These findings are potentially important for a better understanding of arthritis
      in humans.

PMID- 16575859
TI  - Acute heavy-resistance exercise-induced pain and neuromuscular fatigue in elderly
      women with fibromyalgia and in healthy controls: effects of strength training.
AB  - OBJECTIVE: To examine heavy-resistance exercise-induced acute neuromuscular
      fatigue, blood lactate concentration, and muscle pain in elderly women with
      fibromyalgia (FM) and in healthy controls before and after a period of strength
      training. METHODS: Thirteen elderly women with FM (mean+/-SD age 60+/-2 years)
      and 10 healthy women (mean+/-SD age 64+/-3 years) performed a heavy-resistance
      fatiguing protocol (5 sets of leg presses with 10 repetitions maximum) before and
      after a 21-week strength training period. Maximal isometric force and
      electromyography (EMG) activity of leg extensors and blood lactate concentration
      were measured during the loading. Pain was assessed by visual analog scale.
      RESULTS: The strength training led to large increases in maximal force and EMG
      activity of the muscles and contributed to the improvement in loading performance
      (average load/set) at week 21. The fatiguing loading sessions typically applied
      in strength training before and after the experimental period caused remarkable
      and comparable acute decreases in maximal force and increases in blood lactate
      concentration in both groups. Acute exercise-induced muscle pain increased
      similarly in both groups, and the pain level in women with FM was lowered after
      the 21-week training period. CONCLUSION: The increased strength in women with FM
      improved high-load performance and also seemed to attenuate perceived pain. Acute
      exercise-induced neuromuscular changes and the time course of muscle pain in
      women with FM were comparable with findings in healthy controls, which suggests a
      typical fatiguing process and a similar trainability of the muscles in elderly
      women with FM.

PMID- 16575860
TI  - Ectopic calcification among families in the Azores: clinical and radiologic
      manifestations in families with diffuse idiopathic skeletal hyperostosis and
      chondrocalcinosis.
AB  - OBJECTIVE: Twelve families that were multiply affected with diffuse idiopathic
      skeletal hyperostosis (DISH) and/or chondrocalcinosis, were identified on the
      island of Terceira, The Azores, potentially supporting the hypothesis that the 2
      disorders share common etiopathogenic factors. The present study was undertaken
      to investigate this hypothesis. METHODS: One hundred three individuals from 12
      unrelated families were assessed. Probands were identified from patients
      attending the Rheumatic Diseases Clinic, Hospital de Santo Espirito, in The
      Azores. Family members were assessed by rheumatologists and radiologists.
      Radiographs of all family members were obtained, including radiographs of the
      dorsolumbar spine, pelvis, knees, elbows, and wrists, and all cases were screened
      for known features of chondrocalcinosis. RESULTS: Ectopic calcifications were
      identified in 70 patients. The most frequent symptoms or findings were as
      follows: axial pain, elbow, knee and metacarpophalangeal (MCP) joint pain,
      swelling, and/or deformity, and radiographic enthesopathic changes. Elbow and MCP
      joint periarticular calcifications were observed in 35 and 5 patients,
      respectively, and chondrocalcinosis was identified in 12 patients. Fifteen
      patients had sacroiliac disease (ankylosis or sclerosis) on computed tomography
      scans. Fifty-two patients could be classified as having definite (17%), probable
      (26%), or possible (31%) DISH. Concomitant DISH and chondrocalcinosis was
      diagnosed in 12 patients. Pyrophosphate crystals were identified from knee
      effusions in 13 patients. The pattern of disease transmission was compatible with
      an autosomal-dominant monogenic disease. The mean age at which symptoms developed
      was 38 years. CONCLUSION: These families may represent a familial type of
      pyrophosphate arthropathy with a phenotype that includes peripheral and axial
      enthesopathic calcifications. The concurrence of DISH and chondrocalcinosis
      suggests a shared pathogenic mechanism in the 2 conditions.

PMID- 16575861
TI  - Quantitative fluorescence spectra and quantum yield map of synthetic pheomelanin.
AB  - Spectroscopic studies of pheomelanin and its constituents have been sparse. These
      data present what is by far the most complete description of the fluorescence
      characteristics of synthetic pheomelanin. Emission spectra between 260 and 600 nm
      were acquired for excitation wavelengths between 250 and 500 nm at 1-nm
      intervals. A quantum yield map is also presented, correcting the fluorescence
      intensities for differences in species concentration and molar absorptivity.
      These fluorescence features exhibit interesting similarities and differences to
      eumelanin, and these data are interpreted with respect to possible chemical
      structures. Overall, these data suggest that pheomelanin oligomers may be more
      tightly coupled than those of eumelanin. Finally, the quantum yield is shown to
      be on the order of 10(-4) and exhibit a complex dependence on excitation energy,
      varying by a factor of 4 across the energies employed here.

PMID- 16575862
TI  - Systemic sclerosis: brain abnormalities revealed by conventional magnetic
      resonance imaging and magnetization transfer imaging.

PMID- 16575863
TI  - Is atherosclerosis in rheumatoid arthritis related to disease severity and
      extraarticular manifestations? Comment on the article by Chung et al.

PMID- 16575865
TI  - The pros and cons of muscle co-contraction in osteoarthritis of the knee: comment
      on the article by Lewek et al.

PMID- 16575867
TI  - Aromatase inhibitors and osteoporosis: comment on the review by Felson and
      Cummings.

PMID- 16575870
TI  - Peripheral blood T lymphocytes from patients with early rheumatoid arthritis
      express RANKL and interleukin-15 on the cell surface and promote
      osteoclastogenesis in autologous monocytes.
AB  - OBJECTIVE: To investigate the osteoclastogenic potential of T cells from the
      peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid
      arthritis (RA) on autologous monocytes, and to study the cytokines implicated in
      this process. METHODS: T cells and monocytes were isolated from the PB of 20
      healthy subjects and 20 patients with early RA, and from the SF of 20 patients
      with established RA. Autologous T cell/monocyte cocultures were established in
      the absence of exogenous cytokines or growth factors in order to examine
      spontaneous ex vivo osteoclast differentiation by tartrate-resistant acid
      phosphatase staining and calcified matrix resorption activity. RESULTS: Surface
      RANKL was expressed on freshly isolated T cells from the PB of patients with
      early RA and the SF of patients with established RA. In addition, surface
      interleukin-15 (IL-15) was detected on freshly isolated T cells and monocytes
      from the PB of patients with early RA and the SF of patients with established RA.
      Autologous T cell/monocyte cocultures derived from the SF of patients with
      established RA and from the PB of patients with early RA, but not from the PB of
      healthy controls, resulted in osteoclast differentiation that was significantly
      inhibited by osteoprotegerin (OPG) and by neutralizing monoclonal antibodies to
      IL-15, IL-17, tumor necrosis factor alpha (TNFalpha), and IL-1beta. OPG, anti
      TNFalpha, and anti-IL-1beta demonstrated a cooperative inhibitory effect. At 1
      year followup, surface RANKL and IL-15 and ex vivo osteoclastogenesis were no
      longer observed on PB T cells or monocytes from patients with early RA in whom
      clinical remission had been achieved with treatment. CONCLUSION: T cells are
      important contributors to the pathogenesis of bone erosions in RA through
      interaction with osteoclast precursors of the monocyte/macrophage lineage.

PMID- 16575871
TI  - Antagonist of interferon-inducible protein 10/CXCL10 ameliorates the progression
      of autoimmune sialadenitis in MRL/lpr mice.
AB  - OBJECTIVE: Mononuclear cell infiltration of the salivary glands is a major
      feature of Sjogren's syndrome (SS) and its animal model. Local generation of
      chemokines and the presence of chemokine receptors on the infiltrating cells may
      be involved in this process. We undertook the present study to investigate the
      expression of chemokines during the development of autoimmune sialadenitis in
      MRL/lpr mice and the therapeutic effect of chemokine antagonists on sialadenitis.
      METHODS: NH2-terminal-truncated interferon-inducible protein 10 (IP-10)/CXCL10
      analogs were transfected into a nonmetastatic fibroblastoid cell line, MRL/N-1,
      and injected subcutaneously into MRL/lpr mice, and the effects on sialadenitis
      were monitored. RESULTS: IP-10 analogs truncated by 5 or more amino acid residues
      from the N-terminal failed to induce chemotaxis and calcium influx by CXCR3
      expressing cells. Of these, the most potent antagonist (AT) (IP-10-AT) was a
      molecule with methionine added after removal of the 5 N-terminal amino acid
      residues. Significantly increased expression of the Th1-associated chemokines IP
      10, monokine induced by interferon-gamma/CXCL9, and interferon-inducible T cell
      chemoattractant/CXCL11 was induced in the ductal epithelium by interferon-gamma
      produced in the salivary glands, whereas expression of the Th2-associated
      chemokines thymus and activation-regulated chemokine (TARC)/CCL17 and monocyte
      derived chemokine/CCL22 was almost undetectable during sialadenitis. Inoculation
      of IP-10-AT into MRL/lpr mice during the early stage of sialadenitis
      significantly reduced periductal mononuclear cell infiltration and parenchymal
      destruction compared with these features in control and TARC-AT-bearing mice.
      This was due to a significant reduction in infiltration of CXCR3+ T cells,
      predominantly Th1 cells, resulting in decreased interferon-gamma production.
      CONCLUSION: We prepared a novel potent IP-10 antagonist and demonstrated its
      ability to ameliorate the progression of autoimmune sialadenitis. This agent may
      provide a new therapeutic approach to SS.

PMID- 16575872
TI  - Target genes of the WNT/beta-catenin pathway in Wilms tumors.
AB  - The WNT/beta-catenin pathway is involved in numerous human cancers. Mutations of
      the CTNNB1 (beta-catenin) gene have also been detected in a subset of pediatric
      Wilms tumors, but the target genes of the deregulated WNT/beta-catenin pathway in
      these tumors have yet to be identified. To compare gene expression profiles of
      Wilms tumors with and without mutations of CTNNB1, we used 11.5-k cDNA
      microarrays. Most of the tumors (86%) had received preoperative chemotherapy as
      mandated by the European SIOP protocol. The comparison between Wilms tumors with
      and without CTNNB1 mutations revealed several target genes specifically
      deregulated in CTNNB1-mutated Wilms tumors. Among these, PITX2, APCDD1, and two
      members of the endothelin axis (EDN3 and EDNRA) are directly activated downstream
      targets of the WNT/beta-catenin pathway that may enhance proliferation of these
      tumor cells. In addition, several upstream inhibitors of WNT/beta-catenin
      signaling like WIF1 and PRDC were also strongly up-regulated in the CTNNB1
      mutated Wilms tumors. This overexpression may be a negative feedback mechanism in
      tumors with uncontrolled WNT signaling. Moreover, we identified deregulated genes
      in both the retinoic acid and the RAS pathways, such as ATX/ENPP2 and RIS1,
      suggesting an association between these two pathways with that of WNT. In
      addition, the strong representation of muscle-related genes in the expression
      profile of CTNNB1-mutated Wilms tumors corresponded to histologically detectable
      areas of myomatous cells in these tumors that displayed intense and preferential
      nuclear beta-catenin antibody staining. This article contains Supplementary
      Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

PMID- 16575873
TI  - Drug-excipient interactions in ketoprofen: a vibrational spectroscopy study.
AB  - Ketoprofen (3-benzoyl-alpha-methylbenzeneacetic acid) is a widely used
      nonsteroidal anti-inflammatory drug (NSAID), always administered in the form of
      drug-excipient physical mixtures (PMs). The occurrence of possible interactions
      between ketoprofen and two commonly used excipients-lactose (LAC) and
      polyvinylpyrrolidone (PVP)-was evaluated, through vibrational spectroscopy
      techniques [both Raman and Inelastic Neutron Scattering (INS)]. Spectral evidence
      of drug:excipient close contacts, which were enhanced by aging, was verified for
      the (1:1) (w:w) (ketoprofen:PVP) and (ketoprofen:LAC) PMs, both by Raman and INS.
      These interactions were found to involve mainly the central carbonyl and the
      terminal methyl-carboxylic moieties of the ketoprofen molecule, this being
      reflected in particular vibrational modes, such as the methyl torsion, the out-of
      plane C-OH bending, and the inter-ring C=O stretching.

PMID- 16575874
TI  - The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is
      amplified in late-stage prostate cancer.
AB  - Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2)
      has been found in several malignancies, including prostate cancer, with an
      aggressive phenotype. Amplification of the gene has previously been demonstrated
      in several malignancies, but not in prostate cancer. Our goal was to evaluate the
      gene copy number and expression alterations of EZH2 in prostate cancer. The copy
      number of EZH2 in cell lines (LNCaP, DU145, PC-3, 22Rv1), xenografts (n = 10),
      and clinical tumors (n = 191) was studied with fluorescence in situ
      hybridization. All cell lines had a gain of EZH2. Eight of the ten xenografts
      showed an increased copy number of the gene, including one case of high-level
      amplification (>or=5 copies of the gene and EZH2/centromere ratio >or=2). 34/125
      (27%) of untreated prostate carcinomas showed increased copy number, but only one
      case of low-level amplification (>or=5 copies of the gene and EZH2/centromere
      ratio <2), whereas half (25/46) of the hormone-refractory carcinomas showed
      increased copy number, including seven cases of low-level amplification and three
      cases of high-level amplification (P < 0.0001). Expression of EZH2 was
      significantly (P = 0.0009) higher in hormone-refractory prostate cancer compared
      with that in benign prostatic hyperplasia or untreated cancer, according to
      quantitative real-time RT-PCR assay. Also, the expression of EZH2 protein was
      found to be higher in hormone-refractory tumors than in hormone-naive tumors by
      immunohistochemistry. The EZH2 gene amplification was significantly (P < 0.05)
      associated with increased EZH2 protein expression. The data show that
      amplification of the EZH2 gene is rare in early prostate cancer, whereas a
      fraction of late-stage tumors contains the gene amplification leading to the
      overexpression of the gene, thus indicating the importance of EZH2 in the
      progression of prostate cancer.

PMID- 16575875
TI  - Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate
      cancer.

PMID- 16575878
TI  - On the determination of empirical absolute chiral structure: chiroptical spectrum
      correlations for D3 lanthanide (III) complexes.
AB  - Circularly polarized luminescence (CPL) from selected transitions of Eu(III) in
      resolved single crystals of Na3[Eu(ODA)3].2NaClO4.6H2O are compared to CPL
      results obtained from solutions containing perturbed racemic mixtures of Eu(2,6
      pyridine-dicarboxylate)3 (3-) and enantiomerically pure d-f helicate LambdaLambda
      (-)EuCr(L8)3] in order to determine an empirical relationship between helicity
      and CPL spectra. Comparison of the CPL results, even for the magnetic dipole
      allowed transitions of Eu(III) where one measures large chiral discrimination,
      shows that the signs and magnitudes do not correlate with the overall helicity of
      the Eu(III) site. It is concluded that the symmetry of the Eu(III) site in
      LambdaLambda-(-)EuCr(L8)3 is not close enough to D3 to allow for the confirmation
      of the presumed spectra:structure correlation.

PMID- 16575876
TI  - A genome wide linkage search for breast cancer susceptibility genes.
AB  - Mutations in known breast cancer susceptibility genes account for a minority of
      the familial aggregation of the disease. To search for further breast cancer
      susceptibility genes, we performed a combined analysis of four genome-wide
      linkage screens, which included a total of 149 multiple case breast cancer
      families. All families included at least three cases of breast cancer diagnosed
      below age 60 years, at least one of whom had been tested and found not to carry a
      BRCA1 or BRCA2 mutation. Evidence for linkage was assessed using parametric
      linkage analysis, assuming both a dominant and a recessive mode of inheritance,
      and using nonparametric methods. The highest LOD score obtained in any analysis
      of the combined data was 1.80 under the dominant model, in a region on chromosome
      4 close to marker D4S392. Three further LOD scores over 1 were identified in the
      parametric analyses and two in the nonparametric analyses. A maximum LOD score of
      2.40 was found on chromosome arm 2p in families with four or more cases of breast
      cancer diagnosed below age 50 years. The number of linkage peaks did not differ
      from the number expected by chance. These results suggest regions that may harbor
      novel breast cancer susceptibility genes. They also indicate that no single gene
      is likely to account for a large fraction of the familial aggregation of breast
      cancer that is not due to mutations in BRCA1 or BRCA2.

PMID- 16575877
TI  - Microarray-based survey of CpG islands identifies concurrent hyper- and
      hypomethylation patterns in tissues derived from patients with breast cancer.
AB  - Maintenance of CpG island methylation in the genome is crucial for cellular
      homeostasis and this balance is disrupted in cancer. Our rationale was to compare
      the methylation of CpG islands in tissues (tumor, healthy breast and blood) from
      patients with breast cancer. We studied 72 genes in 103 samples using microarray
      hybridization and bisulfite sequencing. We observed tumor specific hyper- or
      hypomethylation of five genes; COL9A1, MT1A, MT1J, HOXA5 and FLJ45983. A general
      drop of methylation in COL9A1 was apparent in tumors, when compared with blood
      and healthy breast tissue. Furthermore, one tumor displayed a complete loss of
      methylation of all five genes, suggesting overall impairment of methylation. The
      downstream, evolutionary conserved island of HOXA5 showed hypomethylation in 18
      tumors and complete methylation in others. This CpG island also displayed a
      semimethylated state in the majority of normal breast samples, when compared to
      complete methylation in blood. Distinct methylation patterns were further seen in
      MT1J and MT1A, belonging to the metallothionein gene family. The CpG islands of
      these genes are spaced by 2 kb, which shows selective methylation of two
      structurally and functionally related genes. The promoters of FLJ45983 and MT1A
      were methylated above 25% in 18 primary and metastatic tumors. Concurrently,
      there was also >10% methylation of healthy breast tissue in 11 and 5 samples,
      respectively. This suggests that the methylation process for the latter two genes
      takes place already in normal breast cells. Our results also point to a
      considerable heterogeneity of epigenetic disturbance in breast cancer. This
      article contains Supplementary Material available at
      http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

PMID- 16575879
TI  - Enantioselective metabolism of ifosfamide by the kidney.
AB  - Ifosfamide (IF), a potent chemotherapeutic agent for solid tumors, is known to
      cause high rates of nephrotoxicity, which is most likely due to the renal
      production of the metabolite chloroacetaldehyde. Enantioselective oxidation of IF
      has been shown in the liver but has never been reported in the kidney. Using
      porcine and human kidney samples, as well as the renal porcine cell line LLCPK-1,
      we document enantioselective metabolism of IF with prevalent production of the N
      dechloroethylifosfamide (DCEIF) metabolites from the (S)-IF enantiomer compared
      to the amount of N-DCEIF metabolites produced from the (R)-IF enantiomers. Since
      IF enantiomers appear to be equally effective in chemotherapy, these results
      suggest that replacing the clinically standard racemic mixture of IF with (R)-IF
      may decrease renal metabolism of the drug and hence may decrease nephrotoxicity.

PMID- 16575880
TI  - Photo-ionization spectroscopy and mass spectrometry of some molecular and
      supramolecular asymmetric systems in the isolated state.
AB  - Asymmetric molecular and supramolecular systems are characterized by: i. the
      circular dicroism in the angular distribution of valence photoelectrons emitted
      from randomly oriented chiral molecules by their interaction with circularly
      polarized VUV light; ii. the different stability and reactivity of diastereomeric
      aggregates. Both these aspects may have some relationship with the "chiral
      enrichment mechanism" of chirogenesis, based on the preferential destruction of
      one enantiomer of a racemate by interaction with a chiral agent, whether a
      massive species or a circularly polarized photon. The most recent spectroscopic
      and mass spectrometric studies on this topic are reported in the present mini
      review.

PMID- 16575881
TI  - Effects of ssDNA sequences on non-sequence-specific protein binding.
AB  - The circular dichroism (CD) spectra of single-stranded DNAs (ssDNAs) are
      significantly perturbed by the binding of single-stranded DNA binding proteins
      such as the Ff bacteriophage gene 5 protein (g5p) and the A domain of the 70 kDa
      subunit of human replication protein A (RPA70-A). These two proteins have similar
      OB-fold secondary structures, although their CD spectra at wavelengths below 250
      nm differ greatly. The spectrum of g5p is dominated by a tyrosyl L(a) band at 229
      nm, while that of RPA70-A is dominated by its beta secondary structure. Despite
      differences in their inherent spectral properties, these two proteins similarly
      perturb the spectra of bound nucleic acid oligomers. CD spectra of free, non
      protein-bound ssDNAs are dependent on interactions of the nearest-neighboring
      nucleotides in the sequence. The CD spectra (per mol of nucleotide) of simple
      repetitive sequences 48 nucleotides in length and containing simple combinations
      of A and C are related by nearest-neighbor equations. For example, 3 x
      Deltaepsilon[d(AAC)(16)] = 3 x Deltaepsilon[d(ACC)(16)] + Deltaepsilon[d(A)(48)] 
      Deltaepsilon[d(C)(48)]. Moreover, nearest-neighbor equations relate the spectra
      of ssDNAs when they are bound by g5p, indicating that each type of perturbed
      nearest neighbor has a similar average structure within the binding site of the
      protein.

PMID- 16575883
TI  - 22q11.2 deletion mosaicism in patients with conotruncal heart defects.
AB  - BACKGROUND: Some patients with conotruncal heart defects (CTDs) have a chromosome
      22q11.2 deletion, but we do not know whether patients with CTDs who are missing
      the peripheral blood-cell chromosome 22q11.2 deletion are also missing the
      22q11.2 deletion in myocardial cells, and whether patients with the 22q11.2
      deletion can show a different 22q11.2 deletion in peripheral blood cells and
      myocardial cells due to a postzygotic mutation during the embryonic period.
      METHODS: A total of 32 Chinese pediatric nonsyndromic CTD patients (21 with
      tetralogy of fallot [TOF], 9 with double outlet right ventricle [DORV], 1 with
      pulmonary artery atresia with ventricular septal defect [PAA/VSD], and 1 with
      congenitally corrected transposition of the great arteries [CCTGA]), 12 females
      and 20 males ranging in age from 5 months to 7 years, were included in our study.
      We used fluorescence in situ hybridization (FISH) to find the chromosome 22q11.2
      deletion in peripheral blood cells and compared genotypes of 15 short tandem
      repeat (STR) markers within 22q11.2 between peripheral blood cells and myocardial
      cells to search for genetic mosaicism of the chromosome 22q11.2 deletion.
      RESULTS: Three patients, 2 with TOF and 1 with DORV, were determined to have the
      peripheral blood cell chromosome 22q11.2 deletion. There was no STR genotypic
      difference observed between peripheral blood cells and myocardial cells in
      patients with or without the chromosome 22q11.2 deletion. CONCLUSIONS: Genetic
      mosaicism may not play a major role in the etiology of isolated CTDs.

PMID- 16575882
TI  - Neural tube defects and maternal biomarkers of folate, homocysteine, and
      glutathione metabolism.
AB  - BACKGROUND: Alterations in maternal folate and homocysteine metabolism are
      associated with neural tube defects (NTDs). The role played by specific
      micronutrients and metabolites in the causal pathway leading to NTDs is not fully
      understood. METHODS: We conducted a case-control study to investigate the
      association between NTDs and maternal alterations in plasma micronutrients and
      metabolites in two metabolic pathways: methionine remethylation and glutathione
      transsulfuration. Biomarkers were measured in a population-based sample of women
      who had NTD-affected pregnancies (n = 43) and a control group of women who had a
      pregnancy unaffected by a birth defect (n = 160). We compared plasma
      concentrations of folate, vitamin B(12), vitamin B(6), methionine, S
      adenosylmethionine (SAM), s-adenosylhomocysteine (SAH), adenosine, homocysteine,
      cysteine, and reduced and oxidized glutathione between cases and controls after
      adjusting for lifestyle and sociodemographic factors. RESULTS: Women with NTD
      affected pregnancies had significantly higher plasma concentrations of SAH (29.12
      vs. 23.13 nmol/liter, P = .0011), adenosine (0.323 vs. 0.255 mumol/liter; P =
      .0269), homocysteine (9.40 vs. 7.56 micromol/liter; P < .001), and oxidized
      glutathione (0.379 vs. 0.262 micromol/liter; P = .0001), but lower plasma SAM
      concentrations (78.99 vs. 83.16 nmol/liter; P = .0172) than controls. This
      metabolic profile is consistent with reduced methylation capacity and increased
      oxidative stress in women with affected pregnancies. CONCLUSIONS: Increased
      maternal oxidative stress and decreased methylation capacity may contribute to
      the occurrence of NTDs. Further analysis of relevant genetic and environmental
      factors is required to define the basis for these observed alterations.

PMID- 16575884
TI  - Intrauterine growth restriction in like-sex twins discordant for structural
      defects.
AB  - BACKGROUND: An increased risk for intrauterine growth restriction in the affected
      member of like-sex twin pairs discordant for hypospadias has been reported. The
      purpose of this study was to document patterns of birth weight disparities in
      like-sex twins discordant for a variety of structural defects in order to
      determine if this is a general phenomenon seen in twins who are discordant for
      any malformation, is seen only in pairs discordant for certain specific
      malformations, or is unique to hypospadias. METHODS: Data were extracted from the
      Latin American Collaborative Study of Congenital Malformations (ECLAMC). Between
      1967 and 1999, all like-sex twin pairs discordant for hypospadias or any other
      isolated defect that met the criteria of at least 5 discordant pairs for which
      birth weight was available on both twins were selected. All nonmalformed like-sex
      twin pairs in the ECLAMC data base collected over the same study years were
      selected as controls. RESULTS: A total of 216 discordant malformed like-sex twin
      pairs in 13 defect categories and 328 nonmalformed like-sex twin pairs met the
      criteria for inclusion. The proportion of affected infants who were > or =20%
      smaller than their co-twin was statistically significantly different from
      controls for hypospadias, heart defects, anencephaly, and esophageal atresia.
      CONCLUSIONS: Intrauterine growth restriction seen in the affected member of like
      sex twin pairs discordant for hypospadias is not unique, but occurs as well in at
      least 3 additional structural malformations.

PMID- 16575885
TI  - Temporal control of gene recombination in astrocytes by transgenic expression of
      the tamoxifen-inducible DNA recombinase variant CreERT2.
AB  - Inducible gene modification using the Cre/loxP system provides a valuable tool
      for the analysis of gene function in the active animal. GFAP-Cre transgenic mice
      have been developed to achieve gene recombination in astrocytes, the most
      abundant cells of the central nervous system, with pivotal roles during brain
      function and pathology. Unfortunately, these mice displayed neuronal
      recombination as well, since the GFAP promoter is also active in embryonic radial
      glia, which possess a substantial neurogenic potential. To enable the temporal
      control of gene deletions in astrocytes only, we generated a transgenic mouse
      with expression of CreERT2, a fusion protein of the DNA recombinase Cre and a
      mutated ligand-binding domain of the estrogen receptor, under the control of the
      human GFAP promoter. In offspring originating from crossbreedings of GFAP-CreERT2
      transgenic mice with various Cre-sensitive reporter mice, consecutive
      intraperitoneal injections of tamoxifen induced genomic recombination selectively
      in astrocytes of almost all brain regions. In Bergmann glia, which represent the
      main astroglial cell population of the cerebellum, virtually all cells showed
      successful gene recombination. When adult mice received cortical stab wound
      lesions, simultaneously given tamoxifen induced substantial recombination in
      reactive glia adjacent to the site of injury. These transgenic GFAP-CreERT2 mice
      will allow the functional analysis of loxP-modified genes in astroglia of the
      postnatal and adult brain.

PMID- 16575886
TI  - Dominant-negative beta1 integrin mice have region-specific myelin defects
      accompanied by alterations in MAPK activity.
AB  - Recent studies have demonstrated the importance of beta1 integrin in
      oligodendrocyte maturation in vitro. Similar studies in vivo have been difficult
      due to the embryonic and perinatal lethality of null mutations in integrin
      subunits. Here, we have generated transgenic mouse models that overexpress full
      length beta1 integrin or express a dominant-negative beta1 integrin DeltaC
      (lacking the C-terminal tail) under the control of the proteolipid protein (PLP)
      promoter. We demonstrate that these transgenes are expressed predominantly in CNS
      tissues and more specifically in oligodendrocytes. Further analysis reveals that
      the dominant-negative beta1 integrin DeltaC transgenic mice, but not the full
      length beta1 integrin mice, have hypomyelinated axons in spinal cords and optic
      nerves. In addition, there is a significant increase in the number of
      unmyelinated axons within the spinal cords and optic nerves of the beta1 integrin
      DeltaC mice. In contrast, the corpus callosum from these mice did not show
      similar myelin defects. To assess if remyelination would be affected in the
      corpus callosum, mice were subjected to a cuprizone-induced demyelination.
      Interestingly, the dominant-negative mice recovered from this insult in a manner
      similar to the wild type littermates. Axons within the corpus callosum that were
      remyelinated had normal g-ratios; however, the actual percentage of myelinated
      axons was significantly reduced compared with wild type mice. We also show that
      the defects observed in the dominant-negative beta1 integrin DeltaC mice are
      accompanied by disruption of the MAP-kinase signaling pathway. Our work
      highlights the importance of beta1 integrin-mediated signaling in CNS myelination
      in vivo.

PMID- 16575888
TI  - Prenatal diagnosis of hypochondroplasia: report of two cases.
AB  - Hypochondroplasia (HCH) is an autosomal dominant skeletal dysplasia characterized
      by short extremities, short stature and lumbar lordosis, usually exhibiting a
      phenotype similar to but milder than achondroplasia (ACH). Mutations in the
      fibroblast growth factor receptor 3 (FGFR3) gene are present in a significant
      proportion of HCH patients. Reports of prenatal diagnosis of HCH are very rare
      and the phenotype/genotype correlation in these patients is poor. Here we present
      two sporadic cases with second trimester ultrasound findings consistent with a
      diagnosis of a non-lethal skeletal dysplasia. Ultrasound evaluation after 23
      weeks of gestation showed a decreased rate of development of the femora (femur
      length <fifth centile), while biparietal diameter, abdominal circumference, and
      foot length were within normal limits. Femur length/foot and femur
      length/abdominal circumference ratios were <0.87 and <0.18, respectively.
      Prenatal cytogenetic and molecular genetic analysis was performed. Karyotype was
      normal and FGFR3 G380R mutation characteristic of ACH was excluded in both
      fetuses. Molecular genetic analysis carried out retrospectively revealed that
      both fetuses were heterozygous for the C1620A mutation resulting in N540K
      substitution in FGFR3, the most common mutation in HCH. We conclude that the
      combination of ultrasound and molecular genetic approach is helpful for
      establishing an accurate diagnosis of HCH in utero and subsequently for
      appropriate genetic counseling and perinatal management.

PMID- 16575887
TI  - Aplasia and duplication of the thumb and facial clefts associated with fetal
      trisomy 18.

PMID- 16575890
TI  - Can we exclude the TXNIP gene as a candidate gene for familial combined
      hyperlipidemia?

PMID- 16575889
TI  - Behavioral and temperamental features of children with Costello syndrome.
AB  - Costello syndrome (CS) is a rare genetic condition due to germline mutations in
      HRAS proto-oncogene and characterized by increased birth weight, postnatal growth
      retardation, distinctive facial appearance, typical medical problems (including
      feeding problems in the neonatal period), cutaneous anomalies, and developmental
      delay. Outgoing personality has often been noted in case reports, but few studies
      have focused specifically on the behavioral aspects of CS. A preliminary survey
      described irritability in younger patients with improvement between age 2 and 4,
      but a standardized psychometric tool was not used. A second study using the Child
      Behavior Checklist (CBCL) showed relatively high (albeit subclinical) levels of
      internalizing problems. These descriptive investigations lacked a control group.
      We describe a comparative survey to evaluate the behavioral and temperamental
      features of children with CS. We conducted a cross-sectional assessment using the
      CBCL and the Emotionality, Activity, Shyness, Sociability (EAS) temperament
      questionnaire to evaluate behavior and temperament in 11 CS children (2 years 5
      months to 9 years) comparing them to 33 gender- and age-matched children without
      disability. The results suggest that the high levels of internalizing problems
      found before age 4 in CS patients might decrease with age. They also point to
      possible "hyperemotionality." Further studies using a larger sample size and IQ
      matched control groups are needed to more accurately characterize individuals
      with this rare syndrome.

PMID- 16575891
TI  - Fumarase deficiency caused by homozygous P131R mutation and paternal partial
      isodisomy of chromosome 1.
AB  - We report on the first case of fumarase deficiency (FD) caused by uniparental
      isodisomy. An affected patient was found to be homozygous for the P131R mutation
      in the FH gene. In this nonconsanguineous family, the unaffected father was found
      to be heterozygous for the same mutation, and the mother was found to be
      homozygous wild-type. Analysis of chromosome 1 markers showed that the patient
      inherited both paternal alleles with complete absence of the maternal homolog.
      The two copies of the paternal chromosome 1 are heterodisomic for most of the
      chromosome except the distal 1q region which is isodisomic for the mutant alleles
      of the FH gene. The genotypes of other chromosome markers are consistent with the
      patient inheriting alleles from both parents. Although FD is an autosomal
      recessive disorder, the effects of uniparental disomy (UPD) should be considered
      in genetic counseling since the recurrence risk of an affected child is
      significantly reduced when the disorder is due to UPD.

PMID- 16575892
TI  - A prospective study of PHACE syndrome in infantile hemangiomas: demographic
      features, clinical findings, and complications.
AB  - PHACE (OMIM no. 606519) is a neurocutaneous syndrome that refers to the
      association of large, plaque-like, "segmental" hemangiomas of the face, with one
      or more of the following anomalies: posterior fossa brain malformations, arterial
      cerebrovascular anomalies, cardiovascular anomalies, eye anomalies, and ventral
      developmental defects, specifically sternal defects and/or supraumbilical raphe.
      The etiology and pathogenesis of PHACE is unknown, and potential risk factors for
      the syndrome have not been systematically studied. The purpose of this study was
      thus to determine (1) the incidence of PHACE and associated anomalies among a
      large cohort of hemangioma patients, (2) whether certain demographic, prenatal or
      perinatal risk factors predispose infants to this syndrome, and (3) whether the
      cutaneous distribution of the hemangioma can be correlated to the types of
      anomalies present. We undertook a prospective, cohort study of 1,096 children
      with hemangiomas, 25 of whom met criteria for PHACE. These 25 patients
      represented 20% of infants with segmental facial hemangiomas. Compared to
      previous reports, our PHACE patients had a higher incidence of cerebrovascular
      and cardiovascular anomalies. Two developed acute arterial ischemic stroke during
      infancy, while two with cardiovascular anomalies showed documented evidence of
      normalization, suggesting that both progressive and regressive vascular phenomena
      may occur in this syndrome. Correlation to the anatomic location of the
      hemangioma appears to be helpful in determining which structural abnormalities
      might be present. A comparison of demographic and perinatal data between our
      PHACE cases and the hemangioma cohort overall showed no major differences, except
      a trend for PHACE infants to be of slighter higher gestational age and born to
      slightly older mothers. Eighty-eight percent were female, a finding which has
      been noted in multiple other reports. Further research is needed to determine
      possible etiologies, optimal evaluation, and outcomes.

PMID- 16575893
TI  - Trisomy 18 in a second 20-year-old woman.

PMID- 16575894
TI  - Clarification of data reported in "cleidocranial dysplasia: molecular genetic
      analysis and phenotypic-based description of a Middle European patient group"
      (AJMG 139A:78-85).

PMID- 16575895
TI  - Familial Klippel-Feil anomaly and t(5;8)(q35.1;p21.1) translocation.

PMID- 16575896
TI  - Reporting genetic results in research studies: summary and recommendations of an
      NHLBI working group.
AB  - Prospective epidemiologic studies aid in identifying genetic variants associated
      with diseases, health risks, and physiologic traits. These genetic variants may
      eventually be measured clinically for purposes of diagnosis, prognosis, and
      treatment. As evidence of the potential clinical value of such information
      accrues, research studies face growing pressure to report these results to study
      participants or their physicians, even before sufficient evidence is available to
      support widespread screening of asymptomatic persons. There is thus a need to
      begin to develop consensus on whether and when genetic findings should be
      reported to participants in research studies. The National Heart, Lung, and Blood
      Institute (NHLBI) convened a Working Group on Reporting Genetic Results in
      Research Studies to discuss if, when, and how genetic information should be
      reported to study participants. The Working Group concluded that genetic test
      results should be reported to study participants when the associated risk for the
      disease is significant; the disease has important health implications such as
      premature death or substantial morbidity or has significant reproductive
      implications; and proven therapeutic or preventive interventions are available.
      Finally, the Working Group recommended procedures for reporting genetic research
      results and encouraged increased efforts to create uniform guidelines for this
      activity.

PMID- 16575897
TI  - Extremely high prevalence of neural tube defects in a 4-county area in Shanxi
      Province, China.
AB  - BACKGROUND: In the past, northern China's Shanxi Province has reported the
      highest incidence of neural tube defects (NTDs) in the world. However, little is
      known about the epidemiology of NTDs in this area in recent years. METHODS: Data
      were collected from a population-based birth defects surveillance system in 4
      counties that captures information on all live births, stillbirths of at least 20
      weeks' gestation, and pregnancy terminations at any gestational age resulting
      from prenatal diagnosis of a birth defect. We also surveyed mothers of NTD case
      patients to determine their use of folic acid before and during early pregnancy.
      RESULTS: During 2003, 160 NTD cases were identified among 11,534 births (NTD
      birth prevalence = 138.7/10,000 births). The rates of anencephaly, spina bifida
      and encephalocele were 65.9, 58.1, and 14.7 per 10,000, respectively, and a
      female predominance was observed among anencephaly cases (male-to-female relative
      risk [RR], 0.49; 95% confidence interval [CI], 0.30-0.79), but not among spina
      bifida (RR, 0.90; 95% CI, 0.55-1.45) and encephalocele (RR, 1.03; 95% CI, 0.40
      2.69) cases. The percentages of pregnancy termination following prenatal
      diagnosis of anencephaly, spina bifida, and encephalocele were 50%, 41.8%, and
      35.3%, respectively. NTD birth prevalence tended to be higher among mothers aged
      <20 or > or =30 years (P = .06) and was markedly associated with lower levels of
      maternal education (P < .001). Among 143 NTD mothers, only 6 (4.2%) used folic
      acid supplements during the periconceptional period. CONCLUSIONS: The NTD birth
      prevalence rate in the study area is among the highest worldwide. Folic acid
      deficiency may be one important risk factor.

PMID- 16575898
TI  - Fat intake and the risk of gastroschisis.
AB  - BACKGROUND: Young age has been associated with an increased risk of
      gastroschisis. It has been suggested that the pathogenesis of gastroschisis may
      be related to vascular disruption. Nutrients that may be associated with
      vasoconstriction include dietary fat and its subtypes. The objective of this
      study was to examine the association between dietary fats and gastroschisis and
      whether maternal age modified this association. METHODS: Data came from the
      National Birth Defects Prevention Study (NBDPS), which included 304 isolated
      gastroschisis cases and 3313 controls. Dietary intake in the year prior to
      conception was ascertained using a food frequency questionnaire, and included
      total, saturated, monosaturated, and polyunsaturated fat and cholesterol.
      Unconditional logistic regression was used to estimate the odds ratios (ORs) and
      95% confidence intervals (CIs), adjusting for confounders. Age and smoking were
      tested as effect modifiers. RESULTS: Higher mean intakes of total energy, total
      fat, and cholesterol as well as the subtypes of fats were found for gastroschisis
      cases compared to controls. Cases were more likely to be in the middle (adjusted
      OR [AOR], 1.3; 95% CI, 0.9-1.9) and highest (AOR, 1.2; 95% CI, 0.8-1.7) tertile
      of total fat intake compared to controls. This pattern was also true for
      saturated fat intake. No association was found for mono or polyunsaturated fat.
      Cases were less likely to be in the middle (AOR, 0.6; 95% CI, 0.4-0.9) and
      highest (AOR, 0.8; 95% CI, 0.6-1.2) tertiles for cholesterol. There was no
      evidence of effect modification. CONCLUSIONS: A possible weak effect of increased
      risk of gastroschisis associated with higher intakes of total fat or saturated
      fat was found in the NBDPS; however, this did not help to explain why younger
      aged women are at greater risk of having an infant with this type of birth
      defect.

PMID- 16575899
TI  - Maternal polymorphisms 677C-T and 1298A-C of MTHFR, and 66A-G MTRR genes: is
      there any relationship between polymorphisms of the folate pathway, maternal
      homocysteine levels, and the risk for having a child with Down syndrome?
AB  - This study was aimed at analyzing the effect of mutations in three non-synonymous
      SNP genes (677C > T and 1298A > C of the methylenetetrahydrofolate reductase
      (MTHFR) gene, and 66A > G in the MTRR gene) on total plasmatic homocysteine
      (Hcy), in 91 mothers of Down syndrome (DS) infants and 90 control mothers. The
      comparison of both groups of mothers is a new way to determine if those mutations
      and their interactions increase the risk for DS. Material came from the case
      control network of the Spanish Collaborative Study of Congenital Malformations
      (ECEMC). Using a general lineal model in a backwards step, we performed the
      analyses including the different mutations, maternal age, the fact that each
      mother had a DS or a control infant, and all possible interactions of these
      variables, in the models, being maternal Hcy the continuous dependent variable.
      In another model, maternal folic acid intake during the third trimester of
      pregnancy was added. The results from both models were essentially the same: Hcy
      levels variability differs from case mothers to control ones, the presence of the
      MTHFR1298A > C polymorphism also affects significantly the Hcy variance, as it
      does the statistical interaction between the mutations MTRR66A > G and MTHFR1298A
      > C in the mother. In this sense, the interaction between different polymorphisms
      may totally modify their individual effects, and some of those effects are
      different in mothers of DS children and in controls' mothers. For instance, only
      two mutations in MTRR66 (GGAA) in mothers of control infants increase the
      reference maternal Hcy level in 4.66 units, and the individual effect of the
      genotype with only two mutations in the MTHFR1298 gene (AACC) increases the
      reference Hcy level in 12.74 units. However, the presence of the four mutations
      (GGCC) interacts giving a statistically significant decrease in 6.00 units in the
      level of Hcy in control mothers. On the contrary, in mothers of DS infants, the
      sole presence of two mutations in one of these two genes decreases the levels of
      Hcy (-2.31 units for GGAA genotype, and -3.43 units for AACC genotype), while the
      presence of the four mutations (GGCC) increases Hcy in 9.53 units. Taking into
      consideration that in the one-carbon metabolism cystathionine beta-synthase (CBS)
      catalyzes Hcy in an irreversible way, and that CBS gene is located in chromosome
      21, fetuses and infants with DS have functional folate deficiency due to
      overexpression of CBS. This fact, as well as others influencing Hcy levels (such
      as nutrients interactions and lifestyle), together with the fetal genotype,
      suggest that their relationship with DS could be through an effect on fetal
      survival up to birth. Three possible mechanisms are considered by evaluating the
      results in the light of the present knowledge on cytology and molecular biology.

PMID- 16575900
TI  - Mesenchymal multipotency of adult human periosteal cells demonstrated by single
      cell lineage analysis.
AB  - OBJECTIVE: To investigate whether periosteal cells from adult humans have
      features of multipotent mesenchymal stem cells (MSCs) at the single-cell level.
      METHODS: Cell populations were enzymatically released from the periosteum of the
      proximal tibia obtained from adult human donors and then expanded in monolayer.
      Single-cell-derived clonal populations were obtained by limiting dilution.
      Culture-expanded periosteal cell populations were tested for their growth
      potential and for expression of conventional markers of MSCs and were subjected
      to in vitro assays to investigate their multilineage potential. To assess their
      multipotency in vivo, periosteal cells were injected into a regenerating mouse
      tibialis anterior muscle for skeletal myogenesis or were either seeded into an
      osteoinductive matrix and implanted subcutaneously into nude mice for
      osteogenesis or implanted in a joint surface defect under a periosteal flap into
      goats for chondrogenesis. Cell phenotypes were analyzed by histochemistry and
      immunohistochemistry and by reverse transcription-polymerase chain reaction for
      the expression of lineage-related marker genes. RESULTS: Regardless of donor age,
      periosteal cells were clonogenic and could be expanded extensively in monolayer,
      maintaining linear growth curves over at least 30 population doublings. They
      displayed long telomeres and expressed markers of MSCs. Under specific
      conditions, both parental and single-cell-derived clonal cell populations
      differentiated to the chondrocyte, osteoblast, adipocyte, and skeletal myocyte
      lineages in vitro and in vivo. CONCLUSION: Our study demonstrates that,
      regardless of donor age, the adult human periosteum contains cells that, upon
      enzymatic release and culture expansion, are multipotent MSCs at the single-cell
      level.

PMID- 16575901
TI  - Wnt induction of chondrocyte hypertrophy through the Runx2 transcription factor.
AB  - We investigated the molecular mechanisms underlying canonical Wnt-mediated
      regulation of chondrocyte hypertrophy using chick upper sternal chondrocytes.
      Replication competent avian sarcoma (RCAS) viral over-expression of Wnt8c and
      Wnt9a, upregulated type X collagen (col10a1) and Runx2 mRNA expression thereby
      inducing chondrocyte hypertrophy. Wnt8c and Wnt9a strongly inhibited mRNA levels
      of Sox9 and type II collagen (col2a1). Wnt8c further enhanced canonical bone
      morphogenetic proteins (BMP-2)-induced expression of Runx2 and col10a1 while
      Wnt8c and Wnt9a inhibited TGF-beta-induced expression of Sox9 and col2a1. Over
      expression of beta-catenin mimics the effect of Wnt8c and Wnt9a by upregulating
      Runx2, col10a1, and alkaline phosphatase (AP) mRNA levels while it inhibits
      col2a1 transcription. Western blot analysis shows that Wnt8c and beta-catenin
      also induces Runx2 protein levels in chondrocytes. Thus, our results indicate
      that activation of the canonical beta-catenin Wnt signaling pathway induces
      chondrocyte hypertrophy and maturation. We further investigated the effects of
      beta-catenin-TCF/Lef on Runx2 promoter. Co-transfection of lymphoid enhancer
      factor (Lef1) and beta-catenin in chicken upper sternal chondrocytes together
      with deletion constructs of the Runx2 promoter shows that the proximal region
      spanning the first 128 base pairs of this promoter is responsible for the Wnt
      mediated induction of Runx2. Mutation of the TCF/Lef binding site in the -128
      fragment of the Runx2 promoter resulted in loss of its responsiveness to beta
      catenin. Additionally, gel-shift assay analyses determined the DNA/protein
      interaction of the TCF/Lef binding sites on the Runx2 promoter. Finally, our site
      directed mutagenesis data demonstrated that the Runx2 site on type X collagen
      promoter is required for canonical Wnt induction of col10a1. Altogether we
      demonstrate that Wnt/beta-catenin signaling is regulated by TGF-beta and BMP-2 in
      chick upper sternal chondrocytes, and mediates chondrocyte hypertrophy at least
      partly through activation of Runx2 which in turn may induce col10a1 expression.

PMID- 16575902
TI  - Secreted frizzled related protein 1 regulates Wnt signaling for BMP2 induced
      chondrocyte differentiation.
AB  - Canonical Wnt signaling (beta-catenin/TCF) has emerged as a key regulator of
      skeletogenesis. In this study, chondrogenesis is examined in a mouse model in
      which the Wnt antagonist secreted frizzled related protein 1 (sFRP1) is non
      functional and results in a high bone mass phenotype and activation through the
      canonical pathway of the Runx2 transcription factor that is essential for bone
      formation. We find during the period of rapid post-natal growth, shortened height
      of the growth plate and increased calcification of the hypertrophic zone (HZ) in
      the sFRP1-/- mouse, indicating accelerated endochondral ossification. Using mouse
      embryo fibroblasts (MEFs) induced into the chondrogenic lineage, increased
      chondrogenesis and accelerating differentiation of hypertrophic chondrocytes in
      the sFRP1-/- MEFs was observed compared to WT cells. The induced maturation of
      hypertrophic chondrocytes in sFRP1(-/-) MEFs was inversely correlated to phospho
      beta-catenin levels, indicating involvement of activated canonical Wnt signaling
      characterized by an increased expression of collagen type 2a1 and Sox 9. However,
      an absence of Indian hedgehog expression which occurs in WT cells was found.
      SFRP1-/- cells also exhibited an early induction of collagen type 10a1. Thus,
      these modifications in gene expression are contributing mechanism(s) for
      increased chondrocyte differentiation in SFRP1-/- cells. These studies have
      identified sFRP1 as a critical negative regulator of Wnt signaling for the normal
      progression of chondrocyte differentiation. Microarray gene profiling provided
      additional novel insights into the regulatory factors for appropriate Wnt
      signaling necessary for the control of chondrocyte maturation.

PMID- 16575903
TI  - SLURP-2: A novel cholinergic signaling peptide in human mucocutaneous epithelium.
AB  - The biologic role of novel cholinergic toxin-like signaling peptides termed SLURP
      (secreted mammalian Ly-6/uPAR-related protein) in the mucocutaneous epithelium is
      a subject of intense research. Previous studies demonstrated that SLURP-1
      activates the alpha7 subtype of keratinocyte nicotinic acetylcholine receptors
      (nAChRs) and facilitates keratinization and programmed cell death, and that the
      level of SLURP-2 was found to be upregulated several fold in the
      hyperproliferative skin of patients with psoriasis. In this study, we
      demonstrated for the first time that human epidermal and oral keratinocytes
      secrete SLURP-2. We cloned human SLURP-2 and produced the mouse monoclonal
      antibody 341F10-1F12 that visualized SLURP-2 in the cytoplasm of normal human
      epidermal and oral keratinocytes grown in culture. In epidermis, SLURP-2 was
      found predominantly in the suprabasal compartment, whereas in the attached
      gingiva-in the lowermost epithelial layers. Recombinant SLURP-2 (rSLURP-2)
      competed with nicotinic radioligands for binding to keratinocytes, showing a
      higher affinity to the [3H]epibatidine- than [3H]nicotine-labeled sites.
      Treatment with rSLURP-2 significantly (P < 0.05) increased the number of
      keratinocytes in culture and their resistance to apoptosis, which could be
      abolished by mecamylamine more efficiently than alpha-bungarotoxin. By real-time
      PCR and in-cell western, rSLURP-2 significantly (P < 0.05) downregulated gene
      expression of the differentiation markers loricrin, filaggrin, and cytokeratins 1
      and 10, and pro-apoptotic Bax, Bad, and caspase 3 which were elevated by high
      extracellular calcium, and rSLURP-2 also abolished activation of caspases 3 and 8
      caused by camptothecin. These results indicated that SLURP-2 competes with
      acetylcholine predominantly at the alpha3 nAChR, and that receptor ligation with
      SLURP-2 delays keratinocyte differentiation and prevents apoptosis. Thus, the
      different effects observed for SLURP-1 and -2 can be explained by their
      differential binding to the nAChR subtypes expressed in keratinocytes. These
      findings present a novel paradigm of the physiologic regulation of mucocutaneous
      epithelial cells by locally produced small hormone-like peptide molecules, and
      open novel directions toward better understanding and treating of skin and
      mucosal diseases.

PMID- 16575904
TI  - p16 inhibits matrix metalloproteinase-2 expression via suppression of Sp1
      mediated gene transcription.
AB  - Previous studies demonstrate that p16, a cyclin-dependent kinase inhibitor and a
      tumor suppressor, may inhibit matrix metalloproteinase-2 (MMP-2) expression in
      human cancer cells to suppress tumor invasion and metastasis. However, the
      detailed mechanism is still unclear. Our results show that p16 inhibits MMP-2
      expression via transcriptional repression. Promoter deletion and mutation
      analysis indicates that p16 acts through the Sp1 transcription factor-binding
      site located between -72 and -64 bp region from the transcriptional start site of
      the human MMP-2 promoter to repress gene expression. DNA affinity precipitation
      assay (DAPA) and chromatin immuno-precipitation (CHIP) assay demonstrate that Sp1
      proteins constitutively bind to this consensus sequence in vitro and in vivo. p16
      attenuates Sp1 binding to the MMP-2 promoter to suppress gene transcription and
      overexpression of Sp1 may counteract p16-induced downregulation of MMP-2.
      CyclinA/CDK complex may directly phosphorylate Sp1 and enhance its DNA-binding
      activity. Thus, we investigated the effect of p16 on the interaction between
      cyclin A and Sp1. Our results indicate that p16 induces downregulation of cyclin
      A and CDK2, reduces the interaction between cyclin A and Sp1, and attenuates
      phosphorylation of Sp1. Ectoexpression of cyclin A counteracts p16-mediated
      inhibition of DNA binding of Sp1 and activates MMP-2 promoter activity and mRNA
      expression. Collectively, our results suggest that p16 suppresses MMP-2 by
      blocking Sp1-mediated gene transcription.

PMID- 16575905
TI  - Increased sensitivity to the platelet-derived growth factor (PDGF) receptor
      inhibitor STI571 in chemoresistant glioma cells is associated with enhanced PDGF
      BB-mediated signaling and STI571-induced Akt inactivation.
AB  - The platelet-derived growth factor receptor (PDGFR) is a tyrosine kinase,
      implicated in the development and progression of different tumors, including
      gliomas. Chemoresistance is a common feature of malignant gliomas. Since receptor
      tyrosine kinases contribute to chemoresistance in tumors, we addressed whether
      PDGFR signaling might confer selective growth advantage to chemoresistant cells.
      The effects of the PDGFR inhibitor STI571 on proliferation and PDGFR signaling
      were compared in chemosensitive and cisplatin-selected, chemoresistant sublines
      derived from glioma and from two other PDGFR-expressing tumors (ovarian carcinoma
      and neuroblastoma). The chemoresistant glioma U87/Pt cells were twofold more
      sensitive to STI571 growth-inhibitory effects than the chemosensitive U87 cells,
      and two- to threefold more sensitive than five unrelated glioma cell lines. The
      other two paired cell lines were equally responsive. Sensitization of U87/Pt
      cells correlated with upregulation of the PDGF-B isoform and with PDGF-BB-induced
      Akt overactivation, which was prevented by STI571. STI571 specifically inhibited
      PDGF-BB-, but not PDGF-AA- or stem cell factor-mediated signaling. In serum
      containing medium, STI571 decreased phospho-Akt in U87/Pt cells, but not in U87,
      while activating extracellular signal-regulated kinase (Erk) in both. STI571
      antiproliferative effects were partially reverted by constitutively active Akt.
      Cotreatment with inhibitors of phosphatidylinositol 3'-kinase (PI3K) or mitogen
      activated protein kinase kinase (MEK) resulted in enhanced growth inhibition in
      glioma cells. Our results suggest that increased PDGF-BB signaling may sensitize
      chemoresistant glioma cells to STI571, suggesting a therapeutic potential for
      STI571 in patients with malignant gliomas refractory to chemotherapy.
      Simultaneous blockade of PDGFR and PI3K or Erk pathway may enhance therapeutic
      targeting in gliomas.

PMID- 16575906
TI  - Nitric oxide and p38 MAP kinase mediate shear stress-dependent inhibition of MMP
      2 production in microvascular endothelial cells.
AB  - Chronic exposure of the skeletal muscle microcirculation to elevated shear stress
      induces angiogenesis. Previous studies observed that shear stress-induced
      capillary growth involves luminal sprouting, or internal division, of the
      capillaries, which is characterized by a minimal proliferative response and the
      retention of an intact basement membrane. Matrix metalloproteinases (MMPs) are
      associated with the process of abluminal sprouting angiogenesis, but may not be
      required for the process of luminal division during capillary growth. We analyzed
      the production of MMP-2, using both the in vivo model of prazosin-induced
      angiogenesis in rat skeletal muscle, and cultured microvascular endothelial cells
      exposed to laminar shear stress. We found that MMP-2 was not elevated in
      capillaries of shear stress-stimulated skeletal muscle, despite a significant
      increase in capillary number in response to a shear stress stimulus. In cultured
      microvascular endothelial cells, MMP-2 mRNA and protein levels were attenuated
      significantly in response to shear stress exposure. This effect on MMP-2 was
      reversed by nitric oxide (NO) synthase inhibition using LNNA. In contrast,
      exposure of static cultures of endothelial cells to NO donors significantly
      reduced MMP-2 production. Shear stress exposure and NO donors both modified
      phosphorylation levels of several members of the MAPK family. Treatment of shear
      stress-exposed cells with the p38 MAPK inhibitor, SB203580, abolished the shear
      stress-mediated reduction in MMP-2 mRNA. Thus, our data provide strong evidence
      that elevated shear stress inhibits MMP-2 production in microvascular endothelial
      cells, an effect that is mediated by signal pathways involving both production of
      NO and activation of p38 MAPK.

PMID- 16575907
TI  - Molecular and cellular characterization of mesenchymal progenitors for skeletal
      biomedical devices.
AB  - Mesenchymal cells are successfully used to create cell-loaded devices in tissue
      engineering. Molecular properties of the cells and interaction with polymer
      scaffolds regulate the development of desired tissues. The present study compared
      the molecular markers in mesenchymal pleuripotent C3H10T1/2 and osteogenic MBA-15
      cells. The cells express transcription factors (TF) of chondro-ostegenic pathway
      (cbfa-1 and c-fos) and MyoD - TF of muscle differentiation pathway, but not
      myogenin. Analyzed cells expressed receptors for glucocorticoids, growth hormone,
      prolactin, and PTH, which indicates their potential responsiveness to systemic
      signals. Analysis of mRNA encoding for receptors of TGFbeta, TNF, and various
      interleukins revealed differential expression of IL-2r and TGFbeta-1r receptors,
      which were expressed by MBA-15 but not by C3H10T1/2 cells. Expression of
      functional genes indicates differences in the stages of cell differentiation: ALK
      was present in MBA-15 only, while both cell types expressed collagen-I.
      Furthermore, we evaluated the expression of adhesion proteins that mediate cell
      polymer interactions by flow cytometry analysis. Cell adhesion molecules (CAMs)
      analyzed were integrinalpha-M (CD11b), selectin-E (CD62E), and PECAM-1 (CD31),
      which have shown differential expression on cells cultured on plastic, poly(L
      lactic acid) (PLLA) or poly(DL-lactide-glycolide acid) (PDLGA) polymer films.
      Detailed molecular characterization of mesenchymal cells will enable optimization
      of culture conditions for successful creation of implantable cell-loaded
      constructs.

PMID- 16575908
TI  - In vitro and in vivo proposal of an artificial esophagus.
AB  - Artificial materials and autologous tissues used for esophageal reconstruction
      often induce complications like stenosis and leakage at long-term follow-up. This
      study evaluates the possibility to obtain in vitro an implantable tissue
      engineered esophagus composed of homologous esophageal acellular matrix and
      autologous smooth muscle cells (SMCs). Acellular matrices obtained by detergent
      enzymatic method did not present any major histocompatibility complex marker and
      expressed bFGF as protein, showing angiogenic activity in vivo on the chick
      embryo chorioallantoic membrane (CAM). Moreover, they supported cell adhesion,
      and inasmuch as just after 24 h from seeding, the scaffold appeared completely
      covered by SMCs. To verify the biocompatibility of our constructs, defects
      created in the porcine esophageal wall were covered using homologous acellular
      matrices with and without cultures of autologous SMCs. At 3 week from surgery,
      the patches composed of only acellular matrices showed a more severe inflammatory
      response and were negative for alpha-smooth muscle actin immunostaining. In
      contrast, the cell-matrix implants presented ingrowth of SMCs, showing an early
      organization into small fascicules. Collectively, these results suggest that
      patches composed of homologous esophageal acellular matrix and autologous SMCs
      may represent a promising tissue-engineering approach for the repair of
      esophageal injuries.

PMID- 16575909
TI  - Soluble sustained release gene delivery system.
AB  - Delivery of genetic substance to target cells remains an obstacle for efficient
      utilization of gene therapy approaches. In this study, we describe a formulation
      of methacrylate acid copolymer carrier of DNA, in which the release rate of the
      gene can be controlled by pH. Plasmid release was coupled with the polymer's
      dissolution, which was accelerated in alkali conditions. The released plasmid was
      intact and bioactive, although alteration from closed circular supercoil to
      relaxed conformation was observed. Confocal laser scanning microscopy detected
      the plasmid DNA along the central layers of the polymeric film. Gene delivery
      systems controlled by the dissolution of the polymeric films offer flexibility in
      quantity and size of the incorporated DNA, and therefore could have a potential
      for in vivo use.

PMID- 16575910
TI  - Controlling biofilm formation with an N-halamine-based polymeric additive.
AB  - An N-halamine-based polymeric additive, poly[(6-morpholino-s-triazine-2,4-diyl)-N
      chloro-[2,2,6,6-tetramethyl-4-piperidyl)imino]-hexamethylene[(2,2,6,6-4
      piperidyl) imino]] (APA-1), was prepared in this study. The chemical structure of
      APA-1 was confirmed by iodometric titration, (1)H NMR, and (13)C NMR analysis.
      APA-1 was incorporated into polyurethane through solvent casting. The resultant
      materials demonstrated potent antimicrobial functions against Staphylococcus
      epidermidis. Zone of inhibition studies showed that APA-1 inactivated the
      bacteria through contact, without leaching out of the polyurethane samples. In
      vitro studies illustrated that APA-1-containing polyurethane could prevent the
      colonization and biofilm formation of S. epidermidis for at least 28 days.

PMID- 16575911
TI  - Subcutaneous evaluation of RF magnetron-sputtered calcium pyrophosphate and
      hydroxylapatite-coated Ti implants.
AB  - The in vivo behavior of infrared-heated, RF magnetron-sputtered hydroxylapatite
      (HA) and calcium pyrophosphate (DCPP) coated titanium discs was investigated. The
      discs were implanted subcutaneously in the back of six goats for 2, 4, 8 and 12
      weeks. At the end of the study, coated discs were removed and examined on their
      physicochemical properties by X-ray diffraction (XRD) and scanning electron
      microscopy (SEM), including energy dispersive spectroscopy (EDS). Also, implants
      were prepared for light microscopical evaluation of the tissue response. The
      results showed that heat-treated HA coatings showed a stable behavior, i.e. no
      changes in the XRD pattern occurred during implantation. Also, no dissolution of
      the coating was observed by SEM. EDS revealed that the Ca/P ratio of the HA
      coatings remained stable during implantation. In contrast, heat-treated DCPP
      coatings showed a compositional change into apatite and tricalcium phosphate
      (TCP) during implantation. This was confirmed by the SEM and EDS analysis. The
      Ca/P ratio of the DCPP coatings changed from 0.8 to 1.52 during implantation.
      Finally, histology showed that both heat-treated HA and DCPP coatings showed no
      adverse tissue response, as characterized by the presence of thin, dense fibrous
      tissue capsule. Consequently, it can be concluded that 2 mum thick heat-treated,
      RF magnetron-sputtered HA and DCPP coatings are of sufficient thickness to
      withstand dissolution during 12 weeks of implantation in a subcutaneous location
      in goats. In addition, both coatings showed a biocompatible tissue behavior.
      Further, heat-treated DCPP coatings revealed a gradual compositional change into
      apatite and TCP.

PMID- 16575912
TI  - Porous gelatin-chondroitin-hyaluronate tri-copolymer scaffold containing
      microspheres loaded with TGF-beta1 induces differentiation of mesenchymal stem
      cells in vivo for enhancing cartilage repair.
AB  - The aim of the study was to produce a novel porous gelatin-chondroitin
      hyaluronate scaffold in combination with a controlled release of transforming
      growth factor beta1 (TGF-beta1), which induced the differentiation of mesenchymal
      stem cells (MSCs) in vivo for enhancing cartilage repair. Gelatin microspheres
      loaded with TGF-beta1 (MS-TGFbeta1) showed a fast release at the initial phase
      (37.4%), and the ultimate accumulated release was 83.1% by day 18. The autologous
      MSCs seeded on MS-TGFbeta1/scaffold were implanted to repair full-thickness
      cartilage defects in rabbits as in vivo differentiation repair group, while MSCs
      differentiated in vitro were seeded on scaffold without MS-TGFbeta1 to repair the
      contra lateral cartilage defects (n = 30). Fifteen additional rabbits without
      treatment for defects were used as control. Histology observation showed that the
      in vivo differentiation repair group had better chondrocyte morphology,
      integration, continuous subchondral bone, and much thicker newly formed cartilage
      layer when compared to in vitro differentiation repair group 12 and 24 weeks,
      postoperatively. There was a significant difference in histological grading score
      between these two experimental groups, and both showed much better repair than
      that of the control. The present study implied that the novel scaffold with MS
      TGFbeta1 might serve as a new way to induce the differentiation of MSCs in vivo
      to enhance the cartilage repair.

PMID- 16575913
TI  - Effect of molecular weight on the transfection efficiency of novel polyurethane
      as a biodegradable gene vector.
AB  - New polyurethane 2-diethylaminoethylamine-polyurethane (LGEA-PU) containing
      poly(ethylene glycol) segments and tertiary amines was synthesized. LGEA-PU self
      assembled readily with the plasmid DNA (pCMV-betagal) in HEPES buffer and was
      characterized by dynamic light scattering, zeta potential, atomic force
      microscopy, and XTT cell viability assays. To examine the effect of molecular
      weight of LGEA-PU systems on transfection, LGEA-PU systems of four different
      molecular weights (LGEA-PU99, LGEA-PU59, LGEA-PU24, and LGEA-PU7) were prepared.
      This study found that LGEA-PU99, LGEA-PU59, and LGEA-PU24 were able to bind
      plasmid DNA and yielded positively charged complexes with a nano-sized
      transfection (<200 nm). The LGEA-PU59/DNA complexes were able to transfect COS-7
      cells in vitro with higher transfection efficiency than the other LGEA-PU
      systems. These results demonstrated that molecular weights of LGEA-PU systems had
      a significant effect on transferring ability, except for LGEA-PU99, which showed
      the strongest DNA condensation. Examination of the cytotoxicity of PEI and LGEA
      PU systems revealed that LGEA-PU systems had lower cytotoxicity. In this article,
      LGEA-PU59 seemed to be a novel cationic polyurethane for gene delivery and an
      interesting candidate for further study.

PMID- 16575914
TI  - Regeneration of bicortical defects in the iliac crest of estrogen-deficient
      sheep, using new biodegradable polyurethane bone graft substitutes.
AB  - Porous scaffolds for cancellous bone graft substitutes were prepared from new
      experimental biodegradable aliphatic polyurethane elastomers with varying
      hydrophilicity. The ratios of the hydrophilic-to-hydrophobic content in the
      polymers were 30-70, 50-50, and 70-30%, respectively. The hydrophilic component
      consisted of poly(ethylene oxide) diol and the hydrophobic component of
      poly(epsilon-caprolactone) diol. To promote the materials' biological
      performance, the calcium complexing moiety, the polysaccharide, and vitamin D(3)
      were incorporated into the polymer chain upon synthesis. The scaffolds had an
      interconnected porous structure with an average pore size in the range of 300
      2,000 microm and pore-to-volume ratios of (85 +/- 5)%. The bone substitutes were
      implanted (press-fit) in biocortical 10 x 10 mm(2) defects created in the tuber
      coxae of 21 skeletally mature Warhill ewes, which were ovariectomized 12 months
      prior to implantation. At the time of euthanasia at 18 and 25 months, all the
      defects in the ilium implanted with polyurethane bone substitutes had healed with
      new bone. The extent of bone healing depended on the chemical composition of the
      polymer from which the implant was made, although for the same material there
      were animal-related differences in healing. The structure of the newly formed
      cancellous bone was radiographically and histologically similar to the native
      bone. The implants from polymers with the incorporated calcium-complexing
      additive were the most effective promoters of bone healing, followed by those
      with vitamin D(3) and polysaccharide-containing polymer. There was no bone
      healing in the control defects.

PMID- 16575915
TI  - Sphingosine kinase 1 regulates pro-inflammatory responses triggered by TNFalpha
      in primary human monocytes.
AB  - Monocytes play an important role in inflammation, angiogenesis, and
      atherosclerosis. During these processes monocytes release pre-formed
      proinflammatory mediators from granules, and synthesize de novo cytokines and
      chemokines important in the amplification of the inflammatory response. One of
      the most prominent triggers of inflammatory responses is the cytokine TNFalpha.
      However, the intracellular signaling cascades triggered by TNFalpha are not fully
      understood. In this study we investigated the roles of SPHK on the TNFalpha
      triggered responses on human primary monocytes. We show that TNFalpha rapidly
      triggers S1P generation and activation of SPHK. Moreover, our data shows that
      SPHK1 is the isoform activated by TNFalpha, and plays an essential role on the
      TNFalpha-triggered intracellular Ca2+ signals, degranulation, cytokine
      production, and activation of NFkappaB, thus suggesting a pivotal role for SPHK1
      on the proinflammatory responses triggered by TNFalpha.

PMID- 16575916
TI  - Differentiation-related changes in mitochondrial properties as indicators of stem
      cell competence.
AB  - Several methods may be used to assess stem cell competence, including the
      expression of cell surface markers and telomerase activity. We hypothesized that
      mitochondrial characteristics might be an additional and reliable way to verify
      stem cell competence. In a multipotent, adult monkey stromal stem cell line,
      previously shown to differentiate into adipocytes, chondrocytes, and osteocytes,
      we found that several mitochondrial properties change with increasing passage
      number in culture. Cells from the earliest passage (P11) versus those from a
      later passage (P17) are characterized by: (a) a much higher percentage of cells
      (85% vs. 18%) with a perinuclear arrangement of mitochondria; (b) a much lower
      percentage of cells (1% vs. 57%) with an aggregated mitochondrial arrangement, in
      which mitochondria appear to coalesce into large clumps; (c) a much lower
      percentage of cells with lipid droplets (1% vs. 36%), suggesting less
      differentiation into adipocytes; (d) a 5.6-fold lower ATP content per cell (0.45
      vs. 2.51 pmoles ATP/cell; and (e) a 10-fold higher rate of oxygen consumption
      (37.8 vs. 3.8 nmoles O2/min/10(3) cells), indicating a higher metabolic activity.
      Collectively, these data indicate that the perinuclear arrangement of
      mitochondria, accompanied by a low ATP/cell content and a high rate of oxygen
      consumption, may be valid indicators of stem cell differentiation competence,
      while departures from this profile indicate that cells are differentiating or
      perhaps becoming senescent. These results represent the first characterization of
      mitochondrial properties reported for a primate stem cell line.

PMID- 16575917
TI  - Highlights from the 5th Annual Meeting of the Italian Society of Virology.
AB  - The 5th National Congress of the Italian Society of Virology (SIV) was attended
      by junior- and senior-level virologists to promote interactions and scientific
      collaborations among the different areas of Virology and allied sciences. The
      invited and selected lecturers covered the following topics: General Virology and
      Viral Genetics; Virus-host Interaction and Pathogenesis; Viral Oncogenesis; Viral
      Immunology and Vaccines; Anti-viral Therapy; Innovative Diagnostics; Viral
      Biotechnologies and Cell and Gene Therapy. As in the previous editions (Salata
      and Palu, 2004; Salata et al., 2005), a specific topic was thoroughly covered in
      a roundtable. This year the elected subject was "HIV: determinants of
      pathogenicity and clinical implications." The final program and the abstract book
      can be found at the web site http://www.siv-virologia.it. This report summarizes
      the lessons learned from the plenary lectures and the selected oral presentations
      of the 2005 meeting.

PMID- 16575918
TI  - Increased mobilization of c-kit+ Sca-1+ Lin- (KSL) cells and colony-forming units
      in spleen (CFU-S) following de novo formation of a stem cell niche depends on
      dynamic, but not stable, membranous ossification.
AB  - Stem cells are thought to inhabit in a unique microenvironment, known as "niche,"
      in which they undergo asymmetric cell divisions that results in reproducing both
      stem cells and progenies to maintain various tissues throughout life. The cells
      of osteoblastic lineage have been identified as a key participant in regulating
      the number of hematopoietic stem cells (HSCs). HSCs receive their regulatory
      messages from the microenvironment in the bone marrow. This would account for a
      reason why the localization of hematopoiesis is usually restricted in the bone
      marrow. To clarify the above possibility we employed a cell implantation-based
      strategy with a unique osteoblast cell line (KUSA-A1) derived from a C3H/He
      mouse. The implantation of KUSA-A 1 cells resulted in the generation of ectopic
      bones in the subcutaneous tissues of the athymic BALB/c nu/nu mice. Subsequently
      the mice obtained a greater amount of the bone marrow than normal mice, and they
      showed an increased number of HSCs. These results indicate that the newly
      generated osteoblasts-derived ectopic bones are responsible for the increase in
      the number of the HSC population. Furthermore, the increased number of HSCs
      directly correlates with both the magnitude of dynamic osteogenic process and the
      size of the newly generated bone or "niche."

PMID- 16575919
TI  - Mortality, morbidity, and cost associated with febrile neutropenia in adult
      cancer patients.
AB  - BACKGROUND: Hospitalization for febrile neutropenia (FN) in cancer patients is
      associated with considerable morbidity, mortality, and cost. The study was
      undertaken to better define mortality, length of stay (LOS), cost, and risk
      factors associated with mortality and prolonged hospitalization in cancer
      patients with FN. METHODS: The longitudinal discharge database derived from 115
      US medical centers was used to study all adult cancer patients hospitalized with
      FN between 1995 and 2000, comprising a total of 41,779 patients. Primary outcomes
      included mortality, LOS, and cost per episode. RESULTS: Overall, in-hospital
      mortality was 9.5%. Patients without any major comorbidities had a 2.6% risk of
      mortality, whereas 1 major comorbidity was associated with a 10.3% and more than
      1 major comorbidity with a > or = 21.4% risk of mortality, respectively. Mean
      (median) length of stay was 11.5 (6) days, and the mean (median) cost was $19,110
      ($8,376) per episode of FN. Patients hospitalized for > or = 10 days (35% of all
      patients) accounted for 78% of overall cost. Independent major risk factors for
      inpatient mortality included invasive fungal infections, Gram-negative sepsis,
      pneumonia and other lung disease, cerebrovascular, renal, and liver disease. Main
      predictors for LOS > or = 10 days included leukemia, invasive fungal infections,
      other types of infection, and several comorbid conditions. CONCLUSION: Factors
      associated with increased mortality, LOS, and cost in hospitalized adult cancer
      patients with FN include patient characteristics, type of malignancy,
      comorbidities, and infectious complications. These factors may be useful in
      identifying patients at increased risk of serious medical complications and
      mortality for more aggressive supportive care measures.

PMID- 16575920
TI  - Functional phenotyping of human plasma using a 361-fluorogenic substrate
      biosensing microarray.
AB  - A microarray presenting glycerol nanodroplets of fluorogenic peptide substrates
      was used as a biosensor for the detection of multiple enzyme activities within
      human plasma. Using 10 different plasma proteases (kallikrein, factor XIIa,
      factor XIa, factor IXa, factor VIIa, factor Xa, thrombin, activated protein C,
      uPA and plasmin) and a 361-compound fluorogenic substrate library (Ac-Ala-P3-P2
      Arg-coumarin for P = all amino acids except Cys), a database was created for
      deconvoluting the relative activity of each individual enzyme signal in human
      plasma treated with various activators (calcium, kaolin, or uPA). Three separate
      deconvolution protocols were tested: searching for "optimal" sensing substrate
      sequences for a set of 5 enzymes and using these substrates to detect protease
      signals in plasma; ranking the "optimal" sensing substrates for 10 proteases
      using local error minimization, resulting in a set of substrates which were
      bundled via weighted averaging into a super-pixel that had biosensing properties
      not obtainable by any individual fluorogenic substrate; and treating each 361
      element map measured for each plasma preparation as a weighted sum of the 10 maps
      obtained for the 10 purified enzymes using a global error minimization. The
      similarity of the results from these latter two protocols indicated that a small
      subset of <90 substrates contained the majority of biochemical information. The
      results were consistent with the state of the coagulation cascade expected when
      treated with the given activators. This method may allow development of future
      biosensors using minimal and non-specific markers. These substrates can be
      applied to real-time diagnostic biosensing of complex protease mixtures.

PMID- 16575921
TI  - Transient renal failure due to hemolysis following transcatheter closure of a
      muscular VSD using an Amplatzer muscular VSD occluder.
AB  - Transcatheter closure of ventricular septal defects (VSDs) has become
      increasingly common. This case describes hemolysis causing renal failure and its
      spontaneous resolution following the transcatheter closure of a congenital
      muscular VSD using an Amplatzer muscular VSD occluder.

PMID- 16575923
TI  - Bioabsorbable metal stents for percutaneous treatment of critical recoarctation
      of the aorta in a newborn.
AB  - In neonates and infants with critical aortic coarctation, balloon angioplasty is
      considered for rescue therapy of heart failure. The use of conventional stents is
      limited because of further vessel growth, the need of redilation, and later
      surgical removal. However, a novel bioabsorbable magnesium stent (AMS) might
      overcome such restrictions of vessel stenting in newborns. Presented is the first
      use of an AMS for acute treatment of a newborn with severely impaired heart
      function due to a long segment recoarctation after a complex surgical repair. We
      hypothesize that bioabsorbable stents will dramatically change the treatment of
      coarctation and recoarctation in newborns.

PMID- 16575922
TI  - Stenting of the vertical vein in obstructed total anomalous pulmonary venous
      return as rescue procedure in a neonate.
AB  - A newborn girl with progressive respiratory distress and cyanosis was found to
      have severely obstructed supracardiac total pulmonary venous return (TAPVR).
      Stenting of the stenosis provided immediate and effective relief of the
      obstruction until corrective surgery was performed. Catheter intervention should
      be considered in high-risk infants with obstructed supracardiac TAPVR as part of
      the strategy for preoperative cardiovascular stabilization.

PMID- 16575924
TI  - Transhepatic closure of atrial septal defect and assisted closure of modified
      Blalock/Taussig shunt.
AB  - The details of transhepatic closure of moderate - large size atrial septal defect
      as well as assisted closure of a modified Blalock Taussig shunt in a 2 1/2 year
      old patient with occluded femoral vessels are discussed. The technical variations
      as well as the potential advantages of this route are outlined.

PMID- 16575925
TI  - A novel paclitaxel-eluting porous carbon-carbon nanoparticle coated, nonpolymeric
      cobalt-chromium stent: evaluation in a porcine model.
AB  - OBJECTIVES: We aimed to evaluate the response of porcine coronary arteries to a
      novel paclitaxel-eluting porous carbon-carbon nanoparticle coated, nonpolymeric
      cobalt chromium stent. BACKGROUND: Polymer based drug-eluting stents
      significantly reduce restenosis. However, the indefinite presence of polymer is
      thought to initiate and sustain inflammation and contribute to the occurrence of
      late complications. METHODS: Sixteen carbon-carbon coated, nonpolymeric cobalt
      chromium stents with two different doses of paclitaxel (eight of each) were
      implanted in porcine coronary arteries. In addition, eight cobalt chromium stents
      coated with a biodegradable polymer were also studied. Animals were sacrificed 6
      weeks after stent implantation and histomorphometric analysis was performed.
      Results were compared among the three groups of stents. RESULTS: The cobalt
      chromium stents coated with carbon-carbon with low and medium doses of paclitaxel
      both showed acceptable performance characteristics, with respect to
      endothelialization, neointimal hyperplasia, percentage diameter stenosis,
      inflammatory response, and tendency to fibrin deposition, when compared to
      historical data with the Cypher stent. On the other hand, the stents coated with
      poly(lactide) and poly(lactide-co-glycolide) biodegradable polymers and 0.7
      microg/mm2 paclitaxel showed poor performance. There was a significant tendency
      to poor endothelialization, greater neointimal hyperplasia, percentage diameter
      stenosis, greater inflammatory response, and tendency to fibrin deposition (P <
      0.01 for all parameters). CONCLUSIONS: This preclinical evaluation demonstrates
      the safety and efficacy of a novel cobalt chromium stent with a carbon-carbon
      coating and low and medium doses of paclitaxel.

PMID- 16575926
TI  - The paclitaxel-eluting Coroflex Please stent pilot study (PECOPS I): acute and 6
      month clinical and angiographic follow-up.
AB  - BACKGROUND AND OBJECTIVES: Various active stent coatings significantly reduce
      restenosis rates and target lesion revascularization compared to bare metal
      stents. Therefore, the procedural and 6-month performance of the new paclitaxel
      eluting Coroflex. Please stent was investigated. METHODS: Ninety-seven patients
      (66 +/- 7.6 years, 34/97(35.1%) diabetics, 11/97(11.3%) unstable angina) were
      enrolled per protocol for elective single stent deployment into native coronary
      de-novo or post-PTCA restenotic lesions (stenosis: >or= 70%, < 100%; reference
      diameter >or= 2.25 mm and <3.3 mm; lesion length <or= 16 mm) with 13/97(13.4%)
      lesion type A, 64/97(66%) type B1, 20/97(20.6%) type B2). The mean reference
      diameter was 2.88 +/- 0.42 mm, the lesion length 10.03 +/- 2.93 mm, and the
      minimal lumen diameter 0.64 +/- 0.22 mm. RESULTS: The success rates of procedure
      and study stent deployment were 100% and 94.8%, respectively. In 5/97(5.2%) two
      stents were implanted. Follow-up was performed clinically in 86/87(98.9%) and
      angiographically in 77/87(88.5%) patients after 6.1 +/- 0.7 months. Major adverse
      cardiac events occurred in 7/87(8%) 1/87(1.2%) subacute thrombosis 10.3hrs post
      procedure, 1/87(1.2%) myocardial infarction, 5/87(5.7%) target lesion
      revascularizations. The in-segment stenosis declined from 78 +/- 7.2% to 9.4 +/-
      6.2% after stenting increasing to 31.9 +/- 18.6% at follow-up. The in-segment
      late loss and the late loss index were 0.47 +/- 0.6 mm and 0.23 +/- 0.29
      resulting in 6/77(7.8%) in-segment restenoses three each of which were located
      either within or beyond the stent structure. The outcome was neither influenced
      by the prevalence of diabetes ( p = 0.4), hypercholesterolemia ( p = 1),
      hypertension ( p = 1), overweight ( p = 1), nor by the family history of coronary
      artery disease ( p = 0.7). CONCLUSION: The data of the paclitaxel-eluting
      Coroflex. Please stent tested in PECOPS I are within the range other available
      paclitaxel-eluting stent.

PMID- 16575927
TI  - A variety of spin-crossover behaviors depending on the counter anion: two
      dimensional complexes constructed by NH...Cl- hydrogen bonds, [FeIIH3LMe]Cl.X (X
      = PF6 -, AsF6 -, SbF6 -, CF3SO3 -; H3L(Me) = Tris[2-{[(2-methylimidazol-4
      yl)methylidene]amino}ethyl]amine).
AB  - A family of spin-crossover (SC) complexes, [Fe(II)H(3)L(Me)]Cl.X (X(-) = PF(6) (
      ), AsF(6) (-), SbF(6) (-), CF(3)SO(3) (-)), 1-4, has been synthesized, in which
      H(3)L(Me) denotes the hexadentate N(6) tripod-like ligand tris[2-{[(2
      methylimidazol-4-yl)methylidene]amino}ethyl]amine, containing three imidazole
      groups, with a view to establishing the effect of the counter anion on the SC
      behavior. These complexes have been found to crystallize in the same monoclinic
      crystal system with similar cell dimensions. The general crystal structure
      consists of a two-dimensional (2D) extended network constructed by NH...Cl-
      hydrogen bonds between Cl- and the imidazole NH groups of three neighboring
      [Fe(II)H(3)L(Me)]2+ ions, while the anion X exists as an isolated counter anion
      and occupies the space between the 2D sheets. Magnetic susceptibilities and
      Mossbauer spectra have revealed a variety of SC behaviors depending on the
      counter anion, including a one-step HS<==>(HS + LS)/2 (1, X = PF(6) (-)), a two
      step HS<==>(HS + LS)/2<==>LS with a slow thermal relaxation (2, X = AsF(6) (-)),
      a gradual one-step HS<==>LS (3, X = SbF(6) (-)), and a steep one-step HS<==>LS
      with hysteresis (4, X = CF(3)SO(3) (-)). The complexes assume the space group
      P2(1)/n in the HS state, P2(1) in the HS + LS state, and P2(1)/n in the LS state.
      The Fe-N bond lengths and the N-Fe-N bond angles are indicative of the HS, HS +
      LS, and LS states. The molecular volumes, V, of the counter anions have been
      evaluated by quantum-chemical calculations as follows: 53.4 A(3) (BF(4) (-)),
      54.4 A(3) (ClO(4) (-)), 73.0 A(3) (PF(6) (-)), 78.5 A(3) (AsF(6) (-)), 88.7 A(3)
      (SbF(6) (-)), and 86.9 A(3) (CF(3)SO(3) (-)). The size and shape of the counter
      anion affects the flexible 2D network structure constructed by the hydrogen
      bonds, leading to modifications of the SC behavior. These estimated relative
      sizes of the counter anions correlate well with the observed SC behaviors.

PMID- 16575928
TI  - Interaction energies for the purine inhibitor roscovitine with cyclin-dependent
      kinase 2: correlated ab initio quantum-chemical, DFT and empirical calculations.
AB  - The interaction between roscovitine and cyclin-dependent kinase 2 (cdk2) was
      investigated by performing correlated ab initio quantum-chemical calculations.
      The whole protein was fragmented into smaller systems consisting of one or a few
      amino acids, and the interaction energies of these fragments with roscovitine
      were determined by using the MP2 method with the extended aug-cc-pVDZ basis set.
      For selected complexes, the complete basis set limit MP2 interaction energies, as
      well as the coupled-cluster corrections with inclusion of single, double and
      noninteractive triples contributions [CCSD(T)], were also evaluated. The energies
      of interaction between roscovitine and small fragments and between roscovitine
      and substantial sections of protein (722 atoms) were also computed by using
      density-functional tight-binding methods covering dispersion energy (DFTB-D) and
      the Cornell empirical potential. Total stabilisation energy originates
      predominantly from dispersion energy and methods that do not account for the
      dispersion energy cannot, therefore, be recommended for the study of protein
      inhibitor interactions. The Cornell empirical potential describes reasonably well
      the interaction between roscovitine and protein; therefore, this method can be
      applied in future thermodynamic calculations. A limited number of amino acid
      residues contribute significantly to the binding of roscovitine and cdk2, whereas
      a rather large number of amino acids make a negligible contribution.

PMID- 16575929
TI  - Photochromic reactions of diarylethenes in single crystals with intermolecular O-
      H...N hydrogen-bonding networks.
AB  - The crystal structures and photochromic performance of a single crystal of a
      diarylethene derivative possessing carboxyl groups, 1,2-bis(5-carboxyl-2-methyl-3
      thienyl)perfluorocyclopentene (1 a), and cocrystals of 1 a with 4,4'-, 2,4'-, and
      2,2'-bipyridines were examined. In crystal 1 a, a discrete cyclic structure was
      observed, in which four 1 a molecules are linked through hydrogen bonds between
      the carboxyl groups. In the homocrystal, photoreactive and photoinactive
      conformers of 1 a exist in the ratio of 1:1. In the cocrystals of 1 a with
      bipyridines, O--HN-type hydrogen bonds between 1 a and pyridyl groups were
      formed, and all 1 a molecules are fixed in a photoreactive conformation. Both the
      homocrystal 1 a and the cocrystals showed photochromic performances, and color
      variation from bluish-violet to cyan was observed, depending on the conformation
      of the packed diarylethene molecules.

PMID- 16575930
TI  - Site-selective formation of optically active inclusion complexes of alkoxo
      subphthalocyanines with beta-cyclodextrin at the toluene/water interface.
AB  - Several subphthalocyanine derivatives that contain an alkoxo substituent as an
      axial ligand (RO-Subpc, R = 9-anthracenemethyl, benzyl, phenyl, 3,5
      dimethylbenzyl, 3,5-dimethylphenyl, 4-methylbenzyl, and 4-methylphenyl) were
      synthesized. The formation of inclusion complexes of RO-Subpc with beta-CD in
      DMSO and at the toluene/water interface was investigated by UV/Vis absorption
      spectroscopy, induced circular dichroism (ICD), and nuclear magnetic resonance
      (NMR) measurements. Interfacial tension measurements suggested that beta-CD
      adsorbed as a monolayer at the toluene/water interface and probably orientated
      towards the toluene phase with its primary face. The 1:1 composition of beta
      CD.RO-Subpc inclusion complexes was confirmed in DMSO and at the toluene/water
      interface for BzO-Subpc, PhO-Subpc, MeBzO-Subpc, and MePhO-Subpc. A 2:1 inclusion
      complex of AnO-Subpc formed in DMSO. The observed ICD spectra of beta-CDRO-Subpc
      inclusion complexes are discussed with respect to molecular modeling and the
      simulation based on Tinoco-Kirkwood theory. Interestingly, the ICD spectra of
      beta-CD.BzO-Subpc and beta-CD.MeBzO-Subpc inclusion complexes exhibited a
      negative sign in DMSO and a positive sign at the toluene/water interface. This
      reversal of the ICD sign strongly suggests a difference in the structure of the
      inclusion complexes: beta-CD at the interface formed the inclusion complex with
      its primary face, whereas the secondary face of beta-CD bound favorably to RO
      Subpc in DMSO.

PMID- 16575931
TI  - Dinuclear monointercalating RuII complexes that display high affinity binding to
      duplex and quadruplex DNA.
AB  - The DNA duplex binding properties of previously reported dinuclear Ru(II)
      complexes based on the ditopic ligands tetrapyrido[3,2-a:2',3'-c:3'',2''
      h:2'',3''-j]phenazine (tppz) and tetraazatetrapyrido[3,2-a:2'3'-c:3'',2''
      l:2''',3'''-n]pentacene (tatpp) are reported. Photophysical and biophysical
      studies indicate that, even at high ionic strengths, these complexes bind to
      duplex DNA, through intercalation, with affinities that are higher than any other
      monointercalating complex and are only equalled by DNA-threaded bisintercalating
      complexes. Additional studies at high ionic strengths using the 22-mer
      d(AG(3)[T(2)AG(3)](3)) [G3] human telomeric sequence reveal that the dinuclear
      tppz-based systems also bind with high affinity to quadruplex DNA. Furthermore,
      for these complexes, quadruplex binding is accompanied by a distinctive blue
      shifted "light-switch" effect, characterized by higher emission enhancements than
      those observed in the analogous duplex effect. Calorimetry studies reveal that
      the thermodynamics of duplex and quadruplex binding is distinctly different, with
      the former being entirely entropically driven and the latter being both
      enthalpically and entropically favored.

PMID- 16575932
TI  - trans-1-Sulfonylamino-2-isoborneolsulfonylaminocyclohexane derivatives: excellent
      chiral ligands for the catalytic enantioselective addition of organozinc reagents
      to ketones.
AB  - The catalytic enantioselective addition of different organozinc reagents (such as
      alkyl and aryl derivatives or in situ generated aryl, allyl alkenyl, and alkynyl
      derivatives obtained through different transmetallation processes) to simple
      ketones has been accomplished by using titanium tetraisopropoxide and chiral
      ligands derived from substituted trans-1-sulfonylamino-2
      isoborneolsulfonylaminocyclohexane, producing the corresponding tertiary alcohols
      with enantiomeric excesses (ee) up to >99 %. A simple and efficient procedure for
      the synthesis of the chiral ligands used in these reactions is described.

PMID- 16575933
TI  - Tuning the thermotropic and lyotropic properties of liquid-crystalline
      terpyridine ligands.
AB  - A rational synthetic strategy is developed to provide compact and simple
      terpyridine (terpy) mesogens that show liquid-crystallinity both as pure
      compounds and in organic solution (amphotropic compound). The use of a central 4
      methyl-3,5-diacylaminophenyl platform equipped with two lateral aromatic rings,
      each bearing three appended aliphatic chains, allows connection of a 2,2':6',2''
      terpyridine fragment through a polar group such as an ester, amide, or flat
      conjugated alkyne linker. For the T(12)ester and T(12)amide scaffolds, the
      mesophase is best described as a lamellar phase, in which the molecules self
      assemble into columnar stacks held together in layers. In the T(12)amide case,
      the additional amide link results in significant stabilization of the lamellar
      phase. The driving forces for the appearance of columnar ordering are the
      hydrogen-bonding interactions of the amide groups, which induce head-to-tail pi
      stacking of the terpy subunits. Replacing the polar linker by a nonpolarized but
      linear alkyne spacer, as in the T(12)ethynyl compound, provides a columnar
      mesophase organized in a rectangular lattice of p2gg symmetry. In this
      arrangement, two nondiscotic molecules arranged into dimers by hydrogen bonding
      and pi-pi stacking pile up in a head-to-tail manner to form columns. In addition,
      the T(12)amide compound proves to be an excellent gelator of cyclohexane, linear
      alkanes, and DMSO. The resulting robust and transparent gels are birefringent and
      formed by large aggregates that are readily aligned by shear-flow. TEM and freeze
      fracture microscopy reveal that the gels have an original layered morphology made
      of fibers.

PMID- 16575934
TI  - Methoxyperylene bisimides and perylene lactame imides: novel, red fluorescent
      dyes.
AB  - The synthesis of methoxyperylene bisimides and perylene lactame imides with
      aliphatic N-substituents is described. Both classes of dyes exhibit fluorescence
      in the bathochromic region of visible light so that red light is obtained. The
      lightfastness of the dyes is very high, thus, there is special interest for
      diverse applications.

PMID- 16575935
TI  - Squaraine-derived rotaxanes: highly stable, fluorescent near-IR dyes.
AB  - Squaraines are fluorescent, near-IR dyes with promising photophysical properties
      for biomedical applications. A limitation with these dyes is their inherent
      reactivity with nucleophiles, which leads to loss of the chromophore. Another
      drawback is their tendency to form nonfluorescent aggregates in water. Both
      problems can be greatly attenuated by encapsulating the dye inside an amide
      containing macrocycle. In other words, the squaraine becomes the thread component
      in a Leigh-type rotaxane, a permanently interlocked molecule. Two new rotaxanes
      are described: an analogue with four tri(ethyleneoxy) chains on the squaraine to
      enhance water solubility, and a rotaxane that has an encapsulating macrocycle
      with transposed carbonyl groups. An X-ray crystal structure of the latter
      rotaxane shows that the macrocycle provides only partial protection of the
      electrophilic cyclobutene core of the squaraine thread. The stabilities of each
      compound in various solvents, including serum, were compared with a commercially
      available cyanine dye. The squaraine rotaxane architecture is remarkably
      resistant to chemical and photochemical degradation, and likely to be very useful
      as a versatile fluorescent scaffold for constructing various types of highly
      stable, near-IR imaging probes.

PMID- 16575936
TI  - Fullerene polypyridine ligands: synthesis, ruthenium complexes, and
      electrochemical and photophysical properties.
AB  - Fullerene coordination ligands bearing one bipyridine or terpyridine unit were
      synthesized, and their coordination to ruthenium(II) formed linear rod-like donor
      acceptor systems. Steady-state fluorescence of [Ru(bpy)(2)(bpy-C(60))](2+) showed
      a rapid solvent-dependent, intramolecular quenching of the ruthenium(II) MLCT
      excited state. Time-resolved flash photolysis in CH(3)CN revealed characteristic
      transient absorption changes that have been ascribed to the formation of the
      C(60) triplet state, suggesting that photoexcitation of [Ru(bpy)(2)(bpy
      C(60))](2+) results in a rapid intramolecular transduction of triplet excited
      state energy. The electrochemical studies on both [Ru(bpy)(2)(bpy-C(60))](2+) and
      [Ru(tpy)(tpy-C(60))](2+) indicated electronic coupling between the metal center
      and the fullerene core.

PMID- 16575937
TI  - Enantio- and diastereoselective Michael addition reactions of unmodified
      aldehydes and ketones with nitroolefins catalyzed by a pyrrolidine sulfonamide.
AB  - Chiral (S)-pyrrolidine trifluoromethanesulfonamide has been shown to serve as an
      effective catalyst for direct Michael addition reactions of aldehydes and ketones
      with nitroolefins. A wide range of aldehydes and ketones as Michael donors and
      nitroolefins as acceptors participate in the process, which proceeds with high
      levels of enantioselectivity (up to 99 % ee) and diastereoselectivity (up to 50:1
      d.r.). The methodology has been employed successfully in an efficient synthesis
      of the potent H(3) agonist Sch 50917. In addition, a practical three-step
      procedure for the preparation of (S)-pyrrolidine trifluoromethanesulfonamide has
      been developed. The high levels of stereochemical control attending Michael
      addition reactions catalyzed by this pyrrolidine sulfonamide, have been
      investigated by using ab initio and density functional methods. Transition state
      structures for the rate-limiting C--C bond-forming step, corresponding to re- and
      si-face addition to the reactive conformation of the key enamine intermediates
      have been calculated. Analysis of these structures indicates that hydrogen
      bonding plays an important role in catalysis and that the energy barrier for si
      face attack in reactions of aldehydes to form 2R,3S products is lower than that
      for the re-face attack leading to 2S,3R products. In contrast, the energy barrier
      for re-face addition is lower than that for si-face addition in reactions of
      ketones. The computational results, which are in good agreement with the
      experimental observations, are discussed in the context of the stereochemical
      course of these Michael addition reactions.

PMID- 16575938
TI  - Probing the ligand-binding specificity and analyzing the folding state of SPOT
      synthesized FBP28 WW domain variants.
AB  - The WW domains are known as the smallest naturally occurring, monomeric, triple
      stranded, antiparallel beta-sheet domains. Hence, we chose the FBP28 WW domain as
      a model to investigate the stability of the beta-sheet structure at the amino
      acid level in the context of its function (ligand binding). The structure
      function relationship was investigated through a complete substitution analysis
      of the FBP28 WW domain, with variants synthesized as a cellulose-bound peptide
      array. The functionality of the FBP28 WW domain variants was examined by probing
      the peptide array for ligand binding. In addition, selected FBP28 WW domain
      variants were investigated by CD measurements to determine the stability of the
      antiparallel beta-sheet structure. We discuss the correlation between structure
      stability and functionality for the FBP28 WW domain, as well as the effect of
      ligand-induced structure stabilization.

PMID- 16575939
TI  - RebG- and RebM-catalyzed indolocarbazole diversification.
AB  - Rebeccamycin and staurosporine represent two broad classes of indolocarbazole
      glycoside natural products with antitumor properties. Based upon previous
      sequence annotation and in vivo studies, rebG encodes for the rebeccamycin N
      glucosyltransferase, and rebM for the requisite 4'-O-methyltransferase. In the
      current study, an efficient in vivo biotransformation system for RebG was
      established in both Streptomyces lividans and Escherichia coli. Bioconversion
      experiments revealed RebG to glucosylate a set of indolocarbazole surrogates, the
      products of which could be further modified by in vitro RebM-catalyzed 4'-O
      methylation. Both RebG and RebM displayed substrate promiscuity, and evidence for
      a remarkable lack of RebG regioselectivity in the presence of asymmetric
      substrates is also provided. In the context of the created indolocarbazole
      analogues, cytotoxicity assays also highlight the importance of 4'-O-methylation
      for their biological activity.

PMID- 16575940
TI  - Directed evolution of an esterase from Pseudomonas fluorescens yields a mutant
      with excellent enantioselectivity and activity for the kinetic resolution of a
      chiral building block.
AB  - A triple mutant of an esterase from Pseudomonas fluorescens (PFE) that was
      created by directed evolution exhibited high enantioselectivity (E=89) in a
      kinetic resolution and yielded the building block (S)-but-3-yn-2-ol.
      Surprisingly, a mutation close to the active site caused the formation of
      inclusion bodies, but remote mutations were found to be responsible for the high
      selectivity. Back mutations gave a variant (double mutant PFE Ile76Val/Val175Ala)
      that showed excellent selectivity (E=96) and activity (20 min for 50% conversion,
      which corresponds to 1.25 U per mg of protein).

PMID- 16575942
TI  - Common pain reliever may promote social interaction in people with dementia.

PMID- 16575943
TI  - Omega-3 no magic bullet for cancer.

PMID- 16575944
TI  - Stem cell infusions after MI bring mixed results.

PMID- 16575941
TI  - The stacked-X DNA Holliday junction and protein recognition.
AB  - The crystal structure of the four-stranded DNA Holliday junction has now been
      determined in the presence and absence of junction binding proteins, with the
      extended open-X form of the junction seen in all protein complexes, but the more
      compact stacked-X structure observed in free DNA. The structures of the stacked-X
      junction were crystallized because of an unexpected sequence dependence on the
      stability of this structure. Inverted repeat sequences that contain the general
      motif NCC or ANC favor formation of stacked-X junctions, with the junction cross
      over occurring between the first two positions of the trinucleotides. This review
      focuses on the sequence dependent structure of the stacked-X junction and how it
      may play a role in structural recognition by a class of dimeric junction
      resolving enzymes that themselves show no direct sequence recognition.

PMID- 16575945
TI  - Milk. It's for your lungs.

PMID- 16575946
TI  - Meds and the restless search for sleep.

PMID- 16575947
TI  - [About the consensus statement "Pregnancy and tobacco" (Lille,7-8 October,
      2004)].

PMID- 16575948
TI  - Norman Shumay.

PMID- 16575949
TI  - Infliximab for ulcerative colitis.

PMID- 16575950
TI  - Infliximab for ulcerative colitis.

PMID- 16575951
TI  - Clinical trials report card.

PMID- 16575952
TI  - Clinical trials report card.

PMID- 16575953
TI  - Clinical trials report card.

PMID- 16575954
TI  - Clinical trials report card.

PMID- 16575955
TI  - Community-acquired bacterial meningitis.

PMID- 16575956
TI  - Community-acquired bacterial meningitis.

PMID- 16575957
TI  - Community-acquired bacterial meningitis.

PMID- 16575958
TI  - Community-acquired bacterial meningitis.

PMID- 16575959
TI  - An Attempt to Measure the Free Electricity in the Sun's Atmosphere.

PMID- 16575960
TI  - Results of an Investigation of the Flash Spectrum Without an Eclipse: Region
      lambda 4800 TO lambda 6600.

PMID- 16575962
TI  - An Experimental Study of Lipolytic Actions.

PMID- 16575961
TI  - Variability of Spectrum Lines in the Iron Arc.

PMID- 16575963
TI  - The Hydration of the Ions of Cesium Chloride Derived from Transference
      Experiments in the Presence of Raffinose.

PMID- 16575964
TI  - The Origin of Coral Reefs.

PMID- 16575965
TI  - A Method of Prophesying the Life Duration of Seeds.

PMID- 16575966
TI  - The Fertilizing Power of Sperm Dilutions of Arbacia.

PMID- 16575967
TI  - Variation in Bacteria.

PMID- 16575969
TI  - A Note on Functions of Lines.

PMID- 16575968
TI  - A Dynamic Conception of the Organic Individual.

PMID- 16575970
TI  - A Classification of Quadratic Vector Functions.

PMID- 16575972
TI  - Notices of Scientific Memoirs.

PMID- 16575971
TI  - On the Radial Velocities of Five Nebulae in the Magellanic Clouds.

PMID- 16575973
TI  - Photographic Determination of Stellar Parallaxes with the 60-inch Reflector.

PMID- 16575974
TI  - On Chondrosamine.

PMID- 16575975
TI  - The Freezing-Point-Solubility Law for Ideal Solutions.

PMID- 16575976
TI  - Mercury Derivatives of Aromatic Amines: I. Structure of Primary and Secondary p
      Amino-Phenylmercuric Compounds.

PMID- 16575977
TI  - Molecular Rearrangements of Triphenylmethane Derivatives: I. General Discussion.

PMID- 16575978
TI  - Molecular Rearrangements of Triphenylmethane Derivatives: II. Experimental Part.

PMID- 16575979
TI  - Ecology of the Murray Island Coral Reef.

PMID- 16575980
TI  - Changes in Shade, Color and Pattern in Fishes and their Bearing on Certain
      Problems of Behavior and Adaptation.

PMID- 16575981
TI  - Some Experiments on Spermatogenesis in Vitro.

PMID- 16575982
TI  - Growth and Variation in Maize.

PMID- 16575984
TI  - Chemical and Physiological Studies of a Man Fasting Thirtyone Days.

PMID- 16575983
TI  - On a New Group of Bactericidal Substances Obtained from Hexamethylenetetramine.

PMID- 16575985
TI  - The Study of Indian Music.

PMID- 16575986
TI  - Some Recent Anthropological Explorations.

PMID- 16575987
TI  - The Second Derivatives of the Extremal Integral for a General Class of Problems
      of the Calculus of Variations.

PMID- 16575988
TI  - Groups Possessing at Least One Set of Independent Generators Composed of as Many
      Operators as There are Prime Factors in the Order of the Group.

PMID- 16575989
TI  - Point Sets and Allied Cremona Groups.

PMID- 16575990
TI  - The Straight Lines on Modular Cubic Surfaces.

PMID- 16575991
TI  - The Diffusion of Horse Culture Among the North American Indians.

PMID- 16575992
TI  - Discovery of Algonkian Bacteria.

PMID- 16575993
TI  - Some Problems in Stellar Photometry.

PMID- 16575994
TI  - The Composition of Brachiopod Shells.

PMID- 16575995
TI  - On the Occurrence of the Line 4686A and the Related Series of Lines in the
      Spectra of the Planetary Nebulae.

PMID- 16575996
TI  - The Nature of Nerve Conduction in Cassiopea.

PMID- 16575997
TI  - A New Canonical Form of the Elliptic Integral.

PMID- 16575998
TI  - The Structure of Complex Atoms and the Changes of Mass and Weight Involved in
      Their Formation.

PMID- 16575999
TI  - Huntington's Chorea in Relation to Heredity and Eugenics.

PMID- 16576000
TI  - The Alcyonaria as a Factor in Reef Limestone Formation.

PMID- 16576001
TI  - Transformations of Conjugate Systems With Equal Invariants.

PMID- 16576003
TI  - Inheritance in the Asexual Reproduction of Hydra Viridis.

PMID- 16576002
TI  - On the Pole Effect in the Iron Arc.

PMID- 16576004
TI  - On the Monticellite-Like Mineral in Meteorites, and on Oldhamite as a Meteoric
      Constituent.

PMID- 16576006
TI  - Mitosis in Trichomonas.

PMID- 16576005
TI  - Absolute Scales of Photographic and Photovisual Magnitude.

PMID- 16576007
TI  - Confirmatory Experiments on the Value of the Solar Constant of Radiation.

PMID- 16576008
TI  - Variation of Flower Size in Nicotiana.

PMID- 16576009
TI  - Retention in the Circulation of Dextrose in Normal and Depancreatized Animals,
      and the Effect of an Intravenous Injection of an Emulsion of Pancreas Upon This
      Retention.

PMID- 16576010
TI  - Parthenocarpy and Parthenogenesis in Nicotiana.

PMID- 16576011
TI  - Exogamy and the Classificatory System of Relationship.

PMID- 16576012
TI  - Solution of an Infinite System of Differential Equations of the Analytic Type.

PMID- 16576013
TI  - Sex Ratio in Pigeons, Together with Observations on the Laying, Incubation and
      Hatching of the Eggs.

PMID- 16576014
TI  - Vividiffusion Experiments on the Ammonia of the Circulating Blood.

PMID- 16576015
TI  - 126 Parabolic Orbits of Meteor Streams.

PMID- 16576016
TI  - The Basil Silurian Formations of Eastern North America.

PMID- 16576017
TI  - A Method of Obtaining Complete Germination of Seeds in Oenothera and of Recording
      the Residue of Sterile Seed-Like Structures.

PMID- 16576018
TI  - The Osmotic Pressure of the Ions and of the Undissociated Molecules of Salts in
      Aqueous Solution.

PMID- 16576019
TI  - The Extension of the Spectrum Beyond the Schumann Region.

PMID- 16576020
TI  - Unsymmetrical Lines in Tube-Arc and Spark Spectra as an Evidence of a Displacing
      Action in These Sources.

PMID- 16576021
TI  - On the Factorization of Various Types of Expressions.

PMID- 16576022
TI  - The Direction of Rotation of Sun-Spot Vortices.

PMID- 16576023
TI  - Some Vortex Experiments Bearing on the Nature of Sun-Spots and Flocculi.

PMID- 16576024
TI  - Notices of Biographical Memoirs.

PMID- 16576026
TI  - A Singular Dark Marking on the Sky.

PMID- 16576025
TI  - Nova Geminorum No. 2 as a Wolf-Rayet Star.

PMID- 16576027
TI  - The Ruling and Performance of a Ten-Inch Diffraction Grating.

PMID- 16576028
TI  - A Highly Sensitive Electrometer.

PMID- 16576029
TI  - The Distribution and Functions of Tribal Societies Among the Plains Indians: A
      Preliminary Report.

PMID- 16576030
TI  - The Determination of Surface-Tension.

PMID- 16576031
TI  - An Exhibit in Physical Anthropology.

PMID- 16576032
TI  - The Compressibilities of the Elements and their Relations to Other Properties.

PMID- 16576033
TI  - Radial Velocities Within the Great Nebula of Orion.

PMID- 16576034
TI  - The Radial Velocities of the More Distant Stars.

PMID- 16576035
TI  - Localization of the Hereditary Material in the Germ Cells.

PMID- 16576036
TI  - Researches on the Chemical and Mineralogical Composition of Meteorites.

PMID- 16576037
TI  - On the Representation of Arbitrary Functions by Definite Integrals.

PMID- 16576038
TI  - The Lymphocyte as a Factor in Natural and Induced Resistance to Transplanted
      Cancer.

PMID- 16576039
TI  - Some Theorems Connected with Irrational Numbers.

PMID- 16576040
TI  - Weber's Law and Antagonistic Salt Action.

PMID- 16576041
TI  - The Polarized Fluorescence of Ammonium Uranyl Chloride.

PMID- 16576042
TI  - The Linguistic Classification of Potawatomi.

PMID- 16576043
TI  - The Light Curve of XX Cygni As a Contribution to the Study of Cepheid Variation.

PMID- 16576044
TI  - The Feebly Inhibited: III. Inheritance of Temperament; With Special Reference to
      Twins and Suicides.

PMID- 16576045
TI  - Second Type Stars of Low Mean Density.

PMID- 16576046
TI  - On the Pathological Action oe Arsenicals Upon the Adrenals.

PMID- 16576047
TI  - Variations in the Character and Distribution of the Renal Lesions Produced by
      Compounds of Arsenic.

PMID- 16576048
TI  - Seven Points on a Twisted Cubic Curve.

PMID- 16576049
TI  - The Indian and Nature.

PMID- 16576050
TI  - The Mechanism of Antagonistic Salt Action.

PMID- 16576051
TI  - The Nitrogen Problem in Arid Soils.

PMID- 16576052
TI  - A Notation for use in the Discussion of Star Colors.

PMID- 16576053
TI  - Distribution of Colors Among the Stars of N. G. C. 1647 and M 67.

PMID- 16576054
TI  - On Thiele's ;Phase' in Band Spectra.

PMID- 16576055
TI  - Why Polar Bodies Do Not Develop.

PMID- 16576056
TI  - Radial Velocities of the Planetary and Irregular Nebulae.

PMID- 16576057
TI  - The Octopus Motive in Ancient Chiriquian Art.

PMID- 16576058
TI  - The Life Cycle of Trypanosoma Brucei in the Rat and in Rat Plasma.

PMID- 16576060
TI  - On Isothermally Conjugate Nets of Space Curves.

PMID- 16576059
TI  - The Effect of Pressure on Polymorphic Transitions of Solids.

PMID- 16576061
TI  - The Role of the Liver in Acute Polycythaemia: the Mechanism Controlling the Red
      Corpuscle Content of the Blood.

PMID- 16576062
TI  - The Potentials at the Junctions of Salt Solutions.

PMID- 16576063
TI  - A Statistical Study of the Visual Double Stars in the Northern Sky.

PMID- 16576064
TI  - Walnut Mutant Investigations.

PMID- 16576065
TI  - Hereditary Fragility of Bone.

PMID- 16576067
TI  - A Mechanism of Protection Against Bacterial Infection.

PMID- 16576066
TI  - Experiments on the Development of the Limbs in Amphibia.

PMID- 16576068
TI  - On the Life-History of Giardia.

PMID- 16576069
TI  - The Inorganic Constituents of Alcyonaria.

PMID- 16576071
TI  - Notices of Biographical Memoirs.

PMID- 16576072
TI  - Salts, Soil-colloids, and Soils.

PMID- 16576070
TI  - An Experimental Analysis of the Origin and Relationship of Blood Corpuscles and
      the Lining Cells of Vessels.

PMID- 16576073
TI  - The Child and the Tribe.

PMID- 16576074
TI  - The Correlation of Potassium and Magnesium, Sodium and Iron, in Igneous Rocks.

PMID- 16576075
TI  - Theorem Concerning the Singular Points of Ordinary Linear Differential Equations.

PMID- 16576076
TI  - A Quantitative Study of Cutaneous Analgesia Produced by Various Opium Alkaloids.

PMID- 16576077
TI  - The Surface-Tension at the Interface Between Two Liquids.

PMID- 16576078
TI  - Outlines of a Proposed System of Classification of the Nebulae by Means of their
      Spectra.

PMID- 16576079
TI  - Some Probable Identities in Wave-Length in Nebular and Stellar Spectra.

PMID- 16576080
TI  - Energy Transformations during Horizontal Walking.

PMID- 16576081
TI  - The Physiology of the New-Born Infant.

PMID- 16576082
TI  - A Comparison of Methods for Determining the Respiratory Exchange of Man.

PMID- 16576083
TI  - Neuro-Muscular Effects of Moderate Doses of Alcohol.

PMID- 16576084
TI  - Variation and Inheritance in Abnormalities Occurring after Conjugation in
      Paramecium caudatum.

PMID- 16576085
TI  - The Influence of the Marginal Sense Organs on Functional Activity in Cassiopea
      xamachana.

PMID- 16576087
TI  - Hereditary Anchylosis of the Proximal Phalangeal Joints (Symphalangism).

PMID- 16576086
TI  - Heritable Variations and the Results of Selection in the Fission Rate of
      Stylonychia pustulata.

PMID- 16576088
TI  - The Relative Stimulating Efficiency of Spectral Colors for the Lower Organisms.

PMID- 16576089
TI  - The Mission Range, Montana.

PMID- 16576090
TI  - Definition of Limit in General Integral Analysis.

PMID- 16576091
TI  - Notice of Scientific Memoir.

PMID- 16576092
TI  - A Possible Origin for Some Spiral Nebulae.

PMID- 16576093
TI  - Studies of Magnitudes in Star Clusters: I. On the Absorption of Light in Space.

PMID- 16576094
TI  - Studies of Magnitudes in Star Clusters: II. On the Sequence of Spectral Types in
      Stellar Evolution.

PMID- 16576095
TI  - Experimental Evidence for the Essential Identity of the Selective and Normal
      Photo-Electric Effects.

PMID- 16576096
TI  - Concomitant Changes in Terrestrial Magnetism and Solar Radiation.

PMID- 16576097
TI  - Sub-Marine Solution of Limestone in Relation to the Murray-Agassiz Theory of
      Coral Atolls.

PMID- 16576098
TI  - The Archegonium and Sporophyte of Treubia Insignis Goebel.

PMID- 16576099
TI  - Brief Notes on Recent Anthropological Explorations Under the Auspices of the
      Smithsonian Institution and the U. S. National Museum.

PMID- 16576100
TI  - A Theory of Nerve-Conduction.

PMID- 16576101
TI  - Zuni Culture Sequences.

PMID- 16576102
TI  - The Numerical Results of Diverse Systems of Breeding.

PMID- 16576103
TI  - On the Effects of Feeding Pituitary Body (Anterior Lobe) Substance, and Corpus
      Luteum Substance to Growing Chicks.

PMID- 16576104
TI  - A Preliminary Report on Further Experiments in Inheritance and Determination of
      Sex.

PMID- 16576105
TI  - On the Degree of Inbreeding which Exists in American Jersey Cattle.

PMID- 16576106
TI  - Upper Limit of the Degree of Transitivity of a Substitution Group.

PMID- 16576107
TI  - The Extension of the Montana Phosphate Deposits Northward into Canada.

PMID- 16576108
TI  - A Peculiar Clay from near the City of Mexico.

PMID- 16576109
TI  - Cambrian Trilobites.

PMID- 16576110
TI  - The Minute Structure of the Solar Atmosphere.

PMID- 16576111
TI  - Monochromatic Photography of Jupiter and Saturn.

PMID- 16576112
TI  - Personal Equation and Steadiness of Judgment in the Estimation of the Number of
      Objects in Moderately Large Samples.

PMID- 16576114
TI  - Recent Explorations in the Cactus Deserts of South America.

PMID- 16576113
TI  - Polypeptide-Hydantoins.

PMID- 16576115
TI  - On the Albedo of the Planets and Their Satellites.

PMID- 16576116
TI  - Quantum Relations in Photo-Electric Phenomena.

PMID- 16576117
TI  - The Chemical Activity of the Ions of Hydrochloric Acid Determined by
      Electromotive Force Measurements.

PMID- 16576118
TI  - Effects of Centrifugal Force on the Polarity of the Eggs of Crepidula.

PMID- 16576119
TI  - The Emission Quanta of Characteristic X Rays.

PMID- 16576120
TI  - The Results of Investigations of the Ecology of the Floridian and Bahaman Shoal
      Water Corals.

PMID- 16576121
TI  - The Mechanics of Intrusion of the Black Hills (S. D.) Precambrian Granite.

PMID- 16576122
TI  - On the Fossil Algae of the Petroleum-Yielding Shales of the Green River Formation
      of Colorado and Utah.

PMID- 16576123
TI  - Archaeological Explorations at Pecos, New Mexico.

PMID- 16576124
TI  - Man and Metals.

PMID- 16576125
TI  - On the Observed Rotations of a Planetary Nebula.

PMID- 16576126
TI  - A Short Period Cepheid with Variable Spectrum.

PMID- 16576127
TI  - The Spectrum of delta Cephei.

PMID- 16576128
TI  - Investigations in Stellar Spectroscopy: I. A Quantitative Method of Classifying
      Stellar Spectra.

PMID- 16576129
TI  - Investigations in Stellar Spectroscopy: II. A Spectroscopic Method of Determining
      Stellar Parallaxes.

PMID- 16576130
TI  - Investigations in Stellar Spectroscopy: III. Application of a Spectroscopic
      Method of Determining Stellar Distances to Stars of Measured Parallax.

PMID- 16576131
TI  - Investigations in Stellar Spectroscopy: IV. Spectroscopic Evidence for the
      Existence of Two Classes of M Type Stars.

PMID- 16576132
TI  - The Failure and Revival of the Process of Pigmentation in the Human Skin.

PMID- 16576133
TI  - Banded Glacial Slates of Permo-carboniferous Age, Showing Possible Seasonal
      Variations in Deposition.

PMID- 16576134
TI  - An Extension of Feuerbach's Theorem.

PMID- 16576135
TI  - Deformations of Transformations of Ribaucour.

PMID- 16576137
TI  - The Age of the Middle Atlantic Coast Upper Cretaceous Deposits.

PMID- 16576136
TI  - Geographic History of the San Juan Mountains Since the Close of the Mesozoic Era.

PMID- 16576138
TI  - Upper Cretaceous Floras of the World.

PMID- 16576139
TI  - Observations on Ameba Feeding on Infusoria, and Their Bearing on the Surface
      Tension Theory.

PMID- 16576140
TI  - The Electromotive Force Produced by the Acceleration of Metals.

PMID- 16576142
TI  - On the Foundations of Plane Analysis Situs.

PMID- 16576141
TI  - The High Frequency Spectrum of Tungsten.

PMID- 16576143
TI  - A General Theory of Surfaces.

PMID- 16576145
TI  - Clift Islands in the Coral Seas.

PMID- 16576144
TI  - Dynamical Stability of Aeroplanes.

PMID- 16576146
TI  - On Some Relations Between the Proper Motions, Radial Velocities, and Magnitudes
      of Stars of Classes B and A.

PMID- 16576147
TI  - Asymmetry in the Proper Motions and Radial Velocities of Stars of Class B and
      Their Possible Relation to a Motion of Rotation.

PMID- 16576148
TI  - Theory of an Aeroplane Encountering Gusts.

PMID- 16576149
TI  - Terms of Relationship and Social Organization.

PMID- 16576150
TI  - Differential Equations and Implicit Functions in Infinitely Many Variables.

PMID- 16576151
TI  - The Sex of Parthenogenetic Frogs.

PMID- 16576152
TI  - De Vriesian Mutation in the Garden Bean, Phaseolus Vulgaris.

PMID- 16576153
TI  - Studies of Ductless Glands by the Electrical Method.

PMID- 16576154
TI  - The Distribution of the Chondriosomes to the Spermatozoa in Scorpions.

PMID- 16576156
TI  - Note on the Phosphorescence of Uranyl Salts.

PMID- 16576155
TI  - New Data on the Archaeology of Venezuela.

PMID- 16576157
TI  - The Pyranometer: An Instrument for Measuring Sky Radiation.

PMID- 16576158
TI  - Note on Lucas' Theorem.

PMID- 16576159
TI  - A Variable System of Sevens on Two Twisted Cubic Curves.

PMID- 16576160
TI  - The Neuromuscular Structure of Sea-Anemones.

PMID- 16576161
TI  - Change of the Ionization of Salts in Alcoholic Solvents with the Concentration.

PMID- 16576162
TI  - On The Mobilities of Gas Ions in High Electric Fields.

PMID- 16576163
TI  - The Relation of Myelin to the Loss of Water in the Mammalian Nervous System with
      Advancing Age.

PMID- 16576164
TI  - Differential Mitoses in the Germ-Cell Cycle of Dineutes Nigrior.

PMID- 16576165
TI  - Some Minerals from the Fluorite-Barite Vein Near Wagon Wheel Gap, Colorado.

PMID- 16576166
TI  - The Processes Taking Place in the Body by Which the Number of Erythrocytes Per
      Unit Volume of Blood is Increased in Acute Experimental Polycythaemia.

PMID- 16576167
TI  - The Influence of Morphin Upon the Elimination of Intravenously Injected Dextrose
      in Dogs.

PMID- 16576168
TI  - The Work of the American Meteor Society in 1914 and 1915.

PMID- 16576169
TI  - The Light Excitation by Slow Positive and Neutral Particles.

PMID- 16576170
TI  - An Apparent Dependence of the Apex and Velocity of Solar Motion, as Determined
      from Radial Velocities, Upon Proper Motion.

PMID- 16576171
TI  - Channeled Grating Spectra, Obtained in Successive Diffractions.

PMID- 16576172
TI  - The Effect of Parental Alcoholism (and Certain Other Drug Intoxications) Upon the
      Progeny in the Domestic Fowl.

PMID- 16576173
TI  - The Effectors of Sea-Anemones.

PMID- 16576174
TI  - Preliminary Evidence of Internal Motion in the Spiral Nebula Messier 101.

PMID- 16576176
TI  - The Responses of the Tentacles of Sea-Anemones.

PMID- 16576175
TI  - Nervous Transmission in Sea-Anemones.

PMID- 16576177
TI  - Preliminary Results on the Color of Nebulae.

PMID- 16576178
TI  - The Action of Alkali in the Production of Lipolytically Active Protein.

PMID- 16576179
TI  - The Excretion of Acids by Roots.

PMID- 16576180
TI  - Spectrographic Observations of Relative Motions in the Planetary Nebulae.

PMID- 16576181
TI  - New Determinations of Permeability.

PMID- 16576182
TI  - Point Sets and Cremona Groups: Part III.

PMID- 16576183
TI  - The Interferences of Spectra Both Reversed and Inverted.

PMID- 16576184
TI  - Sex Intergrades in a Species of Crustacea.

PMID- 16576185
TI  - Some Problems of Diophantine Approximation: A Remarkable Trigonometrical Series.

PMID- 16576187
TI  - Newton's Method in General Analysis.

PMID- 16576186
TI  - Steric Hindrance and the Existence of Odd Molecules (Free Radicals).

PMID- 16576188
TI  - The Cobaltammines.

PMID- 16576189
TI  - Organization of the Research Council.

PMID- 16576191
TI  - Non-Reversed Spectra of Restricted Coincidence.

PMID- 16576190
TI  - Path Differences Within Which Spectrum Interferences are Observable.

PMID- 16576192
TI  - The Equilibrium Between Acids and Bases in Sea Water.

PMID- 16576193
TI  - An Apparent Correspondence Between the Chemistry of Igneous Magmas and of Organic
      Metabolism.

PMID- 16576194
TI  - The Oaks of America.

PMID- 16576195
TI  - A Set of Independent Postulates for Cyclic Order.

PMID- 16576196
TI  - A New Method of Studying Ideational and Allied Forms of Behavior in Man and Other
      Animals.

PMID- 16576197
TI  - Electrical Conduction in Dilute Amalgams.

PMID- 16576198
TI  - Ideational Behavior of Monkeys and Apes.

PMID- 16576199
TI  - The Osmotic Pressure and Lowering of the Freezing-Point of Mixtures of Salts with
      One Another and with Non-Electrolytes in Aqueous Solutions.

PMID- 16576200
TI  - Certain General Properties of Functions.

PMID- 16576201
TI  - Sphenacodon Marsh, A Permocarboniferous Theromorph Reptile from New Mexico.

PMID- 16576203
TI  - The Condensation and Evaporation of Gas Molecules.

PMID- 16576202
TI  - On Volume in Biology.

PMID- 16576204
TI  - The Ninth Satellite of Jupiter.

PMID- 16576205
TI  - Aortic Cell Clusters in Vertebrate Embryos.

PMID- 16576206
TI  - Rheotropism of Epinephelus Striatus Bloch.

PMID- 16576207
TI  - Studies of the Genus Phytophthora.

PMID- 16576208
TI  - A Possible Function of the Ions in the Electric Conductivity of Metals.

PMID- 16576209
TI  - The Gravimetric Survey of the United States.

PMID- 16576210
TI  - The Magnetization of Iron, Nickel, and Cobalt by Rotation and the Nature of the
      Magnetic Molecule.

PMID- 16576211
TI  - The Intensities of X-Rays of the L Series.

PMID- 16576212
TI  - The Use of Vasectomized Male Mice as Indicators.

PMID- 16576213
TI  - Photographic Magnitudes of Stars in the Selected Areas of Kapteyn.

PMID- 16576214
TI  - Archaeology of Mammoth Cave and Vicinity: A Preliminary Report.

PMID- 16576215
TI  - The Production in Dogs of a Pathological Condition Which Closely Resembles Human
      Pellagra.

PMID- 16576216
TI  - The Complete Enumeration of Triad Systems in 15 Elements.

PMID- 16576218
TI  - The Reactions of the Melanophores of the Horned Toad.

PMID- 16576217
TI  - New Data on the Phosphorescence of Certain Sulphides: (Discussing Measurements by
      Drs. H. E. Howe, H. L. Howes and Percy Hodge).

PMID- 16576219
TI  - The Coordination of the Melanophore Reactions of the Horned Toad.

PMID- 16576220
TI  - Petrified Coals and Their Bearing on the Problem of the Origin of Coals.

PMID- 16576221
TI  - The Effect of Degree of Injury, Level of Cut and Time Within the Regenerative
      Cycle Upon the Rate of Regeneration.

PMID- 16576223
TI  - Research Committees in Educational Institutions.

PMID- 16576222
TI  - Preliminary Note on the Distribution of Stars With Respect to the Galactic Plane.

PMID- 16576224
TI  - Central Committee on Research.

PMID- 16576226
TI  - New Analyses of Echinoderms.

PMID- 16576225
TI  - The Stark Effect in Helium and Neon.

PMID- 16576227
TI  - On Utilizing the Facts of Juvenile Promise and Family History in Awarding Naval
      Commissions to Untried Men.

PMID- 16576228
TI  - The Triplet Series of Radium.

PMID- 16576229
TI  - The Measurement of Small Angles by Displacement Interferometry.

PMID- 16576230
TI  - Mechanisms that Defend the Body from Poliomyelitic Infection, (a) External or
      Extra-Nervous, (b) Internal or Nervous.

PMID- 16576231
TI  - The Behavior on Hydrolysis of the Simplest Secondary Nucleoside on Thymine.

PMID- 16576232
TI  - The Occurrence of Harmonics in the Infra-Red Absorption Spectra of Diatomic
      Gases.

PMID- 16576234
TI  - Daily Variation of Water and Dry Matter in the Leaves of Corn and the Sorghums.

PMID- 16576235
TI  - Note on Complementary Fresnellian Fringes.

PMID- 16576233
TI  - The Loss in Energy of Wehnelt Cathodes by Electron Emission.

PMID- 16576236
TI  - The Displacement Interferometry of Long Distances.

PMID- 16576237
TI  - The Cayleyan Curve of the Quartic.

PMID- 16576238
TI  - A Search for an Einstein Relativity-Gravitational Effect in the Sun.

PMID- 16576239
TI  - Triads of Transformations of Conjugate Systems of Curves.

PMID- 16576240
TI  - The Molecular Weights of the Triarylmethyls.

PMID- 16576241
TI  - Sex-Determination and Sex-Differentiation in Mammals.

PMID- 16576242
TI  - The Crystal Structure of Magnesium.

PMID- 16576243
TI  - The Structure of High-Standing Atolls.

PMID- 16576244
TI  - Studies of Magnitude in Star Clusters: VII. A Method for the Determination of the
      Relative Distances of Globular Clusters.

PMID- 16576245
TI  - The Principal Axes of Stellar Motion.

PMID- 16576246
TI  - Relation of Preferential Motion and of the Spectral-Class and Magnitude Velocity
      Progressions to Proper Motion.

PMID- 16576247
TI  - Growth of Isolated Sporophytes of Anthoceros.

PMID- 16576248
TI  - The Mesa Verde Types of Pueblos.

PMID- 16576249
TI  - A Determination of the Ratio of the Specific Heats of Hydrogen at 18 degrees and 
      190 degrees C.

PMID- 16576250
TI  - Note on the Coefficient of Total Radiation of a Uniformly Heated Enclosure.

PMID- 16576251
TI  - The Development of a Source for Standard Wavelengths and the Importance of their
      Fundamental Values.

PMID- 16576252
TI  - On the Presence of Albumoses in Extracts of the Posterior Lobe of the Hypophysis
      Cerebri.

PMID- 16576253
TI  - On the Role of the Thymus in the Production of Tetany.

PMID- 16576254
TI  - Evidence of Assortive Mating in a Nudibranch.

PMID- 16576255
TI  - Coral Reefs of Tutuila, with Reference to the Murray-Agassiz Solution Theory.

PMID- 16576256
TI  - Suggestions Relating to the New National Army by the Anthropology Committee of
      the National Research Council.

PMID- 16576257
TI  - Notices of Biographical Memoirs.

PMID- 16576258
TI  - A Necessary and Sufficient Condition for the Existence of a Stieltjes Integral.

PMID- 16576259
TI  - Transformations of Applicable Conjugate Nets of Curves on Surfaces.

PMID- 16576260
TI  - On Bilinear and N-Linear Functionals.

PMID- 16576261
TI  - The Crystal Structure of Chalcopyrite Determined by X Rays.

PMID- 16576262
TI  - The Isostatic Subsidence of Volcanic Islands.

PMID- 16576263
TI  - On the Deformation of an N-Cell.

PMID- 16576264
TI  - A Theorem on Series of Orthogonal Functions with an Application to Strum
      Liouville Series.

PMID- 16576265
TI  - Low-Temperature Formation of Alkaline Feldspars in Limestones.

PMID- 16576266
TI  - The Interferometry of Small Angles, etc. Methods by Direct and Reversed
      Superposed Spectra.

PMID- 16576268
TI  - Thermo-Electric Diagrams on the P-V-Plane.

PMID- 16576267
TI  - The Heat Capacity of Electro Positive Metals and the Thermal Energy of Free
      Electrons.

PMID- 16576269
TI  - A Determination of the Solar Motion and the Stream Motion Based on Radial
      Velocities and Absolute Magnitudes.

PMID- 16576270
TI  - Disease Resistance In Cabbage.

PMID- 16576271
TI  - Is a Moving Star Retarded by the Reaction of Its Own Radiation?

PMID- 16576272
TI  - On Electromagnetic Induction and Relative Motion: II.

PMID- 16576273
TI  - Notice of Biographical Memoirs.

PMID- 16576274
TI  - The Effect of Artificial Selection on Bristle Number in Drosophila ampelophila
      and its Interpretation.

PMID- 16576275
TI  - The Reactions of the Melanophores of Amiurus to Light and to Adrenalin.

PMID- 16576276
TI  - Further Experiments on the Sex of Parthenogenetic Frogs.

PMID- 16576277
TI  - The Resolving Powers of X-Ray Spectrometers and the Tungsten X-Ray Spectrum.

PMID- 16576279
TI  - Dependence of the Spectral Relation of Double Stars Upon Distance.

PMID- 16576278
TI  - Note on Methods of Observing Potential Differences Induced by the Earth's
      Magnetic Field in an Insulated Moving Wire.

PMID- 16576280
TI  - Hypothesis to Account for the Spectral Conditions of the Stars.

PMID- 16576281
TI  - Some Spectral Characteristics of Cepheid Variables.

PMID- 16576282
TI  - Types of Achromatic Fringes.

PMID- 16576283
TI  - Interference of Pencils Which Constitute the Remote Divergences from a Slit.

PMID- 16576284
TI  - A Study of the Motions of Forty-eight Double Stars.

PMID- 16576286
TI  - Invariants Which are Functions of Parameters of the Transformation.

PMID- 16576285
TI  - The Structure of an Electromagnetic Field.

PMID- 16576287
TI  - Effects of a Prolonged Reduction in Diet on 25 Men: I. Influence on Basal
      Metabolism and Nitrogen Excretion.

PMID- 16576288
TI  - Effects of a Prolonged Reduction in Diet on 25 Men: II. Bearing on Neuro-Muscular
      Processes and Mental Condition.

PMID- 16576289
TI  - Effects of a Prolonged Reduction in Diet on 25 Men: III. Influence on Efficiency
      During Muscular Work.

PMID- 16576291
TI  - The Study of the Sediments as an Aid to the Earth Historian.

PMID- 16576290
TI  - Possible Action of the Sex-Determining Mechanism.

PMID- 16576292
TI  - The Growth of the Alaskan Fur Seal Herd Between 1912 and 1917.

PMID- 16576293
TI  - The Destruction of Tetanus Antitoxin by Chemical Agents.

PMID- 16576295
TI  - Notes on Isotopic Lead.

PMID- 16576296
TI  - On the Representation of a Number as the Sum of any Number of Squares, and in
      Particular of five or seven.

PMID- 16576294
TI  - Tests for Fluorine and Tin in Meteorites with Notes on Maskelynite and the Effect
      of Dry Heat on Meteoric Stones.

PMID- 16576297
TI  - The Crystal Structure of Ice.

PMID- 16576298
TI  - Fringing Reefs of the Philippine Islands.

PMID- 16576299
TI  - Dilation of the Great Arteries Distal to Partially Occluding Bands.

PMID- 16576300
TI  - On the Correction of Optical Surfaces.

PMID- 16576301
TI  - Hereditary Tendency to Form Nerve Tumors.

PMID- 16576302
TI  - Arithmetical Theory of Certain Hurwitzian Continued Fractions.

PMID- 16576303
TI  - On Closed Curves Described by a Spherical Pendulum.

PMID- 16576304
TI  - The Taxonomic Position of the Genus Actinomyces.

PMID- 16576306
TI  - Glacial Depression and Post-Glacial Uplift of Northeastern America.

PMID- 16576305
TI  - Studies of Magnitudes in Star Clusters: VIII. A Summary of Results Bearing on the
      Structure of the Sidereal Universe.

PMID- 16576307
TI  - A Bacteriological Study of the Soil of Loggerhead Key, Tortugas, Florida.

PMID- 16576308
TI  - Autonomous Responses of the Labial Palps of Anodonta.

PMID- 16576309
TI  - The Depth of the Effective Plane in X-Ray Crystal Penetration.

PMID- 16576310
TI  - The Myodome and Trigemino-Facialis Chamber of Fishes and the Corresponding
      Cavities in Higher Vertebrates.

PMID- 16576311
TI  - The Effect of Inbreeding and Crossbreeding Upon Development.

PMID- 16576313
TI  - Measuring the Mental Strength of an Army.

PMID- 16576314
TI  - Invariants and Canonical Forms.

PMID- 16576312
TI  - Executive Order Issued by the President of the United States, May 11, 1918.

PMID- 16576315
TI  - Types of Phosphorescence.

PMID- 16576317
TI  - Maroon: A Recurrent Mutation in Drosophila.

PMID- 16576316
TI  - The Smithsonian ;Solar Constant' Expedition to Calama, Chile.

PMID- 16576318
TI  - The ;Homing Habits' of the Pulmonate Mollusk Onchidium.

PMID- 16576319
TI  - Growth and Duration of Life of Chiton Tuberculatus.

PMID- 16576321
TI  - The Interferometry of Vibrating Systems.

PMID- 16576320
TI  - Growth of Chiton Tuberculatus in Different Environments.

PMID- 16576322
TI  - On the Essence of Physical Relativity.

PMID- 16576324
TI  - The General Character of Specific Heats at High Temperatures.

PMID- 16576323
TI  - Gravitational Attraction in Connection with the Rectangular Interferometer.

PMID- 16576325
TI  - On Certain Projective Generalizations of Metric Theorems, and the Curves of
      Darboux and Segre.

PMID- 16576326
TI  - The Rectangular Interferometer with Achromatic Displacement Fringes in Connection
      with the Horizontal Pendulum.

PMID- 16576327
TI  - The Absorption Spectrum of the Novae.

PMID- 16576328
TI  - On Jacobi's Extension of the Continued Fraction Algorithm.

PMID- 16576329
TI  - A Character of Jordan Regions by Properties Having no Reference to Their
      Boundaries.

PMID- 16576330
TI  - A Biometric Study of Human Basal Metabolism.

PMID- 16576331
TI  - Sex and Sex Intergrades in Cladocera.

PMID- 16576333
TI  - The Phylogeny of the Acorn Barnacles.

PMID- 16576332
TI  - On the Method of Progression in Polyclads.

PMID- 16576334
TI  - Possible Derivation of the Lepadid Barnacles from the Phyllopods.

PMID- 16576335
TI  - Refractive Index and Solubilities of the Nitrates of Lead Isotopes.

PMID- 16576336
TI  - The Purification by Sublimation and the Analysis of Gallium Chloride.

PMID- 16576337
TI  - The Purification of Gallium by Electrolysis, and the Compressibility and Density
      of Gallium.

PMID- 16576338
TI  - The Growth-Rate of Samoan Coral Reefs.

PMID- 16576340
TI  - On Some Fundamentals of Pre-Cambrian Paleo-Geography.

PMID- 16576339
TI  - The Distances of Six Planetary Nebulae.

PMID- 16576341
TI  - The Ternary System CaO-MgO-SiO(2).

PMID- 16576342
TI  - Quantitative Relations Between Chromatin and Cytoplasm in the Genus Arcella, with
      their Relations to External Characters.

PMID- 16576343
TI  - A Theorem on Power Series, with an Application to Conformal Mapping.

PMID- 16576344
TI  - The Inorganic Constituents of Lobster Shells.

PMID- 16576345
TI  - Flagellate Affinities of Trichonympha.

PMID- 16576347
TI  - The Linkage System of Eight Sex-Linked Characters of Drosophila Virilis (Data of
      Metz).

PMID- 16576346
TI  - Is the Arrangement of the Genes in the Chromosome Linear?

PMID- 16576348
TI  - The Cause of Proliferation in Begonia Phyllomaniaca.

PMID- 16576349
TI  - The Percentage Number of Meteorite Falls and Finds Considered with Reference to
      Their Varying Basicity.

PMID- 16576350
TI  - Note on a Contact Lever, Using Achromatic Displacement Fingers.

PMID- 16576351
TI  - Interferential Contact Lever Experiments Relating to the Elastics of Small
      Bodies.

PMID- 16576352
TI  - Falklandia.

PMID- 16576354
TI  - Covariants of Binary Modular Groups.

PMID- 16576353
TI  - On the Real Folds of Abelian Varieties.

PMID- 16576355
TI  - The General Solution of the Indeterminate Equation: Ax + By + Cz +... = r.

PMID- 16576356
TI  - The Archaeology of the Southwest: A Preliminary Report.

PMID- 16576357
TI  - An Adjustment in Relation to the Fresnel Coefficient.

PMID- 16576358
TI  - Piebald Rats and the Theory of Genes.

PMID- 16576359
TI  - Bud Variation.

PMID- 16576360
TI  - The Growth Rate of an Annual Plant Helianthus.

PMID- 16576361
TI  - On Some Metallic Derivatives of Ethyl Thioglycollate.

PMID- 16576362
TI  - An Analysis of the Relation Between the Temperature and the Duration of a
      Biological Process.

PMID- 16576363
TI  - Restoration of Vitality Through Conjugation.

PMID- 16576364
TI  - Superposed or Duplicated Spectrum Fringes.

PMID- 16576366
TI  - Hydrogen Overvoltage.

PMID- 16576365
TI  - An Electromagnetic Hypothesis of the Kinetics of Heterogeneous Equilibrium, and
      of the Structure of Liquids.

PMID- 16576367
TI  - An Approximate Law of Energy Distribution in the General X-Ray Spectrum.

PMID- 16576368
TI  - Linear Arrangement of Genes and Double Crossing Over.

PMID- 16576369
TI  - The Spatial Relations of Genes.

PMID- 16576371
TI  - The Thermo-Electric Equation P = TdV/dT Once More.

PMID- 16576372
TI  - On the X-Ray Absorption Wave-Lengths of Lead Isotopes.

PMID- 16576373
TI  - Some Orienting Effects of Monochromatic Lights of Equal Intensities on Fucus
      Spores and Rhizoids.

PMID- 16576370
TI  - A Complete Apparatus for Absolute Acoustical Measurements.

PMID- 16576374
TI  - On the Most General Class L of Frechet in which the Heine-Borel-Lebesgue Theorem
      Holds True.

PMID- 16576375
TI  - An Electrodynamometer Using the Vibration Telescope.

PMID- 16576376
TI  - The Temperature of the Human Skin.

PMID- 16576377
TI  - On a Certain Class of Rational Ruled Surfaces.

PMID- 16576378
TI  - Evidence of Stream Motion Afforded by the Faint Stars Near the Orion Nebula.

PMID- 16576379
TI  - On the Use of the Spectroscopic Method for Determining the Parallaxes of the
      Brighter Stars.

PMID- 16576380
TI  - Relation of Color to Intrinsic Luminosity in Stars of the Same Spectral Type.

PMID- 16576381
TI  - The Motions in Space of Some Stars of High Radial Velocity.

PMID- 16576382
TI  - Deviations of the Sun's General Magnetic Field from That of a Uniformly
      Magnetized Sphere.

PMID- 16576383
TI  - On the Problem of the Production of Fat from Protein in the Dog.

PMID- 16576384
TI  - On the Twist in Conformed Mapping.

PMID- 16576385
TI  - Seventeen Skeletons of Moropus; Probable Habits of this Animal.

PMID- 16576386
TI  - The Structure of Atoms and the Octet Theory of Valence.

PMID- 16576387
TI  - A New Instrument for Measuring Pressures in a Gun.

PMID- 16576388
TI  - On the Angle of Repose of Wet Sand.

PMID- 16576389
TI  - Palaeomastodon, The Ancestors of the Long-Jawed Mastodons Only.

PMID- 16576390
TI  - The Elongation Due to Magnetization.

PMID- 16576391
TI  - Groups Involving Only Two Operators Which are Squares.

PMID- 16576392
TI  - Acoustical Impedance and the Theory of Horns and of the Phonograph.

PMID- 16576393
TI  - Phenomena of Cell Division in the Cambium of Arborescent Gymnosperms and Their
      Cytological Significance.

PMID- 16576394
TI  - On the Possible Form of the Equation of State of Powder Gases.

PMID- 16576396
TI  - Variations, Due to Heat Treatment, in the Rate of Adsorption of Air by Cocoanut
      Shell Charcoal.

PMID- 16576395
TI  - The Relative Adsorption of Mixtures of Oxygen and Nitrogen in Cocoanut Shell
      Charcoal.

PMID- 16576397
TI  - Real Hypersurfaces Contained in Abelian Varieties.

PMID- 16576398
TI  - Some Applications of the Variation of Hydrogen Overvoltage with the Pressure.

PMID- 16576400
TI  - The Interferometry of Rapid Vibrations Chiefly in Relation to Telephone Currents.

PMID- 16576399
TI  - The Effect of Transplanting Limbs upon the Formation of Nerve Plexuses and the
      Development of Peripheral Neurones.

PMID- 16576401
TI  - On the Pressure Variation of Specific Heat of Liquids.

PMID- 16576402
TI  - Studies of Magnitudes in Star Clusters: IX. The Distances and Distribution of
      Seventy Open Clusters.

PMID- 16576404
TI  - Radiation from a Moving Magneton.

PMID- 16576403
TI  - A Comparison of Certain Electrical Properties of Ordinary and Uranium Lead.

PMID- 16576405
TI  - On the Distribution of the Aphelia of the Secondary Bodies of the Solar System.

PMID- 16576406
TI  - Discoidal Structure of the Lithosphere.

PMID- 16576407
TI  - Recent Simultaneous Measurements of the Solar Constant of Radiation at Mount
      Wilson, California, and Calama, Chile.

PMID- 16576408
TI  - Rotating Projectiles from Smooth-Bore Guns.

PMID- 16576409
TI  - Means of Measuring the Speed of Projectiles in Flight.

PMID- 16576410
TI  - Some Problems of Sidereal Astronomy.

PMID- 16576411
TI  - On the Spectral Lines of a Pulsating Star.

PMID- 16576412
TI  - Ethylene Chlorhydrin.

PMID- 16576413
TI  - Studies of the Constitution of Steel.

PMID- 16576414
TI  - Inheritance of Quantity and Quality of Milk Production in Dairy Cattle.

PMID- 16576415
TI  - Studies of Magnitudes in Star Clusters: X. Spectral Type B and the Local Stellar
      System.

PMID- 16576417
TI  - Research Grants from Trust Funds of the Academy.

PMID- 16576416
TI  - Influence of Ions on the Electrification and Rate of Diffusion of Water Through
      Membranes.

PMID- 16576418
TI  - Award of Medals.

PMID- 16576419
TI  - The Influence of Degeneration of One Vagus Nerve upon the Development of
      Pneumonia.

PMID- 16576421
TI  - The Nervous Organization of a Nudibranch.

PMID- 16576420
TI  - On the Ethology of Chiton Tuberculatus.

PMID- 16576422
TI  - Are Genes Linear or Non-Linear in Arrangement?

PMID- 16576423
TI  - On Variation in Tartary Buckwheat, Fagopyrum Tataricum (L.) Gaertn.

PMID- 16576425
TI  - The Ozone Form of Hydrogen.

PMID- 16576424
TI  - The Effect of Milling on the Digestibility of Graham Flour.

PMID- 16576426
TI  - A Vapore-Free Vacuum Seal.

PMID- 16576427
TI  - The Change of Molecular Kinetic Energy into Molecular Potential Energy: The
      Entropy Principle and Molecular Association.

PMID- 16576428
TI  - The Displacement of the Gravitating Needle in its Dependence on Atmospheric
      Temperatures.

PMID- 16576429
TI  - Conditions Necessary and Sufficient for the Existence of a Stieltjes Integral.

PMID- 16576430
TI  - Transformations of Cyclic Systems of Circles.

PMID- 16576431
TI  - New Measurements of the Vapor Pressure of Mercury.

PMID- 16576432
TI  - Cohesion, Internal Pressure, Adhesion, Tensile Strength, Tensile Energy, Negative
      Surface Energy, and Molecular Attraction.

PMID- 16576433
TI  - The Adhesion Between Mercury, Water, and Organic Substances, and the Fundamental
      Principles of Flotation.

PMID- 16576434
TI  - A Benign Tumor that is Hereditary in Drosophila.

PMID- 16576435
TI  - Metallic Salts of Pyrrol, Indol, and Carbazol.

PMID- 16576436
TI  - Growth and Reproduction in Fowls in the Absence of Carotinoids and the
      Physiological Relation of Yellow Pigmentation to Egg Laying.

PMID- 16576437
TI  - Radiationless Orbits.

PMID- 16576438
TI  - The Effect Upon the Atom of the Passage of an Alpha Ray Through It.

PMID- 16576439
TI  - On the Embryological Basis of Human Mortality.

PMID- 16576440
TI  - An Example of Torsional Viscous Retrogression.

PMID- 16576441
TI  - The Nature and Function of the Antineuritic Vitamine.

PMID- 16576442
TI  - Reconstruction of the Skeleton of the Sauropod Dinosaur Camarasaurus Cope
      (Morosaurus Marsh).

PMID- 16576443
TI  - Restoration of Camarasaurus and Life Model.

PMID- 16576444
TI  - Plato's Atlantis in Palaeogeography.

PMID- 16576445
TI  - The Ionization and Activity of Largely Ionized Substances.

PMID- 16576446
TI  - The Commutativity of One-Parameter Transformations in Real Variables.

PMID- 16576447
TI  - The Intensities of X-Rays of the L Series: II. The Critical Potentials of the
      Platinum Lines.

PMID- 16576448
TI  - The Chemical Isolation of Vitamines.

PMID- 16576449
TI  - The Effect of Physical Agents on the Resistance of Mice to Cancer.

PMID- 16576450
TI  - The Protein Requirement of Maintenance in Man.

PMID- 16576451
TI  - A New Method of Determining the Solar Constant of Radiation.

PMID- 16576452
TI  - The Transplanting of Sea Anemones by Hermit Crabs.

PMID- 16576453
TI  - Spectra of Explosions.

PMID- 16576454
TI  - The Basal Metabolism of Boys from 1 to 13 Years of Age.

PMID- 16576455
TI  - An Apparent High Pressure Due to Adsorption, the Heat of Adsorption, and the
      Density of Gas-Mask Charcoals.

PMID- 16576456
TI  - Central American Calendars and the Gregorian Day.

PMID- 16576457
TI  - The Torsional Magnetic Energy Absorption of an Iron Conductor.

PMID- 16576459
TI  - A Study of Absorption Spectra with the Electric Furnace.

PMID- 16576458
TI  - The Adjustment to the Barometer of the Hematorespiratory Functions in Man.

PMID- 16576460
TI  - A Study of the Effect of a Magnetic Field on Electric Furnace Spectra.

PMID- 16576462
TI  - Groups Generated by Two Operators, s(1), s(2), Which Satisfy the Conditions s(1)
      = s(2), (s(1)s(2)) = I, s(1)s(2) = s(2)s(1).

PMID- 16576463
TI  - Model of the Linkage System of Eleven Second Chromosomegenes of Drosophila.

PMID- 16576464
TI  - The Development of Connective Tissue in the Amphibian Embryo.

PMID- 16576461
TI  - Selective Fertilization in Pollen Mixtures.

PMID- 16576465
TI  - Calcium and Magnesium Metabolism in Certain Diseases.

PMID- 16576467
TI  - On the Hyperplasia of Nerve Centers Resulting from Excessive Peripheral Loading.

PMID- 16576466
TI  - The Larger Opportunities for Research on the Relations of Solar and Terrestrial
      Radiation.

PMID- 16576468
TI  - Encephalitis and Poliomyelitis.

PMID- 16576469
TI  - A Statistical Method for Studying the Radiations from Radioactive Substances and
      the X-Rays and Its Application to some gamma-Ray Problems.

PMID- 16576470
TI  - On the Nature of the Heat Production in a System of Platinum Black, Alcohol and
      Air.

PMID- 16576471
TI  - Leptospira Icteroides and Yellow Fever.

PMID- 16576472
TI  - Human Retinal Adaptation.

PMID- 16576473
TI  - A Kinematical Interpretation of Electromagnetism.

PMID- 16576474
TI  - The Laws of Elastico-Viscous Flow: II.

PMID- 16576475
TI  - A Note on the Simple Device for Increasing a Photographic Power of Large
      Telescopes.

PMID- 16576476
TI  - Anthropometry of the Siouan Tribes.

PMID- 16576478
TI  - On the Mechanism of Fever Reduction by Drugs.

PMID- 16576479
TI  - Inferences from the Hypothesis of Dual Electric Conduction; the Thomson Effect.

PMID- 16576477
TI  - Transmission of Eye-Defects Induced in Rabbits by Means of Lens-Sensitized Fowl
      Serum.

PMID- 16576480
TI  - Note on Geometrical Products.

PMID- 16576482
TI  - The Evidence for the Linear Order of the Genes.

PMID- 16576481
TI  - Differentiation by Deformation.

PMID- 16576483
TI  - The Arrangement of Genes in Drosophila Virilis.

PMID- 16576484
TI  - The Functions of Intensity and Phase in the Binaural Location of Pure Tones.

PMID- 16576485
TI  - The Measurement of Small Time Intervals and Some Applications, Principally
      Ballistic.

PMID- 16576486
TI  - Charcoal Activation.

PMID- 16576488
TI  - A Thermodynamic Study of Electrolytic Solutions.

PMID- 16576487
TI  - The Starting of a Ship.

PMID- 16576489
TI  - The Formation of the Cell Plate in the Cambium of the Higher Plants.

PMID- 16576490
TI  - Functionals Invariant under One-Parameter Continuous Groups of Transformations in
      the Space of Continuous Functions.

PMID- 16576492
TI  - The Influence of Ions on the Osmotic Pressure of Solutions.

PMID- 16576491
TI  - Thermokinetics of Liometopum Apiculatum Mayr.

PMID- 16576493
TI  - Evidence on the Nature of Nuclear Activity.

PMID- 16576495
TI  - A Contribution of Genetics to the Practical Breeding of Dairy Cattle.

PMID- 16576494
TI  - A Study of the Persistence of Vision.

PMID- 16576496
TI  - On the Rate of Growth of the Population of the United States since 1790 and Its
      Mathematical Representation.

PMID- 16576497
TI  - On the Springfield Rifle and the Leduc Formula.

PMID- 16576498
TI  - Alkyl Amides of Isothiocyanacetic Acid.

PMID- 16576499
TI  - Studies of Magnitudes, in Star Clusters: XI. Frequency of Curves the Absolute
      Magnitude and Color Index for 1152 Giant Stars.

PMID- 16576500
TI  - On the Distortion in Conformal Mapping When the Second Coefficient in the Mapping
      Function Has an Assigned Value.

PMID- 16576502
TI  - Anomalous Osmose.

PMID- 16576503
TI  - A Photographic Method of Finding the Instantaneous Velocity of Sound Waves at
      Points Near the Source.

PMID- 16576504
TI  - Conformal Mapping of a Family of Real Conics on Another.

PMID- 16576505
TI  - Experiments on the Vibration of Air in Conical Horns.

PMID- 16576501
TI  - On the Connection of the Specific Heats with the Equation of State of a Gas.

PMID- 16576507
TI  - Fossil Plants from the Late Cretaceous of Tennessee.

PMID- 16576506
TI  - The Relative Importance of Heredity and Environment in Determining the Piebald
      Pattern of Guinea-Pigs.

PMID- 16576508
TI  - The Dynamics of a Fluctuating Growth Rate.

PMID- 16576509
TI  - Analytical Note on Certain Rhythmic Relations in Organic Systems.

PMID- 16576510
TI  - On the Class Number of the Field Omega(e/p) and the Second Case of Fermat's Last
      Theorem.

PMID- 16576511
TI  - Observations on the Sterility of Mutant Hybrids in Drosophila Virilis.

PMID- 16576512
TI  - Studies on the Transformation of the Intestinal Flora, with Special Reference to
      the Implantation of Bacillus Acidophilus: I. Feeding Experiments with Albino
      Rats.

PMID- 16576513
TI  - On a Single Numerical Index of the Age Distribution of a Population.

PMID- 16576515
TI  - The Influence of Cold in Stimulating the Growth of Plants.

PMID- 16576514
TI  - Upon an Important Method of Studying Problems of Relationship and of Geographical
      Distribution.

PMID- 16576516
TI  - On the Nature of the Negative Carriers Produced in Pure Hydrogen and Nitrogen by
      Photo-Electrons.

PMID- 16576517
TI  - Shock or Water Ram in Pipe Lines with Imperfect Reflection at the Discharge End
      and Including the Effects of Friction and Non-Uniform Change of Valve Opening.

PMID- 16576518
TI  - On Chondrules and Chondritic Structure in Meteorites.

PMID- 16576519
TI  - The Vertical Interferometer.

PMID- 16576520
TI  - On the Application of Interference Methods to Astronomical Measurements.

PMID- 16576521
TI  - A Modification of the Revolving Mirror Method for Measuring the Velocity of
      Light.

PMID- 16576523
TI  - Studies of Magnitude in Star Clusters: XII. Summary of a Photometric
      Investigation of the Globular System Messier 3.

PMID- 16576522
TI  - On the K Series of X-Rays.

PMID- 16576524
TI  - The Influence of Environment upon Development.

PMID- 16576525
TI  - The Possibilities of the Rocket in Weather Forecasting.

PMID- 16576526
TI  - Note on a Pneumatic Method of Measuring Variations of the Acceleration of
      Gravity.

PMID- 16576527
TI  - Note on Torsional Measurement of Variations of the Acceleration of Gravity by
      Interference Methods.

PMID- 16576528
TI  - The Genus Botrychium and Its Relationships.

PMID- 16576529
TI  - Further Measurements of the Effects of Pressure on Resistance.

PMID- 16576531
TI  - On the Relative Positions and Intensities of Lines in X-ray Spectra.

PMID- 16576530
TI  - Characteristic Absorption of X-rays: L. Series.

PMID- 16576532
TI  - On a Differential Equation Occurring in Page's Theory of Electromagnetism.

PMID- 16576533
TI  - A New Proof of a Theorem Due to Schoenflies.

PMID- 16576534
TI  - Are the Superior Cervical Ganlia Indispensable to the Maintenance of Life?

PMID- 16576535
TI  - Observations on the Body Temperature of Dry Cows.

PMID- 16576536
TI  - On the Structure of Finite Continuous Groups with Exceptional Transformations.

PMID- 16576537
TI  - Present Status of Geodesy and Some of the Problems of This Branch of Geophysics.

PMID- 16576538
TI  - The Problems of Seismology.

PMID- 16576539
TI  - The Status and Problems of Meteorology.

PMID- 16576540
TI  - Some of the Chief Problems in Terrestrial Magnetism and Electricity.

PMID- 16576541
TI  - The Problems and Functions of the Section of Physical Oceanography of the
      American Geophysical Union.

PMID- 16576542
TI  - The Problems of Volcanology.

PMID- 16576543
TI  - An Outline of Geophysical-Chemical Problems.

PMID- 16576544
TI  - The Ionization of Strong Electrolytes.

PMID- 16576545
TI  - On a Condition for Helmholtz's Equation Similar to Lame's.

PMID- 16576547
TI  - The Thomson Effect and Thermal Conduction in Metals.

PMID- 16576546
TI  - The Absorption of X-Rays by Chemical Elements of High Atomic Numbers.

PMID- 16576548
TI  - Motion on a Surface for any Positional Field of Force.

PMID- 16576549
TI  - Homologous Genes and Linear Linkage in Drosophila virilis.

PMID- 16576550
TI  - The Intensities of X-Rays of the L-Series: III. Critical Potentials of the
      Platinum and Tungsten Lines.

PMID- 16576551
TI  - Semivariants of a General System of Linear Homogeneous Differential Equations.

PMID- 16576552
TI  - Some New Methods in Interior Ballistics.

PMID- 16576553
TI  - The Mutant Crossveinless in Drosophila Melanogaster.

PMID- 16576554
TI  - Is Crossing Over a Function of Distance?

PMID- 16576555
TI  - Interspecific Hybrids in Crepis: I. Crepis capillaris (L) Wallr. x C. tectorum L.

PMID- 16576556
TI  - New Observations on the Variability of the Sun.

PMID- 16576557
TI  - The Permanent Gravitational Field in the Einstein Theory.

PMID- 16576558
TI  - A Simpeified Method for the Statistical Interpretation of Experimental Data.

PMID- 16576559
TI  - A Critical Study of Fertilizer Experiments.

PMID- 16576560
TI  - Preliminary Report on Pterergates in Pogonomyrmex Californicus.

PMID- 16576561
TI  - Hydrogen Ion Concentration of the Contents of the Small Intestine.

PMID- 16576563
TI  - Luminescence at High Temperatures.

PMID- 16576562
TI  - Blood Concentration Changes in Influenza.

PMID- 16576564
TI  - Functional Regulations in Animals with Composite Spinal Cords.

PMID- 16576565
TI  - Experiments with the Tube Resistance Furnace on the Effect of Potential
      Difference.

PMID- 16576566
TI  - An Application of the Porism of Four Tangents of a Twisted Cubic.

PMID- 16576567
TI  - Studies on the Transformation of the Intestinal Flora, with Special Reference to
      the Implantation of Bacillus Acidophilus: II. Feeding Experiments on Man.

PMID- 16576568
TI  - The Kilauea Volcano Observatory.

PMID- 16576569
TI  - Internal Motion in the Spiral Nebula Messier 33: Preliminary Results.

PMID- 16576570
TI  - The Basal Metabolism of Girls 12 to 17 Years of Age.

PMID- 16576571
TI  - On the Reflection and Re-emission of Electrons from Metal Surfaces: and a Method
      of Measuring the Ionizing Potential of Such Surfaces.

PMID- 16576572
TI  - Chronology of the San Juan Area.

PMID- 16576573
TI  - Some Geologic Conclusions from Geodetic Data.

PMID- 16576574
TI  - Experiments on the Electrical Conduction of a Hydrogen Alloy.

PMID- 16576576
TI  - The Present Status of the Long-Continued Pedigree Culture of Paramecium Aurelia
      at Yale University.

PMID- 16576575
TI  - The Vascular Anatomy of Normal and Variant Seedlings of Phaseolus vulgaris.

PMID- 16576577
TI  - The Attachment of Electrons to Neutral Molecules in Air.

PMID- 16576578
TI  - Peabody Museum Arizona Exploration, 1920.

PMID- 16576579
TI  - The Open Mercury Manometer Read by Displacement Interferometry.

PMID- 16576580
TI  - Studies on Catalysis: I. The Reduction of Uracil to Hydrouracil.

PMID- 16576581
TI  - The Application of a Differential Thermometer in Ebullioscopy.

PMID- 16576582
TI  - A Differential Thermometer.

PMID- 16576583
TI  - Normalized Geometric Systems.

PMID- 16576584
TI  - Problems of Potential Theory.

PMID- 16576585
TI  - Thermo-Electric Action and Thermal Conduction in Metals: A Summary.

PMID- 16576587
TI  - Novocaine as a Substitute for Curare.

PMID- 16576586
TI  - Quaternions and Their Generalizations.

PMID- 16576588
TI  - Note on a Method of Determining the Distribution of Pore Sizes in a Porous
      Material.

PMID- 16576589
TI  - An Apparent Case of Non-Mendelian Inheritance in Datura Due to a Disease.

PMID- 16576590
TI  - The Effect of a Variation in Milling on the Digestibility of Wheat Flours.

PMID- 16576591
TI  - The Mathematical Theory of the Apportionment of Representatives.

PMID- 16576592
TI  - Current Maps of the Location of the Mutant Genes of Drosophila Melanogaster.

PMID- 16576593
TI  - Some Physical Characteristics of the Ear.

PMID- 16576594
TI  - Non-Disjunction and the Chromosome Relationships of Drosophila willistoni.

PMID- 16576595
TI  - An Apparatus for Determination of the Gases in Blood and Other Solutions.

PMID- 16576596
TI  - Adaptive Radiation and Classification of the Proboscidea.

PMID- 16576597
TI  - A Case of Rearrangement of Genes in Drosophila.

PMID- 16576598
TI  - A Remeasurement of the Radiation Constant, h, by Means of X-Rays.

PMID- 16576599
TI  - The U-Tube Absolute Electrometer.

PMID- 16576600
TI  - Geometric Aspects of the Abelian Modular Functions of Genus Four (I).

PMID- 16576601
TI  - Melanovanadite, A New Mineral from Mina Ragra, Pasco, Peru.

PMID- 16576602
TI  - The Average of an Analytic Functional.

PMID- 16576603
TI  - On the Calculation of the X-Ray Absorption Frequencies of the Chemical Elements.

PMID- 16576604
TI  - On the Calculation of the X-Ray Absorption Frequencies of the Chemical Elements
      (Second Note).

PMID- 16576605
TI  - Semi-covariants of a General System of Linear Homogeneous Differential Equations.

PMID- 16576606
TI  - An Algorism for Differential Invariant Theory.

PMID- 16576607
TI  - The Effect of Temperature and of the Concentration of Hydrogen Ions upon the Rate
      of Destruction of Antiscorbutic Vitamin (Vitamin C).

PMID- 16576608
TI  - The Evaluation of Quantum Integrals.

PMID- 16576609
TI  - The Further Extension of the Ultra-violet Spectrum and the Progression with
      Atomic Number of the Spectra of Light Elements.

PMID- 16576610
TI  - The Average of an Analytic Functional and the Brownian Movement.

PMID- 16576611
TI  - Measurements of the Deviation from Ohm's Law in Metals at High Current Densities.

PMID- 16576612
TI  - An Integral Equality and its Applications.

PMID- 16576613
TI  - The Mobilities of Electrons.

PMID- 16576614
TI  - A Method for Obtaining Constants for Formulas of Organic Growth.

PMID- 16576615
TI  - On the Approximate Solutions in Integers of a Set of Linear Equations.

PMID- 16576616
TI  - A Physical Basis for Epidemiology.

PMID- 16576617
TI  - On the Relation of a Continuous Curve to Its Complementary Domains in Space of
      Three Dimensions.

PMID- 16576618
TI  - Characteristic Effects upon Growth, Oestrus and Ovulation Induced by the
      Intraperitoneal Administration of Fresh Anterior Hypophyseal Substance.

PMID- 16576619
TI  - A Study of the Effects of Cucurbita Pepo Seeds on Kidney Excretion.

PMID- 16576621
TI  - Absorption of Short X-Rays by Aluminium and Copper.

PMID- 16576620
TI  - The Action of Diazomethane on Uracil.

PMID- 16576622
TI  - The Effective Temperature of 16 Stars as Estimated from the Energy Distribution
      in the Complete Spectrum.

PMID- 16576623
TI  - Additional Studies in Arrested Evolution.

PMID- 16576624
TI  - New Forms of Life from the Silurian.

PMID- 16576625
TI  - The Oxidation of Hydroquinol in the Presence of Aliphatic Amines.

PMID- 16576626
TI  - The Grating Space of Mica and the Intensities of the Spectral Orders.

PMID- 16576627
TI  - Ionization and Radiation Potentials and the Size of the Atom.

PMID- 16576629
TI  - Plane Reflection of Sound, as Exhibited by the Pinhole Resonator.

PMID- 16576628
TI  - Periods and Logarithmic Decrement of the Gravitation Needle under High
      Exhaustion.

PMID- 16576630
TI  - Note on the Problem of Great Stellar Distances.

PMID- 16576631
TI  - The Vital Index of the Population of England and Wales, 1838-1920.

PMID- 16576633
TI  - A Solution of the Linear Matrix Equation by Double Multiplication.

PMID- 16576632
TI  - Seasonal Fluctuations of the Vital Index of a Population.

PMID- 16576634
TI  - Cylindrical Distribution of Nodal Strength around the Pipe Normal.

PMID- 16576635
TI  - Ionization and Absorption Effects in the Electric Furnace.

PMID- 16576637
TI  - The Effect of Ether upon the Migration of the Scale Pigment and the Retinal
      Pigment in the Fish, Fundulus Heteroclitus.

PMID- 16576636
TI  - Preliminary Note on a Biometrical Study of the Relations of Certain Viscera in
      Tuberculosis.

PMID- 16576638
TI  - The Diverse Effects of Adrenalin upon the Migration of the Scale Pigment and the
      Retinal Pigment in the Fish, Fundulus Heteroclitus, Linn.

PMID- 16576639
TI  - A Side Line in the Importation of Insect Parasites of Injurious Insects from one
      Country to Another.

PMID- 16576640
TI  - On the Location of the Roots of the Derivative of a Polynomial.

PMID- 16576641
TI  - On the Distribution of the Velocities of Stars of Late Types of Spectrum.

PMID- 16576642
TI  - Contribution to the Energetics of Evolution.

PMID- 16576643
TI  - Natural Selection as a Physical Principle.

PMID- 16576644
TI  - Bactericidal Properties of the Products of Radium Emanation.

PMID- 16576645
TI  - The Jades of Middle America.

PMID- 16576646
TI  - On a Comparison of the Relative Sensitiveness of Telephones.

PMID- 16576647
TI  - The Equilibrium Positions of the Vacuum Gravitation Needle in 1921 and 1922.

PMID- 16576649
TI  - Proof of a Theorem Due to Heaviside.

PMID- 16576650
TI  - The Stability of the Normal Age Distribution.

PMID- 16576648
TI  - Further Measurements of Stellar Temperatures and Planetary Radiation.

PMID- 16576651
TI  - Projective and Affine Geometry of Paths.

PMID- 16576652
TI  - A Direct Method of Testing Color Vision in Lower Animals.

PMID- 16576653
TI  - Characteristics of a Short Wave Oscillator at Very Low Pressures.

PMID- 16576654
TI  - The Refraction of X-Rays in Calcite.

PMID- 16576655
TI  - The Compressibility of Metals at High Pressures.

PMID- 16576656
TI  - A Further Note on the Mathematical Theory of Population Growth.

PMID- 16576657
TI  - On the Hypothesis of Constant Atomic Radii.

PMID- 16576658
TI  - Photographic Determination of Parallaxes with the 100-Inch Reflector.

PMID- 16576659
TI  - Light and Color Variations of Nova Aquilae 1918.4.

PMID- 16576660
TI  - A Theory of the Hall Effect and the Related Effect for Several Metals.

PMID- 16576661
TI  - Studies of Subspecific Hybrids in Peromyscus.

PMID- 16576663
TI  - Leucocytic Secretions.

PMID- 16576662
TI  - Sets of Conjugate Cycles of a Substitution Group.

PMID- 16576664
TI  - Drowned Coral Reefs South of Japan.

PMID- 16576665
TI  - A Note on the Statistics of Cyclic Growth.

PMID- 16576666
TI  - Stokes' Law of Fall Completely Corrected.

PMID- 16576667
TI  - Gaseous Viscosity Measured by the Interferometer U-Tube.

PMID- 16576668
TI  - Compressibility, Internal Pressure and Atomic Magnitudes.

PMID- 16576669
TI  - The Separation of Isotopes.

PMID- 16576671
TI  - An Investigation of the Chemical Nature of Two Typical Enzymes: Pancreatic and
      Malt Amylases.

PMID- 16576670
TI  - The Mechanism of Selective Bacteriostasis.

PMID- 16576672
TI  - Note on the Relative Abundance of the Elements in the Earth's Crust.

PMID- 16576673
TI  - Continuous Transformations of Manifolds.

PMID- 16576674
TI  - A Lemma on Systems of Knotted Curves.

PMID- 16576675
TI  - The Nerve Net in the Earthworm: Preliminary Report.

PMID- 16576676
TI  - Concerning the Cut-Points of Continuous Curves and of Other Closed and Connected
      Point-sets.

PMID- 16576677
TI  - The Reduction Division in Haploid, Diploid, Triploid and Tetraploid Daturas.

PMID- 16576679
TI  - The Significance of the Experimentally Determined Crystal Structures of the
      Alkali Polyhalides.

PMID- 16576678
TI  - The Variation and Inheritance of Milk Characters.

PMID- 16576680
TI  - The Critical and Dissociation Potentials of Hydrogen.

PMID- 16576681
TI  - The Reflection by a Crystal of X-Rays Characteristic of Chemical Elements in It.

PMID- 16576682
TI  - On the Abnormal Reflection of X-Rays by Crystals.

PMID- 16576683
TI  - Electric Conduction: Hall's Theory and Perkins' Phenomenon.

PMID- 16576684
TI  - Crossing-Over and the Theory That the Genes Are Arranged in the Chromosomes in
      Serial Order.

PMID- 16576685
TI  - Some Consequences of Different Extents of Interference, in the Crossing-Over of
      the Genes.

PMID- 16576686
TI  - Genetic Variation in Linkage Values.

PMID- 16576688
TI  - The Transfer in Quanta of Radiation Momentum to Matter.

PMID- 16576689
TI  - Mutual Electromagnetic Momentum and Energy of a System of Moving Charges.

PMID- 16576687
TI  - The Displacements of the Capillary Electrometer, for Progressive Dilutions of the
      Electrolyte.

PMID- 16576690
TI  - Further Experiments on the Mass of the Electric Carrier in Metals.

PMID- 16576691
TI  - Removal of the Block to Self-Fertilization in the Ascidian Ciona.

PMID- 16576692
TI  - On Riemann Spaces Conformal to Einstein Spaces.

PMID- 16576693
TI  - Another Interpretation of the Fundamental Gaugevector of Weyl's Theory of
      Relativity.

PMID- 16576694
TI  - Tensor Analysis Without Coordinates.

PMID- 16576696
TI  - On Irregularities in the Velocity Curves of Spectroscopic Binaries.

PMID- 16576695
TI  - Geometric Aspects of the Abelian Modular Functions of Genus Four (III).

PMID- 16576697
TI  - On the Form of the Distribution Law of Stellar Velocities.

PMID- 16576698
TI  - The Solar Prelude of an Unusual Winter.

PMID- 16576699
TI  - The Stratified Subsidence of Fine Particles.

PMID- 16576701
TI  - The Quasi Equation P = TdV/dT.

PMID- 16576700
TI  - Theory of the Settling of Fine Particles.

PMID- 16576702
TI  - Joining the Infra-red and Electric Wave Spectra.

PMID- 16576704
TI  - Some Recent Measurements of Trans-Atlantic Radio Transmission.

PMID- 16576703
TI  - On the Constant Ratio of Mean-to-mid Potential or Current at Successive
      Equidistant Points Along a Uniform Electric Conducting Line, Real or Artificial,
      in the Steady State.

PMID- 16576705
TI  - Body Build and its Inheritance.

PMID- 16576706
TI  - A Bohr-Langmuir Transformation.

PMID- 16576707
TI  - Form of the Number of the Subgroups of a Prime Power Group.

PMID- 16576708
TI  - The Interference of Light and the Quantum Theory.

PMID- 16576709
TI  - Note on the Width of Spectral Lines Due to Collisions and Quantum Theory.

PMID- 16576711
TI  - Notes on Germanium Oxide.

PMID- 16576710
TI  - Change in Wave-length by Scattering.

PMID- 16576712
TI  - The Correlation of Respiratory and Circulatory Data for Adult Males.

PMID- 16576713
TI  - Studies of the Larger Tertiary Foraminifera from Tropical and Subtropical
      America.

PMID- 16576715
TI  - The Vibration of Air in Tubes Capped at Both Ends.

PMID- 16576714
TI  - Mechanics of Locomotion in Amoeba.

PMID- 16576716
TI  - The Vibration of the Air Filament in Quill Tubes Capped at Both Ends.

PMID- 16576717
TI  - Correlation between Physical and Medical Findings on Normal Ears.

PMID- 16576719
TI  - The Root System of Epigaea Repens and its Relation to the Fungi of the Humus.

PMID- 16576718
TI  - The Einstein Equations of the Gravitational Field for an Arbitrary Distribution
      of Matter.

PMID- 16576720
TI  - The Symmetry of the Internal Ears in Flatfishes.

PMID- 16576721
TI  - Motion of an Electric Particle in a Riemann Space.

PMID- 16576722
TI  - The Marginal Belts of the Coral Seas.

PMID- 16576723
TI  - The Depth of Coral-Reef Lagoons.

PMID- 16576724
TI  - A Theory of Color Production: I.

PMID- 16576725
TI  - A Theory of Color Production: II, Inorganic Compounds.

PMID- 16576727
TI  - On the Mean Absolute Magnitudes of the K and M Giants and the Systematic Errors
      in Trigonometric Parallaxes.

PMID- 16576728
TI  - Measurements on the Expression of Emotion in Music.

PMID- 16576726
TI  - The Asymmetry in the Distribution of Stellar Velocities.

PMID- 16576730
TI  - The Motion of a Falling Chronograph Projectile.

PMID- 16576729
TI  - Groups of Order 2 in Which the Number of the Sub-Groups of at Least One Order Is
      of the Form 1 + 4k.

PMID- 16576731
TI  - The Mobilities of Electrons in Air.

PMID- 16576732
TI  - The Thermal Conductivity of Liquids.

PMID- 16576734
TI  - Revised Magnitudes and Color Indices of the Planets.

PMID- 16576733
TI  - Photovisual Magnitudes of One Hundred Bright Stars.

PMID- 16576735
TI  - The Origin of Secretory Granules.

PMID- 16576736
TI  - The Heredity of Microscopic Hair Characters in Peromyscus.

PMID- 16576737
TI  - Preliminary Note: On the Variations of the Sun's Visible Features Associated with
      Variations of Solar Radiation.

PMID- 16576738
TI  - The Quantum Integral and Diffraction by a Crystal.

PMID- 16576739
TI  - The Principle of Minimum Energy and the Motion of Fluids.

PMID- 16576740
TI  - The Volume Changes of Five Gases under High Pressures.

PMID- 16576741
TI  - Achromatic and Superchromatic Fringes with a Calcite Rhomb.

PMID- 16576742
TI  - Vibration of the Air Filament in Quill Tubes: Single Telephonic Exciter.

PMID- 16576743
TI  - Preliminary Attempt to Measure Gravimetrically the Distance-Effect of Chemical
      Affinity.

PMID- 16576744
TI  - The Effects of Cutting the Giant Fibers in the Earthworm, Eisenia Foetida (Sav.).

PMID- 16576745
TI  - On the Relative Velocity of Blue and Yellow Light.

PMID- 16576746
TI  - Size-Factors and Size-Inheritance.

PMID- 16576747
TI  - A Generalization of Volterra's Derivative.

PMID- 16576748
TI  - Retraction.

PMID- 16576749
TI  - Optimally sparse representation in general (nonorthogonal) dictionaries via l
      minimization.
AB  - Given a dictionary D = {d(k)} of vectors d(k), we seek to represent a signal S as
      a linear combination S = summation operator(k) gamma(k)d(k), with scalar
      coefficients gamma(k). In particular, we aim for the sparsest representation
      possible. In general, this requires a combinatorial optimization process.
      Previous work considered the special case where D is an overcomplete system
      consisting of exactly two orthobases and has shown that, under a condition of
      mutual incoherence of the two bases, and assuming that S has a sufficiently
      sparse representation, this representation is unique and can be found by solving
      a convex optimization problem: specifically, minimizing the l(1) norm of the
      coefficients gamma. In this article, we obtain parallel results in a more general
      setting, where the dictionary D can arise from two or several bases, frames, or
      even less structured systems. We sketch three applications: separating linear
      features from planar ones in 3D data, noncooperative multiuser encoding, and
      identification of over-complete independent component models.

PMID- 16576751
TI  - PNAS at volume 100.

PMID- 16576750
TI  - Controlling market power and price spikes in electricity networks: Demand-side
      bidding.
AB  - In this article we report an experiment that examines how demand-side bidding can
      discipline generators in a market for electric power. First we develop a
      treatment without demand-side bidding; two large firms are allocated baseload and
      intermediate cost generators such that either firm might unilaterally withhold
      the capacity of its intermediate cost generators from the market to benefit from
      the supracompetitive prices that would result from only selling its baseload
      units. In a converse treatment, ownership of some of the intermediate cost
      generators is transferred from each of these firms to two other firms such that
      no one firm could unilaterally restrict output to spawn supracompetitive prices.
      Having established a well controlled data set with price spikes paralleling those
      observed in the naturally occurring economy, we also extend the design to include
      demand-side bidding. We find that demand-side bidding completely neutralizes the
      exercise of market power and eliminates price spikes even in the presence of
      structural market power.

PMID- 16576753
TI  - Hessian eigenmaps: locally linear embedding techniques for high-dimensional data.
AB  - We describe a method for recovering the underlying parametrization of scattered
      data (m(i)) lying on a manifold M embedded in high-dimensional Euclidean space.
      The method, Hessian-based locally linear embedding, derives from a conceptual
      framework of local isometry in which the manifold M, viewed as a Riemannian
      submanifold of the ambient Euclidean Space R(n), is locally isometric to an open,
      connected subset Theta of Euclidean space R(d). Because Theta does not have to be
      convex, this framework is able to handle a significantly wider class of
      situations than the original ISOMAP algorithm. The theoretical framework revolves
      around a quadratic form H(f) = ?(M)||H(f)(m)||2(F)dm defined on functions f: M-->
      R. Here Hf denotes the Hessian of f, and H(f) averages the Frobenius norm of the
      Hessian over M. To define the Hessian, we use orthogonal coordinates on the
      tangent planes of M. The key observation is that, if M truly is locally isometric
      to an open, connected subset of R(d), then H(f) has a (d + 1)-dimensional null
      space consisting of the constant functions and a d-dimensional space of functions
      spanned by the original isometric coordinates. Hence, the isometric coordinates
      can be recovered up to a linear isometry. Our method may be viewed as a
      modification of locally linear embedding and our theoretical framework as a
      modification of the Laplacian eigenmaps framework, where we substitute a
      quadratic form based on the Hessian in place of one based on the Laplacian.

PMID- 16576752
TI  - The independence of our genome assemblies.

PMID- 16576754
TI  - Scaling behavior of random knots.
AB  - Using numerical simulations we investigate how overall dimensions of random knots
      scale with their length. We demonstrate that when closed non-self-avoiding random
      trajectories are divided into groups consisting of individual knot types, then
      each such group shows the scaling exponent of approximately 0.588 that is typical
      for self-avoiding walks. However, when all generated knots are grouped together,
      their scaling exponent becomes equal to 0.5 (as in non-self-avoiding random
      walks). We explain here this apparent paradox. We introduce the notion of the
      equilibrium length of individual types of knots and show its correlation with the
      length of ideal geometric representations of knots. We also demonstrate that
      overall dimensions of random knots with a given chain length follow the same
      order as dimensions of ideal geometric representations of knots.

PMID- 16576755
TI  - Molecular genetics and evolution of pheromone biosynthesis in Lepidoptera.
AB  - A GREAT DIVERSITY OF PHEROMONE STRUCTURES ARE USED BY MOTH SPECIES (INSECTA:
      Lepidoptera) for long-distance mating signals. The signal/response channel seems
      to be narrow for each species, and a major conundrum is how signal divergence has
      occurred in the face of strong selection pressures against small changes in the
      signal. Observations of various closely related and morphologically similar
      species that use pheromone components biosynthesized by different enzymes and
      biosynthetic routes underscore the question as to how major jumps in the
      biosynthetic routes could have evolved with a mate recognition system that is
      based on responses to a specific blend of chemicals. Research on the desaturases
      used in the pheromone biosynthetic pathway for various moth species has revealed
      that one way to make a major shift in the pheromone blend is by activation of a
      different desaturase from mRNA that already exists in the pheromone gland. Data
      will be presented to support the hypothesis that this process was used in the
      evolution of the Asian corn borer, Ostrinia furnacalis species. In that context,
      moth sex-pheromone desaturase genes seem to be evolving under a birth-and-death
      process. According to this model of multigene family evolution, some genes are
      maintained in the genome for long periods of time, whereas others become deleted
      or lose their functionality, and new genes are created through gene duplication.
      This mode of evolution seems to play a role in moth speciation, as exemplified by
      the case of the Asian corn borer and European corn borer, Ostrinia nubilalis
      species.

PMID- 16576756
TI  - PNAS goes weekly in the new year.

PMID- 16576757
TI  - Biography of june B. Nasrallah.

PMID- 16576758
TI  - An open access option for PNAS.

PMID- 16576759
TI  - Responsible authorship of papers in PNAS.

PMID- 16576761
TI  - Lower open access fees and institutional partnerships.

PMID- 16576760
TI  - The art and science of constructing the molecules of nature.

PMID- 16576762
TI  - Formation and structure of ramified charge transportation networks in an
      electromechanical system.
AB  - We present findings in an experiment where we obtain stationary ramified
      transportation networks in a macroscopic nonbiological system. Our purpose here
      is to introduce the phenomenology of the experiment. We describe the dynamical
      formation of the network which consists of three growth stages: (I) strand
      formation, (II) boundary formation, and (III) geometric expansion. We find that
      the system forms statistically robust network features, like the number of
      termini and the number of branch points. We also find that the networks are
      usually trees, meaning that they lack closed loops; indeed, we find that loops
      are unstable in the network. Finally, we find that the final topology of the
      network is sensitive to the initial conditions of the particles, in particular to
      its geometry.

PMID- 16576763
TI  - Commensurability and stability in nonperiodic systems.
AB  - We have investigated the response of 3D Bi(2)Sr(2)CaCu(2)O(8) vortex structures
      to a weak perturbation induced by 2D Fe pinning structures acting on one
      extremity of vortex lines. The pinning patterns were nano-engineered at the
      sample surface by means of either a Bitter decoration of the vortex lattice or
      electron-beam lithography. The commensurability conditions between 2D rigid
      pinning potentials and 3D elastic structures with short-range positional and long
      range orientational correlation have been experimentally determined. When the 2D
      potential is a replica of the nonperiodic vortex structure an amplification of
      its interaction with the vortex structure takes place. This effect is detected
      only for the first matching field, becoming negligible for other matching fields.
      On the other hand, a periodic 2D perturbation is shown to transform the
      nonperiodic Bragg glass-like structure into an Abrikosov crystal with an
      effective Debye-Waller factor.

PMID- 16576766
TI  - How and why to publish in PNAS.

PMID- 16576768
TI  - Vibration in Spark-Blown Closed Quill Tubes: Electric Oscillation.

PMID- 16576769
TI  - Remarks on a Point Set Constructed by Antoine.

PMID- 16576767
TI  - PNAS Profiles: How do Academy members get started in science?

PMID- 16576770
TI  - A Study of the Interaction of Host and Parasite: A Reaction Product in Infections
      with Trypanosoma Lewisi which Inhibits the Reproduction of the Trypanosomes.

PMID- 16576771
TI  - Retarded Establishment of Introduced Parasites of Injurious Insects.

PMID- 16576773
TI  - Discoveries during the Season of 1923 by the Third Asiatic Expedition in
      Mongolia.

PMID- 16576772
TI  - Does the Inheritance of Differences in General Size Depend upon General or
      Special Size Factors?

PMID- 16576775
TI  - Note on Electrically Exploded Wires in High Vacuum.

PMID- 16576774
TI  - Spectra of Meteor Trains.

PMID- 16576776
TI  - On Tertiary X-Radiation, Etc.

PMID- 16576777
TI  - Further Experiments upon the Reflection by a Crystal of Its Characteristic X
      Radiation.

PMID- 16576778
TI  - The Law of Sun-Spot Polarity.

PMID- 16576779
TI  - On the Subdivision of 3-Space by a Polyhedron.

PMID- 16576780
TI  - An Example of a Simply Connected Surface Bounding a Region which is not Simply
      Connected.

PMID- 16576781
TI  - The Scattering of X-Rays and Bragg's Law.

PMID- 16576782
TI  - Refraction of X-Rays in Pyrites.

PMID- 16576783
TI  - The Effects of Replacing the Cephalic End of the Embryonic Spinal Cord by an
      Extraneous Medulla in Amblystoma.

PMID- 16576784
TI  - Some Unexpected Results of the Heteroplastic Transplantation of Limbs.

PMID- 16576785
TI  - Sets of Completely Independent Postulates for Cyclic Order.

PMID- 16576786
TI  - The Development of a Frequency Function and Some Comments of Curve Fitting.

PMID- 16576788
TI  - Condition that an Electron Describe a Geodesic.

PMID- 16576787
TI  - On Certain New Topological Invariants of a Manifold.

PMID- 16576789
TI  - Linkage of Dutch, English, and Angora in Rabbits.

PMID- 16576790
TI  - Distinction between Primary and Secondary Chromosomal Mutants in Datura.

PMID- 16576791
TI  - The Configurations and Sizes of the Chromosomes in the Trivalents of 25
      Chromosome Daturas.

PMID- 16576793
TI  - On Thermal Emission and Evaporation from Water.

PMID- 16576792
TI  - Duration of Molecules in Upper Quantum States.

PMID- 16576794
TI  - On Secondary and Tertiary X-Rays from Germanium, Etc.

PMID- 16576795
TI  - Exhibit of Telephonic Excitation of Acoustic Pressure.

PMID- 16576796
TI  - New Topological Invariants Expressible as Tensors.

PMID- 16576798
TI  - Electrodynamics in the General Relativity Theory.

PMID- 16576797
TI  - Inheritance in Nicotiana Tabacum: V. The Occurrence of Haploid Plants in
      Interspecific Progenies.

PMID- 16576799
TI  - Principal Directions in an Affine-Connected Manifold of Two Dimensions.

PMID- 16576800
TI  - A Statistical Discussion of Sets of Precise Astronomical Measurements:
      Parallaxes.

PMID- 16576802
TI  - Effective Radii of Gas Molecules.

PMID- 16576803
TI  - Note on Absorption Measurements of the X-Rays Reflected from a Calcite Crystal.

PMID- 16576801
TI  - The Quantum Theory of the Fraunhofer Diffraction.

PMID- 16576804
TI  - The Secondary and Tertiary Rays from Chemical Elements of Small Atomic Number Due
      to Primary X-Rays from a Molybdenum Target.

PMID- 16576806
TI  - The Behavior of Low Velocity Electrons in Methane Gas.

PMID- 16576805
TI  - Density and Diffusion of Gases Measured by Displacement Interferometry.

PMID- 16576807
TI  - Is Pneumonia Increasing?

PMID- 16576808
TI  - Prime Power Substitution Groups Whose Conjugate Cycles Are Commutative.

PMID- 16576809
TI  - An Extension of the Theorem That No Countable Point Set Is Perfect.

PMID- 16576811
TI  - Concerning the Division of the Plane by Continua.

PMID- 16576810
TI  - Concerning the Prime Parts of Certain Continua Which Separate the Plane.

PMID- 16576812
TI  - The Partial Genetic Independence in Size of the Various Parts of the Body.

PMID- 16576813
TI  - Are the Various Parts of the Body Genetically Independent in Size?

PMID- 16576814
TI  - On the Longevity of Spathidium Spathula without Endomixis or Conjugation.

PMID- 16576815
TI  - A Possible Explanation of Tertiary Line Spectra in X-Rays.

PMID- 16576816
TI  - On the Theory of the Tertiary Radiation Produced by Impacts of Photo-Electrons.

PMID- 16576817
TI  - Absorption Measurements of Certain Changes in the Average Wave-Length of Tertiary
      X-Rays.

PMID- 16576819
TI  - Historical Tradition and Oriental Research.

PMID- 16576818
TI  - The Series Spectra of the Stripped Boron Atom (BIII).

PMID- 16576820
TI  - Second Note: Electrodynamics in the General Relativity Theory.

PMID- 16576821
TI  - The Reflection of Characteristic Bromine X-Radiation by a Crystal of Potassium
      Bromide.

PMID- 16576822
TI  - Quantitative Theory of the Influence Electrostatic Generator.

PMID- 16576823
TI  - Scattered X-Rays.

PMID- 16576824
TI  - On a Stony Meteorite from Anthony, Harper County, Kansas, and a Recently Found
      Meteoric Iron from Mejillones, Chile.

PMID- 16576826
TI  - The Constitution of Columbia Yellow (Chloramine Yellow).

PMID- 16576825
TI  - On a Meteoric Iron from Four Corners, San Juan County, New Mexico.

PMID- 16576827
TI  - A Synopsis of the Ionization Potentials of the Elements.

PMID- 16576828
TI  - The Inheritance of a Retinal Abnormality in White Mice.

PMID- 16576829
TI  - Action of Dilute Alcohol on Human Subjects.

PMID- 16576830
TI  - On the Simultaneous Jumping of Two Electrons in Bohr's Model.

PMID- 16576831
TI  - The Compton and Duane Effects.

PMID- 16576832
TI  - Coulomb's Law and the Hydrogen Spectrum.

PMID- 16576834
TI  - Ionic Mobilities in Gaseous Mixtures.

PMID- 16576833
TI  - Density and Diffusion Measurement by Displacement Interferometry in Extreme
      Cases.

PMID- 16576835
TI  - Concerning Upper Semi-Continuous Collections of Continua which do not Separate a
      Given Continuum.

PMID- 16576836
TI  - The Spectrohelioscope.

PMID- 16576837
TI  - The Constitution of the So-Called "Pechmann Dyes" and the Mechanism of Their
      Formation from Beta-Benzoylacrylic Acid.

PMID- 16576838
TI  - The Derivation of Electromagnetic Fields from a Basic Wave-Function.

PMID- 16576839
TI  - The Influence on Secondary X-Ray Spectra of Placing the Tube and Radiator in a
      Box.

PMID- 16576840
TI  - The Influence on Secondary X-Ray Spectra of Placing the Tube and Radiator in a
      Box.

PMID- 16576841
TI  - Further Experiments on the Refraction of X-Rays in Pyrites.

PMID- 16576842
TI  - An Improved Method of Measuring the Specific Heats of Metals at High
      Temperatures.

PMID- 16576843
TI  - Note on the Pressure and Currents in the Sun's Atmosphere.

PMID- 16576844
TI  - Convection Currents in Stellar Atmospheres.

PMID- 16576845
TI  - A Statistical Discussion of Sets of Precise Astronomical Measurements: III;
      Masses of the Stars.

PMID- 16576846
TI  - The Ionization Potentials of Hydrogen as Interpreted by Positive Ray Analysis.

PMID- 16576847
TI  - The Polarization Angle X-Rays Scattered by Paraffin.

PMID- 16576848
TI  - The Combination of Hydrogen and Oxygen in the Presence of Activated Mercury.

PMID- 16576849
TI  - Some Properties of Single Metal Crystals.

PMID- 16576850
TI  - Effect of Insulin on the Lactic Fermentation.

PMID- 16576851
TI  - A New Group of Dyes from Poison Gases through the 2-Aminothiazoles as
      Intermediates: The Preparation of Thiazole Dyes of Doebner Violet Type.

PMID- 16576852
TI  - The Synthesis of Terephthal Green and Terephthal Brilliant Green from Cymene.

PMID- 16576854
TI  - A Statistical Discussion of Sets of Precise Astronomical Measurements.

PMID- 16576853
TI  - Further Experiments in the Field of the Terephthalic Acid Derivatives.

PMID- 16576855
TI  - Note on the Thermokinetics of Dolichoderine Ants.

PMID- 16576856
TI  - The Mobilities of the Positive Ions in Helium.

PMID- 16576857
TI  - The Density of Oxygen.

PMID- 16576858
TI  - Observations on the Fauna of Thermal Waters.

PMID- 16576859
TI  - On the Occurrence in Rabbits of Linkage in Inheritance between Albinism and Brown
      Pigmentation.

PMID- 16576860
TI  - A General Type of Singular Point.

PMID- 16576861
TI  - Topological Invariants of Manifolds.

PMID- 16576862
TI  - The Neutral Bath and Its Relation to Body Heat.

PMID- 16576863
TI  - Body Posture and Minor Muscular Movements as Affecting Heat Production.

PMID- 16576864
TI  - The Relative Intensities of Fluorescent and Scattered X-Rays.

PMID- 16576865
TI  - Note on the Quantum Theory of the Reflection of X-Rays.

PMID- 16576866
TI  - A New Principle of Equilibrium.

PMID- 16576867
TI  - Studies on Disease Resistance in the Onion.

PMID- 16576868
TI  - Notes on Stellar Statistics: IV. On The Relation between the Mean Values of the
      nu and tau Components of Proper Motion.

PMID- 16576869
TI  - Astrophysical Data Bearing on the Relative Abundance of the Elements.

PMID- 16576870
TI  - On the Projective and Equi-Projective Geometries of Paths.

PMID- 16576871
TI  - Projective Normal Coordinates for the Geometry of Paths.

PMID- 16576872
TI  - Note on the Projective Geometry of Paths.

PMID- 16576873
TI  - Determination of the Stresses in a Beam by Means of the Principle of Least Work.

PMID- 16576874
TI  - Researches on Selenium Organic Compounds: V. A Simple Method for the Synthesis of
      2-Substituted Benzoselenazoles.

PMID- 16576875
TI  - The Reflection of X-Rays by Alkali Halide Crystals.

PMID- 16576876
TI  - Note on the Diffraction of X-Rays by a Wedge-Shaped Slit.

PMID- 16576877
TI  - The Compton Effect with Hard X-Rays.

PMID- 16576878
TI  - The Heat Capacity of Solid Aliphatic Crystals.

PMID- 16576880
TI  - The Cultivation of Endamoeba Histolytica.

PMID- 16576879
TI  - The Density and Atomic Weight of Helium.

PMID- 16576881
TI  - The Rat as a Possible Carrier of the Dysentery Amoeba.

PMID- 16576882
TI  - Linear Connections of a Space Which Are Determined by Simply Transitive
      Continuous Groups.

PMID- 16576883
TI  - Note on a Theorem by H. Kneser.

PMID- 16576884
TI  - Associated Types of Linear Connection.

PMID- 16576885
TI  - Conformal Correspondence of Riemann Spaces.

PMID- 16576886
TI  - Pinhole Probe Measurements of the Phase Change of the Telephonic End Plates,
      Acting on a Closed Cylindrical Air Column in Longitudinal Acoustic Vibration.

PMID- 16576887
TI  - On the Boltzmann Equation rho = rho(0) exp (-w/kt).

PMID- 16576888
TI  - The Band Spectra of Crystals and Complex Gases.

PMID- 16576889
TI  - The Frequency Distribution of Some Measured Parallaxes and of the Parallaxes
      Themselves.

PMID- 16576890
TI  - The Effect of Varying Mass on a Binary System.

PMID- 16576891
TI  - The Logistic or Autocatalytic Grid.

PMID- 16576892
TI  - The Paramagnetism of "Odd Molecules".

PMID- 16576893
TI  - The Activation of Hydrogen by Excited Mercury Atoms.

PMID- 16576894
TI  - What Is Humus?

PMID- 16576895
TI  - Concerning the Separation of Point Sets by Curves.

PMID- 16576896
TI  - The Soil Population.

PMID- 16576897
TI  - The Precipitin Reaction of Thyroglobulin: Specificness; Presence of Thyroglobulin
      in Human Thyroid Veins; Production by Rabbit of Precipitin for Rabbit
      Thyroglobulin; Thyroglobulin in the Foetal Thyroid and in Exophthalmic Goiter.

PMID- 16576898
TI  - The Internal Secretion of the Parathyroid Glands.

PMID- 16576899
TI  - An Experimental Determination of the Critical Excitation Frequency for the
      Production of Fluorescent X-Radiation.

PMID- 16576900
TI  - The Calculation of the X-Ray Diffracting Power at Points in a Crystal.

PMID- 16576901
TI  - The Effect of Commutation of Impedances on the Acoustic Pressure Produced by
      Paired Telephonic Systems.

PMID- 16576902
TI  - A Statistical Quantum Theory of Regular Reflection and Refraction.

PMID- 16576903
TI  - The Distribution of Diffracting Power in Sodium Chloride.

PMID- 16576904
TI  - The Distribution of Diffracting Power in Certain Crystals.

PMID- 16576905
TI  - Ionization Produced in Gaseous Reactions.

PMID- 16576906
TI  - Ionization of Mercury Vapor by Ultra-Violet Light.

PMID- 16576907
TI  - Modified and Unmodified Scattering Coefficients of X-Rays in Matter.

PMID- 16576908
TI  - The Energy Reappearing as Characteristic X-Rays when X-Rays Are Absorbed in
      Copper.

PMID- 16576909
TI  - Encystment and the Life Cycle in the Ciliate Didinium Nasutum.

PMID- 16576910
TI  - Studies on Biochemical Differences between (+) and (-) Sexes in Mucors: 1.
      Tellurium Salts as Indicators of the Reduction Reaction.

PMID- 16576911
TI  - Tetraploidy in Citrus.

PMID- 16576912
TI  - Deviation from the Regular as an Art Principle.

PMID- 16576913
TI  - The Role of Mental Measurement in the Discovery and Motivation of the Gifted
      Student.

PMID- 16576914
TI  - Arithmetization in the History of Mathematics.

PMID- 16576915
TI  - Skin Temperature and Heat Loss.

PMID- 16576917
TI  - Energy Transformations in an Unobstructed Air Current, in an Air Current
      Containing a Dry Obstacle, and in an Air Current Containing an Evaporating
      Surface; with Application to an Aerodynamic Psychrometer and to the Measurement
      of Atmospheric Humidity.

PMID- 16576916
TI  - The Passage of Slow Canal Rays through Hydrogen.

PMID- 16576918
TI  - Note on the Experimental Determination of the Relative Intensities of Some of the
      Molybdenum and Copper K Series Lines and the Tungsten L Series Lines.

PMID- 16576919
TI  - X-Rays Scattered by Molybdenum.

PMID- 16576920
TI  - Ratio of Intensities of Unmodified and Modified Lines in Scattered X-Rays.

PMID- 16576921
TI  - The Effect of Light on the Behavior of Selenium Contact Rectifiers.

PMID- 16576922
TI  - The Acoustic Pressure in Tubes Capped by High Resistance Telephones, Vibrating in
      Different Phases.

PMID- 16576923
TI  - The Age and Affinities of the Tertiary Flora of Western Canada.

PMID- 16576924
TI  - The Metastable 2p(3)-State of Mercury Atoms.

PMID- 16576925
TI  - Some Experiments on Collisions of the Second Kind.

PMID- 16576926
TI  - General Criterion for the Circular Locus of the Current Vector in A. C. Circuits
      and Machinery.

PMID- 16576927
TI  - Postulates for Reversible Order on a Closed Line (Separation of Point-Pairs).

PMID- 16576928
TI  - The Hypothesis of Inhibition by Drainage.

PMID- 16576929
TI  - A Test of Electromagnetic Theory of the Hydrogen Vortices Surrounding Sun-Spots.

PMID- 16576930
TI  - Recent Evolution in Milk Secretion of Guernsey Cattle.

PMID- 16576931
TI  - Elimination of Chromosomes Due to a Mutant (Minute-N) in Drosophila Melanogaster.

PMID- 16576932
TI  - Haploidy in Drosophila Melanogaster.

PMID- 16576933
TI  - Plant Growth.

PMID- 16576935
TI  - Fertility of the Rat, Mus Norvegicus.

PMID- 16576934
TI  - The Third Linkage Group in Oenothera.

PMID- 16576936
TI  - Invariants of Relative Quadratic Differential Forms.

PMID- 16576937
TI  - A Property Which Characterizes Continuous Curves.

PMID- 16576938
TI  - Telephonic Coupling of Acoustic and Electrical Osciliations Evidenced by the
      Pinhole Probe.

PMID- 16576939
TI  - Interpretation of the Hydrogen and Helium Spectra.

PMID- 16576940
TI  - Radiation Emitted by Optically Excited Zinc Vapor.

PMID- 16576941
TI  - On Contact Rectification by Metallic Germanium.

PMID- 16576942
TI  - The Origin of Species: II. Distinctions between Rectigradations and Allometrons.

PMID- 16576943
TI  - Vital Statistics of the National Academy of Sciences: I. Age at Election.

PMID- 16576944
TI  - Vital Statistics of the National Academy of Sciences: II. Elections of Young Men.

PMID- 16576946
TI  - Vital Statistics of the National Academy of Sciences: IV. The Present Limitation
      to Total Membership and Other Matters.

PMID- 16576945
TI  - Vital Statistics of the National Academy of Sciences: III. Mortality.

PMID- 16576947
TI  - Researches on Thiazoles: X. The Synthesis of Some 2-Phenyl-benzothiazole Arsonic
      Acids.

PMID- 16576948
TI  - The Origin of Terrestrial Helium and Its Association with Other Gases.

PMID- 16576949
TI  - Reddish-A Frequently "Mutating" Character in Drosophila Virilis.

PMID- 16576950
TI  - The Explanation of Hybrid Vigor.

PMID- 16576951
TI  - The Direct Results of Mendelian Segregation.

PMID- 16576952
TI  - The Density and Atomic Weight of Helium: II.

PMID- 16576953
TI  - The Nature of Light.

PMID- 16576954
TI  - The Role of the Faraday Cylinder in the Measurement of Electron Currents.

PMID- 16576955
TI  - The Quantum Theory of the Dielectric Constant of Hydrogen Chloride and Similar
      Gases.

PMID- 16576956
TI  - The Mobility of Gaseous Ions in HCl Gas and HCl Air Mixtures.

PMID- 16576958
TI  - High Frequency Rays of Cosmic Origin.

PMID- 16576957
TI  - The Mobility of Gas Ions in HCl Mixtures and the Nature of the Ion.

PMID- 16576959
TI  - The Joule-Thomson Effect in Air.

PMID- 16576960
TI  - On Normal Coordinates in the Geometry of Paths.

PMID- 16576961
TI  - A Simple Derivation of Kronecker's Relation among the Minors of a Symmetric
      Determinant.

PMID- 16576963
TI  - Resonant Acoustic and Electric Oscillations Released by the Relatively Slow
      Spring Break.

PMID- 16576962
TI  - On the Attachment of Non-Homologous Chromosomes at the Reduction Division in
      Certain 25-Chromosome Daturas.

PMID- 16576964
TI  - On the Reflection by a Crystal of Its Own Characteristic Radiation.

PMID- 16576965
TI  - Note on the "Selective Reflection" of X-Rays by Crystals of Potassium Bromide.

PMID- 16576966
TI  - Systematic Relations between Electronic Structure and Band-Spectrum Structure in
      Diatomic Molecules: I.

PMID- 16576968
TI  - The Electronic States of the Helium Molecule.

PMID- 16576967
TI  - Systematic Relations between Electronic Structure and Band-Spectrum Structure in
      Diatomic Molecules: II. The ZnH, CdH and HgH Molecules and Their Spectra.

PMID- 16576969
TI  - Variations in the Photo-Electric Sensitivity of Platinum.

PMID- 16576970
TI  - Radiation and the Disintegration and Aggregation of Atoms.

PMID- 16576972
TI  - Formation of Ozone by Optically Excited Mercury Vapor.

PMID- 16576973
TI  - Diffusion of Electrons.

PMID- 16576971
TI  - A New Kind of Test of the Correspondence Principle Based on the Prediction of the
      Absolute Intensities of Spectral Lines.

PMID- 16576974
TI  - Correlation between Shape and Behavior of a Chromosome.

PMID- 16576976
TI  - On Various Geometries Giving a Unified Electric and Gravitational Theory.

PMID- 16576975
TI  - The Genetic Basis of Susceptibility to Tissue Transplants.

PMID- 16576977
TI  - Studies on Biochemical Differences between (+) and (-) Sexes in Mucors: 2. A
      Preliminary Report on the Manoilov Reaction and Other Tests.

PMID- 16576978
TI  - Biochemical Differences between Sexes in Green Plants.

PMID- 16576979
TI  - The Mucor Parasite Parasitella in Relation to Sex.

PMID- 16576980
TI  - The Physiological Principle of Minimum Work: I. The Vascular System and the Cost
      of Blood Volume.

PMID- 16576981
TI  - The Significance of Changes in the Electrical Resistance of the Body during
      Sleep.

PMID- 16576982
TI  - Mutually Counteracting Pinhole Probes.

PMID- 16576983
TI  - Transition Probabilities and Principal Quantum Numbers.

PMID- 16576985
TI  - Thermodynamic Derivation of a Black Body Radiation Isotherm.

PMID- 16576984
TI  - Absorption and Resonance Radiation in Excited Helium and the Structure of the
      3889 Line.

PMID- 16576986
TI  - Critical Potentials and the Heat of Dissociation of Hydrogen as Determined from
      Its Ultra-Violet Band Spectrum.

PMID- 16576987
TI  - Curved Space-Time and Radiation.

PMID- 16576989
TI  - On the Occurrence in the House Mouse of Mendelizing Structural Defect of the
      Retina Producing Blindness.

PMID- 16576988
TI  - Linkage between a Flower Color Factor and Self-Sterility Factors.

PMID- 16576991
TI  - On Laguerre's Series: First Note.

PMID- 16576990
TI  - Vital Statistics of the National Academy of Sciences: V. The Growth of the
      Academy.

PMID- 16576992
TI  - On Laguerre's Series: Second Note.

PMID- 16576993
TI  - Groups Containing a Relatively Small Number of Sylow Subgroups.

PMID- 16576994
TI  - Bending of a Curved Tube of Circular Cross Section.

PMID- 16576995
TI  - The Heat Capacity of Solid Aliphatic Crystals: II.

PMID- 16576997
TI  - The Intensity of Reflection of X-Rays by Lithium, Sodium and Calcium Fluorides.

PMID- 16576996
TI  - The Effect of Crystal Size upon the Intensity of X-Ray Reflection.

PMID- 16576998
TI  - Note on the Postulates of the Matrix Quantum Dynamics.

PMID- 16576999
TI  - Conformal Invariants.

PMID- 16577000
TI  - Generalization of Kronecker's Relation among the Minors of a Symmetric
      Determinant.

PMID- 16577001
TI  - On the Classical Dirichlet Problem for General Domains.

PMID- 16577002
TI  - The Evidence for Changes in the Rate of Rotation of the Earth and Their
      Geophysical Consequences.

PMID- 16577003
TI  - The Reddish Blue Arcs and the Reddish Blue Glow of the Retina: Seeing Your Own
      Nerve Currents through Bioluminescence.

PMID- 16577004
TI  - The Metabolic Effect of Enemata of Alcohol, Dextrose and Levulose in Humans.

PMID- 16577006
TI  - On the Zeros of Functions Associated with a Linear System of the Second Order.

PMID- 16577005
TI  - Postulates in the History of Scienec.

PMID- 16577007
TI  - Concerning Irreducibly Connected Sets and Irreducible Continua.

PMID- 16577008
TI  - Interpretation of Deviations from Ohm's Law.

PMID- 16577009
TI  - Rubidium and Caesium-Like Doublets of Stripped Atoms.

PMID- 16577010
TI  - The Fine Structure of Certain Lines and Energy Levels of Cadmium.

PMID- 16577012
TI  - Ionization in Reacting Gases.

PMID- 16577011
TI  - On the Spectrum of Argon.

PMID- 16577013
TI  - Localization of Formative Agencies in Hydra.

PMID- 16577014
TI  - Inhibition of Regeneration in Two-Headed or Two-Tailed Planarians.

PMID- 16577016
TI  - Relations between Stature and Chest-Girth Formula of Normality and Normal Values.

PMID- 16577015
TI  - Inhibition of Regeneration in Planarians by Grafting: Technique of Grafting.

PMID- 16577017
TI  - Social Selection in a Mixed Population.

PMID- 16577018
TI  - A Preliminary Report on the Magnetic Susceptibilities of Some Cases.

PMID- 16577019
TI  - A Possible Explanation on the "Glaser Effect.".

PMID- 16577021
TI  - The Rotational Energy of the Polyatomic Molecule as an Explicit Function of the
      Quantum Numbers.

PMID- 16577022
TI  - The Dielectric Constant of Symmetrical Polyatomic Dipole-Gases on the New Quantum
      Mechanics.

PMID- 16577020
TI  - Stripped Atoms of the First Long Period.

PMID- 16577023
TI  - Tropisms of Mammals.

PMID- 16577024
TI  - Gas Ion Mobilities in Ether-Hydrogen Mixtures.

PMID- 16577025
TI  - A Refinement of the Michelson-Morley Experiment.

PMID- 16577026
TI  - On the Evaluation of Certain Integrals Important in the Theory of Quanta.

PMID- 16577027
TI  - The New Quantum Theory and the Zeeman Effect.

PMID- 16577029
TI  - The Dispersion of Atomic Hydrogen: II-A Calculation.

PMID- 16577028
TI  - The Dispersion of Atomic Hydrogen: I-A Measure.

PMID- 16577030
TI  - The Development of Mendelian Characters in Aplocheilus Latipes.

PMID- 16577031
TI  - On the Closure of Certain Assemblages of Trigonometrical Functions.

PMID- 16577032
TI  - On a Type of Lorentz Transformations.

PMID- 16577034
TI  - Displacements in a Geometry of Paths Which Carry Paths into Paths.

PMID- 16577033
TI  - Cyclicly Connected Continuous Curves.

PMID- 16577035
TI  - Photo-Electric Emission, Thermionic Emission and Peltier Effect: (From the Point
      of View of Dual Electric Conduction).

PMID- 16577036
TI  - The Transverse Thermo-Electric Effect in Metal Crystals.

PMID- 16577037
TI  - The Effect of Velocity Distribution on the Deflection of Atoms in an Inhomogenous
      Magnetic Field.

PMID- 16577038
TI  - Pinhole Probe Record of the Closed Organ Pipe.

PMID- 16577039
TI  - A Comparison of the Thermionic and Photoelectric Work Functions for Clean
      Tungsten.

PMID- 16577040
TI  - The Quantization of the Rotational Motion of the Polyatomic Molecule by the New
      Wave Mechanics.

PMID- 16577041
TI  - A Note on the Spectrum of Doubly Ionized Scandium.

PMID- 16577042
TI  - The Thermal Decomposition of Ammonia upon the Surface of a Molybdenum Wire.

PMID- 16577043
TI  - Eskimos and Plants.

PMID- 16577044
TI  - Chromosome and Gene Mutations in Datura Following Exposure to Radium Rays.

PMID- 16577045
TI  - The Chromosomal Constitution of Nubbin, a Compound (2n + 1) Type in Datura.

PMID- 16577046
TI  - On the Expansion of Harmonic Functions in Terms of Harmonic Polynomials.

PMID- 16577047
TI  - On the Correction to Saha's Formula for Small Deviations from Thermodynamic
      Equilibrium.

PMID- 16577048
TI  - Chemical Constants and Absolute Entropy.

PMID- 16577049
TI  - On Chemical Activation by Collisions.

PMID- 16577051
TI  - On the Determination of the Apparent Diameters of the Ions in the Debye-Huckel
      Theory of Strong Electrolytes.

PMID- 16577050
TI  - A Case of Negative Catalysis in a Homogeneous System.

PMID- 16577052
TI  - New Infra-Red Absorption Bands of Methane.

PMID- 16577053
TI  - On the Nature of Light.

PMID- 16577054
TI  - Bands in the Extreme Ultra-Violet Spectrum of a Helium Discharge.

PMID- 16577055
TI  - White-Light Interference Fringes with a Thick Glass Plate in One Path: Part II.

PMID- 16577056
TI  - Molecular Space Array in Liquid Primary Normal Alcohols: The Cybotactic State.

PMID- 16577057
TI  - Pinhole Probe Measurements with Massive Cylindrical Air Columns.

PMID- 16577058
TI  - Atomic Lattices and Atomic Dimensions.

PMID- 16577060
TI  - Nucleus and Cytoplasm in Relation to Differential Pollen-Tube Growth.

PMID- 16577059
TI  - The Magnetic Dipole in Undulatory Mechanics.

PMID- 16577061
TI  - Abnormalities in Pollen-Tube Growth in Datura Due to the Gene "Tricarpel".

PMID- 16577062
TI  - Magenta-Alpha-A Third Frequently Mutating Character in Drosophila Virilis.

PMID- 16577063
TI  - Pollen-Tube Growth in Lythrum Salicaria.

PMID- 16577064
TI  - Bending of a Quasi-Ellipsoidal Shell with Special Reference to Rigid Airships.

PMID- 16577065
TI  - Influence of Iron Content on Mortar Strength.

PMID- 16577066
TI  - A Quantitative Treatment of Deviations from Raoult's Law.

PMID- 16577067
TI  - The Thermal Decomposition of Ozone.

PMID- 16577068
TI  - Concerning Points of a Continuous Curve That Are Not Accessible from Each Other.

PMID- 16577069
TI  - Recent Progress of Investigations by Symbolical Methods of the Invariants of Bi
      Ternary Quantics.

PMID- 16577070
TI  - A Dynamical Theory of Economic Equilibrium.

PMID- 16577071
TI  - On the Foundations of the Theory of Discontinuous Groups of Linear
      Transformations.

PMID- 16577073
TI  - A Stratigraphic Study in the Gila-Salt Region, Arizona.

PMID- 16577074
TI  - The Infra-Red Absorption Spectra of Acetylene (C(2)H(4)), Ethylene (C(2)H(4)) and
      Ethane (C(2)H(6)).

PMID- 16577072
TI  - On the Formation of Groups of Linear Transformations by Combination.

PMID- 16577075
TI  - The Spectrum of CO(2).

PMID- 16577076
TI  - The Entropy of Radiation.

PMID- 16577078
TI  - Thermionic Emission and the "Universal Constant" A.

PMID- 16577079
TI  - Lagrangian Functions and Schrodinger's Rule.

PMID- 16577080
TI  - Two Remarks on the Wave-Theory of Mechanics.

PMID- 16577077
TI  - Linear Elements of the Electromagnetic Pinhole Graphs.

PMID- 16577081
TI  - Heats of Condensation of Positive Ions and the Mechanism of the Mercury Arc.

PMID- 16577082
TI  - Series Spectra of Silver-Lake Atoms.

PMID- 16577083
TI  - Term-Structure and Zeeman Effect of the Arc Spectrum of Tin: (Preliminary
      Report).

PMID- 16577084
TI  - The Activation of Gases by Adsorption.

PMID- 16577085
TI  - The Death Rate from Diphtheria in Massachusetts for 51 Years, 1875-1925.

PMID- 16577087
TI  - A Summary of Some of the Results from an Experimental Study of the East Kentucky
      Mountaineers.

PMID- 16577086
TI  - A Fundamental Theorem in Modifiability.

PMID- 16577088
TI  - Crossing Over in the Third Linkage Group in Oenothera.

PMID- 16577090
TI  - Editorial Note.

PMID- 16577089
TI  - Groups Generated by Two Operators of Order Three Whose Product Is of Order Three.

PMID- 16577091
TI  - Luminescence Due to Radioactivity.

PMID- 16577092
TI  - Radiation and Absorption on Schrodinger's Theory.

PMID- 16577093
TI  - The Quantum Theory of Quasi-Unimolecular Gas Reactions.

PMID- 16577094
TI  - The Theory of the Decomposition of Azomethane.

PMID- 16577095
TI  - Fundamental Frequencies, Interatomic Forces and Molecular Properties.

PMID- 16577096
TI  - The Effect of Intensive Drying on the Vapor Pressure and Vapor Density of
      Ammonium Chloride.

PMID- 16577097
TI  - Some Effects of Dietary Insufficiency in the Ciliate Didinium Nasutum.

PMID- 16577098
TI  - Mendelian Inheritance with Assortive Mating.

PMID- 16577099
TI  - Genetic Evidence of a Selective Segregation of Chromosomes in a Second Species of
      Sciara (Diptera).

PMID- 16577100
TI  - The "Outside-In" Oenothera Flower, a New Morphological Type Produced by the
      Interaction of Two Recessive Mendelian Factors.

PMID- 16577101
TI  - Linkage with Crossing-Over between Rubricalyx Buds and Old-Gold Flower Color in
      Oenothera.

PMID- 16577102
TI  - A New Proof of the Lefschetz Formula on Invariant Points.

PMID- 16577104
TI  - Projective Tensors and Connections.

PMID- 16577103
TI  - Note on Projective Coordinates.

PMID- 16577105
TI  - The Molecular Structures of Methane.

PMID- 16577106
TI  - Additional Lines in the K Series of Molybdenum and the Natural Breadth of
      Spectral Lines.

PMID- 16577108
TI  - Experiments with Modified Mucronate Electrodes.

PMID- 16577109
TI  - The Mobilities of Gaseous Ions in H(2)S-H(2) Mixtures.

PMID- 16577107
TI  - The Correspondence Principle in the Statistical Interpretation of Quantum
      Mechanics.

PMID- 16577111
TI  - The Fermi Statistical Postulate; Examination of the Evidence in Its Favor.

PMID- 16577110
TI  - On the Quantum Theory of the Autoelectric Field Currents.

PMID- 16577112
TI  - Sommerfeld's Electron-Theory of Metals.

PMID- 16577113
TI  - Electron "Free Path" and Supra-Conductivity in Metals.

PMID- 16577114
TI  - Dispersion of Long Wave-Length X-Rays in Platinum and Calcite.

PMID- 16577116
TI  - Is Pituitary Secretion Concerned in the Inheritance of Body-Size?

PMID- 16577117
TI  - On the Contours of Stellar Absorption Lines, and the Composition of Stellar
      Atmospheres.

PMID- 16577115
TI  - Mobilities of Gaseous Ions in SO(2) and SO(2)-H(2) Mixtures.

PMID- 16577118
TI  - Regional Isostatic Reduction of Gravity Determinations.

PMID- 16577119
TI  - Proof of Isostasy by a Simple Gravity Reduction Method.

PMID- 16577120
TI  - Singular Points of Vector Fields under General Boundary Conditions.

PMID- 16577121
TI  - Remark on the Number of Classes of Binary Quadratic Forms of a Given Negative
      Determinant.

PMID- 16577122
TI  - Concerning Certain Types of Non-Cut Points, with an Application to Continuous
      Curves.

PMID- 16577124
TI  - Criteria for the Simplification of Algebraic Plane Curves.

PMID- 16577123
TI  - Concerning Irreducible Continua.

PMID- 16577125
TI  - The Photo-Electric and Thermionic Properties of Iron.

PMID- 16577126
TI  - Evidence for the Continuous Creation of the Common Elements Out of Positive and
      Negative Electrons.

PMID- 16577127
TI  - The General X-Radiation from Mercury Vapor.

PMID- 16577128
TI  - On the Quantity of Electricity Discharged in a Lightning Stroke.

PMID- 16577129
TI  - Secondary Electrons from Cobalt.

PMID- 16577130
TI  - Sparks of the Induction Coil between Mucronate Electrodes.

PMID- 16577131
TI  - The Adsorption Kinetics for Molecules Attached at More than One Point.

PMID- 16577132
TI  - Characteristic of Homogeneous, Exothermic Gas Reactions.

PMID- 16577133
TI  - On the Mechanism of Chromosome Behavior in Male and Female Drosophila.

PMID- 16577134
TI  - Normal and "Rodless" Retinae of the House Mouse with Respect to the Electromotive
      Force Generated through Stimulation by Light.

PMID- 16577135
TI  - Radiation and Relativity: I.

PMID- 16577136
TI  - On the Absolute Magnitudes of the Class M Stars.

PMID- 16577137
TI  - On the Constancy of the Light of Red Stars, with Forty New Variables of This
      Class.

PMID- 16577138
TI  - Family Traits as Determined by Heredity and Environment.

PMID- 16577140
TI  - Studies of the Galactic Center: II. Preliminary Indication of a Massive Galactic
      Nucleus.

PMID- 16577139
TI  - Studies of the Galactic Center: I. The Program for Milky Way Variable Stars.

PMID- 16577141
TI  - The Determination of Absolute-Magnitude Dispersion with Application to Giant M
      Stars.

PMID- 16577142
TI  - Gudermannian Complex Angles.

PMID- 16577144
TI  - The Quenching of Cadmium Resonance Radiation.

PMID- 16577143
TI  - New Studies in Polymerization: I. Polymerization of Styrene.

PMID- 16577145
TI  - The Influence of Food upon Longevity.

PMID- 16577146
TI  - The Interferometer U-Gauge with Closed Auxiliary Reservoirs.

PMID- 16577147
TI  - Characteristic Differentiation in the Spectra of Saturated Hydrocarbons.

PMID- 16577148
TI  - Are Characteristic X-Rays Polarized?

PMID- 16577149
TI  - The Origin of the Continuous Spectrum of the Hydrogen Molecule.

PMID- 16577150
TI  - The Critical Potentials of Molecular Hydrogen.

PMID- 16577151
TI  - The Structure of the Compton Shifted Line.

PMID- 16577152
TI  - Some Multiplets of Doubly Ionized Lead.

PMID- 16577153
TI  - Spectral Intensities of Radiation from Non-Harmonic and Aperiodic Systems.

PMID- 16577154
TI  - The Aurora Red Line.

PMID- 16577155
TI  - A Visual Method of Observing the Influence of Atmospheric Conditions on Radio
      Reception.

PMID- 16577156
TI  - On the Energy of Deformation of an Elastic Solid.

PMID- 16577157
TI  - The Survival of Intelligence.

PMID- 16577158
TI  - THE LONGITUDE OF THE GALACTIC CENTER AS DERIVED FROM THE INTENSITIES OF DETACHED
      CALCIUM LINES.

PMID- 16577159
TI  - THE LARGE RADIAL VELOCITY OF N. G. C. 7619.

PMID- 16577161
TI  - STUDIES OF THE GALACTIC CENTER. IV. ON THE TRANSPARENCY OF THE GALACTIC STAR
      CLOUDS.

PMID- 16577160
TI  - A RELATION BETWEEN DISTANCE AND RADIAL VELOCITY AMONG EXTRA-GALACTIC NEBULAE.

PMID- 16577162
TI  - THE VISUAL ACUITY OF THE BEE AND ITS RELATION TO ILLUMINATION.

PMID- 16577163
TI  - SOME PROBLEMS OF BUSINESS FORECASTING.

PMID- 16577164
TI  - THE AUTOXIDATION OF HYDROQUINONES CATALYZED BY MANGANOUS SALTS IN ACID SOLUTIONS.
      A REACTION WHOSE VELOCITY IS PROPORTIONAL TO THE DRIVING FORCE.

PMID- 16577165
TI  - THE TEMPERATURE COEFFICIENTS OF SOME PHOTOCHEMICAL REACTIONS.

PMID- 16577166
TI  - LINEAR TRANSFORMATIONS IN HILBERT SPACE. I. GEOMETRICAL ASPECTS.

PMID- 16577167
TI  - ON COMMUTATION RULES IN THE ALGEBRA OF QUANTUM MECHANICS.

PMID- 16577168
TI  - SOME THEOREMS CONCERNING PROPERLY IRREGULAR CYCLOTOMIC FIELDS.

PMID- 16577170
TI  - CONTROL OF AN ARC DISCHARGE BY MEANS OF A GRID.

PMID- 16577169
TI  - THE THERMODYNAMICS OF GASES WHICH SHOW DEGENERACY (ENTARTUNG).

PMID- 16577171
TI  - THE HEAT OF DISSOCIATION OF NITROGEN.

PMID- 16577172
TI  - EXPONENTIAL YIELD OF POSITIVE IONS IN ARGON.

PMID- 16577174
TI  - ADIABATIC EXPANSION IN CASE OF VANISHING INCREMENTS. II.

PMID- 16577173
TI  - ON THE RAMAN EFFECT IN DIATOMIC GASES.

PMID- 16577175
TI  - ON ELECTRONS THAT ARE "PULLED OUT" FROM METALS.

PMID- 16577176
TI  - A PRELIMINARY REPORT ON THE MEASUREMENT OF THE Kalpha LINE OF CARBON.

PMID- 16577177
TI  - ON THE IMPERFECTIONS OF CRYSTALS.

PMID- 16577179
TI  - THE CELL DIVISION AT WHICH CROSSING-OVER TAKES PLACE.

PMID- 16577178
TI  - THE MECHANISM OF SPARK DISCHARGE.

PMID- 16577180
TI  - AN UNEXPECTED ASSOCIATION OF FACTORS BELONGING TO THREE LINKAGE GROUPS IN
      OENOTHERA AND ITS EXPLANATION.

PMID- 16577181
TI  - AN INHERENT DEFECT IN THE THEORY THAT GROWTH RATE IS CONTROLLED BY AN
      AUTOCATALYTIC PROCESS.

PMID- 16577183
TI  - FUNCTIONAL DISTURBANCES OF HEARING IN GUINEA PIGS AFTER LONG EXPOSURE TO AN
      INTENSE TONE.

PMID- 16577182
TI  - CHLOROPHYLL CONTENT AND RATE OF PHOTOSYNTHESIS.

PMID- 16577184
TI  - STUDIES OF ORBITOIDAL FORAMINIFERA: THE SUBGENUS POLYLEPIDINA OF LEPIDOCYCLINA
      AND ORBITOCYCLINA, A NEW GENUS.

PMID- 16577185
TI  - PERTURBATIONS IN BAND SPECTRA. I.

PMID- 16577186
TI  - ON THE RAMAN EFFECT IN GASES.

PMID- 16577187
TI  - ABOUT THE PRODUCTION OF THE CONTINUOUS X-RAY SPECTRUM.

PMID- 16577188
TI  - THE RELATION BETWEEN THE ELECTRIC MOMENT AND THE POTENTIAL DIFFERENCE AT AN
      INTERFACE.

PMID- 16577189
TI  - ON THE CONTINUOUS SPECTRUM OF THE HYDROGEN ATOM.

PMID- 16577190
TI  - ON A FLUORESCENCE SPECTRUM OF OXYGEN.

PMID- 16577191
TI  - ON THE SPECTRA OF ZNII, CDII, INIII AND SNIV.

PMID- 16577192
TI  - POLARIZATION OF THE TUNGSTEN L RADIATIONS.

PMID- 16577193
TI  - A STUDY OF THE RAMAN EFFECT IN ACETONE.

PMID- 16577194
TI  - LINEAR TRANSFORMATIONS IN HILBERT SPACE: II. ANALYTICAL ASPECTS.

PMID- 16577196
TI  - MOMENTS OF MOMENTS.

PMID- 16577195
TI  - AGE CHANGES IN ALCOHOL TOLERANCE IN DROSOPHILA MELANOGASTER.

PMID- 16577197
TI  - METHODS OF RENDERING THE RUMEN AND RETICULUM OF RUMINANTS FREE FROM THEIR NORMAL
      INFUSORIAN FAUNA.

PMID- 16577198
TI  - MONATOMIC IODINE AND MOLECULAR HYDROGEN.

PMID- 16577200
TI  - PHOTOCHEMICAL TEMPERATURE COEFFICIENTS.

PMID- 16577201
TI  - THE OPALINDAE AND THEIR SIGNIFICANCE.

PMID- 16577199
TI  - THE DENSITY, COMPRESSIBILITY AND ATOMIC WEIGHT OF ARGON. II.

PMID- 16577202
TI  - THE RATE OF DECOMPOSITION OF NITROGEN PENTOXIDE AT MODERATELY LOW PRESSURE.

PMID- 16577203
TI  - TYPES OF UNIMOLECULAR REACTIONS.

PMID- 16577204
TI  - THE VALENCE OF SULFUR IN DITHIONATES.

PMID- 16577205
TI  - STUDIES ON THE GROWTH OF ROOT HAIRS IN SOLUTIONS. THE PH MOLAR RATE RELATION FOR
      BRASSICA OLERACEA IN CALCIUM SULPHATE.

PMID- 16577206
TI  - SOME NEW FEATURES OF THE ATMOSPHERIC OXYGEN BANDS, AND THE RELATIVE ABUNDANCE OF
      THE ISOTOPES O, O.

PMID- 16577207
TI  - FOSSIL PLANTS AND MOUNTAIN UPLIFT IN THE PACIFIC STATES.

PMID- 16577208
TI  - THE ANALYSIS OF A CONCRETE CASE OF INTERGRADATION BETWEEN TWO SUBSPECIES. II.
      ADDITIONAL DATA AND INTERPRETATIONS.

PMID- 16577209
TI  - ON THE LINEAR CONNECTION INDEX OF THE ALGEBRAIC SURFACES z = (fx, y).

PMID- 16577210
TI  - THE OCCURRENCE OF A NICOTIANA GLUTINOSA HAPLONT.

PMID- 16577211
TI  - FURTHER REMARKS CONCERNING THERMIONIC "A" AND "b," A REVISION AND EXTENSION.

PMID- 16577212
TI  - ON THE RAMAN EFFECT IN DIATOMIC GASES. II.

PMID- 16577213
TI  - ON THE THEORY OF ELECTRON SCATTERING IN GASES.

PMID- 16577214
TI  - MOLECULAR BINDING AND LOW S TERMS OF N AND C.

PMID- 16577215
TI  - WAVE-LENGTH OF THE K LINES OF COPPER USING RULED GRATINGS.

PMID- 16577217
TI  - A COMPARATIVE STUDY OF THE DIGESTION OF PROTEINS AND CARBOHYDRATES IN GOATS
      DURING INFUSORIA-FREE AND INFECTED PERIODS.

PMID- 16577216
TI  - EFFECT OF VOLUME CHANGES ON THE INFRA-RED VIBRATIONS OF SIMPLE CRYSTALS.

PMID- 16577218
TI  - THE MELANOPHORE ACTIVATOR OF THE EYE.

PMID- 16577219
TI  - THE RAMAN SPECTRUM OF GYPSUM.

PMID- 16577220
TI  - NOTE ON MR. KING'S PAPER: "THE CRYSTAL STRUCTURE OF STRONTIUM".

PMID- 16577221
TI  - RAMAN SPECTRA FROM ACETONE.

PMID- 16577222
TI  - THE THERMAL DECOMPOSITION OF ACETONE IN THE GASEOUS STATE.

PMID- 16577223
TI  - THE EQUILIBRIUM CONSTANTS OF REACTIONS INVOLVING HYDROXYL.

PMID- 16577224
TI  - ON THE CRYSTAL STRUCTURE OF THE CHLORIDES OF CERTAIN BIVALENT ELEMENTS.

PMID- 16577225
TI  - THE ELASTIC PROPERTIES OF CERTAIN BASIC ROCKS AND OF THEIR CONSTITUENT MINERALS.

PMID- 16577227
TI  - ON THE NUMBER OF CYCLIC SUBGROUPS OF A GROUP.

PMID- 16577226
TI  - THE MINIMA OF INDEFINITE QUATERNARY QUADRATIC FORMS.

PMID- 16577228
TI  - ON NEW INTEGRAL ADDITION THEOREMS FOR BESSEL FUNCTIONS.

PMID- 16577229
TI  - DWARF, A NEW MENDELIAN RECESSIVE CHARACTER OF THE HOUSE MOUSE.

PMID- 16577230
TI  - CRITERIA OF MALE AND FEMALE IN BREAD MOULDS (MUCORS).

PMID- 16577231
TI  - INFLUENCE OF ALUMINIUM ON MORTAR STRENGTH.

PMID- 16577233
TI  - PLANETARY MOTION IN A RETARDED NEWTONIAN POTENTIAL FIELD.

PMID- 16577232
TI  - ON THE JOINT INFLUENCE OF IRON AND ALUMINIUM IN NATIVE SANDS ON MORTAR STRENGTH.

PMID- 16577234
TI  - ON THE VIBRATIONAL SELECTION PRINCIPLES IN THE RAMAN EFFECT.

PMID- 16577235
TI  - ON THE APPLICATION OF THERMODYNAMICS TO THE THERMO-ELECTRIC CIRCUIT.

PMID- 16577236
TI  - ON THE NATURE OF THE TRANSVERSE THERMO-MAGNETIC EFFECT AND THE TRANSVERSE THERMO
      ELECTRIC EFFECT IN CRYSTALS.

PMID- 16577237
TI  - ON THE REDSHIFT OF SPECTRAL LINES THROUGH INTERSTELLAR SPACE.

PMID- 16577239
TI  - ON EINSTEIN'S UNIFIED FIELD EQUATIONS AND THE SCHWARZCHILD SOLUTION.

PMID- 16577238
TI  - RELATIVE INTENSITIES IN NUCLEAR SPIN MULTIPLETS.

PMID- 16577240
TI  - ELEMENTS IN THE SUN.

PMID- 16577241
TI  - BIOMETRIC FUNCTIONS IN A POPULATION GROWING IN ACCORDANCE WITH A PRESCRIBED LAW.

PMID- 16577242
TI  - BOUNDARY VALUES OF AN ANALYTIC FUNCTION AND THE TCHEBYCHEFF METHOD OF
      APPROXIMATION.

PMID- 16577244
TI  - ON MOSAIC CRYSTALS.

PMID- 16577243
TI  - ON THE POLARIZATION OF X-RADIATION.

PMID- 16577245
TI  - ON THE FOUNDATIONS OF RELATIVISTIC COSMOLOGY.

PMID- 16577246
TI  - PRODUCTION OF HYDROXYL BY WATER VAPOR DISCHARGE.

PMID- 16577247
TI  - A SPECTROPHOTOMETRIC STUDY OF CLASS A STARS.

PMID- 16577249
TI  - THE OCCURRENCE OF A HERITABLE TWISTED NOSE IN THE HOUSE MOUSE, MUS MUSCULUS.

PMID- 16577248
TI  - GENETIC FACTORS STIMULATING MUTABILITY OF THE MINIATURE-GAMMA WING CHARACTER OF
      DROSOPHILA VIRILIS.

PMID- 16577250
TI  - ON THE AMOUNT OF EXTERNAL MIRROR IMAGERY IN DOUBLE MONSTERS AND IDENTICAL TWINS.

PMID- 16577251
TI  - MEIOSIS IN A TRIPLOID FRAGARIA.

PMID- 16577252
TI  - CHROMOSOME BEHAVIOR IN SORBOPYRUS AND SORBARONIA.

PMID- 16577253
TI  - CHEMICAL ASPECTS OF DISEASE RESISTANCE IN THE ONION.

PMID- 16577254
TI  - ON THE EXISTENCE OF INTEGRALS OF THE SYSTEM OF PARTIAL DIFFERENTIAL EQUATIONS A =
      0 IN n VARIABLES.

PMID- 16577255
TI  - CLOSED EXTREMALS.

PMID- 16577256
TI  - NON-ABELIAN GROUPS OF ODD PRIME POWER ORDER WHICH ADMIT A MAXIMAL NUMBER OF
      INVERSE CORRESPONDENCIES IN AN AUTOMORPHISM.

PMID- 16577257
TI  - The Light-Sensitive System as the Basis of the Photic Responses of Phycomyces.

PMID- 16577259
TI  - Crystal Structures of Some Derivatives of Diphenyl.

PMID- 16577258
TI  - A New Equation of State for Fluids: IV. An Equation Expressing the Volume as an
      Explicit Function of the Pressure and Temperature.

PMID- 16577260
TI  - The Temperature Coefficient of the Photochemical Formation of Hydrogen Chloride.

PMID- 16577261
TI  - Ozone in Luminescence.

PMID- 16577263
TI  - Recent Progress in the Dual Theory of Metallic Conduction.

PMID- 16577262
TI  - Geometrical Optics in Absorbing Media.

PMID- 16577264
TI  - Two Contradictions in Current Physical Theory and Their Resolution.

PMID- 16577265
TI  - The Rate of Decomposition of Nitrogen Pentoxide at Very Low Pressures.

PMID- 16577267
TI  - The Distribution of Light Intensity in a Fresnel Diffraction Pattern from a
      Straight Edge.

PMID- 16577266
TI  - Theoretical Interpretation of Hyper-Fine-Structure in Singly Ionized Thallium, Tl
      II.

PMID- 16577268
TI  - Note on Range-Finding.

PMID- 16577269
TI  - Applications of an Expansion Theorem to the Development of the Disturbing
      Function.

PMID- 16577271
TI  - Groups Which Admit Two-Thirds Automorphisms.

PMID- 16577270
TI  - On Certain Polynomial and Other Approximations to Analytic Functions.

PMID- 16577272
TI  - Differential Geometries of Function Space.

PMID- 16577273
TI  - THE STRUCTURE OF SOME SODIUM AND CALCIUM ALUMINOSILICATES.

PMID- 16577274
TI  - THE DEMONSTRATION THAT ALLERGIC INFLAMMATION IS NOT NECESSARY FOR THE OPERATION
      OF ACQUIRED IMMUNITY.

PMID- 16577275
TI  - ON THE SYSTEMATIC AND ACCIDENTAL ERRORS OF MODERN TRIGONOMETRIC PARALLAXES.

PMID- 16577276
TI  - ON THE DISTANCES AND RADIAL VELOCITIES OF EXTRA-GALACTIC NEBULAE, AND THE
      EXPLANATION OF THE LATTER BY THE RELATIVITY THEORY OF INERTIA.

PMID- 16577277
TI  - THE CELLULAR DIVISION AND APPROXIMATION OF REGULAR SPREADS.

PMID- 16577278
TI  - NORMAL COORDINATES IN THE GEOMETRY OF PATHS.

PMID- 16577279
TI  - THE CRYSTAL CLOCK.

PMID- 16577280
TI  - THE BAND SPECTRUM OF OZONE IN THE VISIBLE AND PHOTOGRAPHIC INFRA-RED.

PMID- 16577281
TI  - ON THE ESTIMATION OF DISTANCES IN A CURVED UNIVERSE WITH A NON-STATIC LINE
      ELEMENT.

PMID- 16577282
TI  - EXPERIMENTS IN BIRD MIGRATION. II. REVERSED MIGRATION.

PMID- 16577284
TI  - THE STRUCTURAL BASIS OF THE INTEGRATION OF BEHAVIOR.

PMID- 16577283
TI  - REFLECTION OF WAVES IN AN INHOMOGENEOUS ABSORBING MEDIUM.

PMID- 16577285
TI  - LOCALIZATION OF FUNCTION IN THE NERVOUS SYSTEM.

PMID- 16577286
TI  - GLYCOGEN METABOLISM.

PMID- 16577287
TI  - NOTE ON THE NATURE OF COSMIC RAYS.

PMID- 16577288
TI  - PERIODICITY IN SEQUENCES DEFINED BY LINEAR RECURRENCE RELATIONS.

PMID- 16577289
TI  - THE STRESS DISTRIBUTION IN WELDS.

PMID- 16577290
TI  - THE STRESS DISTRIBUTION IN WELDED OVERLAPPED JOINTS.

PMID- 16577293
TI  - THE HEAT OF FORMATION OF WATER.

PMID- 16577291
TI  - A RADIO SYSTEM FOR BLIND LANDING OF AIRCRAFT IN FOG.

PMID- 16577292
TI  - A SENSITIVE INDUCTION BALANCE FOR THE PURPOSE OF DETECTING UNEXPLODED BOMBS.

PMID- 16577294
TI  - CRYSTALLINE ALPHA AND BETA METHYL-d-GULOSIDES.

PMID- 16577295
TI  - THE RING STRUCTURE OF MANNOSE.

PMID- 16577296
TI  - NON-DISJUNCTION OF THE X-CHROMOSOME IN DROSOPHILA VIRILIS.

PMID- 16577297
TI  - RELATION BETWEEN THE X-RAY DOSAGE AND THE FREQUENCY OF PRIMARY NON-DISJUNCTIONS
      OF X-CHROMOSOMES IN DROSOPHILA VIRILIS.

PMID- 16577298
TI  - RECOVERY FOLLOWING GENETIC DEFICIENCY IN MAIZE.

PMID- 16577299
TI  - MAGNETIC ANALYSIS OF NEGATIVE IONS IN MERCURY VAPOR.

PMID- 16577300
TI  - THE PRESSURE OF THE WIND ON LARGE CHIMNEYS.

PMID- 16577301
TI  - PROJECTIVE NORMAL COORDINATES.

PMID- 16577302
TI  - ON THE NORM-RESIDUE SYMBOL IN THE THEORY OF CYCLOTOMIC FIELDS.

PMID- 16577303
TI  - ON THE SECOND FACTOR OF THE CLASS NUMBER OF A CYCLOTOMIC FIELD.

PMID- 16577304
TI  - PERIODIC RECURRING SERIES.

PMID- 16577305
TI  - NOTE ON SINGULARITIES OF POWER SERIES.

PMID- 16577306
TI  - A METHOD OF OBTAINING NORMAL REPRESENTATIONS FOR A PROJECTIVE CONNECTION.

PMID- 16577307
TI  - ON THE UNIFIED FIELD THEORY. I.

PMID- 16577308
TI  - THE CRITICAL POINTS OF A FUNCTION OF n VARIABLES.

PMID- 16577309
TI  - BIOTIC CEMENTATION IN CORAL REEFS.

PMID- 16577310
TI  - THE QUANTITATIVE THEORY OF SEX AND THE GENETIC CHARACTER OF HAPLOID MALES.

PMID- 16577311
TI  - A CYTOLOGICAL DEMONSTRATION OF THE LOCATION OF AN INTERCHANGE BETWEEN TWO NON
      HOMOLOGOUS CHROMOSOMES OF ZEA MAYS.

PMID- 16577312
TI  - THE INHERITANCE OF RUBRICALYX BUD COLOR IN CROSSES WITH OENOTHERA LAMARCKIANA.

PMID- 16577313
TI  - COMPLETE ELIMINATION OF SELF-STERILITY IN THE ASCIDIAN STYELA BY FERTILIZING IN
      ALKALINE SOLUTIONS.

PMID- 16577314
TI  - THE AMMONIA DISCHARGE TUBE.

PMID- 16577315
TI  - THE SEPARATION OF THE TWO TYPES OF IODINE MOLECULE AND THE PHOTOCHEMICAL REACTION
      OF GASEOUS IODINE WITH HEXENE.

PMID- 16577317
TI  - ON THE INTENSITY OF TOTAL SCATTERING OF X-RAYS BY MONATOMIC GASES.

PMID- 16577318
TI  - IRROTATIONAL MOTION OF A COMPRESSIBLE INVISCID FLUID.

PMID- 16577316
TI  - NOTE ON THE EQUATION OF STATE EXPLICIT IN THE VOLUME.

PMID- 16577319
TI  - A STUDY OF INDEFINITELY DIFFERENTIABLE AND QUASI-ANALYTIC FUNCTIONS.

PMID- 16577320
TI  - ON THE UNIFIED FIELD THEORY. II.

PMID- 16577321
TI  - The Penetration of 1-Naphthol-2-Sulphonate Indophenol, o-Chloro Phenol Indophenol
      and o-Cresol Indophenol into Valonia.

PMID- 16577322
TI  - The Energy Cost of the Excretion of Urine.

PMID- 16577323
TI  - The Thermal Decomposition of Nitrogen Pentoxide at Low Pressures.

PMID- 16577324
TI  - The Work of the Kidney in the Production of Urine.

PMID- 16577325
TI  - On the Transfer of Energy between Atoms at Collision.

PMID- 16577326
TI  - Groups Which Admit Five-Eighths Automorphisms.

PMID- 16577327
TI  - Multivectorial Curvature.

PMID- 16577328
TI  - On the Unified Field Theory: III.

PMID- 16577329
TI  - Quantum-Mechanical Motion of Free Electrons in Electromagnetic Fields.

PMID- 16577330
TI  - Remarks on a Paper: Note on the Nature of Cosmic Rays, by Paul S. Epstein.

PMID- 16577331
TI  - The Production of High Speed Canal Rays without the Use of High Voltages.

PMID- 16577332
TI  - On the Interpretation of Dirac's alpha-Matrices.

PMID- 16577333
TI  - Reactions of Dermal Melanophores in Necturus to Heat and to Cold.

PMID- 16577334
TI  - Histological Polarization of Lateral Giant-Fibres in the Crayfish.

PMID- 16577335
TI  - On the Groups of Orientable Two-Manifolds.

PMID- 16577336
TI  - Inverse Commutator Subgroups.

PMID- 16577337
TI  - The Convention of Equidimensional Electric and Magnetic Units.

PMID- 16577338
TI  - On Thermodynamic Equilibrium in a Static Einstein Universe.

PMID- 16577339
TI  - Answer to Prof. Stormer's Remark.

PMID- 16577340
TI  - I. The Reaction to Posterior Pituitary Extract (Pituitrin) When Introduced into
      the Cerebral Ventricles.

PMID- 16577342
TI  - III. The Action of Atropine in Counteracting the Effects of Pituitrin and of
      Pilocarpine Injected into the Cerebral Ventricles.

PMID- 16577341
TI  - II. The Similarity in the Response to Posterior Lobe Extract (Pituitrin) and to
      Pilocarpine When Injected into the Cerebral Ventricles.

PMID- 16577343
TI  - Activation by Charcoal.

PMID- 16577344
TI  - Aromatic Substitution Products with Fluorine.

PMID- 16577345
TI  - Reversible Coagulation in Living Tissue: II.

PMID- 16577346
TI  - Movement of the So-Called Hairs in the Ampullar Organs of Fish Ears.

PMID- 16577347
TI  - Further Observations on the Nature of the X-Prime (X') Chromosome in Sciara.

PMID- 16577348
TI  - On the Unifield Field Theory: V.

PMID- 16577349
TI  - The Least Area Property of the Minimal Surface Determined by an Arbitrary Jordan
      Contour.

PMID- 16577351
TI  - The Composition of the Interior of the Earth.

PMID- 16577350
TI  - Function Space-Time Manifolds.

PMID- 16577352
TI  - Rotational Raman Spectrum of CO(2).

PMID- 16577353
TI  - Accuracy in Percentage Representation of Heavy Mineral Frequencies.

PMID- 16577354
TI  - IV. The Method of Action of Pituitrin Introduced into the Ventricle.

PMID- 16577355
TI  - V. The Counteractive Effect of Tribromethanol (Avertin) on the Stimulatory
      Response to Pituitrin Injected in the Ventricle.

PMID- 16577356
TI  - VI. Concerning a Possible "Parasympathetic Center" in the Diencephalon.

PMID- 16577357
TI  - The Inadequacy of the Sub-Gene Hypothesis of the Nature of the Scute Allelomorphs
      of Drosophila.

PMID- 16577359
TI  - Differences between Chromosome Groups of Soma and Germ-Line in Sciara.

PMID- 16577358
TI  - Proof That Bar Changes to Not-Bar by Unequal Crossing-Over.

PMID- 16577360
TI  - The Hereditary Basis for Melanosis in Hybrids of Mexican Killifishes.

PMID- 16577361
TI  - The Responses of the Deep-Seated Melanophores in the Frog to Adrenalin and
      Pituitrin.

PMID- 16577362
TI  - Control of Pigment Migration in the Chromatophores of Crustaceans.

PMID- 16577363
TI  - The Correlation between Tanning and Unexposed Skin Color as Recorded by the Color
      Top.

PMID- 16577365
TI  - Reversible Coagulation in Living Tissue: III.

PMID- 16577364
TI  - Studies on Electrokinetic Potentials: IX. The Electrical Field of Force at Liquid
      liquid Interfaces.

PMID- 16577366
TI  - A Critique of Recent Quantum Theories.

PMID- 16577367
TI  - Dissipative Dynamical Systems: I.

PMID- 16577369
TI  - The Order of Vanishing of the Determinant of a Conjugate Base.

PMID- 16577368
TI  - Hamiltonian Systems and Transformation in Hilbert Space.

PMID- 16577370
TI  - Automorphisms of Order 2 of an Abelian Group.

PMID- 16577371
TI  - On the Unified Field Theory: VI.

PMID- 16577372
TI  - Optical Sensitization.

PMID- 16577373
TI  - Reversible Coagulation in Living Tissue: IV.

PMID- 16577374
TI  - The Cupula of the Ear.

PMID- 16577375
TI  - The Cilia of Naphthys Bucera.

PMID- 16577376
TI  - A Canonical Form for Real Matrices under Orthogonal Transformations.

PMID- 16577377
TI  - Wave Motion and the Equation of Continuity.

PMID- 16577378
TI  - Electric Conductivity and Optical Absorption in Metals (Supplementary).

PMID- 16577380
TI  - Uncomplicated Trisomic Inheritance of Purple Versus Red in Matthiola.

PMID- 16577379
TI  - Electromagnetic Fields Derived from Non-Commuting Potentials.

PMID- 16577381
TI  - The Probable Origin of Oenothera Rubricalyx "Afterglow" on the Basis of the
      Segmental Interchange Theory.

PMID- 16577382
TI  - Inheritance of Body Weight in Domestic Fowl.

PMID- 16577383
TI  - A Set of Axioms for Differential Geometry.

PMID- 16577384
TI  - Solutions of a Certain Partial Differential Equation.

PMID- 16577385
TI  - A Synthesis of the Theorems of Hadamard and Hurwitz on Composition of
      Singularities.

PMID- 16577386
TI  - Reversible Coagulation in Living Tissue: VI.

PMID- 16577387
TI  - Reversible Coagulation in Living Tissue: VII.

PMID- 16577388
TI  - Radioactive Disintegration.

PMID- 16577389
TI  - Body Temperature and Heat Regulation of Large Snakes.

PMID- 16577390
TI  - Progressive Degeneration of the Lateral-Line Nerve in the Catfish.

PMID- 16577391
TI  - The Relation of Taste-Buds to Their Nerve-Fibres.

PMID- 16577392
TI  - The Color Changes in the Sea-Urchin Arbacia.

PMID- 16577393
TI  - Effects of Acetyl Choline on Chromatophores.

PMID- 16577394
TI  - Reversible Coagulation in Living Tissue: VIII.

PMID- 16577395
TI  - Crossing-Over and Mutation.

PMID- 16577396
TI  - A Preliminary Report on Functional Psychoses.

PMID- 16577397
TI  - The Heating of Liquids by the Absorption of Sound, and Its Relation to the Energy
      of Intense High-Frequency Sound Waves.

PMID- 16577398
TI  - The Crystal Lattice of Calcium Metaborate, CaB(2)O(4).

PMID- 16577399
TI  - A Search for an Electrostatic Analog to the Gravitational Red Shift.

PMID- 16577400
TI  - The Natural History of the Vibrato.

PMID- 16577401
TI  - Measures of Certain Human Abilities throughout the Life Span.

PMID- 16577402
TI  - The Use of Rock Crystal by Paleolithic Man.

PMID- 16577403
TI  - Reversible Coagulation in Living Tissue: IX.

PMID- 16577404
TI  - Further Properties of Abelian Integrals Attached to Algebraic Varieties.

PMID- 16577405
TI  - Proof of a Recurrence Theorem for Strongly Transitive Systems.

PMID- 16577406
TI  - Proof of the Ergodic Theorem.

PMID- 16577407
TI  - Summary of Results and Proofs on Fermat's Last Theorem. (Sixth Paper).

PMID- 16577408
TI  - Properties of Group Manifolds.

PMID- 16577409
TI  - On a Polar Representation of Non-Singular Square Matrices.

PMID- 16577410
TI  - Note on the Heaviside Expansion Formula.

PMID- 16577411
TI  - The Distribution of Chi-Square.

PMID- 16577412
TI  - Relations between Confluent Hypergeometric Functions.

PMID- 16577413
TI  - Groups Involving a Small Number of Conjugates.

PMID- 16577414
TI  - Linkage Values in an Interchange Complex in Zea.

PMID- 16577415
TI  - Modification of Mendelian Ratios in Maize by Mechanical Separation of Gametes.

PMID- 16577416
TI  - A Probable New Mutation to White-Belly in the House Mouse, Mus Musculus.

PMID- 16577417
TI  - The Gompertz Curve as a Growth Curve.

PMID- 16577418
TI  - Sets of Distinct Group Operators Involving All the Products but Not All the
      Squares.

PMID- 16577419
TI  - Conformal Tensors. (First Note.).

PMID- 16577420
TI  - On the Changes of Sign of the Derivatives of a Function Defined by a Laplace
      Integral.

PMID- 16577422
TI  - Genetics of Sensory Thresholds: Taste for Phenyl Thio Carbamide.

PMID- 16577421
TI  - The Relationship between Chemical Constitution and Taste.

PMID- 16577423
TI  - Elimination of Self-Sterility in the Styela Egg-A Re-Interpretation with Further
      Experiments.

PMID- 16577424
TI  - The Physiological Effect of Trihydrol in Water.

PMID- 16577425
TI  - The Arizona Expedition for the Study of Meteors.

PMID- 16577427
TI  - Studies on the Growth Hormone of Plants: I.

PMID- 16577426
TI  - The Growth of Scenedesmus Acutus.

PMID- 16577428
TI  - The Basis of the Dependence of Visual Acuity on Illumination.

PMID- 16577429
TI  - Quantum Dynamical Correction for the Equation of State of Real Gases.

PMID- 16577432
TI  - Proof of the Quasi-Ergodic Hypothesis.

PMID- 16577430
TI  - New Lines in the K Series of X-Rays.

PMID- 16577431
TI  - Note on Perron's Solution of the Dirichlet Problem.

PMID- 16577433
TI  - Reversible Coagulation in Living Tissue: X.

PMID- 16577434
TI  - Seven Theorems in the Problem of Plateau.

PMID- 16577435
TI  - On Combinatorial Topology.

PMID- 16577436
TI  - Lines of Julia of Integral Functions.

PMID- 16577437
TI  - On the Time Average Theorem in Dynamics.

PMID- 16577438
TI  - The Developmental Morphology of Infant Behavior Pattern.

PMID- 16577440
TI  - The Fading of Lakes and Dyed Fibres.

PMID- 16577439
TI  - Allotropy of Liquid Benzene.

PMID- 16577441
TI  - Cytology of the Ferox-Quercifolia-Stramonium Triangle in Datura.

PMID- 16577442
TI  - A Possible Influence of the Spindle Fibre on Crossing-Over in Drosophila.

PMID- 16577443
TI  - An Expansion of Meromorphic Functions.

PMID- 16577444
TI  - Contribution to the Mathematical Theory of Capture: I. Conditions for Capture.

PMID- 16577445
TI  - A New Set of Independent Postulates for the Algebra of Logic with Special
      Reference to Whitehead and Russell's Principia Mathematica.

PMID- 16577447
TI  - On the Unitary Invariants of a Square Matrix.

PMID- 16577446
TI  - Preliminary Note on the Inversion of the Laplace Integral.

PMID- 16577448
TI  - Conformal Tensors. (Second Note.).

PMID- 16577449
TI  - Intransitive Groups of Motions.

PMID- 16577450
TI  - On Certain Properties of Separable Spaces.

PMID- 16577451
TI  - Complete Transitivity and the Ergodic Principle.

PMID- 16577452
TI  - The Incubating Python: A Temperature Study.

PMID- 16577453
TI  - The Genetic Demonstration of Double Strand Crossing-Over in Zea Mays.

PMID- 16577455
TI  - Stratigraphical Research in Central Mexico.

PMID- 16577454
TI  - The Behavior of Vermilion-Suppressor in Mosaics.

PMID- 16577456
TI  - Isovioluric Acid (Alloxan-6-Oxime).

PMID- 16577457
TI  - Concentration of the H Isotope of Hydrogen by the Fractional Electrolysis of
      Water.

PMID- 16577458
TI  - The Electronic Structure of the Normal Nitrous Oxide Molecule.

PMID- 16577460
TI  - Orders for Which There Exist Exactly Four or Five Groups.

PMID- 16577459
TI  - Further Concerning a Parasympathetic Center in the Interbrain: VII. The Effect of
      Intraventricularly-Injected Histamine.

PMID- 16577461
TI  - On Interpolation to Harmonic Functions by Harmonic Polynomials.

PMID- 16577462
TI  - Partial Differentiation in the Large.

PMID- 16577463
TI  - Eocene Land Mammals of the Pacific Coast.

PMID- 16577465
TI  - A Search for Evidence of the Radioactive Decomposition of Barium.

PMID- 16577466
TI  - The Reaction of Chlorine with Hydrogen.

PMID- 16577464
TI  - Absence of Corpus Callosum, a Hereditary Brain Anomaly of the House Mouse.
      Preliminary Report.

PMID- 16577467
TI  - An Investigation of Intermediate Compound Formation by Means of the Raman Effect.

PMID- 16577469
TI  - Neuro-Humoral Control of Fish Melanophores.

PMID- 16577468
TI  - Double Innervation of Melanophores.

PMID- 16577470
TI  - Gamma Radiation.

PMID- 16577471
TI  - An Upper Oligocene Mammalian Fauna from Southern California.

PMID- 16577472
TI  - An Extension of the New Einstein Geometry.

PMID- 16577473
TI  - Simultaneous Differential Invariants of an Affine Connection and a General Linear
      Connection.

PMID- 16577474
TI  - The Standard Error of a Tetrad in Samples from a Normal Population of Independent
      Variables.

PMID- 16577475
TI  - The Vapor Pressure of Liquid Water That Has Recently Been Frozen.

PMID- 16577476
TI  - The Origin of the Landlocked Habit in Salmon.

PMID- 16577477
TI  - The Importance of the Time Element in the Determination of the Respiratory
      Metabolism of Fishes.

PMID- 16577478
TI  - Thermal Doppler Effect and Turbulence in Stellar Spectra of Early Class.

PMID- 16577479
TI  - On the Intensities of Stellar Absorption Lines.

PMID- 16577481
TI  - Non-Group Operations.

PMID- 16577480
TI  - Note on the Divisors of the Numerators of Bernoulli's Numbers.

PMID- 16577482
TI  - On Representation of Integers by Quadratic Forms.

PMID- 16577483
TI  - The Foraminiferal Genus Orbitolina in Guatemala and Venezuela.

PMID- 16577484
TI  - Cretaceous Orbitoidal Formanifera from the Gulf States and Central America.

PMID- 16577485
TI  - Structure and Correlation of Metamorphic Rocks in Southeastern New York.

PMID- 16577486
TI  - Chromosome Rings on Oenothera, Drosophila and Maize.

PMID- 16577487
TI  - Xanthophores in Fundulus, with Special Consideration of Their "Expanded" and
      "Contracted" Phases.

PMID- 16577488
TI  - Experiments in Bird Migration: III. The Effects of Artificial Light, Castration
      and Certain Extracts on the Autumn Movements of the American Crow(Corvus
      brachyrhynchis).

PMID- 16577489
TI  - Hydrocephalus, a Hereditary Character in the House Mouse.

PMID- 16577491
TI  - Glacial Epochs of the Santa Monica Mountains, California.

PMID- 16577490
TI  - Rate of Instability of Miniature-3 Gamma Gene of Drosophila Virilis in the Males
      in the Homozygous and in the Heterozygous Females.

PMID- 16577492
TI  - The Commutator Subgroup of a Group Generated by Two Operators.

PMID- 16577493
TI  - On the Distributions of the Zeros of Certain Analytic Functions.

PMID- 16577494
TI  - On the Behavior of the nth Iterate of a Fredholm Kernel as n Becomes Infinite.

PMID- 16577495
TI  - On the Function in Quantum Mechanics Which Corresponds to a Given Function in
      Classical Mechanics.

PMID- 16577496
TI  - A Correlation of Ring-Shaped Chromosomes with Variegation in Zea Mays.

PMID- 16577498
TI  - The Crustacean Chromatophore Activator and the Gonads of the Rat.

PMID- 16577497
TI  - Critical Torsional Oscillations of a Rotating Accerated shaft.

PMID- 16577499
TI  - The Penetration of m-Bromo-Phenol Indophenol and of Guaiacol Indophenol into
      Valonia Ventricosa.

PMID- 16577500
TI  - Studies on the Growth Hormone of Plants: II. The Entry of Growth Substance into
      the Plant.

PMID- 16577501
TI  - Impulses from Sensory Nerves of Catfish.

PMID- 16577502
TI  - Accommodation Coefficient of Gaseous Ions at Cathodes.

PMID- 16577503
TI  - Recurrent Geodesics on Any Closed Orientable Surface of Genus One.

PMID- 16577504
TI  - The General Case of Integro-Q-Difference Equations.

PMID- 16577505
TI  - A Property of Indefinitely Differentiable Classes.

PMID- 16577507
TI  - A Characterization of Fields in the Calculus of Variations.

PMID- 16577506
TI  - Operators of Order p in the Group of Isomorphisms of the Abelian Group of Order p
      and Type 1,1,..

PMID- 16577508
TI  - The Space Motions of Stars in the Orion and Scorpio-Centaurus Clusters.

PMID- 16577509
TI  - The Penetration of Iron Meteorites into the Ground.

PMID- 16577510
TI  - Trimethyl Gallium, Trimethyl Gallium Etherate and Trimethyl Gallium Ammine.

PMID- 16577511
TI  - Chlorination Products of Trimethyl Gallium.

PMID- 16577512
TI  - The Three-Electron Bond in Chlorine Dioxide.

PMID- 16577513
TI  - The Neutron, Atom Building and a Nuclear Exclusion Principle.

PMID- 16577514
TI  - Biological Significance of Protective Mechanisms Inherent in the Myocardium.

PMID- 16577515
TI  - Metachronism in Ciliated Epithelium.

PMID- 16577516
TI  - The Intracellular Fibre Systems of Paramecium.

PMID- 16577517
TI  - The Controlling Mechanism of Chromatophores in Palaemonetes.

PMID- 16577518
TI  - Degeneration of Melanophores in Fundulus.

PMID- 16577519
TI  - Groups in Which Either All the Operators or All the Subgroups of the Same Order
      Are Conjugate.

PMID- 16577520
TI  - An Extremely Simple Method of Periodogram Analysis.

PMID- 16577521
TI  - Some Remarks Concerning Schrodinger's Wave Equation.

PMID- 16577522
TI  - On the Measure of the Non-Special Geodesics on a Surface of Constant Negative
      Curvature.

PMID- 16577523
TI  - I. Introductory Remarks.

PMID- 16577524
TI  - II. Evidences of Cycles in Tree Ring Records.

PMID- 16577525
TI  - III. Periodicity in Solar Variation.

PMID- 16577526
TI  - IV. The Nature of the Solar Cycle.

PMID- 16577527
TI  - V. Correlation of Sedimentary and Climatic Records.

PMID- 16577528
TI  - On the Distribution of Galaxies.

PMID- 16577529
TI  - Influence of Intensive Desiccation on Certain Physical Properties of Benzene.

PMID- 16577530
TI  - On the Sterility of the Interracial Hybrids in Drosophila Pseudoobscura.

PMID- 16577531
TI  - A Further Study of Blood Groups of the Rabbit.

PMID- 16577532
TI  - Inbreeding and Homozygosis.

PMID- 16577533
TI  - Inbreeding and Recombination.

PMID- 16577534
TI  - Hyaenodontidae of the Upper Eocene of California.

PMID- 16577535
TI  - The Effect of Helium on the Continuous and Secondary Spectra of Hydrogen.

PMID- 16577536
TI  - K Series Spectrum of Tungsten.

PMID- 16577537
TI  - An Analytic Closed Space Curve Which Bounds No Orientable Surface of Finite Area.

PMID- 16577538
TI  - Regular Differential Systems of the First Order.

PMID- 16577539
TI  - Note on a Metrically Transitive System.

PMID- 16577540
TI  - Application of Poincare's Sweeping-Out Process.

PMID- 16577541
TI  - Geometry of Two-Component Spinors.

PMID- 16577542
TI  - On the Interpretation of Nova Spectra.

PMID- 16577543
TI  - Chromosome Number and Morphology in Nicotiana VI: Chromosome Numbers of Forty
      Species.

PMID- 16577544
TI  - Young's Modulus and Poisson's Ratio with Reference to Geophysical Applications.

PMID- 16577545
TI  - Compressibility and Anisotropy of Rocks at and near the Earth's Surface.

PMID- 16577546
TI  - Comparison of the Statically and Seismologically Determined Elastic Constants of
      Rocks.

PMID- 16577547
TI  - The General Case of Non-Homogeneous Linear Differential Equations.

PMID- 16577549
TI  - On a Theorem of Fejer.

PMID- 16577548
TI  - A Canonical Form for a Set of Vectors.

PMID- 16577550
TI  - Aristogenesis, the Observed Order of Biomechanical Evolution.

PMID- 16577551
TI  - Electrosmosis and Anomalous Osmosis.

PMID- 16577552
TI  - Note on the Sturm-Liouville Eigenvalue-Eigenfunction Problem with Singular End
      Points.

PMID- 16577553
TI  - Studies on the Growth Hormone of Plants: III. The Inhibiting Action of the Growth
      Substance on Bud Development.

PMID- 16577554
TI  - Studies on the Growth Hormone of Plants: IV. On the Mechanism of the Action.

PMID- 16577555
TI  - The Energy of Urea Synthesis: II. The Effect of Varying Hydrogen Ion
      Concentration with Different Metabolites.

PMID- 16577556
TI  - On the Temperature-Regulatory Function of "Spontaneous" Activity in the Mouse.

PMID- 16577557
TI  - The Development of Temperature Regulation in the Mouse.

PMID- 16577558
TI  - The Influence of Use or Frequency of Occurrence upon the Strength of Mental
      Connections.

PMID- 16577559
TI  - The Effects of the Pituitary Hormones on the Melanophores of Fishes.

PMID- 16577560
TI  - The Occurrence of Guanophores in Fundulus.

PMID- 16577561
TI  - Photic Stimulation and Rhythmical Contractions of the Mantle Flaps of a
      Lamellibranch.

PMID- 16577562
TI  - The Photochemical Production of Triphenylmethyl.

PMID- 16577564
TI  - On the Invariance of General Intelligence.

PMID- 16577563
TI  - An Amynodont Skull from the Sespe Deposits, California.

PMID- 16577565
TI  - Retinal Rivalry as a Neglected Factor in Stereoscopic Vision.

PMID- 16577566
TI  - Contact Potential Differences between Different Faces of Copper Single Crystals.

PMID- 16577567
TI  - Number of Operators of Prime Power Orders Contained in a Group.

PMID- 16577569
TI  - The General Formula of Heredity.

PMID- 16577568
TI  - Evidences of Man's Ancestral History in the Later Development of the Child.

PMID- 16577570
TI  - A Tree-Ring Chronology for the Rio Grande Drainage in Northern New Mexico.

PMID- 16577571
TI  - Some Observations on the Archean Metamorphics of the Grand Canyon.

PMID- 16577572
TI  - A Preliminary Survey of the Species of Zostera.

PMID- 16577573
TI  - Remarks on Superconductivity.

PMID- 16577574
TI  - Concentration and Purification of a Growth Inhibitor Extracted from Kidney: A
      Preliminary Report.

PMID- 16577575
TI  - The Abolishment of a Discrimination.

PMID- 16577576
TI  - Crystallization of a Compound of Hemoglobin and Carbon Dioxide.

PMID- 16577577
TI  - Interchange between X- and Y-Chromosomes in Attached X Females of Drosophila
      Melanogaster.

PMID- 16577578
TI  - Pollen Tube Establishment and the Deficiency of Waxy Seeds in Certain Maize
      Crosses.

PMID- 16577579
TI  - The Effect of Homozygous Genes for Self-Sterility.

PMID- 16577580
TI  - On Criteria for Fourier Constants of L Integrable Functions.

PMID- 16577581
TI  - Groups Whose Operators Have No More Than Three Distinct Squares.

PMID- 16577582
TI  - Logarithmic Solutions of Bianchi's Equation.

PMID- 16577583
TI  - Urease Activity as Influenced by Oxidation and Reduction.

PMID- 16577584
TI  - The Electron-Diffraction Investigation of the Structure of Molecules of Methyl
      Azide and Carbon Suboxide.

PMID- 16577586
TI  - Oxidation-Reduction Potential of Ascorbic Acid (Vitamin C).

PMID- 16577585
TI  - The Electron-Diffraction Investigation of the Molecular Structure of Cyanogen and
      Diacetylene (with a Note on Chlorine Dioxide).

PMID- 16577587
TI  - The Dielectric Properties of Solutions of Electrolytes in a Non-Polar Solvent.

PMID- 16577588
TI  - The Purification and Physical Properties of Chemical Compounds: IV. A Development
      of a Theoretical Basis for the Behavior of Controlled Time-Temperature Curves.

PMID- 16577590
TI  - Role of the Autosomes in the Drosophila Pseudoobscura Hybrids.

PMID- 16577589
TI  - The Linkage Relations of Yellow Fat in Rabbits.

PMID- 16577591
TI  - An Eocene Primate from California.

PMID- 16577592
TI  - Note on Polynomial Interpolation to Analytic Functions.

PMID- 16577593
TI  - The Influence of Intensity on the Visual Functions of Drosophila.

PMID- 16577595
TI  - Spinors in Projective Relativity.

PMID- 16577594
TI  - The Relationships of Scrapter, a Genus of African Bees.

PMID- 16577596
TI  - Fused "Onium" Salts as Acids: I. Reactions in Fused Ammonium Nitrate.

PMID- 16577597
TI  - Norms of Pollen-Tube Growth in Incompatible Matings of Self-Sterile Plants.

PMID- 16577599
TI  - Projective Differentiation of Spinors.

PMID- 16577598
TI  - A New Gene Affecting Behavior and Skeleton in the House Mouse.

PMID- 16577600
TI  - The Extinction of Chained Reflexes.

PMID- 16577601
TI  - Anomalies in the Absorption Spectrum of Visual Purple.

PMID- 16577602
TI  - Groups Involving Three and Only Three Squares.

PMID- 16577603
TI  - Heterotopic Spinal Cord Grafts in Salamander Embryos.

PMID- 16577605
TI  - A Preliminary Revision of the Perennial Species of Eriophyllum.

PMID- 16577604
TI  - On Photosynthesis and Free Nitrogen Assimilation by Leguminous Plants.

PMID- 16577606
TI  - Observations upon Growth from the Viewpoint of Statistical Interpretation.

PMID- 16577608
TI  - The Absence of Otonomy in the Development of the Effects of Certain Deficiencies
      in Drosophila melanogaster.

PMID- 16577607
TI  - A Spectrographic Study of the Occurrence of Chromium and Molybdenum in Carcinoma
      of the Human Breast.

PMID- 16577609
TI  - New Creodonta from the Sespe Upper Eocene, California.

PMID- 16577610
TI  - A Note on Cremonia Transformations.

PMID- 16577611
TI  - Distinct Groups Whose Subgroups Are Simply Isomorphic.

PMID- 16577612
TI  - Locally Compact Abelian Groups.

PMID- 16577613
TI  - Suggestions as to the Energy-Momentum Principle in a Non-Conservative Mechanics.

PMID- 16577614
TI  - Suggestions as to Metric in a Non-Conservative Mechanics.

PMID- 16577617
TI  - The Attributes of Tones.

PMID- 16577615
TI  - The Temperature-Structure-Composition Behavior of Certain Crystals.

PMID- 16577616
TI  - The Production of the Crustacean Chromatophore Activator.

PMID- 16577618
TI  - Proposal of a Method of Observing the Solar Corona without an Eclipse.

PMID- 16577619
TI  - The Influence of Pregnancy upon the Titre of Immune (Blood Group) Antibodies in
      the Rabbit.

PMID- 16577621
TI  - The Spectral Sensibility of Avena.

PMID- 16577620
TI  - Radioactivity Artificially Induced by Neutron Bombardment.

PMID- 16577622
TI  - Further Experiments on the Inhibition of the Development of Lateral Buds by
      Growth Hormone.

PMID- 16577623
TI  - The Potential of a Positive Mass and the Weight Function of Wiener.

PMID- 16577624
TI  - V(3) IN V(6).

PMID- 16577625
TI  - Application of the Altmann Freezing-Drying Technique to Plant Cytology.

PMID- 16577627
TI  - Genetic Evolutionary Processes.

PMID- 16577626
TI  - Reversible Coagulation in Living Tissue: XII.

PMID- 16577628
TI  - Preferential Segregation of the Fourth Chromosomes in Drosophila melanogaster.

PMID- 16577629
TI  - On the Occurrence of an Oreodont Skeleton in the Sespe of South Mountain,
      California.

PMID- 16577630
TI  - On a Theorem of Carleman.

PMID- 16577631
TI  - Some Special Cases of the Indeterminacy Principle.

PMID- 16577632
TI  - Modified Ritz Method.

PMID- 16577633
TI  - A Discrimination without Previous Conditioning.

PMID- 16577634
TI  - Experiments on Early Developing Stages of Fundulus.

PMID- 16577635
TI  - The Rate and Extent of Anaerobic Decomposition of Sulfite Waste Liquor by
      Bacteria of Sea Water Mud.

PMID- 16577636
TI  - Note on the Location of the Critical Points of Harmonic Functions.

PMID- 16577638
TI  - Does "Protective Coloration" Protect?-Results of Some Experiments with Fishes and
      Birds.

PMID- 16577637
TI  - Correlation in Planarian Regeneration.

PMID- 16577639
TI  - The Accuracy of Least Squares.

PMID- 16577640
TI  - Ideals in Algebraic Rings.

PMID- 16577641
TI  - V(3) IN R(6) OF [1,2](a).

PMID- 16577642
TI  - The Fundamental Group of a Group Manifold.

PMID- 16577643
TI  - On the Foundations of a Constructive Theory of Discrete Commutative Algebra.

PMID- 16577644
TI  - Functionality in Combinatory Logic.

PMID- 16577645
TI  - The Calculation of Relative Multiplet Strengths in a Transition Array.

PMID- 16577646
TI  - The Localization of Pure Tones.

PMID- 16577647
TI  - Acetyl Choline and Chromatophores.

PMID- 16577649
TI  - A New Prehistoric Culture in Puerto Rico.

PMID- 16577648
TI  - On the Evolution of the Skulls of Vertebrates with Special Reference to Heritable
      Changes in Proportional Diameters (Anisomerism).

PMID- 16577650
TI  - The Individual Gene in Relation to the Chromomere and the Chromosome.

PMID- 16577651
TI  - Cricetine-Like Rodents from the Sespe Eocene of California.

PMID- 16577652
TI  - Fundamental Geodetic Surveys in the United States Nearing Completion.

PMID- 16577654
TI  - Groups Involving a Set of as Many Conjugates as Commutators.

PMID- 16577655
TI  - Sets of Group Elements Involving Only Products of More Than n.

PMID- 16577653
TI  - Time Measurements of an Ice Readvance at Littleton, N. H.

PMID- 16577656
TI  - The Temperature of the Copper Arc.

PMID- 16577657
TI  - Spheroidal Functions.

PMID- 16577658
TI  - Addition Formulae for Spheroidal Functions.

PMID- 16577659
TI  - On the Bending of Electromagnetic Micro-Waves Below the Horizon.

PMID- 16577660
TI  - The Snakes of the Genus Ninia.

PMID- 16577661
TI  - Rate of Growth and Length of Life.

PMID- 16577662
TI  - The Graptolites of the Simpson Group of Oklahoma.

PMID- 16577663
TI  - The Location of a Gene for Disease Resistance in Maize.

PMID- 16577664
TI  - Linkage Relations of Zavadskaia Shaker in the House Mouse (Mus musculus).

PMID- 16577665
TI  - Generation of any N-Valued Logic by One Binary Operation.

PMID- 16577666
TI  - Generalized Derivatives and Approximation.

PMID- 16577667
TI  - Abstract Critical Sets.

PMID- 16577668
TI  - On Convergence Factors for Series Summable by Norlund Means.

PMID- 16577669
TI  - Effective Equality and Effective Implication in Formal Logic.

PMID- 16577670
TI  - A Theorem on Extremals: I.

PMID- 16577671
TI  - A Proof of Freedom from Contradiction.

PMID- 16577672
TI  - Intensities of Vibration Rotation Bands.

PMID- 16577673
TI  - What Are the Resting and the Active States of Chromatophores?

PMID- 16577674
TI  - The Growth Hormone and the Dwarf Type of Growth in Corn.

PMID- 16577676
TI  - On the Chains of a Complex and Their Duals.

PMID- 16577675
TI  - The Dependence of Protection against a Transplantable Mouse Leukemia upon the
      Genetic Constitution of the Immunizing Tissue.

PMID- 16577677
TI  - On the Ring of a Compact Metric Space.

PMID- 16577678
TI  - On the Representation of Positive Harmonic Functions.

PMID- 16577679
TI  - Hunger-Contractions and Rate of Conditioning.

PMID- 16577680
TI  - The Assimilation of Ammonium Nitrogen by Nitzchia Closterium and Other Marine
      Phytoplankton.

PMID- 16577681
TI  - Groups in Which the Squares Generate a Subgroup of Index Less Than Seven.

PMID- 16577682
TI  - "Riemannian" Differential Geometry in Abstract Spaces.

PMID- 16577683
TI  - Asymptotic Representations of Confluent Hypergeometric Functions.

PMID- 16577684
TI  - Completely Integrable Differential Equations in Abstract Spaces.

PMID- 16577685
TI  - A Refinement of the Heisenberg Theory of Ferromagnetism, Applicable to Simple
      Cubic Crystals.

PMID- 16577686
TI  - Electrical Conductance of Short Gaps in Air.

PMID- 16577687
TI  - The Color Changes in Uca Pugilator.

PMID- 16577689
TI  - An Unbiased Correlation Ratio Measure.

PMID- 16577688
TI  - Processes of Localization in Developing Fundulus.

PMID- 16577690
TI  - A Determination of the Magnitude of the Cell "Sensitive Volume" Associated with
      the White-Eye Mutation in X-Rayed Drosophila.

PMID- 16577691
TI  - Further Data on Material Effects in Drosophila Pseudoobscura Hybrids.

PMID- 16577692
TI  - Occurrence of Lower Oligocene Mammal-Bearing Beds Near Death Valley, California.

PMID- 16577693
TI  - Adoption of the Meter-Kilogram-Mass-Second (M.K.S.) Absolute System of Practical
      Units by the International Electrotechnical Commission (I.E.C.), Bruxelles, June,
      1935.

PMID- 16577694
TI  - Preliminary Report on the Probable Connection between the Blood Gland and the
      Chromatophore Activator in Decapod Crustaceans.

PMID- 16577695
TI  - On the Bright Line Spectrum of Nova Herculis.

PMID- 16577696
TI  - Tissue Cultures of Spermatophytes.

PMID- 16577697
TI  - The Magnetic Properties and Structure of Hemoglobin, Oxyhemoglobin and
      Carbonmonoxyhemoglobin.

PMID- 16577698
TI  - Structure and Arrangement of Salivary Gland Chromosomes in Drosophila Species.

PMID- 16577700
TI  - The Metric Characterization of a Class of Spaces.

PMID- 16577699
TI  - Further Data on Linkage in Rabbits.

PMID- 16577701
TI  - On the Non-Vanishing of Certain Functions.

PMID- 16577702
TI  - The Evaluation of Ultra-Violet Solar Radiation of Short Wave-Lengths.

PMID- 16577703
TI  - The Double Innervation of Caudal Melanophores in Fundulus.

PMID- 16577704
TI  - Relations of Symmetry in the Developing Ear of Amblystoma Punctatum.

PMID- 16577705
TI  - A Second Law of the Motions of Eruptive Prominences.

PMID- 16577706
TI  - The Effect of Auxin on the Abscission of Petioles.

PMID- 16577707
TI  - Perissodactyla of the Sespe Eocene, California.

PMID- 16577709
TI  - The Effect of Temperature on the Respiration of the Earthworm.

PMID- 16577708
TI  - Extraterrestrial Effects of Cosmic Rays.

PMID- 16577710
TI  - The Change in the Response of Avena-Coleoptiles to Growth Regulations Produced by
      Aging.

PMID- 16577711
TI  - The Sexual and Reproductive Cycles of Chimpanzee.

PMID- 16577712
TI  - The Nearctic Dirhinini and Epitranini.

PMID- 16577713
TI  - Groups in Which the Squares of the Operators Generate a Cyclic Group.

PMID- 16577714
TI  - Mathematical Postulates for the Logical Operations of Assertion, Conjunction,
      Negation and Equality.

PMID- 16577715
TI  - Isometries of 2-Dimensional Riemannian Manifolds into Themselves.

PMID- 16577716
TI  - On the Connectivity Ring of a Bicompact Space.

PMID- 16577717
TI  - Conformal Geometry of Horn Angles.

PMID- 16577718
TI  - On Normal Coordinates.

PMID- 16577719
TI  - Functional Topology and Abstract Variational Theory.

PMID- 16577720
TI  - A Theory of Classes Presupposing no Canons of Type.

PMID- 16577721
TI  - On the Periodic Analytic Continuations of the Circular Orbits in the Restricted
      Problem of Three Bodies.

PMID- 16577722
TI  - On the Structure of Native, Denatured, and Coagulated Proteins.

PMID- 16577723
TI  - Inversions in the Third Chromosome of Wild Races of Drosophila Pseudoobscura, and
      Their Use in the Study of the History of the Species.

PMID- 16577724
TI  - The Effect of Temperature on the Frequency of Somatic Crossing-Over in Drosophila
      Melanogaster.

PMID- 16577725
TI  - Studies in Reptilian Color Change: I. A Preliminary Report.

PMID- 16577726
TI  - An Expansion-Luminosity Relation for Novae.

PMID- 16577727
TI  - Microincineration Studies: III. Shrinkage Phenomena during Carbonization and
      Ashing of Wood.

PMID- 16577728
TI  - Itidophycus Gen. Nov. and Its Representation in South America.

PMID- 16577729
TI  - Linkage Relations of Hydrocephalus (hy(1)) in the House Mouse, Mus Musculus.

PMID- 16577730
TI  - A Further Study of Regularity of Nutritional Response to Chemical Intake.

PMID- 16577731
TI  - The Elastic Properties of Rocks: A Correlation of Theory and Experiment.

PMID- 16577732
TI  - The Underlying Causes of Submarine Canyons.

PMID- 16577734
TI  - Photosynthesis in Relation to Light and Carbon Dioxide.

PMID- 16577733
TI  - On the Mechanism of Inhibition of Crayfish Muscle.

PMID- 16577735
TI  - On the Physiology of the Formation of Nodules on Legume Roots.

PMID- 16577736
TI  - The Nature of Tonal Brightness.

PMID- 16577738
TI  - Effects of Red Shifts on the Distribution of Nebulae.

PMID- 16577737
TI  - The Action of Intermedin on Crustacean Melanophores and of the Crustacean Hormone
      on Elasmobranch Melanophores.

PMID- 16577739
TI  - Inducement of Fruit Development by Growth-Promoting Chemicals.

PMID- 16577740
TI  - The Importance of Ash Elements in the Cultivation of Excised Root Tips.

PMID- 16577741
TI  - Growth Curve of Infants.

PMID- 16577742
TI  - The Mutation Rate in Somatic Cells of Maize.

PMID- 16577743
TI  - A Cytogenetic Demonstration of Crossing-Over Between X- and Y- Chromosomes in the
      Male Drosophila Melanogaster.

PMID- 16577744
TI  - Number of the Abelian Groups of a Given Order.

PMID- 16577745
TI  - Titanotheres from the Titus Canyon Formation, California.

PMID- 16577746
TI  - On the Saturation of Exchange Forces.

PMID- 16577747
TI  - The Triple Innervation of the Crayfish Muscle.

PMID- 16577748
TI  - On the Nature of Aural Harmonics.

PMID- 16577750
TI  - A Simplified Explanation of Bellamy's Experiments Concerning Sex Determination in
      Tropical Fishes.

PMID- 16577749
TI  - Plant Hormones and Mineral Nutrition.

PMID- 16577751
TI  - The Kinetic Basis of Crystal Polymorphism.

PMID- 16577752
TI  - The General Role of Composition in Polymorphism.

PMID- 16577754
TI  - On Some New Invariants of a Manifold.

PMID- 16577753
TI  - Notes on North American Leptodeira.

PMID- 16577755
TI  - Enumeration of the Abelian Groups Whose Orders Do Not Exceed a Given Number.

PMID- 16577756
TI  - Groups Whose Prime Powers Generate a Cyclic Subgroup.

PMID- 16577757
TI  - On Regular Rings.

PMID- 16577758
TI  - The Last Premeiotic Mitosis and Its Relation to Meiosis in Gaillardia.

PMID- 16577759
TI  - On the Integration of Operators.

PMID- 16577760
TI  - Groups Which Contain an Abelian Subgroup of Prime Index.

PMID- 16577761
TI  - Algebraic Theory of Continuous Geometries.

PMID- 16577762
TI  - On the Law for Minimal Discrimination of Intensities: I.

PMID- 16577763
TI  - On the Psychophysics of Hearing: I. Monaural Differential Sensitivity and
      Exposure Time.

PMID- 16577765
TI  - Stimulative and Inhibitive Induction in the Development of Primary and Secondary
      Sex Characters.

PMID- 16577764
TI  - On the Psychophysics of Hearing: II. Binaural Differential Sensitivity and
      Exposure-Time.

PMID- 16577766
TI  - An Evolutionary Analysis of Insular and Continental Species.

PMID- 16577767
TI  - On a New Cluster of Nebulae in Pisces.

PMID- 16577768
TI  - Electrokinetics: XIX. Interfacial Energy and the Molecular Structure of Organic
      Compounds. V. The Electric Moment of Al(2)O(3): Benzene-Nitrobenzene Interface.

PMID- 16577769
TI  - Application of a New Mathematical Method to Vibration-Rotation Interaction.

PMID- 16577770
TI  - The Effect of Radioactive Phosphorus upon the Blood of Growing Chicks.

PMID- 16577771
TI  - Effect of the Roots on the Production of Auxin by the Coleoptile.

PMID- 16577772
TI  - The Irreducible Representations of the Symmetric Group.

PMID- 16577774
TI  - On Products in a Complex.

PMID- 16577773
TI  - Groups of Order Less Than 2 Having m - 1 or m - 2 Independent Generators.

PMID- 16577775
TI  - Linear Orders.

PMID- 16577776
TI  - Hopf's Theorem for Non-Compact Spaces.

PMID- 16577777
TI  - Carotenoids and Other Lipoid-Soluble Pigments in the Sea and in Deep Marine Mud.

PMID- 16577778
TI  - Internuclear Distance in Oxygen Molecules.

PMID- 16577779
TI  - Bud Development in Lilium Harrisii Following Treatment with Indoleacetic Acid.

PMID- 16577780
TI  - The Distribution of Gene Frequencies in Populations.

PMID- 16577781
TI  - The Influence of Wave-Length on Genetic Effects of X-Rays.

PMID- 16577783
TI  - Groups Having a Maximum Number of Independent Generators.

PMID- 16577782
TI  - On the Theory of Beams Resting on a Yielding Foundation.

PMID- 16577784
TI  - Trihornometry: A New Chapter of Conformal Geometry.

PMID- 16577785
TI  - Continuous Rings and Their Arithmetics.

PMID- 16577786
TI  - Growth and Development of the Salivary Gland Chromosomes in Sciara.

PMID- 16577787
TI  - Development of Eye Colors in Drosophila: Relation between Pigmentation and
      Release of the Diffusible Substances.

PMID- 16577788
TI  - Autosomal Lethal Mutation Frequencies in Drosophila.

PMID- 16577789
TI  - Haploid Ovarian Tissue in Drosophila.

PMID- 16577790
TI  - Note on Transitive Transformations.

PMID- 16577791
TI  - Groups in Which Every Set of Independent Generators Is a Maximum Set.

PMID- 16577792
TI  - A Survey of Thirty-Six Thousand Southern Galaxies.

PMID- 16577793
TI  - The Growth of Plant Embryos in Vitro. Preliminary Experiments on the Role of
      Accessory Substances.

PMID- 16577794
TI  - The Eye-Stalk Hormone and Rate of Heart Beat in Crustaceans.

PMID- 16577795
TI  - The Seminal Vesicles of the Goby, with Preliminary Chemical and Physiological
      Studies of the Vesicular Fluid.

PMID- 16577796
TI  - The Inheritance of Sex at Endomixis in Paramecium Aurelia.

PMID- 16577797
TI  - A Third Lethal in the T (Brachy) Series in the House Mouse.

PMID- 16577798
TI  - An Accelerating Effect of Normal "Ring-Glands" on Puparium-Formation in Lethal
      Larvae of Drosophila Melanogaster.

PMID- 16577799
TI  - Frequency of Induced Breaks in Chromosomes of Drosophila Melanogaster.

PMID- 16577800
TI  - On the Direct Product of Irreducible Representations of the Symmetric Group.

PMID- 16577801
TI  - Degree of Approximation by Polynomials-Problem alpha.

PMID- 16577802
TI  - Sets of Independent Generators of a Finite Group.

PMID- 16577803
TI  - On Functional Equations in Linear Topological Spaces.

PMID- 16577804
TI  - Intermediates of Vitamin B(1) and Growth of Phycomyces.

PMID- 16577805
TI  - Mechanism of Symbiotic Nitrogen Fixation: II. The pO(2) Function.

PMID- 16577806
TI  - On the Law for Minimal Discrimination of Intensities: II.

PMID- 16577807
TI  - Specific Constants for Visual Excitation.

PMID- 16577808
TI  - The Rates of Absorption of Radio-Sodium in Normal Human Subjects.

PMID- 16577809
TI  - The Deposition of Radio Phosphorus in Tissues of Growing Chicks.

PMID- 16577810
TI  - The Occurrence of a Dominant Spotting Mutation in the House Mouse.

PMID- 16577811
TI  - Succession of Fossil Floras in Patagonia.

PMID- 16577812
TI  - Skin Transplants between Embryos of Different Breeds of Fowl.

PMID- 16577813
TI  - General Projective Differential Geometry.

PMID- 16577815
TI  - On the Concept of Co-Sets in a Semi-Group.

PMID- 16577814
TI  - Groups in Which Every Subgroup of Composite Order Is Invariant.

PMID- 16577816
TI  - On Generations of the Numbers of Bernoulli and Euler.

PMID- 16577817
TI  - Some North Pacific Species of Articulated Corallines.

PMID- 16577819
TI  - The Stability of the Radiative Gradients in the Interior of a Star.

PMID- 16577818
TI  - New Species of Arctiulated Corallines from South Africa.

PMID- 16577820
TI  - Plant Parts of Deciduous Fruits Which Give Evidence of Being Favorable for Tissue
      Culture.

PMID- 16577821
TI  - Transfinite Real Numbers.

PMID- 16577822
TI  - Groups Which Contain a Hamiltonian Subgroup of Odd Prime Index.

PMID- 16577823
TI  - Differential Invariants in a General Differential Geometry.

PMID- 16577824
TI  - Antidromic Responses from the Melanophore Nerves of the Catfish Ameiurus.

PMID- 16577825
TI  - Antagonism in Neurohumors as Seen in the Pectoral Bands of Mustelus.

PMID- 16577826
TI  - The Four Transverse Magnetic Effects in Copper: New Measurements.

PMID- 16577827
TI  - On the Magnetic Theory of Supraconductors.

PMID- 16577828
TI  - Acid Catalysis in Liquid Ammonia. Ammonolysis of Diethylmalonate.

PMID- 16577829
TI  - The Structure of Cyameluric Acid, Hydromelonic Acid and Related Substances.

PMID- 16577830
TI  - Spontaneous Chromatin Rearrangements and the Theory of the Gene.

PMID- 16577831
TI  - Regulation of Heat Loss from the Human Body.

PMID- 16577832
TI  - The Physical Laws of Heat Loss from the Human Body.

PMID- 16577833
TI  - Relative Numbers of Operators and Subgroups of a Finite Group.

PMID- 16577834
TI  - Minimum Degree of Substitutions of Highest Degree in a Group.

PMID- 16577835
TI  - Measurements of Resistance and Capacity of Monofilms of Barium Stearate.

PMID- 16577837
TI  - Note on Estimating Bacterial Populations by the Dilution Method.

PMID- 16577836
TI  - Translocation in Relation to Mosaic Formation in Maize.

PMID- 16577838
TI  - Temperature and the Critical Intensity for Response to Visual Flicker.

PMID- 16577839
TI  - Specific Constants for Visual Excitation: II.

PMID- 16577840
TI  - The Relations Between Stefan's Radiation Law, Nernst's Heat Theorem and Maxwell's
      Formula for the Radiation Pressure.

PMID- 16577841
TI  - The Distribution of Gene Frequencies Under Irreversible Mutation.

PMID- 16577842
TI  - Auxin in Isolated Roots Growing in Vitro.

PMID- 16577843
TI  - The Mechanism of Hearing as Revealed Through Experiment on the Masking Effect of
      Thermal Noise.

PMID- 16577844
TI  - The Dimensionless Constants of Physics.

PMID- 16577845
TI  - On the Relative Contributions of Nature and Nurture to Average Group Differences
      in Intelligence.

PMID- 16577846
TI  - A Metagalactic Density Gradient.

PMID- 16577847
TI  - A Tarsiid Primate and a Mixodectid from the Poway Eocene, California.

PMID- 16577848
TI  - Largest Degree of a Substitution in the Groups of a Given Degree.

PMID- 16577849
TI  - Remarks on Riemann's Doctoral Dissertation.

PMID- 16577850
TI  - Some Recent Observations of Sunspot Spectra.

PMID- 16577851
TI  - Second Note on a Metagalactic Density Gradient.

PMID- 16577852
TI  - Reflectivity and Color of Meteorites.

PMID- 16577853
TI  - On the Duplexity Theory of Visual Response in Vertebrates: II.

PMID- 16577854
TI  - Specific Constants for Visual Excitation: III.

PMID- 16577855
TI  - The Effects of Chemicals on the Lethal Mutation Rate in Drosophila Melanogaster.

PMID- 16577856
TI  - An Internal Secretion Affecting Viability in Crustacea.

PMID- 16577857
TI  - The Consistency of the Axiom of Choice and of the Generalized Continuum
      Hypothesis.

PMID- 16577858
TI  - The Characterization of Pseudo-S Sets.

PMID- 16577859
TI  - On Semi-Groups of Selfadjoint Transformations in Hilbert Space.

PMID- 16577860
TI  - Groups of Order p Containing m - alpha Independent Generators.

PMID- 16577861
TI  - Vitamin B(6), a Growth Substance for Excised Tomato Roots.

PMID- 16577862
TI  - The Induction by Irradiation with Neutrons of Hereditary Changes in Mice.

PMID- 16577863
TI  - Imaginal Differentiation Inaugurated by Oxygen in Drosophila Pupae.

PMID- 16577864
TI  - Experiments on the Relation of Nutrition to the Composition of the Body and the
      Length of Life.

PMID- 16577866
TI  - The Steady Polarity Potential of the Human Eye.

PMID- 16577865
TI  - The Resolution of Tests into Two General Factors.

PMID- 16577867
TI  - Chemical Restoration in Nitella: III. Effects of Inorganic Salts.

PMID- 16577868
TI  - The Physical State of the Interstellar Gas Clouds.

PMID- 16577869
TI  - Groups of Degree n in Which the Largest Degree of a Substitution is a Minimum.

PMID- 16577870
TI  - Euler's Concordant Forms.

PMID- 16577871
TI  - On the Mapping of Abstract Spaces on Polytopes.

PMID- 16577872
TI  - The Intrinsic Metric of a Polytope.

PMID- 16577873
TI  - On the Concept of a Topological Space.

PMID- 16577874
TI  - Photomicrographs of Thin Bone Sections by the Use of Fluorescence X-Radiation.

PMID- 16577875
TI  - A Determination of the Distance to the Galactic Center.

PMID- 16577876
TI  - Supernovae and Stellar Collisions.

PMID- 16577877
TI  - Observations on Chromosome Elimination in the Germ Cells of Sciara Ocellaris.

PMID- 16577878
TI  - Reliability of Measurements of the Steady Polarity Potential of the Eye.

PMID- 16577879
TI  - On the Subdivision of the Genus Drosophila.

PMID- 16577880
TI  - Embryo-Sac Development in Plumbagella.

PMID- 16577881
TI  - The Distribution of Intermedin in the Pars Anterior of the Chicken Pituitary.

PMID- 16577882
TI  - The Convex Cells Formed by Seven Planes.

PMID- 16577883
TI  - On the Existence of Minimal Surfaces of General Critical Types.

PMID- 16577884
TI  - Additive Set Functions on Groups.

PMID- 16577885
TI  - The Time Factor in X-Ray Production of Chromosome Aberrations.

PMID- 16577886
TI  - Induction of Triploidy and Haploidy in the Newt, Triturus Viridescens, by Cold
      Treatment of Unsegmented Eggs.

PMID- 16577888
TI  - Influences of Limiting Magnitude upon Meteor Frequency.

PMID- 16577887
TI  - The Role of Developmental Rates in the Production of Notched Wing Characters in
      Drosophila Melanogaster.

PMID- 16577889
TI  - Is Auxin Produced in Roots?

PMID- 16577890
TI  - Cell Polarity and the Differentiation of Root Hairs.

PMID- 16577891
TI  - On modular and p-adic representations of algebras.

PMID- 16577893
TI  - The Transformation of a Lagrangian Series into a Newtonian Series.

PMID- 16577892
TI  - Number of the Subgroups of Any Abelian Group.

PMID- 16577894
TI  - The Constitution of Secretin.

PMID- 16577895
TI  - Eocene Amynodonts from Southern California.

PMID- 16577896
TI  - The Active Uptake of Ions into Cells and Organisms.

PMID- 16577897
TI  - Mammary Tumor Development in Mice Ovariectomized at Birth.

PMID- 16577898
TI  - Observations on the Mechanism of Induced Chromosome Rearrangements in Sciara.

PMID- 16577900
TI  - Class Field Theory of Solvable Algebraic Number Fields.

PMID- 16577899
TI  - Evidence for the Existence of an Electro-Dynamic Field in Living Organisms.

PMID- 16577901
TI  - On the Representation of Groups of Finite Order.

PMID- 16577902
TI  - Ordered Sets, Complexes and the Problem of Compactification.

PMID- 16577903
TI  - Preliminary Notes on the Development of the Wings in Normal and Mutant Strains of
      Drosophila.

PMID- 16577904
TI  - High Mutation Frequency Induced by Hybridization.

PMID- 16577906
TI  - A Remarkable Group of Position-Effects.

PMID- 16577905
TI  - Microgeographic Variation in Drosophila Pseudoobscura.

PMID- 16577907
TI  - Extraction of an Egg-Membrane-Lysin from Sperm of the Giant Keyhole Limpet
      (Megathura Crenulata).

PMID- 16577908
TI  - The Wound Hormones of Plants: II. The Isolation of a Crystalline Active
      Substance.

PMID- 16577909
TI  - The Chemical Induction of Genetic Changes in Fungi.

PMID- 16577910
TI  - Polysomaty in Cucumis Melo.

PMID- 16577911
TI  - Production of Atomic Rays and of Cosmic Rays in Supernovae.

PMID- 16577912
TI  - An Experiment in Human Vitamin A-Deficiency.

PMID- 16577914
TI  - Team Tests for Generals and Specifics.

PMID- 16577913
TI  - The Steady Potential of the Human Eye in Subjects with Unilateral Enucleation.

PMID- 16577915
TI  - Independent Generators of the Subgroups of an Abelian Group.

PMID- 16577916
TI  - Groups Having a Small Number of Subgroups.

PMID- 16577918
TI  - The Analytic Prolongation of a Minimal Surface across a Straight Line.

PMID- 16577917
TI  - On Chain-Mappings Carried by Cell-Mappings.

PMID- 16577919
TI  - The Automatic Synthesis of Speech.

PMID- 16577921
TI  - The Aerodynamics of Reacting Substances.

PMID- 16577920
TI  - The Photography of Interatomic Distance Vectors and of Crystal Patterns.

PMID- 16577922
TI  - A Question in General Relativity.

PMID- 16577923
TI  - The Effect of Temperature on X-Ray Induced Chromosome Aberrations.

PMID- 16577924
TI  - The Behavior in Successive Nuclear Divisions of a Chromosome Broken at Meiosis.

PMID- 16577925
TI  - The Influence of Transplantation upon Immunological Properties of Leukemic Cells.

PMID- 16577926
TI  - Responses to Different Levels of Nutritional Intake of Riboflavin (Formerly
      Called Vitamin G).

PMID- 16577928
TI  - Critical Points of a Map to a Circle.

PMID- 16577927
TI  - Galactic and Extragalactic Studies: I. On the Corona of Stars Around the Galactic
      System.

PMID- 16577929
TI  - Groups Containing a Prime Number of Non-Invariant Subgroups.

PMID- 16577930
TI  - Identification of Two Subsets.

PMID- 16577931
TI  - The Weak Topologies of Banach Spaces.

PMID- 16577932
TI  - Abstract Flat Projective Geometry.

PMID- 16577933
TI  - Developmental Changes in Apical Meristems.

PMID- 16577934
TI  - The Synthesis of Sulfonyl Chlorides by Chlorination of Sulphur Compounds.

PMID- 16577935
TI  - Hybridization and Tumor Formation in Mice.

PMID- 16577936
TI  - Nuclease Action, Protease Action and Histochemical Tests on Salivary Chromosomes
      of Drosophila.

PMID- 16577937
TI  - Adjusted Death Rates.

PMID- 16577938
TI  - The Gravitational Motion of a Pair of Rigid Bodies.

PMID- 16577939
TI  - A Theory of Length and Its Applications to the Calculus of Variations.

PMID- 16577940
TI  - General Trihornometry of Second Order.

PMID- 16577941
TI  - Groups Which Contain Less Than Ten Proper Subgroups.

PMID- 16577942
TI  - Development of Eye-Colors in Drosophila: Bacterial Synthesis of v Hormone.

PMID- 16577945
TI  - The Breeding of Some Rabbits Produced by Recipients of Artificially Activated
      Ova.

PMID- 16577944
TI  - A Study of Feather Character in Limbs Transplanted between Embryos of Different
      Bird Species.

PMID- 16577943
TI  - Nutritional Requirements of Drosophila Melanogaster.

PMID- 16577946
TI  - On Periodicities in Measures of the Solar Constant.

PMID- 16577947
TI  - Galactic and Extragalactic Studies: II. Notes on the Peculiar Stellar Systems in
      Sculptor and Fornax.

PMID- 16577948
TI  - Three Supernovae in the Spiral NGC 3184.

PMID- 16577949
TI  - Distribution of Induced Breaks along the X-Chromosome of Drosophila Melanogaster.

PMID- 16577950
TI  - A Theory of the Color of Dyes.

PMID- 16577951
TI  - Prime Power Groups Determined by the Number of Their Subgroups.

PMID- 16577952
TI  - On Basis Systems for Groups of Ideal Classes in a Properly Irregular Cyclotomic
      Field.

PMID- 16577953
TI  - Analysis of Variance Applied to Human Genetics.

PMID- 16577954
TI  - "Personality" Differences as Described by Invariant Properties of Individuals in
      Interaction.

PMID- 16577956
TI  - Concerning the Open Subsets of a Plane Continuum.

PMID- 16577955
TI  - The Nature of Absorption of Radioactive Isotopes by Living Tissues as Illustrated
      by Experiments with Barley Plants.

PMID- 16577957
TI  - On Homotopy and Extension of Mappings.

PMID- 16577958
TI  - Integration and Differentiation in Partially Ordered Spaces.

PMID- 16577959
TI  - Two X-Ray Induced Mosaics in Drosophila Pseudoobscura.

PMID- 16577961
TI  - On the Determination of the Orbital Elements of Eccentric Eclipsing Binaries.

PMID- 16577960
TI  - Galactic and Extragalactic Studies: III. Photographs of Thirty Southern Nebulae
      and Clusters.

PMID- 16577962
TI  - Galactic and Extragalactic Studies: IV. Photometry of Two Large Southern Clusters
      of Galaxies.

PMID- 16577963
TI  - The Doppler Effect in Resonance Lines.

PMID- 16577964
TI  - The Theory of the Visual Threshold: I. Time and Intensity.

PMID- 16577965
TI  - Temperature and the Critical Intensity for Response to Visual Flicker: IV. On the
      Invariance of Critical Thermal Increments, and the Theory of the Response
      Contour.

PMID- 16577966
TI  - On Spinal Shock.

PMID- 16577967
TI  - Physiology of Development of the Feather: IV. The Diurnal Curve of Growth in
      Brown Leghorn Fowl.

PMID- 16577968
TI  - The Size of the Tobacco Mosaic Particle from X-Ray Determinations.

PMID- 16577969
TI  - The Pigment-Forming Potency of Early Chick Blastoderms.

PMID- 16577970
TI  - Simultaneous Measures of Human Relations and Emotional Activity.

PMID- 16577971
TI  - Galactic and Extragalactic Studies: VII. Magnitudes of Forty Cepheids in the
      Large Magellanic Cloud.

PMID- 16577973
TI  - The Theory of the Visual Threshold: II. On the Kinetics of Adaptation.

PMID- 16577972
TI  - Further Remarks on the Cosmological Time Scale.

PMID- 16577974
TI  - Effects of Certain Chemical Treatments on the Morphology of Salivary Gland
      Chromosomes and Their Interpretation.

PMID- 16577975
TI  - Abelian Groups Which Contain No More Than 25 Proper Subgroups.

PMID- 16577976
TI  - On the Intersections of Irreducible Components in the Manifold of a Differential
      Polynomial.

PMID- 16577977
TI  - Differentials of Functions with Arguments and Values in Topological Abelian
      Groups.

PMID- 16577978
TI  - Triangulated Manifolds Which Are Not Brouwer Manifolds.

PMID- 16577979
TI  - Some in vivo Effects of Localized Nuclear Disintegration Products on a
      Transplantable Mouse Sarcoma.

PMID- 16577980
TI  - Galactic and Extragalactic Studies: X. Note on Latitude Effect and Radial
      Gradients in the Northern Galactic Hemisphere.

PMID- 16577981
TI  - The Effect of Shear Instability on the Transverse Circulation in the Atmosphere.

PMID- 16577983
TI  - On an Inequality of Grunsky.

PMID- 16577982
TI  - On the Mortality in Husbands and Wives.

PMID- 16577984
TI  - Minimal Cross-Cut Subgroups Relative to the Product of Their Orders.

PMID- 16577985
TI  - The Influence of Nerve Fibers upon Taste Buds During Embryonic Development.

PMID- 16577986
TI  - Touch-and-Go Pairing in Chromosomes.

PMID- 16577987
TI  - The Correction of X-Ray Diffraction Intensities for Lorentz and Polarization
      Factors.

PMID- 16577988
TI  - Fucus Cordatus Turner.

PMID- 16577989
TI  - Every Two Equal Order Subgroups Having Only Identity in Common.

PMID- 16577990
TI  - Generalized Homology Groups.

PMID- 16577991
TI  - Functions Whose Even Derivatives Have a Prescribed Sign.

PMID- 16577992
TI  - On Green's Formula.

PMID- 16577993
TI  - Surfaces of Minimum Capacity.

PMID- 16577994
TI  - Boundary Values of Functions Satisfying a Linear Partial Differential Equation of
      Elliptic Type.

PMID- 16577995
TI  - Notes on Binary Stars: III. The Ellipticity Effect in Eccentric Eclipsing
      Binaries.

PMID- 16577996
TI  - Bivalent Structure in the Fly, Melophagus Ovinus L. (Pupipara, Hippoboscidae).

PMID- 16577997
TI  - Some Effects of the Gene W(Dominant Spotting) in Mice.

PMID- 16577998
TI  - Optically Reciprocal Gratings and Their Application to Synthesis of Fourier
      Series.

PMID- 16577999
TI  - Serological Reactions with Simple Substances Containing Two or More Haptenic
      Groups.

PMID- 16578000
TI  - Progressive Immunization.

PMID- 16578001
TI  - On Dirichlet's Divisor Plan.

PMID- 16578003
TI  - Notes on Binary Stars: I. On the Surface Gravity of a Rotationally and Tidally
      Distorted Star.

PMID- 16578002
TI  - Uniqueness Theorems for Conformal Mapping of Multiply Connected Domains.

PMID- 16578004
TI  - Notes on Binary Stars: II. On the Light of Eclipsing Binaries Out of Eclipse.

PMID- 16578005
TI  - Vitamin B Requirements of Drosophila Melanogaster.

PMID- 16578006
TI  - The Electric Stimulation of the Concentrating (Adrenergic) and the Dispersing
      (Cholinergic) Nerve-Fibres of the Melanophores in the Catfish.

PMID- 16578007
TI  - X-Ray Induced Chromosome Rearrangements in the Females of Sciara.

PMID- 16578008
TI  - The Infra-Red Spectra of SiH(4) and GeH(4).

PMID- 16578009
TI  - Maximal Subgroups of a Finite Group.

PMID- 16578010
TI  - On Functions Whose Derivatives Do Not Vanish in a Given Interval.

PMID- 16578011
TI  - Note on a Canonical Form for the Linear q-Difference System.

PMID- 16578012
TI  - On the Stability of the Linear Functional Equation.

PMID- 16578013
TI  - Pigments from Marine Muds.

PMID- 16578014
TI  - Female Sterility in Interracial Hybrids of Drosophila Pseudoobscura.

PMID- 16578015
TI  - Groups Containing Maximal Subgroups of Prime Order.

PMID- 16578016
TI  - On the Riemann Hypothesis in Function-Fields.

PMID- 16578017
TI  - The Group Ring of a Locally Compact Group: I.

PMID- 16578018
TI  - Conditional Invariants.

PMID- 16578019
TI  - The Dirac Equation and Conditional Invariants.

PMID- 16578020
TI  - The Pyridine Analog of Thiamin and the Growth of Fungi.

PMID- 16578021
TI  - Thiazole Effect on Phycomyces.

PMID- 16578022
TI  - The Probable Explanation of Low Transmission Ratios of Certain Monosomic Types of
      Nicotiana Tabacum.

PMID- 16578023
TI  - Natural and Induced Changes in Chromosome Structure in Maize Endosperm.

PMID- 16578024
TI  - Antithetical Dominance in North American Maize.

PMID- 16578025
TI  - Galactic and Extragalactic Studies: XII. The Giant Globular Cluster 47 Tucanae
      and Its Long-Period Variables.

PMID- 16578026
TI  - Groups Containing a Maximal Proper Subgroup of Order 4.

PMID- 16578027
TI  - Topology Based upon the Concept of a Pseudo-Norm.

PMID- 16578029
TI  - Unstable Minimal Surfaces with Any Rectifiable Boundary.

PMID- 16578028
TI  - Concerning the Differential Equations of Some Boundary Layer Problems: II.

PMID- 16578030
TI  - On Homogeneous Measure Algebras.

PMID- 16578031
TI  - On the Depolarization of Neutron Beams by Magnetic Fields.

PMID- 16578032
TI  - Hypoxanthine, a Growth Substance for Phycomyces.

PMID- 16578034
TI  - The Oxidation of 3,5-Diiodotyrosine to Thyroxine.

PMID- 16578033
TI  - Size Genes of Mice.

PMID- 16578035
TI  - Complement Fixation with Simple Substances Containing Two or More Haptenic
      Groups.

PMID- 16578036
TI  - Maximal Sylow Subgroups of a Given Group.

PMID- 16578037
TI  - An Inverse Problem Concerning a Chain Process.

PMID- 16578038
TI  - On Confidence Intervals.

PMID- 16578039
TI  - On Contingency Tables.

PMID- 16578041
TI  - The Distribution of X-Ray Induced Chromosomal Aberrations.

PMID- 16578040
TI  - The Release of Auxin from Isolated Leaf Proteins of Spinach by Enzymes.

PMID- 16578043
TI  - The Dissociation Constant in Nitrogen Fixation by Azotobacter.

PMID- 16578042
TI  - Genetic Control of Biochemical Reactions in Neurospora: An "Aminobenzoicless"
      Mutant.

PMID- 16578044
TI  - Some Deductions from Frobenius's Theorem.

PMID- 16578045
TI  - On Monothetic Groups.

PMID- 16578046
TI  - On the Dirichlet Problem for the Hyperbolic Case.

PMID- 16578047
TI  - Chromosomes of the Red Fox.

PMID- 16578048
TI  - Salivary Gland Type Chromosomes in Mosquitoes.

PMID- 16578049
TI  - Purines as Growth Requirements of Spirillum Serpens.

PMID- 16578050
TI  - The Distribution of Metallic Atoms in Two-Component Glasses.

PMID- 16578051
TI  - A New Fourier Series Technique for Crystal Structure Determination.

PMID- 16578052
TI  - Synthesis of Vitamins by Intestinal Bacteria.

PMID- 16578053
TI  - Theory of the Effects of Light Intensity and Duration in Determining Visual
      Responses.

PMID- 16578054
TI  - Stationary Points of Transformation Groups.

PMID- 16578055
TI  - Note on the t-Test.

PMID- 16578056
TI  - Some Factors Affecting the Toxicity of Cultures of Shigella Dysenteriae.

PMID- 16578057
TI  - The Fusion of Broken Ends of Chromosomes Following Nuclear Fusion.

PMID- 16578058
TI  - Non-Random Uncoiling in Heterobrachial Chromosomes.

PMID- 16578059
TI  - Tumor Formation by Attenuated Crown-Gall Bacteria in the Presence of Growth
      Promoting Substances.

PMID- 16578061
TI  - On the Material Ejected from Novae.

PMID- 16578060
TI  - The Role of Intracellular Cations on Liver Glycogen Formation in Vitro.

PMID- 16578062
TI  - On the Dimensions and Constitution of Variable Stars.

PMID- 16578063
TI  - A Study of the RV Tauri Variables.

PMID- 16578064
TI  - Galactic and Extragalactic Studies: XVI. Photographic Amplitudes of Classical
      Cepheids.

PMID- 16578066
TI  - Synthesis of Riboflavin by a Yeast.

PMID- 16578065
TI  - Electrical Correlates of Pure and Hybrid Strains of Sweet Corn.

PMID- 16578067
TI  - Pseudopyridoxine and Certain Fungi.

PMID- 16578068
TI  - The Distribution of Phosphatase in the Spinal Cord of Chick Embryos of One to
      Eight Days' Incubation.

PMID- 16578069
TI  - Studies on the Methane Fermentation: VI. The Influence of Carbon Dioxide
      Concentration on the Rate of Carbon Dioxide Reduction by Molecular Hydrogen.

PMID- 16578070
TI  - Effect of Colchicine Pretreatment on the Frequency of Chromosomal Aberrations
      Induced by X-Radiation.

PMID- 16578071
TI  - Some Topologically Invariant Metric Properties.

PMID- 16578072
TI  - On a Statistical Generalization of Metric Spaces.

PMID- 16578073
TI  - A Sufficient Condition That a C-Characteristic Be Geometric.

PMID- 16578074
TI  - Further Observations on the Specificity of Hypoxanthine for Phycomyces.

PMID- 16578075
TI  - A Mutant of Drosophila Melanogaster Resembling the So-Called Unstable Genes of
      Drosophila Virilis.

PMID- 16578076
TI  - A Table Determining L.D.50 or the Fifty Per Cent End-Point.

PMID- 16578077
TI  - Groups Containing Four and Only Four Non-Invariant Subgroups.

PMID- 16578078
TI  - On Infinite Dimensional Linear Spaces.

PMID- 16578079
TI  - On Certain Non-Linear Differential Equations of the Second Order.

PMID- 16578080
TI  - The Structure and Function of the Golgi System in the Living Cells of Developing
      Molluscs.

PMID- 16578081
TI  - The Relation between the Golgi Apparatus and "Droplets" in the Cell Stainable
      Vitally with Methylene Blue.

PMID- 16578082
TI  - Matter, Electricity and Gravitation in Flat Space-Time.

PMID- 16578083
TI  - Groups of Transformations of the Non-Invariant Subgroups.

PMID- 16578084
TI  - On the Uniform Convergence of the Solutions of the Navier-Stokes Equations.

PMID- 16578085
TI  - Relationship between Particle Size and Efficiency of Palladium-Polyvinyl
      Alcohol(Pd-PVA) Catalysts.

PMID- 16578087
TI  - Dynamical Trajectories in a Resisting Medium.

PMID- 16578086
TI  - The Determination of L.D.50 and Its Sampling Error in Bio-Assay: III.

PMID- 16578088
TI  - Dynamical Trajectories of the Curvature Type.

PMID- 16578089
TI  - Union-Preserving Transformations of Differential-Elements.

PMID- 16578090
TI  - A Formula for the Stream Function of Certain Flows.

PMID- 16578091
TI  - Strain Specificity and Production of Antibiotic Substances: II. Aspergillus
      Flavus-Oryzae Group.

PMID- 16578092
TI  - Competition between Free and Combined Nitrogen in Nutrition of Azotobacter.

PMID- 16578094
TI  - New Characterizations of Segments and Arcs.

PMID- 16578093
TI  - Groups Containing a Prime Number of Conjugate Subgroups.

PMID- 16578095
TI  - Some Preliminary Studies on the Mechanism of Virus Multiplication.

PMID- 16578096
TI  - The Determination of L.D.50 and Its Sampling Error in Bio-Assay: II.

PMID- 16578097
TI  - Concerning the Relation between Structure and Action of Xanthones on
      Dehydrogenations by Fusaria.

PMID- 16578098
TI  - Goniolithon and Neogoniolithon: Two Genera of Crustaceous Coralline Algae.

PMID- 16578099
TI  - New or Little Known Crustaceous Corallines of Pacific North America.

PMID- 16578100
TI  - Linear Partial Differential Equations with Analytic Coefficients.

PMID- 16578101
TI  - A Pericentric Inversion in Gasteria Resulting in Apparent Iso-Chromosomes at
      Meiosis.

PMID- 16578102
TI  - Mechanism of Enzymatic Adaptation in Genetically Controlled Yeast Populations.

PMID- 16578103
TI  - Studies on the Development of the Eye: Evidence that the Lobe, Lobe, Lobe and
      Eyeless Mutants of Drosophila Melanogaster Develop in a Manner Similar to Bar.

PMID- 16578104
TI  - Relative Number of Non-Invariant Operators in a Group.

PMID- 16578105
TI  - Note on the Function F(a, b; c - n; z).

PMID- 16578106
TI  - Indole and Serine in the Biosynthesis and Breakdown of Tryptophane.

PMID- 16578108
TI  - Respiratory Rates of the Shoot Tips and Maturing Tissues in Lupinus Albus and
      Tropaeolum Majus.

PMID- 16578107
TI  - A Second Approximation to Soper's Epidemic Curve.

PMID- 16578109
TI  - Invalidation of the Cytological Evidence for Reciprocal Chiasmata in the Sex
      Chromosome Bivalent of Male Drosophila.

PMID- 16578110
TI  - Birkhoff's Theory of Gravitation and Einstein's Theory for Weak Fields.

PMID- 16578111
TI  - On the Theory of Characters of Groups and Semi-Groups in Normed Vector Rings.

PMID- 16578112
TI  - Galactic and Extragalactic Studies: XVII. Revision of the Distances of Thirty
      High-Latitude Globular Clusters.

PMID- 16578114
TI  - Linkage Studies of the Rat (Rattus Norvegicus): VI.

PMID- 16578113
TI  - The Behavior of Oppositional Alleles in Polyploids of Trifolium Repens.

PMID- 16578115
TI  - Equilibrium in Genic Materials.

PMID- 16578116
TI  - On the Role of Carbon Dioxide in the Metabolism of Clostridium Thermoaceticum.

PMID- 16578117
TI  - The Matrices of Factor Analysis.

PMID- 16578118
TI  - Laplace Transforms of a Class of Higher Dimensional Varieties in a Projective
      Space of n Dimensions.

PMID- 16578120
TI  - On the Arithmetic in a Group Ring.

PMID- 16578119
TI  - Permutable Periodic Transformations.

PMID- 16578121
TI  - Possible Numbers of Non-Invariant Operators of a Group.

PMID- 16578122
TI  - The Biological Effects of X-Rays as a Function of Intensity.

PMID- 16578124
TI  - X-Ray Sensitivity Changes in Meiotic Chromosomes.

PMID- 16578123
TI  - Strain Specificity and Production of Antibiotic Substances: III. Penicillium
      Notatum-Chrysogenum Group.

PMID- 16578125
TI  - The Spore Discharge Mechanism of Common Ferns.

PMID- 16578127
TI  - The Span of the Translations of a Function in a Lebesgue Space.

PMID- 16578128
TI  - On the Solution of a General Transform.

PMID- 16578126
TI  - Scale Curves in Conformal Maps.

PMID- 16578129
TI  - Vision and Guanine Production in Fishes.

PMID- 16578130
TI  - The Identification of Guanine in Extracts of Girella Nigricans: The Specificity
      of Guanase.

PMID- 16578131
TI  - On Spontaneous Mutation.

PMID- 16578132
TI  - One-Band Inversion.

PMID- 16578133
TI  - Chromosome Associations in Tetraploid Hybrids between Prime Type 1 and Prime Type
      2 in Datura Stramonium.

PMID- 16578134
TI  - On Mechanical Self-Excited Oscillations.

PMID- 16578135
TI  - First Proof that the Mersenne Number M(157) Is Composite.

PMID- 16578136
TI  - On the Stability of Two-Dimensional Parallel Flows.

PMID- 16578137
TI  - Flat Space-Time and Gravitation.

PMID- 16578138
TI  - On Surface Area.

PMID- 16578139
TI  - On the Genetic Control of Mutability in Maize.

PMID- 16578140
TI  - Maintenance and Increase of a Genetic Character by a Substrate-Cytoplasmic
      Interaction in the Absence of the Specific Gene.

PMID- 16578141
TI  - Vitamin A in Relation to Aging and to Length of life.

PMID- 16578143
TI  - Axiomatic Approach to Homology Theory.

PMID- 16578142
TI  - The Law of Mass Action in Epidemiology: II.

PMID- 16578144
TI  - Awards to the Academy and Research Council.

PMID- 16578145
TI  - Irregular Projective Invariants.

PMID- 16578146
TI  - Euler's Three Biquadrate Problem.

PMID- 16578147
TI  - Strain Specificity and Production of Antibiotic Substances: IV. Variations Among
      Actionomycetes, with Special Reference to Actinomyces Griseus.

PMID- 16578148
TI  - On Epinephrine and Retinal Photomechanical Responses.

PMID- 16578149
TI  - The Variation of Infectivity.

PMID- 16578151
TI  - The Velocity of Propagation of Brittle Cracks in Steel.

PMID- 16578150
TI  - Groups Having a Small Number of Sets of Conjugate Subgroups.

PMID- 16578152
TI  - On the Evolution of Biochemical Syntheses.

PMID- 16578153
TI  - Strain Specificity and Production of Antibiotic Substances: V. Strain Resistance
      of Bacteria to Antibiotic Substances, Especially to Streptomycin.

PMID- 16578154
TI  - Stabilizing Influence of Liberal Intake of Vitamin A.

PMID- 16578155
TI  - Illustrations and Simple Abstract Proof of Sylow's Theorem.

PMID- 16578157
TI  - A Contribution to the Cytology of the Australian-South Pacific Species of
      Nicotiana.

PMID- 16578156
TI  - On the Number of Solutions of Certain Non-Homogeneous Trinomial Equations in a
      Finite Field.

PMID- 16578158
TI  - On a Class of Hermitian Transformations Containing Self-Adjoint Differential
      Operators.

PMID- 16578159
TI  - New Types of Relations in Finite Field Theory (Second Paper).

PMID- 16578160
TI  - On Algebraic Lie Algebras.

PMID- 16578161
TI  - Two Integral Equations.

PMID- 16578162
TI  - Vital Statistics of the National Academy of Sciences.

PMID- 16578163
TI  - The Variation of Infectivity: II.

PMID- 16578164
TI  - Strain Specificity and Production of Antibiotic Substances: VI. Strain Variation
      and Production of Streptothricin by Actinomyces Lavendulae.

PMID- 16578165
TI  - Pure Strain Mice Born to Hybrid Mothers Following Ovarian Transplantation.

PMID- 16578166
TI  - Experiments on Sexual Isolation in Drosophila: V. The Effect of Varying
      Proportions of Drosophila Pseudoobscura and Drosophilia Persimilis on the
      Frequency of Insemination in Mixed Populations.

PMID- 16578167
TI  - The Three-Dimensional Shapes of Bubbles in Foams.

PMID- 16578168
TI  - Genetic Analysis of the Induction of Tumors by Methylcholanthrene: XI. Germinal
      Mutations and Other Sudden Biological Changes Following the Subcutaneous
      Injection of Methylcholanthrene.

PMID- 16578169
TI  - Damping of Epidemic Waves.

PMID- 16578170
TI  - Topological Methods in the Theory of Functions of a Single Complex Variable: I.
      Deformation Types of Locally Simple Plane Curves.

PMID- 16578171
TI  - Topological Methods in the Theory of Functions of a Complex Variable: II.
      Boundary Values and Integral Characteristics of Interior Transformations and
      Pseudo-Harmonic Functions.

PMID- 16578172
TI  - Absolute Scalar Invariants and the Isometric Correspondence of Riemann Spaces.

PMID- 16578173
TI  - Bernoulli's Numbers and Certain Arithmetic Quotient Functions.

PMID- 16578175
TI  - Universal Rational Functions.

PMID- 16578174
TI  - The Total Differential Equation for the Exponential Function in Non-Commutative
      Normed Linear Rings.

PMID- 16578176
TI  - A New Eye Color Mutant in the Mouse with Asymmetrical Expression.

PMID- 16578177
TI  - On Non-Linear Phenomenon on Self-Rolling.

PMID- 16578178
TI  - Effects of Exposure to Ultra-Violet Light on Subsequent Dark Adaptation.

PMID- 16578179
TI  - Carbon Dioxide Utilization in the Synthesis of Acetic and Butyric Acids by
      Butyribacterium Rettgeri.

PMID- 16578180
TI  - Pollen-Tube Growth in Intergeneric Pollinations on Datura Stramonium.

PMID- 16578181
TI  - Cycles in Measles and Chicken Pox.

PMID- 16578182
TI  - On Certain Sequences of Functions.

PMID- 16578183
TI  - The Fundamental Theorem on Quadratic First Integrals.

PMID- 16578185
TI  - Intrinsic Area.

PMID- 16578184
TI  - Converse Theory of Gnomic and Equiareal Perspectivities.

PMID- 16578186
TI  - The Mean Convergence of Orthogonal Series of Polynomials.

PMID- 16578187
TI  - Influence of Hydrostatic Pressure on the Denaturation of Staphylococcus Antitoxin
      at 65 degrees C.

PMID- 16578188
TI  - A Comparison Between the Position Effects of Normal and Mutant Alleles.

PMID- 16578189
TI  - Linkage in the Albino Chromosome of the Rat.

PMID- 16578191
TI  - On the Number of Solutions of Some General Types of Equations in a Finite Field.

PMID- 16578192
TI  - Prime Number of Conjugate Operators in a Group.

PMID- 16578190
TI  - Induced Mutations and Possible Mechanisms of the Transmission of Heredity in
      Escherichia Coli.

PMID- 16578193
TI  - Experiments on Sexual Isolation in Drosophila: VI. Isolation Between Drosophila
      Pseudoobscura and Drosophila Persimilis and Their Hybrids.

PMID- 16578194
TI  - Inherited Differences in Sensitivity to Radiation in Escherichia Coli.

PMID- 16578196
TI  - An Extension of Schuster's Integral.

PMID- 16578195
TI  - A New Gene Theory and an Explanation of the Phenomenon of Dominance to Mendelian
      Segregation of the Cytogene.

PMID- 16578197
TI  - Reverse-Mutation and Adaptation in Leucineless Neurospora.

PMID- 16578198
TI  - Varieties and Mating Types in Paramecium Bursaria: I. New Variety and Types, from
      England, Ireland, and Czechoslovakia.

PMID- 16578199
TI  - On Blocks of Characters of Groups of Finite Order: I.

PMID- 16578200
TI  - The Rate of Growth of Analytic Functions.

PMID- 16578202
TI  - On the Stability of Systems of Differential Equations.

PMID- 16578201
TI  - A Generalization of the Hopf Invariant.

PMID- 16578204
TI  - A New Type of Isolating Mechanism in Drosophila.

PMID- 16578203
TI  - On Natural Auto-Antibodies as Evidenced by Anti-Venin in Serum and Liver Extract
      of the Gila Monster.

PMID- 16578205
TI  - Hybridization Between Rana Palustris and Different Geographical Forms of Rana
      Pipiens.

PMID- 16578206
TI  - On A Theorem of von Neumann.

PMID- 16578207
TI  - On Blocks of Characters of Groups of Finite Order: II.

PMID- 16578208
TI  - Effects of Exposure to Ultra-Violet Light on Human Dark Adaptation.

PMID- 16578209
TI  - Experiments on Sexual Isolation in Drosophila: VIII. Influence of Light on the
      Mating Behavior of Drosophila Subobscura, Drosophila Persimilis and Drosophila
      Pseudoobscura.

PMID- 16578211
TI  - On a Theory of Gelfand and Neumark.

PMID- 16578210
TI  - Note on the Location of the Zeros of the Derivative of a Rational Function Having
      Prescribed Symmetry.

PMID- 16578212
TI  - Prevention of Adrenal Cortical Carcinoma by Diethylstilbestrol.

PMID- 16578213
TI  - The Genetic Control of Growth Metabolism.

PMID- 16578214
TI  - Leafhopper Transmission of Corn Stunt.

PMID- 16578216
TI  - On the Singular Solutions of Certain Differential Equations of the Second Order.

PMID- 16578215
TI  - Some Properties of a Genetic Cytoplasmic Factor in Paramecium.

PMID- 16578217
TI  - Finitely Additive Set Functions and Stochastic Processes.

PMID- 16578218
TI  - Mutations Involving the Requirement of Uracil in Clostridium.

PMID- 16578219
TI  - Inheritance of Sex in Fungi.

PMID- 16578220
TI  - Detachment Frequency of Attached-X Chromosomes in Autosomal Structural
      Heterozygotes of Drosophila Melanogaster.

PMID- 16578221
TI  - The Frequency of X-Ray-Induced Chromatid Breaks in Tradescantia as Modified by
      Near Infrared Radiation.

PMID- 16578222
TI  - Reaction and Scattering Cross-Sections.

PMID- 16578223
TI  - Algebraic Matric Groups.

PMID- 16578224
TI  - The Picard-Vessiot Theory of Homogeneous Linear Ordinary Differential Equations.

PMID- 16578225
TI  - A Characterization of a Simple Plane Web.

PMID- 16578226
TI  - Cyclotomy and Trinomial Equations in a Finite Field.

PMID- 16578227
TI  - On Some Special Trinomial Equations in a Finite Field.

PMID- 16578228
TI  - A Partial Differential Equation of Fourth Order Connected with Rational Functions
      of a Complex Variable.

PMID- 16578229
TI  - A Reduction Theorem Concerning the Representation Problem for Frechet Varieties.

PMID- 16578231
TI  - Algebraic Topology and Integration Theory.

PMID- 16578230
TI  - On Sets of Integers Which Contain No Three Terms in Arithmetical Progression.

PMID- 16578232
TI  - Complexes of Manifolds.

PMID- 16578233
TI  - On Totally Positive Functions, LaPlace Integrals and Entire Functions of the
      LaGuerre-Polya-Schur Type.

PMID- 16578235
TI  - Theory of Harmonic Transformations.

PMID- 16578234
TI  - On the Location of the Critical Points of Harmonic Measure.

PMID- 16578236
TI  - Geometric Methods in Cohomology Theory.

PMID- 16578237
TI  - Complete Convergence and the Law of Large Numbers.

PMID- 16578238
TI  - Green's Functions for Linear Differential Systems of Infinite Order.

PMID- 16578239
TI  - Special Values of e , Cosh(kpi) and Sinh (kpi) to 136 Figures.

PMID- 16578240
TI  - A Reverse Mutation to a "Remote" Allele in the House Mouse.

PMID- 16578242
TI  - Curvature Theorems on Polar Curves.

PMID- 16578241
TI  - Chromosomes of the Mink.

PMID- 16578243
TI  - Weak Compactness in Banach Spaces: I.

PMID- 16578244
TI  - Note on the Critical Points of Harmonic Functions.

PMID- 16578245
TI  - The Production of Mutations in Staphylococcus Aureus by Irradiation of the
      Substrate.

PMID- 16578246
TI  - On the Distribution of Titanium Oxide and Carbon Stars in Our Part of the Milky
      Way.

PMID- 16578247
TI  - The Spread of Measles in the Family.

PMID- 16578248
TI  - Hybridization Between Rana Pipiens From Vermont and Eastern Mexico.

PMID- 16578249
TI  - A Uniqueness Theorem for Eigenfunction Expansions.

PMID- 16578250
TI  - On the Characteristic Classes of Riemannian Manifolds.

PMID- 16578251
TI  - On the Functional Equation.

PMID- 16578252
TI  - Blood Groups of the Rat (Rattus Norvegicus) and Their Inheritance.

PMID- 16578253
TI  - The Domestication of the Rat.

PMID- 16578254
TI  - An Expression of Hopf's Invariant as an Integral.

PMID- 16578255
TI  - Cohomology Invariants of Mappings.

PMID- 16578257
TI  - On the Maximum Partial Sum of Independent Random Variables.

PMID- 16578256
TI  - The (L)-Space of Relative Measure.

PMID- 16578258
TI  - Some Results on Additive Theory of Numbers.

PMID- 16578259
TI  - On the Multiplicity of Steady Gas Flows Having the Same Streamline Pattern.

PMID- 16578260
TI  - Turbulence as an Environmental Determinant of Relative Growth in Daphnia.

PMID- 16578261
TI  - A Direct Demonstration of the Phosphorus Cycle in a Small Lake.

PMID- 16578263
TI  - A Suppressor in Neurospora and its Use as Evidence for Allelism.

PMID- 16578262
TI  - Studies on the Biochemistry of Tetrahymena: IX. Folic Acid Components and
      Conjugates.

PMID- 16578264
TI  - X-Ray and Ultraviolet Studies on Pollen Tube Chromosome: II The Quadripartite
      Structure of the Prophase Chromosomes of Tradescantia.

PMID- 16578266
TI  - Abstract Group Generated by the Quaternion Units.

PMID- 16578265
TI  - On the Asymptotic Solution of the Differential Equation for Small Disturbances in
      a Laminar Flow.

PMID- 16578267
TI  - Limits for the Number of Solutions of Certain General Types of Equations in a
      Finite Field.

PMID- 16578268
TI  - Characteristic Coordinates for Hyperbolic Differential Equations in the Large.

PMID- 16578270
TI  - Chromosome Structural changes in Tradescantia Microspores Produced by Absorbed
      Radiophosphorus.

PMID- 16578269
TI  - Physical Curves.

PMID- 16578271
TI  - Interpolation and Uniqueness of Entire Functions.

PMID- 16578272
TI  - On a Theorem of Banach.

PMID- 16578273
TI  - The Inversion of a Generalized Laplace Transform.

PMID- 16578274
TI  - The Iodine Metabolism of Drosophila Gibberosa Studied by Means of Radioiodine I.

PMID- 16578275
TI  - On All of Mersenne's Numbers Particularly M(193).

PMID- 16578277
TI  - Critical Points of Harmonic Functions as Positions of Equilibrium in a Field of
      Force.

PMID- 16578276
TI  - New Types of Congruences Involving Bernoulli Numbers and Fermat's Quotient.

PMID- 16578278
TI  - Some Properties of Rotational Flow of a Perfect Gas.

PMID- 16578279
TI  - Reproductive Diapause in Drosophila Robusta.

PMID- 16578280
TI  - A Cytochemical Study of the Feulgen Nucleal Reaction.

PMID- 16578281
TI  - Dietary Factors in the Utilization of Homocystine.

PMID- 16578282
TI  - Linkage Among Genes Controlling Inhibition of Lysis in a Bacterial Virus.

PMID- 16578283
TI  - A Theory of Minimax.

PMID- 16578284
TI  - Galactic and Extragalactic Studies: XIX. Giant Variable Stars of the Loop Nebula
      (30 Doradus).

PMID- 16578285
TI  - A New Theory of Secondary Non-Disjunction in Female Drosophila Melanogaster.

PMID- 16578287
TI  - Boundaries of ULC Sets in Euclidean n-Space.

PMID- 16578286
TI  - The Origin of Volutin on the Chromosomes, Its Transfer to the Nucleolus, and
      Suggestions Concerning the Significance of this Phenomenon.

PMID- 16578288
TI  - Cyclotomic Power Characters and Trinomial Equations in a Finite Field.

PMID- 16578290
TI  - On Some Exponential Sums.

PMID- 16578289
TI  - The Stability of Differential Equations with Periodic Coefficients.

PMID- 16578291
TI  - On Spaces with Vanishing Low-Dimensional Homotopy Groups.

PMID- 16578292
TI  - Group Theoretical Discussion of Relativistic Wave Equations.

PMID- 16578293
TI  - Stereoscopic Acuity for Various Levels of Illumination.

PMID- 16578294
TI  - Reflection Effect in Eclipsing Binaries for a Point-Source of Light.

PMID- 16578295
TI  - The Stimulatory Action of Certain Fractions from Bacteria and Yeast on the
      Formation of a Bacterial Virus.

PMID- 16578296
TI  - Vitamin K(5) as an Inhibitor of the Growth of Fungi and of Fermentation by Yeast.

PMID- 16578297
TI  - Inactivation of Enzyme-Substrate Films by Small Doses of X-Rays.

PMID- 16578299
TI  - On the Differential Equations of Slip Flow.

PMID- 16578298
TI  - Notes on Integration: I.

PMID- 16578300
TI  - On the Stability of Nutritional Mutants of Bacteria.

PMID- 16578301
TI  - A Method for Selection of Biochemical Mutants of Neurospora.

PMID- 16578302
TI  - A Predictable Mutation in Bacteria.

PMID- 16578303
TI  - A Convexity Theorem.

PMID- 16578304
TI  - Notes on Integration: II.

PMID- 16578305
TI  - Some Preliminary Results on the Spectra of AsH(3), AsD(3) and PH(3).

PMID- 16578306
TI  - Evidence for an Interrelation in the Metabolism of Lysine, Arginine and
      Pyramidines in Neurospora.

PMID- 16578307
TI  - The Cytogenic Effect of Sonic Energy Applied Simultaneously with X-Rays.

PMID- 16578308
TI  - Rayleigh-Ritz and A. Weinstein Methods for Approximation of Eigenvalues: I.
      Operations in a Hilbert Space.

PMID- 16578309
TI  - Exponential Transforms and Appell Polynomials.

PMID- 16578310
TI  - Notes on Integration: III.

PMID- 16578311
TI  - The Preparation of Specific Adsorbents.

PMID- 16578312
TI  - The Valence-State Energy of the Bivalent Oxygen Atom.

PMID- 16578313
TI  - Acquisition of the J Substance by the Bovine Erythrocyte.

PMID- 16578314
TI  - Further Studies on the Effect of Infra-Red Radiation on X-Ray-Induced Chromatid
      Aberrations in Tradescantia.

PMID- 16578315
TI  - The Last Entry in Gauss's Diary.

PMID- 16578316
TI  - On the Theorem of Jentzsch.

PMID- 16578317
TI  - On Deviations between Theoretical and Empirical Distributions.

PMID- 16578318
TI  - On Interposition as a Cue for the Perception of Distance.

PMID- 16578320
TI  - On a Theorem of Weyl Concerning Eigenvalues of Linear Transformations I.

PMID- 16578321
TI  - On Self-Adjoint Differential Equations of Second Order.

PMID- 16578319
TI  - First Approximation of Pressure Distribution on Curved Profiles at Supersonic
      Speeds.

PMID- 16578322
TI  - The Coefficient Problem for Bounded Schlicht Functions.

PMID- 16578323
TI  - Geometry of Reduced Moment Spaces.

PMID- 16578324
TI  - On n-Dimensional Concepts of Bounded Variation, Absolute Continuity and
      Generalized Jacobian.

PMID- 16578325
TI  - Quadratic Relations Involving the Numbers of Solutions of Certain Types of
      Equations in a Finite Field.

PMID- 16578326
TI  - On the Use of Indeterminates in the Theory of Exponential Sums.

PMID- 16578327
TI  - On the Interpretation of Multi-Hit Survival Curves.

PMID- 16578328
TI  - Metabolic Exchange of Carbon Dioxide with Carboxyls and Oxidative Synthesis of
      C(4) Dicarboxylic Acids.

PMID- 16578329
TI  - Observations on the Effects of Maleic Hydrazide on Flowering of Tobacco, Maize
      and Cocklebur.

PMID- 16578330
TI  - Repeated Mutations in One Area of a Mouse Chromosome.

PMID- 16578331
TI  - Specificity of Interaction Between Identical Molecules.

PMID- 16578332
TI  - Inheritance of Sexuality in Chlamydomonas Reinhardi.

PMID- 16578333
TI  - The Homology Structure of Sphere Bundles.

PMID- 16578334
TI  - Elimination of Randomization in Certain Problems of Statistics and of the Theory
      of Games.

PMID- 16578335
TI  - On Multiplicative Properties of a Generalized Jacobi-Cauchy Cyclotomic Sum.

PMID- 16578336
TI  - The Solution of a Certain General Type of Integral Equation.

PMID- 16578337
TI  - Extraction of a Mating Reaction Inhibiting Agent from Paramecium Calkinsi.

PMID- 16578338
TI  - On the Rate of Passive Sinking of Daphnia.

PMID- 16578339
TI  - Potential Changes in Chloroplast Suspensions and in Whole Cytoplasm Preparations
      of Plant Cells on Illumination.

PMID- 16578340
TI  - The Structure of the Mo(6)Cl(14) Complex in the Crystal
      (NH(4))(2)(Mo(6)Cl(8))Cl(6).H(2)O.

PMID- 16578342
TI  - On the Multiplication of S-Functions.

PMID- 16578343
TI  - The Non-Finitizability of Impredicative Principles.

PMID- 16578341
TI  - Factors Governing Sexual Selection as an Isolating Mechanism in the Poeciliid
      Fish Lebistes Reticulatus.

PMID- 16578344
TI  - Electromagnetic Ponderomotive Forces within Material Bodies.

PMID- 16578345
TI  - Infra-Red Bands in the Spectrum of NH(3).

PMID- 16578346
TI  - Electron Transfer in Intermetallic Compounds.

PMID- 16578347
TI  - Various Kernels in the Theory of Partial Differential Equations.

PMID- 16578348
TI  - Multiplicative Transpormations.

PMID- 16578349
TI  - Extensive Games.

PMID- 16578350
TI  - The Theory of Micro-Meteorites: Part I. In an Isothermal Atmosphere.

PMID- 16578351
TI  - Limitation of Electron Density by the Patterson Function.

PMID- 16578352
TI  - Some Linear Operators in the Theory of Partial Differential Equations.

PMID- 16578353
TI  - Generalized Group Algebras.

PMID- 16578354
TI  - Limit Cycles of Systems of the Second Order.

PMID- 16578355
TI  - On the Addition and Multiplication Theorems for Special Functions.

PMID- 16578356
TI  - On the Boundary Behavior of Minimal Surfaces.

PMID- 16578357
TI  - The Connectedness of the Orthogonal Group in Hilbert Space.

PMID- 16578358
TI  - A Class of Soluble Diophantine Equations.

PMID- 16578360
TI  - On the Functional Equations of the Dirichlet Series Derived from Siegel Modular
      Forms.

PMID- 16578359
TI  - The Determination of Crystal Structures from X-Ray Data Without a Knowledge of
      the Phases of the Fourier Coefficients.

PMID- 16578361
TI  - The Structure of Alternative Division Rings.

PMID- 16578362
TI  - Hausdorff Measure and Lebesgue Area.

PMID- 16578363
TI  - On the Structure of Extremal Polynomials.

PMID- 16578364
TI  - The Spectrum of Capella.

PMID- 16578365
TI  - Complex Spaces With Transitive Commutative Groups of Transformations.

PMID- 16578367
TI  - Representations of Semisimple Lie Groups: II.

PMID- 16578366
TI  - On the Existence of a Basis for Every Finite Abelian Group.

PMID- 16578368
TI  - Representations of Semisimple Lie Groups: III. Characters.

PMID- 16578369
TI  - On the Numerical Computation of Mapping Functions by Orthogonalization.

PMID- 16578370
TI  - Finite Fourier Series and Cyclotomy.

PMID- 16578372
TI  - On the Evolution of the Protoplanets.

PMID- 16578371
TI  - Complete Fields From Local Rings.

PMID- 16578373
TI  - Effective Conformal Transformation of Smooth, Simply Connected Domains.

PMID- 16578374
TI  - Partial Sums of Fourier Series.

PMID- 16578376
TI  - On a Conjecture of Murray and von Neumann.

PMID- 16578375
TI  - The Mathematics of Second Quantization.

PMID- 16578377
TI  - On Determinants and a Property of the Trace in Finite Factors.

PMID- 16578378
TI  - A Generalization of the Frobenius Reciprocity Theorem.

PMID- 16578379
TI  - Heat Conduction on Riemannian Manifolds: II: Heat Distribution on Complexes and
      Approximation Theory.

PMID- 16578381
TI  - The Dimensions of the Irreducible Representations of a Finite Group.

PMID- 16578380
TI  - A Generalization of Hermite's Law of Reciprocity.

PMID- 16578382
TI  - Approximations Exceeding 1300 Decimals for radical3, 1/ radical3, Sin (pi/3) and
      Distribution of Digits in Them.

PMID- 16578383
TI  - On the Green's Functions of Quantized Fields: I.

PMID- 16578384
TI  - On the Green's Functions of Quantized Fields: II.

PMID- 16578385
TI  - Propagation of Spherical Shock Waves in Stellar Interiors.

PMID- 16578386
TI  - The Transfer of Radioactive Phosphorus From Parental to Progeny Phage.

PMID- 16578387
TI  - A Single-Cell Analysis of the Transmission of Enzyme-Forming Capacity in Yeast.

PMID- 16578388
TI  - The Class-Number of Real Quadratic Fields.

PMID- 16578389
TI  - On The Basis Theorem for Finite Abelian Groups (Second Note).

PMID- 16578390
TI  - Fourier Analysis and Symmetric Spaces.

PMID- 16578392
TI  - On the Consistency of "New Foundations".

PMID- 16578391
TI  - Remarks on the Lebesgue's Measure Extension Device for Finitely Additive Boolean
      Lattices.

PMID- 16578393
TI  - Growth Responses of Opposite Sign Among Different Neuron Types Exposed to Thyroid
      Hormone.

PMID- 16578394
TI  - Forty-Four New White Dwarfs in the Southern Hemisphere.

PMID- 16578395
TI  - Alternative Amino Acid Requirements in Auxotrophic Mutants of Salmonella
      Typhimurium.

PMID- 16578396
TI  - Accumulation of Anthranilic Acid by a Mutant of Maize.

PMID- 16578397
TI  - Properties of Mutants of Drosophila Melanogaster and Changes During Development
      as Revealed by Paper Chromatography.

PMID- 16578398
TI  - Young Produced from Ovaries Subjected to Endocrine Imbalance.

PMID- 16578399
TI  - Improving the Readability of Typewritten Manuscripts.

PMID- 16578400
TI  - On The Invariants of Finite Abelian Groups.

PMID- 16578401
TI  - On Finite Groups with Two Independent Generators: II.

PMID- 16578402
TI  - Representations of Semisimple Lie Groups: IV.

PMID- 16578403
TI  - On The Modular Representations of the Symmetric Group.

PMID- 16578404
TI  - Note on Association of Attributes.

PMID- 16578405
TI  - Tensorfields and Ricci Curvature in Hermitian Metric.

PMID- 16578407
TI  - Passive Total Systems with Constant Coefficients.

PMID- 16578406
TI  - On The Formal Expansion of Operator Functions in Terms of a Set of Basic
      Operators.

PMID- 16578409
TI  - On the Origin of the Irregular Satellites.

PMID- 16578408
TI  - An Improvement of an Inequality of Minkowski.

PMID- 16578410
TI  - The Origin of Phosphorus in T5 Bacteriophage of Escherichia Coli.

PMID- 16578411
TI  - The Extended Onsager Equation.

PMID- 16578412
TI  - Configurations of Polypeptide Chains With Favored Orientations Around Single
      Bonds: Two New Pleated Sheets.

PMID- 16578413
TI  - Hybrids Between Lycopersicon Esculentum Mill. And Solanum Lycopersicoides Dun.

PMID- 16578414
TI  - A Majorant Method For Non-Linear Partial Differential Equations.

PMID- 16578415
TI  - On Finite Groups With Two Independent Generators: III. Exponential Substitutions.

PMID- 16578416
TI  - Maximum Properties and Inequalities for the Eigenvalues of Completely Continuous
      Operators.

PMID- 16578417
TI  - Invariant Differential Forms in Several Group Variables as Solutions of Partial
      Differential Equations in Frechet Differentials.

PMID- 16578418
TI  - Representation of Nucleon-Nucleon Singlet S Scattering.

PMID- 16578419
TI  - Kappa Concentration per Cell in Relation to the Life Cycle, Genotype and Mating
      Type in Paramecium Aurelia, Variety 4.

PMID- 16578421
TI  - Representations by Cubic Congruences.

PMID- 16578420
TI  - Mating Type Determination in Paramecium Aurelia, a Model of Nucleo-Cytoplasmic
      Interaction.

PMID- 16578422
TI  - Almost Periodic Functions on Locally Compact Groups.

PMID- 16578423
TI  - Organismal Differentials and Organ Differentials.

PMID- 16578424
TI  - Comparison of the Phosphorus Content, Optical Rotation, Separation of Hemes and
      Globin, and Terminal Amino Acid Residurs of Normal Adult Human Hemoglobin and
      Sickle Cell Anemia Hemoglobin.

PMID- 16578425
TI  - Electrophoretic Studies of Globins Prepared From Normal Adult and Sickle Cell
      Hemoglobins.

PMID- 16578426
TI  - The Effect of Ammonia on Morphogenesis in the Acrasieae.

PMID- 16578427
TI  - Biometric Evidence of Natural Selection in Asclepias Tuberosa.

PMID- 16578428
TI  - A Study of Lignin Formation Based on the Oxidation of Native and Enzymatically
      Liberated Lignins.

PMID- 16578429
TI  - A Proposed Structure For The Nucleic Acids.

PMID- 16578430
TI  - Induced Dominant Lethality in Lilium.

PMID- 16578431
TI  - The Metabolism of Isoprenoid Precursors in a Plant System.

PMID- 16578432
TI  - The Production of Mutations in Drosophila by Tertiary-Butyl Hydroperoxide.

PMID- 16578433
TI  - The Antigens Determined by the H-2 Locus: A Rhesus-Like System in the Mouse.

PMID- 16578434
TI  - Production of Mitotic Abnormalities by Ribonuclease.

PMID- 16578435
TI  - Diffusion of Chromogenic Inductors of Serratia Marcescens.

PMID- 16578436
TI  - Inheritance of Mating Type and a Lethal Factor in Cosmarium Botrytis Var.
      Subtumidum Wittr.

PMID- 16578437
TI  - A Factor (or Mutator Gene) Influencing Mutation Rates in Escherichia Coli.

PMID- 16578438
TI  - Equations in Finite Fields.

PMID- 16578439
TI  - Monotone Approximation in Dynamic Programming and the Calculus of Variations.

PMID- 16578440
TI  - Representations of Semisimple Lie Groups: V.

PMID- 16578441
TI  - Representations of Semisimple Lie Groups: VI.

PMID- 16578442
TI  - Spontaneous Testicular Teratomas in an Inbred Strain of Mice.

PMID- 16578443
TI  - Physics and Physiology of Neutron-Capture Therapy.

PMID- 16578444
TI  - THE EFFECT OF THIOCTIC ACID ON THE QUANTUM EFFICIENCY OF THE HILL REACTION IN
      INTERMITTENT LIGHT.

PMID- 16578445
TI  - MAGNESIUM ANTAGONISM OF THE UNCOUPLING OF OXIDATIVE PHOSPHORYLATION BY IODO
      THYRONINES.

PMID- 16578446
TI  - ALLELIC STRAINS OF Neurospora LACKING TRYPTOPHAN SYNTHETASE: A PRELIMINARY
      IMMUNOCHEMICAL CHARACTERIZATION.

PMID- 16578447
TI  - ON ABELIAN VARIETIES OVER FUNCTION FIELDS.

PMID- 16578448
TI  - THE STRONG LAW OF LARGE NUMBERS WHEN THE FIRST MOMENT DOES NOT EXIST.

PMID- 16578449
TI  - CESARO SUMMABILITY OF WALSH-FOURIER SERIES.

PMID- 16578450
TI  - GENERALIZED DERIVATIVES AND EXPANSIONS.

PMID- 16578451
TI  - ON THE MODULAR REPRESENTATIONS OF THE SYMMETRIC GROUP VI.

PMID- 16578453
TI  - NECESSARY AND SUFFICIENT CONDITIONS FOR CARLSON'S THEOREM ON ENTIRE FUNCTIONS.

PMID- 16578452
TI  - THE VALIDITY OF KRON'S METHOD OF TEARING.

PMID- 16578454
TI  - SCIENCE AND BROAD POINTS OF VIEW.

PMID- 16578455
TI  - THE ENZYMATIC ACTIVATION OF AMINO ACIDS VIA THEIR ACYL-ADENYLATE DERIVATIVES.

PMID- 16578456
TI  - ENZYMATIC SYNTHESIS OF URIDINE DIPHOSPHATE XYLOSE AND URIDINE DIPHOSPHATE
      ARABINOSE.

PMID- 16578458
TI  - SUPPRESSION OF BUNT-RESISTANT GENE ACTION BY ENVIRONMENTAL CONDITIONS.

PMID- 16578457
TI  - RULES FOR TESTING STABILITY OF A SELECTIVE POLYMORPHISM.

PMID- 16578459
TI  - OPEN MAPPINGS OF COMPACT CONTINUA.

PMID- 16578460
TI  - CONCERNING THE ACTION OF A FINITE GROUP.

PMID- 16578461
TI  - A DIFFUSION EQUIVALENT TO A COUNTABLE MARKOV CHAIN.

PMID- 16578462
TI  - ON DIFFERENTIAL GEOMETRY AND HOMOGENEOUS SPACES. II.

PMID- 16578463
TI  - THE DEGREE OF AN IRREDUCIBLE REPRESENTATION OF S(n).

PMID- 16578464
TI  - ON A GENERALIZATION OF THE NOTION OF MANIFOLD.

PMID- 16578465
TI  - THE KINETIC ENERGY OF RELATIVE MOTION.

PMID- 16578466
TI  - RADIOACTIVE STRONTIUM FALLOUT.

PMID- 16578467
TI  - SPECTROPHOTOMETRIC EXAMINATION OF HYDROGENASE AND NITROGENASE IN SOYBEAN NODULES
      AND Azotobacter.

PMID- 16578468
TI  - OPTICALLY ACTIVE COMPOUNDS FROM RACEMIC MIXTURES BY MEANS OF RANDOM DISTRIBUTION.

PMID- 16578470
TI  - ARE ALL PRODUCTS OF SPERMATOGENESIS REGULARLY FUNCTIONAL?

PMID- 16578469
TI  - THE GENETIC CONTROL OF ADENYLOSUCCINASE IN Neurospora Crassa.

PMID- 16578471
TI  - SHORTENING OF LIFE IN THE OFFSPRING OF MALE MICE EXPOSED TO NEUTRON RADIATION
      FROM AN ATOMIC BOMB.

PMID- 16578473
TI  - A UNIFIED THEORY OF GENERAL RELATIVITY OF GRAVITATION AND ELECTROMAGNETISM. IV.

PMID- 16578472
TI  - CORRELATED SELECTION FOR MOTILITY AND SEX-INCOMPATIBILITY IN Escherichia Coli
      K12.

PMID- 16578474
TI  - INTEGRATION OVER HILBERT SPACE AND OUTER EXTENSIONS.

PMID- 16578475
TI  - FACTORIZATION IN THE GROUP ALGEBRA OF THE REAL LINE.

PMID- 16578476
TI  - SPECIFICITY OF THE LONDON-EISENSCHITZ WANG FORCE.

PMID- 16578477
TI  - THE AUDITORY SENSITIVITY OF THE ATLANTIC GRASSHOPPER.

PMID- 16578478
TI  - SOME EFFECTS OF ALTERNATION RATE IN A TIME-CORRELATED REINFORCEMENT CONTINGENCY.

PMID- 16578479
TI  - TRANSPLANTATIONS OF THE EMBRYONIC CHICK FOREBRAIN REGION BEFORE ESTABLISHMENT OF
      CIRCULATION.

PMID- 16578480
TI  - CENTIMETER WAVELENGTH RADIO ASTRONOMY INCLUDING OBSERVATIONS USING THE MASER.

PMID- 16578481
TI  - THE CONTROL OF THE FORMATION OF SPECIFIC PROTEINS IN BACTERIA AND IN ANIMAL
      CELLS.

PMID- 16578482
TI  - THE MOLECULAR BASIS OF ANTIBODY FORMATION.

PMID- 16578483
TI  - PURIFICATION OF A NERVE-GROWTH PROMOTING PROTEIN FROM THE MOUSE SALIVARY GLAND
      AND ITS NEURO-CYTOTOXIC ANTISERUM.

PMID- 16578485
TI  - STUDIES ON SOLUBLE RIBONUCLEIC ACID (S-RNA) OF RABBIT LIVER, I. AMINO ACID
      ACCEPTOR SPECIFICITY AND MOLECULAR WEIGHT.

PMID- 16578484
TI  - THE ACCOMMODATION OF NONCOMPLEMENTARY BASES IN HELICAL POLYRIBONUCLEOTIDES AND
      DEOXYRIBONUCLEIC ACIDS.

PMID- 16578486
TI  - THE MECHANISM OF BACTERIAL FRAGILITY PRODUCED BY 5-FLUOROURACIL: THE ACCUMULATION
      OF CELL WALL PRECURSORS.

PMID- 16578487
TI  - ACTION SPECTRA OF CHROMATIC TRANSIENTS AND THE EMERSON EFFECT IN MARINE ALGAE.

PMID- 16578488
TI  - SIGNIFICANT STRUCTURES IN LIQUIDS, III. PARTITION FUNCTION FOR FUSED SALTS.

PMID- 16578489
TI  - SIGNIFICANT STRUCTURES IN LIQUIDS, IV. LIQUID CHLORINE.

PMID- 16578490
TI  - THE GENIC CONTROL OF MATING TYPES IN PARAMECIUM BURSARIA.

PMID- 16578492
TI  - SOME HOLOMORPHIC SEMI-GROUPS.

PMID- 16578491
TI  - THE EVOLUTIONARY IMPLICATIONS OF THE CYTOLOGICAL POLYMORPHISM AND PHYLOGENY OF
      THE VIRILIS GROUP OF DROSOPHILA.

PMID- 16578493
TI  - THE EXTENT OF ASYMPTOTIC STABILITY.

PMID- 16578494
TI  - VIRUS-CELL INTERACTION WITH A TUMOR-PRODUCING VIRUS.

PMID- 16578495
TI  - THE STABILITY OF NON-DISSIPATIVE COUETTE FLOW IN THE PRESENCE OF AN AXIAL
      MAGNETIC FIELD.

PMID- 16578496
TI  - EXCESSIVE GROWTH OF THE SYMPATHETIC GANGLIA EVOKED BY A PROTEIN ISOLATED FROM
      MOUSE SALIVARY GLANDS.

PMID- 16578497
TI  - DESTRUCTION OF THE SYMPATHETIC GANGLIA IN MAMMALS BY AN ANTISERUM TO A NERVE
      GROWTH PROTEIN.

PMID- 16578498
TI  - INTERACTION OF SMALL IONS AND MOLECULES WITH RIBONUCLEIC ACID.

PMID- 16578499
TI  - THE MECHANISM OF THE DE NOVO SYNTHESIS OF POLYSACCHARIDE BY PHOSPHORYLASE.

PMID- 16578501
TI  - A MATHEMATICAL AID IN OPTIMIZING ENGINEERING DESIGNS.

PMID- 16578500
TI  - SIGNIFICANT LIQUID STRUCTURES, VI. THE VACANCY THEORY OF LIQUIDS.

PMID- 16578502
TI  - EXTRA-TERRESTRIAL LIFE.

PMID- 16578503
TI  - UNIFORM CONVERGENCE OF MONOTONE SEQUENCES OF FUNCTIONS.

PMID- 16578504
TI  - SOME ASPECTS OF THE FERMAT PROBLEM (SECOND PAPER).

PMID- 16578505
TI  - GENERALIZED INVARIANT IMBEDDING RELATION.

PMID- 16578506
TI  - THE GEOMETRY OF COILING IN GASTROPODS.

PMID- 16578507
TI  - PROLONGATION OF THE LIFE SPAN OF KOKANEE SALMON (ONCORHYNCHUS NERKA KENNERLYI) BY
      CASTRATION BEFORE BEGINNING OF GONAD DEVELOPMENT.

PMID- 16578508
TI  - THERMODYNAMIC POTENTIALS OF SYMMETRICAL ELECTROLYTES.

PMID- 16578509
TI  - ON THE CLASS NUMBER OF REAL QUADRATIC FIELDS.

PMID- 16578510
TI  - ASYMPTOTIC BEHAVIOR AND PERIODIC SOLUTIONS OF A NONLINEAR DIFFERENTIAL-DIFFERENCE
      EQUATION.

PMID- 16578511
TI  - A METHOD FOR DEFINING PRINCIPAL MODES OF NONLINEAR SYSTEMS UTILIZING INFINITE
      DETERMINANTS, II.

PMID- 16578512
TI  - NOTE ON HYDROMAGNETIC WAVES IN A COMPRESSIBLE FLUID CONDUCTOR.

PMID- 16578513
TI  - ON A SHORT-LIVED COSMIC RAY DECREASE ON NOVEMBER 13, 1960.

PMID- 16578514
TI  - EVIDENCE CONCERNING LIQUID STRUCTURE.

PMID- 16578516
TI  - THE CRYSTAL STRUCTURES OF WOLLASTONITE AND PECTOLITE.

PMID- 16578515
TI  - ON THE CONTAINMENT TIME OF A PLASMA: AN IMPORTANT ERROR.

PMID- 16578517
TI  - ON BLOCKS OF REPRESENTATIONS OF FINITE GROUPS.

PMID- 16578518
TI  - INVESTIGATION ON GROUPS OF EVEN ORDER, I.

PMID- 16578519
TI  - ON THE MAXIMAL ERGODIC THEOREM.

PMID- 16578520
TI  - HEAT-RESISTANCE OF THE TUMORIGENIC NUCLEIC ACID OF SHOPE PAPILLOMATOSIS.

PMID- 16578521
TI  - THE BOMBARDMENT OF SOLID D(2)O BY LOW-ENERGY ELECTRONS UNDER ASTRONOMICAL
      CONDITIONS.

PMID- 16578522
TI  - DECABORANE (16): ITS REARRANGEMENT TO DECABORANE (14) AND CLEAVAGE.

PMID- 16578523
TI  - RADIATION DAMAGE IN ORGANIC CRYSTALS: AUFBAU PROCESSES.

PMID- 16578524
TI  - SIGNIFICANT LIQUID STRUCTURE THEORY, IX. PROPERTIES OF DENSE GASES AND LIQUIDS.

PMID- 16578525
TI  - COMMENTS ON A PAPER DEALING WITH HYDROMAGNETIC STABILITY OF A PLASMA.

PMID- 16578526
TI  - A FURTHER MATHEMATICAL AID IN OPTIMIZING ENGINEERING DESIGNS.

PMID- 16578527
TI  - EFFECT OF THE RIGIDITY OF THE INNER CORE ON THE FUNDAMENTAL OSCILLATION OF THE
      EARTH.

PMID- 16578529
TI  - COMPLETE STABILITY OF A NONLINEAR CONTROL SYSTEM.

PMID- 16578531
TI  - THE ROLE OF GRAVITATION IN THE CREATION OF MATTER.

PMID- 16578528
TI  - CANONICAL STRUCTURE OF LINEAR DYNAMICAL SYSTEMS.

PMID- 16578530
TI  - EXTERIOR ALGEBRA AND THE ACTION PRINCIPLE, I.

PMID- 16578532
TI  - NATIONAL ACADEMY OF SCIENCES: OFFICERS, COUNCIL, MEMBERS, FORIEGN ASSOCIATES, AND
      SECTIONS.

PMID- 16578533
TI  - ON THE CONSTRUCTION OF CERTAIN LIAPUNOV FUNCTIONS.

PMID- 16578534
TI  - INTRACHROMOSOMAL EXCHANGE AT THE BAR LOCUS IN DROSOPHILA.

PMID- 16578535
TI  - ANALYSIS OF UNLINKED SUPPRESSORS OF AN O degrees MUTATION IN SALMONELLA.

PMID- 16578536
TI  - THE ENZYMATIC METHYLATION OF RNA AND DNA, II. ON THE SPECIES SPECIFICITY OF THE
      METHYLATION ENZYMES.

PMID- 16578537
TI  - STABILITY OF NITROGEN-FIXING ENZYMES AND THE REACTIVATION OF A COLD LABILE
      ENZYME.

PMID- 16578539
TI  - VARIATIONAL BOUNDARY VALUE PROBLEMS FOR QUASI-LINEAR ELLIPTIC EQUATIONS OF
      ARBITRARY ORDER.

PMID- 16578540
TI  - THE IONIC CENTRIFUGE CAN GIVE FUSION NUCLEAR POWER.

PMID- 16578538
TI  - SEPARATION OF THE BIOSYNTHESIS OF THE ANTIBIOTIC POLYPEPTIDE TYROCIDINE FROM
      PROTEIN BIOSYNTHESIS.

PMID- 16578541
TI  - PHYSICAL AND CHEMICAL PROPERTIES OF RNA FROM THE BACTERIAL VIRUS R17.

PMID- 16578542
TI  - SIMPLIFICATION OF MAPPINGS.

PMID- 16578543
TI  - ON MATERIALS OF HIGH DIELECTRIC CONSTANT.

PMID- 16578544
TI  - ON THE NUCLEI OF A SIMPLE JORDAN ALGEBRA.

PMID- 16578545
TI  - RELATIVISTIC SURFACE DYNAMICS OF AN ISOLATED WORLD TUBE OF PERFECT FLUID.

PMID- 16578546
TI  - INTERMOLECULAR FORCES AND BIOLOGICAL SPECIFICITY.

PMID- 16578547
TI  - ON THE ABSOLUTE STABILITY OF SAMPLED-DATA CONTROL SYSTEMS.

PMID- 16578548
TI  - VARIATIONAL BOUNDARY VALUE PROBLEMS FOR QUASI-LINEAR ELLIPTIC EQUATIONS, II.

PMID- 16578549
TI  - ANALYSIS OF A NEW FORMALISM IN PERTURBATION THEORY.

PMID- 16578550
TI  - A NOTE ON THE DISTRIBUTION OF SUMS OF INDEPENDENT RANDOM VARIABLES.

PMID- 16578551
TI  - MODELS OF THE FUNDAMENTAL THEOREM OF ARITHMETIC.

PMID- 16578553
TI  - THE DEPENDENCE OF THE SCHOENFLIES EXTENSION ON AN ACCESSORY PARAMETER (THE
      TOPOLOGICAL CASE).

PMID- 16578552
TI  - REPLICATIVE FRAGMENTATION IN T4 PHAGE: INHIBITION BY CHLORAMPHENICOL.

PMID- 16578554
TI  - ON A "MONOTONICITY" METHOD FOR THE SOLUTION OF NONLINEAR EQUATIONS IN BANACH
      SPACES.

PMID- 16578555
TI  - SPECTRAL OPERATORS IN A DIRECT SUM OF HILBERT SPACES.

PMID- 16578557
TI  - THE INDEPENDENCE OF THE CONTINUUM HYPOTHESIS.

PMID- 16578556
TI  - A CHARACTERIZATION OF LEXICOGRAPHICALLY ORDERED eta(alpha)-SETS.

PMID- 16578559
TI  - INTRODUCTION.

PMID- 16578558
TI  - ERGODIC THEORY, GROUP THEORY AND DIFFERENTIAL GEOMETRY.

PMID- 16578560
TI  - COMMUNICATION AND COMPREHENSION OF SCIENTIFIC KNOWLEDGE.

PMID- 16578561
TI  - THE ROLE OF SCIENCE IN UNIVERSITIES, GOVERNMENT, AND INDUSTRY: SCIENCE AND PUBLIC
      POLICY.

PMID- 16578562
TI  - SYNTHESIS AND APPLICATIONS OF SCIENTIFIC KNOWLEDGE FOR HUMAN USE.

PMID- 16578563
TI  - SCIENCE AND THE SATISFACTION OF HUMAN ASPIRATIONS.

PMID- 16578564
TI  - A GLOBAL EXISTENCE THEOREM FOR SOME DIFFERENTIAL EQUATIONS IN HILBERT SPACES.

PMID- 16578565
TI  - H = W.

PMID- 16578566
TI  - MEAN-SQUARE MOMENTS OF CHAIN MOLECULES.

PMID- 16578567
TI  - TESTS FOR A GENE-DEPENDENT CYTOPLASMIC PARTICLE ASSOCIATED WITH R PARAMUTATION IN
      MAIZE.

PMID- 16578569
TI  - ON THE STRUCTURE OF COMPACT COMPLEX ANALYTIC SURFACES, II.

PMID- 16578568
TI  - ACTIVATION OF PROTEIN SYNTHESIS IN THE IMBIBITION PHASE OF SEED GERMINATION.

PMID- 16578571
TI  - WEIGHTING PATTERNS AND THE CONTROLLABILITY AND OBSERVABILITY OF LINEAR SYSTEMS.

PMID- 16578570
TI  - KINEMATIC STABILIZATION OF CONTINUOUS-FLOW ELECTROPHORESIS AGAINST THERMAL
      CONVECTION.

PMID- 16578572
TI  - THE RECTANGULARITY LAW OF TRANSFORMERS.

PMID- 16578573
TI  - THE ABUNDANCES OF IRON AND SILICON IN THE SUN.

PMID- 16578574
TI  - THE NATURE OF AITKEN CONDENSATION NUCLEI IN THE ATMOSPHERE.

PMID- 16578576
TI  - RANDOM POLYGONS DETERMINED BY RANDOM LINES IN A PLANE, II.

PMID- 16578575
TI  - REMARKS ON NONLINEAR FUNCTIONAL EQUATIONS.

PMID- 16578577
TI  - AVERAGES FOR POLYGONS FORMED BY RANDOM LINES.

PMID- 16578578
TI  - STUDIES OF CHLOROPLAST DEVELOPMENT IN EUGLENA, VIII. CHLOROPLAST-ASSOCIATED DNA.

PMID- 16578579
TI  - DRIFT INSTABILITIES IN CYLINDRICAL DISCHARGES INVOLVING BOTH IONS AND ELECTRONS.

PMID- 16578580
TI  - GRAVITATIONAL COLLAPSE.

PMID- 16578581
TI  - SPHERICALLY SYMMETRIC DISTRIBUTIONS OF MATTER WITHOUT PRESSURE.

PMID- 16578582
TI  - PREDATION AND RELATIVE HELMET SIZE IN CYCLOMORPHIC DAPHNIA.

PMID- 16578583
TI  - WHICH PART OF THE SAMPLE CONTAINS THE INFORMATION?

PMID- 16578584
TI  - TOPOLOGICAL MAPPING OF ORGANIC MOLECULES.

PMID- 16578585
TI  - THE ORGANIZATION OF NUCLEI AND CHROMOSOMES IN HONEYBEE EMBRYONIC CELLS.

PMID- 16578586
TI  - VOLATILE ORGANIC MATERIAL OF PLANT ORIGIN IN THE ATMOSPHERE.

PMID- 16578587
TI  - MOLECULAR COMPLEXES OF FLAVINS AND PHENOLS, III. FACTORS INFLUENCING SPECTRA AND
      STABILITY.

PMID- 16578588
TI  - CHARGE TRANSFER IN MOLECULAR CRYSTALS.

PMID- 16578589
TI  - ON ACCRETIVE BOUNDARY PROBLEMS OF THE SECOND ORDER.

PMID- 16578590
TI  - CONFORMATION OF AN ISOLATED POLYMER MOLECULE AT AN INTERFACE.

PMID- 16578591
TI  - ON THE STABILITY OF STOCHASTIC DYNAMICAL SYSTEMS.

PMID- 16578592
TI  - THE KARYOTYPE OF THE MOUSE, WITH IDENTIFICATION OF A TRANSLOCATION.

PMID- 16578593
TI  - PRODUCTION OF ACTION POTENTIALS BY THE INTERNODES OF ISOLATED MYELINATED NERVE
      FIBERS.

PMID- 16578594
TI  - ON THE RELATION BETWEEN THE PRODUCTIVITY, BIOMASS, DIVERSITY, AND STABILITY OF A
      COMMUNITY.

PMID- 16578595
TI  - A POSSIBLE ULTRASTRUCTURAL CORRELATE OF FUNCTION IN THE FROG RETINAL ROD.

PMID- 16578596
TI  - ADVANCES IN FUSION RESEARCH.

PMID- 16578597
TI  - THE APPLICATION OF SIGNIFICANT STRUCTURE THEORY TO BINARY LIQUID MIXTURES: AR +
      N(2), AR + O(2), AND O(2) + N(2).

PMID- 16578598
TI  - ASYMPTOTIC THEORY OF THE FREE TORSIONAL OSCILLATIONS OF THE EARTH.

PMID- 16578599
TI  - STABILITY AND ASYMPTOTIC FIXED-POINT THEORY.

PMID- 16578600
TI  - CLUSTER SETS AT ISOLATED AND NONISOLATED SINGULARITIES.

PMID- 16578601
TI  - LIMITS OF INFINITE POPULATIONS UNDER RANDOM MATING.

PMID- 16578602
TI  - FIXED-POINT THEOREMS FOR NONCOMPACT MAPPINGS IN HILBERT SPACE.

PMID- 16578603
TI  - A STURM-LIOUVILLE THEOREM FOR NONLINEAR ELLIPTIC PARTIAL DIFFERENTIAL EQUATIONS.

PMID- 16578604
TI  - THE ACTUAL MASS OF POTENTIAL ENERGY, II.

PMID- 16578606
TI  - ON STABILITY DEFINITIONS OF DYNAMICAL SYSTEMS.

PMID- 16578605
TI  - ON THE NATURE OF THE SPECTRUM OF THE TIME CORRELATION FUNCTION MATRIX FOR
      STOCHASTIC PROCESSES.

PMID- 16578607
TI  - KINETINLIKE FACTORS IN THE ROOT EXUDATE OF SUNFLOWERS.

PMID- 16578609
TI  - MICROLIMATIC AND VEGETATIONAL CONTRASTS WITHIN A SUBALPINE VALLEY.

PMID- 16578608
TI  - EVIDENCE FOR THE LOCALIZATION OF PLASTOCYANIN IN THE ELECTRON-TRANSPORT CHAIN OF
      PHOTOSYNTHESIS.

PMID- 16578611
TI  - EFFECT OF METHYL GROUPS UPON THE SOLVENT POWER OF ALIPHATIC LIQUIDS.

PMID- 16578610
TI  - CARRIER-MEDIATED CATION TRANSPORT IN BARLEY ROOTS: KINETIC EVIDENCE FOR A
      SPECTRUM OF ACTIVE SITES.

PMID- 16578612
TI  - THE SIGNIFICANT STRUCTURE THEORY APPLIED TO LIQUID HYDROGEN HALIDES.

PMID- 16578613
TI  - A CHARACTERIZATION OF WEIERSTRASS ANALYTIC FUNCTIONS.

PMID- 16578614
TI  - ALEXANDER-SPANIER COHOMOLOGY AND RINGS OF CONTINUOUS FUNCTIONS.

PMID- 16578615
TI  - THE HIGHER-DIMENSIONAL PLATEAU PROBLEM ON A RIEMANNIAN MANIFOLD.

PMID- 16578616
TI  - AN EXAMPLE IN NOETHERIAN RINGS.

PMID- 16578617
TI  - A COUNTEREXAMPLE IN NOETHERIAN RINGS.

PMID- 16578618
TI  - RIGIDITY OF POSITIVELY CURVED KAEHLER MANIFOLDS.

PMID- 16578619
TI  - NONEXPANSIVE NONLINEAR OPERATORS IN A BANACH SPACE.

PMID- 16578620
TI  - REGULATION OF HIBERNATING PERIODS BY TEMPERATURE.

PMID- 16578621
TI  - THE CLOSE-PACKED-SPHERON MODEL OF ATOMIC NUCLEI AND ITS RELATION TO THE SHELL
      MODEL.

PMID- 16578622
TI  - RED SHIFT DISCRETIZATION IN THE EPOCHAL COSMOLOGY.

PMID- 16578624
TI  - A FREQUENCY-MODULATED ULTRASONIC INTERFEROMETER: ADIABATIC COMPRESSIBILITY OF
      AQUEOUS SOLUTIONS OF N(A)C(L) AND KC(L) AT 25 degrees C.

PMID- 16578623
TI  - Dynamics of spherical galaxies, ii.

PMID- 16578625
TI  - Approximation by polynomials: uniform convergence as implied by mean convergence.

PMID- 16578627
TI  - Asymptotic diophantine approximations to e.

PMID- 16578626
TI  - Hereditary rings.

PMID- 16578628
TI  - Asymptotic diophantine approximations.

PMID- 16578629
TI  - A nitroxide-maleimide spin label.

PMID- 16578630
TI  - Chemical events on the primitive Earth.

PMID- 16578632
TI  - Studies in irreversible thermodynamics, v. Statistical thermodynamics of a simple
      steady-state membrane model.

PMID- 16578631
TI  - HYDROGEN ADDITION RADICALS ON RNA AND THE NUCLEIC-ACID BASES AT 77 degrees K.

PMID- 16578633
TI  - 8-azacycl(2.2.2)azine.

PMID- 16578634
TI  - Triplet excitons in polyadenylic Acid.

PMID- 16578635
TI  - The residue calculus and some transcendental results in algebraic geometry, ii.

PMID- 16578637
TI  - Uniqueness theorems for polyhedra.

PMID- 16578636
TI  - Examples of singular normal complex spaces which are topological manifolds.

PMID- 16578639
TI  - On the chern numbers of certain complex and almost complex manifolds.

PMID- 16578638
TI  - Approximation by polynomials: uniform convergence as implied by mean convergence,
      ii.

PMID- 16578640
TI  - Characterization of plane algebroid curves whose module of differentials has
      maximum torsion.

PMID- 16578641
TI  - On cluster sets of meromorphic functions.

PMID- 16578642
TI  - A geometric analogue of the electron cloud.

PMID- 16578643
TI  - On the nonpower density expansion of transport coefficients.

PMID- 16578644
TI  - Hole theory of surface tension of polymer liquids.

PMID- 16578645
TI  - Studies in irreversible thermodynamics, vii.

PMID- 16578646
TI  - Genomic function during the lampbrush chromosome stage of amphibian oogenesis.

PMID- 16578647
TI  - The induction of cellular DNA synthesis by simian virus 40 in contact-inhibited
      and in x-irradiated cells.

PMID- 16578648
TI  - SATELLITE DNA'S IN THE CRABS Gecarcinus lateralis AND Cancer pagurus.

PMID- 16578649
TI  - On the theoretical relationship between flow stress and large natural strains in
      tensile tests on steel cylinders.

PMID- 16578650
TI  - ANALYTICAL EVALUATION OF THREE- AND FOUR-CENTER INTEGRALS OF r(12) WITH SLATER
      TYPE ORBITALS.

PMID- 16578651
TI  - Burrau'S problem of three bodies.

PMID- 16578652
TI  - Confidence sequences for mean, variance, and median.

PMID- 16578653
TI  - The organic nature of atmospheric condensation nuclei.

PMID- 16578654
TI  - On obstructions to deformations of complex analytic surfaces.

PMID- 16578655
TI  - Extended dynamical systems and stability theory.

PMID- 16578656
TI  - Minimal cones, plateau's problem, and the bernstein conjecture.

PMID- 16578657
TI  - A class of nonautonomous differential equations reducible to autonomous ones by
      an exact method.

PMID- 16578658
TI  - Silica glass: a bent-bond model.

PMID- 16578659
TI  - Phase transition in a one-dimensional system, ii.

PMID- 16578660
TI  - KINETICS OF PHYTOCHROME CONVERSION: MULTIPLE PATHWAYS IN THE P(r) TO P(fr)
      REACTION, AS STUDIED BY DOUBLE-FLASH TECHNIQUE.

PMID- 16578661
TI  - A boundary condition for a holomorphic function in a jordan region to be
      schlicht.

PMID- 16578662
TI  - BEHAVIORAL MUTANTS OF Drosophila ISOLATED BY COUNTERCURRENT DISTRIBUTION.

PMID- 16578664
TI  - Characterization and extension of generalized harmonizable random fields.

PMID- 16578663
TI  - The biosynthesis of tobacco mosaic virus RNA: relationships to the biosynthesis
      of virus-specific ribonuclease-resistant RNA.

PMID- 16578665
TI  - THE GENETIC STRUCTURE OF THE INCOMPATIBILITY FACTORS OF Schizophyllum commune:
      THREE FUNCTIONALLY DISTINCT CLASSES OF B FACTORS.

PMID- 16578666
TI  - Function of the "quantasome" in photosynthesis: structure and properties of
      membrane-bound particle active in the dark reactions of photophosphorylation.

PMID- 16578667
TI  - Introduction.

PMID- 16578668
TI  - Derivation of an Earth model from free oscillation data.

PMID- 16578669
TI  - The crystal structure of the mineral pollucite.

PMID- 16578670
TI  - ON BRIDGMAN'S OBSERVATIONAL RELATIONSHIP BETWEEN THE RATIO a/R AND THE NATURAL
      STRAIN IN TENSILE TESTS ON STEEL CYLINDERS.

PMID- 16578671
TI  - A method for separating according to mass a mixture of macromolecules or small
      particles suspended in a fluid, I. Theory.

PMID- 16578672
TI  - Electrohydrodynamic waves and related phenomena.

PMID- 16578673
TI  - The effect of pressure on the mossbauer resonance in hemin and iron
      phthalocyanine.

PMID- 16578674
TI  - Spin-labeled nucleic acids.

PMID- 16578675
TI  - Pressure and hydration effects on chemically reacting systems in the
      ultracentrifuge.

PMID- 16578676
TI  - The precursor of the thymine dimer in ice.

PMID- 16578677
TI  - A representation of isothermal ion-ion-pair-solvent equilibria independent of
      changes in dielectric constant.

PMID- 16578678
TI  - Topological group structures of infinite symmetric groups.

PMID- 16578679
TI  - Pluricanonical systems on algebraic surfaces of general type.

PMID- 16578680
TI  - Nonlinear space-time transformations related to the lorentz group.

PMID- 16578682
TI  - The measurement of intercellular adhesion.

PMID- 16578681
TI  - PHAGE f2 RNA-DIRECTED BINDING OF FORMYLMETHIONYL-TRNA TO RIBOSOMES AND THE ROLE
      OF 30S RIBOSOMAL SUBUNITS IN INITIATION OF PROTEIN SYNTHESIS.

PMID- 16578683
TI  - ECDYSONE AND ECDYSONE ANALOGUES: THEIR ASSAY ON THE FLESHFLY Sarcophaga
      peregrina.

PMID- 16578684
TI  - The dirichlet problem for quasilinear equations with many independent variables.

PMID- 16578686
TI  - General principal forms imitating locally square integrable forms.

PMID- 16578685
TI  - Infinite games and analytic sets.

PMID- 16578687
TI  - On the number of multiplications required to compute certain functions.

PMID- 16578688
TI  - The elastic dielectric.

PMID- 16578689
TI  - A novel reaction of a nitro sugar with alcohols.

PMID- 16578690
TI  - Random evolutions, markov chains, and systems of partial differential equations.
AB  - Several authors have considered Markov processes defined by the motion of a
      particle on a fixed line with a random velocity(1, 6, 8, 10) or a random
      diffusivity.(5, 12) A "random evolution" is a natural but apparently new
      generalization of this notion. In this note we hope to show that this concept
      leads to simple and powerful applications of probabilistic tools to initial-value
      problems of both parabolic and hyperbolic type. We obtain existence theorems,
      representation theorems, and asymptotic formulas, both old and new.

PMID- 16578691
TI  - Fundamental domains for lattices in rank one semisimple lie groups.
AB  - We construct a fundamental domain omega for an arbitrary lattice [unk] in a real
      rank one, real simple Lie group, where omega has finitely many cusps (i.e., is a
      finite union of Siegel sets) and has the Siegel property (i.e., the set {gamma
      [unk] [unk]|omegagamma [unk] omega [unk] varphi} is finite). From the existence
      of omega we derive a number of consequences. In particular, we show that [unk] is
      finitely presentable and is almost always rigid.

PMID- 16578692
TI  - Riemannian manifolds admitting a conformal transformation group.
AB  - Let M be a Riemannian manifold with constant scalar curvature K which admits an
      infinitesimal conformal transformation. A necessary and sufficient condition in
      order that it be isometric with a sphere is obtained.Inequalities giving upper
      and lower bounds for K are also derived.

PMID- 16578693
TI  - Theta constants, moduli, and compact riemann surfaces.
AB  - One of the classical tools for the study of moduli of compact Riemann surfaces is
      the Riemann theta function. Preliminary results were announced earlier(1) which
      established relations between two kinds of theta constants on a compact Riemann
      surface of genus 2. In this note we generalize the results there obtained. The
      main theorem is as follows:A sufficient condition for [Formula: see text] to be
      independent of [Formula: see text] is that [Formula: see text] for the 2(g-2)(2(g
      1) - 1) characteristics [Formula: see text] where [Formula: see text] ranges over
      all odd g - 1 characteristics.

PMID- 16578694
TI  - On closed extensions of functions.
AB  - G. T. Whyburn has shown that every mapping (by a mapping we will always mean a
      continuous function) of a topological space into a Hausdorff space is the
      restriction of a compact mapping with the same range (Trans. Am. Math. Soc., 74,
      344-350 (1953)). H. Bauer has proved that every mapping between locally compact
      Hausdorff spaces can be extended in a topologically unique manner to a compact
      mapping on a locally compact Hausdorff space with the same range (Math. Ann.,
      138, 398-427 (1959)). When the range and domain of a mapping are locally compact
      Hausdorff spaces, Whyburn's and Bauer's extensions are topologically equivalent.
      It is well known that not every compact mapping is a closed mapping; however,
      Whyburn has shown that every closed function with compact point inverses is a
      compact function (these PROCEEDINGS, 54, 688-692 (1965)). The principal aim of
      this paper is to prove that every function (respectively, mapping) from one
      topological space to another can be extended in a topologically unique manner to
      a closed and compact function (respectively, mapping) with the same range.

PMID- 16578695
TI  - Some remarks about liquid metals.
AB  - This paper proposes that the liquid state in metals consists of clusters, or
      globs, of ordered material separated by very thin layers of defects. The nature
      of the defects surrounding each glob and separating it from neighboring globs is
      the main feature of the theory. The volume of each defect and the energy to
      produce it is found to be only a fraction of that required to produce an ordinary
      vacancy in a solid. A close correlation is shown to exist between this theory and
      Eyring's theory of significant structures.(1-7) The heats of fusion and the
      volume changes on melting can be computed, as can be the coordination numbers in
      the liquid state.

PMID- 16578696
TI  - Resonance stabilization of cycle groups of hydrogen-bonded water molecules.
AB  - A quantum-mechanical resonance effect can be associated with cyclic groups of
      hydrogen-bonded water molecules and, conceivably, might influence the structure
      of liquid water (M. Ageno, these PROCEEDINGS, 57, 567 (1967)). However, from the
      calculations presented here, this resonance stabilization appears to be too small
      (<0.1 kcal/mole) to over come the thermal motion of the water molecules and
      consequently cannot significantly influence the liquid water structure. The model
      developed here permits the estimation of an upper limit to the stabilization. The
      bridge protons are imagined to be simultaneously tunneling through the barriers
      of equivalent symmetric double-well potentials, and the resulting energy-level
      splittings are related to the resonance stabilization.

PMID- 16578697
TI  - Chairman'S introductory remarks.

PMID- 16578698
TI  - THE MANGANESE MERCURY STAR pi(1) BOOTIS.
AB  - High-dispersion plates secured with the Coude spectrograph of the Lick 120 inch
      telescope have been used to analyze the peculiar A star pi(1) Bootis. Spectral
      energy distribution measurements are combined with line-intensity data for iron
      and manganese in two stages of ionization to obtain a fit with model atmospheres
      for T(eff) = 13,000 degrees K and log g = 4. The influence of adopted T and g on
      the derived abundances is discussed. Although C, O, Mg, Si, Ti, Cr, and Fe appear
      to have nearly normal (i.e., solar) abundances, strontium appears to be enhanced
      in abundance by an order of magnitude, and scandium is about 50 times
      overabundant, while manganese and yttrium appear to be two orders of magnitude
      overabundant. If the identification of gallium is correct, this element is
      overabundant by a factor approaching 100,000; while if lambda3983.90 is to be
      attributed to HgII, as Bidelman suggests, the overabundance of this element is
      many orders of magnitude.

PMID- 16578699
TI  - Emission-line objects projected upon the galactic bulge.
AB  - Low-dispersion slit spectrograms have been obtained of 34 faint objects that lie
      in the direction of the galactic bulge and have the Halpha line in emission upon
      a detectable continuum. Eleven of these are certain or probable symbiotic stars.
      A rough comparison with R CrB stars in the same area suggests that these
      brightest symbiotics in the bulge have in the mean M(v) approximately -3 to -4,
      which suggest Population II red giants rather than conventional Population I M
      type objects. The sample also contains a number of hot stars having H and [O II]
      or [O III] in emission, as well as four conventional Be stars, and six certain or
      possible planetary nebulae.

PMID- 16578700
TI  - Homogeneous catalogs of earthquakes.
AB  - The usual bias in earthquake catalogs against shocks of small magnitudes can be
      removed by testing the randomness of the magnitudes of successive shocks. The
      southern California catalog, 1933-1967, is found to be unbiased in the sense of
      the test at magnitude 4 or above; the cutoff is improved to M = 3 for the
      subcatalog 1953-1967.

PMID- 16578701
TI  - On the motion of a sphere in a perfect fluid, with application to liquid helium.
AB  - Momentum relationships involved in the motion of a sphere through a perfect fluid
      are considered. The mechanism, by which the momentum given to a sphere by an
      external impulsive force is transferred to the container as a whole, is traced
      through in some detail, and energy and momentum relationships are discussed.
      Comparison is made with a (3)He atom or a roton moving in superfluid (4)He.

PMID- 16578702
TI  - Wilder manifolds are locally orientable.
AB  - A proof is given for the long-standing conjecture of R. L. Wilder that every
      generalized manifold is locally orientable. Roughly speaking, a generalized n
      manifold is a locally compact space whose local homology groups at each point are
      those of an n-manifold. Local orientability is a condition in which the local
      homology groups at neighboring points have a certain nice relationship to one
      another. Local orientability is indispensable for almost all applications.

PMID- 16578703
TI  - Conjugate points of second-order linear differential equations.
AB  - The paper of which the present article is itself an abstract is concerned with
      locating zeros of nonnull solutions of differential systems of the
      formcplx=fwhere r(x) and p(x) are continous and r(x) is positive for x >/= a.
      When r(x) = 1 and p(x) = alphax + beta, necessary conditions and sufficient
      conditions are pro-vided that the interval (a,b] contain n zeros. The results
      are, of course, of importanceconsiderably beyond the case when p(x) is linear.

PMID- 16578704
TI  - Toward a stochastic calculus, ii.
AB  - In a preceding note (these Proceedings, 63, 275 (1969)) singly and doubly
      stochastic integrals were defined. Here correspondingly generalized stochastic
      differential equations are studied. For constructing stochastic models of
      physical processes with random noises, by proper selection of the doubly
      stochastic terms, we remove the apparent discordances between classical and
      stochastic models.

PMID- 16578705
TI  - THE ACTION SPECTRUM FOR BREAKING DIAPAUSE IN THE CODLING MOTH, Laspeyresia
      pomonella (L.), AND THE OAK SILKWORM, Antheraea pernyi GUER.
AB  - The action spectrum for breaking diapause in the oak silkworm, Antheraea pernyi
      Guer., and the codling moth, Laspeyresia pomonella (L.), was determined from 400
      to 700 nm with a wedge-interference spectrograph. Insects were exposed to ten
      hours of white light, followed by six hours of spectral light each day for 45
      days. The portion of the spectrum between 400 and 500 nm was found to be the most
      effective in terminating diapause. Diapause was broken for both insects with
      energy levels as low as 0.02 muw/cm(2).

PMID- 16578706
TI  - Inference from Inadequate and Inaccurate Data, II.
AB  - Having measured D numerical properties of a physical object E which requires many
      more than D parameters for its complete specification, an observer seeks to
      estimate P other numerical properties of E. A previous paper discussed how he can
      proceed when E is adequately described by one member m(E) of a Hilbert space
      [unk] of possible models of E and when all the observed and sought-for properties
      of E are Frechet differentiable functionals on [unk]. The present paper describes
      a technique often available for reducing to this tractable case problems in which
      the functionals are discontinuous and are defined only on parts of [unk], and
      [unk] is an arbitrary real linear space. Applications include geophysical inverse
      problems and numerical differentiation, integration, interpolation, and
      extrapolation.

PMID- 16578707
TI  - Physical particle representation and generalized transformation theory.
AB  - The investigation of the recently described generalized transformation theory
      which leads to a non-Hamiltonian description of dynamics is pursued. The concept
      of generalized unitary transformations of superoperators is introduced and a
      specific class of transformations studied. For nondissipative systems it is
      equivalent to the usual unitary transformations that diagonalize the Hamiltonian.
      The important point is that this class of transformations remains meaningful for
      dissipative systems, hence a new representation of dynamics that we shall call
      the "physical particle" representation. It has the following properties: (a) The
      energy (or an arbitrary function of the energy) is represented by a diagonal
      matrix. (b) In the ((0))II space (see these Proceedings, 65, 789 (1970))
      corresponding to the coherent processes, the evolution can be described in terms
      of the changes in population of the physical particles. (c) At thermodynamic
      equilibrium, the physical particles are uncorrelated and behave as independent
      entities; the entropy has a purely combinatorial meaning.A full description of
      dynamics in this representation will be given in a forth-coming paper.

PMID- 16578708
TI  - A hummingbird-pollinated species of boraginaceae in the Arizona flora.
AB  - Marcomeria viridiflora (Boraginaceae) is pollinated by broad-tailed and rufous
      hummingbirds in the White Mountains of Arizona. This is the first hummingbird
      pollinated member of the family Boraginaceae to be recorded in western North
      America. It provides one more example of a predominantly beepollinated plant
      group that has given rise to one or a few exceptional species of hummingbird
      flowers in western North America.

PMID- 16578709
TI  - Solar abundance of gallium.
AB  - The spectral region around the lambda4172 A resonance line of gallium has been
      synthesized at disk positions mu = 1.0, 0.5, and 0.3. The center-limb variation
      can be reproduced by Elste's semiempirical model if a macroturbulent smearing of
      the emergent spectrum due to mass motions with mean velocity decreasing with
      altitude are introduced. The abundance of Ga derived from disk position mu = 1 is
      found to be log [N(Ga)/N(H)] + 12 = 2.80.

PMID- 16578710
TI  - The spectrum of seminormal operators.
AB  - With every pair of bounded self-adjoint operators {U,V} on Hilbert space such
      that VU - UV = (1/pii)C, where C is trace class, there is associated a certain
      function of two complex variables called the determining function of the pair. It
      was previously shown how the determining function can be obtained as the solution
      of a certain Riemann-Hilbert problem canonically associated with the pair, and
      how the complete spectral multiplicity theory for both U and V can be obtained
      from the determining function. We now show, under the condition that C is
      semidefinite, that the determining function method leads to a simple
      characterization of the spectrum of the seminormal operator T = U + iV.

PMID- 16578711
TI  - Systems of conservation equations with a convex extension.
AB  - We discuss first-order systems of nonlinear conservation laws which have as a
      consequence an additional conservation law. We show that if the additional
      conserved quantity is a convex function of the original ones, the original system
      can be put into symmetric hyperbolic form. Next we derive an entropy inequality,
      which has also been suggested by I. Kruzhkov, for discontinuous solutions of the
      given system of conservation laws.

PMID- 16578712
TI  - Alternative derivations of the statistical mechanical distribution laws.
AB  - A new approach is presented for the derivation of statistical mechanical
      distribution laws. The derivations are accomplished by minimizing the Helmholtz
      free energy under constant temperature and volume, instead of maximizing the
      entropy under constant energy and volume. An alternative method involves
      stipulating equality of chemical potential, or equality of activity, for
      particles in different energy levels. This approach leads to a general statement
      of distribution laws applicable to all systems for which thermodynamic
      probabilities can be written. The methods also avoid use of the calculus of
      variations, Lagrangian multipliers, and Stirling's approximation for the
      factorial. The results are applied specifically to Boltzmann, Fermi-Dirac, and
      Bose-Einstein statistics. The special significance of chemical potential and
      activity is discussed for microscopic systems.

PMID- 16578713
TI  - Rapid change in water flux induced by auxins.
AB  - Auxin (indole-3-acetic acid) enhances movement of tritiated water into and out of
      stem segments of etiolated peas. The time required for water in the tissue to
      attain one-half equilibrium with water in the surrounding solution is
      significantly shorter and the initial flux rate is higher in auxin-treated
      sections. The response is one of the most rapid to auxin, occurring well within 1
      min after application of the hormone. This suggests that an action of auxin on
      the membrane system occurs before or coincident with auxin-induced enhancement of
      growth and wall elastic extensibility.

PMID- 16578714
TI  - The "up-down" problem for operator algebras.
AB  - It is shown that for any C(*)-algebra A of operators on a separable Hilbert
      space, there is, for each self-adjoint operator x in the strong closure of A, a
      sequence {x(n)} of self-adjoint operators, each of which is the strong limit of a
      monotone increasing sequence of self-adjoint operators from A, such that {x(n)}
      is monotone decreasing and strongly convergent to x.

PMID- 16578715
TI  - Empirical correlation between hydrophobic free energy and aqueous cavity surface
      area.
AB  - The unitary free energy of transfer of a hydrocarbon molecule from a hydrocarbon
      solvent to an aqueous medium is a measure of the hydrophobic interaction in the
      aqueous medium. We have reexamined available data on this phenomenon and have
      confirmed that the free energy for saturated hydrocarbons is proportional to the
      surface area of the cavity created by the solute in the aqueous solution, with
      the same proportionality constant for linear, branched, and cyclic hydrocarbon
      molecules. The numerical value of the proportionality constant is uncertain
      because absolute and self-consistent area measurements are not available. We
      estimate that it falls between 20 and 25 cal/mole per A(2) at 25 degrees (for
      areas measured at the distance of closest approach of water molecules), which is
      significantly less than the figure of 33 cal/mole per A(2) that has been assigned
      to the same parameter by Hermann [J. Phys. Chem. 76, 2754-2759 (1972)]. A small
      discrepancy exists when similar data for homologous series of alkyl derivatives
      are compared with results based on hydrocarbons themselves, and possible reasons
      for it are discussed.

PMID- 16578716
TI  - Nuclear magnetic resonance spectroscopy. Ring-current effects on carbon-13
      chemical shifts.
AB  - A comparison of the (13)C nuclear magnetic resonance chemical shifts of some
      15,16-dialkyl-15,16-dihydropyrenes with the corresponding 15,16-dialkyl-2,7,15,16
      tetrahydropyrenes provides a measure of the effect of ring current on carbon-13
      chemical shifts in which other effects may be expected to be negligibly small.
      The general conclusion is that the absolute magnitude of the ring-current effect
      is the same for carbon-13 as for protons when they occupy the same position in
      space relative to the aromatic pi-electron cloud.

PMID- 16578717
TI  - Photon propagation function: spectral analysis of its asymptotic form.
AB  - The physical attitudes of source theory, displacing those of renormalized,
      perturbative, operator field theory, are used in a simple discussion of the
      asymptotic behavior of the photon propagation function. A guiding principle is
      the elementary consistency requirement that, under circumstances where a physical
      parameter cannot be accurately measured, no sensitivity to its precise value can
      enter the description of those circumstances. The mathematical tool is the
      spectral representation of the propagation function, supplemented by an
      equivalent phase representation. The Gell-Mann-Low equation is recovered, but
      with their function now interpreted physically as the spectral weight function. A
      crude inequality is established for the latter, which helps in interpolating
      between the initial rising behavior and the ultimate zero at infinite mass. There
      is a brief discussion of the aggressive source theory viewpoint that denies the
      existence of a "bare charge".

PMID- 16578718
TI  - Classical statistical mechanics of constraints: a theorem and application to
      polymers.
AB  - A classical system of mass points subject to holonomic constraints has a kinetic
      energy dependent on the coordinates as well as the moments of the remaining
      degrees of freedom. Coordinate averages formed in the reduced space of
      unconstrained coordinates and their conjugate momenta then involve a metric
      determinant that may be difficult to evaluate. A theorem is derived that permits
      a relatively easy evaluation when the constraints are distances between
      particles, and an application is made to a Kramers type freely jointed chain.

PMID- 16578719
TI  - The significant structure theory applied to amorphous and crystalline
      polyethylene.
AB  - The significant structure theory of liquids has been applied to amorphous and
      crystalline polyethylene. In this theory the amorphous state, like liquids in
      general, is assumed to have solid-like structure, gaslike structure, and
      positional degeneracy which arises from the motion of kinetic segments and from
      the libration of CH(2) units. This concept leads to a partition function giving
      the Helmholtz free energy in terms of volume, temperature, and
      composition.Thermodynamic and transport properties are calculated for amorphous
      polyethylene. The thermodynamic properties are also calculated for the
      crystalline solid. The calculated results are in reasonable agreement with the
      experimental values. No such detailed calculations of polymer properties from a
      partition function, depending on both volume and temperature, have been
      previously attempted.

PMID- 16578720
TI  - On the interpretation of experiments on osmotic pressure.
AB  - Scholander and his coworkers have described in These Proceedings several
      experiments in which the osmotic pressure exerted by colloidal particles appears
      to be altered when the particles are subject to an external force; they interpret
      the experiments as showing that the traditional explanation of osmotic pressure
      is wrong (Proc. Nat. Acad. Sci. USA 68, 1093-1094; 68, 1569-1571; 70, 124-128).
      (In their view the osmotic pressure is determined by the concentration of the
      colloidal particles at the free surface rather than at the semipermeable
      membrane.) This note shows that one must also consider the way in which the
      external force changes the total hydrostatic pressure in the liquid. When that is
      done, the experiments of Scholander et al. are quantitatively consistent with the
      traditional interpretation of osmotic pressure.

PMID- 16578721
TI  - On the use of mist nets for population studies of birds.
AB  - Studies in which birds are captured in mist nets, marked, and released can yield
      much more information than previously realized. When nets are erected, the
      capture rate is initially high and then decreases with time, as more and more of
      the resident bird individuals in the vicinity are captured and learn to avoid the
      nets a second time. The capture rate eventually reaches an asymptotic value
      depending on the number of "drifting," nonresident individuals in the vicinity.
      We describe a simple theoretical formulation of this decline in capture rate, and
      we show how it can be used to estimate the sizes of the resident population and
      the drifting population separately. To illustrate the theory, we apply it to the
      results of a netting study in a Vermont forest. Variation among species in
      capture efficiency is correlated in part with preferred vertical foraging
      position. Species may be characterized as "smart" or "dumb" by the criterion of
      relative recapture frequency.

PMID- 16578722
TI  - Home range orientation and territoriality in harvesting ants.
AB  - Trunk trails, used by Pogonomyrmex barbatus and P. rugosus during foraging and
      homing, have the effect of avoiding aggressive confrontations between neighboring
      colonies of the same species. They channel the mass of foragers of hostile
      neighboring nests into diverging directions, before each ant pursues its
      individual foraging exploration. This channeling subtly partitions the foraging
      grounds and allows a much denser nest spacing pattern than a foraging strategy
      without trunk trails, such as that employed by P. maricopa.

PMID- 16578723
TI  - Atomic regime in which the magnetic interaction dominates the coulomb interaction
      for highly excited States of hydrogen.
AB  - The atomic regime in which the interaction of the electron with an external
      magnetic field dominates the Coulomb interaction with the nucleus, relevant to
      pulsars, can be realized at laboratory magnetic fields for discrete autoionized
      states of hydrogen, at energies above the ionization limit. Approximate wave
      functions, energy levels, and electric dipole transition probabilities are
      presented for hydrogen, and an atomic beam absorption spectroscopy experiment at
      50 kG is proposed to study this new regime.

PMID- 16578724
TI  - Some distributions associated with bose-einstein statistics.
AB  - This paper examines a stochastic process for Bose-Einstein statistics that is
      based on Gibrat's Law (roughly: the probability of a new occurrence of an event
      is proportional to the number of times it has occurred previously). From the
      necessary conditions for the steady state of the process are derived, under two
      slightly different sets of boundary conditions, the geometric distribution and
      the Yule distribution, respectively. The latter derivation provides a simpler
      method than the one earlier proposed by Hill [J. Amer. Statist. Ass. (1974) 69,
      1017-1026] for obtaining the Pareto Law (a limiting case of the Yule
      distribution) from Bose-Einstein statistics. The stochastic process is applied to
      the phenomena of city sizes and growth.

PMID- 16578725
TI  - Fall-off from extrapolated values of all chemical reactions at very high
      temperatures.
AB  - At high temperatures the breaking of chemical bonds becomes relatively easy and
      the slow step in a chemical reaction shifts to the rate at which energy can seep
      into the bond that is to break. This has been observed by various investigators.
      A new general theory of reactions is developed here to explain this limiting rate
      at high temperatures. In the case of cyclopropane and cyclobutane the theory
      leads to the conclusion that 20 degrees of freedom form a heat reservoir which
      feeds the energy into the carbon bond that is to break and that this rate becomes
      controlling above about 1200 degrees K. This would correspond to 20 of the 21
      vibrational bonds of cyclopropane feeding energy into the carbon bond that is to
      break, and there would be no noticeable rise in the number of bonds for
      cyclobutane. This theory is especially important for shock tubes and detonations,
      where this falling-off from the extrapolated low temperature rate becomes
      glaringly obvious.

PMID- 16578726
TI  - Lagrange multiplier method for convex programs.
AB  - The problem of minimizing a convex function that is subject to the constraint
      that a number of other convex functions be nonpositive can be treated by the
      Lagrange multiplier method. Such a treatment was revived by Kuhn and Tucker and
      further studied by many other scientists. These studies led to an associated
      maximizing problem on the Lagrange function. The aim of this note is to give a
      short elementary proof that the infimum of the first problem is equal to the
      supremum of the second problem. To carry this out it is necessary to relax the
      constraints of the first (or the second) problem so that the constraints are
      enforced only in the limit. This relaxation of constraints is not necessary
      should prescribing upper bounds to all the convex functions define a bounded set
      of points in the domain of the functions. The domain of the functions can be n
      dimensional space or a reflexive Banach space.

PMID- 16578727
TI  - Strongly nonlinear integral equations of hammerstein type.
AB  - This paper studies the solution of the nonlinear Hammerstein equation u(x) +
      k(x,y)f[y,u(y)]mu(dy) = h(x) in the singular case, i.e., where the linear
      operator K with kernel k(x,y) is not defined for all the range of the nonlinear
      mapping F given by Fu(y) = f[y,u(y)] over the whole class X of functions u which
      are potential solutions of the equation. An existence theorem is derived under
      relatively minimal assumptions upon k and f, namely that (Ku,u) >/= 0, that K
      maps L(1) into L(1) (loc) and is compact from L(1) [unk] L(infinity) into L(1)
      (loc), that f(y,s) has the same sign as s for s >/= R, and that for each constant
      r > 0, f(y,s) </= g(r)(y) for s </= r where g is bounded and summable. The proof
      is obtained by combining a priori bounds, a truncation procedure, and a
      convergence argument using the Dunford-Pettis theorem.

PMID- 16578728
TI  - Kinetic theory of viscosity of compressed fluids.
AB  - THE VISCOSITY OF A COMPRESSED GAS IS A FUNCTION OF THREE VARIABLES: (1) the
      degree of crowding of the molecules; (2) their capacity, by reason of softness,
      flexibility, or rotational inertia, to absorb the vector momentum applied to
      cause flow; (3) the resistance to this vector momentum offered by the randomly
      oriented thermal momenta, which becomes significant when the liquid expands
      sufficiently to permit molecular mean free paths between binary collisions to be
      long enough for thermal momenta to acquire fractions of their thermal momentum in
      free space.The fluidity varphi of simple liquids obeys the linear equation varphi
      = B(V - V(0))/V(0) and its viscosity is, therefore, eta(a) = V(0)/B(V - V(0));
      this accounts for components 1 and 2. The contribution of random thermal momenta,
      3, obeys the equation, eta(b) = eta(0)(1 - V(t)/V). eta(0) is the viscosity of
      the dilute gas; V(t) is the molal volume at which the thermal contribution
      begins. The total momentum, eta = eta(a) + eta(b).Values of eta(0) vary linearly
      with T(1/2). Values of V(t) are related to heat capacities.

PMID- 16578729
TI  - Adiabatic evolution of plasma equilibrium.
AB  - A new theory of plasma equilibrium is introduced in which adiabatic constraints
      are specified. This leads to a mathematically nonstandard structure, as compared
      to the usual equilibrium theory, in which prescription of pressure and current
      profiles leads to an elliptic partial differential equation. Topologically
      complex configurations require further generalization of the concept of
      adiabaticity to allow irreversible mixing of plasma and magnetic flux among
      islands. Matching conditions across a boundary layer at the separatrix are
      obtained from appropriate conservation laws. Applications are made to
      configurations with planned islands (as in Doublet) and accidental islands (as in
      Tokamaks). Two-dimensional, axially symmetric, helically symmetric, and closed
      line equilibria are included.

PMID- 16578730
TI  - Maximum-valence radii of transition metals.
AB  - In many of their compounds the transition metals have covalence 9, forming nine
      bonds with use of nine hybrid spd bond orbitals. A set of maximum-valence single
      bond radii is formulated for use in these compounds. These radii are in
      reasonably good agreement with observed bond lengths. Quadruple bonds between two
      transition metal atoms are about 50 pm (iron-group atoms) or 55 pm (palladium and
      platinum-group atoms) shorter than single bonds. This amount of shortening
      corresponds to four bent single bonds with the best set of bond angles, 79.24
      degrees and 128.8 degrees .

PMID- 16578731
TI  - Point estimates for probability moments.
AB  - Given a well-behaved real function Y of a real random variable X and the first
      two or three moments of X, expressions are derived for the moments of Y as linear
      combinations of powers of the point estimates y(x(+)) and y(x(-)), where x(+) and
      x(-) are specific values of X. Higher-order approximations and approximations for
      discontinuous Y using more point estimates are also given. Second-moment
      approximations are generalized to the case when Y is a function of several
      variables.

PMID- 16578732
TI  - General almost automorphy.
AB  - We will propose a very general setting for the following proposition. If a linear
      operator Lf is almost automorphic and all bounded solutions of the homogeneous
      equation Lg = 0 are almost automorphic then, for almost automorphic phi, all
      bounded solutions of the inhomogeneous equation Lf = phi are also almost
      automorphic.The almost automorphy previously introduced by us will be generalized
      and diversified into a property which we will name "A-invariance"; and we will
      deal with both strong solutions and weak solutions. We will also compare our A
      invariance with minimality, and propose a rather thinned-out almost periodicity
      that will be associated with our A-invariance.

PMID- 16578733
TI  - Partial knowledge, entropy, and estimation.
AB  - In a growing body of literature, available partial knowledge is used to estimate
      the prior probability distribution p identical with(p(1),...,p(n)) by maximizing
      entropy H(p) identical with-Sigmap(i) log p(i), subject to constraints on p which
      express that partial knowledge. The method has been applied to distributions of
      income, of traffic, of stock-price changes, and of types of brand-article
      purchases. We shall respond to two justifications given for the method:(alpha) It
      is "conservative," and therefore good, to maximize "uncertainty," as (uniquely)
      represented by the entropy parameter.(beta) One should apply the mathematics of
      statistical thermodynamics, which implies that the most probable distribution has
      highest entropy.Reason (alpha) is rejected. Reason (beta) is valid when "complete
      ignorance" is defined in a particular way and both the constraint and the
      estimator's loss function are of certain kinds.

PMID- 16578734
TI  - Stochastic models for the Earth's relief, the shape and the fractal dimension of
      the coastlines, and the number-area rule for islands.
AB  - The degree of irregularity in oceanic coastlines and in vertical sections of the
      Earth, the distribution of the numbers of islands according to area, and the
      commonality of global shape between continents and islands, all suggest that the
      Earth's surface is statistically self-similar. The preferred parameter, one which
      increases with the degree of irregularity, is the fractal dimension, D, of the
      coastline; it is a fraction between 1 (limit of a smooth curve) and 2 (limit of a
      plane-filling curve). A rough Poisson-Brown stochastic model gives a good first
      approximation account of the relief, by assuming it to be created by superposing
      very many, very small cliffs, placed along straight faults and statistically
      independent. However, the relative area predicted for the largest islands is too
      small, and the irregularity predicted for the relief is excessive for most
      applications; so is indeed the value of the dimension, which is D = 1.5. Several
      higher approximation self-similar models are described. Any can be matched to the
      empirically observed D, and can link all the observations together, but the
      required self-similarity cannot yet be fully explained.

PMID- 16578735
TI  - Solar abundance of iridium.
AB  - By a method of spectrum synthesis, which yields log gfA, where g is the
      statistical weight of the lower level, f is the oscillator strength, and A is the
      abundance, an attempt is made to deduce the solar iridium abundance from one
      relatively unblended, but fairly weak IrI line, lambda 3220.78 A. If the Corliss
      Bozman f-value for this line is adopted, we find log A(Ir) = 0.82 on the scale
      log A(H) = 12.00. The discordance with the value found from carbonaceous
      chondrites may arise from faulty f-values or from difficulties arising from line
      blending in this far ultraviolet domain of the solar spectrum.

PMID- 16578736
TI  - Correlation of nonorthogonality of best hybrid bond orbitals with bond strength
      of orthogonal orbitals.
AB  - An expression is derived for the bond length of two spd orbitals with maximum
      values in two directions forming a given bond angle by consideration of the
      nonorthogonality integral of two best orbitals in these directions. This equation
      is equivalent to the expression derived by formulating the pair of orthogonal
      orbitals. Similar expressions are derived for spdf orbitals. Applications are
      made to icosahedral and cuboctahedral bonds and to the packing of nucleons in
      atomic nuclei.

PMID- 16578737
TI  - Delayed singularity formation for solutions of nonlinear partial differential
      equations in higher dimensions.
AB  - Strict solutions u of genuinely nonlinear homogeneous hyperbolic equations in two
      independent variables with initial data f(x) of compact support become singular
      after a time interval of order parallelf parallel(-1). In higher dimensions
      solutions initially of compact support are likely to have life expectancies of
      orders parallelf parallel(-2+epsilon) at least. This is proved for the special
      case of solutions u(x(1),..., x(n), t) of a second order equation u(tt) =
      Sigma(i,j)a(ij)u(xixj), where n >/= 3 and where the coefficients a(ij) are
      C(infinity)-functions in the first derivatives of u, forming a symmetric positive
      definite matrix.

PMID- 16578738
TI  - On the lifetime-width relation for a decaying state and the uncertainty
      principle.
AB  - A new formulation of the uncertainty relation of position and momentum, and of
      energy and time, is presented. The connection between the lifetime of excited
      states and the energy width of these states, which does not follow from the usual
      uncertainty relation, is shown to be a consequence of the expression here
      derived.

PMID- 16578739
TI  - Maximally dependent random variables.
AB  - Let X(1),..., X(n) have an arbitrary common marginal distribution function F, and
      let M(n) = max(X(1),..., X(n)). It is shown that EM(n) </= m(n), where m(n) =
      a(n) + n[unk](an) (infinity)[1 -F(x)]dx and = F(-1)(1 - n(-1)), and that EM(n) =
      m(n) when X(1),..., X(n) are "maximally dependent"; i.e., P(M(n) > x) = min{1,
      n[1 - F(x)]} for all x. Moreover, as n --> infinity, a(n) approximately m(n)
      approximately m(n) (*), where m(n) (*) = EM(n) when X(1),..., X(n) are
      independent, provided that [1 - F(cx)]/[1 - F(x)] --> 0 as x --> infinity for
      every c > 1, and E(X(1) (-))(r) < infinity for some r > 0. The case in which F is
      standard normal is considered in detail.

PMID- 16578740
TI  - Biliproteins of cyanobacteria and Rhodophyta: Homologous family of photosynthetic
      accessory pigments.
AB  - Amino-terminal sequence determinations are reported of the subunits of
      biliproteins of prokaryotic unicellular and filamentous cyanobacteria and of
      eukaryotic unicellular red algae. The biliproteins examined, allophycocyanin, C
      phycocyanin, R-phycocyanin, b-phycoerythrin, and phycoerythrocyanin, vary with
      respect to the chemical nature and the number and distribution of the bilin
      chromophores between the two dissimilar subunits. The amino-terminal sequences
      fall into two classes, "alpha-type" and "beta-type", with a high degree of
      homology within each class.In those biliproteins where the number of bilin
      chromophores on the two subunits is unequal, the subunit with the greater number
      of chromophores has the beta-type amino-acid sequence.Extensive homology also
      exists between alpha- and beta-type sequences, strongly supporting the view that
      these arose by gene duplication to give rise to the ancestral alpha- and beta
      type genes early in the evolution of the biliproteins. The subsequent generation
      of the various classes of biliproteins appears to be the result of further gene
      duplication of the alpha- and beta-type genes, ultimately to give rise to
      families of polypeptide chains of similar sequence, but varying in the number of
      chromophore attachment sites and the structure of the chromophores.

PMID- 16578741
TI  - Polypeptide splicing.

PMID- 16578742
TI  - Evolution, population dynamics, and stability.
AB  - By treating mutant populations as fluctuations relating to the structural
      stability of the equations of population dynamics, a criterion is developed
      permitting the prediction of long-term population trends in an evolving eco
      system. As an illustration it is shown that the ratio of predator to prey biomass
      increases under the effects of their combined evolution.

PMID- 16578743
TI  - Theoretical foundations of the chronometric cosmology.
AB  - The derivation of the redshift (z)-distance (r) relation in the chronometric
      theory of the Cosmos is amplified. The basic physical quantities are represented
      by precisely defined self-adjoint operators in global Hilbert spaces.
      Computations yielding explicit bounds for the deviation of the theoretical
      prediction from the relation z = tan(2)(r/2R) (where R denotes the radius of the
      universe), earlier derived employing less formal procedures, are carried out for:
      (a) a cut-off plane wave in two dimensions; (b) a scalar spherical wave in four
      dimensions; (c) the same as (b) with appropriate incorporation of the photon
      spin. Both this deviation and the (quantum) dispersion in redshift are shown to
      be unobservably small. A parallel classical treatment is possible and leads to
      similar results.

PMID- 16578744
TI  - House monotone apportionment schemes.
AB  - AN EMPIRICAL COMPARISON IS GIVEN OF TWO SCHEMES OF CONGRESSIONAL APPORTIONMENT:
      Huntington's generally accepted Equal Proportion scheme, and a new "house
      monotone" Quota scheme. Evidence is given to show that Quota tends to
      underrepresent small states.

PMID- 16578745
TI  - A relativistic spherical vortex.
AB  - This investigation is concerned with stationary relativistic flows of an inviscid
      and incompressible fluid. In choosing a density-pressure relation to represent
      relativistic "incompressibility," it is found that a fluid in which the velocity
      of sound equals the velocity of light is to be preferred for reasons of
      mathematical simplicity. In the case of axially symmetric flows, the velocity
      field can be derived from a stream function obeying a partial differential
      equation which is nonlinear. A transformation of variables is found which makes
      the relativistic differential equation linear. An exact solution is obtained for
      the case of a vortex confined to a stationary sphere. One can make all three of
      the components of velocity vanish on the surface of the sphere, as in the
      nonrelativistic Hicks spherical vortex. In the case of an isolated vortex on
      whose surface the pressure is made to vanish, it is found that the pressure at
      the center of the sphere becomes negative, as in the nonrelativistic case.A
      solution is also obtained for a relativistic vortex advancing in a fluid. The
      sphere is distorted into an oblate spheroid. The maximum possible velocity of
      advance of the vortex is (2/3) c.

PMID- 16578747
TI  - Radiationless relaxation in "large" molecules: Experimental evidence for
      preparation of true molecular eigenstates and Born-Oppenheimer states by a
      coherent light source.
AB  - Photon absorption and emission by molecules that undergo radiationless
      transitions are examined using the single modes of lasers having well-defined
      coherence properties. Contrary to the usual beliefs, where it is assumed that the
      molecule is prepared in a Born-Oppenheimer singlet state and then "crosses-over"
      to other states (vibrationally "hot" singlets and/or triplets), it is shown
      experimentally that the true eigenstates of the molecule can be prepared, even in
      "large" molecules, if the laser correlation time is relatively long and the
      molecular relaxation is made slow. On the other hand, lasers with short (psec)
      correlation time have yielded effectively the singlet Born-Oppenheimer state,
      which has a much shorter lifetime than the true eigenstates. Effects of magnetic
      fields and temperature are also reported. The former changes the amount of mixing
      amongst the Born-Oppenheimer states. The latter, on the other hand, swings the
      molecule from being "small" (i.e., sparse vibronic structure with long lifetimes)
      to being "large" (i.e., dense statistical distribution of levels) since the
      relaxation between levels is very effective at high temperatures. Finally, the
      results of this work show that the words fluorescence and phosphorescence in
      their strict meaning are misleading if the true eigenstates, which may contain
      both singlet and triplet character, are prepared.

PMID- 16578746
TI  - Peroxidase complex with concomitant anodal and cathodal variation in red-fruited
      tomato species.
AB  - Four groups of bands (a-d) are controlled by 19 alleles of the Peroxidase-4 (Prx
      4) complex in the red-fruited tomato species, Lycopersicon esculentum and L.
      pimpinellifolium. Heterozygotes can be detected by virtue of codominance in all
      combinations except a few in which bands of single groups are absent ("semi-null"
      alleles). No recombinations were detected in 7419 F(2) segregants of 53 different
      combinations of alleles. A maximum fiducial limit (P = 0.01) of 0.08% crossing
      over between any Prx-4 band groups is estimated. Variation of the anodal b bands
      is absolutely associated with that of the cathodal d band in respect to presence
      versus absence and direction of migration. In respect to the origin of these
      variants, the probability of 18 instances of simultaneous mutation of genes at
      two loci, always in such complete agreement, is so remote that no more than one
      locus could conceivably govern b and d. The disposition of a is not similarly
      associated with that of the other bands, while that of the faint-staining c could
      not always be reliably resolved. The negation of all save extremely low
      recombination rates and the observed concomitant variation of b and d strongly
      support the concept of single locus control of all Prx-4 banding, this hypothesis
      being espoused until rejection should be required be required by future research.
      Models of single locus control of several isozymes are discussed.

PMID- 16578748
TI  - Cauchy integrals on Lipschitz curves and related operators.
AB  - In this note, we establish certain properties of the Cauchy integral on Lipschitz
      curves and prove the L(p)-boundedness of some related operators. In particular,
      we obtain the recent results of R. R. Coifman and Y. Meyer [(1976) "Commutateurs
      d'integrales singulieres:" Analyse harmonique d'Orsay n(o) 211, Universite Paris
      XI] on the continuity of the so-called commutator operators.

PMID- 16578749
TI  - Fourier analysis on the Heisenberg group.
AB  - We obtain a usable characterization of the (group) Fourier transform of (H(n))
      (Schwartz space on the Heisenberg group). The characterization involves writing
      elements of [Formula: see text] as asymptotic series in Planck's constant. In the
      process, we derive a new "discrete" version of spherical harmonics, and elucidate
      the theory of group contractions. We give an application to Hardy space theory.

PMID- 16578750
TI  - Theorems of Barth-Lefschetz type for complex subspaces of homogeneous complex
      manifolds.
AB  - Barth, Larsen, and others showed that complex submanifolds of complex projective
      space, CP(N), of small codimension strongly resemble CP(N) both homotopically and
      cohomologically. These results are generalized to yield analogous results for
      complex subspaces of arbitrary homogeneous complex manifolds. One very special
      corollary that gives the flavor of the results is:Corollary. Let A and B be
      complex submanifolds with B a connected submanifold of X, a simple Abelian
      variety, i.e., X has no proper sub-Abelian varieties. Then: [Formula: see text],
      where basepoints are suppressed for simplicity, and [Formula: see text]. Further,
      given any coherent sheaf on B, which may be assumed to be a connected local
      complete intersection, then: [Formula: see text] and given a coherent sheaf on X,
      then: [Formula: see text].

PMID- 16578751
TI  - High superconducting transition temperatures of new rare earth ternary borides.
AB  - A new group of ternary borides has been found that show either ferromagnetism or
      superconductivity. Their general formula is MRh(4)B(4) where M is a transition or
      rare-earth element. Their superconducting transition temperatures range from
      approximately 2.5 K for the Sm compound to approximately 12 K for the Lu
      compound.

PMID- 16578752
TI  - Crystallography of new ternary borides.
AB  - The structure of new ternary rhodium borides has been determined. Isomorphism
      with the corresponding ternary cobalt borides is established.

PMID- 16578753
TI  - Probabilistic theory of the three-phase structure seminvariant in the space group
      P1.
AB  - By embedding the three-phase structure seminvariant T and its symmetry-related
      variants in suitable quintets Q, one obtains the extensions Q of the seminvariant
      T. Because of the space group-dependent relationships among the phases, T is
      simply related to its extensions Q. In this way the probabilistic theory of the
      seminvariant T is reduced to that of the quintets Q, which is well developed. In
      particular, the neighborhoods of T are defined in terms of the neighborhoods of
      the Qs. The conditional probability distribution of the structure seminvariant T,
      given the seven magnitudes in its first neighborhood, is described for the space
      group P1. The distribution yields a reliable estimate (0 or pi) for T in the
      favorable case that the variance of the distribution happens to be small.

PMID- 16578754
TI  - Reliable ab initio calculation of a chemical reaction rate and a kinetic isotope
      effect: H + H(2) and H + H(2).
AB  - We calculate equilibrium rate constants for ortho-para conversion in hydrogen and
      deuterium by an atomic mechanism. The calculations are based on an accurate ab
      initio potential surface, transition state theory, and an adiabatic transmission
      coefficient. The calculated rate constants are demonstrated to be reliable within
      40-50%, and they agree with experiment within this margin.

PMID- 16578755
TI  - Float trajectories in simple kinematic flows.
AB  - A simple kinematic model has been used to compute Lagrangian trajectories.
      Although it is certainly too simple to model geophysical flows, it has provided
      insights into the behavior of Lagrangian tracers. In particular, the existence of
      trapping regions has been shown to greatly increase the dispersion rate of
      tracers and to lead to net tracer displacements when the Eulerian mean flow is
      zero. In general, the spectrum of spatial scales present in the trajectories is
      wider than the Eulerian spectrum and is biased towards shorter wavelengths; the
      disparity between the 100-km Eulerian scale and the much shorter length scales
      experienced by the tracers is demonstrated. The estimation of the Eulerian
      parameters of the field from Lagranian observations must be done with a great
      deal of care, particularly if the eddy flow velocities are comparable to or
      exceed the mean flow. With a limited number of tracers it is extremely difficult
      to estimate, with any degree of confidence, the properties of either the mean
      Eulerian flow or the eddy field. Clearly, more effort must be spent to better
      understand the behavior of tracers in more realistic flows, to devise data
      analysis techniques, and to relate the Eulerian and Lagrangian spectra.

PMID- 16578756
TI  - The boundary value problem for maximal hypersurfaces.
AB  - A spacelike hypersurface (condimension 1) in a Lorentzian manifold is called a
      maximal surface if it extremizes the hypervolume functional. Although maximal
      surfaces are superficially analogous to minimal hypersurfaces in Riemannian
      geometry, their properties can be dramatically different, as can be seen from the
      validity of Bernstein's theorem in all dimensions [Cheng, S.-Y. & Yau, S.-T.
      (1976) Ann. Math. 104, 407-419]. Here we establish a point of contact between
      maximal surfaces and minimal surfaces by solving the Dirichlet problem for
      acausal boundary data but using boundary curvature conditions similar to those of
      H. Jenkins and J. Serrin [(1968) J. Reine Angew. Math. 229, 170-187].

PMID- 16578757
TI  - Lyapounov variable: Entropy and measurement in quantum mechanics.
AB  - We discuss the question of the dynamical meaning of the second law of
      thermodynamics in the framework of quantum mechanics. Previous discussion of the
      problem in the framework of classical dynamics has shown that the second law can
      be given a dynamical meaning in terms of the existence of so-called Lyapounov
      variables-i.e., dynamical variables varying monotonically in time without
      becoming contradictory. It has been found that such variables can exist in an
      extended framework of classical dynamics, provided that the dynamical motion is
      suitably unstable. In this paper we begin to extend these results to quantum
      mechanics. It is found that no dynamical variable with the characteristic
      properties of nonequilibrium entropy can be defined in the standard formulation
      of quantum mechanics. However, if the Hamiltonian has certain well-defined
      spectral properties, such variables can be defined but only as a nonfactorizable
      superoperator. Necessary nonfactorizability of such entropy operators M has the
      consequence that they cannot preserve the class of pure states. Physically, this
      means that the distinguishability between pure states and corresponding mixtures
      must be lost in the case of a quantal system for which the algebra of observables
      can be extended to include a new dynamical variable representing nonequilibrium
      entropy. We discuss how this result leads to a solution of the quantum
      measurement problem. It is also found that the question of existence of entropy
      of superoperators M is closely linked to the problem of defining an operator of
      time in quantum mechanics.

PMID- 16578758
TI  - In vitro activation of insect prothoracic glands by the prothoracicotropic
      hormone.
AB  - An in vitro assay for the prothoracicotropic hormone has been developed that
      utilizes an ecdysone radioimmunoassay to quantify the increase in the rate of
      ecdysone synthesis elicited by the neurohormonal activation of the prothoracic
      glands. The rapidity, reproducibility, and accuracy of the assay were maximized
      by using one member of a gland pair as the control and the other as the test
      gland. This was possible because the basal rates of ecdysone synthesis by the
      members of a gland pair were equivalent. Activation was demonstrated to be dose
      dependent and specific, with prothoracicotropic hormone activity present only in
      homogenates of brain. The in vitro activation of the prothoracic glands was
      verified with the Manduca bioassay for the prothoracicotropic hormone in which
      the morphological responses to the hormone were correlated with increased in vivo
      ecdysone titers. These results provide unequivocal evidence that the activation
      of the prothoracic glands by the prothoracicotropic hormone is direct and suggest
      that activation represents an increase in a basal rate of ecdysone synthesis.

PMID- 16578759
TI  - In vitro binding of gibberellin A(4) to extracts of cucumber measured by using
      DEAE-cellulose filters.
AB  - A rapid method for assaying [(3)H]gibberellin A(4) bound to a soluble protein
      from cucumber hypocotyls by using DEAE-cellulose filter discs is described. The
      binding is saturable, reversible with unlabeled gibberellin A(4), and has a half
      life of association under nonequilibrium conditions at 0-4 degrees C of 6-7 min.
      By using this assay, the dissociation constant (K(d)) was estimated to be 70 nM
      and the number of binding sites, 0.4 pmol mg(-1) of soluble protein or 0.69 pmol
      g(-1) (fresh weight) of hypocotyls. The speed and reliability of the assay make
      it invaluable for kinetic studies involving competitors. Thus, it has been
      possible to show that gibberellins that are biologically active in a cucumber
      bioassay compete for binding to the same protein and their calculated affinity
      constants bear a direct relationship to their known activities in the cucumber
      bioassay. Gibberellins that are inactive in this bioassay and other plant
      hormones, such as indoleacetic acid, abscisic acid, and kinetin, show a
      noncompetitive interaction.

PMID- 16578760
TI  - Trophic and size structure of West Indian bird communities.
AB  - Much discussion has occurred in recent years on whether observed patterns of
      structure in island bird communities are the result of competitive interactions
      among species or independent rates of colonization and extinction. Here two
      patterns of structure are presented for birds on 12 West Indian islands. Each of
      four major foraging guilds shows a distinct species-area pattern on the islands
      and saturation of species within habitats on larger islands. Frugivores have the
      steepest species-area curve and highest species numbers at saturation while
      nectarivores are lowest in both values. Coexisting guild members in saturated
      habitats are generally of different sizes, with weight differences by a factor of
      2 common. On smaller islands, small guild members are absent and size differences
      among coexisting guild members may increase. In many cases, birds have apparently
      shifted size to conform to the structural patterns. The consistency of the
      patterns and variation within component species is highly compatible to
      explanations invoking competition and complements previously described population
      and community characteristics of West Indian birds.

PMID- 16578761
TI  - Perturbation and change in coral reef communities.
AB  - Ninety-six percent of surveyed shallow-water Dry Tortugas reef corals died during
      the severe winter of 1976-1977. Data from skeletal stains indicate that death
      occurred during the mid-January intrusion of 14 degrees C water onto the reef. In
      deeper water, community parameters such as percent cover, species number, and
      relative abundance showed no significant change. However, an analysis of
      competitive interactions at the growing edges of adjacent colonies reveals a 70%
      reduction in space competition during this environmental disturbance. These
      results can explain high variability in the growth rate of Floridian reefs and
      demonstrate the importance of obtaining long-term spatial information to
      interpret successional dynamics of complex communities.

PMID- 16578762
TI  - Effect of species pool size on species occurrence frequencies: Musical chairs on
      islands.
AB  - If species interactions affect species distributions, then species occurrence
      frequencies (nu(i)), defined as the fraction of an archipelago's islands that
      species i inhabits, should vary with species pool size. A "natural experiment"
      approximating this test is provided by the Bismarck, Solomon, and New Hebrides
      archipelagoes, whose bird species pools decrease in that order, the species of
      each archipelago being mostly a subset of those of the next richer archipelago.
      The average nu for an archipelago's species decreases with archipelago pool size.
      In the archipelago with the largest pool, most species are on few islands and few
      species are on most islands, whereas the reverse is true in the archipelago with
      the smallest pool. For species shared between two or more archipelagoes, nu(i)
      decreases with pool size or number of species in the same guild. These
      interarchipelagal differences in nu(i) or average nu reflect differences in level
      of interspecific competition, which reduces nus in species-rich archipelagoes in
      two ways: usually, by reducing a species' incidence on small islands and
      restricting the species to larger islands; less often (for so-called
      supertramps), by restricting a species to small islands.

PMID- 16578763
TI  - Evolution of interference competition by individual, family, and group selection.
AB  - The necessary conditions for the evolution of social behaviors in a population
      with three levels of biological organization are derived by using a population
      genetic model (one locus, two alleles, random mating, discrete generations).
      Total selection on the behavior, Deltaq, is partitioned into the sum of three
      components: (i) Deltaq(I), selection between individuals within families; (ii)
      Deltaq(F), selection between families within groups; and (iii) Deltaq(G),
      selection between groups of families. I show that any level of selection can be
      made to operate in concert with or in opposition to any other, depending upon the
      fitness effects of the behavior. The implications of the model are discussed in
      relation to those adaptive explanations of phenotypic traits that generally
      consider selection to operate only between individuals.

PMID- 16578764
TI  - Anisotropic magnetic interactions in the primary radical ion-pair of
      photosynthetic reaction centers.
AB  - The quantum yield of triplets formed by ion-pair recombination in quinone
      depleted photosynthetic reaction centers is found to depend on their orientation
      in a magnetic field. This new effect is expected to be a general property of
      radical pair reactions in the solid state. For 0 < H < 1,000 G, the quantum yield
      anisotropy is caused by anisotropic electron dipole-electron dipole or nuclear
      hyperfine interactions, or both. For high fields it is dominated by the
      anisotropy of the difference g-tensor in the radical ion-pair. The magnitude and
      sign of the contribution of each interaction depend not only on the values of the
      principal components of each anisotropic tensor but also on the geometric
      relationship of the principal axes of each tensor to the transition dipole moment
      used to detect the yield. A detailed formalism is presented relating these
      quantities to the observed yield anisotropy. The expected magnitude of each
      anisotropic parameter is discussed. It is demonstrated that the field dependence
      of the yield anisotropy is consistent with these values for certain reaction
      center geometries.

PMID- 16578765
TI  - Procedure for rapid isolation of photosynthetic reaction centers using cytochrome
      c affinity chromatography.
AB  - Horse heart cytochrome c linked to Sepharose 4B is used to purify reaction
      centers from Rhodopseudomonas sphaeroides R-26. This procedure allows for an
      initial recovery of 80-90% of the bacterial reaction centers present in
      chromatophore membranes. High purity reaction centers (A(280)/A(802) < 1.30) can
      be obtained with a 30% recovery. Reaction centers from wild-type Rps. sphaeroides
      and Rps. capsulata also bind to a cytochrome c column. Cytochrome c affinity
      chromatography can also be used to isolate photosystem I complexes from spinach
      chloroplasts.

PMID- 16578766
TI  - Localization of different photosystems in separate regions of chloroplast
      membranes.
AB  - The stoichiometric amounts and the photoactivity kinetics of photosystem I (PSI)
      and of the alpha and beta components of photosystem II (PSII(alpha) and
      PSII(beta)) were compared in spinach chloroplast membrane (thylakoid) fractions
      derived from appressed and nonappressed regions. Stroma-exposed thylakoid
      fractions from the nonappressed regions were isolated by differential
      centrifugation following a mechanical press treatment of the chloroplasts.
      Thylakoid vesicles derived mainly from the appressed membranes of grana were
      isolated by the aqueous polymer two-phase partition method. Stroma-exposed
      thylakoids were found to have a chlorophyll a/chlorophyll b ratio of 6.0 and a
      PSII(beta)/PSI reaction center ratio of 0.3. Kinetic analysis of system II
      photoactivity revealed the absence of PSII(alpha) from stroma-exposed thylakoids.
      The photoactivity of system I in stroma-exposed thylakoids showed a single
      kinetic component identical to that of unfractionated chloroplasts, suggesting
      that PSI does not receive excitation energy from the PSII-chlorophyll ab light
      harvesting complex. Thus, stroma-exposed thylakoids are significantly enriched in
      both PSI and PSII(beta). Inside-out vesicles from the appressed membranes of
      grana-partition regions had a chlorophyll a/chlorophyll b ratio of 2.0 and a
      PSII/PSI reaction center ratio of 10.0. The photoactivity of system II showed the
      membranes of the grana-partition regions to be significantly enriched in
      PSII(alpha). We conclude that PSII(alpha) is exclusively located in the membranes
      of the grana partitions while PSII(beta) and PSI are located in stroma-exposed
      thylakoids. The low PSI reaction center (P700) content of vesicles derived from
      grana partitions and the kinetic homogeneity of the PSI complex suggest total
      exclusion of P700 as a functional component in the membrane of the grana
      partition region.

PMID- 16578767
TI  - Grass leaf silicification: Natural selection for an inducible defense against
      herbivores.
AB  - Plants from four populations of three species of African grasses were collected
      from grasslands in Tanzania's Serengeti National Park that differ in the grazing
      intensity that they experience. Plants were grown in the laboratory in a
      factorial experiment in which variables were plant origin, species identification
      of plants, defoliation intensity, and supply of soluble silicate in the nutrient
      medium. All plants accumulated silica in leaf blades in the absence of soluble
      silicate from the nutrient medium. Plants native to the more heavily grazed
      grassland accumulated more silica in their leaf blades than did plants from the
      less heavily grazed site. Blade silica content was higher when plants were
      defoliated, indicating that silicification is an inducible defense against
      herbivores. The quantitative heterogeneity of this qualitatively homogeneous
      plant defense system may have contributed to the evolution of high species
      diversity in the grazing fauna.

PMID- 16578768
TI  - Long-wavelength-absorbing forms of bacteriochlorophyll a in solutions of Triton X
      100.
AB  - At least three forms of Triton X-100-solubilized bacteriochlorophyll a (BChl a)
      have been characterized by UV/visible/near-IR absorption and CD spectra. One,
      absorbing at 770 nm, is similar to a monomeric solution in methanol. The two
      others have strongly red-shifted absorption peaks (860 nm and 930, 835 nm) and
      intense and complex CD bands in this region, indicative of strong interaction of
      at least two and three molecules of BChl a, respectively.

PMID- 16578769
TI  - Autoregulatory control of translatable phytochrome mRNA levels.
AB  - Translatable phytochrome mRNA represents approximately 5 x 10(-3)% of the total
      poly(A)-RNA present in etiolated Avena seedlings, as determined by incorporation
      of radioactivity into the immunoprecipitable apoprotein in a cell-free
      translation system. Irradiation of such seedlings with 5-s red light induces a
      decline in this mRNA that is detectable within 15-30 min, shows a 50% reduction
      within 50-60 min, and results in a >95% reduction within 2 hr. The effect of the
      red light pulse is reversed by an immediately subsequent far-red pulse to the
      level of the far-red-light control, indicating that phytochrome exerts
      autoregulatory control over its own translatable mRNA level. This result
      necessitates revision of existing concepts of how phytochrome concentrations are
      modulated in vivo. Red-light dose-response curves show that the response is
      sensitive to very low light levels. Conversion of <1% of the total cellular
      phytochrome to the biologically active far-red-absorbing form is sufficient to
      induce approximately 60% of the maximal response, and 20% far-red-absorbing form
      saturates the response. The observed change in translatable phytochrome mRNA
      level is one of the most rapid phytochrome-induced alterations in any cellular
      mRNA yet recorded. Thus, autoregulation of phytochrome mRNA provides an
      attractive opportunity to examine the early sequence of events in phytochrome
      control of gene expression.

PMID- 16578771
TI  - Degree of mapping for nonlinear mappings of monotone type: Densely defined
      mapping.
AB  - The classical degree function constructed earlier for pseudomonotone mappings has
      been used to develop a broader degree theory of classical type for the sum of a
      maximal monotone map from a reflexive Banach space to its dual together with a
      bounded pseudomonotone map. The proof uses the generalized Yosida approximation
      of the maximal monotone mapping.

PMID- 16578772
TI  - Degree of mapping for nonlinear mappings of monotone type: Strongly nonlinear
      mapping.
AB  - The classical degree function developed earlier for pseudomonotone operators from
      a reflexive Banach space to its dual is extended for the special case of Sobolev
      spaces to the sum of a pseudomonotone mapping (representing a nonlinear elliptic
      operator) and a strongly nonlinear lower order term.

PMID- 16578770
TI  - Nickel: A micronutrient element for hydrogen-dependent growth of Rhizobium
      japonicum and for expression of urease activity in soybean leaves.
AB  - Soybean plants and Rhizobium japonicum 122 DES, a hydrogen uptake-positive
      strain, were cultured in media purified to remove Ni. Supplemental Ni had no
      significant effect on the dry matter or total N content of plants. However, the
      addition of Ni to both nitrate-grown and symbiotically grown plants resulted in a
      7- to 10-fold increase in urease activity (urea amidohydrolase, EC 3.5.1.5) in
      leaves and significantly increased the hydrogenase activity (EC 1.18.3.1) in
      isolated nodule bacteroids. When cultured under chemolithotrophic conditions,
      free-living R. japonicum required Ni for growth and for the expression of
      hydrogenase activity. Hydrogenase activity was minimal or not detectable in cells
      incubated either without Ni or with Ni and chloramphenicol. Ni is required for
      derepression of hydrogenase activity and apparently protein synthesis is
      necessary for the participation of Ni in hydrogenase expression. The addition of
      Cr, V, Sn, and Pb in place of Ni failed to stimulate the activity of hydrogenase
      in R. japonicum and urease in soybean leaves. The evidence indicates that Ni is
      an important micronutrient element in the biology of the soybean plant and R.
      japonicum.

PMID- 16578773
TI  - Topological and percolation properties of potential mapping with glueing.
AB  - The potential movement of particles forms a continuous mapping of the Lagrangian
      space on the space of Eulerian coordinates of particles. The force-free inertial
      movement with random smooth initial velocity field is considered. The condition
      of particles on caustics glued together to form singularities leads to a peculiar
      structure with localized regions of rarefied matter surrounded by glued surfaces
      with higher-order singularities on them.

PMID- 16578774
TI  - Intrinsic randomness and intrinsic irreversibility in classical dynamical
      systems.
AB  - We continue our previous work on dynamic "intrinsically random" systems for which
      we can derive dissipative Markov processes through a one-to-one change of
      representation. For these systems, the unitary group of evolution can be
      transformed in this way into two distinct Markov processes leading to equilibrium
      for either t--> + infinity or t--> - infinity. To lift the degeneracy, we first
      formulate the second principle as a selection rule that is meaningful in
      intrinsically random systems. For these systems, this excludes a set of
      unrealizable states. As a result of this exclusion, permitted initial conditions
      correspond to a set of states that is not invariant through velocity inversion.
      In this way, the time-reversal symmetry of dynamics is broken and these systems
      acquire a new feature we may call "intrinsic irreversibility." The set of
      admitted initial conditions can be characterized by an entropy displaying the
      amount of information necessary for their preparation. The initial conditions
      selected by the second law correspond to a finite amount of information, while
      the initial conditions that are rejected correspond to an infinite amount of
      information and are therefore "impossible." We believe that our formulation
      permits a microscopic formulation of the second law of thermodynamics for well
      defined classes of dynamical systems.

PMID- 16578777
TI  - Evolutionary principles for polynomial models of frequency-dependent selection.
AB  - A one-locus two-allele deterministic model of frequency-dependent selection is
      analyzed, where genotypic fitnesses [w(i)(q)] are assumed to be nth-degree
      polynomial functions of allelic frequency (q). The model encompasses many modes
      of selection, including intraspecies competitive interaction, brood selection,
      meiotic drive, cyclical selection, and mixed models. Allelic frequencies converge
      monotonically to locally stable equilibria provided that dw(i)(q)/dq is not
      large. There exists a function T(q) that is nondecreasing and locally maximized
      at locally stable equilibria. The rate of change of T(q) per generation is
      approximately equal to the additive genetic variance in fitness. T(q) is a simple
      function of the average effect of an allelic substitution and is closely related
      to Wright's "fitness function." These results define "evolutionary landscapes"
      for some complex selection processes and enlarge the scope of the classical
      methods embodied in Wright's "mean fitness principle" and Fisher's "fundamental
      theorem."

PMID- 16578776
TI  - Catabolite repression of chloroplast development in Euglena.
AB  - Two-dimensional gel electrophoresis resolved total cellular protein from Euglena
      gracilis Klebs var. bacillaris Cori into 640 polypeptides detectable by silver
      staining. The addition of 84 mM ethanol to dark-grown resting carbon-starved
      cells increased the relative amounts of 6 polypeptides and decreased the relative
      amounts of 3 polypeptides. The addition of 84 mM malate to resting cells
      increased the relative amounts of 3 of the ethanol-induced polypeptides,
      suggesting that the induction of these polypeptides represents a generalized
      response to the provision of a utilizable carbon source, a nutritional shift up,
      rather than a specific response to ethanol addition. Exposure of dark-grown
      resting Euglena to light increases the relative amounts of 79 polypeptides
      encoded by the nuclear as well as the chloroplast genome and decreases the
      relative amounts of 72 polypeptides. Ethanol but not malate specifically
      inhibited all of the light-dependent changes in polypeptide levels, indicating
      that chloroplast development in Euglena is a catabolite-sensitive process.

PMID- 16578775
TI  - Nucleotide sequence of a multiple-copy gene for the B protein of photosystem II
      of a cyanobacterium.
AB  - Chloroplast photogene 32 codes for the 32-kilodalton triazine herbicide-binding
      protein at the B site of electron transport in photosystem II of the
      photosynthetic apparatus-its product is the B protein and the gene is accordingly
      designated ps2B here. The cyanobacteria Anacystis nidulans R2, Fremyella
      diplosiphon, and Nostoc sp. MAC each contain several copies of ps2B. The sequence
      of one copy of ps2B from Fremyella, ps2B-1, has been determined. The longest open
      reading frame would code for a protein of 360 amino acids. Although the deduced
      amino acid sequence of ps2B-1 is highly homologous overall to that of the
      corresponding spinach protein [Zurawski, G., Bohnert, H. J., Whitfeld, P. R. &
      Bottomley, W. (1982) Proc. Natl. Acad. Sci. USA 79, 7699-7703] and, excluding
      neutral substitutions, the homology is 95% for an internal segment of 309 amino
      acids, there are a number of nonneutral amino acid substitutions. Most of the
      differences in net charge and polarity occur in the first 20 amino acids at the
      amino terminus and in the amino acid composition at the carboxyl terminus. The
      nucleotide sequences are 76% homologous overall. Conserved sequences resembling
      prokaryotic "-10" and "-35" regions are found at remarkably similar positions in
      the spinach and F. diplosiphon sequences although the surrounding sequences show
      only occasional homologies.

PMID- 16578778
TI  - Structural genes of dinitrogenase and dinitrogenase reductase are transcribed
      from two separate promoters in the broad host range cowpea Rhizobium strain
      IRc78.
AB  - The nucleotide sequence of the structural gene (nifD) coding for the alpha
      subunit of dinitrogenase along with its flanking sequences has been determined in
      cowpea Rhizobium IRc78. The coding sequence consists of 1500 nucleotides, which
      corresponds to a predicted amino acid sequence of 500 residues and a molecular
      weight of 56,025. Nucleotide homology to nifD from the blue-green alga, Anabaena,
      and Parasponia Rhizobium, are 63% and 90%, respectively. Cowpea Rhizobium IRc78
      nifD and nifK (encodes the beta-subunit of dinitrogenase) genes are linked,
      separated by 69 nucleotides. In contrast to fast-growing rhizobia, the structural
      genes of dinitrogenase (nifDK) are transcribed from a different promoter than the
      structural gene of dinitrogenase reductase (nifH). Transcription of nifDK
      initiates 41 nucleotides upstream of the start codon for the nifDK operon. Two
      transcription initiation sites, localized at 152 and 114 nucleotides upstream of
      the start codon, were determined for the nifH operon. Two nucleotide sequences, a
      hexamer (G-G-T-T-G-C) and a pentamer (T-G-G-C-A), centered at approximately -15
      and -25, respectively, are conserved in the nifD and nifH promoter regions and
      are not present in the 69-nucleotide nifDK junction. No sequence homology other
      than a possible ribosome binding site, T-T-G-A-[unk]-G-G-A, located 14
      nucleotides upstream of the initiation codon was detected between the transcribed
      but untranslated leader regions of nifD and nifH.

PMID- 16578779
TI  - Soldier formation regulated by a primer pheromone from the soldier frontal gland
      in a higher termite, Nasutitermes lujae.
AB  - In the nasute higher termite Nasutitermes lujae, the differentiation of new
      soldiers is suppressed or delayed by the soldiers themselves. Experimental data
      strongly suggest that this inhibitory effect results from the action of a primer
      pheromone secreted by the frontal gland of soldiers. The pheromone must be
      contacted directly. Thus, the frontal gland of termite soldiers assumes a new
      role in addition to alarm and defense, although this extension cannot be
      generalized to all termite species. The soldier inhibitory pheromone is evidently
      only one of multiple factors contributing soldier regulation in termite
      societies.

PMID- 16578780
TI  - Estimation of continental Os/Os values by using Os/Os and Nd/Nd ratios in marine
      manganese nodules.
AB  - The relationship between (187)Os/(186)Os and (143)Nd/(144)Nd in different
      manganese nodule fields is used to determine the (187)Os/(186)Os ratio of the
      continental terrains bounding the major ocean basins. The Atlantic Ocean
      drainages yield (187)Os/(186)Os of about 11; the Pacific Ocean, between 25 and
      36; and the western Indian Ocean, 20. By assuming a two-component continental
      crust composed of "ultramafic rocks" (high Os concentration, low (187)Os/(186)Os)
      and "granite" with only radiogenic (187)Os produced in accessory Re-bearing
      molybdenite, the ultramafic contribution to weathering is about 0.2%. Some or
      most of this may come from the alteration of oceanic ultramafics.

PMID- 16578781
TI  - On the construction of nonequatorial minimal hyperspheres in S(1) with stable
      cones in R.
AB  - Within the framework of equivariant differential geometry, we outline the
      construction of some imbedded minimal hyperspheres of S(n)(1) and show that many
      of them have a stable cone in R(n+1). The statement of these and related results
      are given.

PMID- 16578782
TI  - g-Factor of electron centered in symmetric cavity.
AB  - The cyclotron frequency of an electron localized in the center of a cylindrical
      microwave cavity differs slightly from that in free space. To see this, the
      system is modeled by a series resonant lc circuit for the cyclotron motion
      connected across the center of a section of two-wire transmission line (the
      cavity). When the transmission line is infinitely long, its input impedance at
      terminals in its center is strictly ohmic and equal to half its characteristic
      impedance. This ohmic impedance completes the lc circuit, essentially without
      changing its resonant frequency but damping it. This is the analog of the
      cyclotron motion in free space that is damped by spontaneous emission. Free space
      may be mimicked by a short section of transmission line that is terminated at
      both ends by resistors equal in value to its characteristic impedance. A slightly
      lossy cavity is modeled by a section of line terminated by resistors much smaller
      than the characteristic impedance. When the frequency of the lc circuit/cyclotron
      motion is chosen thus that the line/cavity contains exactly an even number of
      half-waves, its input impedance will be ohmic and much smaller than its
      characteristic impedance. Therefore, the frequency of the lc circuit/cyclotron
      motion will be the same as in vacuum but spontaneous emission and associated line
      broadening will be much reduced. The g-factor of the electron measured under
      these conditions practically equals the free space value. This follows because g
      is determined by the ratio of spin and cyclotron frequencies and the spin
      practically does not couple to the radiation field.

PMID- 16578783
TI  - Unusual proton exchange properties of Z-form poly[d(G-C)].
AB  - Real-time solvent-exchange NMR has been used to study the proton exchange in Z
      form poly[d(G-C)]. In 4.5 M NaCl the most slowly exchanging protons (about two
      orders of magnitude slower than in B-DNA) are identified as the guanine imino
      proton and the cytosine amino proton hydrogen bonded to the guanine carbonyl.
      Both protons exchange at the same rate and the exchange follows single
      exponential kinetics and cannot be catalyzed, implying that the exchanges of the
      two protons both occur from the same transient solvent-exposed state. The
      exchange depends strongly on temperature and the activation energy for exchange (
      approximately 22 kcal/mol) is the same as the activation energy for the B --> Z
      transition. The rate of proton exchange is identical with the B --> Z transition
      rate, both measured in 4.5 M NaCl. The correlation between the B --> Z kinetics
      and the proton exchange also extends to 3.25 M NaClO(4) solutions, in which both
      rates are 5 times faster. This unexpected parallelism between the B --> Z
      transition kinetics and the Z exchange kinetics indicates that the rate-limiting
      steps in the two processes are similar.

PMID- 16578784
TI  - Fracture dynamics of fusion of two anti-plane cracks.
AB  - The problem of the fracture dynamics of two two-dimensional coplanar anti-plane
      shear cracks is considered. Both cracks extend under a critical stress-intensity
      fracture criterion. The two cracks are initiated at different locations and
      times. A solution developed by Kostrov [Kostrov, B. V. (1966) J. Appl. Math.
      Mech. 30, 1241-1248] for isolated cracks is used to determine the tearing loci of
      the cracks up to the time at which the individual cracks begin to interact. In
      the interaction interval prior to the fusion of the two cracks, both the stresses
      and the fracture tip loci are determined sequentially by applying the solution to
      Abel's equation twice iteratively. This method can be used to solve problems of
      the fusion of any number of coplanar cracks.

PMID- 16578785
TI  - Fast and slow orientational fluctuations in membranes.
AB  - Fluorescence anisotropy measurements on isotropically distributed membranes yield
      the well-known orientational order parameter as a measure of orientational
      fluctuations of the fluorophore that are fast compared to the fluorescence
      lifetime. Measurements on oriented membranes provide four order parameters, two
      for fast orientational fluctuations and two for slow, from which their
      approximate angular distributions can be derived. This is exemplified for the
      fluctuations of lipids in membranes with and without protein. Steady-state
      fluorescence anisotropy experiments on oriented membranes are carried out, using
      diphenylhexatriene as a fluorescence probe for lipid fluctuations and melittin as
      a membrane protein. Protein molecules in a fluid lipid membrane restrict the fast
      lipid fluctuations and induce slow lipid fluctuations. The angular distribution
      of the slow fluctuations indicates that lipid molecules at the protein surface
      are tilted with respect to the membrane normal. The spatial coherence length of
      these fluctuations is of the order of 15 A.

PMID- 16578786
TI  - Intra- and interspecies transfer and expression of Rhizobium japonicum hydrogen
      uptake genes and autotrophic growth capability.
AB  - Cosmids containing hydrogen uptake genes have previously been isolated in this
      laboratory. Four new cosmids that contain additional hup gene(s) have now been
      identified by conjugal transfer of a Rhizobium japonicum 122DES gene bank into a
      Tn5-generated Hup(-) mutant and screening for the acquisition of Hup activity.
      The newly isolated cosmids, pHU50-pHU53, contain part of the previously isolated
      pHU1 but extend as far as 20 kilobases beyond its border. pHU52 complements five
      of six Hup(-) mutants and confers activity on several Hup(-) wild-type R.
      japonicum strains in the free-living state and where tested in nodules.
      Transconjugants obtained from interspecies transfer of pHU52 to Rhizobium
      meliloti 102F28, 102F32, and 102F51 and Rhizobium leguminosarum 128C53 showed
      hydrogen-dependent methyleneblue reduction, performed the oxyhydrogen reaction,
      and showed hydrogen-dependent autotrophic growth by virtue of the introduced
      genes. The identity of the presumptive transconjugants was confirmed by
      antibiotic-resistance profiles and by plant nodulation tests.

PMID- 16578787
TI  - Developmentally regulated expression of the bean beta-phaseolin gene in tobacco
      seed.
AB  - Recombinant phage lambda177.4 contains a gene for beta phaseolin, a major storage
      glycoprotein of French bean seed. A 3.8-kilobase Bgl II-BamHI fragment containing
      the entire 1700-base-pair coding region, together with 863 base pairs of 5' and
      1226 base pairs of 3' flanking sequence, was inserted into the A66 Ti plasmid of
      Agrobacterium tumefaciens and used to transform tobacco. The level of phaseolin
      in the seeds of plants regenerated from cloned tissue was 1000-fold higher than
      in other tissues. The molecular weight of the phaseolin RNA transcript in tobacco
      seeds was identical to that found in bean seeds. The phaseolin protein in tobacco
      seed was glycosylated and appeared to undergo removal of the signal peptide.
      However, a large proportion of the phaseolin was cleaved into discrete peptides.
      These same peptides were formed as phaseolin was degraded during tobacco seed
      germination. The phaseolin gene appeared to be inserted as a single copy, and the
      proportion of phaseolin per genome copy in tobacco seeds (up to 3% of the total
      embryo proteins) resembled that in the bean seeds (40% of total seed protein,
      expressed from about 14 copies per diploid genome). Furthermore, the transplanted
      gene was turned on during tobacco seed development, and its protein product,
      phaseolin, was localized in the embryonic tissues. Finally, the phaseolin gene
      was inherited as a Mendelian dominant trait in tobacco.

PMID- 16578788
TI  - Purification and amino acid sequence of the ovulation neurohormone of Lymnaea
      stagnalis.
AB  - The neurosecretory caudodorsal cells of the freshwater pulmonate snail Lymnaea
      stagnalis produce an ovulation hormone [caudodorsal cell hormone (CDCH)] that is
      stored and released at the periphery of the intercerebral commissure. In the
      present study, CDCH has been purified and sequenced by micromethods. CDCH has
      been isolated, starting with a hydrochloric acid extract of commissures, by
      chromatofocusing, by high-performance, gel-permeation chromatography, and by
      reversed-phase, high-performance liquid chromatography. This procedure resulted
      in a 1690-fold purification and a 66% recovery. The data of the sequence analysis
      of CDCH are in agreement with the amino acid composition and reveal the following
      sequence of 36 amino acids: H-Leu-Ser-Ile-Thr-Asn-Asp-Leu-Arg-Ala-Ile-Ala-Asp-Ser
      Tyr-Leu-Tyr-Asp-Gln-His -Trp-Leu-Arg-Glu-Arg-Gln-Glu-Glu-Asn-Leu-Arg-Arg-Arg-Phe
      Leu-Glu-Leu-OH. Enzyme data indicate that the COOH end of the hormone is
      amidated. CDCH has a calculated isoelectric point of 9.0 and a calculated M(r) of
      4529. CDCH shares a 44% homology with the sequence of the egg-laying hormone of
      the marine opisthobranch mollusc Aplysia californica.

PMID- 16578789
TI  - Neuroanatomy influences speciation rates among anurans.
AB  - Evolutionary divergence among animal courtship signals is an important component
      of the speciation process. In anurans, the preferential response of females to
      the mating call of conspecific males often maintains reproductive isolation among
      populations. Much of the information in the call is initially processed in the
      inner ear, and there is considerable variation in the structure of this organ
      among lineages of frogs. This variation is responsible for differences in the
      frequency range to which frog species are sensitive and thus influences the
      frequency range over which mating calls can effectively diverge. Data suggest
      that this influence of neuroanatomy on mating call divergence is partly
      responsible for the different rates of speciation among lineages of frogs.

PMID- 16578790
TI  - Alternative adaptations, speciation, and phylogeny (A Review).
AB  - Alternative adaptations-different adaptive phenotypes maintained in the same life
      stage and the same population but not necessarily simultaneously expressed in the
      same individual-represent contrasting character sets produced by the same genome,
      in effect allowing a single species to occupy more than one sympatric niche. Such
      alternatives are particularly likely to give rise to novel adaptations because of
      selection for extreme dissimilarity between them and because established traits
      buffer populations against extinction while independently expressed alternatives
      evolve in new directions. Particular alternatives can be suddenly fixed in
      populations with little or no genetic change, leading to a period of rapid
      evolution (especially, of morphology) exaggerating the characteristics of the
      newly fixed form. This burst of change would facilitate rapid speciation and
      could produce "punctuated" patterns of evolution. Evidence from a wide variety of
      organisms shows that alternative phenotypes are exceedingly common in nature and
      that they are probably important in speciation and macroevolution. Although many
      of these ideas and observations have been noted piecemeal by previous authors,
      bringing them together demonstrates the probable importance of alternative
      adaptations in the origin of major evolutionary novelties and calls for a
      revision of current and traditional ideas about the role of behavior and ontogeny
      in the genesis of organic diversity.

PMID- 16578791
TI  - Absolute electronegativity and hardness correlated with molecular orbital theory.
AB  - The concepts of absolute electronegativity, chi, and absolute hardness, eta, are
      incorporated into molecular orbital theory. A graphic and concise definition of
      hardness is given as twice the energy gap between the highest occupied molecular
      orbital and the lowest unoccupied molecular orbital. Useful correlations can now
      be made between chemical behavior, visible-UV absorption spectra, optical
      polarizability, ionization potentials, and electron affinities.

PMID- 16578792
TI  - Semi-infinite cohomology and string theory.
AB  - We develop the theory of semi-infinite cohomology of graded Lie algebras first
      introduced by Feigin. We show that the relative semi-infinite cohomology has a
      structure analogous to that of the de Rham cohomology in Kahler geometry. We
      prove a vanishing theorem for a special class of modules, and we apply our
      results to the case of the Virasoro algebra and the Fock module. In this case the
      zero cohomology is identified as the physical subspace of the Fock module and the
      no-ghost theorem follows. We reveal the profound relation of semi-infinite
      cohomology theory to the gauge-invariant free string theory constructed by Banks
      and Peskin. We then indicate the connection between gauge-invariant interacting
      string theories and the geometric realizations of the infinite-dimensional Lie
      algebras.

PMID- 16578793
TI  - On the molecular mechanisms of the Schiff base deprotonation during the
      bacteriorhodopsin photocycle.
AB  - Using optical flash photolysis and time-resolved Raman methods, we examined
      intermediates formed during the photocycle of bacteriorhodopsin (bR), as well as
      the bR color change, as a function of pH (in the 7.0-1.5 region) and as a
      function of the number of bound Ca(2+) ions. It is found that at a pH just below
      3 or with less than two bound Ca(2+) per bR, the deprotonation (the L(550) -->
      M(412)) step ceases, yet the K(610) and L(550) analogues are still formed as in
      native bR. The lack of deprotonation in the photocycle of both acid blue and
      deionized blue bR and the similarity of their Raman spectra as well as of their
      K(610) and L(550) analogues strongly suggest that both blue samples have nearly
      the same retinal active site. It is suggested that in both blue species, bound
      cations are removed via a proton-cation exchange equilibrium, either on the
      cation exchange column for the deionized sample or in solution for the acid blue
      sample. The proton-cation exchange equilibrium is found to quantitatively account
      for the pH dependence of the purple-to-blue color change. The different
      mechanisms responsible for the large reduction ( approximately 11 units) of the
      pK(a) value of the protonated Schiff base (PSB) during the photocycle are
      discussed. The absence of the L(550) --> M(412) deprotonation process in both
      blue species is discussed in terms of the previously proposed cation model for
      the deprotonation of the PSB during the photocycle of native bR. The extent of
      the deprotonation and the blue-to-purple color change are found to follow the
      same dependence on either the pH or the amount of cations added to deionized blue
      bR. This observed correlation is briefly discussed.

PMID- 16578794
TI  - Inverted repeat of Olisthodiscus luteus chloroplast DNA contains genes for both
      subunits of ribulose-1,5-bisphosphate carboxylase and the 32,000-dalton Q(B)
      protein: Phylogenetic implications.
AB  - The chloroplast DNA of the chromophytic alga Olisthodiscus luteus has been
      physically mapped with four restriction enzymes. An inverted repeat of 22
      kilobase pairs is present in this 150-kilobase-pair plastid genome. The inverted
      repeat contains the genes for the large and small subunit polypeptides of
      ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39) and also codes for the 32,000
      dalton Q(B) protein. These observations demonstrate that significant differences
      exist in chloroplast genome structure and organization among major plant taxa.

PMID- 16578795
TI  - Dinoflagellate 17S rRNA sequence inferred from the gene sequence: Evolutionary
      implications.
AB  - We present the complete sequence of the nuclear-encoded small-ribosomal-subunit
      RNA inferred from the cloned gene sequence of the dinoflagellate Prorocentrum
      micans. The dinoflagellate 17S rRNA sequence of 1798 nucleotides is contained in
      a family of 200 tandemly repeated genes per haploid genome. A tentative model of
      the secondary structure of P. micans 17S rRNA is presented. This sequence is
      compared with the small-ribosomal-subunit rRNA of Xenopus laevis (Animalia),
      Saccharomyces cerevisiae (Fungi), Zea mays (Planta), Dictyostelium discoideum
      (Protoctista), and Halobacterium volcanii (Monera). Although the secondary
      structure of the dinoflagellate 17S rRNA presents most of the eukaryotic
      characteristics, it contains sufficient archaeobacterial-like structural features
      to reinforce the view that dinoflagellates branch off very early from the
      eukaryotic lineage.

PMID- 16578796
TI  - Evolution of mitochondrial DNA in Drosophila subobscura.
AB  - The colonization of the New World by the Palearctic species Drosophila subobscura
      was first detected in 1978 in South America and around 1982 in western North
      America. The ensuing dramatic expansion of the species, in territory as well as
      numbers, provides an opportunity for studying evolution in a scale rarely
      possible. We have used 10 restriction endonucleases to analyze the mitochondrial
      DNA (mtDNA) of individuals from 23 widely dispersed localities. Only two mtDNA
      composite morphs have been detected in the Americas. None of the two morphs has
      been found in Africa, and only one in the Atlantic islands; but both are
      widespread in Europe, which provides no clue of the precise geographic origin of
      the colonizers. The amount of nucleotide-substitution polymorphism detected in D.
      subobscura is typical for animals, but it is greater in the Old than in the New
      World, presumably due to the recent colonization by a limited number of
      colonizers. Assuming standard evolutionary rates of mtDNA base substitution, the
      mtDNA morphs found in D. subobscura can be traced to a single one that existed no
      less than one million years ago. We argue against the inference that the D.
      subobscura flies now living descend from only one or a few females that lived at
      that time. This type of inference, which we call the "Mother Eve hypothesis," has
      been made to conclude that the human population went through a severe
      constriction about 200,000 years ago, so that all living humans descend from only
      one or a few women who lived at that time. The Mother Eve hypothesis is
      fallacious.

PMID- 16578797
TI  - Extensive variation and heteroplasmy in size of mitochondrial DNA among
      geographic populations of Drosophila melanogaster.
AB  - Size variation and heteroplasmy in mitochondrial DNA (mtDNA) are relatively
      common in natural populations of Drosophila melanogaster. Of 92 isofemale lines
      of flies obtained from various geographic regions throughout the world, 75 lines
      were homoplasmic and showed a total of 12 different mtDNA size classes. The
      remaining 17 lines were heteroplasmic, each line carrying two different mtDNAs,
      and, in all but one case, the mtDNAs in these heteroplasmic lines differed in
      size; a total of nine size classes was represented among them. In cases where one
      type was predominant within an individual, it was usually the smaller mtDNA. This
      finding parallels what was observed in homoplasmic lines, in that the smaller
      mtDNAs were much more common than the larger variants in most populations. The
      data suggest a high rate of mutational occurrence of mtDNA size variants and some
      natural selection against them.

PMID- 16578798
TI  - Discrete wave mechanics: The hydrogen atom with angular momentum.
AB  - A discrete wave mechanical treatment of the hydrogen atom is extended to deal
      with states involving nonzero angular momentum. Only the radial portions of the
      wave vectors are covered. It is predicted that there is a nonzero minimum
      distance between the electron and the nucleus; this threshold distance increases
      with increasing angular momentum. Appropriate finite difference equations are
      formulated. The states with angular momentum exhibit the same degeneracy as do
      corresponding energy levels obtained from solutions of Schrodinger's equation.

PMID- 16578799
TI  - Light-regulated changes in DNase I hypersensitive sites in the rRNA genes of
      Pisum sativum.
AB  - We have examined the rDNA chromatin of Pisum sativum plants grown with or without
      exposure to light for the presence of DNase I hypersensitive sites and possible
      developmental changes in their distribution. Isolated nuclei from pea seedlings
      were incubated with various concentrations of DNase I. To visualize the
      hypersensitive sites, DNA purified from these nuclei was restricted and analyzed
      by gel blot hybridization. We find that several sites exist in both the coding
      and noncoding regions of rDNA repeating units. Several of the sites in the
      nontranscribed spacer region are present in the light but are absent in the dark.
      Conversely, the hypersensitive sites within the mature rRNA coding regions are
      present in the dark but absent in the light. There are two major length variants
      of the rRNA genes in P. sativum var. Alaska. The sites in the nontranscribed
      spacer region that appear during the light treatment occur only in the shorter of
      these two length variants in this cultivar.

PMID- 16578802
TI  - Open discussion of papers by Rohrer, Becker, and Hansma.

PMID- 16578800
TI  - Inhibition of glycolate and D-lactate metabolism in a Chlamydomonas reinhardtii
      mutant deficient in mitochondrial respiration.
AB  - The possibility that glycolate oxidation in unicellular green algae is linked to
      mitochondrial electron transport, rather than to peroxisomal metabolism as in
      higher plants and animals, was studied in a mutant of Chlamydomonas reinhardtii
      (dk97) deficient in cytochrome oxidase. This mutant had normal rates of dark
      respiration (40 +/- 15 mumol of O(2) uptake per hr per mg of chlorophyll) but had
      only 11% of wild-type levels of cytochrome oxidase activity. Salicylhydroxamic
      acid (SHAM) reduced the dark respiration rate of dk97 cells by 71%, but cyanide
      did not significantly inhibit this rate. During photosynthesis in the presence of
      SHAM, glycolate oxidation was blocked, resulting in glycolate accumulation and
      excretion by mutant cells but not by wild-type Chlamydomonas. D-Lactate, which
      accumulated after brief periods of anaerobiosis in Chlamydomonas, was reoxidized
      by air-grown cells only aerobically in the light, and reoxidation of D-lactate
      was blocked by SHAM in the dk97 cells. Thus, glycolate and D-lactate
      dehydrogenase activities are both linked to mitochondrial electron transport in
      Chlamydomonas. During photosynthetic (14)CO(2) fixation by dk97 cells in the
      presence of SHAM, (14)C-labeled tricarboxylic acid cycle intermediates
      accumulated, indicating that, in Chlamydomonas, mitochondrial respiration
      functions during photosynthesis.

PMID- 16578801
TI  - Opening remarks.

PMID- 16578803
TI  - Open discussion of papers by Chu and Muller.

PMID- 16578804
TI  - Open discussion of papers by Birgeneau, Dash, and Pershan.

PMID- 16578806
TI  - Open discussion of papers by McConnell, Rice, and Andelman.

PMID- 16578805
TI  - Open discussion of papers by Stormer, Girvin, and Fowler.

PMID- 16578807
TI  - Open discussion of papers by Israelachvili, Tirrell, and Garoff.

PMID- 16578808
TI  - Open discussion of papers by Lahav, Nuzzo, and McBride.

PMID- 16578809
TI  - Factors determining the average atomic volumes in intermetallic compounds.
AB  - In formation of an intermetallic compound from the elementary metals there is
      usually a contraction in volume. Electron transfer leading to the charge states
      M(+) and M(-) with increase in valence and decrease in volume explains the more
      than 2-fold range in contraction for different compounds in the same binary
      system. In a more thorough analysis, the better packing of atoms of different
      sizes also needs to be considered.

PMID- 16578810
TI  - Alterations in the phenotype of plant cells studied by NH(2)-terminal amino acid
      sequence analysis of proteins electroblotted from two-dimensional gel-separated
      total extracts.
AB  - Phenotypic alterations induced by the cytokinin 6-benzylaminopurine in cell
      suspensions of Nicotiana plumbaginifolia were studied at the level of the NH(2)
      terminal sequence of the constituent proteins. Total protein extracts were
      separated by classical two-dimensional PAGE, and the proteins were recovered by
      electroblotting onto support materials allowing direct gas-phase sequence
      analysis of the immobilized proteins. The systems used consist of an efficient
      electrotransfer buffer (50 mM Tris borate, pH 8.3) in combination with either
      glass-fiber sheets to which poly(4-vinyl-N-methylpyridinium iodide) is adsorbed
      or with membranes of polyvinylidene difluoride. The former is an improved version
      of our previously reported Polybrene-coated glass-fiber sheets and was found to
      be at least twice as efficient as the polyvinylidene difluoride blots. Thirteen
      proteins were selected for analysis. They were either induced, repressed, or
      independent of cytokinin. Ten proteins yielded a sequence, ranging from 10 to 38
      residues. Three of the studied Nicotiana proteins show a degree of homology
      higher than 85% with the amino acid sequences of other eukaryotic proteins-triose
      phosphate isomerase, Mn superoxide dismutase, and (1,3)-beta-glucanase. The
      latter enzyme was repressed by the plant hormone. This study demonstrates that
      proteins associated with phenotypic variations in cells can now be sequenced by a
      straightforward procedure involving two-dimensional gel separation of total
      cellular proteins, recovery by electroblotting, and gas-phase sequence analysis
      of the immobilized proteins.

PMID- 16578811
TI  - Functional regions of the cauliflower mosaic virus 35S RNA promoter determined by
      use of the firefly luciferase gene as a reporter of promoter activity.
AB  - The cauliflower mosaic virus (CaMV) 35S RNA promoter has been dissected and
      examined in a transient expression system using the firefly luciferase gene as a
      reporter of promoter activity. Deletion analysis has shown that the 35S RNA
      promoter is composed of at least three regions-distal, medial, and proximal-which
      are essential for activity. The distal region contains three smaller elements
      homologous to the simian virus 40 "core" enhancer element, the medial region
      possesses a CCAAT-like box, and the proximal region contains a TATA box. A DNA
      segment encompassing the distal region is capable of activating the CaMV 35S core
      promoter in an orientation-independent, but not position-independent, fashion.
      The distal region can also activate a heterologous weak promoter, the CaMV 19S
      RNA promoter, albeit not to the high levels of the 35S RNA promoter. Multimers of
      the distal region are able to activate the 35S RNA promoter core to even greater
      levels of expression than the native 35S promoter. These experiments demonstrate
      that elements outside the boundaries of the core promoter (composed of proximal
      and medial elements) are recognized in a plant cell transient expression system.

PMID- 16578812
TI  - Criteria for regular spacing of reacting Mach stems.
AB  - Nonlinear geometric optics is developed to construct translating self-similar
      high-frequency nonlinear wave patterns as perturbed solutions behind reacting
      shock waves. The geometric conditions involving these wave patterns that yield
      the maximum acoustic amplification lead to criteria for both the formation and
      regular spacing dimension for Mach stems in reacting gases.

PMID- 16578813
TI  - The actinorhizal root-nodule symbiont Frankia sp. strain CpI1 has two glutamine
      synthetases.
AB  - Frankia sp. strain CpI1 has two glutamine synthetases. Glutamine synthetase I
      (GSI) is present during growth on ammonium or N(2) and is similar to classical
      prokaryotic glutamine synthetases. Gel-filtration chromatography gave a molecular
      weight estimate of about 680,000 for the GSI holoenzyme, and denaturing
      polyacrylamide gel electrophoresis yielded a subunit molecular weight of about
      59,000, indicating that GSI is most likely a dodecamer. GSI is regulated by
      adenylylation, as shown by the presence of two spots on two-dimensional
      polyacrylamide gel electrophoresis and by its behavior during treatment with
      snake venom phosphodiesterase. GSII is derepressed during nitrogen starvation and
      accounts for about 95% of the glutamine synthetase activity in nitrogen-starved
      cells. It is heat-labile and has a subunit molecular weight of about 43,000.
      Frankia GSII is similar to GSII enzymes found in all but one member of the
      Rhizobiaceae analyzed to date. The presence of a second glutamine synthetase in
      Frankia lends support to the proposal that symbiotic organisms have unique modes
      of nitrogen nutrition but reopens questions about the origins and uniqueness of
      GSII genes in members of the Rhizobiaceae.

PMID- 16578814
TI  - Exciton interactions in reaction centers of the photosynthetic bacterium
      Rhodopseudomonas viridis probed by optical triplet-minus-singlet polarization
      spectroscopy at 1.2 K monitored through absorbance-detected magnetic resonance.
AB  - Linear dichroic triplet-minus-singlet [LD-(T - S)] spectra of isolated reaction
      centers of the photosynthetic bacterium Rhodopseudomonas viridis have been
      measured at 1.2 K with the linear dichroic absorbance-detected magnetic resonance
      (LD-ADMR) technique for two mutually perpendicular directions of the preferred
      axis. The LD-(T - S) spectra have been calibrated with respect to the
      corresponding (T - S) spectra as a function of applied microwave power and
      quantitatively interpreted using the formalism of photoselection. The transition
      moment of the optical transition at 1007 nm makes angles of 72 degrees +/- 5
      degrees and 15 degrees +/- 5 degrees with the triplet x and y spin axes,
      respectively. The experimental spectra have been simulated employing exciton
      theory and using the atomic coordinates of the resolved crystal structure of the
      reaction center. The spectral interpretation yields the angles between the
      transition moments of the various absorption bands of the (T - S) spectra and the
      triplet axes, and between the moments themselves, with the triplet state of the
      primary donor (3)P localized on the P-bacteriochlorophyll b in the "active" (L)
      chain.

PMID- 16578815
TI  - Integration of Agrobacterium tumefaciens transfer DNA (T-DNA) involves
      rearrangements of target plant DNA sequences.
AB  - The transfer DNA (T-DNA) mobilized into plant cells by Agrobacterium tumefaciens
      seems to integrate rather randomly into the plant genome. We analyzed a target
      site in the genome of Nicotiana tabacum before and after integration of a T-DNA.
      Clones presenting right and left T-DNA/plant DNA junctions were used as probes to
      identify and isolate a unique 1.8-kilobase EcoRI fragment corresponding to the
      plant DNA target site for a T-DNA insertion event. Comparison of the nucleotide
      sequences of the plant DNA portions of the T-DNA junction clones with the
      original plant DNA target revealed that several types of rearrangements resulted
      from insertion of the T-DNA. The most dramatic alteration was a 158-base-pair
      direct repeat of target plant sequences at the left and right T-DNA junctions. In
      addition, there were deletion and insertion events at the ends of the right and
      left copies of the 158-base-pair repeat. The variety of target-site
      rearrangements suggests that T-DNA insertion is a multistep process of
      recombination accompanied by local replicative and repair activities mediated by
      host-cell enzymes.

PMID- 16578816
TI  - DNA sequences required for anaerobic expression of the maize alcohol
      dehydrogenase 1 gene.
AB  - Expression of the maize alcohol dehydrogenase 1 (Adh1) gene is transcriptionally
      regulated under conditions of anaerobic stress. DNA sequences required for the
      expression of Adh1 have been identified by a functional analysis of in vitro
      constructed hybrid genes consisting of the Adh1 promoter fused to the
      chloramphenicol acetyltransferase coding region. A series of 5' deletions, 3'
      deletions, hybrid promoters, and linker scanning mutants of the Adh-CAT hybrid
      gene were introduced into maize protoplasts by electroporation and assayed for
      chloramphenicol acetyltransferase activity after incubation of the protoplasts
      under different oxygen tensions. The results indicate that a 40-base-pair DNA
      sequence within the Adh1 promoter is required for anaerobically regulated
      expression of the hybrid gene. Clustered point mutations in this sequence show
      that it is composed of two essential regions, each approximately 15 base pairs,
      separated by a 10-base-pair DNA sequence that does not appear to be important for
      anaerobic expression. Attachment of this 40-base-pair element to an unrelated
      promoter shows that this DNA sequence is both necessary and sufficient for
      induction of gene expression by low oxygen stress.

PMID- 16578818
TI  - Isolation and characterization of a cDNA clone encoding wheat germ agglutinin.
AB  - Two sets of synthetic oligonucleotides coding for amino acids in the amino- and
      carboxyl-terminal portions of wheat germ agglutinin were synthesized and used as
      hybridization probes to screen cDNA libraries derived from developing embryos of
      tetraploid wheat. The nucleotide sequence for a cDNA clone recovered from the
      cDNA library was determined by dideoxynucleotide chain-termination sequencing in
      vector M13. The amino acid sequence deduced from the DNA sequence indicated that
      this cDNA clone (pNVR1) encodes isolectin 3 of wheat germ agglutinin. Comparison
      of the deduced amino acid sequence of clone pNVR1 with published sequences
      indicates isolectin 3 differs from isolectins 1 and 2 by 10 and 8 amino acid
      changes, respectively. In addition, the protein encoded by pNVR1 extends 15 amino
      acids beyond the carboxyl terminus of the published amino acid sequence for
      isolectins 1 and 2 and includes a potential site for N-linked glycosylation.
      Utilizing the insert of pNVR1 as a hybridization probe, we have demonstrated that
      the expression of genes for wheat germ agglutinin is modulated by exogenous
      abscisic acid. Striking homology is observed between wheat germ agglutinin and
      chitinase, both of which are proteins that bind chitin.

PMID- 16578817
TI  - Overproduction and purification of the luxR gene product: Transcriptional
      activator of the Vibrio fischeri luminescence system.
AB  - Expression of Vibrio fischeri luminescence genes requires an inducer, termed
      autoinducer, and a positive regulatory element, the luxR gene product. A plasmid
      containing luxR under control of a tac promoter was engineered to overproduce
      this gene product. The overproduced luxR gene product was active in vivo, and its
      apparent monomeric molecular weight was indistinguishable from that of the
      protein encoded by luxR under control of its own promoter (M(r) 27,000). The new
      tac-luxR construct directed the synthesis of large quantities of the luxR gene
      product in induced Escherichia coli cells lacking other lux genes. In the
      presence of the other lux genes, overexpression of the tac-luxR construct was not
      detected. The overproduced luxR gene product, which formed cytoplasmic inclusion
      bodies, was purified and used in subsequent studies. Nonequilibrium pH gradient
      electrophoresis indicated that the protein was basic, and the amino-terminal 15
      amino acids were sequenced. DNA-binding activity was detected by membrane filter
      binding assays; under the conditions used, the binding was not lux DNA-specific.
      Binding of tritium-labeled autoinducer to the luxR gene product was not detected,
      and autoinducer enhancement of the binding of the luxR gene product to DNA could
      not be detected reproducibly.

PMID- 16578819
TI  - Biological function of pathogenesis-related proteins: Four tobacco pathogenesis
      related proteins are chitinases.
AB  - Four endochitinases (poly[1,4-(N-acetyl-beta-D-glucosaminide)] glycanohydrolase,
      EC 3.2.1.14) have been purified from leaves of Nicotiana tabacum cv. Samsun NN
      reacting hypersensitively to tobacco mosaic virus. Two of them are acidic
      proteins of molecular weights 27,500 and 28,500 and have been identified as 2 of
      the 10 pathogenesis-related proteins that are known to accumulate in tobacco in
      response to stress or pathogen attack. These two pathogenesis-related proteins,
      named "P" and "Q" when their biological function was unknown, account for one
      third of tobacco mosaic virus-induced chitinase activity of tobacco leaves. They
      are serologically closely related to the two other chitinases, which can be
      considered as new basic pathogenesis-related proteins. These two basic chitinases
      exhibit higher molecular weights (32,000 and 34,000) and higher specific enzyme
      activity than the two acidic isoforms.

PMID- 16578821
TI  - Role of cytoplasm-specific introgression in the evolution of the polyploid
      wheats.
AB  - Studies of N-banded mitotic and meiotic karyotypes of Triticum turgidum L. (2n =
      28; AABB) and Triticum timopheevii Zhuk. (2n = 28; AAGG) and hybrids between
      them, along with observations of meiotic pairing between telocentrics of the AB
      genome chromosomes and their respective homologues and homeologues in T.
      timopheevii, showed that chromosome 4 (m4) of Triticum monococcum L. is present
      (as 4A(t)) in T. timopheevii but is lacking in T. turgidum. Neither 4A nor 4B
      pairs with 4A(t), but 4A pairs with 4G and, for this reason and because of its
      banding pattern, must be considered a B-genome chromosome. T. timopheevii
      chromosomes 4A(t) and 3A(t) are involved in a reciprocal translocation, and
      2A(t), 1G, 2G, and 5G are also involved in translocations. Chromosome arm 4BL
      occasionally pairs with 7G. The satellites are on the short arms of chromosomes
      6A(t) and 6G of T. timopheevii and 1B and 6B of T. turgidum. It is suggested that
      (i) T. timopheevii orginated as an allotetraploid of Aegilops speltoides
      Tausch/T. monococcum and (ii) T. turgidum was derived from T. timopheevii by
      introgressive hybridization with an unknown diploid species, which contributed
      its distinctive cytoplasm, chromosome 4B or a substantial portion of it, and
      additional chromosome segments. Rapid fixation of 4B in T. turgidum was ensured
      by cytoplasm-specific transmission.

PMID- 16578820
TI  - Bacterial phytotoxin, syringomycin, induces a protein kinase-mediated
      phosphorylation of red beet plasma membrane polypeptides.
AB  - Syringomycin, a peptide toxin and a virulence factor produced by the bacterial
      phytopathogen Pseudomonas syringae pv. syringae, stimulated the phosphorylation
      of several plasma membrane polypeptides of red beet storage tissue. Among these
      was a 100-kDa polypeptide, which corresponds in size to the proton pump ATPase.
      The phosphorylations were insensitive to hydroxylamine, indicating that the
      polypeptide phosphorylated intermediates involved phosphate ester bonds
      characteristic of protein kinase-mediated phosphorylation. Phosphorylation of the
      100-kDa polypeptide and of most of the other polypeptides was reduced or
      eliminated by extraction of the membranes with 0.1% (wt/vol) sodium deoxycholate,
      a treatment that also eliminated the ability of the toxin to stimulate ATPase
      activity. Phosphorylation of the 100-kDa polypeptide was highest with 10-20 mug
      of syringomycin; the same amounts gave the highest degree of ATPase activity
      stimulation. Phosphorylation of some of the polypeptides was eliminated or
      decreased by the Ca(2+) chelator EGTA. Addition of excess Ca(2+) restored the
      phosphorylation of most of these polypeptides. We conclude that syringomycin acts
      by stimulating an endogenous membrane protein kinase activity, which results in
      the phosphorylation of several membrane polypeptides. One of the phosphorylated
      polypeptides corresponds in size to the proton pump ATPase.

PMID- 16578822
TI  - Isotropic probability measures in infinite-dimensional spaces.
AB  - Every isotropic probability measure on the space R(infinity) of real sequences x
      = (x(1), x(2),...) is a convex combination of the measure concentrated at 0 and a
      member of I(0)(R(infinity)), the set of all isotropic probability measures
      p(infinity) on R(infinity) with p(infinity)({0}) = 0. Each p(infinity) [unk]
      I(0)(R(infinity)) is completely determined by any one of its finite-dimensional
      marginal distributions p(n). Each p(n) has a density function f(n) with
      dp(n)(x(1),..., x(n)) = dx(1)... dx(n)f(n)(x(1) (2) +... + x(n) (2)). Each f(n)
      is completely monotone in 0 < xi < infinity (hence analytic in the right complex
      xi half-plane), and pi(n/2)Gamma(n/2)(-1) (0) (infinity)dxi xi(n/2-1)f(n)(xi) =
      1. Every f that satisfies these two conditions is f(n) for a unique p(infinity)
      [unk] I(0)(R(infinity)). Hence the equation pi(xi) (infinity)dzeta f(2)(zeta) =
      (0) (infinity)dmu (t)e(-txi) defines a bijection between I(0)(R(infinity)) and
      the set of all probability measures mu on 0 </= t < infinity. If p(infinity)
      [unk] I(0)(R(infinity)) then p(infinity)({x: Sigma(i=1) (infinity)x(i) (2) <
      infinity}) = 0, so p(infinity) is not a "softened" or "fuzzy" version of the
      inequality Sigma(i=1) (infinity)x(i) (2) </= 1. If the prior information in a
      linear inverse problem consists of this inequality and nothing else, stochastic
      inversion and Bayesian inference are both unsuitable inversion techniques.

PMID- 16578823
TI  - Single-stranded DNA from abutilon mosaic virus is present in the plastids of
      infected Abutilon sellovianum.
AB  - The leaf mosaic of Abutilon sellovianum is caused by abutilon mosaic virus
      (AbMV), a geminivirus that has a circular single-stranded DNA genome. DNA was
      isolated from intact plastids of AbMV-infected and noninfected plants. Plastids
      from infected plants were shown to contain the single-stranded AbMV DNA by
      Southern-blot hybridization experiments that used a probe made from highly
      purified AbMV DNA. The possibility of adsorption of AbMV virions or viral DNA
      onto the plastid envelope was ruled out by several in vitro experiments with
      DNase I and protease. Furthermore, the lamellar system of plastids from AbMV
      infected plants was degenerated and substituted by amorphous electron-dense
      material. The transport of AbMV DNA across the plastid envelope has implications
      for the development of a chloroplast transformation vector.

PMID- 16578824
TI  - Genetic transfer in Desulfovibrio desulfuricans.
AB  - An apparently defective bacteriophage capable of mediating transduction has been
      identified in culture filtrates of Desulfovibrio desulfuricans (American Type
      Culture Collection 27774). Phage-mediated intraspecies transfer of antibiotic
      resistance markers occurs with a frequency of 10(-5) to 10(-6) per recipient
      cell. The vector contains linear fragments of double-stranded DNA of about 13.5
      kilobase pairs, which appear to be random pieces of bacterial DNA. As yet,
      neither induction nor plaque formation has been observed. To our knowledge, a
      system of genetic exchange has not been described before for a member of the
      sulfate-reducing bacteria.

PMID- 16578825
TI  - Stark effect spectroscopy of Rhodobacter sphaeroides and Rhodopseudomonas viridis
      reaction centers.
AB  - The nature of the initially excited state of the primary electron donor or
      special pair has been investigated by Stark effect spectroscopy for reaction
      centers from the photosynthetic bacteria Rhodopseudomonas viridis and Rhodobacter
      sphaeroides at 77 K. The data provide values for the magnitude of the difference
      in permanent dipole moment between the ground and excited state,
      [unk]Deltamu[unk], and the angle [unk] between Deltamu and the transition dipole
      moment for the electronic transition. [unk]Deltamu[unk] and [unk] for the lowest
      energy singlet electronic transition associated with the special pair primary
      electron donor were found to be very similar for the two species.
      [unk]Deltamu[unk] for this transition is substantially larger than for the Q(y)
      transitions of the monomeric pigments in the reaction center or for pure
      monomeric bacteriochlorophylls, for which Stark data are also reported. We
      conclude that the excited state of the special pair has substantial charge
      transfer character, and we suggest that charge separation in bacterial
      photosynthesis is initiated immediately upon photoexcitation of the special pair.
      Data for Rhodobacter sphaeroides between 340 and 1340 nm are presented and
      discussed in the context of the detection of charge-transfer states by Stark
      effect spectroscopy.

PMID- 16578826
TI  - Tree species richness of upper Amazonian forests.
AB  - Upper Amazonian data for tree species richness in 1-hectare plots are reported.
      All plants >/=10 cm diameter were censused and identified in six plots in
      Amazonian Peru and one on the Venezuela-Brazil border. The two plots from the
      everwet forests near Iquitos, Peru, are the most species-rich in the world, with
      approximately 300 species >/=10 cm diameter in single hectares; all of the
      Peruvian plots are among the most species-rich ever reported. Contrary to
      accepted opinion, upper Amazonian forest, and perhaps Central African ones, have
      as many or more tree species as comparable Asian forests. Very high tree species
      richness seems to be a general property of mature lowland evergreen forests on
      fertile to moderately infertile soils on all three continents.

PMID- 16578827
TI  - A point mutation in the tobacco mosaic virus capsid protein gene induces
      hypersensitivity in Nicotiana sylvestris.
AB  - In Nicotiana sylvestris, the N' gene confers hypersensitive resistance to some
      strains of tobacco mosaic virus (TMV) but not to the common strain. TMV sequences
      responsible for inducing local lesion formation in this host were identified by
      using cDNA clones to construct genomic recombinants between the common strain
      genome and a local-lesion-inducing mutant. To assay for sequences conferring the
      mutant phenotype, in vitro transcripts of recombinants were inoculated onto
      leaves of N. sylvestris and observed for the formation of either local lesions or
      a systemic infection. Sequences from the mutant that converted the hybrid genome
      to the mutant phenotype were located between nucleotides 5972 and 6206. Sequence
      analysis of this region revealed point mutations in the mutant at nucleotides
      6157 (cytosine to uracil) and 6199 (adenine to guanine). The mutation at 6157
      changes the capsid protein gene to specify phenylalanine rather than serine at
      position 148; nucleotide 6199 occurs in the 3' nontranslated region. When each
      point mutation was individually substituted into the wild-type background,
      transcripts containing only the alteration at 6157 produced local lesions on N.
      sylvestris, whereas transcripts containing only the alteration at 6199 produced
      systemic mosaic symptoms. The frequency of mutation was examined by partially
      sequencing virion RNA from six additional independent local-lesion mutants. Five
      mutants had the same alteration at 6157 as the original mutant and none had the
      alteration at 6199. This work demonstrates that the capsid protein gene of TMV is
      multifunctional, both encoding the virion structural protein and mediating the
      outcome of infection in N. sylvestris.

PMID- 16578828
TI  - Cauliflower mosaic virus gene VI produces a symptomatic phenotype in transgenic
      tobacco plants.
AB  - Gene VI of the cauliflower mosaic virus (CaMV) genome encodes a protein (P(66))
      in virus-infected plants that accumulates in cytoplasmic inclusion bodies. When a
      segment of the CaMV genome bearing gene VI is transferred to tobacco plants by
      the Agrobacterium tumefaciens Ti plasmid, the resulting transgenic plants display
      viral-like symptoms. Symptoms produced by the DNA from two different viral
      isolates (CaMV Cabb B-JI and CM1841) were distinct-symptoms from the first were
      mosaic-like, whereas the other caused uniform bleaching of leaves. That gene VI
      was responsible for the symptomatic phenotype was demonstrated by showing that
      symptom production was blocked by deletions and by a frame-shifting linker
      mutation in gene VI. Furthermore, in primary transformants, there was a strict
      correlation between the appearance of symptoms and the presence of gene VI
      product, P(66), detected by immunoblots. Hence, a protein encoded by the CaMV
      genome produces viral-like symptoms in transgenic tobacco plants.

PMID- 16578829
TI  - Several "pathogenesis-related" proteins in potato are 1,3-beta-glucanases and
      chitinases.
AB  - Chitinase {poly[1,4-(N-acetyl-beta-D-glucosaminide)]glycanohydrolase, EC
      3.2.1.14} and 1,3-beta-glucanase (1,3-beta-D-glucan 3-glucanohydrolase, EC
      3.2.1.6) activities increased rapidly in potato (Solanum tuberosum) leaves
      inoculated with the pathogenic fungus Phytophthora infestans or treated with
      fungal elicitor. The enzyme activities were resolved into a total of two distinct
      1,3-beta-glucanases and six proteins with chitinase activity. By several
      criteria, all of these proteins are classified as "pathogenesis-related" proteins
      whose biochemical functions have so far been unknown. Some of them constitute a
      major portion of the proteins accumulating in the intercellular space of infected
      potato leaves and are assumed to play an important role in pathogen defense.

PMID- 16578830
TI  - On a notion of simplicial depth.
AB  - For a distribution F on R(p) and a point x in R(p) the simplicial depth D(x),
      which is the probability that x be inside a random simplex whose vertices are p +
      1 independent observations from F, is introduced. D(x) can be viewed as a measure
      of depth of the point x relative to F, and its empirical version gives rise to a
      natural ordering of the data points from the center outward. This ordering
      provides an approach for detecting outliers in a multivariate data cloud and
      leads to the introduction of affine equivariant multivariate generalizations of
      the univariate sample median and L-statistics. This sample median is shown to be
      consistent for the center of any angularly symmetric distribution.

PMID- 16578831
TI  - Complex foraging polymorphism in bluegill sunfish.
AB  - The bluegill sunfish (Lepomis macrochirus) is considered a generalist predator,
      adept at feeding in both the littoral and open-water habitats of North American
      freshwater lakes. We demonstrate adaptive intraspecific variation in morphology
      and foraging behaviors within single lakes. This variation appears to make
      individual fish specialized for feeding in either the littoral or open-water
      habitat. Discovery of a complex polymorphism in such a well-studied species
      suggests that adaptive variation may be more common than is currently perceived.

PMID- 16578832
TI  - Discrete mechanics and special relativistic random walks.
AB  - Random walks with step lengths equal to the shortest possible physically
      meaningful distances are considered from the point of view of special relativity
      involving two observers moving uniformly with respect to each other. A
      requirement of statistical equivalence of the probability distributions seen by
      those observers leads to the Lorentz transformations, provided a randomly moving
      particle shifts from one submicroscopic cell of uncertainty to a neighbor with a
      speed equivalent to that of light. Ordinary smooth motion would appear to involve
      a tremendous amount of submicroscopic back and forth randomness subject to a
      statistical bias favoring a particular direction. The diffusive nature of the
      motion naturally leads to a spreading of the probability distribution.

PMID- 16578834
TI  - Relativistic cyclotron resonance shape in magnetic bottle geonium.
AB  - The thermally excited axial oscillation of the electron through the weak magnetic
      bottle needed for the continuous Stern-Gerlach effect modulates the cyclotron
      frequency and produces a characteristic approximately 12-kHz-wide vertical rise
      exponential decline line shape of the cyclotron resonance. At the same time the
      relativistic mass shift decreases the frequency by approximately 200 Hz per
      cyclotron motion quantum level n. Nevertheless, our analysis of the complex line
      shape shows that it should be possible to produce an abrupt rise in the cyclotron
      quantum number n from 0 to approximately 20 over a small fraction of 200 Hz, when
      the 160-GHz microwave drive approaches the n = 0 --> 1 transition, and a jump of
      14 levels over a frequency increment of 200 Hz has already been observed in
      preliminary work. This realizes an earlier proposal to generate a very sharp
      cyclotron resonance feature by quasithermal excitation with a square noise band
      and should provide a way to detect spin flips when a weak bottle is used to
      reduce the broadening of the g - 2 resonance by a factor of 20.

PMID- 16578833
TI  - In situ localization of light-induced chalcone synthase mRNA, chalcone synthase,
      and flavonoid end products in epidermal cells of parsley leaves.
AB  - Methods involving in situ RNA hybridization, immunohistochemistry, and
      microspectrophotometry of individual cells were used to localize the mRNA
      encoding chalcone synthase (the key enzyme of flavonoid biosynthesis), the enzyme
      protein, and the biosynthetic end products in cross sections of parsley leaves
      (Petroselinum crispum). The light-dependent, sequential occurrence of all three
      components was restricted to epidermal cells. The results are in agreement with
      the putative function of flavonoids (transcriptionally inducible, UV-protective
      pigments) and suggest that all biosynthetic steps occur in those cells in which
      the products accumulate.

PMID- 16578835
TI  - Carotenoid biosynthesis: Isolation and characterization of a bifunctional enzyme
      catalyzing the synthesis of phytoene.
AB  - Phytoene is the first C(40) intermediate in the biogenesis of carotenoids. It is
      formed by two enzyme activities, catalyzing (i) the coupling of two molecules of
      geranylgeranyl diphosphate to yield prephytoene diphosphate and (ii) the
      conversion of prephytoene diphosphate into phytoene. We show now, with Capsicum
      chromoplast stroma, that the overall activity resides in a single protein, which
      has been purified to homogeneity by affinity chromatography. The monomeric
      structure and the molecular size (M(r) 47,500) were demonstrated by
      NaDodSO(4)/PAGE and glycerol gradient centrifugation. Further characterization
      was achieved by using specific antibodies which allowed immunofractionation and
      immunoprecipitation of the enzymatic activity from chromoplast stroma. The two
      reactions followed conventional Michaelis-Menten kinetics, with K(m) values of
      0.30 muM and 0.27 muM, respectively, for geranylgeranyl diphosphate and
      prephytoene diphosphate. The activity of the enzyme depends strictly upon the
      presence of Mn(2+). This selectivity may be one of the factors regulating the
      competition with potentially rival enzymes converting geranylgeranyl diphosphate
      into other plastid terpenoids. The two enzymatic reactions were inhibited by
      inorganic pyrophosphate and by the arginine-specific reagent
      hydroxyphenylglyoxal. In no instance were the two reactions kinetically
      uncoupled. These properties strongly suggest that the same enzyme catalyzes the
      two consecutive reactions, and we propose to name it phytoene synthase.

PMID- 16578836
TI  - Directed mutations affecting spectroscopic and electron transfer properties of
      the primary donor in the photosynthetic reaction center.
AB  - Oligonucleotide-mediated mutagenesis has been used to change the histidine
      residues that act as axial ligands to the central Mg(2+) ions of the "special
      pair" bacteriochlorophylls in the reaction center of Rhodobacter capsulatus.
      Histidine-173 of the L subunit has been replaced with glutamine, while histidine
      200 of the M subunit has been replaced with glutamine, leucine, or phenylalanine.
      When leucine or phenylalanine is introduced at M200, one of the special pair
      bacteriochlorophylls is converted to bacteriopheophytin, which generates a
      heterodimer at the special pair binding site. The pigment composition of the
      reaction center is unaltered when either histidine is replaced with glutamine.
      All of these mutant reaction centers are photochemically active, although the
      electron transfer properties of heterodimer-containing reaction centers are
      altered. These mutations begin to define the structural parameters that determine
      whether bacteriochlorophyll or bacteriopheophytin will be incorporated into the
      tetrapyrrole binding sites of the photosynthetic reaction center. Our results
      demonstrate that the properties of the photosynthetic reaction center can be
      changed by directed mutagenesis, which makes this complex an excellent model for
      testing theories of electron transfer in biological systems.

PMID- 16578837
TI  - How to Prepare a Manuscript for PNAS.

PMID- 16578838
TI  - Cloned avirulence genes from the tomato pathogen Pseudomonas syringae pv. tomato
      confer cultivar specificity on soybean.
AB  - Three different cosmid clones were isolated from a genomic library of the tomato
      pathogen Pseudomonas syringae pv. tomato, which, when introduced into the soybean
      pathogen P. syringae pv. glycinea, caused a defensive hypersensitive response
      (HR) in certain soybean cultivars. Each clone was distinguished by the specific
      cultivars that reacted hypersensitively and by the intensity of the HR elicited.
      Unlike wild-type P. syringae pv. tomato isolates, which elicit the HR on all
      soybean cultivars, all three clones exhibited cultivar specificities analogous to
      avirulence genes previously cloned from P. syringae pv. glycinea. However, the
      collective phenotypes of the three clones accounted for HRs on all tested soybean
      cultivars. One of the three P. syringae pv. tomato clones contained an avirulence
      gene homologous to avrA, which was previously cloned from P. syringae pv.
      glycinea race 6. The other two P. syringae pv. tomato clones expressed unique HR
      patterns on various soybean cultivars, which were unlike those caused by any
      known P. syringae pv. glycinea race or previously cloned P. syringae pv. glycinea
      avr gene. Further characterization of the second P. syringae pv. tomato clone
      indicated that the avirulence phenotype resided on a 5.6-kilobase HindIII
      fragment that, in Southern blot analyses, hybridized to an identical-size
      fragment in various P. syringae pathovars, including all tested glycinea races.
      These results demonstrate that avirulence genes may be distributed among several
      P. syringae pathovars but may be modified so that the HR is not elicited in a
      particular host plant. Furthermore, the data raise the possibility that
      avirulence genes may function in host-range determination at levels above race
      cultivar specificity.

PMID- 16578839
TI  - Principles determining the structure of high-pressure forms of metals: The
      structures of cesium(IV) and cesium(V).
AB  - Consideration of the relation between bond length and bond number and the average
      atomic volume for different ways of packing atoms leads to the conclusion that
      the average ligancy of atoms in a metal should increase when a phase change
      occurs on increasing the pressure. Minimum volume for each value of the ligancy
      results from triangular coordination polyhedra (with triangular faces), such as
      the icosahedron and the Friauf polyhedron. Electron transfer may permit atoms of
      an element to assume different ligancies. Application of these principles to
      Cs(IV) and Cs(V), which were previously assigned structures with ligancy 8 and 6,
      respectively, has led to the assignment to Cs(IV) of a primitive cubic unit cell
      with a = 16.11 A and with about 122 atoms in the cube and to Cs(V) of a primitive
      cubic unit cell resembling that of Mg(32)(Al,Zn)(49), with a = 16.97 A and with
      162 atoms in the cube.

PMID- 16578840
TI  - Comparative study of optical absorption and circular dichroism of
      bacteriochlorophyll oligomers in Triton X-100, the antenna pigment B850, and the
      primary donor P-860 of photosynthetic bacteria indicates that all are similar
      dimers of bacteriochlorophyll a.
AB  - Dimers of bacteriochlorophyll a (Bchla) with optical absorption maximum at 853 nm
      and a nonconservative circular dichroism spectrum are formed in a solution of
      formamide/water that contains micelles of Triton X-100. The apparent equilibrium
      constant and the corresponding Gibbs energy change for the Bchl self-organization
      are 4.9 x 10(6) M(-1) and -9.2 kcal/mol, respectively. The experimental
      absorption and circular dichroism spectra of the in vitro Bchl dimer (termed Bchl
      853) are similar to the spectra of the bacterial light-harvesting complex B850
      and the primary electron donor P-860 and probably point to a common structural
      motif. Indeed, simulation of the dimers' spectra (optical absorption and circular
      dichroism), achieved by using an extended version of the exciton theory, suggests
      the same geometry as recently elucidated for P-860 by x-ray diffraction
      crystallography. The proposed geometry is predicted to have the minimum energy in
      the gas phase. In conclusion, the spectral properties of the bathochromically
      shifted forms of Bchla are likely a result of strong dipolar interactions in self
      organized structures of Bchls.

PMID- 16578841
TI  - Specific localization of a plant cell wall glycine-rich protein in protoxylem
      cells of the vascular system.
AB  - An antibody against glycine-rich protein 1.8 of bean (Phaseolus vulgaris L.) was
      used for immunogold/silver localization of the protein in different organs of the
      plant. In hypocotyls, ovaries, and seed coats, the protein was found specifically
      in xylem cells of the vascular tissue. In hypocotyls, only protoxylem cells were
      labeled with the antibody, which indicates a remarkable cell-type specificity for
      accumulation of this cell wall protein. In mature hypocotyls, the protein was
      restricted to the same subset of xylem cells but was no longer detected on tissue
      prints, where a positive antibody reaction depends on the transfer of soluble
      material from plant tissue to the nitrocellulose filter. This indicates that the
      glycine-rich protein is insolubilized in the cell wall during development. In
      longitudinal sections of tracheary elements of young hypocotyls and seed coats,
      the antibody stained a pattern very similar to that of the lignified secondary
      thickenings of the cell wall, which suggests a close functional relationship
      between glycine-rich protein and lignin deposition during cell wall biogenesis in
      protoxylem cells.

PMID- 16578842
TI  - In vitro phosphorylation of plant plasma membrane proteins in response to the
      proteinase inhibitor inducing factor.
AB  - A polygalacturonide purified from a tomato leaf pectic polysaccharide that
      induces the systemic synthesis of proteinase inhibitors in tomato plants enhances
      the phosphorylation of specific proteins in plasma membrane fractions isolated
      from tomato and potato leaves. In tomato plasma membranes, two proteins of 34 and
      29 kDa show enhanced phosphorylation in response to the polyuronide. In potato
      plasma membranes, only a protein of 34 kDa exhibited enhanced phosphorylation due
      to the polyuronide. A noncarbohydrate class of proteinase inhibitor inducing
      factor, recently identified by workers in this laboratory, resulted in the in
      vitro hyperphosphorylation of a family of proteins of approximately 27 kDa. The
      phosphorylation of specific polypeptides in leaves in response to the same
      factors that induce the expression of proteinase inhibitor genes suggests that
      protein kinases may play an important role in the mechanism of signal
      transduction leading to defense gene expression.

PMID- 16578843
TI  - Blue-light regulation of transcription for nuclear genes in pea.
AB  - The expression of many nuclear genes in plants is light regulated. Previous
      investigations have shown that the excitation of phytochrome can affect
      transcription rate and steady-state RNA levels for several of these genes. No
      direct demonstration of the effects of blue light has been reported. We have
      identified several nuclear genes in pea whose transcription rate and steady-state
      RNA levels are affected by a single pulse of blue light. Pea seedlings, grown in
      continuous red light to saturate any phytochrome response, were treated with a
      single pulse (10(3) mumol.m(-2)) of blue light 6 days after planting. The blue
      light treatment resulted in an increase in the steady-state RNA level and rate of
      transcription for the Cab (chlorophyll a/b binding protein) gene family and a
      decrease in the steady-state RNA level and the rate of transcription for the gene
      families corresponding to cDNA clones pEA25 and pEA207. Changes in the rate of
      transcription for Cab and pEA207 are apparent within 3 hr of the blue-light
      treatment.

PMID- 16578844
TI  - Tobacco mosaic virus RNA enters chloroplasts in vivo.
AB  - Several lines of evidence are presented to allow us to conclude that tobacco
      mosaic virus (TMV) RNA enters the chloroplast in vivo. Chloroplasts were prepared
      from either directly inoculated or systemically infected leaves of tobacco plants
      inoculated with one of several strains of the virus and from uninfected control
      plants. Intact chloroplasts were isolated on Percoll gradients and treated with
      pancreatic RNase and thermolysin to destroy potential TMV virions and RNA on the
      outside or bound to their surfaces. Northern blot analysis of RNA extracted from
      these chloroplasts demonstrated that full-length TMV RNA was present within the
      chloroplasts prepared from both directly inoculated and systemically invaded
      leaves. Only genomic length, but not subgenomic length, RNA was found in the
      chloroplast extracts, indicating a selectivity of the transport of the viral RNA
      into the chloroplast. A temperature-sensitive TMV mutant (Ts 38), in which no
      virions are formed at 35 degrees C, was used to demonstrate that at that
      restrictive temperature viral RNA is detected in the chloroplast, indicating that
      free viral RNA can enter the chloroplast rather than intact virions. To our
      knowledge, the transport of a foreign RNA species into chloroplasts has not been
      reported previously.

PMID- 16578845
TI  - cricklet: A locus regulating a number of adult functions of Drosophila
      melanogaster.
AB  - During a screen for mutations in trans-acting genes regulating yolk protein
      synthesis in Drosophila melanogaster, we have isolated a mutant (cricklet, clt)
      that is defective in yolk protein synthesis, histolysis of the larval fat body,
      vitellogenesis, and synthesis of larval serum protein 2 in the adult, larval
      synthesis occurring normally. Larval serum protein 2 was previously thought to be
      synthesized only in the third-instar larva. We suggest that the clt locus may
      encode a protein essential for mediating the response of adult tissues to
      juvenile hormone.

PMID- 16578846
TI  - EDITORIAL: Old and New Policy Issues at PNAS.

PMID- 16578848
TI  - Activation of protein kinase C by elevation of glucose concentration: Proposal
      for a mechanism in the development of diabetic vascular complications.

PMID- 16578849
TI  - About the proceedings.

PMID- 16578847
TI  - Photoreduction of carbon dioxide by aqueous ferrous ion: An alternative to the
      strongly reducing atmosphere for the chemical origin of life.

PMID- 16578850
TI  - Editor'S note.

PMID- 16578851
TI  - Introduction to colloquium.

PMID- 16578852
TI  - Introduction to frontiers of science.

PMID- 16578853
TI  - Newly elected members and foreign associates of the national academy of sciences
      april 29, 1997.

PMID- 16578854
TI  - Introduction.

PMID- 16578855
TI  - Introduction to german-american frontiers of science.

PMID- 16578856
TI  - Academy honors 15 for major contributions to science.

PMID- 16578857
TI  - Retraction.

PMID- 16578858
TI  - Retraction.

PMID- 16578859
TI  - New members and foreign associates elected to the national academy of sciences on
      may 1, 2001: 72 new members chosen by the academy.
AB  - The Academy has elected 72 new members and 15 foreign associates from 10
      countries in recognition of their distinguished and continuing achievements in
      original research. The election was held during the business session of the 138th
      annual meeting of the Academy. Election to membership in the Academy is
      considered one of the highest honors that can be accorded a U.S. scientist or
      engineer. Foreign associates are non-voting members of the Academy, with
      citizenship outside of the United States.

PMID- 16578860
TI  - Introduction to german-american frontiers of science.

PMID- 16578861
TI  - Introduction to the Japanese-american frontiers of science.

PMID- 16578862
TI  - Introduction to frontiers of science.

PMID- 16578863
TI  - Drainage basins and channel incision on Mars.
AB  - Measurements acquired by the Mars Orbiter Laser Altimeter on board the Mars
      Global Surveyor indicate that large drainage systems on Mars have geomorphic
      characteristics inconsistent with prolonged erosion by surface runoff. We find
      the topography has not evolved to an expected equilibrium terrain form, even in
      areas where runoff incision has been previously interpreted. By analogy with
      terrestrial examples, groundwater sapping may have played an important role in
      the incision. Longitudinally flat floor segments may provide a direct indication
      of lithologic layers in the bedrock, altering subsurface hydrology. However, it
      is unlikely that floor levels are entirely due to inherited structures due to
      their planar cross-cutting relations. These conclusions are based on previously
      unavailable observations, including extensive piece-wise linear longitudinal
      profiles, frequent knickpoints, hanging valleys, and small basin concavity
      exponents.

PMID- 16578864
TI  - Faceting on He crystals.
AB  - It has been predicted by Landau that, ideally at low temperatures, crystals
      should show many different types of facets, i.e., flat smooth faces on their
      surface, but this so-called "devil's staircase" phenomenon has been difficult to
      observe experimentally. In this paper we describe our recent experiments, in
      which altogether 11 different types of facets have been identified on growing
      (3)He crystals at the temperature of 0.55 mK by using a unique low-temperature
      Fabry-Perot interferometer. Previously only 3 types of facets had been seen in
      this system. We have also measured the growth velocities of different facets, and
      our interpretation of the obtained results yields the conclusion that (3)He has
      much stronger coupling of the liquid-solid interface to the crystal lattice than
      has been expected. After an introduction we present a short theoretical
      background about the equilibrium crystal shape and the roughening transitions,
      which is followed by the description of our experimental results and discussion.

PMID- 16578865
TI  - Reaching across the sciences.

PMID- 16578866
TI  - All-optical processing with molecular switches.
AB  - A gradual transition from electrical to optical networks is accompanying the
      rapid progress of telecommunication technology. The urge for enhanced
      transmission capacity and speed is dictating this trend. In fact, large volumes
      of data encoded on optical signals can be transported rapidly over long
      distances. Their propagation along specific routes across a communication network
      is ensured by a combination of optical fibers and optoelectronic switches. It is
      becoming apparent, however, that the interplay between the routing electrical
      stimulations and the traveling optical signals will not be able to support the
      terabit-per-second capacities that will be needed in the near future. Electrical
      inputs cannot handle the immense parallelism potentially possible with optical
      signals. Operating principles to control optical signals with optical signals
      must be developed. Molecular and supramolecular switches are promising candidates
      for the realization of innovative materials for information technology. Binary
      digits can be encoded in their chemical, electrical, or optical inputs and
      outputs to execute specific logic functions. We have developed a simple strategy
      to gate optical signals with optical signals by using a photoactive molecular
      switch. We have demonstrated that NAND, NOR, and NOT operations can be
      implemented exclusively with optical inputs and optical outputs coupling from one
      to three switching elements. Our remarkably simple approach to all-optical
      switching might lead to the development of a new generation of devices for
      digital processing and communication technology.

PMID- 16578867
TI  - Winners don't take all: Characterizing the competition for links on the web.
AB  - As a whole, the World Wide Web displays a striking "rich get richer" behavior,
      with a relatively small number of sites receiving a disproportionately large
      share of hyperlink references and traffic. However, hidden in this skewed global
      distribution, we discover a qualitatively different and considerably less biased
      link distribution among subcategories of pages-for example, among all university
      homepages or all newspaper homepages. Although the connectivity distribution over
      the entire web is close to a pure power law, we find that the distribution within
      specific categories is typically unimodal on a log scale, with the location of
      the mode, and thus the extent of the rich get richer phenomenon, varying across
      different categories. Similar distributions occur in many other naturally
      occurring networks, including research paper citations, movie actor
      collaborations, and United States power grid connections. A simple generative
      model, incorporating a mixture of preferential and uniform attachment, quantifies
      the degree to which the rich nodes grow richer, and how new (and poorly
      connected) nodes can compete. The model accurately accounts for the true
      connectivity distributions of category-specific web pages, the web as a whole,
      and other social networks.

PMID- 16578868
TI  - Two functional equations preserving functional forms.
AB  - Two functional equations are considered that are motivated by three
      considerations: work in utility theory and psychophysics, questions concerning
      when pairs of degree 1 homogeneous functions can be homomorphic and calculating
      their homomorphisms, and the link of the latter questions to quasilinear mean
      values. The first equation is h(sigma(y)x + [1 - sigma(y)]y) = tau(y)h(x) + [1 -
      tau(y)]h(y) (x >= y >= 0), where h maps [0, infinity[into a subset of [0,
      infinity[and is strictly increasing and continuously differentiable; the
      functions sigma and tau map [0, infinity[continuously into [0,1], sigma(y) > 0
      for y > 0 but sigma is not 1 on]0, infinity[. The solutions are fully determined.
      (Recently Zsolt Pales has eliminated the differentiability assumption.) The
      second equation is h[y + f(x - y)] = h(y) + g[h(x) - h(y)] (x >= y >= 0), where h
      maps [0, infinity[onto a subinterval of positive length of [0, infinity[and is
      strictly increasing and twice continuously differentiable, f and g map [0,
      infinity[onto[0, infinity[and are twice differentiable, and either f"(0) ? 0 or
      g"(0) ? 0. The solutions are fully determined under these conditions. When f"(0)
      = g"(0) = 0 and h" is not identically zero, we determine the solutions under the
      added assumption of analyticity. It remains an open problem to find the solutions
      in the latter case under the assumption of only second order differentiability. A
      more general open problem is to eliminate all differentiability conditions for
      the second equation.

PMID- 16578869
TI  - The Pythagorean Theorem: II. The infinite discrete case.
AB  - The study of the Pythagorean Theorem and variants of it as the basic result of
      noncommutative, metric, Euclidean Geometry is continued. The emphasis in the
      present article is the case of infinite discrete dimensionality.

PMID- 16578870
TI  - Clustering of solitons in weakly correlated wavefronts.
AB  - We demonstrate theoretically and experimentally the spontaneous clustering of
      solitons in partially coherent wavefronts during the final stages of pattern
      formation initiated by modulation instability and noise.

PMID- 16578871
TI  - Nanoindentation: Toward the sensing of atomic interactions.
AB  - The mechanical properties of surfaces of layered materials (highly oriented
      pyrolytic graphite, InSe, and GaSe) and single-crystal ionic materials (NaCl,
      KBr, and KCl) have been investigated at the nanometer scale by using
      nanoindentations produced with an atomic force microscope with ultrasharp tips.
      Special attention has been devoted to the elastic response of the materials
      before the onset of plastic yield. A new model based on an equivalent spring
      constant that takes into account the changes in in-plane interactions on
      nanoindentation is proposed. The results of this model are well correlated with
      those obtained by using the Debye model of solid vibrations.

PMID- 16578873
TI  - PNAS gives free online access to developing countries.

PMID- 16578872
TI  - Electronic structure of multiquantum giant vortex states in mesoscopic
      superconducting disks.
AB  - We report self-consistent calculations of the microscopic electronic structure of
      the so-called giant vortex states. These multiquantum vortex states, detected by
      recent magnetization measurements on submicron disks, are qualitatively different
      from the Abrikosov vortices in the bulk. We find that, in addition to multiple
      branches of bound states in the core region, the local tunneling density of
      states exhibits Tomasch oscillations caused by the single-particle interference
      arising from quantum confinement. These features should be directly observable by
      scanning tunneling spectroscopy.

PMID- 16578874
TI  - A simple model of global cascades on random networks.
AB  - The origin of large but rare cascades that are triggered by small initial shocks
      is a phenomenon that manifests itself as diversely as cultural fads, collective
      action, the diffusion of norms and innovations, and cascading failures in
      infrastructure and organizational networks. This paper presents a possible
      explanation of this phenomenon in terms of a sparse, random network of
      interacting agents whose decisions are determined by the actions of their
      neighbors according to a simple threshold rule. Two regimes are identified in
      which the network is susceptible to very large cascades-herein called global
      cascades-that occur very rarely. When cascade propagation is limited by the
      connectivity of the network, a power law distribution of cascade sizes is
      observed, analogous to the cluster size distribution in standard percolation
      theory and avalanches in self-organized criticality. But when the network is
      highly connected, cascade propagation is limited instead by the local stability
      of the nodes themselves, and the size distribution of cascades is bimodal,
      implying a more extreme kind of instability that is correspondingly harder to
      anticipate. In the first regime, where the distribution of network neighbors is
      highly skewed, it is found that the most connected nodes are far more likely than
      average nodes to trigger cascades, but not in the second regime. Finally, it is
      shown that heterogeneity plays an ambiguous role in determining a system's
      stability: increasingly heterogeneous thresholds make the system more vulnerable
      to global cascades; but an increasingly heterogeneous degree distribution makes
      it less vulnerable.

PMID- 16578875
TI  - A model of a turbulent boundary layer with a nonzero pressure gradient.
AB  - According to a model of the turbulent boundary layer that we propose, in the
      absence of external turbulence the intermediate region between the viscous
      sublayer and the external flow consists of two sharply separated self-similar
      structures. The velocity distribution in these structures is described by two
      different scaling laws. The mean velocity u in the region adjacent to the viscous
      sublayer is described by the previously obtained Reynolds-number-dependent
      scaling law Phi = u / u(*) = Aeta(alpha), A = 1/?3 In ReLambda + 5/2, alpha = 3/2
      in ReLambda eta = u(*)y/v. (Here u(*) is the dynamic or friction velocity, y is
      the distance from the wall, nu the kinetic viscosity of the fluid, and the
      Reynolds number ReLambda is well defined by the data.) In the region adjacent to
      the external flow, the scaling law is different: Phi = Beta(beta). The power beta
      for zero-pressure-gradient boundary layers was found by processing various
      experimental data and is close (with some scatter) to 0.2. We show here that for
      nonzero-pressure-gradient boundary layers, the power beta is larger than 0.2 in
      the case of an adverse pressure gradient and less than 0.2 for a favorable
      pressure gradient. Similarity analysis suggests that both the coefficient Beta
      and the power beta depend on ReLambda and on a new dimensionless parameter P
      proportional to the pressure gradient. Recent experimental data of Perry,
      Marusic, and Jones were analyzed, and the results are in agreement with the model
      we propose.

PMID- 16578876
TI  - Simulating materials failure by using up to one billion atoms and the world's
      fastest computer: Brittle fracture.
AB  - We describe the first of two large-scale atomic simulation projects on materials
      failure performed on the 12-teraflop ASCI (Accelerated Strategic Computing
      Initiative) White computer at Lawrence Livermore National Laboratory. This is a
      multimillion-atom simulation study of crack propagation in rapid brittle fracture
      where the cracks travel faster than the speed of sound. Our finding centers on a
      bilayer solid that behaves under large strain like an interface crack between a
      soft (linear) material and a stiff (nonlinear) material. We verify that the crack
      behavior is dominated by the local (nonlinear) wave speeds, which can be in
      excess of the conventional sound speeds of a solid.

PMID- 16578877
TI  - Simulating materials failure by using up to one billion atoms and the world's
      fastest computer: Work-hardening.
AB  - We describe the second of two large-scale atomic simulation projects on materials
      failure performed on the 12-teraflop ASCI (Accelerated Strategic Computing
      Initiative) White computer at the Lawrence Livermore National Laboratory. This
      investigation simulates ductile failure by using more than one billion atoms
      where the true complexity of the creation and interaction of hundreds of
      dislocations are revealed.

PMID- 16578878
TI  - PNAS publishes daily online.

PMID- 16578879
TI  - Very high growth rate chemical vapor deposition of single-crystal diamond.
AB  - Diamond possesses extraordinary material properties, a result that has given rise
      to a broad range of scientific and technological applications. This study reports
      the successful production of high-quality single-crystal diamond with microwave
      plasma chemical vapor deposition (MPCVD) techniques. The diamond single crystals
      have smooth, transparent surfaces and other characteristics identical to that of
      high-pressure, high-temperature synthetic diamond. In addition, the crystals can
      be produced at growth rates from 50 to 150 mum/h, which is up to 2 orders of
      magnitude higher than standard processes for making polycrystalline MPCVD
      diamond. This high-quality single-crystal MPCVD diamond may find numerous
      applications in electronic devices as high-strength windows and in a new
      generation of high-pressure instruments requiring large single-crystal anvils.

PMID- 16578880
TI  - Efficiency wages in an experimental labor market.
AB  - There has been recent experimental support for efficiency wage theories of the
      labor market. This short paper initiates the larger process of evaluating the
      boundary conditions of the gift- exchange phenomenon. In particular, we will see
      whether behavior consistent with the fair wage-effort hypothesis can emerge and
      be sustained under conditions in which there is (i) a nontrivial marginal cost to
      providing effort and (ii) increased social distance between subject and
      experimenter.

PMID- 16578882
TI  - The cost of antibiotic treatment for priority infectious syndromes in Paraguay,
      2004.

PMID- 16578883
TI  - Methods for measuring health inequalities (Part III).

PMID- 16578881
TI  - Health Metrics Network: a global partnership to improve access to information for
      health care practitioners and policy-makers.

PMID- 16578884
TI  - Tune into your ratio(s).

PMID- 16578885
TI  - Sweet substitutes. An update.

PMID- 16578886
TI  - Diabetes basics. Sexual wellness.

PMID- 16578887
TI  - Eating across America. Southern cooking.

PMID- 16578888
TI  - Preventing colorectal cancer.

PMID- 16578889
TI  - Functional foods. Make every calorie count.

PMID- 16578890
TI  - For parents. Bodybuilding supplements. Are any of them safe?

PMID- 16578891
TI  - Diabetes quiz. How much do you know about chronic kidney disease?

PMID- 16578892
TI  - Supermarket smarts. Rice and rice mixes.

PMID- 16578894
TI  - Diabetes resources. Exercising at home.

PMID- 16578893
TI  - Pregnancy with diabetes. A doable challenge.

PMID- 16578895
TI  - Injectable drug approved for osteoporosis.

PMID- 16578897
TI  - Sunlight exposure risk outweighs vit. D benefit.

PMID- 16578896
TI  - Low-fat diabetes: anatomy of a misleading study. More questions, few answers;
      study says health benefits of low-fat diet are less than expected.

PMID- 16578898
TI  - Is it safe to eat soy? The debate continues: recent tests on monkeys prove soy to
      be beneficial, but more clinical trials are needed.

PMID- 16578899
TI  - Thyroid cancer benefits from post-surgery HT.

PMID- 16578900
TI  - Effects of some meds could lead to mistaken dementia diagnosis. Dementia is
      sometimes diagnosed where there is none. Be sure to tell your doctor about ALL
      your meds.

PMID- 16578901
TI  - New tests for AD.

PMID- 16578902
TI  - I have read about a new study that showed antidepressants can increase the risk
      of abdominal bleeding. I'm currently taking Prozac, and my husband takes Zoloft.
      Should we worry?

PMID- 16578903
TI  - Negative photoconductivity and memory effects of germanium nanocrystals embedded
      in HfO2 dielectric.
AB  - A metal-insulator-semiconductor (MIS) structure containing an HfO2/SiO2 stack
      tunnel layer, isolated Germanium (Ge) nanocrystals, and an HfO2 capping layer,
      was obtained by an electron-beam evaporation method. A high-resolution
      transmission electron microscopy (HRTEM) study revealed that uniform and
      pronounced Ge nanocrystals had formed after annealing. Raman spectroscopy
      provided evidence for the formation of Ge-Ge bonds and the optimal annealing
      temperature for the crystallization ratio of the Ge. The electric properties of
      the MIS structure were characterized by capacitance-voltage (C-V) and current
      voltage (I-V) measurements at room temperature. Negative photoconductivity was
      observed when the structure was under a forward bias, which screened the bias
      voltage, resulting in a decrease in the current at a given voltage and a negative
      shift in flat band voltage. A relatively high stored charge density of 3.27 x
      10(12) cm 2 was also achieved.

PMID- 16578904
TI  - Microbial biomass, P-nutrition, and enzymatic activities of wheat soil in
      response to phosphorus enriched organic and inorganic manures.
AB  - Compost was prepared from wheat straw enriched with Rajasthan rock phosphate and
      Aspergillus awamori. The resulting phospho-compost along with phosphorus enriched
      FYM, mineral fertilizer (rock phosphate) and super phosphate were evaluated for
      their individual contribution in improving organic matter status, P availability,
      and enzymatic activities of soil under wheat crop grown in a micro plot. The
      results showed that total organic carbon, nitrogen, microbial biomass, and humus
      content (an index of organic matter status of soil) of soil was highest when farm
      yard manure (FYM) after its enrichment with 12.5% rock phosphate was applied.
      Microbial enriched phospho-compost was the product yielding highest soil
      available phosphorus, phosphorus uptake, urease, and cellulase activities.
      However, FYM amended with 25% rock phosphate resulted in the greatest enhancement
      of beta- glucosidase. Measured parameters indicated a sure improvement of
      chemical and biological activities of soil after the application of phosphorus
      enriched organic amendments compared to the commercial fertilizer commonly used
      by the Indian farmers.

PMID- 16578906
TI  - Methodological reflections on the evaluation of health programs and services.

PMID- 16578905
TI  - Hurricanes Katrina and Rita.

PMID- 16578907
TI  - Summary of indicators most used for the measurement of the health inequalities.

PMID- 16578908
TI  - Safety of IVF under anticoagulant therapy in patients at risk for thrombo-embolic
      events.
AB  - The objective of this study was to assess the safety of induction of ovulation
      and oocyte retrieval in patients at risk of thrombosis, necessitating treatment
      with anticoagulants. Twenty-four patients considered as high risk for a
      thromboembolic event underwent 73 IVF cycles and 68 oocyte retrieval procedures,
      and were treated concomitantly with anticoagulation therapy (low molecular weight
      heparin; LMWH). A subgroup of five patients considered at especially high risk
      for thrombosis was isolated. These patients were prepared for oocyte retrieval
      using a controlled spontaneous cycle. All these patients were programmed
      exclusively for surrogacy. Nineteen women underwent 49 cycles of ovulation
      induction with gonadotrophins. The average peak oestradiol concentration was 1791
      +/- 1420 pg/ml with an average of 13.5 +/- 8.4 oocytes retrieved in each cycle.
      The five patients from the very high risk group underwent 24 cycles: the average
      peak oestradiol concentration was 163 +/- 98 pg/ml. In 18, an egg was retrieved
      and in 14, fertilization was achieved. No bleeding or thromboembolic
      complications were noted during treatment of both groups of patients. It is
      concluded that during induction of ovulation in patients at risk for thrombosis,
      the introduction of LMWH as a cycle protective treatment was not associated with
      any medical complication. The use of a controlled spontaneous cycle with LMWH is
      suggested in very high risk patients.

PMID- 16578909
TI  - Integrative Tumor Board: pediatric synovial sarcoma.

PMID- 16578911
TI  - Vioxx doctors wooed by Merck are now its foes.

PMID- 16578912
TI  - Blood-substitute study is criticized by U.S. agency.

PMID- 16578913
TI  - Abortion issue moves to states: shift on federal bench spurs governors,
      legislators to battle Roe.

PMID- 16578914
TI  - Gender gene implicated in Parkinson's disease.

PMID- 16578915
TI  - Amyloid-beta antibody to restore cholinergic function?

PMID- 16578916
TI  - Fever turns up the heat on GABA(A) receptors.

PMID- 16578918
TI  - Immune cells from blood attack Alzheimer's plaques.

PMID- 16578917
TI  - The Scientific Misconduct Questionnaire--Revised (SMQ-R): validation and
      psychometric testing.
AB  - PURPOSE: The overall purposes of this article are to report the development of a
      survey instrument, Scientific Misconduct Questionnaire-Revised (SMQ-R) that
      elicits the perceptions of research coordinators managing clinical trials about
      the various aspects of scientific misconduct and to present psychometric analyses
      for the SMQ-R. METHODS: A panel of five researchers and research coordinators
      reviewed the original SMQ (Rankin and Esteeves, 1997) and suggested an additional
      42 items based on the review of the literature and their own experiences in
      research. The SMQ-Revised (SMQ-R) consists of 68 closed-choice items in six
      sections and one section with 12 open-ended questions. The SMQ-R was sent to 5302
      persons who were members of the Association for Clinical Research Professionals
      (ACRP) or subscribers to Research Practitioner, published by the Center for
      Clinical Research Practice (CCRP). FINDINGS: Internal consistency of subscales
      was assessed with Cronbach's alpha and ranged from .83 to .84. Confirmatory
      factor analysis was used to test construct validity of the instrument subscales.
      The factor structure was assessed with the principal factors method, using the
      squared multiple correlations as initial communality estimates followed by
      varimax (orthogonal) or biquartimax (oblique) rotations. Analyses revealed five
      distinct factors among three subscales. Construct validity for the SMQ-R was also
      assessed by testing hypothesized relationships using the known groups approach.
      CONCLUSION: The current effort demonstrated the usefulness of the SMQ-R in
      obtaining information from a national sample of experienced research coordinators
      about their perceptions of the prevalence of different types of scientific
      misconduct and of factors that influence the occurrence of misconduct. The
      psychometric evaluation of the SMQ-R suggests good internal consistency for most
      subscales and suggests adequate construct validity of the instrument as a whole.
      The analyses also suggest that further refinement of the instrument for future
      studies is warranted.

PMID- 16578919
TI  - Potassium channels have a key role in neurodegeneration.

PMID- 16578920
TI  - An appetite for learning.

PMID- 16578921
TI  - Drug shows promise for treatment of Alzheimer's disease.

PMID- 16578922
TI  - Assessing commercial feasibility: a practical and ethical prerequisite for human
      clinical testing.
AB  - This article proposes that an assessment of commercial feasibility should be
      integrated as a prerequisite for human clinical testing to improve the quality
      and relevance of materials being investigated, as an ethical aspect for human
      subject protection, and as a means of improving accountability where clinical
      development is funded on promises of successful translational research. A
      commercial feasibility analysis is not currently required to justify human
      clinical testing, but is assumed to have been conducted by industry participants,
      and use of public funds for clinical trials should be defensible in the same
      manner. Plant-made vaccines (PMVs) are offered in this discussion as a model for
      evaluating the relevance of commercial feasibility before human clinical testing.
      PMVs have been proposed as a potential solution for global health, based on a
      vision of immunizing the world against many infectious diseases. Such a vision
      depends on translating current knowledge in plant science and immunology into a
      potent vaccine that can be readily manufactured and distributed to those in need.
      But new biologics such as PMVs may fail to be manufactured due to financial or
      logistical reasons--particularly for orphan diseases without sufficient revenue
      incentive for industry investment--regardless of the effectiveness which might be
      demonstrated in human clinical testing. Moreover, all potential instruments of
      global health depend on translational agents well beyond the lab in order to
      reach those in need. A model compromising five criteria for commercial
      feasibility is suggested for inclusion by regulators and ethics review boards as
      part of the review process prior to approval of human clinical testing. Use of
      this model may help to facilitate safe and appropriate translational research and
      bring more immediate benefits to those in need.

PMID- 16578923
TI  - Rating methodological quality: toward improved assessment and investigation.
AB  - Assessing methodological quality is considered essential in deciding what
      investigations to include in research syntheses and in detecting potential
      sources of bias in meta-analytic results. Quality assessment is also useful in
      characterizing the strengths and limitations of the research in an area of study.
      Although numerous instruments to measure research quality have been developed,
      they have lacked empirically-supported components. In addition, different summary
      quality scales have yielded different findings when they were used to weight
      treatment effect estimates for the same body of research. Suggestions for
      developing improved quality instruments include: distinguishing distinct domains
      of quality, such as internal validity, external validity, the completeness of the
      study report, and adherence to ethical practices; focusing on individual aspects,
      rather than domains of quality; and focusing on empirically-verified criteria.
      Other ways to facilitate the constructive use of quality assessment are to
      improve and standardize the reporting of research investigations, so that the
      quality of studies can be more equitably and thoroughly compared, and to identify
      optimal methods for incorporating study quality ratings into meta-analyses.

PMID- 16578924
TI  - The IRB paradox: could the protectors also encourage deceit?
AB  - The efforts of some institutional review boards (IRBs) to exercise what is viewed
      as appropriate oversight may contribute to deceit on the part of investigators
      who feel unjustly treated. An organizational justice paradigm provides a useful
      context for exploring why certain IRB behaviors may lead investigators to believe
      that they have not received fair treatment. These feelings may, in turn, lead to
      intentional deception by investigators that IRBs will rarely detect.
      Paradoxically, excessive protective zeal by IRBs may actually encourage
      misconduct by some investigators. The authors contend that, by fostering a
      climate in which investigators perceive that they receive fair and unbiased
      treatment, IRBs optimize the likelihood of collegial compliance with appropriate
      participant protections.

PMID- 16578925
TI  - Putting long-range mapping in reach.
AB  - A technique for performing PCR on extremely large DNA molecules offers
      researchers the ability to generate accurate multi-marker haplotypes for large
      numbers of patients--even with loci arrayed across entire human chromosomes.

PMID- 16578926
TI  - Increasingly informed consent: discussing distinct aspects of psychotherapy at
      different points in time.
AB  - Psychologists are ethically obligated to obtain informed consent to psychotherapy
      "as early as is feasible" (American Psychological Association, 2002, p.1072).
      However, the range of topics to be addressed includes both information that may
      be immediately and uniformly applicable to most clients via policy or rule, as
      well as information that is not immediately presentable because it varies widely
      across clients or emerges over time. In this study, licensed psychologists were
      surveyed regarding the earliest feasible point at which they could provide
      information regarding specific aspects of psychotherapy. Results indicate that,
      although psychologists believe that they are capable of presenting some
      information, such as payment and confidentiality policies, at the outset, they
      believe that a discussion of more substantive issues, such as psychotherapy
      duration, goals, orientation, and activities, can take place only after some
      therapy has transpired. Implications are discussed regarding the process and
      event models of informed consent.

PMID- 16578927
TI  - Bioluminescent quantum dots.
AB  - Bioluminescence is widely used for in vivo imaging of nude mice. By conjugating
      luciferase protein to quantum dots, bioluminescence resonance energy transfer
      (BRET) turns these useful fluorophores into a new class of bioluminescent probe.

PMID- 16578928
TI  - Harnessing a tiny hairy beast.
AB  - With the goal of using the ciliate Tetrahymena thermophila for biotechnology
      applications-as a heterologous protein expression system-researchers have
      identified a copper-inducible and repressible promoter.

PMID- 16578929
TI  - Improving evolution.
AB  - By combining elements of protein engineering and directed evolution, researchers
      open the door to creating enzymes with diverse catalytic functions in a protein
      scaffold of their choice.

PMID- 16578930
TI  - Hands-off protein crystallography.

PMID- 16578931
TI  - Coke and chips--a winning combination?
AB  - An aptamer-based electronic sensor for the detection of cocaine demonstrates the
      capabilities of a sensitive and generalizable new platform for small-molecule
      recognition.

PMID- 16578932
TI  - Recent developments in the law.

PMID- 16578933
TI  - Re: Classic chronic renal failure: hyperkalemia and hypocalcemia.

PMID- 16578934
TI  - Health and nutrition education in primary schools in Crete: 10 years follow-up of
      serum lipids, physical activity and macronutrient intake.
AB  - The current study is a 4-year follow-up after the 6-year-long health and
      nutrition intervention programme applied in the primary schools of Crete. The aim
      of the current work was to identify whether the benefits obtained in certain
      health indices at the end of the intervention period were also present 4 years
      later. From a representative population of 441 pupils (250 from the intervention
      schools and 191 from the control schools), biochemical, dietary and physical
      activity data were obtained at baseline, at the end of the intervention period
      and after intervention (academic years 1992- 1993, 1997-1998 and 2001-2002,
      respectively). The findings of the current study revealed that the favourable
      changes in serum lipids observed at the end of the intervention period were
      maintained from baseline to after intervention for total cholesterol (-24-3 (SE
      1.65) v. -9.70 (SE 2.03) mg/dl; P = 0-001), LDL-cholesterol(-18.6 (SE 1-41) v. 
      2.49 (SE 1.75) mg/dl; P < 0-001), HDL-cholesterol (-8-34 (SE 0.75) v. -9-60 (SE 1
      10) mg/dl; P = 0-014) and total cholesterol :HDL-cholesterol ratio (0.31 (SE
      0.06) v. 0.04 (SE 0.05); P = 0001). Similar favourable changes for the
      intervention group were observed in leisure-time physical activities (38.3 (SE 11
      7) v. -13.2 (SE 10.9) min/week; P = 0.038) and BMI (6-05 (SE 0.18) v. 6.67 (SE 0
      21) kg/m(2);P = 0.014), whereas no changes were observed in the fitness and
      dietary indices examined. The findings of the current study are encouraging,
      indicating maintenance of the favourable changes observed in serum lipids, BMI
      and physical activity 4 years after the programme had ended.

PMID- 16578935
TI  - Dietary risk factors for the emergence of type 1 diabetes-related autoantibodies
      in 21/2 year-old Swedish children.
AB  - We studied dietary risk factors by analysing a questionnaire administered at
      birth, 1 year and 2(1/2) years of age, as well as the level of glutamic acid
      decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies (IA
      2A), in 7208 2(1/2)-year-old children from the All Babies in Southeast Sweden
      cohort, using the 95th percentile cut-off for autoantibodies to identify children
      at risk of type 1 diabetes. A total of 657 children had either IA-2A (n 360) or
      GADA (n 335), and thirty-eight children had both GADA and IA-2A. In univariate
      analysis, male gender and maternal coeliac disease implied a risk of possessing
      IA-2A. Maternal type 2 diabetes, a high consumption of fresh cows milk at the age
      of 1 year and a late introduction of gluten were associated with a risk of GADA.
      Early cessation of breast-feeding (< 2 months of age) was associated with a risk
      of the simultaneous occurrence of both IA-2A and GADA. In logistic regression
      analysis, a high consumption of milk at the age of I year (odds ratio
      2.6)represented a risk for GADA, and maternal coeliac disease (odds ratio 2.9)
      represented a risk for IA-2A. The combination of an early introduction of cows
      milk formula and a late introduction of gluten-containing food gave an odds ratio
      of 6.0 for positivity for at least one autoantibody at 1 and 21 years of age. The
      induction of autoantibodies by the age of 2(1/2) years has a male preponderance
      and is more common in children with maternal type 2 diabetes or maternal coeliac
      disease. Dietary risk factors for the induction of beta-cell autoantibodies in 21
      year-old children are a short duration of breast-feeding, an early introduction
      of cows milk formula and a late introduction of gluten, as well as a high
      consumption of milk at the age of I year.

PMID- 16578936
TI  - Joint Commission names 2004 Ernest A. Codman Award Winners.

PMID- 16578937
TI  - Clarification on practitioner leave of absence or deployment at
      reappointment/reprivileging.

PMID- 16578938
TI  - New accreditation participation requirement for all programs.

PMID- 16578939
TI  - Official Joint Commission e-mails to accredited organizations.

PMID- 16578940
TI  - Generating a taxonomy of regulatory responses to emerging issues in biomedicine.
AB  - In the biomedical field, calls for the generation of new regulations or for the
      amendment of existing regulations often follow the emergence of apparently new
      research practices (such as embryonic stem cell research), clinical practices
      (such as facial transplantation) and entities (such as Avian Influenza/'Bird
      Flu'). Calls for regulatory responses also arise as a result of controversies
      which bring to light longstanding practices, such as the call for increased
      regulation of human tissue collections that followed the discovery of
      unauthorised post-mortem organ retention. Whilst it seems obvious that new
      regulations should only be generated if existing regulations are inadequate (a
      practice referred to in this paper as 'regulatory syncretism'), this does not
      always occur in practice. This paper examines the conceptual steps involved in
      generating regulatory responses to emerging phenomena. Two decision points are
      identified. First, a stance is taken as to whether the emerging phenomenon raises
      unique ethical or legal issues (exceptionalism versus non-exceptionalism).
      Second, the decision is made as to whether new regulation should be generated
      only for truly unique phenomena (syncretism versus asyncretism). It is argued
      here that it is important to make a careful assessment of novelty, followed by a
      reflective and deliberative choice of regulatory syncretism or asyncretism, since
      each type of regulatory response has advantages which need to be harnessed and
      disadvantages which need to be managed--something that can only occur if
      regulators are attentive to the choices they are making.

PMID- 16578942
TI  - An economic theory of patient decision-making.
AB  - Patient autonomy, as exercised in the informed consent process, is a central
      concern in bioethics. The typical bioethicist's analysis of autonomy centers on
      decisional capacity--finding the line between autonomy and its absence. This
      approach leaves unexplored the structure of reasoning behind patient treatment
      decisions. To counter that approach, we present a microeconomic theory of patient
      decision-making regarding the acceptable level of medical treatment from the
      patient's perspective. We show that a rational patient's desired treatment level
      typically departs from the level yielding an absence of symptoms, the level we
      call ideal. This microeconomic theory demonstrates why patients have good reason
      not to pursue treatment to the point of absence of physical symptoms. We defend
      our view against possible objections that it is unrealistic and that it fails to
      adequately consider harm a patient may suffer by curtailing treatment. Our
      analysis is fruitful in various ways. It shows why decisions often considered
      unreasonable might be fully reasonable. It offers a theoretical account of how
      physician misinformation may adversely affect a patient's decision. It shows how
      billing costs influence patient decision-making. It indicates that health care
      professionals' beliefs about the 'unreasonable' attitudes of patients might often
      be wrong. It provides a better understanding of patient rationality that should
      help to ensure fuller information as well as increased respect for patient
      decision-making.

PMID- 16578941
TI  - Compromised ethical principles in randomised clinical trials of distant,
      intercessory prayer.
AB  - The effects of distant, intercessory prayer on health outcomes have been studied
      in a range of randomised, blinded clinical trials. However, while seeking the
      evidentiary status accorded this 'gold standard' methodology, many prayer studies
      fall short of the requirements of the World Medical Association's Declaration of
      Helsinki for the ethical conduct of trials involving human subjects. Within a
      sample of 15 such studies published in the medical literature, many were found to
      have ignored or waived key ethical precepts, including adequate standards of
      care, patient confidentiality and informed consent. Prayer was considered in most
      studies to pose negligible or no risk to subjects, despite the fact that no clear
      mechanism of action nor any safety monitoring procedures were described. As a
      result, many studies did not meet basic ethical standards required of clinical
      trials of biophysical interventions, making application of their results
      ethically problematic. If investigators wish their data to adequately inform the
      use or rejection of intercessory prayer to improve health, these shortcomings
      should be addressed in future studies.

PMID- 16578943
TI  - Exploring the concept of genetic discrimination.
AB  - The issue of genetic discrimination has attracted growing attention and has been
      the focus of a recent major Australian inquiry. It is, however, a complex and
      loaded notion, open to interpretation. This paper explores the concept of genetic
      discrimination in both its theoretical and practical dimensions. It examines its
      conceptual underpinnings, how it is understood, and how this understanding fits
      within the legal framework of disability discrimination. The paper also examines
      the phenomenon in practice, including the 'fear factor' and the resulting
      implications for the development of regulatory policy. The paper argues that we
      need to be discerning in our interpretation of this term, and differentiate
      between discriminatory conduct which is legal and illegal. Further, it is argued
      that a concerted societal response to the 'problem' of genetic discrimination is
      needed involving targeted legal reforms as well as broader non-legal strategies.

PMID- 16578944
TI  - In that case.

PMID- 16578945
TI  - In that case: response.

PMID- 16578946
TI  - In that case: response.

PMID- 16578947
TI  - In that case: response.

PMID- 16578948
TI  - Correction to "The new Joint Commission accreditation process" chapter.

PMID- 16578949
TI  - Administrative review process for adjudicating initial disability claims. Final
      rule.
AB  - The Social Security Administration is committed to providing the high quality of
      service the American people expect and deserve. In light of the significant
      growth in the number of disability claims and the increased complexity of those
      claims, the need to make substantial changes in our disability determination
      process has become urgent. We are publishing a final rule that amends our
      administrative review process for applications for benefits that are based on
      whether you are disabled under title II of the Social Security Act (the Act), or
      applications for supplemental security income (SSI) payments that are based on
      whether you are disabled or blind under title XVI of the Act. We expect that this
      final rule will improve the accuracy, consistency, and timeliness of decision
      making throughout the disability determination process.

PMID- 16578950
TI  - Reciprocity, justice, and disability.

PMID- 16578951
TI  - Justice through trust: disability and the "outlier problem" in social contract
      theory.

PMID- 16578952
TI  - Causing disabled people to exist and causing people to be disabled.

PMID- 16578953
TI  - At the margins of moral personhood.

PMID- 16578954
TI  - The nonidentity problem, disability, and the role morality of prospective
      parents.

PMID- 16578955
TI  - Invisible disability.

PMID- 16578957
TI  - [Taking the difference of colorectal cancer surgical procedures into
      consideration].

PMID- 16578956
TI  - Rx: professional integrity (prn).

PMID- 16578958
TI  - New accreditation participation requirement regarding organizations' adherence to
      quality report approved for all programs.

PMID- 16578959
TI  - Revisions to the "Do not use abbreviations" requirement.

PMID- 16578960
TI  - Changes to definition of reviewable sentinel events.

PMID- 16578961
TI  - [Role of osteoclasts in bone destruction in rheumatoid arthritis].

PMID- 16578962
TI  - [Role of cell adhesion molecules in wound healing].

PMID- 16578963
TI  - [Gastrointestinal complications of collagen vascular diseases].

PMID- 16578964
TI  - [Case of protein-losing gastroenteropathy associated with scleroderma in which
      central serous chorioretinopathy developed].
AB  - A 44-year-old woman noticed edema of the lower limbs in May 1999 and visited our
      hospital in September 1999 to undergo further examination. On admission, severe
      hypoalbuminemia (1.9 g/dl) was detected with a negative urinary protein level.
      Protein leakage into the gastrointestinal tract and deposition of immune complex
      in the colonic mucosa were shown by the fluorescent antibody method. In addition,
      anti-centromere antibody, sclerodactyly, and findings indicative of histological
      sclerotic changes on a skin biopsy were observed. These findings supported a
      diagnosis of protein-losing gastroenteropathy complicated by scleroderma.
      Administration of oral corticosteroids was begun one month after admission and
      the patient experienced diminished visual acuity immediately after steroid pulse
      therapy in November. Central serous chorioretinopathy (CSC) was diagnosed at the
      Department of Ophthalmology of our hospital, and the administration of
      corticosteroids was suspected as a possible cause of CSC. Considering the
      severity of hypoproteinemia, the corticosteroid treatment was continued despite
      corticosteroids being strogly suspected as the primary cause of CSC. A complete
      disappearance of CSC was achieved in 30 days after the onset of symptoms despite
      continuation of the steroid therapy, and her serum albumin and complement levels
      both normalized. We concluded that damage to the retinal pigment epithelium
      secondary to the vascular lesion at the choroidal level plays a causative role in
      CSC. In the present case, the findings suggested that the deposition of immune
      complex in choroidal tissues as well as the gastrointestinal tract caused
      hyperpermeability of choroidal vessels and led to the development of CSC.

PMID- 16578965
TI  - [Antiendothelial cell antibodies and their relation to pulmonary hypertension in
      connective tissue diseases].

PMID- 16578966
TI  - [Inhibitory effect of human saliva on HIV-1 infectivity].
AB  - Human saliva is known to decrease human immunodeficiency virus type 1 (HIV-1)
      infectivity in vitro. The purpose of this study was to confirm these findings and
      to explore the mechanism of action of saliva. Whole saliva from seronegative
      donors was incubated with HIV-1IIIB chronically infected MOLT 4 cells (MOLT 4/HIV
      1IIIB cells) or cell-free HIV-1IIIB or KMT strains. We monitored viral
      infectivity by using MAGI/CCR5 cells. Whole saliva with Na levels less than 20
      mEq/l rapidly damaged MOLT 4/HIV-1IIIB cells, thereby HIV infection to MAGI/CCR5
      cells by MOLT 4/HIV-1IIIB cells was nearly abolished. On the contrary, in the
      cace of whole saliva with Na levels more than 23 mEq/l which damaged few cells,
      cell-to-cell transmission of HIV-1IIIB was prevented by more than 50%. The
      infectivity of cell-free HIV-1IIIB to MAGI/CCR5 cells was abolished after
      incubating and filtering the HIV with whole saliva. Depletion of secretory
      leukocyte protease inhibitor (SLPI) from whole saliva resulted in a 11-28%
      decrease in the anti HIV-1KMT activity of saliva. Preincubation of host cells
      with whole saliva led to an enhancement of the HIV infection rather than
      inhibition. Whole saliva had no effect on the expression level of the cellular
      receptors (CD4, CXCR4 and CCR5). These results suggest that the inhibitory effect
      of whole saliva on HIV-1 infectivity is directly linked to the virus itself
      rather than on the host cell. Moreover, the physical entrapment of cell-free HIV
      1 by whole saliva seems to have major salivaly defence mechanisms against HIV-1
      infection through the oral cavity.

PMID- 16578967
TI  - [Marginal zone lymphoma associated with Sjogren's syndrome and hepatitis C virus
      infection].
AB  - A 64-year-old female was admitted in May 1997, because of salivary gland
      swelling. Histology of the right parotid gland revealed malignant lymphoma,
      diffuse medium-sized B-cell type, and she was treated with local radiotherapy and
      chemotherapy. She was rehospitalized in April 1998, because of recurrence of
      lymphoma in the stomach and the sigmoid colon. She had splenomegaly and
      lymphadenopathy (neck and inguinal). Laboratory findings revealed marked
      elevation of rheumatoid factor and RNA of hepatitis C virus. A diagnosis of
      Sjogren's syndrome was made by dryness and the histological findings of labial
      biopsy. Marginal zone B-cell lymphoma mainly consisted of centrocyte-like cells
      and lymphoepithelial lesions, and CD 20 and IgM-kappa were positive with
      immunohistochemical staining. Lymphoma involved the gut and spleen. We discuss
      the correlation of malignant lymphoma with Sjogren's syndrome and HCV infection.

PMID- 16578968
TI  - [Case of fulminant mixed cryoglobulinemia developing after atrial myxoma
      resection].
AB  - A 63-year-old man, with a 13-year history of asymptomatic proteinuria, was
      diagnosed with left atrial myxoma at the onset of heart failure. After resection
      of the tumor by hypothermal surgery, the patient developed fever, renal failure
      and skin rash. The diagnosis was type II mixed cryoglobulinemia accompanied by an
      IgMlambda clone with high titers of rheumatoid factor activity and polyclonal
      IgG. Treatment with high doses of steroids and plasmapheresis was ineffective,
      and the patient died of colon necrosis due to thrombotic occlusion in the supra
      mesenteric arteries. Although the patient had suffered from sporadic Raynaud's
      phenomenon and purpura of the lower extremities from the age of 60 years,
      cryoglobulinemia was not suspected before surgery because of the atrial myxoma.
      Thus, we suggest that it is important to perform laboratory tests for
      cryoproteins before hypothermal surgery.

PMID- 16578969
TI  - [B cell signal transduction and autoimmunity].

PMID- 16578970
TI  - [Case of eosinophilic fasciitis with change of serum Th 1/Th 2 cytokine level
      which correlated with disease activity].
AB  - A 25-year-old female who had right knee and ankle joint swelling with arthralgia
      in July 1999, was diagnosed as having eosinophilic fasciitis (EF) based on
      typical skin sign and the result of muscle biopsy. Treatment was started with 20
      mg of oral prednisolone per day. Her symptoms had subsided but they later
      recurred as the prednisolone dose was gradually tapered. We measured her serum
      cytokine levels during the course. Her serum IFN-gamma increased and IL-4
      decreased after the treatment compared with those levels prior to treatment. And
      the cytokine levels reverted to pre-treatment status when she had a relapse. The
      cytokine balance seems to play some role in the etiology of EF.

PMID- 16578972
TI  - [Case of subcutaneous and mesenteric acute panniculitis with Sjogren's syndrome].
AB  - We report a case of a 27-year-old Japanese female with Sjogren's syndrome (SS),
      who suffered from several episodes of subcutaneous and mesenteric panniculitis
      with a recurrence within one year. After a history of fever and skin rash, the
      patient underwent surgery at a local hospital with a diagnosis of acute
      appendicitis complicated with an ileocecal abscess. She was also diagnosed as
      having SS. After the operation, the fever and skin rash persisted. She was
      treated with prednisolone (PSL), and her symptoms resolved. A recurrent bout of
      abdominal pain with fever, annular erythema on the trunk and a nodular
      erythematous rash on the lower extremities occurred six months after the
      operation. A skin biopsy from the lower extremities showed findings that were
      compatible with panniculitis. Abdominal computer tomography (CT) showed a diffuse
      swelling with soft tissue density in the intestinal mesenterium and para aortic
      area. A retrospective examination of the operative specimen obtained from the
      local hospital revealed centrilobular infiltration of neutrophils in the
      mesenteric adipose tissue with fat necrosis, which is compatible with mesenteric
      panniculitis. Twenty mg/day of PSL was successful in treating the systemic
      panniculitis, and the abnormal diffuse soft tissue density on the abdominal CT
      disappeared after three weeks of PSL administration. Systemic panniculitis is a
      rare complication in SS, and the pathogenesis is unclear.

PMID- 16578971
TI  - [Case of dermatomyositis complicated with massive pleural effusion that preceded
      the myopathy].
AB  - A 36-year-old man was admitted to a hospital with complaints of fever,
      polyarthralgia and dyspnea. Erythema was observed on his face, extensor surface
      of the fingers and extremities, and a chest X-ray revealed massive bilateral
      pleural effusion. He had no sign of myopathy at this point. Pleural fluid was
      proved to be exudative and contained extremely high levels of hyaluronic acid. He
      was also complicated with interstitial pneumonitis and was given a pulse therapy
      with methyl prednisolone followed by daily administration of 55 mg prednisolone
      (PSL). Twenty days after the commencement of the therapy, pleural effusion
      decreased but muscle weakness gradually appeared, accompanied by elevation of
      myogenic enzymes. Myogenic changes on electromyogram, and irregularity of the
      muscle fibers with slight inflammatory cell infiltrates in a biopsy specimen were
      demonstrated. He was transferred to our hospital, and a diagnosis of
      dermatomyositis was made. Later, pleural effusion waxed and waned depending on
      the dosage of PSL, but no other causative disorder was demonstrated by extensive
      examinations. This case indicates that the pleuritis could be one of the
      vasculitic manifestations of dermatomyositis.

PMID- 16578973
TI  - [Patient with intravascular lymphomatosis: Changes with time in concentrations of
      serum cytokines].
AB  - Serum cytokines were evaluated in a patient with intravascular lymphomatosis
      (IVL). A 62-year-old man was admitted to our hospital for his general malaise,
      arthralgia, and high-grade fever. He was diagnosed as dermatomyositis, initially.
      His symptoms were improved by high dose of corticosteroid and immunosuppressive
      therapy. However his condition deteriorated gradually, and died ten months after
      the onset of symptoms. Postmortem examination revealed IVL (B cell type). The
      serum concentrations of inflammatory cytokines, IL-6 and TNF-alpha, were
      elevated. Level of serum IFN-y was high only at the end of his illness. Serum IL
      2 was not detected during the course. Serum IL-4 was slightly elevated. Elevated
      CRP and hypoalbuminemia might be related to the elevation of these inflammatory
      cytokines. The clinical diagnosis of IVL is usually difficult because of the
      absence of specific clinical manifestations and laboratory findings. The time
      course and/or concentrations of serum cytokines could be a key to make an early
      diagnosis.

PMID- 16578974
TI  - Military hardiness as a buffer of psychological health on return from deployment.
AB  - Military hardiness, the context-specific adaptation of psychological hardiness,
      is explored as it relates to military occupational stressors. It was hypothesized
      that military hardiness would moderate the effects of deployment stressors on
      soldier health. In a survey study of 629 U.S. soldiers, deployment stressors,
      military hardiness, and psychological and physical health were assessed during a
      peacekeeping deployment. Health was measured again after deployment. Results of
      moderated regression analyses partially supported the hypotheses; military
      hardiness moderated the impact of deployment stressors on depression after
      deployment, after controlling for depression during deployment. Implications for
      training military hardiness and applications to other occupational settings are
      discussed.

PMID- 16578975
TI  - Accession standards for attention-deficit/hyperactivity disorder: a survival
      analysis of military recruits, 1995-2000.
AB  - A retrospective cohort study was conducted to evaluate the Department of Defense
      practice of allowing some individuals with a history of attention
      deficit/hyperactivity disorder (ADHD) to enter military service (waiving for
      ADHD). Enlisted recruits who entered active duty with a waiver for academic
      problems related to ADHD were compared with control subjects who did not reveal
      health problems before entry, in terms of retention, promotion, and mental health
      related outcomes. A total of 539 recruits with a history of ADHD were retained at
      the same rate as 1,617 control subjects, with no differences in promotion rates,
      comorbid diagnoses, or mental health-related discharges. On the basis of these
      findings, the Department of Defense medical accession standards have been changed
      to allow applicants who reveal a history of ADHD but did not require medication
      to finish high school or to hold a job for at least 1 year the opportunity to
      enter active duty without going through the current waiver process.

PMID- 16578976
TI  - Distal-end aneurysm of the frontopolar artery with an atypical postoperative
      complication: case report.
AB  - OBJECTIVE: We present a unique case of a saccular aneurysm originating from the
      distal end of the right frontopolar artery (FPA). METHODS: This previously
      healthy, 54-year-old man had sustained a mild head trauma. On admission, he was
      lethargic, but his neurological examination results were otherwise normal.
      Neuroradiological studies (including brain computed tomography, magnetic
      resonance imaging, and cerebral angiography) demonstrated a distal-end aneurysm
      of the right FPA. The aneurysm was clipped and resected via a right frontal
      craniotomy. RESULTS: The postoperative course was uneventful. Pathological
      examination of the resected specimen confirmed rupture of the wall of a true
      aneurysm. The patient's medical history was also negative for trauma in the past,
      previous neurological disease, and vascular collagen disorders. Routine
      angiography performed 30 days postoperatively demonstrated complete occlusion of
      the right FPA. The patient was free of focal neurological deficits. CONCLUSION:
      This case demonstrates that not all distally located aneurysms are necessarily
      mycotic or traumatic.

PMID- 16578977
TI  - Antidepressant usage in the Canadian Forces.
AB  - This study was performed to evaluate the use of antidepressant medications among
      Canadian Forces (CF) members. A retrospective chart review was undertaken at
      seven CF bases for members who received antidepressant medications during a 6
      month period. Data were collected on doses, duration, and types of antidepressant
      drugs, indications for therapy, and prescriber characteristics. Indications were
      classified as depression, anxiety disorders (including post-traumatic stress
      disorder [PTSD]), or nonpsychiatric conditions. A total of 1,024 charts were
      reviewed. Antidepressant usage rates were similar across sites for depression and
      anxiety but differed for PTSD. Rates of PTSD demonstrated more variability than
      did rates of depression or anxiety disorders among CF members. Antidepressant
      therapy is also frequently prescribed for nonpsychiatric disorders. Indications
      for the use of antidepressants thus varied among CF members at different bases.
      Better detection and treatment of depression may be required in this population.

PMID- 16578978
TI  - Estimated leisure-time noise exposure, hearing thresholds, and hearing symptoms
      of Finnish conscripts.
AB  - The aim of this study was to set up a statistical measure for determine the total
      cumulative noise exposure of Finnish conscripts (n = 1,054) as a result of
      leisure-time noise activities. All of the conscripts underwent hearing screening.
      The conscripts' time in noisy activities and their rating of the loudness and
      estimated noise levels of the activities were used as the predictors in the risk
      analysis. Self-reported hearing symptoms (i.e., tinnitus, pain in the ear) and
      hearing loss due to noise exposure were also inquired about. Twenty-seven percent
      of the conscripts had weekly noise exposure to > 85 dBA. Approximately 20% of the
      conscripts had >20 dB hearing loss in either ear in the frequency range of 0.5 to
      8 kHz. The incidence of hearing symptoms seemed to correlate with an increased
      noise dose.

PMID- 16578979
TI  - A comparison of the military entrance processing station screening audiogram with
      the Defense Occupational and Environmental Health Readiness System reference
      audiogram at Fort Sill, Oklahoma, in 2000.
AB  - BACKGROUND: The Department of Defense Hearing Conservation Program requires that
      a reference audiogram be performed at initial entry training (IET), before noise
      exposure. In the Army, only Fort Sill, home of the field artillery, and Fort
      Benning, home of the infantry, are in compliance. All military applicants receive
      a screening audiogram at a military entrance processing station (MEPS) to qualify
      for service. This audiogram does not meet the Defense Occupational and
      Environmental Health Readiness System-Hearing Conservation (DOEHRS-HC) standard.
      Nevertheless, it has been proposed that the MEPS screen be used as the reference
      because of limited resources and time during IET medical in-processing. METHODS:
      A total of 11,816 individual reference audiograms performed at Fort Sill 95th
      Adjutant General Recruit Reception Center in 2000 were identified in the DOEHRS
      HC database. Results of the MEPS screening audiograms were found for 11,311 (96%)
      of these individuals. The two audiograms were compared by frequency and ear and
      by using the two Department of Defense criteria for threshold shift. RESULTS: A
      total of 14.49% (95% confidence interval, 14.48-14.50%) of audiograms using the
      three-frequency average difference and 23.19% (95% confidence interval, 23.18
      23.20%) using the four-frequency difference in either ear demonstrated a
      threshold shift. The mean difference in intensity between the two audiograms
      ranged from 5 to 12 dB and varied by frequency and ear, with the greatest
      differences being seen at 500 and 6,000 kHz and in the left ear, compared with
      the right ear. The mean threshold level was higher for each frequency in the
      DOEHRS-HC audiogram, compared with the MEPS audiogram. CONCLUSIONS: Approximately
      15% of soldiers at Fort Sill in 2000 showed a clinically significant threshold
      difference between their MEPS screening and the DOEHRS-HC baseline audiogram.
      Methodological variations in testing and interval noise-induced hearing loss
      could account for these differences. The results do not support the use of the
      MEPS screening audiogram as the reference audiogram. Compliance with the Hearing
      Conservation Program in the Army would require either improving MEPS testing to
      DOEHRS-HC standards or performing baseline audiograms at all five IET sites.

PMID- 16578981
TI  - Corrective otoplasty for symptomatic prominent ears in U.S. soldiers.
AB  - The purpose of this investigation was to evaluate U.S. Army soldiers who
      presented to the plastic surgery service with the inability to properly wear a
      government-issued Kevlar field helmet because of their prominent ear deformity.
      Between September 2000 and April 2002, four patients with prominent ears and
      helical rim skin abrasions with breakdown attributable to abutment from their
      helmets underwent open otoplasty with conchal bowl resection via a posterior
      approach. Symptomatic relief and cosmetic improvement were obtained, with no
      incidence of complications or recurrence during the follow-up period, which
      ranged from 9 to 22 months. All patients were able to wear their Army-issued
      Kevlar helmets without difficulty after surgery. Otoplasty is an effective,
      reliable procedure that has now been performed to alleviate symptoms in an
      otherwise asymptomatic patient population.

PMID- 16578980
TI  - Initial evaluation of N,N-diethyl-m-toluamide and permethrin absorption in human
      volunteers under stress conditions.
AB  - OBJECTIVES: This was a pilot study to determine (1) whether it is feasible to
      effectively blind human subjects to the presence of the insect repellents N,N
      diethyl-m-toluamide (DEET) and permethrin; (2) whether DEET affects the
      absorption of permethrin; and (3) whether combat videotape viewing and mental
      arithmetic are stressful. METHODS: Ten volunteers were exposed to DEET,
      permethrin, and stress (1-hour combat videotape plus mental arithmetic) in a
      double-blind, randomized, placebo-controlled trial. Outcome measurements included
      hemodynamics, plasma DEET and permethrin levels, and questionnaires to assess
      blinding. RESULTS: Highly sensitive serologic assays readily detected DEET but
      not permethrin. Staff members and subjects were effectively blinded to both. The
      videotape-math combination was stressful by both self-report and hemodynamic
      measures. CONCLUSIONS: It is possible to blind subjects with respect to DEET and
      permethrin. Permethrin on clothing does not enter the bloodstream at appreciable
      levels. Combat videotapes and mental arithmetic can be stressful.

PMID- 16578982
TI  - The war on severe acute respiratory syndrome: United States Forces Korea's
      campaign plan.
AB  - A mysterious new respiratory illness known as severe acute respiratory syndrome
      (SARS) has become the most perplexing infectious disease to emerge in the 21st
      century. From March to May 2003, it competed daily with the war in Iraq as the
      most sensational media event of the moment. U.S. personnel serving in the
      Republic of Korea represented the largest U.S. military population at risk for
      SARS. With tensions growing between Pyongyang and Washington, the United
      States/Republic of Korea alliance could not afford to be rendered combat
      ineffective by SARS. To remain mission ready, the U.S. Forces Korea (USFK)
      commander declared a "War on SARS" and directed his medical staff to develop a
      plan to prevent a SARS outbreak among USFK personnel. This article outlines the
      USFK campaign plan for the SARS epidemic and documents lessons learned for future
      outbreaks of highly infectious diseases.

PMID- 16578983
TI  - Avulsion of the extensor carpi radialis brevis insertion: a case report and
      review of the literature.
AB  - Injuries to the bases of the index finger and long finger metacarpals are unusual
      because of the stability of the carpometacarpal joints. Such stability is
      provided by the strong capsuloligamentous attachments and the unique bony
      architecture. Given the rare nature of these injuries, there is no consensus
      regarding the optimal management of avulsion fractures of the bases of the index
      finger and long finger metacarpals. Open reduction and internal fixation of the
      fracture, with anatomic repair of the extensor carpi radialis brevis or extensor
      carpi radialis longus, offers several advantages over closed treatment. A case
      report and a review of the literature are presented.

PMID- 16578985
TI  - U.S. Army Professional Filler System nursing personnel: do they possess
      competency needed for deployment?
AB  - The objective of this study was to identify the perceived readiness of U.S. Army
      Professional Filler System personnel in regard to nursing competency and
      readiness for deployment. A purposive sample of research participants (N = 131)
      from two military treatment facilities assigned to Great Plains Regional Medical
      Command responded to an electronic Readiness Estimate and Deployability Index
      (READI). The READI measures self-reported competencies in six dimensions of
      nursing readiness. Descriptive statistics and one-way analysis of variance were
      used to analyze the data. Although the research surveyed three levels of nursing
      skills (registered nurse, licensed practical nurse, and certified nursing
      assistant), the study results were noted to be quite parallel across the groups.
      Significant differences were noted throughout the six dimensions of the READI and
      between the two military treatment facilities in the dimensions of operational
      nursing competencies and personal and psychological readiness. Findings support
      the need for a structured core competency tool to provide succinct focused
      training to ensure deployment readiness.

PMID- 16578984
TI  - Management of phalangeal neck fractures in children.
AB  - Outcomes of phalangeal neck fractures among children are not uniformly good. Our
      purpose was to delineate factors that affect management and outcomes in the
      treatment of phalangeal neck fractures among children. The management and
      outcomes of phalangeal neck fractures among children over a consecutive 7-year
      period at the Denver Children's Hospital are reported. Fifteen children met the
      criteria for inclusion in the study. The average age was 6 years. Follow-up
      periods averaged 36 months. Distinct fracture patterns were classified according
      to the following system: type I, nondisplaced; type II, displaced. Displaced
      fractures were subdivided according to the fracture geometry, as follows: type
      IIa, transverse; type IIb, transverse with a proximally directed spike; type lIc,
      oblique. Fractures classified as type IIa were not reliably stable after closed
      reduction and immobilization. Delayed operative stabilization led to digital
      stiffness. The remaining fracture types were well managed with closed reduction,
      if necessary, and immobilization. Because of the unreliable stability of type IIa
      fractures, early operative stabilization is recommended.

PMID- 16578986
TI  - Endoscopic carpal tunnel release using the biportal technique.
AB  - The clinical study consisted of 27 patients and 30 hands that were operated on
      with the biportal endoscopic carpal tunnel release technique between 2000 and
      2002. The mean follow-up time was 28 months. The time to return to work or
      complete recovery was found to average 12 days. The rate of functional recovery
      was 93% (27 hands), and 90% of hands (26 hands) were free of symptoms at the time
      of publication. According to our study, we conclude that the biportal endoscopic
      technique is an effective method to attain patient comfort; it is a minimally
      invasive method with a low complication rate in experienced hands for surgical
      treatment of carpal tunnel syndrome. Military persons can return to work quickly,
      without deficits in hand skills, with the use of this technique.

PMID- 16578987
TI  - Dental caries risk assessment.
AB  - The United Kingdom Defence Dental Agency assesses United Kingdom servicemen as
      being at low, moderate, or high risk of developing morbidity during the next
      year, based on the examining dental officer's assessment of their dental status.
      The most frequent reason for assessing a patient as being at high risk of
      experiencing a dental emergency is the presence of extensive caries; however,
      dental officers' perceptions of which caries render a patient at high risk vary
      considerably. An investigation was carried out with records for Royal Air Force
      recruits who had been assessed as needing restorative work at their initial
      dental inspections but for whom this treatment had not been provided for > or = 1
      year. Intraoral radiographs taken at the initial dental inspection were examined,
      and the width of apparently sound dentine remaining between the edge of the
      carious lesion and the pulp was measured. The results indicate that, when there
      is > or = 2 mm of apparently sound dentine remaining, there is very little risk
      that the patient will experience symptoms during the next year. Personnel with a
      carious tooth with < 2 mm of sound dentine remaining should be classified as high
      risk.

PMID- 16578988
TI  - Psychological adjustment during Army basic training.
AB  - This study evaluated changes in depression, anxiety, and stress during Army basic
      training. During week 1 of training, 139 soldiers from two companies volunteered
      for participation. In week 8, 93 soldiers were available for retesting. Self
      reports of depressive symptoms and perceptions of stressfulness at both
      assessments fell within the normative range for nonclinical samples, whereas
      endorsement of anxiety symptoms remained slightly elevated, in the mild range.
      Women endorsed higher levels of anxiety (F = 8.87, p < 0.01) than did men. No
      gender or ethnicity differences were noted for changes in psychological distress
      over time. Regression analyses showed that subjects with the highest levels of
      initial distress on the anxiety, depression, and stress measures had the most
      change at the end of 8 weeks of training (r values between 0.61 and 0.39; all p <
      0.01). Results suggest that initial levels of psychological distress are slightly
      elevated for anxiety but most individuals adapt to the stress of basic training,
      with normal levels of distress by the last week.

PMID- 16578989
TI  - Phase I and pharmacokinetic study of once-daily dosing of intravenously
      administered busulfan in the setting of a reduced-intensity preparative regimen
      and allogeneic hematopoietic stem cell transplantation as immunotherapy for renal
      cell carcinoma.
AB  - We performed a Phase I and pharmacokinetic study of once-daily, intravenously
      administered busulfan in the setting of a reduced-intensity preparative regimen
      and matched sibling donor allogeneic stem cell transplantation for treatment of
      metastatic renal cell carcinoma. Seven male patients with metastatic renal cell
      carcinoma received intravenously administered busulfan at 3.2 mg/kg once daily on
      day -10 and day -9, fludarabine at 30 mg/m2 on day -7 through day -2, and equine
      antithymocyte globulin at 15 mg/kg per day on day -5 through day -2. The mean
      area under the plasma concentration-time curve (AUC) and the half-life of the
      first dose of intravenously administered busulfan were 6,253 microM x minute
      (range, 5,036-7,482 microM x minute) and 3.37 hours (range, 2.54-4.00 hours),
      respectively. The AUC was higher than predicted from extrapolation of AUC data
      for the same total dose of intravenously administered busulfan divided into four
      doses daily. Patients experienced greater than expected regimen-related toxicity
      for a reduced-intensity preparative regimen, and the study was stopped. In
      conclusion, this preparative regimen was associated with unacceptable regimen
      related toxicity among patients with metastatic renal cell carcinoma.

PMID- 16578990
TI  - The association between in-service sexual harassment and post-traumatic stress
      disorder among Department of Veterans Affairs disability applicants.
AB  - OBJECTIVE: The goal was to describe the association between post-traumatic stress
      disorder (PTSD) and in-service sexual harassment in a nationally representative
      sample of Department of Veterans Affairs PTSD disability applicants. METHOD: The
      study was a cross-sectional survey. RESULTS: Of 4,918 eligible veterans, 3,337
      (68%) returned surveys. Nonresponse bias appeared to be minimal. After adjustment
      for other reported traumas, women's reported in-service sexual harassment
      severity was significantly associated with PTSD symptom severity (p < 0.0001).
      The effect seen was about the same size as that seen for combat exposure among
      the men and for in-service sexual assault among the women. Men showed no
      association between in-service sexual harassment and PTSD (p = 0.33), although
      power was low for this test. CONCLUSION: Sexual harassment significantly
      contributed to female veterans' PTSD symptoms; its contribution to men's symptoms
      was unclear. We discuss mechanisms through which sexual harassment might affect
      PTSD symptom severity, including the possibility that sexual harassment sometimes
      meets the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
      definition of a criterion A stressor.

PMID- 16578991
TI  - Arnold-Chiari malformation type I in military conscripts: symptoms and effects on
      service fitness.
AB  - Arnold-Chiari I malformation (Chiari I) is a congenital disorder characterized by
      caudal herniation of cerebellar tonsils through the foramen magnum. The symptoms
      and signs include headaches precipitated by coughing or exertion, dizziness,
      visual or oculomotor symptoms, dysphagia, trunk or extremity dysesthesias,
      ataxia, and drop attacks indicating cerebellar or cervical cord lesion. The
      symptoms may be provoked by increased intracranial pressure. The mean age of
      onset of symptoms is 25 years; consequently, previously unidentified Chiari I
      malformations occur in military personnel. Chiari I is associated with deaths
      following minor trauma, with acute respiratory failure, and with transient
      quadriparesis occurring in contact sports. Furthermore, Chiari I symptoms may be
      aggravated by chiropractic manipulation. This report describes symptoms and signs
      of Chiari I in four military conscripts in the Finnish Defense Forces. It is
      important to detect Chiari I in military personnel to establish appropriate
      service fitness and safety for these patients.

PMID- 16578992
TI  - Binge drinking, drinking and driving, and riding with a driver who had been
      drinking heavily among Air National Guard and Air Force Reserve Personnel.
AB  - Heavy drinking is associated with significant health problems and increased risk
      for injury and death. Although several studies have investigated alcohol use
      among active duty and civilian populations, little is known about the alcohol use
      patterns of reserve personnel. This study examined the prevalence and correlates
      of binge drinking, driving after drinking, and riding in a vehicle with a driver
      who had consumed alcohol among 4,836 guardsmen and reservists who were taking
      part in basic military training (mean age = 21.3 years; 29.4% female). Forty-six
      percent reported one or more binge drinking episodes in the month before basic
      military training. Four percent drove after consuming five or more drinks, while
      8.9% rode as a passenger with a driver who had been drinking heavily. Several
      demographic, behavioral, and attitudinal correlates of risky drinking patterns
      were identified. Findings have potentially important implications for the health,
      safety, and military readiness of reserve personnel.

PMID- 16578993
TI  - Management of intractable angina pectoris with spinal cord stimulation.

PMID- 16578994
TI  - Inhalation injury after capsaicin exposure.
AB  - Pepper spray is defined as a non-lethal agent used in riot control and personal
      self-defense. Oleoresin capsicum (OC), derived from the fruit of plants in the
      Capsicum genus, commonly referred to as hot peppers or chilies, is the active
      agent used in many of these defense sprays. Although generally assumed to be safe
      and effective, the consequences of OC cannot be predicted with certainty.
      Nationwide there have been numerous reports of pepper spray-related injuries,
      including officers injured in pepper spray-related training exercises. This
      report details one officer's experience.

PMID- 16578995
TI  - Practicing medicine with respect.

PMID- 16578996
TI  - Mammographic changes related to different types of hormonal therapies.
AB  - OBJECTIVES: To determine the effects of different types of hormone therapies (HT)
      on mammographic breast density changes. MATERIAL AND METHOD: Between 1999 and
      2002, mammograms obtained before and 12-18 months after different types of HT in
      170 women were evaluated Estrogen alone (n = 66), or estrogen in cyclic (n = 59)
      or continuous (n = 45) combination with progesterone were used. The baseline
      mammographic density was classified according to the Breast Imaging Reporting and
      Data Systems (BI-RADS). The serial changes observed mammographically were
      categorized as follows; no change, minimal change (10-25% increased density),
      moderate change (26-50% increased density), and marked change (> 50% increased
      density). RESULTS: Twelve (7%) of the women developed an increase in parenchymal
      density after HT: Mammographic changes were minimal change in five (2.9%) of the
      women, moderate change in four (2.3%), and marked change in three (1.8%). No
      mammographic change was observed in women receiving cyclic estrogen-progesterone.
      A greater percentage of women who had undergone continuous estrogen-progesterone
      therapy (22.2%, 10 of 45) demonstrated more change than those who had estrogen
      alone (3%, 2 of 66). The difference was statistically significant (p < 0.01).
      CONCLUSION: Changes of increased density after HT was seen in only 7% of
      mammograms and depended on the selected hormone regimen.

PMID- 16578997
TI  - Placental weight and its ratio to birth weight in normal pregnancy at
      Songkhlanagarind Hospital.
AB  - OBJECTIVES: To quantify placental weight and its ratio to birth weight in normal
      pregnancy; and to determine whether abnormal placental weight and its ratio are
      associated with poor pregnancy outcomes. DESIGN: Prospective, cross-sectional
      study. MATERIAL AND METHOD: From January 1st, 2004, to December 31st, 2004,
      placentae were obtained from 238 normal pregnancies, between the 36th-40th
      gestational weeks. The trimmed and drained placenta was weighed and the mean
      placental weight at term was defined Distribution curves for placental weight and
      their ratios with gestational age were constructed. The outcomes for the
      intrapartum and perinatal periods were compared with normal placental weight, its
      ratio to the group above the 90th percentile and below the 10th percentile.
      Fisher's Exact Test was used to analyze the data. A p value < 0.05 was considered
      significant. RESULTS: The placental weight increased according to the birth
      weight (r = 0.450, p < 0.005). The mean placental weight at 36-40 gestational age
      was 519 g (SD = 89.01g). The mean placental weight to birth weight ratio was
      17.08%. This ratio decreased slightly with advancing gestational age. There was
      an association between placental weight below the 10th percentile and fetal
      distress (p = 0.003). Placental weight to birth weight ratio below the 10th
      percentile was also associated with fetal distress (p = 0.02). Placental weight
      above the 90th percentile was associated with newborns requiring neonatal
      intensive care admission (p = 0.016). CONCLUSION: The placental weight increased
      according to the birth weight. The placental weight to birth weight ratio
      decreased slightly with advancing gestational age. Abnormal placental weight and
      its ratio were significantly associated with some adverse pregnancy outcomes.

PMID- 16578998
TI  - Outcome of recurrent and persistent disease of malignant ovarian germ cell tumor:
      a retrospective analysis at King Chulalongkorn Memorial Hospital.
AB  - Malignant ovarian germ cell tumor has one of the most successful treatment
      outcomes in gynecological malignancy. More than 80% of the patients can be cured
      from this rare type of tumor However, patients with recurrent and persistent
      disease after primary treatment are still the problem of management. The present
      study has reviewed the treatment outcome of this cancer in King Chulalongkorn
      Memorial Hospital during the 12 years periodfrom 1993 to 2004. The overall cases
      of malignant ovarian germ cell tumor were 71 cases, 8 cases had recurrent disease
      after primary treatment and all cases received platinum-based chemotherapy for
      the salvage treatment. All patients in this group received long-term survival
      with median survival time of 87 months. In patients with persistent disease, 10
      cases that resisted to first line adjuvant chemotherapy. Cisplatin and Etoposide
      regimen was applied as second line treatment, but none of these patients received
      long term response. The survival outcomes in these 2 groups are significantly
      different. The overall survival from the treatment of malignant ovarian germ cell
      tumor in King Chulalongkorn Memorial Hospital was 85.1%. In conclusion, the
      outcome of treatment in patients with recurrent disease after non-platinum
      chemotherapy is excellent. Salvage therapy in this group should contain platinum
      based regimen. Patients whose disease persisted after platinum-containing regimen
      had a poor survival outcome.

PMID- 16578999
TI  - Differences in socio-economic status, service utilization, and pregnancy outcomes
      between teenage and adult mothers.
AB  - BACKGROUND: Teenage pregnancies put mothers at high-risks to many health-related
      complications and newborn infants to poor birth-outcomes. OBJECTIVE: The present
      study aimed to explore the relationship of socio-economic status, service
      utilization, and pregnancy outcomes between teenage and adult mothers. MATERIAL
      AND METHOD: The study design was a population-based prospective cohort study
      conducted in four districts located in different geographical areas of Thailand
      All pregnancies occurring within one year, in each of the selected districts as
      of October 2000, were identified and recruited as the study's cohorts. Data was
      collected by interviewing cohort-respondents and through reviewing medical
      records. RESULTS: The present study showed that teenage pregnancies accounted for
      13.3% of all pregnancies in the study area. Approximately two thirds of the
      teenage cohort (i.e. 68.8%) were 18-19 years of age, while the remaining cohort
      members were 14-17 years of age (i.e. 26.1% aged 16-17 years, and 5.1% aged 14-15
      years). The percentage of low-birth weights for teenage and adult mothers were
      15.1% and 8.8% respectively. A higher percentage of teenage mothers enrolled in
      or completed secondary or higher levels of education has had more abnormal
      deliveries in comparison with adult mothers. In comparison with the non-teenage
      mothers, a greater proportion of teenage mothers had insufficient income, did not
      own their homes/houses, were single parents, had fewer consultations with health
      personnel, did not plan their pregnancy, were pregnant for the first time, and
      delivered infants with low-birth weights. CONCLUSION: The prevalence of teenage
      pregnancies in Thailand remains high. Most teenage mothers and their newborn
      infants are vulnerable to a variety of potentially serious health problems, and
      accordingly need appropriate help and support.

PMID- 16579000
TI  - A phase II study of docetaxel and carboplatin in Thai patients with advanced non
      small-cell lung cancer.
AB  - OBJECTIVE: This phase II study aimed to assess the effectiveness of the docetaxel
      plus carboplatin combination in chemotherapy-naive Thai patients with advanced
      non-small-cell lung cancer (NSCLC). MATERIAL AND METHOD: Forty patients with
      Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, stage
      IIIB/IV NSCLC were enrolled in a phase H study between August 2001 and April
      2003. Docetaxel 75 mg/m2 and Carboplatin AUC = 6 were given every 3 weeks.
      Response to treatment and toxicity were graded using standard WHO criteria. The
      Thai Functional Living Index Cancer (T-FLIC) scale was used to assess the Quality
      of Life (QoL) of all treated patients. RESULTS: Forty patients (median age: 55
      years, range, 39-68 years; PS:0-1) were enrolled: one had stage IIIB disease with
      effusion, while thirty-nine had stage IV disease. Five patients were non
      evaluable due to death within the first cycle; two dying of febrile neutropenia
      and sepsis, two of pulmonary infection, and one of unknown etiology. Partial
      response (PR) was seen in 28.6% patients, stable disease (SD) in 25.7%, and
      progressive disease (PD) in 45.7%. The median survival time was 32 weeks and the
      1-year survival rate was 30.7%. Body mass index (BMI) was the only factor
      associated with survival time (univariate analysis: p = 0.006; multivariate
      analysis: p = 0.004). Other factors (gender, age, histology, ECOG PS, and
      glomerular filtration rate) were not predict for survival. The major treatment
      related toxicities were neutropenia (from 152 treatment cycles there were grade
      4: 19.7%; grade 3: 23.7%), febrile neutropenia (from 152 treatment cycles there
      was 3.95%), and diarrhea (grades 3/4: 0.66%). The QoL scores improved
      significantly throughout the treatment period. CONCLUSION: The regimen of
      docetaxel and carboplatin is active in advanced NSCLC and may be considered for
      first-line therapy.

PMID- 16579001
TI  - Prevalence of osteoporosis in Thai men.
AB  - BACKGROUND: Osteoporosis is a growing health problem not only in women but also
      in men. However, there is a scarcity of epidemiologic data to study osteoporosis
      in Thai men. OBJECTIVES: To examine the bone mineral density (BMD) and to
      determine the prevalence of osteoporosis in Thai men. MATERIAL AND METHOD: A
      total of 412 men (159 from Bangkok and 253 from Khon Kaen, respectively)
      averaging 51 +/- 16 years of age, were measured for BMD at the femoral neck and
      lumbar spine by dual energy X-ray absorptiometry (LUNAR Corporation, WI, USA).
      RESULTS: The peak BMD was observed in men 20-29 years of age at both the femoral
      neck (mean +/- SD, 1.10 +/- 0.15 g/cm2) and lumbar spine (mean +/- SD, 1.17 +/-
      0.13 g/cm2). The prevalence of osteoporosis in the entire group of subjects was
      12.6, 4.6 and 3.9 per cent at the femoral neck, lumbar spine and both sites,
      respectively. The prevalence of osteoporosis increased with advancing age and was
      significantly higher at the femoral neck in urban men than rural men (18.2 vs 9.2
      per cent, p < 0.05) but comparable at the lumbar spine (5.0 vs 4.3 per cent, p =
      0.81). The correlation between femoral neck and lumbar spine BMDs was 0.53 (p <
      0.001). In univariate analysis, increased age, lower weight and lesser height
      were each associated with lower femoral neck BMD, whereas only lower weight and
      lesser height were associated with lower lumbar spine BMD. However, when the
      three factors were entered simultaneously, only increased age and lower weight
      were significantly associated with lower femoral neck BMD and only lower weight
      had a significant association with lower lumbar spine BMD. CONCLUSION: The
      present study demonstrated descriptive BMD data, normal BMD reference values for
      diagnosis and reported the prevalence of osteoporosis in Thai men.

PMID- 16579003
TI  - Clinical manifestations of primary hyperthyroidism in the elderly patients at the
      out-patient clinic of Srinagarind Hospital.
AB  - The authors reviewed the outpatient charts diagnosed as hyperthyroidism at
      Srinagarind Hospital from June 1998-June 2004. The objective was to compare the
      clinical features of hyperthyroidism in patients older and younger than 60 years
      old. There were 922 cases enrolled, 84 cases (9.11%) were 60 years old and above.
      The female: male ratio was 3.4:1 and 4:1 and the mean ages were 64.2 +/- 3.7 and
      37.4 +/- 11.2 years old in the elder and younger group, respectively. The common
      presentations were dyspnea (94.1, 96.5%), weight loss (93.8, 87.9%) and
      palpitation (83.3, 93.1%) in the elder and younger, respectively. The more
      significant clinical presentations in the elder group were atrial fibrillation,
      weakness and anorexia whereas exophthalmos, goiter, heat intolerance and
      hyperhidrosis were not as frequent. Thus, the classic presentations often lacked
      in the elder group. Therefore, unexplained AF, weakness and anorexia should not
      exclude hyperthyroidism even with paucity of typical clinical features.

PMID- 16579002
TI  - Pioglitazone reduces urinary protein and urinary transforming growth factor-beta
      excretion in patients with type 2 diabetes and overt nephropathy.
AB  - OBJECTIVE: Increased urinary excretion of protein and transforming growth factor
      beta (TGF-beta) are associated with progression of diabetic nephropathy (DN).
      Thiazolidinediones (TZD) could reduce urinary protein excretion in patients with
      microalbuminuric DN. There is little data of patients with macroalbuminuric DN.
      Also, there are no available clinical data regarding the effect of TZD on TGF
      beta and type IV collagen in clinical DN. The present study was carried out to
      evaluate the effect of pioglitazone (PGZ), a member of TZD, on urinary protein,
      urinary TGF-beta, and urinary type IV collagen excretion in type 2 diabetic
      patients with macroalbuminuric DN. MATERIAL AND METHOD: Forty patients with type
      2 diabetes and overt nephropathy, proteinuria more than 500 mg/day, were randomly
      assigned to receive PGZ (30 mg/day, n = 24) or placebo (control group, n = 16),
      for 12 weeks. Blood pressure, plasma glucose, glycated hemoglobin, lipid profile,
      24-hour proteinuria, urinary TGF-beta and urinary type IV collagen were
      determined and compared. RESULTS: Glycemic control and blood pressure in both
      groups were not significant different. At baseline, the levels of proteinuria,
      urinary TGF-beta, and type IV collagen were not significant different between
      both groups. The geometric mean of urinary protein excretion in the PGZ group was
      progressively reduced from 1.64 to 0.98 gram/day (g/d), or 40.1% decrease which
      was significantly different (p < 0.05) from the 4.3% increase (from 1.72 to 1.80
      g/d) in the control group. Urinary TGF-beta excretion in the PGZ group was
      decreased by 47.8% which significantly differed from the 59.7% increase in the
      control group (p < 0.05). Urinary type IV collagen levels in the PGZ group were
      decreased by 35% which was slightly, but not significantly, different from the
      51.6% elevation in the control group (p = 0.06). CONCLUSION: Besides the
      effectiveness in blood sugar control, pioglitazone could salutarily reduce
      proteinuria and synthesis of TGF-beta as well as type IV collagen. These
      beneficial effects of pioglitazone on diabetic nephropathy are comparable to
      angiotensin converting enzyme inhibitors and angiotensin receptor blockers

PMID- 16579004
TI  - The limited protocol MRI in diagnosis of lumbar disc herniation.
AB  - OBJECTIVE: To assess agreement in detection of lumbar disc herniation (LDH)
      between limited and full protocol MRI. MATERIAL AND METHOD: 123 patients who
      requested lumbar MRI for diagnosis of disc herniation were assessed The full
      protocol MRI composed of sagittal T1-wi, sagittal T2-wi and axial T2-wi was
      performed on each patient. The sagittal T2-wi was selected as the limited
      protocol MRI. The limited and full protocols MRI of each patient were separately
      interpreted by three neuroradiologists to assess disc herniation and nerve root
      compression. The consensus results of limited and full protocol were compared.
      The diagnostic performance of each protocol was analyzed using surgery as the
      gold standard. RESULTS: There were 62 females and 61 males enrolled into the
      study between the age of 21-60 years old (means = 42.91 years). The duration of
      pain was 1-204 months (mean = 31.20 months). The degree of severity was mild in
      23.58%, moderate 45.52% and severe 30.89% of cases. Thirty-three cases were
      operated on. For detection of LDH, the limited protocol gave the same
      interpretation results as the full protocol (0 = 1.04, 95%CI = 0.94, 1.14 with
      accepted range of 0.95-1.05). In nerve root compression, the limited protocol was
      not accurate as the full protocol (0 = 0.75, 95%CI = 0.87, 0.63). The
      sensitivity, specificity, accuracy, PPV, NPV, and LR+ in the surgical group of
      limited protocol in diagnosis of LDH were 82.61%, 80%, 81.82%, 90.48%, 60.67%,
      4.13 and in nerve root compression were 54.84%, 100%, 57.58%, 100%, 12.5%
      respectively. The same statistics of full protocol MRI in diagnosis of LDH were
      82.61%, 70.80%, 78.79%, 86.36%, 63.64%, 2.75 and of nerve root compression were
      80.65%, 100%, 81.82%, 100%, 25% respectively. The sensitivity and specificity in
      diagnosis of LDH were not different in both protocols but the sensitivity of
      nerve root compression was statistically significant different (p < 0.013, 95%CI
      = -0.33, -0.25). CONCLUSION: The authors concluded that limited protocol MRI may
      replace full protocol MRI in diagnosis of LDH but not in nerve root compression.

PMID- 16579005
TI  - HRCT of pulmonary tuberculosis mimics malignancy: a preliminary report.
AB  - OBJECTIVE: To evaluate potential predictors of high resolution CT (HRCT) findings
      of pulmonary mass caused by tuberculosis (Tbc). MATERIAL AND METHOD: A
      retrospective study of chest HRCT was performed in 10 patients diagnosed as
      pulmonary Tbc. The size, characteristics of lesions, enhancement and mediastinal
      lymphadenopathy were interpreted. The final diagnosis was reached by laboratory
      and pathological specimens or clinical improvement from treatment of the Tbc.
      RESULTS: Of 10 patients, 6 were males and 4 were females. The mean age was 53.5
      years old. There were 13 masses analyzed. The mean size of the lesions was 2.3 cm
      and 53.8% had diameters more than 2 cm. The locations of lesions were right upper
      lobe (30.8%), right middle lobe (7.7%), right lower lobe (38.5%) and left upper
      lobe (23.1%). Calcification was found in two lesions. The HRCT findings were
      spiculated margin (76.9%), lobulated margin (23.1%), smooth margin (7.7%), ground
      glass opacity (23.1%), concave border (61.5%), polygonal shape (53.8%), air
      bronchogram (38.5%), pseudocavity (15.4%), pleural tag (30.8%), distortion of
      vessels (23.1%), satellite lesions (38.5%), and peripheral subpleural lesion
      (46.2%). Only 7 cases of enhanced study were available and two cases showed
      enhancement. Of the 10 cases, mediastinal lymphadenopathy was found in 8(80%)
      cases. The size of the lymph nodes was less than 2 cm in 6 cases and larger than
      2 cm in 2 cases. Other associated findings were pleural thickening or effusion
      (60%), evidence of volume loss (20%), emphysema (40%), and infiltrations (50%).
      CONCLUSION: Many characteristics of Tbc lesion on HRCT mimic reported malignant
      lesions. Re-evaluation of value of HRCT for controversial lesions is needed

PMID- 16579006
TI  - ADC measurements in various patterns of multiple sclerosis lesions.
AB  - OBJECTIVE: To determine the difference of mean apparent diffusion coefficients
      (ADC) among different patterns of focal multiple sclerosis (MS) lesions, to
      compare mean lesion ADC between 2 clinical subgroups and to correlate mean lesion
      ADC with disability. MATERIAL AND METHOD: Thirty seven patients (26 with
      relapsing-remitting multiple sclerosis (MS) and 11 with secondary-progressive MS)
      underwent both conventional and diffusion-weighted MR imaging of the brain. After
      creating ADC maps, region identification was done by using b = 0 images and T2
      weighted images. ADC values were measured for MS lesions and (NAWM). RESULTS: A
      total of 288 lesions were identified on the images. The mean ADC for the lesions
      was significantly higher than that of NAWM Hypointense T1 lesions (n = 221) had a
      significantly higher mean ADC than isointense T1 lesions (n = 67) in both
      nonenhancing lesions (n = 250) and enhancing lesions (n = 38). The enhanced rim
      of ring-enhancing lesions (n = 18) had lower ADC than the central nonenhanced
      portions. Confluent lesions (n = 62) had a substantially higher mean ADC than
      discrete lesion (n = 226). Mean lesion ADC of secondary progressive MS was
      significantly higher than relapsing remitting MS. No correlation between mean
      lesion ADC and (EDSS) score was found CONCLUSION: Quantitative diffusion-weighted
      imaging is useful to elucidate the heterogeneous pathological substrate of MS in
      different patterns of MS lesions, to differentiate 2 major clinical subgroups.

PMID- 16579007
TI  - The validity and reliability of the WHO Schedules for Clinical Assessment in
      Neuropsychiatry (SCAN Thai Version): Mood Disorders Section.
AB  - BACKGROUND: Mood disorders are one of the most prevalent psychiatric disorders
      that have early onset, are chronic and can cause functional impairment. It is
      therefore crucial to establish an accurate diagnosis for treatment and research
      purposes. OBJECTIVES: The authors aimed to test the validity and reliability of
      the WHO Schedules for Clinical Assessment in Neuropsychiatry (SCAN Thai Version):
      Mood Disorders Section. MATERIAL AND METHOD: First, psychiatrists competent in
      the use of the schedules and their underlying objectives tests the linguistic
      clarity of the Thai psychiatric schedules in four regions of the country. Then
      between October 2003 and August 2004, Reliability of SCAN: mood disorder section
      was tested among 30 participants, including mood disordered patients and normal
      volunteers. RESULTS: Based on reactions from Thais and consultations from
      competent psychiatrists, content validity was established. The duration of
      interviews for the mood disorder sections averaged 63.6 min (SD = 17.1). The
      inter- and intra-rater reliability kappa were 0.80 (0.77-0.83) and 0.86 (0.84
      0.88), respectively. The reliability of the majority of items reached substantial
      to almost perfect agreement; however, 1 item (1%) had only slight agreement and
      15 items (12%) had moderate agreement, and needed clarification of the scoring
      method CONCLUSION: The Mood Disorders Sections of the WHO Neuropsychiatry
      Schedules for Clinical Assessment (SCAN Thai Version) were effective tools for
      diagnosing mood disorders among Thais.

PMID- 16579008
TI  - Runaway youths and correlating factors, study in Thailand.
AB  - OBJECTIVE: To study differences between runaways and non-runaways in a mental
      health clinic and to study differences between runaways in a mental health clinic
      and legal / shelter system. MATERIAL AND METHOD: Psychiatric records of runaways
      and non-runaways from Vajira Hospital were collected from June 1994 to October
      2003. 21 cases in each group were studied in various factors. 21 runaway cases
      who were in child and adolescent shelters were interviewed by the researchers.
      RESULTS: Neglect, sexual abuse, rejection, poverty and truancy were more common
      in the runaway group. The runaway group had more conduct disorder and substance
      abuse. Physical abuse, authoritarian and being in custody were more common in
      runaways in shelters. CONCLUSION: Various factors correlate with running away.
      These factors lie beneath long before runaway has taken place and understanding
      and managing them help in preventing and prompt treatment.

PMID- 16579009
TI  - Three-dimensional frameless stereotactic-guided pedicle screw fixation of the
      spine: early experiences in King Chulalongkorn Memorial Hospital.
AB  - OBJECTIVES: To study the accuracy and safety of pedicle screw insertion by three
      dimensional frameless stereo-tactic-guided technique. MATERIAL AND METHOD: Twelve
      patients underwent spinal surgery using three- dimensional frameless stereo
      tactic-guided technique at King Chulalongkorn Memorial Hospital (KCMH) during
      June - December 2004. In all patients, post-operative CT scan of the operated
      spinal segments were obtained and evaluated for the position of each screw
      placed. Medical records were reviewed and all patients were interviewed by
      telephone to assess clinical outcomes and complications RESULTS: 5I pedicle
      screws were inserted in 12 patients. Postoperative CT scan of the instrumented
      spine revealed that 50 screws were considered grade I screw while one screw was
      considered grade II. No patient suffered direct vascular or neurological injury.
      CONCLUSION: Three-dimensional frameless stereotactic-guided technique provides
      additional safety to spinal instrumentation

PMID- 16579010
TI  - Unplanned intubation during anesthesia: review of 31 cases from the Thai
      Anesthesia Incidents Study (THAI study).
AB  - OBJECTIVES: To examine the causes, outcomes, and contributing factors associated
      with patients requiring unplanned emergency intubation for adverse respiratory
      events. METERIAL AND METHOD: Appropriate unplanned intubation incidents were
      extracted from the Thai Anesthesia Incidents Study (THAI Study) database
      conducted between February 1, 2003, and January 31, 2004, and analyzed using
      descriptive statistics. RESULTS: Thirty-one incidents of unplanned intubation
      were recorded, 21 of which were due to respiratory problems particularly after
      bronchoscopy with and without surgery of the upper airway. Six of the 21 cases
      (28.6%) were children under 10 years of age who suffered from papilloma of the
      larynx. Sixteen cases of the 31 cases (52%) of the unplanned intubations were due
      to inadequate ventilation; 13 cases (41%) due to laryngeal edema; 11 cases (36%)
      due to sedative agents. The other events were the result of unstable
      hemodynamics, severe metabolic acidosis, muscle relaxants, and intrapulmonary
      lesions. Eighteen cases of unplanned intubations (18/31) (58%) occurred in the
      Post-Anesthesia Care Unit, 5 cases (16%) in a ward, and 4 (13%) in the operating
      room. The reported contributing factors included inadequate experience, lack of
      supervision and the patient's condition. CONCLUSION: Major incidents of unplanned
      intubation occurred after bronchoscopy. Common contributing factors related to
      inadequate ventilation, airway obstruction, sedative agents and unstable
      hemodynamics. Quality assurance, additional training, and improved supervision
      tended to minimize the incidents.

PMID- 16579011
TI  - Effect of systematic psychological preparation using visual illustration prior to
      gastrointestinal endoscopy on the anxiety of both pediatric patients and parents.
AB  - BACKGROUND: Anxiety, a psychological response to stress, can affect a child
      undergoing medical procedures, and their family members. The purpose of the
      present study was to evaluate the benefit of detailed systematic information
      using a set of real photograph-based technical illustrations provided to both
      parents and patients before performing endoscopy on the level of anxiety.
      MATERIAL AND METHOD: All children eligible for gastrointestinal endoscopy were
      consecutively enrolled from December 2003 to May 2004. Before and after providing
      systematic psychological preparation, the parents and patients older than five
      years of age were asked to score their anxiety on the procedures using visual
      analogue scale (VAS). RESULTS: There were fifty-four patients enrolled during the
      study period Of these, twenty-five children were older than five years of age.
      The most common indication of gastrointestinal endoscopy was lower
      gastrointestinal bleeding. The esophagogastroduodenoscopy, colonoscopy, and both
      upper and lower endoscopies were performed in 50%, 37%, and 13% of the cases,
      respectively. The mean and standard deviation of VAS on anxiety of the parents (n
      = 54) before and after providing systematic information were 3.89 +/- 3.45 and
      1.90 +/- 2.46, respectively (p < 0.001). These values on anxiety of the children
      older than 5 years of age before and after providing systematic information were
      4.38 +/- 3.72 and 3.36 +/- 3.69, respectively (p = 0.143). There was no
      statistically significant impact of types ofp rocedure, level of education,
      family s income, age of children, and birth order on the level of anxiety.
      CONCLUSION: The preparatory intervention using systematic visual illustration of
      the technical procedures in children undergoing gastrointestinal endoscopy could
      significantly reduce the parents' anxiety.

PMID- 16579012
TI  - Integrated criteria of fine-needle aspiration cytology and radiological imaging
      for verification of breast cancer in nonpalpable lesions.
AB  - OBJECTIVES: To evaluate the accuracy of using radiologic, cytologic and
      integrated radiologic and cytologic criteria in diagnosis of nonpalpable breast
      lesions. MATERIAL AND METHOD: From January 2003 to May 2004, a prospective study
      of performing fine-needle aspiration biopsy (FNAB) was carried out at King
      Chulalongkorn Memorial Hospital on female patients with nonpalpable or vaguely
      palpable lumps that needed ultrasound localization for the direction and depth.
      RESULTS: There were 162 lesions from 150 patients, consisting of 29 malignant
      neoplasms (17.9%) and 133 benign lesions (82.1%). Of the 107 classified as
      subcentimeter focal lesions (< 1 x 1 cm2 in size), two of radiological malignancy
      were false and two others were falsely negative by cytology. While the 23
      large/ill-defined lesions (> 1.5 x 1.5 cm2 in size), one hiding malignant lesion
      adjacent to a prominent intraduct papilloma was missed. Two others had falsely
      negative cytologic diagnosis. The integrated criteria achieved accuracy and
      sensitivity of 97.5% and 93% compared with the cytology, 96.3% and 82.8% and the
      better scenario of radiology, 95.7% and 82.8% respectively. CONCLUSION: The
      integrated criteria provide the most accuracy rate and sensitivity rate for
      detection of malignancy in nonpalpable breast lesions.

PMID- 16579013
TI  - Dural sinus thrombosis in melioidosis: the first case report.
AB  - Melioidosis which is infection with Burkholderia pseudomallei, is an important
      cause of sepsis in India, southeast Asia and northern Australia. Mortality is
      high and treatment is problematic. Neurological melioidosis is unusual but
      meningoencephalitis, encephalomyelitis and brain microabscess can occur Dural
      sinus thrombosis is not an uncommon cerebrovascular disorder with various
      etiologies. Hypercoagulable state, pregnancy, dehydration, certain blood
      dyscrasia and contraceptive pills are common causes however meningitis and local
      head & neck infections may lead to this condition. Dural sinus thrombosis
      complicating septicemic melioidosis has never been reported. The authors report a
      42-year-old Thai man suffering from septicemic melioidosis with dural sinus
      thrombosis. He had high fever, headache, left hemiparesis, focal seizure and
      increased intracranial pressure. Diabetes and mild alcoholic cirrhosis were
      diagnosed in this admission. CT scan, MRI brain and MRV revealed superior
      saggital sinus thrombosis with complicating venous infarction over right
      posterior parietal lobe. Hemoculture demonstrated Burkholderia pseudomallei and
      CSF was acellular Investigations for causes of dural sinus thrombosis were all
      negative. This patient gradually improved after treatment with ceftazidime,
      antiepileptic drug and heparin without clinical recurrence. Neuromelioidosis is a
      rare syndrome that may present as brain abscess, encephalitis or
      meningoencephalitis. The authors report dural sinus thrombosis associated with
      septicemic melioidosis. The authors' hypothesis of venous thrombosis in the
      presented case is sepsis induced hypercoagulable state. Physicians should be
      aware of cerebral venous thrombosis in case of suspicious melioidosis with
      neurological involvement. Prompt treatment with intravenous heparin and
      antibiotic is potentially effective.

PMID- 16579014
TI  - Selective transcatheter embolization for treatment of post-traumatic hepatic
      artery and portal vein pseudoaneurysms.
AB  - The authors report a case of post-traumatic hepatic artery and portal vein
      pseudoaneurysms caused by blunt abdominal trauma, with multiple organ injuries
      including liver laceration. Abdominal spiral CT, CDS and DSA were performed to
      confirm the diagnosis. Both pseudoaneurysms were treated successfully with
      selective transcatheter embolization.

PMID- 16579015
TI  - Incontinentia pigmenti achromians of Ito: an ultrastructural study.
AB  - A clinico-pathological and EM study of a Thai boy with hypomelanosis of Ito, one
      of the neurocutaneous syndromes, is reported. At birth, typical skin
      hypopigmentation on the trunk and a hypopigmented streak on the left lower
      extremity were noted Associated cutaneous pathology shows a decrease of melanin
      granules within basal and malpighian keratinocytes. Ultrastructural studies
      highlight a normal appearance for basal and malpighian keratinocytes, but a lack
      of melanosomes in the malpighian cells. Melanosomes are also dramatically reduced
      in the basal keratinocytes, which appear small, single or clustered and
      surrounded by a membrane. Melanocytic degeneration has been observed and
      dendritic melanocytes contained various stages of nonmelanised (stage II),
      partially melanised premelanosome (stage III) and rarely stage 4 melanosomes. The
      authors observed an increase in the number of Langerhans cell which have not
      previously been described. There were unmyelinated axon of nerve containing
      melanosomes at the dermoepidermal junction. The significance of these findings
      will be worthwhile to note that abnormal nerve termination in close relationship
      with basal keratinocyte, degenerated melanocyte, premelanosomes and langerhans
      cell are important in explaining the pathogenesis of Hypomelanosis of Ito.

PMID- 16579016
TI  - International stem cell research; networking and collaboration.
AB  - Stem cell research has obtained more attention during the last decade because of
      its strong potential as a new tool to cure many chronic diseases. In addition,
      stem cell knowledge is an important basis for understanding pathophysiology at
      the cellular level and developing disease models for experimental research. There
      are different limitations on resources, budget, policy and regulation among
      countries. As a result, each country has particular advantages and disadvantages
      in stem cell research. This result in the establishment of international networks
      and collaborations to coordinate and promote stem cell research aimed at medical
      applications.

PMID- 16579017
TI  - Morality and rural knowledge to globalization.

PMID- 16579018
TI  - Imagerie du sein.

PMID- 16579019
TI  - Breast imaging: raising the bar.

PMID- 16579020
TI  - Breast cancer screening in Canada: a review.
AB  - Organized screening for breast cancer in Canada began in 1988 and has been
      implemented in all provinces and 2 of the 3 territories. Quality initiatives are
      promoted through national guidelines which detail best practices in various
      areas, including achieving quality through a client-service approach, recruitment
      and capacity, retention, quality of mammography, reporting, communication of
      results, follow-up and diagnostic workup, and program evaluation; it also offers
      detailed guidelines for the pathological examination and reporting of breast
      specimens. The Canadian Breast Cancer Data Base is a national breast cancer
      screening surveillance system whose objective is to collect information from
      provincial-screening programs. These data are used to monitor and evaluate the
      performance of programs and allow comparison with national and international
      results. A series of standardized performance indicators and targets for the
      evaluation of performance and quality of organized breast cancer screening
      programs have been developed from the data base. Although health care is a
      provincial responsibility in Canada, the collective reporting and comparison of
      results both nationally and internationally is beneficial in evaluating and
      refining both screening programs and individual radiologist performance. The
      results of Canadian performance indicators compare favourably with those of other
      well-established international screening programs. There are variations in
      performance indicators across the provinces and territories, but these
      differences are not extreme.

PMID- 16579021
TI  - Sonography of the breast: to core or not to core?

PMID- 16579022
TI  - Redefining ultrasound appearance criteria of positive axillary lymph nodes.
AB  - OBJECTIVE: To determine objective criteria for ultrasonography (US) appearance in
      the diagnosis of abnormal axillary lymph nodes (ALNs) and to assess
      retrospectively their accuracy in preoperative staging of patients with Breast
      Imaging Reporting and Data System (BI-RADS) Category 5 breast lesion. METHODS: US
      guided axillary fine-needle aspiration biopsy (FNAB) was performed for
      preoperative staging of BI-RADS Category 5 lesions in breast cancer patients seen
      at the Ottawa Regional Women's Breast Health Centre. Retrospectively, ALN
      morphology was classified into 3 categories based on US appearance: mass-like
      appearance, focal nodular cortical thickening (FNCT), and diffuse cortical
      thickening (DCT), the latter 2 with fatty hilum preservation and cortical
      thickening greater than 2 mm. Cytologic results from the FNAB were compared with
      axillary lymph node dissection (ALND) or sentinel lymph node procedure (SLNP),
      when available. Retrospective image-based classification was performed blind to
      pathology results and analyzed with Pearson's correlation coefficient, receiver
      operating characteristic (ROC) curves, and chi-square and Hosmer-Lemeshow tests
      against the cytologic ground truth. RESULTS: Eighty-six ALNs in 84 patients were
      sampled with an 18-gauge needle under US guidance. The number of passes per
      sample was related to adequate sampling of positive ALNs having mass-like
      morphology but not DCT or FNCT (p < 0.001). The most frequent morphologic
      presentation of the 86 ALNs was mass-like appearance of lymph nodes (45%),
      followed by DCT (35%) and FNCT (20%). Metastatic involvement was found in 34
      (87%) of 39 ALNs that were mass-like, in 9 (53%) of 17 ALNs with FNCT, and in 9
      (30%) of 30 ALNs with DCT. The kappa agreement between FNAB and ALND or SLNP was
      0.64 for mass-like lymph nodes, 0.7 for lymph nodes with DCT, and 1.0 for FNCT.
      Overall sensitivity and specificity were 94% and 89%, respectively, with a
      positive predictive value of 97% and negative predictive value of 80%.
      CONCLUSIONS: Using a 2-mm threshold, FNCT and DCT warrant US-guided FNAB by an
      experienced radiologist as much as do mass-like lymph nodes. When biopsy is
      positive, axillary dissection can be performed and the sentinel node technique
      avoided.

PMID- 16579023
TI  - Ultrasound appearance of chronic mammary duct ectasia.

PMID- 16579024
TI  - Magnetic resonance imaging of the breast: current indications.
AB  - Breast magnetic resonance imaging (MRI) plays an increasing role in the
      management of selected breast cancer patients. MRI is recognized as the most
      sensitive modality for the detection of invasive breast cancer. Several valuable
      clinical applications of MRI have emerged for breast cancer detection and
      diagnosis from clinical investigations. Breast MRI is helpful for women diagnosed
      with breast cancer who contemplate breast conserving surgery; it provides
      valuable information on the extent of the disease. MRI can also help assess for
      residual invasive cancer in patients who have undergone lumpectomy with positive
      margins at pathology. It is very reliable in differentiating scar tissue from
      recurrence at the lumpectomy site. MRI is also reliable in finding a breast
      cancer in women with axillary nodal metastases and unknown primary tumour. MRI
      can help to monitor the response to chemotherapy. Breast MRI could be a better
      screening tool than mammography in women with very high risks of developing
      breast cancer, such as breast cancer gene carriers and patients treated with
      chest radiation. Other potential uses of MRI include evaluation of the integrity
      of silicone breast implants and evaluation of the parenchyma in women with
      silicone gel implants or free injection of silicone gel. However, like any other
      technique, breast MRI has some drawbacks, including low-to-moderate specificity,
      high costs, and variability in technique and interpretation. Radiologists must
      have a clear understanding of valid indications and selection criteria to use
      this technique appropriately.

PMID- 16579026
TI  - Digital mammography: 2005.

PMID- 16579025
TI  - Breast procedures guided by magnetic resonance imaging.

PMID- 16579027
TI  - Breast cancer staging: the role of the radiologist.
AB  - The role of the breast radiologist has evolved over the past years, with an
      increasing involvement in patient care. Improvements in diagnostic technology and
      surgical techniques allow for better preoperative staging and surgeries with
      decreased morbidity. This article reviews the elements of investigation that are
      important to the surgeon and oncologist in optimizing care for the newly
      diagnosed breast cancer patient, with the 6th edition of the TNM classification
      of the American Joint Committee on Cancer used as a reference.

PMID- 16579028
TI  - [Morphological inversions during the ontogenesis of the ixodid ticks (Acari:
      Ixodidae) from the viewpoint of the hypermorphosis conception and their
      significance for systematics].
AB  - Morphological inversions during the ontogenesis of the ixodid ticks consist in
      the deranges of species-specific tendencies in the development of some external
      structures by the female line. The inversions, which included a wide range of
      organs and their fine structures, have been described for the first time in 14
      species of 4 from 7 Palearctic ixodid genera. Emphasis is placed on the study of
      the structures, which serve as differential characters for closely related
      species. It is shown, that the using of the structures subjected to inversions is
      unavoidable in systematics because of the great similarity of closely related
      species, especially in immature stages. It is established by the data on the
      variability of all active stages in the species distribution ranges, that the
      degree of the inversions manifestation may somewhat fluctuate in different
      subspecies or geographic morphotypes of the same species, but the peculiarity of
      the inversions always remains a species-specific character. The cause of
      inversions origin is the evolution of the Ixodidae by the way of morpho
      ecological specialization, namely hypertrophic, giantism, the growth of teguments
      in the period of nutrition act by pasture ambushing, which led to the derange of
      the development coordination of the organs during ontogenesis. Biological
      implication of the inversions is a guarantee of the adaptive potential of species
      during the process of microevolution. Even though the inversions make
      identification of closely related species difficult, their substantial importance
      is that they form integral species-specific character for the whole active part
      of the species ontogenesis.

PMID- 16579029
TI  - [Geographical variation in the species Montivagum dihumerale and speciation in
      chigger mites (Acari: Trombiculidae)].
AB  - Intraspecific morphological variation of the chigger mite species Montivagum
      dihumerale (Traub et Nadchatram, 1967) is studied. Eco-geographic rules of the
      variation are revealed. General size of mites is found to be increased along with
      the rise of the high-mountain character of the landscape in the collection
      localities. The numbers of idiosomal setae are varied independently from the size
      parameters and geographically close populations are proved to be the most similar
      by these characters. At the same time, numbers of the setae of different types
      play the leading role in the discrimination of closely related Montivagum
      species, while the eco-geographical rules have not been found in this genus at
      the level of interspecific differences. As a result, the hypothesis is set up,
      that a significant degree of isolation of local populations separated from each
      other by high mountain ranges of the Central Asia is the main factor of
      speciation in the genus Montivagum. Regional character of this speciation mode is
      confirmed by the comparison with other chigger mites taxa.

PMID- 16579030
TI  - [Development of mother sporocysts of Echinostoma caproni (Trematoda:
      Echinostomatidae)].
AB  - New data on the migration and development of Echinostoma caproni mother
      sporocysts in two mollusk species of the genus Biomphalaria are obtained. It is
      confirmed, that the formation of primary and second generative cells takes place
      only as a result of undifferentiated cells' proliferation and following
      differentiation of some of them. These processes in miracidium, as well as in the
      parasitic stage of mother sporocyst, take place in a special organ, germinal
      mass, which occupies caudal position in both cases. The supposition of the role
      of germinal mass as the universal centre of multiplication and development of
      generative elements in all generations of Echinostoma caproni parthenites is
      confirmed. It is established, that mother sporocysts do not relize their
      reproductive potential completely, and the degree of its realization depends on
      the conditions arising in the host organism.

PMID- 16579031
TI  - [Description of a new cestode species Mircia shigini gen. et sp. n.
      (Cyclophyliidea: Schistotaeniidae)].
AB  - A new genus and species of cestodes from the great-crested grebe Podiceps
      cristatus collected in the Eastern Europe is described. The genus Mircia gen. n.
      in addition to the type species M. shigini gen. n. includes the following species
      formerly being included in the genus Joyeuxilepis Spassky, 1947: M. decacantha
      (Fuhrmann, 1913) comb. n., M. decacanthoides (Borgarenko et Gulyaev, 1991) comb.
      n., M. fimbriata (Borgarenko, Spasskaja et Spassky, 1972), comb. n., and M.
      uralensis (Gulyaev, 1989) comb. n. Brief revision of the genus Joyeuxilepis is
      provide.

PMID- 16579032
TI  - [Microsporidiosis of the dragonfly Aeshna viridis larvae (Odonata: Aeshnidae)
      caused by Systenostrema alba Larsson, 1988 (Microsporida: Thelohaniidae)].
AB  - A microsporidian species producing octospores in sporophorous vesicles is found
      in Aeshna viridis larvae from intermittent streams situated in the vicinity of
      Novosibirsk City. Size of the spores measured on fresh smears was 6.9 +/- 0.09
      microm x 4.1 +/- 0.08 microm (6.0-7.6 x 3.5-4.9). Each spore have single
      elongated nucleus and an anisofilar polar filament composed of 10-11 anterior and
      10-11 posterior coils. The infection was restricted to adipose tissue. According
      to spore morphology the Siberian isolate can be attributed to the species
      Systenostrema alba described from Aeshna grandis in Sweden (Larsson, 1988). This
      is the first description of Microsporidia infecting Odonata from Siberia.

PMID- 16579033
TI  - [An effect of the microsporidian Vairimorpha ephestiae (Microsporidia:
      Burenellidae) on activity and spectrum of nonspecific esterases in different
      tissues of the greater wax moth galleria mellonella (Lepidoptera: Pyralidae)
      larvae].
AB  - The effect of the microsporidian Vairimorpha ephestiae Matted (Microsporidia:
      Burenellidae) on nonspecific esterases was studied in hemolymph, fat body and
      midgut of the larvae of Galleria mellonella L. (Lepidoptera: Pyralidae). Esterase
      patterns were analyzed by the polyacrylamide gel electrophoresis, the total
      esterase activity was detected spectrophotometrically. The increase of total
      esterase activity was registered in hemolymph of inflected larvae. An
      overexpression of esterase isozyme in hemolymph was already detected at the 3rd
      day post infection. No changes in esterases pattern were observed in the fat
      body's homogenates of the G. mellonella larvae possessing the symptoms of
      microsporidiosis. The degradation of esterase isozymes and the decrease of total
      esterase activity in the pattern of the midgut homogenates of infected larvae
      were registered during parasite sporogony. The greatest esterase activity in
      hemolymph and midgut tissues was registered during vegetative reproduction of
      parasite, but the least level of esterase activity was observed during mass
      sporogony of microsporidia.

PMID- 16579034
TI  - [Solearhynchus rhytidotes nov. comb. (Palaeacanthocephala: Echinorhynchidae), a
      parasite of soles (Soleidae)].
AB  - On the base of literature and the original data in has been established that
      acanthocephalan species known as Acanthocephaloides kostylewi Meyer, 1933, and
      described from the Black Sea sole Solea lascaris nasuta (Pallas) is to be
      transferred to the genus Solearhynchus with new species name Solearhynchus
      rhytidotes nov. comb. (syn. Echinorhynchus rhytidotes Monticelli, 1905; E.
      aurantiacus Monticelli, 1887; E. corrugatus Monticelli, 1887; Acanthocephaloides
      kostylewi Meyer, 1933; A. rhytidotes (Monticelli, 1904) Belofastova et
      Korniychuc, 2000; Solearhynchus soleae (Porta, 1905) de Buron et Moillard, 1985).
      Detailed descriptions, measurements and original figures are given.

PMID- 16579035
TI  - [A new blackfly species Cnetha itelmenica sp. n. (Diptera: Simuliidae) from
      Kamchatka].
AB  - The description of a new species Cnetha itehnenica Chubareva et Yankovsky, sp. n.
      is given. Only 6 species of the genus Cnetha have the simple lobes of rectal
      organ (C. fontia, C. garniensis, C. gejgelensis, C. costata, C. subcostata and C.
      karzhantavica). These species distribute only in Southern Europe, Northern Africa
      and Transcaucasia, excluding C. subcostata distributed in NE China, Korea and
      Japan. C. itelmenica differs from C. fontia and C. garniensis in having a deep
      inlet of the head capsula, from C. costata, C. subco- stata and C. karzhantavica
      in the different number of hook rows in the posterior circlet (86-90 versus 96
      100 in C. gejgelensis and C. costata, 68 in C. karzhantavica). The new species
      differs from other Siberian and Far Eastern species of the genus (C. cornifera,
      C. paracornifera, C. patrushevae, C. pugetensis, C. shutovae) in having simple
      lobes of the rectal organ, from C. gejgelensis in having another pattern of setae
      arrangement on the submentum (by 1 line, versus 2 lines in C. gejgelensis), from
      C. shutovae, C. pugetensis and C. patrushevae in the different number of hook
      rows in the posterior circlet (86-90 versus 60-62 in C. shutovae and 62-66 in
      remains), and from C. pugetense and C. patrushevae in the number of primary fans
      (36-40 versus 41-52). C. itelmenica differs from C. vernum (as base standard), as
      well as from other studied species of the genus, in having a species-specific
      disk pattern, three wide homozygous inversions in IS, IL, IIIL, and a little
      homozygous inversion in IIS. It differs from C. fontia, C. garniensis, C. costata
      and C. zakhariensis in the absence of chromocenter and presence of additional
      heterochromatic B-chromosomes.

PMID- 16579036
TI  - The criminal code still unchanged as regards animal cruelty.

PMID- 16579037
TI  - An ethicist's commentary on the veterinarian's failure to prescribe as much as
      his or her colleagues.

PMID- 16579038
TI  - Clinical efficacy and safety of transdermal methimazole in the treatment of
      feline hyperthyroidism.
AB  - Thirteen cats, newly diagnosed with hyperthyroidism, were treated with a
      transdermal formulation of methimazole at a dose of 5 mg (0.1 mL) (concentration
      of 50 mg/mL) applied to the internal ear pinna every 12 h for 28 d. Baseline
      hematologic and biochemical values, along with serum thyroxine (T4) levels, were
      obtained on presentation (day 0). Cats were evaluated at 14 d (D14) and 28 d
      (D28) following transdermal therapy. At each visit, a physical examination, a
      complete blood cell count, a serum biochemical analysis, and a serum T4
      evaluation were performed. Ten cats completed the study. Clinical improvement, as
      well as a significant decrease in T4, was noted in all cats. Serum T4 measured at
      D14 and D28 were significantly lower at 27.44 nmol/L, s = 37.51 and 14.63 nmol/L,
      s = 10.65, respectively (P < 0.0001), as compared with values at D0 (97.31
      nmol/L, s = 37.55). Only 1 cat showed a cutaneous adverse reaction along with a
      marked thrombocytopenia. The results of this prospective clinical study suggest
      that transdermal methimazole is an effective and safe alternative to conventional
      oral formulations.

PMID- 16579039
TI  - Management factors affecting stereotypies and body condition score in nonracing
      horses in Prince Edward Island.
AB  - In North America, there are few representative data about the effects of
      management practices on equine welfare. In a randomized survey of 312 nonracing
      horses in Prince Edward Island (response rate 68.4%), owners completed a
      pretested questionnaire and a veterinarian examined each horse. Regression
      analyses identified factors affecting 2 welfare markers: body condition score
      (BCS) and stereotypic behavior. Horses' BCSs were high (mean 5.7, on a 9-point
      scale) and were associated with sex (males had lower BCSs than females; P <
      0.001) and examination date (P = 0.052). Prevalences of crib biting, wind
      sucking, and weaving were 3.8%, 3.8%, and 4.8%, respectively. Age (OR = 1.07, P =
      0.08) and hours worked weekly (OR = 1.12, P = 0.03) were risk factors for
      weaving. Straw bedding (OR = 0.3, P = 0.03), daily hours at pasture (OR = 0.94, P
      = 0.02), and horse type (drafts and miniatures had a lower risk than light
      horses; P = 0.12) reduced the risk of horses showing oral stereotypies. Some of
      these results contradict those of other studies perhaps because of populations
      concerned.

PMID- 16579040
TI  - Owner experiences and complications with home use of a replacement low profile
      gastrostomy device for long-term enteral feeding in dogs.
AB  - The purpose of this study was to evaluate complications and owner impressions of
      a low profile gastrostomy device (LPGD) for enteral feeding in dogs. Medical
      records of dogs that had placement of a percutaneous endoscopic gastrostomy tube
      followed by a LPGD between 1995 and 2003 were reviewed. Fifteen dogs had 29
      devices placed for a variety of disease states in which enteral nutritional
      support was indicated. The individual tubes were placed for a median duration of
      212 d. Most complications occurred more than 15 d after placement and were of no
      health risk to the animals. The most common reason for LPGD replacement was
      leakage through the 1-way antireflux valve. Fourteen of 15 owners that were
      contacted were supportive of the device. Based on its durability, ease of
      placement, minor complications, and positive owner impressions, we conclude that
      the LPGD is a valuable device for long-term enteral nutritional support of dogs.

PMID- 16579042
TI  - Bilateral 'gut-tie' in a recently castrated steer.
AB  - Small intestinal obstruction caused by 2 fibrous bands was found in a steer.
      Distended small intestine was palpable per rectum. Each band was located
      bilaterally between the caudal abdominal wall and the pelvic inlet. The
      compromised portion of intestine was considered nonviable and the animal was
      euthanized.

PMID- 16579041
TI  - Diagnosis of deafness in a horse by brainstem auditory evoked potential.
AB  - Deafness was confirmed in a blue-eyed, 3-year-old, overo paint horse by brainstem
      auditory evoked potential. Congenital inherited deafness associated with lack of
      facial pigmentation was suspected. Assessment of hearing should be considered,
      especially in paint horses, at the time of pre-purchase examination. Brainstem
      auditory evoked potential assessment is well tolerated and accurate.

PMID- 16579044
TI  - A prospective comparison of postoperative morbidity associated with the use of
      scalpel blades and lasers for onychectomy in cats.
AB  - This study compared patient discomfort for 10 d following feline onychectomies
      performed using a CO2 surgical laser versus a scalpel blade. Both techniques
      appeared to result in discomfort of a similar duration, although the laser caused
      significantly less lameness than blade excision during the first 7 d.

PMID- 16579043
TI  - Bilateral renal agenesis in an alpaca cria.
AB  - A 3-day-old male alpaca cria was presented for lack of vigor and failure to
      urinate since birth. Based on the history, laboratory data, ultrasonographs,
      surgical findings, and postmortem examination, the cria was diagnosed with
      bilateral renal agenesis and hypoplastic bladder, a congenital condition rarely
      seen in veterinary medicine.

PMID- 16579045
TI  - Ovarian remnant in a 2-year-old queen.
AB  - A 2-year-old domestic shorthair queen was presented for recurrent estrus
      behavior. Ovariohysterectomy had been performed 9 months earlier. An ovarian
      remnant was diagnosed, based on vaginal cytology and hormonal stimulation.
      Following exploratory laparotomy to remove the aberrant tissue, the animal
      recovered without further complications.

PMID- 16579046
TI  - Gender-specific animal references: anthropomorphic pandering or quality client
      communication?

PMID- 16579047
TI  - What's new in orthopedics--part II.

PMID- 16579048
TI  - Diagnostic dermatology.

PMID- 16579049
TI  - Veterinary diagnostic imaging. Ruptured lung lobe abscess secondary to a
      localized alveolar disease.

PMID- 16579050
TI  - [Lack of antidepresant-like activity of some ligands of polyamine binding sites
      of NMDA receptors in models of depression].
AB  - Arcain and a series of the partial modulators of polyamine binding sites of NMDA
      receptors (spermine- and adamantyl-containing polyamines IEM-1460, IEM-1490, IEM
      1592, IEM-1755) do not display (in contrast to melipramine and memantine)
      antidepressant-like action in the forced swimming test and reserpine-induced
      depression test in rats. Compounds IEM-1460, IEM-1490, IEM-1592 increase the
      total time of immobilization in the Porsolt test, probably, by facilitating the
      development of stress-induced depression. It is supposed that the prodepressant
      activity of these compounds is mediated by NMDA-receptors having NR1/NR2C and
      NR1/NR2D subunit composition.

PMID- 16579051
TI  - [Neurochemical features of the ventral pallidum in realization of the
      antiaversive effects of anxiolytics in different models of anxiety].
AB  - Preliminary intraperitoneal injections of some combinations of adreno- and
      dopaminomimetics, monoamines, and mediator amino acids (as well as of their
      agonists and antagonists) followed by microinjections of the same combinations
      into the ventral pallidum reveal differences in the functional significance of
      the neurochemical profile of this paleostriatum formation in realization of the
      anxiety states of different genesis, as manifested in the "illuminated site
      avoidance" and the "threatening situation" tests in rats. The pharmacological
      analysis based on the local injection of anxiosedative and anxioselective agents
      into the ventral paleostriatum showed that the antiaversive action of campirone
      is revealed under the conditions of dominating fear motivation, while that
      analogous action of chlordiazepoxide, phenibut and indoter is revealed under
      negative stressful zoosocial impacts and is realized by serotonin- and GABA-ergic
      (rather than by cathecholamine- and glutaminergic) aversive systems of the
      ventral pallidum.

PMID- 16579052
TI  - [Effect of 8-OH-DPAT on the depressive behavior and monoamine metabolism in the
      hippocampus of ovariectomized rats].
AB  - The influence of the chronic administration of the 5-HT1A receptor agonist 8-OH
      DPAT (0.05 mg/kg, s.c.) and the 5-HT1A receptor antagonist NAN-190 (0.1 mg/kg,
      i.p.) alone or in combination with 17beta-estradiol (0.5 microg per animal, i.m.)
      for 14 days on the depression behavior and the monoamine level in hippocampus has
      been studied in adult ovariectomized (OVX) female rats. The model of depression
      in rats was realized under the Porsolt test conditions. The levels of monoamine
      and its metabolites were determined using HPLC. It was established that the
      chronic administration of 8-OH-DPAT alone produces an antidepressant effect in
      OVX rats. The chronic administration of 8-OH-DPAT in combination with 17beta
      estradiol potentiated the antidepressant action of both preparations. The
      antidepressant effect of 8-OH-DPAT in OVX rats was correlated with the
      restoration of noradrenergic, serotoninergic, and dopaminergic neurotransmission
      in the hippocampus. The obtained data are indicative of a close interaction
      between the ovarian hormonal system and the cerebral serotoninergic system in the
      realization of depression mechanisms.

PMID- 16579053
TI  - [Effect of xymedone on high-voltage-activated Ca2+ currents in pyramidal neurons
      of the entorhinal cortex].
AB  - The effect of xymedon on Ca2+ currents in entorhinal cortex LIII pyramidal
      neurons was studied using brain slices from 10-17-day old rats, which were
      analyzed by means of the infrared video assisted whole cell patch clamp
      recording. The sample slices were superfused with artificial cerebrospinal fluid
      containing tetrodotoxin, 4-aminopyridine, and tetraethylammonium for the blocking
      of Na+ and K+ channels, respectively. Xymedone was added to artificial
      cerebrospinal fluid and to all extracellular solutions. The slices were exposed
      to different concentrations of xymedone for 3 hours followed by patch-clamp
      recordings. Control recordings were run with the vehicle. Xymedone in a
      concentration of 0.01 mM decreased the maximum voltage-dependent Ca2+ current
      amplitude by 39.8 %, while 1 mM of xymedone inhibited the Ca2+ currents almost
      completely. The obtained data showed for the first time that xymedone exhibits a
      calcium channel blocker activity in neurons. Possible neuroprotective mechanisms
      of xymedone are discussed.

PMID- 16579054
TI  - [Effect of melatonin on memory, individual time perception, and anxiety in young
      people of different chronotype groups].
AB  - Chronic administration of the pineal hormone melatonin in a low dose (0.75 mg)
      improved memory and optimized individual time perception in a group of young
      volunteers. These changes were pronounced even two weeks after termination of the
      drug administration. The expression of the melatonin effect was depended on the
      chronotype of humans tested.

PMID- 16579055
TI  - [Effect of the class III antiarrhythmic drug nibentan in vagotonic atrial
      fibrillation].
AB  - Nibentan, the class III antiarrhythmic drug, was experimentally investigated in
      anaesthetized dogs using the model of vagotonic atrial fibrillation. Under the
      conditions of vagus nerve stimulation, nibentan retained the ability to prolong
      the ventricular repolarization and increase the effective refractory periods and
      to maintain the frequency-independent action on the effective refractory periods
      of the atrium. At the same time, nibentan did not affect conduction via the His
      Purkinje system and prevented bradycardia induced by vagus stimulation. The drug
      was found to depress the conduction in atrium, this effect being retained on the
      background of vagus nerve stimulation. Nibentan has proved to be effective in
      preventing the vagotonic atrial fibrillation.

PMID- 16579056
TI  - [Effect of phenibut on the respiratory arrest caused by serotonin].
AB  - The role of the GABAergic system in mechanisms of the respiratory arrest caused
      by serotonin administration was studied in anaesthetized rats. Under normal
      conditions, the systemic administration of serotonin (20-60 mg/kg, i.v.) resulted
      in drastic changes of the respiratory pattern, whereby the initial phase of
      increased respiratory rate was followed by the respiratory arrest. The
      preliminary injection of phenibut (400 mg/kg, i.p.) abolished or sharply reduced
      the duration of the respiratory arrest phase induced by serotonin. Bilateral
      vagotomy following the phenibut injection potentiated the anti-apnoesic effect of
      phenibut, which was evidence of the additive action of vagotomy and phenibut
      administration. The mechanism of apnea caused by serotonin administration is
      suggested to include a central GABAergic element, which is activated by phenibut
      so as to counteract the respiratory arrest.

PMID- 16579057
TI  - [The role of lipid peroxidation and antioxidant defence system of the kidneys in
      the predisposition to gentamicin-induced nephrotoxicity in rabbits].
AB  - A correlation is established between individual features of the lipid
      peroxidation processes and the state of the system of antioxidant protection of
      the kidney in intact rabbits and their susceptibility to gentamicin
      nephrotoxicity. The level of gentamicin-induced damage of the kidney is more
      significant in rabbits with increased concentration of malonic dialdehyde in the
      kidney, which is generated by a NADPH-dependent enzyme system. A decreased level
      of reduced glutathione, as well as the enzymopathy with respect to superoxide
      dismutase and catalase are among the factors aggravating gentamicin-induced
      kidney lesion.

PMID- 16579058
TI  - [Effect of bemithyl on sexual behavior and spermatogenesis in rats].
AB  - Bemithyl produced different influence on the sexual behavior (pairing motivation)
      and spermatogenesis in rats, depending on the dose and duration of drug
      administration. A three-day administration of bemithyl (20 and 200 mg/kg, p.o.)
      stimulated the sexual activity and spermatogenesis in male rats irrespective of
      the drug dose. The chronic administration of bemithyl over a period of 60 days
      led to a decrease in the male sexual activity and spermatogenesis index. This
      behavior can be related to the drug influence on the hypothalamus/pituitary
      structures responsible for the male rat generative function.

PMID- 16579059
TI  - [Myelotoxity of the nuclear enzyme inhibitors irinotecan and etoposide].
AB  - Irinotecan (campto) and etoposide cause the loss cells due to apoptosis, the
      early development of hypoplasia in bone marrow and lymphoid organs, and
      pancytopenia in peripheral blood upon single intravenous injection in maximum
      tolerated doses to white outbred rats. Etoposide causes more severe apoptosis and
      myelotoxicity than irinotecan. The changes are reversible within one to three
      months. On longer terms (from three to six months) after irinotecan and etoposide
      injection, there were a moderate decrease in the red blood cells and hematocrit,
      an increase of the MCV and MCHC indices, and premature thymus involution.

PMID- 16579061
TI  - [Effect of immunomodulators on liver regeneration].
AB  - The directed influence of immunomodulators on various chains of the immune system
      makes possible the control over liver restoration processes, as demonstrated on
      the model of hepatic resection. It is established that macrophages together with
      T-lymphocytes play a very important role in the process of liver regeneration.

PMID- 16579060
TI  - [Antioxidative effects of isoflavon genisteine-8-C-glycoside in vitro and in
      vivo].
AB  - Bioflavonoids (polyhydroxyphenols) are ubiquitous components of plants, fruits
      and vegetables; these compounds are efficient scavengers of free oxygen radicals
      and peroxides. The aim of this study was to investigate the antioxidative effects
      of genistein-8-C-glycoside (G8CG) isolated from the flowers of Lipinus luteus L.
      G8CG dose-dependently inhibited membrane lipid peroxidation and prevented GSH
      oxidation in human red blood cells and rat liver homogenates under tert
      butylhydroperoxide-induced oxidative stress and single whole-body gamma
      irradiation (1 Gy) of rats.

PMID- 16579062
TI  - [Comutagen interaction of verapamil and ribavirin].
AB  - The chromosome aberration assay in the bone marrow cells of C57BL/6 mice was used
      to study the cytogenetic activity of ribavirin (10, 50, 100, 200, and 400 mg/kg,
      p.o.) alone and in combinations with verapamil (0.25, 2.5, 5, and 10 mg/kg,
      p.o.). It was established that ribavirin was cytogenetically active upon single
      administration in a dose of 200 and 400 mg/kg, and it was also active in a dose
      of 50 and 100 mg/kg when administered for 5 days in combination with verapamil in
      a dose of 5 or 10 mg/kg and 2.5, 5, or 10 mg/kg, respectively. These results
      indicate that verapamil and ribavirin exhibit comutagen action.

PMID- 16579063
TI  - [Effects of ionic and non-ionic roentgen-contrast media upon ex vivo hemostasis
      in rabbits].
AB  - The influence of ionic and non-ionic contrast media on the ex vivo hemostasis in
      rabbits was studied for ionic urografin (76 %), non-ionic ultravist-300, and non
      ionic omnipaque-300 intravenously injected in medium and high doses (1.5 ml/kg
      and 3.0 ml/kg, respectively). Ionic urografin (1.5 ml/kg) almost did not
      influence the level of hemostasis ex vivo. Non-ionic contrast media (ultravist
      and omnipaque) in the medium diagnostic dose (1.5 ml/kg) activated the
      hemostasis, the effect being much more pronounced in the case of omnipaque. Dose
      dependent action was observed for both ionic and non-ionic contrast media.

PMID- 16579064
TI  - [Evaluation of metabolic parameters in vitro as a model for testing the
      cytotoxicity of antiviral drugs].
AB  - A new test system based on in vitro assessment of the cellular viability and/or
      metabolism is proposed, which offers an informative approach to the screening of
      antiviral drugs. Cytotoxic effects of the antiviral drugs rimantadine and polyrem
      were studied on the cultures of some mammalian cells. The results of short-term
      (2 h) exposures with the drugs tested were close to their LD50 values in mammals,
      which makes the proposed test system promising for the assessment of drug
      toxicity in vivo for the whole organism. A study of the state of cell metabolism
      after a long-term (48 h) exposure showed that the system of endocytosis is more
      sensitive than other indices with respect to antiviral drugs. Is was demonstrated
      on the cell level that the binding of drugs into polymeric complexes can decrease
      the degree of its cytotoxicity: the toxicity of polyrem (a polymeric complex of
      rimantadine) was lower as compared to that of the equimolar concentration of
      rimantadine or a mixture of rimantadine with a polymeric carrier.

PMID- 16579065
TI  - [Thermoprotector properties of a combination of sydnocarb with ladasten].
AB  - Thermoprotector properties of a 1 : 1 combination of sydnocarb and ladasten (both
      in a dose of 10 or 20 mg/kg) along with its effect on the hemodynamics and
      respiration in experimental animals were studied. The combination of sydnocarb
      (20 mg/kg) and ladasten (20 mg/kg) produced a significant thermoprotector effect,
      enhanced the regional and local cerebral flow, and increased the respiration
      rate.

PMID- 16579067
TI  - [Anti-malarial vaccination today].

PMID- 16579066
TI  - [Effect of MAGNE-B6 on the clinical and biochemical manifestations of the
      syndrome of attention deficit and hyperactivity in children].
AB  - MAGNE-B6 was used for the therapy of a group of 31 children aged from 6 to 12
      with attention deficiency and hyperactivity syndrome. The control group included
      20 children with similar manifestations of the same pathology, which received a
      polyvitamin complex. The efficacy of therapy was assessed in the 30th day with
      the aid of a complex clinical-neuropsychological and biochemical investigations.
      It was established that the administration of MAGNE-B6 led to improvements in the
      behavior, decreased the level of anxiety and aggression, improved both large- and
      small-scale mobility, decreased the level of synkinesis, increased the
      characteristics of attention, corrected the magnesium homeostasis, and favored
      normalization of the blood electrolytes. Reliable differences (p < 0.01 or 0.001)
      between the test and control groups in the degree of expression of the indicated
      disorders were observed.

PMID- 16579068
TI  - Development of new drugs for chemoprophylaxis of malaria.
AB  - When U.S. troops first encountered drug resistant malaria during the Vietnam war,
      the United States Army responded by establishing a malaria drug research program.
      In 1988, the Walter Reed Army Institute of Research developed mefloquine (WR
      149240) and halofantrine (WR 171669). Actually in association with SmithKline
      Beecham, the WRAIR is developing tafenoquine (WR 238605), an analogue of
      primaquine, which is expected to be effective in both preventing and treating
      malaria in deployed military personnel. Final phase III studies leading to U.S.
      Food and Drug Administration approval are planned for 2000. Applied research is
      also carried out with the association atovaquone-proguanil (Malarone) or with
      azithromycin, but also with primaquine, the associations paludrine-dapsone or
      lapudrine-dapsone, analogues of floxacrine (WR 243251), and a guanylhydrazone (WR
      182393). The future scientific directions must focus on basic and applied
      research for a better understanding of the modes of action and mechanisms of
      resistance to standard and developmental drugs. Using new techniques, the design
      and synthesis of new drugs would hopefully result in the development of drugs
      that circumvent the malaria parasites elusive mechanisms of drug resistance.

PMID- 16579069
TI  - [Which prophylaxis for the travelling child?].
AB  - Protection against malaria can never be totally effective: chemoprophylaxis may
      not prevent infection with multidrug-resistant Plasmodium. Drug tolerance may
      vary. Antimalarial drugs are often not well adapted for infants. Mechanical
      prophylaxis is essential in childhood: devices as insecticide impregnated bednets
      or repellents are the most efficient protection against mosquito bites and in
      fine against infection.

PMID- 16579070
TI  - [Side effects of chemoprophylaxis: real or imagined?].
AB  - Prescribing chemoprophylaxis against malaria is a medical act which is often
      controversial. The choice of appropriate molecule depends on destination, length
      of stay and tolerance to a given product. This latter aspect is difficult to
      evaluate. Among the three most commonly used drugs for malarial prevention-
      Savarine, Lariam and doxycycline--the first enjoys the reputation of being well
      tolerated, the second is perceived as being poorly tolerated and the third,
      little used until now, is suspected of serious complications. It is impossible to
      say by reviewing the available literature, which of these three molecules is
      indeed the least well tolerated, but the studies have followed heterogeneous
      evaluation methods. We propose that the various scientific associations concerned
      by the issue draw together an information sheet on side effects so as to
      encourage practioners to investigate all cases of intolerance of antimalarial
      drugs.

PMID- 16579071
TI  - [Exceptions to malaria chemoprophylaxis for the traveller].
AB  - With the increasing development of international travel, the administration of
      malaria chemoprophylaxis has become very common; however, the pertinence of this
      prescription may in many cases be questioned. All the available drugs,
      particularly the more recent ones, for preventing chloroquine-resistant
      Plasmodium falciparum malaria, can induce adverse effects. Thus, it is better to
      avoid chemoprophylaxis when not absolutely necessary. It should be remembered
      that in many tropical and subtropical countries malaria does not occur at all and
      in others, the level of transmission is insignificant or low. On the other hand,
      in the regions with a high rate of transmission, lack of chemoprophylaxis can be
      justified only by extremely brief, repeated exposures (e.g. aircrew). When
      travelling without chemoprophylaxis to an area with malarial transmission, even
      at minimal level, one must (i) use rigorous antivectorial prophylaxis, (ii) call
      immediately to mind the diagnosis of malaria in the case of unexpected febrile
      illness, and (iii) be in possession of a stand-by treatment if there is no access
      to emergency advice.

PMID- 16579072
TI  - [Pleading for insecticide treated nets in malaria control programmes].
AB  - Insecticide Treated Nets (ITNs) represent for Malaria Control Programmes an
      important and efficacious tool for decreasing malaria incidence. In a large
      number of countries outside Africa, where in most cases malaria is unstable or
      the risk of epidemics is high, the long-term efficacy of ITNs is widely accepted.
      However, it is unclear whether this applies to situations where transmission is
      intermediate or intense. Comparisons of epidemiological data from areas with
      different transmission levels led to contradictory results in terms of the long
      term impact of ITNs in Africa. Besides the methodological problems, these
      comparisons do not take into account the mortality indirectly linked to malaria
      and the time distribution of infective bites. This discussion helps in drawing
      attention to the possible risk of shifting mortality and morbidity to older age
      groups. Although an increased incidence of cerebral malaria cannot be ruled out
      in areas of intense transmission, the overall impact will probably be beneficial.
      These non-conclusive comparisons should not slow down the implementation of ITN
      programmes. The first report on the long-term effect of ITNs contradicts the more
      pessimistic predictions. Simply reducing the transmission peaks could
      substantially decrease malaria mortality and morbidity The improvement of the
      distribution and re-impregnation systems should make ITNs more operational.

PMID- 16579073
TI  - [Limits of impregnated bednets for malaria control in tropical Africa].
AB  - There is no direct relationship between malaria transmission intensity and the
      burden of the disease. Due to acquired immunity there is little difference both
      in potential malaria mortality and the total number of malaria attacks over an
      entire lifetime between individuals bitten by infected anophelines a few times a
      year and those bitten by infected anophelines hundreds of times a year: It is
      only for low levels of transmission that there exists a relation between the
      entomological inoculation rate, the disease incidence rate and potential malaria
      mortality. Even if impregnation by insecticides improves bednet efficiency the
      vector capacity of Anopheles gambiae, An. arabiensis and An. funestus is too high
      for impregnated bednets to be an efficient means of malaria control in most rural
      areas of tropical Africa. The reduction of malaria mortality observed during
      several pilot projects is probably a short term effect. We propose focussing
      vector control on low and/or unstable malaria transmission areas, i.e. where
      these activities have proved crucial for the reduction or even eradication of
      malaria. In moderate or high transmission areas, better access to health care and
      improvement of malaria case management are currently the only means for reducing
      durably the burden of malaria.

PMID- 16579075
TI  - [In vitro susceptibility of 232 isolates of Plasmodium falciparum to
      antimalarials in Burkina Faso (West Africa)].
AB  - Plasmodium falciparum in vitro susceptibility to chloroquine, quinine, mefloquine
      and halofantrine was investigated in patients living in Bobo-Dioulasso (Burkina
      Faso, West Africa). Our study was carried out from July to November 1997 at the
      Malaria Chemoresistance Reference Centre, Centre MurazIOCCGE. Inclusion criteria
      were: presence of a single infection by R falciparum with a parasite count > or
      =4000 infected red cells/mm3. The susceptibility to drugs was measured after an
      incubation period of 48 hours at 37 degrees C, under 5% CO2. (3H) Hypoxanthine
      was added to the medium to monitor parasite growth. 134 isolates of P. falciparum
      were tested against chloroquine; 24.6% (33/134) were resistant. We have also
      documented 11.2% (15/133) of resistant isolates to halofantrine. All the tested
      isolates were susceptible to quinine (n=135) and mefloquine (n=136). A
      significant positive correlation was found between the following IC50 values:
      chloroquine-quinine, quinine-mefloquine and mefloquine-halofantrine. Our study
      shows no significant increase of the prevalence of chloroquine-resistant strains
      of P. falciparum in our study area; as well as the persistence of resistance to
      halofantrine with regard to previous publications in the subject.

PMID- 16579074
TI  - [Allelic polymorphism of Plasmodium falciparum MSP-2 gene in blood samples from
      Gabonese children].
AB  - In this study we have undertaken the molecular analysis of the MSP-2 gene of R
      falciparum isolates collected from schoolchildren living in the village of Dienga
      (Gabon). Using conventional microscopy and the polymerase chain reaction, 61% of
      these children harboured parasites without any symptom of malaria (asymptomatic
      status). Children with a malaria episode were those with an axillary temperature
      > or = 37.5 degrees C and a parasitaemia > or =800 parasites/microl of blood.
      Comparisons of the allelic diversity and distribution of MSP-2 gene were carried
      out according to the clinical status at the time of sampling. Polymorphism of the
      MSP-2 gene was large in both clinical groups, both asymptomatic and symptomatic
      (11 identified alleles). The allele FC27/560bp (base pairs) was found
      significantly in clinical isolates. Prevalence of the 3D7 family was 68% and 44%
      in asymptomatic infections and clinical infections, respectively. Multiple P.
      falciparum genotypes were more predominant in clinical cases (2.96 clones/child
      with a malaria attack vs 2.01 clones/child with asymptomatic infections). We
      observed also a reduction of the complexity of infection beyond the age of 10
      years. These results are discussed in regard to studies conducted in other areas
      in Africa.

PMID- 16579076
TI  - [Malaria prevalence survey in 24 Guinean villages in the Kindia area].
AB  - The authors report the results of a survey of malaria prevalence carried out from
      October to December 1998 in 24 villages located upstream of the Garafiri dam, in
      the Kindia area. The parametre used for the assessment of prevalence was the
      Plasmodium index. The gametocyte and spleen indexes were also recorded. The
      prevalence observed (34,7%) confirms the presence in this area of stable malaria
      mostly transmitted by Anopheles gambiae in tropical Africa. This prevalence rate
      is compatible with the epidemiological data of the Ministry of Health.

PMID- 16579077
TI  - [No influence of season of transmission nor age of patients on the complexity and
      genetic diversity of Plasmodium falciparum infection in Cotonou, Benin].
AB  - The aim of the present study was to determine the genetic diversity and allelic
      frequencies of the genes encoding for the merozoite surface protein-1 (MSP-1) and
      protein-2 (MSP-2) of P. falciparum collected from Beninese patients during the
      high and low transmission seasons in Cotonou, in South Benin. Sixty and twenty
      four patients were sampled during the dry and wet seasons, respectively Parasite
      DNA was analysed using allele-specific primers to amplify block2 of MSP-1 and
      central variable region of MSP-2. A total of 12 (K1, Mad20, Ro33) MSP-1 and 23
      (3D7, FC27 and hybrids) MSP-2 alleles were detected. Neither age nor transmission
      season modified the genetic diversity of P. falciparum nor the distribution of
      MSP-1 and MSP-2 alleles. Combining the results of MSP-1 and MSP-2 genotyping,
      multiple P. falciparum infections were observed in 57% and 70% of isolates during
      the wet and dry seasons, respectively. The complexity of infections defined as
      the number of parasite genotype per isolate was 2.4 and it was not affected
      either by the season or by the age of the host. We conclude that change of season
      did not influence the permanent turn-over of parasites and the complexity of
      infections. Data obtained here will serve as a baseline for future studies, such
      as the impact of malaria control measures on parasite populations, to be
      conducted in Cotonou.

PMID- 16579078
TI  - [Contribution to the study of mosquitoes (Diptera: Culicidae) of Guinea: Fauna
      and distribution].
AB  - The authors report the results of ten years of entomological research conducted
      in Guinea. During this period, 84,000 larvae and 66,000 adult mosquitoes
      belonging to 8 different genera were captured and identified according to species
      or species groups. Mosquito fauna in Guinea includes almost all the known vectors
      of malaria and filaria in West Africa (see tables I-IV) as well as many of the
      known vectors of arboviruses. Four methods were used for capturing the insects,
      the most efficient being the use of a net in vegetation which succeeded in
      trapping 83% of the species described.

PMID- 16579079
TI  - [Malaria vector control in Cameroon: past, present, future. Reflections].
AB  - During the fifties, large scale malaria vector control projects based upon house
      spraying were implemented in Southern and Northern parts of Cameroon in line of
      malaria eradication concept. In the South, the pilot zone of Yaounde gathered
      about 150,000 inhabitants, in the forest area. First operations started in 1953
      but the programme became actually operational in 1956. It was divided in two
      parts: the western part was treated with DDT, while the eastern one was treated
      with dieldrin. At the same time, the whole forested area was also treated with
      dieldrin until 1960. Yaounde itself was not treated because it was free of
      anopheles and malaria. House spraying in the pilot area of Yaounde was a complete
      success and plasmodic index dropped below 1%. The same success was observed in
      most of the southern treated areas. Unfortunatly dieldrin resistance of An.
      gambiae hampered this programme which stopped in 1960. The northem pilot project
      dealt with some 250,000 inhabitants around Maroua, in a savanna area. To avoid
      dieldrin resistance observed in 1956, DDT was selected and house spraying started
      in 1959. From a strictly operational point of view, the campaign was considered
      as a success. But after two years, it was noticed that plasmodic index remained
      still around the same value of 35% and the programme stopped. It was thus stated
      that according to available techniques it was not possible to reach the ultimate
      goal of eradication even when chemoprophylaxis (chloroquin + pyrimethamin) was
      added. The comparison between south (= success) and north (= failure) was very
      interesting as it underlined the big differences between epidemiological faces,
      an unaccepted concept at that time. Now ecological and epidemiological diversity
      is the well acknowledged. It also underlined the need of diversity of strategies
      according to the epidemiology of the disease and the ecology of its vector Vector
      control was then stopped for a while. In the eighties, Primary Health Care was
      promoted and malaria control shifted from vector to parasite control, vector
      control remaining as a prevention method. But chemioresistance of Plasmodium
      falciparum appeared and. quickly spread, at different levels, across the country.
      A new emphasis was therefore given to vector control thank to the newly developed
      technique of insecticide impregnated mosquito nets. Two kinds of studies were
      undertaken: - what people were actually doing in term of mosquito control at
      family level, the main reason and the costs as well as current use of mosquito
      nets - the efficacy of pyrethroid treated mosquito nets (IMN) in different areas
      of southern forested area against different malaria vectors: An. gambiae, An.
      nili, An. moucheti. It thus clearly appeared that IMN were very successful in
      sharply reducing malaria transmission aAd morbidity. But its promotion is limited
      by the current poor use of mosquito nets in Yaounde (1 mosquito net for 27
      "beds") while in Douala, where IMN are largely used against the bite of the huge
      population of Culex. quinquefasciatus, the implementation of the first riational
      centre for impregnation of mosquito net was a great success, as long as it was
      headed by a motivated and skill manager Impregnated mosquito nets appear thus as
      a tool of great efficacy but their sustainability is still matter of concern and
      promotional campaigns must be developed involving private and public, political
      and scientific spheres as well as the general population who should be encouraged
      to become partners and even actors of vector and malaria control at their
      household level.

PMID- 16579080
TI  - [Feeding behaviour of Anopheles funestus resting females in Senegal].
AB  - The feeding behaviour of An. funestus resting females was studied in eleven sites
      in Senegal along a west-east transect in two biogeographical zones (the Sudanese
      and Sudanese-Guinean zones) by an ELISA technique. Mosquitoes were collected by
      pyrethrum spray catches. For the 1563 blood meals tested, the main hosts were
      humans, cows, sheep and horses representing respective proportions of 85%, 9.9%,
      1.3% and 3.8%. No blood meal was taken on chicken. The percentage of non-reacting
      blood meals was 2.6%. A heterogenity of feeding behaviour was observed in the
      sample locations. The anthropophilic rates were higher in the northern Sudanese
      zone as versus the southern Sudanese and Sudano-Guinean zones.

PMID- 16579081
TI  - Sixty-one cases of angina pectoris due to coronary heart disease treated by
      external use of the paste of nitrum and realgar powder on zhiyang (GV 9).
AB  - In order to inquire into the therapeutic effects of Xiao Shi Xiong Huang San (the
      Nitrum and Realgar Powder), one of the Dunhuang Prescription, on angina pectoris
      due to coronary heart disease (APCHD), the authors have treated 61 cases of APCHD
      by externally applying paste of the powder on Zhiyang (GV 9), with another 30
      cases of APCHD treated with the nitroglycerin paste on Zhiyang as the controls.
      The results showed that the total effective rate was 82% and markedly effective
      rate 31.2% in the treatment group (the Paste of Nitrum and Realgar Powder), and
      the total effective rate was 46.6% and markedly effective rate 23.2% in the
      control group (the nitroglycerin paste). The difference in therapeutic effects
      between the two groups was very significant (P<0.01), indicating that the
      therapeutic effect of the former was significantly superior to that of the
      latter.

PMID- 16579082
TI  - Jian Nao Ning for treatment of memory impairment in patients with mild or
      moderate multi-infarct dementia.
AB  - Forty patients with multi-infarct dementia (MID) were randomly assigned to the
      treatment group (25 cases) treated with Jian Nao Ning (JNN) and the duxil control
      group (15 cases). Memory function were assessed at baseline and endpoint using
      memory subscales of a battery of New Psychometric Tests (Chinese version)
      including mini-mental state examination (MMSE), verbal memory, and non-verbal
      memory, etc. After treatment, the mean scores of verbal memory in the Hopkins
      Verbal Learning Test (P<0.05) and total memory scores of memory items (P<0.001)
      in JNN group increased significantly; and improvement in episodic memory function
      including story recall (immediate and delayed), delayed word recall, verbal
      learning and verbal recognition and visual recognition in the JNN group was
      better than that in the duxil control group, suggesting that JNN can obviously
      improve memory function for the patients with mild or moderate multi-infarct
      dementia.

PMID- 16579083
TI  - TCM treatment of rheumatoid arthritis by supplementing the kidney and
      invigorating the blood circulation.
AB  - The therapeutic effects in treating the intermediate and late rheumatoid
      arthritis by supplementing the kidney and invigorating blood circulation were
      observed. In the 43 cases of the treatment group, No. 2 Qu Feng Shi Ling capsules
      and Fenbid were prescribed, while in the 39 cases of the control group Lei Gong
      Teng Tablets and Fenbid were given. The results showed that the total effective
      rate in the treatment group was more satisfactory than that in the control
      (P<0.05 or P<0.01). With less toxic effects, the former could better improve the
      local swelling and lower the blood viscosity.

PMID- 16579084
TI  - Clinical observation on influence of chinese medicines for promoting blood
      circulation to remove blood stasis on FIB and DD in plasma of patients with
      cerebral thrombosis.
AB  - OBJECTIVE: to study the influence of Chinese medicines for promoting blood
      circulation to remove blood stasis on fibrinogen (FIB) and D-dimer (DD) in plasma
      of patients with cerebral thrombosis. METHOD: 73 inpatients with acute cerebral
      thrombosis were randomly divided into a control group of 34 cases and a treatment
      group of 39 cases. The content of FIB and DD in plasma was detected before
      treatment and on the 7th and 14th days after treatment. RESULT: FIB content in
      plasma after treatment was lower than that before treatment in the control group
      (P<0.01) and more remarkable in the treatment group (P<0.001). There was an
      obvious difference in DD content before and after treatment in both groups. DD
      content on the 7th and 14th days after treatment in the treatment group was
      obviously higher than that in the control group (P<0.01 and P<0.05 respectively).
      CONCLUSION: Chinese medicines for promoting blood circulation to remove blood
      stasis can reduce the FIB content in plasma of patients with cerebral thrombosis,
      raise the DD content in plasma, cause the peak of DD content appear earlier and
      obviously improve hypercoagulability of blood in patients with cerebral
      thrombosis.

PMID- 16579085
TI  - TCM treatment of 18 cases of sicca syndrome with the heat-removing and dampness
      eliminating method.

PMID- 16579086
TI  - Treatment of irritable bowel syndrome by oral administration of Chinese medicines
      and retention-enema--a report of 50 cases.

PMID- 16579087
TI  - Treatment of motor neuron disease with qi-invigorating herbs--a report of 31
      cases.

PMID- 16579088
TI  - Pricking, cupping and qu feng tiao ying decoction for treatment of chronic
      urticaria.

PMID- 16579089
TI  - Acupuncture treatment of vomiting caused by chemotherapy.

PMID- 16579090
TI  - Acupuncture treatment of depressive syndromes after cerebral vascular accidents.

PMID- 16579092
TI  - Warm needling and blood letting for treatment of gonitis.

PMID- 16579091
TI  - Clinical observation on intractable insomnia treated by point pressure in 42
      cases.

PMID- 16579093
TI  - Clinical observation on 100 cases of postoperative pain of anal-intestinal
      diseases treated with vitamin K blocking at changqiang point.

PMID- 16579094
TI  - Ear acupuncture therapy for 37 cases of dysmenorrhea due to endometriosis.

PMID- 16579095
TI  - Treatment of functional retrograde ejaculation with acupuncture and TCM herbal
      drugs.

PMID- 16579096
TI  - Clinical experience in application of the point wangu.

PMID- 16579097
TI  - Clinical application of the point taichong.

PMID- 16579098
TI  - Clinical experience in application of the point zhongzhu.

PMID- 16579099
TI  - Therapeutic actions of the Chinese herbal formulae with cold and heat properties
      and their effects on ultrastructures of synoviocytes in rats of the collagen
      induced arthritis.
AB  - The therapeutic actions of Qing Luo Yin with heat property and Wen Luo Yin with
      cold property on pain, swelling of the ankle, arthritis index and ultrastructures
      of synoviocytes were compared in rats of type II collagen-induced arthritis
      (CIA), with tripterygium glycosidorum (TG) used as control. The results indicated
      that both QLY and WLY could reduce pain, swelling of the ankle and the arthritis
      index of CIA, and QLY had better effects in reducing the swelling of the ankle
      and controlling the secondary pathological lesions as compared with WLY.
      Investigation on the ultrastructures of synoviocytes indicated that both QLY and
      WLY could reduce the number of Golgi apparatus, rough surface endoplasmic
      reticulum, dense bodies, matrix filaments and vacuoles so as to suppress the
      excessive secretion of synoviocytes in rats of CIA.

PMID- 16579100
TI  - Advances in TCM treatment of gastric cancer and studies on the apoptosis.

PMID- 16579101
TI  - Acupuncture treatment of abdominal pain.

PMID- 16579103
TI  - Accountability addressed. AHA confers with Grassley on charity-care proposals.

PMID- 16579102
TI  - Clinical experience in TCM treatment of chronic cervicitis.

PMID- 16579104
TI  - Limited service maximum fuss. Specialty hospital issue has caught the attention
      of senators as a physician-owned Oregon facility fights for its Medicare status.
AB  - The battle over specialty hospitals got more bruising last week, with two
      powerful senators seeking more oversight data, and a hospital that's become a
      symbol of the controversy fighting for its life. The AMA's William Plested, left,
      says the problem isn't specialty hospitals, but how hospitals are paid. "The way
      all payments are figured makes winners and losers," he says, noting for-profits
      contribute to communities through taxes.

PMID- 16579105
TI  - No more data sales. JCAHO will offer free quality data as 'public utility'.

PMID- 16579106
TI  - Improving QIOs. Control of regulatory role at center of debate.

PMID- 16579107
TI  - Few details on DRG revamp. The CMS may reveal portions of new system in April.

PMID- 16579108
TI  - Efforts to regulate GPOs continue. Senate hearing will discuss business
      practices, payments.

PMID- 16579109
TI  - Trinity ready to exit managed care. Big Catholic system is considering selling
      subsidiary as part of streamlining.

PMID- 16579110
TI  - Hospital sued over split. Parent doesn't want Christ Hospital to leave the fold.

PMID- 16579111
TI  - Nurse-ratio fight goes national. Ill., Mass., now targeted for Calif. staffing
      standards.

PMID- 16579112
TI  - Leave the herd behind. Avoid the groupthink on mergers that caused higher prices,
      lowered quality.

PMID- 16579113
TI  - The efficiency equation. Determining how to measure healthcare performance--and
      other first steps.

PMID- 16579114
TI  - Built-in benefits. Annual Construction & Design Survey shows spending remains
      strong; patient-safety focus, 'sustainable design' among noteworthy trends.

PMID- 16579115
TI  - View from the country. Rural healthcare lobbyist pushes policymakers, legislators
      to understand effects of their proposals on nonurban providers.

PMID- 16579116
TI  - Doc turnover rate falls: study. Most believe trend will continue in next two
      years.

PMID- 16579117
TI  - Expanding perioperative nursing knowledge.

PMID- 16579118
TI  - Why is it always nurses who ask "why?".

PMID- 16579119
TI  - Reap the benefits of writing for publication.

PMID- 16579120
TI  - Microbial flora on operating room telephones.
AB  - Approximately 500,000 surgical site infections (SSIs) occur each year in the
      United States. The purpose of this study was to determine if the bacteria most
      frequently involved in SSIs could be found on telephones in the OR. Twenty-six
      cultures were taken from telephones in 14 ORs and two substerile rooms at a large
      teaching medical center. Using standard laboratory procedures, the researchers
      identified coagulase-negative staphylococci in the cultures. The study found that
      telephones in the OR can serve as reservoirs for SSI-causing bacteria.

PMID- 16579121
TI  - Evolution of robotics in surgery and implementing a perioperative robotics nurse
      specialist role.
AB  - Use of robotics is expanding rapidly in the medical arena. Not only are a growing
      number of facilities purchasing robotic systems, but the number of surgeons using
      them also is increasing, which creates many challenges (eg, cost, training,
      safety). The evolution of robotics in surgery is presented within the context of
      virtual reality, telepresence, telemanipulation, and passive (ie, master-slave)
      robotic surgical systems. A new perioperative nursing role, the robotics nurse
      specialist, was developed and implemented at one facility. The need for a
      robotics nurse specialist and how this role can help the entire surgical team
      promote positive patient and facility outcomes also is discussed.

PMID- 16579122
TI  - Electrosurgical burns in pediatric patients undergoing liver resection with
      saline-enhanced radiofrequency technology.
AB  - Use of saline-enhanced radiofrequency (RF) technology reduces blood loss in
      infants undergoing liver resection. Radiofrequency systems continuously deliver
      much higher currents for longer periods of time than conventional coagulation
      instruments and thus increase the risk of complications. Thress infants
      undergoing liver resection with the newer RF technology at one facility
      experienced electrosurgical unit (ESU) dispersive pad burns. As a result, an
      experiment was performed on animal subjects to determine best ESU dispersive pad
      placement on infants and to gather data on device impedance. Recommendations to
      prevent burns include central placement of the ESU dispersive pad and activating
      warming devices only after resection is complete.

PMID- 16579123
TI  - Evaluating use of flash sterilization in the OR with regard to postoperative
      infections.
AB  - This article describes a quality improvement project that examined postoperative
      infection rates for 100 surgical procedures in which a total of 121 flash
      sterilizations were performed and determined the costs of treating the
      postoperative infections compared to the cost of purchasing additional
      instruments. The post operative infection rate on physical examination was 3%,
      and the overall cost of diagnosing and treating the postoperative infections was
      found to be lower than the cost of purchasing additional instruments. To minimize
      use of flash sterilization, the hospital has added additional surgical instrument
      inventory and expanded flash sterilization education requirements for staff
      members.

PMID- 16579124
TI  - Recommended practices for traffic patterns in the perioperative practice setting.

PMID- 16579125
TI  - Recommended practices for the care and handling of specimens in the perioperative
      environment.

PMID- 16579126
TI  - Recommended practices for sterilization in the perioperative practice setting.

PMID- 16579127
TI  - A matter of degree.

PMID- 16579128
TI  - Medicare reimbursement in the surgical suite.

PMID- 16579129
TI  - Medication diversion in the perioperative setting.

PMID- 16579130
TI  - Lifting the lid off of pricing. With HHS moving to post what it pays for common
      procedures, the debate over healthcare pricing transparency is heating up.
AB  - Healthcare pricing was the focus of discussion in Washington last week, with HHS
      announcing agencies will be posting the prices paid for common procedures, and
      industry experts testifying at a hearing on the topic. The debate among lawmakers
      tends to mask the complexity of shifting healthcare costs, says Paul Ginsburg,
      left.

PMID- 16579131
TI  - Spreading the good news. Community-benefit workers gain higher profile.

PMID- 16579132
TI  - GPO hearing inconclusive. Senators wait for response on bills to tighten
      regulation.

PMID- 16579133
TI  - Payment changes debated. LTCHs worry that payment levels will be too low.

PMID- 16579134
TI  - AHA blasts staffing standards. JCAHO's proposed changes 'lack clarity and
      precision'.

PMID- 16579135
TI  - Flu planning crucial: experts.

PMID- 16579136
TI  - 100K Lives falling short. IHI's patient-safety campaign expected to save 61,000.

PMID- 16579137
TI  - Sutter expands building plans.

PMID- 16579138
TI  - More charity-care scrutiny. Kansas joins states investigating billing practices.

PMID- 16579139
TI  - Partnering in Montana. Not-for-profit insurers will share overhead costs.

PMID- 16579140
TI  - A bottom-line debate. Opposition to doc-owned hospitals comes down to money.

PMID- 16579141
TI  - A transparency guide. The things not-for-profits need to do to keep their tax
      exemptions.

PMID- 16579142
TI  - Trustees of the Year 2006. Whatever needs to be done.

PMID- 16579144
TI  - New life for dead zones. Devices applications boost reliability, capability of
      wireless systems in healthcare settings.

PMID- 16579143
TI  - Trustees of the Year 2006. A knack for building consensus.

PMID- 16579145
TI  - A watchful eye.

PMID- 16579146
TI  - A self-abuser says support and understanding can save lives.

PMID- 16579147
TI  - An experienced RN remembers what nursing is really all about.

PMID- 16579148
TI  - Nurses speak out on voting for their manager.

PMID- 16579149
TI  - Nurses speak out on voting for their manager.

PMID- 16579150
TI  - Nurses speak out on voting for their manager.

PMID- 16579151
TI  - Nurses speak out on voting for their manager.

PMID- 16579152
TI  - What steps is your facility taking to hire or retain nurses in light of the
      nursing shortage?

PMID- 16579153
TI  - Your guide to safe transfusions.

PMID- 16579154
TI  - Quality, performance measures make haste, slowly.

PMID- 16579156
TI  - A new weapon to combat stroke.

PMID- 16579155
TI  - ED in teenagers: it's not necessarily psychological.

PMID- 16579157
TI  - Would you suspect this skin-eating infection?

PMID- 16579158
TI  - Drug watch 2006: new frontiers.

PMID- 16579159
TI  - Save time! Do a 5-minute initial assessment.

PMID- 16579160
TI  - Is it more than just stress?

PMID- 16579161
TI  - Reward loyalty.

PMID- 16579162
TI  - [Vulvar intraepithelial neoplasm].
AB  - BACKGROUND: Vulvar intraepithelial neoplasia is a challenge for the physician as
      it is asymptomatic and it can evolve to malignant disease. A high suspicion
      index, as well as some biopsies are necessary, provided an early invasive disease
      can exist. OBJECTIVE: To establish the patient's characteristics with vulvar
      intraepithelial neoplasia, seen at the Clinica de Especialidades de la Mujer,
      SEDENA. PATIENTS AND METHODS: An observational and retrospective analysis was
      done from February 1st, 1990 to December 31st, 2004. We used the data base of the
      Hospital Central Militar and of the Clinica de Especialidades de la Mujer,
      SEDENA. We identified patients with vulvar intraepithelial neoplasia or in situ
      vulvar cancer diagnosis. We assessed the following variables: patient's age,
      intraepithelial neoplasia or history of cervical cancer, acuminated vagina or
      condylomas, prescribed treatment and current health state. RESULTS: We identified
      38 patients with ages between 49 and 82 years old. Patients with intraepithelial
      neoplasia I were the youngest, except one, whom at the moment of the diagnosis
      had 58 years old. The histopathological diagnosis was of intraepithelial
      neoplasia type I (koilocytotic atypia) in 10 cases, type II in 10 more, and type
      III in 18 of them. CONCLUSIONS: Treatment should be individual for each patient.
      In most of the cases and due to the high recurrence rates we prefer the
      conservative treatments.

PMID- 16579163
TI  - [Thoracoamniotic shunts and thoracocentesis in fetal therapy].
AB  - BACKGROUND: The not heart thoracic anomalies are caused by different
      abnormalities in the embryonic period with similar physiopathologic mechanisms.
      The prenatal treatment by means of decompression can improve substantially the
      clinical results in these patients. OBJECTIVE: To evaluate, in a qualitative way,
      the effect of the thoracoamniotic shunts and thoracocentesis in the perinatal
      outcome in fetuses with not heart thoracic anomalies. METHODS: Twenty-two
      articles were revised describing 308 cases of fetuses with congenital cystic
      adenomatoid malformation (CCAM), 25 cases of hydrothorax and 55 cases of
      broncopulmonary sequestration (BPS). We analyzed the adverse prognostic factors
      that indicated the treatment election in uterus as well as complications and
      perinatal outcome. RESULTS: Of the 388 cases of not heart thoracic anomalies, 250
      fetuses were managed conservatively, and in 102 fetuses handling in uterus was
      started. Hydrops was identified as the worst prognostic factor to these fetuses,
      with a survival rate of 55.7%. The global survival was of 56.5% (155 cases) in
      the fetuses with CCAM, 98.1% (52 cases) in the fetuses with BPS and of 80% (20
      cases) in the fetuses with hydrothorax. CONCLUSIONS: When having a fetus with
      some of these pathologies, it should be evaluated in an individual and integral
      way; according to the gestational age when diagnosed, as well as the type of
      lesion and the presence or absence of fetal dropsy to decide between fetal
      therapy or expectant handling.

PMID- 16579164
TI  - [Associated factors to abnormal glucosylated hemoglobin in the postpartum
      period].
AB  - OBJECTIVE: To demonstrate the association between risk factors and abnormal
      glucosylated hemoglobin detected in women during the postpartum period. PATIENTS
      AND METHODS: A case and control study was carried out at the Hospital Civil de
      Guadalajara Dr. Juan I. Menchaca during six months. Glucosylated hemoglobin and
      glucose concentration from 160 fasting women with a pregnancy > or =28 weeks was
      obtained during the postpartum period. With an odds ratio and confidence interval
      (95%) the epidemiological meaning of risk factors was identified. RESULTS: The
      abnormal glucosylated hemoglobin was significantly associated to: single,
      separated and divorced women (p < 0.05); major frequency of previous caesarean
      (OR: 2.78, IC 95%:1.25-6.22), p = 0.006, and higher proportion of children with
      congenital malformations (OR: 12, IC 95%: 1.38-104), p = 0.01. In the group cases
      48% of caesareans was associated to probable gestational diabetes: moderate
      preeclampsia, eclampsia, fetal macrosomy, and preterm deliveries. CONCLUSION: It
      is necessary to make an early detection of risk factors associated to abnormal
      glucosylated hemoglobin and to prevent adverse effects as congenital
      malformations and clinical complications that increase the incidence of
      caesarean.

PMID- 16579165
TI  - [Prevalence and clinical-urodynamic characteristics of vesical voiding
      dysfunction in two urodynamic centres].
AB  - BACKGROUND: It has been estimated in English medical reports, that the frequency
      of vesical voiding dysfunction in urogynecological patients is around of 22-24%;
      however in our country it does not have any published epidemiological study about
      this problem. OBJECTIVE: To detect the prevalence of vesical voiding dysfunction
      in our urodynamic unities and describe the clinical and urodynamic findings.
      MATERIAL AND METHODS: This is a descriptive and retrospective study in which were
      revised the clinical reports of 300 female patients, that were sent to some of
      our urodynamic units because they were suffering of lower urinary tract symptoms.
      Assessment variables included: Patient clinical history, physical examination,
      urinalysis, urine culture, urethral calibration, Q tip test, urethrocistoscopy,
      uroflowmetry, multichannel cystometry, electromyography and pressure voiding
      study. The diagnosis criterion was based in the concept that Blaivas established
      for vesical voiding dysfunction in women. RESULTS: The diagnosis of vesical
      voiding dysfunction was established in 72 cases of the total 300 patients
      analyzed. The most frequent symptom was the irritative vesical type
      (frequency/urgency), following of weak stream. Some grade of pelvic organ
      prolapse was detected in 84.8% of cases. Uroflowmetry was normal in 50% of the
      cases; nevertheless in the morphologic aspect were observed profile signs
      suggestive of distal vesical obstruction in 75%, and detrusor hypoactivity in 25%
      of the total of the cases. CONCLUSIONS: The frequency of obstruction in our
      casuistic was similar to the other authors. The obtained results permit us to
      confirm that the vesical voiding dysfunction in the urogynecological Mexican
      patients is a frequent problem in the urogynecological patient; however the
      diagnostic is complex and require a carefully correlation as clinical as
      urodynamical aspects in addition to endoscopic and image studies.

PMID- 16579167
TI  - [Risk factors associated to ovarian cancer].
AB  - OBJECTIVE: To determine the risk factors associated to ovarian cancer. PATIENTS
      AND METHODS: A case-control study was carried out including 31 women with ovarian
      cancer and 69 patients with benign ovarian tumors corroborated with a
      histopathological study. We analyzed 26 independent variables, which
      classification was clinic, sociodemographic and ultrasonographic. The dependent
      variable was ovarian cancer, and it was assigned a value of 1 if it was present
      and 0 if it was absent. The statistical analysis was done using a logistic
      regression analysis, with an alpha value of 0.05. RESULTS: The malignant tumor of
      epithelial cells was the most common histological variety and was seen in 22
      cases (71%). There were 24 cases (77.4%) in clinical stage I at the time of the
      diagnosis. Out of the 26 studied variables late menarche (p = 0.02), multiparity
      (p = 0.02), loss of weight (p = 0.04), solid tumor (p = 0.02), mixed tumor (p =
      0.02) and irregularities of the tumor (p = 0.03) were significant in the applied
      model. CONCLUSIONS: The sociodemographic variables associated to ovarian cancer
      were: late menarche and multiparity; the clinical significant variable was loss
      of weight; and the ultrasonographic variables were solid tumor, mixed tumor and
      irregularities of the tumor. A population screening program is recommended in
      women who are in reproductive age, and it should include a gynecological
      ultrasonographic scanning in order to make an opportune diagnosis of this
      pathology.

PMID- 16579166
TI  - [Serum levels of IL-1beta, IL-6 and TNF-alpha in infertile patients with ovarian
      dysfunction].
AB  - BACKGROUND: Some cytokines that take part in the ovarian cycle regulation, such
      as IL-1beta, IL-6 and TNF-alpha play an important role during growth and
      development of ovarian follicle. Quantification of some cytokines is promissory
      in the work-up of ovarian reproductive pathology. OBJECTIVE: To determine serum
      levels of IL-1beta, IL-6 and TNF-alpha in infertile patients with ovarian
      dysfunction and to compare them with those found in ovulatory patients. PATIENTS
      AND METHODS: We conducted a cross-sectional study in infertile patients with
      premature ovarian failure, diminished ovarian reserve, chronic anovulation and
      ovulatory patients that were well-characterized by clinical and hormonal
      parameters. We determined serum concentrations of IL-1beta, IL-6 and TNF-alpha by
      an ELISA method. Statistics was conducted by using one way ANOVA, Kruskall-Wallis
      and Pearson correlation analyses. RESULTS: We studied a total of forty patients.
      The mean age was 30 years; we did not find significant differences among groups.
      Overall mean of cytokines concentration was: 13.2 pg/mL for IL-1beta; 8.4 pg/mL
      for IL-6; and 1.5 pg/mL for TNF-alpha. We observed a significant difference in
      the concentration of TNF-alpha in the premature ovarian failure group when it was
      compared to the control group. Pearson correlation coefficients were no
      significant. CONCLUSION: A wide range of dispersion of serum cytokines
      concentration was observed. Serum concentrations of TNF-alpha in woman with
      premature ovarian failure were significantly lower than those in the control
      group. Our findings represent a precedent in the powerful utility of the
      quantification of these cytokines in reproductive medicine.

PMID- 16579168
TI  - [Secondary peritonitis due to rupture of pyometra in cervical cancer].
AB  - Only 8 cases of spontaneous uterine rupture in untreated cervical cancer have
      been reported in the literature. We present the case of a 52-year-old female, who
      was admitted to the emergency room due to hypovolemic shock and signs of
      peritonitis. A 6x4x4 cm cervical tumor was detected at physical exam. At
      laparotomy 2000 mL of purulent material were found and a 1-cm perforation in the
      posterior portion of the uterine segment was identified. A subtotal hysterectomy
      was performed. The patient received antibiotic and support at Intensive Care
      Unit. Finally, the patient presented ascendant flaccid paralysis and died due to
      bronchoaspiration. Spontaneous pyometra rupture in untreated cervical cancer is a
      rare condition and must be considered in postmenopausal women with cervical
      tumors and peritonitis signs.

PMID- 16579169
TI  - [A report of 119 cesarean sections in Social Security of Monterrey. From 1946 to
      1949. 1950].

PMID- 16579170
TI  - Molecular diagnosis of malignant lymphoma: mantle cell lymphoma, anaplastic large
      cell lymphoma, and marginal zone B-cell lymphoma of malt.
AB  - Malignant lymphoma is a heterogeneous category embracing three major types of
      lymphoid neoplasms: B cell neoplasms, T and NK cell neoplasms, and Hodgkin
      lymphoma. Within each type, distinct disease entities are defined based on a
      combination of morphology, immunophenotype, genetic features and clinical
      syndromes, the emphasis on which represents a new paradigm in the lymphoma
      classification of the World Health Organization (WHO). These lymphoma entities
      often have distinctive cytogenetic abnormalities, usually involving
      translocations that place a potential cellular oncogene under the influence of
      the immunoglobulin in some low-grade B-cell lymphomas. Both pathologists and
      oncologists are now concerned with better understanding each disease entity and
      its spectrum of morphology, genetic events, and clinical behaviors. Over the last
      decade, significant progress has been made in the molecular characterizations of
      mantle cell lymphoma, anaplastic large cell lymphoma, and marginal zone B-cell
      lymphoma of mucosa-associated lymphoid tissue (MALT), which have not only
      provided insights into the pathogenesis of lymphomas, but also valuable data that
      could lead to therapies based on their clinical behavior.

PMID- 16579171
TI  - Cellular and systemic defense system against age-promoting stimuli.
AB  - Although much progress has been achieved in aging research using lower animals,
      especially yeast and C. elegans, aging in humans remains puzzling. Here I offer
      my hypothesis of host defense against age-promoting stimuli, which holds that the
      cell itself has a defense system and multi-organism, an even more sophisticated
      one against age-promoting stimuli. Here I review recent achievements in aging
      research and try to explain their findings in the light of my hypothesis. Age
      promoting stimuli, including reactive oxygen species, telomere shortening or
      external stimuli such as UV or radiation induce stress responses in cells. The
      cellular defense system operates to overcome stimuli or repair damaged cellular
      components. Stress-induced damaged cells or infectious stimuli activate systemic
      defense systems, especially the innate immune system. Macrophages in the innate
      immune system are especially active not only in clearing damaged cells and
      repairing damaged tissue, but unfortunately, also in inducing age-related
      diseases.

PMID- 16579172
TI  - Advances in treatment of epithelial ovarian cancer.
AB  - Since most cases of epithelial ovarian cancer are advanced at diagnosis, this
      disease is one of the most lethal malignancies of the female genital tract. In
      recent years, aggressive cytoreductive surgery and chemotherapy have been
      employed in an attempt to improve the survival rate in patients with epithelial
      ovarian cancer. Introduction of platinum anticancer drugs increased survival
      rate, and several randomized studies have been tried to establish the better
      combination of anticancer drugs. As a result, the combination of paclitaxel and
      carboplatin was considered as standard regimen for the first-line treatment of
      patients with advanced ovarian cancer. Since International Federation of
      Gynecology and Obstetrics (FIGO) accepted a postoperative staging system in 1988,
      staging laparotomy needs hysterectomy, bilateral adnexectomy, omentectomy, and
      pelvic and para-aorta lymphadenectomy. However, the influence of lymphadenectomy
      on survival still remains controversial. Complete resection of the tumor is often
      difficult since the disease has spread to the abdominal cavity. In such cases,
      interval debulking surgery is performed after chemotherapy to remove tumors
      completely. The effectiveness of neoadjuvant chemotherapy and interval debulking
      surgery still remains unclear. This review will describe the advances in surgical
      procedures and chemotherapy in treatment of ovarian cancer patients.

PMID- 16579173
TI  - Characteristics of processing for trait adjectives in depressive persons: an
      event-related potential study.
AB  - Event-related potentials (ERP) following emotive words were investigated in 22
      healthy subjects with high (HD) or low (LD) depressive scores. The ERP was
      recorded following a visual presentation of emotive adjectives. The adjectives
      presented included words that subjects felt to be fit or unfit to their own
      character or traits, and that they perceived as positive or negative. The latency
      of P300 (P1) for negative words was significantly longer than that for positive
      words at Pz in HD subjects. The N400 (N1) in HD subjects showed a longer latency
      than that in LD subjects (p<0.01) at Cz and Pz. However, there was no difference
      in amplitude between the fit and unfit category, nor in the positive or negative
      category of words between the LD and HD groups. The present study suggests that
      an excessive level of cognitive processing in response to passive stimulation by
      non-specific emotive words occurs in normal subjects with a depressive condition.

PMID- 16579174
TI  - Cognitive mechanism for meaning of emotive words in depressed personality: an
      event-related potential study.
AB  - We investigated the relationship between the ERP modulation of emotive words and
      the depression score in thirty-five healthy subjects with both high and low Beck
      Depression Inventory scores. The event-related evoked potentials (ERP) were
      measured following a visual presentation of emotive adjectives. Each word was
      classified into two sets of categories by each subject, i.e., positive or
      negative, and fit or unfit to his/her personality. The ERP signals were then
      separately averaged according to the subject's classifications. After
      stimulation, positive and negative ERP components at 200 ms (P2) and 400 ms (N2),
      respectively, were enhanced in amplitude in subjects with a high depression
      score. The enhancement of the P2 and N2 components was not related to the
      subject's categorization of the words. The results suggest that hypersensitivity
      to non-specific emotive words might be a neurophysiological phenomenon in a
      depressive state in healthy subjects.

PMID- 16579175
TI  - Simultaneous registration with ct-fluoro matching for spinal navigation surgery.
      A case report.
AB  - Computer-assisted surgery, which provides simultaneous, multiplanar images of
      bone structures, has become widely used. However, registration maneuvering
      remains time consuming. The objective of this paper is to document the usefulness
      of CT-fluoro matching for spinal navigation. A spinal navigation system
      (VECTORVISION compact; Brain LAB, Germany) and a digital imaging system (OEC9800;
      CATHEX, Tokyo, Japan) were used for CT-fluoro matching in cases of L4/5 and L5/S1
      posterior lumbar interbody fusion. A reference array was attached to the L4
      spinous process. Preoperative CT images and intraoperative fluoro-shots including
      L4, L5, and S1 were superimposed on the navigation monitor. Following insertion
      of L4 screws, a reference array remained to be attached to the L4 spinous
      process, after which a level definition and pre-registration of L5 and S1
      vertebrae were performed and the screwing procedure of L5 and S1 was completed
      without additional fluro-shots. Registration of three vertebrae was completed
      without paired-point or surface-matching procedures. The calculation time for the
      registration in a single vertebra was 30 sec. All pedicle screws were seen to be
      successfully inserted on postoperative CT images. We performed the navigation
      surgery by matching the preoperative CT images to the intraoperative fluoro-shots
      without manual registration. This technique may prove useful in the future for
      anterior spinal surgery and percutaneous screwing without the need for total
      exposure of the bone surface.

PMID- 16579176
TI  - Elective neck irradiation on ipsilateral side in patients with early tongue
      cancer for high-risk group with late cervical lymph node metastasis.
AB  - A prospective study was performed to assess the efficacy of elective neck
      irradiation (ENI) on the ipsilateral side in patients with early tongue cancer
      among a high-risk group with late cervical lymph node metastasis. Patients in the
      high-risk group had T2-tumors, excluding superficials or T1-tumors > or =19 mm in
      maximal diameter with invasion or ulcer. Between February 1989 and October 1997,
      70 patients with tongue cancer of Stages I and II were enrolled in the present
      study (ENI group: 31, non-ENI group: 39). In a combination therapy of external
      beam irradiation and brachytherapy, the standard dose of interstitial
      brachytherapy for primary tumors was approximately 60 Gy. Irradiation was
      initiated with a 9-MeV electron beam at a dose of 50 Gy on the ipsilateral side
      of the neck only when the day of brachytherapy approached. Three patients (9.7%)
      in the ENI group had neck lymph node metastasis as did 5 (12.8%) in the non-ENI
      group (p= 0.684). In patients with ulceration, the incidence of subsequent lymph
      node metastasis was significantly higher (p=0.029). Neck lymph node metastasis
      occurred in 2 (16.7%) of 12 patients with ulcers in the ENI group and in 2
      (66.7%) of 3 with ulcers in the non-ENI group. Although we could not demonstrate
      the significant efficacy of ENI in the high-risk group in this study, ENI
      decreased the neck lymph node metastasis. In addition, our results suggested that
      ENI particularly inhibits cervical lymph node metastasis in tongue tumor patients
      with ulcers.

PMID- 16579177
TI  - Gitelman's syndrome with silent thyroiditis.

PMID- 16579178
TI  - [Guides to medical writing and its publication].

PMID- 16579180
TI  - [Lymphocytes B and NK in respiratory allergy].
AB  - BACKGROUND: High affinity immunoglobulin E (IgE) receptors may activate the mast
      cell degradation; on the other hand, the ones of low affinity may activate B
      lymphocytes so they act as antigen-presenting cells and as producers of the same
      immunoglobulin. As allergic patients produce a great quantity of IgE they are
      prone to get an infection. OBJECTIVE: To quantify the IgE increase in 28 patients
      with allergic rhinitis or asthma, or both without having received a previous
      treatment. PATIENTS AND METHODS: 38 patients with allergic rhinitis, bronchial
      asthma, allergic conjunctivitis or atopic dermatitis diagnosis were included. B
      lymphocytes and NK cells immunophenotypification was made. Flow cytometry was
      used for cells lecture. Data were analyzed with descriptive statistics applying
      central tendency measurements. RESULTS: No variations were found in the values of
      any cell lineage. CONCLUSIONS: Proliferation and activation of B lymphocytes
      should be considered in allergic diseases as its quantification in serum may be a
      measurement parameter of allergic activity.

PMID- 16579179
TI  - [Correlation between chronic idiopathic urticaria and infection due to H.
      pylori].
AB  - BACKGROUND: H. pylori is considered one of the major etiological agents for
      chronic idiopathic urticaria; it infects 15 percent of the world's population and
      induces an inflammatory process in the gastric mucosa. In some cases it is
      related to chronic urticaria, even in the absence of digestive symptoms.
      OBJECTIVE: The purpose of this study is to find the correlation between chronic
      idiopathic urticaria and infection due to Helicobacter pylori. PATIENTS AND
      METHODS: Twenty patients with chronic idiopathic urticaria and a positive urea
      breath test for H. pylori were included in the study. All other frequent
      pathologies were eliminated. Patients began treatment with amoxicillin,
      clarithromycin and omeprazole for 14 days. Thirty days after the start of
      treatment, the urea breath test was performed in all of the patients. Also
      cutaneous symptoms were evaluated. RESULTS: Urticaria disappeared in 11 patients
      (55%), in 9 (45%) the urea breath test became negative and in two remained
      positive. Urticaria persisted in 9 patients (45%), in 6 (30%) the urea breath
      test was negative and in 3 (15%) persisted as positive. Only two patients (10%)
      experienced gastric symptoms. CONCLUSION: We found a correlation between the
      disappearance of the symptoms and a negative urea breath test in 45 percent of
      the patients who were studied. We must consider the possibility of H. pylori
      infection, which can be present even without gastric symptoms.

PMID- 16579181
TI  - [Comparison of two lancets in the skin prick test].
AB  - BACKGROUND: The skin prick test is used to diagnose the allergic sensitization.
      Its results depend upon several factors, such as the lancet type. In Cuba, the
      most frequently used are: ALK lancet and blood lancet. OBJECTIVE: To compare
      these two lancets regarding the size of the wheal, precision, sensitivity and
      specificity of the skin prick test and, finally, the preference of the patients
      to one of them. PATIENTS AND METHODS: The study was performed in 60 allergic
      patients, aged 15-50 years, seen at the allergy service of Hospital Universitario
      Clinico Quirurgico General Calixto Garcia. The skin prick test was performed on
      the forearm of all patients included, using both lancet types. A negative control
      (diluent solution) was applied, together with a 54.3 mmol/L histamine solution in
      five replicates. RESULTS: The mean size of skin reaction to histamine was 6 mm,
      using a 1 mm single peak lancet (ALK), size was 6.5 mm when using blood lancet
      (significant difference p < 0.05). Precision, sensitivity and specificity of ALK
      lancet were 9.7, 100 and 100%, respectively. On the other hand, the respective
      values for blood lancet were 15.9, 96 and 87%. Of those studied, 27% presented
      mild pain and 3% moderate pain using the ALK lancet; while 25% showed mild pain
      and 10% moderate pain using the blood lancet. CONCLUSION: The ALK lancet showed
      more precision, sensitivity and specificity and it was preferred by the patients.

PMID- 16579182
TI  - Clinical factors predicting a rapid response to short-acting beta2 agonists in
      mild and moderate asthma exacerbations.
AB  - BACKGROUND: The need for establishing criteria that facilitate decision-making
      has lead to search for factors that could predict prognosis and response to
      treatment for asthma exacerbations. OBJECTIVE: To assess which clinical factors
      are associated with a rapid response to short-acting beta2 agonists during asthma
      exacerbations. PATIENTS AND METHODS: Two hundred and twenty consecutive adults
      with mild to moderate asthma crisis were included. Their medical history and
      physical examinations were completed and closely monitored: heart rate,
      respiratory rate, SO2, and FEV-1. They were initially treated with O2 and
      micronebulized albuterol (2.5 mg every 20' x 4). A FEV-1 > or = 80% of predicted
      and an improvement at 90' were considered as good response. RESULTS: One hundred
      and forty-four (65.5%) patients had a good response to micronebulized albuterol,
      while 76 (34.5%) required steroids and hospitalization. Early relapse rate (72
      hours) in this study was low (3.4%) and it was associated to other factors, such
      as: upper airway infection (40%) and history of oral steroids usage in the
      previous year (80%). The variables associated to a good response were: < 6 hours
      since crisis started, no hospitalization or steroid use during a crisis in the
      last year, initial SO2 > or = 90% and initial FEV-1 > or = 60%. CONCLUSIONS:
      These variables are easily measured and predict a therapeutic response in asthma
      patients when first seen in the emergency room.

PMID- 16579183
TI  - [Chronic urticaria: clinical characteristics of a group of patients of Veracruz,
      Mexico].
AB  - BACKGROUND: Chronic urticaria and angioedema have a high incidence in the general
      population. Both diseases constitute a challenge in the identification of their
      causes, which in most of the cases are unknown. OBJECTIVE: To investigate some
      causes of chronic urticaria and angioedema, as well as its evolution in a group
      of patients. PATIENTS AND METHODS: 32 patients with chronic urticaria and
      angioedema, with poor response to the previous treatment, were included. A
      clinical history was made to all of them and they were asked for a complete
      hematic biometry, general urine exam, pharyngeal exudate, and coproparasitoscopic
      examinations. Some cases required other laboratory exams. RESULTS: There was a
      predominance of the female gender 22/32 (69%). It was observed that 75% of the
      patients had more than 20 years old. Evolution time has a mode between three and
      six months, with variations of three months to six years. We observed several
      types of intestinal parasites in 16 cases; each of them received specific
      treatment, but only five had an improvement of urticaria. Almost half of the
      patients presented wheals every day. We found seven cases with streptococcus beta
      hemolitic group A, from which three had improvement of urticaria with the
      antimicrobial treatment; there were four cases of leukorrhea/vulvovaginitis, with
      improvement after the treatment for candidiasis identified by laboratory.
      CONCLUSIONS: There was a predominance of adults with infectious and parasitic
      disease. It was identified in most of the cases and had good clinical response to
      the specific treatment.

PMID- 16579184
TI  - [Cow-milk's protein allergy].
AB  - Milk contains more than 40 proteins and all of them may act like human species
      antigens. The main allergens are beta lactoglobulin, casein, alpha lactoalbumin
      and seroalbumin; beta lactoglobulin is a protein not existing in human species
      and is found in maternal milk in minimal quantities (mcg) due to milky products
      ingested by the mother, these small quantities are responsible of the highest
      number of sensitizations to this protein. This article reviews the allergy to the
      cow-milk's protein, also, a critical route to its diagnosis and management is
      planted.

PMID- 16579185
TI  - World Health Organization classification of tumours: pathology and genetics of
      head and neck tumours.

PMID- 16579186
TI  - Partial medial canal fibrosis.

PMID- 16579187
TI  - Endoscopic view of an obstructing polyp of the uncinate fold.

PMID- 16579188
TI  - Pediatric foreign body and an unusual x-ray finding.

PMID- 16579189
TI  - Seborrheic keratosis.

PMID- 16579190
TI  - Ossifying fibroma of the ethmoid sinus.

PMID- 16579192
TI  - Parathyroid adenoma mimicking cervical recurrence on CT/PET fusion scan.

PMID- 16579193
TI  - High-resolution esophageal manometry.

PMID- 16579191
TI  - Meniere's syndrome, otosclerosis, and insulin resistance syndrome.

PMID- 16579194
TI  - Establish written policies on discounts, waivers, and other collection variables.

PMID- 16579195
TI  - Safety and efficacy of Sofenz ceruminolytic solution.
AB  - We conducted an open-label study of 109 untreated patients who had excessive or
      impacted cerumen. Our goal was to evaluate the safety and efficacy of Sofenz
      Cerumenolytic Solution, a methyltrypsin-containing earwax removal solution. Each
      patient's external auditory canal was filled with Sofenz for 15 minutes. The
      primary measure of efficacy--visibility of the tympanic membrane--was assessed
      after the solution had been drained from the canal and again after the canal had
      been irrigated with lukewarm water. If the tympanic membrane was not completely
      visible following either application, the procedure was repeated. A safety
      examination was conducted 1 to 3 days after treatment. Secondary outcomes
      measures included relief of otologic symptoms (e.g., hearing loss, tinnitus,
      etc.) and patients'overall satisfaction with treatment. Immediately after
      treatment, we found that the external auditory canal was completely visible in 81
      patients (74.3%) after 1 application of Sofenz and subsequent irrigation, and in
      98 patients (89.9%) after 2 applications of each. At the safety follow-up visit,
      we determined that the number of otologic symptoms had declined by 93.2%. A self
      reported assessment completed by each patient following the procedure revealed a
      high degree of satisfaction with treatment. A total of 58 adverse events were
      reported, but only 16 were directly related to treatment, and all were transient
      and either mild or moderate. We conclude that 1 or 2 applications of Sofenz
      followed by irrigation with lukewarm water is a safe, well-tolerated, and
      effective treatment for excessive or impacted cerumen in the external auditory
      canal.

PMID- 16579197
TI  - Sigmoid sinus thrombosis secondary to Lemierre's syndrome.
AB  - Lemierre's syndrome, a rare and almost forgotten cause of internal jugular vein
      thrombosis, is usually caused by an anaerobic head and neck infection. Left
      untreated, it can result in the release of septic emboli. We describe the case of
      a 42-year-old man who presented with fever and a tender, swollen neck mass.
      Computed tomography revealed an edematous parapharyngeal area and a compressed
      internal jugular vein. Despite antibiotic treatment, the patient's condition
      worsened, and a parapharyngeal fluid collection was drained 4 days later. Six
      weeks later, the patient returned to the outpatient department complaining of
      headaches, and he was found to have a tender, firm neck. He was readmitted, and
      magnetic resonance venography revealed a right internal jugular vein thrombosis
      that extended intracranially to the sigmoid sinus. He was anticoagulated for 6
      months, and he remained well during outpatient follow-up. We examine the
      controversial roles that anticoagulation and thrombolysis play in Lemierre's
      syndrome and sigmoid sinus thrombosis, and we review the diagnostic options.

PMID- 16579196
TI  - Combined therapy in the treatment of auricular keloids.
AB  - Management of earlobe keloids is still controversial. Many different treatment
      modalities have been employed; however, no single approach has been completely
      successful. We used combination therapy that included compression therapy, laser
      excision, and serial steroid injection, which has improved our therapeutic
      outcomes for earlobe keloids.

PMID- 16579198
TI  - Mandibular distraction osteogenesis with a small semiburied device in neonates:
      report of 2 cases.
AB  - Distraction osteogenesis has recently assumed an important role in the correction
      of craniofacial anomalies, particularly for the treatment of potentially life
      threatening, deformity-associated upper airway obstruction and respiratory
      dysfunction in neonates. Such deformities include Treacher Collins syndrome,
      Goldenhar 's syndrome, Nager's syndrome, temporomandibular joint ankylosis, and
      Pierre Robin sequence. These conditions frequently require a tracheostomy to
      maintain airway patency. We report our experience with using mandibular
      distraction as a valid alternative to tracheostomy. Minimally invasive surgery is
      possible with small semiburied devices.

PMID- 16579199
TI  - Kimura's disease of the parapharyngeal space.
AB  - Kimura's disease is a fairly uncommon inflammatory condition of unknown etiology.
      It classically presents in young Asian males as tumorlike subcutaneous nodules in
      the head and neck with associated lymphadenopathy, peripheral eosinophilia, and
      an elevated serum IgE level. Kimura's disease affects the subcutaneous tissues,
      salivary glands, and lymph nodes; less common sites in the head and neck include
      the eyelid and tympanic membrane. We report a case of Kimura's disease of the
      parapharyngeal space in a 42-year-old Chinese woman. To the best of our
      knowledge, this is the first report of Kimura's disease at this site.

PMID- 16579200
TI  - Primary laryngeal lymphoma: case report.
AB  - Extranodal laryngeal lymphoma is extremely rare. We report a case of primary
      laryngeal lymphoma in a 76-year-old man who had presented with a 7-week history
      of progressive hoarseness. Laryngoscopy revealed asymmetry of the right false
      vocal fold. Pathology of a deep biopsy specimen identified a malignant, diffuse,
      CD20-positive, B-cell lymphoma. The stage IE lymphoma completely resolved after
      treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
      and rituximab. Despite its relative rarity, the consequences of a missed
      diagnosis warrant vigilance for this type of laryngeal tumor.

PMID- 16579201
TI  - Unusual paratracheal masses presenting with vocal fold paralysis.
AB  - Most paratracheal masses are of thyroid origin. We describe two cases of vocal
      fold paralysis that were caused by unusual paratracheal masses. In one case, a 35
      year-old man was found to have a malignant lymphoma that originated in the
      mediastinum and extended above the clavicle. The other patient was a 53-year-old
      man with an enlarged left thyroid lobe, tumor invasion of the adjacent larynx and
      trachea, and multiple pulmonary nodules all due to adenoid cystic carcinoma.
      Unusual paratracheal masses presenting with vocal fold paralysis may mimic
      thyroid malignancies, thereby posing both diagnostic and therapeutic challenges.
      Fine-needle aspiration cytology is often helpful in making a definitive
      diagnosis, but incisional biopsy is necessary in some cases.

PMID- 16579202
TI  - A rare case of rhabdomyoma of the larynx causing airway obstruction.
AB  - Rhabdomyomas are benign tumors of skeletal muscle derivation. Rhabdomyomas of the
      head and neck are unusual, and laryngeal rhabdomyomas of the adult type are rare.
      When they do occur, patients may present with symptoms that have progressed
      slowly over several years. In extraordinary cases, stridor and airway obstruction
      manifest. We report a case of adult rhabdomyoma of the larynx that features some
      of its typical and atypical presenting characteristics. This case also
      exemplifies the favorable prognosis that results following complete yet
      conservative surgical excision.

PMID- 16579203
TI  - Congenital midline cervical cleft: a report of 3 cases.
AB  - Congenital midline cervical cleft is a rare anomaly of the anterior neck. The
      diagnosis is typically made on the basis of the lesion's characteristic clinical
      presentation at birth. It appears to occur as a result of a failure of fusion of
      the paired second branchial arches in the midline during embryogenesis. Surgical
      intervention is necessary to avoid potential long-term complications, such as
      contractures and limitation of neck mobility. We present 3 cases of congenital
      midline cervical cleft, and we discuss the embryology, presentation, and surgical
      management of this unusual condition.

PMID- 16579204
TI  - An assessment of risk factors for the development of a second primary malignancy
      in the head and neck.
AB  - This retrospective database study of 44,862 patients who had a history of a
      primary head and neck malignancy was conducted to identify any clinical variables
      that may predict the occurrence of a second primary head and neck malignancy.
      During a mean follow-up of 42.2 months, a second head and neck primary developed
      in 941 of these patients (2.1%). Statistical analyses revealed that a higher
      incidence of a second primary was associated with increased age and a location of
      the first primary in the larynx/hypopharynx, the oropharynx, a major salivary
      gland, or the nasopharynx. A lower incidence was associated with the presence of
      cervical nodal disease or treatment of the first primary with radiation therapy.
      Factors that had no effect on the risk of a second primary included sex, the size
      of the first primary tumor, a first-primary site in the oral cavity, and
      treatment of the first primary with cancer-directed surgery. The risk of a second
      primary head and neck cancer remained constant for at least 10 years.

PMID- 16579206
TI  - Gender-specific trends in the value of education and the emerging gender gap in
      college completion.
AB  - Analysis of March Current Population Survey data from 1964 through 2002 shows
      that white women overtook white men in their rates of college completion and that
      this phenomenon occurred during a period in which women's standard-of-living
      gains from college completion grew at a faster rate than those for men. We assess
      whether these trends are related to changes in the value of education for men and
      women in terms of earnings returns to higher education, the probability of
      getting and staying married, education-related differences in family standard of
      living, and insurance against living in poverty. Although returns to a college
      education in the form of earnings remained higher for women than for men over the
      entire period, trends in these returns do not provide a plausible explanation for
      gender-specific trends in college completion. But when broader measures of
      material well-being are taken into account, women's returns to higher education
      appear to have risen faster than those of men.

PMID- 16579205
TI  - Tuberculosis mimicking Kikuchi's disease.
AB  - Kikuchi's disease is an idiopathic self-limiting necrotizing lymphadenitis.
      Clinically, it mimics tuberculous cervical lymphadenopathy. The disease is
      diagnosed by histopathologic study. The only specific treatment that has been
      reported is empiric steroid therapy. We report a case of tuberculosis that was
      originally thought to be Kikuchi's disease in a 24-year-old man. When the
      patient's condition worsened during a course of steroid therapy, he underwent
      surgical exploration, which revealed the presence of tuberculous lymphadenitis.
      The patient was switched to antituberculosis drug therapy, and his improvement
      was dramatic.

PMID- 16579207
TI  - Family size and schooling in sub-Saharan African settings: a reexamination.
AB  - Contrary to theory and evidence from many other regions, previous studies in sub
      Saharan Africa have found surprisingly weak associations between family size and
      schooling. It is unclear; however, whether these weak results reflect (spurious)
      limitations in methodology or (real) differences in context. This study uses
      schooling histories from Cameroon to test four contending methodological and
      contextual explanations for these weak results: measurement bias, statistical
      estimation bias, family buffering, and socioeconomic context. We find the
      strongest support for the last explanation: the relationship between family size
      and schooling varies with spatial and historical context. This relationship has
      strengthened within the country over time, and this raises concern about the
      implications of current demographic transitions on inequality among children.

PMID- 16579208
TI  - Residential father family type and child well-being: investment versus selection.
AB  - This research links residence with biological and nonbiological married and
      unmarried parents to the cognitive achievement and behavioral problems of
      children aged 3-12, controlling for factors that make such families different.
      The data were drawn from the 1997 Child Development Supplement to the Panel Study
      of Income Dynamics. Achievement differences were not associated with father
      family structure per se, but with demographic and economic factors that differ
      across families. In contrast, behavioral problems were linked to family structure
      even after controls for measured and unmeasuredfactors were included. Children in
      all family types except the married-biological-parent family showed higher levels
      of behavioral problems. Paternal and maternal engagement time explained some of
      the differences in behavioral problems across families. Although children in
      blended families tended to achieve at lower levels than those not in
      blendedfamilies, stepchildren in blended families achieved at levels comparable
      to those of half-siblings. Finally, children in blended families tended to
      havefewer behavioral problems than those not in blended families.

PMID- 16579209
TI  - The demographics of same-sex marriages in Norway and Sweden.
AB  - The present study investigates the demographics of same-sex marriages--that is,
      registered partnerships-in Norway and Sweden. We give an overview of the
      demographic characteristics of the spouses of these partnerships, study patterns
      of their divorce risks, and compare the dynamics of same-sex couples with those
      of heterosexual marriages. We use longitudinal information from the population
      registers of the two countries that cover all persons in partnerships. Our
      demographic analyses include information on characteristics such as age, sex,
      geographic background, experience of previous opposite-sex marriage, parenthood,
      and educational attainment of the partners involved. The results show that in
      many respects, the distributions of married populations on these characteristics
      differ by the sex composition of the couples. Patterns in divorce risks are
      rather similar in same-sex and opposite-sex marriages, but divorce-risk levels
      are considerably higher in same-sex marriages. The divorce riskforfemale
      partnerships is double that for male partnerships.

PMID- 16579210
TI  - Do marriages forget their past? Marital stability in post-Khmer Rouge Cambodia.
AB  - This paper assesses the impact of three main destabilizing factors on marital
      stability in Cambodia: the radical reformation of marriage under the Khmers
      Rouges (KR); the imbalanced gender ratio among marriageable adults resulting from
      gendered mortality during the KR regime; and, after decades of isolation from the
      West, a period of rapid social change. Although there is evidence of declining
      marital stability in the most recent period, marriages contracted under the KR
      appear as stable as adjacent marriage cohorts. Thesefindings suggest that the
      conditions under which spouses were initially paired matter less for marital
      stability than does their contemporaneous environment.

PMID- 16579211
TI  - Why are cohabiting relationships more violent than marriages?.
AB  - In response to increases in cohabitation in the United States, researchers have
      recently focused on differences between cohabiting and marital unions. One
      consistent finding is a higher rate of domestic violence among cohabiting couples
      as compared with married couples. A prominent explanation for this finding is
      that cohabitation is governed by a different set of institutionalized controls
      than marriage. This article explores an alternative explanation, namely, that
      differences in selection out of cohabitation and marriage, including selection of
      the least-violent cohabiting couples into marriage and the most-violent married
      couples into divorce, lead to higher observed rates of violence among cohabiting
      couples in cross-sectional samples. Our results suggest that researchers should
      be cautious when making comparisons between married and cohabiting couples in
      which the dependent variable of interest is related to selection into and out of
      relationship status.

PMID- 16579212
TI  - Religious attendance and mortality: implications for the black-white mortality
      crossover.
AB  - This study investigates the relationships among religious attendance, mortality,
      and the black-white mortality crossover. We build on prior research by examining
      the link between attendance and mortality while testing whether religious
      involvement captures an important source of population heterogeneity that
      contributes to a crossover Using data from the Established Populations for
      Epidemiologic Studies of the Elderly, we find a strong negative association
      between attendance and mortality. Our results also show evidence of a racial
      crossover in mortality rates for both men and women. When religious attendance is
      modeled in terms of differential frailty, clear gender differences emerge. For
      women, the effect of attendance is race- and age-dependent, modifying the age at
      crossover by 10 years. For men, however; the effect of attendance is not related
      to race and does not alter the crossover pattern. When other health risks are
      modeled in terms of differential frailty, wefind neither race nor age-related
      effects. Overall, the results highlight the importance of considering religious
      attendance when examining racial and gender differences in age-specific mortality
      rates.

PMID- 16579215
TI  - Stomach upset? Don't blame milk.

PMID- 16579213
TI  - Measurement of cumulative physiological dysregulation in an older population.
AB  - The allostatic load framework postulates that an important pathway connecting the
      social environment with health involves biological responses to stressful stimuli
      and the subsequent dysregulation of interrelated physiological systems. We
      formulate a new measure for cumulative physiological dysregulation using a grade
      of membership model estimated with biodemographic data from a national sample of
      older Taiwanese persons. We investigate associations between the measure and
      physical, psychological, and cognitive function. The results provide insights
      into the relationships between a set of biological profiles and various health
      outcomes, identify limitations of earlier approaches, and underscore next steps
      in the development of improved for mulations of physiological dysregulation.

PMID- 16579214
TI  - Birth outcomes for Arabic-named women in California before and after September
      11.
AB  - Persons who were perceived to be Arabs experienced a period of increased
      harassment, violence, and workplace discrimination in the United States in the
      weeks immediately following September 11, 2001. Drawing on prior studies that
      have hypothesized that experiences of discrimination increase the risk of preterm
      birth and low birth weight, this study explores whether there was an effect on
      birth outcomes for pregnant women of Arab descent. California birth certificate
      data are used to determine the relative risk of poor birth outcomes by race,
      ethnicity, and nativity for women who gave birth in the six months following
      September 2001, compared with the same six calendar months one year earlier. The
      relative risk of poor birth outcomes was significantly elevated for Arabic-named
      women and not for any of the other groups.

PMID- 16579216
TI  - Caring for patients with heart failure.

PMID- 16579217
TI  - The job interview.

PMID- 16579218
TI  - "Everything depends on good nursing".
AB  - Nurses have always played a vital role in the response to outbreaks of deadly
      illnesses. The story of Alberta nurses' heroic efforts in the face of the Spanish
      influenza epidemic of 1918-19, in the absence of public health infrastructure,
      reminds us of the importance of preparedness. The virus, which accompanied
      soldiers returning from Europe after the First World War, spread quickly along
      transportation routes from Eastern Canada to the West. Although many nurses had
      not yet returned from war service, or were assisting in Halifax following the
      explosion of 1917, those who were available in Alberta vo unteered without
      hesitation to care for victims of the virus. In the absence of cure, good nursing
      care was usually the only treatment for the illness. Recognition of the need for
      planned response to crises, availability of resources and excellent skills and
      knowledge prompted nursing leaders to lobby the government for a formal public
      health system and contributed to the organization of professional nursing
      associations. In the likely event of another global influenza pandemic, nurses
      may draw upon the lessons of the past as they once again face the complex
      challenges of a modern health crisis.

PMID- 16579219
TI  - A welcome link for patients who are waiting.
AB  - In our present health-care system, wait-lists are unfortunately all too familiar.
      They create distress for both patients and health-care providers. Two nurses from
      the breast cancer site team of the Capital Health Queen Elizabeth II Cancer Care
      Program in Halifax, Nova Scotia, responded by developing a program that links
      breast cancer patients who have undergone surgery and are waiting for outpatient
      consultation with either a radiation or a medical oncology team. This "link" is
      by early intervention telephone contact with a nurse who cares for this patient
      population. Evaluation of the pilot program indicated high patient satisfaction.
      The authors outline the challenges in maintaining the program, even though it has
      had a positive impact on those awaiting health services.

PMID- 16579220
TI  - Brave heart.

PMID- 16579221
TI  - [Study on small intestinal submucosa as repair materials in urethral
      reconstruction].
AB  - OBJECTIVE: To explore the possibility of small intestinal submucosa (SIS) for
      reconstruction of urethral defect. METHODS: Twenty-four male rabbits were divided
      into 4 groups: group A (the tubular SIS graft for urethral repair), group B
      (control group, urethral tubular defect), group C (the SIS patch graft for
      urethral repairs), group D (control group, urethral part defect). Then the
      regenerative segment was studied with histological technique by hematoxylin-eosin
      straining and immunohistological straining for alpha-actin after 6 and 12 weeks
      postoperatively. The retrograde urethrography and urodynamics were used to
      evaluate the function of the regenerative urethra at 12 weeks after operation.
      RESULTS: In groups A and C, at 6 weeks after operation, the luminal surface of
      matrix was completely covered by urothelium, minimal SIS graft was observed in
      the extracellular matrix, new smooth-muscle cells was confirmed; however, more
      inflammatory cells were observed in the host-matrix anastomosis in group A than
      in group C. At 12 weeks postoperatively, the regenerative tissue was equivalent
      to the normal urethral tissue and SIS disappeared in group C, but some minimal
      SIS grafts were observed in group A. In groups B and D, urethral strictures and
      fibrous connective tissue were observed except 3 cases. The urethrography showed
      wide smooth urethral in group A and C, meanwhile urodynamic evaluation didn't
      demonstrate significant difference (P > 0.05) in the bladder volume and the
      maximum urethral pressure between preoperation and postoperation in group A or
      group C. CONCLUSION: SIS can be a useful material for urethral repair in rabbits,
      the SIS patch graft is superior to the tubular SIS graft in urethra
      reconstruction.

PMID- 16579222
TI  - [Biocompatibility of acellular urinary bladder submucosa].
AB  - OBJECTIVE: To investigate the biocompatibility of acellular urinary bladder
      submucosa (AUBS). METHODS: The acellular collagen matrix of human urinary bladder
      submucosa was developed using freeze-thawed enzymatic treatment and freeze-drying
      technique. Human oral keratinocytes were cultured and seeded on AUBS at a density
      of 2 x 10(6)/ml in vitro. The proliferation of the cells were observed. Pockets
      were created in the abdominal muscle wall of 18 SD rats. AUBS in size 1 cm x 1 cm
      was implanted into the pocket. The grafts were observed by light microscope 3, 6,
      10, 14, 21 and 28 days after operation. RESULTS: AUBS mainly consisted of
      collagen fibers with a three-dimensional network structure. After the oral
      keratinocytes were seeded, continuous oral epithelium layer was formed on the
      surface of AUBS after 10 days in vitro. Histological observation of the grafted
      AUBS showed progressive cell infiltration at 6 days. New capillaries formed at 14
      days. The collagen fibers arranged regularly at 28 days after implantation.
      CONCLUSION: Freeze-dried AUBS may be used as a suitable scaffold for tissue
      regeneration, which can induce cell proliferation both in vivo and in vitro and
      has good biocompatibility.

PMID- 16579223
TI  - [Reconstruction of urothelium tissue using issue-engineering technique].
AB  - OBJECTIVE: To evaluate the feasibility of reconstruction of urothelium tissue in
      vivo using tissue-engineering technique. METHODS: The urothelium cells were
      obtained from young rabbit, bladder by mechanical and enzyme digested methods.
      After expanded in vitro, the 4th to 5th generation urothelium cells were seeded
      onto the surface of 8 Polylatical/glycolic acid copolymer polymer, the polymer
      matrix without seeding cells served as control group. A total of 8 cell-polymer
      scaffolds and 4 simply scaffolds were separately implanted into subcutaneous
      pockets of athymic mice. The experiment groups included cell-polymer scaffolds 4
      weeks and cell-polymer scaffolds 8 weeks. The control group included simply
      scaffold 4 weeks and simply scaffold 8 weeks. After 4 and 8 weeks, the specimens
      were obtained and examined by gross inspection, histologically and
      immunohistochemically. RESULTS: The results of HE and Masson staining showed that
      the polymer were covered by urothelium cells layers and cells layers increased
      markley in experimental group. Immunocytochemical studies revealed that the cells
      were stained positively for anti-cytokeratins (AE1/AE3) in experimental group.
      Fiber tissue deposition were found on the surface of polymers in control group by
      HE and Masson staining. Immunocytochemical staining of implants showed the
      negative result for cytokeratins in control group. CONCLUSION: It is feasibility
      that reconstruction of urothelium tissue using tissue-engineering technique,which
      provides basic understandings for further development of the bladder and ureteral
      tissue engineered research.

PMID- 16579224
TI  - [Anatomical features of congenital chordee without hypospadias in children and
      implication for diagnosis and treatment].
AB  - OBJECTIVE: To investigate the anatomical features of congenital chordee without
      hypospadias in children and to discuss the diagnosis and treatment. METHODS: From
      August 1984 to December 2004, 94 children with chordee without hypospadias
      treated in the West China Hospital of Sichuan University were classified and
      analyzed for anatomical alterations. Their ages ranged from 18 months to 13 years
      (mean 6. 9 years). Ninety-four patients were divided into four groups. With
      intraoperation artificial erection, the patients with penis straightened after
      degloving were classified as type I patients (skin-tethering), those with penis
      straightened after fibrotic tissue in Buck's fascia released as type II patients
      (dysgenetic fascia), those with normal urethra and orthoplasty failed after
      degloving and removing fibrotic tissue as type III patients (corporal
      disproportion), and those with dysgenetic urethra tethering the corpora cavernosa
      as type lV patients (short urethra). RESULTS: In type I (n = 31, 32.9%) patients,
      the ventral skin and dartos fascia were contracted while Buck's fascia and the
      urethra was normal, in some (7 cases) scrotal skin extended to the ventral
      portion of penis (webbed penis). In type II (n = 45, 47.9%), contracture of
      Buck's fascia was evident and the thickening fibrotic tissue constituted the
      chief obstacle to orthoplasty, though in some skin was shortened. In type III (n
      = 6), the dorsal and ventral sides of the corpora cavernosa were
      disproportionated, and the morphologically normal urethra tightly adhered to the
      ventral aspect of corpora cavernosa. In some cases ventral skin and fascia were
      contracted, but orthoplasty could not be achieved through releasing these layers.
      In type IV (n = 12, 12.8%), the distal urethra was paper-thin and lacking corpus
      spongiosum, or dense fibrotic bands were found to be deep to the urethra. The
      urethra tethered the corpora cavernosa and formed a bow-to-string relation. The
      overlying skin and fascia were contracted in varying degrees while none had
      significance in straightening the penis. After operation, the length of penis
      increased to 6.9 cm from 5.2 cm on average and the chordee was corrected to 1.6
      degrees from 42.6 degrees before operation on average. The patients were followed
      up 1 months to 15 years. The results were satisfactory. Chordee remained in 2
      cases, fistula and urethral stricture occurred in 2 cases respectively, fistula
      in association with urethral stricture and diverticulum in 1 case; the operation
      was given again and the results was satisfactory. CONCLUSION: Patients with
      chordee without hypospadias may be divided into four types depending on which
      layer of the ventral penis constitutes the chief contribution to chordee. A
      systematic approach with repeated artificial erection tests is needed in
      determining the classification and surgical correction.

PMID- 16579225
TI  - [One stage repair of hypospadias using meatal-based flap overlapping with buccal
      mucosal graft].
AB  - OBJECTIVE: To explore the feasibility of one-stage repair of hypospadias using
      the meatal-based flap overlapping with buccal mucosal graft. METHODS: From March
      2002 to May 2004, 21 patients with hypospadias were treated with the meatal-based
      flap overlapping with buccal mucosal graft. Their ages ranged from 14 months to 8
      years. The procedure were as follows: urethral plate at proximal corona was cut
      to correct glandular tilt and chordee; the buccal mucosa taking from inner cheek
      was then fixed on tunica albuginea of ventral shaft with suture; and the meatal
      based flap was rotated distally and overlaid with buccal mucosal graft to repair
      urethra. RESULTS: All patients were followed up 3-18 months (7 months on
      average). A cosmetic glans and a vertically oriented, normal appearing slit
      meatus were achieved. Two patients had fistulas on lateral corona. Fistula
      spontaneously healed in 1 case and the other one was repaired after 6 months.
      CONCLUSION: The technique of meatal-based flap overlapping with buccal mucosal
      graft can completely correct glandular tilt and chordee, prove good cosmetic and
      functional glans and meatus.

PMID- 16579226
TI  - [Effect of niti-alloy urethral stent in hypospadias repair].
AB  - OBJECTIVE: To evaluate the effect of niti-alloy urethral stent on the prevention
      of urethrocutaneous fistula and urethral stricture in hypospadias repair.
      METHODS: From January 2001 to December 2004, niti-alloy urethral stents were
      applied to repair congenital hypospadias in 63 patients. Among 63 patients, 49
      (19 cases of proximal hypospadias, 22 cases of penoscrotal hypospadias and 8
      cases of perineoscrotal hypospadias) received one-stage surgical managements of
      urethral reconstruction, and 10 underwent postoperative fistular repairs and 4
      received repeated urethral reconstruction because of urethral stricture after
      hypospadias repair. RESULTS: All patients gained healing by first intention
      without fistula or urethral stricture. The stents were left indwelling in the
      neourethra for 2 months to 3 months to prevent stricture. The longest indwelling
      period was about 1 year. No dysuria or other discomfort occurred during this
      period. CONCLUSION: Niti-alloy urethral stent can effectively prevent the
      postoperative urethrocutaneous fistula and urethral stricture after hypospadias
      repair.

PMID- 16579227
TI  - [Tubularized incised plate urethroplasty for hypospadias in children].
AB  - OBJECTIVE: To present the experience of hypospadias repair using the tubularized
      incised plate urethroplasty (Snodgrass procedure). METHODS: From May 2001 to
      November 2004, 82 patients with hypospadias underwent the Snodgrass procedure and
      the clinical data were analysed retrospectively. The mean age was 5 years (1.5 to
      16 years). These cases were divided into: the earlier stage group (34 cases) and
      the later stage group (48 cases); the proximal group (19 cases) and the distal
      and middle group (63 cases); the primary operational group (49 cases) and the
      preoperational group (33 cases). RESULTS: Fistulas occurred in 12 patients
      (14.6%), complete glans dehiscence in 1 case. Fistula were as follows: 11 cases
      in the earlier stage group (32.4%) and 1 case in the later stage group (2.1%); 2
      cases in the proximal group (10.5%) and 10 cases in the group of distal and
      middle group (15.9%); 8 cases in the primary operational group (16.1%) and 4
      cases in the preoperational group (12.1%). There was statistically significant
      difference in the incidence of fistula between the earlier stage group and the
      later stage group (P < 0.01). There was no statistically significant difference
      between the proximal group and the distal and middle group, between the primary
      operational group and the preoperational group (P > 0.05). All patients were
      followed up more than one month. The neo-meatus was in normal position. The
      results of penile cosmetic and urethral function were satisfactory. Of these
      cases, 15 were followed up 1.5-6.0 months. The average flow rate was 7.8 ml/s
      (6.8-10.5 ml/s). The mean of maximum flow rate was 10. 5 ml/s (8.8-14.5 ml/s).
      CONCLUSION: Excellent neourethral functional and superior cosmetic results with
      low rate of complication can be gained by using tubularized incised plate
      urethroplasty for the cases of hypospadias without chordee or with mild chordee.
      But the preputial flap procedure should be chosen in condition that the
      hypospadias was association with obvious chordee.

PMID- 16579228
TI  - [Reconstruction of urethra partial defect with scrotal flap].
AB  - OBJECTIVE: To introduce the application of the scrotal flap on reconstructing
      partial urethra defect. METHODS: From March 1998 to August 2004, 31 patients with
      urethra defect were treated with scrotal flap. Their ages ranged from 6 to 34
      years. Thirty-one patients included 8 cases of congenital deformity of urethra
      and 23 cases of complication of urethral fistula, urethral stenosis and phallus
      bend after hypospadias repair. The flap widths were 1.5-2.5 cm in child and 2.5
      3.5 cm in adult. The flap length was 1.5-2.0 times as much as the width. Nine
      cases were classified as penile type, 10 cases as penoscrotal type, 7 cases as
      scrotal type (3 children in association with cleft scrotum) and 5 cases as
      perineal type because of pseudohermaphroditism. Urethroplasty was given by
      scrotal fascia vascular net flap to reconstruct urethra defect. RESULTS: All the
      flaps survived, and the incision healed well. Twenty-four cases achieved healing
      by first intention and 7 cases by second intention. And fistula occurred and
      healed after 2 weeks in 1 case. 27 cases were followed up 1-4 years, 2 cases had
      slight chordee, the others were satisfactivly. CONCLUSION: Urethroplasty with
      scrotal fascia vascular net flap is an ideal method for the partial defect
      urethra.

PMID- 16579229
TI  - [Treatment of female stress urinary incontinence with tension-free vaginal tape].
AB  - OBJECTIVE: To investigate the indication, approaches and prevention of
      complications in treatment of female stress urinary incontinence (SUI) with
      tension-free vaginal tape (TVT). METHODS: From September 2003 to December 2004,
      40 cases of female stress urinary incontinence were treated, including 8 cases in
      association with cystocele or rectocele and 1 case in association with uterine
      prolapse. They ranged from 30 to 70 years in age with an average of 56.3 years.
      The disease course was 1-42 years (7.2 years on average). All patients received
      TVT. In the patients suffering from uterine prolapse and cystocele or rectocele,
      butterfly-shaped mesh patch was applied. RESULTS: All patients achieved
      satisfactory results. The complications included slight dysuria (2 cases),
      vesical perforation (1 case) and pelvic hematoma (1 case) and cleared up after
      treating. All cases were followed up 1 to 15 months and the results were
      satisfactory. No urinary incontinence and no dysuria reoccurred. CONCLUSION: TVT
      is effective for SUI.

PMID- 16579230
TI  - [Rebuilding of scrotum in gangrene].
AB  - OBJECTIVE: To study diagnosis, treatment and rebuilding of scrotum gangrene.
      METHODS: From January 1992 to September 2004, 15 patients with scrotum gangrene
      were treated and their clinical data were analysed. Their ages ranged from 23 to
      80 years. The results of bacterial culture were positive for wound sample in 14
      cases and for blood in 1 case. All the patients underwent surgical treatment
      including incision, aggressive debridement, drainage, irrigation and antibiotic
      therapy. Two patients accepted hyperbaric oxygen therapy. All the patients
      received scrotum rebuilding by transfer of skin flap, skin grafting and
      saturation and orchiectomy was given in 2 elder patients. RESULTS: All the
      patients received healing by first intention after 21 to 34 days. There was no
      death. After a follow-up of 1 to 3 years, the appearance of scrotum was
      satisfactory and no orchiatrophy occurred. Thirteen patients with testicles had
      normal sexual function. CONCLUSION: After a definite diagnosis, early aggressive
      debridement, broad-spectrum antibiotics and sufficient local drainage should be
      used. If available, hyperbaric oxygen therapy may be used to promote healing of
      tissue wound. Scrotum should be rebuilt based on different conditions.

PMID- 16579231
TI  - [Balloon dilatation for lower urethral obstruction in children].
AB  - OBJECTIVE: To evaluate the clinical effect of balloon dilatation in the treatment
      of lower urinary tract obstruction in children. METHODS: Twenty-six boys
      suffering from lower urinary tract obstruction underwent the balloon dilatation
      operation. These patients included 23 cases of posterior urethral valves, 2 cases
      of anterior urethral valves and 1 case of traumatic urinary tract stricture.
      Their ages ranged from 18 days to 7 years. All the patients were diagnosed by
      voiding cystourethrogram (VCG). Some of the boys suffered from bilateral
      hydronephrosis and dilated ureters. Before operation, the patients with urine
      retention or abnormal renal function should drain urine and correct the disorder
      of fluid and electrolyte. Balloon dilatation was done after their conditions were
      improved. During operation, ketamine anaesthesia was used, and 30% diatrizoate
      meglumine was used as dilatation drug. The balloon catheters which had the length
      of 4 cm and the diameters of 5, 8,10 mm respectively were used for dilating the
      urethra. After operation, a Foley's catheter was routinely indwelled. RESULTS:
      During procedure, compression phenomena disappeared in the course of operation.
      All the patients urinated normally after catheter was removed at 1 week post
      operatively. 6 cases received ureteral reimplantation to prevent vesicoureteral
      reflux after 1 to 3 months. 25 patients were followed up from 1 to 13 years and
      all patients had normal micturition and the bilateral hydronephrosis were
      improved. CONCLUSION: Balloon dilatation is a safe, effective and feasible
      therapy for lower urinary tract obstruction in children.

PMID- 16579232
TI  - [Diagnosis and treatment of concealed penis in 43 children].
AB  - OBJECTIVE: To improve the diagnosis and treatment of concealed penis in children.
      METHODS: From August 1998 to January 2004, 43 cases of concealed penis in
      children were treated with Huang Lugang's procedure aging aged 2-14 years (7
      years on average). Eight children are obesity. The albuginea tissue were fixed to
      the lateral Buck's fascia at the base of the penis. Removal of the excessive
      suprapubic fat was given in 2 cases of obesity type. RESULTS: All patients were
      followed up from 3 to 24 months. The results were satisfactory in 35 (81.4%). The
      penile contour were dissatisfactory in 8 patients with obesity including 2
      patients given removal of the excessive suprapubic fat. CONCLUSION: The Huang
      Lugang's procedure was simple and can achieved satisfactory results, but it
      should be used carefully in case of obesity type.

PMID- 16579233
TI  - [Advance in urethral reconstruction with tissue engineering techniques].
AB  - OBJECTIVE: To sum up the research advances in urethra reconstruction with tissue
      engineering techniques. METHODS: The recent original articles about urethra
      reconstruction with engineering techniques were extensively reviewed. RESULTS: At
      present, human urothelium and smooth muscle cells have been successfully
      harvested, cultivated, and expanded in vitro in sufficient quantities for
      reconstruction. Tissue engineering for urethral reconstruction includes matrices
      alone, the body's natural ability which induces new tissue growth, or the use of
      matrices with cells. CONCLUSION: The tissue engineering materials for urethral
      reconstruction has been used successfully to repair defect of hypospadias and
      urethral strictures. The reconstruction of complex urethral defects need to be
      improved and developed.

PMID- 16579235
TI  - [Experimental studies on decorin in suppression of postoperative flexor tendon
      adhesion in rabbits].
AB  - OBJECTIVE: To study the effect of decorin in the suppression of postoperative
      flexor tendon adhesion. METHODS: Eighteen Japanese large ear white rabbits
      underwent complete transection of the II digit flexor digitorum profundus tendon
      in zone I and defects immediately were repaired using the modified Kessler
      technique with 5-0 nonabsorbable monofilament suture. The site of the right
      repaired tendon was then injected with 100 microl of decorin (0.25 mg/ml) as test
      toe, the site of the left repaired tendon with 100 microl of PBS as control toe.
      In every group, rabbits were killed and the feet were prepared for biomechanical
      testing, macroscopic examination and histological inspection. RESULTS: In every
      group, biomechanical testing demonstrates that the sliding distances and the
      ranges of motion significantly increased in the test toe compared with the
      control toe (P < 0.05); macroscopic examination demonstrated that the tendon
      adhesions of the test toe were significantly reduced when compared with the
      control toe. In the tese toe, hematoxylin and eosin staining revealed that the
      hyperplasia of fibroblast was significantly delayed and the collagen fibrils
      arranged regularly and had the normal diameters. CONCLUSION: Decorin can
      significantly reduce the flexor tendon adhesion formation, adjust collagen
      fibrillogenesis and promote the tendon healing.

PMID- 16579236
TI  - [Clinical application of the distally based sural island flap and
      myofasciocutaneous flap].
AB  - OBJECTIVE: To investigate the clinical efficiency of the distally based sural
      island flap and myofasciocutaneous flap in reconstruction of defect and
      osteomyelitic cavity of the ankle and foot. METHODS: From June 1997 to October
      2004, 21 patients with soft tissue defects and osteomyelitis in the ankle and
      foot were treated with the distally based sural island flap and
      myofasciocutaneous flap. There were 20 males and 1 female aging from 6 to 78
      years. The defect was caused by soft tissue defect trauma (18 cases) and
      electrical injury (3 cases). Among 21 patients, 17 were treated with island
      flaps, 4 by the myofasciocutaneous flap. The size of flaps ranged from 4 cm x 5
      cm to 16 cm x 22 cm. The donor sites were closed directly in 4 cases. RESULTS:
      The flaps completely survived in 21 cases and healing by first intention was
      achieved. After a follow-up of 3-6 months, no complication occurred. The color
      and texture of the flaps were good. The appearance and the function were
      satisfactory. CONCLUSION: Distally based sural flap is a reliable flap. This flap
      has rich blood supply without sacrifice of major arteries. Flap elevation is
      easy. It is very useful in repairing large soft tissue defects of the lower leg,
      the ankle and the foot, especially in repairing deep soft tissue defects and
      osteomyelitic cavities.

PMID- 16579234
TI  - [Effects of ectomesenchymal stem cells on hematopoiesis after total body
      irradiation].
AB  - OBJECTIVE: To investigate the effects of ectomesenchymal stem cells on
      hematopoiesis after total body irradiation in rats. METHODS: The primary
      ectomesenchymal stem cells were isolated from E11.5 SD fetal mandibular processes
      by 2.5 g/L trypsin and cultured with DMEM/F12. The morphology and growth rate
      were observed by inverted microscope. Eighty SD male rats randomly divided into
      ectomesenchymal stem cells group (n = 20), fibroblast group (n = 20), saline
      group (n = 20) and control group (n = 20), the first three groups were irradiated
      with 60Co gamma rays at 6. 0 Gy. The number of their bone marrow nucleated cells
      was counted after 4 weeks; the forming ability of colony-forming unit-granulocyte
      macrophage (CFU-GM) and histopathology of bone marrow were also observed.
      RESULTS: The cultured cells displayed monolayer growth and fibroblast-like with 2
      4 processes. The ectomesenchymal stem cells could increase the number of bone
      marrow nucleated cells and peripheral blood white cell count, and improve the
      forming ability of CFU-GM. After 4 weeks of transplantation, the number of the
      peripheral blood white cells in group A was more than that in groups B and C (P <
      0.05), the contents of Hb in groups A and D was significantly higher than those
      in groups B and C (P < 0.05). After 4 weeks, the bone marrow nucleated cells in
      group A were significant more than those in groups B and C (P < 0.01); CFU-GM in
      groups A and D was higher than that in groups B and C (P < 0.01). CONCLUSION:
      Ectomesenchymal stem cells have characteristics of stem cells. It may improve
      hematopoiesis recovery of irradiated rats.

PMID- 16579237
TI  - [Applied anatomy study and clinical application of great saphenous veno-saphenous
      neurocutaneous vascular flap].
AB  - OBJECTIVE: To provide the anatomic basis for defect repair of the knee, leg, foot
      and ankle with great saphenous veno-saphenous neurocutaneous vascular island
      flaps. METHODS: The origin, diameter, branches, distribution and anastomoses of
      the saphenous artery and saphenous neurocutaneous vascular were observed on 20
      sides of adult leg specimens and 4 fresh cadaver voluntary legs. Another 4 fresh
      cadaver voluntary legs were radiographed with a soft X-ray system after the
      intravenous injection of Vermilion and cross-sections under profound fascial,
      other hand, micro-anatomic examination was also performed in these 4 fresh
      cadaver legs. The soft tissue defects in lower extremity, upper extremity, heel
      or Hucou in hand were repaired with the proximal or distal pedicle flaps or free
      flaps in 18 patients (12 males and 6 females,aging from 7 to 53 years). The
      defect was caused by trauma, tumour, ulcer and scar. The locations were Hucou (1
      case), upper leg (3 cases), lower extremity and heal (14 cases). Of then, 7 cases
      were complicated by bone exposure, 3 cases by tendon exposure and 1 case by steel
      espouse, the defect size were 4 cm x 4 cm to 7 cm x 13 cm. The flap sizes were 4
      cm x 6 cm to 8 cm x 15 cm, which pedicle length was 8-11 cm with 2.5-4.0 cm
      fascia and 1-2 cm skin at width. RESULTS: Genus descending genicular artery began
      from 9.33 +/- 0.81 cm away from upper the condyles medialis, it branched
      saphenous artery accompanying saphenous nerve descendent. And saphenous artery
      reached the surface of the skin 7.21 +/- 0.82 cm away from lower the condyles
      medialis, and anastomosed with the branches of tibialis posterior artery, like
      "Y" or "T" pattern. The chain linking system of arteries were found accompanying
      along the great saphenous vein as saphenous nerve, and then a axis blood vessel
      was formed. The small artery of only 0.05-0.10 mm in diameter, distributed around
      the great saphenous vein within 5-8 mm and arranged parallelly along the vein
      like water wave in soft X-ray film. All proximal flaps, distal pedicle flaps and
      free flaps survived well. The appearance, sensation and function were
      satisfactory in 14 patients after a follow-up of 6-12 months. CONCLUSION: The
      great saphenous vein as well as saphenous neurocutaneous has a chain linking
      system vascular net. A flap with the vascular net can be transplanted by free, by
      reversed pedicle, or by direct pedicle to repair the wound of upper leg and foot.
      A superficial vein-superficial neurocutaneous vascular flap with abundance blood
      supply and without sacrificing a main artery is a favourite method in repair of
      soft tissue defects in foot and lower extremity.

PMID- 16579238
TI  - Ectopia of epidermal stem cells on wound edge during wound healing process.
AB  - OBJECTIVE: To investigated the distribution of epidermal stem cells in rat full
      thickness wound tissues during the wound healing process and to elucidate the
      roles of epidermal stem cells in wound repair in vivo. METHODS: Eighty circular
      full-thickness wounds were produced on both sides of the back in 20 male Wistar
      rats labeled with BrdU 60 days previously (4 wounds in each rat). BrdU, beta1
      integrin and keratin 19 (K19) were employed to determine the epidermal stem cells
      with SP immunohistochemical methods, and the epithelialization was determined
      with routine histological methods of HE staining on the 3rd, 7th, 14th, and 21st
      days after operation. RESULTS: No cells with positive immunostaining for beta1
      integrin, K19 and BrdU were found in granulation tissue of wound in both groups
      during the healing process. However, a few scattered beta1 integrin and K19
      positive cells were found within the stratum spinosum and stratum granulosum of
      the epidermis on the wound edges on the 3rd day post-injury. And these positive
      cells gradually became more and more in number, and mostly concentrated on the
      border of wound edges till the wounds healed. In addition, the number of positive
      cells for beta1 integrin and K19 in the infected wounds was less than that in non
      infected wounds. These positive cells for beta1 integrin and K19 staining on the
      wound edge were also positively stained with BrdU in the cellular nuclei.
      CONCLUSION: The above results indicate that ectopia of epidermal stem cells
      present a major function during wound epithelialization.

PMID- 16579239
TI  - [Treatment of intra-articular fracture with absorbable screws and rods].
AB  - OBJECTIVE: To assess the treatment effect of intra-articular fracture with
      absorbable screws and rods. METHODS: From June 1998 to August 2004, 35 patients
      with intra-articular fracture were treated by absorbable screws and rods made of
      self-reinforced polyglycolic acid (SR-PGA) and self-reinforced poly-L-Lactic acid
      (SR-PLLA). Of 35 patients, 30 were males and 5 were females (aged from 4 to 62
      years). All cases had intra-articular or periarticular fracture. The interval
      between injury and operation was 3 hours to 29 days. Fracture were fixed with
      full thread screws of SR-PGA in 9 cases, with tensile screws of SR-PLLA in 26
      cases, with rods of SR-PLLA in 15 cases. Bone traction or plaster external
      fixation were carried out postoperatively. RESULTS: The patients were followed
      from 3 months to 60 months with an average of 28 months. The wounds healed by
      first intention, and the healing time of bone was 1-3 months. No dislocation,
      infection and local effusion occurred. Functional recovery was satisfactory.
      According to AASO articular function standard, the results were excellent in 26
      cases, good in 7 cases, fair in 1 case, and poor in 1 case; the total excellent
      and good rate was 94.3%. CONCLUSION: Internal fixation of absorbable screws and
      rods are a perfect procedure in treating intra-articular and periarticular
      fracture, which can avoid the pain of taking out internal fixation materials
      because of second operation.

PMID- 16579240
TI  - [Treatment of fractures of proximal radius with Ni-Ti shape memory alloy
      embracing].
AB  - OBJECTIVE: To find out an ideal method of internal fixation for the treatment of
      fractures of proximal radius. METHODS: From August 2001 to April 2004, 24
      patients suffering from fractures of proximal radius were treated with Ni-Ti
      shape memory alloy embracing fixator. Of 24 patients, there were 19 males and 5
      females, aging from 16 to 48 years; there were 9 cases of wrestling injury, 5
      cases of crush injury, 4 cases of traffic accident injury, 3 cases of direct
      violence impact injury and 3 cases of high falling injury. All patients were
      given operation according to fix method of the shape memory alloy embracing
      fixator. All cases were regularly followed up to observe the fracture healing and
      functional recovery. RESULTS: All cases were followed up postoperatively from 4
      months to 21 months with an average of 10 months. No complication occurred during
      operation and after operation. Healing by first intention was achieved. X-ray
      showed that all cases achieved clinical union 8-12 weeks after operation.
      According to Anderson's criteria and the results were excellent in 18 cases, good
      in 5 cases, and fair in 1 case. The excellent and good rate was 95.83%.
      CONCLUSION: The internal fixation with shape memory alloy embracing fixator has
      as follows advantages: less trauma, esay-to-do, stable fixation, better tissue
      compatibility and less complication in treating fractures of proximal radius.
      This method can enhance the fracture healing and functional recovery. So it is a
      better method to treat fractures of proximal radius.

PMID- 16579241
TI  - [Basic concept in computer assisted surgery].
AB  - OBJECTIVE: To investigate application of medical digital imaging systems and
      computer technologies in orthopedics. METHODS: The main computer-assisted surgery
      systems comprise the four following subcategories. RESULTS: (1) A collection and
      recording process for digital data on each patient, including preoperative images
      (CT scans, MRI, standard X-rays), intraoperative visualization (fluoroscopy,
      ultrasound), and intraoperative position and orientation of surgical instruments
      or bone sections (using 3D localises). Data merging based on the matching of
      preoperative imaging (CT scans, MRI, standard X-rays) and intraoperative
      visualization (anatomical landmarks, or bone surfaces digitized intraoperatively
      via 3D localiser; intraoperative ultrasound images processed for delineation of
      bone contours). (2) In cases where only intraoperative images are used for
      computer-assisted surgical navigation, the calibration of the intraoperative
      imaging system replaces the merged data system, which is then no longer
      necessary. (3) A system that provides aid in decision-making, so that the
      surgical approach is planned on basis of multimodal information: the interactive
      positioning of surgical instruments or bone sections transmitted via pre- or
      intraoperative images, display of elements to guide surgical navigation
      (direction, axis, orientation, length and diameter of a surgical instrument,
      impingement, etc. ). And (4) A system that monitors the surgical procedure,
      thereby ensuring that the optimal strategy defined at the preoperative stage is
      taken into account. CONCLUSION: It is possible that computer-assisted orthopedic
      surgery systems will enable surgeons to better assess the accuracy and
      reliability of the various operative techniques, an indispensable stage in the
      optimization of surgery.

PMID- 16579242
TI  - [Diagnosis and treatment of deltoid contracture in children].
AB  - OBJECTIVE: To reinforce the recognization of deltoid contracture in children and
      probe its causes, pathomechanism, diagnosis and treatments. METHODS: The Clinical
      data were summarized and analysed, including etiological factors, clinical
      situations, examinations and treatments from 9 child patients with deltoid
      contracture from 1992 to 2004. The 9 child patients were followed up to evaluate
      therapeutic efficacy. RESULTS: Nine child patients with deltoid contracture
      included 4 boys and 5 girls, who aged from 5 to 14 years. The main clinical
      features were presented as abductive deformity, limitation of adduction of the
      shoulder, winging of the scapula, and dimpling of the skin with a palpable
      fibrous hard band in deltoid muscle. Four cases had a history of intramuscular
      injections in deltoid and 1 case was accompanied with bilateral gluteul
      contracture. Among the 9 patients, 8 cases were misdiagnosed before correct
      diagnosis and treatment. The misdiagnosis rate was up to 90%. All the cases
      received the operative treatments to release fibrous bands and were followed up
      for 8 months to 12 years. Abductive deformity disappeared and functions of the
      shoulders recovered in all patients, except 1 patient who had a lightly winged
      scapula. CONCLUSION: Deltoid contracture may be caused by multiple factors, but
      its clinical features are conductive to correct diagnosis and excellent
      therapeutic efficacy can be acquired by operation early.

PMID- 16579243
TI  - [Experimental study on porcine keratinocytes cultured and purified rapidly and
      cocultured on acellular amnion in vitro].
AB  - OBJECTIVE: To explore an effective method to culture and purify porcine
      keratinocytes, to observe the morphological characteristics of porcine
      keratinocytes growing on acellular amnion and to offer the experimental basis for
      that the amnion is used for tissue engineering. METHODS: The primary porcine
      keratinocytes were cultivated with DKSFM (Defined keratinocyte-SFM) containing
      10% fetal bovine serum (FBS). The second passage porcine keratinocytes were
      cultivated with the medium of DKSFM containing different concentrations of FBS.
      Because of the speciality that keratinocytes stick to flask fast, we purified the
      keratinocytes by 0.02% EDTA and 0.05% trypsin step by step. The second passage
      keratinocytes were seeded on amnion, the keratinocytes/amnion composites were
      observed by dye directly, histopathology and immunohistochemical staining.
      RESULTS: The proliferation of the primary porcine keratinocytes cultured with the
      medium of DKSFM containing 10% FBS was fast and the morphological characteristics
      were good. The cultivated porcine keratinocytes expanded to 60%-70% of the total
      area of the bottle of the flask after 5 days. The proliferation of the second
      passage porcine keratinocytes cultivated with the medium that DKSFM containing 5%
      FBS was faster than the second porcine keratinocytes cultured with the medium of
      DKSFM containing 10% FBS, or DKSFM without FBS. The proliferation of the second
      passage porcine keratinocytes cultivated with DKSFM without FBS was the slowest
      one among the 3 medium. The porcine keratinocytes that were purified by 0.02%
      EDTA and 0.05% trypsin step by step were got with high pure. After the
      keratinocytes were cultivated on the surface of amnion 12 days, the keratinocytes
      form a single layer on the surface of amnion and the cells were polygon and
      arranged like slab- stone. After 14 and 16 days, the cells contacted more
      closely. But at 16 days after the cells were seeded, some of the cells got aging.
      CONCLUSION: To culture primary porcine keratinocytes with the medium that DKSFM
      containing 10% FBS and to cultivate the second passage with the medium containing
      5% FBS, the proliferation of porcine keratinocytes are faster. The method that
      purify the porcine keratinocytes is effective. Acellular amnion offers excellent
      bioscaffold to support keratinocytes to adhere and grow. After the porcine
      keratinocytes are cultivated on the surface of the acellular amnion 12 days, the
      morphologic characteristics are better than that of other groups.

PMID- 16579244
TI  - [Experimental study on acellular bovine pericardium guided bone regeneration
      material].
AB  - OBJECTIVE: To choose the best procedure on preparation of acellular bovine
      pericardium (ABP) guided bone regeneration (GBR) material. METHODS: The BP was
      decellularized with 0. 25% Trypsin + 0.5% Triton X-100. The acellular bovine
      pericardiums (ABPs) were treated with phosphate-buffered saline(PBS) (group A),
      95% glycerol (group B), EDAC (group C), and EDAC and 95% glycerol (group D)
      respectively. The treated ABPs were implanted subcutaneously in the back of SD
      rats respectively at random and no material was implanted as control. Seven rats
      were sacrificed at 2 weeks, twelve at 4 weeks, twelve at 8 weeks, seven at 16
      weeks. Local reaction was studied grossly. The amount of antigen presenting cell
      (APC) and the percentage of ABP degeneration were reckoned by images analysis
      system. RESULTS: The ABPs were replaced by fibroblasts completely in group A at 8
      weeks, in group C at 16 weeks, but only less than 50% till 16 weeks in groups B
      and D. In all groups, the depth of surrounding fibres attenuated time
      dependently. The APC amount of the groups B and D was higher than that of the
      control group, and the ABP of the groups B and D degraded partly at 16 weeks.
      CONCLUSION: The ABP treated with EDAC can be replaced by the surrounding tissues
      and has good biocompatibility.

PMID- 16579245
TI  - [Elastic modulus of small intestinal submucosa].
AB  - OBJECTIVE: to determine the modulus of elasticity (E) of small intestinal
      submucosa (SIS), a new biological graft material. METHODS: The longitudinal
      tensile testing was performed on 21 specimens of canine jejunum with the
      electronic material test machine. RESULTS: Stress (sigma)-strain (epsilon) data
      were obtained. It was found that the stress (sigma)-strain (epsilon) data fitted
      the expression sigma = Kiepsilon(alpha) very well, the mean correlation
      coefficients R2 was 0. 991 6. Then the expression of the modulus of elasticity
      (E) of SIS was E=K(1/alpha)sigma(1-1/alpha). The mean values of alpha and K were
      3.966 9 and 374.55, so E = 4.3992sigma(0.75). CONCLUSION: The modulus of
      elasticity was found to increase with increasing stress. The variations law is
      similar to that of the vessels. Furthermore when sigma is 0.01333 MPa (100 mmHg),
      E is about 0.16 MPa, which is similar to that of the vessels.

PMID- 16579246
TI  - [An experimental study on homologous vascularized nerve transplantation after
      ultra deep cryopreservation].
AB  - OBJECTIVE: To study the feasibility of homologous vascularized nerve
      transplantation after ultra deep cryopreservation. METHODS: Vascularized sciatic
      nerve from 12 female dogs was transplanted after ultra deep cryopreservation.
      Forty-eight male dogs were divided into 4 groups: ultra deep cryopreservation
      homologous vascularized nerve (group A), ultra deep cryopreservation homologous
      nerve (group B), fresh homologous vascularized nerve (group C), and fresh
      autologous vascularized nerve (group D). The gross appearance, patency rate of
      artery and morphological transplanted nerve were observed 1, 4 and 12 weeks after
      transplantation respectively. Immunological analysis was performed using IL-2
      assay and T lymphocyte subpopulations assay after 4 weeks. Image pattern analysis
      and electromyogram were observed after 12 weeks. RESULTS: In groups A and D, no
      toe ulcer occurred, the atrophy of later limb and the sense of pain from skin of
      calf were restore significantly in the postoperative 12th week. In groups B and
      C, toe ulcer occurred, the atrophy of later limb and the sense of pain from skin
      of calf were not restored significantly in the postoperative 12th week. The
      vessel patency rate of groups A and D was 83.3%, which was significantly higher
      than that of group C (50%, P < 0.05). The changes of IL-2 and Th, Ts in group C
      were significantly higher than that in groups A, B, D (P < 0.01). There were
      increased vessel and regenerated nerve in transplanted nerve under optical
      microscope and image pattern analysis in groups A and D. There were shorter
      latent period of motor evoked potential, greater amplitude of action potential
      and faster motor nerve conducting velocity in groups A and D after 12 weeks.
      CONCLUSION: The antigenicity of the homologous never and vessel may be reduced
      significantly by being frozen, and cryopreserved vascularized nerve can
      transferred successfully without the use of immunosuppressive agents.
      Vascularized nerve may restore good significantly for the thick nerve.

PMID- 16579247
TI  - Wanted: surgical education.

PMID- 16579248
TI  - Trauma in pregnancy: assessment and treatment.
AB  - Women between the ages of 10 and 50 year-old have the potential for pregnancy;
      therefore this condition must be taken into consideration when a woman is
      examined in the Emergency Room after sustaining a traumatic event. Pregnancy
      produces significant physiologic and anatomic changes in every system of the
      female body. The evaluation of the traumatized pregnant patient, the approach,
      and the interpretation of the diagnostic tests results must be accompanied by the
      full knowledge of all changes that take place during pregnancy. In the same
      context, although the physician treating a pregnant trauma victim must remember
      that there are two patients, the treatment priorities are the same as for the non
      pregnant trauma patient. The best initial treatment for the fetus is the optimum
      resuscitation of the mother. A thorough exam should take place to discover unique
      conditions that might be present in any pregnant patient such as blunt or
      penetrating injury to the uterus, placental abruption, amniotic fluid embolism,
      isoimmunization, and premature rupture of membranes. The obstetrician should be
      present at all times and be considered a part of the trauma team in the
      evaluation and treatment of a pregnant trauma patient.

PMID- 16579249
TI  - Pyloroplasty for benign gastric outlet obstruction--indications and techniques.
AB  - The understanding of peptic ulcer disease (PUD) etiology, and improvements in
      treatment during the last two decades, has dramatically decreased the once so
      frequently performed procedures for PUD and its complications. Benign gastric
      outlet obstruction may, however, still require operative intervention when non
      operative treatment fails. Today, surgeons in training, and even practicing
      surgeons, may have limited operative experience with procedures required to
      alleviate an obstructed pylorus. Our aim of this paper is to review the
      techniques (the Heineke-Mikulicz and Finney pyloroplasties, and modifications)
      and indications for pyloroplasty in the modern surgical era.

PMID- 16579250
TI  - Postoperative physical training following colorectal surgery: a randomised,
      placebo-controlled study.
AB  - BACKGROUND AND AIMS: Major surgery is often followed by fatigue and reduced
      physical function. We wished to study if postoperative physical training reduced
      fatigue and improved physical function. MATERIAL AND METHODS: Randomised, placebo
      controlled, single-blinded study. Participants were unselected patients > or = 60
      years undergoing elective colorectal surgery without disseminated cancer or
      inflammatory bowel disease. Group A trained muscular strength and work capacity.
      Group B performed relaxation exercises and received hot wrappings and massage.
      Main outcome measures were: fatigue (visual analogue scale), muscular strength,
      walking speed, physical performance test, and physical function questions (SF
      36). RESULTS: Preoperatively the two groups were similar except that A was more
      fatigued than B. By postoperative day seven fatigue had increased compared to
      preoperatively, more in B than A, but by day 30 and 90 there were no significant
      differences between groups. All indices of physical function decreased
      postoperative day seven and were at the preoperative level day 90 with no
      significant differences between groups in change in function. Day seven the
      change in knee extension strength tended to be lower in B than A but by day 30
      changes were similar in both groups. CONCLUSION: Postoperative training did not
      improve physical function, but reduced fatigue in hospital.

PMID- 16579251
TI  - Stoma care problems after stoma surgery in Northern Finland.
AB  - BACKGROUND AND AIMS: Stoma-related complications and problems in stoma care are
      common after gastrointestinal surgery requiring the construction of a stoma. The
      frequency and types of such complications and problems were evaluated in a
      patient cohort operated on in Oulu University Hospital. MATERIAL AND METHODS: A
      detailed questionnaire concerning clinical problems and stoma care was mailed to
      163 stoma patients operated on during the years from 1995 to 2001 in Oulu
      University Hospital. One hundred and nineteen patients (70 percent) answered the
      questions adequately. The clinical variables concerning stoma complications and
      the patients' symptoms, problems with stoma care and adaptation to the situation
      were recorded. Special attention was paid to the patients' general wellbeing and
      social problems. RESULTS: Thirty-five patients (30%) had stoma complications,
      most commonly parastomal hernias (18 cases). Patients with an ileostomy had more
      difficulties with stoma handling more often than the patients with a colostomy.
      Seventy-eight patients (66%) were well adapted to their stoma, including 49 (72%)
      of the patients with a colostomy and 25 (56%) of the patients with an ileostomy.
      Of the 41 non-adapted patients, 12 did not accept their altered body image, ten
      had problems in social life and nine had difficulties because of faecal leakage.
      The quality of life analysis of 114 patients showed that their physical condition
      was better than before the operation in 55 cases (48%), unchanged in 16 (14%) and
      worse in 43 (38%). General mental health was better than before the operation in
      52 cases (46%), unchanged in 23 (20%) and worse in 39 (34%) patients. Social
      functioning had improved after stoma surgery in 38 cases (34%), remained
      unchanged in 27 (24%) and deteriorated in 46 (42%) patients after stoma surgery.
      Patients with a colostomy reported worse subjective physical condition, mental
      health and social functioning than the patients with an ileostomy. CONCLUSIONS:
      Two-thirds of the patients had adapted to their stoma. The patients with an
      ileostomy had difficulties in stoma handling and the patients with a colostomy
      reported their physical, mental and social wellbeing to be affected.

PMID- 16579252
TI  - Does rapid intraoperative parathyroid hormone analysis predict cure in patients
      undergoing surgery for primary hyperparathyroidism? A prospective study.
AB  - BACKGROUND AND AIMS: Preoperative 99mTc-sestamibi scintigraphy is used by many
      surgeons to identify the anatomical location of pathological parathyroid glands
      in patients undergoing surgical treatment for hyperparathyroidism. However, false
      negative results do occur. It has been suggested that intraoperative parathyroid
      hormone (PTH) analysis may enhance the possibility of performing successful
      focused, unilateral neck surgery in these patients. This study aimed to evaluate
      whether an adequate fall in intraoperative parathyroid hormone values predicts
      the removal of all hyperfunctioning parathyroid tissue and postoperative
      normocalcemia. MATERIAL AND METHODS: One hundred consecutive patients undergoing
      surgery for hyperparathyroidism had preoperative 99mTc-sestamibi scintigraphy and
      intraoperative parathyroid hormone (PTH) analysis. A fall in intraoperative PTH
      value by more than 50% of baseline value ended the procedure. This prospective
      study presents the clinical and biochemical results. RESULTS: The overall
      sensitivity of the 99mTc-sestamib scintigraphy was 88% and for single adenomas
      95%. The scintigraphy failed to detect the correct pathology in all cases with
      multiglandular disease (7 patients). A fall in intraoperative PTH value by more
      than 50% of baseline value was achieved in all patients. The combination of
      intraoperative PTH analysis and 99mTc-sestamibi scintigraphy enabled us to limit
      the operation to a focused, unilateral operation in 87 of the 100 patients. All
      patients were normocalcemic postoperatively. CONCLUSIONS: A fall in
      intraoperative PTH value more than 50 % of baseline value seems to predict
      postoperative normocalcemia and the removal of all hyperfunctioning parathyroid
      tissue. Bilateral neck exploration is avoided in the majority of patients.

PMID- 16579253
TI  - Results and future of carotid endarterectomy in a medium-sized Finnish central
      hospital.
AB  - BACKGROUND AND AIMS: Carotid endarterectomies (CEA) should, by general agreement,
      be performed only at specialised institutions and on patients who are expected to
      have a low rate of complications, i.e., a 6% surgical risk for patients with
      symptomatic and a 3% risk for patients with asymptomatic carotid artery disease.
      We have reviewed the midterm results after CEA in a medium-sized Finnish central
      hospital to audit whether our results fulfil current quality standards. PATIENTS,
      MATERIALS AND METHODS: There were 116 consecutively operated patients at the
      Paijat-Hame Central Hospital during the years 1999-2003 on whom 122 CEAs were
      made. All CEAs were performed by conventional methods and shunts and patches were
      used when necessary. RESULTS: The overall survival rate was 81.0% during the 3.6
      +/- 1.5 years [range 1.3-6.3 years] follow-up. The incidence of early major
      stroke was 2.5% and of late major stroke 1.6%. Other complications included
      cranial nerve deficit (2.5%), wound haematoma (3.3%) and postoperative
      hypertension (3.3%) or hypotension (2.5%). Significant changes in medication were
      needed after surgery in several patient subgroups. CONCLUSIONS: The results of
      CEA at the Paijat-Hame Central Hospital are at least acceptable. The primary
      prevention of strokes with pharmacotherapy needs aggressive improvement.

PMID- 16579254
TI  - Red blood cell transfusions in patients undergoing lower extremity artery bypass
      surgery.
AB  - BACKGROUND AND AIMS: The purpose of this study was to search predictors of red
      blood cell transfusions in peripheral vascular surgical patients. MATERIAL AND
      METHODS: All the patients who undergone infrainguinal bypass surgery at Helsinki
      University Hospital in the year 2000 were included. Of 266 records 261 (98%) were
      available for data review. Multiple stepwise regression model was created to
      identify independent predictors of blood use. RESULTS AND CONCLUSIONS: 174 (67%)
      of the patients received red blood cell transfusion. The lowest measured mean
      (SD) haemoglobin was 94 (11) g/l intraoperatively and 92 (+/- 10) g/l on the
      first two postoperative days. The median (range) number of units was 3 (1-19).
      Multivariate analysis showed that high age (p = 0.019), small body surface area
      (p = 0.017), low preoperative haemoglobin (p < 0.001), blood loss (p < 0.001),
      long lasting surgery (p<0.001), reoperation (p=0.018), femoro-distal
      reconstruction (p=0.048) and chronic obstructive pulmonary disease (p = 0.023)
      increased the risk to receive red blood cell transfusion. The frequent use of
      antithrombotic medication (72% of the patients) did not significantly increase
      red blood cell administration. The generous use of red blood cells despite
      relative safe haemoglobin levels indicates a need for a standardized
      multidisciplinary transfusion strategy in this patient population. Otherwise,
      most of the predictors for red blood cell administration were nonmodifiable.

PMID- 16579255
TI  - Service comparison between vascular and general surgery in the treatment of
      chronic venous insufficiency with special reference to preoperative Doppler
      techniques.
AB  - AIMS: To compare the ability of vascular and general surgical services to abolish
      reflux in superficial venous system with a special reference to preoperative use
      of Doppler techniques. MATERIALS AND METHODS: 68 lower limbs operated on for
      venous insufficiency based on either preoperative Duplex evaluation and Doppler
      marking in a vascular surgical unit (Vascular Surgical Service, VSS: 33 limbs,
      clinical class C2-C6) or clinical findings in a general surgical unit (General
      Surgical Service, GSS: 35 limbs, clinical class C2-C4) were re-examined
      clinically and with duplex scanning for reflux some three years postoperatively.
      RESULTS: Marked superficial or perforator vein reflux was observed in 27 of 68
      (39.7 %) operated limbs, thirteen of which in VSS and fourteen in GSS. However,
      axial reflux at saphenofemoral or thigh level was observed significantly less in
      VSS compared to GSS (3 vs 13, p = 0,006). CONCLUSION: Total ablation of any
      reflux appeared difficult irrespective of the preoperative assessment.
      Preoperative Duplex examination, however, aided in identifying and treating axial
      reflux at thigh level.

PMID- 16579256
TI  - Severe vascular gunshot injuries of the extremities: a ten-year nation-wide
      analysis from Finland.
AB  - BACKGROUND AND AIMS: Gunshot wounds affecting the main vessels of the extremities
      mostly threaten limb salvage. The purpose of this study was to analyse the nature
      and severity of civilian vascular gunshot injuries of the extremities using a
      nation-wide database. MATERIAL AND METHODS: Retrospective analysis of the Finnish
      Hospital Discharge Register, hospital records and death certificates over a 10
      year period from January 1, 1990 to December 31, 1999. RESULTS: Thirty-two
      individuals with the mean age of 33 years (17-68) sustained 43 severe vascular
      injuries to the extremities caused by gunshots. The incidence was 6.0 (95% CI:
      4.1-8.5) per 10,000,000 person-years and did not change significantly during the
      period. Four of the injured died. The most common anatomical locations of
      vascular injuries were the femoral artery (6 lesions), popliteal artery (6) and
      superficial femoral artery (5). Use of alcohol was detected in ten cases (32% of
      patients) and of illegal drugs in seven cases (22%). Five patients (18% of non
      fatal injuries) required vascular re-operation caused by post-operative problems.
      Five amputations were performed as primary treatment. CONCLUSIONS: Severe
      vascular gunshot injuries of the extremities are not common in Finland. The need
      for primary amputation or vascular re-operations is noteworthy.

PMID- 16579257
TI  - Unrestricted weight bearing and intensive physiotherapy after uncemented total
      hip arthroplasty.
AB  - BACKGROUND AND AIMS: The effectiveness of partial weightbearing after hip surgery
      has been questioned as well as the need of intensive physiotherapy. MATERIAL AND
      METHODS: 36 patients (average age 54.4, 19 women) operated with uncemented hip
      arthroplasty were randomized either to unrestricted weightbearing (UWB) combined
      with intensive physiotherapy or to partial weightbearing (PWB) for 3 months
      combined with a short self-training program. The load during walking and the
      muscle strength (MS) in abduction was measured preoperative and subsequent up to
      12 months. RESULTS: The average peak load on the operated leg at one week was
      39.0 kg for the UWB and 25.8 for the PWB group (P = 0.009) while at three months
      70.0 and 31.7 (P = 0.001) respectively. At 6 and 12 months there were no
      differences between the groups. The muscle strength increased in both groups up
      to six months but there were no differences between the groups. CONCLUSIONS: Even
      though patients applied more load than the recommended 15 kg most patients were
      able to comply with partial weightbearing fairly well. The effect of intensive
      physiotherapy on the muscle strength after hip arthroplasty is questionable.

PMID- 16579258
TI  - Hip fracture treatment in Oulu--one-year survey with four-month follow-up.
AB  - BACKGROUNDS AND AIMS: The standardized forms of the Standardized Audit of Hip
      Fractures in Europe (SAHFE) are aimed for the evaluation of hip fracture
      treatment in different hospitals and countries. The purpose was to evaluate and
      characterize a cohort of hip fracture patients with these forms and to evaluate
      their value in quality control. MATERIAL AND METHODS: The non-pathological hip
      fractures in patients over 49 years of age treated in the Oulu University
      Hospital were prospectively recorded during a one-year period using SAHFE forms.
      RESULTS: There were 238 (52 male and 186 female) patients with a mean age of 78
      (50-102) years. Fifty-nine percent of the patients were admitted from their own
      homes. Fifty-seven percent were able to walk alone outdoors and 48% could walk
      without walking aids before the fracture. A hundred and fifty patients had
      cervical fractures and 88 trochanteric fractures. The most frequent treatment of
      cervical fractures was Austin-Moore hemiarthroplasty (68%) and that of
      trochanteric fractures Gamma nail fixation (86%). At four months after the
      fracture, 50% lived in their own homes, 33% could walk alone outdoors and 13%
      could walk without any aids. Thirty-two percent had no pain in the hip. The
      overall mortality at four months was 17.6% and that of the operated patients
      16.2%. The reoperation rate was 8.5%. CONCLUSION: SAHFE forms were very useful in
      the evaluation of the quality of the hip fracture treatment.

PMID- 16579260
TI  - SJS--one for all, and all for one!

PMID- 16579259
TI  - Recovery of muscle strength after late repair of distal biceps brachii tendon.
AB  - BACKGROUND AND AIMS: Ruptures of the distal part of the biceps brachii tendon are
      rare. The diagnosis is often delayed and only late repair can be considered. In
      this study, the recovery of muscle strength after late repair of the distal
      biceps brachii tendon was evaluated. MATERIALS AND METHODS: Sixteen patients with
      a ruptured distal biceps brachii tendon were analysed. The mean delay from the
      primary trauma to the operation was 35 weeks. The tendon was anatomically re
      attached with bone anchors. In three cases a tendon graft was needed. The
      operated arms were immobilised postoperatively for four weeks, after which
      mobilisation was allowed. Maximal static flexion and supination strength was
      measured after an average follow-up time of 124 weeks by using a computer-based
      isokinetic dynamometer. RESULTS: Patient satisfaction and overall muscle strength
      recovery were very good. Compared to the non-operated side, average flexion
      strength recovery was 90% and corresponding recovery of supination strength 78%.
      Weakness on supination remained in the cases where a tendon graft was used. One
      patient needed a re-operation for a re-rupture. There were three cases of
      transient paresthesia of the cutaneous nerve. All patients resumed their previous
      work. CONCLUSION: Late anatomical repair of the biceps brachii tendon restores
      very good flexion and moderate supination strength. This operation should always
      be considered when the primary diagnosis is delayed.

PMID- 16579262
TI  - How to select a vendor based on practice-specific requirements: developing your
      RFI and RFP.
AB  - Developing an RFP can be a time-consuming process if you allow it to get out of
      control. The key is to keep the process simple by prioritizing what is most
      important and to use the RFI to get to your top vendor options quickly. Early
      planning and preparation will pay off in more ways than one. For a complimentary
      example of an RFI and RFP, please contact The Coker Group at www.cokergroup.com.

PMID- 16579261
TI  - Preparing your practice for EMR: are you ready?
AB  - Practices considering an EMR system purchase and implementation must first
      consider if the practice is ready to undertake a project of this size and
      magnitude, with such far-reaching implications for the organization. Before
      considering EMR, an evaluation of the existing PM system is in order.
      Incorporating an EMR system when the PM system is inadequate decreases ROI,
      minimizes the efficiencies gained through EMR and ultimately may not support the
      long-term goals of the practice. The first step for any group or solo medical
      practice is to understand itself: what are the practice's goals; where will the
      practice be in terms of maturity, market share, and community presence in five or
      10 years; what are the requirements for a system to support the needs and goals
      of the practice? Understanding each of these aspects improves the negotiating
      strength of the practice, ensures a successful implementation plan, and decreases
      the time to return on objective and subsequent ROI.

PMID- 16579264
TI  - How to motivate physicians and develop a physician champion.
AB  - Physician champions and leaders are essential to the success ofa CCIS
      implementation. Physician champions or leaders can be developed by recognizing
      the qualities of a leader and cultivating them. Finally, sustainable second-order
      change is facilitated bv a transformational leader--a leader who is charismatic,
      considers individual characteristics and needs of the constituency, and
      stimulates the constituency intellectually. A transformational leader does not
      accept the status quo but rather is continually questioning and offering
      constructive problem solutions. Transformational leadership may require more
      patience, time, tolerance, and resources, but it is worth the effort.

PMID- 16579263
TI  - Why and how to develop an internal selection committee for EMR.
AB  - Educating and informing the practice staff; developing your selection committee
      through careful consideration of participants; conducting the committee's work
      through structured processes; and engaging and visible leadership and support
      from management are the foundation for EMR selection. Following these guidelines
      will help to ensure the success of the committee and subsequent installation of a
      new EMR system.

PMID- 16579265
TI  - How to handle sales demo, reference checks, and site visits.
AB  - Although challenging and time consuming, vendor selection, product
      demonstrations, reference checks, and site visits can be streamlined by following
      the guidelines and steps presented here. A systematic and uniform approach is the
      best way to save time and achieve the desired results that are so important to
      your practice.

PMID- 16579266
TI  - How to negotiate a performance-based EMR system contract.

PMID- 16579267
TI  - EMR: financial considerations.

PMID- 16579268
TI  - How to ensure future compatibility and ensure that your vendor meets government
      mandated standards.

PMID- 16579269
TI  - How to avoid costly EMR purchasing mistakes.

PMID- 16579270
TI  - Implementing and adopting a computerized clinical information system.

PMID- 16579271
TI  - Is your technology infrastructure HIPAA compliant?

PMID- 16579272
TI  - Using the Internet and E-mail appropriately in the medical practice.

PMID- 16579273
TI  - Network security.
AB  - As you can see, there are a number of different ways to protect your network with
      different protocols, all of which can be very confusing to people whose core
      business process is not technology. This article is only a brief synopsis of the
      dangers that lurk in the corners of the technology world. Therefore, the best
      course of action is to do as much research as possible rather than falling into a
      situation of risk and vulnerability by implementing a system or network that does
      not work with your business. Remember, the technology is there to support your
      business; the business should not have to work around the technology.

PMID- 16579274
TI  - Mitigating risk: IT disaster recovery.

PMID- 16579275
TI  - Procuring hardware for your EMR system.

PMID- 16579277
TI  - Coding and EMR: what your vendor won't tell you.

PMID- 16579276
TI  - The future of health care policy.

PMID- 16579278
TI  - Weighing the risks. More than ever, obese patients are turning to gastric bypass
      surgery. the results can be striking, but it's not a slam-dunk.

PMID- 16579279
TI  - A tribute to United States Senator Debbie Stabenow.

PMID- 16579280
TI  - Competition in homecare & hospice.

PMID- 16579282
TI  - Revisiting patient admission and discharge processes in today's homecare
      environment.

PMID- 16579281
TI  - You have rights when responding to a claims overpayment.
AB  - This article summarized many of the defenses available to a provider faced with
      an overpayment determination. These issues are complex and providers may benefit
      from consultation with knowledgeable counsel.

PMID- 16579283
TI  - QAPI: a new way to manage hospice quality.

PMID- 16579284
TI  - Legal ramifications of per visit pay in the USA.
AB  - Agencies, which are subject to the FLSA, (Fair Labor Standards Act), must pay
      their covered employees the minimum wage required by law and overtime pay at a
      rate of one-and-one-half times the employee's regular hourly rate for hours
      worked in excess of forty hours in a work week. Failure to do so can result in
      substantial liability for not only the unpaid wages, but for significant
      penalties and the employee's attorney's fees as well.

PMID- 16579285
TI  - Balancing provider, worker and consumer interests.

PMID- 16579286
TI  - Promoting home health care technology. Changes in federal fraud regulations may
      provide more flexibility.

PMID- 16579287
TI  - The data is in: best home care marketing practices revealed. Part Two.

PMID- 16579288
TI  - The Briggs National Quality Improvement/Hospitalization Reduction Study.

PMID- 16579289
TI  - Since 911, where has the urgency gone? Are we really prepared?
AB  - From Are We Really Prepared?--Part I in CARING's last issue, it was determined
      that all agencies have updated their emergency preparedness plans. However,
      Universal ID Cards for home health care workers do not exist at this time. The
      study also revealed that most agencies have not increased inter-agency
      cooperation. In Part II of this study, we learned that some agencies have
      improved their communication capabilities whereas others remain limited in their
      attempts to upgrade to this recommendation. Transportation issues during an
      emergency/disaster situation continue to be a major area of concern for all
      homecare providers. The agencies that appeared to be best prepared for an
      emergency were the larger home care providers with the most resources, both
      technical and financial. While the larger agencies still remain vulnerable in an
      emergency situation, the smaller, less technically and financially equipped
      agencies would benefit from partnering with the larger home care companies.
      Critical to any emergency preparedness and response endeavor is the capacity to
      maintain or re-establish a "command operations center", and to insure the ability
      of essential employees to communicate with each other in an attempt to direct or
      redirect caregivers to their highest priority patients. Engaging the assistance
      of patients' families, significant others, and emergency contacts is crucial in
      our endeavor to be prepared for all emergency and catastrophic events. In
      addition, because the transportation infrastructure, power grid and communication
      network all continue to be susceptible to failure, insuring that critical
      personnel (especially direct care workers) have a personal family emergency back
      up plan in place increases the likelihood of successfully responding to an
      emergency or disaster, and fulfilling the central mission of the home care
      provider--maintaining continuity of services to all patients. Considering
      governmental failures in responding to the hurricanes in Florida and the Gulf
      Coast, it becomes paramount for every individual to develop contingency plans for
      any and all emergency/disaster events.

PMID- 16579290
TI  - Supreme Court votes to uphold Oregon assisted suicide law.

PMID- 16579291
TI  - Hospices choose legislative and regulatory priorities for 2006. Ensuring access
      to pain control medications tops both lists.

PMID- 16579292
TI  - Taking stock.

PMID- 16579293
TI  - Private pay home care; serving wealthy Americans.

PMID- 16579294
TI  - Law: the ultimate public service.

PMID- 16579295
TI  - "Show me the money". Testimony for sale: another type of 'tart' reform needed.

PMID- 16579296
TI  - The right to a fair trial: the MSMA expert medical witness reform bill of 2006.

PMID- 16579297
TI  - Biomedical research in Missouri: great promise & imminent peril.

PMID- 16579298
TI  - Medical malpractice insurance: the implications and complications.

PMID- 16579299
TI  - A decade of humanitarian aid and medical knowledge exchange between Missouri and
      European Georgia physicians.
AB  - Missouri physicians have shared humanitarian aid and exchanged medical knowledge
      for the past decade with European Georgia physicians. Donations have been made of
      medications, medical publications, used equipment and supplies as well as
      organizational knowledge exchange with sister medical organizations, sister
      medical schools and sister cities. The medical specialty exchanges include family
      medicine, neonatology, pediatrics, diabetology, endocrinology, ophthalmology,
      obstetrics, gynecology, anesthesiology and surgery.

PMID- 16579301
TI  - Doctor's orders: talk prevention and they will listen.

PMID- 16579300
TI  - Dietetics: integration into modern clinical medicine.
AB  - Registered dietitians have unique expertise in foods and nutrition. They are able
      and willing to integrate diet and nutrition with modern clinical medicine for the
      betterment of your patients' health. The RD's services at present are often
      incompletely understood and underutilized. Physicians would do well to make the
      dietitian a valued and often used member of the healthcare team.

PMID- 16579302
TI  - Current issues in health care: how Missouri physicians see it.

PMID- 16579303
TI  - Pain therapy outdated.

PMID- 16579304
TI  - Saving Medicaid.

PMID- 16579305
TI  - Pediatric updates and the National Children's Study.

PMID- 16579306
TI  - Redesigning the health care system of the future.
AB  - The models outlined above represent alternative constructs for examining factors
      that may or may not influence human health in a positive manner. If the economic
      framework seems more theoretical than actionable, consider an alternative
      framework that has been advanced by the American Hospital Association and
      described in Table I. Regardless of the framework adopted, work to improve the
      health care system and its financing will be hard, irrespective of whether
      incremental or wholesale changes are made. What is important, however, is that a
      thoughtful approach be taken and the trade-offs of each decision carefully
      weighted. The health of the population of the state and the country depend on it.

PMID- 16579307
TI  - Recent advances in asthma management.
AB  - Effective asthma management requires that the diagnosis be made, even if the
      patient is very young and incapable of doing a pulmonary function test. Agreement
      on the goals of treatment between the patient and provider leads to a set of
      outcomes that can be used to measure the effectiveness of treatment and to modify
      it if needed. The most important component of asthma management is for patients
      to have a written asthma action plan that guides them to increase treatment when
      the asthma flares and reduce treatment when it gets better. With early diagnosis
      and effective treatment it should be possible for patients who have asthma to
      live normal lives.

PMID- 16579308
TI  - Are we in the midst of an autism epidemic? A review of prevalence data.
AB  - Autism is a "developmental disorder of neurobiologic origin that is defined on
      the basis of developmental and behavioral features." Studies over the past 10-15
      years suggest that the prevalence of autism is rising. Media coverage has been
      extensive and has indicated the presence of an "autism epidemic." The goal of
      this article is to review relevant epidemiologic studies which address the
      prevalence of Autistic Spectrum Disorders in the last 30 years.

PMID- 16579309
TI  - Chronic abdominal pain in children: an update.
AB  - Despite the fact that chronic abdominal pain is a common complaint in children
      and adolescents, the complexity of this condition only recently has begun to be
      understood. This article summarizes new advances in the diagnosis,
      conceptualization, and treatment of chronic abdominal pain. Implications for
      effective assessment and treatment within the pediatric primary care setting are
      discussed.

PMID- 16579310
TI  - Methicillin-resistant Staphylococcus aureus infections in children.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infections are an emerging
      problem in both children and adults throughout the United States. Skin and soft
      tissue infections are most common, however serious invasive disease can occur and
      may involve any anatomic site. The initial empiric therapy of suspected S. aureus
      infections will be influenced by the regional antimicrobial susceptibility
      patterns for the organism as well as the severity of the infection being treated.
      This article will review the epidemiology, clinical features, and treatment
      considerations for MRSA infections in children.

PMID- 16579311
TI  - Overuse injuries in the pediatric and adolescent athlete.
AB  - A growing number of pediatric orthopedic patients fall into two dissimilar
      groups: the obese patient with problems related to obesity, and the young athlete
      injured during sports. While there is widespread recognition of pediatric
      orthopedic diseases related to obesity, the injuries resulting from "overuse" or
      over participation in sports are less understood and recognized. The majority of
      athletes involved in team sports in the Unites States are grade school and
      interscholastic athletes. The motivation for participation in sports varies
      greatly. Young athletes at risk for injury include the reluctant athlete who is
      not in the aerobic condition necessary to participate in sports, the eager
      athlete who initiates participation too vigorously, and the ambitious athlete who
      chronically "overtrains".

PMID- 16579315
TI  - Genetic counseling and disclosure of results.

PMID- 16579316
TI  - Eliminating mandatory overtime.

PMID- 16579317
TI  - Preventing and terminating unwanted pregnancies in Turkey.
AB  - PURPOSE: To determine the methods used to prevent pregnancy by women seeking
      abortion of unwanted pregnancy, their knowledge and use of emergency
      contraception, and reasons for wanting the abortion. DESIGN: The sample was 144
      randomly selected women, who requested abortion for termination of their
      pregnancies at two hospitals in Izmir, Turkey, during the study period. METHODS:
      A questionnaire was completed by the researcher in face-to-face interviews.
      FINDINGS: In this sample 43.8% had had previous abortions; 77.1% used some method
      of family planning; 7.0% used emergency contraceptives. The methods selected
      after unprotected sexual intercourse by these women included vaginal douche
      (37.5%), waiting to see whether the menstrual cycle would begin (27.0%), going to
      a hospital or maternal-child health center (24.3%), and two other alternatives
      (4.2%). One-fifth of the women said that, if they get pregnant again, they will
      have another abortion. CONCLUSIONS: The number of unwanted pregnancies is high
      and many women seek abortions as a birth control method. Women in this sample
      needed information about effective methods for preventing pregnancy.

PMID- 16579318
TI  - Genomics, nutrition, obesity, and diabetes.
AB  - PURPOSE: To present evidence of genetic and environmental interactions as they
      relate to nutrition, diabetes, and obesity. METHODS: A review of seminal
      literature related to genetics, obesity, and diabetes. FINDINGS: Multifactorial
      interactions are important in the development of nutrition-related disorders, but
      the challenge remains to explain how these interactions are expressed. Treating
      subpopulations of people might be important and useful to some extent at present,
      but in the future treating people of given genetic predispositions and other
      personal and environmental factors will have greater effects on quality-of-life
      indicators and life expectancies. CONCLUSIONS: Individualization coupled with
      multifactorial interactions will lead to new and more effective preventive and
      treatment modalities of nutrition-related disorders. With obesity and diabetes,
      genomics will bridge the traditional use of diet, exercise, and weight reduction
      with other environmental factors, ultimately leading to healthier lives.

PMID- 16579319
TI  - Factor V Leiden as a common genetic risk factor for venous thromboembolism.
AB  - PURPOSE: To increase nurses' knowledge of the Factor V Leiden (FVL) genetic trait
      for venous thromboembolism. ORGANIZING FRAMEWORK: An overview of the history,
      prevalence, and predisposition of the FVL genetic mutation, including who should
      be tested and how and in what circumstances people with FVL should be treated.
      FINDINGS: FVL is the most commonly recognized genetic trait associated with
      venous thrombosis. It is found predominantly in Caucasian populations.
      Biochemically it causes "activated protein C resistance (APCR)." The decision to
      test for FVL depends on whether the information gained will potentially improve
      the health care of the person or family. For people who have had deep venous
      thrombosis, testing for FVL will likely not alter treatment approaches. Currently
      the advantage for testing is primarily limited to asymptomatic family members who
      carry FVL and who have had deep vein thrombosis. Close relatives who also carry
      the mutated gene might benefit from prophylactic anticoagulation when their risk
      of thrombosis is increased by temporary factors such as surgery. CONCLUSIONS:
      Nurses are in a unique position to provide accurate information and counseling
      when patients and their family members are presented with the results of
      thrombophilia testing.

PMID- 16579320
TI  - Postpartum smoking relapse and becoming a mother.
AB  - PURPOSE: To propose an innovative, theoretically-derived conceptual framework for
      studies of postpartum smoking relapse including concepts of smoking abstinence
      self-efficacy and becoming a mother. METHODS: Presentation of an existing
      research paradigm followed by evidence from intervention research and studies of
      factors associated with postpartum smoking behavior, leading to a new approach to
      postpartum smoking relapse. FINDINGS: Effectiveness of current interventions to
      prevent relapse is limited. Variables associated with becoming a mother are
      missing from studies of postpartum smoking relapse. CONCLUSIONS: Context-specific
      variables that influence a woman's progression through the stages of becoming a
      mother might include protective or risk factors that should be incorporated into
      the design of postpartum smoking relapse studies.

PMID- 16579321
TI  - Comparison of health-promoting behaviors of noninstitutionalized and
      institutionalized older adults in Korea.
AB  - PURPOSE: To compare the health-promoting behaviors of noninstitutionalized and
      institutionalized Korean older adults. DESIGN: Descriptive survey. METHODS: The
      study sample included 214 Korean older adults (108 noninstitutionalized and 106
      institutionalized) aged 65 years or over living in Seoul and Daegu, Korea. Data
      were collected from April to August, 2003. Measures were the Health Promoting
      Lifestyle Profile (HPLP), the Rosenberg Self-Esteem Scale (RSES), and the General
      Self-Efficacy Scale. FINDINGS: The average scores for HPLP, self-esteem, and self
      efficacy of noninstitutionalized older adults were higher than those of
      institutionalized participants. Noninstitutionalized participants also scored
      significantly higher than did the institutionalized participants on self-esteem
      and self-efficacy. CONCLUSIONS: Studies were focused on the effects of various
      nursing interventions for health promotion are needed for older adults,
      especially those in institutions.

PMID- 16579322
TI  - Dimensions of professional labor support for intrapartum practice.
AB  - PURPOSE: To define and describe the dimensions of Professional Labor Support
      (PLS). DESIGN AND METHODS: A factor-analytic study was conducted with a random
      sample of 146 intrapartum nurses in Texas. Nurses' responses to the Labor Support
      Questionnaire (LSQ) were subjected to principal components analysis and
      descriptive analysis. FINDINGS: A six-factor solution indicated the dimensions of
      PLS: Tangible Support, Advocacy, Emotional Support-Reassurance, Emotional Support
      Creating Control, Security and Comfort, Emotional Support-Nurse Caring Behavior,
      and Informational Support. CONCLUSIONS: Although the presence of four dimensions
      was theorized, six dimensions were found. The emotional support dimension was
      identified by nurses as being an important component of labor support as
      indicated by the identification of three separate emotional support dimensions.

PMID- 16579324
TI  - Perceptions of barriers and benefits to physical activity among outpatients in
      psychiatric rehabilitation.
AB  - PURPOSE: To explore perceived barriers and benefits to physical activity in
      people with serious and persistent mental illness (SPMI) who were enrolled in
      community-based psychiatric rehabilitation. DESIGN AND METHODS: Four focus
      groups, two for men and two for women, were held with a total of 34 outpatients
      from two program sites. The investigators used a semistructured interview guide
      to facilitate the discussions. Audiotapes of the discussions were transcribed and
      analyzed for concepts and themes. FINDINGS: Significant barriers to physical
      activity were: mental illness symptoms, medications, weight gain from
      medications, fear of discrimination, and safety concerns. Being in a psychiatric
      rehabilitation program offered comfort and belonging, but it also had the effect
      of leaving activity initiation up to the program staff, which some participants
      perceived was part of required program compliance. However, participants viewed
      physical activity positively, and they linked being active to improved mental
      health. CONCLUSIONS: Outpatients in psychiatric rehabilitation valued physical
      activity, but mental illness symptoms, medication sedation, weight gain, fear of
      unsafe conditions, fear of discrimination, and interpretations of program
      compliance were barriers. Confronting how attitudes and barriers specific to this
      population can affect activity and reframing program compliance to include the
      independent initiation of activity as part of improving health might help clients
      of mental health services to become more active.

PMID- 16579323
TI  - An intervention study to prevent relapse in patients with schizophrenia.
AB  - PURPOSE: To determine whether the use of relapse prevention plans (RPPs) in
      nursing practice is an effective intervention in reducing relapse rates among
      patients with schizophrenia. DESIGN AND METHODS: Experimental design. Patients
      with schizophrenia (or a related psychotic disorder) and nurses from three mental
      health organizations were randomly assigned to either an experimental (RPP) or
      control condition (care as usual). The primary outcome measure was the psychotic
      relapses in the research groups. RESULTS: The relapse rates in the experimental
      and control groups after 1-year follow-up were 12.5% and 26.2%, respectively (p=.
      12, ns). The relative risk of a relapse in the experimental versus the control
      group was 0.48 (ns). CONCLUSIONS: In this study no statistically significant
      effects of the intervention were found. Effectiveness research in this area
      should be continued with larger sample sizes and longer follow-up periods.

PMID- 16579325
TI  - Integrative review of parenting in nursing research.
AB  - PURPOSE: To synthesize and critically analyze parenting research in nursing.
      DESIGN: Qualitative, integrative review of nursing research studies about
      parenting 1993-2004. METHODS: Studies published by nurse researchers in peer
      reviewed journals were systematically searched using CINAHL and Medline
      databases. Data were organized and analyzed with a sample of 17 nursing research
      studies from core nursing journals. FINDINGS: The majority of parenting research
      has been focused on mothers, primarily about parenting children with physical or
      developmental disabilities. Research about fathers as parents is sparse.
      Parenting across cultures, parenting in the context of family, and theoretical
      frameworks for parenting research are not well developed. CONCLUSIONS: The scope
      of nursing research on parenting is limited. The roles, functions, and contexts
      of parenting are not well defined. Further research is required to describe
      parenting and how parenting affects the health of individuals and families.

PMID- 16579326
TI  - Transitional and health issues of adults with neural tube defects.
AB  - PURPOSE: To examine past, current, and future developmental and health care
      issues and concerns of Caucasian, African American, and Mexican American adults,
      aged 20 to 75 years, with neural tube defects (NTDs). DESIGN: Naturalistic
      inquiry. METHODS: A semi-structured interview was used to obtain information from
      16 Caucasian, 11 African American, and 15 Mexican American adults. FINDINGS:
      Three themes identified in the analysis were uncertainty about the future, access
      to health care and information, and advocacy. CONCLUSIONS: Documenting the adult
      trajectories of chronic childhood conditions, such as NTDs, is important.
      Although much is known about such conditions in childhood, additional knowledge
      about health and developmental concerns across the lifespan enhances provision of
      appropriate anticipatory guidance and health care.

PMID- 16579327
TI  - Factors associated with work satisfaction of registered nurses.
AB  - PURPOSE: To examine the factors that influence the work satisfaction of a
      national sample of registered nurses in metropolitan statistical areas (MSAs).
      DESIGN: A cross-sectional mailed survey design was used. The sample consisted of
      RNs randomly selected from 40 MSAs in 29 states; 1,907 RNs responded (48%). The
      sample of 1,538 RNs working in nursing was used for analysis. METHODS: The
      questionnaire included measures of work attitudes and demographic
      characteristics. The data were analyzed using ordinary least-squares regression.
      FINDINGS: More than 40% of the variance in satisfaction was explained by the
      various work attitudes: supervisor support, work-group cohesion, variety of work,
      autonomy, organizational constraint, promotional opportunities, work and family
      conflict, and distributive justice. RNs who were White, self-perceived as
      healthy, and working in nursing education were more satisfied. RNs that were more
      career oriented were more satisfied. Of the benefits options, only paid time off
      was related to satisfaction. CONCLUSIONS: Work-related factors were significantly
      related to RNs' work satisfaction.

PMID- 16579328
TI  - Nurse care coordination in community-based long-term care.
AB  - PURPOSE: To evaluate the clinical outcomes of a nurse care coordination program
      for people receiving services from a state-funded home and community-based waiver
      program called Missouri Care Options (MCO). DESIGN: A quasi-experimental design
      was used to compare 55 MCO clients who received nurse care coordination (NCC) and
      30 clients who received MCO services but no nurse care coordination. METHODS:
      Nurse care coordination consists of the assignment of a registered nurse who
      provides home care services for both the MCO program and Medicare home health
      services. Two standardized datasets, the Minimum Data Set (MDS) for resident care
      and planning and the Outcome Assessment Instrument and Data Set (OASIS) were
      collected at baseline, 6 months, and 12 months on both groups. Cognition was
      measured with the MDS Cognitive Performance Scale (CPS), activities of daily
      living (ADL) as the sum of five MDS ADL items, depression with the MDS-Depression
      Rating Scale, and incontinence and pressure ulcers with specific MDS items. Three
      OASIS items were used to measure pain, dyspnea, and medication management. The
      Cochran-Mantel-Haenszel (CMH) method was used to test the association between the
      NCC intervention and clinical outcomes. FINDINGS: At 12 months the NCC group
      scored significantly better statistically in the clinical outcomes of pain,
      dyspnea, and ADLs. No significant differences between groups were found in eight
      clinical outcome measures at 6 months. CONCLUSIONS: Use of nurse care
      coordination for acute and chronic home care warrants further evaluation as a
      treatment approach for chronically ill older adults.

PMID- 16579329
TI  - Use of computer technology to enhance immigrant families' adaptation.
AB  - PURPOSE: To summarize how computer technology influenced immigrant families'
      adaptation to life in the United States. DESIGN: Critical ethnography. METHODS:
      Data were collected from 1998 to 2000 from 13 parents and 16 children from nine
      Taiwanese immigrant families using semi-structured interviews and a
      questionnaire. Narrative analysis was used with interview data. FINDINGS:
      Participants faced the demands of language proficiency, economic survival, loss
      of social networks, and social disconnection during resettlement. Computer
      technology provided participants with new occupational opportunities and
      strategies to overcome the barriers and stress created by resettlement. Internet
      and E-mail access greatly facilitated these participant families' adaptation.
      CONCLUSIONS: Study findings warrant further exploration to assess bow new
      computer technology promotes immigrant families' adaptation and alleviates stress
      associated with resettlement, including information about their health and health
      care.

PMID- 16579330
TI  - Nurse dose as a concept.
AB  - PURPOSE: To describe the concept of Nurse Dose. METHODS: The concept of nurse
      dose has been identified from decades of clinical research as a concept essential
      in the delivery of safe and high quality health care. The components of nurse
      dose were conceptualized through review of the literature from nursing, medicine,
      and health services research. FINDINGS: Nurse dose is conceptualized as having
      three equally essential components: dose, nurse, and host and host response. Dose
      in the macro view includes the number of nurses per patient or per population in
      cities, states, regions, or countries. Dose in a micro view includes the amount
      of nurse time and the number of contacts. The nurse component consists of the
      education, expertise, and experience of the nurse. Host is represented by an
      organization and its characteristics (culture, autonomy, practice control) in a
      macro view and by the patient and characteristics (beliefs, values, culture) in a
      micro view. Host response includes response to the autonomy and acceptability of
      the nurse. CONCLUSIONS: Greater nurse dose has been associated with decreases in
      patient mortality, morbidity, and healthcare costs.

PMID- 16579331
TI  - Acceptance of male registered nurses by female registered nurses.
AB  - PURPOSE: To investigate attitudes of acceptance toward male registered nurses by
      female registered nurses. DESIGN: Randomized descriptive design using 105 female
      registered nurses from a large midwestern state in the US. METHODS: Data were
      collected using an attitude inventory and analyzed using t test, chi square,
      Spearman rho, Pearson correlation, Mann-Whitney U and multiple regression tests.
      FINDINGS: Acceptance was normally distributed. No difference in acceptance was
      found between rural and urban participants. The length of time working with a
      male nurse explained significant variance in acceptance scores. City or town of
      socialization was not related to acceptance scores. Rural participants were less
      likely than were urban participants to believe that female nurses are ready to
      accept large numbers of men into the profession. CONCLUSIONS: The relationship of
      the distribution of acceptance of male registered nurses found in this study to
      the perceptions of acceptance by male registered nurses is unclear and requires
      further investigation.

PMID- 16579332
TI  - [Continuing care of patients with cardiovascular risk in general practice:
      patients with hypertension and their care].
AB  - INTRODUCTION: Hypertension is an independent cardiovascular risk factor,
      therefore continuing care of patients with hypertension is an important task in
      cardiovascular prevention. AIM: This study was aimed to investigate continuing
      care of hypertension in general practices. Method of the study was a
      questionnaire survey, and 830 adult patients were involved. Forms contained
      information about duration of continuing care, associated risk factors, therapy,
      damages of target organs, and blood pressure values attained. Blood pressure
      measurement and hypertension grading were performed by the recommendation of the
      Hungarian Hypertension Society. RESULTS: Ratios of men and women participated in
      the study were 39.8% and 60.2%, respectively. Duration of hypertension care was
      10.7 +/- 8.3 year. The care was initiated because of moderate and serious
      hypertension in 51.4% and 32.7%, respectively. Frequencies of cardiovascular,
      cerebrovascular and peripheral vascular problems were parallelly increased with
      severity of hypertension. Frequency of all types of antihypertensive drugs used
      were also increased with the hypertension grades. The most frequently used drugs
      were ACE-inhibitors. The target blood pressure of 140/90 Hgmm was reached in
      46.4%, and according to blood pressure measured during the last year of
      continuing care, patients had mild hypertension in 41.5%, moderate in 7.6%, and
      serious one in 0.9%. Effectiveness of the hypertension care, based on decrease in
      blood pressure, was associated with severity of hypertension at the time of its
      diagnosis, the patients' age, but not with their gender. CONCLUSION: Summarizing,
      our results prove that there is a need for intensification of early detection,
      treatment and continuing care of hypertension.

PMID- 16579333
TI  - [Anemia and iron metabolism in patients with type-2 diabetes mellitus].
AB  - INTRODUCTION: Nowadays the iron status in chronic illnesses can be judged by non
      invasive methods, too. The soluble transferrin receptor, that is also measurable
      in most laboratories, means a leap forward among the new markers. AIMS: The
      authors examined the prevalence of anemia and the iron status of type-2 diabetic
      patients with markers of the iron metabolism. They studied the clinical
      applicability of these laboratory procedures. METHODS: Concentration of iron,
      transferrin, ferritin and soluble transferrin receptor levels of healthy and
      diabetic patients were compared with a Mann-Whitney U-test. They examined the
      incidence and the type of anemia, the cause of the elevation in soluble
      transferrin receptor levels, and the effect of inflammation and nephropathy on
      the iron status. Relationship of the transferrin saturation, the concentration of
      ferritin and soluble transferrin receptor levels were depicted by graphic
      representations. RESULTS: The authors have found difference between the
      transferrin levels of women and men in contrast to the literature (z = 3.56; p <
      0.05). The reference intervals of the ferritin levels of the control and patient
      groups also showed a significant difference between women and men (z = 7.59; z =
      5.69; p < 0.05). 7% of the patients have suffered from anemia. 23% of the patient
      group had nephropathy, 10% of this subgroup was anemic, and further 8% of this
      subgroup had iron distribution disorder. 6% of the patients had elevated soluble
      transferrin receptor levels. Anemia or iron metabolism alteration was found only
      in 14% of the cases with elevated C-reactive protein levels. CONCLUSIONS:
      According to these findings ferritin reference levels of healthy people can not
      be used in diabetes mellitus similarly to other chronic illnesses. It seems that
      anemia is not frequent in diabetes mellitus. There is no connection between
      nephropathy and anemia, and not all of the inflammatory conditions are
      accompanied with iron metabolism disturbance. The soluble transferrin receptor
      can be interpreted only together with the other markers. In the opinion of the
      authors, the iron status of an individual can be judged with the collective use
      of all markers in chronic diseases, too.

PMID- 16579335
TI  - [The role of transcranial Doppler sonography in the diagnosis of brain death (a
      practical review)].
AB  - The role of transcranial Doppler sonography in diagnosis of brain death (a
      practical review). The authors summarize the most important technical and
      practical knowledge regarding transcranial Doppler sonography. The characteristic
      Doppler signs of the cessation of cerebral blood flow are demonstrated, such as:
      oscillating flow, systolic spikes and zero-flow. The relatively high sensitivity
      (93.3%) of the repeated transcranial Doppler measurements in brain death
      diagnosis is highlighted.

PMID- 16579334
TI  - [Prevalence of musculoskeletal symptoms in adulthood and adolescence (survey
      conducted in the Southern Transdanubian region in a representative sample of
      10.000 people].
AB  - The time period between 2000-2010 has been declared the "bone and joint decade"
      by the World Health Organisation. Throughout this time the international
      scientific interest focuses mainly on the muskuloskeletal diseases: epidemiology,
      preventive and therapeutic measures. OBJECTIVE: Joining this international effort
      authors aim was to define the prevalence of the musculoskeletal symptoms and the
      general musculoskeletal state of health of a representative sample in the
      hungarian population. METHOD: Obtaining data from the Central Office of
      Statistics, a sample of 10 thousand people living in the South Transdanubian
      Region aged between 14-65 years was selected. The sample was representative
      concerning age, employment and municipal structure. A survey was performed by
      asking the people to fill out a questionnaire made by the authors, which
      consisted of questions focusing on musculoskeletal symptoms, and the Short Form
      36 questionnaire. RESULTS: Based on questionnaire data, approximate prevalence
      values of the different musculoskeletal complaints were obtained. Thus, the
      prevalence of low back pain was 44.1%, hip pain occurred in 22.2%, knee pain in
      30.3%, and ankle pain in 9.7% in the observed population. CONCLUSION: Compared
      with the international data, authors conclude that the prevalence of the
      musculoskeletal symptoms: low back pain, hip and knee pain is superior in the
      observed sample. Based on the results of the Short Form-36 questionnaire it seems
      that in the majority of the examined parameters the state of health is worse in
      the Southern Transdanubian population compared to the Western European and the
      North American Populations.

PMID- 16579337
TI  - [Ninety years ago was founded the barrack hospital (the military hospital of the
      I. world war) in Nyiregyhaza].

PMID- 16579336
TI  - [Current concepts in the genetics of hereditary and sporadic colorectal cancer
      and the role of genetics in patient management. Hereditary colorectal cancers].
AB  - Colorectal cancer (CRC) is the second leading cause of mortality of malignant
      diseases in Hungary and according to the incidence and prevalence of CRC Hungary
      is second among European countries. Hence, it is of outstanding interest to know
      the current concepts on pathogenesis and genetical background of CRC, as well as
      incorporate this knowledge in the everyday practice. In the first part of the
      review authors address the genetic background of hereditary colorectal cancer
      syndromes. In fact, a positive family history may be found in 20-30% and
      genetically defined trait (e.g. familial adenomatous polyposis (FAP), hereditary
      nonpolyposis colorectal cancer (HNPCC) and Peutz-Jeghers-syndrome (PJS)) is
      responsible for 3-5% of all colon cancers. Germline mutations of tumor suppressor
      gene, APC (5q21) are found in 70-90% of the cases. Until now more than 300
      mutations were identified. Though a typical mutation was not found, the location
      of the mutation is associated to the clinical phenotype and prognosis. Of note,
      beside APC mutations, biallelic mutations of the MYH gene may be found in a
      subset of individuals with FAP. The diagnosis of HNPCC is based on family history
      and the presence of Amsterdam I-Il or Bethesda criteria. The genetic background
      and clinical phenotype of the syndrome is heterogeneous. Mutations of different
      mismatch repair genes (mainly hMLH1 or hMSH2) may be identified in most cases.
      Genetic testing is advised in first degree relatives of FAP patients, if genetic
      testing is not available colonoscopic surveillance should be done starting at the
      age of 10-12 years. Due to the high number of mutation genetic testing is
      difficult in HNPCC families and colonoscopic screening should be advised to
      affected families.

PMID- 16579338
TI  - [Contribution to the portrait of a faithful physician: Imre Magyar, the
      belletrist physician]].

PMID- 16579339
TI  - ECG of the month. Long P-R interval, retrograde P waves, or atrioventricular
      dissociation? Sinus rhythm with sinus arrhythmia.

PMID- 16579340
TI  - Radiology case of the month. Unusual pelvic mass and abdominal / pelvic pain in a
      15-year-old girl. Imperforate hymen with hematocolpos.

PMID- 16579341
TI  - Pathology case of the month. A man with an abdominal wall lesion. Squamous cell
      carcinoma of the urinary bladder associated with exstrophy of the urinary
      bladder.

PMID- 16579342
TI  - An updated review on ischemic stroke.

PMID- 16579343
TI  - Clinical uses of electrocardiographic lead aVR.
AB  - Electrocardiographic lead aVR, an augmented unipolar limb lead, for the most part
      has been ignored in clinical practice. Lead aVR, however, can be useful in
      diagnosing and determining prognosis in a variety of cardiovascular conditions,
      including myocardial infarction, myocardial ischemia, conduction disturbances,
      supraventricular arrhythmias, acute pericarditis, and pulmonary emboli. Careful
      attention to lead aVR, as well as the other 11 leads of the standard
      electrocardiogram, can be rewarding to the physicians caring for patients with
      cardiovascular disease.

PMID- 16579344
TI  - Biopsy findings in PET/CT-positive lung lesions in a community hospital.
AB  - An investigation was undertaken to determine the significance of
      fluorodeoxyglucose (FDG) uptake in lung abnormalities on positron emission
      tomography / computed tomography (PET/CT) in our practice. Factors such as lesion
      size, standard uptake value (SUV), multiplicity of pulmonary parenchymal
      abnormalities, and the presence of FDG uptake in mediastinal and hilar lymph
      nodes were analyzed as possible predictors of benign or malignant etiology.
      METHODS: PET/CT reports from 5/20/02 to 6/1/03 were reviewed, and 263 patients
      with significant FDG uptake (maximum SUV > or = 2.5) in pulmonary abnormalities
      were identified. This list of patients was cross referenced with pathology
      reports. Seventy-three of the 263 patients had biopsy results available for the
      corresponding PET/CT abnormality. These patients composed the study population.
      These PET/CT images, reports, and pathology reports were reviewed to determine
      the maximum SUV and size of the pulmonary lesion; the presence of additional
      pulmonary abnormalities and the presence of FDG uptake in mediastinal and hilar
      lymph nodes were recorded. RESULTS: Eighteen of 73 patients had benign diagnoses
      at biopsy (25%), and 55 of 73 patients had pulmonary malignancies (75%). Size of
      the lesion and SUV were not useful in differentiating the benign from malignant
      groups. Multiplicity suggested a benign etiology, but was not statistically
      significant (p = .065). The presence of FDG uptake in mediastinal or hilar lymph
      nodes was a significant predictor of a malignant etiology for the pulmonary
      lesion (p = .024). CONCLUSION: FDG uptake (SUV max > or = 2.5) in a pulmonary
      abnormality indicated a malignant etiology in 75% of patients. The presence of
      FDG uptake in mediastinal or hilar lymph nodes increases the likelihood to 81%
      that a "hot" pulmonary nodule or mass is malignant.

PMID- 16579345
TI  - Pediatric Hodgkin's and non-Hodgkin's lymphomas: a retrospective analysis at the
      Children's Hospital of New Orleans.
AB  - Lymphomas constitute 10-12% of childhood cancers and are the third most common
      childhood malignancy. A retrospective analysis of thirty-six patients from the
      tumor registry of Children's Hospital of New Orleans was conducted during the
      period from 1995-2000. Patients were divided based on patient and tumor
      characteristics with recurrence and survival data compared to the Surveillance,
      Epidemiology and End Results (SEER) data of the National Cancer Institute. There
      were 18 patients (51%) with Non-Hodgkin's Lymphoma (NHL) and 17 (49%) with
      Hodgkin's disease (HD). Our sample had a similar distribution compared to the
      national population cohort except for different gender distribution in our HD
      patients. Also, most of our patients (63%) presented with advanced disease
      (Stages III and IV). Seventeen percent had recurrence of disease and 80% achieved
      remission, of which two patients developed secondary leukemia. Overall mortality
      was 17%. The survival in patients with HD was 94% which is comparable if not
      slightly superior to the national data. In patients with NHL, survival was 72%
      which was marginally lower than the national results (80%), most likely due to
      more advanced disease. Increased awareness in the pediatric community of the
      signs and symptoms of childhood lymphoma should result in earlier diagnosis and
      improved survival.

PMID- 16579346
TI  - The epidemiology, toxidromic classification, general management, and prevention
      of mushroom poisoning in the United States.
AB  - Since the 1950s, reports of severe and fatal mushroom poisonings have increased
      worldwide. Clinicians must consider mushroom poisoning in the evaluation of all
      patients who may be intoxicated by natural substances. Because information on
      natural exposures is often incorrect or insufficient, a new syndromic
      classification of mushroom poisoning is proposed to guide clinicians in making
      earlier diagnoses, especially in cases where only advanced critical care,
      including kidney or liver transplantation, may be life saving.

PMID- 16579348
TI  - Freud in our midst.

PMID- 16579349
TI  - Biology of the mind.

PMID- 16579347
TI  - Brown bowel syndrome: case report and review.
AB  - Brown bowel syndrome is characterized by deposits of lipofuscin in the tunica
      muscularis of the small intestine. Its etiology is associated with chronic
      malabsorption resulting in a deficiency of vitamin E. This hypovitaminosis is
      believed to cause a mitochondrial myopathy secondary to loss of the antioxidant
      properties of vitamin E, which further worsens the malabsorption and leads to
      atonic, dilated segments of bowel. Current treatment options involve nutritional
      supplementation, surgical resection of the affected segments, and intestinal
      transplantation.

PMID- 16579350
TI  - The therapist as scientist.

PMID- 16579351
TI  - Perchance to...eat?

PMID- 16579352
TI  - Spreading the word.

PMID- 16579353
TI  - Take your seat.

PMID- 16579354
TI  - Strategy diagnosis.

PMID- 16579355
TI  - Under the influence. How does patient satisfaction affect survey response and
      completion rates?

PMID- 16579356
TI  - Balancing act. Choosing between proprietary and nonproprietary events requires
      careful consideration.

PMID- 16579357
TI  - Spring ahead. Start early in transitioning to a new advertising agency.

PMID- 16579358
TI  - Listen to the web. Widespread usage of voice-enabled web sites is a not-so
      distant possibility.

PMID- 16579359
TI  - Rules of attraction.

PMID- 16579360
TI  - Role models wanted.

PMID- 16579361
TI  - Focus on the customer.

PMID- 16579362
TI  - Establish relationships.

PMID- 16579363
TI  - Look beyond research.

PMID- 16579364
TI  - Form a link.

PMID- 16579365
TI  - Stay on schedule.

PMID- 16579366
TI  - Marketing feedback.

PMID- 16579367
TI  - Know your marketplace.

PMID- 16579368
TI  - Circular healthcare. Is a crisis needed to stop healthcare from continuing in its
      current pattern?

PMID- 16579369
TI  - Light field compression using disparity-compensated lifting and shape adaptation.
AB  - We propose disparity-compensated lifting for wavelet compression of light fields.
      With this approach, we obtain the benefits of wavelet coding, such as scalability
      in all dimensions, as well as superior compression performance. Additionally, the
      proposed approach solves the irreversibility limitations of previous light field
      wavelet coding approaches, using the lifting structure. Our scheme incorporates
      disparity compensation into the lifting structure for the transform across the
      views in the light field data set. Another transform is performed to exploit the
      coherence among neighboring pixels, followed by a modified SPIHT coder and rate
      distortion optimized bitstream assembly. A view-sequencing algorithm is developed
      to organize the views for encoding. For light fields of an object, we propose to
      use shape adaptation to improve the compression efficiency and visual quality of
      the images. The necessary shape information is efficiently coded based on
      prediction from the existing geometry model. Experimental results show that the
      proposed scheme exhibits superior compression performance over existing light
      field compression techniques.

PMID- 16579370
TI  - A syntax-preserving error resilience tool for JPEG 2000 based on error correcting
      arithmetic coding.
AB  - JPEG 2000 is the novel ISO standard for image and video coding. Besides its
      improved coding efficiency, it also provides a few error resilience tools in
      order to limit the effect of errors in the codestream, which can occur when the
      compressed image or video data are transmitted over an error-prone channel, as
      typically occurs in wireless communication scenarios. However, for very harsh
      channels, these tools often do not provide an adequate degree of error
      protection. In this paper, we propose a novel error-resilience tool for JPEG
      2000, based on the concept of ternary arithmetic coders employing a forbidden
      symbol. Such coders introduce a controlled degree of redundancy during the
      encoding process, which can be exploited at the decoder side in order to detect
      and correct errors. We propose a maximum likelihood and a maximum a posteriori
      context-based decoder, specifically tailored to the JPEG 2000 arithmetic coder,
      which are able to carry out both hard and soft decoding of a corrupted code
      stream. The proposed decoder extends the JPEG 2000 capabilities in error-prone
      scenarios, without violating the standard syntax. Extensive simulations on video
      sequences show that the proposed decoders largely outperform the standard in
      terms of PSNR and visual quality.

PMID- 16579371
TI  - Reducing video-quality fluctuations for streaming scalable video using unequal
      error protection, retransmission, and interleaving.
AB  - Forward error correction based multiple description (MD-FEC) transcoding for
      transmitting embedded bitstream over the packet erasure networks has been
      extensively studied in the past. In the existing work, a single embedded source
      bitstream, e.g., the bitstream of a group of pictures (GOP) encoded using three
      dimensional set partitioning in hierarchical trees is optimally protected unequal
      error protection (UEP) in the rate-distortion sense. However, most of the
      previous work on transmitting embedded video using MD-FEC assumed that one GOP is
      transmitted only once, and did not consider the chance of retransmission. This
      may lead to noticeable video quality variations due to varying channel
      conditions. In this paper, a novel window-based packetization scheme is proposed,
      which combats bursty packet loss by combining the following three techniques:
      UEP, retransmission, and GOP-level interleaving. In particular, two
      retransmission mechanisms, namely segment-wise retransmission and byte-wise
      retransmission, are proposed based on different types of receiver feedback.
      Moreover, two levels of rate allocations are introduced: intra-GOP rate
      allocation minimizes the distortion of individual GOP; while inter-GOP rate
      allocation intends to reduce video quality fluctuations by adaptively allocating
      bandwidth according to video signal characteristics and client buffer status. In
      this way, more consistent video quality can be achieved under various packet loss
      probabilities, as demonstrated by our experimental results.

PMID- 16579372
TI  - A cross-layer diversity technique for multicarrier OFDM multimedia networks.
AB  - Diversity can be used to combat multipath fading and improve the performance of
      wireless multimedia communication systems. In this work, by considering
      transmission of an embedded bitstream over an orthogonal frequency division
      multiplexing (OFDM) system in a slowly varying Rayleigh faded environment, we
      develop a cross-layer diversity technique which takes advantage of both multiple
      description coding and frequency diversity techniques. More specifically,
      assuming a frequency-selective channel, we study the packet loss behavior of an
      OFDM system and construct multiple independent descriptions using an FEC-based
      strategy. We provide some analysis of this cross-layer approach and demonstrate
      its superior performance using the set partitioning in hierarchical trees image
      coder.

PMID- 16579373
TI  - An analysis of the efficiency of different SNR-scalable strategies for video
      coders.
AB  - In this paper, we analyze the efficiency of three signal-to-noise scalable
      strategies for video coders using single-loop motion-compensated prediction
      (MCP). In our analysis, we assume the video sequences have uniform and constant
      translational motion and we model MCP as a stochastic filter. We also assume an
      exponential model for the distortion-rate function of the intraframe coding. The
      analysis is divided into two parts: the steady-state analysis and the transient
      analysis. In the first part, only the steady-state response of the coders is
      taken into account, and, thus, this analysis allows us to asses approximately the
      efficiency of coders with long input sequences. The transitory analysis considers
      both the transient and the steady-state responses of the coders, which makes it
      appropriate to analyze coders using periodic intraframes or with short input
      sequences. To validate our analysis, theoretical results have been compared to
      results from encodings of real video sequences using the scalable adaptive motion
      compensated wavelet video coder. We show that our theoretical analysis
      effectively describes qualitatively the main trends of every video coding
      strategy.

PMID- 16579374
TI  - Maximum-likelihood estimation of circle parameters via convolution.
AB  - The accurate fitting of a circle to noisy measurements of circumferential points
      is a much studied problem in the literature. In this paper, we present an
      interpretation of the maximum-likelihood estimator (MLE) and the Delogne-Kasa
      estimator (DKE) for circle-center and radius estimation in terms of convolution
      on an image which is ideal in a certain sense. We use our convolution-based MLE
      approach to find good estimates for the parameters of a circle in digital images.
      In digital images, it is then possible to treat these estimates as preliminary
      estimates into various other numerical techniques which further refine them to
      achieve subpixel accuracy. We also investigate the relationship between the
      convolution of an ideal image with a "phase-coded kernel" (PCK) and the MLE. This
      is related to the "phase-coded annulus" which was introduced by Atherton and
      Kerbyson who proposed it as one of a number of new convolution kernels for
      estimating circle center and radius. We show that the PCK is an approximate MLE
      (AMLE). We compare our AMLE method to the MLE and the DKE as well as the Cramer
      Rao Lower Bound in ideal images and in both real and synthetic digital images.

PMID- 16579375
TI  - Correcting curvature-density effects in the Hamilton-Jacobi skeleton.
AB  - The Hamilton-Jacobi approach has proven to be a powerful and elegant method for
      extracting the skeleton of two-dimensional (2-D) shapes. The approach is based on
      the observation that the normalized flux associated with the inward evolution of
      the object boundary at nonskeletal points tends to zero as the size of the
      integration area tends to zero, while the flux is negative at the locations of
      skeletal points. Nonetheless, the error in calculating the flux on the image
      lattice is both limited by the pixel resolution and also proportional to the
      curvature of the boundary evolution front and, hence, unbounded near endpoints.
      This makes the exact location of endpoints difficult and renders the performance
      of the skeleton extraction algorithm dependent on a threshold parameter. This
      problem can be overcome by using interpolation techniques to calculate the flux
      with subpixel precision. However, here, we develop a method for 2-D skeleton
      extraction that circumvents the problem by eliminating the curvature contribution
      to the error. This is done by taking into account variations of density due to
      boundary curvature. This yields a skeletonization algorithm that gives both
      better localization and less susceptibility to boundary noise and parameter
      choice than the Hamilton-Jacobi method.

PMID- 16579376
TI  - Multiple contour extraction from graylevel images using an artificial neural
      network.
AB  - For active contour modeling (ACM), we propose a novel self-organizing map (SOM)
      based approach, called the batch-SOM (BSOM), that attempts to integrate the
      advantages of SOM- and snake-based ACMs in order to extract the desired contours
      from images. We employ feature points, in the form of an edge-map (as obtained
      from a standard edge-detection operation), to guide the contour (as in the case
      of SOM-based ACMs) along with the gradient and intensity variations in a local
      region to ensure that the contour does not "leak" into the object boundary in
      case of faulty feature points (weak or broken edges). In contrast with the snake
      based ACMs, however, we do not use an explicit energy functional (based on
      gradient or intensity) for controlling the contour movement. We extend the BSOM
      to handle extraction of contours of multiple objects, by splitting a single
      contour into as many subcontours as the objects in the image. The BSOM and its
      extended version are tested on synthetic binary and gray-level images with both
      single and multiple objects. We also demonstrate the efficacy of the BSOM on
      images of objects having both convex and nonconvex boundaries. The results
      demonstrate the superiority of the BSOM over others. Finally, we analyze the
      limitations of the BSOM.

PMID- 16579377
TI  - A nonlinear image contrast sharpening approach based on Munsell's scale.
AB  - Contrast is a measure of the variation in intensity or gray value in a specified
      region of an image. The region can be most or all of the image, giving rise to a
      global concept of contrast. The region might, on the other hand, be a small
      window in which case the concept of contrast is a locally defined expression. In
      this work, we introduce a nonlinear local contrast enhancement method. This
      method utilizes the Munsell value scale which is based upon human visual
      perception. Use of the Munsell value scale allows for the partitioning of the
      gray scale into ten discrete subintervals. Subsequent local processing occurs
      within each of these subintervals. Inside each subinterval, this method
      constructs a contrast enhancement function that is a smooth approximation to the
      threshold step function and which maps a given subinterval into itself. This
      function then thresholds the gray values in a subinterval in a smooth manner
      about a locally computed quantity called the mean edge gray value. By enhancing
      the contrast in this way, the original shades of gray are preserved. That is, the
      groupings of the gray values by subinterval are preserved. As a result, no gray
      value distortion is introduced into the image.

PMID- 16579378
TI  - The fuzzy transformation and its applications in image processing.
AB  - The spatial and rank (SR) orderings of samples play a critical role in most
      signal processing algorithms. The recently introduced fuzzy ordering theory
      generalizes traditional, or crisp, SR ordering concepts and defines the fuzzy
      (spatial) samples, fuzzy order statistics, fuzzy spatial indexes, and fuzzy
      ranks. Here, we introduce a more general concept, the fuzzy transformation (FZT),
      which refers to the mapping of the crisp samples, order statistics, and SR
      ordering indexes to their fuzzy counterparts. We establish the element invariant
      and order invariant properties of the FZT. These properties indicate that fuzzy
      spatial samples and fuzzy order statistics constitute the same set and, under
      commonly satisfied membership function conditions, the sample rank order is
      preserved by the FZT. The FZT also possesses clustering and symmetry properties,
      which are established through analysis of the distributions and expectations of
      fuzzy samples and fuzzy order statistics. These properties indicate that the FZT
      incorporates sample diversity into the ordering operation, which can be utilized
      in the generalization of conventional filters. Here, we establish the fuzzy
      weighted median (FWM), fuzzy lower-upper-middle (FLUM), and fuzzy identity
      filters as generalizations of their crisp counterparts. The advantage of the
      fuzzy generalizations is illustrated in the applications of DCT coded image
      deblocking, impulse removal, and noisy image sharpening.

PMID- 16579379
TI  - A hybrid neuro-fuzzy filter for edge preserving restoration of images corrupted
      by impulse noise.
AB  - A new operator for restoring digital images corrupted by impulse noise is
      presented. The proposed operator is a hybrid filter obtained by appropriately
      combining a median filter, an edge detector, and a neuro-fuzzy network. The
      internal parameters of the neuro-fuzzy network are adaptively optimized by
      training. The training is easily accomplished by using simple artificial images
      that can be generated in a computer. The most distinctive feature of the proposed
      operator over most other operators is that it offers excellent line, edge,
      detail, and texture preservation performance while, at the same time, effectively
      removing noise from the input image. Extensive simulation experiments show that
      the proposed operator may be used for efficient restoration of digital images
      corrupted by impulse noise without distorting the useful information in the
      image.

PMID- 16579380
TI  - Bayesian wavelet-based image deconvolution: a GEM algorithm exploiting a class of
      heavy-tailed priors.
AB  - Image deconvolution is formulated in the wavelet domain under the Bayesian
      framework. The well-known sparsity of the wavelet coefficients of real-world
      images is modeled by heavy-tailed priors belonging to the Gaussian scale mixture
      (GSM) class; i.e., priors given by a linear (finite of infinite) combination of
      Gaussian densities. This class includes, among others, the generalized Gaussian,
      the Jeffreys, and the Gaussian mixture priors. Necessary and sufficient
      conditions are stated under which the prior induced by a thresholding/shrinking
      denoising rule is a GSM. This result is then used to show that the prior induced
      by the "nonnegative garrote" thresholding/shrinking rule, herein termed the
      garrote prior, is a GSM. To compute the maximum a posteriori estimate, we propose
      a new generalized expectation maximization (GEM) algorithm, where the missing
      variables are the scale factors of the GSM densities. The maximization step of
      the underlying expectation maximization algorithm is replaced with a linear
      stationary second-order iterative method. The result is a GEM algorithm of O(N
      log N) computational complexity. In a series of benchmark tests, the proposed
      approach outperforms or performs similarly to state-of-the art methods, demanding
      comparable (in some cases, much less) computational complexity.

PMID- 16579381
TI  - Precise segmentation of multimodal images.
AB  - We propose new techniques for unsupervised segmentation of multimodal grayscale
      images such that each region-of-interest relates to a single dominant mode of the
      empirical marginal probability distribution of grey levels. We follow the most
      conventional approaches in that initial images and desired maps of regions are
      described by a joint Markov-Gibbs random field (MGRF) model of independent image
      signals and interdependent region labels. However, our focus is on more accurate
      model identification. To better specify region borders, each empirical
      distribution of image signals is precisely approximated by a linear combination
      of Gaussians (LCG) with positive and negative components. We modify an
      expectation-maximization (EM) algorithm to deal with the LCGs and also propose a
      novel EM-based sequential technique to get a close initial LCG approximation with
      which the modified EM algorithm should start. The proposed technique identifies
      individual LCG models in a mixed empirical distribution, including the number of
      positive and negative Gaussians. Initial segmentation based on the LCG models is
      then iteratively refined by using the MGRF with analytically estimated
      potentials. The convergence of the overall segmentation algorithm at each stage
      is discussed. Experiments show that the developed techniques segment different
      types of complex multimodal medical images more accurately than other known
      algorithms.

PMID- 16579382
TI  - Seamless image stitching by minimizing false edges.
AB  - Various applications such as mosaicing and object insertion require stitching of
      image parts. The stitching quality is measured visually by the similarity of the
      stitched image to each of the input images, and by the visibility of the seam
      between the stitched images. In order to define and get the best possible
      stitching, we introduce several formal cost functions for the evaluation of the
      stitching quality. In these cost functions the similarity to the input images and
      the visibility of the seam are defined in the gradient domain, minimizing the
      disturbing edges along the seam. A good image stitching will optimize these cost
      functions, overcoming both photometric inconsistencies and geometric
      misalignments between the stitched images. We study the cost functions and
      compare their performance for different scenarios both theoretically and
      practically. Our approach is demonstrated in various applications including
      generation of panoramic images, object blending and removal of compression
      artifacts. Comparisons with existing methods show the benefits of optimizing the
      measures in the gradient domain.

PMID- 16579383
TI  - Optimal temporal interpolation filter for motion-compensated frame rate up
      conversion.
AB  - Frame rate up conversion (FRUC) methods that employ motion have been proven to
      provide better image quality compared to nonmotion-based methods. While motion
      based methods improve the quality of interpolation, artifacts are introduced in
      the presence of incorrect motion vectors. In this paper, we study the design
      problem of optimal temporal interpolation filter for motion-compensated FRUC (MC
      FRUC). The optimal filter is obtained by minimizing the prediction error variance
      between the original frame and the interpolated frame. In FRUC applications, the
      original frame that is skipped is not available at the decoder, so models for the
      power spectral density of the original signal and prediction error are used to
      formulate the problem. The closed-form solution for the filter is obtained by
      Lagrange multipliers and statistical motion vector error modeling. The effect of
      motion vector errors on resulting optimal filters and prediction error is
      analyzed. The performance of the optimal filter is compared to nonadaptive
      temporal averaging filters by using two different motion vector reliability
      measures. The results confirm that to improve the quality of temporal
      interpolation in MC, the interpolation filter should be designed based on the
      reliability of motion vectors and the statistics of the MC prediction error.

PMID- 16579384
TI  - Asymptotically optimal blind estimation of multichannel images.
AB  - Optimal estimation of a two-dimensional (2-D) multichannel signal ideally
      decorrelates the data in both channel and space and weights the resulting
      coefficients according to their SNR. Many scenarios exist where the required
      second-order signal and noise statistics are not known in which the decorrelation
      is difficult or expensive to calculate. An asymptotically optimal estimation
      scheme proposed here uses a 2-D discrete wavelet transform to approximately
      decorrelate the signal in space and the discrete Fourier transform to decorrelate
      between channels. The coefficient weighting is replaced with a wavelet-domain
      thresholding operation to result in an efficient estimation scheme for both
      stationary and nonstationary signals. In contrast to optimal estimation, this new
      scheme does not require second-order signal statistics, making it well suited to
      many applications. In addition to providing vastly improved visual quality, the
      new estimator typically yields signal-to-noise ratio gains 12 dB or higher for
      hyperspectral imagery and functional magnetic resonance images.

PMID- 16579385
TI  - Motion measurement errors and autofocus in bistatic SAR.
AB  - This paper discusses the effect of motion measurement errors (MMEs) on measured
      bistatic synthetic aperture radar (SAR) phase history data that has been motion
      compensated to the scene origin. We characterize the effect of low-frequency MMEs
      on bistatic SAR images, and, based on this characterization, we derive limits on
      the allowable MMEs to be used as system specifications. Finally, we demonstrate
      that proper orientation of a bistatic SAR image during the image formation
      process allows application of monostatic SAR autofocus algorithms in
      postprocessing to mitigate image defocus.

PMID- 16579386
TI  - Relevance feedback for CBIR: a new approach based on probabilistic feature
      weighting with positive and negative examples.
AB  - In content-based image retrieval, understanding the user's needs is a challenging
      task that requires integrating him in the process of retrieval. Relevance
      feedback (RF) has proven to be an effective tool for taking the user's judgement
      into account. In this paper, we present a new RF framework based on a feature
      selection algorithm that nicely combines the advantages of a probabilistic
      formulation with those of using both the positive example (PE) and the negative
      example (NE). Through interaction with the user, our algorithm learns the
      importance he assigns to image features, and then applies the results obtained to
      define similarity measures that correspond better to his judgement. The use of
      the NE allows images undesired by the user to be discarded, thereby improving
      retrieval accuracy. As for the probabilistic formulation of the problem, it
      presents a multitude of advantages and opens the door to more modeling
      possibilities that achieve a good feature selection. It makes it possible to
      cluster the query data into classes, choose the probability law that best models
      each class, model missing data, and support queries with multiple PE and/or NE
      classes. The basic principle of our algorithm is to assign more importance to
      features with a high likelihood and those which distinguish well between PE
      classes and NE classes. The proposed algorithm was validated separately and in
      image retrieval context, and the experiments show that it performs a good feature
      selection and contributes to improving retrieval effectiveness.

PMID- 16579387
TI  - An RBF-based compression method for image-based relighting.
AB  - In image-based relighting, a pixel is associated with a number of sampled
      radiance values. This paper presents a two-level compression method. In the first
      level, the plenoptic property of a pixel is approximated by a spherical radial
      basis function (SRBF) network. That means that the spherical plenoptic function
      of each pixel is represented by a number of SRBF weights. In the second level, we
      apply a wavelet-based method to compress these SRBF weights. To reduce the visual
      artifact due to quantization noise, we develop a constrained method for
      estimating the SRBF weights. Our proposed approach is superior to JPEG, JPEG2000,
      and MPEG. Compared with the spherical harmonics approach, our approach has a
      lower complexity, while the visual quality is comparable. The real-time rendering
      method for our SRBF representation is also discussed.

PMID- 16579388
TI  - Lossless watermarking for image authentication: a new framework and an
      implementation.
AB  - We present a novel framework for lossless (invertible) authentication
      watermarking, which enables zero-distortion reconstruction of the un-watermarked
      images upon verification. As opposed to earlier lossless authentication methods
      that required reconstruction of the original image prior to validation, the new
      framework allows validation of the watermarked images before recovery of the
      original image. This reduces computational requirements in situations when either
      the verification step fails or the zero-distortion reconstruction is not needed.
      For verified images, integrity of the reconstructed image is ensured by the
      uniqueness of the reconstruction procedure. The framework also enables public(
      key) authentication without granting access to the perfect original and allows
      for efficient tamper localization. Effectiveness of the framework is demonstrated
      by implementing the framework using hierarchical image authentication along with
      lossless generalized-least significant bit data embedding.

PMID- 16579389
TI  - Folklores in medical science.

PMID- 16579390
TI  - Nitric oxide-hemoglobin interactions: role in oxygen uptake and delivery.

PMID- 16579391
TI  - Antinociceptive effect of sucrose ingestion in the human.
AB  - Sucrose ingestion has been shown to alleviate pain and distress in rats, human
      infants as well as adults. Sucrose induced analgesia is related to the reward
      value associated with its sweet taste. The sweet taste of sucrose is a stimulus
      for the activation of endogenous opioid pool. The opioids in turn modulate pain
      perception. It has been demonstrated in a number of animal and human studies that
      sucrose ingestion increases the hypothalamic/CSF opioid levels. This gains
      support from the results obtained from naloxone challenge test, a neuro-endocrine
      method for assessment of endogenous opioid tone. Moreover, the analgesic effects
      of sucrose can be reversed by administration of opioid antagonists such as
      naloxone. On the other hand, long-term sucrose ingestion leads to hyperalgesia in
      rats and it has been hypothesized to result from a complex interaction of sucrose
      with the endogenous opioid system leading to a deficiency of opioids. In the
      present article mechanisms underlying sucrose induced analgesia including the
      interaction of the palatability and reward value of food with the neural
      substrates and its neuro-chemical basis have been reviewed in the light of both
      animal and human studies. In addition, clinical application of the knowledge
      about sucrose and its modulatory effect on the endogenous opioid system has been
      suggested.

PMID- 16579392
TI  - Effect of alpha lipoic acid, melatonin and trans resveratrol on
      intracerebroventricular streptozotocin induced spatial memory deficit in rats.
AB  - In the present study, the effect of antioxidants-alpha lipoic acid, melatonin and
      trans resveratrol were studied against intracerebroventricular streptozotocin
      induced spatial memory deficit. Male Wistar rats were injected with
      intracerebroventricular streptozotocin bilaterally. The rats were treated
      chronically with alpha lipoic acid (200 mg/kg, po), melatonin (20 mg/kg, ip) and
      trans resveratrol (20 mg/kg, ip) for 18 days starting from day 1 of
      streptozotocin injection in separate groups. The spatial memory was evaluated
      using the Morris water maze task. The intracerebroventricular streptozotocin rats
      treated with antioxidants showed significantly less spatial memory deficit both
      in the acquisition and probe trials as compared to the vehicle treated rats. The
      study demonstrated the effectiveness of alpha lipoic acid, melatonin and trans
      resveratrol in preventing spatial memory deficit induced by
      intracerebroventricular streptozotocin and it's potential in age related
      neurodegenerative disorders where oxidative stress is involved such as
      Alzheimer's disease.

PMID- 16579393
TI  - Renal humoral modulation of skeletal muscle tone in mice: implications for 'the
      pulmonary-renal cascade'.
AB  - The pulmonary-renal cascade may regulate the respiration and skeletal muscle
      contractility. To evaluate this working hypothetical model, we conducted
      experiments to ascertain the skeletal muscle tone of the Swiss mice (20-35 g).
      The animals were evaluated for their skeletal muscle tone via several techniques
      i.e. inclined plane test, grip strength test and swim test. Groups of mice (n=6)
      were pre-treated with mefenamic acid (60 mg/kg, i.p), carbenoxolone (100 mg/kg
      i.p) or vehicle only 15 minutes before the treatment with heparin (500 U/kg,
      i.v), urokinase (5500 U/kg, i.v) and erythropoietin (150 U/kg, i.v). Heparin
      potentiated the loss of skeletal muscle tone induced by mefenamic acid and
      carbenoxolone while urokinase & erythropoietin significantly enhanced the
      skeletal muscle tone as evaluated by all or one of the tests. Other groups of
      mice (n=6) were pretreated with mefenamic acid (1 mg i.c.v), carbenoxolone (160
      microg i.c.v) or minoxidil (30 microg i.c.v) and the effects of heparin &
      urokinase and erythropoietin on skeletal muscle tone were evaluated. To study the
      effects of heparin and urokinase on nerve regeneration, two groups of mice
      underwent a sham and sciatic nerve crush procedure. The mice treated with
      urokinase recovered much faster as compared to those treated with heparin or
      saline. These experimental results suggest that gap junction blockers and
      potassium channel openers interact with heparin, urokinase and erythropoietin to
      control the skeletal muscle tone.

PMID- 16579394
TI  - Sleep changes during chronic cold exposure showed that the homeostatic
      requirement of sleep is reduced in the medial preoptic area lesioned rats.
AB  - The effects of chronic exposure to a mildly cold ambient temperature (T(a)) of 18
      degrees C on sleep wakefulness (S-W) and brain temperature (T(br)) were studied
      in the medial preoptic area (mPOA) lesioned male Wistar rats.
      Electroencephalogram (EEG), electrooculogram (EOG) and electromyogram (EMG)
      electrodes were chronically implanted to assess S-W, and a thermocouple above the
      dura to record the T(br). After three recordings (24 h each) of S-W and T(br) at
      24 degrees C, N-methyl D-aspartic acid (NMDA) was intracerebrally injected to
      produce bilateral destruction of neurons in the mPOA. There was decreased sleep
      and increased T(br) even four weeks after the mPOA lesion. T(a) of the
      environmental chamber was then reduced to 18 degrees C, and the S-W and T(br)
      were again recorded for 24 h each on the 1st, 7th, 14th, 21st, and on 28th days
      of continuous exposure to the mild cold T(a). Exposure to the cold produced
      further decrease in sleep and increase in the T(br). However, sleep came back to
      the pre-exposure level by the 14th day. An increase in the duration of sleep
      episodes was responsible for the restoration of sleep during chronic cold
      exposure. The study showed that the requirement of sleep was reset at a lower
      level in the mPOA lesioned rats. The mPOA lesion affected the sleep maintenance
      and sleep initiation, though the latter became evident only during chronic cold
      exposure. The magnitude of the acute changes in T(br) and S-W were less in the
      lesioned rats, as compared to those observed in the normal rats exposed to
      similar cold T(a). On the basis of these observations, it could be proposed that
      the mPOA plays some role in cold induced changes in thermoregulation and sleep
      regulation. The T(br) remained elevated throughout the period of cold exposure.
      Resetting of the T(br), at a higher level may be part of the homeostatic
      readjustment to restore sleep.

PMID- 16579395
TI  - Effect of ascorbic acid, alpha-tocopherol, lecithin and L-ornithine-L-aspartate
      on ethanol induced hypoproteinemia and hyperlipidemia in rats.
AB  - We studied effect of exogenous ascorbic acid, alpha-tocopherol, lecithin and L
      ornithine-L-aspartate on serum lipids and proteins in experimental hepatotoxic
      Wistar rats. Eleven groups (n = 6) of animals were used. Hepatotoxicity was
      induced by administering ethanol (1.6 g/kg/day) for 28 days. Both preventive and
      curative options were studied. Percentage increase in body weight was
      significantly lower in ethanol treated rats. Ethanol significantly (P<0.05)
      increased cholesterol, triglycerides and LDL, and decreased protein, albumin and
      A:G ratio in serum. Ascorbic acid, alpha-tocopherol, lecithin and L-ornithine-L
      aspartate exhibited an ability to counteract the alcohol-induced changes in the
      body weight and biochemical parameters in preventive and therapeutic models in
      varying degree. Antioxidants showed better effect.

PMID- 16579396
TI  - Effect of intracerebroventricular methotrexate on brain amines.
AB  - Intrathecal methotrexate in children with leukemia is known to cause seizures,
      dementia, leukoencephalopathy and cognitive dysfunction. To investigate the role
      of brain amines in cognitive dysfunction, male Wistar rats were given multiple
      intracerebroventricular injections of methotrexate. Our earlier studies in this
      regard revealed disruption of brain monoamines in hippocampus with severe
      cytotoxic effect on CA4 hippocampal neurons. Further extending this study, the
      levels of brain monoamines in frontal cortex, hypothalamus and brainstem were
      estimated by HPLC method and histopathological study of the frontal cortex. The
      concentration of all three-brain amine (norepinephrine, dopamine and serotonin)
      levels was reduced in 2 mg/kg dose of methotrexate in frontal cortex and brain
      stem. Hypothalamus did not show any significant change in brain monoamine levels.
      No structural changes in the frontal cortex neurons were observed. Disruption of
      brain monoamines has been proposed as a cause of brain dysfunction from this
      chemotherapy. The outcome of the study may have therapeutic implications in the
      management of childhood lymphoblastic leukemia.

PMID- 16579397
TI  - Comparison between pre-prandial and post-prandial heart rate variability (HRV).
AB  - After food ingestion, peptides are released in GIT, which cause local
      vasodilatation. Therefore, after meals, redistribution of blood occurs because of
      shifting of large amounts of blood into GIT. In normal individuals, this is well
      compensated and does not lead to post-prandial hypotension. The mechanism of post
      prandial hypotension is well known. We hypothesized that there may be a decrease
      in parasympathetic activity (tone) after meals to compensate for the change in
      blood distribution. We carried out the study to find out the changes in the
      autonomic tone before and after meals (lunch) in normal individuals, using Heart
      Rate Variability (HRV). From the series of RR intervals marked, the time domain
      and frequency domain measures of HRV were obtained using Nevrokard software
      (version 6.4). Continuous ECG was recorded in 15 healthy adult subjects (mean age
      29.06 +/- 6.2; 13 males and 2 females). The ECG was recorded in pre-prandial and
      post-prandial state for a period of five minutes each as follows: (1) just before
      the subjects had lunch, (2) 15 minutes after lunch, (3) 1 hour after lunch, and
      (4) 2 hours after lunch. Time domain and frequency domain measures of HRV were
      compared between pre-prandial state and rest of post-prandial states. The
      autonomic tone parameters did not show a significant change between the pre
      prandial state and the immediate post-prandial state. [Range, i.e., the
      difference between the maximum and minimum RR intervals (406 +/- 161.14 vs.
      416.66 +/- 125), standard-deviation of normal to normal RR interval (56.33 +/-
      22.72 vs. 67.63 +/- 26.50), RMSSD (55.02 +/- 35.85 vs. 63.87 +/- 32.60), NN50
      (42.13 +/- 29.43 vs. 51.86 +/- 29.83), PNN50 (12.67 +/- 10.29 vs. 15.27 +/-
      9.71), HF (49.53 +/- 15.10 vs. 47.07 +/- 16.88), LF (41.41 +/- 13.18 vs. 46.49 +/
      15.99), LF/HF (0.98 +/- 0.53 vs. 1.26 +/- 0.90), total power (148.27 +/- 37.78
      vs. 137.61 +/- 37.10)]. No significant change was seen in the above parameters
      between the pre-prandial state and the later phases of post-prandial state. Since
      there is no significant decrease in the time domain measures and the HF value
      between the pre-prandial and the post-prandial states, we conclude that the
      parasympathetic tone is not altered. The parameters denoting sympathetic tone,
      ie, LF and LF/HF, also do not show a significant change. This indicates that the
      cardiovascular autonomic tone is not affected by ingestion of meals in normal
      individuals. Thus we refute our hypothesis. In conclusion, the HRV parameters do
      not alter significantly after meals in normal individuals.

PMID- 16579398
TI  - Reversible plasma testosterone levels reduction after gentamicin administration
      and freund's adjuvant arthritis in rats.
AB  - The present study was undertaken in order to investigate the influence of
      gentamicin on plasma testosterone levels of healthy and with Freund's adjuvant
      arthritis rats. Gentamicin (40 mg/day for 4 days) induced significant decrease of
      testosterone levels in comparison with the control group (P<0.025).
      Intraperitoneal calcium administration (30 mg/ kg bw) prevented gentamicin effect
      and maintained testosterone levels to that of the control. Decreased testosterone
      levels were also observed in gentamicin received Freund's adjuvant arthritic
      rats, in the acute stage of the inflammatory disease (P<0.025), and in the acute
      stage of Freund's adjuvant arthritis (P<0.001). It is concluded that the
      administration of gentamicin decreases plasma testosterone levels without any
      effect on body and seminal vesicles weight. Calcium loading counteracts
      gentamicin reducing effect on plasma testosterone levels. Freund's adjuvant
      arthritis influences the function of body and seminal vesicles as it was shown by
      the reduction of testosterone levels, body and seminal vesicles weight during the
      acute phase of the inflammatory disease. In any case the effect was reversible.

PMID- 16579399
TI  - Role of emotionality on inter and intrastrain variations in imipramine response.
      a comparative study in Balb/c and Swiss mice.
AB  - Association between emotionality and effect of imipramine on immobility time in
      forced swimming test was investigated in Swiss and Balb/c mice. Mice of both the
      strains were segregated into normal emotional (mean +/- 1SD), low emotional (>
      mean + 1SD) and high emotional (< mean - 1SD) based on their performance with
      respect to each indices of emotionality in novel arena and elevated plus maze.
      Baseline immobility and effect of imipramine (20 mg/kg, po) on immobility time
      was evaluated in these emotionally different groups of mice using forced swimming
      test model. Baseline immobility time of low emotional mice was found to be
      significantly less (P<0.01) and that of high emotional mice was found to be
      significantly more (P<0.01) when compared to normal emotional mice of both the
      strains. Immobility time after imipramine administration was found to be
      significantly less (P<0.05) with low emotional mice and significantly more
      (P<0.01) with high emotional mice when compared to normal emotional mice of both
      the strains.

PMID- 16579401
TI  - Effect of Sahaj Yoga on depressive disorders.
AB  - Sahaj Yoga is a meditative technique that has been found to have beneficial
      effects in some psycho-somatic illnesses. The study was carried out on 30 cases
      (19 Males, 11 females, age 18-45 years) of major depression diagnosed on the
      basis of DSM IV criteria. The patients were then randomly divided into two
      groups: Group 1: (10 Males & 5 Females) Patients who were practising Sahaj Yoga
      and also received conventional anti-depressants. Group 2: (9 Males & 6 Females)
      Patients who were only receiving conventional anti-depressants. Training in Sahaj
      yoga was conducted under the supervision of a trained Sahaj Yogi for 8 weeks. At
      start of the study, all the patients were subjected to Hamilton Rating Scale for
      Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A). Above scales
      were again assessed after two months of treatment. There was significant
      improvement in HAM-D as well as HAM-A scores in both Group 1 and Group 2 patients
      (P<0.001). However, percentage improvement in HAM-D scores and HAM-A scores in
      patients receiving Sahaj Yoga was significantly higher than in Group 2 patients.
      The number of patients who went into remission after two months of intervention
      were also significantly higher in Group 1 patients (P=0.02). The present study
      demonstrates that Sahaj Yoga has got a potential role as a component in the
      management of depressive disorders.

PMID- 16579400
TI  - Correlation between body mass index and blood pressure indices, handgrip strength
      and handgrip endurance in underweight, normal weight and overweight adolescents.
AB  - In the present study, we investigated the correlation between body mass index
      (BMI), blood pressure (BP) indices and indices of physical fitness in apparently
      healthy subjects aged 14-18 years. We obtained data from 145 (105 males and 40
      females) and assessed the correlation between BMI, and heart rate, systolic
      pressure (SP), diastolic pressure (DP), pulse pressure (PP), mean arterial
      pressure (MP), rate-pressure product, endurance in the 40 mm Hg test, handgrip
      strength (HGS), and handgrip endurance. Subjects with BMI <18.5 kg/m2, 18.5-25
      kg/m2 and >25 kg/m2 were classed as underweight (65 males and 9 females), normal
      weight (27 males and 20 females), and overweight (13 males and 11 females)
      respectively. In view of gender differences in autonomic regulation, data of male
      and female subjects were analyzed separately. We used analysis of variance to
      compare differences between the three groups. Correlation between BMI and other
      indices was tested using Pearson's correlation coefficient. A P value <0.05 was
      considered statistically significant Both SP and DP were highest in overweight
      and least in underweight male subjects (P<0.05 for both), whereas in females,
      differences in DP alone were statistically significant (P<0.05). In underweight
      male subjects, there was a positive correlation between BMI and SP, DP, PP, MP
      and HGS (P<0.05 for all). There was a positive correlation between BMI and SP in
      overweight male subjects (r = 0.5 P = 0.07, n = 13). A positive correlation was
      observed between BMI and rate-pressure product (r = 0.5, P = 0.45, n = 11) and
      BMI and HGS (r = 0.6, P = 0.05, n = 11) in overweight females. Our observations
      indicate that there are gender differences in the correlation between BMI and BP
      indices especially in underweight and overweight subjects. The observed
      differences between the three groups and gender differences in correlation
      between BMI and BP indices may be due to differences in autonomic function and or
      energy metabolism.

PMID- 16579402
TI  - The effects of right and left nostril breathing on cardiorespiratory and
      autonomic parameters.
AB  - The responses of right nostril breathing (RNB) and left nostril breathing (LNB)
      on cardio-respiratory and autonomic functions were investigated in healthy
      student volunteers of both sexes. The RNB and LNB groups comprised of 10 males
      and 10 females in each in age range of 17-22 years. Initially, in both groups
      control values of respiratory rate (RR), heart rate (HR), systolic blood pressure
      (SBP), diastolic blood pressure (DBF), peak expiratory flow rate (PEFR) and
      galvanic skin resistance (GSR) were recorded. The same parameters were recorded
      after 15 min (acute exposure) and 8 wks of training in RNB and LNB. In males RR
      (P<0.0001), SBP (P<0.05) and DBF (P<.05) fell significantly after 15 min of RNB.
      After 8 wks training in RNB, HR (P<0.01) decreased, SBP (P<0.001) declined more
      profoundly and RR (P<0.0001) and DBP (P<0.05) decrement was maintained. After 15
      min of LNB, RR (P<0.01), HR (P<0.01), SBP (P<0.001) and DBP (P<0.01) declined
      significantly, on 8 wks training, RR (P<0.0001) and HR (P<0.001) decreased
      further, the decrement in SBP (P<0.001) and DBP (P<0.01) was the same. In
      females, RR alone fell significantly (P<0.05) after 15 min RNB. After 8 wks RR
      decrement was more profound (P<0.0001) and DBP also declined significantly
      (P<0.01). Similarly, 15 min LNB resulted in significant reduction in RR (P<0.001)
      and HR (P<0.05) only. Following 8 wks, of training in LNB, in addition to RR
      (P<0.0001) and HR (P<0.05) decrement, SBP (P<0.01) and DBP (P<0.05) also fell
      significantly. Both in males and females, GSR did not change significantly
      (P>0.05) either after RNB or LNB (15 min/8 wks). PEFR rose significantly (P<0.05)
      only in females after 8 wks of LNB. The results suggest that there are no sharp
      distinctions between effects of RNB and LNB either acute exposure (15 min) or
      after training (8 wks). However, there is a general parasympathetic dominance
      evoked by both these breathing patterns.

PMID- 16579403
TI  - Influence of alternate nostril breathing on cardiorespiratory and autonomic
      functions in healthy young adults.
AB  - Alternate nostril breathing (ANB) may modulate cardio-respiratory and autonomic
      functions. However, the studies are scarce and results highly conflicting. The
      present study was conducted in healthy young volunteers comprising of males
      (n=20) and females (n=20) in range of 17-22 years. In both groups respiratory
      rate (RR/min), heart rate (HR/ min), systolic blood pressure (SBP; mm Hg),
      diastolic blood pressure (DBP; mm Hg), peak expiratory flow rate (PEFR; L/min)
      and galvanic skin resistance (GSR; microV) were recorded thrice; once as control
      and then after 15 min (acute exposure) and following 8 wks of training in ANB (15
      min daily). In males the control RR was 16.60 +/- 2.01, HR 75.75 +/- 11.07, SBP
      115.9 +/- 7.33, DBP 70.4 +/- 6.28 and PEFR 550.00 +/- 51.50. After 15 min of ANB
      RR (14.75 +/- 1.41, P<0.001), HR (68.45 +/- 12.41, P<0.01) and SBP (113.6 +/-
      6.04, P<0.05) fell significantly. After 8 wks of ANB training RR (12.35 +/- 1.35,
      P<0.0001), HR (63.20 +/- 11.11, P<0.001), SBP (109.5 +/- 5.61, P<0.001), declined
      to much greater extent and PEFR (571.50 +/- 46.26, P<0.01) rose significantly. In
      females the control RR was 17.25 +/- 1.89, HR-74.90 +/- 12.85, SBP-106.70 +/-
      6.91, DBP-68.70 +/- 5.52 and PEFR-394.50 +/- 44.89. After 15 min of ANB RR (15.05
      +/- 1.54, P<0.001) and HR (64.75 +/- 9.80, P<0.001) showed significant decline
      with concomitant rise in PEFR (407.00 +/- 2.31, P<0.05). Following 8 wks training
      the decrement in RR (12.60 +/-1.50, P<0.0001) and HR (63.30 +/- 8.65, P<0.001)
      was maintained. SBP (103.10 +/- 4.92, P<0.001) and DBP (65.8 +/- 5.54, P<0.001)
      decreased further and PEFR (421.00 +/- 38.51 P<0.001) rose, GSR was unaffected by
      ANB in both males and females. These results suggest that in general there is a
      tilt towards parasympathetic dominance by alternate nostril breathing. This
      breathing may be a useful adjuvant to medical therapy of hypertension and COPD.

PMID- 16579404
TI  - Does the level of instrumentation affect resting heart rate variability?

PMID- 16579405
TI  - Effect of Phyllanthus niruri on wound healing in rats.

PMID- 16579407
TI  - Interesting times.

PMID- 16579406
TI  - Physical properties of cold extract of curry leaves (Murraya koenigii spreng).

PMID- 16579408
TI  - PAH nurses welcome police beat.

PMID- 16579409
TI  - The Davies report.

PMID- 16579410
TI  - The importance of wage parity.

PMID- 16579411
TI  - QNU: helping people with HIV/AIDS in PNG.

PMID- 16579412
TI  - Making statements.

PMID- 16579413
TI  - Lessons in power: Lyndon Johnson revealed. A conversation with historian Robert
      A. Caro.
AB  - No one can lead who does not first acquire power, and no leader can be great who
      does not know how to use that power. The trouble is that the combination of the
      two skills is rare. Amassing power requires ambition, a focused pragmatism, and a
      certain ruthlessness that is often at odds with the daring, idealistic vision
      needed to achieve great things with that power. The tension is as real in
      business as it is in politics. This magazine is replete with examples of
      successful senior managers who could not make the switch from ambitious executive
      to corporate leader because they did not know what to do with the power they had
      so expertly accumulated. Robert Caro is a student of power. For the past 27
      years, the two-time Pulitzer prize-winning biographer of Robert Moses and Lyndon
      Johnson has focused on the question of how Johnson amassed and wielded power.
      Caro's deep understanding of the inner workings of power offers senior executives
      a nuanced picture of leadership at the highest level. In this wide-ranging
      conversation, Caro shares his insights about the nature of power, the complexity
      of ambition, and the role that the greater good can play in the making of a
      leader. Power doesn't always corrupt, he insists. But what it invariably does is
      reveal a leader's true nature. "Today, when CEOs have acquired more and more
      power to change our lives," Caro says,"they have become like presidents in their
      own right, and they, too, need to align themselves with something greater than
      themselves if they hope to become truly great leaders."

PMID- 16579414
TI  - The 47th annual McKinsey Awards. Recognizing excellence in management thinking.

PMID- 16579415
TI  - When should a leader apologize and when not?
AB  - When corporate leaders or the organizations they represent mess up, they face the
      difficult decision of whether or not to apologize publicly. A public apology is a
      risky move. It's highly political, and every word matters. Refusal to apologize
      can be smart, or it can be suicidal. Readiness to apologize can be seen as a sign
      of character or one of weakness. A successful apology can turn enmity into
      personal and organizational triumph--while an apology that's too little, too
      late, or too transparently tactical can open the floodgates to individual and
      institutional ruin. Since the stakes are so high, Kellerman says, leaders should
      not extend public apologies often or lightly. One or more of the following
      conditions should apply: The apology is likely to serve an important purpose. The
      offense is of serious consequence. It's appropriate that the leader assume
      responsibility for the offense. The leader is the only one who can get the job
      done. The cost of saying something is likely lower than the cost of staying
      silent. The author draws her conclusions from hard data and abundant anecdotal
      evidence, examining notoriously bad apologizers as well as exceptionally good
      ones. While selectivity is key, good apologies usually do work. What constitutes
      a good apology? Acknowledgment of the mistake or wrongdoing, acceptance of
      responsibility, expression of regret, and assurance that the offense will not be
      repeated.

PMID- 16579416
TI  - Localization--the revolution in consumer markets.
AB  - Standardization has been a powerful strategy in consumer markets, but it's
      reached the point of diminishing returns. And diversity is not the only chink in
      standardization's armor: Attempts to build stores in the remaining attractive
      locations often meet fierce resistance from community activists. From California
      to Florida to New Jersey, neighborhoods are passing ordinances that dictate the
      sizes and even architectural styles of new shops. Building more of the same--long
      the cornerstone of retailer growth--seems to be tapped out as a strategy. Of
      course, a company can't customize every element of its business in every
      location. Strategists have begun to use clustering techniques to simplify and
      smooth out decision making and to focus their efforts on the relatively small
      number of variables that usually drive the bulk of consumer purchases. The
      customization-by-clusters approach, which began as a strategy for grocery stores
      in 1995, has since proven effective in drugstores, department stores, mass
      merchants, big-box retailers, restaurants, apparel companies, and a variety of
      consumer goods manufacturers. Clustering sorts things into groups, so that the
      associations are strong between members of the same cluster and weak between
      members of different clusters. In fact, by centralizing data-intensive and scale
      sensitive functions (such as store design, merchandise assortment, buying, and
      supply chain management), localization liberates store personnel to do what they
      do best: Test innovative solutions to local challenges and forge strong bonds
      with communities. Ultimately, all companies serving consumers will face the
      challenge of local customization. We are advancing to a world where the
      strategies of the most successful businesses will be as diverse as the
      communities they serve.

PMID- 16579417
TI  - Match your innovation strategy to your innovation ecosystem.
AB  - High-definition televisions should, by now, be a huge success. Philips, Sony, and
      Thompson invested billions of dollars to develop TV sets with astonishing picture
      quality. From a technology perspective, they've succeeded: Console manufacturers
      have been ready for the mass market since the early 1990s. Yet the category has
      been an unmitigated failure, not because of deficiencies, but because critical
      complements such as studio production equipment were not developed or adopted in
      time. Under-performing complements have left console producers in the position of
      offering a Ferrari in a world without gasoline or highways--an admirable
      engineering feat, but not one that creates value for customers. The HDTV story
      exemplifies the promise and peril of innovation ecosystems--the collaborative
      arrangements through which firms combine their individual offers into a coherent,
      customer-facing solution. When they work, innovation ecosystems allow companies
      to create value that no one firm could have created alone. The benefits of these
      systems are real. But for many organizations the attempt at ecosystem innovation
      has been a costly failure. This is because, along with new opportunities,
      innovation ecosystems also present a new set of risks that can brutally derail a
      firm's best efforts. Innovation ecosystems are characterized by three fundamental
      types of risk: initiative risks--the familiar uncertainties of managing a
      project; interdependence risks--the uncertainties of coordinating with
      complementary innovators; and integration risks--the uncertainties presented by
      the adoption process across the value chain. Firms that assess ecosystem risks
      holistically and systematically will be able to establish more realistic
      expectations, develop a more refined set of environmental contingencies, and
      arrive at a more robust innovation strategy. Collectively, these actions will
      lead to more effective implementation and more profitable innovation.

PMID- 16579418
TI  - Manage customer-centric innovation--systematically.
AB  - No matter how hard companies try, their approaches to innovation often don't grow
      the top line in the sustained, profitable way investors expect. For many
      companies, there's a huge difference between what's in their business plans and
      the market's expectations for growth (as reflected in firms' share prices, market
      capitalizations, and P/E ratios). This growth gap springs from the fact that
      companies are pouring money into their insular R&D labs instead of working to
      understand what the customer wants and using that understanding to drive
      innovation. As a result, even companies that spend the most on R&D remain starved
      for both customer innovation and market-capitalization growth. In this article,
      the authors spell out a systematic approach to innovation that continuously fuels
      sustained, profitable growth. They call this approach customer-centric
      innovation, or CCI. At the heart of CCI is a rigorous customer R&D process that
      helps companies to continually improve their understanding of who their customers
      are and what they need. By so doing, they consistently create or improve their
      customer value proposition. Customer R&D also focuses on better ways of
      communicating value propositions and delivering the complete experience to real
      customers. Since so much of the learning about customers and so much of the
      experimentation with different segmentations, value propositions, and delivery
      mechanisms involve the people who regularly deal with customers, it is absolutely
      essential for frontline employees to be at the center of the CCI process. Simply
      put, customer R&D propels the innovation effort away from headquarters and the
      traditional R&D lab out to those closest to the customer. Using the example of
      the luggage manufacturer Tumi, the authors provide a step-by-step approach for
      achieving true customer-centric innovation.

PMID- 16579419
TI  - Your loyalty program is betraying you.
AB  - Even as loyalty programs are launched left and right, many are being scuttled.
      How can that be? These days, everyone knows that an old customer retained is
      worth more than a new customer won. What is so hard about making a simple loyalty
      program work? Quite a lot, the authors say. The biggest challenges include
      clarifying business goals, engineering the reward structure, and creating
      incentives powerful enough to change buying behavior but not so generous that
      they erode margins. Additionally, companies have to sort out the puzzles of
      consumer psychology, which can result, for example, in two rewards of equal
      economic value inspiring very different levels of purchasing. In their research,
      the authors have discovered patterns in what the successful loyalty programs get
      right and in how the others fail. Together, their findings constitute a tool kit
      for designing something rare indeed: a program that won't do you wrong. To begin
      with, it's important to know exactly what a loyalty program can do. It can keep
      customers from defecting, induce them to consolidate certain purchases with one
      seller (in other words, win a greater share of wallet), prompt customers to make
      additional purchases, yield insight into their behavior and preferences, and turn
      a profit. A program can meet these objectives in several ways--for instance, by
      offering rewards (points, say, or frequent-flier miles) divisible enough to
      provide many redemption opportunities but not so divisible that they fail to lock
      in customers. Companies striving to generate customer loyalty should avoid five
      common mistakes: Don't create a new commodity, which can result in price wars and
      other tit-for-tat competitive moves; don't cater to the disloyal by making
      rewards easy for just anyone to reap; don't reward purchasing volume over
      profitability; don't give away the store; and, finally, don't promise what can't
      be delivered.

PMID- 16579420
TI  - The unexpected benefits of Sarbanes-Oxley.
AB  - In the wake of a series of gross corporate abuses around the turn of the century,
      Congress passed Sarbanes-Oxley, which was intended to make corporate governance
      more rigorous, financial practices more transparent, and management criminally
      liable for lapses. The first year of implementation was costly and onerous, far
      more so than companies had been led to expect. In the view of a few open-minded
      firms, however, the second year of compliance turned out to be not only less
      costly and less onerous (as doing something for the second time usually turns out
      to be), but a source of valuable insights into operations, which management has
      translated into improved efficiencies and cost savings. The areas of improvement
      go well beyond technical statutory compliance. They include a strengthened
      control environment; more reliable documentation; increased audit committee
      involvement; better, less burdensome compliance with other statutory regimes;
      more standardized processes for IT and other functions; reduced complexity
      oforganizational processes; better internal controls within partner companies;
      and more effective use of both automated and manual controls. The result is not
      only shareholder protection, the official purpose of the act, but also enhanced
      shareholder value. More than a year since the first deadline arrived, Sarbanes
      Oxley still inspires fear--of enforcement actions, of the stock market's reaction
      to a deficiency, and of personal liability. Fear can be a powerful generator of
      upstanding conduct. But businesses run on discovering and creating value.
      Companies need to start viewing Sarbanes-Oxley as an ally in that effort.

PMID- 16579421
TI  - Searching for a single voice. Various factors and groups affect the quality
      movement's quest to coalesce around a main strategy that will improve patient
      care.
AB  - According to industry experts, there are too many cooks in the quality kitchen,
      each with different recipes and ingredients for the perfect way to improve
      patient safety and care. Some, like Cassy Horack, left, who is director of her
      hospital's quality initiatives, say that hospitals should work on quality from
      the inside out. Others believe universal benchmarks should determine what is
      quality care.

PMID- 16579422
TI  - For-profits' share climbs. 17% of hospitals are now investor-owned.

PMID- 16579423
TI  - Mergers boost prices: study. Consolidations in '90s cited for likely hurting
      quality.

PMID- 16579424
TI  - Payments may fall. CMS has come up with a list of some 100 procedures.

PMID- 16579425
TI  - Dodging conflicts? AAAASF unit raises questions for accrediting group.

PMID- 16579426
TI  - Looking to diversify. Ascension putting 30% of portfolio into alternatives.

PMID- 16579427
TI  - Ban has fiscal repercussions.

PMID- 16579428
TI  - Improving on improvement. Number of quality signposts is narrowing, but patients
      still need better guidance.

PMID- 16579429
TI  - We don't want you'. Squabbles over capital investment, support for expansion
      prompt N.C. hospital to drop for-profit HCA for not-for-profit Novant.

PMID- 16579430
TI  - By the numbers. Most profitable critical-access hospitals ranked by operating
      margin, based on 2004 Medicare cost report data.

PMID- 16579431
TI  - Med-mal rates are flat: study.

PMID- 16579432
TI  - On call in hell.

PMID- 16579434
TI  - 'What did they sew you up with?'.

PMID- 16579433
TI  - 'I had a lot to be thankful for'.

PMID- 16579435
TI  - A legacy of love and hope.

PMID- 16579436
TI  - Should we export illness or health?

PMID- 16579437
TI  - [Energy metabolism in halophilic and alkalophilic bacteria].
AB  - This review summarizes the recent data on the energy metabolism of acetogenic
      bacteria isolated from saline and soda lakes. It provides a general description
      of saline and soda lakes as microbial habitats, performs a comparative analysis
      of the energy metabolism of neutrophilic acetogens, considers the adaptation
      strategies of halophilic and alkalophilic acetogens to high salinity and high pH
      values, while also discussing the mechanisms of energy accumulation under auto-
      and organotrophic conditions.

PMID- 16579438
TI  - [Carboanhydrase activity in halophilic anaerobes from soda lakes].
AB  - The activity and cellular localization of carboanhydrase (CA) in two alkaliphilic
      anaerobes growing in soda lakes at pH 9-10 was studied. CA activity in the cell
      extracts of the acetogenic bacterium Natroniella acetigena was comparable to that
      of the neutrophilic acetogens. Hydrogenotrophically grown cells of
      Desulfonatronum lacustre exhibited higher CA activity compared to the cells grown
      on media with formate. High CA activity in the cytoplasmic fraction and the
      absence of high activity in the extracellular fraction were demonstrated. We
      propose that the cytoplasmic CA in alkaliphilic sulfate-reducers participates in
      conversion of bicarbonate to CO2, which is reduced in the cell to acetate via the
      acetyl-CoA pathway.

PMID- 16579440
TI  - [Screening of yeasts producing stable L-lactate cytochrome c oxidoreductase and
      regulation of enzyme synthesis].
AB  - Screening of strains producing a stable form of L-lactate cytochrome c
      oxidoreductase (flavocytochrome b2, FC b2) was carried out among 14 yeast
      species. Enzyme activity was detected in polyacrylamide gel after the
      electrophoresis of cell-free extracts. The FC b2 of Hansenula polymorpha,
      Rhodotorula pilimanae, and Kluyveromyces lactis are characterized by high
      thermostability; in particular, the FC b2 of H. polymorpha retains its activity
      and tetrameric structure even after heating at 60 degrees C for 10 min.
      Constitutive synthesis of FC b2 was observed in H. polymorpha grown on either
      glucose, ethanol, or glycerol. L-Lactate induces de novo synthesis of FC b2, as
      proved by the use of cycloheximide, an inhibitor of protein synthesis.

PMID- 16579439
TI  - [Biologically active lipids in fungi of the Pilobolaceae family].
AB  - The synthesis of bioactive lipids in three species of lower mycelial fungi of the
      genus Pilaira, the family Pilobolaceae, has been studied. The pigmentation of
      these fungi was found to be determined by the presence of beta-carotene in
      amounts of 14.8 (P. moreaui), 115.7 (P. caucasica), and 312.9 (P. anomala)
      microg/g. The fatty acid profiles of the fungi, which are distinguished by the
      presence of up to 50% essential fatty acids, is typical of zygomycetes of the
      order Mucorales. The fungi grown in submerged cultures showed a correlation of
      the unsaturation indices of their fatty acids and the contents of beta-carotene.

PMID- 16579441
TI  - [The effect of inactivation of the exo- and endopolyphosphatase genes PPX1 and
      PPN1 on the level of different polyphosphates in the yeast Saccharomyces
      cerevisiae].
AB  - The inactivation of the PPX1 and PPN1 genes, which encode the major enzymes of
      polyphosphate degradation (exopolyphosphatase and endopolyphosphatase,
      respectively), was found to exert different effects on the content of different
      polyphosphates in the yeast Saccharomyces cerevisiae. The content of relatively
      low-molecular-weight acid-soluble polyphosphates in mutant yeast strains is
      inversely proportional to the exopolyphosphatase activity of the cytosol. At the
      same time, the mutation of these genes exerts no effect on salt-soluble
      polyphosphates. The content of high-molecular-weight alkali-soluble
      polyphosphates increases twofold in a mutant with inactivated genes of both
      exopolyphosphatase and endopolyphosphatase. The data obtained confirm the earlier
      suggestion that the metabolic pathways of particular polyphosphates in yeasts are
      different.

PMID- 16579442
TI  - [Analysis of phospholipids in bifidobacteria].
AB  - Methods of preparative chromatography on silica gel columns were used for
      obtaining preparations of polar lipids of bifidobacteria. Studies of the
      preparations by one-dimensional and two-dimensional TLC demonstrated that
      diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine
      (PE), and phosphatidylcholine (PC) were the predominant phospholipids; minor
      phospholipids (phosphorus-containing components present in considerably lower
      amounts) included phosphatidylinositol (PI) and lyso-phosphatidylcholine (lyso
      PC). Parameters of qualitative composition of phospholipids and glycolipids may
      serve as a set of chemotaxonomic markers in modem procedures for identifying
      Bifidobacterium species.

PMID- 16579443
TI  - [Degradation of proteinaceous substrates by xylotrophic basidiomycetes].
AB  - The ability of various xylotrophs to produce extracellular proteolytic enzymes
      has been studied, with emphasis on medium-related factors regulating their
      secretion. Direct measurement of proteolytic activity in the culture liquid and
      postelectrophoresis determination of protease activity in polyacrylamide gel
      copolymerized with gelatin demonstrated that the secreted enzymes are
      quantitatively and qualitatively diverse. Activity levels of extracellular
      proteolytic enzymes strongly depend on pH and contents of protein and
      carbohydrate in the medium. All secreted proteases notably differed in molecular
      weight (of 51 kDa or higher and in excess of 95 kDa) and belonged mostly to two
      classes of proteolytic enzymes (serine proteases and metalloproteinases).

PMID- 16579444
TI  - [A bioelectrochemical study of a suspension of Escherichia coli cells
      metabolizing glucose and lactose].
AB  - The metabolism of glucose and lactose in E. coli K-12 cells has been studied
      using a bioelectrochemical (BEC) approach. The magnitude and the duration of the
      response of a BEC anode were found to be functions of the composition of nutrient
      media and the concentration of bacterial cells. The amount of electricity that is
      generated enzymatically during the metabolism of a particular substrate depends
      on the activity of the relevant enzymes. This suggests that the BEC approach can
      be used for evaluating the activity of particular enzyme systems.

PMID- 16579445
TI  - [Chemotaxis and growth of Bradyrhizobium japonicum in the presence of fine
      dispersed silica].
AB  - The chemotactic properties of the soybean nodule bacterium Bradyrhizobium
      japonicum were studied in the presence of synthetic fine-dispersed materials. It
      was shown that fine-dispersed silica (FDS) and its variety modified with aluminum
      oxide (MFDS) reduce bacterial chemotaxis to glucose. In addition, FDS increases
      the irregular motility of B. japonicum, and MFDS decreases it. This is in
      agreement with the effect of the materials on the rate of nodule bacterium
      growth.

PMID- 16579446
TI  - [Effect of Congo red on the motility of the bacterium Azospirillum brasilense].
AB  - In semiliquid laboratory media, the bacterium Azospirillum brasilense migrates
      with the formation of swarming rings. It is demonstrated that adsorption of the
      sulfonated azodye Congo Red confers on A. brasilense the ability to consistently
      spread in a semiliquid agar and form microcolonies. Spontaneous variants of A.
      brasilense with rapid swarming are described, as well as variants that swarm in
      the presence of Congo Red. It is assumed that at least two types of compounds are
      formed, which are (a) necessary for swarming and/or spreading with the formation
      of microcolonies and (b) capable of interacting with Congo Red.

PMID- 16579447
TI  - [Phylogenetic diversity and activity of anaerobic microorganisms of high
      temperature horizons of the Dagang Oilfield (China)].
AB  - The number of microorganisms of major metabolic groups and the rates of sulfate
      reducing and methanogenic processes in the formation waters of the high
      temperature horizons of Dagang oilfield have been determined. Using cultural
      methods, it was shown that the microbial community contained aerobic bacteria
      oxidizing crude oil, anaerobic fermentative bacteria, sulfate-reducing bacteria,
      and methanogenic bacteria. Using cultural methods, the possibility of methane
      production from a mixture of hydrogen and carbon dioxide (H2 + CO2) and from
      acetate was established, and this result was confirmed by radioassays involving
      NaH14CO3 and 14CH3COONa. Analysis of 16S rDNA of enrichment cultures of
      methanogens demonstrated that these microorganisms belong to Methanothermobacter
      sp. (M. thermoautotrophicus), which consumes hydrogen and carbon dioxide as basic
      substrates. The genes of acetate-utilizing bacteria were not identified.
      Phylotypes of the representatives of Thermococcus spp. were found among 16S rDNAs
      of archaea. 16S rRNA genes of bacterial clones belong to the orders
      Thermoanaerobacteriales (Thermoanaerobacter, Thermovenabulum, Thermacetogenium,
      and Coprothermobacter spp.), Thermotogales, Nitrospirales (Thermodesulfovibrio
      sp.) and Planctomycetales. 16S rDNA of a bacterium capable of oxidizing acetate
      in the course of syntrophic growth with H2-utilizing methanogens was found at
      high-temperature petroleum reservoirs for the first time. These results provide
      further insight into the composition of microbial communities of high-temperature
      petroleum reservoirs, indicating that syntrophic processes play an important part
      in acetate degradation accompanied by methane production.

PMID- 16579448
TI  - [The properties of hydrocarbon-oxidizing bacteria isolated from the oilfields of
      Tatarstan, Western Siberia, and Vietnam].
AB  - Eleven strains of hydrocarbon-oxidizing bacteria, isolated from oilfields,
      representing the genera Rhodococcus, Gordonia, Dietzia, and Pseudomonas, were
      characterized as mesophiles and neutrophiles. Rhodococci were halotolerant
      microorganisms growing in a media containing up to 15% NaCl. All the strains
      oxidized n-alkanes of crude oil. An influence of the cultivation temperatures (28
      or 45 degrees C) and organic supplements on the degradation of C12-C30 n-alkanes
      in oxidized oil by two bacterial strains of the genus Pseudomonas was shown. The
      introduction of acetate, propionate, butyrate, ethanol, and sucrose led mainly to
      the decreased oxidation of petroleum paraffins. At certain cultivation
      temperatures, the addition of volatile fatty acid salts increased the content of
      individual n-alkanes in oxidized vs. crude oil.

PMID- 16579449
TI  - [Investigation of relationships between marine diatoms and the bacterium Listeria
      monocytogenes].
AB  - Relationships between marine diatoms and the bacterium Listeria monocytogenes
      have been studied by routine algological methods and high-resolution video
      enhanced differential interference contrast light microscopy. The study showed
      that the relationship between the listeria and the benthic diatom Navicula sp.
      has a parasitic character, whereas the relationship between the listeria and the
      planktonic diatom Phaeodactylum tricornutum is protocooperative.

PMID- 16579450
TI  - [Symbiosis between the nodule bacterium Sinorhizobium meliloti and alfalfa
      (Medicago sativa) under salinization conditions].
AB  - Two hundred forty-three isolates of alfalfa nodule bacteria (Sinorhizobium
      meliloti) were obtained from legume nodules and soils sampled in the northern
      Aral region, experiencing secondary salinization. Isolates obtained from nodules
      (N isolates) were significantly more salt-tolerant than those from soils (S
      isolates) when grown in a liquid medium with 3.5% NaCl. It was found that wild
      species of alfalfa, melilot, and trigonella preferably formed symbioses with salt
      tolerant nodule bacteria in both salinized and nonsalinized soils. Only two
      alfalfa species, Medicago falcata and M. trautvetteri, formed efficient symbioses
      in soils contrasting in salinity. The formation of efficient symbiosis with
      alfalfa in the presence of 0.6% NaCl was studied in 36 isolates (N and S)
      differing in salt tolerance and symbiotic efficiency. Fifteen isolates formed
      efficient symbioses in the presence of salt. The increase in the dry weight of
      the plants was 25-68% higher than in the control group. The efficiency of
      symbiotic interaction under salinization conditions depended on the efficiency of
      the isolates under standard conditions but did not correlate with the source of
      nodule bacteria (soil or nodule) or their salt tolerance. The results indicate
      that nodule bacterium strains forming efficient symbioses under salinization
      conditions can be found.

PMID- 16579451
TI  - [Distribution, diversity, and activity of sulfate-reducing bacteria in the water
      column in Gek-Gel Lake, Azerbaijan].
AB  - The distribution and activity of sulfate-reducing bacteria (SRB) in the water
      column of the alpine meromictic Gek-Gel lake were studied. Apart from traditional
      microbiological methods based on cultivation and on measuring the process rates
      with radioactive labels, in situ fluorescent hybridization (FISH) was used, which
      enables identification and quantification without cultivating organisms. The peak
      rate of sulfate reduction, 0.486 microg S/(l day), was found in the chemocline at
      33 m. The peak SRB number of 2.5 x 106 cells/ml, as determined by the end-point
      dilutions method on selective media, was found at the same depth. The
      phylogenetic position of the SRB, as determined by FISH, revealed the
      predominance of the Desulfovibrio spp., Desulfobulbus spp., and Desulfoarculus
      spp./Desulfomonile spp. groups. The numbers of spore-forming Desulfotomaculum
      spp. increased with depth. The low measured rates of sulfate reduction
      accompanied with high SRB numbers and the predominance of the groups capable of
      reducing a wide range of substrates permit us to propose utilization of electron
      acceptors other than sulfate as the main activity of the SRB in the water column.

PMID- 16579453
TI  - [Study of intraspecific variations of the bacterium Lactococcus lactis in
      adaptation to high acidity of the medium].
AB  - This paper reports on the study of acid tolerance of lactic acid bacteria as a
      property of cells, determining their ability to divide efficiently and retain
      viability under conditions of increased nutrient medium acidity during bacterial
      growth. The bacteria of the strain TV2, isolated from a self-soured curd, similar
      to the bacteria of the strain STE05 (Russian National Collection of Industrial
      Microorganisms), were assigned to the species Lactococcus lactis according to
      their G+C composition (36.7-36.5 mol %) and the high level of DNA-DNA
      hybridization (93%). However, these strains were essentially different in the
      number and size of the plasmids and the chromosomal DNA restriction fragments, as
      well as in the sensitivity to phages of lactic acid bacteria. It was found that
      bacteria of the strain TV2 were stable (i.e., they divided efficiently at a pH as
      low as 5.3) and tolerant to the lactic acid that they produced while growing
      (i.e., they retained viability at pH 4.4). Bacteria of the strain STE05 lacked
      acid tolerance (at pH below 6.5, growth was retarded, and pH 5.0 was the lowest
      value at which the cells remained viable). The acid tolerance and phage
      resistance of TV2 bacteria are likely to characterize their higher adaptive
      capacity in comparison with STE05 bacteria. Acid tolerance is inherited in a
      stable manner and retained by the segregants of TV2 strain obtained in the course
      of long-term storage of the bacteria. Specifically, the strains TV29, TV13, and
      TV 229, which displayed this property, had altered physiological and biochemical
      characteristics (accumulation of biomass and fermentation of lactose) in spite of
      their genetic identity to the original strain (pulsed-field gel electrophoresis
      of chromosomal DNA restriction fragments).

PMID- 16579452
TI  - [Bacteria of the genus Burkholderia as a typical component of the microbial
      community of sphagnum peat bogs].
AB  - Bacteria of the genus Burkholderia are a typical component of the microbial
      complex of sphagnum peat bogs and constitute a substantial portion of the aerobic
      chemoorganotrophic isolates which are routinely obtained from these environments
      on acidic nutrient media. The ecophysiological characteristics of the 27 strains
      of such organisms, which were isolated from the peat of acidic sphagnum bogs of
      the boreal and tundra zones of Russia, Canada, and Estonia, were investigated in
      the present paper. The overwhelming majority of the Burkholderia strains isolated
      from these bogs were phylogenetically close to the species B. glathei, B.
      phenazinium, B. fungorum, and B. caryophylli, the typical inhabitants of soil and
      plant rhizosphere. The bog isolates utilized a broad range of substrates as
      carbon and energy sources, including organic acids, sugars, polyalcohols, and
      certain aromatic compounds. All the strains studied were capable of growth on
      nitrogen-free media. They developed in the pH ranges of 3.5 to 7.4 and from 3 to
      37 degrees C, with the optima at pH 5-7 and 11-23 degrees C, respectively. They
      were therefore moderately acidophilic, psychroactive, dinitrogen-fixing
      microorganisms well adapted to the conditions of acidic northern sphagnum bogs.

PMID- 16579454
TI  - [Method for rapid DNA extraction from bacterial communities of different soils].
AB  - A method for indirect DNA extraction from various soils significantly differing
      in their physicochemical properties has been developed. The proposed method is
      based on cell desorption from soil particles using a Tris-EDTA (TE) buffer
      supplemented with polyvinylpolypyrrolydone (PVPP) and sodium dodecylsulfate
      (SDS). Subsequent cell lysis and purification of DNA preparations methods based
      on alkaline lysis followed by chromatography on ion-exchange resins were
      described by us earlier. The purity of the DNA preparations obtained did not
      depend on the type of soil. It was shown that the DNA preparations can be used
      for the amplification of rather large fragments, e.g., sequences spanning the
      complete 16S rRNA gene.

PMID- 16579455
TI  - [Diversity of halophilic archaea in hypersaline lakes of Inner Mongolia, China].
AB  - The aims of this work were to explore the diversity of halophilic archaea in
      hypersaline lakes of Inner Mongolia, China and to collect novel halophilic
      archaea. One hundred and sixty-five halophilic archaea were isolated from the
      three different types of hypersaline lakes (Erliannor, shangmatala and Xilin soda
      lake) in Inner Mongolia. By analysis of the restriction patterns of amplified 16S
      rDNA (ARDRA) with the enzyme Afa I and Hae II, respectively, the isolates were
      clustered into 14 genotypes, and the representatives of each genotype were
      randomly chosen for the determination of 16S rDNA sequence. The phylogenetic
      analysis revealed that all of the isolates were clustered into 10 groups:
      Halorubrum, Natronococcus, Natronorubrum, Haloterrigena, Halorhabdus,
      Halobiforma, Haloarcula, Haloferax and other two unknown groups. Dominant
      isolates were related to Halorubrum spp. in all three lakes. Some of the isolates
      studied showed less affiliation with known taxa ( <98% sequence similarity) and
      may represent novel taxa. Two isolates HXH33 and HSH33 showed very less
      affiliation with known genus ( < 93% sequence similarity) and may represent two
      new genera. These results suggest that diverse archaea exist in and the unknown
      archaea thrive in the hypersaline lakes of Inner Mongolia.

PMID- 16579456
TI  - [Identification and characterization of a Bacillus amyloliquefaciens with high
      antifungal activity].
AB  - Plant disease can cause serious crop losses, and chemical control of disease is
      costly both to the environment and to the farmer. Some microorganism can produce
      the substance which has the preventing and exterminating functions to plant
      pathogens. These substances are valid to plant pathogens with only lower
      concentration, in addition the substances do not remain in soil and crops without
      being decomposed. If composization is performed with the microorganism, or the
      microorganism is mixed into compost, the functional compost having preventing and
      exterminating action will be made out and that can be more useful to
      environmental preservation. In order to screen antifungal bacteria for use in
      biological control, 200 compost samples were taken from different regions in
      China, over 10 bacterium with clear antifungal activity were isolated from
      composts, among them, strain Q-12 exhibited the highest antifungal activity which
      was strongly inhibits the growth of many plant pathogenic fungi such as Fusarium
      oxysporum and Rhizoctonia solan. According to the characteristics of morphology,
      physiology and biochemistry tests (API 50 CHB/E system) and the comparison of 16S
      rDNA sequence, the strain Q-12 was similar to B. subtilis and B.
      amyloliquefaciens. Some specific genes yyaR, yyaO and tetB, which have previously
      been shown to be effective for resolving these closely related taxa of the B.
      subtilis group, were analysed to clarify further the classification of Q-12, and
      two pairs of primers YyaR _ F/TetB _ R and YyaO _ F/TetB _ R were designed. From
      the analysis of fingerprints obtained with the two primers, strain Q-12 and B.
      amyloliquefaciens showed identical genomic fingerprints with primers YyaR _
      F/TetB R, indicating their closely genetic relationship, and was identified as B.
      amyloliquefaciens. In the investigation of the culture condition, growth was
      carried out in a basal medium and gradually supplemented with the various
      ingredients to be investigated. The major ingredients being investigated included
      carbon sources, nitrogen sources and inorganic salts. The optimum medium and
      culture conditions of the strain all were studied with single factor test. The
      strain is easy to cultivate, and the optimal antibiotic production condition is
      growth in a medium (5 g/L glucose, 1 g/L NH4Cl, 0.8 g/L beef extract, 5 g/L
      MgCl2, pH 6.0) at 33 degrees C for 40 h. A number of Bacillus strains have proven
      safe over many years as a nonpathogenic species and are consumed in ton
      quantities in several human food preparations. Strains of Bacillus have several
      advantages over other biocontrol bacteria in that they are often soil isolates
      capable of sporulation, easy to cultivate and store, and some strains have been
      shown to increase yields of various crops.

PMID- 16579457
TI  - [Rapid identification of Riemerella anatipestifer on the basis of specific PCR
      amplifying 16S rDNA].
AB  - Riemerella anatipestifer (RA) infection is the main disease causing severe losses
      in duck production. Because RA is characterized more by the absence than by the
      presence of specific phenotypic properties and different scholar had the
      different results of biochemical detection, it can't always be identified quickly
      and correctly only by the phenotypic properties or biochemical characteristics.
      The research object was to develop a species specific PCR method for RA
      detection. Because of the conserved structure of rRNA and appropriate size of 16S
      rRNA, a multiple alignment of 16S rDNA (gene coding 16S rRNA) was processed among
      RA, Escherichia coli, Pasteurella multocida, Salmonella enteritidis and
      Salmonella gallinarum, which are the main bacteria causing duck diseases. A pair
      of species specific primers named 190f and 843r were selected from the variable
      regions of 16S rDNA depending on the result of multiple alignment. Using BLAST on
      NCBI website for a sequence similarity search, the results showed that this pair
      of primers had very high specificity, except for having a lower sequence
      similarity with some species of Flavobacterium and Chryseobacterium. A PCR assay
      was performed and the template was extracted using the bacteria genomic DNA
      extraction kit and boiling method respectively. A chelate resin named Chelex 100
      was used in the boiling method at the same time. Under the annealing temperature
      of 60 degrees C, all the 26 RA strains, including 19 representative strains of
      serotypes 1 to approximately 19 and 7 domestic isolated strains, showed the same
      654bp fragment after PCR, while there was no amplification with isolates of other
      bacterial species. Also a series of sensitivity experiments were performed and
      proved that the detection limit of this method was 50pg genomic DNA, 1.5 x 10(6)
      CFU/mL and 15 CFU/mL, when the template was prepared with genomic DNA extraction
      kit, only boiling method and boiling method with Chelex 100 respectively. 12
      clinical cases which were probably infected with RA were chosen to identify the
      accuracy and sensitivity of this PCR method. Several other conventional detecting
      methods including bacteria isolating, differentiating culture, biochemical
      experiments and serotyping were used at the same time. The templates of PCR were
      extracted from brains or livers by boiling method with Chelex 100. Finally, 3
      cases were identified as RA infection by the conventional methods and 4 by the
      PCR method, which proved the good accuracy and sensitivity of the PCR method.
      Thus, this PCR assay provides a rapid and accurate method for identification of
      Riemerella anatipestifer. It will help to make the final decision in clinical
      diagnose or species identification, especially when a new serotype or sub
      serotype of RA comes up.

PMID- 16579458
TI  - [Identification of two new genes involved in swimming motility of Pseudomonas
      aeruginosa].
AB  - Pseudomonas aeruginosa, a typical opportunistic pathogen, has a single polar
      flagella which provides swimming motility and virulence. Twelve of insertional
      mutants with Mu transposition complexes into genomic DNA of Pseudomonas
      aeruginosa were screened on the changes of swimming motility. After gene cloning
      and DNA sequencing of those mutants, ten of them were illustrated that defective
      mutations on swimming motility were caused by insertions of Mu transposon into 10
      of different functional genes which may involved in biosynthesis of flagella and
      gene regulations, but another two mutants were resulted from the insertion of two
      new genes (PA2950, PA5022) with function unknown. Observation of these two
      mutants with an integrity flagellum under electron microscope showed that two new
      genes were not involved in construction of flagella, but probably in energy
      metabolism and gene regulation of swimming motility.

PMID- 16579459
TI  - [Knockout of the ccpA gene in Bacillus subtilis and influence on riboflavin
      production].
AB  - Bacillus subtilis uses glucose as preferred source of carbon and energy, but
      expression of many genes involved in central pathways is often repressed or
      activated in the presence of glucose. This phenomenon is called carbon catabolite
      repression (CCR) in B. subtilis, which is mainly mediated by the global regulator
      CcpA encoded by ccpA gene. In the present of glucose, the genes encoding
      glycolytic enzymes are induced; the genes responsible for the production of
      acetate from pyruvate are induced also, however, the genes required for Krebs
      cycle are repressed. Sometimes, this leads to lower production in fed-batch
      fermentation. In this study, ccpA gene of the riboflavin producing train B.
      subtilis24/ pMX45 was disrupted using homologous recombination technology and a
      ccpA mutant B. subtilis24A1/pMX45 was constructed. The comparison of shake-flask
      fermentation indicates B. subtilis24A1/pMX45 could grow normally in culture
      medium containing excess glucose; and the ratio of glucose consumption increased
      remarkably, for example, 10% glucose can be consumed within 70 hours, biomass
      increased to 1.5 x 10(9)cell/mL; at the same time the accumulation amount of
      overflow metabolite decreases. Especially, when fermenting with culture medium
      containing 8% and 10% glucose respectively, the yields of riboflavin increase 62%
      and 95% than B. subtilis24/pMX45. These results demonstrate knockout of ccpA gene
      can relieve carbon catabolite repression and lead to the alteration of central
      catabolite flux in favor of synthesis of riboflavin, so the yield of riboflavin
      can be enhanced significantly.

PMID- 16579460
TI  - [Cloning of the ectoine biosynthesis gene ectABC from Halomonas sp. BYS-1 and
      salt stressed expression in Escherichia coli].
AB  - Ectoine was the main compatible solute of moderately halophilic bacteria. In
      order to clone the ectABC gene which involved in the ectoine biosynthesis pathway
      from total DNA of moderately halophilic bacteria Halomonas sp. BYS-1, firstly a
      750bp fragment of ectABC gene was amplified by PCR using combinations of forward
      primers and reverse primers designed according to the ectABC genes of Halomonas
      elongata 2851T and Halomonas elongata DSM3043. Then the upstream and downstream
      sequences of the 750bp fragment were amplified by SEFA PCR (SElf-Formed Adaptor
      PCR), a new PCR method amplified relatively long flanking sequences from tagged
      sequences in a simple way without enzyme excision and ligation. The 3532bp
      fragment include 2423bp ectABC, 980bp upstream sequences and 129bp downstream
      sequences were cloned from Halomonas sp. BYS-1 using a pair of conserved primers
      designed according to acquired sequences by SEFA PCR. The GenBank accession
      number of the 3532bp fragment is DQ017757. ORF analysis revealed that ectA, ectB,
      ectC cluster to an operon, the size of ectA, ectB, and ectC were 573bp, 1251bp
      and 387bp respectively. The predicted molecular masses of the encoded proteins
      were 21.1kDa (191 amino acids, EctA), 45.7 kDa (417 amino acids, EctB), and 14.5
      kDa (129 amino acids, EctC) respectively. The 3532bp fragment was ligated to the
      MCS site of vector pUC19 and transformed E. coli DH5alpha to construct E. coli
      (pUC19ECT). Transformant E. coli (pUC19ECT) could synthesis ectoine under salt
      stress, the intracellular ectoine level were 7.1, 19.4 and 32.3 micromol/(g x dry
      x wt) when the salinities of the mediums were 0, 0.4 and 0.8mol/L sodium chloride
      respectively. But the accumulation of ectoine could not promote the growth of E.
      coli (pUC19ECT)under high salinity.

PMID- 16579461
TI  - [Functional analyses of TcrA-a TPR-containing regulatory protein in Streptomyces
      coelicolor A3(2)].
AB  - In Streptomyces coelicolor A3(2), SCO5433 encodes a TPR domain containing protein
      designated TcrA (TPR containing regulator A). TcrA is similar in amino acid
      sequence to AfsR, a well-characterized global regulatory protein in S. coelicolor
      A3(2). Disruption of tcrA enhanced the production of spore pigment on MM
      containing glucose or mannitol and also resulted in more diffusible pigment
      production on MM containing mannitol or MS agar medium, but no significant
      effects on morphological differentiation were observed. Complementation of tcrA
      mutation restored the phenotype of tcrA mutant to that of the wild-type strain.
      These results suggest that tcrA is involved in the regulation of secondary
      metabolism under defined conditions. In S. coelicolor A3(2), the AfsK/AfsR system
      positively regulates the production of secondary metabolites while the results of
      our work suggest that there might be a TcrA-dependent pathway that negatively
      regulates secondary metabolism.

PMID- 16579462
TI  - [Construction of high sulphite-producing industrial strain of Saccharomyces
      cerevisiae].
AB  - In the process of beer storage and transportation, off-flavor can be produced for
      oxidation of beer. Sulphite is important for stabilizing the beer flavor because
      of its antioxidant activity. However, the low level of sulphite synthesized by
      the brewing yeast is not enough to stabilize beer flavor. Three enzymes involve
      sulphite biosynthesis in yeast. One of them, APS kinase (encoded by MET14) plays
      important role in the process of sulphite formation. In order to construct high
      sulphite-producing brewing yeast strain for beer production, MET14 gene was
      cloned and overexpressed in industrial strain of Saccharomyces cerevisiae. Primer
      1 (5'-TGTGAATTCCTGTACACCAATGGCTACT-3', EcoR I) and primer 2 (5'-TATAAGCTTGATGA
      GGTGGATGAAGACG-3', HindIII) were designed according to the MET14 sequence in
      GenBank. A 1.1kb DNA fragment containing the open reading frame and terminator of
      MET14 gene was amplified from Saccharomyces cerevisiae YSF-5 by PCR, and inserted
      into YEp352 to generate recombinant plasmid pMET14. To express MET14 gene
      properly in S. cerevisiae, the recombinant expression plasmids pPM with URA3 gene
      as the selection marker and pCPM with URA3 gene and copper resistance gene as the
      selection marker for yeast transformation were constructed. In plasmid pPM, the
      PGK1 promoter from plasmid pVC727 was fused with the MET14 gene from pMET14, and
      the expression cassette was inserted into the plasmid YEp352. The dominant
      selection marker, copper-resistance gene expression cassette CUP1-MTI was
      inserted in plasmid pPM to result in pCPM. Restriction enzyme analysis showed
      that plasmids pPM and pCPM were constructed correctly. The laboratory strain of
      S. cerevisiae YS58 with ura3, trp1, leu2, his4 auxotroph was transformed with
      plasmid pPM. Yeast transformants were screened on synthetic minimal medium (SD)
      containing leucine, histidine and tryptophan. The sulphite production of the
      transformants carrying pPM was 2 fold of that in the control strain YS58, which
      showed that the MET14 gene on plasmid pPM was expressed functionally in YS58. The
      industrial brewing yeast strain YSF-38 was transformed with the plasmid pCPM and
      yeast transformants were selected on YEPD medium containing 4mmol/L copper
      sulphate. The recombinant strain carrying pCPM showed a 3.2-fold increase in
      sulphite production when compared to the host strain YSF-38 under laboratory
      culture conditions. Flask fermentation under brewing-like conditions was
      performed in Tsingtao Beer Brewery. The sulphite production of the recombinant
      strain began to be higher than that of the host strain YSF-38 at the fourth day
      and reached the maximum at the eighth day. At the end of fermentation, the
      sulphite produced by recombinant strain is 1.4 fold of that in the host strain.
      The overexpression of MET14 gene in both laboratory and industrial strains of S.
      cerevisiae increases the sulphite formation. It is the first time to construct
      high sulphite-producing industrial strain by functional expression of MET14 in S.
      cerevisiae. Such study provides the foundation for construction of an excellent
      brewing yeast strain that can produce proper sulphite and can be used in
      commercial beer production.

PMID- 16579463
TI  - [Cloning and expression of arom gene of Sclerotinia sclerotiorum].
AB  - Arom gene, encoding a single polypeptide that catalyses steps two to six of the
      aromatic amino acid (phenylalanine, tyrosine and tryptophan) biosynthetic
      pathway, has been amplified from Scleortinia sclerotiorum genomic DNA by PCR and
      sequenced. In order to identify the fragment encoding AROM protein experimentally
      and search a method of obtaining the enzyme in a large amount, the open reading
      frame of arom gene of S. sclerotiorum was amplified by Pyrobest DNA Polymerase
      and inserted between Kpn I and Not I sites of the vector pYES2 to construct the
      expression vector pYES2-arom. The construct was transformed into Saccharomyces
      cerevisiae H158 by the method of LiAc/ SSDNA/PEG. The rate of transformation was
      2 x 10(2)/microg DNA, which was enough for the selection of the positive
      transformants. PCR using the extracted plasmids as the templates and restriction
      enzyme analysis of the plasmids extracted from E. coli cells transformed by the
      above plasmids were performed respectively to screen the positive S. cerevisiae
      transformants since the copy number of the plasmid in S. cerevisiae was low.
      Subsequently, the transformant activated by the SC-U medium containing 2%
      raffinose was inoculated into the SC-U medium containing 2% galactose and the SC
      U medium containing 2% glucose respectively to induce and depress the expression
      of the foreign arom gene. The results of RT-PCR analysis showed: there was not
      any DNA band in the negative control without the anti-transcriptase, which
      indicated there was no DNA contamination in the extracted total RNA; there was an
      expected DNA band in the positive control using the expression vector pYES2-arom
      as the template, which indicated the used amplification condition was proper;
      there was not any DNA band in the negative control using total RNA from the
      depressed transformant as the template, which indicated the DNA bands amplified
      from total RNA of the induced transformant were not false; there were the
      expected DNA bands in the samples using total RNA of the transformant induced for
      48h, 60h, 72h or 84h as the templates, which indicated the heterogeneous arom
      gene was transcribed in S. cerevisiae H158 cells. The result of Northern
      hybridization was consistent with that of RT-PCR, and showed that arom gene of S.
      sclerotiorum had been transcribed in S. cerevisiae H158 cells when the cells were
      induced for 48h in the SC-U medium containing 2% galactose at 30 degrees C at
      180r/min. 5-enolpyruvylshikimate-3-phosphate synthase activity of the
      transformant, which was one of AROM protein activities, was measured by
      estimating the rate of Pi release to check the expressed AROM protein was active
      or not. The results of enzyme assay in the different culture period indicated
      that the transformant had 5-enolpyruvylshikimate-3-phosphate synthase activity
      and the activity reached the peak when the transformant was induced for 72h in SC
      U medium at 30 degrees C at 180r/min. The molecular weight of AROM protein is
      high, it exists in cytoplasm as a dimmer and its expression is controlled by the
      amounts of amino acids. Therefore, it is very difficult to purify the enzyme. A
      great lot protein can be obtained by heterogeneous expression. S. cerevisiae
      expression system has the merits of safe status, authentic posttranslational
      modification, fast cultivation etc. and usually is the first choice eukaryotic
      expression system. S. cerevisiae expression system of AROM protein from S.
      sclerotiorum was successfully constructed for the first time, which provided the
      basis for the research on the catalysis mechanism of the enzyme and an economical
      means of simultaneously synthesizing five aromatic amino acid biosynthetic
      pathway enzymes.

PMID- 16579464
TI  - [Molecular mechanism affecting route of transmission for H9N2 subtype AIV].
AB  - The available evidence suggests that H9 subtype avian influenza virus (AIV) did
      not circulate in Chicken flocks in China until the early 1990s. However, the
      pandemic of H9 subtype AI, which started in summer of 1998, spread very rapidly
      to more than 20 provinces within several months. Obviously, the virus responsible
      for the 1998 pandemic was quite different from the virus isolated in early 1990s.
      In order to investigate the molecular mechanism affecting the route of
      transmission for H9N2 AIVs, strains of A/Chicken/Guangdong/SS/94 (H9N2) (SS) and
      A/Chicken/ Shanghai/F/98 (H9N2) (F) were compared in their route of transmission.
      SS strain representing the earlier strain was isolated in chickens in Guangdong
      province in 1994, whereas F strain was isolated in Shanghai during 1998 pandemic.
      The findings suggested that F strain could transmitted in chickens by direct
      contact and by aerosol route. Whereas SS strain only by direct contact, and
      neither of two viruses by fecal contact. The cDNAs derived from the HA and NA
      genes of SS strain were cloned into vector pHW2000 to construct two
      transcription/expression plasmids respectively, and the cDNAs derived from 8
      genes of F strain was done in the same way. Three recombinants were generated by
      reverse genetics: RF7/SSHA with the HA gene from SS strain and the remaining
      seven genes from F strain, RF7/SSNA with the NA gene from SS strain and the
      remaining seven genes from F strain, and RF7/SSHA/SSNA with the HA and NA genes
      of SS strain and the remaining six genes from F strain. In order to identify
      three recombinants, a total of seven genes from them were amplified by using PCR
      with universal primer pairs of H9N2 influenza virus and sequenced. In addition,
      three recombinants were characterized by HA and HI tests and sequence analysis.
      The results indicated that three recombinants were successfully rescued by
      reverse genetics. To determine the genes associated with the ability to transmit
      by aerosol route in chickens, a set of transmission experiments were designed.
      Groups of three chickens were inoculated with equal dose of virus by oral,
      intratracheal and intranasal routes. Each group was placed in direct, aerosol or
      fecal contact with three uninoculated chickens. Virus isolation and
      identification showed that only the RF7/SSHA recombinant was transmitted from
      inoculated to uninoculated chickens by aerosol route, whereas three recombinants
      were transmitted by direct contact, but not by fecal contact. The results were
      further confirmed by HI test of serum samples from uninoculated chickens. The
      data suggest that the NA gene might be the major determinant of the ability of
      aerosol transmission for H9N2 subtype AIVs in chickens.

PMID- 16579465
TI  - [Establishment of reverse genetics system for H5N1 subtype AI].
AB  - H5N1 subtype influenza virus A/Duck/Shandong/093/2004 (A/SD/04) strain was chosen
      as the master strain for rescue research. 11 sets of primers for 8 plasmids
      construction were designed base on the sequencing of the full-length of A/SD/04.
      Eleven fragments of A/SD/04 were amplified by the designed primers and were
      ligated with PHW2000 for rescue plasmid construction. Eight
      transcription/expression plasmids were obtained, which encoded the eight segments
      of A/SD/04, and designated as 241, 242, 243, 244, 245, 246, 247 and 248,
      respectively. The COS-1 cell was cotransfected with eight plasmids with different
      combination of A/SD/04 and PR8. The eight reassortants shared the same HA (from
      A/SD/04) but contained different internal genes and NA. All of the eight
      reassorted viruses had some similar bio-characteristics, such as the viral title
      in fertilized eggs was range from 256 to 1024, the EID50 were between 10(-8.5) to
      approximately 10(-9), and MDT were between 34 to approximately 46h. But the IVPI
      of the eight reassortants was differently and all were lower than the wild-type
      A/SD/04. These results confirmed that different recombination of internal genes
      of H5N1 has influence on viral virulence to 6-week SPF chicken but not on viral
      replication ability in embryonated chicken eggs. The establishment of eight
      plasmid rescue system for A/SD/04 is the base for farther research on genes
      function of H5N1. And A/SD/04 can be used as a backbone to replace PR8 entirely
      in generation of H5 AIV vaccine candidate.

PMID- 16579466
TI  - Bacterial expression and cellular localization of Helicoverpa armigera
      nucleopolyhedrovirus Orf33 in infected host cells.
AB  - Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus (HearSNPV) is a
      selective, highly infectious pathogen to H. armigera and has been extensively
      used for the control of this pest. This study presents the bacterial expression
      and localization of ha33 in infected host cells. The ha33 protein expressed in
      Escherichia coli had protein size of 17kDa. Western blot analysis using
      polyclonal antibody showed that the product of ha33 in infected Helicoverpa zea
      cells (HzAM1) was a 31kDa protein, larger than the theoretically predicted size
      of 28.4kDa. The confocal laser scanning microscope observation demonstrated that
      ha33 gene product was localized in the cytoplasm of infected HzAM1 cells
      beginning at 6 h p. i. and remained throughout the infection.

PMID- 16579467
TI  - [Combination of growing culture transformation and resting cells transformation
      of Pseudomonas putida NA-1 for production of 6-hydroxynicotinic acid].
AB  - The current technology for microbial hydroxylation of nicotinic acid is a
      procedure of resting cells transformation. Here it was reported that non
      degradation of 6-hydroxynicotinic acid during hydroxylation of nicotinic acid by
      resting cells was due to existing of nicotinic acid in the transformation
      mixture, not the death of cells. Therefore it was attempted that the induced
      cultivation of Pseudomonas putida NA-1 for hydroxylation activity by nicotinic
      acid was used for accumulation of 6-hydroxynicotinic acid to establish a new
      technology, a combined technology of growing culture transformation and resting
      cells transformation. In the combination technology, when 1% of nicotinic acid
      was kept in cultivation medium by supplement of nicotinic acid at intervals
      during cultivation of Pseudomonas putida NA-1, the growing culture could
      consistently hydroxylate nicotinic acid without degradation of its product which
      was accumulated linearly in the cultivation medium with progress of cultivation;
      the resting cells obtained from cultivation broth after growing culture
      transformation still processed a very high hydroxylation activity and could be
      used to next resting transformation of nicotinic acid. By using of the combined
      technology, the inducer was saved and the production yield of 6-hydroxynicotinic
      acid increased above 65%.

PMID- 16579468
TI  - [Effects of high hydrostatic pressure on energy metabolism of Lactobacillus
      plantarum].
AB  - Effects of high hydrostatic pressure on energy metabolism were investigated with
      Lactobacillus plantarum ATCC8014 as the test microorganism in this work. An INT
      colorimetric method of oxidation-reduction was established to measure INT
      metabolic activity of deoxidization of L. plantarum ATCC8014 cells. The
      utilization of glucose and INT metabolic activity of deoxidization of the cells
      after HPP treatment were determined using colorimetric methods. The experimental
      results showed that survival counts of ATCC8014 cells on MRS agar medium and INT
      metabolic activity of deoxidization decreased significantly, and little changes
      of utilization of glucose took place with increasing pressure ranging from 150 to
      250 MPa for 15 min. Utilization of glucose also reduced evidently at high
      pressure ( > 300 MPa) for 15 min. Whereas survival cell counts on MRS agar medium
      were below the detection limit and INT metabolic activity of deoxidization of
      ATCC8014 was 0% after a 15-min pressure holding time at 400MPa, utilization of
      glucose of the cells retained 56.1% compared with that of untreated cells. In
      summary, it can be concluded that enzymes absorbing and transporting glucose in
      cellular membrane appear to have a high resistance to pressure, enzymes and
      biological regulating systems involved in glycolysis are more resistant to
      pressure than those in TCA (tricarboxylic acid cycle) system, TCA of ATCC8014 is
      more sensitive to pressure than glycolysis, and the decrease of INT metabolic
      activity of deoxidization is highly related to cell reduction during HHP, which
      provide some theoretical evidences for mechanisms of HHP sterilization.
      Inhibition of TCA metabolism is a very important cause of ATCC8014 inactivation
      by HHP. High hydrostatic pressure can be used as an effective tool to explore
      pathways of biological metabolism.

PMID- 16579469
TI  - [Cloning and expression of delta6-desaturase gene from Thamnidium elegans in
      Saccharomyces cerevisiae].
AB  - A 459 bp DNA fragment was amplified from Thamnidium elegans As3.2806 with
      degenerate oligonucleotides primers designed based on the sequences information
      from the conserved histidine-rich motifs II and near III of fungal delta6-fatty
      acid desaturases genes by RT-PCR and sequenced. Gene specific primers designed
      according to this partial sequence were used for the amplification of the 3'- and
      5'- end of this cDNA by RACE method, and sequence information coming from these
      two ends were used to design two GSPs to clone the 1504bp full-length cDNA.
      Sequence analysis showed this cDNA sequence had an open reading frame (ORF) of
      1377bp encoding 458 amino acids of 52.4kD. The deduced amino acid sequence of the
      ORF showed similarity to those of the above delta6-fatty acid desaturases which
      comprise the characteristics of membrane-bound desaturases, including three
      conserved histidine-rich boxes and hydropathy profile. A cytochrome b5-like
      domain was observed at the N-terminus. To elucidate the function of the protein,
      two specific primers corresponding to the nucleotide sequences of start and stop
      codons were used to amplify the coding sequence. The amplified cDNA TED6 was
      subcloned into the expression vector pYES2.0 to generate a recombinant plasmid
      pYTED6, which was subsequently transformed into Saccharomyces cerevisiae strain
      INVScl for heterologous expression by lithium acetate method. Grown to
      logarithmic phase at 30 degrees C, the transformed cells were supplemented with
      0.5 mmol/L Linoleic acid and induced by 2% galactose for a further 48 h of
      cultivation at 20 degrees C. Total fatty acids were extracted from the induced
      cell and subjected to methyl-esterification. The resultant fatty acid methyl
      esters (FAME) were analyzed by gas chromatography (GC). A novel peak
      corresponding to gamma-linolenic acid (GLA) methyl ester standards was detected
      with the same retention time, which was absent in the cell transformed with empty
      vector. The percentage of this new fatty acid to total fatty acids was 7.5%. Gas
      chromatography-mass spectrometry (GC-MS) analysis of this fatty acid methyl
      derivative demonstrated that the novel peak was GLA methyl ester. These results
      showed that the coding product of this sequence exhibited the activity of
      converting linoleic acid (LA) to gamma-linolenic (GLA), and indicated that amino
      acid sequence exhibited delta6-fatty acid desaturase activity.

PMID- 16579470
TI  - [Cloning, sequence analysis and expression of alanine racemase gene in
      Pseudomonas putida].
AB  - Two distinct alanine racemase genes from Pseudomonas putida 200 were cloned and
      sequenced. DadX encodes a peptide of 357 amino acids with a calculated molecular
      weight of 38.82kDa. The putative product of alr gene is a peptide of 409 amino
      acids with molecular weight of 44.182kDa. A homology comparison revealed
      identities of 96.64%, 71.99%, 44.88% and 47.37% of the DadX alanine racemase to
      those from P. putida KT2440, Pseudomonas aeruginosa, Salmonella typhimurium and
      Escherichia coli, respectively. The amino acids sequence deduced from alr gene
      showed the homologies of 94.38%, 22.89%, 25.72% and 26.44% to those from the
      microorganisms above, respectively. Two motifs believed essential to the enzyme
      activity are found both in DadX and Alr, such as pyridoxal-5'-phosphate binding
      site. Both dadX and alr were expressed in E. coli TG1. Neither alanine racemase
      activity or serine racemase activity was detected in the host strain. Only
      alanine racemase activity was found in E. coli TG1/pCTD. But both E. coli
      TG1/pCTA and TG1/pCBA exhibit activity toward L-alanine and L-serine.
      Transcription of alr gene in E. coli is independent from extraneous promoter, a
      result confirmed by the significant enzyme activity observed in the E. coli
      TG1/pCBA, which indicates the presence of a possible promoter upstream the
      structure gene.

PMID- 16579471
TI  - [Effects of helper protein P20 from Bacillus thuringiensis on Vip3A expression].
AB  - Insecticidal crystal proteins (ICPs) produced in Bacillus thuringiensis
      accumulate as crystalline inclusions that represent up to 30% of total dry weight
      the cell produces. The mechanisms of in vivo crystallization of these
      insecticidal proteins remain interests, yet unclear. A 20-kDa protein (P20), the
      product of the third open reading frame of cry11A operon in B. thuringiensis
      subsp. israelensis has been defined to be an important molecular chaperone
      (helper protein) for forming Cyt1A crystal and enhancing Cry11A expression. The
      novel vegetative insecticidal proteins (VIPs) are secreted outside the cell of B.
      thuringiensis during mid-logarithmic growth. VIP3A shows activity against many
      lepidopteran insect larvae in a different mechanism from that of ICPs. To
      investigate the influence of helper protein P20 on Vip3A production and its
      insecticidal activity, P20 was coexpressed with Vip3A protein in B. thuringiensis
      and the yields and insecticidal toxicity of Vip3A were also analyzed. The
      recombinant plasmid pHVP20 was constructed by inserting a 5.4kb foreign fragment
      containing both vip3A gene and p20 gene into the shuttle vector pHT3101. The
      plasmid pHPT3 only containing vip3A gene was used as control. pHVP20 and pHPT3
      were transformed into the B. thuringiensis acrystalliferous strain CryB not
      containing vip3A gene by electroporation. The obtained B. thuringiensis
      transformants were CryB(pHVP20) and CryB(pHPT3) respectively. Western blot showed
      that Vip3A protein reached its maximum yield after 48h of CryB (pHVP20) growth
      and remained high expression level during the sporulation. The maximum yield of
      Vip3A protein in CryB (pHVP20) was about 1.5 fold as compared with that in
      CryB(pHPT3) by the mean of ImageMaster VDS software. It is considered that P20
      might combine with the native Vip3A protein during the sporulation, stabilize
      Vip3A and protect Vip3A from unspecific full proteolysis. Bioassay showed that
      the cell pellets of CryB (pHVP20) and CryB(pHPT3) performed high insecticidal
      toxicity against the first instar larvae of Spodoptera litura. Their LC50s of
      were 48.79 microg/mL and 78.00 microg/mL respectively and were not significantly
      different. Cell supernatants of two strains containing small amounts of secreted
      Vip3A were not toxic to the tested insect. It suggests that p20 can enhance the
      expression of Vip3A, but not improve its insecticidal toxicity remarkably.

PMID- 16579472
TI  - [Cloning, sequence analysis and expression of N-acetylglutamate kinase gene in
      Corynebacterium crenatum].
AB  - N-Acetylglutamate kinase (EC 2.7.2.8;NAGK) genes from wild-type Corynebacterium
      crenatum AS 1.542 and a L-arginine-producing mutant C. crenatum 971.1 were cloned
      and sequenced. Analysis of argB sequences revealed that only one ORF existed,
      which used ATG as the initiation codon and coded a peptide of 317 amino acids
      with a calculated molecular weight of 33.6kDa. Only one nucleotide difference was
      found in the structure gene and the difference did not cause a change of amino
      acid by comparison of the gene sequences between the wild type C. crenatum AS
      1.542 and the mutant 971.1. The ORF sequence of argB from C. crenatum AS 1.542
      showed homologies of 99.89%, 76.62%, 37.94% to those from Corynebacterium
      glutamicum ATCC 13032, Corynebacterium efficient YS-314 and Escherichia coli k12.
      And the amino acid sequence deduced from ORF displayed homologies of 100%,
      78.55%, 25.25% to those from microorganisms above, respectively. An internal
      promoter was found in the upstream of the argB gene from C. crenatum. The argB
      gene from C. crenatum AS 1.542 was expressed both in C. crenatum AS 1.542 and
      971.1. The NAGK activity of transformed C. crenatum AS 1.542 was greatly
      increased by the induction of IPTG. The NAGK activity of transformed C. crenatum
      971.1 was almost twice as much as that of C. crenatum 971.1 under the same
      induction. The amplification of the NAGK activity yielded 25% increase of L
      arginine production in C. crenatum 971.1.

PMID- 16579474
TI  - [cDNA cloning and expression of thermostable chitinase from thermophilic fungus
      Thermomyces lanuginosus].
AB  - A chitinase-encoding gene from Thermomyces lanuginosus was cloned by Rapid
      Amplification of cDNA Ends (RACE) using degenerated oligonucleotide primers
      designed from N-terminal amino acid sequence and the conserved amino acid
      sequence. The cloned full-length cDNA named chit, 1500bp in size, contained an
      OFR with 442 amino acids. The gene chit has been registered in GenBank with
      accession number DQ092332. The alignment results of putative amino acids sequence
      showed the catalytic domain of chit was high homology with the catalytic domains
      of the other chitinases in family-18, contained 2 conserved motifs related with
      catalytic activity of chitinase. The recombinant plasmid was generated by
      inserting the ORF of mature protein Chit into expression vector pPIC9K, and
      transformed into Pichia pastoris GS115. The recombinant chitinase was secreted
      successfully with the expression level of 0.36mg/mL and its activity could reach
      to 2.261U/mL after methanol induction 6d. The recombinant chitinase exhibited
      optimum catalytic activity at pH 5.5 and 60 degrees C. The enzyme was stable at
      50 degrees C and the half life time at 65 degrees C was 40min.

PMID- 16579473
TI  - [Fermentation and purification of Echistatin fusion protein expressed in
      Escherichia coli].
AB  - Lots of studies of Echistatin (Ecs) have proved its wide use in many aspects.
      However, the low yield of Ecs has impeded the relative researches of the protein.
      To establish the high-level expression system of Ecs, the fermentation and
      purification process of Ecs fusion protein expressed in E. coli were optimized.
      The Ecs gene was introduced into vector pTXB1 and placed under the control of
      highly efficient T7 promoter system. The cloned Ecs gene was expressed in E. coli
      BL21 (DE3) as soluble form. The Ecs production and biomass accumulation were
      optimized by examining medium composition, point of induction and induction time
      in fed-batch fermentation. Biomass accumulation was greatly affected by medium
      gradient, reaching 50.3g/L in 2 x YT medium. Ecs production was found to increase
      to 35% of total protein with 75g/L biomass accumulation after induced for 4h.
      Purification of Ecs from supernatant of sonication was done using one-step
      chromatographic procedure with chitin affinity chromatography and DTF cleavage,
      resulting in yields of 28mg/L and > 90% purity. The bioactivity of purified Ecs
      was determined and the result showed that purified Ecs could inhibit the
      aggregation of platelet in vitro with similar bioactivity to wild Ecs. This
      optimized method is readily scaled up for the expression and purification of Ecs
      in sufficient quantities for further structural and biological studies and
      applications.

PMID- 16579475
TI  - [Screening, identification of the strain Fds-1 for microbial desulfurization
      specially and its use in diesel oil desulfurization].
AB  - A strain Fds-1, which can specially break the C-S bond of dibenzothiophene (DBT)
      and convert DBT into 2-hydrobenzophene (2-HBP), was screened out from soil soaked
      with crude oil and identified as Bacillus subtilis. Both Gibb's reaction and GC
      MS analysis proved that this bacterium could remove sulfur of DBT by "4S"
      pathway. The optimal temperature of desulfurization is 30 degrees C. At this
      temperature, Fds-1 could remove 0.5mmol/L organ sulfur of DBT in 72h, so it is
      suitable to decrease the sulfur content of diesel oil. The final product named 2
      HBP is a water-soluble compound. This research focused on the desulfurization
      methods of diesel oil using Fds-1 resting cells. The results showed Fds-1
      exhibited strong degradation capacity of DBT and alkyl-DBT in diesel oil.
      Experiments of two diesel oil samples for desulfurization proved that Fds-1 did
      not break the carbon-carbon backbone and the calorific value of diesel oil was
      reserved. Therefore strain Fds-1 is significant to deep biodesulfurisation
      comparing the hydro-desulfurization of diesel oil.

PMID- 16579476
TI  - [Recombinant fowlpox virus coexpressing HA and NA gene from subtype H5N1 of avian
      influenza virus and its protective efficacy].
AB  - The hemagglutinin (HA) and neuraminidase(NA)gene from subtype H5N1 avian
      influenza virus were directly inserted into the transferring vector pllS,
      resulting in the recombinant transferring vector p11SH5ANA. Then p11SH5ANA was
      transfected into the chicken embryo fibroblasts (CEF), which was pre-infected
      with wild type fowlpox virus, to generate the recombinant fowlpox virus
      coexpressing H5A and NA (rFPV-11SH5ANA). By selection of blue plaques on the CEF,
      rFPV-11SH5ANA was obtained and purified. Experiments on SPF chickens demonstrated
      that the HI antibody titers in chickens vaccinated with HA-NA coexpressed vaccine
      was higher than those with HA expressed monovalent vaccines, and all chickens
      receiving either rFPV-11SH5ANA or rFPV-11SH5A were completely protected from the
      virulent AIV(H5N1) challenge, while those receiving wt-FPV experienced 100%
      mortality. The results showed that the rFPV-11SH5ANA was a safe and highly
      efficient gene engineering vaccine candidate for preventing HPAI.

PMID- 16579477
TI  - [Detection for the antiviral activity and primary application of the chicken
      gamma interferon in yeast Pichia pastoris].
AB  - To obtain recombinant chicken interferon gamma (ChIFN-gamma) with natural
      antivirus bioactivity in yeast Pichia pastoris eukaryotic expression system, the
      cDNA of chicken interferon gamma mature protein was synthesized by reverse
      transcription-polymerase chain reaction (RT-PCR)from the total mRNA of the
      lymphocyte from chicken blood, which stimulated with Con A for 4 to approximately
      10 hours. The 493 bp nucleotide sequence of chicken interferon gamma mature
      protein was cloned into expression vector pPICZa-A, which had been cleaved
      between EcoR I and Xba I . After linearized by BstX I, the recombinant vector was
      transferred into yeast Pichia pastoris, strain X33. The recombinant strain was
      isolated and identified by polymerase chain reaction. After induced by methanol,
      the recombinant protein was examined by SDS-PAGE. The result of SDS-PAGE analysis
      in the concentrated fermentation supernatant showed that the molecular weight of
      the recombinant protein was approximate 16kDa, two recombinants were conformed to
      secrete chicken interferon gamma(16kDa). The classical experiment of detection
      for interferon activity (cell pathological Effect Inhibition Assay)and the
      preliminary result of therapy proved that the recombinant protein is of good
      antivirus activity. So far chicken interferon gamma had been expressed highly in
      E. coli, but it tend to form biologically inactive inclusion bodied combined with
      difficulties in refolding, so the recombinant chicken gamma interferon with
      natural antivirus bioactivity produced in yeast expression system is the best
      way, the recombinant interferon gamma have great practical value and application
      foreground.

PMID- 16579478
TI  - [Hepatitis E virus of different genotypes contains multiple-type antigenic
      epitopes].
AB  - Monoclonal antibodies (McAbs) were prepared against a recombinant protein p166Us
      derived from US-1 strain of hepatitis E virus (HEV). The immune reactivity of the
      McAbs to seven p166s derived from different genotypes and subtypes of HEV, which
      included p166Bur (genotype I a), p166Pak (genotype I b), p166Mor (genotype I c),
      p166Mex (genotype II), p166Us (genotype III), p166Nz (swine HEV, genotype III)
      and p166Chn (genotype IV), was tested by an indirect enzyme-linked immunosorbent
      assay (ELISA) and a Western blotting assay. The immunological relationship
      between the McAbs and native HEV particles or anti-HEV positive serum samples was
      analyzed by an antigen-competitive or antibody-competitive ELISA. Totally, six
      McAb-producible hybridoma cell lines, designated by the name of 4D3, 2E3, 11E11,
      12H5, 3A3 and 1F1 respectively, were cloned and obtained in this study. The McAb
      of 4D3 could react to all of the seven p166 recombinant proteins. This kind of
      reaction could be inhibited by each of 4 genotypes of native HEV particles or
      anti-HEV positive serum samples. The McAbs produced by 2E3, 11E11 and 12H5
      reacted to p166Us, p166Nz and p166Chn, but did not react to p166Bur, p166Pak,
      p166Mor and p166Mex. The reaction of McAb of 2E3, as an example of the McAbs of
      2E3, 11E11 and 12H5, could be only inhibited by genotype III and IV HEV or anti
      HEV positive serum. The McAb of 3A3 could bind to p166Us as well as p166Nz. The
      McAb produced by 1F1 was reactive to the p166Us only. However, neither of I , II
      , IV genotype HEV particles or antisera could inhibit both of their reactions to
      p166Us. The data as mentioned above suggested that there are multiple-type
      antigenic epitopes such as genotype I, II, III and IV common, III and IV common,
      and III specific epitopes within HEV ORF2 encoded p166 proteins of different
      genotypes and subtypes of HEV. Moreover, the antigenic epitopes on recombinant
      protein p166s and these on native HEV particles possess identical immunological
      characteristics.

PMID- 16579479
TI  - [Genetic diversity and phylogeny of soybean bradyrhizobia isolated from south and
      north region of China].
AB  - Studies on genetic diversity and phylogeny of soybean bradyrhizobia isolated from
      south and north region of China were investigated through 16S rRNA gene PCR RFLP,
      16S rRNA gene sequencing and 16S-23S rRNA IGS PCR RFLP assays. Results of 16S
      rRNA gene PCR RFLP and 16S rRNA gene sequencing analysis reveal that strains
      tested are ascribed into Bradyrhizobium japonicum and B. elkanii species. B.
      japonicum is the dominant species and accounts for 91% of strains tested, but B.
      elkanii just up to 9%, which shows poor genetic diversity. Results of 16S-23S
      rRNA IGS PCR RFLP assays reveal that strains belonged to B. japonicum can be
      divided into Group I and Group HIIat the 69 similarity. Group I consists of
      strains from northern China, and Group 1I consists of strains from southern
      China, which demonstrates geographical effect on genetic diversity of
      bradyrhzobia. Results of 16S-23S rRNA IGS PCR RFLP further reflects that strains
      of Group I and Group II are phylogenetically different with type or
      representative strains USDA6, USDA110 and USDA122 of B. japonicum.

PMID- 16579480
TI  - [Analysis of DNA homology and 16S rDNA sequence of rhizobia, a new phenotypic
      subgroup, isolated from Xizang Autonomous Region of China].
AB  - Based on the studies of numerical taxonomy, the seven rhizobial strains isolated
      from the root nodules of leguminous plants Trigonella spp. and Astragalus spp.
      growing in the Xizang Autonomous Region of China constituted a new phenotypic
      subgroup, where wide phenotypic and genotypic diversity among legume crops had
      been reported due to complex terrain and various climate. The new phenotypic
      subgroup were further identified to clarify its taxonomic position by DNA
      homology analysis and 16S rDNA gene sequencing. The mol% G + C ratio of the DNA
      among members of the new subgroup ranged from 59.5 to 63.3 mol% as determined by
      T (m) assay. The levels of DNA relatedness, determined by using the DNA liquid
      hybridization method, among the members of the new subgroup were between 74.3%
      and 92.3%, while level of DNA relatedness between the central strains XZ2-3 of
      the new subgroup and the type strains of known species of Rhizobium was less than
      47.4%. These results indicated that the new phenotypic subgroup is a DNA
      homological group different from described species of Rhizobium. Therefore, this
      new phenotypic subgroup was supposed to be a new species in the genus of
      Rhizobium since the strains in the same species generally exhibit levels of DNA
      homology ranging from 70 to 100%. A systematic identification method-16S rDNA
      gene sequence comparison was carried out to determine the phylogenetic
      relationships of the new subgroup with the described species of Rhizobium. The
      GenBank accession number for the 16S rDNA sequence of the central strain XZ2-3 of
      the new subgroup is DQ099745. The full-length 16S rDNA gene sequence were
      sequenced by chain terminator techniques and analyzed with PHYLIP. The
      phylogenetic trees were constructed by using the programs DRAWTREE. The
      phylogenetic analysis indicated that new subgroup occupy a independent sub-branch
      in phylogenetic tree. The sequence similarities between the center strain XZ2-3
      and the closest relatives, strain R. leguminosarum USDA2370T and R. etli CFN42T,
      were 96.55% and 96.62% respectively. Both the 16S rDNA sequence data and the DNA
      relatedness data suggested that the new phenotypic subgroup isolated from the
      root nodules of leguminous plants Trigonella spp. and Astragalus spp. obtained
      from the Xizang Autonomous Region of China represents a new rhizobial species in
      the genus of Rhizobium according to the minimal standards for the description of
      new genera and species of root-and stem-nodulating bacteria.

PMID- 16579481
TI  - [Screening of botulinum neurotoxin type A-binding peptides by phage display
      peptide library].
AB  - To seek effective inhibitor against BoNT/A, in this study, BoNT/A-binding
      peptides were screened from phage display peptide library using synthesized and
      identified mimicry peptides that contained antigenic epitopes as targets.
      According to the homology of the amino acid sequences of displayed peptides, most
      had same motifs respectively. ELISA assay confirmed that identified positive
      clones respectively against P4 and P5 could specifically bind BoNT/A. The mice
      assay showed the specific BoNT/A-binding peptides could partially protect against
      challenge of BoNT/A. The results from the study may aid in the future
      identification of more potent small molecule inhibitors against BoNT/A.

PMID- 16579482
TI  - [Purification and properties of Citrobacter freundii phytase].
AB  - Phytase (myo-inositol-1,2,3,4,5,6-hexakisphosphate phosphohydrolase, EC 3.1.3.26)
      catalyses the stepwise hydrolysis of phytic acid (myo-inositol hexakisphosphate).
      Phytases are of great commercial importance due to their usage as supplement of
      food and animal feed, which can cater to nutrition demands and alleviate
      environmental problems, has been approved by many countries. Although acid
      phytases have been extensively studied, information regarding the phytases from
      Citrobacter is limited. In the work presented, a phytase was separated from
      Citrobacter freundii. After steps of electrophoretic homogeneity by successive
      ammonium sulfate between 60% and 80% saturation precipitation, DEAE-Sepharose ion
      exchange chromatography and gel filtration through Superdex HR 10/30, final gel
      elution resulted in a 41.3-fold purification and yield of 9.3%. Gel elution is an
      effective method to purify the protein which contaminated with a few other
      proteins. The purified preparations were used in subsequent characterization
      studies. Based on SDS-PAGE analysis, the molecular weight of the purified phytase
      was calculated to be approximately 45.0kDa in monomeric form. The pure enzyme has
      an optimum pH of 4.0 to approximately 4.5. It was found stable between pH5.0 to
      approximately 7.0, about 90% of the enzyme activity was retained at 37 degrees C
      for 60min. The phytase has an optimum temperature of 40 degrees C which was lower
      than that of other phytases from Aspergillus or E. coli (average 50 to
      approximately 60 degrees C) and was close to the temperature of gastrointestinal
      tract in animals (37 to approximately 40 degrees C). Thus the enzyme is a
      promising candidate for animal feed applications. Activity of the purified
      phytase was influenced by changing the reaction temperature. Data showed that the
      enzyme retained its activity over a long period when stored at 4 degrees C,
      whereas thermal inactivation studies indicated that the enzyme lost 100% activity
      after treatment at 60 degrees C for 4min. The Km values of the phytase for
      dodecasodium phytate at 37 degrees C was 0.85nmol/L with a Vmax 0.53IU/(mg x
      min). Phytase activity was strongly inhibited by SDS, Zn2+ and moderately
      inhibited by Cu2+, Cr3+, Fe2+ and Fe3+. Activity was not significantly affected
      by EDTA, K+, Mg2+ and Ca2+. The phytase has excellent resistance to trypsin, but
      not pepsin. The N-terminal amino acids sequence of the phytase protein was
      determined as QCAPEGYQLQQVLMM which exhibited about 80% homology to Glucose-1
      phosphatases from E. coli, Shigella flexneri and Salmonella, whereas it did not
      show apparent sequence similarity with any other phytase listed in the databases.
      Initial characterization of the purified enzyme suggested that it is a potential
      candidate for use as an animal feed supplement.

PMID- 16579483
TI  - [Purification and characterization of a cellobiohydrolase from the thermophilic
      fungus Chaetomium thermophilus CT2].
AB  - Chaetomium thermophilus CT2 was a cellulolytic fungus. It was a widely-existing
      saprophyte, which grower rapidly in soil. The cellulases synthesized by C.
      thermophilus CT2 was overall, consisting of three principal types of enzymes. The
      cellobiohydrolase was one of these three cellulases, which was associated with
      the endo-beta-1,4-glucanase and beta-glucosidase activities. C. thermophilus CT2
      produced cellobiohydrolase available at 50 degrees C, when grown on ferment
      liquid substrate, containing 1% Avicel, 0.14% (NH4 )2SO4, 0.2% KH2PO4, 0.03% CaC2
      x 2H2O, 0.03% MnSO4 x 7H2O, 0.1% peptone, 0.05% yeast extract, 0.1% Tween 80 and
      trace element solution at 1mL/L, containing 18mmol/L FeSO4 x 7H2O, 6.6mmol/L
      MnSO4, 4.8mmol/L ZnSO4 x 7H2O and 15mmol/L COCl2. A cellobiohydrolase was
      purified to homogeneity by an inexpensive and straightforward method for
      extraction of the enzyme involving fractional ammonium sulphate precipitation,
      ion-exchange chromatography on DEAE-Sepharose Fast Flow, gel filtration on
      Sephacryl S-100 and ion-exchange chromatography on Q Sepharose Fast Flow. The
      molecular weight of the enzyme was estimated to be 66.3kDa by 12.5% SDS-PAGE and
      was to be 67.1kDa by gel filtration on Sephacryl S-100 respectively. Kinetic
      studies of the purified cellobiohydrolase of C. thermophilus CT2 showed that the
      Km for p-NPC (p-trophenylbeta-d-cellobioside) was 0.956mmol/L as determined from
      a Lineweaver-Bark plot. Optimum enzyme activity was at 65 degrees C and pH5.0. It
      was thermostable at 60 degrees C and remained 20% activity after 20min at 80
      degrees C. The half life time of the enzyme at 70 degrees C was 1h. It indicated
      that the cellobiohydrolase possessed of excellent acid stability and thermostable
      property. The properties of the cellobiohydrolase make it possible to be good
      material in scientific researches of protein thermostable mechanism and good
      model for designing and constructing a new type protein in industry. The enzyme
      may also provide instructive insight on the diversity and mechanism of cellulose
      degradation by C. thermophilus CT2. As a thermophilic fungus C. thermophilus CT2
      is an attractive potential source of cellulases. It indicates that C.
      thermophilus CT2 may be a new excellent industrialized fungus for producing
      cellulases through molecule biology means.

PMID- 16579484
TI  - [Sited-directed mutagenesis of hCu, Zn-SOD gene and its expression in
      Synechococcus sp. PCC7942].
AB  - The Cys111 genetic code of human copper/zinc superoxide dismutase (hCu, Zn-SOD)
      gene in the pESOD plamid was mutated into the Ala111 code with site-directed
      mutagenesis, and then the plamid pESODT111 which contained groESL promoter,
      mutated hCu, Zn-SOD gene, rbcS-polyA terminator and reporter gene (Kanr) was
      constructed and transduced into Synechococcus sp. PCC7942 with homologous
      recombination platform. The results of PCR and DNA sequence analysis showed that
      the target nucleotide had been genetically integrated into genome DNA of the host
      cell. SDS-PAGE, Western blot and Pyrogallol autoxidation assay confirmed that the
      transformant strains expressed the mutated hCu, Zn-SOD protein. And the level of
      the mutated hCu, Zn-SOD protein reached a value of 3.61% of the total soluble
      protein. Furthermore, the transformants still retained 95% activities of SOD
      after 30 minutes at 80 degrees C environment, it indicated that the mutated hCu,
      Zn-SOD protein could endure higher temperature than the natural one.

PMID- 16579485
TI  - [Tracking of the development of fecal bacterial community of diarrhea piglets by
      16S rDNA techniques].
AB  - PCR and denaturing gradient gel electrophoresis (DGGE) were used to track the
      development of fecal bacterial community of 5 diarrhea piglets. Clone libraries
      were created from complete 16S rDNA of 42-day fecal sample of piglet 1, 2 and 5.
      From the library, clones had their V6-V8 regions matched predominant bands on the
      DGGE gel were then sequenced and their 16S rDNAs subjected to an online
      similarity search. Results revealed that DGGE profiles from fecal samples of 5
      piglets changed form simple to complex, and then returned simple to complex,
      finally tended to be stable and diverse. DGGE profiles from day 2and 16 fecal
      samples of 5 piglets were simplest, with high similarity (84%). Their most
      predominant bands were E. coil. Their Shannon index were 1.38 +/- 0.55 and 1.97
      +/- 0.26 respectively. DGGE profiles from day 10 of 5 piglets became quite
      complex, and had quite low similarity (10%) with DGGE profiles from day 2and 16
      fecal samples of 5 piglets. The Shannon index was 2.12 +/- 0.24. E. coil still
      existed, but it was not the most predominant band. There were significant
      differences of predominant bands between DGGE profiles from day 27 fecal samples
      and those from day 35 and 42 fecal samples, with 26.28% and 39.2% of similarity
      respectively. The predominant bands from day 35 and 42 fecal samples of 5 piglets
      were tended to be stable, with 55% of similarity. The Shannon index of day 27,
      day 35 and 42 fecal bacterial communities were 2.19 +/- 0.29, 2.20 +/- 0.17 and
      2.14 +/- 0.20 respectively. The fecal bacterial communities of day 42 health
      piglets were mainly consisted of species of Enterococcus, Streptococcus,
      Clostridium, Peptostreptococcus and Lactobacillus.

PMID- 16579486
TI  - [Glycine betaine supplied exogenously enhance salinity tolerance of Pseudomonas
      putida DLL-1].
AB  - The salinity tolerance characteristic of Pseudomonas putida DLL-1 and the
      environmental factors affecting the salinity tolerance of DLL-1 were
      investigated. The result showed that the enrichment of culture medium influenced
      the salt tolerance of DLL-1, in complete medium DLL-1 could survive higher
      salinities than in chemically defined medium. When inoculated to complete medium
      with 1mol/L NaCl, the least initial biomass guarantee DLL-1 surviving was
      1/100(V/V) of the medium volumes. But when inoculated to chemically defined
      medium with 1mol/L NaCl, the least initial biomass guarantee DLL-1 surviving was
      1/10(V/V) of the medium volumes. The effects of glycine betaine exogenously
      supplied on the salinity tolerance of DLL-1 and its osmo protection mechanisms
      were also studied. The results indicated that the glycine betaine present
      externally could promote the growth of DLL-1 under high salinity. 10mg/L of
      exogenous glycine betaine was sufficient to promote the growth condition of DLL-1
      cells under high salinities. 150mg/L glycine betaine could support DLL-1 cells
      grow in chemically defined medium with 1.2mol/L NaCl. The presence of glycine
      betaine in chemically defined medium could reduce significantly the lag time and
      generation time and increase the final biomass of DLL-1 under salt stress.
      Compared with the control without exogenous glycine betaine, the lag time of the
      treatment with exogenous glycine betaine could be reduced from 24h to 6h, and the
      generation time from 60min to 35.7min, the final OD610 value of culture increased
      from 1.29 to 1.57. Under osmotic stress, DLL-1 cells could synthesis glycine
      betaine, trehalose and free amino acid as the main compatible solute. When
      exogenously supplied, DLL-1 cells accumulated exogenous glycine betaine rapidly
      from medium to balance the extracellular osmolality instead of the synthesis of
      compatible solutes.

PMID- 16579487
TI  - [Construction of molecular clone of chimeric porcine circovirus(PCV1-2) and
      identification of its infectivity].
AB  - Porcine circovirus type 2(PCV2) recently emerged as an important infectious
      pathogen for pigs in the world. Unfortunately, there is no efficient method to
      deal with PCV2 infection until now. In this study, chimeric porcine circovirus
      molecular clone (pSK2PCV1-2) was constructed by cloning capsid gene of PCV2 into
      the backbone of PCV1. PK-15 cells was transfected with pSK2PCV1-2 and then
      cultivated in plate for five passages. mRNA of PCV1 ORF1 and PCV2 ORF2 were
      detected in the fifth passage, but mRNA of PCV1 ORF2 and PCV2 ORF1 were not
      detected in the cells. On the other hand, capsid protein of PCV2 was also
      detected in the nucleolus of transfected cells by IIF. This study indicated that
      pSK2PCV1-2 could form infectious virus in transfected cells. It will provide base
      for further study on biological characteristic of chimeric porcine circovirus.

PMID- 16579488
TI  - [An efficient method for DNA extraction from compost].
AB  - An efficient method for obtaining DNA from compost which contained high levels of
      organic matter was developed. The protocol consisted of washing with phosphate
      EDTA before extraction, cell lysis with hot-SDS and enzymes (lysozyme, lywalzyme,
      proteinase K), removing humic acid and other inhibitors with PVPP and
      precipitation with PEG-8000. The compost total DNA was extracted from four
      different composts, the DNA yield was 63.54 +/- 12.08 to approximately 106.50 +/-
      28.36 microg/g of dry compost. Molecular size of DNA obtained using this protocol
      was about 23kb and contained low protein and humic acid contamination with the
      A260/A280 ratios exceeding 1.6 and A260/A230 ratios reaching 1.8. Usually,
      additional purification steps such as agarose gel electrophoresis, gel permeation
      chromatography, or affinity chromatography were needed to get PCR-amplifiable
      DNA, but the DNA obtained using this protocol could directly be used to PCR
      amplification and restriction enzyme digestion. Just like purity of DNA template,
      lower DNA yield also appears to introduce a bias towards lower community
      diversity. In this study compared the purified DNA the direct DNA reveals higher
      microbial community diversity assessed by denaturing gradient gel
      electrophoresis(DGGE) of amplified V3 region of 16S rDNA.

PMID- 16579489
TI  - [Application of modern molecular biology techniques to study micro-ecosystem in
      the rumen].
AB  - The microbial community inhabiting in the rumen is characterized by its high
      population density, wide diversity and interactive complexity. However, until
      recently our knowledge of rumen microbiology was primarily based on classical
      culture based techniques (isolation, enumeration and nutritional
      characterization) which probably only account for 10% to 20% of the rumen
      microbial population. Modem molecular biology techniques provide effective
      methods to study the micro-ecosystem in the rumen. The use of molecular
      techniques based on nucleic acid probes is likely to revolutionize the approach
      to microbial ecology in the rumen and provide, not simply a refinement or
      increased understanding but a complete description of rumen community for the
      first time. Modem molecular techniques based on sequence comparisons of nucleic
      acids may be used to explore molecular characterization and provide a
      classification scheme which predicts natural evolutionary relationships. Genetic
      fingerprinting techniques that provide a pattern or profile of genetic diversity
      have been applied in a variety of environmental studies for the analysis of
      microbial communities. Whole-cell hybridization is a powerful technique which may
      be used to study the structure and function of microbial communities in situ and
      describe the expression of key enzymes. Real-time quantitative PCR technique may
      be conducted to accurately quantify the target microorganisms in the rumen.
      Development of these procedures and techniques will result in greater insights
      into community structure and activity of rumen microbial communities in relation
      to functional interactions, spatial and temporal relationships between different
      microorganisms and between microorganisms and feed particles. The successful
      development and application of these methods promise to provide the first
      opportunity to link distribution and identity of rumen microbes in their natural
      environment with their genetic potential and in situ activities.

PMID- 16579490
TI  - Linear and nonlinear hearing aid fittings--1. Patterns of benefit.
AB  - We evaluated the benefits of fast-acting WDRC, slow-acting AVC, and linear
      reference fittings for speech intelligibility and reported disability, in a
      within-subject within-device masked crossover design on 50 listeners with SNHL.
      Five hearing aid fittings were implemented having two compression channels and
      seven frequency bands. Each listener sequentially experienced each fitting for a
      10-week period. Outcome measures included speech intelligibility under diverse
      conditions and self-reported disability. At a group level, each nonlinear fitting
      was superior to the linear references for benefits in listening comfort, listener
      satisfaction, reported intelligibility and speech intelligibility. Slow-acting
      AVC outperformed the fast-acting WDRC fittings for listening comfort, while for
      reported and measured speech intelligibility the converse was true. For listener
      satisfaction there were no group differences between the nonlinear fittings.
      Analysis in terms of fittings for individual listeners revealed subsets with
      definite divergences from the group data and hence a need for candidature
      criteria. There are systematic differences between the benefits of nonlinear and
      linear fittings, and also within nonlinear fittings with fast versus slow time
      constants. The patterns of benefit and individual optima depend on the domain of
      outcome being assessed.

PMID- 16579491
TI  - Linear and nonlinear hearing aid fittings--2. Patterns of candidature.
AB  - We studied candidature for linear, slow-acting AVC hearing aids, and fast-acting
      WDRC hearing aids in a within-subject within-device crossover design of 50
      listeners with SNHL. Candidature dimensions include HTLs, ULLs, spectro-temporal
      and masking abnormalities, cognitive capacity, and self-reports and acoustic
      measures of auditory ecology. Better performance with linear fittings is
      associated with flatter audiograms, wider dynamic range, and smaller differences
      in dynamic range between low and high frequencies, and also with more restricted
      auditory lifestyles. Better performance with all nonlinear fittings is associated
      with more sloping audiograms, more restricted dynamic ranges, greater differences
      in dynamic range between low and high frequencies, and more varied auditory
      lifestyles. Differential performance between WDRC and AVC fittings is associated
      with patterns of variation in auditory ecology (rapid versus slow changes) and
      cognitive (high versus low) capacity. Differential performance between WDRC in
      two channels, and a hybrid with WDRC in a low-frequency and AVC in a high
      frequency channel is associated with psychoacoustic tests of cochlear function
      (high susceptibility to spectral and temporal smearing, and high susceptibility
      to upward spread of masking respectively). Patterns of candidature include
      measures beyond auditory function in the domains of cognitive capacity and
      auditory ecology.

PMID- 16579492
TI  - Effects of bilateral versus unilateral hearing aid fitting on abilities measured
      by the Speech, Spatial, and Qualities of Hearing Scale (SSQ).
AB  - The Speech, Spatial and Qualities of Hearing Scale (Gatehouse & Noble, 2004) was
      applied to three independent clinical groups: 144 people prior to being fitted
      with amplification; 118 people with six months experience with unilateral
      amplification; and 42 people with six months experience with bilateral
      amplification. For traditional speech hearing contexts (one-on-one, in groups, in
      quiet, in noise) there was benefit with one aid, and no further benefit with two.
      By contrast, hearing speech in demanding contexts (divided or rapidly switching
      attention) showed benefit with one aid and further benefit with two. In the
      spatial domain, directional hearing showed some benefit with one hearing aid, and
      particular further benefit in distance and movement discrimination from fitting
      with two. There was some benefit from unilateral fitting for elements of the
      qualities domains (clarity, naturalness, recognisability, segregation of sounds),
      with no consistent sign of further benefit from two. Bilateral fitting added
      benefit with respect to listening effort. Two hearing aids offer advantage in
      demanding and dynamic contexts; these contexts are argued as significant in the
      maintenance of social competence and emotional wellbeing. The present results go
      toward establishing the real-world advantages of bilateral hearing aid fitting
      and suggest that previous, inconclusive clinical findings reflect inquiry limited
      to more traditional areas of hearing function.

PMID- 16579493
TI  - Potential benefits of across-aid communication for bilaterally aided people:
      listening in a car.
AB  - We explored whether transferring signals between two hearing aids could improve
      speech intelligibility in noise. This was evaluated using a simulated
      conversation in a car; speech was presented to the right ear and car noise was
      presented either to the right or both ears. In three cross-aid communication
      conditions, the noise in the right ear was scaled and subtracted from the noise
      in the left ear. Speech intelligibility was determined for a group of normally
      hearing listeners and a group with bilateral hearing loss. The hearing-impaired
      group had relatively higher intelligibility scores when the car noise was diotic,
      whereas the normal-hearing group had relatively higher intelligibility scores in
      the binaural (dichotic) conditions. The cross-aid conditions led to improved
      intelligibility compared to the reference conditions. The results indicate that
      the transfer of signals between hearing aids may be of benefit when listening to
      speech in a car.

PMID- 16579494
TI  - Directional hearing aid benefit in listeners with severe hearing loss.
AB  - The purpose of this investigation was to examine the potential for directional
      hearing aid benefit in listeners with severe hearing loss at multiple SNRs for
      both auditory only and audio-visual presentation modes. Speech recognition
      performance was measured using the connected speech test at six SNRs individually
      determined for each subject in order to avoid floor and ceiling effects. The
      results revealed significant directional benefit was present at all tested SNRs
      in the presence of visual information. For auditory only presentations,
      significant directional benefit was only present at the least positive SNR. The
      largest directional benefit was measured at the poorest tested SNR for both
      auditory only and audiovisual presentation modes. The results of this study
      generally support small but significant directional for listeners with severe
      hearing loss benefit in a difficult listening environment both with and without
      the presence of visual information.

PMID- 16579495
TI  - The politics of fat.

PMID- 16579496
TI  - Mind over medicine.

PMID- 16579497
TI  - The multitasking generation.

PMID- 16579498
TI  - Sleeping-pill puzzler.

PMID- 16579499
TI  - The "foundations" of change.

PMID- 16579500
TI  - The reality of pain.

PMID- 16579501
TI  - Relationship between periodontal disease and systemic diseases.

PMID- 16579502
TI  - Pathophysiology of migraine: implications to patient care.

PMID- 16579503
TI  - Cortical spreading depression of migraine: overview and clinical implications.

PMID- 16579504
TI  - Migraine variants.

PMID- 16579505
TI  - Menstrual migraine.

PMID- 16579506
TI  - Migraine drug therapy: dental implications.
AB  - Triptan drugs continue to constitute the major pharmacotherapeutic interventional
      agents for migraine therapy. Interactions of dental drugs with migraine
      medications are limited, but their seriousness dictates that dentists be aware of
      the use of ergot alkaloids, triptans, or other migraine drugs. While many
      migraine sufferers avoid dental therapy dur ing migraine attacks, the
      practitioner who is treating a patient who has taken migraine medications must
      carefully monitor the cardiovascular status of the patient, which may affect the
      use of vasoconstrictors. Macrolide antibiotics and azole antifungals represent
      additional drug groups that are prescribed by dentists but which may potentiate
      the adverse effects of migraine drugs. Migraine patients prefer agents that offer
      rapid onset of relief and total relief within a couple hours of drug
      administration; they also prefer therapy that prevents recurrences and does not
      require "rescue" medications, and, of course, a lack of adverse effects and
      interactions with other medications. Currently, no single drug or class of drugs
      offers this ideal combination of actions in all patients.

PMID- 16579508
TI  - The business of dentistry success at every stage.

PMID- 16579507
TI  - The new 2005 American Heart Association Guidelines for Basic Life Support: a
      preview.

PMID- 16579510
TI  - Oral and maxillofacial pathology: Case of the month. Lichen planus.

PMID- 16579509
TI  - Sending medical waste via mail: can it reduce your disposal costs?

PMID- 16579511
TI  - [Patricio Zapata Ormeno, biography of a master].

PMID- 16579512
TI  - How the carotid body works: different strategies and preparations to solve
      different problems.
AB  - This is a review of the different experimental approaches developed to solve the
      problems in our progress towards a comprehensive understanding of how arterial
      chemoreceptors operate. An analysis is performed oi the bases, advantages and
      limits of the following preparations: studies of ventilatory reflexes originated
      from carotid bodies (CBs) in the entire animal; recordings of CB chemosensory
      discharges in situ; CB preparations perfused in situ; CB explants in oculo; CB
      explants in ovo; CB preparations incubated in vitro; CB preparations superfused
      in vitro; CB preparations perfused and superfused in vitro: CB tissue slices in
      vitro; cells acutely dissociated from CBs; CB cells in tissue culture; petrosal
      ganglia superfused in vitro; petrosal ganglion cells in tissue culture; and co
      cultures of CB and sensory ganglion cells. A brief historical account is given of
      the passage from one preparation to the next one. Emphasis is placed on personal
      experience with the different preparations whenever possible. Examples are given
      of the importance of selecting the appropriate experimental preparation for
      solving each particular theoretical problem. In fact, brilliant ideas on how the
      CB works have been unproductive until finding the adequate experimental approach
      to explore the validity of such ideas.

PMID- 16579513
TI  - Electrophysiological properties of rat nodose ganglion neurons co-transplanted
      with carotid bodies into the chick chorioallantoic membrane.
AB  - The electrophysiological properties of nodose ganglion neurons were evaluated
      immediately after removing nodose ganglia from young adult rats and 3 to 10 days
      after nodose ganglia implantation -either alone or co-implanted with carotid
      bodies- onto the chick chorioallantoic membrane. Implanted and co-implanted
      nodose neurons were less excitable than acutely recorded nodose neurons. Co
      implanted neurons also showed reduced amplitudes for both action potentials and
      spike after-hyperpolarizations relative to those found in. acutely recorded
      nodose ganglion neurons and a smaller time constant (T) than that found in
      implanted neurons. In addition, no spontaneous activity was recorded from nodose
      ganglion neurons co-implanted with carotid bodies during 3-9 days, which suggests
      that functional synapses between carotid glomus cells and nodose neurons were not
      yet established. Results indicate the feasibility of obtaining viable nodose
      neurons for up to 10 days grafted onto the chick chorioallantoic membrane, where
      they can conserve most of their passive and active membrane properties and also
      are susceptible to carotid bodies trophic influences. They also suggest that
      nodose neurons would need more time for the development of functional synapses
      when grafted with carotid body glomus cells.

PMID- 16579514
TI  - Cardiovascular and ventilatory acclimatization induced by chronic intermittent
      hypoxia: a role for the carotid body in the pathophysiology of sleep apnea.
AB  - Patients with obstructive sleep apnea (OSA) show augmented ventilatory,
      sympathetic and cardiovascular responses to hypoxia. The facilitatory effect of
      chronic intermittent hypoxia (CIH) on the hypoxic ventilatory response has been
      attributed to a potentiation of the carotid body (CB) chemosensory response to
      hypoxia. However, it is a matter of debate whether the effects induced by CIH on
      ventilatory responses to hypoxia are due to an enhanced CB activity. Recently, we
      studied the effects of short cyclic hypoxic episodes on cat cardiorespiratory
      reflexes, heart rate variability, and CB chemosensory activity. Cats were exposed
      to cyclic hypoxic episodes repeated during 8 hours for 4 days. Our results showed
      that CIH selectively enhanced ventilatory and carotid chemosensory responses to
      acute hypoxia. Exposure to CIH did not increase basal arterial pressure, heart
      rate, or their changes induced by acute hypoxia. However, the spectral analysis
      of heart rate variability of CIH cats showed a marked increase of the low/high
      frequency ratio and an increased variability in the low frequency band of heart
      rate variability, similar to what is observed in OSA patients. Thus, it is likely
      that the enhanced CB reactivity to hypoxia may contribute to the augmented
      ventilatory response to hypoxia.

PMID- 16579515
TI  - Chemical and electric transmission in the carotid body chemoreceptor complex.
AB  - Carotid body chemoreceptors are complex secondary receptors. There are chemical
      and electric connections between glomus cells (GC/GC) and between glomus cells
      and carotid nerve endings (GC/NE). Chemical secretion of glomus cells is
      accompanied by GC/GC uncoupling. Chemical GC/NE transmission is facilitated by
      concomitant electric coupling. Chronic hypoxia reduces GC/GC coupling but
      increases G/NE coupling. Therefore, carotid body chemoreceptors use chemical and
      electric transmission mechanisms to trigger and change the sensory discharge in
      the carotid nerve.

PMID- 16579516
TI  - Central actions of somatostatin in the generation and control of breathing.
AB  - The neuropeptide somatostatin is involved in many functions in the central
      nervous system as well as in the periphery. When it is centrally injected, an
      irreversible apnea is often developed. In the present review, we discuss the
      effects of somatostatin as the result of its actions at three levels of the
      respiratory neural network: a) by modulating the output of cranial or spinal
      motoneurons; b) by altering the genesis of the respiratory rhythm in the
      brainstem: and c) by regulating the chemosensory drive input into the respiratory
      pattern generator.

PMID- 16579517
TI  - Effect of 0.25 ppm ozone exposure on pulmonary damage induced by bleomycin.
AB  - To study the effect of ozone in a chronically damaged lung, we used a bleomycin
      (BLM) induced pulmonary fibrosis model. Both endotracheal instillation of BLM and
      O3 exposure both produce lung inflammation and fibrosis. Oxidative stress would
      be a common mechanism of damage for both BLM and O3. Our aim was to assess lung
      injury induced by 5 and 60 days of intermittent exposure to 0.25 ppm O3 in rats
      with bleomycin-induced pulmonary fibrosis. Thirty-day-old Sprague Dawley rats
      were endotracheally instilled with BLM (1 U/100 g body weight) and, 30 days
      later, exposed to 0.25 ppm 03 (0.25 ppm 4 h per day, 5 days a week).
      Histopatology controls were instilled with saline and breathing room air.
      Histopathological evaluation of lungs was done 5 and 60 days after O3 exposure.
      BLM-induced lung damage did not change after 60 days of intermittent O3 exposure.
      Five days of O3 exposure increased the mean score of BLM-induced pulmonary
      inflammation and fibrosis (p=0.06). Frequency of bronchopneumonia increased from
      1/7 to 6/6 (p <0.001), suggesting that a short-term exposure to O3 in a
      previously damaged lung might be a risk factor for developing further lung
      injury.

PMID- 16579518
TI  - The 'whole-animal approach' as a heuristic principle in neuroscience research.
AB  - Neuroscience embraces a heterogeneous group of disciplines. A conceptual
      framework that allows a better articulation of these different theoretical and
      experimental perspectives is needed. A 'whole-animal approach is proposed as a
      theoretical and hermeneutic tool. To illustrate the potential of this point of
      view, an overview of the research that has been performed in the extinction of
      fear-conditioned responses from Pavlov to the present is discussed. This is an
      example of how a whole-animal-based approach may help to organize and integrate
      basic and clinical neuroscience research. Our proposal is in agreement with
      recent statements calling for more integrative approaches in biological and
      neuropsychiatric research.

PMID- 16579519
TI  - Local regulation of the axonal phenotype, a case of merotrophism.
AB  - In this essay, we show that several anatomical features of the axon, namely,
      microtubular content, caliber and extension of sprouts, correlate on a local
      basis with the particular condition of the glial cell, i.e., the anatomy of axons
      is dynamic, although it is seen usually in its 'normal' state. The occurrence of
      ribosomes and messenger RNAs in the axon suggests that axoplasmic proteins are
      most likely synthesized locally, at variance with the accepted notion that they
      are supplied by the cell body. We propose that the supporting cell
      (oligodendrocyte or Schwann cell) regulates the axonal phenotype by fine-tuning
      the ongoing axonal protein synthesis.

PMID- 16579520
TI  - Cell surface and gene expression regulation molecules in dystrophinopathy: mdx
      vs. Duchenne.
AB  - Duchenne muscular dystrophy (DMD) is secondary to loss-of-function mutations in
      the dystrophin gene. The causes underlying the progression of DMD, differential
      muscle involvement, and the discrepancies in phenotypes among species with the
      same genetic defect are not understood. The mdx mouse, an animal model with
      dystrophin mutation, has a milder phenotype. This article reviews the available
      information on expression of signaling-related molecules in DMD and mdx.
      Extracellular matrix proteoglycans, growth factors, integrins, caveolin-3, and
      neuronal nitric oxide synthase expression do not show significant differences.
      Calcineurin is inconsistently activated in mdx. which is associated with lack of
      cardiomyopathy, compared to the permanent calcineurin activation in mdx/utrophin
      null mice that have a DMD-like cardiomyopathy. Levels of focal adhesion kinase
      (FAK) and extracellular regulated kinases (ERKs) differ among mdx and DMD.
      Further work is needed to identify the point of discrepancy in these signaling
      molecules' pathways in dystrophynopathies.

PMID- 16579521
TI  - Oligodendrocytes damage in Alzheimer's disease: beta amyloid toxicity and
      inflammation.
AB  - Research on Alzheimer's disease (AD) focuses mainly on neuronal death and
      synaptic impairment induced by beta-Amyloid peptide (Abeta), events at least
      partially mediated by astrocyte and microglia activation. However, substantial
      white matter damage and its consequences on brain function warrant the study of
      oligodendrocytes participation in the pathogenesis and progression of AD. Here,
      we analyze reports on oligodendrocytes' compromise in AD and discuss some
      experimental data indicative of Abeta toxicity in culture. We observed that 1
      microM of fibrilogenic Abeta peptide damages oligodendrocytes in vitro: while pro
      inflammatory molecules (1 microg/ ml LPS + 1 ng/ml IFNgamma) or the presence of
      astrocytes reduced the Abeta-induced damage. This agrees with our previous
      results showing an astrocyte-mediated protective effect over Abeta-induced damage
      on hippocampal cells and modulation of the activation of microglial cells in
      culture. Oligodendrocytes protection by astrocytes could be, either by reduction
      of Abeta fibrilogenesis/deposition or prevention of oxidative damage. Likewise,
      the decrease of Abeta-induced damage by proinflammatory molecules could reflect
      the production of trophic factors by activated oligodendrocytes and/or a
      metabolic activation as observed during myelination. Considering the association
      of inflammation with neurodegenerative diseases. oligodendrocytes impairment in
      AD patients could potentiate cell damage under pathological conditions.

PMID- 16579522
TI  - [Neuroendocrine system development during human ontogenesis].

PMID- 16579524
TI  - [The brain is a source of l-dihydroxyphenylalanine in fetus and newborn rats].

PMID- 16579523
TI  - [Analogs of anabasine as reversible and irreversible inhibitors of choline
      esterases of different animals].

PMID- 16579525
TI  - [Carbohydrates content og different region of gastrointestinal tract of reindeer
      Rangifer Tarandus during winter period].

PMID- 16579526
TI  - [Specific adaptive behavior of mangrove mollusks of Guinea seashore].

PMID- 16579527
TI  - [Mollusk Lymnaea Stagnalis locomotor activity during feeding., the role of pH of
      hemolymph].

PMID- 16579528
TI  - [Crayfish heart activity in awake, rest and "animal" hypnosis].

PMID- 16579529
TI  - [Compensatory mechanisms of Crayfish cardiovascular system in conditions of
      progressive hypoxia].

PMID- 16579530
TI  - [Functional characteristics of rat tracheal and bronchial smooth muscle at
      different stages of alveolitis].

PMID- 16579532
TI  - [Structural analysis of associative chains in teenagers with antisocial
      behavior].

PMID- 16579531
TI  - [Oxygen consumption in rat brain tissues in conditions of acute nitrite
      methemoglobinemia].

PMID- 16579533
TI  - [Confocal microscopy study of rotifera muscles anatomy].

PMID- 16579534
TI  - [NO-synthase involvement in regulation of vasopressinergic neurons of rat
      hypothalamus during early stages of postnatal development].

PMID- 16579535
TI  - [Age related sensitivity of honeybee glutamate receptors to agonists].

PMID- 16579536
TI  - [Macroglobulin protein family evolution].

PMID- 16579537
TI  - [Elimination of chromosome aberrations in lymphocyte cultures of the peripheral
      blood in people at remote time after acute irradiation].
AB  - The changes in registered levels of chromosome aberrations are studied in the
      peripheral blood lymphocyte cultures of patients irradiated in result of
      Chernobyl accident. All 71 patients were examined with a different frequency for
      different survival patients. The initial evaluations of the doses for them by the
      average frequency of dicentrics were realized at the nearest terms after the
      irradiation (from 0.2 before 9.8 Gy for different patients). Repeated blood
      samples were collected during 6 years after the accident. On the whole the model
      of exponential type Y(T)/Y(0) = c + exp(b(0) + b(1)T), where Y(T)--the frequency
      dicentrics at the time of examinations; Y(0)--the originally discovered dicentric
      frequencies; T--the time past after irradiation (days) was the most adequate for
      the quantitative description of the elimination of cytogenetical indices
      associated with different types of unstable chromosome aberrations. Also as a
      result of this study high individual variability of the elimination rate of the
      chromosome aberrations and its dependence from the value of the originally
      evaluated dose were discovered.

PMID- 16579538
TI  - [Structural chromosome organisation and radiation-induced interchromosomal
      aberrations].
AB  - The quantitative prediction of the biological effects of radiation is one of the
      actual tasks of radiobiology. The experimental study may be impossible under
      certain conditions (low doses, complex radiation fields, etc). The development of
      theoretical tools is required to predict biological and medical consequence of
      the irradiation of cell and organism. The effect under the consideration in the
      present paper is chromosome aberrations (CA) induced by low and high LET
      radiation. One of the most uncertain factors in CA prediction is the impact of
      chromosomal and nuclear architecture. In the present study the quantitative
      evaluation of the mechanisms of CA induction are discussed in the framework of
      the biophysical modelling technique taking into account interphase chromosomes
      structure in the nucleus of living (human) cell. We show that the surface
      contacts mechanism of interchromosomal aberrations (interchange) formation does
      not explain the observed ratio of simple/complex interchanges induced by both low
      and high LET radiation. The chromatin structure repositioning following
      irradiation is proposed as a possible mechanism involved in the formation of the
      complex aberrations.

PMID- 16579539
TI  - [About the "double" radioprotecting mechanism of some sulfur-containing
      substances].
AB  - The hypothesis about the double-acting mechanism of some radioprotectors during
      the irradiation of the DNA solutions is expressed in literature: the water
      radicals interception and the formation up to the irradiation of the additional
      intermolecular bonds "protector-DNA" (stabilization of the double helix). The
      realization conditions of this hypothesis were obtained by the molecular
      mechanics methods and the free radical mechanism appearance of the intrastrand
      cross-links "protector-DNA" during the irradiation of the polymer is given.

PMID- 16579540
TI  - [The combained effects of the long-term gamma-irradiation and heavy metall ions
      on the haematopoietic system of rats].
AB  - The combiened effects of different dose rates (0.625 microGy/s - 1.1 mGy/s) of
      gamma-irradiation and of cuprum and of cadmium ions on the haematopoietic system
      of rats were studied. It was found that only low dose rates (0.625-10 microGy/s,
      summary doses 0.5-2.0 Gy) of gamma-irradiation yields in the increasing
      proliferative activity of bone marrow. The number of myelocariocytos in S-phase
      was increased at 1.5-1.8 times. In case of the treatment with both cadmium
      chloride and radiation the changes in proliferative activity of bone marrow are
      completely due to the radiation factor. Combination of cuprum acetate and
      ionizing radiation induce opposite effects providing formal normalization of the
      haematopoietic characteristic of bone marrow up to 3, 6 and 12 months after the
      end of the radiation and the chemical exposure of the animal.

PMID- 16579541
TI  - [Effect of chronic ionizing irradiation on the structural properties of the
      apical and mitochondrial membranes of small intestine enterocytes].
AB  - The different ways of the radiation-induced effect were revealed in the
      investigations of chronic ionizing radiation influence in total doses of 0.3, 0.6
      and 1.0 Gy (0.0072 Gy/day) on the structural properties of the apical and of the
      mitochondrial membranes of small intestine enterocytes. The modification of the
      physical properties of the membrane surface area, the decrease of the structural
      order of the lipid component and conformational changes of the proteins were
      shown to be specific for the apical membrane. The disturbance of the dynamic
      properties and topography of the internal mitochondria membrane was revealed in
      the investigation of the inductive-resonance energy transfer between the pairs of
      the fluorophores: tryptophan-pyrene, tryptophan-ANS, pyrene-ANS.

PMID- 16579542
TI  - [The inhibiting effect of a low-dose ionizing radiation on the primary humoral
      immunity in the early period of an postnatal ontogeny].
AB  - The single exposition of 3- and 4-week mice in a dose 0.1 Gy resulted in
      depressing primary T-dependent humoral immune response. Unlike juvenile ones at
      adult 16-week animals the stimulation antibody-formation took place. As a result
      of the administration of immunomodulating drugs, thymogene and nucleinate of a
      sodium in irradiation mice of 3-week age was an augmentation of the number of
      antibody-producing cells relatively in 2 and 4 times. At the same time at
      irradiated in dose 0.1 Gy of adult mice thymogene abrogated the stimulating
      effect of radiation. It is suggested that the probable cause of the
      immunosuppressing effect of a small dose of radiation can be an inactivation of a
      radiosensitive subpopulation of helper cells or selective stimulation of the
      functional activity of neonatal suppressor cells.

PMID- 16579543
TI  - [Effect of the spaceflight radiation factor on the growth of Brassica pekinensis
      and micromycetes Fusarium oxysporum].
AB  - The effects of chronic exposure in the combination of low-dose gamma- and neutron
      radiation on growth of Brassica pekinensis (lour) Rupr, var. Khibinskaya, and
      micromycetes of Fusarium oxysporum, a representative of soil microflora were
      stadied. Seeds, water and vegetating plants raised from previously irradiated
      seeds were subjected to radiation exposure. The gamma-neutron dose rate was 
      0.013 sGy/d and the neutron flux was -20 n/cm2 d. Growth of Brassica pekinensis
      and of Fusarium oxysporum on the background of weak chronic ionizing irradiation
      by radioactive nuclides was noticeably changed when compared with the growth in
      the normal radiation environment. The radiosensitivity of Fusarium oxysporum
      isolated from the artificial soil following 60-d exposure was far higher than the
      radioactivity of the culture isolated from non-irradiated soil. Fusarium
      oxysporum isolated from the irradiated soil failed to form spores normally even
      when cultivated in a non-irradiated nutrient substrate without further exposure.
      These peculiarities persisted at least for four months. 15-mo gamma- and neutron
      exposure of Brassica pekinensis seeds held in storage for 5 years retained their
      original germinating capacity, whereas the non-irradiated seeds suffered
      deprivation of this quality. It was noticed that the Brassica pekinensis reaction
      on chronic exposure of low doses was markedly dependent on the growth conditions
      non-related directly with the radiation background.

PMID- 16579544
TI  - [137Cs distribution and accumulation in organs and tissues of sheep in the event
      of chronic consumption of contaminated fodder in the area of the Chernobyl NPP
      accident].
AB  - The regularities of 137Cs distribution and accumulation in organs and tissues of
      sheep on a farm located in the Chernobyl accidental zone were experimentally
      estimated. The distribution pattern of 137Cs concentration in organs and tissues
      is found to depend on the duration of the radionuclide uptake with the ration.
      During the first 24 h the highest 137Cs concentration is reported in the
      parenchymal organs; starting from day 30 muscular tissue and kidneys rank first,
      whereas in the other organs and tissues 137Cs concentration is 1.5-2 times lower.
      By 137Cs content and accumulation rate the study organs are arranged in a
      declining order as follows: muscles > > skin > liver > kidneys > heart > spleen.
      The mathematical models were devised describing the dynamics of increasing with
      time in 137Cs concentration in muscles, liver and skin. The methodology is
      suggested for the prediction of levels of 137Cs contamination of the muscular
      tissue of sheep. The time periods were regulated for sheep feeding with 137Cs
      contaminated fodder that ensure the production of mutton the radionuclide
      concentration in which meets the sanitary-hygienic standards.

PMID- 16579546
TI  - [The accumulation of the technogenic radionuclides by mushrooms in the area
      affected by the activity of the Krasnoyarsk mining-and-chemical industrial
      complex].
AB  - The radionuclide content was measured in mushrooms collected in different sites
      situated in the zone of the radiation influence on the Mining-and-Chemical
      Combine at Zheleznogorsk and on the control site, near Krasnoyarsk, in 2002-2004.
      The analytical investigations of fruiting bodies of 12 mushroom species have
      revealed three gamma-emitting radionuclides: 7Be, 40K (natural) and 137Cs
      (artificial). It was found that only three species contain 7Be; activity
      concentration of 40K is not species- and site-dependent, averaging 1600 Bq/kg.
      All collected samples contain 137Cs, and its accumulation by mushrooms is species
      specific. Suillus concentrates more 137Cs activity than other species and can be
      used as a bioindicator of soil contamination with radiocesium. The average
      activity concentration of 137Cs in Suillus granulatus collected in the sites
      subjected only to aerosol discharges of the MCC is more than twice higher than
      137Cs content of the mushrooms collected in the control site--"Krasnoyarsk". The
      maximum activity concentration of 137Cs in Suillus samples collected in the sites
      that receive 137Cs with the flood water is an order of magnitude higher,
      amounting to 8624 Bq/kg. The analysis of the radionuclide distribution in a
      mushroom shows that 40K activity concentration is the same in caps and stems of
      Suillus, and 137Cs concentration in Suillus caps is 1.7-2.3 times higher than in
      stems. Binding of radionuclides by mushroom biomass was determined by chemical
      fractionation; it was found that the highest activities of 137Cs and 40K are in
      the exchange-adsorption fraction (56 to 71% of the total content of a
      radionuclide) and in the organic fraction (23 to 37%). Calculations were made for
      determination of the coefficients of 40K and 137Cs transfer from the soil to the
      fruiting body of Suillus.

PMID- 16579545
TI  - [The parameters of clearance of industrially significant alpha-emitters from the
      lungs of mammals].
AB  - Results of assessment of biokinetic parameters of change in the burden of
      significant alpha-emitters in the lungs of mammals in various times after
      inhalation intake (Qt(lung)) were generalized. 1740 Wistar rats of both sex with
      the initial age of 2-2.5 months and 143 mature mongrel dogs used in 23 and 3
      animal tests, respectively, were involved in this work. The analysis of
      experimental data resulted in selection of three groups of chemically soluble
      compounds of alpha-emitters that differ in the rate of radionuclide clearance
      from the lung as well as in integral doses. Stable complex compounds of
      quadrivalent and of hexavalent nuclides and non-complex salts of quinquivalent
      and of hexavalent 237Np were assigned to the group of soluble compounds of 239Pu
      and 237Np. A three-component exponential model of change in Qt(lung) with the
      prevalence of fast and of intermediate phases (55%, T(eff) = 0.41 days and 35%,
      T(eff) = 18.1 days respectively) and the presence of a slow clearance phase (10%,
      T(eff) = 206 days) was developed for these compounds. Complex compounds of
      quadrivalent 239Pu and 237Np unstable in the environment of pH and of body
      temperature, their non-complex salts of mineral acids in ionic or polymer form,
      and submicron plutonium dioxide (SMD = 0.07 mkm) were assigned to the group of
      relatively soluble compounds includes. An exponential model with 2-3 components
      with the prevalence of intermediate and of slow clearance phases (71%, T(eff) =
      19.3 days and 22%, T(eff) = 169 days respectively) was developed for compounds of
      this group. The third group of the compounds is presented based on the soluble
      241Am compounds that could be typical for stable trivalent compounds of rare
      earth and transuranium radionuclides. Their biokinetics is described by a 3-4
      component exponential model with the fast phase prevailing (96.7%, T(eff) < or =
      6.8 days), and with intermediate (2.6%, T(eff) = 69 days) and with slow (0.7%,
      T(eff) = 1040 days) phases being negligible. Physical chemicas and biological
      processes determining nuclides biokinetics in lungs are discussed.

PMID- 16579547
TI  - [Effect of the physiological-biochemical characteristics variability on a
      radiosensitiveness of the Atriplex patula L. and Artemisia vulgaris L. ecoforms].
AB  - On the example of the physiological and the cytology-biochemical characteristics
      variability of an Atriplex patula L. and Artemisia vulgaris L. sprouts which
      parental plants were generated in various environmental conditions (South
      Yakutia, the Central Yakutia, Middle Ural), was shown, that radiostability
      depends not only on set protective antioxidant, on the DNA-reparation systems and
      on the vulnerability degree of a functioning genome, but also on the phenotypic
      diversifications of a population which in turn, in the certain degree, are
      consequence of previous selection of a population to all set of ecological
      stresses-factors of the environment.

PMID- 16579549
TI  - [The deflation of the soils and the horizontal migration of 137Cs].
AB  - The results of the researching of 137Cs migration with deflation soils are
      presented. It was established, that on drained peat and on sod-podsolic sandy
      soils, subjected to the radioactive pollution, the deflation is a major factor of
      the horizontal carry radionuclides. The quantity indicators of the 137Cs
      migration depend on the density of the pollution of the top layer soils, on the
      intensity of deflationary processes and on the use of the agricultural grounds.
      At the identical density of the pollution on drained peat soils the 137Cs carry
      is higher on 25-35%, than on mineral easy ones. The decrease of the deflationary
      processes to maximum permissible levels (for the drained peat soils--0.2-0.5, for
      sandy soils--1.3 t/ha per one year) promotes the reduction of the 137Cs migration
      on drained peat soils on 92-94%, on sod-podsolic sandy soils--on 87%.

PMID- 16579548
TI  - [The transfer of 90Sr and of 137Cs radionuclides in the chain of soil-fodder
      animal products in the area contaminated as a consequence of the Chernobyl AES
      accident].
AB  - The database on 137Cs and or 90Sr transfer factors in the soil-fodder-animal
      products chain compiled in the framework of the project "Radioecological
      Consequences of the Chernobyl Accident" under the French-German Initiative was
      analyzed. The 137Cs transfer factors were determined into 10 fodder types for
      farm animals. The 137Cs and 90Sr transfer from daily diet to milk is practically
      independent from milk yield and season and is about 0.83% and 0.16%. 137Cs
      transfer factor into beef (adult animals) is about to 2.4% from the daily uptake
      with fodder per 1 kg meat.

PMID- 16579550
TI  - [The restoration of the enzyme activity of chernozem soil after gamma
      irradiation].
AB  - The Influence of gamma-radiation by dozes 1, 5, 10 and 20 kGy on enzyme activity
      of ordinary chemozem were studied. Dynamics of the restoration of the enzyme
      activity after the influence of gamma-radiation in model experiments in 3, 30, 90
      and 180 days was investigated. The doze 1 kGy did no statistically significant
      influence on the investigated enzymes. Dehydrogenase is more radiosensitive
      enzyme than catalase. Values of the saccharase activity differed a significant
      variation so in most cases it has not been registered statistically significant
      changes. In 90-180 days of the incubation enzymes activity was restored up to
      control values. Dehydrogenase activity in 180 days in variants with dozes 10 and
      20 kGy was restored up to a level of the control, over variants with dozes 1 and
      5 kGy--is higher than the control over 78% and 23% accordingly. Saccharase
      activity in 180 days after the influence of gamma-radiation with a doze 20 kGy
      was on 61% lower than the control.

PMID- 16579551
TI  - [The study of the multifactorial anthropogenic effect on the ecosystems of the
      industrial reservoirs of "Maiak" industrial complex].
AB  - The analysis of the ecological situation of the Southern Urals industrial water
      reservoirs of the nuclear fuel cycle enterprise, "Mayak" PA is represented. The
      study was held in the 80s - early 90s. The subjects of the study were: a cooling
      water reservoir--Kysyl-Tash Lake (R-2) as well as a radioactive waste storage
      reservoir (R-10). Irtyash Lake, which is a drinking water reservoir for the city
      of Ozyorsk and Alabuga and Kazhakul Lakes, located on the boundary of the Eastern
      Urals Radioactive Trace (EURT), were taken as control ones. Such water reservoirs
      as Irtyash, Kysyl-Tash and the waste storage reservoir (R-10) are incorporated
      into the Techa River basin; while Alabuga and Kazhakul Lakes are related to the
      interfluve between the Techa River and the Sinara River. The complex effect from
      such man--caused factors as radiation, chemical and thermal to water reservoirs'
      ecosystems was studied. Radionuclide specific activities of the major reservoir
      components (water, bottom sediments, and biological objects), cumulative stock
      and radiation doses to the biota were determined. Assessment of the condition of
      biological structures of individual reservoirs was performed. It was found that
      the long-term complex influence of radiation, thermal and chemical factors
      resulted in the formation of the unique technology-induced ecosystems being a
      part of "Mayak" PA process cycle. Radiation doses to the fish of the cooling
      water reservoir and the radioactive waste storage reservoir were experimentally
      estimated. These doses from the incorporated beta-emitters were not less then 2-3
      Gy/year. The long-term complex influence of radiation and chemical factors didn't
      cause any irreversible changes either in the fish population or in the ecosystem.
      Water purity indicators like crayfish (Astacus leptodactilus Esch) and mollusk
      (Anodonta cygnea L.) were found in the cooling water reservoir. The comparative
      analysis of the ecological situation of the reservoirs carried out on the basis
      of several qualitative indicators and with the help of the formalized scoring
      system allowed determining that the optimum ecological conditions can be observed
      in Irtyash Lake. The quality of the environment of Alabuga Lake is slightly
      lower. The ecological conditions in Kysyl-Tash Lake are up to the standard, while
      in Kazhakul Lake they are lower than the standard. This is the result of the
      natural salinization of the ecosystem. The lowest indicator was obtained for the
      radioactive waste storage reservoir.

PMID- 16579553
TI  - [The XXVIII Session of the General Assembly on the International Union of the
      Radioecology].

PMID- 16579554
TI  - [International Conferences "Radioactivity in Environment" and "Radioactivity in
      Arctic and Antarctic"].

PMID- 16579552
TI  - [Current radioecological conditions of Malyi Igish lake located on the axial part
      of the East-Urals radioactive trace].
AB  - The paper presents data on the current radioecological situation at Lake Maly
      Igish located on the axial part of the East-Urals radioactive trace formed after
      the 1957 accident at the Mayak PA. The chemical composition of the water and
      bottom deposits, as well as the distribution of 90Sr, 137Cs, and of the
      microelements in the main components of the water reservoir were studied. The
      current species composition of higher aquatic plants and of the species-specific
      concentration of 90Sr and of 137Cs was identified.

PMID- 16579555
TI  - [International Conference "Modern Problems of Genetics, Radiobiology,
      Radioecology, and Evolution].

PMID- 16579557
TI  - Transducing mechanical force by use of a diffraction grating sensor.
AB  - A novel means of transducing mechanical force by using a polymeric-based
      diffractive grating sensor is presented. The diffraction gratings are
      successfully fabricated upon poly(dimethyl siloxane) polymer substrates by
      holographic interference and micromolding. A micromaterial tensile test
      incorporated into the surface diffraction grating experiment showed that a
      relationship between the load and the observed diffraction-pattern shift could be
      obtained. The results show an excellent correlation between the optical
      measurement and load, with a sensitivity of 0.05 N.

PMID- 16579556
TI  - [III International Symposium "The Chronic Irradiation: Medical-Biological
      Effects"].

PMID- 16579558
TI  - Spatial-spectral modulating snapshot hyperspectral imager.
AB  - Experimental results are presented for a computed tomography imaging spectrometer
      (CTIS) with imposed spatial-spectral modulation on the image scene. This
      modulation structure on the CTIS tomographic dispersion created substantial gains
      in spectral reconstruction resolution after standard iterative, nonlinear,
      inversion techniques were used. Modulation limits system ambiguities, so high
      frequency spectral and low-frequency spatial scene data could be recovered. The
      results demonstrate how spatial modulation acts as a high-frequency spectral
      deconvolver for the snapshot hyperspectral imager technology.

PMID- 16579559
TI  - Phase retrieval in digital speckle pattern interferometry by application of two
      dimensional active contours called snakes.
AB  - We propose a novel approach to retrieving the phase map coded by a single closed
      fringe pattern in digital speckle pattern interferometry, which is based on the
      estimation of the local sign of the quadrature component. We obtain the estimate
      by calculating the local orientation of the fringes that have previously been
      denoised by a weighted smoothing spline method. We carry out the procedure of
      sign estimation by determining the local abrupt jumps of size pi in the
      orientation field of the fringes and by segmenting the regions defined by these
      jumps. The segmentation method is based on the application of two-dimensional
      active contours (snakes), with which one can also estimate absent jumps, i.e.,
      those that cannot be detected from the local orientation of the fringes. The
      performance of the proposed phase-retrieval technique is evaluated for synthetic
      and experimental fringes and compared with the results obtained with the spiral
      phase- and Fourier-transform methods.

PMID- 16579560
TI  - Axially resolved complete mueller matrix confocal microscopy.
AB  - We introduce a technique that is capable of obtaining complete polarization
      sensitive three-dimensional images that could reveal unknown anatomical
      conditions of living tissue that possess polarization-dependent signatures.
      Previously, the 16 Mueller coefficients were measured independently only by use
      of two-dimensional imaging techniques. We also present the experimental
      combination of a depth-resolved confocal imaging system with a complete Mueller
      matrix polarimeter. To calibrate the system, a double-pass method had to be
      implemented. We also indicate, experimentally, that the confocal sectioning of
      the system has a degrading effect on axially resolved Mueller matrix
      measurements.

PMID- 16579561
TI  - Infrared zone-scanning system.
AB  - Challenges encountered in designing an infrared viewing optical system that uses
      a small linear detector array based on a zone-scanning approach are discussed.
      Scanning is performed by a rotating refractive polygon prism with tilted facets,
      which, along with high-speed line scanning, makes the scanning gear as simple as
      possible. A method of calculation of a practical optical system to compensate for
      aberrations during prism rotation is described.

PMID- 16579563
TI  - Finite-difference time-domain analysis of frequency-selective surfaces in the mid
      infrared.
AB  - We use the finite-difference time-domain (FDTD) method to model the spectral
      properties of frequency-selective surfaces (FSSs) at normal incidence in the 1-10
      microm wavelength. At these wavelengths the usual assumption that the metallic
      portions of a FSS are infinitesimally thin perfect conductors are no longer
      valid. We include the effects of dispersive complex conductivity for real metals
      and dispersive permittivity for dielectric materials by developing a unified
      approach that is especially suited for use in FDTD simulations. We concentrate on
      the finite nature of the metallic conductivity and its variation with wavelength
      in FSS structures. Our simulation results indicate that the resonant spectrum of
      a FSS in this wavelength range depends not only on the geometry of the structure
      and the dielectric substrate present, but also critically on the dispersive
      properties of the metal species used for the conductors.

PMID- 16579562
TI  - Optical waveguide biosensors constructed with subwavelength gratings.
AB  - The reflection resonance spectrum of a subwavelength diffraction-grating-coupled
      waveguide is used to analyze biomolecular interactions in real time. By detecting
      this resonance wavelength shift, the optical waveguide biosensor provides the
      ability to identify the kinetics of the biomolecular interaction on an on-line
      basis without the need for extrinsic labeling of the biomolecules. A theoretical
      analysis of the subwavelength optical waveguide biosensor is performed. A
      biosensor with a narrow reflection resonance spectrum, and hence an enhanced
      detection resolution, is then designed and fabricated. Currently, the detection
      limit of the optical waveguide sensor is approximately 10(-5) refractive-index
      units. The biosensor is successfully applied to study of the dynamic response of
      an antibody interaction with protein G adsorbed on the sensing surface.

PMID- 16579564
TI  - Cancellation of bending-induced birefringence in single-mode fibers: application
      to faraday sensors.
AB  - We demonstrate that one can cancel the bending-induced linear birefringence in
      single-mode fibers by inducing a controlled anisotropy in a direction orthogonal
      to the bending plane. In particular, the controlled anisotropy can be generated
      by application of a lateral compressive stress on the fiber. This effect can be
      applied for the construction of birefringence-free fiber coils in Faraday sensor
      heads (e.g., in current sensors) to improve their sensitivity.

PMID- 16579565
TI  - Lithographic characterization of the spherical error in an extreme-ultraviolet
      optic by use of a programmable pupil-fill illuminator.
AB  - Extreme-ultraviolet (EUV) lithography remains a leading contender for use in the
      mass production of nanoelectronics at the 32 nm node. Great progress has been
      made in all areas of EUV lithography, including the crucial issue of fabrication
      of diffraction-limited optics. To gain an accurate understanding of the
      projection optic wavefront error in a completed lithography tool requires
      lithography-based aberration measurements; however, making such measurements in
      EUV systems can be challenging. We describe the quantitative lithographic
      measurement of spherical aberration in a 0.3 numerical aperture. EUV microfield
      optic. The measurement method is based on use of the unique properties of a
      programmable coherence illuminator. The results show the optic to have 1 nm rms
      spherical error, whereas interferometric measurements performed during the
      alignment of the optic indicated a spherical error of less than 0.1 nm rms.

PMID- 16579566
TI  - High-resolution angle-resolved measurements of light scattered at small angles by
      red blood cells in suspension.
AB  - Red blood cells (RBCs) scatter light mainly in the forward direction, where the
      scattering phase function has a narrow peak. We performed an experimental
      investigation into the angular distribution of light scattered by blood in the
      small-angle domain. A highly diluted suspension of RBCs (hematocrits in the range
      5 x 10(-5)-10(-2)) was illuminated with a He-Ne laser with 633 nm wavelength. We
      focused our research on two main topics: the scattering efficiency of the RBCs
      given by the mean scattering cross section and the scattering anisotropy obtained
      from the angular distribution of the scattered photons. The collimated beam
      transmission and the angular distribution of scattered light were measured and
      compared with the predictions of the effective phase function model. The RBCs'
      mean scattering cross section and scattering anisotropy were obtained by fitting
      of the experimental data.

PMID- 16579567
TI  - Fabrication and characterization of epitaxial Ba0.7Sr0.3TiO3 thin films for
      optical waveguide applications.
AB  - The optical properties of barium strontium titanate (Ba0.7Sr0.3TiO3; BST) thin
      films are described. The BST thin films were epitaxially grown upon MgO (001)
      substrates by pulsed laser deposition. The crystallographic properties of the BST
      thin films were examined by x-ray diffraction. The BST thin films were highly
      optically transparent in the visible region. The optical waveguide properties
      were characterized by a prism coupling technique. An inverse-WBK method was
      employed to determine the refractive-index profile along the thickness of the BST
      films. Optical losses were measured by a moving fiber method, and the optical
      losses were found to be 0.93 dB/cm for the TE0 mode and 1.29 dB/cm for the TM0
      mode at 1550 nm. Electro-optic (E-O) properties were measured by a phase
      modulation detection method at 632.8 nm, and the BST films exhibited a
      predominantly quadratic E-O effect with a quadratic E-O coefficient of 6.64 x 10(
      18) m2/V2.

PMID- 16579569
TI  - Polarization and higher-order content measurement of a soft-x-ray monochromatized
      beam with Mo-Si multilayers.
AB  - A Mo-Si multilayer mirror has been used for determination of the ellipticity and
      higher-order content of a synchrotron beam. The method is based on the angular
      measure of multilayer reflectivity in the region of Bragg first- and second-order
      reflections. Beam parameters were derived by a fitting procedure.

PMID- 16579568
TI  - Effects of temperature on columnar microstructure and recrystallization of TiO2
      film produced by ion-assisted deposition.
AB  - Titanium oxide thin films were deposited by electron-beam evaporation with ion
      beam-assisted deposition. The effect of the substrate temperature and annealing
      temperature on the columnar microstructure and recrystallization of titanium
      oxide was studied. The values of the refractive index varied from 2.26 to 2.4,
      indicating that the different substrate temperatures affected the film density. X
      ray diffraction revealed that all films were amorphous as deposited. At annealing
      temperatures from 100 degrees C to 300 degrees C, only the anatase phase was
      formed. As the substrate temperature increased from 150 degrees C to 200 degrees
      C to 250 degrees C, the recrystallization temperature fell from 300 degrees C
      through 250 degrees C to 200 degrees C. Changing the substrate temperature
      resulted in the formation of various types of columnar microstructure, as
      determined by scanning-electron microscopy. Different columnar structures
      resulted in different surface morphologies, as measured by atomic-force
      microscopy.

PMID- 16579570
TI  - Dynamic optical coupled system employing even-numbered dammann gratings.
AB  - Dammann gratings are well known for their ability to generate arrays of uniform
      intensity beams from an incoming monochromatic beam. We apply the even-numbered
      Dammann grating to achieve dynamic optical coupled technology. A 1 x N dynamic
      optical coupled system is developed by employing two complementary even-numbered
      Dammann gratings. With this system we can achieve a beam splitter and combiner as
      a switch between them according to the relative shift between the gratings. Also,
      this system is a preferable approach in integral packaging. More importantly,
      this device has the potential to be applied to the splitting of a large array,
      e.g., 8 x 16 array and 64 x 64 array, which is difficult to be realized with
      conventional splitting methods. We experimentally demonstrated a 1 x 8 coupler at
      the wavelength of 1550 nm. Furthermore we analyze the effects of the alignment
      errors between gratings and the wavelength-dependent error on efficiency and
      uniformity. The experimental results and the influence of alignment error and
      wavelength-dependent error are analyzed in detail.

PMID- 16579571
TI  - Radial mask for imaging systems that exhibit high resolution and extended depths
      of field.
AB  - A novel algorithm for the design of an imaging system that exhibits high
      resolution as well as extended depth of field is presented. This novel approach
      searches for an optimal pupil mask that minimizes the value of the mean-square
      error when performed over the intensity rather than in the field distribution of
      the acquired image. The captured images in such system do not require any
      postprocessing, and thus utilization of such a system is simplified. Simulations
      as well as experimental results are provided.

PMID- 16579572
TI  - Simulations of the accuracy in retrieving stratospheric aerosol effective radius,
      composition, and loading from infrared spectral transmission measurements.
AB  - We examine the extent to which three physical aerosol parameters--effective
      radius, composition (sulfate weight percent), and total volume-can be determined
      from infrared transmission spectra. Using simulated transmission data over the
      range 800-4750 cm(-1) (12.5-2.1 microm) and errors taken from the infrared
      spectral measurements of the Atmospheric Trace Molecule Spectroscopy (ATMOS)
      instrument, we use optimal estimation to recover these aerosol parameters.
      Uncertainties in these are examined as a function of the size, composition, and
      loading of stratospheric aerosols and of the spectral range employed. Using the
      entire spectral range above, we retrieve all three parameters with a precision to
      within 3% if the size distribution form is known. Additional errors result,
      however, from an uncertainty in the size distribution width. These are small
      (only a few percent) for composition and total volume but are substantial (as
      much as 50%) for effective radius. Errors also increase substantially when the
      spectral range is reduced. The retrieved effective radius can have an error of
      100% or greater for typical stratospheric aerosol sizes when the spectral range
      is restricted to the lower wavenumber part of the range. For good accuracy in
      effective radius, the spectral range must extend beyond approximately 3000 cm(
      1). Composition and total volume are less sensitive to the spectral range than
      effective radius. These simulations were carried out with modeled data to test
      the potential accuracy of stratospheric sulfate aerosol retrievals from the
      Atmospheric Chemistry Experiment (ACE). Because of the limitations that result
      from the use of simulated data, we have tested our retrieval algorithm using
      ATMOS spectra in different filter regions and present here the aerosol parameters
      obtained.

PMID- 16579573
TI  - Atmospheric transmittance of an absorbing gas. 7. Further improvements to the
      OPTRAN 6 approach.
AB  - We present recent improvements in accuracy to the fast transmittance-calculation
      procedure, Optical Path Transmittance (OPTRAN), which is used for satellite data
      assimilation at the National Oceanic and Atmospheric Administration. These
      improvements are (1) to change the absorber space used for ozone, (2) to add new
      predictors for each gas, and (3) to treat the water vapor line absorption and
      water continuum absorption as separate terms. Significant improvements in the
      accuracy of the OPTRAN algorithm for High-Resolution Infrared Radiation Sounders
      (HIRS) and the Atmospheric Infrared Sounder (AIRS) are demonstrated. The results
      that we show here extend a recent paper of Xiong and McMillin (2004) that
      describes the use of a polychromatic correction term to replace the effective
      transmittance concept to include additional changes that improve accuracy.

PMID- 16579574
TI  - Modal cutoff properties in germanium-doped photonic crystal fiber.
AB  - The germanium-doped photonic crystal fiber (PCF) has some characteristics that
      differentiate it from pure-silica PCF for a germanium element being doped in the
      core, such as the intensified nonlinearity, the enhanced photosensitivity, and so
      on. To pave the way for the application of the Ge-doped PCF successfully, it is
      necessary to study its properties. We investigated the modal cutoff properties of
      Ge-doped PCF quantitatively by using the beam propagation method. The numerical
      results show that the effective refractive indices and the normalized frequency V
      of Ge-doped PCF not only depend on the normalized pitch delta/lambda but also
      depend on the normalized hole size d/delta, the modal cutoff boundary for the
      single mode-multimode of the Ge-doped PCF shift to the low d/delta side in
      contrast to the pure-silica PCF.

PMID- 16579575
TI  - Dispersion analysis of hollow-core modes in ultralarge-bandwidth all-silica Bragg
      fibers with nanosupports.
AB  - Dispersion of the fundamental confined modes in hollow-core all-silica Bragg
      fibers with nanosupports is analyzed. The transfer-matrix formalism is applied.
      Anomalies in the group-velocity dispersion are evidenced at long wavelengths,
      toward the upper limit of the bandgap. The results confirm that, as in
      microstructured photonic crystal fibers, this anomalous dispersion is due to
      prevention of the confined hollow-core modes from crossing the surface modes, the
      avoided crossings are more apparent in the variation of group velocity with
      wavelength. The dependence of these avoided crossings on the hollow-core radius
      and the layer thicknesses is briefly analyzed.

PMID- 16579576
TI  - Forward-illumination light-extinction technique for soot measurement.
AB  - A forward-illumination light-extinction (FILE) soot volume fraction measurement
      technique was developed and tested. By using a camera and a point light source in
      front of the flame and a diffuser behind the flame, with this technique one can
      achieve a two-dimensional soot concentration measurement with only one window
      when one is studying confined combustion. The line-of-sight quantitative soot
      volume fraction is obtained by calculation of the reflected light intensity with
      or without the presence of soot cloud. Verification of this technique was
      accomplished by measurement of an axisymmetric ethylene diffusion flame. The
      field distribution obtained by Abel inversion is presented and matched well with
      previous point measurements. The FILE technique has high time resolution when a
      high-speed camera and a copper vapor laser are adopted. All these advantages of
      FILE make it suitable for line-of-sight integrated, two-dimensional soot
      distribution of transient combustion, e.g., in the case of in-cylinder Diesel
      combustion.

PMID- 16579577
TI  - Modeling and optimization of Q-switched double-clad fiber lasers.
AB  - The numerical modeling of actively Q-switched fiber lasers is systematically
      presented. On the basis of typical Q-switched ytterbium-doped double-clad fiber
      lasers under forward and backward pump, the dynamic characteristics of pulse
      energy, pulse width, population inversion, and stored energy at tens-of-kilohertz
      repetition rates are studied by using the traveling-wave method. The laser
      performance is further investigated for different fiber core diameters, doping
      rates, cavity lengths, fiber losses, signal and pump wavelengths, reflectivities
      of output coupler, and switching speed of an acousto-optic modulator; the laser
      optimization is also quantitatively discussed. Some simulation results are also
      compared with previous experimental results.

PMID- 16579578
TI  - Optical dephasing in saturable-absorbing organic dye IR140.
AB  - Room-temperature degenerate four-wave mixing in the forward two-pulse geometry,
      has been performed on ajet of organic saturable-absorbing laser dye IR140
      dissolved in dimethylsulfoxide and ethylene glycol. Numerical solutions to the
      optical Bloch equation were fitted to the experimental data in order to extract a
      value of T2 = 50 +/- 5 fs for the homogeneous dephasing time; this value is
      comparable to those measured for similar organic dyes using other techniques.

PMID- 16579579
TI  - Applicability of light-emitting diodes as light sources for active differential
      optical absorption spectroscopy measurements.
AB  - We present what is to our knowledge the first use of light-emitting diodes (LEDs)
      as light sources for long-path differential optical absorption spectroscopy (LP
      DOAS) measurements of trace gases in the open atmosphere. Modern LEDs represent a
      potentially advantageous alternative to thermal light sources, in particular to
      xenon arc lamps, which are the most common active DOAS light sources. The
      radiative properties of a variety of LEDs were characterized, and parameters such
      as spectral shape, spectral range, spectral stability, and ways in which they can
      be influenced by environmental factors were analyzed. The spectra of several LEDs
      were found to contain Fabry-Perot etalon-induced spectral structures that
      interfered with the DOAS evaluation, in particular when a constant temperature
      was not maintained. It was shown that LEDs can be used successfully as light
      sources in active DOAS experiments that measure NO2 and NO3 near 450 and 630 nm,
      respectively. Average detection limits of 0.3 parts in 10(9) and 16 parts in
      10(12) respectively, were obtained by use of a 6 km light path in the open
      atmosphere.

PMID- 16579580
TI  - Two-photon nitric oxide laser-induced fluorescence measurements in a diesel
      engine.
AB  - A two-photon nitric oxide (NO) laser-induced fluorescence (LIF) technique was
      developed and applied to study in-cylinder diesel combustion. The technique
      prevents many problems associated with in-cylinder, single-photon NO planar-laser
      induced fluorescence measurements, including fluorescence interference from the
      Schumann-Runge bands of hot O2, absorption of a UV excitation beam by in-cylinder
      gases, and difficulty in rejecting scattered laser light while simultaneously
      attempting to maximize fluorescence signal collection. Verification that the
      signal resulted from NO was provided by tuning of the laser to a vibrational off
      resonance wavelength that showed near-zero signal levels, which resulted from
      either fluorescence or interference at in-cylinder pressures of as much as 20
      bar. The two-photon NO LIF signal showed good qualitative agreement with NO
      exhaust-gas measurements obtained over a wide range of engine loads.

PMID- 16579581
TI  - Information content of point radiance measurements in turbid media: implications
      for interstitial optical property quantification.
AB  - Motivated by a recent report by Dickey et al. [Phys. Med. Biol. 46, 2359 (2001)],
      who demonstrated optical property retrieval by using relative radiance
      measurements at a single position, we investigate the uniqueness of relative
      radiance measurements for quantifying the optical properties of turbid media by
      studying the solutions of the diffusion and P3 approximations of the Boltzmann
      transfer equation for a point source. Using the P3 approximation, we investigate
      the potential of radiance measurements for optical property recovery by examining
      the optical property response surface for point radiance information. We further
      derive first-order similarity relations for relative point radiance measurements
      and use these expressions to examine analytically the effects of noise on optical
      property retrieval over a wide range of optical properties typical of biological
      tissue. Finally, optimal experimental configurations are studied and explicit
      conditions for uniqueness derived that suggest potential strategies for improving
      optical property recovery. It is expected that point radiance measurements will
      prove valuable for both on-line treatment planning of minimally invasive laser
      therapies and optical characterization of tissues.

PMID- 16579582
TI  - Technique for measurement of fluorescence lifetime by use of stroboscopic
      excitation and continuous-wave detection.
AB  - A study of the practicality a simple technique for obtaining time-domain
      information that uses continuous wave detection of fluorescence is presented. We
      show that this technique has potential for use in assays for which a change in
      the lifetime of an indicator occurs in reaction to an analyte, in fluorescence
      resonance energy transfer, for example, and could be particularly important when
      one is carrying out such measurements in the scaled-down environment of a lab on
      a chip (biochip). A rate-equation model is presented that allows an objective
      analysis to be made of the relative importance of the key measurement parameters:
      optical saturation of the fluorophore and period of the excitation pulse. An
      experimental demonstration of the technique that uses a cuvette-based analysis of
      a carbocyanine dye and for which the excitation source is a 650 nm wavelength,
      self-pulsing AlGaInP laser diode is compared with the model.

PMID- 16579584
TI  - The challenge of leadership.

PMID- 16579583
TI  - System performance evaluation of refractive surgical lasers: a mathematical
      approach.
AB  - A study was conducted for the purpose of improving the designs of the next
      generation of refractive surgical laser systems. Two common refractive laser
      systems, variable-spot scanning (type A) and small-spot scanning (type B), are
      discussed by identifying sources of error that could adversely affect the
      capability of these lasers to accurately produce complex, customized wavefront
      guided ablations. A mathematical model was used to construct a laser simulator
      that models the two common laser systems in terms of the root-mean-square error.
      Error sources from ablation profile fitting, ablation registration, eye tracking,
      and the laser delivery system are compared, and the relative contribution of each
      to the overall system error is analyzed. This system-level analysis can be
      helpful to the improvement of both laser systems.

PMID- 16579585
TI  - Nursing leadership in Texas.

PMID- 16579586
TI  - Texas Nurses Association testimony. National Occupational Research Agenda (NORA)
      town hall meeting, Houston, TX, January 23, 2006.

PMID- 16579587
TI  - The importance of mentoring. A tribute to Nell B Trew Burrous, RN, and faculty
      everywhere.

PMID- 16579588
TI  - Performance evaluation of a hybrid linear ion trap/orbitrap mass spectrometer.
AB  - Design and performance of a novel hybrid mass spectrometer is described. It
      couples a linear ion trap mass spectrometer to an orbitrap mass analyzer via an
      rf-only trapping quadrupole with a curved axis. The latter injects pulsed ion
      beams into a rapidly changing electric field in the orbitrap wherein they are
      trapped at high kinetic energies around an inner electrode. Image current
      detection is subsequently performed after a stable electrostatic field is
      achieved. Fourier transformation of the acquired transient allows wide mass range
      detection with high resolving power, mass accuracy, and dynamic range. The entire
      instrument operates in LC/MS mode (1 spectrum/s) with nominal mass resolving
      power of 60,000 and uses automatic gain control to provide high-accuracy mass
      measurements, within 2 ppm using internal standards and within 5 ppm with
      external calibration. The maximum resolving power exceeds 100,000 (fwhm). Rapid,
      automated data-dependent capabilities enable real-time acquisition of up to three
      high-mass accuracy MS/MS spectra per second.

PMID- 16579589
TI  - Measuring diffusion of molecules into individual polymer particles by confocal
      Raman microscopy.
AB  - Raman microscopy is a powerful method for providing spatially resolved,
      chemically selective information about the composition of materials. With
      confocal collection optics, the method is well suited to the analysis of small
      particles in contact with liquid solutions. In this work, the transport of an
      organic solvent component into small polystyrene particles is investigated. An
      inverted confocal Raman microscope is used to acquire spectra from individual 75
      microm polystyrene particles in contact with acetonitrile/water mixtures.
      Monitoring the Raman scattering from the C[triple bond]N stretching mode of
      acetonitrile provides a measure of solvent uptake into the polymer material. The
      small collection volume defined by the confocal optics provides the micrometer
      spatial resolution needed to track solvent concentration at different locations
      within the particle with 30-s time resolution. The volume fraction of
      acetonitrile in water in the surrounding solution was varied in order to
      determine the concentration dependence of the diffusion kinetics. Modeling the
      transport of molecules into a particle was addressed by using finite element
      methods for the evaluation of the coupled space- and time-dependent differential
      equations that govern the molecular transport. The results indicate that the
      diffusion coefficient changes with the local solvent concentration in the
      polymer. At longer times, with the highest acetonitrile concentrations, an
      evolution of the solvent transport mechanism was observed, from a diffusive rate
      that depends on local concentration to a linear increase in concentration with
      time accompanied by measurable swelling of the particle volume.

PMID- 16579590
TI  - Real-time measurement of oligomeric species in secondary organic aerosol with the
      aerosol time-of-flight mass spectrometer.
AB  - Real-time detection of oligomers in secondary organic aerosols has been carried
      out with an aerosol time-of-flight mass spectrometer sampling particles generated
      in a smog chamber. The photooxidation products of 1,3,5-trimethylbenzene and NOx
      were studied over a range of initial 1,3,5-trimethylbenzene concentrations (137
      1180 ppb), while keeping the 1,3,5-trimethylbenzene to NOx ratio nearly constant.
      The photooxidation products of a mixture of alpha-pinene (initial concentration
      191 ppb), 1,3,5-trimethylbenzene (60 ppb), and NOx were also investigated. In
      both systems, ions were observed in the single-particle mass spectra up to 750
      Da; the species observed differed in the two systems. These high-mass ions occur
      with characteristic spacing of 14 and 16 Da, indicative of oligomeric species.
      The results obtained agree well with off-line (matrix-assisted) laser
      desorption/ionization mass spectrometry results. The real-time capabilities of
      the aerosol time-of-flight mass spectrometer make it possible to investigate the
      temporal development of the oligomers with 5-min time resolution and also
      demonstrate that there are certain ions within the oligomer population that occur
      in nearly all of the particles and with relatively high signal intensity,
      suggesting that these ions have higher stability or that the species are formed
      preferentially.

PMID- 16579591
TI  - Charge transfer through DNA: A selective electrochemical DNA biosensor.
AB  - The charge-transfer properties of DNA duplexes are exploited to produce a fast,
      simple, sensitive, and selective DNA biosensor by exposing the DNA recognition
      interface to a sample containing target DNA and the redox-active intercalator,
      anthraquinonemonosulfonic acid (AQMS). Electrochemistry from electron transfer
      through the DNA to AQMS intercalated into DNA duplexes can be differentiated from
      electrochemistry due to direct access of the AQMS to the electrode surface due to
      the difference in the environment of the AQMS giving a shift in the potential at
      which the molecule is reduced. The ability to distinguish between the two
      electrochemical signals enables DNA hybridization to be monitored in real time.
      This in situ detection scheme has good selectivity, being able to differentiate
      between a complementary target DNA sequence and one containing either C-A or G-A
      single-base mismatches. The concentration detection limit of the biosensor is 0.5
      nM (1 pmol) with an assay time of 1 h. The fact that the end user is only
      required to simultaneously add the sample containing the target DNA and AQMS
      gives a DNA biosensor that is highly compatible with PCR on chip technologies.

PMID- 16579593
TI  - Practical constraints in the kinetic plot representation of chromatographic
      performance data: theory and application to experimental data.
AB  - It is demonstrated that the kinetic plot representation of experimental plate
      height data can also account for practical constraints on the column length, the
      peak width, the viscous heating, and the mobile-phase velocity without needing
      any iterative solution routine. This implies that the best possible kinetic
      performance to be expected from a given tested support under any possible set of
      practical optimization constraints can always be found using a directly
      responding calculation spreadsheet template. To show how the resulting
      constrained kinetic plots can be used as a powerful design and selection tool,
      the method has been applied to a series of plate height measurements performed on
      a number of different commercial columns for the same component (butyl-parabene)
      and mobile-phase composition. The method, for example, allows one to account for
      the fact that the advantageous solutions displayed by the silica monolith and 5
      microm particle columns in the large plate number range of the free kinetic plot
      are no longer accessible if applying a maximal column length constraint of Lmax =
      30 cm. In the plate number range that remains accessible, the investigated sub-2
      mum particle columns in any case perform (at least for the presently considered
      parabene separation) better than the 3.5 mum particle columns or silica monolith,
      especially if considering the use of system pressures exceeding 400 bar. The
      constrained kinetic plot method can also be used to select the best-suited column
      length from an available product gamma to perform a separation with a preset
      number of plates. One of the optimization results that is obtained in this case
      is that sometimes a significant gain in analysis time can be obtained by
      selecting a longer column, yielding the desired plate number at a larger velocity
      than that for a shorter column.

PMID- 16579592
TI  - Pro-CrossLink. Software tool for protein cross-linking and mass spectrometry.
AB  - To facilitate structural analysis of proteins and protein-protein interactions,
      we developed Pro-CrossLink, a suite of software tools consisting of three
      programs (Figure 1), DetectShift, IdentifyXLink, and AssignXLink. DetectShift was
      developed to detect ions of cross-linked peptide pairs in a mixture of 18O
      labeled peptides obtained from protein proteolytic digests. The selected
      candidate ions of cross-linked peptide pairs subsequently undergo tandem mass
      spectrometric (MS/MS) analysis for sequence determination. Based on the masses of
      candidate ions as well as y- and b-type ions in the tandem mass spectra,
      IdentifyXLink assigns the candidate ions to cross-linked peptide pairs. For an
      identified cross-linked peptide pair, AssignXLink generates an extensive fragment
      ion list, including a-, b-, c-type, x-, y-, z-type, internal, and immonium ions
      with associated common losses of H2O, NH3, CO, and CO2, and facilitates a precise
      location of the cross-linked residues. Pro-CrossLink is automated, highly
      configurable by the user, and applicable to many studies that map low-resolution
      protein structures and molecular interfaces in protein complexes.

PMID- 16579594
TI  - On-line monitoring and identification of bioaerosols.
AB  - Fast analysis of bioaerosols in clean room environments is necessary in order to
      prevent contamination of pharmaceutical products, minimize machine downtimes, or
      both. The detection and identification of microbes will be carried out in several
      steps: After impaction of the aerosol on a surface, the particles are presorted
      with glancing light illumination and fluorescence imaging in order to distinguish
      between abiotic and biotic particles. Since only the biotic particles are of
      interest, the analysis time can be minimized due to reduction of the data set.
      The biotic particles are then analyzed further with Raman spectroscopy and
      identified with a support vector machine.

PMID- 16579595
TI  - Accurate mass-driven analysis for the characterization of protein
      phosphorylation. Study of the human Chk2 protein kinase.
AB  - We describe the data-dependent analysis of protein phosphorylation using rapid
      acquisition nano-LC-linear quadrupole ion trap Fourier transform ion cyclotron
      resonance mass spectrometry (nano-LC-FTMS). The accurate m/z values of singly,
      doubly, and triply charged species calculated from the theoretical protonated
      masses of peptides phosphorylated at all Ser, Thr, or Tyr residues of the human
      checkpoint 2 (Chk2) protein kinase were used for selected ion extraction and
      chromatographic analysis. Using a kinase-inactive Chk2 mutant as a control,
      accurate mass measurements from FTMS and collision-induced dissociation spectra,
      11 novel Chk2 autophosphorylation sites were assigned. Additionally, the presence
      of additional Chk2 phosphorylation sites in two unique peptides was deduced from
      accurate mass measurements. Selected ion chromatograms of all Chk2
      phosphopeptides gave single peaks except in three cases in which two closely
      eluting species were observed. These pairs of phosphopeptides were determined to
      be positional isomers from MS/MS analysis. In this study, it was also found that
      ions due to the neutral loss of phosphoric acid from the parent peptide ion were
      not prominent in 18 of 36 MS/MS spectra of O-linked Chk2 phosphopeptides. Thus,
      accurate mass-driven analysis and rapid parallel MS/MS acquisition is a useful
      method for the discovery of new phosphorylation sites that is independent of the
      signature losses from phosphorylated amino acid residues.

PMID- 16579596
TI  - Electrochemical genosensor based on peptide nucleic acid-mediated PCR and
      asymmetric PCR techniques: Electrostatic interactions with a metal cation.
AB  - The unique structure of peptide nucleic acids (PNAs), linking the N-(2
      aminoethyl)glycine units that create a neutral backbone, and prevent it from
      acting as a primer for DNA polymerase, has been utilized in an electrochemical
      biosensor scheme for simple and sensitive detection of hybridization. When the
      PNA is targeted against a single-nucleotide polymorphism (SNP) or wild-type site
      on the gene, PNA-mediated polymerase chain reaction (PCR) clamping method
      effectively blocks the formation of a PCR product. In our report, PNA probe for
      PCR clamping was targeted against the wild-type site of alcohol dehydrogenase.
      The electrostatic interactions between the negatively charged DNA and neutral PNA
      molecules with redox-active metal cation cobalt(III)hexamine ([Co(NH3)6]3+) were
      monitored using differential pulse voltammetry. The electrostatic binding of
      [Co(NH3)6]3+ to DNA provided the basis for the discrimination against PNA/PNA,
      PNA/DNA, and DNA/DNA hybrid molecules. We have optimized the experimental
      conditions, such as probe concentration, [Co(NH3)6]3+ concentration, accumulation
      time for [Co(NH3)6]3+, and target concentration. A new pretreatment method has
      also been employed to allow fast and simple detection of hybridization reaction
      between the PCR amplicon and the probe on glassy carbon electrode (GCE) surface.
      This method was based on the application of a high-temperature treatment (95
      degrees C, 5 min), followed by a 1-min incubation in the presence of DNA primers.
      The excess concentration of DNA primers prevented the rehybridization of the
      denatured strands, while enabling the target gene sequence to bind with the
      immobilized probe. Additionally, asymmetric PCR was employed to detect the
      presence of genetically modified organism in standard Roundup Ready soybean
      samples. The amplicons of asymmetric PCR, which were predominantly single
      stranded DNA as a result of unequal primer concentration, hybridized with the DNA
      probe on the sensor surface efficiently. The attachment of long single-strands on
      GCE surface caused the accumulation of [Co(NH3)6]3+ and a high current response.
      Here, we report a versatile method that would allow for simple and rapid analysis
      of nucleic acids in combination with PNA-mediated PCR and asymmetric PCR
      techniques by using an electrochemical genosensor.

PMID- 16579597
TI  - Enhanced mixture analysis of poly(ethylene glycol) using high-field asymmetric
      waveform ion mobility spectrometry combined with fourier transform ion cyclotron
      resonance mass spectrometry.
AB  - The combination of high-field asymmetric waveform ion mobility spectrometry
      (FAIMS) with Fourier transform ion cyclotron resonance mass spectrometry (FTICR
      MS) makes possible lower detection limits, increased sensitivity, and increased
      dynamic range in the analysis of poly(ethylene glycol) (PEG) samples of low
      molecular weight. The signal gain obtained using FAIMS depends on ion identity,
      with a range between 1.8x and 14x obtained for various molecular ions of PEG 600.
      A 1.7-fold reduction in noise is obtained using FAIMS due to the elimination of
      chemical noise. The improved detection performance is predominantly due to a
      reduction in adverse Coulomb effects as a result of ions being selectively
      introduced into the mass spectrometer. The high ion transmission obtained using
      FAIMS combined with the high sensitivity of FTICR-MS detection make possible
      separation of multiple gas-phase conformers of PEG molecular cations that have
      low abundance (less than 0.2% relative abundance) and that have not been detected
      previously. Mixed dications of PEG that have the same nominal mass but differ by
      the number polymer subunits (m/Delta m up to 25,000) can be separately introduced
      into the mass spectrometer using FAIMS. Interactions of the carrier gas with the
      metal ions that are attached to the PEG molecules appear to be the most
      significant factor in these FAIMS separations.

PMID- 16579599
TI  - Ultralow-volume fraction collection from NanoLC columns for mass spectrometric
      analysis of protein phosphorylation and glycosylation.
AB  - An ultralow volume fraction collection system referred to as nano fraction
      analysis chip technology (nanoFACT) is reported. The system collects 25-2500-nL
      fractions from 75-microm nanoLC columns into pipet tips at a user-defined, timed
      interval, typically one fraction every 15-120 s. Following collection, the
      fractions in the tip dry down naturally on their own in such a way as to create a
      concentrated band at the very end of the interior of the pipet tip. The fractions
      are then reconstituted directly in the pipet tips in approximately 250 nL of
      solvent prior to analysis. Because the chromatography and reconstitution solvent
      are independent, the reconstitution solvent can be selected to maximize
      ionization efficiency without compromising chromatography. In the infusion
      analysis of the nanoLC fractions, a low-flow electrospray chip is used which
      consists of 400 nozzles, each with an inner diameter of 2.5 microm and yielding
      flow rates of approximately 20 nL/min. Therefore, when reconstituted in 250 nL,
      each nanoLC fraction can be analyzed for over 10 min. This increase in analysis
      time allows for signal averaging, resulting in higher data quality, collision
      energy optimization, slower scanning techniques to be used, such as neutral loss
      and precursor ion scanning, higher resolution scans on FTMS instruments, and
      improved peptide quantitation. Furthermore, the nanoLC fractions could be
      archived in the pipet tips for analysis at a later date. Here, the advantages of
      nanoFACT are shown for phosphorylation analysis using bovine fetuin and
      glycosylation analysis using bovine ribonuclease B (RNase B). In the
      phosphorylation analysis, a comparison between conventional nanoLC and a nanoFACT
      analysis was performed. An MS/MS spectrum of a triply phosphorylated peptide, 313
      HTFSGVApSVEpSpSSGEAFHVGK-333 could only be obtained using nanoFACT, not with
      nanoLC. Furthermore, spectral quality for the nanoFACT analysis was significantly
      improved over nanoLC. This was determined by comparing the number of diagnostic
      ions between the nanoFACT and nanoLC spectra, and it was found that the nanoFACT
      spectra contained a 19% or greater number of diagnostic ions for
      nonphosphorylated peptides and 55% or greater for phosphorylated peptides. For
      the glycosylation analysis, the glycosylation site of RNase B was fully
      characterized using 100 fmol of tryptic digest on a three-dimensional ion trap
      mass spectrometer.

PMID- 16579598
TI  - Assessment of analytical reproducibility of 1H NMR spectroscopy based
      metabonomics for large-scale epidemiological research: the INTERMAP Study.
AB  - Large-scale population phenotyping for molecular epidemiological studies is
      subject to all the usual criteria of analytical chemistry. As part of a major
      phenotyping investigation we have used high-resolution 1H NMR spectroscopy to
      characterize 24-h urine specimens obtained from population samples in Aito Town,
      Japan (n = 259), Chicago, IL (n = 315), and Guangxi, China (n = 278). We have
      investigated analytical reproducibility, urine specimen storage procedures,
      interinstrument variability, and split specimen detection. Our data show that the
      multivariate analytical reproducibility of the NMR screening platform was >98%
      and that most classification errors were due to urine specimen handling
      inhomogeneity. Differences in metabolite profiles were then assessed for Aito
      Town, Chicago, and Guangxi population samples; novel combinations of biomarkers
      were detected that separated the population samples. These cross-population
      differences in urinary metabolites could be related to genetic, dietary, and gut
      microbial factors.

PMID- 16579600
TI  - Rapid melting curve analysis on monolayered beads for high-throughput genotyping
      of single-nucleotide polymorphisms.
AB  - This report describes a rapid solid-phase melting curve analysis method for
      single-nucleotide polymorphism (SNP) genotyping. The melting curve analysis is
      based on dynamic allele-specific hybridization (DASH). The DNA duplexes are
      conjugated on beads that are immobilized on the surface of a microheater chip
      with integrated heaters and temperature sensors. SNP on PCR products were scored,
      illustrating the sensitivity and robustness of the system. The method is based on
      random bead immobilization by microcontact printing. Single-bead detection and
      multiplexing were performed with a heating rate more than 20 times faster than
      conventional DASH. Analyses that took more than 15 min could be performed in less
      that 1 min, enabling ultrarapid SNP analysis. In addition, an array version of
      the chip was implemented enabling the preparation of an array of bead arrays for
      high-throughput and rapid SNP genotyping.

PMID- 16579601
TI  - SPR imaging of photo-cross-linked small-molecule arrays on gold.
AB  - Identification of small-molecule ligands for a protein of interest can facilitate
      the analysis of the protein's functions in biological systems. Small-molecule
      microarrays have allowed for rapid detection of such ligand-protein interactions
      in a high-throughput manner, although a label on a protein is needed to observe
      these interactions. By combining SPR imaging technology with our recently
      developed photo-cross-linked small-molecule array platform, we developed a novel
      platform that allows in situ observation of interactions between photo-cross
      linked small molecules on gold surfaces and nonlabeled proteins in solution.
      Interactions of estrogenic and androgenic substances with estrogen receptor alpha
      were observed using this platform.

PMID- 16579602
TI  - pH response of carboxy-terminated colorimetric polydiacetylene vesicles.
AB  - Carboxy-terminated polydiacetylene vesicles are known to undergo dramatic color
      transitions in response to exposure to external stimuli such as pH, temperature,
      and receptor-ligand binding. FTIR spectroscopy was used to identify the breakdown
      in the interfacial hydrogen-bonding interactions of the carboxylic acid
      headgroups of polymerized 10,12-tricosadiynoic acid (TRCDA) vesicles in aqueous
      solution during pH chromic transition. The headgroup structure was monitored as
      the chromic transition takes place and the dissociation dependence of the pKa was
      determined. Due to the attenuated acidity of the interfacially confined carboxy
      groups, which exhibit pKa values in the range 9.5-9.9, it was found that the
      deprotonation-triggered blue-red chromic transition occurred in the pH range 9.0
      10.1 and that the mechanism of the transition required interaction with the
      surface carboxyl group, which is of importance in the design of a biochromic
      mechanism using PDA assemblies. Transmission electron microscopy and FTIR
      spectroscopy revealed that the surface ionization and the pH-induced chromogenic
      transition was also accompanied by a dramatic vesicle-planar morphological
      transition alongside subtle changes to the alkyl chain conformation and packing.
      A two-step mechanism was implicated as causing the chromic transition that first
      involves surface deprotonation and then specific cation binding, which can aid
      the design of sensitive surface-ligand chemistry for new PDA structures.

PMID- 16579603
TI  - Structural characterization of glycopeptides by N-terminal protein ladder
      sequencing.
AB  - High-sensitivity and high-throughput mass spectrometry (MS) has become an
      important tool for characterizing glycopeptides. Here, we analyzed synthetic O
      linked glycopeptides using matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF) MS. First, we applied MALDI-quadrupole ion trap (QIT)-TOF MS,
      which enables collision-induced dissociation-MSn analysis for fine structural
      characterization. Subsequent MS/MS of sodium adduct ions selected as precursor
      ions yielded detailed information about the site of oligosaccharide attachment as
      well as the carbohydrate and amino acid sequences; however, these MS/MS spectra
      were very complex. To obtain easily interpretable and simple spectra, we used N
      terminal protein ladder sequencing coupled with MALDI-TOF MS. From the extremely
      simple resulting spectra, we were able to determine the glycosylation sites,
      amino acid sequences, and oligosaccharide molecular weights of the glycopeptides.

PMID- 16579604
TI  - Immunoenzymometric assay for a small molecule,11-deoxycortisol, with attomole
      range sensitivity employing an scFv-enzyme fusion protein and anti-idiotype
      antibodies.
AB  - To overcome the sensitivity limit in immunoassays for small molecules (haptens),
      we established a noncompetitive immunoenzymometric assay (IEMA) format that can
      detect attomole-range hapten molecules. We selected 11-deoxycortisol (11-DC; Mr
      346.5), a corticosteroid serving a diagnostic index for pituitary-adrenal
      function, as a model target hapten. A fusion of a single-chain Fv fragment (scFv)
      specific for 11-DC and alkaline phosphatase (ALP) was generated for use as an
      enzyme-labeled antibody, instead of the conventional chemically linked enzyme
      antibody conjugates. After binding reaction of 11-DC and fixed amounts of the
      fusion protein (scFv-ALP), the unbound fusion protein was removed by incubation
      with a mouse beta-type anti-idiotype antibody recognizing the scFv paratope.
      These complexes were captured by magnetic separation using anti-mouse IgG
      antibody-coated magnetic beads. Following magnetic sedimentation of the beads,
      immune complexes of scFv-ALP and 11-DC remained in the supernatant were further
      purified by capture on microtiter plates with immobilized alpha-type anti
      idiotype antibody. As measured fluorometrically, ALP activity from bound immune
      complexes on the plates increased with increasing 11-DC, which is characteristic
      of a noncompetitive relationship. This IEMA afforded an extremely low detection
      limit (20 amol/assay), a very wide measurable range, and practical specificity.
      The plasma 11-DC levels determined for healthy subjects were validated as
      reliable.

PMID- 16579605
TI  - Evaluation of flow cell detector configurations combining simultaneous
      preconcentration and scintillation detection for monitoring of pertechnetate in
      aqueous media.
AB  - Flow cell detectors were developed for simultaneous concentration and
      scintillation detection of technetium-99 in water. Evaluated flow cell geometries
      consisted of a coil and a fountain flow cell design; the latter is based on
      radial solution flow through a resin bed interfaced with a photomultiplier tube
      through a polycarbonate window. The sorptive scintillating media investigated
      were (1) an extractive scintillator combining a porous polystyrene resin with the
      extractant Aliquat-336 and fluor 2-(1-naphthyl)-5-phenyloxazole, (2) a mixed bed
      of organic scintillator (BC-400) and Tc-selective resin (TEVA), and (3) a mixed
      bed of inorganic scintillator particles (CaF2-Eu) with either TEVA resin or
      strong base anion-exchange resin (Dowex 1 x 8-400(Cl)). Depending on flow cell
      geometry and medium, the detection efficiencies for 99Tc ranged from 7.26 (BC
      400/TEVA in coil geometry) to 50.20% (CaF2(Eu)/Dowex 1 x 8-400(Cl) in fountain
      flow cell geometry). The configuration with the highest sensitivity,
      CaF2(Eu)/Dowex 1 x 8-400(Cl) in coil geometry, can detect 99Tc as low as 3.78 Bq
      L(-1) for a 100-s count interval and a 200-mL sample, which is below the current
      regulatory level of 33 Bq L(-1). The issue of sensor reusability was addressed in
      this research, and its potential application at near neutral pH was demonstrated.
      The optimal sensor design was evaluated with a 99Tc-spiked synthetic groundwater
      matrix.

PMID- 16579606
TI  - Scaling and normalization effects in NMR spectroscopic metabonomic data sets.
AB  - Considerable confusion appears to exist in the metabonomics literature as to the
      real need for, and the role of, preprocessing the acquired spectroscopic data. A
      number of studies have presented various data manipulation approaches, some
      suggesting an optimum method. In metabonomics, data are usually presented as a
      table where each row relates to a given sample or analytical experiment and each
      column corresponds to a single measurement in that experiment, typically
      individual spectral peak intensities or metabolite concentrations. Here we
      suggest definitions for and discuss the operations usually termed normalization
      (a table row operation) and scaling (a table column operation) and demonstrate
      their need in 1H NMR spectroscopic data sets derived from urine. The problems
      associated with "binned" data (i.e., values integrated over discrete spectral
      regions) are also discussed, and the particular biological context problems of
      analytical data on urine are highlighted. It is shown that care must be exercised
      in calculation of correlation coefficients for data sets where normalization to a
      constant sum is used. Analogous considerations will be needed for other
      biofluids, other analytical approaches (e.g., HPLC-MS), and indeed for other
      "omics" techniques (i.e., transcriptomics or proteomics) and for integrated
      studies with "fused" data sets. It is concluded that data preprocessing is
      context dependent and there can be no single method for general use.

PMID- 16579607
TI  - Nucleic acid-functionalized Pt nanoparticles: Catalytic labels for the amplified
      electrochemical detection of biomolecules.
AB  - Nucleic acid-functionalized Pt nanoparticles (Pt-NPs) act as catalytic labels for
      the amplified electrochemical detection of DNA hybridization and aptamer/protein
      recognition. Hybridization of the nucleic acid-modified Pt-NPs with a sensing
      nucleic acid/analyte DNA complex associated with an electrode enables the
      amperometric, amplified, detection of the DNA by the Pt NP electrocatalyzed
      reduction of H2O2 (sensitivity limit, 1 x 10(-11) M). Similarly, the association
      of aptamer-functionalized Pt- NPs to a thrombin aptamer/thrombin complex
      associated with an electrode allowed the amplified, electrocatalytic detection of
      thrombin with a sensitivity limit corresponding to 1 x 10(-9) M.

PMID- 16579608
TI  - Quantitative 3D mapping of fluidic temperatures within microchannel networks
      using fluorescence lifetime imaging.
AB  - We describe a novel method for quantitatively mapping fluidic temperature with
      high spatial resolution within microchannels using fluorescence lifetime imaging
      in an optically sectioning microscope. Unlike intensity-based measurements, this
      approach is independent of experimental parameters, such as dye concentration and
      excitation/detection efficiency, thereby facilitating quantitative temperature
      mapping. Micrometer spatial resolution of 3D temperature distributions is readily
      achieved with an optical sectioning approach based on two-photon excitation. We
      demonstrate this technique for mapping of temperature variations across a
      microfluidic chip under different heating profiles and for mapping of the 3D
      temperature distribution across a single microchannel under applied flow
      conditions. This technique allows optimization of the chip design for
      miniaturized processes, such as on-chip PCR, for which precise temperature
      control is important.

PMID- 16579609
TI  - TNT detection using multiplexed liquid array displacement immunoassays.
AB  - The presence of trace contamination of soil and groundwater with explosives is an
      ongoing concern, for which improved methods are required to facilitate their
      detection and quantification. This is true both for the monitoring of remediation
      and for site characterization. Immunosensors have been found effective for
      solution-phase detection of environmental contaminants. Our work utilized the
      Luminex100 (flow cytometer) to detect TNT in a multiplexed displacement
      immunoassay format. The Luminex100 can perform a multiplexed assay by
      discriminating between up to 100 different bead sets. We used this capability to
      evaluate four different TNT monoclonal antibodies, two recombinant TNT
      antibodies, and a control antibody simultaneously for the rapid detection of TNT
      and other nitroaromatics. TNT could be detected at 0.1 ppb and quantified over
      the range of 1.0 ppb to 10 ppm. In addition, the assay was shown to be effective
      in various matrixes such as lake water, seawater, and acetone extracts of soil.
      Seawater required dilution with two parts buffer to avoid loss of microspheres,
      while the acetone extracts were diluted 100-fold or more to minimize solvent
      affects.

PMID- 16579611
TI  - Continuous ultrasound-assisted extraction coupled to flow injection
      pervaporation, derivatization, and spectrophotometric detection for the
      determination of ammonia in cigarettes.
AB  - A dynamic system for the continuous removal of ammonia from cigarettes with
      ultrasound assistance and iterative change of the flow direction of the
      extractant through the sample cell has been developed. A 0.1-g sample of
      cigarette was subjected to 7 min of ultrasound-assisted extraction (application
      and duration of pulse 0.7 s, output amplitude 85% of the converter nominal
      amplitude), and 1 M NaOH solution was used both as extractant and as carrier in
      the dynamic system. The ultrasound-assisted extractor was coupled to a
      pervaporation unit through a flow injection interface in order to develop a fully
      automated method. In arriving at the pervaporator, the ammonia is transferred
      from the donor-carrier stream to an acceptor stream, where the classical
      Berthelot reaction takes place--thus favoring pervaporation. The blue complex
      formed is spectrophotometrically monitored at 655 nm. The method was applied to
      the determination of ammonia in a selection of 10 European cigarette brands and
      Kentucky Reference 2R4F cigarettes.

PMID- 16579610
TI  - Integration of two-dimensional LC-MS with multivariate statistics for comparative
      analysis of proteomic samples.
AB  - LC-MS-based proteomics requires methods with high peak capacity and a high degree
      of automation, integrated with data-handling tools able to cope with the massive
      data produced and able to quantitatively compare them. This paper describes an
      off-line two-dimensional (2D) LC-MS method and its integration with software
      tools for data preprocessing and multivariate statistical analysis. The 2D LC-MS
      method was optimized in order to minimize peptide loss prior to sample injection
      and during the collection step after the first LC dimension, thus minimizing
      errors from off-column sample handling. The second dimension was run in fully
      automated mode, injecting onto a nanoscale LC-MS system a series of more than 100
      samples, representing fractions collected in the first dimension (8
      fractions/sample). As a model study, the method was applied to finding biomarkers
      for the antiinflammatory properties of zilpaterol, which are coupled to the beta2
      adrenergic receptor. Secreted proteomes from U937 macrophages exposed to
      lipopolysaccharide in the presence or absence of propanolol or zilpaterol were
      analysed. Multivariate statistical analysis of 2D LC-MS data, based on principal
      component analysis, and subsequent targeted LC-MS/MS identification of peptides
      of interest demonstrated the applicability of the approach.

PMID- 16579612
TI  - Separation of trace level hafnium from tungsten: a step toward solving an
      astronomical puzzle.
AB  - 182Hf (T(1/2) = 9 x 10(6) y) is believed to be formed by pure r-process during a
      supernova explosion, and therefore, the search for minute traces of 182Hf in the
      earth's crust is of great interest. Only accelerator mass spectrometry (AMS) is
      well suited for detecting such low levels of 182Hf. But any attempt to measure
      182Hf by AMS must ensure that the sample is free from its naturally occurring
      stable isobar 182W. A simple method for separation of tungsten and hafnium has
      been developed using radiometric simulation followed by checking the
      decontamination of tungsten from Hf in a synthetic sample by AMS. The separation
      studies were performed by a liquid-liquid extraction technique using tri-n
      octylamine (TOA) as the organic reagent. It has been found that a very high
      separation factor (1.6 x 10(6)) can be achieved when 0.3 M TOA diluted in
      cyclohexane is used as the organic phase and 6 M HCl (in the presence of small
      amount of H2O2) is used as the aqueous phase.

PMID- 16579613
TI  - Quantification of small therapeutic proteins in plasma by liquid chromatography
      tandem mass spectrometry: application to an elastase inhibitor EPI-hNE4.
AB  - LC/ESI-MS/MS is a promising alternative to immunoassays in improving the analysis
      of recombinant therapeutic proteins in biological fluids for toxicity and
      pharmacokinetics purposes. To assess the sensitivity and validation issues
      associated with this technique, we use here as a model EPI-hNE4, a 56-amino acid
      recombinant protein, and demonstrate that a method based on tandem mass
      spectrometry combined with liquid chromatography and electrospray interface can
      reach sensitivity similar to that of ELISA but without its potential cross
      reactivity. For this purpose, a triple quadrupole mass spectrometer operating in
      positive ion and single reaction monitoring mode with transition, m/z 1040 -->
      1224.5, was used for selective peak detection. Particular issues related to the
      internal standard, i.e., elution and ionization patterns similar to the protein
      without stable isotope labeling, and to analytical interference due to endogenous
      binding antibodies were addressed. A limit of quantification in human or monkey
      plasma of 5 ng/mL was reached with a sample volume of 100 microL, corresponding
      to 40 fmol injected into the HPLC column. Intra- and interassay precision and
      accuracy were below 15%. No matrix effect was detected.

PMID- 16579614
TI  - Hybridization probe for femtomolar quantification of selected nucleic acid
      sequences on a disposable electrode.
AB  - Mixed monolayers of electroactive hybridization probes on gold surfaces of a
      disposable electrode were investigated as a technology for simple, sensitive,
      selective, and rapid gene identification. Hybridization to the ferrocene-labeled
      hairpin probes reproducibly diminished cyclic redox currents, presumably due to a
      displacement of the label from the electrode. Observed peak current densities
      were roughly 1000x greater than those observed in previous studies, such that
      results could easily be interpreted without the use of algorithms to correct for
      background polarization currents. Probes were sensitive to hybridization with a
      number of oligonucleotide sequences with varying homology, but target
      oligonucleotides could be distinguished from competing nontarget sequences based
      on unique "melting" profiles from the probe. Detection limits were demonstrated
      down to nearly 100 fM, which may be low enough to identify certain genetic
      conditions or infections without amplification. This technology has rich
      potential for use in field devices for gene identification as well as in gene
      microarrays.

PMID- 16579615
TI  - On-chip millionfold sample stacking using transient isotachophoresis.
AB  - We present a simple and robust isotachophoresis (ITP) method that can be
      integrated with microchip-based capillary electrophoresis (CE) devices to achieve
      millionfold sample stacking. We performed an experimental parametric study to
      show the effects of initial sample ion concentration, leading ion concentration,
      and trailing ion concentration on ITP stacking. We also discuss the usefulness
      and limitations of a simple one-dimensional nondispersive model and a scaling
      analysis for dispersion rate. We found that a single-column ITP configuration
      together with electroosmotic flow suppression and high leading ion concentration
      provide high-performance ITP and can be integrated readily with CE separation. We
      demonstrated detection of trace of 100 fM Alexa Fluor 488 (signal-to-noise ratio
      of 11) with a concentration increase of a factor of 2 x 10(6). Application of our
      ITP/CE protocol to the stacking and separation of negatively charged fluorescent
      tracers (Alexa Fluor 488 and bodipy) resulted in a concentration increase of 6.4
      x 10(4) and a signal increase of 4.5 x 10(5). The ITP/CE protocol can be
      performed with a standard microchannel cross design or simple flow control. The
      method can be implemented with available off-the-shelf chip systems using off-the
      shelf voltage control systems and buffer chemistries.

PMID- 16579616
TI  - Use of piezoelectric-excited millimeter-sized cantilever sensors to measure
      albumin interaction with self-assembled monolayers of alkanethiols having
      different functional headgroups.
AB  - In this paper, we describe a new modality of measuring human serum albumin (HSA)
      adsorption continuously on CH3-, COOH-, and OH-terminated self-assembled
      monolayers (SAMs) of C11-alkanethiols and the direct quantification of the
      adsorbed amount. A gold-coated piezoelectric-excited millimeter-sized cantilever
      (PEMC) sensor of 6-mm2 sensing area was fabricated, where resonant frequency
      decreases upon mass increase. The resonant frequency in air of the detection peak
      was 45.5 +/- 0.01 kHz. SAMs of C11-thiols (in absolute ethanol) with different
      end groups was prepared on the PEMC sensor and then exposed to buffer solution
      containing HSA at 10 microg/mL. The resonant frequency decreased exponentially
      and reached a steady-state value within 30 min. The decrease in resonant
      frequency indicates that the mass of the sensor increased due to HSA adsorption
      onto the SAM layer. The frequency change obtained for the HSA adsorption on CH3-,
      COOH-, and OH-terminated SAM were 520.8 +/- 8.6 (n = 3), 290.4 +/- 6.1 (n = 2),
      and 210.6 +/- 8.1 Hz (n = 3), respectively. These results confirm prior
      conclusions that albumin adsorption decreased in the order, CH(3) > COOH > OH.
      Observed binding rate constants were 0.163 +/- 0.003, 0.248 +/- 0.006, and 0.381
      +/- 0.001 min(-1), for methyl, carboxylic, and hydroxyl end groups, respectively.
      The significance of the results reported here is that both the formation of self
      assembled monolayers and adsorption of serum protein onto the formed layer can be
      measured continuously, and quantification of the adsorbed amount can be
      determined directly.

PMID- 16579617
TI  - Nanofluidic injection and heterogeneous kinetics of organomercaptan surface
      displacement reactions on colloidal gold in a microfluidic stream.
AB  - Colloidal gold is developed as a molecular capture reagent in hybrid nanofluidic
      microfluidic devices for mass-limited sample analysis. Two fluorescent
      organomercaptans are injected through a nanocapillary array membrane and
      subsequently captured at the surface of 19-nm-diameter colloidal Au
      nanoparticles. The surface displacement kinetics are monitored via quenching of
      the organomercaptan fluorescence by the metallic particles coupled to a distance
      time conversion based on fluid velocity in the microfluidic channel using the
      point of mixing as the zero of time. The adsorbate concentration, colloid
      concentration, and fluid velocity are varied to determine the surface
      displacement rate constants for these heterogeneous reactions in the microfluidic
      device. Surface displacement rate constants are approximately 10(4) M(-1) s(-1)
      for a small organic molecule and for an octapeptide. These values are similar to
      values determined in macroscale measurements made with a traditional fluorometer
      and are 1 order of magnitude larger than values reported for adsorption of
      organomercaptans on planar Au, indicating faster kinetics in the colloid
      adsorbate system. These results highlight the utility of colloidal Au
      nanoparticles as molecular carriers for the sequestration of analytes, allowing
      the manipulation of mass-limited samples and ultimately the capture and delivery
      of selected analytes from a microfabricated device to an off-line detector.

PMID- 16579618
TI  - Multi-technique comparison of immobilized and hybridized oligonucleotide surface
      density on commercial amine-reactive microarray slides.
AB  - To establish a quantitative, corroborative understanding of observed correlations
      between immobilized probe DNA density on microarray surfaces and target
      hybridization efficiency in biological samples, we have characterized amine
      terminated, single-stranded DNA probes attached to amine-reactive commercial
      microarray slides and complementary DNA target hybridization using fluorescence
      imaging, X-ray photoelectron spectroscopy (XPS) and 32P-radiometric assays.
      Importantly, we have reproduced DNA probe microarray immobilization densities in
      macroscopic spotted dimensions using high ionic strength, high-concentration DNA
      probe solutions to permit direct XPS surface analysis of DNA surface chemistry
      with good reliability and reproducibility. Target capture hybridization
      efficiency with complementary DNA exhibited an optimum value at intermediate DNA
      probe immobilization densities. The macroscopic array model provides a new
      platform for the study of DNA surface chemistry using highly sensitive,
      quantitative surface analytical techniques (e.g., XPS, ToF-SIMS). Sensitive 32P
      DNA radiometric density measurements were calibrated with more routine XPS DNA
      signals, facilitating future routine DNA density determinations without the use
      of a hazardous radioactive assay. The objective is to provide new insight into
      different surface chemistry influences on immobilized DNA probe environments that
      affect target capture efficiency from solution to improve microarray assay
      performance.

PMID- 16579619
TI  - Control of the oxygen dependence of an implantable polymer/enzyme composite
      biosensor for glutamate.
AB  - Biosensors for glutamate (Glu) were fabricated from Teflon-coated Pt wire
      (cylinders and disks), modified with the enzyme glutamate oxidase (GluOx) and
      electrosynthesized polymer PPD, poly(o-phenylenediamine). The polymer/enzyme
      layer was deposited in two configurations: enzyme before polymer (GluOx/PPD) and
      enzyme after polymer (PPD/GluOx). These four biosensor designs were characterized
      in terms of response time, limit of detection, Michaelis-Menten parameters for
      Glu (J max and K(M)(Glu)), sensitivity to Glu in the linear response region, and
      dependence on oxygen concentration, K(M)(O2). Analysis showed that the two
      polymer/enzyme configurations behaved similarly on both cylinders and disks.
      Although the two geometries showed different behaviors, these differences could
      be explained in terms of higher enzyme loading density on the disks; in many
      analyses, the four designs behaved like a single population with a range of GluOx
      loading. Enzyme loading was the key to controlling the K(M)(O2) values of these
      first generation biosensors. The counterintuitive, and beneficial, behavior that
      biosensors with higher GluOx loading displayed a lower oxygen dependence was
      explained in terms of the effects of enzyme loading on the affinity of GluOx for
      its anionic substrate. Some differences between the properties of surface
      immobilized GluOx and glucose oxidase are highlighted.

PMID- 16579620
TI  - Electrogenerated chemiluminescence in polyelectrolyte multilayers: efficiency and
      mechanism.
AB  - The presence of an ultrathin film of polyelectrolyte complex, formed by the
      multilayering method, on an electrode was shown to enhance the intensity of
      electrogenerated chemiluminescence (ECL) from the
      tris(2,2')bipyridylruthenium(II)/tripropylamine system. Platinum electrodes
      coated with up to 17 layers of poly(diallyldimethylammonium chloride) or
      poly(vinylmethylpyridine), alternately layered with poly(styrenesulfonate),
      revealed significant differences in enhancement of ECL, depending on the identity
      of the multilayer. ECL following deposition of each layer showed an oscillating
      intensity of light emission, which alludes to the importance of surface and bulk
      charge. This effect, along with others, such as increased output with increasing
      tripropylamine concentration, was used to suggest a mechanism for enhanced ECL
      intensity at multilayer-coated electrodes.

PMID- 16579621
TI  - Application of ion attachment mass spectrometry to evolved gas analysis for in
      situ monitoring of porous ceramic processing.
AB  - Ion attachment mass spectrometry was applied to evolved gas analysis-mass
      spectrometry (EGA-MS), generally known as thermogravimetry-mass spectrometry.
      Characteristic species arising from poly(vinyl alcohol) (PVA) and poly(methyl
      methacrylate) (PMMA) resin, used as a binder and a porogen, respectively, in the
      starting materials for porous ceramics, were detected in the mass spectra. The
      EGA curves of the characteristic mass peaks from PVA and PMMA, when plotted
      against the programmed temperature, successfully showed the individual pyrolysis
      behavior of each polymer during the firing process.

PMID- 16579622
TI  - Formation of pyroglutamic acid from N-terminal glutamic acid in immunoglobulin
      gamma antibodies.
AB  - The status of the N-terminus of proteins is important for amino acid sequencing
      by Edman degradation, protein identification by shotgun and top-down techniques,
      and to uncover biological functions, which may be associated with modifications.
      In this study, we investigated the pyroglutamic acid formation from N-terminal
      glutamic acid residues in recombinant monoclonal antibodies. Almost half the
      antibodies reported in the literature contain a glutamic acid residue at the N
      terminus of the light or the heavy chain. Our reversed-phase high-performance
      liquid chromatography-mass spectrometry method could separate the pyroglutamic
      acid-containing light chains from the native light chains of reduced and
      alkylated recombinant monoclonal antibodies. Tryptic peptide mapping and tandem
      mass spectrometry of the reduced and alkylated proteins was used for the
      identification of the pyroglutamic acid. We identified the formation of
      pyroglutamic acid from N-terminal glutamic acid in the heavy chains and light
      chains of several antibodies, indicating that this nonenzymatic reaction does
      occur very commonly and can be detected after a few weeks of incubation at 37 and
      45 degrees C. The rate of this reaction was measured in several aqueous buffers
      with different pH values, showing minimal formation of pyroglutamic acid at pH
      6.2 and increased formation of pyroglutamic acid at pH 4 and pH 8. The half-life
      of the N-terminal glutamic acid was approximately 9 months in a pH 4.1 buffer at
      45 degrees C. To our knowledge, we showed for the first time that glutamic acid
      residues located at the N-terminus of proteins undergo pyroglutamic acid
      formation in vitro.

PMID- 16579623
TI  - Method for the analysis of delta18O in water.
AB  - A new method has been developed for the oxygen isotopic analysis of water
      utilizing the exchange of oxygen atoms with nitrite followed by conversion of
      nitrite to nitrous oxide by hydrazoic acid. This method is analogous to that
      employing carbon dioxide equilibration in that the analyte is added as a reagent
      to the water sample and exchanges oxygen isotopes with the water. In this
      procedure, however, the equilibration is more rapid and less sensitive to changes
      in ambient temperature, as the exchange is terminated by conversion of nitrite to
      nitrous oxide prior to analysis. The nitrous oxide is then analyzed using an on
      line purge and trap system coupled to an isotope ratio mass spectrometer. This
      method makes use of previously established methods for nitrite isotopic analysis
      and commercially available equipment. It has high throughput, relatively low
      standard deviation (0.1 per thousand or better), and small sample size (down to
      100 microL), is simple, and is applicable to both fresh- and seawater samples.

PMID- 16579624
TI  - Determination of carbon monoxide concentration and total pressure in gas cavities
      in the silica glass body of light bulbs by FT-IR spectrometry.
AB  - Fourier transform infrared (FT-IR) spectroscopy has been adapted to control the
      quality of light bulbs made from silica glass. Such light bulbs contain a
      molybdenum accessory which, if contaminated with carbon, during the melting
      procedure of bulb fabrication, can cause the production of carbon monoxide. This
      CO can be trapped in small gas cavities in the silica glass body of the bulb. A
      method has been developed for the detection of CO and the total pressure within
      these gas cavities by traditional FT-IR spectrometry using a spectral resolution
      of 0.5 cm(-1). The concentration of CO was determined by using a classical least
      squares (CLS) method, and the accuracy of concentration determination is reported
      for the case with sample and reference spectra recorded at different pressures.
      The total pressure in the cavities was established by two different methods:
      either by CLS fitting of reference spectra to sample spectra or fitting a Voigt
      line shape function to the spectral lines within the CO fundamental stretching
      band. In the latter method, the width of the lines was determined and pressure
      broadening coefficients are given and compared with high-resolution data from the
      literature. According to the measurements, 0.55-0.80 atm total pressure and 0.8
      4.0% (v/v) CO was determined in the gas cavities. This method can also be applied
      to determine the total pressure in similar enclosed spaces in which an
      appropriate indicator gas component exists.

PMID- 16579625
TI  - Identification of trichloroethanol visualized proteins from two-dimensional
      polyacrylamide gels by mass spectrometry.
AB  - Proteins visualized by 2,2,2-trichloroethanol (TCE) on two-dimensional
      electrophoresis gels are efficiently identified by matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and
      MS/MS. In a previous study, a method was developed that placed TCE in the
      polyacrylamide gel so that protein bands can be visualized without staining in
      less than 5 min. A visible fluorophore is generated by reaction of TCE with
      tryptophan that allows for protein visualization. In this study, MALDI-TOF MS and
      LC-MS/MS are used to identify randomly selected Escherichia coli proteins. The
      identification of TCE visualized proteins is compared to the identification of
      Coomassie brilliant blue (CBB) stained proteins from two-dimensional gel
      electrophoresis of E. coli proteins. This study demonstrated that TCE visualized
      proteins are compatible with protein identification by MALDI-TOF peptide mass
      fingerprinting. For 10 randomly selected spots, TCE visualization lead to
      statistically significant identification of 5 proteins and CBB visualization lead
      to identification of 6 proteins. TCE visualized proteins are also shown to be
      well suited for protein identification using LC-MS/MS. In 16 spots selected for
      MS/MS analysis, TCE samples lead to the identification of 79 peptides; while CBB
      samples lead to the identification of 65 peptides. TCE samples also supported the
      identification of more proteins. The low stoichiometry of labeling of tryptophan
      residues does not require inclusion of this modification for database searches.
      In addition to being a rapid visualization technique compatible with MS, TCE
      visualization utilizes rapid washing conditions for sample preparation of
      proteins spots excised from polyacrylamide gels.

PMID- 16579626
TI  - ZnO nanoparticle-modified infrared internal reflection elements for selective
      detection of volatile organic compounds.
AB  - In this study, we integrated zinc oxide nanomaterials, which possess a high
      surface-to-volume ratio and take part in specific interactions with organic
      functional groups, into infrared sensing devices to improve both the sensitivity
      and selectivity of the detection of volatile organic compounds (VOCs). An
      annealing method was developed to modify ZnO nanoparticles directly onto the
      surface of an IR internal reflection element. The ZnO nanoparticles produced this
      way are spherical (diameters, approximately 20 nm). When this modified sensing
      element was used to detect VOCs, intense IR signals for compounds bearing polar
      functional groups were observed. The conditions for preparing the ZnO
      nanoparticles for IR sensing of VOCs were optimized by varying such factors as
      the volume of the coating zinc solution, the calcination temperature, and
      calcination time. After mapping the IR signals obtained with respect to these
      factors, the optimal IR signal from this modified IR sensing element occurred
      when using 100 microL of zinc solution and performing the calcination at 400
      degrees C for at least 30 min. VOCs having different functional groups were used
      to characterize the behavior of the ZnO-modified sensing element; our results
      indicate that the selectivity of this device favors polar compounds. Based on
      detection of several polar VOCs, the results indicate that quantitative analysis
      is possible when using the ZnO nanoparticle-modified sensor; in some cases, the
      detection limit was below an injected sample volume of 0.5 nL (approximately 2.2
      ppm), with a linear regression coefficient (R2) above 0.99 when up to 0.3 microL
      of sample (approximately 1400 ppm) was injected to a 100 mL of sample cell.

PMID- 16579627
TI  - A sensitive method for the quantification of acrolein and other volatile
      carbonyls in ambient air.
AB  - Acrolein, an unsaturated aldehyde found in both indoor and outdoor air, is
      considered one of the greatest noncancer health risks of all organic air
      pollutants. Current methods for determining acrolein often employ sorbent-filled
      cartridges containing a carbonyl derivatizing agent (e.g.,
      dinitrophenylhydrazine). These methods are of limited use for unsaturated
      compounds due to the formation of unstable derivatives, coelution of similar
      compounds, long sample collection times, and ozone interferences that result in
      poor sensitivity, selectivity, and reproducibility. The goal of this research was
      to develop an analytical method for determining ppt concentrations of acrolein
      and other carbonyls in air with short sampling times (10 min). The method uses a
      mist chamber to collect carbonyls by forming water-soluble carbonyl-bisulfite
      adducts. The carbonyls are then liberated from the bisulfite, derivatized, and
      quantified by gas chromatography/electron capture negative ionization mass
      spectrometry. The method was applied to determine atmospheric acrolein
      concentrations at three sites in northern California reflecting hemispheric
      background concentrations, biogenic-dominated regions, and urban environments.
      The resulting acrolein concentrations were 0.056, 0.089, and 0.29 microg/m3,
      respectively, which are all above the EPA Reference Concentration of 0.02
      microg/m3. The minimum detection limit of 0.012 microg/m3 is below that of other
      published methods. Methacrolein, methyl vinyl ketone, crotonaldehyde, glyoxal,
      methyl glyoxal, and benzaldehyde were also quantified.

PMID- 16579628
TI  - Application of on-line electrochemical derivatization coupled with high
      performance liquid chromatography electrospray ionization mass spectrometry for
      detection and quantitation of (p-chlorophenyl)aniline in biological samples.
AB  - A rapid, sensitive, and specific assay for detection and quantitation of (p
      chlorophenyl)aniline (CPA) in biological samples was developed. The assay was
      established based on rapid electrochemical oxidation of CPA to a dimerized
      product (1.0 V vs Pd) with the enhanced detection sensitivity of electrospray
      mass spectrometer (ES/MS). A "head-to-tail" dimer ([M + H]+ at m/z 217) was
      exhibited as the predominant species after electrochemical conversion of CPA.
      Optimal detection sensitivity and specificity for the dimer of CPA that was
      present in the biological matrix (e.g., rat urine) were achieved through on-line
      electrochemistry (EC) coupled with high-performance liquid chromatography tandem
      mass spectrometry. No matrix-associated ion suppression was observed. The limit
      of detection (S/N approximately 6) was 20 ng/mL, and the limit of quantitation
      was 50 ng/mL. The calibration curve was exhibited to be quadratic over the range
      of 50-2000 ng/mL with r2 > 0.99 in various biological matrixes. The assay was
      validated and used to study the biotransformation of p-chlorophenyl isocyanate
      (CPIC) to CPA in rats administered intraperitoneally with CPIC (50 mg/kg). The
      present LC/EC/MS/MS assay of CPA brings important technical advantages to assist
      in the risk assessment of new chemical entities, which have the potential to
      produce anilines via biotransformation.

PMID- 16579629
TI  - Identification of rotenone-induced modifications in alpha-synuclein using
      affinity pull-down and tandem mass spectrometry.
AB  - Parkinson's disease is a movement disorder that results from a loss of
      dopaminergic neurons in the substantia nigra. The disease is characterized by
      mitochondrial dysfunction, oxidative stress, and the presence of "Lewy body"
      inclusions enriched with aggregated forms of alpha-synuclein, a presynaptic
      protein. Although alpha-synuclein is modified at various sites in Lewy bodies, it
      is unclear how sequence-specific posttranslational modifications modulate the
      aggregation of the protein in oxidatively stressed neurons. To begin to address
      this problem, we developed an affinity pull-down/mass spectrometry method to
      characterize the primary structure of histidine-tagged alpha-synuclein isolated
      from catecholaminergic neurons. Using this method, we mapped posttranslational
      modifications of alpha-synuclein from untreated neurons and neurons exposed to
      rotenone, an inhibitor of mitochondrial complex I. Various posttranslational
      modifications suggestive of oxidative damage or repair were identified in a
      region comprising a 20-residue stretch in the C-terminal part of the protein. The
      results indicate that alpha-synuclein is subject to discrete posttranslational
      modifications in neurons with impaired mitochondrial function. Our affinity pull
      down/mass spectrometry method is a useful tool to examine how specific
      modifications of alpha-synuclein contribute to neurologic disorders such as
      Parkinson's disease.

PMID- 16579630
TI  - Transition metal-peptide binding studied by metal-catalyzed oxidation reactions
      and mass spectrometry.
AB  - We have identified conditions that allow metal-catalyzed oxidation (MCO)
      reactions and mass spectrometry (MS) to correctly identify binding sites of first
      row transition metal ions to model peptides. This work extends the applicability
      of the MCO/MS method to metals other than Cu(II). When the appropriate reducing
      agent (ascorbate, 10 mM) and oxidizing agent concentrations (1 mM persulfate,
      atmospheric O2, or both) are used, metal-bound amino acids can be sufficiently
      and specifically oxidized for clear identification by MS. The MCO reactions with
      Mn(II), Fe(II), Co(II), and Ni(II) occur to lesser extents than with Cu(II), but
      oxidation is still extensive enough to allow easy identification of the metal
      bound residues. With the exception of aspartic acid, the known metal-binding
      amino acids of angiotensin I and bacitracin A are oxidized, while no oxidation is
      observed at nonbinding residues. Failure to oxidize aspartic acid is likely due
      to the relatively slow reactivity of its carboxylic acid side chain with reactive
      oxygen species, suggesting that the current MCO/MS protocol is transparent to
      such acidic residues. Overall, this study indicates that, just as is possible for
      Cu(II), the MCO/MS method should be suitable for determining the Mn(II)-, Fe(II)
      , Co(II)-, and Ni(II)-binding sites of metalloproteins.

PMID- 16579631
TI  - New guidelines for delta13C measurements.
AB  - Consistency of delta13C measurements can be improved 39-47% by anchoring the
      delta13C scale with two isotopic reference materials differing substantially in
      13C/12C. It is recommended that delta13C values of both organic and inorganic
      materials be measured and expressed relative to VPDB (Vienna Peedee belemnite) on
      a scale normalized by assigning consensus values of -46.6 per thousand to L-SVEC
      lithium carbonate and +1.95 per thousand to NBS 19 calcium carbonate.
      Uncertainties of other reference material values on this scale are improved by
      factors up to two or more, and the values of some have been notably shifted: the
      delta13C of NBS 22 oil is -30.03 per thousand.

PMID- 16579632
TI  - Single-walled carbon nanotube paper as a sorbent for organic vapor
      preconcentration.
AB  - Single-walled carbon nanotubes were examined as an adsorptive material for a
      thermally desorbed preconcentrator for organic vapors. The nanotubes were
      processed into a paper form and packed into a metal tube for flow-through
      sampling. Adsorbed vapors were released by a temperature-programmed desorption
      method and detected downstream with a flexural plate wave vapor sensor. The
      tested vapors, methyl ethyl ketone, toluene, and dimethyl methylphosphonate, were
      released from the packed column at different temperatures. The vapors were
      retained more strongly than previously observed for the widely used Tenax porous
      polymer, indicating a significant affinity of the single walled nanotubes for
      organic vapors.

PMID- 16579633
TI  - Magnetic nanoparticles applied in electrochemical detection of controllable DNA
      hybridization.
AB  - Electrochemical detection of hybridized DNA strands was achieved with a magnetic
      nanoparticle modified electrode and the commonly used electrochemical couple
      K3[Fe(CN)6]/K4[Fe(CN)6]. The detection proved to be fast and very simple.
      Furthermore, magnetic nanoparticles could be employed to control the DNA
      hybridization process. An inhibited or an enhanced degree of hybridizing could be
      produced.

PMID- 16579634
TI  - Redox-sensitive copolymer: a single-component pH sensor.
AB  - A novel redox-active copolymer has been developed, capable of sensing pH. The
      polymer incorporates the redox-active but pH-insensitive vinylferrocene moiety as
      the internal reference signal, alongside the redox-active and pH-sensitive
      vinylanthracene moiety. The anthracene moiety undergoes a Nernstian potential
      shift with pH. The various monomer and homopolymer components have been examined
      in turn and the electrochemical response of the polymer characterized.
      Furthermore, the pH response was found to be stable over a wide temperature
      range.

PMID- 16579635
TI  - Improving the performance of glutamate microsensors by purification of ascorbate
      oxidase.
AB  - Enzyme-based biosensors have the potential to directly detect extracellular
      concentrations of glutamate in brain tissue with a high spatial and temporal
      resolution. To optimize their analytical performance, much attention has been
      paid to the architectural construction of these biosensors. In particular, the
      coupling of enzymes to the electrode surface has received much interest, which
      has resulted in many (derivatives of) first-, second-, and third-generation type
      of biosensors. However, it is remarkable that in the literature little attention,
      if any, has been paid to the influence of the quality of the enzyme itself on the
      analytical performance of a biosensor. Previously we have reported that different
      batches of ascorbate oxidase significantly altered the performance of our
      glutamate microsensor.(1) In this note, it is shown that a simple enzyme
      purification procedure as buffer exchange leads to a more uniform enzyme quality
      and also significantly improves the reproducibility and performance of the
      microsensor. In our opinion, this is an important observation and of general
      interest for the construction of enzyme-based biosensors.

PMID- 16579636
TI  - Templated one-step synthesis of compositionally encoded nanowire tags.
AB  - Multimetal nanowire tags, with distinct encoding patterns, have been prepared
      using a one-step templated electrodeposition from solutions containing different
      concentrations of various metal ions. Such synthesis of compositionally encoded
      nanowire tags is substantially faster and simpler than the preparation of striped
      nanowires based on sequential plating steps from different metal solutions and
      leads to high identification accuracy. The alloy nanowire preparation route leads
      to a high coding capacity with a large number of distinguishable voltammetric
      signatures, reflecting the predetermined composition of the metal mixture plating
      solution (and hence the nanowire composition). Factors influencing the
      identification accuracy are evaluated using three-metal (In, Pb, Bi) alloy
      nanowires, and the relative advantages and disadvantages of the new route are
      discussed.

PMID- 16579637
TI  - Analysis of intact tissue by intermediate-pressure MALDI on a linear ion trap
      mass spectrometer.
AB  - The use of an intermediate-pressure matrix-assisted laser desorption/ionization
      (IP-MALDI) source working at 0.17 Torr on a linear ion trap (LIT) was
      investigated for the analysis of tissue specimens, in particular, spinal cord
      sections. MALDI, with 2,5-dihydroxybenzoic acid (DHB) as the matrix, was employed
      for the detection of phospholipids. The matrix was applied to the tissue using
      electrospray to avoid analyte migration. The results indicate that analyzing
      tissue specimens at nontraditional MALDI vacuum pressures is possible. Coupling
      MALDI to an LIT permits the use of MSn, which is critical for the ability to
      identify compounds desorbed directly from tissue specimens. Using MSn, ions
      detected from m/z 600-1000 were characterized as phosphatidlycholines, PC.
      Specifically, using tandem MS, PC ions could be classified as either [M + H]+ or
      [M + Na]+ because the fragmentation patterns of protonated and sodiated
      phosphatidlycholines follow different pathways.

PMID- 16579638
TI  - Adenovirus vector-mediated gene transfer into stem cells.
AB  - Stem cells, including embryonic stem (ES) cells, mesenchymal stem cells (MSCs),
      and hematopoietic stem cells (HSCs), are defined by their capacity for self
      renewal and multilineage differentiation. Efficient gene transfer into stem cells
      is essential for the basic research in developmental biology and for therapeutic
      applications in gene-modified regenerative medicine. Adenovirus (Ad) vectors,
      based on Ad type 5, can efficiently and transiently introduce the exogenous gene
      into many cell types via the primary receptor, coxsackievirus, and adenovirus
      receptor (CAR). However, some kinds of stem cells, such as MSCs and HSCs, cannot
      be efficiently transduced with conventional Ad vectors based on Ad serotype 5
      (Ad5), because of the lack of CAR expression. To overcome this problem, fiber
      modified Ad vectors and an Ad vector based on another serotype of Ad have been
      developed. Here, we review the advances in the development of Ad vectors suitable
      for stem cells and discuss their application in basic biology and clinical
      medicine.

PMID- 16579639
TI  - Increased intracellular targeting to airway cells using octaarginine-coated
      liposomes: in vitro assessment of their suitability for inhalation.
AB  - Delivery of macromolecular drugs to airway cells after inhalation can be limited
      by rapid clearance, in vivo degradation, and poor intracellular targeting.
      Liposome carriers offer an effective method of improving drug stability, but
      conventional liposomes have limited intracellular targeting capacity and are
      cleared rapidly by the lungs. Further modification is required to improve
      liposome-cell interaction and intracellular targeting. Therefore, we proposed
      conjugating three arginine-rich membrane translocating peptides, namely, HIV-TAT,
      Antennapedia, and octaarginine, to neutral liposomes as a biocompatible
      alternative to cationic lipids for intracellular delivery of macromolecules to
      airway cells. Conjugation did not significantly affect liposome stability, and
      each system was nebulized to produce aerosols of mean aerodynamic diameter < 1.5
      microm. The peptides caused a significant (p < 0.05) increase in liposome-airway
      cell association compared to untagged liposomes and to DOTAP liposomes. Up to 30%
      of the peptide-conjugated liposomes added were bound and internalized (via a
      temperature-dependent, endocytic process) after just 2 h. The novel carriers all
      delivered encapsulated dextrans rapidly and efficiently to the cytoplasm of Calu
      3 cells. Once internalized by the cells, the modified carriers localize for the
      most part in the cytoplasm with only a small amount of nuclear localization.
      These peptide-conjugated liposomes were significantly (p < 0.05) less toxic than
      DOTAP liposomes with octaarginine-coated liposomes the least toxic. These
      systems, particularly octaarginine-coated liposomes, offer many advantages for
      drug delivery to airway epithelial cells including increased stability, improved
      cell binding, and cell uptake with an improved toxicity profile.

PMID- 16579641
TI  - Nonviral gene delivery by tetraamino fullerene.
AB  - A fullerene derivative bearing two diamino side chains binds to a plasmid vector
      DNA, either 4 or 40 kbp in size, delivers it to mammalian cells on incubation,
      and leads to expression of the encoded gene either transiently or stably. The
      initial physicochemical investigations upon DNA-binding and protective properties
      of various fullerene compounds against nuclease led us to identify the tetraamino
      fullerene as an ideal candidate to probe the new concept of fullerene-mediated
      gene delivery to mammalian cells. Studies on transient and stable transfection of
      COS-1 cells using green fluorescent protein and luciferase reporter genes
      revealed several useful properties of the fullerene transfection as compared with
      the conventional lipid-based transfection method, including much higher
      efficiency of stable transfection and ability to transfect confluent cells.
      Chemical and biological studies suggested that the cell uptake of the
      fullerene/DNA complex takes place by an endocytosis mechanism and that the DNA
      internalized by endosomes is protected by the fullerene against enzymatic
      digestion. The stiffness of the fullerene/DNA complex may play some role in the
      success of the fullerene method.

PMID- 16579640
TI  - Alteration of genomic responses to doxorubicin and prevention of MDR in breast
      cancer cells by a polymer excipient: pluronic P85.
AB  - Polymer therapeutics has emerged as a new clinical option for the treatment of
      human diseases. However, little is known about pharmacogenetic responses to drugs
      formulated with polymers. In this study, we demonstrate that a formulation
      containing the block copolymer Pluronic P85 and antineoplastic drug doxorubicin
      (Dox) prevents the development of multidrug resistance in the human breast
      carcinoma cell line, MCF7. Specifically, MCF7 cells cultured in the presence of
      Pluronic were unable to stably grow in concentrations of Dox that exceeded 10 ng
      of Dox/mL of culture medium. In sharp contrast, MCF7 cells cultured in the
      absence of the block copolymer resulted in the selection and stable growth of
      cells that tolerated a 1000 times higher concentration of the drug (10 000 ng of
      Dox/mL of culture medium). Detailed characterization of the isolated sublines
      demonstrated that those cells selected in the polymer-drug formulation did not
      show amplification of the MDR1 gene, likely resulting in their high sensitivity
      to the drug. Conversely, cells selected with Dox alone showed an elevated level
      in the expression of the MDR1 gene along with a corresponding increase in the
      expression level of the drug efflux transporter, Pgp, and likely contributing to
      the high resistance of the cells to Dox. Global analysis of the expression
      profiles of 20K genes by DNA microarray revealed that the use of Pluronic in
      combination with Dox drastically changed the direction and magnitude of the
      genetic response of the tumor cells to Dox and may potentially enhance
      therapeutic outcomes. Overall, this study reinforces the need for a thorough
      assessment of pharmacogenomic effects of polymer therapeutics.

PMID- 16579642
TI  - Reservoir-type microcapsules prepared by the solvent exchange method: effect of
      formulation parameters on microencapsulation of lysozyme.
AB  - A new microencapsulation technique based on the solvent exchange method was
      implemented using an ultrasonic atomizer system to encapsulate a protein drug in
      mild conditions. The reservoir-type microcapsules encapsulating lysozyme as a
      model protein were prepared by inducing collisions between the aqueous droplets
      containing lysozyme and the droplets of organic solvent with dissolved
      poly(lactic acid-co-glycolic acid) (PLGA). The main focus of the study was to
      examine formulation variables on the size and the encapsulation efficiency of the
      formed microcapsules. The formulation variables examined were concentrations of
      mannose in the aqueous cores, NaCl in the aqueous collection medium, and PLGA in
      organic solvent. The mean diameter of the microcapsules ranged from 40 microm to
      100 microm. Smaller microcapsules showed lower encapsulation efficiencies. The
      resulting microcapsules released native lysozyme in a sustained manner, and the
      release rate was dependent on the formulation conditions, such as the
      concentration and molecular weight of the polymer used. The solvent exchange
      method does not induce lysozyme aggregation and loss of its biological activity.
      The solvent exchange method, implemented by the ultrasonic atomizer system,
      provides an effective tool to prepare reservoir-type microcapsules for delivering
      proteins.

PMID- 16579643
TI  - Encapsulation of submicrometer-sized 2-methoxyestradiol crystals into polymer
      multilayer capsules for biological applications.
AB  - A facile approach has been developed to encapsulate submicrometer-sized drug
      crystals into polymer multilayer capsules produced by sequential deposition of
      polymers onto the drug particle surfaces. 2-Methoxyestradiol (2-ME) is a
      hydrophobic metabolite of 17-beta estradiol, which has been demonstrated as a
      potential anticancer agent. It was selected as a model drug and was formulated
      into submicrometer-sized particles through fine milling followed by intense
      sonication in the presence of dipalmitoyl-dl-(R)-phosphatidylcholine (DPPC). The
      reserved positive charges on the 2-ME crystal surface by DPPC enhanced the water
      solubility of the particles and subsequent self-assembly of dextran sulfate (DS)
      and dextran (DN) multilayers through hydrogen bonding and physical adsorption.
      Upon the exposure of the drug capsules to ethanol, hollow DS/DN multilayer
      polymer shells can be formed. The encapsulation process and hollow polymer
      multilayer shell formation were confirmed by confocal laser scanning microscopy
      (CLSM) and transmission electron microscopy (TEM), while the surface morphology
      of the formed drug capsules was investigated using scanning electron microscopy
      (SEM). In vitro studies show that the inhibitory effect of the formed 2-ME
      capsules is the same as that of the conventional formulation of 2-ME in a
      concentrated ethanol solution, as demonstrated by dramatic changes in cell
      morphology and significantly decreased viability of target cells. We also
      demonstrate that the change of the outermost layer of the drug capsules does not
      significantly influence its bioactivity. The presented strategy to encapsulate
      submicrometer-sized hydrophobic drug particles is expected to provide a general
      pathway to fabricate drug capsules for various biological applications.

PMID- 16579644
TI  - Novel polymer micelles prepared from chitosan grafted hydrophobic palmitoyl
      groups for drug delivery.
AB  - Chitosan-based polymer micelles have a splendid outlook for drug delivery owing
      to the interesting properties, abundance, and low cost of chitosan. A new method
      of preparation of water-soluble N-palmitoyl chitosan (PLCS) which can form
      micelles in water is developed in this paper. The preparation of PLCS was carried
      out by swollen chitosan coupling with palmitic anhydride in dimethyl sulfoxide
      (DMSO). The degree of substitution (DS) of PLCS was in the range of 1.2-14.2%,
      and the critical aggregation concentration (CAC) of PLCS micelles was in the
      range of 2.0 x 10(-3) to 37.2 x 10(-3) mg/mL. The properties of PLCS micelles
      such as encapsulation capacity and controlled release ability of hydrophobic
      model drug ibuprofen (IBU) were evaluated. Experimental results indicated that
      the loading capacity (LC) of PLCS was approximately 10%. The drug release
      strongly depended on pH and temperature: low pH and high temperature accelerated
      drug release markedly. Moreover, the IR, 1H NMR, and TEM of PLCS, IBU-loaded
      PLCS, and a PLCS-IBU physical mixture have been measured to show that IBU is
      loaded by PLCS micelles.

PMID- 16579645
TI  - Sulfonyl-containing nucleoside phosphotriesters and phosphoramidates as novel
      anticancer prodrugs of 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP).
AB  - A series of sulfonyl-containing 5-fluoro-2'-deoxyuridine (FdU) phosphotriester
      and phosphoramidate analogues were designed and synthesized as anticancer
      prodrugs of FdUMP. Stability studies have demonstrated that these compounds
      underwent pH dependent beta-elimination to liberate the corresponding nucleotide
      species with half-lives in the range of 0.33-12.23 h under model physiological
      conditions in 0.1 M phosphate buffer at pH 7.4 and 37 degrees C. Acceleration of
      the elimination was observed in the presence of human plasma. Compounds with an
      FdUMP moiety (4-9) were considerably more potent than those without (1-3) as well
      as 5-fluorouracil (5-FU) against Chinese hamster lung fibroblasts (V-79 cells) in
      vitro. Addition of thymidine (10 microM) reversed the growth inhibition
      activities of only 5-FU and the compounds with an FdUMP moiety, but had no effect
      on those without. These results are consistent with thymidylate synthase as the
      target of the prodrugs.

PMID- 16579646
TI  - Distribution of immunoglobulin Fab fragment conjugated with HIV-1 REV peptide
      following intravenous administration in rats.
AB  - HIV-1 REV peptide (positions 34-50) is well-known as a cell-permeating peptide.
      In this study, we investigated the distribution of Fab fragment of immunoglobulin
      conjugated with REV peptide (REV-Fab) following intravenous administration in
      rats, and compared with those of the native Fab fragment (nFab). Radioiodinated
      REV-Fab or nFab ((125)I-REV-Fab or (125)I-nFab, respectively) was given in a
      single intravenous dose of 2 mg/kg (3 MBq/kg). Total radioactive and TCA
      insoluble radioactive concentrations in blood, whole-body autoradiography (ARG),
      and urinary excretion rates were assayed following administration. Regarding
      blood and plasma, total radioactive and TCA-insoluble radioactive concentrations
      for (125)I-REV-Fab were remarkably lower than those for (125)I-nFab. In the whole
      body ARG at 4 h after administration, (125)I-REV-Fab produced remarkably higher
      radioactivity in the adrenal gland, spleen, and liver, compared to (125)I-nFab.
      Regarding urinary excretion rates, approximately 70% of the radioactive dose was
      excreted in the form of a low-molecular-weight component by 24 h after
      administration for both samples. (125)I-REV-Fab may penetrate quickly from blood
      to adrenal gland, spleen, liver, and other tissues after intravenous
      administration to rats, and then did not stay in situ and was digested and
      excreted mostly via the renal route by 24 h. With these features, cell-permeating
      peptides are expected to help the development of new antibody pharmaceuticals.

PMID- 16579647
TI  - Membrane transduction of oligoarginine in HeLa cells is not mediated by
      macropinocytosis.
AB  - The mechanism in which small cationic oligopeptides are able to reach the cytosol
      of cells is controversial. Macropinocytosis has been recently suggested as a
      major mechanism for internalization of these peptides. In this report, the
      involvement of macropinocytosis on cytosolic localization of oligoarginine was
      quantitatively investigated in HeLa cells. Using a method which allows for the
      separate measurement of cytosolic versus vesicular oligopeptide, the results show
      that neither macropinosome nor filopodia formation correlates with cytosolic
      delivery of oligoarginine. Additionally, unlike macropinocytosis, the cytosolic
      delivery of oligoarginine was not inhibited by incubation at 16 degrees C, or by
      treatment with amiloride. Oligoarginine treatment does not contribute to leakage
      from endocytic vesicles, indicating the lack of endosomolytic properties.
      Finally, the amount of oligoarginine found in the cytosol was not substantially
      increased after coincubation with EGF, a known stimulator of macropinocytosis.
      Taken together, these data indicate that membrane transduction of oligoarginine
      occurs separately from macropinocytosis in HeLa cells.

PMID- 16579648
TI  - Stochastic models for prodrug targeting. 1. Diffusion of the efflux drug.
AB  - In modeling prodrug targeting using the stochastic approach, we first modeled
      diffusion of the efflux drug. Drug efflux is one of the major reasons for the
      failure of prodrug strategy: the active agent is pumped out the membrane
      ("efflux"), causing an insufficient amount to be delivered to the targeted sites
      and thus diminishing the efficacy of chemotherapy. Because the biological body is
      a nonlinear nonequilibrium complex system, the molecular transport taking place
      in vivo often showed stochasticity. The model described here for diffusion of the
      efflux drug is basically a diffusion process with reflecting/absorbing boundary
      conditions, divided into two distinctive regions with one allowing the particles
      to jump to the origin as a result of efflux pumping. We study discrete time birth
      death Markov chain and compute the time-dependent spatial probability density
      function (PDF) of particles. The results showed that the jumping probability,
      although small, has a significant impact on the evolution of PDF of the efflux
      drug. The implications of this model were discussed.

PMID- 16579649
TI  - Effects of dietary supplements on the space radiation-induced reduction in total
      antioxidant status in CBA mice.
AB  - In the present study, the total antioxidant status was used as a biomarker to
      evaluate oxidative stress induced by proton, HZE-particle and gamma radiation in
      CBA mice. The results demonstrated that the plasma level of TAS was significantly
      decreased (P < 0.05) in CBA mice after exposure to a 50-cGy dose of radiation
      from HZE particles or a 3-Gy dose of radiation from protons or gamma rays. Diet
      supplementation with Bowman-Birk Inhibitor Concentrate (BBIC), L-selenomethionine
      (L-SeM), or a combination of N-acetyl cysteine, sodium ascorbate, co-enzyme Q10
      (CoQ10), alpha-lipoic acid, L-SeM and vitamin E succinate could partially or
      completely prevent the reduction in the plasma level of TAS in CBA mice exposed
      to proton or HZE-particle radiation. The selected antioxidant combination with or
      without CoQ10 has a comparable protective effect on the gamma-radiation-induced
      drop in TAS in CBA mice. These results indicate that BBIC, L-SeM and the selected
      antioxidant combinations may serve as countermeasures for space radiation-induced
      adverse biological effects.

PMID- 16579650
TI  - Effect of low-level radiation on the death of male germ cells.
AB  - Hormetic and adaptive responses induced by low-level radiation in hematopoietic
      and immune systems have been observed, as shown by stimulatory effects on cell
      growth and resistance to subsequent radiation-induced cytogenetic damage.
      However, in terms of cell death by apoptosis, the effects of low-level radiation
      are controversial: Some studies showed decreased apoptosis in response to low
      level radiation while others showed increased apoptosis. This controversy may be
      related to the radiation doses or dose rates and also, more importantly, to the
      cell types. Testes are one of the most radiosensitive organs. The loss of male
      germ cells after exposure to ionizing radiation has been attributed to apoptosis.
      In the present study, the effects of low-level radiation at doses up to 200 mGy
      on mouse male germ cells in terms of apoptosis and the expression of apoptosis
      related proteins were examined at different times after whole-body exposure of
      mice to low-level radiation. In addition, the effect of pre-exposure to low-level
      radiation on subsequent cell death induced by high doses of radiation was
      examined to explore the possibility of low-level radiation-induced adaptive
      response. The results showed that low-level radiation in the dose range of 25-200
      mGy induced significant increases in apoptosis in both spermatogonia and
      spermatocytes, with the maximal effect at 75 mGy. The increased apoptosis is most
      likely associated with Trp53 protein expression. Furthermore, 75 mGy low-level
      radiation given pre-irradiation led to an adaptive response of seminiferous germ
      cells to subsequent high-level radiation-induced apoptosis. These results suggest
      that low-level radiation induces increased apoptosis in male germ cells but also
      induces a significant adaptive response that decreases cell death after a
      subsequent high-dose irradiation.

PMID- 16579651
TI  - Mechanisms of apoptosis induction and cell cycle regulation in irradiated
      leukemia U937 cells and enhancement by arsenic trioxide.
AB  - Apoptosis is a common mode of cell death after exposure of tumor cells to
      radiation and/or chemotherapy. The factors that determine the rate of induction
      of apoptosis are generally related to the functioning of cell cycle checkpoints.
      In the present study, we investigated the involvement of several genes in cell
      cycle redistribution and induction of apoptosis in U937 cells after low and high
      doses of radiation. Activation of CDC2 was observed after both low and high doses
      of radiation in U937 cells that underwent apoptosis. Expression of CDK2, CDC2 and
      cyclin A was induced rapidly in the process of radiation-induced apoptosis. In
      addition, we investigated the use of a clinically relevant dose of radiation to
      promote As2O3-induced apoptosis in U937 cells. We found that combining radiation
      and As2O3 may be a new and more effective means of cancer treatment.

PMID- 16579653
TI  - Hsf1-mediated stress response can transiently enhance cellular radioresistance.
AB  - To elucidate how the heat-shock transcription factor 1 (Hsf1)-mediated stress
      response affects cellular radioresistance, mouse embryo fibroblasts with Hsf1
      gene knockout (Hsf1(-/-) cells) or with normal wild-type Hsf1 expression (Hsf1
      wild-type cells) were preconditioned by heating (43 degrees C, 30 min) without or
      with quercetin (an inhibitor of Hsf1) and then exposed to gamma radiation (4 or 6
      Gy). Some cell samples were infected with virus-based vectors to overexpress the
      constitutively active (mutant) form of Hsf1 or individual heat-shock proteins
      (Hsps). The heat preconditioning transiently up-regulated the Hsp levels in Hsf1
      wild-type cells and significantly improved their postirradiation survival; these
      effects could be abolished by quercetin or simulated (without preheating) by the
      Hsf1 overexpression. In contrast, no enhanced radioresistance was found in heat
      preconditioned Hsf1(-/-) cells that were unable to trigger Hsf1-mediated Hsp
      induction after heating. However, when the constitutively active Hsf1 was
      overexpressed in Hsf1(-/-) cells, the latter accumulated stress-inducible Hsps
      and became more radioresistant like heat-preconditioned Hsf1 wild-type cells. The
      overexpression of Hsp70 or/ and Hsp27 also enhanced radioresistance of both cell
      cultures. Thus the preirradiation stress response resulting in the intracellular
      Hsp accumulation can improve survival of severely irradiated mammalian cells.

PMID- 16579652
TI  - The involvement of calcium and MAP kinase signaling pathways in the production of
      radiation-induced bystander effects.
AB  - Much evidence now exists regarding radiation-induced bystander effects, but the
      mechanisms involved in the transduction of the signal are still unclear. The
      mitogen-activated protein kinase (MAPK) pathways have been linked to growth
      factor-mediated regulation of cellular events such as proliferation, senescence,
      differentiation and apoptosis. Activation of multiple MAPK pathways such as the
      ERK, JNK and p38 pathways have been shown to occur after exposure of cells to
      radiation and a variety of other toxic stresses. Previous studies have shown
      oxidative stress and calcium signaling to be important in radiation-induced
      bystander effects. The aim of the present study was to investigate MAPK signaling
      pathways in bystander cells exposed to irradiated cell conditioned medium (ICCM)
      and the role of oxidative metabolism and calcium signaling in the induction of
      bystander responses. Human keratinocytes (HPV-G cell line) were irradiated (0.005
      5 Gy) using a cobalt-60 teletherapy unit. The medium was harvested 1 h
      postirradiation and transferred to recipient HPV-G cells. Phosphorylated forms of
      p38, JNK and ERK were studied by immunofluorescence 30 min-24 h after exposure to
      ICCM. Inhibitors of the ERK pathway (PD98059 and U0126), the JNK pathway
      (SP600125), and the p38 pathway (SB203580) were used to investigate whether
      bystander-induced cell death could be blocked. Cells were also incubated with
      ICCM in the presence of superoxide dismutase, catalase, EGTA, verapamil,
      nifedipine and thapsigargin to investigate whether bystander effects could be
      inhibited because of the known effects on calcium homeostasis. Activated forms of
      JNK and ERK proteins were observed after exposure to ICCM. Inhibition of the ERK
      pathway appeared to increase bystander-induced apoptosis, while inhibition of the
      JNK pathway appeared to decrease apoptosis. In addition, reactive oxygen species,
      such as superoxide and hydrogen peroxide, and calcium signaling were found to be
      important modulators of bystander responses. Further investigations of these
      signaling pathways may aid in the identification of novel therapeutic targets.

PMID- 16579654
TI  - Gene expression analysis of a human lymphoblastoma cell line exposed in vitro to
      an intermittent 1.9 GHz pulse-modulated radiofrequency field.
AB  - This study was designed to determine whether radiofrequency (RF) fields of the
      type used for wireless communications could elicit a cellular stress response. As
      general indicators of a cellular stress response, we monitored changes in proto
      oncogene and heat-shock protein expression. Exponentially growing human
      lymphoblastoma cells (TK6) were exposed to 1.9 GHz pulse-modulated RF fields at
      average specific absorption rates (SARs) of 1 and 10 W/kg. Perturbations in the
      expression levels of the proto-oncogenes FOS, JUN and MYC after exposure to sham
      and RF fields were assessed by real-time RT-PCR. In addition, the transcript
      levels of the cellular stress proteins HSP27 and inducible HSP70 were also
      monitored. We demonstrated that transcript levels of these genes in RF-field
      exposed cells showed no significant difference in relation to the sham treatment
      group. However, concurrent positive (heat-shock) control samples displayed a
      significant elevation in the expression of HSP27, HSP70, FOS and JUN. Conversely,
      the levels of MYC mRNA were found to decline in the positive (heat-shock)
      control. In conclusion, our study found no evidence that the 1.9 GHz RF-field
      exposure caused a general stress response in TK6 cells under our experimental
      conditions.

PMID- 16579655
TI  - A comparative evaluation of radiation-induced DNA damage using real-time PCR:
      influence of base composition.
AB  - To study the radiosensitivity of DNA segments at the open reading frame (gene)
      level, real-time PCR was used to analyze DNA damages induced by ionizing
      radiation. After irradiation (1, 3 and 5 kGy) of genomic DNA purified from
      Salmonella typhimurium, real-time PCR based on SYBR Green fluorescence and
      melting temperature was performed using various primer sets targeting the rfbJ,
      rfaJ, rfaB, hilD, ssrB, pipB, sopD, pduQ, eutG, oadB, ccmB and ccmA genes. The
      ccmA and ccmB genes, which existed as two copies on the chromosome and had a high
      GC content ( approximately 70%), showed much lower radiosensitivities than the
      other genes tested, particularly at 5 kGy; this distinctive feature was seen only
      when the genes were located on the chromosome, regardless of copy number. Our
      results reinforce the concept that gene sensitivity to ionizing radiation depends
      on the base composition and/or the spatial localization of the gene on the
      chromosome.

PMID- 16579656
TI  - A novel approach to DNA damage assessments: measurement of the thymine glycol
      lesion.
AB  - A different approach to the measurement of DNA damage has been developed based on
      the fact that many lesions can be excised from DNA in the form of modified
      dinucleoside monophosphates. Liquid chromatography-tandem mass spectrometry (LC
      MS/MS) is used in conjunction with isotopically labeled internal standards to
      quantify the lesion. The method has several advantages, including high
      sensitivity for the detection of dinucleoside monophosphates. The method was
      applied to the measurement of the 5,6-dihydroxy-5,6-dihydrothymine (thymine
      glycol) lesion in the DNA of mouse fibroblast cells exposed in culture to various
      treatments including ionizing radiation, UVC light and buthionine sulfoximine
      (BSO), an inhibitor of glutathione synthesis. The application of the method to
      the measurement of other DNA lesions is discussed.

PMID- 16579657
TI  - Singlet oxygen-induced DNA damage.
AB  - Singlet oxygen, hydrogen peroxide, hydroxyl radical and hydrogen peroxide are the
      reactive oxygen species (ROS) considered most responsible for producing oxidative
      stress in cells and organisms. Singlet oxygen interacts preferentially with
      guanine to produce 8-oxo-7,8-dihydroguanine and spiroiminodihydantoin. DNA damage
      due to the latter lesion has not been detected directly in the DNA of cells
      exposed to singlet oxygen. In this study, the singlet oxygen-induced lesion was
      isolated from a short synthetic oligomer after exposure to UVA radiation in the
      presence of methylene blue. The lesion could be enzymatically excised from the
      oligomer in the form of a modified dinucleoside monophosphate. Using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS), the singlet oxygen lesion was
      detected in the form of modified dinucleoside monophosphates in double-stranded
      DNA and in the DNA of HeLa cells exposed to singlet oxygen. Pentamer containing
      the singlet oxygen-induced lesion and an isotopic label was synthesized as an
      internal standard for quantifying the lesion and served as well as for correcting
      for losses of product during sample preparation.

PMID- 16579658
TI  - Effective cross sections for production of single-strand breaks in plasmid DNA by
      0.1 to 4.7 eV electrons.
AB  - We determined effective cross sections for production of single-strand breaks
      (SSBs) in plasmid DNA [pGEM 3Zf(-)] by electrons of 10 eV and energies between
      0.1 and 4.7 eV. After purification and lyophilization on a chemically clean
      tantalum foil, dry plasmid DNA samples were transferred into a high-vacuum
      chamber and bombarded by a monoenergetic electron beam. The amount of the
      circular relaxed DNA in the samples was separated from undamaged molecules and
      quantified using agarose gel electrophoresis. The effective cross sections were
      derived from the slope of the yield as a function of exposure and had values in
      the range of 10(-15)- 10(-14) cm2, giving an effective cross section of the order
      of 10(-18) cm2 per nucleotide. Their strong variation with incident electron
      energy and the resonant enhancement at 1 eV suggest that considerable damage is
      inflicted by very low-energy electrons to DNA, and it indicates the important
      role of pi* shape resonances in the bond-breaking process. Furthermore, the fact
      that the energy threshold for SSB production is practically zero implies that the
      sensitivity of DNA to electron impact is universal and is not limited to any
      particular energy range.

PMID- 16579659
TI  - Microdosimetric model for the induction of cell killing through medium-borne
      signals.
AB  - Microbeam, medium-transfer and low-dose experiments have demonstrated that
      intercellular signals can initiate many of the same biological events and
      processes as direct exposure to ionizing radiation. These phenomena cast doubt on
      cell-autonomous modes of action and the linear, no-threshold carcinogenesis
      paradigm. To account for the effects of intercellular signals, new approaches are
      needed to relate dosimetric quantities to the emission and processing of signals
      by irradiated and unirradiated cells. In this paper, microdosimetric principles
      are used to develop a stochastic model to relate absorbed dose to the emission
      and processing of cell death signals by unirradiated cells. Our analyses of
      published results of medium transfer experiments performed using HPV-G human
      keratinocytes suggest that the emission of death signals is a bi-exponential
      function of dose with a distinct plateau in the 5- to 100-mGy range. However, the
      emission of death signals by HPV-G cells may not become fully saturated until the
      absorbed dose becomes larger than 0.6 Gy. Similar saturation effects have been
      observed in microbeam and medium-transfer experiments with other mammalian cell
      lines. The model predicts that the cell-killing effect of medium-borne death
      signals decreases exponentially as the absorbed dose becomes small compared to
      the frequency-mean specific energy per radiation event.

PMID- 16579660
TI  - Biophysical mechanisms: a component in the weight of evidence for health effects
      of power-frequency electric and magnetic fields.
AB  - Comparatively high exposures to power-frequency electric and magnetic fields
      produce established biological effects that are explained by accepted mechanisms
      and that form the basis of exposure guidelines. Lower exposures to magnetic
      fields (< 1 microT average in the home) are classified as "possibly carcinogenic"
      on the basis of epidemiological studies of childhood leukemia. This
      classification takes into consideration largely negative laboratory data. Lack of
      biophysical mechanisms operating at such low levels also argues against
      causality. We survey around 20 biophysical mechanisms that have been proposed to
      explain effects at such low levels, with particular emphasis on plausibility: the
      principle that to produce biological effects, a mechanism must produce a "signal"
      larger than the "noise" that exists naturally. Some of the mechanisms are
      impossible, and some require specific conditions for which there is limited or no
      evidence as to their existence in a way that would make them relevant to human
      exposure. Others are predicted to become plausible above some level of field. We
      conclude that effects below 5 microT are implausible. At about 50 microT, no
      specific mechanism has been identified, but the basic problem of implausibility
      is removed. Above about 500 microT, there are established or likely effects from
      accepted mechanisms. The absence of a plausible biophysical mechanism at lower
      fields cannot be taken as proof that health effects of environmental electric and
      magnetic fields are impossible. Nevertheless, it is a relevant consideration in
      assessing the overall evidence on these fields.

PMID- 16579661
TI  - Photo-induced hole transfer from base to sugar in DNA: relationship to primary
      radiation damage.
AB  - This work presents the hypothesis that photo-excitation of G.+ in DNA and model
      systems results in the same electronic states expected from direct ionization of
      the sugar phosphate backbone and that these states lead to specific sugar
      radicals on the DNA sugar phosphate backbone. As evidence we show that visible
      photo-excitation of guanine cation radicals (G.+) in the dinucleoside phosphate
      TpdG results in high yields (about 85%) of deoxyribose sugar radicals at the C1'
      and C3' sites. Further, we have calculated transition energies of hole transfer
      from G.+ in TpdG using time-dependent density functional theory (TD-DFT) at the
      B3LYP/6-31G(d) level in gas phase as well as in a solvated environment. These
      calculations clearly predict that visible excitation of G.+ in TpdG causes
      transitions from only inner-shell filled molecular orbitals (MOs) to the singly
      occupied molecular orbital (SOMO) that effectively result in hole transfer from
      guanine either to the sugar phosphate backbone or to the adjacent base, thymine.
      The hole transfer is followed by rapid deprotonation from the sugar to form C1'
      and C3' radicals. These experimental and theoretical results are in agreement
      with our previously published experimental and theoretical results that photo
      excitation of G.+ results in high yields of deoxyribose sugar radicals in DNA,
      guanine deoxyribonucleosides and deoxyribonucleotides. Photo-excitation of G.+
      therefore provides a convenient method to produce and study sugar radicals that
      are expected to be formed in gamma-irradiated DNA systems unencumbered by the
      many other pathways involved in direct ionization.

PMID- 16579662
TI  - High-LET ion radiolysis of water: visualization of the formation and evolution of
      ion tracks and relevance to the radiation-induced bystander effect.
AB  - Ionizing radiation-induced bystander effects, commonly observed in cell
      populations exposed to high-linear energy transfer (LET) radiations, are
      initiated by damage to a cellular molecule which then gives rise to a toxic
      signal exported to neighboring cells not directly hit by radiation. A major goal
      in studies of this phenomenon is the identification of this initial radiation
      induced lesion. Liquid water being the main constituent of biological matter,
      reactive species produced by water radiolysis in the cellular environment are
      likely to be major contributors to the induction of this lesion. In this context,
      the radiation track structure is of crucial importance in specifying the precise
      location and identity of all the radiolytic species and their subsequent
      signaling or damaging effects. We report here Monte Carlo track structure
      simulations of the radiolysis of liquid water by four different impacting ions
      1H+, 4He2+, 12C6+ and 20Ne10+, with the same LET ( approximately 70 keV/ microm).
      The initial radial distribution profiles of the various water decomposition
      products (eaq(-), *OH, H*, H2 and H2O2) for the different ions considered are
      presented and discussed briefly in the context of track structure theory. As an
      example, the formation and temporal evolution of simulated 24 MeV 4He2+ ion
      tracks (LET approximately 26 keV/microm) are reported for each radiolytic species
      from 1 ps to 10 micros. The calculations reveal that the ion track structure is
      completely lost by approximately 1 micros.

PMID- 16579665
TI  - Age-related effects in sequential motor learning.
AB  - BACKGROUND AND PURPOSE: When learning multi-element movement sequences,
      participants organize individual elements into subsequences. Imposing this type
      of structure on the elements leads to the efficient production of sequences
      because the processing of all but the first elements in a subsequence can be
      completed prior to their execution. The primary purpose of this study was to
      determine whether older adults organize lengthy movement sequences with the same
      efficiency as young adults. SUBJECTS AND METHODS: Participants were young adults
      (N=8, 19-23 years of age) and older adults (N=8, 65-68 years of age). The task
      required participants to move a lever as quickly as possible to targets
      sequentially projected on a tabletop. At various stages during practice, random
      practice blocks were inserted between the repeated sequence blocks. Repeated and
      random sequence retention tests were administered after 24 hours. RESULTS: The
      results indicated that the young adults performed the repeated sequences
      substantially faster than the older adults and that this difference increased
      over practice. On the retention tests, there were no differences in response time
      for the random sequence blocks, but the young performers were substantially
      faster than the older performers when repeated sequences were used. No
      differences were detected in the interview or on the recognition (chi
      square=1.22, P>.05) and completion (chi square=0.89, P>.05) tests designed to
      determine explicit or implicit knowledge of the sequences. DISCUSSION AND
      CONCLUSION: Analysis of the sequence structure indicated that the older adults
      did not organize their responses into subsequences as effectively as the young
      adults. The failure of older adults to optimally organize movement sequences may
      contribute to the overall slowing of sequential movement production.

PMID- 16579667
TI  - Reporting ethical protections in physical therapy research.
AB  - BACKGROUND AND PURPOSE: Efforts to make physical therapy more evidence based have
      increased demand for human participants, raising concerns for their safety and
      welfare. This study examined how often research articles in physical therapy
      journals report basic ethical protections. METHODS: We carried out a
      retrospective audit of research articles in 6 physical therapy journals between
      1996 and 2001. RESULTS: Of 806 articles reviewed, 48% documented both research
      ethics committee approval and informed consent. Articles reporting clinical
      interventions had the highest reported rate (64%) of both protections. Articles
      reporting qualitative methods, chart reviews, and case reports had the lowest
      rates of documentation of both requirements: 30%, 17%, and 11%, respectively.
      Reported rates of both requirements in vulnerable populations were 55% for
      children, 48% for students, and 33% for employees. Twenty-six percent of articles
      included confidentiality assurances. Case reports were most likely and chart
      reviews were least likely to mention confidentiality: 88% and 8%, respectively.
      DISCUSSION AND CONCLUSION: There is no uniform editorial policy among physical
      therapy journals for reporting basic ethical requirements. Physical therapy
      journals should standardize ethical protections and make documentation of
      compliance a prerequisite of publication.

PMID- 16579666
TI  - A high-intensity functional weight-bearing exercise program for older people
      dependent in activities of daily living and living in residential care
      facilities: evaluation of the applicability with focus on cognitive function.
AB  - BACKGROUND AND PURPOSE: Knowledge concerning the applicability and the effect of
      high-intensity exercise programs is very limited for older people with severe
      cognitive and physical impairments. The primary aim of this study was to evaluate
      the applicability of a high-intensity functional weight-bearing exercise program
      among older people who are dependent in activities of daily living and living in
      residential care facilities. A second aim was to analyze whether cognitive
      function was associated with the applicability of the program. SUBJECTS: The
      subjects were 91 older people (mean age=85.3 years, SD=6.1, range=68-100) who
      were dependent in personal activities of daily living and randomly assigned to
      participate in an exercise intervention. Their mean score for the Mini-Mental
      State Examination (MMSE) was 17.5 (SD=5.0, range=10-29). METHODS: A high
      intensity functional weight-bearing exercise program was performed in groups of 3
      to 7 participants who were supervised by physical therapists. There were 29
      exercise sessions over 13 weeks. Attendance, intensity of lower-limb strength and
      balance exercises, and occurrence and seriousness of adverse events were the
      outcome variables in evaluating the applicability of the program. RESULTS: The
      median attendance rate was 76%. Lower-limb strength exercises with high intensity
      were performed in a median of 53% of the attended exercise sessions, and balance
      exercises with high intensity were performed in a median of 73% of the attended
      exercise sessions. The median rate of sessions with adverse events was 5%. All
      except 2 adverse events were assessed as minor and temporary, and none led to
      manifest injury or disease. No significant differences were observed in
      applicability when comparing participants with dementia and participants without
      dementia. In addition, there was no significant correlation between applicability
      and the MMSE score. DISCUSSION AND CONCLUSION: The results suggest that a high
      intensity functional weight-bearing exercise program is applicable for use,
      regardless of cognitive function, among older people who are dependent in
      activities of daily living, living in residential care facilities, and have an
      MMSE score of 10 or higher.

PMID- 16579669
TI  - Effect of therapeutic exercise on gait speed in community-dwelling elderly
      people: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: Inconsistent research findings make it unclear whether
      therapeutic exercise improves gait speed in community-dwelling elderly people.
      Using meta-analytical procedures, we examined the effect of therapeutic exercise
      on changing gait speed in community-dwelling older adults and the effect of type,
      intensity, and dose of therapeutic exercise on gait speed. METHOD: Studies were
      retrieved using a comprehensive database search. Two independent reviewers
      determined study eligibility based on inclusion criteria, rated study quality,
      and extracted information on study methods, design, intervention, and results.
      Data were combined to obtain an overall effect size, its 95% confidence interval,
      and a measure of significance. In addition, analyses to characterize the clinical
      relevance of the findings were performed. RESULTS: One hundred seventeen studies
      were evaluated, with 24 studies (n=1,302 subjects) meeting the inclusion criteria
      for habitual gait speed and 18 studies (n=752 subjects) meeting the inclusion
      criteria for fast gait speed. Therapeutic exercise--or, more specifically,
      strength training and combination training (aerobic plus other exercise)--had
      significant effects (r=.145, P=.017; r=.176, P=.002, respectively) on habitual
      gait speed. High-intensity (effort expended by subjects) exercise and high-dosage
      (frequency and duration of exercise sessions) intervention also had a significant
      effect (r=.184, P=.001; r=.190, P=.001, respectively) on gait speed, whereas
      there was no effect for moderate- and low-intensity exercise or for low-dosage
      exercise. No exercise intervention affected fast gait speed in this analysis.
      DISCUSSION AND CONCLUSION: The results provide support for the belief that
      therapeutic exercise can improve gait speed in community-dwelling elderly people
      and that intensity and dosage are important contributing factors. The relatively
      weak correlation found between therapeutic exercise and gait speed merits further
      study.

PMID- 16579668
TI  - Factors affecting physical activity behavior in urban adults with arthritis who
      are predominantly African-American and female.
AB  - BACKGROUND AND PURPOSE: Physical activity and exercise play a critical role in
      the management of arthritis. Understanding the factors affecting physical
      activity and exercise behavior is a necessary first step toward identifying the
      needs of, and intervention strategies for, people with arthritis. The purpose of
      this study was to identify factors affecting physical activity and exercise
      behavior in urban subjects with osteoarthritis (OA) and rheumatoid arthritis
      (RA). SUBJECTS: Seventy-two consecutive subjects were recruited from the
      rheumatology clinic at a large urban public hospital. The sample was
      predominantly African American (92%), female (87%), and not working (90%). The
      subjects' average age was 60.9 years (SD=13.9, range=30-90). METHODS: Time per
      day spent sitting or lying down and time per week spent in exercise, leisure, and
      household activities were determined by individual interview. Self-efficacy,
      outcome expectations, disability, pain, body mass index, and social support were
      measured as possible explanatory factors. RESULTS: The average daily total
      activity time was 3.1 hours. Household and leisure activities accounted for 85%
      of that time. Explanatory factors for physical activity behavior were not the
      same for subjects with OA and RA, despite similar between-group characteristics.
      Self-efficacy was present in all of the significant explanatory models.
      DISCUSSION AND CONCLUSION: The results indicate that factors that affect physical
      activity behavior among urban and predominantly African-American adults are
      dependent upon the type of physical activity and are different for people with OA
      and RA. Self-efficacy was the most consistent explanatory factor.

PMID- 16579670
TI  - Use of the physical performance test to assess preclinical disability in subjects
      with asymptomatic carotid artery disease.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine whether
      subjects with asymptomatic carotid artery stenosis and occlusion demonstrate
      deficits in physical performance compared with a comparison group. These deficits
      may indicate that a person is demonstrating preclinical disability. SUBJECTS:
      Seventy-one subjects with no known disease and 39 subjects with asymptomatic
      carotid artery stenosis of moderate and severe degrees or with occlusion were
      included. METHODS: Physical performance was assessed with the 9-item and 7-item
      versions of the Physical Performance Test (PPT). Individual tasks also were timed
      for the subjects with disease. RESULTS: There were significant differences
      between the comparison group and the subjects with carotid artery stenosis on the
      9-item PPT (P<.00) and on the 7-item PPT (P<.03). Subjects with asymptomatic
      carotid artery stenosis and occlusion demonstrated less than optimal performance
      on the PPT (9-item PPT, mean=27 of 36; 7-item PPT, mean=21 of 28). Subjects with
      moderate stenosis were the slowest in performing the task of simulated eating.
      DISCUSSION AND CONCLUSION: Subjects with asymptomatic carotid artery stenosis and
      occlusion exhibited changes in function, as indicated by their performance on the
      PPT relative to that of a comparison group. This finding may be indicative of
      preclinical disability, indicating that these people are symptomatic. This
      indication may affect the medical and surgical options that can be considered for
      their care.

PMID- 16579671
TI  - Resting position variables at the shoulder: evidence to support a posture
      impairment association.
AB  - BACKGROUND AND PURPOSE: A relationship between posture and impairment at the
      shoulder is theorized, but not supported by evidence. It is proposed that posture
      and impairment are not directly related, but linked by movement dysfunction. The
      purpose of this analysis was to explore the relationships among posture,
      pectoralis minor muscle length, and movement alterations at the shoulder.
      SUBJECTS: Subjects who were asymptomatic for shoulder pathology were divided into
      2 groups of 25 subjects each based on normalized pectoralis minor muscle resting
      length. METHODS: Scapula orientation, thoracic kyphosis, and pectoralis minor
      muscle lengths were measured, and ratios and indexes of postural variables were
      calculated. All variables were analyzed for correlations and group differences.
      RESULTS: Significant group differences were demonstrated for several posture
      variables, including thoracic spine kyphosis and scapular internal rotation. The
      distance from the sternal notch to the coracoid process demonstrated the highest
      correlation with pectoralis minor muscle length. DISCUSSION AND CONCLUSION: The
      findings indicate a relationship between posture and pectoralis minor muscle
      length and support a proposed model linking posture, an anatomical variable,
      movement dysfunction, and impairment.

PMID- 16579672
TI  - Early rehabilitation following surgical fixation of a femoral shaft fracture.
AB  - BACKGROUND AND PURPOSE: The purpose of this case report is to describe the
      outcome of a patient following fixation of a midshaft femur fracture and an
      evaluation-based, immediate-weight-bearing approach to rehabilitation. CASE
      DESCRIPTION: The patient was a 28-year-old male manual laborer whose left femur
      was fractured in a head-on motor vehicle accident. The patient was treated with
      internal fixation of the left femur by use of an antegrade intramedullary nail.
      Following surgery, impairments in range of motion, knee extensor and hip abductor
      strength, and gait were observed. Intervention focused on immediate weight
      bearing and early progression of strengthening to address the observed
      impairments. OUTCOMES: All of the patient's impairments improved, and he was able
      to return to work as a manual laborer within 6 months. DISCUSSION: Immediate
      weight bearing with early strengthening activities following surgical correction
      of a midshaft femur fracture may result in early resolution of impairments and
      functional limitations and decreased disability.

PMID- 16579673
TI  - Use of botulinum toxin type A in children with cerebral palsy.

PMID- 16579676
TI  - Tissue-engineered bone repair of goat-femur defects with osteogenically induced
      bone marrow stromal cells.
AB  - Tissue engineering can generate bone tissue and has been shown to provide a
      better means of repairing weight-bearing bone defect. Previous studies, however,
      have heretofore been limited to the use of nonosteogenically induced bone marrow
      stromal cells (BMSCs) or the application of slow-degradation scaffolds. In this
      study, weight-bearing bone was engineered using osteogenically induced BMSCs. In
      addition, coral was used as a scaffold material, due to its proper degradation
      rate for the engineering and repair of a goat femur defect. A 25 mm long defect
      was created at the middle of the right femur in each of 10 goats. The rates of
      defect repair were compared in an experimental group of ten goats receiving
      implants containing osteogenically induced BMSCs and in the control group of
      goats (n = 10) receiving just coral cylinders. In the experimental group, bony
      union was observed by radiographic and gross view at 4 months, and engineered
      bone was further remodeled into newly formed cortexed bone at 8 months. There was
      increased gray density of radiographic rays in the repaired area, which was
      significantly different (p < 0.05) from that of the control group. H&E staining
      demonstrated that trabecular bone was formed at 4 months. Moreover, irregular
      osteon was observed at 8 months. Most importantly, the tissue-engineered bone
      segment revealed a similarity to the left-side normal femur in terms of bend load
      strength and bend rigidity, showing no significant difference (p > 0.05). In
      contrast, the coral cylinders of the control group showed no bone formation.
      Furthermore, almost complete resorption of the carrier had occurred, being
      evident at 2 months in the control group. H&E staining demonstrated that a small
      amount of residual coral particle was surrounded by fibrous tissue at 4 months
      whereas the residues disappeared at 8 months. Based on these results, we conclude
      that engineered bone from osteogenically induced BMSCs and coral can ideally heal
      critical-sized segmental bone defects in the weight-bearing area of goats.

PMID- 16579674
TI  - Association of genetic factors with selected measures of physical performance.

PMID- 16579675
TI  - Increased prevalence of diabetes mellitus in a rural Greek population.
AB  - INTRODUCTION: Diabetes mellitus (DM) is becoming a modern epidemic due to the
      high prevalence of obesity and physical inactivity. Previous studies in Greece in
      urban and mixed urban and rural populations, reported a prevalence of DM of less
      than 3%. However data concerning the prevalence of DM in exclusively rural areas
      of Greece are lacking. The purpose of this study was to investigate the
      prevalence of DM in a representative rural area of Greece. METHODS: The group
      studied consisted of the resident population of the villages Saint Demetreus,
      Adami and Metohi of the district of Argolida, Greece, according to the 2001 Greek
      Census. In total, 880 subjects, aged 1-99 years (410 males [46.6%] mean age [+/-
      standard deviation, SD] 46.7 +/- 26 yrs, 470 females-mean age [+/- SD] 48.2 +/-
      24.3 years) were screened for the presence of DM. Body mass index (BMI), waist to
      hip ratio (WHR), personal and family history were recorded at baseline. After an
      overnight fast, blood samples were drawn for the determination of plasma glucose
      (FPG) and serum lipid profile. In the case of FPG >126 mg/dL a second
      determination was performed one week later. Subjects with FPG <126 mg/dL on
      repeated test, and those with FPG between 110 and 126 mg/dL, were invited to
      undergo an oral glucose tolerance test. Diagnosis of DM was based on the 1999 WHO
      criteria. RESULTS: The prevalence of DM was 7.8 % (95% CI: 5.9-12.5), with known
      diabetics being 5.3% of the population and undiagnosed diabetes being 2.5%. No
      significant differences were detected between males and females (7.1% vs 7.6%,
      p>0.05). There was a significant increase in the prevalence of DM with increasing
      age (age 41-50 years: 6.4% vs 71-80 years 14.1%, p<0.05). Impaired glucose
      tolerance was diagnosed in 3.9%, while impaired fasting glucose was diagnosed in
      1.9%. Furthermore, the prevalence of obesity (BMI>30 kg/m2<) was 20.8%, while
      central obesity (WHR >0.90 males, >0.85 in females) was observed in 63%. Age,
      obesity, family history of DM, arterial hypertension and elevated triglyceride
      levels were significantly associated with the presence of DM (p<0.001).
      CONCLUSION: The prevalence of DM has significantly increased in the rural
      population of Greece. Age, hypertension, obesity, family history of diabetes and
      elevated triglyceride levels were significantly associated with prevalent
      diabetes. These subjects should be a primary target for preventive intervention
      strategies.

PMID- 16579677
TI  - Nano-featured scaffolds for tissue engineering: a review of spinning
      methodologies.
AB  - Tissue engineering is a multidisciplinary field that is rapidly emerging as a
      promising new approach in the restoration and reconstruction of imperfect
      tissues. In this approach, scaffolds play a pivotal role in supporting the cells
      to accommodate and guide their growth into a specific tissue; therefore,
      designing scaffolds that are favorable to cellular growth is of great importance.
      Electrospinning is a straightforward, cost-effective, and versatile technique
      that has been applied recently for the fabrication of nano-featured scaffolds
      suitable for tissue engineering. By mimicking a natural extracellular matrix, it
      offers many advantages over conventional scaffold methodologies. This paper
      reviews the current state of art of designing nanostructure scaffolds by using
      the electrospinning technique. Furthermore, an overview of this technique and its
      spinning mechanism is described, with special attention to areas of interest to
      the readers.

PMID- 16579678
TI  - Mechano-active scaffold design based on microporous poly(L-lactide-co-epsilon
      caprolactone) for articular cartilage tissue engineering: dependence of porosity
      on compression force-applied mechanical behaviors.
AB  - An essential component of functional articular cartilage tissue engineering is a
      mechano-active scaffold, which responds to applied compression stress and causes
      little permanent deformation. As the first paper of a series on mechano-active
      scaffold-based cartilage tissue engineering, this study focused on mechanical
      responses to various modes of loading of compression forces and subsequent
      selection of mechano-active scaffolds from the biomechanical viewpoint. Scaffolds
      made of elastomeric microporous poly(L-lactide-co-epsilon-caprolactone) (PLCL)
      with open-cell structured pores (300 approximately 500 microm) and with different
      porosities ranging from 71 to 86% were used. The PLCL sponges and rabbit
      articular cartilage tissue were subjected to compression/unloading tests (0.1 and
      0.005 Hz) at 5 kPa, and stress relaxation tests at 10, 30, and 50% strain. The
      measurements of the maximum strain under loading and residual strain under
      unloading for compression tests and the maximum stress and equilibrium stress in
      the stress relaxation test showed that the lower the porosity, the closer the
      mechanical properties are to those of native cartilage tissue. Among the PLCL
      sponges, the sponge with 71% porosity appears to be a suitable cartilage
      scaffold.

PMID- 16579679
TI  - A collagen-glycosaminoglycan scaffold supports adult rat mesenchymal stem cell
      differentiation along osteogenic and chondrogenic routes.
AB  - Adult mesenchymal stem cells have the proclivity to differentiate along multiple
      lineages giving rise to new bone, cartilage, muscle, or fat. Collagen, a normal
      constituent of bone, provides strength and structural stability and is therefore
      a potential candidate for use as a substrate on which to engineer bone and
      cartilage from their respective mesenchymal-derived precursors. In this study, a
      collagen- glycosaminoglycan scaffold was used to provide a suitable three
      dimensional (3-D) environment on which to culture adult rat mesenchymal stem
      cells and induce differentiation along the osteogenic and chondrogenic lineages.
      The results demonstrate that adult rat mesenchymal stem cells can undergo
      osteogenesis when grown on the collagen-glycosaminoglycan scaffold and stimulated
      with osteogenic factors (dexamethasone, ascorbic acid, beta-glycerophosphate), as
      evaluated by the temporal induction of the bone-specific proteins, collagen I and
      osteocalcin, and subsequent matrix mineralization. The osteogenic factors were
      coupled to activation of the extracellular-regulated protein kinase (ERK), and
      this kinase was found to play a role in the osteogenic process. As well as
      supporting osteogenesis, when the cell-seeded scaffold was exposed to
      chondrogenic factors (dexamethasone and TGF-1beta), collagen II immunoreactivity
      was increased, providing evidence that the scaffold can also provide a suitable 3
      D environment that supports chondrogenesis.

PMID- 16579680
TI  - Fluid flow increases type II collagen deposition and tensile mechanical
      properties in bioreactor-grown tissue-engineered cartilage.
AB  - A novel parallel-plate bioreactor has been designed to apply a consistent level
      of fluid flow-induced shear stress to tissue-engineered articular cartilage in
      order to improve the matrix composition and mechanical properties and more nearly
      approximate to that of native tissue. Primary bovine articular chondrocytes were
      seeded into the bioreactor at high densities (1.7 x 10(6) cell/cm2) without a
      scaffold and cultured for two weeks under static, no-flow conditions. A mean
      fluid flow-induced shear stress of 1 dyne/cm2 was then applied continuously for 3
      days. The application of flow produced constructs with significantly (p < 0.05)
      higher amounts of total collagen (via hydroxyproline) and specifically type II
      collagen (via ELISA) (25.3 +/- 2.5% and 22.1 +/- 4.7% of native tissue,
      respectively) compared to static controls (22.4 +/- 1.7% and 9.5 +/- 2.3%,
      respectively). Concurrently, the tensile Young's modulus and ultimate strength
      were significantly increased in flow samples (2.28 +/- 0.19 MPa and 0.81 +/- 0.07
      MPa, respectively) compared to static controls (1.55 +/- 0.10 MPa and 0.62 +/-
      0.05 MPa, respectively). This study suggests that flow-induced shear stresses
      and/or enhanced mass transport associated with the hydrodynamic environment of
      our novel bioreactor may be an effective functional tissue-engineering strategy
      for improving matrix composition and mechanical properties in vitro.

PMID- 16579681
TI  - A knitted, fibrin-covered polycaprolactone scaffold for tissue engineering of the
      aortic valve.
AB  - State-of-the-art tissue engineered heart valves are not strong enough to
      withstand aortic blood pressure levels. When a strong and slowly degrading
      scaffold is used, the starting position of valvular tissue engineering is a
      stronger valve and seeded cells are allowed more time to create a strong
      extracellular matrix. A polycaprolactone knitted patch with leaflets was
      developed as a valvular scaffold. It was sutured into a tube and covered with
      fibrin gel. The opening and closing behavior and leakage of knitted scaffolds
      without cells were studied and compared to those of stentless porcine valves. An
      MTT test was performed on polycaprolactone and fibrin. A loading device was
      developed to study the durability of the knitted scaffold. The scaffold showed
      proper opening and it showed coaptation upon closing, but a 39 +/- 3% (n = 3)
      leakage, compared to a 8 +/- 1% (n = 3) leakage of tested porcine valves. MTT
      tests showed that polycaprolactone and fibrin are biocompatible materials.
      Durability testing of the knitted scaffold (n = 1) did not show rupture after ten
      million loading cycles. A tissue engineering process that includes cell culture
      will have to show whether this scaffold, besides mechanically reliable and
      biocompatible, is suitable to lead to a functional, nonregurgitant, durable
      aortic valve.

PMID- 16579682
TI  - Bone regeneration by modified gene-activated matrix: effectiveness in segmental
      tibial defects in rats.
AB  - Gene-activated matrix (GAM) is a matrix, such as collagen-containing plasmid
      vector, that encodes a protein to stimulate tissue regeneration. In the original
      GAM system, gene transfer efficiency was extremely low. We have recently reported
      that modifying GAM with calcium-phosphate precipitates (CaP) enhances the
      efficiency of gene transfer. The purpose of this study was to evaluate the
      effects of our modified GAM on tissue regeneration. We prepared critical size
      segmental bone defects in rat tibiae and transplanted GAM consisting of bovine
      atelocollagen and expression plasmid vector (bmp2), which encodes human BMP2,
      with or without CaP. The tibiae were later examined radiographically,
      histologically, and mechanically. Implantation of bmp2-CaP-collagen at 12 microg
      bmp2 bridged the bone defect at 4 weeks, and the strength of the bone was
      comparable to that of an intact tibia at 6 weeks. Implantation of bmp2-collagen
      at the same dose of bmp2 bridged the defect to a smaller extent. Neither collagen
      alone nor vacant vector-CaP-collagen bridged the defect. These results indicate
      that our modified GAM with CaP has the potential to be effective in tissue
      regeneration at lower plasmid DNA doses than used in previous studies.

PMID- 16579683
TI  - Long-term survival and growth of pulsatile myocardial tissue grafts engineered by
      the layering of cardiomyocyte sheets.
AB  - Recently researchers have attempted to bioengineer three-dimensional (3-D)
      myocardial tissues using cultured cells in order to repair damaged hearts. In
      contrast to the conventional approach of seeding cells onto 3-D biodegradable
      scaffolds, we have explored a novel technology called cell sheet engineering,
      which layers cell sheets to construct functional tissue grafts. In this study, in
      vivo survival, function, and morphology of myocardial tissue grafts were
      examined. Neonatal rat cardiomyocytes were noninvasively harvested as contiguous
      cell sheets from temperature-responsive culture dishes simply by reducing the
      culture temperature. Cardiomyocyte sheets were then layered and transplanted into
      the subcutaneous tissues of athymic rats. The microvasculature of the grafts was
      rapidly organized within a few days with macroscopic graft beatings observed 3
      days after transplantation and preserved up to one year. Size, conduction
      velocity, and contractile force of transplanted grafts increased in proportion to
      the host growth. Histological studies showed characteristic structures of heart
      tissue, including elongated cardiomyocytes, well-differentiated sarcomeres, and
      gap junctions within the grafts. In conclusion, long-term survival and growth of
      pulsatile myocardial tissue grafts fabricated by layering cell sheets were
      confirmed, demonstrating that myocardial tissue regeneration based on cell sheet
      engineering may prove useful for permanent myocardial tissue repair.

PMID- 16579684
TI  - Constructing a tissue-engineered ureter using a decellularized matrix with
      cultured uroepithelial cells and bone marrow-derived mononuclear cells.
AB  - This study investigated the efficacy of the ureteral decellularized matrix (UDM)
      as a scaffold material for a tissue-engineered ureter, and the effect of bone
      marrow-derived mononuclear cells (BM-MNC) on the neovascularization of the
      scaffold. Canine ureters were treated with deoxycholic acid to remove all cells.
      Uroepithelial cells (UEC) were obtained from canine bladders, cultured, and then
      seeded onto the inner surface of the UDM before transplantation into the
      subcutaneous space of nude mice or the omentum of nude rats. The cultured UECs
      began showing vacuolar degeneration 3 days after transplantation and gradually
      disappeared thereafter. To facilitate neovascularization in the implant, BM-MNCs
      were seeded around the UDM before transplantation. This facilitated the survival
      of the UECs, which formed three to five cellular layers after 14 days. The mean
      microvessel density was significantly increased in tissues seeded with BM-MNCs.
      However, cell-tracking experiments revealed that the increased number of
      capillaries in the experimental group was not due to the direct differentiation
      of transplanted endothelial progenitor cells. Our results demonstrate that the
      UDM is a useful scaffold for a tissue-engineered ureter, especially when seeded
      with BM-MNCs to enhance angiogenesis.

PMID- 16579685
TI  - The basement membrane component of biologic scaffolds derived from extracellular
      matrix.
AB  - The extracellular matrix (ECM) has been successfully used as a scaffold for
      constructive remodeling of multiple tissues in both preclinical studies and in
      human clinical applications. The basement membrane is a specialized form of the
      ECM that supports and facilitates the growth of epithelial cell populations. The
      morphology and the molecular composition of the ECM, including the basement
      membrane, vary depending upon the organ from which the ECM is harvested and the
      methods by which it is processed for use as a medical device. Processing steps,
      such as decellularization, lyophilization, disinfection, and terminal
      sterilization, may affect the morphology and composition of an ECM scaffold,
      including, but not limited to, the integrity of a basement membrane complex. The
      present study evaluated the presence and integrity of a basement membrane complex
      in processed ECM derived from three different tissues: the urinary bladder, small
      intestine, and liver. Immunohistochemical determination of the presence and
      localization of three basement membrane molecules, collagen IV, laminin, and
      collagen VII, was conducted for each ECM scaffold. Scanning electron microscopy
      (SEM) was used to further explore the surface ultrastructure of selected ECM
      scaffolds. The effect of a surface basement membrane presence upon the pattern of
      in vitro growth of two separate cell types, NIH 3T3 fibroblasts and human
      microvascular endothelial cells (HMEC), was also evaluated for each ECM scaffold.
      Results showed that the only intact basement membrane complex was found on the
      luminal surface of the ECM derived from the urinary bladder and that the basement
      membrane was an effective barrier to penetration of the scaffold by the seeded
      cells. We conclude that the urinary bladder ECM but not the small intestine- or
      liver-derived ECM contains a surface with composition and morphology consistent
      with that of an intact basement membrane complex, that the basement membrane
      complex can survive processing, and that the basement membrane structure can
      modulate in vitro cell growth patterns.

PMID- 16579686
TI  - Chondrogenic differentiation of mesenchymal stem cells isolated from patients in
      late adulthood: the optimal conditions of growth factors.
AB  - There is a controversy about the capacity of the mesenchymal stem cells (MSCs)
      from aged individuals to proliferate and differentiate into cartilage. The
      purpose of this study was to investigate the optimal condition to culture human
      MSCs from the aged individuals (>50 years) for cartilage tissue engineering. We
      tested the hypothesis that effective proliferation and chondrogenesis can be
      achieved with human MSCs from aged individuals under appropriate conditions. To
      investigate the best condition for proliferation, MSCs were cultured in medium
      containing four concentrations subsets (0, 0.05, 0.5, 5 ng/mL) of recombinant
      human TGF-beta2 and FGF-2, either with or without fetal calf serum. The cell
      numbers were counted 0, 1, 3, and 7 days after growth factors were given. For the
      induction of chondrogenesis in 3-dimensional (3-D) culture, cells were cultured
      in pellets with chondrogenic medium containing combinations of various growth
      factors. After 4 weeks of culture, the pellets were fixed and evaluated with
      Safranin-O staining for proteoglycan and immunohistochemical staining for type II
      collagen. RT-PCR was also performed for the mRNAs of type I collagen, type II
      collagen, and cartilage oligomeric protein (COMP). In a monolayer culture, TGF
      beta2 in concentrations of 0.5 and 5 ng/mL caused significant reduction in cell
      number irrespective of the presence of serum. FGF-2 of 5 ng/mL most effectively
      increased cell number even in the absence of serum. In a pellet culture,
      remarkable chondrocyte-like differentiation of cells was induced around the
      peripheral areas of a pellet with 5 ng/mL of TGF-beta2, accompanied by increased
      proteoglycan and type II collagen production. The addition of 100 ng/mL of IGF-I
      induced notable increase in proteoglycan contents. The results of RT-PCR mirrored
      those of histological studies. This study shows that an effective proliferation
      and chondrogenesis may be obtained with proper combinations of growth factors and
      mesenchymal stem cells from aged individuals.

PMID- 16579688
TI  - Characterization of tissue-engineered scaffolds microfabricated with PAM.
AB  - PAM (pressure-activated microsyringe) is a new microfabrication technique that
      allows the fabrication of two- and three-dimensional scaffolds with a well
      defined geometry using polymers soluble in volatile solvents. In this study,
      polymeric scaffolds were realized with four different polymers--PCL, PLLA, PLGA,
      and a blend of PCL and PLLA--and with three different geometries-square grids,
      hexagonal grids, and octagonal grids. The scaffolds were characterized in terms
      of porosity, hydrophilicity, cell adhesion, and their mechanical properties. An
      analysis of the measured data shows that the physical and mechanical properties
      of the scaffold depend on its geometry and line width, both of which are easily
      modulated using PAM.

PMID- 16579689
TI  - Optimized chondrogenesis of ATCD5 cells through sequential regulation of oxygen
      conditions.
AB  - The objective of this study was to determine the optimal oxygen conditions for
      chondrogenesis of ATDC5 mouse embryonic stem cells. Chondrogenesis was induced by
      addition of insulin and the cells were then cultured at different oxygen
      concentrations ranging from 1 to21%. At 2- to 3-day intervals, chondrocyte
      specific extracellular matrix (ECM) production was monitored. Furthermore, the
      transcription of collagen II, an early-phase marker, and collagen X, a marker of
      hypertrophic conversion, was followed by real-time RT-PCR. Low oxygen
      concentrations between 1 and 9% inhibited chondrogenic conversion, as evidenced
      by reduced glycosaminoglycan deposition in the ECM in a manner proportional to
      the degree of hypoxia. Cells cultured at oxygen concentrations of 12 and 15%
      underwent a faster and higher degree of early-phase chondrogenesis when compared
      to control cells cultured at ambient air (21% O2). For the hypertrophic
      conversion of the ATDC5 cells, all degrees of hypoxia inhibited collagen X
      expression in a dose-dependent manner. Short-term culturing of the ATDC5 cells
      for 6 to 8 days at 12% oxygen with subsequent culturing at 21% for the remainder
      of the experiment resulted in maximal production of major ECM components,
      including collagen II and glycosaminoglycans. It is thus possible to modify in
      vitro chondrogenesis through modulation of the gas-phase composition.

PMID- 16579687
TI  - Sustained release of TGFbeta3 from PLGA microspheres and its effect on early
      osteogenic differentiation of human mesenchymal stem cells.
AB  - Despite the widespread role of transforming growth factor-beta3 (TGFbeta3) in
      wound healing and tissue regeneration, its long-term controlled release has not
      been demonstrated. Here, we report microencapsulation of TGFbeta3 in poly-d-l
      lactic-co-glycolic acid (PLGA) microspheres and determine its bioactivity. The
      release profiles of PLGA-encapsulated TGFbeta3 with 50:50 and 75:25 PLA:PGA
      ratios differed throughout the experimental period. To compare sterilization
      modalities of microspheres, bFGF was encapsulated in 50:50 PLGA microspheres and
      subjected to ethylene oxide (EO) gas, radio-frequency glow discharge (RFGD), or
      ultraviolet (UV) light. The release of bFGF was significantly attenuated by UV
      light, but not significantly altered by either EO or RFGD. To verify its
      bioactivity, TGFbeta3 (1.35 ng/mL) was control-released to the culture of human
      mesenchymal stem cells (hMSC) under induced osteogenic differentiation. Alkaline
      phosphatase staining intensity was markedly reduced 1 week after exposing hMSC
      derived osteogenic cells to TGFbeta3. This was confirmed by lower alkaline
      phosphatase activity (2.25 +/- 0.57 mU/mL/ng DNA) than controls (TGFbeta3- free)
      at 5.8 +/- 0.9 mU/mL/ng DNA (p < 0.05). Control-released TGFbeta3 bioactivity was
      further confirmed by lack of significant differences in alkaline phosphatase upon
      direct addition of 1.35 ng/mL TGFbeta3 to cell culture (p > 0.05). These findings
      provide baseline data for potential uses of microencapsulated TGFbeta3 in wound
      healing and tissue-engineering applications.

PMID- 16579690
TI  - Localization of type VI collagen in tissue-engineered cartilage on polymer
      scaffolds.
AB  - Together, the chondrocyte and its pericellular matrix have been collectively
      termed the chondron. Current opinion is that the pericellular matrix has both
      protective and signalling functions between chondrocyte and extracellular matrix.
      Formation of a native chondrocyte pericellular matrix or chondron structure might
      therefore be advantageous when tissue engineering a functional hyaline cartilage
      construct. The presence of chondrons has not been previously described in
      cartilage engineered on a scaffold. In this paper, we describe a modified
      immunochemical method to detect collagen VI, a key molecular marker for the
      pericellular matrix, and an investigation of type VI collagen distribution in
      engineered hyaline cartilage constructs. Cartilage constructs were engineered
      from adult human or bovine hyaline chondrocytes cultured on sponge or nonwoven
      fiber based HYAFF 11 scaffolds. Type VI collagen was detected in all constructs,
      but a distinctive, high-density, chondron-like distribution of collagen VI was
      present only in constructs exhibiting additional features of hyaline cartilage
      engineered using nonwoven HYAFF 11. Chondron structures were localized in areas
      of the extracellular matrix displaying strong collagen II and GAG staining of
      constructs where type II collagen composed a high percentage (over 65%) of the
      total collagen.

PMID- 16579691
TI  - Nonmetabolizable glucose compounds impart cryotolerance to primary rat
      hepatocytes.
AB  - We herein report a novel method for the cryopreservation of hepatocytes using a
      non-metabolizable glucose derivative in an attempt to mimic the natural
      cryoprotective adaptations observed in freeze-tolerant frogs. Primary rat
      hepatocytes were loaded with 3-O-methyl glucose (3OMG) through endogenous glucose
      transporters without evident toxicity. The 3OMG-loaded hepatocytes were then
      frozen in a controlled rate freezer down to -80 degrees C and stored in liquid
      nitrogen at -196 degrees C. Hepatocytes cryopreserved with a relatively small
      amount of intracellular 3OMG (<0.2 M) showed high post-thaw viability and
      maintained long-term hepatospecific functions, including synthesis, metabolism,
      and detoxification. Metabolite uptake and secretion rates were also largely
      preserved in the cryopreserved hepatocytes. This is the first study to
      demonstrate the use of the non-metabolizable glucose derivative 3OMG in
      hepatocyte cryopreservation.

PMID- 16579692
TI  - Use of natural coralline biomaterials as reinforcing and gas-forming agent for
      developing novel hybrid biomatrices: microarchitectural and mechanical studies.
AB  - This paper describes the first attempt in fabrication of three-dimensional
      macroporous composites of chitosan and natural coralline material with pore sizes
      of 300-400 microm, exceeding the upper pore size limit of 250 microm obtained
      with freeze-dried chitosan-based scaffolds. Natural coral particulates of less
      than 20 microm, which is mainly composed of calcium carbonate (CaCO3), was
      simultaneously used as reinforcing phase and gas-forming agent to obtain a
      structure with large pores and improved mechanical and biological properties. The
      reaction between the coralline material and the acidic chitosan polymer solvent,
      which produced carbon dioxide, was rapidly stopped by the subsequent thermally
      induced phase separation technique, leaving coralline particulates in the
      polymeric structure. Scaffolds containing five different proportions of coralline
      material (0, 25, 50, 75, and 100 wt%) were investigated. The coralline-chitosan
      weight ratio was studied for its effects on the physical properties of the
      scaffolds. The relation between scaffold microarchitecture and mechanical
      properties was assessed with scanning electron microscope (SEM), along with micro
      CT imaging and compression testing. The scaffolds were used in bone marrow cell
      culturing experiments to assess the effect of composition on cell behavior
      through cell-material interaction and morphological observation by SEM. Higher
      coralline concentration increased the pore wall thickness and favored large pore
      formation. Varying the coralline particulate to chitosan polymer ratio from 0 to
      75 wt% increased the average pore size from 80 microm to 400 microm while the
      porosity decreased from 91% to 78%. The compressive modulus was improved
      proportionally with the coralline content, and the 75 wt% composites had a
      significantly higher modulus than other chitosan-based scaffold groups. More
      cells were observed on scaffolds with higher coralline content. The cell culture
      experiments indicated that the scaffolds containing coralline material might have
      a high cell affinity, since it allowed fast cell attachment and spreading.

PMID- 16579693
TI  - Fibronectin functional domains coupled to hyaluronan stimulate adult human dermal
      fibroblast responses critical for wound healing.
AB  - Fibronectin (FN) facilitates dermal fibroblast migration during normal wound
      healing. Proteolytic degradation of FN in chronic wounds hampers healing.
      Previously, three FN functional domains (FNfd) have been shown to be sufficient
      for optimal adult human dermal fibroblast migration. Here we report the
      development of an acellular hydrogel matrix comprised of the FNfds coupled to a
      hyaluronan (HA) backbone to stimulate wound repair. Employing Michael-type
      addition, the cysteine- tagged FNfds were first coupled to a homobifunctional PEG
      derivative. Thereafter, these PEG derivative FNfd solutions, containing
      bifunctional PEG-derivative crosslinker were coupled to thiol-modified HA (HA
      DTPH) to obtain a crosslinked hydrogel matrix. When evaluated in vitro, these
      acellular hydrogels were completely cytocompatible. While spreading and
      proliferation of adult human dermal fibroblasts plateaued at higher FNfd bulk
      densities, their rapid and robust migration followed a typical bell-shaped
      response. When implanted in porcine cutaneous wounds, these acellular matrices,
      besides being completely biocompatible, induced rapid and en masse recruitment of
      stromal fibroblasts that was not observed with RGD-tethered or unmodified
      hydrogels. Such constructs might be of great benefit in clinical settings where
      rapid formation of new tissue is needed.

PMID- 16579694
TI  - A new strategy toward improving immunoprotection in cell therapy for diabetes
      mellitus: long-functioning PEGylated islets in vivo.
AB  - Surface modification of islets using poly(ethylene glycol) (PEG) has been studied
      toward preventing immune responses of host for successful islet transplantation.
      In this study, we assessed the functionality of PEGylated islets and immune
      responses of host, as well as the synergistic effects of using PEGylation
      simultaneously with cyclosporine A (CsA) to prevent immune reactions. The average
      period of time for which PEGylated islets functioned normally following islets
      transplantation was 14 days, whereas it was only 5 days for unmodified islets.
      Host's immune cells did not eliminate the PEGylated islets but were observed to
      gather around the islets. On the other hand, unmodified islets were completely
      eliminated. When a low dose of CsA (3 mg/kg/day) was intravenously administered
      at the same time, the PEGylated islets showed stable activity and survived for
      100 days before, that is, the PEGylated islets secreted insulin and were
      preserved from the immune cells. However, unmodified islets survived for 14 days
      on the average, even when CsA was administered. Consequently, it can be suggested
      that the PEGylation of islet surfaces can be an effective approach toward
      reducing the immunogenecity of islets, thus improving the functionality and
      survival time of transplanted islets, especially when CsA was simultaneously
      administered.

PMID- 16579695
TI  - Can mesenchymal stem cells survive under normal impaction force in revision total
      hip replacements?
AB  - Impaction allograft as a scaffold for bone-forming cells is a tissue-engineering
      approach for filling bone defects that are commonly encountered during revision
      total joint replacement (THR). The purpose of this in vitro study is to assess
      the viability of mesenchymal stem cells (MSC) grown on allograft following
      impaction using forces similar to those measured during revision total hip
      replacements. Impaction forces of 0, 3, 6, and 9 kN were used representing normal
      and high impact. The results showed that the viability in the 3 and 6 kN groups
      was not significantly reduced compared with that of the 0 kN group, while the
      survival of the MSCs was significantly reduced after 9 kN impaction force. This
      study suggests that the addition of MSCs to the allograft scaffold will survive
      normal impaction force in revision THR.

PMID- 16579696
TI  - Effect of topical administration of monosodium olpadronate on experimental
      periodontitis in rats.
AB  - BACKGROUND: Periodontitis is characterized by gingival inflammation, periodontal
      pocket formation, and bacterial plaque that lead to alveolar bone destruction.
      Research studies have recently begun to evaluate the effect of antiresorptive
      agents using experimental models of periodontitis. Bisphosphonates are the most
      frequently tested antiresorptive agents; their main effect is inhibition of bone
      resorption. The aim of this study was to perform a histomorphometric evaluation
      of the preventive effect of monosodium olpadronate (OPD), an aminobisphosphonate,
      on experimental periodontitis (EP). METHODS: Twenty male Wistar rats were used in
      this experiment. The animals were assigned to one of two groups: group I: EP; and
      group II: EP plus topical administration of OPD (EP + OPD). The contralateral
      side in both groups served as untreated controls (CI and CII), respectively.
      Mesio-distally oriented sections of each lower first molar were obtained for
      histomorphometric evaluation. RESULTS: The treated group (EP + OPD) exhibited
      marked inhibition of bone loss; interradicular bone volume was significantly
      greater than that observed in the EP group. The height of the periodontal
      ligament in the interradicular alveolar bone, which served as an indirect measure
      of bone loss, was found to be significantly increased in the EP group as compared
      to the EP + OPD group. Osteoclasts in the OPD treated group were detached from
      the bone surface, were round in shape, and exhibited a loss of polarity and lack
      of ruffled borders. CONCLUSIONS: The dose used herein was found to inhibit bone
      loss and to cause marked morphologic changes in osteoclasts. The drug effectively
      prevented bone loss caused by periodontitis.

PMID- 16579697
TI  - Enamel matrix derivative and coronal flaps to cover marginal tissue recessions.
AB  - BACKGROUND: Correcting recession defects is one of the goals of periodontal
      therapy, and the efficacy and predictability of the various techniques are
      important considerations for both patients and clinicians. Several reports have
      examined the outcome of gingival recession treatment by means of coronally
      positioned flaps (CPF) and enamel matrix derivative (EMD). The purpose of this
      study was to clinically evaluate the use of EMD in association with CPF to cover
      localized gingival recessions compared to CPF alone. METHODS: Twenty-two patients
      with Miller Class I or II gingival recessions >2 mm were included. One recession
      from each patient was treated in the study. Two treatments were randomly
      assigned: coronally positioned flap with EMD (test) and coronally positioned flap
      alone (control). Clinical parameters measured at baseline and 1, 6, and 12 months
      included gingival index, plaque index, probing depth, clinical attachment level,
      vertical and horizontal recession, and width of keratinized gingiva. RESULTS: At
      12 months, both treatment modalities showed significant root coverage, gain in
      clinical attachment, and gain in width of keratinized gingiva (P <0.05). Vertical
      recessions were reduced from 2.68 +/- 1.63 mm to 0.36 +/- 0.60 mm in the test
      group and from 2.31 +/- 1.52 mm to 0.90 +/- 0.95 mm in the control group.
      Horizontal recessions decreased from 4.27 +/- 2.06 mm to 0.77 +/- 0.87 mm in the
      test group and from 3.68 +/- 1.91 mm to 1.72 +/- 1.31 mm in the control group.
      Changes in keratinized gingiva went from 3.81 +/- 1.95 mm to 4.63 +/- 2.15 mm in
      the test group and from 3.31 +/- 1.81 mm to 3.27 +/- 1.80 mm in the control
      group. When both treatments were compared at 12 months, there was a significant
      difference in vertical tooth coverage and gain in keratinized gingiva in favor of
      the experimental group (P <0.05). The average percentage of root coverage for
      test and control groups was 88.6% and 62.2%, respectively. CONCLUSIONS: The
      coronally positioned flap alone or with EMD is an effective procedure to cover
      localized gingival recessions. The addition of EMD significantly improves the
      amount of root coverage.

PMID- 16579698
TI  - Relationship of serum advanced glycation end products with deterioration of
      periodontitis in type 2 diabetes patients.
AB  - BACKGROUND: A close relationship between diabetes and chronic periodontitis has
      been demonstrated. We previously found that Porphyromonas gingivalis with the
      type II fimA gene is an infectious factor closely associated with the
      deterioration seen in diabetic periodontitis patients. In the present study, we
      examined whether other biomarkers are related to the development and
      deterioration of periodontitis often seen in type 2 diabetic individuals.
      METHODS: A total of 97 type 2 diabetes patients with and without periodontitis
      were recruited, and their periodontal and diabetic conditions were analyzed. The
      ratio (%) of teeth with an attachment loss >5 mm among all teeth in each subject
      was used as an index of periodontal deterioration. Peripheral blood was tested
      for levels of glycated hemoglobin (HbA1c), advanced glycation end products
      (AGEs), C-reactive protein (CRP), and cytokines (tumor necrosis factor [TNF]
      alpha and interleukin [IL]-1beta). Subgingival plaque samples were also examined
      for the occurrences of Actinobacillus actinomycetemcomitans, Tannerella
      forsythensis, Treponema denticola, and Prevotella intermedia. RESULTS: Serum AGEs
      were significantly associated with deterioration of periodontitis, whereas no
      other serum biochemical marker or bacterial occurrence showed a clear
      relationship with that condition. CONCLUSION: AGEs may be factors associated with
      diabetic periodontitis and may be useful as biomarkers that reflect such
      deterioration.

PMID- 16579699
TI  - Parathyroid hormone induces mitogen-activated kinase phosphatase 1 in murine
      osteoblasts primarily through cAMP-protein kinase A signaling.
AB  - BACKGROUND: Parathyroid hormone (PTH) regulates osteoblast function by binding to
      the PTH receptor 1 (PTHR1) to activate downstream signaling to induce expression
      of primary response genes (PRGs), which affect various aspects of the osteoblast
      phenotype. We previously identified PTH-induced PRGs in MC3T3-E1 cells, including
      mitogen-activated protein kinase (MAPK) phosphatase 1 (mkp1), which
      dephosphorylates members of the MAPK family. The aim of this study was to explore
      the molecular mechanisms of PTH's induction of mkp1 in primary mouse osteoblasts.
      METHODS: Northern and Western analyses were used to determine mkp1 mRNA and
      protein expression. In vivo experiments were also performed to determine PTH's
      effect on mkp1 in mouse calvariae and long bones. RESULTS: A total of 10 nM PTH
      and PTH-related protein (PTHrP) maximally induced mkp1 mRNA levels after 1 hour
      in osteoblasts. PTH also increased mkp1 protein expression, and induced mkp1 mRNA
      independent of new protein synthesis. PTHR1 triggers protein kinase A (PKA), PKC,
      and calcium pathways. Although PKA and PKC agonists induced mkp1 mRNA levels,
      only cyclic adenosine 3':5'-monophosphate (cAMP)-PKA inhibition blocked PTH
      induced mkp1 mRNA levels. These data suggest that PTH-induced mkp1 mRNA levels
      are primarily mediated through the cAMP-PKA pathway. Further, prostaglandin E2
      (PGE2), which activates cAMP-PKA and PKC, induced mkp1 mRNA to a greater extent
      than PGF2alpha and fluprostenol, which activate PKC signaling only. Finally, PTH
      maximally induced mkp1 mRNA levels in mouse calvariae and long bones in vivo at
      0.5 hours. CONCLUSIONS: mkp1's in vitro and in vivo induction in PTH-target
      tissues suggests its involvement in some of the effects of PTH on osteoblast
      function. mkp1 may be an important target gene in the anabolic effect of PTH on
      osteoblasts.

PMID- 16579700
TI  - Local oxygen therapy for treating acute necrotizing periodontal disease in
      smokers.
AB  - BACKGROUND: The main aim of treatment for acute necrotizing periodontal disease
      is fast and effective reduction of anaerobic destructive microorganisms to avoid
      periodontal damage. The effect of adjunctive local oxygen therapy in the
      treatment of necrotizing periodontal disease was examined in this study. METHODS:
      Thirty patients with acute necrotizing periodontal disease were treated with the
      systemic antibiotics amoxicillin, clavulanic acid, and metronidazole. In 15 out
      of 30 patients, adjunctive local oxygen therapy was administered. The patients
      were followed from the first to 10th day of treatment with clinical and
      bacteriological examinations. The clinical examination registered gingival
      bleeding, periodontal probing depth, and attachment loss; to follow up
      microbiological colonization of the periodontal sulcus, five representative
      bacteria were registered by a semiquantitative DNA polymerase chain reaction
      test. RESULTS: In both groups of patients, colonization with Prevotella
      intermedia, Tannerella forsythensis, and Treponema denticola was initially
      positive. None of these three microorganisms were completely eradicated in any of
      the patients in the group without oxygen therapy within the first 10 days of
      treatment. In the group with adjunctive oxygen therapy, all patients either
      showed a reduction in or complete eradication of the microorganisms, resulting in
      more rapid clinical restitution with less periodontal destruction. CONCLUSIONS:
      Adjunctive oxygen therapy results in early eradication of pathogenic anaerobic
      microorganisms in cases of acute necrotizing periodontal disease. The damage to
      periodontal tissue is reduced.

PMID- 16579701
TI  - Effect of a hydroxyapatite tricalcium phosphate alloplast on osseous repair in
      the rat calvarium.
AB  - BACKGROUND: Bony defects caused by periodontitis are often treated by
      regenerative therapy using autografts and/or allografts. Alloplasts, such as
      hydroxyapatite or ceramics, are also used as osteoconductive materials that serve
      as a scaffold for new bony ingrowth. The purpose of this study was to determine
      the effect of hydroxyapatite tricalcium phosphate (HA-TCP) on osseous repair in
      the rat calvarium. METHODS: Forty-four adult male Harlan Sprague-Dawley rats were
      assigned to one of four treatment groups: HA-TCP macroporous disk, HA-TCP
      microporous disk, HA-TCP granules, and demineralized freeze-dried bone (DFDB).
      The materials were placed into 8-mm calvarial critical-size defects (CSD).
      Calvariae were harvested at 10 weeks post-surgery and evaluated
      histomorphometrically. RESULTS: The DFDB group had significantly (P <0.05) more
      new bone formation (47%) than any other group. The HA-TCP macroporous disk group
      had significantly (P <0.05) more new bone formation (19.7%) than the HA-TCP
      microporous disk (8.5%) or HA-TCP granule (6.9%) groups. CONCLUSIONS: The HA-TCP
      macroporous disk may elicit significant new bone formation due to its rigid space
      maintaining scaffold and pore size for vascular ingrowth. It is well tolerated by
      host tissues and may be a suitable carrier for growth factors.

PMID- 16579702
TI  - Effect of early membrane removal on regeneration of Class II furcation defects in
      dogs.
AB  - BACKGROUND: This study evaluated the influence of early removal of an expanded
      polytetrafluoroethylene (ePTFE) membrane on periodontal regeneration. METHODS:
      The third and fourth mandibular bicuspids of six healthy mongrel dogs were used.
      Class II furcation lesions were surgically created making lesions chronic for 21
      days. Full flaps were elevated, and ePTFE membranes were adapted over the
      defects. The membranes were removed at 2 weeks on the experimental sides (test
      group [TGr]) and at 4 weeks on the control side (control group [CGr]). The dogs
      were sacrificed 12 weeks following placement of the membranes, and the teeth were
      histologically processed. Area measurements of new tissue (NT), epithelium (EP),
      connective tissue (CT), and new bone (NB) and linear measurements of bone height
      (BH) and new cementum (NC) were made. Wilcoxon signed rank test (P <0.05; N = 6)
      was carried out to determine differences between groups. RESULTS: The area
      measurements (in mm2) for TGr and CGr, respectively, were as follows: 14.32 +/-
      4.01 and 12.46 +/- 3.54 (NT); 0.04 +/- 0.09 and 0.01 +/- 0.04 (EP); 2.31 +/- 2.60
      and 1.91 +/- 2.96 (CT); and 9.56 +/- 3.77 and 8.79 +/- 2.99 (NB). The results of
      the linear measurements (in mm) for TGr and CGr, respectively, were as follows:
      3.85 +/- 1.21 and 4.03 +/- 0.94 (BH) and 10.91 +/- 1.72 and 10.59 +/- 1.80 (NC).
      There were no statistically significant differences between TGr and CGr for any
      measurement. CONCLUSION: The early removal of ePTFE membranes in Class II
      furcation defects in dogs did not affect periodontal regeneration.

PMID- 16579703
TI  - Increased expression of vascular endothelial growth factor in cyclosporin A
      induced gingival overgrowth in rats.
AB  - BACKGROUND: Gingival overgrowth is a side effect associated with cyclosporin A
      (CsA) therapy. The lesion is characterized by increased epithelial thickness,
      enlargement of connective tissue, and increased vascularization. The aim of this
      experimental study was to examine the role of vascular endothelial growth factor
      (VEGF) in the pathogenesis of CsA-induced gingival overgrowth. METHODS: Twenty
      male Wistar rats were divided into two groups of 10 animals each. For the
      development of gingival overgrowth, one group received CsA therapy subcutaneously
      in a daily dose of 10 mg/kg for 60 days, and the other group was used as a
      control. At the end of the experimental period, rats were subsequently
      decapitated, and the mandibles with the surrounding gingiva and soft tissue were
      removed. Half of each sample was used for histomorphometric analysis, and the
      other half was used for biochemical analysis. Histomorphometric analysis included
      the measurements of the number and diameter of blood vessel profiles under a
      microscope, and biochemical analysis included the assessment of VEGF
      concentration by enzyme-linked immunosorbent assay (ELISA). RESULTS: The
      histomorphometric findings showed that the number of blood vessel profiles
      increased in the CsA group compared to the control group (P <0.001), although the
      increase in the diameter of blood vessel profiles was not significant (P >0.05).
      The biochemical findings showed that in vivo VEGF expression was higher in the
      CsA group compared to the control group (P <0.001). CONCLUSION: The results of
      this study suggest that increased VEGF expression may be associated with the
      pathogenesis of CsA-induced gingival overgrowth.

PMID- 16579704
TI  - Increase in probing depth is correlated with a higher number of Prevotella
      intermedia genotypes.
AB  - BACKGROUND: The aims of this study were to determine the genotypic diversity of
      Prevotella intermedia in subgingival plaque samples by using two techniques,
      arbitrarily primed polymerase chain reaction (AP-PCR) and heteroduplex analysis,
      and to assess the relationship of this diversity with increase in probing depth.
      METHODS: The subgingival plaque samples were obtained from 12 patients using
      paper points inserted into periodontal pockets (diseased sites) and healthy
      gingival sulci (healthy sites) of the same subjects. After isolation and
      identification, AP-PCR was performed for genotypic characterization of P.
      intermedia (80 isolates). The clinical samples with a positive result for P.
      intermedia were amplified by 16S rRNA-based PCR method, and the amplicons were
      subjected to heteroduplex analysis. RESULTS: The agreement between the two
      methods was very high; the AP-PCR and heteroduplex analysis showed that subjects
      harbored between one and five distinct genotypes of P. intermedia, with a
      positive association between numbers of genotypes by AP-PCR (P = 0.0042) or
      heteroduplex (P = 0.0099) and increase in probing depth. No matching of P.
      intermedia genotypes was observed between healthy and diseased sites of the same
      individual. Interindividual analyses demonstrated absence of identical clones and
      indicated a high level of genetic diversity in the species. CONCLUSION: A clear
      relationship was observed between a higher number of genotypes and increase in
      probing depth; these results suggest that environmental challenges in the
      periodontal pockets may modulate the microbiota by selecting genotypes best able
      to exploit the environment.

PMID- 16579705
TI  - Gingival crevicular fluid alkaline phosphatase levels in postmenopausal women:
      effects of phase I periodontal treatment.
AB  - BACKGROUND: The aim of this study was to determine how estrogen status may
      possibly influence gingival crevicular fluid (GCF) alkaline phosphatase (ALP)
      levels in estrogen-deficient (ED) and -sufficient (ES) postmenopausal women at
      baseline (BL) and 1 year after periodontal phase I treatment (AT). METHODS:
      Thirty-six postmenopausal women on estrogen supplements (mean serum estradiol
      levels >30 pg/ml; estrogen sufficient) and 37 postmenopausal women not on
      estrogen supplements (mean serum estradiol levels <30 pg/ml; ED) were divided
      into two subgroups as chronic periodontitis and clinically healthy controls after
      clinical and radiographic examination. The ES group consisted of 19 control
      (ES/C) and 17 chronic periodontitis (ES/P) patients, and the ED group consisted
      of 20 control (ED/C) and 17 chronic periodontitis (ED/P) patients. Plaque (PI)
      and gingival (GI) indices, bleeding on probing (BOP), probing depths (PD),
      clinical attachment loss (CAL) scores, and GCF samples were recorded at BL and
      AT. The levels of ALP in the GCF were measured photometrically. The paired
      samples Student t and Wilcoxon tests were used to compare the ALP levels and
      clinical parameters between BL and AT. The correlation among the ALP and clinical
      parameters was analyzed using the Pearson correlation. RESULTS: The mean of all
      clinical parameters (PI, GI, BOP, PD, and CAL) was significantly (P <0.05) higher
      in periodontitis groups (ES/P and ED/P) than controls (ES/C and ED/C).
      Periodontitis groups (ES/P and ED/P) demonstrated significantly increased GCF
      volumes and GCF ALP levels (P <0.05) compared to controls (ES/C and ED/C). There
      were no significant differences in the concentrations of ALP between
      periodontitis and control groups (P >0.05). The BL GCF ALP total levels of the
      ED/P group were significantly higher than the ES/P group (P <0.05). The BL and AT
      serum ALP levels of the ED/P group were not significantly but were numerically
      higher than the ES/P group. One year after periodontal treatment, the GCF volume,
      GCF ALP total, and concentrations decreased significantly in both periodontitis
      groups (P <0.05). However, the GCF ALP levels were still numerically higher in
      the ED/P group. A positive statistical correlation was found between total ALP
      levels and PD (r = 0.621; P <0.05). CONCLUSION: These data suggest that the
      presence of ALP in GCF is not simply a reflection of the local inflammation state
      and that a patient's estrogen status may possibly influence local ALP levels in
      GCF.

PMID- 16579706
TI  - Inflammatory infiltrate, microvessel density, nitric oxide synthase expression,
      vascular endothelial growth factor expression, and proliferative activity in peri
      implant soft tissues around titanium and zirconium oxide healing caps.
AB  - BACKGROUND: The aim of the present study in humans was to conduct a comparative
      immunohistochemical evaluation of vascular endothelial growth factor (VEGF) and
      nitric oxide synthase (NOS) expression, inflammatory infiltrate, proliferative
      activity expression, and microvessel density (MVD) in peri-implant soft tissues
      of titanium and zirconium oxide healing caps. METHODS: Five patients, three men
      and two women (aged 30 to 66 years; mean: 49 years), participated in this study.
      All patients received dental implants that were 3.8 mm in diameter and 11 mm in
      length. All implants were left to heal in a non-submerged (single-stage) mode.
      Healing caps (3.8 mm in diameter and 3.0 mm in height) were inserted in all
      implants. Half of the implants were supplied with standard, prefabricated caps of
      commercially pure titanium, whereas the other half were provided with test
      zirconium oxide caps. After a 6-month healing period, a gingival biopsy was
      performed with a circular scalpel (5.5 mm in diameter) around the healing caps of
      both groups, without unscrewing or removing the healing caps. The dimensions of
      the gingival biopsies were 1.7 mm (5.5-3.8 mm) in thickness and 3 mm in height.
      RESULTS: Statistically significant differences were found in the microvessel
      density between titanium and zirconium oxide healing caps and group II (P < or =
      0.0001). Statistically significant differences were likewise found in the low and
      high intensities of NOS1, NOS3, and VEGF (P < or = 0.0001). In conclusion, the
      high intensity of NOS1, NOS3, and VEGF were mostly expressed in the titanium
      group, whereas the low intensity of NOS1, NOS3, and VEGF were mostly expressed in
      the zirconium oxide group. CONCLUSIONS: In our specimens, the inflammatory
      infiltrate was mostly present in the titanium specimens. Their extension was much
      larger than that of the zirconium oxide specimens. Higher values of MVD were
      observed in the titanium specimens (29.1 versus 15.8). In addition, a higher
      expression of VEGF intensity was observed in the peri-implant tissues of titanium
      healing caps, whereas predominantly lower expressions of VEGF intensity were
      noted around the zirconium oxide healing caps. The Ki-67 expression was higher in
      the titanium specimens. All these data revealed that the tissues around titanium
      healing caps underwent a higher rate of inflammation-associated processes, most
      probably correlated to the higher inflammation processes observed in these
      tissues. A higher intensity expression of NOS1 and NOS3 was recorded in the
      tissues around titanium, whereas, on the contrary, a lower intensity of
      expression was found in the tissues around zirconium oxide specimens. These
      latter data indicate that the higher expression of these two mediators could be
      correlated to the higher amount of bacteria present around the titanium samples.

PMID- 16579707
TI  - Coronally positioned flap for root coverage: poorer outcomes in smokers.
AB  - BACKGROUND: Gingival recession is significantly more common among smokers, while
      the relative outcome of various root coverage procedures in smokers, compared to
      non-smokers, is debatable. The objective of this study was to evaluate the
      influence of cigarette smoking on the outcome of coronally positioned flap (CPF)
      in the treatment of Miller Class I gingival recession defects. METHODS: Ten
      current smokers (> or = 10 cigarettes daily for at least 5 years) and 10 non
      smokers (never smokers), each with one 2- to 3-mm Miller Class I recession defect
      in an upper canine or bicuspid, were treated with CPF. At baseline and 6 months,
      clinical parameters, probing depth (PD), clinical attachment level (CAL),
      recession depth (RD), and apico-coronal width of keratinized tissue (KT) were
      determined. RESULTS: Intragroup analysis showed that CPF was able to reduce RD
      and improve CAL in both groups (P <0.05). Intergroup analysis demonstrated that
      smokers presented greater residual RD at 6 months and lower percentage of root
      coverage (69.3% versus 91.3%; P <0.05). No smokers obtained complete root
      coverage compared to 50% of non-smokers (P <0.05). CONCLUSIONS: Within the limits
      of the present study, it can be concluded that CPF provides benefits for both
      smokers and non-smokers in terms of root coverage of shallow Miller Class I
      recession defects. However, cigarette smoking negatively impacts the clinical
      outcomes, specifically residual recession, percent root coverage, and frequency
      of complete root coverage.

PMID- 16579708
TI  - Long-term results of guided tissue regeneration therapy with non-resorbable and
      bioabsorbable barriers. III. Class II furcations after 10 years.
AB  - BACKGROUND: The aim of this 10-year follow-up was to evaluate the long-term
      results after guided tissue regeneration (GTR) therapy of Class II furcation
      defects using non-resorbable and bioabsorbable barriers clinically. METHODS: In
      nine patients with advanced periodontitis, nine pairs of contralateral Class II
      furcation defects were treated. Within each patient, one defect received a non
      resorbable expanded polytetrafluoroethylene barrier (ePTFE; C) and the other a
      bioabsorbable (polyglactin 910; T) barrier by random assignment. At baseline and
      12 and 120 +/- 6 months after surgery, clinical parameters were obtained.
      RESULTS: Twelve and 120 months after GTR therapy, statistically significant (P
      <0.05) horizontal clinical attachment level (CAL-H) gain was observed in both
      groups (C12: 1.9 +/- 0.5 mm; C120: 1.1 +/- 1.3 mm; T12: 1.9 +/- 0.8 mm; T120: 1.7
      +/- 1.4 mm). However, one patient with furcations that had been assessed as Class
      I 12 months after GTR therapy had lost two teeth after 10 years, and another
      patient had lost more than 2 mm CAL-H at one furcation from 12 to 120 +/- 6
      months post-surgery 10 years after implantation of an ePTFE barrier. Horizontal
      bone sounding revealed similar bone gain in both groups 120 +/- 6 months post
      surgery (C120: 0.8 +/- 1.0 mm; T120: 1.1 +/- 1.1 mm). CONCLUSIONS: CAL-H gain
      achieved after GTR therapy in Class II furcations was stable after 10 years in 15
      of 18 defects (83%). The study failed to show a statistically significant
      difference in stability of CAL-H gain between group C and T 10 years after GTR
      therapy.

PMID- 16579709
TI  - Angiographically confirmed coronary heart disease and periodontal disease in
      middle-aged males.
AB  - BACKGROUND: The aim of this study was to investigate whether an association could
      be demonstrated between coronary heart disease (CHD) and chronic periodontitis in
      a population of middle-aged males in Northern Ireland. METHODS: A case-control
      design was used. Cases were men aged over 40 years with angiographically proven
      CHD. Controls were age-matched males, with no evidence of CHD, randomly drawn
      from the same locality as the cases. Each subject had a clinical periodontal
      examination and completed a detailed sociodemographic questionnaire. High
      sensitivity C-reactive protein (CRP) was measured in serum by immunoturbidimetry.
      RESULTS: There were 92 cases (mean age 56.7 years; SD = 6.3) and 79 controls
      (mean age 58.2 years; SD = 6.7). The CHD cases had an average of three teeth less
      than the controls (P <0.0001). A higher proportion of sites examined in cases
      than controls had plaque (P = 0.004), bleeding on probing (P = 0.013), and
      probing depths of > or = 4 mm (P = 0.006) or > or = 6 mm (P = 0.03). Subjects
      with > or = 4 mm pocketing in more than 20% of their interproximal sites and
      those with deep pocketing (> or = 6 mm) were classified as having poor
      periodontal status. A total of 35 cases (38%), compared to only 13 controls
      (16%), had a poor periodontal status (P = 0.0017). Men with a poor periodontal
      condition had higher levels of CRP (median 2.19 mg/l) than those with good
      periodontal health (median 1.42 mg/l), P = 0.007. After adjusting for smoking,
      academic achievement, alcohol consumption, unemployment, ability to maintain body
      weight, regular exercise, ability to relax daily, having a hobby or pastime,
      plaque, and CRP, logistic regression analysis showed that poor periodontal status
      was significantly associated with CHD, with an adjusted odds ratio of 3.06 and
      95% confidence intervals of 1.02 to 9.17, P = 0.046. CONCLUSIONS: There was an
      association between coronary heart disease and poor periodontal status in the
      middle-aged males investigated. This association was independent of diabetes and
      all other cardiovascular risk factors investigated.

PMID- 16579710
TI  - EDTA gel root conditioning: lack of effect on clinical and radiographic outcomes
      of intrabony defect treatment with enamel matrix derivative.
AB  - BACKGROUND: The adjunctive use of enamel matrix derivative (EMD) in the surgical
      therapy of intrabony defects results in improved outcomes compared to surgical
      debridement alone. However, the role of EDTA root conditioning in EMD therapy has
      not been investigated. The purpose of this study was to compare the 12-month
      outcomes of EMD application with and without EDTA root conditioning in intrabony
      defect surgical therapy. METHODS: Twenty-eight chronic periodontitis patients,
      each contributing a 2- or 3-wall intrabony defect (> or = 4 mm deep and > or = 2
      mm wide), participated. Patients consecutively received surgical treatment with
      either EMD alone (first 13 patients) or EMD + EDTA (subsequent 15 patients).
      Probing depth (PD), clinical attachment level (CAL), and gingival margin
      position, i.e., recession (REC) were the clinical parameters recorded. Recorded
      radiographic parameters were the distances from 1) cemento-enamel junction to
      bone crest (CEJ to BC), 2) CEJ to base of the defect (CEJ to BD), and 3) BC to
      BD. RESULTS: Intragroup analysis showed that both EMD alone and EMD + EDTA led to
      significant PD reduction, CAL gain, and REC increase 1 year postoperatively. Both
      groups had >60% mean radiographic defect resolution (change in BC to BD). None of
      the recorded parameters were significantly different between the two groups,
      either at baseline or postoperatively. CONCLUSIONS: These results suggest that
      clinical and radiographic outcomes of intrabony defect EMD therapy do not depend
      on the use of EDTA gel root conditioning. The potential contribution of EDTA gel
      root conditioning to the histological outcomes reported with EMD therapy remains
      to be determined.

PMID- 16579711
TI  - Short-term clinical and microbiologic effects of pocket debridement with an
      Er:YAG laser during periodontal maintenance.
AB  - BACKGROUND: The erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser is
      considered a useful tool for subgingival debridement because the laser treatment
      creates minimal damage to the root surface and has potential antimicrobial
      effects. The aim of this randomized controlled clinical trial was to evaluate
      clinical and microbiologic effects of pocket debridement using an Er:YAG laser in
      patients during periodontal maintenance. METHODS: Twenty patients at a recall
      visit for maintenance were consecutively recruited if presenting at least four
      teeth with residual probing depth (PD) > or = 5 mm. Two pockets in each of two
      jaw quadrants were randomly assigned to subgingival debridement using 1) an
      Er:YAG laser (test) or 2) an ultrasonic scaler (control). The laser beam was set
      at 160 mJ with a pulse frequency of 10 Hz. Clinical variables were recorded at
      baseline, 1 month, and 4 months after treatment. Primary clinical outcome
      variables were changes in PD and clinical attachment level (CAL). Microbiologic
      analysis of subgingival samples was performed at baseline, 2 days, and 30 days
      after treatment using a checkerboard DNA-DNA hybridization technique against 12
      periodontal disease-associated species. RESULTS: The mean initial PD was 6.0 mm
      (SD: 1.2) in the test group and 5.8 mm (SD: 0.9) in the control group. At 1 month
      post-treatment, the PD reduction was significantly greater for test than control
      sites (0.9 versus 0.5 mm; P <0.05). The CAL gain also was significantly greater
      (0.5 versus 0.06 mm; P <0.01). At the 4-month examination, no significant
      differences were detected in PD reduction (1.1 versus 1.0 mm) or CAL gain (0.6
      versus 0.4 mm). Both treatments resulted in reduction of the subgingival
      microflora. No significant differences in microbiologic composition were
      identified between the treatment groups at various time intervals. Degree of
      treatment discomfort scored significantly lower for the test than the control
      treatment modality. CONCLUSION: The results of the trial failed to demonstrate
      any apparent advantage of using an Er:YAG laser for subgingival debridement,
      except less treatment discomfort perceived by the patients.

PMID- 16579713
TI  - Ligneous periodontitis and Ehlers-Danlos syndrome.
AB  - BACKGROUND: Generalized membranous gingival enlargement due to an accumulation of
      fibrin deposits associated with severe alveolar bone loss (ligneous
      periodontitis) is a rare condition, and plasminogen deficiency seems to play a
      central role in its pathogenesis. However, this condition has not been described
      in association with syndromes. This article reports a case of ligneous
      periodontitis in a boy with the classic type of Ehlers-Danlos syndrome (EDS).
      METHODS: A 12-year-old white male presented with generalized gingival overgrowth
      and severe alveolar bone loss. A physical examination revealed clinical signs of
      EDS (velvety skin with mild hyperextensibility, marked hypermobility of the limb
      joints, atrophic scars on his knees, and easy bruising), which is associated with
      a positive family history for joint hypermobility. A biopsy of gingival tissues
      was submitted for routine histology, hematoxylin and eosin (H&E), and direct
      immunofluorescence (antifibrinogen). An evaluation of plasminogen activity was
      also performed. RESULTS: Histopathology revealed chronic periodontitis with
      fibrinoid material deposition, and direct immunofluorescence proved to be
      positive for fibrin. Functional plasminogen was reduced. A conclusive diagnosis
      of ligneous periodontitis due to plasminogen deficiency associated with the
      classic type of EDS was rendered. CONCLUSIONS: Ehlers-Danlos syndrome can be
      associated with ligneous periodontitis. In the present case, the histologic
      examination represented an important tool in the differential diagnosis, because
      it ruled out EDS type VIII as the associated systemic factor to periodontal
      breakdown.

PMID- 16579712
TI  - Myeloid sarcoma occurring concurrently with drug-induced gingival enlargement.
AB  - BACKGROUND: Myeloid sarcoma is an extramedullary malignancy of myeloblasts. An
      unusual case of myeloid sarcoma presenting in the gingiva and affected by drug
      induced gingival enlargement is presented. METHODS: A 63-year-old male taking
      amlodipine for his hypertension presented with a 3-week gingival enlargement.
      Although the obvious clinical impression was that of drug-induced gingival
      enlargement, an incisional biopsy was performed to corroborate chemical
      enlargement while ruling out diseases such as lymphoma and leukemia. RESULTS:
      Microscopic examination of the thickened gingiva revealed surface stratified
      squamous epithelium having needle-like rete pegs characteristic of drug-induced
      gingival enlargement. Beneath the surface epithelium, the fibrous tissue was
      virtually replaced by a dense infiltrate of malignant cells. Immunohistochemical
      studies were performed with CD117 and myeloperoxidase identifying the malignant
      cell population as myeloblasts, leading to a diagnosis of myeloid sarcoma.
      CONCLUSION: Myeloid sarcoma and hematopoietic malignancies must be included in a
      differential diagnosis of gingival enlargement until the definitive diagnosis is
      reached by histologic/laboratory examination.

PMID- 16579714
TI  - Maxillary sinusitis and periapical abscess following periodontal therapy: a case
      report using three-dimensional evaluation.
AB  - BACKGROUND: Maxillary sinusitis may develop from the extension of periodontal
      disease. In this case, reconstructed three-dimensional images from multidetector
      spiral computed tomographs were helpful in evaluating periodontal bony defects
      and their relationship with the maxillary sinus. METHODS: A 42-year-old woman in
      good general health presented with a chronic deep periodontal pocket on the
      palatal and interproximal aspects of tooth #14. Probing depths of the tooth
      ranged from 2 to 9 mm, and it exhibited a Class 1 mobility. Radiographs revealed
      a close relationship between the root apex and the maxillary sinus. The patient's
      periodontal diagnosis was localized severe chronic periodontitis. Treatment of
      the tooth consisted of cause-related therapy, surgical exploration, and bone
      grafting. A very deep circumferential bony defect at the palatal root of tooth
      #14 was noted during surgery. After the operation, the wound healed without
      incidence, but 10 days later, a maxillary sinusitis and periapical abscess
      developed. To control the infection, an evaluation of sinus and alveolus using
      computed tomographs was performed, systemic antibiotics were prescribed, and
      endodontic treatment was initiated. RESULTS: Two weeks after surgical treatment,
      the infection was relieved with the help of antibiotics and endodontic treatment.
      Bilateral bony communications between the maxillary sinus and periodontal bony
      defect of maxillary first molars were shown on three-dimensional computed
      tomographs. The digitally reconstructed images added valuable information for
      evaluating the periodontal defects. CONCLUSION: Three-dimensional images from
      spiral computed tomographs (CT) aided in evaluating and treating the close
      relationship between maxillary sinus disease and adjacent periodontal defects.

PMID- 16579715
TI  - Management of interdental papillae loss with forced eruption, immediate
      implantation, and root-form pontic.
AB  - BACKGROUND: A 25-year-old Asian woman complained of an unesthetic black triangle
      between her upper right front teeth. Defective interdental papillae may result
      from external root resorption, which makes esthetic restoration more difficult. A
      combined use of forced eruption, immediate implant placement, and a root-form
      pontic made a successful esthetic and functional restoration. METHODS: The
      treatment sequences of this patient included short-term forced eruption,
      subsequent immediate implant placement after tooth extraction, and a provisional
      root-form pontic restoration. A final prosthesis was completed 6 months later,
      followed by clinical maintenance. RESULTS: Papillae were augmented by forced
      eruption. After immediate implantation and root-form pontic placement had been
      performed, the peri-implant soft and hard tissues were manipulated and maintained
      in a stable state. CONCLUSIONS: We successfully reconstructed the interdental
      papillae and replaced the deficient tooth with an immediate implantation. During
      2 years of follow-up, the implant and peri-implant structures remained stable and
      healthy.

PMID- 16579717
TI  - Impact of cognitive behavior therapy on health-related quality of life among
      adult hypnotic users with chronic insomnia.
AB  - Results were combined from representative surveys of health related quality of
      life (HRQoL; n=11,877; age range=16-104) with data from a randomized controlled
      trial of cognitive behavior therapy for chronic insomnia (n=209; age range=31
      92). Secondary analyses of scores from the SF-36 measure of HRQoL were conducted
      in order: (a) to compare the health related quality of life profiles of adult
      hypnotic users with chronic insomnia with those of population norms, and (b) to
      assess the impact of cognitive behavior therapy (CBT) for insomnia on HRQoL
      outcomes over 6 months. Compared with the primary care reference values, HRQoL
      among the trial participants at baseline was generally poorer. The magnitude of
      these decrements reduced markedly with advancing age. In the evaluation of the
      CBT intervention, statistically significant differences in SF-36 scores in favor
      of the intervention were present for physical functioning, emotional role
      limitation, and mental health over 6 months. Overall, this study shows that the
      SF-36 can play an important role in describing HRQoL in this patient group, and
      in the evaluation of interventions within this group.

PMID- 16579716
TI  - Unilateral severe chronic periodontitis associated with ipsilateral surgical
      resection of cranial nerves V, VI, and VII.
AB  - BACKGROUND: The central and peripheral nervous systems participate in several
      local physiological and pathological processes. There is experimental evidence
      that the inflammatory, local immune, and wound healing responses of a tissue can
      be modulated by its innervation. The aim of this clinical report is to present a
      case of unilateral severe periodontitis associated with ipsilateral surgical
      resection of the fifth, sixth, and seventh cranial nerves and to discuss the
      possible contribution of the nervous system to periodontal pathogenesis. METHODS:
      A 39-year-old female patient with a history of a cerebrovascular accident caused
      by a right pontine arteriovenous malformation and destruction of the right fifth,
      sixth, and seventh cranial nerves was diagnosed with severe chronic periodontitis
      affecting only the right maxillary and mandibular quadrants. The patient's oral
      hygiene was similar for right and left sides of the mouth. Percentages of tooth
      surfaces carrying dental plaque were 41% and 36% for right and left sides,
      respectively. Non-surgical and surgical periodontal therapy was performed, and
      the patient was placed on a regular periodontal maintenance schedule. RESULTS:
      Healing following initial periodontal therapy and osseous periodontal surgery
      occurred without complications. Follow-up clinical findings at 1 year revealed
      stable periodontal health. CONCLUSIONS: This case report suggests that
      periodontal innervation may contribute to the regulation of local processes
      involved in periodontitis pathogenesis. It also suggests that periodontal therapy
      can be performed successfully at sites and in patients affected by paralysis.

PMID- 16579718
TI  - Daytime functioning in primary insomnia: does attentional focus contribute to
      real or perceived impairment?
AB  - A study was conducted to test the proposal that self-focused attention or
      monitoring exacerbates the perception of poor daytime functioning in the absence
      of objective deficits among individuals with insomnia. Fifty-one participants
      meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria
      for primary insomnia were randomly assigned to a self-focus group (viewing
      themselves on a TV monitor), a monitoring group (instructed to focus on their
      thoughts, body sensations, mood, and performance), or a no instruction group
      while completing a battery of neuropsychological tests. The results indicated
      that all participants performed within published normative ranges on all tests.
      The groups did not differ on their objective test performance, but the self-focus
      group perceived their performance on the tests as significantly worse than the no
      instruction group. These findings suggest that self-focused attention may
      contribute to perceived impairment in daytime functioning in primary insomnia.

PMID- 16579719
TI  - Insomnia as a risk factor for onset of depression in the elderly.
AB  - There are at least 9 studies that provide evidence that insomnia is a significant
      risk factor for recurrent and new onset major depressive disorder (MDD), two of
      which suggest that this association also exists specifically for the elderly. In
      this study, archival data from a community sample of healthy elderly participants
      were used to assess the extent to which insomnia predicts future illness in this
      age cohort. Out of the 147 participants with no prior history of mental illness,
      66 participants were classified as having no insomnia, 47 had indeterminate
      insomnia, and 34 had persistent insomnia. Twelve participants developed MDD
      during the 1-year follow-up period. Two had no insomnia, 4 had indeterminate
      insomnia, and 6 had persistent insomnia. Persistent insomnia with onset of
      depression occurred only in female participants and was significantly associated
      with middle insomnia. These data suggest that elderly participants with
      persistent insomnia are at greater risk for the development of new onset
      depression.

PMID- 16579720
TI  - Sleep practices, attitudes, and beliefs in inner city middle school children: a
      mixed-methods study.
AB  - The objective of this study was to utilize both semi-quantitative and qualitative
      data to examine the sociodemographic, social environmental, and behavioral
      context of sleep practices in a group of 64 middle school students enrolled in a
      summer camp program. Participants completed the Sleep Habits Survey; semi
      structured interviews were used to collect data regarding sleep knowledge,
      perceived barriers to healthy sleep, consequences of inadequate sleep, sources of
      sleep information, and suggestions for improved sleep. Environmental and social
      factors figured prominently as perceived barriers to healthy sleep. Many of the
      respondents mentioned adult guidance regarding sleep habits as potentially
      helpful. Identification of predictive factors for insufficient sleep may be
      helpful in developing interventions to change sleep health risk behaviors in
      middle school populations.

PMID- 16579721
TI  - Production and processing of soybeans and nutrition and safety of isoflavone and
      other soy products for human health.
AB  - Functional foods are intended to help consumers reduce or manage the risks for
      certain diseases while maintaining body function and structure. Functional foods
      are regulated differently depending upon the country. For example, the United
      States has not defined the term functional food in regulation. Thus, functional
      foods are treated just like conventional foods for obtaining regulatory safety
      approval. However, the sales of soy products, soy-enriched foods, and dietary
      supplements have grown tremendously during the past 3 years because of the
      increasing consumer awareness of soy as a healthy food ingredient. Isoflavones in
      soy are believed to have preventive effects for several hormone-dependent
      diseases, mainly due to their weak estrogenic activity. This mini-review
      discusses some of the important issues to be considered in using soy and
      isoflavone products as health foods, including production, composition, products,
      and processing of soy products, and the fate of isoflavones during processing,
      their bioavailability, and safety. Some of these issues may affect the choice of
      raw or basic material sources, processing conditions, quality control
      procedures/measures, and marketing strategies for both soy-based foods and
      isoflavones.

PMID- 16579722
TI  - Resveratrol and its glycon piceid are stable polyphenols.
AB  - Plant extracts containing phytopolyphenols, including resveratrol, are
      extensively used as nutraceutical supplements. Recent reports allege their lack
      of stability at ambient conditions. We have studied the stability of resveratrol
      and its glycon piceid in a mixture with a whole grape extract for 2 years (long
      term stability) under Good Manufacturing Practice pharmaceutical protocols (at
      60% humidity and 25 degrees C). The neat compounds were followed for 4 years
      under conditions of "accelerated stability," at 75% humidity and 40 degrees C,
      all in the presence of ambient air. Chromatographic analysis did not detect any
      instability, thus disproving the claims to the opposite. No storage precautions
      are necessary for these nutritional supplements.

PMID- 16579723
TI  - Antiobesity effect of Kochujang (Korean fermented red pepper paste) extract in
      3T3-L1 adipocytes.
AB  - Kochujang (Korean fermented red pepper paste) is a mixture of fermented soybeans,
      wheat, and red pepper powder. Kochujang has been reported to reduce body fat gain
      and lipid levels of adipose tissues and serum in rats. We studied the inhibitory
      effect of Kochujang on lipid accumulation and investigated the molecular
      mechanism of the action in 3T3-L1 adipocytes by measuring the expression levels
      of adipocyte-specific genes by real-time reverse transcription-polymerase chain
      reaction. When 3T3-L1 adipocytes were treated with Kochujang extract (KE), the
      sizes of adipocytes and leptin secretion were decreased. Hormone-sensitive lipase
      (HSL) was transcriptionally up-regulated at 4 hours, and glycerol secretion was
      increased at both 4 hours and 24 hours. Moreover, mRNA expression levels of both
      sterol regulatory element-binding protein 1-c (SREBP-1c) and peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma), which are critical
      transcription factors for adipogenesis, were markedly down-regulated. Tumor
      necrosis factor-alpha (TNF-alpha) is reported to impair pre-adipocyte
      differentiation and induce lipolysis and apoptosis. KE treatment of 3T3-L1
      adipocytes decreased TNF-alpha mRNA levels, but had no apparent affect on
      apoptosis. Taken together, our study shows that Kochujang decreased lipid
      accumulation in 3T3-L1 adipocytes by inhibiting adipogenesis through down
      regulation of SREBP-1c and PPAR-gamma and by stimulation of lipolysis due to
      increased HSL activity. TNF-alpha might not be involved in the reduction of lipid
      accumulation by KE.

PMID- 16579724
TI  - Dietary trans-10, cis-12 and cis-9,trans-11 conjugated linoleic acids induce
      apoptosis in the colonic mucosa of rats treated with 1,2-dimethylhydrazine.
AB  - We have previously shown that a diet containing a mixture of conjugated linoleic
      acid (CLA) isomers reduces the incidence of colon tumors in rats treated with 1,2
      dimethylhydrazine (DMH). The present study examined which of the two main CLA
      isomers, trans-10,cis-12 CLA (t10c12) or cis-9,trans-11 CLA (c9t11), decreases
      colon tumor numbers and the mechanisms for this effect. Six-week-old, male
      Sprague-Dawley rats were intramuscularly injected with 15 mg/kg of DMH twice per
      week for 6 weeks and fed a control diet, 1% t10c12, or 1% c9t11 for 30 weeks. The
      experimental diets were initiated simultaneously with DMH injection. The tumor
      numbers were decreased and the apoptotic index was significantly increased in the
      colonic mucosa of the t10c12 and c9t11 groups, when the results were compared
      with those of the control group. The protein levels of Bcl-2 and cyclooxygenase-2
      were significantly decreased, but Bax levels were increased in both of the CLA
      isomer groups. The thromboxane B(2) levels in colonic mucosa were substantially
      lower in the two CLA isomer groups than in the control group. However, there was
      no difference in these parameters between the CLA isomer groups. We have
      demonstrated that diets containing 1% t10c12 and c9t11 were equally effective in
      reducing tumor numbers and inducing apoptosis in the colonic mucosa of rats
      treated with DMH. These results indicate that Bcl-2 family protein levels are
      associated with CLA-induced apoptosis in the colonic mucosa of DMH-treated rats.

PMID- 16579725
TI  - Genistein induces glucose-regulated protein 78 in mammary tumor cells.
AB  - Preliminary studies have shown that genistein modulates the expression of some
      heat shock proteins in mammary tumor cells. In this study, we investigated the
      effect of genistein pretreatment on the expression of glucose-regulated protein
      78 (GRP78) in both estrogen receptor-positive (MCF-7) and -negative (MDA-MB-231)
      cells. Genistein increased the expression of GRP78 in a dose- and time-dependent
      manner and suppressed glucose uptake in both cell lines. However, induction of
      GRP78 by genistein appears not to be directly associated with inhibition of
      glucose uptake. Genistein treatment also made MDA-MB-231 cells more sensitive to
      doxorubicin, probably via increased GRP78 expression, but had no effect or even
      decreased drug sensitivity in MCF-7 cells. These results suggest that genistein
      may be exploited as an enhancer of chemotherapeutic agents in certain types of
      breast cancer.

PMID- 16579726
TI  - Taurine-responsive genes related to signal transduction as identified by cDNA
      microarray analyses of HepG2 cells.
AB  - Taurine-induced changes in the expression profiles of HepG2 cells were assessed
      using a cDNA microarray technology, and confirmed by real-time reverse
      transcription-polymerase chain reaction (RT-PCR) analyses. Of 8,298 human genes
      on the microarray, 128 genes (87 known genes) were up-regulated, and 349 (206
      known genes) were down-regulated more than 2.0-fold by taurine. Among the 293
      known genes regulated by taurine, a total of 44 genes were involved in signal
      transduction; 16 genes were up-regulated greater than 2.0-fold, and 28 genes were
      down-regulated more than 2.0-fold by taurine. The results of RT-PCR analyses for
      the five genes selected were consistent with our microarray data, although the
      fold changes in the expression level differed somewhat between the two analytical
      methods. Among signal transduction-related genes affected by taurine, four genes-
      mitogen-activated protein kinase (MAPK) kinase kinase 7, p21-activated kinase 4,
      sprouty homolog 2, and MAPK kinase 1--are implicated in the MAPK signaling
      pathway. Taurine also regulated the expression of signal transducer and activator
      of transcription (STAT) 3 gene involved in the Janus kinase-STAT pathway, and
      diacylglycerol kinase, zeta 104 kDa, the downstream mediator of the protein
      kinase C transmembrane signaling pathway. In conclusion, gene expression
      profiling of HepG2 cells treated with taurine provided us with new insights into
      the novel aspects of taurine as a possible regulator of MAPK signaling cascades
      and protein kinase C signaling pathways involved in cellular processes such as
      cell growth, differentiation, and apoptosis.

PMID- 16579727
TI  - Antioxidant activity of far-infrared radiated rice hull extracts on reactive
      oxygen species scavenging and oxidative DNA damage in human lymphocytes.
AB  - The antioxidant activities of methanolic extracts of far-infrared irradiated rice
      hull (FRH) and non-irradiated intact rice hull (IRH) were determined. The
      antioxidant effects against reactive oxygen species (ROS) were evaluated by
      measuring scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical, superoxide, hydrogen peroxide (H2O2), and nitric oxide radical and
      capacity for chelating metals. Except for H2O2 scavenging activity, FRH showed
      higher scavenging activity than IRH; for example, the 50% inhibitory
      concentration (mg/mL) values for DPPH radical scavenging of FRH and IRH were
      0.067 and 0.085, respectively, as compared with 0.362 and 0.012 for butylated
      hydroxytoluene and alpha-tocopherol, respectively. The effect of rice hull
      extract on DNA damage induced by H2O2 in human lymphocytes was also evaluated by
      comet assay. The protective effect of rice hull extract increased as its
      concentration increased from 12.5 to 50 microg/mL, as indicated by DNA strand
      breakage decreasing from 38% to 22% with FRH and from 49% to 28% with IRH as
      compared with H2O2-treated positive controls. When human lymphocytes were post
      incubated with rice hull extract for 30 minutes after exposure to H2O2, the
      protective ability of the rice hulls remained unchanged. These results suggest
      that methanol extracts of rice hulls possess significant ROS scavenging and metal
      chelating activities and protective effect against oxidative DNA damage.

PMID- 16579728
TI  - The effects of grapefruit on weight and insulin resistance: relationship to the
      metabolic syndrome.
AB  - To study the effects of grapefruit and grapefruit products on body weight and
      metabolic syndrome, 91 obese patients were randomized to either placebo capsules
      and 7 ounces (207 mL) of apple juice, grapefruit capsules with 7 ounces (207 mL)
      of apple juice, 8 ounces (237 mL) of grapefruit juice with placebo capsule, or
      half of a fresh grapefruit with a placebo capsule three times a day before each
      meal. Metabolic syndrome parameters were measured at the beginning and end of 12
      weeks. After 12 weeks, the fresh grapefruit group had lost 1.6 kg, the grapefruit
      juice group had lost 1.5 kg, the grapefruit capsule group had lost 1.1 kg, and
      the placebo group had lost 0.3 kg. The fresh grapefruit group lost significantly
      more weight than the placebo group (P < .05). A secondary analysis of those with
      the metabolic syndrome in the four treatment groups demonstrated a significantly
      greater weight loss in the grapefruit, grapefruit capsule, and grapefruit juice
      groups compared with placebo (P < .02). There was also a significant reduction in
      2-hour post-glucose insulin level in the grapefruit group compared with placebo.
      Half of a fresh grapefruit eaten before meals was associated with significant
      weight loss. In metabolic syndrome patients the effect was also seen with
      grapefruit products. Insulin resistance was improved with fresh grapefruit.
      Although the mechanism of this weight loss is unknown it would appear reasonable
      to include grapefruit in a weight reduction diet.

PMID- 16579729
TI  - Antiproliferative activities of parthenolide and golden feverfew extract against
      three human cancer cell lines.
AB  - The medicinal herb feverfew [Tanacetum parthenium (L.) Schultz-Bip.] has long
      been used as a folk remedy for the treatment of migraine and arthritis.
      Parthenolide, a sesquiterpene lactone, is considered to be the primary bioactive
      compound in feverfew having anti-migraine, anti-tumor, and anti-inflammatory
      properties. In this study we determined, through in vitro bioassays, the
      inhibitory activity of parthenolide and golden feverfew extract against two human
      breast cancer cell lines (Hs605T and MCF-7) and one human cervical cancer cell
      line (SiHa). Feverfew ethanolic extract inhibited the growth of all three types
      of cancer cells with a half-effective concentration (EC50) of 1.5 mg/mL against
      Hs605T, 2.1 mg/mL against MCF-7, and 0.6 mg/mL against SiHa. Among the tested
      constituents of feverfew (i.e., parthenolide, camphor, luteolin, and apigenin),
      parthenolide showed the highest inhibitory effect with an EC50 against Hs605T,
      MCF-7, and SiHa of 2.6 microg/mL, 2.8 microg/mL, and 2.7 microg/mL, respectively.
      Interactions between parthenolide and flavonoids (apigenin and luteolin) in
      feverfew extract also were investigated to elucidate possible synergistic or
      antagonistic effects. The results revealed that apigenin and luteolin might have
      moderate to weak synergistic effects with parthenolide on the inhibition of
      cancer cell growth of Hs605T, MCF-7, and SiHa.

PMID- 16579730
TI  - Analysis of responses to kava kava in the feline pulmonary vascular bed.
AB  - This study was designed to test the hypothesis that kava kava induces a depressor
      response in the pulmonary vascular bed of the cat and to identify the pathways
      involved in the mediation or modulation of these effects. In separate
      experiments, the effects of L-N5-(1-iminoethyl)ornithine hydrochloride (L-NIO), a
      nitric oxide synthase inhibitor, glibenclamide, an ATP-sensitive K+ channel
      blocker, meclofenamate, a nonselective cyclooxygenase inhibitor, nicardipine, a
      calcium channel blocker, bicuculline, a gamma-aminobutyric acid (GABA)A receptor
      antagonist, and saclofen, a GABAB antagonist, were investigated on pulmonary
      arterial responses to kava kava (kava), pinacidil, an ATP-sensitive K+ channel
      activator, bradykinin, an inducer of nitric oxide synthase, 3
      aminopropyl(methyl)phosphinic acid hydrochloride (SKF-97541), a GABAB receptor
      agonist, and muscimol, a GABAA receptor agonist. Lobar arterial perfusion
      pressure and systemic pressure were continuously monitored, electronically
      averaged, and recorded. Under elevated tone conditions in the isolated left lower
      lobe of the feline vascular bed, kava induced a dose-dependent vasodepressor
      response that was not significantly altered after administration of L-NIO,
      glibenclamide, meclofenamate, or saclofen. Responses to kava were significantly
      reduced after administration of either nicardipine or bicuculline. When the
      calcium channel blocker nicardipine was administered in addition to the GABA
      blocker bicuculline, there was near complete attenuation of the kava-induced
      vasodepressor responses. The results of this investigation suggest that kava has
      potent vasodepressor activity in the feline lung bed and that this response is
      mediated or modulated by both a calcium channel- and GABA receptor-sensitive
      pathway.

PMID- 16579731
TI  - Influence of concomitant food intake on the excretion of orally administered myo
      inositol hexaphosphate in humans.
AB  - myo-Inositol hexaphosphate (InsP6) widely occurs in plant seeds. At present, some
      important benefits of InsP6 for human health have been described. The purpose of
      this study was to find the best condition for the optimum absorption of orally
      administered InsP6, evaluated by InsP6 urinary excretion. The influence of
      different stomach conditions (empty, empty with an alkalinizing agent, and full
      stomach) on the effects of oral administration of InsP6 and its urinary excretion
      was investigated in six healthy subjects on an InsP6-poor diet, given 400 mg of
      calcium/magnesium salt of InsP6 as a single dose. The basal urinary excretion of
      InsP6 on an InsP6-poor diet (50.91 +/- 15.09 microg) was significantly lower than
      that found when an InsP6-normal diet was consumed (100.09 +/- 26.42 microg) (P <
      .05). No differences were observed in the areas under the curve of accumulated
      excretion at 8 hours among the three different stomach conditions studied,
      suggesting that the overall InsP6 absorption took place independently of the
      stomach state (full or fasted) and indicating that the InsP6 absorption also
      takes place during the intestinal transit. Thus, if InsP6 supplements of vegetal
      origin are consumed to maintain the optimum InsP6 levels needed for a healthy
      status, these supplements can be consumed either during or between meals with the
      same efficacy.

PMID- 16579732
TI  - Effect of vitamin E on lipid parameters in ovariectomized rats.
AB  - The risk of cardiovascular disease drastically increases at the onset of
      menopause, in part, because of rise in blood cholesterol and unfavorable changes
      in lipid profile. This study was designed to investigate the dose-dependent
      effects of vitamin E supplementation on lipid parameters in ovariectomized (ovx)
      rats. Sixty 12-month-old female Sprague-Dawley rats were either sham-operated
      (sham; one group) or ovx (four groups). All rats were maintained on a
      semipurified caseinbased diet (AIN-93M; 75 IU vitamin E/kg of diet) for a period
      of 120 days. Thereafter, ovx rats were placed on one of four doses of vitamin E
      treatment (75, 300, 525, or 750 IU vitamin E/kg of diet), while the sham group
      was continued on 75 IU vitamin E/kg of diet for 100 days. Ovariectomy tended to
      increase (by 24%, P = 0.1) serum non?high-density lipoprotein (HDL) cholesterol
      and decrease (by 14%, P = 0.1) HDL cholesterol. Vitamin E did not have any
      significant effects on serum lipid parameters. Liver total lipids were notably
      increased (P < .001) in ovx animals, and supplementation with vitamin E at 525
      IU/kg of diet was able to significantly reduce liver total lipids by 13%.
      Additionally, ovariectomy caused an increase in serum glucose and liver C18:1
      fatty acid concentrations along with decreases in C18:0, C20:4, and C22:6 fatty
      acid concentrations. These alterations on liver fatty acid profiles were
      unaffected by vitamin E. The findings of this study suggest that vitamin E
      supplementation moderately improves lipid parameters in ovarian hormone-deficient
      rats.

PMID- 16579734
TI  - Alpha-ketoglutarate modulates the circadian patterns of lipid peroxidation and
      antioxidant status during N-nitrosodiethylamine-induced hepatocarcinogenesis in
      rats.
AB  - The effect of alpha-ketoglutarate (alpha-KG) on circadian patterns of lipid
      peroxides and antioxidants in N-nitrosodiethylamine (NDEA)-induced
      hepatocarcinogenesis in rats has been studied. The circadian rhythm
      characteristics (acrophase, amplitude, and mesor) of thiobarbituric acid-reactive
      substances (TBARS), antioxidants, superoxide dismutase, catalase, glutathione
      peroxidase, and reduced glutathione were markedly altered in NDEA-treated rats.
      The delays in acrophase observed in NDEA-treated rats were brought back to near
      normal range by the administration of alpha-KG. An increase in mesor values of
      TBARS and a decrease in mesor values of antioxidants in NDEA-administered rats
      were reversed by alpha-KG administration. It can be concluded that alpha-KG
      exerts its chemopreventive effect by restoring antioxidants and their circadian
      rhythms.

PMID- 16579733
TI  - Antidepressant-like activity of n-hexane extract of nutmeg (Myristica fragrans)
      seeds in mice.
AB  - The present study was undertaken to investigate the effect of an n-hexane extract
      of Myristica fragrans seeds on depression in mice by using the forced swim test
      (FST) and the tail suspension test (TST). M. fragrans extract (5, 10, and 20
      mg/kg) was administered orally for 3 successive days to different groups of Swiss
      male young albino mice. M. fragrans extract significantly decreased immobility
      periods of mice in both the FST and the TST. The 10 mg/kg dose was found to be
      most potent, as indicated by the greatest decrease in the immobility period
      compared with the control. Furthermore, this dose of the extract was found to
      have comparable potency to imipramine (15 mg/kg i.p.) and fluoxetine (20 mg/kg
      i.p.). The extract did not have a significant effect on locomotor activity of
      mice. Prazosin (62.5 microg/kg i.p.; an alpha (1)-adrenoceptor antagonist),
      sulpiride (50 mg/kg i.p.; a selective D(2) receptor antagonist), and p
      chlorophenylalanine (100 mg/kg i.p.; an inhibitor of serotonin synthesis)
      significantly attenuated the M. fragrans extract-induced antidepressant-like
      effect in the TST. Thus, extract of M. fragrans elicited a significant
      antidepressant-like effect in mice, when assessed in both the TST and the FST.
      The antidepressant-like effect of the extract seems to be mediated by interaction
      with the adrenergic, dopaminergic, and serotonergic systems.

PMID- 16579735
TI  - Hypolipidemic activity of Allium porrum L. in cholesterol-fed rabbits.
AB  - Allium porrum L. is a herbaceous plant from the Liliaceae family and has been
      widely used in Persian foods as a flavor component and in Iranian traditional
      medicine as an anti-atherogenic remedy. The present investigation was undertaken
      to evaluate the antihypercholesterolemic effect of a hydroalcoholic extract of A.
      porrum L. bulbs. Rabbits were divided into five groups--control,
      hypercholesterolemic control, and three treatment groups (hypercholesterolemic
      diet + 250, 500, or 1,000 mg/kg of body weight of extract, respectively)--and
      were fed for 12 weeks. Blood samples were obtained to analyze plasma cholesterol,
      triglycerides, and low-density lipoprotein (LDL), very LDL, and high-density
      lipoprotein (HDL) cholesterol. Body weight increased in all groups throughout the
      treatment without significant differences among them. Plasma total cholesterol
      increased with respect to the control in the positive control group at the end of
      the treatment. Plasma total cholesterol decreased in all groups treated with A.
      porrum extract in a dose-dependent fashion. Changes in the distribution of
      cholesterol in HDL or LDL were found, and LDL cholesterol decreased significantly
      in all of the groups treated with A. porrum extract with respect to the
      hypercholesterolemic group. Thus, these findings indicate that this plant may be
      useful for the treatment of hypercholesterolemia.

PMID- 16579736
TI  - Antihyperlipidemic effect of Scoparia dulcis (sweet broomweed) in streptozotocin
      diabetic rats.
AB  - We have investigated Scoparia dulcis, an indigenous plant used in Ayurvedic
      medicine in India, for its possible antihyperlipidemic effect in rats with
      streptozotocin-induced experimental diabetes. Oral administration of an aqueous
      extract of S. dulcis plant (200 mg/kg of body weight) to streptozotocin diabetic
      rats for 6 weeks resulted in a significant reduction in blood glucose, serum and
      tissue cholesterol, triglycerides, free fatty acids, phospholipids, 3-hydroxy-3
      methylglutaryl (HMG)-CoA reductase activity, and very low-density lipoprotein and
      low-density lipoprotein cholesterol levels. The decreased serum high-density
      lipoprotein cholesterol, anti-atherogenic index, and HMG-CoA reductase activity
      in diabetic rats were also reversed towards normalization after the treatment.
      Similarly, the administration of S. dulcis plant extract (SPEt) to normal animals
      resulted in a hypolipidemic effect. The effect was compared with glibenclamide
      (600 microg/kg of body weight). The results showed that SPEt had
      antihyperlipidemic action in normal and experimental diabetic rats in addition to
      its antidiabetic effect.

PMID- 16579737
TI  - Antihyperglycemic activity of Piper betle leaf on streptozotocin-induced diabetic
      rats.
AB  - Piper betle, an indigenous medicinal plant, has a folk (Siddha and Ayurvedha)
      reputation in the rural southern India. The present study was carried out to
      evaluate the effect of P. betle on glucose metabolism since it is consumed as
      betel-quid after meals. Plasma levels of glucose and glycosylated hemoglobin and
      activities of liver hexokinase and gluconeogenic enzymes such as glucose-6
      phosphatase and fructose-1,6-bisphosphatase in control and streptozotocin (STZ)
      diabetic rats were assayed. Oral administration of leaf suspension of P. betle
      (75 and 150 mg/kg of body weight) for 30 days resulted in significant reduction
      in blood glucose (from 205.00 +/- 10.80 mg/dL to 151.30 +/- 6.53 mg/dL) and
      glycosylated hemoglobin and decreased activities of liver glucose-6-phosphatase
      and fructose-1,6-bisphosphatase, while liver hexokinase increased (P < .05), in
      STZ diabetic rats when compared with untreated diabetic rats. P. betle at a dose
      of 75 mg/kg of body weight exhibited better sugar reduction than 150 mg/kg of
      body weight. In addition, protection against body weight loss of diabetic animals
      was also observed. The effects produced by P. betle were compared with the
      standard drug glibenclamide. Thus, the present study clearly shows that P. betle
      intake influences glucose metabolism beneficially.

PMID- 16579738
TI  - Nardostachys jatamansi improves learning and memory in mice.
AB  - Cure of cognitive disorders such as amnesia, attention deficit, and Alzheimer's
      disease is still far from being realized in the field of medicine. Nootropic
      agents such as piracetam, aniracetam, and choline esterase inhibitors like
      donepezil are being used for improving memory, mood, and behavior, but the
      resulting side effects associated with these agents have made their applicability
      limited. In Ayurveda, the roots of Nardostachys jatamansi have been clinically
      employed for their anti-ischemic, antioxidant, anticonvulsant, and
      neuroprotective activities. The present study was undertaken to assess the
      potential of N. jatmansi as a memory enhancer. The elevated plus maze and the
      passive avoidance paradigm were employed to evaluate learning and memory
      parameters. Three doses (50, 100, and 200 mg/kg, p.o.) of an ethanolic extract of
      N. jatamansi were administered for 8 successive days to both young and aged mice.
      The 200 mg/kg dose of N. jatmansi ethanolic extract significantly improved
      learning and memory in young mice and also reversed the amnesia induced by
      diazepam (1 mg/kg, i.p.) and scopolamine (0.4 mg/kg, i.p.). Furthermore, it also
      reversed aging-induced amnesia due to natural aging of mice. As scopolamine
      induced amnesia was reversed, it is possible that the memory improvement may be
      because of facilitation of cholinergic transmission in the brain. Hence, N.
      jatmansi might prove to be a useful memory restorative agent in the treatment of
      dementia seen in elderly persons. The underlying mechanism of action can be
      attributed to its antioxidant property.

PMID- 16579739
TI  - Beware of pomegranates bearing 40% ellagic Acid.
AB  - A recent profusion of pomegranate nutraceutical products, "standardized to 40%
      ellagic acid," has appeared in the marketplace. This Perspective reviews the
      chemical and functional studies of pomegranate as well as the virtues and dangers
      of ellagic acid, and concludes that synergy among the various pomegranate
      fractions and phytochemicals is the most important factor for assessing strength
      of pomegranate nutraceutical preparations, and not simply the concentration of
      ellagic acid. Ellagic acid concentration in final products is likely to have an
      optimal therapeutic range, which very likely is less than 40%. The wisdom of
      designing and engineering pomegranate nutraceutical products to maximize
      therapeutic or chemopreventive synergy is suggested, as opposed to preparations
      that are designed and engineered simply to maximize the concentration of a single
      phytochemical. The implications of this strategy may be generalized for the
      optimization of nutraceutical preparations from other medicinal plants as well.

PMID- 16579740
TI  - Determination of minerals extracted from several commercial teas (Camellia
      sinensis) to hot water (infusion).
AB  - Mineral contents of some tea and their infusions drunk in Turkey were established
      by inductively coupled plasma atomic emission spectrometry. The Al, Ca, K, Mg,
      Mn, P, and S contents were very high in both infusions and tea (i.e., pieces of
      the tea plant). The As, Cd, Cr, Li, Pb, and Se contents of infusion and tea were
      found to be very low. The level of K of all samples is higher than those of other
      minerals. Generally, mineral contents of tea were found to be higher than those
      of tea infusions. In addition, the health benefits of teas and knowledge of their
      mineral contents are of great interest and may be useful for further study of
      enzyme systems and vital biochemical functions.

PMID- 16579741
TI  - Constituents of the essential oil of sea fennel (Crithmum maritimum L.) growing
      wild in Turkey.
AB  - The essential oils isolated by hydrodistillation from freshly obtained aerial
      parts of sea fennel (Crithmum maritimum L.) were found to be a yellow liquid,
      obtained in a yield of 0.2% (vol/wt) based on wet weight. The essential oils
      obtained from young leaves and branches of C. maritimum, collected at two
      different locations in Turkey (Sipahili and Yesilovacik), were analyzed by gas
      chromatography-mass spectrometry. Twenty-three components were identified
      accounting for more than 99% of the total oils. The oils contained mainly
      monoterpenes, amounting to 89.0% and 99.6%, respectively, of the oils, with gamma
      terpinene (36% and 32%), beta-phellandrene (21% and 22%), and sabinene (13% and
      9%) as the main components.

PMID- 16579742
TI  - On the bioequivalence and bioavailability of three coenzyme Q10 products.

PMID- 16579744
TI  - Vaccines and veterinarians to tackle the spread of avian influenza.

PMID- 16579745
TI  - Use of force plate analysis to assess the analgesic effects of etodolac in horses
      with navicular syndrome.
AB  - OBJECTIVE: To evaluate the musculoskeletal analgesic effect of etodolac
      administered PO every 12 or 24 hours in chronically lame horses by use of force
      plate analysis. ANIMALS: 22 horses with navicular syndrome. PROCEDURE: Horses
      received etodolac (23 mg/kg, PO, q 12 h; n = 7), etodolac (23 mg/kg, PO, q 24 h;
      8), or corn syrup (20 mL, PO, q 24 h; control treatment; 7) for 3 days. Combined
      forelimb peak vertical ground reaction force (PVF) was measured via force plate
      analysis before the first treatment (baseline) and at 6, 12, 24, and 36 hours
      after the last treatment. Differences in mean PVF (mPVF) between baseline and
      subsequent measurements were analyzed (repeated-measures ANOVA) and evaluated for
      treatment and time effects and treatment-time interaction. RESULTS: Once- or
      twice-daily administration of etodolac resulted in significant increases in mPVF
      from baseline at 6, 12, and 24 hours after the last treatment, compared with the
      control treatment. There were no significant differences in mPVF between the
      etodolac treatment groups at any time point. In both etodolac treatment groups,
      there was a significant increase in mPVF from baseline at 6, 12, and 24 hours,
      compared with that at 36 hours. Etodolac-associated adverse effects were not
      detected. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with navicular syndrome,
      once-daily oral administration of 23 mg of etodolac/kg appears to provide
      effective analgesia for as long as 24 hours. Twice-daily administration of
      etodolac at this same dose does not appear to provide any additional analgesic
      efficacy or duration of effect.

PMID- 16579746
TI  - In vitro efficacy of a buffered chelating solution as an antimicrobial
      potentiator for antifungal drugs against fungal pathogens obtained from horses
      with mycotic keratitis.
AB  - OBJECTIVE: To determine whether a novel third-generation chelating agent (8 mM
      disodium EDTA dehydrate and 20 mM 2-amino-2-hydroxymethyl-1, 3-propanediol) would
      act as an antimicrobial potentiator to enhance in vitro activity of antifungal
      medications against fungal isolates obtained from horses with mycotic keratitis.
      SAMPLE POPULATION: Fungal isolates (3 Aspergillus isolates, 5 Fusarium isolates,
      1 Penicillium isolate, 1 Cladosporium isolate, and 1 Curvularia isolate) obtained
      from horses with mycotic keratitis and 2 quality-control strains obtained from
      the American Type Culture Collection (ATCC; Candida albicans ATCC 90028 and
      Paecilomyces variotii ATCC 36257). PROCEDURE: Minimum inhibitory concentrations
      (MICs) against fungal isolates for 4 antifungal drugs (miconazole, ketoconazole,
      itraconazole, and natamycin) were compared with MICs against fungal isolates for
      the combinations of each of the 4 antifungal drugs and the chelating agent. The
      Clinical and Laboratory Standards Institute microdilution assay method was
      performed by use of reference-grade antifungal powders against the fungal
      isolates and quality-control strains of fungi. RESULTS: Values for the MIC at
      which the antifungal drugs decreased the growth of an organism by 50% (MIC50) and
      90% (MIC90) were decreased for the control strains and ophthalmic fungal isolates
      by 50% to 100% when the drugs were used in combination with the chelating agent
      at a concentration of up to 540 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE:
      The chelating agent increased in vitro activity of antifungal drugs against
      common fungal pathogens isolated from eyes of horses with mycotic keratitis.

PMID- 16579747
TI  - Effects of doxycycline, amoxicillin, cephalexin, and enrofloxacin on hemostasis
      in healthy dogs.
AB  - OBJECTIVE: To determine the effects of enteral administration of doxycycline,
      amoxicillin, cephalexin, and enrofloxacin at therapeutic dosages for a typical
      duration on hemostatic variables in healthy dogs. ANIMALS: 14 Beagles. PROCEDURE:
      Doxycycline (10 mg/kg, PO, q 12 h), amoxicillin (30 mg/kg, PO, q 12 h),
      cephalexin (30 mg/kg, PO, q 12 h), and enrofloxacin (20 mg/kg, PO, q 24 h) were
      administered in random order to 10 healthy dogs at standard therapeutic dosages
      for 7 days, with a 7-day washout period between subsequent antimicrobials. In
      addition, 4 Beagles served as control dogs. Variables were evaluated before and
      after antimicrobial administration; they included platelet count, Hct, 1-stage
      prothrombin time (PT), activated partial thromboplastin time (PTT), fibrinogen
      concentration, and platelet function. Platelet function was assessed via buccal
      mucosal bleeding time, aggregation, and a platelet-function analyzer. RESULTS:
      Administration of all antimicrobials caused a slight prolongation of 1-stage PT
      and activated PTT and slight decrease in fibrinogen concentration. Cephalexin
      caused a significant increase in 1-stage PT and activated PTT, amoxicillin caused
      a significant increase in activated PTT, and enrofloxacin caused a significant
      decrease in fibrinogen concentration. Platelet count or function did not differ
      significantly after administration of any antimicrobial. CONCLUSIONS AND CLINICAL
      RELEVANCE: Oral administration of commonly used antimicrobials in healthy dogs
      resulted in minor secondary hemostatic abnormalities, with no change in platelet
      count or function. Although these changes were clinically irrelevant in healthy
      dogs, additional studies of the effects of antimicrobial administration on
      hemostasis in animals with underlying disease processes are warranted.

PMID- 16579749
TI  - Hemodynamic effects of methylprednisolone acetate administration in cats.
AB  - OBJECTIVE: To investigate the mechanisms by which corticosteroid administration
      may predispose cats to congestive heart failure (CHF). ANIMALS: 12 cats receiving
      methylprednisolone acetate (MPA) for the treatment of dermatologic disorders.
      PROCEDURE: The study was conducted as a repeated-measures design. Various
      baseline variables were measured, after which MPA (5 mg/kg, IM) was administered.
      The same variables were then measured at 3 to 6 days and at 16 to 24 days after
      MPA administration. Evaluations included physical examination, systolic blood
      pressure measurement, hematologic analysis, serum biochemical analysis, thoracic
      radiography, echocardiography, and total body water and plasma volume
      determination. RESULTS: MPA resulted in a substantial increase in serum glucose
      concentration at 3 to 6 days after administration. Concurrently, RBC count, Hct,
      and hemoglobin concentration as well as serum concentrations of the major
      extracellular electrolytes, sodium and chloride, decreased. Plasma volume
      increased by 13.4% (> 40% in 3 cats), whereas total body water and body weight
      slightly decreased. All variables returned to baseline by 16 to 24 days after MPA
      administration. CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that MPA
      administration in cats causes plasma volume expansion as a result of an intra to
      extracellular fluid shift secondary to glucocorticoid-mediated extracellular
      hyperglycemia. This mechanism is analogous to the plasma volume expansion that
      accompanies uncontrolled diabetes mellitus in humans. Any cardiovascular
      disorders that impair the normal compensatory mechanisms for increased plasma
      volume may predispose cats to CHF following MPA administration.

PMID- 16579748
TI  - Histomorphologic evaluation of extracorporeal shock wave therapy of the fourth
      metatarsal bone and the origin of the suspensory ligament in horses without
      lameness.
AB  - OBJECTIVE: To determine via histologic examination and scintigraphy the effect of
      focused extracorporeal shock wave therapy (ESWT) on normal bone and the bone
      ligament interface in horses. ANIMALS: 6 horses without lameness. PROCEDURE:
      Origins of the suspensory ligament at the metacarpus (35-mm probe depth) and
      fourth metatarsal bone (5-mm probe depth) were treated twice (days 0 and 16) with
      2,000 shocks (energy flux density, 0.15 mJ/mm2). One forelimb and 1 hind limb
      were randomly treated, and the contralateral limbs served as nontreated controls.
      Bone scans were performed on days -1 (before ESWT), 3, 16, and 19.
      Histomorphologic studies of control and treated tissues were performed on day 30.
      RESULTS: ESWT significantly increased the number of osteoblasts but caused no
      damage to associated soft tissue structures and did not induce cortical
      microfractures. A significant correlation between osteoblast numbers and
      radiopharmaceutical uptake was noticed on lateral views of the hind limb on days
      3 and 16 and on caudal views of the forelimb on day 3. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that ESWT has the potential to increase osteoblast
      numbers in horses. The correlation between increased osteoblast numbers and radio
      pharmaceutical uptake 3 days and 16 days after the first ESWT suggested that
      stimulation of osteogenesis occurred soon after ESWT. No damage to bone or the
      bone-ligament interface should occur at the settings used in this study, and ESWT
      can therefore be administered safely in horses.

PMID- 16579750
TI  - In vitro evaluation of the effect of a novel immunosuppressive agent, FTY720, on
      the function of feline neutrophils.
AB  - OBJECTIVE: To use in vitro assays to evaluate the effects of a novel
      immunosuppressive agent, FTY720, on biological functions (migration,
      phagocytosis, and production of reactive-oxygen species [ROS]) of feline
      peripheral neutrophils and determine the cytotoxic effects of FTY720 on feline
      peripheral neutrophils. SAMPLE POPULATION: Peripheral neutrophils obtained from 8
      healthy cats. PROCEDURE: Peripheral neutrophils were isolated from blood samples
      obtained from the 8 cats and exposed to the phosphorylated form of FTY720 (FTY720
      P). A fluorescence-based in vitro evaluation of migration was performed.
      Phagocytosis of microbes and production of ROS were evaluated by use of a 2-color
      flow cytometry system. Samples of whole blood obtained from the cats were
      incubated with various concentrations of FTY720-P, fluorescein-labeled
      Staphylococcus aureus, and dihydroethidium. Cytotoxic effects were evaluated by
      use of propidium iodide staining. RESULTS: Addition of FTY720-P caused a slight
      non-significant decrease in phagocytosis and production of ROS by feline
      peripheral neutrophils. Migration activity of feline peripheral neutrophils was
      significantly increased by the addition of FTY720-P. Addition of FTY720-P at
      concentrations considered for clinical use did not increase the death rate of
      feline peripheral neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: FTY720 does
      not inhibit critical functions of feline peripheral neutrophils in vitro.

PMID- 16579751
TI  - Evaluation of assay procedures for prediction of passive transfer status in
      lambs.
AB  - OBJECTIVE: To compare 4 assay procedures for prediction of passive transfer
      status in lambs. ANIMALS: Thirty-one 1-day-old Sardinian lambs. PROCEDURE: Serum
      IgG concentration was determined by use of single radial immunodiffusion. The
      following were determined: serum total protein concentration as measured by
      refractometry (ie, refractometry serum total protein concentration), serum total
      protein concentration as determined by the biuret method (ie, biuret method serum
      total protein concentration), serum gamma-globulin concentration as determined by
      serum protein electrophoresis, and serum gamma-glutamyltransferase (GGT) activity
      as measured by spectrophotometry. Accuracy of these assays for estimation of
      serum IgG concentration in 1-day-old lambs was established by use of linear
      regression analysis. RESULTS: Refractometry serum total protein concentration,
      biuret method serum total protein concentration, and serum gamma-globulin
      concentration were closely and linearly correlated with serum IgG concentration.
      The natural logarithm (ln) of serum GGT activity was closely and linearly
      correlated with serum IgG concentration (ln). Refractometry serum total protein
      concentration, biuret method serum total protein concentration, and gamma
      globulin concentration accounted for approximately 85%, 91%, and 95% of the
      variation in serum IgG concentration, respectively. Serum GGT activity (ln)
      accounted for approximately 92% of the variation in serum IgG concentration (ln).
      CONCLUSIONS AND CLINICAL RELEVANCE: For prediction of passive transfer status in
      1-day-old lambs, serum GGT activity or biuret method serum total protein
      concentration determination will allow for passive transfer monitoring program
      development. Immediate refractometry serum total protein concentration
      determination is beneficial in making timely management and treatment decisions.
      Serum gamma-globulin concentration determination can be used as a confirmatory
      test.

PMID- 16579752
TI  - Effects of deracoxib and aspirin on serum concentrations of thyroxine, 3,5,3'
      triiodothyronine, free thyroxine, and thyroid-stimulating hormone in healthy
      dogs.
AB  - OBJECTIVE: To evaluate the effects of deracoxib and aspirin on serum
      concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), free thyroxine
      (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs. ANIMALS: 24 dogs.
      PROCEDURE: Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the
      vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg,
      PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h)
      for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were
      performed 7 days before treatment (day -7), on days 14 and 28 of treatment, and
      14 days after treatment was discontinued. Plasma total protein, albumin, and
      globulin concentrations were measured on days -7 and 28. RESULTS: Mean serum T4,
      fT4, and T3 concentrations decreased significantly from baseline on days 14 and
      28 of treatment in dogs receiving aspirin, compared with those receiving placebo.
      Mean plasma total protein, albumin, and globulin concentrations on day 28
      decreased significantly in dogs receiving aspirin, compared with those receiving
      placebo. Fourteen days after administration of aspirin was stopped, differences
      in hormone concentrations were no longer significant. Differences in serum TSH or
      the free fraction of T4 were not detected at any time. No significant difference
      in any of the analytes was detected at any time in dogs treated with deracoxib.
      CONCLUSIONS AND CLINICAL RELEVANCE: Aspirin had substantial suppressive effects
      on thyroid hormone concentrations in dogs. Treatment with high dosages of
      aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid
      function.

PMID- 16579753
TI  - Evaluation of historical factors influencing the occurrence and distribution of
      Mycobacterium bovis infection among wildlife in Michigan.
AB  - OBJECTIVES: To determine historical events leading to establishment of bovine
      tuberculosis in the white-tailed deer population in the northeastern corner of
      the lower peninsula (NELP) of Michigan and describe factors relevant to the
      present outbreak of bovine tuberculosis in Michigan. SAMPLE POPULATION: Cattle
      and white-tailed deer in Michigan from 1920 to 1990. PROCEDURES: A search of
      extant historical documents (eg, scientific journals, books, public reports, and
      correspondence and internal reports from governmental agencies) was conducted.
      Factors investigated included the number of cattle and prevalence of
      tuberculosis, deer population and density levels, and changes in regional
      environments affecting the population and management of cattle and wild deer.
      RESULTS: High deer numbers and severe winter feed shortages resulting from
      habitat destruction in the NELP in 1930 contributed to the transmission of
      tuberculosis from cattle to deer. Starvation increased the susceptibility of deer
      to infection and modified behavior such that exposure to infected cattle was
      increased. Relocation of deer resulted in spread of infection to other sites,
      including locations at which spatial clusters of tuberculosis presently exist.
      Ribotyping of Mycobacterium bovis from a human patient suggests that the strain
      of M. bovis presently infecting white-tailed deer in the region is the same
      strain that affected cattle farms at that time. CONCLUSIONS AND CLINICAL
      RELEVANCE: Feeding deer to maintain numbers above the normal carrying capacity of
      the NELP led to deer depending on consumption of livestock feed for survival
      during winter and increased contact with domestic cattle. This practice should be
      avoided.

PMID- 16579754
TI  - Associations among Listeria monocytogenes genotypes and distinct clinical
      manifestations of listeriosis in cattle.
AB  - OBJECTIVE: To determine whether specific strains of Listeria monocytogenes, as
      determined by genetic characteristics and virulence phenotypes, were associated
      with distinct clinical manifestations of listeriosis in cattle and thus may
      potentially have tissue specificity. ANIMALS: 32 cattle. PROCEDURE: DNA sequence
      data for the virulence genes actAand inlAwere used to infer the phylogeny of L.
      monocytogenes and to test for positive selection. Isolates were screened for the
      presence or absence of internalin genes and assigned an internalin profile.
      Plaquing assays were performed to determine the relative cytopathogenicity of
      each isolate. Categorical data analyses were performed to describe associations
      among L. monocytogenes genotypes, virulence phenotypes, and clinical
      manifestations of listeriosis. RESULTS: Results confirmed that L. monocytogenes
      represents 2 deeply separated evolutionary lineages. Genes actA and inlA
      contained amino acid sites under positive selection, and specific residues at
      some sites were associated with lineage and manifestation of listeriosis. Whereas
      lineage I was clonal and predominantly composed of isolates from cases of
      encephalitis, lineage II was more genetically diverse and equally represented by
      isolates from cases of encephalitis versus septicemia and fetal infection.
      Lineage I isolates also had greater cytopathogenicity in vitro, compared with
      lineage II isolates. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that
      L. monocytogenes virulence genes underwent positive selection that is consistent
      with the diversification of 2 evolutionary lineages: lineage I is clonal and
      associated with encephalitis, and lineage II is more genetically diverse and
      equally likely to cause both major forms of listeriosis in cattle.

PMID- 16579755
TI  - Analysis of genetic mutations in the 7a7b open reading frame of coronavirus of
      cheetahs (Acinonyx jubatus).
AB  - OBJECTIVE: To analyze the 7a7b genes of the feline coronavirus (FCoV) of
      cheetahs, which are believed to play a role in virulence of this virus. SAMPLE
      POPULATION: Biologic samples collected during a 4-year period from 5 cheetahs at
      the same institution and at 1 time point from 4 cheetahs at different
      institutions. PROCEDURES: Samples were first screened for FCoV via a reverse
      transcription-PCR procedure involving primers that encompassed the 3'
      untranslated region. Samples that yielded positive assay results were analyzed by
      use of primers that targeted the 7a7b open reading frames. The nucleotide
      sequences of the 7a7b amplification products were determined and analyzed.
      RESULTS: In most isolates, substantial deletional mutations in the 7a gene were
      detected that would result in aberrant or no expression of the 7a product because
      of altered reading frames. Although the 7b gene was also found to contain
      mutations, these were primarily point mutations resulting in minor amino acid
      changes. The coronavirus associated with 1 cheetah with feline infectious
      peritonitis had intact 7a and 7b genes. CONCLUSIONS AND CLINICAL RELEVANCE: The
      data suggest that mutations arise readily in the 7a region and may remain stable
      in FCoV of cheetahs. In contrast, an intact 7b gene may be necessary for in vivo
      virus infection and replication. Persistent infection with FCoV in a cheetah
      population results in continued virus circulation and may lead to a quasispecies
      of virus variants.

PMID- 16579756
TI  - Evaluation of dysregulation of the receptor tyrosine kinases Kit, Flt3, and Met
      in histiocytic sarcomas of dogs.
AB  - OBJECTIVE: To evaluate canine histiocytic sarcoma cell lines and tumor samples
      for dysregulation of the Kit/stem-cell factor (SCF), Flt3/Flt3 ligand (Flt3L),
      and Met/hepatocyte growth factor (HGF) receptor tyrosine kinase signaling
      pathways, as these are known to contribute to the differentiation and survival of
      normal dendritic cells as well as malignant transformation of dendritic cells in
      mouse models. SAMPLE POPULATION: 4 histiocytic sarcoma tumor cell lines and 35
      formalin-fixed histiocytic sarcoma specimens obtained from dogs. PROCEDURE:
      Histiocytic sarcoma cell lines were evaluated for expression of Kit/SCF,
      Flt3/Flt3L, and Met/HGF by use of reverse transcriptase-PCR procedures.
      Histiocytic sarcoma cell lines and tumor samples were evaluated for mutations in
      Kit, Flt3, and Met by use of PCR analysis of genomic DNA, followed by both
      sequencing and fluorescent PAGE for deletions or internal tandem duplications.
      The ability of the multi-targeted split-kinase inhibitor SU11654 to block
      proliferation and induce apoptosis of histiocytic sarcoma cell lines was also
      evaluated. RESULTS: No mutations in Kit, Flt3, and Met were identified in any of
      the cell lines or tumor samples evaluated. Furthermore, SU11654 did not induce
      cell-cycle arrest or apoptosis of histiocytic sarcoma lines, even at
      supratherapeutic doses. CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest
      that dysregulation of Kit/SCF, Flt3/Flt3L, and Met/HGF signaling pathways is
      unlikely to occur in histiocytic sarcomas of dogs and that inhibitors of the Kit,
      Flt3, and Met pathways are unlikely to provide clinical benefit to dogs with
      histiocytic sarcomas.

PMID- 16579757
TI  - Endotoxin-neutralizing activity of polymyxin B in blood after IV administration
      in horses.
AB  - OBJECTIVES: To measure serum polymyxin B concentration after single and repeated
      IV infusions in horses. ANIMALS: 5 healthy horses. PROCEDURES: In study 1, 1 mg
      (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24
      hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5
      treatments and blood samples were collected until 24 hours after the last dose.
      Polymyxin B concentration was measured as the ability to suppress nitrite
      production by murine macrophages stimulated with lipopolysaccharide and
      interferon-alpha. Urine was collected prior to the first drug infusion and 24
      hours after the fifth drug infusion for determination of urinary gamma-glutamyl
      transferase (GGT)-to-creatinine ratios. RESULTS: In study 1, mean +/- SEM maximal
      serum polymyxin B concentration was 2.93 +/- 0.38 microg/mL. Polymyxin B was
      undetectable 18 hours after infusion. In study 2, maximal polymyxin B
      concentrations after the first and fifth doses were 2.98 +/- 0.81 microg/mL and
      1.91 +/- 0.50 microg/mL, respectively. Mean trough concentration for all doses
      was 0.22 +/- 0.01 microg/mL. A significant effect of repeated administration on
      peak and trough serum concentration was not detected. Urine GGT-to-creatinine
      ratios were not affected by polymyxin B administration. CONCLUSIONS AND CLINICAL
      RELEVANCE: Polymyxin B given as multiple infusions to healthy horses by use of
      this protocol did not accumulate in the vascular compartment and appeared safe.
      Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as
      treatment for endotoxemia.

PMID- 16579758
TI  - Pharmacokinetics of amoxicillin administered in drinking water to recently weaned
      3- to 4-week-old pigs with diarrhea experimentally induced by Escherichia coli
      O149:F4.
AB  - OBJECTIVE: To measure effects of Escherichia coli O149:F4-induced diarrhea on
      water consumption and pharmacokinetics of amoxicillin after administration in
      drinking water. ANIMALS: 24 recently weaned 24- to 28-day-old crossbred pigs.
      PROCEDURE: 10 pigs were inoculated with E. coli O149:F4; all 10 pigs subsequently
      developed diarrhea. Pigs were medicated by administration of amoxicillin in the
      drinking water (0.75 mg/mL) for a 4-hour period on 2 consecutive days. Fourteen
      age-matched noninfected healthy pigs (control group) were medicated in a similar
      manner. Blood samples were obtained from both groups daily, and plasma
      concentrations of amoxicillin were analyzed by use of high-performance liquid
      chromatography. RESULTS: Diarrhea reduced the area under the plasma concentration
      versus-time curve (AUC) and maximum plasma concentration (C(max)) of amoxicillin
      on the first day of medication by 56% and 63%, respectively. The AUC of
      amoxicillin on the second day of medication for diarrheic pigs did not differ
      significantly from that of control pigs on the first day of medication.
      CONCLUSIONS AND CLINICAL RELEVANCE: E. coli-induced diarrhea reduced the AUC of
      amoxicillin and time that plasma concentration of amoxicillin was > 0.025
      microg/mL and, hence, less likely to have a therapeutic effect on the first day
      of administration in drinking water. On the assumption that plasma concentrations
      may indirectly reflect concentrations at the site of infection, analysis of our
      results suggests that higher doses of amoxicillin may be appropriate for
      administration in drinking water during a 4-hour period on the first day that
      pigs have diarrhea attributable to E. coli O149:F4.

PMID- 16579760
TI  - Evaluation of changes in antimicrobial susceptibility patterns of Pasteurella
      multocida subsp multocida isolates from pigs in Spain in 1987-1988 and 2003-2004.
AB  - OBJECTIVE: To determine the susceptibility of strains of Pasteurella multocida
      subsp multocida isolated from lung specimens of pigs with pneumonia to 20
      antimicrobials and to evaluate the emergence of resistance to those
      antimicrobials in Spain during the past 2 decades. SAMPLE POPULATION: 63 isolates
      recovered from 1987 to 1988 and 132 isolates recovered from 2003 to 2004.
      PROCEDURE: A broth microdilution method was used to determine minimal inhibitory
      concentration (MIC) range and values for MIC50 and MIC90. Resistance of a strain
      to an antimicrobial agent was determined by use of the breakpoint value when
      available. RESULTS: Isolates were generally susceptible to penicillin,
      ampicillin, ceftiofur, gentamicin, apramycin, neomycin, spectinomycin,
      chlortetracycline, erythromycin, tilmicosin, enrofloxacin, and florfenicol, and
      most isolates were resistant to clindamycin, tylosin tartrate, and tiamulin
      regardless of the time period. A substantial increase in resistance to sulfa
      chlorpiridazine, sulfadimethoxine, sulfathiazole, and trimethoprim
      sulfamethoxazole was observed, and a minor increase in resistance to
      oxytetracycline was also detected. Several multiresistance patterns were
      observed, most frequently among isolates recovered in the 2003 to 2004 interval.
      CONCLUSIONS AND CLINICAL RELEVANCE: Ceftiofur, florfenicol, and enrofloxacin are
      recommended for treatment of infections caused by P multocida subsp multocida in
      Spain. Increased frequency of resistance to oxytetracycline and sulfonamide drugs
      may be a contraindication for their use.

PMID- 16579759
TI  - Pharmacokinetics of methylprednisolone acetate after intra-articular
      administration and its effect on endogenous hydrocortisone and cortisone
      secretion in horses.
AB  - OBJECTIVE: To determine the pharmacokinetics of methylprednisolone (MP) and
      develop a pharmacokinetic-pharmacodynamic model of the related changes in plasma
      concentrations of endogenous hydrocortisone (HYD) and cortisone (COR) following
      intra-articular administration of methylprednisolone acetate (MPA) in horses.
      ANIMALS: 6 Thoroughbreds. PROCEDURES: In each horse, 200 mg of MPA was injected
      intrasynovially into a carpal joint, and plasma MP, HYD, and COR concentrations
      were determined via liquid chromatography-mass spectrometry. RESULTS: A 5
      compartment pharmacokinetic-pharmacodynamic model was used to describe the
      concatenated changes in the plasma concentrations of MP, HYD, and COR and to
      estimate the instantaneous rate of endogenous HYD production. The median transfer
      half-life (t(1/2t)) of methylprednisolone from the joint to plasma and
      elimination half-life (t(1/2e)) from plasma were 1.7 and 19.2 hours,
      respectively. Maximum plasma concentration of methylprednisolone was 7.26 +/- 3.3
      ng/mL at 8 hours, which decreased to 0.11 +/- 0.08 ng/mL at 144 hours after
      injection. At 3 hours after MPA administration, plasma COR and HYD concentrations
      were significantly decreased from baseline values (from 2.9 +/- 0.28 ng/mL to
      2.10 +/- 1.0 ng/mL and from 61.1 +/- 18.9 ng/mL to 25.7 +/- 12.1 ng/mL,
      respectively). CONCLUSIONS AND CLINICAL RELEVANCE: The sensitivity of the
      analytic method used allowed complete description of the related kinetics of MP,
      HYD, and COR following intra-articular administration of MPA. A single intra
      articular administration of MPA profoundly affected the secretion of HYD and COR
      in horses; secretion of endogenous corticosteroids remained suppressed for as
      long as 240 hours after injection.

PMID- 16579761
TI  - Time-dependent alterations in gene expression of interleukin-8 in the bronchial
      epithelium of horses with recurrent airway obstruction.
AB  - OBJECTIVE: To evaluate time-dependent alterations in gene expression of
      chemokines in bronchial epithelium of recurrent airway obstruction (RAO)-affected
      horses and whether alterations resulted from increases in gene expression of
      interleukin (IL)-17 in cells isolated from bronchoalveolar lavage fluid (BALF).
      ANIMALS: 8 RAO-susceptible horses and 9 control horses. PROCEDURE: In 2
      experiments, both groups of horses were evaluated after being maintained on
      pasture and after being stabled and fed dusty hay for 1, 14, 35, and 49 days
      (experiment 1) or 14 and 28 days (experiment 2). In experiment 1, gene expression
      of IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1), granulocyte-macrophage colony
      stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and
      Toll-like receptor 4 (TLR4) in epithelium and IL-8, IL-17, and TLR4 in BALF cells
      was measured. In experiment 2, bronchial biopsy specimens were evaluated for IL-8
      immunoreactivity. RESULTS: In RAO-susceptible horses after 14 days of challenge
      exposure, there was a 3- and 10-fold increase in gene expression of IL-8 for
      epithelial and BALF cells and an increase in IL-8 immunoreactivity in epithelial
      cells. Challenge exposure failed to alter gene expression of CXCL1, GM-CSF, G
      CSF, and TLR4 in epithelial cells of any horses at any time point. During
      challenge exposure, gene expression of BALF cell IL-17 was downregulated in
      control horses (day 1) and upregulated in RAO-affected horses (day 35).
      CONCLUSIONS AND CLINICAL RELEVANCE: Epithelial-derived IL-8 may promote airway
      neutrophilia, but the inciting stimulus is unlikely to be IL-17 because
      upregulation of this gene is subsequent to that of IL-8 in epithelial cells.

PMID- 16579762
TI  - In vitro mechanical evaluation of torsional loading in simulated canine tibiae
      for a novel hourglass-shaped interlocking nail with a self-tapping tapered
      locking design.
AB  - OBJECTIVE: To describe a novel interlocking nail (ILN) and locking system and
      compare the torsional properties of constructs implanted with the novel ILN or a
      standard 8-mm ILN (ILN8) by use of a gap-fracture model. SAMPLE POPULATION: 8
      synthetic specimens modeled from canine tibiae. PROCEDURES: An hourglass-shaped
      ILN featuring a tapered locking mechanism was designed. A synthetic bone model
      was custom-made to represent canine tibiae with a 50-mm comminuted diaphyseal
      fracture. Specimens were repaired by use of a novel ILN or an ILN8 with screws.
      Specimens were loaded for torsional measurements. Construct compliance and
      angular deformation were compared. RESULTS: Compliance of the ILN8 was
      significantly smaller than that of the novel ILN. Mean +/- SD maximum angular
      deformation of the ILN8 construct (23.12 +/- 0.65 degrees) was significantly
      greater, compared with that of the novel ILN construct (9.45 +/- 0.22 degrees).
      Mean construct slack for the ILN8 group was 15.15 +/- 0.63 degrees, whereas no
      slack was detected for the novel ILN construct. Mean angular deformation for the
      ILN8 construct once slack was overcome was significantly less, compared with that
      of the novel ILN construct. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of
      results of this study suggests that engineering of the locking mechanism enabled
      the novel hourglass-shaped ILN system to eliminate torsional instability
      associated with the use of current ILNs. Considering the potential deleterious
      effect of torsional deformation on bone healing, the novel ILN may represent a
      biomechanically more effective fixation method, compared with current ILNs, for
      the treatment of comminuted diaphyseal fractures.

PMID- 16579764
TI  - In vitro evaluation of five canine tibial plateau leveling methods.
AB  - OBJECTIVE: To compare application time, accuracy of tibial plateau slope (TPS)
      correction, presence and magnitude of rotational and angular deformities, and
      mechanical properties of 5 canine tibial plateau leveling methods. SAMPLE
      POPULATION: 27 canine tibial replicas created by rapid prototyping methods.
      PROCEDURE: The application time, accuracy of TPS correction, presence and
      magnitude of rotational and angular deformation, and construct axial stiffness of
      3 internal fixation methods (tibial plateau leveling osteotomy, tibial wedge
      osteotomy, and chevron wedge osteotomy [CWO]) and 2 external skeletal fixation
      (ESF) methods (hinged hybrid circular external fixation and wedge osteotomy
      linear fixation [WOLF]) were assessed. RESULTS: Mean bone model axial stiffness
      did not differ among methods. Mean application time was more rapid for WOLF than
      for other methods. Mean TPSs did not differ from our 5 degrees target and were
      lower for ESF methods, compared with internal fixation methods. Mean
      postoperative rotational malalignment did not differ from our target or among
      groups. Mean postoperative medio-lateral angulation did not differ from our
      target, except for CWO. Internal fixation methods lead to axially stiffer
      constructs than ESF methods. Reuse of ESF frames did not lead to a decrease in
      axial stiffness. CONCLUSIONS AND CLINICAL RELEVANCE: The 5 tibial plateau
      leveling methods had acceptable geometric and mechanical properties. External
      skeletal fixation methods were more accurate as a result of precise data
      available for determining the exact magnitude of correction required to achieve a
      5 degrees TPS.

PMID- 16579763
TI  - Biomechanical and histologic comparison of single-layer continuous Cushing and
      simple continuous appositional cystotomy closure by use of poliglecaprone 25 in
      rats with experimentally induced inflammation of the urinary bladder.
AB  - OBJECTIVE: To biomechanically and histologically compare single-layer continuous
      Cushing and simple continuous appositional cystotomy closure in rats with xylene
      induced cystitis. ANIMALS: 40 female Sprague-Dawley rats. PROCEDURE: Rats were
      anesthetized, their urinary bladders catheterized and evacuated, and xylene
      instilled in each bladder for 5 minutes and then aspirated. Forty-eight hours
      later, ventral midline celiotomy and cystotomy (8 mm) were performed. Cystotomies
      were closed with 6-0 poliglecaprone 25 by use of a single-layer continuous
      Cushing or simple continuous appositional pattern (20 rats/group), and cystotomy
      times were recorded. Rats were allocated to healing durations (5 rats/group) of
      0, 3, 7, and 14 days. Celiotomies were closed in a routine manner. After the
      allotted healing interval, another celiotomy was performed, the urethra
      cannulated, and ureters ligated. The cannula was secured to the urethra, and the
      bladder infused at 0.1 mL/min. Leak pressure volume, leak pressure, peak pressure
      volume, and peak pressure were recorded via a pressure transducer. Bladders were
      harvested and histologically assessed. RESULTS: Cystotomy time, biomechanical
      testing values, and overall inflammation scores did not differ between closure
      methods for any healing duration. Both methods had significantly greater leak
      pressures, with the appositional method also having significantly greater peak
      pressures on day 7, compared to day 0. Biomechanical testing values decreased
      from day 7 to 14 as a result of juxtaincisional weakening of the bladder and
      xylene-induced changes in collagen. CONCLUSIONS AND CLINICAL RELEVANCE: Simple
      continuous appositional was equal biomechanically and histologically to
      continuous Cushing for all comparison variables. Poliglecaprone 25 was acceptable
      for cystotomy closure.

PMID- 16579765
TI  - Detection of superoxide anion generation by equine spermatozoa.
AB  - OBJECTIVE: To identify the generation of the superoxide anion by equine
      spermatozoa. SAMPLE POPULATION: Multiple ejaculates collected from 3 Thoroughbred
      stallions. PROCEDURES: Induced superoxide production by reduced nicotinamide
      adenine dinucleotides (NAD[P]H; ie, reduced nicotinamide adenine dinucleotide
      [NADH] and reduced nicotinamide adenine dinucleotide phosphate [NADPH]) was
      measured by use of a nitroblue tetrazolium (NBT) reduction assay on whole
      spermatozoa and a cytochrome c reduction assay on isolated membrane fractions of
      spermatozoa. Localization of superoxide generation was determined by use of NBT
      cytochemistry. RESULTS: A dose-dependent increase in NBT reduction was found in
      the presence of NADPH, which was inhibited by superoxide dismutase (SOD). The
      flavoprotein inhibitor, diphenyleneiodonium (DPI; 5 or 15 microM), significantly
      decreased NBT reduction. Cytochrome c reduction by plasma membranes of
      spermatozoa was significantly higher in the presence of NADPH than in its
      absence. Cytochemical staining of equine spermatozoa in the presence of NADPH and
      NADH revealed diaphorase labeling in the spermatozoon midpiece and head. This
      staining was inhibited by DPI and SOD. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results of our study indicate that superoxide generation is associated with a
      membrane-associated NAD(P)H oxidase present in equine spermatozoa, although
      mitochondrial generation of superoxide is also detected. This oxidase may play a
      role in cell signaling or may also contribute to cytopathic effects associated
      with oxidative stress in equine spermatozoa.

PMID- 16579766
TI  - Effects of ergotamine and ergovaline on the electromyographic activity of smooth
      muscle of the reticulum and rumen of sheep.
AB  - OBJECTIVE: To investigate the effects of IV administration of ergotamine and
      ergovaline and intraruminal administration of ergotamine on electromyographic
      (EMG) activity of reticuloruminal smooth muscle in conscious sheep. ANIMALS: 3
      sheep with indwelling electrodes in the musculature of the reticulum and rumen.
      PROCEDURE: In a crossover design study, reticuloruminal motility before and after
      IV administration of ergotamine (5, 10, 20, and 40 nmol/kg) or ergovaline (2.5,
      5, and 10 nmol/kg) was evaluated; EMG effects were compared with those of
      corresponding control treatments (IV administration of saline [0.9% NaCl]
      solution or acetone, respectively) in sheep. Ergotamine (800 nmol/kg) or water
      was also administered intraruminally and their effects compared. RESULTS: After
      IV administration of ergopeptides, vagally dependent cyclical A and B sequences
      of contraction of the reticulorumen were immediately inhibited, preceding
      increases in baseline EMG activity (tonus). The return of cyclical contractions
      was associated with an increase in contraction amplitude. The effects were dose
      dependent; administration of 40 nmol of ergotamine/kg resulted in responses that
      continued for 3 to 4 hours. The effects of intraruminal administration of
      ergotamine were variable; after 8 hours, EMG activity was increased from baseline
      for < 2 hours in 1 sheep, 10 hours in another, and > 15 hours in the third.
      CONCLUSIONS AND CLINICAL RELEVANCE: In sheep, the effects of ergotamine and
      ergovaline on reticuloruminal motility after IV administration and the duration
      of responses following intraruminal administration suggest that disruption of
      digestion may occur in animals grazing endophyte-infected pasture that has a high
      ergopeptide content.

PMID- 16579767
TI  - Effects of administration of fluids and diuretics on glomerular filtration rate,
      renal blood flow, and urine output in healthy awake cats.
AB  - OBJECTIVES: To determine effects of commonly used diuretic treatments on
      glomerular filtration rate (GFR), renal blood flow (RBF), and urine output (UO)
      and compare 2 methods of GFR measurement in healthy awake cats. ANIMALS: 8
      healthy cats. PROCEDURE: In a randomized crossover design, cats were randomly
      allocated to 4 groups: control; IV administration of fluids; IV administration of
      fluids and mannitol; and IV administration of fluids, dopamine, and furosemide.
      Inulin and para-aminohippuric acid were used for determination of plasma
      clearance for GFR and RBF, respectively. Plasma clearance of technetium-Tc-99m
      diethylenetriaminepentacetic acid (99mTc-DTPA) was also used for GFR
      determination. RESULTS: Furosemide-dopamine induced the largest UO, compared with
      other groups. Both mannitol and fluid therapy increased RBF, compared with the
      control group. Mannitol, and not fluid therapy, increased RBF, compared with
      furosemide-dopamine. There were significant differences in GFR values calculated
      from 99mTc-DTPA and inulin clearances between the 2 groups. In all groups, use of
      99mTc-DTPA caused underestimation of GFR, compared with use of inulin.
      CONCLUSIONS AND CLINICAL RELEVANCE: In healthy awake cats, administration of
      furosemide-dopamine did not increase GFR or RBF despite increased UO. Fluid
      therapy and fluid therapy plus mannitol improved RBF. Determination of GFR by use
      of 99mTc-DTPA cannot always be substituted for inulin clearance when accurate
      measurement is required.

PMID- 16579768
TI  - Evaluation of the urodynamic and hemodynamic effects of orally administered
      phenylpropanolamine and ephedrine in female dogs.
AB  - OBJECTIVE: To compare the urodynamic and hemodynamic effects of different dosages
      of phenylpropanolamine and ephedrine and determine effective dosages in
      increasing urethral resistance in female dogs. ANIMALS: 20 sexually intact female
      Beagles. PROCEDURE: Dogs were allocated into 4 groups and received
      phenylpropanolamine once, twice, or 3 times daily, or ephedrine twice daily, for
      14 days. On days 0, 7, and 14, urethral pressure profiles were performed while
      dogs were anesthetized with propofol. Variables recorded included maximum
      urethral pressure, maximum urethral closure pressure, integrated pressure,
      functional profile length, anatomic profile length, plateau distance, distance
      before maximum urethral pressure, and maximum meatus pressure. Arterial and
      central venous pressures were measured before anesthetic induction and 10 and 35
      minutes after induction. RESULTS: Administration of phenylpropanolamine once
      daily or ephedrine twice daily significantly increased maximum urethral pressure
      and maximum urethral closure pressure. Values for integrated pressure were
      significantly increased after 14 days of once-daily administration of
      phenylpropanolamine. Variables did not change significantly from day 7 to day 14.
      Diastolic and mean arterial blood pressures increased significantly during the
      treatment periods, and arterial pressure decreased during propofol infusion.
      CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of phenylpropanolamine
      once daily or ephedrine twice daily increased urethral resistance in clinically
      normal dogs and may be recommended for management of urethral sphincter mechanism
      incompetence. Treatment efficacy may be assessed after 1 week. Dogs with
      concurrent cardiovascular disease should be monitored for blood pressure while
      receiving alpha-adrenergic agents because of the effects on diastolic and mean
      arterial pressure.

PMID- 16579769
TI  - Evaluation of the effects of stress in cats with idiopathic cystitis.
AB  - OBJECTIVE: To determine the effects of stress in cats with feline idiopathic
      cystitis (FIC) by evaluating bladder permeability, sympathetic nervous system
      function, and urine cortisol:creatinine (C:Cr) ratios during periods of stress
      and after environmental enrichment. DESIGN: Prospective study. ANIMALS: 13 cats
      with FIC and 12 healthy cats. PROCEDURE: Cats subjected to an acute-onset
      moderate stressor for 8 days received IV injections of fluorescein. Serum
      fluorescein concentrations were determined and compared with those of controls to
      evaluate bladder permeability, and urine C:Cr ratios were compared to evaluate
      function of the hypothalamic-pituitary-adrenal (HPA) axis. Plasma catecholamine
      concentrations were analyzed in a subset of cats. After 8 days of moderate
      stress, cats were moved to an enriched environment, and tests were repeated after
      21 days. RESULTS: Serum fluorescein concentrations were significantly higher in
      cats with FIC at all time points. In the cats in which plasma catecholamine
      concentrations were determined, concentrations of dihydroxyphenylalanine,
      norepinephrine, and dihyroxyphenylglycol were significantly higher in cats with
      FIC at all time points, whereas no differences in urine C:Cr ratio between groups
      were observed. CONCLUSION AND CLINICAL RELEVANCE: Cats with FIC appeared to have
      altered bladder permeability, most notably during the period of initial stress.
      The increase in plasma dihydroxyphenylalanine concentration suggests that there
      may be stress-induced increase in the activity of tyrosine hydroxylase, which
      catalyzes the rate-limiting step in catecholamine synthesis. In contrast, no
      effects of stress on C:Cr ratios were observed, which suggests there was
      dissociation between the sympathetic nervous system and HPA-axis responses to
      stress.

PMID- 16579771
TI  - CDC on the offensive to stamp out rodent virus.

PMID- 16579772
TI  - Views conclusions in ultrasound study as unsupported.

PMID- 16579773
TI  - Euthanasia and quality of life.

PMID- 16579774
TI  - What is your diagnosis? Spinal arachnoid cysts.

PMID- 16579775
TI  - What is your diagnosis? Fungal osteomyelitis.

PMID- 16579776
TI  - Diagnostic imaging in veterinary dental practice. Unerupted tooth resulting in a
      dentigerous cyst causing resorption of bone.

PMID- 16579777
TI  - ECG of the month. Transvenous pacing of the RVA.

PMID- 16579778
TI  - Toxicologic hazards for police dogs involved in drug detection.

PMID- 16579779
TI  - Effect of age on reference intervals of serum biochemical values in kittens.
AB  - OBJECTIVE: To determine the effect of age on reference intervals of serum
      biochemical values in kittens. DESIGN: Prospective clinical trial. ANIMALS: 55
      kittens from 12 specific-pathogen-free queens. PROCEDURE: Kittens were allocated
      at birth into colostrum-fed (n = 27) and colostrum-deprived (28) groups. Blood
      was collected at birth and on days 1, 2, 4, 7, 14, 28, and 56. Serum samples were
      analyzed for activities of alkaline phosphatase, alanine aminotransferase,
      aspartate aminotransferase, creatine kinase, lactate dehydrogenase, gamma
      glutamyltransferase, amylase, and lipase and for concentrations of albumin, total
      protein, bilirubin, urea nitrogen, creatinine, cholesterol, glucose, calcium,
      phosphorus, and triglycerides by use of an automated analyzer. Total serum solids
      concentrations were determined by use of refractometry. Serum IgG concentrations
      were quantified by use of radial immunodiffusion. RESULTS: For several analytes,
      reference intervals changed rapidly, most notably during the first few days of
      life. Reference intervals for alkaline phosphatase, creatine kinase, lactate
      dehydrogenase, and triglycerides were higher from birth to 8 weeks than adult
      reference intervals. Aspartate aminotransferase, bilirubin, urea nitrogen, and
      creatinine were higher than in adults at birth but were similar to or lower than
      adult reference intervals by 8 weeks. Compared with adult reference intervals,
      reference intervals for calcium and phosphorus concentrations were higher and for
      albumin and total protein concentrations were lower throughout the study period.
      CONCLUSIONS AND CLINICAL RELEVANCE: Important differences exist between reference
      intervals for serum biochemical values of neonatal and adult cats. Age
      appropriate reference intervals should be used for accurate assessment of serum
      biochemical test results in cats.

PMID- 16579782
TI  - Effect of transdermally administered fentanyl on minimum alveolar concentration
      of isoflurane in normothermic and hypothermic dogs.
AB  - OBJECTIVE: To determine whether the minimum alveolar concentration (MAC) of
      isoflurane was altered by transdermal administration of fentanyl in normothermic
      and hypothermic dogs. DESIGN: Randomized complete block crossover design.
      ANIMALS: 6 mature healthy dogs. PROCEDURE: Dogs received each of 4 treatments in
      random order. Following induction of anesthesia, normothermia was maintained in
      dogs that were treated with a fentanyl patch (F-NORM) or sham patch (C-NORM), or
      hypothermia was maintained in dogs that were treated with a fentanyl patch (F
      HYPO) or sham patch (C-HYPO). The appropriate patch was applied 24 hours prior to
      induction of anesthesia. Anesthesia was induced with isoflurane in oxygen; the
      dogs were intubated and mechanically ventilated. Target esophageal temperatures
      were maintained within 1 degrees C of baseline values (normothermia) or at 34.5
      degrees C (94.1 degrees F; hypothermia) for 1 hour prior to starting MAC
      determinations. Supramaximal stimulation was achieved with an electrical
      stimulator attached to needle electrodes placed in the buccal mucosa of the lower
      jaw of the dog. RESULTS: Mean MAC +/- SEM of isoflurane during C-NORM, C-HYPO, F
      NORM, and F-HYPO treatments were 1.20 +/- 0.17, 0.89 +/- 0.18, 0.76 +/- 0.10, and
      0.81 +/- 0.17, respectively. The mean MAC during C-NORM was significantly higher
      than values for the other treatments. There was no significant difference in mean
      MAC among the C-HYPO, F-NORM, and F-HYPO treatments. CONCLUSIONS AND CLINICAL
      RELEVANCE: Data suggest that transdermal administration of fentanyl significantly
      reduces isoflurane requirements in normothermic dogs. The isoflurane MAC-sparing
      effects of transdermal fentanyl are not apparent in hypothermic dogs.

PMID- 16579781
TI  - Evaluation of surrogate markers for passive transfer of immunity in kittens.
AB  - OBJECTIVE: To identify surrogate markers of passive transfer of immunity in
      kittens. DESIGN: Prospective clinical trial. ANIMALS: 55 kittens from 12 specific
      pathogen-free queens. PROCEDURE: Kittens were allocated at birth into colostrum
      fed (n = 27) and colostrum-deprived (28) groups. Blood was collected at birth and
      on days 1, 2, 4, 7, 14, 28, and 56. Serum samples were analyzed for activities of
      alkaline phosphatase (ALP), alanine aminotransferase, aspartate aminotransferase,
      creatine kinase, lactate dehydrogenase, gamma-glutamyltransferase, amylase, and
      lipase and for concentrations of albumin, total protein, bilirubin, urea
      nitrogen, creatinine, cholesterol, glucose, calcium, phosphorus, and
      triglycerides by use of an automated analyzer. Total serum solids concentrations
      were estimated by use of refractometry. Serum IgG concentrations were quantified
      by use of radial immunodiffusion. RESULTS: All kittens were agammaglobulinemic at
      birth. Colostrum-fed kittens had significantly higher IgG concentrations than did
      colostrum-deprived kittens from 1 though 28 days of age. Transient significant
      differences in serum biochemical variables between the colostrum-deprived and
      colostrum-fed groups were substantially resolved by day 4. Passive transfer of
      immunity could be reliably determined at 1 day of age and to a lesser extent at 2
      days of age only by measurement of serum activity of ALP. CONCLUSIONS AND
      CLINICAL RELEVANCE: Adequacy of passive transfer in kittens initially correlated
      with serum activity of ALP, but quantification of serum IgG concentration was
      necessary after 2 days of age.

PMID- 16579783
TI  - Use of internal splinting to realign a noncompliant sternum in a cat with pectus
      excavatum.
AB  - CASE DESCRIPTION: A 5.5-month-old female domestic longhair cat was examined
      because of dorsal deviation of the caudal aspect of the sternum and progressively
      worsening dyspnea during play activities. CLINICAL FINDINGS: A diagnosis of
      pectus excavatum was made clinically and confirmed radiographically. The cardiac
      silhouette was shifted into the right hemithorax. The vertebral index (VI) and
      frontosagittal index (FSI), which are radiographic indices used to grade the
      extent of the deformity, were 5.2 and 3.0, respectively. Minimum thoracic height
      was 13 mm at this time. TREATMENT AND OUTCOME: The sternal malposition was
      corrected during surgery; for stabilization, an internal splint was provided by
      use of a plate that was applied to the ventral side of the sternum. Radiographic
      indices improved until day 85; at that time, an increase in the distance between
      plate and sternum was detected, and plate removal was advised. The radiographic
      indices improved again after plate removal. At 310 days after surgery, VI was
      9.6, FSI was 1.6, and minimum thoracic height was 34 mm. No dyspnea was evident
      during physical examination. CLINICAL RELEVANCE: Results of treatment suggest
      that this technique may be useful as an alternative surgical option for cats with
      pectus excavatum that have a noncompliant sternum.

PMID- 16579784
TI  - Association of argyrophilic nucleolar organizing regions, Ki-67, and
      proliferating cell nuclear antigen scores with histologic grade and survival in
      dogs with soft tissue sarcomas: 60 cases (1996-2002).
AB  - OBJECTIVE: To determine whether argyrophilic nucleolar organizing regions
      (AgNORs), Ki-67, and proliferating cell nuclear antigen (PCNA) scores were
      associated with histologic grade and survival in dogs with soft tissue sarcomas
      (STSs). DESIGN: Retrospective study. ANIMALS: 60 dogs with STSs. PROCEDURE:
      Medical records were examined and histologic specimens were reviewed. Tissue
      specimens obtained from archival materials were used to prepare sections for
      histologic staining for AgNOR and immunohistochemical staining for Ki-67 and PCNA
      labeling. Follow-up monitoring was obtained by reevaluation or telephone
      conversations with referring veterinarians or owners. RESULTS: 27 (45%) STSs were
      grade 1, 23 (38%) were grade 2, and 10 (17%) were grade 3. The mean and median
      AgNOR, Ki-67, and PCNA scores were determined, and significant positive
      associations among AgNOR and Ki-67 scores with histologic grade and mitotic score
      were detected. Fifty-four dogs had adequate follow-up examinations and were
      included in survival analysis and evaluation of prognostic factors. Overall
      median survival time was > 1,306 days. Twelve of 54 (22%) dogs died of tumor
      related causes. Metastatic disease developed in 8 of 54 (15%) dogs. Results of
      univariate analysis indicated that increased mitotic score, increased AgNOR
      score, increased Ki-67 score, incomplete surgical margins, noncurative intent
      surgery, Ki-67 score greater than the median Ki-67 score, and AgNOR score greater
      than the median AgNOR score were prognostic factors for decreased survival time.
      Results of multivariate analysis indicated that increased AgNOR score was the
      only prognostic factor for decreased survival time. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that AgNORs and possibly Ki-67 should be routinely
      evaluated with histologic grading for STSs in dogs.

PMID- 16579786
TI  - Evaluation of the effects of footwear hygiene protocols on nonspecific bacterial
      contamination of floor surfaces in an equine hospital.
AB  - OBJECTIVE: To evaluate the effects of footwear hygiene protocols on bacterial
      contamination of floor surfaces in an equine hospital. DESIGN: Field trial.
      PROCEDURES: Footwear hygiene protocols evaluated included use of rubber overboots
      with footbaths and footmats containing a quaternary ammonium disinfectant, rubber
      overboots with footbaths and footmats containing a peroxygen disinfectant, and no
      restrictions on footwear type but mandatory use of footbaths and footmats
      containing a peroxygen disinfectant. Nonspecific aerobic bacterial counts were
      determined via 2 procedures for sample collection and bacterial enumeration
      (contact plates vs swabbing combined with use of spread plates), and the effects
      of each footwear hygiene protocol were compared. RESULTS: There were no
      consistent findings suggesting that any of the protocols were associated with
      differences in numbers of bacteria recovered from floor surfaces. Although there
      were detectable differences in numbers of bacteria recovered in association with
      different footwear hygiene protocols, differences in least square mean bacterial
      counts did not appear to be clinically relevant (ie, were < 1 log10). CONCLUSIONS
      AND CLINICAL RELEVANCE: Although cleaning and disinfection of footwear are
      important aids in reducing the risk of nosocomial transmission of infectious
      agents in veterinary hospitals, the numbers of aerobic bacteria recovered from
      floor surfaces were not affected by use of rubber overboots or the types of
      disinfectant used in this study. Further study is warranted to evaluate the
      usefulness of footwear hygiene practices relative to their efficacy for reducing
      transmission of specific pathogens or decreasing nosocomial disease risk.

PMID- 16579785
TI  - Clinical signs and clinicopathologic abnormalities in dogs with clinical
      spirocercosis: 39 cases (1996-2004).
AB  - OBJECTIVE: To determine clinical signs and clinicopathologic abnormalities in
      dogs with naturally occurring clinical spirocercosis. DESIGN: Retrospective case
      series. ANIMALS: 39 dogs with spirocercosis. PROCEDURES: Medical records were
      reviewed, and information on signalment, residence (rural vs urban), owner
      complaints, physical examination findings, clinicopathologic abnormalities,
      radiographic and endoscopic findings, and concurrent systemic diseases was
      recorded. RESULTS: Hellenic hounds and mixed-breed dogs were overrepresented,
      compared with a group of 117 control dogs without spirocercosis that were
      examined because of gastrointestinal tract disease, and mean body weight of dogs
      with spirocercosis was significantly higher than mean body weight of control
      dogs. Odynophagia (34 [87%]), regurgitation (24 [62%]), and excessive salivation
      (14 [36%]) were the most common clinical findings. The most common radiographic
      abnormalities were a mass in the caudodorsal aspect of the mediastinum (15/35
      [43%]) and spondylitis of the caudal thoracic vertebrae (10 [29%]). Parasitic
      nodules were seen during esophagoscopy in all 39 dogs. Normocytic, normochromic,
      nonregenerative anemia; neutrophilic leukocytosis; hyperproteinemia; and high
      alkaline phosphatase activity were significantly more common in dogs with
      spirocercosis than in a control group of 56 healthy dogs. Concurrent systemic
      diseases, mainly leishmaniosis, dirofilariosis, and monocytic ehrlichiosis, were
      documented in 14 (36%) dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that clinical spirocercosis occurs more often in young-adult, large-breed dogs.
      Nonregenerative anemia, neutrophilic leukocytosis, hyperproteinemia, and high
      alkaline phosphatase activity may be useful clinicopathologic indicators of this
      disease.

PMID- 16579787
TI  - Evaluation of antimicrobial susceptibility patterns in Campylobacter spp isolated
      from dairy cattle and farms managed organically and conventionally in the
      midwestern and northeastern United States.
AB  - OBJECTIVE: To describe antimicrobial susceptibility patterns in Campylobacter spp
      isolated from dairy cattle and farms managed organically and conventionally in
      the midwestern and northeastern United States. DESIGN: Longitudinal study. SAMPLE
      POPULATION: 128 farms. PROCEDURE: Samples and data were collected every 2 months
      from August 2000 to October 2001. Fecal samples were collected from calves and
      cows. Milk samples were obtained from the bulk tank and milk line filters.
      Environmental samples were obtained from a water source, feed bunks of lactating
      cows, and cattle housing areas. Campylobacter identification and antimicrobial
      susceptibility testing were performed at a central laboratory by use of
      microbroth dilution with 2 customized antimicrobial susceptibility panels.
      RESULTS: 460 and 1,570 Campylobacter isolates were obtained from organic and
      conventional dairy farms, respectively. Most isolates from both farm types were
      susceptible to most antimicrobial agents tested, and antimicrobial susceptibility
      of conventional dairy isolates was decreased, compared with organic dairy
      isolates. Low proportions of isolates resistant to ampicillin (< 10%) and
      moderate proportions resistant (30% to 60%) to kanamycin, sulfamethoxazole, and
      tetracycline were observed on both farm types. The proportion of isolates
      resistant to tetracycline was higher for conventional than organic farms.
      CONCLUSIONS AND CLINICAL RELEVANCE: Campylobacter isolates from dairy cattle and
      farms managed organically and conventionally had similar patterns of
      antimicrobial resistance; the proportion of resistant isolates was higher for
      conventional than organic farms.

PMID- 16579789
TI  - Immunologic responses and reproductive outcomes following exposure to wild-type
      or attenuated porcine reproductive and respiratory syndrome virus in swine under
      field conditions.
AB  - OBJECTIVE: To compare immunologic responses and reproductive outcomes in sows
      housed under field conditions following controlled exposure to a wild-type strain
      of porcine reproductive and respiratory syndrome virus (PRRSV strain WTV) or
      vaccination with a modified-live virus (MLV) vaccine. DESIGN: Randomized
      controlled trial. ANIMALS: 30 PRRSV-naive 10-week-old female pigs. PROCEDURE:
      Humoral and cell-mediated immune responses were monitored while pigs were held in
      isolation for 84 days after inoculation with the WTV strain (n = 10), inoculation
      with the WTV strain and 42 days later vaccination with a killed-virus vaccine
      (10), or vaccination with an MLV vaccine (10). Reproductive outcomes were
      measured after pigs were released into the farm herd. RESULTS: Inoculation with
      the WTV strain, regardless of whether a killed-virus vaccine was subsequently
      administered, elicited faster and more substantial production of strain-specific
      neutralizing antibodies, as well as a more rapid generation of interferon-gamma
      secreting cells, than did vaccination with the MLV vaccine. Despite the enhanced
      immune responses in pigs inoculated with the WTV strain, animals vaccinated with
      the MLV vaccine produced a mean of 2.45 more pigs than did sows exposed to the
      WTV strain, mainly because of a lower rate for failure to conceive. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results suggest that current assays of immunity to PRRSV
      correlate only imperfectly with degree of clinical protection and that the
      practice of controlled exposure of sows to a circulating PRRSV strain should be
      reconsidered in light of negative clinical outcomes.

PMID- 16579791
TI  - BMI: new aspects of a classical risk factor for hypertensive disorders in
      pregnancy.
AB  - HDP (hypertensive diseases in pregnancy) are one of the leading causes of
      maternal and fetal mortality and morbidity. BMI (body mass index) is an
      established risk factor for pre-eclampsia, but its role in HELLP syndrome is
      unknown. We therefore investigated BMI as a risk factor in the development of
      HELLP syndrome. At the beginning of pregnancy, BMI was measured in 1067 women
      with a history of HDP and 1063 controls. Diagnoses of HDP were classified
      according to ISSHP (International Society for the Study of Hypertension in
      Pregnancy) and BMI according to WHO (World Health Organization) criteria. After
      verification of exclusion criteria and matching for confounders, 687 women with
      hypertensive diseases in pregnancy and 601 controls remained for statistical
      evaluation by chi(2) test and multiple logistic regressions. As a continuous
      variable, the increase in BMI was associated with an increase in the development
      of gestational hypertension {OR (odds ratio), 1.1 [95% CI (confidence interval)
      1.062-1.197]} and pre-eclampsia [OR, 1.1 (95% CI, 1.055-1.144)]}, but not for
      HELLP syndrome. According to WHO definitions, overweight women (BMI > or =25 and
      <30 kg/m(2)) had a 2-fold (95% CI, 1.365-2.983) risk and obese women (BMI > or
      =30 kg/m(2)) had a 3.2-fold (95% CI, 1.7-5.909) risk of developing pre-eclampsia
      when compared with women of normal weight (BMI > or =15.5 and <25 kg/m(2)). Being
      overweight or having obesity had no effect on the risk of HELLP syndrome. As an
      increased BMI is correlated with the risk of developing pre-eclampsia but not
      HELLP syndrome, both diseases have a different risk profile. This finding
      supports that underlying physiological mechanisms in pre-eclampsia vary from
      those in HELLP syndrome.

PMID- 16579792
TI  - Destabilizing missense mutations in the tumour suppressor protein p53 enhance its
      ubiquitination in vitro and in vivo.
AB  - p53 ubiquitination catalysed by MDM2 (murine double minute clone 2 oncoprotein)
      provides a biochemical assay to dissect stages in E3-ubiquitin-ligase-catalysed
      ubiquitination of a conformationally flexible protein. A mutant form of p53
      (p53(F270A)) containing a mutation in the second MDM2-docking site in the DNA
      binding domain of p53 (F270A) is susceptible to modification of long-lived and
      high-molecular-mass covalent adducts in vivo. Mutant F270A is hyperubiquitinated
      in cells as defined by immunoprecipitation and immunoblotting with an anti
      ubiquitin antibody. Transfection of His-tagged ubiquitin along with p53(R175H) or
      p53(F270A) also results in selective hyperubiquitination in cells under
      conditions where wild-type p53 is refractory to covalent modification. The extent
      of mutant p53(R175H) or p53(F270A) unfolding in cells as defined by exposure of
      the DO-12 epitope correlates with the extent of hyperubiquitination, suggesting a
      link between substrate conformation and E3 ligase function. The p53(F270A:6KR)
      chimaeric mutant (where 6KR refers to the simultaneous mutation of lysine
      residues at positions 370, 372, 373, 381, 382 and 386 to arginine) maintains the
      high-molecular-mass covalent adducts and is modified in an MDM2-dependent manner.
      Using an in vitro ubiquitination system, mutant p53(F270A) and the p53(F270A:6KR)
      chimaeric mutant is also subject to hyperubiquitination outwith the C-terminal
      domain, indicating direct recognition of the mutant p53 conformation by (a)
      factor(s) in the cell-free ubiquitination system. These data identify an in vitro
      and in vivo assay with which to dissect how oligomeric protein conformational
      alterations are linked to substrate ubiquitination in cells. This has
      implications for understanding the recognition of misfolded proteins during aging
      and in human diseases such as cancer.

PMID- 16579793
TI  - Identification of norharman as the cytotoxic compound produced by the sponge
      (Hymeniacidon perleve)-associated marine bacterium Pseudoalteromonas piscicida
      and its apoptotic effect on cancer cells.
AB  - Marine invertebrates harbour a wealth of micro-organisms in their bodies. Most of
      these micro-organisms can catabolize antibiotic compounds as chemical-defence
      compounds. These compounds not only play an important protective role for their
      producer and for their hosts, but also have high potential in medicinal
      applications. In order to discover natural anticancer products, 29 marine
      bacterial strains have been isolated from the sponge Hymeniacidon perleve,
      samples of which were collected from the intertidal zone during low tide off
      Nanji island in Eastern China. By means of a cytotoxicity bioassay, one strain,
      NJ6-3-1, with significant cytotoxic activity, was selected for culture in a 30
      litre fermentation tank. The major cytotoxic compound in the metabolites of NJ6-3
      1, separated by means of a bioassay-guided fractionation process, has been
      identified as norharman (a beta-carboline alkaloid) by electron-impact MS and NMR
      analyses. Norharman showed cytotoxicity towards both the HeLa cervical-cancer
      cell line and the BGC-823 stomach-cancer cell line, with an IC(50) of 5
      microg/ml. Several methods were used to study the mechanism by which norharman is
      cytotoxic to HeLa cells. By means of an Acridine Orange/ethidium bromide dual
      staining assay, condensation of chromatin was observed. A TUNEL (terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay showed
      degradation of DNA. Flow-cytometric analysis indicated that norharman could
      arrest cells at the G(2)/M phase of the cell cycle. These results demonstrate the
      cytotoxic mechanism of norharman involves the induction of apoptosis in HeLa
      cells.

PMID- 16579796
TI  - Does size matter? It depends on how the analysis is done.

PMID- 16579797
TI  - Fertility-sparing treatment of a primary retroperitoneal mucinous
      cystadenocarcinoma.

PMID- 16579798
TI  - The role of colposcopy in the follow up of women treated for cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: To determine the effect of colposcopy on the sensitivity and
      specificity of follow-up procedures in the detection of residual or recurrent
      disease after treatment for cervical intraepithelial neoplasia (CIN). DESIGN: A
      retrospective study of information held in a colposcopy database. SETTING: A
      teaching hospital colposcopy clinic. POPULATION: A total of 2244 women treated in
      Hammersmith Hospital for histologically confirmed CIN between 1 January 1988 and
      31 December 2002. METHODS: Data from the records of women treated with some form
      of local conservative therapy for CIN1-CIN3 between January 1988 and December
      2002 were extracted from the colposcopy database. Women with histological
      confirmation of post-treatment disease were identified. MAIN OUTCOME MEASURES:
      The sensitivity and specificity of cytology alone was compared with the
      sensitivity and specificity of the combination of colposcopy and cytology.
      RESULTS: Colposcopy improved the sensitivity of cytology for the detection of
      high-grade disease from 64 to 91% but reduced the specificity from 95 to 88%.
      With a 3% rate of post-treatment high-grade disease, colposcopy detected 8 extra
      cases per 1000 women but resulted in 88 more false alarms per 1000 women. Among
      women in whom the treatment margins were involved or uncertain, colposcopy
      detected 13 extra cases per 1000 women but resulted in 12 fewer false alarms per
      1000 women because the prevalence of post-treatment disease was higher.
      CONCLUSIONS: Colposcopy does improve the detection rate of post-treatment disease
      but at a cost of additional false alarms. The benefit of colposcopy will be
      greater in high-risk groups of women with higher rates of treatment failure.

PMID- 16579799
TI  - Intrauterine fetal demise following laser treatment in twin-to-twin transfusion
      syndrome.
AB  - OBJECTIVE: To evaluate the incidence, risk factors and consequences of
      intrauterine fetal demise (IUFD) of at least one twin in twin-to-twin transfusion
      syndrome (TTTS) treated by laser. DESIGN: Retrospective analysis. SETTING:
      Experience of a single centre between 1999 and 2004. POPULATION: A subgroup of 45
      cases with fetal demise of one or both twins from a series of 120 cases of TTTS
      treated by laser. METHODS: All cases were entered prospectively into a dedicated
      database and the results were analysed retrospectively. MAIN OUTCOME MEASURES:
      Fetal demise prognostic factors, survival, fetal anaemia, brain lesions, neonatal
      death and intact survival. RESULTS: IUFD of one twin occurred in 40 of 120 cases
      (19 donors and 21 recipients). IUFD of both twins occurred in another five cases.
      From these 40 cases, miscarriage occurred in two and pregnancy termination was
      requested in another two cases because of antenatal brain lesions. Two neonates
      died and two presented severe morbidity, survivors were therefore neurologically
      normal at 6-44 months of life in 89% (32/36) of the cases. Univariate analysis
      showed that preoperative abnormal umbilical artery Doppler in the donor before
      laser treatment and in the recipient following laser treatment was associated
      with their demise. Incomplete coagulation was suspected in cases where anaemia or
      cerebral lesions developed following the death of the first twin (10).
      CONCLUSIONS: IUFD of one or both twins occurred in 45 of 120 (38%) cases of
      severe TTTS treated by laser. In these, separation of the placental circulations
      was incomplete in at least 22% (10/45) of the cases. Umbilical artery Doppler
      abnormalities before laser were found to be risk factors for the donors' demise
      following the procedure.

PMID- 16579801
TI  - Pregnancy-induced hypertension is associated with lower infant mortality in
      preterm singletons.
AB  - OBJECTIVE: To assess the association between pregnancy-induced hypertension (PIH)
      and infant mortality. DESIGN: Retrospective cohort study. SETTING: Birth and
      infant death registration dataset of the USA. POPULATION: A total of 17,432,987
      eligible, liveborn singleton births in 1995-2000. METHODS: Multivariate logistic
      regression was applied to evaluate the association between PIH and infant
      mortality, with adjustment of potential confounders. MAIN OUTCOME MEASURES:
      Infant death (0-364 days) and its three components: early neonatal death (0-6
      days), late neonatal death (7-27 days), and postneonatal death (28-364 days).
      RESULTS: There was a significant reduction in infant mortality associated with
      PIH in early preterm infants (OR = 0.59, 95% CI: 0.56-0.63) and in late preterm
      infants (OR = 0.80, 95% CI: 0.73-0.87), but a significant increase in term
      infants (OR = 1.08, 95% CI: 1.02-1.14). Both in early preterm and late preterm
      births, early neonatal mortality (OR = 0.38, 95% CI: 0.34-0.42; OR = 0.68, 95%
      CI: 0.61-0.77) and late neonatal mortality (OR = 0.59, 95% CI: 0.50-0.70; OR =
      0.76, 95% CI: 0.61-0.96) were decreased in infants born to mothers with PIH
      compared with those born to mothers with normal blood pressure. The PIH
      associated reduction in neonatal mortality among preterm singletons was stronger
      in small-for-gestational-age infants than in normal growth infants and stronger
      in infants born to nulliparous women than in those born to multiparous women.
      CONCLUSIONS: PIH is associated with lower risk of infant death in preterm births
      but higher risk in term births.

PMID- 16579800
TI  - Association of pre-eclampsia with the R563Q mutation of the beta-subunit of the
      epithelial sodium channel.
AB  - The R563Q mutation of the beta-subunit of the epithelial sodium channel (ENaC) is
      associated with hypertension in black and mixed ancestry (MA) men and women in
      South Africa. The frequency of the R563Q mutation in black and MA women with pre
      eclampsia (n= 230) and in controls (n= 198) was studied. The R563Q mutation was
      found in 7.8% of the women with pre-eclampsia and in 2.6% of controls (P= 0.014).
      This remained significant if the black women were analysed separately (P= 0.031).
      We have demonstrated that a genetic variant of the ENaC is associated with pre
      eclampsia. This has implications for understanding the pathogenesis and treatment
      of pre-eclampsia.

PMID- 16579802
TI  - Fish oil in various doses or flax oil in pregnancy and timing of spontaneous
      delivery: a randomised controlled trial.
AB  - OBJECTIVES: To test the earlier suggested hypothesis that intake of long-chain n
      3 fatty acids from fish oil may delay the timing of spontaneous delivery and to
      test if alpha-linolenic acid, provided as flax oil capsules, shows the same
      effect. DESIGN: Randomised controlled trial including women reporting low dietary
      fish intake. The women were allocated in the proportions of 1:1:1:1:1:1:2 into
      six treatment groups and a control group, respectively, from week 17-27 of
      gestation. The treatment groups received fish oil, in various doses, or flax oil,
      and the control group did not receive any treatment. SETTING: The Danish National
      Birth Cohort. SAMPLE: A total of 3098 women allocated into six treatment groups
      and one control group. METHODS: The six intervention groups were offered fish oil
      capsules in doses of 0.1, 0.3, 0.7, 1.4 and 2.8 g of eicosapentaenoic acid and
      docosahexaenoic acid per day or 2.2 g of alpha-linolenic acid (ALA) per day from
      week 17-27 of gestation until delivery. MAIN OUTCOME MEASURES: Timing of
      spontaneous delivery. RESULTS: No differences in timing of spontaneous delivery
      was detected in the fish oil groups or the flax oil group, compared with the
      control group. The difference in timing of spontaneous delivery in the group
      receiving the highest fish oil dose compared with the control group was 0.8 days
      (95% CI: -2.3 to 1.0). Only a minority of the women in the intervention groups
      took capsules until delivery. CONCLUSION: Possible explanations for these
      findings include no true effect of n-3 fatty acids on spontaneous delivery or a
      quick-acting effect not detectable in this trial.

PMID- 16579803
TI  - Randomised trial of vitamin A supplementation in pregnant women in rural Malawi
      found to be anaemic on screening by HemoCue.
AB  - OBJECTIVE: To assess the effects of vitamin A supplementation in women with
      anaemia during pregnancy. DESIGN: Single-centre randomised controlled trial.
      SETTING: Rural community in southern Malawi, central Africa. POPULATION: Seven
      hundred women with singleton pregnancies at 12-24 weeks measured by ultrasound
      scan and with haemoglobin <11.0 g/dl by HemoCue screening method. Analysis was by
      intention to treat. All received iron and folate, and sulphadoxine/pyrimethamine
      for antimalarial prophylaxis. METHODS: Women were randomised to receive oral
      supplementation with daily 5000 or 10,000 iu vitamin A, or placebo. MAIN OUTCOME
      MEASURES: Anaemia, as assessed by Coulter counter, severe anaemia, iron status
      and indices of infection. RESULTS: Vitamin A deficiency was, in this rural
      population, less common than predicted. Vitamin A supplementation had no
      significant impact on anaemia, severe anaemia, iron status and indices of
      infection. Vitamin A stores were less likely to be depleted at the end of
      pregnancy in supplemented groups. CONCLUSIONS: Vitamin A supplementation
      programmes to reduce anaemia should not be implemented in similar antenatal
      populations in rural sub-Saharan Africa unless evidence emerges of positive
      benefit on substantive clinical outcomes. Introducing public health interventions
      of unknown benefit and with unclear biological mechanisms can divert scarce
      resources from clinical and social interventions more likely to impact maternal
      mortality.

PMID- 16579804
TI  - Is intrapartum temporary pacing required for women with complete atrioventricular
      block? An analysis of seven cases.
AB  - Women with complete atrioventricular heart block without a permanent pacemaker
      normally receive temporary pacing for labour and birth. Here, we report seven
      women who were managed without pacing. All women had a temporary pacing lead
      inserted prior to induction of labour, but none of the women required pacing
      during labour or birth. Our experience suggests that women with complete
      atrioventricular block and without permanent pacing do not routinely require
      temporary pacing for labour and birth.

PMID- 16579805
TI  - Vaginal delivery can be considered in monochorionic diamniotic twins.
AB  - The outcomes of 60 sets of monochorionic diamniotic (MCDA) twins were compared
      with 218 sets of dichorionic diamniotic (DCDA) twins. The caesarean section rates
      for MCDA were similar to those for DCDA twins (56.6 versus 53.6%, P > 0.1).
      Although the number of babies with 5-minute Apgar score of <7 was significantly
      higher for vaginally delivered MCDA twins compared with that of DCDA twins (12
      versus 3.5%, P < 0.001), the umbilical artery pH of <7.2 was similar (20 versus
      13%, P > 0.05). Admission to neonatal intensive care unit (NICU) and neonatal
      mortality were also similar in both groups. Delivery by caesarean section was
      associated with increased admission to the NICU and neonatal mortality for MCDA
      twins when compared with vaginal delivery group. From this retrospective cohort
      study, we can conclude that vaginal delivery for MCDA twins appeared to be a
      reasonable management option when similar selection criteria for vaginal delivery
      of DCDA twins were applied.

PMID- 16579806
TI  - Morphometric placental villous and vascular abnormalities in early- and late
      onset pre-eclampsia with and without fetal growth restriction.
AB  - OBJECTIVE: To evaluate placental morphology in pregnancies complicated by early-
      and late-onset pre-eclampsia (PET) with and without fetal growth restriction
      (FGR) using stereological techniques. DESIGN: A total of 69 pregnant women were
      studied. Twenty women had pregnancies complicated by PET, 17 by FGR and 16 by
      both PET and FUR; the remaining 16 were from gestational-age-matched controls.
      Each group was further classified into early onset (<34 weeks) and late onsets
      (>34 weeks) based on gestational ages. SETTING: NPIMR at Northwick Park and St
      Marks Hospital. POPULATION: placentae from pregnant women. METHODS: Formalin
      fixed, wax-embedded sections stained with anti-CD34 antibodies and counterstained
      with haematoxylin. MAIN OUTCOME MEASURES: Volumes, surface areas, lengths,
      diameters and shape factors of the villous tissues and fetal vasculature in the
      intermediate and terminal villi of all the groups studied. RESULTS: Terminal
      villi volume and surface area were compromised in early-onset PET cases, late
      onset PET had no impact on peripheral villi or vasculature features. The
      morphology of the vascular and villous subcomponents in the intermediate and
      terminal villi was significantly influenced by late-onset FGR, whereas early
      onset FGR caused a reduction in placental weight. Length estimates were not
      influenced by PET, FGR or age of onset. Intermediate arteriole shape factor was
      significantly reduced in late-onset FGR. CONCLUSIONS: Isolated early-onset PET
      was associated with abnormal placental morphology, but placentas from late-onset
      PET were morphologically similar to placentas from gestational-age-matched
      controls, confirming the existence of two subsets of this condition and
      supporting the hypothesis that late-onset PET is a maternal disorder and not a
      placental disease.

PMID- 16579807
TI  - Reducing blood loss at open myomectomy using triple tourniquet: a randomised
      controlled trial.

PMID- 16579808
TI  - Ultrastructural description of Breviata anathema, n. gen., n. sp., the organism
      previously studied as "Mastigamoeba invertens".
AB  - An understanding of large-scale eukaryotic evolution is beginning to crystallise,
      as molecular and morphological data demonstrate that eukaryotes fall into six
      major groups. However, there are several taxa of which the affinities are yet to
      be resolved, and for which there are only either molecular or morphological data.
      One of these is the amoeboid flagellate Mastigamoeba invertens. This organism was
      originally misidentified and studied as a pelobiont using molecular data. We
      present its first light microscopical and ultrastructural characterisation. We
      demonstrate that it does not show affinities to the amoebozoan pelobionts,
      because unlike the pelobionts, it has a double basal body and two flagellar
      roots, a classical Golgi stack, and a large branching double membrane-bound
      organelle. Phylogenetic analyses of small subunit ribosomal RNA suggest an
      affinity with the apusomonads, when a covariotide correction for rate
      heterogeneity is used. We suggest that previous molecular results have been
      subject to artefacts from an insufficient correction for rate heterogeneity. We
      propose a new name for the taxon, Breviata anathema; and the unranked, apomorphy
      based name "Breviates" for Breviata and its close relatives.

PMID- 16579809
TI  - Identification of three distinct Polytomella lineages based on mitochondrial DNA
      features.
AB  - Polytomella is composed of colorless green algae closely related to Chlamydomonas
      reinhardtii. Species in the genus have been used in diverse fields of biological
      research, most recently to study mitochondrial function and mitochondrial genome
      evolution in the Chlorophyceae, but the phylogenetic relationship between the
      various available taxa has not yet been clarified and it is not known whether
      they also possess fragmented mitochondrial genomes, as reported for Polytomella
      parva. We therefore examined cox1 sequence from seven Polytomella taxa with the
      goal of establishing their phylogenetic relationships and relating this
      information to their mitochondrial DNA (mtDNA) fragmentation pattern. We found
      that the Polytomella isolates examined fall into three distinct lineages, two of
      which possess fragmented mitochondrial genomes. The third and earliest branching
      lineage, represented by Polytomella capuana, appears to possess an intact mtDNA.
      In addition, there is evidence for variation in both size and number of mtDNA
      fragments between various Polytomella isolates, even within the same lineage. The
      considerable amount of sequence divergence between lineages seems to correlate
      with the geographic origin of the strains, leading us to believe that greater
      amounts of sequence divergence could be uncovered by a broader sampling of
      Polytomella.

PMID- 16579810
TI  - Two new species of Epistylis (Ciliophora: Peritrichida) on the blue crab
      (Callinectes sapidus) in the Gulf of Mexico.
AB  - Two epibiotic peritrichs infested the blue crab, Callinectes sapidus, from the
      Gulf of Mexico, Mississippi, USA. Epistylis callinectes n. sp. was isolated from
      the epipods of maxillipeds, bases of gill-cleaning setae, and gills, and
      Epistylis clampi n. sp. was isolated from the exterior surfaces of the
      exoskeleton. Epistylis callinectes has short, symmetrically and dichotomously
      branched stalks; its zooid is elongate ovoid and conspicuously longer than the
      individual stalk branches, measuring 40-57 (49) x 18-33 (26) microm in vivo and
      containing a thick, undivided peristomial lip (PL). It has a single contractile
      vacuole and a transverse horseshoe-shaped macronucleus. Its haplokinety (H) and
      polykinety (Po) complete one and one-half circuits on the peristome before
      entering the infundibulum. There is a distal kinetal fragment present at the
      distal end of both the H and Po. Epistylis callinectes has 48-70 transverse
      silverlines from the oral area to the trochal band (TB) and 19-26 from the TB to
      the scopula. Epistylis clampi has long, asymmetrically, and dichotomously
      branched stalks. Its zooid is elongate vase-shaped, measuring 35-64 (48) x 21-30
      (27) microm in vivo and with a thick, transversely folded PL. The stalks
      supporting zooids are unequal in length. Its zooid has a single contractile
      vacuole and a transverse horseshoe-shaped macronucleus occurs in the upper half
      of the body. Its H and Po complete approximately one circuit around the peristome
      before entering the infundibulum. There is a distal kinetal fragment present at
      the distal end of both the H and Po. This species has 71-112 transverse
      silverlines from the peristome to the scopula.

PMID- 16579811
TI  - Analysis of fruiting body development in the aggregative ciliate Sorogena
      stoianovitchae (Ciliophora, Colpodea).
AB  - The fruiting body-forming ciliate Sorogena stoianovitchae is a protist that is
      multicellular in one stage of its life cycle. When nutrient levels are depleted,
      a number of Sorogena cells aggregate beneath the water surface to form an aerial
      fruiting body. Based on morphologies and the inhibition of protein synthesis,
      fruiting body development is divided into five distinct stages: (1) aggregation
      before sunrise, (2) compact aggregation after sunrise, (3) secretion of mucous
      matrix, (4) stalk-elongation, and (5) completion of the fruiting-body. In the
      aggregation stage, the cells were trapped in a matrix material that stained
      orange with 4',6-diamino-2-phenylindole (DAPI), but differed from the mucous
      matrix in the later stage. A short interruption of the dark period, at 6-8 h
      after the onset of dark, inhibited fruiting body development. Irrespective of the
      length of the dark period (10-16 h), the cells remained in the aggregation stage
      until the beginning of the light period. Therefore, an uninterrupted dark period
      of more than 8 h is critical for the initial aggregation of cells, but subsequent
      development is triggered by light.

PMID- 16579813
TI  - Andalucia (n. gen.)--the deepest branch within jakobids (Jakobida; Excavata),
      based on morphological and molecular study of a new flagellate from soil.
AB  - A new heterotrophic flagellate (Andalucia godoyi n. gen. n. sp.) is described
      from soil. Earlier preliminary 18S rRNA analyses had indicated a relationship
      with the phylogenetically difficult-to-place jakobid Jakoba incarcerata.
      Andalucia godoyi is a small (3-5 mum) biflagellated cell with a ventral feeding
      groove. It has tubular mitochondrial cristae. There are two major microtubular
      roots (R1, R2) and a singlet root associated with basal body 1 (posterior). The
      microtubular root R1 is associated with non-microtubular fibres "I,""B," and "A,"
      and divides in two parts, while R2 is associated with a "C" fibre. These
      structures support the anterior portion of the groove. Several features of A.
      godoyi are characteristic of jakobids: (i) there is a single dorsal vane on
      flagellum 2; (ii) the C fibre has the jakobid multilaminate substructure; (iii)
      the dorsal fan of microtubules originates in very close association with basal
      body 2; and (iv) there is no "R4" microtubular root associated with basal body 2.
      Morphological analyses incorporating the A. godoyi data strongly support the
      monophyly of all jakobids. Our 18S rRNA phylogenies place A. godoyi and J.
      incarcerata as a strong clade, which falls separately from other jakobids.
      Statistical tests do not reject jakobid monophyly, but a specific relationship
      between Jakoba libera and J. incarcerata and/or A. godoyi is rejected. Therefore,
      we have established a new genus Andalucia n. gen. with the type species Andalucia
      godoyi n. sp., and transfer Jakoba incarcerata to Andalucia as Andalucia
      incarcerata n. comb.

PMID- 16579812
TI  - An integrated morphological and molecular approach to a new species description
      in the Trypanosomatidae: the case of Leptomonas podlipaevi n. sp., a parasite of
      Boisea rubrolineata (Hemiptera: Rhopalidae).
AB  - Leptomonas podlipaevi n. sp., a new trypanosomatid species, is described herein
      based on light microscopic, ultrastructural, and molecular phylogenetic data. The
      organism is pleomorphic both in host and culture, with two predominant forms-a
      typical promastigote with a long flagellum and a shorter promastigote with a
      small or barely extending flagellum. Several spliced leader RNA repeat sequences
      obtained from the original cultures and the clonal lines representing two types
      of cells were all nearly identical. These sequences formed a tight cluster in the
      neighbor-joining tree well separated from other trypanosomatid species.
      Glyceraldehyde phosphate dehydrogenase gene sequences were determined for L.
      podlipaevi and 10 previously described trypanosomatid species. Molecular
      phylogenetic analysis has demonstrated that the new species is most closely
      related to Leptomonas seymouri and Leptomonas pyrrhocoris. The analysis has also
      highlighted the polyphyly of the genus Leptomonas.

PMID- 16579814
TI  - In-vitro activity of miltefosine and voriconazole on clinical isolates of free
      living amebas: Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri.
AB  - The anticancer agent miltefosine and the antifungal drug voriconazole were tested
      in vitro against Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria
      fowleri. All three amebas are etiologic agents of chronic (Balamuthia,
      Acanthamoeba) or fulminant (Naegleria) encephalitides in humans and animals and,
      in the case of Acanthamoeba, amebic keratitis. Balamuthia exposed to <40 microm
      concentrations of miltefosine survived, while concentrations of >or=40 microM
      were generally amebacidal, with variation in sensitivity between strains. At
      amebastatic drug concentrations, recovery from drug effects could take as long as
      2 weeks. Acanthamoeba spp. recovered from exposure to 40 microM, but not 80
      microM miltefosin. Attempts to define more narrowly the minimal inhibitory (MIC)
      and minimal amebacidal concentrations (MAC) for Balamuthia and Acanthamoeba were
      difficult due to persistence of non-proliferating trophic amebas in the medium.
      For N. fowleri, 40 and 55 microM were the MIC and MAC, respectively, with no
      trophic amebas seen at the MAC. Voriconazole had little or no inhibitory effect
      on Balamuthia at concentrations up to 40 microg/ml, but had a strong inhibitory
      effect upon Acanthamoeba spp. and N. fowleri at all drug concentrations through
      40 microg/ml. Following transfer to drug-free medium, Acanthamoeba polyphaga
      recovered within a period of 2 weeks; N. fowleri amebas recovered from exposure
      to 1 microg/ml, but not from higher concentrations. All testing was done on
      trophic amebas; drug sensitivities of cysts were not examined. Miltefosine and
      voriconazole are potentially useful drugs for treatment of free-living amebic
      infections, though sensitivities differ between genera, species, and strains.

PMID- 16579815
TI  - Intestinal expression of H+ V-ATPase in the mosquito Aedes albopictus is tightly
      associated with gregarine infection.
AB  - Vacuolar ATPase (V-ATPase) is a family of ATP-dependent proton pumps expressed on
      the plasma membrane and endomembranes of eukaryotic cells. Acidification of
      intracellular compartments, such as lysosomes, endosomes, and parasitophorous
      vacuoles, mediated by V-ATPase is essential for the entry by many enveloped
      viruses and invasion into or escape from host cells by intracellular parasites.
      In mosquito larvae, V-ATPase plays a role in regulating alkalization of the
      anterior midgut. We extracted RNA from larval tissues of Aedes albopictus, cloned
      the full-length sequence of mRNA of V-ATPase subunit A, which contains a poly-A
      tail and 2,971 nucleotides, and expressed the protein. The fusion protein was
      then used to produce rabbit polyclonal antibodies, which were used as a tool to
      detect V-ATPase in the midgut and Malpighian tubules of mosquito larvae. A
      parasitophorous vacuole was formed in the midgut in response to invasion by
      Ascogregarina taiwanensis, confining the trophozoite(s). Acidification was
      demonstrated within the vacuole using acridine orange staining. It is concluded
      that gregarine sporozoites are released by ingested oocysts in the V-ATPase
      energized high-pH environment. The released sporozoites then invade and develop
      in epithelial cells of the posterior midgut. Acidification of the parasitophorous
      vacuoles may be mediated by V-ATPase and may facilitate exocytosis of the vacuole
      confining the trophozoites from the infected epithelial cells for further
      extracellular development.

PMID- 16579816
TI  - Effect of Japanese Paramecium bursaria extract on photosynthetic carbon fixation
      of symbiotic algae.
AB  - To investigate the relationship between the Japanese Paramecium bursaria host and
      its symbiont, we studied the effect of a host cell-free extract on carbon
      fixation and photosynthate release of the symbiont. The host extract enhanced
      symbiotic algal carbon fixation about 3-fold at an increased concentration;
      however, release of photosynthate hardly changed. Since the enhancing effect was
      not affected by elimination of carbon dioxide from the host extract, the
      existence of a host factor that stimulates algal carbon fixation was made clear.
      The host factor is a heat-stable, low molecular weight substance. In relation to
      the pH dependence, the extract improved carbon fixation at acidic and neutral pH
      and showed almost no effect at pH 9.0. Therefore, the stimulation of carbon
      fixation by the host factor is unlikely to be caused by intracellular pH change.
      The extract also improved carbon fixation of several Chlorella species, symbiotic
      and free-living, and apparently exhibited no species specificity. Therefore, the
      host seems to regulate the photosynthesis of the symbiont via a specific
      compound.

PMID- 16579817
TI  - Isolation and characterization of proliferating cell nuclear antigen from the
      dinoflagellate Pfiesteria piscicida.
AB  - Proliferating cell nuclear antigen (PCNA), a co-factor of DNA polymerases delta
      and epsilon, is essential for DNA replication and repair. Understanding the
      structure and expression characteristics of this gene in dinoflagellates would
      enable us to gain insights into how the cell cycle in these enigmatic eukaryotes
      is regulated and whether this gene can be a growth marker of these ecologically
      important organisms. We analyzed pcna and its encoded protein from Pfiesteria
      piscicida (Ppi_PCNA). Using reverse transcription-polymerase chain reaction (RT
      PCR) and RNA ligase mediated-rapid amplification of cDNA ends (RLM-RACE) methods,
      Ppi_pcna cDNA was isolated; it contained a coding region for 258 amino acid
      residues (aa) preceded by various 5'- and 3'-untranslated ends. The deduced
      protein length was similar to that of typical vertebrate and plant PCNA. PCR
      using genomic DNA as the template yielded multiple products whose sequences
      revealed multiple copies of pcna in tandem repeats separated by an unknown
      sequence. Using real-time PCR, we estimated 41+/-7 copies of this gene in each P.
      piscicida cell. Reverse transcription real-time PCR indicated a similar pcna mRNA
      level between the exponential and the stationary growth phases. Western blot
      analysis revealed a slightly higher PCNA level (<2-fold) in the exponential than
      in the stationary growth phases. We conclude that (1) P. piscicida possesses a
      typical eukaryote PCNA; (2) unlike in other eukaryotes, pcna in P. piscicida
      occurs in multiple copies arranged in tandem; and (3) regulation of P. piscicida
      PCNA probably lies in post-translational modification.

PMID- 16579818
TI  - Vaccination with gamma-irradiated Neospora caninum tachyzoites protects mice
      against acute challenge with N. caninum.
AB  - Neospora caninum, an apicomplexan parasite, is a leading cause of bovine
      abortions worldwide. The efficacy of gamma-irradiated N. caninum strain NC-1
      tachyzoites as a vaccine for neosporosis was assessed in C57BL6 mice. A dose of
      528 Gy of gamma irradiation was sufficient to arrest replication but not host
      cell penetration by tachyzoites. Female C57BL6 mice were vaccinated with two
      intraperitoneal inoculations of 1 x 10(6) irradiated tachyzoites at 4-wk
      intervals. When stimulated with N. caninum tachyzoite lysates, splenocytes of
      vaccinated mice, cultured 5 and 10 wk after vaccination, secreted significant
      (P<0.05) levels of interferon gamma, interleukin (IL)-10, and small amounts of IL
      4. Antibody isotype-specific ELISA of sera from vaccinated mice exhibited both
      IgG1 and IgG2a isotypes of antibodies. Vaccinated mice were challenged
      intraperitoneally with 2 x 10(7)N. caninum tachyzoites. All vaccinated mice
      remained healthy and showed no obvious signs of neosporosis up to the 25th day
      post-challenge when the study was terminated. All unvaccinated control mice died
      within 1 wk of infection. Gamma-irradiated N. caninum tachyzoites can serve as an
      effective, attenuated vaccine for N. caninum.

PMID- 16579819
TI  - Rigorous disease management evaluation.

PMID- 16579820
TI  - Evaluating disease management programme effectiveness: an introduction to the
      regression discontinuity design.
AB  - Although disease management (DM) has been in existence for over a decade, there
      is still much uncertainty as to its effectiveness in improving health status and
      reducing medical cost. The main reason is that most programme evaluations
      typically follow weak observational study designs that are subject to bias, most
      notably selection bias and regression to the mean. The regression discontinuity
      (RD) design may be the best alternative to randomized studies for evaluating DM
      programme effectiveness. The most crucial element of the RD design is its use of
      a 'cut-off' score on a pre-test measure to determine assignment to intervention
      or control. A valuable feature of this technique is that the pre-test measure
      does not have to be the same as the outcome measure, thus maximizing the
      programme's ability to use research-based practice guidelines, survey instruments
      and other tools to identify those individuals in greatest need of the programme
      intervention. Similarly, the cut-off score can be based on clinical understanding
      of the disease process, empirically derived, or resource-based. In the RD design,
      programme effectiveness is determined by a change in the pre-post relationship at
      the cut-off point. While the RD design is uniquely suitable for DM programme
      evaluation, its success will depend, in large part, on fundamental changes being
      made in the way DM programmes identify and assign individuals to the programme
      intervention.

PMID- 16579821
TI  - Measuring diagnostic and predictive accuracy in disease management: an
      introduction to receiver operating characteristic (ROC) analysis.
AB  - Diagnostic or predictive accuracy concerns are common in all phases of a disease
      management (DM) programme, and ultimately play an influential role in the
      assessment of programme effectiveness. Areas, such as the identification of
      diseased patients, predictive modelling of future health status and costs and
      risk stratification, are just a few of the domains in which assessment of
      accuracy is beneficial, if not critical. The most commonly used analytical model
      for this purpose is the standard 2 x 2 table method in which sensitivity and
      specificity are calculated. However, there are several limitations to this
      approach, including the reliance on a single defined criterion or cut-off for
      determining a true-positive result, use of non-standardized measurement
      instruments and sensitivity to outcome prevalence. This paper introduces the
      receiver operator characteristic (ROC) analysis as a more appropriate and useful
      technique for assessing diagnostic and predictive accuracy in DM. Its advantages
      include; testing accuracy across the entire range of scores and thereby not
      requiring a predetermined cut-off point, easily examined visual and statistical
      comparisons across tests or scores, and independence from outcome prevalence.
      Therefore the implementation of ROC as an evaluation tool should be strongly
      considered in the various phases of a DM programme.

PMID- 16579822
TI  - Strengthening the case for disease management effectiveness: un-hiding the hidden
      bias.
AB  - As is the case with most health care program evaluations, disease management (DM)
      programs typically follow an observational study design, indicating that
      randomization to treatment or control was not performed. The foremost limitation
      of observational studies, compared to randomized studies, is that the only biases
      that can be controlled for are those associated with observed variables. Hidden
      bias refers to all those unobserved covariates that may distort the conclusions
      of the study. This paper introduces a sensitivity analysis that is used to
      determine the magnitude of hidden bias necessary to alter the conclusion that a
      DM program intervention was indeed effective.

PMID- 16579823
TI  - Evaluating disease management programme effectiveness: an introduction to
      instrumental variables.
AB  - This paper introduces the concept of instrumental variables (IVs) as a means of
      providing an unbiased estimate of treatment effects in evaluating disease
      management (DM) programme effectiveness. Model development is described using zip
      codes as the IV. Three diabetes DM outcomes were evaluated: annual diabetes
      costs, emergency department (ED) visits and hospital days. Both ordinary least
      squares (OLS) and IV estimates showed a significant treatment effect for diabetes
      costs (P = 0.011) but neither model produced a significant treatment effect for
      ED visits. However, the IV estimate showed a significant treatment effect for
      hospital days (P = 0.006) whereas the OLS model did not. These results illustrate
      the utility of IV estimation when the OLS model is sensitive to the confounding
      effect of hidden bias.

PMID- 16579824
TI  - Referral to and discharge from cardiac rehabilitation: key informant views on
      continuity of care.
AB  - OBJECTIVES: To assess the system-level barriers and facilitators of continuity of
      care from acute care to cardiac rehabilitation (CR), and from CR discharge to
      follow-up with primary health care providers. METHOD: Semi-structured individual
      interviews with 24 key informants including CR staff, research scientists, policy
      makers, cardiologists and other doctors from a regional to international level
      were conducted regarding the processes of referral to and discharge from cardiac
      rehabilitation. Key informant interviews were audio taped, transcribed, and
      imported into QSR N6 software for Grounded analysis. RESULTS: Themes that emerged
      related to communication, referral and discharge processes, health care provider
      practices, inter- and intra-institutional relationships, and alternative models
      of delivery to improve continuity. CONCLUSIONS: Ramifications for enhancing
      referral of patients to beneficial CR services and follow-up by primary care
      providers to ensure maintenance of functional and health-related gains are
      discussed.

PMID- 16579825
TI  - Quality and productive efficiency in simple laceration treatment.
AB  - OBJECTIVES: The surgical management and outcome of outpatient care for patients
      with simple lacerations were compared across three institutions. We examined the
      variations in wound infection rate, total charge and medical resource use in
      terms of prophylactic antibiotic prescription, frequency of outpatient visits and
      required days for stitch removal. DESIGN: Retrospective and consecutive chart
      review. STUDY PARTICIPANTS: Patients receiving treatment for simple lacerations
      in the outpatient departments of three institutions in Japan between June 2000
      and August 2001. OUTCOME MEASURES AND METHOD: The basic patient characteristics,
      treatment method for the laceration and incidence of wound infection were
      collected. Variations in the wound infection rate were examined across the
      institutions. We then examined the variations in the medical resource use and
      total charge for patients without wound infection among the institutions by
      multiple linear regression model. RESULTS: A total of 479 patients were reviewed.
      The proportion of patients with blunt injury, patients with simple lacerations to
      the head or face, and those with underlying medical disease were significantly
      different among the three institutions. The wound infection rate did not
      significantly differ (1.9% in Institution A, 1.3% in B, 3.0% in C, P = 0.555).
      The medical resource use for patients without wound infection was significantly
      different and small in Institution A. CONCLUSION: We identified variations in the
      resource use for completing wound care among three institutions, whereas the
      wound infection rate revealed no significant difference among the institutions.
      There existed some room for improvement in the productive efficiency of simple
      laceration treatment.

PMID- 16579826
TI  - Understanding and overcoming the barriers of implementing patient decision aids
      in clinical practice.
AB  - Patient decision aids (ptDAs) have been developed to assist patients with
      difficult health-related decisions. Despite their proven effects on decision
      quality in numerous efficacy trials, we lack an evidence-based approach for
      implementing them as part of the process of care. Pragmatic trials of ptDAs have
      uncovered a myriad of implementation challenges; therefore we need a better
      understanding of the barriers and strategies to overcome them to facilitate their
      widespread uptake. The following paper provides an overview of the barriers
      related to the uptake of ptDAs within the process of care and the strategies,
      opportunities and research priorities to overcome them. This report is based on
      our interpretation of the literature and our collective experience in
      implementing ptDAs within trials and other contexts.

PMID- 16579827
TI  - Teamwork in the operating theatre: cohesion or confusion?
AB  - RATIONALE: The aim of the research that we report here was to empirically assess
      the cohesiveness of the multidisciplinary operating theatre (OT) team. METHOD: We
      used concepts from the team performance and team mental models literature to
      assess OT professionals' perceptions of their teamwork, the structure of their
      teams and their respective roles within them and their teams' performance.
      RESULTS: Team structure: OT professionals would welcome a change from the current
      structure of the team, although there was no agreement on what that structure is.
      Nurses perceived the team as unitary, surgeons and anaesthetists perceived it as
      comprising multiple subteams. Team roles: OT professionals tended to overrate
      their own understanding of their colleagues' role in the OT relative to the role
      understanding that the colleagues attributed to them. This tendency was
      especially marked for the surgeons. Team communication and team performance: OT
      professionals agreed on the relative importance of the various communicating
      pairs in the OT. Moreover, they were satisfied with the quality of communication
      among them, except for the communication between the surgeon and the
      anaesthetist, which received lower ratings. Finally, the quality of the teamwork
      in the OT was deemed acceptable, although there is room for improvement.
      CONCLUSIONS: The OT environment need not be as cohesive as previously assumed--a
      finding that carries implications for the effectiveness of team training
      interventions. Further research is needed in order to fully comprehend the
      dynamics of the OT as a working environment and, most importantly, their relation
      to patient safety.

PMID- 16579828
TI  - The impact of implantable cardiac defibrillators for primary prophylaxis in the
      community: baseline risk and clinically meaningful benefits.
AB  - OBJECTIVE: To estimate the baseline risk of arrhythmic death required for
      prophylactic implantable cardiac defibrillators (ICDs) to result in clinically
      meaningful survival benefits in the population. BACKGROUND: While proven
      efficacious, the absolute survival impact of ICDs for the primary prevention of
      sudden cardiac death among patients with left ventricular (LV) dysfunction is
      highly dependent upon patient's baseline risk of arrhythmic death. METHODS: Using
      echocardiographic data from a random sample of patients identified from community
      echocardiographic laboratories, patients with moderate or severe LV dysfunction
      (ejection fraction < 35%) were linked to administrative databases to characterize
      baseline mortality risk (median follow-up duration of 4.85 years). Relative
      efficacy was ascertained from meta-analysis and clinical trial data. The baseline
      annual risk of arrhythmic death required for prophylactic ICDs to result in
      clinically meaningful survival benefits in the population was estimated at
      different ranges of relative efficacy and numbers needed to treat (NNTs)
      thresholds. RESULTS: LV dysfunction was a significant independent predictor of
      adverse outcomes. In total, 35.4% of the patients with moderate to severe LV
      dysfunction died during the follow-up period. Assuming a base-case relative
      efficacy of 66%, we estimated that the baseline risk for arrhythmic death
      required to exert a clinically meaningful NNT threshold of 50 in order to prevent
      one death (from any cause) was 3% per year or higher. CONCLUSIONS: The survival
      impact and cost-effectiveness of prophylactic ICDs in the population will depend
      upon the ability to risk-stratify and identify patients whose baseline risk for
      sudden cardiac death exceed 3% per year.

PMID- 16579829
TI  - Compliance to surgical and radiation treatment guidelines in relation to patient
      outcome in early stage endometrial cancer.
AB  - RATIONALE, AIMS AND OBJECTIVES: We evaluated the adherence to treatment
      guidelines in early stage endometrial cancer and the influence of adherence to
      guidelines on overall survival. METHOD: Patients were identified in the central
      region in the Netherlands from 1990 till 1995. Patient and tumour
      characteristics, surgical findings, radiation and follow-up data were abstracted
      from medical records. Endpoint was overall survival. Kaplan-Meier method was used
      to perform time-to-event analysis. Hazard ratios for overall survival were
      estimated with a Cox Proportional Hazards model. RESULTS: 359 patients were
      eligible for analysis. 335 patients presented with a clinical stage I cancer. 333
      patients underwent a Total Abdominal Hysterectomy with Bilateral Salpingo
      Oophorectomy (TAH/BSO), of which 301 were staged as International Federation of
      Gynaecology and Obstetrics (FIGO) stage I, whereas 34 (10.2%) as FIGO stage II.
      Of the 24 patients with a clinical stage II cancer, 12 underwent a Radical
      Hysterectomy with Pelvic Lymph Node Dissection (RH/PLND), of which seven were
      diagnosed with FIGO stage II. In 72.1% of the patients adjuvant radiation was
      given or not in adherence to the guidelines. Whether treatment was given
      according to the guidelines or not did not affect 5 years overall survival.
      CONCLUSION: This suggests that extensive surgical procedures are redundant in the
      treatment of occult stage II endometrial cancer.

PMID- 16579830
TI  - Evaluation of a national quality use of medicines service in Australia: an
      evolving model.
AB  - RATIONALE: To describe the first phase of a global evaluation framework for the
      National Prescribing Service (NPS), with a focus on services for health
      professionals, and in particular highlight the lessons learnt from evaluation
      around the establishment and implementation of this national program. METHODS:
      The agreed evaluation framework used mixed methods focused around a series of
      evaluation questions, aimed at measuring the overall effect of this new
      organization as well as the individual programs within it. The evaluation
      questions were determined a priori and were based on the objectives established
      by the organization in its first year of operation. A detailed analyses has been
      completed of: the process, scope and reach of program delivery using both
      quantitative and qualitative measures; changes in attitudes and knowledge
      measured through key informant interviews and surveys of professional groups and
      consumers; and changes in prescribing behaviour and savings to the Pharmaceutical
      Benefits Scheme (PBS) through analysis of prescription data. The evaluation
      period for this report was mid-1998 to mid-2004. RESULTS: The NPS has
      successfully implemented a complex, multi-faceted program across Australia. From
      1998 to 2004, in addition to print material provided to all general practitioners
      (GPs) and pharmacists, 90% of all GPs have been actively involved in one or more
      educational activity; 116 of 120 divisions of general practice have coordinated
      local NPS programs; and 9% of pharmacists have actively participated in at least
      one educational activity. Sixty per cent of GPs and pharmacists rated the printed
      educational materials as good or very good. In the last three years, the NPS
      activities have generated savings in the range of $121-163 million to the PBS,
      owing to changes in prescribing practices. CONCLUSION: The national evaluation
      framework has informed program delivery and ongoing design and development.
      Continued refinement of existing evaluation methods and further exploration of
      new techniques will remain a priority for the organization.

PMID- 16579832
TI  - Closing the gap: collaborative learning as a strategy to embed evidence within
      occupational therapy practice.
AB  - RATIONALE: The principles of clinical governance apply as guidelines for good
      practice to all practitioners. However, evidence-based practice (EBP) is proving
      a challenge for practitioners who lack the confidence to consume published
      research. For therapists not wishing to undertake formal study there is a risk of
      becoming disempowered within a culture of EBP. Opportunities to develop skills in
      consuming research have focused on the information dissemination model that has
      limited effect. Mutual reflective learning processes are recommended to empower
      practitioners to bridge the theory-practice gap. AIM: An action research approach
      investigated practice based collaborative learning as a catalyst to increase
      therapist's competence and confidence in consuming research and to explore the
      transition toward EB practitioner. METHOD AND RESULTS: A diagnostic survey
      reaffirmed therapist's lack of confidence in EBP. Formative interviews (n = 5)
      found an over reliance on professional craft and personal knowledge. Research
      knowledge was not included in participants' construct of a good practitioner and
      engagement in higher order critical reflection was limited. Collaborative
      learning groups (n = 6) embedded in practice integrated research, theory,
      practice and critical reflection. Supported by the collegial learning
      environment, a learning package developed participants' confidence and competence
      in consuming published research. Summative interviews (n = 5) evaluated the group
      and found that therapists were empowered to incorporate propositional knowledge
      into their clinical reasoning, engage in critical reflection and challenge their
      practice. They felt confident to incorporate EBP into their continuing
      professional development plans. Sustainability of these changes requires
      commitment from the therapists and the workplace.

PMID- 16579831
TI  - Professional approaches to stroke treatment in Japan: a relationship-centred
      model.
AB  - RATIONALE: To examine how stroke professionals in Japan approach rehabilitation
      therapy. METHODS: This qualitative study was based on Grounded Theory. Data
      collection included (1) non-participatory observation, (2) non-structured
      interviews, and (3) semi-structured interviews. A national hospital located in an
      urban area of the prefecture of Kanagawa in Japan specializing in the treatment
      of stroke and other neurological disorders. Stroke professionals (doctors,
      nurses, clinical psychologists, physiotherapists, occupational therapists and
      speech therapists), patients and patients' families. RESULTS: (1) Professionals
      recognized patient motivation as a factor related to rehabilitation outcome, but
      believed it to be a direct product of fostered fiduciary relationships and
      effective patient interaction. (2) Professionals regarded fiduciary relationships
      as the most important determinant of rehabilitation outcome. (3) Professionals
      adapted their behaviour and communication style in aims of fostering fiduciary
      relationships. These findings informed a three-component model of care: the
      Relationship-centred Model. CONCLUSIONS: The Relationship-centred Model describes
      how stroke professionals in Japan approach rehabilitative therapy. This model of
      care may be preferred by patients in other countries who also favour a family
      centred approach to decision making.

PMID- 16579833
TI  - Proliferation and apoptosis of hippocampal granule cells require local oestrogen
      synthesis.
AB  - Ovarian oestrogens have been demonstrated to influence neurogenesis in the
      dentate gyrus. As considerable amounts of oestrogens are synthesized in
      hippocampal neurones, we focused on the role of hippocampus-derived estradiol on
      proliferation and apoptosis of granule cells in vitro. We used hippocampal
      dispersion cultures, which allowed for cultivation of the cells under steroid-
      and serum-free conditions and monitoring of oestrogen synthesis. To address the
      influence of hippocampus-derived estradiol on neurogenesis, we inhibited
      oestrogen synthesis by treatment of hippocampal cell cultures with letrozole, a
      specific aromatase inhibitor. Alternatively, we used siRNA against steroidogenic
      acute regulatory protein (StAR). The number of proliferative cells decreased
      whereas the number of apoptotic cells increased dose-dependently, in response to
      reduced estradiol release into the medium after treatment with letrozole. This
      also held true for siRNA against StAR transfected cell cultures. Application of
      estradiol to the medium had no effect on proliferation and apoptosis whereas the
      anti-proliferative and pro-apoptotic effects of StAR knock-down and letrozole
      treatment were restored by treatment of the cultures with estradiol. Our findings
      suggest that neurogenesis and apoptosis in the hippocampus require a defined
      range of estradiol concentrations that is physiologically provided by hippocampal
      cells but not by gonads.

PMID- 16579834
TI  - Microdialysis measures of functional increases in ACh release in the hippocampus
      with and without inclusion of acetylcholinesterase inhibitors in the perfusate.
AB  - Because brain extracellular acetylcholine (ACh) levels are near detection limits
      in microdialysis samples, an acetylcholinesterase (AChE) inhibitor such as
      neostigmine is often added to microdialysis perfusates to increase ACh levels in
      the dialysate, a practice that raises concerns that the inhibitor might alter the
      results. Two experiments compared functional differences in ACh release with and
      without neostigmine. In the first experiment, 30-60% increases in extracellular
      ACh concentrations in the hippocampus were evident during food-rewarded T-maze
      training with 20-500 nm neostigmine in the perfusate but no increases were seen
      without neostigmine. In the second experiment, 78% increases in ACh release in
      the hippocampus were seen after injections of the GABA(A) receptor antagonist,
      bicuculline, into medial septum only if neostigmine (50 nm) was included in the
      perfusate. These findings suggest that, in the hippocampus, endogenous brain
      AChEs are very efficient at removing extracellular ACh, obscuring differences in
      ACh release in these experiments. Therefore, inclusion of AChE inhibitors in the
      microdialysis perfusate may be necessary under some conditions for observations
      of functional changes in release of ACh in the hippocampus.

PMID- 16579835
TI  - Problem of distinguishing false-positive tests from acute or transient
      Helicobacter pylori infections.
AB  - BACKGROUND: Reliable detection of acute Helicobacter pylori infections remains
      problematic. The high prevalence of false-positive non-invasive tests in low H.
      pylori prevalence populations makes identification of acute and transient
      infections difficult. METHODS: We explored the use of serum pepsinogens (PG) for
      diagnosis of acute infection in patients following H. pylori challenge such that
      the onset of the infection was known. We then compared those findings to a group
      of children with presumed acute infections defined as a positive urea breath test
      (UBT) and negative IgG serology. RESULTS: We examined the pattern and calculated
      cut-off values of PG levels in 18 adult volunteers with known acute H. pylori
      infection. We then compared the results with sera from nine symptomatic children
      with presumed acute H. pylori infection and a matched control group of nine
      children who did not meet criteria for acute H. pylori infection. In acute
      infection, both PGI and II levels increased following H. pylori infection
      reaching a peak by 2 weeks post-infection. The frequency of a positive test
      defined as a value > mean +2 SD was 17, 71, and 94% at week 1, 2, and 4 post
      infection, respectively. Only one child with presumed acute H. pylori infection
      had an elevated serum PGI and one had an elevated PGII. Five of the children had
      follow-up UBTs and four were negative consistent with the diagnosis of false
      positive UBT. H. pylori infection was confirmed in the child with an elevated PGI
      level. CONCLUSIONS: These data suggest that a single positive noninvasive test in
      populations of low prevalence is most likely a false-positive result. This
      suggests that a single positive test requires confirmation preferably using a
      test that measures a different parameter (e.g., UBT confirmed by stool antigen
      test). It appears that most "transient"H. pylori infections are diagnosed on the
      basis of false-positive tests. PG levels are possible candidates as the
      confirmatory test.

PMID- 16579836
TI  - Helicobacter pylori infection and colorectal cancer risk: a meta-analysis.
AB  - BACKGROUND: Several studies suggested an association between Helicobacter pylori
      infection and colorectal carcinoma or adenoma risk. However, different authors
      reported quite varying estimates. We carried out a systematic review and meta
      analysis of published studies investigating this association and paid special
      attention to the possibility of publication bias and sources of heterogeneity
      between studies. MATERIALS AND METHODS: An extensive literature search and cross
      referencing were performed to identify all published studies. Summary estimates
      were obtained using random-effects models. The presence of possible publication
      bias was assessed using different statistical approaches. RESULTS: In a meta
      analysis of the 11 identified human studies, published between 1991 and 2002, a
      summary odds ratio of 1.4 (95% CI, 1.1-1.8) was estimated for the association
      between H. pylori infection and colorectal cancer risk. The graphical funnel plot
      appeared asymmetrical, but the formal statistical evaluations did not provide
      strong evidence of publication bias. The proportion of variation of study results
      because of heterogeneity was small (36.5%). CONCLUSIONS: The results of our meta
      analysis are consistent with a possible small increase in risk of colorectal
      cancer because of H. pylori infection. However, the possibility of some
      publication bias cannot be ruled out, although it could not be statistically
      confirmed. Larger, better designed and better controlled studies are needed to
      clarify the situation.

PMID- 16579837
TI  - Prevalence of Helicobacter pylori in Georgian patients with dyspepsia.
AB  - BACKGROUND: Georgia has showed a high prevalence of peptic ulcer disease (PUD),
      but the prevalence of Helicobacter pylori in this country is practically unknown.
      The purpose of this study was to determine the prevalence of H. pylori and
      specific genotypes in different populations in Georgia. MATERIALS AND METHODS: We
      studied 62 patients from several hospitals in Tbilisi, Georgia. More than 55% of
      patients had PUD. We determined H. pylori presence as well as specific genotypes
      cagA and vacA by polymerase chain reaction. In addition, we studied serum samples
      from 94 healthy persons to determine H. pylori and CagA prevalence by ELISA.
      RESULTS: We found a high prevalence of H. pylori and CagA in the healthy
      population (70.2 and 57.4%, respectively) and a high prevalence of CagA among the
      H. pylori-positive persons (71.2%). Prevalence increased with age as reported in
      other countries (p = .05). Among symptomatic persons, we found nearly the same
      high prevalence of H. pylori (64.5%) as in the asymptomatic population.
      Furthermore, in symptomatic H. pylori patients, we found 65.0 and 67.5%
      prevalence of cagA and vacA, respectively. For 33 patients with PUD, 24 patients
      (72.7%) were H. pylori positive and 66.7% of them were cagA positive. In
      contrast, among the patients with non-ulcer dyspepsia (NUD), 16 (55.2%) were H.
      pylori positive and 62.5% of them were colonized with cagA-positive strains. H.
      pylori and cagA prevalence were not significantly different between PUD and
      patients with NUD. CONCLUSIONS: We confirmed that among individuals in Georgia,
      the prevalence of H. pylori is high and cagA-positive strains were equally
      present among H. pylori-positive patients with PUD and NUD and asymptomatic
      persons.

PMID- 16579838
TI  - Comparison of localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma
      with and without Helicobacter pylori infection.
AB  - BACKGROUND: The clinical features and clinical course of Helicobacter pylori
      negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma are unclear
      and a treatment strategy has not yet been established. AIM: To clarify the
      clinical differences between H. pylori-positive and H. pylori-negative gastric
      MALT lymphoma, we compared these two types of gastric MALT lymphoma. MATERIALS
      AND METHODS: Fifty-seven patients with localized gastric MALT lymphoma were
      studied. H. pylori infection was present in 41 and absent in 16. Treatment
      consisted of antibiotic therapy and/or 30 Gy radiation therapy. Response
      assessment was performed every 3-6 months by esophagogastroduodenoscopy including
      gathering biopsy samples, endoscopic ultrasonography, clinical examination, and
      various imaging procedures. The median follow-up period was 37 months. RESULTS:
      There were no significant differences between H. pylori-positive and H. pylori
      negative gastric MALT lymphoma patients in terms of sex, age, stage, gross
      phenotype, affected area of the stomach, or the presence of monoclonality.
      Complete regression was achieved with antibiotic therapy against H. pylori
      negative gastric MALT lymphoma in one of nine patients (11.1%), compared to 28 of
      38 patients (73.7%) with H. pylori-positive gastric MALT lymphoma (p < .001).
      Radiation therapy showed high effectiveness for the local control of H. pylori
      negative or antibiotic-resistant gastric MALT lymphoma (92.9%), although distant
      recurrence was recognized in three of 14 patients (21.4%). Two of 16 patients
      (12.5%) with H. pylori-negative gastric MALT lymphoma died because of the
      transformation of the disease into diffuse large B-cell lymphoma. There was a
      significant difference in both the overall and cause-specific survival rate
      between the two groups (p = .038). CONCLUSION: Radiation therapy is the effective
      treatment for H. pylori-negative or antibiotic-resistant localized gastric MALT
      lymphoma. However, careful systemic follow-up for distant involvement should be
      required. Transformation into diffuse large B-cell lymphoma is thought to be the
      important cause of death in patients with gastric MALT lymphoma.

PMID- 16579839
TI  - The mechanism of heat-shock protein 70 gene expression abolition in gastric
      epithelium caused by Helicobacter pylori infection.
AB  - BACKGROUND: The members of the family of heat shock factors coordinate the
      inducible transcription of heat shock genes in response to diverse stimuli. Any
      disturbances in signal transduction may lead to the attenuation of heat shock
      proteins synthesis and to cell death due to apoptosis. It has been shown by
      others that different nuclear factors, such as nuclear factor interleukin 6 or
      signal transducer and activator of transcription 3, co-operate with heat shock
      factors, mostly enhancing their activator effect on heat shock proteins genes
      expression. Therefore, we sought to determine whether apoptosis induced in the
      gastric epithelium exposed to live Helicobacter pylori might occur due to the
      elimination of HSP70 expression and deregulation of the heat shock response of
      the cell. MATERIALS AND METHODS: Experiments were performed on KATO III gastric
      epithelial cells exposed to live cagA, vacA expressing Hp over different periods
      of time. Total cellular RNA, cytoplasmic and nuclear proteins were isolated for
      polymerase chain reaction, western-blot, electrophoretic mobility shift assay,
      decoy and co-immunoprecipitation studies. RESULTS: We found that in human gastric
      epithelium exposed to Helicobacter pylori, heat shock factor 1 is bound and
      restrained in complexes by phosphorylated signal transducer and activator of
      transcription 3 protein. In consequence, heat shock factor 1 bound up with
      phosphorylated signal transducer and activator of transcription 3 protein is
      unable to activate HSP70 protein synthesis in KATO III cells under stress
      conditions. Helicobacter pylori also causes changes in bax/bcl-2 cellular
      equilibrium, leading to the induction of apoptosis. CONCLUSIONS: The observed
      phenomenon might be the mechanism whereby gastric epithelium adapts to the
      infection of Helicobacter pylori, eliminating cells which are damaged or altered
      by bacterial cytotoxic products from the tissue.

PMID- 16579840
TI  - The effects of genetic polymorphisms of IL-1 and TNF-A on Helicobacter pylori
      induced gastroduodenal diseases in Korea.
AB  - OBJECTIVE: To evaluate whether or not genetic polymorphism of IL-1B, IL-1RN, and
      TNF-Alpha is an important factor in the different expression of gastroduodenal
      diseases after Helicobacter pylori infection. METHODS: This study consisted of
      1360 subjects: control, gastric cancer (GC, intestinal type, and diffuse type),
      benign gastric ulcer (BGU), duodenal ulcer, and first-degree gastric cancer
      relative (GCR). IL-1Beta-511 and TNF-A-308 biallelic polymorphism were genotyped
      by 5' nuclease polymerase chain reaction (PCR) assays, and PCR-restriction
      fragment length polymorphism (PCR-RFLP). IL-1RN penta-allelic variable number of
      tandem repeats was genotyped by PCR. RESULTS: There was no difference in the
      genetic polymorphism of IL-1Beta-511, IL-1RN and TNF-A in the patients with
      gastric cancer regardless of H. pylori positivity compared with control. However,
      the frequencies of IL-1B-511 C/T (OR: 0.5, 95% CI: 0.3-0.7) and T carrier (OR:
      0.6, 95% CI: 0.4-0.8) were lower in the H. pylori-positive BGU patients. The IL
      1RN 2/2 was higher (OR: 5.5, 95% CI: 1.1-28.5) in the H. pylori-positive GCR.
      There was no significance in the polymorphism of TNF-Alpha-308 regardless of H.
      pylori-induced gastroduodenal diseases. CONCLUSIONS: The IL-1Beta-511 T-carrier
      polymorphism has a negative effect on the development of H. pylori-positive BGU,
      and high frequency of IL-1RN 2/2 was found in the H. pylori-positive relatives of
      GC patients, which suggest that this genetic polymorphism could play some role in
      the H. pylori-induced gastroduodenal diseases in Korea.

PMID- 16579842
TI  - Effects of estradiol and progesterone on gastric mucosal response to early
      Helicobacter pylori infection in female gerbils.
AB  - BACKGROUND: Gender differences have been shown regarding the changes in the
      inflammatory response, gastrin secretion, and gastric acidity during Helicobacter
      pylori infection. AIM: To investigate the role of estradiol and progesterone in
      the changes of the gastric mucosa induced by H. pylori during the early stage of
      infection in female gerbils. MATERIALS AND METHODS: Thirty-three adult
      ovariectomized female gerbils were infected with H. pylori (SS1); 7 days after
      infection they were treated with low and high doses of estradiol (50 and 250
      microg/60 days pellet), progesterone (15 and 50 mg/60 days pellet) and vehicle.
      Non-ovariectomized infected gerbils were used as control. Gerbils were euthanized
      after 6 weeks of infection. Histologic evaluation, immunohistochemical detection
      of proliferation cell nuclear antigen (PCNA), gastrin, and apoptosis by terminal
      deoxynucleotide nick end labeling (TUNEL) assay were performed. Positive cells
      for PCNA, TUNEL, and gastrin were counted in 10 oriented glands per animal. Two
      sided p = .05 was considered significant. RESULTS: Estradiol-treated groups
      showed more intense and extended acute and follicular gastritis compared to the
      vehicle group, whereas progesterone-treated groups presented less gastritis than
      the other groups. Proliferation and apoptosis indexes were significantly lower in
      the vehicle group when compared with those of the control; both indexes were
      increased in the high-dose estradiol and progesterone groups as compared with
      those of the vehicle. Grade I nonmetaplastic atrophy was observed in the vehicle
      and progesterone groups. The high-dose progesterone group showed a significant
      reduction in the number of gastrin cells. CONCLUSIONS: Estradiol and progesterone
      participate in the gastric mucosal response to early H. pylori infection in
      gerbils.

PMID- 16579843
TI  - Avoiding errors in the identification and 16S rRNA sequencing data of members of
      the Helicobacteriaceae family detected in clinical samples.

PMID- 16579841
TI  - Mucosal immunization with a urease B DNA vaccine induces innate and cellular
      immune responses against Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori is recognized as a major risk factor for
      recurrent gastroduodenal inflammatory diseases and gastric adenocarcinoma. The
      high prevalence of H. pylori infection worldwide, the risks of side-effects from
      antibiotic therapy, and increasing resistance to antibiotics are the main primers
      for the development of improved H. pylori vaccines. The antigenic potential of
      its urease enzyme, a critical virulence factor required for colonization of the
      gastric mucosa, has been demonstrated in animal and human studies. An important
      but controversial issue in H. pylori vaccine studies is the type of immune
      response required to control infection. A new approach in H. pylori vaccinology
      is the administration of DNA vaccines, which has included heat-shock protein and
      catalase DNA vaccines. MATERIALS AND METHODS: The H. pylori urease subunit B
      construct or vector alone was administered to mice via the intranasal route.
      Spleens and stomachs were examined on day 0 and weeks 3, 6, and 12 after
      immunization. Proliferation of spleen cells was assessed using the
      carboxyfluorescein diacetate succinimidyl ester-based flow cytometry assay and
      cytokine secretion from cultured spleen cells was detected by ELISA, after
      stimulation with the urease subunit B recombinant antigen. Total RNA was isolated
      from stomach and spleen tissue and the expression of beta-defensin and cytokine
      genes was monitored by reverse transcription followed by polymerase chain
      reaction (RT-PCR). Immunized mice were challenged with H. pylori and bacterial
      DNA quantified by TaqMan PCR. RESULTS: The urease B subunit DNA vaccine increased
      INF-gamma secretion and splenocyte proliferation without inducing adverse effects
      in the spleen. Increase in gastric beta-defensin 1 and marked induction in local
      IL-10 : IFN-gamma ratio up to 12 weeks post-immunization suggest a potential role
      for local innate immune responses in protection at the site of infection.
      Although significant bacterial reduction in the stomachs of urease B subunit DNA
      immunized mice was observed, intermediate reduction was also noted in the vector
      group. Increased defensin expression and adjuvant effects of the cytosine
      preceding guanosine motifs may contribute to this phenomenon. Our data confirm
      that cytosine preceding guanosine motifs, even without coadministration with
      antigen, can reduce extracellular bacterial load. CONCLUSIONS: In this study, a
      DNA construct encoding the urease B subunit was assessed for its immune profile
      and its ability to reduce bacterial colonization in the murine stomach. Our
      studies suggest that local innate immune responses may play a greater role than
      previously supposed in limiting H. pylori colonization in the gastric mucosa.

PMID- 16579844
TI  - The role of Amazonian herbal medicine Sangre de Grado in Helicobacter pylori
      infection and its association with metallothionein expression.

PMID- 16579845
TI  - Response to "eradication of Helicobacter pylori and resolution of gastritis in
      the gastric mucosa of IL-10-deficient mice".

PMID- 16579846
TI  - Dieting practices, weight perceptions, and body composition: a comparison of
      normal weight, overweight, and obese college females.
AB  - BACKGROUND: Of concern to health educators is the suggestion that college females
      practice diet and health behaviors that contradict the 2005 dietary guidelines
      for Americans. In this regard, there remain gaps in the research related to
      dieting among college females. Namely, do normal weight individuals diet
      differently from those who are overweight or obese, and are there dieting
      practices used by females that can be adapted to promote a healthy body weight?
      Since it is well recognized that females diet, this study seeks to determine the
      dieting practices used among normal, overweight, and obese college females (do
      they diet differently) and identify dieting practices that could be pursued to
      help these females more appropriately achieve and maintain a healthy body weight.
      METHODS: A total of 185 female college students aged 18 to 24 years participated
      in this study. Height, weight, waist and hip circumferences, and skinfold
      thickness were measured to assess body composition. Surveys included a dieting
      practices questionnaire and a 30-day physical activity recall. Participants were
      classified according to body mass index (BMI) as normal weight (n = 113),
      overweight (n = 35), or obese (n = 21). Data were analyzed using JMP IN(R)
      software. Descriptive statistics included means, standard deviations, and
      frequency. Subsequent data analysis involved Pearson X2 and one-way analysis of
      variance with comparison for all pairs that were significantly different using
      Tukey-Kramer honestly significant difference test. RESULTS: Outcomes of this
      study indicate the majority of participants (83%) used dieting for weight loss
      and believed they would be 2% to 6% greater than current weight if they did not
      diet; normal weight, overweight, and obese groups perceived attractive weight to
      be 94%, 85%, and 74%, respectively, of current weight; 80% of participants
      reported using physical activity to control weight, although only 19% exercised
      at a level that would promote weight loss; only two of 15 dieting behaviors
      assessed differed in terms of prevalence of use among groups, which were
      consciously eating less than you want (44% normal weight, 57% overweight, 81%
      obese) and using artificial sweeteners (31% normal weight and overweight, 5%
      obese); and the most prevalent explicit maladaptive weight loss behavior was
      smoking cigarettes (used by 9% of participants) and most unhealthy was skipping
      breakfast (32%). CONCLUSION: Collectively, results indicate female college
      students, regardless of weight status, would benefit from open discussions with
      health educators regarding healthy and effective dieting practices to
      achieve/maintain a healthy body weight. The results are subject to replication
      among high school, middle-aged, and older females.

PMID- 16579847
TI  - Interleukin-10 haplotypes in Celiac Disease in the Spanish population.
AB  - BACKGROUND: Celiac disease (CD) is a chronic disorder characterized by a
      pathological inflammatory response after exposure to gluten in genetically
      susceptible individuals. The HLA complex accounts for less than half of the
      genetic component of the disease, and additional genes must be implicated.
      Interleukin-10 (IL-10) is an important regulator of mucosal immunity, and several
      reports have described alterations of IL-10 levels in celiac patients. The IL-10
      gene is located on chromosome 1, and its promoter carries several single
      nucleotide polymorphisms (SNPs) and microsatellites which have been associated to
      production levels. Our aim was to study the role of those polymorphisms in
      susceptibility to CD in our population. METHODS: A case-control and a familial
      study were performed. Positions -1082, -819 and -592 of the IL-10 promoter were
      typed by TaqMan and allele specific PCR. IL10R and IL10G microsatellites were
      amplified with labelled primers, and they were subsequently run on an automatic
      sequencer. In this study 446 patients and 573 controls were included, all of them
      white Spaniards. Extended haplotypes encompassing microsatellites and SNPs were
      obtained in families and estimated in controls by the Expectation-Maximization
      algorithm. RESULTS: No significant associations after Bonferroni correction were
      observed in the SNPs or any of the microsatellites. Stratification by HLA-DQ2
      (DQA1*0501-DQB1*02) status did not alter the results. When extended haplotypes
      were analyzed, no differences were apparent either. CONCLUSION: The IL-10
      polymorphisms studied are not associated with celiac disease. Our data suggest
      that the IL-10 alteration seen in patients may be more consequence than cause of
      the disease.

PMID- 16579848
TI  - Moderate hypoxia influences excitability and blocks dendrotoxin sensitive K+
      currents in rat primary sensory neurones.
AB  - Hypoxia alters neuronal function and can lead to neuronal injury or death
      especially in the central nervous system. But little is known about the effects
      of hypoxia in neurones of the peripheral nervous system (PNS), which survive
      longer hypoxic periods. Additionally, people have experienced unpleasant
      sensations during ischemia which are dedicated to changes in conduction
      properties or changes in excitability in the PNS. However, the underlying ionic
      conductances in dorsal root ganglion (DRG) neurones have not been investigated in
      detail. Therefore we investigated the influence of moderate hypoxia (27.0 +/- 1.5
      mmHg) on action potentials, excitability and ionic conductances of small neurones
      in a slice preparation of DRGs of young rats. The neurones responded within a few
      minutes non-uniformly to moderate hypoxia: changes of excitability could be
      assigned to decreased outward currents in most of the neurones (77%) whereas a
      smaller group (23%) displayed increased outward currents in Ringer solution. We
      were able to attribute most of the reduction in outward-current to a voltage
      gated K+ current which activated at potentials positive to -50 mV and was
      sensitive to 50 nM alpha-dendrotoxin (DTX). Other toxins that inhibit subtypes of
      voltage gated K+ channels, such as margatoxin (MgTX), dendrotoxin-K (DTX-K), r
      tityustoxin Kalpha (TsTX-K) and r-agitoxin (AgTX-2) failed to prevent the hypoxia
      induced reduction. Therefore we could not assign the hypoxia sensitive K+ current
      to one homomeric KV channel type in sensory neurones. Functionally this K+
      current blockade might underlie the increased action potential (AP) duration in
      these neurones. Altogether these results, might explain the functional impairment
      of peripheral neurones under moderate hypoxia.

PMID- 16579849
TI  - Production and characterization of murine models of classic and intermediate
      maple syrup urine disease.
AB  - BACKGROUND: Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism
      caused by a deficiency of branched-chain keto acid dehydrogenase. MSUD has
      several clinical phenotypes depending on the degree of enzyme deficiency. Current
      treatments are not satisfactory and require new approaches to combat this
      disease. A major hurdle in developing new treatments has been the lack of a
      suitable animal model. METHODS: To create a murine model of classic MSUD, we used
      gene targeting and embryonic stem cell technologies to create a mouse line that
      lacked a functional E2 subunit gene of branched-chain keto acid dehydrogenase. To
      create a murine model of intermediate MSUD, we used transgenic technology to
      express a human E2 cDNA on the knockout background. Mice of both models were
      characterized at the molecular, biochemical, and whole animal levels. RESULTS: By
      disrupting the E2 subunit gene of branched-chain keto acid dehydrogenase, we
      created a gene knockout mouse model of classic MSUD. The homozygous knockout mice
      lacked branched-chain keto acid dehydrogenase activity, E2 immunoreactivity, and
      had a 3-fold increase in circulating branched-chain amino acids. These metabolic
      derangements resulted in neonatal lethality. Transgenic expression of a human E2
      cDNA in the liver of the E2 knockout animals produced a model of intermediate
      MSUD. Branched-chain keto acid dehydrogenase activity was 5-6% of normal and was
      sufficient to allow survival, but was insufficient to normalize circulating
      branched-chain amino acids levels, which were intermediate between wildtype and
      the classic MSUD mouse model. CONCLUSION: These mice represent important animal
      models that closely approximate the phenotype of humans with the classic and
      intermediate forms of MSUD. These animals provide useful models to further
      characterize the pathogenesis of MSUD, as well as models to test novel
      therapeutic strategies, such as gene and cellular therapies, to treat this
      devastating metabolic disease.

PMID- 16579850
TI  - Reliability of measures of impairments associated with patellofemoral pain
      syndrome.
AB  - BACKGROUND: The reliability and measurement error of several impairment measures
      used during the clinical examination of patients with patellofemoral pain
      syndrome (PFPS) has not been established. The purpose was to determine the inter
      tester reliability and measurement error of measures of impairments associated
      with PFPS in patients with PFPS. METHODS: A single group repeated measures design
      was used. Two pairs of physical therapists participated in data collection.
      Examiners were blinded to each others' measurements. RESULTS: Thirty patients
      (age 29 +/- 8; 17 female) with PFPS participated in this study. Inter-tester
      reliability coefficients were substantial for measures of hamstrings, quadriceps,
      plantarflexors, and ITB/TFL complex length, hip abductors strength, and foot
      pronation (ICCs from .85 to .97); moderate for measures of Q-angle, tibial
      torsion, hip external rotation strength, lateral retinacular tightness, and
      quality of movement during a step down task (ICCs from .67 to .79); and poor for
      femoral anteversion (ICC of .45). Standard error of measurement (SEM) for
      measures of muscle length ranged from 1.6 degrees to 4.3 degrees. SEM for Q
      angle, tibial torsion, and femoral anteversion were 2.4 degrees, 2.9 degrees, and
      4.5 degrees respectively. SEM for foot pronation was 1 mm. SEM for measures of
      muscle strength was 1.8 Kg for abduction and 2.4 Kg for external rotation.
      CONCLUSION: Several of the impairments associated with PFPS had sufficient
      reliability and low measurement error. Further investigation is needed to test if
      these impairment measurements are related to physical function and whether or not
      they are useful for decision-making.

PMID- 16579852
TI  - Comparative validation of the IPAQ and the 7-Day PAR among women diagnosed with
      breast cancer.
AB  - BACKGROUND: The criterion-related validity and measurement bias of the long form
      of the International Physical Activity Questionnaire (IPAQ) was compared to the 7
      Day Physical Activity Recall (PAR). METHODS: Participants were women who have
      been diagnosed with breast cancer and enrolled in the ongoing Women's Healthy
      Eating and Living Study. Women (N = 159, average age 57 years) wore an
      accelerometer for one week and then completed the IPAQ or the PAR. RESULTS: The
      validity correlation of the PAR was significantly higher (p < 0.001) than the
      IPAQ (0.73 vs. 0.33, respectively). The PAR and IPAQ overestimated total physical
      activity by 13% vs. 247%, respectively. The PAR had better sensitivity (p = 0.14)
      and specificity (p < .01) than the IPAQ (100% vs. 71% and 84% vs. 59%,
      respectively) in predicting attainment of the ACSM physical activity guideline.
      CONCLUSION: The PAR was superior to the IPAQ in terms of validity, measurement
      bias, and screening statistics.

PMID- 16579851
TI  - Quantitative prediction of mouse class I MHC peptide binding affinity using
      support vector machine regression (SVR) models.
AB  - BACKGROUND: The binding between peptide epitopes and major histocompatibility
      complex proteins (MHCs) is an important event in the cellular immune response.
      Accurate prediction of the binding between short peptides and the MHC molecules
      has long been a principal challenge for immunoinformatics. Recently, the modeling
      of MHC-peptide binding has come to emphasize quantitative predictions: instead of
      categorizing peptides as "binders" or "non-binders" or as "strong binders" and
      "weak binders", recent methods seek to make predictions about precise binding
      affinities. RESULTS: We developed a quantitative support vector machine
      regression (SVR) approach, called SVRMHC, to model peptide-MHC binding
      affinities. As a non-linear method, SVRMHC was able to generate models that out
      performed existing linear models, such as the "additive method". By adopting a
      new "11-factor encoding" scheme, SVRMHC takes into account similarities in the
      physicochemical properties of the amino acids constituting the input peptides.
      When applied to MHC-peptide binding data for three mouse class I MHC alleles, the
      SVRMHC models produced more accurate predictions than those produced previously.
      Furthermore, comparisons based on Receiver Operating Characteristic (ROC)
      analysis indicated that SVRMHC was able to out-perform several prominent methods
      in identifying strongly binding peptides. CONCLUSION: As a method with
      demonstrated performance in the quantitative modeling of MHC-peptide binding and
      in identifying strong binders, SVRMHC is a promising immunoinformatics tool with
      not inconsiderable future potential.

PMID- 16579853
TI  - Cognitive, emotional, and quality of life outcomes in patients with pulmonary
      arterial hypertension.
AB  - BACKGROUND: The effects of pulmonary arterial hypertension on cardiovascular and
      physical function are well documented. Limited information exists regarding the
      effects of pulmonary arterial hypertension on cognitive function despite patient
      reports of problems with memory and attention. Our primary purpose was to
      determine if a prospectively identified cohort of pulmonary arterial hypertension
      patients had cognitive sequelae. Our secondary purpose was to determine the
      relationships between cognitive sequelae and neuropsychological test scores with
      depression, anxiety, and quality of life. METHODS: Forty-six adults with
      pulmonary arterial hypertension underwent assessment of cognitive function,
      depression, anxiety, and quality of life using standardized neuropsychological
      tests and questionnaires. The patients' scores were compared to normal population
      data. Medical, affective, neuropsychological, and quality of life data for
      patients with and without cognitive sequelae were compared using analysis of
      variance, Chi-square, or Fisher exact tests for categorical data. Correlations
      assessed relationships between neuropsychological test scores, depression,
      anxiety, quality of life, and medical data. RESULTS: Cognitive sequelae occurred
      in 58% (27/46) of the pulmonary arterial hypertension patients. Patients with
      cognitive sequelae had worse verbal learning, delayed verbal memory, executive
      function, and fine motor scores compared to patients without cognitive sequelae.
      Twenty-six percent of patients had moderate to severe depression and 19% had
      moderate to severe anxiety. Depression, anxiety and quality of life were not
      different for patients with or without cognitive sequelae. Our patients had
      decreased quality of life, which was associated with worse working memory.
      CONCLUSION: Patients with pulmonary arterial hypertension have cognitive
      impairments, depression, anxiety, and decreased quality of life. Depression,
      anxiety, and quality of life were similar for patients with cognitive sequelae
      compared to those without cognitive sequelae. Decreased quality of life was
      associated with worse verbal and working memory. Clinicians should be aware of
      adverse brain related outcomes in PAH patients. Attention to proximal
      determinants and possible interventions to prevent or reduce cognitive and
      emotional morbidity and decreased quality of life are warranted and should be an
      emphasis in outcomes research.

PMID- 16579854
TI  - Decreased intracellular zinc in human tumorigenic prostate epithelial cells: a
      possible role in prostate cancer progression.
AB  - BACKGROUND: Zinc plays important roles in maintaining normal function of the
      prostate and in development of prostate malignancy. It has been demonstrated that
      prostate malignant epithelial cells contain much less cellular zinc than the
      surrounding normal epithelial cells. However, the pathway(s) which leads to lower
      zinc accumulation in malignant prostate epithelial cells is poorly understood. In
      this study, the zinc homeostatic features of two human prostate epithelial cell
      lines (non-tumorigenic, RWPE1, and tumorigenic, RWPE2) were investigated. Effects
      of over-expression of ZIP1 in RWPE2 on cell proliferation and apoptosis were also
      studied. RESULTS: RWPE2 accumulated less intracellular zinc than RWPE1 due to the
      decreased zinc uptake activity. The mRNA expression of ZIP1 and ZIP3 in RWPE1 and
      RWPE2 was comparable. However, the protein expression of ZIP1 in RWPE2 was lower
      than that in RWPE1. ZIP3 was detected in a lysosomal compartment of RWPE2 while
      no ZIP3 was detected in the same compartment of RWPE1. Over-expression of ZIP1 in
      RWPE2 resulted in an elevation of intracellular zinc concentration and
      suppression of cell growth of RWPE2 due to the increased apoptosis. CONCLUSION:
      These findings suggest that tumorigenic prostate epithelial cells accumulated
      less intracellular zinc than non-tumorigenic prostate epithelial cells. The
      reduction in capacity for accumulation of intracellular zinc in tumorigenic
      prostate epithelial cells may be caused by the decrease in the ZIP1 protein
      expression and the intracellular redistribution of ZIP3 in RWPE2. RWPE1 and RWPE2
      are excellent cellular models to study the association of intracellular zinc
      levels with prostate cancer progression.

PMID- 16579855
TI  - The Alberta Ambassador Program: delivering Health Technology Assessment results
      to rural practitioners.
AB  - BACKGROUND: The purpose of Health Technology Assessment (HTA) is to make the best
      possible summary of the evidence regarding specific health interventions in order
      to influence health care and policy decisions. The need for decision makers to
      find relevant HTA data when it is needed is a barrier to its usefulness. These
      barriers are highest in rural areas and amongst isolated practitioners. METHODS:
      A multidisciplinary team developed an interactive case-based instructional
      strategy on the topic of chronic non-cancer pain (CNCP) management using clinical
      evidence derived by HTA. The evidence for each of 18 CNCP interventions was
      distilled into single-sheet summaries. Clinicians and HTA specialists
      ('Ambassadors') conducted 11 two-hour interactive sessions on CNCP in eight of
      Alberta's nine health regions. Pre- and post-session evaluations were conducted.
      RESULTS: The sessions were attended by 130 individuals representing 14 health and
      administrative disciplines. The ambassador model was well received. The use of
      content experts as ambassadors was highly rated. The educational strategy was
      judged to be effective. Awareness of the best evidence in CNCP management was
      increased. Although some participants reported practice changes as a result of
      the workshops, the program was not designed to measure changes in patient
      outcome. CONCLUSION: The ambassador program was successful in increasing
      awareness of the best evidence in CNCP management, and positively influenced
      treatment decisions. Its teaching methods were felt to be unique and innovative
      by participants. Its methods could be applied to other clinical content areas in
      order to increase the uptake of the results of HTA.

PMID- 16579856
TI  - Latent tuberculosis in HIV positive, diagnosed by the M. tuberculosis specific
      interferon-gamma test.
AB  - BACKGROUND: Although tuberculosis (TB) is a minor problem in Denmark, severe and
      complicated cases occur in HIV positive. Since the new M. tuberculosis specific
      test for latent TB, the QuantiFERON-TB In-Tube test (QFT-IT) became available the
      patients in our clinic have been screened for the presence of latent TB using the
      QFT-IT test. We here report the results from the first patients screened.
      METHODS: On a routine basis the QFT-IT test was performed and the results from
      590 HIV positive individuals consecutively tested are presented here. CD4 cell
      count and TB risk-factors were recorded from patient files. MAIN FINDINGS:
      27/590(4.6%) of the individuals were QFT-IT test positive, indicating the
      presence of latent TB infection. Among QFT-IT positive patients, 78% had risk
      factors such as long-term residency in a TB high endemic area (OR:5.7), known TB
      exposure (OR:4.9) or previous TB disease (OR:4.9). The prevalence of latent TB in
      these groups were 13%, 16% and 19% respectively. There was a strong correlation
      between low CD4 T-cell count and a low mitogen response (P < 0.001;Spearman) and
      more patients with low CD4 cell count had indeterminate results. CONCLUSION: We
      found an overall prevalence of latent TB infection of 4.6% among the HIV positive
      individuals and a much higher prevalence of latent infection among those with a
      history of exposure (16%) and long term residency in a high endemic country
      (13%). The QFT-IT test may indeed be a useful test for HIV positive individuals,
      but in severely immunocompromised, the test may be impaired by T-cell anergy.

PMID- 16579857
TI  - Internship workplace preferences of final-year medical students at Zagreb
      University Medical School, Croatia: all roads lead to Zagreb.
AB  - BACKGROUND: Human resources management in health often encounters problems
      related to workforce geographical distribution. The aim of this study was to
      investigate the internship workplace preferences of final-year medical students
      and the reasons associated with their choices. METHOD: A total of 204 out of 240
      final-year medical students at Zagreb University Medical School, Croatia, were
      surveyed a few months before graduation. We collected data on each student's
      background, workplace preference, academic performance and emigration
      preferences. Logistic regression was used to analyse the factors underlying
      internship workplace preference, classified into two categories: Zagreb versus
      other areas. RESULTS: Only 39 respondents (19.1%) wanted to obtain internships
      outside Zagreb, the Croatian capital. Gender and age were not significantly
      associated with internship workplace preference. A single predictor variable
      significantly contributed to the logistic regression model: students who believed
      they would not get the desired specialty more often chose Zagreb as a preferred
      internship workplace (odds ratio 0.32, 95% CI 0.12-0.86). CONCLUSION: A strong
      preference for Zagreb as an internship workplace was recorded. Uncertainty about
      getting the desired specialty was associated with choosing Zagreb as a workplace,
      possibly due to more extensive and diverse job opportunities.

PMID- 16579858
TI  - Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors.
AB  - BACKGROUND: Mutations in the c-KIT proto-oncogene have been implicated in the
      progression of several neoplastic diseases, including gastrointestinal stromal
      tumors and mastocytosis in humans, and cutaneous mast cell tumors (MCTs) in
      canines. Mutations in human mastocytosis patients primarily occur in c-KIT exon
      17, which encodes a portion of its kinase domain. In contrast, deletions and
      internal tandem duplication (ITD) mutations are found in the juxtamembrane domain
      of c-KIT in approximately 15% of canine MCTs. In addition, ITD c-KIT mutations
      are significantly associated with aberrant KIT protein localization in canine
      MCTs. However, some canine MCTs have aberrant KIT localization but lack ITD c-KIT
      mutations, suggesting that other mutations or other factors may be responsible
      for aberrant KIT localization in these tumors. METHODS: In order to characterize
      the prevalence of mutations in the phospho-transferase portion of c-KIT's kinase
      domain in canine MCTs exons 16-20 of 33 canine MCTs from 33 dogs were amplified
      and sequenced. Additionally, in order to determine if mutations in c-KIT exon 17
      are responsible for aberrant KIT localization in MCTs that lack juxtamembrane
      domain c-KIT mutations, c-KIT exon 17 was amplified and sequenced from 18 canine
      MCTs that showed an aberrant KIT localization pattern but did not have ITD c-KIT
      mutations. RESULTS: No mutations or polymorphisms were identified in exons 16-20
      of any of the MCTs examined. CONCLUSION: In conclusion, mutations in the phospho
      transferase portion of c-KIT's kinase domain do not play an important role in the
      progression of canine cutaneous MCTs, or in the aberrant localization of KIT in
      canine MCTs.

PMID- 16579860
TI  - Hereditary profiles of disorderly transcription?
AB  - BACKGROUND: Microscopic examination of living cells often reveals that cells from
      some cell strains appear to be in a permanent state of disarray without obvious
      reason. In all probability such a disorderly state affects cell functioning. The
      aim of this study was to establish whether a disorderly state could occur that
      adversely affects gene expression profiles and whether such a state might have
      biomedical consequences. To this end, the expression profiles of the 14 genes of
      the proteasome derived from the GEO SAGE database were utilized as a model
      system. RESULTS: By adopting the overall expression profile as the standard for
      normal expression, deviation in transcription was frequently observed. Each
      deviating tissue exhibited its own characteristic profile of over-expressed and
      under-expressed genes. Moreover such a specific deviating profile appeared to be
      epigenetic in origin and could be stably transmitted to a clonal derivative e.g.
      from a precancerous normal tissue to its tumor. A significantly greater degree of
      deviation was observed in the expression profiles from the tumor tissues. The
      changes in the expression of different genes display a network of
      interdependencies. Therefore our hypothesis is that deviating profiles reflect
      disorder in the localization of genes within the nucleus. The underlying cause(s)
      for these disorderly states remain obscure; it could be noise and/or
      deterministic chaos. Presence of mutational damage does not appear to be
      predominantly involved. CONCLUSION: As disturbances in expression profiles
      frequently occur and have biomedical consequences, its determination could prove
      of value in several fields of biomedical research.

PMID- 16579859
TI  - Gender effect on clinical features of achalasia: a prospective study.
AB  - BACKGROUND: Achalasia is a well-characterized esophageal motor disorder but the
      rarity of the disease limits performing large studies on its demographic and
      clinical features. METHODS: Prospectively, 213 achalasia patients (110 men and
      103 women) were enrolled in the study. The diagnosis established by clinical,
      radiographic, and endoscopic as well as manometry criteria. All patients
      underwent a pre-designed clinical evaluation before and within 6 months after the
      treatment. RESULTS: Solid dysphagia was the most common clinical symptom in men
      and women. Chest pain was the only symptom which was significantly different
      between two groups and was more complained by women than men (70.9% vs. 54.5% P
      value = 0.03). Although the occurrence of chest pain significantly reduced after
      treatment in both groups (P < 0.001), it was still higher among women (32% vs.
      20.9% P value = 0.04). In both sexes, chest pain did not relate to the symptom
      duration, LES pressure and type of treatment patients received. Also no
      significant relation was found between chest pain and other symptoms expressed by
      men and women before and after treatment. Chest pain was less frequently reported
      by patients over 56 yrs of age in comparison to those less than 56 yrs (p <
      0.05). CONCLUSION: It seems that chest pain is the distinct symptom of achalasia
      which is affected by sex as well as age and does not relate to the duration of
      illness, LESP and the type of treatment achalasia patients receive.

PMID- 16579861
TI  - Lack of patients? A hypothesis for understanding discrepancies between hospital
      resources and productivity.
AB  - BACKGROUND: Despite a substantial increase in hospital resources, increased
      hospital admissions and out-patient visits, long waiting lists have been a
      significant problem in Norwegian health care. A detailed analysis of the
      development in resource allocation and productivity at St. Olavs University
      Hospital in central Norway was therefore undertaken. METHODS: Resource allocation
      and patient volume was analysed during the period 1995 to 2001. Data were
      analysed both for emergency and elective admissions as well as outpatient visits
      specified into new referrals and follow-up consultations. RESULTS: Full time
      employee equivalents for doctors and nurses increased by 36.6% and 25.9%,
      respectively, and all employees by 28.1%. However, admitted patients, outpatient
      consultations and surgical procedures only increased by 10%, 15% and 8.3%,
      respectively. Thus, the productivity for each hospital employee, defined as
      operations pr. surgeon, outpatient consultations pr. doctor etc. was
      significantly reduced. A striking finding was that although the number of
      outpatient consultations increased, the number of new referrals actually went
      down and the whole increase in activity at the outpatient clinics could be
      explained by a substantial increase in follow-up consultations. This trend was
      more evident in the surgical departments, where some departments actually showed
      a reduction in total outpatient consultations. CONCLUSION: In view of the slow
      increase in hospital activity in spite of a significant increase in resources, it
      can be speculated that patient volume might be a limiting factor for hospital
      activity. The health market (patient population) might not be big enough in
      relation to the investments in increased production capacity (equipment and
      manpower).

PMID- 16579862
TI  - Amphotropic murine leukemia virus is preferentially attached to cholesterol-rich
      microdomains after binding to mouse fibroblasts.
AB  - BACKGROUND: We have recently shown that amphotropic murine leukemia virus (A-MLV)
      can enter the mouse fibroblast cell line NIH3T3 via caveola-dependent
      endocytosis. But due to the size and omega-like shape of caveolae it is possible
      that A-MLV initially binds cells outside of caveolae. Rafts have been suggested
      to be pre-caveolae and we here investigate whether A-MLV initially binds to its
      receptor Pit2, a sodium-dependent phosphate transporter, in rafts or caveolae or
      outside these cholesterol-rich microdomains. RESULTS: Here, we show that a high
      amount of cell-bound A-MLV was attached to large rafts of NIH3T3 at the time of
      investigation. These large rafts were not enriched in caveolin-1, a major
      structural component of caveolae. In addition, they are rather of natural
      occurrence in NIH3T3 cells than a result of patching of smaller rafts by A-MLV.
      Thus cells incubated in parallel with vesicular stomatitis virus glycoprotein
      (VSV-G) pseudotyped MLV particles showed the same pattern of large rafts as cells
      incubated with A-MLV, but VSV-G pseudotyped MLV particles did not show any
      preference to attach to these large microdomains. CONCLUSION: The high
      concentration of A-MLV particles bound to large rafts of NIH3T3 cells suggests a
      role of these microdomains in early A-MLV binding events.

PMID- 16579863
TI  - Reducing uncertainties in global HIV prevalence estimates: the case of Zambia.
AB  - BACKGROUND: The premise for using antenatal care (ANC) clinic data for estimating
      HIV prevalence in the general population is the finding from community studies in
      sub-Saharan Africa that total HIV prevalence in pregnant women attending ANC
      clinics closely approximate levels in the total general population of both women
      and men aged 15-49 years. In this study, the validity of national level HIV
      prevalence estimates for the total general population 15-49 years made from ANC
      clinic and population survey data was assessed. METHODS: In 2001-2002, a national
      population HIV prevalence survey for women 15-49 years and men 15-59 years was
      conducted in Zambia. In the same period, a national HIV sentinel surveillance
      survey among pregnant women attending ANC clinics was carried out. RESULTS: The
      ANC HIV prevalence estimates for age-group 15-49 years (rural: 11.5%; 95% CI,
      11.2-11.8; urban: 25.4%; 95% CI, 24.8-26.0; adjusted national: 16.9%; 95% CI,
      16.6-17.2) were similar to the population survey estimates (rural: 10.8%; 95% CI,
      9.6-12.1; urban: 23.2%; 95% CI 20.7-25.6; national: 15.6%; 95% CI, 14.4-16.9).
      The HIV prevalence urban to rural ratio was 2.2 in ANC and 2.1 in population
      survey estimates. CONCLUSION: The HIV prevalence estimate for the total general
      population 15-49 years derived from testing both women and men in the population
      survey was similar to the estimate derived from testing women attending ANC
      clinics. It shows that national HIV prevalence estimates for adults aged 15-49
      years can also be obtained from ANC HIV sentinel surveillance surveys with good
      coverage when ANC attendance and fertility are high.

PMID- 16579864
TI  - Using intervention time series analyses to assess the effects of imperfectly
      identifiable natural events: a general method and example.
AB  - BACKGROUND: Intervention time series analysis (ITSA) is an important method for
      analysing the effect of sudden events on time series data. ITSA methods are quasi
      experimental in nature and the validity of modelling with these methods depends
      upon assumptions about the timing of the intervention and the response of the
      process to it. METHOD: This paper describes how to apply ITSA to analyse the
      impact of unplanned events on time series when the timing of the event is not
      accurately known, and so the problems of ITSA methods are magnified by
      uncertainty in the point of onset of the unplanned intervention. RESULTS: The
      methods are illustrated using the example of the Australian Heroin Shortage of
      2001, which provided an opportunity to study the health and social consequences
      of an abrupt change in heroin availability in an environment of widespread harm
      reduction measures. CONCLUSION: Application of these methods enables valuable
      insights about the consequences of unplanned and poorly identified interventions
      while minimising the risk of spurious results.

PMID- 16579865
TI  - Periodicity of SNP distribution around transcription start sites.
AB  - BACKGROUND: Several millions single nucleotide polymorphisms (SNPs) have already
      been collected and deposited in public databases and these are important
      resources not only for use as markers to identify disease-associated genes, but
      also to understand the mechanisms that underlie the genome diversification.
      RESULTS: A spectrum analysis of SNP density distribution in the genomic regions
      around transcription start sites (TSSs) revealed a remarkable periodicity of 146
      nucleotides. This periodicity was observed in the regions that were associated
      with CpG islands (CGIs), but not in the regions without CpG islands (nonCGIs). An
      analysis of the sequence divergence of the same genomic regions between humans
      and chimpanzees also revealed a similar periodical pattern in CGI. The
      occurrences of any mono- or di-nucleotide sequences in these regions did not
      reveal such a periodicity, thus indicating that an interpretation of this
      periodicity solely based on the sequence-dependent susceptibility to mutation is
      highly unlikely. CONCLUSION: The periodical patterns of nucleotide variability
      suggest the location of nucleosomes that are phased at TSS, and can be viewed as
      the genetic footprint of the chromatin state that has been maintained throughout
      mammalian evolutionary history. The results suggest the possible involvement of
      the nucleosome structure in the promoter function, and also a fundamental
      functional/structural difference between the two promoter classes, i.e., those
      with and without CGIs.

PMID- 16579867
TI  - Does it make sense to "desens"? Aspirin desensitization in the treatment of
      chronic rhinosinusitis.

PMID- 16579866
TI  - Delayed functional maturation of natural regulatory T cells in the medulla of
      postnatal thymus: role of TSLP.
AB  - BACKGROUND: Generation of functional (CD4+)(CD8-)CD25+ regulatory T cells (Treg)
      in the murine thymus depends on FoxP3. Removal of the thymus from neonatal mice
      has been shown to result in a multiple organ autoimmune disease phenotype that
      can be prevented by introducing the FoxP3+ Treg population to the animal. It has
      therefore, been proposed that functional FoxP3+ Treg cells are not made in the
      neonatal thymus; however, it remains unclear when and where functional
      (FoxP3+)(CD4+)(CD8-)CD25+ thymocytes are generated in postnatal thymus. RESULTS:
      We report that neither FoxP3 mRNA nor protein is expressed in (CD4+)(CD8-)CD25+,
      or (CD4+)(CD8-)CD25- thymocytes until 3-4 days post birth, despite the presence
      of mature (CD4+)(CD8-)CD25+/- thymocytes in the thymus by 1-2 days after birth.
      (FoxP3-)(CD4+)(CD8-)CD25+ thymocytes from day 2 newborn mice show no Treg
      activity. Interestingly, we are able to detect low numbers of FoxP3+ thymocytes
      dispersed throughout the medullary region of the thymus as early as 3-4 days post
      birth. Expression of FoxP3 is induced in embryonic day 17 fetal thymus organ
      culture (FTOC) after 4-6 days of in vitro culture. Treatment of FTOCs with thymic
      stromal derived lymphopoietin (TSLP) enhanced expression of FoxP3, and blocking
      the TSLP receptor reduces FoxP3 expression in FTOC. Furthermore, TSLP stimulates
      FoxP3 expression in purified (CD4+)CD8- thymocytes, but not in (CD4+)CD8+, (CD4
      )CD8+ and (CD4-)CD8- thymocytes. CONCLUSION: Expression of FoxP3 or Treg
      maturation is ontogenically distinct and kinetically delayed from the generation
      of (CD4+)(CD8-)CD25+ or (CD4+)(CD8-)CD25- thymocytes in the postnatal thymus.
      TSLP produced from medullary thymic epithelia cells (mTEC) contributes to the
      expression of FoxP3 and the maturation of natural regulatory T cells. Overall,
      these results suggest that the development of Treg cells requires paracrine
      signaling during late stages of thymocyte maturation that is distinct from
      signaling during positive or negative selection.

PMID- 16579868
TI  - Mucin gene expression in rhinitis syndromes.
AB  - Rhinitis and rhinosinusitis are often associated with airway diseases such as
      asthma, cystic fibrosis, and nasal polyposis. In these diseases, the alteration
      of both the quantity and quality of mucus results in an impaired mucociliary
      clearance, and this produces, in extreme cases, the airway obstruction. Mucins
      are the major component in mucus and are responsible for its viscoelastic
      properties. Mucin expression patterns have been shown to be altered in rhinitis
      associated diseases. It has been proposed that this is one of the causes of
      hyperviscid mucus plugs in these pathologies. For this reason, the study of mucin
      expression and regulation in upper- and lower-airway diseases, such as asthma,
      cystic fibrosis, and nasal polyposis, may be crucial for the development of new
      therapies against mucus hypersecretion. In this review, we report major findings
      regarding mucin expression and regulation in rhinitis syndromes.

PMID- 16579869
TI  - Mechanisms of aspirin sensitivity.
AB  - In some asthma patients, nonsteroidal anti-inflammatory drugs (NSAIDs) induce
      bronchospasm, rhinorrhea, and nasal obstruction. NSAID-induced reactions appear
      to be caused by the inhibition of cyclooxygenase-1 (Cox-1); this in turn
      activates the lipoxygenase pathway, which eventually increases the release of
      cysteinyl leukotrienes (Cys-LTs) that induces bronchospasm and nasal obstruction.
      With regard to the metabolism of arachidonic acid (AA) in NSAID-intolerant
      asthmatic patients, the following changes have been observed: 1) A low production
      of prostaglandin E2, seemingly due to deficient Cox-2 regulation; 2) an increased
      expression of leukotriene-C4 synthase; and 3) a reduced production of metabolites
      (lipoxins) released through the transcellular metabolism of AA. NSAID-intolerant
      asthmatics have higher basal levels of Cys-LT than NSAID-tolerant asthmatics.
      Moreover, Cys-LT levels in NSAID-intolerant asthmatics increase remarkably
      following NSAID provocation testing. There has been no explanation to date that
      connects all these findings, although an anomaly in the regulation of Cox-2 is
      probably accountable.

PMID- 16579870
TI  - Differential diagnosis of eosinophilic chronic rhinosinusitis.
AB  - Eosinophilic chronic rhinosinusitis (ECRS) encompasses a wide variety of
      etiologies. To date, a unifying pathophysiologic mechanism remains elusive.
      Eosinophilia is frequently, but not exclusively, caused by immunoglobulin (Ig)E
      mediated hypersensitivity and is dominated by the associated cytokine milieu of
      Th2 inflammation. The provisional subcategories of ECRS include superantigen
      induced eosinophilic chronic rhinosinusitis, allergic fungal sinusitis,
      nonallergic fungal eosinophilic chronic rhinosinusitis, and aspirin-exacerbated
      eosinophilic chronic rhinosinusitis. Within each subcategory, recent findings
      supporting distinct mechanisms that promote eosinophilic infiltration are
      presented, and, therefore, targeted therapeutic interventions with specific
      antibacterial, antifungal, or immune modulation may be indicated.

PMID- 16579872
TI  - The impact of allergic and nonallergic rhinitis on pediatric sinusitis.
AB  - There is a great deal of published evidence that there is a relationship between
      both allergic and nonallergic rhinitis and sinusitis in both pediatric and adult
      patients. The relationship between rhinitis and sinusitis may involve
      inflammation in one compartment leading to secondary inflammation in the other
      compartment, such as in the case of rhinitis leading to obstruction of the
      osteomeatal complex. The relationship may also involve individual manifestations
      of a shared process, such as allergic disease. A better understanding of the
      relationship between rhinitis and sinusitis may significantly influence the
      treatment of these common and important conditions.

PMID- 16579871
TI  - Nonallergic rhinitis with eosinophilia syndrome.
AB  - Nonallergic rhinitis with eosinophilia syndrome (NARES) is a clinical syndrome
      comprising symptoms consistent with allergic rhinitis in which an absence of
      atopy has been demonstrated by allergen skin testing, and nasal cytology analysis
      demonstrates more than 20% eosinophils. Anosmia is a prominent feature not shared
      with allergic rhinitis. The pathophysiology of NARES is poorly understood, but a
      key component involves a self-perpetuating, chronic eosinophilic nasal
      inflammation with development of nasal micropolyposis and polyposis. Mast cells
      likely play an important role as well. NARES is a risk factor for the development
      of nasal polyposis and aspirin sensitivity, as well as obstructive sleep apnea.
      Treatment consists mainly of intranasal corticosteroids with or without the
      addition of second-generation antihistamines and/or leukotriene-receptor
      antagonists.

PMID- 16579873
TI  - The role of endoscopy in the allergist's office.
AB  - The introduction of nasal endoscopy has revolutionized the diagnosis and
      management of patients with sinonasal disorders. The brilliant illumination and
      magnification afforded by the nasal endoscopes has markedly enhanced the current
      knowledge of sinonasal anatomy and understanding of patterns of mucociliary
      clearance. Nasal endoscopy facilitates accurate diagnosis of sinonasal pathology
      and assessment of response to medical and surgical therapy by serial examination.
      Rigid telescopes also facilitate office-based procedures, including cultures of
      purulent secretions and biopsy of sinonasal masses. Indeed, nasal endoscopy forms
      the foundation of the surgical paradigm of functional endoscopic sinus surgery.
      In this review, the rationale, technique and current state of endoscopic
      applications of nasal endoscopy are described, with special focus on the role of
      endoscopy in the allergist's office.

PMID- 16579874
TI  - Treating allergic rhinitis in pregnancy.
AB  - Numerous pregnant women suffer from allergic rhinitis, and particular attention
      is required when prescribing drugs to these patients. In addition, physiologic
      changes associated with pregnancy could affect the upper airways. Evidence-based
      guidelines on the management of allergic rhinitis have been published. Medication
      can be prescribed during pregnancy when the apparent benefit of the drug is
      greater than the apparent risk. Usually, there is at least one "safe" drug from
      each major class used to control symptoms. All glucocorticosteroids are
      teratogenic in animals but, when the indication is clear (for diseases possibly
      associated, such as severe asthma exacerbation), the benefit of the drug is far
      greater than the risk. Inhaled glucocorticosteroids (eg, beclomethasone or
      budesonide) have not been incriminated as teratogens in humans and are used by
      pregnant women who have asthma. A few H1-antihistamines can safely be used as
      well. Most oral decongestants (except pseudoephedrine) are teratogenic in
      animals. There are no such data available for intranasal decongestants. Finally,
      pregnancy is not considered to be a contraindication for the continuation of
      immunotherapy.

PMID- 16579876
TI  - New targets for modifying mast cell activation in asthma.
AB  - Mast cells play a central role in innate immunity and in orchestrating the
      asthmatic response. Current medication relies on beta-agonists to relieve
      bronchoconstriction and steroids to reduce inflammation. However, recently drugs
      such as leukotriene-receptor antagonists and anti-immunoglobulin E have come on
      to the market. In this paper, a number of potential targets for modifying mast
      cell activation in asthma are reviewed. Some are already under study, including
      clinical trials (eg, tryptase inhibitors); others are more speculative (eg,
      inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity). In each
      case, where data are available, the action of the agents on human lung mast cells
      is described.

PMID- 16579875
TI  - Sex-specific genetic architecture of asthma-associated quantitative trait loci in
      a founder population.
AB  - Identifying genes that influence susceptibility to asthma-related and atopy
      related phenotypes has been challenging, owing to clinical heterogeneity and a
      complex underlying genetic architecture that includes both gene-gene and gene
      environment interactions. In this article, we report the results of genome-wide
      linkage and association studies of eight asthma-associated quantitative traits in
      the Hutterites, a founder population of European descent. Our study revealed
      significant sex-specific genetic architecture for at least five of these traits,
      and identified 13 genome-wide significant quantitative trait loci (QTL) by
      linkage or association that are present in only one of the sexes (nine in males,
      four in females).

PMID- 16579881
TI  - [Reliability of medication errors].

PMID- 16579877
TI  - Sideline management of asthma.
AB  - The timely, efficient, and effective sideline management of asthma must be
      grounded on an understanding of the disease processes, awareness of evidence
      based therapeutic intervention, and thorough knowledge of the individual
      athlete's medical history and current physical condition. There is accumulating
      evidence that exercise-induced airway narrowing, if unrecognized or inadequately
      treated, can progress to a severe life-threatening status and should always be
      viewed as a potential medical emergency. A widening range of therapeutic measures
      is currently available to prevent and to treat exercise asthma, and treatment
      must be tailored to the individual circumstances to optimize response.

PMID- 16579883
TI  - [Combination therapy with acetylsalicylic acid and non-aspirin nonsteroidal anti
      inflammatory drugs].
AB  - Patients may require both low-dose aspirin (ASA) and a nonsteroidal anti
      inflammatory drug (NSAID). This raises the questions of whether NSAIDs may
      inhibit the cardioprotective effects of low-dose ASA; whether the
      cardioprotective effect of low-dose ASA can be obtained by NSAIDs: and whether
      the combination of low-dose ASA and NSAIDs increases the risk of adverse effects.
      This review attempts to answer these questions.

PMID- 16579882
TI  - [Disagreement between physicians' medication records and information given by
      patients].
AB  - INTRODUCTION: A survey was conducted to evaluate the level of disagreement
      between the drug records of family doctors and information provided by patients
      at the time of hospitalisation. MATERIALS AND METHODS: One hundred patients
      acutely admitted to a hospital department of medicine were consecutively included
      if the patient ingested more than two non-OTC drugs. A second drug interview was
      performed shortly after admission, and the patient's current medication was
      recorded. If no written medical record from the referring family doctor was
      available at the time of admission, the doctor was contacted by phone for
      supplementary information. Discrepancies between the information given by the
      patient and the medical records of family doctors were recorded. The results were
      analysed blindly by two of the authors (one senior and one junior doctor) to
      determine if the discrepancies were clinically relevant for the patient. RESULTS:
      We found at least one clinically relevant and potentially dangerous discrepancy
      in the medical records of 40% (95% CI 30%-50%) of the patients. In all,
      discrepancies were found in the drug lists of 63% of the patients. The patients
      with discrepancies were similar in age, sex, way of hospitalization and number of
      drugs ingested, compared to those without discrepancies. Afterwards the family
      doctors were invited to a meeting in which these problems were evaluated.
      CONCLUSION: We conclude that there is an urgent need for improvement in the
      communication between the primary and secondary health care sectors concerning
      medication being prescribed for patients with chronic diseases. The large number
      of discrepancies in the drug records of patients in this study is discouraging.

PMID- 16579884
TI  - [Transport proteins as drug targets in Plasmodium falciparum. New perspectives in
      the treatment of malaria].
AB  - The malaria parasite, Plasmodium falciparum, infects and replicates in human
      erythrocytes. Through the use of substrate-specific transport proteins, P.
      falciparum takes up nutrients from the erythrocyte's cytoplasm. The sequencing
      and publishing of the P. falciparum genome have made it possible to identify,
      clone and characterise a number of these transport proteins from the parasite.
      Since the P. falciparum transport proteins differ from their human homologues,
      they may provide potential drug targets in the treatment of malaria. An example
      of a P. falciparum transport protein which seems promising as a drug target is
      the parasite's hexose transporter. Furthermore, the antimalarial drug artemisinin
      has been shown to interact specifically with the parasite's Ca2+ pump. A number
      of other transport proteins are also discussed as possible drug targets.

PMID- 16579885
TI  - [Light therapy for managing sleep and behavioral disturbances and depressive
      symptoms in dementia].

PMID- 16579886
TI  - [Trauma of the popliteal artery. Twenty three patients treated during a 27-year
      period].
AB  - INTRODUCTION: Trauma of the popliteal artery is a rare event. During a period of
      14 years, only 59 cases were registered in Denmark in the national register
      Karbase. There are several pitfalls in the management of popliteal artery lesions
      which may lead to an increased risk of amputation. This article analyses our own
      results and discusses selected topics concerning the management of popliteal
      artery injuries. MATERIALS AND METHODS: The records of 23 patients treated for
      injury of the popliteal artery over a 27-year period were reviewed. A follow-up
      investigation was performed. The patients' Doppler pressure was measured.
      RESULTS: There were three (13%) amputations. At the time of follow-up, 5 of the
      patients were dead; 1 person was living abroad. Of the remaining 17 patients, 15
      had no vascular symptoms; 2 patients had been amputated initially, and 1 patient
      had been treated conservatively. DISCUSSION: Management of a popliteal artery
      injury can be difficult and requires an experienced approach. Our results reveal
      excellent long-term patency of the vascular reconstruction with the saphenus
      vein. Furthermore, amputation is almost always due to major soft tissue injury or
      delayed surgical intervention. The amputation rate of 13% in this material is in
      line with that in the literature. We recommend that every patient suffering from
      major trauma of an extremity have a Doppler pressure measurement performed and
      registered during the initial evaluation in the casualty department.

PMID- 16579887
TI  - [Patients' satisfaction with their hospital stay at the Department of Psychiatry,
      Amager Hospital, in 2000 and 2003].
AB  - INTRODUCTION: Our goal was to compare patients' satisfaction with their hospital
      stay at the Department of Psychiatry, Copenhagen University Hospital, Amager,
      before and after the department was moved to newly built facilities. MATERIALS
      AND METHODS: In 2000 and again in 2003, patients who were about to be discharged
      from the department were asked to anonymously fill in a 24-item questionnaire
      related to their satisfaction with their recent hospital stay. RESULTS: The
      percentage of participants was 39% of discharged patients in 2000 and 33% in
      2003. A high percentage rated their general satisfaction with the hospital stay
      as either "good" or "very good" (94% in 2000 and 88% in 2003). From 2000 to 2003,
      we noted a significant (23%) increase in the percentage who rated their
      satisfaction with the buildings as either "good" or "very good". In other areas,
      there was reduced patient satisfaction. We noted a reduction with respect to the
      respondents' satisfaction with the hospital staff on specific matters; for
      instance, a significant (23%) reduction in the respondents' perception of the
      hospital staff having spent sufficient time with them. CONCLUSION: After the
      department was moved to newly built facilities, patients' satisfaction with the
      buildings appears to have increased. In other areas, such as satisfaction with
      the hospital staff on specific matters, patient satisfaction appears to have
      decreased. The results should be interpreted with caution due to the low
      participation rate.

PMID- 16579888
TI  - [Allergy in general practice in Arhus County. Quality assessment of diagnosis,
      treatment and instructions to patients: I. Asthma].
AB  - INTRODUCTION: The aim of this study was to evaluate adult patients examined in
      general practice on suspicion of having asthma. MATERIALS AND METHODS: A total of
      46 patients suspected of having asthma underwent a second specialist
      investigation, which demonstrated that 28 of them had asthma. Through interviews
      of patients and a questionnaire completed by the primary physician, information
      on diagnostic strategy, general practice diagnosis, suggested treatments and
      patients' knowledge about asthma was determined. RESULTS: In 65% of the patients
      investigated for possible asthma in general practice, the specialist examination
      did not provide any major suggestions for changes, while one in every three
      patients would have benefited from a secondary specialist examination. The
      largest group was 7 of 18 patients who did not have asthma but who suffered from
      chronic or recurrent symptoms. Also, one in four of the patients with a final
      diagnosis of asthma would have benefited from a specialist examination because of
      uncertain diagnosis, disease severity and/or the possibility of allergen-specific
      treatment. The medical treatments suggested by the general practitioners followed
      modern treatment principles. Just over half of the patients with a final
      specialist diagnosis of asthma were familiar with the basic disease mechanisms,
      but only 7% of them would change their therapy in relation to disease severity
      without first contacting their physicians. CONCLUSION: Patients with chronic or
      recurrent symptoms should be referred to specialists more often, and patients who
      could potentially benefit from allergen-specific treatment, such as allergen
      prevention, should be evaluated by an allergy specialist. There is a need for
      increased patient education.

PMID- 16579889
TI  - [Allergy in general practice in Arhus County. Quality assessment of diagnosis,
      treatment and instructions to patients: II. Rhinitis].
AB  - INTRODUCTION: The aim of this study was to evaluate adult patients in general
      practice suspected of having rhinitis. MATERIALS AND METHODS: A total of 72
      patients suspected of having rhinitis underwent a secondary specialist
      investigation, resulting in 55 final specialist diagnoses of rhinitis. Through
      interviews of patients and a questionnaire mailed to the primary physician,
      information on diagnostic strategy, final diagnosis, suggested treatments and
      patients' knowledge about rhinitis were determined. RESULTS: One third of the 72
      patients examined for possible rhinitis would have benefited from a supplementary
      specialist examination, where one group was made up of patients with negative
      allergy tests and chronic symptoms of either non-rhinitis disease or vasomotoric
      rhinitis and the other group was made up of patients with severe seasonal
      allergic rhinitis, who would benefit from immunotherapy. The suggested medical
      treatments followed modern treatment principles. Of the patients with a final
      diagnosis of rhinitis, only one third were informed about treatment principles
      with inhalation steroids, while half of the patients knew about the basic
      principles of antihistamine treatment. Of 53 patients with rhinitis, 6 were
      prepared to change medical treatment without first contacting their physician.
      CONCLUSION: Patients with chronic or recurrent symptoms should be referred to
      specialists more often, and patients who might benefit from allergen-specific
      treatment, such as immunotherapy or allergen prevention, should be evaluated by
      an allergy specialist. Patients with rhinitis should be given more information on
      disease mechanisms and treatment principles.

PMID- 16579890
TI  - [Allergy in general practice in Arhus County. Quality assessment of diagnosis,
      treatment and instructions to patients. III. Allergy testing].
AB  - INTRODUCTION: The aim of this study was to compare the allergy test with the skin
      prick test and the specific IgE by Phadiatop test to a purely clinical allergy
      diagnosis by an allergy specialist in adult patients previously tested in general
      practice. MATERIALS AND METHODS: A total of 103 patients suspected of having
      asthma and/or rhinitis were re-evaluated with a clinical diagnosis and the two
      allergy tests. Both the patient and the individual general practitioner were
      asked about existing allergy diagnosis. RESULTS: The two test systems showed
      large differences in a semiquantitative linear system with an explained variation
      (r2) of only 8%. In comparison to a purely clinical diagnosis, they were
      diagnostically equal with both tests, with an additional 15% positive reactions
      of which 25% were judged clinically active. Both tests resulted in about 33%
      false-positive tests classified as clinically inactive. In the case of a positive
      Phadiatop test and clinically active allergy, both the patient and the general
      practitioner reported identical specialist diagnoses in about 75% of cases, while
      in 20-50% of the cases an identical diagnosis was reported when the clinical
      diagnosis was qualitatively different from the result of Phadiatop. CONCLUSION:
      The results of the two test systems often differ, and they both detect extra
      positive tests, in which case they should be used in a serial manner. Both tests
      often result in a false-positive diagnosis, and identification of clinically
      relevant positive tests often requires an experienced medical evaluation.

PMID- 16579891
TI  - [Reduced post-partum bleeding after treatment with sublingual misoprostol: a
      randomized double-blind clinical study in a developing country--secondary
      publication)].
AB  - Post-partum haemorrhage is the most common cause of maternal death in third-world
      countries. The objective of this study was to evaluate whether routine
      administration of sublingual misoprostol, 600 g, reduces post-partum haemorrhage.
      Significantly fewer women in the misoprostol group experienced a loss of > or =
      1,000 ml (11% vs. 17%; 0.66 (0.45-0.98)) or > or = 1,500 ml (2% vs. 8%; 0.28
      (0.12-0.64)) of blood. We conclude that sublingual misoprostol reduces the
      frequency of severe post-partum haemorrhage.

PMID- 16579892
TI  - [Intestinal side effects of COX-2 inhibitors].
AB  - COX-2 inhibitors and NSAIDs have similar analgesic, anti-inflammatory and severe
      upper intestinal side effects. Adding to the sparse and casuistic reports, a
      further five cases of severe lower intestinal illness associated with COX-2
      inhibitor ingestion are presented. Diarrhoea due to microscopic colitis was
      associated with short-time ingestion of refecoxib and celecoxib by two patients.
      Refecoxib intake for two months was associated with spontaneous perforation of a
      well-functioning J-pouch in a patient with ulcerative colitis. Intake of
      celecoxib and etodolac was associated with colonic ulceration and stricture. Side
      effects related to COX-2 inhibitors are similar to those related to NSAIDs.

PMID- 16579893
TI  - [Work-related asthma caused by IgE-verified allergy to methylene di-isocynate].
AB  - A 44-year-old blacksmith periodically exposed to methylene di-isocynate (MDI)
      from foaming processes over the course of eight years developed an acute episode
      of asthma shortly after high exposure to MDI. The respiratory symptoms declined
      gradually over some months. A year later the specific IgE to MDI was still high
      (23.92 KU/l), but lung function (FEV1, PEF and FVC) was normal and no bronchial
      hyperreactivity was observed. He is still working at the same factory under
      respiratory health surveillance.

PMID- 16579898
TI  - [Kernicterus and sulfamethizole treatment].

PMID- 16579899
TI  - [Prevention of kernicterus in the neonatal period].

PMID- 16579901
TI  - [Misleading interpretation of the relation between obesity and energy balance].

PMID- 16579902
TI  - [Occupational therapy in connection with hand surgery].

PMID- 16579905
TI  - [Discussion about quality of life and evidence-based medicine].

PMID- 16579914
TI  - A new obstetric forceps for the training of junior doctors: a comparison of the
      spatial dispersion of forceps blade trajectories between junior and senior
      obstetricians.
AB  - OBJECTIVE: The purpose of this study was to create a new instrument for the
      training of doctors in the use of forceps and to compare the trajectories of
      forceps blades between junior and senior obstetricians. STUDY DESIGN: We equipped
      a simulator and forceps with spatial location sensors. The head of the fetus was
      in an occipitoanterior location, at a "+5" station. Forceps blade trajectories
      were analyzed subjectively with the 3-dimensional spatial graph and objectively
      based on 3 points of special interest. Each obstetrician performed 4 forceps
      blades placements. We compared the trajectories of junior and senior
      obstetricians. RESULTS: For senior operators, spatial dispersion was "excellent,"
      "very good," or "good" in 92% of cases, whereas this was the case for only 38% of
      junior doctors (92% vs 38%; P < .001). CONCLUSION: A new instrument has been
      designed to demonstrate the trajectory of forceps blades during application in a
      simulator. The instrument captures the difference in experience between senior
      and junior clinicians.

PMID- 16579915
TI  - Apoptosis and its role in the trophoblast.
AB  - During early placentation the trophoblast of the human placenta differentiates to
      the villous and extravillous types of trophoblast. Villous trophoblast provides
      the epithelial cover of the placental villous trees in direct contact to maternal
      blood. Extravillous trophoblast invades maternal uterine tissues thus directly
      contacting maternal stromal and immune cells. A subset of extravillous
      trophoblast, endovascular trophoblast initially occludes the lumen of spiral
      arteries and comes into direct contact with maternal blood. In recent years
      apoptosis has been described in both types of trophoblast and the importance of
      this cascade for the normal function of the trophoblast has become obvious. One
      feature of serious conditions such as preeclampsia or intrauterine growth
      restriction is changes in apoptosis regulation in villous and/or extravillous
      trophoblast resulting in altered trophoblast invasion and/or shedding into the
      maternal circulation. This review summarizes recent findings on trophoblast
      apoptosis in normal and pathologic pregnancies.

PMID- 16579916
TI  - Lowering the dose of antenatal steroids: the effects of a single course of
      betamethasone on somatic growth and brain cell proliferation in the rat.
AB  - We investigated the effects of a single course of antenatal betamethasone on
      neonatal somatic and brain development. On day 20 of gestation, pregnant rats
      were injected with either with 170 microg kg(-1) body weight of betamethasone
      ("clinically-equivalent dose," equivalent to 12 mg twice, 24 hours apart) or half
      this dose or vehicle. Pups (8-11 animals per experimental group per timepoint per
      gender) were analyzed at 1 (P1), 2, and 21 days after birth. We report that
      betamethasone induced a significant dose-dependent decrease of somatic
      measurements in both genders. At P1 cell proliferation was affected by the
      "clinically equivalent dose" only in the subventricular zone in both genders and
      in the hippocampus in males. In summary, we show for the first time that a lower
      dose (equivalent to 6 mg) induces fewer and less severe effects on somatic
      growth, whereas it does not affect cell proliferation within the brain.

PMID- 16579917
TI  - Neuropsychological performance in normal pregnancy and preeclampsia.
AB  - OBJECTIVE: The objective of the study was to evaluate neurocognitive function in
      preeclampsia and normal pregnancy. STUDY DESIGN: Three groups (each n = 15) were
      studied before and after delivery using standard neurocognitive test techniques.
      Group A consisted of normal laboring patients; group B, preeclamptics receiving
      magnesium; and group C, women in preterm labor receiving MgSO4 tocolysis (Mg
      control). The tests, examining attention, working memory, explicit memory,
      auditory comprehension, and measures for emotional distress, pain, and fatigue
      were analyzed via 4-way multivariate analysis of variance and multiple t tests.
      RESULTS: Preeclamptics receiving MgSO4 had better attention and working memory (P
      = .05), compared with normal laboring women and the preterm patients. Explicit
      memory was impaired in all groups, and this could not be accounted for by pain or
      emotional distress. CONCLUSION: We could detect no cognitive defects in
      preeclamptics, compared with normotensive gravidas, at least while the cerebral
      vasodilator MgSO4 is being infused.

PMID- 16579918
TI  - Recurrent stress incontinence is associated with decreased neuromuscular function
      in the striated urethral sphincter.
AB  - OBJECTIVE: The study aim was to compare urethral neuromuscular function in stress
      incontinent women with and without previous incontinence surgery. STUDY DESIGN:
      Urethral electromyographic (EMG) data for women with recurrent urodynamic stress
      incontinence following 1 previous continence procedure were compared to age- and
      parity-matched women with urodynamic stress incontinence (USI) without previous
      incontinence surgery. The cases with recurrent USI included 13 women with 1
      previous sling and 13 women with 1 previous Burch. EMG signals were obtained at
      rest, with cough, and during pelvic floor contraction using an automated software
      program. EMG data from recurrent cases were compared with controls. RESULTS:
      Women with recurrent stress incontinence after 1 previous continence procedure
      had lower quantitative EMG values than women without previous surgery.
      Specifically, we observed that women with previous sling had significantly lower
      quantitative EMG values with cough (P = .007), while baseline and squeeze values
      were not significantly different. Women with previous Burch had cough EMG values
      intermediate between the control and previous sling group, which trended toward
      statistical significance (P = .057). CONCLUSION: Women with recurrent urodynamic
      stress incontinence after previous slings have poorer urethral neuromuscular
      function than stress incontinent women without previous incontinence surgery.

PMID- 16579919
TI  - Damage to ovarian reserve associated with laparoscopic excision of endometriomas:
      a quantitative rather than qualitative injury.

PMID- 16579921
TI  - Skeletal muscle heavy-chain polypeptide 3 and myosin binding protein H in the
      pubococcygeus muscle in patients with and without pelvic organ prolapse.
AB  - OBJECTIVE: The purpose of this study was to compare gene expression of skeletal
      muscle heavy-chain polypeptide 3 (MYH3) and myosin binding protein H (MyBP-H) in
      the pubococcygeus muscle of patients with pelvic organ prolapse and controls.
      STUDY DESIGN: Genes previously identified by microarray genechip analysis of
      pubococcygeus muscle biopsies were examined using real-time quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) analysis. Specimens were
      obtained from 17 patients with stage III or IV pelvic organ prolapse and 23
      controls with minimal to no prolapse. Glyceraldehyde 3-phosphate dehydrogenase
      (GAPDH) was used as the housekeeping gene. Samples and controls were run in
      triplicate in separate wells, and the levels of gene expression were analyzed
      quantitatively using the comparative critical threshold (Ct) method. Differences
      in gene expression were analyzed using Wilcoxon rank-sum testing. RESULTS:
      Significant differences in gene expression were observed between patients with
      prolapse and controls for both genes. Skeletal muscle myosin heavy-chain
      polypeptide 3 was 6.5 times underexpressed in patients with pelvic organ prolapse
      compared to controls (P = .028). Similarly, myosin binding protein H was 3.2
      times underexpressed in patients with prolapse (P = .042). Overall, patients had
      a mean age of 62.4 +/- 6.5 years compared with controls with a mean age of 45.3
      +/- 7.4 years (P < .001), so analysis was also performed on an age-matched subset
      of 8 patients and controls (mean ages of 58.1 +/- 5.4 years and 53.3 +/- 5.0
      years, respectively, P = .02) with similar results. Prolapse patients in this
      subset were similar in parity and race to controls but had lower body mass index
      (23.2 vs 29.9, P = .04). MYH3 was 10.9 times underexpressed in patients with
      pelvic organ prolapse compared to controls (P = .027). MyBP-H was 10.4 times
      underexpressed in patients with prolapse (P = .036). CONCLUSION: These findings
      suggest that the differences between patients with advanced pelvic organ prolapse
      and controls may be related to differential gene expression of structural
      proteins related to myosin. Specifically, advanced pelvic organ prolapse may be
      related to down-regulation of skeletal muscle heavy-chain polypeptide 3 and
      myosin binding protein H.

PMID- 16579923
TI  - Perinatal complications among different Asian-American subgroups.
AB  - OBJECTIVE: This study was undertaken to investigate the differences in perinatal
      outcomes among Asian American/Pacific Islander (AAPI) women. STUDY DESIGN: A
      retrospective cohort study of all Japanese, Chinese, and Filipina women who
      delivered at University of California, San Francisco from 1985 to 2001 examined
      the incidence of gestational diabetes, preeclampsia, and preterm delivery.
      RESULTS: Among the 6511 women delivered during the study period, the incidence of
      preeclampsia was highest among Filipina women (6.8%) compared with the Chinese
      and Japanese women (4.0% and 3.7%, respectively, P < .001). Gestational diabetes
      was most common in the Chinese and Filipina women (6.5% and 6.1%, respectively)
      compared with the Japanese women (3.4%, P = .013). Preterm delivery was also
      highest among Filipina women both before 37 weeks (12.2%, P < .001) and 34 weeks
      (4.8%, P = .004). These differences remained statistically significant after
      controlling for potential confounding variables. CONCLUSION: We found significant
      differences in rates of preeclampsia, gestational diabetes, and preterm delivery
      in the Chinese, Japanese, and Filipino subgroups. In studies of race and
      ethnicity, it is important to examine Asian subgroups separately.

PMID- 16579924
TI  - A trial that compares Monsel's paste with ball electrode for hemostasis after
      loop electrosurgical excision procedure.
AB  - OBJECTIVE: The purpose of this study was to compare Monsel's paste with
      fulguration with ball electrode for hemostasis after loop electrosurgical
      excision procedure. STUDY DESIGN: One hundred healthy women were assigned
      randomly by computer-generated random numbers to ball electrode or thickened
      Monsel's paste for hemostasis after loop electrosurgical excision procedure.
      Patients rated pain during hemostasis using a visual analog scale. At 2 weeks,
      postprocedural vaginal discharge was rated on a Likert scale. Pathology was
      reviewed for dysplasia grade and margin status. Recurrent dysplasia on repeat
      Papanicolaou tests was noted. RESULTS: Six patients (2 Monsel's and 4
      fulguration) required an alternate method of hemostasis. Patient demographics,
      postprocedural discharge, and recurrent dysplasia were comparable between the 2
      groups. Visual analog scale scores and hemostasis time were significantly higher
      in the fulguration group. Estimated blood loss, although higher in the
      fulguration group, was not significant between groups. CONCLUSION: Monsel's paste
      and fulguration with ball electrode appear be equally effective as hemostatic
      agents after loop electrosurgical excision procedure.

PMID- 16579926
TI  - Women's health 18 years after rupture of the anal sphincter during childbirth:
      II. Urinary incontinence, sexual function, and physical and mental health.
AB  - OBJECTIVE: We studied maternal health 18 years postpartum in women having
      sustained an anal sphincter tear and controls. STUDY DESIGN: We assessed symptoms
      with the short form of the urogenital distress inventory, the female sexual
      function index, and physical and mental health with the Short Form-12 summary
      scales. RESULTS: Women with a sphincter tear had no increased risk of urinary
      symptoms (54 of 251, 22%, versus 51 of 273, 19%, risk ratio 1.2, 95% confidence
      interval 0.8 to 1.6) or sexual symptoms (84 of 223, 38%, versus 90 of 230, 39%,
      risk ratio 1.0, 95% confidence interval 0.8 to 1.2). Their physical health was
      also similar to controls (mean score +/- SD, 47 +/- 7 versus 47 +/- 6), whereas
      their mental health was slightly lower (score 45 +/- 6 versus 46 +/- 6,
      difference 1, 95% confidence interval 0 to 2, P = .05). CONCLUSION: Women who
      sustained an anal sphincter tear have no more urinary or sexual symptoms 18 years
      after delivery.

PMID- 16579925
TI  - Perfusion studies of glyburide transfer across the human placenta: implications
      for fetal safety.
AB  - OBJECTIVE: Gestational diabetes affects up to 5% of women. Oral hypoglycemics
      have been avoided because of the assumption that their placental transfer may
      cause fetal-neonatal hypoglycemia. A recent randomized trial could not show
      measurable glyburide levels in umbilical blood despite maternal treatment with
      regular doses of glyburide. The mechanism underlying this phenomenon is not
      known. The objective of our study was to document, using a human placenta
      perfusion model, whether glyburide is actively effluxed from the fetal to the
      maternal circulation. STUDY DESIGN: In vitro perfusion studies of human cotyledon
      were performed to quantify placental transfer of glyburide. Using close circle
      experiments and introducing glyburide to both maternal and fetal circulations at
      200 ng/mL, we looked for evidence of transport against concentration gradient
      from the fetus to the mother. In parallel experiments, the P-glycoprotein
      inhibitor verapamil was used in an attempt to inhibit transplacental glyburide
      movement. RESULTS: There was highly significant transfer of glyburide against
      concentration gradient from the fetal to the maternal circulation. Fetal-to
      maternal concentration ratio was 0.92 +/- 0.23 at the start of the experimental
      period and 0.31 +/- 0.47 3 hours later (P = .01) (n = 5). Verapamil did not
      modify glyburide transport. CONCLUSION: This is the first direct evidence of
      active glyburide transport from the fetus to the mother and, in general, of any
      medicinal drug used during pregnancy. These experiments suggest that glyburide is
      actively efflux by a transporter other than P-glycoprotein. Alternatively, it is
      possible that a minority of glyburide is carried by P-glycoprotein, but most of
      the fetal load is pumped to the mother by a yet-unidentified placental transport
      system.

PMID- 16579927
TI  - Accurate prediction of fetal macrosomia using combination methods.

PMID- 16579929
TI  - Cesarean section and transient tachypnea of the newborn.

PMID- 16579930
TI  - Comparison of autologous rectus fascia and cadaveric fascia in pubovaginal sling
      continence outcomes.
AB  - OBJECTIVE: The purpose of this study was to compare autologous versus cadaveric
      grafts in pubovaginal slings. STUDY DESIGN: Women who had pubovaginal slings from
      1994 to 2003 completed history, questionnaires, prolapse staging, and cough
      stress testing. Failure was defined by recurrent urinary incontinence symptoms
      and reoperation for stress incontinence. Group differences were evaluated using
      Student t test or chi-square test. The log-rank test was used to evaluate time to
      failure between the groups. RESULTS: Of 303 women enrolled, 153 had autologous
      and 150 had cadaveric grafts. Regular urine leakage (39.6% vs 28.3%, P = .04) and
      reoperation for stress incontinence (12.7% vs 3.3%, P = .003) occurred more in
      the cadaveric versus autologous group, respectively. Adjusting for differing
      follow-up times, the cadaveric versus autologous group experienced higher rates
      of urinary incontinence (16 vs 5 per 100 women-years, P < .0001) and higher rates
      of reoperation (4 vs 1 per 100 women-years, P < .0003). CONCLUSION: Autologous
      grafts used in pubovaginal slings have superior continence outcomes compared with
      cadaveric fascia.

PMID- 16579932
TI  - Anal sphincter defects and bowel symptoms in women with and without recognized
      anal sphincter trauma.
AB  - OBJECTIVE: The purpose of this study was to determine the rate of new bowel
      symptoms and anal sphincter defects in primiparous women with and without
      recognized anal sphincter (AS) injury. STUDY DESIGN: One hundred seventeen
      primiparous women classified with increasing degrees of perineal trauma and 21
      controls delivered by cesarean section were enrolled immediately postpartum and
      demographic and delivery data were collected. At 6 weeks' postpartum, subjects
      completed a bowel function questionnaire and endoanal ultrasonography was
      performed. Logistic regression, chi-square, and 2-sample t tests were used for
      statistical analysis. RESULTS: A significant difference in new bowel symptoms was
      reported in women with (39%) and without (11%) recognized AS injury (P = .002).
      AS defects were present in 0%, 15%, 23%, 37%, and 67% of women with C/S, first-,
      second-, third-, and fourth-degree lacerations, respectively. Combined defects of
      the internal and external AS were associated with the greatest risk of new bowel
      symptoms (OR 32.1 [95% CI 9.6-107], P < .001). CONCLUSION: In women with and
      without recognized AS trauma, new bowel symptoms were strongly correlated with
      the presence of anatomic AS defects postpartum.

PMID- 16579933
TI  - The relationship between anterior and apical compartment support.
AB  - OBJECTIVE: The purpose of this study was to determine whether the degree of
      anterior compartment (bladder) and apical compartment (cervix) prolapse are
      correlated, and whether 2 anterior compartment elements (urethra and bladder) are
      related at maximal Valsalva. STUDY DESIGN: Women with a complete spectrum of
      pelvic support were recruited for a pelvic support study. Dynamic magnetic
      resonance scans were taken during Valsalva. A convenience sample of 153 women
      with a mean age of 53.3 +/- 12.5 (SD) years with a uterus in situ was studied.
      Anterior compartment status was assessed by the most caudal bladder point and the
      internal urinary meatus. The external cervical os was used to assess the apical
      compartment. The position of the bladder, urethra, and uterus were determined in
      20 nulliparous women to determine their reference locations. The distances of
      each structure below the reference positions were calculated at maximum Valsalva.
      RESULTS: Average distances of the bladder base, urethra, and uterus from the
      reference positions at maximal Valsalva were 4.1 +/- 2.4 cm, 3.1 +/- 1.3 cm, and
      4.3 +/- 2.4 cm, respectively. The Pearson correlation coefficient of the
      relationship between the bladder base and uterine distances was r = 0.73 (r2 =
      0.53). The Pearson correlation coefficient of the bladder distance and urethral
      distance was r = 0.82 (r2 = 0.67). CONCLUSION: Half of the observed variation in
      anterior compartment support may be explained by apical support.

PMID- 16579934
TI  - Childbirth and pelvic floor dysfunction: an epidemiologic approach to the
      assessment of prevention opportunities at delivery.
AB  - Female pelvic floor dysfunction is integral to the woman's role in the
      reproductive process, largely because of the unique anatomic features that
      facilitate vaginal birth and also because of the trauma that can occur during
      that event. Interventions such as primary elective cesarean delivery have been
      discussed for the primary prevention of pelvic floor dysfunction; however,
      existing data about potentially causal factors limit our ability to evaluate such
      strategies critically. Here we consider the conceptual principles of
      epidemiologic function and the availability of data that are necessary to make
      informed recommendations about prevention opportunities for pelvic floor
      dysfunction at delivery. Available epidemiologic data on pelvic floor dysfunction
      suggest that there may be substantial opportunities for the primary prevention of
      pelvic organ prolapse at delivery. Although definitive recommendations await
      further epidemiologic studies of the potential risk and benefits of obstetric
      practice change, it is hoped that this discussion will provide a novel,
      quantitative framework for the assessment of pelvic floor dysfunction prevention
      opportunities.

PMID- 16579935
TI  - Characteristics and treatment of hepatic rupture caused by HELLP syndrome.
AB  - OBJECTIVE: The purpose of this study was to review the management of hepatic
      rupture caused by HELLP (hemolysis, elevated liver enzymes, and low platelet
      count) syndrome and to assess maternal and perinatal outcomes of these cases.
      STUDY DESIGN: A retrospective study of HELLP syndrome cases that were complicated
      by hepatic rupture was conducted. RESULTS: Ten cases of hepatic rupture were
      identified. The median maternal age was 42.5 +/- 5.9 years (median +/- SD), and
      the median gestational age at delivery was 35.5 +/- 4.9 weeks. The most frequent
      signs and symptoms of hepatic rupture were the sudden onset of abdominal pain,
      acute anemia, and hypotension. Laboratory findings included low platelet count
      and increased hepatic enzymes. Surgery was performed in 9 cases. One case was
      treated nonsurgically. The maternal mortality rate was 10%, and the perinatal
      mortality rate was 80%. CONCLUSION: A combination of surgical treatment with
      hepatic artery ligation and omental patching with supportive measures was
      effective in decreasing the mortality rate in hepatic rupture caused by HELLP
      syndrome.

PMID- 16579936
TI  - Endothelin and platelet-activating factor: significance in the pathophysiology of
      ischemia/reperfusion-induced fetal growth restriction in the rat.
AB  - OBJECTIVE: The objective of the study was to evaluate the role of endothelin-1
      and platelet-activating factor in ischemia/reperfusion-induced fetal growth
      restriction in the rat. STUDY DESIGN: On day 17 of gestation, the right uterine
      and ovarian arteries were occluded for 30 minutes in experimental but not sham
      operated rats. All rats received endothelin receptor A antagonist, A-127722 (10
      mg/kg per day), platelet-activating factor antagonist, WEB-2086 (1 mg/kg), or
      vehicle. On gestational day 21, litter size, fetal viability, and fetal and
      placental weights were recorded. Reverse transcription-polymerase chain reaction
      for phospholipase A2-IIA and preproendothelin-1 messenger ribonucleic acid was
      performed on uterus and placentas from each uterine horn. Groups were compared
      statistically by analysis of variance. RESULTS: Ischemia/reperfusion reduced
      fetal weights, in both the ischemic horn and the nonischemic horn (P < .001).
      Antagonism of either endothelin receptor A or platelet-activating factor
      normalized fetal growth in both horns. Neither placental weight nor the incidence
      of fetal demise was affected by ischemia/reperfusion. Phospholipase A2-IIA and
      preproendothelin-1 messenger ribonucleic acid expression did not differ between
      right and left uterine horns in any group. Uterine and placental tissues in the
      ischemia/reperfusion group exhibited increased phospholipase A2-IIA (P < .01) but
      not preproendothelin-1. CONCLUSION: Endothelin-1 and platelet-activating factor
      are both important mediators in the pathophysiology of ischemia/reperfusion
      induced fetal growth restriction in the rat, contributing to the fetal growth
      restriction observed in both the ischemic and nonischemic horns. Antagonism of
      either mediator produces normal fetal growth in this model of fetal growth
      restriction.

PMID- 16579937
TI  - Annexin A5 levels in midtrimester amniotic fluid: association with intrauterine
      growth restriction.
AB  - OBJECTIVE: The purpose of this study was to determine whether amniotic fluid
      levels of annexin A5 (AF-AnxA5) may be associated with intrauterine growth
      restriction (IUGR). STUDY DESIGN: Amniotic fluid was obtained in a cohort of
      pregnant patients (n = 172) undergoing amniocentesis at 15 to 24 weeks' gestation
      and annexin A5 (AnxA5) levels were determined with enzyme-linked immunosorbent
      assay (ELISA). Patients who developed IUGR were compared with the remainder of
      the cohort. RESULTS: AF-AnxA5 levels significantly increased through gestation (P
      = .003). The mean level of AF-AnxA5 in IUGR patients (n = 15) was significantly
      higher (P = .028) than in the remainder of the cohort (n = 130). Elevated AF
      AnxA5 > 20 ng/mL was associated with a relative risk of 3.5 for the development
      of IUGR (P = .023). CONCLUSION: AnxA5 is present in amniotic fluid and increases
      through gestation from 15 to 24 weeks. Elevated AF-AnxA5 levels were present in
      patients who developed IUGR. AF-AnxA5 may be a useful marker for identifying
      pregnancy abnormalities.

PMID- 16579938
TI  - Circulating tumor DNA as a prognostic factor.

PMID- 16579939
TI  - Artificial intelligence: can computers help solve the puzzle of parturition?

PMID- 16579940
TI  - Levator plate angle in women with pelvic organ prolapse compared to women with
      normal support using dynamic MR imaging.
AB  - OBJECTIVE: The purpose of this study was to determine whether the levator plate
      is (1) horizontal in women with normal support, (2) different between women with
      and without prolapse, (3) related to levator hiatus and perineal body descent.
      STUDY DESIGN: Cohorts of cases with prolapse at least 1 cm below the hymen and
      normal controls with all points 1 cm or more above the hymen were prospectively
      enrolled in a study of pelvic organ support to be of similar age, race, and
      parity. Subjects underwent supine midsagittal dynamic magnetic resonance imaging
      (MRI) during Valsalva. Levator plate angle (LPA) was measured relative to a
      horizontal reference line. Levator hiatus length (LH) and perineal body location
      (PB) were also measured. Student t tests and Pearson correlation coefficients (r)
      were performed. RESULTS: Sixty-eight controls and 74 cases were analyzed. During
      Valsalva, controls had a mean LPA of 44.3 degrees . Cases, compared to controls,
      had 9.1 degrees (21%) more caudally directed LPA (53.4 degrees vs 44.3 degrees ,
      P < .01), 15% larger LH length (7.8 cm vs 6.8 cm, P < .01), and 24% more caudal
      PB location (6.8 cm vs 5.5 cm, P < .01). Increases in LPA were correlated with
      increased LH length (r = 0.42, P < .0001) and PB location (r =.51, P < .0001).
      CONCLUSION: The measured levator plate angle in women with normal support is 44.3
      degrees . During Valsalva, women with prolapse have a modest (9.1 degrees) though
      statistically greater levator plate angle compared to controls. This larger angle
      showed moderate correlation with larger levator hiatus length and greater
      displacement of the perineal body in women with prolapse compared to controls.

PMID- 16579942
TI  - Posterior vaginal sling experience in elderly patients yields poor results.
AB  - OBJECTIVE: The objective of the study was to evaluate our experience with the
      posterior vaginal sling in an elderly population. STUDY DESIGN: Elderly patients
      with significant vaginal prolapse underwent a posterior vaginal sling using the
      IVS Tunneller device (Tyco Healthcare, United States Surgical, Norwalk, CT).
      Primary failure was defined as a postoperative pelvic organ prolapse quantitative
      point C (the apex of the vagina) within 2 cm of the preoperative value. Secondary
      failure was defined as any portion of the anterior or posterior vaginal walls
      protruding to or beyond the hymeneal ring (pelvic organ prolapse quantitative
      points Aa or Ap equal to or greater than 0). RESULTS: Twenty-one patients
      underwent the procedure; 19 were seen for follow up. The average age was 70 years
      (range 60-78). Twelve patients had primary or secondary failures (12 of 19, 63%).
      There were 5 primary failures (5 of 19, 26%) and 7 secondary failures (7 of 19,
      37%). The mean time to failure was 7 weeks (range 1-18). CONCLUSION: In our
      elderly population, the posterior vaginal sling has a high failure rate,
      occurring early in the postoperative period.

PMID- 16579943
TI  - Microscopic hematuria as a predictive factor for detecting bladder cancer at
      cystoscopy in women with irritative voiding symptoms.
AB  - OBJECTIVE: The purpose of this study was to assess microscopic hematuria as a
      predictive factor for detecting bladder cancer at cystoscopy in women with
      irritative voiding symptoms. STUDY DESIGN: We conducted a retrospective cohort
      analysis of women with irritative voiding symptoms who presented for urodynamic
      testing and cystoscopy. Irritative voiding symptoms were defined as urgency, urge
      incontinence, frequency, dysuria, and/or nocturia. Patient demographics, risk
      factors for bladder cancer, presence of microscopic hematuria, urodynamic
      findings, and cystoscopy and biopsy results were recorded. RESULTS: Of 735
      patients with irritative voiding symptoms, 264 (35.9%) had microscopic hematuria
      and 471 (64.1%) had no hematuria. Bladder cancer was detected in 3 women, for an
      overall detection rate of 0.4%. Microscopic hematuria, urgency, frequency,
      dysuria, nocturia, age, and tobacco use were not significantly associated with
      bladder cancer. CONCLUSION: In this cohort of women with irritative voiding
      symptoms, microscopic hematuria was not predictive for bladder cancer.

PMID- 16579944
TI  - Nocturic frequency is related to severity of obstructive sleep apnea, improves
      with continuous positive airways treatment.
AB  - OBJECTIVE: The purpose of this study was to determine the relationship between
      nocturia and obstructive sleep apnea (OSA), and the effect of continuous positive
      airways pressure (CPAP) therapy on nocturic frequency. STUDY DESIGN: This was a
      retrospective review of sleep studies including patients with and without
      evidence of OSA, before and during CPAP treatment (where relevant). Chi-squared
      tests compared nocturia prevalence according to sleep diagnosis, logistic
      regression determined predictors of nocturia, and regression analyses determined
      predictors of nocturic frequency. RESULTS: In 196 eligible studies, predictors of
      nocturia included increasing age and diabetes mellitus; nocturia was equally
      likely to occur in patients with and without OSA. In patients with OSA and
      nocturia, nocturic frequency was related to age, diabetes, and severity of OSA (P
      < .001). Patients with OSA and nocturia who were treated with CPAP demonstrated a
      significant decrease in nocturic frequency (P < .001). CONCLUSION: OSA severity
      predicts nocturic frequency. The role of testing in the triage of patients with
      nocturia remains to be determined.

PMID- 16579946
TI  - Neonatal mortality and morbidity rates in term twins with advancing gestational
      age.
AB  - OBJECTIVE: The purpose of this study was to identify the gestational age with the
      lowest morbidity and mortality rates for twin pregnancies that reach term. STUDY
      DESIGN: A retrospective cohort study carried out with 60,443 twin pairs from the
      United States (1995-1997). Analysis was restricted to pregnancies that had
      reached at least 37 weeks of gestation; groups were created on the basis of the
      gestational ages of 37, 38, 39, and > or = 40 weeks. The incidence of death and
      morbidity were calculated; multiple logistic regression models were used to
      estimate the independent effect of gestational age for twin A and B. RESULTS: The
      neonatal mortality rate increased significantly after 40 weeks of gestation (twin
      A: odds ratio, 3.47 [95% CI, 2.29, 5.38]; twin B, odds ratio, 2.52 [95% CI, 1.75,
      3.67]). There was also an increased risk of neonatal morbidity in the > or = 40
      weeks of gestation group for twin A and B (Apgar score, < or = 3; odds ratio,
      1.88 [95% CI, 1.18, 3.02], 1.74 [95% CI, 1.21, 2.52], respectively). There was a
      decreased risk of assisted ventilation in the 38 and 39 weeks of gestation group
      for twin A (odds ratio, 0.86 [95% CI, 0.77, 0.97], odds ratio, 0.83 [95% CI,
      0.72, 0.95], respectively) and a decreased risk in the 39 and > or = 40 weeks of
      gestation groups for twin B (assisted ventilation: odds ratio, 0.83 [95% CI,
      0.73, 0.93], odds ratio, 0.81 [95% CI, 0.72, 0.92], respectively). CONCLUSION:
      This study suggests that the optimal date of delivery for twins should be <40
      weeks of gestation; there was no compelling evidence for delivering at <38 weeks
      of gestation.

PMID- 16579947
TI  - Neurodevelopmental outcome after laser therapy for twin-twin transfusion
      syndrome.

PMID- 16579948
TI  - Is vitamin E a safe prophylaxis for preeclampsia?
AB  - The prophylactic use of vitamins E and C for the prevention of preeclampsia is
      currently being evaluated in multiple clinical trials in Canada, Mexico, the
      United Kingdom, the United States, and other developing countries. In addition to
      its antioxidant capacity, exogenous vitamin E may prevent an immunologic switch
      (Th1 to Th2) that is vital for early-to late transition in normal pregnancies.
      Moreover, vitamin E could be a potential interferon-gamma (IFN-gamma) mimic
      facilitating persistent proinflammatory reactions at the fetal-maternal
      interface. These untoward effects of dietary intake of vitamin E may be more
      pronounced in those treated cases that fail to develop preeclampsia. A critical
      test of this hypothesis would be to establish whether, under variable O2 tension,
      vitamin E is capable of affecting cytokine signaling in placental trophoblasts
      and maternal immune effector cells, both in early and late human pregnancies.

PMID- 16579949
TI  - Comparison of glyburide and insulin for the management of gestational diabetes in
      a large managed care organization.

PMID- 16579950
TI  - The risk of hydrosalpinx formation and adnexectomy following tubal ligation and
      subsequent hysterectomy: a historical cohort study.
AB  - OBJECTIVE: The objective of the study was to further investigate a previous
      finding that tubal sterilization followed by hysterectomy was associated with
      hydrosalpinx formation. STUDY DESIGN: The Rochester Epidemiology Project
      (Rochester, MN) was used to identify three cohorts: women who had undergone tubal
      sterilization and subsequent hysterectomy, women who had undergone tubal
      sterilization alone, and women who had undergone hysterectomy alone. Four hundred
      seventy-three charts were reviewed and 337 met inclusion criteria. Patient
      histories were analyzed prospectively, looking for subsequent adnexal surgery.
      RESULTS: There was no increased risk of hydrosalpinx formation in patients who
      had undergone tubal sterilization and hysterectomy, compared with tubal
      sterilization alone. The proportion of subjects undergoing later adnexectomy for
      any reason was significantly higher in the hysterectomy groups, compared with the
      sterilization only group (relative risk 3.5, 95% confidence interval 1.3-9.4).
      CONCLUSION: This prospective study does not support the previously reported case
      control data suggesting that tubal sterilization followed by hysterectomy
      resulted in an increased risk of hydrosalpinx formation, compared with tubal
      sterilization alone.

PMID- 16579951
TI  - Nondisruptive, sequence-specific coupling of fluorochromes to plasmid DNA.
AB  - A method to attach a fluorochrome sequence-specifically to supercoiled plasmid
      DNA (pDNA) without perturbing transgene expression would provide an invaluable
      aid in a variety of applications requiring probes for the intracellular tracking
      of transfected pDNA. Here we report a method to couple commercially available
      fluorochromes covalently and sequence-specifically to pDNA using a peptide
      nucleic acid (PNA) as a linker molecule. The terminal cysteine thiol group on the
      PNA peptide backbone is reacted with a maleimide moiety on the fluorochrome to
      produce a fluorescent conjugate which is in turn hybridized to a plasmid
      expression vector containing an 11-bp target sequence. Spectroscopic evaluation
      and an electrophoretic mobility shift assay showed that the pDNA hybridized to
      one PNA-fluorochrome conjugate molecule. The fluorescence signal comigrated with
      pDNA on acrylamide gels, confirming the stable attachment of the fluorescent
      conjugate to the pDNA. The utility of one of the conjugates, PNA-Oregon green
      488/pCMVbeta-DTS, to probe pDNA transport across the nuclear envelope, a
      significant barrier to gene transfer, was undertaken using a digitonin
      permeabilized HeLa cell assay. The PNA-Oregon green 488/pCMVbeta-DTS conjugate is
      able to efficiently traverse the nuclear membrane of the permeabilized cells,
      accumulating in the nuclei within 30 min and reaching maximal levels by 1h. When
      transfected into HeLa cells, the PNA-Oregon green 488/pCMVbeta-DTS conjugate
      retained 55% of the native plasmid's biological activity, as determined by a beta
      galactosidase assay. Thus, this method allows for the sequence-specific coupling
      of commercially available fluorochromes to DNA expression vectors while retaining
      biological function.

PMID- 16579952
TI  - Assessment of knife sharpness by means of a cutting force measuring system.
AB  - Following a brief description of the problem of musculoskeletal disorders (MSDs)
      in the meat industry and use of knives, this paper presents a study of the
      influence of the main intrinsic technical characteristics of a knife on its
      cutting performance. This study prompted design of a specific system for
      measuring initial cutting capacity and cutting edge retention. This design
      process preceded research into test conditions (cutting speed, sample nature and
      thickness, knife inclination angle, etc.) offering optimum test bench operation.
      This equipment was then used to study the influence of blade inclination angle,
      steel grade and sharpening angle on cutting performance. It has been shown that
      cutting force varies with blade inclination. Use of knives with curved blades
      and/or a blade inclined with respect to the knife handle is therefore preferred
      in relation to our cutting force reduction objective. It has also been shown that
      choices are in fact governed by compromises in relation to other parameters
      (steel grade and edge angle). These observations confirm the need to set up
      suitable training of knife users to achieve best possible cutting performance.

PMID- 16579953
TI  - Inflammatory cytokines induce protein tyrosine nitration in rat astrocytes.
AB  - Protein tyrosine nitration may be relevant for the pathogenesis of hepatic
      encephalopathy (HE). Infections, sepsis, and trauma precipitate HE episodes.
      Recently, serum levels of tumor necrosis factor (TNF)-alpha were shown to
      correlate with severity of HE in chronic liver failure. Here the effects of
      inflammatory cytokines on protein tyrosine nitration in cultured rat astrocytes
      and rat brain in vivo were studied. In cultured rat astrocytes TNF-alpha (50
      pg/ml-10 ng/ml) within 6h increased protein tyrosine nitration. TNF-alpha-induced
      tyrosine nitration was related to an increased formation of reactive oxygen and
      nitrogen intermediates, which was downstream from a NMDA-receptor-dependent
      increase of intracellular [Ca(2+)](i) and nNOS-catalyzed NO production.
      Astroglial tyrosine nitration was also elevated in brains of rats receiving a non
      lethal injection of lipopolysaccharide, as indicated by colocalization of
      nitrotyrosine immunoreactivity with glial fibrillary acidic protein and glutamine
      synthetase, and by identification of the glutamine synthetase among the tyrosine
      nitrated proteins. It is concluded that reactive oxygen and nitrogen
      intermediates as well as protein tyrosine nitration by inflammatory cytokines may
      alter astrocyte function in an NMDA-receptor-, Ca(2+)-, and NOS-dependent
      fashion. This may be relevant for the pathogenesis of HE and other conditions
      involving cytokine exposure the brain.

PMID- 16579954
TI  - Influence of glutathione fructosylation on its properties.
AB  - Incubation of fructose and glutathione leads to the formation of N-2-deoxy-glucos
      2-yl glutathione as the major glycation product, with characteristic positive ion
      at 470 Th in LC-MS spectra. Glutathione disulfide and fructose generate two
      compounds: N-2-deoxy-glucos-2-yl glutathione disulfide (m/z=775 Th) and bis di
      N,N'-2-deoxy-glucos-2-yl glutathione disulfide (m/z=937 Th). N-2-deoxy-glucos-2
      yl glutathione is 2.5-fold less effective than glutathione in reducing
      dehydroascorbic acid. Glutathione peroxidase and glutahione-S-transferase exhibit
      marginal activity toward N-2-deoxy-glucos-2-yl glutathione, while glyoxalase I
      shows 44.9% of the enzyme's specific activity. Glutathione reductase demonstrates
      6.9% of the enzyme's specific activity with bis di-N,N'-2-deoxy-glucos-2-yl
      glutathione, while with mono-N-glucosyl glutathione disulfide retained 5 6.1% of
      the original activity. Glutathione reductase could not reduce N-2-deoxy-glucos-2
      yl glutathione in mixed disulfide with gammaS-crystallin, but reduced glutathione
      in mixed disulfide with gammaS-crystallin by 90%. The presence of N-2-deoxy
      glucos-2-yl glutathione in mixed disulfide with gammaS-crystallin makes this
      molecule more susceptible to unfolding than native gammaS-crystallin.

PMID- 16579955
TI  - Bovine factor B: cloning, expression, and characterization.
AB  - Bovine factor B, a polypeptide required for the coupled activity of the
      mitochondrial ATP synthase complex, was cloned. A novel expression system for
      overproducing the recombinant bovine factor B was developed, which yielded the
      recombinant polypeptide at a level of 12-15 mg of protein per liter of bacterial
      culture. Reconstitution of the recombinant polypeptide with factor B-depleted
      ammonia, EDTA-treated submitochondrial particles (AE-SMP) restored the formation
      of substrate-driven DeltapH gradient across vesicular membranes, presumably by
      blocking a proton leak. The proton leak in the AE-SMP could also be blocked by
      the F0 inhibitors oligomycin and dicyclohexylcarbodiimide, but not the F1-ATPase
      inhibitors efrapeptin and aurovertin B. The six factor B thiols titrated rapidly
      with Ellman's reagent, and two of these, presumably Cys92 and Cys94, gained
      protection following treatment of factor B with a vicinal dithiol-specific
      reagent phenylarsine oxide (PAO). Similarly, Cd2+, whose binding to factor B is
      believed to also involve a vicinal dithiol, and PAO, protected approximately 2
      Cys residues against labeling with sulfhydryl-specific fluorescent reagent
      fluorescein-5'-maleimide. The circular dichroism spectra showed that binding of
      Cd2+ and Zn2+, but not Ca2+ to bovine factor B caused small but reproducible
      changes in the secondary structure elements of the polypeptide.

PMID- 16579956
TI  - The effect of tocopheryl phosphates on atherosclerosis progression in rabbits fed
      with a high cholesterol diet.
AB  - The effect of tocopheryl phosphate on atherosclerosis progression has been
      studied in rabbits, fed with a 2% cholesterol diet and compared with an
      equivalent amount of alpha-tocopheryl acetate. The results show that the
      atherosclerotic-preventing effect of the phosphate derivative was more pronounced
      than that of the acetate derivative. alpha-Tocopheryl phosphate was also more
      potent in diminishing the expression of CD36 than the acetate derivative.

PMID- 16579957
TI  - Low resolution structure and stability studies of human GrpE#2, a mitochondrial
      nucleotide exchange factor.
AB  - GrpE acts as a nucleotide exchange factor for the Hsp70 chaperone system. Only
      one GrpE isoform is present in Escherichia coli, but for reasons not yet well
      understood, two GrpE isoforms have been found in mammalian
      mitochondria.Therefore, studies aimed at evaluating the physico-chemical
      characteristics of these proteins are important for the comprehension of the
      function of the Hsp70 chaperone system in different organisms. Here we report
      biophysical studies on human mitochondrial GrpE isoform 2. Small angle X-ray
      scattering measurements of human GrpE isoform 2 showed that this protein has a
      quaternary structure which is similar to those of human GrpE isoform 1 and E.
      coli GrpE: a dimer with a cruciform elongated shape. However, mitochondrial
      isoforms differed from each other regarding chemical and thermal denaturation
      profiles. This fact, combined with results of distinct expression patterns
      previously reported, point out that these proteins may have different response to
      external stimuli. Our results also indicate that human GrpE isoform 2 is more
      similar to the GrpE from E. coli than to human GrpE isoform 1. These results are
      relevant because differences in the conformation of Hsp70 co-chaperones are
      considered to be one of the reasons for functional diversity of this system.

PMID- 16579958
TI  - Isoprenoid biosynthesis in Artemisia annua: cloning and heterologous expression
      of a germacrene A synthase from a glandular trichome cDNA library.
AB  - Artemisia annua (Asteraceae) is the source of the anti-malarial compound
      artemisinin. To elucidate the biosynthetic pathway and to isolate and
      characterize genes involved in the biosynthesis of terpenoids including
      artemisinin in A. annua, glandular trichomes were used as an enriched source for
      biochemical and molecular biological studies. The sequencing of 900 randomly
      selected clones from a glandular trichome plasmid cDNA library revealed the
      presence of many ESTs involved in isoprenoid biosynthesis such as enzymes from
      the methylerythritol phosphate pathway and the mevalonate pathway, amorpha-4,11
      diene synthase and other sesquiterpene synthases, monoterpene synthases and two
      cDNAs showing high similarity to germacrene A synthases. Full-length sequencing
      of the latter two ESTs resulted in a 1686-bp ORF encoding a protein of 562 aa.
      Upon expression in Escherichia coli, the recombinant protein was inactive with
      geranyl diphosphate, but catalyzed the cyclization of farnesyl diphosphate to
      germacrene A. These results demonstrate the potential of the use of A. annua
      glandular trichomes as a starting material for studying isoprenoid biosynthesis
      in this plant species.

PMID- 16579959
TI  - Catalytic subunit of cAMP-dependent protein kinase from a catch muscle of the
      bivalve mollusk Mytilus galloprovincialis: purification, characterization, and
      phosphorylation of muscle proteins.
AB  - cAMP-dependent protein kinase (PKA) plays a crucial role in the release of the
      catch state of molluskan muscles, but the nature of the enzyme in such tissues is
      unknown. In this paper, we report the purification of the catalytic (C) subunit
      of PKA from the posterior adductor muscle (PAM) of the sea mussel Mytilus
      galloprovincialis. It is a monomeric protein with an apparent molecular mass of
      40.0+/-2.0kDa and Stoke's radius 25.1+/-0.3A. The protein kinase activity of the
      purified enzyme was inhibited by both isoforms of the PKA regulatory (R) subunit
      that we had previously characterized in the mollusk, and also by the inhibitor
      peptide PKI(5-24). On the other hand, the main proteins of the contractile
      apparatus of PAM were partially purified and their ability to be phosphorylated
      in vitro by purified PKA C subunit was analyzed. The results showed that
      twitchin, a high molecular mass protein associated with thick filaments, was the
      better substrate for endogenous PKA. It was rapidly phosphorylated with a
      stoichiometry of 3.47+/-0.24mol Pmol(-1) protein. Also, catchin, paramyosin, and
      actin were phosphorylated, although more slowly and to a lesser extent. On the
      contrary, myosin heavy chain (MHC) and tropomyosin were not phosphorylated under
      the conditions used.

PMID- 16579960
TI  - Cell selectivity correlates with membrane-specific interactions: a case study on
      the antimicrobial peptide G15 derived from granulysin.
AB  - A 15-residue peptide dimer G15 derived from the cell lytic protein granulysin has
      been shown to exert potent activity against microbes, including E. coli, but not
      against human Jurkat cells [Z. Wang, E. Choice, A. Kaspar, D. Hanson, S. Okada,
      S.C. Lyu, A.M. Krensky, C. Clayberger, Bactericidal and tumoricidal activities of
      synthetic peptides derived from granulysin. J. Immunol. 165 (2000) 1486-1490]. We
      investigated the target membrane selectivity of G15 using fluorescence, circular
      dichroism and 31P NMR methods. The ANS uptake assay shows that the extent of E.
      coli outer membrane disruption depends on G15 concentration. 31P NMR spectra
      obtained from E. coli total lipid bilayers incorporated with G15 show disruption
      of lipid bilayers. Fluorescence binding studies on the interaction of G15 with
      synthetic liposomes formed of E. coli lipids suggest a tight binding of the
      peptide at the membrane interface. The peptide also binds to negatively charged
      POPC/POPG (3:1) lipid vesicles but fails to insert deep into the membrane
      interior. These results are supported by the peptide-induced changes in the
      measured isotropic chemical shift and T1 values of POPG in 3:1 POPC:POPG
      multilamellar vesicles while neither a non-lamellar phase nor a fragmentation of
      bilayers was observed from NMR studies. The circular dichroism studies reveal
      that the peptide exists as a random coil in solution but folds into a less
      ordered conformation upon binding to POPC/POPG (3:1) vesicles. However, G15 does
      not bind to lipid vesicles made of POPC/POPG/Chl (9:1:1) mixture, mimicking tumor
      cell membrane. These results explain the susceptibility of E. coli and the
      resistance of human Jurkat cells to G15, and may have implications in designing
      membrane-selective therapeutic agents.

PMID- 16579962
TI  - Aquaporin subfamily with unusual NPA boxes.
AB  - Aquaporins have been identified based on highly conserved two asparagine-proline
      alanine (NPA) boxes that are important for the formation of a water-permeating
      pore. Some aquaporin-like sequences, however, have less conserved NPA boxes.
      Although they have lower homology with conventional aquaporins, they should be
      included in aquaporin family based on their conserved six transmembrane domains
      and hydrophobic NPA box-like repeats. They are widely distributed in
      multicellular organisms. Only SIPs from plants and AQP11/12 from mammals were
      examined previously and found to be localized inside the cell. Intracellular
      localization will be a common feature of these aquaporin-like proteins since most
      of them have positively charged amino acid clusters at the carboxy-termini
      similar to di-lysine motif (-KKXX) for an endoplasmic reticulum retention signal.
      Accordingly, they are tentatively named subcellular-aquaporins in this review.
      Currently, studies on their functions and biological roles are limited. SIPs were
      shown to function as water channels and the disruption of AQP11 produced
      neonatally fatal polycystic kidneys. Further works on subcellular-aquaporins will
      reveal new insights into the roles of aquaporins.

PMID- 16579961
TI  - Biophysical studies of the interactions between 14-mer and 21-mer model
      amphipathic peptides and membranes: insights on their modes of action.
AB  - We have investigated the interactions between synthetic amphipathic peptides and
      zwitterionic model membranes. Peptides with 14 and 21 amino acids composed of
      leucines and phenylalanines modified by the addition of crown ethers have been
      synthesized. The 14-mer and 21-mer peptides both possess a helical amphipathic
      structure as revealed by circular dichroism. To shed light on their mechanism of
      membrane interaction, different complementary biophysical techniques have been
      used such as circular dichroism, fluorescence, membrane conductivity measurement
      and NMR spectroscopy. Results obtained by these different techniques show that
      the 14-mer peptide is a membrane perturbator that facilitate the leakage of
      species such as calcein and Na ions, while the 21-mer peptide acts as an ion
      channel. (31)P solid-state NMR experiments on multilamellar vesicles reveal that
      the dynamics and/or orientation of the polar headgroups are greatly affected by
      the presence of the peptides. Similar results have also been obtained in
      mechanically oriented DLPC and DMPC bilayers where different acyl chain lengths
      seem to play a role in the interaction. On the other hand, (2)H NMR experiments
      on multilamellar vesicles demonstrate that the acyl chain order is affected
      differently by the two peptides. Based on these studies, mechanisms of action are
      proposed for the 14-mer and 21-mer peptides with zwitterionic membranes.

PMID- 16579963
TI  - Detergent solubilization of phosphatidylcholine bilayers in the fluid state:
      influence of the acyl chain structure.
AB  - Seventeen different, chemically defined phosphatidylcholines, dispersed in
      aqueous medium in the form of large unilamellar vesicles, have been tested for
      solubilization by the non-ionic detergent Triton X-100. The temperatures (either
      20 degrees C or 45 degrees C) were such that the bilayers were always in the
      liquid-disordered state. For each case, the solubilization parameters, Don (total
      detergent: lipid mole ratio producing the onset of solubilization) and D50 (total
      detergent: lipid mole ratio producing 50% solubilization), were determined under
      equilibrium conditions. Both parameters varied generally in parallel. When double
      bonds were introduced to the acyl chains, other factors remaining constant,
      solubilization became more difficult, i.e., more detergent was required. Cis
      unsaturated phospholipids required more detergent than the corresponding trans
      isomers. Increasing chain length in saturated phospholipids between C12 and C16
      decreased moderately the detergent/lipid ratios causing solubilization. Acyl and
      alkyl phospholipids were equally susceptible to Triton X-100 solubilization.
      Lipid chain order, as measured by DPH fluorescence polarization, seemed to
      facilitate solubilization, perhaps because more ordered bilayers have a smaller
      capacity to accommodate detergent monomers without breaking down into lipid
      detergent mixed micelles.

PMID- 16579964
TI  - A modified DBT skills training program for oppositional defiant adolescents:
      promising preliminary findings.
AB  - A modified skills training component of dialectical behavior therapy (DBT) was
      implemented in a group therapy format for non-suicidal outpatient young
      adolescents who met criteria for oppositional defiant disorder (ODD). Thirty-two
      youths completed the 16-week program, as well as pre- and post-treatment
      measures. The treatment was effective not only in decreasing negative behaviors,
      but also in increasing positive behaviors, per caregiver report. The youths
      reported a significant reduction in externalizing and internalizing symptoms and
      in depression. Reliable change indices indicated that far more participants were
      in the improved category than in the deteriorated category on the measures of
      interest. Despite the absence of control groups but consistent with the treatment
      outcome research literature for DBT-based treatments for other disorders, this
      study demonstrated that DBT skills training is feasible and shows promise in
      improving the behavior of ODD young adolescents.

PMID- 16579965
TI  - Tocopherol-associated protein-1 accelerates apoptosis induced by alpha-tocopheryl
      succinate in mesothelioma cells.
AB  - Alpha-tocopheryl succinate (alpha-TOS), a redox-silent analogue of vitamin E,
      induces apoptosis in multiple cell lines in a selective manner, by activating the
      intrinsic pathway. Since it is a highly hydrophobic compound, it may require a
      carrier protein for its trafficking to intracellular targets like mitochondria.
      We studied the role of the ubiquitous tocopherol-associated protein-1 (TAP1 or
      sec14-like 2) in apoptosis induction by alpha-TOS in malignant mesothelioma (MM)
      cells. Over-expression of TAP1 in MM cells sensitised them to apoptosis by low
      doses of alpha-TOS which were sub-apoptotic for the parental cells. Apoptosis
      induced in TAP1-over-expressing cells was mitochondria- and caspase-dependent, as
      suggested by dissipation of mitochondrial trans-membrane potential and inhibition
      by zVAD-fmk, respectively. Binding assays showed affinity of alpha-TOS for TAP1.
      Finally, TAP1 over-expressing cells accumulated alpha-TOS at higher levels
      compared to their normal counterparts. We suggest that TAP1 may act as an
      intracellular shuttle for alpha-TOS, promoting apoptosis initiated by this
      vitamin E analogue, as shown here for MM cells.

PMID- 16579966
TI  - Myocardial sarcomeres spontaneously oscillate with the period of heartbeat under
      physiological conditions.
AB  - During heartbeat, the repeated contractions of myocardium are induced by the
      oscillation of intracellular Ca(2+) concentration. On the other hand, when
      intermediately activated at a certain Ca(2+) concentration, cardiac myofibrils
      exhibit the spontaneous sarcomeric oscillation (Ca-SPOC) under steady ionic
      conditions. In the present study, we found that Ca-SPOC occurred over a wide
      range of Ca(2+) concentrations, including physiological contractile conditions,
      in skinned myocardium prepared from various animal species (rat, rabbit, pig, and
      cow). The period of sarcomeric oscillation fell within the same range as the
      period of heartbeat of each animal species. On the basis of these results we
      propose that the intrinsic auto-oscillatory property of sarcomeres (myofibrils)
      significantly contributes to myocardial beating in vivo.

PMID- 16579967
TI  - JNK1 is required to preserve cardiac function in the early response to pressure
      overload.
AB  - Cardiac stress consistently activates c-Jun NH(2)-terminal kinase (JNK) pathways,
      however the role of different members of the JNK family is unclear. In this
      study, we applied pressure overload (TAC) in mice with selective deletion of the
      three JNK genes (Jnk1(-/-), Jnk2(-/-), and Jnk3(-/-)). Following TAC, all three
      JNK knockout mouse lines developed cardiac hypertrophy similar to wild-type mice
      (WT), but only JNK1(-/-) mice displayed a significant reduction in fractional
      shortening after 3 and 7 days of pressure overload, associated with a significant
      increase in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      staining and marked inflammatory infiltrate. After the acute deterioration stage,
      JNK1(-/-) mice underwent a slow recovery followed by a steady progression of
      cardiac dysfunction, becoming indistinguishable from WT after 12 weeks of TAC.
      These data suggest that JNK1 plays a protective role in response to pressure
      overload, preventing the early deterioration in cardiac function following an
      acute increase in afterload.

PMID- 16579968
TI  - The zinc chelator, N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine,
      increases the level of nonfunctional HIF-1alpha protein in normoxic cells.
AB  - The hypoxia-inducible factor-1alpha (HIF-1alpha) subunit is activated in response
      to lack of oxygen. HIF-1alpha-specific prolyl hydroxylase and factor inhibiting
      HIF-1alpha (FIH-1) catalyze hydroxylation of the proline and asparagine residues
      of HIF-1alpha, respectively. The hydroxyproline then interacts with ubiquitin E3
      ligase, the von Hippel-Lindau protein, leading to degradation of HIF-1alpha by
      ubiquitin-dependent proteasomes, while the hydroxylation of the asparagine
      residue prevents recruitment of the coactivator, cAMP-response element-binding
      protein (CBP), thereby decreasing the transactivation ability of HIF-1alpha. We
      found that the Zn-specific chelator, N,N,N',N'-tetrakis (2-pyridylmethyl)
      ethylenediamine (TPEN), enhances the activity of HIF-1alpha-proline hydroxylase 2
      but the level of HIF-1alpha protein does not fall because TPEN also inhibits
      ubiquitination. Since the Zn chelator does not prevent FIH-1 from hydroxylating
      the asparagine residue of HIF-1alpha, its presence leads to the accumulation of
      HIF-1alpha that is both prolyl and asparaginyl hydroxylated and is therefore
      nonfunctional. In hypoxic cells, TPEN also prevents HIF-1alpha from interacting
      with CBP, so reducing expression of HIF-1alpha target genes. As a result, Zn
      chelation causes the accumulation of nonfunctional HIF-1alpha protein in both
      normoxia and hypoxia.

PMID- 16579969
TI  - Melanocortin 4 receptors interact with antimicrobial frog peptide analogues.
AB  - We have developed fluorescence polarization (FP) assays of human melanocortin 4
      receptor (MC4R) in 384-well microtiter plates using TAMRA-NDP-MSH as a tracer.
      The rank order of potency of agonists and antagonists agrees well relative to the
      published assays: SHU9119>MTII>NDP alphaMSH>alphaMSH. We have screened libraries
      of Korean plant extracts and frog peptide analogues in search of MC4R ligands
      using FP assays and cell-based CRE luciferase reporter assays. We report that
      FLGFLFKVASK, FLGWLFKVASK, FLGALFKWASK, and FLGWLFKWASK are the peptide analogues,
      which bind to human MC4R receptor with good affinity in vitro. FLGWLFKVASK and
      FLGWLFKWASK stimulated CRE-driven reporter gene via MC4R. In luciferase reporter
      assays, they possess the pharmacological and functional profiles of full
      agonists. We demonstrate the interaction of MC4R with 11-residue antimicrobial
      peptides derived from the Korean frog, Rana rugosa. The results suggest that MC4R
      interacts promiscuously with bioactive analogues of antimicrobial peptide,
      gaegurin-5.

PMID- 16579970
TI  - Tertiary structure prediction of SARS coronavirus helicase.
AB  - SARS coronavirus, SCV, has been recently responsible of a sudden and widespread
      infection which caused almost 800 victims. The limited amount of SCV protein
      structural information is partially responsible of the lack of specific drugs
      against the virus. Coronavirus helicases are very conserved and peculiar proteins
      which have been proposed as suitable targets for antiviral drugs, such as
      bananins, which have been recently shown to inhibit the SCV helicase in vitro.
      Here, the quaternary structure of SCV helicase has been predicted, which will
      provide a solid foundation for the rational design of other antiviral helicase
      inhibitors.

PMID- 16579971
TI  - Regulation of human STARD4 gene expression under endoplasmic reticulum stress.
AB  - STARD4 belongs to the STARD family of proteins that have steroidogenic acute
      regulatory protein-related lipid transfer domains and function in the transport
      and metabolism of lipids. We isolated STARD4 as a novel endoplasmic reticulum
      (ER) stress-responsive gene using a subtracted, ER stress-specific human cDNA
      library, and analyzed its transcriptional regulation under ER stress. Northern
      blot analysis revealed that the induction of STARD4 by ER stress was limited to
      the early phase. Luciferase reporter assay showed that the induction of STARD4
      depended on both transcription factor ATF6 and an ERSE-like element in its
      promoter. To date, no other genes that are induced only during the early phase of
      ER stress have been identified, although the mammalian ER stress response is
      known to be regulated multiphasically and to induce expression of other genes.
      This study is a first step in elucidating the relationship between lipid
      metabolism and the ER stress response.

PMID- 16579972
TI  - The antifibrotic effect of TGF-beta1 siRNAs in murine model of liver cirrhosis.
AB  - Liver fibrosis results from chronic damage to the liver by chronic hepatitis,
      alcohol, and toxic agents. A characteristic of liver fibrosis is an accumulation
      of extracellular matrix (ECM) protein, which distorts the hepatic architecture by
      forming a fibrous scar, and the subsequent development of regenerating nodules
      defines cirrhosis. Transforming growth factor (TGF)-beta1, one of the most
      powerful profibrogenic mediators, plays a major role in the development of liver
      cirrhosis and regulates ECM gene expression and matrix degradation. This study
      elucidates the changes of TGF-beta1-mediated signals during liver fibrogenesis by
      using RNA interference. In this experiment, the TGF-beta1 siRNAs reduced the
      expression of TGF-beta1 in the livers of CCl(4) injection compared with those of
      control group, and the expression of type I collagen and alpha-smooth muscle
      actin was decreased. In conclusion, this study demonstrates that TGF-beta1 siRNAs
      inhibit TGF-beta1 expression in the murine model of liver cirrhosis and might be
      a good therapeutic strategy to prevent liver cirrhosis in human.

PMID- 16579973
TI  - Cell-free translation system from Drosophila S2 cells that recapitulates RNAi.
AB  - RNA interference (RNAi) is a fundamental mechanism of gene regulation in a
      variety of organisms. In Drosophila cells, long double-stranded RNAs (dsRNAs) are
      processed into 21- to 23-nucleotide double-stranded fragments, termed short
      interfering RNAs (siRNAs). The siRNAs trigger sequence-specific mRNA degradation,
      which results in the inhibition of gene expression. These phenomena can be
      recapitulated in vitro in lysates of Drosophila syncytial blastoderm embryos. In
      the present work, we used the common Drosophila cell line, Schneider Line 2 (S2),
      as a source to establish a cell-free translation system. We demonstrate here that
      the S2 cell-free translation system can recapitulate RNAi. Both long dsRNAs and
      siRNAs can trigger RNAi in this system, and the silencing effects are
      significant. This system should provide an important tool for biochemical
      analyses of the RNAi mechanism.

PMID- 16579974
TI  - A complex of DNA gyrase and RNA polymerase fosters transcription in Mycobacterium
      smegmatis.
AB  - We report here the existence of a complex between RNA polymerase (RNAP) and DNA
      gyrase in Mycobacterium smegmatis. The interaction between the two enzymes was
      detected during our attempts to purify DNA gyrase from M. smegmatis. RNAP
      subunits co-eluted along with DNA gyrase in two different affinity chromatography
      column procedures employed to purify the latter enzyme. A complex containing both
      the enzymes was isolated through gel filtration chromatography and sucrose
      density gradient centrifugation of the cell free extracts. The complex exhibited
      both DNA supercoiling and transcription activities. Reduction in the
      transcription activity of the complex in the presence of DNA gyrase inhibitor
      indicates a role for DNA gyrase in stimulating transcription.

PMID- 16579975
TI  - Cellular FLICE-like inhibitory protein (c-FLIP): a novel target for Taxol-induced
      apoptosis.
AB  - It is known that by binding to the FAS-associated death domain (FADD) protein
      and/or caspases-8 and -10 at the level of the death-inducing signaling complex
      (DISC), cellular FLICE-like inhibitory protein (c-FLIP) can prevent apoptosis
      triggered by death-inducing ligands. We investigated whether the c-FLIP splice
      variants, c-FLIP long [c-FLIP(L)] and c-FLIP short [c-FLIP(S)], play a role in
      Taxol-induced apoptosis. Our results showed that low Taxol concentrations
      triggered caspase-8- and caspase-10-dependent apoptosis in the CCRF-HSB-2 human
      lymphoblastic leukemia cell line, and induced the down-regulation of c-FLIP(S)
      and c-FLIP(L). Taxol decreased the expression of c-FLIP by a post-transcriptional
      and caspase-independent mechanism. To explore the distinct functions of the c
      FLIP variants in Taxol-induced apoptosis, we transfected the cells with
      expression vectors carrying c-FLIP(L) and c-FLIP(S) in the sense orientation or c
      FLIP(S) in the antisense orientation [c-FLIP(S)-AS]. Caspases-8 and -10 were more
      efficiently activated in the c-FLIP(S)-AS strain treated with 5-50nM Taxol, which
      revealed that c-FLIP regulates Taxol-induced apoptosis by interacting with these
      caspases. Furthermore, our data showed that increased expression of c-FLIP(L) or
      c-FLIP(S) reduced apoptosis at 5-50nM Taxol concentrations suggesting that both
      isoforms of c-FLIP prevent Taxol-induced apoptosis. These results revealed that
      Taxol induces apoptosis by down-regulating c-FLIP(S) and c-FLIP(L) expression.

PMID- 16579976
TI  - Somato-dendritic distribution of 5-HT(1A) and 5-HT(1B) autoreceptors in the BDNF-
      and cAMP-differentiated RN46A serotoninergic raphe cell line.
AB  - The rapid differentiating effects of brain-derived neurotrophic factor (BDNF) or
      dibutyryl-cAMP (dBcAMP) were characterized on RN46A, a rat raphe-derived neuronal
      cell line. After BDNF treatment, RN46A cells were serotonin-immunopositive and
      bipolar, and expressed the microtubule-associated-protein 2 (Map2). After dBcAMP
      treatment, the cells often became multipolar, bearing very long processes
      strongly immunopositive for serotonin and Map2. Under both conditions, the
      expression and distribution of 5-HT(1A) and 5-HT(1B) autoreceptors remained
      identical. 5-HT(1A) and Map2 immunolabelings were superimposable, as expected of
      their somato-dendritic targeting. Surprisingly, the distribution of 5-HT(1B)
      immunoreactivity was similar, in contrast with its usual localization in axons
      and nerve terminals in the brain. In conclusion, both BDNF and cAMP
      differentiated RN46A cells towards a neuronal serotoninergic-like phenotype
      without the typical differential targeting of the 5-HT(1) autoreceptors, an
      interesting model to study the molecular mechanisms ensuing the targeting of 5
      HT(1) autoreceptors to somas and dendrites.

PMID- 16579978
TI  - Ethanol dilates coronary arteries and increases coronary flow via transient
      receptor potential vanilloid 1 and calcitonin gene-related peptide.
AB  - OBJECTIVES: Consumption of alcoholic beverages reduces the risk of coronary
      artery disease (CAD), and epidemiological studies have shown that ethanol per se
      is protective. However, the mechanism by which ethanol exerts protection is not
      fully known. Ethanol can stimulate neuropeptide-containing primary sensory
      neurons via the activation of transient receptor potential vanilloid 1 (TRPV1).
      Here, we have studied whether ethanol-mediated TRPV1 activation causes the
      release of calcitonin gene-related peptide (CGRP) that, via dilatation of
      coronary arteries and other mechanisms, may protect the heart from CAD. METHODS
      AND RESULTS: Ethanol caused a marked relaxation of small-sized porcine isolated
      coronary (0.008-2.37%, w/v) and human isolated gastro-epiploic (0.0008-2.37%,
      w/v) arteries in vitro, an effect that was abolished by capsaicin
      desensitization, the TRPV1 antagonist capsazepine, and the CGRP receptor
      antagonist, CGRP(8-37). In guinea-pig isolated and perfused hearts, ethanol
      (0.079-0.79%, w/v) increased baseline coronary flow in a concentration-dependent
      manner: 0.237% ethanol doubled baseline coronary flow. This effect was also
      abolished by capsaicin-desensitization, capsazepine, and CGRP((8-37)). Finally,
      the ethanol-induced increase in CGRP release from guinea-pig isolated and
      perfused hearts and from slices of porcine coronary arteries was abolished by
      capsaicin-desensitization and by capsazepine. Similar functional and
      neurochemical results were obtained in all preparations with capsaicin.
      CONCLUSIONS: Ethanol, at low concentrations not dissimilar from those found in
      blood following low to moderate consumption of alcoholic beverages, releases CGRP
      within coronary arteries via stimulation of TRPV1 on perivascular sensory nerve
      terminals. Ethanol-induced release of CGRP may contribute to the reduction in the
      risk of CAD associated with alcohol consumption by various mechanisms, including
      the increase in coronary flow and arterial dilatation.

PMID- 16579979
TI  - Anti-P- and E-selectin therapy prevents abortion in the CBA/J x DBA/2J
      combination by blocking the migration of Th1 lymphocytes into the foetal-maternal
      interface.
AB  - Leukocyte migration into inflamed tissues comprises dynamic interactions between
      immune and endothelial cells through events controlled by adhesion molecules,
      e.g., P- and E-selectins, which mediate Th1 cells recruitment after injury. Since
      miscarriage is known to be a Th1 event and selectins are expressed at the murine
      foetal-maternal interface, the purpose of our study was to investigate whether
      blocking P- and E-selectins before implantation could inhibit Th1 migration into
      the foetal-maternal interface and thus prevent foetal rejection. DBA/2J-mated
      CBA/J females were treated with monoclonal antibodies (mAbs) against P-selectin
      or with both, anti-P- and anti-E-selectins combined on days 2 and 4 of pregnancy.
      PBS-treated females served as controls. Our data revealed a significant
      improvement in pregnancy outcome in both treated groups compared to the control,
      which is due to the effectiveness of the mAb against P-selectin, since the
      treatment with anti-E-selectin alone could not prevent abortion. We further
      observed that there was diminished Th1 cytokine production by decidual immune
      cells in all treated groups in comparison to the controls. Our data first confirm
      the important role of P-selectin in mediating the extravasation of abortive
      cells, while opening new therapeutic opportunities.

PMID- 16579977
TI  - Strain background effects and genetic modifiers of hearing in mice.
AB  - Genetic modifiers can be detected in mice by looking for strain background
      differences in inheritance or phenotype of a mutation. They can be mapped by
      analyses of appropriate linkage crosses and congenic lines, and modifier genes of
      large effect can be identified by positional-candidate gene testing. Inbred
      strains of mice vary widely in onset and severity of age-related hearing loss
      (AHL), an important consideration when assessing hearing in mutant mice. At least
      8 mapped loci and a mitochondrial variant (mt-Tr) are known to contribute to AHL
      in mouse strains; one locus (ahl) has been identified as a variant of the
      cadherin 23 gene (Cdh23(753A/G)). This variant also was shown to modify hearing
      loss associated with the Atp2b2(dfw-2J) and Mass1(frings) mutations. The hearing
      modifier (Moth1) of tubby (Tub(tub)) mutant mice was shown to be a strain variant
      of the Mtap1a gene. Human hearing modifiers include DFNM1, which suppresses
      recessive deafness DFNB26, and a nuclear gene that modulates the severity of
      hearing loss associated with a mitochondrial mutation. Recently, a variant of the
      human ATP2B2 gene was shown to exacerbate hearing loss in individuals homozygous
      for a CDH23 mutation, similar to the Atp2b2(dfw-2J)-Cdh23(753A/G) interaction
      affecting hearing in mice. Because modifier genes and digenic inheritance are not
      always distinguishable, we also include in this review several examples of
      digenic inheritance of hearing loss that have been reported in both mice and
      humans.

PMID- 16579980
TI  - Historical milestones in measurement of HDL-cholesterol: impact on clinical and
      laboratory practice.
AB  - High-density lipoprotein cholesterol (HDL-C) comprises a family of particles with
      differing physicochemical characteristics. Continuing progress in improving HDL-C
      analysis has originated from two separate fields-one clinical, reflecting
      increased attention to HDL-C in estimating risk for coronary heart disease (CHD),
      and the other analytical, reflecting increased emphasis on finding more reliable
      and cost-effective HDL-C assays. Epidemiologic and prospective studies
      established the inverse association of HDL-C with CHD risk, a relationship that
      is consistent with protective mechanisms demonstrated in basic research and
      animal studies. Atheroprotective and less atheroprotective HDL subpopulations
      have been described. Guidelines on primary and secondary CHD prevention, which
      increased the workload in clinical laboratories, have led to a revolution in HDL
      C assay technology. Many analytical techniques including ultracentrifugation,
      electrophoresis, chromatography, and polyanion precipitation methods have been
      developed to separate and quantify HDL-C and HDL subclasses. More recently
      developed homogeneous assays enable direct measurement of HDL-C on an automated
      analyzer, without the need for manual pretreatment to separate non-HDL. Although
      homogeneous assays show improved accuracy and precision in normal serum,
      discrepant results exist in samples with atypical lipoprotein characteristics.
      Hypertriglyceridemia and monoclonal paraproteins are important interfering
      factors. A novel approach is nuclear magnetic resonance spectroscopy that allows
      rapid and reliable analysis of lipoprotein subclasses, which may improve the
      identification of individuals at increased CHD risk. Apolipoprotein A-I, the
      major protein of HDL, has been proposed as an alternative cardioprotective marker
      avoiding the analytical limitations of HDL-C.

PMID- 16579981
TI  - Klotho gene polymorphism may be a genetic risk factor for atherosclerotic
      coronary artery disease but not for vasospastic angina in Japanese.
AB  - BACKGROUND: The klotho gene, originally identified by insertional mutagenesis in
      mice, suppresses multiple aging phenotypes, including atherosclerosis. We tested
      the hypothesis that the G-395A polymorphism of the klotho gene is associated with
      increased risk for 2 types of ischemic heart disease in Japanese. METHODS: The
      study population consisted of 197 patients with coronary heart disease (CAD) who
      had >75% luminal diameter narrowing, 77 patients with vasospastic angina (VSA)
      without significant fixed coronary artery disease, and 331 healthy control
      subjects. RESULTS: The frequency of the A allele carriers of the klotho gene was
      significantly higher in the CAD group than in the control group (29.9% vs.
      19.0%). The unadjusted odds ratio for CAD in the A allele carriers compared with
      the control group was 1.82 (p=0.004) and a traditional risk-adjusted logistic
      regression model revealed that the A allele was an independent predictor of CAD
      (odds ratio, 1.76; p=0.03). In contrast, the frequency of the A allele carriers
      was not significantly different in the VSA group (23.4%; adjusted odds ratio,
      1.18. CONCLUSIONS: The -395A polymorphism of the human klotho gene may be a
      genetic risk factor for IHD and not for VSA.

PMID- 16579982
TI  - Oxidative response of rat lung tissue after crown ethers exposure and the effects
      of alpha-tocopherol treatment.
AB  - BACKGROUND: Ionophoric properties of crown ethers enable them ideally to
      transport across membranes and interfere with different living systems. We
      studied cytotoxicity effects of 18-crown-6 and 15-crown-5 and the role of
      oxidative stress in rat lung tissue culture. METHODS: We assayed the effects of
      these crown ethers in a range of doses (0.1 to 2 mmol/l) on lipids and proteins
      oxidative damages end products; malondialdehyde (MDA) and dityrosine and on the
      activity of antioxidant enzymes; superoxide dismutase (SOD), glutathione
      peroxidase (GPX), catalase (CAT), in rat lung tissue culture by spectrometry and
      HPLC. RESULTS: Both compounds significantly increased the levels of MDA,
      dityrosine and enzyme activities at doses >0.5 mmol/l after 48-h incubation in
      the lung tissue, representing promotion of ROS generation with respect to
      control. These effects were more considerable for 18-crown-6 than 15-crown-5.
      Treatment of lung tissue with 30 microm of alpha-tocopherol in addition to 2
      mmol/l of crown ethers showed significant decrease on the levels of enzyme
      activities, MDA and dityrosine. CONCLUSION: We showed the oxidative radicals
      forming ability of crown ethers as documented in their toxicity effects through
      lipid and proteins oxidation damages.

PMID- 16579983
TI  - Loss of Cited2 affects trophoblast formation and vascularization of the mouse
      placenta.
AB  - Cited2 is widely expressed in the developing embryo and in extraembryonic tissues
      including the placenta. Gene expression can be induced by a number of factors;
      most notably by the hypoxia inducible transcription factor, HIF1, under low
      oxygen conditions. Cited2 encodes for a transcriptional co-factor that in vitro
      can act as both a positive and negative regulator of transcription. This function
      is due to its interaction with CBP/p300 and appears to depend on whether Cited2
      enables CBP/p300 to interact with the basic transcriptional machinery, or if its
      binding prevents such an interaction from occurring. Here, we report a novel
      function for Cited2 in placenta formation, following gene deletion in mouse. In
      the absence of Cited2 the placenta and embryo are significantly small from 12.5
      and 14.5 dpc respectively, and death occurs in utero. Cited2 null placentas have
      fewer differentiated trophoblast cell types; specifically there is a reduction in
      trophoblast giant cells, spongiotrophoblasts and glycogen cells. In addition, the
      fetal vasculature of the placenta is disorganised and there are fewer
      anastomosing capillaries. Given that Cited2 is expressed in both trophoblasts and
      the fetal vasculature, the observed defects fit well with the sites of gene
      expression. We conclude that Cited2 is required for normal placental development
      and vascularisation, and hence for embryo viability.

PMID- 16579984
TI  - A new model of experimental subretinal neovascularization in the rabbit.
AB  - Existing animal models of choroidal neovascularization (CNV) present several
      problems: they are hard to reproduce, they are inefficient, and the CNV created
      is not sustainable. The purpose of this study is to develop a highly efficient,
      reliable, sustainable rabbit model of CNV to facilitate the study of anti
      angiogenic and anti-proliferative therapies for ocular diseases. Twenty-two
      pigmented rabbits were used in this study. Eleven rabbits received subretinal
      injections of either 10 microl of Matrigel with 500 ng of vascular endothelial
      growth factor (VEGF) or 20 microl of Matrigel with 750 ng of VEGF; eight rabbits
      received subretinal injections of either 10 or 20 microl of Matrigel only; three
      rabbits used as controls received subretinal injections of 20 microl phosphate
      buffered saline (PBS) alone. Fundus photography, fluorescein angiography, optical
      coherence tomography, and histologic examinations were performed 1, 2, 4, and 9
      weeks after injection. All experimental eyes showed angiographic leakage within
      this localized area 1 week after injection. The amount of leakage usually
      increased at weeks 2 and 4 and, in most cases, persisted at week 9. Control eyes
      demonstrated no leakage at any time point. Optical coherence tomography of
      treated eyes showed subretinal fluid and the presence of a lesion, possibly
      vascular or fibrotic, at the site of the leakage. Histologic analysis confirmed
      the presence of new subretinal blood vessels in the areas of Matrigel deposit. In
      conclusion, this novel method provides a highly reproducible, reliable, and
      sustainable rabbit model of experimental choroidal neovascularization. Such a
      model may prove useful for screening new anti-angiogenic therapies in a larger
      animal eye.

PMID- 16579985
TI  - Low frequency temporal modulation of light promotes a myopic shift in refractive
      compensation to all spectacle lenses.
AB  - Emmetropization, the process by which ocular growth of young animals adapts to
      ensure focussed retinal images, can be disrupted by high frequency flicker,
      causing a hypermetropic shift. Emmetropization can also be disrupted
      differentially, in a sign dependent manner, by pharmacological alteration of the
      balance of activation of the ON and OFF retinal sub-systems in normal light or by
      rearing in an environment with a moving spatiotemporally varied diamond pattern
      (yielding local sawtooth illumination on the retina). Thus the aim of this
      experiment was to determine whether low frequency temporal modulation alone was
      sufficient to cause defocus sign-dependent interference with compensation. Chicks
      were reared for 6 or 7 days with monocular +/-10 D, 0 D, or No Lenses in a 12h
      light/dark cycle. Luminance of the environment was temporally modulated during
      the light cycle with a non-square wave profile pulse of 250 msec duration, with
      the illumination fluctuating between 1.5 and 180 lux at 1 Hz, 2 Hz, 4 Hz or with
      no flicker (0 Hz-180 lux). Final refractive state and ocular dimensions, measured
      using retinoscopy and A-scan ultrasonography, demonstrated that in the absence of
      temporal luminance modulation (0 Hz), chicks compensated to induced defocus in
      the expected sign-dependent manner. However, under 1, 2 and 4 Hz flickering light
      conditions, there was an overall myopic offset of approximately 6D across lens
      groups with refractive compensation to positive lenses more strongly inhibited.
      This myopic offset was reflected by increases in the depth of both vitreous and
      anterior chambers. However, luminance modulation had no effect on refraction or
      ocular parameters in the No Lens conditions. This is a hitherto unreported strong
      interaction between lens wear and low frequency temporally modulated light, with
      the refractive compensation mechanism being overridden by a generalized myopic
      shift.

PMID- 16579986
TI  - Tyrosinase biosynthesis in adult mammalian retinal pigment epithelial cells.
AB  - Tyrosinase (EC 1.14.18.1) is the rate limiting enzyme of melanogenesis and it is
      unclear whether it is synthesized in postnatal retinal pigment epithelium (RPE).
      Cultured RPE cells from cattle were fed with isolated rod outer segments (ROS).
      After phagocytosis, RPE cells were tested for tyrosinase presence and activity
      with three independent methods: (1) ultrastructural DOPA (l-3,4
      dihydroxyphenylalanine) histochemistry (2) immunocytochemistry with anti
      tyrosinase antibodies (3) measuring tyrosine hydroxylase activity using
      [(3)H]tyrosine. With all three methods tyrosinase was found in RPE cells after
      ROS-feeding but was absent without feeding. In contrast to the classical
      hypothesis, we demonstrated with three independent methods that the expression of
      tyrosinase and its enzymatic activity are induced in cultured adult RPE by
      phagocytosis of rod outer segments (ROS) in vitro.

PMID- 16579987
TI  - Androgen regulation of lipogenic pathways in the mouse meibomian gland.
AB  - We hypothesize that androgens regulate lipogenesis in the meibomian gland. To
      test this hypothesis, we sought to determine whether androgens increase the mRNA
      levels of key lipogenic enzymes involved in the synthesis of cholesterol and
      fatty acids. In addition, we examined whether androgens stimulate the expression
      of genes for sterol regulatory element binding proteins (SREBP) 1 and 2, which
      are transcription factors that play an important role in the coordinate
      regulation of lipogenic enzymes. Meibomian glands were obtained from castrated
      mice, that were treated with vehicle or testosterone for 2 weeks. Tissues were
      processed for the analysis of selected mRNAs by real-time PCR. Our results show
      that testosterone increases the mRNA levels of critical lipogenic enzymes,
      including those related to ATP-citrate lyase, acetyl-CoA-synthase, acetyl-CoA
      carboxylase, acetoacetyl-CoA-synthase and 3-hydroxy-3-methylglutaryl CoA synthase
      1. Our findings also demonstrate that androgens upregulate the expression of
      genes encoding the transcription factors SREBPs 1 and 2. Our results indicate
      that androgens may control multiple aspects of lipogenesis in the meibomian
      gland.

PMID- 16579988
TI  - Heat shock protein 60 modified with O-linked N-acetylglucosamine is involved in
      pancreatic beta-cell death under hyperglycemic conditions.
AB  - The objective of this study was to identify proteins modified with O-linked N
      acetylglucosamine (O-GlcNAc) in pancreatic beta-cells and to understand their
      roles in cell death under hyperglycemic conditions. Here we report that heat
      shock protein 60 (HSP60) is modified with O-GlcNAc. Levels of O-GlcNAcylated
      HSP60 increased twofold in response to hyperglycemic conditions. HSP60 is a
      chaperonin known to bind to Bax in the cytoplasm under normoglycemic conditions.
      Under hyperglycemic conditions, Bax detached from O-GlcNAcylated HSP60 and
      translocated to mitochondria. Hyperglycemic conditions were also associated with
      cytochrome c release, caspase-3 activation, and cell death, suggesting that
      elevated O-GlcNAcylation of HSP60 interferes with HSP60-Bax interactions, leading
      to pancreatic beta-cell death.

PMID- 16579989
TI  - EKLF/KLF1 is ubiquitinated in vivo and its stability is regulated by activation
      domain sequences through the 26S proteasome.
AB  - Erythroid Kruppel-like factor (EKLF/KLF1) is an erythroid specific, C(2)H(2) zinc
      finger transcription factor that is essential for the proper chromatin structure
      and expression of the adult beta-globin gene. Herein, we determine that 26S
      proteasome inhibitors lead to an accumulation of EKLF protein in murine
      erythroleukemia (MEL) cells. In addition, EKLF half-life in both MEL cells (<3h)
      and fetal liver cells (between 6 and 9h) is stabilized in the presence of these
      inhibitors. EKLF is ubiquitinated in vivo, however its modification does not rely
      on a particular internal lysine. Finally, EKLF contains two PEST sequences within
      its N-terminus that have no effect on the ability of EKLF to be ubiquitinated but
      contribute to its destabilization.

PMID- 16579990
TI  - Growth factor receptors in helminth parasites: signalling and host-parasite
      relationships.
AB  - Parasitic helminths remain major pathogens of both humans and animals throughout
      the world. The success of helminth infections depends on the capacity of the
      parasite to counteract host immune responses but also to exploit host-derived
      signal molecules for its development. Recent progress has been made in the
      characterization of growth factor receptors of various nematode and flatworm
      parasites with the demonstration that transforming growth factor beta (TGF-beta),
      epidermal growth factor (EGF) and insulin receptor signalling pathways are
      conserved in helminth parasites and potentially implicated in the host-parasite
      molecular dialogue and parasite development.

PMID- 16579991
TI  - Soluble cytochrome c-554, CycA, is not essential for photosynthetic electron
      transfer in Chlorobium tepidum.
AB  - We constructed a mutant lacking soluble cytochrome c-554 (CycA) by disruption of
      the cycA gene in the green sulfur bacterium Chlorobium tepidum. The mutant grew
      phototrophically with a growth rate slower than that of the wild type, suggesting
      that CycA is not essential for photosynthetic electron transfer even though CycA
      is known to work as an electron donor to the reaction center. The re-reduction of
      photo-oxidized cytochrome c(z) by quinol oxidoreductase was inhibited almost
      completely by the addition of stigmatellin in the mutant cells. This result
      indicates that, in the mutant cells, the linear electron transfer can occur from
      the quinol oxidoreductase to cytochrome c(z), and to reaction center P840 with no
      participation of CycA.

PMID- 16579992
TI  - Improvement of hypertension and vascular dysfunction by hydroxyhydroquinone-free
      coffee in a genetic model of hypertension.
AB  - Chlorogenic acid, a polyphenol found in coffee, has antihypertensive actions, but
      epidemiologic data on the effects of coffee on blood pressure are controversial.
      Specific coffee components that inhibit the hypotensive effect of chlorogenic
      acid and the physiologic mechanisms underlying the effects of coffee without
      these components were investigated. One component, hydroxyhydroquinone (HHQ),
      inhibited the hypotensive effects of chlorogenic acid in spontaneously
      hypertensive rats (SHR). The attenuation of hypertension by HHQ-free coffee was
      associated with nitric oxide, the suppression of mRNA expression of NAD(P)H
      oxidase, and the improvement in endothelium-dependent vasodilation in the aorta.
      Thus, HHQ-free coffee might regulate vascular tone by improving the
      bioavailability of nitric oxide in SHR.

PMID- 16579993
TI  - Reversible inhibition of caspase-3 activity by iron(III): potential role in
      physiological control of apoptosis.
AB  - Desferoxamine is known to induce apoptosis in cancer cells, but the mechanisms
      are still not fully understood. We have shown that iron(III) is a potent caspase
      3 inhibitor, and the inhibition is reversible by the iron chelating agent
      desferoxamine. Also, protein disulfide isomerase (PDI) is capable of activating
      caspase-3 inhibited by iron(III), likely by formation of iron-sulfur complex
      through its active site thiols. Data presented here suggests that iron(III) could
      be a potential inhibitor of apoptosis in vivo, by caspase-3-dependent inhibition
      with a possibility of recovery through PDI overexpression.

PMID- 16579994
TI  - Determinants of differential doxorubicin sensitivity between SCLC and NSCLC.
AB  - Doxorubicin (DOX) transport activity of Ral-interacting protein (RLIP76) in non
      small cell lung cancer (NSCLC) is approximately twice that of in small cell lung
      cancer (SCLC). Since protein-kinase-C (PKC)alpha mediated phosphorylation of
      RLIP76 causes doubling of the specific activity of RLIP76, and NSCLC cells are
      known to have greater PKCalpha activity, we examined the contribution of PKC
      mediated phosphorylation of RLIP76 towards intrinsic DOX-resistance in human
      NSCLC. Expression of a deletion mutant RLIP76(delPKCalpha-sites) followed by
      depletion of the wild-type RLIP76 using a siRNA targeted at one of the deleted
      regions resulted in generation of cells expressing only the mutant protein, which
      could not be phosphorylated by PKCalpha. DOX-transport activity of the mutant
      RLIP76 purified from NSCLC and SCLC was similar and comparable to that of RLIP76
      purified from the wild-type SCLC. However, this activity was significantly lower
      than that of RLIP76 purified from the wild-type NSCLC. After siRNA mediated
      depletion of PKCalpha, DOX-transport activities of RLIP76 purified from SCLC and
      NSCLC were indistinguishable. Depletion of PKCalpha inhibited the growth of NSCLC
      more than SCLC cells (70+/-3% vs. 43+/-5%, respectively). PKCalpha-depletion
      lowered the IC(50) of NSCLC cell lines for DOX to the same level as that observed
      for SCLC. RLIP76(-/-) mouse embryonic fibroblasts (MEFs) were significantly more
      sensitive to DOX as compared with RLIP76(+/+) MEFs (IC(50) 25 vs. 125nM,
      respectively). However, PKCalpha-depletion did not affect DOX-cytotoxicity
      towards RLIP76(-/-) MEFs, as opposed to RLIP76(+/+) MEFs which were sensitized by
      2.2-fold. These results demonstrate that RLIP76 is a primary determinant of DOX
      resistance, and that PKCalpha mediated accumulation defect and DOX-resistance in
      NSCLC is primarily due to differential phosphorylation of RLIP76 in SCLC and
      NSCLC.

PMID- 16579995
TI  - Follicle-stimulating hormone isoforms are not useful as pretreatment predictors
      of outcome in in vitro fertilization: a pilot study.
AB  - The objective of this study was to determine the predictive value of FSH isoforms
      for the outcome of IVF treatment. Although this pilot study comprises only a
      small number of patients, we conclude that because no statistical differences
      could be found in the isoform-composition between poor and good responders, it is
      not likely that FSH isoforms predict treatment outcome after IVF.

PMID- 16579996
TI  - Administration of goserelin acetate after uterine artery embolization does not
      change the reduction rate and volume of uterine myomas.
AB  - OBJECTIVE: To determine if goserelin immediately after uterine artery
      embolization (UAE) affected myoma reduction. DESIGN: Randomized pilot study
      (level 1). SETTING: Teaching hospital. PATIENT(S): Twenty-six women.
      INTERVENTION(S): All patients underwent UAE, and then 12 patients received 10.8
      mg of goserelin 24 hours later. The treatment group was 5 years older: 43 versus
      37.7 years. Uterine and myoma volumes were measured by ultrasound 2 weeks before
      UAE and at 3, 6, and 12 months. MAIN OUTCOME MEASURE(S): Uterine and fibroid
      volumes. RESULT(S): Pretreatment uterine volume was 477 versus 556 cm3, and
      dominant fibroid volume was 257 versus 225 cm3 in the control versus goserelin
      groups. Analysis of variance measurements indicated that the change over time did
      not significantly differ between the two groups. By 12 months, the control group
      had a mean uterine volume reduction of 58%, while the goserelin group had a
      reduction of 45%. Dominant fibroid changes over time did not differ between the
      two groups. At 12 months, the mean fibroid volume had decreased by 86% and 58% in
      the control and goserelin groups, respectively. CONCLUSION(S): The addition of
      goserelin therapy to UAE did not alter the reduction rate or volume of uterine
      myomas.

PMID- 16579997
TI  - Two weeks of metformin improves clomiphene citrate-induced ovulation and
      metabolic profiles in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To determine if short courses of metformin (MET) administration in
      patients with polycystic ovary syndrome (PCOS) would reduce fasting insulin and
      improve the efficacy of clomiphene citrate (CC) to induce ovulation. DESIGN: A
      randomized prospective trial involving 31 subjects with PCOS and infertility.
      SETTING: University-based medical center. PATIENT(S): Obese patients (body mass
      index > 29 kg/m2) with PCOS. INTERVENTION(S): Patients with PCOS were treated
      either with CC or CC+MET for 2 weeks. MAIN OUTCOME MEASURE(S): Ovulation as
      determined by serum P, serum insulin, and total and free T. RESULT(S): In the
      CC/MET group, a significant increase in sex hormone-binding globulin (SHBG)
      levels, a decrease in fasting insulin, and an increase in fasting glucose/fasting
      insulin was detected on day 21 of the cycle. Of these parameters, only SHBG
      levels increased significantly in the CC group. In the CC/MET group, a
      significant increase in day 21 progesterone occurred, with 44% of subjects
      ovulating in the CC+MET group as compared with 6.7% in the CC group. Five
      subjects in the CC+MET group and none in the CC group conceived. Total and free
      testosterone levels did not change significantly for either group. CONCLUSION(S):
      In obese PCOS patients, 2 weeks of MET significantly reduces serum insulin and
      insulin resistance and increases SHBG levels, resulting in an improved response
      to CC. This regimen may be beneficial in noncompliant patients or those with
      intolerance to the side effects of MET.

PMID- 16579998
TI  - Serum soluble leptin receptor levels and free leptin index in women with
      polycystic ovary syndrome: relationship to insulin resistance and androgens.
AB  - OBJECTIVE: To evaluate levels of soluble receptor (sOB-R) and free leptin in
      women with polycystic ovarian syndrome (PCOS) and note any relationships with
      insulin resistance, adiposity, and androgens. Leptin is an adipokine that
      circulates in a free form and bound to an sOB-R. Only free leptin is biologically
      active. DESIGN: Prospective, case-control study. SETTING: University-based
      reproductive endocrinology practice. PATIENT(S): Forty women with PCOS and severe
      insulin resistance and 15 body mass index (BMI)-matched ovulatory controls.
      INTERVENTION(S): Measurements of serum insulin, leptin, sOB-R at fasting and
      during a standard oral glucose tolerance test (OGTT), and measurements before and
      after treatment with rosiglitazone. MAIN OUTCOME MEASURE(S): Fasting glucose,
      insulin, leptin, sOB-R, T, and DHEAS levels in women with PCOS and controls were
      measured to investigate the relationship of sOB-R and the free leptin index (FLI)
      to insulin, adipocity, and androgens and to investigate the effect of acute
      hyperinsulinemia during OGTT and the effect of improvement of insulin resistance
      with rosiglitazone on the leptin system. FLI was calculated by dividing leptin
      levels by sOB-R. RESULT(S): Total leptin and FLI correlated significantly with
      BMI in both patients with PCOS and in controls. There was a significant negative
      correlation between DHEAS and sOB-R in PCOS. Leptin, sOB-R, and FLI were not
      significantly different in the two groups, and neither sOB-R nor FLI correlated
      with insulin or glucose levels. The sOB-R levels increased significantly 3 hours
      after oral glucose ingestion, resulting in a significant decline in FLI.
      CONCLUSION(S): [1] Adiposity rather than insulin resistance appears to be the
      main determinant of leptin levels and FLI. [2] Acute increase in insulin levels
      during OGTT is associated with an increase in levels of sOB-R. [3] DHEAS may play
      a role in leptin bioavailability by modulating sOB-R levels.

PMID- 16579999
TI  - Sildenafil improves sexual functioning in premenopausal women with type 1
      diabetes who are affected by sexual arousal disorder: a double-blind, crossover,
      placebo-controlled pilot study.
AB  - OBJECTIVE: To verify whether sildenafil is effective in type 1 premenopausal
      women affected by sexual arousal disorder (SAD). DESIGN: Double-blind, crossover,
      placebo-controlled study. SETTING: Gynecological diabetic outpatient clinic and
      sexual clinic. PATIENT(S): Thirty-six type 1 premenopausal diabetic women
      affected by SAD. INTERVENTION(S): Two 8-week periods of sildenafil 100 mg,
      washout, and placebo, by two possible sequences. MAIN OUTCOMES MEASURE(S): Each
      woman submitted blood samples to measure HbA(1c), and T, free T (FT), and PRL.
      Efficacy was assessed [1] subjectively by the Personal Experiences Questionnaire
      based on the 5-point Likert scale, quantifying arousal, desire, orgasm, enjoyment
      of sexual activities, and frequency of sexual relationships; and [2] objectively
      by translabial color Doppler ultrasound to measure the resistance index (RI),
      pulsatility index (PI), peak systolic velocity (PSV), and end diastolic velocity
      of clitoral arteries. RESULT(S): Thirty-two women completed the study. The mean
      HbA(1c) value was 8.0% +/- 1.8%, and plasma concentrations of T, FT, and PRL were
      normal. Sildenafil seems to improve arousal, orgasm and sexual enjoyment, and
      dyspareunia in women affected by type 1 diabetes. However, by flowmetric
      measurements, the mean RI was significantly lower and both the mean PI and PSV of
      the clitoral arteries were significantly higher compared with baseline and
      placebo. CONCLUSION(S): Sildenafil seems to improve subjective sexual aspects and
      can be used to treat objectively genital arousal disorder of premenopausal women
      with type 1 diabetes.

PMID- 16580000
TI  - Accuracy of an optical active-marker system to track the relative motion of rigid
      bodies.
AB  - The measurement of relative motion between two moving bones is commonly
      accomplished for in vitro studies by attaching to each bone a series of either
      passive or active markers in a fixed orientation to create a rigid body (RB).
      This work determined the accuracy of motion between two RBs using an Optotrak
      optical motion capture system with active infrared LEDs. The stationary noise in
      the system was quantified by recording the apparent change in position with the
      RBs stationary and found to be 0.04 degrees and 0.03 mm. Incremental 10 degrees
      rotations and 10-mm translations were made using a more precise tool than the
      Optotrak. Increasing camera distance decreased the precision or increased the
      range of values observed for a set motion and increased the error in rotation or
      bias between the measured and actual rotation. The relative positions of the RBs
      with respect to the camera-viewing plane had a minimal effect on the kinematics
      and, therefore, for a given distance in the volume less than or close to the
      precalibrated camera distance, any motion was similarly reliable. For a typical
      operating set-up, a 10 degrees rotation showed a bias of 0.05 degrees and a 95%
      repeatability limit of 0.67 degrees. A 10-mm translation showed a bias of 0.03 mm
      and a 95% repeatability limit of 0.29 mm. To achieve a high level of accuracy it
      is important to keep the distance between the cameras and the markers near the
      distance the cameras are focused to during calibration.

PMID- 16580002
TI  - Methodology and sensitivity studies for finite element modeling of the inferior
      glenohumeral ligament complex.
AB  - The objectives of this research were to develop a methodology for three
      dimensional finite element (FE) modeling of the inferior glenohumeral ligament
      complex (IGHL complex) as a continuous structure, to determine optimal mesh
      density for FE simulations, to examine strains and forces in the IGHL complex in
      clinically relevant joint positions, and to perform sensitivity studies to assess
      the effects of assumed material properties. A simple translation test in the
      anterior direction was performed on a cadaveric shoulder, with the humerus
      oriented at 60 degrees of glenohumeral abduction and 0 degrees of
      flexion/extension, at 0 degrees , 30 degrees and 60 degrees of humeral external
      rotation. The geometries of the relevant structures were extracted from
      volumetric CT data to create a FE model. Experimentally measured kinematics were
      applied to the FE model to simulate the simple translation test. First principal
      strains, insertion site forces and contact forces were analyzed. At maximum
      anterior humeral translation, strains in the IGHL complex were highly
      inhomogeneous for all external rotation angles. The motion of the humerus with
      respect to the glenoid during the simple translation test produced a tangential
      load at the proximal and distal edges of the IGHL complex. This loading was
      primarily in the plane of the inferior glenohumeral ligament complex, producing
      an in-plane shear-loading pattern. There was a significant increase in strain
      with increasing angle of external rotation. The largest insertion site forces
      occurred at the axillary pouch insertion to the humerus (36.7N at 60 degrees of
      external rotation) and the highest contact forces were between the anterior band
      of the IGHL complex and the humeral cartilage (7.3N at 60 degrees of external
      rotation). Strain predictions were highly sensitive to changes in the ratio of
      bulk to shear modulus of the IGHL complex, while predictions were moderately
      sensitive to changes in elastic modulus of the IGHL complex. Changes to the
      material properties of the humeral cartilage had little effect on predicted
      strains. The methodologies developed in this research and the results of the mesh
      convergence and sensitivity studies provide a basis for the subject-specific
      modeling of the mechanics of the IGHL complex.

PMID- 16580003
TI  - Application of headspace solid phase microextraction to qualitative and
      quantitative analysis of tobacco additives in cigarettes.
AB  - Cigarettes may contain up to 10% by weight additives which are intended to make
      them more attractive. A fast and rugged method for a cigarette-screening for
      additives with medium volatility was developed using automatic headspace solid
      phase microextraction (HS-SPME) with a 65 microm carbowax-divinylbenzene fiber
      and gas chromatography-mass spectrometry (GC-MS) with standard electron impact
      ionisation. In three runs, each cigarette sample was extracted in closed
      headspace vials using basic, acidic and neutral medium containing 0.5 g NaCl or
      Na2SO4. Furthermore, the method was optimized for quantitative determination of
      17 frequently occurring additives. The practical applicability of the method was
      demonstrated for cigarettes from 32 brands.

PMID- 16580004
TI  - Effect of beta-lactoglobulin hydrolysis with thermolysin under denaturing
      temperatures on the release of bioactive peptides.
AB  - In this study, bovine beta-lactoglobulin A (beta-Lg A) was hydrolysed with
      thermolysin under non-denaturing and heat-denaturing conditions. The peptides
      released during hydrolysis were identified by HPLC-MS/MS. A total of 25 peptides
      were identified in the hydrolysate obtained at 37 degrees C for 5 min. Some of
      these peptides survived to further proteolysis even at higher incubation
      temperatures. Furthermore, novel cleavage sites localised in the most buried
      zones of beta-Lg and available for thermolysin were recognised when the
      incubation temperature increased in the range between 60 and 80 degrees C. Three
      new peptides, LDA, LKPTPEGD, and LQKW, appeared after 30 min hydrolysis at these
      incubation temperatures, but they were not identified in the 30-min hydrolysates
      obtained at 37 and 50 degrees C. Of special interest was the peptide LQKW,
      corresponding to the fragment f(58-61) that had been previously described as a
      potent angiotensin-converting enzyme-inhibitor (IC50 value of 34.7 microM).

PMID- 16580005
TI  - Application of a static solid-phase microextraction procedure combined with
      liquid-liquid extraction to determine poly(dimethyl)siloxane-water partition
      coefficients for selected polychlorinated biphenyls.
AB  - A static solid-phase microextraction (SPME) procedure combined with liquid-liquid
      extraction (LLE) was used to determine the poly(dimethyl)siloxane (PDMS)-water
      partition coefficients (K(f)) for selected polychlorinated biphenyl congeners
      (PCBs), including PCB 1, 15, 28, 47, 101, 153, 180, 202, 206, and 209. The
      accuracy for the measurements of analyte concentrations in the aqueous phase was
      ensured with a one-to-one recovery correction strategy employing one 13C-labeled
      PCB congener as a surrogate standard for each unlabeled PCB counterpart. The
      effects of coating thickness (7, 30, and 100 microm) and sample volume (130 mL
      and 2 L) on the K(f) values were examined experimentally and confirmed with
      paired t-tests. Significant dependence of K(f) values on coating thickness was
      found for a few heavily chlorinated congeners only, and was tentatively
      attributed to the use of the inaccurate effective coating volumes and the
      structural variation with these PDMS coatings. In addition, no significant
      differences in the log K(f) values of all analytes except for PCB 206 were found
      between the sample sizes of 130 mL and 2 L for both the 7- and 100-microm
      coatings. Overall, K(f) values obtained with 2-L sample containers were
      consistently higher than those reported in the literature, which is attributable
      to the selection of appropriate equilibrium times for SPME and direct
      measurements of aqueous analyte concentrations with LLE in the present study.

PMID- 16580006
TI  - Chromatographic analysis of dopamine metabolism in a Parkinsonian model.
AB  - The present study examined the metabolism of released dopamine from rat striatum
      upon chronic rotenone exposure. The sample separation was carried out by two
      dimensional, reversed-phase and ion pair reversed-phase chromatography using on
      line solid phase extraction enrichment. Reduced dopamine content and decreased
      extracellular level of [(3)H] and endogenous dopamine evoked by electrical
      stimulation indicated the injury of dopaminergic pathway. Sensitivity of
      dopaminergic neurons were increased to oxidative stress with enhanced release of
      dopamine and formation of oxidized metabolite dopamine quinone (DAQ). Utilizing
      multidimensional detection, EC at -100 mV reduction potential, the method has
      been applied for identification of DAQ and aminochrome (DAC).

PMID- 16580007
TI  - Nano-titanium dioxide composites for the enrichment of phosphopeptides.
AB  - Protein phosphorylation is one of the most important known posttranslational
      modifications and the strategy to enrich phosphopeptides becomes a critical issue
      for mapping protein phosphorylation sites. In this study, nano-titanium dioxide
      (TiO2) composites were synthesized, characterized, and demonstrated to have high
      loading capacity and high capture efficiency for enriching phosphopeptides. TiO2
      nanoparticles were first silanized with methacryloxypropyltrimethoxysilane
      (MPTMS) and then were photopolymerized in the presence of a diacrylate
      crosslinker. The chemical bonds formed by the reaction were confirmed by both FT
      IR and X-ray photoelectron spectroscopy (XPS). Scanning electron microscopy (SEM)
      further reveals that agglomeration of the particles was created by the
      crosslinking, which allowed the nanocomposites to be well retained within the
      cartridge and used as the chromatographic packing material. Titration with phenyl
      phosphate indicated that the TiO2 nanocomposites have two times as much phosphate
      binding capacity compared with 5 microm TiO2 particles. Moreover, based on
      repetitive analyses of the tryptic digest deduced from pure proteins as well as
      from protein mixtures containing phospho and non-phospho proteins, the capture
      efficiency of TiO2 nanocomposites was determined to be two to five times larger
      compared with 5 microm TiO2 particles. The cost for preparing nanocomposite TiO2
      is low and it holds great promises to be used as chromatographic materials for
      phosphopeptide enrichment.

PMID- 16580008
TI  - Role of microenvironment in the mixed Langmuir-Blodgett films.
AB  - This paper reports the pi-A isotherms and spectroscopic characteristics of mixed
      Langmuir and Langmuir-Blodgett (LB) films of nonamphiphilic carbazole (CA)
      molecules mixed with polymethyl methacrylate (PMMA) and stearic acid (SA). pi-A
      isotherm studies of mixed monolayer as well as the remarkable change in collapse
      pressure of the mixed monolayer isotherms definitely show that CA is incorporated
      into PMMA and SA matrices. However, CA is stacked in the PMMA/SA chains and forms
      microcrystalline aggregates, as is evidenced from the scanning electron
      micrograph picture. The nature of these aggregated species in the mixed LB films
      has been revealed by UV-vis absorption and fluorescence spectroscopic studies.
      The presence of two different kinds of band systems in the fluorescence spectra
      of the mixed LB films have been observed. This may be due to the formation of low
      dimensional aggregates in the mixed LB films. Intensity distribution of different
      band systems is highly sensitive to the microenvironment of two different
      matrices as well as also on the film thickness.

PMID- 16580009
TI  - Preparation and characterization of carbonyl iron/poly(butylcyanoacrylate)
      core/shell nanoparticles.
AB  - In this article a method is described to prepare composite colloidal
      nanoparticles, consisting of a magnetic core (carbonyl iron) and a biodegradable
      polymeric shell [poly(butylcyanoacrylate) or PBCA]. The method is based on the so
      called anionic polymerization procedure, often used in the synthesis of
      poly(alkylcyanoacrylate) nanospheres designed for drug delivery. Interest of this
      investigation is based upon the fact that the heterogeneous structure of the
      particles can confer them both the possibility to respond to external magnetic
      fields and to be used as drug carriers. In order to investigate to what extent do
      the particles participate of this mixed properties, we compare in this work the
      physical characteristics (structure, chemical composition, specific surface area
      and surface electrical and thermodynamic properties) of the core/shell particles
      with those of both the nucleus and the coating material. This preliminary study
      shows that the mixed particles display an intermediate behavior between that of
      carbonyl iron and PBCA spheres. Electrophoretic mobility measurements as a
      function of pH and as a function of KNO3 concentration, show a great similarity
      between the core/shell and pure polymer nanoparticles. Similarly, a surface
      thermodynamic study performed on the three types of particles demonstrated that
      the electron-donor component of the surface free energy of the solids is very
      sensitive to the surface composition. In fact, a measurable decrease of such
      component is found for core/shell particles as compared to carbonyl iron. We also
      analyzed the influence of the relative amounts of polymer and carbonyl iron on
      the characteristics of the composite particles: data on the coating thickness,
      the amount of polymer bound to the magnetic nuclei, the redispersibility
      characteristics of the suspensions and the surface electrical and thermodynamic
      properties, suggest that the optimal synthesis conditions are obtained for a 4/3
      initial monomer/carbonyl iron weight ratio.

PMID- 16580010
TI  - The effect of surface hydrophilicity on the behavior of embryonic cortical
      neurons.
AB  - The aim of this study was to investigate the interaction of mouse embryonic
      cortical neurons on P(L)LA and PLGA substrates, which were partially hydrolysed
      using potassium hydroxide (KOH). The chemical and topographical properties of the
      surfaces were characterized, and it was discovered that there was a decrease in
      the hydrophilicity for the P(L)LA with increasing concentration of KOH. This was
      due to chemical modifications to the surfaces of the substrates. Alternatively
      for the PLGA substrate, only the 0.1 M KOH treated sample had a significantly
      different hydrophilicity highlighting that surface erosion resulted at higher
      concentrations. The morphology of the neurons grown on the two substrates were
      compared to poly(D)lysine (positive control). The neurons formed colonies on all
      of the substrates, but were dramatically reduced in size in the case of the 0.1 M
      KOH treated substrates. This finding was attributed to the increases in cell
      spreading and the size of the cells, as they were larger, more elongated and
      bipolar like those on the positive control. However, there was a significant
      decrease in the total number of live cells per unit area. Therefore, on these
      materials when there was increased cellular spreading there was significantly
      higher cell death. Furthermore, unlike the 0, 0.2, and 0.4 M KOH treated
      substrates, there was an absence of large bundles of axons that extended between
      colonies on the 0.1 M sample, instead exhibiting short axons that grew in free
      space.

PMID- 16580011
TI  - Thermodiffusional transport of electrolytes in compact clays.
AB  - The macroscopic Soret coefficient S(T) was measured for three porous media,
      namely mica, glass powder, and natural compact clay. At a mean temperature of T =
      25 degrees C and with NaCl, S(T) for mica and glass powder was found to be equal
      to (3.1+/-0.7) x 10(-3) K(-1) and close to values for a free medium in agreement
      with theoretical predictions which are obtained under the assumption that the
      pressure gradient and the electric field are negligible on the pore scale. The
      main result is that for clay S(T) was found five times larger, presumably because
      of extra couplings with electrical phenomena. This latter measurement was
      confirmed by an independent technique based on the membrane potential.

PMID- 16580012
TI  - Sequential analysis of multiple analytes using a surface plasmon resonance (SPR)
      biosensor.
AB  - A sequential analysis method for the analysis of two analytes was developed using
      a surface plasmon resonance (SPR) biosensor. A sample with both analytes was
      introduced into the single sensing region and then each analyte was analyzed
      sequentially. Two detection models were devised for the samples with the
      following composition: (1) one target analyte resulting in a sensor response
      without any label and the other analyte with only additional label, (2) both
      target analytes requiring additional labels for detection. A standard curve for
      each model was prepared and applied for sequential analysis of anti-bovine serum
      albumin (anti-BSA) antibodies and horseradish peroxidase (HRP). The errors of the
      sequential analysis of Models 1 and 2 were found to be less than 6%, and this
      method was therefore acceptable for application. No cross-reaction arising from
      non-specific binding among the participating antigens and antibodies was shown to
      occur in Models 1 and 2. For optimization of the analyte binding capacity of
      immunoaffinity (IA), the concentration ratio of the molecular recognition element
      at the immobilization step was adjusted. Subsequently, from the measurement of
      the maximum sensor response (R(max)), optimization of the analyte binding
      capacity could be made. Using Model 2, the feasibility of sequential analysis was
      demonstrated by detecting levels of human chorionic gonadotropin (hCG) and human
      albumin (hA) in healthy human urine, since both proteins are known to be related
      to abortion and preterm delivery during early pregnancy.

PMID- 16580013
TI  - Salivation pattern of Rhodnius prolixus (Reduviidae; Triatominae) in mouse skin.
AB  - The objective of this work was to study the pattern of salivation of triatomines
      during feeding in mouse skin. Rhodnius prolixus was fed with a solution of the
      dye acridine orange or fluorescein. The saliva was efficiently labelled with
      acridine orange, probably due to the difference in pH between the salivary gland
      (6.0) and the hemolymph (6.5-7.0). This procedure was not effective at labelling
      the saliva of Triatoma infestans, however, fluorescent labelling of R. prolixus
      saliva allowed us to demonstrate that salivation occurs during entire feeding
      process. The saliva is released soon after the bite. In the probing phase, saliva
      is pumped continuously in the host skin, including around the blood vessels.
      During the engorgement phase, saliva is observed in a bolus within the blood
      vessel and some of it is sucked up by the insect, together with blood. The
      frequency of saliva emission inside the vessels was low (0.51+/-0.18 Hz). The
      saliva deposition in the microcirculation is continuous and modulated by the
      frequency of the cibarial pump because, when functioning at high frequency,
      cibarial pump sucks almost all saliva to the insect gut. This mechanism would
      determine the quantity of saliva deposited in the microcirculation as necessary,
      and consequently minimizing the host's immune response to salivary antigens.

PMID- 16580014
TI  - Differential gene expression in Perillus bioculatus nymphs fed a suboptimal
      artificial diet.
AB  - Fragments of two artificial diet up-regulated and two prey up-regulated
      transcripts were isolated from the predatory Pentatomid Perillus bioculatus using
      suppression subtractive hybridization. A BlastX search found similarities for two
      diet-upregulated clones, i.e., the tyrosine-3-monooxygenase gene and the gene for
      the chitin binding protein, Gasp. The probe generated from the tyrosine-3
      monooxygenase clone hybridized to two transcripts 2.3 and 1.2kb in size. The two
      transcripts were differentially regulated: the 2.3kb transcript was upregulated
      in the first and late third instar diet-fed nymphs, whereas the 1.2kb transcript
      was upregulated in the second and early third instar diet-fed nymphs. The Gasp
      gene was upregulated in late third instar nymphs. A positive correlation was
      found between levels of expression of the isolated genes and the number of
      generations the insects had been reared on the artificial diet.

PMID- 16580015
TI  - Ecdysteroid titers and developmental expression of ecdysteroid-regulated genes
      during metamorphosis of the yellow fever mosquito, Aedes aegypti (Diptera:
      Culicidae).
AB  - Ecdysteroid titers and expression profiles of ecdysone-regulated genes were
      determined during the last instar larval and during the pupal stages of Aedes
      aegypti (Diptera: Culicidae). Three peaks of ecdysteroids occurring at
      approximately 24, 30-33 and 45-48h after ecdysis to the fourth instar larval
      stage were detected. In the pupa, a large peak of ecdysteroids occurred between 6
      and 12h after ecdysis to the pupal stage. A small rise in ecdysteroids was also
      detected at the end of the pupal stage. Quantitative reverse transcriptase
      polymerase chain reaction analyses of the expression of ecdysone receptors and
      ecdysone-regulated genes showed that the peaks of expression of most of these
      genes coincided with the rise in ecdysteroid levels during the last larval and
      pupal stages. In the last larval stage, ecdysteroid titers and mRNA expression
      profiles of ecdysone-regulated genes are similar to those observed for Drosophila
      melanogaster. However, in the early pupal stage, both ecdysteroid titers and the
      expression of ecdysone-regulated genes are somewhat different from those observed
      in D. melanogaster, probably because the duration of the pupal stage in D.
      melanogaster is 84h while in Ae. aeqypti the duration is only 48h. These data
      which describe the relationship between ecdysteroid titers and mRNA levels of Ae.
      aegypti ecdysteroid-regulated genes lay a solid foundation for future studies on
      the hormonal regulation of development in mosquitoes.

PMID- 16580016
TI  - First record of Clonostachys rosea (Ascomycota: Hypocreales) as an
      entomopathogenic fungus of Oncometopia tucumana and Sonesimia grossa (Hemiptera:
      Cicadellidae) in Argentina.
AB  - Clonostachys rosea (Link: Fries) Schroers, Samuels, Seifert, and Gams
      (Ascomycota: Hypocreales) has been reported as a mycoparasite of fungi and
      nematodes and as saprobe in soils, but this fungus has not been reported
      previously to be entomopathogenic. Many species of cicadellid leafhoppers cause
      economic damage to crops as vectors of plant pathogens. In the present work, we
      report the first record of C. rosea as an entomopathogenic fungus of two
      leafhoppers pest, Oncometopia tucumana and Sonesimia grossa (Hemiptera:
      Cicadellidae), in Argentina and evaluate the pathogenicity of C. rosea against
      them.

PMID- 16580017
TI  - The efficacy of two entomopathogenic biocontrol agents against adult Thrips palmi
      (Thysanoptera:Thripidae).
AB  - The efficacy of the two entomopathogenic biocontrol agents, Steinernema feltiae
      (Filipjev) and Lecanicillium muscarium (Petch), against juvenile Thrips palmi
      Karny in the laboratory situation is well documented. This study investigated the
      extrapolation of this knowledge to the control of adult stages. S. feltiae caused
      significantly higher mortality to juvenile T. palmi than to adult stages, whereas
      L. muscarium had a more significant impact on adult stages. The potential to
      develop an IPM strategy to control T. palmi utilising the two entomopathogens is
      discussed.

PMID- 16580018
TI  - Structure of the Sulfolobus solfataricus alpha-glucosidase: implications for
      domain conservation and substrate recognition in GH31.
AB  - The crystal structure of alpha-glucosidase MalA from Sulfolobus solfataricus has
      been determined at 2.5Angstrom resolution. It provides a structural model for
      enzymes representing the major specificity in glycoside hydrolase family 31
      (GH31), including alpha-glucosidases from higher organisms, involved in glycogen
      degradation and glycoprotein processing. The structure of MalA shows clear
      differences from the only other structure known from GH31, alpha-xylosidase YicI.
      MalA and YicI share only 23% sequence identity. Although the two enzymes display
      a similar domain structure and both form hexamers, their structures differ
      significantly in quaternary organization: MalA is a dimer of trimers, YicI a
      trimer of dimers. MalA and YicI also differ in their substrate specificities, as
      shown by kinetic measurements on model chromogenic substrates. In addition, MalA
      has a clear preference for maltose (Glc-alpha1,4-Glc), whereas YicI prefers
      isoprimeverose (Xyl-alpha1,6-Glc). The structural origin of this difference
      occurs in the -1 subsite where MalA residues Asp251 and Trp284 could interact
      with OH6 of the substrate. The structure of MalA in complex with beta-octyl
      glucopyranoside has been determined. It reveals Arg400, Asp87, Trp284, Met321 and
      Phe327 as invariant residues forming the +1 subsite in the GH31 alpha
      glucosidases. Structural comparisons with other GH families suggest that the GH31
      enzymes belong to clan GH-D.

PMID- 16580019
TI  - Standard conformations of beta-arches in beta-solenoid proteins.
AB  - Strand-turn-strand motifs found in beta-helical (more generally, beta-solenoid)
      proteins differ fundamentally from those found in globular proteins. The latter
      are primarily beta-hairpins in which the two strands form an antiparallel beta
      sheet. In the former, the two strands are relatively rotated by approximately 90
      degrees around the strand axes so that they interact via the side-chains, not via
      the polypeptide backbones. We call the latter structures, beta-arches, and their
      turns, beta-arcs. In beta-solenoid proteins, beta-arches stack in-register to
      form beta-arcades in which parallel beta-sheets are assembled from corresponding
      strands in successive layers. The number of beta-solenoids whose three
      dimensional structures have been determined is now large enough to support a
      detailed analysis and classification of beta-arc conformations. Here, we present
      a systematic account of beta-arcs distinguished by the number of residues, their
      conformations, and their propensity to stack into arcades with other like or
      unlike arches. The trends to emerge from this analysis have implications for
      sequence-based detection and structural prediction of other beta-solenoid
      proteins as well as for identification of amyloidogenic sequences and elucidation
      of amyloid fibril structures.

PMID- 16580020
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy: two novel mutations in the NOTCH3 gene in Chinese.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is a hereditary disorder caused by NOTCH3
      mutations, usually localized to exons 3 and 4, and characterized by recurrent
      subcortical infarctions, dementia and leukoencephalopathy. So far, there has been
      only limited information about CADASIL in Chinese population. OBJECTIVES: To
      analyze the NOTCH3 mutations in ethnic Chinese in Taiwan with clinically
      suspected CADASIL and to characterize their clinical and molecular features.
      METHODS: Mutation analysis of NOTCH3 by direct nucleotide sequencing was
      performed in eight unrelated Chinese patients with clinically suspected CADASIL.
      Skin biopsy with ultrastructural studies by electronic microscopy was performed
      in four patients. RESULTS: Five NOTCH3 mutations, S118C, R141C, R332C, R544C and
      C977S, respectively, were identified from five patients, of which S118C and C977S
      are novel. None of these nucleotide sequence variations could be found among 50
      healthy controls. Among the five mutations, two were in exon 4, and the other
      three were in exons 6, 11 and 18, respectively. Skin biopsy showed the presence
      of characteristic granular osmiophilic material only in the patient with the
      NOTCH3 mutation of R332C. CONCLUSION: Our study demonstrated the clinical and
      molecular features of CADASIL in Chinese patients and broadened the spectrum of
      NOTCH3 mutations. Lack of evidence of a strong clustering of mutations in a
      particular exon tentatively suggests that a comprehensive screening of NOTCH3
      mutation is still necessary for molecular diagnosis of CADASIL in Chinese
      population.

PMID- 16580021
TI  - A finite element simulation scheme for biological muscular hydrostats.
AB  - An explicit finite element scheme is developed for biological muscular hydrostats
      such as squid tentacles, octopus arms and elephant trunks. The scheme is
      implemented by embedding muscle fibers in finite elements. In any given element,
      the fiber orientation can be assigned arbitrarily and multiple muscle directions
      can be simulated. The mechanical stress in each muscle fiber is the sum of active
      and passive parts. The active stress is taken to be a function of activation
      state, muscle fiber shortening velocity and fiber strain; while the passive
      stress depends only on the strain. This scheme is tested by simulating extension
      of a squid tentacle during prey capture; our numerical predictions are in close
      correspondence with existing experimental results. It is shown that the present
      finite element scheme can successfully simulate more complex behaviors such as
      torsion of a squid tentacle and the bending behavior of octopus arms or elephant
      trunks.

PMID- 16580022
TI  - Mathematical modeling of ovarian cancer treatments: sequencing of surgery and
      chemotherapy.
AB  - Ovarian cancer has long been one of the most common forms of cancer in women. The
      main treatment for ovarian cancer comprises a combination of surgery and
      chemotherapy. In an effort to improve treatment strategies, a variety of
      mathematical models have been developed in the literature. In this paper, we
      consider a simple mathematical model that incorporates tumor growth as well as
      the effects of chemotherapeutic and surgical treatments in ovarian cancer. We
      consider several growth models and combine them with different cell-kill
      hypotheses. Surgery is assumed to eliminate a fixed fraction of tumor cells
      instantaneously. We discuss how different models predict the optimal sequencing
      of chemotherapeutic and surgical treatments. This work has been carried out in
      the context of ovarian cancer; however, the results may also be useful for other
      kind of cancers.

PMID- 16580023
TI  - Age-related decline of dopamine synthesis in the living human brain measured by
      positron emission tomography with L-[beta-11C]DOPA.
AB  - Loss of dopamine synthesis in the striatum with normal human aging has been
      observed in the postmortem brain. To investigate whether there is age-associated
      change in dopamine synthesis in the extrastriatal brain regions similar to that
      in the striatum, positron emission tomography studies with (11)C-labelled l-DOPA
      were performed on 21 normal healthy male subjects (age range 20-67 years).
      Decline in the tissue fraction of gray matter per region of interest was also
      investigated. The overall uptake rate constant for each region of interest was
      quantified by the Patlak plot method using the occipital cortex as reference
      region. Regions of interest were set on the dorsolateral prefrontal cortex,
      lateral temporal cortex, medial temporal cortex, occipital cortex, parietal
      cortex, anterior cingulate, thalamus, midbrain, caudate nucleus, and putamen.
      Test-retest analysis indicated good reproducibility of the overall uptake rate
      constant. Significant age-related declines of dopamine synthesis were observed in
      the striatum and extrastriatal regions except midbrain. The decline in the
      overall uptake rate constant was more prominent than in the tissue fraction of
      gray matter. These results indicate that the previously demonstrated age-related
      decline in striatal dopamine synthesis extends to several extrastriatal regions
      in normal human brain.

PMID- 16580024
TI  - The distribution and sources of heavy metals in Izmit Bay surface sediments
      affected by a polluted stream.
AB  - Dil Deresi stream is a highly contaminated stream passing through the most
      heavily industrialized area of Izmit Bay. In this research, surface sediments in
      the <63-microm fraction collected from 34 sites at western part of Izmit Bay,
      Northeastern Marmara Sea, Turkey were analyzed by ICP-AES for Al, As, Cd, Co, Cr,
      Cu, Fe, Mg, Mn, Ni, Pb, Sn and Zn. Metal concentrations were compared with the
      marine sediment quality standards (SQS) and literature data to assess the
      pollution status of the sediments. Enrichment factors (EFs) were calculated to
      assess whether the concentrations observed represent background or contaminated
      levels. The analysis revealed three groups of elements: (1) Sn is the most
      enriched element; (2) As, Cd, Pb and Zn are minor enriched elements; and (3) Co,
      Cr, Cu, Fe, Mg, Mn and Ni are at background concentrations. The distribution maps
      of the concentrations and enrichment factors for all heavy metals were also
      produced as a contour plot based on Geographic Information System (GIS)
      technology.

PMID- 16580025
TI  - Detecting the cytogenetic effects in workers occupationally exposed to
      vincristine with four genetic tests.
AB  - To study the human genetic damage induced by vincristine (VCR), the cytogenetic
      effects in workers occupationally exposed to vincristine were studied with
      micronucleus (MN) test, comet assay, hypoxantinepho-guanine phosphoribosyl
      transferase (hprt) gene mutation assay and T-cells receptor (TCR) gene mutation
      assay. Fresh peripheral blood samples were collected from the workers and
      controls. Fifteen workers from a plant producing antineoplastic drug
      (vincristine) and 15 controls were matched according to age, gender and smoking.
      The results of MN test showed that the mean micronuclei rate (MNR) and mean
      micronucleated cells rate (MCR) in 15 workers were 17.80+/-1.88 per thousand and
      13.67+/-1.56 per thousand, respectively, which were significantly higher than
      those (3.73+/-0.80 per thousand and 3.13+/-0.59 per thousand) in controls
      (P<0.01). It was found in the comet assay that the mean tail length (MTL) of 15
      workers and 15 controls were 1.72+/-0.15 microm and 0.71+/-0.01 microm,
      respectively, there was significant difference between workers and controls for
      MTL (P<0.05), but the difference between the mean tail moment (MTM, 0.29+/-0.03)
      of 15 workers and MTM (0.17+/-0.05) of 15 controls was not significant (P>0.05).
      The results of hprt gene mutation assay showed that the average mutation
      frequency of hprt (Mf-hprt) in workers was 1.03+/-0.02 per thousand, which was
      significantly higher than that (0.87+/-0.01 per thousand) in controls (P<0.05).
      Meanwhile, the results of TCR gene mutation assay indicated that Mfs-TCR of
      workers and controls were 2.52+/-0.34 x 10(-4) and 1.51+/-0.11 x 10(-4),
      respectively, there was a significant difference between workers and controls
      (P<0.01). It is found in the results of our study that the genetic damage is
      detectable in 15 workers occupationally exposed to vincristine.

PMID- 16580026
TI  - Reinforcing effects of nicotine microinjections into the ventral tegmental area
      of mice: dependence on cholinergic nicotinic and dopaminergic D1 receptors.
AB  - We used an intracranial self-administration (ICSA) procedure to assess the
      involvement of the ventral tegmental area (VTA) nicotinic receptors in the
      rewarding effects of nicotine. We then challenged intra-VTA nicotine self
      administration via systemic or local injections of dopamine (DA)-D1 and nicotinic
      receptor antagonists. C57BL/6J mice were stereotaxically implanted unilaterally
      with a guide cannula above the VTA. After 1 week of recovery, mice were allowed
      to discriminate between two arms of a Y-maze over seven daily sessions, one arm
      being reinforced by intracranial nicotine microinjection. Mice exhibited nicotine
      self-administration at both doses tested, i.e. 10 ng (21.6 pmol) and 100 ng (216
      pmol)/50-nl injection. In contrast, mice receiving a 216-pmol nicotine dose 0.8
      mm above VTA performed at chance level. Once the ICSA response was acquired,
      systemic pretreatment with the DA-D1 receptor antagonist SCH 23390 (25 microg/kg
      i.p.) or co-infusion of the nAChR antagonist DHbetaE with nicotine disrupted
      ICSA. Replacement of SCH 23390 by vehicle, or withdrawal of DHbetaE from
      nicotine/DHbetaE mixed solutions led to recovery of intra-VTA nicotine self
      administration. We conclude that nicotinic receptors in the VTA, presumably
      alpha4beta2 nAChRs are critically to mediate the rewarding effects of nicotine
      and that DA-D1 receptors are also directly implicated.

PMID- 16580027
TI  - Multimodal similarity and categorization of novel, three-dimensional objects.
AB  - Similarity has been proposed as a fundamental principle underlying mental object
      representations and capable of supporting cognitive-level tasks such as
      categorization. However, much of the research has considered connections between
      similarity and categorization for tasks performed using a single perceptual
      modality. Considering similarity and categorization within a multimodal context
      opens up a number of important questions: Are the similarities between objects
      the same when they are perceived using different modalities or using more than
      one modality at a time? Is similarity still able to explain categorization
      performance when objects are experienced multimodally? In this study, we
      addressed these questions by having subjects explore novel, 3D objects which
      varied parametrically in shape and texture using vision alone, touch alone, or
      touch and vision together. Subjects then performed a pair-wise similarity rating
      task and a free sorting categorization task. Multidimensional scaling (MDS)
      analysis of similarity data revealed that a single underlying perceptual map
      whose dimensions corresponded to shape and texture could explain visual, haptic,
      and bimodal similarity ratings. However, the relative dimension weights varied
      according to modality: shape dominated texture when objects were seen, whereas
      shape and texture were roughly equally important in the haptic and bimodal
      conditions. Some evidence was found for a multimodal connection between
      similarity and categorization: the probability of category membership increased
      with similarity while the probability of a category boundary being placed between
      two stimuli decreased with similarity. In addition, dimension weights varied
      according to modality in the same way for both tasks. The study also demonstrates
      the usefulness of 3D printing technology and MDS techniques in the study of
      visuohaptic object processing.

PMID- 16580028
TI  - When true memory availability promotes false memory: evidence from confabulating
      patients.
AB  - We explored the extent to which confabulators are susceptible to false recall and
      false recognition, and whether false recognition is reduced when memory for
      studied items is experimentally enhanced. Five confabulating patients, nine non
      confabulating amnesics--including patients with (F amnesics) and without frontal
      lobe dysfunction (NF amnesics)--and 14 control subjects underwent the DRM
      paradigm [Roediger, H. L., & McDermott, K. B. (1995). Creating false memories:
      Remembering words not presented in lists. Journal of Experimental Psychology:
      Learning, Memory and Cognition, 21, 803-814.] in two experimental conditions. In
      both conditions participants studied eight lists of semantic associates, and free
      recall was tested after the presentation of each list. In the Standard condition
      recognition was tested after the presentation of all the lists, whereas in the
      Proximal condition patients were administered a six-item recognition task after
      the presentation of each list. Participants also provided remember or know
      judgements, and described the content of their recollections. All groups of
      patients recalled a lower proportion of targets and critical lures than did
      control subjects, but confabulators recalled more words unrelated to the studied
      lists than did NF amnesics and controls. All groups of participants improved true
      recognition across conditions. However, whereas normal controls suppressed false
      recognition to critical lures in the Proximal compared to the Standard condition,
      and non-confabulating amnesics showed comparable gist-based false recognition,
      confabulators showed increased levels of false recognition to critical lures
      across conditions. Furthermore, NF amnesics significantly reduced false
      recognition to unrelated lures in the Proximal compared to the Standard
      condition, whereas confabulators were unable to suppress false recognition to
      unrelated lures across conditions. Analysis of the phenomenological experience
      showed that, unlike non-confabulating amnesics, confabulators characterized true
      and false memories with irrelevant information related to test items. Results are
      interpreted in light of confabulators' monitoring deficits.

PMID- 16580029
TI  - Deficits in achromatic phantom contour perception in poor readers.
AB  - In a previous study [Sperling, A. J., Lu, Z. L., Manis, F. R., & Seidenberg, M.
      S. (2003). Selective deficits in magnocellular processing: A "phantom contour"
      study. Neuropsychologia, 41, 1422-1429] we found that dyslexic children were
      relatively slower in processing achromatic phantom contours. The maximum temporal
      frequency at which they could identify achromatic phantom contours was correlated
      with reading ability and orthographic skill in particular. Here we investigated
      whether similar deficits could be identified in adults. Poor readers were chosen
      who scored below the 25th percentile on either a standardized test of word
      identification or nonword pronunciation. Good readers were chosen who scored
      above the 40th percentile on both reading tasks. We replicated the findings of
      the child study: poor readers had slower processing in the achromatic version of
      the task, but not in the chromatic version. Achromatic performance correlated
      with several measures of reading and reading-related skills, including exception
      word reading and phonological awareness. We discuss the possibility that the
      deficits may indicate impairment in noise exclusion that is more readily apparent
      at higher temporal frequencies.

PMID- 16580030
TI  - Differential effects of lipopolysaccharide in the social behavior of dominant and
      submissive mice.
AB  - Acutely infected animals show a set of non-specific behavioral changes known as
      sickness behavior. Recent studies have shown that occurrence of sickness behavior
      is regulated according to a motivational perspective. Thus, the display of
      sickness behavior may compete with display of other behaviors. In this work, we
      sought to determine the effects of lipopolysaccharide (LPS) administration (15
      microg/mouse i.p.) in the social behavior of dominant and submissive mice.
      Results showed that social hierarchy influences the expression of sickness
      behavior. While dominant mice treated with LPS showed an expected reduction in
      total frequency of behaviors displayed, such decrease did not happen following
      the same treatment to submissive mice. Similar results occurred regarding social
      and aggressive behavior. The use of a motivational perspective provides the
      assumption that, due to their high social ranking, dominant mice were able to
      prioritize recuperative behavior. Submissive mice, on the other hand, even though
      treated with LPS, seemed to essentially focus on social defensive behaviors since
      they remained in the presence of the dominant individuals. Effects of sickness on
      the hierarchical organization of mice remain to be further investigated.

PMID- 16580031
TI  - There's no place like home: cage odours and place preference in subordinate CD-1
      male mice.
AB  - Prior studies using mice have shown that scent marks are an important source of
      information and can cause behavioural changes in other individuals. Studies have
      also shown that scent marks in the environment can affect the outcome of social
      interactions between mice. We used conditioned place preference tests to
      investigate whether CD-1 male mice (Mus musculus) are reinforced by olfactory
      cues from the home cage. Soiled bedding from the home cage was presented in the
      initially less preferred chamber of the apparatus to determine whether this
      association would reduce the unconditioned preference for one chamber over the
      other. We tested the effects of social rank and housing condition by comparing
      the performance of dyads that were polarised into dominant and subordinate
      relationships, both when paired and when separated, with mice that were isolated
      throughout. The development of conditioned place preference (CPP) supported by
      home cage odours was influenced by social rank but not by housing condition. Only
      subordinate mice showed CPP to home cage odours, and this effect was seen
      irrespective of whether they were housed with a dominant cage mate or alone.
      Neither dominant (paired or separated) nor isolated mice showed any change in
      their preference for the chamber associated with home cage odours. This suggests
      that the smell of home is a more powerful reinforcer for subordinate mice in that
      it can produce contextual conditioning to the environment in which it is
      experienced.

PMID- 16580032
TI  - The enigma of behavioral inputs to the circadian clock: a test of function using
      restraint.
AB  - Wheel running stimulated during the daily rest period can acutely shift circadian
      rhythms in Syrian hamsters. Spontaneous running, defining the active phase of the
      circadian rest-activity cycle, can shorten the circadian periodicity in constant
      light or dark in several nocturnal rodent species. The adaptive significance of
      these behavioral effects on pacemaker phase and period is unclear. Here we
      consider a hypothesis that behavioral inputs to the circadian pacemaker serve
      primarily to enhance the precision of light-dark entrainment and maintain daily
      activity onset close to lights-off (i.e., dusk) by stabilizing entrainment on a
      steeper portion of the delay zone of the phase-response curve to light. This
      hypothesis rests on the evidence that spontaneous activity early in the active
      period feeds back on the pacemaker to advance its motion. If so, then preventing
      activity at this time should induce a phase delay shift. Such delay shifts have
      been reported in Syrian hamsters physically restrained early in the active
      period. We show here that restraint can induce phase delays but that, using the
      Aschoff Type 2 procedure for measuring shifts, these delays are very small, are
      inversely related to behavioral sleep during restraint, and are positively
      correlated with 'rebound' increases in running following restraint, at a
      circadian time when stimulated running is known to induce phase delay shifts.
      Repeated bouts of restraint, to promote habituation, were associated with strong
      attenuation of 'rebound' running and no significant delay shifts. These results
      suggest that, in Syrian hamsters, spontaneous activity early at night has little
      effect on pacemaker motion, and argue against the stated hypothesis.

PMID- 16580033
TI  - Metabolic effects of spices, teas, and caffeine.
AB  - Consumption of spiced foods or herbal drinks leads to greater thermogenesis and
      in some cases to greater satiety. In this regard, capsaicin, black pepper,
      ginger, mixed spices, green tea, black tea and caffeine are relevant examples.
      These functional ingredients have the potential to produce significant effects on
      metabolic targets such as satiety, thermogenesis, and fat oxidation. A
      significant clinical outcome sometimes may appear straightforwardly but also
      depends too strongly on full compliance of subjects. Nevertheless, thermogenic
      ingredients may be considered as functional agents that could help in preventing
      a positive energy balance and obesity.

PMID- 16580034
TI  - Dynamic pathway allocation in early terpenoid biosynthesis of stress-induced lima
      bean leaves.
AB  - Two independent pathways contribute in higher plants to the formation of
      isopenteny1 diphosphate (IDP), the central building block of isoprenoids. In
      general, the cytosolic mevalonate pathway (MVA) provides the precursors for
      sesquiterpenes and sterols, whereas the plastidial methylerythritol pathway (MEP)
      furnishes the monoterpene-, diterpene- and carotenoids. Administration of
      deuterium labeled 1-deoxy-d-xylulose and mevalolactone to lima beans (Phaseolus
      lunatus), followed by gas chromatographic separation and mass spectrometric
      analysis of de novo produced volatiles revealed that the strict separation of
      both pathways does not exist. This could be confirmed by blocking the pathways
      individually with cerivastatin((R)) (MVA) and fosmidomycin (MEP), respectively.
      Isotopic ratio mass spectrometry (IRMS) at natural abundance levels demonstrated
      independently and without the need for labeled precursors a dynamic allocation of
      the MVA- or the MEP-pathway in the biosynthesis of the nerolidol-derived
      homoterpene 4,8-dimethy1-nona-1,3,7-triene (DMNT). Insect-feeding upregulated
      predominantly the MVA-pathway, while the fungal elicitor alamethicin stimulated
      the biosynthesis of DMNT via the MEP-pathway.

PMID- 16580035
TI  - Secondary metabolites from Senecio burtonii (Compositae).
AB  - A cacalolide derivative named 4alpha-[2'-hydroxymethylacryloxy]-1beta-hydroxy-14
      (5-->6) abeo eremophilan-12,8-olide and a shikimic acid derivative named (3'E)
      (1alpha)-3-hydroxymethyl-4beta,5alpha-dimethoxycyclohex-2-enyloctadec-3'-enoate
      along with three known compounds, octacosan-1-ol, 3beta-hydroxyolean-12-en-28-oic
      acid and 3beta-acetoxyolean-12-en-28-oic acid were isolated from Senecio
      burtonii. Their structures and relative configurations were established on the
      basis of spectroscopic analysis.

PMID- 16580036
TI  - Steroid hydroxylations with Botryodiplodia malorum and Colletotrichum lini.
AB  - An improved procedure for the microbial hydroxylations of dehydroepiandrosterone
      (DHEA, 1) and 15 beta,16 beta-methylene-dehydroepiandrosterone (2) was studied
      using whole cells of Botryodiplodia malorum and Colletotrichum lini. C. lini
      catalyzed 7 alpha- and 15 alpha-hydroxylation of 1 and 7 alpha-hydroxylation of
      2, while B. malorum gave 7 beta-hydroxylation of both the substrates. The
      stability of the enzymatic activity was higher in the presence of co-substrates
      (i.e., glucose or mannitol) allowing for repeated batches of the
      biotransformations. The yields of 7 alpha,15 alpha-dihydroxy-1 production were
      improved obtaining 5.8 gl(-1) (recovered product) from 7.0 gl(-1) of substrate.
      The structures of the hydroxylated products were assigned by a combination of two
      dimensional NMR proton-proton and proton-carbon correlation techniques.

PMID- 16580037
TI  - Modeling observation error and its effects in a random walk/extinction model.
AB  - This paper examines the consequences of observation errors for the "random walk
      with drift", a model that incorporates density independence and is frequently
      used in population viability analysis. Exact expressions are given for biases in
      estimates of the mean, variance and growth parameters under very general models
      for the observation errors. For other quantities, such as the finite rate of
      increase, and probabilities about population size in the future we provide and
      evaluate approximate expressions. These expressions explain the biases induced by
      observation error without relying exclusively on simulations, and also suggest
      ways to correct for observation error. A secondary contribution is a careful
      discussion of observation error models, presented in terms of either log
      abundance or abundance. This discussion recognizes that the bias and variance in
      observation errors may change over time, the result of changing sampling effort
      or dependence on the underlying population being sampled.

PMID- 16580038
TI  - Control of cellular proliferation by modulation of oxidative phosphorylation in
      human and rodent fast-growing tumor cells.
AB  - The relationship between cell proliferation and the rates of glycolysis and
      oxidative phosphorylation in HeLa (human) and AS-30D (rodent) tumor cells was
      evaluated. In glutamine plus glucose medium, both tumor lines grew optimally.
      Mitochondria were the predominant source of ATP in both cell types (66-75%),
      despite an active glycolysis. In glucose-free medium with glutamine,
      proliferation of both lines diminished by 30% but oxidative phosphorylation and
      the cytosolic ATP level increased by 50%. In glutamine-free medium with glucose,
      proliferation, oxidative phosphorylation and ATP concentration diminished
      drastically, although the cells were viable. Oligomycin, in medium with glutamine
      plus glucose, abolished growth of both tumor lines, indicating an essential role
      of mitochondrial ATP for tumor progression. The presumed mitochondrial inhibitors
      rhodamines 123 and 6G, and casiopeina II-gly, inhibited tumor cell proliferation
      and oxidative phosphorylation, but also glycolysis. In contrast, gossypol,
      iodoacetate and arsenite strongly blocked glycolysis; however, they did not
      affect tumor proliferation or mitochondrial metabolism. Growth of both tumor
      lines was highly sensitive to rhodamines and casiopeina II-gly, with IC(50)
      values for HeLa cells lower than 0.5 microM, whereas viability and proliferation
      of human lymphocytes were not affected by these drugs (IC(50) > 30 microM).
      Moreover, rhodamine 6G and casiopeina II-gly, at micromolar doses, prolonged the
      survival of animals bearing i.p. implanted AS-30D hepatoma. It is concluded that
      fast-growing tumor cells have a predominantly oxidative type of metabolism, which
      might be a potential therapeutic target.

PMID- 16580040
TI  - Begomovirus genetic diversity in the native plant reservoir Solanum nigrum:
      Evidence for the presence of a new virus species of recombinant nature.
AB  - We examined the native plant host Solanum nigrum as reservoir of genetic
      diversity of begomoviruses that cause the tomato yellow leaf curl disease (TYLCD)
      emerging in southern Spain. Presence of isolates of all the species and strains
      found associated with TYLCD in this area was demonstrated. Mixed infections were
      common, which is a prerequisite for recombination to occur. In fact, presence of
      a novel recombinant begomovirus was demonstrated. Analysis of an infectious clone
      showed that it resulted from a genetic exchange between isolates of the ES strain
      of Tomato yellow leaf curl Sardinia virus and of the type strain of Tomato yellow
      leaf curl virus. The novel biological properties suggested that it is a step
      forward in the ecological adaptation to the invaded area. This recombinant
      represents an isolate of a new begomovirus species for which the name Tomato
      yellow leaf curl Axarquia virus is proposed. Spread into commercial tomatoes is
      shown.

PMID- 16580039
TI  - Polybrominated diphenyl ether (PBDE)-induced alterations in vitamin A and thyroid
      hormone concentrations in the rat during lactation and early postnatal
      development.
AB  - In experimental animals fed standard laboratory diets, penta-BDE mixtures can
      decrease circulating thyroid hormone and liver vitamin A concentrations. A
      substantial number of pregnant women and their children have marginal vitamin A
      status, potentially increasing their risk of adverse effects to penta-BDE
      exposure. The current study investigated the effects of maternal gestational and
      lactational penta-BDE exposure on thyroid hormone and vitamin A homeostasis in
      rats of sufficient vitamin A (VAS) or marginal vitamin A (VAM) status and their
      offspring. Dams were administered daily oral doses of 18 mg/kg DE-71 (a penta-BDE
      mixture) or a corn oil vehicle from gestation day 6 through lactation day (LD)
      18. Thyroid hormone and vitamin A homeostasis were assessed in plasma and tissues
      of LD 19 dams and postnatal day (PND) 12, 18, and 31 pups. DE-71 exposure induced
      hepatomegaly in VAS and VAM pups at all timepoints and increased testes weights
      at PND 31. While liver vitamin A concentrations were low in DE-71 treated dams
      and pups, plasma retinol concentrations and plasma retinol binding protein levels
      were only low in VAM animals exposed to DE-71. DE-71 exposure lowered plasma
      thyroxine concentrations in VAS and VAM dams and pups. Plasma thyroid stimulating
      hormone concentrations were high in VAM dams exposed to DE-71, suggesting that
      marginal vitamin A status enhances the susceptibility to thyroid hormone axis
      disruption by DE-71. These results support the concept that marginal vitamin A
      status in pregnant women may increase the risk for PBDE-induced disruptions in
      vitamin A and thyroid hormone homeostasis.

PMID- 16580042
TI  - The relative contributions of luminance contrast and task demands on saccade
      target selection.
AB  - Luminance contrast and spatial frequency have a strong effect on when saccades
      are initiated. In this study, we ask to what extent the internal contrast
      response determines where saccades are directed to. Observers signalled, with a
      manual button press, which of two patterns was of higher (Experiment 1) or lower
      (Experiment 2) contrast. Even though the visual stimuli were identical in both
      experiments, the pattern of first fixated items was very different. Saccade
      target selection largely reflected the task instructions, suggesting that
      luminance contrast can be used to rapidly and effectively guide the eyes to task
      relevant information.

PMID- 16580041
TI  - Evidence for elongated receptive field structure for mechanisms subserving
      stereopsis.
AB  - To study the spatial extent and shape of the binocular disparity mechanisms
      subserving depth perception, we employ the spatial summation paradigm of contrast
      threshold for front/back depth discrimination at a fixed binocular disparity. The
      stimuli were Gabor patches with disparity set at either 4 or 8 arcmin and spatial
      frequency set at an optimal value of 4 cy/deg. Contrast threshold was measured as
      a function of length and width of the Gabor patches to determine the aspect ratio
      of greatest efficiency. The space constant of the Gaussian envelope varied
      between 0.0375 degrees and 0.9 degrees in either vertical or horizontal
      directions, or both simultaneously. For vertical elongation of the Gabor patches,
      discrimination sensitivity improved by 4-6 dB for a doubling of the length of the
      Gabor patches, then reduced more slowly as the length further increased. However,
      extending the Gabor patches horizontally across cycles produced little or no
      sensitivity improvement. Instead, discrimination performance collapsed in a
      fashion that is incompatible with many models of disparity processing. The
      results imply that the main mechanisms subserving stereoscopic depth
      discrimination are vertically elongated for vertical-bar Gabors and encounter
      special difficulties integrating horizontal disparity information. Disparity
      discrimination sensitivity for very small targets was also much greater than
      predicted by the single-mechanism fit, implying the presence of a second,
      independent mechanism with a very small summation field, which may underlie the
      fine stereoscopic processing system.

PMID- 16580043
TI  - Electrochemical treatment of effluents containing Cr(VI). Influence of pH and
      current on the kinetic.
AB  - Compounds of Cr(VI) are very toxic and their reduction to Cr(III) is necessary to
      allow their further precipitation or adsorption. Chemical methods for Cr(VI)
      reduction are usually used for this purpose. As an alternative, electrochemical
      methods using three-dimensional electrodes, such as reticulated vitreous carbon
      (RVC) and polyaniline-modified RVC, have been used successfully. Since the pH
      affects reaction of Cr(VI) reduction, in this work its effect on the reaction
      rate was studied using electrodes of RVC and RVC/PANI. While a maximum in
      reaction rate was found for a pH 1.5 using the RVC, the RVC/PANI showed no
      differences in reaction rates in the range of pH between 0 and 1. Practically, no
      reaction was observed for any pH greater than 3. The effect of different current
      densities using optimized pH was also evaluated and the RVC/PANI electrode showed
      the best reaction rates, current efficiencies and energy consumption as a result
      of the polyaniline electrocatalytic effect.

PMID- 16580044
TI  - Distribution patterns of nitrobenzenes and polychlorinated biphenyls in water,
      suspended particulate matter and sediment from mid- and down-stream of the Yellow
      River (China).
AB  - Samples of water, suspended particulate matter (SPM) and sediment were collected
      from mid- and down-stream of the Yellow River. The distribution and concentration
      of 10 nitroaromatic compounds and polychlorinated biphenyls (PCBs) were
      extensively studied. The total concentration of 10 nitrobenzenes (SigmaNBs)
      varied from 0.269 to 9.052 microg l(-1) in water, from 2.916 to 164.4 microg kg(
      1) dry weight in SPM, and from 0.954 to 14.72 microg kg(-1) dry weight in
      sediment. PCBs associated with the sediments, measured as the summed responses of
      Aroclor 1242, 1248, 1254, 1260 (in comparison to those of a standard 1:1:1:1
      mixture), were found to be in the range of non-detectable to 5.98 microg kg(-1).
      In the samples collected, various PCB congeners showed similar distribution
      characteristics with congeners containing 3-5 chlorine atoms accounting for more
      than 96.4% of total PCB. In most of the samples, PCB concentrations occurred in
      the order: TetraCB > TriCB > PentaCB. Levels of SigmaNBs in the Yellow River were
      relatively low in comparison with values reported from other river and marine
      systems, and PCB levels were comparatively low. Relative to the PCBs, SigmaNBs
      showed significantly more difference among the various stations, presumably due
      to the influence of different pollution sources. No obvious correlation was
      observed between the pollutant concentrations and either the TOC or the grain
      size of the sediments.

PMID- 16580045
TI  - Dissipation of polycyclic aromatic hydrocarbons from soil added with manure or
      vermicompost.
AB  - The dissipation of three PAHs, i.e., 500 mg phenanthrene kg(-1) soil, 350 mg
      anthracene kg(-1) soil and 150 mg benzo(a)pyrene kg(-1) soil, was investigated in
      soil from Acolman (Mexico) added with cow manure or vermicompost while production
      of CO(2) and inorganic N was monitored. At day 0, recovery of added phenanthrene
      was 95%, anthracene 96% and benzo(a)pyrene 100% in sterilized soil and
      concentrations did not change significantly in sterilized soil over time.
      Application of organic material did not affect the concentration of phenanthrene
      and anthracene, which decreased sharply in the unsterilized soil in the first
      weeks of the incubation. Less than 3% of the added phenanthrene was detected
      after 100 days and less than 8.5% of the added anthracene (mean of the two
      experiments). The decrease in concentration of benzo(a)pyrene (BaP) was not fast
      as that of phenathrene and anthracene, and 22% was extractable from soil still
      after 100days. It was concluded that addition of farm yard manure (FYM) and
      vermicompost only had an effect on the initial dissipation of phenanthrene,
      anthracene and benzo(a)pyrene in soil of Acolman.

PMID- 16580046
TI  - A linked spatial and temporal model of the chemical and biological status of a
      large, acid-sensitive river network.
AB  - Freshwater sensitivity to acidification varies according to geology, soils and
      land-use, and consequently it remains difficult to quantify the current extent of
      acidification, or its biological impacts, based on limited spot samples. The
      problem is particularly acute for river systems, where the transition from acid
      to circum-neutral conditions can occur within short distances. This paper links
      an established point-based long-term acidification model (MAGIC) with a landscape
      based mixing model (PEARLS) to simulate spatial and temporal variations in
      acidification for a 256 km(2) catchment in North Wales. Empirical relationships
      are used to predict changes in the probability of occurrence of an indicator
      invertebrate species, Baetis rhodani, across the catchment as a function of
      changing chemical status. Results suggest that, at present, 27% of the river
      network has a mean acid neutralising capacity (ANC) below a biologically-relevant
      threshold of 20 microeq l(-1). At high flows, this proportion increases to 45%.
      The model suggests that only around 16% of the stream network had a mean ANC < 20
      microeq l(-1) in 1850, but that this increased to 42% at the sulphur deposition
      peak around 1970. By 2050 recovery is predicted, but with some persistence of
      acid conditions in the most sensitive, peaty headwaters. Stream chemical
      suitability for Baetis rhodani is also expected to increase in formerly acidified
      areas, but for overall abundance to remain below that simulated in 1850. The
      approach of linking plot-scale process-based models to catchment mixing models
      provides a potential means of predicting the past and future spatial extent of
      acidification within large, heterogeneous river networks and regions. Further
      development of ecological response models to include other chemical predictor
      variables and the effects of acid episodes would allow more realistic simulation
      of the temporal and spatial dynamics of ecosystem recovery from acidification.

PMID- 16580047
TI  - Monitoring and modelling the impacts of global change on European freshwater
      ecosystems.

PMID- 16580048
TI  - Groundwater contamination from well points -- an experience from the Norwegian
      groundwater monitoring network.
AB  - Until 2005 the observation wells of the Norwegian Groundwater Monitoring Network
      in Quaternary aquifers were equipped with metal well points with brass lining. A
      laboratory leaching test using a new well point demonstrated that the well point
      material (galvanized iron pipe), the brass lining and the solder used to fix the
      lining could cause substantial contamination of the collected well water with a
      long list of chemical elements (Sn, Zn, Pb, Sb, Cd, Fe, Cu, Mn and Al), depending
      on well capacity, contact time water/well point and pH. Because groundwater
      chemistry is receiving increased attention in groundwater monitoring all wells
      were equipped with high density polyethylene (HDPE) points during the years 2004
      2005. The HDPE points did not return any values above detection in a similar
      leaching test, with some minor values of Zn being the only exception.

PMID- 16580049
TI  - Linked models to assess the impacts of climate change on nitrogen in a Norwegian
      river basin and FJORD system.
AB  - Dynamically downscaled data from two Atmosphere-Ocean General Circulation Models
      (AOGCMs), ECHAM4 from the Max-Planck Institute (MPI), Germany and HadAm3H from
      the Hadley Centre (HAD), UK, driven with two scenarios of greenhouse gas
      emissions (IS92a and A2, respectively) were used to make climate change
      projections. These projections were then used to drive four effect models linked
      to assess the effects on hydrology, and nitrogen (N) concentrations and fluxes,
      in the Bjerkreim river basin (685-km(2)) and its coastal fjord, southwestern
      Norway. The four effect models were the hydrological model HBV, the water quality
      models MAGIC, INCA-N and the NIVA FJORD model. The downscaled climate scenarios
      project a general temperature increase in the study region of approximately 1
      degrees C by 2030-2049 (MPI IS92a) and approximately 3 degrees C by 2071-2100
      (HAD A2). Both scenarios imply increased winter precipitation, whereas the
      projections of summer and autumn precipitation are quite different, with the MPI
      scenario projecting a slight increase and the HAD scenario a significant
      decrease. As a response to increased winter temperature, the HBV model simulates
      a dramatic reduction of snow accumulation in the upper parts of the catchment,
      which in turn lead to higher runoff during winter and lower runoff during
      snowmelt in the spring. With the HAD scenario, runoff in summer and early autumn
      is substantially reduced as a result of reduced precipitation, increased
      temperatures and thereby increased evapotranspiration. The water quality models,
      MAGIC and INCA-N project no major changes in nitrate (NO(3)(-)) concentrations
      and fluxes within the MPI scenario, but a significant increase in concentrations
      and a 40-50% increase in fluxes in the HAD scenario. As a consequence, the
      acidification of the river could increase, thus offsetting ongoing recovery from
      acidification due to reductions in acid deposition. Additionally, the increased N
      loading may stimulate growth of N-limited benthic algae and macrophytes along the
      river channels and lead to undesirable eutrophication effects in the estuarine
      area. Simulations made by the FJORD model and the HAD scenario indicate that
      primary production in the estuary might increase up to 15-20%, based on the
      climate-induced changes in river flow and nitrate concentrations alone.

PMID- 16580050
TI  - Biomagnification of PBDEs and PCBs in food webs from the Baltic Sea and the
      northern Atlantic Ocean.
AB  - Biomagnification of polychlorinated biphenyls (PCBs) and polybrominated
      diphenylethers (PBDEs) in food webs from the Baltic Sea and the northern Atlantic
      Sea was investigated. For this, we used PCB and PBDE concentration data, together
      with data on fish body weight and delta15N of fish and zooplankton as a measure
      of trophic position. In the Baltic Sea material, consisting of zooplankton,
      sprat, herring and salmon, we report biomagnification of all PCB congeners but
      PCB #209 and of PBDEs with 3-6 or 7 bromine atoms. Higher brominated PBDEs and
      PCB 209 did not biomagnify likely due to their high molecular weights or sizes
      and subsequent inefficient dietary uptake in fish. If salmon was excluded from
      the statistical analysis, strong biomagnification of PCB #209 was evident,
      indicating species differences in biomagnification. In the Baltic Sea material
      delta15N and body weight covaried. In the Atlantic Sea material, consisting of
      fish samples (herring and salmon) of larger body sizes, we show positive
      correlation between concentrations of most PCBs and PBDEs and body weight without
      increasing delta15N. This shows that biomagnification in some cases depends on
      body size and not trophic position. We conclude that there probably is trophic
      position dependence in biomagnification, which was manifested in a food chain
      from zooplankton to piscivores, but no further trophic position influence on
      biomagnification in fish at the highest trophic levels. In these fish, there was
      a body size effect leading to biomagnification, probably due to slower clearance
      in larger fish. PCB concentrations were generally between 2 and 6 times higher in
      Baltic Sea salmon than in Atlantic Sea salmon. Higher PBDE concentrations in the
      Baltic compared to the Atlantic Sea salmon were also found, but with a larger
      variation between congeners. Nona- to deca-BDEs were found in most investigated
      samples, which illustrates the bioavailability of these compounds. Unidentified
      penta-, hexa-, hepta-, and octa- BDEs were found in several samples.

PMID- 16580051
TI  - Aluminum dynamics in forest soil waters in Norway.
AB  - We report on weekly aluminum (Al) concentration measurements in soil water from
      forested catchments monitored throughout Norway since 1986. Originating in
      acidification research, and thus accompanied by many other chemical variables,
      they constitute a comprehensive data set suited for analysis of short- as well as
      long-term variations in a geographic perspective. The Al time series at 21 sites
      are characterized by high temporal variability, seasonal behavior, and episodic
      events with peak values in the range 200-800 micromol/l, mostly caused by sea
      salts blown inland in storms, with a subsequent release of Al after cation
      exchange. Despite a clear south-north gradient in possible acidification over
      Norway, we found no indication of such south-north trends in Al chemistry,
      neither in mean values, maximum values, nor time trends. We identified two main
      drivers for variation in Al concentrations. The first one was sea salts, where Al
      was released to the soil solution after cation exchange. The second driver was
      high production of DOC, where Al was driven into the soil solution by
      complexation with DOC. There appears to be little risk for aluminum toxicity to
      trees in Norwegian forests. Except during occasional episodes, aluminum
      concentrations generally lay far below the supposed threshold values for toxic
      effects on Norway spruce, Scots pine and birch. Much dissolved aluminum was non
      labile, and thus relatively non-toxic. Although the Ca2+/labile Al ratio was
      often below 1.0, considerable doubt exists as to the applicability of this
      variable in the field.

PMID- 16580052
TI  - Increasing serum levels of non-DDT-derivative organochlorine pesticides in the
      younger population of the Canary Islands (Spain).
AB  - Organochlorine pesticides are a lipophilic class of chemicals that persist in the
      environment and tend to accumulate in human tissues for years. They came into
      widespread use in the late 1940s. Because of their capacity to bioaccumulate and
      biomagnify in food chains and their toxic effects, most of them were banned in
      industrialized countries, among them Spain, in the late 1970s and 1980s. In 1998
      organochlorine pesticides were determined in a representative sample of a Spanish
      population (around 690 serum samples from people 6 to 75years old from the Canary
      Islands). Serum levels of lindane aldrin, dieldrin and endrin, were determined.
      Our results showed that a high percentage of samples presented detectable levels
      of some of the organochlorines measured, endrin being the most frequently
      detected (72%) and at highest concentration (mean 136.7ng/g fat). Mean
      concentrations of the main cyclodiene evaluated, dieldrin, was lower to those
      found in other Western populations. However, serum levels of lindane were higher
      than those described in North European populations. Influence of geographical and
      sociodemographic factors was evaluated. Urban populations showed the highest
      levels of dieldrin, while non-urban population showed the highest serum values of
      lindane, aldrin and endrin. Unexpectedly, serum values of lindane, aldrin and
      dieldrin were higher in younger than in older people. Subjects under 18years
      showed almost twice as high serum levels of lindane, aldrin and dieldrin than
      subjects of 65-75years. These results may well suggest that people living in the
      Canary Islands have been and are currently exposed to non-DDT-organochlorine
      pesticides. The type and source of exposure could vary between islands and type
      of habitat. Contaminated food and/or the environment could be related with this
      situation.

PMID- 16580053
TI  - Prophylaxis and von Willebrand's disease (vWD).
AB  - Von Willebrand disease (vWD) is an inherited bleeding disorder with a prevalence
      of approximately 1% in the general population. The bleeding occurs in this
      disorder primarily because of abnormalities in platelet adhesion, due to a
      primary deficiency or defect in the von Willebrand factor (vWF) often with a
      concomitant decrease in factor VIII (FVIII) levels. The mainstay of treatment for
      the majority of patients with vWD is desmopressin, which releases vWF from
      endothelial cells. For patients in which desmopressin is neither suitable or
      recommended, coagulation factor concentrates containing both vWF with FVIII are
      the alternative therapeutic option for controlling bleeding. Joint disease is an
      uncommon but disabling complication of vWD. The arthropathy results from
      recurrent bleeding into a joint, with the ankle and hip being the joints most
      often affected, particularly in patients with type 3 vWD. Without adequate
      treatment, persistent bleeding into joints can result in pain, joint
      degeneration, swelling and loss of range of motion (ROM). There is some evidence
      to suggest that joint bleeding and subsequent joint damage might be prevented by
      early prophylaxis. A soon to open clinical trial by the Von Willebrand Disease
      Prophylaxis Network (vWD PN) aims to further explore this treatment concept. This
      article addresses the prophylaxis of vWD, with a particular focus on joint
      disease.

PMID- 16580054
TI  - Adverse effects of ultraviolet radiation: a brief review.
AB  - Solar ultraviolet radiation (UVR) has always been part of the environment of man.
      UVB is required for the conversion of 7-deoxycholesterol to vitamin D, which is
      critically important in the maintenance of healthy bones and research is making
      clear that it has other potential roles in maintenance of human health. Exposure
      to UVR, whether of solar or artificial origin, also carries potential risks to
      human health. UVR is a known carcinogen and excessive exposure-at least to solar
      radiation in sunlight-increases risk of cancer of the lip, basal cell, and
      squamous cell carcinoma of the skin and cutaneous melanoma, particularly in fair
      skin populations. There is also evidence that solar UVR increases risk of several
      diseases of the eye, including cortical cataract, some conjunctival neoplasms,
      and perhaps ocular melanoma. Solar UVR may also be involved in autoimmune and
      viral diseases although more research is needed in these areas. Artificial UVR
      from tanning beds, welding torches, and other sources, may contribute to the
      burden of disease from UVR. This brief review will assess the human evidence for
      adverse health effects from solar and artificial UVR and will attempt to assign a
      degree of certainty to the major disease-exposure relationships based on the
      weight of available scientific evidence.

PMID- 16580055
TI  - Risks and benefits of sun exposure: implications for public health practice based
      on the Australian experience.
AB  - Over recent years, evidence has been accumulating that vitamin D has a positive
      impact on our overall health. This may have an impact on the future of our public
      health advice related to skin cancer prevention. This paper explores, from a
      public health perspective based on Australian experience, how skin cancer
      prevention messages should be managed in light of new information about vitamin D
      and, in particular, the times when sun protection advice should be provided and
      how the vitamin D message can be complementary to the sun protection message.

PMID- 16580056
TI  - The potentiating effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      on paraquat-induced neurochemical and behavioral changes in mice.
AB  - Although the etiology of Parkinson's disease (PD) is not fully understood, there
      are numerous studies that have linked the increased risk for developing PD to
      pesticides exposure including paraquat (PQ). Moreover, the exposure to a
      combination of compounds or chemical mixtures has been suggested to further
      increase this risk. In the current study, the effects of PQ on the nigrostriatal
      dopaminergic system in male C57BL6 mice exposed to 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) were examined to assess the impact of toxic substance
      mixtures exposure on neurochemical and behavioral changes. In this study, a low
      non-toxic dose of MPTP (10mg/kg) was injected once a day for 5 days and was
      followed by PQ (7 mg/kg) once a day for 6 days (subacute protocol) or once a week
      for 10 weeks (chronic protocol). The results from the subacute protocol showed
      that PQ reduced the turnover of dopamine (DA) as indicated by a 21% and a 22.3%
      decrease in dihydroxyphenyl acetic acid (DOPAC), homovanillic acid and increased
      S-adenosyl methionine/S-adenosyl homocysteine index (SAM/SAH) by 100%. However,
      the administration of PQ to MPTP primed mice resulted in the decrease of DOPAC,
      HVA, DA, by 35.8%, 35.2% and 22.1%, respectively. In addition, PQ decreased the
      total number of movements (TM) by 28% but MPTP plus PQ decreased TM by 41%. The
      SAM/SAH index showed that MPTP increased methylation by 33.3%, but MPTP plus PQ
      increased methylation by 81%. In the chronic protocol, the data showed that MPTP
      administration did not affect DA, DOPAC, and HVA levels. The administration of PQ
      led to significant decrease in DOPAC, HVA, and TD by 31.6%, 19.9%, and 21.2%
      respectively with no effect on DA levels. The MPTP plus PQ group showed reduced
      DA, DOPAC, HVA, and total distance traveled by 58.4%, 82.8%, 55.8%, and 83.9%,
      respectively. Meanwhile, PQ administration caused a reduction in tyrosine
      hydroxylase immunoreactivity in the substantia nigra, and this effect was more
      pronounced in MPTP pretreated mice. It was concluded from this study that prior
      treatment with MPTP potentiated the effects of PQ in reducing DA, DOPAC, HVA, TH
      immunoreactivity, locomotor activity, and increasing the methylation index. The
      enhanced effects of PQ following MPTP administration further support the role of
      toxic substance mixtures in causing Parkinson's disease.

PMID- 16580057
TI  - Role of glutamate receptors in the ventromedial hypothalamus in the regulation of
      female rat sexual behaviors. II. Behavioral effects of selective glutamate
      receptor antagonists AP-5, CNQX, and DNQX.
AB  - Bilateral infusions of glutamate or its selective ionotrophic receptor agonists
      to the ventromedial hypothalamus (VMH) produce a rapid inhibition of both
      appetitive and consummatory sexual behavior in hormone-primed female rats. The
      present study examined whether infusion of selective ionotrophic glutamate
      receptor antagonists to the VMH can facilitate female sexual behavior in females
      treated with estradiol benzoate (EB) and progesterone (P), or EB alone.
      Ovariectomized, sexually experienced female rats were implanted bilaterally with
      guide cannulae aimed at the ventrolateral VMH. After recovery from surgery,
      females were primed either with EB+P or EB alone, and infused with saline, or one
      of two doses each of AP-5 (to target NMDA receptors), CNQX, or DNQX (to target
      AMPA/kainate receptors), immediately before tests with sexually vigorous male
      rats in bilevel chambers. In general, the drug infusions had a more powerful
      effect in females primed with EB alone compared to females primed with EB+P. AP-5
      increased lordosis in females primed with EB alone. CNQX had a similar
      facilitative effect on lordosis, and also increased solicitations. DNQX increased
      solicitations in both hormone-priming conditions, increased lordosis quotients
      and magnitudes, and decreased pacing and defensive responses in the EB-alone
      condition. These results indicate that antagonism of glutamate receptors in the
      VMH resembles the effect of P, and that the addition of P to an EB baseline
      eliminates most of the effects of glutamate receptor antagonists. These data
      support the notion that glutamate receptors in the VMH contribute a strong
      inhibitory influence in the control of female sexual behavior.

PMID- 16580058
TI  - Measuring exposure to environmental tobacco smoke (ETS): a developing country's
      perspective.
AB  - AIMS: To assess exposure to ETS among nonsmokers in the community and examine the
      relation between various subjective and objective measures of exposure to ETS in
      a developing country's setting. METHODS: An interviewer-administered population
      based survey of adults 18-65 years residing in Aleppo, Syria. From a total number
      of 2038 participants, a sub-sample of 419 nonsmokers (27.2% men, 72.8% women,
      mean age 34 years) underwent subjective and objective assessment of exposure to
      ETS (saliva cotinine, breath CO, self-reported measures of exposure combined into
      ETS exposure scale). RESULTS: Overall, 97.6% of adults nonsmokers assessed in
      this study, 72.9% of whom were women, have detectable saliva cotinine levels
      (mean +/- SD 1.7 +/- 1.5 ng/ml). Correlation between self-reported exposure
      measures and saliva cotinine was moderate with the strongest observed for number
      of cigarette smokers in the house, average number of cigarettes smoked daily in
      the house, house policy regarding smoking, and total ETS score (r 0.3-0.4). These
      same variables were among the best predictors of saliva cotinine according to
      stepwise linear regression analysis, but their individual relevance differed
      between men and women reflecting underlying differences in gender-based behavior
      mobility patterns. Generally, subjective measures could explain 22% of the
      variability in cotinine levels in men and 19% in women. CONCLUSIONS: Exposure to
      ETS is universal among adult nonsmokers in Syria. Saliva cotinine correlated
      moderately with self-reported measures, whereby selected subjective measures can
      be as informative as composite scores incorporating multiple measures. Even in
      this environment of omnipresence of smoking, household restrictions seem to offer
      protection against ETS exposure.

PMID- 16580059
TI  - Impact of a multimedia intervention "Skinsafe" on patients' knowledge and
      protective behaviors.
AB  - BACKGROUND: Rates of malignant melanoma are rising, with those people with sun
      sensitive skin most at risk. Health education interventions are needed to help
      people protect themselves by detecting early signs of melanoma and by protecting
      their skin from sunburn. This study aimed to evaluate the impact of an
      interactive multimedia intervention "Skinsafe" on patients' knowledge about
      melanoma and on their skin protective behaviors. METHODS: In this cluster
      randomized, controlled trial conducted in Nottinghamshire, UK, doctors and nurses
      in 5 family practices prescribed Skinsafe to patients with higher risk skin
      characteristics. Measures of melanoma knowledge, perceived risk of melanoma and
      reported skin protective behaviors were obtained at baseline and at 6-month
      follow-up from 259 patients receiving the intervention and 330 patients with
      higher risk skin characteristics in 5 matched control practices. RESULTS AND
      DISCUSSION: Participants had low levels of melanoma knowledge at baseline. At
      follow-up, the intervention group had higher knowledge scores than control (3.71
      vs. 3.03, P < or = 0.001), reported more protective skin behaviors (5.36 vs.
      5.06, P = 0.007) and were more likely to report mole checking (odds ratio 1.67,
      95% CI 1.04 to 2.70, P = 0.035). The Skinsafe intervention was evaluated
      positively by patients and could be used to support melanoma health education
      within clinical settings.

PMID- 16580060
TI  - Effectiveness of administration of gonadotropin-releasing hormone at Days 11, 14
      or 15 after anticipated ovulation for increasing fertility of lactating dairy
      cows and non-lactating heifers.
AB  - One strategy for improving fertility in cattle is mid-cycle administration of
      GnRH to increase progesterone secretion and delay luteolysis. This strategy might
      be especially useful during hot weather because heat stress increases uterine
      prostaglandin release and reduces development of the elongating embryo. A series
      of experiments was conducted to test the efficacy of GnRH for increasing
      fertility. There was no effect of administration of 100 microg GnRH at Day 11
      after anticipated ovulation on pregnancy rates in virgin heifers subjected to
      timed artificial insemination (TAI) during the summer. Similarly, there was no
      beneficial effect of administration of GnRH at Day 11 after anticipated ovulation
      on pregnancy rates of lactating cows subjected to TAI in summer and winter. Three
      experiments tested effects of injection of GnRH at Days 14 or 15 after
      anticipated ovulation on pregnancy rates of lactating cows. The first experiment
      used 477 lactating cows subjected to TAI. Cows receiving GnRH at Day 14 had
      higher pregnancy rates in both summer and winter than cows receiving vehicle
      (20.3 versus 12.7%, P<0.02). When this experiment was repeated during summer with
      137 cows, there was a negative effect of GnRH treatment at Day 14 on pregnancy
      rate. In the third experiment, lactating cows during summer were inseminated at
      detected estrus and cows were assigned to treatment with either GnRH or vehicle
      at Days 14 or 15 after insemination. Pregnancy rates were 25.6% (32/125) for cows
      receiving vehicle, 20.7% (19/92) for cows receiving GnRH at Day 14, and 20.3%
      (16/79) for cows receiving GnRH at Day 15. In conclusion, GnRH administration at
      Days 11-15 after anticipated ovulation or estrus did not consistently increase
      pregnancy rates in either cool or warm seasons.

PMID- 16580061
TI  - Sexual characteristics of domestic queens kept in a natural equatorial
      photoperiod.
AB  - The objective of this study was to describe the sexual characteristics of
      domestic queens kept under natural equatorial photoperiod conditions without
      mating. Estrous signs were detected in 25 pubertal queens by manual stimulation
      and by exposure to a tomcat twice daily for 6 months (January to June). The signs
      observed were tail deflection, spinal flexion, rubbing or rolling, vaginal
      discharge, vocalization, treading of the hind legs, body or tail tremor and
      rigidity, blow or scratches, and discomfort on manipulation. The queen was
      considered in estrous when neck grip, tail deflection and attempted penile
      intromission by the male were allowed after mounting. From 187 cycles, there were
      (mean +/- S.E.M.) 7.5 +/- 0.7 cycles detected per queen; the duration of the
      cycle, estrus and non-acceptance were 18.1 +/- 0.9, 7.9 +/- 0.5, and 10.3 +/- 0.9
      d, respectively. Queens always maintained some signs of sexual behaviour; they
      remained ambivalent for no more than 24 h at a time. It was noted that 85.3% of
      the observations of body or tail tremor and rigidity were made during estrus;
      therefore, these signs were considered characteristic of sexual receptivity.
      There was no evidence of prolonged anestrus or of a circannual pattern to estrus
      cyclicity.

PMID- 16580062
TI  - The effect of administering a dopamine agonist (Cabergoline) on follicular and
      luteal development during pro-estrus and estrus in the female greyhound.
AB  - To study the effect of the dopamine agonist Cabergoline, on ovarian activity in
      the female dog during pro-estrus and estrus, 6 greyhounds were treated with 5
      microg/kg per os of Cabergoline for 20 days beginning on the first day of pro
      estrus; 6 animals were left untreated (controls). Ovarian morphology was
      determined by ultrasound examination once a day during pro-estrus and twice a day
      during estrus. Follicles were divided into three classes on the basis of their
      diameter: F1 (<3mm), F2 (3-6mm) and F3 (>6mm). The presence and diameters of post
      ovulatory follicles (F-POST) and corpora lutea (CL) were also recorded. Blood
      samples were taken once a day during pro-estrus and twice a day during estrus.
      The plasma was assayed for LH, prolactin and progesterone by radioimmunoassay.
      There were no differences between Cabergoline-treated and control dogs in the
      duration of pro-estrus or estrus. There was a progressive increase in follicle
      diameter from the start of pro-estrus when follicles were mainly class F1 to the
      day of estrus when follicles were mainly class F3. Three days after the start of
      estrus, the first F-POST follicles were detected. This pattern of development
      continued and on day 5 the first CLs were detected. By day 9, only CLs were
      detected. The peak of pre-ovulatory LH was within 3 days of estrus and ovulation
      was detected in all animals within 3 days of the LH peak. There were no
      differences in LH concentrations between groups. Plasma prolactin levels varied
      between animals and were reduced in treated dogs, however, this was not
      statistically significant (P=0.12). Plasma progesterone levels were below 1.0
      ng/ml before the LH surge and thereafter gradually increased. There were no
      differences in plasma progesterone concentrations between treated and control
      dogs. In conclusion these results show that the administration of the dopamine
      agonist Cabergoline during pro-estrus and estrus did not affect the duration of
      pro-estrus or estrus or the pattern of follicular and luteal development in
      female dogs.

PMID- 16580063
TI  - Porogen-induced surface modification of nano-fibrous poly(L-lactic acid)
      scaffolds for tissue engineering.
AB  - In addition to suitable pore architecture of a tissue-engineering scaffold,
      surface modification after scaffolding fabrication is often needed to enhance the
      interactions between cells and the synthetic material. In this study, a novel one
      step process was developed to fabricate surface-modified nano-fibrous poly(L
      lactic acid) (NF-PLLA) scaffolds. First, gelatin spheres with smooth surface were
      prepared by non-surfactant emulsification, solvent extraction, and freeze-drying.
      A three-dimensional NF-PLLA scaffold was then fabricated by using gelatin spheres
      as porogen. Gelatin molecules were entrapped onto the scaffold surface during the
      fabrication process. Attenuated total reflectance-Fourier transform infrared
      spectroscopy (ATR-FTIR) spectroscopy and X-ray photoelectron spectroscopy
      analysis demonstrated the existence of gelatin molecules on the surface of the
      polymer scaffold. The amount of gelatin on the scaffold surface was controlled by
      the composition of the solvent mixture of gelatin solution. The compressive
      modulus of scaffold prepared with gelatin spheres was more than three times
      higher than that prepared with irregular gelatin particles of the same size
      range. The surface modification significantly improved initial cell adhesion and
      proliferation over a 2-week culture. SEM images indicated that cells spread on
      the gelatin-entrapped scaffolds in contrast to spherical or spindle morphology on
      the control 1 day after cell seeding. Furthermore, more matrix secretion was
      observed on the surface-modified scaffolds than on the control after 2 weeks of
      in vitro cultivation. In conclusion, this approach provides a simple one-step
      process to fabricate surface-modified collagen-like NF-PLLA scaffolds, which have
      improved cell adhesion and proliferation.

PMID- 16580064
TI  - Influence of surface pretreatment of titanium- and cobalt-based biomaterials on
      covalent immobilization of fibrillar collagen.
AB  - Collagen type-I is a major component of the extracellular matrix of most tissues
      and it is increasingly utilized for surface engineering of biomaterials to
      accelerate receptor-mediated cell adhesion. In the present study, coatings with
      layers of fibrillar type-I collagen were prepared on titanium, titanium alloy,
      and cobalt alloy to improve initial osteoblast adhesion and implant-tissue
      integration. To suppress the quick in vivo degradation rate of collagen the
      deposited layers were covalently immobilized at the metal surfaces as well as
      chemically cross-linked. The application of different oxidation techniques to the
      metallic substrates resulted in surfaces with varying hydroxyl group contents,
      which directly influenced the amount of immobilized silane coupling agents. It
      was found that a high density of surface-bound coupling agents increased the
      stability of the covalently linked collagen layers. After coating of metallic
      biomaterials with a cross-linked collagen layer, an improved cellular response of
      human osteoblast-like cells (MG-63) in vitro could be recognized.

PMID- 16580065
TI  - The effect of environmental factors on the response of human corneal epithelial
      cells to nanoscale substrate topography.
AB  - We have previously shown that human corneal epithelial cells sense and react to
      nanoscale substrate topographic stimuli [Teixeira AI, Abrams GA, Bertics PJ,
      Murphy CJ, Nealey PF. Epithelial contact guidance on well-defined micro- and
      nanostructured substrates. J Cell Sci 2003;116(10):1881-92; Karuri NW, Liliensiek
      S, Teixeira AI, Abrams G, Campbell S, Nealey PF, et al. Biological length scale
      topography enhances cell-substratum adhesion of human corneal epithelial cells. J
      Cell Sci 2004;117(15):3153-64]. Here we demonstrate that cellular responses to
      nanoscale substrate topographies are modulated by the context in which these
      stimuli are presented to cells. In Epilife medium, cells aligned preferentially
      in the direction perpendicular to nanoscale grooves and ridges. This is in
      contrast to a previous study where cells cultured in DMEM/F12 medium aligned in
      the direction parallel to nanoscale topographic features [Teixeira AI, Abrams GA,
      Bertics PJ, Murphy CJ, Nealey PF. Epithelial contact guidance on well-defined
      micro- and nanostructured substrates. J Cell Sci 2003;116(10):1881-92].
      Additionally, cell alignment in Epilife medium was dependent on pattern pitch.
      Cells switched from perpendicular to parallel alignment when the pitch was
      increased from 400 to 4,000 nm. There was a transition region (between 800 and
      1,600 nm pitch) where both parallel and perpendicular alignments were favored
      compared to all other cellular orientations. Cells formed focal adhesions
      parallel to the substrate topographies in this transition region. On the nano-
      and microscale patterns, 400 and 4,000 nm pitch, focal adhesions were almost
      exclusively oriented obliquely to the topographic patterns.

PMID- 16580066
TI  - Implantation, embryo-maternal interactions, immunology and modulation of the
      uterine environment -- a workshop report.
AB  - The Workshop discussed five topics which were considered to be topical. 1) A
      comparison was made between rodents and primates regarding how uNK cells are
      distributed at the implantation site in these species. 2) The possibility that
      the functions of uNK cells may be different in mice and humans are discussed. 3)
      Trophoblast MHC expression in the Rhesus monkey (haemochorial) and the sheep
      (epitheliochorial) was compared in order the gauge the importance of these
      molecules in these two fundamentally different types of placentation. 4) New data
      were presented on the intriguing molecule, HLA-G, whose function is still
      unclear. 5) A discussion was initiated to debate the role of the innate and the
      adaptive immune systems in human implantation.

PMID- 16580068
TI  - Addition of sargramostim (GM-CSF) to imatinib results in major cytogenetic
      response in a patient with chronic myeloid leukemia.
AB  - Imatinib mesylate, an inhibitor of BCR/ABL tyrosine kinase, has remarkable
      activity in chronic myeloid leukemia resulting in an 87% major cytogenetic
      response. We describe a woman who failed to achieve any cytogenetic response
      after 2.5 years of imatinib, 400mg daily. When daily sargramostim (GM-CSF) 100
      microg/m2 was added, cytogenetic studies revealed a gradual increase in
      percentage of normal cells from start, 4, 9, and 15 months at 0%, 10%, 55%, and
      85%, respectively. She became transfusion independent after starting GM-CSF. The
      addition of GM-CSF to imatinib resulted in a clinical benefit and a major
      cytogenetic response in this patient.

PMID- 16580067
TI  - Endothelium, blood vessels and angiogenesis -- a workshop report.

PMID- 16580069
TI  - Predictive abilities of numerical sediment quality guidelines in Sydney Harbour,
      Australia, and vicinity.
AB  - Matching chemical and toxicological data of surficial sediments from Sydney
      Harbour, Australia, and vicinity, were collected to evaluate predictive abilities
      of Effects Range-Low (ERL), Effects Range-Median (ERM) and other sediment quality
      guidelines (SQGs). Samples (n=103) containing a wide range of chemicals and
      concentrations were subjected to a battery of 4-6 toxicity tests. ERLs and
      functionally equivalent low-range SQGs were highly predictive of non-toxicity
      when not exceeded, as incidences of toxicity were 0-8%. ERMs and other mid-range
      SQGs were predictive of toxicity in combined test data with > or = 80% of toxic
      samples with one or more SQG exceeded. Predictive abilities of mid-range SQGs
      were low for amphipod survival tests (generally < 20% toxic samples), but the
      incidence of toxicity increased with increasing numbers of SQGs exceeded and
      increasing mean SQG quotients. Predictive abilities of SQGs generally matched
      their narrative intent when outcomes of multiple toxicity tests were considered,
      and were consistent with North American data. Functionally equivalent SQGs gave
      comparable results (except where developed for single chemical classes),
      indicating that predictive abilities were primarily influenced by sensitivities
      of test species and/or the bioavailability of contaminants.

PMID- 16580070
TI  - Comparison of some trace elements concentration in blood, tumor free breast and
      tumor tissues of women with benign and malignant breast lesions: an Indian study.
AB  - Fifty women residing in and around New Delhi, India and identified to have benign
      (25 nos.) and malignant (25 nos.) breast lesions were studied for the first time
      to access the association between environmental exposure to lead and risk of
      breast cancer and to determine the potential of changes in trace elements
      concentration as a diagnostic marker and/or its etiological involvement in the
      disease. Blood, tumor tissue and breast adipose tissue from tumor free area from
      each patient of the two groups, collected at the time of lumpectomy or mastectomy
      (only blood sample was collected from disease free control group), were analyzed
      to determine the concentration of Pb, Zn, Cu, Fe and Ca using Atomic Absorption
      Spectrometry. Blood lead was significantly higher in malignant cases than in
      those of benign and control (p<0.05 each). Lead level was also higher in tumor
      tissue when compared with their respective normal tumor free breast tissue,
      though non-significant, in both benign and malignant cases. Interestingly, Zn,
      Fe, and Ca levels were higher in blood of malignant cases than in those of their
      benign counterparts. Furthermore, these metals were also higher in tumor of
      malignant and benign cases as compared to normal tumor free breast tissue, many
      of them statistically significant (p<0.05/0.01/0.001). However, Cu level was
      insignificantly lower in the blood and tumor tissue of malignant cases when
      compared with their benign counterparts while it was significantly higher
      (p<0.05) in tumor of benign cases when compared with those of their respective
      normal tumor free breast tissue. There were statistically significant
      correlations between lead and trace element levels only in normal tumor free
      breast tissue of benign and malignant cases (r=0.41-0.73; p<0.05-0.001) but
      neither in blood nor tumor tissue of the two groups. These results suggest that
      in the backdrop of existing experimental and epidemiological evidences exposure
      to lead may be one of the risk factors for breast lesions; though it warrants
      further investigation. Further, modulation of trace elements level in both benign
      and malignant breast diseases patients may be of potential to be used as
      diagnostic marker of the disease process and its possible relationship
      etiologically.

PMID- 16580071
TI  - IgE cross-reactivity between the major peanut allergen Ara h 2 and tree nut
      allergens.
AB  - Allergy to peanut and tree nuts is characterised by a high frequency of life
      threatening anaphylactic reactions and typically lifelong persistence. Although
      peanut is the most common cause of nut allergy, peanut allergic patients are
      frequently also sensitive to tree nuts. It is not known if this is due to cross
      reactivity between peanut and tree nut allergens. In this study, the major peanut
      allergen Ara h 2 was cloned from peanut cDNA, expressed in E. coli cells as a His
      tag fusion protein and purified using a Ni-NTA column. Immunoblotting, ELISA and
      basophil activation indicated by CD63 expression all confirmed the IgE reactivity
      and biological activity of rAra h 2. To determine whether or not this allergen
      plays a role in IgE cross-reactivity between peanut and tree nuts, inhibition
      ELISA was performed. Pre-incubation of serum from peanut allergic patients with
      increasing concentrations of almond or Brazil nut extract inhibited IgE binding
      to rAra h 2. Purified rAra h 2-specific serum IgE antibodies also bound to
      proteins present in almond and Brazil nut extracts by immunoblotting. This
      indicates that the major peanut allergen, Ara h 2, shares common IgE-binding
      epitopes with almond and Brazil nut allergens, which may contribute to the high
      incidence of tree nut sensitisation in peanut allergic individuals.

PMID- 16580072
TI  - HIV-1 Vif protein blocks the cytidine deaminase activity of B-cell specific AID
      in E. coli by a similar mechanism of action.
AB  - HIV-1 Vif protein protects viral replication in non-permissive cells by inducing
      degradation of APOBEC3G via ubiquitination and proteasomal pathway, although new
      studies indicate a putative role in Vif's direct inhibition of APOBEC3G. APOBEC3G
      is member of a homologous family of proteins with cytidine deaminase activity
      expressed with characteristic tissue specificity, that in humans consist of
      APOBEC1, APOBEC2, APOBEC3A-H, APOBEC4 and the activation-induced deaminase (AID),
      a B lymphoid protein necessary for somatic hypermutation, gene conversion and
      class switch recombination. In this work we show that Vif can counteract AID's
      activity in E. coli in absence of specific eukaryotic co-factors necessary for
      AID induced somatic hypermutation, gene conversion and to stimulate class switch
      recombination in B-cells. We show that AID inhibition is mediated by a direct
      protein-protein interaction via unique amino acid D118 an homologous mutant
      responsible for the species-specific restriction of HIV-1 Vif protein existent
      for APOBEC3G. These results raise the hypothesis that Vif related proteins can
      act as a broad inhibitor of deaminase activity. Moreover as AID and Vif evolved
      in different cellular environments, these results may indicate that Vif related
      proteins might mimic cellular factors that interact with a structural conserved
      domain of cytidine deaminases during evolution.

PMID- 16580073
TI  - Impact of respiratory syncytial virus on hospital admissions in children younger
      than 3 years of age.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the main pathogen associated to
      acute respiratory infections (ARI) in children worldwide. OBJECTIVE: To determine
      the contribution of RSV to hospital admissions in children <3 years of age from
      May 2003 through April 2005 in San Luis Potosi, Mexico. METHODS: Cross-sectional
      survey of children <3 years of age admitted to a public general hospital and
      detection of RSV in respiratory secretions of children with ARI. RESULTS: There
      were 2036 children <3 years of age admitted to the hospital during the study
      period. The diagnosis at the time of admission was an ARI in 734 (36.1%)
      patients. RSV was detected in 153 (24.8%) of the 616 subjects who were tested.
      Children <1 year comprised 66% of admissions among children <3 years. RSV was
      detected in 26.9% of children with ARI <1 year; 21.5% of those 12-24 months of
      age and 15.25% of those 24-36 months old. CONCLUSIONS: RSV was associated to
      24.8% of ARI-related admissions in children <3 years of age. It is necessary to
      determine risk factors for RSV-related hospitalizations to evaluate the
      feasibility of establishing a preventive program for RSV infections in Mexico.

PMID- 16580074
TI  - Osteomyelitis of the ear canal caused by Staphylococcus lugdunensis.
AB  - Osteomyelitis of the temporal bone caused by Staphylococcus lugdunensis has never
      been reported before. This infection was diagnosed in a 51-year-old diabetic man.
      S. lugdunensis is an unusually virulent coagulase negative staphylococcus and has
      been implicated in a variety of severe infections. Considering the serious
      morbidity and mortality associated with osteomyelitis and in particular with S.
      lugdunensis, special awareness and alertness are required when otitis externa,
      which predisposes to osteomyelitis, is refractory to treatment.

PMID- 16580075
TI  - Use of DNA and recombinant canarypox viral (ALVAC) vectors for equine herpes
      virus vaccination.
AB  - In this study, experimental canarypox virus (ALVAC) and plasmid DNA recombinant
      vaccines expressing the gB, gC and gD glycoproteins of EHV-1 were assessed for
      their ability to protect conventional ponies against a respiratory challenge with
      EHV-1. In addition, potential means of enhancing serological responses in horses
      to ALVAC and DNA vaccination were explored. These included co-administration of
      the antigen with conventional adjuvants, complexation with DMRIE-DOPE and co
      expression of the antigen along with equine GM-CSF. Groups of EHV primed ponies
      were vaccinated twice intra-muscularly with one dose of the appropriate test
      vaccine at an interval of 5 weeks. Two to 3 weeks after the second vaccination,
      ponies were infected intra-nasally with the virulent Ab4 strain of EHV-1 after
      which they were observed clinically and sampled for virological investigations.
      The results demonstrated that DNA and ALVAC vaccination markedly reduced virus
      excretion after challenge in terms of duration and magnitude, but failed to
      protect against cell-associated viremia. Noteworthy was the almost complete
      absence of virus excretion in the group of ponies vaccinated with ALVAC-EHV in
      the presence of Carbopol adjuvant or DNA plasmid formulated with aluminium
      phosphate. The administration of the DNA vaccine in the presence of GM-CSF and
      formulated in DMRIE-DOPE and of the ALVAC vaccine in the presence of Carbopol
      adjuvant significantly improved virus neutralising antibody responses to EHV-1.
      These findings indicate that DNA and ALVAC vaccination is a promising approach
      for the immunological control of EHV-1 infection, but that more research is
      needed to identify the immunodominant protective antigens of EHV-1 and their
      interaction with the equine immune system.

PMID- 16580076
TI  - Is brain estradiol a hormone or a neurotransmitter?
AB  - Mounting evidence indicates that, besides their well-known hormonal mode of
      action at the genetic level, estrogens such as 17beta-estradiol also influence
      brain function by direct effects on neuronal membranes. Experimentally induced
      rapid changes in estradiol bioavailability in the brain have been shown to alter
      the expression of male sexual behavior significantly within minutes--probably too
      quickly to be accounted for by conventional genetic mechanisms. In parallel,
      recent studies indicate that aromatase, the enzyme that converts testosterone to
      estradiol in the brain, is expressed in presynaptic terminals and modulated
      within minutes by Ca(2+)-dependent phosphorylation. In this article, we develop
      the hypothesis that brain estrogens display many, if not all, functional
      characteristics of neuromodulators or even neurotransmitters.

PMID- 16580077
TI  - Cooling of the cerebellar interpositus nucleus abolishes somatosensory cortical
      learning-related activity in eyeblink conditioned rabbits.
AB  - Nictitating membrane movement and multiple-unit activity in the somatosensory
      cortex were recorded from rabbits during paired (N=6) and unpaired (N=5)
      presentations of a tone conditioned stimulus (CS) and an airpuff unconditioned
      stimulus (US). A behavioural conditioned response (CR) to the CS and an
      accompanying neural response in the somatosensory cortex developed only in the
      paired group. Inactivation of the cerebellar interpositus nucleus abolished both
      the acquired CR and the accompanying neural response. However, the CS facilitated
      both behavioural and neural responses to the US during the inactivation. Thus,
      the absence of the CR could not be accounted for by the general inability of the
      CS to alter the behaviour constituting the CR or the activity of the
      somatosensory cortex. These findings suggest that the efferent copy of the signal
      related to the eyeblink CR is projected from the cerebellum to the cerebral
      cortical areas of the US modality.

PMID- 16580078
TI  - Gender- and morphine dose-linked expression of spontaneous somatic opiate
      withdrawal in mice.
AB  - The opiate withdrawal syndrome powerfully motivates opiate seeking and abuse.
      Development of effective medications for opiate withdrawal symptoms is thus a
      primary research goal and heavily relies on improved experimental models. This
      study was carried out to establish a clinically relevant paradigm to assess
      somatic opiate withdrawal in mice. Female and male C57BL/6J mice were treated
      with saline or increasing morphine doses (10-50mg/kg or 20-100mg/kg) during 6
      consecutive days and tested for the spontaneous expression of somatic opiate
      withdrawal signs 8, 32, 56 and 80 h after last drug administration. Contrary to
      opioid receptor antagonist-precipitated procedures, the spontaneous opiate
      withdrawal paradigm used here revealed interesting gender- and morphine dose
      linked differences. In particular, 56 h after last morphine administration
      elevated global opiate withdrawal scores were still evident in female but not in
      male mice treated with 20-100mg/kg. The severity of somatic opiate withdrawal
      directly correlated with the prior cumulative morphine exposure. Timing of
      expression of somatic opiate withdrawal signs also varied as a function of both
      gender and morphine dose. For example, expression of paw tremors and wet dog
      shakes was earlier in opiate-withdrawn male than in female mice. Overall, these
      findings highlight the possibility to detect gender- and opiate dose-linked
      differences in the expression and duration of somatic opiate withdrawal using a
      clinically relevant research model. The behavioral paradigm described here may
      represent a more appropriate tool to investigate the neurobiological bases of
      opiate withdrawal as opposed to opioid receptor antagonist-precipitated opiate
      withdrawal procedures.

PMID- 16580079
TI  - Relative income, race, and mortality.
AB  - This paper examines the relationship between relative income and mortality. Our
      research is motivated by recent literature that posits that, holding individual
      income fixed, those whose income are low relative to the incomes of those in a
      reference group will have worse health. We develop an empirical model in which an
      individual's health is a function of his or her own income and the incomes of
      those who live in the same geographical area. We show how this individual-level
      model can be estimated using semi-aggregated data on the mortality rates of
      people categorized by age, race, gender, and place of residence. The model is
      estimated using mortality data from the 1980 and 1990 Compressed Mortality Files,
      merged with income data from the 1980 and 1990 5% Public Use samples of the US
      Census. We find no evidence that having relatively wealthy neighbors, holding own
      income fixed, is associated with higher mortality. Instead, we find evidence that
      among some demographic and age groups--in particular working-aged black males-
      having relatively wealthy neighbors is associated with lower mortality. For
      example, among younger (aged 25-64) black men, an increase in the income of
      others is estimated to have a beneficial effect on mortality that is 40% as large
      as an equivalent increase in own income.

PMID- 16580080
TI  - Long-term monitoring of biofilm growth and disinfection using a quartz crystal
      microbalance and reflectance measurements.
AB  - A biofilm reactor was constructed to monitor the long-term growth and removal of
      biofilms as monitored by the use of a quartz crystal microbalance (QCM) and a
      novel optical method. The optical method measures the reflectance of white light
      off the surface of the quartz crystal microbalance electrode (gold) for
      determination of the biofilm thickness. Biofilm growth of Pseudomonas aeruginosa
      (PA) on the surface was used as a model system. Bioreactors were monitored for
      over 6 days. Expressing the QCM data as the ratio of changes in resistance to
      changes in frequency (DeltaR/Deltaf) facilitated the comparison of individual
      biofilm reactor runs. The various stages of biofilm growth and adaptation to low
      nutrients showed consistent characteristic changes in the DeltaR/Deltaf ratio, a
      parameter that reflects changes in the viscoelastic properties of the biofilm.
      The utility of white light reflectance for thickness measurements was shown for
      those stages of biofilm growth when the solution was not turbid due to high
      numbers of unattached cells. The thickness of the biofilms after 6 days ranged
      from 48 mum to 68 mum. Removal of the biofilm by a disinfectant (chlorine) was
      also measured in real time. The combination of QCM and reflectance allowed us to
      monitor in real time changes in the viscoelastic properties and thickness of
      biofilms over long periods of time.

PMID- 16580081
TI  - Effect of allocating attention to aversive events on cardiovascular responses and
      event-related potentials in a dual-task paradigm.
AB  - This study investigated the effect of the allocation of attentional resources on
      event-related potentials (ERPs) and cardiovascular responses during a dual-task
      situation in which an avoidance task and a reward task were coupled. For the
      avoidance task, subjects were able to avoid an aversive shock that followed a
      target tone by pressing a button. For the reward task, subjects were asked to
      detect the direction of an arrowhead presented on the display screen and were
      rewarded for rapid, accurate reaction times. The 31 participants were divided
      into two groups based on their subjective impression of attention distribution
      between the avoidance and the reward task. Participants in the first group were
      motivated more by the avoidance task (AVD; n=18), whereas those in the second
      group were motivated more by the reward task (RWD; n=13). The ERPs to non-target
      and target tones, ECG, systolic blood pressure (SBP), and diastolic blood
      pressure (DBP) were analyzed in the dual-task situation. The results indicated
      that the amplitudes of N1 to target and non-target tones, and of N2 to the target
      tone were larger in the avoidance (AVD) group than they were in the reward (RWD)
      group. The AVD group had higher blood pressure than did the RWD group during the
      aversive periods. However, there were no significant group differences in the
      mean RTs for avoidance and reward tasks, and participants in both groups reported
      similar subjective evaluations of their mental workloads. The results suggest a
      vigilant coping strategy that selectively focus attention to threatening
      information as illustrated by N1 and N2 changes may intensify psychophysiological
      arousal under stress.

PMID- 16580082
TI  - Suppression on the mutagenicity of 4-nitroquinoline-N-oxide by the methanol
      extracts of soybean koji prepared with various filamentous fungi.
AB  - In this study, solid fermentation of soybean with various GRAS filamentous fungi
      including Aspergillus sojae BCRC 30103, Aspergillus oryzae BCRC 30222,
      Aspergillus awamori, Actinomucor taiwanesis and Rhizopus sp. was performed to
      prepare various soybean kojis. Toxicity, mutagenicity and suppression on the
      mutagenesis induced by a direct mutagen, 4-nitroquinoline-N-oxide (4-NQO) on
      Salmonella typhimurium TA 100, by the various methanol extracts of the prepared
      soybean koji and unfermented soybean were determined and compared. Results
      revealed that methanol extracts of unfermented soybean and kojis show no toxicity
      and mutagenic activity within the dose levels examined on test organism. On the
      other hand, antimutagenic activity against 4-NQO was observed with the extract of
      unfermented soybean. Furthermore, fermentation, regardless of the starter
      organism employed, resulted in an enhanced antimutagenic effect on the
      mutagenesis of 4-NQO by the extracts of the soybean koji. Across the dose range
      (0.625-5.0 mg/plate) tested, a dose-dependent antimutagenic activity was
      observed. Antimutagenic activities of the koji extracts varied with starter
      organism, with A. awamori-prepared koji extract exhibiting the highest rate of
      suppression on the mutagenicity of 4-NQO. Further study with A. awamori also
      revealed that fermentation temperature affected the antimutagenic activity of the
      prepared koji extract. In general, the extract of the A. awamori-soybean koji
      prepared at 30 degrees C showed a higher antimutagenic activity than those
      prepared at 25 or 35 degrees C.

PMID- 16580083
TI  - New multi-step kinetics using common affinity biosensors saves time and sample at
      full access to kinetics and concentration.
AB  - Today, affinity-based biosensorics is a standard technology in quantitative
      biomolecular interaction analysis, but suffers from low sample throughput and
      sometimes from inaccessible kinetics. A new methodology for such biosensors is
      introduced here that cuts down measurement time dramatically and increases
      confidentiality of results. In contrast to traditional applications, the ligand
      immobilized on the sensor chip is exposed to the binding analyte at a rapid
      stepwise change of the analyte concentration without the need for regenerations
      between analyte additions. In the application presented here, each addition of
      the analyte is succeeded by a buffer flow, yielding alternating association and
      dissociation phases in a "zigzag" style. This binding curve pattern is analyzed
      by means of novel fitting algorithms, which render detailed kinetics rate
      constants at a high level of self-consistency, and hence, validity due to
      multiple cross-checks. In comparison with traditional sequential kinetics
      analysis, this new multi-step kinetics approach returns practically identical (or
      improved) kinetics constants--at valuable savings in time/material since
      regeneration steps, ligand re-captures, or titration equilibrations are
      unnecessary.

PMID- 16580084
TI  - Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma
      following liver transplantation.
AB  - BACKGROUND/AIMS: Liver transplantation is an effective treatment for highly
      selected patients with hepatocellular carcinoma (HCC), but tumour recurrence
      remains an important cause of mortality. There are few data on the relation
      between the recurrence of HCC and lymphocytic infiltration following liver
      transplantation. METHODS: The tumour CD4+, CD8+, CD25+ and Foxp3+ lymphocyte
      infiltrate was assessed by immunohistochemistry in explant tissue of 69 patients
      who underwent liver transplantation for HCC between 1985 and 2001. The data were
      analysed according to HCC recurrence and factors known to be associated with
      outcome. RESULTS: Tumour size (Hazard ratio (95% CI: 1.19 (1.02, 1.39), P =
      0.03)), vascular invasion (P = 0.02), lymphocyte infiltration (P = 0.02) and
      CD4:CD8 ratio (P = 0.001) were identified as significant univariate predictors of
      tumour recurrence. On multivariate analysis CD4:8 ratio (P = 0.001), vascular
      invasion (P = 0.01), tumour size (P = 0.06) and reduced lymphocyte infiltration
      (P = 0.03) were significant independent predictors of recurrence. The presence of
      Foxp3+ T-lymphocytes was not predictive of recurrence, but was associated with
      vascular invasion (FE = 9.02, P = 0.04). CONCLUSIONS: The data support the
      hypothesis that immune responses are important in HCC and that the phenotype of
      infiltrating lymphocytes is informative regarding prognosis.

PMID- 16580085
TI  - Expression of CD44 in rat hepatic progenitor cells.
AB  - BACKGROUND/AIMS: Small hepatocytes (SHs) are hepatic progenitor cells, but the
      phenotypical difference between SHs and mature hepatocytes (MHs) has never been
      demonstrated. METHODS: The profile of gene expression was examined to clarify the
      difference between SHs and MHs by using a DNA microarray. Genes that were
      specifically expressed in SHs were identified and RT-PCR analysis of them was
      performed. Immunocytochemistry for CD44 standard form (CD44s) and variant form 6
      (CD44v6) was performed using cultured SHs and the d-galactosamine (GalN)-injured
      rat liver. From the GalN-treated liver, CD44s+ cells were obtained by sorting and
      RT-PCR analysis was performed. RESULTS: Analysis using the DNA microarray and RT
      PCR of them revealed restricted expression of CD44s and CD44v6 in SHs. In
      culture, CD44s appeared at day 3 and increased with the proliferation of SHs.
      CD44v6 expression was delayed compared to that of CD44s. With GalN
      administration, CD44+ hepatocytes appeared around periportal areas at days 3 and
      4 and then decreased. Sorted CD44s+ cells could form colonies and possessed
      hepatic markers. CONCLUSIONS: CD44 is a specific marker of SHs. The expression of
      CD44 mRNA and protein is restricted to SHs, and is up-regulated at the time when
      SHs start to proliferate both in vitro and in vivo.

PMID- 16580086
TI  - Enhanced ability of peripheral invariant natural killer T cells to produce IL-13
      in chronic hepatitis C virus infection.
AB  - BACKGROUND/AIMS: Human invariant natural killer T (iNKT) cells express a TCR
      Valpha24-JalphaQ paired with Vbeta11 and are activated by a surrogate ligand,
      alpha-galactosylceramide (alphaGalCer). The iNKT cells are involved in the
      regulation of anti-viral immune responses; however, little is known about their
      roles in hepatitis C virus (HCV) infection. METHODS: We compared the frequency of
      peripheral iNKT cells and their cytokine producing capacity reactive to
      alphaGalCer between chronically HCV-infected patients and healthy subjects.
      Cytokine production of freshly isolated iNKT cells were analyzed by ELISPOT.
      Activated iNKT cells were obtained by culture with alphaGalCer-loaded dendritic
      cells (DCs) and re-stimulated with them for the measurement of cytokine
      production. RESULTS: The frequencies of iNKT cells were not different between HCV
      infected patients and healthy subjects. The number of fresh IFN-gamma-producing
      iNKT cells reactive to alphaGalCer was not different between the patients and
      controls, whereas fresh iNKT cells produced negligible amounts of Th2 cytokines
      regardless of HCV infection. In response to alphaGalCer, expanded iNKT cells from
      the patients secreted IFN-gamma comparable in amount to controls, whereas they
      released significantly more IL-13 than cells from controls. CONCLUSIONS:
      Activated iNKT cells from HCV-infected patients gain more ability to secrete IL
      13 than those from healthy subjects.

PMID- 16580088
TI  - Giant localized fibrous tumours of the pleura: report of three subsequent cases.
AB  - Localized fibrous tumours of the pleura (LFTP) represent clinical entities rarely
      encountered, especially in giant forms. We report of three cases of giant
      localized fibrous tumours of the pleura found last year in a short time. The
      patients underwent surgery by thoracotomy. All tumours arose from visceral pleura
      and were radically excised by a wedge resection of the lung. The patients
      discharged from the hospital after a short postoperative period without
      complications. Two of three giant localized fibrous tumours were classified as
      benign forms; in one case a malignant characteristic was found.

PMID- 16580087
TI  - The diagnostic value of biomarkers (AshTest) for the prediction of alcoholic
      steato-hepatitis in patients with chronic alcoholic liver disease.
AB  - BACKGROUND/AIMS: The aim was to identify a panel of biomarkers (AshTest) for the
      diagnosis of alcoholic steato-hepatitis (ASH), in patients with chronic alcoholic
      liver disease. METHODS: Biomarkers were assessed in patients with an alcohol
      intake>50 g/d, in a training group, and in two validation groups. Diagnosis of
      ASH (polymorphonuclear infiltrate and hepatocellular necrosis) and its
      histological severity (four classes: none, mild, moderate and severe) were
      assessed blindly. RESULTS: Two hundred and twenty-five patients were included, 70
      in the training group, 155 in the validation groups, and 299 controls. AshTest
      was constructed using a combination of the six components of FibroTest-ActiTest
      plus aspartate aminotransferase. The AshTest area under the ROC curves for
      moderate-severe ASH was 0.90 in the training group, 0.88 and 0.89 in the
      validation groups. The median AshTest value was 0.005 in controls, 0.05 in
      patients without or with mild ASH, 0.64 in moderate, and 0.84 in severe ASH grade
      3, (P<0.05 between all groups). At a 0.50 cut-off, the sensitivity of AshTest was
      0.80 and the specificity was 0.84. CONCLUSIONS: In heavy drinkers, AshTest is a
      simple and non-invasive quantitative estimate of alcoholic hepatitis. The use of
      AshTest may reduce the need for liver biopsy, and therefore allow an earlier
      treatment of alcoholic hepatitis.

PMID- 16580089
TI  - Characterization and removal of DNAPL from sand and clay layered media.
AB  - Important characterization and remediation techniques (e.g. partitioning tracer
      tests (PTT), cosolvent and surfactant flushing) have been developed over the
      years to deal with dense nonaqueous phase liquid (DNAPL) sources in the saturated
      zone. Unfortunately, subsurface media layering and heterogeneity pose a major
      challenge to the efficiency of these and other techniques that rely on flushing
      fluids through porous media. Using laboratory column experiments with both single
      media and layered-media columns and computer modeling of tracer breakthrough
      results, we examined the difficulty that layering poses to subsurface remediation
      and characterization techniques. Quantifying tetrachloroethylene (PCE) saturation
      in layered media was determined using PTT and effluent mass determinations.
      Conservative tracer breakthrough curves were used to determine permeability and
      the flow through layers before and after PCE contamination. The removal
      efficiency of alcohol flushing in the layered systems was also determined.
      Results showed that even a relatively simple layering with less than an order
      magnitude difference in permeability leads to difficulty in characterization and
      remediation using flushing technologies. These results suggest that much greater
      volumes of flushing solutions will be needed in heterogeneous environments to
      ensure adequate flushing of lower permeable lenses and layers.

PMID- 16580090
TI  - Attitudes towards large numbers of choices in the food domain: a cross-cultural
      study of five countries in Europe and the USA.
AB  - Telephone interviews of 6000 representative adults from France, Germany, Italy,
      Switzerland, the UK, and the USA, included two items on attitudes to variety. One
      had to do with whether the respondent preferred a choice of 10 versus 50 ice
      cream flavors. Ten choices were preferred by a majority of respondents from each
      country except the United States. A second item asked whether one expected a
      small or large menu choice in an upscale restaurant. A majority in all countries
      expected the small number of choices, but this expectation was lowest in the UK
      and USA. High variety expectations and preferences were weakly positively
      correlated (r=0.19). There was no substantial relation between a variety of
      demographic variables and variety preferences or expectations, except that older
      people were less inclined to prefer the high (50) variety in ice cream choices
      (r=0.28). The results suggest that the US, and the UK to some extent, focus on
      providing choices that cater to individual differences in preferences, whereas
      the continental European countries are more attached to communal eating values.

PMID- 16580091
TI  - Peripheral ghrelin participates in the glucostatic signaling mediated by the
      ventromedial and lateral hypothalamus neurons.
AB  - Employing immunohistochemistry techniques, we examined the c-fos expression in
      different hypothalamic areas, when plasma glucose levels were modified by the
      administration of insulin and 2-deoxyglucose (2-DG) respectively. Subsequently,
      the hypoglycemia produced by an injection of insulin significantly increased
      feeding concomitant to higher c-fos expression in the arcuate nucleus (ARC),
      paraventricular nucleus (PVN), dorsomedial hypothalamus (DMH) and lateral
      hypothalamus (LH), while no statistical changes in the ventromedial hypothalamus
      (VMH) were found. Also, the glucopenia induced by 2-DG administration produced
      similar stimulatory effects on appetite and the neuronal activity affecting all
      the hypothalamic areas studied, including the VMH. The peripheral blockade of the
      orexigenic hormone ghrelin with a specific antibody (AGA) significantly decreased
      food intake as induced from acute hypoglycemia and glucopenia. Curiously, the
      conjoint AGA and insulin or 2-DG administration produced a differential effect on
      the hypothalamic neurons analyzed, by increasing the number of c-fos positive
      neurons in the ARC, PVN and DMH, but not in the VMH and LH. This outcome suggests
      an interactive effect of the glucostatic pathways involving these two areas with
      the ghrelin signaling.

PMID- 16580092
TI  - Rotenone induces cell death in primary dopaminergic culture by increasing ROS
      production and inhibiting mitochondrial respiration.
AB  - Although the definite etiology of Parkinson's disease is still unclear,
      increasing evidence has suggested an important role for environmental factors
      such as exposure to pesticides in increasing the risk of developing Parkinson's
      disease. In the present study, primary cultures prepared from embryonic mouse
      mesencephala were applied to investigate the toxic effects and underlying
      mechanisms of rotenone-induced neuronal cell death relevant to Parkinson's
      disease. Results revealed that rotenone destroyed dopaminergic neurons in a dose-
      and time-dependent manner. Consistent with the cytotoxic effect of rotenone as
      evidenced by dopaminergic cell loss, it significantly increased the release of
      lactate dehydrogenase into the culture medium, the number of necrotic cells in
      the culture and the number of nuclei showing apoptotic features. Rotenone exerted
      toxicity by decreasing the mitochondrial membrane potential, increasing reactive
      oxygen species production and shifting respiration to a more anaerobic state.

PMID- 16580093
TI  - Differential co-expression of AMPA receptor subunits in substance P receptor
      containing neurons of basal forebrain regions of C57/BL mice.
AB  - We are interested in cellular co-expression patterns of alpha-amino-3-hydroxy-5
      methyl-4-isoxazole-propionate (AMPA) receptor subunits 1-4 (GluR1-4) in substance
      P receptor (SPR)-containing neurons of the basal forebrain, which may act as a
      morphological basis for interaction between neurokinins and glutamate-driven
      neuronal signaling and excitotoxicity. Immunohistochemistry and laser scanning
      confocal microscopy in adult C57/BL mice revealed that distribution of SPR
      positive neurons overlapped with that of GluR1-4-containing ones in most basal
      forebrain regions, i.e. the medial septal nucleus, nucleus of diagonal band of
      Broca, magnocellular preoptic nucleus and substantia innominata. Neurons showing
      both SPR and GluR1-4-immunoreactivities were found in above cholinergic neurons
      rich containing basal forebrain regions. Semi-quantification analysis indicated
      that about 57-95% of SPR-positive neurons displayed GluR1-4-immunoreactivity. The
      percentages of AMPA receptor subunits co-localizing in SPR-positive neurons were
      GluR4 (48%), GluR1 (47%), GluR2 (26%) and GluR3 (20%), respectively. However, the
      neurons co-expressing SPR and GluR1-4 were hardly detected in the basal nucleus
      of Meynert of the basal forebrain. The co-localization of SPR and AMPA receptors
      has provided a molecular basis for functional interaction between neurokinins and
      AMPA receptors-mediated signaling in basal forebrain neurons. This study has also
      implied that glutamate-driven neuronal transmission and excitotoxicity can be
      modulated by neurokinin peptides in most basal forebrain regions but not in the
      basal nucleus of Meynert, suggesting that neurokinins or SP may play certain
      roles in determining neuronal functional properties or excitotoxic susceptibility
      in the various basal forebrain regions of mammals.

PMID- 16580095
TI  - Validation of clinical criteria for possible vascular dementia in the oldest-old.
AB  - Although vascular dementia (VaD) is a main pathology in nonagenarians and
      centenarians, the validity of clinical criteria for this diagnosis is unknown. We
      analyzed 110 autopsy cases and reported sensitivities and specificities of the
      State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC)
      and National Institute for Neurological Disorders and Stroke (NINDS-AIREN)
      criteria for possible VaD as well as Hachinski ischemic score (HIS). Among them,
      there were 36 neuropathologically confirmed VaD cases. All criteria displayed
      comparable sensitivities (0.56-0.58). Specificities values were 0.74, 0.73 and
      0.66, respectively. There was an age-related decrease on ADDTC criteria
      sensitivity due to the fact that 42% of pure VaD cases did not present with
      stroke. Thirty percent of mixed dementia (MD) cases were diagnosed as VaD by both
      NINDS-AIREN and ADDTC criteria. This proportion reached 45.9% for the HIS. These
      data demonstrate that the new diagnostic criteria for possible VaD do not provide
      a substantial gain of sensitivity compared to the HIS. Although their specificity
      was significantly lower in this age group compared to younger cohorts, all of
      them successfully exclude AD cases.

PMID- 16580094
TI  - BDNF mRNA expression and protein localization are changed in age-related hearing
      loss.
AB  - A decline in neuronal plasticity during the adult life span has been proposed to
      be associated with a reduced level of the effectors of plasticity responses
      (e.g., BDNF). Alteration of plasticity is also correlated with age-related
      hearing loss (presbycusis), but to date no detailed studies of BDNF expression
      have been performed in the young or aging mature cochlea. We have used rat and
      gerbil animal models for presbycusis, which displayed hearing loss in the final
      third of the animals' natural life span. We demonstrate for the first time a co
      localization of BDNF protein, transcripts III and IV in cochlear neurons with a
      declining distribution towards low-frequency processing cochlear turns. BDNF
      protein was also found within the neuronal projections of the cochlea. A
      significant reduction of BDNF transcripts in high-frequency processing cochlear
      neurons was observed during aging, though this did not coincide with a major
      reduction of BDNF protein. In contrast, BDNF protein in peripheral and central
      projections was drastically reduced. Our results suggest that reduced BDNF
      protein levels in auditory nerves over age may be a crucial factor in the altered
      brainstem plasticity observed during presbycusis.

PMID- 16580096
TI  - [Psychiatric adverse effects of fluoroquinolone: review of cases from the French
      pharmacologic surveillance database].
AB  - INTRODUCTION: Psychiatric adverse effects of fluoroquinolones are known for long,
      but can sometimes be missed. We analyse cases spontaneously reported to the
      French pharmacovigilance. METHODS: Cases of psychiatric adverse effects with
      fluoroquinolones reported to the French pharmacovigilance system were analysed.
      The studied period was from January 1985 and June 2002. Data analysed included
      age, sex, adverse effect, fluoroquinolone, seriousness and evolution. RESULTS:
      Five hundred ninety cases have been reported concerning 273 males and 316 females
      (sex unknown in 1 case). Mean age was 66 years (median: 70, range: 12-102). The
      most frequently reported psychiatric adverse effects were confusion (51%),
      hallucinations (27%), agitation (13%), delusion (12%), insomnia (8%), somnolence
      (4%) (several adverse effects could be associated in a single patient). Serious
      cases represented 21.7% (resulting in hospitalisation in most cases). Evolution
      was favourable in most cases (88.5%), and was unknown in 9.5% of cases.
      CONCLUSION: The number of cases reported during this period is moderate, but
      under-reporting probably interferes. The eventuality of this kind of adverse
      effect with fluoroquinolones should be kept in mind. Dose should be adjusted to
      renal function, especially in older patients.

PMID- 16580097
TI  - Mucosal genetic immunization against four adhesins protects against
      Staphylococcus aureus-induced mastitis in mice.
AB  - Staphylococcus aureus is the most common etiologic agent of mastitis in bovines
      and a major cause of economic losses in the dairy industry. Since adhesins, that
      anchor bacteria to the extracellular matrix (ECM), are among the most important
      S. aureus virulence factors, we used four adhesion factors (fibrinogen binding
      protein, fibronectin binding protein A, clumping factor A and collagen adhesin)
      as target in a DNA vaccine. Intranasal immunization with a pDNA mixture coding
      the four adhesins, triggered significant levels of specific serum and mucosal Ig
      that inhibited S. aureus adhesion to cow mammary gland epithelial cells in vitro.
      Splenocytes of immunized mice challenged in vitro with S. aureus extracts showed
      a strong proliferative response. Finally, immunized mice were significantly
      protected against intramammary challenge with S. aureus. Our data confirm the
      feasibility of a genetic mucosal vaccine targeting S. aureus adhesins and prompt
      further study to test the efficacy in preventing cow mastitis.

PMID- 16580098
TI  - The tick protective antigen, 4D8, is a conserved protein involved in modulation
      of tick blood ingestion and reproduction.
AB  - The gene that encodes the tick protective antigen, 4D8, was cloned from 10
      species belonging to 6 genera, and the nucleotide and amino acid sequences were
      analyzed. 4D8 nucleotide and protein sequences were conserved among these tick
      species with identity/similarity between 65-98 and 60-98%, respectively. The
      function of 4D8 was characterized by RNA interference (RNAi) in five tick
      species. After the ticks were allowed to feed, degeneration of gut, salivary
      glands and reproductive tissues was observed, and tick survival, weight and
      oviposition were significantly reduced. 4D8 RNAi effected >90% reduction in
      oviposition in all tick species tested. Because of the critical role that 4D8
      plays during tick feeding and oviposition, which ultimately results in the
      reduction of tick progeny, we proposed the generic name "subolesin" (Latin,
      suboles: offspring, progeny) for tick 4D8 proteins and subA for the subolesin
      encoding gene.

PMID- 16580099
TI  - Protective effect of vaccination with recombinant proteins from Streptococcus
      equi subspecies equi in a strangles model in the mouse.
AB  - A mouse model resembling Streptococcus equi subspecies equi infection in the
      horse, strangles, was used to assess the protective effect of vaccination with
      selected recombinant proteins from S. equi subsp. equi. After challenge the
      infection was monitored by weight loss and by nasal colonisation with S. equi
      subsp. equi. Vaccination with a collagen-binding protein (CNE) and a collagen
      like protein (SclC) resulted in protective antibodies, whereas a novel
      fibronectin-binding protein (FNEB) did not. Co-administration of CNE with EAG, a
      poorly immunogenic alpha2-macroglobulin-, albumin- and immunoglobulin G-binding
      protein, resulted in a significant synergistic effect and enhanced the protective
      immune response against EAG.

PMID- 16580100
TI  - Re: the use of a fine-gauge needle reduces pain in open carpal tunnel
      decompression: a randomized controlled trial. Watts AC, McEachan J (2005).
      Journal of Hand Surgery, 30B: 6: 615-617.

PMID- 16580101
TI  - The innervation of the medial humeral epicondyle: implications for medial
      epicondylar pain.
AB  - The purpose of this study was identification of the innervation of the medial
      humeral epicondyle which has not been described before. In 20 patients, the
      medial intermuscular septum was evaluated histopathologically: the nerve was
      identified in 15 specimens without S-100 staining, and in the remaining 5 with S
      100 staining. In six fresh cadavers, bilateral dissections identified the source
      of this nerve as the radial nerve in the axilla, coursing adjacent to the ulnar
      nerve in the upper arm, then moving laterally to be superficial to, or within,
      the medial intermuscular septum, until the nerve terminated in the periosteum of
      the medial humeral epicondyle, at the origin of the flexor-pronator muscle mass.
      In one specimen, a branch from the ulnar nerve in the axilla contributed to this
      nerve to the medial humeral epicondyle.

PMID- 16580103
TI  - Re: the use of a fine-gauge needle reduces pain in open carpal tunnel
      decompression: a randomized controlled trial. Watts AC, McEachan J (2005).
      Journal of Hand Surgery, 30B: 6: 615-617.

PMID- 16580104
TI  - Closed rupture of the flexor tendons of the little finger secondary to non-union
      of fractures of the hook of the hamate.
AB  - We report six patients with closed flexor tendon rupture affecting the little
      finger, occurring secondarily to non-union of the hook of the hamate bone. The
      ununited fragments were separated from the basal part of the hook by more than
      1mm. The fragments were also rounded and showed marginal sclerosis. Non-union was
      located in the middle part of the hook in three patients, the tip in two, and the
      base in one. At operation, the fragments were removed in all patients. Five
      patients were treated by free tendon grafts using three palmaris and two
      plantaris grafts and one underwent tendon transfer. Postoperative total range of
      active motion of the little finger averaged 218 degrees (range 185-265 degrees ).
      All patients returned to their original employment. This series would suggest
      that flexor tendon rupture can occur after fracture of the hook of the hamate
      bone, even when the ununited fragment is small and/or rounded.

PMID- 16580105
TI  - Remediation of cadmium contamination in paddy soils by washing with chemicals:
      selection of washing chemicals.
AB  - The efficiencies of neutral salts, strong acids, and chelates were tested for
      extracting cadmium (Cd) from three paddy soils. The higher the selectivity of the
      cations of the added neutral salts toward soil adsorption sites, the lower the pH
      in the extracts and the more soil Cd could be extracted. In addition, soil carbon
      and nitrogen contents and mineral composition were closely associated with the
      amount of Cd extracted. Calcium chloride and iron(III) chloride were selected as
      wash chemicals to restore Cd-contaminated paddy soils in situ. Washing with
      calcium chloride led to the formation of Cd chloride complexes, enhancing Cd
      extraction from the soils. The washing also substantially decreased soil levels
      of exchangeable and acid-soluble Cd, which are the major forms of bioavailable Cd
      for rice (Oryza sativa L.). The optimum conditions for in situ soil washing were
      also determined for calcium chloride.

PMID- 16580106
TI  - Migration and maternal health services utilization in rural Guatemala.
AB  - This article examines the relationship between migration and the use of formal
      maternal health-care services among rural women in Guatemala. We identify
      assimilation, diffusion, and remittances as three potential pathways through
      which migration can affect health-care service utilization in rural areas. Using
      data from the 1995 Guatemalan Survey of Family Health and multi-level regression
      models, we estimate the impact of migration experience at the individual,
      household, and community level on the use of formal prenatal care and delivery
      assistance. We find that urban migration experience and having relatives abroad
      are associated with a greater likelihood of formal prenatal care utilization,
      after taking account of background characteristics and enabling resources.
      Migration experience at all levels is also strongly associated with formal
      delivery assistance; however, this association operates primarily through the
      positive association between migration and enabling resources. The differential
      effects of out-migration on maternal health-care service utilization reflect the
      different barriers to service use that exist for formal prenatal care and
      delivery assistance. Financial cost and geographic access are the most important
      barriers to formal delivery assistance, whereas awareness and acceptance remain
      as important barriers to the use of formal prenatal care in rural Guatemala.
      Urban migration experience and social ties to urban and international migrants
      lower the barriers to formal maternal health-care utilization through the
      acquisition and diffusion of new ideas and practices, and the return flow of
      financial resources.

PMID- 16580107
TI  - The association of subjective social status and health in low-income Mexican
      origin individuals in Texas.
AB  - There is only limited research on subjective social status (SSS) and its effect
      on health in general and in minority US populations in particular. This study
      first investigates the determinants of SSS and the relationship between SSS and
      objective social status. It then explores the relationships of SSS to self
      reported physical health, self-reported mental health, and self-rated health
      (SRH). The study population consists of Mexican-origin individuals living in low
      income neighborhoods in Texas and grouped into acculturation categories based on
      nativity and use of the Spanish language. We also investigate the role of
      reference groups. Results indicate that there is no disjuncture between
      subjective and objective status in this population but that the less acculturated
      groups rank their social status based on different criteria than the more
      acculturated. People compare themselves mainly with those similar to them and
      average subjective status in the different acculturation groups accurately
      reflects the objective status of the group. Sociocultural factors, in particular
      perceived differences in opportunities, explain differences between subjective
      and objective status. Subjective status was associated with all health outcomes.
      When controlling for objective status, subjective status was associated with
      mental health and SRH but not with physical health. Objective status indicators
      were consistently associated with all health outcomes, indicating the prominence
      of objective socioeconomic status in affecting health in this low-income minority
      population. Sociocultural characteristics appear to mediate the effect of SSS on
      health. In particular, perceived victimization might mediate the effect of SSS on
      mental health.

PMID- 16580108
TI  - The relationship between nonstandard working and mental health in a
      representative sample of the South Korean population.
AB  - In light of escalating job insecurity due to increasing numbers of nonstandard
      workers, this study examined the association between nonstandard employment and
      mental health among South Korean workers. We analyzed a representative weighted
      sample of 2086 men and 1194 women aged 20-64 years, using data from the 1998
      Korean National Health and Nutrition Examination Survey. Nonstandard employment
      included part-time work, temporary work, and daily work. Mental health was
      measured with indicators of self-reported depression and suicidal ideation. Based
      on age-adjusted prevalence of mental health, nonstandard employees were more
      likely to be mentally ill compared to standard employees. Furthermore,
      nonstandard work status was associated with poor mental health after adjusting
      for socioeconomic position (education, occupational class, and income) and health
      behaviors (smoking, alcohol consumption, and exercise). However, the pattern of
      the relationship between nonstandard work and mental health differed by gender.
      Female gender was significantly associated with poor mental health. Although
      males tended to report more suicidal ideation, this difference was not
      statistically significant. Considering the increasing prevalence of nonstandard
      working conditions in South Korea, the results call for more longitudinal
      research on the mental health effects of nonstandard work.

PMID- 16580109
TI  - Clinicians and the governance of hospitals: a cross-cultural perspective on
      relations between profession and management.
AB  - This paper explores similarities and differences in the value stances of
      clinicians and hospital managers in Australia, England, New Zealand and China,
      and provides some new insights into how we theorise about the health profession
      and its relations with management. The paper draws on data derived from a closed
      ended questionnaire administered to 2637 hospital-based medical, nursing and
      managerial staff. We examine variations between the countries in the value
      orientations of doctors, nurses and managers by considering their assessments of
      issues that are the focus of reform. In particular, we examine the ways in which
      the Chinese findings differ from those of the other countries. Whereas the
      results from the Commonwealth hospitals showed a marked division between
      clinicians and managers about issues that can affect clinical autonomy, this was
      not the case in the Chinese hospitals. The concluding discussion traces these
      differences to a number of cultural, organisational and policy-based factors. The
      implications of our findings on how we conceive the relationship between
      professionals and organisations are then discussed, as are further lines of
      research.

PMID- 16580110
TI  - Risperidone in the treatment of psychotic depression.
AB  - In the preset study, the authors investigated that effects of the antipsychotic
      drug risperidone on psychotic depression and examined the mechanism of
      risperidone to ameliorate psychotic depression. Fifteen patients met the DSM-IV
      criteria for major depressive disorder with psychotic features and the remaining
      five patients met those for bipolar I disorder (most recent episode depressed)
      with psychotic features (M/F: 8/12, age: 54+/-18). All patients were evaluated
      regarding their clinical improvement using the Hamilton Rating Scale for
      Depression (Ham-D), and Positive and Negative Syndrome Scale (PANSS). In
      addition, plasma concentrations of HVA and MHPG were analyzed by HPLC. Patients
      with a 50% or more improvement in Ham-D score were defined as responders. Three
      were prescribed risperidone alone, and the other 17 were administered risperidone
      as an addition to preexisting antidepressants or mood stabilizers. The
      preexisting antidepressants or mood stabilizers were as follows: paroxetine (6),
      lithium (3), valproic acid (3), clomipramine (2), fluvoxamine (1), amitriptyline
      (1), amoxapine (1). The average dose of risperidone was 1.8+/-0.5 mg/day. Eleven
      of twenty patients (55%) turned out to be responders 4 weeks after initiation of
      risperidone administration. No differences were observed between responders and
      nonresponders with respect to age, sex, Ham-D score before risperidone treatment,
      dose and plasma level of risperidone or its active metabolite, 9
      hydroxyrisperidone. Plasma HVA levels before risperidone administration in
      responders were significantly higher than those in nonresponders. In addition, a
      significant correlation was observed between changes in plasma HVA level and the
      percentage improvement on Ham-D score. These results indicate that treatment with
      risperidone is effective to ameliorate psychotic depression, and the influence of
      risperidone on dopaminergic activity is associated with its efficacy.

PMID- 16580111
TI  - Evolutionary theory, psychiatry, and psychopharmacology.
AB  - Darwin's seminal publications in the nineteenth century laid the foundation for
      an evolutionary approach to psychology and psychiatry. Advances in 20th century
      evolutionary theory facilitated the development of evolutionary psychology and
      psychiatry as recognized areas of scientific investigation. In this century,
      advances in understanding the molecular basis of evolution, of the mind, and of
      psychopathology, offer the possibility of an integrated approach to understanding
      the proximal (psychobiological) and distal (evolutionary) mechanisms of interest
      to psychiatry and psychopharmacology. There is, for example, growing interest in
      the question of whether specific genetic variants mediate psychobiological
      processes that have evolutionary value in specific contexts, and of the
      implications of this for understanding the vulnerability to psychopathology and
      for considering the advantages and limitations of pharmacotherapy. The
      evolutionary value, and gene-environmental mediation, of early life programming
      is potentially a particularly rich area of investigation. Although evolutionary
      approaches to psychology and to medicine face important conceptual and
      methodological challenges, current work is increasingly sophisticated, and may
      prove to be an important foundational discipline for clinicians and researchers
      in psychiatry and psychopharmacology.

PMID- 16580112
TI  - Correspondence Re: "C. Guo, K.E. McMartin, The cytotoxicity of oxalate,
      metabolite of ethylene glycol, is due to calcium oxalate monohydrate formation,
      Toxicology 208 (3) (2005) 347-355".

PMID- 16580113
TI  - Liver initiation activity of norfloxacin but not nalidixic acid, pipemidic acid,
      and ciprofloxacin on in vivo short-term liver initiation assay in rats.
AB  - This study aimed to examine the in vivo initiation activity of the quinolone
      antimicrobials--nalidixic acid (NA), pipemidic acid (PPA), ciprofloxacin (CPFX),
      and norfloxacin (NFLX)--by using an in vivo short-term liver initiation assay.
      Rats were subjected to a two-thirds partial hepatectomy on day 0 and 12 h after
      completion of this procedure were treated once orally with each quinolone or
      vehicle. Subsequently, they were fed a basal diet for 14 days and a diet
      containing 0.015% of 2-acetylaminofluorene for the following 10 days. On day 19,
      a single oral dose of carbon tetrachloride at 0.8 mL/kg body weight was
      administered. On day 34, they were sacrificed under ether anesthesia, and liver
      slices were fixed in 10% neutral buffered formalin for immunohistochemical
      examination of glutathione S-transferase placental form (GST-P) positive foci.
      Administration of NFLX resulted in a significant increase in the mean number and
      area of GST-P positive foci; however, administration of the three other
      quinolones did not produce any increase. These results suggest that only NFLX has
      an initiation activity in rats under the conditions used in the present study.

PMID- 16580115
TI  - Effect of relining, water storage and cyclic loading on the flexural strength of
      a denture base acrylic resin.
AB  - OBJECTIVES: This study investigated the effect of relining, water storage and
      cyclic loading on the ultimate flexural strength (FS(U)) and on the flexural
      strength at the proportional limit (FS(Pl)) of a denture base acrylic resin
      (Lucitone 550-L). METHODS: Rectangular bars of L were made (64 mm x 10 mm x 2 mm)
      and relined (1.3mm) with four relining resins (Kooliner-K, Ufi Gel Hard-UGH,
      Tokuso Rebase Fast-TR and New Truliner-NT). In addition, specimens relined with L
      and intact L specimens were made (64 mm x 10 mm x 3.3 mm). A three-point flexural
      test was applied on the specimens (n=10) after (1) polymerization; (2) water
      storage (30 days); (3) cyclic loading (10,000 cycles at 5 Hz) and (4) water
      storage (30 days)+cyclic loading. Data (MPa) were analyzed with three-way ANOVA
      and Tukey's HSD tests (alpha=0.05). To test for a possible correlation between
      FS(U) and FS(Pl), a linear regression coefficient "r" was calculated. RESULTS:
      After water storage, L-UGH and L-TR demonstrated an increased FS(U) (41.49-50.64
      MPa and 49.95-57.36 MPa, respectively) (P<0.05). Only L-TR demonstrated an
      increased FS(Pl) (20.58-24.21 MPa) after water storage (P<0.05). L-L had the
      highest FS(U) (between 78.57 and 85.09 MPa) and FS(Pl) (between 31.30 and 34.17
      MPa) (P<0.05). The cyclic loading decreased the FS(U) and FS(Pl) of all materials
      (P<0.05). Regression analysis showed a strong linear correlation between the two
      variables (r=0.941). CONCLUSIONS: Water storage improved the FS(U) of L-UGH and L
      TR and the FS(Pl) of L-TR. L-L produced the highest FS(U) and FS(Pl). The FS(U)
      and FS(Pl) of all materials were detrimentally influenced by cyclic loading.

PMID- 16580114
TI  - Fiber-reinforced packable resin composites in Class II cavities.
AB  - OBJECTIVE: To evaluate the 6-year performance of two glass fiber-reinforced
      packable resin composites in Class II cavities. METHODS: Sixty-three participants
      received 87 medium to large, cervically dentin bordered, Class II restorations of
      two fiber-reinforced resin composites, 42 Nulite F (N) and 45 Alert (A). The
      restorations were evaluated clinically, according to slightly modified USPHS
      criteria at baseline, after 6 months, and yearly during 6 years. RESULTS: At 2
      years the cumulative failure frequencies for N and A were 4.8% and 2.2%,
      respectively, which increased at 6 years to 25.0% and 12.8%. Reasons for failure
      were secondary caries, material and cusp fracture. The majority of the failures
      occurred after 3 years. Secondary caries occurred between 4 and 6 years. The
      incorporation of fibers resulted in very rough surface characteristics.
      CONCLUSIONS: A rather high failure rate was observed for one of the fiber
      reinforced resin composites, while the other fulfilled the ADA criteria. The
      occurrence of most failures after 3 years indicated the necessity of long-term
      evaluations of new materials.

PMID- 16580117
TI  - Peripartum hysterectomy in a teaching hospital in the eastern region of Turkey.

PMID- 16580116
TI  - Mechanism of cytosol phospholipase C and sphingomyelinase-induced lysosome
      destabilization.
AB  - Lysosomal disintegration may cause apoptosis, necrosis and some diseases.
      However, mechanisms for these events are still unclear. In this study, we
      measured lysosomal beta-hexosaminidase free activity, membrane potential and
      intralysosomal pH. The results revealed that the cytosolic extracts of rat
      hepatocytes could increase the lysosomal permeability to both potassium ions and
      protons, and osmotically destabilize lysosomes via K(+)/H(+) exchange. The
      effects of cytosol on lysosomes could be completely abolished by D609, which
      inhibited both phospholipase C and sphingomyelinase, and partly prevented by
      sphingomyelinase inhibitor Ara-AMP, but not by the inhibitors of PLA(2).
      Moreover, purified phospholipase C could destabilize the lysosomes while
      phospholipase A(2) and phospholipase D did not produce such effects. The
      cytosolic phospholipases hydrolyzed lysosomal membrane phospholipids by 50%,
      which could be prevented by D609. Disintegration of the cytosol-treated lysosomes
      biphasically depended on the cytosolic [Ca(2+)]. The cytosol did not disintegrate
      lysosomes below 100 nM or above 10 muM cytosolic [Ca(2+)], but markedly
      destabilized lysosomes at about 340 nM [Ca(2+)]. The results suggest that
      cytosolic phospholipase C and sphingomyelinase may be responsible for the
      alterations in lysosomal stability by increasing the ion permeability.

PMID- 16580118
TI  - Adiponectin and glucose levels in women with negative or false positive glucose
      challenge test.
AB  - OBJECTIVE: To determine whether there is a correlation between adiponectin levels
      and glucose levels in women screened for gestational diabetes mellitus by means
      of a 50-g oral glucose challenge test, and to examine the difference in
      adiponectin levels between women who tested negative, and those who tested false
      positive. We further calculated the correlations between adiponectin levels and
      glucose levels, body mass index, gestational age and maternal age. METHODS: A
      case control study included 171 mothers with negative or false positive results
      in the 1-h 50-g glucose challenge test at 24-28 gestational weeks. Serum
      adiponectin levels were determined by radioimmunoassay at the time of the glucose
      challenge test. RESULTS: There was a significant difference between women who
      tested negative at screening, and those who tested false positive with respect to
      age, prepregnancy body weight and body mass index, and adiponectin levels.
      Correlation analysis showed adiponectin levels to be negatively correlated to
      glucose levels (r=-0.193, P=0.011). To examine the association between glucose
      levels, adiponectin levels and demographic variables, multiple linear regression
      analysis was carried out. Prepregnancy body mass index and age accounted for
      14.6% of the variance in the glucose challenge test. Adiponectin levels did not
      contribute independently to the variation in glucose levels. A further multiple
      linear regression analysis was undertaken to investigate the association between
      adiponectin levels and age, prepregnancy body mass index and glucose levels in
      the glucose challenge test. In this regression model, prepregnancy body mass
      index and age explained 12.1% of the variance in adiponectin levels. CONCLUSIONS:
      In conclusion, our study indicated a negative correlation between adiponectin and
      glucose levels in women screened for gestational diabetes mellitus by a glucose
      challenge test. We further found that maternal age and body mass index were
      independent risk factors for a false positive glucose challenge test. Reduced
      adiponectin levels in women who tested false positive on the glucose challenge
      test were dependent on advanced age and higher body mass index.

PMID- 16580119
TI  - Pharmacological doses of the natural phyto-SERM DT56a (Femarelle) have no effect
      on MCF-7 human breast cancer cell-line.

PMID- 16580120
TI  - Sorption of cadmium and zinc from aqueous solutions by zeolite 4A, zeolite 13X
      and bentonite.
AB  - The sorption and desorption of cadmium and zinc on zeolite 4A, zeolite 13X and
      bentonite has been studied using batch sorption studies. Parameters such as
      equilibrium time, effect of pH and sorbent dose were studied. The sorbents
      exhibited good sorption potential for cadmium and zinc with a peak value at pH
      6.0 and 6.5, respectively. The sorption followed the Freundlich sorption model.
      More than 70% sorption occurred within 20 min and equilibrium was attained at
      around 90 min for the three sorbents. The metals sorption by zeolite 4A was
      higher than that by zeolite 13X and bentonite. The desorption studies were
      carried out using NaCl solution and the effect of NaCl concentration on
      desorption was also studied. Maximum desorption of 76% for cadmium and 80% for
      zinc occurred with 10% NaCl.

PMID- 16580121
TI  - Application and sensitivity testing of a eutrophication assessment method on
      coastal systems in the United States and European Union.
AB  - The Assessment of Estuarine Trophic Status (ASSETS) screening model has been
      extended to allow its application to both estuarine and coastal systems. The
      model, which combines elements of pressure, state and response, was tested on
      four systems: Maryland Coastal Bays and Long Island Sound in the United States
      and The Firth of Clyde (Scotland) and Tagus Estuary (Portugal) in the European
      Union. The overall scores were: Maryland Coastal Bays: Bad; Firth of Clyde: Poor;
      Tagus Estuary: Good. Long Island Sound was modelled along a timeline, using 1991
      data (score: Bad) and 2002 data (score: Moderate). The improvement registered for
      Long Island Sound is a consequence of the reduction in nutrient loading, and the
      ASSETS score changed accordingly. The two main areas where developments are
      needed are (a) In the definition of type-specific ranges for eutrophication
      parameters, due to the recognition that natural or pristine conditions may vary
      widely, and the use of a uniform set of thresholds artificially penalizes some
      systems and potentially leads to misclassification; (b) In the definition and
      quantification of measures which will result in an improved state through a
      change in pressures, as well as in the definition of appropriate metrics through
      which response may be assessed. One possibility is the use of detailed research
      models where different response scenarios potentially produce changes in pressure
      and state. These outputs may be used to drive screening models and analyze the
      suitability of candidate metrics for evaluating management options.

PMID- 16580122
TI  - The effect of urban quality improvements on economic activity.
AB  - This paper is concerned with the link between urban quality improvements and
      economic activity. A key question is whether improvements in the urban
      environment which might be achieved, for instance, through pedestrianisation,
      will affect business location choices--for example, are office or retail
      businesses particularly keen to locate in more pleasant urban places? The paper
      outlines the current state of development of the literature with respect to the
      influence of urban quality on economic activity, and proposes a framework for
      forecasting economic impacts based on three communities of reference: customers,
      employees, and the businesses themselves. The results from original modelling of
      a case study area in Manchester, England are reported and suggest that the
      positive uplifts that may be expected from environmental improvement programmes
      may well be on a scale which is significant. The research is obviously important
      for the urban regeneration and renaissance agendas which posit attractive and
      well-designed environments as a way to create the right conditions for promoting
      economic growth.

PMID- 16580123
TI  - The effects of leachate recirculation with supplemental water addition on methane
      production and waste decomposition in a simulated tropical landfill.
AB  - In order to increase methane production efficiency, leachate recirculation is
      applied in landfills to increase moisture content and circulate organic matter
      back into the landfill cell. In the case of tropical landfills, where high
      temperature and evaporation occurs, leachate recirculation may not be enough to
      maintain the moisture content, therefore supplemental water addition into the
      cell is an option that could help stabilize moisture levels as well as stimulate
      biological activity. The objectives of this study were to determine the effects
      of leachate recirculation and supplemental water addition on municipal solid
      waste decomposition and methane production in three anaerobic digestion reactors.
      Anaerobic digestion with leachate recirculation and supplemental water addition
      showed the highest performance in terms of cumulative methane production and the
      stabilization period time required. It produced an accumulated methane production
      of 54.87 l/kg dry weight of MSW at an average rate of 0.58 l/kg dry weight/d and
      reached the stabilization phase on day 180. The leachate recirculation reactor
      provided 17.04 l/kg dry weight at a rate of 0.14l/kg dry weight/d and reached the
      stabilization phase on day 290. The control reactor provided 9.02 l/kg dry weight
      at a rate of 0.10 l/kg dry weight/d, and reached the stabilization phase on day
      270. Increasing the organic loading rate (OLR) after the waste had reached the
      stabilization phase made it possible to increase the methane content of the gas,
      the methane production rate, and the COD removal. Comparison of the reactors'
      efficiencies at maximum OLR (5 kgCOD/m(3)/d) in terms of the methane production
      rate showed that the reactor using leachate recirculation with supplemental water
      addition still gave the highest performance (1.56 l/kg dry weight/d), whereas the
      leachate recirculation reactor and the control reactor provided 0.69 l/kg dry
      weight/d and 0.43 l/kg dry weight/d, respectively. However, when considering
      methane composition (average 63.09%) and COD removal (average 90.60%), slight
      differences were found among these three reactors.

PMID- 16580124
TI  - Aggregating high-priority landscape areas to the parcel level: an easement
      implementation tool.
AB  - Landscape characteristics and parcel ownership information are often collected on
      different spatial scales leading to difficulties in implementing land use plans
      at the parcel level. This study provides a method for aggregating highly resolute
      landscape planning information to the parcel level. Our parcel prioritization
      model directly incorporates a Land Trust's conservation goals in the form of a
      compromise programming model. We then demonstrate the use of our approach for
      implementation decisions, including parcel selection under a budget constraint
      and the estimation of a total conservation budget necessary to meet specific
      conservation goals. We found that these cost constraints significantly alter the
      composition of the 'best' parcels for conservation and can also provide guidance
      for implementation. The model's results were integral to a local Land Trust's
      ability to further define and achieve their goals.

PMID- 16580125
TI  - Comparison of vegetation conditions along two backcountry trails in Mount Robson
      Provincial Park, British Columbia (Canada).
AB  - Vegetation conditions, i.e., plant cover, species richness, and the presence of
      exotic species, are compared along a high-use trail (Berg Lake Trail--BLT) and a
      low use trail (Mt. Fitzwilliam Trail--FWT) in Canada's Mt. Robson Provincial
      Park. We established 71 paired quadrats (1 m x 1 m), and assessed the amount of
      vegetation cover and species richness by four main lifeforms, i.e., woody
      species, herbaceous species, ferns, and moss, lichen and fungi. The following
      hypotheses were tested: (1) differences exist between control and trailside
      quadrats in vegetation cover, species richness and floristic diversity, and (2)
      differences exist between the high and low-use trails in the above-mentioned
      three parameters. Results show that for the majority of variables the differences
      between the control and trailside quadrats are statistically not significant.
      Variables showing significant differences are relative vegetation cover (for BLT
      only), exposed soil (BLT and FWT), herbaceous cover (FWT), moss, lichen and fungi
      cover (BLT), overall species richness (BLT), and herbaceous species richness
      (BLT). Ruderal and exotic species are present but only on trailside quadrats of
      the high-use trail. Results indicate that the Park administration's strategy to
      disperse use in the Mt. Robson Provincial Park should be examined critically, and
      some guidelines for acceptability of changes should be developed.

PMID- 16580126
TI  - Evaluation of municipal wastewater treatment plants with different technologies
      at Las Rozas, Madrid (Spain).
AB  - Eight small-scale municipal wastewater treatment plants were evaluated over a
      period of 19 months in the suburb of Las Rozas in Madrid (Spain). Four plants
      used compact extended aeration, two used conventional activated sludge, two used
      conventional extended aeration, one used a rotary biodisc reactor and the other
      used a peat bed reactor. The best results were obtained from the plants that used
      conventional technologies and the biodisc. Conventional activated sludge and
      extended aeration had higher removal efficiencies for ammonia, TSS, COD and
      BOD(5) and produced good quality final effluents for final disposal in accordance
      with the discharge standard. Empirical equations that correlated the
      concentration of dissolved oxygen in the effluents with the efficiencies of TSS,
      ammonia, COD and BOD(5) removals for all plants evaluated were obtained. The
      performance of the plants using compact extended aeration was affected more than
      those using conventional technologies or rotary biodisc when the capacity
      exceeded that of its initial design.

PMID- 16580127
TI  - Is love of nature in the US becoming love of electronic media? 16-year downtrend
      in national park visits explained by watching movies, playing video games,
      internet use, and oil prices.
AB  - After 50 years of steady increase, per capita visits to US national parks have
      declined since 1988. This decline, coincident with the rise in electronic
      entertainment media, may represent a shift in recreation choices with broader
      implications for the value placed on biodiversity conservation and
      environmentally responsible behavior. We compared the decline in per capita
      visits with a set of indicators representing alternate recreation choices and
      constraints. The Spearman correlation analyses found this decline in NPV to be
      significantly negatively correlated with several electronic entertainment
      indicators: hours of television, (rs=-0.743, P<0.001), video games (rs=-0.773,
      P<0.001), home movies (rs=-0.788, P<0.001), theatre attendance (rs=-0.587,
      P<0.025) and internet use (rs=-0.783, P<0.001). There were also significant
      negative correlations with oil prices (rs=-0.547, P<0.025), foreign travel (rs=
      0.452, P<0.05), and Appalachian Trail hikers (rs=-0.785, P<0.001). Income was
      significantly positively correlated with foreign travel (rs=0.621, P<0.005) but
      negatively correlated with national park visits (rs=-0.697, P<0.005). There was
      no significant correlation of mean number of vacation days, indicating available
      vacation time is probably not a factor. Federal funding actually increased during
      this period, and so was rejected as a probable factor. Park capacity was rejected
      as limiting since both total overnight stays and visits at the seven most popular
      parks rose well into the mid-1990s. Aging of baby boomers was also rejected as
      they are only now reaching retirement age, and thus during the period of
      visitation decline were still of prime family vacation age. Multiple linear
      regression of four of the entertainment media variables as well as oil prices
      explains 97.5% of this recent decline (r=0.975, multiple r2=0.950, adjusted
      multiple r2=0.925, SE=0.015, F=37.800, P<0.0001). We may be seeing evidence of a
      fundamental shift away from people's appreciation of nature (biophilia, Wilson
      1984) to 'videophilia,' which we here define as "the new human tendency to focus
      on sedentary activities involving electronic media." Such a shift would not bode
      well for the future of biodiversity conservation.

PMID- 16580128
TI  - Environmental performance policy indicators for the public sector: the case of
      the defence sector.
AB  - The development of environmental performance policy indicators for public
      services, and in particular for the defence sector, is an emerging issue. Despite
      a number of recent initiatives there has been little work done in this area,
      since the other sectors usually focused on are agriculture, transport, industry,
      tourism and energy. This type of tool can be an important component for
      environmental performance evaluation at policy level, when integrated in the
      general performance assessment system of public missions and activities. The main
      objective of this research was to develop environmental performance policy
      indicators for the public sector, specifically applied to the defence sector.
      Previous research included an assessment of the environmental profile, through
      the evaluation of how environmental management practices have been adopted in
      this sector and an assessment of environmental aspects and impacts. This paper
      builds upon that previous research, developing an indicator framework--SEPI-
      supported by the selection and construction of environmental performance
      indicators. Another aim is to discuss how the current environmental indicator
      framework can be integrated into overall performance management. The Portuguese
      defence sector is presented and the usefulness of this methodology demonstrated.
      Feasibility and relevancy criteria are applied to evaluate the set of indicators
      proposed, allowing indicators to be scored and indicators for the policy level to
      be obtained.

PMID- 16580129
TI  - Hormonal regulation of PKC: estrogen up-regulates PKCeta expression in estrogen
      responsive breast cancer cells.
AB  - Protein kinase C (PKC) is involved in several major signal transduction pathways
      that control gene expression cell growth and differentiation. The PKCeta isoform
      appears as a candidate regulator of mammary gland proliferation or
      differentiation, as its expression is up-regulated in the mammary gland in the
      transit from resting to the pregnant state. The purpose of this study was to
      examine the hormonal regulation of PKCeta. Here we show that estradiol
      specifically up-regulates the expression of PKCeta in the estrogen-responsive
      lines MCF-7 and T47D but not in the estrogen non-responsive line MDA-MB 231.
      Interestingly, the presence of progesterone, involved in the differentiation of
      the mammary gland, reduced the estrogen-induced PKCeta expression in a time
      dependent manner. Thus, our studies suggest that PKCeta has an important role in
      signalling pathways regulating mammary gland proliferation and its development.

PMID- 16580130
TI  - The long-term exposure of rat cultured dorsal root ganglion cells to bradykinin
      induced the release of prostaglandin E2 by the activation of cyclooxygenase-2.
AB  - The effects of long-term exposure of primary cultured rat dorsal root ganglion
      (DRG) cells to bradykinin (BK), compared to short-term exposure, were
      investigated to establish whether BK could induce prostaglandin E2 (PGE2) release
      from DRG cells. Short-term exposure (30 min) resulted in a small but significant
      amount of PGE2 release which was mainly inhibited by a selective COX-1 inhibitor,
      SC-560 but only partially by a selective COX-2 inhibitor, NS-398, and did not
      induce COX-2 protein as determined by Western blotting. In contrast, long-term
      exposure (3 h) induced a large amount of PGE2 release, which was completely
      abolished by indomethacin or NS-398. The level of COX-2 mRNA began to be detected
      by ribonuclease protection assay after 30 min of 100 nM BK exposure, maintained
      maximal expression for 1 h, and subsequently declined to the basal level. The
      level of COX-2 protein was expressed to follow the time course of COX-2 mRNA
      induction by BK in a delayed but similar kinetic manner. The expression of COX-2
      induced by BK in DRG cells was inhibited by a BK B2 receptor antagonist, HOE140,
      but not a B1 receptor antagonist, Lys-des-Arg9, (Leu8)-BK. Thus, BK has been
      shown to induce COX-2 protein by B2 receptor, which may cause prostanoid
      generation in rat DRG cells, which may play an important role in the pathogenesis
      of inflammatory pain and hyperalgesia around the primary sensory neurons.

PMID- 16580131
TI  - Differential suppression of endotoxin-inducible inflammatory cytokines by nuclear
      factor kappa B (NFkappaB) inhibitor in rat microglia.
AB  - The molecular mechanism by which the deleterious cytokines interleukin 1 beta (IL
      1beta) and tumor necrosis factor alpha (TNFalpha) are induced in endotoxin
      stimulated microglia was investigated from the viewpoint of signal transduction.
      Neither cytokine is produced in nonstimulated rat microglia, but both are
      remarkably induced by stimulation with endotoxin lipopolysaccharide (LPS). LPS
      inducible IL-1beta was significantly suppressed by pretreatment with the nuclear
      factor kappa B (NFkappaB) inhibitor ammonium pyrrolidine dithiocarbamate (APDC),
      but TNFalpha was not. APDC was actually confirmed to suppress the degradation of
      IkappaBalpha and IkappaBbeta in microglia, indicating a role for the inhibitor of
      NFkappaB activation. Taken together, these results suggest that the induction of
      IL-1beta and TNFalpha in endotoxin-stimulated microglia is differentially
      regulated at the level of NFkappaB activation.

PMID- 16580132
TI  - TAp73alpha induces tau phosphorylation in HEK293a cells via a transcription
      dependent mechanism.
AB  - p73 and tau both play roles in neurodevelopment and neurodegeneration. In this
      pilot study we show by Western blotting that TAp73alpha induces phosphorylation
      of human 2N4R tau at threonine-205 and at the PHF-1 epitope (serine366/serine404)
      in HEK293a cells. Neither the dominant negative isoform, DeltaNp73, nor a
      transcriptionally inactive mutant TAp73alpha(R292H) altered tau phosphorylation
      indicating that tau phosphorylation is dependent on the transcriptional activity
      of TAp73alpha. Consistent with this, confocal microscopy revealed that tau and
      TAp73alpha were spatially separated within the cell; tau being located in the
      cytoskeletal compartment whilst TAp73alpha was found in the nucleus. These
      findings have ramifications for microtubule dynamics associated with axonal
      growth during development and for neuronal death associated with Alzheimer's
      disease and other tauopathies.

PMID- 16580133
TI  - Acute photoreceptor degeneration down-regulates melanopsin expression in adult
      rat retina.
AB  - Melanopsin in retinal ganglion cells plays an important role in mammalian
      circadian systems. Previous studies indicate melanopsin is responsible for
      circadian photoentrainment independent of classical rods and cones. However,
      expression of melanopsin in ganglion cells may be regulated by photoreceptors. In
      this study, we investigated the effects of N-methyl-N-nitrosourea (MNU)-induced
      acute photoreceptor degeneration on melanopsin mRNA expression and protein
      distribution in adult rats. Expression of melanopsin was analyzed 0.5, 1, 5, 7,
      13 and 28 days after MNU administration by real-time RT-PCR and
      immunohistochemistry. MNU-induced gradual degeneration of photoreceptors, and by
      day 7 most of the photoreceptors were lost. The number of ganglion cells did not
      change significantly at all time points after MNU injection. In contrast,
      melanopsin mRNA decreased gradually with the loss of photoreceptors, at the same
      time pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA levels,
      which co-express with melanopsin in ganglion cells, were not affected by MNU
      treatment, indicating decrease of melanopsin mRNA levels is not due to ganglion
      cell damage. Distribution of melanopsin protein in the dendrites of ganglion
      cells dramatically decreased with the degeneration of photoreceptors, but its
      expression in the soma persisted for a long time. Our results suggest that intact
      photoreceptors maintain the expression of melanopsin and its distribution in
      ganglion cell dendrites.

PMID- 16580134
TI  - Fluorogold labeling of descending brain neurons in larval lamprey does not cause
      cell death.
AB  - In our previous double-labeling studies, the fluorescent anatomical tracers
      Fluorogold (FG) and Texas red dextran amine (TRDA) were used to demonstrate that
      descending brain neurons, approximately 80% of which are reticulospinal (RS)
      neurons, in spinal cord-transected larval lamprey regenerate their axons.
      However, the numbers of FG-labeled descending brain neurons decreased
      significantly with increasing recovery times, from 2 to 16 weeks. For some FG
      labeled mammalian neurons, FG appears to degrade and/or be lost over time, while
      in other neurons this tracer can kill neurons. In the present study, these
      possibilities were examined in larval lamprey for FG-labeled descending brain
      neurons. As in our previous studies, FG was applied to the spinal cord at 40%
      body length (BL, relative distance from the head) to retrogradely labeled
      descending brain neurons, and after recovery times of 2, 8, or 16 weeks, HRP, a
      non-toxic retrograde tracer, was applied to the spinal cord at 20% BL to
      determine if the numbers of HRP-labeled neurons were reduced. At these three
      recovery times, the numbers of HRP-labeled descending brain neurons were not
      significantly different than the numbers of HRP-labeled neurons in control
      animals that were not labeled with FG. Furthermore, the size and morphology of
      cell bodies and dendritic trees were not noticeably different in descending brain
      neurons with and without FG. Thus, in larval lamprey, FG does not appear to kill
      these neurons, but some FG probably is degraded and/or lost from neurons with
      increasing recovery times.

PMID- 16580135
TI  - Rhythmic post-transcriptional regulation of the circadian clock protein mPER2 in
      mammalian cells: a real-time analysis.
AB  - Post-transcriptional/translational mechanisms regulate the circadian clock system
      of many organisms, including mammals. The level of the essential clock protein
      mPER2 daily oscillates in peripheral cells as well as in neurons of the master
      oscillator in the suprachiasmatic nucleus (SCN). Post-translational modifications
      of mPER2, such as phosphorylation and ubiquitination, are likely involved in the
      regulation of its stability and intracellular accumulation rhythms, which in turn
      create an approximately 2-4 h delay from the rhythm of mPer2 mRNA. However, there
      are no direct evidences linking the above biochemical processes to the generation
      of the mPER2 protein cycle itself. Here, we show that multiple circadian waves of
      bioluminescence are detectable in cells constitutively expressing an mPer2
      luciferase fusion mRNA. This suggests that a post-transcriptional/translational
      mechanism itself is capable of generating the circadian mPER2 accumulation cycle,
      and thus this type of regulation may function in the circadian clock system in
      mammals.

PMID- 16580136
TI  - Comparison of different direct diagnostic methods to identify Babesia bovis and
      Babesia bigemina in animals vaccinated with live attenuated parasites.
AB  - Blood smear examination, flow cytometry, duplex Polymerase Chain Reaction (PCR),
      and duplex nested PCR (nPCR) were evaluated for detection of Babesia bigemina and
      Babesia bovis infections in cattle vaccinated with live attenuated strains. Two
      groups of four cattle were immunized with either B. bigemina (Bi) or B. bovis
      (Bo). On day 23 post inoculation (PI), Bi cattle were vaccinated with B. bovis
      (BiBo) and Bo cattle were vaccinated with B. bigemina (BoBi). Babesia bigemina
      was first detected by blood smear examination 7.5+/-3.5 days PI in the Bi group
      and 32.2+/-1.7 days PI in the BoBi group. The first occurrence of B. bovis in
      blood smears was 8.0 days PI in the Bo group and 36.0+/-2.6 days PI in the BiBo
      group. Flow cytometry detected parasitized erythrocytes on day 1.7+/-1.5 and
      2.2+/-1.5 PI in the Bi and Bo groups, respectively, but did not discriminate
      between the two Babesia spp. Duplex PCR detected B. bigemina on day 4.0+/-0.8 and
      26.0+/-0.8 PI in the Bi and BoBi groups, respectively, and B. bovis on day 4.0
      and 25.3+/-0.5 PI in the Bo and BiBo groups, respectively. The duplex nPCR
      detected B. bigemina on 3.0+/-0.8 and 25.0+/-0.0 days PI in the Bi and BoBi
      groups, respectively, and 4.7+/-1.7 and 27.7+/-6.2 days PI in the Bo and BiBo
      groups, respectively. Duplex nPCR outperformed the other tests in terms of
      specificity and sensitivity, indicating that it is the most useful method for
      identifying Babesia spp. in cattle following vaccination.

PMID- 16580137
TI  - Thyroid nodule: a potentially malignant lesion; optimal management from a
      surgical perspective.
AB  - Thyroid nodules are very common lesions, frequently detected by modern imaging
      methods (mainly ultrasonography). Despite that most thyroid nodules represent
      benign lesions, a small but significant percentage of them are malignant. Surgery
      is indicated when there is underlying malignancy (or suspicion for), pressure
      symptoms, or for cosmetic reasons. Total/near total thyroidectomy is the most
      radical procedure, which achieves cure, avoids the possibility of reoperation in
      the future (completion thyroidectomy), and facilitates postoperative management
      of the patient with underlying malignancy. Simple observation and thyroid hormone
      suppressive therapy are acceptable management options for patients with
      presumably benign thyroid nodules. Radioiodine therapy may be used for the
      management of patients with hyperfunctioning ("hot") thyroid nodules. Ablation of
      thyroid nodules (sclerosing therapy [alcohol injection] and laser
      photocoagulation) have been used for the in situ destruction of thyroid nodules;
      ablation therapy is currently viewed as experimental therapeutic method. Careful
      evaluation is required in order to avoid both overtreatment (mainly unnecessary
      surgery) as well as undertreatment of these potentially malignant, but highly
      curable lesions.

PMID- 16580138
TI  - Coupling energy metabolism with a mechanism to support brain-derived neurotrophic
      factor-mediated synaptic plasticity.
AB  - Synaptic plasticity and behaviors are likely dependent on the capacity of neurons
      to meet the energy demands imposed by neuronal activity. We used physical
      activity, a paradigm intrinsically associated with energy consumption/expenditure
      and cognitive enhancement, to study how energy metabolism interacts with the
      substrates for neuroplasticity. We found that in an area critical for learning
      and memory, the hippocampus, exercise modified aspects of energy metabolism by
      decreasing oxidative stress and increasing the levels of cytochrome c oxidase-II,
      a specific component of mitochondrial machinery. We infused 1,25-dihydroxyvitamin
      D3, a modulator of energy metabolism, directly into the hippocampus during 3 days
      of voluntary wheel running and measured its effects on brain-derived neurotrophic
      factor-mediated synaptic plasticity. Brain-derived neurotrophic factor is a
      central player for the effects of exercise on synaptic and cognitive plasticity.
      We found that 25-dihydroxyvitamin D3 decreased exercise-induced brain-derived
      neurotrophic factor but had no significant effect on neurotrophin-3 levels,
      thereby suggesting a level of specificity for brain-derived neurotrophic factor
      in the hippocampus. 25-Dihydroxyvitamin D3 injection also abolished the effects
      of exercise on the consummate end-products of brain-derived neurotrophic factor
      action, i.e. cyclic AMP response element-binding protein and synapsin I, and
      modulated phosphorylated calmodulin protein kinase II, a signal transduction
      cascade downstream to brain-derived neurotrophic factor action that is important
      for learning and memory. We also found that exercise significantly increased the
      expression of the mitochondrial uncoupling protein 2, an energy-balancing factor
      concerned with ATP production and free radical management. Our results reveal a
      fundamental mechanism by which key elements of energy metabolism may modulate the
      substrates of hippocampal synaptic plasticity.

PMID- 16580139
TI  - Transcription factor protein expression patterns by neural or neuronal progenitor
      cells of adult monkey subventricular zone.
AB  - The anterior subventricular zone of the adult mammalian brain contains progenitor
      cells which are upregulated after cerebral ischemia. We have previously reported
      that while a part of the progenitors residing in adult monkey anterior
      subventricular zone travels to the olfactory bulb, many of these cells sustain
      location in the anterior subventricular zone for months after injury, exhibiting
      a phenotype of either neural or neuronal precursors. Here we show that ischemia
      increased the numbers of anterior subventricular zone progenitor cells expressing
      developmentally regulated transcription factors including Pax6 (paired-box 6),
      Emx2 (empty spiracles-homeobox 2), Sox 1-3 (sex determining region Y-box 1-3),
      Ngn1 (neurogenin 1), Dlx1,5 (distalless-homeobox 1,5), Olig1,3 (oligodendrocyte
      lineage gene 1,3) and Nkx2.2 (Nk-box 2.2), as compared with control brains.
      Analysis of transcription factor protein expression by sustained neural or
      neuronal precursors in anterior subventricular zone revealed that these two cell
      types were positive for characteristic sets of transcription factors. The
      proteins Pax6, Emx2, Sox2,3 and Olig1 were predominantly localized to dividing
      neural precursors while the factors Sox1, Ngn1, Dlx1,5, Olig2 and Nkx2.2 were
      mainly expressed by neuronal precursors. Further, differences between monkeys and
      non-primate mammals emerged, related to expression patterns of Pax6, Olig2 and
      Dlx2. Our results suggest that a complex network of developmental signals might
      be involved in the specification of primate progenitor cells.

PMID- 16580140
TI  - Membrane excitability and fear conditioning in cerebellar Purkinje cell.
AB  - In a previous study it has been demonstrated that fear conditioning is associated
      with a long-lasting potentiation of parallel fiber to Purkinje cell synaptic
      transmission in vermal lobules V and VI. Since modifications of intrinsic
      membrane properties have been suggested to mediate some forms of memory
      processes, we investigated possible changes of Purkinje cell intrinsic properties
      following the same learning paradigm and in the same cerebellar region. By means
      of the patch clamp technique, Purkinje cell passive and active membrane
      properties were evaluated in slices prepared from rats 10 min or 24 h after fear
      conditioning and in slices from control naive animals. None of the evaluated
      parameters (input resistance, inward rectification, maximal firing frequency and
      the first inter-spike interval, post-burst afterhyperpolarization, action
      potential threshold and amplitude, action potential afterhyperpolarization) was
      significantly different between the three studied groups also in those cells
      where parallel fiber-Purkinje cell synapse was potentiated. Our results show that
      fear learning does not affect the intrinsic membrane properties involved in
      Purkinje cell firing. Therefore, at the level of Purkinje cell the plastic change
      associated with fear conditioning is specifically restricted to synaptic
      efficacy.

PMID- 16580141
TI  - Cell swelling, seizures and spreading depression: an impedance study.
AB  - The cellular processes that take place during the transition from pre-seizure
      state to seizure remain to be defined. In this study in awake, paralyzed rats, we
      used an electrical impedance measure of changes in extra-cellular intracranial
      volume to estimate changes in cell size in acute models of epilepsy. Animals were
      prepared with extradural electroencephalographic (EEG)/impedance electrodes and a
      venous catheter. On a subsequent day, animals were paralyzed, ventilated and
      treated with picrotoxin, kainic acid or fluorocitrate in doses that usually
      induce epileptiform discharges. We now report that increases in baseline
      impedance were induced by kainic acid and smaller increases by picrotoxin. We
      also demonstrated that epileptiform discharges were preceded by small,
      accelerated increases in impedance. Increases in baseline impedance were highly
      correlated with increases in power of non-ictal high frequency EEG activity.
      Seizures were accompanied by increases in impedance and all treatments induced
      transient, relatively large, increases in impedance often associated with
      unilateral reductions in low frequency EEG, likely periods of spreading
      depression. We conclude: cerebral cells swell in convulsant models of epilepsy,
      that there are pre-ictal accelerations in cell swelling, and that spreading
      depression-like events are frequently associated with seizures.

PMID- 16580142
TI  - Corticotropin releasing factor increases in brown adipose tissue thermogenesis
      and heart rate through dorsomedial hypothalamus and medullary raphe pallidus.
AB  - Corticotropin releasing factor, acting at hypothalamic corticotropin releasing
      factor receptors, contributes to the neural signaling pathways mediating stress
      related responses, as well as those involved in maintaining energy balance
      homeostasis. Sympathetically-regulated lipid metabolism and heat production in
      brown adipose tissue contributes to the non-shivering thermogenic component of
      stress-evoked hyperthermia and to energy expenditure aspects of body weight
      regulation. To identify potential central pathways through which hypothalamic
      corticotropin releasing factor influences brown adipose tissue thermogenesis,
      corticotropin releasing factor was microinjected into the lateral ventricle
      (i.c.v.) or into hypothalamic sites while recording sympathetic outflow to brown
      adipose tissue, brown adipose tissue temperature, expired CO2, heart rate and
      arterial pressure in urethane/chloralose-anesthetized, artificially-ventilated
      rats. I.c.v. corticotropin releasing factor or corticotropin releasing factor
      microinjection into the preoptic area or the dorsomedial hypothalamus, but not
      the paraventricular nucleus of the hypothalamus, elicited sustained increases in
      brown adipose tissue sympathetic nerve activity, brown adipose tissue
      temperature, expired CO2 and heart rate. These sympathetic responses to i.c.v.
      corticotropin releasing factor were eliminated by inhibition of neuronal activity
      in the dorsomedial hypothalamus or in the raphe pallidus, a putative site of
      sympathetic premotor neurons for brown adipose tissue, and were markedly reduced
      by microinjection of ionotropic glutamate receptor antagonists into the
      dorsomedial hypothalamus. The increases in brown adipose tissue sympathetic
      outflow, brown adipose tissue temperature and heart rate elicited from
      corticotropin releasing factor into the preoptic area were reversed by inhibition
      of neuronal discharge in dorsomedial hypothalamus. These data indicate that
      corticotropin releasing factor release within the preoptic area activates a
      sympathoexcitatory pathway to brown adipose tissue and to the heart, perhaps
      similar to that activated by increased prostaglandin production in the preoptic
      area, that includes neurons in the dorsomedial hypothalamus and in the raphe
      pallidus.

PMID- 16580143
TI  - Incorporation of embryonic CA3 cell grafts into the adult hippocampus at 4-months
      after injury: effects of combined neurotrophic supplementation and caspase
      inhibition.
AB  - As receptivity of the injured hippocampus to cell grafts decreases with time
      after injury, strategies that improve graft integration are necessary for graft
      mediated treatment of chronic neurodegenerative conditions such as temporal lobe
      epilepsy. We ascertained the efficacy of two distinct graft-augmentation
      strategies for improving the survival of embryonic day 19 hippocampal CA3 cell
      grafts placed into the adult hippocampus at 4-months after kainic acid induced
      injury. The donor cells were labeled with 5'-bromodeoxyuridine, and pre-treated
      and grafted with either brain-derived neurotrophic factor, neurotrophin-3 and a
      caspase inhibitor or fibroblast growth factor and caspase inhibitor. The yield of
      surviving grafted cells and neurons were quantified at 2-months post-grafting.
      The yield of surviving cells was substantially greater in grafts treated with
      brain-derived neurotrophic factor, neurotrophin-3 and caspase inhibitor (84%) or
      fibroblast growth factor and caspase inhibitor (99% of injected cells) than
      standard cell grafts (26%). Because approximately 85% of surviving grafted cells
      were neurons, increased yield in augmented groups reflects enhanced survival of
      grafted neurons. Evaluation of the mossy fiber synaptic re-organization in
      additional kainic acid-lesioned rats receiving grafts enriched with brain-derived
      neurotrophic factor, neurotrophin-3 and caspase inhibitor at 3-months post
      grafting revealed reduced aberrant dentate mossy fiber sprouting in the dentate
      supragranular layer than "lesion-only" rats at 4 months post-kainic acid,
      suggesting that some of the aberrantly sprouted mossy fibers in the dentate
      supragranular layer withdraw when apt target cells (i.e. grafted neurons) become
      available in their vicinity. Thus, the yield of surviving neurons from CA3 cell
      grafts placed into the adult hippocampus at an extended time-point after injury
      could be enhanced through apt neurotrophic supplementation and caspase
      inhibition. Apt grafting is also efficacious for reversing some of the abnormal
      synaptic reorganization prevalent in the hippocampus at later time-points after
      injury.

PMID- 16580144
TI  - Inhibitory M2 muscarinic receptors are upregulated in both axotomized and intact
      small diameter dorsal root ganglion cells after peripheral nerve injury.
AB  - Acetylcholine reduces nociceptive input in part by activating inhibitory M2
      muscarinic receptors on primary sensory neurons, and acetylcholinesterase
      inhibitors and muscarinic agonists produce analgesia in humans and animals. M2
      muscarinic receptors are upregulated in animals with diabetic neuropathy, but
      their level of expression and function after peripheral nerve injury has not been
      previously examined. This study tested, using intracellular Ca(2+) response to
      membrane depolarization, the effect of the M2 muscarinic receptor agonist
      bethanechol on individual dorsal root ganglion cells from normal and L5-6 spinal
      nerve-ligated rats, followed by M2 muscarinic receptor immunostaining. We also
      examined functional transient receptor potential for vanilloids-1 activity by
      determining intracellular Ca(2+) response evoked by capsaicin in M2 muscarinic
      receptor immunoreactive cells. In normal dorsal root ganglion cells, bethanechol
      inhibited the Ca(2+) response in a concentration-related fashion, and this
      inhibition was blocked by the M2 muscarinic receptor antagonist gallamine. Cells
      expressing M2 muscarinic receptors by immunostaining were significantly inhibited
      by bethanechol, whereas those lacking positive staining were not. The proportion
      of studied dorsal root ganglion neurons with positive M2 muscarinic receptor
      staining increased significantly in the injured ipsilateral L5-6 and the
      uninjured ipsilateral L4 ganglia, but not in the contralateral dorsal root
      ganglion neurons compared with normals. In contrast, the proportion of neurons
      responding to capsaicin significantly decreased in the injured ipsilateral L5-6
      dorsal root ganglion cells. These results suggest that inhibitory M2 muscarinic
      receptors are upregulated in small- and medium-sized axotomized dorsal root
      ganglion neurons and their uninjured neighbors following nerve injury, and may
      represent an appropriate target for analgesia in this setting.

PMID- 16580145
TI  - Neonatal lesions of the ventral hippocampus in rats lead to prefrontal cognitive
      deficits at two maturational stages.
AB  - This experiment assessed the effect of neonatal ventral hippocampus lesions in
      rats, a heuristic approach to model schizophrenia, on continuous delayed
      alternation and conditional discrimination learning performance before and after
      complete cerebral maturation. Delays (0, 5, 15, and 30 s) were introduced in the
      tasks to help dissociate between a hippocampal and a prefrontal cortex
      dysfunction. At postnatal day (PND) 6 or 7, rats received bilateral
      microinjections of ibotenic acid or phosphate-buffered saline in the ventral
      hippocampus. From PND 26 to PND 35, rats were tested on the alternation task in a
      T-maze; from PND 47 to PND 85, the same rats were tested in the discrimination
      task where a stimulus and a response location had to be paired. Deficits in
      ventral hippocampus-lesioned rats were observed in both tasks whether a delay was
      introduced before a response or not. Impaired performance regardless of delay
      length, combined with high rates of perseverative errors, suggested a post
      lesional prefrontal cortex dysfunction which persisted from the juvenile stage
      into adulthood. Premature cognitive impairments could not be predicted on the
      basis of the neurodevelopmental animal model of schizophrenia. Nevertheless, they
      appear consistent with accounts of premorbidly compromised memory, both immediate
      and delayed, in subgroups of schizophrenia patients.

PMID- 16580147
TI  - Activation by p-chloroamphetamine of the spinal ejaculatory pattern generator in
      anaesthetized male rats.
AB  - In urethane-anesthetized male rats, a branch of the hypogastric nerve was shown,
      anatomically and electrophysiologically, to supply the vas deferens. Recordings
      from this nerve revealed a low level of tonic activity, which was predominantly
      efferent motor activity. Administration of p-chloroamphetamine i.v., elicited a
      rhythmic burst of neuronal activity, coherent with rhythmic pressure increases in
      the vas deferens and contractions of the bulbospongiosus muscles, which together
      comprise ejaculation. This response to p-chloroamphetamine was still present
      after complete transection of the spinal cord at T8-T9. These data indicate that
      p-chloroamphetamine is capable of activating the spinal neuronal circuits that
      generate the pattern of autonomic and somatic responses similar to those of
      sexual climax. Furthermore based on the best documented action of p
      chloroamphetamine, the results suggest that the excitability of the pattern
      generator is regulated by serotonergic, dopaminergic or noradrenergic receptors
      in the lumbosacral spinal cord. We conclude this animal model will enable robust
      studies of the pharmacology and physiology of central neural mechanisms involved
      in ejaculation and sexual climax.

PMID- 16580146
TI  - Novel localization of CD38 in perivascular sympathetic nerve terminals.
AB  - Using high performance liquid chromatography fraction analysis we have recently
      established that numerous smooth muscle preparations, including the canine
      mesenteric artery and vein, release beta-nicotinamide adenine dinucleotide upon
      short-pulse electrical field stimulation in tetrodotoxin- and omega-conotoxin
      GVIA-sensitive manners [ Release of beta-nicotinamide adenine dinucleotide upon
      stimulation of postganglionic nerve terminals in blood vessels and urinary
      bladder. J Biol Chem 279:48893-48903.]. The beta-nicotinamide adenine
      dinucleotide metabolites ADP-ribose and cyclic ADP-ribose are also present in the
      tissue superfusates. CD38 is a multifunctional enzyme involved in the degradation
      of beta-nicotinamide adenine dinucleotide to ADP-ribose and cyclic ADP-ribose.
      Western immunoblot analysis revealed that CD38 is expressed in both artery and
      vein. Confocal laser scanning microscopy established colocalization of CD38 with
      tyrosine hydroxylase, synaptotagmin and synaptic vesicle protein in both blood
      vessels. High performance liquid chromatography with fluorescence detection
      demonstrated that whole tissue segments metabolize 1,N(6)-etheno-nicotinamide
      adenine dinucleotide to 1,N(6)-etheno-ADP-ribose and nicotinamide-guanine
      dinucleotide to cyclic GDP-ribose, suggesting the presence of both nicotinamide
      adenine dinucleotide-glycohydrolase and ADP-ribosyl cyclase activities in these
      blood vessels. Both enzymes appear to be associated with the membrane fraction,
      and therefore might be attributed to CD38. These data demonstrate a previously
      uncharacterized localization of CD38 in perivascular autonomic nerve terminals.
      Therefore, the beta-nicotinamide adenine dinucleotide/CD38 system may provide new
      mechanisms in autonomic neurovascular control.

PMID- 16580148
TI  - Absence of Reelin results in altered nociception and aberrant neuronal
      positioning in the dorsal spinal cord.
AB  - Mutations in reeler, the gene coding for the Reelin protein, result in pronounced
      motor deficits associated with positioning errors (i.e. ectopic locations) in the
      cerebral and cerebellar cortices. In this study we provide the first evidence
      that the reeler mutant also has profound sensory defects. We focused on the
      dorsal horn of the spinal cord, which receives inputs from small diameter primary
      afferents and processes information about noxious, painful stimulation. We used
      immunocytochemistry to map the distribution of Reelin and Disabled-1 (the protein
      product of the reeler gene, and the intracellular adaptor protein, Dab1, involved
      in its signaling pathway) in adjacent regions of the developing dorsal horn, from
      early to late embryonic development. As high levels of Dab1 accumulate in cells
      that sustain positioning errors in reeler mutants, our findings of increased Dab1
      immunoreactivity in reeler laminae I-III, lamina V and the lateral spinal nucleus
      suggest that there are incorrectly located neurons in the reeler dorsal horn.
      Subsequently, we identified an aberrant neuronal compaction in reeler lamina I
      and a reduction of neurons in the lateral spinal nucleus throughout the spinal
      cord. Additionally, we detected neurokinin-1 receptors expressed by Dab1-labeled
      neurons in reeler laminae I-III and the lateral spinal nucleus. Consistent with
      these anatomical abnormalities having functional consequences, we found a
      significant reduction in mechanical sensitivity and a pronounced thermal
      hyperalgesia (increased pain sensitivity) in reeler compared with control mice.
      As the nociceptors in control and reeler dorsal root ganglia are similar, our
      results indicate that Reelin signaling is an essential contributor to the normal
      development of central circuits that underlie nociceptive processing and pain.

PMID- 16580150
TI  - Excuses to continue smoking: the role of disengagement beliefs in smoking
      cessation.
AB  - BACKGROUND: The aim of the present study was to investigate the role of
      disengagement beliefs in smoking cessation. The association of disengagement
      beliefs with forward transition through the transtheoretical stages of change and
      self-reported quitting were examined, with and without adjusting for processes of
      change. METHODS: A longitudinal survey was conducted among Dutch smokers,
      resulting in 367 respondents who completed two questionnaires, one at baseline
      and one at 8 months follow-up. Disengagement beliefs, intention to quit, actual
      quitting, and the processes of change were assessed. RESULTS: The findings showed
      that disengagement beliefs were negatively associated with forward stage
      transition and actual quitting. Processes of change only partly mediated these
      associations. CONCLUSIONS: Adhering to disengagement beliefs seems to be an
      inhibitor of progression towards smoking cessation and actual quitting, also
      after adjustment for processes of change.

PMID- 16580149
TI  - Preservation of the direct and indirect pathways in an in vitro preparation of
      the mouse basal ganglia.
AB  - We have developed a slice preparation of the mouse basal ganglia which contains
      portions of the striatum, external pallidum, subthalamic nucleus and substantia
      nigra and the neocortex. This basal ganglia slice is unique in preserving
      functional direct and indirect connections between the striatum and the
      substantia nigra as well as interconnectivity between the globus pallidus and the
      subthalamic nucleus. We used fiber tract tracing studies and electrophysiological
      recordings to demonstrate the full functionality of these pathways. Deposits of
      1,1'-dioctadecyl-3,3,3',3'-tetra-methylindocarbocyamine perchlorate in the
      different basal ganglia resulted in labeled fibers in each of their target
      nuclei. Confirming these results, electrical stimulation of the different nuclei
      elicited whole-cell recorded postsynaptic potentials in their target neurons with
      an appropriate pharmacological profile. Electrical and glutamate activation of
      the striatum evoked bursts of glutamatergic and GABAergic activities in whole
      cell recorded nigral neurons indicating that the direct and indirect pathways are
      operative in this slice. It also showed that the responses evoked are not due to
      fibers en passant but to the activation of striatal cell bodies. These findings
      provide the first direct evidence for a preserved basal ganglia circuitry in
      vitro and make the basal ganglia slice a suitable preparation for analyzing the
      activity of the direct and indirect pathways in physiological and pathological
      conditions.

PMID- 16580151
TI  - The consumption of alcohol by Australian adolescents: a comparison of revenue and
      expenditure.
AB  - AIMS: To estimate (i) Australian government taxation revenue collected from the
      consumption of alcohol by adolescents and (ii) the amount spent by the government
      on interventions aimed at educating adolescents about the potential dangers of
      alcohol use. DESIGN: Secondary data analysis. SETTING: Australia. FINDINGS:
      Australian adolescents (aged between 12 and 17 years, inclusive) spent
      approximately US dollars 217 million on alcoholic beverages in 2002, netting the
      Australian government approximately US dollars 112 million in tax revenue. This
      resulted in an average of US dollars 195 earned in tax per adolescent drinker. It
      is estimated that the Government spent approximately US dollars 17 million on
      adolescent drinking interventions in 2002, equating to an expenditure of about US
      dollars 10.51 per adolescent on the delivery of alcohol interventions. For every
      dollar spent on alcohol interventions aimed at adolescents, it is estimated that
      the government receives around US dollars 7 in alcohol tax revenue. CONCLUSIONS:
      A substantial disparity exists between the amount of tax revenue received by the
      Australian government from adolescent drinkers and the overall amount spent in
      attempting to prevent and relieve some of the problems associated with adolescent
      problem drinking.

PMID- 16580152
TI  - Differences in smoking-related variables based on phenylthiocarbamide "taster"
      status.
AB  - Test strips impregnated with phenylthiocarbamide (PTC) have been used to identify
      genetic differences based on whether a bitter taste is perceived. To determine
      whether smokers who perceive PTC as bitter tasting ("tasters") would differ from
      those who describe it as tasteless ("non-tasters") on smoking-related variables,
      we studied 464 current smokers (70% female, 79% White; mean age 30.5+/-9 years)
      recruited to participate in laboratory experiments and clinical trials. Of these,
      217 (47%) reported the PTC strips as tasteless and 154 (33%) as tasting bitter.
      The remaining 93 (20%) described the taste as salty, sweet, or other and were
      excluded from further analyses. Comparing tasters with non-tasters, we found
      significant differences in mean (S.D.) total years smoked (14.5 [9.2] for non
      tasters, vs. 12.6 [8.4] for tasters, p<.05), Fagerstrom Tolerance Questionnaire
      scores (6.4 [2.1] vs. 5.8 [2.1], p<.01), and scores on the Positive Reinforcement
      scale of the Michigan-Nicotine Reinforcement Questionnaire (8.1 [2.9] vs. 6.8
      [3.1], p<.05). Results suggest that among smokers, ability to taste PTC may
      confer some protection from development of nicotine dependence and positive
      reinforcement from smoking.

PMID- 16580153
TI  - A model linking biology, behavior and psychiatric diagnoses in perpetrators of
      domestic violence.
AB  - Research indicates that perpetrators of domestic violence have abnormalities in
      central serotonin and testosterone metabolism, an increased sensitivity to
      anxiogenic stimuli, and an impaired neuro-connection between their cortex and the
      amygdala. Clinical evaluations show that perpetrators of domestic violence also
      have a distinguishing set of behaviors and diagnoses related to anxiety,
      depression, intermittent explosive disorder, and borderline personality disorder.
      In this paper we propose a model to understand how the biological abnormalities
      can potentially explain the behaviors and diagnoses exhibited by the
      perpetrators. Changes in the perpetrator's neurotransmitters lead to a heightened
      sensitivity to environmental stimuli, anxiety, and conditioned fear. Lack of
      cortical input to the amygdala impairs the perpetrator's ability to extinguish
      anxiety and/or conditioned fear and gives rise to either innate behaviors (e.g.,
      fight, flight, and shut down) or learned fear avoidant behaviors designed to
      avoid anxiety (e.g., alcohol consumption, self-injurious acts, and obsessive
      behaviors). Linking conditioned fear and fear avoidance to the behaviors and
      psychiatric diagnoses will serve to change the way the medical community
      perceives and treats perpetrators of domestic violence.

PMID- 16580154
TI  - Impact of formulation on the abuse liability, safety and regulation of
      medications: the expert panel report.
AB  - A scientific meeting was held in April 2005 to consider how the formulation of
      medications might impact on their potential for abuse. The background papers
      prepared for this meeting, as well as abstracts of volunteered presentations, are
      published in this supplemental issue of Drug and Alcohol Dependence. This paper
      is the Expert Panel Report summarizing the discussions held following the formal
      presentations and including the suggested recommendations for additional research
      that emerged from these discussions. There was overwhelming consensus that
      formulation does play a role in prescription drug abuse, i.e., a formulation of
      an abused substance can be developed that will decrease its abuse potential, and
      several examples were cited. Nevertheless, it is imperative that new formulations
      have similar efficacy and in no way compromise medication access to doctors and
      patients. However, there was also consensus that a great deal of research and
      discussion was needed to fully implement a program of risk management through
      reformulation of existing products or tailoring the formulation of new products
      to retain clinical efficacy and safety while minimizing potential for abuse.
      Those who need to take part in this discussion include scientific groups,
      pharmaceutical companies, as well as governmental and regulatory agencies. The
      areas where more research is needed include development of standards for
      assessing tamper-resistance, improved animal models that can address formulation
      related variables (e.g., onset, duration), the redesign of human laboratory
      studies providing appropriate models for comparing formulations, and improved
      post-marketing surveillance. Finally, knowledge and experience are needed to
      translate scientific work into a predictable, transparent and reliable regulatory
      process.

PMID- 16580155
TI  - Ultrastructural and morphometric characterization of buffalo (Bubalus bubalis)
      ovarian preantral follicles.
AB  - The main objective of the present study was to characterize buffalo preantral
      ovarian follicles. Parts of ovarian cortex, collected from postpubertal buffalo
      females that were having estrous cycles at regular intervals, were selected under
      stereomicroscopy and processed for optic and transmission electron microscopy.
      Primordial follicles were characterized as an oocyte encircled by one layer of
      flattened cells. The buffalo primordial follicle has a mean diameter of 35 microm
      and the oocyte diameter is 24.9 microm. The oocyte nucleus is relatively large
      and eccentric; and in the cytoplasm a large amount of mitochondria, vesicles and
      endoplasmic reticulum cistern, mainly of the smooth type is observed. The
      primordial follicles cells are rich in plasma membrane invaginations, which are
      observed within the cell and between the cell and the oocyte. The primary
      follicles (mean diameter of 41.8 microm) consist of an oocyte, with a medium
      diameter of 26.9 microm, surrounded by one layer of cubical granulosa cells. At
      this follicular stage, the beginning of zona pellucida deposition can also be
      seen in areas between the oocyte and follicular cells. The secondary follicles,
      which are surrounded by more than one layer of cubical cells, have a diameter of
      53.3 microm, and the oocyte has a mean diameter of 29.4 microm. The
      ultrastructural analysis showed a large amount of coalescent vesicles, more
      evident in the oocyte periphery. The zona pellucida (ZP) is thicker at this stage
      and contains a large quantity of glycoproteins. In general, the ultrastructure of
      buffalo preantral follicles was similar to that of other mammalian species, but
      some differences were observed, which indicate species specific characteristics.
      The main differences observed were cytoplasmic vesicles quantity, mitochondria
      shape and inner content, ZP deposition and granulosa cell-oocyte junctions. In
      conclusion, the morphological differences described in this paper, could be
      responsible for some functional differences observed in Bubalus bubalis in vitro
      embryo production and follicular dynamics, when compared with Bos taurus or Bos
      indicus species.

PMID- 16580156
TI  - Comparison of fundamental voice frequency between menopausal women and women at
      menacme.
AB  - OBJECTIVE: To analyze comparatively the speaking fundamental frequency (F0)
      between women at menacme and women in the climacterium taking or not hormonal
      replacement therapy. METHODS: A controlled transverse study was conducted on 45
      women divided into three groups of 15 women each: Group A (women aged 20-40 years
      with regular menstrual cycles taking no hormonal contraceptives), Group B (women
      aged 45-60 years with a duration of menopause of at least 2 years taking 1mg
      estradiol valerate +90 microg norgestimate per day in a continuous treatment
      scheme lasting at least 6 months), and Group C (women aged 45-60 years with a
      duration of menopause of at least 2 years taking no HRT for at least 6 months).
      The mean age for Groups A, B and C was 30.3, 54.5 and 56.5 years, respectively.
      The groups were analyzed comparatively regarding F0 values for the sustained
      vowels /e/ and /i/. RESULTS: Mean F0 for the sustained vowels /e/ and /i/ were
      215.97 and 229.89 Hz, 206.21 and 221.79 Hz, 200.71 and 212.79 Hz for Groups A, B
      and C, respectively, with no significant differences between groups. CONCLUSIONS:
      Although there is evidence of a probable modulating effect of sex steroids on the
      larynx, in the present study no significant differences in speaking voice were
      observed regarding menopause or the use of HRT. The absence of such differences
      observed in F0 does not necessarily mean that there is no difference in vocal
      quality between these groups since F0 represents only a vocal parameter.

PMID- 16580157
TI  - Comment to "seasonal onset of the menopause".

PMID- 16580159
TI  - Oral bioavailability of cyclosporine: solid lipid nanoparticles (SLN) versus drug
      nanocrystals.
AB  - For the development of an optimized oral formulation for cyclosporine A, 2% of
      this drug has been formulated in solid lipid nanoparticles (SLN, mean size 157
      nm) and as nanocrystals (mean size 962 nm). The encapsulation rate of SLN was
      found to be 96.1%. Nanocrystals are composed of 100% of drug. For the assessment
      of the pharmacokinetic parameters the developed formulations have been
      administered via oral route to three young pigs. Comparison studies with a
      commercial Sandimmun Neoral/Optoral used as reference have been performed. The
      blood profiles observed after oral administration of the commercial microemulsion
      Sandimmun revealed a fast absorption of drug leading to the observation of a
      plasma peak above 1,000 ng/ml within the first 2 h. For drug nanocrystals most of
      the blood concentrations were in the range between 30 and 70 ng/ml over a period
      of 14 h. These values were very low, showing huge differences between the
      measuring time points and between the tested animals. On the contrary,
      administration of cyclosporine-loaded SLN led to a mean plasma profile with
      almost similarly low variations in comparison to the reference microemulsion,
      however with no initial blood peak as observed with the Sandimmun Neoral/Optoral.
      Comparing the area under the curves (AUC) obtained with the tested animals it
      could be stated that the SLN formulation avoids side effects by lacking blood
      concentrations higher than 1,000 ng/ml. In this study it has been proved that
      using SLN as a drug carrier for oral administration of cyclosporine A a low
      variation in bioavailability of the drug and simultaneously avoiding the plasma
      peak typical of the first Sandimmun formulation can be achieved.

PMID- 16580158
TI  - Solubilization of monovalent weak electrolytes by micellization or complexation.
AB  - In order to prepare a liquid formulation for a weak electrolyte, micellization or
      complexation is often applied with the solution pH controlled to have some of the
      drug molecules ionized. The efficiency of the micellization is evaluated by
      either the micellar solubilization capacities, kappau, and kappai or the micellar
      partition coefficients, Ku(m) and Ki(m), for the unionized and ionized drug
      species. Similarly, the efficiency of complexation is evaluated by either the
      complex solubilization capacities, tauu and taui or the drug-ligand binding
      constants,Ku(1:1) and Ki(1:1). In this study, the experimental values of these
      descriptors were generated for seven ionizable drugs. The relationships of the
      logarithms of each descriptor to the logarithm of the octanol-water partition
      coefficient of the unionized drug (log Pu) and ionized drug species (log Pi) were
      evaluated. Although kappa and tau cannot be predicted, this study shows that Km
      and K1:1 are dependent on log P for both the unionized and ionized drug species.
      Thus, the total drug solubility for a weak electrolyte solubilized by
      micellization or complexation can be predicted at any pH.

PMID- 16580160
TI  - Intratracheal and subcutaneous liposomal VIP normalizes arterial pressure in
      spontaneously hypertensive hamsters.
AB  - We determined whether a single intratracheal and subcutaneous administration of
      biocompatible and biodegradable vasoactive intestinal peptide self-associated
      with sterically stabilized liposomes (VIP-SSL) normalizes mean arterial pressure
      (MAP) in spontaneously hypertensive hamsters (SHH). We found that VIP-SSL (0.1
      nmol) administered by either routes normalizes MAP (p < 0.05). Maximal effect was
      observed within 10-20 min and lasted for 6 h. VIP-SSL had no significant effects
      on heart rate. VIP alone (0.1 nmol) and empty SSL had no significant effects on
      MAP. VIP-SSL (0.1 nmol) had no significant effects on MAP and heart rate in
      age/genetically-matched control hamsters. Given these data, we suggest that
      pulmonary and subcutaneous delivery of VIP-SSL should be further developed as
      peptide nanomedicine for essential hypertension.

PMID- 16580161
TI  - Potential use of drug carried-liposomes for cancer therapy via direct
      intratumoral injection.
AB  - Liposomes have recognized advantages as nano-particle drug carriers for tumor
      therapy. In this study, the pharmacokinetics and distribution of intratumorally
      administered liposomes were investigated as drug carriers for treating solid
      tumors via direct intratumoral administration. 99mTc-liposomes were administered
      intratumorally to nude rats bearing human head and neck squamous cell carcinoma
      xenografts. Planar gamma camera images were analyzed to evaluate the local
      retention of the intratumorally administered liposomes. Co-registered pinhole
      micro-single photon emission computed tomography (SPECT)/computed tomography (CT)
      images were acquired of the whole animal as well as the dissected tumors to
      determine intratumoral distribution of the 99mTc-liposomes. For 99mTc-liposomes,
      there was an initial retention of 47.4 +/- 11.0% (n = 4) in tumors and
      surrounding tissues. At 20 h, 39.2 +/- 10.6% (n = 4) of 99mTc-activity still
      remained in the tumor. In contrast, only 18.7 +/- 3.3% (n = 3) of the
      intratumoral 99mTc-activity remained for unencapsulated 99mTc-complex at 20 h.
      Pinhole micro-SPECT images demonstrated that 99mTc-liposomes also have a superior
      intratumoral 99mTc-activity diffusion compared with unencapsulated 99mTc-complex.
      Higher intratumoral retention of 99mTc-liposomes accompanied by an improved
      intratumoral diffusion suggests that intratumorally administered liposomal drugs
      are potentially promising agents for solid tumor local therapy.

PMID- 16580162
TI  - Age related changes in the distribution of laryngeal glands in the human adult
      larynx.
AB  - OBJECTIVE: To understand the defense status of glandular tissue in the human
      adult larynx, we examined the glandular distribution, concentration and the ratio
      of the mucous glands in the subglottic and supraglottic larynx. METHODS: One
      hundred and seven adult larynges were examined. The area of the mucosa and glands
      were measured using an image analyzing system. The correlations of the
      concentration as well as the ratio of the mucous glands with age were analyzed.
      RESULTS: The ratio of the areas occupied by the glandular acini of the subglottis
      was almost equal to that of infants as we reported earlier. The concentration of
      the laryngeal glands decreased in higher-aged adults at the level of the
      supraglottis, but not at the level of the subglottis. CONCLUSIONS: In comparison
      to infants, the ratio of laryngeal glands of the human subglottic larynx is
      rather constant in human adults. However, the supraglottic larynx seems to be
      influenced by increasing age. The changes deserved in the laryngeal glands
      predominantly occur in the supraglottic larynx.

PMID- 16580163
TI  - [Are isolation measures needed in the hospital management of Acinetobacter
      baumannii colonizations-infections?].
AB  - Until 2001, the infection control department of the Besancon university hospital
      (France) recommended isolation precautions for all patients colonized-infected by
      Acinetobacter baumannii (Ab) whatever the antibiotic susceptibility of the
      strain. These systematic isolation procedures were given up at the beginning of
      2002 since the number of colonized-infected patients remained stable from 1998 to
      2001. OBJECTIVE: The aim of this study was to evaluate the impact of this
      decision on the risk of Ab infection. METHOD: Incidence rates of colonization
      infections that were observed during years 2002 and 2003 were compared with
      expected incidence rate, based on data from 1998-2001 period. Infection control
      practices and antibiotics consumption were evaluated for each ward of
      hospitalisation. Genotyping made it possible to determine diversity of clones
      inside each unit and the whole hospital. RESULTS: The expected incidence per 1000
      patients-days was 0.22 in comparison with observed data in 2002, 0.34 (CI(95%)
      [0.28-0.42]), and in 2003, 0.53 (CI(95%) [0.45-0.63]). The expected number of Ab
      bloodstream infections, about two per year compared with the observed numbers in
      2002 and 2003 respectively seven and 17. The number of unit with more than three
      cases per year increased from seven in 1999 to 18 in 2003. Antibiotics
      consumption did not change significantly. CONCLUSION: Genotyping results show the
      importance of cross-transmission in these units. Finally, observed results
      suggest that some measures of isolation precautions in addition to standard
      precautions are needed to prevent outbreaks of Ab.

PMID- 16580165
TI  - Pneumocystis jirovecii genotypes and granulomatous pneumocystosis.
AB  - This study describes the initial data concerning molecular typing of Pneumocystis
      jirovecii in a patient having developed granulomatous Pneumocystis pneumonia
      (PCP). Three types, B(1)a(3), B(1)a(4), B(1)b(2), were identified. All three had
      been described in reports concerning patients with common diffuse alveolar PCP.
      The present data show that identical microorganisms can be involved in both
      granulomatous PCP and diffuse alveolar PCP and that the pathogenesis of the
      granulomatous response to P. jirovecii may more likely be related to host
      factors.

PMID- 16580164
TI  - [Screening for bacteriuria in diabetic patients. Is it possible to stop
      systematic urine cytobacteriological testing?].
AB  - OBJECTIVES AND METHOD: The discordance between test by urine dipstick (nitrites
      and leucocyte-esterase) and analysis in laboratory, with urinary culture on the
      same sample was studied in diabetic patients, from October 2000 to May 2002, to
      eventually stop systematic laboratory test. The dipstick result (Clinitek 20
      Bayer) was classified as "possibility of bacteriuria" if one of the two tests was
      positive. Bacteriuria was considered significant if the laboratory test result
      gave, at least 10(5) bacteria per mL, (one strain), and at least 10(4)
      leucocytes. The out point was the dipstick negative predictive value (NPV).
      RESULTS: The study included 683 patients. The dipstick result was "possibility of
      bacteriuria" in 153 cases (22.4%). Thirty-nine bacteriuria (5.7%) were reported,
      including 2 dipstick false negatives. The NPV was 99.6% [IC 95% : 99.1-100].
      CONCLUSION: The systematic laboratory tests were stopped.

PMID- 16580166
TI  - [Central-venous-catheter-related bacteremia in neonatalogy].
AB  - OBJECTIVE: The aim of this retrospective study was to identify the risk factors
      for catheter-associated bloodstream infection (CABSI) in neonates. METHOD AND
      RESULTS: Fifteen episodes of CABSI occurred in 108 central catheters over a
      period of one year (2002). The univariate analysis risk factors were birth weight
      (1.064 vs 1.413 g; P<0.001), gestation age (28 vs 31 weeks; P<0.001), blood
      transfusion (8/15 vs 3/34; P<0.01), corticosteroids (7/15 vs 3/34; P<0.01), nasal
      CPAP duration (13.6 vs 2 days; P<0.01). Nasal CPAP duration was the only risk
      factor independently associated with CASBI (OR=1.2, 95% confidence interval=1.09
      1.5) in the multivariate logistic regression analysis. CONCLUSIONS: The risk of
      infection associated with low birth weight is multifactorial suggesting that host
      related factors are important. Prevention remains difficult and a policy of
      strict aseptic catheter care must be promoted.

PMID- 16580167
TI  - A rapid and simple procedure for the determination of ephedrine alkaloids in
      dietary supplements by gas chromatography-mass spectrometry.
AB  - A simple method for the determination of ephedrine alkaloids: ephedrine (EF),
      pseudoephedrine (PE), norpseudoephedrine (NPE), norephedrine (NE) and
      methylpseudoephedrine (MPE) in dietary supplements by gas chromatography-mass
      spectrometry is described. After the addition of 3,4
      methylenedioxypropylamphetamine as internal standard, a liquid-liquid extraction
      procedure in alkaline conditions with chloroform/isopropanol (9:1, v/v) was
      applied to the samples prior to analysis. Chromatography was performed on a fused
      capillary column and analytes, derivatized with pentafluoropropionic anhydride,
      were determined in the selected-ion-monitoring (SIM) mode. The method was
      validated in the range 0.3-10 microg/mg for EP, 0.06-2.5 microg/mg for PE and NPE
      and 0.04-1 microg/mg NE and MPE. Mean recovery ranged between 65.7 and 81.3% for
      the different analytes in dietary supplements. The quantification limits were 0.3
      microg/mg for EP, 0.06 microg/mg for PE, 0.04 microg/mg for NPE, NE and MPE. The
      method was applied to analysis of various dietary supplements containing Ma-huang
      (Ephedra Sinica) and Sida Cordifolia plant extracts promoted for aiding weight
      control and boosting sports performance and energy.

PMID- 16580168
TI  - Determination of hesperidin in Pericarpium Citri Reticulatae by semi-micro HPLC
      with electrochemical detection.
AB  - Determination of hesperidin contents in Pericarpium Citri Reticulatae was
      performed by a simple extraction with methanol and semi-micro high-performance
      liquid chromatography with electrochemical detection (muHPLC-ECD). Chromatography
      was performed using a microbore octadecylsilica (ODS) column, methanol-water
      phosphoric acid (40:60:0.5, v/v/v), as a mobile phase and applied potential at
      +0.9 V versus Ag/AgCl. Peak heights were found linearly related to the
      concentrations of hesperidin injected 9.16 ng/ml to 3.06 microg/ml (r>0.999). The
      detection limit (S/N=3) was 3.06 ng/ml (15.3 pg). Hesperidin of 305 ng/ml was
      detected with a relative standard deviation (R.S.D.) of 0.79% (n=5). Hesperidin
      in Pericarpium Citri Reticulatae was extracted with methanol, diluted with the
      mobile phase, and injected into the muHPLC-ECD for determination. The hesperidin
      content of Pericarpium Citri Reticulatae from four different districts in China
      were determined with R.S.D. of 3.59%, 2.29%, 2.36%, and 2.32% (n=5),
      respectively. Recoveries of hesperidin from the four Pericarpium Citri
      Reticulatae sources were 100.3%, 99.83%, 100.7%, and 100.6%, respectively. This
      method is useful for the determination of hesperidin in Pericarpium Citri
      Reticulatae, and especially so for instances when samples are sparse.

PMID- 16580169
TI  - Kinetics of photooxidation of papaverine hydrochloride and its major
      photooxidation products.
AB  - HPCE methodology was modified to be used in kinetic experiments on photooxidation
      reactions of papaverine hydrochloride 1 and its oxidation products (papaverinol 2
      and papaveraldine hydrochloride 3) chloroform solutions exposed to UV254 light in
      aerobic conditions. On photooxygenation of the above compounds is formed the
      final degradation product, a brown compound X 4, 2,3,9,10-tetramethoxy-12-oxo-12H
      indolo[2,1-a]isoquinolinylim chloride. The rate of 4 formation from the above
      compounds can be given as 2>3>1>1 HCl. The photooxidation reactions of 1 and 2
      proceed with pseudo first-order kinetics and that reaction for 3 follows zero
      order kinetics. The most labile compound is 2 whose half-life time is 2.4 times
      shorter than that one of 1 HCL. The most stable product is 3 whose half-life time
      is 31-fold longer than of 2. The specific quantum yields are equal 0.28, 0.30 and
      0.10 for 1 HCl, 2 and 3, respectively which confirm the above stability pattern
      of the compounds concerned.

PMID- 16580170
TI  - Validated chiral liquid chromatographic method for the enantiomeric separation of
      Pramipexole dihydrochloride monohydrate.
AB  - A chiral liquid chromatographic method was developed for the enantiomeric
      resolution of Pramipexole dihydrochloride monohydrate, (S)-2-amino-4,5,6,7-tetra
      hydro-6-(propylamino) benzothiazole dihydrochloride monohydrate, a dopamine
      agonist in bulk drugs. The enantiomers of Pramipexole dihydrochloride monohydrate
      were resolved on a Chiralpak AD (250 mm x 4.6 mm, 10 microm) column using a
      mobile phase system containing n-hexane:ethanol:diethylamine (70:30:0.1, v/v/v).
      The resolution between the enantiomers was found not less than eight. The
      presence of diethylamine in the mobile phase has played an important role in
      enhancing chromatographic efficiency and resolution between the enantiomers. The
      developed method was extensively validated and proved to be robust. The limit of
      detection and limit of quantification of (R)-enantiomer were found to be 300 and
      900 ng/ml, respectively for 20 microl injection volume. The percentage recovery
      of (R)-enantiomer was ranged from 97.3 to 102.0 in bulk drug samples of
      Pramipexole dihydrochloride monohydrate. Pramipexole dihydrochloride monohydrate
      sample solution and mobile phase were found to be stable for at least 48 h. The
      proposed method was found to be suitable and accurate for the quantitative
      determination of (R)-enantiomer in bulk drugs.

PMID- 16580171
TI  - Effects of ACTH injections during estrus on concentrations and patterns of
      progesterone, estradiol, LH, and inhibin alpha and time of ovulation in the sow.
AB  - This study investigated whether injections of ACTH for 48 h, from the onset of
      the second standing estrus after weaning, had any impact on time of ovulation and
      patterns of progesterone, estradiol, luteinizing hormone (LH), and inhibin alpha.
      The studied sows (n=15) were fitted with jugular vein catheters and randomly
      divided into a control (C group) and an ACTH group. From the onset of standing
      estrus, the sows were injected (NaCl or synthetic ACTH, 5 microg/kg) every 4h;
      blood samples were collected immediately before and 45 min after each injection.
      Ovulation was monitored using ultrasonography. The ACTH-group sows stopped
      displaying signs of standing estrus sooner after ovulation in their second
      estrus, but no impact was found on time of ovulation. There were no significant
      differences in the intervals between LH peak, estradiol peak, and the onset of
      standing estrus between the C and ACTH groups. The cortisol and progesterone
      concentrations were significantly elevated (p<0.001) in samples taken 45 min
      after ACTH injection. There were minor differences in estradiol and LH
      concentrations between the groups. Overall inhibin alpha concentrations were
      significantly higher during the treatment period in the ACTH than in the C group,
      but there were no significant differences between samples taken either 45 min or
      4h after injection. In conclusion, injections of synthetic ACTH during estrus in
      the sow apparently disturb the duration of signs of standing estrus and the
      hormonal pattern of progesterone, and possibly of inhibin alpha, estradiol and
      LH.

PMID- 16580172
TI  - Surgical treatment of liver metastases of colorectal cancer: Strategies and
      controversies in 2006.
AB  - AIMS: To review the latest strategies and controversies in the surgical treatment
      of liver metastases of colorectal cancer systemically and comprehensively.
      METHODS: A medline based literature search on relevant topics was performed in
      PubMed for key articles concerning the novel strategies and controversies in the
      management of liver metastases of colorectal cancer. Some information was
      obtained from 'Proc Am Soc Clin Oncol' published recently. The findings and
      discussions were related to our own experiences. RESULTS: Although for well
      indicated patients, a consensus has been reached that hepatic resection is the
      only management that could provide the patients curability, there still exist
      many controversies, such as the prognostic evaluation, contraindications to
      hepatic resection, treatment for synchronous liver metastases, the place of
      laparoscopic surgery, etc. Meanwhile, various strategies to improve the
      respectabilities are available, including neoadjuvant chemotherapy, portal vein
      embolization, two stage hepatectomy, and some locally ablative approaches. The
      current condition is difficult and sometimes confusing for a relevant surgeon
      when designing treatment protocols for more complex diseases. CONCLUSION: As the
      advancing of the management of liver metastases of colorectal cancer, more
      patients will become candidates for and benefit from potentially curative
      surgical resections. Optimal effect could only be achieved when used in a manner
      tailored to the individual patient.

PMID- 16580173
TI  - Molecular cytogenetics and allotetraploidy in the red vizcacha rat, Tympanoctomys
      barrerae (Rodentia, Octodontidae).
AB  - The theoretical impossibility of polyploidy in mammals was overturned by the
      discovery of tetraploidy in the red vizcacha rat, Tympanoctomys barrerae (2n =
      102). As a consequence of genome duplication, remarkably increased cell
      dimensions are observed in the spermatozoa and in different somatic cell lines of
      this species. Locus duplication had been previously demonstrated by in situ PCR
      and Southern blot analysis of single-copy genes. Here, we corroborate duplication
      of loci in multiple-copy (major rDNAs) and single-copy (Hoxc8) genes by
      fluorescence in situ hybridization. We also demonstrate that nucleolar dominance,
      a large-scale epigenetic silencing phenomenon characteristic of allopolyploids,
      explains the presence of only one Ag-NOR chromosome pair in T. barrerae.
      Nucleolar dominance, together with the chromosomal heteromorphism detected in the
      G-banding pattern and synaptonemal complexes of the species' diploid-like
      meiosis, consistently indicates allotetraploidy. Allotetraploidization can
      coherently explain the peculiarities of gene silencing, cell dimensions, and
      karyotypic features of T. barrerae that remain unexplained by assuming diploidy
      and a large genome size attained by the dispersion of repetitive sequences.

PMID- 16580174
TI  - Global exponential stability of impulsive high-order BAM neural networks with
      time-varying delays.
AB  - In this paper, global exponential stability and exponential convergence are
      studied for a class of impulsive high-order bidirectional associative memory
      (BAM) neural networks with time-varying delays. By employing linear matrix
      inequalities (LMIs) and differential inequalities with delays and impulses,
      several sufficient conditions are obtained for ensuring the system to be globally
      exponentially stable. Three illustrative examples are also given at the end of
      this paper to show the effectiveness of our results.

PMID- 16580175
TI  - Invariance priors for Bayesian feed-forward neural networks.
AB  - Neural networks (NN) are famous for their advantageous flexibility for problems
      when there is insufficient knowledge to set up a proper model. On the other hand,
      this flexibility can cause overfitting and can hamper the generalization of
      neural networks. Many approaches to regularizing NN have been suggested but most
      of them are based on ad hoc arguments. Employing the principle of transformation
      invariance, we derive a general prior in accordance with the Bayesian probability
      theory for feed-forward networks. An optimal network is determined by Bayesian
      model comparison, verifying the applicability of this approach. Additionally the
      prior presented affords cell pruning.

PMID- 16580176
TI  - Missing data imputation through GTM as a mixture of t-distributions.
AB  - The Generative Topographic Mapping (GTM) was originally conceived as a
      probabilistic alternative to the well-known, neural network-inspired, Self
      Organizing Maps. The GTM can also be interpreted as a constrained mixture of
      distribution models. In recent years, much attention has been directed towards
      Student t-distributions as an alternative to Gaussians in mixture models due to
      their robustness towards outliers. In this paper, the GTM is redefined as a
      constrained mixture of t-distributions: the t-GTM, and the Expectation
      Maximization algorithm that is used to fit the model to the data is modified to
      carry out missing data imputation. Several experiments show that the t-GTM
      successfully detects outliers, while minimizing their impact on the estimation of
      the model parameters. It is also shown that the t-GTM provides an overall more
      accurate imputation of missing values than the standard Gaussian GTM.

PMID- 16580178
TI  - Risk factors contributing to symptomatic plate removal following sagittal split
      osteotomy.
AB  - The records of 80 consecutive patients (160 plates) undergoing orthognathic
      surgery over a 2-year period were analysed to assess the percentage of plate
      removal from the mandible following sagittal split osteotomy. Factors considered
      in the study included age, sex, duration of operation, antibiotic prophylaxis
      regimen, general medical condition, smoking habits, mandibular moves, extraction
      of 3rd molars at time of surgery and the favourability of the mandibular splits.
      Infection was the sole reason for plate removal in this study. A removal rate of
      15.6% was noted. Age and duration of operation were the only 2 statistically
      significant factors to affect plate removal whilst some of the other factors
      showed increased odds ratios but were not statistically significant.

PMID- 16580177
TI  - Opposing effects of beta-arrestin1 and beta-arrestin2 on activation and
      degradation of Src induced by protease-activated receptor 1.
AB  - Protease-activated receptor 1 (PAR1), a G protein-coupled receptor for thrombin,
      is irreversibly proteolytically activated. beta-Arrestin1 and beta-arrestin2 have
      been reported to have different effects on signal desensitization and
      transduction of PAR1. In this study, we investigated whether beta-arrestin1 and
      beta-arrestin2 regulate Src-dependent activation of extracellular signal
      regulated kinases 1 and 2 (ERK1/2) induced by PAR1 in HEK 293 cells. Our results
      show that PAR1-mediated activation of Src and ERK1/2 in HEK 293 cells was
      increased with overexpression of beta-arrestin1 or depletion of beta-arrestin2.
      PAR1-mediated activation of Src and ERK1/2 in HEK 293 cells was decreased or
      eliminated with depletion of beta-arrestin1 or overexpression of beta-arrestin2.
      Furthermore, depletion of beta-arrestin2 blocked PAR1-induced degradation of Src.
      Thus, beta-arrestin1 and beta-arrestin2 have opposing roles in regulating the
      activation of Src induced by PAR1. beta-Arrestin2 also appears to promote PAR1
      induced degradation of Src. This degradation of Src provides a possible mechanism
      for terminating PAR1 signaling.

PMID- 16580179
TI  - Immunohistochemical expression of glucocorticoid and calcitonin receptors as a
      tool for selecting therapeutic approach in central giant cell granuloma of the
      jawbones.
AB  - Aggressive cases of central giant cell granuloma (CGCG) have been arbitrarily
      treated with steroids and calcitonin. The aim of this study was to develop a
      practical tool, based on the relative percentage of positively stained cells for
      glucocorticoid and/or calcitonin receptors, for selecting the appropriate
      therapeutic agents to treat CGCG. Forty-one formalin-fixed, paraffin-embedded
      blocks of CGCG were immunohistochemically stained for glucocorticoid and
      calcitonin receptors. Percentage of positive lesional mononuclear and giant cells
      was estimated for each case. Intense staining was considered as staining 50% or
      more of the cells. Correlations among staining scores were analysed by Spearman's
      test. All cases stained for glucocorticoid receptor. Heterogeneity among cases
      showed as intense staining in both cell types (21 lesions), in only one cell type
      (13 lesions) and weakly in both cell types (7 lesions). Only 23 cases
      demonstrated staining for calcitonin receptor, of which 15 stained intensely in
      both cell types and 7 in only one cell type. Among staining scores of both
      receptors, no significant statistical correlation was found (P>0.05). It can
      therefore be suggested that the relative percentage of immunohistochemically
      stained mononuclear and giant cells for glucocorticoid and/or calcitonin
      receptors can serve as a reliable and practical tool for selecting the
      appropriate therapeutic agent to treat CGCG. The clinical application of this
      method should be assessed in well controlled clinical studies, especially in
      cases of aggressive lesions, before initiating and during therapeutic treatment.

PMID- 16580180
TI  - The Schizotypic Syndrome Questionnaire (SSQ): Psychometrics, validation and
      norms.
AB  - This paper examines the psychometric properties (reliability and factor
      structure) and validity (relationship with various self-report measures and SPEM
      dysfunction) of the SSQ or Schizotypic Syndrome Questionnaire, a 108-item
      inventory for the measurement of 12 prodromal or schizotypic symptoms present in
      Van Kampen's model of schizophrenic prodromal unfolding. This paper also provides
      normative data for the SSQ. The SSQ demonstrates adequate reliability and breaks
      down into three correlated factors: negative schizotypy, asocial schizotypy and
      positive schizotypy. Results further attest the construct validity of the
      instrument. Because of the implications of the SSQ model for the definition of
      schizophrenia, the instrument's three-dimensional factor structure and the nature
      of one of the factors are discussed in more detail.

PMID- 16580181
TI  - Is rTMS efficient as a maintenance treatment for auditory verbal hallucinations?
      A case report.

PMID- 16580182
TI  - Two major 5'-untranslated regions for type XVII collagen mRNA.
AB  - BACKGROUND: Type XVII collagen is an important structural component of
      keratinocyte hemidesmosomes and its functional loss in genetic or autoimmune
      disease results in blistering of the skin. In neoplastic tissue aberrant
      expression is seen dependent on the stage of the tumor. While the sequence of the
      type XVII collagen encoding gene -COL17A1 - is now completely elucidated, the
      sequence of the 5'-untranslated region (UTR) of the mRNA is still unknown. Since
      UTRs can modulate translation efficiency, the determination of the UTR sequence
      is indispensable for understanding the regulation of translation of type XVII
      collagen mRNA. OBJECTIVE: To resolve the sequence of the 5'UTR of type XVII
      collagen mRNA and to analyse the promoter region for transcription motifs.
      METHODS: 5' Rapid amplification of cDNA ends (RACE) followed by sequence analysis
      and ribonuclease protection assays (RPA) were performed. RESULTS: RACE and
      sequence analysis revealed the presence of six different 5'UTRs for the type XVII
      collagen mRNA. The start points of these six transcripts differ but no
      alternative exons are used. The longest 5'UTR starts 220 nucleotides before the
      open reading frame, whereas the shortest UTR is only 89 nucleotides in length.
      RPA confirmed the RACE results and furthermore demonstrated that the 5'UTRs with
      lengths of 102 and 220 nucleotides are the two major transcripts. Transcription
      motif analysis of the 5' region of the COL17A gene demonstrated several binding
      sites for transcription factors including the Sp1 and activating protein-1 (AP-1)
      families. CONCLUSION: Type XVII collagen mRNA is alternatively transcribed, which
      may result in complex regulation of type XVII collagen.

PMID- 16580183
TI  - Pegylated tetraarylporphyrin entrapped in liposomal membranes. A possible novel
      drug-carrier system for photodynamic therapy.
AB  - A system of poly(ethylene glycol) bound tetraarylporphyrin entrapped in liposomal
      membranes was investigated. The interactions between the 5-(4
      hydroxymethylphenyl)-10,15,20-tritolylporphyrin (Po) covalently attached to the
      poly(ethylene glycol) chain (PEG-Po), and phosphatidylcholine liposomes in the
      aqueous solution were studied. The adsorption of the investigated polymer to
      lipid vesicles was confirmed by measurements of dynamic light scattering and zeta
      potential. Experimental results demonstrate that the diameter of liposomes
      increased and the absolute value of the zeta potential decreased after addition
      of PEG-Po. The binding constants (K(b)) of Po chromophores to liposome in pH
      range from 5.2 to 9.0 were determined using fluorescence spectroscopy. The degree
      of binding was found to be pH-independent and the average value was 24.6 +/- 0.9
      mg ml(-1). The acid-base properties of the porphyrin chromophores and their
      aggregation in an aqueous solution were also studied. pK values associated with
      imine-N protonation of the porphyrin core were found to be 2.59 and 0.68 at the
      ionic strength of 0.1 M. The equilibrium constant for dimerization, K(D), was
      found to be 5 x 10(3) M(-1).

PMID- 16580184
TI  - Scorpion digestive lipase: kinetic study using monomolecular film technique.
AB  - Using the classical emulsified system and the monomolecular film technique, we
      compared the interfacial properties of the scorpion digestive lipase (SDL) with
      those of higher animals'. In the absence of bile slats, SDL does not hydrolyse
      efficiently pure tributyrin, as well as dicaprin films maintained at low surface
      pressure. The preincubation of bile salts with tributyrin seems to be a better
      substrate for SDL than the pure tributyrin. A kinetic study on the surface
      pressure dependency, stereospecificity and regioselectivity of SDL was performed
      using monomolecular films of either three dicaprin isomers or three pairs of
      didecanoyl-deoxyamino-O-methyl glycerol enantiomers (DDG) containing a single
      hydrolysable decanoyl ester bond. With all diacylglycerol isomers, SDL has a
      surface pressure threshold of about 15 m Nm(-1), below which enzymatic activity
      is undetectable. SDL seems to prefer vicinal ester groups of the diacylglycerol
      isomers, with preference for sn-1 position at both 15 and 23 m Nm(-1).
      Furthermore, the maximum SDL activity is measured with DDG having a primary ester
      bond (1,3DDG, SII). This shows that SDL has a preference for the sn-1 position of
      this diacylglycerol analogue. Moreover, this was in line with the fact that SDL
      is inactive on sn-2 position of both DDG isomers and a triacylglycerol. With
      diacylglycerol analogue isomers, SDL shows a preference for distal isomers
      contrary to what has been observed with diacylglycerol isomers. SDL interacts
      with egg-phosphatidyl choline (egg-PC) monomolecular films. The critical surface
      pressure value (13 m Nm(-1)) is comparable to those of pancreatic lipases.

PMID- 16580185
TI  - Asthma and COPD.
AB  - The two obstructive airway diseases bronchial asthma and chronic obstructive
      pulmonary disease (COPD) represent major global causes of disability and death,
      and COPD is estimated to become the third most common cause of death by 2020. The
      structural and pathophysiologic findings in both diseases appear to be easily
      differentiated in the extremes of clinical presentation. However, a significant
      overlap may exist in individual patients regarding features such as airway wall
      thickening on computer tomography or reversibility and airway hyperresponsiveness
      in lung function tests. Airway inflammation differs between the two diseases. In
      bronchial asthma, airway inflammation is characterized in most cases by an
      increased number of activated T-lymphocytes, particularly CD4+ Th2 cells, and
      sometimes eosinophils and mast cells. The most notable difference of chronic
      severe asthma compared with mild to moderate asthma is an increased number of
      neutrophils. In stable COPD, airway inflammation is characterized by an increased
      number of T-lymphocytes, particularly CD8+ T cells, macrophages and neutrophils.
      With the progression of the disease severity, macrophage and neutrophil numbers
      increase. Although there may be a partial overlap between asthma and COPD in some
      patients, the differences in functional, structural and pharmacological features
      clearly demonstrate the consensus that asthma and COPD are different diseases
      along all their stages of severity.

PMID- 16580186
TI  - Antibiotic resistance of raw-milk-associated psychrotrophic bacteria.
AB  - The present study proposed to evaluate the breadth of antibiotic resistance among
      psychrotrophic bacteria spoiling raw milks in Finland. A core of 60 isolates,
      retrieved from farms, trucks, and silos, phenotypically characterized, were
      analysed with ATB PSE strips, composed of a panel of 17 beta-lactams and non-beta
      lactams antibiotics, representatives of five classes. Surprisingly, 60% of the
      psychrotrophs harboured multiresistant traits. We observed an increase of this
      feature along the cold chain of raw milk transportation.

PMID- 16580187
TI  - Structure and protective effect of exopolysaccharide from P. Agglomerans strain
      KFS-9 against UV radiation.
AB  - The water-soluble exopolysaccharide (WSEPS) from Pantoea agglomerans strain KFS-9
      isolated from mangrove forest was prepared by removing bacterial cell from the
      fermentation liquid following by concentration and cold ethanol precipitation of
      the supernatant. The polysaccharide material was purified by gel permeation
      chromatography on a Sephacryl S-300HR column and characterized using chemical and
      spectral methods. The results show that WSEPS is protein-bound polysaccharide,
      and it is composed of arabinose, glucose galactose and gulcuronic acid in the
      molar ratio of 1.0:2.2:2.8:0.9. Their antioxidant activities in vitro were
      studied by various antioxidant assays, including hydroxyl radical scavenging,
      superoxide radical scavenging and antilipid peroxidation. The results show that
      the WSEPS extracted had a high antioxidant activity in a concentration-dependent
      manner (except the activity of antilipid peroxidation). WSEPS quenched hydroxyl
      radicals, superoxide radicals at low amounts, the IC(50) of which were 0.07 and
      0.15 mg/ml, respectively. These results indicate that the protective effect of
      WSEPS against UV radiation is most likely to be due to the free radicals
      scavenging ability.

PMID- 16580188
TI  - Resistoflavine, cytotoxic compound from a marine actinomycete, Streptomyces
      chibaensis AUBN1/7.
AB  - In our systematic screening programme for marine actinomycetes, a bioactive
      Streptomycete was isolated from marine sediment samples of Bay of Bengal, India.
      The taxonomic studies indicated that the isolate belongs to Streptomyces
      chibaensis and it was designated as S. chibaensis AUBN1/7. The isolate yielded a
      cytotoxic compound. It was obtained by solvent extraction followed by the
      chromatographic purification. Based on the spectral data of the pure compound, it
      was identified as quinone-related antibiotic, resistoflavine (1). It showed a
      potent cytotoxic activity against cell lines viz. HMO2 (Gastric adenocarcinoma)
      and HePG2 (Hepatic carcinoma) in vitro and also exhibited weak antibacterial
      activities against Gram-positive and Gram-negative bacteria.

PMID- 16580189
TI  - Spirometry and smoking cessation advice in general practice: a randomised
      clinical trial.
AB  - RATIONALE: To assess the success rate of smoking cessation with the "minimal
      intervention strategy" in general practice, and to determine the influence of
      spirometry on this success rate. METHODS: Training in smoking cessation advice
      was given to 16 general practitioners (GPs). During 12 weeks, these GPs screened
      their practice population for smoking habits, the degree of dependence on
      nicotine, and the motivation to quit smoking. Patients willing to stop were
      randomised to a group that underwent a single office spirometry, or to a control
      group. The GPs were asked to support the attempts with the minimal intervention
      strategy. Success rates were compared after 6, 12 and 24 months. RESULTS: On a
      population of 5590 patients, 1206 smokers were identified (22%). To the
      vulnerable group, identified following the Prochaska and Di Clemente scheme, the
      proposal was made to change smoking behaviour. Two hundred and twenty-one
      patients undertook an attempt of smoking cessation. Nicotine replacement therapy
      (NRT) or bupropion was prescribed in 51% of the attempts. Sixty-four sustained
      quitters were counted after 6 months (29%), 43 after 1 year (19%) and 33 after 2
      years (15%). We found a small but statistically non-significant difference in
      success rate in favour of the group that underwent office spirometry. CONCLUSION:
      GPs can motivate almost 20% of their smoking population to quit smoking. The
      success rate with the minimal intervention strategy was 19% after 1 year and 15%
      after 2 years. We found no arguments in favour of confronting smokers with their
      lung function as a tool for enhancing smoking cessation.

PMID- 16580191
TI  - Water hyacinths as a resource in agriculture and energy production: a literature
      review.
AB  - Water hyacinths are becoming a problem in lakes, ponds and waterways in many
      parts of the world. This paper contains a literature study of different ways to
      use water hyacinths, mainly in agricultural or alternative energy systems. The
      literature review indicated that water hyacinths can be rich in nitrogen, up to
      3.2% of DM and have a C/N ratio around 15. The water hyacinth can be used as a
      substrate for compost or biogas production. The sludge from the biogas process
      contains almost all of the nutrients of the substrate and can be used as a
      fertiliser. The use of water hyacinth compost on different crops has resulted in
      improved yields. The high protein content makes the water hyacinth possible to
      use as fodder for cows, goats, sheep and chickens. Water hyacinth, due to its
      abundant growth and high concentrations of nutrients, has a great potential as
      fertiliser for the nutrient deficient soils of Africa and as feed for livestock.
      Applying the water hyacinths directly without any other processing than sun
      drying, seems to be the best alternative in small-scale use due to the relatively
      small losses of nutrients and workload required. To meet the ever-growing energy
      demand, biogas production could be one option but it requires investments and
      technological skills that would impose great problems in developing countries
      where the water hyacinth is often found. Composting as an alternative treatment
      has the advantage of a product that is easy to work into the soil compared with
      dried water hyacinths, because of the decomposed structure. Harvesting and
      transport of water hyacinths can be conducted manually on a small scale and does
      not require a new harvesting technique to be introduced. Transporting of fresh
      water hyacinths means, if used as fertiliser in amounts large enough to enhance
      or effect crop growth, an unreasonably large labour requirement. Based on the
      labour need and the limited access to technology, using dried water hyacinths, as
      green manure is a feasible alternative in many developing countries.

PMID- 16580190
TI  - A study of loculated tuberculous pleural effusions treated with intrapleural
      urokinase.
AB  - AIM: To assess the effect of intrapleural urokinase, vis-a-vis simple pleural
      drainage, on residual pleural thickening in a series of patients suffering from
      loculated tuberculous pleural effusion. PATIENTS AND METHOD: Twenty-nine patients
      (21 males and 8 females) with loculated pleural effusion were studied. These
      patients were randomly allocated to one of two groups: one group received
      intrapleural urokinase (n=12) and the other was treated by simple drainage with
      suction (n=17). The urokinase (125,000 UI) was administered into the pleural
      cavity via an intrathoracic tube. This procedure was repeated every 12h until the
      quantity of pleural fluid obtained was less than 50 cm3, at which point the
      intrathoracic tube was removed. RESULTS: In both groups, the biochemical analysis
      of the pleural fluid was an exudate and the fluid had a serous appearance.
      Pleural thickening when the drainage tube was removed was 8.09+/-3.36 mm for the
      group treated with urokinase, and 14.78+/-17.20mm (P>0.05) for the control group.
      Residual pleural thickening measured upon completion of medical treatment at 6
      months was 1.45+/-0.89 mm for the group treated with urokinase and 7.47+/-10.95
      mm for the control group (P<0.05). In the control group, only two patients
      presented over 10mm of residual pleural thickening. The mean quantity of fluid
      drained in the two groups was 1.487+/-711 ml for the patients with urokinase, and
      795+/-519 ml for the control group (P<0.01). CONCLUSION: Our study shows that
      patients with loculated tuberculous pleural effusion treated with urokinase
      suffered less from residual pleural thickening, as measured after six months,
      than those treated by simple drainage. It is therefore suggested that the
      administration of intrapleural urokinase is a safe and effective treatment for
      those patients who drain a larger quantity of pleural fluid.

PMID- 16580192
TI  - Defining the appropriate radiotherapy regimen for metastatic spinal cord
      compression in non-small cell lung cancer patients.
AB  - Many different schedules are used world wide for radiotherapy (RT) of metastatic
      spinal cord compression (MSCC). Non-small cell lung cancer (NSCLC) patients have
      an extraordinarily poor survival prognosis and would benefit from a short overall
      treatment time. This retrospective study compares short-course RT (1 x 8 Gy/1
      day, 5 x 4 Gy/1 week) and long-course RT (10 x 3 Gy/2 weeks, 15 x 2.5 Gy/3 weeks,
      20 x 2 Gy/4 weeks) for functional outcome in 252 NSCLC patients developing MSCC.
      Improvement of motor function occurred in 14% of patients, no change in 54%, and
      deterioration in 32%. Functional outcome was affected by the time of developing
      motor deficits before RT (>14 days better than 1-7 days and 8-14 days, P<0.001),
      not by the radiation regimen (P=0.87). In the short-course RT group, functional
      outcome was similar for 1 x 8 Gy and 5 x 4 Gy (P=0.94). Short-course and long
      course RT appear similarly effective for MSCC in NSCLC patients. As 1 x 8 Gy and
      5 x 4 Gy showed comparable results, 1 x 8 Gy can be considered appropriate.

PMID- 16580193
TI  - Effect of chitosan type on protein and water recovery efficiency from surimi wash
      water treated with chitosan-alginate complexes.
AB  - Previous research has shown that soluble protein recovery by chitosan (Chi)
      complexes with polyanions such as alginate (Alg) is more effective than using
      chitosan alone. In this study, Chi-Alg complexes were used to recover soluble
      proteins from surimi wash water (SWW) slightly acidified to pH 6. Six Chi samples
      differing in molecular weight (MW) and degree of deacetylation (DD) were used at
      20, 40 and 100mg/L SWW Chi-Alg complexes prepared with a Chi:Alg mixing ratio
      previously optimized (MR=0.2). FTIR analysis of the solids recovered revealed the
      three characteristic amide bands observed in the same region for untreated SWW
      confirming protein adsorption by Chi-Alg. The superior effectiveness of Chi
      complexes was confirmed but differences among chitosan types could not be
      correlated to MW and DD. Experimental Chi samples with 94%, 93%, 75% and 93% DD
      and 22, 47, 225 and 3404 x 10(3)Da, respectively, showed 73-76% protein
      adsorption while a commercial chitosan sample with 84% DD and 3832 x 10(3)Da had
      74-83% protein adsorption. An experimental chitosan, SY-1000 with 94% DD and 1.5
      x 10(6)Da, showed the highest protein adsorption (79-86%) and turbidity reduction
      (85-92%) when used at 20mg/L SWW.

PMID- 16580194
TI  - Characterization of poly(3-hydroxybutyrate) produced by Cupriavidus necator in
      solid-state fermentation.
AB  - Solid-state fermentation (SSF) has recently been proposed as an alternative to
      submerged fermentation for the production of poly(hydroxyalkanoates). In the
      present work, X-ray diffraction, differential scanning calorimetry, nuclear
      magnetic resonance and infrared spectroscopy were employed to investigate the
      chemical structure, as well as the thermal properties and the crystalline
      morphology of poly(3-hydroxybutyrate) samples produced by SSF, using as raw
      material either soy cake or soy cake supplemented with 2.5% (m/m) sugarcane
      molasses. The results obtained showed that the biopolymer obtained by SSF
      presented the same properties as commercial PHB, except for the higher molar mass
      and the lower degree of crystallinity that were observed. Thus, the present data
      indicate that solid-state fermentation is an interesting alternative for the
      production of PHB, allowing the production of biopolymers with adequate
      properties from low-cost, renewable resources.

PMID- 16580195
TI  - Composted municipal waste effects on chemical properties of a Brazilian soil.
AB  - The spread of composted municipal waste (CMW) on land can be used for sustainable
      crop production. Nevertheless, heavy metals availability may be a problem.
      Therefore, the main objective of this study was to assess the impact of CMW
      disposal on heavy metal accumulation in soil and plants. The treatments consisted
      of an untreated plot (control) and four rates of CMW application. All plots were
      cultivated in succession of carrot, cauliflower, sweet corn, and radish. Cu and
      Pb significantly accumulated in the topsoil (0-5 cm) with a similar pattern in
      the depths of 5-10 cm and 10-20 cm. Cauliflower, for Fe and Cu, and radish, for
      Pb and Cu, had their tissue analysis significantly affected due to the increasing
      rates of application of CMW. Nevertheless, the levels of accumulation in both,
      soil and plant, are within permissible limits. The evidences provided by this
      experiment indicated that heavy metals are less likely to cause problems for the
      estimation of CMW loadings to Brazilian agricultural land.

PMID- 16580196
TI  - Comparative studies on the adsorption of Cr(VI) ions on to various sorbents.
AB  - The adsorption of Cr(VI) ions onto various sorbents (chitin, chitosan, ion
      exchangers; Purolite CT-275 (Purolite I), Purolite MN-500 (Purolite II) and
      Amberlite XAD-7) was investigated. Batch adsorption experiments were carried out
      as a function of pH, agitation period and concentration of Cr(VI) ions. The
      optimum pH for Cr(VI) adsorption was found as 3.0 for chitin and chitosan. The
      Cr(VI) uptake by ion exchangers was not very sensitive to changes in the pH of
      the adsorption medium. The maximum chromium sorption occurred at approximately 50
      min for chitin, 40 min for Purolite II and 30 min for chitosan, Purolite I and
      Amberlite XAD-7. The suitability of the Freundlich and Langmuir adsorption models
      were also investigated for each chromium-sorbent system. Adsorption isothermal
      data could be accurately interpreted by the Langmuir equation for chitosan,
      chitin, Purolite I and Purolite II and by the Freundlich equation for chitosan,
      chitin and Amberlite XAD-7. The chromium(VI) ions could be removed from the
      sorbents rapidly by treatment with an aqueous EDTA solution and at the same time
      the sorbent regenerated and also could be used again to adsorb by heavy metal
      ions. The results showed that, chitosan, which is a readily available, economic
      sorbent, was found suitable for removing chromium from aqueous solution.

PMID- 16580197
TI  - Biodiesel production using a membrane reactor.
AB  - The immiscibility of canola oil in methanol provides a mass-transfer challenge in
      the early stages of the transesterification of canola oil in the production of
      fatty acid methyl esters (FAME or biodiesel). To overcome or rather, exploit this
      situation, a two-phase membrane reactor was developed to produce FAME from canola
      oil and methanol. The transesterification of canola oil was performed via both
      acid- or base-catalysis. Runs were performed in the membrane reactor in semi
      batch mode at 60, 65 and 70 degrees C and at different catalyst concentrations
      and feed flow rates. Increases in temperature, catalyst concentration and
      feedstock (methanol/oil) flow rate significantly increased the conversion of oil
      to biodiesel. The novel reactor enabled the separation of reaction products
      (FAME/glycerol in methanol) from the original canola oil feed. The two-phase
      membrane reactor was particularly useful in removing unreacted canola oil from
      the FAME product yielding high purity biodiesel and shifting the reaction
      equilibrium to the product side.

PMID- 16580198
TI  - Potential for hydrogen and methane production from biomass residues in Canada.
AB  - Canada generates approximately 1.45 x 10(8)t of residual biomass per year,
      containing an estimated energy value of 2.28 x 10(9)GJ, which is equivalent to
      about 22% of Canada's current annual energy use. Anaerobic digestion of these
      biomass residues using conventional technologies could generate 1.14 x
      10(10)m(3)/year of CH(4) with a heating value of 4.56 x 10(8)GJ. Conversion of
      these residues using emerging technologies that favor the synthesis of H(2) and
      represses the synthesis of CH(4) could generate 1.47 x 10(10)m(3)/year renewable
      H(2), with a heating value of 1.89 x 10(8)GJ. While CH(4)-production results in a
      larger amount of energy recovery, generating H(2) from waste biomass is a
      renewable alternative that could fuel the hydrogen economy. Additional research
      to further both the technical and commercial development of microbial bio-energy
      from biomass is warranted.

PMID- 16580199
TI  - Identification of 2-acylaminothiophene-3-carboxamides as potent inhibitors of
      FLT3.
AB  - A series of 2-acylaminothiophene-3-carboxamides has been identified which exhibit
      potent inhibitory activity against the FLT3 tyrosine kinase. Compound 44 inhibits
      the isolated enzyme (IC50 = 0.027 microM) and blocks the proliferation of MV4-11
      cells (IC50 = 0.41 microM). Structure-activity relationship studies within this
      series are described in the context of a proposed binding model within the ATP
      binding site of the enzyme.

PMID- 16580200
TI  - Protein tyrosine phosphatase 1B inhibitory activity of triterpenes isolated from
      Astilbe koreana.
AB  - Bioassay-guided fractionation of a MeOH extract of the rhizomes of Astilbe
      koreana (Saxifragaceae), using an in vitro protein tyrosine phosphatase 1B
      (PTP1B) inhibitory assay, resulted in the isolation of a new triterpene,
      3alpha,24-dihydroxyolean-12-en-27-oic acid (4), along with four triterpenes, 3
      oxoolean-12-en-27-oic acid (1), 3beta-hydroxyolean-12-en-27-oic acid (beta
      peltoboykinolic acid; 2), 3beta-hydroxyurs-12-en-27-oic acid (3), and 3beta,6beta
      dihydroxyolean-12-en-27-oic acid (astilbic acid; 5). Compounds 1-5 inhibited
      PTP1B with IC50 values of 6.8+/-0.5, 5.2+/-0.5, 4.9+/-0.4, 11.7+/-0.9, and 12.8+/
      1.1 microM, respectively. Our results indicate that 3-hydroxyl group and a
      carboxyl group in this type of triterpenes may be required for the activity,
      while addition of one more hydroxyl group at C-6 or C-24 may be responsible for a
      loss of activity. Thus, compounds 2 and 3 which possess only one hydroxyl group
      at C-3 and a carboxyl group at C-27 could be potential PTP1B inhibitors.

PMID- 16580201
TI  - Diarylacetylene piperidinyl amides as novel anxiolytics.
AB  - N-Phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4-piperidine]acetamide (9) and
      related piperidine acetamide derivatives have good oral activity in the elevated
      plus maze, an animal model predictive of clinical efficacy for the treatment of
      anxiety. Modest affinity was observed for the neurokinin NK-1 and 2 receptors,
      which are known to be involved in the regulation of mood and emotion.

PMID- 16580202
TI  - Discovery of SB-705498: a potent, selective and orally bioavailable TRPV1
      antagonist suitable for clinical development.
AB  - Small molecule antagonists of the vanilloid receptor TRPV1 (also known as VR1)
      are disclosed. Pyrrolidinyl ureas such as 8 and 15 (SB-705498) emerged as lead
      compounds following optimisation of the previously described urea SB-452533.
      Pharmacological studies using electrophysiological and FLIPR-Ca2+-based assays
      showed that compounds such as 8 and 15 were potent antagonists versus the
      multiple chemical and physical modes of TRPV1 activation (namely capsaicin, acid
      and noxious heat). Furthermore, 15 possessed suitable developability properties
      to enable progression of this compound into in vivo studies and subsequently
      clinical development.

PMID- 16580203
TI  - Rediscovery of natural products using genomic tools.
AB  - A screening methodology called 'genomic screening' was established to identify
      natural products that can regulate cellular gene expression. Application of
      genomic screening to Keishi-bukuryo-gan (KBG), a Japanese herbal medicine
      formulation, identified a previously unnoticed transcriptional effect by linoleic
      acid, a known KBG component. The approach opens up a possibility to develop cell
      permeable molecular tools for functional genomics research and sets a stage to
      evaluate the potential of natural products for transcription therapies.

PMID- 16580204
TI  - Stilbene-based anticancer agents: resveratrol analogues active toward HL60
      leukemic cells with a non-specific phase mechanism.
AB  - Several stilbenes, related to known resveratrol, have been synthesized and tested
      for their anticancer effect on HL60 leukemia cell line, taking particular care of
      the cell cycle analysis. The most potent compound was the known (Z)-3,4',5
      trimethoxystilbene (6b) which was active as apoptotic agent at 0.24 microM.
      Differently from other stilbenes (including resveratrol) that induced a prevalent
      recruitment of cells in S phase of cell cycle, we found a peculiar behavior of 6b
      that caused a decrease of cells in all phases of cell cycle (G0-G1, S, and G2-M)
      and a proportional increase of apoptotic cells. The potent pro-apoptotic activity
      shown by compound 6b and its effects on cell cycle make this compound of great
      interest for further investigations.

PMID- 16580206
TI  - Two-week rule: has prioritisation of breast referrals by general practitioners
      improved?
AB  - INTRODUCTION: A 9-month audit, soon after the introduction of the 2-week rule in
      the UK in 1999, showed that a significant number of breast cancer patients were
      referred as non-urgent by their GPs, when the goal is that all suspected breast
      cancer patients should be seen by a hospital specialist urgently within 2 weeks
      of referral. The aim of this study was to determine whether GP grading of
      referrals into urgent and non-urgent had improved. METHOD: A retrospective review
      of GP referrals over 8 months, between September 2003 and April 2004, with regard
      to their urgency, subsequent diagnosis and the use of proformas (standardised
      referral formats) was carried out. The results were compared to the 1999 audit.
      RESULTS: Eighty-two of 1178 patients referred by GP had breast cancer, versus 115
      of 1176 patients referred in 1999. Sixty-eight per cent (56/82) of breast cancer
      patients were referred as urgent, compared to 47% (54/115) in 1999 (P=0.005). A
      proforma was used in 47% (548/1178) of GP referrals while no proforma was used in
      1999. Sixty-five of the 82 cancer patients were referred with a proforma and 85%
      (55/65) were referred as urgent. CONCLUSION: GP prioritisation of referrals has
      improved since 1999. With the use of proformas a significant number of patients
      with cancer were referred urgently.

PMID- 16580205
TI  - 2,5-Disubstituted pyrrolidine carboxylates as potent, orally active sphingosine-1
      phosphate (S1P) receptor agonists.
AB  - A series of 2,5-cis-disubstituted pyrrolidines were synthesized and evaluated as
      S1P receptor agonists. Compounds 15-21 were identified with good selectivity over
      S1P3 which lowered circulating lymphocytes after oral administration in mice.

PMID- 16580207
TI  - New insights into the control of mRNA decapping.
AB  - mRNA decapping irreversibly targets mRNAs for fast decay. Cap removal is
      catalyzed by decapping protein Dcp2 but also requires Dcp1. Recently, two groups
      have provided a first glimpse of the regulation mechanism of this crucial step in
      gene expression. Resolution of the yeast Dcp2 structure has enabled
      identification of the residues that are important for its interaction with Dcp1.
      However, the human decapping machinery seems to be more complex because a third
      component, Hedls, is required for a functional Dcp1-Dcp2 interaction.

PMID- 16580208
TI  - Antagonists of the myelin-associated glycoprotein: a new class of tetrasaccharide
      mimics.
AB  - The tetrasaccharide substructure 1 of the ganglioside GQ1balpha shows a
      remarkable affinity for the myelin-associated glycoprotein (MAG). In the search
      for structurally simplified and pharmacokinetically improved mimics of 1,
      biphenyl was identified as a feasible replacement for the core disaccharide
      Galbeta(1-3)GalNAc according to saturation transfer difference (STD) NMR and
      molecular modeling investigations. Using Suzuki coupling, a convergent synthesis
      of the mimics was achieved. To optimize the yields of the coupling reactions, the
      catalytic effects of microwave irradiation and conventional heating were
      compared. The biological evaluation of mimics 3 and 4 was performed in a
      competitive target-based assay. It was found that the relative inhibitory potency
      (rIP) of antagonist 3 was clearly enhanced in comparison to the reference
      trisaccharide 2, despite the former having a much simpler structure. In addition
      to the improved synthetic feasibility, an increase of the partition coefficient
      between octanol and water (logP), and therefore a beneficial change in the
      pharmacokinetic properties of 3 and 4 was achieved.

PMID- 16580209
TI  - Nonsteroidal progesterone receptor ligands (II); synthesis and SAR of new
      tetrahydrobenzindolone derivatives.
AB  - The human progesterone receptor (PR) binding affinity and the PR agonistic or
      antagonistic potency of tetrahydronaphthofuranone derivatives were shown
      previously to be markedly influenced by substituents at the 6- and 7-positions.
      Here, we synthesized tetrahydrobenzindolones possessing a lactam ring, which
      enabled us to modify the 6- and 7-positions more freely, since
      tetrahydrobenzindolones are chemically more stable than
      tetrahydronaphthofuranones. The tetrahydrobenzindolone derivatives generally
      showed higher PR binding affinity than the corresponding
      tetrahydronaphthofuranones. We also succeeded in separating the agonistic and
      antagonistic activities by choosing suitable substituent groups at the 6- and/or
      7-position(s) of the tetrahydrobenzindolone. The effects of representative
      agonists, 12c (CP8668), and 14a (CP8816), and a representative antagonist, 15f
      (CP8661), were confirmed in in vivo tests. In this report, we mainly describe the
      synthesis and structure-activity relationships (SAR) of tetrahydrobenzindolone
      derivatives, as new nonsteroidal PR ligands.

PMID- 16580210
TI  - Discovery of thiochroman and chroman derivatives as pure antiestrogens and their
      structure-activity relationship.
AB  - In order to develop pure antiestrogens, a series of 7-hydroxy-3-(4-hydroxyphenyl)
      3-methylchroman and 7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman derivatives
      with sulfoxide containing side chains at the 4-position were designed,
      synthesized, and evaluated. Among them, compounds 14b and 24b functioned as pure
      antiestrogens with the ability to downregulate ER, and their in vitro and in vivo
      antiestrogen activities were similar to those of ICI182,780. In addition, the
      structure-activity relationship indicated that the (3RS,4RS)-configuration
      between the 3- and 4-position, the methyl group at the 3-position, the 9
      methylene chain between the scaffold and the sulfoxide moiety, and the terminal
      perfluoroalkyl moiety play an important role in increasing estrogen receptor
      binding and oral antiestrogen activities.

PMID- 16580211
TI  - QSAR study of 1,4-dihydropyridine calcium channel antagonists based on gene
      expression programming.
AB  - The gene expression programming, a novel machine learning algorithm, is used to
      develop quantitative model as a potential screening mechanism for a series of 1,4
      dihydropyridine calcium channel antagonists for the first time. The heuristic
      method was used to search the descriptor space and select the descriptors
      responsible for activity. A nonlinear, six-descriptor model based on gene
      expression programming with mean-square errors 0.19 was set up with a predicted
      correlation coefficient (R2) 0.92. This paper provides a new and effective method
      for drug design and screening.

PMID- 16580212
TI  - Novel potent and selective calcium-release-activated calcium (CRAC) channel
      inhibitors. Part 1: synthesis and inhibitory activity of 5-(1-methyl-3
      trifluoromethyl-1H-pyrazol-5-yl)-2-thiophenecarboxamides.
AB  - We synthesized and evaluated a series of 5-(1-methyl-3-trifluoromethyl-1H-pyrazol
      5-yl)-2-thiophenecarboxamides to identify potent inhibitors of calcium-release
      activated calcium (CRAC) channels with greater selectivity than voltage-operated
      calcium (VOC) channels. These efforts resulted in identification of compounds 22
      and 24. The former exhibits highly potent and selective CRAC channel inhibitory
      activity, and the latter inhibited phytohemagglutinin-induced interleukin-2
      production by Jurkat T lymphocytes and concanavalin A-induced hepatitis in mice.

PMID- 16580213
TI  - Nonsteroidal progesterone receptor ligands (I): synthesis and SAR of new
      tetrahydronaphthofuranone derivatives.
AB  - We have synthesized a series of nonsteroidal progesterone receptor (PR) ligands,
      tetrahydronaphthofuranones, structurally based on the fungal metabolite PF1092C.
      Structure-activity relationship studies revealed that substituents at the 6- and
      7-positions were critical for PR binding affinity and for agonist or antagonist
      activity. Compounds in this series, exemplified by 19i, exhibited high affinity
      and high specificity for PR over other steroid hormone receptors and acted as
      selective PR antagonists. Further modification of PF1092C may generate compounds
      of potential pharmacological interest.

PMID- 16580214
TI  - Cytoprotective effect of caffeic acid phenethyl ester (CAPE) and catechol ring
      fluorinated CAPE derivatives against menadione-induced oxidative stress in human
      endothelial cells.
AB  - Caffeic acid phenethyl ester (CAPE), a natural polyphenolic compound with many
      biological activities, has been shown to be protective against ischemia
      reperfusion injury. We have synthesized six new catechol ring-fluorinated CAPE
      derivatives and evaluated their cytotoxic and cytoprotective effects against
      menadione-induced cytotoxicity in human umbilical vein endothelial cells. These
      results provide some insights into the structural basis of CAPE cytoprotection in
      this assay, which does not appear to be based solely on direct antioxidant
      properties.

PMID- 16580215
TI  - Nuclear decay data: observations and reflections.
AB  - Decay data constitute an important feature of nuclear physics that plays a
      significant role in the various work programmes of members and associates of the
      International Committee for Radionuclide Metrology (ICRM). At the invitation of
      the ICRM, a review has been undertaken with the joint aims of emphasising decay
      data achievements over the previous 10 years, and highlighting inadequacies that
      remain to be addressed in the future.

PMID- 16580216
TI  - Standardization of 18F by coincidence and LSC methods.
AB  - The nuclide 18F disintegrates to 18O by beta+ emission (96.86%) and electron
      capture (3.14%) with a half-life of 1.8288 h. It is widely used in nuclear
      medicine for positron emission tomography (PET). A radioactive solution of this
      nuclide has been standardized by two techniques: coincidence measurements with a
      pressurized proportional counter and liquid scintillation counting using the
      CIEMAT/NIST method. One ampoule containing a solution calibrated in activity was
      sent for measurement at the International Reference System maintained by the
      BIPM. Results are in excellent agreement with SIR values.

PMID- 16580217
TI  - Radon activity concentration--a Euromet and BIPM supplementary comparison.
AB  - For the first time, a comparison of radon activity concentration in air has been
      performed within the scope of Euromet. In the project 657, 'Comparison of
      calibration facilities for the radon activity concentration,' 12 participants
      from 9 countries compared different radon reference atmospheres at 1, 3 and 10 k
      Bq m-3 via a transfer standard. The comparison was listed as BIPM supplementary
      comparison EUROMET.RI(II)-S1. The results of most participants are correlated due
      to common traceability to one single radon gas standard producer. This makes a
      careful correlation analysis necessary to achieve an appropriate comparison
      reference value. The results of the comparison as well as the complex analysis of
      the correlated set of data is presented and discussed.

PMID- 16580219
TI  - Half-life measurement of 55Fe.
AB  - The half-life of 55Fe was determined experimentally and compared with literature
      values. A solid 55Fe source was prepared by electrodeposition and repeatedly
      measured in an X-ray detector at a constant, low solid angle. In total, more than
      six hundred measurements were performed over a period of ten months,
      corresponding to one third of the half-life. The experimental method and the
      corresponding uncertainty budget are presented. The result of 1005.2+/-1.4 days
      is slightly higher than the current recommended values.

PMID- 16580218
TI  - Cascade summing effects in close geometry gamma-ray spectrometry.
AB  - Low-level gamma-ray spectrometry, particularly in underground laboratories, is
      used to measure radioactivity in diverse close geometries, often placing samples
      directly on the detector which favours strong cascade summing effects. Monte
      Carlo modelling of the efficiency is extended to cascade summing effects from
      complete decay sequences including positron emitting radionuclides. The effect of
      geometrical uncertainties on the overall uncertainty is presented. The results
      reinforce the need for radiography of the detector and inclusion of the detector
      shielding in the model.

PMID- 16580220
TI  - Estimation of trace elements in some anti-diabetic medicinal plants using PIXE
      technique.
AB  - Trace elemental analysis was carried out in various parts of some anti-diabetic
      medicinal plants using PIXE technique. A 3MeV proton beam was used to excite the
      samples. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, Br, Rb and Sr were
      identified and their concentrations were estimated. The results of the present
      study provide justification for the usage of these medicinal plants in the
      treatment of diabetes mellitus (DM) since they are found to contain appreciable
      amounts of the elements K, Ca, Cr, Mn, Cu, and Zn, which are responsible for
      potentiating insulin action. Our results show that the analyzed medicinal plants
      can be considered as potential sources for providing a reasonable amount of the
      required elements other than diet to the patients of DM. Moreover, these results
      can be used to set new standards for prescribing the dosage of the herbal drugs
      prepared from these plant materials.

PMID- 16580221
TI  - Determination of the intensity of X- and gamma-ray emissions in the decay of
      153Sm.
AB  - The activity of a 153Sm solution was determined by means of liquid scintillation
      counting and an ionization chamber. Several accurately calibrated X- and gamma
      ray spectrometers were used to measure point sources. The use of different
      detectors results in improvements to the accuracy of the data around 100 keV
      where the efficiency curve changes significantly. Photon emission intensities
      have been derived for the main X- and gamma-rays, and the 103-keV emission has a
      measured intensity of (29.07 (20)) per 100 disintegrations.

PMID- 16580222
TI  - Standardization of radionuclide by beta(LS)-gamma coincidence counting using the
      geometry-efficiency variation method.
AB  - A liquid scintillation counting method consisting of three photomultiplier tubes
      for beta counters and a NaI(Tl) gamma counter has been developed for the
      standardization of radionuclides with the beta-gamma coincidence technique. The
      beta detection efficiency functions are obtained by means of a geometry-variation
      method developed in the present work; an array of beta detectors is moved
      uniformly at the same time from a centrally located counting vial to 50 mm. The
      method has been applied in the standardization of 60Co and 134Cs. Unquenched
      liquid scintillation samples with nominal count rates from 1000 to 6000 s-1 were
      prepared. The observed beta detection efficiencies with this method are from 90
      to 45% in the case of 60Co, and from 84 to 50% for 134Cs. The output of each beta
      channel is summed together and compared with gamma data by the coincidence
      analyzer. The dead time of each counting channel is adjusted to be 20 micros,
      sufficiently long to suppress the afterpulses in the beta counting channel. The
      activity of each sample is determined by using the Cox and Isham formula. The
      obtained results are in good agreement with KRISS certified values.

PMID- 16580223
TI  - Neohormone systems as exciting targets for drug development.

PMID- 16580225
TI  - Expression of tumor necrosis factor alpha and its receptors during cellular
      differentiation.
AB  - Tumor necrosis factor alpha (TNFalpha) is a potent proinflammatory cytokine also
      involved in cellular differentiation processes. TNFalpha and both of its
      receptors (TNFR1 and TNFR2) can be co-expressed on the same cell, allowing for
      local signaling. This study has examined the expression of all components
      necessary for autocrine cytokine regulation during human hematopoietic,
      epithelial, and mesenchymal models of cellular differentiation. Macrophage and
      dendritic differentiation of human peripheral blood monocytes decreased their
      TNFalpha and TNFR2 expression while increasing the TNFR1 mRNA. In colon
      epithelial cell lines (HT-29 and Caco-2) TNFalpha-, TNFR1-, and TNFR2-expression
      was decreased upon differentiation. No changes, however, were seen during human
      skin keratinocyte differentiation. TNFR1 expression was unchanged in all three
      mesenchymal lineages (adipogenesis, chondrogenesis, osteogenesis) tested.
      Differentiation decreases the TNFalpha message in adipocytes and the TNFR2 mRNA
      in adipocytes and osteocytes. Our results demonstrate that there is no general
      principle for TNFalpha signaling during conversion of cells from progenitor to a
      more differentiated phenotype. Paracrine signaling by TNFalpha to orchestrate
      different cell types during tissue development and remodeling, therefore,
      probably overrides the autocrine regulation of differentiation by TNFalpha. Non
      signaling TNF-receptors may protect chondrocytes and osteocytes from the anti
      differentiation effects of local TNFalpha production.

PMID- 16580224
TI  - Studying non-mammalian models? Not a fool's ERRand!
AB  - Through studies in mammalian model systems, the estrogen-receptor-related
      receptor (ERR) alpha, an orphan nuclear receptor, has been shown to interfere
      with estrogen signaling and might therefore be an interesting pharmaceutical
      target in estrogen-related diseases. ERRalpha is also involved in energy storage
      and consumption, and its modulation might be of relevance in the treatment of
      obesity and diabetes. Recent data have also been published on the effects of this
      receptor, as well as other members of the ERR family, in non-mammalian animal
      model systems. Besides indications concerning their mechanisms of action, this
      analysis demonstrated a role for ERRalpha in controlling cellular movements, and
      suggested that ERRs might be implicated in a more subtle range of processes than
      originally envisioned.

PMID- 16580227
TI  - Isolation of esterified fatty acids bound to serum albumin purified from human
      plasma and characterised by MALDI mass spectrometry.
AB  - Human serum albumin (HSA) is the most abundant protein in plasma. It is known to
      transport drugs as well as endogenous ligands, like free fatty acids (FFA). A
      mass spectrometry based method was applied to analyze the albumin bound lipid
      ligands. HSA was isolated from a human plasma pool by cold ethanol fractionation
      and ion exchange chromatography. HSA was defatted using a solvent extraction
      method to release the copurified lipids bound to the protein. The extracts were
      then analyzed by matrix-assisted laser desorption ionisation (MALDI) mass
      spectrometry (MS). Using this method, phospholipids and acylglycerols were
      detected. The phospholipids were identified to be lyso-phosphatidylcholine (lyso
      PC) with distribution of different fatty acids (palmitic, stearic, oleic, and
      linoleic acids). An abundant species in the HSA lipid extract was found to be a
      diacylglycerol, composed of two linoleic and/or oleic acid chains. The identified
      motifs reflect structures that are known to be present in plasma. The binding of
      lysophospholipids has already been described but it is the first ever-reported
      evidence of native diacylglycerol ligands bound to HSA. Besides the native
      ligands from plasma a triacylglycerol was detected that has been added during the
      albumin preparation steps.

PMID- 16580226
TI  - The cytokine balance in the maintenance of a persistent infection with Salmonella
      enterica serovar Typhimurium in mice.
AB  - ClpXP, serine protease-disrupted mutant of Salmonella enterica serovar
      Typhimurium chi3306 exhibits attenuated but persistent infection in mice. During
      infection with S. enterica serovar Typhimurium ClpXP-disrupted mutant, gamma
      interferon (IFN-gamma) produced by CD4+ cells was up-regulated on day 10 and
      tumor necrosis factor-alpha (TNF-alpha) produced by CD8+ cells was up-regulated
      on day 30 after infection. Treatment of monoclonal antibodies against cytokines
      showed that IFN-gamma and interleukin 10 (IL-10) were involved in maintenance of
      growth of S. Typhimurium mutant on day 10 after infection, and IFN-gamma, TNF
      alpha and transforming growth factor-beta (TGF-beta) were involved in maintenance
      of growth of this bacterium on day 30 after infection. During persistent
      infection of S. Typhimurium mutant, IFN-gamma, TNF-alpha, IL-10 and TGF-beta may
      play different roles to maintain the persistent infection. The cytokine balance
      might be important in persistent infection with ClpXP-disrupted S. enterica
      serovar Typhimurium.

PMID- 16580228
TI  - Validation of a computer software program for statistical analysis of accelerated
      stability studies on biological standards.
AB  - Long-term stability is an essential requirement for biological measurement
      standards and it has been evaluated by applying the Arrhenius model to the data
      obtained from accelerated thermostability studies. A computer program DEGTEST
      suited to a mainframe computer has been used for evaluating the stability of
      biological standards for more than a decade. This paper describes the validation
      of a computer program executable in a personal computer Microsoft Windows XP
      environment for the analysis of accelerated thermostability study data.

PMID- 16580229
TI  - A strategy for identifying serodiagnostically relevant antigens of Leishmania or
      other pathogens in genetic libraries.
AB  - Different individuals, when infected with the same parasite, rarely produce
      antibodies against the same set of antigens. Indeed, unless a particular antigen
      happens to be recognized by antibodies in all individuals, the use of a single
      antigen in the serodiagnosis of parasitic diseases leads, invariably, to false
      negative results. A straightforward method for pin-pointing, in genetic
      libraries, the precise antigens that would increase serodiagnostic assay
      sensitivities is presented. The method is based on the utilization of sera that
      produced false-negative results against previously available antigens. Employing
      this false-negative serum-selection methodology for the identification of new
      Leishmania infantum recombinant antigens (rAgs), the sensitivity of a dipstick
      assay for anti-Leishmania antibodies in a panel of sera from patients with
      visceral leishmaniasis was increased from 83.3% to 98.1%, without affecting its
      specificity, by the inclusion of a fifth and a sixth L. infantum rAg.

PMID- 16580231
TI  - A genetic perspective on the geographic association of taxa among arid North
      American lizards of the Sceloporus magister complex (Squamata: Iguanidae:
      Phrynosomatinae).

PMID- 16580230
TI  - Development of recombinant chicken IgY from single chain fragment of variable
      region for diagnosis of BSE.
AB  - We generated two recombinant chicken IgYs, designated Ab3-15 and Ab4-19, against
      mammalian prion protein (PrP) from the single chain fragment of variable region
      (scFv) antibodies. These two antibodies recognized PrP(Sc) from bovine spongiform
      encephalopathy (BSE) in cattle and were more sensitive than the corresponding
      scFv antibodies. These antibodies also recognized PrP(Sc) from other scrapie
      infected mammals. These results indicate that Ab3-15 and Ab4-19 are useful for
      diagnosis of BSE as well as other prion diseases.

PMID- 16580232
TI  - Histochemical assessment of early myocardial infarction using 2,3,5
      triphenyltetrazolium chloride in blood-perfused porcine hearts.
AB  - INTRODUCTION: Although the chemical mechanism of the triphenyltetrazolium (TTC)
      reaction, for macroscopic detection of myocardial infarction, has been described
      previously, literature reports on correct tissue preparation and the use of this
      technique in intact large animals are lacking. METHODS: We investigated the
      special requirements for TTC staining in blood-perfused porcine hearts, validated
      the various handling steps and provided detailed information for precise and easy
      use of this histochemical method. The left anterior descending coronary artery
      was occluded for 45 min followed by 6 h of reperfusion in an open chest
      preparation using anesthetised domestic pigs. The hearts were excised and the
      organ-handling steps and TTC-staining procedure validated. RESULTS: The protocol
      includes (i) intracoronary saline perfusion, (ii) pressure-controlled
      determination of the non-ischemic region by Evans blue dye, (iii) a freeze-thaw
      cycle, (iv) a triphenyltetrazolium incubation period, and (v) a bleach cycle with
      4% paraformaldehyde. The TTC-staining results were confirmed by histology of
      transitional regions of the infarct area, area-at-risk and non-risk-region.
      DISCUSSION: If some special features associated with blood-perfused porcine
      hearts are considered carefully, reliable results for subsequent infarct size
      calculations can be obtained and large potential errors excluded.

PMID- 16580233
TI  - Adenylyl cyclase signaling mechanisms of relaxin and insulin action: similarities
      and differences.
AB  - The adenylyl cyclase signaling mechanism (ACSM) of relaxin H2 action was
      discovered and deciphered in mammalian muscles. A study of signaling blocks
      involved in ACSM of relaxin in comparison with that of insulin previously
      detected showed a close similarity throughout the post-receptor signaling chain
      of both hormones. The inhibitory action of tyrosine kinase blockers on the
      hormone AC activating effect indicates that the relaxin receptor involved in ACSM
      is likely to be of the tyrosine kinase type. However, a recent discovery of a
      relaxin receptor with serpentine architecture leaves open the question concerning
      the existence of receptor of the tyrosine kinase type. The structural-functional
      organization of the ACSM due to the action of relaxin-shown here for the first
      time-can be presented as the following signaling sequence: relaxin receptor
      ==>G(i) protein (betagamma-dimer) ==>phosphatidylinositol 3-kinase ==>protein
      kinase Czeta ==>G(s) protein ==>adenylyl cyclase. According to our hypothesis,
      the regulatory action of the insulin superfamily peptides on cell processes
      (proliferation, apoptosis, and metabolism) is mediated via ACSM.

PMID- 16580234
TI  - Individual differences in anxiety trait are related to spatial learning abilities
      and hippocampal expression of mineralocorticoid receptors.
AB  - Although high levels of anxiety might be expected to negatively influence
      learning and memory, it remains to be shown whether individual differences in
      anxiety may influence spatial learning and memory in outbred rat populations. We
      have studied this possibility in male Wistar rats whose levels of anxiety were
      first characterized as either high (HA) or low (LA) according to their behavior
      in the elevated plus maze or in the open field test. Subsequently, their
      performance in the Morris water maze was studied, a task dependent on hippocampal
      activity. Interestingly, LA rats showed a faster acquisition and better memory in
      the water maze when compared to HA rats. Indeed, this difference in performance
      could mainly be attributed to the increase in thigmotactic behavior (swimming in
      circles close to the maze walls) displayed by HA rats during spatial navigation.
      Glucocorticoids are known to affect the state of anxiety and the hippocampus is
      the main target of glucocorticoids in the brain. Hence, we investigated whether
      the hippocampal expression of the two classical corticosteroid receptors,
      mineralocorticoid (MR) and glucocorticoid (GR) differed in the two groups of
      rats. We found that LA rats displayed higher hippocampal expression of MR but not
      GR than HA rats. Indeed, the expression levels for these receptors were
      positively correlated with the amount of time spent by the animals in the open
      arms of the elevated plus maze. Moreover, we present evidence that the levels of
      anxiety quantified in the first stages of our study constitute a trait rather
      than a state. Taken together, this study has generated evidence of a close
      interaction between the anxiety trait, hippocampal MR expression and the learning
      abilities of individuals in stressful spatial orientation tasks.

PMID- 16580235
TI  - Haemoglobin A1c (HbA1C) in non-diabetic and diabetic vascular patients. Is HbA1C
      an independent risk factor and predictor of adverse outcome?
AB  - BACKGROUND: Plasma Haemoglobin A1c (HbA1c) reflects ambient mean glycaemia over a
      2-3 months period. Reports indicate that patients, with and without diabetes,
      with an elevated HbA1c have an increased risk of adverse outcome following
      surgical intervention. Our aim was to determine whether elevated plasma HbA1c
      level was associated with increased postoperative morbidity and mortality in
      patients undergoing vascular surgical procedures. METHODS: Plasma HbA1c was
      measured prospectively in 165 consecutive patients undergoing emergency and
      elective vascular surgical procedures over a 6-month period. Patients were
      categorized into four groups depending on whether their plasma HbA1c was < or
      =6%, 6.1-7%, 7.1-8% or >8% and clinical data was entered into a prospectively
      maintained database. Patients were also classified by diabetic status with
      suboptimal HbA1c in a patient without diabetes being >6 to < or =7% and
      suboptimal HbA1c in a patient with diabetes being >7%. Patients with plasma HbA1c
      >7% were reclassified as having undiagnosed diabetes mellitus. Composite primary
      endpoints were all cause 30-day morbidity and mortality and all cause 6-month
      mortality. Composite secondary endpoints were procedure specific complications,
      adverse cardiac events, stroke, infection and mean length of hospital stay.
      RESULTS: Of the 165 patients studied, 43 (26.1%) had diabetes and the remaining
      122 (73.9%) did not. The mean age was 72 years and 59% were male. Suboptimal
      HbA1c levels were found in 58% patients without diabetes and in 51% patients with
      diabetes. In patients without diabetes those with suboptimal HbA1c levels (6-7%)
      had a significantly higher incidence of overall 30-day morbidity compared to
      patients with HbA1c levels < or =6% (56.5 vs 15.7%, p<0.001). Similarly, for
      patients with diabetes those with suboptimal HbA1c levels (HbA1c >7%) had a
      significantly higher incidence of 30-day morbidity compared to those with HbA1c
      levels < or =7% (59.1% vs 19%, p=0.018). Multivariate analysis revealed that a
      plasma HbA1c level of >6 to < or =7% was a significant independent predictor of
      overall 30-day morbidity in patients without diabetes undergoing vascular
      surgical procedures. No difference in mortality, composite secondary endpoints,
      procedure specific complications, stroke or mean length of hospital stay was
      observed between any of the groups in the study. CONCLUSION: Suboptimal HbA1c
      levels may hold prognostic significance in patients without diabetes undergoing
      vascular surgery.

PMID- 16580237
TI  - Role of calcium signals in early development.
AB  - The mammalian egg appears to transduce the duration, amplitude, and temporal
      presentation of the increase in the intracellular calcium concentration
      ([Ca(2+)](i)) upon fertilization. These Ca(2+) parameters have important short
      term effects on the initiation and completion of early events of egg activation,
      as well as much later consequences for the extent of peri-implantation
      development. Recent studies have begun to shed light on how the egg
      quantitatively interprets the Ca(2+) signal (e.g., by summation of individual
      Ca(2+) rises) and the mechanisms by which down-stream Ca(2+) effectors, such as
      Ca(2+)/Calmodulin (CaM)-dependent protein kinase II (CaMKII), utilize this ionic
      signal to promote biological events that initiate development.

PMID- 16580236
TI  - A prospective analysis of fenestrated endovascular grafting: intermediate-term
      outcomes.
AB  - PURPOSE: To assess the intermediate-term outcomes following fenestrated grafting
      for juxtarenal aneurysms. MATERIALS AND METHODS: A prospective trial was
      conducted on patients with short proximal necks, who were considered to be high
      risk for open repair and unacceptable for conventional endovascular repair.
      Devices were designed from reconstructed CT data. Follow-up studies included CT,
      duplex ultrasound, and KUB and occurred at hospital discharge, 1, 6, and 12
      months and annually thereafter. RESULTS: One hundred and nineteen patients were
      treated (2001-2005). Mean age and aneurysm size were 75 years and 65 mm,
      respectively, and 82% were male. A total of 302 visceral vessels were inferior to
      the fabric seal (a mean of 2.5 vessels per patient), with the most common design
      incorporating two renal arteries and the SMA (58%). All prostheses were implanted
      successfully without any acute visceral artery loss. The mean follow-up was 19
      months (0-42 months). One patient died within 30 days of device implantation.
      Kaplan-Meier estimates of survival at 1, 12, 24, and 36 months are 0.99, 0.92,
      0.83 and 0.79. There were no ruptures or conversions. Pre-discharge imaging noted
      11 type I and type III endoleaks. The 30-day endoleak rate was 10% (all type II).
      Aneurysm sac size decreased (>5 mm) in 51, 79 and 77% at 6, 12 and 24 months,
      respectively. One patient had sac enlargement within the first year, associated
      with a persistent type II endoleak. In-stent stenoses occurred in 12 renal
      arteries and one SMA. Six renal arteries and the SMA stenosis were treated and
      two renal stenoses are awaiting treatment. Ten of 231 stented renal arteries
      occluded (three prior to discharge), one of which was recanalized. One component
      separation was treated with an extension at 2 years. CONCLUSIONS: The placement
      of endovascular prostheses with graft material incorporating the visceral
      arteries is safe and appears to be effective at preventing rupture. Continued
      follow-up to assess the long-term benefit, aneurysm sac behavior and effect of
      stenting upon the visceral ostia remains critical.

PMID- 16580238
TI  - Single-sided sensor for high-resolution NMR spectroscopy.
AB  - The unavoidable spatial inhomogeneity of the static magnetic field generated by
      open sensors has precluded their use for high-resolution NMR spectroscopy. In
      fact, this application was deemed impossible because these field variations are
      usually orders of magnitude larger than those created by the microscopic
      structure of the molecules to be detected. Recently, chemical shift resolved NMR
      spectra were observed for the first time outside a portable single-sided magnet
      by implementing a method that exploits inhomogeneities in the rf field designed
      to reproduce variations of the static magnetic field. In this communication, we
      describe in detail the magnet system built from permanent magnets as well as the
      rf coil geometry used to compensate the static field variations.

PMID- 16580240
TI  - The relationship between gut contents and supercooling capacity in hatchling
      painted turtles (Chrysemys picta).
AB  - Painted turtles (Chrysemys picta) typically spend their first winter of life in a
      shallow, subterranean hibernaculum (the natal nest) where they seemingly
      withstand exposure to ice and cold by resisting freezing and becoming
      supercooled. However, turtles ingest soil and fragments of eggshell as they are
      hatching from their eggs, and the ingestate usually contains efficient nucleating
      agents that cause water to freeze at high subzero temperatures. Consequently,
      neonatal painted turtles have only a modest ability to undergo supercooling in
      the period immediately after hatching. We studied the limit for supercooling
      (SCP) in hatchlings that were acclimating to different thermal regimes and then
      related SCPs of the turtles to the amount of particulate matter in their
      gastrointestinal (GI) tract. Turtles that were transferred directly from 26
      degrees C (the incubation temperature) to 2 degrees C did not purge soil from
      their gut, and SCPs for these animals remained near -4 degrees C for the 60 days
      of the study. Animals that were held at 26 degrees C for the duration of the
      experiment usually cleared soil from their GI tract within 24 days, but SCPs for
      these turtles were only slightly lower after 60 days than they were at the outset
      of the experiment. Hatchlings that were acclimating slowly to 2 degrees C cleared
      soil from their gut within 24 days and realized a modest reduction in their SCP.
      However, the limit of supercooling in the slowly acclimating animals continued to
      decline even after all particulate material had been removed from their GI tract,
      thereby indicating that factors intrinsic to the nucleating agents themselves
      also may have been involved in the acclimation of hatchlings to low temperature.
      The lowest SCPs for turtles that were acclimating slowly to 2 degrees C were
      similar to SCPs recorded in an earlier study of animals taken from natural nests
      in late autumn, so the current findings affirm the importance of seasonally
      declining temperatures in preparing animals in the field to withstand conditions
      that they will encounter during winter.

PMID- 16580239
TI  - Scorpion venom increases mRNA expression of lung cytokines.
AB  - Previous studies have demonstrated that scorpion toxins increase the serum levels
      of IL-1, IL-6, INF-gamma, and GM-CSF in patients with severe shock and pulmonary
      edema. Moreover, it has been shown that experimental models of scorpion
      envenomation presented an increase in serum levels of IL-1, IL-6, IFN-gamma and
      nitric oxide. Thus, it is possible that the cytokine release may contribute to
      the onset and maintenance of the pulmonary edema induced by scorpion venom. This
      study was designed to investigate whether inflammatory and non-inflammatory
      cytokines, contribute to the pulmonary injury induced by infusion of Tityus
      serrulatus scorpion toxin in rats. We show that scorpion venom not only increases
      the expression of mRNA pulmonary inflammatory cytokines but also non-inflammatory
      cytokines as well. Moreover, the expression of IL-1alpha, IL-1beta and IL-6 mRNA
      was shown to be higher among the remaining detectable cytokines. The findings of
      this study provide additional insight towards the understanding of the
      pathophysiology of the pulmonary edema induced by scorpion venom. The increased
      level of pulmonary cytokines observed during the pulmonary edema may be
      responsible for the exacerbation and maintenance of the inflammatory response to
      scorpion venom in the lungs.

PMID- 16580241
TI  - Evaluation of thermal acclimation capacity in corals with different thermal
      histories based on catalase concentrations and antioxidant potentials.
AB  - Colonies of Pocillopora damicornis from Kaneohe Bay and colonies of Pocillopora
      meandrina from a thermal outfall site and a control site at Kahe were exposed to
      three different temperatures (29, 32 and 33 degrees C) in outdoor aquaria on
      running water tables for five days. Samples (n=3) were taken from each treatment
      at 0800, 1200 and 1600 h. ELISAs using catalase antibodies and ferric
      reducing/antioxidant potential (FRAP) assays were run on the samples to determine
      how antioxidant levels changed throughout the experiment. Light levels during the
      experiment were highest in the morning ( approximately 1000-1500 micromol quanta
      m(-2) s(-1)) and decreased to 25-60 micromol quanta m(-2) s(-1) by 1100 h and
      remained low until sunset. Antioxidant concentrations were highest in the morning
      for P. damicornis from Kaneohe and P. meandrina outfall samples. There was no
      significant change through the day for P. meandrina samples from the control
      site. The difference in response between the outfall samples and the control
      samples suggests that P. meandrina has acclimated to elevated temperatures found
      at the outfall site.

PMID- 16580242
TI  - Visual function and dysfunction in early and late age-related maculopathy.
AB  - Late age-related maculopathy (ARM) is responsible for the majority of blind
      registrations in the Western world among persons over 50 years of age. It has
      devastating effects on quality of life and independence and is becoming a major
      public health concern. Current treatment options are limited and most aim to slow
      progression rather than restore vision; therefore, early detection to identify
      those patients most suitable for these interventions is essential. In this work,
      we review the literature encompassing the investigation of visual function in ARM
      in order to highlight those visual function parameters which are affected very
      early in the disease process. We pay particular attention to measures of acuity,
      contrast sensitivity (CS), cone function, electrophysiology, visual adaptation,
      central visual field sensitivity and metamorphopsia. We also consider the impact
      of bilateral late ARM on visual function as well as the relationship between
      measures of vision function and self-reported visual functioning. Much interest
      has centred on the identification of functional changes which may predict
      progression to neovascular disease; therefore, we outline the longitudinal
      studies, which to date have reported dark-adaptation time, short-wavelength cone
      sensitivity, colour-match area effect, dark-adapted foveal sensitivity, foveal
      flicker sensitivity, slow recovery from glare and slower foveal electroretinogram
      implicit time as functional risk factors for the development of neovascular
      disease. Despite progress in this area, we emphasise the need for longitudinal
      studies designed in light of developments in disease classification and retinal
      imaging, which would ensure the correct classification of cases and controls, and
      provide increased understanding of the natural course and progression of the
      disease and further elucidate the structure-function relationships in this
      devastating disorder.

PMID- 16580243
TI  - The epidemiology of drug facilitated sexual assault.
AB  - The files of the Victorian Institute of Forensic Medicine were reviewed for all
      cases of alleged drug facilitated sexual assault for the 12 month period
      concluding in April 2003. Seventy-six cases were identified from a total of 434
      (17.5%) cases of adult sexual assault. The median delay from alleged incident to
      time of examination was 20 h. Alcohol consumption in the hours prior to the
      assault was reported by 77%. Alcohol was still present in 37% when subsequently
      examined, with an average blood alcohol concentration of 0.11% at the time of
      examination. Forty-nine percent reported using prescription medications and 26%
      reported the use of recreational drugs. Drugs not reportedly consumed by the
      subject were detected in 15 cases (20%) of the study group or 3% of all adult
      sexual assault cases. The drugs detected included cannabis (four cases),
      antidepressants (4), amphetamines (3), benzodiazepines (4) and opiates (3). The
      study indicates that covert administration of drugs in the setting of adult
      sexual assault appears uncommon. The true incidence however may be higher (due to
      non or delayed reporting) or lower (due to inaccurate self reporting of drug
      consumption) however the frequent findings of high concentrations of alcohol has
      implications for the health and safety of these individuals.

PMID- 16580244
TI  - The use of an alternative light source to detect semen in clinical forensic
      medical practice.
AB  - One of the primary aims of forensic examination in sexual offences is to detect
      and recover biological material that will link the offender with the complainant.
      One potentially valuable method by which trace biological evidence may be
      identified in other forensic settings is via the use of an Alternate Light Source
      (ALS). The aim of this study was to determine whether or not there was any
      potential benefit in using an ALS as an adjunct in sexual assault examinations to
      aid the detection of forensically relevant areas on the body which are not
      identifiable on visual inspection for sampling. We present two case reports,
      which illustrate the potential value of using an ALS in clinical forensic medical
      practice as an adjunct in sexual assault examinations to detect potentially
      forensically useful areas of skin to sample for semen. Prior to introducing the
      ALS into our clinical forensic medical practice, we undertook a number of simple
      laboratory studies to determine a protocol for its use. Semen is known to
      fluoresce using an ALS at a wavelength of 450 nm. Although we did not conduct a
      rigorous scientific evaluation of the technique, we evaluated the use of an ALS
      to detect semen on a range of inanimate surfaces as well as human skin. On all
      surfaces, visibility of fluorescence was increased by reduced distance of light
      source from the surface and increased concentration of semen on the surface, but
      was not noticeably affected by the angle at which the light source was held in
      relation to the surface.

PMID- 16580245
TI  - Interpreting evidence in court - the dangers and pitfalls.

PMID- 16580246
TI  - Mental health and the city: intra-urban mobility among individuals with
      schizophrenia.
AB  - Intra-urban residential mobility of a cohort with schizophrenia was compared to a
      matched cohort with no mental illness using population-based administrative data.
      The percentage of individuals with one or more changes in postal code in the
      three-year mobility study period was examined, along with measures of the
      movement between different intra-urban areas. The schizophrenia cohort was more
      likely to move than the matched cohort; however, this depends on their age,
      income level, and area of residence at baseline. Age, gender, marital status,
      income quintile, and use of physicians and hospitalizations were associated with
      mobility. Individuals in the schizophrenia cohort were significantly more likely
      to move from the suburb to the inner city, and significantly less likely to move
      from the inner city to the suburb than those with no mental illness. Implications
      of the findings and directions for future research are discussed, with particular
      attention paid to the utility of administrative data for further mental health
      research.

PMID- 16580247
TI  - A decade of contact lens prescribing trends in the United Kingdom (1996-2005).
AB  - PURPOSE: To document contact lens prescribing trends in the United Kingdom over
      the past decade (between 1996 and 2005). METHODS: An annual survey of contact
      lens prescribing trends was conducted each year by asking a random selection of
      optometrists and dispensing opticians to provide information relating to 10
      consecutive contact lens fits between January and March. RESULTS: Over the 10
      year survey period, 1251 practitioners returned survey forms representing a total
      of 12,050 contact lens fits. The mean (+/-standard deviation) age of lens wearers
      was 33+/-13 years of which 64% were female. Over the survey period, rigid lens
      new fits decreased from 22% to 4%. Low water content lenses reduced from 20% to
      2% of new soft lens fits. Soft toric lenses gradually increased to the point
      where they accounted for the expected proportion of patients with
      astigmatism>or=1.00DC (i.e. >20% of soft lens fits). Monthly and daily disposable
      lenses accounted for >90% of all soft lens fits between 2003 and 2005. The
      proportion of new soft fits and refits prescribed as extended wear has gradually
      increased, stabilizing at about 5% of new fits and 12% of refits. Multi-purpose
      lens care solutions increased from 60% of all care systems in 1997 to 91% in
      2005. Rigid lenses and monthly replacement soft lenses are predominantly worn on
      a full time basis, whereas daily disposable soft lenses are mainly worn part
      time. CONCLUSIONS: This survey indicates that technological advancements such as
      the development of new lens materials, manufacturing methods and lens designs
      have had a significant impact on the contact lens market over a relatively short
      period of time.

PMID- 16580248
TI  - Genetically unique microsporidian Encephalitozoon cuniculi strain type III
      isolated from squirrel monkeys.
AB  - Microsporidian spores were isolated from two squirrel monkeys (Saimiri sciureus)
      that had been bred at an animal-breeding colony in Japan. The spores were
      identified as Encephalitozoon cuniculi on the basis of nucleotide sequence
      analysis of the small-subunit (SSU) rRNA gene. The internal transcribed spacer
      (ITS) gene sequence revealed that these isolates were classified into genotype
      III because it contained tetrarepeats of 5'-GTTT-3'. However, the sequences of
      the polar tube protein (PTP) gene of the monkey isolates were not identical to a
      reported sequence of genotype III but were quite similar to a reported sequence
      of genotype II. On the other hand, sequence analysis of the spore wall protein 1
      (SWP-1) gene revealed that the monkey isolates did not belong to any of genotypes
      I, II and III. These results suggest that the present E. cuniculi isolates of
      squirrel monkey origin are a new subtype of E. cuniculi ITS genotype III that can
      cause a disseminated infection.

PMID- 16580249
TI  - Rectification of excitation with bathochromic shift induced by intense absorption
      of organic ligands during emission measurement of Eu(III) complex.
AB  - Bathochromic shift in excitation spectrum was observed during emission
      measurement of Eu(DBM)(3)Phen containing dilute solution in methyl methacrylate
      (MMA). Detailed analysis shows that the reason of bathochromic shift is not the
      formation of molecule aggregation. It is caused by the intense absorption of
      ligands in the complex. Based on this model, a new method has been established to
      rectify excitation spectra before emission measurement of systems with different
      concentration. There exists a critical value of the absorption strength, which is
      0.87 from calculation. Higher absorption than this value will cause the
      bathochromic shift of excitation peak. The wavelength whose absorbance is 0.87
      will be the position of the strongest excitation peak. With 200 ppm and 500 ppm
      Eu(DBM)(3)Phen as the standard sample, relations between relative concentration
      and wavelength of excitation peak in Eu(DBM)(3)Phen system were deduced and
      plotted. Theoretical curves are in good agreement with experiment data except
      extra-dilute concentration, for partial decomplexation of the beta-diketonate and
      phenanthroline ligands.

PMID- 16580251
TI  - Comparison of global positioning and computer-based tracking systems for
      measuring player movement distance during Australian football.
AB  - Sports scientists require a thorough understanding of the energy demands of
      sports and physical activities so that optimal training strategies and game
      simulations can be constructed. A range of techniques has been used to both
      directly assess and estimate the physiological and biochemical changes during
      competition. A fundamental approach to understanding the contribution of the
      energy systems in physical activity has involved the use of time-motion studies.
      A number of tools have been used from simple pen and paper methods, the use of
      video recordings, to sophisticated electronic tracking devices. Depending on the
      sport, there may be difficulties in using electronic tracking devices because of
      concerns of player safety. This paper assesses two methods currently used to
      measure player movement patterns during competition: (1) global positioning
      technology (GPS) and (2) a computer-based tracking (CBT) system that relies on a
      calibrated miniaturised playing field and mechanical movements of the tracker. A
      range of ways was used to determine the validity and reliability of these methods
      for tracking Australian footballers for distance covered during games.
      Comparisons were also made between these methods. The results indicate distances
      measured using CBT overestimated the actual values (measured with a calibrated
      trundle wheel) by an average of about 5.8%. The GPS system overestimated the
      actual values by about 4.8%. Distances measured using CBT in experienced hands
      were as accurate as the GPS technology. Both systems showed relatively small
      errors in true distances.

PMID- 16580250
TI  - Angiotensin stimulates phosphatidylcholine synthesis via a pathway involving
      diacylglycerol, protein kinase C, ERK1/2, and CTP:phosphocholine
      cytidylyltransferase.
AB  - We are probing the regulation of phosphatidylcholine (PC) synthesis by
      angiotensin II. In the accompanying paper, we showed that manipulation of the
      lipid second messengers, arachidonic acid or hydroxyeicosatetraenoic acid,
      produced downstream of the angiotensin AT1a receptor did not affect the PC
      synthesis rates in a manner consistent with direct activation of the rate
      limiting enzyme in the pathway, CTP:phosphocholine cytidylyltransferase (CCT).
      However, suppression of diacylglycerol (DAG) production with an inhibitor of
      phospholipase C-beta reduced angiotensin-dependent PC synthesis as well as ERK1/2
      phosphorylation. Here, we show that the stimulation of PC synthesis and
      activation of CCT by angiotensin requires a signaling pathway that involves
      protein kinase C and ERK1/2. The inhibitors bis-indolylmaleimide I and PD98059
      blocked ERK1/2 phosphorylation and completely eliminated angiotensin stimulation
      of the CCT-catalyzed reaction and PC synthesis. Exogenous addition of DAG using a
      lipid vesicle delivery system exactly mimicked the kinetics of angiotensin
      promoted PC synthesis, suggesting that this mode of DAG delivery can effectively
      substitute for the DAG generated downstream of the activated AT1a receptor.
      Moreover, exogenous DAG activated ERK1/2, and the activation of PC synthesis by
      DAG was blocked by inhibition of protein kinase C and MEK. These data suggest
      that angiotensin-dependent DAG and the exogenously supplied DAG stimulate PC
      synthesis, not solely by direct action on CCT, but via a signaling pathway
      involving protein kinase C and ERK1/2. Angiotensin did not alter the net
      phosphorylation state of CCT as probed by immunoprecipitation of 32P-labeled CCT.
      Angiotensin stimulation of ERK1/2 likely mediates effects on CCT via a process
      other than CCT dephosphorylation.

PMID- 16580252
TI  - Pedometer steps in primary school-aged children: a comparison of school-based and
      out-of-school activity.
AB  - While studies of the physical activity habits of New Zealand children have been
      carried out, the findings have been restricted by the use of proxy and self
      report measures and limited to total overall daily activity. Objective
      measurement of children's in-school and out-of school physical activity using
      pedometry is likely to provide more accurate data on habitual daily activity. To
      date, no such data are available for New Zealand children. In the present study,
      children from school years 1-6 (girls, n=46; boys, n=45) at a New Zealand primary
      school wore a Yamax Digiwalker SW-200 pedometer to record school-based and out-of
      school steps over a 3-day period. Mean daily steps for the overall sample were 14
      333 (S.D.=4110). Boys (X=15 606; S.D.=4601) were significantly more active than
      girls (X=13 031; S.D.=3079) (p=.00). Mean steps were also significantly higher in
      older age groups for both boys (p=.03) and in particular, girls (p=.00). Of note,
      for the overall sample, steps taken out of school made up 52.4% of total daily
      steps. Girls (53.6%) and boys (51.3%) took a similar proportion of their overall
      daily steps outside of the school environment. While a significant difference was
      found between the most and least active tertiles in steps taken during both
      during school hours (p=.00) and outside of school hours (p=.00), the most active
      third of the sample completed significantly more of their daily steps outside of
      school (55.1%) than did their least active (46.7%) counterparts (p=.00). These
      results suggest that physical activity outside of the school environment is a key
      contributor to a child's overall level of physical activity, reinforcing the need
      for interventions targeting the family and community as well as the school
      environment.

PMID- 16580253
TI  - Acute neuromuscular responses to resistance training performed at different
      loads.
AB  - The aim of this study was to compare the acute neuromuscular responses during
      resistance exercise performed with different loading protocols. Thirteen (N=13)
      college-aged male subjects experienced in weight training completed two different
      weight training protocols involving a single elbow flexion exercise. During both
      protocols subjects performed three sets of the exercise with a 3-min rest between
      each set. One protocol required the subjects to perform each set to failure using
      100% 10 repetition maximum (RM) load whereas the second protocol required the
      subjects to perform 10 repetitions for the first two sets using 90% 10RM load and
      only go to failure on the third set. Maximal voluntary isometric contraction
      (MVIC), integrated EMG recording (iEMG) of the biceps brachii, and blood lactate
      were measured before and upon completion of the two training protocols. Subjects
      were able to perform a significantly greater volume of work (total
      repetitionsxload) in the 90% 10RM protocol compared to the 100% 10RM protocol.
      Both protocols elicited similar cumulative levels of fatigue as reflected by a
      decrease in MVIC and iEMG(max) and an increase in blood lactate (p< or =0.05). As
      a result of the drop in repetitions performed in successive sets, it was
      concluded that training with 100% 10RM while exercising to failure in each set
      may not optimise the training volume, which may have implications for chronic
      muscle adaptation.

PMID- 16580254
TI  - Sharing the research agenda: confronting what we believe to be the nursing
      contribution to research in cancer care.

PMID- 16580256
TI  - Peroxisome proliferator-activated receptors and acute lung injury.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily of ligand-activated transcription factors that are
      related to retinoid, steroid and thyroid hormone receptors. The PPAR subfamily
      comprises three members: PPAR-alpha, PPAR-beta and PPAR-gamma. PPARs have
      recently been implicated as regulators of cellular proliferation and inflammatory
      responses. Furthermore, it has been demonstrated that PPAR-gamma and PPAR-alpha
      reduce lung injury associated with inflammation and shock.

PMID- 16580255
TI  - In defense of the lung: surfactant protein A and surfactant protein D.
AB  - The lung is repeatedly exposed to inhaled particles and pathogens that are
      cleared by the actions of a multi-component innate host defense system. The
      pulmonary collectins--surfactant proteins A (SP-A) and D (SP-D)--play important
      roles in innate host defense by binding and clearing invading microbes from the
      lung. SP-A and SP-D also influence surfactant homeostasis, contributing to the
      physical structures of lipids in the alveoli and to the regulation of surfactant
      function and metabolism. In addition to binding and opsonizing infectious
      pathogens, SP-A and SP-D bind to the surfaces of host defense cells, promoting or
      inhibiting immune cell activity through multiple cellular pathways. As a
      consequence of their physiologic functions, SP-A- and SP-D-dependent pathways are
      targets for clinical therapies designed to limit the proliferation of
      microoorgansims and to ameliorate inflammation following pulmonary infection.

PMID- 16580257
TI  - Therapeutic applications of carbon monoxide in lung disease.
AB  - Carbon monoxide (CO) offers potential therapeutic avenues in the treatment of
      lung disorders. CO arises endogenously from heme degradation, catalyzed by the
      heme oxygenase enzymes. In cell culture, CO exerts potent anti-inflammatory, anti
      apoptotic and anti-proliferative effects by modulating intracellular signaling
      pathways. In vivo, CO confers tissue protection in animal models of lung disease,
      including those with oxidative and inflammatory lung injury and
      ischemia/reperfusion injury. Furthermore, low-dose CO ameliorates vascular injury
      and reduces the rejection rate of lung and vascular grafts. Recent advances
      include the observation that CO protects the lung in models of bleomycin-induced
      lung fibrosis and ventilator-induced lung injury. Despite the success of CO
      therapy in animal models, the utility of CO as therapy in humans remains
      uncertain.

PMID- 16580258
TI  - TLR signaling and trapped vascular dendritic cells in the development of
      atherosclerosis.
AB  - The Framingham Heart Study established a link between serum lipoproteins and
      atherosclerosis but a crucially important feature of the disease has been
      neglected: it is primarily an immunological disorder. Here, we reframe
      atherosclerosis in terms of recent progress in understanding the immunological
      mechanisms underlying the disorder, and advance a new conceptual model for the
      future. We place vascular dendritic cells squarely at the forefront, and propose
      that a sentinel network of vascular dendritic cells (DCs) sample and process
      exogenous and endogenous antigens that can trigger an inflammatory nidus within
      the arterial wall. Our model postulates that two components are essential to the
      development of atheromata: vascular DCs and intact myeloid differentiation
      (MyD)88-dependent signaling by Toll-like receptors.

PMID- 16580259
TI  - Avoiding autoimmune disease--T cells know their limits.
AB  - The molecular mimicry theory has become a dominant paradigm to explain the
      triggering of autoaggressive T lymphocytes. The basis of the theory is that an
      immune response is triggered by non-self during infection and subsequent cross
      reactive T-cell recognition of a similar self antigen provokes an inflammatory
      lesion in the target organ. It is clear that we all harbour autoreactive T cells
      and that T-cell receptor (TCR) cross-reactivity is extensive. Here, I argue that
      the immune system has evolved mechanisms to limit the risk of an autoaggressive
      response. Importantly, the strength of TCR stimulation provided by self and non
      self antigens will usually differ. Evidence points to a model in which the three
      pillars of immune tolerance (deletion, anergy-adaptation and regulation) act to
      limit autoimmune disease from molecular mimicry.

PMID- 16580260
TI  - A unified theory of central tolerance in the thymus.
AB  - Non-deletional tolerance resulting in the generation of regulatory T cells within
      the thymus is a key mechanism for the establishment of immunological self
      tolerance. How the high-affinity self-reactive regulatory T cells escape negative
      selection and what type of antigen-presenting cells positively select them within
      the thymus are unsolved questions. Previous studies suggest that thymic
      epithelial cells are crucial for the positive selection of regulatory T cells in
      thymus. A recent study from my group shows that a subset of dendritic cells (that
      have been "educated" by the thymic stromal lymphopoietin molecule produced by a
      thymic cell type known as Hassall's corpuscles) positively select regulatory T
      cells within the medulla of human thymus. Here, I discuss the implications and
      historical context of this new result and suggest that a subset of mature
      dendritic cells within the thymic medulla protects the medium- to high-affinity
      self-reactive T cells from negative deletion and induces their differentiation
      into regulatory T cells in the thymus.

PMID- 16580261
TI  - T-cell homing specificity and plasticity: new concepts and future challenges.
AB  - Naive and effector/memory T cells have distinct repertoires of trafficking
      ligands and receptors that restrict their ability to interact with specialized
      microvessels in different anatomical compartments and, consequently, have
      distinct patterns of migration. Antigen-experienced lymphocytes can be further
      subdivided into different subsets based on their expression of characteristic
      sets of trafficking receptors that favor their accumulation in certain target
      organs, including the skin and gut. Here, we summarize recent advances that have
      broadened our understanding of the cellular and molecular events that induce the
      generation of tissue-specific effector/memory T cells and discuss how these
      mechanisms could be harnessed for the therapeutic manipulation of T-cell
      dependent pathologies.

PMID- 16580262
TI  - Conceptual models used by nurses working in coronary care units--a discussion
      paper.
AB  - In the UK, Europe and the USA conceptual models of nursing are features of many
      undergraduate nursing curricula [Alligood MR. The nature of knowledge needed for
      nursing practice. In Alligood MR, Marriner-Tomey A, editors. Nursing theory
      utilisation and application. London: Mosby, 2002, Tierney AJ. Nursing models
      extant or extinct? J Adv Nurs 1998;8(1):77-85] and commonly used in practice.
      However, UK nurses in practice continue to be dissatisfied with conceptual model
      use [Griffiths P. An investigation into the description of patients' problems by
      nurses using two different needs-based nursing models. J Adv Nurs 1998;28(5):969
      977, Mason C. Guide to practice or 'load of rubbish'? The influence of care plans
      on nursing practice in five clinical areas in Northern Ireland. J Adv Nurs
      1999;29(2):380-387, Murphy K, Cooney A, Casey D, Connor M, O'Connor J., Dineen B.
      The Roper, Logan and Tierney Model: perceptions and operationalization of the
      model in psychiatric nursing within one health board in Ireland. J Adv Nurs
      2000;31(6):1333-1341]. An association with increased paperwork and documentation
      together with a belief that these abstract concepts do not quite fit with the
      practice setting has resulted in a generalised apathy towards their use in some
      areas [Timmins F. Critical care nursing in the 21st Century. Intensive Crit Care
      Nurs 2002;18:118-127]. In an era of concerns about both cost and quality,
      together with an increased impetus towards multi-professional working patterns
      and role expansion, alternative models of care, such as critical pathways and
      care pathways are gaining increased favour in the clinical setting [Johnson S,
      editor. Pathways of care. Oxford; Blackwell Science 1997]. The aim of this paper
      is to consider whether or not the traditional conceptual models of nursing are
      apt for today's practicing coronary care nurse. Specific questions to be
      addressed are: what is the research evidence that informs conceptual model use in
      coronary care and what are the conceptual models that commonly inform
      contemporary practice in coronary care nursing? Suggested ways forward for
      conceptual model use within nursing are also proposed.

PMID- 16580263
TI  - Anti-endothelial cell antibodies from patients with limited cutaneous systemic
      sclerosis bind to centromeric protein B (CENP-B).
AB  - By using a quantitative immunoblotting technique on protein extracts of human
      macrovascular and microvascular endothelial cells, we have analyzed the self
      reactive repertoires of IgG from 20 patients with limited cutaneous SSc, 40
      patients with diffuse SSc and 60 age- and sex-matched healthy controls. Serum IgG
      from 15/20 patients with limited cutaneous SSc and anti-centromere antibodies
      bound to at least one of the two 75- and 85-kDa protein bands in the different
      endothelial cell extracts, whereas IgG from healthy controls or patients with
      diffuse SSc did not. N-terminal sequencing of the 75- and 85-kDa bands identified
      CENP-B as the sole antigen in both bands. Moreover, IgG from all of the SSc
      patients who recognized the 75- and/or 85-kDa bands bound to a full-length
      recombinant CENP-B protein as assessed by ELISA, whereas IgG from other SSc
      patients did not. The main target of anti-endothelial cell antibodies in patients
      with limited cutaneous SSc is the nuclear and ubiquitous protein CENP-B.

PMID- 16580264
TI  - Triple-targeted oncolytic adenoviruses featuring the cox2 promoter, E1A
      transcomplementation, and serotype chimerism for enhanced selectivity for ovarian
      cancer cells.
AB  - Conditionally replicating adenoviruses (CRAd's) feature selective replication in
      and killing of tumor cells. Initial clinical studies with relatively attenuated
      early generation agents have resulted in promising safety and efficacy data.
      Nevertheless, increased specificity may be advantageous for an emerging
      generation of infectivity-enhanced CRAd's. Further, increased specificity could
      translate into a larger tolerated dose. An approach for increasing specificity is
      dual control of E1A expression. We constructed six CRAd's featuring two variants
      of the cyclo-oxygenase 2 (cox2) promoter, combined with three versions of E1A.
      Transcriptional targeting was supplemented with transductional targeting
      utilizing the serotype 3 knob. In vivo and in vitro results suggest that cox2 can
      be utilized for enhancing the specificity of E1A deletion mutants and that
      combination with the Delta24 mutation increases specificity without reducing
      potency. Combination with Delta2-Delta24 was specific but somewhat attenuated.
      The promoter variants behaved similarly, although the longer 1,554-bp version
      displayed a trend for improved specificity. Transcriptional modifications were
      compatible with transductional targeting and resulted in up to 100,000-fold
      increase in the therapeutic window for Ad5/3cox2Ld24 vs wild-type adenovirus.
      Thus, the proposed triple-targeting strategy may be useful for increasing the
      safety and efficacy of adenoviral gene therapy for ovarian cancer.

PMID- 16580265
TI  - Effects of antagonists for endothelin ET(A) and ET(B) receptors on coronary
      endothelial and myocardial function after ischemia-reperfusion in anesthetized
      goats.
AB  - To compare the effects of antagonists for endothelin ET(A) and ET(B) receptors on
      the action of ischemia-reperfusion on endothelial and myocardial function, 30 min
      of partial or total occlusion followed by 60 min of reperfusion of the left
      circumflex coronary artery was induced in anesthetized goats treated with
      intracoronary administration of saline (vehicle), BQ-123 (endothelin ET(A)
      receptors antagonist) or BQ-788 (endothelin ET(B) receptors antagonist). During
      reperfusion after partial occlusion, coronary vascular conductance and left
      ventricle dP/dt were decreased after saline or BQ-788, and they normalized after
      BQ-123. In these three groups of animals, the coronary effects of acetylcholine
      (3-100 ng) and sodium nitroprusside (1-10 microg) during reperfusion were as
      under control. During reperfusion after total occlusion, coronary vascular
      conductance and left ventricle dP/dt were decreased after saline, and they
      normalized after BQ-123 or BQ-788. In these three groups of animals, the coronary
      effects of acetylcholine but not those of sodium nitroprusside during reperfusion
      were decreased after saline, and they reversed after BQ-123 or BQ-788. Therefore,
      selective antagonists of endothelin ET(B) and ET(A) receptors may produce similar
      protection of coronary vasculature and myocardium against reperfusion after
      severe ischemia. Selective antagonists of endothelin ET(B) receptors, contrarily
      to those of endothelin ET(A) receptors, may be ineffective to protect coronary
      vasculature and myocardium against reperfusion after mild ischemia.

PMID- 16580266
TI  - Enhanced c-Fos expression in the rostral ventral respiratory complex and rostral
      parapyramidal region by inhibition of the Na+/H+ exchanger type 3.
AB  - Previous studies have shown that selective inhibition of Na+/H+ exchanger type 3
      (NHE3) induces intracellular acidification and activates CO2/H+-sensitive
      medullary neurons, mimicking the responses evoked by hypercapnic stimuli. In
      addition, NHE3 blockers administration decreases the duration of apnoea induced
      by laryngeal stimulation, presumably by means of central chemoreceptor
      activation. To test the hypothesis that the central chemoreceptor network may be
      affected by NHE3 inhibition, brainstem c-Fos immunoreactive cell counting was
      performed after systemic administration of the NHE3 blocker AVE1599 (Aventis
      Pharma Deutschland GmbH) (2 mg/kg). The rostro-caudal quantitative c-Fos analysis
      showed a significant increase in the number of c-Fos positive cells in the
      rostral part of the ventral respiratory complex (VRC) as well as in the rostral
      part of the parapyramidal (Ppy) region. The VRC activated region (-4.2 to -3.2mm
      interaural) included the pre-Botzinger complex, the rostral ventral respiratory
      group and the rostral ventrolateral medulla, all of them involved in
      cardiorespiratory control. The activated Ppy region corresponded with the rostral
      chemosensitive area, which elicits the strongest ventilatory response upon
      ventral medullary surface stimulation with H+/CO2. Most cells activated in Ppy
      after NHE3 inhibition were serotonergic. Hence, systemic application of NHE3
      blockers may induce central chemoreceptors activation and an increase in the
      respiratory network activity in a similar way to known physiological stimuli such
      as hypercapnia. On the other hand, selective NHE3 blockers could be excellent
      tools for treatment of pathological states where central chemoreceptor function
      is diminished or absent, such as central hypoventilation syndrome or sudden
      infant death syndrome.

PMID- 16580268
TI  - A validated gas chromatographic-electron impact ionization mass spectrometric
      method for methylenedioxymethamphetamine (MDMA), methamphetamine and metabolites
      in oral fluid.
AB  - An analytical method to simultaneously quantify amphetamine (AMP),
      methamphetamine (MAMP), methylenedioxymethamphetamine (MDMA),
      methylenedioxyamphetamine (MDA), methylenedioxyethylamphetamine (MDEA), 3-hydroxy
      4-methoxy-methamphetamine (HMMA) and 3-hydroxy-4-methoxy-amphetamine (HMA) in
      oral fluid is presented. Four hundred microlitres of oral fluid collected via
      expectoration was extracted by solid phase extraction. GC/MS-EI with selected ion
      monitoring (SIM) yielded linear curves 5-250 ng/mL for AMP, MAMP, MDMA and MDEA,
      5-500 ng/mL for MDA and 25-1,000 ng/mL for HMA and HMMA. Recoveries were greater
      than 85%, accuracy 87-104%, and precision less than 8.3% coefficient of
      variation. This assay will be used to investigate distribution of sympathomimetic
      amines into human oral fluid following controlled drug administration.

PMID- 16580267
TI  - Short-term receptor trafficking in the dorsal vagal complex: an overview.
AB  - Sensory information from the gastrointestinal (GI) tract is transmitted centrally
      via primary afferents that terminate within the nucleus of the tractus solitarius
      (NTS) and utilize glutamate as their major neurotransmitter. Neurons of the NTS
      integrate this sensory information and transmit it to parasympathetic
      preganglionic neurons of the dorsal motor nucleus of the vagus (DMV), as well as
      to other areas, using principally glutamate, GABA and norepinephrine as
      neurotransmitters. Although susceptible to modulation by a vast array of
      neurotransmitters, the glutamatergic NTS to DMV synapse seems to play a minor
      role in the tonic modulation of gastric vagal reflexes. GABAergic
      neurotransmission between the NTS and DMV, however, is of critical importance as
      its in vivo blockade induces dramatic effects on gastric tone, motility and
      secretion. In in vitro experiments, however, this synapse appears initially
      resistant to modulation by most exogenously applied neuromodulators. Using opioid
      peptides as a model, this review will discuss the remarkable plasticity of the
      NTS-DMV GABAergic synapse. Modulation of this synapse appears dependent upon the
      levels of cAMP within the brainstem circuit. In particular, this review will
      outline how vagal afferent inputs appear to dampen the cAMP-PKA system via tonic
      activation of metabotropic glutamate receptors. Removal of vagal sensory input,
      coincident activation of the cAMP-PKA system, or inhibition of group II
      metabotropic glutamate receptors, allows receptor trafficking to occur
      selectively at the level of the NTS-DMV GABAergic synapse. Thus, we propose that
      the state of activation of vagal sensory inputs determines the gastric motor
      response via selective engagement of GABAergic synapses. This mini-review is
      based upon a presentation given at the International Society for Autonomic
      Neuroscience meeting in Marseille, France in July 2005.

PMID- 16580269
TI  - Simple and rapid high-performance liquid chromatographic method for determination
      of celecoxib in plasma using UV detection: application in pharmacokinetic
      studies.
AB  - A rapid, sensitive and reproducible HPLC method was developed and validated for
      the analysis of celecoxib in human plasma. The analysis was carried out on a
      monolithic silica column using UV detection at 254 nm. The assay enables the
      measurement of celecoxib for therapeutic drug monitoring with a minimum
      quantification limit of 10 ng ml(-1). The method involves simple, one-step
      extraction procedure, and analytical recovery was 100.5 +/- 1.3%. The calibration
      curve was linear over the concentration range of 10-800 ng ml(-1). The
      coefficients of variation for inter-day and intra-day assay were found to be less
      than 8%. We also demonstrate the applicability of this method for pharmacokinetic
      studies in humans.

PMID- 16580271
TI  - Kinetic study of racemization of aspartyl residues in recombinant human alphaA
      crystallin.
AB  - Asp58 and Asp151 in human lens alphaA-crystallin invert and isomerize to d-beta
      aspartyl residues with age. Here, we report that the racemization rate constants
      (k) of Asp58 and Asp151 residues in human recombinant alphaA-crystallin at 37
      degrees C are 3.72 +/- 0.8 x 10(-4) and 10.7 +/- 0.7 x 10(-4)/day, respectively.
      The activation energy of racemization of Asp58 and Asp151 in the protein was 27.0
      +/- 0.5 kcal/mol and 21.0 +/- 0.5 kcal/mol, respectively. The time required for
      the D/L ratio of Asp58 and Asp151 to approximate to 1.0 (D/L ratio of Asp = 0.99)
      at 37 degrees C was estimated as 20.9 +/- 3.7 and 6.80 +/- 0.4 years,
      respectively. Thus, Asp151 is more susceptible to racemization than Asp58,
      consistent with data from short model peptides. However, the racemization rates
      of both Asp58 and Asp151 residues in the protein were twice as rapid as in model
      peptides. These results indicate that the racemization of Asp residues in alphaA
      crystallin may be influenced not only by the primary structure but also by the
      higher order structure around Asp residues in the protein.

PMID- 16580270
TI  - The role of tyrosine 177 in human 11beta-hydroxysteroid dehydrogenase type 1 in
      substrate and inhibitor binding: an unlikely hydrogen bond donor for the
      substrate.
AB  - The catalytic motif (YSASK) at the active site of 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) is conserved across different species. The
      crystal structures of the human, guinea pig and mouse enzymes have been resolved
      to help identify the non-conserved residues at the active site. A tyrosine
      residue (Y177) upstream of the catalytic motif in human 11beta-HSD1 represents
      the largest difference at the active sites between the human and the rodent
      enzyme where the corresponding residue is glutamine. Although Y177 was postulated
      as a potential hydrogen bond donor in substrate binding in crystal structure
      based modeling, no experimental evidence is available to support this notion.
      Here, we report that Y177 is not a hydrogen bond donor in substrate binding
      because removal of the hydroxyl group from its side chain by mutagenesis (Y177F)
      did not significantly change the Km value for cortisone. However, removal of the
      hydrophobic side chain by changing tyrosine to alanine (Y177A) or substitution
      with a hydrophilic side chain by changing tyrosine to glutamine (Y177Q) increased
      Km values for cortisone. These data suggest that Y177 is involved in substrate
      binding through its hydrophobic side chain but not by hydrogen bonding. In
      addition, the three mutations had little effect on the binding of the rodent
      substrate 11-dehydrocorticosterone, suggesting that Y177 does not confer
      substrate specificity. However, the same mutations reduced the affinity of the
      licorice derived 11beta-HSD1 inhibitor glycyrrhetinic acid by about 6- to 10
      fold. Interestingly, the affinity of carbenoxolone, the hemisuccinate ester of
      glycyrrhetinic acid with a similar potency against the wildtype enzyme, was not
      drastically affected by the same mutations at Y177. These data suggest that Y177
      has a unique role in inhibitor binding. Molecular modeling with glycyrrhetinic
      acid led to findings consistent with the experimental data and provided potential
      interaction mechanisms. Our data suggest that Y177 plays an important role in
      both substrate and inhibitor binding but it is unlikely a hydrogen bond donor for
      the substrate.

PMID- 16580272
TI  - Trabecular bone density of male human cervical and lumbar vertebrae.
AB  - The objective of this study was to determine the bone mineral density (BMD) of
      cervical vertebrae and correlate with the lumbar spine. Fifty-seven young adult
      healthy male volunteers, ranging from 18 to 41 years of age, underwent
      quantitative computed tomography (QCT) scanning of C2-T1 and L2-L4 vertebrae. To
      account for correlations, repeated measures techniques were used to compare data
      as a function of spinal level and region. Linear regression methods were used (+/
      95% CI) to compare data as a function of spinal level and region. The mean age
      and body height were 25.0 +/- 5.8 years and 181.0 +/- 7.6 cm. BMD decreased from
      the rostral to caudal direction along the spinal column. Grouped data indicated
      that the neck is the densest followed by the first thoracic vertebra and low back
      with mean BMD of 256.0 +/- 48.1, 194.3 +/- 44.2, and 172.2 +/- 28.4 mg/cm(3),
      respectively; differences were statistically significant. While BMD did not vary
      significantly between the three lumbar bodies, neck vertebrae demonstrated
      significant trends. The matrix of correlation coefficients between BMD and spinal
      level indicated that the relationship is strong in the lumbar (r = 0.92-0.96) and
      cervical (r = 0.73-0.92) spines. Data from the present study show that the
      trabecular bony architecture of the neck is significantly different from the low
      back. These quantitative BMD data from a controlled young adult healthy human
      male volunteer population may be valuable in establishing normative data
      specifically for the neck. From a trabecular bone density perspective, these
      results indicate that lumbar vertebrae cannot act as the best surrogates for neck
      vertebrae. Significant variations in densities among neck vertebrae, unlike the
      low back counterpart, may underscore the need to treat these bones as different
      structures.

PMID- 16580273
TI  - COL1A1 Sp1 polymorphism associates with bone density in early puberty.
AB  - Optimal acquisition of bone mass in puberty is a key determinant of the lifetime
      risk of osteoporosis and has a strong genetic basis. We investigated the
      relationship between the COL1A1 Sp1 polymorphism and BMD in early puberty, and
      how the genotypes relate to bone size and geometry as well as bone turnover and
      material properties in 247 10- to 13-year-old girls. Bone properties were
      measured using DXA, pQCT, and ultrasound. Also, serum P1NP, OC, B-ALP, and TRACP
      5b were assessed. Our results showed that girls with the TT genotype had
      significantly lower BMC and BMD of the total body, lumbar spine, and proximal
      femur, as well as BUA at the calcaneus, than those with the GT and GG genotype.
      They also had significantly lower B-ALP, as well as P1NP/TRACP 5b and (OC + B
      ALP)/TRACP 5b, compared to the others. These findings indicate that the COL1A1
      polymorphism is associated with low bone properties in early puberty and suggest
      a possible physiological effect on collagen metabolism and bone turnover. This
      information may contribute to the identification of children at risk for
      suboptimal acquisition of peak bone mass and may ultimately be of value in the
      planning of early preventive strategies for osteoporosis.

PMID- 16580274
TI  - Vital considerations for the use of vital statistics in obstetrical research.

PMID- 16580275
TI  - The use of United States vital statistics in perinatal and obstetric research.
AB  - Vital statistics data have been used to track maternal and child health in the
      United States since the early 1900s. The breadth of information collected on
      birth and death certificates coupled with advances in computer processing have
      made possible critical perinatal and obstetric research. These enhancements also
      facilitate potentially problematic uses of the same data. This commentary
      explores characteristics of the United States Vital Statistics System and
      presents some thoughts with regard to the appropriate use of these data. The
      advantages of vital statistics include representativeness and the ability to
      examine subpopulations. Limitations include possible underreporting of medical
      conditions and procedures, lack of ability to ascertain clinical intent, and the
      well-known issues with gestational age reporting. Analyses based on vital
      statistics are important in informing future clinical research projects. However,
      respecting the limitations of vital statistics data enhance their appropriate
      role in obstetric and perinatal research.

PMID- 16580276
TI  - Recurrence of hypertensive disorder in second pregnancy.
AB  - OBJECTIVE: The purpose of this study was to investigate the recurrence of
      hypertensive disorders in pregnancy with regard to the type of disorder, the
      onset of hypertension, and the modulating effect of overweight and weight gain
      between pregnancies. STUDY DESIGN: Maternity records from 896 parous women with
      hypertensive disorders in pregnancy in the first pregnancy were reviewed to
      reclassify disease status and calculate odds ratios for recurrence. RESULTS:
      Recurrence of hypertensive disorders in pregnancy occurred in 58% to 94% of
      second pregnancies, depending on first pregnancy disorder. Overweight (odds
      ratio, 1.82) and weight gain (odds ratio, 2.20) were related to recurrence among
      women with gestational hypertension. Early hypertension (<or =34 weeks of
      gestation) increased the recurrence risk for women with gestational hypertension
      (odds ratio, 1.85) and preeclampsia (odds ratio, 3.42). CONCLUSION: Recurrence of
      hypertensive disorders in pregnancy is common, but not specified by type of
      disorder in first pregnancy. Overweight and weight gain between pregnancies are
      associated with recurrent hypertensive disorders in pregnancy in women with
      gestational hypertension. Early onset of hypertension is a risk factor,
      independent of body weight.

PMID- 16580277
TI  - Preeclampsia, gestational hypertension and intrauterine growth restriction,
      related or independent conditions?
AB  - OBJECTIVE: Preeclampsia, gestational hypertension, and unexplained intrauterine
      growth restriction may have similar determinants and consequences. In this study,
      we compared determinants and perinatal outcomes associated with these obstetric
      conditions. STUDY DESIGN: We analyzed 39,615 pregnancies (data from the WHO
      Antenatal Care Trial), of which 2.2% were complicated by preeclampsia, 7.0% by
      gestational hypertension, and 8.1% by unexplained intrauterine growth restriction
      (ie, not associated with maternal smoking, maternal undernutrition, preeclampsia,
      gestational hypertension, or congenital malformations). We compared the risk
      factors associated with these groups. Fetal death, preterm delivery, and severe
      neonatal morbidity and mortality were the primary outcomes. Logistic regression
      analyses were adjusted for study site, socioeconomic status, and (if appropriate)
      birth weight and gestational age. RESULTS: Diabetes, renal or cardiac disease,
      previous preeclampsia, urinary tract infection, high maternal age, twin
      pregnancy, and obesity increased the risk of both hypertensive conditions.
      Previous large-for-age birth, reproductive tract surgery, antepartum hemorrhage
      and reproductive tract infection increased the risk for gestational hypertension
      only. Independent of maternal age, primiparity was a risk factor only for
      preeclampsia. Both preeclampsia and gestational hypertension were associated with
      increased risk for fetal death and severe neonatal morbidity and mortality.
      Mothers with preeclampsia compared with those with unexplained intrauterine
      growth restriction were more likely to have a history of diabetes, renal or
      cardiac disease, chronic hypertension, previous preeclampsia, body mass index
      more than 30 kg/cm2, urinary tract infection and extremes of maternal age.
      Conversely, unexplained intrauterine growth restriction was associated with
      higher risk of low birth weight in previous pregnancies, but not with previous
      preeclampsia. Both conditions increased the risk for perinatal outcomes
      independently but preeclampsia was associated with considerable higher risk.
      CONCLUSION: Preeclampsia and gestational hypertension shared many risk factors,
      although there are differences that need further evaluation. Both conditions
      significantly increased morbidity and mortality. Conversely, preeclampsia and
      unexplained intrauterine growth restriction, often assumed to be related to
      placental insufficiency, seem to be independent biologic entities.

PMID- 16580278
TI  - Myth of the ideal cesarean section rate: commentary and historic perspective.
AB  - Attempts to define, or enforce, an "ideal" cesarean section rate are futile, and
      should be abandoned. The cesarean rate is a consequence of individual value-laden
      clinical decisions, and is not amenable to the methods of evidence-based
      medicine. The influence of academic authority figures on the cesarean rate in the
      US is placed in historic context. Like other population health indices, the
      cesarean section rate is an indirect result of American public policy during the
      last century. Without major changes in the way health and maternity care are
      delivered in the US, the rate will continue to increase without improving
      population outcomes.

PMID- 16580279
TI  - Calcium supplementation during pregnancy and lactation: effects on the mother and
      the fetus.
AB  - Calcium consumption is essential for bone development and maintenance throughout
      life, yet more than one half of the female population in the United States does
      not consume the recommended amount of calcium. Calcium intake is especially
      crucial during pregnancy and lactation because of the potential adverse effect on
      maternal bone health if maternal calcium stores are depleted. There is often a
      transient lowered bone mineral density and increased rate of bone resorption,
      with the greatest consequence during the third trimester and throughout
      lactation. Studies indicate that calcium consumption should be encouraged,
      especially during pregnancy and lactation, to replace maternal skeletal calcium
      stores that are depleted during these periods. Because the fetus in utero and the
      neonate through breast-feeding are dependent on maternal sources for the total
      calcium load, adequate maternal calcium intake also can affect fetal bone health
      positively. Proper calcium consumption can be attained through the diet by the
      consumption of dairy products or leafy greens (such as kale), the consumption of
      fortified foods, or by supplementation with widely available calcium-containing
      supplement products. Because many women experience heartburn during pregnancy,
      calcium-based antacids are ideal for providing heartburn relief, and they offer a
      calcium supplement to ensure maternal and fetal bone health, without the danger
      of adverse effects on the neonate.

PMID- 16580281
TI  - Associations between fetal inherited thrombophilia and adverse pregnancy
      outcomes.
AB  - OBJECTIVE: The purpose of this study was to investigate associations between
      fetal inherited thrombophilia and adverse pregnancy outcomes, including pregnancy
      induced hypertensive disorders (PIHD), antepartum hemorrhage (APH), small-for
      gestational age <10th percentile (SGA), and preterm birth (PTB). STUDY DESIGN:
      Seven hundred and seventeen cases and 609 controls were genotyped for Factor V
      Leiden (FVL, G1691A), Prothrombin gene mutation (PGM, G20210A), and
      Methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C using DNA from
      newborn screening cards. RESULTS: For babies born <28 weeks' gestation, PGM was
      associated with an increased risk of SGA (OR 6.40, 95%CI 1.66-24.71) and APH with
      SGA (OR 6.35, 95%CI 1.63-24.75). Homozygous MTHFR A1298C was associated with an
      increased risk of SGA for babies born 28-31 weeks gestation (OR 4.00, 95%CI 1.04
      15.37), and with APH and SGA for babies born <32 weeks' gestation (OR 3.57, 95%CI
      1.09-11.66). Homozygous MTHFR C677T was associated with a reduced risk of PTB and
      SGA (OR 0.52, 95%CI 0.28-0.96) for babies born 32 to 36 weeks' gestation.
      Homozygous FVL decreased the risk of PTB <32 weeks' gestation (OR 0.55, 95%CI
      0.31-0.98). CONCLUSION: Fetal thrombophilic polymorphisms may be related to
      adverse pregnancy outcomes, in particular SGA.

PMID- 16580282
TI  - Antepartum vaginal bleeding, fetal exposure to oral pathogens, and risk for
      preterm birth at <35 weeks of gestation.
AB  - OBJECTIVE: The purpose of this study was to determine the risks for fetal
      exposure to oral pathogens and the relationship between vaginal bleeding and
      fetal exposure in preterm birth risk. STUDY DESIGN: An analysis of prospectively
      collected data for the longitudinal Oral Conditions and Pregnancy Study was
      conducted. Maternal factors that potentially were associated with fetal exposure
      to oral pathogens (defined as detection of umbilical cord serum Immunoglobulin M
      to 1 of 5 oral pathogens) were examined, and the role of vaginal bleeding and
      fetal exposure to oral pathogens in preterm birth risk was explored. Preterm
      birth was defined as delivery at <35 weeks of gestation. An adjusted relative
      risk (95% CI) for fetal exposure was calculated. Adjusted hazard ratios (95% CI)
      were calculated for preterm birth among women whose data were stratified by the
      presence/absence of bleeding and/or fetal exposure to oral pathogens. RESULTS:
      There were complete data for 661 women; 230 women (34.8%) with and 431 women
      (65.2%) without fetal exposure to oral pathogens. In multivariable analysis,
      first- or second-trimester bleeding and white race were associated significantly
      with fetal exposure to oral pathogens (adjusted relative risk, 1.8 [95% CI, 1.3
      2.5] and 1.3 [95% CI, 1.1-1.7], respectively). The adjusted hazard ratio for
      preterm birth among women with first- or second-trimester bleeding and fetal
      exposure to oral pathogens was 6.4 (95% CI: 2.6-16.0). CONCLUSION: Vaginal
      bleeding is associated with fetal exposure to oral pathogens, which increases
      preterm birth risk. Whether bleeding is the cause of or result of fetal exposure
      to oral pathogens remains to be determined.

PMID- 16580283
TI  - Selective serotonin reuptake inhibitors and adverse pregnancy outcomes.
AB  - OBJECTIVE: The purpose of this study was to assess the safety of the use of
      selective serotonin reuptake inhibitors in pregnancy. STUDY DESIGN: We carried
      out a retrospective cohort study of 972 pregnant women who had been given at
      least 1 selective serotonin reuptake inhibitor prescription in the year before
      delivery and 3878 pregnant women who did not receive selective serotonin reuptake
      inhibitors and who were matched by the year of the infant's birth, the type of
      institute at birth, and the mother's postal code from 1990 to 2000 in the
      Canadian province of Saskatchewan. RESULTS: The risks of low birth weight
      (adjusted odds ratio, 1.58; 95% CI, 1.19, 2.11), preterm birth (adjusted odds
      ratio, 1.57; 95% CI, 1.28, 1.92), fetal death (adjusted odds ratio, 2.23; 95% CI,
      1.01, 4.93), and seizures (adjusted odds ratio, 3.87; 95% CI, 1.00, 14.99) were
      increased in infants who were born to mothers who had received selective
      serotonin reuptake inhibitor therapy. CONCLUSION: The use of selective serotonin
      reuptake inhibitors in pregnancy may increase the risks of low birth weight,
      preterm birth, fetal death, and seizures.

PMID- 16580284
TI  - Oral analgesia compared with intravenous patient-controlled analgesia for pain
      after cesarean delivery: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to determine whether oral analgesia with
      oxycodone-acetaminophen or a patient-controlled analgesia device with morphine
      provides superior analgesia after cesarean delivery. STUDY DESIGN: Ninety-three
      patients with scheduled cesarean delivery were assigned randomly to receive
      either oral analgesia with oxycodone-acetaminophen or a morphine patient
      controlled analgesia device. At 6 and 24 hours after the procedure, pain was
      assessed on a visual analog pain scale of 0 to 10. Nausea, sedation, pruritus,
      ambulation, emesis, and oral fluid intake were also assessed. RESULTS: Patients
      who used oral analgesia without a patient-controlled analgesia device experienced
      less pain at 6 and 24 hours after cesarean delivery. They also had less nausea
      and drowsiness at 6 hours but slightly more nausea at 24 hours. CONCLUSION: Oral
      analgesia with oxycodone-acetaminophen may offer superior pain control after
      cesarean delivery with fewer side-effects as compared with morphine patient
      controlled analgesia. Consideration should be given to expanding the use of oral
      analgesia in patients immediately after cesarean delivery.

PMID- 16580285
TI  - Hypoalbuminemia: a cause of fetal hydrops?
AB  - OBJECTIVE: The pathophysiology of fetal hydrops is still unclear. One factor that
      is believed to contribute to hydrops is hypoalbuminemia. Our research question
      was whether hypoalbuminemia in immune hydrops is causative or a secondary effect.
      STUDY DESIGN: Between 1987 and 2005, fetal blood samples were taken at the first
      fetal blood transfusion in 224 Rh-D alloimmunized pregnancies. We measured
      hemoglobin concentration and albumin concentration and assessed the severity of
      hydrops. RESULTS: A decrease in albumin concentration occurred only below a
      hemoglobin deficit of >8 SDs in 27 fetuses. In 161 nonhydropic, 44 mildly
      hydropic, and 19 severely hydropic fetuses, albumin concentrations were >2 SDs
      below the mean for gestational age in 6%, 14%, and 63%, respectively. CONCLUSION:
      Our finding that most fetuses with immune hydrops have an albumin concentration
      within the normal range (71%) suggests that hypoalbuminemia is unlikely to cause
      the initial development of immune hydrops.

PMID- 16580286
TI  - Tocolysis in women with preterm labor between 32 0/7 and 34 6/7 weeks of
      gestation: a randomized controlled pilot study.
AB  - OBJECTIVE: The purpose of this study was to determine whether intravenous
      magnesium sulfate (MgSO4) followed by oral nifidepine tocolysis in women with
      preterm labor between 32 0/7 and 34 6/7 weeks' gestation reduces neonatal
      hospital stay. STUDY DESIGN: Fifty-four women between 32 0/7 and 34 6/7 weeks
      with preterm labor were randomized to receive either MgSO4 and oral nifidepine (n
      = 24) or no tocolysis (n = 30). All women received betamethasone and prophylactic
      antibiotics. The primary outcome was total neonatal hospital stay. Data were
      analyzed using Chi-square and Mann Whitney U test. RESULTS: The 2 groups had
      similar mean cervical dilation and gestational age at enrollment. There were no
      statistically significant differences in total neonatal hospital stay (5.8 +/-
      7.2 days; median of 3 days in the no tocolysis vs. 7.5 +/- 8.6 days; median of 3
      days in the tocolysis group), rate of preterm delivery (57% vs. 75%) or need for
      oxygen supplementation (7% vs. 21%, p < 0.23). The neonatal complications were
      similar in each group. CONCLUSION: Tocolysis after 32 weeks gestation does not
      reduce neonatal hospital stay.

PMID- 16580287
TI  - Surgical management of twin reversed arterial perfusion sequence.
AB  - OBJECTIVE: The purpose of this study was to review our experience in the
      management of twin reversed arterial perfusion sequence to derive management
      recommendations. STUDY DESIGN: All patients with twin reversed arterial perfusion
      sequence who were seen for consultation between 1993 and 2004 were studied.
      Criteria for umbilical cord occlusion included abdominal circumference of the
      twin reversed arterial perfusion fetus that was more than or equal to the pump
      twin, polyhydramnios (maximum vertical pocket > or = 8 cm), abnormal Doppler
      studies or hydrops of the pump twin, or monoamniotic twins. Various surgical and
      access techniques for umbilical cord occlusion were used as they were developed.
      RESULTS: Seventy-four patients with twin reversed arterial perfusion sequence
      were studied. Sixty-five patients were considered surgical candidates, of which
      51 patients underwent umbilical cord occlusion attempt. The overall perinatal
      survival for surgical candidates who had umbilical cord occlusion was 65% (33/51
      patients) versus 42.9% (6/14 patients) for the surgical candidates who did not
      undergo umbilical cord occlusion (P = .1). However, perinatal outcomes in
      surgical patients were significantly better than expectantly treated surgical
      candidates if the dividing membrane was not disrupted purposely (22/28 patients;
      78.5%; P = .02). Surgery within the sac of the twin reversed arterial perfusion
      fetus was feasible in 23.5% of patients and was associated with no incidence of
      premature rupture of membranes, with 83% perinatal survival, and with a
      significantly greater gestational age at delivery (36 weeks). There were no
      significant differences in perinatal outcome relative to the specific surgical
      technique that was used. CONCLUSION: Surgical management of twin reversed
      arterial perfusion sequence is indicated in high-risk patients. The surgical
      approach and the surgical technique should be tailored to the specific clinical
      presentation, preferably by performing the surgery within the sac of the twin
      reversed arterial perfusion sequence fetus and avoiding disruption of the
      dividing membrane.

PMID- 16580288
TI  - Accuracy of obstetric diagnoses and procedures in hospital discharge data.
AB  - OBJECTIVE: The objective of the study was to estimate the validity of obstetric
      procedures and diagnoses in California patient discharge data. STUDY DESIGN: We
      randomly sampled 1611 deliveries from 52 of 267 California hospitals that
      performed more than 678 eligible deliveries in 1992 to 1993. We compared hospital
      reported procedures and diagnoses against our recoding of the same records.
      RESULTS: Cesarean, forceps, and vacuum delivery were accurately reported, with
      sensitivities and positive predictive values exceeding 90%. Episiotomy was
      underreported (70% sensitivity). Cesarean indications were reported with at least
      60% sensitivity, except uterine inertia, herpes, and long labor. Among
      comorbidities, sensitivity exceeded 60% for chorioamnionitis, diabetes, premature
      labor, preeclampsia, and intrauterine death. Sensitivity was poor (less than 60%)
      for anemia, asthma, thyroid disorders, mental disorders, drug abuse,
      genitourinary infections, obesity, fibroids, excessive fetal growth,
      hypertension, premature rupture, polyhydramnios, and postdates. CONCLUSION: The
      validity of hospital-reported obstetric procedures and diagnoses varies, with
      moderate to high accuracy for some codes but poor accuracy for others.

PMID- 16580289
TI  - Is planned vaginal delivery for breech presentation at term still an option?
      Results of an observational prospective survey in France and Belgium.
AB  - OBJECTIVE: A large trial published in 2000 concluded that planned vaginal
      delivery of term breech births is associated with high neonatal risks. Because
      the obstetric practices in that study differed from those in countries where
      planned vaginal delivery is still common, we conducted an observational
      prospective study to describe neonatal outcome according to the planned mode of
      delivery for term breech births in 2 such countries. STUDY DESIGN: Observational
      prospective study with an intent-to-treat analysis to compare the groups for
      which cesarean and vaginal deliveries were planned. Associations between the
      outcome and planned mode of delivery were controlled for confounding by
      multivariate analysis. The main outcome measure was a variable that combined
      fetal and neonatal mortality and severe neonatal morbidity. The study population
      consisted of 8105 pregnant women delivering singleton fetuses in breech
      presentation at term in 138 French and 36 Belgian maternity units. RESULTS:
      Cesarean delivery was planned for 5579 women (68.8%) and vaginal delivery for
      2526 (31.2%). Of the women with planned vaginal deliveries, 1796 delivered
      vaginally (71.0%). The rate of the combined neonatal outcome measure was low in
      the overall population (1.59%; 95% CI [1.33-1.89]) and in the planned vaginal
      delivery group (1.60%; 95% CI [1.14-2.17]). It did not differ significantly
      between the planned vaginal and cesarean delivery groups (unadjusted odds ratio =
      1.10, 95% CI [0.75-1.61]), even after controlling for confounding variables
      (adjusted odds ratio = 1.40, 95% CI [0.89-2.23]). CONCLUSION: In places where
      planned vaginal delivery is a common practice and when strict criteria are met
      before and during labor, planned vaginal delivery of singleton fetuses in breech
      presentation at term remains a safe option that can be offered to women.

PMID- 16580290
TI  - The "PRIM" study: a randomized comparison of prostaglandin E2 gel with the nitric
      oxide donor isosorbide mononitrate for cervical ripening before the induction of
      labor at term.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy and safety
      profile of prostaglandin E2 with isosorbide mononitrate for cervical ripening
      before the induction of labor at term. STUDY DESIGN: Primigravid women were
      assigned randomly to receive either 40 mg of isosorbide mononitrate or 2 mg of
      prostaglandin E2. Efficacy outcomes were the cervical ripening effect of each
      agent and the time from treatment initiation to delivery. Safety outcomes were
      the incidence and frequency of maternal side effects and events that would be
      potentially hazardous for mother and baby during outpatient cervical ripening.
      RESULTS: Prostaglandin E2 was more effective than isosorbide mononitrate in
      inducing a change in modified Bishop score. Mean duration from treatment
      initiation to delivery was greater for isosorbide mononitrate than prostaglandin
      E2. There were no adverse events in the isosorbide mononitrate group that would
      contraindicate outpatient treatment. However, in the prostaglandin E2 group, 7%
      of the pregnancies had abnormal fetal heart rate patterns (P = .0002). Maternal
      satisfaction was significantly higher in the isosorbide mononitrate group.
      CONCLUSION: Although isosorbide mononitrate was less effective, maternal
      satisfaction was significantly greater. The safety profile of each agent was such
      that it would be reasonable to give isosorbide mononitrate, but not prostaglandin
      E2, on an outpatient basis.

PMID- 16580291
TI  - Intravaginal glyceryl trinitrate and dinoprostone for cervical ripening and
      induction of labor.
AB  - OBJECTIVE: This study was undertaken to evaluate the efficacy and safety of
      intravaginal administration of glyceryl trinitrate plus dinoprostone versus
      dinoprostone, for cervical ripening and induction of labor. STUDY DESIGN: A
      prospective, double-blind, placebo-controlled, randomized clinical trial was
      conducted among 196 singleton low-risk nullipara women with term pregnancies and
      unfavorable cervices who were randomly assigned to receive intravaginal glyceryl
      trinitrate plus dinoprostone or placebo plus dinoprostone. The main outcome
      variables were time from application to active phase of labor and to delivery.
      Secondary outcomes were change in Bishop score, fetal and maternal morbidity, and
      incidence of cesarean deliveries. RESULTS: The interval from application of the
      initial dose to the beginning of active phase of labor was 868 +/- 582 and 1136
      +/- 692 minutes (P = .004) and from initial dose to delivery was 1339 +/- 826 and
      1620 +/- 975 minutes (P = .03) for the glyceryl trinitrate and placebo groups,
      respectively. There were no significant differences in Bishop score change,
      cesarean section rate, and in the incidence of hypersystole and hyperstimulation.
      The incidence of tachysystole was significantly lower in the glyceryl trinitrate
      group (4% vs 15%, P < or = .02). No maternal and neonatal adverse effects were
      noted. CONCLUSION: The association of glyceryl trinitrate with dinoprostone is
      more effective than dinoprostone alone for labor induction in low-risk patients
      at term with unfavorable cervices.

PMID- 16580292
TI  - Peripartum myocardial ischemia: a review of Canadian deliveries from 1970 to
      1998.
AB  - OBJECTIVE: The purpose of this study was to evaluate the incidence of peripartum
      myocardial ischemia in Canada. STUDY DESIGN: We identified the cohort of women
      who were admitted to Canadian hospitals for delivery between 1970 and 1998 to
      calculate the incidence rate and to evaluate potential risk factors. RESULTS: One
      hundred fourteen of 10,032,375 women delivered in Canadian hospitals between 1970
      and 1998 had peripartum myocardial ischemia recorded as a discharge diagnosis.
      The overall crude incidence rate was 1.1 (95% confidence interval 0.93, 1.37)
      women with peripartum myocardial ischemia per 100,000 women delivering per year
      as noted in the Canadian Hospital Morbidity database. Rates did not increase over
      time but increased with maternal age. Identified risk factors were diabetes
      mellitus, hyperlipidemia, and chronic heart disease. The case fatality rate among
      women with the disease was 1.8%. CONCLUSION: The incidence of peripartum
      myocardial ischemia did not increase between 1970 and 1998 in Canada, despite an
      aging cohort with more prevalent medical comorbidities. Maternal mortality from
      this event is lower than previously described.

PMID- 16580293
TI  - Serum sFlt1 concentration during preeclampsia and mid trimester blood pressure in
      healthy nulliparous women.
AB  - OBJECTIVE: The purpose of this study was to determine whether serum fms-like
      tyrosine kinase 1 (sFlt1) concentration during preeclampsia were associated with
      mid trimester blood pressure, other maternal characteristics, or pregnancy
      outcomes. STUDY DESIGN: We performed a nested case-control study within the
      Calcium for Preeclampsia Prevention study cohort. Each woman with preeclampsia
      (case) was matched to 1 normotensive control. A total of 120 pairs of women was
      chosen randomly. Serum concentrations of sFlt1 and placental growth factor were
      measured throughout pregnancy, but before labor and delivery. We focused on data
      from 40 women with blood specimens that were obtained after the onset of
      preeclampsia. After logarithmic transformation, we determined mean serum sFlt1
      concentrations of all control specimens within gestational age windows during
      which case specimens had been obtained after the onset of preeclampsia. Within
      each of these gestational age windows, we computed an upper bound for the control
      specimens equal to 2 standard deviations above the mean. After the onset of
      preeclampsia, 16 women with log-transformed serum sFlt1 values greater than the
      upper bound of the control specimens were considered to have high preeclampsia
      serum sFlt1 levels. The 24 other women were considered to have low preeclampsia
      serum sFlt1 levels. RESULTS: Women with high or low concentrations of serum sFlt1
      during preeclampsia (arithmetic means, 5746 and 3007 pg/mL, respectively) had
      similar pregnancy outcomes and similar maternal characteristics, except for blood
      pressure at Calcium for Preeclampsia Prevention study enrollment. Systolic and
      diastolic blood pressure at enrollment at 13 to 21 weeks of gestation were
      significantly higher in the 24 women with low serum sFlt1 concentrations during
      preeclampsia (systolic blood pressure, 114 mm Hg; diastolic blood pressure, 65 mm
      Hg) than in the 16 women who had preeclampsia at high serum sFlt1 concentrations
      (systolic blood pressure, 106 mm Hg; diastolic blood pressure, 59 mm Hg). Blood
      pressure at 13 to 21 weeks among the women with high preeclampsia serum sFlt1
      concentrations was identical to the blood pressure among normotensive control
      subjects. In linear regression analyses of data from all 40 women, both systolic
      (P < .0001) and diastolic (P = .014) blood pressures at enrollment were
      correlated negatively with natural logarithm serum sFlt1 concentration after
      onset of preeclampsia. CONCLUSION: Women with higher mid trimester blood pressure
      had preeclampsia at lower serum sFlt1 concentrations. Because higher blood
      pressure may reflect occult endothelial damage, these observations may explain
      increased susceptibility to preeclampsia among women with pre-existing vascular
      disease.

PMID- 16580294
TI  - Customized versus population-based birth weight standards for identifying growth
      restricted infants: a French multicenter study.
AB  - OBJECTIVE: This study was undertaken to describe the characteristics of
      pregnancies according to a customized definition of fetal growth restriction and
      to determine the association between customized standards and adverse pregnancy
      outcomes. STUDY DESIGN: Two definitions of growth restriction, a population and a
      customized standard, were applied to 56,606 births in 5 tertiary maternity
      hospitals in France from 1997 to 2002. The customized definition was adjusted for
      maternal height and weight, parity, fetal gender, and gestational age. Odds
      ratios and 95% CIs for neonatal morbidity and mortality were calculated to
      compare small for gestational age and non-small for gestational age births.
      RESULTS: By using customized standards, 2.7% of births were reclassified as small
      for gestational age. These births were to taller, heavier, multiparous women.
      Compared with non-small for gestational age births, these newly detected small
      for-gestational-age newborn infants showed an increased risk of stillbirth (odds
      ratio = 4.52, 95% CI 2.47-8.14) and perinatal death (odds ratio = 2.60, 95% CI
      1.62-4.15). These infants were also more likely to be born to women with
      hypertensive disease in pregnancy (7.0%) versus those reclassified as non-small
      for gestational age (2.3%) and those non-small for gestational age by both
      standards (5.5%). CONCLUSION: These findings highlight the interest of using
      customized birth weight standard adjusted for maternal and neonatal
      characteristics to identify fetuses at risk, particularly among apparently normal
      fetuses. Individual growth norms should be used to define small for gestational
      age.

PMID- 16580295
TI  - Maternal vasculopathy and histologic diagnosis of preeclampsia: poor correlation
      of histologic changes and clinical manifestation.
AB  - OBJECTIVE: The purpose of this study was to evaluate the frequency of maternal
      vasculopathy and to determine the usefulness of placental examination in
      correlation with clinical manifestation of pregnancy-induced hypertension. STUDY
      DESIGN: We investigated 350 pregnancy-induced hypertension placentas over a 2.5
      year period (January 2002-June 2004) to identify the potential usefulness of the
      maternal vasculopathy in histologic diagnosis and corroboration of clinical
      preeclampsia. This study was carried out at West Virginia University Ruby
      Memorial Hospital, where 1271 placentas were examined macroscopically and
      microscopically for the period. The presence or absence of vascular changes,
      infarctions, thrombosis, abruption, chorangiosis, and chorioamnionitis were
      investigated for each placenta with the clinical diagnosis of preeclampsia or
      pregnancy-induced hypertension. RESULTS: Two types of vascular changes that are
      characteristic of pregnancy-induced hypertension, namely maternal atherosis and
      fibrinoid medial necrosis, were found in 21.4% of the placentas (75/350
      placentas). These vascular changes were found mainly in the decidua capsularis of
      the membrane rolls, not on the decidua basalis of the maternal floor. There were
      more placental infarctions within these placentas (32.3%; 113/350 placentas).
      Intervillous thrombosis was 18.9% (66/350 placentas); microscopic abruption was
      6.3% (22/350 placentas); chorangiosis was 10.9% (38/350 placentas), and
      chorioamnionitis was 8.6% (30/350 placentas). CONCLUSION: These findings
      demonstrate that the maternal vascular changes that are characteristic of
      pregnancy-induced hypertension are found in approximately 1 of 5 pregnancy
      induced hypertension placentas. Examination of pregnancy-induced hypertension
      placentas should be based on a combination of a number of histologic changes.
      Furthermore, the decidua capsularis of the fetal membrane roll, rather than the
      decidua basalis of the maternal floor, of the placenta should be examined for
      these maternal vascular changes.

PMID- 16580296
TI  - Cerebral hemodynamics during the induction of antenatal periventricular
      leukomalacia by hemorrhagic hypotension in chronically instrumented fetal sheep.
AB  - OBJECTIVE: Our purpose was to determine the characteristics of cerebral ischemia
      during the induction of antenatal periventricular leukomalacia by hemorrhagic
      hypotension in premature fetal sheep. STUDY DESIGN: The hemorrhage group received
      an acute withdrawal of 40% of the fetoplacental blood volume (n = 7), whereas an
      isovolemic exchange transfusion was performed in the control group (n = 7).
      Changes in the total hemoglobin, oxy-hemoglobin, and deoxy-hemoglobin levels in
      the cerebral tissue were assessed with the use of near-infrared spectroscopy and
      compared statistically. RESULTS: Of 7 fetuses in the hemorrhage group, 5
      exhibited periventricular leukomalacia but none in the control group (P < .05).
      In the hemorrhage group, both brain total-hemoglobin and deoxy-hemoglobin
      decreased seriously after insult, and the decreased levels persisted even after
      recovery of systemic blood pressure, whereas such drastic changes were not
      observed in the control group, suggesting the occurrence of reperfusion failure
      in the fetal brain in the hemorrhage group. CONCLUSION: The no-reflow phenomenon
      and successive reperfusion injuries after cerebral ischemia could be closely
      involved in the induction of antenatal periventricular leukomalacia in this
      experimental condition.

PMID- 16580297
TI  - To the Point: reviews in medical education online computer assisted instruction
      materials.
AB  - Computer technology is rapidly changing the way educators can interact with their
      students. This article reviews the research regarding the integration of online
      computer-assisted instructional materials into medical education.

PMID- 16580299
TI  - Presidential address: the art of discovery.

PMID- 16580298
TI  - Diagnosis of inferior vermian hypoplasia by fetal magnetic resonance imaging:
      potential pitfalls and neurodevelopmental outcome.
AB  - OBJECTIVE: Advances in fetal magnetic resonance imaging allow the detection of
      subtle anatomic anomalies of unclear long-term clinical significance. The purpose
      of this study was to examine the accuracy of fetal magnetic resonance imaging in
      the diagnosis of isolated inferior vermian hypoplasia and to describe the
      neurodevelopmental outcome. STUDY DESIGN: We reviewed all cases with fetal and
      postnatal magnetic resonance imaging studies between 1999 and 2003 and identified
      19 cases with a diagnosis of isolated inferior vermian hypoplasia. We compared
      prenatal and postnatal magnetic resonance imaging studies and evaluated subjects
      using developmental scales. RESULTS: Isolated inferior vermian hypoplasia was
      confirmed by postnatal magnetic resonance imaging in 68% of the patients (13/19);
      the remaining 6 patients had normal postnatal magnetic resonance imaging results.
      On developmental testing at mean age 19.8 +/- 4.9 months, 3 infants (23%) with
      confirmed postnatal diagnosis demonstrated motor and language delays and
      functional difficulties, and 2 infants (15%) had behavioral problems; none of the
      infants with normal postnatal magnetic resonance imaging studies were delayed.
      CONCLUSION: Isolated inferior vermian hypoplasia in the second trimester may be
      over-diagnosed by fetal magnetic resonance imaging and therefore warrants
      postnatal magnetic resonance imaging confirmation.

PMID- 16580300
TI  - Human fetal growth and organ development: 50 years of discoveries.
AB  - Knowledge about human fetal growth and organ development has greatly developed in
      the last 50 years. Anatomists and physiologists had already described some
      crucial aspects, for example, the circulation of blood during intrauterine life
      through the fetal heart, the liver as well as the placenta. However, only in the
      last century physiologic studies were performed in animal models. In the human
      fetus, the introduction of ultrasound and Doppler velocimetry has provided data
      about the growth and development of the fetus and of the circulation through the
      different fetal districts. Moreover, in the last 2 decades we have learned about
      fetal oxygenation and fetal nutrient supply caused by the availability of fetal
      blood samples obtained under relatively steady state conditions. These studies,
      together with studies using stable isotope methodologies, have clarified some
      aspects of the supply of the major nutrients for the fetus such as glucose, amino
      acids, and fatty acids. At the same time, the relevance of placental function has
      been recognized as a major determinant of fetal diseases leading to intrauterine
      growth restriction. More recently, the availability of new tools such as 3
      dimensional ultrasound and magnetic resonance imaging, have made possible the
      evaluation of the growth and development of fetal organs. This knowledge in the
      healthy fetus will improve the ability of clinicians to recognize abnormal
      phenotypes of the different fetal organs, thus allowing to stage fetal diseases.

PMID- 16580301
TI  - An autoregulatory element maintains HOXA10 expression in endometrial epithelial
      cells.
AB  - OBJECTIVE: HOXA10 is necessary for endometrial receptivity and regulated by sex
      steroids. Secretory phase HOXA10 expression increases in endometrial epithelial
      cells, despite the loss of progesterone receptor. Stromal-epithelial molecular
      communication likely transmits progesterone signaling from progesterone receptor
      containing stromal cells to epithelium. Here we investigated an alternative
      hypothesis, persistent HOXA10 expression by autoregulation. STUDY DESIGN: Nested
      segments of the HOXA10 5' regulatory region were cloned into a pGL3-Luciferase
      reporter construct and tested for HOXA10-induced reporter activity. Direct
      binding was assayed by electrophoretic mobility shift assay. RESULTS: One 370
      base pair element drove reporter gene expression specifically in response to
      HOXA10 in Ishikawa cells but not in BT-20 cells. This element contained a site
      that bound HOXA10 protein. CONCLUSION: HOXA10 expression is driven by an
      autoregulatory element in the 5' regulatory region of the gene. Autoregulation is
      a novel alternative molecular mechanism by which steroid-induced gene expression
      can be maintained in the absence of steroid receptors.

PMID- 16580304
TI  - The effects of the inhibition of inducible nitric oxide synthase on angiogenesis
      of epithelial ovarian cancer.
AB  - OBJECTIVE: The release of nitric oxide by tumor cells, through the stimulation of
      inducible nitric oxide synthase expression, may play a critical role in ovarian
      cancer progression. In this study we have sought to determine the effects of
      inhibiting inducible nitric oxide synthase on angiogenesis that was induced by 2
      ovarian cancer cell lines, SKOV and MDAH2774. STUDY DESIGN: Real-time polymerase
      chain reaction and enzyme-linked immunosorbent assay techniques were used to
      determine the expression levels of inducible nitric oxide synthase and vascular
      endothelial growth factor in the ovarian cancer cell lines in response to
      treatments with L-NAME, an inhibitor of nitric oxide synthase, and SNAP, and
      nitric oxide donor. Ovarian cancer-induced angiogenesis was assessed in vitro
      with an established assay that is based on the ability of human umbilical vein
      endothelial cells to form a tubular network in response to angiogenic agents.
      RESULTS: SKOV and MDAH2774 cell lines exhibited over-expression of inducible
      nitric oxide synthase and have high baseline nitric oxide levels. This was
      associated with high levels of vascular endothelial growth factor production and
      angiogenesis induction. Treatment of the ovarian cancer cell lines with L-NAME
      significantly reduced vascular endothelial growth factor levels production and
      completely inhibited angiogenesis. In contrast, treatment with SNAP significantly
      increased vascular endothelial growth factor levels and increased angiogenesis in
      both cell lines. CONCLUSION: Our data suggest that the inhibition of inducible
      nitric oxide synthase may form a basis for a novel therapeutic treatment option
      for ovarian cancer therapy.

PMID- 16580310
TI  - Immunocytochemical evidence for the presence and location of the neurotrophin-Trk
      receptor family in adult human preovulatory ovarian follicles.
AB  - OBJECTIVE: This study was undertaken to evaluate the presence or absence of
      neurotrophins and their respective receptors within adult human preovulatory
      follicles. STUDY DESIGN: Prospective study of neurotrophins and their receptors
      in follicular cells and unfertilized oocytes from women undergoing aspiration for
      in vitro fertilization/intracytoplasmic sperm injection. Cells (mural and cumulus
      granulosa cells, unfertilized oocytes) were examined for immunocytochemical
      staining of neurotrophin and receptor proteins. RESULTS: Mural and cumulus
      granulosa cells were positive for BDNF, NT-4/5, NT-3, and NGF, as well as for Trk
      B, Trk C, and Trk A receptors. Unfertilized oocytes were positive for Trk B, Trk
      C, and Trk A receptors. CONCLUSION: Neurotrophins and their respective receptor
      proteins are present within the mural and cumulus granulosa cells of adult human
      preovulatory follicles. Neurotrophin receptors are present in human unfertilized
      oocytes. The location of the neurotrophins and their receptors suggest both an
      autocrine and paracrine function within the adult human ovarian follicle.

PMID- 16580307
TI  - Biologic targets for therapeutic intervention in endometrioid endometrial
      adenocarcinoma and malignant mixed mullerian tumors.
AB  - OBJECTIVE: The purpose of this study was to investigate the AKT signaling cascade
      in endometrial cancers and to assess its therapeutic potential. STUDY DESIGN:
      Western blotting and immunohistochemistry were used to investigate the expression
      of estrogen receptor, progesterone receptor, HER2, AKT, and 4EBP1 proteins in 27
      atrophic endometria, 31 grade 1 and 24 grade 3 endometrioid endometrial cancers,
      and 19 malignant mixed mullerian tumors. Inhibition of the AKT signaling cascade
      was investigated in cell lines. RESULTS: Malignant mixed mullerian tumors and
      grade 3 endometrioid endometrial cancers demonstrated higher levels of AKT and
      4EBP1 activation and hormone receptor loss compared with grade 1 endometrioid
      endometrial cancers and atrophic samples. HER2 over-expression was identified
      most often in grade 3 tumors without gene amplification. In endometrial cancer
      cell-lines, AKT cascade inhibitors decreased cell proliferation by apoptosis and
      cell cycle arrest. CONCLUSION: AKT cascade activation in grade 3 endometrioid
      endometrial cancers and malignant mixed mullerian tumors is a novel finding.
      Apoptosis and growth arrest that results from AKT inhibition expose opportunities
      for therapeutic intervention.

PMID- 16580313
TI  - The use of needle biopsy for assessment of placental gene expression.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that placental
      samples that are obtained by needle aspiration ex vivo are useful for the
      determination of villus gene expression. STUDY DESIGN: Placental biopsy was
      performed with a spinal needle after uncomplicated deliveries. Villi were
      inspected microscopically, and RNA was extracted and analyzed with capillary
      electrophoresis. Gene expression was determined with quantitative polymerase
      chain reaction. RESULTS: We obtained more placental villous fragments per
      aspiration using a 20-gauge needle (5.2 +/- 1.8 fragments) than with a 22-gauge
      needle (3.3 +/- 1.6 fragments; P < .01). RNA quality was adequate, based on the
      28S and 18S recombinant RNA bands, with a mean 260/280 ratio of 1.88. The amount
      of extracted RNA correlated with the number of villous fragments per aspirate.
      Importantly, the expression of NDRG1 and hPL, both markedly altered in hypoxia,
      was consistent between villi that were obtained by either needle or standard
      biopsy. CONCLUSION: Placental samples that are obtained by ex vivo needle
      aspiration are useful for the extraction of RNA and for the determination of
      villous gene expression.

PMID- 16580316
TI  - Maternal-fetal surgery for myelomeningocele: neurodevelopmental outcomes at 2
      years of age.
AB  - OBJECTIVE: This study was undertaken to examine short-term neurodevelopmental
      outcomes in children with myelomeningocele (MMC) who underwent in utero
      neurosurgical closure. STUDY DESIGN: Between 1998 and 2002, 51 fetuses underwent
      in utero MMC closure at our Center. Thirty (63%) of these children have returned
      for neurodevelopmental testing at 2 years of age using the Bayley Scales of
      Infant Development and Preschool Language Scales. RESULTS: Overall shunt rate was
      43% in this group. Neurodevelopmental testing found 67% with cognitive language
      and personal-social skills in the normal range, 20% with mild delays, and 13%
      with significant delays. Children with shunted hydrocephalus scored lower than
      those with unshunted ventriculomegaly. CONCLUSION: Children who have undergone
      fetal MMC closure have characteristic neurodevelopmental deficits that do not
      appear worsened by fetal surgery, and developmental outcomes may be improved by
      decreasing the need for ventriculoperitoneal shunting.

PMID- 16580319
TI  - Learning enhancement with neuropeptides.
AB  - OBJECTIVE: Previous work has demonstrated that two synthetic peptides can prevent
      prenatal alcohol-induced damage as assessed by prevention of learning
      abnormalities in adult offspring as well as improve outcome from traumatic brain
      damage. The current studies were undertaken to evaluate whether these peptides
      could enhance performance in a learning and memory paradigm when administered
      either prenatally or to aged mice. STUDY DESIGN: For prenatal treatment, C57Bl6/J
      mice were treated on gestational day 8 with 1 oral administration of D-NAP or D
      SAL alone or D-NAP+D-SAL or a double dose of D-SAL. Control groups were same
      regimen treated with vehicle alone. Learning was assessed in adult male offspring
      (35-50 days) by using the Morris water maze. To evaluate aged animals, 12-month
      old mice were treated with D-NAP and D-SAL or vehicle alone daily and tested on
      the Morris water maze. RESULTS: Offspring exposed prenatally to D-NAP+D-SAL
      learned significantly faster than controls, with an earlier onset of learning and
      an overall decreased latency to find the hidden platform (P < .05). Animals
      exposed prenatally to either D-NAP or D-SAL alone learned similar to control,
      with a trend toward faster latencies. Aged animals who received D-NAP+D-SAL
      learned significantly faster than age-matched controls, with an earlier onset of
      learning (P < .05). CONCLUSION: Combined D-NAP+D-SAL enhanced learning in healthy
      young mice and aged mice. These findings suggest potential therapeutic
      interventions not only during a critical developmental period, but also in aged
      animals.

PMID- 16580322
TI  - A multifacited approach to improve patient safety, prevent medical errors and
      resolve the professional liability crisis.
AB  - The current professional liability crisis is the third in the last 30 years.
      Similarities of the 3 crises are the rising cost of professional liability
      insurance and a diminishing number of sources available to purchase coverage.
      Proposed tort reform with caps on noneconomic damages and attorney contingency
      fees is a back end approach and will do little to solve this crisis or prevent
      future ones. The current situation can only be solved by placing an increased
      emphasis on improving patient safety and elimination of all preventable medical
      errors. A national electronic medical record must be developed and rapid response
      teams need to be available in most hospitals. The protective devices of
      privileged communication and peer review are counterproductive and must be
      eliminated. Full and prompt disclosure of any medical error or injury needs to be
      made. Physicians must be taught proper communication skills and the importance of
      teamwork. Providers with frequent patient, nursing or medical staff complaints
      must be critically reviewed. The present system of risk management needs to move
      from a reactive position to a role of being proactive for both patient and
      physician. Claims management should offer the patient early compensation when
      appropriate and pursue a vigorous defense when medical care is adequate. Experts
      should be identified who will render fair, unbiased reviews of medical care with
      all of their findings being disclosed. Similar experts need to devise clear,
      concise, evidenced based standards of care for common medical conditions.

PMID- 16580325
TI  - Risk factors for previable premature rupture of membranes or advanced cervical
      dilation: a case control study.
AB  - OBJECTIVE: The purpose of this study was to identify risk factors for second
      trimester premature preterm rupture of membranes or advanced cervical dilation in
      a high-risk population. STUDY DESIGN: A retrospective case control study was
      performed that compared women with premature preterm rupture of membranes or
      advanced cervical dilation to term control subjects. The cases included all
      singleton pregnancies between 14 and 24 weeks of gestation with premature preterm
      rupture of membranes or advanced cervical dilation between 1996 and 2000. The
      next 2 term deliveries were chosen as control subjects. The variables compared
      between cases and control subjects included pregnancy history, infectious and
      medical histories, cervical/uterine procedures, and habits. This study had
      institutional review board approval. RESULTS: There were 102 women with premature
      preterm rupture of membranes, 56 women with advanced cervical dilation, and 316
      control subjects. The mean gestational ages for premature preterm rupture of
      membranes or advanced cervical dilation were 20 +/- 2.6 and 19.9 +/- 2.6 weeks.
      Tobacco use, history of or current cervical incompetence, previous second
      trimester delivery, previous termination at <20 weeks of gestation, and previous
      premature preterm rupture of membranes were associated significantly with
      premature preterm rupture of membranes or advanced cervical dilation compared
      with term control subjects. When controlled for parity, age, marital status, and
      race, these variables remained significant. Bacterial vaginosis in current
      pregnancy was associated significantly with only advanced cervical dilation but
      not premature preterm rupture of membranes compared with control subjects. A
      history of Chlamydia was most common in the term control subjects (19.6%).
      CONCLUSION: In a high-risk population of inner city women, only pregnancy history
      and tobacco use distinguished women with second trimester premature preterm
      rupture of membranes or advanced cervical dilation from term control subjects. No
      infectious risk factors distinguished control women from women with premature
      preterm rupture of membranes. The only modifiable risk identified was tobacco
      use.

PMID- 16580328
TI  - Are women with recurrent spontaneous preterm births different from those without
      such history?
AB  - OBJECTIVE: This study was undertaken to determine whether women with recurrent
      spontaneous preterm births (rSPBs) have different clinical characteristics or
      systemic markers than those with isolated preterm (iSPBs) or recurrent term
      births (rTBs), when assessed remote from delivery. STUDY DESIGN: We compared
      clinical characteristics and findings (including cervical ultrasound, bacterial
      vaginosis, fetal fibronectin), maternal plasma markers obtained at 22 to 24
      weeks' gestation (inflammatory cytokines, cortisol, and corticotrophin-releasing
      hormone), between women with rSPBs (2 or 3 consecutive SPBs and no TBs), iSPBs (1
      SPB and 1 or 2 TBs), and rTBs (2 or 3 consecutive TBs and no SPBs). RESULTS: A
      total of 1257 women met our inclusion criteria; 47 rSPBs, 241 iSPBs (80 current
      and 161 prior iSPBs), and 969 rTBs. Before pregnancy, women with rSPBs had lower
      weights (P < .0001) and body mass indexes (BMIs) (P < .001), and were more likely
      to be less than 100 lbs (P = .008) or less than 19.8 kg/m2 BMI (P = .001). At 22
      to 24 weeks those with rSPBs remained lighter and leaner, and had more advanced
      Bishop scores than iSPBs and rTBs. Ultrasound demonstrated progressive decrease
      in cervical length for those with rTBs, prior iSPBs, current iSPBs, and rSPBs,
      and also progressively more frequent short cervixes with worsening history (P <
      .001). Cervical length was shorter for women of lower pregravid weight and BMI,
      but not with shorter height. At 22 to 24 weeks, women with rSPBs had more common
      uterine contractions and tocolytic agents, but not more infections or antibiotic
      therapy. Those with an SPB in the current gestation had higher fetal fibronectin
      levels and more frequent vaginal bleeding, regardless of prior outcome. Maternal
      cortisol and corticotrophin-releasing hormone were higher in women with iSPBs and
      rSPBs than in rTB controls, (P = .001 and .0027), a finding more apparent with
      SPB in the current pregnancy. However, maternal cytokines were not increased with
      either iSPBs or rSPBs. CONCLUSION: Women with rSPBs are leaner, contract more,
      have shorter cervixes, and have more advanced Bishop scores than women with iSPBs
      or rTBs.

PMID- 16580331
TI  - Usefulness of preoperative lymphoscintigraphy in patients who undergo radical
      hysterectomy and pelvic lymphadenectomy for cervical cancer.
AB  - OBJECTIVE: The purpose of this study was to assess the value of preoperative
      lymphoscintigraphy before intraoperative lymphatic mapping for sentinel lymph
      node identification during radical hysterectomy. STUDY DESIGN: Fifty patients
      underwent intraoperative lymphatic mapping on our institutional review board
      approved protocol. The location of sentinel lymph nodes that were found on
      lymphoscintigraphy and intraoperative lymphatic mapping were compared. RESULTS:
      Fifteen of 21 patients (71%) with solitary sentinel lymph nodes that were found
      on lymphoscintigraphy had multiple sentinel lymph node basins found during the
      operation. Thirteen of 25 patients (52%) with unilateral sentinel lymph node
      basins that were found on lymphoscintigraphy had bilateral sentinel lymph nodes
      at intraoperative lymphatic mapping. Of 15 patients with 2 sentinel lymph node
      locations that were identified on lymphoscintigraphy, 12 patients (80%) had > or
      = 3 found during the operation. Of the sentinel lymph nodes that were located on
      the external iliac basin (n = 47) on lymphoscintigraphy, only 20 lymph nodes
      (43%) were found at that location during the operation. Concordance between the 2
      methods was poor. Seven of the 9 patients with lymph node metastases had disease
      that was limited to the sentinel lymph nodes. CONCLUSION: Preoperative
      lymphoscintigraphy adds little value over intraoperative lymphatic mapping for
      sentinel lymph node identification during radical hysterectomy.

PMID- 16580334
TI  - The hemoglobin, oxygen, carbon dioxide and hydrogen ion concentrations in the
      umbilical blood of sheep and goats as sampled via indwelling plastic catheters.
      1965.

PMID- 16580336
TI  - Indwelling plastic catheters in developmental physiology.

PMID- 16580337
TI  - Safety of influenza vaccination during pregnancy.

PMID- 16580339
TI  - Neonatal Escherichia coli sepsis: possible effects of gender, type of surfactant,
      or time to initiation of antibiotics?

PMID- 16580341
TI  - Cyclooxygenase-2, angiogenesis, tumor cell proliferation, P-glycoprotein in
      advanced ovarian serous carcinoma.

PMID- 16580343
TI  - Benign gynecologic conditions in Tamoxifen-treated patients.

PMID- 16580345
TI  - Polymorphisms of the glucocorticoid receptor gene and major depression.
AB  - BACKGROUND: The most consistent biological finding in patients with depression is
      a hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis, which might be
      caused by impaired glucocorticoid signaling. Glucocorticoids act through the
      glucocorticoid receptor (GR) for which several polymorphisms have been described.
      The N363S and BclI polymorphisms have been associated with hypersensitivity to
      glucocorticoids, whereas the ER22/23EK polymorphism is related to glucocorticoid
      resistance. METHODS: We studied whether the susceptibility to develop a
      depression is related to these polymorphisms by comparing depressive inpatients
      (n = 490) and healthy control subjects (n = 496). Among depressed patients, we
      also investigated the relation between GR variants and dysregulation of the HPA
      axis, as measured by the combined dexamethasone suppression/corticotropin
      releasing hormone (CRH)-stimulation test, clinical response to antidepressive
      treatment, and cognitive functioning. RESULTS: Homozygous carriers of the BclI
      polymorphism and ER22/23EK-carriers had an increased risk of developing a major
      depressive episode. We found no genetic associations with functional HPA-axis
      measures in depressed patients. The ER22/23EK-carriers, however, showed a
      significantly faster clinical response to antidepressant therapy as well as a
      trend toward better cognitive functioning during depression. CONCLUSIONS: The
      BclI and ER22/23EK polymorphisms were associated with susceptibility to develop
      major depression. In addition, the ER22/23EK polymorphism is associated with a
      faster clinical response to antidepressant treatment. These findings support the
      notion that variants of the GR gene might play a role in the pathophysiology of a
      major depression and can contribute to the variability of antidepressant
      response.

PMID- 16580346
TI  - ERK1/2 pathway is involved in the inhibitory effect of crocetin on angiotensin II
      induced vascular smooth muscle cell proliferation.
AB  - Angiotensin II (Ang II) induces vascular smooth muscle cells (VSMCs)
      proliferation, which plays an important role in the development and progression
      of atherosclerosis. Ang II-induced cellular events have been implicated, in part,
      in the activation of extracellular signal-regulated kinases 1/2 (ERK1/2).
      Crocetin is a natural carotenoid compound isolated from Gardenia jasminoids
      Ellis. In the present study, we investigated the effect of crocetin on the Ang II
      induced VSMCs proliferation and ERK1/2 activation. 3-[4,5-dimethylthiazol-2-yl]
      2,5-dephenyl tetrazolium bromide (MTT) and [3H]thymidine incorporation assay
      showed that the Ang II-induced VSMCs proliferation was inhibited significantly by
      crocetin. In-gel kinase assay indicated that Ang II elicited rapid and
      significant increase of ERK1/2 activity in VSMCs, which was suppressed by
      crocetin markedly. Western blotting analysis and cell-based enzyme-linked
      immunosorbent assay (ELISA) demonstrated that crocetin significantly inhibited
      the phosphorylation and activation of ERK1/2 induced by Ang II. Using the
      indirect immunofluorescent technique, we also found that crocetin inhibited
      nuclear translocation of activated ERK1/2 induced by Ang II. These findings
      suggest that the suppression by crocetin of the Ang II-induced VSMCs
      proliferation can be attributed, at least in part, to its inhibitory effect on
      ERK1/2 pathway.

PMID- 16580347
TI  - Poor response--the devil is in the definition.

PMID- 16580349
TI  - Different perceptions of similar observations.

PMID- 16580351
TI  - Predictive value of myomectomy.

PMID- 16580353
TI  - Registries for anti-adhesion products?

PMID- 16580355
TI  - Induction of ovulation and ovarian cancer: a critical review of the literature.
AB  - OBJECTIVE: To critically examine the possible association between ovulation
      inducing drugs and ovarian cancer. DESIGN: Medline literature review and cross
      reference of published data. RESULTS(S): The studies that have adjusted for the
      effects of confounding factors such as duration of oral contraceptive use and
      number of pregnancies have noted an increased risk of ovarian cancer among
      infertile women who remain childless despite long periods of unprotected
      intercourse. Whether such women are at risk due to the primary basis for their
      infertility or factors such as ovulation-inducing drugs, has been the subject of
      several studies. Overall, the findings on ovarian cancer (especially invasive
      epithelial and non-epithelial) risk associated with fertility drug treatment are
      reassuring. However, a stronger association between fertility drug use and
      borderline tumors of the ovary has been observed. CONCLUSION(S): Despite the
      overall reassuring findings of the available studies, there is a need for well
      designed clinical trials to understand the possible carcinogenic effects of the
      ovulation-inducing drugs.

PMID- 16580356
TI  - Confocal microscopic analysis of the spindle and chromosome configurations of
      human oocytes matured in vitro.
AB  - OBJECTIVE: To assess the potential effects of in vitro maturation (IVM) of human
      oocytes on the meiotic spindle and associated chromosome configuration. DESIGN:
      Prospective study. SETTING: Hospital-based IVF center. PATIENT(S): Patients with
      polycystic ovary syndrome (PCOS) undergoing unstimulated and stimulated cycles of
      oocyte retrieval. INTERVENTION(S): Immature (germinal vesicle and metaphase I)
      and mature (metaphase II) oocytes were collected from PCOS patients. The meiotic
      spindle and chromosome configurations in oocytes matured in vitro and in vivo
      were studied by confocal microscopy, with fluorescent labeling techniques for
      visualization of both microtubules and chromatin. MAIN OUTCOME MEASURE(S):
      Meiotic spindle and associated chromosome configurations. RESULT(S): Oocytes can
      develop to the metaphase II stage after IVM. Confocal microscopic observations
      revealed that the oocytes matured in vitro had a higher frequency of abnormal
      meiotic spindle and chromosomal alignment morphology than in vivo-matured
      oocytes. These abnormalities included a partial or total disorganization of the
      meiotic spindle microtubules. Abnormal chromosome organization included dispersal
      of chromosomes or chromosomes with an aberrant, less-condensed appearance. The
      proportions of abnormality in spindle and chromosome configurations in oocytes
      matured in vitro were 43.7% and 33.3%, respectively, which was significantly
      higher than in those oocytes matured in vivo (13.6% and 9.1%). CONCLUSION(S): In
      vitro maturation can have deleterious effects on the organization of the meiotic
      spindle and chromosome alignment of human oocytes. This result suggests one
      possible explanation for the reduced developmental potential of oocytes matured
      in vitro compared with those matured in vivo. This is likely a contributing
      factor to the overall lower clinical outcomes observed after IVM and ET.

PMID- 16580357
TI  - The in vitro maturation (IVM) of human oocytes for in vitro fertilization (IVF):
      is it time yet to switch to IVM-IVF?
AB  - The recent study by Li et al. observed that human oocytes from patients with
      polycystic ovary syndrome (PCOS) matured in vitro exhibited a higher proportion
      of abnormal spindle structures and disturbed chromosomal configurations compared
      with in vivo-matured oocytes from a control group of PCOS patients. This article
      discusses the obstacles that must be overcome and factors that must be monitored
      when attempting to optimize conditions for the in vitro maturation of human
      oocytes, with particular attention to the strengths and weaknesses of the study
      by Li et al.

PMID- 16580358
TI  - Developmental potential of in vitro- and in vivo-matured human oocytes collected
      from stimulated and unstimulated ovaries.
AB  - The study by Li and coworkers demonstrated that human oocytes collected from the
      unstimulated ovary have high rates of meiotic spindle and chromosome
      abnormalities. Until improvements can be made to culture conditions, in vitro
      maturation protocols for patient treatment should be considered experimental.

PMID- 16580359
TI  - Spindle abnormalities in oocytes.
AB  - Human oocytes have been found to exhibit spindle abnormalities that might lead to
      chromosomal errors when matured in vitro. However, the immature oocytes recovered
      from patients with polycystic ovary syndrome might include a high proportion of
      oocytes from degenerating and atretic follicles that are not selected for
      maturation in vivo.

PMID- 16580360
TI  - Assessing the quality of oocytes derived from in vitro maturation: are we looking
      under the lamppost?
AB  - Oocytes are complex cells comprising many cellular systems, each of which is
      essential for proper oocyte function. Methods to assess the diverse and critical
      cellular systems in oocytes derived from in vitro maturation are badly needed.

PMID- 16580363
TI  - Arab Americans, African Americans, and infertility: barriers to reproduction and
      medical care.
AB  - OBJECTIVE: To compare barriers to infertility care among African Americans and
      Arab Americans. DESIGN: Qualitative study using semi-structured reproductive
      histories and open-ended ethnographic interviews. SETTING: Infertile volunteers
      in a private IVF clinic in Dearborn, Michigan, an Arab American ethnic enclave
      community in metropolitan Detroit. PATIENT(S): Arab American men presenting for
      infertility diagnosis and treatment, including assisted reproductive
      technologies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Perceived barriers
      to effective infertility care. RESULT(S): Arab Americans and African Americans
      living in metropolitan Detroit are at increased risk of infertility and share
      similar histories of poverty, racism, and cultural barriers to medical treatment.
      This study, which focused on infertile Arab American men living in or near
      Dearborn (an ethnic enclave community composed mainly of recent immigrants and
      war refugees), revealed significant barriers to effective infertility care,
      including economic constraints, linguistic and cultural barriers, and social
      marginalization in mainstream U.S. society, particularly after September 11,
      2001. CONCLUSION(S): Arab Americans experience disparities in access to
      infertility care, largely because of poverty and social marginalization in post
      September 11th America.

PMID- 16580364
TI  - Explaining disparities in treatment seeking: the case of infertility.
AB  - OBJECTIVE: To present an integrated model of help-seeking, review empirical work
      in its support, and show its application to the explanation of racial and ethnic
      disparities in infertility help-seeking. DESIGN: Review. SETTING: None.
      PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None.
      RESULT(S): None. CONCLUSION(S): A help-seeking model provides a plausible
      explanation of observed disparities in infertility help-seeking. In addition to
      being related to income, race and ethnicity is related to prior experience with
      doctors, marital status, parity, knowledge and attitudes toward reproductive
      technology, and attitudes supporting spiritual rather than technological
      solutions to health problems.

PMID- 16580365
TI  - Health disparities and infertility: impacts of state-level insurance mandates.
AB  - OBJECTIVE: To determine whether important racial, ethnic, or socioeconomic status
      (SES) health disparities exist in infertility, impaired fecundity, or infertility
      treatment. DESIGN: Four waves of the National Survey of Family Growth (NSFG) were
      pooled. Measures were compared across various race/ethnicity, education, and age
      groups. PARTICIPANT(S): Data for 31,047 women 15-44 years old from the NSFG were
      pooled. INTERVENTION(S): Outcomes were compared by whether the women's states of
      residence had a mandate in place (at least 1 year before the interview) to compel
      insurers to cover or offer to cover infertility treatment. MAIN OUTCOME
      MEASURE(S): Infertility status, impaired fecundity, ever having sought
      infertility treatment. RESULT(S): Infertility is more common for non-Hispanic
      black women, non-Hispanic other race women, and Hispanic women than for non
      Hispanic white women, and both infertility and impaired fecundity are more common
      for high school dropouts and high school graduates with no college than for 4
      year college graduates, and for older women compared with women 29 and younger.
      Older women, non-Hispanic white women, and women who are more educated (with at
      least some college) are more likely to have ever received treatment. No evidence
      has been found that the racial, ethnic, or education disparities are ameliorated
      by the health insurance mandates. CONCLUSION(S): Racial, ethnic, and educational
      disparities exist in infertility status and treatment, and educational
      disparities in impaired fecundity. More study of the impact of infertility
      treatment mandates on these disparities is needed.

PMID- 16580366
TI  - Natural hair color and the incidence of endometriosis.
AB  - OBJECTIVE: To investigate a previously hypothesized relation between natural hair
      color and endometriosis. DESIGN: Prospective cohort study. SETTING: Nurses'
      Health Study II with 10 years of follow-up. PARTICIPANT(S): A total of 90,065
      women, 25-42 years old, who had never been diagnosed with endometriosis,
      infertility, or cancer at baseline in 1989. MAIN OUTCOME MEASURE(S): Incidence of
      laparoscopically confirmed endometriosis according to natural hair color.
      RESULT(S): During 379,422 person-years of follow-up, 1,130 cases of
      laparoscopically confirmed endometriosis were reported among women with no past
      infertility. After adjusting for age, calendar time, parity, race, and body mass
      index at age 18, we observed no association overall. However, compared with women
      with any other hair color, we observed an increased rate of endometriosis among
      women with naturally red hair who had never been infertile (incidence rate = 1.3,
      95% confidence interval [CI] = 1.0-1.7), but a decreased rate among women with
      naturally red hair among women who were infertile (incidence rate = 0.4, 95% CI =
      0.2-1.2); P value, test for heterogeneity = .03. CONCLUSION(S): Overall, we did
      not observe a significant relation between red hair color and the rate of
      endometriosis, however this prospective cohort study suggests that the relation
      may differ by infertility status.

PMID- 16580367
TI  - International disparities in access to infertility services.
AB  - OBJECTIVE: To characterize the international availability of infertility
      services. DESIGN: A PubMed computer search to identify relevant articles.
      SETTING: Academic medical center. PATIENT(S): None. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): None. RESULT(S): Epidemiological data suggests that
      approximately 80 million people worldwide are infertile. Most countries in the
      industrial west have declining fertility rates marked by late marriage, postponed
      childbearing, and primary infertility. In contrast, in the developing world,
      there is little voluntary effort to postpone childbearing and early first
      marriage is common. However, a high prevalence of sexually transmitted infections
      and infections acquired as a result of inadequate health care result in increased
      rates of secondary infertility. In developing societies, childlessness is often
      highly stigmatized and leads to profound social suffering for infertile women in
      particular, yet most infertile people in the developing world have virtually no
      access to effective treatment. Internationally, a minority of countries offer
      IVF, and even where it is available, on average it is prohibitively expensive and
      utilized by a fraction of those who could benefit from its use. CONCLUSION(S):
      Wide disparities exist in the quality, availability, and delivery of infertility
      services between the developed and developing nations of the world.

PMID- 16580368
TI  - Socioeconomic and racial disparities among infertility patients seeking care.
AB  - OBJECTIVE: To examine sociodemographic differences based on patient
      race/ethnicity among infertility patients seeking care in a state with mandated
      coverage of infertility treatment. DESIGN: Cross-sectional survey. SETTING:
      University-hospital-based fertility center. PATIENT(S): A total of 1,500
      consecutive women who presented for infertility care. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Self-report questionnaire assessing patient race/ethnicity,
      diagnosis, income, education level, and duration of infertility before seeking
      care. RESULT(S): African American women experienced a significantly longer
      duration of infertility before seeking care compared with Caucasian women (4.3
      vs. 3.3 years, respectively; P=.03). With regard to infertility diagnosis, a
      significantly greater proportion of African American and Hispanic women had tubal
      factor infertility compared with Caucasian women (24.0% and 27.3% vs. 5.3%,
      respectively; P=.001). Looking at the highest level of education attained by
      patients, a significantly greater proportion of African American and Hispanic
      women had less than a 4-year college degree compared with Caucasian women (48%
      and 40.9% vs. 13.2%, respectively; P<.001). Examining the gross annual household
      income of patients, a significantly greater proportion of African American and
      Hispanic women had household incomes below $100,000 compared with Caucasian women
      (72% and 68.2% vs. 37.3%, respectively; P<.01). CONCLUSION(S): African American
      women are more likely to seek infertility treatment after a longer duration of
      failed conception compared with Caucasian women. Furthermore, African American,
      and Hispanic women are more likely to have tubal factor infertility, a lower
      education level, and a lower household income compared with Caucasian women.

PMID- 16580369
TI  - Infertility among low-income Latinos.
AB  - OBJECTIVE: To explore the experience of infertility among low-income Latinos.
      DESIGN: Ethnographic qualitative interview study. SETTING: Academic research
      environment. PATIENT(S): One hundred eighteen Latinos who sought medical care for
      infertility. INTERVENTION(S): Tape-recorded interviews with 88 women and 30 men
      were transcribed and analyzed for emergent themes. MAIN OUTCOME MEASURE(S):
      Cultural beliefs regarding fertility and infertility, the value placed on having
      children, access to and use of health care resources, and non-biomedical
      approaches to having children. RESULT(S): Latino women and men believed that
      children were the basis of the marital relationship and that childless marriages
      were considered a failure. No couples had the economic resources to pursue
      medical treatment beyond a basic level. A difference was found in approaches to
      infertility treatment between women raised in the United States and those raised
      elsewhere, with those raised in the United States being more assertive in seeking
      care. Women frequently saw practitioners of Western biomedicine and humoral
      medicine. Women reported that they would continue trying to conceive until they
      reached menopause. CONCLUSION(S): Infertility is a devastating experience for
      Latinos that has far-reaching effects, both on women and men individually and on
      the couple relationship.

PMID- 16580370
TI  - Comparison of assisted reproductive technology utilization and outcomes between
      Caucasian and African American patients in an equal-access-to-care setting.
AB  - OBJECTIVE: Racial disparity in assisted reproductive technology (ART) outcomes
      has been reported but remains controversial. Reasons for the disparity are
      unclear, and access to care has been suggested as a causative factor. In this
      study, we sought to examine minority utilization of ART in the Department of
      Defense (DoD) compared with minority utilization in the U.S. ART population.
      Outcomes from ART were compared between Caucasian (Cau) and African American (AA)
      patients, and etiologies of disparity were examined. DESIGN: Retrospective cohort
      study. SETTING: University-based ART program. PATIENT(S): A total of 1,457
      patients undergoing first-cycle fresh, nondonor ART. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Clinical pregnancy rate, live birth rate, implantation rate,
      spontaneous abortion rate. RESULT(S): Within the DoD population, AA women had a
      fourfold increase in utilization of ART services relative to the U.S. ART
      population. In this equal-access-to-care setting, AA women experienced a
      clinically significant decrease in live birth rate that did not reach statistical
      significance (29.6% vs. 35.8%, risk ratio [RR] 0.83, 95% confidence interval [CI]
      0.67-1.02) and a statistically significant increase in spontaneous abortions
      compared with Cau women (25% vs. 15.9%, RR 1.57, 95% CI 1.05-2.36). This might be
      explained, in part, by a higher prevalence of uterine leiomyomas in AA women
      (30.8% AA vs. 10.7% Cau, RR 2.85, 95% CI 2.06-3.95). For both AA and Cau women,
      the presence of fibroids at baseline ultrasound was associated with reductions in
      clinical pregnancy rates (35% with leiomyomas vs. 43.2% without leiomyomas, RR
      0.74, 95% CI 0.51-0.98), live birth rates (26.2% vs. 36.0%, RR 0.63, 95% CI 0.44
      0.90), and implantation rates (25.6% vs. 31.1% RR 0.82, 95% CI 0.69-0.98).
      CONCLUSION(S): Utilization of ART services among AA women increased when access
      to care was improved. A clinically significant reduction in live birth rate and
      statistically significant increase in spontaneous abortion rate was observed in
      AA women compared with Cau women. Leiomyomas were three times more prevalent in
      AA women and reduced ART success, regardless of race. The persistence of racial
      differences in an equal-access-to-care environment might be explained, in part,
      by the increased prevalence of leiomyomas in AA women.

PMID- 16580372
TI  - Effect of reduced oocyte aging on the outcome of rescue intracytoplasmic sperm
      injection.
AB  - OBJECTIVE: To evaluate the results of a novel protocol that allows to rescue IVF
      unfertilized oocytes by intracytoplasmic sperm injection (ICSI). DESIGN:
      Prospective clinical trial. SETTING: Private reproductive medical center.
      PATIENT(S): Thirty patients undergoing IVF. INTERVENTION(S): Controlled ovarian
      stimulation (COS), conventional IVF, rescue ICSI, embryo culture, and embryo
      transfer. MAIN OUTCOME MEASURE(S): Identification of unfertilized IVF oocytes 6
      hours after insemination and fertilization, and developmental rates of those
      oocytes after rescue microinjection, as well implantation and pregnancy rates
      (PR). RESULT(S): All oocytes (392) from 30 patients were inseminated with
      standard IVF 3 hours after ovum pick-up. Polar body (PB) status was checked at
      decumulation and rechecked 3 hours later. Eighty-two oocytes were fertilized
      after IVF alone and 184 nonactivated oocytes (failed fertilization) were rescue
      microinjected and 166 of them fertilized (20 patients). Cleavage stage on day 2
      was significantly more advanced and embryo grade was higher after standard IVF
      fertilization than after rescue ICSI. Eight of the 30 embryos transferred were
      implanted in the IVF-only patients (27%) and 8 of 68 embryos in the rescue ICSI
      patients (12%). CONCLUSION(S): Rescue ICSI of unfertilized IVF oocytes 6 hours
      after insemination (9 hours after egg retrieval) can provide normal
      fertilization, embryo development, and pregnancy; however, corresponding outcome
      parameters tend to be impaired in comparison to the standard IVF fertilization
      results.

PMID- 16580371
TI  - Impact of assisted hatching on the outcome of intracytoplasmic sperm injection: a
      prospective, randomized clinical trial and pregnancy follow-up.
AB  - OBJECTIVE: To evaluate the overall effect of assisted hatching (AH) on the
      implantation, pregnancy, and live birth rates in women undergoing
      intracytoplasmic sperm injection (ICSI) cycles; and to determine the effect of AH
      on the cytogenetic outcome (chromosomal constitution) of pregnancy. DESIGN:
      Prospective, randomized study. SETTING: Academic research environment.
      PATIENT(S): A total of 172 couples were enrolled in the study. INTERVENTION(S):
      Assisted hatching was carried out on day-3 ICSI embryos. MAIN OUTCOME MEASURE(S):
      Implantation, clinical pregnancy, and live birth rates; cytogenetic analysis of
      abortuses and umbilical cord blood samples from newborns. RESULT(S): Biochemical,
      clinical, and ongoing pregnancy rates were not significantly different between
      the AH and control groups. The implantation rate was higher in the AH group than
      in the control group (16% vs. 8%), especially in women aged > or =35 years.
      Postnatal umbilical cord blood samples were collected and cytogenetically
      analyzed from 39 live births (20 from the AH group, 19 from the control group).
      Two abnormal karyotypes were found (one AH, one control). There were seven
      spontaneous losses during the study interval. Six of the abortuses underwent
      cytogenetic study (five AH, one control), and four were found to have an abnormal
      karyotype (three AH, one control). CONCLUSION: We found that AH improves
      implantation rates of ICSI cycles and seems to be most effective in women aged >
      or =35 years. A larger sample size is needed to determine whether AH improves the
      take-home-baby rate. Assisted hatching did not affect the rate of chromosomal
      abnormalities in live births in this study.

PMID- 16580373
TI  - Very low-birth-weight-infants conceived by in vitro fertilization are not at
      higher risk for mortality and morbidity: a population-based study.
AB  - OBJECTIVE: To determine whether excess mortality, neonatal morbidity, and
      congenital malformations occurred in in vitro fertilization (IVF) conceived
      compared with naturally conceived singleton, twin and triplet very low birth
      weight (VLBW) infants. DESIGN: Population-based observational study from 1995
      through 2002. SETTING: Israel National VLBW infant database. PATIENT(S): A total
      of 8,181 VLBW infants conceived naturally or by IVF were stratified into groups
      of singletons and complete sets of twins and triplets. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Neonatal mortality and morbidity. RESULT(S): In the
      unadjusted analyses, mortality and neonatal morbidity rates were generally
      similar between the IVF-conceived and the naturally conceived infants stratified
      by plurality groups. When adjusted for multiple confounding variables, no excess
      neonatal mortality or morbidity occurred among IVF-conceived infants. The risk
      for congenital malformations adjusted for ethnicity, maternal age, and parity was
      also not increased in the IVF-conceived groups. CONCLUSION(S): In our population,
      VLBW infants conceived by IVF were not at increased risk for congenital
      malformations, postnatal morbidity, or mortality when compared with naturally
      conceived infants.

PMID- 16580374
TI  - Effect of coasting on cycle outcome during in vitro
      fertilization/intracytoplasmic sperm injection cycles in hyper-responders.
AB  - OBJECTIVE: To investigate the effect of coasting on IVF outcome in GnRH agonist
      cycles. DESIGN: Retrospective analysis. SETTING: Private IVF center. PATIENT(S):
      Infertile couples undergoing IVF/intracytoplasmic sperm injection (ICSI)
      treatment (normal responders [control], hyper-responders [coasting] groups).
      INTERVENTION(S): Coasting to reduce the risk of ovarian hyperstimulation syndrome
      (OHSS) among hyper-responders. MAIN OUTCOME MEASURE(S): Stimulation, embryology
      parameters, and pregnancy rate (PR). RESULT(S): The average length of coasting
      was 2.2 days. Age and baseline FSH were comparable to control cycles. There were
      more follicles and oocytes in the coasting group, but the number of fertilized
      oocytes and embryos transferred were similar. Implantation rate (22.4% vs. 13.9%)
      was higher in the control group but the PRs were comparable (45.1% vs. 38.5%).
      Within the coasting group, baseline, stimulation, and embryology parameters were
      comparable between successful and unsuccessful cycles. Pregnancy rates were
      comparable after 1, 2, and 3 or more days of coasting (36.3% vs. 38.4% vs. 40%).
      Pregnancy rates were also comparable (28.5% vs. 35.7% vs. 44.4%) when groups were
      compared based on change in E2 (<25%, 25%-50%, >50%). CONCLUSION(S): Coasting for
      3 days can be used successfully in the management of the hyper-responding
      patients during IVF.

PMID- 16580375
TI  - A high number of oocytes obtained after ovarian hyperstimulation for in vitro
      fertilization or intracytoplasmic sperm injection is not associated with
      decreased pregnancy outcome.
AB  - OBJECTIVE: To investigate the possible negative effects of a strong ovarian
      response on oocyte quality. DESIGN: Retrospective study. SETTING: Tertiary
      academic center. PATIENT(S): A total of 1,894 women (IVF, n = 1,544; ICSI, n =
      350) who underwent their first ovarian stimulation cycle during the period 1995
      2002. INTERVENTION(S): Standardized controlled ovarian stimulation with urinary
      FSH or recombinant FSH after pituitary down-regulation, followed by
      IVF/intracytoplasmic sperm injection (ICSI) and ET. MAIN OUTCOME MEASURE(S):
      Fertilization rate, fraction of high-quality embryos, and implantation rate.
      RESULT(S): Using multivariate logistic regression, we analyzed the effect,
      expressed as an odds ratio (OR), of the number of oocytes obtained (i.e., ovarian
      response) on the outcome measures. No effect of the response on the ongoing
      implantation rate or fraction of high-quality embryos was observed. Both in IVF
      (OR = 0.81, 95% confidence interval [CI] 0.75-0.87) and in ICSI (OR = 0.88, 95%
      CI 0.76-1.00), a negative effect of increasing ovarian response was seen on the
      fertilization rate per oocyte obtained. However, no negative effect was observed
      on the fertilization rate per oocyte injected in ICSI (OR = 1.00, 95% CI 0.87
      1.14). The fraction of immature oocytes rises from 3.9%, in women with < or = 3
      oocytes, to 26% in women with > 20 oocytes. CONCLUSION(S): Oocytes from high
      responders contain a greater fraction of immature oocytes, but pregnancy outcome
      is not impaired.

PMID- 16580376
TI  - Effects of recombinant human luteinizing hormone supplementation on ovarian
      stimulation and the implantation rate in down-regulated women of advanced
      reproductive age.
AB  - OBJECTIVE: To evaluate the effects of recombinant human luteinizing hormone
      (rhLH) supplementation on ovarian stimulation and implantation rate in down
      regulated women of advanced reproductive age. DESIGN: Prospective randomized
      study. SETTING: University teaching hospital. PATIENT(S): A total of 120
      consecutive normogonadotropic infertile women > or = 35 years old undergoing
      their first cycle of IVF or intracytoplasmic sperm injection (ICSI) treatment.
      INTERVENTION(S): Ovarian stimulation in a long agonist protocol with a
      combination of recombinant human follicle-stimulating hormone (rhFSH) and rhLH
      (group 1, n = 60) starting on day 6 of FSH stimulation until hCG at a daily fixed
      dose of 150 IU of rhLH, or with rhFSH alone (group 2, n = 60). MAIN OUTCOME
      MEASURE(S): Ovarian stimulation characteristics, ovum retrieval, and IVF/ICSI
      outcome. RESULT(S): The mean number of intermediate (10-14 mm) and large (> 14- <
      18 mm) but not leading (> or = 18 mm) follicles was significantly lower in group
      1 on the day of hCG injection. The oocyte yield and maturity as well as the
      number of oocytes fertilized were significantly higher in group 2 than in group
      1. However, the number of patients having embryo transfer (n = 55 in both
      treatment groups), the number and quality of embryos replaced, the implantation
      rate (20.6% vs. 21.7%) and clinical pregnancy rates per embryo transfer (44% vs.
      45%) were similar in groups 1 and 2. CONCLUSION(S): The rhLH supplementation does
      not increase ovarian response and implantation rates in patients of older
      reproductive age stimulated with rhFSH under pituitary suppression for assisted
      reproductive technologies (ARTs).

PMID- 16580377
TI  - The purinergic component of human vas deferens contraction.
AB  - OBJECTIVE: To examine purinergic signaling in human vas deferens. DESIGN: To
      study contractile responses of the scrotal vas deferens. SETTING: Research
      department of a university teaching hospital. PATIENT(S): Undergoing vasectomy or
      orchidectomy (aged 27-88 years, n = 14). INTERVENTION(S): Vasectomy or
      orchidectomy. MAIN OUTCOME MEASURE(S): Strips of vas deferens were suspended in
      an organ bath and subjected to electrical stimulation to establish frequency
      response curves. These stimulations were repeated in the presence of
      pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, P2 receptor
      antagonist), prazosin (adrenergic alpha1 antagonist), and tetrodotoxin.
      Concentration-response curves were constructed to noradrenaline and the P2X
      agonists ATP and alpha,beta-methylene ATP (alpha,beta-meATP). The P2X receptor
      subtype distribution was assessed by immunohistochemistry using specific
      antibodies. RESULT(S): The response at 32 Hz in the presence of PPADS was reduced
      by 40% and in the presence of prazosin by 80%. Noradrenaline caused concentration
      dependent contractions (EC50 = 11.8 microM). Contractions to ATP and alpha,beta
      meATP (EC50 = 6.27 microM) suggested that the functional receptor was P2X1 and/or
      P2X3. However, immunohistochemistry demonstrated P2X1, but not P2X3, receptor
      immunoreactivity on the smooth muscle cells. CONCLUSION(S): This study
      demonstrated that ATP is a co-transmitter with noradrenaline in the contraction
      of the human vas deferens predominantly acting through the P2X1 receptor.

PMID- 16580378
TI  - Utrastructural analysis of asthenozoospermic ejaculates in the era of assisted
      procreation.
AB  - OBJECTIVE: To define by transmission electron microscopy (TEM) analysis, the
      prevalence of sperm tail defects of genetic origin among men suffering for a
      reduced or absent sperm motility. DESIGN: A retrospective study. SETTING:
      Andrology Clinic, University of L'Aquila, Italy. PATIENT(S): The 120 ejaculates
      of infertile men with a forward motility (FM) < or =20% were compared to 200
      ejaculates with a FM >20%. All ejaculates had a sperm vitality >50%.
      INTERVENTION(S): Some 25-50 tails were analyzed by TEM in each ejaculate. MAIN
      OUTCOME MEASURE(S): Receiver operating characteristics (ROC) analysis was applied
      by plotting the FM of cases with or without genetic tail defects detected by TEM.
      RESULT(S): The area under the ROC curve was 0.96 (95% confidence interval 0.92
      0.98). The positive predictive accuracy for genetic tail defects in ejaculates
      with 0% FM was 46%. Three of 17 cases with genetic tail defects were classified
      as false negative when TEM analysis was restricted to ejaculates with 0% FM. A FM
      < or =7%, allowed the identification of all cases with genetic tail defects.
      CONCLUSION(S): The TEM analysis identifies sperm tail defects of genetic origin
      and should be restricted to ejaculates with severe asthenozoospermia (< or =7%
      motile sperm) and sperm vitality >50%.

PMID- 16580380
TI  - High percentage of abnormal semen parameters in a prevasectomy population.
AB  - OBJECTIVE: To evaluate semen characteristics, testicular volume, and hormonal
      levels of normal fertile men requiring vasectomy for sterilization. DESIGN:
      Retrospective study. SETTING(S): Academic medical centers. PATIENT(S): A total of
      889 patients underwent a vasectomy for sterilization. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Semen volume, sperm concentration, motility, and morphology
      according to the World Health Organization (WHO); complex motion parameters
      evaluated by computer-assisted semen analyzer; FSH, LH, and T levels; and both
      testicular volumes. RESULT(S): When compared with the WHO values, 87.2% of the
      patients presented normal sperm morphology below the normal level. The other
      semen parameters (semen volume, pH, sperm concentration, and sperm motility)
      differed from the WHO parameters in 6%-32.2% of patients. Semen volume and sperm
      concentration presented a progressive increase according to the duration of
      sexual abstinence. However, patients with 5 days or more of abstinence had a
      decrease in sperm motility. Mean testicular size had the strongest correlation
      with serum FSH levels, total sperm count, and sperm concentration. CONCLUSION(S):
      Low sperm motility and morphology were found in men who request a vasectomy for
      sterilization. Semen volume and sperm concentration present a progressive
      increase and sperm motility a decrease according to the duration of sexual
      abstinence. Sperm concentration had stronger correlations with testicular size
      than did sperm quality. Therefore, the WHO normal values need to be reconsidered.

PMID- 16580379
TI  - The production of peroxynitrite by human spermatozoa may affect sperm motility
      through the formation of protein nitrotyrosine.
AB  - OBJECTIVE: To detect peroxynitrite and 3-nitrotyrosine production in human
      spermatozoa of asthenozoospermic infertile patients and normospermic donors, and
      evaluate any influence on kinetic sperm features. DESIGN: Basic study. SETTING:
      Andrology Unit, Dept of Internal Medicine and Biochemistry Institute, Polytechnic
      University of Marche, Italy. PATIENT(S): Sixty-nine infertile patients affected
      by idiopathic asthenozoospermia and 29 normal fertile donors. INTERVENTION(S): No
      therapeutic intervention was performed on patients. MAIN OUTCOME MEASURE(S):
      Production of peroxynitrite (ONOO-) and 3-nitrotyrosine by human spermatozoa;
      kinetic sperm cells parameters. RESULT(S): Normospermic fertile donors exhibited
      ONOO- concentrations significantly lower than those of asthenozoospermic
      infertile men (9.11 +/- 3.37 vs. 27.46 +/- 5.77 nmol/10(6) cells); confocal
      microscopy showed that ONOO- was more evident in spermatozoa of patients than in
      healthy donors. Moreover, a significant negative correlation was evident between
      ONOO- concentration and total sperm motility, curvilinear velocity (VCL),
      straight progressive velocity (VSL), and linearity coefficient. Finally, an
      increase was found in the nitration of the tyrosine residues in asthenozoospermic
      samples compared to controls. CONCLUSION(S): Spontaneous tyrosine nitration
      occurs in human spermatozoa. This post-translational protein modification is
      enhanced by an overproduction of peroxynitrite, which is more evident in
      asthenozoospermic infertile patients when compared with normospermic fertile
      donors. Motility parameters are negatively affected, suggesting that ONOO- may be
      involved in defective sperm function.

PMID- 16580381
TI  - Sperm harvesting and cryopreservation during vasectomy reversal is not cost
      effective.
AB  - OBJECTIVE: To determine whether sperm harvesting and cryopreservation at the time
      of vasectomy reversal is cost-effective. DESIGN: Model of actual costs and
      results at five institutions. SETTING: Multicenter study comprising five centers,
      including university hospitals and private practices. PATIENT(S): Men undergoing
      vasectomy reversal. INTERVENTION(S): We established two models for vasectomy
      reversal. The first model was sperm harvesting and cryopreservation at the time
      of vasectomy reversal. The second model was sperm harvesting at the time of IVF
      only if the patient remained azoospermic after vasectomy reversal. Vasectomy
      reversal procedures modeled included bilateral vasovasostomy and bilateral
      epididymovasostomy. The costs for each procedure at the five institutions were
      collated and median costs determined. MAIN OUTCOME MEASURE(S): Median cost of
      procedure and calculated financial comparisons. RESULT(S): The median cost of
      testicular sperm extraction/cryopreservation performed at the time of bilateral
      vasovasostomy was $1,765 (range, $1,025-$2,800). The median cost of microsurgical
      epididymal sperm aspiration or testicular sperm extraction with cryopreservation
      performed at the time of epididymovasostomy was $1,209 (range, $905-$2,488). The
      average of the median costs for percutaneous sperm aspiration or testicular sperm
      aspiration for those patients with a failed vasectomy reversal was $725 (range,
      $400-$1,455). CONCLUSION(S): Sperm retrieval with cryopreservation at the time of
      vasectomy reversal is not a cost-effective management strategy.

PMID- 16580382
TI  - Reevaluation of azoospermic factor c microdeletions using sequence-tagged site
      markers with confirmed physical positions from the GenBank database.
AB  - OBJECTIVE: To investigate microdeletions and palindrome complexes in the
      azoospermic factor (AZF) c regions of the Y chromosome, by polymerase chain
      reaction (PCR) with sequence-tagged site (STS) markers with known physical
      positions, after verification of the exact physical locations of candidate STSs
      and exclusion of those that would give ambiguous results on PCR. DESIGN:
      Retrospective STS deletion study in infertile Japanese men. SETTING: University
      hospital and reproductive clinic. PATIENT(S): A total of 410 men with
      nonobstructive azoospermia and severe oligospermia (sperm concentrations of <5 x
      10(6)/mL). INTERVENTION(S): Polymerase chain reaction was performed for all STS
      markers confirmed to be physically located in the partial AZFb and AZFc regions
      of the Y chromosome. All STSs were retrieved from the University of California at
      Santa Cruz database, and their location and specificity were verified. MAIN
      OUTCOME MEASURE(S): Presence or absence of appropriately sized PCR products.
      RESULT(S): Sixty-nine markers were retrieved, 32 of which were not specific to
      the long arm of the Y chromosome (Yq). The markers retained for test use were
      contiguous deletions classified as P1+P2 (AZFc) or P3 proximal/P1 (AZFb+c). The
      prevalence of accurately mapped microdeletions was 5.1% (21 of 410) in this
      patient population. CONCLUSION(S): Although noncontiguous deletions were
      observed, considerable confusion remained until the genome sequence was finally
      determined because many of the STSs were either repetitive sequences or
      polymorphic between individuals or races.

PMID- 16580383
TI  - Psychological assessment of the effects of treatment with phytoestrogens on
      postmenopausal women: a randomized, double-blind, crossover, placebo-controlled
      study.
AB  - OBJECTIVE: To investigate the effects of soy isoflavones on mood and cognitive
      function in postmenopausal women. DESIGN: Randomized, double-blind, cross-over,
      placebo-controlled trial. SETTING: University Hospital, Milan, Italy; A.G.UN.CO.
      Obstetrics and Gynaecology Centre, Rome, Italy. PATIENT(S): Seventy-eight
      postmenopausal women. INTERVENTION(S): We administered 60 mg/day isoflavones or
      placebo for 6 months. After a washout period of 1 month, the patients who had
      been treated with phytoestrogens received placebo, and those who previously
      received placebo were administered phytoestrogens (for 6 months). MAIN OUTCOME
      MEASURE(S): Cognitive performance and mood were assessed by a battery of tests at
      the end of each treatment period. At the end of the study, the patients were also
      asked whether they preferred the first or second treatment. RESULT(S): The 17
      scores on cognitive performance test and the 6 for mood assessments 6 showed an
      advantage for the treatment with phytoestrogens. Similarly, of the 8 visual
      analogue scales used to indicate mood, 7 improved significantly after the
      treatment with phytoestrogens. Moreover, 49 patients preferred phytoestrogens, 9
      placebo, and 18 had no preference. The preference was not related to the order of
      treatment. CONCLUSION(S): These results suggest that isoflavones may have
      positive effects on postmenopausal women improving cognitive performance and
      mood.

PMID- 16580384
TI  - Intranasal continuous combined 17 beta-estradiol/norethisterone therapy improves
      the lipid profile in healthy postmenopausal women.
AB  - OBJECTIVE: To compare the effects of continuous combined 17beta-estradiol (E2)
      plus norethisterone (acetate) [NET(A)] therapy by either intranasal or oral
      administration on the lipid profile in postmenopausal women. DESIGN: Randomized,
      double-blind, multicenter trial. SETTING: Gynecologic outpatient department.
      PATIENT(S): Two-hundred thirty-three healthy postmenopausal women.
      INTERVENTION(S): Women received continuous combined hormone therapy, either
      intranasal E2/NET (175 microg/275 microg) as a spray (n = 117) or oral E2/NETA (1
      mg/0.5 mg) as a capsule (n = 116), for 1 year. MAIN OUTCOME MEASURE(S): Fasting
      plasma concentrations of lipids and (apo)lipoproteins; and atherogenic indices at
      baseline and after 12, 24, and 52 weeks of treatment. RESULT(S): We found a
      significant (P < .001) decrease from baseline in both treatment groups in total,
      low-density lipoprotein- (LDL), high-density lipoprotein- (HDL), and HDL2
      cholesterol, in triglycerides, apolipoprotein B (apoB), and lipoprotein(a).
      Levels of HDL3-cholesterol and apolipoprotein A1 (apoA1) were transiently
      decreased in the intranasal group. In the oral group, compared with the
      intranasal group, the decrease was larger for ratio total and LDL-cholesterol and
      lipoprotein(a) and smaller for triglycerides and apoA1. In the oral group, the
      ratios total/HDL cholesterol and LDL/HDL cholesterol were lowered, and the ratio
      apoB/LDL was increased, more than in the intranasal group. CONCLUSION(S): Both
      intranasal and oral E2/NET(A) therapy improved the lipid profile of healthy
      postmenopausal women, with some effects being more pronounced after oral
      administration.

PMID- 16580385
TI  - Digitized assessment of mammographic breast density in patients who received low
      dose intrauterine levonorgestrel in continuous combination with oral estradiol
      valerate: a pilot study.
AB  - OBJECTIVE: To perform a pilot study of the effects on the breast by low-dose
      intrauterine progestogen combined with estrogen. DESIGN: A prospective pilot
      study. SETTING: University hospital. PATIENT(S): Twenty postmenopausal women
      without any previous breast disorder. INTERVENTION(S): Women were treated with a
      low-dose intrauterine system releasing 20 microg/24 hours of levonorgestrel in
      continuous combination with 2 mg of oral E2 valerate. The effects on mammographic
      breast density, breast cell proliferation, and hormonal levels were followed for
      18 months. MAIN OUTCOME MEASURE(S): Change in mammographic breast density and
      breast cell proliferation. Correlations with levels of hormones, growth factors,
      and binding proteins. RESULT(S): Three women showed an apparent increase in
      density. For the remaining 17 women the changes were only a few percent.
      Digitized assessment of density showed strong correlations with visual
      classification scales (rs = 0.96-0.97). There was no increase in proliferation as
      expressed by the percentage of MIB-1-positive breast cells in fine-needle
      aspiration biopsies. Increase in breast density displayed a positive correlation
      with patients age (rs = 0.52) and an inverse relationship with levels of E2 (rs =
      -0.50) and free T (rs = -0.50). CONCLUSION(S): Low-dose intrauterine
      administration progestogen may develop into an attractive alternative for
      hormonal therapy in postmenopausal women as endometrial protection may be
      achieved at very low systemic levels.

PMID- 16580387
TI  - Pregnancy outcome in infertile patients with polycystic ovary syndrome who were
      treated with metformin.
AB  - OBJECTIVE: To analyze pregnancy complications and outcome in patients with
      polycystic ovary syndrome (PCOS) treated with metformin. DESIGN: Single center
      retrospective case analysis. SETTING: Private regional nonurban referral
      subspecialty practice. PATIENT(S): After 7 months of average metformin use, 188
      patients with PCOS (average infertility: 27 months) achieved 237 pregnancies.
      INTERVENTION(S): Of pregnancies established, metformin alone was used before
      conception in 124/237 (52%), oral fertility agents (CC or letrozole) in 81 (34%),
      gonadotropin therapy in 7 (3.0%), assisted reproduction in 17 (7.2%), and other
      fertility-promoting regimens in 8 (3.4%). MAIN OUTCOME MEASURE(S): Analysis of
      prepregnancy health parameters (weight, blood pressure, glucose tolerance,
      fasting and stimulated insulin levels) and pregnancy outcomes (miscarriage,
      pregnancy length, hypertension, gestational diabetes, weight gain, birth weight,
      sex ratio, congenital malformations, and breastfeeding success). RESULT(S):
      Metformin appears to decrease the rate of spontaneous abortion. The co
      morbidities of PCOS including obesity, insulin resistance, and glucose
      sensitivity served as indicators of increased risk for pregnancy complications,
      especially gestational diabetes. No increase in pregnancy-induced hypertension
      was evident. Prematurity was increased. Neither PCOS nor metformin use appears to
      increase the rate of congenital anomaly. PCOS did not affect lactation.
      CONCLUSION(S): PCOS or its co-morbidities are associated with poorer pregnancy
      outcome. Implications and interventions are discussed.

PMID- 16580386
TI  - Simvastatin improves biochemical parameters in women with polycystic ovary
      syndrome: results of a prospective, randomized trial.
AB  - OBJECTIVE: To test the hypothesis that statins improve hyperandrogenemia in women
      with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized trial.
      SETTING: Academic medical center. PATIENT(S): Forty-eight women with PCOS.
      INTERVENTION(S): Subjects were randomized to a statin group (simvastatin, 20 mg
      daily plus oral contraceptive pill [OCP]; n = 24) or an OCP group (OCP alone; n =
      24). MAIN OUTCOME MEASURE(S): Serum T. RESULT(S): Baseline parameters of both
      groups were comparable. After 12 weeks of treatment, serum T levels declined by
      41% in the statin group and by 14% in the OCP group. In the statin group, there
      was a greater decrease of LH (43% decrease vs. 9% in the OCP group) and a greater
      decline of LH/FSH ratio (44% vs. 12%). In the statin group, total cholesterol
      declined by 10% and low-density lipoprotein (LDL) by 24%. In the OCP group, total
      cholesterol increased by 8%, and LDL was unchanged. CONCLUSION(S): This is the
      first study demonstrating that statin decreases T levels and normalizes
      gonadotropin levels in women with PCOS. Statin therapy might offer a novel
      approach, providing endocrine and cardiovascular benefits.

PMID- 16580388
TI  - Hyperinsulinemia and circulating dehydroepiandrosterone sulfate in white and
      Mexican American women with polycystic ovary syndrome.
AB  - OBJECTIVE: To determine whether Mexican American women with polycystic ovary
      syndrome (PCOS), a population more insulin resistant than white women with PCOS,
      demonstrate differences in adrenal androgen production. DESIGN: Retrospective
      study. SETTING: University gynecology clinic and research laboratory. PATIENT(S):
      One hundred eleven white women and 50 Mexican American women with PCOS based on
      the 2003 Rotterdam Consensus Statement. INTERVENTION(S): Blood sampling, oral
      glucose tolerance testing, and ultrasonography. MAIN OUTCOME MEASURE(S): Serum
      total T, free T, DHEAS, and calculation of multiple insulin sensitivity indices
      after an oral glucose challenge. RESULT(S): Mexican American women with PCOS were
      significantly more insulin resistant than their white counterparts but had lower
      circulating levels of DHEAS, a reliable index of adrenal androgen production. Age
      and body mass index (BMI) were each inversely proportional to serum DHEAS, but no
      association was found between circulating insulin and serum DHEAS levels.
      Testosterone levels were similar between groups. CONCLUSION(S): The lower levels
      of DHEAS observed in the more insulin resistant Mexican American group with PCOS
      (compared to a similar group of white women living in the same locale) further
      corroborates the extent of phenotypic variability among specific PCOS
      populations. Hyperinsulinemia does not appear to significantly influence
      circulating adrenal androgen levels in PCOS.

PMID- 16580389
TI  - Evaluation of steroid receptors, coregulators, and molecules associated with
      uterine receptivity in secretory endometria from untreated women with polycystic
      ovary syndrome.
AB  - OBJECTIVE: To evaluate gene and protein expression of steroid receptors, nuclear
      receptor coregulators, and uterine receptivity markers in midsecretory phase
      endometria from untreated women with polycystic ovary syndrome (PCOS). DESIGN:
      Case-control study. SETTING: Hospital research unit. PATIENT(S): Eight patients
      with PCOS and eight fertile women of similar age to those with PCOS.
      INTERVENTION(S): Endometrial samples were obtained from women with PCOS (PCOSE)
      and normal (NE) women during the midsecretory phase of the menstrual cycle. MAIN
      OUTCOME MEASURE(S): Expression studies (immunohistochemistry, reverse
      transcription-polymerase chain reaction [RT-PCR] and Western blot). RESULT(S):
      Endometria from PCOS exhibit higher levels of messenger RNA (mRNA) and protein
      for estrogen receptor alpha and coactivators than NE. Epithelial cells had a
      greater expression of progesterone receptor in PCOSE, whereas, no differences
      were observed in gene and protein expression of the nuclear corepressor (NcoR)
      and the antiadhesion molecule mucin type-1 (MUC-1) between PCOSE and NE.
      Immunodetection for the coactivator ARA70 was higher in PCOSE than in NE; in
      contrast, expression of beta3-integrin in epithelia was lower in PCOSE than in
      control endometria. CONCLUSION(S): The higher response to steroid hormones of
      endometria from untreated PCOS-women induces diminished expression of beta3
      integrin, which partially explain implantation failure in PCOS patients.

PMID- 16580390
TI  - Gestrinone versus danazol as preoperative treatment for hysteroscopic surgery: a
      prospective, randomized evaluation.
AB  - OBJECTIVE: To compare danazol and gestrinone treatment as preoperative
      endometrial preparation for operative hysteroscopy. DESIGN: Prospective,
      randomized clinical study. SETTING: University department of gynecological,
      obstetrical sciences and reproductive medicine. PATIENT(S): One hundred thirty
      five patients with endouterine pathologies (endometrial polyps, submucous myoma,
      septate uterus). INTERVENTION(S): Patients pretreated with gestrinone (n = 68)
      and with danazol (n = 67) underwent operative hysteroscopy. MAIN OUTCOME
      MEASURE(S): Endometrial response to the medical pretreatment, side effects,
      procedure time, intraoperative bleeding, infusion volume, patient satisfaction.
      RESULT(S): Side effects were infrequent in both groups, though the patients'
      personal satisfaction was in favor of gestrinone. The rate of endometrial
      response was higher for the gestrinone group (97.1% vs. 83.6%). Operative time
      (mean +/- SD) was 12 +/- 1.8 and 15.2 +/- 1.9 minutes for the gestrinone and
      danazol groups, respectively. The gestrinone group showed a lower incidence of
      moderate bleeding (3% vs. 22.4%) and a lower infusion volume (2,100 +/- 200 mL
      vs. 2,400 +/- 250 mL). Regarding cervical dilatation time, no significant
      difference was found between the two groups (1.6 +/- 0.3 minutes vs. 1.5 +/- 0.4
      minutes). CONCLUSION(S): Both treatments are good ways to prepare the endometrium
      for operative hysteroscopy. However, the data suggest that gestrinone
      pretreatment is preferable to danazol.

PMID- 16580391
TI  - Influence of parity on first trimester endovascular trophoblast invasion.
AB  - OBJECTIVE: To assess the effect of parity on endovascular trophoblastic invasion
      in early pregnancy. DESIGN: Observational study. SETTING: Teaching hospital.
      PATIENT(S): Healthy women at 10-14 weeks of gestation. INTERVENTION(S): Surgical
      termination of pregnancy for nonmedical reasons. MAIN OUTCOME MEASURE(S):
      Products of conception were blindly examined histologically with regard to the
      extent of decidual endovascular trophoblast invasion. RESULT(S): Samples were
      obtained from 20 nulliparous and 10 parous women. The presence of normal
      intradecidual endovascular trophoblast invasion was identified with a similar
      frequency in both groups (P=.28). However, the proportion of decidual vessels
      with endovascular trophoblast invasion was significantly higher in parous women
      (60%) compared with nulliparous women (32%, P<.001). CONCLUSION(S): Endovascular
      trophoblast invasion in early pregnancy is more extensive in parous women who
      already had an uncomplicated pregnancy than in nulliparous women.

PMID- 16580392
TI  - Prolonged gonadotropin-releasing hormone agonist therapy reduced expression of
      nitric oxide synthase in the endometrium of women with endometriosis and
      infertility.
AB  - OBJECTIVE: To determine whether endometrial expression of endothelial nitric
      oxide synthase (eNOS) or inducible NOS (iNOS) protein in women with endometriosis
      associated infertility is different from that in the fertile controls, whether
      GnRH agonist (GnRH-a) regulates the endometrial expression of NOS in women with
      endometriosis-associated infertility, and whether there is a correlation between
      serum E2 or P levels, and the endometrial expression of eNOS or iNOS. DESIGN:
      Prospective controlled study. SETTING: University hospital for reproductive
      medicine and gynecologic endocrinology. PATIENT(S): Thirty patients with
      endometriosis-associated infertility and 19 patients with carcinoma in situ of
      the cervix. INTERVENTION(S): Endometrial biopsy specimens and blood samples. MAIN
      OUTCOME MEASURE(S): Endometrial eNOS and iNOS protein relative levels and serum
      concentrations of E2 or P. RESULT(S): By Western blot analysis, iNOS was not
      detected, and a unique menstrual cycle-dependent expression of eNOS was observed.
      Eutopic endometrium in women with endometriosis-associated infertility before
      GnRH-a treatment showed higher levels of eNOS than that of the control group.
      After 3 months of GnRH-a therapy, eNOS levels in the endometrium were reduced. In
      addition, a significant positive correlation was found between serum E2 or P
      concentrations, and the endometrial expression of eNOS. CONCLUSION(S): The GnRH-a
      treatment attenuated the endometrial expression of eNOS in women with
      endometriosis-associated infertility. Endogenous ovarian steroids influence
      endometrial eNOS expression.

PMID- 16580393
TI  - Letrozole vs. clomiphene citrate in patients with ovulatory infertility.
AB  - OBJECTIVE: To compare the effectiveness of letrozole and clomiphene citrate (CC)
      in ovulatory patients with borderline male factor infertility, early stage
      endometriosis, and unexplained infertility. DESIGN: Prospective quasi-randomized
      trial. SETTING: University infertility clinic. PATIENT(S): Forty-six consecutive
      patients with ovulatory infertility were recruited. Twenty-five patients (67
      cycles) were given CC and 21 patients (52 cycles) were given letrozole. Both
      drugs were given orally on days 3-7 of menses. INTERVENTION(S): Letrozole, CC,
      ovulation induction, IUI, timed intercourse. MAIN OUTCOME MEASURE(S): Number of
      follicles, endometrial thickness, and pregnancy rates. RESULT(S): The median
      serum E2 concentration on the day of hCG administration in the letrozole and CC
      groups were 191.5 pmol/L and 476.0 pmol/L, respectively. The median endometrial
      thickness on the day of hCG were 8 mm in both groups. Ovulation occurred in 81%
      (42/52) of the letrozole-treated and 85% (57/67) of the CC-treated patients.
      Pregnancy rate (PR) per cycle was 9% (5/52) in the letrozole group and 12% (8/67)
      in the CC group. CONCLUSION(S): Letrozole and CC have comparable effectiveness in
      ovulatory patients with borderline male factor infertility, early stage
      endometriosis, and unexplained infertility.

PMID- 16580394
TI  - Increased luteinizing hormone pulse frequency in obese oligomenorrheic girls with
      no evidence of hyperandrogenism.
AB  - OBJECTIVE: To determine whether obese, nonhirsute adolescents with oligomenorrhea
      exhibit similar increased LH pulse secretion patterns compared with obese girls
      with polycystic ovary syndrome (PCOS). DESIGN: Prospective, observational study.
      SETTING: Tertiary university hospital. PATIENT(S): Nine obese girls with
      oligomenorrhea, 15 with PCOS, and 10 controls. INTERVENTION(S): Twenty-four-hour
      IV blood sampling for LH (every 10 minutes); measurement of steroid hormones
      (every 12 hours); and injection of leuprolide acetate (10 microgm/kg SC). MAIN
      OUTCOME MEASURE(S): Twenty-four-hour, wake, and sleep LH mean serum
      concentration, pulse frequency, amplitude; steroid hormones, including free
      androgen index (FAI); and pre- and post-leuprolide acetate 17-hydroxyprogesterone
      measurements. RESULT(S): Twenty-four-hour LH pulse frequency in oligomenorrheic
      girls (18.6 +/- 1.2) (mean +/- SE) was comparable to that in girls with PCOS
      (20.9 +/- 0.7) and greater than in normal girls (13.4 +/- 0.8). The pulse number
      during both sleep and wake was identical in oligomenorrheic and PCOS girls and
      significantly greater than that of normal girls. Mean 24-hour LH level, serum
      androgen levels, and FAI in oligomenorrheic girls were equivalent to those of
      normal controls and lower than those of PCOS girls. CONCLUSION(S): These
      preliminary results indicate that obese girls with oligomenorrhea exhibit
      increased LH pulse frequency in the absence of clinical and/or biochemical
      evidence of hyperandrogenism.

PMID- 16580395
TI  - Rapidly growing adenomyosis during the first trimester: magnetic resonance
      images.
AB  - We report an unusual case in which a rapidly growing adenomyosis was identified
      during the first trimester in a 35-year-old infertile woman achieving pregnancy
      after controlled ovarian hyperstimulation. Relevant images are shown by magnetic
      resonance imaging.

PMID- 16580397
TI  - Aneuploidy screening in a coelomic sample from a missed abortion using sequential
      fluorescence in situ hybridization.
AB  - OBJECTIVE: To investigate the incidence of aneuploidy by using sequential
      interphase fluorescence in situ hybridization (FISH) in an uncultured coelomic
      fluid sample from a missed abortion. DESIGN: Case report. SETTING: Fetal medicine
      and gynecology departments of two university hospitals. PATIENT(S): A 33-year-old
      woman with a missed abortion. INTERVENTION(S): Molecular cytogenetic analysis was
      performed on coelomic fluid cells and placental tissue by applying a multicolor
      probe for chromosomes 13, 16, 18, 21, and 22 in a first layer of hybridization,
      followed by a triple-color probe for chromosomes X, Y, and 18. MAIN OUTCOME
      MEASURE(S): Analysis of limited number of coelomic cells by using sequential
      FISH. RESULT(S): The results showed trisomy 13 in 92% of nuclei. Diploid cells
      were observed at low levels (4%), but these were caused by maternal cell
      contamination, as revealed after reprobing with the X,Y,18 triple-color probe
      set. The result also was confirmed in the placental tissue. CONCLUSION(S): We
      conclude that sequential FISH analysis can overcome problems associated with
      limited cell numbers, accurately detect aneuploidy, and distinguish between
      maternal cell contamination and genuine mosaicism in coelomic cells and placental
      tissue from missed abortions. It also has the potential to be applied for rapid
      aneuploidy screening in clinical cases after coelocentesis and to be used for
      follow-up analysis of pregnancies established after preimplantation genetic
      screening.

PMID- 16580396
TI  - Addison's disease presenting as male infertility.
AB  - OBJECTIVE: To present a case of primary male infertility with severe oligospermia
      and hyperpigmented skin as the main presenting clinical signs. DESIGN: Case
      report. SETTING: University-affiliated teaching hospital. PATIENT(S): A 32-year
      old male with severe oligospermia and his 31-year-old female partner with normal
      cycles. INTERVENTION(S): Hydrocortisone, fludrocortisone, methimazole, and
      eventual IVF. MAIN OUTCOME MEASURE(S): Improved semen analysis, correction of
      Addison's disease, correction of hyperthyroidism, and ART pregnancy. RESULT(S):
      Severe oligospermia of 5 million per milliliter with 15% motility and ACTH level
      of 2,800 pg/mL on presentation. Endocrinology evaluation revealed cortisol of
      <0.1 microg/dL, and Cortrosyn test showed no response (Addison's disease). The
      patient was incidentally found to have a thyroid stimulating hormone level of
      <0.1 microIU/mL, T4 of 9.5 microg/dL, Free T4 Index calculation of 11.6
      microg/dL, and quantitative triiodothyronine of 273 ng/dL on presentation. His
      Addison's disease was managed with hydrocortisone and fludrocortisone, and his
      hyperthyroidism, with methimazole. Semen parameters increased to 34 million per
      milliliter with 45% motility and 5% Kruger morphology 1 year after initial
      presentation. Hormone parameters normalized. Rather than allowing for more time
      for natural conception or IUI, the couple decided to proceed with IVF because of
      insurance coverage before semen parameters normalized. CONCLUSION(S): This is the
      first reported case of Addison's disease presenting as male infertility with
      hyperpigmentation of the skin being the only other presenting sign. The
      underlying etiology of the Addison's in this case remains uncertain, but it is
      presumed because of autoimmunity. Addison's disease may be associated with
      hyperthyroidism, and hyperthyroidism may have contributed to the oligospermia.
      This case highlights why men with abnormal semen parameters should be thoroughly
      evaluated before proceeding with assisted reproduction.

PMID- 16580398
TI  - Characterization of a de novo balanced 1;Y translocation in a phenotypically
      normal twin male infant.
AB  - OBJECTIVE: To report a translocation between an autosome and the Y chromosome.
      DESIGN: Amniocentesis of a fetus because of mother's advanced age followed by
      karyotype and PCR analysis. SETTING: Tertiary health center. PATIENT(S): A
      phenotypically normal twin male infant. INTERVENTION(S): Karyotype with G and Q
      banding and amplification of testis-specific protein 1-Y and of azoospermia
      factor (AZF) a, AZFb, AZFc, and distal AZFc regions of Y chromosome. MAIN OUTCOME
      MEASURE(S): Karyotype, PCR. RESULT(S): We report a phenotypically normal twin
      male infant with de novo 46,ChiY,t(1;Y)(p22;p11) that was found in amniocentesis.
      In genetic counseling, it was recommended that the fetus be monitored through a
      detailed prenatal ultrasonographic examination, which did not indicate any
      pathological findings. A phenotypically normal male baby was born who is now a 12
      month-old healthy infant. The karyotype was confirmed in the peripheral blood
      with G and Q banding. Amplification of testis-specific protein 1-Y, AZFa, AZFb,
      AZFc, and distal AZFc regions of the Y chromosome did not reveal any deletions.
      CONCLUSION(S): We cannot predict whether this male infant will have oligospermia
      or azoospermia as an adult and, furthermore, whether in case of fertility there
      is a risk for unbalanced autosome;Y translocations in the offspring, with
      congenital malformations and dysmorphic features. This case illustrates the
      complexities in counseling for prenatally diagnosed de novo autosome;Y
      translocations and the need for additional cases to be reported.

PMID- 16580399
TI  - Pure XY gonadal dysgenesis and agenesis in monozygotic twins.
AB  - OBJECTIVE: To report a case of monozygotic twin sisters who had discordant
      gonadal dysgenesis although each had a normal 46,XY karyotype. DESIGN: Case
      report. SETTING: University tertiary hospital. PATIENT(S): Seventeen-year-old
      twin sisters, one with gonadal agenesis and the other with pure gonadal
      dysgenesis followed by dysgerminoma. INTERVENTION(S): Blood samples were obtained
      for karyotyping and short tandem repeat polymorphism analysis (10 markers). Both
      patients underwent gonadectomy. MAIN OUTCOME MEASURE(S): Both sisters are well at
      time of report after gonadectomy for the sister with dysgerminoma and diagnostic
      laparoscope for the other. RESULT(S): Dysgerminoma and atrophic ovarian stromal
      and tubal structures. CONCLUSION(S): Monozygotic twins can have discordant
      gonadal dysgenesis even though they are identical genetically.

PMID- 16580400
TI  - Bowel endometriosis and schistosomiasis: a rare but possible association.
AB  - OBJECTIVE: To report the case of a patient submitted to laparoscopic bowel
      resection in whom histology revealed endometriosis and schistosomiasis. DESIGN:
      Case report. SETTING: Multidisciplinary group practice and teaching hospital.
      PATIENT(S): A 31-year-old patient with pelvic pain. INTERVENTION(S): Laparoscopic
      bowel resection. MAIN OUTCOME MEASURE(S): Laparoscopic treatment of endometriosis
      affecting the sigmoid. RESULT(S): Histology performed on tissue removed at
      surgery revealed epithelioid granulomas with birefringent and partially calcified
      eggs characteristic of Schistosoma mansoni within an endometriotic lesion
      affecting the entire width of the sigmoid. CONCLUSION(S): Endometriosis and
      schistosomiasis may be present simultaneously in patients with bowel symptoms and
      pelvic pain.

PMID- 16580401
TI  - Preliminary study of the relationship between DAZ gene copy deletions and
      spermatogenic impairment in Chinese men.
AB  - Copy deletion screening of DAZ gene family on the Y chromosome in 485 patients
      with idiopathic azoospermia or oligozoospermia and 236 fertile men revealed that
      the prevalence of deletion patterns of the entire DAZ gene and DAZ1/DAZ2 gene
      were significantly higher in the patients than in fertile men. The deletion
      patterns correlate with spermatogenic impairment in a Chinese population.

PMID- 16580402
TI  - Effect of gonadotropin-releasing hormone agonist and antagonist on proliferation
      and apoptosis of human luteinized granulosa cells.
AB  - The GnRH agonist leuprolide acetate (LA) inhibited DNA synthesis in epidermal
      growth factor-stimulated human granulosa luteinized cell cultures. This effect
      was blocked by the prior addition of a GnRH antagonist antide (ANT), and this
      compound per se was able to produce a stimulatory effect of DNA synthesis on
      basal conditions. Leuprolide acetate produced an increase in the percentage of
      apoptotic cells, and when these two factors were co-incubated, ANT blocked the
      apoptotic effect produced by LA.

PMID- 16580403
TI  - Prompt diagnosis of ectopic pregnancy with the human chorionic gonadotropin test
      using exuded extract from endometrial curettings.
AB  - Using saline solution including exuded extract from uterine curettings, hCG tests
      were performed in 63 women in whom there was a suspicion of ectopic pregnancy,
      and their results correlated highly with the microscopic existence of chorionic
      villi and trophoblasts. Ectopic pregnancy can be mostly excluded when the test is
      positive, and either ectopic pregnancy or complete abortion is probable when it
      is negative.

PMID- 16580404
TI  - "Recurrent abortion and live birth rate per patient".

PMID- 16580405
TI  - Recurrent abortion and live birth rate per patient.

PMID- 16580406
TI  - A challenge for scientific medical journals: quest for the holy p-pub/e-pub
      balance.

PMID- 16580409
TI  - Comparability of the standing and supine standard electrocardiograms and standing
      sitting and supine stress electrocardiograms.
AB  - The aim of this study was to evaluate whether change in the patients' position
      during the electrocardiogram (ECG) recording alters the various components of the
      ECG curve. Concerns whether ECGs in medically compromised patients recorded in a
      sitting position should be considered "standard" tracings and whether ECGs
      recorded in the supine and standing positions and ECGs recorded in different
      positions in the Exercise Laboratory are interchangeable provided the impetus for
      this study. The ECG was recorded in the supine and standing positions in 10
      patients using standard electrode placement and in the sitting, standing, and
      supine positions in 16 patients using the Mason-Likar electrode system.
      Comparisons of sums of P waves and QRS complexes of various combinations of ECG
      leads from recordings in different positions and amplitudes of Q, R, and S waves
      of all 12 ECG leads revealed stability in the standard and stress ECGs, although
      few statistically significant but minor changes were noted in some comparisons,
      which, however, could not be expected to have any diagnostic significance.
      Comparison of standard ECGs recorded in patients in the supine and standing
      positions and stress ECGs recorded in the sitting, standing, and supine positions
      are interchangeable; this should allay concerns about recording the standard ECG
      in unconventional positions and may facilitate and make more cost-effective ECG
      recording in busy outpatient clinic environments.

PMID- 16580408
TI  - The failure of years of experience with electrocardiographic transmission from
      paramedics to the hospital emergency department to reduce the delay from door to
      primary coronary intervention below the 90-minute threshold during acute
      myocardial infarction.
AB  - INTRODUCTION: Emergency medical services (EMS), hospital emergency departments,
      and cardiologists have taken steps to reduce time to reperfusion therapy by
      implementation of aggressive acute myocardial infarction treatment and triage
      protocols. Data indicate that significant myocardial salvage requires reperfusion
      within 2 hours, and the current American College of Cardiology guideline is 90
      minutes after hospital emergency department admission. MATERIALS AND METHODS: To
      minimize delays in time to reperfusion in an urban-rural North Carolina County,
      Guilford County EMS and the Moses Cone Hospital have collaborated to implement
      transmission of EMS electrocardiographs (ECGs) to the emergency department. The
      study population included 92 patients who were transported by EMS and received
      primary coronary intervention during the second, third, and fourth years after
      initiation of this intervention in 1993. RESULTS: The median time from symptom
      onset to the initial ECG was 77 minutes. There was an additional 23 minutes
      between the availability of this ECG and the arrival of the patient at the
      emergency department. In the first year of the intervention, the time from
      hospital arrival to percutaneous coronary intervention was 80 minutes. In years 2
      through 4, they were 93, 85, and 94 minutes, respectively. In 2003, 10 years
      after the intervention, the time from hospital arrival to percutaneous coronary
      intervention was 113 minutes. CONCLUSION: Initial gains in the time from hospital
      arrival to percutaneous coronary intervention, attributed to acquisition of the
      ECG in the prehospital setting, were not sustained over 10 years.

PMID- 16580410
TI  - Does the abnormal signal-averaged electrocardiogram predict future appropriate
      therapy in patients with implantable cardioverter-defibrillators?
AB  - BACKGROUND: Several studies have documented the prognostic significance of the
      signal-averaged electrocardiogram (SAECG) both after myocardial infarction and
      nonischemic cardiomyopathy. However, whether the SAECG can identify patients with
      implantable cardioverter-defibrillator (ICD) who receive appropriate therapy has
      not been hitherto completely investigated. METHODS: Between August 2002 and
      August 2004, 83 consecutive ICD patients who had had SAECGs recorded were
      enrolled in this study. All patients were followed up in the outpatient ICD
      clinic, and interrogated electrograms were collected. RESULTS: Over 9.0 +/- 2.8
      months of follow-up, 27 (32%) patients had appropriate ICD therapy for
      ventricular tachycardia or fibrillation; 15 (55.6%) patients had abnormal; and
      the remaining 12 (44.4%) had normal SAECGs. Of the 56 patients with no
      appropriate therapy, 27 (48.2%) and 29 (51.8%) patients had abnormal and normal
      SAECGs, respectively. There were no statistically significant differences between
      the 2 groups in SAECG findings (P = .41). A Cox regression analysis showed that
      the left ventricular ejection fraction was the only predictor of appropriate
      therapy (P = .02). Subgroup analysis of the patients with coronary artery disease
      and spontaneous monomorphic ventricular tachycardia indicated that left
      ventricular ejection fraction (P = .03) and abnormal SAECG (P = .02) were
      predictors of appropriate therapy. CONCLUSIONS: Our data demonstrate that except
      for the subgroup of patients with coronary artery disease presenting with
      monomorphic ventricular tachycardia, the SAECG did not predict ventricular
      tachyarrhythmia recurrence and, hence, appropriate ICD therapy. Thus, SAECG
      findings should generally not be a factor in decision for ICD implantation.

PMID- 16580411
TI  - Difficulties in assessing the presence, duration, severity, extent, and evolution
      of acute myocardial ischemia and infarction: ischemic ST-segment counterpoise as
      a plausible explanation.

PMID- 16580412
TI  - ST segment deviation counterpoise--a different perspective.

PMID- 16580414
TI  - Vectorcardiographic ST deviations related to increased heart rate in the absence
      of ischemia in an experimental pig model.
AB  - The electrocardiographic ST segment may change when heart rate (HR) increases. We
      aimed to analyze vectorcardiographic ST relation and myocardial conditions during
      controlled HR increases in anesthetized pigs. The relative parameters ST change
      vector magnitude and ST change vector angle were calculated at paced HRs ranging
      from 85 to 175 beats per minute. ST change vector magnitude increased from
      baseline 6.3 +/- 1.3 to 26.0 +/- 3.1 microV (P < .01; range, 4-50 microV) at HR
      175 beats per minute with similar changes in ST change vector angle, whereas the
      absolute parameter ST vector magnitude demonstrated a heterogeneous pattern
      without any systematic relation to HR changes. Microdialysis results from left
      ventricular wall, with analysis of glucose, lactate, and pyruvate, showed no sign
      of ischemia during pacing. Potassium concentrations did not change during pacing.
      We conclude that significant HR-related ST vector changes can occur in the
      absence of myocardial ischemia.

PMID- 16580413
TI  - Development of an automated Selvester Scoring System for estimating the size of
      myocardial infarction from the electrocardiogram.
AB  - Although the Selvester Scoring System for estimating the size of myocardial
      infarction from the standard 12-lead electrocardiogram (ECG) has potential
      clinical value, it has found limited application because of the difficulties in
      making precise and reproducible measurements. The objective of this study was to
      develop software to automate the Selvester Scoring System, thus allowing wider
      application of the technique. The study was carried out using a training set
      consisting of ECG data recorded from 705 individuals with and without previous
      myocardial infarction. Algorithms for the 50 criteria in the Selvester Scoring
      System were iteratively improved by comparison of scores obtained by 2
      experienced cardiologist investigators with those generated by the program. The
      final version was evaluated in a test set consisting of 60 ECGs by comparing
      scores derived by cardiologist investigator with those obtained by the program.
      The disagreements occurred only in 1.1% of the score comparisons and in 1.6% of
      the specific measurements. In all cases in which a disagreement occurred, it
      resulted from very small differences in measurements. These results indicate that
      the algorithm for automated application of the Selvester Scoring System is
      adequate for both clinical and research applications.

PMID- 16580415
TI  - Progression of partial to advanced interatrial block.
AB  - Interatrial block (IAB), prolonged conduction between the atria, is denoted by P
      waves of 110 milliseconds or more and may manifest as partial or advanced.
      Theoretically, partial IAB may progress to its advanced counterpart if conduction
      delay increases to complete block. However, there have been no reports of such
      progression, and electrophysiologic studies have not shown this phenomenon. We
      briefly review the interatrial conducting pathways of IAB and present the first
      documentation of possible progression of partial to advanced IAB.

PMID- 16580416
TI  - Right ventricular enlargement mimicking electrocardiographic left ventricular
      pacing.
AB  - Electrocardiographic right bundle branch block morphology during cardiac pacing
      is occasionally the result of accidental placement of pacemaker or defibrillator
      leads into the left ventricle. Inadvertent lead placement in the left heart is
      associated with a risk of systemic embolism. Previous authors have attempted to
      define safe (right ventricular origin) and unsafe (left ventricular origin)
      patterns of right bundle branch block during pacing. We report a case of a
      patient with severe dilated cardiomyopathy and a correctly positioned pacemaker
      defibrillator lead in the right ventricular apex, who meets electrocardiographic
      criteria for lead implantation into the left ventricle.

PMID- 16580417
TI  - Vagal nerve-mediated vasospasm-induced lethal ventricular fibrillation.
AB  - We report a case of variant angina complicated by lethal ventricular
      fibrillation. Serial ambulatory electrocardiogram monitoring revealed high
      frequency spectra reflecting augmented vagal nerve activity preceding the
      vasospastic episodes. Our case suggests that heart rate variability analysis can
      help identify potential unexpected sudden cardiac death in patients with variant
      angina.

PMID- 16580418
TI  - Experience with an ambulatory 12-lead Holter recording system for evaluation of
      pediatric dysrhythmias.
AB  - BACKGROUND: The 12-lead electrocardiogram demonstrates noninvasively many details
      concerning cardiac arrhythmias and their mechanism, but only for a limited
      period. A Holter system can record heart rhythm for a longer period, but shows 2
      or 3 leads only. An ambulatory 12-lead Holter recording system combines the
      advantages of both. We report on our experience with the 12-lead Holter system in
      children. STUDY POPULATION: Twenty-four patients (age range, 3-22 years)
      underwent one or more 12-lead Holter recordings. Twelve patients had suspected or
      documented tachyarrhythmia, and 12 patients had suspected or proven long QT
      syndrome (LQTS). RESULTS: In the tachyarrhythmia group, 4 patients had
      supraventricular tachycardia and 7 ventricular tachycardia (VT). In the
      supraventricular tachycardia, group 1 patient had intra-atrial reentrant
      tachycardia with a single reentrant circuit, whereas another had multiple P-wave
      morphologies, suggesting multiple circuits. Two others had evidence for concealed
      atrioventricular accessory pathways. One patient had isolated supraventricular
      ectopy. In the VT group, 4 patients had uniform VT, and 3 patients had
      polymorphic VT. One patient with LQTS had macroscopic T-wave alternans. Two
      others showed intermittent extreme QT prolongation and T-wave notching during 12
      lead Holter recording. THERAPEUTIC IMPLICATIONS: Patients with uniform VT
      underwent catheter ablation, guided in 2 instances by intracardiac pace mapping
      and comparison with the 12-lead Holter QRS morphology. All reentrant
      supraventricular arrhythmias with single P-wave morphology were ablated. One
      patient with intra-atrial reentrant tachycardia and multiple circuits received an
      antitachycardia pacemaker. In the LQTS group, the neonate with T-wave alternans
      received mexiletine in addition to beta-blocker therapy. CONCLUSION: In
      individual patients, the 12-lead Holter system provides important additional
      information about the arrhythmia and helps to plan appropriate therapy.
      Intermittent T-wave morphology changes can be diagnosed using 12-lead Holter
      recordings in patients with LQTS, allowing dynamic T-wave changes to be
      monitored. In specific cases, this may help identify patients with LQTS and also
      influence pharmacological therapy.

PMID- 16580419
TI  - Effects of coronary revascularization and concomitant aneurysmectomy on QT
      interval duration and dispersion.
AB  - A reduction in QT dispersion (QTd) has been previously shown in patients
      receiving thrombolytics and undergoing coronary artery bypass grafting (CABG).
      The purpose of the present study was to investigate changes occurring in
      corrected QT intervals or QT dispersion after CABG and concomitant aneurysmectomy
      in the same session. The study population included 43 patients with coronary
      artery disease with left ventricular aneurysm (LVA). The control group included
      32 patients with coronary artery disease without LVA. The study patients
      underwent CABG and aneurysmectomy in the same surgical session. Corrected maximum
      and minimum QT interval duration (QTcmax and QTcmin) and corrected QT dispersion
      (QTcd) were measured in the study patients before and after surgery. QTcmax and
      QTcd in the patients with LVA were significantly higher than in the patients
      without LVA (P < .001 and P < .001, respectively). QTcmax and QTcd in the
      patients with LVA were significantly shortened after surgery (P < .001 and P <
      .001, respectively). This study showed that QTcmax and QTcd values are
      significantly reduced after CABG and concomitant aneurysmectomy. We have
      suggested that coronary revascularization and left ventricular reconstruction in
      the same session have beneficial effects on QT interval duration and dispersion.

PMID- 16580420
TI  - Importance of hepatitis C coinfection in the development of QT prolongation in
      HIV-infected patients.
AB  - BACKGROUND: Case reports and unblinded studies suggest that human
      immunodeficiency virus (HIV) disease is associated with QT prolongation and
      torsade de pointes ventricular tachycardia. Hepatitis C coinfection is common in
      patients with HIV disease, and cirrhosis is also associated with QT prolongation.
      We therefore undertook a systematic analysis of the role of liver injury,
      nutritional state, and coinfection with hepatitis C in the etiology of QT
      prolongation in HIV disease. METHODS: We performed a blinded, controlled
      retrospective cohort study of 1648 patients over a 3-year period at a university
      affiliated municipal hospital. All electrocardiograms were included if patients
      with HIV disease had measurements of CD4 count and viral load within 3 months and
      serum electrolytes within 30 days (n = 816). Control subjects were chosen
      randomly from the general medicine service (n = 832). QT interval was measured in
      lead II and corrected for heart rate by Bazett's formula (QTc). RESULTS: QTc was
      slightly but significantly longer in patients with HIV disease than in controls
      (443 +/- 37 vs 436 +/- 36 milliseconds, P < .001). Patients with hepatitis C had
      more pronounced QTc prolongation (452 +/- 41 vs 437 +/- 35 milliseconds, P <
      .001). CD4 count, HIV viral load, and HIV medications had no effect on QTc. When
      patients with hepatitis C were excluded from the analysis, there was no
      statistical difference between patients with HIV disease and controls (438 +/- 34
      vs 436 +/- 36 milliseconds, P = .336). Multiple linear regression revealed that
      both HIV and hepatitis C infection predicted QTc prolongation, as did age, female
      sex, history of hypertension, use of opiates, low serum K+ and albumin, and high
      AST. Hepatitis C coinfection nearly doubled the risk of QTc of 470 milliseconds
      or greater in patients with HIV disease (29.6% vs 15.8%, P < .001). CONCLUSIONS:
      Human immunodeficiency virus and hepatitis C infections both independently
      prolong QTc. Coinfection with hepatitis C greatly increases the likelihood of
      clinically significant QTc prolongation in patients with HIV disease.

PMID- 16580421
TI  - Heart rate-corrected QT interval duration is significantly associated with blood
      pressure in Chinese hypertensives.
AB  - INTRODUCTION: Many studies demonstrated that a prolonged heart rate-corrected QT
      interval (QTc) increases the risk of malignant ventricular arrhythmias and sudden
      death. METHODS: We measured the electrocardiogram and blood pressure of 1480
      hypertensive patients and assessed the relationship between the length of QTc and
      blood pressure. RESULTS: The mean QTc is longer in female than in male
      participants. There was a positive association between QTc and blood pressure in
      both men and women. The estimated increase in systolic and diastolic blood
      pressure for each 100-millisecond increase in QTc was 6.4 and 5.0 mm Hg in men
      and 3.7 and 2.5 mm Hg in women, respectively. CONCLUSION: Our study demonstrated
      a significant positive relationship between the QTc interval and baseline blood
      pressure in a Chinese hypertensive population.

PMID- 16580422
TI  - The effects of trimetazidine on heart rate variability in patients with slow
      coronary artery flow.
AB  - OBJECTIVE: We sought to examine the effect of trimetazidine (TMZ) on heart rate
      variability (HRV), endothelin-1 (ET-1), NO, and anginal symptoms in patients with
      slow coronary artery flow (SCAF). METHODS: The 48 patients with SCAF (29 women
      and 19 men; mean age, 52 +/- 9 years) were included in the study. Twenty
      milligrams TMZ 3 times a day or matched placebo were given randomly in a double
      blinded fashion for 4 weeks. Patients were divided into 4 groups as follows:
      exercise-positive, TMZ-given group (group A, n = 12); exercise-positive, placebo
      given group (group B, n = 12); exercise-negative, TMZ-given group (group C, n =
      12); and exercise-negative, placebo-given group (group D, n = 12). RESULTS: After
      TMZ treatment, HRV parameters, including SD of the all R-R intervals, SD of the
      averages of R-R intervals in all 5-minute segments of the entire recording,
      percentage of R-R intervals with more than 50-millisecond variation, and the
      square root of the mean of the sum of the squares of differences between adjacent
      R-R intervals, significantly improved both in exercise-positive and exercise
      negative groups when compared with baseline. After TMZ treatment, ET-1 and NO
      levels significantly altered both in exercise-positive and exercise-negative
      groups when compared with baseline (17.7 +/- 2.7 vs 13.9 +/- 2.8 pg/mL [P = .01]
      and 18.1 +/- 3.8 vs 14.2 +/- 2.6 pg/mL [P = .01], respectively). After TMZ
      treatment, NO levels significantly increased in both exercise-positive and
      exercise-negative groups when compared with baseline (36.4 +/- 5.4 vs 43.3 +/-
      6.8 micromol/L [P = .01] and 36.8 +/- 7.8 vs 43.3 +/- 4.8 micromol/L [P = .01],
      respectively). However, in placebo group, neither HRV parameters nor ET-1 and NO
      levels altered when compared with baseline. Also, after treatment, a significant
      correlation was detected between HRV parameters, including SD of the averages of
      R-R intervals in all 5-minute segments of the entire recording, SD of the all R-R
      intervals, percentage of R-R intervals with more than 50-millisecond variation,
      and the square root of the mean of the sum of the squares of differences between
      adjacent R-R intervals, and NO and ET-1 levels in TMZ group but not placebo.
      CONCLUSION: Short-term TMZ therapy improved HRV parameters and endothelial
      products such as ET-1 and NO as well as anginal symptom in patients with SCAF.
      Improvement in HRV parameters was correlated with ET-1 and NO levels.

PMID- 16580423
TI  - Ventricular tachycardia late after repair of congenital heart disease: efficacy
      of combination therapy with radiofrequency catheter ablation and class III
      antiarrhythmic agents and long-term outcome.
AB  - OBJECTIVE: This study investigated the treatment of ventricular tachycardia (VT)
      after repair of tetralogy of Fallot or double outlet of the right ventricle.
      BACKGROUND: The ideal antiarrhythmic therapy for VT in patients after repair of
      congenital heart disease, especially without left ventricular dysfunction, has
      not yet been established. METHODS: Seven consecutive patients (2 women and 5 men)
      with stable monomorphic sustained VT were investigated. The mean age was 25 +/- 7
      years (range, 16-35 years). Four patients had undergone surgical repair of
      tetralogy of Fallot, and 3 had surgical correction of double outlet of the right
      ventricle at the mean age of 18 +/- 7 years (range, 9-27 years) before
      documentation of the arrhythmia. RESULTS: The mean ejection fraction of the left
      ventricle was 60% +/- 8% (range, 50-72). Fourteen sustained monomorphic VTs were
      induced in 7 patients using programmed electrical stimulation. The mean cycle
      length of tachycardia was 346 +/- 77 milliseconds (range, 260-480 seconds). The
      site of the surgical correction of the right ventricle was associated with the
      origin of VT in all patients. Radiofrequency catheter ablation was attempted in 8
      VTs in 7 patients: 7 clinical and 1 nonclinical VTs. In 6 patients, class III
      antarrhythmic agents were added because VT remained inducible after ablation.
      During a follow-up of 61 +/- 29 months (range, 15-110 months), there were no
      recurrences of VT. CONCLUSION: In patients with drug-refractory VT originating
      from the right ventricle late after congenital heart disease, and when their left
      ventricular function do not deteriorate, combined therapy for radiofrequency
      catheter ablation with class III antiarrhythmic agents might effective and should
      be considered as a therapeutic option.

PMID- 16580424
TI  - P-wave morphology correlation with left atrial volumes assessed by 2-dimensional
      echocardiography.
AB  - To correlate prespecified P-wave morphologies with echocardiographically derived
      left atrial volumes (LAVs), we studied a convenience sample of 71 patients with
      predominantly normal left ventricular systolic function (mean ejection fraction =
      58.2% +/- 6.6%) who underwent concurrent 2-dimensional echocardiogram and 12-lead
      electrocardiogram. Left atrial volume was calculated from apical end-systolic
      images by the biplane method of disks and was indexed for body surface area
      (BSA). Electrocardiograms were assessed manually with calipers, measuring leading
      edge to leading edge. Patients included 34 men and 37 women with a mean age of 53
      +/- 14 years. P-wave duration/PR-segment duration in lead II and depth and
      duration of terminal P wave in lead V1 (P terminal force) correlate poorly with
      LAV and provided only modest predictive power (area under receiver operating
      characteristic curve = 0.466-0.619 and r = 0.30-0.42, P = .014-.021). Total P
      wave duration in lead II correlated moderately (r = 0.47, P < .001) and predicted
      LAV (LAV/BSA = 8.0 + 0.2 [P-wave duration in lead II]), as did P-wave area in
      lead II (r = 0.49, P < .001) (LAV/BSA = 18.6 + 1.7 [P-wave duration in lead II]).
      The 4 P-wave morphologies were found to be poorly sensitive but highly specific
      for left atrial enlargement.

PMID- 16580425
TI  - Detecting left atrial enlargement by ECG--a comparison of 4 methods.

PMID- 16580426
TI  - The prevalence of cardiac ectopy in elderly patients with echocardiographically
      normal hearts is not increased by significant coronary artery disease.
AB  - ISSUE: A higher frequency of abnormal heart rhythms has previously been shown in
      elderly subjects with overtly normal hearts as demonstrated by noninvasive
      testing. However, no prior study on elderly patients with echocardiographically
      structurally normal hearts has distinguished cardiac dysrhythmia incidence based
      on the presence or absence of angiographically documented coronary artery disease
      (CAD). METHODS: We performed 24-hour ambulatory monitoring on patients with no
      coronary stenosis of greater than 30% and normal left ventricular (LV) systolic
      function by angiography. This group was then compared with a group of elderly
      patients with normal LV systolic function and at least one major coronary artery
      stenosis of 70% or greater. All patients had echocardiographically normal LV wall
      thickness and systolic function and no significant valvular disease. RESULTS: The
      experimental group was composed of 15 patients with CAD aged 71 +/- 6 years. The
      control group without significant CAD was composed of 20 patients aged 73 +/- 4
      years (P = not significant [NS]). There was no difference with respect to
      prevalence of hypertension, use of calcium-channel blockers, and history of
      smoking. There was no difference between the groups with regard to the number of
      premature atrial contractions (467 +/- 759 [experimental] vs 672 +/- 1789
      [control]; P = NS); premature ventricular contractions (359 +/- 599
      [experimental] vs 290 +/- 858 [control]; P = NS); and prevalence of ventricular
      couplets, ventricular tachycardia, paroxysmal atrial fibrillation, and
      supraventricular tachycardia (all P = NS). CONCLUSIONS: These findings indicate
      that the prevalence of cardiac dysrhythmias in elderly patients with
      echocardiographically normal hearts is not influenced by the presence of
      angiographically significant CAD.

PMID- 16580427
TI  - Conducting an economic analysis to assess the electrocardiogram's value.
AB  - BACKGROUND AND PURPOSE: Health economic analyses seek to assess the relative
      value (cost vs health benefit trade-offs) of medical technologies. However, these
      methods have been underused in studies of the electrocardiogram (ECG). METHODS:
      We develop a framework for the economic evaluation of the ECG as a decision
      support tool within broader treatment strategies. We then apply this framework to
      the development of an economic study protocol for the Prehospital Wireless
      Transmission of Electrocardiograms to a Cardiologist via a Hand-held Device
      Multicenter study. RESULTS: Our framework defines key cost-effectiveness concepts
      and describes alternative methods for estimating medical costs and health
      benefits. We demonstrate how this framework has been applied to develop the
      Prehospital Wireless Transmission of Electrocardiograms to a Cardiologist via a
      Hand-held Device Multicenter economic protocol. CONCLUSIONS: The conduct of
      health economic studies alongside ECG clinical studies could provide important
      information for those seeking to promote newer ECG applications that require
      significant financial investments.

PMID- 16580428
TI  - A hybrid approach to stabilization and repair of obstructed total anomalous
      pulmonary venous connection in a critically ill newborn infant.

PMID- 16580429
TI  - Effect of patent ductus arteriosus stenting on subsequent bidirectional Glenn
      anastomosis: a word of caution.

PMID- 16580431
TI  - Should cardiac surgery be performed in low-volume hospitals?

PMID- 16580432
TI  - Allocating hearts.

PMID- 16580433
TI  - Stenting the descending aorta during repair of type A dissection: technology
      looking for an application?

PMID- 16580434
TI  - Selective management of the left ventricular outflow tract for repair of
      interrupted aortic arch with ventricular septal defect: management of left
      ventricular outflow tract obstruction.
AB  - OBJECTIVE: Left ventricular outflow tract obstruction remains an early and late
      complication after repair of interrupted aortic arch and ventricular septal
      defect. We reviewed our experience with the selective management of the
      infundibular septum during primary repair to address left ventricular outflow
      tract obstruction. METHODS: From 1991 through 2001, all 27 patients presenting
      with interrupted aortic arch/ventricular septal defect and posterior deviation of
      the infundibular septum were analyzed. Fifteen patients with the smallest
      subaortic areas underwent myectomy or myotomy of the infundibular septum
      concomitant with interrupted aortic arch/ventricular septal defect repair.
      RESULTS: Patients undergoing myectomy-myotomy (Group I) had significantly smaller
      subaortic diameter indexes (0.83 +/- 0.16 cm/m2) when compared with those who had
      only interrupted aortic arch/ventricular septal defect repair (group 2: 0.99 +/-
      0.13 cm/m2, P = .012). Two hospital deaths occurred in group 1, and 1 occurred in
      group 2. No late deaths occurred. No patient in group 2 required reoperation. Six
      group 1 patients required 9 reoperations for left ventricular outflow tract
      obstruction. Five patients underwent resection of a new subaortic membrane. Only
      1 patient had recurrent muscular left ventricular outflow tract obstruction.
      Three patients required a second reoperation, primarily related to aortic valve
      stenosis. CONCLUSIONS: Interrupted aortic arch/ventricular septal defect with
      posterior malalignment of the infundibular septum can be repaired with low
      mortality in the neonatal period. Tailored to the degree of subaortic narrowing,
      resection or incision of the infundibular septum at the time of primary repair
      was very effective in preventing or prolonging the interval to recurrent left
      ventricular outflow tract obstruction compared with the published data. However,
      reoperation for left ventricular outflow tract obstruction, often related to the
      development of a new and discrete subaortic membrane or valvar stenosis, is still
      required in a subset of patients.

PMID- 16580435
TI  - Flow study of an extracardiac connection with persistent left superior vena cava.
AB  - BACKGROUND: Numerous studies have sought to optimize the design of total
      cavopulmonary connections with a single superior vena cava. This study was
      directed to the 2% to 4.5% of the population with dual superior venae cavae,
      investigating the flow fields associated with such total cavopulmonary connection
      anatomies. Additionally, it demonstrates the potential use of computational
      designs and simulations as surgical planning tools. METHODS: A 3-dimensional
      model of a total cavopulmonary connection with bilateral superior venae cavae was
      reconstructed from a patient's magnetic resonance images and investigated
      experimentally and numerically to assess the power losses and flow structures
      within the connection. On the basis of these results, a virtual operation was
      performed in the computer to improve the original connection design. The modified
      anatomy was studied numerically. RESULTS: Because of a smooth connection with an
      extracardiac conduit and no major dimension mismatch between the baffle and the
      connecting vessels, the original anatomy yielded smooth flow fields, low power
      losses, and few disturbances. However, a large offset between the inferior vena
      cava and the left superior vena cava resulted in flow stasis and unbalanced
      hepatic flow distribution. Shifting the inferior vena cava and positioning it
      between the 2 superior venae cavae resulted in a 7% decrease in power losses and
      eliminated the associated flow stasis regions in the main pulmonary artery
      segment. CONCLUSIONS: This study demonstrates the potential use of computer-aided
      design and numeric simulations for surgical planning. It shows that locating the
      inferior vena cava between the superior venae cavae may lead to better-balanced
      lung perfusion. This may require suturing the right and left superior venae cavae
      closer to each other during the hemi-Fontan or Glenn stage.

PMID- 16580436
TI  - Neurodevelopmental outcome after early repair of a ventricular septal defect with
      or without aortic arch obstruction.
AB  - OBJECTIVES: Cross-sectional studies of intermediate-term survivors of infant
      cardiac surgery have revealed a high frequency of neurodevelopmental
      disabilities. Few data exist regarding neurodevelopmental outcome of infants
      undergoing surgical intervention for a ventricular septal defect. The purpose of
      this study was to evaluate the neurodevelopmental outcome at 1 year of age of
      children who had surgical repair in infancy of a ventricular septal defect or a
      ventricular septal defect with aortic arch obstruction. METHODS: Children who
      underwent repair of a ventricular septal defect or single-stage repair of a
      ventricular septal defect with aortic arch obstruction at less than 6 months of
      age were assessed at 1 year of age by using the Bayley Scales of Infant
      Development II, which yields the Mental Development Index and the Psychomotor
      Development Index, both with an expected mean of 100 +/- 15. RESULTS: At 1 year,
      55 patients (ventricular septal defect alone = 36; ventricular septal defect with
      aortic arch obstruction = 19) returned for evaluation. The mean Mental
      Development Index was 92.6 +/- 11.7, with 3 (5%) patients scoring 70 or less. The
      mean Psychomotor Development Index was 86.1 +/- 16.4, with 10 (18%) patients
      scoring 70 or less. Patients with a suspected or confirmed genetic syndrome had
      both a lower Mental Development Index score (P = .011) and a lower Psychomotor
      Development Index score (P = .001). Mental Development Index and Psychomotor
      Development Index were independent of anatomic (specifically aortic arch
      obstruction) and intraoperative factors (specifically deep hypothermic
      circulatory arrest). CONCLUSIONS: Neurodevelopmental outcome at 1 year of age was
      within the normal limits for most patients who underwent repair of a ventricular
      septal defect or a ventricular septal defect with aortic arch obstruction during
      infancy.

PMID- 16580437
TI  - Autologous skeletal myoblast transplantation in patients with nonacute myocardial
      infarction: 1-year follow-up.
AB  - OBJECTIVE: To determine the feasibility and safety of skeletal myoblast
      transplantation in patients with chronic myocardial infarction undergoing
      coronary artery bypass grafting. METHODS: Twelve patients with a previous
      myocardial infarction and ischemic coronary artery disease underwent treatment
      with coronary artery bypass grafting surgery and intramyocardial injection of
      autologous skeletal myoblasts cultured with autologous serum. Global and regional
      cardiac function was assessed by echocardiogram. Fluorine 18 fluorodeoxyglucose
      and nitrogen 13-ammonia positron emission tomography studies were used to
      determine cardiac viability and perfusion. A group of historical control patients
      (n = 14) treated with coronary artery bypass grafting surgery without myoblast
      transplantation was analyzed. RESULTS: The left ventricular ejection fraction
      improved from 35.5% +/- 2.3% (mean +/- SEM) before surgery to 55.1% +/- 8.2% at
      12 months (P < .01) in the myoblast group and from 33.6% +/- 9.3% to 38.6% +/-
      11% in the control group. Regional contractility also improved in the myoblast
      group, particularly in cardiac segments treated with skeletal myoblasts (wall
      motion score index: 3.02 +/- 0.17 at baseline vs 1.36 +/- 0.14 at 12 months; P <
      .0001). Quantitative fluorine 18-fluorodeoxyglucose and nitrogen 13-ammonia
      positron emission tomography showed an increase in viability and perfusion 12
      months after surgery both globally and in segments treated with myoblasts (P =
      .012 and P = .004). Skeletal myoblast implantation was not associated with
      adverse events or an increased incidence of cardiac arrhythmias. CONCLUSIONS: In
      patients with previous myocardial infarction, treatment with skeletal myoblasts
      in conjunction with coronary artery bypass is safe and feasible and is associated
      with an increased global and regional left ventricular function, improvement in
      viability, and perfusion of cardiac tissue and no significant incidence of
      arrhythmias.

PMID- 16580438
TI  - Neurologic outcome after cardiopulmonary bypass with deep hypothermic circulatory
      arrest in rats: description of a new model.
AB  - OBJECTIVE: Neurodevelopmental impairments after repair of congenital heart
      disease with cardiopulmonary bypass and deep hypothermic circulatory arrest
      continue to affect the lives of children. To date, the preclinical investigation
      of cerebral injury mechanisms related to deep hypothermic circulatory arrest has
      been restricted to expensive, personnel-demanding, and cumbersome large-animal
      models without validated neuropsychologic assessment. We aimed to establish a
      rodent recovery model of deep hypothermic circulatory arrest to overcome these
      disadvantages. METHODS: Male rats (n = 34) were cannulated for cardiopulmonary
      bypass, cooled to a rectal temperature of 16 degrees C to 18 degrees C within 30
      minutes, and assigned to deep hypothermic circulatory arrest durations of 0, 45,
      60, 75, 90 (n = 6, respectively), or 105 (n = 4) minutes. After rewarming within
      40 minutes, animals were weaned from cardiopulmonary bypass at 35.5 degrees C.
      Neurologic and cognitive performance was assessed with the modified hole board
      test until postoperative day 14. Thereafter, brains were perfusion fixed and
      histologically analyzed. RESULTS: Logistic regression analyses identified dose
      dependent associations between survival, neurologic or cognitive function, and
      duration of deep hypothermic circulatory arrest. Functional and histologic
      deficits were detectable after clinically relevant deep hypothermic circulatory
      arrest durations. The overall neurologic function did not correlate with
      histologic outcome (r = 0.51, P > .05). CONCLUSIONS: The current study presents a
      novel recovery model of cardiopulmonary bypass with deep hypothermic circulatory
      arrest in the rat. In contrast to studies in large animals, even clinically
      relevant deep hypothermic circulatory arrest durations up to 60 minutes resulted
      in detectable deficits. Consequently, this experimental model appears to be
      suitable to further elucidate the mechanisms associated with adverse cerebral
      outcome after cardiac surgery and deep hypothermic circulatory arrest and to
      investigate potential neuroprotective strategies.

PMID- 16580439
TI  - Pump-induced platelet aggregation with subsequent hypotension: Its mechanism and
      prevention with clopidogrel.
AB  - OBJECTIVES: Use of extracorporeal circuits in cardiopulmonary bypass and
      hemodialysis often causes bleeding problems and hypotension. As shown previously,
      this might be caused by activation of blood platelets due to pumping. The present
      study investigates the mechanism of pump-induced platelet aggregation and its
      possible prevention. METHODS AND RESULTS: Continuous measurement of platelet
      aggregation in an extracorporeal shunt from a carotid to a femoral artery in rats
      showed that aggregation during the first 10 minutes of pumping was not reduced by
      coating the tube with albumin or heparin nor by using dalteparin instead of
      unfractionated heparin as anticoagulant. Also, pump characteristics seemed
      unimportant because aggregation could already be elicited by single tube
      compression with one pump roller. It was calculated that during compression wall
      shear stress in the tube rises far beyond the values known to induce platelet
      aggregation, occurring also in clinically used roller pumps. A crucial role for
      adenosine diphosphate was demonstrated by blockade of platelet adenosine
      diphosphate-P2Y12 receptors with the clinically used drug clopidogrel (50 mg/kg
      intravenously, n = 8). This prevented platelet aggregation and the fall of
      systemic blood pressure (to 71% +/- 12% in controls, n = 6) during 2 hours of
      continuous pumping. CONCLUSION: We conclude that pump-induced platelet
      aggregation is not caused by factors released from the tube or its coating but is
      initiated by short bouts of high shear stress, and its continuation is critically
      dependent on adenosine diphosphate. The latter might have clinical relevance for
      patients connected to extracorporeal systems.

PMID- 16580441
TI  - Tracheostomy after cardiovascular surgery: an assessment of long-term outcome.
AB  - OBJECTIVE: To ascertain long-term survival, identify risk factors for death, and
      document complications of tracheostomy after cardiovascular surgery. METHODS:
      Between January 1, 1998, and September 1, 2001, 188 (1.4%) of 13,191 patients
      undergoing cardiovascular surgery had tracheostomy for respiratory failure 5 to
      79 days (median, 14 days) after surgery. Factors associated with mortality were
      identified in the hazard function domain, and mode of death and complications of
      tracheostomy were determined by follow-up. RESULTS: Survival was 75%, 50%, and
      31% at 30 days, 3 months, and 2 years, respectively. The most important risk
      factors for death were older age (P = .004) and variables representing
      deteriorating hemodynamic (P < .0001), respiratory (P < .0001), and renal (P =
      .0001) function between the index cardiovascular operation and tracheostomy. The
      mode of death was isolated respiratory failure in only 21 (16%) of 130 patients,
      but multisystem organ failure in 71 (55%). Follow-up of 58 survivors identified
      voice complaints in 13 (24%), tracheal stenosis in 5 (9.2%), and permanent
      tracheostomy in 3 (6%). CONCLUSIONS: Only one third of patients undergoing
      tracheostomy after cardiovascular surgery survive, because it is used primarily
      in those with deteriorating function of multiple organ systems. Although
      tracheostomy may enhance patient comfort and simplify nursing care, selection
      algorithms need to be developed if survival is the goal of the intervention.

PMID- 16580440
TI  - Cost-effectiveness of routine mediastinoscopy in computed tomography- and
      positron emission tomography-screened patients with stage I lung cancer.
AB  - OBJECTIVE: Accurate preoperative staging is essential for the optimal management
      of patients with lung cancer. An important goal of preoperative staging is to
      identify mediastinal lymph node metastasis. Computed tomography and positron
      emission tomography may identify mediastinal lymph node metastasis with
      sufficient sensitivity to allow omission of mediastinoscopy. This study utilizes
      our experience with patients with clinical stage I lung cancer to perform a
      decision analysis addressing whether mediastinoscopy should be performed in
      clinical stage I lung cancer patients staged by computed tomography and positron
      emission tomography. METHODS: We retrospectively reviewed our thoracic surgery
      database for cases between May 1999 and May 2004. Patients deemed clinical stage
      I by computed tomography and positron emission tomography were chosen for further
      study. Individual computed tomography, positron emission tomography, and
      operative and pathology reports were reviewed. The postresection pathologic
      staging and long-term survival were recorded. A decision model was created using
      TreeAgePro software and our observed data for the prevalence of mediastinal lymph
      node metastases and for the rate of benign nodules. Data reported in the
      literature were also utilized to complete the decision analysis model. A
      sensitivity analysis of key variables was performed. RESULTS: A total of 248
      patients with clinical stage I lung tumors were identified. One hundred seventy
      eight patients (72%) underwent mediastinoscopy before resection, and 5/178 (3%)
      showed N2 disease. An additional 9 patients were found to have N2 metastasis in
      the final resected specimen, resulting in a total of 14/248 patients (5.6%) with
      occult mediastinal lymph node metastases. Benign nodules were found in 19/248
      (8%) of patients. Decision analysis determined that mediastinoscopy added 0.008
      years of life expectancy at a cost of 250,989 dollars per life-year gained. The
      outcome was sensitive to the prevalence of N2 disease in the population and the
      benefit of induction versus adjuvant therapy for N2 lung cancer. If the
      prevalence of N2 disease exceeds 10%, the sensitivity analysis predicts that
      mediastinoscopy would lengthen life at a cost of less than 100,000 dollars per
      life-year gained. CONCLUSION: Patients with clinical stage I lung cancer staged
      by computed tomography and positron emission tomography benefit little from
      mediastinoscopy. The survival advantage it confers is very small and is dependent
      on the prevalence of N2 metastasis and the unproven superiority of induction
      therapy over adjuvant therapy.

PMID- 16580442
TI  - Is surgical resection indicated for a solitary non-small cell lung cancer
      recurrence?
AB  - OBJECTIVES: Some investigators have reported long-term survival after surgical
      resection of a solitary non-small cell lung cancer recurrence in various sites.
      However, the role and indications of the second operation remain unclear.
      METHODS: We reviewed 28 patients with a solitary recurrence after successful
      initial resection of primary non-small cell lung cancer who underwent resection
      of the recurrent lesion. The clinicopathologic factors associated with outcome
      were analyzed. RESULTS: There were 17 men and 11 women. Recurrence resection was
      performed for the following sites: 16 in the lung, 5 in the brain, 2 in the
      adrenal gland, and 1 each in the chest wall, stomach, skin, pelvic lymph node,
      and malar bone. The median survival time was 25 months, and the 1-, 2-, and 5
      year survival rates after recurrence were 89%, 59%, and 32%, respectively.
      Advanced p-stage (p-stage II and III, n = 14) of the primary tumor was the
      significant negative prognostic factor. Patients with p-stage II or III had
      survival equivalent to that of those who had multiple recurrences or were unfit
      for further surgical intervention. CONCLUSIONS: Resection of a solitary non-small
      cell lung cancer recurrence might provide long-term survival in highly selected
      patients. However, surgical resection might be contraindicated if the primary
      tumor is stage II or III.

PMID- 16580443
TI  - Decellularized heart valve as a scaffold for in vivo recellularization:
      deleterious effects of granulocyte colony-stimulating factor.
AB  - BACKGROUND: Autologous recellularization of decellularized heart valve scaffolds
      is a promising challenge in the field of tissue-engineered heart valves and could
      be boosted by bone marrow progenitor cell mobilization. The aim of this study was
      to examine the spontaneous in vivo recolonization potential of xenogeneic
      decellularized heart valves in a lamb model and the effects of granulocyte colony
      stimulating factor mobilization of bone marrow cells on this process. METHODS:
      Decellularized porcine aortic valves were implanted in 12 lambs. Six lambs
      received granulocyte colony-stimulating factor (10 microg x kg(-1) x d(-1) for 7
      days, granulocyte colony-stimulating factor group), and 6 received no granulocyte
      colony-stimulating factor (control group). Additionally, nondecellularized
      porcine valves were implanted in 5 lambs (xenograft group). Angiographic and
      histologic evaluation was performed at 3, 6, 8, and 16 weeks. RESULTS: Few
      macroscopic modifications of leaflets and the aortic wall were observed in the
      control group, whereas progressive shrinkage and thickening of the leaflets
      appeared in the granulocyte colony-stimulating factor and xenograft groups. In
      the 3 groups progressive ovine cell infiltration (fluorescence in situ
      hybridization) was observed in the leaflets and in the adventitia and the intima
      of the aortic wall but not in the media. Neointimal proliferation of alpha-actin
      positive cells, inflammatory infiltration, adventitial neovascularization, and
      calcifications were more important in the xenograft and the granulocyte colony
      stimulating factor groups than in the control group. Continuous re
      endothelialization appeared only in the control group. CONCLUSION: Decellularized
      xenogeneic heart valve scaffolds allowed partial autologous recellularization.
      Granulocyte colony-stimulating factor led to accelerated heart valve
      deterioration similar to that observed in nondecellularized xenogeneic cardiac
      bioprostheses.

PMID- 16580445
TI  - Midterm results of extensive primary repair of the thoracic aorta by means of
      total arch replacement with open stent graft placement for an acute type A aortic
      dissection.
AB  - OBJECTIVES: We sought to describe the midterm results of extensive primary repair
      of the thoracic aorta by means of the modified elephant trunk technique with a
      stent graft for acute type A aortic dissection, particularly the changes of the
      false lumen shown by enhanced computed tomographic scanning. METHODS: The
      subjects were 35 consecutive patients who received arch replacement with open
      stent grafting for type A acute aortic dissection between December 1997 and April
      2002. The mean follow-up period was 55 months (range, 30-83 months). Computed
      tomographic scanning was performed at 1, 3, 12, and 36 months postoperatively to
      detect thrombosis and obliteration of the false lumen after its exclusion by the
      stent graft. The diameter of the aorta was measured at 3 levels: the distal edge
      of the stent graft, the diaphragm, and the origin of the superior mesenteric
      artery. RESULTS: Two patients died in the initial operation, but no patients
      required additional surgical treatment of the thoracic aorta. The mean diameter
      of the stent grafts was 26.2 mm, and the mean length was 8.9 cm. Thrombus
      formation in the false lumen was recognized at the distal edge of the graft in
      all patients, at the diaphragmatic level in 26 patients, and at the superior
      mesenteric artery level in 15 patients. Obliteration of the false lumen was
      recognized at the distal edge of the graft in all patients, at the diaphragmatic
      level in 20 patients, and at the superior mesenteric artery level in 15 patients.
      The aorta distal to the stent graft showed minimal changes. CONCLUSIONS: In
      patients with acute type A aortic dissections, it is possible to perform
      extensive primary repair of the thoracic aorta with relative safety by using a
      synthetic graft with a self-expanding stent, and this method might reduce the
      necessity of further operations not only for the distal descending aorta but also
      for the thoracoabdominal aorta.

PMID- 16580444
TI  - Magnesium as a neuroprotectant in cardiac surgery: a randomized clinical trial.
AB  - OBJECTIVE: We sought to evaluate magnesium as a neuroprotectant in patients
      undergoing cardiac surgery with cardiopulmonary bypass. METHODS: From February
      2002 to September 2003, 350 patients undergoing elective coronary artery bypass
      grafting, valve surgery, or both were enrolled in a randomized, blinded, placebo
      controlled trial to receive either magnesium sulfate to increase plasma levels
      1(1/2) to 2 times normal during cardiopulmonary bypass (n = 174) or no
      intervention (n = 176). Neurologic function, neuropsychologic function, and
      depression were assessed preoperatively, at 24 and 96 hours after extubation
      (neurologic) and at 3 months (neuropsychologic, depression). Neurologic scores
      were analyzed using ordinal longitudinal methods, and neuropsychologic and
      depression inventory data were summarized by principal component analysis,
      followed by linear regression analysis using component scores as response
      variables. RESULTS: Seven (2%) patients had a postoperative stroke, 2 (1%) in the
      magnesium and 5 (3%) in the placebo group (P = .4). Neurologic score was worse
      postoperatively in both groups (P < .0001); however, magnesium group patients
      performed better than placebo group patients (P = .0001), who had prolonged
      declines in short-term memory and reemergence of primitive reflexes. Three-month
      neuropsychologic performance and depression inventory score were generally better
      than preoperatively, with few differences between groups (P > .6); however, older
      age (P = .0006), previous stroke (P = .003), and lower education level (P =
      .0007) were associated with worse performance. CONCLUSIONS: Magnesium
      administration is safe and improves short-term postoperative neurologic function
      after cardiac surgery, particularly in preserving short-term memory and cortical
      control over brainstem functions. However, by 3 months, other factors and not
      administration of magnesium influence neuropsychologic and depression inventory
      performance.

PMID- 16580446
TI  - Posterior mitral leaflet extension: an adjunctive repair option for ischemic
      mitral regurgitation?
AB  - BACKGROUND: Residual or recurrent mitral regurgitation frequently occurs after
      mitral valve repair for ischemic mitral regurgitation with an annuloplasty ring.
      Because annuloplasty primarily addresses annular dilatation, we studied an
      adjunctive technique that might correct restricted leaflet (Carpentier type IIIb)
      systolic closing motion, which often accompanies annular dilatation in patients
      with ischemic mitral regurgitation. METHODS: Six sheep had radiopaque markers
      placed on the left ventricle, mitral leaflets and annulus, and mitral subvalvular
      apparatus. A pericardial patch was sutured into the middle scallop of the
      posterior mitral valve leaflet and furled in with a reefing stitch placed in the
      radial axis. Posterolateral left ventricular myocardial ischemia was created by
      using proximal circumflex occlusion to induce acute ischemic mitral
      regurgitation. Under open-chest conditions, 3-dimensional marker coordinates were
      measured by using biplane videofluoroscopy at baseline and during acute ischemia
      both before and after release of the reefing stitch (leaflet extension);
      transesophageal echocardiography was used to grade ischemic mitral regurgitation.
      RESULTS: Leaflet apical systolic tethering was not improved by leaflet extension,
      but ischemic mitral regurgitation decreased (control, 0.9 +/- 0.3*; ischemia, 2.4
      +/- 0.3; leaflet extension, 1.5 +/- 0.3; *P < 0.002). Posterior mitral valve
      leaflet midline length (control, 1.45 +/- 0.09*; ischemia, 1.53 +/- 0.10; leaflet
      extension, 1.83 +/- 0.13*; *P < 0.001) and posterior mitral valve leaflet middle
      scallop area (control, 1.66 +/- 0.20 cm2*; ischemia, 1.91 +/- 0.22 cm2; leaflet
      extension, 2.36 +/- 0.22 cm2*; *P < 0.006) increased with leaflet extension
      because of patch unfurling (mean +/- 1 standard error of the mean; repeated
      measures analysis of variance, Dunnet post-hoc test vs ischemia). CONCLUSIONS:
      Posterior mitral valve leaflet extension ameliorated acute ischemic mitral
      regurgitation but did not correct the abnormal apically restricted systolic
      posterior mitral valve leaflet closing motion. This technique might be a useful
      adjunct repair in combination with ring annuloplasty for ischemic mitral
      regurgitation, but the clinical role of this adjunct remains to be defined in
      patients.

PMID- 16580447
TI  - The subcoronary Toronto stentless versus supra-annular Perimount stented
      replacement aortic valve: early clinical and hemodynamic results of a randomized
      comparison in 160 patients.
AB  - BACKGROUND: A stentless valve is expected to be hemodynamically superior to a
      stented valve. The aim of this study was to compare early postoperative
      hemodynamic function and clinical events in a randomized, prospective series of
      160 stentless and stented biological replacement aortic valves. METHODS: We
      randomized 160 consecutive patients on 1 surgeon's list to receive either a
      Toronto stentless porcine valve (St Jude Medical, Inc, St Paul, Minn) or a
      Perimount stented bovine pericardial valve (Edwards Lifesciences, Irvine, Calif).
      Echocardiography was performed at discharge, between 3 and 6 months, and at 1
      year after surgery. Statistical analysis was performed by both intention to treat
      and actual valves implanted. RESULTS: The mean labeled size of both designs of
      valve was 24.7. There were no statistically significant differences in results at
      any time interval or whether analysis was performed by actual valves implanted or
      intention to treat. At 3 to 6 months for the Toronto versus the Perimount valve,
      the effective orifice area was 1.58 versus 1.66 cm2, the mean pressure difference
      was 7.54 versus 7.42 mm Hg, and the peak velocity was 2.07 versus 2.0.1 m/s.
      There was no difference in mortality, regression of left ventricular hypertrophy,
      or complications other than paraprosthetic regurgitation at 12 months or on
      follow-up for a proportion of the sample to 8 years. The incidence of
      regurgitation through the valves was similar for Toronto (10%) and Perimount
      (13.8%) at 1 year, but mild paraprosthetic regurgitation was found in 5 patients
      with the Perimount valve and none with Toronto valves. CONCLUSIONS: There were no
      significant differences in hemodynamic function or clinical events between the
      stented and stentless biological valves chosen for comparison in the early
      postoperative period or in preliminary follow-up to 5 years.

PMID- 16580448
TI  - Stentless bioprostheses improve postoperative coronary flow more than stented
      prostheses after valve replacement for aortic stenosis.
AB  - OBJECTIVE: In some randomized studies, stentless aortic valves have demonstrated
      hemodynamic advantages in comparison with stented prostheses. The effect of more
      physiologic flow dynamics on coronary artery flow has not been investigated yet.
      This study compares coronary perfusion after aortic valve replacement with
      stented or stentless porcine bioprostheses in a prospective randomized study.
      METHODS: A total of 24 patients (73 +/- 6 years) referred for treatment of aortic
      stenosis were randomized to aortic valve replacement with stented (Medtronic
      Mosaic; (Medtronic Inc, Minneapolis, Minn) or stentless (Medtronic Freestyle;
      Medtronic Inc) prostheses. Coronary flow was measured by means of magnetic
      resonance imaging preoperatively, 5 days after the operation, and 6 months
      postoperatively, then with evaluation of coronary flow reserve. Echocardiography
      was performed to quantify transvalvular gradients and left ventricular mass
      regression. RESULTS: Coronary flow increased in both groups significantly (P <
      .001) after aortic valve replacement. This increase was higher in the stentless
      group compared with that seen in the stented group (343 +/- 137 vs 221 +/- 66
      mL/min). Also, coronary flow reserve was higher for stentless valves (3.4 +/- 0.3
      for stentless valves and 2.3 +/- 0.1 for stented valves). Mean pressure gradients
      for Freestyle valves were lower (10 +/- 4 and 8 +/- 3 mm Hg, respectively, vs 19
      +/- 6 postoperatively and 15 +/- 4 mm Hg at follow-up for Mosaic valves, P <
      .05). Left ventricular mass regression was similar in both groups. CONCLUSIONS:
      Normalization of coronary artery flow after aortic valve replacement for aortic
      stenosis was more pronounced for stentless valves compared with stented valves.
      The fact that the stentless design also demonstrated a superior hemodynamic
      performance with lower pressure gradients might be explained by the design being
      closer to physiologic anatomy and thus the presence of lower turbulence levels in
      the sinuses of Valsalva.

PMID- 16580449
TI  - Homing of intravenously infused embryonic stem cell-derived cells to injured
      hearts after myocardial infarction.
AB  - OBJECTIVE: The present study was designed to test whether intravenously infused
      embryonic stem cell-derived cells could translocate to injured myocardium after
      myocardial infarction and improve cardiac function. METHODS: Cultured embryonic
      stem cell-derived cells were transfected with green fluorescent protein.
      Embryonic stem cell-derived cells were administered through the tail vein
      (approximately 10(7) cells in 1 mL of medium for each rat) every other day for 6
      days in 45 rats after myocardial infarction. Six weeks after myocardial
      infarction and cell infusion, cardiac function, blood flow, and the numeric
      density of arterioles were measured to test the benefits of cell therapy. An in
      vitro Transwell assay was performed to evaluate the embryonic stem cell
      migration. RESULTS: Ventricular function, regional blood flow, and arteriole
      density were significantly increased in rats receiving intravenously infused
      embryonic stem cell-derived cells compared with control rats after myocardial
      infarction. Histologic analysis demonstrated that infused embryonic stem cell
      derived cells formed green fluorescent protein-positive grafts in infarcted
      myocardium. Additionally, positive immunostaining for cardiac troponin I was
      found in hearts after myocardial infarction receiving embryonic stem cell-derived
      cell infusion that corresponded to the green fluorescent protein-positive
      staining. The Transwell migration assay indicated that cultured neonatal rat
      cardiomyocytes with overexpression of tumor necrosis factor alpha induced greater
      migration of embryonic stem cells compared with cardiomyocytes without tumor
      necrosis factor alpha expression. CONCLUSIONS: Our data demonstrate that
      intravenously infused embryonic stem cell-derived cells homed to the infarcted
      heart, improved cardiac function, and enhanced regional blood flow at 6 weeks
      after myocardial infarction. The in vitro migration assay suggested that such a
      homing mechanism could be associated with locally released cytokines, such as
      tumor necrosis factor alpha, that are upregulated in the setting of acute
      myocardial infarction and heart failure.

PMID- 16580450
TI  - Antagonizing reactive oxygen by treatment with a manganese (III) metalloporphyrin
      based superoxide dismutase mimetic in cardiac transplants.
AB  - OBJECTIVE: Oxidative stress might be an important factor contributing to injury
      during alloimmune activation. Herein, we evaluated the efficacy of a superoxide
      dismutase mimetic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin
      pentachloride (MnTmPyP), on cytokine gene expression and apoptotic signaling in a
      rat model of cardiac transplantation. METHODS: Lewis-->Lewis (isografts) or
      Wistar-Furth-->Lewis (allografts) heterotopic rat transplants without and with
      treatment with MnTmPyP were used. Reactive oxygen formation was determined on the
      basis of dihydroethidine fluorescence and lucigenin-enhanced chemiluminescence.
      In situ graft function was determined by means of sonomicrometry. Inflammatory
      cytokine, proapoptotic, and antiapoptotic gene expression at either postoperative
      day 4 (early rejection) or postoperative day 6 (late rejection) was determined by
      means of reverse transcriptase polymerase chain reaction. RESULTS: An increased
      production of reactive oxygen in allografts was inhibited to isograft control
      levels by MnTmPyP. MnTmPyP restored either the percentage of fractional
      shortening, the distended diastolic and systolic myocardial segment lengths, or
      both in allografts. Of the increases in cytokine and proapoptotic gene expression
      in allografts, only interleukin 6 was decreased by MnTmPyP. MnTmPyP inhibited
      antiapoptotic gene expression (Bcl-2 and Bcl-xL) during early rejection but
      restored expression at later stages. The increase in activated caspase-3 levels
      in allografts was inhibited by MnTmPyP. CONCLUSIONS: The mechanism of the
      beneficial effect of MnTmPyP on graft function appear related, in part, to
      scavenging O2*- and by decreasing apoptotic signaling rather than an effect on
      inflammatory cytokine gene expression.

PMID- 16580452
TI  - Simultaneous removal of an Amplatzer device from an atrial septal defect and the
      descending aorta.

PMID- 16580451
TI  - Mortality related to cardiac surgery in Brazil, 2000-2003.

PMID- 16580453
TI  - Anomalous left coronary artery arising from the left pulmonary artery, aortic
      coarctation, and a large ventricular septal defect.

PMID- 16580454
TI  - Unusual cardiogenic shock due to pheochromocytoma: recovery after bridge-to
      bridge (extracorporeal life support and DeBakey ventricular assist device) and
      right surrenalectomy.

PMID- 16580455
TI  - Percutaneous occlusion of a pseudoaneurysm evolving after homograft aortic valve
      and root replacement with the Amplatzer muscular ventricular septal defect
      occluder.

PMID- 16580456
TI  - Congenital bronchoesophageal fistula in an adult woman.

PMID- 16580457
TI  - Video-assisted resection of bilateral intralobar pulmonary sequestrations.

PMID- 16580459
TI  - Uniportal video-assisted thoracoscopic surgery pericardial window.

PMID- 16580458
TI  - Intrapericardial colonic herniation.

PMID- 16580460
TI  - A case of ectopic parathyroid hormone production by a pulmonary neoplasm.

PMID- 16580461
TI  - Deterioration and mortality among patients with United Network for Organ Sharing
      status 2 heart disease: caution must be exercised in diverting organs.

PMID- 16580462
TI  - Severe mitral regurgitation after percutaneous transmitral commissurotomy:
      underestimated subvalvular disease.

PMID- 16580464
TI  - FloWatch and pseudoaneurysm: complication versus coincidence.

PMID- 16580465
TI  - Evaluation of a modified ThermoWrap for the Allon warming system in patients
      undergoing elective off-pump coronary artery bypass grafting.

PMID- 16580468
TI  - Unexpected pulmonary embolism in lung transplantation: diagnosis and prospects.

PMID- 16580470
TI  - The times, they are a changin'.

PMID- 16580469
TI  - Use of intravenous immunoglobulin in human disease: a review of evidence by
      members of the Primary Immunodeficiency Committee of the American Academy of
      Allergy, Asthma and Immunology.
AB  - Human immunoglobulin prepared for intravenous administration (IGIV) has a number
      of important uses in the treatment of disease. Some of these are in diseases for
      which acceptable treatment alternatives do not exist. In this review we have
      evaluated the evidence underlying a wide variety of IGIV uses and make specific
      recommendations on the basis of these data. Given the potential risks and
      inherent scarcity of IGIV, careful consideration of the indications for and
      administration of IGIV is warranted.

PMID- 16580472
TI  - Celebrating emergency nurses in India.

PMID- 16580473
TI  - Thank you for article on Edith Cavell by Terri Arthur.

PMID- 16580474
TI  - More on the Hurricane Katrina response.

PMID- 16580475
TI  - Pediatric emergency department recidivism: demographic characteristics and
      diagnostic predictors.
AB  - INTRODUCTION: Overcrowding in emergency departments remains a national problem.
      Increases in patient volume and illness severity are among the factors
      contributing to this crisis. Of particular interest is a small group of patients
      who account for a disproportionate number of ED visits and are known as
      recidivists. Demographic and diagnostic characteristics were examined in an
      attempt to describe this national issue with more clarity. METHODS: The hospital
      decision support system was used to identify 2 readmission indicators (3-month
      return visits and 48-hour returns). Descriptive statistics and multiple
      regression techniques were used to analyze the characteristics of recidivists.
      Chart reviews and telephone interviews were conducted to further explore ED
      utilization. RESULTS: Twenty-five percent of the sample (N = 932) had at least
      one visit during the previous 3 months (N = 237). Four percent of the sample had
      a 48-hour return visit (N = 38). The findings revealed that the traditional
      determinants of ED utilization such as insurance and chronicity of symptoms are
      not reliable predictors of return visits. The risk factors of age, race, and
      diagnosis were significantly associated with return visit at a significance level
      less than .05. The findings confirm that some demographic and diagnostic
      predictability of return visits is indeed evident for pediatric patients.
      DISCUSSION: Although the sample is not representative, the data are helpful in
      identifying some of the issues of pediatric recidivism. Findings provide some
      understanding of parents' utilization of the emergency department and identified
      high-risk pediatric recidivists. Data also revealed specific disease entities
      warranting focused attention, such as nervous system diseases, sense organ
      diseases, digestive system diseases, infectious diseases, and parasitic diseases
      for children younger than 1 year. Patients with these problems may be at greater
      risk for return visits. ED nurses might consider nurse-initiated treatment
      protocols.

PMID- 16580477
TI  - Designing and building a new emergency department: the experience of one chest
      pain, stroke, and trauma center in Columbus, Ohio.

PMID- 16580476
TI  - Pneumatic tube delivery system for blood samples reduces turnaround times without
      affecting sample quality.
AB  - STUDY OBJECTIVES: In this study, blood samples from ED patients that were
      delivered to the laboratory by a pneumatic tube delivery system and by a human
      courier were compared for timeliness and quality of results. METHODS: We studied
      all consecutive measurements of serum hemoglobin and potassium ordered from 2
      emergency departments of a multisite tertiary care hospital system, one with a
      pneumatic tube system and the other using human couriers. Turnaround time was
      measured from the time that the test was ordered by the physician to the time the
      result was reported on the hospital information system. Hemolysis was measured
      with use of a standardized, validated method. ANALYSIS: Times were normalized by
      log transformation (ln [minutes + 1]), and a comparison of sites was conducted
      using analysis of variance. Hemolysis rates of the 2 delivery systems were
      compared by chi2. RESULTS: There was no significant difference in hemolysis rate
      between the 2 methods of delivery (7/121 [5.79%] with a pneumatic tube system and
      20/200 [10%] with a human courier). When delivered with a pneumatic tube system,
      the mean turnaround times (with ranges) for both hemoglobin (33 minutes [4-230])
      and potassium (64 [34-208]) were shorter than those delivered by a human courier
      (43 minutes [3-150] and 72 [28-213], respectively). CONCLUSION: The use of a
      pneumatic tube delivery system for transporting blood samples from the emergency
      department to the laboratory can significantly reduce the turnaround times of
      results without a reduction in sample quality.

PMID- 16580478
TI  - Capnography: considerations for its use in the emergency department.

PMID- 16580479
TI  - Early intervention for the pneumonia patient: an emergency department triage
      protocol.

PMID- 16580480
TI  - Managing body jewelry in emergency situations: misconceptions, patient care, and
      removal techniques.

PMID- 16580481
TI  - A 47-year-old woman with unexplained hemorrhage and change in mental status.

PMID- 16580483
TI  - Triage acuity levels and color.

PMID- 16580484
TI  - Sample medications can be dangerous.

PMID- 16580485
TI  - Grade III degloving injury of the right leg.

PMID- 16580488
TI  - Ketamine: the sedative of choice in a busy pediatric emergency department.

PMID- 16580489
TI  - Button battery ingestions in children.

PMID- 16580490
TI  - Public solicitation of organs on the internet: ethical and policy issues.

PMID- 16580491
TI  - Emergency surgery/trauma physicians: evolution or revolution?

PMID- 16580492
TI  - Strategies to reduce the numbers of patients who leave without being seen.

PMID- 16580493
TI  - Hypofractionated high-dose irradiation for the treatment of malignant
      astrocytomas using simultaneous integrated boost technique by IMRT.
AB  - PURPOSE: We evaluated the clinical significance of hypofractionated high-dose
      irradiation using simultaneous integrated boost technique with intensity
      modulated radiation therapy (IMRT) for the treatment of malignant astrocytomas
      (MAs). METHODS AND MATERIALS: Twenty-five patients with MAs were treated by IMRT.
      Three layered planning target volumes (PTVs) were contoured. PTV-1 was the area
      of enhanced lesion with 5-mm margin; PTV-2 was the area with 15-mm margin
      surrounding the PTV-1; PTV-3 was the area of perifocal edema. Irradiation was
      performed in 8 fractions, and only the dose for PTV-1 was escalated from 48 Gy to
      68 Gy while maintaining the dose for PTV-2 (40 Gy) and PTV-3 (32 Gy). The
      clinical outcome of IMRT was compared with 60 MA patients treated by conventional
      external beam irradiation (EBI). RESULTS: The progression-free survival of
      patients in the IMRT group was significantly longer than that in the EBI group (p
      < 0.0001). No distant failure was observed in both groups. In the IMRT group,
      dissemination was the most frequent cause of death (70%). The overall survival of
      patients in the IMRT group was better than that in the EBI group (p = 0.043).
      CONCLUSIONS: Our regimen of IMRT contributed to the control of both the regional
      and infiltrating tumors, resulting in better survival of patients.

PMID- 16580494
TI  - Combined proton and photon irradiation for craniopharyngioma: long-term results
      of the early cohort of patients treated at Harvard Cyclotron Laboratory and
      Massachusetts General Hospital.
AB  - PURPOSE: We report the results of the early cohort of patients treated for
      craniopharyngioma with combined proton-photon irradiation at the Massachusetts
      General Hospital and the Harvard Cyclotron Laboratory. METHODS AND MATERIALS:
      Between 1981 and 1988, 15 patients with craniopharyngioma were treated in part or
      entirely with fractionated 160 MeV proton beam therapy. The group consisted of 5
      children (median age, 15.9 years) and 10 adults (median age, 36.2 years). Median
      dose prescribed to the tumor was 56.9 cobalt Gray equivalent (CGE; 1 proton Gray
      = 1.1 CGE). The median proton component was 26.9 CGE. Patients were treated after
      documented recurrence after initial surgery (n = 6) or after subtotal resection
      or biopsy (n = 9). None had had prior radiation therapy. RESULTS: Median
      observation period of surviving patients (n = 11) was 13.1 years from
      radiotherapy. One patient was lost to follow-up with tumor control after 5.2
      years. Actuarial 10-year survival rate was 72%. Four patients have died 5-9.1
      years after treatment, two from local failure. Actuarial 5- and 10-year local
      control rates were 93% and 85%, respectively. The functional status of the living
      adult patients is unaltered from their preradiotherapy status; all of them
      continued leading normal or near normal working lives. None of the patients
      treated as a child had experienced recurrence of tumor. One child shows learning
      difficulties and slight retardation, comparable to his preradiotherapy status.
      The others have professional achievements within the normal range. CONCLUSION:
      Results in terms of survival and local control are comparable with other
      contemporary series. Although no formal neuropsychological testing was performed,
      the surrogate measures of lifestyle and professional accomplishments appear to be
      satisfactory.

PMID- 16580495
TI  - Proton beam therapy for invasive bladder cancer: a prospective study of bladder
      preserving therapy with combined radiotherapy and intra-arterial chemotherapy.
AB  - PURPOSE: To present outcomes of bladder-preserving therapy with proton beam
      irradiation in patients with invasive bladder cancer. METHODS AND MATERIALS:
      Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2
      3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic
      X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and
      cisplatin. Upon completion of these treatments, patients were evaluated by
      transurethral resection biopsy. Patients with no residual tumor received proton
      irradiation boost to the primary sites, whereas patients demonstrating residual
      tumors underwent radical cystectomy. RESULTS: Of 25 patients, 23 (92%) were free
      of residual tumor at the time of re-evaluation; consequently, proton beam therapy
      was applied. The remaining 2 patients presenting with residual tumors underwent
      radical cystectomy. Of the 23 patients treated with proton beam therapy, 9
      experienced recurrence at the median follow-up time of 4.8 years: local
      recurrences and distant metastases in 6 and 2 patients, respectively, and both
      situations in 1. The 5-year overall, disease-free, and cause-specific survival
      rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder
      preservation rates were 73% and 96%, respectively, in the patients treated with
      proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9
      patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic
      cystitis in 2. CONCLUSIONS: The present bladder-preserving regimen for invasive
      bladder cancer was feasible and effective. Proton beam therapy might improve
      local control and facilitate bladder preservation.

PMID- 16580496
TI  - Systematic evaluation of MRI findings in different stages of treatment of
      cervical cancer: potential of MRI on delineation of target, pathoanatomic
      structures, and organs at risk.
AB  - PURPOSE: To compare magnetic resonance imaging (MRI) findings at different stages
      of cervix cancer treatment and to define the potential of MRI to delineate the
      gross tumor volume (GTV), clinical target volume (CTV), pathoanatomic structures,
      and organs at risk (OAR) in brachytherapy. METHODS AND MATERIALS: Forty-nine
      patients underwent MRI at diagnosis and at brachytherapy. The ability to
      discriminate anatomic structures on MRI was assessed (quality factor: 0 =
      inability to discriminate; 1 = fair discrimination; 2 = good discrimination; 3 =
      excellent discrimination). The overall ability to visualize (percentage of
      patients with quality factors greater than 0) and the overall discrimination
      quality score (mean quality factors of all patients) were estimated for the
      applicator, GTV at diagnosis (GTV(D)), GTV at brachytherapy (GTV(BT))/"gray
      zones," cervix rim/uterine corpus, OAR, vaginal wall, and parametria. RESULTS:
      The overall ability to visualize the applicator on MRI at brachytherapy was 100%;
      for the GTV(BT)/"gray zones," cervix rim/uterine corpus, OAR, and vaginal wall,
      visualization was 98% (overall discrimination quality factors: 1.2, 2.9, 2.1,
      1.9, 1.7, and 2.6). Three of 4 borders of parametrial space were defined in more
      than 98% (discrimination quality factors: 2.9, 2.1, and 1.2). CONCLUSION:
      Magnetic resonance imaging provides appropriate information for definition of the
      applicator, GTV, CTV, pathoanatomic structures, and OAR that enables precise
      delineation for cervix cancer brachytherapy.

PMID- 16580497
TI  - A modified inflammatory bowel disease questionnaire and the Vaizey Incontinence
      questionnaire are more sensitive measures of acute gastrointestinal toxicity
      during pelvic radiotherapy than RTOG grading.
AB  - PURPOSE: Simple scales with greater sensitivity than Radiation Therapy Oncology
      Group (RTOG) grading to detect acute gastrointestinal toxicity during pelvic
      radiotherapy, could be clinically useful. METHODS AND MATERIALS: Do
      questionnaires used in benign gastrointestinal diseases detect toxicity in
      patients undergoing radiotherapy? The patient-completed Inflammatory Bowel
      Disease (IBDQ) and Vaizey Incontinence questionnaires were compared prospectively
      at baseline and at Week 5 to physician-completed RTOG grading. RESULTS: A total
      of 107 patients, median age 63 years, were recruited. After 5 weeks of treatment,
      patients with gynecologic and gastrointestinal cancer were more symptomatic than
      urologic patients (p = 0.012; p = 0.014). Overall, 94% had altered bowel habits,
      80% loose stool, 74% frequency, 65% difficult gas, 60% pain, >48% distress, 44%
      tenesmus, >40% restrictions in daily activity, 39% urgency, 37% fecal
      incontinence, and 40% required antidiarrheal medication. The median RTOG score
      was 1 (range, 0-2), median IBDQ score 204.5 (range, 74-224), and median Vaizey
      score 5 (range, 0-20). Chemotherapy preceding radiotherapy increased fecal
      incontinence (p = 0.002). RTOG scores stabilized after 3 weeks, IBDQ scores
      peaked at Week 4, and Vaizey scores worsened throughout treatment. IBDQ and
      Vaizey scores distinguished between groups with different RTOG scores.
      CONCLUSION: The IBDQ and Vaizey questionnaires are reliable and sensitive,
      offering greater insight into the severity and range of symptoms compared with
      RTOG grading.

PMID- 16580498
TI  - Enhanced radiosensitization of p53 mutant cells by oleamide.
AB  - PURPOSE: Effect of oleamide, an endogenous fatty-acid primary amide, on tumor
      cells exposed to ionizing radiation (IR) has never before been explored. METHODS
      AND MATERIALS: NCI H460, human lung cancer cells, and human astrocytoma cell
      lines, U87 and U251, were used. The cytotoxicity of oleamide alone or in
      combination with IR was determined by clonogenic survival assay, and induction of
      apoptosis was estimated by FACS analysis. Protein expressions were confirmed by
      Western blotting, and immunofluorescence analysis of Bax by use of confocal
      microscopy was also performed. The combined effect of IR and oleamide to suppress
      tumor growth was studied by use of xenografts in the thighs of nude mice.
      RESULTS: Oleamide in combination with IR had a synergistic effect that decreased
      clonogenic survival of lung-carcinoma cell lines and also sensitized xenografts
      in nude mice. Enhanced induction of apoptosis of the cells by the combined
      treatment was mediated by loss of mitochondrial membrane potential, which
      resulted in the activation of caspase-8, caspase-9, and caspase-3 accompanied by
      cytochrome c release and Bid cleavage. The synergistic effects of the combined
      treatment were more enhanced in p53 mutant cells than in p53 wild-type cells. In
      p53 wild-type cells, both oleamide and radiation induced Bax translocation to
      mitochondria. On the other hand, in p53 mutant cells, radiation alone slightly
      induced Bax translocation to mitochondria, whereas oleamide induced a larger
      translocation. CONCLUSIONS: Oleamide may exhibit synergistic radiosensitization
      in p53 mutant cells through p53-independent Bax translocation to mitochondria.

PMID- 16580500
TI  - Relation between radiation-induced whole lung functional loss and regional
      structural changes in partial irradiated rat lung.
AB  - PURPOSE: Radiation-induced pulmonary toxicity is characterized by dose, region,
      and time-dependent severe changes in lung morphology and function. This study
      sought to determine the relation between the structural and functional changes in
      the irradiated rat lung at three different phases after irradiation. MATERIALS
      AND METHODS: Six groups of animals were irradiated to 16-22 Gy to six different
      lung regions, each containing 50% of the total lung volume. Before and every 2
      weeks after irradiation, the breathing rate (BR) was measured, and at Weeks 8,
      26, and 38 CT was performed. From the computed tomography scans, the irradiated
      lung tissue was delineated using a computerized algorithm. A single quantitative
      measure for structural change was derived from changes of the mean and standard
      deviation of the density within the delineated lung. Subsequently, this was
      correlated with the BR in the corresponding phase. RESULTS: In the mediastinal
      and apex region, the BR and computed tomography density changes did not correlate
      in any phase. After lateral irradiation, the density changes always correlated
      with the BR; however, in all other regions, the density changes only correlated
      significantly (r(2) = 0.46-0.85, p < 0.05) with the BR in Week 26. CONCLUSION:
      Changes in pulmonary function correlated with the structural changes in the
      absence of confounding heart irradiation.

PMID- 16580499
TI  - Tumor-specific apoptotic gene targeting overcomes radiation resistance in
      esophageal adenocarcinoma.
AB  - PURPOSE: To overcome radiation resistance in esophageal adenocarcinoma by tumor
      specific apoptotic gene targeting using tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL). METHODS AND MATERIALS: Adenoviral vector Ad/TRAIL-F/RGD
      with a tumor-specific human telomerase reverse transcription promoter was used to
      transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung
      fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot,
      fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal
      adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL
      F/RGD plus local radiotherapy. RESULTS: The combination of Ad/TRAIL-F/RGD and
      radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma
      cell lines but not in NHLF cells. This combination also significantly reduced
      clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid
      accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL
      F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8,
      and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro
      and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically
      inhibited tumor growth and prolonged mean survival in the esophageal
      adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5
      days for Ad/TRAIL-F/RGD alone (p < 0.05). CONCLUSIONS: The combination of tumor
      specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing
      esophageal adenocarcinoma growth and prolonging survival.

PMID- 16580501
TI  - Preclinical evaluation of erythropoietin administration in a model of radiation
      induced kidney dysfunction.
AB  - PURPOSE: To test whether the clinically available growth factor erythropoietin
      (EPO) influences radiation-induced normal-tissue damage in a model of kidney
      dysfunction. METHODS: Animal experiments were conducted to test the role of EPO
      administration in a C3H mouse model of unilateral kidney irradiation with 6, 8,
      and 10 Gy and to assess the effects of 2 different dose levels of EPO. The kidney
      function was assessed before radiotherapy, as well as 19, 25, 31, and 37 weeks
      thereafter by means of (99m)Tc-dimercaptosuccinat scans (static scintigraphy).
      RESULTS: Concomitant EPO administration significantly increased the degree of
      radiation-induced kidney dysfunction. A dose of 2,000 IU/kg body weight per
      injection tended to cause more damage than the lower dose of 500 IU/kg.
      CONCLUSION: Administration of growth factors concomitant to radiotherapy might
      modify the development of kidney dysfunction. Although insulin-like growth factor
      1 has previously been shown to protect the kidney, such an effect could not be
      demonstrated for EPO. The latter agent even increased the development of
      nephropathy.

PMID- 16580502
TI  - In vivo two-photon microscopy study of short-term effects of microbeam
      irradiation on normal mouse brain microvasculature.
AB  - PURPOSE: The purpose of this study was to assess the early effects of microbeam
      irradiation on the vascular permeability and volume in the parietal cortex of
      normal nude mice using two-photon microscopy and immunohistochemistry. METHODS
      AND MATERIALS: The upper part of the left hemisphere of 55 mice was irradiated
      anteroposteriorly using 18 vertically oriented beams (width 25 microm,
      interdistance 211 microm; peak entrance doses: 312 or 1000 Gy). At different
      times after microbeam exposure, the microvasculature in the cortex was analyzed
      using intravital two-photon microscopy after intravascular injection of
      fluorescein isothiocyanate (FITC)-dextrans and sulforhodamine B (SRB). Changes of
      the vascular volume were observed at the FITC wavelength over a maximum depth of
      650 mum from the dura. The vascular permeability was detected as extravasations
      of SRB. RESULTS: For all times (12 h to 1 month) after microbeam irradiation and
      for both doses, the FITC-dextran remained in the vessels. No significant change
      in vascular volume was observed between 12 h and 3 months after irradiation.
      Diffusion of SRB was observed in microbeam irradiated regions from 12 h until 12
      days only after a 1000 Gy exposure. CONCLUSION: No radiation damage to the
      microvasculature was detected in normal brain tissue after a 312 Gy microbeam
      irradiation. This dose would be more appropriate than 1000 Gy for the treatment
      of brain tumors using crossfired microbeams.

PMID- 16580503
TI  - Regulation of early and delayed radiation responses in rat small intestine by
      capsaicin-sensitive nerves.
AB  - PURPOSE: Mast cells protect against the early manifestations of intestinal
      radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal
      sensory nerves are closely associated with mast cells, both anatomically and
      functionally, and serve an important role in the regulation of mucosal
      homeostasis. This study examined the effect of sensory nerve ablation on the
      intestinal radiation response in an established rat model. METHODS AND MATERIALS:
      Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks
      later, a localized segment of ileum was X-irradiated or sham irradiated.
      Structural, cellular, and molecular changes were examined 2 weeks (early injury)
      and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the
      effect of sensory nerve ablation on intestinal radiation injury was assessed
      using c-kit mutant (Ws/Ws) mast cell-deficient rats. RESULTS: Capsaicin treatment
      caused a baseline reduction in mucosal mast cell density, crypt cell
      proliferation, and expression of substance P and calcitonin gene-related peptide,
      two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly
      exacerbated early intestinal radiation toxicity (loss of mucosal surface area,
      inflammation, intestinal wall thickening), but attenuated the development of
      chronic intestinal radiation fibrosis (collagen I accumulation and transforming
      growth factor beta immunoreactivity). In mast cell-deficient rats, capsaicin
      treatment exacerbated postradiation epithelial injury (loss of mucosal surface
      area), but none of the other aspects of radiation injury were affected by
      capsaicin treatment. CONCLUSIONS: Ablation of capsaicin-sensitive enteric neurons
      exacerbates early intestinal radiation toxicity, but attenuates development of
      chronic fibroproliferative changes. The effect of capsaicin treatment on the
      intestinal radiation response is partly mast cell dependent.

PMID- 16580504
TI  - Tumor motion and deformation during external radiotherapy of bladder cancer.
AB  - PURPOSE: First, to quantify bladder-tumor motion in 3 dimensions during a 4-week
      to 5-week course of external radiotherapy. Second, to relate the motion to the
      tumor location on the bladder wall. Third, to extensively evaluate gross tumor
      volume (GTV) shape and volume changes during the course of the treatment. METHODS
      AND MATERIALS: Multiple repeat computed tomography (CT) images were obtained for
      21 bladder cancer patients. These scans were matched to the rigid bony anatomy.
      For each patient, the main direction and magnitude of the tumor movement was
      determined by use of principle-component analysis. To study GTV shape changes,
      all GTVs were registered to the GTV in the planning CT scan, and the residual
      shape errors were determined by measurement of edge variations perpendicular to
      the median surface. RESULTS: Gross tumor volume translations were largest in
      cranial-caudal and anterior-posterior direction (SD, 0.1 to approximately 0.9
      cm). The translations were strongly correlated with the tumor location on the
      bladder wall. The average value of the local standard deviations of the GTV shape
      ranged from 0.1 to approximately 0.35 cm. CONCLUSIONS: Despite large differences
      in bladder filling, variations in GTV shape were small compared with variations
      in GTV position. Geometric uncertainties in the GTV position depended strongly on
      the tumor location on the bladder wall.

PMID- 16580505
TI  - Multiple regions-of-interest analysis of setup uncertainties for head-and-neck
      cancer radiotherapy.
AB  - PURPOSE: To analyze three-dimensional setup uncertainties for multiple regions of
      interest (ROIs) in head-and-neck region. METHODS AND MATERIALS: In-room computed
      tomography (CT) scans were acquired using a CT-on-rails system for 14 patients.
      Three separate bony ROIs were defined: C2 and C6 vertebral bodies and the
      palatine process of the maxilla. Translational shifts of 3 ROIs were calculated
      relative to the marked isocenter on the immobilization mask. RESULTS: The shifts
      for all 3 ROIs were highly correlated. However, noticeable differences on the
      order of 2-6 mm existed between any 2 ROIs, indicating the flexibility and/or
      rotational effect in the head-and-neck region. The palatine process of the
      maxilla had the smallest right-left shifts because of the tight lateral fit in
      the face mask, but the largest superior-inferior movement because of in-plane
      rotation and variations in jaw positions. The neck region (C6) had the largest
      right-left shifts. The positioning mouthpiece was found effective in reducing
      variations in the superior-inferior direction. There was no statistically
      significant improvement for using the S-board (8 out of 14 patients) vs. the
      short face mask. CONCLUSIONS: We found variability in setup corrections for
      different regions of head-and-neck anatomy. These relative positional variations
      should be considered when making setup corrections or designing treatment
      margins.

PMID- 16580506
TI  - An estimation of radiobiologic parameters from clinical outcomes for radiation
      treatment planning of brain tumor.
AB  - PURPOSE: To estimate a plausible set of radiobiologic parameters such as alpha,
      alpha/beta values, from clinical outcomes for biologically based radiation
      treatment planning of brain tumors. METHODS AND MATERIALS: Linear-quadratic (LQ)
      formalism and the concept of equivalent uniform dose were used to analyze a
      series of published clinical data for malignant gliomas involving different forms
      of radiation therapy. RESULTS: A plausible set of LQ parameters was obtained for
      gliomas: alpha = 0.06 +/- 0.05 Gy(-1), alpha/beta = 10.0 +/- 15.1 Gy, the tumor
      cell doubling time T(d) = 50 +/- 30 days, with the repair half-time of 0.5 h. The
      present estimated biologic parameters can reasonably predict the effectiveness of
      most of the recently reported clinical results employing either single or
      combined radiation therapy modalities. Different LQ parameters between Grade 3
      and Grade 4 astrocytomas were found, implying the radiosensitivity for different
      grade tumors may be different. Smaller alpha, beta from in vivo was observed,
      indicating lower radiosensitivity occurred in vivo as compared with in vitro.
      CONCLUSIONS: A plausible set of radiobiologic parameters for gliomas was
      estimated based on clinical data. These parameters can reasonably predict most of
      the clinical results. They may be used to design new treatment fractionation
      schemes and to evaluate and optimize treatment plans.

PMID- 16580507
TI  - Uncertainty in treatment of head-and-neck tumors by use of intraoral mouthpiece
      and embedded fiducials.
AB  - PURPOSE: To reduce setup error and intrafractional movement in head-and-neck
      treatment, a real-time tumor tracking radiotherapy (RTRT) system was used with
      the aid of gold markers implanted in a mouthpiece. METHODS AND MATERIALS: Three 2
      mm gold markers were implanted into a mouthpiece that had been custom made for
      each patient before the treatment planning process. Setup errors in the
      conventional immobilization system using the shell (manual setup) and in the RTRT
      system (RTRT setup) were compared. Eight patients with pharyngeal tumors were
      enrolled. RESULTS: The systematic setup errors were 1.8, 1.6, and 1.1 mm in the
      manual setup and 0.2, 0.3, and 0.3 mm in the RTRT setup in right-left,
      craniocaudal, and AP directions, respectively. Statistically significant
      differences were observed with respect to the variances in setup error (p
      <0.001). The systematic and random intrafractional errors were maintained within
      the ranges of 0.2-0.6 mm and 1.0-2.0 mm, respectively. The rotational systematic
      and random intrafractional errors were estimated to be 2.2-3.2 degrees and 1.5
      1.6 degrees , respectively. CONCLUSIONS: The setup error and planning target
      volume margin can be significantly reduced using an RTRT system with a mouthpiece
      and three gold markers.

PMID- 16580508
TI  - Four-dimensional proton treatment planning for lung tumors.
AB  - PURPOSE: In proton radiotherapy, respiration-induced variations in density lead
      to changes in radiologic path lengths and will possibly result in geometric
      misses. We compared different treatment planning strategies for lung tumors that
      compensate for respiratory motion. METHODS AND MATERIALS: Particle-specific
      treatment planning margins were applied to standard helical computed tomography
      (CT) scans as well as to "representative" CT scans. Margins were incorporated
      beam specific laterally by aperture widening and longitudinally by compensator
      smearing. Furthermore, treatment plans using full time-resolved 4D-computed
      tomography data were generated. RESULTS: Four-dimensional treatment planning
      guaranteed target coverage throughout a respiratory cycle. Use of a standard
      helical CT data set resulted in underdosing the target volume to 36% of the
      prescribed dose. For CT data representing average target positions, coverage can
      be expected but not guaranteed. In comparison to this strategy, 4D planning
      decreased the mean lung dose by up to 16% and the lung volume receiving 20 Gy
      (prescribed target dose 72 Gy) by up to 15%. CONCLUSION: When the three planning
      strategies are compared, only 4D proton treatment planning guarantees delivery of
      the prescribed dose throughout a respiratory cycle. Furthermore, the 4D planning
      approach results in equal or reduced dose to critical structures; even the
      ipsilateral lung is spared.

PMID- 16580509
TI  - Geometric and dosimetric evaluations of an online image-guidance strategy for 3D
      CRT of prostate cancer.
AB  - PURPOSE: To evaluate an online image-guidance strategy for conformal treatment of
      prostate cancer and to estimate margin-reduction benefits. METHODS AND MATERIALS:
      Twenty-eight patients with at least 16 helical computed tomography scans were
      each used in this study. Two prostate soft-tissue registration methods, including
      sagittal rotation, were evaluated. Setup errors and rigid organ motion were
      corrected online; non-rigid and intrafraction motion were included in offline
      analysis. Various clinical target volume-planning target volume (CTV-PTV) margins
      were applied. Geometrical evaluations included analyses of isocenter shifts and
      rotations and overlap index. Dosimetric evaluations included minimum dose and
      equivalent uniform dose (EUD) for prostate and gEUD for rectum. RESULTS: Average
      isocenter shift and rotation were (dX,dY,dZ,theta) = (0.0 +/- 0.7,-1.1 +/- 4.0,
      0.1 +/- 2.5,0.7 degrees +/- 2.0 degrees ) mm. Prostate motion in anterior
      posterior (AP) direction was significantly higher than superior-inferior and left
      right (LR) directions. This observation was confirmed by isocenter shift in
      perspectives AP (1.8 +/- 1.8 mm) and RL (3.7 +/- 3.0 mm). Organ motion degrades
      target coverage and reduces doses to rectum. If 2% dose reduction on prostate
      D(99) is allowed for 90% patients, then minimum 3 mm margins are necessary with
      ideal image registration. CONCLUSIONS: Significant margin reduction can be
      achieved through online image guidance. Certain margins are still required for
      nonrigid and intrafraction motion. To further reduce margin, a strategy that
      combines online geometric intervention and offline dose replanning is necessary.

PMID- 16580510
TI  - In regard to Ciernik et al.: Automated functional image-guided radiation
      treatment planning for rectal cancer (Int J Radiat Oncol Biol Phys 2005;62:893
      900).

PMID- 16580512
TI  - A permanent breast seed implant as partial-breast radiation therapy for early
      stage patients: in regards to Keller et al. (Int J Radiat Oncol Biol Phys
      2005;62:358-365).

PMID- 16580514
TI  - In regard to Litzenberg et al.: Retrospective analysis of prostate patients with
      implanted gold markers using off-line and adaptive therapy protocols (Int J
      Radiat Oncol Biol Phys 2005;63:123-133).

PMID- 16580516
TI  - Measurement of strain and strain rate by echocardiography: ready for prime time?
AB  - Strain and strain rate (SR) are measures of deformation that are basic
      descriptors of both the nature and the function of cardiac tissue. These
      properties may now be measured using either Doppler or two-dimensional ultrasound
      techniques. Although these measurements are feasible in routine clinical
      echocardiography, their acquisition and analysis nonetheless presents a number of
      technical challenges and complexities. Echocardiographic strain and SR imaging
      has been applied to the assessment of resting ventricular function, the
      assessment of myocardial viability using low-dose dobutamine infusion, and stress
      testing for ischemia. Resting function assessment has been applied in both the
      left and the right ventricles, and may prove particularly valuable for
      identifying myocardial diseases and following up the treatment response. Although
      the evidence base is limited, SR imaging seems to be feasible and effective for
      the assessment of myocardial viability. The use of the technique for the
      detection of ischemia during stress echocardiography is technically challenging
      and likely to evolve further. The clinical availability of strain and SR
      measurement may offer a solution to the ongoing need for quantification of
      regional and global cardiac function. Nonetheless, these techniques are
      susceptible to artifact, and further technical development is necessary.

PMID- 16580517
TI  - Molecular and cellular imaging of atherosclerosis: emerging applications.
AB  - Molecular imaging studies have shed light on important biological aspects of
      atherosclerosis, and are now entering the clinical arena for the detection of
      clinical atheroma. This review first discusses fundamental principles regarding
      the rationale for and development of molecular imaging technologies for
      investigating atherosclerosis. Next, we highlight clinically promising imaging
      strategies that illuminate key biological aspects of atherosclerosis, including
      macrophage activity, protease activity, lipoprotein presence, apoptosis, and
      angiogenesis. We envision that several molecular imaging approaches will become
      important adjuncts to the clinical management of high-risk atherosclerosis.

PMID- 16580518
TI  - ST-segment elevation myocardial infarction: recommendations on triage of patients
      to heart attack centers: is it time for a national policy for the treatment of ST
      segment elevation myocardial infarction?
AB  - Despite substantial progress in the diagnosis and treatment of acute ST-segment
      elevation myocardial infarction (STEMI), implementation of this knowledge into
      routine clinical practice has been variable. It has become increasing clear that
      primary percutaneous coronary intervention (PCI) is the preferred method of
      reperfusion if it can be performed in a timely manner. Recent European data
      suggest that transfer for direct PCI may also be preferable to fibrinolytic
      therapy. We believe it is time to establish a national policy for treatment of
      patients with STEMI to develop a coordinated system of care similar to that of
      the level 1 trauma system.

PMID- 16580519
TI  - Regionalization of ST-segment elevation acute coronary syndromes care: putting a
      national policy in proper perspective.
AB  - A uniform policy for regionalization of ST-segment elevation myocardial
      infarction (STEMI) care raises several concerns. Transferring all STEMI patients
      to obtain primary percutaneous coronary intervention (PCI) may be less effective
      than transferring only high-risk STEMI patients. Delays in time to treatment >60
      min associated with transferring patients for primary PCI may result in increased
      mortality for the average patient as compared with providing immediate
      fibrinolytic therapy at their initial hospital; yet more than 95% of patients
      transferred for primary PCI in the U.S. exceed this 60-min benchmark. Superior
      outcomes associated with treatment at higher-volume regional STEMI centers are
      inconsistent among centers, and there is no direct evidence that patients will
      benefit by a transfer to a high-volume hospital from a low-volume hospital.
      Published data suggest as many as 800 PCI patients would need to be transferred
      to a high-volume PCI hospital to avoid a single death at a low-volume PCI
      hospital. Although European randomized trial data suggest transferring patients
      with STEMI for primary PCI may be superior to immediate fibrinolytic therapy,
      these findings are unlikely to generalize to the U.S. health care system given
      size, geography, and organization. ST segment elevation myocardial infarction
      care regionalization would require a massive redistribution of health care
      resources, depriving several hospitals of advanced cardiac care facilities,
      expertise, and associated revenue. Clearer evidence of the benefits and
      discussion of potential harms are needed before adopting a national STEMI
      regionalization policy.

PMID- 16580521
TI  - Sirolimus-eluting stents remain superior to bare-metal stents at two years:
      medium-term results from the Rapamycin-Eluting Stent Evaluated at Rotterdam
      Cardiology Hospital (RESEARCH) registry.
AB  - OBJECTIVES: The purpose of this study was to investigate the medium-term (two
      year) outcome of the unrestricted utilization of sirolimus-eluting stents (SES)
      in an all-comer population. BACKGROUND: Despite the implantation of SES in over a
      million patients to date, limited data exist on long-term outcomes. METHODS:
      Sirolimus-eluting stents were used as the default strategy as part of the
      Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH)
      registry. A total of 508 consecutive patients with de novo lesions exclusively
      treated with SES were compared with 450 patients who received bare stents in the
      immediately preceding period (pre-SES group). RESULTS: Patients in the SES group
      more frequently had multivessel disease, more type C lesions, received more
      stents, and had more bifurcation stenting. At two years, the cumulative rate of
      major adverse cardiac events (death, myocardial infarction, or target vessel
      revascularization) was 15.4% in the SES group and 22.0% in the pre-SES group
      (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.50 to 0.91; p = 0.01).
      The two-year risk of target vessel revascularization in the SES group and in the
      pre-SES group was 8.2% and 14.8%, respectively (HR 0.53, 95% CI 0.36 to 0.79; p =
      0.002). CONCLUSIONS: In an unrestricted population, the beneficial effects of
      sirolimus-eluting stent implantation extend out to two years compared with bare
      metal stents, driven by a reduction in re-intervention rates. These findings
      should be confirmed by the results of the large randomized trials.

PMID- 16580520
TI  - Two-year outcomes after sirolimus-eluting stent implantation: results from the
      Sirolimus-Eluting Stent in de Novo Native Coronary Lesions (SIRIUS) trial.
AB  - OBJECTIVES: The purpose of this study was to examine the two-year clinical
      outcomes in patients enrolled in the Sirolimus-Eluting Stent in De Novo Native
      Coronary Lesions (SIRIUS) study. BACKGROUND: The SIRIUS study was a double
      blinded randomized study which demonstrated that sirolimus-eluting stents (SES)
      significantly improved angiographic results (at 8 months) and clinical outcomes
      (at 9 and 12 months) compared with bare-metal stents (BMS). METHODS: Patients
      with de novo native coronary artery lesions randomized to either SES (533
      patients) or control BMS (525 patients) were followed for two years. RESULTS:
      Between one and two years, there were infrequent additional clinical events that
      were equally distributed between the sirolimus and control groups. After two
      years, target lesion revascularization was 5.8% and 21.3% in SES and control
      patients, respectively (p < 0.001), and major adverse cardiovascular events and
      target vessel failure rates were 10.1% versus 24.4% and 12.0% versus 26.7%,
      respectively (p < 0.0001 for both). There were no differences in death,
      myocardial infarction, and stent thrombosis between the two groups. CONCLUSIONS:
      Clinical outcomes two years after implantation of SES continue to demonstrate
      significant reduction in the need for repeat target lesion (and vessel)
      revascularization compared with BMS without evidence for either disproportionate
      late restenosis or late stent thrombosis.

PMID- 16580522
TI  - Drug-eluting stents are safe and effective: right or wrong?

PMID- 16580523
TI  - Remodeling index compared to actual vascular remodeling in atherosclerotic left
      main coronary arteries as assessed with long-term (> or =12 months) serial
      intravascular ultrasound.
AB  - OBJECTIVES: We present the remodeling index (RI) versus serial intravascular
      ultrasound (IVUS) data. BACKGROUND: The RI, derived by comparing lesion external
      elastic membrane (EEM) cross-sectional area versus the reference at one time
      point, is used in various IVUS studies as a substitute of true remodeling (change
      in EEM over time), assuming that it represents true remodeling. METHODS: We
      studied 46 non-stenotic left main arteries using serial IVUS (follow-up 18 +/- 8
      months). Plaques were divided into subgroups according to the follow-up RI:
      follow-up RI >1 (n = 27) versus follow-up RI < or =1 (n = 19). RESULTS: Lesions
      with a follow-up RI >1 had an increase in lumen despite an increase in plaque
      because of an increase in EEM. Conversely, lesions with a follow-up RI < or =1
      had a reduction in lumen as a result of both a plaque increase and EEM decrease.
      Overall, the follow-up RI correlated directly with changes in lesion site EEM
      (baseline-to-follow-up). Although there was no correlation between the follow-up
      RI and changes in reference EEM area, changes in reference EEM area did correlate
      directly with changes in lesion EEM area. In nearly 90% of lesions with a follow
      up RI >1, there was a previously documented increase in EEM area. Using
      multivariate linear regression analysis, the follow-up RI was dependent on the
      baseline RI, the increase in lesion EEM area, and the decrease in reference EEM
      area. The follow-up RI was not dependent on changes in lesion plaque area.
      CONCLUSIONS: The vast majority of left main lesions with a remodeling index >1
      had evidence of a previous increase in lesion-site EEM area.

PMID- 16580525
TI  - C-reactive protein and the vascular endothelium: implications for plaque
      instability.

PMID- 16580524
TI  - C-reactive protein induces matrix metalloproteinase-1 and -10 in human
      endothelial cells: implications for clinical and subclinical atherosclerosis.
AB  - OBJECTIVES: We examined the effect of C-reactive protein (CRP) on matrix
      metalloproteinase (MMP) and inhibitor expression in endothelial cells and in
      patients with clinical and subclinical atherosclerosis. BACKGROUND: In addition
      to predicting atherosclerotic vascular disease, CRP may directly promote a
      proinflammatory/proatherosclerotic phenotype. METHODS: Human umbilical vein
      endothelial cells (HUVECs) and aortic endothelial cells (HAECs) were incubated in
      the presence or absence of CRP (50 mug/ml). Microarray analysis, real-time
      polymerase chain reaction, immunological and activity assays for MMPs were
      performed. Specific inhibitors of mitogen-activated protein kinase pathway were
      used. The MMP-1 and -10 plasma levels were measured in apparently healthy
      subjects (n = 70). Immunolocalization of CRP, MMP-1, and MMP-10 was performed in
      human mammary arteries and carotid endarterectomy specimens. RESULTS: C-reactive
      protein augmented MMP-1 and -10 messenger ribonucleic acid expression in HUVEC (p
      < 0.05) and HAEC (p < 0.01). C-reactive protein stimulation also increased MMP-1
      and -10 protein in conditioned culture medium (p < 0.001), as well as MMP
      activity (p = 0.001). Specific inhibition of p38 or MEK abolished the CRP
      induction of the MMP-1, whereas MMP-10 induction blockade required the
      simultaneous inhibition of p38 and Jun N-terminal kinase pathways. Subjects with
      CRP values >3 mg/l (n = 37) had increased plasma MMP-1 and -10 (p < 0.05), the
      association being significant after adjustment for confounding variables (p =
      0.04 and p = 0.008, respectively). The MMP-10 levels were elevated in subjects
      with higher carotid intima-media thickness (p = 0.009). Increased CRP and MMP-10
      colocalized in endothelial layer and macrophage-rich areas in advanced
      atherosclerotic plaques. CONCLUSIONS: Increased local and systemic CRP-related
      MMP activation might provide a link between inflammation and plaque
      vulnerability.

PMID- 16580527
TI  - Robotic magnetic navigation for atrial fibrillation ablation.
AB  - OBJECTIVES: We assessed feasibility of magnetic catheter guidance in patients
      with atrial fibrillation (AF) undergoing circumferential pulmonary vein ablation
      (CPVA). BACKGROUND: No data are available on feasibility of remote navigation for
      AF ablation. METHODS: Forty patients underwent CPVA for symptomatic AF using the
      NIOBE II remote magnetic system (Stereotaxis Inc., St. Louis, Missouri). Ablation
      was performed with a 4-mm tip, magnetic catheter (65 degrees C, maximum 50 W, 15
      s). The catheter tip was guided by a uniform magnetic field (0.08-T), and a motor
      drive (Cardiodrive unit, Stereotaxis Inc.). Left atrium maps were created using
      an integrated CARTO RMT system (Stereotaxis Inc.). End point of ablation was
      voltage abatement >90% of bipolar electrogram amplitude. RESULTS: Remote ablation
      was successful in 38 of 40 patients without complications. The median mapping and
      ablation time was 152.5 min (range, 90 to 380 min) but was much longer in the
      first 12 patients (192.5 min vs. 148 min; p = 0.012). Median ablation time was
      49.5 min (range, 17 to 154 min), but it was much shorter in the last 28 patients
      than in the first 12 patients (49 min vs. 70 min; p = 0.021). Patients receiving
      remote ablation had longer procedure times than control patients (p < 0.001) with
      similar mapping time but shorter ablation time on right-sided pulmonary veins.
      Many more mapping points regardless of their location were collected remotely (p
      < 0.001). CONCLUSIONS: Remote magnetic navigation for AF ablation is safe and
      feasible with a short learning curve. Although all procedures were performed by a
      highly experienced operator, remote AF ablation can be performed even by less
      experienced operators.

PMID- 16580526
TI  - Prognostic value of pacing-induced mechanical alternans in patients with mild-to
      moderate idiopathic dilated cardiomyopathy in sinus rhythm.
AB  - OBJECTIVES: The relation between the occurrence of pacing-induced mechanical
      alternans and prognosis in patients with mild-to-moderate idiopathic dilated
      cardiomyopathy (IDCM) in sinus rhythm was investigated prospectively. The
      myocardial expression of genes for Ca2+-handling proteins in such patients was
      also examined. BACKGROUND: Mechanical alternans occurs in some patients with
      severe heart failure, but the relation between the occurrence of mechanical
      alternans and prognosis in patients with IDCM has remained unknown. METHODS: Left
      ventricular (LV) pressure was measured during atrial pacing, and LV
      endomyocardial biopsy specimens were collected in 36 IDCM patients and 8
      controls. Idiopathic dilated cardiomyopathy patients were divided into two groups
      consisting of 22 individuals who did not develop mechanical alternans at heart
      rates up to 140 beats/min (group A) and of 14 individuals who did (group B). The
      patients were followed up for a mean of 3.7 years. RESULTS: There was no
      significant difference in LV ejection fraction or the plasma concentration of
      brain natriuretic peptide between groups A and B. The myocardial abundance of
      ryanodine receptor 2 messenger ribonucleic acid (mRNA) was significantly lower in
      groups A and B than in controls, whereas that of sarcoplasmic reticulum Ca2+
      ATPase mRNA was significantly lower in group B than in group A or controls.
      Stepwise multivariate analysis identified pacing-induced mechanical alternans as
      the strongest predictor of cardiac events. Event-free survival in group A was
      significantly greater than that in group B. CONCLUSIONS: The occurrence of pacing
      induced mechanical alternans is a potentially useful indicator of poor prognosis
      in patients with mild-to-moderate IDCM in sinus rhythm.

PMID- 16580528
TI  - Frequency analysis in different types of paroxysmal atrial fibrillation.
AB  - OBJECTIVES: This study sought to investigate the regional frequency distribution
      from multiple bi-atrial sites in different types of paroxysmal atrial
      fibrillation (AF). BACKGROUND: A previous study showed a left atrium (LA) to
      right atrium (RA) frequency gradient in patients with paroxysmal AF. METHODS:
      Forty-four patients (age = 60 +/- 16, male patients = 27) with paroxysmal AF
      originating from the pulmonary veins (PVs) (n = 31) or superior vena cava (SVC)
      (n = 13) were included. Frequency analysis was performed on the intracardiac
      electrograms (7 s, 1 kHz/channel) recorded from PV, posterior LA, coronary sinus
      (CS), posterolateral RA, and SVC. The largest peak frequency was identified as
      the dominant frequency (DF). RESULTS: In the PV-AF patients, there was a
      frequency gradient from the PV ostium to the LA, RA, and SVC (8.5 +/- 3.3 Hz vs.
      5.9 +/- 1.1 Hz vs. 5.2 +/- 0.85 Hz vs. 5.5 +/- 0.48 Hz, respectively, p < 0.001).
      The highest DFs were mostly located at the arrhythmogenic PV ostium (58%). The
      DFs of the arrhythmogenic PV and PV ostium were significantly higher than those
      of the non-arrhythmogenic PVs and PV ostia (p < 0.05). In the SVC-AF patients,
      there was a frequency gradient from the SVC to the RA, LA, and PV (8.0 +/- 2.4 Hz
      vs. 5.9 +/- 1.1 Hz vs. 5.9 +/- 0.7 Hz vs. 5.8 +/- 0.7 Hz, respectively, p =
      0.001). The highest DFs were mostly located inside the SVC (77%) instead of the
      SVC ostium (as compared with PV-AF patients, p = 0.035). CONCLUSIONS: The
      location of the highest DF depended on the arrhythmogenic PV or SVC. A frequency
      gradient was present between the arrhythmogenic thoracic vein and atrium in all
      patients.

PMID- 16580529
TI  - Highest dominant frequencies in atrial fibrillation: a new target for ablation?

PMID- 16580530
TI  - Multislice computed tomography for detection of patients with aortic valve
      stenosis and quantification of severity.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether multislice computed
      tomography (MSCT) provides a reliable, noninvasive imaging modality for
      identification of patients with degenerative aortic valve stenosis (AS) by
      quantifying the aortic valve area (AVA) in comparison to the accepted diagnostic
      standard transthoracic echocardiography (TTE). BACKGROUND: Management of patients
      with degenerative AS is based on the severity of disease. The severity of AS in
      clinical practice is assessed by TTE and classified as mild, moderate, or severe
      according to the AVA. METHODS: Forty-six patients were examined with contrast
      enhanced, electrocardiogram-gated, 16-row MSCT for the evaluation of the
      diagnostic accuracy. In 30 patients, quantification of the AVA with MSCT was
      compared to TTE using the continuity equation with Doppler velocity-time integral
      for calculation of the AVA. RESULTS: Sensitivity of MSCT for the identification
      of patients with degenerative AS was 100%, and the specificity was 93.7%. Thirty
      of 46 patients had AS determined by TTE. Quantification of AVA by MSCT (mean AVA
      = 0.94 cm2) in patients with AS showed a good correlation to TTE (r = 0.89; p <
      0.001). Bland-Altman plot illustrated good intermodality agreement between the
      two methods (limits of agreement, 0.20; 0.29). CONCLUSIONS: Multislice computed
      tomography may provide an accurate, noninvasive imaging technique for detection
      of patients with AS and quantification of AVA.

PMID- 16580531
TI  - Impact of body mass index on cardiac mortality in patients with known or
      suspected coronary artery disease undergoing myocardial perfusion single-photon
      emission computed tomography.
AB  - OBJECTIVES: The purpose of this study was to assess the relationship between body
      mass index (BMI) and the prognostic value of myocardial perfusion single-photon
      emission computed tomography (MPS). BACKGROUND: The prognostic value of MPS in
      the obese has not been evaluated. METHODS: We studied 4,720 patients with and
      10,019 patients without known coronary artery disease (CAD) who underwent rest Tl
      201/stress Tc-99m sestamibi MPS, including 5,233 gated MPS studies and followed
      up (mean 2.7 to 3.2 years). Patients were categorized as normal weight (BMI 18.5
      to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2), or obese (BMI > or =30.0
      kg/m2). RESULTS: Unadjusted annual rates of cardiac death (CD) rose versus stress
      MPS abnormalities in all weight groups (p < 0.001). Obese or overweight patients
      with or without known CAD who had normal MPS were at low CD risk (<1%/year),
      similar to normal weight patients. In CAD, obese and overweight patients with
      abnormal MPS had lower rates of CD compared with normal weight patients (p <
      0.01). In patients with low ejection fraction (EF) by gated MPS, those with
      normal weight had highest CD rate (p = 0.001). Multivariable models revealed that
      BMI was not a predictor of CD in suspected CAD patients (hazard ratio [HR] 0.99;
      95% confidence interval [CI] 0.95 to 1.02) but was an independent inverse
      predictor of CD in known CAD patients (HR 0.95; 95% CI 0.92 to 0.98), especially
      in women, adenosine stress, low EF, or abnormal perfusion. CONCLUSIONS: Normal
      MPS was associated with low risk of CD in patients of all weight categories. In
      patients with known CAD undergoing MPS, obese and overweight patients were at
      lower risk of CD over three years than normal weight patients.

PMID- 16580532
TI  - Prognosis of negative adenosine stress magnetic resonance in patients presenting
      to an emergency department with chest pain.
AB  - OBJECTIVES: This study was designed to determine the diagnostic value of
      adenosine cardiac magnetic resonance (CMR) in troponin-negative patients with
      chest pain. BACKGROUND: We hypothesized that adenosine CMR could determine which
      troponin-negative patients with chest pain in an emergency department have
      coronary artery disease (CAD) or future adverse cardiac events. METHODS:
      Adenosine stress CMR was performed on 135 patients who presented to the emergency
      department with chest pain and had acute myocardial infarction (MI) excluded by
      troponin-I. The main study outcome was detecting any evidence of significant CAD.
      Patients were contacted at one year to determine the incidence of significant CAD
      defined as coronary artery stenosis >50% on angiography, abnormal correlative
      stress test, new MI, or death. RESULTS: Adenosine perfusion abnormalities had
      100% sensitivity and 93% specificity as the single most accurate component of the
      CMR examination. Both cardiac risk factors and CMR were significant in Kaplan
      Meier analysis (log-rank test, p = 0.0006 and p < 0.0001, respectively). However,
      an abnormal CMR added significant prognostic value in predicting future diagnosis
      of CAD, MI, or death over clinical risk factors. In receiver operator curve
      analysis, adenosine CMR was a more accurate predictor than cardiac risk factors
      (p < 0.002). CONCLUSIONS: In patients with chest pain who had MI excluded by
      troponin-I and non-diagnostic electrocardiograms, an adenosine CMR examination
      predicted with high sensitivity and specificity which patients had significant
      CAD during one-year follow-up. Furthermore, no patients with a normal adenosine
      CMR study had a subsequent diagnosis of CAD or an adverse outcome.

PMID- 16580533
TI  - Obstructive sleep apnea syndrome: more insights on structural and functional
      cardiac alterations, and the effects of treatment with continuous positive airway
      pressure.
AB  - OBJECTIVES: We studied structural and functional cardiac alterations in
      obstructive sleep apnea (OSA), their relationship to the severity of OSA, and the
      effects of treatment with continuous positive airway pressure (CPAP). BACKGROUND:
      Obstructive sleep apnea may influence the cardiac function by several mechanisms
      in the awake patient. METHODS: Left and right ventricular morphology and function
      were studied using echocardiography before and after treatment with CPAP in
      symptomatic patients (Epworth sleepiness score, 10 +/- 4.8) with severe OSA
      (apnea-hypopnea index [AHI], 42 +/- 24). The patients (n = 43, 32 men) had no
      known cardiac disease and were obese (body mass index, 31.6 +/- 5.4 kg/m2). The
      same echocardiographic parameters were studied in age-matched overweight patients
      (n = 40; body mass index, 26.4 +/- 2.3 kg/m2). RESULTS: The patients were
      hypertensive (systolic blood pressure, 153 +/- 25 mm Hg), with a higher resting
      heart rate (77 +/- 10 beats/min, p = 0.008) compared with age-matched control
      patients (n = 40). There was right ventricular dilatation, hypertrophic
      interventricular septum, reduced left ventricular stroke volume, tissue Doppler
      determined systolic and diastolic velocities of the left and right ventricle, and
      normal pulmonary artery pressure. The structural and functional parameters were
      significantly associated with AHI (p < 0.004). Multiple stepwise regression
      showed the interventricular septum thickness, right ventricular free wall, and
      mitral annulus tissue Doppler systolic velocities to be predictive of a higher
      AHI (p < 0.001). Six months after treatment with CPAP, significant improvements
      were observed in the symptoms and hemodynamics, as well as left and right
      ventricular morphology and function. CONCLUSIONS: The structural and functional
      consequences of OSA on the heart are influenced by the severity of AHI. These
      effects are reversible if the apneic episodes are abolished.

PMID- 16580534
TI  - Effects of normal aging on left ventricular lusitropic, inotropic, and
      chronotropic responses to dobutamine.
AB  - OBJECTIVES: The purpose of this study was to characterize how aging impacts the
      left ventricular (LV) functional reserve. BACKGROUND: Early diastolic LV filling
      slows markedly with advancing age, but the effects of beta-adrenergic stimulation
      on filling, and its major determinant, relaxation, have not been investigated in
      an aging population. Although the responses of contractility and heart rate to
      catecholamines reportedly diminish with age, the effect of age on the responses
      to steady-state dobutamine infusions is unclear. METHODS: Groups of younger (40
      +/- 10 years, n = 26) and older (68 +/- 11 years, n = 24) normal adult patients
      were studied at baseline and at three progressive dobutamine infusion dosages (5,
      10, and 20 mug/kg/min). The LV function was evaluated by two-dimensional and
      Doppler echocardiography. Myocardial relaxation was evaluated from cardiovascular
      magnetic resonance (CMR)-based rho, a preload-independent surrogate for tau .
      Effective LV pump-function index (PFi), defined as systolic blood pressure/end
      systolic LV diameter, was measured. RESULTS: Both groups showed expected dose
      dependent increases in heart rate and LV systolic function, diastolic function,
      and relaxation. Early LV filling reserve was much greater in younger than older
      patients (E-wave increase from baseline to highest dose, 24.0 vs. 9.5 cm/s, p <
      0.004), although the dose responses of rho were indistinguishable (0.18% vs.
      0.19%/ms, p = 0.22). Whereas dobutamine caused a significantly greater increase
      of PFi in younger than older patients (30.1 vs. 15.6 mm Hg/cm, p < 0.0001), there
      was no difference in heart rate augmentation (37 vs. 38 beats/min, p = 0.94).
      CONCLUSIONS: Aging is accompanied by a blunted inotropic but preserved
      chronotropic response to steady-state dobutamine infusion. Although LV filling
      reserve declines with age, relaxation reserve does not.

PMID- 16580535
TI  - Independent factors associated with mortality, reintervention, and achievement of
      complete repair in children with pulmonary atresia with ventricular septal
      defect.
AB  - OBJECTIVES: We described morphologic characteristics, particularly pulmonary
      anatomy, and determined the prevalence of definitive end states and their
      determinants in children with pulmonary atresia associated with ventricular
      septal defect (PAVSD). BACKGROUND: Pulmonary atresia associated with ventricular
      septal defect represents a broad morphologic spectrum that greatly influences
      management and outcomes. METHODS: From 1975 to 2004, 220 children with PAVSD
      presented to our institution. Blinded angiographic review (n = 171) characterized
      bronchopulmonary segment arterial supply. RESULTS: A total of 185 patients
      underwent surgery, and repair was definitive in 75%. Initial operations included
      systemic-pulmonary artery shunt in 57%, complete primary repair in 31%, or right
      ventricular outflow tract reconstruction in 12%. Based on angiographic review,
      118 patients had simple PAVSD and 53 patients had PAVSD with major aortopulmonary
      collateral arteries (MAPCAs). Overall survival from initial operation was 71% at
      10 years. Risk factors for death after initial operation included younger age at
      repair, earlier birth cohort, fewer bronchopulmonary segments supplied by native
      pulmonary arteries, and initial placement of a systemic-pulmonary artery shunt.
      Competing-risks analysis for initially palliated patients predicted that after 10
      years, 68% achieved complete repair (with associated factors including later
      birth cohort and more bronchopulmonary segments supplied by native pulmonary
      arteries), 22% died without repair, and 10% remained alive without repair.
      Reoperations after complete repair occurred in 38 children (27%), with risk
      factors including older age at palliation, MAPCAs, and more segments supplied by
      collaterals. CONCLUSIONS: Outcomes in children with PAVSD have improved over
      time, and are better in completely repaired cases. Bronchopulmonary arterial
      supply is an important determinant of mortality, achievement of definitive
      repair, and post-repair reoperation.

PMID- 16580536
TI  - Covered Cheatham-platinum stents for aortic coarctation: early and intermediate
      term results.
AB  - OBJECTIVES: This study sought to evaluate the use of covered Cheatham-platinum
      (CP) stents in the treatment of aortic coarctation (CoA). BACKGROUND: Aortic
      aneurysms and stent fractures have been encountered after surgical and
      transcatheter treatment for CoA. Covered stents have previously been used in the
      treatment of abdominal and thoracic aneurysms in adults. We implanted covered CP
      stents as a rescue treatment in patients with CoA aneurysms or previous stent
      related complications and in patients at risk of developing complications because
      of complex CoA anatomy or advanced age. METHODS: Thirty-three covered CP stents
      were implanted in 30 patients; 16 patients had had previous procedures. The
      remaining patients had complex or near-atretic CoA. RESULTS: The mean patient age
      and weight were 28 (+/-17.5) years (range 8 to 65 years), and 62 (+/-13) kg
      (range 28 to 86 kg), respectively. The systolic gradient across the CoA decreased
      from a mean (+/-SD) of 36 +/- 20 mm Hg before to a mean of 4 +/- 4 mm Hg after
      the procedure (p < 0.0001), and the diameter of the CoA increased from 6.4 +/-
      3.8 mm to 17.1 +/- 3.1 mm (p < 0.0001). The follow-up period was up to 40 months
      (mean, 11 months). All stents were patent and in good position on computed
      tomography or magnetic resonance imaging performed three to six months later. In
      43% of the patients antihypertensive medication was either decreased or stopped.
      CONCLUSIONS: Covered CP stents may be used as the therapy of choice in patients
      with complications after CoA repairs, whereas they provide a safe alternative to
      conventional stenting in patients with severe and complex CoA lesions or advanced
      age.

PMID- 16580537
TI  - Microvascular permeabilization and cardiomyocyte injury provoked by myocardial
      contrast echocardiography in a canine model.
AB  - OBJECTIVES: The aim of this research was to evaluate the potential for myocardial
      contrast echocardiography (MCE) to provoke microscale bioeffects in a canine
      model. BACKGROUND: Myocardial contrast echocardiography induces bioeffects in rat
      hearts, but translation of such results to larger animal models is uncertain.
      METHODS: Dogs were anesthetized and prepared for open- (n = 22) or closed- (n =
      6) chest MCE. Evans blue dye was injected intravenously as an indicator of
      microvascular leakage, and propidium iodide was used to stain for irreversibly
      injured myocytes in frozen sections. The contrast agent (Definity, Bristol-Myers
      Squibb Medical Imaging Inc., North Billerica, Massachusetts) was diluted in
      saline and infused intravenously at 2 microl/kg/min. Myocardial contrast
      echocardiography in a short-axis (open-chest) or modified four-chamber view
      (closed-chest) with 1:4 end systolic electrocardiogram triggering was performed
      at 1.5 MHz for 10 min in a single imaging plane. RESULTS: Petechiae and leakage
      of Evans blue were observed in the ultrasound scan plane within the anterior left
      ventricle. For 1.2 MPa and 2.2 MPa, open- or closed-chest MCE, Evans blue content
      in tissue within the scan plane was significantly greater than in tissue outside
      this plane. Counts of propidium-iodide-stained nuclei for 2.2 MPa open-chest MCE
      were also significantly greater inside than outside the scan plane. CONCLUSIONS:
      In a canine model, MCE induces myocardial injury comparable to that seen in the
      rodent model.

PMID- 16580538
TI  - Potential bioeffects of ultrasonic destruction of microbubble contrast agents.

PMID- 16580540
TI  - Highlights of the 2005 scientific sessions of the American Society of Nuclear
      Cardiology: Seattle, Washington, September 29-October 2, 2005.

PMID- 16580541
TI  - President's page: making imaging meaningful.

PMID- 16580539
TI  - Sildenafil improves coronary artery patency in a canine model of platelet
      mediated cyclic coronary occlusion after thrombolysis.
AB  - OBJECTIVES: We sought to assess the effect of sildenafil, a highly-specific type
      5 phosphodiesterase (PDE5) inhibitor, on platelet-mediated cyclic coronary flow
      reductions occurring in a canine model of coronary thrombosis despite aspirin
      therapy. BACKGROUND: The PDE5 inhibitors augment the antithrombotic effects of
      nitric oxide in vitro and in vivo, but it has been proposed that the PDE5
      inhibitor sildenafil is prothrombotic. METHODS: Cyclic coronary flow reductions
      were induced in the left anterior descending coronary artery by creation of a
      stenosis, endothelial injury, and thrombus formation followed by treatment with
      aspirin, heparin, and tissue plasminogen activator. After an initial observation
      period, dogs were treated with or without sildenafil (100 microg/kg bolus
      followed by 4 microg/kg/min infusion). RESULTS: Cyclic coronary flow reductions
      ceased in five of six animals 18 +/- 5 min after initiation of sildenafil but
      continued in all six control animals. The portion of the observation period
      during which the coronary artery was patent increased from 52 +/- 9% to 83 +/- 5%
      after sildenafil administration (p = 0.008) but did not differ between the first
      and second observation periods in untreated dogs (49 +/- 11% vs. 44 +/- 11%,
      respectively). Among animals with plasma free sildenafil levels > or =20 nmol/l,
      cyclic coronary flow reductions were 73 +/- 12% less frequent and the time to
      cessation of cycling 72 +/- 14% shorter than in animals with levels <20 nmol/l (p
      < 0.05 for both). Sildenafil transiently decreased blood pressure 7 +/- 1% but
      did not change heart rate. Sildenafil treatment reduced ex vivo thrombin-induced
      platelet aggregation by 39 +/- 3% (p < 0.005). CONCLUSIONS: Sildenafil improves
      coronary patency in a canine model of platelet-mediated coronary artery
      thrombosis, likely via inhibition of platelet aggregation.

PMID- 16580542
TI  - Modified temporary cardiac pacing using transvenous active fixation leads and
      external re-sterilized pulse generators.

PMID- 16580543
TI  - Brain natriuretic peptide levels in constrictive pericarditis and restrictive
      cardiomyopathy.

PMID- 16580544
TI  - Persistence of neointimal growth 12 months after intervention and occurrence of
      delayed restenosis in patients with left main coronary artery disease treated
      with drug-eluting stents.

PMID- 16580545
TI  - 64-slice peripheral computed tomography angiography: a clinical accuracy
      evaluation.

PMID- 16580546
TI  - Serum plant sterols and atherosclerosis: is there a place for statin-ezetimibe
      combination?

PMID- 16580548
TI  - Complementary medicine has no place in cardiovascular medicine.

PMID- 16580549
TI  - Danshen: a popular chinese cardiac herbal drug.

PMID- 16580552
TI  - Does percutaneous closure of the left atrial appendage prevent stroke in atrial
      fibrillation?

PMID- 16580554
TI  - Introduction to clinical radiation biology.
AB  - The authors have reviewed some of the most important and established factors that
      determine the effectiveness of IR in a wide variety of tumor types and normal
      tissues: the significance of increasing the dose of radiation, the importance of
      altered fractionation schemes, such as accelerated fractionation or
      hyperfractionation, and the need to address tumor hypoxia. Therapeutic gain can
      only be achieved when the increased tumor toxicity produced by these treatment
      modifications is balanced against injury to early-responding as well as late
      responding normal tissues. In the not too distant future, therapeutic gain may be
      maximized by individualized therapies that are based on phenotypic and genotypic
      profiling of tumors and patients. For example, predicting which tumors respond to
      IR with accelerated tumor cell repopulation will allow us to apply more intense
      accelerated treatment regimens, while subjecting patients with slowly
      proliferating tumors to less toxic therapies. Similarly, the combination of
      radiation therapy with molecularly targeted pharmacologic agents will be a highly
      individualized treatment approach. However, to some degree, radiation therapy
      will always have to remain unselective and indiscriminant to inactivate the last
      surviving dormant and probably drug-resistant tumor clonogen. Although the field
      of radiation biology is rapidly evolving as a result of advances in molecular
      biology and genetics and the availability of new technologies, a thorough
      understanding of the established factors that determine radiation responses will
      remain an important prerequisite for the successful application of multimodal
      cancer therapies and molecularly targeted approaches in the future.

PMID- 16580555
TI  - Therapeutic radiation physics primer.
AB  - Therapeutic radiological physics is the branch of physics as applied to radiation
      therapy. Therapeutic radiological physics involves the understanding of the
      radiation sources, types, and characteristics of radiation, interaction of
      radiation with matter, and thereafter the deposition of energy in matter. In
      clinical practice, therapeutic radiological physics deals with the technical
      tasks of preparing a patient to undergo radiation therapy. These tasks include
      simulation, patient data acquisition, individualized planning, verification, and
      dose delivery. The role of a therapeutic radiological physicist is to manage the
      technical aspects of patient care: providing technical expertise to the
      development of the institution, recommending and introducing new treatment
      techniques, and ensuring that all patients undergoing radiation therapy receive
      the best standard of care.

PMID- 16580556
TI  - Modern radiation treatment planning and delivery--from Rontgen to real time.
AB  - The field of radiation oncology has advanced exponentially since the discovery of
      X-rays just over 100 years ago. With the advent of three-dimensional treatment
      planning, the therapeutic index was increased by dose escalation and more
      accurate shielding of normal tissues. Now, even greater advances are under way
      with IMRT, image-guided radiation therapy, delineation and control of organ
      motion, and real-time imaging. Similarly, the use of particle therapies such as
      protons has the potential to effect even more accurate dose distributions.
      Clinical studies investigating these modalities will likely further increase the
      efficacy of radiation in years to come.

PMID- 16580557
TI  - Intensity-modulated radiation therapy and image-guided radiation therapy: small
      clinic implementation.
AB  - In a small clinic with a small patient base, the implementation of IMRT/IGRT
      should be slow, measured, and meticulous. Most radiation oncologists in the
      United States have had no formal training in IMRT/IGRT because the modalities are
      so new. Proper patient selection and a team effort among the clinician,
      physicist, dosimetrist, and therapist are thus all the more critical. The
      clinician in the small clinic can take comfort in remembering that the
      technologies are new, but the principles of good radiation medicine are not. With
      patient selection, a team approach, and publication of data and maturation of the
      literature, IMRT/IGRT will become the new standard of care in academic centers,
      large private clinics, and small clinics alike.

PMID- 16580558
TI  - Stereotactic radiosurgery and stereotactic body radiation therapy: an overview of
      technical considerations and clinical applications.
AB  - SRS and SBRT have emerged as effective local treatment techniques for cranial and
      extracranial tumors, respectively. Clinical indications for SRS and SBRTcontinue
      to be redefined through ongoing clinical investigations. It will be especially
      interesting to investigate how SRS and SBRT might best be combined with new
      molecularly targeted systemic agents as the field of oncology progresses through
      the twenty-first century.

PMID- 16580559
TI  - The emergence of advanced brachytherapy techniques for common malignancies.
AB  - The recent advent and integration of sophisticated radiation planning and imaging
      modalities has improved the quality of brachytherapy treatments, allowing for
      more conformal radiation delivery. Further investigation and follow-up are
      necessary to demonstrate improvements in outcome and morbidity with these refined
      approaches.

PMID- 16580560
TI  - Radiation modifiers: treatment overview and future investigations.
AB  - Many radiosensitizers are in current clinical use. In addition, a myriad of
      potential new targeted therapies, which may also interact with radiation, are in
      clinical development. The clinical utility of new targeted therapies, in
      combination with existing radiation sensitizers (chemotherapies) requires further
      evaluation, as does the understanding of their acute and late radiation effects.
      Free radical scavengers appear to show promise as radioprotectors, but data for
      mucoprotection are less convincing.

PMID- 16580561
TI  - The effect of radiation therapy on normal tissue function.
AB  - As more patients are treated for their primary malignancy with cure or increased
      disease-free intervals, injury to normal tissues will become more detectable and
      an important endpoint for study. Future protocols will probably be modified based
      on toxicity endpoints. In Hodgkin's disease, current protocols use response-based
      treatment strategies to limit therapy. The objective is to provide the same level
      of tumor control and follow normal tissue endpoints for outcome analysis. DVH
      analysis has improved the ability to analyze endpoint data for normal tissues.
      These image-guided platforms will provide the infrastructure needed to continue
      efforts in improving the delivery of radiation therapy.

PMID- 16580562
TI  - Quality-of-life outcomes in oncology.
AB  - QOL outcomes have become an integral component of many clinical oncology trials.
      Much work has been performed testing the validity and reliability of Q OL
      instruments. The current challenge is to understand better the clinical relevance
      of QOL research in oncology. QOL studies should focus on phase III trials with
      clear hypotheses that can lead to clinically meaningful interventions.

PMID- 16580563
TI  - Palliation and supportive care in radiation medicine.
AB  - The treatment of bone metastases represents a paradigm for evaluating palliative
      care in terms of symptom relief, toxicities of therapy, and the financial burden
      to the patient, caregivers, and society. Despite enormous expenditures to treat
      metastases, patients continue to sustain symptoms of the disease, and
      uninterrupted aggressive therapies are pursued until death that incur toxicity in
      approximately 25% of patients. This approach is inconsistent with the goals of
      palliative care, which should efficiently provide comfort using antineoplastic
      therapies or supportive care approaches to the patient with the fewest treatment
      related side effects, recognizing that the patient will die of the disease.The
      development of therapies such as bisphosphonates is important in advancing
      options for palliative care; however, clinical trials demonstrating the efficacy
      of bisphosphonates have not addressed important issues for clinical practice. The
      primary study endpoints should primarily address pertinent patient outcomes such
      as pain relief rather than asymptomatic radiographic findings. These studies
      should define clear indications of when to start and stop the therapy, the
      appropriate patient populations to receive the therapy, and the cost
      effectiveness of the treatment relative to other available therapies such as
      radiation. Cost-utility analyses, which account for a broader domain of cost
      effectiveness, need to be performed as part of clinical trials, especially for
      palliative care endpoints. Clinical trials that include these criteria are
      critical to future practice guideline development. As health care resources
      continue to become more limited, the criteria for care must be better defined to
      avoid administration of therapy with limited benefit. Leadership must come from
      the specialty as clinical trials and clinical practice increasingly interface
      with health care policy. Goals of therapy must remain clear for the benefit of
      the individual and all patients.

PMID- 16580564
TI  - Primer on integrative oncology.
AB  - At the present time, there is no obvious answer for many of these design
      difficulties. This problem will continue to constrain ability to determine the
      efficacy of integrative medical techniques for patients who have cancer.
      Patients, however, will continue to gravitate toward alternative treatments,
      especially when standard cancer treatments fail. Therefore oncologists must be
      aware of alternative medical agents and techniques, and be able to guide their
      patients, rather than simply being dismissive.

PMID- 16580565
TI  - HindIII(+/-) polymorphism of the Y chromosome, blood pressure, and serum lipids:
      no evidence of association in three white populations.
AB  - BACKGROUND: Male sex is associated with elevated levels of cardiovascular risk
      factors, including higher blood pressure (BP). Genetic variants on the Y
      chromosome may contribute to explain the sexual dimorphism in cardiovascular
      diseases. Among them, the HindIII(+/-) polymorphism of the male-specific region
      of the Y chromosome has been associated with BP and serum cholesterol levels,
      with conflicting results. We evaluated the association between the HindIII(+/-)
      polymorphism, prevalence of hypertension, BP, and serum lipid levels in a large
      sample of white men and the previously reported epistatic interaction between
      HindIII(+/-) and the -344C/T polymorphism of the aldosterone synthase gene
      (CYP11B2) on BP. METHODS: From three European populations (UK n = 422; Belgium n
      = 313; Italy n = 1248) 1983 white men were phenotyped for BP and serum lipids and
      genotyped for HindIII(+/-) site and for -344C/T polymorphism in the promoter of
      CYP11B2 by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP). RESULTS: A higher frequency of the HindIII (+) was found in Italians
      (63%) as compared to both British (31%) and Belgians (28%) (P < .0001). We found
      no evidence of association of the HindIII(+/-) site with prevalence of
      hypertension, BP, and serum lipids in any of the three European populations
      examined and in the entire sample. Finally, we did not observe any interaction
      between the HindIII(+/-) polymorphism and the -344C/T variant of CYP11B2 on BP.
      CONCLUSIONS: Our data do not support the hypothesis that the HindIII(+/-) site of
      the Y chromosome is a marker of cardiovascular risk in white men, highlighting
      the need for replication in genetic association studies.

PMID- 16580566
TI  - Prevalence of metabolic syndrome and its relationship to white blood cell count
      in a population of Thai men and women receiving routine health examinations.
AB  - BACKGROUND: Patients with metabolic syndrome (MetS) are at increased risk for
      developing diabetes mellitus and cardiovascular disease. Limited information is
      available about the prevalence of MetS among Thai men and women. In this study we
      sought to estimate the prevalence of MetS among a population of patients
      receiving annual health exams. We also studied the relationship between MetS and
      elevated white blood cell (WBC) count. METHODS: This was a cross-sectional study
      of 1,383 patients (375 men and 1,008 women) who participated in annual health
      examinations at the Preventive Medicine Clinic of the King Chulalongkorn Memorial
      Hospital in Bangkok, Thailand, from July 1999 through February 2000. The presence
      of MetS was defined using the modified criteria of the National Cholesterol
      Education Program Adult Treatment Panel III. RESULTS: Overall, the prevalence of
      the MetS was 12.8% and was more common among men than women (15.7% v 11.7%).
      Advanced age and elevated WBC counts were the only statistically significant risk
      factors of MetS in this population. The WBC count was statistically significantly
      correlated with high-density lipoprotein-cholesterol and triglyceride (P = .05).
      Men with highest WBC count (>or=7.50 x 10(3) cell/microL) had a 2.98-fold
      increased in risk of MetS (odds ratio 2.98, 95% confidence interval 1.29 to
      6.87), as compared with men in the lowest quartile (<5.40 x 10(3) cell/microL).
      Among women, the risk of MetS increased across successive quartiles of WBC counts
      (1.00, 2.26, 2.88, and 4.30, with the lowest quartile as the referent group).
      CONCLUSIONS: In this study of Thai men and women receiving routine health
      examinations, MetS was found to be prevalent. In addition, WBC count (indicative
      of systemic chronic inflammation) is positively associated with MetS.

PMID- 16580567
TI  - Sleep-disordered breathing and blood pressure levels among shift and day workers.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) can be one of the major determinants
      of high blood pressure (BP), but there has been no study on SDB with an emphasis
      on shift workers. The objective of this study was to examine whether a
      relationship between SDB and blood pressure/hypertension is more evident among
      shift workers than among day workers. METHODS: In this cross-sectional study, we
      measured BP levels and oxygen desaturation index (by nocturnal pulse oximetry)
      among 253 male shift workers and 206 male day workers aged 30 to 62 years at
      nuclear power plants in Japan. RESULTS: The prevalence of SDB (3% oxygen
      desaturation index >or=10 and >or=15 per hour) in all subjects was 11.3% (95%
      confidence interval [95% CI] 8.4-14.2) and 6.1% (95% CI 3.9-8.3), respectively,
      with no statistical difference between shift and day workers. Systolic and
      diastolic BP levels were correlated with 3% oxygen desaturation index in all
      subjects after adjustment for potential confounding variables. This association
      was primarily observed among workers aged >or=40 years, more specifically older
      shift workers. CONCLUSIONS: A correlation between SDB severity and diastolic BP
      levels among shift workers aged >or=40 years suggests the importance of screening
      for SDB among shift workers for BP control.

PMID- 16580569
TI  - Comparison of Dinamap PRO-100 and mercury sphygmomanometer blood pressure
      measurements in a population-based study.
AB  - BACKGROUND: The accuracy of automated oscillometric devices has been questioned.
      In addition the acceptability of these devices for research under the field
      conditions is unclear. METHODS: We compared blood pressure (BP) readings obtained
      using the Dinamap PRO-100 with readings obtained using a standard mercury
      sphygmomanometer in 305 participants aged 48 to 86 years who were enrolled in the
      ongoing Multi-Ethnic Study of Atherosclerosis. The BP was measured three times by
      each device in random order in each participant. RESULTS: Approximately one half
      of the participants were male and 46.6% had hypertension. The Dinamap and mercury
      measurements were well correlated (r = 0.89 for systolic BP and r = 0.81 for
      diastolic BP). Overall the Dinamap underestimated BP: the mean difference
      (Dinamap - mercury sphygmomanometer) was -0.5 mm Hg (P = .36, SD = 9.8 mm Hg) for
      systolic BP and -2.9 mm Hg (P < .001, SD = 6.6 mm Hg) for diastolic BP. However,
      the Dinamap device tended to overestimate systolic BP in participants who were 75
      to 86 years of age, who had a pulse pressure >or=60 mm Hg, or who had stages I to
      III hypertension. On the other hand, the Dinamap underestimated diastolic BP
      among these same subgroups but with a smaller underestimate than for the rest of
      the study sample. CONCLUSIONS: Although the BP measurements obtained by the
      Dinamap PRO-100 tend on average to be slightly lower than those obtained by the
      standard mercury sphygmomanometer in middle-aged and older persons, the
      discrepancies may vary with age, pulse pressure, and BP. Health care providers
      and researchers should know of this variation and should interpret Dinamap
      measured BP with caution.

PMID- 16580570
TI  - Relationship between circulating plasma matrix metalloproteinase-9 (gelatinase-B)
      concentration and aortic root dilatation.
AB  - BACKGROUND: Expression of matrix metalloproteinase (MMP) has been shown in aortic
      dissection and aneurysms indicating increased proteolysis compared with the
      normal aorta. However, its role in the development of aortic root dilatation has
      not been studied. We therefore attempted to determine the relationship between
      aortic root diameter and MMP-9 concentration in a hypertensive population.
      METHODS: The 53 hypertensive patients with (n = 27) and without aortic dilatation
      (n = 26) were included in the study. All participants underwent a complete
      transthoracic echocardiographic examination including aortic root measurement.
      Plasma concentration of MMP-9 were determined by the one-step sandwich enzyme
      immunoassay method and compared in both groups. RESULTS: Baseline demographic
      properties were similar in both groups. No subject had significant valvular
      disorder and wall motion abnormality on echocardiographic evaluation. On
      echocardiographic examination only five patients had bicuspid aortic valve. In
      patients with aortic root dilatation, 21 patients were using an antihypertensive
      agent, whereas in patients without aortic root dilatation, 19 patients were using
      an antihypertensive agent. Plasma MMP-9 level was significantly higher in
      patients with aortic root dilatation than in those without dilatation (2.5 +/-
      1.0 v 1.6 +/- 0.9 ng/mL; P = .003). On correlation analysis, we found a positive
      correlation between aortic diameter and plasma MMM-9 levels (r = 0.43, P = .001).
      CONCLUSIONS: Aortic root dilatation is associated with higher MMP release, which
      may indicate the role of increased collagenolytic and elastolytic activities in
      hypertension-induced aortic root dilatation.

PMID- 16580571
TI  - Early growth response gene-1 expression in vascular smooth muscle cells effects
      of insulin and oxidant stress.
AB  - BACKGROUND: Cardiovascular mortality is increased in individuals with insulin
      resistance, and increased oxidant stress is strongly implicated in atherogenesis.
      Early growth response gene-1 (Egr-1) may be an important link between insulin
      resistance and oxidant stress. In this study we examined the effects of insulin
      and oxidant stress on Egr-1 expression in vascular smooth muscle cells (VSMC),
      and identified mechanisms for these effects on Egr-1. METHODS: Rat VSMC were used
      to obtain time course and dose-response curves for insulin and oxidant stress on
      Egr-1 protein expression. Intracellular signaling pathway inhibitors and
      adenoviral vectors with dominant negative effects on specific signaling pathways
      were used to determine mechanisms for these effects. RESULTS: Insulin and oxidant
      stress each significantly stimulate Egr-1 protein expression. Insulin and oxidant
      stress combined have a greater effect on Egr-1 than either alone. Insulin effects
      are mediated via the ERK1/2 MAP kinase pathway, whereas oxidant stress effects
      may be mediated via the ERK5 and p38 MAP kinase pathways. CONCLUSIONS: We
      demonstrated that insulin and oxidant stress stimulate Egr-1 expression in VSMC.
      Insulin effects are mediated via the ERK1/2 MAP kinase pathway, whereas oxidant
      stress effects may be mediated via the ERK5 and p38 MAP kinase pathways. As
      insulin resistance is characterized by compensatory hyperinsulinemia and
      selective impairment of the PI 3-kinase pathway with intact signaling along the
      ERK1/2 MAP kinase pathway, this may have implications for accelerated
      atherosclerosis in insulin resistance.

PMID- 16580572
TI  - Aldosterone and refractory hypertension: a prospective cohort study.
AB  - BACKGROUND: Resistant hypertension is common in clinical practice. The aim of our
      study was to evaluate inappropriate aldosterone activity in causing resistance to
      antihypertensive therapy. METHODS: Among the patients consecutively evaluated for
      the first time between 1995 and 2001, we selected all those (n = 157) with an
      aldosterone-to-renin ratio (ARR) >or=25 (ng/dL)/(ng/mL/h), and plasma aldosterone
      >or=12 ng/dL. Eight patients with Conn adenoma were excluded from the study.
      Fifty-eight were diagnosed as idiopathic aldosteronism (IHA), the other 91
      patients, who did not meet the criteria for primary aldosteronism, were
      operatively classified as aldosterone-associated hypertension (AAH). As a control
      group, we randomly chose 160 patients with essential hypertension and plasma
      aldosterone <12 ng/dL (EH). Antihypertensive treatment was given in accordance to
      World Health Organization Guidelines (1999). The study end point was blood
      pressure (BP) <140/90 mm Hg. RESULTS: During follow-up (22 +/- 2 months), 24
      (41.4%) patients with IHA, 35 (38.5%) with AAH, and 72 (54.0%) with EH reached
      the end point. According to survival analysis, AAH and IHA patients reached the
      end point in a smaller fraction and in a longer time compared with EH patients,
      with no difference between IHA and AAH. At the end of follow-up, IHA and AAH
      patients had higher diastolic BP than EH patients with no difference between IHA
      and AAH. CONCLUSIONS: Patients with elevated aldosterone plasma levels develop
      resistant hypertension, even in the absence of clinically diagnosed primary
      aldosteronism. Their identification will allow a targeted therapy and a more
      effective BP reduction.

PMID- 16580574
TI  - Calcium and conjugated linoleic acid reduces pregnancy-induced hypertension and
      decreases intracellular calcium in lymphocytes.
AB  - BACKGROUND: The aim of the present study was to determine whether the beneficial
      effect of oral supplementation with calcium and conjugated linoleic acid (CLA) in
      the reduction of the incidence of pregnancy-induced hypertension (PIH) is related
      with changes in plasma levels of prostanoids, renin, angiotensin II, calciotropic
      hormones, and plasma and intracellular ionized free calcium. METHODS: These
      mediators were determined using the blood samples obtained from a randomized,
      double-blind, placebo-controlled trial that included 48 healthy primigravidas
      with a family history of preeclampsia and with diastolic notch, recruited from
      four outpatient clinics from two developing countries. Participants were
      randomized to daily oral doses of elemental calcium and CLA or lactose-starch
      placebo from week 18 to week 22 of gestation until delivery. RESULTS: The
      incidence of PIH was significantly reduced in women receiving the supplement (2
      women [8.3%]) compared with placebo (10 women [41.7%]) (relative risk = 0.20, 95%
      confidence interval 0.05-0.82, P = .01). There were no significant differences in
      the plasma concentrations of ionized calcium, prostaglandin E(2), renin,
      angiotensin II, parathormone,and calcitonine. The concentration of intracellular
      ionized free calcium presented a significant reduction after interventions (92.0
      nmol/L [range 62.5 to 220 nmol/L] v 62.5 nmol/L [range 28 to 200 nmol/L; P = .01)
      in the supplemented group but not in the placebo group. The women who developed
      PIH (n = 12) presented a significant increase in the concentrations of
      intracellular calcium after interventions (120 nmol/L [range 89.2 to 240 nmol/L]
      v 137.5 nmol/L [range 89.2 to 138 nmol/L; P = .02). CONCLUSIONS: Calcium and CLA
      supplementation during pregnancy reduces the incidence of PIH, and decreases the
      intracellular concentration of ionized free calcium in peripheral blood
      lymphocytes.

PMID- 16580575
TI  - A factorial study of combination hypertension treatment with metoprolol succinate
      extended release and felodipine extended release results of the Metoprolol
      Succinate-Felodipine Antihypertension Combination Trial (M-FACT).
AB  - BACKGROUND: Many hypertensive patients require combination therapy to achieve
      target blood pressure (BP). beta-Blockers and dihydropyridine calcium channel
      blockers are effective as monotherapy in hypertensive patients and have
      complementary mechanisms for lowering BP. METHODS: This multicenter, randomized,
      placebo-controlled, unbalanced factorial study included a 4- to 5-week single
      blind placebo, 9-week, double-blind treatment as well as a 2-week double-blind,
      down-titration period. Patients (N = 1092) were randomized to one of 16 treatment
      groups: extended-release (ER) metoprolol succinate (25, 100, or 400 mg), ER
      felodipine (2.5, 10, or 20 mg), ER felodipine/ER metoprolol succinate (2.5/25,
      2.5/100, 2.5/400, 10/25, 10/100, 10/400, 20/25, 20/100, or 20/400 mg), or
      placebo. RESULTS: At baseline, treatment groups were well balanced; mean sitting
      BP was 152.6/99.9 mm Hg. Monotherapy with ER metoprolol succinate induced dose
      related reductions in sitting systolic/diastolic BP (DBP) (mean 8.1/7.7 to
      9.7/11.1 mm Hg) as did ER felodipine (mean 7.7/7.7 to 14.0/11.8) and the
      combinations reflected additive effects (mean 13.8/11.0 to 19.8/15.2). The
      decline in the placebo group was 2.1/4.0 mm Hg. All combinations were more
      effective than their components (P < .05 for all but ER metoprolol succinate
      25/ER felodipine 20). When compared with the highest doses of the individual
      agents (ER metoprolol succinate 400 mg; ER felodipine 20 mg), the low-dose
      combination ER metoprolol succinate 25/ER felodipine 2.5 was approximately as
      effective (differences in DBP <1 mm Hg). The most common adverse events leading
      to discontinuation were peripheral edema (4%), headache (2%), and fatigue (1%).
      Higher rates of peripheral edema and flushing were associated with high-dose ER
      felodipine, either alone or in combination. CONCLUSIONS: The antihypertensive
      effects of ER metoprolol succinate and ER felodipine are dose-related, and when
      given in combination, their BP-lowering effects are additive over a wide dose
      range. Low-dose combination therapy is comparable in effectiveness to high-dose
      monotherapy but is better tolerated.

PMID- 16580576
TI  - Tempol in the dorsomedial hypothalamus attenuates the hypertensive response to
      stress in rabbits.
AB  - BACKGROUND: We have recently shown that microinjection of the superoxide
      dismutase mimetic tempol into the pressor region of the rostral ventrolateral
      medulla attenuates the cardiovascular response to mental (air-jet) stress in
      rabbits. In the present study, we examined the influence of tempol on the blood
      pressure (BP) and heart rate (HR) responses to stress in the key region of the
      hypothalamic defense area, the dorsomedial hypothalamus (DMH). METHODS: New
      Zealand White rabbits were implanted with guide cannulae for microinjection into
      the DMH. After 2 weeks of recovery, the cardiovascular response to air-jet stress
      was evaluated before and after bilateral injections of equimolar doses (20 nmol)
      of the superoxide scavengers tempol, tiron, or 3-carbamoyl proxyl (3-CP).
      RESULTS: Microinjection of superoxide scavengers into the DMH did not alter
      resting BP or HR. Air-jet stress evoked a sustained increase in BP (+16 +/- 2 mm
      Hg) and HR (+48 +/- 5 beats/min). Tempol attenuated the pressor and tachycardic
      responses to air-jet stress by 39% +/- 10% and 37% +/- 8%, respectively (P <
      .05), without altering stress-induced tachypnea. Similarly, tiron selectively
      decreased the BP and HR responses to stress by 33% +/- 8% and 53% +/- 13%,
      respectively (P < .05). Conversely, 3-CP, which is structurally close to tempol
      but has a lower superoxide scavenging activity, did not alter the cardiovascular
      stress response, and neither did vehicle. Microinjection of tempol or tiron just
      outside the DMH had little effect on stress responses. CONCLUSIONS: This study
      provides first published evidence that superoxide in the DMH is important in the
      regulation of acute hypertensive and tachycardic responses to mental stress.

PMID- 16580577
TI  - Primary intracerebral hemorrhage during asleep period.
AB  - BACKGROUND: The onset of intracerebral hemorrhage (ICH) has a circadian
      variation, with a lower risk during the asleep period. It is unclear, however,
      whether ICH during the asleep period differs from that during the awake period in
      pathophysiologic nature. The purpose of this study is to elucidate the incidences
      and clinical features of ICH during the asleep period. METHODS: We studied 129
      consecutive patients with primary ICH and classified them into two groups
      according to the circumstance of their stroke onset, either during the awake
      period (awake ICH group) or the asleep period (asleep ICH group). Demographic and
      clinical characteristics were then compared between the two groups. RESULTS: Of
      the patients, 19 (14.7%) had ICH during the asleep period. The mortality rate at
      1 month after the stroke was significantly higher in the asleep ICH group than in
      the awake ICH group (21.1% v 4.9%, P = .0325). The hemorrhage volume in the
      asleep ICH group was also significantly larger than that in the awake ICH group
      (mean volume, 32.6 mL v 16.7 mL, P = .0122). CONCLUSIONS: Our findings indicate
      that ICH during the asleep period may be more detrimental compared with ICH
      during the awake period, causing larger hematoma and higher mortality rates.

PMID- 16580578
TI  - Modulation of cardiac and aortic peroxisome proliferator-activated receptor-gamma
      expression by oxidative stress in chronically glucose-fed rats.
AB  - BACKGROUND: The aim of the present study was to examine the chronic effects of
      alpha-lipoic acid on proliferator peroxisome activated receptors-gamma (PPAR
      gamma) and PPAR-alpha expressions in cardiovascular tissues of chronically
      hypertensive insulinoresistant rats. We have also evaluated the chronic effects
      of high levels of insulin, glucose, or both on superoxide anion (O(2)(-))
      production in aortic smooth muscle cells (SMCs) in the presence or in absence of
      pioglitazone, a PPAR-gamma agonist. METHODS: The PPAR-gamma and PPAR-alpha
      expressions were measured by Western blot. The oxidative stress was evaluated by
      measuring the O(2)(-) production using the lucigenin method. RESULTS: Increases
      in blood pressure, in aortic O(2)(-) production, in glucose or insulin levels,
      and in insulin resistance, as well as the decrease in PPAR-gamma protein levels
      in aorta and heart tissues were prevented or attenuated in glucose-treated rats
      fed with lipoic acid. Chronic treatment with pioglitazone prevented the marked
      increase in O(2)(-) production in cultured SMCs chronically treated with high
      insulin combined or not with high glucose levels. CONCLUSIONS: The combined
      therapy with the antioxidant alpha-lipoic acid restored PPAR-gamma levels in
      cardiovascular tissues and attenuated or prevented the development of insulin
      resistance and hypertension in chronically glucose-fed rats. Moreover, the
      finding that pioglitazone was also efficient in preventing the increase in
      oxidative stress in SMCs treated with high insulin combined with high glucose
      concentrations supports the hypothesis that the activation of PPAR-gamma activity
      can counteract the oxidative stress that seems to be implicated in the
      development of hypertension and insulin resistance.

PMID- 16580579
TI  - Apocynin but not L-arginine prevents and reverses dexamethasone-induced
      hypertension in the rat.
AB  - BACKGROUND: Dexamethasone (Dex)-hypertension in rats is associated with increased
      oxidative stress. We investigated effects of the NAD(P)H oxidase inhibitor
      apocynin and the nitric oxide (NO) precursor L-arginine on Dex-hypertension to
      determine the relative roles of NAD(P)H oxidase and uncoupling in the reactive
      oxygen species (ROS) generation and hypertension. METHODS: Male Sprague-Dawley
      rats (n = 10/group) received Dex (20 microg/kg/day subcutaneously) or saline
      (vehicle) for 14 days. In a prevention study, rats received 4 days of apocynin
      treatement (1.5 mmol/L in drinking water) followed by Dex/saline for 12 days. In
      reversal studies, apocynin or L-arginine was given from day 8 to 14. Systolic
      blood pressure (SBP) was measured by tail cuff, and thymus weight was used as a
      marker of glucocorticoid activity. RESULTS: Administration of Dex increased SBP
      (104 +/- 3 to 122 +/- 3 mm Hg, P < .01, mean +/- SEM) and decreased thymus and
      body weight (P' < .05). Apocynin alone had no effect on SBP, BW, or thymus
      weight. Apocynin prevented (122 +/- 4 Dex, 111 +/- 3 mm Hg Apocynin+Dex, P' <
      .05) and reversed Dex-hypertension (130 +/- 4 to 116 +/- 4 mm Hg, P < .01). L
      arginine did not reverse Dex-hypertension. CONCLUSIONS: In male SD rats, apocynin
      but not l-arginine prevented and reversed Dex-hypertension, suggesting that
      NAD(P)H oxidase-mediated superoxide production but not endothelial nitric oxide
      synthase uncoupling is important in Dex-hypertension.

PMID- 16580580
TI  - Carvedilol action is dependent on endogenous production of nitric oxide.
AB  - BACKGROUND: Carvedilol is known to be an adrenoreceptor blocker and free radical
      scavenger, used in hypertension and cardiac failure. However, its therapeutic
      actions cannot be fully explained by these mechanisms. In these studies, we
      tested the hypothesis that carvedilol action is associated with the
      synthesis/release of nitric oxide (NO). METHODS: Male Wistar rats (n = 22), 9
      weeks old, were anesthetized with an intraperitoneal injection of sodium
      pentobarbital. Mean arterial pressure and arterial NO levels were monitored
      throughout the experiments. Carvedilol (1 mg/kg, intravenously [iv]) effects were
      evaluated before and after NO synthase (NOS) inhibitor N(omega)-nitro-L-arginine
      methyl ester (L-NAME, 5 mg/kg, iv). RESULTS: Carvedilol induced a significant
      decrease in basal arterial pressure (from 126.6 +/- 4.3 mm Hg to 75.9 +/- 3.0 mm
      Hg, P < .001) and significant increase in NO levels (from 17.9 +/- 1.7 micromol/L
      to 32.2 +/- 2.5 micromol/L, P < .001). After administration of L-NAME the
      arterial pressure increased (129.9 +/- 5.0 mm Hg, P < .001) with concomitant
      decrease in NO levels (13.4 +/- 1.6 micromol/L, P < .01). The second carvedilol
      administration (post-L-NAME) did not affect either arterial pressure (108.3 +/-
      8.0 mm Hg) or NO levels (22.1 +/- 1.3 micromol/L). CONCLUSIONS: Our results
      suggest that the carvedilol-induced decrease of blood pressure is associated with
      an increase of plasma NO levels. Furthermore, NOS inhibition results in
      impairment of carvedilol hemodynamic effects and plasma NO levels. Therefore,
      these results are consistent with the hypothesis that the hemodynamic effect of
      carvedilol is in part dependent on endogenous NO production.

PMID- 16580581
TI  - Metabolic risk factors and markers of cardiovascular and renal damage in
      overweight subjects.
AB  - BACKGROUND: The prevalence of overweight and obesity in the United States has
      dramatically increased. Obesity clusters with a variety of hemodynamic and
      metabolic disturbances that increase the risk of cardiovascular disease. In this
      study we evaluated whether overweight subjects with hypertension also manifest
      hemodynamic and metabolic abnormalities compared with individuals of normal
      weight. METHODS: In a cohort of 129 patients with essential hypertension we
      measured the relationship between body mass index (BMI), blood pressure (BP),
      insulin sensitivity, lipid profile, and markers of organ damage including
      thickness of the carotid artery (IMT) and urine albumin excretion (UAE). A total
      of 41 normotensive, age-matched, healthy individuals served as control subjects.
      RESULTS: Hypertensive individuals showed higher levels of serum triglycerides,
      insulin area-under-the-curve (AUC), UAE, and greater IMT than normotensive
      subjects. Overweight hypertensive subjects showed higher levels of serum
      triglycerides, LDL cholesterol, glucose AUC, insulin AUC, UAE, and IMT than
      hypertensive subjects with normal body weight (BMI <25). Night-time systolic BP
      was higher and night-time fall in BP was lower among overweight than among normal
      weight hypertensive patients. Simple regression analysis showed that BMI was
      correlated with age, UAE, BP, insulin and glucose AUC, serum triglycerides,
      cholesterol, and IMT in hypertensive subjects. However multiple regression
      analyses showed that BMI significantly correlated only with UAE. CONCLUSIONS: The
      study results show that increased body weight clusters with a variety of
      hemodynamic and metabolic abnormalities in hypertensive subjects. However
      multiple regression analyses showed a significant correlation only between BMI
      and UAE, a marker and predictor of cardiovascular and renal disease.

PMID- 16580582
TI  - Assessing cell K physiology in hypertensive patients. A new clinical and
      methodologic approach.
AB  - The assessment of potassium (K) effects in hypertension involves a history of
      complex research in cell K function and body K homeostasis. These studies provide
      evidence for the role of K ions in vascular and renal function, insulin
      resistance, glucose uptake, and the renin-angiotensin-aldosterone system; and
      there have been an impressive number of clinical and epidemiologic research
      relating dietary intake K and regulation of blood pressure. However, the usual
      technique by which K metabolism is assessed in clinical practice (plasma or serum
      K) provides no useful data for estimating disorders in cell K transport that
      occurs in hypertensive patients or that may follow the administration of
      diuretics, beta-blockers, or nonsteroidal anti-inflammatory drugs. This fact
      becomes more crucial if associated with the physiologic decline in body K stores
      occurring after the age of 30 years, which may impair the long-term treatment of
      hypertensive individuals. In this context, this article presents a review of the
      clinical and research methods that can be used to assess more accurately K
      metabolism and cell K physiology in hypertensive patients, including a heritable
      defect in red blood cell K transport.

PMID- 16580583
TI  - Latent autoimmune diabetes of adults (LADA).

PMID- 16580584
TI  - Assessment of physical activity in an outpatient obesity clinic in southern
      Italy: results from a standardized questionnaire.
AB  - BACKGROUND AND AIM: Sedentary lifestyle contributes to increased body weight in
      western societies. We evaluated physical activity (PA) and its association with
      some clinical and biochemical parameters in overweight and obese outpatients.
      METHODS AND RESULTS: Two hundred and seventy-eight overweight obese outpatients,
      aged 18-65 years, were recruited in this cross-sectional study. Patients were
      interviewed about their usual PA, using a standardized questionnaire. A total
      metabolic index (TMI) was derived estimating weekly energy expenditure. In Class
      III obese patients, fasting serum HDL-cholesterol (HDL-Chol) and resting heart
      rate (HR) were also measured. BMI was inversely related to TMI in the whole group
      (r = -0.123, p = 0.041). Dividing the patients into groups 1 and 2 according to
      median BMI (30.3 kg/m(2)), group 1 had a significantly higher TMI than group 2 (p
      = 0.003), mainly due to the difference in weekly walking time (p < 0.001). Among
      Class III obese patients, despite similar BMI, the group with longer walking time
      had both significantly higher HDL-cholesterol (p = 0.046) and lower HR (p <
      0.001). CONCLUSION: In overweight and obese individuals BMI is inversely related
      to PA energy expenditure. This relationship can be, at least in part, ascribed to
      the reduction of weekly walking time with increasing BMI. In Class III obese
      patients, even a low level of PA can positively affect both HDL-Chol and resting
      HR. It appears useful to focus on obese patients in also in general practice in
      order to recognize sedentary life styles and encourage PA through individualized
      programs.

PMID- 16580585
TI  - In vivo antiatherogenic properties of olive oil and its constituent lipid classes
      in hyperlipidemic rabbits.
AB  - BACKGROUND AND AIM: The consumption of olive oil has been associated with lower
      incidence of cardiovascular disease in the Mediterranean countries. This may be
      due in part to the action of platelet-activating factor (PAF) antagonists which
      we have previously demonstrated to be present in olive oil. In order to assess
      the in vivo effects of olive oil lipids and PAF in the development of
      atherosclerosis, the effects of diet supplementation with olive oil (OO), olive
      oil polar lipid extract (OOPLE) and olive oil neutral lipid extract (OONLE) were
      studied in rabbits fed a cholesterol-enriched diet. METHODS AND RESULTS: Rabbits
      were fed for 45 days with atherogenic diet (Group A) supplemented with OO (Group
      B), OOPLE (Group C) or OONLE (Group D). Lipoprotein profiles, plasma in vitro
      oxidation, blood PAF levels, PAF-induced platelet aggregation and PAF
      acetylhydrolase (PAF-AH) activity, were measured on day 0 and 45. Atherosclerotic
      lesions formed in the aortic wall and wall elasticity were assessed on day 45.
      Changes in lipid profile were in accordance with previous studies. Blood PAF
      levels were higher in group A and decreased in group D on day 45. In rabbits fed
      an atherogenic diet (Group A) blood PAF and PAF-AH increased, atherosclerotic
      lesions formed and the elasticity of vessel walls declined. In animals fed olive
      oil (Group B) or OOPLE (Group C) blood PAF-AH increased, platelet aggregation was
      attenuated, less oxidation occurred in plasma, lesion thickness was reduced and
      vessel walls retained elasticity. Most of these beneficial changes were not seen
      in animals fed OONLE (Group D) although blood PAF and plasma oxidation were
      lower. CONCLUSIONS: The antiatherogenic effects of OO result from OOPLE. The
      beneficial effect of these factors is linked to PAF metabolism and proaggregant
      activity.

PMID- 16580586
TI  - Associations between dietary pattern and lifestyle, anthropometry and other
      health indicators in the elderly participants of the EPIC-Italy cohort.
AB  - INTRODUCTION: Epidemiological studies have shown that dietary behaviour is an
      important aetiological factor in various chronic diseases. We used principal
      component factor analysis to identify dietary patterns and to examine the
      associations of these patterns with health-related variables in a sample of
      elderly (> or =60 years) Italians participating in the European Prospective
      Investigation into Cancer and Nutrition (EPIC). METHODS AND RESULTS: Exploratory
      factor analysis was applied to the intake of food groups as estimated by semi
      quantitative food questionnaires. Individual participants were assigned factor
      scores, indicating the extent to which their diet conformed to each of the four
      dietary patterns identified: prudent (cooked vegetables, pulses, cabbage, seed
      oil and fish); pasta & meat (pasta, tomato sauce, red meat, processed meat, bread
      and wine); olive oil & salad (raw vegetables, olive oil, soup and chicken); and
      sweet & dairy (sugar, cakes, ice cream, coffee and dairy). Highly educated people
      had high scores on prudent and low scores on pasta & meat. The pasta & meat and
      prudent patterns were strongly positively associated with body mass index (BMI)
      and waist-to-hip ratio (WHR) in men and women. Hyperlipidaemic men and women
      consumed more of the prudent and olive oil & salad patterns and less of the sweet
      & dairy pattern than those with normal lipids. The olive oil & salad was
      significantly higher and the pasta & meat and sweet & dairy patterns
      significantly lower in men and women who had dieted over the previous year,
      suggesting awareness of the health consequences of these patterns. CONCLUSIONS:
      Dietary pattern analysis provides a characterization of recurrent dietary
      behaviour in elderly people, and can be used to provide tangible dietary advice
      to elderly people.

PMID- 16580587
TI  - Effects of pistachio nuts consumption on plasma lipid profile and oxidative
      status in healthy volunteers.
AB  - BACKGROUND AND AIM: Effects of pistachio nuts consumption on plasma lipid profile
      and oxidative status were investigated in healthy volunteers with normal lipid
      levels. METHODS AND RESULTS: The study was conducted in 24 healthy men and 20
      healthy women. All subjects consumed their regular diets during a 1-week period.
      After this period, half of the subjects (12 men and 10 women, mean age 32.8 +/-
      6.7 years) were randomized to a regular diet group and the other half (12 men and
      10 women, mean age 33.4 +/- 7.2 years) were randomized to a pistachio group which
      involved substituting pistachio nuts for 20% of their daily caloric intake for 3
      weeks. Plasma total cholesterol, low-density lipoprotein (LDL), high-density
      lipoprotein (HDL), triglyceride, malondialdehyde (MDA) and antioxidant potential
      (AOP) were measured before and after the dietary modification from all the
      subjects. After 3 weeks, with the pistachio diet, the mean plasma total
      cholesterol, MDA levels and, total cholesterol/HDL and LDL/HDL ratios were found
      to be significantly decreased (P < 0.05, P < 0.05, P < 0.001 and P < 0.01,
      respectively); on the contrary, HDL and AOP levels, and AOP/MDA ratios were
      significantly increased (P < 0.001, P < 0.05 and P < 0.01, respectively).
      Triglyceride and LDL levels also decreased but this was not statistically
      significant (P > 0.05). CONCLUSION: These results indicated that consumption of
      pistachio nuts decreased oxidative stress, and improved total cholesterol and HDL
      levels in healthy volunteers.

PMID- 16580588
TI  - Variations of peripheral markers of serotoninergic system in selected vascular
      patients.
AB  - BACKGROUND AND AIM: Serotonin (5-HT), a decarboxylated derivative of tryptophan,
      is synthesized in the enterochromaffin cells and released into blood stream to be
      incorporated into platelets. At the site of endothelial lesions, platelets
      aggregate and secrete 5-HT that presents several vascular actions involved in
      thrombosis and atherogenesis. In fact, 5-HT may induce vasoconstriction in the
      presence of endothelial injury, aggregation of platelets, and mitogenesis of
      arterial smooth muscle cells and endothelial cells. It may also contribute to the
      vascular inflammation associated with atherogenesis by increasing the synthesis
      of Interleukin-6 in vascular smooth muscle cells. We evaluated serotonin levels
      in plasma and platelets of patients with unstable angina and ischemic stroke, to
      identify an association between serotonin and atherosclerosis of coronary and
      cerebral arteries. METHODS AND RESULTS: Twenty patients (14 men, 6 women, mean
      age 69 +/- 10 years) with unstable angina and 15 patients (7 men, 8 women, mean
      age 81 +/- 10 years) with ischemic stroke were included in the study. Twenty-four
      healthy subjects matched for age and sex constituted the control group. Blood
      samples were drawn in the morning to determine plasma and platelet concentrations
      of serotonin. In patients with unstable angina serotonin levels in platelets were
      significantly lower (p < 0.001) than those observed in controls, while serotonin
      concentrations in plasma did not significantly differ from those found in
      controls. In patients affected by stroke serotonin levels in plasma and in
      platelets did not significantly differ from those found in normal subjects.
      CONCLUSIONS: Our findings may contribute to the knowledge to different mechanisms
      involved in the pathogenesis of cardiac and cerebral ischemia.

PMID- 16580590
TI  - Endothelial dysfunction and oxidative stress in arterial hypertension.
AB  - A large body of evidence indicates that endothelial dysfunction is a
      characteristic of patients with essential hypertension. By definition,
      endothelial dysfunction is a functional and reversible alteration of endothelial
      cells, resulting from impairment in nitric oxide (NO) availability and oxidative
      stress. Superoxide anion is a major determinant of NO biosynthesis and also acts
      as a vasoconstrictor. In addition, NO synthase (NOS) can generate superoxide
      rather than NO in response to atherogenic stimuli ("NOS uncoupling"). Under these
      circumstances, NOS may become a peroxynitrite generator, leading to a dramatic
      increase in oxidative stress, since peroxynitrite has additional detrimental
      effects on vascular function by lipid peroxidation. Increased levels of
      biomarkers of lipid peroxidation and oxidative stress have been found in patients
      with hypertension. In particular, patients with hypertension-related
      microvascular changes showed increased lipid peroxidation and platelet activation
      when compared with patients with absent or early signs of retinopathy.
      Furthermore, oxidant stress has been shown to play an important role in promoting
      a prothrombotic state in the vascular system. For all these reasons, endothelial
      dysfunction is evoked in hypertensive patients as promotor of vascular
      progressive damage and atherosclerotic and thrombotic complications through the
      enhanced oxidative stress of arterial walls. This broadens the cardiovascular
      risk of hypertensive patients and explains the insufficient role of the strict BP
      reduction in the prevention of vascular complications, thus opening up new
      perspectives on the antioxidant properties of currently available
      antihypertensive drugs and supplementation with antioxidant principles.

PMID- 16580592
TI  - Comments on Raspanti and co-workers' paper regarding the 3D structure of crimps
      in the rat Achilles tendon.

PMID- 16580589
TI  - In-vivo metabolism of VLDL-apolipoprotein-B, -CIII and -E in normolipidemic
      subjects.
AB  - BACKGROUND AND AIM: ApoE and apoC-III are important components of lipoprotein
      metabolism. While the function of both apoproteins is relatively well understood,
      little is known about the in vivo metabolism of these proteins, partly because of
      the lack of a standardized method to isolate these apoproteins in large sample
      numbers. METHODS AND RESULTS: We developed a new reverse phase HPLC method
      (acetonitril/phosphate gradient; Aquapore RP-300, 7 microm, 220 x 4.6 mm) to
      isolate a number of different apoproteins, including apoC-III and apoE from VLDL.
      This method was then used in a study which aimed at determining VLDL-apoE-3 and
      VLDL-apoC-III metabolism. In addition VLDL-apoB and LDL-apoB metabolism was
      determined. Endogenous labeling with d(3)-leucine, mass spectrometry and
      multicompartmental modeling was used in 6 normolipidemic healthy male subjects.
      Tracer/tracee ratios of free plasma leucine, VLDL-apoE, -apoC-III, -apoB, and LDL
      apoB leucine were determined over 60 h following a bolus of d(3)-leucine (5 mg
      kg(-1)). In all subjects sufficient apoC-III could be isolated by reverse phase
      HPLC to derive metabolic parameters, while apoE metabolic parameters could only
      be determined if apoE plasma concentration was 0.75 mg dl(-1) or higher. Compared
      to VLDL-apoB (FCR 10.4 +/- 3.3 d(-1), production 17.8 +/- 4.5 mg kg(-1) d(-1)),
      VLDL-apoE-3 (FCR 1.03 +/- 0.11 d(-1), production 0.50 +/- 0.29 mg kg(-1) d(-1))
      and VLDL-apoC-III (FCR 1.67 +/- 1.22 d(-1), production 0.44 +/- 0.24 mg kg(-1) d(
      1)) parameters were much lower. This indicates that apoE-3 and apoC-III
      recirculate in plasma and that only a small fraction of apoE and apoC-III on VLDL
      is newly synthesized. CONCLUSIONS: We conclude that HPLC methodology can be used
      to isolate VLDL-apoC-III and apoE for metabolic studies and that the metabolic
      fate of apoC-III and apoE is different from that of apoB because both apoproteins
      recycle through the VLDL fraction.

PMID- 16580594
TI  - Can single-patient investigational new drug studies hurry slow trains to the fast
      track?
AB  - Tips from an Irish playwright and a Finnish oncologist could help the United
      States' National Cancer Institute reach its 2015 goal.

PMID- 16580595
TI  - Joseph Miletich talks about big Pharma, biotech and the future of Amgen.
      Interview by Steve Carney.

PMID- 16580596
TI  - Keynote review: allosterism in membrane receptors.
AB  - Allosteric modulation of membrane receptors has been intensively studied in the
      past three decades and is now considered to be an important indirect mechanism
      for the control of receptor function. The allosteric site on the GABA(A) receptor
      is the target for the most widely prescribed sleep medicines, the
      benzodiazepines. Cinacalcet, an allosteric enhancer of the calcium-sensing
      receptor, is used to treat secondary hyperparathyroidism. Allosteric ligands
      might be especially valuable to control receptors for which the design of
      selective orthosteric agonists or antagonists has been elusive, such as
      muscarinic acetylcholine receptors.

PMID- 16580597
TI  - Immunomics: discovering new targets for vaccines and therapeutics.
AB  - T-cell-epitope mapping has emerged as one of the most powerful new drug discovery
      tools for a range of biomedical applications. Initially, T-cell-epitope discovery
      was applied to the development of vaccines for infectious diseases and cancer. T
      cell-epitope-mapping applications have now expanded to include reengineering of
      protein therapeutics (a process now called deimmunization), as well as the fields
      of autoimmunity, endocrinology, allergy, transplantation and diagnostics.
      Research employing T-cell-epitope mapping falls within the realm of immunomics, a
      new field that addresses the interface between host and (pathogen) proteome,
      bridging informatics, genomics, proteomics, immunology and clinical medicine.
      This review highlights aspects of recent immunomics research that are related to
      the discovery of the T-cell immunome.

PMID- 16580598
TI  - What makes a good anti-inflammatory drug target?
AB  - This review focuses on the major, 'successful' target families in inflammation
      and attempts to identify some of the key features of what makes a good anti
      inflammatory target. The review is based on a systematic analysis of approved
      anti-inflammatory drugs grouped according to their drug-target family. The
      cytokine family is a drug-dense area. They have yielded and continue to yield a
      rich stream of drugs. As in other therapeutic areas, G-protein-coupled receptors
      (GPCRs), also known as seven-transmembrane pass receptors, have provided
      significant drug targets. In addition, the superfamilies of cell adhesion
      molecules and co-stimulatory molecules, which have special relevance to immune
      processes, have begun to provide the first approved drugs and might yield many
      more. The recent, rapid increase in the number of defined targets in the immune
      system -- leukocyte surface antigens, cytokines, GPCRs, adhesion molecules and co
      stimulatory molecules -- will ensure a rich stream of future anti-inflammatory
      drug targets.

PMID- 16580599
TI  - Host-pathogen systems biology.
AB  - Unlike traditional biological research that focuses on a small set of components,
      systems biology studies the complex interactions between a large number of genes,
      proteins and other elements of biological networks and systems. Host-pathogen
      systems biology examines the interactions between the components of two distinct
      organisms, either a microbial or viral pathogen and its animal host or two
      different microbial species in a community. With the availability of complete
      genomic sequences of various hosts and pathogens, together with breakthroughs in
      proteomics, metabolomics and other experimental areas, the investigation of host
      pathogen systems on a multitude of levels of detail has come within reach.

PMID- 16580600
TI  - The promise of a virtual lab in drug discovery.
AB  - To date, the life sciences 'omics' revolution has not lived up to the expectation
      of boosting the drug discovery process. The major obstacle is dealing with the
      volume and diversity of data generated. An enhanced-science (e-science) approach
      based on remote collaboration, reuse of data and methods, and supported by a
      virtual laboratory (VL) environment promises to get the drug discovery process
      afloat. The creation, use and preservation of information in formalized knowledge
      spaces is essential to the e-science approach. VLs include Grid computation and
      data communication as well as generic and domain-specific tools and methods for
      information management, knowledge extraction and data analysis. Problem-solving
      environments (PSEs) are the domain-specific experimental environments of VLs.
      Thus, VL-PSEs can support virtual organizations, based on the changing
      partnerships characteristic of successful drug discovery enterprises.

PMID- 16580601
TI  - Targeting N-type and T-type calcium channels for the treatment of pain.
AB  - Severe chronic pain afflicts a large number of people worldwide but satisfactory
      relief from such pain is difficult to achieve with drugs that are currently
      available, and so there is a great need for the development of new, efficacious
      and safe analgesics. Voltage-gated calcium-permeable ion channels are multi
      subunit complexes that regulate neuronal excitability, action-potential firing
      patterns and neurotransmission in nociceptive pathways. Although multiple
      subtypes of voltage-gated calcium channels exist, pharmacological and ion-channel
      gene knockdown approaches in animals have revealed N-type and T-type calcium
      channels to be particularly attractive molecular targets for the discovery and
      development of new analgesic drugs. The recent approval of Prialt (Elan
      Pharmaceuticals) provides the ultimate target validation for N-type calcium
      channels, namely proof that they are key regulators of nociceptive signaling in
      humans.

PMID- 16580602
TI  - Dual-action peptides: a new strategy in the treatment of diabetes-associated
      neuropathy.
AB  - Peripheral neuropathy is one of the most common and debilitating complications of
      type 1 and type 2 diabetes mellitus. Recent studies have shown that several
      small, non-neural peptides possess neurotrophic activity and exert beneficial
      effects on nervous system function in experimental and clinical diabetes. Two of
      these, C-peptide and islet neogenesis-associated protein peptide, are derived
      from pancreatic proteins and use related signal transduction mechanisms.
      Derivatives of erythropoietin possess similar properties in the nervous system.
      As a group, these peptides are of increasing interest as leads to potential new
      approaches in the treatment of diabetes-associated neuropathies and other
      neurodegenerative conditions. This review addresses the recent advances made with
      these peptides in the context of diabetic neuropathy, and highlights similarities
      and differences in their mechanisms of action from the perspective of combination
      therapy.

PMID- 16580603
TI  - Structure-based development of target-specific compound libraries.
AB  - The success or failure of a small-molecule drug discovery project ultimately lies
      in the choice of the scaffolds to be screened -- chosen from among the many
      millions of available compounds. Therefore, the methods used to design compound
      screening libraries are key for the development of new drugs that target a wide
      range of diseases. Currently, there is a trend towards the construction of
      receptor-structure-based focused libraries. Recent advances in high-throughput
      computational docking, NMR and crystallography have facilitated the development
      of these libraries. A structure-based target-specific library can save time and
      money by reducing the number of compounds to be experimentally tested, also
      improving the drug discovery success rate by identifying more-potent and specific
      binders.

PMID- 16580604
TI  - Defining and maintaining a high quality screening collection: the GSK experience.
AB  - Understanding the quality of a screening collection is the first step to
      improving it and, as a result, the quality of the screening process. This article
      outlines how this issue was approached at GlaxoSmithKline and some of the hurdles
      that needed to be overcome to achieve success. The article focuses specifically
      on the necessary software and hardware infrastructure needed, and at some of the
      extra benefits of such a project in terms of data mining and data modelling.

PMID- 16580608
TI  - Recent progress in inherited kidney diseases.

PMID- 16580609
TI  - Nephrogenic diabetes insipidus.
AB  - Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is
      characterized by an inability to concentrate urine despite normal or elevated
      plasma concentrations of the antidiuretic hormone arginine vasopressin (AVP).
      Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical
      manifestations of the disease. About 90% of patients with congenital NDI are
      males with X-linked recessive NDI (OMIM 304800) who have mutations in the
      arginine-vasopressin receptor 2 (AVPR2) gene that codes for the vasopressin V2
      receptor. In about 10% of the families studied, congenital NDI has an autosomal
      recessive or autosomal dominant mode of inheritance (OMIM 222000 and 125800). In
      these families, mutations have been identified in the aquaporin-2 gene (AQP2)
      (OMIM 107777), which codes for the vasopressin-sensitive water channel. Most
      missense AVPR2 mutations lead to receptors that are trapped intracellularly; a
      few mutant receptors reach the cell surface but are unable to bind AVP or to
      properly trigger an intracellular cyclic adenosine monophosphate signal.
      Similarly, most AQP2 mutant proteins are also misrouted. Prior knowledge of AVPR2
      or AQP2 mutations in NDI families and perinatal mutation testing is of direct
      clinical value because early diagnosis and treatment can avert the physical and
      mental retardation associated with repeated episodes of dehydration.

PMID- 16580610
TI  - Genetic factors in common complex renal and cardiovascular diseases.
AB  - A minority of subjects exposed to prolonged elevations in systemic blood pressure
      or serum glucose concentrations will develop progressive albuminuria or reduced
      glomerular filtration rates. Individuals from families that have multiple members
      with chronic kidney disease and individuals of color are more likely to develop
      renal microvascular involvement from these systemic diseases. In contrast,
      individuals of color are significantly less likely to develop macrovascular
      coronary and carotid artery disease, compared with European Americans. Coronary
      artery disease and atherosclerosis also aggregate in families. Familial
      aggregation and ethnic-specific risk strongly implicates genetic susceptibility
      in the common etiologies of kidney disease and atherosclerosis. While
      acknowledging the importance of environmental and sociocultural effects, this
      manuscript explores genomic regions and genes of interest involved in
      susceptibility to common, complex kidney diseases. In contrast to the genes that
      have been determined to cause monogenic kidney diseases, as are highlighted
      throughout this issue of Advances in Chronic Kidney Disease, the identification
      of genes that underlie complex diseases has proven to be more challenging,
      expensive, and time consuming. Nonetheless, developments have been made in this
      important area.

PMID- 16580611
TI  - Epithelial Ca2+ and Mg2+ channels in kidney disease.
AB  - Many physiological functions rely on the precise maintenance of body calcium
      (Ca2+) and magnesium (Mg2+) balance, which is tightly regulated by the concerted
      actions of intestinal absorption, renal reabsorption, and exchange with bone. The
      kidney plays an important role in the homeostasis of divalent ions. Most Ca2+ and
      Mg2+ reabsorption occurs in the proximal tubules and the thick ascending limb of
      Henle's loop via a passive paracellular pathway. At the level of the distal
      convoluted tubule (DCT) and the connecting tubule (CNT), Ca2+ and Mg2+ are
      reabsorbed via an active transcellular route. Reabsorption of divalents in these
      latter segments is regulated in a Ca2+ and Mg2+-specific manner and determines
      the final excretion in the urine. Importantly, genetic studies, as well as
      molecular cloning strategies, recently identified epithelial ion channels as the
      gatekeepers of active Ca2+ and Mg2+ reabsorption. These channels are members of
      the transient receptor potential (TRP) superfamily. TRP vanilloid 5 (TRPV5) is
      responsible for the rate-limiting Ca2+ entry, and TRP melastatin 6 (TRPM6)
      constitutes the apical entry step in Mg2+ reabsorption. Dysregulation or
      malfunction of these influx pathways has been associated with renal Ca2+ and Mg2+
      wasting. This review updates the current knowledge and the recent advances of
      Ca2+ and Mg2+ reabsorption and related disorders.

PMID- 16580612
TI  - Inherited sodium avid states.
AB  - Several familial forms of hypertension have been identified, in which the
      mendelian pattern of inheritance indicated that hypertension results from the
      alteration of a single gene. This short review focuses on those rare monogenic
      disorders characterized by a low-renin profile. This common feature reflects that
      the causative mutations responsible for these disorders all result in an
      excessive sodium reabsorption in the aldosterone-dependent nephron. Low-renin
      familial hypertensions with hypokalemia encompass familial hyperaldosteronisms,
      in which aldosterone levels are elevated, and familial pseudohyperaldosteronisms,
      mimicking aldosteronism despite appropriately suppressed aldosterone levels. In
      these disorders, the avidity of the kidney for sodium is because of dysregulated
      sodium reabsorption through the epithelial sodium channel ENaC and results in
      potassium wasting and metabolic alcalosis. Familial hypertension with
      hyperkalemia is a specific syndrome resulting from mutations in at least 3
      different genes, among which 2 have been recently identified. These genes encode
      members of a new family of kinase, the WNK kinases, involved in the regulation of
      sodium and potassium excretion by the kidney.

PMID- 16580613
TI  - Genetic factors associated with gout and hyperuricemia.
AB  - Hyperuricemia and gout are common conditions that have long been known to have a
      heritable component. Obesity, diabetes, and chronic kidney failure are conditions
      with multifactorial inheritance that are associated with gout. In addition,
      social factors such as protein and alcohol intake affect serum uric acid levels.
      The current review discusses basic uric acid metabolism and the multigenetic
      inheritance of hyperuricemia. Several monogenic disorders affecting uric acid
      metabolism are reviewed. The genetics, pathophysiology, diagnosis, and treatment
      of familial juvenile hyperuricemic nephropathy/medullary cystic kidney disease,
      autosomal dominant disorders associated with hyperuricemia and progressive kidney
      failure, are described.

PMID- 16580614
TI  - Renal cystic disease: the role of the primary cilium/centrosome complex in
      pathogenesis.
AB  - Cystic diseases of the kidney are among the most frequent inherited disorders and
      constitute a significant cause of end-stage renal disease. Identification of the
      genes involved in these disorders and their protein products has provided key
      insights into the cellular processes that underlie cyst development and mediate
      disease progression. Of particular note, the proteins implicated in these
      disorders localize to the cilia/centrosome complex and have focused recent
      research on the role of this complex in the pathogenesis of renal cystic disease.
      Unraveling the spatial and functional relationship between these cystoproteins
      and the cilia/centrosome complex will undoubtedly provide a better understanding
      of the pathogenesis of cystic diseases and potentially offer windows for
      therapeutic intervention.

PMID- 16580615
TI  - Diagnosis and management of kidney involvement in Fabry disease.
AB  - Interest in the diagnosis and treatment of Fabry disease has been greatly
      stimulated by the availability of Food and Drug Administration-approved,
      effective enzyme replacement therapy. This review will update the progress in
      this area since enzyme replacement therapy has become available. Fabry disease is
      often associated with proteinuric chronic kidney disease (CKD), and it appears
      that the treatment paradigms that have proven to be so effective in diabetes
      mellitus and other forms of proteinuric kidney disease are also effective in
      conjunction with enzyme replacement therapy for treating the kidney
      manifestations of Fabry disease. As such, Fabry disease represents an interesting
      example of progressive proteinuric kidney disease in which the usual blood
      pressure is lower than in other forms of CKD. This makes the use of effective
      antiproteinuric therapy challenging, especially considering the autonomic
      dysfunction that appears to be part of the disease. Comprehensive therapy for
      Fabry disease includes enzyme replacement therapy and all of the adjunctive
      therapies that are currently used to treat all forms of proteinuric CKD. It is
      anticipated that this approach will preserve kidney function and also benefit the
      cardiac and cerebrovascular systems in patients with Fabry disease.

PMID- 16580616
TI  - Gitelman syndrome.
AB  - In the past decade our understanding of the etiology and pathophysiology of
      Gitelman syndrome, an autosomal recessive salt-losing tubular disorder with
      secondary hypokalemia, has increased considerably through the achievements of
      molecular genetics and cell physiology. In this short review, I will summarize
      the most recent data on the clinical and biochemical phenotype, the molecular
      causes, and the pathogenesis of Gitelman syndrome. I will especially focus on the
      recent elucidation of the mechanisms involved in the pathogenesis of the
      hypomagnesemia and hypocalciuria that accompanies Gitelman syndrome.

PMID- 16580618
TI  - The genetic basis of human glomerular disease.
AB  - Clinical and molecular research aimed to understand glomerular disease has
      emerged to one of the most active areas in renal research at large. The
      unraveling of genetic causes resulting in proteinuria has helped to define roles
      for each component of the glomerular filtration barrier in the development of
      urinary protein loss. Although most of the inherited glomerular diseases have in
      common defects in the podocyte, the glomerular basement membrane is also of
      critical importance for normal kidney permselectivity. This review summarizes
      recent progress in the eludication of genetic causes of glomerular disease and
      discusses their implications for the understanding of the pathogenic mechanisms,
      which can lead to disruption of the glomerular filtration barrier.

PMID- 16580617
TI  - Renal phosphate-wasting disorders.
AB  - The renal regulation of phosphate is a complex process. Clinical disorders of
      phosphate handling have led to the identification of several genes and proteins
      involved in the maintenance of phosphate homeostasis. Further work is required to
      elucidate the precise pathways that regulate renal phosphate transport.

PMID- 16580619
TI  - On the origin of genetics and beginnings of medical genetics of diseases of the
      kidney.
AB  - The twentieth century has been termed the century of the gene. Although the term
      "gene" was introduced in 1909, interest in reproduction and heredity has occupied
      humankind since its transition from hunter-gatherers to farmers and herders.
      Heredity, as it applies to diseases, began with Greek medicine. The humoral
      theory of the Hippocratic Corpus provided an etiological explanation for
      susceptibility of individuals to certain diseases well into the nineteenth
      century and was variously termed diathesis, temperament, and constitution. The
      application of the new probability math to quantify the hybridization of sweet
      peas by Gregor Mendel (1822-1884) in 1866 provided a scientific basis to
      inheritance, which had theretofore been an amalgam of scattered empirical
      observations. The near simultaneous publication of Origin of Species by Charles
      Darwin (1809-1882) in 1859 was a key catalyst in the transfer of what had been
      studies in plant biology into studies of populations and humans. The subsequent
      growth of genetics has been the outcome of interplay of technological
      breakthroughs in statistical analysis, cytology, biochemistry, physics, and
      computer science, coupled with the insightful analysis of workers in the field,
      several of whom have been the recipients of the Nobel Prize in medicine or
      chemistry since 1933. Application of these techniques to molecular biology and
      medical genetics is just beginning to yield insight into diseases of the kidney
      and provide visions of their likely therapies in the future.

PMID- 16580620
TI  - Policy implications of genetic testing: not just for geneticists anymore.
AB  - Genetic testing is expanding rapidly to become part of mainstream medicine. While
      genetic tests bring with them the promise of improved diagnosis and treatment for
      patients, they also raise several policy challenges. These challenges include the
      lack of a coherent oversight system to ensure the quality of tests and testing
      laboratories, the rise of direct-to-consumer genetic testing, the dearth of
      professional guidelines to assist the transition of genetic tests from research
      to medical practice, and the absence of federal legislation to protect the
      privacy of genetic information and prevent genetic discrimination.

PMID- 16580621
TI  - Association of kidney function with mortality in patients with chronic kidney
      disease not yet on dialysis: a historical prospective cohort study.
AB  - Significant mortality occurs in populations with chronic kidney disease (CKD),
      but the relative contributions of lower glomerular filtration rate (GFR) itself,
      accompanying comorbidities, and the numerous abnormalities that develop with
      advancing CKD are poorly studied. We examined all-cause predialysis mortality in
      861 United States veterans with CKD stage 3 to 5 not yet on dialysis. The
      association of GFR with mortality was analyzed by the Kaplan-Meier method, and
      the effects of several confounding variables on mortality were assessed in a Cox
      proportional-hazards model. Overall death rate was 102.1/1,000 person-years (95%
      CI: 90.2 to 115.6). Lower kidney function was associated with higher mortality
      (relative risk [95%CI] for GFR less than 20 v 41 to 60 mL/min/1.73 m2: 2.56 [1.61
      to 4.07], P<0.001) after adjustment for age, race, diabetes mellitus,
      cardiovascular disease, smoking status, body mass index, mean arterial pressure,
      serum albumin, blood cholesterol, haemoglobin, and 24-hour urine protein. For
      every 10 mL/min/1.73 m2 lower estimated GFR, the adjusted relative risk of
      mortality (95% CI) was 1.28 (1.12 to 1.45), P<0.001. Lower kidney function is
      associated with increased mortality in patients with moderate and advanced CKD.
      This association is present even after adjustment for several confounders.

PMID- 16580622
TI  - TheUniform Anatomical Gift Act and organ donation in the United States.
AB  - The Uniform Anatomical Gift Act (UAGA) and its periodic revisions provide a
      template for the creation and amendment of legislation to adjust public policy
      and align it with developments in medical practice. It is also a model for
      statutory response to societal change as well as changes in regulatory and
      judicial precedents. Conversely, the history of the UAGA shows the limits of
      legislation to achieve certain social goals.

PMID- 16580623
TI  - [Laparocopic repair of incisional hernias: a gold standard?].

PMID- 16580624
TI  - Rapid phase change of lipid microdomains in giant vesicles induced by conversion
      of sphingomyelin to ceramide.
AB  - To understand the role of sphingomyelinase (SMase) in the function of biological
      membranes, we have investigated the effect of conversion of sphingomyelin (SM) to
      ceramide (Cer) on the assembly of domains in giant unilamellar vesicles (GUVs).
      The GUVs were prepared from mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine
      (DOPC), N-palmitoly-D-erythro-sphingosine (C16Cer), N-palmitoyl-D-erythro
      sphingosylphosphorylcholine (C16SM) and cholesterol. The amounts of DOPC, sum of
      C16Cer and C16SM, and cholesterol were kept constant (the ratio of these four
      lipids is shown as 1:X:1-X:1 (molar ratio), i.e., X is C16Cer/(C16Cer+C16SM)).
      Shape and distribution of domains formed in the GUVs were monitored by a
      fluorescent lipid, Texas Red 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine
      (0.1 mol%). In GUVs containing low C16Cer (X=0 and 0.25), round-shaped domains
      labeled by the fluorescent lipid were present, suggesting coexistence of liquid
      ordered and disordered domains. In GUVs containing intermediate Cer concentration
      (X=0.5), the fluorescent domain covered most of GUV surface, which was surrounded
      by gel-like domains. Differential scanning calorimetry of multilamellar vesicles
      prepared in the presence of higher Cer concentration (X>or=0.5) suggested
      existence of a Cer-enriched gel phase. Video microscopy showed that the enzymatic
      conversion of SM to Cer caused rapid change in the domain structure: several
      minutes after the SMase addition, the fluorescent region spread over the GUV
      surface, within which regions with darker contrast existed. Image-based
      measurement of generalized polarization (GP) of 6-dodecanoyl-2
      dimethylaminonaphthalene (Laurdan), which is related to the acyl chain ordering
      of the lipids, was performed. Before the SMase treatment domains with high (0.65)
      and low (below 0.4) GP values coexisted, presumably reflecting the liquid-ordered
      and disordered domains; after the SMase treatment regions with intermediate GP
      values (0.5) and smaller regions with higher GP values (0.65) were present.
      Generation of Cer thus caused a phase transition from liquid-ordered and
      disordered phases to a gel and liquid phase.

PMID- 16580625
TI  - Membrane interactions of antimicrobial peptides from Australian tree frogs.
AB  - The skin secretions of amphibians are rich in host defence peptides. The membrane
      interactions of the antimicrobial peptides, aurein 1.2, citropin 1.1 and
      maculatin 1.1, isolated from Australian tree frogs, are reviewed. Although all
      three peptides are amphipathic alpha-helices, the mode of action of these
      membrane-active peptides is not defined. The peptides have a net positive charge
      and range in length from 13 to 21 residues, with the longest, maculatin 1.1,
      having a proline at position 15. Interestingly, alanine substitution at Pro-15
      leads to loss of activity. The effects of these peptides on phospholipid bilayers
      indicate different mechanisms for pore formation and lysis of model membranes,
      with the shorter peptides exhibiting a carpet-like mechanism and the longest
      peptide forming pores in phospholipid bilayer membranes.

PMID- 16580626
TI  - Modulating the expression of aquaporin genes in planta: A key to understand their
      physiological functions?
AB  - Aquaporins (AQPs) are believed to act as "cellular plumbers", allowing plants to
      rapidly alter their membrane water permeability in response to environmental
      cues. This study of AQP regulation at both the RNA and protein levels has
      revealed a large number of possible mechanisms. Currently, modulation of AQP
      expression in planta is considered the strategy of choice for elucidating the
      role of AQPs in plant physiology. This review highlights the fact that this
      strategy is complicated by many factors, such as the incomplete characterization
      of transport selectivity of the targeted AQP, the fact that AQPs might act as
      multifunctional channels with multiple physiological roles, and the number of
      post-translational regulation mechanisms. The classification of AQPs as
      constitutive or stress-responsive isoforms is also proposed.

PMID- 16580627
TI  - The effects of sexual assault-related intrusion suppression in the laboratory and
      natural environment.
AB  - Individuals with a history of sexual victimization often experience enduring
      intrusive thoughts associated with their assault history. Research suggests that
      the characteristic ways in which sexually assaulted individuals respond to
      aversive internal experiences (i.e., thoughts, emotions, etc.) can influence the
      psychological distress associated with these intrusions. This study investigated
      the effects of suppressing sexual assault-related intrusions in a sample of 61
      female college students with a history of adolescent or adult sexual assault and
      recent assault-related intrusions. Participants were randomly assigned to
      suppress or monitor intrusions during a laboratory task and for 48 h outside the
      laboratory. In contrast to study hypotheses, findings indicated that intrusion
      monitoring was associated with higher subjective distress than suppression both
      in the laboratory and in the natural environment. No differences were found for
      the frequency of intrusions between groups in the laboratory. However, modest
      evidence for a rebound effect in intrusion frequency was found outside the
      laboratory.

PMID- 16580628
TI  - The 5-HT2A serotoninergic receptor is expressed in the MCF-7 human breast cancer
      cell line and reveals a mitogenic effect of serotonin.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) has been described as a mitogen in a
      variety of cell types and carcinomas. It exerts its mitogenic effect by
      interacting with a wide range of 5-HT receptor types. Certain studies suggest
      that some selective serotonin re-uptake inhibitors promote breast cancer in
      animals and humans. This study attempts to clarify the role of serotonin in
      promoting the growth of neoplastic mammary cells. Expression of the 5-HT(2A)
      serotoninergic receptor subtype in MCF-7 cells was determined by RT-PCR, Western
      blotting, and immunofluorescence analysis. The mitogenic effect of 5-HT on MCF-7
      cells was determined by means of the MTT proliferation assay. We have
      demonstrated that the 5-HT(2A) receptor subtype is fully expressed in the MCF-7
      human breast cancer cell line, in terms of encoding mRNA and receptor protein.
      Automated sequencing has confirmed that the 5-HT(2A) receptor present in this
      cell line is identical to the 5-HT(2A) receptor found in human platelets and in
      human cerebral cortex. Furthermore, this receptor was found by immunofluorescence
      to be on the plasma membrane. MTT proliferation assays revealed that 5-HT and
      DOI, a selective 5-HT(2A) receptor subtype agonist, stimulated MCF-7 cell. These
      results indicate that 5-HT plays a mitogenic role in neoplastic mammary cells.
      Our data also indicate that 5-HT exerts this positive growth effect on MCF-7
      cells through, in part, the 5-HT(2A) receptor subtype, which is fully expressed
      in this cell line.

PMID- 16580629
TI  - SGT, a Hsp90beta binding partner, is accumulated in the nucleus during cell
      apoptosis.
AB  - In this study, we reported that small glutamine-rich TPR-containing protein (SGT)
      interacted with not only Hsp90alpha but also Hsp90beta. Confocal analysis showed
      that treatment of cells with Hsp90-specific inhibitor geldanamycin (GA) disrupted
      the interaction of SGT with Hsp90beta and this contributed to the increase of
      nuclear localization of SGT in HeLa cells. The increased nuclear localization of
      SGT was further confirmed by the Western blotting in GA-treated HeLa cells and
      H1299 cells. In our previous study, SGT was found to be a new pro-apoptotic
      factor, so we wondered whether the sub-cellular localization of SGT was related
      with cell apoptosis. By confocal analysis we found that the nuclear import of SGT
      was significantly increased in STS-induced apoptotic HeLa cells, which implied
      that the sub-cellular localization of SGT was closely associated with Hsp90beta
      and apoptosis.

PMID- 16580630
TI  - Establishment of a novel method for enriching osteoblast progenitors from adipose
      tissues using a difference in cell adhesive properties.
AB  - In the clinical field, cell-based therapies are used to treat bone defects.
      Adipose tissues contain many osteoblast progenitors, among other cell types. We
      separated mouse adipose tissue-derived stromal cells (ATSCs) according to their
      cell adhesive properties. Cells in a fraction adherent to the culture dishes 0.5h
      after inoculation (AF-0.5) had a potent ability to differentiate into both
      osteoblasts and adipocytes in vitro. Their differentiation pathways depended on
      the culture conditions. In these cells, the expression of marker genes for
      osteoblast differentiation was induced in osteogenic medium. Moreover, the AF-0.5
      cells, which were induced to differentiate into osteoblasts in vitro, formed
      abundant bone tissues in vivo. These results suggest that the AF-0.5 cells have
      been enriched with bi-potential progenitor cells destined for either osteoblasts
      or adipocytes. This simple and efficient method for preparing osteoblast
      progenitor cells from ATSCs may be utilized for bone defect treatment clinically.

PMID- 16580631
TI  - Protection against avian influenza H9N2 virus challenge by immunization with
      hemagglutinin- or neuraminidase-expressing DNA in BALB/c mice.
AB  - Avian influenza viruses of H9N2 subtype are widely spread in avian species. The
      viruses have recently been transmitted to mammalian species, including humans,
      accelerating the efforts to devise protective strategies against them. In this
      study, an avian influenza H9N2 virus strain (A/Chicken/Jiangsu/7/2002), isolated
      in Jiangsu Province, China, was used to infect BALB/c mice for adaptation. After
      five lung-to-lung passages, the virus was stably proliferated in a large quantity
      in the murine lung and caused the deaths of mice. In addition, we explored the
      protection induced by H9N2 virus hemagglutinin (HA)- and neuraminidase (NA)
      expressing DNAs in BALB/c mice. Female BALB/c mice aged 6-8 weeks were immunized
      once or twice at a 3-week interval with HA-DNA and NA-DNA by electroporation,
      respectively, each at a dose of 3, 10 or 30microg. The mice were challenged with
      a lethal dose (40x LD(50)) of influenza H9N2 virus four weeks after immunization
      once or one week after immunization twice. The protections of DNA vaccines were
      evaluated by the serum antibody titers, residual lung virus titers, and survival
      rates of the mice. The result showed that immunization once with not less than
      10microg or twice with 3microg HA-DNA or NA-DNA provided effective protection
      against homologous avian influenza H9N2 virus.

PMID- 16580632
TI  - Severe acute respiratory syndrome coronavirus protein 7a interacts with hSGT.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) 7a is an accessory
      protein with no known homologues. In this study, we report the interaction of a
      SARS-CoV 7a and small glutamine-rich tetratricopeptide repeat-containing protein
      (SGT). SARS-CoV 7a and human SGT interaction was identified using a two-hybrid
      system screen and confirmed with interaction screens in cell culture and cellular
      co-localization studies. The SGT domain of interaction was mapped by deletion
      mutant analysis and results indicated that tetratricopeptide repeat 2 (aa 125
      158) was essential for interaction. We also showed that 7a interacted with SARS
      CoV structural proteins M (membrane) and E (envelope), which have been shown to
      be essential for virus-like particle formation. Taken together, our results
      coupled with data from studies of the interaction between SGT and HIV-1 vpu
      indicated that SGT could be involved in the life-cycle, possibly assembly of SARS
      CoV.

PMID- 16580634
TI  - The tumor suppressor LKB1 induces p21 expression in collaboration with LMO4, GATA
      6, and Ldb1.
AB  - The LKB1/STK11 serine/threonine kinase is mutated in Peutz-Jeghers syndrome and
      various sporadic cancers such as lung adenocarcinoma. We show here that LKB1
      forms a complex with LMO4, GATA-6, and Ldb1, and enhances GATA-mediated
      transactivation in a kinase-dependent manner. We further demonstrate that LKB1
      has the potential to induce p21 expression in collaboration with LMO4, GATA-6,
      and Ldb1 through the p53-independent mechanism. Our findings suggest that LKB1
      regulates GATA-mediated gene expression and that this activity of LKB1 may be
      important for its tumor suppressor function.

PMID- 16580633
TI  - FRET-based monitoring of conformational change of the beta2 adrenergic receptor
      in living cells.
AB  - The beta(2) adrenergic receptor (beta(2)AR) is a G protein-coupled receptor that
      is selective to epinephrine. We demonstrate herein monitoring of an agonist
      induced conformational change of beta(2)AR in living cells. The monitoring method
      is based on fluorescence resonance energy transfer from a cyan fluorescent
      protein (CFP) to a biarsenical fluorophore, FlAsH, attached to the C-terminus,
      and the third intracellular loop (ICL3), respectively. Recombinant beta(2)ARs
      exhibited agonist-induced increases in the FlAsH/CFP emission ratio, indicating
      that the ICL3 approached the C-terminus upon activation. Since the emission ratio
      changes were on a time scale of seconds, the conformational change of beta(2)AR
      in living cells was more rapid than that of purified beta(2)AR measured in vitro.
      Interestingly, the direction of the emission ratio change of beta(2)AR was
      opposite to that of the norepinephrine-responsive alpha(2A) adrenergic receptor
      reported recently. It was suggested that this discrepancy corresponds directly to
      the diametric biological functions, i.e., the activation or inactivation of
      adenylyl cyclase.

PMID- 16580635
TI  - Enhanced phagocytosis of CD47-deficient red blood cells by splenic macrophages
      requires SHPS-1.
AB  - The interaction of CD47 on red blood cells (RBCs) with SHPS-1 on macrophages is
      implicated to prevent the phagocytosis of the former cells by the latter cells.
      Indeed, the rate of clearance of transfused CD47-deficient (CD47(-/-)) RBCs from
      the bloodstream of wild-type mice was markedly increased compared with wild-type
      RBCs. Conversely, the rate of clearance of transfused wild-type RBCs was markedly
      increased in mice that expressed a mutant form of SHPS-1 lacking most of the
      cytoplasmic region of the protein. However, we here found that the clearance of
      CD47(-/-) RBCs in SHPS-1 mutant mice was minimal. In addition, the phagocytosis
      of CD47(-/-) RBCs by splenic macrophages from SHPS-1 mutant mice was markedly
      reduced compared with wild-type macrophages. These results thus suggest an
      additional role for CD47 on RBCs in the negative regulation of phagocytosis by
      macrophages and in determination of the life span of circulating RBCs.

PMID- 16580636
TI  - Conserved serine residues in serotonin transporter contribute to high-affinity
      cocaine binding.
AB  - Serotonin transporter (SERT) is one of the key protein targets of cocaine.
      Despite intensive studies, it is not clear where cocaine binds to its targets and
      what residues are involved in cocaine binding. We have cloned the serotonin
      transporter from silkworm (Bombyx mori, bmSERT). When expressed in cultured
      cells, bmSERT is over 20-fold less sensitive to cocaine than Drosophila
      melanogaster SERT (dmSERT). We performed species-scanning mutagenesis using
      bmSERT and dmSERT. There are two adjacent threonine residues in transmembrane
      domain 12 of bmSERT where the corresponding residues are two serines in dmSERT
      and in all known mammalian monoamine transporters. Replacing the serine residues
      with threonines in dmSERT reduces cocaine sensitivity; while switching the two
      threonine residues in bmSERT to serines increased cocaine sensitivity. Mutations
      at the corresponding residues in dopamine transporter also changed cocaine
      affinity. Our results suggest that the conserved serine residues in SERT
      contribute to high-affinity cocaine binding.

PMID- 16580637
TI  - Oog1, an oocyte-specific protein, interacts with Ras and Ras-signaling proteins
      during early embryogenesis.
AB  - We previously identified an oocyte-specific gene, Oogenesin 1 (Oog1), that
      encodes 326 amino acids containing a leucine zipper structure and a leucine-rich
      repeat. In the present study, to identify the interacting proteins of Oog1, we
      performed a yeast two-hybrid screening using a GV-oocyte cDNA library and found
      that Ral guanine nucleotide dissociation stimulator (RalGDS) is the binding
      partner of Oog1. Coimmunoprecipitation assay confirmed the interaction between
      Oog1 and RalGDS proteins. Colocalization experiments provide the evidence that
      the nuclear localization of RalGDS depends on the expression of Oog1.
      Interestingly, RalGDS protein localized in the nucleus rather than the cytoplasm
      between late 1-cell and early 2-cell stages, the time when Oog1 localizes in the
      nucleus. We also examined the interaction between Oog1 and Ras by GST pull-down
      assay and revealed that Oog1 interacts with Ras in a GTP-dependent manner. These
      findings suggest a role of Oog1 as a Ras-binding protein.

PMID- 16580638
TI  - Altered phosphorylation of cytoskeletal proteins in mutant protein phosphatase 2A
      transgenic mice.
AB  - Protein phosphatase 2A (PP2A) is a family of heterotrimeric enzymes with diverse
      functions under physiologic and pathologic conditions such as Alzheimer's
      disease. All PP2A holoenzymes have in common a catalytic subunit C and a
      structural scaffolding subunit A. These core subunits assemble with various
      regulatory B subunits to form heterotrimers with distinct functions in the cell.
      Substrate specificity of PP2A in vitro is determined by regulatory subunits with
      leucine 309 of the catalytic subunit C playing a crucial role in the recruitment
      of regulatory subunits into the complex. Here we expressed a mutant form of
      Calpha, L309A, in brain and Harderian (lacrimal) gland of transgenic mice. We
      found an altered recruitment of regulatory subunits into the complex,
      demonstrating a role for the carboxyterminal leucine of Calpha in regulating
      holoenzyme assembly in vivo. This was associated with an increased
      phosphorylation of tau in brain and an impaired dephosphorylation of vimentin
      demonstrating that both cytoskeletal proteins are in vivo substrates of distinct
      PP2A holoenzyme complexes.

PMID- 16580640
TI  - Decreased polyphenol transport across cultured intestinal cells by a salivary
      proline-rich protein.
AB  - Tannins are polyphenols commonly found in plant-derived foods. When ingested they
      can have various harmful effects, but salivary proline-rich proteins (PRPs) may
      provide protection against dietary tannins. The aim of this study was to
      investigate whether basic PRPs, a major family of salivary proteins, can prevent
      intestinal absorption of tannin. To do so it was necessary first to characterize
      transport of pentagalloyl glucose (5GG), a hydrolysable tannin, across cultured
      epithelial cells. Using human intestinal epithelial cells (Caco-2 cells) it was
      found that a partial degradation of 5GG occurred during transepithelial transport
      resulting in the presence of 5GG as well as tetra- and trigalloyl glucose and
      glucose in the receiving compartment. The sodium-dependent glucose transporter
      SGLT1 played a role in apical (mucosal) to basolateral (serosal) transport and
      transport in the opposite direction was dependent on the multidrug resistance
      associated protein MRP2. An increased uptake from the apical compartment was seen
      when the basolateral receiving solution was human serum rather than a balanced
      salt solution. Transport both in apical-basolateral and basolateral-apical
      directions was reduced when 1B4, a human basic PRP, was added to the 5GG
      containing medium. This decrease closely paralleled the formation of insoluble
      5GG-1B4 complexes. It appears that the formation of insoluble tannin-protein
      complexes diminishes the uptake of 5GG and its metabolites. There is little
      evidence of other biological activities of basic PRPs so in contrast to other
      salivary proteins they may exert a biological function in the intestines.

PMID- 16580639
TI  - The opioid ligand binding of human mu-opioid receptor is modulated by novel
      splice variants of the receptor.
AB  - The pharmacological actions of morphine and morphine-like drugs, such as heroin,
      mediate primarily through the mu-opioid receptor (MOR). It has been proposed that
      the functional diversity of MOR may be related to alternative splicing of the MOR
      gene. Although a number of MOR mRNA splice variants have been reported, their
      biological function has been controversial. In this study, two novel splice
      variants of the human MOR gene were discovered. Splice variants 1 and 2 (here
      called the SV1 and SV2) retain different portions of intron I. In vitro
      translation of SV1 and SV2 produced proteins with the predicted molecular
      weights. The splice variant proteins were identical to the wild-type MOR-1 up to
      the first transmembrane domains, but were different after the first intracellular
      loop domains. SV1 and SV2 of hMOR were present in human neuroblastoma NMB cells
      and human whole brain confirmed by RT-PCR. In a receptor binding assay, cells
      expressing the SV1 and SV2 do not exhibit binding to [(3)H]diprenorphine. The
      formations of MOR.SV1 and MOR.SV2 heterodimers were demonstrated by co
      immunoprecipitation and bioluminescence resonance energy transfer between MOR and
      splice variants. Co-transfection of MOR-GFP and SV-DsRed gene showed that MOR and
      SV protein co-localized at the cytoplasmic membrane. In NMB cells expressing
      human MOR gene, transfection of SV1 or SV2 reduced binding activity of the
      endogenous MOR. These data support a potential role of SV1 and SV2 proteins as
      possible biological modulator of human mu-opioid receptor.

PMID- 16580641
TI  - Relative effects of phenolic constituents from Yucca schidigera Roezl. bark on
      Kaposi's sarcoma cell proliferation, migration, and PAF synthesis.
AB  - Yuccaols (A, B, C) are phenolic constituents isolated from Yucca schidigera bark
      characterized by unusual spirostructures made up of a C15 unit and a stilbenic
      portion closely related to resveratrol. These novel compounds are of particular
      interest for their antioxidant and anti-inflammatory properties. However, their
      effects on cell proliferation, migration, and platelet-activating factor (PAF)
      biosynthesis remain unknown. PAF, a potent mediator of inflammation, is known to
      promote angiogenesis and in vitro migration of endothelial cells and Kaposi's
      sarcoma (KS) cells. The objective of our study was to determine the effect of
      Yuccaols and resveratrol on the vascular endothelial growth factor (VEGF)-induced
      proliferation, migration, and PAF biosynthesis in KS cells. The results indicated
      that Yuccaols (25 microM) were more effective than resveratrol (25 microM) in
      inhibiting the VEGF-induced KS cell proliferation. Western blot analysis revealed
      that Yuccaols reduced the VEGF-induced phosphorylation of p38 and p42/44, thus
      indicating a possible interference with the mechanism underlying the VEGF
      stimulated cell proliferation. Furthermore, Yuccaols completely inhibited the
      VEGF-stimulated PAF biosynthesis catalyzed by the acetyl-CoA:lyso-PAF
      acetyltransferase and enhanced its degradation through the PAF-dependent CoA
      independent transacetylase (250% of control). In addition, Yuccaol C abrogated
      the PAF-induced cell motility whereas Yuccaol A and Yuccaol B reduced the cell
      migration from 7.6 microm/h to 6.1 microm/h and 5.6 microm/h, respectively. These
      results indicate that the anti-inflammatory properties attributed to Yucca
      schidigera can be ascribed to both resveratrol and Yuccaols and provide the first
      evidences of the anti-tumor and anti-invasive properties of these novel phenolic
      compounds.

PMID- 16580642
TI  - Frontal dopamine D(2/3) receptor binding in drug-naive first-episode
      schizophrenic patients correlates with positive psychotic symptoms and gender.
AB  - BACKGROUND: The aim of the study was to examine extrastriatal dopamine D(2/3)
      receptor binding and psychopathology in schizophrenic patients, and to relate
      binding potential (BP) values to psychopathology. METHODS: Twenty-five drug-naive
      schizophrenic patients and 20 healthy controls were examined with single-photon
      emission computerized tomography (SPECT) using the D(2/3)-receptor ligand
      [123I]epidepride. RESULTS: In the hitherto largest study on extrastriatal D(2/3)
      receptors we detected a significant correlation between frontal D(2/3) BP values
      and positive schizophrenic symptoms in the larger group of male schizophrenic
      patients, higher frontal BP values in male (n = 17) compared to female (n = 8)
      patients, and - in accordance with this - significantly fewer positive
      schizophrenic symptoms in the female patients. No significant differences in BP
      values were observed between patients and controls; the patients, however, had
      significantly higher BP in the right compared to the left thalamus, whereas no
      significant hemispheric imbalances were observed in the healthy subjects.
      CONCLUSIONS: The present data are the first to confirm a significant correlation
      between frontal D(2/3) receptor BP values and positive symptoms in male
      schizophrenic patients. They are in agreement with the hypothesis that frontal
      D(2/3) receptor activity is significant for positive psychotic symptoms.
      Additionally, the data support a thalamic hemispheric imbalance in schizophrenia.

PMID- 16580643
TI  - Histological and magnetic resonance imaging assessment of cortical layering and
      thickness in autism spectrum disorders.
AB  - BACKGROUND: Qualitative reports of the cerebral cortex in a small number of
      autism spectrum disorder (ASD) cases have suggested an increase in thickness and
      disruptions in migration and lamination patterns. METHODS: We examined postmortem
      ASD individuals and age-matched controls using magnetic resonance imaging (MRI)
      to evaluate total cortical thickness, and histological samples to evaluate the
      pattern of cortical layering. RESULTS: Overall, thickness measures from ASD
      subjects were equivalent to control cases. Individual regions showed marginal but
      nonsignificant thickness differences in the temporal lobes. Cortical thickness
      values in ASD subjects decreased significantly with age. Quantitative examination
      of proportional layer thickness in histological sections indicated that the
      pattern of cortical layering was largely undisturbed, while qualitative
      examination of these same samples revealed evidence of cell clustering and
      supernumerary cells in layer I and the subplate. These features were not severe
      and were never found in a majority of cases. CONCLUSIONS: These findings support
      limited disturbances in cortical cell patterning, but do not indicate a major
      deficit in the orderly migration of cortical neuroblasts during development, or
      their subsequent aggregation into the laminar pattern found in typically
      developing individuals.

PMID- 16580644
TI  - Tyrosine kinase phosphorylation of GABAA receptor subunits following chronic
      ethanol exposure of cultured cortical neurons of mice.
AB  - Previous studies from our laboratory revealed that acute ethanol exposure
      inhibits phosphorylation of mitogen-activated protein (MAP) kinase and
      extracellular signal-regulated kinases (ERK) in mice. In the present study, we
      have further investigated effect of chronic administration of ethanol on tyrosine
      kinase phosphorylation of GABA(A) receptor subunits in the mouse cultured
      cortical neurons. We observed that there was an up-regulation in tyrosine kinase
      phosphorylation of the GABA(A) receptor beta(2) and gamma(2) subunits following
      chronic ethanol exposure, whereas there was no effect on alpha(1) subunit of the
      GABA(A) receptor in the cultured cortical neurons of mice as determined by
      Western blotting. These results suggest a potential role for tyrosine kinase
      phosphorylation of some of the GABA(A) receptor subunits in chronic ethanol
      induced tolerance and dependence.

PMID- 16580645
TI  - Alzheimer's disease drugs promote neurogenesis.
AB  - Alzheimer's disease (AD) is associated with increased production of new neurons
      (neurogenesis), which may be directed at brain repair. However, the effect of
      drugs used to treat AD on neurogenesis is unknown. We administered tacrine,
      galantamine or memantine to mouse cerebral cortical cultures in vitro, and to
      mice in vivo, and measured neurogenesis by labeling newborn cells with
      bromodeoxyuridine (BrdU) and confirming their neuronal lineage by cell-type
      specific protein expression. All three drugs increased BrdU incorporation into
      cortical cultures in vitro by up to 40%, and increased BrdU labeling of cells in
      neuroproliferative regions of the adult mouse brain in vivo by 26-45%. BrdU
      labeling was associated with neuronal markers, such as Hu and betaIII tubulin.
      Thus, drugs used to treat AD increase cerebral neurogenesis both in vitro and in
      vivo, which may contribute to their therapeutic effects.

PMID- 16580646
TI  - Damage of the medial preoptic area impairs peripheral pilocarpine-induced
      salivary secretion.
AB  - The existence of neural connections between the medial preoptic area (MPOA) and
      the salivary glands and the increase in salivation by thermal or electrical
      stimulation of the MPOA have suggested an important role of MPOA in the control
      of salivary gland function. Although direct cholinergic activation of the
      salivary glands induces salivation, recent studies have suggested that salivation
      produced by i.p. pilocarpine may also depend on the activation of central
      mechanisms. Therefore, in the present study, we investigated the effects of
      bilateral electrolytic lesions of the MPOA on the salivation induced by i.p.
      pilocarpine. Adult male Holtzman rats (n = 11-12/group) with bilateral sham or
      electrolytic lesions of the MPOA were used. One, five, and fifteen days after the
      brain surgery, under ketamine anesthesia, the salivation was induced by i.p.
      pilocarpine (1 mg/kg of body weight), and saliva was collected using pre-weighed
      small cotton balls inserted into the animal's mouth. Pilocarpine-induced
      salivation was reduced 1 and 5 days after MPOA lesion (341 +/- 41 and 310 +/- 35
      mg/7 min, respectively, vs. sham lesions: 428 +/- 32 and 495 +/- 36 mg/7 min,
      respectively), but it was fully recovered at the 15th day post-lesion (561 +/- 49
      vs. sham lesion: 618 +/- 27 mg/7 min). Lesions of the MPOA did not affect
      baseline non-stimulated salivary secretion. The results confirm the importance of
      MPOA in the control of salivation and suggest that its integrity is necessary for
      the full sialogogue effect of pilocarpine. However, alternative mechanisms
      probably involving other central nuclei can replace MPOA function in chronically
      lesioned rats allowing the complete recovery of the effects of pilocarpine.

PMID- 16580647
TI  - Immunohistochemical study on the distribution of TRPC channels in the rat
      hippocampus.
AB  - In the present study, we performed immunohistochemistry using antibodies directed
      against TRPCs to study the localizations of these channels in rat hippocampus.
      The pyramidal cell bodies of CA1-3 areas and the granule cell bodies of the
      dentate gyrus were immunoreactive for TRPC1, TRPC3, TRPC4 and TRPC5. On the other
      hand, TRPC6 exhibited the cloud-like neuropil staining only in the molecular
      layer of the dentate gyrus. As a whole, the present study has clearly shown the
      localization of TRPCs in rat hippocampus and may provide useful data for the
      future investigations on the structural and functional properties of TRPCs.

PMID- 16580648
TI  - Function-specific blockage of M(1) and M(3) muscarinic acetylcholine receptors by
      VX and echothiophate.
AB  - Certain organophosphate (OP) cholinesterase inhibitors (ChEIs) are also known to
      bind to the muscarinic acetylcholine receptor (mAChR). The functional
      consequences of such binding were investigated here using the following OP
      compounds: VX, echothiophate, sarin, and soman. VX (charged at physiological pH)
      and echothiophate (formally charged) inhibited a specific signal transduction
      pathway in CHO cells expressing either the M(1) or M(3) mAChR. Hence, they
      blocked carbamylcholine (CCh)-induced cyclic adenosine monophosphate (cAMP)
      synthesis (muM) and had almost no effect on CCh-induced phosphoinositide (PI)
      hydrolysis. These substances were inactive on forskolin-induced cAMP inhibition
      signaling in CHO cells expressing M(2) mAChR. In binding studies, using [(3)H]-N
      methyl scopolamine ([(3)H]NMS) as the competitor ligand, the ChEIs, VX and
      echothiophate exhibited binding to rat cortical mAChR with K(i) values in the muM
      range. The non-charged compounds, sarin and soman, were inert in modulating both
      cAMP metabolism and PI hydrolysis in CHO cells expressing M(1), M(2), and M(3)
      mAChRs, and no binding was observed in presence of [(3)H]NMS. These data suggest
      that VX and echothiophate act as function-specific blockers via a non-classical
      path of antagonistic activity, implying the involvement of allosteric/ectopic
      binding site in M(1) and M(3) mAChRs. The functionally selective antagonistic
      behavior of echothiophate and VX makes them potential tools for dissecting the
      interactions of the mAChR with different G proteins.

PMID- 16580649
TI  - Extended therapeutic time window after focal cerebral ischemia by non-competitive
      inhibition of AMPA receptors.
AB  - In acute stroke, the therapeutic time window is a critical factor which may have
      contributed to the failure of several phase III clinical trials with so-called
      neuroprotective agents. Since cerebral glutamate levels are elevated for many
      hours in progressing stroke, we investigated the novel AMPA glutamate receptor
      antagonist ZK 187638 in rodent models of stroke using up to 12 h delays in the
      start of therapy after permanent occlusion of the middle cerebral artery (MCA).
      In rats, ZK 187638 reduced total infarct volume by 43% and 33% when therapy was
      started immediately or with a delay of 6 h, respectively, but no effect was
      observed after a 12 h delay. Dose-dependent decreases of total infarct volume (up
      to 42%) were measured in mice given the first injection of ZK 187638 6 h after
      permanent MCA occlusion. In conclusion, the AMPA receptor antagonist ZK 187638
      has a therapeutic time window of at least 6 h after permanent focal cerebral
      ischemia in rodents.

PMID- 16580650
TI  - Excitotoxic hippocampal neuron loss following sustained electrical stimulation of
      the perforant pathway in the mouse.
AB  - Prolonged electrical stimulation of the perforant pathway in the rat evokes
      epileptiform discharges in dentate granule cells and irreversibly damages hilar
      neurons. In this in vivo study, we demonstrate that similar perforant path
      stimulation in C57Bl/6 mice causes the same pattern of hippocampal neuron loss.
      Therefore, this mouse model of seizure-induced hippocampal injury can be used for
      a wide variety of studies in genetically altered conditions not available in
      rats.

PMID- 16580651
TI  - Addition of glycerol for improved methylation linkage analysis of
      polysaccharides.
AB  - A presolubilization procedure with the use of glycerol is shown to be applicable
      for the structural analysis of polysaccharides. Neutral, acidic, high-molecular
      weight and low-molecular-weight polysaccharides were solubilized in glycerol
      prior to methylation and subsequent linkage analysis by GC-MS. All four types of
      polysaccharides showed significant increases in derivatization following
      presolubilization as measured by recovery of partially methylated alditol
      acetates.

PMID- 16580652
TI  - Synthesis of 3-O-(beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl)-3'-O-(beta
      D-glucopyranosyl)tamarixetin, the putative structure of aescuflavoside A from the
      seeds of Aesculus chinensis.
AB  - 3-O-(beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl)-3'-O-(beta-D
      glucopyranosyl)tamarixetin, the putative flavonal glycoside named aescuflavoside
      A, isolated from the seeds of Aesculus chinensis, is synthesized via
      regioselective glycosylation of 7-O-benzyltamarixetin with glycosyl bromides
      under phase-transfer-catalyzed conditions.

PMID- 16580653
TI  - Endothelin is a dose-dependent trophic factor and a mitogen in small arteries in
      vivo.
AB  - OBJECTIVE: Endothelin (ET) modulates cellular processes relevant to vascular
      remodeling, but there is still some debate as to the potential of ET to be a
      trophic factor or a mitogen. Moreover, the signaling of ET in vivo to produce
      these effects is largely unknown. METHODS: 3H-leucine and 3H-thymidine
      incorporation in rat small mesenteric arteries was studied with several doses of
      ET-1 (0.1-10 pmol/kg/min) administered for 26 h in vivo. RESULTS: The EC50 for
      protein synthesis was four times lower than that of DNA synthesis, with maximal
      effects around 1 and 3 pmol/kg/min, respectively. At 5 pmol/kg/min, ET enhanced
      CDK2 activity by reducing the binding of its inhibitor p27(Kip1). In contrast,
      the binding was enhanced at 0.5 pmol/kg/min. The reduced binding observed at 5
      pmol/kg/min could not be explained by changes of p27(Kip1) or CDK2 content.
      Phosphorylation of p27(Kip1) on serine 10 was significantly reduced at 5
      pmol/kg/min ET. Although the phosphoinositide 3-kinase pathway was activated, it
      did not contribute to the protein or DNA synthesis responses. Administration of 1
      or 5 pmol/kg/min ET-1 for 28 days increased the thickness and cross-sectional
      area of the small mesenteric artery due to hypertrophy and hyperplasia,
      respectively, thus confirming the results obtained in acute conditions.
      CONCLUSION: ET modulates p27(Kip1) binding to CDK2, producing hypertrophy at low
      and hyperplasia at higher concentrations. Taken together, these results suggest
      that ET can act both as a trophic factor and as a mitogen in an in vivo
      environment, depending on its local concentration.

PMID- 16580654
TI  - DNA damage and repair in atherosclerosis.
AB  - There is increasing evidence that human atherosclerosis is associated with damage
      to the DNA of both circulating cells, and cells of the vessel wall. Reactive
      oxygen species are the most likely agents inducing DNA damage in atherosclerosis.
      DNA damage produces a variety of responses, including cell senescence, apoptosis
      and DNA repair. This review summarises the evidence for DNA damage in
      atherosclerosis, the cellular responses to damage and the mechanisms of
      signalling DNA damage.

PMID- 16580655
TI  - The role of oxidants and free radicals in reperfusion injury.
AB  - While timely reperfusion of acute ischemic myocardium is essential for myocardial
      salvage, reperfusion results in a unique form of myocardial damage. Functional
      alterations occur, including depressed contractile function and decreased
      coronary flow as well as altered vascular reactivity. Both myocardial stunning
      and infarction are seen. Over the last two decades, it has become increasingly
      clear that oxidant and oxygen radical formation is greatly increased in the post
      ischemic heart and serves as a critical central mechanism of post-ischemic
      injury. This oxidant formation is generated through a series of interacting
      pathways in cardiac myocytes and endothelial cells and triggers subsequent
      leukocyte chemotaxis and inflammation. Nitric oxide (NO) production and NO levels
      are also greatly increased in ischemic and post-ischemic myocardium, and this
      occurs through NO synthase (NOS)-dependent NO formation and NOS-independent
      nitrite reduction. Recently, it has been shown that the pathways of oxygen
      radical and NO generation interact and can modulate each other. Under conditions
      of oxidant stress, NOS can switch from NO to oxygen radical generation. Under
      ischemic conditions, xanthine oxidase can reduce nitrite to generate NO. NO and
      peroxynitrite can inhibit pathways of oxygen radical generation, and, in turn,
      oxidants can inhibit NO synthesis from NOS. Ischemic preconditioning markedly
      decreases NO and oxidant generation, and this appears to be an important
      mechanism contributing to preconditioning-induced myocardial protection.

PMID- 16580656
TI  - Protective effects of honokiol against oxidized LDL-induced cytotoxicity and
      adhesion molecule expression in endothelial cells.
AB  - Honokiol, a compound extracted from Chinese medicinal herb Magnolia officinalis,
      has several biological effects. However, its protective effects against
      endothelial injury remain unclarified. In this study, we examined whether
      honokiol prevented oxidized low-density lipoprotein (oxLDL)-induced vascular
      endothelial dysfunction. Incubation of oxLDL with honokiol (2.5-20 microM)
      inhibited copper-induced oxidative modification as demonstrated by diene
      formation, thiobarbituric acid reactive substances (TBARS) assay and
      electrophoretic mobility assay. Expression of adhesion molecules (ICAM, VCAM and
      E-selectin) and endothelial NO synthase (eNOS) affected by oxLDL was investigated
      by flow cytometry and Western blot. We also measured the production of reactive
      oxygen species (ROS) using the fluorescent probe 2',7'-dichlorofluorescein
      acetoxymethyl ester (DCF-AM). Furthermore, several apoptotic phenomena including
      increased cytosolic calcium, alteration of mitochondrial membrane potential,
      cytochrome c release and activation of caspase-3 were also investigated.
      Apoptotic cell death was characterized by terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling (TUNEL) stain. The results showed that honokiol
      prevented the copper-induced oxidative modification of LDL. Honokiol also
      ameliorated the oxLDL-diminished eNOS protein expression and reduced the oxLDL
      induced adhesion molecules and the adherence of THP-1 cells to HUVECs.
      Furthermore, honokiol attenuated the oxLDL-induced cytotoxicity, apoptotic
      features, ROS generation, intracellular calcium accumulation and the subsequent
      mitochondrial membrane potential collapse, cytochrome c release and activation of
      caspase-3. Our results suggest that honokiol may have clinical implications in
      the prevention of atherosclerotic vascular disease.

PMID- 16580657
TI  - Lipid lateral diffusion in bilayers with phosphatidylcholine, sphingomyelin and
      cholesterol. An NMR study of dynamics and lateral phase separation.
AB  - Pulsed field gradient (pfg)-NMR measurements of the lipid lateral diffusion
      coefficients in several macroscopically aligned bilayer systems were summarized
      from previous and new studies. The aim was to carry out a comparison of the
      translational dynamics for bilayers with various mixtures of l,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC), l,2-dipalmitoyl-sn-glycero-3-phosphocholine
      (DPPC) and chicken egg yolk sphingomyelin (eSM), with or without cholesterol. New
      useful information was obtained on the dynamics in these lipid bilayers that has
      not been previously appreciated. Thus, we were able to propose that the driving
      force behind the phase separation into l(d)and l(o)phases evolves from the
      increasing difficulty to incorpotate DOPC into a highly ordered phase. Our
      results suggest that DOPC has a preference to be located in a disordered phase,
      while DPPC and eSM prefer the ordered phase. Quite unexpectedly, CHOL seems to
      partition into both phases to roughly the same extent, indicating that CHOL has
      no particular preference for any of the l(d)or l(o) phases, and there are no
      specific interactions between CHOL and saturated lipids.

PMID- 16580658
TI  - Lipid-protein interactions with the Na,K-ATPase.
AB  - Studies of lipid interactions with membranous Na,K-ATPase by using electron spin
      resonance spectroscopy in conjunction with spin-labelled lipids are reviewed. The
      lipid stoichiometry, selectivity and exchange dynamics at the lipid-protein
      interface can be determined, in addition to information on the configuration and
      rotational dynamics of the protein-associated lipid chains. These parameters,
      particularly the stoichiometry and selectivity, are related directly to the
      intramembranous structure of the Na,K-ATPase, and can be used to check the
      integrity of extensively trypsinised preparations.

PMID- 16580659
TI  - Diagnostic and prognostic role of cardiac troponin I (cTnI) measured on the DPC
      Immulite.
AB  - OBJECTIVE: To evaluate the diagnostic and prognostic role of the Immulite cTnI
      assay for the detection of acute coronary syndromes (ACS). POPULATION: 150 males
      and 63 females with a median age of 63 years, range 28 to 88, and an
      interquartile range of 18 years were admitted within 24 h of chest pain and non
      ST segment elevation ACS were studied. The median onset of symptoms was 3 h
      (range 0-23). METHODS: Venous samples were taken on admission (t = 0) and at 24 h
      (t = 24). The serum samples were assayed for CK, CK-MB and cTnT on an Elecsys
      1010 (Roche Diagnostics, Lewes, UK). The cTnT assay CV was 5.5% at 0.32 microg/l
      and 5.4% at 6.0 microg/l, and the detection limit was 0.01 microg/l with an upper
      limit of 25 microg/l. For cTnI using the Immulite (DPC, Gwynedd, Wales), the
      detection limit was 0.1 microg/l, and the upper limit was 180 microg/l. Final
      diagnostic categorization was performed by both WHO and European Society of
      Cardiology criteria using cTnT as the diagnostic cardiac biomarker. Patients were
      followed for the major adverse cardiac events (MACE), endpoints cardiac death,
      AMI or need for urgent revascularization. ROC curves were constructed using final
      diagnosis. Outcome prediction was assessed by ROC curves and Kaplan-Meier
      survival curves. RESULTS: Both methods had equivalent diagnostic efficiency using
      WHO criteria for AMI. When ESC criteria were used the AUC for admission and 24 h
      cTnT and cTnI values were 0.945 vs. 0.910, P = 0.20 and 0.998 vs. 0.937, P =
      0.005, respectively. Both methods predicted outcome as either death or MI or MACE
      and were not significantly different. CONCLUSION: The Immulite cTnI assay can be
      used for diagnosis and risk stratification in patients admitted with non-ST
      segment elevation acute coronary syndromes.

PMID- 16580660
TI  - A switch from MafB to MafA expression accompanies differentiation to pancreatic
      beta-cells.
AB  - Major insulin gene transcription factors, such as PDX-1 or NeuroD1, have equally
      important roles in pancreatic development and the differentiation of pancreatic
      endocrine cells. Previously, we identified and cloned another critical insulin
      gene transcription factor MafA (RIPE3b1) and reported that other Maf factors were
      expressed in pancreatic endocrine cells. Maf factors are important regulators of
      cellular differentiation; to understand their role in differentiation of
      pancreatic endocrine cells, we analyzed the expression pattern of large-Maf
      factors in the pancreas of embryonic and adult mice. Ectopically expressed large
      Maf factors, MafA, MafB, or cMaf, induced expression from insulin and glucagon
      reporter constructs, demonstrating a redundancy in their function. Yet in adult
      pancreas, cMaf was expressed in both alpha- and beta-cells, and MafA and MafB
      showed selective expression in the beta- and alpha-cells, respectively.
      Interestingly, during embryonic development, a significant proportion of MafB
      expressing cells also expressed insulin. In embryos, MafB is expressed before
      MafA, and our results suggest that the differentiation of beta-cells proceeds
      through a MafB+ MafA- Ins+ intermediate cell to MafB- MafA+ Ins+ cells.
      Furthermore, the MafB to MafA transition follows induction of PDX-1 expression
      (Pdx-1(high)) in MafB+ Ins+ cells. We suggest that MafB may have a dual role in
      regulating embryonic differentiation of both beta- and alpha-cells while MafA may
      regulate replication/survival and function of beta-cells after birth. Thus, this
      redundancy in the function and expression of the large-Maf factors may explain
      the normal islet morphology observed in the MafA knockout mice at birth.

PMID- 16580662
TI  - Cytokinesis in plant and animal cells: endosomes 'shut the door'.
AB  - For many years, cytokinesis in eukaryotic cells was considered to be a process
      that took a variety of forms. This is rather surprising in the face of an
      apparently conservative mitosis. Animal cytokinesis was described as a process
      based on an actomyosin-based contractile ring, assembling, and acting at the cell
      periphery. In contrast, cytokinesis of plant cells was viewed as the centrifugal
      generation of a new cell wall by fusion of Golgi apparatus-derived vesicles.
      However, recent advances in animal and plant cell biology have revealed that many
      features formerly considered as plant-specific are, in fact, valid also for
      cytokinetic animal cells. For example, vesicular trafficking has turned out to be
      important not only for plant but also for animal cytokinesis. Moreover, the
      terminal phase of animal cytokinesis based on midbody microtubule activity
      resembles plant cytokinesis in that interdigitating microtubules play a decisive
      role in the recruitment of cytokinetic vesicles and directing them towards the
      cytokinetic spaces which need to be plugged by fusing endosomes. Presently, we
      are approaching another turning point which brings cytokinesis in plant and
      animal cells even closer. As an unexpected twist, new studies reveal that both
      plant and animal cytokinesis is driven not so much by Golgi-derived vesicles but
      rather by homotypically and heterotypically fusing endosomes. These are generated
      from cytokinetic cortical sites defined by preprophase microtubules and
      contractile actomyosin ring, which induce local endocytosis of both the plasma
      membrane and cell wall material. Finally, plant and animal cytokinesis meet
      together at the physical separation of daughter cells despite obvious differences
      in their preparatory events.

PMID- 16580661
TI  - MAU-8 is a Phosducin-like Protein required for G protein signaling in C. elegans.
AB  - The mau-8(qm57) mutation inhibits the function of GPB-2, a heterotrimeric G
      protein beta subunit, and profoundly affects behavior through the Galphaq/Galphao
      signaling network in C. elegans. mau-8 encodes a nematode Phosducin-like Protein
      (PhLP), and the qm57 mutation leads to the loss of a predicted phosphorylation
      site in the C-terminal domain of PhLP that binds the Gbetagamma surface
      implicated in membrane interactions. In developing embryos, MAU-8/PhLP localizes
      to the cortical region, concentrates at the centrosomes of mitotic cells and
      remains associated with the germline blastomere. In adult animals, MAU-8/PhLP is
      ubiquitously expressed in somatic tissues and germline cells. MAU-8/PhLP
      interacts with the PAR-5/14.3.3 protein and with the Gbeta subunit GPB-1. In mau
      8 mutants, the disruption of MAU-8/PhLP stabilizes the association of GPB-1 with
      the microtubules of centrosomes. Our results indicate that MAU-8/PhLP modulates G
      protein signaling, stability and subcellular location to regulate various
      physiological functions, and they suggest that MAU-8 might not be limited to the
      Galphaq/Galphao network.

PMID- 16580663
TI  - A novel adamantane derivative attenuates retinal ischemia-reperfusion damage in
      the rat retina through sigma1 receptors.
AB  - The effects of a novel N-methyladamantan-1-amine derivative [(-)-MR22] with high
      sigma1 receptor affinity were investigated on retinal degeneration using a rat
      model of ischemia-reperfusion injury. The animals were anaesthetized and retinal
      ischemia was induced by elevating the intraocular pressure to 120 mm Hg for 45
      min. The drug was injected intraperitoneally before the ischemic damage. Retinal
      biochemical changes, i.e. increase of lactate content and decrease of glucose and
      ATP were significantly inhibited by the new and selective sigma1 receptor ligand
      compared to the ischemic control group. The effect of (-)-MR22 was antagonized by
      pre-treatment with the sigma1 site antagonist. The protective effect of (-)-MR22
      on ischemic retina was confirmed by the histological analysis. These findings
      suggest that (-)-MR22 serves as a retinal neuroprotective agent and acts as a
      sigma1 receptor agonist.

PMID- 16580664
TI  - Temporal transcriptome of mouse ATDC5 chondroprogenitors differentiating under
      hypoxic conditions.
AB  - The formation of cartilage takes place in vivo in an environment of reduced
      oxygen tension. To study the effect of hypoxia on the process of chondrogenesis,
      ATDC5 mouse chondroprogenitor cells were induced to differentiate by the addition
      of insulin and cultured under ambient and hypoxic conditions corresponding to 21%
      and 1% O2 in the gas phase, respectively. The production of extracellular
      proteoglycans as well as the transcriptional profile of 104 selected genes was
      determined by real-time RT-PCR. Hypoxia alone induced early chondrogenesis as
      evidenced by the synthesis of glycosaminoglycans and expression of aggrecan and
      collagen type II genes. Surprisingly, however, hypoxic incubation of insulin
      treated cells delayed and suppressed the insulin-mediated early chondrogenesis
      and almost completely blocked hypertrophic differentiation. Analysis of the gene
      expression yielded several clues as to the mechanisms involved. In addition, a
      group of genes was identified that have not previously been associated with
      hypoxia, including Ak4, Akt3, Col X, Fmod, Ier3, IGFbp4, MafF, Mxi1, Rcor2, Rras,
      Sox6, Tnni2, Wnt5a, and Zfp313.

PMID- 16580665
TI  - A cholesterol-enriched diet induces ultrastructural changes in retinal and
      macroglial rabbit cells.
AB  - The purpose of this study was to ascertain whether the excess of cholesterol in
      rabbits induces ultrastructural retinal changes similar to those observed in
      human age-related macular degeneration (AMD). New Zealand rabbits were divided
      into two groups: Control (GO; n=10), fed standard diet for 8 months;
      hypercholesterolemic (G1; n=10), fed with 0.5% cholesterol-enriched diet for 8
      months. Eyes were processed for transmission electron microscopy (TEM) and
      immunohistochemistry (anti-glial fibrillary acidic protein, GPAP). In comparison
      with GO, G1 exhibited alterations in all the retinal layers that were more
      intense in areas overlying altered retinal pigment epithelium (RPE). RPE changes
      showed no preferential location. In G1, Bruch's membrane was thicker as a result
      particle build-up in the collagen layers; the cytoplasm of RPE showed dense
      bodies, debris from cell membranes, vacuoles and numerous clumps of lipids;
      necrosis and apoptosis were detected in different retinal layers; Muller cells
      and astrocytes were reactive with instances of apoptosis and necrosis; some
      Muller cells filled up the empty spaces left by degenerated neurons in all
      retinal layers; some Muller cell nuclei were displaced to the nerve-fiber layer
      (NFL); epiretinal perivascular astrocytes contained drops of lipids; the NFL had
      very few astrocytes and the basal membranes of capillaries in the NFL was
      thicker. Excess cholesterol induces ultrastructural changes in the rabbit retina
      similar to those in human AMD. Given that lipid intake is most dependent on food
      composition, dietary regimen could help induce or prevent retinal disease.

PMID- 16580666
TI  - Corneal integrins and their functions.
AB  - Integrins were first described just over 20 years ago and have been studied in
      the cornea by many groups interested in how the cornea functions in health and
      disease. There are a minimum of 12 different integrin heterodimers reported to be
      expressed by the major resident cells of the cornea: the corneal and limbal
      epithelial cells, keratocytes/fibroblasts, and corneal endothelial cells. These
      different integrin heterodimers play important and varied roles in maintaining
      the cornea and organizing how its cells interact with their surrounding
      extracellular matrix to maintain corneal clarity. In this review, an overview of
      the discovery and functions of integrins is provided along with a description of
      the current state of our knowledge of this large family of important proteins.
      While we have learned a lot about corneal integrins over the past 20 years, there
      is still much to learn. Areas where gaps in our knowledge of integrin functions
      in the cornea are slowing our progress in understanding corneal diseases and
      dystrophies at a molecular level are highlighted.

PMID- 16580667
TI  - DU-145 and PC-3 human prostate cancer cell lines express androgen receptor:
      implications for the androgen receptor functions and regulation.
AB  - The majority of human prostate cancer cell lines, including the two "classical"
      cell lines DU-145 and PC-3, are reported to be androgen receptor (AR)-negative.
      However, other studies have provided evidence that the DU-145 and PC-3 cell lines
      express AR mRNA. These contradictory observations prompted us to investigate
      whether DU-145 and PC-3 cell lines express the androgen receptor. Using
      antipeptide antibodies directed against three distinct regions of the human AR
      protein and an improved method to detect AR protein in immunoblotting, we report
      that DU-145 and PC-3 cell lines express AR protein. We found that the relative
      levels of the AR mRNA and protein that were detected in DU-145 and PC-3 cell
      lines were lower than the LNCaP, an AR-positive cell line. Moreover, the antibody
      directed against the non-variant region (amino acids 299-315), but not the
      variant N- or C-terminal region (amino acids 1-20 and 900-919, respectively) of
      the human AR protein, detected the expression of AR in all prostate cancer cell
      lines. Notably, treatment of these cell lines with dihydrotestosterone (DHT)
      resulted in measurable increases in the AR protein levels and considerable
      nuclear accumulation. Although, treatment of DU-145 and PC-3 cells with DHT did
      not result in stimulation of the activity of an AR-responsive reporter, knockdown
      of AR expression in PC-3 cells resulted in decreases in p21(CIP1) protein levels,
      and a measurable decrease in the activity of the p21-luc-reporter. Our
      observations demonstrate the expression of AR protein in DU-145 and PC-3 prostate
      cancer cell lines.

PMID- 16580668
TI  - Unusual histone modifications in Trypanosoma brucei.
AB  - To start to understand the role of chromatin structure in regulating
      transcription in trypanosomes, we analyzed covalent modifications on the four
      core histones of Trypanosoma brucei. We found unusually few modifications in the
      N-terminal tails, which are abundantly modified in other organisms and whose
      sequences, but not composition, are highly divergent in trypanosomes. In
      contrast, the C-terminal region of H2A appears to be hyper-acetylated.
      Surprisingly, the N-terminal alanines of H2A, H2B, and H4, were mono-methylated,
      a modification that has not been described previously for histones. Possible
      functions and evolutionary explanations for these unusual histone modifications
      are discussed.

PMID- 16580669
TI  - Molecular nature of methicillin-resistant Staphylococcus aureus derived from
      explosive nosocomial outbreaks of the 1980s in Japan.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) with
      Panton-Valentine leukocidin (PVL) genes is increasing worldwide. Nosocomial
      outbreak-derived (hospital-acquired) MRSA (HA-MRSA) in Japan in the 1980s was
      also largely PVL(+). PVL(+) HA-MRSA and CA-MRSA shared the same multi-locus
      sequence type (ST30) and methicillin resistance cassette (SCCmecIV), but were
      divergent in oxacillin resistance, spa typing, PFGE analysis or clfA gene
      analysis. PVL(+) HA-MRSA, which probably originated in PVL(+)S. aureus ST30, was
      highly adhesive (carrying cna and bbp genes), highly-toxic (carrying luk(PV) and
      sea genes) and highly drug-resistant. PVL(+) HA-MRSA was once replaced by other
      PVL(-) HA-MRSA (e.g., ST5), and is re-emerging as CA-MRSA.

PMID- 16580671
TI  - Endoplasmic reticulum: a metabolic compartment.
AB  - Several biochemical reactions and processes of cell biology are compartmentalized
      in the endoplasmic reticulum (ER). The view that the ER membrane is basically a
      scaffold for ER proteins, which is permeable to small molecules, is inconsistent
      with recent findings. The luminal micro-environment is characteristically
      different from the cytosol; its protein and glutathione thiols are remarkably
      more oxidized, and it contains a separate pyridine nucleotide pool. The substrate
      specificity and activity of certain luminal enzymes are dependent on selective
      transport of possible substrates and co-factors from the cytosol. Abundant
      biochemical, pharmacological, clinical and genetic data indicate that the barrier
      function of the lipid bilayer and specific transport activities in the membrane
      make the ER a separate metabolic compartment.

PMID- 16580670
TI  - Fusogenic potential of sperm membrane lipids: nature's wisdom to accomplish
      targeted gene delivery.
AB  - The membrane-membrane fusion during fertilization of oocyte by spermatozoa is
      believed to be mainly mediated by so called "fusion proteins". In the present
      study we have tried to demonstrate that beside the proteins, lipid components of
      membrane may play an important role in fusion of oocyte with spermatozoa.
      Conventional membrane-membrane fusion assays were used as means to demonstrate
      fusogenic potential of human sperm membrane lipids. The liposomes (spermatosomes)
      made of the lipids isolated from sperm membrane were found to undergo strong
      membrane-membrane fusion as evident from fluorescence dequenching and resonance
      energy transfer assays. Furthermore, the fusion of these liposomes with living
      cells (J774 A.1 macrophage cell line) was demonstrated to result in an effective
      transfer of a water-soluble fluorescent probe (calcein) to cytosol of the target
      cell. Lastly, the liposomes were demonstrated to behave like efficient vehicles
      for the in vivo cytosolic delivery of the antigens to target cells resulting in
      elicitation of antigen specific CD8(+) T cell responses.

PMID- 16580672
TI  - Decreased neuroactive steroids induced by combined oral contraceptive pills are
      not associated with mood changes.
AB  - OBJECTIVE: To evaluate the effects of a low-dose combined oral contraceptive pill
      (OCP) on peripheral neuroactive steroid concentrations, precursors for
      neuroactive steroid synthesis, and mood in healthy women desiring contraception.
      These neuroactive steroids are gamma-aminobutyric acid receptor agonists and are
      important in the modulation of affect and adaptation to stress. DESIGN:
      Prospective observational study. SETTING: Human ambulatory patient study.
      PATIENT(S): Healthy OCP-naive women without current or history of affective
      disorder. INTERVENTION(S): A 0.020-mg ethinyl E2-0.1-mg levonorgestrel containing
      OCP for 3 months. MAIN OUTCOME MEASURE(S): Serum neuroactive steroids
      allopregnanolone, allotetrahydrodeoxycorticosterone, and DHEA; neuroactive
      steroid precursors P and pregnenolone; E2; and mood and anxiety as assessed by
      the Premenstrual Syndrome Daily Ratings Form, Beck Depression Inventory,
      Spielberger State-Trait Anxiety Inventory, and Profile of Mood States. RESULT(S):
      The combined OCP resulted in a decrease in neuroactive steroids and neuroactive
      steroid precursors as well as in E2. However, this decline was not associated
      with adverse mood changes on any of the well-validated assessment tools.
      CONCLUSION(S): Healthy women without underlying mood or anxiety disorder who were
      given a low-dose OCP did not experience adverse psychological symptoms despite a
      significant reduction in neuroactive steroids.

PMID- 16580673
TI  - Ovarian response to gonadotropins after laparoscopic salpingectomy or the
      division of fallopian tubes for hydrosalpinges.
AB  - OBJECTIVE: To compare the effect of prophylactic laparoscopic salpingectomy
      versus division of the fallopian tubes on ovarian response to gonadotropins in
      women undergoing IVF. DESIGN: Retrospective study. SETTING: National Health
      Service-based tertiary referral center for reproductive medicine. PATIENT(S): One
      hundred sixty-eight women with tubal factor infertility. Sixty-five women with
      hydrosalpinges had either salpingectomy (n = 40, group A) or proximal tubal
      division (n = 25, group B), while the remaining women with tubal disease but
      without hydrosalpinges acted as the control group (n = 103, group C).
      INTERVENTION(S): Prophylactic laparoscopic salpingectomy or proximal division of
      the fallopian tubes and ovarian stimulation with gonadotropins for IVF. MAIN
      OUTCOME MEASURE(S): Day 2 serum FSH levels before surgery and 3 months after
      surgery but before ovarian stimulation, ovarian response assessed as total dose
      of hMG administered, serum E2 concentrations on day 3 and day 8 of stimulation
      and on the day of hCG injection, number of follicles, and number of oocytes
      retrieved and fertilized. RESULT(S): In group A, baseline FSH levels were
      significantly raised after surgery compared with before surgery. Postsurgery FSH
      concentrations were significantly higher in group A compared with group B. The
      number of follicles (15-20 mm) was significantly lower in group A compared with
      group B and group C. The serum E2 levels on day 8 of stimulation were lower in
      group A compared with group B, and on the day of hCG injection it was
      significantly reduced in group A compared with groups B and C. The number of
      oocytes retrieved per cycle was significantly lower in group A compared with
      group B. There were no significant differences in pregnancy rates and miscarriage
      rates among the three groups. CONCLUSION(S): These findings suggest that
      prophylactic salpingectomy in women with hydrosalpinx may compromise ovarian
      response to stimulation without affecting pregnancy rates. A randomized control
      trial is recommended to determine the most appropriate laparoscopic procedure in
      the management of hydrosalpinx before IVF.

PMID- 16580674
TI  - Re: Should the tibia be reamed when nailing? [Injury 36 (2005) 439-444].

PMID- 16580676
TI  - Leptin and atherosclerosis.
AB  - Leptin, a 167-amino acid peptide hormone produced by white adipose tissue, is
      primarily involved in the regulation of food intake and energy expenditure.
      Leptin receptors are expressed in many tissues including the cardiovascular
      system. Plasma leptin concentration is proportional to body adiposity and is
      markedly increased in obese individuals. Recent studies suggest that
      hyperleptinemia may play an important role in obesity-associated cardiovascular
      diseases including atherosclerosis. Leptin exerts many potentially atherogenic
      effects such as induction of endothelial dysfunction, stimulation of inflammatory
      reaction, oxidative stress, decrease in paraoxonase activity, platelet
      aggregation, migration, hypertrophy and proliferation of vascular smooth muscle
      cells. Leptin-deficient and leptin receptor-deficient mice are protected from
      arterial thrombosis and neointimal hyperplasia in response to arterial wall
      injury. Several clinical studies have demonstrated that high leptin level
      predicts acute cardiovascular events, restenosis after coronary angioplasty, and
      cerebral stroke independently of traditional risk factors. In addition, plasma
      leptin correlates with markers of subclinical atherosclerosis such as carotid
      artery intima-media thickness and coronary artery calcifications. Inhibition of
      leptin signaling may be a promising strategy to slow the progression of
      atherosclerosis in hyperleptinemic obese subjects.

PMID- 16580675
TI  - Genetic variability at the leptin receptor (LEPR) locus is a determinant of
      plasma fibrinogen and C-reactive protein levels.
AB  - OBJECTIVE: Cellular and animal studies suggest that leptin has proinflammatory
      and prothrombotic effects that could link increased adipose mass directly to
      atherogenesis. To investigate this hypothesis, we examined the effect of genetic
      variability at the leptin receptor (LEPR) locus on the plasma levels of
      fibrinogen and CRP--two markers of inflammation and susceptibility to
      atherosclerosis. METHODS AND RESULTS: Linkage disequilibrium analysis of 71
      single-nucleotide polymorphisms (SNPs) spanning the LEPR locus revealed four
      haplotype blocks that could be tagged by 11 SNPs. In 630 healthy Caucasian
      individuals, variability in block #4 was significantly associated with plasma
      fibrinogen (p=0.005), accounting for 3% of its variance (r2=0.030). The same
      block was also associated with CRP levels (p=0.049, r2=0.022). The effect was
      strongest for two of the SNPs in this block. At rs3790432, fibrinogen was 10%
      higher in minor allele homozygotes than in major allele homozygotes and
      intermediate in heterozygotes (p=0.015). At rs1805096, it was 5% higher (p=0.007)
      and CRP 32% higher (p=0.011) in major allele homozygotes than in minor allele
      carriers. This pattern of association was also evident in the haplotype analysis.
      CONCLUSIONS: Association of leptin receptor variability with inflammatory traits
      supports the hypothesis that leptin may play a role in atherogenesis.

PMID- 16580677
TI  - Rapid determination of acrylamide contaminant in conventional fried foods by gas
      chromatography with electron capture detector.
AB  - Gas chromatography coupled with electron capture detector (GC-ECD) was
      successfully developed and applied for the rapid determination of acrylamide in
      conventional fried foods, such as potato crisps, potato chips, and fried chicken
      wings. The method included defatting with n-hexane, extraction with aqueous
      solution of sodium chloride (NaCl), derivatization with potassium bromate (KBrO3)
      and potassium bromide (KBr), and liquid-liquid extraction with ethyl acetate. The
      final acrylamide extract was analyzed by GC-ECD for quantification and by GC-MS
      for confirmation. The chromatographic analysis was performed on the HP-INNOWax
      capillary column, and good retention and peak response of acrylamide were
      achieved under the optimal conditions (numbers of theoretical plates N = 83,815).
      The limit of detection (LOD) was estimated to be 0.1 microg kg(-1) on the basis
      of ECD technique. Recoveries of acrylamide from conventional samples spiked at
      levels of 150, 500 and 1000 microg kg(-1) (n = 4 for each level) ranged between
      87 and 97% with relative standard deviations (RSD) of less than 4%. Furthermore,
      the GC-ECD method showed that no clean-up steps of acrylamide derivative would be
      performed prior to injection and was slightly more sensitive than the MS/MS-based
      methods. Validation and quantification results demonstrated that this method
      should be regarded as a new, low-cost, and robust alternative for conventional
      investigation of acrylamide.

PMID- 16580678
TI  - Adsorption mechanism in reversed-phase liquid chromatography. Effect of the
      surface coverage of a monomeric C18-silica stationary phase.
AB  - The effect of the bonding density of the octadecyl chains onto the same silica on
      the adsorption and retention properties of low molecular weight compounds
      (phenol, caffeine, and sodium 2-naphthalene sulfonate) was investigated. The same
      mobile phase (methanol:water, 20:80, v/v) and temperature (T = 298 K) were
      applied and two duplicate columns (A and B) from each batch of packing material
      (neat silica, simply endcapped or C1 phase, 0.42, 1.01, 2.03, and 3.15
      micromol/m2 of C18 alkyl chains) were tested. Adsorption data of the three
      compounds were acquired by frontal analysis (FA) and the adsorption energy
      distributions (AEDs) were calculated using the expectation-maximization method.
      Results confirmed earlier findings in linear chromatography of a retention
      maximum at an intermediate bonding density. From a general point of view, the
      saturation capacity of the adsorbent tends to decrease with increasing bonding
      density, due to the vanishing space intercalated between the C18 bonded chains
      and to the decrease of the specific surface area of the stationary phase. The
      equilibrium constants are maximum for an intermediary bonding density
      (approximately 2 micromol/m2). An enthalpy-entropy compensation was found for the
      thermodynamic parameters of the isotherm data. Weak equilibrium constants (small
      deltaH) and high saturation capacities (large deltaS) were observed at low
      bonding densities, higher equilibrium constants and lower saturation capacities
      at high bonding densities, the combinations leading to similar apparent retention
      in RPLC. The use of a low surface coverage column is recommended for preparative
      purposes.

PMID- 16580679
TI  - Effect of Campoletis sonorensis ichnovirus cys-motif proteins on Heliothis
      virescens larval development.
AB  - Polydnaviruses are obligate symbionts of some parasitic hymenopteran wasps
      responsible for modifying the physiology of their host lepidopteran larvae to
      benefit the endoparasite. Injection of Campoletis sonorensis ichnovirus (CsIV)
      into Heliothis virescens larvae alters larval growth, development and immunity
      but genes responsible for alterations of host physiology are not well described.
      Recent studies of polydnavirus genomes establish that these genomes encode
      families of related genes expressed in parasitized larvae. Here we evaluate five
      members of the CsIV cys-motif gene family for their ability to inhibit growth and
      development of lepidopteran larvae. To study the function of cys-motif proteins,
      recombinant proteins were produced from baculovirus expression vectors and
      injected or fed to H. virescens larvae in diet. rVHv1.1 was identified as the
      most potent protein tested causing a significant reduction in growth of H.
      virescens and Spodoptera exigua larvae. H. virescens larvae ingesting this
      protein also exhibited delayed development, reductions in pupation and increased
      mortality. Increased mortality was associated with chronic sub-lethal baculovirus
      infections. Taken together, these data indicate that the cys-motif proteins have
      pleiotropic effects on lepidopteran physiology affecting both development and
      immunity.

PMID- 16580680
TI  - Tandemization endows bovine pancreatic ribonuclease with cytotoxic activity.
AB  - Due to their ability to degrade RNA, selected members of the bovine pancreatic
      ribonuclease A (RNase A) superfamily are potent cytotoxins. These cytotoxic
      ribonucleases enter the cytosol of target cells, where they degrade cellular RNA
      and cause cell death. The cytotoxic activity of most RNases, however, is
      abolished by the cytosolic ribonuclease inhibitor (RI). Consequently, the
      development of RNase derivatives with the ability to evade RI binding is a
      desirable goal. In this study, tandem enzymes consisting of two RNase A units
      that are bound covalently via a peptide linker were generated by gene
      duplication. As deduced from the crystal structure of the RNase A.RI complex, one
      RNase A unit of the tandem enzyme can still be bound by RI. The other unit,
      however, should remain unbound because of steric hindrance. This free RNase A
      unit is expected to maintain its activity and to act as a cytotoxic agent. The
      study of the influence of the linker sequence on the conformation and stability
      of these constructs revealed that tandemization has only minor effects on the
      activity and stability of the constructs in comparison to monomeric RNase A.
      Relative activity was decreased by 10-50% and the melting temperature was
      decreased by less than 2.5 K. Furthermore, the cytotoxic potency of the RNase A
      tandem enzymes was investigated. Despite an in vitro inhibition by RI,
      tandemization was found to endow RNase A with remarkable cytotoxic activity.
      While monomeric RNase A is not cytotoxic, IC(50) values of the RNase A tandem
      variants decreased to 70.3-12.9 microM. These findings might establish the
      development of a new class of chemotherapeutic agents based on pancreatic
      ribonucleases.

PMID- 16580681
TI  - Desulfovibrio desulfuricans G20 tetraheme cytochrome structure at 1.5 Angstrom
      and cytochrome interaction with metal complexes.
AB  - The structure of the type I tetraheme cytochrome c(3) from Desulfovibrio
      desulfuricans G20 was determined to 1.5 Angstrom by X-ray crystallography. In
      addition to the oxidized form, the structure of the molybdate-bound form of the
      protein was determined from oxidized crystals soaked in sodium molybdate. Only
      small structural shifts were obtained with metal binding, consistent with the
      remarkable structural stability of this protein. In vitro experiments with pure
      cytochrome showed that molybdate could oxidize the reduced cytochrome, although
      not as rapidly as U(VI) present as uranyl acetate. Alterations in the overall
      conformation and thermostability of the metal-oxidized protein were investigated
      by circular dichroism studies. Again, only small changes in protein structure
      were documented. The location of the molybdate ion near heme IV in the crystal
      structure suggested heme IV as the site of electron exit from the reduced
      cytochrome and implicated Lys14 and Lys56 in binding. Analysis of structurally
      conserved water molecules in type I cytochrome c(3) crystal structures identified
      interactions predicted to be important for protein stability and possibly for
      intramolecular electron transfer among heme molecules.

PMID- 16580682
TI  - Stm1p, a ribosome-associated protein, is important for protein synthesis in
      Saccharomyces cerevisiae under nutritional stress conditions.
AB  - Stm1p is a Saccharomyces cerevisiae protein that has been implicated in several
      biological processes, ranging from apoptosis to telomere biosynthesis. Likewise,
      Stm1p has been identified as a protein associated with supramolecular structures,
      including ribosomes and nuclear telomere cap complexes. Using a variety of
      biochemical methods, we found that the vast majority of cellular Stm1p is
      associated with free cytosolic 80S ribosomes and polysomes. In its association
      with ribosomes, Stm1p interacts in an equimolar complex with both ribosomal
      subunits and is not associated with mRNA. Functionally, targeted disruption of
      the STM1 gene results in rapamycin hypersensitivity and a defect in recovery
      following nitrogen starvation and replenishment. These effects coincide with
      severe polysome depletion and reduced total protein synthesis. Taken together,
      our data indicate that Stm1p plays a critical role in facilitating translation
      under nutrient stress conditions and suggest that Stm1p acts in concert with the
      target of rapamycin (TOR) signaling pathway.

PMID- 16580683
TI  - Kinetics and energetics of ligand binding determined by microcalorimetry:
      insights into active site mobility in a psychrophilic alpha-amylase.
AB  - A new microcalorimetric method for recording the kinetic parameters k(cat), K(m)
      and K(i) of alpha-amylases using polysaccharides and oligosaccharides as
      substrates is described. This method is based on the heat released by glycosidic
      bond hydrolysis. The method has been developed to study the active site
      properties of the cold-active alpha-amylase produced by an Antarctic
      psychrophilic bacterium in comparison with its closest structural homolog from
      pig pancreas. It is shown that the psychrophilic alpha-amylase is more active on
      large macromolecular substrates and that the higher rate constants k(cat) are
      gained at the expense of a lower affinity for the substrate. The active site is
      able to accommodate larger inhibitory complexes, resulting in a mixed-type
      inhibition of starch hydrolysis by maltose. A method for recording the binding
      enthalpies by isothermal titration calorimetry in a low-affinity system has been
      developed, allowing analysis of the energetics of weak ligand binding using the
      allosteric activator chloride. It is shown that the low affinity of the
      psychrophilic alpha-amylase for chloride is entropically driven. The high
      enthalpic and entropic contributions of activator binding suggest large
      structural fluctuations between the free and the bound states of the cold-active
      enzyme. The kinetic and thermodynamic data for the psychrophilic alpha-amylase
      indicate that the strictly conserved side-chains involved in substrate binding
      and catalysis possess an improved mobility, responsible for activity in the cold,
      and resulting from the disappearance of stabilizing interactions far from the
      active site.

PMID- 16580684
TI  - Stimulated expression of mRNAs in activated T cells depends on a functional CRM1
      nuclear export pathway.
AB  - In metazoans, the nuclear export of bulk mRNAs is mediated by the export receptor
      TAP, together with its binding partner p15. A number of viral mRNAs, including
      the unspliced and partially spliced mRNA species of the human immunodeficiency
      virus (HIV), however, use an alternative export route via the importin beta
      related export receptor CRM1. This raises the question of whether a subset of
      cellular mRNAs might be exported by CRM1 as well. To identify such mRNAs, we
      performed a systematic screen in different cell lines, using representational
      difference analyses of cDNA (cDNA-RDA). In HeLa and Cl-4 cells no cellular
      transcripts could be identified as exported via CRM1. In contrast, we found a
      number of CRM1-dependent mRNAs in Jurkat T cells, most of which are induced
      during a T cell response. One of the identified gene products, the dendritic cell
      marker CD83, was analyzed in detail. CD83 expression depends on a functional CRM1
      pathway in activated Jurkat T cells as well as in a heterologous expression
      system, independent of activation. Our results point to an important role of the
      CRM1-dependent export pathway for the expression of CD83 and other genes under
      conditions of T cell activation.

PMID- 16580685
TI  - Uncoupling of RNA binding and PKR kinase activation by viral inhibitor RNAs.
AB  - Protein kinase RNA-activated (PKR) is a serine/threonine kinase that contains an
      N-terminal RNA-binding domain and a C-terminal kinase domain. Upon binding double
      stranded RNA (dsRNA), PKR can become activated and phosphorylate cellular
      targets, such as eukaryotic translation initiation factor 2alpha (eIF-2alpha).
      Phosphorylation of eIF-2alpha results in attenuation of protein translation by
      the ribosome in either a general or an mRNA-specific manner. Therefore, the
      interaction between PKR and dsRNAs represents a crucial host cell defense
      mechanism against viral infection. Viruses can circumvent PKR function by
      transcription of virus-encoded dsRNA inhibitors that bind to and inactivate PKR.
      We present here a biophysical characterization of the interactions between human
      PKR and two viral inhibitor RNAs, EBER(I) (from Epstein-Barr virus) and VA(I)
      (from human adenovirus). Autophosphorylation assays confirmed that both EBER(I)
      and VA(I) are inhibitors of PKR activation, and profiled the kinetics of the
      inhibition. Binding affinities of dsRNAs to PKR double-stranded RNA-binding
      domains (dsRBDs) were determined by isothermal titration calorimetry and gel
      electrophoresis. A single stem-loop domain from each inhibitory RNA mediates the
      interaction with both dsRBDs of PKR. The binding sites on inhibitor RNAs and the
      dsRBDs of PKR have been mapped by NMR chemical shift perturbation experiments,
      which indicate that inhibitors of PKR employ similar surfaces of interaction as
      activators. Finally, we show that dsRNA binding and inactivation are non
      equivalent; regions other than the dsRBD stem-loops of inhibitory RNA are
      required for inhibition.

PMID- 16580686
TI  - Evidence supporting a cis-enediol-based mechanism for Pyrococcus furiosus
      phosphoglucose isomerase.
AB  - The enzymatic aldose ketose isomerisation of glucose and fructose sugars involves
      the transfer of a hydrogen between their C1 and C2 carbon atoms and, in
      principle, can proceed through either a direct hydride shift or via a cis-enediol
      intermediate. Pyrococcus furiosus phosphoglucose isomerase (PfPGI), an archaeal
      metalloenzyme, which catalyses the interconversion of glucose 6-phosphate and
      fructose 6-phosphate, has been suggested to operate via a hydride shift
      mechanism. In contrast, the structurally distinct PGIs of eukaryotic or bacterial
      origin are thought to catalyse isomerisation via a cis-enediol intermediate. We
      have shown by NMR that hydrogen exchange between substrate and solvent occurs
      during the reaction catalysed by PfPGI eliminating the possibility of a hydride
      shift-based mechanism. In addition, kinetic measurements on this enzyme have
      shown that 5-phospho-d-arabinonohydroxamate, a stable analogue of the putative
      cis-enediol intermediate, is the most potent inhibitor of the enzyme yet
      discovered. Furthermore, determination and analysis of crystal structures of
      PfPGI with bound zinc and the substrate F6P, and with a number of competitive
      inhibitors, and EPR analysis of the coordination of the metal ion within PfPGI,
      have suggested that a cis-enediol intermediate-based mechanism is used by PfPGI
      with Glu97 acting as the catalytic base responsible for isomerisation.

PMID- 16580687
TI  - Neurogenic factors in the impaired healing of diabetic foot ulcers.
AB  - BACKGROUND: We hypothesize that the reduced innervation of skin can be observed
      both in clinically neuropathic and non-neuropathic diabetic foot ulcers and can
      contribute to low inflammatory cell infiltration. MATERIALS AND METHODS: Twenty
      patients with type 2 diabetes and active foot ulcers, without clinical evidence
      of peripheral sensory neuropathy (n = 12) and with sensory neuropathy (n = 8)
      were involved in this study. Biopsies from ulcer margin were examined
      immunohistochemically. RESULTS: Studies revealed presence of protein gene product
      9.5 (PGP9.5)+ nerve endings only in reticular dermis in 3 of 12 non-neuropathic
      subjects, however, regenerating GAP-43+ endings were seen in dermis of almost all
      specimens. Lack of substance P+ nerve endings was characteristic for both groups.
      The reduced distribution of calcitonin gene-related peptide+ nerves in epidermis
      and dermis was seen mainly in neuropathic group. In neo-epidermis lack of nerve
      growth factor expression was observed in both groups, whereas neurotrophin 3
      immunostaining was characteristic for neuropathic specimens (P < 0.03).
      Expression of trkA and trkC receptors did not differ significantly between
      groups. Low inflammatory cell infiltration and moderate presence of fibroblasts
      was characteristic for all studied specimens. CONCLUSIONS: The observed reduction
      of foot skin innervation and neurogenic factors expression can be correlated with
      low inflammatory cell accumulation and subsequently leads to the observed
      chronicity of diabetic foot ulcer healing process in both neuropathic and non
      neuropathic patients.

PMID- 16580688
TI  - Comparison of combat and non-combat burns from ongoing U.S. military operations.
AB  - BACKGROUND: Military burns result from either combat or non-combat causes. We
      compared these etiologies from patients involved in ongoing conflicts to evaluate
      their impact and provide prevention recommendations. METHODS: All military
      patients with significant burns treated at the United States Army Institute of
      Surgical Research from April 2003 to May 2005 were reviewed. Injuries were
      categorized as having resulted from combat or non-combat causes. Demographics,
      burn severity and pattern, mortality, and early outcomes were compared. RESULTS:
      There were 273 burn patients seen with 63% injured in combat. A high early rate
      of non-combat injuries was noted. Feedback on non-combat burn prevention was
      provided to the combat theater, and the incidence of non-combat burns decreased.
      Mean age and time from injury to admission did not differ. The majority of combat
      injuries resulted from explosive device detonation. Waste burning, ammunition
      handling, and gasoline caused most non-combat injuries. Combat casualties had
      more associated and inhalation injuries and greater full-thickness burn size;
      total body surface area burned was equivalent. The hands and the face were the
      most frequently burned body areas. Mortality was 5% in combat and 2% in non
      combat patients. The majority of survivors in both groups returned to military
      duty. CONCLUSIONS: The disparity in full-thickness burn size and incidence of
      inhalation and associated injuries resulted from differing mechanisms of injury,
      with explosions and penetrating trauma more common in combat wounds. Despite the
      severity of combat burns, mortality was low and outcomes generally good. Non
      combat burns are preventable and have decreased in incidence.

PMID- 16580689
TI  - Expression and regulation of AT1 receptor in rat lung microvascular endothelial
      cell.
AB  - BACKGROUND: The renin-angiotensin system is thought to be involved in the
      development and progression of vascular endothelium inflammation, thereby
      contributing to vascular endothelium injury. To clarify the role of angiotensin
      II (Ang II) in rat pulmonary microvascular endothelial cells (RPMVECs), we
      examined the expression and functional significance of angiotensin II (Ang II)
      receptors in normal and lipopolysacchride (LPS) treated RPMVECs. METHODS: The
      expressions of Ang II type 1(AT(1)) and Ang II type 2 (AT(2)) receptors in
      cultured RPMVECs were identified by the reverse transcription-polymerase chain
      reaction (RT-PCR) technique, Western blot and (125)I-labeled [Sar(1),Ile(8)] Ang
      II binding assays. The RPMVECs were treated with LPS (0.1-100 microg/ml) and Ang
      II (10(-8)-10(-5) M) for 24 h, respectively. Next, RPMVECs were treated with 10
      microg/ml LPS or 10(-7) M Ang II for various times (3, 6, 12, and 24 h). The mRNA
      and protein levels of, AT(1) and AT(2) receptors, were evaluated at 3, 6, 12, and
      24 h, respectively. RESULTS: The presence of specific Ang II binding sites in
      RPMVECs was found by Ang II saturated assays. RT-PCR revealed that only the AT(1)
      receptor mRNA is presented in RPMVECs. Western blot analysis of the RPMVECs
      protein extracts showed only one prominent band of the protein at approximately
      41 KDa when probed with anti-AT(1) antibody and anti-AT(2) antibody. No AT(2)
      receptor mRNA and protein was detected. LPS treated cells resulted in an increase
      in the mRNA and protein levels of AT(1) receptor, whereas, Ang II treated cells
      showed a decrease in the mRNA and protein levels of AT(1) receptor. CONCLUSIONS:
      We found that primary cultured RPMVECs expressed only AT(1) receptor, but not
      AT(2) receptor. LPS up-regulated the transcriptional and post-transcriptional
      expression of AT(1) receptor in RPMVECS; in contrast, Ang II treatment caused a
      reduction in the mRNA and protein of AT(1) receptor in a time-dependent manner.

PMID- 16580690
TI  - Activation of the melanocortin-4 receptor mobilizes intracellular free calcium in
      immortalized hypothalamic neurons.
AB  - BACKGROUND: At least 4% of childhood obesity is due to mutations in the
      hypothalamic melanocortin-4 receptor. The melanocortin-4 receptor, a seven
      transmembrane G-protein-coupled receptor, is important in the regulation of
      feeding behavior and body weight. The specific pathways of intracellular
      signaling remain in investigative stages. To further understand its function, we
      hypothesized that the melanocortin-4 receptor activates the Galphaq/phospholipase
      C signaling pathway, resulting in alterations of cytoplasmic calcium in
      immortalized hypothalamic (GT1-1) neurons. MATERIALS AND METHODS: Changes in
      intracellular calcium were measured after loading GT1-1 cells with fura-2-AM.
      Cells were treated with NDP-alphaMSH, an alpha-melanocortin stimulating hormone
      analogue, and intracellular calcium changes were recorded. Cells treated with NDP
      alpha-MSH were also treated with the melanocortin-4 receptor antagonist, SHU
      9119. To assess the specific G-protein subunit involved, GT1-1 neurons were
      treated with the phospholipase C inhibitor U73122 and its inactive analogue,
      U73433. Experiments were also performed after inhibition of IP3 receptors with 2
      aminoethoxydiphenylborate (2APB). Additional experiments were conducted in a
      calcium-depleted buffer environment. Data were analyzed by ANOVA with statistical
      significance of P < 0.05. RESULTS: Agonist treatment (0.01-1000 nm) of GT1-1
      neurons resulted in dose-dependent increases in intracellular calcium. SHU-9119
      (0.01-1000 nm) abolished the calcium response. Treatment with U73122 (10 microm)
      attenuated the calcium response, while U73433 (10 microm) had minimal effect.
      2APB (200 microm) inhibited the calcium transient, and the use of calcium-free
      buffer did not affect the amplitude of the calcium spike. CONCLUSIONS: Our study
      demonstrates that, upon agonist binding, the melanocortin-4 receptor mediates
      increases in intracellular calcium through the Galphaq-protein/phospholipase C
      dependent signaling pathway. Understanding the physiological importance of
      calcium signaling by the melanocortin-4 receptor may be important for future
      development of therapeutic targets.

PMID- 16580691
TI  - 3,3'-diindolylmethane and paclitaxel act synergistically to promote apoptosis in
      HER2/Neu human breast cancer cells.
AB  - BACKGROUND: HER2/neu positive breast tumors are difficult to treat. About 25 to
      30% of invasive breast tumors overexpress the HER2/neu oncogene. These tumors are
      aggressive and become resistant to chemotherapeutic drugs. 3'3'-diindolylmethane
      (DIM), the active metabolite of indole-3-carbinol, a naturally occurring compound
      found in cruciferous vegetables, has been found to have anti-cancer properties in
      both humans and animals. DIM has been shown to induce cell cycle arrest and
      apoptosis in animal breast cancer models. Because HER2/neu overexpression confers
      resistance to paclitaxel, and DIM has anti-tumor effects, we hypothesized that
      DIM will enhance the cytotoxic effects of paclitaxel, a common taxane drug, on
      human Her2/neu breast cancer cells by potentiating its effect on cell cycle and
      stimulating apoptosis. METHODS: The MDA-MB-435eB1 human Her2/neu breast cancer
      cells were treated with varying concentrations of DIM and paclitaxel. The cells
      were analyzed at different time points (24, 48, and 72 h). Proliferation was
      measured by a commercial cell proliferation assay (Promega Procheck Assay). Cell
      cycle analysis and apoptosis were determined by flow cytometry. Western blot
      analysis was performed on to determine the effect of DIM and/or paclitaxel on the
      proteins involved in apoptosis, and epidermal growth factor-induced activation of
      HER2/neu and ERK1/2 signaling proteins. RESULTS: Both DIM and paclitaxel
      exhibited time and concentration dependent inhibition of cell proliferation.
      TUNEL assay indicated that the combination also increased the number of apoptotic
      cells more than either agent alone. The presence of cleaved poly (ADP-Ribose)
      polymerase (PARP) significantly increased in the combination treatment, whereas
      Bcl-2 is decreased. DIM alone decreased the activation of the Her2/neu receptor;
      the combination decreased the activation of ERK1/ERK2. CONCLUSIONS: DIM in
      combination with paclitaxel synergistically inhibits growth of Her2/neu human
      breast cancer cells through G2M phase cell-cycle arrest and induction of
      apoptosis/necrosis. The Her2/neu receptor and its downstream signaling protein
      ERK1/2 appear to be involved in DIM's affect on cell growth and differentiation,
      whereas apoptosis appears to be mediated through the mitochondrial pathway (Bcl
      2/PARP). It appears DIM, a naturally occurring, nontoxic compound, may be a
      beneficial addition to a traditional (taxane-based) chemotherapy regimen.

PMID- 16580692
TI  - A surgical skills elective can improve student confidence prior to internship.
AB  - BACKGROUND: A focused surgical resident readiness curriculum for senior medical
      students can improve confidence in surgical skills compared to current surgical
      interns. MATERIALS AND METHODS: A 3-week surgical skills lab elective enrolled
      senior medical students applying to surgical residency programs, with the purpose
      of improving surgical skills and easing anxiety prior to surgical internship.
      Students were surveyed before and after the elective regarding their confidence
      in performing 21 skills covered by the curriculum. A similar confidence survey
      was administered to the incoming surgical intern class. Interns were also
      surveyed regarding prior skills lab instruction during medical school.
      Statistical analyses included Student's paired t-test and two-way analysis of
      variance. RESULTS: Six medical students and 23 interns were surveyed. All medical
      students significantly improved their confidence by the end of the resident
      readiness curriculum (P = 0.0004). Although students initially had lower
      confidence than surgical interns in performing surgical skills and in their
      knowledge of anatomy prior to the course, their confidence after the course was
      significantly higher than that of the incoming surgical interns (P = 0.035).
      Surgical interns with prior skills lab experience in their medical school
      reported higher confidence than those who did not have a skills lab experience (P
      = 0.019). Among all subgroups, medical students with skills lab experience had
      the highest confidence score, followed by interns with previous skills lab
      experience, then by interns with no previous skills lab experience, and last, by
      medical student with no skills lab experience. CONCLUSION: Surgical interns often
      feel unprepared to perform skills necessary for residency. A focused skills lab
      elective during medical school can bridge the gap and improve confidence prior to
      internship.

PMID- 16580693
TI  - Non-invasive assessment of the gracilis muscle by means of surface
      electromyography electrode arrays.
AB  - PURPOSE: The purpose of the study was the non-invasive investigation of the
      innervation zone (IZ) location of the gracilis muscle of both thighs by means of
      surface electromyography (EMG). MATERIALS AND METHODS: Multichannel EMG signals
      were detected by means of a flexible array of 16 equally spaced silver bar
      electrodes. Tests were performed on both gracilis muscles on 15 subjects. Motor
      unit (MU) action potentials were visually identified and extracted. The locations
      of the IZs of the recognized MUs were statistically analyzed to find significant
      differences between the subjects and between the right and left muscle of each
      subject. RESULTS AND CONCLUSIONS: A statistically significant difference was
      found between the gracilis IZ position in the two sides, with more proximal IZs
      on the left side. This difference suggests a possible role of surface EMG in
      preoperative evaluation of patients prepared for the dynamic graciloplasty
      procedure. This test would provide an objective criterion for the choice of the
      gracilis muscle to be transposed with the highest probability of success.

PMID- 16580694
TI  - An easy-to-use microwave hyperthermia system combined with spatially resolved MR
      temperature maps: phantom and animal studies.
AB  - BACKGROUND: Hyperthermia has been used in multimodal cancer treatments, and in
      randomized, controlled studies, hyperthermia is an effective cancer therapy. For
      clinical accuracy and safety, however, temperature monitoring during treatment is
      essential. We aimed to develop a convenient microwave hyperthermia system
      combined with spatially resolved real-time temperature monitoring to improve its
      efficacy and safety. MATERIALS AND METHODS: Using an MR-compatible irradiation
      type microwave applicator, agar phantoms, thigh muscles of rabbit, and
      subcutaneous VX2 tumors of rabbit were heated in combination with noninvasive MR
      temperature maps. For MR temperature calculation, a proton resonance frequency
      method was used. After determination of temperature coefficients and evaluation
      of the precision in MR thermometry, distribution of microwave heating over time
      was examined for each substance. RESULTS: The temperature coefficients of
      phantoms, rabbit muscles, and VX2 tumors were -0.00977, -0.00976, and -0.01027
      ppm/ degrees C, respectively. The 95% limits of agreement of MR and fluoroptic
      thermometry in the three subjects were +0.318/-0.339 degrees C, +0.693/-0.661
      degrees C, and +0.564/-0.526 degrees C, respectively. Concerning VX2 tumor, the
      average tumor temperature was 42.60 +/- 0.14 degrees C and the surface of skin
      was 43.27 +/- 0.45 degrees C in the 60-min experimental period. CONCLUSIONS: With
      this easy-to-use microwave hyperthermia system, effective hyperthermia was
      accomplished in phantoms and living animals in combination with MR temperature
      maps.

PMID- 16580695
TI  - Embolic internal auditory artery infarction from vertebral artery dissection.
AB  - A 51-year-old man developed sudden vertigo, right hearing loss and dysphagia.
      Examination revealed right Horner syndrome, spontaneous torsional-horizontal
      nystagmus, right central type facial palsy, dysarthria, reduced soft palate
      elevation without gag reflex, left hypesthesia, right dysmetria and imbalance.
      Audiometry and bithermal caloric tests documented right sensorineural hearing
      loss and canal paresis. Brain MRI and cerebral angiography documented right
      lateral medullary infarction from vertebral artery dissection, without
      involvement of other parts of the brainstem supplied by the anterior inferior
      cerebellar artery (AICA). This case suggests artery-to-artery embolism as a
      possible mechanism of isolated vertigo or hearing loss from labyrinthine
      infarction.

PMID- 16580696
TI  - Conjugate eye movements and gamma power modulation of the EEG in persistent
      vegetative state.
AB  - BACKGROUND: Power in the gamma band EEG increases during saccades in normal
      subjects. OBJECTIVE: To develop a potential method to quantify signs of cortical
      responsiveness in persistent vegetative state (PVS) we quantified gamma range EEG
      in association with conjugate slow ballistic eye movements (SBEM). METHODS: The
      EEG and the simultaneous electro-oculogram were recorded in 14 (8F/6M) PVS
      patients. Clinical scoring was based on the Glasgow Coma Scale (GCS) and Coma
      Rating Scale (CRS). The Wavelet Transform, followed by Hilbert transform was
      applied to the EEG and gamma power distribution was quantified relative to the
      timing of an eye movement. We correlated the clinical and the neurophysiological
      measures. RESULTS: Gamma activity was present in all PVS patients. Its power was
      modulated in association with eye movements only in less severely affected
      patients, with minimum power prior to, and maximum power during the eye movement.
      In severely affected patients there was no evidence of a temporal relationship
      between gamma power and the phase of the eye movement. CONCLUSIONS: Detecting
      changes in the time course of gamma power in relation to conjugate ballistic eye
      movements provides a quantitative neurophysiological method for prospective
      longitudinal studies to explore if the preservation of this CNS function relates
      to the potential for recovery in PVS patients.

PMID- 16580697
TI  - Waning of maternal immunity and the impact of diseases: the example of
      myxomatosis in natural rabbit populations.
AB  - Myxomatosis is a leporipoxvirus that infects the european rabbit, inducing a high
      mortality rate. Observations lead us to hypothesize that a rabbit carrying
      maternal antibodies (or having recovered) can be infected (or re-infected) upon
      being exposed (or re-exposed) to the virus. Infection will lead to mild disease,
      boosting host immune protection. Using a modelling approach we show that this
      phenomenon may lead to a difference of impact of myxomatosis according to its
      transmission rate. Young are exposed when they still carry maternal antibodies
      and develop a mild disease in high transmission populations. Our results show
      that the impact of myxomatosis is generally higher in epidemic situations
      compared to populations where the virus circulates all the year. As a
      consequence, waning of acquired immunity and the continuous supply of newborn
      along the year may reduce the impact of the disease.

PMID- 16580698
TI  - An antioxidant treatment potentially protects myocardial energy metabolism by
      regulating uncoupling protein 2 expression in a chronic beta-adrenergic
      stimulation rat model.
AB  - Excessive beta-adrenergic stimulation causes cardiac toxicity, which also
      contributes to cardiac oxidative stress. Although uncoupling protein 2 (UCP2), a
      member of the mitochondrial inner membrane carrier family, can regulate energy
      efficiency and oxidative stress in mitochondria, little data exist regarding
      interactions between UCP2 expression and beta-adrenergic stimulation induced
      cardiac oxidative damage. We investigated whether chronic beta-adrenergic
      stimulation induces myocardial energy metabolism abnormality via oxidative
      stress, including any role of UCP2. We also examined whether 3-methyl-1-phenyl-2
      pyrazolin-5-one (MIC-186; edaravone), a potent free radical scavenger, has
      cardioprotective effects against beta-adrenergic stimulation. Male Sprague-Dawley
      rats received isoproterenol (1.2 mg/kg/day) subcutaneously or/and edaravone (30
      mg/kg/day) orally. Isoproterenol increased the heart/body weight ratio,
      accompanied by an increase in the level of myocardial thiobarbituric acid
      reactive substances (TBARS) and a decreased phosphocreatine (PCr) to adenosine
      triphosphate (ATP) ratio. Isoproterenol also markedly increased expressions of
      UCP2 mRNA (1.74 fold vs. non-isoproterenol) and protein (1.93 fold vs. non
      isoproterenol). Edaravone had no apparent effect in hypertrophic responses, but
      significantly prevented both increases in TBARS and decreases in the PCr/ATP
      ratio. Edaravone also prevented increases in UCP2 mRNA (0.76 fold vs.
      isoproterenol) and protein (0.62 fold vs. isoproterenol) expressions against
      isoproterenol administration. Our results suggest that chronic beta-adrenergic
      stimulation induces myocardial energy inefficiency via excessive oxidative
      stress. The antioxidant effect of edaravone has potential to improve energy
      metabolism abnormalities against beta-adrenergic stimulation. Adequate regulation
      of UCP2 expression through artificial reduction of oxidative stress may play an
      important role in protection of the myocardial energy metabolism.

PMID- 16580699
TI  - A polymorphism of the methionine synthase reductase gene increases chromosomal
      damage in peripheral lymphocytes in smokers.
AB  - The cytogenetic effects of cigarette smoke has been evaluated as one of many
      potential confounders in a large number of biomonitoring studies of
      occupationally or environmentally exposed populations and control subjects.
      Despite the well-known presence of carcinogens in the cigarette smoke, the
      results in the scientific literature linking smoking habits to micronuclei (MN)
      frequency, one of the cytogenetic markers, are rather controversial. Here, we
      investigated the relationships among MN frequency, smoking habits and five folate
      metabolic enzyme gene polymorphisms (MTHFR C677T and A1298C, MTR A2756G, MTRR
      A66G and TYMS 3'UTR) in 132 healthy Japanese men who were non-habitual drinkers.
      In never- and former-smokers, no statistically significant differences in the
      mean MN frequencies were observed according to the five folate metabolic enzyme
      gene polymorphisms. In current-smokers, however, subjects with the AA genotype
      for MTRR had a significantly higher mean MN frequency than the AG genotypes for
      MTRR (p<0.05). Furthermore, among subjects with the AA genotype for MTRR, current
      smokers were found to have a significantly higher mean MN frequency than never-
      and former-smokers (p<0.05). To further characterize this association, we
      stratified the smoking status into five groups: non-smokers (never-smokers and
      former-smokers), 1-10 cigarettes/day, 11-20 cigarettes/day, 21-30 cigarettes/day
      and >or=31 cigarettes/day. There was an overall trend for the mean MN frequency
      in subjects with the MTRR AA genotype to increase as the number of cigarettes
      smoked per day increased (p<0.01, Jonckheere-Terpstra test). The results of our
      preliminary study suggest that the MTRR AA genotype acts to increase the MN
      frequency resulting from cigarette smoking. Therefore, studies on human
      genotoxicity based on cytogenetic markers of MN should take into account both the
      MTRR polymorphism and the potential confounding effect of smoking, although these
      preliminary findings need to be validated in larger populations because of the
      relatively small sample size.

PMID- 16580700
TI  - Visual search deficits in Parkinson's disease are attenuated by bottom-up target
      salience and top-down information.
AB  - Patients with Parkinson's disease (PD), a degenerative disorder primarily
      affecting the nigrostriatal dopamine system, exhibit deficits in selecting task
      relevant stimuli in the presence of irrelevant stimuli, such as in visual search
      tasks. However, results from previous studies suggest that these deficits may
      vary as a function of whether selection must rely primarily on the "bottom-up"
      salience of the target relative to background stimuli, or whether "top-down"
      information about the identity of the target is available to bias selection. In
      the present study, moderate-to-severe medicated PD patients and age-matched
      controls were tested on six visual search tasks that systematically varied the
      relationship between bottom-up target salience (feature search, noisy feature
      search, conjunction search) and top-down target knowledge (Target Known versus
      Target Unknown). Comparison of slope and intercepts of the RT x set size function
      provided information about the efficiency of search and non-search (e.g.,
      decision, response) components, respectively. Patients exhibited higher
      intercepts than controls as bottom-up target salience decreased, however these
      deficits were disproportionately larger under Target Unknown compared to Target
      Known conditions. Slope differences between PD and controls were limited to the
      Target Unknown Conjunction condition, where patients exhibited a shallower slope
      in the target absent condition, indicating that they terminated search earlier.
      These results suggest that under conditions of high background noise, medicated
      PD patients were primarily impaired in decision and/or response processes
      downstream from the target search itself, and that the deficit was attenuated
      when top-down information was available to guide selection of the target signal.

PMID- 16580702
TI  - Tyrosinemia produced by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3
      dione (NTBC) in experimental animals and its relationship to corneal injury.
AB  - 2-(2-Nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) is a potent
      inhibitor of rat liver 4-hydroxyphenylpyruvate dioxygenase (HPPD) leading to
      tyrosinemia and corneal opacity. We examined the effect of NTBC on the extent of
      tyrosinemia and production of corneal lesions in the beagle dog, rabbit and
      rhesus monkey, as part of safety evaluation on this drug. A single oral dose of
      10 mg NTBC/kg to beagle dogs or rabbits increased the concentration of tyrosine
      in plasma and aqueous humour of the eye, the tyrosinemia being both time- and
      dose-dependent. Hepatic HPPD was markedly inhibited with little effect on the
      activity of tyrosine aminotransferase (TAT) and homogentisic acid oxidase at the
      time of peak plasma tyrosine. Daily oral administration of NTBC to beagle dogs at
      0.1, 0.5, 1.5 and 5 mg/kg/day produced corneal opacities with an incidence of 34%
      following 11 weeks of dosing, which reversed upon withdrawal of the drug.
      Tyrosine in plasma and aqueous humour was increased at all dose levels, 18 weeks
      after dosing. In contrast, daily oral administration of NTBC to rabbits for 6
      weeks and rhesus monkeys for 12 weeks at 10 mg/kg/day produced no evidence of
      corneal opacities although tyrosine values were markedly increased. Our studies
      have shown that NTBC is a potent inhibitor of rabbit, beagle dog and by inference
      rhesus monkey liver HPPD producing a marked tyrosinemia in all species studied,
      while only beagle dogs show corneal lesions. The production of corneal lesions in
      experimental animals exposed to NTBC does not appear to be simply related to the
      concentration of tyrosine in ocular fluid, other as yet unidentified factors
      appear to be necessary to trigger tissue injury.

PMID- 16580703
TI  - CD28 in thymocyte development and peripheral T cell activation in mice exposed to
      suspended particulate matter.
AB  - The CD28:B7 signaling pathway is very important for the activity of mature
      peripheral T lymphocytes and thymocyte development. The proper development of
      thymocytes into mature single positive CD4+and CD8+ T cells is crucial for almost
      all immune functions. In naturally occurring conditions, T cells maturation in
      the thymus is influenced by environmental agents. The expression of CD28 and the
      distribution of CD28(low/high) thymocytes have been examined at various stages of
      thymocyte development in BALB/c mice exposed to air-suspended particulate matter
      (ASM). Acute exposure to ASM resulted in the decrease of CD28 expression in the
      total thymocyte population. The increase of the percentage of CD28(low) and the
      decrease of CD28(high) thymocytes were observed, which may account for the
      acceleration of thymocyte development under the conditions of elevated risk
      resulting from the exposure of animals to environmental xenobiotics. ASM exposure
      resulted in the increase of the level of proliferation of lymph node T cells
      induced by anti-CD3 and anti-CD28 monoclonal antibodies activation despite normal
      expression of CD28 molecule. In contrast, the level of proliferation of spleen T
      cells was lowered or normal dependently of the concentration of stimuli used for
      activation. Results of these studies demonstrate that acute exposure of mice to
      ASM can result in the progression of two contrasting processes in the immune
      system: upregulation of thymocyte development, which contributes to the
      maintenance of peripheral T cell pool, and over-activation of lymph node
      lymphocytes, which may lead to uncontrolled immunostimulation.

PMID- 16580701
TI  - Development of cognitive control and executive functions from 4 to 13 years:
      evidence from manipulations of memory, inhibition, and task switching.
AB  - Predictions concerning development, interrelations, and possible independence of
      working memory, inhibition, and cognitive flexibility were tested in 325
      participants (roughly 30 per age from 4 to 13 years and young adults; 50%
      female). All were tested on the same computerized battery, designed to manipulate
      memory and inhibition independently and together, in steady state (single-task
      blocks) and during task-switching, and to be appropriate over the lifespan and
      for neuroimaging (fMRI). This is one of the first studies, in children or adults,
      to explore: (a) how memory requirements interact with spatial compatibility and
      (b) spatial incompatibility effects both with stimulus-specific rules (Simon
      task) and with higher-level, conceptual rules. Even the youngest children could
      hold information in mind, inhibit a dominant response, and combine those as long
      as the inhibition required was steady-state and the rules remained constant.
      Cognitive flexibility (switching between rules), even with memory demands
      minimized, showed a longer developmental progression, with 13-year-olds still not
      at adult levels. Effects elicited only in Mixed blocks with adults were found in
      young children even in single-task blocks; while young children could exercise
      inhibition in steady state it exacted a cost not seen in adults, who (unlike
      young children) seemed to re-set their default response when inhibition of the
      same tendency was required throughout a block. The costs associated with
      manipulations of inhibition were greater in young children while the costs
      associated with increasing memory demands were greater in adults. Effects seen
      only in RT in adults were seen primarily in accuracy in young children. Adults
      slowed down on difficult trials to preserve accuracy; but the youngest children
      were impulsive; their RT remained more constant but at an accuracy cost on
      difficult trials. Contrary to our predictions of independence between memory and
      inhibition, when matched for difficulty RT correlations between these were as
      high as 0.8, although accuracy correlations were less than half that. Spatial
      incompatibility effects and global and local switch costs were evident in
      children and adults, differing only in size. Other effects (e.g., asymmetric
      switch costs and the interaction of switching rules and switching response-sites)
      differed fundamentally over age.

PMID- 16580704
TI  - Collision efficiency distribution of a bacterial suspension flowing through
      porous media and implications for field-scale transport.
AB  - The collision efficiency (alpha) distribution of a bacterial population was
      determined using multiple packed-bed columns of varying lengths and analyzing the
      bacteria clean-bed breakthrough concentrations using a distributed colloid
      filtration theory. This technique allows the alpha distribution to be determined
      independently from other effects that can cause non-exponential deposition,
      including detachment and blocking. It was found that multiple probability density
      functions (PDF's) could accurately replicate the experimental data. Regardless of
      which PDF was used, a distributed alpha resulted in significantly greater
      predicted field-scale transport than when using a single alpha. However, there
      were wide variations in the predicted field-scale transport between the different
      distributions, suggesting that lab-scale experiments may not be readily utilized
      to determine the specific PDF that best represents alpha at the field scale.
      Finally, blocking was observed in the column effluent curves, underscoring the
      fact that if non-clean-bed processes occur then an approach such as that utilized
      in the current study may be used to separate the non-clean-bed and clean-bed
      processes when determining the collision efficiency distribution.

PMID- 16580705
TI  - Genetic polymorphisms in CYP1A1 and GSTM1 predispose humans to PCBs/PCDFs-induced
      skin lesions.
AB  - INTRODUCTION: Polychlorinated biphenyls (PCBs) and dibenzofurans (PCDFs) are
      ubiquitous persistent pollutants in humans. Whether people with different
      genotypes are with different susceptibility to these chemicals are unknown. In a
      group of people highly exposed to PCBs/PCDFs, we tested the hypothesis that
      genotypic polymorphisms affected susceptibility for development of skin
      manifestations. METHODS: In 1979, approximately 2000 people in central Taiwan
      ingested cooking oil contaminated with PCBs/PCDFs. Skin disorder such as
      chloracne, abnormal nail, hyperkeratosis and skin allergy were found in
      PCBs/PCDFs exposed group. We recruited exposed and community background exposure
      subjects for blood testing and telephone-interview. Single nucleotide
      polymorphisms, AhR Arg554Lys, CYP1A1 Ile462Val, CYP1A1 T6235C, and GSTM1/T1
      deletion, were determined. Occurrence of skin manifestations was compared among
      people with different genotypes while stratified by PCB exposure levels by
      logistic regression. RESULTS: Data on exposure, medical history, and genotypes
      were obtained from 393 exposed and 181 background exposure groups. Skin
      manifestations including chloracne, allergy, abnormal nail, and hyperkeratosis
      were more prevalent in exposed people in a dose-related manner. Among highly
      exposed individuals, combined CYP1A1-MspI mutant genotype and GSTM1-null genotype
      were associated with increased risk of chloracne (odds ratio 2.8, 95% confidence
      interval 1.1-7.6). Among intermediately exposed individuals, GSTM1 null genotype
      was associated with skin allergy. AhR Arg554Lys genotype and GSTT1 null genotype
      were not related to susceptibility to skin manifestations in PCB/PCDF-exposed
      population. CONCLUSION: CYP1A1 and GSTM1 genotypic polymorphisms might be related
      to the susceptibility to PCB/PCDF-induced skin manifestations.

PMID- 16580706
TI  - Alkaline hydrothermal treatment of brominated high impact polystyrene (HIPS-Br)
      for bromine and bromine-free plastic recovery.
AB  - A method to recover both Br and Br-free plastic from brominated flame retardant
      high impact polystyrene (HIPS-Br) was proposed. HIPS-Br containing 15% Br was
      treated in autoclave at 280 degrees C using water or KOH solution of various
      amounts and concentrations. Hydrothermal treatment (30 ml water) leads to 90%
      debromination of 1g HIPS-Br but plastic is strongly degraded and could not be
      recovered. Alkaline hydrothermal treatment (45 ml or 60 ml KOH 1M) showed similar
      debromination for up to 12 g HIPS-Br and plastic was recovered as pellets with
      molecular weight distribution close to that of the initial material.
      Debromination occurs at melt plastic/KOH solution interface when liquid/vapour
      equilibrium is attained inside autoclave (280 degrees C and 7 MPa in our
      experimental conditions) and depends on the plastic amount/KOH volume ratio. The
      antimony oxide synergist from HIPS-Br remains in recovered plastic during
      treatment. A pictorial imagination of the proposed debromination process is
      presented.

PMID- 16580707
TI  - Incorporating variations in pesticide catabolic activity into a GIS-based
      groundwater risk assessment.
AB  - The catabolic activity of incumbent microorganisms in soil samples of eleven
      dissimilar soil series was investigated, with respect to the herbicide
      isoproturon. Soils were collected from a 30x37 km area of river catchment to the
      north-west of London, England. Catabolic activity in each soil type during a 500
      h assay was determined by 14C-radiorespirometry. Results showed four soils that
      exhibited high levels of catabolic activity (33-44% mineralisation) while the
      remaining seven soils showed lower levels of catabolic activity (12-16%
      mineralisation). There was evidence to suggest that soils exhibiting high
      catabolic activity had low (<22%) clay content and tended towards lower organic
      carbon content (<2.7%), but that these higher levels of catabolic activity were
      also related to pre-exposure to isoproturon. The 14C-radiorespirometric results
      were used to produce a GIS layer representing levels of catabolic activity for
      the dissimilar soils across the study area. This layer was combined with other
      GIS layers relating to pesticide attenuation, including soil organic carbon
      content, depth to groundwater and hydrogeology, to produce a map showing risk of
      groundwater contamination by isoproturon. The output from this approach was
      compared with output from an attenuation-only approach and differences appraised.
      Inclusion of the catabolism layer resulted in a lowering of risk in the model in
      15% of the study area. Although there appears to be limited benefit in including
      pesticide catabolic activity in this regional-scale groundwater risk model, this
      type of addition could be useful in a site-specific risk assessment.

PMID- 16580708
TI  - A prediction method for radon in groundwater using GIS and multivariate
      statistics.
AB  - Radon (222Rn) in groundwater constitutes a source of natural radioactivity to
      indoor air. It is difficult to make predictions of radon levels in groundwater
      due to the heterogeneous distribution of uranium and radium, flow patterns and
      varying geochemical conditions. High radon concentrations in groundwater are not
      always associated with high uranium content in the bedrock, since groundwater
      with a high radon content has been found in regions with low to moderate uranium
      concentrations in the bedrock. This paper describes a methodology for predicting
      areas with high concentrations of 222Rn in groundwater on a general scale, within
      an area of approximately 185x145km2. The methodology is based on multivariate
      statistical analyses, including principal component analysis and regression
      analysis, and investigates the factors of geology, land use, topography and
      uranium (U) content in the bedrock. A statistical variable based method (the RV
      method) was used to estimate risk values related to different radon
      concentrations. The method was calibrated and tested on more than 4400 drilled
      wells in Stockholm County. The results showed that radon concentration was
      clearly correlated to bedrock type, well altitude and distance from fracture
      zones. The weighted index (risk value) estimated by the RV method provided a fair
      prediction of radon potential in groundwater on a general scale. Risk values
      obtained using the RV method were compared to radon measurements in 12 test areas
      (on a local scale, each of area 25x25km2) in Stockholm County and a high
      correlation (r=-0.87) was observed. The study showed that the occurrence and
      spread of radon in groundwater are guided by multiple factors, which can be used
      in a radon prediction method on a general scale. However, it does not provide any
      direct information on the geochemical and flow processes involved.

PMID- 16580709
TI  - Mercury content in commercial pelagic fish and its risk assessment in the Western
      Indian Ocean.
AB  - As top predators of pelagic food webs, large fish naturally bioaccumulate mercury
      (Hg). Determining Hg burdens in commercialized fish is essential considering the
      concern about effects of contaminants on human health and the legal thresholds
      that are therefore set for local consumption and/or exportation. Total Hg levels
      were measured in the muscular tissue of 183 fish of five commercially important
      species from the tropical zone of the Western Indian Ocean. All individuals were
      measured and sexed in order to study the impregnation of Hg with size and sex
      within each species. Values of Hg found in this part of the Indian Ocean were
      comparable to Hg in muscular tissue of the same species studied in other areas.
      The highest Hg levels were noted in Swordfish (Xiphias gladius) caught in waters
      surrounding Reunion Island (3.97+/-2.67 microg g(-1) dry weight). Following the
      Swordfish, in decreasing order of Hg content, were the Yellowfin Tuna (Thunnus
      albacares) and the Skipjack (Katsuwonus pelamis), then the Common Dolphinfish
      (Coryphaena hippurus) and the Wahoo (Acanthocybium solandri). In the North of the
      Mozambique Channel, Swordfish had higher Hg levels than Yellowfin Tunas, and
      Dolphinfish exhibited intermediate Hg levels. The size of a fish was a
      determining factor of its Hg burden, as was the species. Differences in size
      normalized Hg levels were observed between the two study zones for Swordfish and
      Common Dolphinfish. Sex, in contrast, did not influence Hg levels suggesting that
      females and males have similar feeding habits. The muscular Hg levels presented
      here suggest that consumers of fish originating from the Western Indian Ocean
      should limit themselves to one Swordfish based meal per week, or one fish meal a
      day if they choose to eat tuna or Common Dolphinfish.

PMID- 16580710
TI  - Willingness to pay for reducing fatal risk by improving air quality: a contingent
      valuation study in Chongqing, China.
AB  - In China, 76% of all energy comes from coal consumption, which is the major cause
      of air pollution. One of the major barriers to developing sound policies for
      controlling air pollution is the lack of information related to the value of the
      health consequences of air pollution. We conducted a willingness-to-pay (WTP)
      study using contingent valuation (CV) methods in Chongqing, China to estimate the
      economic value of saving one statistical life through improving air quality. A
      sample of 500residents was chosen based on multistage sampling methods. A face-to
      face household interview was conducted using a series of hypothetical, open-ended
      scenarios followed by bidding game questions designed to elicit the respondents'
      WTP for air pollution reduction. The Two-Part Model was used for estimations. The
      results show that 96% of respondents were able to express their WTP. Their mean
      annual income is $490. Their WTP to save one statistical life is $34,458.
      Marginal increases for saving one statistical life is $240 with 1year age
      increase, $14,434 with 100yuan monthly income increase, and $1590 with 1year
      education increase. Unlike developed country, clean air may still be considered
      as a "luxury" good in China based on the estimation of income elasticity.

PMID- 16580711
TI  - Differences in Mn uptake and subcellular distribution in different barley
      genotypes as a response to Cd toxicity.
AB  - A hydroponics experiment was carried out in greenhouse to study the genotypic
      differences in Mn uptake and subcellular distribution in response to Cd toxicity.
      Increased Cd level in medium caused a significant reduction in plant height and
      fresh weight, and ZAU3 and Wumaoliuling being the least and the most affected
      genotypes, respectively. There was a marked difference in proportion of Mn
      accumulation in different fractions relative to the total Mn amount in tissues
      among the 4 fractions, with the soluble fraction FIV showing the largest
      proportion in shoots, followed by organelle containing fraction (FIII), while
      cell wall (FI) and chloroplasts FII being the smallest. Meanwhile, Cd
      significantly increased FIII Mn accumulation proportion, but decreased FIV
      proportion, with significant genotypic difference of Wumaoliuling being the least
      increase in FIII and the greatest decrease in FIV among the 4 genotypes. In
      roots, the major pool of Mn content was FI, FIV, and FIII, and Cd induced no
      significant changes. Furthermore, Cd caused a significant reduction in
      subcellular Mn concentration of FI and FIV fractions in shoots and the 4
      fractions in roots, with more pronounced in Cd-sensitive cultivar Wumaoliuling in
      root FII, FIII and FIV, and shoot FI, FII, and FIII, while little difference in
      both Mn concentrations of root FI, and shoot FIV.

PMID- 16580712
TI  - Metastatic choriocarcinoma successfully treated with paclitaxel and carboplatin
      after interstitial lung disease induced by EMA-CO.
AB  - BACKGROUND: Well-established first-line chemotherapy (such as EMA-CO) is
      extraordinary active for gestational choriocarcinoma. However, it causes very
      serious situation once drug-induced acute interstitial lung disease occurs during
      the treatment. CASE: A 31-year-old Japanese woman with metastatic choriocarcinoma
      was treated with EMA-CO as an initial chemotherapy regimen for seven cycles. Her
      beta-hCG dropped from 13,087 ng/ml to 2.2 ng/ml. At 11 days after 7th cycle of
      EMA-CO treatment, however, she developed respiratory failure, and was diagnosed
      as having EMA-CO-induced interstitial lung disease with bilateral ground-glass
      opacity on CT scan, and the examination of the bronchoalveolar lavage fluid.
      After high-dose steroid therapy, symptoms and ground-glass opacity on CT scan
      were remarkably improved. She then commenced a regimen of carboplatin (AUC 5) and
      paclitaxel (180 mg/m2). After completing 8 cycles, her beta-hCG dropped to <0.2
      ng/ml. Three additional cycles were administered and the patient remained
      clinically free of disease, with normal beta-hCG levels for 11 months.
      CONCLUSIONS: Paclitaxel and carboplatin combination is active and appears to be a
      viable alternative to EMA-CO combination chemotherapy in metastatic
      choriocarcinoma even after EMA-CO-induced interstitial lung disease.

PMID- 16580713
TI  - Spontaneously hypertensive rats do not predict symptoms of attention-deficit
      hyperactivity disorder.
AB  - The validity of the Spontaneously Hypertensive rat (SHR) as a model for Attention
      Deficit Hyperactivity Disorder (ADHD) is explored by comparing the SHR with
      Wistar-Kyoto (WKY) and Wistar rats in a number of different tests. In the open
      field, SHR are hyperactive compared to both Wistar and WKY, but only at specific
      ages. At those ages, methylphenidate (1mg/kg) did not attenuate hyperactivity.
      Subsequently, a dose response study of methylphenidate (0.1-10mg/kg) was
      conducted in the Differential Reinforcement of Low-rate responding (DRL)-72s and
      five-choice serial reaction time tests (5-CSRTT). Compared to WKY but not Wistar
      rats, SHR performed worse on the DRL-72s. Performance was not improved by
      methylphenidate (0.1-1.0mg/kg). In the 5-CSRTT, attentional performance was
      similar for all rat strains, but Wistar rats made more impulsive responses than
      both the SHR and the WKY. Methylphenidate only attenuated impulsivity in Wistar
      rats. Because SHR do not consistently display symptoms of ADHD across the
      different tests, and methylphenidate effects were observed in both WKY and Wistar
      rats, but not in SHR, we conclude that SHR is not a representative animal model
      for ADHD.

PMID- 16580714
TI  - Socioeconomic inequality in cigarette smoking: trends by gender, age, and
      socioeconomic position in South Korea, 1989-2003.
AB  - OBJECTIVE: The aim of this study was to examine trends of socioeconomic
      differentials in smoking rates by gender, age, and socioeconomic position in
      South Korea. METHODS: We used data from five Social Statistical Surveys of Korea
      National Statistical Office from 1989 to 2003. This study included 344,969 men
      and women aged 20 or over. Socioeconomic position indicators were education and
      occupation. RESULTS: Age-standardized smoking rates decreased in all age groups
      of men and women aged 45+ between 1989 and 2003, while smoking rates among women
      aged 20-44 did not decrease. Education was inversely associated with smoking in
      both genders. Those with manual occupations had greater smoking rates than those
      who performed non-manual labor. Based on the relative index of inequality,
      unfavorable inequality trends toward low education were detected in both genders
      aged 20-44. However, these trends were not found at ages 45-64. For occupational
      class, the relative inequality in smoking measured by odds ratios remained stable
      among men and women between 1995 and 2003. CONCLUSIONS: Continuous and
      progressive anti-smoking policy measures should be directed toward South Korean
      men whose smoking rates are still high. Policy efforts to reduce socioeconomic
      inequality in smoking, especially among young adult men and women, should be
      exercised. In addition, additional anti-smoking policy measures toward young
      women's smoking habits need to be developed in South Korea.

PMID- 16580715
TI  - Embryo development of prepubertal goat oocytes fertilised by intracytoplasmic
      sperm injection (ICSI) according to oocyte diameter.
AB  - The aim of this study was to evaluate embryo development of prepubertal goat
      oocytes fertilised by ICSI according to their diameter. Three experiments were
      carried out to achieve this objective. In all experiments, oocytes were matured
      in TCM199 supplemented with hormones, cysteamine and serum for 27 h at 38.5
      degrees C. In Experiment 1, we studied the nuclear stage of goat zygotes produced
      by conventional ICSI and IVF using 20 nM ionomycin plus 10 microM heparin as
      sperm treatment. A group of Sham-injected oocytes was used as control. Results
      showed differences in the percentage of 2 PN (zygotes with male and female
      pronuclei) between ICSI, IVF and Sham (40.9, 26.6 and 3.0%, respectively;
      P<0.05). In Experiment 2, we evaluated the embryo development of prepubertal goat
      oocytes produced by ICSI and IVF after 192 h of culture in SOF medium. The
      percentage of morulae plus blastocysts obtained was higher in the ICSI than in
      the IVF group (13.4 and 5.1%, respectively; P<0.05). In Experiment 3, IVM-oocytes
      were classified in four groups depending on their diameter (Group A: <110 microm;
      Group B: 110-125 microm; Group C: 125-135 microm; Group D: >135 microm),
      fertilised by ICSI and cultured for 192 h. Results showed a positive correlation
      between oocyte diameter and embryo development (morulae+blastocysts: Group A: 0%;
      Group B: 6.2%; Group C: 46.4% and Group D: 33.3%). In conclusion, sperm treatment
      with ionomycin plus heparin using the conventional ICSI protocol improved
      fertilisation rates in comparison to IVF. Oocytes smaller than 125 microm were
      unable to develop up to blastocyst stage.

PMID- 16580716
TI  - Responses of canine oocytes to in vitro maturation and in vitro fertilization
      outcome.
AB  - The potential benefits of assisted reproduction techniques, such as in vitro
      maturation (IVM) and in vitro fertilization (IVF) in canids, are linked to the
      protection and saving of species threatened by extinction due to worldwide
      habitat destruction and pollution. In both domestic and wild species, these
      technologies will form the basis for the next leap in reproductive performance by
      improving fertility rates in valuable middle-aged females, by improving pregnancy
      rate in infertile or sub-fertile populations and by rescuing biological material
      to replenish populations of endangered species. In vitro techniques are supposed
      to answer the reproductive questions of canids, to introduce new methods for
      contraception and to compete with artificial insemination (AI) as the major or
      predominant method of embryo production, oocyte- and embryo cryopreservation and
      cloning. The causes affecting in vitro meiosis of dog oocytes are likely to be
      diverse. Incomplete understanding of the events associated with oocyte
      developmental competence are imputed to species reproductive physiology, medium
      composition and source of ovarian oocyte population used for in vitro maturation.
      This review addresses some issues on the current state of in vitro maturation and
      in vitro fertilization of canine oocytes.

PMID- 16580717
TI  - Development of a new rapid measurement technique for fish embryo membrane
      permeability studies using impedance spectroscopy.
AB  - Information on fish embryo membrane permeability is vital in their
      cryopreservation. Whilst conventional volumetric measurement based assessment
      methods have been widely used in fish embryo membrane permeability studies, they
      are lengthy and reduce the capacity for multi-embryo measurement during an
      experimental run. A new rapid 'real-time' measurement technique is required to
      determine membrane permeability during cryoprotectant treatment. In this study,
      zebrafish (Danio rerio) embryo membrane permeability to cryoprotectants was
      investigated using impedance spectroscopy. An embryo holding cell, capable of
      holding up to 10 zebrafish embryos was built incorporating the original system
      electrods for measuring the impedance spectra. The holding cell was tested with
      deionised water and a series of KCl solutions with known conductance values to
      confirm the performance of the modified system. Untreated intact embryos were
      then tested to optimise the loading capacity and sensitivity of the system. To
      study the impedance changes of zebrafish embryos during cryoprotectant exposure,
      three, six or nine embryos at 50% epiboly stage were loaded into the holding cell
      in egg water, which was then removed and replaced by 0.5, 1.0, 2.0 or 3M methanol
      or dimethyl sulfoxide (DMSO). The impedance changes of the loaded embryos in
      different cryoprotectant solutions were monitored over 30 min at 22 degrees C,
      immediately following embryo exposure to cryoprotectants, at the frequency range
      of 10-10(6)Hz. The impedance changes of the embryos in egg water were used as
      controls. Results from this study showed that the optimum embryo loading level
      was six embryos per cell for each experimental run. The optimum frequency was
      identified at 10(3.14) or 1,380 Hz which provided good sensitivity and
      reproducibility. Significant impedance changes were detected after embryos were
      exposed to different concentrations of cryoprotectants. The results agreed well
      with those obtained from conventional volumetric based studies.

PMID- 16580718
TI  - Effects of breed on kinetics of ovine FSH and ovarian response in superovulated
      sheep.
AB  - Embryo production is a useful tool for ex situ conservation of endangered species
      and breeds, despite a high variability in the ovarian response to superovulatory
      treatments. The current study evaluated the incidence and mechanisms of genetic
      factors in such variability, by determining the pharmacokinetics and
      pharmacodynamics of a standard treatment with ovine FSH (oFSH) in two endangered
      Spanish sheep breeds (Rubia del Molar, R, and Negra de Colmenar, N) in comparison
      to Manchega ewes (M, control group). In the first experiment, pharmacokinetics of
      an i.m. single dose of 1.32 mg of oFSH was evaluated in seven animals of each
      breed. Plasma FSH concentrations reached their maximum at 4h post-administration
      in all the ewes, but several of the kinetic parameters (plasma FSH concentration
      at 4h post-administration, maximum plasma FSH concentration, C(max), and both the
      area under the plasma concentration-time curve extrapolated to the infinite,
      AUC(inf), and to the last moment of sampling, AUC(last)) were higher in the N
      group. In the second trial, 10 animals of each breed were superovulated using
      eight decreasing doses of oFSH (3 x 1.32 mg, 2 x 1.10 mg, and 3 x 0.88 mg). The R
      group, when compared to N and M, showed both a higher number of corpora lutea
      (13.7+/-0.6 versus 10.0+/-0.4 in N and 9.8+/-0.6 in M, P<0.05 for both) and
      embryos (7.9+/-0.8 versus 4.3+/-0.4 in N, P<0.05, and 6.7+/-0.5 in M, n.s.).
      Evaluation of pharmacokinetic and dynamic parameters showed that, although there
      was a trend for a higher hormone availability in R sheep, mean FSH plasma
      concentrations were similar between breeds (0.54+/-0.08 ng/ml for R, 0.45+/-0.05
      ng/ml for N and 0.35+/-0.05 ng/ml for M). However, differences were found in the
      number of preovulatory follicles growing in response to the FSH treatment between
      R (24.4+/-2.2), M (18.9+/-1.5, n.s.) and N sheep (14.1+/-1.4; P<0.01). Thus,
      differences in embryo yields between breeds would be related to differences in
      the pattern of follicular growth in response to FSH treatment.

PMID- 16580719
TI  - Electrochemical characterization of cobalt-based alloys using the mini-cell
      system.
AB  - OBJECTIVES: The aim of this work was to investigate the electrochemical behavior
      of cobalt-based alloys of different compositions using the mini-cell system (MCS)
      and to test the sensitivity of this technique in the detection of variations in
      the electrochemical behavior caused by the different compositions of cobalt-based
      alloys. METHODS: The electrochemical measurements were performed on two cobalt
      based alloys, having a small content of gold (Barlight and Gold Core); one cobalt
      platinum-ruthenium alloy (Porta Smart) and one classical Co-based alloy
      (Wironit), in two different electrolytes, 1% NaCl and phosphate buffered solution
      (PBS). RESULTS: Based on I versus E curves, enhanced pitting corrosion capability
      was observed for the cobalt-based alloys, especially for those with lower
      chromium content and with the addition of a small amount of gold. The alloying of
      Co with Pt and Ru (Porta Smart), and the standard Co-based alloy do not show any
      critical instability; in contrast, a small addition of Au enhanced the pitting
      corrosion activity and reduced the corrosion stability. For higher alloy
      stability, a minimum 30% atomic ratio of chromium in the alloy composition is
      necessary. Furthermore, it was shown that MCS has sensitivity for the qualitative
      comparison of the alloys as well as in the electrochemical characterization of
      each alloy. SIGNIFICANCE: Electrochemical measurements are essential to assess
      the quality of an alloy. MCS might help in understanding the role the elements
      play in the electrochemical behavior of the alloys and at the same time
      contribute to the selection of the alloys in terms of their quality, even before
      more complex tests in vitro or in vivo are applied, and might reduce the costs
      for materials research.

PMID- 16580720
TI  - Partial purification and MALDI-TOF MS analysis of UN1, a tumor antigen membrane
      glycoprotein.
AB  - UN1 is a membrane glycoprotein that is expressed in immature human thymocytes, a
      subpopulation of peripheral T lymphocytes, the HPB acute lymphoblastic leukemia
      (ALL) T-cell line and fetal thymus. We previously reported the isolation of a
      monoclonal antibody (UN1 mAb) recognizing the UN1 protein that was classified as
      "unclustered" at the 5th and 6th International Workshop and Conference on Human
      Leukocyte Differentiation Antigens. UN1 was highly expressed in breast cancer
      tissues and was undetected in non-proliferative lesions and in normal breast
      tissues, indicating a role for UN1 in the development of a tumorigenic phenotype
      of breast cancer cells. In this study, we report a partial purification of the
      UN1 protein from HPB-ALL T cells by anion-exchange chromatography followed by
      immunoprecipitation with the UN1 mAb and MALDI-TOF MS analysis. This analysis
      should assist in identifying the amino acid sequence of UN1.

PMID- 16580721
TI  - The clinical impact of physical-chemical characteristics of different hyaluronic
      acids as a treatment for osteoarthritis.

PMID- 16580722
TI  - Analysis of disulphide bond connectivity patterns in protein tertiary structure.
AB  - The analysis of disulphide bond containing proteins in the Protein Data Bank
      (PDB) revealed that out of 27,209 protein structures analyzed, 12,832 proteins
      contain at least one intra-chain disulphide bond and 811 proteins contain at
      least one inter-chain disulphide bond. The intra-chain disulphide bond containing
      proteins can be grouped into 256 categories based on the number of disulphide
      bonds and the disulphide bond connectivity patterns (DBCPs) that were generated
      according to the position of half-cystine residues along the protein chain. The
      PDB entries corresponding to these 256 categories represent 509 unique SCOP
      superfamilies. A simple web-based computational tool is made freely available at
      the website that allows flexible queries to be made on the database in order to
      retrieve useful information on the disulphide bond containing proteins in the
      PDB. The database is useful to identify the different SCOP superfamilies
      associated with a particular disulphide bond connectivity pattern or vice versa.
      It is possible to define a query based either on a single field or a combination
      of the following fields, i.e., PDB code, protein name, SCOP superfamily name,
      number of disulphide bonds, disulphide bond connectivity pattern and the number
      of amino acid residues in a protein chain and retrieve information that match the
      criterion. Thereby, the database may be useful to select suitable protein
      structural templates in order to model the more distantly related protein
      homologs/analogs using the comparative modeling methods.

PMID- 16580723
TI  - Challenging protein purification from anammox bacteria.
AB  - The anaerobic ammonium oxidation (anammox) is a fascinating microbial pathway
      contributing to the global biogeochemical nitrogen cycle. The anammox pathway of
      nitrogen conversion can only be elucidated after the responsible proteins have
      been purified and characterised. The anammox bacteria have a complex cell
      envelope consisting of protein and lipopolysaccharide and they grow in dense cell
      aggregates. Preparing cell extract and purifying proteins from the cell
      aggregates is hampered by the extracellular polymeric material and by gel
      formation. It was demonstrated that protein-protein (i.e. disulfide formation) as
      well as protein-polysaccharide interaction caused this gel formation in extracts.
      Cell extract gelled upon freezing/thawing and boiling. Additionally, proteins
      aggregated on various chromatography media upon concentration and during
      desalting. The polysaccharides clogged the matrix of chromatographic materials
      and the pores of ultrafiltration membranes. The precipitation of proteins and
      polysaccharides caused very low resolution and streaking on SDS- and two
      dimensional polyacrylamide gels. The present work describes the potential causes
      for gel formation in anammox cell extracts. Optimized protocols for sample
      preparation for polyacrylamide gel electrophoresis and ion exchange
      chromatography are presented. High-resolution gel electrophoresis of the cell
      extract was achieved after clarification from polymeric substances with
      denaturating phenol extraction and the purification of a 10 kDa cytochrome c is
      presented as an example.

PMID- 16580724
TI  - Effects of mechanical wounding on Carica papaya cysteine endopeptidases
      accumulation and activity.
AB  - The mechanical wounding impact on the Carica papaya latex protein pattern was
      investigated by analyzing three latexes. A first one commercially available, a
      second harvested from unripe but fully grown fruits, both obtained from regularly
      tapped fruits. A third one was collected from similar fruits but wounded for the
      first time. The results demonstrated both quantitative and qualitative changes in
      the protein content and in the enzymatic activity. Repeated wounding results in
      either, accumulation or activation (or both of them) of papain, chymopapain and
      caricain. Furthermore, new cysteine protease activity was found to transiently
      accumulate in the latex collected from newly wounded fruits. The possible
      implication of this enzymatic material in the papaya cysteine endopeptidases pro
      forms activation is discussed.

PMID- 16580725
TI  - Purification and characterization of hydrosoluble components from the sap of
      Chinese lacquer tree Rhus vernicifera.
AB  - Continuous gradient elution chromatography (CGEC) was employed to purify and
      separate enzymes and polysaccharides from the sap of Rhus vernicifera Chinese
      lacquer tree. There are three different molecules with laccase enzyme activity.
      Two are enzymes of each other (L1, and L2), whereas the third (RL) is an entirely
      separate entity. Two polysaccharides (GP1 and GP2) were also found. The Rhus
      laccase (RL), and isoenzymes L1 and L2, have peak molecular masses of 109,100,
      120,000, 103,000 respectively; each has four copper atoms per molecule, and the
      pI values were 8.2, 8.6, and 9.1, respectively. The structure of the laccases was
      studied by Fourier-transform infrared (FT-IR) and Matrix-assisted laser
      desorption/ionization time-of flight (MALDI-TOF) mass spectrometry. The typical
      amide I (1646cm(-1)) and amide II (1545cm(-1)) bands were observed. The results
      from MALDI-TOF were similar to those from CGEC, but the molecular mass from the
      MALDI-TOF was significantly different from that obtained from sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

PMID- 16580727
TI  - Uptake and decarboxylation of L-3,4-dihydroxyphenylalanine in cultured monkey
      placenta amniotic epithelial cells.
AB  - In this study we tested the ability of monkey amniotic epithelial cells (MAEC) to
      take up and decarboxylate l-3,4-dihydroxyphenylalanine (l-DOPA) by incubating the
      cells in buffer containing l-DOPA under different experimental conditions
      followed by assaying cellular dopamine (DA) content using high performance liquid
      chromatography with electrochemical detection. Cellular contents of DA were
      significantly increased in a time- and l-DOPA-concentration-dependent manner,
      suggesting the uptake of l-DOPA by MAEC and indicating the presence of aromatic l
      amino acid decarboxylase (AADC). This was confirmed by the decreased DA content
      in the presence of benserazide, an AADC inhibitor. Neither d-DOPA nor DA uptake
      blockers such as mazindol and GBR 12935 significantly affected l-DOPA uptake and
      hence DA levels. Further, synthesis of DA from l-DOPA was decreased in the
      presence of the amino acids tyrosine, phenylalanine and tryptophan, whereas the
      amino acids glycine and proline were without any significant effect. These
      findings suggest that MAEC have the capacity to selectively take up and
      decarboxylate l-DOPA with subsequent production of DA.

PMID- 16580726
TI  - Paradoxical discrepancy between the serum level and the placental intensity of
      PP5/TFPI-2 in preeclampsia and/or intrauterine growth restriction: possible
      interaction and correlation with glypican-3 hold the key.
AB  - There have been controversies whether maternal serum placental protein 5
      (PP5)/tissue factor pathway inhibitor (TFPI)-2 is increased in the patients with
      preeclampsia and/or intrauterine growth restriction (IUGR). Here, we have
      estimated the serum PP5/TFPI-2 in these patients by a sandwich enzyme-linked
      immunosorbent assay with a newly developed monoclonal antibody, coupled with
      placental immunohistochemical studies of their placentae with semiquantitative
      scoring. Serum PP5/TFPI-2 level was significantly elevated only in the patients
      with preeclampsia alone (p=0.033), while PP5/TFPI-2 was detected significantly
      less intensely in the placentae of the same patients (p=0.035) in
      immunohistochemistry, as compared to Controls. A proteoglycan present on the
      placental villous surface, glypican-3, showed the same pattern of staining as
      PP5/TFPI-2, and there was a positive correlation (C.I.=0.506, p=0.004) between
      the immunohistochemical scores for these. Further experiments using HepG2 cells
      transfected with PP5/TFPI-2 suggested that glypican-3 could anchor PP5/TFPI-2 on
      the placental villi. A possibility that a decrease in glypican-3 in the placenta
      increases the outflow of PP5/TFPI-2, which in turn increases its serum level, was
      proposed. Preeclampsia and IUGR, often regarded to have the same pathological
      basis in common, showed distinct distributions of PP5/TFPI-2, which could be a
      clue to elucidate the pathogenesis of preeclampsia and IUGR.

PMID- 16580728
TI  - Neuropathological, neurogenetic and neuroimaging evidence for white matter
      pathology in schizophrenia.
AB  - A wide range of neuropathological abnormalities have been detected in
      schizophrenia sufferers, and emerging evidence points to neural substrates of
      connectivity as having a key role in the development of disease. This article
      reviews the available evidence for white matter pathology in schizophrenia, and
      examines its possible role as a substrate of impaired connectivity.
      Neuropathological data is suggestive of abnormalities in glial structure and
      function, and myelinated structures have also been implicated. A number of
      studies, particularly using gene array technology, are pointing towards
      significant disruption in expression of myelination genes. Magnetic resonance
      imaging has tended to focus on, and detect, more grey than white matter
      abnormalities, although non-volumetric techniques are suggestive of changes in
      the microstructure of white matter in schizophrenia. Myelinated structures are an
      attractive candidate for an anatomical substrate for disconnectivity, and may act
      synergistically with synaptic changes to result in functional disconnectivity
      although the relationship between white and grey matter changes in the illness
      remains unclear.

PMID- 16580729
TI  - Effects of NMDA receptor inhibition by phencyclidine on the neuronal
      differentiation of PC12 cells.
AB  - Phencyclidine (PCP) is a non-competitive N-methyl-d-aspartate (NMDA) receptor
      antagonist and exposing the developing brain to PCP has been shown to cause
      deficits in neurobehavioral functions. In the present study we tested the effects
      of PCP, as an NMDA receptor inhibitor, on the neuronal differentiation and
      biogenic amines levels including norepinephrine (NE), epinephrine, dopamine, 3,4
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT),
      and 5-hydroxyindole-3-acetic acid (5-HIAA) in the rat pheochromocytoma (PC12)
      cells. After PC12 cells were differentiated with nerve growth factor (NGF) in the
      presence of PCP, NMDA binding kinetics, biogenic amines analysis and NMDA
      receptor protein expression assay were conducted. The results showed that NMDA
      receptor binding activities were significantly increased after differentiated
      with NGF in PC12 cells. B(max) values were increased in differentiated cells by
      four-folds, whereas K(d) values were not changed. All of biogenic amines were
      significantly increased in differentiated cells. On the other hand, PCP at 50 and
      100 microM inhibited neuronal differentiation in a dose-dependent manner in NGF
      stimulated PC12 cells without affecting cell viability. PCP treatment during
      differentiation significantly reduced NMDA binding activity and biogenic amine
      levels. Western blotting analysis revealed that NMDA receptor protein expression
      was significantly higher in NGF-differentiated cells and PCP treatment decreased
      the expression of NMDA receptor proteins. These results indicate that NMDA
      receptor functions and monoaminergic nervous systems are significantly stimulated
      during NGF-induced differentiation. PCP suppresses neuronal outgrowth and hampers
      neuronal functions possibly by inhibiting NMDA receptor functions and biogenic
      amine production, implying the suppressive effects of PCP exposure on neuronal
      developments.

PMID- 16580730
TI  - Experimental infection of ground squirrels (Citellus pygmaeus Pallas) with
      Yersinia pestis during hibernation.
AB  - OBJECTIVES: In this study, we investigated the capability remain latent infection
      of Yersinia pestis in ground squirrels (Citellus pygmaeus Pallas) after their
      challenge with Y. pestis over the hibernation period. METHODS: Ground squirrels
      were challenged with Y. pestis by either subcutaneous injection (n=106 animals)
      or by infected fleabite (n=33 rodents). The development of plague in hibernating
      rodents was monitored daily for the signs of illness; if the animal died, the
      spleen, liver, lung, lymph nodes, bone brain, kidney and blood were taken for
      bacteriological and histopathologic examinations. RESULTS: In 35.8% (38 of 106)
      of the ground squirrels the plague has been developed after the challenge with Y.
      pestis via the s.c. injection within eight months, i.e. winter, spring and summer
      the periods of the observation. Overall, in 48.5% (16 of 33) of the animals the
      plague was developed during three months after the challenge with infected
      fleabite. The infection with Y. pestis was confirmed by bacteriologically and
      histopathological changes, e.g. pneumonia and necrosis in tissues of the ground
      squirrels. CONCLUSIONS: The results support the hypothesis that Y. pestis can
      remain latent in winter-sleeping ground squirrels during their hibernation and
      this phenomenon plays an important role in the epizootics of rodents after
      reawakening in the spring.

PMID- 16580731
TI  - Characterization of chromatin samples in the presence of Drosophila embryo
      extract by quantitative agarose gel electrophoresis.
AB  - Recent studies have focused attention on chromatin as both a negative and
      positive regulator of specific nuclear events. The vast majority of this research
      has been centered on chromatin remodeling and histone post-translational
      modifications over the regulatory regions of specific genes. However, due the
      technical difficulties of such studies, the contribution of the higher-order
      structure of chromatin on the regulation of gene expression has not been as
      thoroughly investigated and the majority of the initial studies have used
      biophysical methods or microscopy. Until recent technical developments, the main
      hindrance for these biophysical investigations of chromatin has been an almost
      absolute requirement for large amounts of highly purified material. The
      development of an agarose gel electrophoresis method (quantitative agarose gel
      electrophoresis), initially designed for the analysis of the three-dimensional
      structure of purified and in vivo-assembled chromatin over a promoter region, has
      been expanded to include studies of chromatin in the presence of a Drosophila
      crude extract. The technique presented in the study reported here will help in
      paving the way for subsequent analyses of structural modifications of chromatin
      that are linked with the recruitment of various chromatin-associated factors
      present in the provided extract(s).

PMID- 16580733
TI  - Klusters, NeuroScope, NDManager: a free software suite for neurophysiological
      data processing and visualization.
AB  - Recent technological advances now allow for simultaneous recording of large
      populations of anatomically distributed neurons in behaving animals. The free
      software package described here was designed to help neurophysiologists process
      and view recorded data in an efficient and user-friendly manner. This package
      consists of several well-integrated applications, including NeuroScope
      (http://neuroscope.sourceforce.net), an advanced viewer for electrophysiological
      and behavioral data with limited editing capabilities, Klusters
      (http://klusters.sourceforge.net), a graphical cluster cutting application for
      manual and semi-automatic spike sorting, NDManager (GPL,see
      http://www.gnu.org/licenses/gpl.html), an experimental parameter and data
      processing manager. All of these programs are distributed under the GNU General
      Public License (GPL, see ), which gives its users legal permission to copy,
      distribute and/or modify the software. Also included are extensive user manuals
      and sample data, as well as source code and documentation.

PMID- 16580732
TI  - 3D volume reconstruction of a mouse brain from histological sections using warp
      filtering.
AB  - Sectioning tissues for optical microscopy often introduces upon the resulting
      sections distortions that make 3D reconstruction difficult. Here we present an
      automatic method for producing a smooth 3D volume from distorted 2D sections in
      the absence of any undistorted references. The method is based on pairwise
      elastic image warps between successive tissue sections, which can be computed by
      2D image registration. Using a Gaussian filter, an average warp is computed for
      each section from the pairwise warps in a group of its neighboring sections. The
      average warps deform each section to match its neighboring sections, thus
      creating a smooth volume where corresponding features on successive sections lie
      close to each other. The proposed method can be used with any existing 2D image
      registration method for 3D reconstruction. In particular, we present a novel
      image warping algorithm based on dynamic programming that extends Dynamic Time
      Warping in 1D speech recognition to compute pairwise warps between high
      resolution 2D images. The warping algorithm efficiently computes a restricted
      class of 2D local deformations that are characteristic between successive tissue
      sections. Finally, a validation framework is proposed and applied to evaluate the
      quality of reconstruction using both real sections and a synthetic volume.

PMID- 16580734
TI  - State-dependent implicit learning deficit in schizophrenia: evidence from 20
      month follow-up.
AB  - Previous research has confirmed stable explicit memory deficits in schizophrenia
      across disease states. However, little is known about the implicit learning
      capabilities of individuals with schizophrenia across the course of illness. The
      current study assessed procedural learning in 19 schizophrenia subjects (DSM-IV
      criteria) and 19 matched controls using the Serial Reaction-Time Task (SRTT). The
      severity of negative, positive and disorganized symptoms was assessed using the
      Scales for the Assessment of Positive and Negative Symptoms. A sub-sample of 11
      schizophrenia subjects and 11 controls was reassessed 20 months later when
      symptoms in the schizophrenia subjects had largely remitted. Schizophrenia
      subjects were severely impaired on sequence-specific procedural learning during
      an acute episode. This deficit could not be explained by a general memory or
      processing speed impairment. Impaired implicit learning scores were significantly
      related to higher ratings of disorganized symptoms. However, 20 months later,
      when acute symptoms had remitted, the performance of the schizophrenia subjects
      on procedural learning had normalized. Our findings might share a conceptual
      overlap with previous reports of a reduced ability of schizophrenia subjects
      during an acute episode to adapt ongoing perceptual and behavioral programs to
      previously experienced regularities in their environment.

PMID- 16580735
TI  - The immunological synapse: kinases in T cell signalling as potential drug
      targets.
AB  - This international workshop on key signalling molecules in lymphocyte activation
      and immune regulation was held in Grossziethen, Germany from November 02-04, 2005
      and brought together molecular, cellular, and clinical immunologists whose common
      goal is to develop ways of manipulating the immune response in order to avert T
      cell effector functions that are of significant relevance for pathogenesis in
      different diseases, including dermatological (psoriasis, atopic dermatitis and
      allergic contact allergy) and other indications (e.g. asthma, rheumatoid
      arthritis, multiple sclerosis and transplant rejection).

PMID- 16580736
TI  - CD28 and ICOS: similar or separate costimulators of T cells?
AB  - Numerous studies have revealed that the B7.1/B7.2-CD28 and B7RP-1-ICOS (Inducible
      COStimulator) pathways provide crucial costimulatory signals to T cells. We have
      compared the contribution of these pathways during primary and effector
      responses, in vitro and in vivo, molecularly as well as functionally. This
      comparison between CD28 an ICOS after initiation of T cell activation
      demonstrates that both CD28 and ICOS function similarly during expansion,
      survival and differentiation of T cells and that both CD28 and ICOS are necessary
      for proper IgG responses. The major differences between CD28 and ICOS are
      differences in expression of both receptors and ligands, and the fact that CD28
      induces IL-2 production, whereas ICOS does not. In addition, ICOS is more potent
      in the induction of IL-10 production, a cytokine important for suppressive
      function of T regulatory cells. All data available at present indicate that both
      molecules are very suitable candidates for immunotherapy, each in their own
      unique way.

PMID- 16580737
TI  - Fusion protein of ATPase domain of Hsc70 with TRP2 acting as a tumor vaccine
      against B16 melanoma.
AB  - HSP70s are a family of ATP-dependent chaperones of relative molecular masses
      around 70kDa. Immunization of mice with HSP70 isolated from tumor tissues has
      been proved to elicit specific protective immunity against the original tumor.
      Recent researches have demonstrated that the ATPase domain of HSP70 and the tumor
      antigenic peptide that binds to Hsp70 were the crucial parts eliciting tumor
      specific immunity. These findings suggested that a recombinant protein expressed
      in Escherichia coli, comprising a covalently fused fragment of tumor rejection
      antigen to ATPase domain of HSP70, could be used as a tumor vaccine. However,
      high-level expressions of heterologous recombinant proteins in E. coli often lead
      to the formation of inclusion bodies, resulting in defects in solubility and
      bioactivity. In the present work, we found an approach to resolve these problems,
      focusing on a refolding procedure via gel-filtration chromatography for denatured
      inclusion body proteins. Here, we expressed, purified and refolded a fusion
      protein comprising murine heat shock cognate protein 70 (Hsc70) N-terminal ATPase
      domain (Hsc70NTD) and a portion of TRP2 (aa153-417) as a model protein. The
      refolding effectivities were assessed according to their ATPase activities, the
      vaccine function was assessed according to immunization effect in inducing
      antigen-specific CTLs and to in vivo tumor protection. The results showed that
      the fusion protein refolded via gel-filtration chromatography exhibited ATPase
      activity, succeeded in eliciting antigen-specific CTL in vivo and delayed tumor
      growth on tumor-bearing mice.

PMID- 16580738
TI  - Cytokine-mediated modulation of MMPs and TIMPs in multipotential neural precursor
      cells.
AB  - Recent studies have implicated the inflammatory process during experimental
      allergic encephalomyelitis (EAE) in triggering migration and differentiation of
      transplanted neural precursors cells (NPCs) into the inflamed white matter. The
      pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha and interferon (IFN)
      gamma are key factors in the pathogenesis of brain inflammation in EAE and were
      shown to enhance NPCs migration in vitro. As cell migration is dependent on
      extracellular matrix remodeling, involving proteolytic enzyme members of the
      matrix metalloproteinase (MMPs) family, we characterized the profile of
      expression of MMPs and their endogenous inhibitors (TIMPs) in rat NPCs, and
      evaluated the effects of TNF-alpha, IFN-gamma and IFN-beta, a clinically proven
      modulator of brain inflammation, on the expression of these molecules. Newborn
      rat striatal NPCs were expanded in spheres as nestin+, PSA-NCAM+ and NG2(-)
      cells, which can differentiate into astrocytes, oligodendrocytes and neurons.
      NPCs' gelatinase activities of MMP-2 and MMP-9, as determined by zymography, were
      increased by TNF-alpha, and to a lesser extent by IFN-gamma. Semi-quantitative RT
      PCR indicated that TNF-alpha also upregulated MMP-9 mRNA levels. IFN-beta
      suppressed the TNF-alpha-induced levels of secreted MMP-9 and MMP-2, while
      enhancing the expression of TIMP-1 and TIMP-2 mRNA. These results suggest that
      MMPs activity is induced in NPCs by pro-inflammatory cytokines to mobilize them
      for promoting reparative processes. IFN-beta, on the other hand, appears to have
      an anti-proteolytic influence that may attenuate such NPC-mediated repair
      processes.

PMID- 16580739
TI  - Cell survival matters: docosahexaenoic acid signaling, neuroprotection and
      photoreceptors.
AB  - Recent data have provided important clues about the molecular mechanisms
      underlying certain retinal degenerative diseases, including retinitis pigmentosa
      and age-related macular degeneration. Photoreceptor cell degeneration is a
      feature common to these diseases, and the death of these cells in many instances
      seems to involve the closely associated retinal pigment epithelial (RPE) cells.
      Under normal circumstances, both cell types are subject to potentially damaging
      stimuli (e.g. sunlight and high oxygen tension). However, the mechanism or
      mechanisms by which homeostasis is maintained in this part of the eye, which is
      crucial for sight, are an unsolved riddle. The omega-3 fatty acid family member
      docosahexaenoic acid (DHA), which is enriched in these cells, is the precursor of
      neuroprotectin D1 (NPD1). NPD1 inhibits oxidative-stress-mediated proinflammatory
      gene induction and apoptosis, and consequently promotes RPE cell survival. This
      enhanced understanding of the molecular basis of endogenous anti-inflammatory and
      neuroprotective signaling in the RPE presents an opportunity for the development
      of therapies for retinal degenerative diseases.

PMID- 16580740
TI  - Electrolytic lesions of a discrete area within the nucleus accumbens shell
      attenuate the long-term expression, but not early phase, of sensitization to
      cocaine.
AB  - Repeated exposure to cocaine leads to behavioral sensitization, which is the
      augmentation of the locomotor response to a subsequent exposure to the drug. The
      nucleus accumbens (NAc), a major termination site of dopaminergic neurons, is
      believed to be involved in behavioral sensitization and studies have demonstrated
      that the NAc shell can be split into five zones of analysis; the vertex, arch,
      cone, intermediate and ventrolateral zones [Todtenkopf MS, Stellar JR. Assessment
      of tyrosine hydroxylase immunoreactive innervation in five subregions of the
      nucleus accumbens shell in rats treated with repeated cocaine. Synapse
      2000;38:261-70]. Several reports show cocaine-induced c-fos expression
      particularly in the intermediate zone after 14, but not 2, drug-free days
      following repeated cocaine administration, suggesting that this region may be
      involved in sensitization and particularly in the later phase of expression,
      versus the earlier phase of sensitization. Bilateral electrolytic lesions of the
      intermediate zone were made in two groups of rats, which were then repeatedly
      exposed to cocaine (15 mg/kg, twice/day for 5 days). One group was subsequently
      given a single cocaine challenge injection (15 mg/kg) after 14 drug-free days,
      while the other group was challenged after only 2 drug-free days. Two sham
      surgery groups in which an electrode was lowered but no current was passed served
      as controls. Results show that lesioned animals as well as sham controls
      exhibited behavioral sensitization to the drug. However, following a 14-day drug
      free period, the lesioned animals showed significant reduction in sensitization,
      compared to sham controls. Together these findings suggest that the intermediate
      zone of the NAc shell is indeed involved in the expression phase of behavioral
      sensitization to cocaine.

PMID- 16580741
TI  - Differential social regulation of two pituitary gonadotropin-releasing hormone
      receptors.
AB  - In many vertebrates, social interactions regulate reproductive capacity by
      altering the activity of the hypothalamic-pituitary-gonadal (HPG) axis. To better
      understand the mechanisms underlying social regulation of reproduction, we
      investigated the relationship between social status and one main component of the
      HPG axis: expression levels of gonadotropin-releasing hormone receptor (GnRH-R).
      Social interactions dictate reproductive capacity in the cichlid fish
      Astatotilapia burtoni. Reproductively active territory holders suppress the HPG
      axis of non-territorial males through repeated aggressive encounters. To
      determine whether the expression of GnRH-R is socially regulated, we quantified
      mRNA levels of two GnRH-R variants in the pituitaries and brains of territorial
      (T) and non-territorial (NT) A. burtoni males. We found that T males had
      significantly higher levels of pituitary GnRH-R1 mRNA than NT males. In contrast,
      GnRH-R2 mRNA levels in the pituitary did not vary with social status. Pituitaries
      from both T and NT males expressed significantly higher mRNA levels of GnRH-R1
      than GnRH-R2. GnRH mRNA levels in the brain correlated positively with GnRH-R1
      mRNA levels in the pituitary but did not correlate with pituitary GnRH-R2.
      Measurements of GnRH-R1 and GnRH-R2 mRNA levels across the whole brain revealed
      no social status differences. These results show that, in addition to the known
      effects of social status on other levels of the HPG axis, GnRH receptor in the
      pituitary is also a target of social regulation.

PMID- 16580742
TI  - Enhanced context-dependency of object recognition in rats with hippocampal
      lesions.
AB  - Object recognition memory was assessed on a novel-object preference (NOP) task in
      rats with lesions of the hippocampal formation (HPC). The learning and test
      phases of NOP trials occurred in either the same context or in different
      contexts. When the learning and test contexts were the same, rats with HPC
      lesions performed like control rats, displaying a significant tendency to
      investigate a novel object more than a familiar sample object. When the test
      occurred in a context that was familiar but different from the learning context,
      performance was unaffected in control rats, but rats with HPC lesions no longer
      discriminated between the objects, and therefore showed no evidence of
      recognizing the sample object. When the test context was unfamiliar, novel-object
      preference in control rats was attenuated but still above chance levels, whereas
      rats with HPC lesions did not show a preference. The data suggest that the HPC is
      not critical for encoding or retrieving conjunctive representations of the
      context in which incidental learning occurs, whereas it plays an essential role
      in recognition of objects that are subsequently encountered in different
      contexts.

PMID- 16580743
TI  - Administration of raloxifene reduces sensorimotor and working memory deficits
      following traumatic brain injury.
AB  - Hormonal differences between males and females have surfaced as a crucial
      component in the search for effective treatments after experimental models of
      traumatic brain injury (TBI). Recent findings have shown that selective estrogen
      receptor modulators (SERMs) may have therapeutic benefit. The present study
      examined the effects of raloxifene, a SERM, on functional recovery after
      bilateral cortical contusion injury (bCCI) or sham procedure. Male rats received
      injections of raloxifene (3.0mg/kg, i.p.) or vehicle (1.0 ml/kg, i.p.) 15 min,
      24, 48, 72, and 96 h after bCCI or sham procedure. Rats were tested on both
      sensorimotor (bilateral tactile removal and locomotor placing tests) and
      cognitive tests (reference and working memory in the Morris water maze).
      Raloxifene-treated animals showed a significant reduction in the initial
      magnitude of the deficit and facilitated the rate of recovery for the bilateral
      tactile removal test, compared to vehicle-treated animals. The raloxifene-treated
      animals also showed a significant improvement in the acquisition of working
      memory compared to vehicle-treated animals. However, raloxifene did not
      significantly improve the acquisition of reference memory or locomotor placing
      ability. Raloxifene treatment also did not result in a significant reduction in
      the size of the lesion cavity. Thus, the task-dependent improvements seen
      following raloxifene treatment do not appear to be the result of cortical
      neuroprotection. However, these results suggest that raloxifene improves
      functional outcome following bCCI and may present an interesting avenue for
      future research.

PMID- 16580744
TI  - Preliminary study of responses in mussel (Mytilus edilus) exposed to bisphenol A,
      diallyl phthalate and tetrabromodiphenyl ether.
AB  - Environmental pollutants with hormonal activity including bisphenol, diallyl
      phtalate and tetrabromodiphenyl ether, have the potential to alter gonadal
      development and reproduction in aquatic wildlife. Little is known about the
      biological impact of environmentally relevant concentrations in mussels. To
      investigate some aspects of their potential estrogenic action, mussels were
      continuously exposed during 3 weeks. Gonadal development and vitellogenin like
      protein levels were examined. Bisphenol (50 microg/l) induced the expression of
      phospho-proteins in females and spawning in both sexes. Diallyl phthalate and
      tetrabromodiphenyl ether decreased phospho-protein levels in both sexes and
      induced spawning in males. Moreover, severe damaging effects on ovarian follicles
      and ovocytes were observed in both bisphenol A- and tetrabromodiphenyl ether
      exposed female mussels.

PMID- 16580748
TI  - Deciphering B-ZIP transcription factor interactions in vitro and in vivo.
AB  - Over the last 15 years, numerous studies have addressed the structural rules that
      regulate dimerization stability and dimerization specificity of the leucine
      zipper, a dimeric parallel coiled-coil domain that can either homodimerize or
      heterodimerize. Initially, these studies were performed with a limited set of B
      ZIP proteins, sequence-specific DNA binding proteins that dimerize using the
      leucine zipper domain to bind DNA. A global analysis of B-ZIP leucine zipper
      dimerization properties can be rationalized using a limited number of structural
      rules [J.R. Newman, A.E. Keating, Comprehensive identification of human bZIP
      interactions with coiled-coil arrays, Science 300 (2003) 2097-2101]. Today,
      however, access to the genomic sequences of many different organisms has made
      possible the annotation of all B-ZIP proteins from several species and has
      generated a bank of data that can be used to refine, and potentially expand,
      these rules. Already, a comparative analysis of the B-ZIP proteins from
      Arabidopsis thaliana and Homo sapiens has revealed that the same amino acids are
      used in different patterns to generate diverse B-ZIP dimerization patterns [C.D.
      Deppmann, A. Acharya, V. Rishi, B. Wobbes, S. Smeekens, E.J. Taparowsky, C.
      Vinson, Dimerization specificity of all 67 B-ZIP motifs in Arabidopsis thaliana:
      a comparison to Homo sapiens B-ZIP motifs, Nucleic Acids Res. 32 (2004) 3435
      3445]. The challenge ahead is to investigate the biological significance of
      different B-ZIP protein-protein interactions. Gaining insight at this level will
      rely on ongoing investigations to (a) define the role of target DNA on modulating
      B-ZIP dimerization partners, (b) characterize the B-ZIP transcriptome in various
      cells and tissues through mRNA microarray analysis, (c) identify the genomic
      localization of B-ZIP binding at a genomic level using the chromatin
      immunoprecipitation assay, and (d) develop more sophisticated imaging
      technologies to visualize dimer dynamics in single cells and whole organisms.
      Studies of B-ZIP family leucine zipper dimerization and the regulatory mechanisms
      that control their biological activities could serve as a paradigm for
      deciphering the biophysical and biological parameters governing other well
      characterized protein-protein interaction motifs. This review will focus on the
      dimerization specificity of coiled-coil proteins, particularly the human B-ZIP
      transcription family that consists of 53 proteins that use the leucine zipper
      coiled-coil as a dimerization motif.

PMID- 16580747
TI  - Impairment of lower jaw growth in developing zebrafish exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin and reduced hedgehog expression.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to cause a multitude of
      detrimental effects to developing zebrafish (Danio rerio). Previously, we
      demonstrated that jaw growth was impaired by TCDD exposure, but the exact
      mechanism underlying these malformations remained unknown. In the present study,
      we investigated the involvement of hedgehog genes and their downstream signaling
      in TCDD-mediated jaw malformation. We demonstrate that the developing lower jaw
      expresses sonic hedgehog a (shha), sonic hedgehog b (shhb) and their receptors,
      patched1 (ptc1) and patched2 (ptc2), as well as the downstream transcription
      factors, gli1 and gli2a. Loss of Hh signaling in mutants (sonic you) and larvae
      treated with a Hh inhibitor (cyclopamine), resulted in similar effects as those
      caused by TCDD. Moreover, TCDD exposure caused downregulation of shha and shhb in
      a manner dependent on aryl hydrocarbon receptor 2 (ahr2). Although this suggested
      an involvement of Hh signaling in TCDD-mediated impairment of jaw growth, we did
      not observe downregulation of ptc1 and ptc2, receptors dependent on Hh signaling.
      Furthermore, while the overall occurrence of apoptosis in the developing jaw was
      minimal, it was significantly increased in larvae treated with cyclopamine. In
      contrast, both TCDD and cyclopamine markedly reduced immunoreactivity against
      phosphorylated histone 3, a cell proliferation marker in the developing jaw.
      Taken together, our data suggest that Ahr2-mediated downregulation of Hh
      signaling, leading to a failure of cell proliferation, contributes to TCDD
      induced inhibition of lower jaw growth. TCDD may impair jaw growth through other
      pathway(s) in addition to Hh signaling.

PMID- 16580746
TI  - Effects of seawater pollutants on protein tyrosine phosphorylation in mussel
      tissues.
AB  - Different exogenous compounds are known to stimulate tyrosine kinase signaling,
      and this could explain a wide spectrum of pollutant effects on different
      organisms. We studied the effects of various seawater contaminants on tyrosine
      phosphorylation levels in different tissues of the mussel (Mytilus edulis), by
      using Western immunoblotting. Mussels were exposed in aquarium for 3 weeks to
      North Sea oil alone or to a mixture of North Sea oil, alkyl phenols, and
      polycyclic aromatic hydrocarbons (PAH). In another experiment, mussels were
      exposed for 3 weeks to each of the following potential endocrine disruptors:
      bisphenol A, diallyl phthalate, or tetrabromodiphenylether-47. In a third
      experiment, mussels were caged at four sites along a copper field gradient. Use
      of antiphosphotyrosine antibody showed that treatments with oil alone, or with
      oil, alkyl phenols and PAH induced phosphorylation increases in the digestive
      gland, gills and mantle. Bisphenol A produced significant effects in the gills
      and mantle, while diallyl phthalate and tetrabromodiphenylether-47 had a slight
      effect only on the gill tissue. Mussels exposed to the copper field gradient
      showed phosphotyrosine increases in the gills and mantle at intermediate levels
      of contamination. This latter result was also confirmed by using phosphospecific
      p38 antibody. In summary, the strength of induction was: oil
      mixture>oil>bisphenol A> or =copper; while the degree of tissue responsiveness
      was: mantle>gill>digestive gland. Based on these data, the use of tyrosine
      phosphorylation levels as a biomarker of seawater pollution is proposed.

PMID- 16580745
TI  - Toxin release in response to oxidative stress and programmed cell death in the
      cyanobacterium Microcystis aeruginosa.
AB  - An unprecedented bloom of the cyanobacterium Microcystis aeruginosa Kutz.
      occurred in the St. Lucie Estuary, FL in the summer of 2005. Samples were
      analyzed for toxicity by ELISA and by use of the polymerase chain reaction (PCR)
      with specific oligonucleotide primers for the mcyB gene that has previously been
      correlated with the biosynthesis of toxic microcystins. Despite the fact that
      secreted toxin levels were relatively low in dense natural assemblages (3.5
      microg l(-1)), detectable toxin levels increased by 90% when M. aeruginosa was
      stressed by an increase in salinity, physical injury, application of the chemical
      herbicide paraquat, or UV irradiation. The application of the same stressors
      caused a three-fold increase in the production of H(2)O(2) when compared to non
      stressed cells. The application of micromolar concentrations of H(2)O(2) induced
      programmed cell death (PCD) as measured by a caspase protease assay. Catalase was
      capable of inhibiting PCD, implicating H(2)O(2) as the inducing oxidative
      species. Our results indicate that physical stressors induce oxidative stress,
      which results in PCD and a concomitant release of toxin into the surrounding
      media. Remediation strategies that induce cellular stress should be approached
      with caution since these protocols are capable of releasing elevated levels of
      microcystins into the environment.

PMID- 16580750
TI  - Apoptosis in chronic heart failure.

PMID- 16580749
TI  - JPO1/CDCA7, a novel transcription factor E2F1-induced protein, possesses
      intrinsic transcriptional regulator activity.
AB  - JPO1/CDCA7 was originally identified as a c-Myc-responsive gene that participates
      in neoplastic transformation. Here, we report the identification of JPO1/CDCA7 as
      a direct transcriptional target of transcription factor E2F1. We demonstrated
      that overexpression of E2F1 by adenoviral-mediated gene transfer upregulated
      JPO1/CDCA7 mRNA expression in human cells. Analysis of human and mouse JPO1/CDCA7
      promoter constructs showed that an E2F-responsive sequence was necessary for E2F1
      induced activation of the JPO1/CDCA7 gene transcription. Among the members of the
      E2F family, E2F1 to E2F4, but not E2F5 or E2F6, activated the JPO1/CDCA7 reporter
      construct. Chromatin immunoprecipitation analysis demonstrated that E2F1, E2F2,
      and E2F4 specifically bound to an E2F-responsive sequence of the human JPO1/CDCA7
      gene. Like JPO2/R1, which has a homologous transcriptional regulator domain, the
      C-terminal cysteine-rich region of JPO1/CDCA7 protein induced transcriptional
      activity in a mammalian one-hybrid assay. Taken together, our results suggest
      that JPO1/CDCA7 is a unique transcription regulator whose expression is activated
      by E2F1 as well as c-Myc.

PMID- 16580751
TI  - Creation of standardized tools for therapeutic education specifically dedicated
      to chronic heart failure patients: the French I-CARE project.
AB  - AIM: To develop educational programs in chronic heart failure (CHF), creation of
      standardized tools for therapeutic education specifically dedicated to CHF
      patients was performed as a part of the French I-CARE project. METHODS AND
      RESULTS: A working group was constituted of cardiologists, nurses and dieticians,
      specialized in both therapeutic education and CHF. The personal patient's
      document consisted of a ring binder with dividers containing index cards for 5
      units. The unit "Educational diagnosis" comprised a guide for the user and an
      auto-questionnaire for the patient. The unit "Knowledge of the disease" comprised
      a whiteboard for explaining cardiovascular physiology, a 3D-model of heart, and a
      glossary. The unit "Diet control" was composed of posters, a food-card game with
      a game mat figuring the different meals of a day, a low-salt recipe book, and 1-g
      salt spoons. The unit "Physical activity and daily life" comprised
      recommendations for physical activity and questionable real-life situations, and
      a card game for evaluation. The unit "Medical treatment" consisted of index cards
      for different cardiovascular drugs. CONCLUSION: These educational tools should
      help multidisciplinary teams to develop therapeutic education dedicated to CHF in
      order to improve self-management, morbidity and quality of life in CHF patients.

PMID- 16580752
TI  - Case report: recurrent heart failure with preserved ejection fraction but
      markedly elevated BNP in a 51-year-old female on hemodialysis with oversized AV
      fistula.
AB  - We hereby report a case that appeared to have had recurrent clinical heart
      failure secondary to high-output state due to oversized arteriovenous fistula.
      Patient started to have dyspnea on exertion approximately 4 months after the
      creation of the fistula, and subsequently had two episodes of heart failure
      exacerbation. On both occasions, she had normal left ventricular systolic
      function as demonstrated by echocardiogram. The shunt was estimated to be as
      large as 1.9 L/min. B-type natriuretic peptide (BNP) levels were markedly
      elevated. To our knowledge, this is the first case in which BNP level was
      reported and used in the diagnosis of high-output heart failure.

PMID- 16580753
TI  - Working hours and ill-health--a more serious relationship than it appears?

PMID- 16580754
TI  - One of the most frequent vascular diseases in northeastern of Turkey:
      Thromboangiitis obliterans or Buerger's disease (experience with 344 cases).
AB  - PURPOSE: This is a retrospective clinical study on adult patients treated
      surgically for Buerger's disease in our region. METHODS: In our clinic, 344
      patients with Buerger's disease were surgically treated between 1980 and 2004.
      The major complaints included foot coldness in 312 (90.6%) patients, color
      changes in 290 (84.3%), rest pain in 160 (46.5%), claudication in 166 (48.2%) and
      necrotic ulcers in 185 (53.1%). Lumbar sympathectomy was made in 278 (80.2%)
      patients, thoracic sympathectomy in 7 (2.2%), thoracic and lumbar sympathectomy
      in 12 (3.6%), lumbar sympathectomy and femoropopliteal or femorotibial bypass in
      30 (9%), and femoropopliteal or femorotibial bypass in 17 (5%). RESULTS: Color
      changes were improved in 230 (79.3%) patients, food coldness were decreased in
      288 (92.3%) and rest pains were improved in 43 (26.8%). Intermittent
      claudications decreased in 132 of 166 patients. Necrotic ulcers healed in 30 of
      185 patients. Amputation was made totally in 155 (53%) patients in 10 years.
      CONCLUSIONS: As a nonatherosclerotic, segmental, inflammatory disease, Buerger's
      disease is casually related to tobacco use. The main goal is to discontinue the
      use of tobacco. Sympathectomy may be helpful in healing the ulcers and decreasing
      the symptoms. Vascular reconstruction is rarely possible for patients with
      Buerger's disease due to segmental involvement and distal nature of the disease.

PMID- 16580755
TI  - Unilateral pulmonary oedema due to lung re-expansion following pleurocentesis for
      spontaneous pneumothorax. The role of non-invasive continuous positive airway
      pressure ventilation.
AB  - Re-expansion pulmonary oedema represents a rare complication of treatment of
      spontaneous pneumothorax with only a few cases documented in the current
      literature. We present the case of a 47-year-old male who presented a right-sided
      spontaneous pneumothorax and developed respiratory failure after chest tube
      drainage. The diagnosis of re-expansion pulmonary oedema was made and he was
      successfully treated with non-invasive continuous positive airway pressure
      ventilation. Since pathogenesis of re-expansion unilateral pulmonary oedema
      differs significantly from that of cardiogenic pulmonary oedema, the role of non
      invasive continuous positive airway pressure ventilation is discussed as an
      additional therapeutic option.

PMID- 16580756
TI  - Usage of veterinary therapeutic antimicrobials in Denmark, Norway and Sweden
      following termination of antimicrobial growth promoter use.
AB  - Antimicrobial growth promoters (AGPs) were phased out in Denmark, Norway and
      Sweden in 1998-1999, 1995 and 1986, respectively. The annual usage of therapeutic
      antimicrobials in animals in Denmark almost doubled during the period when AGPs
      were phased out (1988-1999) and in the subsequent 2 years. The increase was
      mainly due to an increased consumption of therapeutic antimicrobials in weaning
      pigs. The annual increase in usage of therapeutic antimicrobials and the annual
      increase in numbers of slaughter-swine produced in Denmark correlates well,
      except for 1999 when AGP use was discontinued in weaning pigs, and the following
      year. In Norway, the usage of therapeutic antimicrobials in animals decreased by
      39% from 1995 to 2000. During 2001-2003 the annual usage remained at the 2000
      level. The annual numbers of slaughter-swine produced in Norway increased
      gradually by 10% after the AGP discontinuation (from 1995 to 2003). In Sweden,
      the usage of therapeutic antimicrobials in animals increased by 21% the first 2
      years subsequent to the AGP ban (1986-1988), remained then constant until 1994;
      from 1994 to 2003 this usage declined by 47%. The initial increase was caused by
      increased use in broilers and in weaning piglets. The amounts used in animals in
      Sweden in 2003 were half of the amounts used in 1994. The annual numbers of
      slaughter-swine produced in Sweden declined gradually by 16% in the study period,
      although fluctuating. In Denmark, Norway and Sweden the number of dairy cattle
      and beef cattle declined only slightly in the various study periods while numbers
      of broilers produced increased notably, especially in Norway and Sweden.
      Following the termination of AGPs the total usage of antimicrobials (AGPs and
      therapeutic antimicrobials) in animals in Denmark declined 36% (from 1996 to
      2003): in Norway this figure was 45% (from 1995 to 2003). In Sweden, the total
      usage of antimicrobials in animals in 2003 amounted to only one third of the
      amounts used in 1984 (decreased from 51 to 16 tonnes). Termination of AGPs was
      only a temporary risk factor for increased usage of therapeutic antimicrobials in
      food-animals in Sweden and Denmark; however, an exception might be usage in
      weaning piglets in Denmark. Furthermore, the discontinuation of AGP use has
      decreased the overall annual usage of antimicrobials in animals in Denmark,
      Norway and Sweden considerably.

PMID- 16580758
TI  - Magnitude of dyslipedemia and its association with micro and macro vascular
      complications in type 2 diabetes: a hospital based study from Bikaner (Northwest
      India).
AB  - AIM: Type 2 diabetes is not only associated with hyperglycemia but also with
      disorders of lipid metabolism. The aim of this study was to investigate the
      association of dyslipedemia with micro and macro vascular complications of
      diabetes. METHODS: Population based cross sectional study included 4067 diabetic
      patients who visited hospital during January 2000 to December 2002. Lipid profile
      was estimated by semi autoanalyser, Retinopathy was assessed by fundoscopy,
      Nephropathy by microalbuminurea, coronary artery disease (CAD) by electro
      cardiogram (ECG) changes, peripheral vascular disease (PVD) by doppler study and
      neuropathy by clinical examinations. The association of dyslipedemia with micro
      and macro vascular complications was assessed by regression analysis. RESULTS:
      The prevalence of dyslipedemia is high in diabetic population with high serum
      cholesterol >240mg/dl was seen in 15%, serum triglycerides >160mg/dl was seen in
      42.41%, raised LDL >130mg/dl in 45.26%, VLDL >40mg/dl in 24.09% and low levels of
      HDL-C <40mg/dl were seen in 52.27%. On regression analysis, CAD had strong
      correlation with high levels of VLDL (0.76), triglycerides (0.82), LDL (0.23) and
      low HDL (-0.81). Similar association was seen with PVD. Diabetic retinopathy and
      nephropathy were found to have significant correlation with low HDL (-0.43) and
      raised LDL (0.37), respectively. Neuropathy was not found to have any significant
      correlation with lipid profile abnormalities. CONCLUSION: Lipid profile
      abnormalities are very common in type 2 diabetes and it has great influence on
      CAD and PVD. Hence, appropriate preventive and treatment strategies should be
      considered timely.

PMID- 16580760
TI  - Long-term effectiveness against cholera of oral killed whole-cell vaccine
      produced in Vietnam.
AB  - We assessed the long-term protection afforded by a killed whole-cell oral cholera
      vaccine produced in Vietnam. A mass immunization of children and adults with the
      killed whole-cell oral cholera vaccine was undertaken in half of the communes of
      Hue, Vietnam, in 1998; the remaining communes were immunized in 2000. No cholera
      was observed in Hue until 2003, when an outbreak of El Tor cholera made it
      possible to conduct a case-control study. The overall vaccine effectiveness 3-5
      years after vaccination was 50% (9-63%). This low-cost, easily administered
      vaccine should be considered as a tool for the control of cholera.

PMID- 16580759
TI  - Self-prediction of hedonic trajectories for repeated use of body products and
      foods: poor performance, not improved by a full generation of experience.
AB  - This study extends earlier work by [Kahneman, D., and Snell, J. (1992).
      Predicting a changing taste: Do people know what they will like? Journal of
      Behavioral Decision Making, 5, 187-200.]. suggesting that people are poor at
      predicting changes in liking. This is an important issue because an absence of
      this ability would make it difficult for people to optimize their own choices.
      Twenty undergraduates and 20 of their parents sampled four relatively unfamiliar
      consumer products, two foods and two body products, for 8 days. On Day 1,
      participants rated their initial liking and predicted their liking after seven
      daily uses of the products. Predictions were compared to actual liking on Day 8.
      Consistent with prior work, participants were poor at predicting their actual
      hedonic trajectories because they underestimated the degree to which their
      preferences would change. Contrary to predictions, parents were no better than
      students at this task, even though they had some 20-39 years more experience in
      observing their own hedonic trajectories. There is no evidence for any parent
      child resemblance in either liking for the products or ability to accurately
      predict hedonic trajectory, and no evidence for consistency in ability to predict
      trajectories across the four different products. In general, participants
      underestimate the degree to which their preferences will change.

PMID- 16580757
TI  - 5-HT(2C) receptor RNA editing in the amygdala of C57BL/6J, DBA/2J, and BALB/cJ
      mice.
AB  - Post-transcriptional RNA editing of the G-protein coupled 5-hydroxytryptamine-2C
      (5-HT(2C)) receptor predicts an array of 24 receptor isoforms, some of which are
      characterized by reduced constitutive activity and potency to initiate
      intracellular signaling. The amygdala is integral to anxiety, fear, and related
      psychiatric diseases. Activation of 5-HT(2C) receptors within the amygdala is
      anxiogenic. Here, we describe the RNA editing profiles from amygdala of two
      inbred mouse strains (BALB/cJ and DBA/2J) known to be more anxious than a third
      (C57BL/6J). We confirmed the strain anxiety differences using light<-->dark
      exploration, and we discovered that BALB/cJ and DBA/2J are each characterized by
      a higher functioning RNA editing profile than C57BL/6J. BALB/cJ and DBA/2J
      exhibit a roughly two-fold reduction in C site editing, and a corresponding two
      fold reduction in the edited isoform VSV. C57BL/6J is characterized by a relative
      decrease in the unedited highly functional isoform INI. We estimated the
      heritability of editing at the C site to be approximately 40%. By sequencing
      genomic DNA, we found complete conservation between C57BL/6J, BALB/cJ, DBA/2J and
      37 other inbred strains for the RNA edited region of Htr2c, suggesting Htr2c DNA
      sequence does not influence variation in Htr2c RNA editing between inbred strains
      of mice. We did, however, discover that serotonin turnover is reduced in BALB/cJ
      and DBA/2J, consistent with emerging evidence that synaptic serotonin levels
      regulate RNA editing. These results encourage further study of the causes and
      consequences of 5-HT(2C) receptor RNA editing in the amygdala of mice.

PMID- 16580763
TI  - Heavy metals contents in agricultural topsoils in the Ebro basin (Spain).
      Application of the multivariate geoestatistical methods to study spatial
      variations.
AB  - In this work the content of seven heavy metals (Cd, Cr, Cu, Hg, Ni, Pb and Zn)
      and other parameters (the pH, organic matter, carbonates and granulometric
      fraction) in agricultural topsoil in the Ebro basin are quantified, based on 624
      samples collected according to an 8 by 8 km square mesh. The average
      concentrations (mg/kg) obtained were: Cd 0.415+/-0.163, Cr 20.27+/-13.21, Cu
      17.33+/-14.97, Ni 20.50+/-22.71, Pb 17.54+/-10.41, Zn 17.53+/-24.19 and Hg 35.6+/
      42.05 microg/kg. The concentration levels are relatively low in areas of high pH
      and low organic matter content concentration. The results of factor analysis
      group Cd, Cu, Hg, Pb and Zn in F1 and Cr y Ni in F2. The spatial heavy metals
      component maps based on geostatistical analysis, show definite association of
      these factors with the soil parent material. The local anomalies (found in Cu, Zn
      and Pb) are attributed to anthropogenic influence.

PMID- 16580761
TI  - Re: Kissun D, Shaw R J, Vaughan E D. Survival of a free flap after arterial
      disconnection at six days. Br J Oral Maxillofac Surg 2004;42:163-5.

PMID- 16580765
TI  - Are cholinergic enhancers beneficial for memory in schizophrenia? An event
      related potentials (ERPs) study of rivastigmine add-on therapy in a crossover
      trial.
AB  - Studies have reported beneficial effects of cholinergic enhancers, e.g.,
      rivastigmine, on memory in schizophrenia but others have not. Possibly, these
      discrepancies are related to the lack of specificity of the tests used. This
      study investigated the effect of rivastigmine on memory in schizophrenia using
      event-related potentials (ERPs). Eighteen patients treated with atypical
      antipsychotic received rivastigmine adjuvant therapy in a randomized, crossover
      design. They were assessed at baseline (T1) and on two subsequent occasions (T2
      and T3), where one half of the subjects were taken rivastigmine and the other
      half not. ERPs were recorded during a recognition memory task on each session.
      Behavioral and ERP data were analyzed using mixed ANOVA models first at T1 to
      detect potential group differences and for the trial (T1-T2) to determine the
      influence of rivastigmine, i.e., sessionxgroup interactions. The results showed
      no group difference at T1 except a trend for one group to be less efficient than
      the other on RT measures. When controlling for this difference the results on the
      trial data showed a trend for a benefit of rivastigmine on the RT memory effect.
      ERP analysis revealed that rivastigmine affects the amplitudes of two components
      elicited within 150-300 ms over posterior (reduced N2b) and frontal sites
      (enhanced P2a). It also enhances the magnitude of the memory (old/new) effect on
      two later components over posterior (N400) and frontal sites (F-N400). These
      results suggest that rivastigmine improves selective attention by enhancing
      interference inhibition processes (P2a) and lowering the reactivity to incoming
      stimulus (N2b). It also improves the integration of information with knowledge
      (N400) and with its context (F-N400). Generally, this study showed that the
      beneficial effect of rivastigmine on memory is not unitary but rather comes from
      its action at different time points within information processing cascade.

PMID- 16580766
TI  - Acute dystonia after initial doses of ziprasidone: a case report.
AB  - We present the case of an 18-year-old man, who was admitted with an obsessive
      compulsive disorder (OCD) since 17 years old. He had symmetry and contamination
      obsessions and cleaning compulsions, and had been treated with fluoxetine 40
      mg/day for 2 months. The patient was not taking additional psychotropic
      medication. We made ziprasidone augmentation to the treatment. First day,
      ziprasidone 40 mg bid was applied. Four hours after the evening dose, the patient
      complained about distress. He demonstrated a notable torticollis and dystonic
      posture to his left side. Intramuscular biperiden lactate (5 mg) was given, and
      dystonic symptoms resolved within 30 min. Ziprasidone is a new atypical
      antipsychotic with reported low potential for extrapyramidal side effects. To our
      knowledge, acute dystonic reaction with initial doses of ziprasidone in adult has
      not been reported yet. This case report describes a male patient with OCD
      developed acute dystonia shortly after initial doses (80 mg/day) of ziprasidone
      and discusses precautions in antipsychotic use.

PMID- 16580764
TI  - Symptoms, attitudes and treatment choices surrounding menopause among the Q'eqchi
      Maya of Livingston, Guatemala.
AB  - The present study explored symptoms, attitudes and treatments surrounding women's
      health and menopause among the Q'eqchi Maya of the eastern tropical lowlands of
      Guatemala. Data were obtained through participant observation, semi-structured
      interviews, focus groups and plant walks with 50 Q'eqchi community members from
      the state of Izabal, Municipality of Livingston, including five midwives, five
      traditional male healers and eight postmenopausal women. Results indicate that
      the Q'eqchi Maya of Livingston possess their own cultural perceptions of women's
      health which affect attitudes, symptoms and treatment choices during the
      menopausal transition. Since discussions of menstruation and menopause are
      considered cultural taboos among the Q'eqchi, many women mentioned experiencing
      excessive preoccupation when unanticipated and unfamiliar symptoms occurred.
      Furthermore, many women suffered from additional hardship when their spouse
      misinterpreted menopausal symptoms (vaginal dryness, sexual disinterest) as
      infidelity. Seven of the eight postmenopausal women interviewed indicated
      experiencing one or more symptoms during the menopausal transition, including
      headaches, anxiety, muscular pain, depression, and hot flashes. These results
      differ from the lack of symptomatology reported in previous studies in Mexico,
      but are in line with the result of menopausal research conducted among other Maya
      groups from the highlands of Guatemala. Although the Q'eqchi did not use a
      specific term for "hot flash", three Q'eqchi women used the expression "baja
      presion" or a "lowering of blood pressure" to explain symptoms of profuse
      sweating followed by chills, heart palpitations, and emotional instability. The
      Q'eqchi Maya mentioned a number of herbal remedies to treat menopausal symptoms.
      Further research on these botanical treatments is needed in order to ascertain
      their safety and efficacy for continued use.

PMID- 16580767
TI  - Involvement of adenosine in the neurobiology of schizophrenia and its therapeutic
      implications.
AB  - Based on the neuromodulatory and homeostatic actions of adenosine, adenosine
      dysfunction may contribute to the neurobiological and clinical features of
      schizophrenia. The present model of adenosine dysfunction in schizophrenia takes
      into consideration the dopamine and glutamate hypotheses, since adenosine exerts
      neuromodulatory roles on these systems, and proposes that adenosine plays a role
      in the inhibitory deficit found in schizophrenia. Given the role of adenosine
      activation of adenosine A1 receptor (A1R) in mediating neurotoxicity in early
      stages of brain development, pre- and peri-natal complications leading to
      excessive adenosine release could induce primary brain changes (i.e., first hit).
      These events would lead to an adenosine inhibitory deficit through a partial loss
      of A1R that may emerge as reduced control of dopamine activity and increased
      vulnerability to excitotoxic glutamate action in the mature brain (i.e., second
      hit). Adenosine dysfunction is reasonably compatible with symptoms, gray and
      white matter abnormalities, progressive brain loss, pre- and peri-natal risk
      factors, age of onset, response to current treatments, impaired sensory gating
      and increased smoking in schizophrenia. Pharmacological treatments enhancing
      adenosine activity could be effective for symptom control and for alleviating
      deterioration in the course of the illness. Accordingly, allopurinol, which may
      indirectly increase adenosine, has been effective and well tolerated in the
      treatment of schizophrenia. Since much of the evidence for the adenosine
      hypothesis is preliminary and theoretical, further investigation in the field is
      warranted.

PMID- 16580768
TI  - Serotonin transporter polymorphisms and clinical response to sertraline across
      ethnicities.
AB  - The aim of this pilot study was to examine the relationship between clinical
      response, adverse effects, sertraline (SERT) plasma concentrations and the
      genetic polymorphism of the serotonin transporter gene-linked polymorphic region
      (5HTTLPR) in 2 ethnic patient groups. The study involved 45 patients in a
      clinical trial who received a fixed dose regimen of 50 mg SERT for one week, then
      a variable-dose regimen for a further 6 weeks for major depressive disorder. At
      weeks 1 and 6, the following assessments were completed: Hamilton Depression
      Rating Scale (HDRS), Clinical Global Impression (CGI), drug adverse reaction
      scale and measurement of plasma SERT levels. Genomic analysis for the long and
      short allele variants of the 5HTTLPR polymorphism was also carried out. Caucasian
      subjects had a higher rate of l/l genotype while Chinese subjects had higher
      frequencies of l/s and s/s genotypes. Comparison of the subjects with the 5HTTLPR
      s/s genotype and those with the l/l and l/s genotypes found no significant
      differences in the HDRS scores, CGI scores, response rates, adverse effects and
      SERT plasma concentrations at week 6.

PMID- 16580771
TI  - Detergent solubilization of bovine erythrocytes. Comparison between the insoluble
      material and the intact membrane.
AB  - Early works have shown that when biomembranes are extracted with the non-ionic
      detergent Triton X-100 at 4 degrees C, only a subset of the components is
      solubilized. The aim of this paper was to investigate the solubilization of a
      cell membrane at different Triton concentrations, and to compare the lipid
      composition and acyl chain order/mobility of the insoluble material with those of
      the original membrane. We choose bovine erythrocytes, because they have an
      uncommon composition, as they have a huge amount of sphingomyelin and
      phosphatidylcholine is almost absent. We determined the degree of order/mobility
      of the lipid acyl chains by EPR spectroscopy, using liposoluble spin labels.
      Incubation of bovine erythrocytes with increasing Triton X-100 concentrations
      yields decreasing amounts of insoluble material which is enriched in
      sphingomyelin and depleted in cholesterol. Complete lipid solubilization is
      achieved at a detergent/lipid ratio of about 60, which is much higher than the
      values reported for human erythrocytes, but is in line with results obtained in
      model systems. An insoluble pellet is still obtained at higher Triton
      concentrations, which seems to consist mainly of protein. A very high correlation
      is found between lipid chain mobility restrictions and sphingomyelin content in
      the lipid structures. The human erythrocyte membrane also fits well in this
      correlation, suggesting a significant role of sphingomyelin in determining acyl
      chain organization. The analogies and differences between our insoluble material
      and the detergent-resistant membranes (DRM) are discussed.

PMID- 16580770
TI  - Salubrious effects of lipoic acid against adriamycin-induced clastogenesis and
      apoptosis in Wistar rat bone marrow cells.
AB  - Adriamycin (ADR), an anthracycline antibiotic, which is widely used as an
      antineoplastic drug in the treatment of various solid tumors, has been shown to
      induce genotoxicity in erythropoietic system. The aim of the present study was to
      investigate the protective efficacy of DL-alpha-lipoic acid (LA) on ADR-induced
      clastogenicity and apoptosis in the bone marrow of rats. The animals were
      randomly divided into eight groups consisting of six rats each. Five groups were
      administered ADR (20 mg/kg body weight, i.v.) to induce genotoxicity; four of
      these groups received a single intraperitoneal injection of LA at a dose of
      either 100 or 200 mg/kg body weight, and either 30 or 60 min prior to ADR
      administration. A vehicle treated control group and LA control groups were also
      included. The beneficial effects of LA were monitored by DNA strand breaks,
      chromosomal aberrations, micronucleus assay and apoptotic studies in the bone
      marrow cells of rats after 24 h following single dose of ADR treatment. ADR
      treatment caused significant clastogenicity and apoptosis in rat bone marrow
      cells. The treatment with LA showed significant reduction in the frequency of
      chromosomal aberrations, DNA strand breaks and apoptosis in bone marrow cells as
      well as decreased the micronuclei formation in bone marrow and peripheral blood
      of rats treated with ADR. The protective effect of LA was found to be stronger at
      a dose of 200 mg/kg body weight than 100 mg/kg body weight dosage with respect to
      the above results, indicating the dose dependent effect of LA. However, the
      protection by LA was not dependent on the time intervals between LA and ADR
      administration. The results of this study illustrate the protective effect of LA
      on ADR-induced clastogenicity and apoptosis in the erythropoietic system of rats.

PMID- 16580769
TI  - Influence of diets with cereal grains contaminated by graded levels of two
      Fusarium toxins on selected enzymatic and histological parameters of liver in
      gilts.
AB  - Feeding experiments with diets containing Fusarium toxin-contaminated wheat were
      conducted to clarify the pathogenesis of enzymatic and histopathological effects
      of Fusarium toxins on porcine liver cells. A total of 36 prepuberal gilts were
      divided into four groups and fed diets with increasing proportions of Fusarium
      toxin-contaminated wheat at a total wheat proportion of 40% over a period of 35
      days. The concentrations of the indicator toxins deoxynivalenol (DON) and
      zearalenone (ZON) which were analyzed by HPLC methods were 210/4, 3070/88,
      6100/235, and 9570/358 microg/kg in the diets fed to groups I-IV, respectively.
      The feeding of mycotoxin-contaminated diets did not cause gross pathological
      findings in the livers of the animals. Liver tissues were subjected to enzymatic,
      histological, and ultrastructural examinations. The percentages of the stained
      areas in periodic acid-Schiff (PAS), Berlin-Blue, and Masson Goldner's trichrome
      stainings were calculated using the AnalySIS 3.4-system. Significant
      histopathological findings of alterations with varying degrees in glycogen
      reduction and increase of hemosiderin particles were found in the liver cells of
      groups II, III and IV. The thickness of interlobular connective tissue septum in
      liver cells was significantly increased in groups III and IV. Qualitative
      ultrastructural alterations were observed in hepatocytes of gilts in groups III
      and IV. Dependent upon the mycotoxin concentration in the diet, the hepatocytes
      developed a dose-dependent, extensive, smooth endoplasmic reticulum, exhibited
      loss of ribosomes, and acquired an increased number of fatty and autophagic
      vacuoles. However, liver damage as measured by prominent elevated transaminase
      activities in serum was not detected. Together, the histopathological results
      provide evidence of liver dysfunction in the absence of clinical signs,
      especially in pigs fed higher concentrations of Fusarium toxin-contaminated
      wheat.

PMID- 16580772
TI  - Hormonal approaches to male contraception: approaching reality.
AB  - The 'pre-testicular' suppression of gonadotrophins is the most likely approach
      for reversible therapeutic male fertility control to reach imminent clinical
      application. Maintenance of spermatogenesis depends on adequate gonadotrophin and
      intratesticular testosterone concentrations. Hormonal contraception for men
      interrupts this physiological axis by various means of gonadotrophin suppression;
      this interferes with spermatogonial differentiation and meiosis entry resulting
      in reversible azoospermia or severe oligozoospermia in virtually all men.
      Clinical trials have confirmed that high contraceptive efficacy, similar to
      female hormonal contraceptives, can be reliably attained with few side effects.
      However, the simultaneous suppression of Leydig cell steroidogenesis mandates the
      requirement for testosterone replacement in hormonal male contraception.
      Combination regimens of new synthetic progestins and androgens at various stages
      of development are being investigated with the lead products poised to go into
      phase III trials. Heterogeneity in response to spermatogenesis suppression has
      been observed within and between population; the mechanisms are unclear. This new
      method of reversible and effective contraception has registered high
      acceptability in surveys of both men and women. The recent entry of
      pharmaceutical companies into this area of research and development has
      considerably enhanced the prospects of translating years of academic efforts into
      new products which provide added family planning choice for many couples.

PMID- 16580776
TI  - Oxidative status of valinomycin-resistant normal, beta-thalassemia and sickle red
      blood cells.
AB  - Exposure of red blood cells (RBC) to the K+ -ionophore valinomycin (val), causes
      loss of KCl and water, resulting in cell dehydration, manifested by increased
      cell density. While almost all normal val-treated RBC dehydrate, in sickle cell
      anemia (SCA) a portion of the RBC fail to dehydrate and maintain a light density,
      indicating the existence of val-resistant (val-res) RBC. In thalassemia and
      sickle cell disease (SCD), although the primary lesion is in the globin genes,
      damage to the RBC is partly mediated by oxidative stress. We previously showed
      that such RBC are under oxidative stress, having more reactive oxygen species
      (ROS) and less reduced glutathione than normal RBC. We now report a relationship
      between the phenomenon of val-res and the RBC oxidative status: Treatment with
      oxidants that increase ROS, also increased the frequency of val-res cells. Val
      res cells had higher oxidative status than other RBC in the sample. Similar to
      SCA, thalassemic blood has more val-res cells than does normal blood. Val-res
      cells in thalassemic and sickle blood showed a higher oxidative status than
      normal val-res cells. Thus, oxidative stress might be involved in generation of
      val-res cells. Further studies are required to elucidate the origin and
      significance of these cells.

PMID- 16580775
TI  - Helminths of red foxes (Vulpes vulpes) in Denmark.
AB  - An epidemiological study of helminths in 1040 red foxes collected from various
      localities in Denmark during 1997-2002, revealed 21 helminth species at autopsy,
      including nine nematode species: Capillaria plica (prevalence 80.5%), Capillaria
      aerophila (74.1%), Crenosoma vulpis (17.4%), Angiostrongylus vasorum (48.6% from
      Northern Zealand (endemic area)), Toxocara canis (59.4%), Toxascaris leonina
      (0.6%), Uncinaria stenocephala (68.6%), Ancylostoma caninum (0.6%), and Trichuris
      vulpis (0.5%); seven cestodes: Mesocestoides sp. (35.6%), a number of Taeniid
      species (Taenia pisiformis, T. hydatigena, T. taeniaeformis, T. crassiceps, and
      unidentified Taenia spp.) (22.8%), and Echinococcus multilocularis (0.3%); four
      trematodes: Alaria alata (15.4%), Cryptocotyle lingua (23.8%), Pseudamphystomum
      truncatum (3.6% from Northern Zealand), and Echinochasmus perfoliatus (2.4% from
      Northern Zealand); one acanthocephalan: Polymorphus sp. (1.2%). Significant
      difference in prevalence was found for T. canis and A. vasorum according to host
      sex, and for T. canis, U. stenocephala, Mesocestoides sp., Taenia spp., A. alata,
      A. vasorum, and Capillaria spp. according to age groups (adult, young or cub).
      Prevalence and average worm intensity for each helminth species varied
      considerably according to geographical locality, season, and year. Aggregated
      distribution was found for several helminth species. The two species E.
      multilocularis and E. perfoliatus are first records for Denmark.

PMID- 16580778
TI  - Minor groove binding of Co(III)meso-tetrakis(N-methylpyridinium-4-yl)porphyrin to
      various duplex and triplex polynucleotides.
AB  - The binding site and the geometry of Co(III)meso-tetrakis(N-methylpyridinium-4
      yl)porphyrin (CoTMPyP) complexed with double helical poly(dA).poly(dT) and
      poly(dG).poly(dC), and with triple helical poly(dA).[poly(dT)](2) and
      poly(dC).poly(dG).poly(dC)(+) were investigated by circular and linear dichroism
      (CD and LD). The appearance of monomeric positive CD at a low [porphyrin]/[DNA]
      ratio and bisignate CD at a high ratio of the CoTMPyP-poly(dA).poly(dT) complex
      is almost identical with its triplex counterpart. Similarity in the CD spectra
      was also observed for the CoTMPyP-poly(dG).poly(dC) and 
      poly(dC).poly(dG).poly(dC)(+) complex. This observation indicates that both
      monomeric binding and stacking of CoTMPyP to these polynucleotides occur at the
      minor groove. However, different binding geometry of CoTMPyP, when bind to AT-
      and GC-rich polynucleotide, was observed by LD spectrum. The difference in the
      binding geometry may be attributed to the difference in the interaction between
      polynucleotides and CoTMPyP: in the GC polynucleotide case, amine group protrude
      into the minor groove while it is not present in the AT polynucleotide.

PMID- 16580777
TI  - Epitope mapping of the domains of human angiotensin converting enzyme.
AB  - Somatic angiotensin converting enzyme (sACE), contains in its single chain two
      homologous domains (called N- and C-domains), each bearing a functional zinc
      dependent active site. The present study aims to define the differences between
      two sACE domains and to localize experimentally revealed antigenic determinants
      (B-epitopes) in the recently determined three-dimensional structure of testicular
      tACE. The predicted linear antigenic determinants of human sACE were determined
      by peptide scanning ("PEPSCAN") approach. Essential difference was demonstrated
      between locations of the epitopes in the N- and C-domains. Comparison of
      arrangement of epitopes in the human domains with the corresponding sequences of
      some mammalian sACEs enabled to classify the revealed antigenic determinants as
      variable or conserved areas. The location of antigenic determinants with respect
      to various structural elements and to functionally important sites of the human
      sACE C-domain was estimated. The majority of antigenic sites of the C-domain were
      located at the irregular elements and at the boundaries of secondary structure
      elements. The data show structural differences between the sACE domains. The
      experimentally revealed antigenic determinants were in agreement with the
      recently determined crystal tACE structure. New potential applications are open
      to successfully produce mono-specific and group-specific antipeptide antibodies.

PMID- 16580780
TI  - The differential effects of volatile anesthetics on electrophysiological and
      biochemical changes during and recovery after hypoxia in rat hippocampal slice
      CA1 pyramidal cells.
AB  - Two volatile agents, isoflurane and sevoflurane have similar anesthetic
      properties but different potencies; this allows the discrimination between
      anesthetic potency and other properties on the protective mechanisms of volatile
      anesthesia. Two times the minimal alveolar concentration of an anesthetic is
      approximately the maximally used clinical concentration of that agent; this
      concentration is 2% for isoflurane and 4% for sevoflurane. We measured the
      effects of isoflurane and sevoflurane on cornus ammonis 1 (CA1) pyramidal cells
      in rat hippocampal slices subjected to 10 min of hypoxia (95% nitrogen 5% carbon
      dioxide) and 60 min of recovery. Anesthetic was delivered to the gas phase using
      a calibrated vaporizer for each agent. At equipotent anesthetic concentrations,
      sevoflurane (4%) but not isoflurane (2%), enhanced the initial hyperpolarization
      (6.7 vs. 3.4 mV), delayed the hypoxic rapid depolarization (521 vs. 294 s) and
      reduced peak hypoxic cytosolic calcium concentration (203 vs. 278 nM). While both
      agents reduced the final membrane potential at 10 min of hypoxia compared with
      controls, 4% sevoflurane had a significantly greater effect than 2% isoflurane (
      24.4 vs. -3.5 mV). The effect of these concentrations of isoflurane and
      sevoflurane was not different for sodium, potassium or ATP concentrations at 10
      min of hypoxia, the only difference at 5 min of hypoxia was that ATP was better
      maintained with 4% sevoflurane (2.2 vs. 1.3 nmol/mg). If the same absolute
      concentration (4%) of isoflurane and sevoflurane is compared then the cellular
      changes during hypoxia are similar for both agents and they both improve
      recovery. We conclude that an anesthetic's absolute concentration and not its
      anesthetic potency correlates with improved recovery of CA1 pyramidal neurons.
      The mechanisms of sevoflurane-induced protection include delaying and attenuating
      the depolarization and the increase of cytosolic calcium and delaying the fall in
      ATP during hypoxia.

PMID- 16580773
TI  - Connexin expression in mouse lung tumor.
AB  - Gap junction intercellular communication (GJIC) is considered to play roles in
      regulation of homeostasis, development and differentiation of many tissues. In
      the present study, using reverse transcription-polymerase chain reaction (RT-PCR)
      and in situ RT-PCR, we examined expression of Connexins (Cx26, 32, 37, 40, 43 and
      45) in the normal lung and lung tumors of mice to determine whether their
      expressions change during lung tumorigenesis. Cx26, 32 and 40 were expressed
      similarly in the normal lung tissue and tumors with smaller size (0.5-1.5mm)
      though expression of Cx32 and 40 decreased in tumors with larger size (>2.5mm).
      Cx26 was undetectable in larger size tumors. Cx37 and 45 were expressed in both
      normal lung and larger size tumors but no expression was seen in smaller size
      tumors. Cx43 was similarly detectable in normal lung, smaller size tumor and
      larger size tumor, but western blotting showed that Cx43 was phosphorylated
      during lung tumorigenesis. Thus, it is likely that alteration of expression of
      these Cx may be involved in expression of the neoplastic phenotype.

PMID- 16580784
TI  - The association of substance use disorders with trauma exposure and PTSD among
      African American drug users.
AB  - This study examines the association of traumatic exposure, PTSD and substance use
      among 1098 out-of-treatment African American drug users. Over 40% of the
      respondents experienced a DSM-III-R qualifying traumatic event with 44% of those
      developing PTSD. Early onsets of marijuana and heroin use, alcohol dependence and
      opiate dependence were each associated with exposure to a traumatic event for
      males and early onset alcohol use and alcohol dependence were associated with
      females' exposure to a traumatic event. Alcohol dependence and depression
      disorder were co morbid with PTSD in men, while the early onset of alcohol and
      alcohol dependence were associated with PTSD in women. In the 16% of the sample
      who reported trauma exposure and poly-substance use, the trauma occurred after
      the onset of all substance use, with the exception of crack cocaine use.
      Implications for multifaceted treatment which addresses multiple
      psychopathologies, PTSD, and risk for exposure are discussed.

PMID- 16580786
TI  - A paradigm for viewing biologic systems as scale-free networks based on energy
      efficiency: implications for present therapies and the future of evolution.
AB  - A network constitutes an abstract description of the relationships among
      entities, respectively termed links and nodes. If a power law describes the
      probability distribution of the number of links per node, the network is said to
      be scale-free. Scale-free networks feature link clustering around certain hubs
      based on preferential attachments that emerge due either to merit or legacy.
      Biologic systems ranging from sub-atomic to ecosystems represent scale-free
      networks in which energy efficiency forms the basis of preferential attachments.
      This paradigm engenders a novel scale-free network theory of evolution based on
      energy efficiency. As environmental flux induces fitness dislocations and compels
      a new meritocracy, new merit-based hubs emerge, previously merit-based hubs
      become legacy hubs, and network recalibration occurs to achieve system
      optimization. To date, Darwinian evolution, characterized by innovation sampling,
      variation, and selection through filtered termination, has enabled biologic
      progress through optimization of energy efficiency. However, as humans remodel
      their environment, increasing the level of unanticipated fitness dislocations and
      inducing evolutionary stress, the tendency of networks to exhibit inertia and
      retain legacy hubs engender maladaptations. Many modern diseases may
      fundamentally derive from these evolutionary displacements. Death itself may
      constitute a programmed adaptation, terminating individuals who represent legacy
      hubs and recalibrating the network. As memes replace genes as the basis of
      innovation, death itself has become a legacy hub. Post-Darwinian evolution may
      favor indefinite persistence to optimize energy efficiency. We describe
      strategies to reprogram or decommission legacy hubs that participate in human
      disease and death.

PMID- 16580790
TI  - Partial breast irradiation: a cautionary note.

PMID- 16580785
TI  - Potential usefulness of N1,N11-diethylnorspermine to prevent suicidal behaviour.

PMID- 16580787
TI  - Osteoarthritis: an example of phenoptosis through autonomic dysfunction?
AB  - Phenoptosis, the programmed death of organisms akin to cellular apoptosis,
      constitutes a type of Darwinian selection that enhances inclusive fitness. It
      provides a means by which senescent and pre-senescent members can self-terminate
      if they have incurred sufficient cumulative stress such that their continued
      survival detracts from inclusive fitness. Sepsis, vascular disease, menopause,
      cancer, and aging all represent examples of phenoptosis at work. We previously
      proposed that feed-forward autonomic dysfunction fundamentally drives phenoptosis
      in all its guises. Accordingly, we now postulate that osteoarthritis defines a
      type of biomechanical phenoptosis, mediated by feed-forward autonomic
      dysfunction, and manifested through joint destruction associated with fitness
      disadvantages. Biomechanical capability plays a significant role in evolutionary
      fitness, and sustained joint insults such as immobility or undue biomechanical
      stress may serve as proxies for inferior fitness. By both hindering an
      individual's ability to compete for energy and increasing that individual's
      vulnerability to predation, feed-forward joint destruction may facilitate
      adaptive phenoptosis among impaired or senile members. Empirical data suggests
      that contrary to common belief, heavy joint use does not necessarily cause
      osteoarthritis, whereas immobility and neuropathy can predispose to the
      condition. From a Darwinian perspective, another process mediated by sympathetic
      activity, the alarm cry of attacked prey, simultaneously promotes the escape of
      kin while attracting predators and scavengers. By effectively enabling the
      martyrdom of biomechanically-challenged individuals, osteoarthritis may serve to
      optimize system energy efficiency in a similar fashion. This framework may
      generalize to other situations where regenerative capacity dissipates in
      conjunction with maturation, typically leading to fibrosis. By allowing
      environmental pressure to sort the phenotypes, imperfect repair mechanisms may
      accelerate adaptation and optimize long-term inclusive fitness for all
      individuals. As the basis of competition shifts from biomechanical to cognitive
      skills, and as novel triggers for physical stress emerge, osteoarthritis may now
      represent a modern maladaptation.

PMID- 16580781
TI  - Altered expression of zinc transporters-4 and -6 in mild cognitive impairment,
      early and late Alzheimer's disease brain.
AB  - Accumulating evidence suggests that a disruption of zinc (Zn) homeostasis may
      play a role in the pathogenesis of Alzheimer's disease. Although several Zn
      transporter proteins responsible for the regulation of Zn balance are present in
      the brain, there has been little study of these proteins in Alzheimer's disease.
      To determine if alterations of Zn transporter proteins exist, levels of Zn
      transporter-4, which functions to remove Zn from the cytoplasm to
      endosomal/lysosomal compartments, and Zn transporter-6, which allocates
      cytoplasmic Zn to the trans-Golgi network, were measured in the
      hippocampus/parahippocampal gyrus, superior and middle temporal gyrus, and
      cerebellum of subjects with mild cognitive impairment, early Alzheimer's disease,
      late stage Alzheimer's disease, and age-matched controls using Western blot
      analysis and protein specific antibodies. Our results show that Zn transporter-4
      and Zn transporter-6 are significantly (P<0.05) increased in
      hippocampus/parahippocampal gyrus of early Alzheimer's disease and Alzheimer's
      disease subjects. Zn transporter-6 is also increased (P<0.1) in the superior and
      middle temporal gyrus of Alzheimer's disease brain.

PMID- 16580788
TI  - Protein ubiquitination, degradation and the proteasome in neuro-degenerative
      disorders: no clear evidence for a significant pathogenetic role of proteasome
      failure in Alzheimer disease and related disorders.
AB  - It has recently been proposed that Alzheimer disease (AD) might be initiated by a
      molecular 'hit' into a regulatory protein, e.g. a cell surface receptor [Schmitt
      HP. Neuro-modulation, aminergic neuro-disinhibition and neuro-degeneration: draft
      of a comprehensive theory for Alzheimer disease. Med Hypoth 2005;65:1106-19].
      However, other substrates, in particular intra-cellular protein complexes such as
      the ubiquitin/proteasome system (UPS) could as well serve as a targets for such a
      'hit' which might insert a mutation or induce conformational changes resulting in
      functional failure of protein degradation along the ubiquitin/proteasome
      proteolytic pathway. It has been claimed that impairment of the large multi
      catalytic protease complex, the 20S/26S proteasome, might represent a key factor
      in the early pathogenesis of neuro-degenerative disorders characterized by the
      formation of abnormal protein aggregates such as neuronal cytoplasmic or nuclear
      inclusion bodies and fibrillary deposits. This article aims to review critically
      whether current information really supports the idea that impairment of the UPS
      might play a significant role in the early pathogenesis of neuro-degenerative
      disorders, with special emphasis on AD. The data provided in favour of proteasome
      impairment were, as a rule, revealed in in vitro experiments which cannot be
      unequivocally transferred to the in vivo conditions in neuro-degeneration. The
      author concludes that there is yet no clear evidence of a pivotal role of
      proteasome failure in the early pathogenesis of AD.

PMID- 16580789
TI  - p53 protein or BID protein select the route to either apoptosis (programmed cell
      death) or to cell cycle arrest opposing carcinogenesis after DNA damage by ROS.
AB  - p53 is a tumour-suppressor protein of human cells that prevents their entry into
      the route to carcinogenesis. Furthermore, p53 protein acts at the p53-response
      loci in genomic DNA to facilitate the switch-on of genes that can be expressed by
      the biosynthesis of routing-proteins for apoptosis or stalling of cellular
      proliferation (via cell cycle progression checkpoint arrests). Moreover,
      oxidative stress by reactive oxygen species (ROS) such as the hydroxyl radical
      (*OH) produced by ionizing radiation (carcinogenic) triggers p53 activation in
      response to the damage of DNA (followed by initiation of DNA-repair mechanisms).
      Phosphorylation of the BID protein may lead to the recovery from DNA-damage by
      ROS.

PMID- 16580779
TI  - Lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate induction of
      migration and invasion of glioma cells in vitro and in vivo: Differential
      inhibitory effects of flavonoids.
AB  - In an earlier study, we reported that nitric oxide is involved in
      lipopolysaccharide plus 12-o-tetradecanoylphorbol 13-acetate-induced malignant
      transformation via increases in metalloproteinase 9 enzyme activity and inducible
      nitric oxide synthase gene expression in rat glioma C6 cells, however the
      mechanism has remained undefined. Lipopolysaccharide plus 12-o
      tetradecanoylphorbol 13-acetate, but not lipopolysaccharide or 12-o
      tetradecanoylphorbol 13-acetate alone, induced transformation in glioma C6 cells
      (but not in human glioblastoma cells GBM-8401 cells) without affecting their
      viability. An increase in inducible nitric oxide synthase protein expression,
      nitric oxide production, and metalloproteinase 9 enzyme activity is identified
      lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-treated C6 cells, however
      lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate and 12-o
      tetradecanoylphorbol 13-acetate (but not lipopolysaccharide) addition shows the
      similar inductive pattern on metalloproteinase 9 enzyme activity without
      affecting inducible nitric oxide synthase protein expression and nitric oxide
      production in GBM-8401 cells. Treatment of C6 cells with lipopolysaccharide/12-o
      tetradecanoylphorbol 13-acetate increases the expression of phosphorylated
      extracellular regulated protein kinases and Jun N-terminal kinases, but not p38,
      proteins, and an addition of the extracellular regulated protein kinases
      inhibitor PD98059 or Jun N-terminal kinases inhibitors SP600125, but not the p38
      inhibitor SB203580, significantly blocked lipopolysaccharide/12-o
      tetradecanoylphorbol 13-acetate-induced inducible nitric oxide synthase protein
      expression and metalloproteinase 9 enzyme activity accompanied by blocking
      morphological transformation in C6 cells. Among 19 structurally related
      flavonoids, kaempferol and wogonin exhibit significant inhibitory effects on
      lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate-induced morphological
      transformation and colony formation, and attenuation of inducible nitric oxide
      synthase, phosphorylated extracellular regulated protein kinases protein
      expression, and metalloproteinase 9 enzyme activity was observed. 2'-OH flavone
      at a dose of 100 microM inhibition of lipopolysaccharide/12-o
      tetradecanoylphorbol 13-acetate-induced events via apoptosis induction is
      identified. Furthermore, lipopolysaccharide/12-o-tetradecanoylphorbol 13-acetate,
      but not lipopolysaccharide or 12-o-tetradecanoylphorbol 13-acetate, induces
      tumoral invasion and migration in vitro and in vivo, and those are blocked by
      kaempferol and wogonin addition. These data suggest that combination of
      lipopolysaccharide and 12-o-tetradecanoylphorbol 13-acetate promotes tumoral
      progression via activating metalloproteinase 9 enzyme activity and inducible
      nitric oxide synthase gene expression, which is located downstream of mitogen
      activated protein kinases activation, in rat glioma cells C6. Kaempferol and
      wogonin exhibit effective inhibitory effects on lipopolysaccharide/12-o
      tetradecanoylphorbol 13-acetate-induced events, and thus possess the potential
      for further development.

PMID- 16580783
TI  - Single opioid administration modifies gonadal steroids in both the CNS and plasma
      of male rats.
AB  - While morphine remains one of the most widely used opioids for the treatment of
      painful conditions, other opioids are also commonly employed. Because of the
      interactions between opioids and gonadal hormones, in particular opioid-induced
      hypogonadism, this study investigated the effects of widely used opioids on
      plasma testosterone and estradiol levels and brain testosterone levels in male
      rats. Animals were s.c. injected with two concentrations of morphine (5 or 10
      mg/kg), fentanyl (0.05 or 0.1 mg/kg), tramadol (10 or 40 mg/kg), buprenorphine
      (0.05 or 0.1 mg/kg) or saline (0.7 ml/kg). Four or 24 h after treatment, the rats
      were deeply anesthetized to collect blood samples from the abdominal aorta and to
      perfuse the brains with saline. Plasma and brain hormone levels were measured by
      radioimmunoassay. In rats studied 4 h after treatment, all the opioids except
      tramadol 10 mg/kg decreased plasma testosterone in comparison with saline
      administration. At the same time, plasma estradiol levels were lower than control
      in the groups treated with the low doses of morphine, tramadol and buprenorphine,
      while estradiol remained at control levels in the other groups. Twenty-four hours
      after treatment, plasma testosterone levels were different (higher) than control
      in the animals treated with the low doses of morphine, fentanyl and
      buprenorphine. Estradiol was lower than control in the low dose groups, while the
      high doses did not produce any changes with respect to control. Four hours after
      treatment, brain testosterone was drastically decreased in all groups except
      buprenorphine, in which it remained at control levels. All groups returned to
      control levels at 24 h after treatment. In conclusion, opioids exert important
      effects on plasma and CNS sex hormone levels. The different magnitude and time
      course of the effects of the different opiates on testosterone and estradiol
      levels are likely due to their different mechanism of action.

PMID- 16580791
TI  - Phase I study of intraoperative radiotherapy with photon radiosurgery system in
      children with recurrent brain tumors: preliminary report of first dose level (10
      Gy).
AB  - PURPOSE: To describe the preliminary results after intraoperative radiotherapy
      (IORT) with the photon radiosurgery system in children with recurrent brain
      tumors treated at the first dose level (10 Gy) of a Phase I protocol. METHODS AND
      MATERIALS: A Phase I IORT dose escalation protocol was initiated at Children's
      Memorial Hospital to determine the maximal tolerated IORT dose in children with
      recurrent brain tumors. RESULTS: Fourteen children have received IORT thus far.
      Eight had been previously irradiated. Thirteen children had ependymoma. The
      median follow-up was 16 months. Three patients (21%) developed radiation necrosis
      on follow-up MRI scans 6 to 12 months after IORT. They had not been previously
      irradiated and had received 10 Gy to a depth of 5 mm. One required surgery and
      the other two had resolution of their lesions without treatment. All 3 patients
      were asymptomatic at the last follow-up. No other late toxicity was observed at
      the last follow-up visit. Eight patients (57%) had tumor control within the
      surgical bed after IORT. CONCLUSION: Our findings have demonstrated the safety
      and feasibility of IORT to a dose of 10 Gy to 2 mm in children with previously
      irradiated brain tumors. IORT to a dose of 10 Gy at 5 mm was associated with a
      greater complication rate.

PMID- 16580793
TI  - Two hexamerin genes from the termite Reticulitermes flavipes: Sequence,
      expression, and proposed functions in caste regulation.
AB  - Previous molecular studies on the termite Reticulitermes flavipes have revealed
      that two hexamerin proteins serve an important status quo role in the regulation
      of juvenile hormone (JH)-dependent caste differentiation. Here, we report
      sequence data and other experimental evidence suggesting how these two hexamerins
      function in achieving caste regulation. The two hexamerin genes, named Hex-1 and
      Hex-2, encode highly unique sequence features relative to the 100+ other known
      insect hexamerins. These features include a long hydrophobic tail and prenylation
      motif in Hex-1, and a long hydrophilic insertion plus several putative protease
      cleavage sites in Hex-2. Both hexamerin genes are primarily expressed in fat body
      tissue, but only Hex-2 expression is substantially induced by JH. SDS-PAGE showed
      that the hexamerin proteins constitute a major proportion of total soluble
      termite protein. Also, although each protein occurs in both the membrane and
      soluble protein fractions, Hex-2 has stronger membrane affinity. Anti-JH
      antiserum specifically recognizes hemolymph-soluble Hex-1 protein, supporting
      that the unique prenylation site in Hex-1 facilitates covalent JH binding to the
      primary amino acid chain. Finally, increased ratios of Hex-2 to Hex-1
      transcription occur in caste phenotypes and developmental stages that
      differentiate in response to rising JH titers. Two main conclusions can be taken
      from these studies. First, elevated ratios of Hex-2 to Hex-1 expression are
      associated with caste phenotypes that differentiate in response to rising JH
      titers (i.e., workers, presoldiers and soldiers). Second, due to their unique
      structural features and other observed characteristics, our findings support the
      hypothesis that the two hexamerins participate in the regulation of caste
      differentiation by modulating JH availability.

PMID- 16580792
TI  - Reductions in heroin use are not associated with increases in other drug use: 2
      year findings from the Australian Treatment Outcome Study.
AB  - AIMS: To determine whether reductions in frequency of heroin use were associated
      with reductions in the use of other drugs over a 24-month period. DESIGN:
      Longitudinal cohort, with follow-up at 3, 12 and 24 months. PARTICIPANTS: Six
      hundred and fifteen heroin users recruited for the Australian Treatment Outcome
      Study. SETTING: New South Wales, Australia. FINDINGS: The proportion reporting
      weekly heroin use declined significantly at 3, 12 and 24 months. Reductions in
      heroin use were associated with longer periods in both residential rehabilitation
      (RR) and maintenance treatment (MT). Less frequent use of other opioids, cocaine,
      amphetamine, cannabis and benzodiazepines were noted over follow-up, with alcohol
      use remaining stable. Across follow-up, lower frequency heroin use was associated
      with reduced likelihood of frequent use of other opioids, cocaine, amphetamine
      and benzodiazepines. Alcohol and cannabis use were unrelated to heroin use.
      Longer periods spent in RR were associated with declines in the use of all other
      drug classes, with MT associated with declines in other opioid and alcohol use.
      CONCLUSIONS: There was no evidence for drug substitution in the face of reduced
      heroin use in this cohort of treatment seekers. The fear that a successful
      reduction in heroin use amongst treatment seekers will precipitate an increase in
      the use of other drugs appears ill-founded.

PMID- 16580794
TI  - Identification and characterization of a novel bovine oocyte-specific secreted
      protein gene.
AB  - The oocyte transcriptome and proteome largely remain a mystery and the important
      roles of these genes, especially in the bovine, are poorly understood. To better
      understand specific developmental roles of the bovine oocyte, we sought to
      characterize a novel oocyte gene. We have sequenced the full-length mRNAs of
      bovine oocyte-secreted protein 1 (OOSP1) and discovered two splice variants,
      namely OOSP1_v1 (variant 1) and OOSP1_v2 (variant 2). The OOSP1 gene is located
      on chromosome 15 and is composed of 5 exons, which span over nearly 7.9 kb.
      Bovine OOSP1_v1 encodes a predicted protein of 163 aa in length that shares amino
      acid identity with mouse OOSP1, it also bears a putative signal peptide and is
      probably glycosylated. Bovine OOSP1_v2 protein bears the same signal peptide as
      OOSP1_v1 but due to the skipping of exon 2 that introduces a frameshift, it is
      only 35 aa in length. Expression analysis of both OOSP1 transcripts showed that
      this gene is exclusively expressed in oocytes, contrasting with the mouse where
      Oosp1 is also expressed in the spleen and liver. OOSP1_v1 and OOSP1_v2 mRNA
      expression profiling using real-time PCR revealed that their mRNA levels were
      high in germinal vesicle (GV) stage oocytes and gradually decreased until the
      blastocyst stage, at which time they were undetectable. For the first time, we
      have identified the bovine OOSP1 gene as being one of the few known oocyte
      specific markers.

PMID- 16580796
TI  - Comparative evaluation of two decontamination methods for the isolation of
      Mycobacterium avium subspecies paratuberculosis from faecal slurry and sewage.
AB  - Faecal slurry of animal origin from sale yards and raw sewage from a sewage
      treatment plant were sampled for the radiometric culture over 5 months at
      approximately weekly intervals. Before the radiometric culture, samples were
      decontaminated using the double incubation method. One set of triplicate samples
      of slurry and sewage was decontaminated at 37 degrees C and the other set was
      decontaminated at 42 degrees C. M. a. paratuberculosis or its DNA was detected in
      seven of 45 cultures (15.6%) of slurry decontaminated at 37 degrees C and in 14
      of 39 cultures (35.9%) of slurry decontaminated at 42 degrees C. The
      contamination rates in cultures of slurry processed at 37 degrees C and 42
      degrees C were 82.2% and 69.2%, respectively. M. a. paratuberculosis DNA was also
      detected in one of 45 cultures (2.2%) of sewage decontaminated at 42 degrees C.
      The contamination rates in samples of sewage processed at 37 degrees C and 42
      degrees C were 84.4% and 4.4%, respectively. Results of this study warrant
      further investigations to evaluate the suitability of a decontamination method at
      42 degrees C for the isolation of M. a. paratuberculosis from faeces, tissues and
      milk.

PMID- 16580795
TI  - Thioredoxin system in obligate anaerobe Desulfovibrio desulfuricans:
      Identification and characterization of a novel thioredoxin 2.
AB  - Metal corroding sulfate reducing bacteria have been poorly characterized at
      molecular level due to difficulties pertaining to isolation and handling of
      anaerobes. We report here for the first time the presence and characterization of
      thioredoxin 2 in an obligate anaerobic dissimilatory sulfate reducing bacterium
      Desulfovibrio desulfuricans. In silico analysis of the D. desulfuricans genome
      revealed the presence of thioredoxin 1 (dstrx1), thioredoxin 2 (dstrx2) and
      thioredoxin reductase (dstrxR) genes. These genes were found to be actively
      expressed by the bacteria under the anaerobic growth conditions. We have
      overexpressed the anaerobic thioredoxin genes in E. coli to produce functionally
      active recombinant proteins. Recombinant DsTrxR recognized both DsTrx1 and DsTrx2
      as its substrate. Mutation studies revealed that the activity of DsTrx2 can be
      completely abolished with a single amino acid mutation (C69A) in the signature
      motif 'WCGPC'. Furthermore, the N-terminal domain of DsTrx2 containing two extra
      CXXC motifs was found to have a negative regulation on its biochemical activity.
      In conclusion, we have shown the presence of thioredoxin 2 for the first time in
      an obligate anaerobe which in this anaerobe may be required for its survival
      under either oxidative stress conditions or metal ion hemostasis.

PMID- 16580782
TI  - N-cadherin mediates nitric oxide-induced neurogenesis in young and retired
      breeder neurospheres.
AB  - Neurogenesis may contribute to functional recovery after neural injury. Nitric
      oxide donors such as DETA-NONOate promote functional recovery after stroke.
      However, the mechanisms underlying functional improvement have not been
      ascertained. We therefore investigated the effects of DETA-NONOate on neural
      progenitor/stem cell neurospheres derived from the subventricular zone from young
      and retired breeder rat brain. Subventricular zone cells were dissociated from
      normal young adult male Wistar rats (2-3 months old) and retired breeder rats (14
      months old), treated with or without DETA-NONOate. Subventricular zone
      neurosphere formation, proliferation, telomerase activity, and Neurogenin 1 mRNA
      expression were significantly decreased and glial fibrillary acidic protein
      expression was significantly increased in subventricular zone neurospheres from
      retired breeder rats compared with young rats. Treatment of neurospheres with
      DETA-NONOate significantly decreased neurosphere formation and telomerase
      activity, and promoted neuronal differentiation and neurite outgrowth
      concomitantly with increased N-cadherin and beta-catenin mRNA expression in both
      young and old neurospheres. DETA-NONOate selectively increased Neurogenin 1 and
      decreased glial fibrillary acidic protein mRNA expression in retired breeder
      neurospheres. N-cadherin significantly increased Neurogenin 1 mRNA expression in
      young and old neurospheres. Anti-N-cadherin reversed DETA-NONOate-induced
      neurosphere adhesion, neuronal differentiation, neurite outgrowth, and beta
      catenin mRNA expression. Our data indicate that age has a potent effect on the
      characteristics of subventricular zone neurospheres; neurospheres from young rats
      show significantly higher formation, proliferation and telomerase activity than
      older neurospheres. In contrast, older neurospheres exhibit significantly
      increased glial differentiation than young neurospheres. DETA-NONOate promotes
      neuronal differentiation and neurite outgrowth in both young and older
      neurospheres. The molecular mechanisms associated with the DETA-NONOate
      modulation of neurospheres from young and older animals as well age dependent
      effects of neurospheres appear to be controlled by N-cadherin and beta-catenin
      gene expression, which subsequently regulates the neuronal differentiating factor
      Neurogenin expression in both young and old neural progenitor cells.

PMID- 16580801
TI  - [A case of tuberculous otitis media associated with meningoencephalitis in the
      Bangui paediatric institution (Central African Republic)].
AB  - The authors report a case of fatal tuberculous meningoencephalitis following
      chronic bilateral otitis media in a child. Mycobacterium tuberculosis was
      identified in the CSF and in the otitis secretions. There were no pulmonary
      tuberculosis signs, thus the tuberculous otitis was considered as primary. In
      high tuberculosis endemic areas like Central African Republic it is important to
      consider tuberculosis, in chronic otitis media resistant to non specific therapy,
      and to reinforce the immunization programs for children.

PMID- 16580797
TI  - Elaboration and characterization of thiolated chitosan-coated acrylic
      nanoparticles.
AB  - The aim of the present work was to investigate the use of thiolated chitosan in
      the development of polysaccharide-coated nanoparticles in order to confer
      specific functionality to the system. After chemical modification of commercial
      and hydrolysed chitosan (400,000 and 9400 g/mol respectively), thiolated
      chitosans were used to elaborate particles in the nano-range. They were
      characterized in terms of size and surface charge measurement. Both analysis
      showed nanoparticles of mean hydrodynamic diameter around 200 nm and positive
      zeta potential values, indicating the presence of the cationic polysaccharide at
      the nanoparticle surface. Moreover, the Ellman's reaction was used to demonstrate
      the presence of thiol groups at the particle surface. The observation of
      nanoparticles by scanning electronic microscopy (SEM) showed spherical
      nanoparticles for all formulations. This new system, combining both the
      advantages of thiolated polymers and colloidal particles can be proposed as an
      original drug carrier system for mucosal delivery of biotechnology products.

PMID- 16580800
TI  - Matrix degradation inhibitory effect of Schisandra fructus on human articular
      cartilage and chondrocytes.
AB  - The purpose of this study is to assess the protective effects exerted by
      Schisandra fructus (SF) on hyaluronidase (HAase) and the recombinant human
      interleukin-1beta (IL-1beta) induced matrix degradation in human articular
      cartilage and chondrocytes. The effect of SF on the matrix gene expression of
      immortalized chondrocyte cell line C-28/I2 treated with HAase was investigated
      using a reverse transcription polymerase chain reaction (RT-PCR). In addition,
      the effects of SFEA on HAase and IL-1beta induced matrix degradation in human
      articular cartilage were assessed using a staining method, and the quantity of
      glycosaminoglycan (GAG) degraded was calculated from the cultured media. In HAase
      treatment group, the released GAGs content increased significantly to 15.8+/-0.7
      microg, compared with control levels (5.0+/-0.2 microg), whereas co-treatment
      with SFEA (100 microg/ml) reduced the GAG release to 10.8+/-0.7 microg (P<0.05).
      Also, in the group treated only with IL-1beta (11.9+/-0.3 microg), the amount of
      released GAG increased significantly compared to the control (7.9+/-0.1 microg)
      and the SFEA-treated group (7.8+/-0.4 microg). SFEA at 100 microg/ml inhibited PG
      degradation (9.0+/-0.5 microg, P<0.05). However, no concentration-dependent
      increases in inhibitory activity were observed. Therefore, since SFEA treatment
      resulted in no pathological impact on either the chondrocytes or cartilage, we
      suggest that SF can be safely used as an effective material for the prevention of
      proteoglycan (PG) degradation.

PMID- 16580799
TI  - Preventive and curative effect of Lygodium flexuosum (L.) Sw. on carbon
      tetrachloride induced hepatic fibrosis in rats.
AB  - The preventive and curative effect of Lygodium flexuosum on experimentally
      induced hepatic fibrosis by carbon tetrachloride (CCl(4)) was evaluated in rats.
      Hepatic fibrosis was induced in male Wistar rats by CCl(4) administration (150
      microL/100g rat weight, oral) twice a week for 10 weeks. In preventive treatment
      daily doses of Lygodium flexuosum n-hexane extract (200 mg/kg, p.o) was
      administered for 10 weeks. In curative treatment Lygodium flexuosum extract (200
      mg/kg, p.o) was given for 2 weeks after the establishment of fibrosis for 10
      weeks. Treatment with CCl(4) caused a significant decrease in body and liver
      weight. Lygodium flexuosum n-hexane extract prevented or reversed the decline in
      body and liver weight. Treatment with the extract prevented or restored the
      elevation of serum AST, ALT and LDH levels. Lygodium flexuosum treatment
      remarkably prevented or reversed an increase in liver hydroxyproline content in
      chronically treated rats. Histopathological changes of hepatic lesions induced by
      CCl(4) were significantly (p < or = 0.05) improved by treatment with Lygodium
      flexuosum. These results support that Lygodium flexuosum exerts effective
      protection in carbon tetrachloride induced hepatic fibrosis in rats.

PMID- 16580798
TI  - Transgene correction maintains normal cochlear structure and function in 6-month
      old Myo15a mutant mice.
AB  - The shaker2 (sh2) mouse is a murine model for human non-syndromic deafness DFNB3.
      The mice have abnormal circling behavior suggesting a balanced disorder, and
      profound deafness. The insertion of a bacterial artificial chromosome (BAC)
      transgene containing the Myo15a gene into sh2/sh2 zygotes confers hearing
      capability and abolishes the circling behavior in 1-month-old transgenic animals.
      In this study, we investigated both the hearing and the morphology of the cochlea
      in Myo15a mutants carrying this BAC transgene at two, four, or six months of age.
      The hearing threshold of these mice is normal, with no physiologically
      significant differences compared to age-matched heterozygous sh2J mice (with or
      without the BAC transgene). In six-month-old transgenic mice with the BAC, the
      morphology of hair cells in the apical and upper basal turns of the cochlea is
      normal. Hair cells of lower basal turn, however, were missing in some mutant
      animals. This study demonstrates that BAC transgene correction cannot only
      maintain normal morphology but also confer stable hearing function in Myo15a
      mutant mice for as long as 6 months. In addition, excess Myo15a expression has no
      physiologically significant protective or deleterious effects on hearing of
      normal mice, suggesting that the dosage of Myo15a may not be problematic for gene
      therapy.

PMID- 16580806
TI  - CT features of primary epiploic appendagitis.
AB  - OBJECTIVE: The aim of this study is to describe the computed tomography (CT)
      findings of primary epiploic appendagitis (PEA). METHODS: We reviewed the
      clinical records and CT images of 14 consecutive patients in Singapore who
      presented with acute abdominal pain from July 2000 to April 2004 and had
      radiological signs of PEA. RESULTS: Hyperattenuated ring with adjacent fat
      stranding was present in all the patients. The central high attenuation dot was
      seen in 42.9% (6/14) of the patients. We observed a lobulated fatty mass in 21.4%
      (3/14) of our patients. All patients recovered during clinical follow-up.
      CONCLUSIONS: We believe the lobulated appearance of PEA is due to two or more,
      contiguous infarcted epiploic appendages lying in close proximity. This
      appearance further aids in the diagnosis of PEA and helps differentiates the
      condition from omental infarction. Recognizing the CT signs of PEA should allow a
      confident diagnosis and avoid unnecessary surgery.

PMID- 16580802
TI  - [Outpatient parenteral antimicrobial therapy (OPAT) in bone and joint
      infections].
AB  - The medical treatment of many bone and joint infections (including chronic
      osteomyelitis, prosthetic joint infection, and septic arthritis) requires
      prolonged intravenous antimicrobial therapy. For some patients, this treatment
      could be administered outside the hospital in a program that offers outpatient
      parenteral antimicrobial therapy (OPAT). In France, we have no registry of
      patients receiving OPAT. Initiation of this program requires specific criteria
      based on a patient evaluation and selection, and an interdisciplinary team of
      professionals committed to high-quality patient care. Various vascular access
      devices and infusion pump therapy are used to administer OPAT. The most common
      parenteral agents for OPAT are beta-lactams and glycopeptids (specifically
      vancomycin). Antimicrobial courses are stopped prematurely in 3 to 10% of the
      cases because of an adverse reaction or vascular access complications. Several
      published studies demonstrate the effectiveness of OPAT and higher patient
      satisfaction than hospital care. In addition, OPAT is clearly more cost-effective
      than intravenous therapy provided in the hospital setting. Some diagnoses, such
      as cellulites, community-acquired pneumonia, and endocarditis may be managed with
      OPAT.

PMID- 16580803
TI  - [Unusual presentation of visceral leishmaniasis in an immunocompetent patient].
AB  - Visceral leishmaniasis due to Leishmania infantum is endemic in Tunisia. The
      incidence in adult patients has increased in recent years; but most of these
      patients are not HIV positive as in other Mediterranean countries where all the
      cases are associated with HIV. We present the case of a woman with symptoms
      suggestive of leishmaniasis but whose bone marrow was sterile and whose
      serological tests for Leishmania spp. were negative. For this patient, the
      parasite was only detected in a routine duodenal biopsy. There are few reports of
      visceral leishmaniasis cases diagnosed by duodenal biopsy and almost all patients
      were HIV positive in that case. Thus it seems interesting to perform a duodenal
      biopsy in case of a difficult diagnostic even in the absence of gastrointestinal
      symptoms and/or HIV infection.

PMID- 16580805
TI  - Estradiol prevents release of cytochrome c from mitochondria and inhibits
      ischemia-induced apoptosis in perfused heart.
AB  - The study investigated whether estradiol can prevent release of cytochrome c from
      mitochondria and induction of apoptosis after 30 and 60 min stop-flow heart
      ischemia in Langendorff-perfused female rat hearts. Pre-perfusion of hearts with
      100 nM 17beta-estradiol prevented the loss of cytochrome c from mitochondria, its
      accumulation in cytosol, and inhibition of respiration during ischemia. Estradiol
      strongly reduced activation of caspase-3-like activity and decreased DNA strand
      breaks in the nuclei of cardiomyocytes (measured by TUNEL staining). The results
      show that 17beta-estradiol prevents the ischemia-induced release of cytochrome c
      from mitochondria, subsequent inhibition of mitochondrial respiration, and
      inhibits caspase activation and apoptosis. Therefore, inhibition of the
      intrinsic, mitochondria-mediated apoptotic pathway may be one of the mechanisms
      by which estrogens protect the heart against ischemic damage.

PMID- 16580807
TI  - Newly synthesized tetraoxa-diaza crown ether derivatives versus commercialized
      crown ethers in the separation of positional isomers with capillary
      electrophoresis.
AB  - Three new tetraoxa-diaza derivatives of 1,4,10,13-tetraoxa-7,16-diazacyclo
      octadecane (R-1, R-2 and R-3) and three commercially available crown ethers, 18
      crown-6 (18C6), (+)-18-crown-6-tetracarboxilic acid (18C6H4) and 1,4,10,13
      tetraoxa-7,16-diazacyclo-octadecane, were investigated to separate the positional
      isomers of aminophenol, aminobenzoic acid and aminocresol. The running
      electrolyte, in which the crown ethers were dissolved, was a 50 mM Tris solution
      adjusted to pH 2.0 with hydrochloric acid. Using 50 mM H3PO4 buffer, whose pH was
      adjusted to 2.0 with Tris, or only hydrochloric acid solution with the same pH,
      did not allow good separations for the tested components. The effect of the crown
      ether concentration on the separation of the 11 positional isomers was studied in
      the concentration range of 10-50 mM. The best separations were achieved using the
      18C6 and the 18C6H4 crown ethers: 9 isomers out of 11 could be separated within
      one run. The m- and p-aminophenol isomers could not be separated under the
      investigated experimental conditions. The newly synthesized tetraoxa-diaza crown
      ether derivatives were only found suitable for the separation of aminobenzoic
      acid positional isomers. The macrocyclic ring of the tetraoxa-diaza crown ethers
      was not able to form a stable inclusion complex with the tested positional
      isomers. Consequently, the aminophenol and aminocresol isomers were not
      separated, the isomers migrated with the same or very similar velocities.

PMID- 16580808
TI  - Poor results after surgery for bronchioloalveolar carcinoma.
AB  - BACKGROUND: Bronchioloalveolar carcinoma (BAC) is suggested to be less aggressive
      than other types of lung cancer. To assess the option of treatment modification,
      actual outcome data were studied and compared with results for other types of
      lung cancer. METHOD: Retrospective analysis of all consecutive patients who
      underwent resection for stage I lung cancer in our hospital. For 18 BAC cases,
      histological specimens were re-evaluated and in three cases diagnosis was
      revised. RESULTS: In the period 1989 through 2000, 15 patients with BAC and 260
      patients with other tumour types underwent surgery in our hospital. Five-year
      survival rates were 24 and 53%, respectively, (p = 0.01). CONCLUSIONS: Given the
      poor results after standard surgery, parenchyma-sparing operations do not seem
      justified in patients with invasive BAC.

PMID- 16580804
TI  - HSF expression in skeletal muscle during myogenesis: implications for failed
      regeneration in old mice.
AB  - The ability of muscles of old mice to recover force generation following
      substantial damage is severely impaired, particularly during the late phase of
      regeneration. This inability to recover successfully may be associated with the
      attenuated ability of muscles of old mice to produce heat shock proteins (HSPs)
      in response to stress since muscles of old mice overexpressing HSP70 recover
      successfully following damage. The capacity of mature mammalian skeletal muscle
      to regenerate following damage is due to the presence of undifferentiated
      mononuclear myogenic precursor cells (satellite cells) at the periphery of mature
      skeletal muscle fibres. HSP expression is under the primary transcriptional
      control of heat shock factors 1 and 2 (HSF1 and HSF2). The aim of this study was
      to examine the expression of heat shock factors 1 and 2 by western blotting in
      mouse-derived C2C12 myoblasts as an experimental model system for investigating
      skeletal muscle regeneration. Data demonstrated that the HSF2 content of myotubes
      was significantly increased during the early stages of regeneration. In contrast,
      the HSF1 content of myotubes remained relatively low until late during
      regeneration. Thus, abnormal activation of HSF1 may play a role in the defective
      regeneration seen in muscles of old mice.

PMID- 16580809
TI  - Clinico-pathological features of cystic pancreatic endocrine neoplasms and a
      comparison with their solid counterparts.
AB  - AIM: Pancreatic endocrine neoplasms (PENs) may occasionally manifest as cystic
      lesions of the pancreas. The aim of this study is to report our experience with
      cystic PENs and to compare their clinico-pathological features with their solid
      counterparts. MATERIALS AND METHODS: From 1990 to 2004, 38 patients with PENs
      were reviewed. Six of these tumours appeared on radiological imaging as a cystic
      lesion of the pancreas. RESULTS: Of the 38 patients with a PEN, 21 of the
      patients were female and with a median age of 54.5 (range, 33-83) years. Sixteen
      patients had functional endocrine tumours of which insulinoma was the most
      common. The six patients with cystic PEN had a median age of 55.5 (range, 41-70)
      years and half were female. Cystic PENs were significantly larger [48 (range, 25
      170) mm vs 19 (range, 3-120) mm, P = 0.013] and were less likely to be benign (0
      vs 50%, P = 0.017) compared to their solid counterparts. There was no difference
      between cystic and solid PENs in terms of age, sex, presence of symptoms,
      proportion of functioning tumours and location of tumours within the pancreas.
      CONCLUSION: Cystic PENs share many clinico-pathological features with solid PENs.
      These differ only in the cystic appearance and tend to be of a larger size.
      Hence, these findings suggest that cystic and solid PENs are unlikely to be
      distinct pathological entities but are likely to be morphological variants of the
      same entity.

PMID- 16580810
TI  - Reasons for failure to identify positive sentinel nodes in breast cancer patients
      with significant nodal involvement.
AB  - AIM: To analyse causes of failure of sentinel node (SN) procedures in breast
      cancer patients and assess the role of pre-operative ultrasound examination of
      the axilla. METHODS: In 138 consecutive clinically node negative breast cancer
      patients with the primary tumour in situ a SN procedure with radiolabeled colloid
      and blue dye was performed. Radioactivity in the SN was scored as inadequate or
      adequate. The axillary lymph node dissection scored for number of involved nodes
      and presence of extranodal growth. RESULTS: In 53/138 patients, the SN was
      positive for tumour. Full axillary node dissection revealed that 58/138 were node
      positive. So in five patients the SN failed to predict true nodal status. In 3/5,
      the radioactive ratio (SN vs background) was inadequate. All were found to have
      extensive nodal involvement. The radioactivity ratio was inadequate in 37/138
      patients. This ratio was inadequate in 10 of 15 patients with > or =4 positive
      nodes and 27 of 123 in patients with 0-3 positive nodes (p < 0.001). If
      extranodal growth was present the radioactive ratio was inadequate in 13 of 18
      patients, whilst this was only the case in 24 of 120 patients without extranodal
      growth or metastases (p < 0.001). Ultrasound (US) examination and US-guided FNAC
      was able to pre-operatively identify 16 of the 26 patients with four or more
      metastases in the axilla. CONCLUSIONS: Extensive nodal involvement is an
      important cause of failure of the sentinel node biopsy. Pre-operative ultrasound
      examination of the axilla can avoid this in almost two thirds of these patients.

PMID- 16580811
TI  - Resection margin in patients undergoing hepatectomy for colorectal liver
      metastasis: a critical appraisal of the 1cm rule.
AB  - AIM: We undertook this study to evaluate the influence of resection margin
      distance from metastases on survival and post-operative disease recurrence after
      hepatectomy for colorectal liver metastasis. METHODS: Between January 1993 and
      December 2001, 293 consecutive patients underwent primary liver resection for
      colorectal metastasis. Clinical, pathological and outcome data were analysed
      using a prospectively collected database. Cases were stratified into those with
      involved and non-involved resection margins. Different non-involved margin widths
      were analysed against survival, recurrence rate and pattern (hepatic, extra
      hepatic) of recurrence. RESULTS: The 1, 3, 5 and 10 years actuarial survival
      rates were 82, 58, 44 and 36%, respectively. The median survival was 46 months.
      The histological liver resection margin involvement was a significant predictor
      of survival and disease free survival after surgery. One, two, five and 10
      millimetres disease free resection margin widths were found not to be significant
      in influencing patients' survival or recurrence rate. CONCLUSION: A positive
      hepatic resection margin was associated with a higher incidence of post-operative
      recurrence and lower survival rate. The width of the resection margin did not
      influence the post-operative recurrence rate or pattern of recurrence. The '1 cm
      rule' should be abandoned.

PMID- 16580812
TI  - [Request of epidural analgesia by women and obstetrical teams in four French
      areas. Part I: Request for analgesia].
AB  - OBJECTIVE: Epidural analgesia (EA) is widely used in France to treat the labour
      pain. The aim of this study was to evaluate and analyse the reasons of EA
      requirements by parturients and obstetricians. STUDY DESIGN: An epidemiological
      survey was sent in all maternity units of four French areas. PATIENTS AND
      METHODS: Forty-eight of the 84 maternity units entered the study. In each centre,
      25 patients fulfilled the questionnaire and the medical team fulfilled a
      questionnaire about the organisation of the ward. Demands of EA by parturients
      during pregnancy, labour and for the next delivery were recorded, and also the
      offer of EA by midwives and the possibility to move in an other town to obtain an
      EA. Student t-test, chi2 test and logistic regression model were used as
      requested. p<0.05 was considered as significant. RESULTS: One thousand one
      hundred forty-two women entered the study. During pregnancy 79% of women asked
      for an EA, they were 72% during labour. Factors influencing the request of an EA
      were parity, educational level, pain, preanaesthetic evaluation and the size and
      the kind of maternity unit (university, public or private hospital). During
      labour, the request of an EA was more frequent when anaesthesiologists were on
      call in the hospital (77.7 vs 66.7%, p<0.001). Midwives offered EA to 69% of
      women. For the next delivery 79.9% of women hoped an EA, the factors of this new
      request were parity, pain during this labour and EA during this labour; 42.8%
      would be ready to move in an other town to obtain an EA. The medical indications
      for EA occurred in 1.8% of patients. DISCUSSION: The request for EA mainly comes
      from women. Probably, in France, the request for EA will not diminish in the
      future. Analgesia networks could be considered.

PMID- 16580813
TI  - Validation of a prediction model for estimating serum concentrations of chemicals
      which are equivalent to toxic concentrations in vitro.
AB  - The objective of the present study was to evaluate the validity of a recently
      developed extrapolation model for the prediction of concentrations of chemicals
      in serum which are equivalent to in vitro effective nominal concentrations.
      Necessary input data are in vitro toxic concentrations and distribution relevant
      system and substance specific parameters, e.g. lipid volume fractions and albumin
      concentrations, octanol/water partition coefficients and specific binding to
      albumin. It was investigated whether the influence of human and bovine serum,
      respectively, on nominal cytotoxic potencies (EC(50)-values) of selected
      chemicals in vitro can be properly predicted using this algorithm. Cytotoxicity
      was determined as growth inhibition of proliferating Balb/c 3T3 cells after
      exposure for 72 h. Concentration-effect relationships were measured in the
      presence of 2% foetal bovine serum (FBS) and, additionally, 18% FBS or human
      serum (HS), or 1% (w/v) bovine (BSA) or human (HSA) albumin, respectively.
      Addition of HSA and BSA increased the EC(50)-values of the different chemicals by
      factors of 2.1 - 22 and 1.7 - 29, respectively. From these measurements values
      for the specific binding of the test compounds to BSA and HSA were derived.
      Addition of 18% HS increased the EC(50)-values by factors between 4.2 and 52,
      while addition of 18% FBS resulted only in 1.5 - 10.4-fold increases. A
      comparison of experimentally determined and calculated EC(50)-values revealed
      that the differing influence of human and bovine serum was quite well predicted
      by the extrapolation model. Deviations did not exceed the factor 3 and were in
      most cases lower than 2. It is concluded that the extrapolation model is quite
      well suited to predict equivalent concentrations in serum from in vitro effective
      concentrations.

PMID- 16580814
TI  - Cytokines in schizophrenia and the effects of antipsychotic drugs.
AB  - Growing evidence suggests that the immune, endocrine, and nervous systems
      interact with each other through cytokines, hormones, and neurotransmitters. The
      activation of the cytokine systems may be involved in the neuropathological
      changes occurring in the central nervous system (CNS) of schizophrenic patients.
      Numerous studies report that treatment with antipsychotic drugs affects the
      cytokine network. Hence, it is plausible that the influence of antipsychotics on
      the cytokine systems may be responsible for their clinical efficacy in
      schizophrenia. This article reviews current data on the cytokine-modulating
      potential of antipsychotic drugs. First, basic information on the cytokine
      networks with special reference to their role in the CNS as well as an up-to-date
      knowledge of the cytokine alterations in schizophrenia is outlined. Second, the
      hitherto published studies on the influence of antipsychotics on the cytokine
      system are reviewed. Third, the possible mechanisms underlying antipsychotics'
      potential to influence the cytokine networks and the most relevant aspects of
      this activity are discussed. Finally, limitations of the presented studies and
      prospects of future research are delineated.

PMID- 16580815
TI  - Trainable fusion rules. I. Large sample size case.
AB  - A wide selection of standard statistical pattern classification algorithms can be
      applied as trainable fusion rules while designing neural network ensembles. A
      focus of the present two-part paper is finite sample effects: the complexity of
      base classifiers and fusion rules; the type of outputs provided by experts to the
      fusion rule; non-linearity of the fusion rule; degradation of experts and the
      fusion rule due to the lack of information in the design set; the adaptation of
      base classifiers to training set size, etc. In the first part of this paper, we
      consider arguments for utilizing continuous outputs of base classifiers versus
      categorical outputs and conclude: if one succeeds in having a small number of
      expert networks working perfectly in different parts of the input feature space,
      then crisp outputs may be preferable over continuous outputs. Afterwards, we
      oppose fixed fusion rules versus trainable ones and demonstrate situations where
      weighted average fusion can outperform simple average fusion. We present a review
      of statistical classification rules, paying special attention to these linear and
      non-linear rules, which are employed rarely but, according to our opinion, could
      be useful in neural network ensembles. We consider ideal and sample-based oracle
      decision rules and illustrate characteristic features of diverse fusion rules by
      considering an artificial two-dimensional (2D) example where the base classifiers
      perform well in different regions of input feature space.

PMID- 16580816
TI  - Primary malignant schwannoma of the cervical plexus with melanocytic
      differentiation.
AB  - Primary malignant schwannomas are rare neoplasms of nerve sheath origin,
      especially in the location of the head and neck where few cases are described in
      the literature. These tumours may pose a diagnostic dilemma in the work-up of a
      neck mass. The case presented here is of a malignant schwannoma that originated
      in the cervical plexus with the rare histological feature of melanocytic
      differentiation. Histopathological examination with immunostaining techniques is
      essential for the diagnosis of these tumours. The management of these neoplasms
      is still controversial, although the treatment of choice is radical surgical
      excision of the lesion. The role of postoperative radiotherapy or chemotherapy is
      not clear, although some authors recommend its use to prevent local recurrence,
      for unresectable recurrent tumours or in cases of distant metastases.

PMID- 16580817
TI  - Growth characteristics of large mandibular ameloblastomas: report of 5 cases with
      implications for the approach to surgery.
AB  - The aim of this study was to establish surgical guidelines based on the growth
      pattern of ameloblastomas in relation to the possible infiltration of the
      cortical bone, the inferior alveolar nerve, the periosteal layer and the
      surrounding soft tissues. Five male patients with voluminous mandibular
      ameloblastomas were treated by means of radical surgery. Ameloblastomas showed an
      invasive growth pattern in the cancellous bone with small tumour nests at a
      maximum distance of 5mm away from the bulk of the tumour. Expansive and invasive
      growth in the Haversian canals was observed. There was no invasion of the
      inferior alveolar nerve. The mucoperiosteal layer was invaded but not perforated.
      No invasion was observed in the surrounding soft tissues of the periosteum and in
      the skin tissue. A local resection with a surgical margin of spongious bone of
      1cm is suggested. When the tumour is radiologically closer than 1cm to the
      inferior border of the mandible, a continuity resection is mandatory. A
      conservative approach concerning the inferior alveolar nerve is suggested.
      Removal of an excess of perimandibular soft tissue is not indicated. The
      overlying attached mucosal surface should however be excised together with the
      underlying bone.

PMID- 16580818
TI  - Attention for movement production: Abnormal profiles in schizophrenia.

PMID- 16580819
TI  - The demicellization of alkyltrimethylammonium bromides in 0.1 M sodium chloride
      solution studied by isothermal titration calorimetry.
AB  - The demicellization of the cationic detergents dodecyltrimethylammonium bromide,
      tetradecyltrimetylammonium bromide, and cetyltrimethylammonium bromide was
      studied at temperatures between 20 and 60 degrees C in 0.1 M NaCl (pH 6.4) using
      isothermal titration calorimetry (ITC). We determined the critical micellization
      concentration (cmc) of the cationic detergents which show a minimum at
      temperatures between 20 and 34 degrees C. In accordance with the lengthening of
      the hydrophobic tail of the detergents the cmc decreases with increasing alkyl
      chain length. The thermodynamic parameters describing the changes of enthalpy
      (DeltaH(demic)), the changes of entropy (DeltaS(demic)) and the Gibbs free energy
      change (DeltaG(demic)) for demicellization were first obtained using the
      pseudophase-separation model. The aggregation number n at the cmc as well as the
      demicellization enthalpy, entropy and Gibbs free energy change were also
      calculated using a simulation based on the mass-action model. Furthermore, we
      investigated the demicellization of CTAB in deionized water in comparison to
      demicellization in sodium chloride solution to determine the influence of counter
      ion binding on the demicellization.

PMID- 16580821
TI  - Adriamycin-induced oxidative stress, activation of MAP kinases and apoptosis in
      isolated cardiomyocytes.
AB  - BACKGROUND: Adriamycin (ADR) induced heart failure is associated with an increase
      in oxidative stress and apoptosis. Changes due to ADR in mitogen-activated
      protein kinases (ERK1/2 and p38 MAPKs), pro- and anti-apoptotic proteins (Bax and
      Bcl-xl) and apoptosis were examined in isolated adult rat cardiomyocytes.
      METHODS: Isolated adult rat cardiomyocytes were exposed to different
      concentrations of ADR (0.1, 1 and 10mumol/L) and analyzed at different post
      treatment durations. Antioxidant, trolox (20mumol/L) was used to determine
      involvement of oxidative stress on these changes. RESULTS: Total ERK1/2 and p38
      did not show any significant change. However, phosphorylated ERK1/2 showed a
      rapid increase (497%) after 5min of ADR treatment, peaking (610%) at 10min
      followed by a decline to submaximal levels at 30min (280%) and 60min (247%).
      Phosphorylated p38 showed no changes until after 30min, peaking (284%) at 1h,
      followed by a small decline at 2h. These changes were found to be dose-dependent
      (0.1, 1 and 10mumol/L of ADR). Adriamycin induced apoptosis was confirmed by
      Hoechst staining. The ratio of Bax/Bcl-xl increased in a dose-dependent manner.
      At 10mumol/L, this ratio increased to a maximum at 1h, remained steady at the
      level for up to 12h, followed by a decline below the base line at 24h.
      Antioxidant, trolox modulated the ADR-induced increase in phosphorylation of
      ERK1/2 and p38 MAPKs as well as in the ratio of Bax/Bcl-xl. CONCLUSION: It is
      suggested that ADR activates MAP kinases, followed by an activation of pro
      apoptotic protein Bax which results in cardiomyocyte apoptosis and these effects
      appear to be mediated by ADR-induced oxidative stress.

PMID- 16580820
TI  - Physico-chemical lyophilization behavior of mannitol, human serum albumin
      formulations.
AB  - The lyophilization behavior is influenced by the presence of salts. The impact of
      NaCl on drying-time and the morphology after lyophilization was studied for
      formulations with mannitol and HSA, using different freezing-protocols. The
      drying-process was monitored by thermocouples and microbalance technique. Karl
      Fischer titration, DSC, XRD, SEM and turbiditimetry and HP-SEC were used to study
      the products after lyophilization and 6 months storage at 2-8 degrees C, 25
      degrees C/60% RH and 40 degrees C/75% RH. NaCl decreases the drying-time of
      mannitol-HSA formulations, indicating morphological changes, which was confirmed
      by XRD and SEM. Without NaCl exclusively delta-mannitol is formed, which remains
      physico-chemically stable upon storage for 6 months. With increasing NaCl
      concentrations more beta-mannitol and finally amorphous products are formed,
      whereby the freezing-protocol determines how much NaCl is needed to achieve an
      amorphous product. Upon storage, the amorphous state cannot be preserved and
      mannitol and NaCl crystallize, which can damage proteins in the formulations.
      However, regarding the stability of HSA in the lyophilized products, monitored by
      turbidimetry and HP-SEC, the addition of NaCl can prevent increases in turbidity
      upon storage. Here the benefit of NaCl on HSA stability outbalances the potential
      drawbacks that morphological changes, like crystallization impose on protein
      stability in the lyophilized products.

PMID- 16580822
TI  - [Dietary water intoxication: a preventable pathology].
AB  - CASE REPORT: The authors report the case of an infant presenting with status
      epilepticus, apneas and hypothermia, related to hyponatremia. The cause was water
      intoxication, secondary to feeding a dilute formula and free water. The parents
      were notoriously challenged by the care of their children. Such disorder could
      have been prevented. CONCLUSION: Dietary history may be key to the diagnosis of
      hyponatremia in children. Water intoxication of nutritional origin can be
      prevented.

PMID- 16580823
TI  - [Peritonitis as a first manifestation of Neisseria type C meningitis].
AB  - A 15-year-old boy was first referred for a clinical presentation of revealed
      peritonitis. Abdominal endoscopy showed normal appendix but the presence of
      purulent peritoneal fluid. Antibiotics were immediately administered. Ten hours
      later clinical signs of meningitis occurred, and lumbar puncture was performed.
      CSF bacterial meningitis characteristics were present but no bacteria was
      observed. However Neisseria meningitidis type C was detected by direct peritoneal
      fluid examination and by 24(th) hour blood culture. Peritoneal and the CSF fluid
      culture were negative, but DNA analysis from peritoneal fluid was positive.

PMID- 16580824
TI  - [Severe asthma due to an esophageal foreign body in a child].
AB  - A 4-year-old boy had infantile bronchial asthma resistant to treatment. He was
      referred for a febrile respiratory distress which led to the diagnosis of
      periesophagus mediastinis mass with erosion of both contiguous vertebral discs.
      The oesophagogram showed a foreign body in an esophageal diverticulum. After its
      extraction, all pulmonary symptoms disappeared.

PMID- 16580825
TI  - Gene expression profiling as novel tool in experimental asthma research.
AB  - With the advances achieved in decoding of the genetic structures of species and
      the novel possibilities of simultaneous measurements of the regulation of all
      genes of a given tissue, the last 10 years have seen a massive increase of our
      knowledge about genetic regulation of diseases. Additionally, the possibilities
      to control transcriptional processes within the cells will speed up the process
      of disentangling the various pathways leading to disease.

PMID- 16580826
TI  - Novel strategies of aerosolic pharmacotherapy.
AB  - The pulmonary administration of drugs plays a crucial role in the management of
      various respiratory and systemic diseases. While the cellular properties of
      airway epithelial cells offer a great potential to deliver drugs into the lungs
      or the circulation, only little is known about the exact transport pathways.
      Recently, the high-affinity proton-coupled drug and peptide transporter PEPT2 was
      identified in the human respiratory tract. The expression of transporter mRNA and
      protein was localized to the airway epithelium and alveolar type II pneumocytes.
      In addition, transport studies revealed transporter-mediated uptake of substrates
      into epithelial cells indicating that the transporter is the molecular basis for
      the transport of peptides and peptidomimetic drugs in pulmonary epithelial cells.
      Since genotype analysis revealed no significant differences amongst different
      transporter genotypes concerning expression and function, the transporter
      displays an interesting novel target for pulmonary delivery of drugs.

PMID- 16580827
TI  - Specific aspects of flow cytometric analysis of cells from the lung.
AB  - Flow cytometry represents a powerful method for the analysis of cell functions
      and has therefore been applied in all fields of biomedical research including
      respiratory research. Some specific aspects have to be considered when
      investigating cells from the lung that include preparation and analysis of cells
      from different lung compartments and problems evoking due to high
      autofluorescence of alveolar macrophages. The present short review discusses
      these issues and, in addition, gives an example for a recently developed
      application of flow cytometric analysis in the field of lung research that allows
      the differentiation between resident and newly infiltrated alveolar macrophages.

PMID- 16580828
TI  - Are mouse models of allergic asthma useful for testing novel therapeutics?
AB  - Experimental mouse allergic asthma is a reliable, clinically relevant facsimile
      of human disease. The focus here is to demonstrate that antigen-induced mouse
      allergic asthma is a useful model for testing novel therapeutics. Furthermore, it
      is especially crucial to treat mice during established disease, either during
      ongoing clinically manifest disease or to prevent disease relapses. In addition,
      our results indicate that lung Th2 resting memory cells are important targets for
      the treatment of allergic asthma.

PMID- 16580829
TI  - Biodegradation of corrosion inhibitors and their influence on petroleum product
      pipeline.
AB  - The present study enlightens the role of Bacillus cereus ACE4 on biodegradation
      of commercial corrosion inhibitors (CCI) and the corrosion process on API 5LX
      steel. Bacillus cereus ACE4, a dominant facultative aerobic species was
      identified by 16S rDNA sequence analysis, which was isolated from the corrosion
      products of refined diesel-transporting pipeline in North West India. The effect
      of CCI on the growth of bacterium and its corrosion inhibition efficiency were
      investigated. Corrosion inhibition efficiency was studied by rotating cage test
      and the nature of biodegradation of corrosion inhibitors was also analyzed. This
      isolate has the capacity to degrade the aromatic and aliphatic hydrocarbon
      present in the corrosion inhibitors. The degraded products of corrosion
      inhibitors and bacterial activity determine the electrochemical behavior of API
      5LX steel.

PMID- 16580830
TI  - Ethanol fermentation of mahula (Madhuca latifolia L.) flowers using free and
      immobilized yeast Saccharomyces cerevisiae.
AB  - There is a growing interest to find alternate bioresources for production of
      ethanol, apart from cane/sugar beet molasses and starchy crops like sweet
      sorghum, cassava and sweet potato. Mahula (Madhuca latifolia L.) is a forest tree
      abundantly available in the Indian subcontinent and its flowers are very rich in
      fermentable sugars (28.1-36.3 g 100 g(-1)). Batch fermentation of fresh and 12
      month-stored flowers with free (whole cells) and immobilized cells of
      Saccharomyces cerevisiae (strain CTCRI) was carried out in 2-l Erlenmeyer flasks.
      The ethanol yields were 193 and 148 g kg(-1) (using free cells) and 205 and 152 g
      kg(-1) (using immobilized cells) from fresh and 12-month-stored mahula flowers,
      respectively.

PMID- 16580832
TI  - Ultrastructural investigation of epithelial damage in asthmatic and non-asthmatic
      nasal polyps.
AB  - Nasal polyposis is a poorly understood chronic inflammatory disease often
      associated with asthma. As nasal polyps and asthma both are associated with
      massive eosinophil infiltration, they may share a common pathophysiological
      mechanism. Many genetic and autoimmune diseases may result from altered
      expression or function of cell adhesion molecules such as desmosomes. A
      transmission electron microscopical study was carried out on tissue from 15
      patients suffering from nasal polyps, to investigate if there are changes in
      desmosomes in nasal polyps from asthmatic and/or allergic patients versus non
      asthmatic versus non-allergic patients. In allergic patients the damage to
      columnar cells was more extensive than in non-allergic patients. Massive
      infiltration of eosinophils was observed in epithelium and connective tissue in
      all groups. No significant difference in thickness of the basal lamina was found
      between any of the groups. All patients had dilated capillaries in the connective
      tissue. The intercellular space between the epithelial cells was smallest in the
      asthmatic non-allergic group. The relative length of columnar cell or basal cell
      desmosomes was reduced in patients with asthma or allergy, compared to non
      allergic, non-asthmatic patients. Hence, there appears to be a weakness in the
      desmosomes in asthmatics and allergics. Epithelial shedding may play an important
      role in the pathophysiological process of a multifactorial disease such as
      asthma.

PMID- 16580833
TI  - Strength properties of concrete incorporating coal bottom ash and granulated
      blast furnace slag.
AB  - Coal bottom ash (CBA) and fly ash (FA) are by-products of thermal power plants.
      Granulated blast-furnace slag (GBFS) is developed during iron production in iron
      and steel plants. This research was conducted to evaluate the compressive
      strength property and some durability characteristics of concrete incorporating
      FA, CBA, and GBFS. FA is used as an effective partial cement replacement; CBA and
      GBFS are used as partial replacement for fine aggregate without grinding. Water
      absorption capacity, unit weight and compressive strengths in 7, 28, and 90-day
      ages were assessed experimentally. For these experiments, concrete specimens were
      produced in the laboratory in appropriate shapes. The samples are divided into
      two main categories: M1, which incorporated CBA and GBFS; and M2, which
      incorporated FA, CBA, and GBFS. Remarkable decreases are observed in compressive
      strength and water absorption capacity of the concrete; bulk density of the
      concrete is also decreased. It can be concluded that if the content of CBA and
      GBFS is limited to a reasonable amount, the small decreases in strength can be
      accepted for low strength concrete works.

PMID- 16580834
TI  - Addressing the operational problems in a composting and recycling plant.
AB  - The Istanbul composting and recycling plant, constructed in 2001, is one of the
      few composting plants in Turkey. During test operations of the plant, it was
      reported that the weight of the oversize materials (OM) above a 80-mm sieve was
      about 40% of the total incoming waste. They mainly consist of plastic bags that
      were full of garbage, which resulted in operational problems in the plant. In
      this paper, the composition of OM was determined and evaluated, particularly to
      find the economic losses in the plant. It was determined that approximately 58%
      of the OM transferred to the landfill area due to operational failures and
      interruptions could be used at the plant with improved operational conditions.
      Otherwise, the plant would realize an annual economic loss of about 640,800 US$.
      Compost quality in the plant has been satisfactory, but source separated
      collection, at least the separation of the wet from the dry fraction, is needed
      to increase the amount of compost and recovered materials.

PMID- 16580835
TI  - Electrochemical detection and characterization of proteins.
AB  - On-line detection of serum proteins is of clinical relevance, in detecting leaks
      and biofouling in hemofiltration equipment, biofilm growth on prosthetic devices,
      or hemolysis within a prosthetic or therapeutic device. Electrochemical impedance
      spectroscopy (EIS) and cyclic voltammetry (CV) were employed to detect and
      analyze micromolar concentrations of four globular proteins of clinical
      importance. CV testing showed that identification and quantification of each of
      these proteins was possible through analysis of current changes at specific
      potentials. Preliminary CV studies into the contamination of Bovine Serum Albumin
      with a microgram amount of one of the other three proteins illustrated that
      direct detection of the contaminant protein was possible. The analysis of the EIS
      data demonstrated that with increase in relative concentration of proteins, the
      amount of electroactive proteins adsorption at the interface increases, leading
      to increase in surface charge density and capacitance, especially for lower
      molecular weight proteins. The impedance data was used to determine the values of
      Gibbs adsorption energy, adsorption coefficients for the four proteins, and
      develop an equivalent circuit model for the protein-containing solutions.

PMID- 16580836
TI  - Cell invasion through basement membranes: an anchor of understanding.
AB  - To metastasize, cancer cells must acquire the ability to breach several basement
      membrane barriers. Cell invasions through basement membranes also occur during
      normal development and immune system function, enabling organ formation and cell
      dispersal. The mechanisms that cells use to cross basement membranes in vivo
      remain elusive. In cancer and development, these invasions occur in complex and
      inaccessible environments, which are difficult to study in vivo. Anchor-cell
      invasion in Caenorhabditis elegans is a simple, visually and experimentally
      accessible model of basement membrane invasion that is beginning to reveal a
      network of cellular and molecular control mechanisms that regulate the
      fundamental cellular process of invasion through basement membranes.

PMID- 16580837
TI  - Organization of postural responses following a rotational support surface
      perturbation, after TKA: sagittal plane rotations.
AB  - Proprioceptive dysfunction, related to osteoarthritis and total knee arthroplasty
      (TKA) may be related to changes in gait, and may result in balance impairment.
      This study examined the organization of postural responses to rotational support
      surface perturbations after TKA. Eight TKA patients and nine control participants
      volunteered. EMG was collected bilaterally from lower limb muscles. Kinematic
      data were collected using an OPTOTRAK system. The temporal pattern of muscle
      activation was preserved in both the surgical and sound limbs of the patient
      groups, while muscle activation amplitude was reduced. Knee joint angular
      displacement was reduced in both limbs among patients. COM displacement was not
      different. Patients demonstrated a different method in recovering posture control
      following a postural perturbation. Bilateral changes appear to reflect a
      simplification in the organization of the motor response, in response to the
      needs of the injured, or previously injured limb.

PMID- 16580838
TI  - A low-level activation technique for monitoring thermonuclear fusion plasma
      conditions.
AB  - Optimisation of the confinement and sustainability of a thermonuclear plasma
      requires methods to monitor processes in the plasma. In this work three materials
      were used as activation targets (Ti, MgF2 and a TiVAl compound). They were placed
      inside the joint European Torus (JET) vacuum chamber. Certain gamma-ray emitting
      radionuclides (7Be, 54Mn, 56Co, 57Co, 58Co and 46Sc) were measured using ultra
      low-level gamma-ray spectrometry in an underground laboratory 1-2 months after
      activation. They were found to arise from neutron activation of bulk sample
      material and surface contaminants sputtered from other Tokamak parts. Decision
      thresholds for some activation products were determined in order to aid in giving
      upper bounds for the flux of charged particles.

PMID- 16580839
TI  - Analysis of cadmium in food by multiple prompt gamma-ray spectroscopy.
AB  - The Cd concentration in food is a public concern related to the human health. In
      order to remove Cd-polluted food, the development and validation of a rapid and
      sensitive method of Cd analysis is required. By applying the multiple gamma-ray
      detection method to prompt gamma-ray analysis (PGA), the influence from nuclei
      which emit only one prompt gamma-ray at a time at every neutron capture reaction
      can be reduced, therefore the quantification limit of Cd is improved
      significantly. The limit of Cd contained in rice in the case of MPGA was
      evaluated, and under our proposed experimental conditions, it may be possible to
      quantify Cd content in rice to within 0.2 ppm in 10 min.

PMID- 16580840
TI  - B cells in the spotlight: innocent bystanders or major players in the
      pathogenesis of type 1 diabetes.
AB  - It has long been established that type 1 diabetes (T1D) is a T cell-mediated
      autoimmune disease, with CD4+ and CD8+ T cells being largely responsible for the
      destruction of beta cells within the pancreatic islets of Langerhans. Although
      autoantibodies specific for islet cell proteins are regularly detected in
      individuals with T1D and can be utilized as effective markers for predicting the
      onset of disease, they are not believed to be directly pathogenic to beta cells.
      Thus, activation of autoantibody-secreting B cells has long been regarded as a
      secondary consequence of the ongoing self-reactive T cell response. However,
      recently, studies in the nonobese diabetic mouse model of disease have
      demonstrated that B cells are an important component in the development of T1D by
      virtue of their ability to act as the preferential antigen presenting cell
      population required for efficient expansion of diabetogenic CD4+ T cells.
      Furthermore, autoantibodies might also be responsible for mediating early beta
      cell pathogenesis in this model.

PMID- 16580842
TI  - Three-layer matrix/sample preparation method for MALDI MS analysis of low
      nanomolar protein samples.
AB  - A robust and sensitive sample preparation method is presented for matrix-assisted
      laser desorption ionization (MALDI) mass spectrometric analysis of low nanomolar
      concentrations of proteins containing high amounts of common salts and buffers.
      This method involves the production of densely packed sub-micrometer matrix
      crystals by depositing a matrix solution on top of a matrix seed-layer prepared
      on a MALDI target. A sub-microliter aliquot of analyte solution is then directly
      added to the top of the matrix crystals to form a thin-layer. alpha-Cyano-4
      hydroxycinnamic acid (4-HCCA) is used as matrix and demonstrated to give better
      performance than other commonly used matrices, such as 2,5-dihydroxybenzoic acid
      (DHB), 2-(4-hydroxy-phenylazo) benzoic acid (HABA), or sinapinic acid. This three
      layer method is shown to be superior to the other MALDI sample preparation
      methods, particularly for handling low nanomolar protein solutions containing
      salts and buffers.

PMID- 16580841
TI  - Peptide conformation in gas phase probed by collision-induced dissociation and
      its correlation to conformation in condensed phases.
AB  - A kinetic peptide fragmentation model for quantitative prediction of peptide CID
      spectra in an ion trap mass spectrometer has been reported recently. When
      applying the model to predict the CID spectra of large peptides, it was often
      found that the predicted spectra differed significantly from their experimental
      spectra, presumably due to noncovalent interactions in these large polypeptides,
      which are not considered in the fragmentation model. As a result, site-specific
      quantitative information correlated to the secondary/tertiary structure of an
      ionized peptide may be extracted from its CID spectrum. To extract this
      information, the kinetic peptide fragmentation model was modified by
      incorporating conformation-related parameters. These parameters are optimized for
      best fit between the predicted and the experimental spectrum. A conformational
      stability map is then generated from these conformation-related parameters.
      Analysis of a few bioactive alpha-helical peptides including melittin, glucagon
      and neuropeptide Y by this technique demonstrated that their stability maps in
      the gas phase correlate strongly to their secondary structures in the condensed
      phases.

PMID- 16580844
TI  - Expression of the glycoprotein of viral haemorrhagic septicaemia virus (VHSV) on
      the surface of the fish cell line RTG-P1 induces type 1 interferon expression in
      neighbouring cells.
AB  - In the present study using a luciferase/Mx promoter reporter system, it was shown
      that the rainbow trout gonad cell line (RTG-P1), a fibroblastic cell line,
      produces IFN when transfected with a plasmid encoding the glycoprotein of VHSV
      but not with plasmid vector alone. Only a small percentage of the cells expressed
      the G protein on the surface membrane as indicated by immunostaining of
      transfected cells. When transfection was performed in the presence of monoclonal
      antibodies (Mab) to the glycoprotein, the production of interferon mRNA
      transcripts was reduced by over 50%. This indicates that the surface expression
      of G protein was the major mechanism of interferon induction and that most of the
      interferon was being expressed by cells neighbouring the transfected cells.

PMID- 16580843
TI  - Expression, purification, and circular dichroism analysis of human CDK9.
AB  - The human cyclin-dependent kinase 9 (CDK9) protein was expressed in E. coli BL21
      using the pET23a vector at 30 degrees C. Several milligrams of protein were
      purified from soluble fraction using ionic exchange and ATP-affinity
      chromatography. The structural quality of recombinant CDK9 and the estimation of
      its secondary structure were obtained by circular dichroism. Structural models of
      CDK9 presented 26% of helices in agreement with the spectra by circular dichroism
      analysis. This is the first report on human CDK9 expression in Escherichia coli
      and structure analysis and provides the first step for the development of CDK9
      inhibitors.

PMID- 16580845
TI  - Exploring the temporal dynamics of the spatial working memory n-back task using
      steady state visual evoked potentials (SSVEP).
AB  - The neural networks associated with spatial working memory (SWM) are well
      established. However, the temporal dynamics of SWM-related brain activity are
      less clear. This study examined changes in temporal neurophysiology during the
      spatial n-back task using steady state probe topography (SSPT) to record cortical
      steady state visual evoked potentials (SSVEPs) at 64 scalp locations. Twenty
      healthy male volunteers participated in the study. The findings identified three
      different time periods of significance during the spatial n-back task--an early
      perceptual/encoding period (approximately 0-500 ms), an early delay period just
      following the stimulus disappearing from view (approximately 850-1400 ms), and a
      late period lasting the final second of the delay and anticipation of the new
      stimulus (approximately 2500-3500 ms). The delay period was associated with
      increases in frontal and occipital region amplitude, consistent with previous
      findings in more basic working memory tasks. The two different SSVEP components
      during the delay appear reflective of the additional "executive" demands
      associated with the n-back and may suggest variable roles for the PFC during
      different stages of the delay. All three n-back levels demonstrated a relative
      consistent electrophysiological profile, indicating that this pattern is specific
      to the spatial n-back task. Nevertheless, these findings supported the hypothesis
      that memory load modulates activity within the networks identified, consistent
      with previous neuroimaging studies. The current findings may offer a framework in
      which to further investigate the temporal aspects of SWM.

PMID- 16580847
TI  - A new low temperature method for high yield isolation of chondrocytes from
      elderly human subjects and its applicability to mature articular cartilage from
      older animals.

PMID- 16580846
TI  - Temporal pattern of source activities evoked by different types of motion onset
      stimuli.
AB  - The aim of this study was to compare the time course of motion-related source
      activities evoked by the onset of different kinds of visual motion stimuli in
      human subjects. Event-related potentials (ERP) were recorded from 64 scalp
      electrodes in ten healthy subjects while they were viewing four different types
      of motion stimuli (translation, rotation, expansion and contraction). Following a
      new approach combining a current density reconstruction with clustering
      algorithms, source maxima in the time range from 50 to 400 ms after the onset of
      the visual stimulus were localized and the time courses of activation were
      elaborated. Six regions contributed significantly to source activity, half
      originating in the occipital lobe and half in the right parietal and right
      temporal cortex. The comparison of their time courses led to the following
      conclusions: (i) the different kinds of motion stimuli activated about the same
      areas of the brain but with different temporal patterns. (ii) Mainly parietal and
      extrastriate areas, but not V1/V2, were significantly involved in the
      differentiation of different kinds of motion. (iii) Contrasting the different
      kinds of motion onsets, responses from parietal areas were found mainly before
      those from lateral occipital areas. (iv) The classically defined N2 and P2
      components were significantly different among the four motion conditions, but not
      P1. The N2 motion-related component was elicited not only by lateral occipital
      areas and middle temporal areas but also by right parietal areas. (v) The
      rotation condition evoked a novel component P180, concomitant with an increased
      activity in the left middle temporal gyrus.

PMID- 16580848
TI  - A quantitative approach to measure joint pain in experimental osteoarthritis-
      evidence of a role for nitric oxide.
AB  - OBJECTIVES: To describe a method to study joint pain in experimental
      osteoarthritis (OA) and to study nitric oxide (NO) participation in experimental
      OA. DESIGN: Rats were subjected to anterior cruciate ligament transection (ACLT)
      (OA group) of the right knee and evaluated during 28 days. A sham group was false
      operated and a naive group received no manipulation. Joint pain was measured by
      recording the time the right hind paw fails to touch the surface while walking.
      Cell influx (CI) and nitrite levels were measured in joint exudates. Expression
      of inducible NO synthase (iNOS) in synovia was detected by immunostaining. For
      the specific purpose of pharmacological manipulation, groups received either
      indomethacin (2 mg/kg/day s.c. (subcutaneous)), meloxicam (6 mg/kg/day s.c.),
      morphine (200 microg intra-articularly), the non-selective NOS inhibitor L-N(G)
      nitroarginine methyl ester (L-NAME; 30 mg/kg/bid i.p. (intra-peritoneal)) or the
      selective iNOS inhibitor 1400W (0.5 mg/kg/day s.c.), given 30 min prior
      (prophylactic) or 4 days after (therapeutic) ACLT, until sacrifice, at 7 days.
      The respective non-treated groups received the vehicles. RESULTS: The OA group
      developed joint pain, as compared to sham and control groups (P<0.05).
      Significantly increased nitrite levels and iNOS immunostaining were seen in the
      OA group. Both indomethacin and meloxicam inhibited joint pain (P<0.05). Morphine
      inhibited joint pain, whereas this effect was blocked by co-administration of the
      mu-opioid receptor naloxone. CI was similar among all groups. Prophylactic but
      not therapeutic L-NAME or 1400W reduced joint pain. CONCLUSION: We describe a
      method to quantitate joint pain associated to weight bearing in the ACLT model.
      The joint pain is sensitive to classical antinociceptive compounds. NO release is
      associated to joint pain though NOS inhibition does not inhibit ongoing pain.

PMID- 16580849
TI  - Identification and cross-species comparison of canine osteoarthritic gene
      regulatory cis-elements.
AB  - OBJECTIVE: To better understand transcription regulation of osteoarthritis (OA)
      by examining common promoter motifs in canine osteoarthritic genes, to identify
      other genes containing these motifs and to assess the conservation of these
      motifs between canine, human, mouse and rat. DESIGN: Differentially expressed
      transcripts in canine OA were mapped to the human genome. We thus identified 20
      orthologous human transcripts representing 19 up-regulated genes and 62
      orthologous transcripts representing 60 down-regulated genes. The 5 kbp upstream
      regions of these transcripts were used to identify binding sites and build
      promoter models based on those sites. The human genome was subsequently searched
      for other transcripts likely to be regulated by the same promoter models.
      Orthologous transcripts were then identified in canine, rat and mouse for
      determination of potential cross-species conservation of binding sites comprising
      the promoter model. RESULTS: Four promoter models containing 5-6 transcripts and
      5-8 common transcription factor binding sites were developed. They include
      binding sites for AP-4, AP-2alpha and gamma, and E2F. Several hundred other human
      genes were found to contain these promoter motifs. Furthermore these motifs were
      significantly over represented in the orthologous genes in canine, rat and mouse
      genomes. CONCLUSIONS: We have developed and applied a computational methodology
      to identify common promoter elements implicated in OA and shared amongst four
      higher vertebrates. The transcription factors associated with these binding sites
      and other genes driven by these promoter motifs have been implicated in OA,
      chondrocyte development and with other biological factors involved in the
      disease.

PMID- 16580850
TI  - Comparison of ultrasonography, radiography and a single computed tomography slice
      for fluid identification within the feline tympanic bulla.
AB  - Evaluation of the tympanic bulla (TB) in cases of acute feline otitis media can
      be a diagnostic challenge, although a feature often associated with this
      condition is the accumulation of fluid or material within the middle ear cavity.
      A technique is reported allowing optimum imaging of the feline TB using
      ultrasound (US) and recording of the appearance of gas and fluid-filled TB. A
      random number of bullae in 42 feline cadavers were filled with lubricant and
      rostroventral-caudodorsal oblique radiographs, single slice computed tomography
      (CT) images and US images were created and interpreted by blinded operators. The
      content (fluid or gas) of each TB was determined using each technique and the
      cadavers were then frozen and sectioned for confirmation. CT remained the most
      accurate diagnostic method, but US produced better results than radiology. Given
      the advantages of US over other imaging techniques, these results suggest that
      further work is warranted to determine applications of this modality in the
      evaluation of clinical cases of feline otitis media.

PMID- 16580851
TI  - The efficacy of non-pharmacological interventions in the management of procedural
      pain in preterm and term neonates. A systematic literature review.
AB  - BACKGROUND: Neonates in a neonatal intensive care unit are exposed to a high
      number of painful procedures. Since repeated and sustained pain can have
      consequences for the neurological and behaviour-oriented development of the
      newborn, the greatest attention needs to be paid to systematic pain management in
      neonatology. Non-pharmacological treatment methods are being increasingly
      discussed with regard to pain prevention and relief either alone or in
      combination with pharmacological treatment. AIMS: To identify effective non
      pharmacological interventions with regard to procedural pain in neonates.
      METHODS: A literature search was conducted via the MedLine, CINAHL, Cochrane
      Library databases and complemented by a handsearch. The literature search covered
      the period from 1984 to 2004. Data were extracted according to pre-defined
      criteria by two independent reviewers and methodological quality was assessed.
      RESULTS: 13 randomised controlled studies and two meta-analyses were taken into
      consideration with regard to the question of current nursing practice of non
      pharmacological pain management methods. The selected interventions were "non
      nutritive sucking", "music", "swaddling", "positioning", "olfactory and
      multisensorial stimulation", "kangaroo care" and "maternal touch". There is
      evidence that the methods of "non-nutritive sucking", "swaddling" and
      "facilitated tucking" do have a pain-alleviating effect on neonates. CONCLUSIONS:
      Some of the non-pharmacological interventions have an evident favourable effect
      on pulse rate, respiration and oxygen saturation, on the reduction of motor
      activity, and on the excitation states after invasive measures. However,
      unambiguous evidence of this still remains to be presented. Further research
      should emphasise the use of validated pain assessment instruments for the
      evaluation of the pain-alleviating effect of non-pharmacological interventions.

PMID- 16580852
TI  - A large volume flat coil probe for oriented membrane proteins.
AB  - 15N detection of mechanically aligned membrane proteins benefits from large
      sample volumes that compensate for the low sensitivity of the observe nuclei,
      dilute sample preparation, and for the poor filling factor arising from the
      presence of alignment plates. Use of larger multi-tuned solenoids, however, is
      limited by wavelength effects that lead to inhomogeneous RF fields across the
      sample, complicating cross-polarization experiments. We describe a 600 MHz 15N-1H
      solid-state NMR probe with large (580 mm3) RF solenoid for high-power, multi
      pulse sequence experiments, such as polarization inversion spin exchange at the
      magic angle (PISEMA). In order to provide efficient detection for 15N, a 4-turn
      solenoidal sample coil is used that exceeds 0.27 lambda at the 600 MHz 1H
      resonance. A balanced tuning-matching circuit is employed to preserve RF
      homogeneity across the sample for adequate magnetization transfer from 1H to 15N.
      We describe a procedure for optimization of the shorted 1/4 lambda coaxial trap
      that allows for the sufficiently strong RF fields in both 1H and 15N channels to
      be achieved within the power limits of 300 W 1H and 1 kW 15N amplifiers. The 8 x
      6 x 12 mm solenoid sustains simultaneous B1 irradiation of 100 kHz at 1H
      frequency and 51 kHz at 15N frequency for at least 5 ms with 265 and 700 W of
      input power in the respective channels. The probe functionality is demonstrated
      by 2D 15N-1H PISEMA spectroscopy for two applications at 600 MHz.

PMID- 16580854
TI  - Oxidative stress and its effects during dehydration.
AB  - Water is usually thought to be required for the living state, but several
      organisms are capable of surviving complete dehydration (anhydrobiotes).
      Elucidation of the mechanisms of tolerance against dehydration may lead to
      development of new methods for preserving biological materials that do not
      normally support drying, which is of enormous practical importance in industry,
      in clinical medicine as well as in agriculture. One of the molecular mechanisms
      of damage leading to death in desiccation-sensitive cells upon drying is free
      radical attack to phospholipids, DNA and proteins. This review aims to summarize
      the strategies used by anhydrobiotes to cope with the danger of oxygen toxicity
      and to present our recent results about the importance of some antioxidant
      defense systems in the dehydration tolerance of Saccharomyces cerevisiae, a usual
      model in the study of stress response.

PMID- 16580853
TI  - QCRNA 1.0: a database of quantum calculations for RNA catalysis.
AB  - This work outlines a new on-line database of quantum calculations for RNA
      catalysis (QCRNA) available via the worldwide web at
      http://theory.chem.umn.edu/QCRNA. The database contains high-level density
      functional calculations for a large range of molecules, complexes and chemical
      mechanisms important to phosphoryl transfer reactions and RNA catalysis.
      Calculations are performed using a strict, consistent protocol such that a wealth
      of cross-comparisons can be made to elucidate meaningful trends in biological
      phosphate reactivity. Currently, around 2000 molecules have been collected in
      varying charge states in the gas phase and in solution. Solvation was treated
      with both the PCM and COSMO continuum solvation models. The data can be used to
      study important trends in reactivity of biological phosphates, or used as
      benchmark data for the design of new semiempirical quantum models for hybrid
      quantum mechanical/molecular mechanical simulations.

PMID- 16580855
TI  - Anabolic effects of feeding beta2-adrenergic agonists on rainbow trout muscle
      proteases and proteins.
AB  - beta2-Adrenergic agonists (BAAs) act as repartitioning agents in domestic animals
      by redistributing nutrients away from adipose tissue and towards muscle
      accretion. The mechanism involves altering the rates of protein degradation and
      synthesis. The aim of this study was to test the effects of chronic feeding of
      the BAAs clenbuterol (CLEN) and ractopamine (RACT) on rainbow trout (RBT) muscle.
      Specifically, we examined the activities and mRNA levels of genes in the major
      proteolytic pathways including calpains, the multi-catalytic proteasome and
      cathepsins, and the mRNA levels of genes encoding the myofibrillar proteins, fast
      twitch and slow-twitch myosin heavy chains (f-MHC and s-MHC, respectively), and
      the cytoskeletal protein, beta-actin. RACT feeding significantly increased mRNA
      transcripts of the calpain catalytic subunit (Capn1), the regulatory subunit
      (cpns), and the calpastatin large isoform (CAST-L), without affecting the calpain
      enzyme activity. CLEN feeding significantly increased mRNA levels of the
      proteasome alpha subunit without a corresponding change in 20S enzyme activity.
      RACT significantly decreased cathepsin D activity without affecting mRNA levels
      suggesting that the action of RACT may be at the post-transcriptional level. In
      addition, both CLEN and RACT significantly increased mRNA transcripts of f-MHC
      and beta-actin genes suggesting an anabolic role of BAAs on myofibrillar and
      cytoskeletal proteins. Neither CLEN nor RACT altered mRNA expression of the s-MHC
      gene indicating no transformation of muscle fiber-types. This study supports a
      role for BAAs in inducing RBT muscle accretion by altering both protein synthesis
      and degradation.

PMID- 16580857
TI  - Melatonin effects on food intake and activity rhythms in two fish species with
      different activity patterns: Diurnal (goldfish) and nocturnal (tench).
AB  - Melatonin has several known physiological functions, the main one being
      synchronization of daily and seasonal rhythms. In addition, melatonin has been
      reported to influence food intake and behavioral rhythms with varying results
      depending on the species. The aim of this research was to evaluate the effects of
      intraperitoneal melatonin injection on food intake and locomotor activity in two
      different fish species: goldfish (diurnal) and tench (nocturnal), under different
      light regimes: constant light (LL) conditions or LD 12:12, with melatonin
      administration at mid-light (ML), mid-dark (MD), and after a 1-h light pulse at
      MD. In addition to these acute tests, in the case of goldfish we also
      investigated the effects of daily melatonin administration for 1 week. Our
      results indicated that acute melatonin administration significantly decreased
      goldfish food intake (16-52% inhibition, depending on the light regime) and
      locomotor activity (55-100%), with the chronic treatment inducing a similar total
      food intake inhibition that persisted for 7 days. In tench, a nocturnal fish
      species, acute melatonin administration at MD and ML reduced food intake (37% and
      29%, respectively), while locomotor activity was not affected at MD and slightly
      increased at ML. Taken together, these results indicated that melatonin reduced
      food intake in both species, while its effects on locomotor activity depended on
      the time of administration (light or dark phase) and the activity patterns of the
      species.

PMID- 16580856
TI  - In vitro effect of vitellogenin on steroid production by ovarian follicles of
      greenback flounder Rhombosolea tapirina.
AB  - Ovarian follicles from vitellogenic greenback flounder (Rhombosolea tapirina)
      were incubated in L15 medium alone, or containing human chorionic gonadotropin
      (hCG), dibutyryl cyclic AMP (dbcAMP) or the steroid precursors testosterone (T),
      17-hydroxyprogesterone (17P) and androstenedione (A) in the presence of
      vitellogenin (Vtg) at 0.1-5.0mg mL(-)(1). Medium concentrations of 17beta
      estradiol (E(2)) and T were measured by radioimmunoassay. HCG generally
      stimulated follicular E(2) but not T production, whereas 17P, A and T stimulated
      production of E(2), T, and E(2) respectively. Treatment of follicles with dbcAMP
      inhibited follicular E(2) production, but increased follicular T production at
      high doses. The effect of low concentrations of Vtg on follicular steroid
      production was variable; however, higher doses of Vtg significantly suppressed
      basal, hCG-, dbcAMP- and steroid precursor-stimulated follicular E(2) and T
      production. The results of this study show that high concentrations of Vtg may
      suppress follicular steroid production by interfering in the steroidogenic
      pathway. This suggests that Vtg may regulate its own production by limiting the
      ovarian production of E(2).

PMID- 16580858
TI  - Responses of whole body protein synthesis, nitrogen retention and glucose
      kinetics to supplemental starch in goats.
AB  - An isotope dilution experiment was conducted to determine the effect of
      metabolizable energy intake (MEI) as starch on whole body protein synthesis
      (WBPS), nitrogen (N) retention and glucose irreversible loss rate (ILR) in four
      adult goats (Capra hircus). The goats were fed isonitrogenous diets containing
      three different metabolizable energy (1.0, 1.5 and 2.0 times maintenance) twice
      daily. Energy above maintenance was supplemented with cornstarch. The WBPS and
      glucose ILR during 5 to 7 h after feeding were measured by a primed-continuous
      infusion of [2H5]phenylalanine, [2H2]tyrosine, [2H4]tyrosine and [13C6]glucose
      for 4 h, with measurements of plasma concentrations of metabolites and insulin.
      Ruminal characteristics were also determined. Increasing MEI improved N
      retention, despite decreased digestible N. Increasing MEI decreased ruminal pH
      and ammonia nitrogen. In plasma, decreased urea N, increased total amino N and
      tyrosine, and trends for increases in phenylalanine and insulin resulted from
      increasing MEI. Increasing MEI increased ILR of glucose, phenylalanine and
      tyrosine, and hydroxylation rate of phenylalanine and WBPS. We conclude that in
      goats increasing MEI as starch enhances WBPS in the absorptive state and N
      retention, despite a decrease in digestible N. These changes are probably
      associated with both decreased ammonia absorption and increased amino acid
      absorption.

PMID- 16580859
TI  - Subcellular localization of muscle FBPase in carp (Cyprinus carpio) tissues.
AB  - Subcellular localization of muscle FBPase-a regulatory enzyme of glyconeogenesis
      was investigated in carp using immunohistochemistry and protein exchange method.
      Results of the experiments revealed that, in striated muscles, FBPase associates
      with alpha-actinin of the Z-line and co-localizes with aldolase. Additionally, in
      cardiac and smooth muscle cells FBPase is present inside the nuclei. In the light
      of findings on mammalian muscle FBPase, the data presented here indicates that
      interaction of the enzyme with specific cellular partners and nuclear presence of
      FBPase is a general phenomenon in contemporary vertebrates.

PMID- 16580860
TI  - Uncontrolled acromegaly is associated with progressive mitral valvular
      regurgitation.
AB  - INTRODUCTION: Recent cross-sectional studies have documented an association
      between acromegaly and regurgitant valvular heart disease. The aim of this study
      was to evaluate the change in prevalence of valvular heart disease in relation to
      the clinical activity, because the natural history of valvular changes in
      acromegaly is unknown. PATIENTS AND METHODS: Valvular regurgitation was assessed
      in 37 acromegalic patients (18 patients with active disease, and 19 with
      controlled disease) by conventional two-dimensional and Doppler echocardiography
      before and after an interval of 1.9 years (range 1.5-3.0 years). RESULTS: At
      baseline, valvular regurgitation (mitral and aortic sites combined) was present
      in 46% of the patients and increased to 67% at follow-up (P=0.008). Mitral
      regurgitation increased significantly from 32% to 60% (P=0.002), but no change
      was noted for the aortic valve (27% vs. 31%, NS). In patients with active
      disease, valvular regurgitation increased significantly from 56% at baseline to
      88% at follow-up (P=0.031) due to a significant increase of mitral regurgitation
      from 39% to 78% at follow-up (P=0.016). In contrast, no increase in valvular
      regurgitation was found in patients with controlled disease. CONCLUSION: The
      prevalence of mitral, but not aortic, valvular regurgitation increased in
      patients with active acromegaly during follow-up. Patients with acromegaly
      require adequate cardiac evaluation and follow-up to establish the extent and
      progression of valvular involvement.

PMID- 16580861
TI  - High cerebral guanidinoacetate and variable creatine concentrations in
      argininosuccinate synthetase and lyase deficiency: implications for treatment?
AB  - Cerebral creatine and guanidinoacetate and blood and urine metabolites were
      studied in four patients with argininosuccinate synthetase (ASS) or
      argininosuccinate lyase (ASL) deficiency receiving large doses of arginine. Urine
      and blood metabolites varied largely. Cerebral guanidinoacetate was increased in
      all patients, while cerebral creatine was low in ASS and high in ASL deficiency.
      Because high cerebral guanidinoacetate might be toxic, lowering the arginine
      supplementation with additional creatine supplementation might be important.

PMID- 16580862
TI  - Ammonium transport properties of HEK293 cells expressing RhCG mutants:
      preliminary analysis of structure/function by site-directed mutagenesis.
AB  - We have recently shown by monitoring intracellular pHi with a stopped-flow
      fluorimeter, that when expressed in HEK293 kidney cells, two Rh glycoproteins,
      RhBG and RhCG, facilitated NH3 movement across the plasma membrane. Based on the
      results of 3D structure determination of AmtB, a bacterial member of the
      Amt/Mep/Rh superfamily, and of homology modeling of the human Rh proteins, we
      have attempted to determine if some selected residues predicted to be located in
      the pore or in the vestibule of the channel are essential for NH3 transport.
      Accordingly, wild type and mutant forms of RhCG were expressed in HEK293 cells
      and their ammonium function was analyzed with the stopped-flow fluorimeter. Some
      mutants that were not expressed at a significant level in HEK293 could not be
      tested for function, but mutations at positions F74, V137 and F235 (equivalent
      positions in AmtB: I28, L114, F215, respectively) resulted in a severe reduction
      of NH3 transport.

PMID- 16580863
TI  - Monoclonal anti-D antibodies to prevent alloimmunization: lessons from clinical
      trials.
AB  - In the past 20 years, numerous monoclonal anti-D antibodies have been developed
      in order to replace the human plasma derived anti-D immunoglobulins, using
      different in vitro functional assays as screening methods. Some of these
      monoclonal antibodies have been evaluated in exploratory in vivo clinical trials,
      notably for their ability to mediate the clearance of D-positive red cells. A
      review of these reported trials is presented and the results are analyzed in the
      light of the newly published hypothesis conferring an important role to some Fc
      FcgammaR interactions and to the glycosylation-dependent potency of the
      monoclonal anti-D antibodies.

PMID- 16580864
TI  - Electrogenic ammonium transport by renal Rhbg.
AB  - The recently cloned, non-erythrocyte Rh glycoproteins (Rhbg and Rhcg) are
      expressed in the intercalated cells of the renal collecting duct. The apical Rhcg
      and the basolateral Rhbg are likely involved in NH3 and/or NH4+ transport, yet
      the characteristics of this transport are not yet certain. In this study we
      investigated the mechanism of NH4+ transport by Rhbg and Rhcg expressed in
      Xenopus oocytes. We used a two-electrode voltage-clamp and ion-selective
      microelectrodes to measure NH4+-induced currents (I(NH4)) and changes in pHi,
      respectively. In oocytes expressing Rhcg, exposure to bath [NH4+] of 2.5-20 mM
      induced inward currents that were slightly more than those in H2O-injected
      (control) oocytes. I-V plots in the presence of NH4+ showed a small increase in
      slope conductance only at positive potentials. On the other hand, in oocytes
      expressing Rhbg, 5 mM NH4+ induced an inward I(NH4) of -79 nA, decreased pHi
      (DeltapHi) by 0.13 at a rate (dpHi/dt) of -2 7 x 10(-4) pH/s and depolarized the
      cell by 45 mV. These changes were significantly more than those in control
      oocytes. I-V plots in the presence of NH4+ showed substantial increase in
      conductance. Amiloride (1 mM) inhibited I(NH4), DeltapHi and dpHi/dt in oocytes
      expressing Rhbg but not in control oocytes. Raising bath [NH4+] in increments
      from 1 to 20 mM elicited a faster dpHi/dt, a larger decrease in pHi and a larger
      depolarization. Net NH4+ flux by Rhbg (estimated from dpHi/dt) was proportional
      to [NH4+] gradient and followed saturation kinetics with an apparent Km of 2.3
      mM. Methyl ammonium (5 mM) induced a current of -63 nA in Rhbg oocytes but did
      not cause any change in control oocytes. These data indicate that: 1) Rhbg
      transport of NH4+ is electrogenic. 2) Methyl ammonium is transported by Rhbg. 3)
      NH4+ transport by Rhbg is saturated at high concentrations with Michaelis-Menten
      kinetics.

PMID- 16580866
TI  - [Risk factors for prosthesis exposure in treatment of genital prolapse via the
      vaginal approach].

PMID- 16580865
TI  - Functional interaction between Rh proteins and the spectrin-based skeleton in
      erythroid and epithelial cells.
AB  - We summarize the different experimental approaches which provide evidence that
      direct interaction of Rh and RhAG to ankyrin-R constitutes, together with the AE
      1 (Band 3)-ankyrin-protein 4.2 and GPC-protein 4.1-p55 complexes, another major
      anchoring site between the red cell membrane bilayer and the underlying spectrin
      based skeleton. The observations that some residues of the ankyrin binding site
      are mutated in Rh and RhAG proteins from some weak D and Rh(null) variants,
      respectively, suggest that the Rh-RhAG/ankyrin-R interaction plays a crucial role
      in the biosynthesis and/or the stability of the Rh complex in the red cell
      membrane. Similarly, binding to ankyrin G is required for cell surface expression
      of the non-erythroid member of the Rh protein family, RhBG, at the basolateral
      membrane domain of polarized epithelial cells. The next challenge will be to
      determine whether binding to the membrane skeleton may be critical for the
      emerging ammonium transport function of Rh proteins in erythroid and non
      erythroid cells.

PMID- 16580867
TI  - [Management of endometriosis of the urinary tract].
AB  - Endometriosis of the urinary tract (bladder and/or ureter) is rare and concerns 1
      2% of cases of endometriosis. Surgical management is usually mandatory. Rate of
      peri operative morbidity is low. There is a risk of functional (dysuria, chronic
      hypogastric pains, imperiosity) and anatomical recurrences (0-15 and 0-10%
      respectively). Surgical treatment of bladder and/or ureteral endometriosis
      requires informed consent of patients and multidisciplinary management.

PMID- 16580869
TI  - Haemorrhagic complication of acute necrotizing pancreatitis presenting with
      sudden death.
AB  - Certain complications of acute pancreatitis may lead to death, and of these,
      haemorrhage caused by rupture of a peri-pancreatic vessel is among the most
      dangerous. The case reported here was remarkable because the onset of acute
      necrotizing pancreatitis was completely asymptomatic and the severe haemorrhage
      of the portal vein that caused the patient's death was only discovered at
      autopsy. The onset of abdominal pain was immediately followed by death.

PMID- 16580870
TI  - Generalist genes: implications for the cognitive sciences.
AB  - In the 'generalist genes' hypothesis, it is suggested that the same genes affect
      most cognitive abilities and disabilities. This recently proposed hypothesis is
      based on considerable multivariate genetic research showing that there is
      substantial genetic overlap between such broad areas of cognition as language,
      reading, mathematics and general cognitive ability. We assume that the hypothesis
      is correct and consider here its implications for cognitive neuroscience. In our
      opinion, the two key genetic concepts of pleiotropy (in which one gene affects
      many traits) and polygenicity (in which many genes affect a trait) that underlie
      the generalist genes hypothesis imply a 'generalist brain'. That is, the genetic
      input into brain structure and function is general not specific.

PMID- 16580871
TI  - Unraveling the complex network of cuticular structure and function.
AB  - A hydrophobic cuticle is deposited at the outermost extracellular matrix of the
      epidermis in primary tissues of terrestrial plants. Besides forming a protective
      shield against the environment, the cuticle is potentially involved in several
      developmental processes during plant growth. A high degree of variation in
      cuticle composition and structure exists between different plant species and
      tissues. Lots of progress has been made recently in understanding the different
      steps of biosynthesis, transport, and deposition of cuticular components.
      However, the molecular mechanisms that underlie cuticular function remain largely
      elusive.

PMID- 16580872
TI  - CF mediated G1 arrest is associated with induction of p27(Kip1) and inhibition of
      cyclin D1 expression in human hepatoma HepG2 cells.
AB  - CF is a kind of diterpenoid which was first isolated and purified from Chinese
      tropical plants by our laboratory. Our previous works have demonstrated it could
      inhibit the proliferation of several malignant tumor cell lines and stimulate
      them to differentiate to normal cells. In this article we investigated the effect
      of CF on human hepatocellulor carcinoma HepG2 cell viability, differentiation,
      cell cycle distribution and G1 cell cycle related genes expression. We also
      detected the effect of retinoic acid (RA) which was used as positive control and
      the effect of combination CF+RA. Our data suggested that CF could be useful to
      induce growth arrest and differentiation in HepG2 cell lines, and could reverse
      the transformed phenotype. This anti-tumor effect was due to G1 arrest in cell
      cycle which was associated with an increase of p27(Kip1) and a decrease of cyclin
      D1 expression, so CF might be a useful targeted therapy strategy for HCC. Results
      also showed RA has a different mechanism from CF on G1 arrest, and CF has not
      synergistic anti-tumor effect with RA on HepG2 treatment.

PMID- 16580873
TI  - Coordinated intracellular translocation of phosphoinositide-specific
      phospholipase C-delta with the cell cycle.
AB  - The delta family phosphoinositide (PI)-specific phospholipase C (PLC) are most
      fundamental forms of eukaryotic PI-PLCs. Despite the presence of lipid targeting
      domains such as the PH domain and C2 domain, the isoforms are also found in the
      cytoplasm and nucleus as well as at the plasma membrane. The isoforms have
      sequences or regions that can serve as a nuclear localization signal (NLS) and a
      nuclear export signal (NES). Their intracellular localization differs from one
      isoform to another, presumably due to the difference in the transport equilibrium
      balanced by the strength of the two signals of each isoform. Even for a
      particular isoform, its intracellular localization seems to vary during the cell
      cycle. As an example, PLCdelta(1), which is generally found at the plasma
      membrane and in the cytoplasm of quiescent cells, localizes to discrete nuclear
      structures in the G(1)/S boundary of the cell cycle. This may be at least partly
      due to an increase in intracellular Ca(2+), since Ca(2+) facilitates the
      formation of a nuclear transport complex comprised of PLCdelta(1) and importin
      beta1, a carrier molecule for the nuclear import. PLCdelta(1) as well as
      PLCdelta(4) may play a pivotal role in controlling the initiation of DNA
      synthesis in S phase. Spatio-temporal changes in the levels of PtdIns(4,5)P(2)
      seem to be another major determinant for the localization and regulation of the
      delta isoforms. High nuclear PtdIns(4,5)P(2) levels are associated with the
      G(1)/S phases. After entering M phase, PtdIns(4,5)P(2) synthesis at sites of cell
      division occurs and PLCs seem to localize to the cleavage furrow during
      cytokinesis. Coordinated translocation of PLCs with the cell cycle or with stress
      responses may result in changes in intra-nuclear environments and local membrane
      architectures that modulate proliferation and differentiation. In this review,
      recent findings regarding the molecular machineries and mechanisms of the
      nucleocytoplasmic shuttling as well as roles in the cell cycle progression of the
      delta isoforms of PLC will be discussed.

PMID- 16580874
TI  - Structured triglycerides containing caprylic (8:0) and oleic (18:1) fatty acids
      reduce blood cholesterol concentrations and aortic cholesterol accumulation in
      hamsters.
AB  - The effects of structured triglycerides containing one long chain fatty acid
      (oleic acid, C18:1) and one short chain saturated fatty acid (caprylic acid, 8:0)
      on lipidemia, liver and aortic cholesterol, and fecal neutral sterol excretion
      were investigated in male Golden Syrian hamsters fed a hypercholesterolemic
      regimen consisting of 89.9% commercial ration to which was added 10% coconut oil
      and 0.1% cholesterol (w/w). After 2 weeks on the HCD diet, the hamsters were
      bled, following an overnight fast (16 h) and placed into one of three dietary
      treatments of eight animals each based on similar plasma cholesterol levels. The
      hamsters either continued on the HCD diet or were placed on diets in which the
      coconut oil was replaced by one of two structured triglycerides, namely, 1(3),2
      dicaproyl-3(1)-oleoylglycerol (OCC) or 1,3-dicaproyl-2-oleoylglycerol (COC) at
      10% by weight. Plasma total cholesterol (TC) in hamsters fed the OCC and COC
      compared to the HCD were reduced 40% and 49%, respectively (P<0.05). Similarly,
      hamsters fed the OCC and COC diets reduced their plasma nonHDL cholesterol levels
      by 47% and 57%, respectively (P<0.05), compared to hamsters fed the HCD after 2
      weeks of dietary treatment. Although hamsters fed the OCC (-26%) and COC (-32%)
      had significantly lower plasma HDL levels compared to HCD, (P<0.05), the plasma
      nonHDL/HDL cholesterol ratio was significantly lower (P<0.05) compared to the HCD
      for the OCC-fed (-27%) and the COC-fed (-38%) hamsters, respectively. Compared to
      the HCD group, aortic esterified cholesterol was 20% and 53% lower for the OCC
      and COC groups, respectively, with the latter reaching statistical significance,
      P<0.05. In conclusion, the hamsters fed the structured triglyceride oils had
      lower blood cholesterol levels and lower aortic accumulation of cholesterol
      compared to the control fed hamsters.

PMID- 16580875
TI  - Contribution of lipid mediators to the regulation of phosphatidylcholine
      synthesis by angiotensin.
AB  - Angiotensin stimulates a cellular mitogenic response via the AT1 receptor. We
      have examined the effect of angiotensin on the rate of phosphatidylcholine (PC)
      synthesis and have begun to dissect the pathway linking the AT1 receptor to the
      rate-limiting enzyme in PC synthesis, CTP: phosphocholine cytidylyltransferase
      (CCT), using CHO cells engineered to express the AT1a receptor. Since CCT can be
      directly activated by lipid mediators, we probed for their involvement in the PC
      synthesis response to angiotensin. Angiotensin stimulated CCT activity and PC
      synthesis two- to threefold after a 30-min delay. The kinetics of this
      stimulation most closely paralleled an increase in diacylglycerol (DAG) derived
      from myristic acid-enriched phospholipids. The production of arachidonic acid,
      phosphatidic acid, or reactive oxygen species either peaked much earlier or not
      at all. Moreover, manipulation of the intracellular supply of oxygen free
      radicals, arachidonic acid, HETEs, or phosphatidic acid (using inhibitors and/or
      exogenous addition) did not generate parallel effects on the rate of PC
      synthesis. Restricting the production of DAG by inhibition of PLCbeta with U73122
      reduced both basal and angiotensin-stimulated PC synthesis. The U73122 inhibition
      of PC synthesis was accompanied by a similar inhibition of ERK1/2
      phosphorylation. Addition of exogenous DAG stimulated basal and angiotensin
      dependent PC synthesis, and partially reversed the effect of the PLC inhibitor on
      PC synthesis. These results do not provide support for lipid mediators as direct
      stimulators of CCT and PC synthesis downstream of angiotensin, but give rise to
      the idea that angiotensin effects might be mediated via ERK1/2.

PMID- 16580877
TI  - Encouraging cycling through a pilot cycling proficiency training program among
      adults in central Sydney.
AB  - In the face of declining population levels of physical activity, programs that
      encourage cycling represent an under-developed strategy in Australia. In 2003, we
      implemented a pilot cycling proficiency training (CPT) program for adults in
      central Sydney, New South Wales. To evaluate the program, participants completed
      pre- and post-course self-administered questionnaires and participated in a
      follow-up telephone interview 2 months after their course. Between April and
      December 2003, 20 CPT courses were conducted. Of 113 people who started a course,
      81 (72%) completed at least one course (beginner or intermediate) and 105 (93%)
      took part in the pre and follow-up interview. Participant satisfaction with all
      aspects of the course was high. At 2-month follow-up, the course had
      significantly increased participants' self-reported skills and confidence for
      cycling. More than half of the participants (56%) said they cycled more 2 months
      after the course. There was a 40% increase in participants having cycled in the
      previous week at follow-up among baseline non-cyclists, although this was not
      statistically significant. There was also a significant increase in weekly
      participation in other forms of moderate intensity physical activity. Overall,
      the program was reasonably successful, particularly among those people not
      cycling at baseline. Cycling proficiency training for adults is one strategy that
      can supplement other active transport policies to encourage physical activity,
      although bicycle friendly urban planning and policies are still required to
      create more supportive environments for cyclists.

PMID- 16580876
TI  - Printed circuit board industry.
AB  - The printed circuit board is the platform upon which microelectronic components
      such as semiconductor chips and capacitors are mounted. It provides the
      electrical interconnections between components and is found in virtually all
      electronics products. Once considered low technology, the printed circuit board
      is evolving into a high-technology product. Printed circuit board manufacturing
      is highly complicated, requiring large equipment investments and over 50 process
      steps. Many of the high-speed, miniaturized printed circuit boards are now
      manufactured in cleanrooms with the same health and safety problems posed by
      other microelectronics manufacturing. Asia produces three-fourths of the world's
      printed circuit boards. In Asian countries, glycol ethers are the major solvents
      used in the printed circuit board industry. Large quantities of hazardous
      chemicals such as formaldehyde, dimethylformamide, and lead are used by the
      printed circuit board industry. For decades, chemically intensive and often
      sloppy manufacturing processes exposed tens of thousands of workers to a large
      number of chemicals that are now known to be reproductive toxicants and
      carcinogens. The printed circuit board industry has exposed workers to high doses
      of toxic metals, solvents, acids, and photolithographic chemicals. Only recently
      has there been any serious effort to diminish the quantity of lead distributed
      worldwide by the printed circuit board industry. Billions of electronics products
      have been discarded in every region of the world. This paper summarizes recent
      regulatory and enforcement efforts.

PMID- 16580878
TI  - Positional differences in fitness and anthropometric characteristics in
      Australian football.
AB  - To evaluate the utility of fitness assessment and trends in drafting of players
      in the Australian Football League, we analysed height, mass, skinfolds, 20-m
      sprint, vertical jump, agility run and endurance assessed in the 495 players
      attending the annual national draft camps between 1999 and 2004. Effects of
      player position and assessment year were expressed as standardised mean
      differences (Cohen effect sizes) and interpreted qualitatively. Effect of birth
      month on chance of being drafted, which may be important in team sports, was also
      analysed. Compared with midfield players, ruckmen, tall forwards and tall
      defenders were decisively taller (effect-size range 1.33-1.95, large) and heavier
      (1.30-1.63, large), but had poorer sprint speed (0.23-0.57, small), aerobic
      ability (0.66-1.18, moderate) and agility (0.64-1.11, moderate). The only
      substantial changes in fitness scores over the 5-year period were an increase in
      height (0.76, moderate) and an increase in 20-m sprint time (0.39, small). A
      majority (65%) of players attending the camps were born in the first half of a
      given year, but their chance of being drafted (70%) was similar to that of
      players born in the second half (64%). We conclude that fitness assessment is
      useful for differentiating between player positions and identifying some annual
      trends in recruitment in Australian football, and that players with a second half
      birth month have been disadvantaged with lower representation at the national
      draft camp.

PMID- 16580879
TI  - Left ventricular non-compaction associated with a genetic variant of the CYP2C9
      gene.
AB  - Polymorphisms in the CYP2C9 gene can have a significant impact on drug therapy by
      affecting the pharmacokinetics of frequently prescribed drugs, such as
      phenprocoumon and warfarin. It is essential therefore that genetic CYP2C9
      variants are excluded in patients with a suspected intolerance of anticoagulant
      therapy. Here we present the first report of a case of left ventricular non
      compaction syndrome associated with a genetic variant of the CYP2C9 gene in a 45
      year-old woman with myocardial insufficiency who was scheduled for implantation
      of a cardioverter defibrillator.

PMID- 16580880
TI  - Chloroquine and primaquine: combining old drugs as a new weapon against
      falciparum malaria?
AB  - A recent publication has shown that primaquine, a drug used to clear liver-stage
      Plasmodium vivax infection, acts as a chloroquine-resistance reversing agent for
      Plasmodium falciparum in culture. Primaquine is active as a chloroquine
      resistance reverser at concentrations that could be clinically relevant. As
      primaquine and chloroquine are already used together in the treatment of P.
      vivax, this is potentially a cheap way of reviving and extending the life of
      chloroquine.

PMID- 16580881
TI  - AAV serotype 8-mediated gene delivery of a soluble VEGF receptor to the CNS for
      the treatment of glioblastoma.
AB  - The presence of the blood-brain barrier complicates drug delivery in the
      development of therapeutic agents for the treatment of glioblastoma multiforme
      (GBM). The use of local gene transfer in the brain has the potential to overcome
      this delivery barrier by allowing the expression of therapeutic agents directly
      at the tumor site. In this study, we describe the development of a recombinant
      adeno-associated (rAAV) serotype 8 vector that encodes an optimized soluble
      inhibitor, termed sVEGFR1/R2, of vascular endothelial growth factor (VEGF). VEGF
      is an angiogenic factor highly up-regulated in GBM tumor tissue and correlates
      with disease progression. In subcutaneous models of GBM, VEGF inhibition
      following rAAV-mediated gene transfer significantly reduces overall tumor volume
      and increases median survival time following a single administration of vector.
      Using orthotopic brain tumor models of GBM, we find that direct intracranial
      administration of the rAAV-sVEGFR1/R2 vector to the tumor site demonstrates anti
      tumor efficacy at doses that are not efficacious following systemic delivery of
      the vector. We propose that rAAV-mediated gene transfer of a potent soluble VEGF
      inhibitor in the CNS represents an effective antiangiogenic treatment strategy
      for GBM.

PMID- 16580882
TI  - Stimulating full-length SMN2 expression by delivering bifunctional RNAs via a
      viral vector.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder
      that is the leading genetic cause of infant mortality. SMA is caused by the loss
      of survival motor neuron-1 (SMN1). In humans, a nearly identical copy gene is
      present, called SMN2. SMN2 is retained in all SMA patients and encodes an
      identical protein compared to SMN1. However, a single silent nucleotide
      difference in SMN2 exon 7 results in the production of a spliced isoform (called
      SMNDelta7) that encodes a nonfunctional protein. The presence of SMN2 represents
      a unique therapeutic target since SMN2 has the capacity to encode a fully
      functional protein. Here we describe an in vivo delivery system for short
      bifunctional RNAs that modulate SMN2 splicing. Bifunctional RNAs derive their
      name from the presence of two domains: an antisense RNA sequence specific to a
      target RNA and an untethered RNA segment that serves as a binding platform for
      splicing factors. Plasmid-based and recombinant adeno-associated virus vectors
      were developed that expressed bifunctional RNAs that stimulated SMN2 exon 7
      inclusion and full-length SMN protein in patient fibroblasts. These experiments
      provide a mechanism to modulate splicing from a variety of genetic contexts and
      demonstrate directly a novel therapeutic approach for SMA.

PMID- 16580883
TI  - Adenovirus type 5 interactions with human blood cells may compromise systemic
      delivery.
AB  - Intravenous delivery of adenovirus vectors requires that the virus is not
      inactivated in the bloodstream. Serum neutralizing activity is well documented,
      but we show here that type 5 adenovirus also interacts with human blood cells.
      Over 90% of a typical virus dose binds to human (but not murine) erythrocytes ex
      vivo, and samples from a patient administered adenovirus in a clinical trial
      showed that over 98% of viral DNA in the blood was cell associated. In contrast,
      nearly all viral genomes in the murine bloodstream are free in the plasma.
      Adenovirus bound to human blood cells fails to infect A549 lung carcinoma cells,
      although dilution to below 1.7 x 10(7) blood cells/ml relieves this inhibition.
      Addition of blood cells can prevent infection by adenovirus that has been
      prebound to A549 cells. Adenovirus also associates with human neutrophils and
      monocytes ex vivo, particularly in the presence of autologous plasma, giving dose
      dependent transgene expression in CD14-positive monocytes. Finally, although
      plasma with a high neutralizing titer (defined on A549 cells) inhibits monocyte
      infection, weakly neutralizing plasma can actually enhance monocyte transduction.
      This may increase antigen presentation following intravenous injection, while
      blood cell binding may both decrease access of the virus to extravascular targets
      and inhibit infection of cells to which the virus does gain access.

PMID- 16580884
TI  - Cognitive performance of patients with mesial temporal lobe epilepsy is not
      associated with human prion protein gene variant allele at codons 129 and 171.
AB  - Cognitive impairment has long been recognized in people with medically refractory
      epilepsies. Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE
      HS), the most common surgically remediable epileptic syndrome, has been
      associated with a cellular prion protein (PrPc) gene (Prnp) variant allele at
      codon 171. The polymorphism consisting of a methionine-for-valine substitution at
      codon 129 has been associated with early cognitive deterioration in elderly
      people and patients with Down syndrome. The same variant allele in homozygosis
      (V129V) has been associated to a lower long-term memory in healthy humans. PrPc
      mediates several processes related to neuroplasticity, and its role in cognitive
      processes remains unknown. In this study, we evaluated the genetic contribution
      of Prnp alleles to cognitive performance in patients with MTLE-HS. Cognitive
      performance, measured with 19 neuropsychological tests, of patients with
      refractory MTLE-HS with the normal Prnp genotypes was compared with that of
      patients with the variant alleles at codons 129 and 171. With the effects of
      clinical, demographic, electrophysiological, and neuroimaging variable
      interactions controlled by multiple linear regression analysis and adjustment for
      multiple test comparisons, the presence of Prnp variant alleles was found not to
      be significantly associated to cognitive performance of patients with MTLE-HS.
      The presence of variant alleles at codons 129 and 171 is not associated to
      cognitive performance of patients with refractory MTLE-HS.

PMID- 16580885
TI  - Does cadmium pollution affect reproduction in the clam Ruditapes decussatus? A
      one-year case study.
AB  - The effect of cadmium (Cd) on the reproduction of Ruditapes decussatus was
      monitored over a period of 12 months, from June 2001 to June 2002. Two sites
      "Bordj d'Ungha" and "El Hofra" differing by their degree of cadmium contamination
      were chosen in the Gulf of Gabes area (Tunisia). Annual mean concentrations of Cd
      in the whole soft tissues of clams from the site El Hofra were more than 4 times
      higher than those from the site Bordj d'Ungha (reference site). The gametogenic
      cycle of the clam R. decussatus was also investigated by histological examination
      and monthly observations of gonadal sections in a population of clams from both
      sites. The results show that gametogenesis occurred from March to December in
      clams from both sites. Nevertheless, spawning and emission of gametes were
      synchronized in both sexes from only the clams of the reference site. Although
      this species is considered as gonochoristic, 6.6% of hermaphroditic cases were
      observed in clams from both sites in which gametes of both males and females were
      in ripe stage. Moreover, the period of ripening of sexual products led to an
      increase of condition index and to a decrease of Cd concentrations in the whole
      soft tissues of clams from both sites, hence reflecting the phenomenon of
      "biological dilution".

PMID- 16580887
TI  - PP2A is required for centromeric localization of Sgo1 and proper chromosome
      segregation.
AB  - Loss of sister-chromatid cohesion triggers chromosome segregation in mitosis and
      occurs through two mechanisms in vertebrate cells: (1) phosphorylation and
      removal of cohesin from chromosome arms by mitotic kinases, including Plk1,
      during prophase, and (2) cleavage of centromeric cohesin by separase at the
      metaphase-anaphase transition. Bub1 and the MEI-S332/Shugoshin (Sgo1) family of
      proteins protect centromeric cohesin from mitotic kinases during prophase. We
      show that human Sgo1 binds to protein phosphatase 2A (PP2A). PP2A localizes to
      centromeres in a Bub1-dependent manner. The Sgo1-PP2A interaction is required for
      centromeric localization of Sgo1 and proper chromosome segregation in human
      cells. Depletion of Plk1 by RNA interference (RNAi) restores centromeric
      localization of Sgo1 and prevents chromosome missegregation in cells depleted of
      PP2A_Aalpha. Our findings suggest that Bub1 targets PP2A to centromeres, which in
      turn maintains Sgo1 at centromeres by counteracting Plk1-mediated chromosome
      removal of Sgo1.

PMID- 16580888
TI  - Detection of angiotensin II mediated nitric oxide release within the nucleus of
      the solitary tract using electron-paramagnetic resonance (EPR) spectroscopy.
AB  - We previously identified an action of nitric oxide (NO) within the nucleus
      tractus solitarii (NTS) that attenuates the cardiac component of the baroreceptor
      reflex. In the present study we have tested the hypothesis that angiotensin II
      (AngII), acting on angiotensin type 1 receptors (AT1R), can release NO within the
      NTS and that its actions are mediated by soluble guanylate cyclase (sGC).
      Utilising cryogenic electron paramagnetic resonance (EPR), we have detected NO
      release in brainstem samples following AngII, but not saline, microinjections
      into the NTS. In these experiments, we confirmed that both AngII and a NO donor
      (diethylamine NONOate) in the NTS both depressed the baroreflex bradycardia. In
      additional studies, we showed that the latter effects were both sensitive to
      blockade of sGC using 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ). To
      initiate studies to resolve the cellular source of NO released by angiotensin II
      in the NTS, we performed immunohistochemical/electron microscopy studies on the
      distribution of AT1R. We found AT1R located on NTS neurones and blood vessels.
      Since a rise in intracellular calcium [Ca]i levels is prerequisite for nNOS
      activation, we imaged responses in [Ca]i in NTS neurones during exposure to AngII
      in vitro using confocal microscopy. Our data indicate a paucity of neurones
      showing changes in [Ca]i when exposed to AngII (200 nM). We suggest that AngII
      induced release of NO is from non-neuronal sites. With the presence of AT1R on
      blood vessel endothelial cells we propose that AngII released NO in the NTS is
      due to activation of endothelial nitric oxide synthase located within the
      endothelium. The present study supports the novel concept that AngII can trigger
      NO release in the NTS by a mechanism of vascular-neuronal signalling that affects
      central neuronal networks regulating cardiovascular function.

PMID- 16580889
TI  - Somatic pain sensitivity during formation and healing of acetic acid-induced
      gastric ulcers in conscious rats.
AB  - A classical feature of visceral pain is its referring to somatic locations.
      Gastric ulcer is a source of visceral pain. In the present study we investigated
      whether gastric ulcers may trigger the changes in somatic nociception. For this
      aim somatic pain sensitivity was estimated under conditions of gastric ulcer
      development and healing. Gastric ulcers were induced by luminal application of
      60% acetic acid under surgical conditions. Control rats were subjected to the
      same surgical procedure, but with the application of saline instead of the acid.
      Somatic pain sensitivity (tail flick latency), plasma corticosterone level,
      adrenal and thymus weight were investigated under conditions of the formation and
      the healing of gastric ulcers. The application of the acid resulted in the
      formation of kissing gastric ulcers, the increase of somatic pain sensitivity
      (the decrease of tail flick latency) as well as the appearance of typical signs
      of chronic stress: long-lasting increase of plasma corticosterone level, adrenal
      gland hypertrophy and thymus gland involution. Natural healing of gastric ulcers
      was accompanied by restoration of pain sensitivity as well as attenuation of the
      signs of chronic stress. Delay of ulcer healing by the daily indomethacin
      administration (2 mg/kg, s.c.) prevented the restoration of somatic pain
      sensitivity. The results suggest that chronic gastric ulcers may trigger somatic
      hypersensitivity.

PMID- 16580890
TI  - Stress-induced cardiac stimulation and fever: common hypothalamic origins and
      brainstem mechanisms.
AB  - Our past results provide considerable evidence that activation of neurons
      somewhere in the region of the dorsomedial hypothalamus (DMH) plays a key role in
      the generation of many of the effects typically seen in "emotional" stress in
      rats, including activation of the hypothalamic-pituitary-adrenal (HPA) axis, the
      neuroendocrine hallmark of the generalized response to stress, and
      sympathetically mediated tachycardia. More recently, we demonstrated that (1) the
      tachycardia resulting either from chemical stimulation of the DMH or from
      experimental stress is markedly attenuated by microinjection of the GABAA
      receptor agonist muscimol, a neuronal inhibitor, into the medullary raphe
      pallidus (RP); and (2) the specific subregion of the DMH mediating stimulation
      induced tachycardia corresponds to the dorsal hypothalamic area (DHA), a site
      where neurons projecting to the RP are densely concentrated. Thus, the pathway
      from neurons in the DHA to sympathetic premotor neurons in the RP may constitute
      a key relay mediating the increases in heart rate seen in emotional stress--a
      role that had never been proposed previously for either of these regions.
      Instead, sympathetic premotor neurons were known to exist in the RP but had been
      most closely associated with sympathetic thermoregulatory mechanisms, including
      activation of brown fat, the principal means for nonshivering thermogenesis in
      rats, and cutaneous vasoconstriction in the tail, an important method of
      conserving body heat in this species. These sympathetic effects serve to maintain
      body temperature in a cold environment or to increase it in fever--and are
      typically accompanied by tachycardia. Interestingly, we and others have now shown
      that (1) disinhibition of neurons in the DMH also increases body temperature, at
      least in part through activation of brown fat, (2) microinjection of the neuronal
      inhibitor muscimol into the DMH reduces experimental fever and the associated
      tachycardia in rats. We hypothesize that activation of neurons in the DMH
      mediates both the increased body temperature and cardiac stimulation produced in
      rats by experimental "emotional" stress and fever, and that these effects are
      mediated in large part through direct projections to sympathetic premotor neurons
      in the RP. Thus, this pathway may constitute a common effector circuit upon which
      a variety of forebrain inputs converge in response to diverse environmental
      challenges.

PMID- 16580891
TI  - A novel method for glucose determination based on electrochemical impedance
      spectroscopy using glucose oxidase self-assembled biosensor.
AB  - A method is developed for quantitative determination of glucose using
      electrochemical impedance spectroscopy (EIS). The method is based on immobilized
      glucose oxidase (GOx) on the topside of gold mercaptopropionic acid self
      assembled monolayers (Au-MPA-GOx SAMs) electrode and mediation of electron
      transfer by parabenzoquinone (PBQ). The PBQ is reduced to hydroquinone (H(2)Q),
      which in turn is oxidized at Au electrode in diffusion layer. An increase in the
      glucose concentration results in an increase in the diffusion current density of
      the H(2)Q oxidation, which corresponds to a decrease in the faradaic charge
      transfer resistance (R(ct)) obtained from the EIS measurements. Glucose is
      quantified from linear variation of the sensor response (1/R(ct)) as a function
      of glucose concentration in solution. The method is straightforward and
      nondestructive. The dynamic range for determination of glucose is extended to
      more than two orders of magnitude. A detection limit of 15.6 microM with a
      sensitivity of 9.66 x 10(-7) Omega(-1)mM(-1) is obtained.

PMID- 16580892
TI  - Voltammetry and in situ scanning tunnelling microscopy of de novo designed heme
      protein monolayers on Au(111)-electrode surfaces.
AB  - In the present work, we report the electrochemical characterization and in situ
      scanning tunnelling microscopy (STM) studies of monolayers of an artificial de
      novo designed heme protein MOP-C, covalently immobilized on modified Au(111)
      surfaces. The protein forms closely packed monolayers, which remain electroactive
      upon immobilization. In situ STM images show circular structures indicating that
      MOP-C stands upright on the surface in accordance with the molecular design.
      Despite the large spatial extension of MOP-C, about 5 nm in height, conditions
      could be found where tip/sample interaction is minimal and proteins could be
      imaged without detectable tip interference. The results indicate further that the
      structural sensitivity of (in situ) STM depends to a significant extent on
      associated electron transfer kinetics. In the present case, the heme group does
      not contribute significantly to the tunnelling current, apparently due to slow
      electron transfer kinetics. As a consequence, STM images of heme-containing and
      heme-free MOP-C did not reveal any notable differences in apparent height or
      physical extension. The apparent height of heme-containing MOP-C did not show any
      dependence on the substrate potential being varied around the redox potential of
      the protein. The mere presence of an accessible molecular energy level is not
      sufficient to result in detectable tunnelling current modulation.

PMID- 16580893
TI  - Entrainment of breathing in cyclists and non-cyclists during arm and leg
      exercise.
AB  - The purpose of this study was to compare the incidence of entrainment of
      breathing (ENT) between cyclists (C; n=8) and non-cyclists (NC; n=8) during leg
      cycling (LC) and arm cycling (AC). No subjects were training regularly in upper
      body endurance exercise. Day 1 consisted of spirometry and a VO2max test on both
      an arm and leg ergometer in random order separated by at least 60 min. On Day 2,
      subjects performed both AC and LC exercise with each session consisting of 5 min
      of warm-up at 20% and three consecutive 6 min loads at 40%, 60%, and 80% of task
      specific peak power output (WL1, WL2, WL3, respectively). Sessions were separated
      by at least 45 min. The final 3 min of each load were analyzed for entrainment of
      pedal and breathing frequencies using integer and half-integer ratios. A total of
      six subjects were unable to complete at least one exercise session at WL3 and
      therefore this load was excluded from analysis. Mean % VO2max during exercise was
      not different between cyclists and controls with respect to intensity and mode
      (AC= approximately 50% and 70%; LC= approximately 55% and 75% at WL1 and WL2,
      respectively). A repeated measures ANOVA revealed no effect on incidence of
      entrainment (%ENT) by group, mode of exercise, or exercise intensity (p=0.12,
      0.24, and 0.88, respectively). %ENT was highest in cyclists during leg exercise
      (cyclists: LC=32%; AC=19%; controls: LC=18%; AC=21%) however this difference was
      not significant (p=0.07). In all situations that would be considered unfamiliar
      for both groups %ENT was similar. These results suggest that during cycling
      exercise at intensities of 75% VO2max or less, regular training may result in
      higher %ENT and that ENT is not transferable to an unfamiliar mode of exercise
      using different muscle groups.

PMID- 16580894
TI  - Pharmacokinetic study of orphenadrine using high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS).
AB  - We developed and validated a simple, rapid, and accurate HPLC-MS/MS method with
      simple protein precipitation for the determination of orphenadrine. Injection-to
      injection running time was 3 min with a retention time of orphenadrine of 1.1
      min. The linear assay range was 1-200 ng/mL (r2 > 0.99). The intra- and inter
      assay imprecisions were CV 0.6-4.2% and CV 1.6-6.1%, respectively. The accuracy,
      extraction recovery, specificity and stability were satisfactory. Using the
      measured plasma concentrations of orphenadrine in 24 healthy subjects,
      pharmacokinetic profiles of orphenadrine were evaluated (AUC(0-72,) 1565+/-731 ng
      h/mL, Cmax 82.8+/-26.2 ng/mL, Tmax 3.0+/-0.9 h, elimination half-life 25.8+/-10.3
      h).

PMID- 16580895
TI  - Enzymatic and biochemical properties of a novel human serine dehydratase isoform.
AB  - A cDNA clone similar to human serine dehydratase (SDH) is deposited in the
      GenBank/EMBL databases, but its structural and functional bases remain unknown.
      Despite the occurrence of mRNA, the expected protein level was found to be low in
      cultured cells. To learn about physicochemical properties of the protein, we
      expressed the cDNA in Escherichia coli, and compared the expressed protein with
      that of a hepatic SDH. The purified protein showed l-serine and l-threonine
      dehydratase activity, demonstrating to be an isoform of SDH. However, their Km
      and Vmax constants were different in a range of two-order. Removal of Pro128 from
      the hepatic SDH consisting of 328 residues, which is missing in the corresponding
      position of the isoform consisting of 329 residues, significantly changed the
      Michaelis constants and Kd value for pyridoxal 5'-phosphate, whereas addition of
      a proline residue to the isoform was without effect. These findings suggest the
      difference in the structures of the active sites of the two enzymes. Another
      striking feature was that the expressed level of the isoform in E. coli was 7
      fold lower than that of the hepatic SDH. Substitution of Val for Leu287 in the
      isoform dramatically increased the protein level. The high yield of the mutated
      isoform was also confirmed by the in vitro transcription and translation
      experiment. The poor expression of the isoform could be explained by the more
      stable secondary structure of the mRNA than that of the hepatic SDH mRNA. The
      present findings may provide a clue as to why the protein level in cultured cells
      is low.

PMID- 16580896
TI  - Tumor necrosis factor-alpha: alternative role as an inhibitor of osteoclast
      formation in vitro.
AB  - TNFalpha is known to stimulate the development and activity of osteoclasts and of
      bone resorption. The cytokine was found to mediate bone loss in conjunction with
      inflammatory diseases such as rheumatoid arthritis or chronic aseptic
      inflammation induced by wear particles from implants and was suggested to be a
      prerequisite for the loss of bone mass under estrogen deficiency. In the present
      study, the regulation of osteoclastogenesis by TNFalpha was investigated in co
      cultures of osteoblasts and bone marrow or spleen cells and in cultures of bone
      marrow and spleen cells grown with CSF-1 and RANKL. Low concentrations of
      TNFalpha (1 ng/ml) caused a >90% decrease in the number of osteoclasts in co
      cultures, but did not affect the development of osteoclasts from bone marrow
      cells. In cultures with p55TNFR(-/-) osteoblasts and wt BMC, the inhibitory
      effect was abrogated and TNFalpha induced an increase in the number of
      osteoclasts in a dose-dependent manner. Osteoblasts were found to release the
      inhibitory factor(s) into the culture supernatant after simultaneous treatment
      with 1,25(OH)(2)D(3) and TNFalpha, this activity, but not its release, being
      resistant to treatment with anti-TNFalpha antibodies. Dexamethasone blocked the
      secretion of the TNFalpha-dependent inhibitor by osteoblasts, while stimulating
      the development of osteoclasts. The data suggest that the effects of TNFalpha on
      the differentiation of osteoclast lineage cells and on bone metabolism may be
      more complex than hitherto assumed and that these effects may play a role in vivo
      during therapies for inflammatory diseases.

PMID- 16580897
TI  - The beneficial effect of intravenous zoledronic acid therapy following an acute
      stroke in rats.
AB  - PURPOSE: Changes of bone metabolism begin from the initial stages of stroke;
      therefore, early prevention of these changes has become important. The most
      appropriate target for preventive therapy is to restrict the profound increase in
      osteoclastic bone resorption that occur soon after stroke. Oral bisphosphonates,
      which selectively target osteoclasts and their precursors, are appropriate drugs,
      but dysphagia or drowsiness after acute stroke can make it difficult to easily
      administer these compounds to stroke patients. The intravenous (IV)
      administration of bisphosphonates is an alternative method that can overcome
      these limitations. In order to determine the effect of IV bisphosphonates at the
      initial stages of stroke for preventing bone loss, an experiment using ischemic
      stroke rats was conducted. METHODS: Female Sprague-Dawley rats (n = 100) were
      randomly divided into four separate groups; sham surgery and vehicle-treated
      group (sham-vehicle), stroke and vehicle-treated group (stroke-vehicle), stroke
      with low-dose zoledronic acid treatment group (stroke-low) and stroke with high
      dose zoledronic acid treatment group (stroke-high). Permanent occlusion of the
      left middle cerebral artery was performed, resulting in right hemiplegia. The
      bone mineral density (BMD) of the 4th and 5th lumbar vertebrae and the femur on
      the stroke side were measured in vivo on the day before stroke and on the 10th
      and 21st day after stroke. The osteocalcin and carboxy-terminal telopeptide blood
      levels were measured on the 10th and 21st day after stroke. The BMD of the
      excised proximal tibia and the maximum load of femoral neck were measured on the
      21st day after stroke. RESULTS: After 21 days of stroke, the BMD of the lumbar
      vertebrae, femur, and excised tibia and the maximum load of the femoral neck in
      the sham-vehicle, stroke-low, and stroke-high groups were significantly higher
      than those in the stroke-vehicle group (P < 0.05). The carboxy-terminal
      telopeptide levels in the sham-vehicle and stroke-high groups were significantly
      lower than those in the stroke-vehicle group (P < 0.05). CONCLUSION: The results
      suggest that IV zoledronic acid treatment might prevent bone loss during the
      initial stages of stroke.

PMID- 16580899
TI  - Rofecoxib regulates the expression of genes related to the matrix
      metalloproteinase pathway in humans: implication for the adverse effects of
      cyclooxygenase-2 inhibitors.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandins contribute
      to acute inflammation and pain, as well as resolution of inflammation; inhibition
      of COX-2 results in persistence of inflammation. Because matrix
      metalloproteinases (MMPs) play an essential role in inflammatory tissue injury
      and their activity is regulated by COX-2-derived prostaglandin E2, we evaluated
      whether COX-2 inhibition is associated with MMP overexpression during acute
      inflammation. METHODS: A total of 102 oral mucosal biopsy specimens were taken
      from 51 healthy volunteers who required extraction of impacted third molars.
      Subjects randomly received either rofecoxib (50 mg daily), ibuprofen (400 mg 4
      times per day), or placebo 90 minutes before surgery and up to 48 hours after
      surgery. Total ribonucleic acid extracted from each biopsy specimen was used to
      analyze changes in gene expression related to the MMP pathway after tissue injury
      and drug treatments by use of microarray and quantitative real-time polymerase
      chain reaction in this clinical model of acute inflammation. RESULTS: Following
      tissue injury, rofecoxib increased the expression of genes associated with
      degradation of the extracellular matrix, including MMP-1 (64.7 +/- 6.5, P =
      .010), MMP-3 (41.7 +/- 4.8, P = .007), PLAT (encoding tissue plasminogen
      activator) (10.9 +/- 4.6, P = .032), and IL8 (encoding interleukin 8) (8.3 +/-
      6.7, P = .020), and decreased the expression of TIMP3 (encoding tissue inhibitor
      of metalloproteinase 3) (6.2 +/- 2.8, P = .027). Ibuprofen produced similar
      effects on the expression of MMP-1 (23.4 +/- 5.0, P = .016) and MMP-3 (26.3 +/-
      4.2, P = .003). In contrast, the expression of these genes was not statistically
      changed after tissue injury in the placebo group. The microarray data were in
      concordance with the changes in gene expression confirmed by quantitative real
      time polymerase chain reaction. CONCLUSION: These findings provide evidence at
      the transcriptional level that inhibition of COX-2, in the presence of acute
      inflammation, induces changes in gene expression related to the MMP pathway.
      These changes may contribute to the adverse effects attributed to COX-2
      inhibition by interfering with resolution of inflammation.

PMID- 16580898
TI  - Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1,
      and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements.
AB  - INTRODUCTION: The primary objective of this study was to determine whether
      variability in warfarin dose requirements is determined by common polymorphisms
      in genes whose products are involved in the pharmacodynamics and pharmacokinetics
      of warfarin, namely, the coagulation factors, vitamin K epoxide reductase complex
      subunit 1 (VKORC1), and cytochrome P450 (CYP) 2C9. METHODS: Patients (N = 350)
      receiving stable doses of warfarin at 3 consecutive visits were enrolled, and a
      deoxyribonucleic acid sample was collected. Samples were genotyped for
      polymorphisms in the factor II, factor VII, factor X, VKORC1, and CYP2C9 genes. A
      stepwise linear regression analysis was used to determine the independent effects
      of genetic and nongenetic factors on mean warfarin dose requirements. RESULTS:
      Variables associated with lower warfarin dose requirements were VKORC1 3673 AA
      genotype (P < .0001), VKORC1 3673 GA genotype (P < .0001), 1 variant CYP2C9
      allele (P < .0001), 2 variant CYP2C9 alleles (P = .0004), increasing age (P =
      .0005), concomitant CYP2C9 inhibitors (P = .0005), and goal international
      normalized ratio (P = .01). Variables associated with higher warfarin dose
      requirements were weight (P < .0001), current smoker status (P = .0009), mean
      international normalized ratio (P = .001), concomitant CYP2C9 inducers (P =
      .006), factor X insertion/deletion genotype (P = .01), factor X
      insertion/insertion genotype (P = .04), factor VII deletion/deletion genotype (P
      = .04), and calculated vitamin K intake (P = .05). The linear regression model
      explained 51.4% of the variability in warfarin dose requirements. CONCLUSION:
      Polymorphisms in warfarin drug target and metabolizing enzyme genes, in addition
      to nongenetic factors, were important determinants of warfarin dose requirements.

PMID- 16580900
TI  - Environmental and genetic factors associated with morphine response in the
      postoperative period.
AB  - OBJECTIVE: The aim of this study was to investigate the respective influence of
      genetic and nongenetic factors on morphine dose requirements and adverse effects
      after colorectal surgery. METHODS: Seventy-four patients who planned to undergo
      colorectal surgery were included in this pilot study. The cumulative 24-hour
      postoperative dose of morphine and postoperative nausea or vomiting requiring the
      antiemetic ondansetron were the 2 clinical end points. The association of patient
      characteristics, A118G mu-opioid receptor (OPRM1) single-nucleotide polymorphism
      (SNP); T802C uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) SNP; and 2
      adenosine triphosphate-binding cassette, subfamily B, member 1 (ABCB1) (multidrug
      resistance 1 [MDR1]) exonic SNPs (G2677T/A and C3435T) with study end points was
      investigated. RESULTS: Age, creatinine clearance, and the regular use of
      psychotropic agents were found to be significantly associated with postoperative
      morphine dose requirements by univariate analysis. Multivariate analysis
      identified that age (P = .01) and the use of psychotropic agents before surgery
      (P = .03) were positively associated with a higher rate of morphine consumption.
      A higher weight (P = .05) and the ABCB1 homozygous GG-CC diplotype (P = .03) were
      significantly associated with fewer morphine side effects by univariate analysis.
      The homozygous ABCB1 diplotype (GG-CC) conferred an odds ratio of 0.12 (95%
      confidence interval, 0.01-0.98) with regard to the use of ondansetron for
      postoperative nausea or vomiting. Multivariate analysis identified that the ABCB1
      GG-CC diplotype was the only borderline-significant (P = .07) predictive factor
      of morphine side effects. CONCLUSION: Age and prior use of psychotropic agents
      are associated with postoperative morphine dose requirements. Whether ABCB1
      polymorphisms might predict morphine side effects remains to be determined.

PMID- 16580901
TI  - MDR1 genotype is associated with hepatic cytochrome P450 3A4 basal and induction
      phenotype.
AB  - OBJECTIVES: Variant cytochrome P450 (CYP) 3A4 alleles cannot explain human
      variation in CYP3A4 expression. This study investigated whether common single
      nucleotide polymorphisms (SNPs) in multidrug resistance 1 (MDR1), encoding P
      glycoprotein, or the pregnane X receptor (PXR) were associated with basal or
      inducible CYP3A4 expression. METHODS: MDR1 G2677T and C3435T SNPs and a PXR 6
      base pair (bp) deletion were genotyped in the deoxyribonucleic acid from 144
      human livers in 3 cohorts each phenotyped for basal or rifampin (INN, rifampicin)
      inducible hepatic CYP3A4 expression (or both) and in 57 human small bowel biopsy
      specimens from 3 cohorts each phenotyped for either basal or rifampin-induced
      CYP3A4 expression (or both). RESULTS: Hepatic CYP3A4 expression/function was
      significantly higher in persons homozygous for the MDR1 2677T (Ser893) allele
      compared with persons homozygous for 2677G (Ala893) in all 3 hepatic cohorts. For
      example, homozygous MDR1 2677 TT livers had higher midazolam hydroxylase activity
      than homozygous 2677 GG livers (1831 +/- 1336 pmol x min(-1) x mg protein(-1)
      versus 1060 +/- 552 pmol x min(-1) x mg protein(-1), P = .03). In 2 of the 3
      groups the association was observed in men but not in women. For example,
      homozygous MDR1 2677 TT male hepatocytes had significantly higher testosterone
      6beta-hydroxylase activity compared with homozygous 2677 GG livers (0.120 +/-
      0.06 pmol x min(-1) x mg protein(-1) versus 0.069 +/- 0.04 pmol x min(-1) x mg
      protein(-1), P = .0002). Conversely, rifampin induction of testosterone 6beta
      hydroxylation in primary human hepatocytes was significantly higher in persons
      homozygous for 2677G (12.0 +/- 5.7-fold) compared with MDR1 homozygous TT
      carriers (7.3 +/- 4.6-fold) (P = .01). Suggestive evidence for higher CYP3A4
      expression in MDR1 2677T carriers was also observed in human intestines. CYP3A4
      expression was also related to a 6-bp deletion in PXR in 2 of the liver cohorts.
      Two-factor ANOVA analysis revealed a significant interaction between the MDR1
      2677 SNP and the PXR 6-bp deletion influencing CYP3A4 expression (P = .007).
      CONCLUSIONS: Individuals homozygous for the MDR1 2677T allele show enhanced
      constitutive CYP3A4 expression in the liver and intestine, as compared with those
      homozygous for the MDR1 2677G allele, particularly in men. Conversely, the
      magnitude of CYP3A4 induction by rifampin is greater in persons with the MDR1
      2677G allele and is inversely related to baseline CYP3A4 expression. MDR1 likely
      influences basal CYP3A4 expression by limiting the intracellular concentration of
      an endogenous regulator. MDR1 genotype may be a useful predictor of basal CYP3A4
      and the extent of some CYP3A4-mediated drug interactions in humans. Moreover, the
      influence of MDR1 genotype on CYP3A4 expression adds additional complexity to
      determining the relative contribution of the MDR1 alleles to the disposition of
      substrates shared by CYP3A4 and MDR1/P-glycoprotein.

PMID- 16580903
TI  - Comparison of midazolam and simvastatin as cytochrome P450 3A probes.
AB  - OBJECTIVE: Our objective was to compare simvastatin with the validated probe
      midazolam in the assessment of cytochrome P450 (CYP) 3A activity. METHODS: This
      study used an open-label, fixed-sequential, 3-way crossover study design.
      Nineteen subjects received oral doses of 0.075 mg/kg midazolam and 40 mg
      simvastatin during 3 phases (baseline, after inhibition with 400 mg ketoconazole
      for 10 days, and after induction with 600 mg rifampin [INN, rifampicin] for 9
      days). Serial plasma concentrations of midazolam and simvastatin were obtained.
      Oral clearances of midazolam and simvastatin were compared. RESULTS: Oral
      midazolam clearance decreased after pretreatment with ketoconazole (from a
      geometric mean of 25 mL x min(-1) x kg(-1) [range, 12-57 mL x min(-1) x kg(-1)]
      to 2.7 mL x min(-1) x kg(-1) [range, 1.2-8.5 mL x min(-1) x kg(-1)], P < .001)
      and increased after pretreatment with rifampin (to a geometric mean of 203 mL x
      min(-1) x kg(-1) [range, 125-371 mL x min(-1) x kg(-1)], P < .001). Oral
      simvastatin clearance decreased after ketoconazole (from a geometric mean of 312
      mL x min(-1) x kg(-1) [range, 151-1478 mL x min(-1) x kg(-1)] to 25 mL x min(-1)
      x kg(-1) [range, 8.0-147 mL x min(-1) x kg(-1)], P < .001) and increased after
      rifampin (to a geometric mean of 3536 mL x min(-1) x kg(-1) [range, 413-10,329 mL
      x min(-1) x kg(-1)], P < .001). The change in simvastatin clearance was highly
      variable from baseline to inhibition (6- to 33-fold decrease) and from baseline
      to induction (2- to 39-fold increase) compared with midazolam (7- to 18-fold
      decrease during inhibition and 4- to 12-fold increase during induction).
      Midazolam and simvastatin oral clearances were correlated for all study phases (r
      = 0.5 and P = .03 for baseline and r = 0.53 and P = .02 for inhibition) but were
      weakest for induction (r = -0.031, P = .22). The area under the concentration
      time curve inhibitory ratio for midazolam was 9.4 versus 12.4 for simvastatin (r
      = 0.3, P = .03). CONCLUSIONS: Compared with midazolam, simvastatin is a
      nonvalidated, suboptimal probe for studying CYP3A drug interactions because of
      its lack of CYP3A specificity.

PMID- 16580902
TI  - Identification and characterization of CYP3A4*20, a novel rare CYP3A4 allele
      without functional activity.
AB  - BACKGROUND: The major drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 is
      genetically conserved. One outlier of Brazilian descent was found in a clinical
      pharmacokinetic trial exhibiting a 6-fold higher exposure than expected to an
      investigational drug, shown to be a CYP3A4 substrate. We aimed to investigate the
      genetic background of this finding. METHODS: The allelic variant of the CYP3A4
      gene present in the outlier was sequenced, and the corresponding complementary
      deoxyribonucleic acid was expressed in yeast and human embryonic kidney cells.
      The outlier was phenotyped by use of intravenous administration of 1 mg
      midazolam. Analysis of phenotype and genotype correlation was carried out. The
      prevalence of the new allele was screened for in a white population. RESULTS: We
      identified a subject who heterozygously carried a novel CYP3A4 allele, named
      CYP3A4*20, with a premature stop codon yielding a truncated protein. Heterologous
      expression revealed that the CYP3A4.20 enzyme does not incorporate heme and thus
      is devoid of catalytic activity. CYP3A phenotyping in vivo showed that CYP3A4*20
      exhibits a clear genotype-phenotype correlation, demonstrated by the subject's
      low systemic midazolam clearance (2.99 mL x min(-1) x kg(-1)). Genotyping of a
      white German population (n = 428) and relatives of the subject, as well as a
      review of published CYP3A4 sequencing data, suggests that CYP3A4*20 is a rare
      variant allele (<0.06% in white subjects). CONCLUSIONS: CYP3A4*20 represents the
      first CYP3A4 allele to be identified that has been shown to be devoid of
      functional activity. It causes an intermediate CYP3A4 metabolizer phenotype in a
      heterozygous carrier. Subjects of this genotype might be susceptible to side
      effects during drug therapy with substrates or inhibitors of CYP3A4.

PMID- 16580904
TI  - Effect of voriconazole on the pharmacokinetics and pharmacodynamics of
      intravenous and oral midazolam.
AB  - OBJECTIVE: Our objective was to assess the effect of the antimycotic voriconazole
      on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam.
      METHODS: We used a randomized, crossover study design. Ten healthy male
      volunteers were given either no pretreatment (control phase) or voriconazole
      (voriconazole phase) orally, 400 mg twice daily on the first day and 200 mg twice
      daily on the second day. Midazolam was given, either 0.05 mg/kg intravenously or
      7.5 mg orally, 1 hour after the last dose of voriconazole and during the control
      phase. Plasma concentrations of midazolam, alpha-hydroxymidazolam, and
      voriconazole were determined for 24 hours and pharmacodynamic variables measured
      for 12 hours. RESULTS: Voriconazole reduced the clearance of intravenous
      midazolam by 72% (P < .001) and increased its elimination half-life from 2.8 to
      8.3 hours (P < .001). Voriconazole increased the peak concentration and the area
      under the plasma concentration-time curve of oral midazolam by 3.8- and 10.3
      fold, respectively (P < .001). The bioavailability of oral midazolam was
      increased from 31% to 84% (P < .001). Voriconazole profoundly increased the
      psychomotor effects of oral midazolam (P < .001) but only weakly increased the
      effects of intravenous midazolam. CONCLUSION: When midazolam is given as small
      intravenous bolus doses, its effect is not increased to a clinically significant
      degree by voriconazole. The use of large midazolam doses increases the risk of
      clinically significant interactions also after its intravenous administration.
      The use of oral midazolam with voriconazole should be avoided, or substantially
      lower doses should be used.

PMID- 16580905
TI  - Analgesic effect of acetaminophen in humans: first evidence of a central
      serotonergic mechanism.
AB  - OBJECTIVES: Preclinical studies have suggested that the mechanism of the
      analgesic action of acetaminophen (INN, paracetamol) is linked to the
      serotonergic system and that it is inhibited by tropisetron, a 5
      hydroxytryptamine type 3 antagonist. The aim of this study was to confirm these
      findings in humans. METHODS: Twenty-six rapid metabolizers of tropisetron were
      included in this double-blind crossover study. After ethical approval, at weekly
      intervals, the subjects took a single oral dose of 1 g acetaminophen combined
      with either intravenous tropisetron (5 mg), granisetron (3 mg), or placebo
      (saline solution). For each session, the analgesic effect of acetaminophen was
      assessed by use of a pain self-evaluation instrument, the Pain Matcher. The pain
      detection threshold was determined 5 times over the period of the 4 postdosing
      hours. The area under the curve (0-4 hours) (mean +/- SD) of
      acetaminophen/tropisetron and the area under the curve of
      acetaminophen/granisetron were compared with the effect of acetaminophen/placebo.
      Blood samples for acetaminophen concentration measurements were taken to evaluate
      a pharmacokinetic interaction. RESULTS: The analgesic effect of
      acetaminophen/placebo (expressed as the area under the curve of the percentage of
      the individual pain score reported at baseline along time [% x min]) (2145 +/-
      2901 % x min) was totally inhibited by both tropisetron (89 +/- 1747 % x min, P =
      .007) and granisetron (45 +/- 2020 % x min, P = .002). Acetaminophen
      concentration was not significantly different when associated with tropisetron (P
      = .919) or granisetron (P = .309). CONCLUSION: These results clearly show for the
      first time in humans that the coadministration of tropisetron or granisetron with
      acetaminophen completely blocks the analgesic effect of acetaminophen. They
      support the hypothesis that the mechanism of the analgesic action of
      acetaminophen might involve the serotonergic system. Furthermore, they
      demonstrate a pharmacodynamic interaction between these 2 types of drugs, which
      are frequently coadministered, especially in cancer patients.

PMID- 16580906
TI  - A therapeutic substitution policy for proton pump inhibitors: clinical and
      economic consequences.
AB  - OBJECTIVE: With the growing need to provide prescription drug benefits to older
      patients and to contain costs, it will be necessary to direct that coverage so as
      to make expenditures as efficient as possible. We evaluated the clinical and
      economic consequences of coverage restriction for 3 leading proton pump
      inhibitors (PPIs) in a large-scale natural experiment. METHODS: The study design
      was a time-trend analysis in the setting of a provincial drug benefits program in
      British Columbia, Canada. We studied all British Columbia residents aged 66 or
      older (N = 501,104) using linked data on all prescription drug dispensings,
      physician services, and hospitalizations between January 2002 and June 2004. The
      new policy restricted coverage to rabeprazole and required treatment failure with
      a histamine H2 blocker. More widely used PPIs (omeprazole, pantoprazole, and
      lansoprazole) had to be paid for out of pocket, unless the physician requested an
      exemption. The main outcome measures were utilization of PPIs, drug
      discontinuation rates, gastrointestinal hemorrhage rates, and drug expenditures.
      RESULTS: Utilization of the restricted PPIs declined sharply after the policy
      change (-14,850 daily doses per month per 10,000 residents, P < .0001), whereas
      use of the covered PPI increased sharply (+19,300, P < .0001), with 45% of all
      PPI users switching to the covered agent within 6 months. We found no increased
      use of H2 blockers or stopping of gastroprotective drugs. There was no increase
      in the monthly rate of hospitalization for gastrointestinal hemorrhage after the
      PPI restriction (P = .35) even though the study had the power to detect increases
      of 24 events per 10,000 residents with 95% confidence. There was a slight
      increase in physician visits 3 months after the policy change (P = .01) for a 2
      month period when 9% of new rabeprazole users were switched back to a restricted
      PPI. In the first 6 months of the policy change, the provincial health plan saved
      at least 2.9 million Canadian dollars as a result of the policy change.
      CONCLUSIONS: Coverage restriction of 3 leading PPIs led to substantial
      utilization changes and savings, without increased noncompliance or clinical
      complication.

PMID- 16580907
TI  - Severe arrhythmia as a result of the interaction of cetirizine and pilsicainide
      in a patient with renal insufficiency: first case presentation showing
      competition for excretion via renal multidrug resistance protein 1 and organic
      cation transporter 2.
AB  - A 72-year-old woman with renal insufficiency who was taking oral pilsicainide
      (150 mg/d) complained of feeling faint 3 days after she was prescribed oral
      cetirizine (20 mg/d). She was found to have a wide QRS wave with bradycardia. Her
      symptoms were relieved by termination of pilsicainide. The plasma concentrations
      of both drugs were significantly increased during the coadministration, and the
      cetirizine concentration decreased on cessation of pilsicainide despite the fact
      that treatment with cetirizine was continued, which suggested that the fainting
      was induced by the pharmacokinetic drug interaction. A pharmacokinetic study in 6
      healthy male volunteers after a single dose of either cetirizine (20 mg) or
      pilsicainide (50 mg), or both, found that the renal clearance of each drug was
      significantly decreased by the coadministration of the drugs (from 475 +/- 101
      mL/min to 279 +/- 117 mL/min for pilsicainide and from 189 +/- 37 mL/min to 118
      +/- 28 mL/min for cetirizine; P = .008 and .009, respectively). In vitro studies
      using Xenopus oocytes with microinjected human organic cation transporter 2 and
      renal cells transfected with human multidrug resistance protein 1 revealed that
      the transport of the substrates of these transporters was inhibited by either
      cetirizine or pilsicainide. Thus elevated concentrations of these drugs as a
      result of a pharmacokinetic drug-drug interaction via either human multidrug
      resistance protein 1 or human organic cation transporter 2 (or both) in the renal
      tubular cells might have caused the arrhythmia in our patient. Although
      cetirizine has less potential for causing arrhythmias than other histamine 1
      blockers, such an interaction should be considered, especially in patients with
      renal insufficiency who are receiving pilsicainide.

PMID- 16580910
TI  - Pathology of malignant and premalignant oral epithelial lesions.
AB  - Oral mucous membranes and the surrounding structures are largely composed of
      stratified squamous epithelium that is supported by a fibrous connective tissue
      lamina propria and a submucosa of fibroadipose tissue. Minor salivary glands,
      nerves, and capillaries course abundantly throughout the supporting collagen and
      fibro-fatty submucosa. Premalignant and malignant lesions arise most frequently
      from epithelium, and these epithelial lesions ultimately account for 95% of all
      cancers of the oral cavity. Malignant neoplasia of bone, cartilage, salivary
      glands, and connective tissue and those of lymphoproliferative derivatives are
      far less common occurrences in the oral cavity. Malignant neoplasms can and do
      arise from the tooth germ apparatus, but neoplasms of odontogenic elements are
      rare and are not included in this discussion.

PMID- 16580909
TI  - Molecular biology of oral cavity squamous cell carcinoma.
AB  - Significant advances have been made in understanding the mechanisms that
      contribute to carcinogenesis in OCSCC. This progress has led to the development
      of therapeutic strategies that target dysregulated processes in the tumor
      microenvironment (Fig. 11) [72]. The introduction of angiogenesis inhibitors,
      growth factor receptor tyrosine kinase inhibitors, and cell cycle regulators into
      clinical trials for the management of OCSCC has resulted from the great strides
      made in the understanding of tumor biology. It is important for those caring for
      patients who have OCSCC to have a firm background in tumor biology, because many
      future therapies will be based on this complex panorama of cellular physiology.

PMID- 16580911
TI  - An overview of epidemiology and common risk factors for oral squamous cell
      carcinoma.
AB  - Understanding the epidemiologic picture and the risk factors for oral cancer can
      help identify and treat patients at risk for oral cancers. Early diagnosis of an
      oral cancer continues to be important to achieving a favorable prognosis. Absent
      a diagnosis of oral/pharyngeal cancer, there clearly can-lot be an effective
      treatment plan. Discovering a potentially malignant or malignant lesion and
      through biopsy reaching a diagnosis for the lesion begins by performing an
      examination with the purpose of detecting oral/pharyngeal lesions. An oral cancer
      screening can be performed in less than five minutes without any expensive
      diagnostic aids. Despite the ease with which this exam can be performed and the
      noninvasive nature of the examination,most patients report that they have never
      had an oral cancer examination. Late stage diagnosis continues to be a common
      situation resulting in high rates of morbidity and mortality. Without early
      recognition it seems that the trend of late stage diagnosis will continue.
      Physicians, dentists, and other health care providers should be performing the
      oral cancer screening examination on a routine basis for all of their
      patients.Note: For the interested clinician, the author highly recommends an
      excellent comprehensive text on the subject of oral cancer. Sol Silverman's(with
      multiple contributors) The American Cancer Society's Atlas of Clinical Oncology
      Oral Cancer: Fifth Edition by BC Decker Publishers is an excellent overview of
      oral cancer covering in greater detail many of the subjects that could not be
      covered in this brief article. Additionally, there are excellent color
      photographs of the common presentations of oral malignancies that can be helpful
      in assessing oral/pharyngeal lesions.

PMID- 16580912
TI  - Early diagnosis of oral cavity cancers.
AB  - Dentists, primary care physicians, and otolaryngologists should continue to
      perform complete oral cavity examinations and should be aware of high-risk
      populations for oral cavity carcinomas. Oral cavity carcinoma is the sixth most
      common cancer and is often detected in later stages. By using the modalities of
      physical examination, brush biopsies, vital staining, and spectral analysis, it
      is hoped that more cancers will be detected at an early stage, decreasing the
      morbidity and mortality of oral cavity tumors.

PMID- 16580913
TI  - Imaging of oral cancer.
AB  - This article reviews imaging modalities commonly used to evaluate oral cavity
      cancers and their metastases to lymph nodes. It discusses how the studies are
      performed and their relative merits. It also presents new techniques for
      evaluating these neoplasms.

PMID- 16580914
TI  - Dental considerations in the management of head and neck cancer patients.
AB  - The text has emphasized the need for a timely dental consult early in the process
      of the head and neck cancer patient's treatment. Nonrestorable diseased teeth
      should be removed before radiation and chemotherapy. The primary survey of the
      patient should include an examination of the oral cavity, noting the state of the
      dentition and periodontal tissues. Complications commonly seen in patient's
      undergoing radiotherapy,such as xerostomia, mucositis, and trismus, may be
      reduced and, therefore,improve the patient's quality of life. Optimizing the
      patient's oral health benefits the patient's postsurgical and postirradiation
      course. The dental health care professional can serve an important role in the
      overall outcome of the patient's care.

PMID- 16580915
TI  - The surgical management of oral cancer.
AB  - Oral cavity cancers represent an area of head and neck oncology with some unique
      and interesting management themes. In spite of a significant paradigm shift in
      the treatment of many head and neck cancers toward us-ing primary chemoradiation,
      this treatment is not frequently applied to the oral cavity. Small cancers of the
      oral cavity are usually managed by surgery alone. Larger cancers are usually
      treated with primary surgery followed by chemoradiation. Neck treatment is
      offered to patients who have a greater than 20% chance of having lymph node
      metastasis or who have neck disease at the time of presentation. Neck treatment
      may involve surgery, radiation therapy, or both. Reconstruction of surgical
      defects of the oral cavity runs the gamut of techniques from the most simple to
      the most complex three-dimensional microvascular composite flaps. A
      multidisciplinary setting with a tumor board and multiple supportive services
      provides the best care for patients who have advanced-stage cancers.

PMID- 16580916
TI  - Chemoprevention of squamous cell carcinoma of the oral cavity.
AB  - Squamous cell carcinoma of the oral cavity has long been seen as an attractive
      candidate for chemoprevention strategies. Because of the poor out-comes
      associated with the disease, the presence of identifiable premalignant lesions,
      and the failure of local preventive therapies, such as surgery, many
      investigators have hoped to find an effective chemopreventive compound. Initial
      enthusiasm surrounding high-dose retinoids gave way to concerns regarding
      toxicity and short duration of response. Although many of the other agents
      discussed above have shown promise, as yet none have been proven safe and
      effective in large-scale randomized trials. Much has been learned,however, about
      the molecular process of oral carcinogenesis from studies of these agents.
      Ongoing and future studies of chemopreventive agents in oral cancer hopefully
      will be able to exploit our expanding knowledge of these molecular pathways.

PMID- 16580917
TI  - Current radiation therapy management issues in oral cavity cancer.
AB  - Oral cavity cancer presents a therapeutic challenge to the treating
      surgeons,radiation oncologists, and medical oncologists. In early-stage disease,
      surgery or radiation alone often achieves excellent local control. Patients who
      have risk factors for recurrence after surgery should undergo adjuvant
      radiotherapy or chemoradiotherapy. In locally advanced disease, recurrence rates
      and deaths caused by disease progression continue to be unacceptably high. During
      the past decade, multiple randomized studies have shown a benefit in the addition
      of chemotherapy to radiation in the definitive or postoperative setting. Also,
      hyperfractionated and concomitant boost radiotherapy has shown superior results
      when compared with conventional once-daily radiotherapy. The addition of
      chemotherapy to hyperfractionated or concomitant boost radiotherapy also seems to
      improve outcomes at the cost of increased toxicities. In addition to traditional
      therapeutic modalities, new targeted agents seem promising to improve outcomes
      and possibly allow use of decreased doses of chemotherapy or radiotherapy, thus
      decreasing the toxicity of treatment.Overall, the management of cancer of the
      oral cavity is evolving rapidly,and a multidisciplinary approach to the patient
      who has oral cavity cancer is important to ensure the highest quality of patient
      care.

PMID- 16580919
TI  - Current practice in pediatric surgery.

PMID- 16580918
TI  - Future directions in the treatment of oral cancer.
AB  - Future developments in the realms of nanotechnology and directed therapeutics
      will alter the diagnosis and treatment of oral cancer relative to contemporary
      treatment modalities. Continued experience and investigation will determine the
      clinical usefulness of the various technologies that have been described in this
      article.

PMID- 16580921
TI  - Neonatal and childhood perioperative considerations.

PMID- 16580922
TI  - Gastroschisis and omphalocele.

PMID- 16580923
TI  - Foregut abnormalities.

PMID- 16580924
TI  - Midgut abnormalities.

PMID- 16580925
TI  - Hindgut abnormalities.

PMID- 16580926
TI  - Pediatric surgical issues in meconium disease and cystic fibrosis.

PMID- 16580927
TI  - Congenital diaphragmatic hernia and neonatal lung lesions.

PMID- 16580928
TI  - Congenital chest wall defects.

PMID- 16580929
TI  - Inguinal and scrotal disorders.

PMID- 16580930
TI  - Congenital neck lesions.

PMID- 16580931
TI  - Vascular anomalies.

PMID- 16580932
TI  - Surgical management of pediatric hematologic disorders.

PMID- 16580933
TI  - Adolescent obesity and bariatric surgery.

PMID- 16580934
TI  - Hepatobiliary disorders.

PMID- 16580935
TI  - Pediatric solid malignancies: neuroblastoma and Wilms' tumor.

PMID- 16580936
TI  - Germ cell tumors.

PMID- 16580937
TI  - Bowel management for patients with myelodysplasia.

PMID- 16580938
TI  - Bladder management for patients with myelodysplasia.

PMID- 16580940
TI  - Rubella infection in pregnancy.
AB  - Rubella is the first virus demonstrated as a teratogen. There is a high risk to
      develop congenital rubella syndrome (CRS) if the infection occurs in the first
      part of pregnancy, particularly in women without specific immunological
      protection. Specific therapies to prevent CRS are not available. Many developed
      countries have specific vaccination programs and maternal rubella is rare.
      However, in developing countries or where campaigns of rubella surveillance and
      preconceptional vaccination are inadequate, there are still cases of CRS
      registered despite primary possibilities of prevention. Maternal infection is not
      indicative of vertical transmission in 100% of cases, and damage does not
      necessarily occur in all cases of fetal infection. This is the reason why an
      adequate prenatal counselling is mandatory, particularly in cases of proven
      maternal infection. Advanced prenatal diagnostic techniques, invasive or not,
      should be offered to the women especially in order to distinguish the cases
      without fetal damage. Prevention of voluntary interruption of pregnancy for the
      latter or in case of maternal false IgM rubella antibody positivity or IgM
      "chronic carrier" patients is mandatory. World wide, the aim is to perform an
      adequate primary prevention through vaccination of childbearing age women without
      specific immunological protection.

PMID- 16580941
TI  - Fetal effects of primary and secondary cytomegalovirus infection in pregnancy.
AB  - Seroconversion to cytomegalovirus (CMV) occurs in 1-4% of pregnant women. The
      majority of these women are seropositive prior to pregnancy. In 0.2-2.5% of the
      newborn infants, there is evidence of intrauterine infection, most of them are
      born without any clinical findings. The typical clinical symptoms of congenital
      CMV (symptomatic congenital CMV) that are found in 10-20% of infected neonates
      include intrauterine growth restriction (IUGR), microcephaly, hepatosplenomegaly,
      petechiae, jaundice, chorioretinitis, thrombocytopenia, anemia and/or other
      atypical findings. Of special problem are the different neurodevelopmental
      sequelae such as mental retardation, motor impairment, sensorineural hearing loss
      or visual impairment, which may occur even in infants who are free of symptoms at
      birth. Most infants born with severe neonatal symptoms of congenital CMV are born
      to mothers with primary infection in pregnancy. However, since over 60% of the
      infants infected in utero with CMV are born to mothers with preconceptional
      immunity who have secondary infection in pregnancy, and more and more studies
      show severe sequelae in these infants, we have to conclude that congenital CMV
      may be a significant problem even in children born to mothers with pre-pregnancy
      immunization. This may justify the use of invasive methods for the detection of
      possible fetal infection even in cases of secondary CMV infection. This also
      brings in an additional problem, when considering the need for proper
      immunization against CMV, as immunization is primarily aimed for women without
      immunity.

PMID- 16580942
TI  - Parvovirus B19 in pregnancy.
AB  - Parvovirus B19 is a widespread infection that may affects 1-5% of pregnant women,
      mainly with normal pregnancy outcome. The prevalence of infection is higher
      during epidemics - between 3 and 20% with sero-conversion rate of 3-34%.
      Infection during pregnancy can cause a variety of other signs of fetal damage.
      The risk of adverse fetal outcome is increased if maternal infection occurs
      during the first two trimesters of pregnancy but may also happen during the third
      trimester. It is a significant cause of fetal loss throughout pregnancy, but has
      a higher impact in the second half of pregnancy when spontaneous fetal loss from
      other causes is relatively rare. Parvovirus infection can cause severe fetal
      anemia as a result of fetal erythroid progenitor cells infection with shortened
      half life of erythrocytes, causing high output cardiac failure and therefore
      nonimmune hydrops fetalis (NIHF). The P antigen expressed on fetal cardiac
      myocytes enables the Parvovirus B19 to infect myocardial cells and produce
      myocarditis that aggravates the cardiac failure. Although there are several
      reports of major congenital anomalies among offspring of mothers infected by
      Parvovirus, the virus does not seem to be a significant teratogen. Since
      Parvovirus B19 infection can cause severe morbidity and mortality, it should be
      part of the routine work up of complicated pregnancies. Risk assessment for
      maternal infection during pregnancy is especially important during epidemics when
      sero-conversion rates are high.

PMID- 16580943
TI  - Herpes simplex virus and Epstein-Barr virus infections in pregnancy: consequences
      of neonatal or intrauterine infection.
AB  - Herpes simplex virus (HSV) type 1/2 and Epstein-Barr virus (EBV) belong to the
      human herpes viruses and are among the most ubiquitous viruses in the adult
      population. In spite of the fact that a large proportion of women at childbearing
      age are seropositive to these viruses, especially to HSV, primary or secondary
      infections with these viruses may occur during pregnancy. Genital HSV, especially
      in primary infections, may be dangerous to the neonate if infected during
      delivery, as it can cause a severe neonatal disease. Intrauterine infection
      causing abortion or stillbirth as well as skin scars (cutaneous manifestations),
      ophthalmologic findings (chorioretinitis, microphtalmia), and neurological
      involvement (causing brain damage) is also possible, but relatively rare. Primary
      infection with EBV during pregnancy with apparent transplacental transmission is
      rare and only few cases were reported. They main damage was in the heart, eyes
      and liver. The actual damage to the developing embryo and fetus from maternal HSV
      and EBV seems to be very small. It should be mentioned that both HSV and EBV seem
      to be able to cross the placenta and cause, as described by several
      investigators, placental infection manifested by deciduitis and villitis. These
      placental pathological changes may increase fetal damage.

PMID- 16580944
TI  - Consequences of being medically uninsured.

PMID- 16580946
TI  - Integrated cardiac PET-CT for the diagnosis and management of CAD.

PMID- 16580947
TI  - Positron emission tomography and magnetic resonance imaging in heart failure.

PMID- 16580948
TI  - Coronary artery disease and nuclear imaging in renal failure.

PMID- 16580949
TI  - Role of noninvasive imaging in asymptomatic high-risk patients.

PMID- 16580950
TI  - Role of nuclear imaging after coronary revascularization.

PMID- 16580951
TI  - Role of computed tomography and perfusion imaging in patients with known or
      suspected coronary artery disease.

PMID- 16580952
TI  - One size fits all?

PMID- 16580953
TI  - Assessment of myocardial viability: more than measurements of radiotracer uptake
      alone.

PMID- 16580954
TI  - Monitoring effectiveness of medical therapy in 2006.

PMID- 16580955
TI  - Diagnostic accuracy of gated Tc-99m sestamibi stress myocardial perfusion SPECT
      with combined supine and prone acquisitions to detect coronary artery disease in
      obese and nonobese patients.
AB  - BACKGROUND: The diagnostic value of gated myocardial perfusion single-photon
      emission computed tomography (MPS) with combined supine and prone acquisitions to
      detect coronary artery disease (CAD) in obese and nonobese patients has not been
      defined. METHODS AND RESULTS: We studied 1511 patients without prior myocardial
      infarction or coronary revascularization who either had coronary angiography
      within 3 months of MPS (n = 785) or had a low pretest likelihood of CAD (n =
      726). All patients underwent rest thallium 201/gated exercise or adenosine stress
      technetium 99m sestamibi MPS in both the supine and prone positions. According to
      body mass index (BMI), patients were categorized as normal weight (BMI of 18.5
      24.9 kg/m2), overweight (BMI of 25.0-29.9 kg/m2), or obese (BMI > or = 30.0
      kg/m2). There were no significant differences in stress, fixed, or ischemic
      defects among patients in different weight categories. The sensitivity of MPS was
      85%, 86%, and 89% for detecting patients with 50% or greater coronary stenosis
      and 89%, 91%, and 92% for detecting those with 70% or greater coronary stenosis
      in the normal-weight, overweight, and obese groups, respectively. Normalcy rates
      were nearly identical among the 3 weight groups (99%, 98%, and 99%,
      respectively). Multivariate logistic regression analysis further confirmed that
      BMI was a nonsignificant predictor for the detection of CAD. In a subset of 290
      patients, automated quantitative MPS analysis confirmed that combined supine and
      prone MPS increased specificity (86%) in identifying CAD, without a significant
      reduction in sensitivity (83% for > or = 50% stenosis and 88% for > or = 70%
      stenosis). CONCLUSION: The findings of this study suggest that MPS performed with
      gating and combined supine and prone acquisitions without attenuation correction
      had a similar diagnostic accuracy for the detection of CAD in normal-weight,
      overweight, and obese patients.

PMID- 16580956
TI  - SPECT myocardial perfusion imaging in morbidly obese patients: image quality,
      hemodynamic response to pharmacologic stress, and diagnostic and prognostic
      value.
AB  - BACKGROUND: Obesity is a growing epidemic in the United States, and little is
      known about the characteristics of the morbidly obese population (body mass index
      [BMI] > or = 40 kg/m2) undergoing stress myocardial perfusion imaging (MPI).
      METHODS AND RESULTS: We retrospectively reviewed all consecutive morbidly obese
      patients without known coronary artery disease presenting for a clinically
      indicated technetium 99m (Tc-99m) gated stress single photon emission computed
      tomography imaging study over a 42-month period. Studies were analyzed for image
      quality, for the contribution of attenuation correction to image interpretation,
      and for the hemodynamic response to pharmacologic stress. In patients who
      subsequently had cardiac catheterization, the results were compared with those
      from the initial MPI study, and the Social Security Death Index and hospital
      medical records were searched to the assess survival rate in the entire cohort. A
      total of 433 patients were identified with a mean BMI of 47.3 +/- 8 kg/m2 and a
      mean Tc-99m stress dose of 35.6 +/- 5.4 mCi. Image quality was good in 61% of the
      patients, adequate in 37%, and poor in 2%. It was found to be dependent on the
      stressor used (better with exercise) but did not correlate with increasing weight
      or BMI. Attenuation correction was used in 95% of the studies reviewed and was
      helpful for image interpretation in 60%. The heart rate response to dipyridamole
      and adenosine was more pronounced and the blood pressure response to dipyridamole
      was less pronounced in morbidly obese patients compared with nonobese control
      patients. In the 43 patients who underwent catheterization, stress MPI had a
      sensitivity of 95% and negative predictive value of 80%. Kaplan-Meier survival
      analysis at 1 year showed a significant difference in survival rate of 98.3% for
      normal MPI studies and 94.0% for abnormal MPI studies (P = .02). CONCLUSION:
      Diagnostic-quality single photon emission computed tomography imaging is feasible
      in the majority (98%) of morbidly obese patients with the use of a dual-head
      camera, attenuation correction, and high stress Tc-99m tracer doses. Exercise
      stress was associated with better image quality. The prognostic value of a normal
      MPI study in this population appears to be less favorable than in non-morbidly
      obese patients.

PMID- 16580958
TI  - Direct comparison between 2-dimensional and 3-dimensional PET acquisition modes
      for myocardial blood flow absolute quantification with O-15 water and N-13
      ammonia.
AB  - BACKGROUND: Positron emission tomography scanners with retractable septa allow
      both 3-dimensional (3D) and 2-dimensional (2D) acquisition modes. The study aim
      was to directly compare 2D and 3D acquisition modes for the evaluation of
      absolute myocardial blood flow (MBF) over a wide range of flow values. METHODS
      AND RESULTS: Instrumentation was used in 4 dogs to reduce the left circumflex
      artery lumen by greater than 75%. During infusion of adenosine, MBF was measured
      with both 2D and 3D dynamic acquisition and both oxygen 15 water and nitrogen 13
      ammonia. Injected activities were 333 MBq and 111 MBq for 2D acquisition and 3D
      acquisition, respectively. Data were reconstructed by analytic methods, and MBF
      was assessed by use of an 18-segment model. MBF values ranged from 0.4 to 5.8 mL
      x g(-1) x min(-1) with O-15 water and from 0.3 to 3.9 mL x g(-1) x min(-1) with N
      13 ammonia. No significant differences were observed in absolute MBF values
      obtained with the 2 acquisition modes, regardless of the flow tracer used. Two
      dimensionally and three-dimensionally derived MBF values were significantly
      strongly correlated by use of both O-15 water (y = 0.98x + 0.18, r = 0.87, P <
      .001) and N-13 ammonia (y = 0.99x + 0.09, r = 0.95, P < .001). CONCLUSION:
      Quantification of MBF in dogs with 3D positron emission tomography provides
      results similar to those obtained with the 2D technique, despite a lower activity
      being injected.

PMID- 16580957
TI  - Prediction of functional recovery after revascularization in patients with
      coronary artery disease and left ventricular dysfunction by gated FDG-PET.
AB  - BACKGROUND: Traditionally, cardiac fluorodeoxyglucose (FDG) uptake is combined
      with regional perfusion for optimal evaluation of viability. Gated FDG-positron
      emission tomography (PET) may be an alternative technique for detection of
      viability because it permits combined assessment of glucose metabolism uptake and
      wall thickening (WT). In this study the value of FDG uptake and WT (analyzed from
      a stand-alone gated FDG-PET study) for the prediction of recovery of regional and
      global left ventricular (LV) function in patients with coronary artery disease
      undergoing revascularization is studied. METHODS AND RESULTS: Thirty-eight
      patients with chronic coronary artery disease and LV dysfunction were included.
      Patients underwent gated FDG-PET to assess viability. Magnetic resonance imaging
      was performed before and 6 months after revascularization to assess regional and
      global LV function and LV volumes. Of the 213 revascularized dysfunctional
      segments, 133 (62%) exhibited functional recovery on follow-up magnetic resonance
      imaging. Receiver operating characteristic curve analysis indicated that a cutoff
      level for FDG uptake of 50% or greater yielded a sensitivity and specificity of
      93% and 85%, respectively, on gated FDG-PET for prediction of improvement in
      regional function. Similarly, a cutoff level of 10% or greater for WT was optimal
      with a sensitivity and specificity of 89% and 78%, respectively. Improvement in
      LV ejection fraction was best predicted by the number of viable segments. Reverse
      LV remodeling could be predicted with a sensitivity and specificity of 89% and
      65%, respectively, by use of FDG uptake of 50% or greater and 78% and 70%,
      respectively, by use of WT of 10% or greater. CONCLUSION: Accurate prediction of
      outcome after revascularization (including improvement in regional and global LV
      function and reverse remodeling) is possible with gated FDG-PET by use of a
      threshold of 50% or greater for FDG uptake or a threshold of 10% or greater for
      WT.

PMID- 16580959
TI  - Worsening of left ventricular ejection fraction induced by dipyridamole on Tl-201
      gated myocardial perfusion imaging predicts significant coronary artery disease.
AB  - BACKGROUND: Vasodilator stress on myocardial perfusion imaging has been found to
      induce ischemic stunning, which may present as transient worsening of left
      ventricular ejection fraction (LVEF) or regional wall motion abnormality. This
      study aimed to evaluate the significance of stress-induced worsening of LVEF in
      the diagnosis of coronary artery disease (CAD) on dipyridamole thallium 201 gated
      single photon emission computed tomography (SPECT). METHODS AND RESULTS: The
      study included 126 patients who underwent dipyridamole Tl-201 gated SPECT and
      coronary angiography within 3 months. Poststress and 4-hour rest images were
      obtained, and LVEF was calculated by use of automated software (QGS 3.0). A
      decrease in LVEF of 6% or greater from rest to poststress was considered
      significant, and this threshold was determined by the serial reproducibility
      assessment of Tl-201 gated SPECT. If worsening of LVEF was used as the criterion
      for detecting significant CAD (> or = 70% coronary stenoses in > or = 1 vessel),
      the sensitivity, specificity, positive predictive value, and negative predictive
      value were 35%, 93%, 90%, and 44%, respectively. CONCLUSION: Dipyridamole-induced
      worsening of LVEF, as shown by Tl-201 gated SPECT, is a valuable nonperfusion
      marker of significant CAD. Although the sensitivity of LVEF worsening in
      detecting significant CAD is only 35%, the specificity is as high as 93%.

PMID- 16580960
TI  - Comparison of interstudy reproducibility of equilibrium electrocardiography-gated
      SPECT radionuclide angiography versus planar radionuclide angiography for the
      quantification of global left ventricular function.
AB  - BACKGROUND: Electrocardiography-gated single photon emission computed tomography
      (SPECT) radionuclide angiography (RNA) provides accurate measurement of both left
      ventricular (LV) ejection fraction (EF) and end-diastolic and end-systolic
      volumes. In this study we studied the interstudy precision and reliability of
      SPECT RNA as compared with planar RNA for the measurement of global systolic LV
      function. METHODS AND RESULTS: The population included 10 patients with chronic
      coronary artery disease having 2 sets of acquisitions, each consisting of planar
      and SPECT RNA. SPECT RNA was processed with SPECT-QBS and SPECT-35%. (For SPECT
      35%, a manual segmentation method based on the 35% threshold of the maximum LV
      cavity activity is used to provide estimates of the number of voxels and the
      activity included in the LV cavity. The calculated LV number of voxels is then
      used to calculate LV volume measurement. The LV EF is calculated as the ratio of
      LV end-diastolic and end-systolic activity.) For LV EF, end-diastolic volume, and
      end-systolic volume, the interstudy precision, as reflected by the correlation
      coefficient, coefficient of variability, coefficient of repeatability, and within
      subject coefficient of variation, and the interstudy reliability, as reflected by
      the intraclass correlation coefficient, were best with SPECT-35%, followed by
      planar RNA and then SPECT-QBS, respectively. The sample size needed to objectify
      a change in a parameter of LV function is lowest with SPECT-35%, followed by
      planar RNA and then SPECT-QBS, respectively. CONCLUSIONS: The SPECT-35%
      processing method provides excellent interstudy precision and reliability for LV
      function measurement. In this aspect it seems to be better than planar RNA and
      SPECT-QBS. These results need to be confirmed in a larger patient population.

PMID- 16580961
TI  - Acute impairment of regional myocardial glucose uptake in the apical ballooning
      (takotsubo) syndrome.
AB  - BACKGROUND: Apical ballooning syndrome (ABS) is a poorly understood clinical
      entity characterized by acute, transient systolic dysfunction of the left
      ventricular (LV) apex in the absence of epicardial coronary artery disease and
      commonly associated with acute emotional stress. We report abnormal regional
      myocardial perfusion and glucose uptake in 4 consecutive ABS patients studied
      using positron emission tomography with 13N-ammonia and 18F-fluorodeoxyglucose
      within 72 hours of presentation with ABS. METHODS: All patients were
      postmenopausal females, 3 of whom had a major recent life stress event. Coronary
      angiography revealed no or minimal obstructive epicardial coronary artery
      disease. All patients exhibited reduced glucose uptake in the mid-LV and apical
      myocardial segments, which was out of proportion to perfusion abnormalities in
      half of the cases. CONCLUSION: In all 4 patients, affected regions subsequently
      recovered regional LV systolic function within 6 weeks.

PMID- 16580962
TI  - Optimized acquisition and processing protocols for I-123 cardiac SPECT imaging.
AB  - BACKGROUND: Deconvolution of septal penetration (DSP) has been developed to
      improve quantification so as to allow the use of low-energy high-resolution
      collimators for iodine 123 cardiac single photon emission computed tomography
      (SPECT) imaging. The purpose of this study is to optimize its acquisition and
      processing protocols. METHODS AND RESULTS: Planar images of a 9-compartment
      phantom loaded with variable radioactive concentrations were acquired to derive
      optimal scatter compensation scaling factors for 20% and 15% photopeak energy
      window configurations, respectively. A cardiac phantom, loaded with high and low
      heart-to-calibration ratios (HCRs), respectively, was imaged with both
      configurations. Repeated acquisitions were done for medium-energy all-purpose
      collimators for comparison. Critical frequencies for Butterworth filtering were
      optimized by use of defect contrast and normal short-axis uniformity as selection
      indices. HCRs were calculated with planar projection and different reconstruction
      methods, respectively, and then compared with the true HCRs. SPECT produced more
      accurate HCRs than planar imaging. With the optimized parameters for scatter
      compensation and filtering, the 2 energy window configurations yielded similar
      results. Iterative reconstructions with DSP yielded more accurate HCRs than other
      reconstructions without DSP. CONCLUSION: The optimized protocols based on DSP
      show promise that quantification of I-123 cardiac SPECT imaging can be achieved
      with the widely available low-energy high-resolution collimators.

PMID- 16580965
TI  - Permanently increased brightness of right ventricle (D-shaped left ventricle) on
      myocardial perfusion imaging in a patient with chronic cor pulmonale: an autopsy
      correlation.

PMID- 16580964
TI  - Echocardiographic assessment of left ventricular function.

PMID- 16580966
TI  - Hepatobiliary abnormalities on nuclear perfusion imaging.

PMID- 16580963
TI  - Gated SPECT in assessment of regional and global left ventricular function: major
      tool of modern nuclear imaging.

PMID- 16580967
TI  - Assessment of flow-mediated vasodilation.

PMID- 16580969
TI  - Critical review of the role of HTS in drug discovery.
AB  - 'A wise use of lead discovery tactics will distinguish successful drug discovery
      engines.'

PMID- 16580970
TI  - Medicinal chemistry strategies to 5-HT(6) receptor ligands as potential cognitive
      enhancers and antiobesity agents.
AB  - Although the 5-hydroxytryptamine(6) (5-HT(6)) receptor was discovered only
      recently, its almost exclusive distribution in the brain makes it a promising,
      novel, target for central nervous system (CNS)-mediated diseases such as
      Alzheimer's disease (cognitive function), schizophrenia, anxiety and obesity. In
      the past few years a significant research interest has advanced the understanding
      of the functional roles and the pharmacophore requirements of this receptor. Two
      5-HT(6) receptor antagonists have already entered Phase II clinical trials for
      the enhancement of cognitive function. Since the first discovery of selective
      ligands for the 5-HT(6) receptor by HTS in 1998, several medicinal-chemistry
      driven approaches have delivered highly selective lead structures with well
      defined functionalities, starting from either the endogenous ligand 5-HT or the
      chemical structures identified by HTS. The concept of 'scaffold hopping' has been
      employed to expand the variability of the available chemical scaffolds and to
      generate patentable ligands. Supported by pharmacophore models, which have been
      established recently, the binding and functionality (structure-activity
      relationships) of the lead structures have been optimized further.

PMID- 16580971
TI  - Orphan enzymes could be an unexplored reservoir of new drug targets.
AB  - Despite the immense progress of genomics, and the current availability of several
      hundreds of thousands of amino acid sequences, >39% of well-defined enzyme
      activities (as represented by enzyme commission, EC, numbers) are not associated
      with any sequence. There is an urgent need to explore the 1525 orphan enzymes
      (enzymes having EC numbers without an associated sequence) to bridge the wide gap
      that separates knowledge of biochemical function and sequence information.
      Strikingly, orphan enzymes can even be found among enzymatic activities
      successfully used as drug targets. Here, knowledge of sequence would help to
      develop molecular-targeted therapies, suppressing many drug-related side-effects.

PMID- 16580972
TI  - The cryptome: a subset of the proteome, comprising cryptic peptides with distinct
      bioactivities.
AB  - There is increasing evidence that proteolytic cleavage gives rise to 'hidden'
      peptides with bioactivities that are often unpredicted and totally distinct to
      the parent protein. So far, the liberation of these cryptic peptides, or
      crypteins, has been shown to be prevalent in proteins associated with endocrine
      signalling, the extracellular matrix, the complement cascade and milk. A broad
      spectrum of proteases has been implicated in the generation of natural crypteins
      that appear to play a role in modulating diverse biological processes, such as
      angiogenesis, immune function and cell growth. The proteolytic liberation of
      crypteins with novel activities represents an important mechanism for increasing
      diversity of protein function and potentially offers new opportunities for
      protein-based therapeutics.

PMID- 16580973
TI  - Status of text-mining techniques applied to biomedical text.
AB  - Scientific progress is increasingly based on knowledge and information. Knowledge
      is now recognized as the driver of productivity and economic growth, leading to a
      new focus on the role of information in the decision-making process. Most
      scientific knowledge is registered in publications and other unstructured
      representations that make it difficult to use and to integrate the information
      with other sources (e.g. biological databases). Making a computer understand
      human language has proven to be a complex achievement, but there are techniques
      capable of detecting, distinguishing and extracting a limited number of different
      classes of facts. In the biomedical field, extracting information has specific
      problems: complex and ever-changing nomenclature (especially genes and proteins)
      and the limited representation of domain knowledge.

PMID- 16580974
TI  - Integrating molecular design resources within modern drug discovery research: the
      Roche experience.
AB  - Various computational disciplines, such as cheminformatics, ADME modeling,
      virtual screening, chemogenomics search strategies and classic structure-based
      design, should be seen as one multifaceted discipline contributing to the early
      drug discovery process. Although significant resources enabling these activities
      have been established, their true integration into daily research should not be
      taken for granted. This article reviews value-adding activities from target
      assessment to lead optimization, and highlights the technical and process-related
      aspects that can be considered essential for performance and alignment within the
      research organization.

PMID- 16580975
TI  - Peptide aptamers as guides for small-molecule drug discovery.
AB  - Peptide aptamers are combinatorial protein reagents that bind to target proteins
      with a high specificity and a strong affinity. By so doing, they can modulate the
      function of their cognate targets. Because peptide aptamers introduce
      perturbations that are similar to those caused by therapeutic molecules, their
      use identifies and/or validates therapeutic targets with a higher confidence
      level than is typically provided by methods that act upon protein expression
      levels. The unbiased combinatorial nature of peptide aptamers enables them to
      'decorate' numerous polymorphic protein surfaces, whose biological relevance can
      be inferred through characterization of the peptide aptamers. Bioactive aptamers
      that bind druggable surfaces can be used in displacement screening assays to
      identify small-molecule hits to the surfaces. The peptide aptamer technology has
      a positive impact on drug discovery by addressing major causes of failure and by
      offering a seamless, cost-effective process from target validation to hit
      identification.

PMID- 16580977
TI  - Similarity in drugs: reflections on analogue design.
AB  - A survey of novel small-molecule therapeutics reveals that the majority of them
      result from analogue design and that their market value represents two-thirds of
      all small-molecule sales. In natural science, the term analogue, derived from the
      Latin and Greek analogia, has always been used to describe structural and
      functional similarity. Extended to drugs, this definition implies that the
      analogue of an existing drug molecule shares structural and pharmacological
      similarities with the original compound. Formally, this definition allows the
      establishment of three categories of drug analogues: analogues possessing
      chemical and pharmacological similarities (direct analogues); analogues
      possessing structural similarities only (structural analogues); and chemically
      different compounds displaying similar pharmacological properties (functional
      analogues).

PMID- 16580976
TI  - Cell-surface and cytokine biomarkers in autoimmune and inflammatory diseases.
AB  - Increasing emphasis is being placed on biomarkers as indicators of disease states
      in patients with autoimmune and inflammatory disorders, such as rheumatoid
      arthritis, multiple sclerosis and systemic lupus erythematosus. Careful
      description of the expression of cell-surface markers and cytokines produced by T
      and B lymphocytes can lead to a more complete characterization of disease
      activity in patient populations, and serve as an indicator of the patient's
      response to therapy.

PMID- 16580978
TI  - Strategies to optimize the validity of disease models in the drug discovery
      process.
AB  - Models of human diseases are necessary for experimental research into the
      biological basis of disease and for the development of treatments. They have an
      enormous impact upon the success of biomedical research. However, in spite of
      this, a consistent system for evaluating, expressing and comparing the clinical
      validity of disease models is not available. The purpose of this paper is,
      therefore, to provide a theoretical discussion of the concepts behind disease
      models and to develop a terminology and a framework to analyze and express the
      clinical validity of disease models.

PMID- 16580979
TI  - Ischemic acute tubular necrosis models and drug discovery: a focus on cellular
      inflammation.
AB  - Acute renal failure (ARF) is a common cause of mortality and morbidity in
      hospitalized patients. Ischemia is an important cause of ARF, and ARF caused by
      ischemic injury is referred to as ischemic acute tubular necrosis (ATN). There is
      growing evidence from models that ischemic ATN is associated with intrarenal
      inflammation. Consequently, intrarenal inflammation is an attractive target for
      the development of novel drug therapies for ARF. This review outlines ischemic
      ATN models, the pathophysiological roles of inflammatory cells such as T and B
      cells in ischemic ATN models, and effective T and B cell therapeutic reagents.

PMID- 16580982
TI  - HIPAA and disaster research: preparing to conduct research.
AB  - The Health Insurance Portability and Accountability Act (HIPAA), enacted in 1996
      and implemented in 2003, continues to have a profound impact on the ability to
      carry out research. Many disaster research methodologies are not affected by the
      HIPAA Privacy Rule and are likely to be appropriate for waivers because of the
      nature of disaster research. Still other types of studies may require special
      considerations that researchers must be aware of when planning research
      methodologies.

PMID- 16580983
TI  - The Sri Lanka tsunami experience.
AB  - The Indian Ocean tsunami of 2004 killed 31,000 people in Sri Lanka and produced
      morbidity primarily resulting from near-drownings and traumatic injuries. In the
      immediate aftermath, the survivors brought bodies to the hospitals, which
      hampered the hospitals' operations. The fear of epidemics led to mass burials.
      Infectious diseases were prevented through the provision of clean water and
      through vector control. Months after the tsunami, little rebuilding of permanent
      housing was evident, and many tsunami victims continued to reside in transit
      camps without means of generating their own income. The lack of an incident
      command system, limited funding, and political conflicts were identified as
      barriers to optimal relief efforts. Despite these barriers, Sri Lanka was
      fortunate in drawing upon a well-developed community health infrastructure as
      well as local and international resources. The need continues for education and
      training in clinical skills for mass rescue and emergency treatment, as well as
      participation in a multidisciplinary response.

PMID- 16580984
TI  - Motivations, concerns, and expectations of Scandinavian health professionals
      volunteering for humanitarian assignments.
AB  - International nongovernmental organizations (NGOs) involved in humanitarian
      assistance employ millions of volunteers. One of the major challenges for the
      organizations is the high turnover rate among their personnel. Another is
      recruiting the right persons. As part of a series of studies investigating
      factors that affect the recruitment process and the success of assignment, this
      qualitative study examined health professionals' motivations for volunteering,
      their various concerns, and their expectations about themselves and the
      organizations for which they would work. The findings from focus group interviews
      with potential humanitarian volunteers were considered within the framework of
      Hertzberg's theory of motivations and Maslow's hierarchy of needs. The study has
      significant implications for personnel policy and practice in the humanitarian
      sector. Recruitment officers should have the self-actualized person, as described
      by Maslow, in mind when interviewing candidates. This perspective would make it
      easier for them to understand the candidates' thoughts and concerns and would
      lead to more effective interventions. Program officers should have satisfiers and
      dissatisfiers, as identified by Herzberg, in mind when planning programs. The
      probability that personnel will leave humanitarian work is lower if they perceive
      working conditions as good.

PMID- 16580985
TI  - Defining "disasters" with implications for nursing scholarship and practice.
AB  - Nurses have long been a part of disaster care, yet the nurses' unique approaches
      to disaster victims have not been reported in the nursing literature. This
      situation raises the questions, "How does disaster nursing differ than general
      nursing?" and "What defines the specialty care of disaster nursing?" An analysis
      of the term "disaster" and the concepts that have been used to build a theoretic
      base for disaster nursing are presented.

PMID- 16580986
TI  - Visualizing the breaking of symmetry.
AB  - Axon specification is a hallmark of neuron polarization. Although several models
      have been proposed, few studies have provided clues about polarization events in
      real time. Using time-lapse imaging, a recent study described visualizing
      symmetry-breaking events during this process.

PMID- 16580987
TI  - Turning off Smads: identification of a Smad phosphatase.
AB  - Although the activation of Smad signaling pathways downstream of TGF-beta
      superfamily ligands by receptor-mediated Smad phosphorylation is well understood,
      nothing is known about Smad phosphatases that turn off Smad activity. Recently in
      Genes & Development, describe pyruvate dehydrogenase phosphatase as a Smad1
      phosphatase that functions in Drosophila in the Decapentaplegic pathway and in
      mammalian cells in the BMP pathway.

PMID- 16580988
TI  - Migration in action: profiling border cells.
AB  - Acquiring the ability to migrate is essential for cells taking part in many
      developmental and disease processes. Two studies in this issue of Developmental
      Cell use gene expression profiling of purified border cells from the Drosophila
      ovary to characterize the molecular changes required in cells to initiate
      migration in vivo. Their results offer interesting new insights into a moving
      cell's physiology.

PMID- 16580989
TI  - Regulating quiescence: new insights into hematopoietic stem cell biology.
AB  - Blood-forming hematopoietic stem cells (HSCs) ensure production of all mature
      blood cells during homeostatic and regenerative hematopoiesis. Proliferation,
      cell cycle regulation, and quiescence are key processes involved in this
      function, and in a recent issue of Cancer Cell, show that HSC quiescence is
      actively regulated by specific molecular mechanisms that appear to distinguish
      normal HSC maintenance from HSC responses to hematologic injury.

PMID- 16580990
TI  - Asymmetric recruitment of dynein to spindle poles and microtubules promotes
      proper spindle orientation in yeast.
AB  - The orientation of the mitotic spindle plays a key role in determining whether a
      polarized cell will divide symmetrically or asymmetrically. In most cell types,
      cytoplasmic dynein plays a critical role in spindle orientation. However, how
      dynein directs opposite spindle poles toward distinct and predetermined cell ends
      is poorly understood. Here, we show that dynein distributes preferentially to the
      spindle pole bodies (SPB) and astral microtubules (MTs) proximal to the bud in
      metaphase yeast cells. Dynein asymmetry depended on the bud neck kinases Elm1,
      Hsl1, and Gin4, on the spindle pole components Cnm67 and Cdk1, and on the B-type
      cyclins Clb1 and Clb2. Furthermore, phenotypic and genetic studies both indicated
      that dynein is unable to orient the spindle when it localizes to both poles and
      associated microtubules. Together, our data indicate that proper orientation of
      the spindle requires dynein to act on a single spindle pole.

PMID- 16580991
TI  - The mouse embryo autonomously acquires anterior-posterior polarity at
      implantation.
AB  - The earliest recognizable sign of patterning of the mouse embryo along the
      anteroposterior (A-P) axis is the migration of the distal visceral endoderm (DVE)
      toward the future anterior side. Here we report an asymmetry in the mouse embryo
      at an unexpectedly early stage. The gene for Lefty1, a Nodal antagonist that
      influences the direction of DVE migration, was found to be asymmetrically
      expressed in the primitive endoderm of the implanting blastocyst. Lefty1
      expression begins randomly in the inner cell mass (ICM) of the blastocyst but is
      regionalized to one side of the tilted ICM shortly after implantation. Asymmetric
      expression of Lefty1 can be established by in vitro culture, indicating that it
      does not require interaction with the uterus. The asymmetric Lefty1 expression is
      induced by Nodal signaling, although Nodal and genes for its effectors are
      expressed symmetrically. This asymmetry in molecular patterning of the mouse
      embryo pushes back the origin of the A-P body axis to the peri-implantation
      stage.

PMID- 16580992
TI  - Schnurri-2 controls BMP-dependent adipogenesis via interaction with Smad
      proteins.
AB  - Adipocyte differentiation is an important component of obesity, but how hormonal
      cues mediate adipocyte differentiation remains elusive. BMP stimulates in vitro
      adipocyte differentiation, but the role of BMP in adipogenesis in vivo is
      unknown. Drosophila Schnurri (Shn) is required for the signaling of
      Decapentaplegic, a Drosophila BMP homolog, via interaction with the Mad/Medea
      transcription factors. Vertebrates have three Shn orthologs, Shn-1, -2, and -3.
      Here, we report that Shn-2(-/-) mice have reduced white adipose tissue and that
      Shn-2(-/-) mouse embryonic fibroblasts cannot efficiently differentiate into
      adipocytes in vitro. Shn-2 enters the nucleus upon BMP-2 stimulation and, in
      cooperation with Smad1/4 and C/EBPalpha, induces the expression of PPARgamma2, a
      key transcription factor for adipocyte differentiation. Shn-2 directly interacts
      with both Smad1/4 and C/EBPalpha on the PPARgamma2 promoter. These results
      indicate that Shn-2-mediated BMP signaling has a critical role in adipogenesis.

PMID- 16580993
TI  - Analysis of cell migration using whole-genome expression profiling of migratory
      cells in the Drosophila ovary.
AB  - Cell migration contributes to normal development and homeostasis as well as to
      pathological processes such as inflammation and tumor metastasis. Previous
      genetic screens have revealed signaling pathways that govern follicle cell
      migrations in the Drosophila ovary, but few downstream targets of the critical
      transcriptional regulators have been identified. To characterize the gene
      expression profile of two migratory cell populations and identify Slbo targets,
      we purified border cells and centripetal cells expressing the mouse CD8 antigen
      and carried out whole-genome microarray analysis. Genes predicted to control
      actin dynamics and the endocytic and secretory pathways were overrepresented in
      the migratory cell transcriptome. Mutations in five genes, including ttk, failed
      to complement previously isolated mutations that cause cell migration defects in
      mosaic clones. Functional analysis revealed a role for the Notch-activating
      protease Kuzbanian in border cell migration and identified Tie as a guidance
      receptor for the border cells.

PMID- 16580994
TI  - Systematic analysis of the transcriptional switch inducing migration of border
      cells.
AB  - Cell migration within a natural context is tightly controlled, often by specific
      transcription factors. However, the switch from stationary to migratory behavior
      is poorly understood. Border cells perform a spatially and temporally controlled
      invasive migration during Drosophila oogenesis. Slbo, a C/EBP family
      transcriptional activator, is required for them to become migratory. We purified
      wild-type and slbo mutant border cells as well as nonmigratory follicle cells and
      performed comparative whole-genome expression profiling, followed by functional
      tests of the contributions of identified targets to migration. About 300 genes
      were significantly upregulated in border cells, many dependent on Slbo. Among
      these, the microtubule regulator Stathmin was strongly upregulated and was
      required for normal migration. Actin cytoskeleton regulators were also induced,
      including, surprisingly, a large cluster of "muscle-specific" genes. We conclude
      that Slbo induces multiple cytoskeletal effectors, and that each contributes to
      the behavioral changes in border cells.

PMID- 16580995
TI  - Two phases of astral microtubule activity during cytokinesis in C. elegans
      embryos.
AB  - Microtubules of the mitotic spindle are believed to provide positional cues for
      the assembly of the actin-based contractile ring and the formation of the
      subsequent cleavage furrow during cytokinesis. In Caenorhabditis elegans, astral
      microtubules have been thought to inhibit cortical contraction outside the
      cleavage furrow. Here, we demonstrate by live imaging and RNA interference (RNAi)
      that astral microtubules play two distinct roles in initiating cleavage furrow
      formation. In early anaphase, microtubules are required for contractile ring
      assembly; in late anaphase, microtubules show different cortical behavior and
      seem to suppress cortical contraction at the poles, as suggested in previous
      studies. These two distinct phases of microtubule behavior depend on distinct
      regulatory pathways, one involving the gamma-tubulin complex and the other
      requiring aurora-A kinase. We propose that temporal and spatial regulation of two
      distinct phases of astral microtubule behavior is crucial in specifying the
      position and timing of furrowing.

PMID- 16580996
TI  - Pachytene asynapsis drives meiotic sex chromosome inactivation and leads to
      substantial postmeiotic repression in spermatids.
AB  - Transcriptional silencing of the sex chromosomes during male meiosis (MSCI) is
      conserved among organisms with limited sex chromosome synapsis, including
      mammals. Since the 1990s the prevailing view has been that MSCI in mammals is
      transient, with sex chromosome reactivation occurring as cells exit meiosis.
      Recently, we found that any chromosome region unsynapsed during pachytene of male
      and female mouse meiosis is subject to transcriptional silencing (MSUC), and we
      hypothesized that MSCI is an inevitable consequence of this more general meiotic
      silencing mechanism. Here, we provide direct evidence that asynapsis does indeed
      drive MSCI. We also show that a substantial degree of transcriptional repression
      of the sex chromosomes is retained postmeiotically, and we provide evidence that
      this postmeiotic repression is a downstream consequence of MSCI/MSUC. While this
      postmeiotic repression occurs after the loss of MSUC-related proteins at the end
      of prophase, other histone modifications associated with transcriptional
      repression have by then become established.

PMID- 16580997
TI  - Genetic flexibility in the convergent evolution of hermaphroditism in
      Caenorhabditis nematodes.
AB  - The self-fertile hermaphrodites of C. elegans and C. briggsae evolved from female
      ancestors by acquiring limited spermatogenesis. Initiation of C. elegans
      hermaphrodite spermatogenesis requires germline translational repression of the
      female-promoting gene tra-2, which allows derepression of the three male
      promoting fem genes. Cessation of hermaphrodite spermatogenesis requires fem-3
      translational repression. We show that C. briggsae requires neither fem-2 nor fem
      3 for hermaphrodite development, and that XO Cb-fem-2/3 animals are transformed
      into hermaphrodites, not females as in C. elegans. Exhaustive screens for Cb-tra
      2 suppressors identified another 75 fem-like mutants, but all are self-fertile
      hermaphrodites rather than females. Control of hermaphrodite spermatogenesis
      therefore acts downstream of the fem genes in C. briggsae. The outwardly similar
      hermaphrodites of C. elegans and C. briggsae thus achieve self-fertility via
      intervention at different points in the core sex determination pathway. These
      findings are consistent with convergent evolution of hermaphroditism, which is
      marked by considerable developmental genetic flexibility.

PMID- 16580998
TI  - Role reversal: brain insulin and liver STAT3.
AB  - The central nervous system (CNS) actions of several hormones, including insulin,
      regulate metabolism in the liver and other peripheral tissues. Inoue et al.
      (2006) have now identified an IL-6/STAT3-dependent pathway in the liver that
      mediates a portion of the hepatic metabolic response to CNS insulin.

PMID- 16580999
TI  - Looking for food in all the right places?
AB  - Examining a potential functional role for growth hormone secretagogue receptors
      in the hippocampus, Diano and colleagues (Diano et al., 2006), demonstrate novel
      actions of the orexigenic peptide ghrelin in hippocampal synaptic architecture,
      LTP, and learning and memory. These data suggest functional links between
      metabolic signaling and higher neural function.

PMID- 16581000
TI  - Mapping out starvation responses.
AB  - What are the pathways that underlie the coordinated responses of an organism to
      well-fed and food-deprived states? A report in this issue of Cell Metabolism
      suggests that starvation functions via a muscarinic acetylcholine receptor to
      activate MAP kinase signaling in the pharyngeal muscle of C. elegans (You et al.,
      2006).

PMID- 16581001
TI  - Starvation activates MAP kinase through the muscarinic acetylcholine pathway in
      Caenorhabditis elegans pharynx.
AB  - Starvation activates MAPK in the pharyngeal muscles of C. elegans through a
      muscarinic acetylcholine receptor, Gqalpha, and nPKC as shown by the following
      results: (1) Starvation causes phosphorylation of MAPK in pharyngeal muscle. (2)
      In a sensitized genetic background in which Gqalpha signaling cannot be
      downregulated, activation of the pathway by a muscarinic agonist causes lethal
      changes in pharyngeal muscle function. Starvation has identical effects. (3) A
      muscarinic antagonist blocks the effects of starvation on sensitized muscle. (4)
      Mutations and drugs that block any step of signaling from the muscarinic receptor
      to MAPK also block the effects of starvation on sensitized muscle. (5)
      Overexpression of MAPK in wild-type pharyngeal muscle mimics the effects of
      muscarinic agonist and of starvation on sensitized muscle. We suggest that,
      during starvation, the muscarinic pathway to MAPK is activated to change the
      pharyngeal muscle physiology to enhance ingestion of food when food becomes
      available.

PMID- 16581002
TI  - Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE
      deficient mice against atherosclerosis.
AB  - Inflammatory processes play an important role in the pathogenesis of vascular
      diseases, and insulin-resistant diabetes mellitus type 2 represents an important
      risk factor for the development of atherosclerosis. To directly address the role
      of insulin resistance in myeloid lineage cells in the development of
      atherosclerosis, we have created mice with myeloid lineage-specific inactivation
      of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice
      developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS
      stimulated IL-6 and IL-1beta expression in the presence of macrophage autonomous
      insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on
      an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell
      transplantation of IRS-2(-/-) ApoE(-/-) cells ameliorated atherosclerosis in Apo
      E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin
      resistance has opposing effects on the development of atherosclerosis, providing
      direct evidence that myeloid lineage autonomous insulin signaling provides
      proinflammatory signals predisposing to the development of atherosclerosis.

PMID- 16581003
TI  - Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and
      necrotic core formation in advanced atherosclerotic lesions.
AB  - Insulin resistance in diabetes and metabolic syndrome is thought to increase
      susceptibility to atherosclerotic cardiovascular disease, but the underlying
      mechanisms are poorly understood. To evaluate the possibility that decreased
      insulin signaling in macrophage foam cells might worsen atherosclerosis, Ldlr(-/
      ) mice were transplanted with insulin receptor Insr(+/+) or Insr(-/-) bone
      marrow. Western diet-fed Insr(-/-) recipients developed larger, more complex
      lesions with increased necrotic cores and increased numbers of apoptotic cells.
      Insr(-/-) macrophages showed diminished Akt phosphorylation and an augmented ER
      stress response, leading to induction of scavenger receptor A and increased
      apoptosis when challenged with cholesterol loading or nutrient deprivation. These
      studies suggest that defective insulin signaling and reduced Akt activity impair
      the ability of macrophages to deal with ER stress-induced apoptosis within
      atherosclerotic plaques.

PMID- 16581004
TI  - Role of hepatic STAT3 in brain-insulin action on hepatic glucose production.
AB  - STAT3 regulates glucose homeostasis by suppressing the expression of
      gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is
      regulated by nutritional or hormonal status has remained unknown, however. Here,
      we show that an increase in the plasma insulin concentration, achieved either by
      glucose administration or by intravenous insulin infusion, stimulates tyrosine
      phosphorylation of STAT3 in the liver. This effect of insulin was mediated by the
      hormone's effects in the brain, and the increase in hepatic IL-6 induced by the
      brain-insulin action is essential for the activation of STAT3. The inhibition of
      hepatic glucose production and of expression of gluconeogenic genes induced by
      intracerebral ventricular insulin infusion was impaired in mice with liver
      specific STAT3 deficiency or in mice with IL-6 deficiency. These results thus
      indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in
      the brain, leading to the suppression of hepatic glucose production.

PMID- 16581005
TI  - Mitochondrial cytochrome oxidase produces nitric oxide under hypoxic conditions:
      implications for oxygen sensing and hypoxic signaling in eukaryotes.
AB  - Eukaryotic cells respond to low-oxygen concentrations by upregulating hypoxic
      nuclear genes (hypoxic signaling). Although it has been shown previously that the
      mitochondrial respiratory chain is required for hypoxic signaling, its underlying
      role in this process has been unclear. Here, we find that yeast and rat liver
      mitochondria produce nitric oxide (NO) at dissolved oxygen concentrations below
      20 microM. This NO production is nitrite (NO2-) dependent, requires an electron
      donor, and is carried out by cytochrome c oxidase in a pH-dependent fashion.
      Mitochondrial NO production in yeast is influenced by the YHb flavohemoglobin NO
      oxidoreductase, stimulates expression of the hypoxic nuclear gene CYC7, and is
      accompanied by an increase in protein tyrosine nitration. These findings
      demonstrate an alternative role for the mitochondrial respiratory chain under
      hypoxic or anoxic conditions and suggest that mitochondrially produced NO is
      involved in hypoxic signaling, possibly via a pathway that involves protein
      tyrosine nitration.

PMID- 16581007
TI  - Characterizing red light runners following implementation of a photo enforcement
      program.
AB  - Red light running causes about 260,000 crashes and 750 fatalities each year in
      the US (Retting, Ulmer, & Williams, 1999, Accident Analysis & Prevention). This
      study investigated the effects of photo enforcement cameras on reducing red light
      running and characterized the typical red light runner throughout photo
      enforcement program implementation. In Southeast Virginia, eight intersections
      were observed over an 8-month period during which photo enforcement cameras were
      installed at three sites. To assess spillover effects, three other sites served
      in a same city comparison group. Two additional sites from a nearby city served
      in a control group for city. Over 1750 light cycles were observed with red light
      running occurring at least once during 13% of these cycles. Predictors of red
      light runners included being at a site without a camera or at an intersection
      before deployment of cameras, being under the age of 26, being in the non-camera
      city, not using a safety belt, and driving in more traffic. While overall red
      light running decreased at camera sites, characteristics of the typical red light
      runner remained the same at camera and non-camera locations.

PMID- 16581008
TI  - Clay and oxide destabilization induced by mixed alum/macromolecular flocculation
      aids.
AB  - The review points out typical differences and analogies of the bulk
      characteristics of aluminum ion complexed polyelectrolytes and of their
      adsorption behaviors when such systems were supplied to inorganic colloids such
      as oxides and clays. It reports some particular investigations that were carried
      out in aqueous media to determine (i) the nature of the interactions existing
      between clay or oxides, aluminum ions and polyelectrolytes and (ii) the effects
      on the interfacial characteristics and the colloid stability related to the
      relative concentrations of these different constituents. The investigations
      concerned the synthetic alumina/polyacrylic acid systems and the natural
      kaolinite/humic acid systems, as well as partly the mixed alumina/humic acid
      systems. Different adsorption features and destabilization kinetics were
      determined to develop within these systems. One of the main constraints of the
      investigation arose from the presence of three interacting components which
      developed amphoteric and amphipatic interactions, the latter being generated by
      the hydrophobic moieties induced by the aluminum ions/carboxylic acid groups ion
      pairing. The investigations concerned the extent and the rate of transfer of
      hydrogen, aluminum ions and polyelectrolytes from the bulk solution to the solid
      surface. Electrical surface charge characteristics were expressed in terms of the
      zeta potential of the colloid/polymer complexes. The colloid stability of the
      systems was determined as a function of time at short and long terms. The
      variation as a function of time of the number and weight average masses was
      correlated with the variation with time of the zeta potential. All these systems
      were determined to reach the kinetic and thermodynamic equilibrium only slowly.
      Despite the fact that the supply of mixed coagulants provoked the initial
      aggregation and the subsequent fragmentation processes for both systems, the
      mechanisms responsible for the two processes were found to be different as
      revealed by comparatively investigating the synthetic and the natural systems.
      The fragmentation originated from the slow segregation process of positively and
      negatively charged groups for the natural kaolinite/humic acid systems, while the
      segregation process affected hydrophobic and hydrophilic moieties for the
      synthetic alumina/polyacrylic acid systems.

PMID- 16581006
TI  - Zebrafish fat-free is required for intestinal lipid absorption and Golgi
      apparatus structure.
AB  - The zebrafish fat-free (ffr) mutation was identified in a physiological screen
      for genes that regulate lipid metabolism. ffr mutant larvae are morphologically
      indistinguishable from wild-type sibling larvae, but their absorption of
      fluorescent lipids is severely impaired. Through positional cloning, we have
      identified a causative mutation in a highly conserved and ubiquitously expressed
      gene within the ffr locus. The Ffr protein contains a Dor-1 like domain typical
      of oligomeric Golgi complex (COG) gene, cog8. Golgi complex ultrastructure is
      disrupted in the ffr digestive tract. Consistent with a possible role in COG
      mediated Golgi function, wild-type Ffr-GFP and COG8-mRFP fusion proteins
      partially colocalize in zebrafish blastomeres. Enterocyte retention of an
      endosomal lipid marker in ffr larvae support the idea that altered vesicle
      trafficking contributes to the ffr mutant defect. These data indicate that ffr is
      required for both Golgi structure and vesicular trafficking, and ultimately lipid
      transport.

PMID- 16581009
TI  - Production of cis-syn thymine-thymine cyclobutane dimer oligonucleotide in the
      presence of acetone photosensitizer.
AB  - cis-syn Cyclobutane pyrimidine dimer (CPD) oligonucleotide was produced by UV
      irradiation in the presence of acetone photosensitizer. Acetone could enhance the
      productivity but evidently induced the photocleavage of oligonucleotide under a
      long time irradiation. A statistical approach of orthogonal design was applied to
      optimize the preparation condition for the production of the modified
      oligonucleotide. Optimal conditions for maximal cis-syn CPD oligonucleotide
      productivity were determined based on three factors: acetone concentration,
      initial oligonucleotide concentration, and irradiation time at several different
      levels. The optimal modified oligonucleotide that this optimization could produce
      was 32.7%. Through analysis of 20% polyacrylamide gel electrophoresis, it was
      found that modified oligonucleotide migrated slightly more slowly than the parent
      oligonucleotide. The photoreactivation of cis-syn thymine-thymine dimer
      oligonucleotide displayed the selectivity of the substrate specificity of DNA
      photolyase with high-performance liquid chromatography (HPLC) analysis.

PMID- 16581010
TI  - Positively charged peptides can interact with each other, as revealed by solid
      phase binding assays.
AB  - Solid phase assay systems such as enzyme-linked immunosorbent assay (ELISA),
      surface plasmon resonance (SPR), and overlay gels are used to study processes of
      protein-protein interactions. The common principle of all these methods is that
      they monitor the binding between soluble and surface-immobilized molecules.
      Following the use of bovine serum albumin (BSA)-peptide conjugates or isolated
      synthetic peptides and the above-mentioned solid phase assay systems, the results
      of the current work demonstrate that positively charged peptides can interact
      with each other. Both the ELISA and SPR methods demonstrated that the binding
      process reached saturation with K(d) values ranging between 1 and 14 nM. No
      interaction was observed between BSA conjugates bearing positively charged
      peptides and conjugates bearing negatively charged peptides or with pure BSA
      molecules, strengthening the view that interaction occurs only between positively
      charged peptides. However, interactions between peptides in solution were not
      observed by nuclear magnetic resonance (NMR) or by native gel electrophoresis. It
      appears that for positively charged molecules to interact, one of the binding
      partners must be immobilized to a surface, a process that may lead to the
      exposure of otherwise masked groups or atoms. We discuss the relevance of our
      findings for the use of solid phase assay systems to study interactions between
      biomolecules.

PMID- 16581011
TI  - Preparation of UDP-galacturonic acid using UDP-sugar pyrophosphorylase.
AB  - UDP-galacturonic acid, the activated form of galacturonic acid (GalUA), is
      synthesized both de novo and by salvage pathways. The UDP-GalUA pyrophosphorylase
      gene involved in the salvage pathway has not been identified. Here we show that
      UDP-sugar pyrophosphorylase from Pisum sativum with a broad specificity has UDP
      GalUA pyrophosphorylase activity. The enzyme catalyzed the formation of UDP-GalUA
      and pyrophosphate from GalUA 1-phosphate and UTP with an equilibrium constant
      value of 0.24. The recombinant UDP-sugar pyrophosphorylase had optimal pH of 6.0,
      and the apparent K(m) values for GalUA 1-phosphate, UTP, UDP-GalUA, and
      pyrophosphate were 2.27, 1.15, 0.70, and 1.26 mM, respectively. In the presence
      of inorganic pyrophosphatase, the recombinant enzyme produced UDP-GalUA in an 84%
      yield (based on the GalUA 1-phosphate substrate) on a preparative scale. Thus,
      this UDP-sugar pyrophosphorylase is useful for the highly efficient production of
      UDP-GalUA for studies on pectin biosynthesis.

PMID- 16581012
TI  - Quercetin-dependent scavenging of reactive nitrogen species derived from nitric
      oxide and nitrite in the human oral cavity: interaction of quercetin with
      salivary redox components.
AB  - In the human oral cavity, nitrite is reduced to nitric oxide (NO) by certain
      bacteria. The NO formed reacts with O2 to generate NO2 and then with NO2
      producing N2O3. In this study, N2O3 produced by the reaction between NO and NO2
      was detected by fluorescence increase due to the transformation of 4,5
      diaminofluorescein to fluorescent triazolfluorescein. Nitrite-induced
      fluorescence increase in the bacterial fraction of saliva was completely
      inhibited by 1muM quercetin and the complete inhibition continued until almost
      all quercetin had been oxidized. Nitrite-induced fluorescence increase was also
      observed in the saliva which contained salivary redox components. Quercetin
      effectively inhibited the fluorescence increase. During the inhibition of the
      fluorescence increases by quercetin, the flavonol was oxidized. NO2 seemed to
      participate in the oxidation. The main oxidation product was 2-(3,4
      dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofurane. Thiocyanate inhibited the
      fluorescence increase in bacterial fraction and duration of the complete
      inhibition by quercetin was prolonged by SCN-. The inhibition and the
      prolongation are discussed to be due to SCN--dependent inhibition of oxidation of
      nitrite to NO2 by salivary peroxidase. Quercetin cooperated with ascorbate to
      inhibit the fluorescence increase. From the results obtained in this study, it is
      deduced (1) that quercetin can protect human oral cavity from damages induced by
      reactive nitrogen species and (2) that the protective function of quercetin may
      be significant when antioxidant capacity of saliva is decreased by periodontal
      diseases.

PMID- 16581013
TI  - A functionally inactive, cold-stabilized form of the Escherichia coli F1Fo ATP
      synthase.
AB  - An unusual effect of temperature on the ATPase activity of E. coli F1Fo ATP
      synthase has been investigated. The rate of ATP hydrolysis by the isolated
      enzyme, previously kept on ice, showed a lag phase when measured at 15 degrees C,
      but not at 37 degrees C. A pre-incubation of the enzyme at room temperature for 5
      min completely eliminated the lag phase, and resulted in a higher steady-state
      rate. Similar results were obtained using the isolated enzyme after incorporation
      into liposomes. The initial rates of ATP-dependent proton translocation, as
      measured by 9-amino-6-chloro-2-methoxyacridine (ACMA) fluorescence quenching, at
      15 degrees C also varied according to the pre-incubation temperature. The
      relationship between this temperature-dependent pattern of enzyme activity,
      termed thermohysteresis, and pre-incubation with other agents was examined. Pre
      incubation of membrane vesicles with azide and Mg2+, without exogenous ADP,
      resulted in almost complete inhibition of the initial rate of ATPase when assayed
      at 10 degrees C, but had little effect at 37 degrees C. Rates of ATP synthesis
      following this pre-incubation were not affected at any temperature. Azide
      inhibition of ATP hydrolysis by the isolated enzyme was reduced when an ATP
      regenerating system was used. A gradual reactivation of azide-blocked enzyme was
      slowed down by the presence of phosphate in the reaction medium. The well-known
      Mg2+ inhibition of ATP hydrolysis was shown to be greatly enhanced at 15 degrees
      C relative to at 37 degrees C. The results suggest that thermohysteresis is a
      consequence of an inactive form of the enzyme that is stabilized by the binding
      of inhibitory Mg-ADP.

PMID- 16581015
TI  - The mechanism of proton transfer between adjacent sites on the molecular surface.
AB  - The surface of a protein, or a membrane, is spotted with a multitude of proton
      binding sites, some of which are only few A apart. When a proton is released from
      one site, it propagates through the water by a random walk under the bias of the
      local electrostatic potential determined by the distribution of the charges on
      the protein. Eventually, the released protons are dispersed in the bulk, but
      during the first few nanoseconds after the dissociation, the protons can be
      trapped by encounter with nearby acceptor sites. While the study of this reaction
      on the surface of a protein suffers from experimental and theoretical
      difficulties, it can be investigated with simple model compounds like derivatives
      of fluorescein. In the present study, we evaluate the mechanism of proton
      transfer reactions that proceed, preferentially, inside the Coulomb cage of the
      dye molecules. Kinetic analysis of the measured dynamics reveals the role of the
      dimension of the Coulomb cage on the efficiency of the reaction and how the
      ordering of the water molecules by the dye affects the kinetic isotope effect.

PMID- 16581014
TI  - Possibility of transkingdom gene therapy for complex I diseases.
AB  - Defects of complex I are involved in many human mitochondrial diseases, and
      therefore we have proposed to use the NDI1 gene encoding a single subunit NADH
      dehydrogenase of Saccharomyces cerevisiae for repair of respiratory activity. The
      yeast NDI1 gene was successfully introduced into mammalian cell lines. The
      expressed NDI1 protein was correctly targeted to the matrix side of the inner
      mitochondrial membranes, was fully functional and restored the NADH oxidase
      activity to the complex I-deficient cells. The NDI1-transduced cells were more
      resistant to complex I inhibitors and diminished production of reactive oxygen
      species induced by rotenone. It was further shown that the NDI1 protein can be
      functionally expressed in tissues such as skeletal muscles and the brain of
      rodents, which scarcely induced an inflammatory response. The use of NDI1 as a
      potential molecular therapy for complex I-deficient diseases is briefly
      discussed, including the proposed animal model.

PMID- 16581016
TI  - Aquaporin-1 in the peritoneal membrane: Implications for water transport across
      capillaries and peritoneal dialysis.
AB  - Peritoneal dialysis (PD) is an established mode of renal replacement therapy,
      based on the exchange of fluid and solutes between blood in peritoneal
      capillaries and a dialysate that has been introduced in the peritoneal cavity.
      The dialysis involves diffusive and convective transports and osmosis through the
      highly vascularized peritoneal membrane. Computer simulations predicted that the
      membrane contains ultrasmall pores (radius < 3 A) responsible for the transport
      of solute-free water across the capillary endothelium during crystalloid osmosis.
      The distribution of the water channel aquaporin-1 (AQP1), as well as its
      molecular structure ensuring an exquisite selectivity for water perfectly fit
      with the characteristics of the ultrasmall pore. Treatment with corticosteroids
      induces the expression of AQP1 in peritoneal capillaries and increases water
      permeability and ultrafiltration in rats, without affecting the osmotic gradient
      and the permeability for small solutes. Studies in knockout mice provided further
      evidence that osmotically-driven water transport across the peritoneal membrane
      is mediated by AQP1. AQP1 and endothelial NO synthase (eNOS) show a distinct
      regulation within the endothelium lining peritoneal capillaries. In acute
      peritonitis, the upregulation of eNOS and increased release of NO dissipate the
      osmotic gradient and result in ultrafiltration failure, despite the unchanged
      expression of AQP1. These data illustrate the potential of the peritoneal
      membrane to investigate the role and regulation of AQP1 in the endothelium. They
      also emphasize the critical role of AQP1 during peritoneal dialysis and suggest
      that manipulating AQP1 expression may be used to increase water permeability
      across the peritoneal membrane.

PMID- 16581017
TI  - Y55 and D78 are crucial amino acid residues of a new IgE epitope on
      trichosanthin.
AB  - Trichosanthin (TCS) possesses many biological and pharmaceutical activities, but
      its strong immunogenicity limits its clinical application. To reduce the
      immunogenicity of TCS, we modified the reported method for the prediction of
      antigenic site and identified two crucial amino acid residues (Y55 and D78) for a
      new epitope. We mutated these two residues into glycine and serine, respectively,
      and obtained three mutants, Y55G, D78S, and Y55G/D78S. These mutants induced less
      amount of Ig and IgG antibodies in C57BL/6J mice than wild-type TCS (wTCS)
      (p<0.01) and almost lost the ability to induce IgE antibody production. The
      mutants stimulated fewer TCS-specific B cells in C57BL/6J mice than wTCS
      (p<0.01). Compared with wTCS, Y55G, D78S, and Y55G/D78S lost 26.9%, 17.9%, and
      98.7% specific binding ability to anti-TCS monoclonal antibody TCS4E9,
      respectively. These mutants still retained RNA N-glycosidase activity. In
      conclusion, Y55 and D78 are two crucial amino acid residues of a new IgE epitope
      on TCS, and their mutation reduces the immunogenicity of TCS, but still retained
      the enzymatic activity.

PMID- 16581018
TI  - CpG islands are the second main factor shaping codon usage in human genes.
AB  - A correspondence analysis of codon usage in human genes revealed, as expected,
      that the first axis is strongly correlated with the base composition at
      synonymous third codon positions. At one extreme of the second axis were
      localized genes with a high frequency of NCG and CGN codons. The great majority
      of these sequences were embedded in CpG islands, while the opposite is true for
      the genes placed at the other extreme. The two main conclusions of this paper
      are: (1) the influence of CpG islands on codon usage, and (2) since the second
      axis is orthogonal (and therefore independent) of the first, GC3-rich genes are
      not necessarily associated with CpG islands.

PMID- 16581019
TI  - Downregulation of KCC2 following LTP contributes to EPSP-spike potentiation in
      rat hippocampus.
AB  - GABAergic synaptic inhibition plays a critical role in regulating long-term
      potentiation (LTP) of glutamatergic synaptic transmission and circuit output. The
      K(+)-Cl(-) cotransporter 2 (KCC2) is an important factor in determining
      inhibitory GABAergic synaptic strength besides the contribution of GABA(A)
      receptor. Although much knowledge has been gained regarding activity-dependent
      downregulation of KCC2 in many pathological conditions, the potential change and
      contribution of KCC2 in LTP expression is still unknown. In this study, we found
      that downregulation of KCC2 was accompanied with the occurrence of LTP but not
      that of long-term depression in hippocampal CA1 region. Meanwhile, KCC2 level in
      CA3/DG and adjacent cortex was stable in the process of LTP expression in
      Schaffer collateral synapses. Blockade of NMDA receptor with APV not only
      prevented LTP induction also abolished the reduction of KCC2. Furthermore, the
      inhibition of KCC2 function with furosemide directly induced EPSP-spike (E-S)
      potentiation, an important component of LTP in hippocampus. The present data
      suggest a novel mechanism that LTP formation is accompanied by the downregulation
      of KCC2, which is underlying GABAergic strength and most likely contributes to
      the E-S potentiation following LTP.

PMID- 16581020
TI  - Calcium signaling and sugar-induced activation of plasma membrane H(+)-ATPase in
      Saccharomyces cerevisiae cells.
AB  - In this work, we show that glucose-induced activation of plasma membrane H(+)
      ATPase from Saccharomyces cerevisiae is strongly dependent on calcium metabolism
      and that the glucose sensor Snf3p works in a parallel way with the G protein
      Gpa2p in the control of the pathway. The role of Snf3p is played by the Snf3p C
      terminal tail, since in a strain with the deletion of the SNF3 gene, but also
      expressing a chimera protein formed by Hxt1p (a glucose transporter) and the
      Snf3p C-terminal tail, a normal glucose-activation process can be observed. We
      present evidences indicating that Snf3p would be the sensor for the internal
      signal (phosphorylated sugars) of this pathway that would connect calcium
      signaling and activation of the plasma membrane ATPase. We also show that Snf3p
      could be involved in the control of Pmc1p activity that would regulate the
      calcium availability in the cytosol.

PMID- 16581021
TI  - Frequency-dependent modulation of KCNQ1 and HERG1 potassium channels.
AB  - To obtain information about a possible frequency-dependent modulation of HERG1
      and hKCNQ1 channels, we performed heterologous expression in Xenopus laevis
      oocytes. Channel activation was obtained by voltage protocols roughly imitating
      cardiac action potentials at frequencies of 1, 3, 5.8, and 8.3Hz. The activity of
      HERG1 channels was inhibited down to 65% at high frequencies. In contrast, hKCNQ1
      channel activity was increased up to 525% at high frequencies. The general
      frequency-dependent modulation of the channels was unaffected by both co
      expression of hKCNQ1 and HERG1 channels, and by the presence of the beta-subunits
      KCNE1 and KCNE2. In addition, the functional role of HERG1 in native guinea pig
      cardiac myocytes was demonstrated at different pacing frequencies by application
      of 10microM of the new HERG1 activator, NS1643. In conclusion, we have
      demonstrated that HERG1 and hKCNQ1 channels are inversely modulated by
      stimulation frequency.

PMID- 16581022
TI  - Truncated form of VACM-1/cul-5 with an extended 3' untranslated region stimulates
      cell growth via a MAPK-dependent pathway.
AB  - We have sequenced a 4.9kb clone (KLB22) which shares 99% sequence homology with
      the rabbit vasopressin-activated calcium mobilizing (VACM-1) protein. The 5'
      terminus sequence of KLB22 cDNA (nucleotides 1-1961) is continuous and
      overlapping with nucleotides 1226-3186 of the VACM-1 cDNA sequence. The 3'UTR of
      KLB22 cDNA extends beyond the 3'UTR of VACM-1 by 2999nt. KLB22 cDNA encodes a 497
      amino acid protein, which putatively begins at Met 284 of the 780 amino acid VACM
      1 protein. The in vitro translation of KLB22 cDNA yields a 59kDa protein. When
      expressed in cos-1 cells, the truncated VACM-1 protein localizes to the nucleus.
      KLB22 cDNA transfected cells show increased growth rates and increased levels of
      phosphorylated MAPK when compared to the vector or to VACM-1 cDNA transfected
      cells. Finally, in vivo, KLB22 protein expression is tissue specific and can be
      detected in kidney and in heart atrium. These results suggest that truncated VACM
      1 cDNA (KLB22) increases cell proliferation through a MAPK pathway.

PMID- 16581023
TI  - Leucine-induced activation of translational initiation is partly regulated by the
      branched-chain alpha-keto acid dehydrogenase complex in C2C12 cells.
AB  - Branched-chain amino acid leucine has been shown to activate the translational
      regulators through the mammalian target of rapamycin. However, the leucine's
      effects are self-limiting because leucine promotes its own disposal by an
      oxidative pathway. The irreversible and rate-limiting step in the leucine
      oxidation pathway is catalyzed by the branched-chain alpha-keto acid
      dehydrogenase (BCKDH) complex. The complex contains E1 (alpha2beta2), E2, and E3
      subunits, and its activity is abolished by phosphorylation of the E1alpha subunit
      by BCKDH kinase. The relationship between the activity of BCKDH complex and
      leucine-mediated activation of the protein translation was investigated using the
      technique of RNA interference. The activity of BCKDH complex in C2C12 cell was
      modulated by transfection of small interfering RNA (siRNA) for BCKDH E2 subunit
      or BCKDH kinase. Transfection of siRNAs decreased the mRNA expression and protein
      amount of corresponding gene. Suppression of either E2 subunit or kinase produced
      opposite effects on the cell proliferation and the activation of translational
      regulators by leucine. Suppression of BCKDH kinase for 48h resulted in decreasing
      cell proliferation. In contrast, E2 suppression led to increased amount of total
      cellular protein. The phosphorylation of p70 S6 kinase by leucine was increased
      in E2-siRNA transfected C2C12 cells, whereas the leucine's effect was diminished
      in kinase-siRNA transfected cells. These results suggest that the activation of
      the translational regulators by leucine was partly regulated by the activity of
      BCKDH complex.

PMID- 16581024
TI  - Interaction-based evaluation of the propensity for amyloid formation with cross
      beta structure.
AB  - In order to reveal the requirements for amino acid sequences prone to form
      amyloid fibrils, a novel prediction method based on the original structural model
      of amyloids was developed. As a working hypothesis, two fundamental conditions
      were introduced into the design of the present system for the evaluation of the
      propensity for amyloidogenicity. The first of these two conditions was to ensure
      that the hydrophobic and hydrogen-bonding interactions between residues on
      neighboring antiparallel beta-strands were formed along a fibril axis. The other
      condition was that the hydrophobic interacting residues appeared on both faces of
      the protofibril, which gave line-matching interactions. Most peptides with
      sequences exhibiting high scores, as evaluated by this method, were found to
      easily form amyloids with the aid of a turn-inducing structure designed as a
      connection of two beta-strands. On the other hand, peptides with low-scoring
      native sequences and those modified by an internal residue-residue exchange (the
      latter yielding a null score) did not lead to amyloid formation. These data
      demonstrated the validity of this method for the prediction of amyloid
      structures. Moreover, the present study provided support for the proposed model
      of the essential structure associated with the above working hypothesis. The
      predicted high-scoring regions were in good agreement with the putative amyloid
      core regions reported thus far.

PMID- 16581025
TI  - Trimeric structure of the wild soluble chloride intracellular ion channel CLIC4
      observed in crystals.
AB  - The crystal structure of a wild type of the human soluble chloride intracellular
      ion channel CLIC4 (wCLIC4) has been determined at a resolution of 2.2A. The
      structure shows a homotrimer in an asymmetric unit, which is first observed in
      CLICs. The assembly of the trimer takes a unique triple interaction mode between
      three monomers with a hydrogen-bond network and hydrophobic contacts. Through
      such complicated interactions, the homotrimer of wCLIC4 is firmly stabilized. The
      structure shows an oligomeric mode with a unique assembly mechanism by which the
      oligomerization of CLIC4 can be performed without any intramolecular disulfide
      bond formation. It indicated a possibility that CLIC4 may take a unique
      structural organization distinct from CLIC1 for docking with lipid bilayers. In
      addition, the structure shows distinct conformational states of the h2 region for
      respective monomers of the trimer, which reveal an intrinsic conformational
      susceptibility for this significant region in the structural transition.

PMID- 16581026
TI  - Epithelial sodium channel is regulated by SNAP-23/syntaxin 1A interplay.
AB  - Sodium-selective amiloride-sensitive epithelial channel (ENaC) located in the
      apical membrane is involved in the reabsorption of sodium in tight epithelia. The
      soluble N-ethylmaleimide-sensitive attachment receptors (SNAREs) mediate vesicle
      trafficking in a variety of cell systems. Syntaxin (a t-SNARE) has been shown to
      interact with and functionally regulate a number of ion channels including ENaC.
      In this study, we investigated the role of SNAP-23, another SNARE protein, on
      ENaC activity in the HT-29 colonic epithelial cell system and Xenopus oocytes.
      Recording of amiloride-sensitive currents in both systems suggest that SNAP-23
      modulates channel function, though a much higher concentration is required to
      inhibit ENaC in Xenopus oocytes. The introduction of Botulinum toxin A (a
      neurotoxin which cleaves SNAP-23), but not Botulinum toxin B or heat-inactivated
      Botulinum toxin A, reversed the inhibitory effect of SNAP-23 on amiloride
      sensitive currents. However, syntaxin 1A and SNAP-23 combined portray a complex
      scenario that suggests that this channel interacts within a quaternary complex.
      Synaptotagmin expression neither interacts with, nor showed any effect on
      amiloride-sensitive currents when co-expressed with ENaC. Pull down assays
      suggest mild interaction between ENaC and SNAP-23, which gets stronger in the
      presence of syntaxin 1A. Data further suggest that SNAP-23 possibly interacts
      with the N-terminal alphaENaC. These functional and biochemical approaches
      provide evidence for a complex relationship between ENaC and the exocytotic
      machinery. Our data suggest that SNARE protein interplay defines the fine
      regulation of sodium channel function.

PMID- 16581028
TI  - Identification of a nuclear localization signal in the retinitis pigmentosa
      mutated RP26 protein, ceramide kinase-like protein.
AB  - Retinitis pigmentosa (RP) is a genetically heterogeneous disease characterized by
      degeneration of the retina. A mutation in a new ceramide kinase (CERK) homologous
      gene, named CERK-like protein (CERKL), was found to cause autosomal recessive
      retinitis pigmentosa (RP26). Here, we show a point mutation of one of two
      putative nuclear localization signal (NLS) sequences inhibited the nuclear
      localization of the protein. Furthermore, the tetra-GFP-tagged NLS, which cannot
      passively enter the nucleus, was observed not only in the nucleus but also in the
      nucleolus. Our results provide the first evidence of the active nuclear import of
      CERKL and suggest that the identified NLS might be responsible for nucleolar
      retention of the protein. As recent studies have shown other RP-related proteins
      are localized in the nucleus or the nucleolus, our identification of NLS in CERKL
      suggests that CERKL likely plays important roles for retinal functions in the
      nucleus and the nucleolus.

PMID- 16581027
TI  - Suppression of receptor-mediated apoptosis by death effecter domain recruiting
      domain binding peptide aptamer.
AB  - FLASH protein is a component of death-inducing signaling complex and might be
      involved in death receptor-mediated extrinsic apoptosis. Here we developed the
      peptide aptamer against death effecter domain recruiting domain (DRD) of FLASH
      protein and showed that the peptide bound to FLASH protein in vitro.
      Intracellular expression of the DRD-binding peptide aptamer specifically
      suppressed receptor-mediated extrinsic apoptosis but not intrinsic pathway, which
      was recapitulated by the antisense oligonucleotides for FLASH. These data suggest
      that DRD-binding peptide is not only a novel inhibitor modulating receptor
      mediated apoptosis but also a tool for elucidating the roles of FLASH in
      apoptosis.

PMID- 16581029
TI  - Evaluation of dichloroacetate treatment in a murine model of hereditary
      tyrosinemia type 1.
AB  - Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disease severely
      affecting liver and kidney and is caused by a deficiency in fumarylacetoacetate
      hydrolase (FAH). Administration of 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3
      cyclohexanedione (NTBC) improves the HT1 phenotype but some patients do not
      respond to NTBC therapy. The objective of the present study was to evaluate
      whether administration of dichloroacetate, an inhibitor of maleyl acetoacetate
      isomerase (MAAI) to FAH-knockout mice could prevent acute pathological injury
      caused by NTBC withdrawal. DCA (0.5 and 5g/L) was given in combination with a
      standard diet or with a tyrosine-restricted diet. With the low-tyrosine diet body
      weight loss and most of hepatic and renal injuries were prevented regardless the
      DCA dose. The administration of DCA with a standard diet did not prevent damage
      nor the oxidative stress response nor the AFP induction seen in FAH-knockout
      mice. DCA was shown to inhibit hepatic MAAI activity to 86% (0.5g/L) and 94%
      (5g/L) of untreated wild-type mice. Interestingly, FAH(-/-) mice deprived of NTBC
      (NTBC-OFF) and NTBC-treated FAH-knockout mice had similar low hepatic MAAI
      activity levels, corresponding to 10-20% of control. Thus the failure of DCA
      treatment in FAH(-/-) mice seems to be attributed to the residual MAAI activity,
      high enough to lead to FAA accumulation and HT1 phenotype.

PMID- 16581030
TI  - G72/G30 in schizophrenia and bipolar disorder: review and meta-analysis.
AB  - Association of the G72/G30 locus with schizophrenia and bipolar disorder has now
      been reported in several studies. The G72/G30 locus may be one of several that
      account for the evidence of linkage that spans a broad region of chromosome 13q.
      However, the story of G72/G30 is complex. Our meta-analysis of published
      association studies shows highly significant evidence of association between
      nucleotide variations in the G72/G30 region and schizophrenia, along with
      compelling evidence of association with bipolar disorder. But the associated
      alleles and haplotypes are not identical across studies, and some strongly
      associated variants are located approximately 50 kb telomeric of G72.
      Interestingly, G72 and G30 are transcribed in opposite directions; hence, their
      transcripts could cross-regulate translation. A functional native protein and
      functional motifs for G72 or G30 remain to be demonstrated. The interaction of
      G72 with d-amino acid oxidase, itself of interest as a modulator of N-methyl-d
      aspartate receptors through regulation of d-serine levels, has been reported in
      one study and could be a key functional link that deserves further investigation.
      The association findings in the G72/G30 region, among the most compelling in
      psychiatry, may expose an important molecular pathway involved in susceptibility
      to schizophrenia and bipolar disorder.

PMID- 16581032
TI  - Imaging in Parkinson's disease: the role of monoamines in behavior.
AB  - Positron emission tomography (PET) and single photon emission computed tomography
      (SPECT) can measure striatal dopamine (DA) terminal function in vivo as reflected
      by DA storage capacity and transporter binding. In Parkinson's disease (PD)
      posterior dorsal putamen DA terminals are initially targeted, the anterior
      putamen and head of caudate subsequently becoming affected. In contrast,
      dopaminergic function in pallidal, amygdala, and cingulate regions is upregulated
      in early PD and only later becomes reduced. Rigidity and bradykinesia in PD have
      been shown to correlate with loss of putamen dopaminergic function, whereas
      performance on executive and working memory tasks correlates with integrity of
      caudate dopaminergic terminals. 11C-RTI32 PET, a marker of noradrenergic and
      dopaminergic transporter binding, can be used to assess noradrenergic along with
      dopaminergic terminal function. Serotonergic transporter binding can be assessed
      with 11C-DASB PET and 123I-beta CIT SPECT, whereas HT1A binding can be measured
      with 11C-WAY100635 PET. With these modalities, the relationship between mood,
      noradrenergic and serotonergic function can be examined in PD. The functional
      effects of focal DA replacement on DA storage capacity and patterns of brain
      activation via implantation of fetal midbrain cells or glial derived neurotrophic
      factor (GDNF) infusion into putamen of PD patients has been examined with PET.
      Both approaches lead to consistently increased levels of putamen 18F-dopa uptake,
      and cell implantation can restore levels of frontal activation. Clinical outcome,
      however, has proved to be variable and off-medication dyskinesias are an unwanted
      side effect in transplanted cases. Dopamine release after pharmacological
      challenges or during behavioral tasks can be assessed indirectly by studying
      changes in receptor availability to PET radioligands. Stereotyped sequential
      movements are associated with striatal DA release, and this increases with more
      complex behaviors and the presence of financial incentives, which also increase
      frontal DA levels. Parkinson patients release less putamen DA than healthy
      control subjects during stereotyped finger movements. Interestingly, those PD
      patients who develop a dopa dependency syndrome, craving their medication,
      generate significantly greater levels of ventral striatal DA compared with
      similarly disabled patients without such a psychological dependency. In the
      future, functional imaging is likely to throw light on the roles of peptide
      transmission in regulating mood and behavior as non-peptide analogue ligands
      become available. Novel markers of amyloid plaque load will also help clarify the
      etiology of dementia in PD.

PMID- 16581031
TI  - A neurobehavioral systems analysis of adult rats exposed to methylazoxymethanol
      acetate on E17: implications for the neuropathology of schizophrenia.
AB  - BACKGROUND: As a test of plausibility for the hypothesis that schizophrenia can
      result from abnormal brain, especially cerebral cortical, development, these
      studies examined whether, in the rat, disruption of brain development initiated
      on embryonic day (E) 17, using the methylating agent methylazoxymethanol acetate
      (MAM), leads to a schizophrenia-relevant pattern of neural and behavioral
      pathology. Specifically, we tested whether this manipulation leads to disruptions
      of frontal and limbic corticostriatal circuit function, while producing
      schizophrenia-like, region-dependent reductions in gray matter in cortex and
      thalamus. METHODS: In offspring of rats administered MAM (22 mg/kg) on E17 or
      earlier (E15), regional size, neuron number and neuron density were determined in
      multiple brain regions. Spontaneous synaptic activity at prefrontal cortical
      (PFC) and ventral striatal (vSTR) neurons was recorded in vivio. Finally,
      cognitive and sensorimotor processes mediated by frontal and limbic
      corticostriatal circuits were assessed. RESULTS: Adult MAM-E17-exposed offspring
      showed selective histopathology: size reductions in mediodorsal thalamus,
      hippocampus, and parahippocampal, prefrontal, and occipital cortices, but not in
      sensory midbrain, cerebellum, or sensorimotor cortex. The prefrontal, perirhinal,
      and occipital cortices showed increased neuron density with no neuron loss. The
      histopathology was accompanied by a disruption of synaptically-driven "bistable
      membrane states" in PFC and vSTR neurons, and, at the behavioral level, cognitive
      inflexibility, orofacial dyskinesias, sensorimotor gating deficits and a post
      pubertal-emerging hyper-responsiveness to amphetamine. Earlier embryonic MAM
      exposure led to microcephaly and a motor phenotype. CONCLUSIONS: The "MAM-E17"
      rodent models key aspects of neuropathology in circuits that are highly relevant
      to schizophrenia.

PMID- 16581033
TI  - Telomere shortening and mood disorders: preliminary support for a chronic stress
      model of accelerated aging.
AB  - BACKGROUND: Little is known about the biological mechanisms underlying the excess
      medical morbidity and mortality associated with mood disorders. Substantial
      evidence supports abnormalities in stress-related biological systems in
      depression. Accelerated telomere shortening may reflect stress-related oxidative
      damage to cells and accelerated aging, and severe psychosocial stress has been
      linked to telomere shortening. We propose that chronic stress associated with
      mood disorders may contribute to excess vulnerability for diseases of aging such
      as cardiovascular disease and possibly some cancers through accelerated
      organismal aging. METHODS: Telomere length was measured by Southern Analysis in
      44 individuals with chronic mood disorders and 44 nonpsychiatrically ill age
      matched control subjects. RESULTS: Telomere length was significantly shorter in
      those with mood disorders, representing as much as 10 years of accelerated aging.
      CONCLUSIONS: These results provide preliminary evidence that mood disorders are
      associated with accelerated aging and may suggest a novel mechanism for mood
      disorder-associated morbidity and mortality.

PMID- 16581034
TI  - Tic symptom profiles in subjects with Tourette Syndrome from two genetically
      isolated populations.
AB  - BACKGROUND: Tourette Syndrome (TS) has a complex etiology and wide variability in
      phenotypic expression. Identifying underlying symptom patterns may be useful for
      etiological and outcome studies of TS. METHODS: Lifetime tic and related symptom
      data were collected between 1996 and 2001 in 121 TS subjects from the Central
      Valley of Costa Rica and 133 TS subjects from the Ashkenazi Jewish (AS)
      population in the US. Subjects were grouped by tic symptoms using an
      agglomerative hierarchical cluster analysis. Cluster membership was tested for
      association with available ancillary information (age of onset, tic severity,
      comorbid disorders, medication treatment and family history). RESULTS: Cluster
      analysis identified two distinct groups in each sample, those with predominantly
      simple tics (cluster 1), and those with multiple complex tics (cluster 2).
      Membership in cluster 2 was correlated with increased tic severity, global
      impairment, medication treatment, and presence of comorbid obsessive-compulsive
      symptoms in both samples, and with family history of tics, lower verbal IQ,
      earlier age of onset, and comorbid obsessive-compulsive disorder and attention
      deficit/hyperactivity disorder in the AS sample. CONCLUSIONS: This study provides
      evidence for consistent and reproducible symptom profiles in two independent TS
      study samples. These findings have implications for etiological studies of TS.

PMID- 16581035
TI  - No human tryptophan hydroxylase-2 gene R441H mutation in a large cohort of
      psychiatric patients and control subjects.
AB  - BACKGROUND: It was recently reported that a rare functional variant, R441H, in
      the human tryptophan hydroxylase-2 gene (hTPH2) could represent an important risk
      factor for unipolar major depression (UP) since it was originally found in 10% of
      UP patients (vs. 1.4% in control subjects). METHODS: We explored the occurrence
      of this variation in patients with affective disorders (n = 646), autism spectrum
      disorders (n = 224), and obsessive-compulsive disorder (OCD) (n = 201); in
      healthy volunteers with no psychiatric disorders (n = 246); and in an ethnic
      panel of control individuals from North Africa, Sub-Saharan Africa, India, China,
      and Sweden (n = 277). RESULTS: Surprisingly, we did not observe the R441H variant
      in any of the individuals screened (3188 independent chromosomes). CONCLUSIONS:
      Our results do not confirm the role of the R441H mutation of the hTPH2 gene in
      the susceptibility to UP. The absence of the variant from a large cohort of
      psychiatric patients and control subjects suggests that the findings reported in
      the original study could be due to a genotyping error or to stratification of the
      initial population reported. Additional data by other groups should contribute to
      the clarification of the discrepancy between our results and those previous
      published.

PMID- 16581036
TI  - Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting
      with major depressive disorder.
AB  - BACKGROUND: Insomnia and major depressive disorder (MDD) can coexist. This study
      evaluated the effect of adding eszopiclone to fluoxetine. METHODS: Patients who
      met DSM-IV criteria for both MDD and insomnia (n = 545) received morning
      fluoxetine and were randomized to nightly eszopiclone 3 mg (ESZ+FLX) or placebo
      (PBO+FLX) for 8 weeks. Subjective sleep and daytime function were assessed
      weekly. Depression was assessed with the 17-item Hamilton Rating Scale for
      Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-I) and
      Severity items (CGI-S). RESULTS: Patients in the ESZ+FLX group had significantly
      decreased sleep latency, wake time after sleep onset (WASO), increased total
      sleep time (TST), sleep quality, and depth of sleep at all double-blind time
      points (all p < .05). Eszopiclone co-therapy also resulted in: significantly
      greater changes in HAM-D-17 scores at Week 4 (p = .01) with progressive
      improvement at Week 8 (p = .002); significantly improved CGI-I and CGI-S scores
      at all time points beyond Week 1 (p < .05); and significantly more responders
      (59% vs. 48%; p = .009) and remitters (42% vs. 33%; p = .03) at Week 8. Treatment
      was well tolerated, with similar adverse event and dropout rates. CONCLUSIONS: In
      this study, eszopiclone/fluoxetine co-therapy was relatively well tolerated and
      associated with rapid, substantial, and sustained sleep improvement, a faster
      onset of antidepressant response on the basis of CGI, and a greater magnitude of
      the antidepressant effect.

PMID- 16581037
TI  - Mice with mutations in the HPA-system as models for symptoms of depression.
AB  - Genetically engineered mice hold promise to help us understand the effects of
      enhanced or reduced gene activity upon behavior and metabolism. Because many
      basic and clinical studies suggest that alterations of the hypothalamic pituitary
      adrenocortical (HPA) system are involved in the development and course of
      depression, mouse mutants with genetic modifications of genes regulating the HPA
      system were generated. This review summarizes these effects and concludes that
      advanced technologies allowing for regional overexpression or inactivation of
      genes or introduction of polymorphisms into the mouse genome are well suited to
      explain individual symptoms or symptom patterns prevalent among depressives.
      However, as depression is a complex disorder in which minor changes of many genes
      as well as environmental factors (including epigenetic programming) play a causal
      role and determine the phenotype, the use of mice with single gene mutations
      needs to be critically discussed when attempting to create a genetic animal model
      of depression.

PMID- 16581038
TI  - Zinquin identifies subcellular compartmentalization of zinc in cortical neurons.
      Relation to the trafficking of zinc and the mitochondrial compartment.
AB  - Zinquin (Zn(2+) selective fluorophore), when used to visualize intracellular
      Zn(2+), typically shows brightly fluorescent perinuclear endosome-like
      structures, presumably identifying Zn(2+) containing organelles. In this study,
      zinquin identified numerous and widespread sites of Zn(2+) compartmentalization
      in primary cultures of embryonic rat cortical neurons. Nuclear fluorescence,
      however, was absent. We labeled neuronal mitochondria with MitoTracker Green in
      the presence of zinquin and show that the fluorescent patterns of MitoTracker
      Green and zinquin were distinct and clearly different in both the perinuclear
      region and in processes. The mitochondrial compartment was much larger than the
      sum of the areas of zinquin fluorescence, as indicated by the small amount (<10%
      MitoTracker Green over zinquin) of overlap of MitoTracker Green on zinquin.
      Zinquin fluorescence was unaffected by carbonyl cyanide 4
      (trifluoromethoxy)phenylhydrazone (FCCP) treatment. The zinquin fluorescent
      objects were generally spherical in shape with a average diameter of about 0.6
      mum. Most fluorescent objects, nearly two thirds on average, appeared to be
      docked, but both anterograde and retrograde movements were observed by time lapse
      image analysis. Although some fluorescent objects moved as much as 1 mum in 5
      min, typical movements were smaller, usually 0.5 mum or less. Colchicine
      treatment caused striking aggregation of MitoTracker Green most noticeable in the
      perinuclear region. Zinquin fluorescence similarly showed reduced distribution
      throughout the cytoplasm, suggesting that zinquin fluorescent structures were
      associated with microtubules. Treatment with cytochalasin D had little noticeable
      effect on either the pattern of zinquin and MitoTracker Green fluorescence or
      their coincidence. Thus, numerous Zn(2+) sequestering organelles/structures are
      present in perinuclear regions and processes of cultured neurons and are
      sometimes found coincident with mitochondria. We demonstrated real time
      trafficking of sequestered Zn(2+), using zinquin fluorescence, apparently
      associated with an endosome-like compartment or protein complexes in the cytosol.

PMID- 16581039
TI  - Cerebral plasmalogens and aldehydes in senescence-accelerated mice P8 and R1: a
      comparison between weaned, adult and aged mice.
AB  - In contrast with senescence-accelerated mice R1, SAM P8 show abnormal aging
      characteristics. Changes occurring during aging could be mainly caused by free
      radical reactions. The brain is a plasmalogen-rich tissue. These particular
      phospholipids may act as endogenous antioxidants, be oxidized and release long
      chain aldehydes and alpha-hydroxyaldehydes during oxidative stress. The aim of
      this study was to examine by GC/MS the age- and strain-related levels of
      plasmalogens, aldehydes and alpha-hydroxyaldehydes in brain homogenates of SAM P8
      and R1 at weaning, 5 months and 9 months of age in order to better understand the
      differences between both strains. In SAM R1, the evolution of brain plasmalogen
      levels corresponded to characteristics of normal aging: an increase from weaned
      to adult mice followed by a decrease characterizing the normal loss of myelin. By
      contrast to SAM R1, there was no change in the plasmalogen content in SAM P8
      brain. The levels of aldehydes and alpha-hydroxyaldehydes were similar for both
      strains, they remained constant between adult and aged mice. Specific changes in
      the aging of SAM P8 were not explained by cerebral levels of these oxidative
      products. Other mechanisms related to the toxicity of aldehydes and alpha
      hydroxyaldehydes could be considered.

PMID- 16581040
TI  - Anisomycin activates p38 MAP kinase to induce LTD in mouse primary visual cortex.
AB  - Anisomycin is both a well-established protein synthesis inhibitor and a potent
      activator of the p38/JNK MAPK pathway. It has been used to block the late phase
      of long-term potentiation (LTP) and long-term depression (LTD) in hippocampus. In
      this study, we have found that anisomycin produces a time-dependent decline in
      the magnitude of the field EPSP (fEPSP) in acute brain slices of mouse primary
      visual cortex. This anisomycin-mediated fEPSP depression occludes NMDA receptor
      dependent LTD induced by low-frequency stimulation (LFS). In contrast, two other
      protein synthesis inhibitors, emetine and cycloheximide, have no effect either on
      baseline synaptic transmission or on LTD. Moreover, the decline of the fEPSP
      caused by anisomycin can be rescued by the application of the p38 inhibitor
      SB203580 but not by the JNK inhibitor SP600125. These results indicate that
      activation of p38 MAPK by anisomycin induces LTD and subsequently occludes
      electrically induced LTD. Also, the occlusion of LFS-LTD by anisomycin suggests
      that common mechanisms may be shared between the two forms of synaptic
      depression. Consistent with this view, bath application of a membrane permeant
      peptide derived from the carboxyl tail of GluR2 subunit of AMPA receptor, which
      specifically blocks regulated AMPA receptor endocytosis, thereby preventing the
      expression of LFS-induced LTD, significantly reduced the anisomycin-induced
      decline of the fEPSP. In conclusion, our results indicate that anisomycin
      produces long-lasting depression of AMPA receptor-mediated synaptic transmission
      by activating p38 MAPK-mediated endocytosis of APMA receptors in mouse primary
      visual cortex.

PMID- 16581041
TI  - Differential tissue distribution of tryptophan hydroxylase isoforms 1 and 2 as
      revealed with monospecific antibodies.
AB  - Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of the
      neurotransmitter serotonin. Once thought to be a single-gene product, TPH is now
      known to exist in two isoforms-TPH1 is found in the pineal and gut, and TPH2 is
      selectively expressed in brain. Heretofore, probes used for localization of TPH
      protein or mRNA could not distinguish between the TPH isoforms because of
      extensive homology shared by them at the nucleotide and amino acid level. We have
      produced monospecific polyclonal antibodies against TPH1 and TPH2 using peptide
      antigens from nonoverlapping sequences in the respective proteins. These
      antibodies allow the differentiation of TPH1 and TPH2 upon immunoblotting,
      immunoprecipitation, and immunocytochemical staining of tissue sections from
      brain and gut. TPH1 and TPH2 antibodies do not cross-react with either tyrosine
      hydroxylase or phenylalanine hydroxylase. Analysis of mouse tissues confirms that
      TPH1 is the predominant form expressed in pineal gland and in P815 mastocytoma
      cells with a molecular weight of 51 kDa. TPH2 is the predominant enzyme form
      expressed in brain extracts from mesencephalic tegmentum, striatum, and
      hippocampus with a molecular weight of 56 kDa. Antibody specificity against TPH1
      and TPH2 is retained across mouse, rat, rabbit, primate, and human tissues.
      Antibodies that distinguish between the isoforms of TPH will allow studies of the
      differential regulation of their expression in brain and periphery.

PMID- 16581042
TI  - Possible involvement of 5alpha-reduced neurosteroids in adrenergic and
      serotonergic stimulation of GFAP gene expression in rat C6 glioma cells.
AB  - Influence of adrenergic and serotonergic stimulation on glial fibrillary acidic
      protein (GFAP) gene expression in rat C6 glioma cells was first examined as an in
      vitro model experiment for investigating the neuronal regulation of glial cell
      differentiation. Stimulation of these cells with isoproterenol and serotonin
      elevated GFAP mRNA levels followed by an increase in its protein contents, thus
      suggesting that both adrenergic and serotonergic stimulation might induce the
      differentiation of the glioma cells. In addition, progesterone and its 5alpha
      reduced metabolite dihydroprogesterone also elevated GFAP mRNA levels in rat C6
      glioma cells, consistent with their stimulatory actions on GFAP gene expression
      observed in rat astrocytes. Further studies showed that the elevation of GFAP
      mRNA levels induced by isoproterenol and serotonin as well as progesterone was
      abolished by pretreatment of the glioma cells with finasteride, an inhibitor of
      5alpha-reduced steroid production. Moreover, the stimulatory actions of
      isoproterenol and serotonin on GFAP gene expression were inhibited by
      pretreatment with a GABA(A) receptor antagonist bicuculline and a progesterone
      receptor antagonist RU486. These findings suggest that both adrenergic and
      serotonergic stimulation may indirectly activate GFAP gene expression probably
      through the production of 5alpha-reduced steroid metabolites in rat C6 glioma
      cells, proposing the possibility that 5alpha-reduced neurosteroids may play a
      potential role in the neuronal regulation of glial cell differentiation.

PMID- 16581043
TI  - Redox regulation of cardiac calcium channels and transporters.
AB  - Intracellular concentrations of redox-active molecules can significantly increase
      in the heart as a result of activation of specific signal transduction pathways
      or the development of certain pathophysiological conditions. Changes in the
      intracellular redox environment can affect many cellular processes, including the
      gating properties of ion channels and the activity of ion transporters. Because
      cardiac contraction is highly dependent on intracellular Ca(2+) levels
      ([Ca(2+)](i)) and [Ca(2+)](i) regulation, redox modification of Ca(2+) channels
      and transporters has a profound effect on cardiac function. The sarcoplasmic
      reticulum (SR) Ca(2+) release channel, or ryanodine receptor (RyR), is one of the
      well-characterized redox-sensitive ion channels in the heart. The redox
      modulation of RyR activity is mediated by the redox modification of sulfhydryl
      groups of cysteine residues. Other key components of cardiac excitation
      contraction (e-c) coupling such as the SR Ca(2+) ATPase and L-type Ca(2+) channel
      are subject to redox modulation. Redox-mediated alteration of the activity of ion
      channels and pumps is directly involved in cardiac pathologies such as ischemia
      reperfusion injury. Significant bursts of reactive oxygen species (ROS)
      generation occur during reperfusion of the ischemic heart, and changes in the
      activity of the major components of [Ca(2+)](i) regulation, such as RyR, Na(+)
      Ca(2+) exchange and Ca(2+) ATPases, are likely to play an important role in
      ischemia-related Ca(2+) overload. This article summarizes recent findings on
      redox regulation of cardiac Ca(2+) transport systems and discusses contributions
      of this redox regulation to normal and pathological cardiac function.

PMID- 16581044
TI  - Mitochondrial permeability transition pore and postconditioning.
AB  - Postconditioning has recently been described as a powerful cardioprotection that
      prevents lethal reperfusion injury. Growing evidence suggests that mitochondrial
      permeability transition may be a key event in postconditioning. This proposition
      arises from the complementary observations that: (1) conditions for the
      mitochondrial permeability transition pore (mPTP) opening are built up during
      early reperfusion, (2) mPTP opens at the time of reperfusion, (3) transgenic
      structural alteration of mPTP modifies its opening probability following ischemia
      reperfusion, (4) mPTP plays a role in preconditioning, and (5) postconditioning
      attenuates lethal reperfusion injury. We review in this article current evidence
      for an important role of the mitochondrial transition pore in postconditioning.

PMID- 16581046
TI  - On the species-specific biotransformation of dibenzo[a,l]pyrene.
AB  - We were aimed at investigating the activation of the carcinogenic polycyclic
      aromatic hydrocarbon (PAH) dibenzo[a,l]pyrene (DB[a,l]P) in Chinese hamster V79
      cells that express single human, rat or fish cytochrome P450 (CYP) enzymes.
      DB[a,l]P is detectable in environmental samples and has been characterized as the
      most potent carcinogenic species among all PAHs as yet tested in rodent
      bioassays. Metabolite profiles and metabolite-dependent cytotoxic and clastogenic
      activities were monitored. The total turnover of CYP-mediated transformation of
      DB[a,l]P was as follows: human CYP1B1>fish CYP1A1 approximately human CYP1A1>>rat
      CYP1A2>rat CYP1A1. By contrast, enzyme forms that are not classified as being
      members of family CYP1, such as CYP2A6, 2E1, 2B1, and 3A4, failed to catalyze any
      detectable conversion of this substrate. All CYP1A1 enzymes tested formed both
      the K-region trans-8,9- and the trans-11,12-dihydrodiol, whereas human CYP1B1
      failed to catalyze K-region activation. In cells expressing human or fish CYP1A1,
      human CYP1B1, and rat CYP1A2, the (-)-trans-11,12-dihydrodiol was formed
      enantiospecifically. DB[a,l]P-dependent cytotoxicities (EC(50)) were found in the
      following order: human CYP1A1 (12 nM)>fish CYP1A1 (30 nM)>human CYP1B1 (45
      nM)>>other forms. In addition, an appreciable micronuclei formation was detected
      in human CYP1A1- and 1B1-expressing cells during exposure to DB[a,l]P. Our study
      demonstrates that human CYP1A1, 1B1 and fish CYP1A1 are able to transform
      DB[a,l]P into genotoxic derivatives in appreciable amounts. In contrast, CYP
      enzymes from rat predominantly target the K-region of DB[a,l]P and thus are
      serving more a rather protective route of biotransformation. Together our data
      suggest that humans might be more susceptible to DB[a,l]P-induced carcinogenicity
      than rats.

PMID- 16581045
TI  - IL-1beta and TNF-alpha induce increased expression of CCL28 by airway epithelial
      cells via an NFkappaB-dependent pathway.
AB  - CCL28 is a mucosal chemokine that attracts eosinophils and T cells via the
      receptors CCR3 and CCR10. Consequently, it is a candidate mediator of the
      pathology associated with asthma. This study examined constitutive and induced
      expression of CCL28 by A549 human airway epithelial-like cells. Real-time RT-PCR
      and ELISA of cultured cells and supernatants revealed constitutive levels of
      CCL28 expression to be low, whereas IL-1beta and TNF-alpha, induced significantly
      increased expression. Observations from induced sputum and human airway biopsies
      supported this. Signal transduction studies revealed that IL-1beta and TNF-alpha
      stimulation induced NFkappaB phosphorylation in A549 cells, but antagonist
      inhibition of NFkappaB p50-p65 phosphorylation correlated with marked reduction
      of IL-1beta or TNF-alpha induced CCL28 expression. Together these studies imply a
      role for CCL28 in the orchestration of airway inflammation, and suggest that
      CCL28 is one link between microbial insult and the exacerbation of pathologies
      such as asthma, through an NFkappaB-dependent mechanism.

PMID- 16581047
TI  - Modulation of hypercholesterolemia-induced alterations in apolipoprotein B and
      HMG-CoA reductase expression by selenium supplementation.
AB  - Various studies demonstrated a significant association between the trace element
      selenium (Se), hypercholesterolemia and the risk of cardiovascular disorders.
      Present study was aimed to reveal the role of Se supplementation in modulation of
      hypercholesterolemia-induced changes in apolipoprotein B (apoB) and 3-hydroxy 3
      methylglutaryl co-enzyme A (HMG-CoA) reductase expression during experimental
      hypercholesterolemia in Sprague-Dawley male rats. Animals were fed 0.2 and 1 ppm
      Se-supplemented control diet as well as 2% cholesterol-supplemented diet for 3
      months. Apolipoprotein B levels were measured by ELISA and Western blot. HMG-CoA
      reductase mRNA expression was studied by RT-PCR. ApoB levels increased
      significantly on 2% cholesterol-supplemented diet feeding. On 1 ppm Se
      supplementation apoB levels decreased significantly. HMG-CoA reductase mRNA
      expression decreased significantly on cholesterol-supplemented diet feeding and
      on 1 ppm Se supplementation the mRNA expression further decreased. So the present
      results demonstrate that 1 ppm Se supplementation is responsible for down
      regulation of apoB and HMG-CoA reductase expression during hypercholesterolemia.
      These findings highlight the therapeutic potential of selenium supplementation in
      lipid metabolism.

PMID- 16581048
TI  - Free radical oxidation of 15-(S)-hydroxyeicosatetraenoic acid with the Fenton
      reagent: characterization of an epoxy-alcohol and cytotoxic 4-hydroxy-2E-nonenal
      from the heptatrienyl radical pathway.
AB  - The oxidation of (5Z,8Z,11Z,13E,15S)-15-hydroxy-5,8,11,13-eicosatetraenoic acid
      (15-(S)-HETE, 1a) with the Fenton reagent (Fe2+/EDTA/H2O2) was investigated. In
      phosphate buffer, pH 7.4, the reaction proceeded with 75% substrate consumption
      after 1 h to give a mixture of products, one of which was identified as (2E,4S)-4
      hydroxy-2-nonenal (3a, 18% yield). Methylation of the mixture with diazomethane
      allowed isolation of another main product which could be identified as methyl
      (5Z,8Z,13E)-11,12-trans-epoxy-15-hydroxy-5,8,13-eicosatrienoate (2a methyl ester,
      8% yield). A similar oxidation carried out on (15-(2)H)-15-HETE (1b) indicated
      complete retention of the label in 2b methyl ester and 3b, consistent with an
      oxidation pathway involving as the primary event H-atom abstraction at C-10.
      Overall, these results support the recently proposed role of 1a as a potential
      precursor of the cytotoxic gamma-hydroxyalkenal 3a and disclose a hitherto
      unrecognized interconnection between 1a and the epoxy-alcohol 2a, previously
      implicated only in the metabolic transformations of the 15-hydroperoxy derivative
      of arachidonic acid.

PMID- 16581049
TI  - Folding kinetics of the outer membrane proteins OmpA and FomA into phospholipid
      bilayers.
AB  - The folding mechanism of outer membrane proteins (OMPs) of Gram-negative bacteria
      into lipid bilayers has been studied using OmpA of E. coli and FomA of F.
      nucleatum as examples. Both, OmpA and FomA are soluble in unfolded form in urea
      and insert and fold into phospholipid bilayers upon strong dilution of the
      denaturant urea. OmpA is a structural protein and forms a small ion channel,
      composed of an 8-stranded transmembrane beta-barrel domain. FomA is a voltage
      dependent porin, predicted to form a 14 stranded beta-barrel. Both OMPs fold into
      a range of model membranes of very different phospholipid compositions. Three
      membrane-bound folding intermediates of OmpA were discovered in folding studies
      with dioleoylphosphatidylcholine bilayers that demonstrated a highly synchronized
      mechanism of secondary and tertiary structure formation of beta-barrel membrane
      proteins. A study on FomA folding into lipid bilayers indicated the presence of
      parallel folding pathways for OMPs with larger transmembrane beta-barrels.

PMID- 16581050
TI  - Chondroitin sulfate in normal human plasma is modified depending on the age. Its
      evaluation in patients with pseudoxanthoma elasticum.
AB  - Plasma chondroitin sulfate (CS) amount and charge density were determined in 45
      healthy volunteers (control group), 45 pseudoxanthoma elasticum (PXE)-affected
      patients and 19 healthy carriers by using fluorophore-assisted carbohydrate
      electrophoresis (FACE) and HPLC equipped with postcolumn derivatization and
      fluorescence detection. The mean values of CS amount were 4.9+/-1.21 for
      volunteers, 4.7+/-1.40 for PXE subjects and 4.4+/-1.44 for the carriers. No
      significant differences were found for the three human subjects groups. On the
      contrary, by considering the age of normal volunteers, a significant increase of
      plasma CS amount was measured. In fact, the volunteers aging from 17 to 40 years
      (mean 32.1) showed a CS concentration of 4.3+/-1.30 while the group ranging from
      50 to 74 years (mean 56.9) had a value of 5.6+/-1.16 with a significant increase
      of +30.2%. The same significant increase in CS plasma content with increasing age
      was measured for PXE-affected and healthy carriers group. Extracted plasma CS was
      evaluated for the main two unsaturated disaccharides, non-sulfated and 4
      monosulfated, and the charge density determined. The mean values were 0.54+/-0.13
      for volunteers, 0.60+/-0.15 for PXE subjects and 0.50+/-0.15 for the carriers. A
      significant increase of +11.1% was found between the PXE patients and healthy
      human group but no differences were calculated between the control group and the
      carriers. Furthermore, besides a CS amount, the volunteers aging from 17 to 40
      years (mean 32.1) showed a charge density of 0.53+/-0.14 while the group ranging
      from 50 to 74 years (mean 56.9) had a value of 0.58+/-0.17 with a significant
      increase of +9.4%. The same trend was measured for the healthy carriers group.
      The CS charge density of PXE-affected subjects was found to increase
      significantly more than healthy controls depending on the age. In fact, the PXE
      patients aging from 10 to 40 years (mean 29.3) showed a charge density of 0.56+/
      0.14 while the group ranging from 50 to 74 years (mean 58.6) had a value of
      0.67+/-0.11 with a significant increase of +19.6%. Furthermore, the group of PXE
      affected subjects ranging from 50 to 74 years (mean 58.6) showed a significant
      increase of 15.5% in comparison with the group matched for age (mean 56.9) of
      healthy volunteers.

PMID- 16581051
TI  - Relationships between the level of matrix metalloproteinase-2 and tumor size of
      breast cancer.
AB  - BACKGROUND: The involvements of matrix metalloproteinase-2 (MMP-2) in the
      pathogenesis of breast cancers have been established. We determined the
      concentrations of MMP-2 in serum samples and tumor tissues of breast cancer
      patients. METHODS: Gelatin zymography and ELISA were used to measure MMP-2 and
      MMP-9 concentrations in 90 breast cancer patients, including 60 tissue samples
      and 30 serum samples. RESULTS: ProMMP-2, activated MMP-2, proMMP-9 and activated
      MMP-9 levels were significantly higher in tumor tissues than that of
      corresponding paired adjacent normal tissue of 60 breast cancer patients
      (p<0.01). Further linear regression analysis has showed that the tumor size
      positively correlated with MMP-2 level in tumor tissue samples (R=0.55,
      p<0.0001), as well as with that of in serum samples (R=0.398, p=0.032). In
      addition, further statistical analysis for clinic pathological parameters
      revealed that MMP-2 level was significantly increased in patients with metastasis
      (p<0.05). Furthermore, MMP-2 level was significantly different between tumor
      grades (p=0.006). CONCLUSIONS: MMP-2 levels in serum and tumor tissue might
      reflect the severity of invasion of breast cancer and various MMP inhibitors
      might be selectively used as potential anti-metastasis agents according to tumor
      size.

PMID- 16581052
TI  - The role of language in mathematical development: evidence from children with
      specific language impairments.
AB  - A sample (n=48) of eight-year-olds with specific language impairments is compared
      with age-matched (n=55) and language matched controls (n=55) on a range of tasks
      designed to test the interdependence of language and mathematical development.
      Performance across tasks varies substantially in the SLI group, showing profound
      deficits in production of the count word sequence and basic calculation and
      significant deficits in understanding of the place-value principle in Hindu
      Arabic notation. Only in understanding of arithmetic principles does SLI
      performance approximate that of age-matched-controls, indicating that principled
      understanding can develop even where number sequence production and other aspects
      of number processing are severely compromised.

PMID- 16581053
TI  - Reasoning about artifacts at 24 months: the developing teleo-functional stance.
AB  - From the age of 2.5, children use social information to rapidly form enduring
      function-based artifact categories. The present study asked whether even younger
      children likewise constrain their use of objects according to teleo-functional
      beliefs that artifacts are "for" particular purposes, or whether they use objects
      as means to any desired end. Twenty-four-month-old toddlers learned about two
      novel tools that were physically equivalent but perceptually distinct; one tool
      was assigned implicit function information through a short demonstration. At
      test, toddlers returned to the demonstrated tool when asked to repeat the task,
      but, unlike older children, also used it for another task. Results imply that at
      24 months, toddlers expect artifacts to have functions and proficiently use a
      model's intentional use to inform tool choices, suggesting cognition that differs
      from that of tool-using monkeys. However, their artifact representations are not
      yet specified enough to support exclusive patterns of tool use.

PMID- 16581054
TI  - The role of input and output modality pairings in dual-task performance: evidence
      for content-dependent central interference.
AB  - Recent debate regarding dual-task performance has focused on whether costs result
      from limitations in central capacity, and whether central operations can be
      performed in parallel. While these questions are controversial, the dominant
      models of dual-task performance share the assumption that central operations are
      generic--that is, their interactions are independent of stimulus and response
      modalities. To examine these issues, we conducted a series of dual-task
      experiments with different input and output modality pairings. One condition
      combined a visual-manual task with an auditory-vocal task, and the other
      condition reversed the input-output pairings, combining a visual-vocal task with
      an auditory-manual task. Input/output modality pairings proved to be a key
      factor; throughout practice, dual-task costs were generally more than twice as
      large with visual-vocal/auditory-manual tasks than with the opposite arrangement
      of modalities (Experiments 1 and 2). These differences could be explained neither
      by competition for peripheral resources nor by differences in single-task
      response times (Experiment 3). Moreover, the persistent dual-task costs did not
      appear to stem from a central bottleneck. Contrary to the dominant models of dual
      task performance, we propose that central interference between tasks depends not
      just on the duration of central operations, nor just strategic adaptation, but
      also on the content of those operations. Implications for structural and
      strategic accounts of dual-task interference are discussed.

PMID- 16581055
TI  - Comprehensive microarray analysis of Hoxa11/Hoxd11 mutant kidney development.
AB  - The Hox11 paralogous genes play critical roles in kidney development. They are
      expressed in the early metanephric mesenchyme and are required for the induction
      of ureteric bud formation and its subsequent branching morphogenesis. They are
      also required for the normal nephrogenesis response of the metanephric mesenchyme
      to inductive signals from the ureteric bud. In this report, we use microarrays to
      perform a comprehensive gene expression analysis of the Hoxa11/Hoxd11 mutant
      kidney phenotype. We examined E11.5, E12.5, E13.5 and E16.5 developmental time
      points. A novel high throughput strategy for validation of microarray data is
      described, using additional biological replicates and an independent microarray
      platform. The results identified 13 genes with greater than 3-fold change in
      expression in early mutant kidneys, including Hoxa11s, GATA6, TGFbeta2, chemokine
      ligand 12, angiotensin receptor like 1, cytochrome P450, cadherin5, and
      Lymphocyte antigen 6 complex, Iroquois 3, EST A930038C07Rik, Meox2, Prkcn, and
      Slc40a1. Of interest, many of these genes, and others showing lower fold
      expression changes, have been connected to processes that make sense in terms of
      the mutant phenotype, including TGFbeta signaling, iron transport, protein kinase
      C function, growth arrest and GDNF regulation. These results identify the
      multiple molecular pathways downstream of Hox11 function in the developing
      kidney.

PMID- 16581056
TI  - The canonical Notch/RBP-J signaling pathway controls the balance of cell lineages
      in mammary epithelium during pregnancy.
AB  - Mammary alveoli are composed of luminal (secretory) and basal (myoepithelial)
      cells, which are descendants of a common stem cell. This study addressed the role
      of RBP-J-dependent Notch signaling in the formation, maintenance and cellular
      composition of alveoli during pregnancy. For this purpose, the genes encoding RBP
      J, the shared transcriptional mediator of Notch receptors, and Pofut1, a
      fucosyltransferase required for the activity of Notch receptors, were deleted in
      mammary progenitor cells in the mouse using Cre-mediated recombination. Loss of
      RBP-J and Pofut1 led to an accumulation of basal cell clusters characterized by
      the presence of cytokeratins (K5) and K14 and smooth muscle actin (SMA) during
      pregnancy. Hormonal stimulation of mutant tissue induced the expression of the
      basal cell transcription factor p63 in luminal cells and excessive proliferation
      of basal cells. A transient enrichment of K6-positive luminal cells was observed
      upon hormonal treatment suggesting a temporary arrest at an immature stage prior
      to transdifferentiation and expansion as basal cells. Despite the extensive
      proliferation of RBP-J-null basal cells during pregnancy, hormonal withdrawal
      during involution resulted in complete remodeling and the restoration of normal
      tissue architecture. We propose that the Notch-RBP-J pathway regulates alveolar
      development during pregnancy by maintaining luminal cell fate and preventing
      uncontrolled basal cell proliferation.

PMID- 16581057
TI  - Olig2-positive progenitors in the embryonic spinal cord give rise not only to
      motoneurons and oligodendrocytes, but also to a subset of astrocytes and
      ependymal cells.
AB  - Motoneurons and oligodendrocytes in the embryonic spinal cord are produced from a
      restricted domain of the ventral ventricular zone, termed the pMN domain. The pMN
      domain is the site of expression of two basic helix-loop-helix transcription
      factors, Olig1 and Olig2, which are essential for motoneuron and oligodendrocyte
      development. Previous lineage-tracing experiments using Olig1-Cre and Olig2-GFP
      mice suggested that motoneurons and oligodendrocytes, but not astrocytes, are
      produced from the pMN domain. However, important questions remain, including the
      fate of neuroepithelial cells in the pMN domain, and specifically whether
      motoneurons and oligodendrocytes are the only types of cells produced in the pMN
      domain. We performed lineage-tracing experiments using a tamoxifen-inducible Cre
      recombinase inserted into the Olig2 locus. We demonstrated that motoneurons and
      oligodendrocyte progenitors are derived from the Olig2+ progenitors in the pMN
      domain, and also found that a subset of astrocytes at the ventral surface of the
      spinal cord and ependymal cells at the ventricular surface are also produced from
      the pMN domain. These findings demonstrate that motoneurons and oligodendrocytes
      are not the only cell types originating from this domain.

PMID- 16581058
TI  - A subpial, transitory germinal zone forms chains of neuronal precursors in the
      rabbit cerebellum.
AB  - Protracted neurogenesis occurs at different postnatal stages in different brain
      locations, whereby leading to site-specific adult neurogenesis in some cases. No
      spontaneous genesis of neurons occurs in the cerebellum after the postnatal
      genesis of granule cells from the external germinal layer (EGL), a transitory
      actively proliferating zone which is thought to be exhausted before puberty.
      Here, we show the protracted genesis of newly generated neuronal precursors in
      the cerebellar cortex of young rabbits, persisting beyond puberty. Neuroblasts
      generated within an actively proliferating subpial layer thus extending the
      postnatal EGL are arranged to form thousands of tangential chains reminiscent of
      those responsible for cell migration in the forebrain subventricular zone. These
      subpial chains cover the whole cerebellar surface from the 2nd to the 5th month
      of life, then disappearing after puberty. In addition, we describe the appearance
      of similar groups of cells at the end of granule cell genesis in the mouse
      cerebellum, here limited to the short period of EGL exhaustion (4-5 days). These
      results show common features do exist in the postnatal reorganization of
      secondary germinal layers of brain and cerebellum at specific stages, parallel to
      differences in the slowing down of cerebellar neurogenesis among mammalian
      species.

PMID- 16581059
TI  - Expression and function of blimp1/krox, an alternatively transcribed regulatory
      gene of the sea urchin endomesoderm network.
AB  - The blimp1/krox gene of Strongylocentrotus purpuratus, formerly krox1, encodes
      zinc finger transcription factors which play a central role in both early and
      late endomesoderm specification. Here we show that there are two alternative
      splice forms transcribed under the control of different regulatory regions. The
      blimp/krox1b form was previously unknown, and is the form expressed during
      cleavage, beginning 6-9 h postfertilization. This form is required for the early
      events of endomesoderm specification. A different splice variant, blimp1/krox1a,
      is expressed only from gastrula stage onward. During cleavage stages the
      blimp1/krox gene is expressed in the large micromeres and veg2 descendents. Soon
      after, it is expressed in the ring of specified mesoderm cells at the vegetal
      pole of the blastula. Its expression is later restricted to the blastopore region
      and the posterior of the invaginating archenteron, and finally to the midgut and
      hindgut of the pluteus larva. The expression of blimp1/krox is dynamic, and
      involves several distinct spatial territories. A GFP recombinant BAC was created
      by substituting the GFP coding sequence for that of the second exon (1b), in
      order to distinguish the expression pattern of the early form from that of the
      late form. This construct closely mimics blimp1/krox1b expression during early
      stages of sea urchin development. To expand our knowledge of the downstream
      linkages of this gene, additional experiments were carried out using antisense
      morpholino oligos (MASO). We confirmed previously published data that blimp1/krox
      autoregulates its own expression, but discovered, surprisingly, that this gene
      represses rather than activates itself. This negative autoregulation is
      restricted to the mesodermal and probably skeletogenic territories during the
      blastula stage, as shown by in situ hybridization analysis of MASO injected
      embryos. The MASO perturbation analysis also revealed blimp1/krox inputs into
      other genes of the endomesoderm regulatory network.

PMID- 16581060
TI  - Evaluation of repeated measurements of radon-222 concentrations in well water
      sampled from bedrock aquifers of the Piedmont near Richmond, Virginia, USA:
      effects of lithology and well characteristics.
AB  - Radon (222Rn) concentrations in 26 ground water wells of two distinct lithologies
      in the Piedmont of Virginia were measured to assess variation in ground water
      radon concentrations (GWRC), to evaluate differences in concentrations related to
      well characteristics, lithology, and spatial distributions, and to assess the
      feasibility of predicting GWRC. Wells were sampled in accordance with American
      Public Health Association Method 7500 Rn-B, with modifications to include a well
      shaft profile analysis that determined the minimum purge time sufficient to
      remove the equivalent of one column of water from each well. Statistically
      significant differences in GWRC were found in the Trssu (1482 +/- 1711 pCi/L) and
      Mpg (7750 +/- 5188 pCi/L) lithologies, however, no significant differences were
      found among GWRC at each well over time. Using multiple regression, 86% of the
      variability (R2) in the GWRC was explained by the lithology, latitudinal class,
      and water table elevation of the wells. The GWRC in a majority of the wells
      studied exceed US Environmental Protection Agency designated maximum contaminant
      level and AMCL. Results support modifications to sampling procedures and indicate
      that, in previous studies, variations in GWRC concentrations over time may have
      been due in part to differences in sampling procedures and not in source water.

PMID- 16581061
TI  - Metal levels in flathead sole (Hippoglossoides elassodon) and great sculpin
      (Myoxocephalus polyacanthocephalus) from Adak Island, Alaska: potential risk to
      predators and fishermen.
AB  - Increasingly there is a need to assess the contaminant levels in fish as
      indicators of the health and well-being of both the fish and their consumers,
      including humans. This paper examines the levels of arsenic, cadmium, chromium,
      lead, manganese, mercury, and selenium in the kidney, liver, and muscle of great
      sculpin and flathead sole from Adak Island in the Aleutian Islands, Alaska. Both
      species are consumed by the local Aleuts and others. There were significant
      differences in the levels of heavy metals as a function of tissue for both fish
      species; the liver of sculpin and sole generally had the highest levels of most
      metals, except for arsenic, lead, and selenium. Sole had significantly higher
      mean levels of arsenic in kidney (32,384 vs. 531 ppb, wet weight), liver (18,954
      vs. 2532 ppb), and muscle (19,452 vs. 1343 ppb) than did sculpin. Sole also had
      higher mean levels of cadmium (230 vs. 63 ppb), lead (1236 vs. 48 ppb), mercury
      (150 vs. 107 ppb), and selenium (5215 vs. 1861 ppb) in kidney than did sculpin.
      There were significant correlations among weight and length measurements for both
      species. However, except for mercury, there were few significant correlations
      among tissue types for most metals. Only mercury and manganese levels were
      significantly correlated with size for sculpin (but not for sole). Levels of
      arsenic, lead, and mercury may pose a risk to predators that consume them, and
      arsenic and mercury may pose a risk to human consumers.

PMID- 16581062
TI  - Prostaglandin I2 release following mesenteric traction during abdominal surgery
      is mediated by cyclooxygenase-1.
AB  - Our study aimed to determine the role of cyclooxygenase-2 in the release of
      prostaglandin-(PG)-I2 following mesenteric traction during abdominal surgery. In
      a prospective double-blind, randomized, placebo-controlled study, 40 patients
      electively scheduled for non-laparoscopic abdominal surgery, were pretreated with
      the cyclooxygenase-2 inhibitor parecoxib (n=20) or placebo (n=20). Heart rate,
      arterial blood pressure, oxygenation ratio and plasma concentrations of the
      stable PGI2-metabolite 6-keto-PGF1alpha were compared between groups before
      injection of parecoxib (-40 min), immediately before mesenteric traction (0 min),
      and 5, 10, and 30 min thereafter. In addition, plasma concentrations of
      valdecoxib, the active metabolite of the prodrug parecoxib, were determined.
      Plasma concentrations of 6-keto-PGF1alpha and heart rate increased in both groups
      after mesenteric traction. There were no significant differences between groups
      at individual times in heart rate, arterial blood pressure and plasma
      concentrations of 6-keto-PGF1alpha. Oxygenation ratio decreased after 10 and 30
      min following mesenteric traction in the parecoxib group with a significant
      difference between treatment groups at 10 and 30 min. Plasma concentrations of
      valdecoxib revealed therapeutic values. Our data indicate that PGI2 release
      following mesenteric traction is mediated by cyclooxygenase-1.

PMID- 16581063
TI  - Pirfenidone: anti-fibrotic agent with a potential therapeutic role in the
      management of transplantation patients.
AB  - Pirfenidone has a simple chemical structure, but may have profound implications
      for transplantation management. One of the leading causes of allograft failure is
      chronic allograft dysfunction, manifested by chronic inflammation and chronic
      fibrosis [Estenne, M., Hertz, M.I., 2002. Bronchiolitis obliterans after human
      lung transplantation. AJRCCM. 166, 440-444.]. This review summarizes the
      literature to date on Pirfenidone in the setting of transplantation, and those
      studies pertinent to the mechanisms of organ rejection and possible use of
      Pirfenidone in transplantation patients.

PMID- 16581064
TI  - Short courses of low dose dexamethasone delay bleomycin-induced lung fibrosis in
      rats.
AB  - After comparing mortality and clinical signs in rats receiving different
      dexamethasone treatments, we investigated whether 0.5 mg/kg/d dexamethasone could
      delay pulmonary fibrosis induced by bleomycin and its time course (1, 3, 7, 14,
      21 and 28 days). Tissue injury was assessed by apoptosis, lactate dehydrogenase
      (LDH) release, malondialdehyde content, and protein content; and inflammation was
      measured in terms of myeloperoxidase (MPO) activity, inflammatory cell count, and
      the mRNA expression of pro/inflammatory cytokines. Fibrogenic activity was
      analyzed by measuring the mRNA expression of fibrotic cytokines in tissue, and
      the promotion of fibroproliferation and synthesis of collagen type I by
      bronchoalveolar lavage fluids in vitro; and fibrosis was assessed by measuring
      the hydroxyproline content and collagen-I mRNA expression, and by histology.
      Bleomycin treatment induced tissue injury, inflammation and fibrogenic activity
      in lung, and led to fibrosis. Treatment with dexamethasone diminished the extent
      of fibrosis by strongly reducing inflammation, lung damage, and fibrogenic
      activity. These results demonstrate that the progression of bleomycin-induced
      pulmonary fibrosis in rats can be delayed by dexamethasone treatment, which
      appeared to alleviate not only inflammation but also lung damage and fibrogenic
      activity, indicating a possible new role for dexamethasone in the treatment of
      fibrosis.

PMID- 16581065
TI  - Ghrelin-induced gastroprotection against ischemia-reperfusion injury involves an
      activation of sensory afferent nerves and hyperemia mediated by nitric oxide.
AB  - Ghrelin has been recently identified as an endogenous ligand for growth hormone
      secretagogue receptor that regulates growth hormone secretion, increases appetite
      and contributes to energy homeostasis. Although this peptide is predominantly
      produced by the fasted stomach, little is known about its influence on the
      gastric mucosal integrity. The aim of the present study was (1) to investigate
      the effect of acylated ghrelin on the formation and healing of acute gastric
      mucosal lesions induced by ischemia-reperfusion and gastric mucosal blood flow in
      rats; (2) to analyse the effects of the deactivation of afferent sensory nerves
      with capsaicin and of the inhibition of nitric oxide (NO)-synthase by NG-nitro-l
      arginine (l-NNA) on the ghrelin-induced protection; (3) to examine the influence
      of ghrelin on nuclear factor-kappa B (NF-kappaB) activation and on release of
      proinflammatory cytokines, such as tumor necrosis factor-alpha, (4) to assess the
      effect of ghrelin on the mRNA expression of constitutive nitric oxide synthase
      (cNOS), calcitonin gene related peptide (CGRP) and angiogenesis related proteins
      such as hypoxia inducible factor-1 alpha (HIF-1alpha) and vascular endothelial
      growth factor (VEGF), and (5) to determine the effect of ischemia/reperfusion on
      the gastric mucosa expression of ghrelin in rats without and with administration
      of exogenous hormone. Wistar rats were exposed to 30 min of ischemia followed by
      3 h of reperfusion. Ghrelin was administered in dose of 5, 10 or 20 mug/kg
      intraperitoneally (i.p.) 30 min prior exposure to ischemia/reperfusion and at 3 h
      after the end of ischemia, the mean lesion area was measured by planimetry and
      the changes in gastric blood flow were determined by hydrogen (H2)-gas clearance
      method. The healing of ischemia/reperfusion induced lesions was evaluated at 24 h
      or 6 days after the end of standard ischemia/reperfusion. The expression of cNOS,
      CGRP, HIF-1alpha, VEGF and ghrelin was evaluated by reverse transcription
      polymerase chain reaction or Western blot. Ghrelin significantly attenuated the
      ischemia/reperfusion-induced gastric lesions and accelerated the healing of these
      lesions while significantly raising the gastric blood flow. Deactivation of
      sensory nerves with capsaicin or inhibition of cNOS by L-NNA significantly
      attenuated the protective activity of ghrelin and accompanying increase in the
      GBF. Exogenous ghrelin significantly inhibited the activation of NF-kappaB and
      plasma TNF-alpha levels. The ghrelin-enhanced acceleration of healing of
      ischemia/perfusion induced lesions was accompanied by enhanced expression of mRNA
      for HIF-1alpha and by diminution of the ischemia/reperfusion induced increase in
      mRNA expression for TNF-alpha. We conclude that ghrelin exerts a potent
      protective action on the gastric mucosa and accelerates the healing of
      ischemia/reperfusion-induced lesions and these effects depend upon activation of
      sensory nerves, hyperemia mediated by NO, increased angiogenesis due to
      expression of YEGF and anti-inflammatory properties of this peptide.

PMID- 16581066
TI  - Characterization of adenosine receptors in the human bladder carcinoma T24 cell
      line.
AB  - The molecular and pharmacological properties of adenosine receptors in the T24
      human bladder epithelial carcinoma cell line were assessed by Reverse
      Transcriptase-Polymerase Chain Reaction (RT-PCR), Ca2+ Flux, cAMP production and
      interleukin-8 measurements. RT-PCR experiments detected the presence of
      transcripts for the adenosine A1, A2A and A2B receptors but not for the adenosine
      A3 subtype. Application of specific adenosine receptor ligands resulted in
      concentration-dependent increases in intracellular calcium ([Ca2+]i) with the
      following order of potency and EC50 values: 5'-N-Ethylcarboxamidoadenosine (NECA)
      (1153+/-214)>5'-(N-Cyclopropyl)carboxamidoadenosine (CPCA) (1436+/-186)>adenosine
      (4823+/-932). This rank order of potency is typical of adenosine A2B receptors.
      In addition, select adenosine receptor antagonists N-(4-acetylphenyl)-2-[4
      (2,3,6,7-tetrahydro-2,6 dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]acetamide (MRS
      1706), 8-[4-[((4-Cyano[2,6-]-phenyl)carbamoylmethyl)oxy]phenyl]-1,3-di(n-propyl)
      xanthine (MRS 1754), 1,3-Diethyl-8-phenylxanthine (DPCPX), 1,3-Diethyl-8
      phenylxanthine (DPX), Alloxazine, 8-(3-Chlorostyryl)caffeine (CSC), and
      Theophylline blocked the NECA-induced calcium responses. Additionally, NECA,
      CPCA, and adenosine stimulated cAMP formation with a rank order of potency
      characteristic of adenosine A2B receptors. The select adenosine A2A antagonist, 5
      amino-7-(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]
      pyrimidine (SCH 58261) failed to antagonize the NECA response, whereas the potent
      and highly selective adenosine A2B antagonists MRS 1754 and MRS 1706 inhibited
      NECA-stimulated cAMP production. Lastly, NECA-induced interleukin-8 secretion was
      inhibited by MRS 1754. Taken together, these data indicate that [Ca2+]i
      accumulation and cAMP production as well as interleukin-8 secretion is mediated
      through the adenosine A2B receptor in the T24 cell line.

PMID- 16581067
TI  - Ca2+ channel activating action of maitotoxin in cultured brainstem neurons.
AB  - The actions of maitotoxin were studied using cultured brainstem cells and adrenal
      chromaffin cells. Maitotoxin induced a profound increase in the Ca2+ influx into
      cultured brainstem cells after a brief lag period. The maitotoxin-induced Ca2+
      influx was suppressed by various voltage-dependent Ca2+ channel blockers such as
      Co2+, Mn2+, verapamil and diltiazem. Maitotoxin-catecholamine release in
      brainstem cells initiated to increase after a lag period of about 1 min and the
      increase continued even at 4 min after treatment, while in the adrenal chromaffin
      cells the release started after an about 1-min lag period to attain a maximum
      within first 2-min and gradually decrease thereafter. These results suggest that
      maitotoxin acts on Ca2+ channels to increase the Ca2+ influx, accompanied by
      enhancement of catecholamine release in the brainstem cells with a different
      temporal profile from that in the adrenal chromaffin cells.

PMID- 16581068
TI  - Effects of drugs acting on the GABA-benzodiazepine receptor complex on flurothyl
      induced seizures in Mongolian gerbils.
AB  - In the present study, the mechanism behind flurothyl-induced seizures was
      examined using drugs acting on the GABA-benzodiazepine receptor complex in
      Mongolian gerbils. In addition, amino acid concentrations in the brain were also
      investigated. In behavioral experiments, the incidence of tonic extensor was
      83.3% in both the control and picrotoxin (0.5 mg/kg)-treated groups, 0% in the
      valproate (200 mg/kg)-treated group, and 50% in the picrotoxin plus valproate
      treated group. However, picrotoxin did not antagonize the effect of valproate on
      clonic seizure latency at all. Flumazenil, a benzodiazepine receptor antagonist,
      was found to have an inhibitory effect on the anticonvulsant action of diazepam
      (0.5 mg/kg). The incidence of tonic extensor was 83.3% in flumazenil (10 mg/kg)
      treated group, 0% in the diazepam (0.5 mg/kg)-treated group, and 83% in the
      flumazenil plus diazepam-treated group as well as the control group. Flumazenil
      also completely reversed the effect of diazepam on clonic seizure latency. In
      biochemical experiments, the concentration of the inhibitory amino acid, GABA,
      was significantly increased in the hippocampus (P<0.05) and cerebellum (P<0.01)
      in diazepam-treated animals. The increase of GABA in the hippocampus and
      cerebellum was antagonized by the administration of flumazenil. These results
      suggested that the anticonvulsant action of diazepam may be linked to increase in
      hippocampus and cerebellum GABA concentrations. The findings suggest that the
      mechanism of flurothyl-induced seizures, in part, is related to the highly
      sensitive benzodiazepine site of the GABA-benzodiazepine receptor complex.

PMID- 16581069
TI  - Cytochrome c(6A) is a funnel for thiol oxidation in the thylakoid lumen.
AB  - Cytochrome c(6A) is a dithio-cytochrome recently discovered in land plants and
      green algae, and believed to be derived from the well-known cytochrome c(6). The
      function of cytochrome c(6A) is unclear. We propose that it catalyses the
      formation of disulphide bridges in thylakoid lumen proteins in a single-step
      disulphide exchange reaction, with subsequent transfer of the reducing
      equivalents to plastocyanin. The haem group of cytochrome c(6A) acts as an
      electron sink, allowing rapid resolution of a radical intermediate formed during
      reoxidation of cytochrome c(6A). Our model is consistent with previously
      published data on mutant plants, and the likely evolution of the protein.

PMID- 16581070
TI  - Effect of human presence and handling on circulating corticosterone levels in
      breeding blue tits (Parus caeruleus).
AB  - Birds may react to the presence of humans with an immediate primary behavioural
      reaction and with physiological responses, such as the activation of the
      hypothalamo-pituitary-adrenal axis. This study investigates the suite of
      behavioural and adrenocortical responses to the presence of humans and to
      handling in two subspecies of blue tits Parus caeruleus, a small hole-nesting
      passerine, during the period of feeding their nestlings. The first aim was to
      investigate whether the presence of humans near their nests elicits an
      adrenocortical response and whether the increase in circulating corticosterone is
      correlated with the behavioural reaction of the birds. The second aim was to
      determine the time-lag between the onset of capture and handling stress and the
      increase in circulating corticosterone levels. The third aim was to try to
      explain individual variation in the adrenocortical response to handling with 9
      intrinsic and extrinsic factors (sex, age, body size, measures of body condition,
      time of day, and date). One half of the parents showed a behavioural reaction to
      our presence near the nest, such as alarming, and hesitating to enter the
      nestbox. However, the degree of behavioural reaction before handling was not
      related to circulating corticosterone levels which remained low. The results
      confirm that primary behavioural and adrenocortical reactions to the presence of
      predators are independent of each other. A comparison with published findings
      supports the hypothesis that birds react to predators with an adrenocortical
      response only in a situation that is imminently life-threatening. Hence, the
      primary behavioural response of the bird to a predator may determine whether or
      not an adrenocortical response is elicited. An adrenocortical response to
      handling started 3 min after capture in the nest box. Individual variation in
      baseline corticosterone levels could be explained by subspecies and body
      condition (fat stores), variation in handling-induced corticosterone levels by
      subspecies, body condition, body size, and time of day.

PMID- 16581071
TI  - Progesterone receptor activation signals behavioral transitions across the
      reproductive cycle of the female rabbit.
AB  - The female rabbit is an exceptional experimental model to define mechanisms by
      which progesterone (P) controls the expression of reproductive behaviors. In the
      rabbit, the rise in P levels during pregnancy inhibits estrous scent marking
      ("chinning"), stimulates the excavation of a nest burrow ("digging"), and primes
      behaviors later used for nest construction. The pre-parturient fall of P triggers
      the construction of a straw nest ("straw carrying") that is lined with hair that
      she pulls from her own body ("hair pulling"). These behaviors can be replicated
      in ovariectomized (ovx) females given a schedule of estradiol (E) and P that
      mimics hormone levels during pregnancy (E from days 0 to 4, E + P from days 5 to
      17, E from days 18 to 27). We administered PR antagonists RU486 or CDB(VA)2914 to
      ovx female rabbits during either the initial (days 5-11) or late (days 12-17)
      phases of P treatment, to determine the role of PR activation in coordinating the
      expression of these behaviors. Both antiprogestins attenuated the P-mediated
      decline in chinning and increase in digging when administered during days 5-11.
      When given across days 12-17, both antiprogestins triggered an early decline in
      digging, the onset of nest building in some Ss, and the reinstatement of
      chinning. These results point to a central role of PR activation for establishing
      and maintaining the behavioral phenotype of pregnancy, and for the behavioral
      transition from pregnancy to estrus.

PMID- 16581072
TI  - The role of sex steroids in courtship, pairing and pairing behaviors in the
      socially monogamous zebra finch.
AB  - The purpose of this study was to test whether sex steroid actions are necessary
      for courtship and pairing in socially monogamous birds. We examined the effects
      of an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), combined with
      an anti-androgen, flutamide (F), on the behavior and pairing status of initially
      unpaired male and female zebra finches (Taeniopygia guttata). In the first
      experiment, 24 adult males were implanted with either a combination of ATD and
      flutamide or empty implants. Two weeks after implantation, birds were housed in
      aviaries containing 3 ATD + F males, 3 control males, and 3 females and allowed 2
      weeks to pair, with observations 7 times during the 2-week period. A second
      experiment tested the effects of these same treatments in females. During the
      first 4 days of testing, ATD + F males were less likely to attack conspecifics
      than were control males. ATD + F males were also less likely to "greet," or
      approach, females than were control males, but other courtship behaviors,
      including directed singing, were unaffected. ATD + F females did not differ from
      control females on any courtship behavior measured. Furthermore, these treatments
      did not affect pairing behaviors (time spent clumping or in a nest box together)
      or the likelihood of pairing with a partner of the opposite sex. ATD + F
      treatments in females did, however, increase the likelihood of same-sex pairing.
      This suggests that, although sex steroids may regulate some courtship behaviors
      in males, they do not regulate pairing behaviors and have little effect on the
      likelihood that a male or female will be chosen as a mate by a bird of the
      opposite sex.

PMID- 16581073
TI  - Electric stimulation and hyperbaric oxygen therapy in the treatment of nonunions.
AB  - Up to 10% of the fractures occurring annually in the U.S. end up in non-union or
      delayed union. Classical treatment with osteosynthesis and bone grafting is not
      always successful. Alternatives in treatment have long ago been considered. This
      article presents current concepts in treatment with electrical stimulation and
      hyperbaric oxygen, the mechanisms of action, experimental and clinical evidence
      of their application.

PMID- 16581074
TI  - Vascularised bone grafts for the management of non-union.
AB  - Non-union of the long bones may have severe consequences, particularly when
      combined with other post-traumatic sequelae, such as tendon adhesions, reflex
      sympathetic dystrophy and infection, among others. In these cases, it is
      important to treat the delayed union or non-union first or at the same time with
      the other problems in order to achieve adequate function. Once the normal bony
      healing process has been slowed or stopped, it is necessary to provide both
      stability to the fracture site, as well as a biological stimulus for the
      fibrocartilagenous callus to finish the healing process. Vascularised grafts,
      such as the free fibula, offer not only structural support, but also promote bone
      healing. The later is achieved by trabecular bone formation, as well as vascular
      sprouting from pedicle vessels.

PMID- 16581075
TI  - Gene therapy in orthopaedics.
AB  - Impressive advances in our knowledge of the molecular genetic basis of skeletal
      disorders and fracture healing have led to the development of novel therapeutics
      based on ectopic expression of one or more genes in patient cells that can
      influence repair or regenerative processes in bone. Gene therapy is an attractive
      new approach to the treatment of bone disorders. Orthopaedics has become one of
      the most promising areas of research into gene therapy. This is because many
      potential orthopaedic targets for gene therapy, unlike traditional targets such
      as cancer and severe genetic disorders, neither present difficult delivery
      problems nor require prolonged periods of gene expression. Gene therapy offers
      new possibilities for the clinical management of orthopaedic conditions that are
      difficult to treat by traditional surgical or medical means. Impaired bone
      healing, need for extensive bone formation, cartilage repair and metabolic bone
      diseases are all conditions where alterations of the signalling peptides involved
      may provide cure or improvement. In orthopaedic oncology, gene therapy may
      achieve induction of tumour necrosis and increased tumour sensitivity to
      chemotherapy. An increasing amount of evidence indicates that gene transfer can
      aid the repair of articular cartilage, menisci, intervertebral disks, ligaments
      and tendons. These developments have the potential to transform many areas of
      musculoskeletal care, leading to treatments that are less invasive, more
      effective and less expensive than existing modalities.

PMID- 16581076
TI  - Low-intensity pulsed ultrasound for bone healing: an overview.
AB  - Low-intensity ultrasound is a biophysical form of intervention in the fracture
      repair process, which through several mechanisms accelerates healing of fresh
      fractures and enhances callus formation in delayed unions and nonunions. The goal
      of this review is to present the current knowledge obtained from basic science
      and animal studies, as well as existing evidence from clinical trials and case
      series with the different applications of ultrasound in the management of
      fractures, delayed unions, nonunions and distraction osteogenesis. Low-intensity
      pulsed ultrasound is currently applied transcutaneously, although recent
      experimental studies have proven the efficacy of a trans-osseous application for
      both enhancement and monitoring of the bone healing process with modern smart
      implant technologies.

PMID- 16581077
TI  - Getting it right: Australian primiparas' views about breastfeeding: A quasi
      experimental study.
AB  - BACKGROUND: The study documented Australian primigravidas' perceptions about
      breastfeeding. OBJECTIVES: To examine women's perspectives of their breastfeeding
      experiences during the first 12 weeks postpartum. DESIGN: A Journal was
      introduced to an intervention group (n=149) attending prenatal classes at a
      private hospital at 36 antenatal weeks. Using quantitative data at two days and
      12 weeks postpartum, the intervention group was compared with a control group
      (n=154) that delivered at the same hospital. Qualitative data were also collected
      about the women's perceptions about breastfeeding to further illuminate their
      experience. Qualitative data from 203 women at two days postpartum and 252 women
      at 12 weeks postpartum represented the combined comments from the intervention
      and control groups. PARTICIPANTS: Participants were recruited as part of a
      randomised controlled trial of the effects of a Breastfeeding Journal on
      breastfeeding prevalence, self-efficacy, support, and influence from conflicting
      advice. The convenience sample of middle class, well-educated primiparous women
      from a Western Australian hospital had given birth to a singleton infant that was
      greater than 34 weeks gestation. METHODS: An open-ended question on a
      questionnaire sought mothers' comments about their breastfeeding experiences.
      Data were analysed using inductive content analysis. FINDINGS: These mothers
      described trying to 'get breastfeeding right'. Getting it right included
      enhancing factors, factors with mixed effect, and negative factors. CONCLUSIONS:
      Middle class mothers share breastfeeding perceptions with women in more
      vulnerable groups, including encountering conflicting and unhelpful advice and
      feeding pressures from health care professionals, family, and community members.

PMID- 16581078
TI  - Adiponectin and its gene variants as risk factors for insulin resistance, the
      metabolic syndrome and cardiovascular disease.
AB  - The increasing prevalence of obesity and metabolic syndrome/insulin resistance
      has attracted considerable interest due to their identification as risk factors
      for cardiovascular disease and, hence, targets for cardiovascular disease
      prevention. This review focuses on adiponectin, the most profusely secreted
      protein from adipose tissue, which itself is being increasingly recognised as an
      important and very active endocrine organ, secreting a wide range of biologically
      active substances known as adipokines or adipocytokines. Adiponectin has been
      demonstrated to have insulin sensitising effects, and secretion of adiponectin is
      reduced as adipose tissue mass increases. Adiponectin has also been demonstrated
      to have anti-inflammatory and anti-atherogenic properties, and is independently
      associated with cardiovascular disease. The evidence that suggests adiponectin
      plays a role in the relationship between obesity and insulin resistance, and also
      insulin resistance and cardiovascular disease, is examined. Variation in the
      adiponectin gene is one tool to determine whether this relationship is causal.
      The association of identified variants with human disease, specifically obesity
      and its consequences, type 2 diabetes and cardiovascular disease is reviewed.
      This data may enable patients at greater risk of the adverse effects of obesity
      to be identified and, as such, benefit from more targeted therapy of its
      consequences.

PMID- 16581079
TI  - Optimization and evaluation of a procedure for the gas chromatographic-mass
      spectrometric analysis of the aromas generated by fast acid hydrolysis of flavor
      precursors extracted from grapes.
AB  - A procedure has been developed for the GC-MS analysis of the aromas released in
      fast acid hydrolysis of precursor fractions from grape musts and skins. Different
      sorbents for the extraction of the precursors were compared. The best results
      were obtained with LiChrolut EN polymeric resins which displayed two and six-fold
      more extraction capacity than Amberlite XAD-2 resins and C18 sorbents,
      respectively. C18 sorbents are more suitable for selective extraction of less
      polar precursors. The initial version of the method was imprecise and so the
      imprecision of the different steps was assessed. The maceration of the solid
      parts and the liquid-liquid extraction of the aromas released in the acid
      hydrolysis proved to be the critical steps. Greater crushing of the solid parts
      and solid-phase extraction (SPE) instead of liquid-liquid extraction (LLE)
      improved reproducibility. In the method finally proposed about 100 aromatic
      components belonging to four large groups (lipid derivatives, shikimic acid
      derivatives, norisoprenoids and terpenes) were determined with good
      reproducibility. Important aroma compounds, such as cis-rose oxide or wine
      lactone were detected in non-Muscat grapes.

PMID- 16581080
TI  - Scale-up of chromatographic ion-exchange processes in biotechnology.
AB  - The van Deemter equation has been used to derive a rule of thumb guideline for
      scaling. The scaling is done by the concept of time scales. The time scales are
      kept identical for all the columns by scaling the flow rate to the total void
      volume and the load to the amount of the media. The verification of theoretical
      background for the linear gradient elution is reported. The results demonstrate
      that the gradient retention behaviour of protein is independent of the column
      aspect ratio, but it's a function of the initial salt concentration and the
      gradient slop G'.

PMID- 16581081
TI  - Purification of salvianolic acid B from the crude extract of Salvia miltiorrhiza
      with hydrophilic organic/salt-containing aqueous two-phase system by counter
      current chromatography.
AB  - Establishment of hydrophilic organic/salt-containing aqueous two-phase system and
      purification of salvianolic acid B from crude extract of S. miltiorrhiza by
      counter-current chromatography with said system were studied. Ethanol and n
      propanol were selected to constitute biphasic systems with ammonia sulphate,
      sodium chloride and phosphate separately, and related system characteristics
      including phase diagrams, phase ratio, separation time were tested. The partition
      coefficient of crude salvianolic acid B was also tested in above systems and
      further finely adjusted by altering the constitution of phosphate in n
      propanol/phosphate system. Salvianolic acid B was purified to 95.5% purity by
      counter-current chromatography in 36% (w/w) n-propanol/8% (w/w) phosphate system
      with the ratio between dipotassium hydrogen phosphate and sodium dihydrogen
      phosphate of 94:6. One hundred and eight milligrams of salvianolic acid B was
      purified from 285 mg crude extract with the recovery of 89%.

PMID- 16581082
TI  - Characterization of ceria-zirconia mixed oxides as catalysts for the combustion
      of volatile organic compounds using inverse gas chromatography.
AB  - Inverse gas chromatography (IGC) has been used in this work for characterizing
      the adsorption of different volatile organic compounds (VOCs) (1,2-dichloroethane
      (DCE), trichloroethylene (TCE), and n-hexane) over ceria-zirconia mixed oxides
      (Ce(x)Zr(1-x)O2, with x = 0, 0.15, 0.5, 0.68, 0.8 and 1). These materials have
      shown to be very active catalysts for the deep oxidation of the studied VOCs in
      previous papers. The enthalpies of adsorption (-deltaH(ads)), adsorption
      isotherms (corresponding to the Henry region), and dispersive (gamma(s)(D)) and
      specific (I(sp)) components of the surface energy for the adsorption of the
      investigated compounds are determined using IGC at infinite dilution. These
      chromatographic data and other surface parameters (surface area, oxygen storage
      capacity, surface acidity, and reducibility) are correlated with the activity and
      selectivity of these catalysts. As a result, for n-hexane, the catalytic activity
      is mainly correlated with the adsorption capacity of the solids, whereas the
      activity for chlorinated compounds oxidation (as well as the selectivity to
      oxidation products) depends on both oxygen storage capacity and specific
      interaction of the chlorinated compound with the surface.

PMID- 16581083
TI  - SiO2/Cr monolayers and formation of polyethylene films.
AB  - 1,3,5-tribenzylhexahydro-1,3,5-triazine-CrCl3 (TAC-CrCl3) was supported on
      monodisperse Stober silica and on commercial silica particles. The monolayers of
      these catalyst particles were successfully prepared with Langmuir-Blodgett
      technique. The effect of TAC-CrCl3 molecules on the ordering and film-forming of
      the silica particles was investigated. The particles arrange in domains of
      hexagonal ordering, but the ordering of particles in the monolayer decreases with
      increasing Cr loading. These hybrid monolayers are active polymerization
      catalysts. After polymerization, a relatively rough layer of polyethylene
      molecules covers the catalyst monolayer and this layer is hydrophobic. The
      monolayers and the polymers coating films were characterized by IR, UV-vis-NIR,
      and SEM. The method provides a way to fabricate polyethylene films on silica
      monolayers.

PMID- 16581084
TI  - Line of charges in electrolyte solution near a half-space I. Counterion
      condensation.
AB  - The effect of a half-space on counterion condensation around a line of charges in
      electrolyte solution is examined in the framework of Debye-Huckel electrostatics.
      The half-space substrate is allowed to be a conductor, a dielectric, or a
      semiconductor. Counterions are predicted to be released completely as the line of
      charges approaches a conducting substrate. When it approaches a dielectric
      substrate, depending on the ratio of solvent to substrate dielectric constant,
      there are three possibilities: (1) epsilon(sol)/epsilon(sub) < 1; the counterions
      are partially (or completely) released; (2) epsilon(sol)/epsilon(sub) = 1; the
      amount of condensation remains unchanged; and (3) epsilon(sol)/epsilon(sub) > 1;
      more counterions condense. Depending on the relative magnitude of screening
      lengths in the semiconductor and in the solution, its effect on condensation
      follows either that of a metal or that of a dielectric. For the case of a
      moderately doped silicon substrate, condensation is predicted to be similar to
      that for a dielectric.

PMID- 16581085
TI  - Adsorption of heavy metals on vermiculite: influence of pH and organic ligands.
AB  - The sorption behaviour of vermiculite has been studied with respect to cadmium,
      copper, lead, manganese, nickel, and zinc as a function of pH and in the presence
      of different ligands. The continuous column method was used in order to evaluate
      the feasibility to use the clay in wastewater purification systems. The total
      capacity of vermiculite was found to decrease in the following order: Mn > Ni >
      Zn > Cd > Cu > Pb. The adsorption of metal ions on vermiculite decreases with
      decreasing pH and increasing ionic strength. In general, the metal uptake on the
      clay was hindered by the presence of strong complexing agents in solution and it
      decreases with increasing of the complexation constants of the ligands with
      exception of cysteine and tiron. It is necessary, hence, to consider all these
      factors to effectively predict the uptake efficiency of this sorbent. However, it
      is possible to conclude that the vermiculite has good potentialities for cost
      effective treatments of metal-contaminated wastewaters.

PMID- 16581086
TI  - Transiently binding antibody fragments against Lewis x and sialyl-Lewis x.
AB  - Biomolecular recognition is often characterised by low affinity where many weak
      interactions work either alone or in concert, resulting in an inherent dynamic
      situation. For example the well-studied weak binding of cell-cell interactions is
      predominantly based on a range of carbohydrates that interact with numerous
      (protein) ligands. Finding appropriate binders to these carbohydrate structures
      may pave the way for new analytical strategies based on low affinity, and
      recombinant antibody technology is a promising approach to the development of
      such reagents. We have in the present study characterised two low affinity human
      single chain antibody fragments (scFv) by surface plasmon resonance for use in
      such applications. The two clones, LeX1 and sLeX10, had been selected from a
      naive phage display library against Lewis x (Le(x)) and sialyl Le(x) (sLe(x)),
      respectively. Both LeX1 and sLeX10 showed low affinity, with K(D) values of 3.5+/
      0.7 x 10(-5) M for Le(x) and 2.6+/-0.7 x 10(-5) M for sLe(x), respectively.
      Kinetic studies revealed the scFvs to be associated with fast dissociation rates,
      with Kd values higher than 0.1 s(-1) for both LeX1 and sLeX10. Apart from the
      Lewis structures Le(x) and sLe(x), we investigated the conformational isomers
      Lewis a and sialyl-Lewis a together with the monosaccharide units of the Lewis
      structures, and both scFvs showed high specificity for their respective
      carbohydrate. Taking these observations together we have demonstrated that scFv
      with fast reaction kinetics and low affinity have the necessary characteristics
      for further development as specific tools in analytical strategies, e.g.
      differentiation of cells based on the various configurations of carbohydrate
      epitopes.

PMID- 16581087
TI  - Long-term favorable response to interferon beta-1b is linked to cytokine
      deviation toward the Th2 and Tc2 sides in Japanese patients with multiple
      sclerosis.
AB  - To address the immune mechanism of the long-term beneficial effects of interferon
      beta (IFN-beta), we measured the intracellular cytokine production patterns of
      IFN-gamma, IL-4 and IL-13 in peripheral blood CD4+ and CD8+ T cells, which
      previously displayed alterations during the early course of IFN-beta treatment,
      in 15 Japanese patients after long-term IFN-beta administration. The patients
      were treated with IFN-beta-1b 8 x 10(6) units given subcutaneously every other
      day for a mean period of 34.5 +/- 5.5 months (range: 26-43 months). During the
      follow-up period, 6 patients experienced 33 relapses, while the other 9 were
      relapse-free. The results revealed the following cytokine alterations: (1) type 2
      cytokine, such as IL-4 and IL-13, were significantly increased in producing cell
      percentages in both CD4+ (p = 0.0356 and p = 0.0007, respectively) and CD8+ (p =
      0.0231 and p = 0.0170, respectively) T cells while IFN-gamma, a representative
      type 1 cytokine, was significantly decreased in the absolute producing cell
      numbers (p = 0.0125 in CD4+ T cells and p = 0.0022 in CD8+ T cells) even after
      approximately 3 years of IFN-beta administration; (2) the intracellular IFN-gamma
      / IL-4 ratio tended to decrease in both CD4+ and CD8+ T cells (p = 0.0535 and p =
      0.0783, respectively), reflecting a strong downmodulation of type 1 cytokine
      producing cells; and importantly (3) alterations such as the decreased
      intracellular IFN-gamma / IL-4 ratio in CD4+ T cells and increased percentage of
      CD8+ IL-13+ T cells compared with the pretreatment levels were only statistically
      significant in MS patients without relapse during IFN-beta therapy (p = 0.0152
      and p = 0.0078, respectively). Therefore, we consider that cytokine deviation
      toward the Th2 and Tc2 sides is linked to a long-term favorable response to IFN
      beta, while a higher intracellular IFN-gamma / IL-4 ratio is associated with
      treatment failure.

PMID- 16581088
TI  - Mutation of albedo and growth response produces oscillations in a spatial
      Daisyworld.
AB  - We extended a two-dimensional cellular automaton (CA) Daisyworld to include
      mutation of optimal growth temperature as well as mutation of albedo. Thus, the
      organisms (daisies) can adapt to prevailing environmental conditions or evolve to
      alter their environment. We find the resulting system oscillates with a period of
      hundreds of daisy generations. Weaker and less regular oscillations exist in
      previous daisyworld models, but they become much stronger and more regular here
      with mutation in the growth response. Despite the existence of a particular
      combination of mean albedo and optimum individual growth temperature which
      maximises growth, we find that this global state is unstable with respect to
      mutations which lower absolute growth rate, but increase marginal growth rate.
      The resulting system oscillates with a period that is found to decrease with
      increasing death rate, and to increase with increasing heat diffusion and heat
      capacity. We speculate that the origin of this oscillation is a Hopf bifurcation,
      previously predicted in a zero-dimensional system.

PMID- 16581089
TI  - Post-opioid receptor adaptations to chronic morphine; altered functionality and
      associations of signaling molecules.
AB  - Opioid desensitization/tolerance mechanisms have largely focused on adaptations
      that occur on the level of the mu-opioid receptor (MOR) itself. These include
      opioid receptor phosphorylation and ensuing trafficking events. Recent research,
      however, has revealed additional adaptations that occur downstream from the
      opioid receptor, which involve covalent modification of signaling molecules and
      altered associations among them. These include augmented isoform-specific
      synthesis of adenylyl cyclase (AC) and their phosphorylation as well as augmented
      phosphorylation of the G(beta) subunit of G(beta gamma). The aggregate effect of
      these changes is to shift mu-opioid receptor-coupled signaling from predominantly
      G(i alpha) inhibitory to (G(i)-derived) G(beta gamma) stimulatory AC signaling.
      Most recently, chronic morphine has been shown to enhance the association
      (interaction) between MOR and G(s), which should provide an additional avenue for
      offsetting inhibitory MOR signaling sequelae. The unfolding complexity of chronic
      morphine-induced sequelae demands an evolving broader and more encompassing
      perspective on opioid tolerance-producing mechanisms. This should facilitate
      understanding tolerance within the context of physiological plasticity that is
      activated by chronic exposure to drugs of abuse. Additional research is required
      to integrate the various tolerance-producing adaptations that have been
      elucidated to date. Specifically, the relative contribution to opioid tolerance
      of identified adaptations is still unknown as is the extent to which they vary
      among different regions of the central nervous system.

PMID- 16581090
TI  - Effects of U83836E on nerve functions, hyperalgesia and oxidative stress in
      experimental diabetic neuropathy.
AB  - Oxidative stress has been implicated to play an important role in the
      pathogenesis of diabetic neuropathy, which is the most common complication of
      diabetes mellitus affecting more than 50% of diabetic patients. In the present
      study, we have investigated the effect of U83836E [(-)-2-((4-(2,6-Di-1
      pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl)methyl)-3,4-dihydro-2,3,7,8-tetramethyl
      2H-1-benzopyran-6-ol, 2HCl], a potent free radical scavenger in streptozotocin
      (STZ)-induced diabetic neuropathy in rats. STZ-induced diabetic rats showed
      significant deficit in motor nerve conduction velocity (MNCV), nerve blood flow
      (NBF) and thermal hyperalgesia after 8 weeks of diabetes induction, indicating
      development of diabetic neuropathy. Antioxidant enzyme (superoxide dismutase and
      catalase) levels were reduced and malondialdehyde (MDA) levels were significantly
      increased in diabetic rats as compared to the age-matched control rats, this
      indicates the involvement of oxidative stress in diabetic neuropathy. The 2-week
      treatment with U83836E (3 and 9 mg/kg, i.p.) started 6 weeks after diabetes
      induction significantly ameliorated the alterations in MNCV, NBF, hyperalgesia,
      MDA levels and antioxidant enzymes in diabetic rats. Results of the present study
      suggest the potential of U83836E in treatment of diabetic neuropathy.

PMID- 16581091
TI  - Mechanisms of human minisatellite mutation in yeast.
AB  - Minisatellites are tandem repeat loci, with repeat units ranging in size from 5
      bp to 100 bp. The total lengths of repeat arrays vary from about 0.5 kb to 30 kb,
      and excessive variability in allele length at human minisatellite loci is the
      result of germline-specific complex recombination events generating new length
      alleles. Minisatellite alleles also mutate to new lengths in somatic cells, but
      this occurs at a much lower rate than in the germline. Since recombination is
      involved in minisatellite mutation, the yeast Saccharomyces cerevisiae is a
      suitable model organism that has been employed to further dissect the molecular
      basis of mutation events at human minisatellites. These studies have shown that
      the mutational behaviour of a minisatellite in meiosis is not determined by the
      intrinsic properties of the repeat array, but are highly dependent on the
      position of the minisatellite in the genome. The processes for minisatellite
      mutation in yeast and humans are identical in the sense that mutation is indeed
      driven by meiotic recombination, but differ with regard to the types of
      structural changes that are generated by the recombination events. Tetrad
      analyses showed that inter-allelic transfers of repeats occur by conversion and
      not crossing over, and that several chromatids can be involved in successive
      recombination events in one meiosis, resulting in mutant alleles in several
      spores. It has been demonstrated that the genes SPO11 and RAD50, involved in the
      initiation of recombination events, are required for human minisatellite mutation
      in yeast meiosis. Intrinsic properties of the repeat array appear to determine
      the stability of human minisatellites in yeast mitosis, since mitotic mutation
      rates in yeast are highly variable between minisatellites. The repair genes RAD27
      and DNA2 stabilise human minisatellites in yeast mitosis, while RAD5 has no
      effect on mitotic stability. MSH2 depresses human minisatellite frequency in
      meiotic cells of yeast.

PMID- 16581092
TI  - Characterisation of the selective 5-HT1B receptor antagonist SB-616234-A (1-[6
      (cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2'-methyl-4'
      (5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride): in vivo
      neurochemical and behavioural evidence of anxiolytic/antidepressant activity.
AB  - The 5-HT1B receptor has attracted significant interest as a potential target for
      the development of therapeutics for the treatment of affective disorders such as
      anxiety and depression. Here we present the in vivo characterisation of a novel,
      selective and orally bioavailable 5-HT1B receptor antagonist, SB-616234-A (1-[6
      (cis-3,5-dimethylpiperazin-1-yl)-2,3-dihydro-5-methoxyindol-1-yl]-1-[2'-methyl-4'
      (5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methanone hydrochloride). SB-616234
      A reversed the 5-HT1/7 receptor agonist, SKF-99101H-induced hypothermia in guinea
      pigs in a dose related manner with an ED50 of 2.4 mg/kg p.o. Using in vivo
      microdialysis in freely moving guinea pigs, SB-616234-A (3-30 mg/kg p.o.) caused
      a dose-related increase in extracellular 5-HT in the dentate gyrus. Evaluation of
      antidepressant- and anxiolytic-like effects of this 5-HT1B receptor antagonist
      was performed in a variety of models and species. SB-616234-A produced a decrease
      in immobility time in the mouse forced swim test; an effect suggestive of
      antidepressant activity. Furthermore, SB-616234-A produced dose-related
      anxiolytic effects in both rat and guinea pig maternal separation-induced
      vocalisation models with an ED50 of 1.0 and 3.3 mg/kg i.p., respectively (vs
      fluoxetine treatment ED50 = 2.2 mg/kg i.p. in both species). Also a significant
      reduction in posturing behaviours was observed in the human threat test in
      marmosets; an effect indicative of anxiolytic activity. In summary, SB-616234-A
      is a novel, potent and orally bioavailable 5-HT1B receptor antagonist which
      exhibits a neurochemical and behavioural profile that is consistent with both
      anxiolytic- and antidepressant-like activity in a variety of species. Taken
      together these data suggest that SB-616234-A may have therapeutic efficacy in the
      treatment of affective disorders.

PMID- 16581094
TI  - How automatic are audiovisual links in exogenous spatial attention?
AB  - Three experiments on healthy humans investigated the degree of automaticity of
      crossmodal spatial attention shifts by assessing the intentionality criterion. We
      used the orthogonal cuing paradigm in which a lateralized cue, either visual or
      auditory was followed by a unimodal or crossmodal target that occurred at the
      same or opposite side. In all experiments, the cue was always uninformative as to
      target location. In Experiment 1, where both side and modality of targets were
      unpredictable, we found faster discriminations for visual targets following
      uninformative auditory cues on the same side. This result was replicated in
      Experiment 2, where target side was blocked and participants could orient
      attention in advance toward the appropriate side, and in Experiment 3, where they
      were additionally informed about target modality. Our results suggest that this
      sort of crossmodal orienting is automatic because it occurred even when
      participants were provided with detailed information about the target to prevent
      uninformative auditory cues from orienting attention. This is consistent with the
      notion that peripheral auditory stimuli are very powerful in capturing visual
      attention.

PMID- 16581093
TI  - Differential pharmacological in vitro properties of organic cation transporters
      and regional distribution in rat brain.
AB  - Organic cation transporters (OCTs) are polyspecific carriers implicated in low
      affinity, corticosteroid-sensitive extraneuronal catecholamine uptake in
      peripheral tissues. The three main OCT subtypes, OCT1, OCT2 and OCT3, are also
      present in the brain, but their central role remains unclear. In the present
      study, we investigated by comparative in situ hybridization analysis the regional
      distribution of these transporters in rat brain and compared their functional
      properties in stably transfected HEK293 cells expressing human or rat OCTs. In
      rat brain, OCT2 and OCT3 mRNAs are expressed predominantly in regions located at
      the brain-cerebrospinal fluid border, with OCT3 mRNA expression extending to
      regions that belong to monoaminergic pathways such as raphe nuclei, striatum and
      thalamus. After normalization with MPP+ uptake, OCT2 and OCT3 subtypes share a
      similar monoamine preference profile, with higher transport efficacies for
      epinephrine and histamine than for the other monoamines. Interestingly, a
      significant level of epinephrine transport, previously only shown for rOCT2, is
      achieved by most OCTs subtypes. Finally, another novel finding was that OCTs are
      sensitive to 3,4-methylenedioxymetamphetamine (MDMA), phencyclidine (PCP), MK-801
      and ketamine. Altogether, all our results suggest a functional specialization of
      OCT subtypes, based both on their intrinsic properties and their differential
      regional expression pattern in the brain.

PMID- 16581095
TI  - Asymmetrical perception of body rotation after unilateral injury to human
      vestibular cortex.
AB  - Vestibular information plays a key role in many perceptual and cognitive
      functions, but surprisingly little is known about how vestibular signals are
      processed at the cortical level in humans. To address this issue, we tested the
      ability of two patients, with damage to key components of the vestibular network
      in either the left or right hemisphere, to perceive passive whole-body rotations
      (25-125 degrees) about the yaw axis. In both patients, the posterior insula,
      hippocampus, putamen, and thalamus were extensively damaged. The patients'
      responses were compared with those of nine age- and sex-matched neurologically
      intact participants. The body rotations were conducted without vision and the
      peak angular velocities ranged from 40 degrees to 90 degrees per second.
      Perceived rotation was assessed by open-loop manual pointing. The right
      hemisphere patient exhibited poor sensitivity for body rotations toward the
      contralesional (left) hemispace and generally underestimated the rotations. By
      contrast, his judgments of rotations toward the ipsilesional (right) hemispace
      greatly overestimated the physical rotation by 50-70 degrees for all tested
      magnitudes. The left hemisphere patient's responses were more appropriately
      scaled for both rotation directions, falling in the low-normal range. These
      findings suggest that there is some degree of hemispheric specialization in the
      cortical processing of dynamic head rotations in the yaw plane. In this view,
      right hemisphere structures play a dominant role, processing rotations in both
      directions, while left hemisphere structures process rotations only toward the
      contralesional hemispace.

PMID- 16581096
TI  - Adaptation of healthy mastication to factors pertaining to the individual or to
      the food.
AB  - Mastication is a physiological process controlled by the central nervous system
      and modulated by inputs from the mouth. Both the intrinsic characteristics of the
      subject and the extrinsic characteristics of the chewed food are responsible for
      variations of the masticatory function. Age, gender and dental state constitute
      the most studied intrinsic factors whereas hardness, rheological characteristics
      such as plasticity or elasticity, and food size are the better known extrinsic
      factors. These factors cause physiological adaptations which can occur during
      individual cycles or the whole sequence of mastication. Electromyographic and jaw
      movements (kinematic) recordings are commonly used to study mastication, from
      which, several variables can be measured. Vertical and lateral amplitudes and,
      velocities of jaw movements, are only given by kinematic recordings.
      Bioelectrical activities per cycle or per sequence are closely linked to
      masticatory forces and are measured from electromyographic recordings. Number of
      cycles, sequence duration and masticatory frequency can be measured from both
      types of recordings. The objective of this review is to provide an overview of
      the variations of the measured masticatory variables that occur when mastication
      adapts to changes in characteristics of the individual or the food.

PMID- 16581097
TI  - A 2D spring model for the simulation of ultrasonic wave propagation in nonlinear
      hysteretic media.
AB  - A two-dimensional (2D) approach to the simulation of ultrasonic wave propagation
      in nonclassical nonlinear (NCNL) media is presented. The approach represents the
      extension to 2D of a previously proposed one dimensional (1D) Spring Model, with
      the inclusion of a PM space treatment of the intersticial regions between grains.
      The extension to 2D is of great practical relevance for its potential
      applications in the field of quantitative nondestructive evaluation and material
      characterization, but it is also useful, from a theoretical point of view, to
      gain a better insight of the interaction mechanisms involved. The model is tested
      by means of virtual 2D experiments. The expected NCNL behaviors are qualitatively
      well reproduced.

PMID- 16581098
TI  - Destruction of formic acid using high frequency cup horn reactor.
AB  - Degradation of formic acid has been studied in a high frequency cup horn type
      reactor with an aim of understanding the effect of operating parameters on the
      destruction efficiency. The methodology used in the work serves as a useful
      guideline for the optimization exercise for the sonochemical reactors to
      establish a set of operating parameters at large scale operation for achieving
      maximum efficiency. Firstly energy efficiency of the reactor has been established
      as a function of the operating volume with an aim of optimization of the capacity
      of the reactor for maximum extent of degradation. It has been observed that
      maximum transfer of supplied power is obtained at 300 ml capacity and hence the
      actual degradation studies have been performed with this operational capacity.
      The effect of time of irradiation, initial concentration of the pollutant,
      stirrer speed, presence of sodium sulfite (to scavenge the initial dissolved
      oxygen) on the extent of degradation has been investigated. Maximum extent of
      degradation has been observed under the conditions of 500 mg/l initial
      concentration, 200 rpm stirrer speed and presence of initial dissolved oxygen (no
      sodium sulfite in the system). Process intensification studies have been carried
      out using sodium chloride over a range of initial concentration and it has been
      observed that maximum extent of degradation of formic acid is obtained at 4% NaCl
      concentration. Comparison has been also made with different sonochemical
      configurations operating at lower frequency of irradiation (typically in the
      range of 20-50 kHz) with an aim of comparing the efficacies of the reactor at
      equivalent power consumption.

PMID- 16581099
TI  - Effects of medetomidine, a novel antifouling agent, on the burrowing bivalve Abra
      nitida (Muller).
AB  - The effects of medetomidine, a novel antifouling candidate, on the burrowing
      bivalve Abra nitida were studied. The burrowing behaviour, sediment reworking
      activity and faeces production were assessed after 24 h exposure of A. nitida to
      sublethal concentrations of medetomidine. Medetomidine caused a significant
      decrease in the burrowing response and in the sediment reworking activity. The
      median effective concentrations (EC50) were 430 nM (86 microg/l) and 4.4 nM (0.9
      microg/l), respectively. No effects on the faeces production were detected.
      Although significant effects of medetomidine on A. nitida were registered, a
      reversibility of the effects was observed when 24 h-exposed animals were
      incubated in clean seawater and sediment for 24 h. Considerations relating to the
      future commercialisation of medetomidine for antifouling purposes are discussed.

PMID- 16581100
TI  - Physical and chemical regeneration of zeolitic adsorbents for dye removal in
      wastewater treatment.
AB  - Natural zeolite and synthetic zeolite, MCM-22, were employed as effective
      adsorbents for a basic dye, methylene blue, removal from wastewater. Two methods,
      Fenton oxidation and high temperature combustion, have been used for regeneration
      of used materials. It is found that MCM-22 exhibits equilibrium adsorption at 1.7
      x 10(-4) mol g(-1), much higher than the adsorption of natural zeolite (5 x 10(
      5) mol g(-1)) at initial dye concentration of 2.7 x 10(-5)M and 30 degrees C.
      Solution pH will affect the adsorption behaviour of MCM-22. Higher solution pH
      results in higher adsorption capacity. The regenerated adsorbents show different
      capacity depending on regeneration technique. Physical regeneration by high
      temperature combustion will be better than chemical regeneration using Fenton
      oxidation in producing effective adsorbents. Regeneration of MCM-22 by high
      temperature treatment can make the adsorbent exhibit comparable or superior
      adsorption capacity as compared to the fresh sample depending on the temperature
      and time. The optimal temperature and time will be 540 degrees C and 1h. The
      Fenton oxidation will recover 60% adsorption capacity. For natural zeolite,
      regeneration can not fully recover the adsorption capacity with the two
      techniques and the regenerated natural zeolites by the two techniques are
      similar, showing 60% adsorption capacity of fresh sample. Kinetic studies
      indicate that the adsorption follows pseudo-second-order kinetics.

PMID- 16581101
TI  - Characterization of surface marine sediments from Ria de Arousa estuary according
      to extractable humic matter content.
AB  - Surface marine sediments from Ria de Arousa estuary were analyzed for humic and
      fulvic acids by UV-visible spectrometry and have been characterized using
      elemental analysis (carbon, hydrogen and nitrogen elemental composition) and
      spectrometric data (A2/A4 ratio, absorbancies at 270 and 407 nm and E4/E6 ratio,
      absorbancies at 465 and 665 nm). These variables have been used as discriminating
      factors to distinguish of marine and terrestrial origin of humic and fulvic acids
      in Ria de Arousa surface marine sediments. Principal component analysis, PCA, and
      cluster analysis, CA, have been used as unsupervised pattern recognition
      procedures. The half-range central value transformation was used as data pre
      treatment to homogenize data. After a Varimax rotation, PCA applied to humic acid
      data has reveled that spectrometric A2/A4 and E4/E6 ratios are the main
      dominating features in the first principal component (48.6% of total variance),
      the humic acid content is the feature with the highest weight in the second
      principal component (22.9% of the total variability) and the carbon elemental
      composition domain in the third principal component (13.3% of total variance).
      Results from PCA have revealed that surface sediments collected at inner-left
      part of the estuary and at the mouth of the river Ulla belong to the same group.
      Similarly, PCA has shown that surface sediments from the right mouth of the
      estuary form a compact group. Taking in account the water circulation in Ria de
      Arousa estuary, these findings mean that the organic matter in surface sediments
      from the inner-left part of the estuary derived mainly from terrestrial organic
      matter while the organic matter in surface sediments from the right mouth of the
      estuary is mainly derived from marine sources. Finally, it must be noticed that
      any classification of surface sediments was assessed when applying of PCA and CA
      from fulvic acids data.

PMID- 16581102
TI  - NO removal by reducing agents and additives in the selective non-catalytic
      reduction (SNCR) process.
AB  - The effect of the additives on the selective non-catalytic reduction (SNCR)
      reaction has been determined in a three-stage laboratory scale reactor. The
      optimum reaction temperature is lowered and the reaction temperature window is
      widened with increasing concentrations of the gas additives (CO, CH4). The
      optimum reaction temperature is lowered and the maximum NO removal efficiency
      decreases with increasing the concentration of alcohol additives (CH3OH, C2H5OH).
      The addition of phenol lowers the optimum reaction temperature about 100-150
      degrees C similar to that of the toluene addition. The volatile organic compounds
      (VOCs: C6H5OH, C7H8) can be utilized in the SNCR process to enhance NO reduction
      and removed at the same time. A previously proposed simple kinetic model can
      successfully apply the NO reduction by NH3 and the present additives.

PMID- 16581103
TI  - Analysing selected VVOCs in indoor air with solid phase microextraction (SPME): a
      case study.
AB  - A multi-storey building with great diversity of room use was monitored after
      extensive renovation to remove mould growth secondary to a leaky roof. Tests for
      volatile organic compounds (VOC) with activated charcoal showed a successfully
      renovation. Solid phase microextraction (SPME) for detection of selected very
      volatile organic compounds (VVOCs) revealed indoor air concentrations ranging
      from 550 to 4,600 microg m(-3). The SPME technique also successfully detected
      emissions from working and building materials and documented the results of
      remedial measures in offices. The prior and current use of acetone, methyl
      acetate and 2-methylpentane within the building resulted in their elevated
      concentrations in other building floors.

PMID- 16581104
TI  - Effects of lead contamination on soil microbial activity and rice physiological
      indices in soil-Pb-rice (Oryza sativa L.) system.
AB  - The effect of lead (Pb) treatment on the soil microbial activities (soil
      microbial biomass and soil basal respiration) and rice physiological indices were
      studied by greenhouse pot experiment. Pb was applied as lead acetate at six
      different levels in two different paddy soils, namely 0 (control), 100, 300, 500,
      700, 900 mg kg-1 soil. The results showed that the application of Pb at lower
      level (<300 mg kg-1) as lead acetate resulted in a slight increase in soil
      microbial activities compared with the control, and had an inhibitory influence
      at high concentration (>500 mg Pb kg-1 soil), which might be the critical
      concentration of Pb causing a significant decline in the soil microbial
      activities. However, the degree of influence on soil microbial activities by Pb
      was related to the clay and organic matter contents of the soils. On the other
      hand, when the level of Pb treatments increased to 500 mg kg-1, there was
      ecological risk for both soil microbial activities and plants. The results also
      revealed that there was a consistent trend that the chlorophyll contents
      increased initially, and then decreased gradually with increase in Pb
      concentration. Pb was effective in inducing proline accumulation and its toxicity
      causes oxidative stress in rice plants. In a word, soil microbial activities and
      rice physiological indices, therefore, may be sensitive indicators reflecting
      environmental stress in soil-Pb-rice system.

PMID- 16581105
TI  - Analysis of bioavailable phenols from natural samples by recombinant luminescent
      bacterial sensors.
AB  - A whole-cell recombinant bacterial sensor for the detection of phenolic compounds
      was constructed and used for the analysis of bioavailable phenols in natural
      samples. The sensor Pseudomonas fluorescens OS8(pDNdmpRlux) contains luxCDABE
      operon as a reporter under the control of phenol-inducible Po promoter from
      Pseudomonas sp. CF600. Expression of lux genes from the Po promoter, and thus the
      production of bioluminescence is controlled by the transcriptional activator
      DmpR, which initiates transcription in the presence of phenolic compounds. To
      take into account possible quenching (turbidity, toxicity) and/or stimulating
      effects of the environmental samples on the bacterial luminescence, control
      bacteria comparable to the sensors but lacking the phenol recognising elements
      were constructed and used in parallel in assays. The sensor bacteria were
      inducible with phenol, methylphenols, 2,3-, 2,4-, 2,6- and 3,4-dimethylphenol,
      resorcinol and 5-methylresorcinol but not with 2,5-dimethylresorcinol. The
      detection limits for different phenols varied from 0.03 mg/l (2-methylphenol) to
      42.7 mg/l (5-methylresorcinol), being 0.08 mg/l for phenol, the most abundant
      phenolic contaminant in the environment. Different phenolic compounds had an
      additive effect on the inducibility of the sensor. The constructed sensor
      bacteria were applied on groundwaters and semi-coke leachates to estimate the
      bioavailable fraction of phenols. The sensor-determined amount of phenols in
      different samples varied from 6% to 95% of total phenol content depending on the
      nature of the sample. As the phenol-recognising unit in the sensor originates
      from a natural phenol biodegradation pathway, the sensor-determined amount of
      phenols corresponds to the biodegradable amount of phenolic pollutants in the
      samples and therefore this sensor could be used to estimate the natural
      biodegradation potential of phenolic compounds in the complex environmental
      mixtures and matrixes.

PMID- 16581107
TI  - Effect of oxygen limitation on solid-bed bioleaching of heavy metals from
      contaminated sediments.
AB  - The effects of oxygen limitation on solid-bed bioleaching of heavy metals (Me)
      were studied in a laboratory percolator system using contaminated sediment
      supplemented with 2% elemental sulfur (So). Oxygen limitation was realized by
      controlling the gas flow and oxygen concentration in the aeration gas. The oxygen
      supply varied between 150 and 0.5 mol So (-1) over 28 d of leaching. Moderate
      oxygen limitation led to temporarily suppression of acidification, rate of
      sulfate generation and Me solubilization. Lowering the oxygen supply to 0.5 mol
      O2 mol So (-1) resulted in retarding acidification over a period of three weeks
      and in poor Me solubilization. Oxidation of So occurred even under strong oxygen
      limitation at a low rate. High surplus of oxygen was necessary for almost
      complete oxidation of the added So. The maximum Me solubilization was reached at
      an oxygen supply of 7.5 mol O2 mol So (-1). Thus, the oxygen input during solid
      bed bioleaching can be reduced considerably by controlling the gas flow without
      loss of metal removal efficiency. Oxygen consumption rates, ranging from 0.4 x
      10(-8) to 0.8 x 10(-8) Kg O2 Kg dm (-1) S(-1), are primarily attributed to high
      reactivity of the sulfur flower and high tolerance of indigenous autotrophic
      bacteria to low oxygen concentrations. The So related oxygen consumption was
      calculated assuming a molar yield coefficient Y O2/S of 1.21. The oxygen
      conversion degree, defined as part of oxygen feed consumed by So oxidation,
      increased from 0.7% to 68% when the oxygen supply was reduced from 150 to 0.5 mol
      O2 mol So (-1).

PMID- 16581106
TI  - Plant-accelerated dissipation of phenanthrene and pyrene from water in the
      presence of a nonionic-surfactant.
AB  - Plant-accelerated dissipation of phenanthrene and pyrene in water in the presence
      of a nonionic-surfactant (Brij35) was studied. The mechanisms involved were
      evaluated, based on the investigation of plant uptake of these compounds from
      water with Brij35. The presence of ryegrass (Lolium multiflorum Lam) clearly
      enhanced the dissipation of tested PAHs in water with 0-296 mg l(-1) Brij35. The
      first-order rate constants (K), calculated from the first-order kinetic models
      for these PAH degradation (all significant at P < 0.05, n=8), of phenanthrene and
      pyrene in the presence of ryegrass were 16.7-50% and 47.1-108% larger than those
      of plant-free treatments, whereas half-lives (T1/2) of the former were 14.3-33.4%
      and 32.0-52.0% smaller than the latter, respectively. However, the promotion of
      PAH dissipation by ryegrass was found to significantly decrease with increasing
      Brij35 concentrations. In the range of 0-296 mg l(-1), low concentrations (< or =
      74.0 mg l(-1)) of Brij35 generally enhanced plant uptake and accumulation of
      phenanthrene and pyrene, based on the observed plant concentrations and
      accumulated amounts of these chemicals from water. In contrast, Brij35 at
      relatively high concentrations (> or = 148 mg l(-1)) markedly restricted plant
      uptake of these PAHs. Plant accumulation of phenanthrene and pyrene accounted for
      6.21-35.0% and 7.66-24.3% of the dissipation enhancement of these compounds from
      planted versus unplanted water bodies. In addition, plant metabolism was
      speculated to be another major mechanism of plant-accelerated dissipation of
      these PAHs in water systems. Results obtained from this study provided some
      insight with regard to the feasibility of phytoremediation for PAH contaminated
      water bodies with coexisted contaminants of surfactants.

PMID- 16581108
TI  - Application of ozone, UV and ozone/UV processes to reduce diethyl phthalate and
      its estrogenic activity.
AB  - A research study to monitor the micropollutant levels present in the Han River, a
      major drinking water source for the Seoul Metropolitan district in Korea, was
      performed over a five-year period from 2000 to 2004, inclusive. Of the detected
      micropollutants, phthalates were found to be the major contaminants. In this
      study, the estrogenic activities of the detected phthalates and raw water samples
      contaminated with the pollutants were assessed by the E-screen assay using the
      MCF-7 breast cancer cell line. Of the phthalates, diethyl phthalate (DEP) and
      di(2-ethylhexyl) phthalate (DEHP) showed relatively high cell proliferation.
      Using DEP as a phthalate probe, three candidate processes, ozone alone, UV alone,
      and the ozone/UV combined, were evaluated for their efficiency in removing DEP
      and reducing its estrogenic activity. The ozone/UV process was shown to have the
      highest efficiency for the elimination of DEP and its by-products, leading to the
      complete mineralization of DEP. This study also found that the ozone/UV process
      is the best candidate to reduce the estrogenicity induced by DEP and its by
      products.

PMID- 16581109
TI  - Trace element availability and plant growth in a mine-spill contaminated soil
      under assisted natural remediation I. Soils.
AB  - We evaluated the effects of different amendments and/or a plant cover on
      reclamation of a trace element contaminated soil. Seven treatments were
      established: four organic (leonardite (LEO), litter (LIT), municipal waste
      compost (MWC), biosolid compost (BC)), one inorganic (sugar beet lime (SL)) and
      two controls (control without amendment but with Agrostis (CTRP) and control
      without amendment and without Agrostis (CTR)). Results showed that total organic
      C was significantly higher in organic treatments in all samplings. Water-soluble
      C was lower in CTR compared to other treatments, but no significant differences
      were observed between organic treatments and SL and CTR. SL, BC and MWC
      treatments increased soil pH and reduced 0.01 M CaCl2-extractable Cd, Cu and Zn
      concentrations more efficiently, especially in the first 2 years. At the end of
      the experiment 0.01 M CaCl2-extractable trace element concentrations were similar
      in all treatments. 0.01 M CaCl2-extractable As and Pb were below the detection
      limit. Addition of amendments showed no clear reduction in 0.05 M EDTA
      extractable trace element concentrations and some amendments even increased 0.05
      M EDTA-extractable As and Cu with time. Pseudo-total trace element concentrations
      were higher for As in controls. On the other hand, mean values of Cu and Zn were
      higher in MWC treatment. BC and SL treatments also showed higher Zn mean
      concentration than controls. No amendment effect was observed for Cd and Pb.

PMID- 16581110
TI  - Loggerhead sea turtle (Caretta caretta) egg yolk concentrations of persistent
      organic pollutants and lipid increase during the last stage of embryonic
      development.
AB  - Data are scarce describing the concentrations of polychlorinated biphenyls (PCBs)
      and organochlorine pesticides in sea turtle eggs. The purpose of this study was
      to establish appropriate sample collection methodology to monitor these
      contaminants in sea turtle eggs. Contaminant concentrations were measured in yolk
      samples from eggs that failed to hatch from three loggerhead sea turtle (Caretta
      caretta) nests collected in southern Florida to determine if concentrations
      change through embryonic development. One to three egg yolk samples per nest were
      analyzed from early, middle, and late developmental stages (n=22 eggs total). PCB
      and pesticide concentrations were determined by gas chromatography with electron
      capture detection (GC-ECD). Geometric mean concentrations of summation
      operatorPCBs (52 congeners), summation operatorDDTs, summation
      operatorchlordanes, and dieldrin in all eggs were 65.0 (range=7.11 to 3930 ng/g
      lipid), 67.1 (range=7.88 to 1340 ng/g lipid), 37.0 (range=4.04 to 685 ng/g
      lipid), and 11.1 ng/g lipid (range=1.69 to 44.0 ng/g lipid), respectively. Early
      and middle developmental stage samples had similar concentrations of PCBs and
      organochlorine pesticides on a wet-mass basis (ng/g tissue extracted), but the
      concentrations doubled by the late stage. This increase is most likely
      attributable to the 50% increase in lipid content observed in the late-stage
      yolk. These findings indicate that an early-stage sample cannot be directly
      compared to a late-stage sample, especially from different nests. These
      preliminary findings also allowed us to calculate the minimum number of eggs per
      nest required for analysis to obtain an acceptable mean concentration per nest.
      More research is required to investigate geographical trends of contaminant
      concentrations and potential health effects (i.e., abnormalities) caused by these
      contaminants on sea turtle development.

PMID- 16581112
TI  - Corporeal excavation: new technique for penile prosthesis implantation in men
      with severe corporeal fibrosis.
AB  - INTRODUCTION: Penile prosthesis implantation in men who have fibrotic corpora as
      the result of ischemic priapism or previous removal of an infected penile
      prosthesis poses a significant challenge to the implanting surgeon. We describe a
      new technique, corporeal excavation, to meet this challenge. TECHNICAL
      CONSIDERATIONS: The operative approach is through an inverted T penoscrotal
      incision that affords exposure of nearly the entire corpus cavernosum on each
      side. Extended corporotomies are made on the ventral aspect of each corpus
      cavernosum, and a plane of dissection between the fibrotic corporeal tissue and
      the inner surface of the tunica albuginea is established, resulting in core
      removal of nearly all fibrotic intracorporeal tissue. Cylinders are laid into the
      empty corporeal bed, and the tunica albuginea is closed primarily. Nine patients
      were identified who had undergone this procedure. The operative notes and medical
      records were reviewed, and telephone interviews were done for follow-up when
      patients had not been recently seen in the clinic. CONCLUSIONS: Successful
      outcomes were achieved in all 9 patients. Corporeal excavation permits penile
      prosthesis implantation in men with severe intracorporeal fibrosis usually
      resulting from priapism or previous removal of infected penile prostheses.

PMID- 16581111
TI  - Genetic polymorphisms of the platelet receptors P2Y(12), P2Y(1) and GP IIIa and
      response to aspirin and clopidogrel.
AB  - INTRODUCTION: There is wide variability in the responses of individual patients
      to aspirin and clopidogrel. Polymorphisms of several platelet receptors have been
      related to increased platelet aggregation. We therefore aimed to evaluate whether
      these polymorphisms are related to altered response to aspirin or clopidogrel.
      MATERIALS AND METHODS: Patients (n=120) undergoing percutaneous coronary
      intervention who received aspirin for > or =1 week but not clopidogrel were
      included. Blood samples were drawn at baseline and 20-24h after a 300-mg
      clopidogrel dose. Aspirin insensitivity was defined as 5 microM ADP-induced
      aggregation > or =70% and 0.5 mg/mL arachidonic acid-induced aggregation > or
      =20%. Clopidogrel insensitivity was defined as baseline minus post-treatment
      aggregation < or =10% in response to 5 and 20 microM ADP. PlA polymorphism of
      glycoprotein IIIa, T744C polymorphism of the P2Y(12) gene and the 1622A>G
      polymorphism of the P2Y(1) gene were genotyped by polymerase chain reaction.
      RESULTS: There were no differences in polymorphism frequencies between drug
      insensitive vs. drug-sensitive patients. There were also no significant
      differences in response to aspirin (assessed by arachidonic acid-induced
      aggregation) or to clopidogrel (assessed by ADP-induced aggregation or activation
      markers) when patients were grouped according to genotype. The only trend
      observed was lower reduction in PAC-1 binding following clopidogrel in PlA(2)
      carriers (P=0.065). CONCLUSIONS: We did not find an association between
      polymorphisms in the platelet receptors GP IIIa, P2Y(12) or P2Y(1) and response
      to aspirin or clopidogrel in cardiac patients. These findings suggest that the
      variability in response to anti-platelet drugs is multi-factorial and is not
      caused only by single gene mutations.

PMID- 16581113
TI  - Effect of intralesional interferon-alpha 2b combined with oral vitamin E for
      treatment of early stage Peyronie's disease: a randomized and prospective study.
AB  - OBJECTIVES: To compare the efficacy and safety of intralesional interferon-alpha
      2b combined with oral vitamin E or intralesional interferon-alpha 2b alone or
      oral vitamin E alone for the treatment of Peyronie's disease. METHODS: From
      January 2000 to March 2002, a total of 30 consecutive men with Peyronie's disease
      were randomized prospectively into three different treatment groups. All the
      patients were assessed objectively with penile duplex Doppler ultrasonography for
      plaque size, location, and presence of calcification before and after treatment.
      Subjective data were obtained by querying about the improvement in penile pain
      and by using the "global efficacy question" for the assessment of the quality of
      sexual intercourse at the end of the study. A total of 5.0 x 10(6) U of
      interferon-alpha 2b was given once per week directly into the plaque for a period
      of 12 weeks. Patients received 400 IU of vitamin E orally twice daily for 6
      months. RESULTS: At the 6-month follow-up visit, we did not find any
      statistically significant changes in the objective parameters when compared with
      the initial findings in each group or among the three groups (P >0.05). We did
      not observe any clinically significant improvement in the subjective parameters
      among the three groups (P >0.05). However, all patients who were treated with
      interferon-alpha 2b experienced brief flu-like side effects. CONCLUSIONS: Our
      findings indicate that 5 million units of intralesional interferon-alpha 2b
      injection therapy either alone or in combination with vitamin E does not appear
      to be clinically effective in the management of early stage Peyronie's disease
      compared with only oral vitamin E.

PMID- 16581114
TI  - Simultaneous double adult kidney transplantation using single arterial and venous
      anastomoses.
AB  - INTRODUCTION: To provide optimal nephron mass, two adult kidneys can be
      transplanted into a single recipient. TECHNICAL CONSIDERATIONS: All techniques
      described to date have been based on the sequential transplantation of each
      transplant in a separate iliac fossa. We report on an operative technique
      allowing the simultaneous transplantation of both kidneys into the same iliac
      fossa, with simultaneous revascularization through a single arterial and single
      venous anastomosis in 12 patients. CONCLUSIONS: This technique reduces the
      surgical dissection, anesthesia exposure, and risk to elderly recipients and can
      be added to the armamentarium of the transplant surgeon.

PMID- 16581115
TI  - Effect of bupropion on physiological measures of stress in smokers during
      nicotine withdrawal.
AB  - Studies suggest that among cigarette smokers trying to quit, stress undermines
      abstinence. Little research has assessed if therapies that increase smoking
      cessation rates impact physiological measures of stress response. Forty-three
      subjects completed this repeated-measures study in which a laboratory assessment
      was completed at baseline and after 17 days of treatment with either placebo
      (n=15), bupropion sustained release (150 mg twice daily) (n=14) or bupropion with
      stress reduction counseling (n=14). All subjects quit smoking 3 days prior to the
      second laboratory assessment. At each laboratory assessment physiological
      measures of stress (i.e. blood pressure, heart rate, plasma epinephrine,
      norepinephrine and cortisol concentrations) were measured during rest periods and
      in response to a speech, a math and a cold pressor task. Among subjects taking
      placebo, physiological measures of stress were generally lower at rest and during
      the stressors after smoking cessation. In those taking bupropion these measures
      were equivalent at the two assessments. Additionally, compared to placebo, those
      on bupropion had a greater diastolic blood pressure response to the speech
      stressor and greater systolic blood pressure response to the math stressor during
      the second laboratory session. This study suggests that bupropion may be
      maintaining physiological measures of stress during the nicotine withdrawal
      period.

PMID- 16581116
TI  - Effects of dexamethasone treatment (to mimic stress) and Vitamin E oral
      supplementation on the spermiogram and on seminal plasma spontaneous lipid
      peroxidation and antioxidant enzyme activities in dogs.
AB  - The objective was to determine if treatment with dexamethasone (to mimic stress)
      has a deleterious effect on the spermiogram and on the composition of seminal
      plasma in the dog and whether adverse effects were reduced by oral
      supplementation with Vitamin E. Eighteen adult male Rottweiler dogs were randomly
      allocated in a 2 x 2 factorial treatment design (with or without dexamethasone
      treatment versus with or without Vitamin E supplementation). Dogs in the
      supplemented group received 500 mg of alpha-tocopherol (Vitamin E)/dog/day per os
      for 10 weeks. Dexamethasone (0.01 mg/kg/day i.m.) was given once daily for 7
      days, starting 7 days after the onset of Vitamin E supplementation. Food intake,
      body condition score and body weight were assessed daily. Semen collections
      (digital manipulation) were performed twice weekly for 14 weeks and blood samples
      (for plasma concentrations of cortisol and testosterone) were collected once a
      week. Dexamethasone treatment significantly reduced ejaculate volume and
      increased thiobarbituric acid-reactive substances (TBARS) in the seminal plasma.
      In contrast, supplementation with Vitamin E increased sperm motility, vigor and
      concentration and decreased the percentage of major sperm defects. In conclusion,
      dexamethasone treatment (to mimic stress) had a deleterious effect on the
      spermiogram and on the seminal plasma lipid peroxidation in dogs; however, some
      of these effects were prevented by oral supplementation with Vitamin E.

PMID- 16581117
TI  - Improved vitrification method allowing direct transfer of goat embryos.
AB  - The aim of this study was to design a vitrification method suited to field embryo
      transfer experiments in goat. In a first experiment, a standard vitrification
      protocol, previously designed for sheep embryos was compared to slow freezing of
      goat embryos. No significant difference was observed on kidding rate (48% versus
      69%, respectively), nor on embryo survival rate (35% versus 45%). Second
      experiment: all embryos were vitrified. After warming, embryos were either
      transferred directly (direct transfer), or after in vitro dilution of the
      cryoprotectants (conventional transfer). The kidding rate was not affected by the
      transfer method (38% versus 23%, respectively). However, embryo survival rate
      tended to be higher after direct transfer (26% versus 14%). Third experiment: OPS
      vitrification was compared to standard vitrification. The kidding rate was not
      affected (22% versus 39%, respectively), but the embryo survival rate was lower
      after OPS (14% versus 28%). Fourth experiment: 0.4M sucrose was added with
      cryoprotectants in vitrification. The kidding rate after direct transfer was
      significantly enhanced after addition of sucrose (56% versus 27%, respectively),
      whereas embryo survival rate was not significantly affected (32% versus 18%).
      Fifth experiment: vitrification with sucrose supplementation was compared to slow
      freezing. No significant difference was observed after direct transfer on kidding
      rate (52% versus 31%, respectively), but embryo survival rate tended to be higher
      after vitrification (34% versus 21%). In conclusion, our results indicate that
      addition of 0.4M sucrose in association with direct transfer improves
      significantly the viability of goat vitrified embryos.

PMID- 16581119
TI  - The relationship between monogamous/polygamous family structure and the mental
      health of bedouin Arab adolescents.
AB  - Previous studies of polygamy and child mental health have primarily focused on
      younger children. The present studies are among the first to focus on
      adolescents. The first study involved 210 randomly selected Bedouin Arab
      adolescents (mean age 15.9), who were administered instruments assessing their
      family environment and mental health. The second study involved 182 Bedouin Arab
      adolescents in which the student participants completed a single instrument about
      themselves and in which the teachers of the students completed the Teachers'
      Report Form of the Child Behaviour Checklist by Achenbach. The Bedouin Arab
      adolescents fell into two groups: (a) adolescents in monogamous family structures
      and (b) adolescents in polygamous family structures. The findings of the first
      study suggest that the two groups did not differ significantly in the majority of
      the assessed variables, even though there were significant differences obtained
      between groups for 4 of the 13 assessed variables. The two groups did not differ
      significantly in the second study. Results were discussed in terms of their
      cultural and developmental significance.

PMID- 16581118
TI  - Morphological and functional characteristics of chilled semen obtained from
      domestic feline epididymides (Felis catus).
AB  - The objective of this study was to determine morphological and functional
      characteristics of semen retrieved from the feline epididymis before and after
      cooling. Sixteen adult male cats were orchiectomized. The distal portion of the
      epididymis and proximal part of the deferent ducts were dissected and squeezed to
      obtain their content. After centrifugation, the supernatant was removed, sperm
      were resuspended in a 0.9 mL Tris-fructose-citric acid extender containing 20%
      egg yolk, aliquoted into three 0.3 mL samples, placed in a refrigerator (4.8
      degrees C) and cooled (0.5 degrees C/min). Semen evaluations were performed on
      four occassions: immediately after epididymal sperm retrieval (T0), and at 24 h
      (T1), 48 h (T2) and 72 h (T3) after cooling. On each occasion, progressive
      motility, vigor and sperm morphology were determined. Mean motility and vigor
      decreased (P < 0.05) between each successive examination. Although the majority
      of sperm cell damage occurred within the first 24 h, there was a decrease (P <
      0.05) in mean percentage of morphologically normal sperm between T0 and each
      evaluated time (T1, T2, T3) after cooling, due to an increase in coiled and bent
      sperm tails. Further studies are needed to evaluate the effects of cooling on the
      fertilizing capacity of cat epididymal spermatozoa in assisted reproduction
      programs.

PMID- 16581120
TI  - Biomimetic nanofibrous scaffolds: preparation and characterization of chitin/silk
      fibroin blend nanofibers.
AB  - Electrospinning of chitin/silk fibroin (SF) blend solutions in 1,1,1,3,3,3
      hexafluoro-2-propanol (HFIP) was investigated to fabricate a biomimetic
      nanostructured scaffolds for tissue engineering. The morphology of the
      electrospun chitin/SF blend nanofibers was investigated with a field emission
      scanning electron microscope (FE-SEM). The average diameters of chitin/SF blend
      fibers decreased from 920 to 340nm, with the increase of chitin content in blend
      compositions. The miscibility of chitin/SF blend fibers was examined by solution
      viscosity measurement. The chitin and SF were immiscible in the as-spun
      nanofibrous structure. The dimensional stability of chitin/SF blend nanofibers,
      with or without water vapor after-treatment, was conducted by immersing in water.
      As-spun SF-rich blend nanofibrous matrices were lost their fibrous structure
      after the water immersion for 24h, and then changed into membrane-like structure.
      On the contrary, nanofibrous structures of water vapor-treated SF-rich blends
      were almost maintained. To assay the cytocompatibility and cell behavior on the
      chitin/SF blend nanofibrous scaffolds, cell attachment and spreading of normal
      human epidermal keratinocyte and fibroblasts seeded on the scaffolds were
      studied. Our results indicate that chitin/SF blend nanofibrous matrix,
      particularly the one that contained 75% chitin and 25% SF, could be a potential
      candidate for tissue engineering scaffolds because it has both biomimetic three
      dimensional structure and an excellent cell attachment and spreading for NHEK and
      NHEF.

PMID- 16581121
TI  - Epigenetics and imprinting of the trophoblast -- a workshop report.
AB  - Genomic imprinting is a remarkable process that causes genes to be expressed or
      repressed depending on their parental-origin. Imprinted genes play important
      roles in prenatal growth and organ development. Postnatally, imprinted genes can
      contribute to the regulation of metabolic pathways and behaviour associated with
      the control of resources. One of the most important sites of imprinted gene
      action is the placenta. During this workshop at the 11th meeting of the
      International Federation of Placenta Associations/European Placenta Group held in
      Glasgow, a series of short talks were presented providing an overview of the
      evolution, function and mechanisms of imprinting in mammals with particular
      reference to the placenta. In addition, epigenetic control of trophoblast
      development and function were considered. This report summarises the
      contributions to the workshop.

PMID- 16581122
TI  - Relationship between ARLTS1 polymorphisms and risk of chronic lymphocytic
      leukemia.
AB  - ARLTS1, a member of the Ras superfamily and putative tumor-suppressor gene
      resides at chromosome 13q14, a region commonly deleted in hematopoietic and solid
      tumors. Previously, the truncating single nucleotide polymorphism (SNP) of ARLTS,
      G446A (W149X) has been reported to act as a multi-site tumor susceptibility
      allele. To explore the relationship between polymorphic variation in ARTLS1 and
      risk of chronic lymphocytic leukemia (CLL) we analyzed germline DNA from 413
      cases and 471 healthy controls for W149X and five additional coding SNPs, S99S,
      P131L, L132L, C148R, and E164K. A high proportion of the cases were familial,
      thereby empowering detection of an association. None of the SNPs were
      individually significantly associated with risk of CLL and there was no evidence
      for epistatic interaction between loci. Our study does not support the postulate
      that variants of ARLTS1 influence the risk of CLL.

PMID- 16581123
TI  - Production of human B cells from CD34+CD38- T- B- progenitors in organ culture by
      sequential cytokine stimulation.
AB  - We investigated sequential cytokine addition on human hematopoietic stem cell
      (HSC) differentiation in murine fetal liver (FL), fetal spleen (FS) and bone
      marrow (BM) organ cultures (OC). Tissues were colonized with unpurified or FACS
      sorted CD34+CD38-CD10-CD19-CD3-CD8-CD4-(T- B-) cells from human cord blood
      (HUCB). CD19+ cell production and kinetics differed in each tissue. Fetal liver
      organ cultures (FLOC) inoculated with CD34+CD38-T-B- cells produced fewer CD19+
      cells than fetal liver organ culture (FLOC) cultured with unpurified HUCB. CD19+
      cell production was restored in the CD34+CD38-T-B- organ cultures by treating
      with SCF, LIF and IL-6 followed by IL-7 and removing all cytokines for the last 3
      days of culture (a six-fold increase). FLOC also produced CD34+CD38-T-B- cells
      and monocyte-lineage CD33+CD14- cells, both of which increased after cytokine
      treatment. Re-colonization of secondary FLOC with CD34+CD38-T-B- cells generated
      in primary FLOC produced additional B-cells, monocytes and CD34+CD38- cells
      suggesting that the primary cells retained HSC activity. Expansion and
      differentiation of HSCs depended on the microenvironment of the recipient tissue
      as well as addition of cytokines in the appropriate order.

PMID- 16581124
TI  - Photochemistry of a major commercial polybrominated diphenyl ether flame
      retardant congener: 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE153).
AB  - The photochemistry of a major commercial polybrominated diphenyl ether (PBDE)
      flame retardant congener, 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE153), was
      investigated in acetonitrile, distilled water, and seawater. After a short
      irradiation period in acetonitrile at 302 nm, the major photoproducts of BDE153
      included 2,2',4,4',5-(BDE99), 2,2',4,5,5'-(BDE101), and 2,4,4',5,5'-(BDE118)
      substituted penta-BDEs as primary photohydrodebromination products, 2,2',4,4'
      (BDE47), 3,3',4,4'-(BDE77), 2,3',4,4'-(BDE66), and 2,2',4,5'-(BDE49) substituted
      tetra-BDEs as secondary photohydrodebromination products, a suite of non-2,3,7,8
      substituted mono- through penta-brominated dibenzofurans, and three
      tetrabrominated 2-hydroxybiphenyl congeners. By comparison, irradiation in
      distilled water and seawater gave increased relative photohydrodebromination
      contributions and no evidence for the formation of brominated dibenzofurans or 2
      hydroxybiphenyls. In all solvent systems, subsequent degradation of primary and
      secondary photoproducts under continuing irradiation led to a steadily decreasing
      reaction mass balance. The results suggest a short photochemical half-life for
      BDE153 in aquatic systems, with rapid photohydrodebromination to some of the most
      prevalent penta- and tetra-brominated diphenyl ether congeners typically observed
      in environmental matrices.

PMID- 16581125
TI  - Freudian snaps.
AB  - Sigmund Freud claimed to hate being photographed, yet he carefully fashioned his
      public image. Always immaculately dressed, he sported an old-fashioned beard that
      helped to establish his status as the founding father of psychoanalysis. An avid
      collector, Freud chose objects for their symbolic as well as their aesthetic
      interest.

PMID- 16581126
TI  - NASA and the search for life in the universe.
AB  - Almost from its beginnings in 1958, the National Aeronautics and Space
      Administration (NASA) set up a life-science program. Because one of the
      priorities of the organization is to search for life beyond Earth, NASA began
      designing spacecraft to unravel the mysteries of Mars. The effort to search for
      life on Mars culminated in the landing of two Viking spacecraft on the surface of
      the planet in 1976. Although the biology experiments conducted as part of these
      missions provided some evidence for the possibility of life, the scientific
      consensus was that they drew a blank. In 1996, however, the 'Mars rock' rekindled
      interest in life in our solar system. The discovery of an ocean on the Jovian
      moon Europa, of organic molecules on the Saturnian moon Titan and persuasive
      evidence that water once flowed on Mars suggests that the solar system is still
      of considerable exobiological interest. In addition, since 1995 approximately 175
      planets have been found beyond our solar system. Although these discoveries are
      gas giants, NASA spacecraft might soon detect Earth-sized planets. The search for
      life in the universe continues.

PMID- 16581127
TI  - Engineering fame: Isambard Kingdom Brunel.
AB  - Isambard Kingdom Brunel learnt the arts of self-promotion from his father, but
      triumphant images of him conceal failures and disappointments. This article (part
      of the Science in the Industrial Revolution series) focuses on his first and last
      great engineering projects--the Thames Tunnel and the Great Eastern steam-ship.

PMID- 16581128
TI  - Strongly enhanced IL-10 production using stable galectin-1 homodimers.
AB  - Galectin-1 is the homodimeric form of a protein, which is present in a dynamic
      equilibrium with the beta-galactoside monomeric form and has potent anti
      inflammatory and immunomodulating effects. These favorable effects are probably
      related to the induction of apoptosis in activated T cells and the induction of
      IL-10, which have been demonstrated to be characteristic for the dimeric form of
      the protein. Based on these findings it can be speculated that the in vivo
      effects of galectin-1 can be improved by the generation of stable galectin-1
      homodimers (dGal). To test this hypothesis we produced leucine-zipper based
      stable galectin-1 homodimers and tested its apoptosis inducing effects on MOLT-4
      cells and its immunomodulatory effects in vitro on PBMC of five independent
      donors. Phosphatidylserine exposure and a drop in mitochondrial membrane
      potential was strongly enhanced on MOLT-4 cells upon treatment with dGal as
      compared to wtGal. The minimal effective concentration was 20-fold reduced as
      compared to the minimal effective wtGal concentration. dGal showed enhanced
      induction of IL-10 on total PBMC as compared to treatment with wild-type protein
      (wtGal). The minimal effective dGal concentration was 100-fold lower than that of
      wtGal. Of the purified cell populations monocytes are the strongest IL-10
      producers, whereas T cells induce IL-10 at a lower level and no induction is
      observed in B cells. Besides induction of IL-10, dGal caused an increase in IL
      1beta production in all donors and a reduction of IL-2 production in 3 out of 5
      donors, whereas no consistent changes were observed for other inflammatory
      cytokines. In summary, we demonstrated that dGal shows enhanced effects at
      strongly reduced concentrations. Application of dGal may therefore serve as an
      improved treatment of chronic inflammatory diseases.

PMID- 16581129
TI  - Gangliosides, Ab1 and Ab2 antibodies I. Towards a molecular dissection of an
      idiotype-anti-idiotype system.
AB  - This report is focused on the molecular basis for the interaction of a monoclonal
      antibody (mAb) and its anti-idiotypic mAb. P3 mAb (Ab1) recognizes N-glycolyl
      gangliosides, and 1E10 mAb is one of its anti-idiotypic mAbs (Ab2). Chimeric
      versions of both antibodies retained their specificity. Charged residues in their
      H-CDRs, particularly H-CDR3, were considered to play a major role in their
      binding and immunogenic properties. P3 mAb has the unusual property of generating
      a strong antibody response in syngeneic mice, even when it is administered in
      saline. We selected phagotopes from a 12mer peptide library displayed on
      filamentous phage to characterize amino acid motifs recognized by these
      antibodies. The peptides were enriched in charged amino acids similar to those
      present in P3 and 1E10 mAb H-CDR3. We also report the construction of four
      mutants of the P3 antibody, where arginine residues in the heavy chain CDRs were
      substituted by serine residues, and the characterization of their interaction
      with 1E10 mAb and GM3(NeuGc) ganglioside, as well as their immunogenic properties
      in Balb/c mice. H-CDR1 R31 residue appears to have a central role in P3 mAb
      reactivity and antigenicity. H-CDR3 R100a residue seems to be more involved in
      the immunogenicity of the P3 idiotype.

PMID- 16581131
TI  - Extensive restrictions in the VH sequence usage of the human antibody response
      against the Rhesus D antigen.
AB  - Anti-Rhesus D immunoglobulin purified from human sera is used as a prophylactic
      reagent in Rhesus D negative women at risk of alloimmunization during pregnancy.
      We are currently developing a Rhesus D antigen-specific recombinant polyclonal
      antibody drug lead for replacing the existing blood derived-products. By
      analyzing the RhD-specific antibody VH repertoires from eight alloimmunized women
      we found, in agreement with previous studies, a strong preference for the VH 3-33
      "superspecies" gene segments which encompasses the IGHV3-30-3*01, IGHV3-30*18,
      and IGHV3-33*01 VH alleles. Even more extensive genetic restriction was observed
      among five donors, which produced antibodies of identical V-D-J usage and CDR3
      loop length and joining regions of similar amino acid composition. In addition,
      we find a high degree of sequence relatedness to previously isolated anti-Rhesus
      D antibodies. Such close homology in VH domains indicates that significant
      structural restrictions are operating in the selection of antibodies recognizing
      RhD as seen for T cell receptors. Moreover, some VH domains were isolated in
      their germline configuration indicating that anti-RhD antibodies of relatively
      high affinity are present in the naive antibody repertoire of Rhesus negative
      individuals which offers an explanation for the strong and clinically significant
      immunogenicity of the Rhesus D.

PMID- 16581130
TI  - Recognition profile of Morus nigra agglutinin (Morniga G) expressed by monomeric
      ligands, simple clusters and mammalian polyvalent glycotopes.
AB  - The carbohydrate binding properties of a novel member of the subfamily of
      galactose-specific jacalin-related lectin isolated from the bark of black
      mulberry (Morus nigra) (Morniga G) was studied in detail by enzyme-linked
      lectinosorbent and inhibition assays using panels of monomeric saccharides,
      mammalian polyvalent glycotopes and polysaccharides. Among the natural glycans
      tested for lectin binding, Morniga G reacted best with glycoproteins (gps)
      presenting a high density of tumor-associated carbohydrate antigens Tn
      (GalNAcalpha1-Ser/Thr) and Talpha (Galbeta1-3GalNAcalpha1-). Their reactivities,
      on a nanogram basis, were up to 72.5, 3.9x10(3), 6.0x10(3), 8.8x10(3) and
      2.9x10(4) times higher than that of Tn-containing glycopeptides (M.W.<3000 Da),
      monomeric T, Tn, GalNAc and Gal, respectively. It also reacted well with many
      multi-antennary N-glycans with II (Galbeta1-4GlcNAc) termini, ABH histo-blood
      group antigens and their precursors containing high densities of I/II and T/Tn
      glycotopes, and sialylated T/Tn. Among the mono-, di- and oligosaccharides
      tested, Thomsen-Friedenreich (T) disaccharide with aromatic aglycon [Galbeta1
      3GalNAcalpha1-benzyl (Talpha1-benzyl)] and Tn glycopeptides were the best
      inhibitors. Molecular modeling and docking studies indicated the occurrence of a
      primary GalNAcalpha1- and Galbeta1-3GalNAc glycotope-binding site in Morniga G.
      Using a recently proposed system [Wu, A.M., 2003. Carbohydrate structural units
      in glycoproteins and polysaccharides as important ligands for Gal and GalNAc
      reactive lectins. J. Biomed. Sci. 10, 676-688], the binding properties of the
      combining sites of Morniga G can be defined as follows: (i) the monosaccharide
      specificity is GalNAc/Gal>>Man/Glc, GlcNAc and lFuc; (ii) the mammalian glycotope
      specificity is Talpha1-benzyl>T>Tn>GalNAcbeta1-3Gal (P), while B/E (Galalpha1
      3/4Gal), I/II (Galbeta1-3/4GlcNAc), S (GalNAcbeta1-4Gal), F/A (GalNAcalpha1
      3GalNAc/Gal) and L (Galbeta1-4Glc) are inactive; (iii) the most active ligand is
      T/Tn; (iv) simple clustered Tn or triantennary N-glycans with II termini (Tri-II)
      have limited impact; (v) high-density polyvalent glycotopes play a prominent role
      for enhancing Morniga G reactivity. These results provide evidence for the
      binding of this lectin to dense cell surface T/Tn glycoconjugates and facilitate
      future usage of this lectin in biotechnological and medical applications.

PMID- 16581132
TI  - Post-transcriptional regulation of cytokine genes in fish: A role for conserved
      AU-rich elements located in the 3'-untranslated region of their mRNAs.
AB  - The overproduction of cytokines, such us interleukin-1beta (IL-1beta) and tumor
      necrosis factor alpha (TNFalpha), contributes to the pathological complications
      observed in many inflammatory diseases caused by bacterial endotoxins. The
      synthesis of these cytokines is tightly regulated at both transcriptional and
      post-transcriptional levels. Post-transcriptional regulation of gene expression
      depends on specific cis-acting sequences and trans-acting factors. Thus, the
      presence of adenylate- and uridylate-rich (AU-rich) elements (AREs) has been
      described in the 3'-untranslated regions (UTRs) of many unstable mammalian mRNAs.
      Although, it represents the most widespread, phylogenetically conserved and
      efficient determinant of mRNA stability among those so far characterized in
      mammalian cells, no studies are available on the functional relevance of this
      sequence in non-mammalian vertebrates. In this contribution, we study the
      enzymatic activity of various luciferase reporter constructs, containing or
      lacking the 3'UTR of IL-1beta and TNFalpha from different fish species, and
      report the finding that bony fish AREs are able to decrease luciferase activity
      but are less potent than their mammalian counterparts. Surprisingly, the 3'UTR of
      the IL-1beta from the cartilaginous fish small spotted catshark had the greatest
      ability to decrease luciferase activity. Lastly, the functional significance of
      the above was confirmed by measuring the half-life of IL-1beta and TNFalpha mRNAs
      in gilthead seabream leukocytes by blocking transcription with actinomycin D.
      Both cytokine mRNAs were unstable with an estimated half-life of about 45 min in
      control and activated cells.

PMID- 16581133
TI  - Potential inhibition of somatic hypermutation by nucleoside analogues.
AB  - Somatic hypermutation, which occurs in antigen-activated germinal centre B
      lymphocytes, diversifies the genes that encode immunoglobulin variable regions
      and leads to the 'affinity maturation' of the humoral immune response.
      Hypermutation affects dC/dG and dA/dT pairs with approximately equal frequency in
      vivo. DNA polymerase-theta contributes to hypermutagenesis at dC/dG pairs and DNA
      polymerase-eta is substantially involved in the generation of hypermutations at
      dA/dT pairs. The biochemical properties of polymerases-theta and -eta indicate
      that their DNA synthetic activities are potentially susceptible to inhibition by
      nucleoside analogues, so it is feasible that nucleoside analogues reduce the
      accumulation of dC/dG- and dA/dT-targeted hypermutations in vivo. Nucleoside
      analogues could hence impair the humoral adaptive immune response of HIV-infected
      patients who are prescribed these chemotherapeutic agents.

PMID- 16581134
TI  - Not another case of endocarditis: recurrent prosthetic valve dehiscense in a
      Chinese man.

PMID- 16581135
TI  - Selective, reversible occlusion of the middle cerebral artery in rats by an
      intraluminal approach. Optimized filament design and methodology.
AB  - These studies optimized design and application of an intraluminal filament method
      to achieve selective middle cerebral artery (MCA) occlusion in rats. Silicone
      plugs of 300 microm diameter and 700-800 microm length were molded onto 6-0
      suture. These were introduced into Wistar rats previously fitted with telemetric
      probes, using established placement procedures, with and without heparinization.
      Temperature and activity were monitored for 3 days, after which lesion volumes
      were assessed by triphenyltetrazolium chloride staining. Optimized filaments
      entered the MCA in 85% of Wistar rats, failures being attributable to anatomical
      variation at its origin from the internal carotid artery. Infarcts restricted to
      the MCA territory were apparent after 90 min occlusion, and maximal after 3 h
      occlusion. Intraischemic hyperthermia was noted in a third of occlusions
      performed without heparin, but never with anticoagulant treatment. Permanent
      occlusions were also evaluated in Fisher, Lewis, Long-Evans, Spontaneously
      Hypertensive and Sprague-Dawley rats, and Wistar rats from a second supplier, and
      compared with data for surgical MCA occlusions. Success rates varied among
      strains, but infarct volumes correlated with those obtained after surgical
      occlusions in respective populations. These studies demonstrate the feasibility
      and limitations of reversible and selective intraluminal filament occlusion of
      the MCA in rats.

PMID- 16581136
TI  - A novel suction electrode recording technique for monitoring circadian rhythms in
      single and multiunit discharge from brain slices.
AB  - The study of spontaneous neuronal discharge for several days in vitro poses
      substantial technical difficulties not readily addressed by existing
      methodologies. Here we describe a novel method for recording bioelectrical
      signals from brain slices, using media-filled, glass micropipettes stabilized at
      the recording interface by negative pressure. Such electrodes are durable,
      economical and easily constructed using standard laboratory equipment. Through
      these suction electrodes, we monitored approximately 24 h oscillations in
      spontaneous single and multiunit discharge from acutely prepared adult mouse
      suprachiasmatic nuclei (SCN) slices for up to 4 days in vitro, with very high
      success rates. Neuronal oscillations exhibited all the characteristics previously
      determined in SCN recordings using other techniques. Importantly, our electrode
      assembly enables SCN activity in acutely prepared brain slices to be monitored
      for substantially longer than with other methodologies. In summary, our data
      suggest that suction electrodes are likely to provide a favorable alternative to
      existing methods for recording long-term neuronal activity from brain slices.

PMID- 16581137
TI  - Practical nerve morphometry.
AB  - Histopathological examination of peripheral nerves is often complemented by
      morphometric analysis in both clinical and research settings. However, existing
      manual or semi-automated methods are highly tedious, labour intensive and time
      consuming, whereas fully automated morphometry is prone to error from the
      conversion of maldetected particles to spurious data. Both fully and interactive
      automated morphometry have significant hardware requirements and may be difficult
      to implement. A new method for nerve morphometry is described aiming to combine
      the speed of automated morphometry with the accuracy of manual or semi-automated
      methods, and requiring only a digital image of the nerve section and two widely
      available software packages. Comparison with a standard digitizer pen method of
      nerve morphometry without sampling yielded statistically similar axon counts,
      mean area assessments and axonal area frequency distribution histograms, with
      assessment times of the new method between 35% and 45% of those of the standard
      method. This has widespread potential experimental and clinical applications and
      offers a means of relieving much of the tedium currently associated with nerve
      morphometry.

PMID- 16581139
TI  - Comparison between denaturing gradient gel electrophoresis and phylogenetic
      analysis for characterization of A/H3N2 influenza samples detected during the
      1999-2004 epidemics in Brazil.
AB  - In a preliminary study, a denaturing gradient gel electrophoresis method (DGGE)
      was described for influenza virus variants screening [Motta, F.C., Rosado, A.S.,
      Couceiro, J.N.S.S., 2002. Standardization of denaturing gradient gel
      electrophoresis for mutant screening of influenza A (H3N2) virus samples. J.
      Virol. Meth. 105, 105-115]. Such a protocol has confirmed its usefulness,
      discriminating closely related samples by the evaluation of the HA1 portion of
      haemagglutinin coding RNA segment. In this study, the HA1 sequence/phylogenetic
      analysis was compared with DGGE results to evaluate the degree of agreement
      between these methods. Forty-one influenza clinical samples characterized as the
      A/H3 subtype by a multiplex-PCR throughout 1999-2004 epidemics were chosen at
      random. The 569 bp DGGE amplicons were generated by nested-PCR using the first
      round multiplex-PCR product as template. The amplicons were analyzed on a 6%
      polyacrylamide gel with a urea-formamide gradient (25-35%) at 60 degrees C/150
      V/5 h, being differentiated by their melting profiles. Even with the multiple
      melting domains characteristic of the region used in this study, the 41 samples
      could be grouped in 7 distinct clusters by DGGE. Five of the clusters reproduced
      exactly the phylogenetic tree topology, including the most external branches.
      Although the other two clusters demonstrated a poorer match, the internal genetic
      correlations were conserved, and just four samples were grouped incorrectly in
      comparison with the phylogenetic results. The results demonstrated the usefulness
      of this method for screening of variant samples throughout or in subsequent
      epidemics, thus improving the detection of influenza variants.

PMID- 16581140
TI  - A simplified cloning strategy for the generation of an endothelial cell selective
      recombinant adenovirus vector.
AB  - Specifically targeting adenoviral vectors to particular cell/tissue types can be
      achieved by genetically modifying the adenovirus fiber protein. Two common
      strategies are: (1) directly modifying the fiber gene in the adenovirus genome
      and (2) in trans supply of the modified fiber. The former however, suffers from
      difficulties in directly manipulating large adenoviral genomic DNA. Although the
      latter allows easy manipulation of the small fiber gene, our studies show that
      the in trans supplement of the modified fiber causes incomplete fiber
      assimilation in the virus. Thus an alternate cloning strategy was devised to
      facilitate the insertion of cell-targeting sequences into the HI loop of a CAR
      binding-ablated fiber gene in the Ad5 genomic backbone. Our approach retains the
      advantage of easily modifying the fiber with the additional benefit of genetic re
      insertion into the Ad genomic backbone to ensure complete modified fiber
      incorporation. Using this strategy, an endothelial cell binding peptide sequence
      (Asn-Gly-Arg) was introduced into the Ad fiber and showed that the generated Ad
      vector displayed selective transduction of endothelial cells both in vitro and in
      vivo compared to the conventional vector. Furthermore, this Ad vector cloning
      strategy can be adapted to introduce other peptide sequences to target other cell
      types.

PMID- 16581141
TI  - Evaluation of methyl inosine monophosphate (MIMP) and peramivir activities in a
      murine model of lethal influenza A virus infection.
AB  - An inbred murine model (BALB/c) was utilized to assess the protective effect of
      the immunomodulator methyl inosine 5'-monophosphate (MIMP) against infection with
      influenza A/PR/8/34 (H1N1) virus. Contrary to the data reported for outbred mice
      (NMRI) infected with the aerosolized virus (Masihi, Hadden, 2003. J. Int.
      Immunopharmacol. 3, 1205-1215), there were no improvements in the outcomes of
      infection in the inbred animals treated with MIMP intranasally 1 day before the
      challenge and/or orally after the challenge for 5 days (up to 10 mg/kg/day).
      Nevertheless, complete protection against lethality was afforded by the treatment
      with the neuraminidase inhibitor peramivir given once daily for 5 days after the
      challenge (10 mg/kg/day). We speculate that the rapid progression of the disease
      in inbred mice caused by the intranasal challenge may render the MIMP-treatment
      ineffective. Our results emphasize the need for careful consideration of murine
      strains and routes of virus challenge in the design of experiments utilizing
      lethal influenza virus infection.

PMID- 16581142
TI  - Edible bird's nest extract inhibits influenza virus infection.
AB  - Edible bird's nest (EBN) is the nest of the swift that is made from its saliva.
      Although EBN has been widely used for enhancing immunocompetence, its antiviral
      efficacy has not been studied in detail. We found that EBN extract could strongly
      inhibit infection with influenza viruses in a host range-independent manner when
      it was hydrolyzed with Pancreatin F. Western blotting assay showed that the EBN
      extract bound to influenza virus. Furthermore, EBN extract could neutralize the
      infection of MDCK cells with influenza viruses and inhibit hemagglutination of
      influenza viruses to erythrocytes, but it could not inhibit the activity of
      influenza virus sialidase. Fluorometric HPLC indicated that the major molecular
      species of sialic acid in EBN is N-acetylneuraminic acid. The results suggest
      that EBN is a safe and valid natural source for the prevention of influenza
      viruses.

PMID- 16581143
TI  - Expression of cytoskeletal proteins, cross-reacting with anti-CYP1A, in Mytilus
      sp. exposed to organic contaminants.
AB  - The possible use of cytoskeletal components as biomarkers of organic pollution in
      mussels has been investigated. Responses of non-muscular actin and tropomyosin
      (TM), two bivalve proteins that were recently demonstrated to cross-react with
      anti-fish-CYP1A, were analysed in digestive tissue of blue mussels (Mytilus sp.)
      exposed to a wide range of organic contaminants. The results were evaluated with
      ELISA and Western blot assays, utilising commercial monoclonal antibodies, and
      compared with expression of Hsp70, a marker of chemical stress. Furthermore,
      mussels were sampled from the Baltic Sea at sites with different degrees of
      pollution to assess the expression of these proteins, and to monitor seasonal
      changes in relation to energy reserves and water temperature. The results
      demonstrated that expression of microsomal actin was significantly higher
      (p<0.02) in mussels exposed to a brominated flame retardant (BDE-47), and lower,
      however not significantly, in specimens exposed to crude oil, alone and spiked
      with alkylphenols and PAHs. Hsp70 was strongly induced in all exposure groups,
      which also included bisphenol A and diallylphthalate. Furthermore, microsomal
      actin exhibited seasonal variations, and expression was negatively correlated
      with water temperature. No correlation was seen between actin and the
      microfilament-binding protein TM, indicating that regulation of these two
      cytoskeletal components are not coupled. Furthermore, parallel and significant
      (p<0.05) up-regulations of TM and Hsp70 were seen in individuals sampled from a
      strongly polluted field site, whereas the seasonal analysis showed that TM
      expression was positively correlated with energy reserves (total glycogen
      content) in mussels, suggesting the use of TM as a marker of growth. In
      conclusion, this study has demonstrated the cytoskeleton to be a target of
      contaminants in mussels, calling for further attention. Exposure-induced increase
      of microsomal actin can be interpreted either as stimulated actin synthesis, or
      re-arrangements of the dynamic microfilaments.

PMID- 16581144
TI  - Redefining heart failure.

PMID- 16581145
TI  - Utilization of glycoprotein IIb/IIIa inhibitors in non-ST-elevation acute
      myocardial infarction in a tertiary referral medical center in a developing
      country.
AB  - We analyze the patterns of utilization of glycoprotein (GP) IIb/IIIa inhibitors
      in patients with non-ST-elevation myocardial infarction (NSTEMI) in a tertiary
      medical center in a developing country and we compare it to data from the
      national registry of myocardial infarction 4 (NRMI 4) in the USA. GP IIb/IIIa
      inhibitors were used in 28% of patients. The significant multivariate predictors
      of GP IIb/IIIa inhibitors utilization were Age <70 years (p=0.05), TIMI score >
      or =4 (p=0.002), and the absence of congestive heart failure (p=0.01) or prior
      infarction (p=0.04). Our results show striking similarity to what has been
      reported by the NRMI 4 registry, in terms of the overall underutilization of GP
      IIb/IIIa inhibitors in NSTEMI patients, and particularly in elderly patients and
      women. These findings underscore the importance of initiating a worldwide
      campaign to educate physicians about the pivotal role of GP IIb/IIIa inhibitors
      in the management of patients with NSTEMI.

PMID- 16581147
TI  - Lights and shadows in the current management of acute myocardial infarction in
      the elderly.

PMID- 16581146
TI  - Prolonged intravenous eptifibatide infusion for prevention of coronary stent
      thrombosis.
AB  - Coronary bare-metal stent thrombosis usually occurs within a week of angioplasty,
      and may result in myocardial infarction and death. Thrombosis is effectively
      prevented by antiplatelet therapy with aspirin and clopidogrel. We describe a
      patient who was unable to ingest oral medication after angioplasty due to
      gastrointestinal surgery, and was therefore at risk for stent thrombosis.
      Intravenous eptifibatide was infused for 8 days in order to achieve parenteral
      platelet inhibition. We suggest a role for long-term intravenous administration
      of glycoprotein IIb/IIIa inhibitors for prevention of stent thrombosis in
      patients unable to take oral antiplatelet therapy.

PMID- 16581148
TI  - Adjusted incidence risks of BSE in risk subpopulations of cattle in Japan.
AB  - Immediately after the detection of the first case of BSE in 2001, the Japanese
      government introduced active surveillance targeting fallen-stock and all cattle
      slaughtered for human consumption. By the end of 2004, four million animals were
      tested with rapid tests under the passive and active surveillance. As a result 13
      additional cases were detected. I focused on the 1996 birth cohort, in which nine
      cases of BSE were detected during 2001-2004, and estimated the prevalence of BSE
      infection of that birth cohort using maximum-likelihood methods. Using the
      estimated prevalence of infection as an input variable, I calculated the adjusted
      incidence risk of BSE by different ages and risk subpopulations (clinical
      suspects, fallen-stock, sick-slaughter and healthy-slaughter animals). The
      adjusted incidence risk of BSE in sick-slaughter animals (animals showing
      clinical signs not compatible with BSE when slaughtered for human consumption)
      was 18.7 and 4.5-78.4 times higher than the incidence risk in fallen-stock and
      healthy-slaughter animals, respectively.

PMID- 16581149
TI  - Clinical application of a repositioning scheme, using gold markers and electronic
      portal imaging.
AB  - BACKGROUND AND PURPOSE: To implement an on-line correction scheme based on
      implanted markers to reduce treatment margins in external beam radiation therapy
      (EBRT) of carcinoma of the prostate. In turn reduction in treatment margins
      reduces irradiated volumes and offers the possibility of reduced normal tissue
      complications or escalated target dose. PATIENTS AND METHODS: Five or six gold
      markers were implanted in 10 patients treated for prostate carcinoma using EBRT.
      All patients were enlisted in an IRB-approved protocol. Before each fraction two
      portal images were obtained using a low dose (2MU). Positions of the markers were
      calculated from these images using an in-house developed program. Corrections
      were applied with a threshold of 2mm displacement. After correction the procedure
      was repeated. RESULTS: Overall systematic errors were reduced from 7.45, 1.29,
      and 5.12 mm to 0.65, 0.11, and 0.46 mm in, respectively, the antero-posterior,
      lateral, and cranio-caudal directions. Likewise, the overall SD were reduced from
      5.99, 5.34, and 4.44 mm to 2.82, 2.64, and 2.22 mm, respectively. All reductions
      were highly significant (P < 0.01) using a t-test for systematic and an F-test
      for random errors. On an individual level all but three patients showed
      significant improvements in all directions for the random errors. All patients
      improved in at least one direction. Systematic errors were significantly lower in
      all patients. Simulated correction schemes using this data suggest that margin
      reduction using off-line reduction does not benefit substantially from on-line
      corrections in the first few fractions. CONCLUSIONS: Use of marker-based
      correction improves the patient position. Factors influencing the accuracy were:
      (1) number of seeds usable for correction, (2) distribution of markers throughout
      the volume of interest, and (3) objective instructions for patient realignment.

PMID- 16581151
TI  - Effects of propranolol on venous compliance in conscious rats with pre-hepatic
      portal hypertension.
AB  - BACKGROUND/AIMS: The venous system is the primary capacitance region in the body.
      However, the influence of active changes in the venous system on the hemodynamic
      alterations of portal hypertension is poorly understood. To investigate venous
      compliance (VC) in conscious partial portal vein ligated rats (PPVL) and the
      effect of propranolol on VC. METHODS: Venous compliance was derived from the
      relationship between changes in mean circulatory filling pressure (MCFP) and
      changes in blood volume (BV). Measurements were performed before and after i.v.
      propranolol (7.5 mg/Kg) or placebo in rats with portal hypertension due to PPVL
      and sham operated controls. RESULTS: PPVL rats had an increased VC when compared
      to Sham (4.9+/-1.4 vs. 3.7+/-0.9 ml kg-1 mm Hg-1; P<0.02). VC did not change
      after placebo but was significantly reduced by Propranolol in PPVL (-32.9+/
      15.7%; P<0,007). Propranolol did not modify venous compliance in sham operated
      rats (+10.9+/-13.4%; P=ns). CONCLUSIONS: Venous compliance is increased in portal
      hypertensive rats, suggesting that the venous system contributes to the profound
      circulatory changes encountered in portal hypertension. The increased venous
      compliance is markedly attenuated by propranolol, suggesting that this
      abnormality is related to increased adrenergic activity.

PMID- 16581150
TI  - Purification, characterization, and synergistic action of phytate-resistant alpha
      amylase and alpha-glucosidase from Geobacillus thermodenitrificans HRO10.
AB  - The alpha-amylase (1, 4-alpha-d-glucanohydrolase; EC 3.2.1.1) and alpha
      glucosidase (alpha-d-glucoside glucohydrolase; EC 3.2.1.20) secreted by
      Geobacillus thermodenitrificans HRO10 were purified to homogeneity (13.6-fold;
      11.5% yield and 25.4-fold; 32.0% yield, respectively) through a series of steps.
      The molecular weight of alpha-amylase was 58kDa, as estimated by sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The alpha-amylase
      activity on potato starch was optimal at pH 5.5 and 80 degrees Celsius. In the
      presence of Ca(2+), the alpha-amylase had residual activity of more than 92%
      after 1h of incubation at 70 degrees Celsius. The alpha-amylase did not lose any
      activity in the presence of phytate (a selective alpha-amylase inhibitor) at
      concentrations as high as 10mM, rather it retained 90% maximal activity after 1h
      of incubation at 70 degrees Celsius. EGTA and EDTA were strong inhibitory
      substances of the enzyme. The alpha-amylase hydrolyzed soluble starch at 80
      degrees Celsius, with a K(m) of 3.05mgml(-1) and a V(max) of 7.35Uml(-1). The
      molecular weight of alpha-glucosidase was approximately 45kDa, as determined by
      SDS-PAGE. The enzyme activity was optimal at pH 6.5-7.5 and 55 degrees Celsius.
      Phytate did not inhibit G. thermodenitrificans HRO10 alpha-glucosidase activity,
      whereas pCMB was a potent inhibitor of the enzyme. The alpha-glucosidase
      exhibited Michaelis-Menten kinetics with maltose at 55 degrees Celsius (K(m):
      17mM; V(max): 23micromolmin(-1)mg(-1)). Thin-layer chromatography studies with G.
      thermodenitrificans HRO10 alpha-amylase and alpha-glucosidase showed an excellent
      synergistic action and did not reveal any transglycosylation catalyzed reaction
      by the alpha-glucosidase.

PMID- 16581152
TI  - Fast normalized cross correlation for motion tracking using basis functions.
AB  - Digital image-based elasto-tomography (DIET) is an emerging method for non
      invasive breast cancer screening. Effective clinical application of the DIET
      system requires highly accurate motion tracking of the surface of an actuated
      breast with minimal computation. Normalized cross correlation (NCC) is the most
      robust correlation measure for determining similarity between points in two or
      more images providing an accurate foundation for motion tracking. However, even
      using fast Fourier transform (FFT) methods, it is too computationally intense for
      rapidly managing several large images. A significantly faster method of
      calculating the NCC is presented that uses rectangular approximations in place of
      randomly placed landmark points or the natural marks on the breast. These
      approximations serve as an optimal set of basis functions that are automatically
      detected, dramatically reducing computational requirements. To prove the concept,
      the method is shown to be 37-150 times faster than the FFT-based NCC with the
      same accuracy for simulated data, a visco-elastic breast phantom experiment and
      human skin. Clinically, this approach enables thousands of randomly placed points
      to be rapidly and accurately tracked providing high resolution for the DIET
      system.

PMID- 16581153
TI  - Zotarolimus (ABT-578) eluting stents.
AB  - Drug-eluting stents have revolutionized the field of interventional cardiology
      and have provided a significant innovation for preventing coronary artery
      restenosis. Polymer coatings that deliver anti-proliferative drugs to the vessel
      wall are key components of these revolutionary medical devices. This article
      focuses on the development of stents which elute the potent anti-proliferative
      agent, zotarolimus, from a synthetic phosphorylcholine-based polymer known for
      its biocompatible profile. Zotarolimus is the first drug developed specifically
      for local delivery from stents for the prevention of restenosis and has been
      tested extensively to support this indication. Clinical experience with the PC
      polymer is also extensive, since more than 120,000 patients have been implanted
      to date with stents containing this non-thrombogenic coating. This review
      provides background on pre-clinical studies with zotarolimus, on the development
      of the biocompatible PC polymer and on the clinical trials conducted using two
      stent platforms which deliver this drug to patients with coronary artery disease.

PMID- 16581154
TI  - Flux-based assessment at a manufacturing site contaminated with
      trichloroethylene.
AB  - Groundwater and contaminant fluxes were measured, using the passive flux meter
      (PFM) technique, in wells along a longitudinal transect passing approximately
      through the centerline of a trichloroethylene (TCE) plume at a former
      manufacturing plant located in the Midwestern US. Two distinct zones of hydraulic
      conductivity were identified from the measured groundwater fluxes; a 6-m-thick
      upper zone ( approximately 7 m to 13 m below the ground surface or bgs) with a
      geometric mean Darcy flux (q(0)) of 2 cm/day, and a lower zone ( approximately 13
      m to 16.5m bgs) with a q(0) approximately 15 cm/day; this important hydrogeologic
      feature significantly impacts any remediation technology used at the site. The
      flux-averaged TCE concentrations estimated from the PFM results compared well
      with existing groundwater monitoring data. It was estimated that at least 800 kg
      of TCE was present in the source zone. The TCE mass discharge across the source
      control plane (85 m x 38 m) was used to estimate the "source strength" (
      approximately 365 g/day), while mass discharges across multiple down-gradient
      control planes were used to estimate the plume-averaged, TCE degradation rate
      constant (0.52 year(-1)). This is close to the rate estimated using the
      conventional centerline approach (0.78 year(-1)). The mass discharge approach
      provides a more robust and representative estimate than the centerline approach
      since the latter uses only data from wells along the plume centerline while the
      former uses all wells in the plume.

PMID- 16581156
TI  - Fusion of synaptic vesicles and plasma membrane in the presence of synaptosomal
      soluble proteins.
AB  - Fusion between synaptic vesicles and plasma membranes isolated from rat brain
      synaptosomes is regarded as a model of neurosecretion. The main aim of current
      study is to investigate whether the synaptosomal soluble proteins are essential
      members of Ca(2+)-triggered fusion examined in this system. Fusion experiments
      were performed using fluorescent dye octadecylrhodamine B, which was incorporated
      into synaptic vesicle membranes at self-quenching concentration. The fusion of
      synaptic vesicles, containing marker octadecylrhodamine B, with plasma membranes
      was detected by dequenching of the probe fluorescence. Membrane fusion was not
      found in Ca(2+)-supplemented buffer solution, but was initiated by the addition
      of the synaptosomal soluble proteins. When soluble proteins were treated with
      trypsin, they lost completely the fusion activity. These experiments confirmed
      that soluble proteins of synaptosomes are sensitive to Ca(2+) signal and
      essential for membrane fusion. The experiments, in which members of fusion
      process were treated with monoclonal antibodies raised against synaptotagmin and
      synaptobrevin, have shown that antibodies only partially inhibited fusion of
      synaptic vesicles and plasma membranes in vitro. These results indicate that
      other additional component(s), which may or may not be related to synaptobrevin
      or synaptotagmin, mediate this process. It can be assumed that fusion of synaptic
      vesicles with plasma membranes in vitro depends upon the complex interaction of a
      large number of protein factors.

PMID- 16581155
TI  - Guidelines for the control and prevention of meticillin-resistant Staphylococcus
      aureus (MRSA) in healthcare facilities.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) remains endemic in many UK
      hospitals. Specific guidelines for control and prevention are justified because
      MRSA causes serious illness and results in significant additional healthcare
      costs. Guidelines were drafted by a multi-disciplinary group and these have been
      finalised following extensive consultation. The recommendations have been graded
      according to the strength of evidence. Surveillance of MRSA should be undertaken
      in a systematic way and should be fed back routinely to healthcare staff. The
      inappropriate or unnecessary use of antibiotics should be avoided, and this will
      also reduce the likelihood of the emergence and spread of strains with reduced
      susceptibility to glycopeptides, i.e. vancomycin-intermediate S.
      aureus/glycopeptide-intermediate S. aureus (VISA/GISA) and vancomycin-resistant
      S. aureus (VRSA). Screening for MRSA carriage in selected patients and clinical
      areas should be performed according to locally agreed criteria based upon
      assessment of the risks and consequences of transmission and infection. Nasal and
      skin decolonization should be considered in certain categories of patients. The
      general principles of infection control should be adopted for patients with MRSA,
      including patient isolation and the appropriate cleaning and decontamination of
      clinical areas. Inadequate staffing, especially amongst nurses, contributes to
      the increased prevalence of MRSA. Laboratories should notify the relevant
      national authorities if VISA/GISA or VRSA isolates are identified.

PMID- 16581157
TI  - Rat brain proteome in morphine dependence.
AB  - The aim of this study was to reveal potential markers associated with drug
      dependence, using the proteomic approach. Gels containing samples derived from
      morphine-treated and control animals were compared and analyzed. Inspection of
      protein profiles, following TCA/acetone precipitation and the use of nano-scale
      liquid chromatography coupled to tandem mass spectrometry, allowed for
      identification of eleven potential dependence markers, mainly cytoplasmic and
      mitochondrial enzymes, e.g. proteins that belong to GTPase and GST superfamilies,
      ATPase, asparaginase or proteasome subunit p27 families.

PMID- 16581159
TI  - A short report on highlights of world-wide development of RIX4414: an European
      experience.

PMID- 16581158
TI  - Cytotoxic 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienes mounted on alicyclic
      scaffolds.
AB  - The 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienyl pharmacophore was incorporated
      into four series of compounds 1-4. Compounds 1a-g comprised a cluster of 3
      arylidene-1-(4-nitrophenylmethylene)-2-oxo-3,4-dihydro-1H-naphthalenes while the
      analogues 2a-g consisted of a group of 6-arylidene-2-(4
      nitrophenylmethylene)cyclohexanones. Three other compounds prepared in this study
      were 1-(4-nitrophenylmethylene)-3-(3,4,5-trimethoxyphenylmethylene)-2-oxo-2,3
      dihydro-1H-indene 3a as well as two 5-arylidene-2-(4
      nitrophenylmethylene)cyclopentanones 4a,b. The compounds were evaluated against
      human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 cells. In general,
      the compounds in series 1 displayed marked cytotoxicity having IC50 values in the
      1-5 microM range while the related cyclohexyl analogues in series 2 were slightly
      less potent (IC50 figures were mainly 5-10 microM). The relative locations of two
      aryl rings present in all four series were considered to contribute significantly
      to bioactivity and may have accounted for the virtual absence of cytotoxic
      properties in series 3 and 4. Most of the compounds were administered
      intraperitoneally to mice using doses up to and including 300 mg/kg. No
      mortalities were noted. The inhibiting effect of most of the compounds towards
      Helicobacter pylori is noteworthy. The modes of action of representative
      compounds include the induction of apoptosis while some compounds weakly
      inhibited tubulin polymerisation and human N-myristoyltransferase.

PMID- 16581160
TI  - Expression of enterotoxigenic Escherichia coli colonization factors in Vibrio
      cholerae.
AB  - As a first step towards a vaccine against diarrhoeal disease caused by
      enterotoxigenic Escherichia coli (ETEC), we have studied the expression of
      several ETEC antigens in the live attenuated Vibrio cholerae vaccine strain CVD
      103-HgR. Colonization factors (CF) CFA/I, CS3, and CS6 were expressed at the
      surface of V. cholerae CVD 103-HgR. Both CFA/I and CS3 required the co-expression
      of a positive regulator for expression, while CS6 was expressed without
      regulation. Up-regulation of CF expression in V. cholerae was very efficient, so
      that high amounts of CFA/I and CS3 similar to those in wild-type ETEC were
      synthesized from chromosomally integrated CF and positive regulator loci.
      Increasing either the operon and/or the positive regulator gene dosage resulted
      in only a small increase in CFA/I and CS3 expression. In contrast, the level of
      expression of the non-regulated CS6 fimbriae appeared to be more dependent on
      gene dosage. While CF expression in wild-type ETEC is known to be tightly
      thermoregulated and medium dependent, it seems to be less stringent in V.
      cholerae. Finally, co-expression of two or three CFs in the same strain was
      efficient even under the control of one single regulator gene.

PMID- 16581162
TI  - 'Combined vaccines are like a sudden onslaught to the body's immune system':
      parental concerns about vaccine 'overload' and 'immune-vulnerability'.
AB  - The recent controversy surrounding the safety of the measles, mumps, and rubella
      vaccine (MMR) has heightened parents' concerns about the safety of vaccines, and
      led some to believe that giving vaccines in a combined form may 'overload'
      children's immune systems. However, to date no studies have been published
      examining how British parents conceptualise the notion of 'immune-overload' or
      how they relate this concept to their own children. Eighteen focus groups were
      conducted with parents between November 2002 and March 2003. The literature on
      vaccine decision-making suggests that parents base their immunisation decisions
      on two key risks: those posed by the diseases, and those associated with the
      vaccines aimed at preventing those diseases. Our study suggested that for some
      parents a third factor plays an important role, namely their assessment of the
      ability of their child's immune system to 'cope' with the challenge of combined
      vaccines, or to fight the disease. We conclude that although there is no
      scientific evidence that supports parents' fears about combined vaccines causing
      'immune-overload', policy makers need to recognise these concerns if they are to
      successfully persuade parents that combined vaccines are safe.

PMID- 16581161
TI  - Immunogenicity and safety of a novel therapeutic hepatitis C virus (HCV) peptide
      vaccine: a randomized, placebo controlled trial for dose optimization in 128
      healthy subjects.
AB  - As interferon/ribavirin-based standard therapy is curative in only about half of
      HCV patients, there remains an important need for alternatives including
      vaccines. The novel peptide vaccine IC41 consists of five synthetic peptides
      harboring HCV T cell epitopes and poly-L-arginine as synthetic adjuvant. In this
      randomized, placebo-controlled trial, 128 HLA-A2 positive healthy volunteers
      received four s.c. vaccinations of seven different doses IC41, HCV peptides
      alone, poly-l-arginine alone or saline solution, every 4 weeks. IC41 was safe and
      well tolerated. Mild to moderate local reactions were transient. Immunogenicity
      was assessed using T cell epitope specific [3H]-thymidine proliferation, IFN
      gamma ELIspot and HLA-tetramer assays. IC41 induced responses in all dose groups.
      Higher responder rates were recorded in higher dose groups and increasing number
      of vaccinations were associated with higher responder rates and more robust
      responses. Poly-L-arginine was required for the aimed-for Th1/Tc1-type immunity
      (IFN-gamma secreting T cells).

PMID- 16581163
TI  - Long-term immunity in young adults after a single dose of inactivated Hepatitis A
      vaccines.
AB  - We evaluated in a prospective study the immune response of naive subjects to a
      single dose of inactivated Hepatitis A vaccine. Ninety-seven percent of the
      vaccinees sero-converted 1 month after vaccination and 93% were still positive 2
      years later. All of the vaccinees had a strong booster response 2 years after the
      single dose. Avaxim was more immunogenic than Vaqta for the primary dose (p =
      0.01 for sero-positivity, p<0.001 for antibody level) but no differences were
      found after boosting with Avaxim. Performance of intense physical activity during
      the first month after a single vaccine dose was associated with lower antibody
      levels (p = 0.004). This study indicates that a single dose of inactivated HAV
      vaccine elicits protective immune memory for at least 2 years.

PMID- 16581164
TI  - Evaluation of indoor radon measurements in Hungary.
AB  - The RAD Laboratory measured annual means of radon activity concentrations in 15
      277 first-floor rooms of dwellings and in 325 rooms on upper floors in Hungary
      (1994-2004). The original purpose of the survey was to find radon-prone area in
      Hungary. The maximum measured value was 5800 Bq m(-3), while the minimum was 10
      Bq m(-3). Due to geological diversity and different structures of buildings, the
      data set of first-floor rooms did not follow the lognormal distribution.
      Therefore, strata were chosen so that the measured data fitted the lognormal
      distribution. The numbers of dwellings above a given radon level were determined
      in each stratum. The national distribution was then taken as the sum of the
      individual distributions of all strata. This distribution was not lognormal. The
      parameters of the best fitting lognormal distribution were GM = 58 Bq m(-3), GSD
      = 2.2. The weighted averages of strata values GM = 62 Bq m(-3), GSD=2.1 were
      obtained corresponding to 92% of Hungarian dwellings.

PMID- 16581165
TI  - Assessment of radiation exposure in the uranium mining and milling area of Mailuu
      Suu, Kyrgyzstan.
AB  - The area of the town of Mailuu Suu, Kyrgyzstan, is polluted by radionuclides and
      heavy metals from tailing dumps and heaps resulting from the historic
      exploitation of uranium mines. In the frame of a European Commission-TACIS funded
      project, radiological assessment was performed for critical group members living
      in the city of Mailuu Suu, located downstream the tailings, or in the village of
      Kara Agach, partially located on a uranium mine waste dump. The actual external
      exposure is around 1.2 mSv a(-1) at both locations and exposure from radon is
      around 3 mSv a(-1) at Mailuu Suu and around 10 mSv a(-1) at Kara Agach. Ingestion
      dose was negligible for a critical group member living at Mailuu Suu. At Kara
      Agach, however, under the hypothesis that all food and fodder is cultivated
      locally, exposure from ingestion is much higher ( approximately 10-30 mSv a(-1)).
      In case of an accidental scenario [(part of) Tailing 3 content thrust to river],
      estimated additional maximum doses result in 45 and 77 mSv for an adult and a
      child, respectively.

PMID- 16581166
TI  - Atmospheric deposition of 137Cs between 1994 and 2002 at Cienfuegos, Cuba.
AB  - Levels of 137Cs in total atmospheric deposition have been measured in the
      Cienfuegos region (Cuba) between 1994 and 2002. Samples were collected every
      three months, evaporated to dryness to obtain residual samples, and measured by
      gamma spectrometry. The 137Cs mean concentration in total deposition was 0.24 Bq
      m(-2) and data ranged between < 0.05 and 0.62 Bq m(-2). Precipitation rates and
      raintime have proved to be the most important factors controlling the
      concentration and depositional flux of 137Cs in the atmosphere over Cienfuegos,
      showing a high correlation coefficient (R = 0.93).

PMID- 16581167
TI  - Polybrominated diphenyl ethers in surface sediments of the Yangtze River Delta:
      Levels, distribution and potential hydrodynamic influence.
AB  - A total of 32 surface sediments collected from the Yangtze River Estuary,
      Hangzhou Bay and the Qiantang River were analyzed for polybrominated diphenyl
      ethers (PBDEs). The concentrations of summation operatorPBDEs (sum of 12 PBDE
      congeners without BDE 209) and BDE 209 varied from n.d. to 0.55 and from 0.16 to
      94.6 ng/g, respectively. The spatial variability of summation operatorPBDEs
      concentrations indicated that waste discharge from the urban areas might been the
      main source of PBDEs in the Yangtze River Delta. BDE 209 was the predominant
      congener (approximately 90-100%) detected among the 13 congeners, consistent with
      the fact that technical deca-BDE mixtures are presently the dominant technical
      PBDE mixtures used in China. Compared to published data acquired from other
      locales, PBDE congeners with less than four bromines were more abundant in the
      present study area. The hydrodynamic conditions may likely be a significant
      factor in dictating the observed levels and congener distribution patterns of
      PBDEs.

PMID- 16581168
TI  - Effect of unpleasant loud noise on hippocampal activities during picture
      encoding: an fMRI study.
AB  - The functional link between the amygdala and hippocampus in humans has not been
      well documented. We examined the effect of unpleasant loud noise on hippocampal
      and amygdaloid activities during picture encoding by means of fMRI, and on the
      correct response in humans. The noise reduced activity in the hippocampus during
      picture encoding, decreased the correct response and increased the activity of
      the amygdala. A path diagram using structural equation modeling suggested that
      hippocampus activity might be depressed by high amygdala activity. Therefore,
      noise should diminish memory by reducing hippocampal activity, which might be
      depressed by high amygdala activity.

PMID- 16581169
TI  - Efficacy of perospirone in the management of aggressive behavior associated with
      dementia.
AB  - We assessed the efficacy of the serotonin dopamine antagonist, perospirone (PER)
      on aggressive and agitated behavior in demented patients. Eighteen outpatients
      with dementia diagnosed according to the DSM-IV were enrolled in this study, and
      their behavioral symptoms and cognitive impairments were assessed with the
      Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) and Mini-Mental State
      Examination (MMSE) instruments for a period of 6 weeks. The maximum benefit of
      PER was achieved at a mean dose of 7.4 mg/day. Post-hoc analysis showed
      significant improvement in verbal outbursts after 4 weeks and in agitation scores
      after 4 and 6 weeks. Only 2 patients dropped out of the study, because of adverse
      effects, and no serious adverse effect was observed. The data suggest that PER is
      effective in improving aggressive and agitated behavioral symptoms in demented
      patients and that it is safe to use in elderly patients.

PMID- 16581170
TI  - Ziprasidone in the treatment of delayed carbon monoxide encephalopathy.
AB  - Delayed carbon monoxide (CO) encephalopathy is a serious complication of acute CO
      poisoning. We present a case of successful treatment of ziprasidone, a newer
      atypical antipsychotic, in delayed CO encephalopathy. A 52-year-old depressed
      woman suffered acute CO intoxication after an attempt of suicide by burning
      charcoal. She was initially treated with hyperbaric oxygen (HBO) therapy for the
      acute intoxication. One week later, the patient developed neuropsychiatric
      symptoms including parkinsonism, tardive dyskinesia (TD), cognitive
      deterioration, urinary incontinence, gait disturbance, mutism, disorientation to
      time, place and person, and disorganized as well as disturbing behavior. During
      her psychiatric hospitalization, the patient had been treated with daily HBO
      therapy, bromocriptine (2.5 mg/day), the conventional antipsychotic sulpiride
      (600 mg/day), and atypical antipsychotics such as risperidone (5 mg/day) and
      quetiapine (400 mg/day). However, her delayed neuropsychiatric sequelae of CO
      intoxication persisted despite of these treatments. It was until she had been
      treated with ziprasidone (80 mg/day) for 10 days that her mental condition was
      improved. With ziprasidone therapy, the patient obtained substantial improvement
      in her neuropsychiatric symptoms, cognitive function, and daily activities. Our
      case indicates that ziprasidone can be used effectively in the treatment of
      delayed CO encephalopathy.

PMID- 16581171
TI  - New-onset type-2 diabetes associated with atypical antipsychotic medications.
AB  - PURPOSE: This study compared the one-year incidence of new-onset type-2 diabetes
      mellitus (DM) and changes in weight in patients with a variety of psychiatric
      diagnoses prescribed olanzapine, risperidone, or quetiapine, compared to a
      reference group receiving haloperidol and no other antipsychotic medication.
      RESEARCH DESIGN AND METHODS: Data was abstracted from charts of subjects newly
      initiated and then maintained for one year on olanzapine (n=112), risperidone
      (n=100), quetiapine (n=100), and haloperidol (n=100). Baseline and one-year DM
      status, height, and weight were collected, as well as concurrent psychotropic
      medications, medical and psychiatric comorbidities. FINDINGS: Using a
      multivariate model, logistic regression identified a significant association
      between olanzapine (but not other atypical agents) and the development of
      diabetes compared to haloperidol over the one-year period (odds ratio 8.4, 95% CI
      1.8-38.7). Baseline obesity was independently associated with new-onset DM, but
      only marginally greater weight gain was found among olanzapine users.
      CONCLUSIONS: The middle-aged American veterans in this study cohort were highly
      vulnerable to the diabetogenic effects of olanzapine, but a close correlation
      with weight change was not found. Patients administered olanzapine should receive
      careful laboratory monitoring for elevated plasma glucose in addition to weight
      measurement.

PMID- 16581173
TI  - [Compound tissue reconstruction of the forearm in emergency. About 17 clinical
      cases].
AB  - The authors report a serial of 17 patients with complex trauma of the forearm
      treated in emergency by means of compound tissue reconstruction. Every patient
      present a cutaneous defect associated with multiple lesions or defects of the
      subjacent tissues. The management consisted of a large debridement with excision
      of all contuse tissues, a stable osteosynthesis witch permit an early
      mobilization of the hand and fingers, a revascularization of the hand by a by
      pass procedure or a vascular bridge free flap, reconstruction of the muscles,
      tendons, and the nerves at the same time as possible, a coverage of the tissues
      by free flaps or forearm pedicle flaps and a physiotherapy by a specialized team
      undertaken immediately after surgery. The functional results have been evaluated
      satisfying in the whole serial. The authors conclude that the compound tissue
      reconstruction of the forearm in emergency with an early physiotherapy permits an
      optimal functional recovery within short period. It authorizes a rapid
      socioprofessional return of these patients with complex trauma of the forearm.

PMID- 16581172
TI  - Brain-derived neurotrophic factor gene (BDNF) variants and schizophrenia: an
      association study.
AB  - Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene have been
      suggested to be associated with schizophrenia. In a replication attempt, Swedish
      patients with schizophrenia (n=187) and control subjects (n=275) were assessed
      for four BDNF gene polymorphisms. There were no significantly different allele,
      genotype or haplotype frequencies between cases or controls. Neither were there
      any differences when schizophrenic patients were sub-divided with regard to a
      number of different clinical variables, although a small group of psychotic
      patients with prominent affective features displayed higher frequencies of the
      less common alleles of the Val66Met and 11757 G/C polymorphisms compared to
      controls. The present Swedish results do not verify previous associations between
      putative functional BDNF gene polymorphisms and schizophrenia. However, when
      combined with previous studies meta-analyses indicated that the BDNF 270 T-allele
      and the Val66Met homozygous state were associated with the disorder. Thus, the
      BDNF gene may confer susceptibility to schizophrenia. Additional studies are
      warranted to shed further light on this possibility.

PMID- 16581174
TI  - The physical-mechanical performance of the new Ketac Molar Easymix compared to
      commercially available glass ionomer restoratives.
AB  - OBJECTIVES: To evaluate the time dependence of physical-mechanical performance of
      glass ionomer restoratives. METHODS: The physical-mechanical properties of Ketac
      Molar Easymix in comparison to four handmix glass ionomer restoratives were
      evaluated by testing the compressive and flexural strength, acid erosion and
      solubility. By testing the properties in the early and late setting phase it was
      determined how fast the level of material characteristics is achieved. IR
      spectroscopy was used for monitoring the acid-base reaction. RESULTS: The
      compressive strength after 1 and 24h setting time show that Ketac Molar Easymix
      and Fuji IX demonstrate a significantly higher performance. Ketac Molar Easymix
      exhibits by far the highest flexural strength 1h after start of setting. After
      24h, it remains at this high level and only Vitro Molar and Fuji IX come close.
      Ketac Molar Easymix and Fuji IX show the lowest solubility in neutral media after
      24h and 7d. It is remarkable that the solubilities of Ionofil Molar, Vitro Molar
      and Vidrion R stored in water for 24h are higher than those of Ketac Molar
      Easymix and Fuji IX obtained after 7d water immersion. In acidic media Ketac
      Molar Easymix is least prone to acid erosion. CONCLUSIONS: For clinical success
      of a filling material the early achievement of a high physical-mechanical
      performance is mandatory to minimize the risk of early damage to a restoration.
      With the high flexural strength reached after 1h combined with the lowest
      susceptibility for acid-attack and solubility in water, Ketac Molar Easymix, from
      3M ESPE, provides the best performance of any materials tested.

PMID- 16581175
TI  - The ribosomal A-site as an inspiration for the design of RNA binders.
AB  - The specific binding of aminoglycoside antibiotics to the bacterial ribosomal
      decoding site (A-site) has inspired the study of RNA-small molecules interactions
      and the search for novel RNA binders. Among the numerous RNA targets studied so
      far, the A-site holds a unique place. It is among the few truly validated RNA
      targets for which naturally occurring ligands have been discovered as "cognate"
      binders. In addition, due to its encapsulating architecture, the A-site is a more
      discriminating RNA target when compared to other RNA sequences. Previous
      observations and current challenges for the designers of potent and specific RNA
      binders are discussed.

PMID- 16581176
TI  - Autoreduction and aggregation of fungal laccase in solution phase: possible
      correlation with a resting form of laccase.
AB  - This paper reports results of a reexamination of some poorly understood
      peculiarities of laccases, an enzyme family which has been extensively studied in
      our laboratories as well as by others for some years. The issue that is
      reconsidered here is the previously proposed existence of "active" and "resting"
      forms of laccases. The presence of fungal laccases with partly reduced active
      sites is demonstrated. Of further interest is that an aggregated state in
      solution, not to our knowledge previously noted for laccase, has been found by
      using small-angle X-ray scattering as well as thorough analysis of the results of
      several biochemical experiments. Under some conditions, this aggregated state may
      correlate with the resting form of the laccases, although this resting form could
      have a broader significance. It was shown that Trametes ochracea laccase had some
      anomalous characteristics, which could be correlated with the high concentration
      of the "resting" enzyme. The mechanism of formation of resting laccase is
      suggested. Knowledge of the resting state is of importance for in vitro studies.
      Additionally, a suggestion about the possible regulatory role of this form in
      vivo is mentioned.

PMID- 16581178
TI  - Formal agent-based modelling of intracellular chemical interactions.
AB  - Individual-based or agent-based models have proved useful in a variety of
      different biological contexts. This paper presents an agent-based model using a
      formal computational modelling approach to model a crucial biological system--the
      intracellular NF-kappaB signalling pathway. The pathway is vital to immune
      response regulation, and is fundamental to basic survival in a range of species.
      Alterations in pathway regulation underlie many diseases, including
      atherosclerosis and arthritis. Our modelling of individual molecules, receptors
      and genes provides a more comprehensive outline of regulatory network mechanisms
      than previously possible with equation-based approaches. The model has been
      validated with data obtained from single cell experimental analysis.

PMID- 16581177
TI  - Molecular cloning and functional characterization of two isoforms of
      dermonecrotic toxin from Loxosceles intermedia (brown spider) venom gland.
AB  - Brown spider (Genus Loxosceles) bites are normally associated with necrotic skin
      degeneration, gravitational spreading, massive inflammatory response at injured
      region, platelet aggregation causing thrombocytopenia and renal disturbances.
      Brown spider venom has a complex composition containing many different toxins, of
      which a well-studied component is the dermonecrotic toxin. This toxin alone may
      produce necrotic lesions, inflammatory response and platelet aggregation.
      Biochemically, dermonecrotic toxin belongs to a family of toxins with 30-35 kDa
      characterized as sphingomyelinase-D. Here, employing a cDNA library of Loxosceles
      intermedia venom gland, we cloned and expressed two recombinant isoforms of the
      dermonecrotic toxin LiRecDT2 (1062 bp cDNA) and LiRecDT3 (1007 bp cDNA) that
      encode for signal peptides and complete mature proteins. Phylogenetic tree
      analysis revealed a structural relationship for these toxins compared to other
      members of family. Recombinant molecules were expressed as N-terminal His-tag
      fusion proteins in Escherichia coli and were purified to homogeneity from cell
      lysates by Ni(2+) chelating chromatography, resulting in proteins of 33.8 kDa for
      LiRecDT2 and 34.0 kDa for LiRecDT3. Additional evidence for related toxins
      containing sequence/epitopes identity comes from antigenic cross-reactivity using
      antibodies against crude venom toxins and antibodies raised with a purified
      dermonecrotic toxin. Recombinant toxins showed differential functionality in
      rabbits: LiRecDT2 caused a macroscopic lesion with gravitational spreading upon
      intradermal injection, while LiRecDT3 evoked transient swelling and erythema upon
      injection site. Light microscopic analysis of skin biopsies revealed edema, a
      collection of inflammatory cells in and around blood vessels and a proteinaceous
      network at the dermis. Moreover, differential functionality for recombinant
      toxins was also demonstrated by a high sphingomyelinase activity for LiRecDT2 and
      low activity for LiRecDT3 as well as greater in vitro platelet aggregation and
      blood vessel permeability induced by LiRecDT2 and residual activity for LiRecDT3.
      Cloning and expression of two recombinant dermonecrotic toxins demonstrate an
      intraspecific family of homologous toxins that act in synergism for deleterious
      activities of the venom and open possibilities for biotechnological applications
      for recombinant toxins as research tools for understanding the inflammatory
      response, vascular integrity and platelet aggregation modulators.

PMID- 16581179
TI  - T3 strongly regulates GLUT1 and GLUT3 mRNA in cerebral cortex of hypothyroid rat
      neonates.
AB  - Experimental hypothyroidism alters the expression of the GLUT1 and GLUT4 glucose
      transporters in brown adipose tissue, skeletal muscle and heart. Congenital
      hypothyroidism disrupts the development and function of the CNS, and the
      importance of GLUT1 for proper brain function has been dramatically evidenced in
      the cases of GLUT1 deficiency syndrome. Because of this, we hypothesised that the
      expression of GLUT1 and GLUT3, glucose transporters expressed in brain cortex,
      may be altered in congenital hypothyroidism. GLUT3 mRNA was induced during
      postnatal development whereas GLUT1 mRNA was initially repressed and further
      induced; both processes were essentially similar in control and hypothyroid
      animals. Under these conditions GLUT1 protein expression was reduced in cerebral
      cortex from 15-day-old hypothyroid neonates, which suggests the existence of post
      transcriptional alterations. The most striking differences were observed when
      hypothyroid animals at different developmental stages were treated acutely with
      T(3). GLUT1 and GLUT3 mRNA expression behaved in opposite ways in response to
      treatment with the hormone. Furthermore, the behaviour of each glucose
      transporter isoform against T(3) was not uniform but changed alongside
      development. In all, our data show that the regulation of GLUT1 and GLUT3 in
      cerebral cortex is regulated by T(3) in a complex way and suggest that
      alterations in the expression of glucose transporters induced by hypothyroidism
      might have a functional impact on brain glucose uptake.

PMID- 16581181
TI  - Effect of metals and phenylalanine on the activity of human tryptophan
      hydroxylase-2: comparison with that on tyrosine hydroxylase activity.
AB  - We cloned the human tryptophan hydroxylase-2 (hTPH2) gene by RT-PCR, and
      expressed and purified its product as a maltose-binding protein (MBP)-fusion
      protein. We investigated the effects of essential divalent cations and L
      phenylalanine (L-Phe) on the hTPH2 activity for the first time, and compared them
      with those on human tyrosine hydroxylase (hTH1) activity. We found that cobaltous
      and manganous ions inhibited the activities of both enzymes but that hTH1 was
      affected at lower concentrations than hTPH2. From kinetic analyses, we found that
      phenylalanine acted as an inhibitor more strongly against hTPH2 than against
      hTH1. These data are important for elucidating the molecular mechanism underlying
      the alterations in the contents of serotonin and catecholamines in the brain
      under pathological and physiological conditions, such as hyperphenylalaninemia
      and chronic manganese toxicity.

PMID- 16581180
TI  - Endothelin-1 promotes cell survival in renal cell carcinoma through the ET(A)
      receptor.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor that has been shown to
      significantly impact many benign and malignant tissues by signaling through its
      two cognate receptors: ET(A) and ET(B). As ET-1 has a role in both normal and
      diseased kidney, we initiated studies to investigate endothelin axis expression
      and function in renal cell carcinoma (RCC). In this study, relatively high levels
      of ET-1 were detected in all six human RCC cell lines investigated. RT-PCR and
      Southern analyses revealed that all six RCC cell lines expressed ET(A) receptor
      mRNA, while 3/6 cell lines also expressed ET(B) mRNA. High affinity ET-1 binding
      occurred in all but one RCC cell line and quantitative RT-PCR demonstrated ET(A)
      mRNA expression in all six cell lines. Methylation of the ET(B) promoter (EDNRB)
      in 4/6 RCC cell lines was observed, suggesting a mechanism for repressed ET(B)
      expression. Moreover, methylation occurred in 32/48 of renal tumors and in 27/55
      of histologically normal adjacent tissue samples studied, while no methylation
      was evident in any normal tissue isolated from nephrectomy or at autopsy.
      Functionally, ET-1 significantly inhibited paclitaxel-induced apoptosis in RCC
      cells through binding ET(A) with the ET-1 signaling mediated via the PI3
      kinase/Akt pathway. Collectively, these data support the therapeutic targeting of
      the ET(A) receptor as a novel treatment strategy for RCC.

PMID- 16581182
TI  - Light-induced Fos expression is attenuated in the suprachiasmatic nucleus of
      serotonin 1B receptor knockout mice.
AB  - The hypothalamic suprachiasmatic nucleus (SCN) is a circadian oscillator that
      receives a dense serotonergic innervation from the median raphe nucleus.
      Serotonin (5-HT) modulates the effects of light on circadian behavior by acting
      on 5-HT1B receptors on retinohypothalamic (RHT) terminals in the SCN. Activation
      of 5-HT1B presynaptic receptors on RHT terminals inhibits glutamate release.
      However, 5-HT1B receptor knockout (5-HT1B KO) mice have attenuated behavioral
      responses to light [P.J. Sollars, M.D. Ogilvie, A.M. Simpson, G.E. Pickard,
      Photic entrainment is altered in the 5-HT1B receptor knockout mouse, J. Biol.
      Rhythms 21 (2006) 21-32]. To assess the cellular response of the 5-HT1B KO SCN to
      light, light-induced Fos expression was analyzed in 5-HT1B KO and wild-type (WT)
      mice. In addition, the distribution of melanopsin containing retinal ganglion
      cells that contribute the majority of axons to the RHT was examined in 5-HT1B KO
      mice and compared to that of WT mice. Light-induced Fos expression in the SCN was
      reduced in 5-HT1B KO mice compared to WT mice at circadian time (CT) 16 and CT 23
      in a manner similar to the reduction previously described in light-induced
      behavioral phase shifts. The number of melanopsin retinal ganglion cells was
      similar in WT and 5-HT1B KO mice. These data taken together with previous data
      suggest that functional removal of the 5-HT1B receptor results in reduced
      functional light input to the SCN.

PMID- 16581183
TI  - Reversal by phosphodiesterase-4 blockers of in vitro apnea in the isolated
      brainstem-spinal cord preparation from newborn rats.
AB  - Ventilation of the lungs is mediated by neurons of the respiratory network in the
      lower brainstem. The activity of rhythmogenic respiratory network neurons seems
      to depend greatly on cellular levels of the second messenger cAMP. Accordingly,
      depression of breathing in (preterm) infants associated with clinical
      administration of opioids and prostaglandins results likely from a fall of cAMP
      in these cells caused by G(i/o) proteins that are activated via mu-opiate or
      EP(3) prostanoid receptors, respectively. Typically, such drug-induced depression
      of infant breathing is treated with high doses of methylxanthines that have
      notable adverse effects. It was the aim of our study to investigate whether
      clinically applicable blockers of cAMP-hydrolyzing phosphodiesterase-4 counteract
      the inhibition of the respiratory network associated with a drug-induced fall of
      cAMP. For this purpose, inspiratory-related cervical nerve activity was measured
      in isolated brainstem-spinal cord preparations from newborn rats. Respiratory
      frequency was depressed by >80% (from >5 bursts/min to <1 burst/min) with
      nociceptin (1 microM) which decreases cAMP via a G(i/o) protein-coupled opioid
      like receptor. The nociceptin-induced respiratory depression was reversed by the
      activator of adenylyl cyclase, forskolin (5-25 microM) and the phosphodiesterase
      4 blockers rolipram (0.1-1 microM) and RO-201724 (1-5 microM). Blocking
      phosphodiesterases 3 and 5 with milrinone (25-100 microM) and zaprinast (25-100
      microM), respectively, was not effective. The results indicate that
      phosphodiesterase-4 blockers are strong stimulants of the respiratory network. We
      hypothesize that these or related agents may be potent tools for a treatment of
      drug-induced disturbances of breathing in (preterm) infants.

PMID- 16581184
TI  - Age-related severity of dopaminergic neurodegeneration to MPTP neurotoxicity
      causes motor dysfunction in C57BL/6 mice.
AB  - This study investigated the influence of advancing age on dopaminergic neuronal
      degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      intoxication from the perspective concerning the relationship between
      dopaminergic function and behavioral features. Young (10 weeks) and older (14-15
      months) C57BL/6 mice were treated with one to four injections of MPTP (20 mg/kg
      at 2h intervals). Although young mice showed no mortality in either MPTP
      treatment, older mice exhibited mortality from only two injections of MPTP during
      the experimental period. An extensive dopaminergic cell loss was found in both
      the striatum and substantia nigra of older mice given one and two injections of
      MPTP with marked decrease in striatal dopamine (DA) levels, but not young mice.
      We also found a behavioral change in the tail suspension test associated with the
      extent of decrease in striatal DA levels in MPTP-treated older mice, but not in
      young mice. These results clearly present age-related vulnerability to MPTP
      neurotoxicity in C57BL/6 mice and strongly support our previous report showing
      that there is a critical threshold level of the decrement in striatal DA contents
      causing motor dysfunction in this mouse model of Parkinson's disease.

PMID- 16581185
TI  - Nobiletin restoring beta-amyloid-impaired CREB phosphorylation rescues memory
      deterioration in Alzheimer's disease model rats.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      characterized by cognitive and memory deterioration. Production and accumulation
      of beta-amyloid peptide (Abeta) is central to the pathogenesis of AD. Recent
      studies have demonstrated that PKA/CREB-dependent signaling pathway and long-term
      potentiation are inhibited by sublethal concentrations of Abeta(1-42) in cultured
      hippocampus neurons. Here, we examined the effects of nobiletin on the Abeta
      induced inhibition of CREB phosphorylation in cultured rat hippocampus neurons. A
      sublethal concentration of Abeta(1-42) or Abeta(1-40) decreased glutamate-induced
      CREB phosphorylation, whereas pretreatment with nobiletin reversed the Abeta
      induced decrease in CREB phosphorylation. The effects of nobiletin on impairment
      of learning ability were also examined in chronically Abeta(1-40) infused AD
      model rats using the eight-arm radial maze. In the AD model rats, nobiletin
      showed protective effects on Abeta(1-40)-induced impairment of learning ability.
      These results suggest that nobiletin has the potential for becoming a novel lead
      compound for drug development for AD.

PMID- 16581187
TI  - Branching mode in complex-type triantennary N-glycans as regulatory element of
      their ligand properties.
AB  - We address the question whether the two natural types of branching in complex
      type triantennary N-glycans differ in ligand properties. Toward this end, we
      prepared the set of pergalactosylated undecasaccharides and derivatives with
      alpha2,3/6-sialylation by chemoenzymatic synthesis. Conjugation resulted in
      neoglycoproteins which were tested in assays with lectins/antibodies, cultured
      cells and animals. Solid-phase assays with galactoside-specific proteins (a plant
      toxin, galectins and an antibody fraction) disclosed that the branching mode did
      not significantly affect affinity. However, compared to previous studies under
      identical conditions increase in antennae number and presence of substitutions in
      biantennary N-glycans altered KD-values with differences between receptors.
      Neoglycoprotein binding to cells of eight human tumor lines was sensitive to N
      glycan branching. Staining intensity revealed pronounced branch-mode-dependent
      differences in four cases. Biodistribution profiles in mice uncovered dramatic
      changes in clearance rates with prolonged serum presence associated with type II
      branching of sialylated N-glycans and markedly increased uptake of
      neoglycoproteins with type I-branched N-glycans into liver, spleen, heart and
      lungs. This part of the study is relevant for rational glycoengineering of
      pharmaproteins. In general, our study supports the concept to view details of N
      glycan structure, here branching, as a means to modulate ligand properties.

PMID- 16581186
TI  - Augmented cocaine-induced accumbal dopamine efflux, motor activity and place
      preference in rats fed with a tryptophan-deficient diet.
AB  - In the present study we demonstrate that consumption of a tryptophan-deficient
      diet for a period of 14 days decreased the striatal serotonin and 5
      hydroxyindolacetic acid tissue content in rats, whereas the level of dopamine
      remained unchanged. Under this condition of diminished serotonergic tone, a
      challenge dose of cocaine (10mg/kg, i.p.) significantly increased motor activity
      and dopamine extracellular content in the nucleus accumbens compared to rats fed
      with a balanced diet. We moreover found that pretreatment with cocaine (7 and
      10mg/kg, i.p.) produced a significant increase in preference for a cocaine
      associated environment in the tryptophan-deficient group compared to control
      rats. Our experiments show that a low tone of serotonergic system, augments the
      behavioural reinforcing effect of cocaine and that this effect may be due to a
      increased cocaine-induced accumbal dopamine release. These data indicate that a
      tryptophan-deficient diet alters the behavioural and neurochemical effect of
      psychostimulants, such as cocaine, and suggest an important role of serotonin in
      modulation of these effects.

PMID- 16581189
TI  - Decline in hippocampal theta activity during cessation of locomotor approach
      sequences: amplitude leads frequency and relates to instrumental behavior.
AB  - Hippocampal theta frequency and amplitude decrease as locomotor approach slows
      and the goal is reached. This study compared the declines of these theta
      parameters and related them to behavioral events. Theta activity was recorded
      with bipolar electrodes spanning cornu Ammon, sector 1 or cornu Ammon, sectors
      2/3 cell layers of the dorsal hippocampus in 12 rats trained to approach and
      depress a treadle which exposed a milk dipper. Behavioral events were identified
      using a video capture system (20-ms sampling) synchronized to the hippocampal
      recording system (10-ms sampling). Peri-event averages of theta activity were
      made around the initial paw contact with the treadle, the presentation of the
      dipper, and the first lick at the dipper. Phase relationships between averaged
      hippocampal slow wave activity and behavioral events occasionally were found but
      they were inconsistent. In averages of both amplitude and frequency, times of
      minimum were less variable around paw contact indicating that compared with
      reward presentation and consummatory behavior, it more closely related to the
      processes determining the declines. Theta amplitude declined more rapidly than
      frequency and reached an earlier minimum in averages around initial paw contact
      and dipper presentation. Mean amplitude minimum occurred after the paw contact at
      159 ms but the decline of frequency continued into the licking bout with its
      minimum occurring at 343 ms. The findings indicate that during the termination of
      approach locomotion, the amplitude of hippocampal theta activity is closely
      related to specific expected sensorimotor events.

PMID- 16581188
TI  - A new dinuclear biphenylene bridged copper(II) complex: DNA cleavage under
      hydrolytic conditions.
AB  - The dinucleating ligand, tpbpd (tetrapyridyl biphenylenediamine) forms a dicopper
      complex with practically no electronic coupling between the two copper (II)
      centres. The EPR spectrum of the complex is consistent with coordination of each
      copper ion to two nitrogens of the binuclear ligand. Cyclic voltammogram of the
      complex also reveals that the two copper (II) centres have identical ligating
      environment. This dimeric copper (II) complex is found to be a very efficient
      catalyst for the cleavage of plasmid DNA in the absence of any added cofactor.
      The amount of conversion of supercoiled form (Form I) of plasmid to the open
      circular form (Form II) depends on the concentration of the complex as well as
      the duration of incubation of the complex with DNA. The maximum rate of
      conversion of the supercoiled form to the nicked circular form at pH 7.5 in the
      presence of 150 microM of the complex is found to be 1.8 x 10(-3) s(-1).

PMID- 16581190
TI  - Gender differences in long-term beneficial effects of erythropoietin given after
      neonatal stroke in postnatal day-7 rats.
AB  - Recently, we reported that erythropoietin attenuates neonatal brain injury caused
      by focal cerebral ischemia. The long-term effects of erythropoietin on focal
      cerebral ischemia-induced injury to the developing brain and the potential gender
      differences in these long-term effects have not been studied in detail. The
      current study demonstrated a similarity in the mean infarct volume in both the
      vehicle-treated male and female rats at 6 and 12 weeks after focal cerebral
      ischemia. On the other hand, erythropoietin treatment (1000 U/kg x three doses
      after focal cerebral ischemia) caused a significant reduction in the mean infarct
      volume in both males and females at 6 weeks after focal cerebral ischemia when
      compared with the corresponding vehicle-treated animals (males: 141.4+/-48.2 mm3
      vs. 194.0+/-59.2 mm3, P<0.05; females: 85.4+/-31.6 mm3 vs. 183.4+/-46.3 mm3,
      P<0.05). Interestingly, the reduction in the mean infarct volume in the
      erythropoietin-treated males was significantly less than that in the
      erythropoietin-treated females at 6 weeks after focal cerebral ischemia (141.4+/
      48.2 mm3 vs. 85.4+/-31.6 mm3, P<0.05). At 12 weeks after focal cerebral ischemia,
      the mean infarct volume in the erythropoietin-treated males significantly
      increased to 181.0+/-50.4 mm3 (P<0.05). In contrast, the mean infarct volume in
      the erythropoietin-treated females remained stable (87.0+/-41.7 mm3).
      Additionally, erythropoietin treatment significantly improved sensorimotor
      function recovery with a misstep number similar to the sham-operation group at 6
      and 12 weeks after focal cerebral ischemia. Moreover, the mean number of missteps
      in the erythropoietin-treated females was less than that in males at 6 (13.5+/
      2.0 vs. 24.5+/-2.5, P<0.05) and 12 (12.5+/-2.0 vs. 20.0+/-2.0, P<0.05) weeks
      after focal cerebral ischemia. These results indicate that erythropoietin
      administration after focal cerebral ischemia produces a significant long-term
      neuroprotective benefit on the developing brain, and that this effect is more
      beneficial in the female rats.

PMID- 16581191
TI  - Nitric oxide-mediated mechanism of neuronal nitric oxide synthase and inducible
      nitric oxide synthase expression during hypoxia in the cerebral cortex of newborn
      piglets.
AB  - Previously, we have shown that hypoxia results in increased generation of nitric
      oxide free radicals in the cerebral cortex of newborn piglets that may be due to
      up-regulation of nitric oxide synthases, neuronal nitric oxide synthase and
      inducible nitric oxide synthase. The present study tests the hypothesis that
      hypoxia results in increased expression of neuronal nitric oxide synthase and
      inducible nitric oxide synthase in the cerebral cortex of newborn piglets and
      that the increased expression is nitric oxide-mediated. Newborn piglets, 2-4 days
      old, were divided to normoxic (n=4), hypoxic (n=4) and hypoxic-treated with 7
      nitro-indazole-sodium salt, a selective neuronal nitric oxide synthase inhibitor
      (hypoxic-7-nitro-indazole-sodium salt, n=6, 1 mg/kg, 60 min prior to hypoxia).
      Piglets were anesthetized, ventilated and exposed to an FiO2 of 0.21 or 0.07 for
      60 min. Cerebral tissue hypoxia was documented biochemically by determining ATP
      and phosphocreatine. The expression of neuronal nitric oxide synthase and
      inducible nitric oxide synthase was determined by Western blot using specific
      antibodies for neuronal nitric oxide synthase and inducible nitric oxide
      synthase. Protein bands were detected by enhanced chemiluminescence, analyzed by
      imaging densitometry and the protein band density expressed as absorbance (OD x
      mm(2)). The density of neuronal nitric oxide synthase in the normoxic, hypoxic
      and hypoxic-7-nitro-indazole-sodium salt groups was: 41.56+/-4.27 in normoxic,
      61.82+/-3.57 in hypoxic (P<0.05) and 47.80+/-1.56 in hypoxic-7-nitro-indazole
      sodium salt groups (P=NS vs normoxic), respectively. Similarly, the density of
      inducible nitric oxide synthase in the normoxic, hypoxic and hypoxic-7-nitro
      indazole-sodium salt groups was: 105.21+/-9.09, 157.71+/-13.33 (P<0.05 vx
      normoxic), 117.84+/-10.32 (p=NS vx normoxic), respectively. The data show that
      hypoxia results in increased expression of neuronal nitric oxide synthase and
      inducible nitric oxide synthase proteins in the cerebral cortex of newborn
      piglets and that the hypoxia-induced increased expression is prevented by the
      administration of 7-nitro-indazole-sodium salt. Furthermore, the neuronal nitric
      oxide synthase inhibition prevented the inducible nitric oxide synthase
      expression for a period of 7 days after hypoxia. Since administration of 7-nitro
      indazole-sodium salt prevents nitric oxide generation by inhibiting neuronal
      nitric oxide synthase, we conclude that the hypoxia-induced increased expression
      of neuronal nitric oxide synthase and inducible nitric oxide synthase is mediated
      by neuronal nitric oxide synthase derived nitric oxide. We speculate that during
      hypoxia nitric oxide-mediated up-regulation of nitric oxide synthases will
      continue the perpetual cycle of nitric oxide generation-->NOS up-regulation-
      >nitric oxide generation resulting in hypoxic neuronal death.

PMID- 16581192
TI  - The tripeptide phenylalanine-(D) glutamate-(D) glycine modulates leukocyte
      infiltration and oxidative damage in rat injured spinal cord.
AB  - The tripeptide, phenylalanine-glutamate-glycine (FEG) and its d-isomeric form
      phenylalanine-(D) glutamate-(D) glycine (feG), derived from submandibular gland
      peptide-T, significantly reduce the allergic inflammatory response and leukocyte
      trafficking and neutrophil migration into intestine, heart and lungs. Due to
      these actions, we hypothesized that feG would attenuate the early inflammatory
      response to spinal cord injury, reduce free radical production and improve
      neurological outcomes, like other leukocyte-limiting strategies we have used
      previously. We tested this using a clip compression model of spinal cord injury
      in rats. Following spinal cord injury at the 4th thoracic cord segment, we
      quantified leukocyte infiltration, free radical formation and oxidative damage at
      the lesion site after feG or control peptide phenylalanine-(D) aspartate-(D)
      glycine treatment. In rats treated with feG at 2 and 12 h, or 6 and 12 h after
      spinal cord injury, mean myeloperoxidase activity and ED-1 expression were
      significantly lower ( approximately 40%) than in controls at 24 h. Free radical
      formation generated in injured spinal cord was detected using 2',7'
      dichlorofluorescin-diacetate as a fluorescent probe. Free radical production in
      the injured cord increased significantly after spinal cord injury and feG
      treatment significantly reduced this free radical production. Oxidative enzymes,
      lipid peroxidation and cell death were also significantly ( approximately 40%),
      gp91 ( approximately 30%), thiobarbituric acid reactive substance levels (
      approximately 35%), 4-hydroxynonenal-bound protein ( approximately 35%) and
      caspase-3 ( approximately 32%). Early administration of feG decreases
      infiltration of inflammatory cells into the injured spinal cord and intraspinal
      free radical formation, thereby reducing oxidative damage and secondary cell
      death after spinal cord injury.

PMID- 16581193
TI  - Activated double-stranded RNA-dependent protein kinase and neuronal death in
      models of Alzheimer's disease.
AB  - Neuronal death is a pathological hallmark of Alzheimer's disease. We have shown
      previously that phosphorylated double-stranded RNA-dependent protein kinase is
      present in degenerating hippocampal neurons and in senile plaques of Alzheimer's
      disease brains and that genetically down-regulating double-stranded RNA-dependent
      protein kinase activity protects against in vitro beta-amyloid peptide
      neurotoxicity. In this report, we showed that two double-stranded RNA-dependent
      protein kinase blockers attenuate, in human neuroblastoma cells, beta-amyloid
      peptide toxicity evaluated by caspase 3 assessment. In addition, we have used the
      newly engineered APP(SL)/presenilin 1 knock-in transgenic mice, which display a
      severe neuronal loss in hippocampal regions, to analyze the activation of double
      stranded RNA-dependent protein kinase. Western blots revealed the increased
      levels of activated double-stranded RNA-dependent protein kinase and the
      inhibition of eukaryotic initiation factor 2 alpha activity in the brains of
      these double transgenic mice. Phosphorylated RNA-dependent protein kinase-like
      endoplasmic reticulum-resident kinase was also increased in the brains of these
      mice. The levels of activated double-stranded RNA-dependent protein kinase were
      also increased in the brains of patients with Alzheimer's disease. At 3, 6 and 12
      months, hippocampal neurons display double stranded RNA-dependent protein kinase
      labelings in both the nucleus and the cytoplasm. Confocal microscopy showed that
      almost constantly activated double-stranded RNA-dependent protein kinase co
      localized with DNA strand breaks in apoptotic nuclei of CA1 hippocampal neurons.
      Taken together these results demonstrate that double-stranded RNA-dependent
      protein kinase is associated with neurodegeneration in APP(SL)/presenilin 1 knock
      in mice and could represent a new therapeutic target for neuroprotection.

PMID- 16581194
TI  - Carbachol injections into the nucleus accumbens disrupt acquisition and
      expression of fear-potentiated startle and freezing in rats.
AB  - The nucleus accumbens is involved in different types of emotional learning,
      ranging from appetitive instrumental learning to Pavlovian fear conditioning. In
      previous studies, we found that temporary inactivation of the nucleus accumbens
      blocked both the acquisition and expression of conditioned fear. This was not due
      to altered dopaminergic activity as we have also found that intra-nucleus
      accumbens infusions of the dopamine agonist amphetamine do not affect either the
      acquisition or the expression of conditioned fear. Therefore, in the present
      study we examined whether cholinergic activity in the nucleus accumbens is
      involved in the acquisition and expression of conditioned fear. Specifically, the
      effect of intra-nucleus accumbens infusions of the unselective cholinergic
      agonist carbachol on the acquisition and expression of conditioned fear was
      assessed. Across several experiments, we measured fear to visual and acoustic
      conditioned stimuli and to the experimental context. Further, two different
      measures of conditioned fear were recorded: fear potentiation of startle and
      freezing. Intra-nucleus accumbens carbachol infusions disrupted acquisition as
      well as expression of conditioned fear, regardless of the modality of the fear
      eliciting stimulus or of the specific measure of conditioned fear. This
      disruption of conditioned fear was not simply a by-product of enhanced motor
      activity which also occurred after intra-nucleus accumbens carbachol infusions.
      Interestingly, despite the substantial effect of intra-nucleus accumbens
      carbachol on expression of conditioned fear, the results of the final experiment
      suggest that these rats extinguish similarly to control rats. Taken together, the
      present results indicate that acetylcholine within the nucleus accumbens is
      important for the learning and retrieval of conditioned fear.

PMID- 16581195
TI  - Expression of fructose sensitive glucose transporter in the brains of fructose
      fed rats.
AB  - Glucose transporters play a critical role in mammalian brain energy metabolism
      because glucose is the principal brain energy source and these transporters
      promote glucose movement into neural cells. When glucose is unavailable, fructose
      can serve as an alternative energy source. Using real-time polymerase chain
      reaction and actin as a reference mRNA, we investigated the impact of fructose
      feeding on rat brain and other tissue mRNA expression of glucose transporter 5
      which has high affinity for fructose. Brain mRNA levels of glucose transporter 5
      increased 1.5-fold in 35-day old rats after 7 days of fructose feeding compared
      with controls, whereas it increased 2.5-fold in jejunum. Semi-quantitative
      analysis of protein expression by immunofluorescence of glucose transporter 5 in
      rat hippocampi indicated a 2.4-fold increase. We demonstrated the specificity of
      fructose feeding on glucose transporter 5 expression by showing that the
      expression of the neuronal glucose transporter 3 and insulin-regulated glucose
      transporter 4 were unaffected. In addition, the expression of glucose transporter
      5 increased in fructose fed older adult rats (8-months and 12-months old) when
      compared with controls. These results suggest that short-term fructose feeding
      increases the expression of glucose transporter 5 in both young and aging adult
      rats. Increased brain expression of glucose transporter 5 is likely to be
      important in the role of fructose as an alternative energy source.

PMID- 16581196
TI  - Molecular identification of an N-type Ca2+ channel in saccular hair cells.
AB  - We report new molecular evidence for the presence of an N-type (Ca(v)2.2,
      alpha1B) voltage-gated Ca(2+) channel in hair cells of the saccular epithelium of
      the rainbow trout. The Ca(v)2.2 amino-acid sequence shows 68% and 63% identity
      compared with chick and human Ca(v)2.2, respectively. This channel reveals
      features that are characteristic of an N-type Ca(2+) channel: an omega-conotoxin
      GVIA binding domain, G(betagamma) binding regions, and a synaptic protein
      interaction site. Immunohistochemical studies with a custom antibody show that
      immunoreactivity for the Ca(v)2.2 is concentrated in the basolateral and apical
      regions of hair cells. Whereas trout brain and saccular macula express an 11
      amino-acid insert in the second G(betagamma) binding domain of the Ca(v)2.2 I-II
      loop, isolated hair cells appear not to express this variant. We constructed
      fusion polypeptides representing portions of the I-II loop, beta1 and beta2a
      auxiliary subunits, the II-III loop, and syntaxin, and examined their
      intermolecular interactions via immunoprecipitation and surface plasmon
      resonance. The I-II loop polypeptides bound both beta1 and beta2a subunits with a
      preference for beta1, and the II-III loop exhibited Ca(2+)-dependent syntaxin
      binding. We demonstrated syntaxin immunoreactivity near afferent endings in hair
      cells, at hair-cell apices, and in efferent endings on hair cells, the former two
      sites consistent with binding of syntaxin to Ca(v)2.2. The present molecular
      characterization of the Ca(v)2.2 channel provides novel biochemical evidence for
      an N-type channel in hair cells, and details molecular interactions of this
      channel that reflect hair-cell function, such as spontaneous activity and
      vesicular trafficking. The current work, to our knowledge, represents the first
      demonstration of a putative N-type channel in hair cells as documented by tissue
      specific antibody immunoreactivity and hair-cell-specific cDNA sequence.

PMID- 16581197
TI  - Cognitive determinants of MDMA use among college students in Southern Taiwan.
AB  - This study was aimed to examine the Attitudes-Social influence-Efficacy Model for
      the use of MDMA among college students in Taiwan. A representative sample of 3743
      college students participated in this study. Each participant completed a
      comprehensive survey and 3090 valid data were collected. Correlation analyses
      displayed that either positive outcome expectancy or social influence was
      positively related to intention while refusal self-efficacy was negatively
      associated with intention. Using the Structural Equation Model, the results
      showed that the model fitted the data well. Intention for using MDMA affected
      MDMA use. Refusing self-efficacy significantly predicted intention and MDMA use
      indirectly via intention. Social influence had a direct impact on intention or
      MDMA use as well as an indirect effect on MDMA use via intention. However,
      positive outcome expectancy did not have an effect on both intention and the use
      of MDMA. Our results suggested that preventive programs in colleges for MDMA use
      should focus on developing strategies in decreasing the social influence and
      enhancing the refusal self-efficacy.

PMID- 16581198
TI  - Efficient inefficiency: biochemical "junk" may represent molecular bridesmaids
      awaiting emergent function as a buffer against environmental fluctuation.
AB  - The biochemical function of many parts of the genome, transcriptome, proteome,
      and interactome remain largely unknown. We propose that portions of these
      fundamental building blocks of life have no current biochemical function per se.
      Rather, sections of these "omes" may contribute to an inventory of biochemical
      parts and circuits that participate in the development of emergent functions. Low
      fidelity deoxyribonucleic acid replication, transcription, translation, and post
      translational modification all represent potential mechanisms to produce an
      inventory of parts. Stochastic processes that influence the conformations of
      ribonucleic acid molecules and proteins may also contribute to potential
      biochemical inventory. Some components of the biochemical inventory may enable
      future adaptations, some may produce disease, and some may remain useless. The
      function of many of these components await discovery, not by science, but by
      evolution. While carrying such purposeless biochemical units may appear to dilute
      fitness by exacting a thermodynamic cost, we argue that net fitness becomes
      enhanced when considering the value for potential future innovations. One can
      envision components that intermingle, interact, and act out mock pathways, but in
      most cases remain molecular bridesmaids. Given sufficiently low thermodynamic
      cost, such stochastic cycling may persist until a markedly advantageous or
      cataclysmically disadvantageous trait emerges. Maladaptive screening and
      utilization of inventory content can lead to disease phenotypes, a process
      buffered and regulated in part by the heat shock protein and stress response
      network. Whereas failure of the ubiquitin pathway to recycle misfolded proteins
      has become increasingly recognized as a source of disease, protein misfolding may
      itself represent one step in a process that maximizes functional innovation
      through increasing proteomic diversity. Fractal correlates of these processes
      occur at the organizational level of cells and organisms. That the abnormal
      accumulation of units induces local collapse may serve to limit the extension of
      damage to the greater system at large. The immune and cognitive systems that
      selectively sample and prune environmental content may serve as additional
      portals for innovation.

PMID- 16581201
TI  - Risk identification, risk assessment, and risk management of abusable drug
      formulations.
AB  - There is a demand for pharmaceutical products with reduced abuse liability. These
      products must meet three tests to be successful. They must be safe for patients,
      be less likely to injure the abuser, and be less desirable for abuse by
      established drug abusers relative to existing products on a dose for dose
      (milligram-equivalent) basis. There is a need for standardization of the
      evaluation of abusable pharmaceuticals in the various stages of drug development
      from preclinical animal studies to postmarketing surveillance. Formulations with
      reduced abuse liability must: (1) be tested using standard animal, benchtop, and
      human pharmacokinetic methods that allow interpretation, (2) sufficiently reduce
      the recovery of abusable drug substance, or contain another ingredient to deter
      abuse, (3) not alter drug activity for patients in an undesirable or risky way,
      and (4) have an accurate pre-approval estimation of their reduced abuse
      liability, which is validated by adequate epidemiologic post-approval
      surveillance.

PMID- 16581200
TI  - Latex proteins from the plant Calotropis procera are partially digested upon in
      vitro enzymatic action and are not immunologically detected in fecal material.
AB  - Soluble proteins from the latex of Calotropis procera (LP) were investigated in
      vitro and in vivo for digestibility as the latex has previously been shown to
      produce considerable toxic effects on animals. The latex is also an important
      biologically active compound that displays antiinflammatory and antidiarrhea
      properties. The proteins were digested by the action of trypsin, pepsin or
      chemotrypsin as revealed by gel filtration and SDS-PAGE analysis. Furthermore,
      the full LP digestion was easily achieved by protease treatment. Rabbit
      polyclonal antibodies raised against LP failed to detect cross-reactive molecules
      in fecal material of experimental rats following 35 consecutive days of LP
      consumption in water. Similar patterns of electrophoresis were observed for the
      negligible amounts of protein observed in the fecal extracts of control and test
      animals. No death or toxic effects were observed among animals. Taken together
      these results suggest that harmful and toxic effects on animals of the latex from
      C. procera are present in its rubber and low molecular weight fractions rather
      than its protein content.

PMID- 16581199
TI  - Risk factors for lung cancer in Iowa women: implications for prevention.
AB  - BACKGROUND: Multiple risk factors possibly associated with lung cancer were
      examined as part of a large-scale residential radon case-control study conducted
      in Iowa between 1994 and 1997. We were particularly interested in stratifying
      risk factors by smoking status. Relatively little risk factor information is
      available for Midwestern rural women. METHODS: Four hundred thirteen female lung
      cancer cases and 614 controls aged 40-84, who were residents of their current
      home for at least 20 years, were included. Risk factors examined included
      cigarette smoking, passive smoking, occupation, chemical exposure, previous lung
      disease, family history of cancer, and urban residence. Multiple logistic
      regression analysis was conducted after adjusting for age, education, and
      cumulative radon exposure. RESULTS: As expected, active cigarette smoking was the
      major risk factor for lung cancer. While cessation of smoking was significantly
      associated with a reduced risk for lung cancer, the risk remained significantly
      elevated for 25 years. Among all cases, asbestos exposure was a significant risk.
      Among ex-smokers, pack-year history predominated as the major risk. Among never
      smokers, a family history of kidney or bladder cancer were significant risk
      factors (OR=7.34, 95% CI=1.91-28.18; and OR=5.02, 95% CI=1.64-15.39,
      respectively), as was a history of previous lung disease (OR=2.28, 95% CI=1.24
      4.18) and asbestos exposure. No statistically significant increase in lung cancer
      risk was found for occupation or urban residence. CONCLUSIONS: Smoking prevention
      activities are urgently needed in rural areas of the United States. Relatives of
      individuals with smoking-related cancers are potentially at increased risk.
      Genetic risk factors should be more fully investigated in never smokers.

PMID- 16581202
TI  - Inhalant use and disorders among adults in the United States.
AB  - OBJECTIVE: To examine the patterns of adult inhalant use and correlates of
      inhalant use disorder. METHOD: We drew study data from the 2002 and 2003 National
      Surveys on Drug Use and Health (NSDUH). We used logistic regression to identify
      the characteristics associated both with inhalant use and inhalant use disorder.
      RESULTS: One in 10 of all adults had used an inhalant at least once in their
      lives, and 0.5% used one in the past year. Among all past year inhalant users, 8%
      met the criteria for an inhalant use disorder (i.e., 6.6% for abuse and 1.1% for
      dependence) within that period. We found an increased prevalence of past year
      inhalant use among young adults aged 18-25 years, Asians, past year alcohol
      abusers and dependents, lifetime drug users, white women, and men reporting
      symptoms of serious mental illness. Inhalant-using adults who met the criteria
      for an inhalant use disorder were predominantly adults aged 35-49 years and were
      less educated, had received recent professional treatment for emotional or
      psychological problems, used inhalants weekly, and had a coexisting alcohol use
      disorder. CONCLUSION: The patterns and consequences of adult inhalant use differ
      from those of adolescents. Compared with adolescent inhalant users, adult users
      tend not to initiate inhalant use until adulthood, use inhalants less frequently,
      use fewer inhalants, and are less likely to engage in criminal activities.

PMID- 16581203
TI  - Identification and characterization of a putative ABC transporter PltHIJKN
      required for pyoluteorin production in Pseudomonas sp. M18.
AB  - A putative ABC (ATP-binding cassette) transport gene cluster pltHIJKN was
      identified and characterized within a 7.5-kb genome region downstream of the
      antibiotic pyoluteorin (Plt) biosynthetic gene cluster in Pseudomonas sp. M18, a
      rhizosphere bacterium which is of ecological importance for controlling plant
      diseases caused by soil-borne fungal pathogens. The sequence similarity,
      conserved domains and hydrophobicity profiles strongly suggest that the pltHIJKN
      gene products are integrated into a typical three-component ABC export system,
      which consists of the inner membrane ABC transporter PltIJK, the membrane fusion
      protein PltH and the outer membrane efflux protein PltN. Mutant strains of M18
      defective in pltH or pltI did not produce detectable levels of Plt.
      Overexpression of the entire pltHIJKN gene cluster resulted in a significant
      increase of Plt production. Heterogenous expression of the pltHIJKN gene cluster
      gave rise to a significant enhancement of resistance of E. coli DH5alpha to
      exogenous Plt. These results indicate that PltHIJKN is required for Plt
      biosynthesis and resistance, which is likely to be mediated by Plt export using
      the PltHIJKN transport system. Exogenous Plt induced the expression of both the
      Plt biosynthetic gene cluster and the ABC transport gene cluster pltHIJKN at the
      transcriptional level, suggesting that Plt biosynthesis and expression of
      pltHIJKN are coordinately and similarly regulated in Pseudomonas sp. M18.

PMID- 16581205
TI  - Identification of genomic islands in six plant pathogens.
AB  - Genomic islands (GIs) play important roles in microbial evolution, which are
      acquired by horizontal gene transfer. In this paper, the GIs of six completely
      sequenced plant pathogens are identified using a windowless method based on Z
      curve representation of DNA sequences. Consequently, four, eight, four, one, two
      and four GIs are recognized with the length greater than 20-Kb in plant pathogens
      Agrobacterium tumefaciens str. C58, Rolstonia solanacearum GMI1000, Xanthomonas
      axonopodis pv. citri str. 306 (Xac), Xanthomonas campestris pv. campestris str.
      ATCC33913 (Xcc), Xylella fastidiosa 9a5c and Pseudomonas syringae pv. tomato str.
      DC3000, respectively. Most of these regions share a set of conserved features of
      GIs, including an abrupt change in GC content compared with that of the rest of
      the genome, the existence of integrase genes at the junction, the use of tRNA as
      the integration sites, the presence of genetic mobility genes, the difference of
      codon usage, codon preference and amino acid usage, etc. The identification of
      these GIs will benefit the research for the six important phytopathogens.

PMID- 16581204
TI  - The alleles of PECAM-1.
AB  - Previous studies have reported the existence of eleven different single
      nucleotide polymorphisms (SNPs) within human PECAM-1 mRNA, several of which have
      recently been associated with disease. Though SNPs in the PECAM-1 gene have been
      known for some time, the genetic background on which they exist, and their
      association into distinct allelic isoforms has not yet been established. To
      identify the major allelic isoforms of PECAM-1, we determined the nucleotide
      sequence of individual full-length cloned cDNAs derived from anonymous, unrelated
      volunteer individuals. Initial sequence analysis of 34 alleles from 17
      individuals confirmed the presence of two distinct human PECAM-1 alleles
      (L(98)S(536)R(643) and V(98)N(536)G(643)) within the human population. Each of
      these were found, upon more detailed analysis, to be superimposed on a previously
      unreported a2479g nucleotide polymorphism within the 3' untranslated region
      (3'UTR) that occurred on both allelic isoforms - yielding a total of four major
      alleles. Multiplex Luminex bead analysis of an additional 259 individuals allowed
      identification of 117 individuals homozygous for either the L(98)S(536) or
      V(98)N(536) allele, and sequence analysis around the R643G and a2479g polymorphic
      sites permitted accurate determination of significant differences in the gene
      frequencies of LSRa, LSRg, VNGa, and VNGg among Caucasian individuals.
      Identification of these PECAM-1 allelic isoforms should facilitate future
      detailed examination of PECAM-1-related disease associations, and may help
      resolve previously disparate results.

PMID- 16581207
TI  - The management of renal conditions in the perinatal period.
AB  - Most urogenital abnormalities are now diagnosed antenatally on high resolution
      ultrasound scans. This has enabled recognition of those that are not compatible
      with survival and these are managed with termination of pregnancy. Renal
      anomalies that require surgical intervention continue to pose challenges.
      Conditions such as multicystic dysplastic kidney can be easily recognised and
      managed based on the experience gained with long-term studies of its natural
      history. Polycystic kidney on the other hand while not posing a diagnostic
      problem remains beyond the reach of therapeutic intervention and postnatal
      supportive measures are the only available means of dealing with this entity at
      present. The major difficulty is with the management of antenatally diagnosed
      pelvicalyceal dilatation. The goal of intervention is to preserve renal function
      when dilatation is the consequence of obstruction. Unfortunately, by the time
      ultrasound evidence of significant obstruction is apparent renal damage is
      already established. Fetal intervention should be considered in those cases where
      severe oligohydramnios is associated with hydronephrosis, especially in the
      presence of a solitary kidney or in bilateral disease. Postnatally, all neonates
      with renal tract dilatation should be managed according to a protocol which
      mandates serial measurements of renal pelvis diameter and correlates this with
      data from radionuclide scans. This will enable recognition of kidneys that are at
      risk of losing function while at the same time avoiding unnecessary surgical
      intervention in those which remain dilated but are functionally stable.

PMID- 16581206
TI  - Mimotope of Leptospira from phage-displayed random peptide library is reactive
      with both monoclonal antibodies and patients' sera.
AB  - The study aim was to use random heptapeptide library displayed by bacteriophage
      T7 for identifying mimotopes from 15 monoclonal antibodies (MAbs) specific to
      Leptospira spp., and from four leptospirosis patient sera, respectively. The
      bound phages, selected from fourth round of bio-panning with each antibody, were
      cloned by plaque isolation and the binding specificity of individual clones were
      confirmed by enzyme-linked immunosorbent assay, before being further amplified
      and checked for phage peptide sequence using PCR and DNA sequencing. All together
      150 phages were selected, mimotope from 86 phages (56.6%) were found to match
      with protein sequences of Leptospira from GenBank database. The predominant
      mimotopes were mimotope with sequence LTPCD that found in 27.3%, followed by
      TPCSK (16%), KSKKSS (4%), KTKRXAS (4%), SSKSYR (3.3%), DPNXNSF (3.3%), KSGRC
      (2.6%), TLINIF (2%), TPCI (2%), 1.33% each with mimotopes PKKS, PCNTKXTA, and
      CTKKK, and one phage each (0.66%) with mimotopes PTFGS, TNSKRK, SKSSRC, RSKRIR,
      VTNNTP, and CSNXSKR. Interestingly, mimotopes LTPCD, TPCSK, and TPCI were found
      to react with both MAb and patient's sera. The matched proteins from GenBank
      namely, leptospiral putative outer membrane protein (matched with mimotope
      PTFGS), thermolysin precursor protein (matched with mimotope TPCIXXGSAS), and
      hypothetical protein LIC12228 (matched with mimotope CSNXSKR), were found to
      locate at outer membrane of Leptospira. These phage mimotopes and matched
      proteins may have potential for further use as diagnostic reagent and immunogen
      against leptospirosis in the future. The results demonstrate that phage display
      technique has potential for rapidly identifying phage mimotopes that interact
      with leptospiral MAbs and patient's sera.

PMID- 16581208
TI  - Management of congenital lung lesions.
AB  - Antenatally diagnosed lung lesions are most commonly congenital cystic
      adenomatiod malformations (CCAMs) or bronchopulmonary sequestrations (BPS).
      Congenital lobar emphysema and bronchogenic cysts occur rarely. CCAMs and BPS can
      only be truly distinguished on histopathological assessment. CCAMs can be defined
      using either Stocker's histological classification, or the clinically more useful
      'macrocystic' and 'microcystic' subtypes introduced by Adzick. Adverse
      pathophysiological effects (e.g. lung hypoplasia, mediastinal shift, caval
      obstruction and hydrops) can occur with those of larger volume in the developing
      fetus and are associated with a poor outcome ( approximately 5%). In centres with
      appropriate expertise, antenatal intervention (e.g. thoracoamniotic shunting)
      should be considered for such cases. In the postnatal period, early radiological
      evaluation (e.g. CT scan) is essential as many cases which apparently 'regress'
      antenatally are still detectable and may be a cause of later morbidity. Early
      surgical excision is required for symptomatic cases and should also be considered
      for asymptomatic antenatally diagnosed lesions, because of the risks of later
      infection and the possibility of malignant transformation. An excellent outcome
      following surgery can be expected.

PMID- 16581210
TI  - The risk factors and symptomatology of perimenopausal depression.
AB  - OBJECTIVES: The aim of this study is to determine if the depression in
      perimenopausal women is symptomatologically different than depression in
      premenopausal women, and if these depressive women are under more risk for
      depression when factors like premenstrual dysphoric syndrome, socio-economical
      status, vasomotor symptoms and familial inclination to depression are considered.
      METHODS: Fifty major depressive women with hormonally established perimenopause
      (follicle stimulating hormone (FSH) levels over 20IU/l and estrogen levels lower
      than 40IU/l) and who were not taking any psychotropic or hormone replacement
      therapy, were enrolled in the study. In order to investigate the characteristic
      clinical features of perimenopausal depression, a drug free control group
      consisting of 48 pre-perimenopausal women with a diagnosis of major depression
      was formed. Another control group was formed with 53 non-depressive
      perimenopausal women in order to investigate the risk factors of perimenopausal
      depression. RESULTS: The depressive and non-depressive groups did not differ from
      each other according to level of education, marital and economical status and
      comorbid physical problems. No major symptomatological difference between
      perimenopausal depression and pre-perimenopausal depression was found. No
      correlation was found between the severity of vasomotor symptoms and severity of
      depression. CONCLUSIONS: Findings of our study suggest that vasomotor symptoms
      and socio-economical status do not predict the severity and existence of
      perimenopausal depression. Episodes of major depression are not necessarily the
      normal result of such vasomotor symptoms. Therefore, the evaluation and
      management of perimenopausal depression should be carried out as carefully as is
      done in episodes of depression seen in the rest of women's life span.

PMID- 16581209
TI  - Tibolone and its metabolites inhibit invasion of human mammary carcinoma cells in
      vitro.
AB  - Tibolone is used in postmenopausal women to alleviate menopausal symptoms and to
      prevent osteoporosis, but it does not stimulate the endometrium and the breast.
      Up to date, little data are available on the effect of tibolone on breast cancer
      initiation and progression. OBJECTIVE: In the present in vitro study, we
      investigated the effect of tibolone and its metabolites (3alpha-OH tibolone,
      3beta-OH tibolone, the Delta4 isomer and the sulphated isoform) on invasion of
      human breast cancer cells. METHODS: The effect on invasion was evaluated in the
      chick heart invasion assay using MCF-7/6 cells and in the collagen type I
      invasion assay using T47-D cells. Furthermore, the compounds were tested in
      aggregation and migration assays. RESULTS: We observed that, at a concentration
      of 100 microM, tibolone and its 3beta-OH metabolite possess anti-invasive
      activities in the two different invasion assays. However, this was neither due to
      effects on cell-cell adhesion nor on motility. In an attempt to probe the
      mechanism underlying the anti-invasive effect, we found that pro-MMP-9 release
      was markedly reduced in the supernatant of MCF-7/6 breast cancer cells treated
      with tibolone, 3alpha-OH tibolone and the Delta4 isomer but, interestingly, not
      with the sulphated metabolite. CONCLUSION: We conclude that tibolone and its
      3beta-OH metabolite have an anti-invasive effect on the tested breast cancer cell
      lines in vitro. This effect on invasion is not correlated with an effect on cell
      cell adhesion or motility but coincides with a decreased release of pro-MMP-9 in
      the medium.

PMID- 16581212
TI  - Evidence on unusual way of cocaine smuggling: cocaine-polymethyl methacrylate
      (PMMA) solid solution--study of clandestine laboratory samples.
AB  - An abandoned clandestine laboratory was seized in Slovenia. All confiscated
      exhibits were analysed in a forensic laboratory, where the following analytical
      methods were applied: capillary gas chromatography coupled with mass spectrometry
      (GC-MS) combined also by solid-phase micro extraction (SPME) and pyrolysis (Py)
      technique, Fourier transform infrared spectrometry (FTIR) and scanning electron
      microscopy with energy dispersive X-ray detector (SEM-EDX). The most interesting
      analytical findings can be summarised as follows: at the crime scene some plastic
      pieces, which contained cocaine dissolved (as solid solution) in polymethyl
      methacrylate-plexiglass (PMMA), were found. The highest cocaine concentration
      measured in the plastic sample was about 15% by weight. Two larger lumps of
      material (12 and 3 kg) were composed mainly of PMMA and CaCO3 and contained only
      0.4 and 0.5% of cocaine, respectively. As for the low cocaine concentration, we
      assume that those two lumps of material represent discarded waste product-
      residue after the isolation of cocaine from plastic. Higher quantities of pure
      solvents (41 l) and solvent mixtures (87 l) were seized. We identified three
      types of pure solvents (acetone, gasoline and benzine) and two different types of
      solvent mixtures (benzine/acetone and gasoline/acetone). The total seized volume
      (87 l) of solvent mixtures holds approximately 395 g of solid residue formed
      mainly of PMMA and cocaine. Obviously solvent mixtures were used for isolation of
      cocaine from the plastic. Small quantities of relatively pure cocaine base were
      identified on different objects. There were two cotton sheets, most probably used
      for filtration. One sheet had traces of cocaine base (76% purity) on the surface,
      while cocaine in hydrochloride form (96%) was identified on the other sheet. GC
      MS analyses of micro traces isolated from analytical balances showed the presence
      of cocaine and some common adulterants: phenacetine, lidocaine and procaine. A
      cocaine sample compressed in the shape of block was also seized. The above
      analytical findings inferred us to the conclusion that the illicit laboratory was
      used for the isolation of cocaine from PMMA resin. Further more, analyses confirm
      that not only isolation but also further manipulation of cocaine, i.e.
      adulteration/dilution, as well as the formation of cocaine blocks took place in
      the house. The information obtained through analyses also allowed us to make some
      hypotheses about possible multistage isolation procedure.

PMID- 16581211
TI  - Influence of modified cyclodextrins on solubility and percutaneous absorption of
      celecoxib through human skin.
AB  - We evaluated the ability of two modified cyclodextrins, hydroxypropyl-beta
      cyclodextrin (HP-beta-Cyd) and 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-Cyd),
      to influence the percutaneous absorption through isolated human stratum corneum
      and epidermis (SCE) of celecoxib (CCB). Previous studies demonstrated that DM
      beta-Cyd includes the drug, producing a significant increase of water solubility
      (0.5 mg/ml at 25 degrees C) and dissolution rate of CCB. In this work chemical
      physical characterization studies were performed to evaluate the ability of HP
      beta-Cyd to include CCB. We showed that only an external interaction could exist
      between CCB and HP-beta-Cyd that positively influences the water solubility of
      the drug (0.12 mg/ml at 25 degrees C for CCB-HP-beta-CyD system and 4.12 x 10(-3)
      mg/ml at 25 degrees C for free CCB). In vitro percutaneous experiments were
      performed using samples in solution and in suspension containing different Cyd
      concentrations. Both HP-beta-Cyd and DM-beta-Cyd enhanced drug flux through SCE
      by means of an increase of dissolution rate of the drug as well as a direct
      action on the stratum corneum (SC). Histological analysis of treated SCE showed a
      protective effect of the two Cyds towards an invasive action shown by CCB on SC.

PMID- 16581213
TI  - [Impact study of an active antiflu vaccination programme on the Clermont-Ferrand
      Teaching Hospital staff].
AB  - OBJECTIVE: Protecting health care units from influenza epidemics has a double
      purpose: to decrease the mortality rate of patients at risk and to reduce work
      leave in medical staff. An annual vaccination appears to be the most effective
      prevention against influenza. In France however the vaccinal coverage of health
      workers does not exceed 15%. METHOD: In the 2003-2004 winter, the department of
      occupational health and the nosocomial disease committee of the Clermont-Ferrand
      Teaching Hospital initiated an active vaccination campaign. Three joint actions
      were carried out: date and place of vaccination sessions were individually
      addressed to every healthcare worker, meetings on prevention of influenza were
      held, as well as vaccination sessions on the work place in exposed units.
      RESULTS: Significant results were noted: vaccination rate increased 2.6 fold
      compared to the previous year (4.8 to 12.6%) and a vaccinal coverage rate of 29%
      in the exposed units. COMMENTS: The results even if far from national objectives
      encourage the pursuit of the campaigns promoting information and vaccination on
      the work place. The high frequency of reported postinjection adverse effects (1
      out of 3) should be taken into account in future information campaign.

PMID- 16581214
TI  - [Cases of pertussis among healthcare workers in a maternity ward: management of a
      health alert].
AB  - Pertussis is a highly contagious acute respiratory tract infection, with a poor
      prognosis in non-vaccinated new-borns. OBJECTIVES: The authors had for aim to
      investigate an epidemic of 5 pertussis cases among health care workers (HCW) in
      our maternity ward with potential exposure of new-borns and to evaluate HCW
      compliance and experience gain. METHODS: A retrospective study was made using a
      questionnaire with HCW on preventive measures taken (antibiotic prophylaxis with
      erythromycin and wearing a mask). RESULTS: Two hundred and thirty-eight patients
      were warned of a potential pertussis contamination. No nosocomial case was
      detected among patients or their new borns. Ten proved or probable cases were
      identified among 101 HCW having answered (N=101/210, 48%). Sixty percent of HCW
      people followed the antibiotic treatment and 85% wore a mask among whom 46%
      adequately. Non-compliance factors were mainly related to adverse effects (41%),
      delayed information (41%), and false vaccine protection (22%). Crisis
      communication was felt as unsatisfactory for 72% of HCW and recommendations not
      adapted for 39% of the staff. CONCLUSION: This survey points out the difficulty
      of managing a pertussis alert in a medical ward.

PMID- 16581215
TI  - [Factors for non-observance of the extended program timetable for vaccination in
      health districts: the case of Bousse in Burkina Faso].
AB  - Prevention through vaccination is a strong means to fight pediatric lethal
      diseases. In Burkina Faso, one of the main problems for vaccination is the non
      respect of the vaccination timetable bringing about a significant reduction of
      validity of administered doses. OBJECTIVES: The authors had for aim to assess
      reasons for the non-compliance to the timetable. A transversal study was carried
      out in the Bousse health district to: 1) analyze the qualitative and
      organizational factors of the vaccination services linked to this non compliance;
      2) analyze community factors accounting for this situation. POPULATION AND
      METHOD: The study target group included mothers of children aged 0 to 11 months
      vaccinated by the vaccination team of the Bousse health district from August 1st,
      2003 to June 30th, 2004, and the vaccination team. Variables covered in this
      study included sociodemographic factors, the organization of vaccination
      campaigns, the mothers' perception of health service organization, the
      vaccination team's experience, vaccinal safety, knowledge of vaccination
      timetable. RESULTS: The following were identified as key factors for the non
      observance of the vaccination timetable: poor organization of the vaccination
      services, inadequate competence of the vaccination team, poor educational level
      of mothers, poor communication level with mothers, postvaccination side effects.
      CONCLUSION: The study recommends the following: training of vaccination
      providers, a better organization of vaccination services, and the implementation
      of a communication plan.

PMID- 16581216
TI  - Antioxidant enzymes activities and protein damage in rat brain of both sexes.
AB  - The theory of free radicals and accumulation of damages suggests that the
      reactive species of oxygen play a key role in the context of aging. Thus, for the
      best understanding of the aging process, the study of antioxidant defenses has to
      be considered as part of gerontology. The present work evaluated the enzymatic
      activity of the enzymes catalase (CAT), glutathione peroxidase (GPx) and
      superoxide dismutase (SOD), and measured the amount of oxidative damage in
      proteins (carbonyl groups) in brains of rats of both sexes in the ages of 3-, 6-,
      12- and 20-months. The results suggest that the patterns of activity and
      accumulation of damages can be sex-specific and related to the cycle of
      reproductive life of the organism.

PMID- 16581217
TI  - Two components in pathogenic mechanism of mitochondrial ATPase deficiency: energy
      deprivation and ROS production.
AB  - Isolated defects of mitochondrial ATPase due to diminished biosynthesis of the
      enzyme represent new class of severe mitochondrial diseases of nuclear origin.
      The primary cause of decreased cellular content of ATPase appears to be a problem
      in assembly of the F1 catalytic part of the enzyme. With the aim to elucidate how
      the low ATPase content affects mitochondrial energy provision and ROS production,
      we have investigated fibroblasts from patients with ATPase decrease to 10-30%.
      Measurements of cellular respiration showed pronounced decrease in ATPase
      capacity for basal respiration, mitochondrial ATP synthesis was decreased to 26
      33%. Cytofluorometric analysis using TMRM revealed altered discharge of
      mitochondrial membrane potential (DeltaPsim) in patient cells, which was 20 mV
      increased at state 3-ADP. Analysis of ROS production by CM-H2DCFDA demonstrated 2
      fold increase in ROS production in patient cells compared to controls. ROS
      production rate was sensitive to uncoupler (FCCP) and thus apparently related to
      increased DeltaPsim. Our studies clearly demonstrate that low ATPase content and
      decreased mitochondrial ATP production lead to high values of DeltaPsim and are
      associated with activation of ROS generation by the mitochondrial respiratory
      chain. In conclusion, both the energetic deprivation and increased oxidative
      stress are important components of the pathogenic mechanism of ATPase disorders.

PMID- 16581218
TI  - Determination of steroid sex hormones in water and urine matrices by stir bar
      sorptive extraction and liquid chromatography with diode array detection.
AB  - In this study, stir bar sorptive extraction and liquid desorption followed by
      high performance liquid chromatography with diode array detection (SBSE-LD
      HPLC/DAD) were combined for the simultaneous determination of nine steroid sex
      hormones (estrone, 17alpha-estradiol, 17beta-estradiol, 17alpha-ethynylestradiol,
      diethylstilbestrol, mestranol, progesterone, 19-norethisterone and norgestrel) in
      water and urine matrices. During the method development, it has been demonstrated
      that equilibrium time, ionic strength and back extraction solvents are the most
      important parameters to control, for determining the nine-hormones in water
      matrices, in which stir bars coated with 126 microl of polydimethylsiloxane were
      used. Assays performed on 30 ml water samples spiked at 10 microg/l levels under
      optimised experimental conditions, yielded recoveries ranging from 11.1+/-4.9%
      (17beta-estradiol) to 100.2+/-10.4% (mestranol), showed that the methodology is
      well described by the octanol-water partition coefficients (K(PDMS/W)
      approximately K(O/W)) for the latter, while pronounced deviations to the
      theoretical efficiency (K(PDMS/W) not equal K(O/W)) were observed for the
      remaining hormones. From calibration studies, a good analytical performance for
      all hormones was attained, including a suitable precision (2.1-17.1%), low limits
      of detection (0.3-1.0 microg/l) and an excellent linear dynamic range (1.25-50.0
      microg/l). Assays on environmental water and urine matrices showed recovery
      yields in worthy good agreement with the spiking level (10 microg/l), and
      suitability for profiling low microg/l levels of natural hormones in urine
      samples taken from pregnant women. The present methodology is easy, reliable and
      sensitive at the trace level, only requiring a low sample volume, showing to be a
      good analytical alternative to routine quality control for environmental and
      biomedical laboratories.

PMID- 16581219
TI  - Profiling urinary metabolites of naproxen by liquid chromatography-electrospray
      mass spectrometry.
AB  - Glucuronidation, an important metabolic process for the biotransformation of
      drugs into easily eliminable water-soluble detoxification products, can also lead
      to biologically active or toxic glucuronide conjugates. The present work
      describes a liquid chromatography-electrospray mass spectrometry (LC-ESI-MS)
      approach for the characterization of naproxen and O-6-desmethylnaproxen
      glucuronides. The method is fast and efficient and permitted to individuate alpha
      and beta isomers of both naproxen and O-6-desmethylnaproxen glucuronides. The
      procedure could be potentially extended to the characterization of other drug
      metabolites.

PMID- 16581220
TI  - [Horner's syndrome following internal jugular vein cannulation].

PMID- 16581221
TI  - [Butyrylcholinesterase deficiency: how to analyse the cholinesterase activity in
      small children?].
AB  - We report the case of a prolonged neuromuscular blockade in an 18-month-old age
      girl following administration of a usual dose of succinylcholine. The diagnosis
      was highly suggested by the clinical history while cholinesterase activity was
      included in adult normal values but below values of a personal series of 41 small
      children. The familial analysis of dibucaine and fluoride number confirmed the
      hypothesis of an atypical variant (AA phenotype). The cholinesterase activity is
      higher in small children than in adult and has to be analysed according to the
      age.

PMID- 16581222
TI  - The effect of nitric oxide on the production of prostaglandin E2 by
      hydroxyapatite-stimulated a human osteoblast (HOS) cell line.
AB  - The aim of the present study was to determine the effect of nitric oxide (NO) on
      the production of prostaglandin E2 (PGE2) by a human osteoblast cell line (HOS
      cells) stimulated with hydroxyapatite. Cells were cultured on the HA surfaces
      with or without the presence of NO donors (SNAP and NAP) for 3 days. The effect
      of NO scavenger, carboxy PTIO, or endothelial nitric oxide synthase (eNOS)
      inhibitor, L-NIO, was assessed by adding this scavenger in the cultures of HA
      stimulated HOS cells with or without the presence of SNAP. Furthermore, HOS cells
      were pre-treated with anti-human integrin alphaV antibody, indomethacin, a non
      specific inhibitor, aspirin, a COX-1 inhibitor, or nimesulide, a COX-2 inhibitor,
      prior to culturing on HA surfaces with or without the presence of SNAP. The
      levels of PGE2 were determined from the 3 day culture supernatants. The results
      showed that the production of PGE2 by HA-stimulated HOS cells was augmented by
      SNAP. Carboxy PTIO suppressed but L-NIO only partially inhibited the production
      of PGE2 by HA-stimulated HOS cells with or without the presence of exogenous NO.
      Pre-treatment of the cells with anti-human integrin alphaV antibody, indomethacin
      or nimesulide but not aspirin suppressed the production of PGE2 by HA-stimulated
      HOS cells with or without the presence of NO. Therefore, the results of the
      present study suggest that NO may up-regulate the production of PGE2 by
      augmenting the COX-2 pathway initiated by the binding between HOS cell-derived
      integrin alphaV and HA surface.

PMID- 16581223
TI  - Matrix metalloproteinases and their inhibitors as biomarkers for metal toxicity
      in vitro.
AB  - Exposure to nickel and chromium, and their compounds, has been associated with
      adverse health effects. These metals are two human carcinogens whose pathogenesis
      involves active extracellular matrix degradation and remodelling. In this work we
      have compared the effects of in vitro exposure to nickel and chromium of a
      keratinocyte cell line (HaCat). The modulation of matrix metalloproteinase genes
      was used as biomarker of chemical damage. Confluent cells were constantly exposed
      to subtoxic chromium and nickel concentrations (10(-5) and 10(-7)M) up to 72 h.
      Total RNA was extracted and specific matrix metalloproteinase, and inhibitor,
      gene expression was analyzed by RT-PCR. Moreover, cell cycle alterations were
      evaluated by flow cytometry. Nickel and chromium showed different results, with
      an upregulation of MMP-2 mRNA production in nickel-treated cells while chromium
      exposure down-regulated MMP-2 mRNA production. This result could be correlated to
      the precocious (6h) over-expression of tissue inhibitor-1 (TIMP-1) mRNA in
      chromium-treated cells. Cell cycle analysis showed and increase of cells with 4N
      DNA. These results could be explained as a survival response of cells that escape
      metal induced apoptosis through the anti-apoptotic effects of TIMP-1. These cells
      that encompass the genotoxic insult may have a selective proliferation advantage,
      and therefore represent the precursor pool from which degenerating variants may
      emerge. To study if the chemical damage was reversible, subconfluent cells were
      stimulated only for 24 h, then the medium was replaced without metal. Cells were
      able to recover from nickel exposure, showing only weak alterations in specific
      mRNA expression and cell cycle alteration respect to control. Chromium-induced
      damage was irreversible. Our results demonstrated that there is an association
      between metal toxicity and expression of MMPs and their inhibitors. These
      biomarkers could be potentially useful to elaborate a prediction model of
      chemical toxicity.

PMID- 16581224
TI  - Sodium nitrite-induced cytotoxicity in cultured human gastric epithelial cells.
AB  - To investigate the effect of sodium nitrite on the viability of the human gastric
      adenocarcinoma epithelial cell line, AGS, cultured AGS cells were exposed to
      various concentrations of sodium nitrite for 24, 48 or 72 h. The cytotoxic
      response was assessed using a cell proliferation assay, and the extent of the
      response was evaluated on the basis of intracellular and extracellular levels of
      interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 8 (IL-8) and
      tumor necrosis factor (TNF-alpha). Both mRNA and protein levels were measured for
      each cytokine. Sodium nitrite had a significant effect on AGS cell proliferation
      after a 72-h exposure. At low sodium nitrite concentrations (up to 6.25 mM), cell
      proliferation increased in a dose-dependent manner; however, exposure to higher
      concentrations resulted in a dose-dependent decrease in cell proliferation.
      Sodium nitrite at a low concentration (6.25 mM) increased IL-8 release, whereas
      IL-1 beta, IL-6, and TNF-alpha release increased only after exposure to high
      sodium nitrite concentration (25 mM). Our data demonstrate that sodium nitrite
      can induce the release of these inflammatory cytokines and that high
      concentrations of sodium nitrite decrease AGS cell proliferation.

PMID- 16581225
TI  - Response to alkyltins of two Na+-dependent ATPase activities in Tapes
      philippinarum and Mytilus galloprovincialis.
AB  - Organotin effects on the Na-dependent ATPases involved in ionic regulation of
      aquatic animals are poorly known, in spite of the largely documented
      contamination of seafood, especially bivalve molluscs. This study deals with the
      in vitro effect of TBT on the Na,K-ATPase and the ouabain-insensitive Na-ATPase
      in gill and mantle microsomes from the cultured bivalve molluscs Tapes
      philippinarum and Mytilus galloprovincialis. In the mussel also MBT, DBT and TeET
      were tested. While in both species the Na-ATPase showed an overall refractoriness
      to organotins, the Na,K-ATPase was progressively inhibited by increasing TBT
      concentrations (0-34 microM). In both species the Na,K-ATPase activity was more
      strongly inhibited in the gills than in the mantle. At the maximal TBT
      concentration tested (34.4 microM), while gill Na,K-ATPase activity was
      abolished, mantle enzyme activity was, respectively, reduced to 20% in T.
      philippinarum and to 50% in M. galloprovincialis. Mussel Na,K-ATPase was
      differently susceptive to the organotins tested and in both tissues showed an
      inhibition efficiency order TBT>DBT>>MBT=TeET (no effect), tentatively related to
      the different organotin polarity and to a possible interaction with membrane
      bound enzyme complexes. The different response of the two ATPases to organotins
      is consistent with the known different susceptivity of the two enzyme activities
      to environmental contaminants, assay conditions and endogenous factors.

PMID- 16581226
TI  - Atypical behaviors in children with autism and children with a history of
      language impairment.
AB  - The frequency, course, and inter-relationships of atypical eating, sleeping, self
      injurious behavior, aggression and temper tantrums in children with autism and
      children with a history of language impairment (HLI), was investigated using a
      parent interview that was created to examine these problem behaviors. The
      relationships between these behaviors and language, IQ, severity of autistic
      symptoms and depression were also assessed. Atypical eating behavior, abnormal
      sleep patterns, temper tantrums, and self-injurious behavior were significantly
      more common in the children with autism than those with HLI. Within the autism
      group, children who exhibited more atypical behaviors tended to have a lower
      nonverbal IQ, lower levels of expressive language, more severe social deficits
      and more repetitive behaviors. No relationship between the number of atypical
      behaviors and measures of cognitive or language ability was noted in the HLI
      group. However, having more atypical behaviors was related to increased
      restricted, repetitive behaviors in children with HLI. The atypical behaviors
      could be divided into two groups: abnormal eating and sleeping, which were
      independent and tended to begin early in life; and self-injury, tantrums and
      aggression, which began later and were inter-related. Sleep abnormalities were
      more common in children (groups combined) diagnosed with major depression.

PMID- 16581227
TI  - Outcome of resonant voice therapy for female teachers with voice disorders:
      perceptual, physiological, acoustic, aerodynamic, and functional measurements.
AB  - Teachers have a high percentage of voice problems. For voice disordered teachers,
      resonant voice therapy is hypothesized to reduce voice problems. No research has
      been done on the physiological, acoustic, and aerodynamic effects of resonant
      voice therapy for school teachers. The purpose of this study is to investigate
      resonant voice therapy outcome from perceptual, physiological, acoustic,
      aerodynamic, and functional aspects for female teachers with voice disorders. A
      prospective study was designed for this research. The research subjects were 24
      female teachers in Taipei. All subjects received resonant voice therapy in groups
      of 4 subjects, 90 minutes per session, and 1 session per week for 8 weeks. The
      outcome of resonant voice therapy was assessed from auditory perceptual judgment,
      videostroboscopic examination, acoustic measurements, aerodynamic measurements,
      and functional measurements before and after therapy. After therapy the severity
      of roughness, strain, monotone, resonance, hard attack, and glottal fry in
      auditory perceptual judgments, the severity of vocal fold pathology, mucosal
      wave, amplitude, and vocal fold closure in videostroboscopic examinations,
      phonation threshold pressure, and the score of physical scale in the Voice
      Handicap Index were significantly reduced. The speaking Fo, maximum range of
      speaking Fo, and maximum range of speaking intensity were significantly increased
      after therapy. No significant change was found in perturbation and breathiness
      measurements after therapy. Resonant voice therapy is effective for school
      teachers and is suggested as one of the therapy approaches in clinics for this
      population.

PMID- 16581228
TI  - Vocal tract area function for vowels using three-dimensional magnetic resonance
      imaging. A preliminary study.
AB  - OBJECTIVE: To assess whether magnetic resonance imaging (MRI) allows the vocal
      tract (VT) area function to be determined for a normal male speaker. METHOD: VT
      shapes were acquired using MRI during sustained production of French points
      vowels: /i/, /a/, /u/. Cross-sectional areas were measured from a series of
      planes spaced at intervals of 1 cm along the length of the VT and were used as
      input in a previously described VT model to simulate the vowels. The first three
      formant frequencies, F1, F2, and F3, computed from the MRI-measured VT model were
      compared with subject's natural formant frequencies. RESULTS: Including piriform
      sinuses, calculated formants differed from measured formants F1, F2, and F3,
      respectively, for /i/ by -3.5%, +7.7%, and +27.5%; for /a/ by +11% +19.5%, and 
      4.3%; and for /u/ by +.9%, +23.4%, and +9.6%. Excluding piriform sinuses,
      calculated formants differed from measured formants F1, F2, and F3, respectively,
      for /i/ by -3.5%, +12%, and +28%, and for /u/ by +10.1%, +26.8%, and +13.7% The
      piriform sinuses were not visualized for /a/ on MRI. CONCLUSIONS: MRI is a
      noninvasive technique that allows VT imaging and determination of VT area
      function for a normal male speaker. Several possible sources of discrepancies are
      as follows: variability of the articulation, difficulties in assessment of VT
      wall boundaries, role of the piriform sinuses, and VT length.

PMID- 16581229
TI  - Treatment outcomes for professional voice users.
AB  - Professional voice users comprise 25% to 35% of the U.S. working population.
      Their voice problems may interfere with job performance and impact costs for both
      employers and employees. The purpose of this study was to examine treatment
      outcomes of two specific rehabilitation programs for a group of professional
      voice users. Eighteen professional voice users participated in this study; half
      had complaints of throat pain or vocal fatigue (Dysphonia Group), and half were
      found to have benign vocal fold lesions (Lesion Group). One group received 5
      weeks of expiratory muscle strength training followed by six sessions of
      traditional voice therapy. Treatment order was reversed for the second group. The
      study was designed as a repeated measures study with independent variables of
      treatment order, laryngeal diagnosis (lesion vs non-lesion), gender, and time.
      Dependent variables included maximum expiratory pressure (MEP), Voice Handicap
      Index (VHI) score, Vocal Rating Scale (VRS) score, Voice Effort Scale score,
      phonetogram measures, subglottal pressures, and acoustic and perceptual measures.
      Results showed significant improvements in MEP, VHI scores, and VRS scores,
      subglottal pressure for loud intensity, phonetogram area, and dynamic range. No
      significant difference was found between laryngeal diagnosis groups. A
      significant difference was not observed for treatment order. It was concluded
      that the combined treatment was responsible for the improvements observed. The
      results indicate that a combined modality treatment may be successful in the
      remediation of vocal problems for professional voice users.

PMID- 16581230
TI  - Regulation of stretch-induced JNK activation by stress fiber orientation.
AB  - Cyclic mechanical stretch associated with pulsatile blood pressure can modulate
      cytoskeletal remodeling and intracellular signaling in vascular endothelial
      cells. The aim of this study was to evaluate the role of stretch-induced actin
      stress fiber orientation in intracellular signaling involving the activation of c
      jun N-terminal kinase (JNK) in bovine aortic endothelial cells. A stretch device
      was designed with the capability of applying cyclic uniaxial and equibiaxial
      stretches to cultured endothelial cells, as well as changing the direction of
      cyclic uniaxial stretch. In response to 10% cyclic equibiaxial stretch, which did
      not result in stress fiber orientation, JNK activation was elevated for up to 6
      h. In response to 10% cyclic uniaxial stretch, JNK activity was only transiently
      elevated, followed by a return to basal level as the actin stress fibers became
      oriented perpendicular to the direction of stretch. After the stress fibers had
      aligned perpendicularly and the JNK activity had subsided, a 90-degree change in
      the direction of cyclic uniaxial stretch reactivated JNK, and this activation
      again subsided as stress fibers became re-oriented perpendicular to the new
      direction of stretch. Disrupting actin filaments with cytochalasin D blocked the
      stress fiber orientation in response to cyclic uniaxial stretch and it also
      caused the uniaxial stretch-induced JNK activation to become sustained. These
      results suggest that stress fiber orientation perpendicular to the direction of
      stretch provides a mechanism for both structural and biochemical adaptation to
      cyclic mechanical stretch.

PMID- 16581231
TI  - Insulin receptor deficits in schizophrenia and in cellular and animal models of
      insulin receptor dysfunction.
AB  - Schizophrenia is associated with abnormalities in glucose metabolism that may
      lead to insulin resistance and a 3 fold higher incidence of type II diabetes
      mellitus. The goal of the present studies was to assess the role of insulin
      dependent Akt signaling in schizophrenia and in animal and cellular models of
      insulin resistance. Our studies revealed a functional decrease in insulin
      receptor (IR)-mediated signal transduction in the dorsolateral prefrontal cortex
      (BA46) of medicated schizophrenics relative to control patients using post-mortem
      brain material. We found approximately 50% decreases in the content and
      autophosphorylation levels of IRbeta and approximately 76-78% decreases in Akt
      content and activity (pSer(473)-Akt). The inhibition of IRbeta signaling was
      accompanied by an elevated content of glycogen synthase kinase (GSK)-3 alpha and
      GSK-3beta without significant changes in phospho-Ser(21/9) GSK-3 alpha/beta
      levels. A cellular model of insulin resistance was induced by IRbeta knockdown
      (siRNA). As in schizophrenia, the IRbeta knockdown cells demonstrated a reduction
      in the Akt content and activity. Total GSK-3 alpha/beta content remained
      unaltered, but phospho-Ser(21/9) GSK-3 alpha/beta levels were reduced indicating
      a net increase in the overall enzyme activity similar to that in schizophrenia.
      Insulin resistance phenotype was induced in mice by treatment with antipsychotic
      drug, clozapine. Behavioral testing showed decreases in startle response
      magnitude in animals treated with clozapine for 68 days. The treatment resulted
      in a functional inhibition of IRbeta but the Akt activation status remained
      unaltered. Changes in GSK-3 alpha/beta were consistent with a net decrease in the
      enzyme activity, as opposed to that in schizophrenia. The results suggest that
      alterations in insulin-dependent Akt signaling in schizophrenia are similar to
      those observed in our cellular but not animal models of insulin resistance. In
      animal model, clozapine ameliorates IRbeta deficits at the GSK-3 alpha/beta
      level, which may justify its role in treatment of schizophrenia. Our studies
      suggest that aberrant IR function may be important in the pathophysiology of
      schizophrenia.

PMID- 16581232
TI  - Effects of neurosteroids on glucocorticoid receptor-mediated gene transcription
      in LMCAT cells--a possible interaction with psychotropic drugs.
AB  - Aberrant activity of hypothalamic-pituitary-adrenal (HPA) axis is often observed
      in psychiatric disorders and both antidepressant and antipsychotic drugs are
      known to ameliorate some deleterious effects of glucocorticoids on brain
      function. Some neurosteroids possess antidepressant and neuroleptic-like
      properties and attenuate the stress-activated HPA axis activity. However,
      intracellular mechanism of neurosteroid interaction with glucocorticoids has not
      been elucidated. We evaluated effects of some neurosteroids on functional
      activity of glucocorticoid receptor (GR) in vitro. A combined treatment with
      antipsychotic drugs and involvement of some protein kinases in allopregnanolone
      effect on GR function were also studied. The effects of allopregnanolone, its two
      isomers (5beta-pregnan-3alpha-ol-20-one and 5alpha-pregnan-3beta-ol-20-one) and
      dehydroepiandrosterone sulfate (DHEAS) on the corticosterone-induced
      chloramphenicol acetyl transferase (CAT) activity were evaluated in mouse
      fibroblast cells stably transfected with mouse mammary tumor virus (MMTV)-CAT
      plasmid. We found that allopregnanolone (1-100 microM) and, to a lesser extent,
      both its isomers inhibited the GR-mediated gene transcription in a concentration
      dependent manner. In contrast, DHEAS at the concentration up to 100 microM was
      inactive. Further experiments revealed that allopregnanolone and antipsychotic
      drugs (chlorpromazine and clozapine) showed a moderate, additive inhibitory
      effect on the GR function. With respect to intracellular mechanism of
      allopregnanolone action, we showed that this neurosteroid inhibited protein
      kinase C (PKC) activity, decreased the level of PKCalpha isoenzyme in the
      membrane fraction and decreased the amount of active phosphorylated form of
      extracellular signal-regulated kinase-mitogen-activated protein kinase (ERK-MAPK)
      in LMCAT cells. Since PKC and ERK-MAPK inhibitors attenuate the corticosterone
      mediated gene transcription, the above findings suggest that allopregnanolone
      effect on GR function involves interaction with these kinase pathways. On the
      other hand, allopregnanolone had no effect on protein kinase A (PKA) activity.
      These data indicate that pregnanolone derivatives, like antidepressants and
      antipsychotic drugs, may attenuate some glucocorticoid effects via inhibition of
      GR-mediated gene transcription. Furthermore, the inhibitory effect of
      allopregnanolone on the corticosterone-induced gene transcription in LMCAT cells
      depended on the inhibition of PKC and ERK-MAPK pathways.

PMID- 16581233
TI  - Microcalorimetric studies on the adsorption of DNA by soil colloidal particles.
AB  - This study applied TAM air isothermal calorimeter to measure the adsorption
      enthalpies of DNA on eight colloidal fractions from permanent-charge and variable
      charge soils. The adsorption of DNA on soil colloids was also examined by
      equilibrium adsorption analysis. The data evaluated from isotherms fitted by
      Langmuirean model revealed that the affinity of DNA for variable-charge soil
      colloids was higher than that for permanent-charge soil colloids. More tightly
      bound DNA molecules were observed on coarse clays and inorganic clays than on
      fine clays and organic clays, respectively. The adsorption enthalpies of DNA on
      permanent-charge soil colloids were higher than those on variable-charge soil
      colloids. DNA adsorption on organic clays is endothermic, whereas that on
      inorganic clays is exothermic. Dehydration and electrostatic repulsion were
      considered to cause the higher adsorption enthalpies of DNA with organic clays,
      while hydrogen bonding, ligand exchange and electrostatic attraction result in
      the lower DNA adsorption enthalpies on inorganic clays. The thermodynamic
      parameters presented in this study have important implication for providing
      further insight into mechanisms of the adsorption of DNA on soil particles.

PMID- 16581234
TI  - Characterisation and foaming properties of hydrolysates derived from rapeseed
      isolate.
AB  - Two hydrolysis methods used to obtain rapeseed isolate derivates were compared:
      chemical hydrolysis performed under alkaline conditions and pepsic proteolysis
      performed under acidic conditions. The mean molecular weights obtained for the
      hydrolysates varied from 26 to 2.5 kDa, depending on the level of hydrolysis.
      Further characterisation showed that, at the same level of hydrolysis, the
      chemical hydrolysates differed by their charges and hydrophobicity from those
      derived from enzymatic digestion. Analysis of the foaming properties showed, for
      both cases, that a limited degree of hydrolysis, around 3%, was sufficient to
      optimise the foaming properties of the isolate despite the different
      physicochemical properties of the peptides generated. The study of foaming
      properties at basic, neutral and acidic pHs showed that the hydrolysate solutions
      yielded dense foams which drained slowly and which maintained a very stable
      volume under the three pH conditions tested.

PMID- 16581235
TI  - Luminal delivery and dosing considerations of local celecoxib administration to
      colorectal cancer.
AB  - The purpose of this study was to develop a biodegradable drug platform composed
      of chitosan and guar gum and to explore the possibility of using it for local
      adjuvant or neoadjuvant therapy of colorectal cancer. Celecoxib (Cx), a
      chemopreventative drug for familial adenomatous polyposis (FAP) and under trial
      for reducing post surgical colorectal malignancies, was selected as a model drug
      for this topical system because of the contraindications that are associated with
      its systemic administration. Films made of chitosan (Ct) and guar gum (GG) were
      prepared, characterized for equilibrium swelling, mucoadhesion, in vitro and in
      vivo degradation and loaded with Cx. Short term dosing studies in vitro were
      performed in the HT-29 colon carcinoma cell line that was incubated with Cx using
      the MTT test to assess IC50. The impact of a single high dose was evaluated and
      compared with a repeating low-dose regimen. In vivo dosing experiments with Cx
      were performed in the perfused intestine of the anaesthetized rat. Measuring
      tissue LDH assessed epithelium injury. Mechanical, mucoadhesion and in vitro
      degradation of the polysaccharide films were dictated by manipulating the ratios
      of Ct and GG. The addition of rat cecal contents to the dissolution medium
      increased the total Cx released from those films containing high amounts of GG.
      MTT reduction, a measure of cell proliferation, diminished as a function of
      increasing drug concentration and exposure time in the HT-29 cell line studies.
      Local high concentrations of Cx were shown to impede the proliferation of cancer
      cells directly, while chemoprevention has been demonstrated with low Cx doses.
      Healthy cells were shown to be sensitive to high Cx doses. Maximum therapeutic
      efficiency in the context of minimal healthy tissue exposure would thus be
      predicted utilizing a local delivery system such as the proposed adhesive,
      biodegradable polysaccharide composites.

PMID- 16581236
TI  - Is asthma research in dead end?
AB  - Despite enormous therapeutic advances, bronchial asthma remains a highly
      prevalent and serious health problem. Although we have learnt much about the
      pathogenesis of asthma and developed some new drugs within the last few years,
      there is still an urgent need for new treatments. The so-called single mediator
      approach appears to be ineffective in the treatment of asthma. Drugs with
      multiple sites of mode of action would have greater chances to be successfully
      introduced into therapy. The present drug screening strategy should be
      reconsidered and probably be replaced by new and more serendipity-based research.

PMID- 16581239
TI  - Fatty acid compositions of red blood cell phospholipids in children with autism.
AB  - We compared the compositions of fatty acids including n-3, n-6 polyunsaturated
      fatty acids, trans- and cis-monounsaturated fatty acids, and saturated fatty
      acids in the red blood cell membranes of 40 children with autism (20 with early
      onset autism and 20 with developmental regression) and age-matched, 20 typically
      developing controls and 20 subjects with non-autistic developmental disabilities.
      The main findings include increased levels of eicosenoic acid (20:1n9) and erucic
      acid (22:1n9) in autistic subjects with developmental regression when compared
      with typically developing controls. In addition, an increase in 20:2n6 and a
      decrease in 16:1n7t were observed in children with clinical regression compared
      to those with early onset autism. Our results do not provide strong evidence for
      the hypothesis that abnormal fatty acid metabolism plays a role in the
      pathogenesis of autism spectrum disorder, although they suggest some metabolic or
      dietary abnormalities in the regressive form of autism.

PMID- 16581237
TI  - Laser-microdissection for cell type- and compartment-specific analyses on genomic
      and proteomic level.
AB  - Morphological study and identification of cell differentiation within tissues are
      the basis for assessment of physiological and pathological processes. Applying
      molecular techniques, the analysis of tissue homogenates may lead to masking of
      genetic deviations or expression changes of an individual cell type by the bulk
      of surrounding cells. To overcome the tissue heterogeneity, cells have to be
      isolated selectively. Therefore, microdissection techniques were developed making
      retrieval of target cells simple, rapid and precise. Presenting an overview of
      our approaches, it is demonstrated that single cell isolation is often
      preconditional for the investigation of splicing isoform expression. To reveal
      gene regulation combining microdissection of few cells and real-time RT-PCR
      allows to determine relative mRNA expression in a cell type-specific manner, even
      after immunofluorescence staining of target cells. Combination with RNA
      preamplification techniques and micro arrays results in cell type- or compartment
      specific expression profiles that especially differ from those of tissue
      homogenates when minor represented cell types are investigated. For proteomic
      biomarker screening, the application of mass spectrometry techniques (SELDI/MALDI
      TOF) turned out to be feasible in combination with microdissected minute amounts
      of tissues. However, further identification of marker peaks still needs a
      remarkable effort. Strategies to deal with this problem are presented. In
      consequence, the isolation of cells or cell types allows a more accurate
      investigation of complex tissues and gives deeper insight to regulation processes
      and crosstalk of the respective cells.

PMID- 16581240
TI  - The impact of bronchiectasis associated to sinonasal disease on quality of life.
AB  - BACKGROUND: Bronchiectasis (BQs) is an uncommon disease with the potential to
      cause devastating complications. All patients with BQs have cough and chronic
      sputum production that may have a great impact on patient's quality of life.
      Upper airway symptoms are also frequent in patients with BQs. Associations
      between upper and lower airways diseases have been demonstrated in allergic
      rhinitis and asthma, nasal polyposis and asthma, chronic obstructive lung disease
      and chronic rhinosinusitis. OBJECTIVE: (1) To investigate the impact of
      bronchiectasis and nasal symptoms on quality of life. (2) To evaluate the added
      impact of nasal polyposis on quality of life in patients with BQs. METHODS: Sixty
      patients with bronchiectasis and upper airway symptoms were included. Patients
      were evaluated for nasal symptoms, nasal polyp size by endoscopy, and quality of
      life using the SF-36 generic questionnaire. RESULTS: In comparison with the
      Spanish general population, patients with BQs had worse scores in all SF-36
      domains (P<0.05). Males reported significantly higher quality of life scores on
      physical functioning and social functioning than females did. Although the age,
      pulmonary function, presence of nasal polyps, upper airway symptoms, tobacco
      smoking history, and disease duration was similar between them. Males with BQs
      had worse quality of life than males from the Spanish general population on body
      pain, general health, and vitality (P<0.05). Females with BQs had worse quality
      of life than females from the Spanish general population on physical function,
      body pain, general health, vitality, social function, and emotional role
      (P<0.05). Nasal polyps were found in 25 (41.6%) of 60 patients with BQs. No
      significant differences were observed on quality of life outcomes between
      patients with BQs with and without nasal polyposis. CONCLUSION: These results
      suggest that BQs has a considerable impact on quality of life while nasal
      polyposis has no additional impact on the quality of life of patients with BQs.

PMID- 16581241
TI  - The use of (micro)-X-ray absorption spectroscopy in cement research.
AB  - Long-term predictions on the mobility and the fate of radionuclides and
      contaminants in cementitious waste repositories require a molecular-level
      understanding of the geochemical immobilization processes involved. In this
      study, the use of X-ray absorption spectroscopy (XAS) for chemical speciation of
      trace elements in cementitious materials will be outlined presenting two examples
      relevant for nuclear waste management. The first example addresses the use of XAS
      on powdered cementitious materials to determine the local coordination
      environment of Sn(IV) bound to calcium silicate hydrates (C-S-H). Sn K-edge XAS
      data of Sn(IV) doped C-S-H can be rationalized by corner sharing binding of Sn
      octahedra to Si tetrahedra of the C-S-H structure. XAS was further applied to
      determine the binding mechanism of Sn(IV) in the complex cement matrix. The
      second example illustrates the potential of emerging synchrotron-based X-ray
      micro-probe techniques for elucidating the spatial distribution and the
      speciation of contaminants in highly heterogeneous cementitious materials at the
      micro-scale. Micro X-ray fluorescence (XRF) and micro-XAS investigations were
      carried out on Co(II) doped hardened cement paste. These preliminary
      investigations reveal a highly heterogeneous spatial Co distribution. The
      presence of a Co(II)-hydroxide-like phase Co(OH)2 and/or Co-Al layered double
      hydroxide (Co-Al LDH) or Co-phyllosilicate was observed. Surprisingly, some of
      the initial Co(II) was partially oxidized and incorporated into a Co(III)O(OH)
      like phase or a Co-phyllomanganate.

PMID- 16581242
TI  - Morphological and binding properties of interleukin-6 on thin ZnO films grown on
      (100) silicon substrates for biosensor applications.
AB  - To develop effective protein immobilization technology with minimal amounts of
      protein for high sensitivity surface acoustic wave biosensors, we determined the
      binding properties, and morphological characteristics of human interleukin-6 (IL
      6), a pro-inflammatory cytokine, on the surface of ZnO, and SiO(2) films grown
      onto (100) Si substrates, for the first time. Interleukin-6 was immobilized in
      the range of 0.276-10 pg/ml on the surface of ZnO and SiO(2), and visualized at
      each stage, while protein-protein interactions were measured with the
      antigen/antibody immunoassay of solid-phase ELISA, which we modified for these
      types of substrates. A relative mass value was determined in each case. ELISA
      detected upward of 1 and 6 ng/ml of protein applied on ZnO and SiO(2),
      respectively. It is concluded that the more reactive ZnO surface is a new and
      more effective template for protein immobilization.

PMID- 16581244
TI  - Effects of electromagnetic field on the batch cultivation and nutritional
      composition of Spirulina platensis in an air-lift photobioreactor.
AB  - Spirulina platensis was batch cultivated in a novel 3.5l magnetic air-lift
      photobioreactor with external-loop on which 0-0.55 T electromagnetic field (EMF)
      was imposed to investigate the EMF effects on the algal growth and nutrition
      composition. At the same time, the correlative mechanism was discussed mainly
      based on C, N, P uptake. It was found that, EMF has double-side effects on S.
      platensis cultivation depend on EMF intensity. 0.25 T EMF stress was found to be
      suitable for the algal cultivation enhancement increasing the maximum cell dry
      weight by 22% in a time period two days less than that of the control at 35
      degrees C and 252 micromol photonsm(-2)S(-1). In addition, the nutritional
      composition of S. platensis was improved in both essential amino acids such as
      histidine and trace elements Ni, Sr, Cu, Mg, Fe, Mn, Ca, Co and V. It was
      suggested it was possible to optimize the cultivation process of S. platensis by
      imposing suitable weak EMF which may enhance the nutrition assimilation e.g. C,
      N, P and minerals by S. platensis.

PMID- 16581243
TI  - Enhancement of seed vigour following insecticide and phenolic elicitor treatment.
AB  - Thiamethoxam (CGA 293'343) is a novel broad-spectrum neonicotinoid insecticide.
      It is commercially used as a seed treatment under the trademark Cruiser (CRZ).
      Although many reports detail its insecticidal, plant-protecting properties, there
      are minimal reports concerning the effect on seed germination activities which
      can be key control points of seedling vigour. In this report, we investigated the
      effect of CRZ, fish protein hydrolysates (FPH; a known elicitor of pentose
      phosphate pathway) and the combination of CRZ and FPH (CF) on seed vigour of pea,
      soybean and corn. Seed vigour was investigated by estimating germination
      percentage, shoot height, shoot weight, total soluble phenolic content,
      antioxidant content, G6PDH (glucose-6-phosphate dehydrogenase) activity, and GPX
      (guaiacol peroxidase) activity. Addition of FPH to CRZ (CF) seemed to have a
      slightly positive effect on seed vigour, especially, CF and FPH treatment for
      corn and FPH treatment for pea, suggesting that pre-sowing treatments may cause
      positive/negative effects on seed vigour, depending on the concentration of
      treatments. Further research will be needed to determine their effects and the
      optimal concentration for seed priming.

PMID- 16581246
TI  - Two novel furan derivatives from Phellinus linteus with anti-complement activity.
AB  - Two novel stereoisomers of furan derivatives, phellinusfurans A (1) and B (2),
      were isolated from the fruiting body of Phellinus linteus. Their structures were
      elucidated by spectroscopic analysis. Compounds 1 and 2 exhibited significant
      anti-complement activity with IC50 values of 33.6 and 33.7 microM, respectively,
      in inhibiting the hemolytic activity of human serum against erythrocytes.

PMID- 16581245
TI  - Substituted pyrrolidine-2,4-dicarboxylic acid amides as potent dipeptidyl
      peptidase IV inhibitors.
AB  - A series of substituted pyrrolidine-2,4-dicarboxylic acid amides were synthesized
      as potential antidiabetic agents, and many of them showed good in vitro DPP-IV
      inhibition (IC50 = 2-250 nM) with selectivity over DPP-II, DPP8, and FAP enzymes.
      Selected compounds 8c and 11a showed in vivo plasma DPP-IV inhibition after oral
      administration in Wistar rats.

PMID- 16581247
TI  - 1,1'-Xylyl bis-1,4,8,11-tetraaza cyclotetradecane: a new potential copper
      chelator agent for neuroprotection in Alzheimer's disease. Its comparative
      effects with clioquinol on rat brain copper distribution.
AB  - Dysfunction of copper metabolism leading to its excess or deficiency results in
      severe ailments. Recently, neurodegenerative disorders such as Alzheimer's
      disease have been associated with copper metabolism. Compounds having the ability
      to reduce copper levels in brain or to affect its distribution could have
      neuroprotective effects, mainly through a downregulation of the transcription of
      amyloid peptide precursor (APP). We report here the biological effect of compound
      1,1'-xylyl bis-1,4,8,11-tetraaza cyclotetradecane, which specifically affects
      copper concentration in the brain cortex region. Its copper homeostatic activity
      is compared with that of clioquinol, a well-known drug, which has been recently
      reported as an active A beta-peptide clearance drug in vivo for Alzheimer's
      patients.

PMID- 16581248
TI  - Synthesis of 2-alkoxy-8-hydroxyadenylpeptides: towards synthetic epitope-based
      vaccines.
AB  - The preparation of three different 2-alkoxy-8-hydroxyadenylpeptide conjugates has
      been accomplished by solid-phase synthesis combined with 'on-resin' Cu(I)
      catalyzed Huisgen cycloaddition. The immunogenicity of the compounds has been
      evaluated in IL-12 production and antigen presentation assays.

PMID- 16581249
TI  - Gankyrin: a new oncoprotein and regulator of pRb and p53.
AB  - Gankyrin is a new oncoprotein with potent cell cycle and apoptotic properties
      that is overexpressed early in hepatocarcinogenesis and in hepatocellular
      carcinomas. Gankyrin regulates the phosphorylation of the retinoblastoma protein
      (pRb) by CDK4 and enhances the ubiquitylation of p53 by the RING ubiquitin ligase
      MDM2. Purified preparations of the 26S proteasome contain gankyrin, which
      specifically interacts with the S6b (Rpt3) ATPase of the 19S regulator. In
      conclusion, gankyrin is a small versatile cell cycle regulator that illustrates
      the essential interplay between the ubiquitin proteasome system and gene
      expression in the cell. Here, we discuss the activities of gankyrin and present a
      model for its function in the regulation of pRb and p53.

PMID- 16581251
TI  - The preponderance of P450s in the Mycobacterium tuberculosis genome.
AB  - The genome of Mycobacterium tuberculosis (Mtb) encodes 20 different cytochrome
      P450 enzymes (P450s). P450s are mono-oxygenases, which are historically
      considered to facilitate prokaryotic usage of unusual carbon sources. However,
      their preponderance in Mtb strongly indicates crucial physiological functions, as
      does the fact that polycyclic azoles (known P450 inhibitors) have potent anti
      mycobacterial effects. Recent structural and enzyme characterization data reveal
      novel features for at least two Mtb P450s (CYP121 and CYP51). Genome analysis,
      knockout studies and structural comparisons signify important roles in cell
      biology and pathogenesis for various P450s and redox partner enzymes in Mtb.
      Elucidation of structure, function and metabolic roles will be essential in
      targeting the P450s as an 'Achilles heel' in this major human pathogen.

PMID- 16581250
TI  - p130Cas: a versatile scaffold in signaling networks.
AB  - The Cas family of multiadaptor and scaffold molecules has an essential role in
      intracellular signaling events. Although these proteins do not have enzymatic or
      transcriptional activity, they spatially and temporally control signaling events
      through their ability to undergo changes in phosphorylation and to associate with
      effectors proteins in multimolecular complexes. The involvement of p130Cas in
      cell motility as a component of the integrin signaling machinery is well
      established. Here, we discuss recent developments that highlight a fundamental
      role in cell transformation and microbial pathogenesis and the implications of
      these developments on p130Cas function under normal and pathological conditions.

PMID- 16581252
TI  - Evaluation of glycolamide esters of indomethacin as potential cyclooxygenase-2
      (COX-2) inhibitors.
AB  - A number of novel indomethacin glycolamide esters were synthesized and tested for
      their cyclooxygenase (COX-1 and COX-2) inhibition properties in vitro. Many of
      these compounds proved to be selective COX-2 inhibitors, and subtle structural
      changes in the substituents on the glycolamide ester moiety altered the
      inhibitory properties as well as potencies significantly. Their in vitro data
      were rationalized through molecular modeling studies. Few of them displayed anti
      inflammatory activity in vivo. Compound 32, [1-(4-chlorobenzoyl)-5-methoxy-2
      methyl-1H-indol-3-yl]acetic acid 2-morpholin-4-yl-2-oxo ethyl ester, was
      identified as a promising compound in this class and its good anti-inflammatory
      activity was demonstrated in the in vivo model.

PMID- 16581253
TI  - 3'-Fluoro-3'-deoxy-5'-noraristeromycin derivatives: synthesis and antiviral
      analysis.
AB  - The promising antiviral properties of 3'-fluoro-3'-deoxyadenosine and 4',4'
      difluoro-4'-deoxy-5'-noraristeromycin prompted the synthesis of the corresponding
      3'-fluoro derivatives of 5'-noraristeromycin. These target compounds, which were
      prepared from the same readily accessible cyclopentenol, were found to be
      inactive when subjected to 31 viral assays. The results have some implications on
      the mechanism of antiviral action of 5'-noraristeromycin and provide guidance for
      future geminal-difluoro analog design.

PMID- 16581254
TI  - Novel antibiotics: C-2 symmetrical macrocycles inhibiting Holliday junction DNA
      binding by E. coli RuvC.
AB  - Holliday junctions (HJs) are formed as transient DNA intermediates during site
      specific and homologous recombination. Both of these genetic exchange pathways
      are critical for normal DNA metabolism and repair. Trapping HJs leads to
      bacterial cell death by preventing proper segregation of the resulting
      interlinked chromosomes. Macrocyclic peptides designed to target this
      intermediate were synthesized with the goal of identifying compounds with
      specificity for this unique molecular target. We discovered ten macrocycles, both
      hexameric and octameric peptides, capable of trapping HJs in vitro. Those
      macrocycles containing tyrosine residues proved most effective. These data
      demonstrate that C-2 symmetrical macrocycles offer excellent synthetic targets
      for the development of novel antibiotic agents. Furthermore, the active compounds
      identified provide valuable tools for probing different pathways of
      recombinational exchange.

PMID- 16581255
TI  - Endophytic colonization of date palm (Phoenix dactylifera L.) leaves by
      entomopathogenic fungi.
AB  - Light and scanning electron microscopy together with fungal isolation techniques
      were used to detect entomopathogenic fungi within young and adult date palm
      (Phoenix dactylifera) petioles and to assess fungal survival in leaf tissues. The
      entomopathogenic fungi Beauveria bassiana, Lecanicillium dimorphum and
      Lecanicillium c.f. psalliotae survived inside leaf tissues at least 30 days after
      inoculation. Entomopathogenic fungi colonized inoculated petioles endophytically
      and were recovered up to 3cm from the inoculation site. Fungi were detected
      inside the parenchyma and sparsely within vascular tissue using microscopy
      techniques. Our results show that the entomopathogenic fungi used in this study
      survived and colonized date palm tissues in bioassays both under laboratory and
      field experimental conditions with no evidence of significant damage.

PMID- 16581256
TI  - Absolute activity measurement of the electron-capture-based radionuclides 139Ce,
      125I, 192Ir and 65Zn by liquid scintillation coincidence counting.
AB  - Four radionuclides with electron-capture-based decay schemes have been directly
      measured by a liquid scintillation coincidence extrapolation technique. 125I,
      192Ir and 65Zn were measured as part of international key comparisons held under
      the auspices of the International Bureau of Weights and Measures (BIPM). The
      139Ce measurements formed part of a regional comparison organized by the Asia
      Pacific Metrology Programme (APMP). Since 139Ce decays purely by electron
      capture, the basic method is described for this radionuclide. Results and
      difficulties encountered are discussed and uncertainty budgets are presented.

PMID- 16581257
TI  - Developing a VATS lobectomy programme--can VATS lobectomy be taught?
AB  - OBJECTIVE: Although VATS lobectomy has been demonstrated to be safe and
      effective, the technique is not widely practiced. This may, in part, reflect
      difficulty in acquiring appropriate skills. We have evaluated the effect of
      experience and training on surgical outcomes during the development and
      establishment of a VATS lobectomy programme. METHODS: Data were collected
      prospectively on 276 consecutive VATS lobectomies under the care of a single
      consultant as either the primary surgeon or supervising four trainees. The series
      was divided into cohorts of 46 patients. These comprised one trainee cohort and
      five sequential consultant cohorts. Statistical analysis utilised standard tests
      of significance. RESULTS: Increasing experience with the VATS lobectomy programme
      was associated with a significant reduction in operating time but intraoperative
      blood loss and postoperative stay were not influenced by increasing consultant
      surgical experience. Training was associated with a mean increase of 22 min
      operative time (p=0.0005) but no increase in intraoperative blood loss,
      morbidity, mortality or postoperative stay. The 46 trainee operative times were
      similar to the first 46 consultant cases. CONCLUSIONS: VATS lobectomy can be
      safely taught to trainee thoracic surgeons. However, in view of the limited
      number of centres undertaking VATS lobectomy, training should be coordinated at a
      national level to concentrate experience and improve uptake of this technique.

PMID- 16581258
TI  - The use of gabapentin for post-operative and post-traumatic pain in thoracic
      surgery patients.
AB  - OBJECTIVE: The pain following thoracic surgery and trauma is often refractory to
      conventional analgesic strategies. However, it shares key characteristics with
      neuropathic pain which gabapentin, an anticonvulsant, has been proven to
      effectively treat. To our knowledge, this is the first prospective study
      assessing the use of gabapentin in cardiothoracic surgery patients. METHODS:
      Gabapentin was prescribed to 60 consecutive out-patients with refractory pain
      persisting at four weeks or more after thoracic surgery or trauma. Follow-up of
      45 patients (75%) was performed for a median of 21 months (range: 12-28), and
      clinical data collected prospectively. The mean age of these patients was 51.6
      years (range 22-83). Of these 45 patients, 22 had received video-assisted
      thoracic surgery (VATS), 8 had received thoracotomy, 3 had received median
      sternotomy, and 12 were treated for blunt chest trauma. RESULTS: The mean
      duration of pre-treatment refractory pain was 5.76 months (range 1-62). The mean
      duration of gabapentin use was 21.9 weeks (range 1-68). No deaths or major
      complications were encountered. Minor side effects-mostly somnolence and
      dizziness-occurred in 18 patients (40.0%), causing 3 patients (6.7%) to
      discontinue gabapentin. Overall, 33 patients (73.3%) noted reduction of pain.
      Chest wall paresthesia distinguishable from wound pain was relieved in 24 (75.0%)
      of 32 affected patients. Severe initial pain was significantly correlated with
      pain relief using gabapentin (p=0.009). No other demographical or clinical
      variable correlated with benefit or side effects. Satisfaction with gabapentin
      use was expressed by 40 patients (88.9%). Side effects were not a source of
      dissatisfaction in any patient. CONCLUSIONS: Gabapentin appears safe and well
      tolerated when used for persistent post-operative and post-traumatic pain in
      thoracic surgery patients, although minor side effects do occur. Gabapentin may
      relieve refractory chest wall pain in some of these patients, particularly those
      with more severe pain. Further studies are warranted to define the role of
      gabapentin in cardiothoracic surgical practice.

PMID- 16581259
TI  - A questionnaire study investigating the prevalence of the neuropathic component
      of chronic pain after thoracic surgery.
AB  - OBJECTIVE: Our questionnaire study set out to assess the prevalence of chronic
      pain after thoracic surgery, the contribution of the neuropathic component of
      chronic pain and the impact of chronic pain on patients' lives. METHODS: A
      questionnaire was sent to 1152 patients who had undergone thoracic surgery in our
      department between 7 months and 7 years ago. The questionnaire was designed
      specifically for the study and included questions on neuropathic symptoms.
      Responses were correlated with data from our prospectively entered database for
      analysis. RESULTS: Nine hundred and forty-eight people were included in the
      study, of which 600 responded (63%). Prevalence of chronic pain is 57% at 7-12
      months, 36% at 4-5 years and 21% at 6-7 years. Patient age, consultant and time
      since the operation all have significant effects. Surgical approach (video
      assisted thoracoscopic surgery, thoracotomy) and diagnosis are not significant.
      Thirty-nine percent of those with pain take analgesia, 46% felt their pain is
      their worst medical problem and 40% reported it limits their daily activities.
      The prevalence of each neuropathic symptom is between 35 and 83%. The presence of
      a neuropathic symptom is associated with significantly more severe pain, more
      analgesia use and pain more likely to limit daily activity. CONCLUSIONS: Chronic
      pain has a significant prevalence and impact on patients' lives for several years
      after thoracic surgery. Nerve dysfunction is associated with more severe pain, a
      greater impact and tends to persist. The reason for the individual consultant
      being an important factor in post-thoracotomy pain needs further investigation.

PMID- 16581260
TI  - Differential, time-dependent effects of perivenous application of fibrin glue on
      medial thickening in porcine saphenous vein grafts.
AB  - OBJECTIVE: Neointimal and medial thickening play a critical role in late vein
      graft failure following CABG. Previous ex vivo experiment suggested that
      perivenous application of fibrin glue may reduce the damage in the circular
      smooth muscle cell layer of the media of the vein graft shortly after exposing to
      arterial pressure. However, the in vivo as well as the longer term impact of this
      intervention remain unknown. METHODS: Bilateral saphenous vein-carotid artery
      interposition grafting was performed in eight large white pigs (35-45 kg). In
      each pig, one of the grafts was randomly selected to receive perivenous fibrin
      glue support while the contralateral graft served as control. At 1 and 4 months
      following surgery (n=4 pigs in each group), all 16 patent vein grafts were
      removed and pressure-fixed. Multiple histological sections from each graft were
      prepared. Proliferating cell nuclear antigen (PCNA) was detected by
      immunocytochemistry. Vein graft morphology was assessed using computer-aided
      planimetry. RESULTS: Although perivenous application of fibrin glue had little
      effects either on medial thickness 1 month after implantation or on PCNA index,
      it significantly increased medial thickness (control: 0.37+/-0.02 mm; treated:
      0.55+/-0.02 mm, p<0.001) and total wall thickness (control: 0.75+/-0.04 mm;
      treated: 0.92+/-0.04 mm, p=0.008) at 4 months (mean+/-SEM; n=4 in each group).
      CONCLUSIONS: Our data indicated that perivenous application of fibrin glue
      enhances graft thickening and as such does not constitute a strategy for
      preventing late vein graft failure after CABG.

PMID- 16581261
TI  - Risk assessment and early outcome following the Norwood procedure for hypoplastic
      left heart syndrome.
AB  - BACKGROUND: This study was undertaken to identify risk factors for early
      mortality following the Norwood procedure for hypoplastic left heart syndrome
      (HLHS) and develop a predictive risk model to monitor clinical performance.
      METHODS AND RESULTS: Between December 1992 and June 2004, 333 patients with HLHS
      underwent a Norwood procedure at a single institution. The early mortality was
      29% (n=95). Estimated early mortality improved progressively and was 10% at the
      end of the series. Multivariable analysis identified that body surface area at
      operation, size of the ascending aorta, preoperative right ventricular function
      and source of pulmonary blood flow established at operation were risk factors for
      early mortality (P<0.05). These variables were included in a preoperative risk
      model. The duration of cardiopulmonary support was an independent risk factor,
      which was included in a separate operative risk model. The performance of the
      risk models was evaluated by goodness-of-fit analyses, using the Hosmer-Lemeshow
      test and receiver operating characteristic (ROC) curve. Both models were well
      calibrated across all deciles (P=0.64, P=0.77) and discriminated moderately well.
      The area under the ROC curve was 0.71 for Model 1 and 0.75 for Model 2. Risk
      adjustment broadly accounted for the variation in early mortality observed during
      this series. CONCLUSIONS: Patient-related and predetermined operative variables
      have a major influence on the early outcome following the Norwood procedure for
      HLHS. The identification of these risk factors allows the risk of early mortality
      to be calculated. This information could be applied as part of a risk-adjusted
      performance-monitoring system to enable early identification of meaningful
      changes in practice.

PMID- 16581262
TI  - Role of endogenous hydrogen peroxide in cardiovascular ischaemia/reperfusion
      function: studies in mouse hearts with catalase-overexpression in the vascular
      endothelium.
AB  - Hydrogen peroxide (H2O2) has been implicated as a component of oxidative
      ischaemia/reperfusion stress. We investigated the role of H2O2 in cardiovascular
      ischaemia/reperfusion stress in hearts from mice overexpressing catalase in their
      endothelial cells. Hearts of transgenic (TG, n = 9) and age-matched wild-type
      (WT, n = 7) mice were perfused at constant flow (2.2 mlmin(-1)) and subjected to
      brief ischaemia and reperfusion. Intrinsic function and the effects of
      norepinephrine (3 nM-3 microM) were determined. Left ventricular pressure
      (LVDevP; balloon method), end-diastolic pressure (LVEDP), maximum rates of
      pressure development (+dP/dt, -dP/dt), coronary perfusion pressure (index of
      vascular function) and heart rate were recorded. Apart from a slightly higher
      recovery of LVDevP during reperfusion (+6 mmHg), neither systolic nor diastolic
      function was improved during ischaemia or reperfusion in TG hearts. However,
      hearts from TG mice exhibited a significantly better contractile response to
      noradrenergic stimulation (LVDevP: +20 mHg or 1.15-fold increase; +dP/dt: +1476
      mmHgs(-1) or 1.2-fold increase) (P < 0.05). Norepinephrine relaxed the coronary
      microvasculature and increased heart rate, but no differences were detected
      between groups. We conclude that overexpressing catalase in endothelial cells is
      only weakly protective against myocardial or vascular ischaemia/reperfusion
      injury, but preserves the responsiveness of the heart to adrenergic stimulation.

PMID- 16581263
TI  - Pathogen inactivation and removal procedures used in the production of
      intravenous immunoglobulins.
AB  - Patients with immunodeficiencies or some types of autoimmune diseases rely on a
      safe therapy with intravenous immunoglobulins (IVIGs) manufactured from human
      plasma, the only available source for this therapeutic. Since plasma is
      predisposed to contamination by a variety of blood-borne pathogens, ascertaining
      and ensuring the pathogen safety of plasma-derived therapeutics is a priority
      among manufacturers. State-of-the-art manufacturing processes provide a high
      safety standard by incorporating virus elimination procedures into the
      manufacturing process. Based on their mechanism these procedures are grouped into
      three classes: partitioning, inactivation, and virusfiltration.

PMID- 16581264
TI  - Sir Richard Doll, 1912 to 2005: a tribute and personal remembrance.

PMID- 16581265
TI  - Blood exposure among paramedics: incidence rates from the national study to
      prevent blood exposure in paramedics.
AB  - PURPOSE: The aim of the study is to estimate incidence rates of occupational
      blood exposure by route of exposure (needlesticks; cuts from sharp objects;
      mucous membrane exposures to the eyes, nose, or mouth; bites; and blood contact
      with nonintact skin) in US and California paramedics. METHODS: A mail survey was
      conducted in a national probability sample of certified paramedics. RESULTS:
      Proportions of paramedics who reported an exposure in the previous year were
      21.6% (95% confidence interval [CI], 17.8-25.3) for the national sample and 14.8%
      (95% CI, 12.2-17.4) for California. The overall incidence rate was 6.0/10,000
      calls (95% CI, 3.9-8.1). These rates represent more than 49,000 total exposures
      and more than 10,000 needlesticks per year among paramedics in the United States.
      Rates for mucocutaneous exposures and needlesticks were similar (approximately
      1.2/10,000 calls). Rates for California were one third to one half the national
      rates. Sensitivity analysis showed that potential response bias would have little
      impact on the policy and intervention implications of the findings. CONCLUSION:
      Paramedics continue to be at substantial risk for blood exposure. More attention
      should be given to reducing mucocutaneous exposures. The impact of legislation on
      reducing exposures and the importance of nonintact skin exposures need to be
      better understood.

PMID- 16581266
TI  - Juicy fruit and creepy crawlies: an electrophysiological study of the implicit
      Go/NoGo association task.
AB  - The Go/NoGo association task (GNAT) has been used in behavioral studies to
      measure the strength of association between different category groups and two
      poles of an evaluative dimension. However, reaction time data do not provide
      information about the neural time course of such associative information. We
      investigated event-related brain potentials (ERPs) elicited when participants
      were required to respond (Go) or withhold a response (NoGo) according to task
      instructions. Task instructions paired words from one of two taxonomic categories
      (fruit/bugs) with either pole of an evaluative dimension (good/bad). Within a
      given run, Go responses were assigned to one of the categories and one evaluative
      dimension. ERPs showed an increased negativity over frontal sites to NoGo as
      compared to Go responses. Moreover, NoGo minus Go difference waves showed that
      the N200 effect was delayed in trials within incongruent blocks (e.g., "Press if
      a bug word or a good word") as compared to trials within congruent blocks (e.g.,
      "Press if a bug word or a bad word"). These results suggest that such associative
      attitude information is available at a very early stage of processing, less than
      250 ms after seeing a fruit or a bug word. This finding is further discussed with
      respect to alternative explanations of the behavioral effect.

PMID- 16581267
TI  - Hybridization in coral reef fishes: introgression and bi-directional gene
      exchange in Thalassoma (family Labridae).
AB  - Hybrids in coral reef fishes have traditionally been described based on external
      features using meristic characters and colouration to identify putative parental
      contributors. This study utilised molecular genetic techniques to verify hybrid
      status and identify putative parental species for five hybrid specimens
      (Labridae: Thalassoma) collected from Holmes Reef in the Coral Sea. Phylogenetic
      analyses support hybrid origins of the specimens. Mitochondrial COI gene, nuclear
      S7 (intron 1) and nuclear copy of mitochondrial (NUMT) D-loop region corroborate
      the identity of T. quinquevittatum as the maternal and T. jansenii as the
      paternal contributor. Backcrossing to parental species by hybrids and bi
      directional gene exchange between the Holmes Reef populations of T. jansenii and
      T. quinquevittatum was detected, suggesting that hybrids are fertile and able to
      reproduce successfully. F(1) hybrids display a mixture of the colouration
      attributes of the two parental species, but subsequent backcrossed individuals
      were unrecognisable as hybrids and displayed colouration of either parental
      species. A large numerical imbalance exists between the putative parental species
      at Holmes Reef, with T. quinquevittatum outnumbering T. jansenii by approximately
      25:1. In this case study, hybridization appears to be driven by ecological rather
      than evolutionary factors.

PMID- 16581268
TI  - Budding speciation and neotropical origin of the Azorean endemic liverwort,
      Leptoscyphus azoricus.
AB  - The origin of plant species endemism in Macaronesia, one of the 25 world
      biodiversity hotspots, has traditionally been either interpreted as a result of
      the dramatic reduction of a broader tertiary distribution range during the Ice
      Age or neoendemism. This hypothesis is tested here in the context of a species
      level phylogeny employing chloroplast trnL-trnF and atpB-rbcL sequences in the
      leafy liverwort genus Leptoscyphus (Lophocoleaceae). The data suggest that the
      Azorean endemic Leptoscyphus azoricus originated from parental populations of the
      Neotropical Leptoscyphus porphyrius by long-distance dispersal across the
      Atlantic and subsequent isolation. Possible reasons for the differences in the
      origin of endemism in angiosperms, wherein by far most endemic species have their
      close relatives on the European and North African continents, are discussed.

PMID- 16581269
TI  - A molecular phylogenetic perspective on the evolutionary history of Alosa spp.
      (Clupeidae).

PMID- 16581270
TI  - A novel approach to data processing of the QT interval response in the conscious
      telemetered beagle dog.
AB  - INTRODUCTION: Drug-induced QT interval prolongation may lead to ventricular
      arrhythmias. The aim of the study was to optimize QT interval data processing to
      quantify drug-induced QT interval prolongation in the telemetry instrumented
      conscious dog model. METHODS: The test substances cisapride, dofetilide,
      haloperidol, and terfenadine and corresponding vehicles were given to male and
      female beagle dogs during two consecutive 90-min intravenous infusions.
      Cardiovascular parameters were recorded for 24 h and exposure to the drugs was
      measured. The delayed response in the QT interval after an abrupt change in heart
      rate was investigated. Eight mathematical models to describe the QT interval
      heart rate relationship were compared and different sets of covariates were used
      to quantify the drug-induced effect on the QT interval. RESULTS: After an abrupt
      decrease in heart rate, a 75% adaptation of the QT interval was reached after
      54+/-9 s. A linear model was preferred to correct the drug-induced effect on the
      QT interval for heart rate, vehicle effect, serial correlation, plasma
      concentration and time of day. All test substances significantly prolonged the QT
      interval. DISCUSSION: To optimize the processing of QT interval data, the delay
      in QT interval response after an abrupt change in heart rate should be
      considered. The QT interval-heart rate relationship and vehicle response were
      individual-specific and corrections were therefore made individually. When
      estimating the drug-induced effect on the QT interval it is considered
      advantageous to use plasma concentration as a covariate, as well as adjusting for
      vehicle effect and serial correlation in measurements. The conscious dog model
      detected significant increases in the QT interval for all test substances
      investigated.

PMID- 16581271
TI  - A panic experimental model: validation of a complex operant behavioral method in
      undernourished rats, with desipramine to provide a template effect profile.
AB  - INTRODUCTION: Clinical studies have shown that some antidepressants may be more
      efficient than benzodiazepines to alleviate anxiety associated with panic
      disorders; however, operant conflict procedures in rats developed so far seem not
      particularly able to model human anxiety sensitive to antidepressant treatments.
      Previous panic models with learned responses did not statistically subtract the
      effect of confounding factors from the variable of interest. METHODS:
      Undernourished rats were selected due to their behavioral and neurobiological
      resemblance to human patients suffering from panic disorder. The Geller-Seifter
      paradigm represented the stressful environmental condition in adult life.
      Desipramine (10 mg/kg/day) or saline were administered IP during 7 days under a
      cross over design (N=10). Five daily 15 min-operant sessions were carried out on
      each experiment. Unpunished, unrewarded and punished operant behavioral periods
      were identical both in their duration and in their reward system (the FR1
      schedule) in order to measure response suppression, which has not been considered
      in previous studies with the Geller-Seifter paradigm. The dependent variable was
      the difference between comparable unpunished and punished periods. RESULTS: A
      significant Diet x Drug interaction was observed in the dependent variable, which
      represented the level of "suppression/suppression release" induced by treatments.
      DISCUSSION: Compared to control rats, deprived rats showed a significant and
      selective anticonflict effect of desipramine on the stressful and complex operant
      performance. The animal model of perinatally protein-deprived rats along with the
      Geller-Seifter's operant behavioral paradigm may represent a more sensitive
      approach to model human anxiety sensitive to antidepressant treatments by
      considering the combined impact of both early biological trauma and adult learned
      experiences under the same design.

PMID- 16581272
TI  - Mixtures of glucosamine and chondroitin sulfate reverse fibronectin fragment
      mediated damage to cartilage more effectively than either agent alone.
AB  - OBJECTIVE: To test the effectiveness of glucosamine (GluNH(2))-HCl, chondroitin
      sulfate (CS) and mixtures in protecting cartilage exposed to fibronectin
      fragments (Fn-fs), an exposure known to enhance catabolic cytokines and matrix
      metalloproteinases (MMPs). METHODS: Pharmacologic formulations of GluNH(2)
      (FCHG49) and CS (TRH122) (Nutramax Laboratories, Inc.) were added at 1, 10 or 100
      microg/ml singly or in mixtures to bovine cartilage cultures in serum or serum
      free conditions with or without Fn-f. Proteoglycan (PG) release into media and
      remaining cartilage PG content were measured by dye binding analysis and effects
      on PG synthesis by assays of 35-sulfate incorporation. Effects on MMP-3 and -13
      expression were measured by Western blotting of conditioned media. RESULTS: In
      serum-free conditions, the agents singly or as mixtures did not block Fn-f
      mediated matrix degradation. In serum, single agents were weakly effective at 100
      microg/ml, while the mixture of each agent at 0.1 microg/ml decreased PG loss by
      about 50% by day 7 and at 1 microg/ml restored nearly 50% of the PG after 7 days
      in Fn-f pretreated cartilage. However, both agents singly and as mixtures at 0.1
      100 microg/ml decreased MMP release. In serum, the single agents at 1-10
      microg/ml weakly reversed Fn-f mediated PG synthesis suppression, while the
      mixtures were 100% effective at 1 microg/ml. CONCLUSIONS: GluNH(2) and CS act
      synergistically in reversing damage and promoting repair at concentrations found
      in plasma after oral ingestion of these agents. Reversal of PG synthesis
      suppression correlates more with these activities than suppression of MMP-3 or 
      13 expression.

PMID- 16581273
TI  - True aneurysm of extracranial internal carotid artery in a 10-year-old.
AB  - INTRODUCTION: In this report, we describe a very unusual case, true aneurysm of
      the internal carotid artery, in a child. REPORT: A 10-year-old boy with a
      pulsating mass on his right neck was admitted with the diagnosis of a 25 mm by 50
      mm true aneurysm of the right internal carotid artery, which was resected, and a
      5-mm ePTFE graft was interposed. He was discharged on day 3 without
      complications. CONCLUSIONS: Prompt differential diagnosis of this pathology is
      crucially important. Open surgery yields acceptable results depending on the
      size, extension and the type of the aneurysm.

PMID- 16581274
TI  - Endothelial nitric oxide synthase genotype and haplotype are not associated with
      diabetic retinopathy in diabetes type 2 patients.
AB  - Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been
      associated with the development of diabetic retinopathy (DR) in patients with
      type 1 diabetes mellitus (T1DM), but not with T2DM. However, no previous study
      has analyzed combinations of genetic markers (haplotypes), which can be more
      informative. We studied three eNOS genetic polymorphisms: a single nucleotide
      polymorphism in the promoter region (T(-786)C), in exon 7 (Glu298Asp), and a
      variable number of tandem repeats in intron 4 (b/a) in 103 healthy controls, and
      in 170 patients with T2DM (without DR, N=114; with DR, N=56). We also examined
      the association of eNOS gene haplotypes with T2DM and with DR. No differences
      were found in the frequencies of genotypes and alleles of the three polymorphisms
      among the three groups of subjects. However, the "C-Glu-b" haplotype was more
      common in healthy controls (24%) than in T2DM patients (7%) (P=0.0001). Finally,
      no significant difference in the distribution of eNOS haplotypes frequencies was
      found when T2DM patients with or without DR were compared (P=0.7372). These
      findings suggest no association between DR and individual eNOS haplotypes in T2DM
      patients. The "C-Glu-b" haplotype, however, may have a protective effect against
      T2DM. Further studies should be conducted to address the molecular basis for such
      an effect.

PMID- 16581275
TI  - Collagen colocalizes with a protein containing a decorin-specific peptide in the
      tissues of the ascidian Styela plicata.
AB  - Decorin is an extracellular matrix dermatan sulfate/chondroitin sulfate
      proteoglycan found in a variety of vertebrate species. In the extracellular
      matrix of mammals, decorin interacts with fibrillar collagen and regulates its
      morphology. We report here the occurrence and distribution of collagen type I and
      the peptide, CEASGIGPEVPDDRD, which is present in the human decorin proteoglycan,
      in the extracellular matrix of different tissues of the primitive invertebrate
      chordate Styela plicata. The content of collagen was estimated by hydroxyproline,
      and its distribution in the tissues by histochemistry. Collagen was detected
      biochemically in intestine, heart, pharynx and mantle, occurring in higher
      amounts in the heart, followed by pharynx, mantle and intestine. Histochemical
      analysis with Sirius red indicates that collagen is present in the extracellular
      matrix of intestine and pharynx. Further ultrastructural immuno-gold assays using
      polyclonal antibodies raised against the decorin-specific peptide CEASGIGPEVPDDRD
      and collagen type I showed a co-localization of these molecules. These data
      suggest the occurrence of a protein containing a decorin-like peptide sequence,
      which may be interacting with fibrillar collagen in this primitive chordate.

PMID- 16581276
TI  - The fractional contributions of elementary modes to the metabolism of Escherichia
      coli and their estimation from reaction entropies.
AB  - The metabolism of a cell can be viewed as a weighted sum of elementary modes. Due
      to the multiplicity of modes the identification of the individual weights
      represents a non-trivial problem. To enable the determination of weighting
      factors we have identified and implemented two gene deletions in combination with
      defined growth conditions that limit the metabolism from 4374 original elementary
      modes to 24 elementary modes for a non-PHB synthesizing control and 40 modes for
      a PHB synthesizing strain. These remaining modes can be further grouped into five
      families that have the same overall stoichiometry. Thus, the complexity of the
      problem is significantly reduced, and weighting factors for each family of modes
      could be determined from the measurement of accumulation rates of metabolites.
      Moreover, it is shown that individual weights are inversely correlated with the
      entropy generated by the operation of the used pathways defined in elementary
      modes. This suggests that evolution developed cellular regulatory patterns that
      permit diversity of pathways while favoring efficient pathways with low entropy
      generation. Furthermore, such correlation provides a rational way of estimating
      metabolic fluxes based on the thermodynamic properties of elementary modes. This
      is demonstrated with an example in which experimentally determined, intracellular
      fluxes are shown to be highly correlated with fluxes computed based on elementary
      modes and reaction entropies. The analysis suggests that the set of elementary
      modes can be interpreted analogous to a metabolic ensemble of quantum states of a
      macroscopic system.

PMID- 16581277
TI  - Antimicrobial resistance of Pseudomonas aeruginosa in pediatric infections.

PMID- 16581278
TI  - Unrecognized near-fatal hyperlactatemia in an HIV-infected infant exposed to
      nucleoside reverse transcriptase inhibitors.

PMID- 16581279
TI  - New insights into function of red cell membrane proteins and their interaction
      with spectrin-based membrane skeleton.

PMID- 16581281
TI  - Generation of mice with inactivated Rh or Rhag genes.
AB  - Mice carrying inactivated Rh and Rhag genes were generated by insertional
      targeting. KO animals exhibited normal growth, development and fertility and both
      types were indistinguishable at a gross phenotypic level from their wild type
      littermates. Preliminary analysis revealed that red cells from Rh-/- mice lack Rh
      protein and have a moderate decrease of Rhag protein, whereas those from Rhag-/-
      mice have a total absence of Rhag and Rh proteins. Studies are in progress to
      delineate the antigenic, biochemical and functional abnormalities of red cells
      from these animals as well as the impact on hematological parameters and
      erythropoiesis.

PMID- 16581280
TI  - The 'metabolon,' CD47, and the 'phagocytic synapse': molecular co-localization
      and species divergence.
AB  - CD47 is a widely expressed integral membrane protein, found also on red blood
      cells where it reportedly has a key role in inhibiting phagocytic clearance of
      RBC by signaling within a multi-molecular 'phagocytic synapse'. Calreticulin is
      postulated to be on the RBC surface and stimulate phagocytosis, whereupon CD47 on
      the RBC binds SIRPalpha on the phagocyte and signals a block against
      phagocytosis. While studies of mouse suggest such an inhibitory role for CD47,
      CD47 seems to have distinct interactions in human RBC--particularly within a
      'metabolon' complex of CD47, Rh proteins, and several other proteins. We have
      assessed the relative density, co-clustering, and mobility of some of the
      implicated proteins on human RBC versus murine RBC (hu-RBC and mu-RBC,
      respectively), and we find a few major differences. While RBC from both species
      express similar densities of CD47 and SIRPalpha interactions are measurably
      modest, the interactions prove species-specific. While RBC from both species also
      have detectable calreticulin, fresh hu-RBC are found to have 10-100-fold more
      calreticulin binding sites on their surface. Imaging of clusters of SIRPalpha
      CD47 on both species of RBC show that RhD does co-localize with CD47 on hu-RBC,
      but neither calreticulin nor Glycophorin-A appear enriched in the metabolon
      complexes. Furthermore, mouse-cells alone tend to aggregate due to cross-bridging
      by SIRPalpha complexes, showing accumulation of CD47 in the adhesion zone, which
      is consistent with a high mobility of CD47 unique to mu-RBC.

PMID- 16581282
TI  - [Metastasis of a lumbosacral ependymoma with very long disease-free survival: a
      case report and review of the literature].
AB  - Ependymoma is rare glial tumour of the central nervous system and is considered
      to be low-grade. The lumbosacral location of spinal ependymoma is the most
      common. Prognosis of ependymomas is dependent on tumour location, histological
      subtype and differentiation, extent of the tumour and of the completeness of the
      surgical resection. One of the characteristics of this kind of tumour is to
      present the possibility of a seeding of the entire cerebrospinal axis, by the way
      of cerebrospinal liquid. We describe the case of a young male patient operated by
      incomplete resection of a lumbar ependymoma. Six months later, the patient's
      symptoms reappeared and an external radiotherapy at curative doses and
      chemotherapy were delivered. Evolution of the remaining tumour was diagnosed 6
      years after at the primary site and operated by large incomplete resection. A
      second session of radiotherapy was therefore administered. Twenty-four years
      after this episode, cervical pain and gait troubles appear. Complete imaging
      study concluded to a cervical extramedullary intradural tumour and to the
      persistence of the primary lumbosacral tumour. Macroscopical complete resection
      of the cervical tumour was performed and pathological findings concluded to a
      metastasis of his lumbar ependymoma. External radiotherapy was delivered on this
      site with a total dose of 50 Gy. Eight years after this episode, the patient is
      alive without evidence of distant disease. The primary lumbosacral ependymoma is
      stable. Ependymomas are often recurrent at the primary site, but can seed on the
      entire cerebrospinal axis. Awareness of such aberrant tumoral behaviour, even
      after such a long disease free interval, may warrant more careful follow-up of
      patients with this diagnosis.

PMID- 16581283
TI  - [Assessment of human papillomavirus testing on liquid-based Cyto-screen system
      for women with atypical squamous cells of undetermined significance. Effect of
      age].
AB  - OBJECTIVE: Analyse the performance of human papillomavirus testing with hybrid
      capture II on liquid-based CYTO-screen system for women diagnosed with atypical
      squamous cells of undetermined significance according to the age. PATIENTS AND
      METHODS: Were included all women diagnosed with atypical squamous cells of
      undetermined significance for whom human papillomavirus testing was performed and
      cytological and histological procedures were available over a follow-up period of
      6 to 18 months. RESULTS: Human papillomavirus testing was performed in 3,047
      patients, and results were compared to cytological and histological follow-up
      diagnosis in 1,880 cases (61.7%). The sensitivity for diagnosing cervical
      intraepithelial neoplasia was 93.3% in women less than 30 of age and 89.7% in
      women more than 30 of age. Specificity was 44.9% in women less than 30 of age and
      64.4% in women more than 30 of age. Likelihood ratios confirmed these results as
      they show a low discriminatory power in case of positive result specifically in
      women less than 30 of age but an excellent performance in case of negative
      result. DISCUSSION AND CONCLUSION: The use of human papillomavirus testing after
      a diagnosis of atypical squamous cells of undetermined significance with the
      residual material of Cyto-screen system is a possible triage procedure to
      identify patients needing a colposcopy. Its specificity is better for women over
      30.

PMID- 16581284
TI  - Computational fluid dynamics modeling of insertion and advancement of a reamer
      into the intramedullary canal of a long bone.
AB  - The effect of reaming velocity on the pressure distribution within the bone was
      investigated numerically by solving the full three-dimensional momentum equations
      together with the continuity equation using the finite element technique.
      Viscosity was also varied to obtain a pressure envelope. It was found that all
      the experimental data follow the same trends as the envelopes predicted by the
      finite element model. It was clear that an increase in either the implant
      insertion rate or the viscosity resulted in an increase in pressure in the
      intramedullary canal.

PMID- 16581285
TI  - Is availability of public open space equitable across areas?
AB  - This study examined whether availability of public open spaces that can be used
      for recreation varies according to neighbourhood socio-economic disadvantage.
      Density and area of public open spaces were examined using a geographic
      information system and postal boundaries were used to define neighbourhoods.
      Neighbourhood socio-economic status (SES) was stratified into quintiles. Once
      neighbourhood population and geographic area were considered there were no
      differences in the number or total area of free-access, restricted access or
      sporting/recreation open spaces across quintiles of neighbourhood SES. Future
      research should examine whether the quality of public open spaces differ by
      neighbourhood SES.

PMID- 16581286
TI  - Screening for drug-induced spoliation of the hydrogel optic of the AlphaCor
      artificial cornea.
AB  - Clinical experience and in vitro investigations demonstrated that AlphaCor, a
      hydrogel keratoprosthesis, can undergo both surface spoliation and internal
      depositions/colourations after exposure to certain medications, alone or in
      combination. While the most commonly used medications have not been associated
      with spoliation in vivo, many medications are reportedly used due to the complex
      co-pathologies in many recipients, and regional variations in available
      medications. We screened a number of drugs used or proposed by surgeons for use
      in AlphaCor patients to evaluate their potential to cause visually significant
      optic spoliation (surface or intragel, or colour changes). Poly(2-hydroxyethyl
      methacrylate) discs with an identical composition to AlphaCor's optic were
      incubated with each medication and then with simulated aqueous humour (SAH) at 37
      degrees C for 7 days. They were then examined under magnification and by
      histology (selected samples). Clinical feedback for the test medications was
      reviewed and compared with the in vitro results. A minority of the drugs caused
      surface spoliation (TobraDex, Prednefrin Forte, Azopt) or colour staining
      (including Zymar, Vigamox, Quixin) when tested alone, but SAH appeared to promote
      hydrogel cloudiness and surface deposits. The in vitro spoliation occurred more
      frequently than in vivo reports of spoliation in recipients of the same
      medications. This study is consistent with earlier findings in demonstrating
      involvement of topical medications in hydrogel spoliation, although a much lower
      incidence of spoliation is reported for AlphaCor in human recipients than
      indicated by the laboratory findings. The interactions of biological fluids and
      drugs require further study.

PMID- 16581287
TI  - Biosynthetic diversity in plant triterpene cyclization.
AB  - Plants produce a wealth of terpenoids, many of which have been the tools of
      healers and chiefs for millennia. Recent research has led to the identification
      and characterization of many genes that are responsible for the biosynthesis of
      triterpenoids. Cyclases that generate sterol precursors can be recognized with
      some confidence on the basis of sequence; several catalytically important
      residues are now known, and the product profiles of sterol-generating cyclases
      typically reflect their phylogenetic position. By contrast, the phylogenetic
      relationships of cyclases that generate nonsteroidal triterpene alcohols do not
      consistently reflect their catalytic properties and might indicate recent and
      rapid catalytic evolution.

PMID- 16581288
TI  - Integrative analysis of metabolic networks: from peaks to flux models?
AB  - Recent developments in genomic and post-genomic technologies have led to the
      amassment of data describing genome sequences, transcript, protein and metabolite
      abundances, protein modifications, and protein-protein and protein-DNA
      interactions. Such technologies have vastly expanded the inventory of detectable
      molecular species and can be used to describe their interdependence, but they
      have yet to fulfill their promise in enhancing our knowledge of how flux through
      metabolic pathways is regulated. A convergence of traditional reductionistic and
      novel holistic experimental approaches could aid in elucidating flux control.

PMID- 16581289
TI  - Spectrophotometric studies of complexation of [60]fullerene with series of
      aromatic hydrocarbon molecules containing flexible phenyl substituents.
AB  - The absorption spectra of the electron donor-acceptor complexes of [60]fullerene
      with five different aromatic hydrocarbon (AH) molecules containing flexible
      phenyl substituents have been investigated in toluene medium. An absorption band
      due to charge transfer (CT) transition is observed in each case in the visible
      region. The experimental CT transition energies are well correlated with the
      vertical ionization potentials of the AHs studied (through Mulliken's equation)
      from which we extract degrees of charge transfer, oscillator and transition
      dipole strengths of the CT complexes. The degrees of CT in the ground state of
      the complexes have been found to be very low (0.49-0.55%). The formation
      constants (K) for the complexes of [60]fullerene with the aromatic hydrocarbons
      have been determined by UV-vis spectroscopy. Both K values and PM3 calculations
      on [60]fullerene/AH complexes reveal that nature of substitution in the donor
      moiety as well as steric compatibility with the acceptor molecule govern the
      process of EDA complex formation.

PMID- 16581290
TI  - Completing the cycles; the dynamics of endonuclear lipidomics.
AB  - Signal transductions via periodic generation and mobilisation of lipid second
      messengers within the nuclear matrix of eukaryotic cells have focused renewed
      attention on their precursor phospholipids' location, structure, form and
      function. The nuclear matrix contains and supports dynamic pools of
      phosphatidylcholine and phosphatidylinositol which serve as parent molecules of
      lipid second messengers but also of other phospholipids requiring cyclical
      replacement as cells proliferate. Applications of new, highly sensitive and
      specific analytical methodologies based on tandem electrospray ionisation mass
      spectrometry and the use of stable isotopes have allowed both static and dynamic
      lipidomic profiling of these endonuclear phospholipid pools. Together with more
      conventional enzymatic analyses and evaluation of the effect of specific "knock
      out" of phospholipid transfer capacity, a number of important principles have
      been established. Specifically, a compartmental capacity to synthesise and
      remodel highly saturated phosphatidylcholine exists alongside transport
      mechanisms that facilitate the nuclear import of phosphatidylinositol and other
      phospholipids synthesised elsewhere within the cell. Subnuclear fractionation and
      the use of newly emerging techniques for sensitive lipidomic profiling of
      polyphosphoinositides, diacylglycerols and phosphatidate molecular species offer
      the potential for further significant advances in the near future.

PMID- 16581291
TI  - Protective effect of ebselen on cytotoxicity induced by cholestane-3 beta, 5
      alpha, 6 beta-triol in ECV-304 cells.
AB  - The protective effect of ebselen, with documented glutathione peroxidase-like
      activity and antioxidative and anti-inflammatory properties, on the cytotoxicity
      induced by oxysterol was investigated in ECV-304 cells with cholestane-3beta,
      5alpha, 6beta-triol (3-triol), one of the most toxic oxysterols. 3-triol
      exhibited significant cytotoxicity to ECV-304 cells in dose- and time-dependent
      manners. Pre-incubations with ebselen at different concentrations for 4 h
      effectively inhibited the decreases of the cell viability and the intracellular
      thiols level induced by 3-triol; suppressed the 3-triol-caused increases of the
      GPx and NOS activities, the LDH leakage and MDA formation. The inhibition of
      ebselen to the generation of intracellular ROS induced by 3-triol was monitored
      by luminol-, lucigenin-derived chemiluminescence and DCFH-DA-derived fluorescence
      assays. Our results suggest that ebselen inhibited 3-triol-induced enhancement of
      intracellular ROS level and the cytotoxicity of 3-triol is contributed to, for
      the most part, an enhanced formation of intracellular O2.-; nevertheless, the
      mitochondria were not the main source of intercellular O2.- contributed to the
      cytotoxicity of 3-triol. Ebselen lost its high protection against 3-triol-induced
      injuries in the presence of GSH probably due to the formation of the ebselen-GSH
      adduct. In conclusion, our investigations provide new utility for ebselen as a
      prospective antiatherosclerotic in both clinical and non-clinical situations.

PMID- 16581293
TI  - Reliability of a repeated-sprint test for field-hockey.
AB  - The purpose of this study was to assess the reliability of a repeated-sprint
      test, specifically designed for field-hockey, as it was based directly on the
      time-motion analysis of elite level competition. The test consisted of 6 x 30-m
      over-ground sprints departing on 25s, with an active recovery (approximately 3.1
      3.3 ms(-1)) between sprints. Ten highly trained, male, field-hockey players
      (mean+/-S.D.: age, 23+/-3 years; body mass, 78.1+/-7.1 kg) participated in this
      study. Following familiarisation, the subjects performed the repeated-sprint test
      on two occasions, 7 days apart. The reliability of the test variables was
      assessed by the typical error of measurement (TE). The total sprint time was very
      reliable (T(1): 26.79+/-0.76 s versus T2: 26.83+/-0.74 s), as the TE was 0.7%
      (95% CL, 0.5-1.2%). However, the percent sprint decrement was less reliable (T1:
      5.6+/-0.9% versus T2: 5.8+/-1.0%), with the TE being 14.9% (95% CL, 10.8-31.3%).
      In summary, it is suggested that this field-hockey-specific, repeated-sprint test
      is very reliable when the results are presented as the total sprint time.

PMID- 16581294
TI  - Pet ownership in immunocompromised children--a review of the literature and
      survey of existing guidelines.
AB  - Pet ownership has been associated with both emotional and physical health
      benefits. However, owning pets may also pose health risks to immunocompromised
      patients through zoonotic transmission of disease. Our initial impression was
      that there is a lack of any evidence base in information given by health care
      professionals regarding these risks. We therefore aimed to produce evidence-based
      guidelines addressing this issue. A Pubmed search was undertaken and a variety of
      literature on zoonoses reviewed. Existing guidelines were evaluated and a survey
      of all Paediatric Oncology Centres in the UK performed. There is a paucity of
      level 1 and 2 data addressing this issue and clearly more studies, particularly
      Randomised Controlled Trials (RCTs), are required. Nevertheless, general themes
      emerged and certain specific guidance was produced based on that produced by the
      Centres for Disease Control and Prevention in the US. Animal-associated pathogens
      of concern include Toxoplasma gondii, Cryptosporidium spp., Salmonella spp.,
      Campylobacter spp., Giardia lamblia, Rhodococcus equi, Bartonella spp.,
      Bordetella bronchiseptica, Chlamydia psittaci and dermatophytes. Despite this,
      the literature would suggest that with the exception of Bartonella henselae and
      dermatophytes only a relatively small number of infections in people are likely
      to be associated with pet contact. The majority of pet species do not appear to
      pose a major risk to immunocompromised children. Some animals, particularly
      reptiles, should be avoided because of the high risk of salmonellosis. Guidelines
      include general advice on good hygiene practices, veterinary care, pet foods,
      purchasing of new pets and age restrictions. Health care professionals should
      actively enquire about household pets and provide accurate information and
      practical advice on how to minimise the risk of infection. However, the overall
      benefits of the human-animal bond must be considered and with proper handling and
      husbandry immunocompromised patients should be able to continue to enjoy the
      significant benefits of pet ownership.

PMID- 16581296
TI  - X-linked lymphoproliferative syndrome: an X-cellent question.

PMID- 16581295
TI  - Angiotensin-converting enzyme 2 in lung diseases.
AB  - The renin-angiotensin system (RAS) plays a key role in maintaining blood pressure
      homeostasis, as well as fluid and salt balance. Angiotensin II, a key effector
      peptide of the system, causes vasoconstriction and exerts multiple biological
      functions. Angiotensin-converting enzyme (ACE) plays a central role in generating
      angiotensin II from angiotensin I, and capillary blood vessels in the lung are
      one of the major sites of ACE expression and angiotensin II production in the
      human body. The RAS has been implicated in the pathogenesis of pulmonary
      hypertension and pulmonary fibrosis, both commonly seen in chronic lung diseases
      such as chronic obstructive lung disease. Recent studies indicate that the RAS
      also plays a critical role in acute lung diseases, especially acute respiratory
      distress syndrome (ARDS). ACE2, a close homologue of ACE, functions as a negative
      regulator of the angiotensin system and was identified as a key receptor for SARS
      (severe acute respiratory syndrome) coronavirus infections. In the lung, ACE2
      protects against acute lung injury in several animal models of ARDS. Thus, the
      RAS appears to play a critical role in the pathogenesis of acute lung injury.
      Indeed, increasing ACE2 activity might be a novel approach for the treatment of
      acute lung failure in several diseases.

PMID- 16581297
TI  - The induction and maintenance of T cell anergy.
AB  - While the "true" role of T cell anergy in promoting peripheral tolerance
      continues to be debated, it is clear that studying the various models of anergy
      have led to important insight in terms of understanding the pathways and
      molecules responsible for T cell activation and inhibition. This review will
      examine our current understanding of CD4+ T cell anergy. In particular, it will
      focus on the signaling pathways responsible for both the induction and
      maintenance of anergy. Furthermore, it will examine how specifically targeting
      these pathways can be exploited clinically in terms of promoting tolerance in
      transplantation and autoimmunity and inhibiting tumor-induced tolerance in the
      case of tumor-immunotherapy.

PMID- 16581298
TI  - Bead-isolated human CD4+CD25+ T regulatory cells are anergic and significantly
      suppress proliferation of CD4+CD25- T responder cells.

PMID- 16581292
TI  - Vigilance, alertness, or sustained attention: physiological basis and
      measurement.
AB  - Vigilance is a term with varied definitions but the most common usage is
      sustained attention or tonic alertness. This usage of vigilance implies both the
      degree of arousal on the sleep-wake axis and the level of cognitive performance.
      There are many interacting neural and neurotransmitter systems that affect
      vigilance. Most studies of vigilance have relied on states where the sleep-wake
      state is altered, e.g. drowsiness, sleep-deprivation, and CNS-active drugs, but
      there are factors ranging from psychophysics to motivation that may impact
      vigilance. While EEG is the most commonly studied physiologic measure of
      vigilance, various measures of eye movement and of autonomic nervous system
      activity have also been used. This review paper discusses the underlying neural
      basis of vigilance and its assessment using physiologic tools. Since, assessment
      of vigilance requires assessment of cognitive function this aspect is also
      discussed.

PMID- 16581299
TI  - Recombinant Escherichia coli expressing invasin targets the Peyer's patches: the
      basis for a bacterial formulation for oral vaccination.
AB  - We have investigated the tropism of nonpathogenic recombinant invasive
      Escherichia coli in the gastrointestinal tract and the efficacy of this invasive
      E. coli as an oral vaccine for cancer immunotherapy. E. coli expressing invasin
      from Yersinia pseudotuberculosis selectively invade nonphagocytic cells in which
      beta(1)-integrin is expressed and accessible. Following internalization the E.
      coli are degraded in the phagosome. Coexpression of listeriolysin O (LLO)
      mediates release of the content of the bacteria into the cytosol of the invaded
      cell. In vitro and in vivo experiments demonstrated that gut epithelial cells
      failed to be invaded by invasive E. coli, due to a basolateral localization of
      beta(1)-integrin. By contrast, selective uptake of invasive bacteria from the
      intestinal lumen into Peyer's patches was observed ex vivo. Once in this
      structure, invasive E. coli colocalized with dendritic cells and possibly B
      cells. Oral administration of invasive E. coli coexpressing the model antigen
      ovalbumin and LLO from Listeria monocytogenes was able to elicit systemic
      protection against a lethal challenge of B16 tumor cells expressing ovalbumin.
      These data demonstrate the selectivity of invasin-mediated invasion to the
      Peyer's patches and indicate the potential of nonpathogenic, invasive E. coli as
      an oral vaccine with applications in immunotherapy.

PMID- 16581300
TI  - Phase I Trial of sequential administration of recombinant DNA and adenovirus
      expressing L523S protein in early stage non-small-cell lung cancer.
AB  - L523S is an immunogenic lung cancer antigen that has demonstrated preclinical
      safety when the gene is injected intramuscularly as an expressive plasmid
      (pVAX/L523S) and when delivered following incorporation into an E1B-deleted
      adenovirus (Ad/L523S). We performed a phase I clinical trial in 13 stage IB, IIA,
      and IIB non-small-cell lung cancer patients. pVAX/L523S (8 mg on days 0 and 14 in
      all cohorts) and Ad/L523S (1, 20, 400 x 10(9) vp on days 28 and 56, cohorts 1, 2,
      and 3, respectively) were administered to 3 patients in each of three cohorts. No
      significant toxic effect was identified. All but 1 patient demonstrated greater
      than or equal to twofold elevation in anti-adenovirus antibodies. One of 10
      evaluable patients demonstrated L523S-specific antibody by direct IgG ELISA. Two
      patients developed disease recurrence and all remain alive after a median of 290
      days follow-up. Results suggest a high level of safety but evidence of L523S
      directed immune activation was limited, suggesting a need for modification of
      dose, schedule, and site of vaccination (i.e., intradermal) with further clinical
      testing.

PMID- 16581301
TI  - Adeno-associated virus vector serotypes mediate sustained correction of bilirubin
      UDP glucuronosyltransferase deficiency in rats.
AB  - Crigler-Najjar (CN) patients have no bilirubin UDP glucuronosyltransferase
      (UGT1A1) activity and suffer brain damage because of bilirubin toxicity. Vectors
      based on adeno-associated virus (AAV) serotype 2 transduce liver cells with
      relatively low efficiency. Recently, AAV serotypes 1, 6, and 8 have been shown to
      be more efficient for liver cell transduction. We compared AAV serotypes 1, 2, 6,
      and 8 for correction of UGT1A1 deficiency in the Gunn rat model of CN disease.
      Adult Gunn rats were injected with CMV-UGT1A1 AAV vectors. Serum bilirubin was
      decreased over the first year by 64% for AAV1, 16% for AAV2, 25% for AAV6, and
      35% for AAV8. Antibodies to UGT1A1 were detected after injection of all AAV
      serotypes. An AAV1 UGT1A1 vector with the liver-specific albumin promoter
      corrected serum bilirubin levels but did not induce UGT1A1 antibodies. Two years
      after injection of AAV vectors all animals had large lipid deposits in the liver.
      These lipid deposits were not seen in age-matched control animals. AAV1 vectors
      are promising candidates for CN gene therapy because they can mediate a reduction
      in serum bilirubin levels in Gunn rats that would be therapeutic in humans.

PMID- 16581302
TI  - Cytoglobin overexpression protects against damage-induced fibrosis.
AB  - Cytoglobin (Cygb), a member of the hexacoordinate globin superfamily (hxHb), is
      expressed in fibroblasts from a broad range of tissues. The physiological
      functions of hxHb are still unclear, but biochemical studies reveal that they can
      scavenge toxic species, such as nitric oxide, peroxynitrite, and hydrogen
      peroxide. We demonstrate that the overexpression of Cygb in rat hepatic stellate
      cells, both in vitro and in vivo, protects against oxidative stress, inhibiting
      their differentiation into a myofibroblast-like phenotype. Accordingly, the
      overexpression of Cygb reduces extracellular matrix deposition in both toxic and
      cholestatic models of liver injury. The overexpression of Cygb also promotes
      recovery from previously initiated damage-induced fibrogenesis. By inhibiting
      free radical-induced activation of hepatic stellate cells, Cygb plays an
      important role in controlling tissue fibrosis. Therefore, the normal upregulation
      of Cygb during tissue injury has a homeostatic effect, inhibiting free radical
      induced fibroblast activation and tissue fibrosis.

PMID- 16581303
TI  - Gene therapy for diabetic cardiomyopathy: a new approach for a difficult problem.

PMID- 16581304
TI  - Hexokinase and glucose-6-phosphatase activity in woodchuck model of hepatitis
      virus-induced hepatocellular carcinoma.
AB  - 2-Deoxy-2-[(18)F]fluoro-D-glucose ([(18)F] FDG) is used for PET imaging of
      woodchuck (Marmota monax) model of hepatocellular carcinoma (HCC). The usefulness
      of FDG on this animal model needs to be validated according to the hypothesized
      mechanisms. In this study, two key enzymes involved in glucose or [(18)F] FDG
      metabolism, hexokinase (HK) and glucose-6-phophatase (G6Pase), were examined for
      their enzymatic activities in the woodchuck models of HCC, which has not been
      studied before. After dynamic PET scans, woodchuck liver tissue samples were
      harvested and the homogenate was centrifuged. The supernatant was used for HK
      activity assay and the microsomal pellet was used for G6Pase assay. HK and G6Pase
      activities were measured by means of colorimetric reactions via kinetic and end
      point assays, respectively. Total protein content was measured by the Bradford
      method and used to normalize all enzyme activities. HK and G6Pase activities in
      woodchuck HCC will be used to correlate with in vivo PET imaging data. The
      woodchuck model of HCC had significantly increased levels of HK in the livers
      compared to the age-matching healthy woodchuck (7.96 +/- 1.27 vs. 2.74 +/- 0.66
      mU/mg protein, P < 0.01) and significantly decreased levels of G6Pase compared to
      healthy woodchuck (40.35 +/- 19.28 vs. 237.01 +/- 17.32 mU/mg protein, P < 0.01),
      reflecting an increase in glycolysis. In addition, significant differences were
      found in HK and G6Pase activities between HCC liver region (HK: 7.96 +/- 1.27
      mU/mg protein; G6Pase: 40.35 +/- 19.28 mU/mg protein) and surrounding normal
      liver region (HK: 2.98 +/- 0.92 mU/mg protein; G6Pase: 140.87 +/- 30.62 mU/mg
      protein) in the same woodchuck model of HCC (P < 0.01). Our study demonstrated an
      increased HK activity and a decreased G6Pase activity in liver of the woodchuck
      models of HCC as compared to normal woodchuck liver.

PMID- 16581305
TI  - Response of catalase activity to Ag+, Cd2+, Cr6+, Cu2+ and Zn2+ in five tissues
      of freshwater fish Oreochromis niloticus.
AB  - Catalase (CAT, EC 1.11.1.6) is an important enzyme in antioxidant defense system
      protecting animals from oxidative stress. Freshwater fish Oreochromis niloticus
      were exposed for 96 h to different concentrations of Ag(+), Cd(2+), Cr(6+),
      Cu(2+) and Zn(2+), known to cause oxidative stress, and subsequently CAT
      activities in liver, kidney, gill, intestine and brain were measured. In vivo,
      CAT was stimulated by all metals except Ag(+) in the liver and the highest
      increase in CAT activity (183%) resulted from 1.0 mg Cd(2+)/L exposure, whereas
      0.5 mg Ag(+)/L exposure resulted in a sharp decrease (44%). In tilapia kidney,
      cadmium and zinc had no significant effects on CAT activity, whereas 0.1 mg
      Cr(6+)/L exposure caused a decrease (44%). Cadmium and zinc did not significantly
      affect the CAT activity in gill; however, 0.5 mg Ag(+)/L exposure caused an
      increase (66%) and 1.5 mg Cr(6+)/L exposure caused a decrease (97%) in CAT
      activity. All metals, except Cu(2+)(41% increase), caused significant decreases
      in CAT activity in the intestine. In brain, 1.0 mg Zn(2+)/L resulted in an
      increase in CAT activity (126%), while 1.5 mg Ag(+)/L exposure caused a 54%
      decrease. In vitro, all metals -- except Ag(+) and Cu(2+) in kidney --
      significantly inhibited the CAT activity in all tissues. Results emphasized that
      CAT may be considered as a sensitive bioindicator of the antioxidant defense
      system.

PMID- 16581306
TI  - The TNF-alpha G-308A polymorphism is associated with C-reactive protein levels:
      the HERITAGE Family Study.
AB  - OBJECTIVE: Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF
      alpha), stimulate the release of C-reactive protein (CRP). We investigated the
      association between the TNF-alpha G-308A polymorphism and plasma CRP levels.
      METHODS: Subjects were 456 White (225 men, 231 women) and 232 Black (83 men, 149
      women) healthy adults who underwent a 20-week standardized exercise program in
      the HERITAGE Family Study. The TNF-alpha gene promoter polymorphism was
      determined using PCR amplification followed by NcoI digestion. Plasma CRP was
      measured using a high-sensitivity assay. RESULTS: Genotype frequencies were in
      Hardy-Weinberg equilibrium. After adjustment for age, smoking, alcohol
      consumption, maximal oxygen uptake and, in women, hormone use, the AA homozygotes
      for the G-308A polymorphism had higher baseline CRP levels than other genotypes
      in White and Black men (P<0.001 and P = 0.044, respectively) and in Black women
      (P = 0.032). Body mass index partly explained these associations in Blacks. The
      exercise program results provided further evidence for an association with the
      polymorphism. Among those with high CRP at baseline (> or = 3.0 mg/L), regular
      exercise decreased CRP less in AA homozygotes than in other genotypes (P =
      0.043). CONCLUSION: The AA genotype of the TNF-alpha G-308A polymorphism is
      associated with higher plasma CRP levels and less favorable CRP response to
      regular exercise.

PMID- 16581307
TI  - Adherence to calcium/vitamin D and estrogen protocols among diverse older
      participants enrolled in a clinical trial.
AB  - PURPOSE: This study was intended to identify characteristics of those who adhere
      poorly to calcium/vitamin D and estrogen replacement protocols, and aimed to
      assess the effects of ethnicity, socio-economic status, and health status on
      medication adherence. METHODS: The adherence rates of 107 older white, African
      American and Hispanic participants of a clinical trial involving calcium/vitamin
      D and either estrogen replacement or placebo therapy were analyzed. Structural
      equation modeling was used to test the hypothesis that minority participants
      would have lower adherence rates than white participants, but only if they had
      lower household incomes and educational achievement, more osteoporosis risk
      factors, negative health assessments, and fewer somatic complaints than white
      participants. RESULTS: The average age of participants was 76 years. Minority
      participants and those with lower SES had lower adherence rates than white
      participants and those with higher SES. Plausible models that met goodness-of-fit
      criteria showed that the estrogen/placebo adherence rates were affected directly
      by being African American or Hispanic and the SF-36 mental health score, and
      indirectly by somatic complaints. History of fracture and household income
      directly predicted calcium/vitamin D adherence rates. CONCLUSION: Efforts to
      improve adherence to medical regimens should consider differences in adherence
      behaviors based on ethnicity, SES, and mental health.

PMID- 16581308
TI  - Central chemoreception 2005: a brief review.
AB  - This brief review will place recent findings on specific neurons and receptors
      identified as putative central chemoreceptors, namely glutamatergic and
      serotonergic neurons and purogenic receptors, into the context of our working
      hypothesis that central chemoreception is a distributed property.

PMID- 16581309
TI  - Major classes of sensory neurons to the urinary bladder.
AB  - A novel in vitro bladder preparation was used to examine effect of various
      stimuli (stretch, von Frey hair compression, stroking of receptive fields,
      applications of chemical stimuli to the mucosa) on electrophysiological
      recordings from guinea pig bladder afferents in vitro. Several functionally
      distinct classes of bladder sensory neurons were distinguished. These include
      stretch-sensitive afferents-muscle mechanoreceptors which behaved as "in-series
      tension receptors" and tension-mucosal mechanoreceptors, which could be activated
      by stretch, mucosal stroking with light von Frey hair (0.1-2 mN) and by
      hypertonic solutions (1 M mannitol and 490-850 mM NaCl) applied locally to their
      receptive fields in the mucosa. In addition, we have recorded stretch-insensitive
      afferents-mucosal mechanoreceptors and chemoreceptors. The non-selective P2X/P2Y
      purinoreceptor antagonist, PPADS (30 microM) did not affect stretch-induced
      firing by low threshold muscle mechanoreceptors but significantly inhibited
      alpha,beta-methylene ATP (30 microM)-induced contractions and associated afferent
      firing. Transduction by low threshold stretch-sensitive muscle mechanoreceptors
      does not appear to involve exocytotic synaptic transmission since it occurs in
      Ca2+-free (with 1 mM EDTA and 6 mM Mg2+) Krebs solution. The data suggest that
      the endogenous transmitter ATP is not involved in mechanotransduction by this
      specific class of low threshold muscle mechanoreceptors in the guinea pig
      bladder; rather they appear to transduce mechanical stimuli directly, possibly
      via stretch-activated ion channels. Mechanisms of activation of other classes of
      mechanoreceptors and chemoreceptors remain to be established.

PMID- 16581310
TI  - Differential expression of hoxa2a and hoxa2b genes during striped bass embryonic
      development.
AB  - Here, we report the cloning and expression analysis of two previously
      uncharacterized paralogs group 2 Hox genes, striped bass hoxa2a and hoxa2b, and
      the developmental regulatory gene egr2. We demonstrate that both Hox genes are
      expressed in the rhombomeres of the developing hindbrain and the pharyngeal
      arches albeit with different spatio-temporal distributions relative to one
      another. While both hoxa2a and hoxa2b share the r1/r2 anterior boundary of
      expression characteristic of the hoxa2 paralog genes of other species, hoxa2a
      gene expression extends throughout the hindbrain, whereas hoxa2b gene expression
      is restricted to the r2-r5 region. Egr2, which is used in this study as an early
      developmental marker of rhombomeres 3 and 5, is expressed in two distinct bands
      with a location and spacing typical for these two rhombomeres in other species.
      Within the pharyngeal arches, hoxa2a is expressed at higher levels in the second
      pharyngeal arch, while hoxa2b is more strongly expressed in the posterior arches.
      Further, hoxa2b expression within the arches becomes undetectable at 60hpf, while
      hoxa2a expression is maintained at least up until the beginning of
      chondrogenesis. Comparison of the striped bass HoxA cluster paralog group 2 (PG2)
      genes to their orthologs and trans-orthologs shows that the striped bass hoxa2a
      gene expression pattern is similar to the overall expression pattern described
      for the hoxa2 genes in the lobe-finned fish lineage and for the hoxa2b gene from
      zebrafish. It is notable that the pharyngeal arch expression pattern of the
      striped bass hoxa2a gene is more divergent from its sister paralog, hoxa2b, than
      from the zebrafish hoxa2b gene. Overall, our results suggest that differences in
      the Hox PG2 gene complement of striped bass and zebrafish affects both their
      rhombomeric and pharyngeal arch expression patterns and may account for the
      similarities in pharyngeal arch expression between striped bass hoxa2a and
      zebrafish hoxa2b.

PMID- 16581312
TI  - Pathogenesis of retinal ganglion cell death in Leber hereditary optic neuropathy
      (LHON): possible involvement of mitochondria, light and glutamate.

PMID- 16581311
TI  - Comparison of molecular markers for strain typing of Leishmania infantum.
AB  - The epidemiology of Leishmania infantum, the etiological agent of visceral
      leishmaniasis, is changing rapidly; hence powerful typing tools are required in
      order to monitor the parasite populations spreading and to adapt adequate control
      measures. We compared here the resolving power of four molecular methods at the
      zymodeme level: PCR-RFLP analysis of kDNA minicircles (kDNAPCR-RFLP) and antigen
      genes (cysteine proteinase b and major surface protease, cpb- and gp63PCR-RFLP),
      multilocus microsatellite typing (MLMT) and random amplification of polymorphic
      DNA (RAPD) were applied to samples of 25 L. infantum MON-1 strains obtained from
      different hosts (HIV+ patients, HIV- patients and dogs) coming from three Spanish
      foci: Madrid, Mallorca and Ibiza. While RAPD was not sufficiently resolving, the
      other three methods allowed genotyping within the zymodeme. KDNAPCR-RFLP and MLMT
      were the most discriminatory and appeared the most adequate for strain
      fingerprinting. In an eco-geographical context, cpbPCR-RFLP, MLMT and kDNAPCR
      RFLP were all informative: they showed here a similar picture, with the existence
      of cluster(s) of isolates from the islands and other one(s) of mixed composition
      (Madrid and the islands). None of the markers revealed an association with the
      host type or the clinical form. In general, there was a significant correlation
      between each pair of distances calculated from the cpb, microsatellite and kDNA
      data, respectively, but visual inspection of the trees revealed a better
      congruence between cpb and microsatellite trees. The methods used here are
      complementary and each adapted to answer specific epidemiological questions.
      Their choice should be the result of a compromise between the required resolving
      power, the genetic features of the respective markers and the technical aspects.

PMID- 16581313
TI  - Identification and sizing of GAA trinucleotide repeat expansion, investigation
      for D-loop variations and mitochondrial deletions in Iranian patients with
      Friedreich's ataxia.
AB  - Friedreich's Ataxia (FA) is the commonest genetic cause of ataxia and is
      associated with the expansion of a GAA repeat in intron 1 of the frataxin gene.
      Iron accumulation in the mitochondria of patients with FA would result in
      hypersensitivity to oxidative stress. Mitochondrial DNA (mtDNA) could be
      considered a candidate modifier factor for FA disease, since mitochondrial
      oxidative stress is thought to be involved in the pathogenesis of this disease.
      We studied 25 Iranian patients (16 females and 9 males) from 12 unrelated
      families. DNA from each patient was extracted and frequency and length of
      (GAA)(n) repeat was analyzed using a long-range polymerase chain reaction (PCR)
      test. Also we investigated impact of GAA size on neurological findings, age of
      onset and disease development. In order to identify polymorphic sites and genetic
      background, the sequence of two hypervariable regions (HVR-I and HVR-II) of mtDNA
      was obtained from FA patients harbouring GAA trinucletide expansions. Alignment
      was made with the revised cambridge reference sequence (rCRS) and any differences
      recorded as single base substitution (SBS), insertions and deletions. Homozygous
      GAA expansion was found in 21 (84%) of all cases. In four cases (16%), no
      expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases
      with GAA expansions, ataxia, scoliosis and pes cavus, cardiac abnormalities and
      some neurological findings occurred more frequently than in our patients without
      GAA expansion. Molecular analysis was imperative for diagnosis of Friedreich's
      ataxia, not only for typical cases, but also for atypical ones. Diagnosis bases
      only on clinical findings is limited, however, it aids in better screening for
      suspected cases that should be tested. Our results showed that the rate of D-loop
      variations was higher in FA patients than control (P<0.05). mtDNA deletions were
      present in 76% of our patients representing mtDNA damage, which may be due to
      iron accumulation in mitochondria.

PMID- 16581314
TI  - Differences in animal housing facilities and diet may affect study outcomes-a
      plea for inclusion of such information in publications.

PMID- 16581315
TI  - Discontinuous ventilation in insects: protecting tissues from O2.
AB  - The "oxidative damage model" of proposes that the respiratory system of insects
      operates in manner that reduces and then regulates the partial pressure of oxygen
      around the tissues at a very low level. This is achieved through the actions of
      the discontinuous gas exchange cycle. Resting insects often exhibit a ventilatory
      cycle in which the spiracular valves severely limit gas exchange. The "oxidative
      damage model" argues that this pattern serves to minimize oxidative damage to the
      tissues. This interpretation is discussed in the context of a large literature
      describing oxidative damage in insects and other animals as normal a feature of
      organismal aging. Evidence is presented from a number of animal phyla
      demonstrating respiratory strategies designed to maintain similarly low partial
      pressures of oxygen at the tissue level.

PMID- 16581316
TI  - Development and validation of a rapid 96-well format based liquid-liquid
      extraction and liquid chromatography-tandem mass spectrometry analysis method for
      ondansetron in human plasma.
AB  - A rapid and sensitive LC-MS/MS method for the quantification of ondansetron was
      developed and validated. The plasma samples were treated by a semi-automated
      liquid-liquid extraction (LLE) in 1.2 mL 96-well format micro-tubes. Ondansetron
      and the internal standard (IS) granisetron were analyzed by combined reversed
      phase LC-MS/MS, with positive ion electrospray ionization, using multiple
      reactions monitoring (MRM). The statistical evaluation for this method reveals
      excellent linearity, accuracy and precision values for the range of
      concentrations 0.25-40.0 ng/mL. The proposed method enabled the reliable
      determination of ondansetron in bioequivalence studies after per os
      administration of a 4 or 8 mg tablet.

PMID- 16581318
TI  - Rapid quantitation of cyclophosphamide metabolites in plasma by liquid
      chromatography-mass spectrometry.
AB  - A method is described for the quantification of two metabolites of
      cyclophosphamide, specifically 4-hydroxycyclophosphamide (HCy), and
      carboxyethylphosphoramide mustard (CEPM). Plasma HCy is derivatized to the
      phenylhydrazone which is quantitated by LC-MS monitoring the chloride adduct of
      the derivative. The LLOQ based on material applied to the system is approximately
      20 fmol. Plasma CEPM concentration is determined using LC-MS with a deuterated
      internal standard. Both assays have 50-fold dynamic range and require less than
      4h to complete. The development of this rapid analytical method makes it feasible
      to adjust the dose of cyclophosphamide based on the pharmacokinetic disposition
      of HCy and CEPM in hopes of decreasing nonrelapse mortality in cancer patients.

PMID- 16581317
TI  - HPLC analysis of the second-generation antidepressant sertraline and its main
      metabolite N-desmethylsertraline in human plasma.
AB  - A liquid chromatographic method with ultraviolet detection was developed for the
      analysis of the recent antidepressant sertraline and its main metabolite N
      desmethylsertraline in human plasma. The analytes were separated on a C8 reversed
      phase column, using a mobile phase composed of acetonitrile and a 12.3 mM, pH 3.0
      phosphate buffer containing 0.1% triethylamine (35:65, v/v). Clomipramine was
      used as the Internal Standard. Using a solid phase extraction procedure with C2
      cartridges high extraction yields (>94%) and good purification from matrix
      interference were obtained. Good linearity was obtained in the 7.5-250.0 ng mL(
      1) range for sertraline and in the 10-500 ng mL(-1) range for N
      desmethylsertraline. The analytical method was validated in terms of precision,
      extraction yield and accuracy. These assays gave R.S.D.% values for precision
      always lower than 3.9% and mean accuracy higher than 90%. Thanks to its good
      selectivity, the method proved to be suitable for the analysis of plasma samples
      from patients treated with sertraline as either monotherapy or polypharmacy.

PMID- 16581319
TI  - Altered protein profile in chronic myeloid leukemia chronic phase identified by a
      comparative proteomic study.
AB  - Chronic myeloid leukemia is a hematological disorder in which the Ph chromosome
      is a marker of the disease, detected virtually in all cases. The chimeric
      transcripts encode a 210-kDa chimeric protein with altered tyrosine kinase
      activity, responsible for the disease phenotype. In this work, we tried to
      identify which are the molecular changes common to chronic phase patients, those
      that represent the chronic phase molecular phenotype. To address this problem we
      analyzed through a comparative proteomic approach, several CML bone marrow cells
      protein profile from patients in chronic phase and healthy bone marrow donors.
      From these results, we identified 31 differentially expressed proteins. Among
      these proteins, we pointed out c-Myc binding protein 1, 53BP1, Mdm4, OSBP-related
      protein 3 and Mortalin as putative candidates to BCR-ABL targets in chronic
      phase. Moreover, we describe for the first time the cytoplasmic protein map from
      bone marrow cells that helped in the elucidation of the changes we were looking
      for.

PMID- 16581320
TI  - Temperature dependence of chaperone-like activity and oligomeric state of alphaB
      crystallin.
AB  - The chaperone-like activity and the oligomeric state of alphaB-crystallin were
      studied at different temperatures and in the presence of urea and thiocyanate.
      The activity, assessed measuring the ability of alphaB-crystallin to prevent the
      aggregation of denatured insulin, strongly depends on temperature. While a
      significant activity increase was detected at 42 degrees C, the presence of urea
      and thiocyanate does not affect the protein activity in an irreversible way. In
      solution SAXS measurements performed in the same experimental conditions showed
      that alphaB-crystallin forms near-spherical, hollowed, polydisperse oligomers,
      whose dimensions change above 42 degrees C. Moreover, in the presence of urea and
      thiocyanate, a global fit analysis confirms the high stability of alphaB
      crystallin assemblies in relationship with their variable quaternary structure.
      In particular, the changes in the inner radius as well as the thickness and
      dispersion of the protein shell, account for the preservation of the chaperone
      like activity.

PMID- 16581321
TI  - Inflammation, brain damage and visual dysfunction in preterm infants.
AB  - Antenatal intrauterine infection and the fetal inflammatory response appear to be
      important pathogenetic factors in preterm birth and subsequent neonatal disorders
      of the lung and brain. In this paper, we expand this concept to include visual
      dysfunction. Although present data tend to support our notion, we suggest that
      more experimental and epidemiological research is needed to elucidate mechanisms
      of infection/inflammation-induced damage to the eye and visual brain pathways of
      preterm infants.

PMID- 16581322
TI  - Transient precursor strategy in mineral formation of bone.
AB  - The strategy in biomineralization of initially depositing a less ordered mineral
      and then transforming it into a more crystalline mature phase is probably
      widespread among invertebrates. The report in this issue by N.J. Crane, V.
      Popescu, M.D. Morris, P. Steenhuis, M.A. Ignelzi, Raman spectroscopic evidence
      for octacalcium phosphate and other mineral species deposited during
      intramembraneous mineralization. Bone (In press), using micro-Raman spectroscopy
      to study early mineral deposits in mice calvaria, provides strong evidence that
      the transient precursor strategy also occurs in vertebrates.

PMID- 16581323
TI  - Effects of a prostaglandin EP4 agonist, ONO-4819, and risedronate on trabecular
      microstructure and bone strength in mature ovariectomized rats.
AB  - The effects of a prostaglandin EP4 agonist, ONO-4819, and risedronate, a
      representative anti-resorptive drug, on trabecular microarchitecture and
      biomechanical properties were investigated in mature estrogen-deficient rats; and
      effects which affected microstructural components that contributed to the
      improvement of bone strength were also determined. Thirty-three-week-old OVX rats
      were treated with various doses of ONO-4819, risedronate, or their combination
      for 11 weeks. Bone mineral density (BMD), trabecular microstructure, and
      biomechanical strength were determined at the proximal tibia by peripheral
      quantitative CT, micro CT, and finite element analysis, respectively. Bone
      histomorphometry was performed at the same site. The results of trabecular
      structure analysis indicated that whereas risedronate functioned mainly in
      maintaining trabecular connectivity, ONO-4819 converted the fragile rod-like
      trabeculae caused by estrogen deficiency to a plate-like structure. In addition,
      ONO-4819 is one of the few drugs that are capable of increasing trabecular
      thickness. When the 2 drugs were combined, the beneficial effects of each drug on
      the trabecular microarchitecture were maintained, resulting in their additive
      effects on bone strength. The results of bone histomorphometry suggest that ONO
      4819 caused an increase in the rate of bone formation by stimulating the
      differentiation/recruitment of osteoblasts as well as their mineralizing
      function. ONO-4819 did not stimulate bone resorption, but rather exerted an anti
      resorptive function within a certain dose range. ONO-4819 and risedronate
      increased BMD and improved trabecular structure and biomechanical strength in an
      additive and independent manner. Thus, EP4 agonist ONO-4819 in combination with
      risedronate may be an effective treatment for osteoporosis.

PMID- 16581325
TI  - Statin safety and drug interactions: clinical implications.
AB  - The risks of muscle adverse events related to use of the 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, increase
      significantly with the addition of interacting drugs to a patient's therapy. The
      mechanism for most statin drug interactions involves the cytochrome P-450 system,
      which provides an indication of which drugs may interact. However, it is
      difficult to predict the probability of a drug interaction in a given patient
      because there are individual differences in sensitivity to increased statin drug
      levels. Drug metabolism studies show simvastatin and lovastatin to be especially
      sensitive to the inhibiting effects of other drugs on the cytochrome P-450 3A4
      (CYP3A4) isoenzyme. Atorvastatin metabolism is less affected by inhibitors of
      this isoenzyme. Case reports, postmarketing surveillance, and clinical trial data
      demonstrate the clinical effect of CYP3A4 inhibitors on statins. Also, through
      possible inhibition of statin biliary excretion and glucuronidation, gemfibrozil
      given concomitantly with rosuvastatin, lovastatin, and simvastatin significantly
      increases the risk of myopathy and rhabdomyolysis, a potentially life-threatening
      consequence of statin drug interactions.

PMID- 16581326
TI  - Statins, cardiovascular disease, and drug safety.
AB  - Available for almost 2 decades, the 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors, or statins, have emerged at the forefront of preventive
      drugs for cardiovascular disease because of a substantial clinical trial database
      demonstrating that statins reduce the risk for coronary artery disease morbidity
      and death across a broad range of at-risk patient cohorts. Although generally
      well tolerated, statins may be associated with infrequent adverse events that
      warrant serious and frank discussion, including myopathy and rhabdomyolysis. In
      2005, the National Lipid Association (NLA), a multidisciplinary, nonprofit
      association of healthcare providers and researchers in the lipid field, convened
      a Safety Task Force to undertake an intensive, fair-minded evaluation of
      available data on the effects of statins on muscle, liver, kidneys, and the
      brain. In the end, physicians and patients must weigh the potential clinical
      benefits of statin treatment against the potential risks when deciding whether to
      initiate treatment.

PMID- 16581327
TI  - Statin safety: an appraisal from the adverse event reporting system.
AB  - The adverse event (AE) profiles of 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) reductase inhibitor (statin) agents are of great interest, in particular the
      most recently approved statin, rosuvastatin. The forwarding of reports of AEs has
      been shown to be influenced by several reporting biases, including secular trend,
      the new drug reporting effect, product withdrawals, and publicity. Comparative
      assessments that use AE reporting rates are difficult to interpret under these
      circumstances, because such effects can themselves lead to marked increases in AE
      reporting. Consequently, many comparative reporting rate analyses are best
      carried out in conjunction with other metrics that put reporting burden into
      context, such as report proportion. All-AE reporting rates showed a temporal
      profile that resembled those of other statins when marketing cycle and secular
      trend were taken into account. A before-and-after cerivastatin withdrawal
      comparison showed a substantial increase in the reporting of AEs of interest for
      the statin class overall. Report proportion analyses indicated that the burden of
      rosuvastatin-associated AEs was similar to that for other statin agents. Analyses
      of monthly reporting rates showed that the reporting of rosuvastatin-associated
      rhabdomyolysis and renal failure have increased following AE-specific mass media
      publicity. Postrosuvastatin AE reporting patterns were comparable to those seen
      with other statins and did not resemble cerivastatin.

PMID- 16581328
TI  - Statin safety: lessons from new drug applications for marketed statins.
AB  - Safety has become a central issue in the management of dyslipidemia with statins.
      A review of New Drug Applications (NDAs) and the US Food and Drug Administration
      (FDA) Web site was conducted for all 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) reductase inhibitors, or statins, with a major focus on cerivastatin and
      rosuvastatin. The findings provide insight into the incidence of adverse events
      for this class of drugs and support the significant benefits of statins relative
      to associated risks. These data delineate the nature of statin associated liver,
      muscle, and renal adverse events. Although transaminase levels increase in a dose
      related fashion with statins, a definitive correlation between statin therapy and
      hepatotoxicity is not supported by statin NDA data. Statin-induced myopathy is a
      relatively rare event (1 in 1,000) and rhabdomyolysis is even rarer (1 in
      10,000). The cerivastatin NDA, along with its supplementary NDA, was the first to
      demonstrate a clear statin dose-response relation with myopathy and a threshold
      effect above which myotoxicity increases significantly. Proteinuria was
      identified as a consequence of statin therapy with data from the rosuvastatin
      NDA, and subsequent analysis suggests a class effect that is dose related but
      transient. Studies in cell culture suggest the mechanism is a pharmacologic
      effect on the proximal renal tubule. The available evidence suggests no clear
      renal toxicity with currently approved statins, because no declines in renal
      function or glomerular filtration rate have been documented over time. Overall,
      currently marketed statins have a very favorable benefit-to-risk relation with
      respect to liver, muscle, and renal issues.

PMID- 16581329
TI  - Statin safety: a systematic review.
AB  - A systematic review of cohort studies, randomized trials, voluntary notifications
      to national regulatory authorities, and published case reports was undertaken to
      assess the incidence and characteristics of adverse effects in patients treated
      with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or
      statins. For statins other than cerivastatin, the incidence of rhabdomyolysis in
      2 cohort studies was 3.4 (1.6 to 6.5) per 100,000 person-years, an estimate
      supported by data from 20 randomized controlled trials. Case fatality was 10%.
      Incidence was about 10 times greater when gemfibrozil was used in combination
      with statins. Incidence was higher (4.2 per 100,000 person-years) with
      lovastatin, simvastatin, or atorvastatin (which are oxidized by cytochrome P450
      3A4 [CYP3A4], which is inhibited by many drugs) than pravastatin or fluvastatin
      (which are not oxidized by CYP3A4). In persons taking simvastatin, lovastatin, or
      atorvastatin, 60% of cases involved drugs known to inhibit CYP3A4 (especially
      erythromycin and azole antifungals), and 19% involved fibrates, principally
      gemfibrozil. The incidence of myopathy in patients treated with statins,
      estimated from cohort studies supported by randomized trials, was 11 per 100,000
      person-years. For liver disease, randomized trials reported fewer hepatobiliary
      disorders in patients allocated statins than in those allocated placebo. The
      notification rate of liver failure to regulatory authorities was about 1 per
      million person-years of statin use. Randomized trials show no excess of renal
      disease or proteinuria in statin-allocated participants, and the decline in
      glomerular filtration rate was smaller with statins than with placebo. Evidence
      from 4 cohort studies and case reports suggests that statins cause peripheral
      neuropathy, but the attributable risk is small (12 per 100,000 person-years). No
      change in cognitive function was found in randomized trials of statins in elderly
      patients.

PMID- 16581330
TI  - Statin safety: an overview and assessment of the data--2005.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or
      statin drugs, have been studied in numerous controlled human research trials
      involving hundreds of thousands of study participants. Statins have been
      prescribed for millions of patients. Based on this vast research and clinical
      experience, statins have been shown to improve lipid blood levels and reduce
      atherosclerotic coronary artery disease (CAD) risk, resulting in reduced CAD
      morbidity and mortality, and in several studies, reduced overall ("all-cause")
      mortality. From a safety perspective, both research trial evidence and clinical
      practice experience have demonstrated that statins are generally well tolerated.
      However, as with all pharmaceuticals, safety considerations exist with both
      monotherapy and combination statin therapy, mainly involving potential adverse
      effects on muscle, liver, kidney, and the nervous system. The evidence supporting
      statin-related potential adverse experiences on these organ systems is sometimes
      strong and based on clear clinical trial evidence (such as the increased risk of
      muscle enzyme elevation with higher statin doses). The evidence is at other times
      more speculative, being based on case reports and inconclusive clinical trial
      data (such as possible favorable or unfavorable effects of statins on cognition).
      Because the use of statins is so widespread, it is useful for the clinician to
      understand statin safety issues and the level of available evidence supporting
      the contention that various adverse effects are caused by statins. This review
      presents an assessment of statin safety based on an overview of the current
      statin safety data and their clinical implications.

PMID- 16581332
TI  - An assessment of statin safety by muscle experts.
AB  - The National Lipid Association's (NLA) Muscle Safety Expert Panel was charged
      with the duty of examining the definitions, causative factors, and management of
      statin myopathy. The Panel was asked to use its evidence-based findings to form
      recommendations in response to a series of specific questions posed by the Task
      Force. The panel was composed of a clinical cardiologist, an exercise
      physiologist and skeletal muscle expert, and an expert in preventive cardiology
      who also examined skeletal muscle complications of statin use.

PMID- 16581331
TI  - Statin safety: an assessment using an administrative claims database.
AB  - The large administrative databases of health plans contain information on drug
      related medical adverse events (AE) and constitute an increasingly powerful tool
      for the assessment of drug safety. We conducted a retrospective observational
      study using an administrative managed care claims database covering 9 million
      members from diverse regions of the United States. Patients aged >or=18 years who
      received >or=2 prescriptions for lipid-lowering drugs between July 1, 2000 and
      December 1, 2004 were included in the study. Hospitalizations with diagnosis
      codes (International Classification of Diseases, 9th Revision, Clinical
      Modification [ICD-9]) related to muscle, kidney, and liver were determined for
      patients exposed to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors (statins), fibrates, extended-release niacin, cholesterol absorption
      inhibitors, or statin combination therapy. A total of 473,343 patients
      contributed 490,988 person-years of monotherapy and 11,624 person-years of
      combination dyslipidemia therapy. Rates of hospitalization due to AEs in patients
      on monotherapy with currently available statins were similar, whereas the
      incidence of hospitalization for muscle disorders increased 6.7-fold with
      cerivastatin therapy. Patients who received a lipid-lowering medication with a
      concomitant cytochrome P450 3A4 (CYP3A4) inhibitor had a 6-fold increased rate of
      muscle disorders, including rhabdomyolysis. Hypertension was associated with a 5
      fold increase in both muscle and renal events, whereas patients with diabetes
      mellitus had a 2.5-fold increased risk of renal events. No hospitalized cases of
      the index AEs were observed in study subjects during the 6-month period before
      initiation of the lipid-lowering drug. Statin monotherapy as currently prescribed
      is generally well tolerated and safe.

PMID- 16581333
TI  - An assessment of statin safety by hepatologists.
AB  - The purpose of the Liver Expert Panel was to provide advice to the National Lipid
      Association's (NLA) Safety Task Force in response to specific questions
      concerning liver-associated risks of statin therapy. The panel was composed of
      academic hepatologists with clinical and research interests in nonalcoholic fatty
      liver disease, lipid metabolic disorders, and drug hepatotoxicity.

PMID- 16581334
TI  - An assessment of statin safety by nephrologists.
AB  - Recently, concerns regarding potential adverse effects of the statins on the
      kidney have been raised. The Kidney Expert Panel of the National Lipid
      Association's (NLA) Safety Task Force, made up of 3 nephrologists, was convened
      to review all of the currently available evidence pertinent to determining
      whether statins cause kidney injury, independent of the known, rare mechanisms of
      rhabdomyolysis and allergic, drug-induced, interstitial nephritis. The Panel
      reviewed published and unpublished evidence and found none that suggested that
      statins, when used in doses currently approved by the US Food and Drug
      Administration (FDA), cause kidney injury.

PMID- 16581335
TI  - An assessment of statin safety by neurologists.
AB  - The National Lipid Association's (NLA) Statin Safety Task Force charged the
      Neurology Expert Panel with the task of reviewing the scientific evidence related
      to adverse effects with statins and providing assessments and advice regarding
      the safety of statins. The evidence included key adverse reaction statin
      literature identified via a Medline search by the Task Force and Panel members
      and the commissioned reviews and research presented in this supplement. Panel
      members were asked to use this evidence to independently form explicit answers to
      a series of questions posed by the Task Force. Panelists were asked to grade the
      type of literature and the confidence they had in it in forming their answers
      using prescribed scales. Panelists were encouraged to seek the highest level of
      evidence available to answer their questions and to concentrate on literature
      involving humans. In addition, the Neurology Expert Panel was asked to propose
      recommendations to regulatory authorities, health professionals, patients,
      researchers, and the pharmaceutical industry to address statin safety issues.

PMID- 16581336
TI  - Final conclusions and recommendations of the National Lipid Association Statin
      Safety Assessment Task Force.
AB  - This article summarizes the final conclusions of the National Lipid Association
      (NLA) Statin Safety Task Force, based on a review and independent research of New
      Drug Application (NDA) information, US Food and Drug Administration (FDA) Adverse
      Event Reporting System (AERS) data, cohort and clinical trial results, and
      analysis of administrative claims database information and the assessment of its
      4 Expert Panels, which focused on issues of statin safety with regard to liver,
      muscle, renal, and neurologic systems. Practical guidance in the form of
      recommendations to health professionals who manage the coronary artery disease
      risk of patients with statin therapy is provided.

PMID- 16581337
TI  - Benefit versus risk in statin treatment.
AB  - The Statin Safety Assessment Conference of the National Lipid Association (NLA),
      reported in this supplement to The American Journal of Cardiology, provides a
      comprehensive evaluation of old and new experience on adverse events associated
      with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or
      statins. To place these in context, one can express both the risk of side effects
      and the benefits for cardiovascular disease in terms of events per person-year of
      statin treatment. The mortality risk from fatal rhabdomyolysis is approximately
      0.3 per 100,000 person-years, and the risks of nonfatal rhabdomyolysis and of
      putative statin-attributable peripheral neuropathy are approximately 3 and 12
      events, respectively, per 100,000 person-years. Reports of acute liver failure
      and acute or chronic kidney disease give lower rate estimates that, even when
      corrected for underreporting, are approximately equal to the background rates of
      these conditions in the general population, lending scant support for statin
      attributable etiology. In contrast, the benefit of statin use is to avert several
      hundred deaths and several hundred cases each of heart and brain infarction per
      100,000 person-years in appropriately treated high-risk patients. Although
      population estimates such as these are useful, they must be translated repeatedly
      to individual patient-provider encounters, where clinical skill and art must
      combine with scientific evidence. The continued publication of individual case
      reports and small randomized trials among groups of patients with potential side
      effects should be encouraged. Statins should not be used in situations where
      minimal benefit is expected, as safety data and risk-benefit analysis must be
      meshed with guidelines that help the clinician decide whom to treat and how
      aggressively to treat.

PMID- 16581338
TI  - Society of Biological Psychiatry 61st Annual Meeting, May 18-20, 2006, Toronto,
      Ontario, Canada. Abstracts.

PMID- 16581341
TI  - Disaster planning for unconventional acts of civilian terrorism.

PMID- 16581343
TI  - Herbs or natural substances as complementary therapies for chronic kidney
      disease: ideas for future studies.
AB  - Chronic kidney disease (CKD) is an increasingly common condition with limited
      treatment options that is placing a major financial and emotional burden on the
      community. The use of complementary and alternative medicines (CAMS) has
      increased many-fold over the past decade. Although several compelling studies
      show renal toxicities and an adverse outcome from use of some CAMS, there is also
      emerging evidence in the literature that some may be renoprotective. Many
      nephrologists are unaware of these potential therapeutic benefits in treating
      CKD, or they are reluctant to consider them in research trials for fear of
      adverse effects (including nephrotoxicity) or deleterious interaction with co
      prescribed, conventional medicines. The increased use of self-prescribed CAMS by
      their patients suggests that practitioners and researchers should keep abreast of
      the current information on these agents. A primary goal of this article was to
      review the available scientific evidence for the use of herbs or natural
      substances as a complementary treatment for patients with CKD. A further goal was
      to report the literature on herbs that have been reported to cause kidney
      failure.

PMID- 16581344
TI  - Impact of native VLDL on tissue factor pathway inhibitor in endothelial cells and
      interactions between TFPI and lipoprotein lipase.
AB  - Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor
      (TF)-induced blood coagulation. A positive association between very low density
      lipoproteins (VLDLs) and TFPI has been reported in vivo. In contrast, one in
      vitro study indicates that TFPI may enhance lipoprotein lipase (LPL) activity,
      thereby increasing triglyceride hydrolysis. The current study was conducted to
      investigate how native VLDL influenced the synthesis and release of TFPI in
      endothelial cells, and how TFPI affected the LPL-induced hydrolysis of VLDL in
      vitro and at the endothelial surface. A spontaneously transformed immortal
      endothelial cell line (ECV304) and primary coronary artery cells (CoEc) were
      used, and VLDL was isolated from healthy volunteers by density gradient
      ultracentrifugation. Sequential free fatty acid (FFA) measurements were used to
      evaluate the kinetics of the LPL-induced hydrolysis. The levels of TFPI mRNAs in
      the stimulated cells were determined by quantitative real-time reverse
      transcription-ploymerase chain reaction (qPCR) using the ABI PRISM 7700 Sequence
      Detection System. Stimulation of ECV304 cells for 24 hours with native VLDL (0
      100 microg/mL) caused a dose-dependent increase of TFPI in the medium (6.7-23.8
      ng/10(6) cells, P < 0.001), without affecting the cellular content of TFPI. The
      expression of TFPI mRNA was significantly upregulated after 10 minutes of
      stimulation with n-VLDL. Both recombinant TFPI (r-TFPI) and LPL showed a dose
      dependent binding to ECV 304 cells without saturation, and no competitive binding
      interactions between LPL and TFPI were observed at the endothelial surface. The
      addition of increasing concentrations of r-TFPI to ECV 304 cells, preincubated
      with LPL, did not affect the hydrolysis of VLDL triglycerides. The maximal
      reaction velocity (V(max)) of LPL-induced hydrolysis of n-VLDL was not affected
      by the addition of increasing concentrations of r-TFPI to the reaction mixture in
      vitro. The current experimental study indicates an upregulation of TFPI synthesis
      and release by VLDL. LPL-induced hydrolysis of VLDL in vitro was not influenced
      by TFPI neither in suspension nor at the endothelial surface.

PMID- 16581345
TI  - Correlation between serum prostate-specific antigen and alpha-1-antitrypsin in
      men without and with prostate cancer.
AB  - Prostate specific antigen (PSA) is frequently used for prostate cancer (PCa)
      screening, but serum levels are also increased by prostate inflammation.
      Elevations in serum levels of alpha1-antitrypsin (ATT), a marker of inflammation,
      in cancer patients are well documented. However, an association between PSA and
      ATT has never been investigated. The authors, therefore, measured serum acute
      phase proteins (APPs) ATT, alpha1-acid glycoprotein, C-reactive protein, and
      alpha1-antichymotrypsin in 174 men without and 34 with newly diagnosed untreated
      PCa (38-80 years old). As expected, men with PCa had higher mean PSA levels than
      those without PCa (P < 0.00001). Men with PCa and those without PCa but with PSA
      >2 ng/mL (n = 68) had significantly higher ATT concentrations than those without
      these conditions (n = 106) (mean +/- SEM g/L): 1.94+/-0.083, 1.92+/-0.066, 1.25+/
      0.043, respectively; p <0.005). Interestingly, African-American men without PCa
      (n=111) had higher ATT levels than Caucasian men (n=63) (1.565+/-0.045 g/l versus
      1.395+/-0.056 g/l; p <0.005); and differences persisted in men with PSA >2 ng/ml
      (2.094+/-0.07 g/l versus 1.593 for all0.095 g/l; p<0.0002). There were no
      differences among groups in the levels of other APP. ATT showed the strongest
      correlation with PSA (r = 0.346 to 0.395; p <0.001) than any other APP (r < or
      =0.245). Our data suggest that men with PCa have higher ATT levels than those
      without PCa; and African-American men without PCa have higher ATT levels than
      Caucasian men. The possible implications of elevated ATT levels in African
      American men on the risk of PCa are discussed.

PMID- 16581347
TI  - Long-term ethanol consumption and macrocytosis: diagnostic and pathogenic
      implications.
AB  - Although excessive alcohol consumption is known to elevate the mean cell volume
      (MCV) of erythrocytes, the relationships among the intensity of ethanol exposure,
      the generation of abnormal red blood cell indices, and the underlying pathogenic
      mechanisms have remained unclear. The authors examined 105 alcoholics with a wide
      range of ethanol consumption (40-500 g of ethanol/day), 62 moderate drinkers
      (mean consumption 1-40 g/day), and 24 abstainers, who underwent detailed
      interviews, measurements of blood cell counts, markers of liver status, and
      circulating antibodies against ethanol-derived protein modifications. Follow-up
      information was collected from healthy volunteers with detailed records on
      drinking habits. Data from the NORIP project for laboratory parameters in
      apparently healthy moderate drinkers or abstainers (n = 845) were used for
      reference interval comparisons. The highest MCV (P < 0.001) and mean cell
      hemoglobin (MCH) (P < 0.01) occurred in the alcoholics. However, the values in
      the moderate drinkers also responded to ethanol intake such that the upper normal
      limit for MCV based on the data from moderate drinkers was 98 fl, as compared
      with 96 fl from abstainers. Follow-up cases with carefully registered drinking
      habits showed parallel changes in MCV and ethanol intake. Anti-adduct IgA and IgM
      against acetaldehyde-induced protein modifications were elevated in 94% and 64%
      of patients with high MCV, respectively, the former being significantly less
      frequent in the alcoholics with normal MCV (63%) (P < 0.05). The data indicate
      dose-related responses in red blood indices upon chronic ethanol consumption,
      which may also be reflected in reference intervals for hematological parameters
      in health care. Generation of immune responses against acetaldehyde-modified
      erythrocyte proteins may be associated with the appearance of such abnormalities.

PMID- 16581346
TI  - Significant inhibition of TRAIL-mediated fibroblast-like synovial cell apoptosis
      by IFN-gamma through JAK/STAT pathway by translational regulation.
AB  - The pathway of interferon-gamma (IFN-gamma)-induced suppression in tumor necrosis
      factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis of fibroblast
      like synovial cells (FLS) was investigated. rTRAIL triggered FLS apoptosis in a
      type II cell death manner, whereas IFN-gamma pretreatment significantly inhibited
      TRAIL-mediated apoptosis. As disruption of mitochondrial transmembrane potential
      (DeltaPsim), Leu-Glu-His-Asp ase (IETD ase) activity, and the appearance of
      hypodiploid DNA + cells were markedly suppressed in IFN-gamma-treated FLS in
      response to TRAIL, IFN-gamma-induced suppression was supposed to achieve at
      upstream of caspase-8. IFN-gamma rapidly phosphorylated signal transducers and
      activators of transcription 1 (STAT1), STAT3, and STAT6 as well as ERK, whereas
      enhanced neither phosphorylation of Akt nor nuclear translocation of nuclear
      factor kappaB (NF-kappaB) p65. Janus kinase (JAK)-induced phosphorylation of
      STAT1/3/6, which acts at translational regulation, seemed to be crucial because
      chemical inhibition of JAK as well as cycloheximide (CHX) abolished both the
      phosphorylation of STAT1/3/6 and the IFN-gamma-induced inhibitory effect.
      Although ERK was phosphorylated through IFN-gamma, chemical inhibition of ERK by
      PD98059 did not abolish the IFN-gamma-induced inhibitory effect. The authors
      tried to determine the responsible molecules; however, expression of TRAIL
      receptors; pro-caspase-3/-8/-9; Fas-associated death domain protein (FADD); tumor
      necrosis factor receptor 1-associated death domain protein (TRADD); silencer of
      death domain (SODD); FLICE inhibitory protein (FLIP); and Bcl-2, Bcl-xL, and Bax
      in FLS was not modulated by IFN-gamma. Although the authors have not yet
      clarified the precise mechanism, these data suggest that IFN-gamma/JAK/STAT
      pathway, which is supposed to be activated in inflammatory rheumatoid arthritis
      (RA) synovial tissues, contributes to form apoptosis resistance phenotype of the
      cells in situ, leading to a marked increase in cellularity of synovial cells.

PMID- 16581348
TI  - Correlation of perioperative platelet function and coagulation tests with
      bleeding after cardiopulmonary bypass surgery.
AB  - The authors evaluated the correlation of post-cardiopulmonary bypass surgery
      bleeding, measured as 24-hour chest tube output/kilogram body weight, with
      platelet function tests using glass bead adhesion and Thrombelastograph Platelet
      Mapping (Haemoscope Corporation, Niles, Ill); coagulation tests; patient
      characteristics; surgery parameters; and visual assessment of surgical field
      bleeding before closure as not bleeding (code 1), oozing (code 2), and excessive
      bleeding (code 3). All platelet function and coagulation tests indicated
      significant dysfunction 15 minutes after protamine neutralization of heparin.
      With the exception of glass bead adherence, these assays indicated poor recovery
      of function 1 hour postoperatively. By multiple regression, the most significant
      predictors of postoperative bleeding were a low body mass index (BMI) (P <
      0.0001), lowest core body temperature (P = 0.0006), and cross clamp time (P <
      0.0001). Low core temperature was significantly (P < 0.0001) correlated with
      cross clamp time, which the authors believe is the most likely cause of
      coagulation and platelet dysfunction. None of the platelet function tests
      significantly correlated with bleeding. Looking at the highest quartile of chest
      tube output patients (n = 19) versus the upper and lower 50th percentile of
      coagulation and platelet function, bleeding could be explained for 11 patients by
      BMI plus surgery parameters along with coagulation and/or platelet dysfunction.
      In three cases without negative surgery parameters, coagulation dysfunction was
      observed. The remaining five cases did not give a clear indication of which
      parameters were primarily responsible for the bleeding.

PMID- 16581349
TI  - Rudolf Virchow.

PMID- 16581351
TI  - A rose by any other name is still a rose.

PMID- 16581352
TI  - A pathologist's perspective of the somatoform disorders.
AB  - OBJECTIVE: The object of this study was to revisit the evidence that somatoform
      disorders should be classified as mental and not physical disorders, as viewed
      through the eyes of a pathologist rather than a psychiatrist. METHODS: An
      academic clinical pathologist was asked to review recent widening in the concepts
      of physical disease and to comment on whether these changes made the criteria for
      designating somatoform disorders as mental disorders more workable or less
      workable. RESULTS: The review showed that somatoform disorders share many
      characteristics with certain types of physical conditions, especially those with
      multiorgan manifestations and multifactor causes. The criteria used to separate
      somatoform disorders from physical diseases are now less clear than when this
      distinction was first proposed. CONCLUSION: Discussions for reviewing the status
      of the somatoform disorders for DSM-V need input from a wide range of medical
      disciplines besides psychiatry.

PMID- 16581353
TI  - Can DSM-V facilitate productive research into the somatoform disorders?
AB  - OBJECTIVE: To highlight key research issues relevant to the diagnostic
      classification of somatoform disorders and assess whether DSM-V can facilitate
      research. METHODS: A selective review of recent research findings in relation to
      the diagnostic categories of somatization disorder and hypochondriasis. RESULTS:
      The DSM-IV criteria have been ignored by researchers as they were either too
      restrictive or too broad to study the associated features of somatization and
      hypochondriasis. In view of the linear relationship between number of bodily
      symptoms and impairment, the appropriate cutoff point has yet to be established.
      Ongoing research highlights the perceptual and cognitive aspects of these
      disorders, which need to be researched further in order to improve management.
      CONCLUSION: DSM-IV did not facilitate research. Its successor should enable
      longitudinal studies to further elucidate the causes and perpetuating factors of
      somatization and illness worry rather than limit such studies by producing
      artificial criteria that may not be supported by subsequent research.

PMID- 16581354
TI  - Physical symptom disorder: a simpler diagnostic category for somatization
      spectrum conditions.
AB  - OBJECTIVE: To propose a simpler, more empiric, and patient-centered category for
      classifying physical symptoms that are "etiologically neutral," that is, not
      reliant on the assumption that symptoms that is poorly explained from a medical
      standpoint must de facto be psychological in origin. METHODS: Theoretical
      analysis, narrative review, and proposal. RESULTS: Studies have revealed several
      limitations in the current classification of somatoform disorders, including the
      poor reliability of lifetime symptom recall, the difficulty in adjudicating
      physical versus psychological explanations, and the stigma in assigning patients
      with medically unexplained symptoms to an Axis I psychiatric disorder. Physical
      symptom disorder (PSD) is proposed as a diagnostic category that would reside on
      Axis III (rather than Axis I) and replace somatization disorder, undifferentiated
      somatoform disorder, and pain disorder. PSD would consist of one or more physical
      symptoms currently present, not fully explainable by another medical or
      psychiatric disorder (with the exception of functional somatic syndromes),
      causing functional impairment. Duration must be at least 6 months, and severity
      could be graded as mild, moderate, or severe using a 15-symptom checklist (PHQ
      15). Finally, the type of symptoms or symptom syndromes present in the patient
      could be specified. CONCLUSIONS: PSD should be considered as a simpler and more
      inclusive diagnosis to replace several somatoform diagnoses currently in use.

PMID- 16581355
TI  - Somatoform disorders in DSM-IV: mental or physical disorders?
AB  - OBJECTIVE: To examine analytically the question of whether the characterization
      of somatoform disorders (SFDs) in Diagnostic and Statistical Manual, Fourth
      Edition (DSM-IV) provides adequate grounds for classifying them as mental
      disorders rather than as physical disorders. METHODS: Analytical examination.
      RESULTS: There are prima facie grounds for classifying SFDs as physical disorders
      since they are characterized by physical symptoms. The characterization of SFDs
      in DSM-IV does not provide adequate grounds for classifying them as mental
      disorders. CONCLUSION: The spectrum of SFDs is drawn too widely in DSM-IV. At
      least some of the conditions now listed as SFDs in DSM-IV should be either given
      a dual diagnosis or classified simply as physical disorders.

PMID- 16581356
TI  - Don't change a winning horse.

PMID- 16581357
TI  - Explaining medically unexplained symptoms: toward a multidimensional, theory
      based approach to somatization.
AB  - In spite of the apparent clinical importance of somatization, the concept does
      not have a single meaning. The focus of the present article is therefore not on
      scrutinizing existing diagnostic categories but rather on the different
      dimensions that relate to somatization and on the relevance of psychological
      models such as social learning theory, stress coping, illness cognition, and self
      regulation models for explaining more carefully the predisposing, precipitating,
      and perpetuating factors of (different types of) somatization. This combined
      approach could lead to the definition of more homogeneous and, therefore,
      clinically more meaningful subgroups of somatization.

PMID- 16581358
TI  - Bodily symptoms: new approaches to classification.
AB  - OBJECTIVE: To examine the current approach to classifying bodily symptoms in both
      psychiatry and medicine and to suggest better alternatives. METHODS: Theoretical
      analysis, narrative review, and theoretical proposal. RESULTS: The assumptions
      that (a) bodily pathology can always explain bodily symptoms, (b) psychopathology
      can always explain bodily symptoms in the absence of bodily pathology, and (c)
      dichotomizing bodily symptoms into "medical" and "psychiatric" types is
      clinically useful were all found to have questionable validity and utility.
      CONCLUSION: Alternative multiaxial diagnostic approaches for the classification
      of bodily symptoms are proposed. These are intended to (a) give greater
      prominence to bodily symptoms in their own right, (b) allow etiology to be
      conceptualized in terms of multiple factors, and (c) provide the basis for
      integrating medical and psychiatric approaches to patient care.

PMID- 16581359
TI  - Number of bodily symptoms predicts outcome more accurately than health anxiety in
      patients attending neurology, cardiology, and gastroenterology clinics.
AB  - BACKGROUND: In consecutive new outpatients, we aimed to assess whether
      somatization and health anxiety predicted health care use and quality of life 6
      months later in all patients or in those without demonstrable abnormalities.
      METHOD: On the first clinic visit, participants completed the Illness Perception
      Questionnaire (IPQ), the Health Anxiety Questionnaire (HAQ), and the Hospital
      Anxiety and Depression Scale (HADS). Outcome was assessed as: (a) the number of
      medical consultations over the subsequent 6 months, extracted from medical
      records, and (b) Short-Form Health Survey 36 (SF36) physical component score 6
      months after index clinic visit. RESULTS: A total of 295 patients were recruited
      (77% response rate), and medical consultation data were available for 275. The
      number of bodily symptoms was associated with both outcomes in linear fashion
      (P<.001), and this was independent of anxiety and depression. Similar
      associations were found in people with or without symptoms due to demonstrable
      structural abnormalities. Health anxiety was associated only with health-related
      quality of life in patients with symptoms explained by demonstrable
      abnormalities. CONCLUSION: The number of bodily symptoms and degree of health
      anxiety have different patterns of association with outcome, and these need to be
      considered in revising the diagnoses of somatization and hypochondriasis.

PMID- 16581360
TI  - Psychological assessment of patients with temporomandibular disorders:
      confirmatory analysis of the dimensional structure of the Brief Symptoms
      Inventory 18.
AB  - OBJECTIVE: This article analyzes the psychometric and structural properties of
      the Brief Symptoms Inventory 18 in a sample of patients with temporomandibular
      disorders (TMDs), given the convenience of a brief evaluation of distress in
      these patients. METHODS: Confirmatory factor analysis was carried out in a sample
      of 114 patients with TMDs. Two models were tested: the theoretical model with the
      original structure proposed--which considers three dimensions--and the empirical
      model obtained through the exploratory factor analysis initially carried out by
      Leonard R. Derogatis--which consists of the four-factor structure. RESULTS: Both
      models reached satisfactory indexes in confirmatory factor analysis. Empirical
      and theoretical reasons led us to prefer the original proposal of three
      dimensions: somatization, depression and anxiety, and general distress.
      CONCLUSION: The Brief Symptoms Inventory 18 has been demonstrated to be a
      reliable and valid tool for the assessment of distress in patients with TMDs,
      with the advantage of its simplicity and ease of application.

PMID- 16581361
TI  - Maternal serum screening and psychosocial attachment to pregnancy.
AB  - OBJECTIVE: The purpose of this study was to examine whether maternal serum
      screening (MSS) is associated with lower maternal attachment to pregnancy.
      METHODS: One hundred one pregnant women identified as at risk for fetal anomaly
      due to advanced maternal age completed a survey targeting their decisions
      regarding prenatal testing and their psychological attachment to their pregnancy.
      Of these women, 38 opted for no prenatal testing, 32 underwent MSS, and 31 had
      amniocentesis in their current pregnancy. RESULTS: The results indicate that,
      throughout their pregnancy, the women who underwent MSS reported lower bonding
      levels as compared with those who chose either amniocentesis or no testing
      procedures. CONCLUSION: The results suggest that MSS may disrupt the
      developmental trajectory of the maternal-fetal bond even after favorable results
      are known. This may be due in part to the fact that the probabilistic nature of
      MSS results creates feelings of confusion rather than reassurance for many women
      following receipt of favorable results.

PMID- 16581362
TI  - The effects of prior combat experience on the expression of somatic and affective
      symptoms in deploying soldiers.
AB  - OBJECTIVE: Deployment to a combat zone is undoubtedly an extremely stressful
      experience. It was hypothesized that, when faced with an impending wartime
      deployment, soldiers with prior combat experience would report minimal emotional
      problems accompanied by high rates of somatic complaints compared with combat
      naive soldiers. METHODS: Self-reports of posttraumatic stress disorder (PTSD) and
      affective and somatic complaints were collected from 2068 U.S. soldiers just
      prior to combat deployment during Operation Iraqi Freedom. RESULTS: Although the
      percentage of soldiers scoring positive for PTSD was nearly identical for the
      experienced and inexperienced groups, scores on the Affective and Somatic scales
      differed as a function of prior combat history. Previous combat experience was
      associated with lower affective and greater somatic complaints relative to combat
      naive soldiers. CONCLUSIONS: Consistent with theories of stress reaction,
      repression, and somatic amplification, combat-experienced soldiers reported
      limited affective complaints but greater somatic complaints relative to soldiers
      without combat experience.

PMID- 16581363
TI  - The relationship between sensory and sympathetic nervous system changes and
      posttraumatic stress reaction following whiplash injury--a prospective study.
AB  - OBJECTIVE: To investigate differences in sensory and sympathetic nervous system
      (SNS) function between whiplash-injured persons with and without a posttraumatic
      stress reaction (PTSR). To explore associations between sensory, SNS function,
      and persistent PTSR at 6 months postinjury. METHODS: Seventy-six acutely (<1
      month) whiplash-injured persons (10 with PTSR persisting to 6 months postinjury,
      14 with early PTSR that resolved, and 52 with no PTSR) were prospectively
      investigated. RESULTS: Those with persistent PTSR showed sensory hypersensitivity
      and impaired peripheral vasoconstriction compared to those whose PTSR resolved
      and those without PTSR (P<.05). The early presence of sensory hypersensitivity
      was associated with PTSR at 6 months, but this relationship was mediated by pain
      and disability levels. Impaired vasoconstriction and higher pain and disability
      levels were associated with PTSR at 6 months. CONCLUSION: Sensory disturbances
      following whiplash injury are associated with persistent PTSR but may be mediated
      by levels of pain and disability.

PMID- 16581364
TI  - Patterns of presentations of dizziness in primary care--a cross-sectional cluster
      analysis study.
AB  - OBJECTIVES: Dizziness is a common symptom in adults in primary care. We explored
      in a sample of people recruited from general practice the existence of patterns
      of presentations, their characteristics, and clinical and health service
      predictors. METHOD: We assessed in a cross-sectional random sample of people
      registered at London general practices in the United Kingdom the following:
      subtypes of dizziness, effect on personal activity and physical function,
      relevant medical and drug history, level of anxiety or depression, treatments
      received, and information on whether help was sought from their general
      practitioners. RESULTS: Of 1820 subjects, 442 (24.3%) reported symptoms of
      dizziness. We identified three clinical presentations. Group 1 was a
      "nonspecific" presentation experienced by 113 (25.5%) people and characterized by
      true vertigo, presyncope, disequilibrium, and other types of dizziness with
      severe impact on all aspects of function. The other two groups were characterized
      by true vertigo and presyncope. In Group 2 [193 (43.7%)], these symptoms had some
      impact on personal and daily function, whereas in Group 3 [136 (30.7%)], there
      was no impact. Eighty-four percent of the people in Group 1 consulted their
      family practitioner on account of their symptoms, 61% did so in Group 2, and only
      38% in Group 3. On multinomial logistic regression analysis, current depression,
      unemployment, and use of prescribed medication were predictors of the Group 1
      compared with Group 2, whereas increasing anxiety and depression scores on the
      Hospital Anxiety and Depression Scale were predictors of the Group 2 compared
      with the Group 3. CONCLUSIONS: This is the first step in classifying dizziness
      from a symptomatic and functional point of view. Further research is required on
      the natural progression of these presentations and their relationship to each
      other.

PMID- 16581365
TI  - Prevalence of self-reported symptoms attributed to hypoglycaemia within a general
      female population of the UK.
AB  - OBJECTIVE: To investigate the prevalence of symptoms attributed to hypoglycaemia
      that are reported by a general female population of the UK. METHOD: A health and
      well-being questionnaire, including questions relating to symptoms of low blood
      'sugar', medical history and anthropometry, was administered by post to 2000
      randomly selected women (17-50 years) in Nottinghamshire. To avoid biasing
      responses, participants were not made aware of the specific focus of the study.
      RESULTS: One thousand one hundred and thirty-six women returned the questionnaire
      (56.8% response rate). After exclusions, 37.9% of respondents reported symptoms
      that they attributed to hypoglycaemia, with a median of four episodes reported
      per month. A significant variation in the reporting of symptoms was found across
      body mass index (BMI) categories, with the highest prevalence of symptomatic
      subjects being found at the lowest BMI range (P<.05). CONCLUSION: More than a
      third of women in the UK report experiencing symptoms that they attribute to
      hypoglycaemia. Body mass index appears to be related to the experiencing of
      symptoms.

PMID- 16581366
TI  - The role of psychosocial factors in peptic ulcer disease: beyond Helicobacter
      pylori and NSAIDs.
AB  - A variety of organic etiologies are associated with peptic ulcer disease, and the
      most relevant of these are infection with Helicobacter pylori and use of
      nonsteroidal anti-inflammatory drugs. Between 5% and 20% of patients with gastric
      or duodenal ulcer, however, lack an identifiable organic etiology. In these
      patients particularly and in all ulcer patients in general, psychosocial factors
      may play a significant role. At present, there is no definitive study proving a
      causal relationship between psychological stress and the development of ulcer
      disease. Studies to date suffer from significant methodological limitations and
      have not effectively addressed the poor correlation between ulcer craters and
      ulcer symptoms. A conservative application of available data would suggest that
      psychosocial factors play a significant role in symptom perception and reporting
      in patients with dyspeptic symptoms and may play a role in ulcer formation.

PMID- 16581367
TI  - Psychosocial responses to environmental incidents: a review and a proposed
      typology.
AB  - OBJECTIVE: The objective of this review was to propose a typology for
      understanding the diversity of psychosocial reactions to environmental incidents.
      METHODOLOGY: The first section provides an introduction and background to the
      topic; we then attempt to provide a typology of psychosocial responses to
      environmental incidents. RESULTS: Response to an environmental incident can be
      usefully considered in terms of the exposure, the response of the individual, the
      action of professionals, the response of the community, and the influence of the
      society in which the incident occurs. We reviewed each of these factors.
      CONCLUSIONS: By examining incidents in an ordered framework, we suggest that a
      more comprehensive understanding is possible. We also suggest some basic ways in
      which the psychosocial management of such difficult and diverse incidents could
      be improved.

PMID- 16581368
TI  - Anger suppression mediates the relationship between optimism and natural killer
      cell cytotoxicity in men treated for localized prostate cancer.
AB  - OBJECTIVE: This study evaluated relations among optimism, depression, anger
      suppression and natural killer cell cytotoxicity (NKCC) in 61 men treated for
      localized prostate cancer (PC). METHOD: All participants were assessed at a
      single time point where demographics, optimism, depression and anger suppression
      were measured. We also collected peripheral venous blood to assess NKCC. RESULTS:
      Results showed that greater optimism was associated with greater NKCC (beta=.27,
      P<.05), less depression (beta=-.63, P<.001) and less anger suppression (beta=
      .29, P<.05). Furthermore, less anger suppression (beta=-.35, P<.01) was
      associated with greater NKCC. In a hierarchical regression model controlling for
      depression and then anger suppression, the relationship between optimism and NKCC
      became nonsignificant [beta=.18, t(56)=1.51, P=.14], while anger suppression
      remained significantly correlated with NKCC [beta=-.29, t(56)=-2.40, P<.05].
      CONCLUSIONS: Results suggest that optimism is associated with NKCC and a greater
      ability to adaptively express anger. Furthermore, it appears that less anger
      suppression partially mediates the relationship between optimism and NKCC.

PMID- 16581370
TI  - New directions in the study of Peptide h-bonds and Peptide solvation.

PMID- 16581371
TI  - Potential functions for hydrogen bonds in protein structure prediction and
      design.
AB  - Hydrogen bonds are an important contributor to free energies of biological
      macromolecules and macromolecular complexes, and hence an accurate description of
      these interactions is important for progress in biomolecular modeling. A simple
      description of the hydrogen bond is based on an electrostatic dipole-dipole
      interaction involving hydrogen-donor and acceptor-acceptor base dipoles, but the
      physical nature of hydrogen bond formation is more complex. At the most
      fundamental level, hydrogen bonding is a quantum mechanical phenomenon with
      contributions from covalent effects, polarization, and charge transfer. Recent
      experiments and theoretical calculations suggest that both electrostatic and
      covalent components determine the properties of hydrogen bonds. Likely, the level
      of rigor required to describe hydrogen bonding will depend on the problem posed.
      Current approaches to modeling hydrogen bonds include knowledge-based
      descriptions based on surveys of hydrogen bond geometries in structural databases
      of proteins and small molecules, empirical molecular mechanics models, and
      quantum mechanics-based electronic structure calculations. Ab initio calculations
      of hydrogen bonding energies and geometries accurately reproduce energy
      landscapes obtained from the distributions of hydrogen bond geometries observed
      in protein structures. Orientation-dependent hydrogen bonding potentials were
      found to improve the quality of protein structure prediction and refinement,
      protein-protein docking, and protein design.

PMID- 16581372
TI  - Backbone-Backbone H-Bonds Make Context-Dependent Contributions to Protein Folding
      Kinetics and Thermodynamics: Lessons from Amide-to-Ester Mutations.
AB  - The contribution of backbone-backbone hydrogen bonds (H-bonds) to protein folding
      energetics has been controversial. This is due, at least in part, to the
      inability to perturb backbone-backbone H-bonds by traditional methods of protein
      mutagenesis. Recently, however, protein backbone mutagenesis has become possible
      with the development of chemical and biological methods to replace individual
      amides in the protein backbone with esters. Here, we review the use of amide-to
      ester mutation as a tool to evaluate the contribution of backbone-backbone H
      bonds to protein folding kinetics and thermodynamics.

PMID- 16581373
TI  - Modeling Polarization in Proteins and Protein-ligand Complexes: Methods and
      Preliminary Results.
AB  - This chapter discusses methods for modeling electronic polarization in proteins
      and protein-ligand complexes. Two different approaches are considered: explicit
      incorporation of polarization into a molecular mechanics force field and the use
      of mixed quantum mechanics/molecular mechanics methods to model polarization in a
      restricted region of the protein or protein-ligand complex. A brief description
      is provided of the computational methodology and parameterization protocols and
      then results from two preliminary studies are presented. The first study employs
      quantum mechanics/molecular mechanics (QM/MM) methods to improve the accuracy of
      protein-ligand docking; here, incorporation of polarization is shown to
      dramatically improve the robustness of the accuracy of structural prediction of
      the protein-ligand docking by enabling qualitative improvement in the selection
      of the correct hydrogen bonding patterns of the docked ligand. The second study
      discusses a 2-ns simulation of bovine pancreatic trypsin inhibitor (BPTI) in
      water using a variety of fixed charge and polarizable models for both the protein
      and the solvent, analyzing observed root mean square deviations (RMSD),
      intraprotein hydrogen bonding, and water structure and dynamics. All of these
      efforts are in a relatively early stage of development, the results are
      encouraging in that stable methods have been developed, and significant effects
      of polarization are seen and (in the case of the QM/MM-based docking)
      improvements have been validated as compared to experiment. With regard to
      accuracy and robustness of full simulations, a great deal more work needs to be
      done to quantitate and improve the present models.

PMID- 16581374
TI  - Hydrogen bonds in molecular mechanics force fields.
AB  - This chapter reviews formulation and parametrization of molecular mechanics force
      fields with special attention to technical and inherent problems. Most striking
      among the shortcomings is the inadequacy of the simple point charge description
      as a means to describe energy and forces of interactions between polar molecules
      and between polar groups in macromolecules, including hydrogen bonds. The current
      state of efforts to improve the description of polar interactions is discussed.

PMID- 16581375
TI  - Resonance Character of Hydrogen-bonding Interactions in Water and Other H-bonded
      Species.
AB  - Hydrogen bonding underlies the structure of water and all biochemical processes
      in aqueous medium. Analysis of modern ab initio wave functions in terms of
      natural bond orbitals (NBOs) strongly suggests the resonance-type "charge
      transfer" (CT) character of H-bonding, contrary to the widely held classical
      electrostatic viewpoint that underlies current molecular dynamics (MD) modeling
      technology. Quantum cluster equilibrium (QCE) theory provides an alternative ab
      initio-based picture of liquid water that predicts proton-ordered two-coordinate
      H-bonding patterns, dramatically different from the ice-like picture of
      electrostatics-based MD simulations. Recent X-ray absorption and Raman scattering
      experiments of Nilsson and co-workers confirm the microstructural two-coordinate
      picture of liquid water. We show how such cooperative "unsaturated" ring/chain
      topologies arise naturally from the fundamental resonance-CT nature of B:cdots,
      three dots, centeredHA hydrogen bonding, which is expressed in NBO language as
      n(B)-->sigma(AH)(*) intermolecular delocalization from a filled lone pair n(B) of
      the Lewis base (B:) into the proximal antibond sigma(AH)(*) of the Lewis acid
      (HA). Stabilizing n(O)-->sigma(OH)(*) orbital delocalization, equivalent to
      partial mixing of resonance structures H(2)O:cdots, three dots, centeredHOH
      H(3)O(+) cdots, three dots, centered(-):OH, is thereby seen to be the electronic
      origin of general enthalpic and entropic propensities that favor relatively small
      cyclic clusters such as water pentamers W(5c) in the QCE liquid phase. We also
      discuss the thermodynamically competitive three-coordinate clusters (e.g.,
      icosahedral water buckyballs, W(24)), which appear to play a role in hydrophobic
      solvation phenomena. We conclude with suggestions for incorporating resonance-CT
      aspects of H-bonding into empirical MD simulation potentials in a computationally
      tractable manner.

PMID- 16581376
TI  - How hydrogen bonds shape membrane protein structure.
AB  - The energetic cost of partitioning peptide bonds into membrane bilayers is
      prohibitive unless the peptide bonds participate in hydrogen bonds. However, even
      then there is a significant free energy penalty for dehydrating the peptide bonds
      that can only be overcome by favorable hydrophobic interactions. Membrane protein
      structure formation is thus dominated by hydrogen bonding interactions, which is
      the subject of this review.

PMID- 16581377
TI  - Peptide and protein folding and conformational equilibria: theoretical treatment
      of electrostatics and hydrogen bonding with implicit solvent models.
AB  - Since biomolecules exist in aqueous and membrane environments, the accurate
      modeling of solvation, and hydrogen bonding interactions in particular, is
      essential for the exploration of structure and function in theoretical and
      computational studies. In this chapter, we focus on alternatives to explicit
      solvent models and discuss recent advances in generalized Born (GB) implicit
      solvent theories. We present a brief review of the successes and shortcomings of
      the application of these theories to biomolecular problems that are strongly
      linked to backbone H-bonding and electrostatics. This discussion naturally leads
      us to explore existing areas for improvement in current GB theories and our
      approach towards addressing a number of the key issues that remain in the
      refinement of these models. Specifically, the critical importance of balancing
      solvation forces and intramolecular forces in GB models is illustrated by
      examining the influence of backbone hydrogen bond strength and backbone dihedral
      energetics on conformational equilibria of small peptids.

PMID- 16581378
TI  - Thermodynamics Of alpha-Helix Formation.
AB  - The alpha-helix was the first proposed and experimentally confirmed secondary
      structure. The elegant simplicity of the alpha-helical structure, stabilized by
      hydrogen bonding between the backbone carbonyl oxygen and the peptide amide four
      residues away, has captivated the scientific community. In proteins, alpha
      helices are also stabilized by the so-called capping interactions that occur at
      both the C- and the N-termini of the helix. This chapter provides a brief
      historical overview of the thermodynamic studies of the energetics of helix
      formation, and reviews recent progress in our understanding of the thermodynamics
      of helix formation.

PMID- 16581379
TI  - The importance of cooperative interactions and a solid-state paradigm to
      proteins: what Peptide chemists can learn from molecular crystals.
AB  - Proteins and peptides in solution or in vivo share properties with both liquids
      and solids. More often than not, they are studied using the liquid paradigm
      rather than that of a solid. Studies of molecular crystals illustrate how the use
      of a solid paradigm may change the way that we consider these important
      molecules. Cooperative interactions, particularly those involving H-bonding, play
      much more important roles in the solid than in the liquid paradigms, as molecular
      crystals clearly illustrate. Using the solid rather than the liquid paradigm for
      proteins and peptides includes these cooperative interactions while application
      of the liquid paradigm tends to ignore or minimize them. Use of the solid
      paradigm has important implications for basic principles that are often implied
      about peptide and protein chemistry, such as the importance of entropy in protein
      folding and the nature of the hydrophobic effect. Understanding the folded states
      of peptides and proteins (especially alpha-helices) often requires the solid
      paradigm, whereas understanding unfolded states does not. Both theoretical and
      experimental studies of the energetics of protein and peptide folding require
      comparison to a suitable standard. Our perspective on these energetics depends on
      the reasonable choice of reference. The use of multiple reference states,
      particularly that of component amino acids in the gas phase, is proposed.

PMID- 16581380
TI  - UK medical schools: undervalued and undermined.

PMID- 16581381
TI  - Southall's CNEP trial more than stands up to scrutiny.

PMID- 16581382
TI  - Trialists should tell participants results, but how?

PMID- 16581383
TI  - Donepezil for severe Alzheimer's disease.

PMID- 16581384
TI  - Are any of the criticisms of the CNEP trial true?

PMID- 16581385
TI  - CNEP needs to return.

PMID- 16581386
TI  - Southall and colleagues vindicated once more.

PMID- 16581387
TI  - CNEP and research governance.

PMID- 16581388
TI  - How specific are therapeutic monoclonal antibodies?

PMID- 16581390
TI  - Letters or lectures?

PMID- 16581389
TI  - Course of bipolar illness after history of childhood trauma.

PMID- 16581391
TI  - Cuttings.

PMID- 16581392
TI  - Victoria G Hale.

PMID- 16581393
TI  - The future of clinical pharmacology in the UK.

PMID- 16581394
TI  - Obesity and risk of myocardial infarction: the INTERHEART study.

PMID- 16581395
TI  - Obesity and risk of myocardial infarction: the INTERHEART study.

PMID- 16581396
TI  - Obesity and risk of myocardial infarction: the INTERHEART study.

PMID- 16581397
TI  - Obesity and risk of myocardial infarction: the INTERHEART study.

PMID- 16581398
TI  - Interleukin 2 treatment in HIV-1 infection.

PMID- 16581400
TI  - Interleukin 2 treatment in HIV-1 infection.

PMID- 16581401
TI  - Subsidising exercise in elderly people.

PMID- 16581402
TI  - Does cannabis use cause schizophrenia?

PMID- 16581403
TI  - Fruit and vegetable consumption and stroke.

PMID- 16581404
TI  - Donepezil in patients with severe Alzheimer's disease: double-blind, parallel
      group, placebo-controlled study.
AB  - BACKGROUND: The cholinesterase inhibitor donepezil is used to treat mild-to
      moderate Alzheimer's disease. Its efficacy in severe dementia has not been
      assessed and is controversial. Our aim was to ascertain the effectiveness of
      donepezil in patients with severe Alzheimer's disease, by focusing primarily on
      cognition and activities of daily living. METHODS: We did a 6-month, double
      blind, parallel-group, placebo-controlled study in 248 patients with severe
      Alzheimer's disease (mini mental state examination score 1-10) who were living in
      assisted care nursing homes ran by trained staff in Sweden. We assigned patients
      oral donepezil (5 mg per day for 30 days then up to 10 mg per day thereafter,
      n=128) or matched placebo (n=120). Our primary endpoints were change from
      baseline to month 6 in the severe impairment battery (SIB) and modified
      Alzheimer's Disease Cooperative Study activities of daily living inventory for
      severe Alzheimer's disease (ADCS-ADL-severe). We analysed outcomes for patients
      with data at baseline and at one or more other timepoints (modified intent-to
      treat population) with last observation carried forward used to replace missing
      data. FINDINGS: 95 patients assigned donepezil and 99 patients assigned placebo
      completed the study. Patients treated with donepezil improved more in SIB scores
      and declined less in ADCS-ADL-severe scores at 6 months after initiation of
      treatment compared with baseline than did controls (least squares [LS] mean
      difference, 5.7, 95% CI 1.5-9.8; p=0.008, and 1.7, 0.2-3.2; p=0.03,
      respectively). The incidence of adverse events was comparable between groups
      (donepezil 82% [n=105] vs placebo 76% [n=91]), with most being transient and mild
      or moderate in severity. More patients discontinued treatment because of adverse
      events in the donepezil group (n=20) than in the placebo group (n=8).
      INTERPRETATION: Donepezil improves cognition and preserves function in
      individuals with severe Alzheimer's disease who live in nursing homes.

PMID- 16581405
TI  - WHO analysis of causes of maternal death: a systematic review.
AB  - BACKGROUND: The reduction of maternal deaths is a key international development
      goal. Evidence-based health policies and programmes aiming to reduce maternal
      deaths need reliable and valid information. We undertook a systematic review to
      determine the distribution of causes of maternal deaths. METHODS: We selected
      datasets using prespecified criteria, and recorded dataset characteristics,
      methodological features, and causes of maternal deaths. All analyses were
      restricted to datasets representative of populations. We analysed joint causes of
      maternal deaths from datasets reporting at least four major causes (haemorrhage,
      hypertensive disorders, sepsis, abortion, obstructed labour, ectopic pregnancy,
      embolism). We examined datasets reporting individual causes of death to
      investigate the heterogeneity due to methodological features and geographical
      region and the contribution of haemorrhage, hypertensive disorders, abortion, and
      sepsis as causes of maternal death at the country level. FINDINGS: 34 datasets
      (35,197 maternal deaths) were included in the primary analysis. We recorded wide
      regional variation in the causes of maternal deaths. Haemorrhage was the leading
      cause of death in Africa (point estimate 33.9%, range 13.3-43.6; eight datasets,
      4508 deaths) and in Asia (30.8%, 5.9-48.5; 11,16 089). In Latin America and the
      Caribbean, hypertensive disorders were responsible for the most deaths (25.7%,
      7.9-52.4; ten, 11,777). Abortion deaths were the highest in Latin America and the
      Caribbean (12%), which can be as high as 30% of all deaths in some countries in
      this region. Deaths due to sepsis were higher in Africa (odds ratio 2.71), Asia
      (1.91), and Latin America and the Caribbean (2.06) than in developed countries.
      INTERPRETATION: Haemorrhage and hypertensive disorders are major contributors to
      maternal deaths in developing countries. These data should inform evidence-based
      reproductive health-care policies and programmes at regional and national levels.
      Capacity-strengthening efforts to improve the quality of burden-of-disease
      studies will further validate future estimates.

PMID- 16581407
TI  - Outcome after neonatal continuous negative-pressure ventilation: follow-up
      assessment.
AB  - BACKGROUND: A previous randomised trial of continuous negative extrathoracic
      pressure (CNEP) versus standard treatment for newborn infants with respiratory
      distress syndrome raised public concerns about mortality and neonatal morbidity.
      We studied the outcome in late childhood of children entered into the trial to
      establish whether there were long-term sequelae attributable to either mode of
      ventilation. METHODS: Outpatient assessment of neurological outcome, cognitive
      function, and disability was done by a paediatrician and a psychologist using
      standardised tests. 133 of 205 survivors from the original trial were assessed at
      9-15 years of age. Of the original pairs randomly assigned to each ventilation
      mode, the results from 65 complete pairs were available. The primary outcome was
      death or severe disability. FINDINGS: Primary outcome was equally distributed
      between groups (odds ratio for the CNEP group 1.0; 95% CI 0.41-2.41). In unpaired
      analysis there was no significant difference between treatment modalities (1.05;
      0.54-2.06). Full IQ did not differ significantly between the groups, but mean
      performance IQ was 6.8 points higher in the CNEP group than in the conventional
      treatment group (95% CI 1.5-12.1). Results of neuropsychological testing were
      consistent with this finding, with scores on language production and visuospatial
      skills being significantly higher in the CNEP group. INTERPRETATION: We saw no
      evidence of poorer long-term outcome after neonatal CNEP whether analysis was by
      original pairing or by unpaired comparisons, despite small differences in adverse
      neonatal outcomes. The experience of our study indicates that future studies of
      neonatal interventions with the potential to influence later morbidity should be
      designed with longer-term outcomes in mind.

PMID- 16581406
TI  - Risk of deep vein thrombosis and pulmonary embolism after acute infection in a
      community setting.
AB  - BACKGROUND: Acute infection increases the risk of arterial cardiovascular events,
      but effects on venous thromboembolic disease are less well established. Our aim
      was to investigate whether acute infections transiently increase the risk of
      venous thromboembolism. METHODS: We used the self-controlled case-series method
      to study the risk of first deep vein thrombosis (DVT) (n=7278) and first
      pulmonary embolism (PE) (n=3755) after acute respiratory and urinary tract
      infections. Data were obtained from records from general practices who had
      registered patients with the UK's Health Improvement Network database between
      1987 and 2004. FINDINGS: The risks of DVT and PE were significantly raised, and
      were highest in the first two weeks, after urinary tract infection. The incidence
      ratio for DVT was 2.10 (95% CI 1.56-2.82), and that for PE 2.11 (1.38-3.23). The
      risk gradually fell over the subsequent months, returning to the baseline value
      after 1 year. The risk of DVT was also higher after respiratory tract infection,
      but possible diagnostic misclassification precluded a reliable estimate of the
      risk of PE after respiratory infection. INTERPRETATION: Acute infections are
      associated with a transient increased risk of venous thromboembolic events in a
      community setting. Our results confirm that infection should be added to the list
      of precipitants for venous thromboembolism, and suggest a causal relation.

PMID- 16581408
TI  - Asymptomatic enterothorax.

PMID- 16581409
TI  - Adult epilepsy.
AB  - The epilepsies are one of the most common serious brain disorders, can occur at
      all ages, and have many possible presentations and causes. Although incidence in
      childhood has fallen over the past three decades in developed countries, this
      reduction is matched by an increase in elderly people. Monogenic Mendelian
      epilepsies are rare. A clinical syndrome often has multiple possible genetic
      causes, and conversely, different mutations in one gene can lead to various
      epileptic syndromes. Most common epilepsies, however, are probably complex traits
      with environmental effects acting on inherited susceptibility, mediated by common
      variation in particular genes. Diagnosis of epilepsy remains clinical, and
      neurophysiological investigations assist with diagnosis of the syndrome. Brain
      imaging is making great progress in identifying the structural and functional
      causes and consequences of the epilepsies. Current antiepileptic drugs suppress
      seizures without influencing the underlying tendency to generate seizures, and
      are effective in 60-70% of individuals. Pharmacogenetic studies hold the promise
      of being able to better individualise treatment for each patient, with maximum
      possibility of benefit and minimum risk of adverse effects. For people with
      refractory focal epilepsy, neurosurgical resection offers the possibility of a
      life-changing cure. Potential new treatments include precise prediction of
      seizures and focal therapy with drug delivery, neural stimulation, and biological
      grafts.

PMID- 16581410
TI  - Parenteral nutrition in adult inpatients with functioning gastrointestinal
      tracts: assessment of outcomes.
AB  - Malnutrition is a common comorbidity that places inpatients at risk of
      complications, infections, long length of stay, higher costs, and increased
      mortality. Thus, nutrition support has become an important therapeutic adjunctive
      to the care of these patients. For patients unable to feed themselves, nutrition
      can be delivered via the parenteral or enteral routes. The formulations used to
      deliver nutrients and the route of nutrient delivery, absorption, and processing
      differ substantially between parenteral and enteral nutrition. Over the past two
      decades, many randomised clinical trials have assessed the effects of parenteral
      versus enteral nutrition on outcomes (ie, complications, infections, length of
      stay, costs, mortality) in diverse inpatient populations. From a search of
      medical publications, studies were selected that assessed important clinical
      outcomes of parenteral versus enteral feeding or intravenous fluids in patients
      with trauma/burn injuries, surgery, cancer, pancreatic disease, inflammatory
      bowel disease, critical illness, liver failure, acute renal failure, and organ
      transplantation. Our goal was to determine the optimum route of feeding in these
      patient groups. The available evidence lends support to the use of enteral over
      parenteral feeding in inpatients with functioning gastrointestinal tracts.

PMID- 16581411
TI  - Robert Cory and the vaccine syphilis controversy: a forgotten hero?

PMID- 16581412
TI  - A souvenir from the Canary Islands.

PMID- 16581413
TI  - Genetic testing for age-related macular degeneration.

PMID- 16581414
TI  - Risk factors for treatment outcome in fungal keratitis.
AB  - PURPOSE: To identify risk factors at diagnosis that can serve as prognostic
      indicators of primary treatment failure in cases of fungal keratitis. DESIGN:
      Prospective, nonrandomized, interventional, comparative study. PARTICIPANTS: A
      total of 115 consecutive patients with fungal keratitis treated at one center
      during a 6-month period. METHODS: Patients with a microscopic corneal ulcer smear
      that was positive for fungus were enrolled and treated with 5% natamycin
      monotherapy according to the protocol of the hospital. Treatment responses were
      assessed at the end of 4 weeks. The prognostic indicators were used in a Poisson
      model for multiple regression analysis to estimate the relative risk of the main
      prognostic variables. MAIN OUTCOME MEASURES: Response of the ulcer to treatment.
      RESULTS: Of the 115 patients analyzed in the study, 52 (45.2%) were treatment
      successes, 27 (23.5%) had slow-healing ulcers, and 36 (31.3%) were refractory to
      primary treatment. Multivariate analysis showed that the predictors of treatment
      failure were ulcers that exceeded 14 mm(2) (P = 0.009), the presence of hypopyon
      (P = 0.003), and identification of Aspergillus (P = 0.003). CONCLUSION: In
      patients with fungal keratitis treated with 5% natamycin monotherapy, larger
      ulcer size and infection with Aspergillus were predictors of a poor outcome.

PMID- 16581415
TI  - Tandem scanning confocal corneal microscopy in the diagnosis of suspected
      acanthamoeba keratitis.
AB  - OBJECTIVE: To evaluate the role of in vivo corneal tandem scanning confocal
      microscopy (TSCM) in the definitive diagnosis of suspected Acanthamoeba keratitis
      (AK). DESIGN: Noncomparative interventional single-institution case series.
      METHOD: A retrospective case review of patients consecutively referred with
      suspected AK and undergoing corneal TSCM was performed. RESULTS: A total of 63
      cases that met the inclusion criteria for the study were referred for diagnostic
      evaluation. Tandem scanning confocal microscopy demonstrated Acanthamoeba
      cysts/trophozoites in 54 cases and fungal hyphae in 2, whereas 1 case was
      positive for both Acanthamoeba and fungus. Culture of the cornea or contact
      lenses was carried out in 35 cases, 9 of which were positive for Acanthamoeba.
      Six of the TSCM-positive cases also underwent corneal biopsy, being positive for
      Acanthamoeba in only 2. Six patients were negative for Acanthamoeba on TSCM, the
      etiology being fungal in 1 case, as shown by subsequent culture. One patient was
      positive on culture for Acanthamoeba but falsely negative by TSCM, which was
      limited by poor cooperation during the examination. Two cases initially
      masqueraded as Acanthamoeba keratitis but showed fungus on TSCM. Mean follow-up
      was 14 months. CONCLUSION: In vivo corneal TSCM can establish the diagnosis of
      Acanthamoeba keratitis rapidly and noninvasively, particularly when conventional
      microbiology is inconclusive.

PMID- 16581416
TI  - Impact of health education on active trachoma in hyperendemic rural communities
      in Ethiopia.
AB  - OBJECTIVE: Trachoma is one of the leading preventable causes of blindness
      worldwide. We evaluate the impact of a health education program on the prevalence
      of active trachoma in children 3 to 9 years old. DESIGN: Community randomized
      intervention study. Data were collected by means of cross-sectional surveys
      before and after intervention. PARTICIPANTS: Within 40 rural Ethiopian
      communities, households were selected at random, and all 3- to 9-year-old
      children within households were invited for examination. METHODS: Health
      education messages broadcast by radio were received by all communities.
      Nongovernmental organization activities to prevent trachoma, based on the SAFE
      (surgery for trichiasis, antibiotic treatment, face washing, and environmental
      improvements) strategy, were received by 30 of the 40 communities. Ten of these
      communities received enhanced educational messages using videos. Cluster summary
      measures were compared across surveys and intervention arms. Active trachoma at
      follow-up was modeled using random-effects logistic regression, adjusting for
      baseline prevalence and study area variability, at the cluster and individual
      level. MAIN OUTCOME MEASURES: Active trachoma in 3- to 9-year-old children and
      adult knowledge and behavior related to the nature and transmission of trachoma
      infection. RESULTS: At baseline, 1410 of 1960 (72%) children examined and, at
      follow-up, 1289 of 2008 (64%) had active trachoma. The overall reduction in
      prevalence at cluster level was 8% (95% confidence interval [CI], 4%-12%;
      P<0.001). There was a statistically significant increase in the awareness of
      trachoma. After adjustment for area and cluster level baseline prevalence, the
      odds of active trachoma were reduced in both intervention arms, standard (odds
      ratio [OR], 0.78; 95% CI, 0.53-1.16) and enhanced (OR, 0.76; 95% CI, 0.48-1.21),
      compared with the control arm, but not significantly. CONCLUSIONS: Overall, there
      was a small but statistically significant reduction in the prevalence of active
      trachoma between surveys, but differences between the 3 intervention arms were
      not statistically significant. Awareness of trachoma control increased in all
      communities, but there was little change in behavior associated with the
      transmission of Chlamydia trachomatis. It is therefore unlikely that observed
      reductions in active trachoma were solely due to health education.

PMID- 16581417
TI  - Patterns of rejection after deep lamellar keratoplasty.
AB  - PURPOSE: To describe 7 patients with keratoconus who underwent graft rejection
      after deep lamellar keratoplasty (DLK). DESIGN: Retrospective case series and
      literature review. PARTICIPANTS: Seven patients who underwent DLK for keratoconus
      between 1997 and 2001. These cases were compared with a previously reported case
      series of DLK for keratoconus between 1994 and 2001. METHODS: The clinical
      records of patients with rejection after DLK for keratoconus were examined to
      obtain details of the surgery, the interval to the rejection episode and its
      treatment, best-corrected visual acuity (BCVA), and presence of potential risk
      factors for rejection. The clinical features and course of rejection were
      compared with reports of corneal graft rejection in the literature. Patient
      characteristics were compared with the reported series of patients who had DLK
      for keratoconus. MAIN OUTCOME MEASURES: Final BCVA and number, type, and features
      of rejection episodes. RESULTS: The mean age was 28 years, with a median follow
      up of 40 months after DLK. Rejection occurred between 3 and 41 months
      postoperatively. Four patients were atopic, 4 had a penetrating keratoplasty in
      the fellow eye, and 1 had deep stromal vessels in the host cornea. Isolated
      epithelial rejection occurred in 1 patient and stromal rejection in 3 cases, and
      there were 3 cases of mixed stromal and epithelial rejection. Topical steroid
      therapy led to reversal of rejection in 5 cases. Two patients had progressive
      vascularization with graft failure and poor vision. The median final BCVA was 6/9
      (range, 6/6-6/36). CONCLUSIONS: Deep lamellar keratoplasty avoids the risk of
      endothelial rejection, but epithelial or stromal rejection may still occur.
      Recognition and appropriate treatment are needed to prevent graft failure with
      subsequent visual loss.

PMID- 16581418
TI  - Amniotic membrane transplantation with cauterization for keratoconus complicated
      by persistent hydrops in mentally retarded patients.
AB  - PURPOSE: Vigorous eye rubbing is a cause of extensive hydrops in mentally
      retarded patients with keratoconus. We describe a new management approach for
      this condition. DESIGN: Prospective, noncomparative, consecutive case series.
      PARTICIPANTS: Ten eyes of 10 mentally retarded patients aged 18 to 37 years (8
      with Down syndrome and 2 with oligophrenia not associated with Down syndrome).
      All patients had extensive and persistent hydrops in the course of keratoconus
      that was refractory to traditional therapy. INTERVENTION: The patients underwent
      multifocal cauterization of the cornea combined with amniotic membrane
      transplantation. MAIN OUTCOME MEASURES: Corneal protuberance, final corneal
      thickness, time to hydrops resolution, and postoperative complications were
      assessed. RESULTS: Hydrops was successfully resolved in all eyes. The mean
      initial corneal protuberance (7.6+/-4.2 mm) resolved after 21.4+/-9.5 days in all
      eyes. Mean final central corneal thickness was 0.47+/-0.11 mm. Extent of initial
      corneal protuberance, final corneal thickness, and time to resolution were
      positively correlated with each other. CONCLUSIONS: Amniotic membrane
      transplantation with cauterization in this series of mentally retarded patients
      was a highly effective treatment for persistent hydrops related to keratoconus.

PMID- 16581419
TI  - Prevalence and risk factors for cornea guttata in the Reykjavik Eye Study.
AB  - PURPOSE: To establish the age- and gender-specific prevalence of cornea guttata
      (CG) in citizens of Reykjavik, Iceland, 55 years and older. DESIGN: Cross
      sectional, random, population-based study. PARTICIPANTS: The 774 participants
      were those participating in the second examination of the Reykjavik Eye Study. At
      baseline, we had a response rate of 75.8%, and at the 5-year follow-up, 88% of
      the survivors participated. METHODS: We used slit-lamp and non-contact specular
      microscopy and endothelial specular photography as well as computer-assisted
      morphometry. We used a standardized grading system for CG. MAIN OUTCOME MEASURES:
      Diagnosis of primary central CG. RESULTS: The prevalence of CG is 11% for females
      and 7% for males both for right eyes and left eyes. Higher weight and higher body
      mass index are found to be associated with decreased risk of CG. Having smoked
      more than 20 pack-years increased the risk of CG more than 2-fold (P<0.02).
      CONCLUSIONS: Cornea guttata seem to be found more commonly in women than in men.
      Smoking for more than 20 pack-years increases the risk of developing CG more than
      2-fold.

PMID- 16581420
TI  - Prospective intrapatient comparison of 6.0-millimeter optic single-piece and 3
      piece hydrophobic acrylic foldable intraocular lenses.
AB  - PURPOSE: To compare postoperative performance and stability of 6.0-mm optic
      single- and 3-piece acrylic foldable intraocular lenses (IOLs). DESIGN:
      Prospective, randomized, self-controlled trial. PARTICIPANTS: Eighty eyes of 40
      patients with bilateral senile cataracts. INTERVENTION: Phacoemulsification and
      IOL implantation were performed. One eye of a patient was randomly assigned to
      the SA60AT single-piece IOL, and the contralateral eye was allocated to the
      MA60AC 3-piece IOL. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA),
      spherical equivalent, aqueous flare intensity, anterior chamber depth, amount of
      IOL decentration and tilt, area of anterior capsule opening, and degree of
      posterior capsule opacification (PCO) were measured 2 days, 1 week, and 1, 3, 6,
      and 12 months after surgery. Specular microscopy was performed at 12 months
      postoperatively. RESULTS: In the SA60AT group, the anterior chamber depth did not
      show significant changes after surgery (P>0.05; paired t test), and the
      refraction remained highly stable throughout the 1-year study period. The MA60AC
      group showed significant shallowing of the anterior chamber (P<0.05) and a myopic
      shift (P<0.05) up to 1 month after surgery. There were no significant differences
      between the 2 groups (P>0.05) in BCVA, aqueous flare intensity, the amount of IOL
      decentration, IOL tilt, area of anterior capsule opening, and degree of PCO
      throughout the 12-month follow-up period. CONCLUSIONS: Both the SA60AT single
      piece and MA60AC 3-piece lenses showed a minimum amount of decentration, tilt,
      anterior capsule contraction, and PCO. Although the MA60AC showed significant
      forward shift and myopic refractive changes after surgery, the SA60AT displayed
      little axial movement associated with highly stable refraction after surgery.
      This feature of the SA60AT should facilitate earlier spectacle prescription and
      quicker visual/social rehabilitation of patients after cataract surgery.

PMID- 16581421
TI  - New endoscopic technique to analyze various modern specialized intraocular lenses
      in research eyes and human eyes obtained postmortem.
AB  - PURPOSE: To describe a new modification of the Miyake-Apple posterior video
      photographic technique and its 2 variations. We have developed a new endoscopic
      technique that is especially amenable for observation of modern specialized
      intraocular lenses (IOLs). DESIGN: Laboratory study. PARTICIPANT: Three cadaver
      eyes obtained postmortem. METHODS: Human eyes obtained postmortem were prepared
      according to our modified preparation technique used for analyses of whole
      globes. An intraocular endoscope was utilized to demonstrate all aspects of the
      interior of an experimentally implanted IOL, with specialized reference to
      anterior segment structures, obtaining posterior, oblique, and side view images.
      MAIN OUTCOME MEASURES: Different interior dynamic views of the anterior segment
      structures before and after implantation of an IOL. RESULTS: High-magnification
      images of different intraocular structures both before and after device insertion
      as well as the device itself were obtained. Oblique and side view images from
      different locations were also available and informative. These images helped to
      create a 3-dimensional view of these objects and their relations to the
      surrounding structures. CONCLUSION: The combination of the intraocular endoscope
      with the closed-system technique is a useful addition to our 3 previously
      described techniques: (1) the original Miyake-Apple posterior video/photograph
      technique and the (2) closed system and (3) side/oblique view (keyhole technique)
      modifications.

PMID- 16581422
TI  - Prophylactic treatment of age-related macular degeneration report number 1: 810
      nanometer laser to eyes with drusen. Unilaterally eligible patients.
AB  - OBJECTIVE: To determine the effects of subthreshold 810-nm-diode laser treatment
      on the rate of development of choroidal neovascularization (primary end point)
      and the effect on visual acuity (VA) in participants with multiple large drusen
      in one eye and a preexisting neovascular age-related macular degeneration (AMD)
      lesion in the other. DESIGN: Multicenter, prospective, randomized controlled
      trial. PARTICIPANTS: Two hundred forty-four patients > or =50 years of age and
      with a neovascular or advanced AMD lesion in one eye and, in the fellow "study"
      eye, (1) at least 5 drusen > or = 63 mum in diameter, (2) Early Treatment
      Diabetic Retinopathy Study best-corrected VA (BCVA) of 20/63 or better, and (3)
      no evidence of neovascularization at baseline. METHODS: Patients were randomized
      to treatment or observation of their study eye at each of 22 centers. At each
      visit, the protocol specified that BCVA, a complete retinal examination, and
      fluorescein angiography be documented. Treated eyes had a grid of 48 extrafoveal,
      subthreshold diode (810 nm) laser spots, 125 mum in diameter, placed in an
      annulus outside of the foveola. Patients were seen at baseline and at 3, 6, 12,
      18, 24, 30, and 36 months after randomization. No retreatments were allowed. MAIN
      OUTCOME MEASURES: Development of choroidal neovascularization (as confirmed by
      fluorescein angiography) and change in BCVA. RESULTS: Throughout follow-up, the
      rate of choroidal neovascularization events in treated eyes consistently exceeded
      that in observed eyes. At 1 year, the difference was 15.8% versus 1.4% (P =
      0.05). Most of the intergroup differences in choroidal neovascularization events
      occurred during the first 2 years of follow-up. Treated eyes showed a higher rate
      of VA loss (> or =3 lines) at 3- and 6-month follow-ups relative to observed eyes
      (8.3% vs. 1% and 11.4% vs. 4%, respectively; Ps = 0.02, 0.07). After 6 months, no
      significant differences were observed in VA loss between groups. CONCLUSION:
      Prophylactic subthreshold 810-nm-diode laser treatment to an eye with multiple
      large drusen in a patient whose fellow eye has already suffered a neovascular
      event places the treated eye at higher risk of developing choroidal
      neovascularization. We advise against using prophylactic subthreshold diode laser
      treatment in these eyes.

PMID- 16581423
TI  - Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis)
      for neovascular age-related macular degeneration.
AB  - PURPOSE: To investigate whether multiple intravitreal doses of up to 2 mg of an
      antigen-binding fragment known as ranibizumab, derived from a humanized anti
      vascular endothelial growth factor antibody, can be tolerated and are
      biologically active when injected using a dose-escalating strategy in eyes of
      patients with neovascular age-related macular degeneration (AMD). DESIGN: Open
      label, 2-center, uncontrolled, randomized clinical study of 3 different dose
      escalating regimens of ranibizumab. PARTICIPANTS: Thirty-two patients with
      primary or recurrent subfoveal choroidal neovascularization secondary to AMD were
      enrolled. Baseline best-corrected visual acuity (VA) in the study eye was from
      20/40 to 20/640 (Snellen equivalent). METHODS: Treatment regimens consisted of 5,
      7, or 9 intravitreal injections of ranibizumab at 2- or 4-week intervals for 16
      weeks, with escalating doses ranging from 0.3 to 2.0 mg. Patients were evaluated
      through day 140, 4 weeks after their last injection. MAIN OUTCOME MEASURES:
      Safety was assessed based on ocular and nonocular adverse events, changes in VA,
      changes in intraocular pressure (IOP), slit-lamp ocular examination, changes in
      lesion characteristics based on fluorescein angiography and color fundus
      photography, and the presence of anti-ranibizumab antibodies. RESULTS: Twenty
      nine patients received an injection at baseline, and 27 patients completed the
      study through day 140. Results were similar across the 3 treatment groups. All
      patients experienced ocular adverse events, most of which were mild. The most
      common ocular adverse events were iridocyclitis (83%) and injection-site
      reactions (72%). Inflammation did not increase with repeated injections, despite
      the increasing ranibizumab doses. Transient mild IOP elevations were common after
      ranibizumab injection. No serum anti-ranibizumab antibodies were detected.
      Overall, median and mean VAs in the study eyes improved by day 140 in all 3
      groups. Only 3 of the 27 patients lost significant vision. There was no
      significant lesion growth, and a decrease in area of leakage from choroidal
      neovascularization was detected through day 140. CONCLUSIONS: Multiple
      intravitreal injections of ranibizumab at escalating doses ranging from 0.3 to
      2.0 mg were well tolerated and biologically active in eyes with neovascular AMD
      through 20 weeks. Mild transient ocular inflammation was the most common
      postinjection adverse event.

PMID- 16581425
TI  - Optical coherence tomography findings in stage 4A retinopathy of prematurity: a
      theory for visual variability.
AB  - PURPOSE: To report macular anatomic abnormalities in eyes with stage 4A
      retinopathy of prematurity (ROP) that may account for poor visual outcome despite
      an ophthalmoscopically normal-appearing posterior pole. DESIGN: Retrospective
      case series. PARTICIPANTS: Nine patients (14 eyes). METHODS: Nine patients (14
      eyes) diagnosed with stage 4A retinal detachments were imaged with optical
      coherence tomography (OCT) before repair by lens-sparing pars plana vitrectomy.
      One patient (2 eyes) 2 years after successful lens-sparing vitrectomy for stage
      4A detachment with reduced visual acuity underwent fluorescein angiography,
      fundus photography, and imaging with OCT. MAIN OUTCOME MEASURE: Optical coherence
      tomography findings. RESULTS: Preoperative OCT confirmed absence of macular
      involvement in 12 of 14 eyes. Two eyes demonstrated diffuse intraretinal
      posterior pole changes. Both eyes of a 2-year-old infant demonstrated a lack of
      normal foveal architecture on OCT scanning and an absent foveal avascular zone on
      angiography. CONCLUSIONS: Anatomic macular abnormalities--not immediately
      apparent ophthalmoscopically--may explain the variability in visual outcome after
      lens-sparing vitrectomy for stage 4A ROP.

PMID- 16581424
TI  - Risk factors for retinal detachment after cataract surgery: a case-control study.
AB  - PURPOSE: To determine risk factors for rhegmatogenous retinal detachment after
      cataract surgery. DESIGN: Retrospective case-control study. PARTICIPANTS AND
      CONTROLS: A consecutive series of 63298 cataract surgery procedures in 45520
      patients performed between August 1994 and March 2003 was identified. After
      exclusions for incomplete data, 249 cases of pseudophakic retinal detachment were
      matched with 845 controls that had cataract surgery on the same day, but without
      subsequent retinal detachment. METHODS: Details were extracted from the clinical
      records. A conditional logistic regression model for matched case-control groups
      was used. Multiple regression analysis was performed to estimate the odds ratio
      for each variable, with adjustment for the effects of other variables selected
      from the candidate pool. MAIN OUTCOME MEASURES: Occurrence of rhegmatogenous
      retinal detachment. RESULTS: The major risk factors (odds ratio [OR], 95%
      confidence interval [CI], P value) for detachment were posterior capsule tear
      (OR, 19.9; CI, 10.8-36.7; P<0.001), zonule dehiscence (OR, 12.4; CI, 3.8-41.2;
      P<0.001), retinal detachment in fellow eye (OR, 12.3; CI, 5.2-29.1; P<0.001),
      axial length >23 mm (OR, 3.2; CI, 2.0-5.0; P<0.001), and male gender (OR, 2.2;
      CI, 1.4-3.3; P<0.001). For patients aged >64 years, the odds ratio was linearly
      reduced for each subsequent decade. Differences in the surgical technique (i.e.,
      phacoemulsification vs. extracapsular extraction), type of anesthetic, prior
      glaucoma, or subsequent neodymium:yttrium-aluminum-garnet laser posterior
      capsulotomy were not significantly related to retinal detachment. Approximately
      37% (CI, 35%-38%) of retinal detachment was attributable to posterior capsule
      tear. CONCLUSIONS: Patient characteristics rather than surgical complications
      constitute the major risks factors for retinal detachment after cataract surgery.

PMID- 16581426
TI  - Photoreceptor loss overlying congenital hypertrophy of the retinal pigment
      epithelium by optical coherence tomography.
AB  - OBJECTIVE: To describe the cross-sectional retinal anatomy overlying congenital
      hypertrophy of the retinal pigment epithelium (CHRPE) using optical coherence
      tomography (OCT). DESIGN: Retrospective, observational, noncomparative case
      series. PARTICIPANTS: Ten consecutive patients with CHRPE. MAIN OUTCOME MEASURES:
      The main outcome measures were retinal and retinal pigment epithelium (RPE)
      thickness relative to normal tissue and the status of the retinal layers, in
      particular the photoreceptor layer. RESULTS: The median patient age was 36 years
      (mean, 34 years; range, 7-56 years). The CHRPE was within 6 mm of the optic disc
      or foveola in all patients. All patients showed retinal thinning and complete
      photoreceptor loss overlying the CHRPE. The sensory retina measured a mean of 68%
      of normal thickness (range, 47%-87%). Of the 8 patients with pigmented CHRPE, the
      CHRPE was 52% thicker than adjacent RPE. All 8 patients with pigmented CHRPE
      showed moderate relative shadowing of the underlying choroid. The 2 patients with
      nonpigmented CHRPE, presumed to represent large lacunae with thin CHRPE rim,
      showed absent RPE and increased transmission of light, not shadowing, into the
      choroid by OCT. Both patients with visual field testing showed a visual field
      defect corresponding to the photoreceptor loss. CONCLUSIONS: Using OCT, overlying
      retinal thinning and photoreceptor loss directly over CHRPE was found in 10
      consecutive patients. These findings likely account for related visual field
      loss.

PMID- 16581428
TI  - Outcomes associated with ganciclovir implants in patients with AIDS-related
      cytomegalovirus retinitis.
AB  - PURPOSE: To investigate complications associated with ganciclovir implants used
      to treat AIDS-related cytomegalovirus (CMV) retinitis, and to identify factors
      that predict poor outcomes. DESIGN: Retrospective chart review. PARTICIPANTS:
      Consecutive patients with AIDS-related CMV retinitis from 3 clinical facilities
      who underwent implantation procedures during the period January 1, 1995 through
      December 31, 2001. METHODS: Baseline for each patient was the date of the first
      implantation procedure performed during the study period by one of the
      facilities' surgeons (index implant). Medical and ophthalmological data were
      collected at baseline and at specific time points after baseline. The dates on
      which additional implantation procedures were performed and the dates on which
      complications or vision loss were identified were also recorded. Relationships
      between potential risk factors and outcomes were studied by Kaplan-Meier analyses
      and Cox proportional hazards regression models. MAIN OUTCOME MEASURES: Primary
      outcome measures included postoperative complications specifically related to or
      possibly related to ganciclovir implants. A secondary outcome measure was vision
      loss after implantation procedures. RESULTS: The charts of 174 patients (one
      study eye per patient; 279 implants) were reviewed. Median follow-up was 14.4
      months (range, 0-7 years). Complications specifically related to implants
      occurred throughout follow-up at a rate of 0.064 events per patient-year.
      Complications possibly related to implants occurred at an overall rate of 0.377
      per patient-year, but seemed to be more common during the first 2 years after
      baseline. During the first 2 years of follow-up, retinal detachments occurred at
      a rate of 0.156 events per patient-year. The cumulative risk of vision loss (> or
      =3 lines of Snellen visual acuity) at 7 years was 70%. Poor outcomes were
      associated with disease factors (size and activity of lesions), lack of highly
      active antiretroviral therapy (HAART), and lack of HAART-associated immune
      reconstitution, but not with surgical factors or implant-specific complications.
      CONCLUSIONS: Complications specifically associated with ganciclovir implants can
      occur many years after implantation procedures, but the incidence of such
      complications is low. Continued vision loss is not attributable directly to
      complications of implants in most cases. This information will help in planning
      of treatment strategies for CMV retinitis in long-term survivors of human
      immunodeficiency virus disease.

PMID- 16581427
TI  - Ultrahigh-resolution optical coherence tomography in patients with decreased
      visual acuity after retinal detachment repair.
AB  - OBJECTIVE: To assess microstructural changes in the retina that may explain
      incomplete visual recovery after anatomically successful repair of rhegmatogenous
      retinal detachments (RD) using ultrahigh-resolution optical coherence tomography
      (UHR OCT). DESIGN: Retrospective observational case series. PARTICIPANTS:
      Seventeen patients with decreased visual acuity after RD repair. Twelve patients
      had macula-involving and 5 had macula-sparing RDs. METHODS: The UHR OCT prototype
      capable of approximately 3 mum axial resolution was developed for clinical use.
      The UHR OCT images through the center of the fovea in 17 patients with visual
      complaints after RD surgery were obtained. Patients were either postoperative
      patients from the New England Eye Center or tertiary referrals. Baseline visual
      acuity, preoperative lens status, location of retinal detachment, macular
      involvement, and postoperative visual acuity were recorded. MAIN OUTCOME
      MEASURES: The UHR OCT images after RD repair. RESULTS: The UHR OCT images were
      obtained 1 to 84 months (median, 5 months) postoperatively. The mean preoperative
      logarithm of the minimum angle of resolution (logMAR) visual acuity was 1.37
      (Snellen equivalent, 20/390). The mean postoperative logMAR visual acuity was
      0.48 (Snellen equivalent, 20/60). Anatomical abnormalities that were detected
      included distortion of the photoreceptor inner/outer segments (IS/OS) junction in
      14 of 17 patients (82%), epiretinal membranes in 10 of 17 patients (59%),
      residual subretinal fluid in 3 of 17 patients (18%), and cystoid macular edema in
      2 of 17 patients (12%). Of the 5 patients with preoperative macula-on
      detachments, 4 had distortion of the outer retina after RD repair. CONCLUSIONS:
      The higher resolution of UHR OCT facilitates imaging of the IS/OS junction.
      Therefore, UHR OCT is able to confirm prior histopathologic findings that damage
      to photoreceptor outer segments may occur as a consequence of retinal detachment.
      This may explain poor postoperative visual acuity in eyes with anatomically
      successful repair.

PMID- 16581429
TI  - Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus
      retinitis.
AB  - OBJECTIVE: To evaluate the prevalence of and risk factors for immune recovery
      uveitis (IRU) in eyes of patients with AIDS and cytomegalovirus (CMV) retinitis.
      DESIGN: Enrollment data from a 19-clinical center cohort study. PARTICIPANTS:
      Three hundred seventy-four patients with AIDS and CMV retinitis affecting 539
      eyes. METHODS: Patients with AIDS were enrolled at 19 United States AIDS
      ophthalmology clinics. Data were collected by interview, review of medical
      records, ophthalmic examination, and phlebotomy. MAIN OUTCOME MEASURE: Immune
      recovery uveitis. RESULTS: Thirty-six patients (9.6%) were diagnosed with IRU
      involving 50 eyes. The CD4+ T-cell count of 31 of these had risen by > or =50
      cells per microliter above nadir to a level > or = 100 cells per microliter
      (immune recovery), making up 17.6% of the patients known to have immune recovery
      after diagnosis of CMV retinitis (95% confidence interval, 12.3%-24.1%). No
      patients with IRU were observed to have active retinitis or detectable CMV DNA in
      peripheral blood (P<0.001 and P<0.001 with respect to patients without IRU).
      Other factors associated with IRU were > or =25% retinal area (odds ratio [OR],
      2.72; P = 0.014) or posterior pole involvement with CMV retinitis (odds ratio,
      0.43; P = 0.039), treatment with intravitreous injection of cidofovir (OR, 10.6
      with respect to eyes never exposed to intravitreous or IV cidofovir; P<0.001),
      and male gender (OR, 0.26; P = 0.012). More eyes with IRU had visual acuity (VA)
      of 20/50 or worse (38.0% vs. 26.3%, P = 0.077) relative to eyes without IRU, but
      the proportions with VA of 20/200 or worse were similar (14.0% vs. 13.8%, P =
      0.96). Eyes with IRU more commonly had cystoid macular edema (CME) (45.5% vs.
      3.7%, P<0.001) and epiretinal membrane (48.9% vs. 13.3%, P<0.001) than eyes
      without IRU. CONCLUSIONS: Among eyes of patients with immune recovery, the
      prevalence of IRU is substantial. Eyes with IRU have a high risk of additional
      morbidity over and above that seen with CMV retinitis, with several-fold higher
      risk of CME and epiretinal membrane. Large CMV lesions and use of intravitreous
      cidofovir are risk factors for IRU.

PMID- 16581430
TI  - Polymorphisms within the tumor necrosis factor-alpha promoter region in patients
      with HLA-B27-associated uveitis: association with susceptibility and clinical
      manifestations.
AB  - PURPOSE: The existence of genetic variations in a number of cytokines has been
      considered to influence susceptibility or relate to disease severity in various
      autoimmune diseases. Among these, single-nucleotide polymorphisms (SNPs) of the
      tumor necrosis factor alpha (TNF-alpha) promoter at nucleotides -308 and -238 are
      considered to be protective against inflammation in HLA-B27-positive individuals,
      whereas the SNP at position -857 has been associated with disease development in
      anterior uveitis. We investigate a hypothesized association between the TNF-alpha
      -857 C-to-T, -308 G-to-A, and the TNF-alpha -238 G-to-A SNPs and the presence of
      HLA-B27-associated uveitis. DESIGN: Retrospective case-control study.
      PARTICIPANTS: One hundred fourteen Caucasian patients with HLA-B27-associated
      uveitis were studied. Mean age of patients was 44.9+/-14 years (range, 16-81),
      and mean duration of HLA-B27-associated uveitis was 115.6+/-104 months (range, 6
      months-51 years). Eighty-six patients (75.4%) suffered from an additional
      systemic manifestation of the disease. Sixty-three unrelated healthy HLA-B27
      positive blood donors and 88 unrelated healthy HLA-B27-negative individuals
      served as controls. METHODS: Genotypes were determined by polymerase chain
      reaction. MAIN OUTCOME PARAMETERS: Association of genotypes at positions -857, 
      308, and -238 of the TNF-alpha gene with disease development. RESULTS:
      Frequencies of the TNF-alpha -308GA and TNF-alpha -238GA genotypes were
      significantly lower in patients with HLA-B27-associated uveitis (6.1% and 0%,
      respectively) when compared with the HLA-B27-negative control group, 23% at -308
      (P = 0.003), and 7.9% at -238 (P = 0.0003). When compared with healthy HLA-B27
      positive controls, a significantly lower frequency of the TNF-alpha -238GA
      genotype was found among patients (6.3%, P = 0.015). The frequency of the TNF
      alpha -308GA genotype was also found to be lower in patients than among HLA-B27
      positive control subjects, without, however, reaching statistical significance
      (6.1%, P = 0.07). No difference in frequencies was seen among the different
      groups for the SNPs at position -857. CONCLUSION: Our data suggest that HLA-B27
      positive individuals show a higher susceptibility towards development of an
      intraocular inflammation in the presence of an A allele at nucleotide -238 and,
      to a lesser degree, at nucleotide -308 of the TNF-alpha gene promoter.

PMID- 16581431
TI  - Poststreptococcal syndrome uveitis: a descriptive case series and literature
      review.
AB  - PURPOSE: To describe the clinical features in a series of patients with
      poststreptococcal uveitis and to review literature on the pathophysiology and
      management. DESIGN: Retrospective and descriptive case series. PARTICIPANTS: Ten
      consecutive cases of poststreptococcal syndrome uveitis diagnosed between 1996
      and 2003. METHODS: Review of patient case notes. MAIN OUTCOME MEASURES: Age,
      laterality, clinical features, and anti-streptococcal lysin O titers. RESULTS:
      Ten consecutive cases of poststreptococcal syndrome uveitis were identified. All
      our cases had bilateral nongranulomatous inflammation and raised anti
      streptococcal lysin O titers. Collating data from previous reports and this
      series showed that 96% of the patients were below 40 years of age, and 87.5% had
      evidence of previous streptococcal infection. One third of the patients had
      posterior segment involvement. In our patients, this was in the form of vitritis,
      focal retinitis, optic disc swelling, and multifocal choroiditis. CONCLUSIONS:
      Poststreptococcal syndrome uveitis should be considered in the etiology of acute
      bilateral nongranulomatous uveitis in children and young patients.

PMID- 16581432
TI  - Capsule staining as an adjunct to cataract surgery: a report from the American
      Academy of Ophthalmology.
AB  - OBJECTIVE: This document evaluates currently available data in the published
      literature to answer the question of whether the use of dye such as indocyanine
      green or trypan blue to stain the lens capsule to improve visualization is safe
      and effective as an adjunct to cataract surgery. METHODS: Literature searches
      conducted in March 2003 and May 2004 retrieved 139 citations. The panel members
      reviewed the abstracts and selected 47 of possible clinical relevance for review.
      An additional 14 articles were identified for evaluation. Of the 61 articles
      reviewed, the panel members selected 36 for the panel methodologist to review and
      rate according to the strength of the evidence. A level I rating was assigned to
      properly conducted, well-designed, randomized clinical trials; a level II rating
      was assigned to well-designed cohort and case-control studies; and a level III
      rating was assigned to case series and case reports. RESULTS: There is level III
      evidence that indocyanine green, trypan blue, and fluorescein are each effective
      in staining the lens capsule and that indocyanine green and trypan blue provide
      better ease of use and visualization of the capsule than fluoroscein. There is
      level II evidence that staining the capsule is helpful in completing
      capsulorrhexis and that it is helpful for pediatric patients under age 5 years
      and in cases of white cataract. The overall surgical advantage of a completed
      continuous curvilinear capsulorrhexis using dye has not been demonstrated, but
      this may be related to the outcome measures chosen rather than a failure to
      confer advantage. There are substantial data indicating that trypan blue 0.1% is
      not toxic to the cornea. There are limited data suggesting that indocyanine green
      0.125% to 0.5% is not toxic to anterior segment structures. CONCLUSIONS: There
      are data confirming that dye is safe and effective as an adjunct for capsule
      visualization in cataract surgery. It is reasonable to use dye when inadequate
      capsule visualization may compromise the outcome in cataract surgery. More
      studies are needed to confirm a lack of toxicity of indocyanine green and trypan
      blue, particularly in the event of posterior segment or longer duration exposure.

PMID- 16581433
TI  - Vitrectomy for endophthalmitis.

PMID- 16581434
TI  - Meniscus level indicator of obstruction.

PMID- 16581435
TI  - Local anesthetic injections.

PMID- 16581436
TI  - Residents' perspective of OCEX.

PMID- 16581438
TI  - OCEX reliability.

PMID- 16581440
TI  - Thyroid orbitopathy.

PMID- 16581443
TI  - In this issue April 2006.

PMID- 16581441
TI  - Recognizing posterior microphthalmos.

PMID- 16581444
TI  - How cold light was introduced to arthroscopy.
AB  - In 1954, in a landmark publication, H. H. Hopkins reported that images could be
      transmitted through glass fibers. This stimulated many investigations and, in
      1957, B. Hirschowitz at the University of Michigan, succeeded in constructing a
      much-needed flexible gastroscope using optic glass fibers. Coating of the fibers
      by glass of lower refractive index was the next major step forward. Optical
      fibers were thus insulated and the accuracy of the transmitted image and the
      light transmission capacity of the fibers were enhanced. Working with American
      Cystoscope Makers Inc, L. Curtiss and H. Hett were the first to use glass fibers
      for illumination in an endoscope, producing a flexible ureteroscope in 1960. The
      light transmitted by the fibers was named "cold light" because it produced little
      heat, but the term had been used before for other types of illumination. The
      first arthroscope equipped with cold light was Watanabe's arthroscope No. 22
      built by Tsunekichi Fukuyo in 1967. However, Watanabe was not satisfied with the
      new instrument and he still preferred the conventionally illuminated No. 21
      arthroscope with the offset tungsten bulb at his tip. After R. W. Jackson
      reintroduced the technique to North America, most American pioneers used this
      conventionally illuminated arthroscope as well. But the early European
      arthroscopists had cold light instruments made by the German manufacturers R.
      Wolf and K. Storz since 1969. These rod-lens cold light instruments expanded in
      all markets during the following decade.

PMID- 16581445
TI  - Determination of factors influencing tissue effect of thermal chondroplasty: an
      ex vivo investigation.
AB  - PURPOSE: Scientific investigation of thermal chondroplasty using radiofrequency
      energy (RFE) is confounded by multiple factors associated with the technique. Our
      purpose was to determine the relative importance of the following factors on
      tissue effect (depth of tissue debridement plus depth of underlying cell death)
      of thermal chondroplasty: probe design, generator power setting, speed, force,
      and number of passes of the probe over treated tissue. We hypothesized the
      relative importance of these factors would be (from most to least important)
      power, passes, speed, force, and design. METHODS: Bovine patellae were treated
      using monopolar RFE. Sample size was based on a 2-level, half-factorial design.
      Low and high extremes of the factors tested were power setting (50 W v 110 W),
      passes (1 v 5), speed (3 mm/sec v 10 mm/sec), force (0.15 N v and 0.59 N), and
      probe design (electrode protrusion 25 microm v 125 microm). Samples were
      incubated with cell viability stain and examined using confocal laser microscopy
      to determine tissue effect. Data were analyzed using multiple regression.
      RESULTS: All factors that were tested significantly influenced tissue effect (P <
      .05). Power setting had the greatest effect, followed by design, speed, passes,
      and force. The following interactions of factors were also significant: design
      and force, power and passes. The optimal configuration resulting in least tissue
      effect was a power setting of 50 W, electrode protrusion of 25 microm, speed of
      10 mm/sec, 1 pass, and 0.15 N of applied force during treatment, which resulted
      in a predicted tissue effect of 99 +/- 15 microm. CONCLUSIONS: The least tissue
      effect of thermal chondroplasty was achieved with lower power using a probe with
      minimal electrode protrusion while performing a rapid, single, lower force pass
      of the probe over treated tissue. CLINICAL RELEVANCE: Power and probe design have
      the greatest influence among the factors tested; selecting these parameters
      preoperatively could control tissue effect.

PMID- 16581446
TI  - Cadaveric knee observation study for describing anatomic femoral tunnel placement
      for two-bundle anterior cruciate ligament reconstruction.
AB  - PURPOSE: The recently developed 2-bundle anterior cruciate ligament (ACL)
      reconstruction lacks sufficient anatomic background. The purpose of this anatomic
      study was to describe functional anteromedial (AM) and posterolateral (PL)
      portions of the natural ACL and to provide a reproducible description of the
      graft placement. Our hypothesis was that the core functional area of the femoral
      ACL attachment will be revealed by removing the surface fibrous membranous tissue
      of the ACL midsubstance and the attachment area. METHODS: The natural ACL was
      divided into 2 portions of AM and PL bundles in a flexion position; those bundles
      were most clearly defined when the knee was in flexion. The surface membrane of
      the ACL was removed and the margin was marked. The attachment site was removed
      after documenting its measurements. The knee position was corrected by digital
      photographs with the femoral bone in the correct lateral position. RESULTS: The
      length of the major axis of the AM and PL bundles averaged 9.2 +/- 0.7 mm and 6.0
      +/-0.8 mm, respectively. Both lengths of the minor axis of AM and PL bundles
      averaged 4.7 +/-0.6 mm. The distance from the attachment center of each AM and PL
      bundle to the posterior bone and articular surface border averaged 6.3 +/- 0.6 mm
      and 8.6 +/- 0.6 mm, respectively. The center of the AM and PL bundles was
      described as 1:40 and 3:10 clock positions, respectively, as left knee when the
      point was defined on the "lateral wall clock" of the intercondylar notch.
      CONCLUSIONS: The study described the position and area of each 2-bundle of AM and
      PL portions of the natural ACL by describing its central structure with the
      surface membrane removed. CLINICAL RELEVANCE: The detailed anatomic description
      of the natural ACL femoral attachment might suggest to surgeons where to make
      femoral tunnels during 2-bundle reconstruction.

PMID- 16581447
TI  - Analysis of meniscofemoral ligament tension during knee motion.
AB  - PURPOSE: The goal of this study was to show a functional role for the
      meniscofemoral ligaments (MFL) by analyzing MFL tension change through the full
      range of flexion and extension found at the human knee joint. METHODS: Ten fresh
      frozen human knees containing both the anterior and posterior MFLs (aMFL and
      pMFL) were studied. An analysis of ligament tension during passive motion was
      undertaken using an isometric transducer. RESULTS: The MFLs functioned in a
      nonisometric and reciprocal manner. The aMFL developed tension with flexion and
      the pMFL tension with extension. The aMFL tension increased with tibial external
      rotation compared with internal rotation. Combined MFL tension was greater in
      flexion (P < .001) and increased as the tibia was externally rotated (P = .008).
      CONCLUSIONS: The MFL tension changes identified through knee flexion and
      extension support the theory that the MFLs have a functional role in knee
      stability and protection. This warrants their consideration in the clinical
      management of meniscal and PCL injuries. CLINICAL RELEVANCE: This cadaver study
      of the lateral MFLs indicates that the anterior and posterior portions work in a
      reciprocal manner with flexion and extension and supports the fact that these
      ligaments have a functional role in the human knee joint.

PMID- 16581448
TI  - Cartilage healing after microfracture in osteoarthritic knees.
AB  - PURPOSE: To evaluate the clinical and radiologic results, second-look
      arthroscopic findings, histologic evaluation, and results of immunohistochemical
      staining and the Western blotting test for type II collagen after microfracture
      for full-thickness chondral defects in patients with osteoarthritic knee.
      METHODS: Between October 1997 and December 1998, 49 knees in 46 patients who had
      moderate osteoarthritic changes underwent microfracture; 44 patients (47 cases)
      had second-look arthroscopy and biopsy performed 1 year after surgery. The
      clinical outcomes were assessed by use of Baumgaertner's 9-point scale and joint
      space changes were measured radiographically; 18 knees underwent
      immunohistochemical study and 21 knees underwent Western blotting tests to
      identify formation of type II collagen. RESULTS: Significant improvements were
      noted for the parameters of daily living activity and pain (P < .05). The joint
      spaces were widened by 1.06 mm on standing anteroposterior and by 1.37 mm on
      standing lateral radiographs, which showed statistical significance (P < .05).
      Individual defects were filled with white tissue resembling cartilage on second
      look arthroscopy, and the cartilage healing was found by histologic evaluation.
      Type II collagen formation was identified qualitatively by immunohistochemical
      staining. Quantitative collagen formation by Western blotting showed 44% growth
      compared with the normal control. This healed tissue is a combination, or hybrid,
      of fibrocartilage and hyaline-like cartilage, and it is shown to contain type II
      collagen on immunohistochemical staining and the Western blotting test.
      CONCLUSIONS: Patients with full-thickness chondral defects in the osteoarthritic
      knee can have improved function and see an increase in joint space after
      microfracture. Cartilaginous tissue containing type II collagen is formed after
      the microfracture procedure in the osteoarthritic knee. LEVEL OF EVIDENCE: Level
      IV, retrospective case series.

PMID- 16581449
TI  - Infections following arthroscopic anterior cruciate ligament reconstruction.
AB  - PURPOSE: Infection after anterior cruciate ligament (ACL) reconstruction is a
      serious but uncommon complication. Optimal management has not been established.
      The purpose of our case series was to review our experience and published reports
      to identify risk factors, evaluate physical and laboratory findings, compare
      different treatments, and assess clinical outcomes. METHODS: Retrospective review
      of all the arthroscopic ACL reconstructions performed at our institution between
      1994 and 2002. Patients with intra-articular infections were evaluated and, when
      available, comparisons were made between patients with extra-articular infections
      and uncomplicated postoperative ACL reconstructions. RESULTS: Eleven
      postoperative infections were identified, all in patients who had hamstring
      autograft. Previous knee surgery, especially previous ACL reconstruction and
      tibial ACL graft fixation with a post and washer, was associated with increased
      infection. Laboratory data revealed elevated erythrocyte sedimentation rate
      (average, 67), C-reactive protein (average, 14), and intra-articular blood cell
      count (average, 52,000). All infections were eradicated with serial arthroscopic
      incision and drainage (average, 2.4 procedures) and intravenous antibiotics
      (duration, 14 to 42 days). The graft was retained in 10 of 11 patients. At an
      average follow-up of 22 months, the average Lysholm functional knee score was
      71.6 out of 100 points (range, 36-99). Of the 5 patients with fair/poor results,
      the most common chief complaint was pain and stiffness. CONCLUSIONS: Long-term
      goals for treatment of patients with postoperative ACL infections are to protect
      the articular cartilage and to maintain knee function. Timely initiation of
      treatment, including joint lavage, debridement, and antibiotics, are essential to
      treatment. Graft and hardware retention can successfully accomplish these long
      term goals. However, if early clinical response is not acceptable, strong
      consideration should be given to expedient graft and hardware removal. Excellent
      outcomes can be obtained, but results are usually lower than with uncomplicated
      cases. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 16581450
TI  - Meniscal debridement with an arthroscopic radiofrequency wand versus an
      arthroscopic shaver: comparative effects on menisci and underlying articular
      cartilage.
AB  - PURPOSE: Meniscal debridement with an arthroscopic radiofrequency (RF) wand
      versus an arthroscopic shaver and their comparative effects on menisci and
      underlying articular cartilage were studied. METHODS: When repair is not
      feasible, degenerative or post-traumatic meniscal tears often need debridement.
      Six fresh bovine knees were harvested, the tibial plateau was dissected free from
      the femoral articulation and placed in a saline bath at 28 degrees C, with 10% to
      15% of the posterior horn of menisci debrided arthroscopically, and the surfaces
      debrided using a basket punch plus shaver, punch plus RF wand, RF wand alone, and
      untreated control. Treatment time of each case was 24 seconds at wand power 7. We
      characterized an injury zone, as well as viability and metabolic activity of
      meniscal cells and tibial articular cartilage chondrocytes. RESULTS: Chondrocyte
      viability of the tibial articular surface was 96% to 98%. We saw no differences
      in viability or injury zone (0 to 150 microm) among debrided groups or versus the
      control for any experimental surface, with no significant difference in metabolic
      activity in menisci debrided surfaces versus control. Meniscal viability was
      variable with analyses showing substantial levels (150 to 500 microm) of cell
      death in debrided and control groups. Metabolic activity in treated meniscus was
      lower than in cartilage specimens. No significant differences were observed among
      treatment groups versus control. CONCLUSIONS: Focal areas of chondrocyte cell
      death were not seen. Meniscal samples showed cell death (150 to 500 mum)
      throughout the tissue. CLINICAL RELEVANCE: Debridement of menisci with a bipolar
      RF wand produces levels of cell injury and death similar to those of debridement
      with a basket punch mechanical shaver. The RF wand did not harm underlying
      articular surfaces and produced a precise cut to the meniscal surface.

PMID- 16581451
TI  - Effect of lesion location on fixation strength of the meniscal viper repair
      system: an in vitro study using porcine menisci.
AB  - PURPOSE: The Meniscal Viper Repair System (Arthrex, Naples, FL) is a novel suture
      based all-inside meniscal repair system. This study was performed to test whether
      the Meniscal Viper Repair System would provide superior fixation characteristics
      for vertical longitudinal meniscal lesions located closer to the periphery
      compared with those located further away from the periphery. METHODS: Vertical
      longitudinal lesions were created either 1 to 2 mm or 3 to 4 mm away from the
      periphery of porcine menisci. After repair with the Meniscal Viper Repair System,
      fixation characteristics were studied during cyclic (500 cycles, 5 to 50 N) and
      load to failure testing (5 mm/min) in a servo hydraulic device. RESULTS: Meniscal
      lesion repair location did not show significant differences in displacement or
      stiffness during cyclic testing. During load to failure testing, meniscal lesion
      repairs located 1 to 2 mm from the periphery showed superior load at failure
      (188.8 +/- 45.4 N) compared with repairs located 3 to 4 mm from the periphery
      (114.4 +/- 35.0 N) (P = .01). Stiffness and displacement during load to failure
      testing did not show statistically significant differences. CONCLUSIONS: The
      Meniscal Viper Repair System provides stronger meniscal repair strength when
      lesions are located within 1 to 2 mm of the periphery. CLINICAL RELEVANCE: The
      Meniscal Viper Repair System is better suited for repair of peripheral meniscal
      lesions located within 1 to 2 mm of the periphery. For lesions located in zone 2
      (within the central 50%), careful assessment of their distance from the periphery
      is recommended. For lesions located more than 3 to 4 mm away from the periphery,
      alternative repair systems or augmentation with other devices may be prudent.

PMID- 16581452
TI  - Midterm results of meniscal repair using the BioStinger meniscal repair device.
AB  - PURPOSE: The purpose of this study was to evaluate the midterm healing rate and
      any adverse events from meniscus repair using the BioStinger meniscus repair
      device (Linvatec, Largo, FL). METHODS: A retrospective review of a consecutive
      series of meniscal repairs performed by a single surgeon using the BioStinger was
      conducted. The BioStinger is cannulated, made of molded poly L-lactic acid, and
      inserted over a needle into the meniscus tissue. Clinical results and adverse
      events were noted, and Lysholm, Tegner, Cincinnati, and International Knee
      Documentation Committee (IKDC) activity scores were obtained on all patients.
      RESULTS: Forty-one patients underwent 41 meniscal repairs with an average follow
      up of 38.6 months (range, 24 to 69 months); 35 meniscus repairs were performed in
      conjunction with anterior cruciate ligament reconstruction and 6 in stable knees.
      Tears repaired were peripheral, posterior horn tears with an average length of 2
      cm. Clinical evidence of meniscal healing was observed in 95% at the time of last
      follow-up. Six second-look arthroscopies were performed and 2 failures were
      found. All other patients were symptom free. At follow-up, the mean Tegner score
      was 6.1 (2.8 preoperative), IKDC activity score was 3.3 (2.1 preoperative),
      Lysholm score was 90.6 (48.7 preoperative), and the mean Cincinnati score was
      86.7 (41.3 preoperative). Four patients had peripheral migration of the device
      without skin tenting or perforation; 3 underwent removal of the BioStinger from
      the soft tissues and the other resolved after 12 months. CONCLUSIONS: The midterm
      clinical success rate was 95% using the BioStinger device. Adverse events were
      observed in few cases. LEVEL OF EVIDENCE: Level IV, cases series.

PMID- 16581454
TI  - Primary stability of osteochondral grafts used in mosaicplasty.
AB  - PURPOSE: The goal of our experiments was to determine the primary stability of
      osteochondral grafts used in mosaicplasty. The effect of graft diameter and
      dilation, as well as multiple grafting, were studied in a porcine model. METHODS:
      Single osteochondral grafts, 4.5 and 6.5 mm in diameter, and multiple grafts were
      transplanted from the trochlea of porcine femurs to the weight-bearing area of
      the lateral femoral condyle. In the multiple grafting series, 3 grafts 4.5 mm in
      diameter were transplanted either in a row or in circular fashion. The grafts
      were first pushed in level with the surrounding cartilage surface, then they were
      pushed 3 mm below cartilage level. The push-in forces were measured. The effect
      of graft diameter and the extent of dilation on primary stability were studied as
      well as the influence of multiple grafting. RESULTS: In the case of 4.5-mm
      grafts, the mean level push-in force was 43.5 N, and pushing 3 mm below cartilage
      level required a mean of 92.5 N (n = 13). In the case of 6.5-mm grafts, level
      push-in required a mean of 76.2 N, and for pushing 3 mm below cartilage level a
      mean of 122.2 N force had to be used (n = 14). The length of the drill hole and
      the dilation were both 20 mm in each setting. When using 20-mm long drill holes
      and 15-mm dilation length, the values above were found to be 36.6 N and 122.5 N
      in the case of 4.5-mm grafts (n = 12). Mean level push-in force in the first
      (row) multiple series was 31.8 N, and pushing 3 mm below cartilage level required
      a mean of 52.17 N (n = 7). In the second series (circle), level push-in required
      a mean of 30.44 N, and for pushing 3-mm below cartilage level a mean of 54.33 N
      force had to be used (n = 9). In the control series (1 single graft) the mean
      level push-in force was 38.7 N, and pushing 3 mm deeper required a mean of 86.8 N
      (n = 9). CONCLUSIONS: These results suggest that grafts of greater diameter are
      more stable in absolute values and stability may be increased by shorter dilation
      length, whereas level push-in forces do not increase significantly. There is no
      difference in primary stability between grafts implanted in a row or in circular
      fashion, and multiple grafts may not be as stable as single grafts in the initial
      period after transplantation. CLINICAL RELEVANCE: This is a randomized,
      controlled in vitro animal trial that helps us to better understand the primary
      stability of osteochondral grafts and to refine surgical techniques as well as
      postoperative protocols.

PMID- 16581453
TI  - A biomechanical comparison of the FasT-Fix meniscal repair suture system and the
      RapidLoc device in cadaver meniscus.
AB  - PURPOSE: This biomechanical study compared the fixation characteristics of
      horizontally or vertically implanted FasT-Fix devices (Smith & Nephew, Endoscopy
      Division, Andover, MA) consisting of two 5-mm PLLA suture T-bar anchors with a
      pretied self-sliding knot (No. 0 nonabsorbable, USP, braided polyester suture
      material) and the RapidLoc device (Mitek Surgical Products, Westwood, MA)
      consisting of a PLLA T-bar anchor or "backstop," a connecting suture (No. 2
      nonbiodegradable Ethibond; Ethicon, Somerville, NJ), and a PLLA grommet, for
      repairing posterior third lesions in human menisci. TYPE OF STUDY: Controlled
      laboratory biomechanical study. METHODS: After repair of a vertical longitudinal
      meniscus lesion with either vertically or horizontally implanted FasT-Fix devices
      or RapidLoc devices, 3 groups of 6 specimens underwent cyclic loading (5
      mm/minute, cycling between 5 and 50 N at 1 Hz for 500 cycles) before load to
      failure testing on a servo hydraulic device. One-way analysis of variance and
      Tukey HSD post hoc tests were used to evaluate group differences (P < .05).
      RESULTS: The vertical FasT-Fix device group (3.2 +/- 0.49 mm) had less
      displacement after cyclic testing than either the horizontal FasT-Fix (4.4 +/-
      0.73 mm, P = .003) or the RapidLoc (4.6 +/- 0.22 mm, P = .002) device groups. The
      vertical FasT-Fix device group had greater stiffness during cyclic testing (14.4
      +/- 2.1 N/mm) than the horizontal FasT-Fix (10.4 +/- 1.6 N/mm, P = .0001) or the
      RapidLoc (9.7 +/- 0.44 N/mm, P = .0001) device groups. During load to failure
      testing, the vertical FasT-Fix group (125.3 +/- 39 N) had 28% greater strength
      than the horizontal FasT-Fix device group (89.7 +/- 14 N, P = .02) and 30%
      greater strength than the RapidLoc device group (87.1 +/- 13 N, P = .028),
      whereas displacement and stiffness did not show statistically significant group
      differences. CONCLUSIONS: The vertical FasT-Fix group had superior biomechanical
      characteristics for meniscal fixation during cyclic and load to failure testing
      compared with horizontal FasT-Fix or RapidLoc devices. CLINICAL RELEVANCE:
      Although the RapidLoc devices provided fixation characteristics comparable to
      horizontally implanted FasT-Fix devices, vertically implanted FasT-Fix devices
      may provide superior all-inside fixation.

PMID- 16581455
TI  - The structural properties of an osteochondral cylinder graft-recipient construct
      on autologous osteochondral transplantation.
AB  - PURPOSE: The purpose of this study was to investigate the changes in structural
      properties of an osteochondral cylinder graft-recipient construct after
      autologous osteochondral transplantation. METHODS: A full-thickness cylindrical
      osteochondral defect (5 mm in diameter and 3 mm in depth) was made on the femoral
      condyle of a mature female Japanese white rabbit using the Osteochondral
      Autograft Transfer System (OATS; Arthrex, Naples, FL). The defect was repaired
      with an osteochondral plug (6 mm in diameter and 3 mm in depth) taken from the
      contralateral femoral condyle using the OATS. The implanted osteochondral grafts
      were evaluated immediately after surgery and at postoperative weeks 1, 3, 8, and
      12. The stiffness of articular cartilage was analyzed using a tactile sensor
      system (AXIOM, Fukushima, Japan), which measures stiffness based on changes in
      resonance frequency when a vibrating tactile sensor touches articular cartilage.
      The specimens were stained with hematoxylin and eosin and serial sections were
      examined microscopically. RESULTS: The cartilage stiffness of the graft
      immediately after surgery was 107,695.1 N/m, which was not statistically
      different from the normal cartilage stiffness (100,027.5 N/m). The stiffness at
      postoperative weeks 1, 3, 8, and 12 was 95,386.8, 92,899.3, 95,969.8, and
      104,683.7 N/m, respectively. The stiffness at postoperative weeks 1, 3, and 8 was
      significantly lower than the normal cartilage stiffness and the stiffness at
      postoperative week 12 was the same as normal cartilage. A new bone formation with
      an increase of bone trabeculae between the osteochondral cylinder graft and the
      recipient was observed at postoperative weeks 1, 3, and 8. Thereafter, at
      postoperative week 12, bone trabeculae decreased to the same level as observed in
      a normal model due to the progress of bone remodeling. CONCLUSIONS: The stiffness
      of articular cartilage of the osteochondral graft was normal at the time the
      graft was initially placed and at postoperative week 12. However, the stiffness
      at postoperative weeks 1, 3, and 8 was lower than the normal cartilage stiffness.
      CLINICAL RELEVANCE: Care should be taken when planning the rehabilitation program
      at an early phase after osteochondral transplantation.

PMID- 16581456
TI  - Is the bare spot a consistent landmark for shoulder arthroscopy? A study of 20
      embalmed glenoids with 3-dimensional computed tomographic reconstruction.
AB  - PURPOSE: Our aim was to test a published methodology for arthroscopically
      quantifying glenoid bone loss for its dependability in a cadaver-based anatomic
      study with 3-dimensional (3-D) computed tomographic (CT) reconstructions of 20
      embalmed glenoids. METHODS: Manual macroscopic measurements were made in a
      standardized fashion. In addition, we marked the center of the visible bare spot
      in 20 embalmed glenoids with a titanium pin. The shoulder joints were carefully
      selected for intact rotator cuff, missing capsule-labral deficiency, and absence
      of severe cartilage degeneration. 3-D reconstructed CT scans were evaluated for
      consistency of the bare spot. RESULTS: The mean distance from the bare spot to
      the anterior margin measured manually was 10.9 mm (CT-based, 13.9 mm), to the
      posterior margin 13.7 mm (CT-based, 16.4 mm), and to the inferior margin 9.7 mm
      (CT-based, 15.1 mm). Distances were significantly different. CONCLUSIONS: The
      bare spot did not prove its consistency in 20 carefully selected specimens.
      Therefore, we conclude that this methodology is not a reliable way to
      intraoperatively determine bony glenoid deficiency. CLINICAL RELEVANCE: We
      recommend preoperative bilateral CT scans for evaluation of bony glenoid
      deficiency for exact quantification of the bone loss.

PMID- 16581457
TI  - Comparison of initial mechanical properties of 4 hamstring graft femoral fixation
      systems using nonpermanent hardware for anterior cruciate ligament
      reconstruction: an in vitro animal study.
AB  - PURPOSE: To compare the initial mechanical characteristics of 4 systems used to
      fix tendons to the femur during anterior cruciate ligament reconstruction.
      METHODS: A total of 32 porcine femurs were used to study the following fixation
      systems: Bioabsorbable interference screw (Stryker, Kalamazoo, MI), Bio-Transfix
      Cross-pin (Arthrex, Naples, FL), Biosteon Cross-pin (Stryker), and a fixation
      technique based on wrapping the graft around the femoral condyle itself, thus
      allowing it to be fixed in place without the use of any hardware. The mechanical
      characteristics of each system were obtained by a preconditioned failure tensile
      test. RESULTS: The yield load values (990.9 +/- 242.6 N for Bio-Transfix, 905.1
      +/- 158.8 N for Biosteon Cross-pin, 684.4 +/- 119.7 N for the without-hardware
      system (WHS), and 369.4 +/- 120.1 N for the interference screw) revealed
      significant differences between the techniques that used cross-pins and the other
      2 techniques (P < .006) on the one hand, and between the without hardware
      technique and the interference screw (P < .004) on the other. The stiffness of
      the 2 cross-pin fixation systems (117.6 +/- 22.5 N for Bio-Transfix and 112.6 +/-
      22.5 N for Biosteon) was greater (P < .01) than those of the other systems (79.4
      +/- 15.2 N for the WHS and 68.5 +/- 13 N for the interference screw).
      CONCLUSIONS: The initial biomechanical properties of the 2 cross-pin fixation
      systems proved to be superior to those of the other 2 systems studied. The WHS
      fixation system exhibited better mechanical properties than its interference
      screw counterpart. CLINICAL RELEVANCE: The better initial mechanical
      characteristics encountered using the Bio-Transfix and Biosteon Cross-pin systems
      indicate that these systems are better equipped to bear the loads generated by
      aggressive rehabilitation. The WHS fixation system provides an alternative to
      interference screw fixation.

PMID- 16581458
TI  - Tissue engineering for anterior cruciate ligament reconstruction: a review of
      current strategies.
AB  - The anterior cruciate ligament (ACL) is one the most commonly injured ligaments
      of the knee. Chronic ACL insufficiency can result in episodic instability,
      chondral and meniscal injury, and early osteoarthritis. The intra-articular
      environment of the ligament precludes normal healing and surgical replacement of
      the injured ligament is often mandated to restore stability. Current surgical
      strategies include the use of local autograft or allograft tissues for ligament
      reconstruction. These procedures have yielded superior long-term clinical results
      yet have the potential for serious associated morbidities. Existing limitations
      have prompted ongoing research designed to engineer a replacement ligament that
      will parallel the native ACL in both its biologic properties and mechanical
      durability. Ligament engineering necessitates the use of appropriate source cells
      and a growth matrix to support cell proliferation and collagen synthesis. The
      identification of appropriate growth modulators including both biochemical
      factors and mechanical stimuli are requisites for successful tissue growth. The
      characterization of the elements essential for successful graft development
      represents a significant challenge for investigators. This review examines the
      current literature regarding the potential and limitations of ligament
      engineering and describes the development of a novel 3-dimensional scaffold and
      bioreactor system at our institution.

PMID- 16581459
TI  - Antibiotic prophylaxis for arthroscopic surgery.
AB  - Because the incidence of infection in arthroscopic surgery is very low, one can
      argue both for and against the use of prophylactic antibiotics. Administering
      antibiotics adds expense and introduces the potential for both exposure to
      allergic reactions and selection of resistant organisms. Antibiotics are given to
      prevent deep infection; such treatment may require further surgery, prolonged use
      of intravenous antibiotics, high costs, and outcomes that may be less than
      satisfactory. An answer to this controversial issue would require a study that
      includes large numbers of patients to make it adequately statistically powered
      because the incidence of infection is so low. No such research has yet been
      performed, and the American Academy of Orthopaedic Surgeons (AAOS) has not
      produced an advisory statement addressing this issue. It is the opinion of this
      author that antibiotic prophylaxis is indicated for arthroscopic surgery. Despite
      surgical team best practices, mistakes can occur. This has led the AAOS to issue
      an advisory statement to prevent wrong-site surgery. Similarly, complacency with
      repetition may produce breaks in sterility that may occasionally go undetected.
      Antibiotic usage may help to reduce infection in such circumstances. Arthroscopic
      procedures are not always performed in healthy patients. The risk of infection in
      "high-risk" patients, such as those with diabetes, immune problems, and skin
      disorders, may be reduced by prophylactic antibiotics. How one defines a case as
      arthroscopic can be debated. If small incisions are made, or if the scope is used
      for only a portion of the procedure, many would still consider the case to be
      arthroscopic. Surgeries are becoming more complex, which adds to their duration.
      Some cases also involve the use of implants such as interference screws and
      suture anchors. It is my opinion that antibiotics should be used in these
      situations. The potential exists for litigation in cases of infection.
      Medicolegally, it is easier to argue that all measures were taken to prevent
      infection if prophylactic antibiotics were given, although patient care issues
      supersede defensive medicine. Risk of infection in arthroscopic surgery is
      multifactorial, and antibiotic prophylaxis is only one facet of the issue.
      Although it is my opinion that antibiotics are recommended, others could be
      justified in supporting the opposite opinion, pending appropriately designed and
      adequately powered future investigations.

PMID- 16581460
TI  - An unusual meniscal ganglion cyst that triggered recurrent hemarthrosis of the
      knee.
AB  - A 58-year-old woman suffered spontaneous recurrent hemarthrosis of the knee. In
      the clinical course, pigmented villonodular synovitis was mostly suspected, but
      in arthroscopic surgery the lateral meniscus appeared to be upturned and stuck
      into the lateral pouch with the meniscal ganglion cyst. It was suggested that
      meniscal tear with meniscal ganglion cyst was related with recurrent
      hemarthrosis. Generally, both the meniscal ganglion cysts and spontaneous
      recurrent hemarthrosis are highly rare conditions. In this case, we speculated
      that a negligible power could induce the meniscal tear with recurrent
      hemarthrosis in the particular situation in which the meniscal ganglion cyst
      existed. In other words, the meniscal ganglion cyst might basically and
      physically relate with hemorrhagic condition. Arthroscopically, the meniscal
      ganglion cyst was removed together with the anterior segment of the lateral
      meniscus. Recurrent hemarthrosis was treated successfully by resection of the
      meniscus.

PMID- 16581461
TI  - Engaging needles: a simple technique for arthroscopic side-to-side rotator cuff
      repair.
AB  - We propose that the tibial remnant of the anterior cruciate ligament (ACL) is
      able to enhance the revascularization and cellular proliferation of the graft, to
      preserve proprioceptive function, and to acquire anatomic placement of the graft
      without roof impingement. Therefore, it seems reasonable to assume that
      preserving the tibial remnant as much as possible as a source of reinnervation,
      if technically possible without causing impingement, would be of potential
      benefit to the patient. Our surgical technique was developed to maximize the
      preservation of the tibial remnant. The distally attached semitendinosus and
      gracilis tendons are harvested using a tendon stripper. Once satisfactory
      placement of 2 guide pins convergently is done, create a closed-end socket in the
      lateral femoral condyle with an adequate sized curved curette. For anatomic
      placement of the graft, the tibial tunnel should be positioned within the
      boundaries of the normal ACL tibial remnant. The reamer must be advanced very
      carefully to minimize injury to the residual remnant at the intra-articular
      margin of the tibial tunnel. Penetration should stop at the base of the stump.
      The folded grafts are then pulled intra-articularly through the tibial tunnel,
      the tibial remnant, and the femoral socket by pulling sutures under arthroscopic
      visualization. The ACL tibial remnant is compacted by the tendon passage. The
      graft is secured proximally by tying sutures in the lateral femoral condyle and
      distally at the tibia with double staples using a belt-buckle method. The
      advantages of our technique include maximal preservation of the tibial remnant,
      no roof impingement from intrasynovial anatomic placement of the graft, the
      simplicity of the procedure, the minimal need for hardware or special
      instruments, the economic benefit, and the potential prevention of tibial tunnel
      enlargement by preventing synovial fluid leakage.

PMID- 16581462
TI  - Medial meniscal tears and spontaneous osteonecrosis of the knee.
AB  - We report on a series of 5 patients over 60 years of age who had a symptomatic
      medial meniscus degenerative tear followed-up with magnetic resonance imaging
      (MRI) sequence without arthroscopic surgery who developed spontaneous
      osteonecrosis of the knee. The average patients age was 68 years. Clinically, all
      5 patients had tenderness at the medial joint line. At initial evaluation, MRI
      studies showed degenerative tears of the posterior horn of the medial meniscus
      with no evidence of osteonecrosis. After a mean time of 2.7 months, all patients
      had increased pain and were re-evaluated with a second MRI study that showed
      images compatible with osteonecrosis. The size of the osteonecrotic image shown
      on the MRI was measured, and values obtained averaged 21% of the femoral condyle
      with a range from 17% to 26%. Development of osteonecrosis after arthroscopic
      partial meniscectomy has been previously reported as a rare and unexpected
      complication. We report an MRI sequence between medial meniscus degenerative
      tears and the development of spontaneous osteonecrosis without any arthroscopic
      procedure. Elderly patients with medial meniscal tears should be alerted of this
      potential sequence of events and the impossibility for the surgeon to predict or
      prevent this situation at this stage, especially before performing an
      arthroscopic meniscectomy.

PMID- 16581463
TI  - Arthroscopic synovectomy of the knee joint in rheumatoid arthritis: surgical
      steps for complete synovectomy.
AB  - For successful arthroscopic total synovectomy in rheumatoid arthritis of the
      knee, proper sequential steps are required. First, we resect hypertrophied
      synovial villi on the intercondylar notch to make a gateway for the posterior
      compartments. We also perform synovectomy at the posterolateral chamber because
      of the narrower space of the chamber than that of the posteromedial chamber and
      the intra-articular crowding due to swollen synovial villi with the passage of
      operation time. Special care should be taken not to overlook both posterior back
      corners and roofs, which cannot be seen through the transnotch view, even with a
      70 degrees arthroscope. The posterior back corners and roofs can be visualized by
      using the trans-septal approach technique. In this approach, we prefer to
      perforate the posterior septum in the posterolateral-to-posteromedial direction
      to avoid damaging the neurovascular structures because the structures are located
      just behind and lateral to the midline septum and the posteromedial capsule
      bulges a bit more posteriorly than the posterolateral capsule. Attention is then
      directed to the medial, lateral, and suprapatellar compartments, and finally the
      retropatellar compartment. Our surgical steps are safe and effective for complete
      synovectomy of the rheumatoid arthritic knee joint and other synovial disorders.

PMID- 16581464
TI  - Arthroscopic patellar release for the treatment of chronic patellar tendinopathy.
AB  - We describe an arthroscopic technique for the treatment of chronic patellar
      tendinopathy (jumper's knee). Preoperatively, tendon necrosis or rupture is
      excluded by sonography. Diagnostic arthroscopy is performed and hypertrophic
      synovitis around the inferior patellar pole is removed with a bipolar cautery
      system. Two outside-in cannulas mark the clinically symptomatic region, mainly
      found between the tendon insertion site and the lateral aspects of the patellar
      tendon. The bipolar cautery is used for a release of the paratenon and a bone
      denervation at the inferior patellar pole including the tendon insertion site
      within the marked area. No tendon or bone material is removed or excised
      throughout the procedure. We treated 15 athletes with stage 3 and 4 chronic
      patellar tendinopathies on a modified version of the Blazina score (0-5).
      Patients' mean age was 29 years and the mean follow-up period was 41 months. In
      13 cases, clinical symptoms subsided completely within 3 months after surgery.
      The mean preoperative Blazina score was 3.7 (SD, 0.5) and the mean postoperative
      Blazina score was 0.4 (SD, 1.0; paired 2-tailed t test, P < .01). Ultrasound
      showed a reduction of tendon edema within 3 weeks and no signs of edema within a
      mean period of 5 weeks after surgery. The minimal surgical impact to the tendon
      allows early and functional rehabilitation. The technique is effective, easy to
      perform, and safe to apply.

PMID- 16581465
TI  - Anterior cruciate ligament augmentation procedure with a 1-incision technique:
      anteromedial bundle or posterolateral bundle reconstruction.
AB  - Arthroscopic examination before anterior cruciate ligament (ACL) reconstruction
      sometimes reveals that there is a relatively thick ACL remnant bridging the femur
      and the tibia that may function to stabilize the knee, although its attachment is
      not the same as the anatomic site. We have established an ACL augmentation
      procedure that preserves the ACL remnant with the 1-incision technique using an
      autogenous semitendinosus tendon and EndoButton-CL (Acufex, Smith & Nephew,
      Mansfield, MA) instead of ACL reconstruction. When the ACL remnant was attached
      to the anteroinferior portion of the anatomic femoral origin and the
      posterolateral (PL) bundle was well preserved, the anteromedial (AM) bundle was
      reconstructed. When, in contrast, the ACL remnant was attached to the high-noon
      position with a well-preserved AM bundle, the PL bundle should be reconstructed.
      We have performed 13 AM bundle reconstructions and 4 PL bundle reconstructions.
      The merits of our ACL augmentation procedure are (1) it is performed under
      arthroscopy with 1 incision, (2) it avoids resection of the ACL remnant, which
      contributes to prevention of anterior laxity, (3) it preserves the ACL remnant's
      neural elements and mechanoreceptors, and (4) it provides a favorable influence
      on vascularity and reinnervation to the graft.

PMID- 16581466
TI  - New technique of arthroscopic triple arthrodesis.
AB  - Triple arthrodesis is a common procedure in foot and ankle surgery. It has a
      significant role in treating hind foot osteoarthrosis and deformity. We describe
      a new arthroscopic approach of triple arthrodesis. Through carefully planned
      portal placement of midtarsal joint arthroscopy, together with subtalar
      arthroscopy, we can denude articular cartilage of the 3 joints with minimal
      resection of subchondral bone. The 3 joints are put into the desired position and
      fixed with cannulated screws. This has the potential advantage of minimal bone
      removal and better fusion surface preparation, especially of the talonavicular
      joint.

PMID- 16581470
TI  - How to use cuff suture instruments: the concept of concave in and concave out.

PMID- 16581467
TI  - Clinical evaluation of arthroscopically assisted anterior cruciate ligament
      reconstruction: patellar tendon versus gracilis and semitendinosus autograft.

PMID- 16581474
TI  - Quantitative adenosine real-time myocardial contrast echocardiography for
      detection of angiographically significant coronary artery disease.
AB  - BACKGROUND: Real-time (RT) myocardial contrast echocardiography (MCE) is a novel
      method for assessment of regional myocardial perfusion. We sought to evaluate the
      feasibility and diagnostic accuracy of quantitative adenosine RT MCE in
      predicting significant coronary stenoses, with reference to quantitative coronary
      angiography. METHODS: Low-power RT MCE was performed in 43 patients scheduled for
      quantitative coronary angiography. Peak signal intensity (A), rate of signal
      intensity increase (beta), A x beta (myocardial blood flow), and their hyperemic
      reserves were estimated and compared with angiographic data. RESULTS: The
      feasibility of quantitative stress RT MCE covering all coronary territories was
      77% of patients with adequate baseline image quality. At rest we found no
      significant difference for any of the perfusion parameters between the normal and
      stenosed coronary territories. During hyperemia, beta and A x beta, but not A,
      increased significantly in normal coronary territories. In the regions subtended
      by significantly stenosed arteries, there were no significant increases in beta
      and A x beta. Receiver operating characteristic curves indicated that beta- and A
      x beta-reserves, but not A-reserve, could be sensitive parameters for detecting
      flow-limiting coronary stenosis in selected patients, particularly if significant
      left anterior descending coronary artery disease was involved. CONCLUSION:
      Quantitative assessment of myocardial blood flow and its velocity reserve by RT
      MCE has the potential to detect significant coronary artery disease, but because
      of imaging and technical problems it is not yet robust enough for clinical use in
      unselected patients.

PMID- 16581476
TI  - Automated quantification of the spatial extent of perfusion defects and viability
      on myocardial contrast echocardiography.
AB  - The spatial extent of hypoperfusion or viability is important in the treatment of
      patients with coronary artery disease. We hypothesized that computerized pixel
      intensity threshold analysis (PITA) could be used for the automated analysis of
      perfusion defect size during myocardial contrast echocardiography (MCE). For
      calibration studies, MCE was performed in 6 dogs undergoing ischemia and
      reperfusion. Infarct size was determined by PITA, which automatically calculates
      the percentage of pixels within the myocardium that fail to exceed a
      predetermined threshold of maximum contrast enhancement. A threshold of 10% of
      maximum yielded infarct sizes that most closely correlated with those determined
      by histologic staining. For clinical validation, MCE was performed in 30 patients
      with acute myocardial infarction before primary percutaneous coronary
      intervention (PCI) for measurement of risk area; and within 5 days and at 4 weeks
      after PCI to determine infarct size. The defect size by PITA with a 10% threshold
      value closely correlated with those measured by expert reader planimetry on
      background-subtracted color-coded image sets (r = 0.95, P < .001). We conclude
      that automated analysis of perfusion defect size on MCE is possible by PITA. This
      technique may be useful for rapid and objective analysis of the extent of
      ischemia and viability, and for clinical experimentation where accurate and
      sequential analysis of perfusion defect size is imperative.

PMID- 16581477
TI  - Coronary blood flow after cold exposure and the effect of warm-up exercise.
AB  - BACKGROUND: Cold pressor test (CPT) results indicate that coronary blood flow
      (CBF) increases after sudden cold exposure. Traditionally, warm-up exercise (WEx)
      has been recommended before cold exposure; however, the physiologic effects of
      WEx on CBF have not been elucidated. Therefore, this study was undertaken to
      evaluate the effect of WEx on CBF after cold exposure. METHODS: Fifteen healthy
      young men were enrolled in this study. CBF at the distal left anterior descending
      coronary artery was assessed by transthoracic Doppler echocardiography at
      baseline and after CPT. The same measurements were made with WEx and weight
      bearing exercise before CPT after a 20-minute recovery period between each
      measurement. In the CBF velocities, the time-velocity integral of diastolic flow
      (Dtvi) was measured in addition to blood pressure and heart rate (HR). RESULTS:
      The product of Dtvi x HR increased significantly after CPT. Increments in Dtvi x
      HR after CPT with WEx before CPT were significantly higher than CPT alone (130 +/
      82% vs 68 +/- 37%, P < .05). However, increments in Dtvi x HR after CPT with
      weight-bearing exercise before CPT were not significantly different from those
      observed for CPT alone (74 +/- 50% vs 68 +/- 37%, P = not significant).
      CONCLUSION: Our study suggests that WEx can augment an increased CBF after cold
      exposure. This augmentation of CBF increase after cold exposure may help the body
      meet increased physiologic demands imposed on it by cold exposure. However, this
      phenomenon was not observed for anaerobic weight-bearing exercise.

PMID- 16581475
TI  - Relation between flow reserve capacity of penetrating intramyocardial coronary
      arteries and myocardial fibrosis in hypertension: study using transthoracic
      Doppler echocardiography.
AB  - OBJECTIVE: The purpose of this study was to compare coronary flow reserve (CFR)
      capacity of penetrating intramyocardial coronary artery (PICA) using
      transthoracic Doppler echocardiography and biochemical marker of myocardial
      fibrosis in hypertension (HTN). METHODS: In 58 patients (male:female ratio =
      31:27; mean age 47 +/- 9 years) with chest pain and normal coronary angiogram
      findings, the width of color Doppler signal and peak diastolic velocity of PICA
      flow were measured in the myocardium just beneath the apical impulse window using
      transthoracic Doppler echocardiography. PICA-CFR and PICA-width ratio were
      calculated as the ratio of hyperemic to baseline peak diastolic velocity and as
      the ratio of hyperemic to baseline width after the adenosine infusion (140
      mug/kg/min), respectively. Serum carboxy-terminal propeptide of procollagen type
      I, as a biochemical marker, was measured and patients were divided into 3 groups:
      19 with HTN and PICA-CFR less than 2.0 (group A); 23 with HTN and PICA-CFR of 2.0
      or more (group B); and 16 who were normotensive with PICA-CFR of 2.0 or more
      (group C). RESULTS: Baseline peak diastolic velocity for group A was higher than
      the other two groups (P < .005 vs groups B and C). PICA-width ratio was higher
      than the other two groups (P < .005 vs groups B and C). Serum propeptide of type
      I was 137.1 +/- 16.6 ng/mL in group A, 96.2 +/- 13.7 ng/mL in group B, and 78.8
      +/- 11.2 ng/mL in group C (P < .0001 vs group B and group C). PICA-CFR was
      closely related to serum propeptide of type I (P < .001, r = -0.723). CONCLUSION:
      The impaired PICA-CFR is related to myocardial fibrosis in patients with HTN,
      chest pain, and normal coronary angiogram results.

PMID- 16581478
TI  - Three-dimensional tricuspid annular function provides insight into the mechanisms
      of tricuspid valve regurgitation in classic hypoplastic left heart syndrome.
AB  - BACKGROUND: Tricuspid regurgitation (TR) has a negative impact on outcome in
      hypoplastic left heart syndrome (HLHS). There is a paucity of data assessing the
      mechanisms of TR. Lateral forces from the left ventricle play an important role
      in normal tricuspid valve (TV) function. This study evaluates the role of real
      time 3-dimensional echocardiography in the assessment of the TV annulus and
      subvalvular apparatus in HLHS. METHODS: In all, 31 real-time 3-dimensional
      echocardiographic studies from 26 patients (1 day-17 years old) with classic HLHS
      were included. In all, 7 studies were before and 8 were after first-stage
      palliation; 8 were postcavopulmonary shunt and 8 were post-Fontan. Only patients
      with severe left ventricular attenuation were included. Studies were subdivided
      into two groups: mild TR (N = 20) and severe TR (STR) (N = 11). Data from 17
      control subjects were used for comparison. TV annular area, bending angle (saddle
      shape), and position of anterior papillary muscle were analyzed. RESULTS: All
      annular segments moved in equally during systole in mild TR, whereas septal
      lateral diameter contraction was significantly diminished in STR. TV annular area
      was larger in HLHS (mild TR, 1265 +/- 325; STR, 1767 +/- 450 mm2/m2) than in
      control subjects (762 +/- 85) (P < .001). However, area change was reduced only
      in STR (12.4 +/- 4.6% vs control subjects 20.4 +/- 8.3%, P < .05). Annular shape
      was flat during systole in HLHS. Anterior papillary muscle was laterally
      displaced in STR. CONCLUSIONS: TV annular dynamics were different in patients
      with HLHS as a result of lack of interaction form left ventricle. Annular
      function, especially in septal-lateral direction, was further impaired in STR.

PMID- 16581479
TI  - Noninvasive Doppler tissue measurement of pulmonary artery compliance in children
      with pulmonary hypertension.
AB  - BACKGROUND: We have shown previously that input impedance of the pulmonary
      vasculature provides a comprehensive characterization of right ventricular
      afterload by including compliance. However, impedance-based compliance assessment
      requires invasive measurements. Here, we develop and validate a noninvasive
      method to measure pulmonary artery (PA) compliance using ultrasound color M-mode
      (CMM) Doppler tissue imaging (DTI). METHODS: Dynamic compliance (C(dyn)) of the
      PA was obtained from CMM DTI and continuous wave Doppler measurement of the
      tricuspid regurgitant velocity. C(dyn) was calculated as: [(D(s) - D(d))/(D(d) x
      P(s))] x 10(4); where D(s) = systolic diameter, D(d) = diastolic diameter, and
      P(s) = systolic pressure. The method was validated both in vitro and in 13
      patients in the catheterization laboratory, and then tested on 27 pediatric
      patients with pulmonary hypertension, with comparison with 10 age-matched control
      subjects. C(dyn) was also measured in an additional 13 patients undergoing
      reactivity studies. RESULTS: Instantaneous diameter measured using CMM DTI agreed
      well with intravascular ultrasound measurements in the in vitro models.
      Clinically, C(dyn) calculated by CMM DTI agreed with C(dyn) calculated using
      invasive techniques (23.4 +/- 16.8 vs 29.1 +/- 20.6%/100 mm Hg; P = not
      significant). Patients with pulmonary hypertension had significantly lower peak
      wall velocity values and lower C(dyn) values than control subjects (P < .01).
      C(dyn) values followed an exponentially decaying relationship with PA pressure,
      indicating the nonlinear stress-strain behavior of these arteries. Reactivity in
      C(dyn) agreed with reactivity measured using impedance techniques. CONCLUSION:
      The C(dyn) method provides a noninvasive means of assessing PA compliance and
      should be useful as an additional measure of vascular reactivity subsequent to
      pulmonary vascular resistance in patients with pulmonary hypertension.

PMID- 16581480
TI  - Use of real-time 3-dimensional transthoracic echocardiography in the evaluation
      of mitral valve disease.
AB  - Three-dimensional (3D) echocardiography (3DE) provides unique orientations of the
      mitral valve (MV) not obtainable by routine 2-dimensional echocardiography.
      However, this modality has not been adopted in routine clinical practice because
      of its cumbersome and time-consuming process. The recent introduction of a full
      matrix-array transducer has enabled online real-time 3DE (RT3DE) and rendering.
      This study was designed to: (1) determine the clinical use of RT3DE in patients
      with MV pathology and in a control group selected for their good acoustic windows
      (protocol I); and (2) to investigate the feasibility of imaging the MV apparatus
      in a large group of consecutively imaged patients to determine the acoustic
      window or perspective from which the MV leaflets, commissures, and orifice are
      best visualized (protocol II). In protocol I, 65 patients were selected based on
      MV pathology and good 2-dimensional echocardiography image quality. Protocol II
      included 150 patients who were consecutively imaged using RT3DE. Images were
      viewed online (protocol I) and offline on a digital review station (protocol II).
      RT3DE visualization of the MV apparatus was graded based on the percentage of
      leaflet dropout and definition. In protocol I, 78% of patients had adequate 3D MV
      reconstructions with complete visualization of the anterior mitral leaflet (AML)
      in 84% versus the posterior mitral leaflet (PML) in 77%. The mitral leaflets,
      commissures, and MV orifice were well seen in 98%; however, the submitral
      apparatus was only observed in 76% of the patients. RT3DE: (1) correctly
      identified the prolapsed/flailed scallop in 6 of 8 patients; (2) obtained en face
      orientation of the MV orifice in 9 of 11 patients with mitral stenosis, allowing
      accurate measurements of the orifice area and evaluation of the immediate effects
      of balloon mitral valvuloplasty; and (3) allowed postoperative evaluation of MV
      repair and the integrity of the struts of a bioprosthetic leaflet. In protocol
      II, 70% of patients had adequate RT3DE with complete visualization of the AML
      noted in 55% versus 51% for PML. The mitral leaflets, commissures, and MV orifice
      were observed in 69%. Irrespective of acquisition window, the AML was best seen
      from a ventricular perspective. In contrast, the PML was optimally examined from
      a parasternal window. Both the medial and lateral commissures were equally
      assessed from either imaging window. In conclusion, RT3DE of the MV is feasible
      in a large majority of patients. Using different MV acquisitions RT3DE provides
      important clinical information such as: (1) identification of a prolapsed/flail
      scallop; (2) measurement of stenotic valve areas; (3) evaluation of MV leaflet
      integrity postrepair; and (4) identification of a MV perforation. In general the
      AML is better visualized than the PML. The parasternal window is the optimal
      approach to visualize both AML and PMLs.

PMID- 16581481
TI  - Effect of age and heart rate on atrial mechanical function assessed by Doppler
      tissue imaging in healthy individuals.
AB  - BACKGROUND: The potential usefulness of Doppler tissue imaging (DTI) to assess
      atrial mechanical function in cardiac disease has been demonstrated. However,
      there are few reports on normal values of atrial function by DTI analysis.
      METHODS: Echocardiography with color-coded DTI was performed in 131 healthy
      control subjects. The peak atrial contraction velocity (V(A)) and the timing of
      mechanical events were assessed offline at the left atrial (LA) and right atrial
      (RA) free wall and interatrial septum. RESULTS: V(A) was higher in the RA (9.0 +/
      2.6 cm/s) than the LA (7.5 +/- 2.4 cm/s, P < .001), and both sites were higher
      than the interatrial septum (5.6 +/- 1.3 cm/s, both P < .001). The interatrial
      delay was 24 +/- 21 milliseconds. V(A) at the LA was higher in the participants
      aged 60 years or older than those who were younger than 60 years (8.1 +/- 2.7 vs
      6.7 +/- 1.4 cm/s, P < .001), as was the velocity at the RA (9.6 +/- 2.8 vs 8.0 +/
      2.1 cm/s, P < .01). V(A) at the LA was higher in the participants with heart
      rate of 60/min or higher than those with lower heart rate (7.9 +/- 2.5 vs 6.8 +/-
      1.8 cm/s, P < .05). Sex difference had no effect on V(A) and timings of atrial
      events. CONCLUSIONS: Assessment of atrial mechanical function by DTI is feasible
      in healthy individuals. The V(A) is the highest at the RA, followed by LA, and
      the lowest at the interatrial septum. Older age and faster heart rate seems to
      augment V(A) in the atrial walls.

PMID- 16581482
TI  - Transesophageal echocardiographic assessment of right atrial appendage anatomy
      and function: comparison with the left atrial appendage and implications for
      local thrombus formation.
AB  - OBJECTIVES: We sought to define right atrial appendage (RAA) anatomic and
      functional parameters in a consecutive series of participants and to compare
      these measures with left atrial appendage (LAA) indices among patients with in
      sinus rhythm and atrial fibrillation (AF). BACKGROUND: With AF, both atria are
      fibrillating, yet the vast majority of thrombi are located within the LAA.
      Transesophageal echocardiography provides anatomic and functional information
      regarding both the LAA and the RAA. METHODS: In a consecutive series of 92
      patients (48 men; age 61 +/- 17 years) referred for transesophageal
      echocardiography, RAA and LAA anatomy (width, length, area) and ejection velocity
      were measured at two orientations (RAA, 90 and 135 degrees; LAA, 0 and 90
      degrees). RESULTS: RAA anatomic measures were similar for both imaging planes,
      whereas LAA area was larger at 90 degrees. There was a modest correlation between
      RAA and LAA anatomic measures (area: r = 0.58, P = .001). RAA neck width was
      substantially greater than LAA neck width (P < .0001) whereas appendage area was
      similar (P = not significant) and RAA neck width/area was greater than LAA neck
      width/area (P < .0001). AF was associated with approximately 50% decline in
      ejection velocity for both the LAA and the RAA with an increase in LAA area (P =
      .006 vs sinus), but similar anatomic remodeling was not found for the RAA (P =
      not significant vs sinus). CONCLUSION: In this consecutive series of patients
      undergoing transesophageal echocardiography, RAA anatomic and functional
      parameters were found to be independent of imaging plane, with anatomic measures
      demonstrating a correlation with LAA measures. Although AF is associated with
      depressed RAA and LAA ejection velocities, anatomic RAA remodeling appears to be
      absent. The larger RAA width and lack of anatomic remodeling may partially
      explain the substantially lower prevalence of RAA thrombus found among patients
      with AF.

PMID- 16581483
TI  - Effect of percutaneous mitral balloon valvuloplasty on left atrial appendage
      function: a Doppler tissue study.
AB  - The aim of this study was to compare left atrial appendage (LAA) functions by
      Doppler tissue imaging (DTI) before and after percutaneous balloon mitral
      valvuloplasty (PBMV). Twenty patients with symptomatic rheumatic mitral stenosis
      who underwent PBMV were included in this study. LAA functions were measured
      before and after PBMV. To determine LAA functions, LAA late filling (LAALF)
      velocity, LAA late emptying (LAALE) velocity, and area change of LAA percent were
      measured. In the DTI records, the first positive wave identical to the LAALE wave
      after the P wave was accepted as LAA late systolic wave, and the second negative
      wave identical to the LAALF flow was accepted as late diastolic wave. There was
      no difference in LAALF velocity and area change of LAA percent after PBMV. LAALE
      velocity increased after PBMV compared with baseline (P = .005). Late emptying,
      systolic, and diastolic wave values measured by DTI were found to be increased
      after PBMV compared with baseline (P = .023, P = .002, and P = .002,
      respectively). LAALE velocity measured by standard Doppler was increased after
      PBMV compared with baseline (P = .005), but there was no change in area change of
      LAA percent or LAALF. Spontaneous echocontrast was present in 7 of the 20
      patients before procedure. It completely disappeared (4 patients) or decreased (3
      patients) after procedure. In patients with spontaneous echocontrast, LAALE and
      late emptying, systolic, and diastolic wave values measured by DTI were found to
      be increased after PBMV compared with baseline. Our results suggest that PBMV
      improves LAA functions and, thereby, may have a favorable influence on future
      thromboembolic complications.

PMID- 16581484
TI  - Cardioversion in patients with left ventricular thrombus is not associated with
      increased thromboembolic risk.
AB  - OBJECTIVES: The purpose of the study was to define the incidence of systemic
      embolism after cardioversion in patients with left ventricular (LV) thrombus.
      BACKGROUND: The risk of systemic embolization after cardioversion in patients
      with an atrial thrombus is well known. However, data on thromboembolic events
      after cardioversion in patients with LV thrombus are limited because of hesitance
      to perform cardioversion in this population. METHODS: Transthoracic and
      transesophageal echocardiograms acquired between January 1996 and October 2001 at
      our institution were reviewed for presence of LV thrombus in two orthogonal
      apical views. A total of 413 patients had echocardiographic evidence of LV
      thrombus. Medical records were reviewed for cardioversion performed within 3
      weeks of the echocardiogram. RESULTS: A total of 21 patients, age 66 +/- 10 years
      and ejection fraction 22 +/- 10% were identified. Cardioversion was indicated for
      atrial fibrillation in 8 (38%) and ventricular tachyarrhythmia in 13 (62%)
      patients, and was performed emergently in 5 (24%), electively in 8 (38%), and
      during electrophysiology study in 8 (38%) patients. The time interval between
      diagnostic echocardiographic study and cardioversion was 6 +/- 5 (range 1-18)
      days. All thrombi were located in the apical LV and were described as laminated
      (71%) and protruding (29%), and measured 0.7 +/- 0.4 x 1.6 +/- 0.8 cm. Before
      cardioversion, 17 (81%) patients were anticoagulated with warfarin or heparin.
      During clinical follow-up of up to 1 year (153 +/- 150 days) anticoagulation with
      warfarin was given to 15 (71%) patients. No patient had clinically apparent
      embolic event, including stroke, during hospitalization or during outpatient
      follow-up. CONCLUSIONS: Embolism after cardioversion in patients with
      echocardiographic evidence of LV thrombus was not observed. Cardioversion seems
      to be safe and further prospective studies are needed to address this.

PMID- 16581485
TI  - Right heart function in systemic lupus erythematosus: insights from myocardial
      Doppler tissue imaging.
AB  - The purpose of this study was to use Doppler tissue imaging to evaluate heart
      function and to investigate the correlation between Doppler imaging and pulmonary
      artery systolic pressure (PASP) and right ventricular (RV) ejection fraction (EF)
      in patients with systemic lupus erythematosus (SLE). Standard echocardiography
      and 2-dimensional and color Doppler imaging were used to assess cardiac function
      in patients given the diagnosis of SLE (n = 40) and healthy control subjects (n =
      45). Half of the patients with SLE also presented with pulmonary hypertension
      (PH). Significant differences in PASP and RV EF (RVEF) were found between the
      control and SLE groups. The peak systolic velocity of tricuspid annulus was
      significantly lower in patients with SLE than in the control group. The
      calculated myocardial performance index of the RV, septum, and left ventricular
      lateral wall were significantly higher in patients with SLE than in the control
      group. Bivariate correlation analysis revealed a significant correlation among
      PASP, RVEF, and systolic tricuspid annular velocity. There was a significant
      correlation between each of these 3 parameters and the 6-minute walk distance in
      patients with SLE. Patients with SLE and PH had a significantly shorter 6-minute
      walk distance than patients with SLE without PH. Furthermore, in patients with
      SLE and PH, RVEF and systolic tricuspid annular velocity were lower than in the
      control subjects and patients with SLE without PH. Patients with SLE and PH had a
      longer isovolumic relaxation time and a higher myocardial performance index of RV
      than those without PH. Finally, by simple linear regression analysis, we found a
      significant positive relation between RVEF and systolic tricuspid annular
      velocity, but a negative relationship between PASP and systolic tricuspid annular
      velocity. These findings demonstrate that in patients with SLE, systolic
      tricuspid annular velocity determined by echocardiography and Doppler imaging can
      be used to assess RV function and PASP. Furthermore, systolic tricuspid annular
      velocity reflects exercise tolerance in patients with SLE and the length of the
      isovolumic relaxation time represents the progression of PH.

PMID- 16581486
TI  - Echocardiographic indices of increased left ventricular filling pressure and
      dilation after acute myocardial infarction.
AB  - The relationship between echocardiographic indicators of acute and chronic left
      ventricular (LV) filling pressure and LV dilation after acute myocardial
      infarction was assessed in 47 patients. The ratio of early transmitral flow
      velocity to early mitral annulus velocity (E/e') reflects acute LV filling
      pressure and the indexed volume of the left atrium is an indicator of chronic LV
      filling pressure. E/e' was higher (19 vs 10, P = .001) among patients who
      experienced a greater than 15% increase in indexed LV end-diastolic volume
      (remodeling group, n = 10). Receiver operating characteristic curve analysis
      confirmed that E/e' was a predictor of remodeling (area under the curve 0.83, P =
      .002). Patients with E/e' greater than 15 had a mean increase in indexed LV end
      diastolic volume of 9.3 versus 1.7 mL/m2 in patients with E/e' 15 or less (P =
      .01). Multivariable regression analyses confirmed that E/e' was the strongest
      independent predictor of remodeling in this cohort (odds ratio 1.39, P = .01).
      There was no relationship between indexed volume of the left atrium and LV
      dilation. These data suggest that the E/e' ratio may be a useful predictor of LV
      dilation after acute myocardial infarction. In particular, an E/e' ratio greater
      than 15 identifies patients at increased risk.

PMID- 16581487
TI  - Assessment of stress-induced pulmonary interstitial edema by chest ultrasound
      during exercise echocardiography and its correlation with left ventricular
      function.
AB  - Ultrasound lung comet images (ULC) are useful for the noninvasive assessment of
      extravascular lung water (EVLW). We investigated the modification of EVLW, its
      relation to indices of left ventricular systolic and diastolic function, and
      noninvasively determined pulmonary capillary wedge pressure (PCWP) (PCWP = 1.24
      ratio of early diastolic mitral inflow velocity to early diastolic velocity of
      the mitral annulus [E/Em] + 1.9) at rest and its variation during exercise
      echocardiography. A total of 72 patients (mean age 66.4 +/- 8.4 years) with mean
      ejection fraction of 41.2 +/- 14.4% underwent symptoms-limited exercise
      echocardiography. The sum of the ULC yielded a score of EVLW. The ULC increased
      significantly from baseline to postexercise (5.9 +/- 14.9 vs 11 +/- 20.7, P =
      .0001). Positive linear correlations were found between baseline ULC score and
      baseline ejection fraction (r = -0.37, P = .002), systolic pulmonary artery
      pressure (r = 0.69, P = .0001), E/Em (r = 0.70, P = .0001), and estimated PCWP (r
      = 0.69, P = .0001). The variation between postexercise and baseline ULC score
      correlated significantly with the variation between peak stress and rest PCWP (r
      = 0.62, P = .0001), systolic pulmonary artery pressure (r = 0.44, P = .0001),
      wall-motion score index (r = 0.30, P = .01), and peak stress E/Em (r = 0.71, P =
      .0001), whereas no significant correlations were found between variations of ULC
      score and ejection fraction. This study shows that ULC represents a simple way to
      assess the presence of excess EVLW. Increased EVLW is associated with estimated
      PCWP and indices of left ventricular systolic and diastolic dysfunction. The
      additional exercise-induced increase of PCWP, the worsening of left ventricular
      diastolic function, and extensive wall-motion abnormalities correlate with
      variations of EVLW.

PMID- 16581488
TI  - Assessment of diastolic function with Doppler tissue imaging after cardiac
      surgery: effect of the "postoperative septum" in on-pump and off-pump procedures.
AB  - Doppler tissue imaging (DTI) of mitral annular velocity is useful in assessing
      diastolic function. Most centers record at the septal or lateral segments of the
      annulus. Cardiopulmonary bypass produces changes in the motion of the
      interventricular septum. We evaluated the use of DTI after operation with and
      without cardiopulmonary bypass. 18 patients scheduled for cardiac surgery were
      prospectively examined. Nine underwent cardiopulmonary bypass. Nine had operation
      without bypass. DTI was performed 4 +/- 3 days before operation and again 31+/- 7
      days afterwards. Early diastolic velocities of the lateral and septal segments of
      the mitral annulus were measured. Ejection fraction and transmitral diastolic
      early-to-late filling (E/A) ratios were also assessed. Early diastolic septal
      mitral annular velocity decreased (7.9 +/- 1.2 to 5.9 +/- 1.1 cm/s [P= .001])
      after on-pump operation whereas lateral segment velocity remained unchanged (8.5
      +/- 2.9 to 8.2 +/- 3.7 cm/s [P = .30]). E/A ratio did not change after operation
      (1.28 +/- 0.25 to 1.21 +/- 0.47 [P = .45]). In contrast, septal segment velocity
      in the off-pump group trended higher after operation (5.3 +/- 1.9 to 6.0 +/- 1.5
      cm/s [P = .20]). Lateral segment velocity and E/A ratio also increased somewhat,
      but changes were not significant (6.2 +/- 1.7 to 6.7 +/- 2.9 cm/s [P = .15] and
      1.1 +/- 0.5 to 1.2 +/- 0.4 [P = .13], respectively). Ejection fraction increased
      in both groups. Early diastolic velocity of the septal mitral annulus decreases
      after operation with cardiopulmonary bypass, but does not change after off-pump
      operation. In contrast, early diastolic velocity of the lateral segment is not
      affected by either on-pump or off-pump operation. Measuring lateral segment
      velocity is recommended for diastolic DTI after cardiopulmonary bypass, as septal
      DTI may incorrectly suggest diastolic dysfunction.

PMID- 16581489
TI  - Three-dimensional transthoracic echocardiography to evaluate cor triatriatum in
      the adult.
AB  - Cor triatriatum is a rare congenital condition in which the left atrium is
      partitioned into two chambers by a fibrous or fibromuscular septum. The diagnosis
      is often made early in childhood, but can rarely be discovered later in
      adulthood. This delay in diagnosis is likely because of the number and size of
      the fenestrations in the septum. Echocardiography is the modality most often used
      to diagnose cor triatriatum. Generally, transesophageal echocardiography (TEE) is
      superior to transthoracic imaging. Three-dimensional echocardiography, however,
      is a modality that offers additional information not offered by 2-dimensional
      echocardiography. Although 3-dimensional TEE has previously been described, we
      report what we believe to be the first case of 3-dimensional transthoracic
      echocardiography used to diagnose cor triatriatum. This modality offers an
      advantage over TEE, as it allows the septum to be viewed easily without the risks
      or inconvenience of TEE.

PMID- 16581490
TI  - The Impella Recover LP 5.0 left ventricular assist device: a bridge to coronary
      artery bypass grafting and cardiac transplantation.

PMID- 16581491
TI  - Papillary muscle rupture after blunt chest trauma.
AB  - We report a case of anterolateral papillary muscle rupture in a 22-year-old man
      who had blunt chest trauma caused by a car accident. Transesophageal
      echocardiography revealed severe mitral regurgitation caused by the rupture. He
      successfully underwent emergency mitral valve replacement and was discharged 9
      days after the surgical correction.

PMID- 16581492
TI  - Unusual complication of aortic root reconstruction with sparing of the aortic
      valve: left ventricular outflow tract to right atrial fistula.
AB  - The technique of aortic root reconstruction with sparing of the native aortic
      valve has been adopted in patients with dilatation or dissection of the aortic
      root and normal, functional aortic valve leaflets. We report two patients who
      developed an unusual complication of this surgical procedure: a left ventricular
      outflow tract to right atrial fistula. The clinical presentation of these
      patients, the steps leading to the diagnosis of the fistula, and the mechanism of
      fistula development are outlined. Specific emphasis is placed on
      echocardiographic diagnosis and differential diagnosis of a left ventricular
      outflow tract to right atrial fistula.

PMID- 16581493
TI  - Moyamoya disease associated with Behcet's disease.
AB  - A 32-year-old woman with Behcet's disease suffered repeated transient ischemic
      attacks (TIA) consisting of left hemiparesis. Cerebral angiography revealed the
      typical findings of moyamoya disease, with occlusion of the supraclinoid portion
      of both internal carotid arteries, coupled with abnormal collateral vessels. She
      underwent right superficial temporal artery to middle cerebral artery (STA-MCA)
      anastomosis and encephalomyosynangiosis, due to decreased reserve capacity
      demonstrated on acetazolamide single positron emission computed tomography
      (SPECT). Postoperatively, the TIA symptoms subsided. This is the first report of
      moyamoya disease associated with Behcet's disease, and moyamoya disease should be
      considered in the differential diagnosis of cerebrovascular events in patients
      with Behcet's disease. Revascularization surgery is recommended for the
      prevention of ischemic insults resulting in permanent deficits.

PMID- 16581494
TI  - Stomatopods.

PMID- 16581496
TI  - The prospect of sexual competition stimulates premature and repeated ejaculation
      in a mammal.

PMID- 16581495
TI  - Mosaic and regulative development: two faces of one coin.

PMID- 16581497
TI  - Male development tracks rapidly shifting sexual versus natural selection
      pressures.

PMID- 16581498
TI  - Avian cognition: understanding tool use.
AB  - Although rooks are considered non-tool-using animals, a recent study has shown
      that they learn to solve a 'trap-tube' task faster than many tool-using primates,
      raising questions about the evolution of sophisticated physical cognition.

PMID- 16581499
TI  - Polyploid hybrids: multiple origins of a treefrog species.
AB  - Hyla versicolor, a tetraploid treefrog, is reported to have originated via
      multiple hybridization events involving three diploid ancestors. Its complex
      reticulate history provides insights into the roles that polyploidy and
      hybridization can play in the origin of species.

PMID- 16581500
TI  - Memory: obstacle avoidance without visual cues.
AB  - Avoiding obstacles is essential when we move about the world, yet little is known
      about how we do this when visual cues are not present to guide us. Recent
      evidence from behavioural studies in cats suggests that working memory may be
      crucial.

PMID- 16581501
TI  - Meiosis: checking chromosomes pair up properly.
AB  - Faithful recombination and chromosome segregation in meiosis require regulated
      steps of homolog recognition and association which are monitored by meiotic
      checkpoints. A recent study in the nematode Caenorhabditis elegans has identified
      a checkpoint mechanism that monitors chromosome pairing during meiosis.

PMID- 16581502
TI  - Animal behavior: timing in the wild.
AB  - A recent study has found that Rufous hummingbirds time the interval between
      successive visits to flowers that replenish at different rates. The hummingbirds
      have been shown to store information about both where and when they ate
      throughout the day, evidence that this species has two components of episodic
      memory.

PMID- 16581503
TI  - Metabolic regulation: fasting in the dark.
AB  - It is natural to starve. Learning how animals cope by juggling their scarce
      metabolic resources should therefore allow us to pinpoint physiological switches
      relevant to diabetes and cardiovascular disease. One known environmental trigger
      to metabolic adaptation is darkness; new studies suggest its endocrine mediator
      is 5' AMP.

PMID- 16581504
TI  - Sexual behavior: a seminal peptide stimulates appetites.
AB  - A new study shows that female fruitflies eat more after mating, and that a multi
      functional peptide provided in the seminal fluid of their mates induces this
      behavior. These findings contribute significantly to our understanding of mating
      behaviors and resource allocation, and may provide insights useful for
      controlling the reproduction of insect pests.

PMID- 16581505
TI  - Myopia: the importance of seeing fine detail.
AB  - Eye growth and myopia development are controlled by the retina. What properties
      of the image tell the retina how the eye should grow? A recent study has shown
      that, in chickens, fine details are necessary to prevent the development of
      myopia. Should we carefully avoid any defocus to avoid becoming myopic?

PMID- 16581506
TI  - X-inactivation: close encounters of the X kind.
AB  - X chromosome inactivation ensures equal dosage of X-linked genes between male and
      female mammals. Two new studies have shown that the initiation of inactivation is
      preceded by X chromosome pairing; their results implicate this pairing in the
      choice and counting functions of X chromosome inactivation.

PMID- 16581507
TI  - Postsynaptic mad signaling at the Drosophila neuromuscular junction.
AB  - BACKGROUND: Cell-to-cell communication at the synapse involves synaptic
      transmission as well as signaling mediated by growth factors, which provide
      developmental and plasticity cues. There is evidence that a retrograde,
      presynaptic transforming growth factor-beta (TGF-beta) signaling event regulates
      synapse development and function in Drosophila. RESULTS: Here we show that a
      postsynaptic TGF-beta signaling event occurs during larval development. The type
      I receptor Thick veins (Tkv) and the R-Smad transcription factor Mothers-against
      dpp (Mad) are localized postsynaptically in the muscle. Furthermore, Mad
      phosphorylation occurs in regions facing the presynaptic active zones of
      neurotransmitter release within the postsynaptic subsynaptic reticulum (SSR). In
      order to monitor in real time the levels of TGF-beta signaling in the synapse
      during synaptic transmission, we have established a FRAP assay to measure Mad
      nuclear import/export in the muscle. We show that Mad nuclear trafficking depends
      on stimulation of the muscle. CONCLUSIONS: Our data suggest a mechanism linking
      synaptic transmission and postsynaptic TGF-beta signaling that may coordinate
      nerve-muscle development and function.

PMID- 16581508
TI  - nsf is essential for organization of myelinated axons in zebrafish.
AB  - BACKGROUND: Myelinated axons are essential for rapid conduction of action
      potentials in the vertebrate nervous system. Of particular importance are the
      nodes of Ranvier, sites of voltage-gated sodium channel clustering that allow
      action potentials to be propagated along myelinated axons by saltatory
      conduction. Despite their critical role in the function of myelinated axons,
      little is known about the mechanisms that organize the nodes of Ranvier. RESULTS:
      Starting with a forward genetic screen in zebrafish, we have identified an
      essential requirement for nsf (N-ethylmaleimide sensitive factor) in the
      organization of myelinated axons. Previous work has shown that NSF is essential
      for membrane fusion in eukaryotes and has a critical role in vesicle fusion at
      chemical synapses. Zebrafish nsf mutants are paralyzed and have impaired response
      to light, reflecting disrupted nsf function in synaptic transmission and neural
      activity. In addition, nsf mutants exhibit defects in Myelin basic protein
      expression and in localization of sodium channel proteins at nodes of Ranvier.
      Analysis of chimeric larvae indicates that nsf functions autonomously in neurons,
      such that sodium channel clusters are evident in wild-type neurons transplanted
      into the nsf mutant hosts. Through pharmacological analyses, we show that neural
      activity and function of chemical synapses are not required for sodium channel
      clustering and myelination in the larval nervous system. CONCLUSIONS: Zebrafish
      nsf mutants provide a novel vertebrate system to investigate Nsf function in
      vivo. Our results reveal a previously unknown role for nsf, independent of its
      function in synaptic vesicle fusion, in the formation of the nodes of Ranvier in
      the vertebrate nervous system.

PMID- 16581509
TI  - Behavioral motifs and neural pathways coordinating O2 responses and aggregation
      in C. elegans.
AB  - BACKGROUND: Simple stimuli can evoke complex behavioral responses coordinated by
      multiple neural circuits. O(2) is an important environmental variable for most
      animals. The nematode C. elegans avoids high O(2), and O(2) levels regulate its
      foraging and aggregation. RESULTS: Here, we dissect aggregation and responses to
      O(2) gradients into behavioral motifs and show how O(2) responses can promote
      aggregation. To remain in a group, C. elegans continually modify their movement.
      Animals whose heads emerge from a group will reverse or turn, thereby returning
      to the group. Re-entry inhibits further reversal, aiding retention in the group.
      If an animal's tail exits a group during a reversal, it switches to forward
      movement, returning to the group. Aggregating C. elegans locally deplete O(2).
      The rise in O(2) levels experienced by animals leaving a group induces both
      reversal and turning. Conversely, the fall in O(2) encountered when entering a
      clump suppresses reversal, turning, and high locomotory activity. The soluble
      guanylate cyclases GCY-35 and GCY-36, which are expressed in head and tail
      neurons, promote reversal and turning when O(2) rises. Avoidance of high O(2) is
      also promoted by the TRP-related channel subunits OCR-2 and OSM-9, and the
      transmembrane protein ODR-4, acting in the nociceptive neurons ASH and ADL. Both
      O(2) responsiveness and aggregation can be modified by starvation, but this is
      regulated by natural variation in the npr-1 neuropeptide receptor. CONCLUSIONS:
      Our work provides insights into how a complex behavior emerges from simpler
      behavioral motifs coordinated by a distributed circuit.

PMID- 16581510
TI  - Postmeiotic sex chromatin in the male germline of mice.
AB  - In mammals, the X and Y chromosomes are subject to meiotic sex chromosome
      inactivation (MSCI) during prophase I in the male germline, but their status
      thereafter is currently unclear. An abundance of X-linked spermatogenesis genes
      has spawned the view that the X must be active . On the other hand, the idea that
      the imprinted paternal X of the early embryo may be preinactivated by MSCI
      suggests that silencing may persist longer . To clarify this issue, we establish
      a comprehensive X-expression profile during mouse spermatogenesis. Here, we
      discover that the X and Y occupy a novel compartment in the postmeiotic spermatid
      and adopt a non-Rabl configuration. We demonstrate that this postmeiotic sex
      chromatin (PMSC) persists throughout spermiogenesis into mature sperm and
      exhibits epigenetic similarity to the XY body. In the spermatid, 87% of X-linked
      genes remain suppressed postmeiotically, while autosomes are largely active. We
      conclude that chromosome-wide X silencing continues from meiosis to the end of
      spermiogenesis, and we discuss implications for proposed mechanisms of imprinted
      X-inactivation.

PMID- 16581511
TI  - Concomitant replacement of language and mtDNA in South Caspian populations of
      Iran.
AB  - The Gilaki and Mazandarani occupy the South Caspian region of Iran and speak
      languages belonging to the North-Western branch of Iranian languages . It has
      been suggested that their ancestors came from the Caucasus region, perhaps
      displacing an earlier group in the South Caspian . Linguistic evidence supports
      this scenario, in that the Gilaki and Mazandarani languages (but not other
      Iranian languages) share certain typological features with Caucasian languages .
      We analyzed patterns of mtDNA and Y chromosome variation in the Gilaki and
      Mazandarani. Based on mtDNA HV1 sequences, the Gilaki and Mazandarani most
      closely resemble their geographic and linguistic neighbors, namely other Iranian
      groups. However, their Y chromosome types most closely resemble those found in
      groups from the South Caucasus. A scenario that explains these differences is a
      south Caucasian origin for the ancestors of the Gilaki and Mazandarani, followed
      by introgression of women (but not men) from local Iranian groups, possibly
      because of patrilocality. Given that both mtDNA and language are maternally
      transmitted, the incorporation of local Iranian women would have resulted in the
      concomitant replacement of the ancestral Caucasian language and mtDNA types of
      the Gilaki and Mazandarani with their current Iranian language and mtDNA types.
      Concomitant replacement of language and mtDNA may be a more general phenomenon
      than previously recognized.

PMID- 16581512
TI  - Overexpression of a Drosophila homolog of apolipoprotein D leads to increased
      stress resistance and extended lifespan.
AB  - Increased Apolipoprotein D (ApoD) expression has been reported in various
      neurological disorders, including Alzheimer's disease, schizophrenia, and stroke,
      and in the aging brain . However, whether ApoD is toxic or a defense is unknown.
      In a screen to identify genes that protect Drosophila against acute oxidative
      stress, we isolated a fly homolog of ApoD, Glial Lazarillo (GLaz). In independent
      transgenic lines, overexpression of GLaz resulted in increased resistance to
      hyperoxia (100% O(2)) as well as a 29% extension of lifespan under normoxia.
      These flies also displayed marked improvements in climbing and walking ability
      after sublethal exposure to hyperoxia. Overexpression of Glaz also increased
      resistance to starvation without altering lipid or protein content. To determine
      whether GLaz might be important in protection against reperfusion injury, we
      subjected the flies to hypoxia, followed by recovery under normoxia.
      Overexpression of GLaz was protective against behavioral deficits caused in
      normal flies by this ischemia/reperfusion paradigm. This and the accompanying
      paper by Sanchez et al. (in this issue of Current Biology) are the first to
      manipulate the levels of an ApoD homolog in a model organism. Our data suggest
      that human ApoD may play a protective role and thus may constitute a therapeutic
      target to counteract certain neurological diseases.

PMID- 16581513
TI  - Loss of glial lazarillo, a homolog of apolipoprotein D, reduces lifespan and
      stress resistance in Drosophila.
AB  - The vertebrate Apolipoprotein D (ApoD) is a lipocalin secreted from subsets of
      neurons and glia during neural development and aging . A strong correlation
      exists between ApoD overexpression and numerous nervous system pathologies as
      well as obesity, diabetes, and many forms of cancer . However, the exact
      relationship between the function of ApoD and the pathophysiology of these
      diseases is still unknown. We have generated loss-of-function Drosophila mutants
      for the Glial Lazarillo (GLaz) gene , a homolog of ApoD in the fruit fly, mainly
      expressed in subsets of adult glial cells. The absence of GLaz reduces the
      organism's resistance to oxidative stress and starvation and shortens male
      lifespan. The mutant flies exhibit a smaller body mass due to a lower amount of
      neutral lipids stored in the fat body. Apoptotic neural cell death increases in
      aged flies or upon paraquat treatment, which also impairs neural function as
      assessed by behavioral tests. The higher sensitivity to oxidative stress and
      starvation and the reduced fat storage revert to control levels when a GFP-GLaz
      fusion protein is expressed under the control of the GLaz natural promoter.
      Finally, GLaz mutants have a higher concentration of lipid peroxidation products,
      pointing to a lipid peroxidation protection or scavenging as the mechanism of
      action for this lipocalin. In agreement with Walker et al. (, in this issue of
      Current Biology), who analyze the effects of overexpressing GLaz, we conclude
      that GLaz has a protective role in stress situations and that its absence reduces
      lifespan and accelerates neurodegeneration.

PMID- 16581514
TI  - What image properties regulate eye growth?
AB  - The growth of the eye, unlike other parts of the body, is not ballistic. It is
      guided by visual feedback with the eventual aim being optimal focus of the
      retinal image or emmetropization . It has been shown in animal models that
      interference with the quality of the retinal image leads to a disruption to the
      normal growth pattern, resulting in the development of refractive errors and
      defocused retinal images . While it is clear that retinal images rich in pattern
      information are needed to control eye growth, it is unclear what particular
      aspect of image structure is relevant. Retinal images comprise a range of spatial
      frequencies at different absolute and relative contrasts and in different degrees
      of spatial alignment. Here we show, by using synthetic images, that it is not the
      local edge structure produced by relative spatial frequency alignments within an
      image but rather the spatial frequency composition per se that is used to
      regulate the growth of the eye. Furthermore, it is the absolute energy at high
      spatial frequencies regardless of the spectral slope that is most effective.
      Neither result would be expected from currently accepted ideas of how human
      observers judge the degree of image "blur" in a scene where both phase alignments
      and the relative energy distribution across spatial frequency (i.e., spectral
      slope) are important.

PMID- 16581515
TI  - Allocrine modulation of feeding behavior by the Sex Peptide of Drosophila.
AB  - Mating elicits a dramatic reprogramming of female behavior in numerous insect
      species. In Drosophila, this postmating response (PMR) comprises increased egg
      laying rate and reduced sexual receptivity and is controlled by the products of
      the male accessory glands, a family of approximately 80 small peptides
      transferred in the male seminal fluid . Here, we show that copulation strongly
      stimulates female food intake. Remarkably, this change is abolished if the males
      lack a single, small seminal protein, the Sex Peptide (SP). Ectopic expression of
      SP in virgin females mimics the effect of mating on feeding behavior,
      demonstrating that SP is the main agent controlling this behavioral paradigm. Our
      observations identify enhanced feeding behavior as a novel component of the
      Drosophila PMR and suggest that SP represents a molecular link between energy
      acquisition and reproductive investment.

PMID- 16581516
TI  - Investigating physical cognition in rooks, Corvus frugilegus.
AB  - Although animals (particularly tool-users) are capable of solving physical tasks
      in the laboratory , the degree to which they understand them in terms of their
      underlying physical forces is a matter of contention. Here, using a new paradigm,
      the two-trap tube task, we report the performance of non-tool-using rooks. In
      contrast to the low success rates of previous studies using trap-tube problems ,
      seven out of eight rooks solved the initial task, and did so rapidly. Instead of
      the usual, conceptually flawed control, we used a series of novel transfer tasks
      to test for understanding. All seven transferred their solution across a change
      in stimuli. However, six out of seven were unable to transfer to two further
      tasks, which did not share any one visual constant. One female was able to solve
      these further transfer tasks. Her result is suggestive evidence that rooks are
      capable of sophisticated physical cognition, if not through an understanding of
      unobservable forces , perhaps through rule abstraction. Our results highlight the
      need to investigate cognitive mechanisms other than causal understanding in
      studying animal physical cognition.

PMID- 16581517
TI  - The tumor suppressors Merlin and Expanded function cooperatively to modulate
      receptor endocytosis and signaling.
AB  - The precise coordination of signals that control proliferation is a key feature
      of growth regulation in developing tissues . While much has been learned about
      the basic components of signal transduction pathways, less is known about how
      receptor localization, compartmentalization, and trafficking affect signaling in
      developing tissues. Here we examine the mechanism by which the Drosophila
      Neurofibromatosis 2 (NF2) tumor suppressor ortholog Merlin (Mer) and the related
      tumor suppressor expanded (ex) regulate proliferation and differentiation in
      imaginal epithelia. Merlin and Expanded are members of the FERM (Four-point one,
      Ezrin, Radixin, Moesin) domain superfamily, which consists of membrane-associated
      cytoplasmic proteins that interact with transmembrane proteins and may function
      as adapters that link to protein complexes and/or the cytoskeleton . We
      demonstrate that Merlin and Expanded function to regulate the steady-state levels
      of signaling and adhesion receptors and that loss of these proteins can cause
      hyperactivation of associated signaling pathways. In addition, pulse-chase
      labeling of Notch in living tissues indicates that receptor levels are
      upregulated at the plasma membrane in Mer; ex double mutant cells due to a defect
      in receptor clearance from the cell surface. We propose that these proteins
      control proliferation by regulating the abundance, localization, and turnover of
      cell-surface receptors and that misregulation of these processes may be a key
      component of tumorigenesis.

PMID- 16581518
TI  - MeCP2-dependent transcriptional repression regulates excitatory
      neurotransmission.
AB  - Mutations in the transcriptional repressor, methyl-CpG binding protein 2 (MeCP2),
      result in a neurodevelopmental disorder called Rett Syndrome (RTT) . Based on the
      neurological phenotypes observed in Rett patients, we examined the potential role
      of MeCP2 in synaptic function. We compared elementary properties of synaptic
      transmission between cultured hippocampal neurons from MeCP2 knockout and wild
      type littermate control mice and found a decrease in the frequency of spontaneous
      excitatory synaptic transmission (mEPSCs) in neurons lacking MeCP2. We also
      detected a significant increase in the rate of short-term synaptic depression. To
      explore whether these functional effects can be attributed to MeCP2's role as a
      transcriptional silencer, we treated cultures with a drug that impairs histone
      deacetylation and examined spontaneous synaptic transmission. Treatment with this
      compound induced a similar decrease in mEPSC frequency in wild-type control
      cultures, but this decrease was occluded in MeCP2-deficient neurons.
      Interestingly, neither the loss of MeCP2 nor the drug treatment resulted in
      changes in mIPSC properties. Finally, by means of a lentivirus expressing Cre
      recombinase, we show that loss of MeCP2 function after neurodevelopment and
      synaptogenesis was sufficient to mimic the decrease in mEPSC frequency seen in
      constitutive MeCP2 KO neurons. Taken together, these results suggest a role for
      MeCP2 in control of excitatory presynaptic function through regulation of gene
      expression.

PMID- 16581519
TI  - Nap1 regulates Dictyostelium cell motility and adhesion through SCAR-dependent
      and -independent pathways.
AB  - SCAR--also known as WAVE--is a key regulator of actin dynamics. Activation of
      SCAR enhances the nucleation of new actin filaments through the Arp2/3 complex,
      causing a localized increase in the rate of actin polymerization . In vivo, SCAR
      is held in a large regulatory complex, which includes PIR121 and Nap1 proteins,
      whose precise role is unclear. It was initially thought to hold SCAR inactive
      until needed , but recent data suggest that it is essential for SCAR function .
      Here, we show that disruption of the gene that encodes Nap1 (napA) causes loss of
      SCAR function. Cells lacking Nap1 are small and rounded, with diminished actin
      polymerization and small pseudopods. Furthermore, several aspects of the napA
      phenotype are more severe than those evoked by the absence of SCAR alone. In
      particular, napA mutants have defects in cell-substrate adhesion and
      multicellular development. Despite these defects, napA(-) cells move and chemotax
      surprisingly effectively. Our results show that the members of the complex have
      unexpectedly diverse biological roles.

PMID- 16581521
TI  - Ships, trucks, and trains: effects of goods movement on environmental health.

PMID- 16581520
TI  - Supra-clavicular lymph node metastatic spread in patients with ovarian cancer
      disclosed at 18F-FDG-PET/CT: an unusual finding.
AB  - Tumoral dissemination of ovarian cancer most commonly occurs through the intra
      peritoneal route; nevertheless, although it is rare, ovarian cancer may also
      metastasise through the lymphatic channels. Lymphatic diffusion of ovarian cancer
      usually involves pelvic and retro-peritoneal lymph nodes. Extra-abdominal lymph
      nodes are rarely involved and their detection may represent a challenge for the
      oncologist. We describe here two patients studied for ovarian cancer by
      [18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography
      (PET)/computed tomography (CT): one case during pre-operative staging, the other
      for restaging after surgery. In both cases PET examination identified
      extraabdominal lymph node tumoral spread in the left supra-clavicular space;
      biopsy led to a final diagnosis of recurrent ovarian cancer. Previous reports in
      the literature on tumoral spread of ovarian cancer to the supra-clavicular nodes
      are rare, however this possible site of metastatic involvement has to be kept in
      mind by oncologists and our data show that the 18F-FDG PET/CT may be useful to
      disclose this unusual supra-diaphragmatic lymphatic diffusion of metastatic
      lymphatic ovarian cancer.

PMID- 16581522
TI  - Translating translational biomedicine for environmental health.

PMID- 16581523
TI  - Coal tar and paving products.

PMID- 16581524
TI  - Organic diets and children's health.

PMID- 16581525
TI  - Translocation of ultrafine particles.

PMID- 16581526
TI  - Evaluating beryllium exposure data.

PMID- 16581527
TI  - U.S. Ocean Policy Report Card.

PMID- 16581529
TI  - Ports in a storm.
AB  - In many parts of the world, shipping-related emissions have already exceeded or
      are expected to soon exceed those from land-based sources. Shipping emissions can
      be reduced substantially by using some of the same technologies being applied to
      land-based sources, including cleaner engines and fuels, exhaust control methods,
      and operational modifications. Various ports are testing the feasibility of these
      mechanisms with varying degrees of success. What is perhaps most greatly needed
      is expedited creation of better regulations at all levels, from the International
      Maritime Organization to port city authorities.

PMID- 16581530
TI  - Unfair trade: e-waste in Africa.
AB  - Africa is quickly becoming a destination for information technology in the form
      of tons of used computers, fax machines, cell phones, and other electronics.
      Although many of these machines can be repaired and resold, up to 75% of the
      electronics shipped to Africa is junk. This equipment, when dumped, may leach
      lead, mercury, and cadmium into the environment; when burned, it may release
      carcinogenic dioxins and polyaromatic hydrocarbons. In the United States,
      activists are working to limit the flow of e-waste to developing countries
      through international agreements and voluntary e-waste export reduction efforts.

PMID- 16581531
TI  - Safe harbor: protecting ports with shipboard fuel cells.
AB  - With five of the largest harbors in the United States, California is beginning to
      take steps to manage the large amounts of pollution generated by these bustling
      centers of transport and commerce. One option for reducing diesel emissions is
      the use of fuel cells, which run cleaner than diesel and other internal
      combustion engines. Other technologies being explored by harbor officials are
      diesel-electric hybrid and gas turbine locomotives for moving freight within port
      complexes.

PMID- 16581533
TI  - Perinatal immunotoxicity: why adult exposure assessment fails to predict risk.
AB  - Recent research has pointed to the developing immune system as a remarkably
      sensitive toxicologic target for environmental chemicals and drugs. In fact, the
      perinatal period before and just after birth is replete with dynamic immune
      changes, many of which do not occur in adults. These include not only the basic
      maturation and distribution of immune cell types and selection against
      autoreactive lymphocytes but also changes designed specifically to protect the
      pregnancy against immune-mediated miscarriage. The newborn is then faced with
      critical immune maturational adjustments to achieve an immune balance necessary
      to combat myriad childhood and later-life diseases. All these processes set the
      fetus and neonate completely apart from the adult regarding immunotoxicologic
      risk. Yet for decades, safety evaluation has relied almost exclusively upon
      exposure of the adult immune system to predict perinatal immune risk. Recent
      workshops and forums have suggested a benefit in employing alternative exposures
      that include exposure throughout early life stages. However, issues remain
      concerning when and where such applications might be required. In this review we
      discuss the reasons why immunotoxic assessment is important for current childhood
      diseases and why adult exposure assessment cannot predict the effect of
      xenobiotics on the developing immune system. It also provides examples of
      developmental immunotoxicants where age-based risk appears to differ. Finally, it
      stresses the need to replace adult exposure assessment for immune evaluation with
      protocols that can protect the developing immune system.

PMID- 16581534
TI  - Monensin improves the effectiveness of meso-dimercaptosuccinate when used to
      treat lead intoxication in rats.
AB  - Among divalent cations, the ionophore monensin shows high activity and
      selectivity for the transport of lead ions (Pb2+) across phospholipid membranes.
      When coadministered to rats that were receiving meso-dimercaptosuccinate for
      treatment of Pb intoxication, monensin significantly increased the amount of Pb
      removed from femur, brain, and heart. It showed a tendency to increase Pb removal
      from liver and kidney but had no effect of this type in skeletal muscle. Tissue
      levels of several physiologic (calcium, cobalt, copper, iron, magnesium,
      manganese, molybdenum, zinc) and nonphysiologic (arsenic, cadmium, chromium,
      nickel, strontium) elements were also determined after the application of these
      compounds. Among the physiologic elements, a number of significant changes were
      seen, including both rising and falling values. The size of these changes was
      typically around 20% compared with control values, with the largest examples seen
      in femur. These changes often tended to reverse those of similar size that had
      occurred during Pb administration. Among the nonphysiologic elements, which were
      present in trace amounts, the changes were smaller in number but larger in size.
      None of these changes appears likely to be significant in terms of toxicity, and
      there were no signs of overt toxicity under any of the conditions employed.
      Monensin may act by cotransporting Pb2+ and OH- ions out of cells, in exchange
      for external sodium ions. The net effect would be to shuttle intracellular Pb2+
      to extracellular dimercaptosuccinic acid thereby enhancing its effectiveness.
      Thus, monensin may be useful for the treatment of Pb intoxication when applied in
      combination with hydrophilic Pb2+ chelators.

PMID- 16581535
TI  - Occupational toluene exposure induces cytochrome P450 2E1 mRNA expression in
      peripheral lymphocytes.
AB  - Print workers are exposed to organic solvents, of which the systemic toxicant
      toluene is a main component. Toluene induces expression of cytochrome P450 2E1
      (CYP2E1), an enzyme involved in its own metabolism and that of other
      protoxicants, including some procarcinogens. Therefore, we investigated the
      association between toluene exposure and the CYP2E1 response, as assessed by mRNA
      content in peripheral lymphocytes or the 6-hydroxychlorzoxazone (6OH
      CHZ)/chlorzoxazone (CHZ) quotient (known as CHZ metabolic ratio) in plasma, and
      the role of genotype (5 -flanking region RsaI/PstI polymorphic sites) in 97 male
      print workers. The geometric mean (GM) of toluene concentration in the air was
      52.80 ppm (10-760 ppm); 54% of the study participants were exposed to toluene
      concentrations that exceeded the maximum permissible exposure level (MPEL). The
      GM of urinary hippuric acid at the end of a work shift (0.041 g/g creatinine) was
      elevated relative to that before the shift (0.027 g/g creatinine; p < 0.05). The
      GM of the CHZ metabolic ratio was 0.33 (0-9.3), with 40% of the subjects having
      ratios below the GM. However, the average CYP2E1 mRNA level in peripheral
      lymphocytes was 1.07 (0.30-3.08), and CYP2E1 mRNA levels within subjects
      correlated with the toluene exposure ratio (environmental toluene
      concentration:urinary hippuric acid concentration) (p = 0.014). Genotype did not
      alter the association between the toluene exposure ratio and mRNA content. In
      summary, with further validation, CYP2E1 mRNA content in peripheral lymphocytes
      could be a sensitive and noninvasive biomarker for the continuous monitoring of
      toluene effects in exposed persons.

PMID- 16581536
TI  - Antiestrogens inhibit xenoestrogen-induced brain aromatase activity but do not
      prevent xenoestrogen-induced feminization in Japanese medaka (Oryzias latipes).
AB  - In fish, exposure to estrogen or estrogen-mimicking chemicals (xenoestrogens)
      during a critical period of development can irreversibly invert sex
      differentiation. In medaka, a male-to-female reversal upon exposure to a
      xenoestrogen is accompanied by an increase in brain aromatase expression and
      activity. However, whether this increase is the direct cause of sex reversal is
      unknown. In this study we further examined the role brain aromatase plays in
      genesis of developmental abnormalities in response to endocrine-disrupting
      chemicals (EDCs). Further, the effects of a mixture of apparent antagonistic
      environmentally relevant EDCs on development were examined to determine if their
      combined actions could lessen each other's impacts. To this end, hatchling medaka
      were subjected in a 2-week flow-through immersion exposure to an estrogen mimic
      [dichlorodiphenyltrichloroethane (o,p -DDT)] and to pharmaceutical [fadrozole
      (FAD)] and environmental aromatase inhibitors [tributyltin (TBT)] alone and in
      combination. Brain aromatase expression and enzyme activity were measured on
      exposure days 5, 9, and 14 by real-time reverse-transcriptase polymerase chain
      reaction and tritiated water release assay, respectively. We recorded sex
      reversals at sexual maturity by examining the phenotypic and genotypic sex of d
      rR-strain medaka. Results indicate that FAD and TBT inhibit aromatase activity in
      o,p -DDT-treated fish but do not prevent feminization, indicating that increased
      brain aromatase activity is not critical to EDC-induced male-to-female sex
      inversion. The observation that estradiol biosynthesis inhibitors do not block
      the effect of the xenoestrogen suggests that in the environment, exposure to
      seemingly antagonistic EDCs does not necessarily lessen the harmful impacts of
      these compounds.

PMID- 16581538
TI  - Changes in breath trihalomethane levels resulting from household water-use
      activities.
AB  - Common household water-use activities such as showering, bathing, drinking, and
      washing clothes or dishes are potentially important contributors to individual
      exposure to trihalomethanes (THMs), the major class of disinfection by-products
      of water treated with chlorine. Previous studies have focused on showering or
      bathing activities. In this study, we selected 12 common water-use activities and
      determined which may lead to the greatest THM exposures and result in the
      greatest increase in the internal dose. Seven subjects performed the various
      water-use activities in two residences served by water utilities with relatively
      high and moderate total THM levels. To maintain a consistent exposure
      environment, the activities, exposure times, air exchange rates, water flows,
      water temperatures, and extraneous THM emissions to the indoor air were carefully
      controlled. Water, indoor air, blood, and exhaled-breath samples were collected
      during each exposure session for each activity, in accordance with a strict, well
      defined protocol. Although showering (for 10 min) and bathing (for 14 min), as
      well as machine washing of clothes and opening mechanical dishwashers at the end
      of the cycle, resulted in substantial increases in indoor air chloroform
      concentrations, only showering and bathing caused significant increases in the
      breath chloroform levels. In the case of bromodichloromethane (BDCM), only
      bathing yielded a significantly higher air level in relation to the preexposure
      concentration. For chloroform from showering, strong correlations were observed
      for indoor air and exhaled breath, blood and exhaled breath, indoor air and
      blood, and tap water and blood. Only water and breath, and blood and breath were
      significantly associated for chloroform from bathing. For BDCM, significant
      correlations were obtained for blood and air, and blood and water from showering.
      Neither dibromochloromethane nor bromoform gave measurable breath concentrations
      for any of the activities investigated because of their much lower tap-water
      concentrations. Future studies will address the effects that changes in these
      common water-use activities may have on exposure.

PMID- 16581537
TI  - Lead increases lipopolysaccharide-induced liver-injury through tumor necrosis
      factor-alpha overexpression by monocytes/macrophages: role of protein kinase C
      and P42/44 mitogen-activated protein kinase.
AB  - Although lead and lipopolysaccharide (LPS), both important environmental
      pollutants, activate cells through different receptors and participate in
      distinct upstream signaling pathways, Pb increases the amount of LPS-induced
      tumor necrosis factor-alpha (TNF-alpha). We examined the cells responsible for
      the excess production of Pb-increased LPS-induced TNF-alpha and liver injury, and
      the roles of protein kinase C (PKC) and p42/44 mitogen-activated protein kinase
      (MAPK) in the induction of TNF-alpha. Peritoneal injection of Pb alone (100
      micromol/kg) or a low dose of LPS (5 mg/kg) did not affect serum TNF-alpha or
      liver functions in A/J mice. In contrast, coexposure to these noneffective doses
      of Pb plus LPS (Pb+LPS) strongly induced TNF-alpha expression and resulted in
      profound liver injury. Direct inhibition of TNF-alpha or functional inactivation
      of monocytes/macrophages significantly decreased the level of Pb+LPS-induced
      serum TNF-alpha and concurrently ameliorated liver injury. Pb+LPS coexposure
      stimulated the phosphorylation of p42/44 MAPK and the expression of TNF-alpha in
      CD14+ cells of cultured mouse whole blood, peritoneal macrophages, and RAW264.7
      cells. Moreover, blocking PKC or MAPK effectively reduced Pb+LPS-induced TNF
      alpha expression and liver injury. In summary, monocytes/macrophages were the
      cells primarily responsible for producing, through the PKC/MAPK pathway, the
      excess Pb-increased/LPS-induced TNF-alpha that caused liver injury. alpha.

PMID- 16581539
TI  - National prevalence and exposure risk for cockroach allergen in U.S. households.
AB  - We characterized the prevalence of cockroach allergen exposure in a nationally
      representative sample of U.S. homes and assessed risk factors for elevated
      concentrations. DESIGN: We used data from the National Survey of Lead and
      Allergens in Housing, a population-based cross-sectional survey. PARTICIPANTS:
      Participants were residents of 831 U.S. homes in the survey.
      EVALUATIONS/MEASUREMENTS: We analyzed allergen, questionnaire, and observational
      data of 831 U.S. homes. RESULTS: Cockroach allergen (Bla g 1) concentrations
      exceed 2.0 U/g, a level associated with allergic sensitization, in 11% of U.S.
      living room floors and 13% of kitchen floors. Concentrations exceed 8.0 U/g, a
      level associated with asthma morbidity, in 3% of living room floors and 10% of
      kitchen floors. Elevated concentrations were observed in high-rise apartments,
      urban settings, pre-1940 constructions, and households with incomes < $20,000.
      Odds of having concentrations > 8.0 U/g were greatest when roach problems were
      reported or observed and increased with the number of cockroaches observed and
      with indications of recent cockroach activity. CONCLUSIONS: Household cockroach
      allergen exposure is characterized in a nationally representative context. The
      allergen is prevalent in many settings, at levels that may contribute to allergic
      sensitization and asthma morbidity. RELEVANCE TO CLINICAL OR PROFESSIONAL
      PRACTICE: Likelihood of exposure can be assessed by consideration of demographic
      and household determinants.

PMID- 16581540
TI  - Methylarsonous acid transport by aquaglyceroporins.
AB  - Many mammals methylate trivalent inorganic arsenic in liver to species that are
      released into the bloodstream and excreted in urine and feces. This study
      addresses how methylated arsenicals pass through cell membranes. We have
      previously shown that aquaglyceroporin channels, including Escherichia coli GlpF,
      Saccharomyces cerevisiae Fps1p, AQP7, and AQP9 from rat and human, conduct
      trivalent inorganic arsenic [As(III)] as arsenic trioxide, the protonated form of
      arsenite. One of the initial products of As(III) methylation is methylarsonous
      acid [MAs(III)], which is considerably more toxic than inorganic As(III). In this
      study, we investigated the ability of GlpF, Fps1p, and AQP9 to facilitate
      movement of MAs(III) and found that rat aquaglyceroporin conducted MAs(III) at a
      higher rate than the yeast homologue. In addition, rat AQP9 facilitates MAs(III)
      at a higher rate than As(III). These results demonstrate that aquaglyceroporins
      differ both in selectivity for and in transport rates of trivalent arsenicals. In
      this study, the requirement of AQP9 residues Phe-64 and Arg-219 for MAs(III)
      movement was examined. A hydrophobic residue at position 64 is not required for
      MAs(III) transport, whereas an arginine at residue 219 may be required. This is
      similar to that found for As(III), suggesting that As(III) and MAs(III) use the
      same translocation pathway in AQP9. Identification of MAs(III) as an AQP9
      substrate is an important step in understanding physiologic responses to arsenic
      in mammals, including humans.

PMID- 16581541
TI  - The exposure-response curve for ozone and risk of mortality and the adequacy of
      current ozone regulations.
AB  - Time-series analyses have shown that ozone is associated with increased risk of
      premature mortality, but little is known about how O3 affects health at low
      concentrations. A critical scientific and policy question is whether a threshold
      level exists below which O3 does not adversely affect mortality. We developed and
      applied several statistical models to data on air pollution, weather, and
      mortality for 98 U.S. urban communities for the period 1987-2000 to estimate the
      exposure-response curve for tropospheric O3 and risk of mortality and to evaluate
      whether a "safe" threshold level exists. Methods included a linear approach and
      subset, threshold, and spline models. All results indicate that any threshold
      would exist at very low concentrations, far below current U.S. and international
      regulations and nearing background levels. For example, under a scenario in which
      the U.S. Environmental Protection Agency's 8-hr regulation is met every day in
      each community, there was still a 0.30% increase in mortality per 10-ppb increase
      in the average of the same and previous days' O3 levels (95% posterior interval,
      0.15-0.45%). Our findings indicate that even low levels of tropospheric O3 are
      associated with increased risk of premature mortality. Interventions to further
      reduce O3 pollution would benefit public health, even in regions that meet
      current regulatory standards and guidelines.

PMID- 16581542
TI  - A survival-adjusted quantal-response test for analysis of tumor incidence rates
      in animal carcinogenicity studies.
AB  - In rodent cancer bioassays, groups of animals are exposed to different doses of a
      chemical of interest and followed for tumor occurrence. The resulting tumor rates
      are commonly analyzed using a survival-adjusted Cochran-Armitage (CA) trend test.
      The CA trend test has reasonable power when the tumor-response curve is linear in
      dose, but it may be underpowered for a nonlinear response. An alternative
      survival-adjusted test procedure based on isotonic regression methodology has
      previously been proposed. Although this alternative procedure performs well when
      the tumor response is nonlinear in dose, it has less power than the CA trend test
      when the response is linear in dose. Here, we introduce a new survival-adjusted
      test procedure that makes use of both the CA trend test and the isotonic
      regression-based trend test. Using a broad range of experimental conditions
      typical of National Toxicology Program (NTP) bioassays, we conducted extensive
      computer simulations to compare the false-positive error rate and power of the
      proposed procedure with the survival-adjusted CA trend test. The new procedure
      competes well with the survival-adjusted CA trend test when observed tumor rates
      are linear in dose and performs substantially better when observed tumor rates
      are nonlinear in dose. Further, the proposed trend test almost always has a
      smaller false-positive rate than does the survival-adjusted CA trend test. We
      also developed an order-restricted inference-based procedure for performing
      multiple pairwise comparisons between each of the dose groups and the control
      group. The trend test and the multiple pairwise comparisons test are demonstrated
      using an example from a study conducted by the NTP.

PMID- 16581543
TI  - The effect of inhaled chromium on different exhaled breath condensate biomarkers
      among chrome-plating workers.
AB  - Chromium is corrosive, cytotoxic, and carcinogenic for humans and can induce
      acute and chronic lung tissue toxicity. The aim of this study was to investigate
      Cr levels in exhaled breath condensate (EBC) of workers exposed to Cr(VI) and to
      assess their relationship with biochemical changes in the airways by analyzing
      EBC biomarkers of oxidative stress, namely, hydrogen peroxide (H2O2) and
      malondialdehyde (MDA). EBC samples were collected from 24 chrome-plating workers
      employed in a chrome-plating plant both before and after the Friday work shift
      and before the work shift on the following Monday. Cr-EBC levels increased from
      the beginning (5.3 microg/L) to the end of Friday (6.4 microg/L) but were
      considerably lower on Monday morning (2.8 microg/L). A similar trend was observed
      for H2O2-EBC levels (which increased from 0.36 microM to 0.59 microM on Friday
      and were 0.19 microM on Monday morning) and MDA-EBC levels (which increased from
      8.2 nM to 9.7 nM on Friday and were 6.6 nM on Monday). Cr-EBC levels correlated
      with those of H2O2-EBC (r = 0.54, p < 0.01) and MDA-EBC (r = 0.59, p < 0.01), as
      well as with urinary Cr levels (r = 0.25, p < 0.05). The results of this study
      demonstrate that EBC is a suitable matrix that can be used to investigate both Cr
      levels and biomarkers of free radical production sampling the epithelial-lining
      fluid of workers exposed to Cr(VI).

PMID- 16581544
TI  - Evolutionary toxicology: population-level effects of chronic contaminant exposure
      on the marsh frogs (Rana ridibunda) of Azerbaijan.
AB  - We used molecular methods and population genetic analyses to study the effects of
      chronic contaminant exposure in marsh frogs from Sumgayit, Azerbaijan. Marsh
      frogs inhabiting wetlands in Sumgayit are exposed to complex mixtures of chemical
      contaminants, including petroleum products, pesticides, heavy metals, and many
      other industrial chemicals. Previous results documented elevated estimates of
      genetic damage in marsh frogs from the two most heavily contaminated sites. Based
      on mitochondrial DNA (mtDNA) control region sequence data, the Sumgayit region
      has reduced levels of genetic diversity, likely due to environmental degradation.
      The Sumgayit region also acts as an ecological sink, with levels of gene flow
      into the region exceeding gene flow out of the region. Additionally, localized
      mtDNA heteroplasmy and diversity patterns suggest that one of the most severely
      contaminated sites in Sumgayit is acting as a source of new mutations resulting
      from an increased mutation rate. This study provides an integrated method for
      assessing the cumulative population impacts of chronic contaminant exposure by
      studying both population genetic and evolutionary effects.

PMID- 16581545
TI  - Profiles of global gene expression in ionizing-radiation-damaged human diploid
      fibroblasts reveal synchronization behind the G1 checkpoint in a G0-like state of
      quiescence.
AB  - Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced
      by ionizing radiation (IR) were quantified in telomerase-expressing human diploid
      fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated
      colony formation by 40-45% in three fibroblast lines; this dose was used in all
      subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from G2 to
      M at 2 hr post-IR and a similarly severe arrest of progression from G1 to S at 6
      and 12 hr post-IR. Normal rates of DNA synthesis and mitosis 6 and 12 hr post-IR
      caused the S and M compartments to empty by > 70% at 24 hr. Global gene
      expression was analyzed in IR-treated cells. A microarray analysis algorithm,
      EPIG, identified nine IR-responsive patterns of gene expression that were common
      to the three fibroblast lines, including a dominant p53-dependent G1 checkpoint
      response. Many p53 target genes, such as CDKN1A, GADD45, BTG2, and PLK3, were
      significantly up-regulated at 2 hr post-IR. Many genes whose expression is
      regulated by E2F family transcription factors, including CDK2, CCNE1, CDC6, CDC2,
      MCM2, were significantly down-regulated at 24 hr post-IR. Numerous genes that
      participate in DNA metabolism were also markedly repressed in arrested
      fibroblasts apparently as a result of cell synchronization behind the G1
      checkpoint. However, cluster and principal component analyses of gene expression
      revealed a profile 24 hr post-IR with similarity to that of G0 growth quiescence.
      The results reveal a highly stereotypic pattern of response to IR in human
      diploid fibroblasts that reflects primarily synchronization behind the G1
      checkpoint but with prominent induction of additional markers of G0 quiescence
      such as GAS1.

PMID- 16581546
TI  - The relationship between ambient air pollution and heart rate variability differs
      for individuals with heart and pulmonary disease.
AB  - Associations between concentrations of ambient fine particles [particulate matter
      < 2.5 microm aerodynamic diameter (PM2.5)] and heart rate variability (HRV) have
      differed by study population. We examined the effects of ambient pollution on HRV
      for 18 individuals with chronic obstructive pulmonary disease (COPD) and 12
      individuals with recent myocardial infarction (MI) living in Atlanta, Georgia.
      HRV, baseline pulmonary function, and medication data were collected for each
      participant on 7 days in fall 1999 and/or spring 2000. Hourly ambient pollution
      concentrations were obtained from monitoring sites in Atlanta. The association
      between ambient pollution and HRV was examined using linear mixed-effect models.
      Ambient pollution had opposing effects on HRV in our COPD and MI participants,
      resulting in no significant effect of ambient pollution on HRV in the entire
      population for 1-, 4-, or 24-hr moving averages. For individuals with COPD,
      interquartile range (IQR) increases in 4-hr ambient PM2.5 (11.65 microg/m3)) and
      nitrogen dioxide (11.97 ppb) were associated with 8.3% [95% confidence interval
      (CI), 1.7-15.3%] and 7.7% (95% CI, 0.1-15.9%) increase in the SD of normal R-R
      intervals (SDNN), respectively. For individuals with MI, IQR increases in 4-hr
      PM2.5 (8.54 microg/m3) and NO2 (9.25 ppb) were associated with a nonsignificant
      2.9% (95% CI, -7.8 to 2.3) and significant 12.1 (95% CI, -19.5 to -4.0) decrease
      in SDNN. Beta-blocker and bronchodilator intake and baseline forced expiratory
      volume in 1 sec modified the PM-SDNN association significantly, with effects
      consistent with those by disease group. Results indicate heterogeneity in the
      autonomic response to air pollution due to differences in baseline health, with
      significant associations for ambient NO2 suggesting an important role for traffic
      related pollution.

PMID- 16581548
TI  - Workgroup report: Review of genomics data based on experience with mock
      submissions--view of the CDER Pharmacology Toxicology Nonclinical
      Pharmacogenomics Subcommittee.
AB  - Over the past few years, both the U.S. Food and Drug Administration (FDA) and the
      pharmaceutical industry have recognized the potential importance of
      pharmacogenomics and toxicogenomics to drug development. To resolve the
      uncertainties surrounding the use of microarray technology and the presentation
      of genomics data for regulatory purposes, several pharmaceutical companies and
      genomics technology providers have provided the FDA with reports of genomics
      studies that included supporting toxicology data (e.g., serum chemistry,
      histopathology). These studies were not associated with any active drug
      application and were exploratory or hypothesis generating in nature. For training
      purposes, these reports were reviewed by the Nonclinical Pharmacogenomics
      Subcommittee consisting of the Center for Drug Evaluation and Research
      pharmacology and toxicology researchers and reviewers. In this article, we
      describe some of these submissions and report on our assessment of data content,
      format, and quality control metrics that were useful for evaluating these
      nonclinical genomics submissions, specifically in relation to the proposed
      MIAME/MINTox (minimum information about a microarray experiment/minimum
      information needed for a toxicology experiment) recommendations. These genomics
      submissions allowed both researchers and regulators to gain experience in the
      process of reviewing and analyzing toxicogenomics data. The experience will allow
      development of recommendations for the submission and review of these data as the
      state of the science evolves.

PMID- 16581547
TI  - Maternal genistein alters coat color and protects Avy mouse offspring from
      obesity by modifying the fetal epigenome.
AB  - Genistein, the major phytoestrogen in soy, is linked to diminished female
      reproductive performance and to cancer chemoprevention and decreased adipose
      deposition. Dietary genistein may also play a role in the decreased incidence of
      cancer in Asians compared with Westerners, as well as increased cancer incidence
      in Asians immigrating to the United States. Here, we report that maternal dietary
      genistein supplementation of mice during gestation, at levels comparable with
      humans consuming high-soy diets, shifted the coat color of heterozygous viable
      yellow agouti (A(vy/a) offspring toward pseudoagouti. This marked phenotypic
      change was significantly associated with increased methylation of six cytosine
      guanine sites in a retrotransposon upstream of the transcription start site of
      the Agouti gene. The extent of this DNA methylation was similar in endodermal,
      mesodermal, and ectodermal tissues, indicating that genistein acts during early
      embryonic development. Moreover, this genistein-induced hypermethylation
      persisted into adulthood, decreasing ectopic Agouti expression and protecting
      offspring from obesity. Thus, we provide the first evidence that in utero dietary
      genistein affects gene expression and alters susceptibility to obesity in
      adulthood by permanently altering the epigenome.

PMID- 16581549
TI  - The effect of chelation on blood pressure in lead-exposed children: a randomized
      study.
AB  - Studies in children suggest a weak association between blood lead concentration
      and blood pressure. To understand this better, we tested the strength of the
      association in children with elevated blood lead concentrations and whether
      succimer chelation changed blood pressure as it did blood lead. In a randomized
      clinical trial of 780 children with blood lead concentrations of 20-44 microg/dL
      at 12-33 months of age, we compared the systolic and diastolic blood pressure in
      the succimer-treated group and placebo group for up to 5 years of follow-up. We
      also analyzed the relation of blood lead to blood pressure. Children in the
      succimer group had lower blood lead concentrations for 9-10 months during and
      after treatment, but their blood pressure did not differ from those in the
      placebo group during this period. During 1-5 years of follow-up, children in the
      succimer group had systolic blood pressure 1.09 (95% confidence interval, 0.27
      1.90) mmHg higher than did untreated children in a model with repeated
      measurements, but the difference in diastolic blood pressure was not
      statistically significant. No association between blood lead and blood pressure
      was found. Overall, there is no association between blood lead and blood pressure
      in these children with moderately high lead exposure, nor does chelation with
      succimer change blood pressure.

PMID- 16581550
TI  - Renal and neurologic effects of cadmium, lead, mercury, and arsenic in children:
      evidence of early effects and multiple interactions at environmental exposure
      levels.
AB  - Lead, cadmium, mercury, and arsenic are common environmental pollutants in
      industrialized countries, but their combined impact on children's health is
      little known. We studied their effects on two main targets, the renal and
      dopaminergic systems, in > 800 children during a cross-sectional European survey.
      Control and exposed children were recruited from those living around historical
      nonferrous smelters in France, the Czech Republic, and Poland. Children provided
      blood and urine samples for the determination of the metals and sensitive renal
      or neurologic biomarkers. Serum concentrations of creatinine, cystatin C, and
      beta2-microglobulin were negatively correlated with blood lead levels (PbB),
      suggesting an early renal hyperfiltration that averaged 7% in the upper quartile
      of PbB levels (> 55 microg/L; mean, 78.4 microg/L). The urinary excretion of
      retinol-binding protein, Clara cell protein, and N-acetyl-beta-d-glucosaminidase
      was associated mainly with cadmium levels in blood or urine and with urinary
      mercury. All four metals influenced the dopaminergic markers serum prolactin and
      urinary homovanillic acid, with complex interactions brought to light. Heavy
      metals polluting the environment can cause subtle effects on children's renal and
      dopaminergic systems without clear evidence of a threshold, which reinforces the
      need to control and regulate potential sources of contamination by heavy metals.
      Key words: arsenic, biomarkers, cadmium, dopaminergic, heavy metals,
      interactions, lead, mercury, renal.

PMID- 16581551
TI  - Race, poverty, and potential exposure of middle-school students to air emissions
      from confined swine feeding operations.
AB  - Previous studies suggest that airborne effluent from swine confined animal
      feeding operations (CAFOs) may affect the health and quality of life of adults
      and the prevalence of asthma symptoms among children. To investigate the extent
      to which public school students may be exposed to airborne effluent from swine
      CAFOs and to evaluate the association between schools' demographic
      characteristics and swine CAFO exposures, we assessed the proximity of 226
      schools to the nearest swine CAFO and conducted a survey of school employees to
      identify schools with noticeable livestock odor. We used publicly available
      information describing the enrollment of each school to assess the association
      between race and socioeconomic status (SES) and swine CAFO exposure. Odor from
      livestock was noticeable outside (n = 47, 21%) and inside (n = 19, 8%) school
      buildings. Schools with < 63% enrollment of white students and > or = 47% of
      students receiving subsidized lunches at school were located closer to swine
      CAFOs (mean = 4.9 miles) than were the remaining schools (mean = 10.8 miles) and
      were more likely to be located within 3 miles of an operation than were schools
      with high-white/high-SES enrollment (prevalence ratio = 2.63; 95% confidence
      interval, 1.59-4.33). The prevalence of reported livestock odor varied with SES
      (low SES, 25%; high SES, 17%). These analyses indicate that the potential for in
      school exposure to pollution arising from swine CAFOs in North Carolina and the
      environmental health risks associated with such exposures vary according to the
      racial and economic characteristics of enrolled students.

PMID- 16581552
TI  - Association of in utero organochlorine pesticide exposure and fetal growth and
      length of gestation in an agricultural population.
AB  - From 1940 through the 1970s, organochlorine compounds were widely used as
      insecticides in the United States. Thereafter, their use was severely restricted
      after recognition of their persistence in the environment, their toxicity in
      animals, and their potential for endocrine disruption. Although substantial
      evidence exists for the fetal toxicity of organochlorines in animals, information
      on human reproductive effects is conflicting. We investigated whether infants'
      length of gestation, birth weight, and crown-heel length were associated with
      maternal serum levels of 11 different organochlorine pesticides: p,p 
      dichlorodiphenyltrichloroethane (p,p -DDT), p,p -dichlorodiphenyldichloroethylene
      (p,p -DDE), o,p -dichlorodiphenyltrichloroethane (o,p -DDT), hexachlorobenzene
      (HCB), gamma-hexachlorocyclohexane (gamma-HCCH), gamma-hexachlorocyclohexane
      (gamma-HCCH), dieldrin, heptachlor epoxide, oxychlordane, trans-nonachlor, and
      mirex. Our subjects were a birth cohort of 385 low-income Latinas living in the
      Salinas Valley, an agricultural community in California. We observed no adverse
      associations between maternal serum organochlorine levels and birth weight or
      crown-heel length. We found decreased length of gestation with increasing levels
      of lipid-adjusted HCB (adjusted gamma = -0.47 weeks; p = 0.05). We did not find
      reductions in gestational duration associated with any of the other
      organochlorine pesticides. Our finding of decreased length of gestation related
      to HCB does not seem to have had clinical implications for this population, given
      its relatively low rate of preterm delivery (6.5%).

PMID- 16581553
TI  - Urinary 1-hydroxypyrene as a biomarker of PAH exposure in 3-year-old Ukrainian
      children.
AB  - Urinary 1-hydroxypyrene (1-OHP) is a biomarker of polycyclic aromatic hydrocarbon
      (PAH) exposure. We measured urinary 1-OHP in 48 children 3 years of age in
      Mariupol, Ukraine, who lived near a steel mill and coking facility and compared
      these with 1-OHP concentrations measured in 42 children of the same age living in
      the capital city of Kiev, Ukraine. Children living in Mariupol had significantly
      higher urinary 1-OHP and creatinine-adjusted urinary 1-OHP than did children
      living in Kiev (adjusted: 0.69 vs. 0.34 micromol/mol creatinine, p < 0.001;
      unadjusted: 0.42 vs. 0.30 ng/mL, p = 0.002). Combined, children in both cities
      exposed to environmental tobacco smoke in their homes had higher 1-OHP than did
      children not exposed (0.61 vs. 0.42 micromol/mol creatinine; p = 0.04; p = 0.07
      after adjusting for city). In addition, no significant differences were seen with
      sex of the children. Our sample of children in Mariupol has the highest reported
      mean urinary 1-OHP concentrations in children studied to date, most likely due to
      their proximity to a large industrial point source of PAHs.

PMID- 16581554
TI  - Airborne endotoxin is associated with respiratory illness in the first 2 years of
      life.
AB  - To determine the influence of endotoxin on the incidence of acute respiratory
      illness during the first 2 years of life, we carried out a longitudinal follow-up
      study, beginning at birth, of 332 children born in Prince Edward Island, Canada.
      We measured 5-day averaged air endotoxin in the homes of children, whose parents
      provided information by daily symptom diaries and twice-monthly telephone contact
      for up to 2 years. Endotoxin concentration was 0.49 +/- 3.49 EU/m3 (geometric
      mean +/- geometric SD), and number of annualized illness episodes was 6.83 +/-
      2.80 (mean +/- SD). A doubling of the air endotoxin concentration was associated
      with an increase of 0.32 illness episodes per year (p = 0.0003), adjusted for
      age, year of study, breast-feeding, environmental tobacco smoke, child care
      attendance, indoor temperature, and income. Indoor mold surface area and fungal
      ergosterol were not significantly associated with endotoxin. Airborne endotoxin
      appears to be a risk factor for clinically symptomatic respiratory illnesses
      during the first 2 years of life independent of indoor fungus.

PMID- 16581555
TI  - Induction of asthma and the environment: what we know and need to know.
AB  - The prevalence of asthma has increased dramatically over the last 25 years in the
      United States and in other nations as a result of ill-defined changes in living
      conditions in modern society. On 18 and 19 October 2004 the U.S. Environmental
      Protection Agency and the National Institute of Environmental Health Sciences
      sponsored the workshop "Environmental Influences on the Induction and Incidence
      of Asthma" to review current scientific evidence with respect to factors that may
      contribute to the induction of asthma. Participants addressed two broad
      questions: a) What does the science suggest that regulatory and public health
      agencies could do now to reduce the incidence of asthma? and b) What research is
      needed to improve our understanding of the factors that contribute to the
      induction of asthma and our ability to manage this problem? In this article (one
      of four articles resulting from the workshop), we briefly characterize asthma and
      its public health and economic impacts, and intervention strategies that have
      been successfully used to prevent induction of asthma in the workplace. We
      conclude with the findings of seven working groups that focus on ambient air,
      indoor pollutants (biologics), occupational exposures, early life stages, older
      adults, intrinsic susceptibility, and lifestyle. These groups found strong
      scientific support for public health efforts to limit in utero and postnatal
      exposure to cigarette smoke. However, with respect to other potential types of
      interventions, participants noted many scientific questions, which are summarized
      in this article. Research to address these questions could have a significant
      public health and economic impact that would be well worth the investment.

PMID- 16581557
TI  - How exposure to environmental tobacco smoke, outdoor air pollutants, and
      increased pollen burdens influences the incidence of asthma.
AB  - Asthma is a multifactorial airway disease that arises from a relatively common
      genetic background interphased with exposures to allergens and airborne
      irritants. The rapid rise in asthma over the past three decades in Western
      societies has been attributed to numerous diverse factors, including increased
      awareness of the disease, altered lifestyle and activity patterns, and ill
      defined changes in environmental exposures. It is well accepted that persons with
      asthma are more sensitive than persons without asthma to air pollutants such as
      cigarette smoke, traffic emissions, and photochemical smog components. It has
      also been demonstrated that exposure to a mix of allergens and irritants can at
      times promote the development phase (induction) of the disease. Experimental
      evidence suggests that complex organic molecules from diesel exhaust may act as
      allergic adjuvants through the production of oxidative stress in airway cells. It
      also seems that climate change is increasing the abundance of aeroallergens such
      as pollen, which may result in greater incidence or severity of allergic
      diseases. In this review we illustrate how environmental tobacco smoke, outdoor
      air pollution, and climate change may act as environmental risk factors for the
      development of asthma and provide mechanistic explanations for how some of these
      effects can occur.

PMID- 16581556
TI  - How exposures to biologics influence the induction and incidence of asthma.
AB  - A number of environmental factors can affect the development and severity of
      allergy and asthma; however, it can be argued that the most significant inhaled
      agents that modulate the development of these conditions are biologics.
      Sensitization to environmental allergens is an important risk factor for the
      development of asthma. Innate immune responses are often mediated by receptors on
      mononuclear cells whose primary ligands arise from microorganisms. Many
      pathogens, especially viruses, target epithelial cells and affect the host immune
      response to those pathogens. The acquired immune response to an allergen is
      influenced by the nature of the innate immune system. Products of innate immune
      responses to microbes promote T(H)1-acquired responses. In the absence of T(H)1
      responses, T(H)2 responses can dominate. Central to T(H)1/T(H)2 balance is the
      composition of contaminants that derive from microbes. In this review we examine
      the biology of the response to allergens, viruses, and bacterial products in the
      context of the development of allergy and asthma.

PMID- 16581559
TI  - Cytokines in atopic diseases: revisiting the Th2 dogma.
AB  - In the field of allergic diseases, extensive research has demonstrated the
      implication of a strong TH2 activation that both initiates and maintains in situ
      inflammation with the help of TH2 cytokines. However, as anti-TH2 cytokines
      therapy is not sufficient to suppress the disease, a more complex immunological
      mechanism is suspected. In this review, we will revisit the TH2 dogma in allergic
      diseases, propose a possible implication of TH1 inflammation correlated with the
      severity of atopic disease, to conclude with the therapeutic solutions envisaged.

PMID- 16581560
TI  - Clinical classification of vasculitis.
AB  - Clinical classification of vasculitis is needed to facilitate diagnosis and
      management of the disease as well as to assign patients to defined groups for
      clinical studies. Caliber and size of the vessels predominantly involved strongly
      influence the clinical features of the different forms of vasculitis and
      therefore are one major criterion for classification. As such, panarteritis
      nodosa involves medium-sized vessels and presents on the skin with subcutaneous
      nodules and livedo racemosa, while it does not cause glomerulonephritis.
      Leukocytoclastic vasculitis (LcV) involves the small vessels, resulting in
      palpable purpura, and sometimes also in glomerulonephritis. The classification
      systems of the American College of Rheumatology (ACR) and of the Chapel Hill
      Consensus Conference (CHCC) have gained wide acceptance. Yet, they need to be
      updated, especially with regard to LcV, the most common vasculitis of the skin.
      Here distinctions must be made for prognostic, diagnostic and therapeutic reasons
      between IgG/IgM- and IgA-associated LcV (Henoch-Schoenlein purpura, HSP), as well
      as between HSP of children and HSP of adult age. The latter bears the highest,
      while IgG/IgM-associated LcV bears the lowest risk for complications. This update
      on the clinical classification of vaculitis is based on the ACR and CHCC system
      and focuses on those forms which regularly cause cutaneous symptoms. It provides
      a survey on the vasculitic syndromes and should help in deciding when i)
      extensive diagnostic procedures are needed in patients with LcV, ii) therapy
      should be less or more aggressive, e.g. in cutaneous versus systemic PAN, iii)
      therapy should be promptly initiated, e.g. when any form of severe, ANCA
      associated vasculitis is suspected.

PMID- 16581561
TI  - The contribution of keratinocytes to the pathogenesis of atopic dermatitis.
AB  - Atopic dermatitis (AD) develops from a complex interplay between environmental,
      genetic, immunologic and biochemical factors. Relevant to the amplification and
      persistence of inflammatory and immune responses in AD skin are keratinocytes,
      which can be induced to secrete proinflammatory mediators in response to a
      variety of stimuli, including epidermal barrier perturbation. Moreover,
      keratinocytes from AD patients synthesize exaggerated amounts of mediators (e.g.,
      GM-CSF and RANTES/CCL5) important for enhanced recruitment as well as sustained
      survival and activation of T cells and dendritic cells. AD keratinocytes have a
      constitutive dysregulated activity of transcription factors that modulate the
      expression of inflammatory genes, suggesting the existence of predetermined
      mechanisms targeting atopic inflammation to the skin. Among these, the existence
      of a defective epidermal barrier, which appears related to decreased ceramide
      generation and abnormal degradation of corneodesmosomes, certainly plays a
      central role in the predisposition to AD.

PMID- 16581558
TI  - A brief targeted review of susceptibility factors, environmental exposures,
      asthma incidence, and recommendations for future asthma incidence research.
AB  - Relative to research on effects of environmental exposures on exacerbation of
      existing asthma, little research on incident asthma and environmental exposures
      has been conducted. However, this research is needed to better devise strategies
      for the prevention of asthma. The U.S. Environmental Protection Agency (EPA) and
      National Institute of Environmental Health Sciences held a conference in October
      2004 to collaboratively discuss a future research agenda in this area. The first
      three articles in this mini-monograph summarize the discussion on potential
      putative environmental exposure; they include an overview of asthma and
      conclusions of the workshop participants with respect to public health actions
      that could currently be applied to the problem and research needs to better
      understand and control the induction and incidence of asthma, the potential role
      of indoor/outdoor air pollutants in the induction of asthma), and biologics in
      the induction of asthma. Susceptibility is a key concept in the U.S. EPA "Asthma
      Research Strategy" document and is associated with the U.S. EPA framework of
      protecting vulnerable populations from potentially harmful environmental
      exposures. Genetics, age, and lifestyle (obesity, diet) are major susceptibility
      factors in the induction of asthma and can interact with environmental exposures
      either synergistically or antagonistically. Therefore, in this fourth and last
      article we consider a number of "susceptibility factors" that potentially
      influence the asthmatic response to environmental exposures and propose a
      framework for developing research hypotheses regarding the effects of
      environmental exposures on asthma incidence and induction.

PMID- 16581562
TI  - Epidermolysis Bullosa Simplex with mottled pigmentation: mutation analysis in the
      first reported Hispanic pedigree with the largest single generation of affected
      individuals to date.
AB  - Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP), characterized
      by trauma-induced blisters, distinct pigmentary changes of the trunk and
      extremities, and acral hyperkeratotic papules, is almost exclusively caused by a
      common KRT5 missense mutation affecting the V1 region of keratin 5. We studied
      the first Hispanic family, the largest single generation of affected family
      members in which 5 out of 10 siblings inherited EBS-MP from their affected
      father, as well a second large pedigree, the first reported of Finnish ancestry.
      In both families, the heterozygous transition mutation 74C-->T of the keratin 5
      gene, which results in amino acid substitution P25L, completely co-segregated
      with the EBS-MP phenotype.

PMID- 16581563
TI  - Study of housekeeping gene expression in human keratinocytes using OLISA, a long
      oligonucleotide microarray and q RT-PCR.
AB  - In recent years, applications of microarray platforms have been extended to
      different areas of research including cosmetic and pharmaceutical. Although
      microarray technology is still improving its sensitivity and flexibility,
      researchers often turn toward quantitative RT-PCR for data validation. Assessment
      of messenger RNA quantity by these methods is based on comparison with internal
      standard genes, mainly housekeeping genes, so called because their synthesis
      occurs normally at a constant level. However, numerous studies showed that
      expression of these genes could vary in given situations. Here, we report results
      on four housekeeping genes (GAPDH, beta-2 microglobulin, S40 and S26 ribosomal
      sub-units) with constant expression levels established on OLISA microarray using
      different keratinocyte cultures. Moreover, qRT-PCR validation demonstrates that
      S26 ribosomal is a good housekeeping gene on keratinocytes and skin studies. Our
      data indicate that S26 gene can be routinely used to standardize results to
      investigate differentially expressed genes in a healthy human skin.

PMID- 16581564
TI  - Interferon-gamma-induced 15-lipoxygenase-2 expression in normal human epidermal
      keratinocytes and a pathogenic link to psoriasis vulgaris.
AB  - Epidermal keratinocytes contain 15-lipoxygenase, which generates 15
      hydroxyeicosatetraenoic acid, a major metabolite of arachidonic acid. Although
      two isozymes, 15-lipoxygenase-1 and -2, exist, it remains unclear which isozyme
      plays an important role in inflammatory processes and proliferative skin
      diseases. In the present study, we demonstrated that 15-lipoxygenase-2 expression
      was increased in normal human epidermal keratinocytes and HaCaT cells treated
      with interferon-gamma (200 U/ml), while no induction of 15-lipoxygenase-1 was
      observed. Under the same culture conditions, no 15-lipoxygenase-2 was expressed
      by a carcinoma cell line, A431. Weak expression of 15-lipoxygenase-2 was observed
      in the basal cell layer of non-lesional psoriatic skin by in situ hybridization
      and immunostaining, whereas strong expression of 15-lipoxygenase-2 was observed
      in all living layers of psoriatic lesions. Actinic keratosis and squamous cell
      carcinomas showed a variable immunostaining pattern for 15-lipoxygenase-2. These
      results indicate that 15-lipoxygenase-2 is implicated in interferon-gamma-induced
      inflammatory processes in normal human epidermal keratinocytes and psoriatic
      skin.

PMID- 16581565
TI  - Histopathologic and direct immunofluorescence findings of the papulopustular
      lesions in Behcet's disease.
AB  - Although papulopustular lesions are common in patients with Behcet's disease
      (BD), clinically they may not be differentiated from other diseases with
      papulopustular presentation such as acne vulgaris or folliculitis. Therefore,
      there is disagreement as to whether they should be used as a diagnostic criterion
      in BD. The aim of this study was to determine whether the histopathologic
      evaluation of the papulopustular lesions may assist in the diagnosis of BD.
      Eighteen patients with BD and 16 control patients consisting of eleven patients
      with bacterial folliculitis and five patients with acne vulgaris were included in
      the study. After the detailed histopathologic evaluation by two pathologists who
      were blinded to the clinical diagnoses, the histopathologic findings were
      classified into three patterns as follows; pattern I: vasculitis (lymphocytic or
      leucocytoclastic); pattern II: folliculitis and/or perifolliculitis; pattern III:
      superficial and/or deep perivascular, and/or interstitial dermatitis. In
      addition, direct immunofluorescence studies were performed in order to evaluate
      the deposition of IgM, IgG, IgA, C3, or fibrinogen in dermal blood vessels. 27.8%
      of the patients with BD (5 patients) revealed lymphocytic vasculitis, while none
      of the control group did; and the difference was found statistically significant
      (P=0.046). The rate of pattern II which included folliculitis and/or
      perifolliculitis was 50.0% in control patients and 16.7% in the patients with BD;
      and the difference was found statistically significant (P=0.038). No difference
      was found between the two groups with regard to pattern III or direct
      immunofluorescence findings (P>0.05). Our results indicate that only vasculitic
      changes can be useful when histopathological features of papulopustular lesions
      are to be employed as a diagnostic criterion in patients with suspected BD.

PMID- 16581567
TI  - Methotrexate for the treatment of adult atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease mediated by
      allergen-specific T cells which are recruited and activated in lesional skin.
      Methotrexate (MTX) is an old systemic agent used at low dosage for the treatment
      of psoriasis, another T cell-mediated skin disorder. Since MTX has been shown to
      improve the clinical symptoms of eczema in a model of antigen-specific dermatitis
      in mice, we postulated that it could be an effective treatment of AD. In the
      present open retrospective study, we report our results on the treatment of
      moderate to severe AD by MTX. Twenty patients (17 to 68-years-old) with low
      responses to routine therapies were treated (three months to 2 1/2 years) with a
      weekly dose of MTX ranging from 7.5 to 25 mg. The evaluation was made on
      physician's global assessment after 3 months of MTX use, and showed that 75%
      (15/20) of patients improved after 3 months of MTX use, among which 13/20 with an
      improvement>70%. The beginning of improvement was observed between the fourth and
      the eighth week after MTX was initiated. Tolerance was good. However, nausea and
      increase of liver enzymes were observed in 5 patients and required
      discontinuation of MTX in 2 patients. In conclusion, MTX seems to be an effective
      and safe treatment of AD. Placebo-controlled clinical trials are needed to
      confirm our observations and to define more precisely the effectiveness and
      safety of MTX in adult AD.

PMID- 16581566
TI  - Can atopy patch tests with aeroallergens be an additional diagnostic criterion
      for atopic dermatitis?
AB  - The complex pathomechanisms underlying skin lesions in atopic dermatitis (AD)
      result in variations of the clinical picture and frequent diagnostic
      difficulties. The purpose of this study was to evaluate the usefulness of atopy
      patch tests (APT) for aeroallergens in the diagnosis of AD. The study involved
      115 adult patients with AD and 98 healthy volunteers (the control group). APTs
      for cat dander allergens, birch pollen, a mixture of house dust mite species and
      a mixture of 5 grass pollen allergens were applied for both groups. Positive
      reaction to at least one test allergen was found in 53.9% patients compared to
      6.2% in the control group (p<0.001). The most frequent hypersensitivity (45.2%)
      observed was to house dust mite allergens. Polyvalent allergy to 2-4 allergens
      was found in 56.5% patients. The specificity of tests exceeded 75%, whereas the
      sensitivity varied from 18 to 66%. CONCLUSIONS: 1. Atopy patch tests, which are
      characterised by considerable specificity, confirm the role of polyvalent contact
      hypersensitivity to aeroallergens in the development of atopic dermatitis. 2.
      Positive aeroallergen ATP results are observed in the majority of patients and
      can thus be regarded as an additional diagnostic criterion in atopic dermatitis.

PMID- 16581568
TI  - Livedoid vasculopathy. The role of hyperhomocysteinemia and its simple
      therapeutic consequences.
AB  - Livedoid vasculopathy (LV) is characterized by localized painful ulcers, livedo
      reticularis and atrophie blanche. LV is considered as an occlusive vasculopathy
      due to a hypercoagulable state. Hyperhomocysteinemia is a prothrombotic
      condition, which has as yet received little attention in this context. We report
      a 49-year-old woman with livedoid vasculopathy. The patient presented with an
      elevated homocysteine level caused by renal insufficiency, vitamin-B6 deficiency
      and reduced vitamin-B12 concentration. We treated her with low-molecular heparin
      and pentoxifylline. Folic acid, vitamin B6 and B12 were substituted for therapy
      of hyperhomocysteinemia. Substitution therapy led to a reduction of homocysteine
      levels. Under the complex therapy the ulcers healed without recurrence within 16
      months. Thrombophilia is of pathogenetic importance in LV. Hyperhomocysteinemia
      may be another cause of hypercoagulability. Substitution of folic acid, vitamins
      B12 and B6 (cofactors of homocysteine metabolism) is an effective treatment of
      hyperhomocysteinemia and thus hypercoagulability can be causally treated.

PMID- 16581569
TI  - Elastosis colloidalis conglomerata (adult colloid milium, paracolloid of the
      skin): a maximal manifestation of actinic elastosis?
AB  - We report the case of a 50-year-old woman with multiple soft papules in the
      perioral region resistant to local corticosteroid and antibiotic therapies.
      Histology revealed elastosis colloidalis conglomerata. There were no hints for a
      deposition disease. The patient was treated with local retinoids. We report on
      the therapeutic outcome.

PMID- 16581571
TI  - Improvement of sun-related knowledge and protection practice.
AB  - The aim of this study was to examine changes in sun-related knowledge and sun
      protection practice among Greek mothers and children during 1993-2002. A total of
      315 mothers in 1993 and 295 mothers in 2002, with their 649 and 491 children
      respectively, were randomly selected to answer the same questionnaire on sun
      related issues. Sun knowledge and protection practice were determined by an index
      score. Significantly more mothers in 2002 compared to 1993 had 'good' (58.9%
      versus 16%) and 'excellent' levels (28% versus 6%) of sun knowledge (p<0.001). In
      2002, 40% of the mothers and children (versus 27% and 30% each in 1993) had
      'good' levels of sun protection practice, while 28% of the mothers and 26% of the
      children (versus none in 1993) reported 'excellent' levels (p<0.001). Knowledge
      and sun protection practice were significantly improved, probably due to an
      information campaign conducted between both surveys.

PMID- 16581570
TI  - Psoriasis: severity assessment in clinical practice. Conclusions from workshop
      discussions and a prospective multicentre survey of psoriasis severity.
AB  - Psoriasis treatment is highly individualized. Although a standardized assessment
      of psoriasis severity for clinical practice may be theoretically advantageous for
      the purposes of determining treatment, the relevance of currently available
      research tools in clinical practice is uncertain. Our objectives were to
      ascertain in workshop discussions and through a prospective survey the relevance
      of standard severity measures in clinical practice with regard to choice of
      treatment. Although there was agreement on the possible structure of an algorithm
      for the treatment-related definition of psoriasis severity, consensus on the cut
      off levels for the PASI and %BSA that would indicate a switch in treatment mode
      could not be reached. The lack of agreement prompted a prospective survey of 112
      patients with psoriasis from 10 countries. This survey used a formal
      questionnaire asking for the PASI and %BSA scores, the patient's self assessment
      score (VAS ranging from 0 to 10), location of the psoriatic lesions and disease
      phase. Severity scores from 20 patients pre-selected for inclusion in a trial of
      a biological agent were included for comparison. Severity scores were analysed in
      relation to the choice of treatment (topical or systemic, which included
      phototherapy and combination) suggested by the treating physician.PASI scores
      differed significantly between the treatment groups (topical vs systemic,
      p=0.009); however, there was large overlap in the range of PASI scores between
      the groups. The same was true for VAS scores (topical vs systemic, p=0.035). %BSA
      scores were not significantly different between treatment groups. There was a
      large overlap for both the topical and systemic treatment groups with the
      biologicals group for the range of both the PASI and %BSA scores. A standardized
      protocol for the evaluation of psoriasis severity based on established severity
      scores (PASI, %BSA) appears to be unrealistic in day-to-day clinical practice. In
      clinical practice, a host of factors must be evaluated alongside possible metric
      measures. This requires experience and the specialized medical education of those
      involved in the treatment of patients with psoriasis.

PMID- 16581572
TI  - Ano-rectal lymphogranuloma venereum: 22 cases reported in a sexually transmited
      infections center in Paris.
AB  - In January 2004 the European Surveillance of Sexually Transmitted Infections
      Network (ESSTI) issued an international alert regarding an outbreak of
      Lymphogranuloma venereum (LGV) in Rotterdam in a sexual network of men who have
      sex with men (MSM). Further to this alert, a retrospective survey was set up by
      the Institut de Veille Sanitaire and the reference laboratories for N.gonorrhoeae
      and Chlamydia in France. Our STI clinic in Paris carried out a clinico-biological
      retrospective study involving 154 MSM screened for anorectal sexually transmitted
      infections (STIs) between January 2002 and May 2004 and a prospective study
      between May 2004 and August 2004. Out of 216 swabs of rectal discharge from
      homosexual or bisexual males, a total of 32 were positive for C. trachomatis
      (14.8%) (3 patients in 2002, 11 in 2003 and 18 in 2004). C. trachomatis-positive
      rectal strains were genotyped to detect the specific C. trachomatis serovars and
      revealed serovars L(2) for 22 patients (respectively 1 in 2002, 9 in 2003 and 12
      in 2004). Serum antibody titers for Chlamydia trachomatis were determined among
      14 subjects and revealed strongly positive in 13 cases (1/512 to 1/16384) titers
      of IgG. These 22 patients with clinico-biologically confirmed anorectal
      lymphogranuloma venereum (ARLGV) were all homosexual men. They ranged from 28 to
      52 years (mean age 39.2 years). 12 of 21 (57.1%) subjects with an ARLGV diagnosis
      were seropositive for human immunodeficiency virus (HIV) (one not done). Although
      rare, anorectal lymphogranuloma venereum (ARLGV) still exists in France and
      should not be forgotten in the differential diagnosis of rectal problems in male
      homosexuals.

PMID- 16581573
TI  - Congenital myofibromatosis in two siblings.
AB  - Infantile myofibromatosis (IM) is a rare mesenchymal disorder characterized by
      solitary or multiple nodules involving the skin, striated muscles, bones and,
      sometimes, viscera. Although most cases are sporadic, there have been a few
      reports of a familial pattern of inheritance. In most cases, diagnosing IM is not
      difficult. However, IM should be differentiated from neurofibromatosis,
      paediatric sarcomas, nodular fasciitis, fibrous hamartoma of infancy, and hyaline
      juvenile fibromatosis. The prognosis for IM depends on the degree of visceral
      involvement. Since spontaneous tumoral regression is usual, in cases of limited
      involvement therapeutic abstention and patient observation are recommended.
      Surgery, chemotherapy or radiotherapy are reserved for patients with multiple
      visceral localizations, particularly in the lung and gastrointestinal tract,
      which may have a worse prognosis and potentially fatal outcome. We report on a
      family in which two siblings, born from non-consanguineous parents, were affected
      by congenital myofibromatosis. In both patients, tumors were present at birth,
      with multicentric subcutaneous, muscular, skeletal and visceral involvement. The
      growing subcutaneous myofibromas were surgically removed, while the smallest ones
      disappeared spontaneously over the course of 24 months.

PMID- 16581574
TI  - Bullous prurigo pigmentosa.
AB  - Prurigo pigmentosa is a rare inflammatory skin disease of unknown etiology,
      characterized by recurrent, symmetrical, pruritic, erythematous papules resulting
      in gross reticular hyperpigmentation. The rash occurs mainly on the back, the
      chest and the nape of the neck. While PP is observed rather frequently in Japan,
      only a few cases have come to notice in other countries. Vesicular or bullous
      forms have been reported only rarely. The differential diagnosis includes lichen
      pigmentosus, pigmented contact dermatitis, confluent and reticulated
      papillomatosis of Gougerot and Carteaud, dermatitis herpetiformis and bullous
      lichen ruber planus. This case report concerns a young Caucasian patient with
      prurigo pigmentosa, in whom predominantly vesicular, but also bullous
      manifestations appeared on an existing maculopapular eruption on the trunk.

PMID- 16581575
TI  - Squamous cell carcinoma of the eyelid arising from palpebral conjunctiva.
AB  - We reported a 58-year-old Japanese man with squamous cell carcinoma (SCC) of the
      left upper eyelid arising from the palpebral conjunctiva. The tumor had been
      incised by a former doctor under the diagnosis of chalazion. Histopathological
      examination of the relapsed tumor revealed atypical squamous cells invading
      towards the eyelid skin from the epithelium of palpebral conjunctiva. We
      performed a total resection of the tumor and reconstructed the upper eyelid by
      the technique of Mustarde's switch flap. During 10 months of follow-up, neither
      local recurrence nor metastasis has been detected and the reconstructed eyelids
      showed good course in function and in appearance. SCC of the palpebral
      conjunctiva is quite rare, however, it often resembles chronic conjunctivitis or
      chalazion. It is important to consider the possibility of SCC in addition to
      sebaceous carcinoma when we see a patient with an eyelid lesion, even one which
      looks like a benign condition such as chronic conjunctivitis or chalazion.

PMID- 16581576
TI  - Polymorphic cutaneous rhinosporidiosis.
AB  - Rhinosporidiosis is a chronic granulomatous condition caused by Rhinosporidium
      seeberi primarily affecting the mucosa of the nose, eyes and sinuses. The
      patients usually present with nasal symptoms and skin involvement is uncommon [1
      3]. Here, a patient with nasal rhinosporidiosis having two different
      morphological types of cutaneous lesions of rhinosporidiosis, coexisting at the
      same time and at the same site, is reported. The diagnosis was confirmed by FNAC
      (Fine Needle Aspiration Cytology) and skin biopsy from the skin lesions. To the
      best of my knowledge, such an unusual occurrence has not been reported earlier in
      literature.

PMID- 16581577
TI  - Transient zinc deficiency in a breast fed, premature infant.
AB  - A 5-month-old-male was observed for an acrodermatitis enteropathica-like skin
      eruption evolving since the second month. He was born prematurely at 27 weeks and
      his neonatal course was complicated by respiratory distress syndrome, sepsis and
      subependimary haemorrhage. He was fed with breast milk from the second day of
      life, fortified initially by a protein mineral supplement containing zinc. Serum
      zinc concentration was low and the mother's serum and milk had normal zinc
      values. Oral zinc supplementation was introduced with total clearing after three
      weeks. Treatment lasted 22 months and no relapse was observed after
      discontinuation. Premature infants have a negative zinc balance mainly secondary
      to inadequate stores and high requirements. The relevance of these factors is
      illustrated by the present case where symptomatic zinc deficiency developed
      despite maternal milk with normal zinc content and a milk fortifier containing
      zinc.

PMID- 16581578
TI  - Interpretative enactments and the analytic setting.

PMID- 16581579
TI  - Being a psychoanalyst: an everyday audacity.
AB  - This paper is the work of five psychoanalysts who came together as a group in
      order to reflect on their work as analysts. How are we analysts to identify the
      unconscious resistances that may sometimes hold us back from offering
      psychoanalysis to some patients? Do these resistances sometimes hamper the inner
      freedom that we require in order to maintain a psychoanalytic focus once that
      process is under way? How do we manage from time to time to overcome these
      resistances or, better, make use of them in order to develop our understanding of
      the unconscious dynamics that create the link between analyst and patient? The
      authors discuss these issues with particular reference to clinical situations
      taken from classic psychoanalytic treatment cases during which the analyst had to
      find within him- or herself the audacity to be a psychoanalyst. Each clinical
      situation is different: preliminary interviews, in the course of the actual
      treatment, issues that emerge in the training of candidates. One of the
      significant features of this group lies in the fact that the participants are at
      different stages in their development as psychoanalysts (student, associate
      member, full member, training analyst). This means that their experiences
      complement one another and encourage a discussion of issues such as how
      psychoanalysis can be passed on, and the relationship between supervisor and
      supervisee.

PMID- 16581580
TI  - Analytic impasse and the third: clinical implications of intersubjectivity
      theory.
AB  - The author examines the notion of the third within contemporary intersubjectivity
      theory. He utilizes a variety of metaphors (the triangle, the seesaw, strange
      attractors, and the compass) in an effort to explain this often misunderstood
      concept in a clear and readily usable manner. An argument is made to the effect
      that intersubjectivity theory has direct implications for clinical practice, and
      that the notion of the third is particularly useful in understanding what happens
      in and in resolving clinical impasses and stalemates. Specifically, the author
      suggests that certain forms of self-disclosure are best understood as attempts to
      create a third point of reference, thus opening up psychic space for self
      reflection and mentalization. He provides a clinical case as well as a number of
      briefer vignettes to illustrate the theoretical concepts and to suggest specific
      modifications of the psychoanalyst's stance that give the patient greater access
      to the inner workings of the analyst's mind. This introduces a third that
      facilitates the gradual transformation from relations of complementarity to
      relations of mutuality.

PMID- 16581581
TI  - Aspects of a compliant container: considering narcissistic personality
      configurations.
AB  - Attempts to expand Bion's container-contained model and to use it as an
      instrument for investigating psychic disorders arising in the analytical context
      have led the author to conjecture about the model's dynamics. In this paper, she
      illustrates a hypothetical compliant container by clinical material, in order to
      describe a psychic structure that contains only what is pleasant, only that which
      does not cause conflict or pain. Through a dynamic of ideal accommodation, a
      compliant container makes any disagreements, contradictions, limits and
      differences disappear, recognizing only what is very familiar and commonplace.
      The results are misleading, pseudological thoughts and concepts founded on
      strategic plans to maintain a narcissistic defensive system.

PMID- 16581582
TI  - On the psychodynamics of collecting.
AB  - The urge to collect is a ubiquitous phenomenon which has anthropological,
      sociobiological and individual psychodynamic roots, but occurs far more
      frequently among men than women. The author examines the reasons for this gender
      difference and defines systematic collecting to distinguish it from addictive,
      obsessive and messy collecting, and from related phenomena such as perversion.
      The mode of collecting and choice of object are important indicators as to the
      unconscious psychodynamics of a collector and offer opportunity to describe his
      structural level. Collecting ranges across a broad spectrum, from an ego-syntonic
      integrated mode, i.e. sublimation, to a neurotic defence against pre-oedipal or
      oedipal traumas and conflicts. Alongside this drive-theoretical approach, object
      and Kleinian theory are also applied to the understanding of collecting.
      Collecting represents a specific form of object relating and way of handling
      primary loss trauma, which is different from addiction, compulsion, or
      perversion. Under certain circumstances collecting can also result in a
      successful Gestalt or way of life. The paper concludes with a case study showing
      how collecting develops from a pre-oedipal to a more integrated oedipal mode
      during the course of the analysis, which is reflected in changes in the
      transference.

PMID- 16581583
TI  - The clinical concept of analytic process: a conceptual investigation.
AB  - The authors discuss the term 'analytic process', confirming the variability of
      the meanings ascribed to it. Although all the psychoanalysts of this and previous
      times acknowledge the existence of something called analytic process, as well as
      its importance, it has not been possible up to now to establish a consensual
      definition of it. The definitions are not only numberless, they also contradict
      one another. The possible advantages to analytic theory and practice proceeding
      from a uniform concept are incontrovertible. A review of the subject in the
      psychoanalytic literature has been performed. A conceptual study concerning the
      term, carried out among members of a psychoanalytic society affiliated to the IPA
      is presented, no consensual conceptualization for the term analytic process
      having been found. The subjects referred to the term as deriving from a variety
      of elements, some in common, but there was no agreement regarding the elements
      themselves. There was consensus regarding the role of the analytical relationship
      in the process, considered fundamental, as well as that of the extent to which
      the individual life experiences in that relationship de?ne the unique character
      acquired by the process within it.

PMID- 16581584
TI  - The impulse to infidelity and oedipal splitting.
AB  - Freud suggested that the child perceives parental intercourse as an act of
      infidelity by the desired but unfaithful parent. Parental sexual infidelity is
      felt to be a major narcissistic injury that gives rise to fantasies of revenge. A
      defensive organization arises to manage this trauma and its attendant revenge
      fantasies. That organization involves splitting of the desired parent into
      faithful and unfaithful parts, displacement of hostility on to the rival parent,
      and identification with the desired but unfaithful parent resulting in the
      impulse to infidelity. Romantic fantasies of escape and rescue from evil rivals
      provide guilt free ways of satisfying fantasies of oedipal revenge. In those
      fantasies the evil rival is turned into an injured third party who gets his or
      her just deserts as the romantic couple gets to live happily ever after. This
      defensive organization may embroil patients in complicated love triangles as
      adults for which they may seek treatment. Analyzing the repudiated narcissistic
      wound of parental infidelity and the disguised revenge fantasies that defend
      against that wound may provoke narcissistic rage towards the analyst as a
      moralistic, possessive, controlling, envious, and spoiling oedipal parent.

PMID- 16581585
TI  - Self, other and dialogical space in autistic disorders.
AB  - The authors propose to re-evaluate Tustin's thesis using both the extensive
      clinical material of a child with an autistic disorder [PDD], and current
      research on infant development. Beebe's concept of 'interaction structure' that
      could be inferred from the fifth month of life using face-to-face research data
      is used for postulating a dialogic space that would be generated inside such
      structure, allowing for definition of self and other in a relationship. If such
      space is collapsed, the other would be a threat of annihilation for the self,
      thus it should be avoided or merged with, which could explain the systematic
      avoidance of the not-me in autistic states. The authors stress that these ideas
      are just one alternate model, among several, that seems to be able to explain the
      patient's deviant development.

PMID- 16581586
TI  - Reflections on the setting in the treatment of adolescents.
AB  - The author focuses on the significance of the setting for the development of the
      psychoanalytic process, especially in the case of adolescents who request
      analytic treatment. Her main goals are to specify: a) how the setting is
      configured with this type of patients; and b) to what extent it contributes to
      the creation of an inner space that may internalize a figure with reverie--a good
      object that will metabolize the bad and thus enable identification. The setting,
      which is considered the necessary context for analytic work, is defined as
      bearing two facets: that of the analyst, which must be constant and stable, and
      that of the adolescent, which will progressively change provided that the analyst
      maintains a firm context that contributes to make the adolescent feel contained
      and accepted. It is such a feeling that will enable the unfolding of the analytic
      process. The author emphasizes the importance of the presence of the analyst (his
      or her voice, the manner of his or her speech, and so on), and the need for the
      analyst to comply with the rules he or she has established together with the
      patient. She presents a clinical case to illustrate this conceptualization.

PMID- 16581587
TI  - My life is a longing: child abuse and its adult sequelae. Results of the Brody
      longitudinal study from birth to age 30.
AB  - The psychoanalytically oriented Brody longitudinal study has followed the
      psychological development of 76 individuals from birth to age 30. Ten suffered
      severe maltreatment in childhood in the form of rejection and/or physical abuse
      at the hands of one or both parents. This report describes the effects of child
      abuse on the emerging personalities of the children, as well as on their adult
      personalities and mental health. Specifically, as adults the maltreated children
      had significantly more psychiatric illness (typically depressions and anxiety
      disorders), less mature psychological defense mechanisms, more insecure mental
      representations of attachment to their parents as indicated by the adult
      attachment interview, and a lower Global Assessment of Functioning than their
      well-treated counterparts. Additionally, their prevailing moods were joyless.
      Case examples show the emergence of symptoms, personality disorders, and defenses
      over time, as well as the workings of ameliorating influences. Several of the
      maltreated children made relatively successful adaptations as adults, indicating
      children's potential for resilience. Resilience, however, may be a superficial
      concept, for, in this series of cases, seemingly adequate coping in formerly
      mistreated children always came at the price of emotional vulnerability and
      compromised potential.

PMID- 16581588
TI  - Who speaks? Who looks? Who feels? Point of view in autobiographical narratives.
AB  - In this paper, the author aims to substantiate Freud's claim that neurotic
      illness creates gaps in autobiographical narratives in terms of the narrator's
      stating and inducing perspectives. He sketches out the role of narrative
      perspective and the joint taking of a shared perspective by analyst and patient
      in psychoanalytic therapy. He introduces four ways of representing perspectives
      in narratives. Three degrees of narrative distortion are exemplified by three
      excerpts from life narratives and explored in terms of narrative perspective
      representation. The most comprehensive perspective representation is achieved in
      the first example by explicitly stating the present perspective of the narrator
      as well as the past perspective of the story's protagonist by use of mental
      verbs. In the second narrative, exclusive use of linguistic forms for inducing
      the protagonist's perspective both overwhelms the narrator and gives the listener
      an incomplete picture of what happened. Inconsistent motives, denial of
      responsibility and omission of detail render the third narrative even more
      difficult to follow. The author discusses the clinical significance of this
      exploratory analysis of perspectives in narratives in terms of claiming
      responsibility for one's past action and of level of defence mechanisms, and by
      highlighting the emotional impact on listeners, which the author suggests is the
      stronger the more perspectives are left out. He discusses analogies to
      countertransference. The analysis of narrative perspectives offers an approach
      for systematic research in psychoanalytic practice.

PMID- 16581589
TI  - Constructing the truth: from 'confusion of tongues' to 'constructions in
      analysis'.
AB  - The author hypothesizes that the papers Freud wrote in the period 1934-9
      constitute a final turning point in his work resulting from an attempt to work
      through, by means of self-analysis, early traumatic elements reactivated by the
      conditions of his life in the 1930s. The author emphasizes that the ups and downs
      of Freud's relationship with Sandor Ferenczi and the mourning which followed his
      death in 1933 played an important role in this traumatic situation. He suggests
      that through these last works, Freud pursued a posthumous dialogue with Ferenczi.
      This working through led Freud, in Moses and monotheism, to an ultimate revision
      of his theory of trauma, a revision which the author examines in full, in the
      light of the works of the Egyptologist, Jan Assmann. A new analytical paradigm
      emerges: that of constructions in analysis developed in the article of the same
      name. The activity of construction appears as an alternative to the mutual
      analysis proposed by Ferenczi and is closely bound up with the notion of
      historical truth. In psychoanalysis, it would mean constructing a historical
      truth whose anchoring in the material truth of the past is essential, though it
      should not be confused with it.

PMID- 16581590
TI  - Consultation in adolescence: hurried, terminable, interminable.
AB  - The physiological ambivalence displayed by adolescents towards dependence on
      adults is an obstacle, at least initially, to a course of psychotherapy. A
      consultation is often the only thing that can be offered to start with, and
      constitutes an essential stage even for those teenagers who go on to prove
      themselves able to benefit from therapy or analysis. The way this first meeting
      is handled is therefore crucial. The author investigates the difficulties and
      paradoxes of this consultation, the particular nature of the 'time' of the
      consultation compared to that of therapy, and the different internal attitude
      this requires of the analyst. She thus identifies two separate configurations--a
      hurried consultation and an interminable consultation--which can result when the
      consultation fails in its primary objectives. Both are connected with possible
      collusive elements in the professional linked to specific adolescent angst. The
      very detailed account of a consultation shows the 'journey' made by a 14 yearold
      starting from her urgent request to be freed from a symptom experienced as an
      incomprehensible obstacle, to her gradual development of curiosity towards
      herself and towards her own mental and emotional make-up, resulting in her
      acceptance of therapeutic treatment, which would initially have been impossible.

PMID- 16581591
TI  - Intergenerational transmission of trauma: what we have learned from our work with
      mother and infants affected by the trauma of 9/11.

PMID- 16581592
TI  - The role of consciousness in working with trauma: necessary condition or
      irrelevant distraction?

PMID- 16581593
TI  - Continuity and change in the post-Kleinian evolution in London: clinical work of
      John Steiner, Ronald Britton and Michael Feldman (1988-2004).

PMID- 16581594
TI  - Trauma, envy and revenge.

PMID- 16581595
TI  - Beyond the divan: psychoanalysis in review.

PMID- 16581596
TI  - Contemporary psychoanalysis in ethnic Chinese societies: new developments.

PMID- 16581597
TI  - On: whose Bion?

PMID- 16581599
TI  - Play Misty for me (1971): the perversion of love.

PMID- 16581601
TI  - Neonatal respiratory morbidity after elective cesarean section.
AB  - OBJECTIVE: The objective of this study was to examine the rate of respiratory
      morbidity in neonates delivered by elective cesarean delivery (ECD) at term, with
      a definite confirmation of gestational age (GA) by 1st-trimester ultrasound.
      METHODS: Consecutive women carrying a singleton pregnancy and undergoing ECD at
      term (>38 1/7 weeks), confirmed by 1st-trimester ultrasound, were included in the
      study group. Multiple gestations, cesarean section (CS) in labor, CS performed
      after rupture of membranes and induced deliveries were excluded. The control
      group included women with a singleton pregnancy at term (>38 1/7 weeks) who
      delivered spontaneously. This group of women was randomly selected during the
      study period. RESULTS: The study group included 277 women delivered by ECD. The
      control group consisted of 311 women. Five newborns in the study group and none
      in the control group were admitted to the neonatal intensive care unit (NICU) due
      to respiratory disorders (p < 0.02). Excluding diabetic women did not change the
      results. On multivariate analysis, no other factors were found to independently
      influence the risk of respiratory complications. CONCLUSION: In our study, the
      rate of respiratory morbidity was found to be significantly higher in neonates
      delivered by ECD compared to those delivered vaginally. The fact that GA was
      confirmed by 1st-trimester ultrasound makes iatrogenic prematurity an unlikely
      sole cause for this excess morbidity.

PMID- 16581602
TI  - Risk factors for preeclampsia in multiparous women: primipaternity versus the
      birth interval hypothesis.
AB  - INTRODUCTION: To determine whether the risk of preeclampsia in multiparous women
      with a previous normal pregnancy is related to changing paternity or to prolonged
      birth interval, a retrospective study was conducted at the Lyell McEwin Health
      Service (University of Adelaide). METHODS: The study included all multiparous
      women known to the hospital because of their preceding 1st delivery in the same
      hospital followed by their 2nd and/or 3rd ongoing pregnancy resulting in a
      delivery in the period 2001 - 2003. Case records were analyzed for birth
      interval, pregnancy interval, paternity and recognized risk factors such as
      booking weight and smoking. For the analysis both the International Society for
      the Study of Hypertension in Pregnancy (ISSHP) definition and the more recently
      introduced classification by the Australian Society for the Study of Hypertension
      in Pregnancy (ASSHP) were used. RESULTS: In the 656 women in this study cohort,
      148 (26.2%) women had a different partner in their 2nd and/or 3rd ongoing
      pregnancy. Using the ISSHP definition for preeclampsia, changing partners had an
      odds ratio (OR) of 1.304 (95% CI 0.43 - 3.99); using ASSHP criteria an OR of
      1.556 (95% CI 0.6506 - 3721); and looking at the combined group of pregnancy
      induced hypertensive disorders an OR of 1.99 (95% CI 1.01 - 3.89). A longer birth
      interval if anything was associated with a lower risk of preeclampsia (non
      significant), whatever definition was used. Also the inter-pregnancy interval did
      not show a consistent relation with the risk for developing a hypertensive
      complication. CONCLUSIONS: The results of this study on risk factors for
      preeclampsia in multiparous women appear to be in line with the primipaternity
      hypothesis, but are in direct contrast with the so-called birth interval
      hypothesis.

PMID- 16581603
TI  - Neighborhood deprivation and preterm birth in Plymouth, UK.
AB  - OBJECTIVE: To assess the relationship between neighborhood deprivation and the
      preterm birth rate in Plymouth, UK, using routinely collected data from a
      clinical information system. METHODS: We used a clinic-based prospective case
      register study of all births in Plymouth UK between 1 January 1996 and 31
      December 1997 combined with indices of neighborhood deprivation to assess the
      relationship between neighborhood deprivation and the preterm birth rate. Areas
      (n = 43) were classified according to the Townsend index, measuring material
      deprivation. Preterm births were compared with term births. RESULTS: The
      incidence of singleton preterm birth was 5.3% (95% confidence interval (CI) 4.6,
      6.0). The singleton preterm birth rate increased with Townsend material
      deprivation score. Crude rates increased by 31% (relative risk (RR) (95% CI) 1.31
      (0.94, 1.84), p = 0.056) among those living in the most deprived areas compared
      to those living in the least deprived areas. A stepwise binary logistic
      regression model showed an increase in the relative risk of preterm birth of 7%
      for every unit increase in the Townsend material deprivation score (RR (95% CI)
      1.07 (1.03, 1.11)). CONCLUSION: Neighborhood deprivation is related to preterm
      birth. Examining individual and neighborhood factors together may increase
      understanding of the complex causes of preterm birth.

PMID- 16581604
TI  - Is there a diurnal pattern in the clinical symptoms of HELLP syndrome?
AB  - OBJECTIVE: To determine if there is a diurnal pattern in the clinical symptoms of
      HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome. STUDY DESIGN:
      A retrospective study was performed in 134 pregnancies complicated by HELLP
      syndrome. The medical records were reviewed to describe each HELLP episode. Time
      of day was divided into three periods, day, evening, and night. The following
      parameters were categorized according to the time of day: onset of symptoms,
      consultation by the doctor, initial blood sampling, diagnosis and decrease of
      symptoms. Biochemical parameters at clinical presentation and consecutive changes
      within 24 h were recorded. RESULTS: In 65 pregnancies 77 HELLP episodes were well
      documented. Times of onset of symptoms and consultation by the doctor were
      significantly higher during the evening and night (p < 0.001), whereas times of
      diagnosis and decrease of symptoms occurred significantly more during the day (p
      < 0.001). In only 49.3% of the cases were diagnostic laboratory criteria met at
      clinical presentation. This was mainly due to platelet values in excess of 100 x
      10(9)/l. Several hours later (median 8 h, range 2-23) the decrease in platelets
      occurred. CONCLUSIONS: A diurnal pattern exists in the clinical symptoms of HELLP
      syndrome that is characterized by an exacerbation during the night and recovery
      during the day. There is a considerable delay between the onset of symptoms and
      the fulfillment of diagnostic laboratory criteria.

PMID- 16581605
TI  - Outcome of preterm and term neonates of mothers with malignant diseases diagnosed
      during pregnancy.
AB  - OBJECTIVE: To investigate the outcome of preterm and term neonates born to
      mothers with malignant diseases diagnosed during pregnancy. METHODS: A
      retrospective analysis with a matched-paired control group in a third level
      obstetric department and third level neonatal department of the University
      Hospital Frankfurt. Patients were preterm and term neonates from mothers with
      oncologic diseases diagnosed during pregnancy and matched-paired preterm and term
      neonates from healthy mothers. MEASUREMENTS AND RESULTS: Nineteen preterm and
      three term (1 x twins) neonates from 21 mothers with oncologic diseases and
      matched-paired neonates from 21 healthy mothers were included. With the exception
      of one case, pregnancy was terminated because of the necessity for maternal
      oncological treatment. Children from mothers with malignant diseases had a
      significantly lower birth weight and a tendency towards a higher incidence of
      high-grade respiratory distress syndrome. No significant differences concerning
      Apgar scores, red blood cell (RBC), white blood cell (WBC), and platelet (PLT)
      counts postpartum, and duration of hospital days between the two groups of
      neonates were observed. CONCLUSION: Direct perinatal outcome of preterm or term
      neonates from mothers with malignant diseases diagnosed during ongoing intact
      pregnancy does not differ from the outcome of a comparable group of neonates from
      healthy mothers. This might be in contrast to the long-term outcome of this
      special patient group. In our study we could find no elevated mortality in
      neonates where pregnancy was terminated because of the need for maternal
      chemotherapeutic therapy.

PMID- 16581606
TI  - Do placental sections accurately reflect umbilical cord nucleated red blood cell
      and white blood cell differential counts?
AB  - OBJECTIVE: Elevated levels of umbilical cord nucleated red blood cells (nRBCs)
      have been used to assess in utero hypoxia. Although the umbilical nRBC value has
      been the 'gold standard', umbilical blood may not be obtained at delivery. We
      determined if the levels of nRBCs and white blood cell (WBC) counts in fixed
      placental sections might serve as a proxy for cord blood values. STUDY DESIGN:
      Umbilical blood and placenta were collected from 25 deliveries at Harbor-UCLA
      Medical Center. Umbilical blood and placental sections were analyzed for nRBCs
      (per 100 WBC) and WBC differential, and compared with the t-test or the Mann
      Whitney rank sum test. RESULTS: nRBC counts were equivalent in umbilical cord and
      placental sections (5 vs. 4/100 WBC). Umbilical lymphocyte and polymorphonuclear
      leukocyte (PMN) counts were normally distributed, averaging 35 +/- 9 and 56 +/-
      2/100 WBC, respectively. Placental lymphocyte (33 +/- 2/100 WBC) and PMN (60 +/-
      2/100 WBC) counts were equivalent to cord blood values. CONCLUSION: WBC
      differentials and nRBC counts are equivalent in umbilical cord blood and
      processed placental pathology sections. For infants in whom cord blood cell
      counts are desired though umbilical cord samples are unavailable, fixed placental
      sections may serve as a proxy.

PMID- 16581607
TI  - Three-dimensional multiplanar ultrasound in a limb-body wall complex fetus:
      clinical evidence for counseling.
AB  - A rare dysmorphologic fetal anomaly at the 17th week of gestation was suspected
      during a second trimester routine scan for fetal and maternal screening data.
      First findings were significant for a severe abdominal wall defect, limb and foot
      compromised positions. Fetal biometry was appropriate in biparietal diameter and
      head circumference measurements; the long upper bones were normal both for length
      and development. The patient was referred to a prenatal unit to complete the
      sonographic diagnosis. Two- and three-dimensional sonographic investigations were
      performed and techniques were complementary for fetal maldevelopment
      specification. Limb-body wall complex with lumbosacral spine torsion and lower
      limbs with severely abnormal features were identified. With 2D color Doppler, a
      heart defect was confirmed and the umbilical cord was missing from the amniotic
      cavity. An invasive procedure by amniocentesis was made to ascertain alpha
      fetoprotein levels and fetal karyotype. Following parental counseling, pregnancy
      was terminated and feto-pathological examination confirmed the sonographic
      diagnosis. The 17-week fetus affected by limb-body wall complex is reported
      herein; 2D and 3D scans of the fetus identified organ displacement due to a
      combination of very early events.

PMID- 16581609
TI  - Ludwig's angina in pregnancy.
AB  - Ludwig's angina is an infectious process involving the submental, sublingual, and
      submandibular spaces that can rapidly progress to hemodynamic instability and
      airway loss. Treatment involves antibiotics, incision, drainage and the placement
      of extraoral drains. This is the first reported recent case of Ludwig's angina in
      a pregnant patient.

PMID- 16581608
TI  - Atrial flutter in a premature infant with a structurally normal heart.
AB  - Isolated postnatal atrial flutter (AF) with a structurally normal heart is rare
      in the neonatal period. Central lines have their inherent risks and are
      frequently used in the management of growing premature newborns. Some new
      antimicrobial agents do have pro-arrhythmic effects, proven in adults but with
      limited data available for the newborn. We present a case of atrial flutter with
      2:1 block in a 1-month-old premature baby with possible contribution from an
      intra-cardiac catheter and/or use of a broad spectrum antimicrobial.

PMID- 16581610
TI  - Neonatal myocardial infarction due to thrombotic occlusion.
AB  - Neonatal myocardial infarction is rare and its prognosis is poor. We describe the
      clinical course and autopsy findings of a newborn female with myocardial
      infarction. Her clinical course was rapidly progressive, becoming fatal before we
      could detect the cause. Autopsy demonstrated significant occlusion of the left
      coronary artery as well as evidence of new infarction, suggesting that the event
      occurred at birth. This case illustrates myocardial infarction as a possible
      cause of early neonatal death.

PMID- 16581611
TI  - A call for empirical research on best practices for economic evaluation in
      ophthalmic outcomes research.

PMID- 16581612
TI  - Uveal and conjunctival malignant melanoma in denmark 1943-97: observed and
      relative survival of patients followed through 2002.
AB  - PURPOSE: To evaluate the observed and relative survival of patients diagnosed
      with a malignant melanoma in the ocular region in Denmark during the period 1943
      97. METHODS: The study included 2,504 patients (1,292 men and 1,212 women)
      diagnosed with a melanoma in the ocular region, of which 2,434 cases could be
      topographically subclassified into 2,178 in the choroid/ciliary body, 141 in the
      iris, and 115 in the conjunctiva. The patients were followed through 2002 and the
      observed survival proportions and relative survival ratios were estimated.
      RESULTS: For the total ocular region and the choroid/ciliary body, the observed
      survival did not vary statistically significantly with the year of diagnosis. A
      statistically insignificant higher observed survival for women than men was found
      for tumors in the ocular region and the subgroups choroid/ciliary body, iris, and
      conjunctiva. During the 55-year study period, the 5- and 10-year relative
      survival remained stable for the ocular region for men at 67% and 57% and for
      women at 71% and 60%, respectively, and stable for the choroid/ciliary body for
      men at 66% and 55% and for women at 69% and 57%, respectively. The 5- and 10-year
      relative survival for the iris was for men 90% and 85% and for women 99% and
      101%, respectively, and for the conjunctiva for men 83% and 70% and for women 93%
      and 82%, respectively. CONCLUSION: The observed and relative survival of patients
      diagnosed with a melanoma in the ocular region and choroid/ciliary body in
      Denmark during the period 1943-97 and followed through 2002 has remained stable.
      The highest observed and relative survival was found for iris melanomas, the
      lowest for choroid/ciliary body melanomas, and intermediate for conjunctival
      melanomas.

PMID- 16581613
TI  - Antioxidants in prevention of cataracts in South India: methodology and baseline
      data*.
AB  - PURPOSE: To describe the methodology and baseline data for the Antioxidants in
      Prevention of Cataracts (APC) study in South India. METHODS: The APC study is a
      prospective, 5-year, randomized, triple-masked, placebo-controlled, field-based
      clinical trial to examine the effect of antioxidants (combination tablet of
      vitamins A, C, and E) on progression of cataract. The primary outcome variable is
      cataract progression (nuclear opalescence), evaluated with the slit-lamp
      biomicroscope by the Lens Opacification Classification System III method.
      Secondary outcome variables are progression in cortical and posterior subcapsular
      opacity and nuclear color, change in best corrected visual acuity, myopic shift,
      and treatment failure (progression to cataract surgery or best corrected vision
      worse than 20/400 in an eye). Inclusion criteria are age between 35 and 50 years
      and best-corrected visual acuity of 20/40 or better. Exclusion criteria are a
      diagnosis of diabetes mellitus or nonfasting blood glucose level>7.8 mmol/L,
      history or presence of various ocular conditions or treatment forms, or current
      use of vitamin supplements. Baseline ophthalmic, demographic, and potential
      cataract risk factor data (such as smoking, sunlight, or alcohol exposure) were
      compared between groups on an intent-to-treat basis. RESULTS: Of 954 people
      screened, 798 were enrolled, a sample size which exceeded the required estimate.
      More than 80% of subjects had 20/20 or better vision in at least one eye, and
      baseline prevalence of significant cataract according to the LOCS III grading
      scale was high. The two treatment groups were comparable for all baseline
      measures except alcohol intake. CONCLUSION: The sample size and group baseline
      characteristics will provide sufficient power to detect a change in cataract
      progression within 5 years.

PMID- 16581614
TI  - Decreased glucose-6-phosphate-dehydrogenase (G6PD) activity and risk of senile
      cataract in Taiwan.
AB  - G6PD deficiency may render afflicted individuals more susceptible to certain
      degenerative diseases. To clarify the relationship between G6PD deficiency and
      cataract, blood G6PD activity was determined in patients with cataract in Taiwan.
      The cases and hospital-based controls were recruited from the medical outpatient
      department and from the physical checkup department at Chang Gung Memorial
      Hospital, respectively. A questionnaire survey was used to determine associations
      between cataracts and their risk factors. G6PD activity in fresh RBC was
      quantitatively measured and genomic DNA was extracted from lymphocyte nuclei. The
      mean blood G6PD activity among cataract patients (278.1 U/10[12] RBC) was similar
      to that of normals (288.0 U/10[12] RBC). No statistically significant difference
      in the distribution of G6PD activities as grouped by an increment of 100 U/[10,
      12] RBC was observed between cataract patients and normal subjects. The
      predominant forms of G6PD gene mutation (cDNA 1376 G to T and 95 A to G) were
      both found in the patients with cataract. The adjusted odds ratio for cataract
      was 1.21 for every decrement of 100 U/10[12] RBC of G6PD activity in these
      subjects. These data indicate that G6PD activity is not a potential risk factor
      for senile cataract in Taiwan.

PMID- 16581615
TI  - Glaucoma admissions and surgery in public sector tertiary care hospitals in
      pakistan: results of a national study.
AB  - PURPOSE: To assess the annual number of glaucoma operations and admissions in the
      public sector tertiary care hospitals in Pakistan. METHODS: Eye departments in
      all 18 public tertiary care centers in the country were requested to provide data
      on the number of glaucoma operations and admissions during 1998. Of these, 13
      hospitals agreed to participate. Eye departments' log books or patients' records
      were used to collect data retrospectively on the total number of eye admissions,
      the total number of glaucoma admissions, the type of glaucoma, and the total
      number and type of glaucoma operations. RESULTS: Glaucoma accounted for 8.1%
      (1,942/23,931) of all eye admissions. Open-angle glaucoma was responsible for
      37.6% or 731 glaucoma admissions followed by secondary glaucoma (35.0%) and angle
      closure glaucoma (18.2%). During 1998, 1,407 glaucoma-related operations were
      performed in the selected hospitals. The mean (+/-SD) and the median number of
      operations performed were 108.2 (+/-59.6) and 112 (range: 17-206), respectively.
      Trabeculectomies accounted for 1,043 (74.1 %) of all procedures. Their number
      ranged from 16 to 170 (median: 84) in the selected hospitals. CONCLUSIONS: We
      believe that the annual number of glaucoma operations performed in the public
      tertiary care hospitals in Pakistan is far less than required. In-depth research
      is therefore needed to explain if this is because of gaps in service provision or
      a genuine shift to medical management of glaucoma on an outpatient basis.

PMID- 16581616
TI  - The reliability of data collection periods of personal costs associated with
      vision impairment.
AB  - PURPOSE: To determine the reliability of vision-related personal costs collected
      over 1, 3 and 6 months (extrapolated to 12 months) compared to one-year data.
      METHODS: Participants of any age, with a presenting visual acuity of < 20/40 in
      the better eye and an ability to converse in English, were recruited. Monthly
      cost diaries, in large print and electronic copies with instructions available in
      audio and Braille, were used prospectively to collect personal costs. The
      personal expenses were grouped under four categories, namely: (a) medicines,
      products and equipment, (b) health and community services, (c) informal care and
      support and (d) other expenses. Sociodemographic and clinical data were also
      collected. RESULTS: 104 participants (59 females) with a mean age of 64 years
      completed the 12-months diaries. Almost 40% of the participants had severe visual
      impairment (< 20/200) in the better eye and the most common cause of vision loss
      was AMD (n=40; 38%). The mean total personal costs collected from the 12-months
      diaries were 3,330+/-2,887 AUS dollars. There were no significant differences
      between the 12-months data and extrapolated 1, 3 and 6-months diaries (t-tests;
      p=0.17, 0.89 and 0.73, respectively). However, the 1-month variation was
      substantially larger (SD+/-5,860) compared to the 3-month and 6-month variances
      (SD+/-3,037 and 3,030, respectively) for total costs. Also, compared to the 12
      months diaries, the 1-month data consistently recorded the weakest correlation
      coefficients for all cost categories compared to the other time intervals.
      CONCLUSIONS: Given that diary completion can be particularly challenging for
      individuals with impaired vision, a minimum 3-months data collection period can
      provide reliable estimates of annual costs associated with vision impairment.

PMID- 16581617
TI  - Evaluation of an eye health program: the vision initiative.
AB  - PURPOSE: The aim of this study was to develop an innovative, rapid and economical
      assessment methodology to determine the knowledge, attitudes and behaviours
      regarding eye health and to determine the rates of the most common causes of
      visual impairment and undiagnosed eye disease. METHODS: Letters were posted to
      Seniors Card holders aged 70-79 in 18 randomly selected areas, stratified by
      socio-economic status. A questionnaire was developed to measure knowledge,
      attitudes and behaviours regarding eye health. Uncorrected refractive error was
      determined by measuring presenting and best-corrected visual acuity (VA).
      Diabetic retinopathy and age-related macular degeneration were assessed using
      digital non-mydriatic retinal photography. Glaucoma was assessed using Frequency
      Doubling Technology (FDT) and digital images of the optic nerve head. Cataract
      was determined using digital retro-illumination images of the lens taken with a
      non-mydriatic camera. The cost for recruiting, examining and grading images for
      each participant was calculated by dividing the total study cost by the number of
      participants examined. RESULTS: Of the 13,483 participants invited to participate
      in the study, appointments were made for 1860 (13.8%) people with 1,701 (91%)
      actually attending. Overall, missing data from the 1,695 questionnaires
      represented less than 1.0% and all participants attended the vision screening
      over a three-month period. Presenting and best-corrected visual acuity and FDT
      results on both eyes were obtained on 99% of the sample. The proportion of
      gradable digital images of the fundus in both eyes in the sample was 89%, while
      90% of participants with bilateral presenting VA<6/12 had assessable lens images.
      The cost for recruiting, examining and grading images for each participant was
      approximately 150 AUS dollars. CONCLUSION: The recruitment from a mailing
      obtained the required sample size for the study, allowing a large sample of
      participants to be examined efficiently over a short period of time. It is
      important that the most common causes of visual impairment and undiagnosed eye
      disease can be determined using this rapid assessment methodology.

PMID- 16581618
TI  - Validation of the Daily Living Tasks Dependent on Vision (DLTV) questionnaire in
      a U.S. population with age-related macular degeneration.
AB  - PURPOSE: The Daily Living Tasks Dependent on Vision questionnaire (DLTV) has been
      used to assess functional impairment among patients with age-related macular
      degeneration (AMD). This study evaluated the psychometric properties of the DLTV
      using patient-reported rates of use of services and devices in an outpatient
      population. METHODS: The DLTV was included in a survey mailed to members of an
      AMD advocacy organization. Included in the survey were questions about
      demographic and clinical characteristics as well as questions about use of low
      vision aids and care-giving. Respondents provided informed consent. Data were
      analyzed in SAS. RESULTS: Four respondents of 803 did not complete the DLTV;
      missing data were uncommon. Most (56%) respondents were male; the mean age was 73
      years. Internal consistency reliability of the DLTV was 0.9699. Construct
      validity was demonstrated with moderate to high correlations between the DLTV and
      use of services and devices. The DLTV demonstrated discriminant validity and
      could distinguish between respondents with different levels of impairment, i.e.,
      those who reported regular care-giving compared to those without regular care
      giving. CONCLUSIONS: In this outpatient population, the DLTV demonstrated
      reliability and validity. This analysis complements existing research and
      supports the use of the DLTV in AMD patients.

PMID- 16581619
TI  - Normal periocular anthropometric measurements in the Turkish population.
AB  - PURPOSE: To evaluate the ocular and periocular anthropometric measurements of
      Turkish subjects. METHODS: Corneal diameter, horizontal and vertical palpebral
      fissure, vertical brow-nasal distance, inter-outer canthal distance, inter-inner
      canthal distance, inter-pupillary distance, bridge height, lid crease, brow
      height, levator function, head circumference and interorbital distance were
      measured in 706 eyes of 353 subjects. RESULTS: In men, the mean corneal diameter
      was 10.5 mm, horizontal palpepral fissure was 30.0 mm, vertical palpepral fissure
      was 9.7 mm, vertical brow-nasal distance was 36.9 mm, inter-outer canthal
      distance was 91.3 mm, inter-inner canthal distance was 30.7 mm, inter-pupillary
      distance was 60.6 mm, nasal bridge height was 4.7 mm, lid crease was 6.0 mm, pre
      tarsal skin height was 2.3 mm, brow height was 9.7 mm, levator function was 14.4
      mm, interorbital distance was 99.1 mm and head circumference was 58.0 cm. In
      female subjects these measurements were 10.3 mm, 30.0 mm, 9.9 mm, 35.1 mm, 90.1
      mm, 30.2 mm, 60.1 mm, 4.3 mm, 5.9 mm, 2.1 mm, 9.9 mm, 14.6 mm, 95.8 mm and 55.9
      cm, respectively. CONCLUSION: In this study we obtained the anthropometric
      measurements of ocular and periocular structures in Turkish subjects. Knowledge
      of normal values in a population can be important in the manufacture of
      spectacles and in clinical and surgical practice.

PMID- 16581620
TI  - Attachment style, empathy, and helping following a collective loss: evidence from
      the September 11 terrorist attacks.
AB  - This study examined the relationships between avoidant and ambivalent attachment
      dimensions, empathy, and helping behavior in the context of one of the most
      tragic examples of collective loss in the USA. US college students (314 total:
      219 females, 95 males) completed questionnaires between 20 and 42 days after the
      September 11 terrorist attacks. Results from this correlational study confirm
      previous laboratory experiments finding that attachment style may be related to
      people's ability to experience empathy and engage in helping behavior. Following
      the terrorist attacks, those with lower scores on avoidant attachment (i.e., more
      secure individuals) reported greater empathy with the bereaved. No association
      was found between the anxious attachment dimension and empathy, most likely due
      to a curvilinear relationship. Empathy for the bereaved was significantly
      correlated with helping behavior. Although neither attachment dimension was
      directly associated with collective helping behavior, avoidant attachment was
      negatively and indirectly related to collective helping behavior via its
      relationship with empathy for the bereaved.

PMID- 16581621
TI  - Attachment linked predictors of women's emotional and cognitive responses to
      infant distress.
AB  - The purpose of this study was to examine associations among women's emotional and
      cognitive responses to infant fear and anger and to identify attachment linked
      predictors of these responses. Four hundred and forty Caucasian and African
      American undergraduate college women viewed video clips of two crying infants,
      one displaying anger and the other displaying fear. They identified what the
      infants were feeling, made causal attributions about the cause of crying, rated
      their own emotional reactions to the crying infants, and reported on the extent
      to which their parents met their emotional needs in childhood and their current
      adult attachment patterns. Emotional and cognitive responses to infant fear and
      anger were interrelated. Consistent with prediction, a history of parental
      emotional rejection and adult attachment anxiety and avoidance correlated
      negatively with accurate identification of emotions and positively with negative
      attributions, amusement, and neutral responses to infant distress. Adult
      attachment security moderated the effects of early parental rejection on
      emotional and cognitive responses to infant distress, and these results varied
      based on race and parent gender. Results are discussed from an attachment theory
      perspective.

PMID- 16581622
TI  - Attachment organization as a moderator of the link between friendship quality and
      adolescent delinquency.
AB  - This study examined attachment organization as a moderator of the link between
      the quality of the adolescents' current friendships and delinquent behavior. Data
      were gathered from a moderately at-risk sample of 71 ethnically and
      socioeconomically diverse adolescents. Results revealed a moderating effect of
      attachment organization (as assessed by the AAI) such that strong and supportive
      friendships were linked to lower levels of delinquency, but only when
      adolescents' attachment organization reflected an orientation toward heightened
      attention to attachment relationships (via preoccupation or via clear lack of
      dismissal of attachment). These results suggest that attachment organization
      plays an important role in delineating the conditions under which the qualities
      of social relationships are likely to be linked to important psychosocial
      outcomes.

PMID- 16581623
TI  - Effects of attachment-focused versus relationship skills-focused group
      interventions for college students with insecure attachment patterns.
AB  - This study tested the attachment issues segment of Kilmann's (1996) manualized
      attachment-focused (AF) group intervention. College students with insecure adult
      attachment patterns were randomly assigned into either a manualized attachment
      focused group or into a manualized relationship skills-focused (RS) group. A no
      intervention control condition (NC) was recruited in the same manner. Between pre
      and post-testing, AF and RS participants reported decreased agreement with
      dysfunctional relationship beliefs. AF participants also reported higher self
      esteem, decreased angry reaction, and increased control of anger. RS participants
      reported improved interpersonal styles. At the 15-18-month follow-up, AF and RS
      participants reported increased self-awareness and positive relationship
      expectations and experiences, while NC participants reported no positive changes.

PMID- 16581624
TI  - Reactive attachment disorder in maltreated twins follow-up: from 18 months to 8
      years.
AB  - The best means for the diagnosis and treatment of reactive attachment disorder of
      infancy and early childhood have not been established. Though some longitudinal
      data on institutionalized children is available, reports of maltreated young
      children who are followed over time and assessed with measures of attachment are
      lacking. This paper presents the clinical course of a set of maltreated fraternal
      twins who were assessed and treated from 19 months to 30 months of age and then
      seen in follow-up at 3 and 8 years of age. A summary of the early assessment and
      course is provided and findings from follow-up assessments of the cognitive,
      behavioral, and interpersonal functioning of each child is analysed. Follow-up
      measures, chosen to capture social-cognitive processing of these children from an
      attachment perspective, are highlighted. Finally, findings from the case are
      discussed from nosological and theoretical perspectives.

PMID- 16581625
TI  - Social communication in older age: lessons from people with aphasia.
AB  - Lessons on social communication in older age are drawn from the stories and
      qualitative case reports of three older people who have aphasia following stroke.
      Descriptive accounts of participant responses to qualitative interviews and
      stimulated recall of natural conversations, together with information from a
      social network diary, provide evidence of aspects of social communication
      relevant to the older person with aphasia. The perspectives of individuals and
      common themes relating to social communication with family and friends, the
      experience of aphasia, and living with aphasia in older age are presented. The
      prominence of conversations and the role of storytelling and of humor within the
      daily social communication of older people are illuminated.

PMID- 16581626
TI  - Perspectives of quality of life by people with aphasia and their family:
      suggestions for successful living.
AB  - Understanding the client's perspective is essential for good practitioner care in
      rehabilitation after stroke, and nothing is more relevant than enquiring directly
      about our clients' quality of life to inform our management. Relatively little is
      known about how older people with aphasia consider the quality of their current
      lives, and this article seeks to explore this issue. Four women's accounts of
      their life quality are presented, as well as their husbands' or daughter's
      accounts of their lives. Their stories share some common elements. Who you love
      or share your life with; where you live; feeling independent and/or in control;
      and engaging in satisfying activities mattered to these women's life quality. The
      impact of aphasia varies across the cases, and the need to accept change for
      successful living is illustrated in all accounts.

PMID- 16581627
TI  - Finding messages in bottles: living successfully with stroke and aphasia.
AB  - The question "What does it take to live successfully with stroke and aphasia?"
      was posed and answers were sought within already published accounts written by
      people living with aphasia. Published accounts that were identified as eligible
      and included in the study had to meet the following criteria: they had to be a
      published book or journal article that would be nationally available; they had to
      be authored or co-authored by a person with chronic aphasia due to stroke; and
      they had to be a personal narrative of some type. 28 publications meeting these
      criteria were identified through a search of bibliographic databases and
      websites, and 20 were available for analysis. 4 themes emerged. First, social
      support was identified as a critical factor in living successfully. Second,
      successful living appears to require an adaptation of one's perception of self.
      Third, most of the writers of the accounts looked to the future and set new
      goals. Finally, all of the published accounts noted the importance of taking
      charge of one's own continued communication improvement. Characteristics of the
      writers are discussed. The 4 themes are linked to the professional literature,
      and implications for future clinical work are explored. The potential bias of the
      interpreter is acknowledged.

PMID- 16581628
TI  - Success stories in aphasia.
AB  - Success in living with aphasia is discussed in the context of two couples who
      describe themselves as leading successful poststroke lives. Excerpts of
      interviews with the couples highlight some of the more salient issues and how
      each couple has come to accept and even appreciate "aphasic life."

PMID- 16581629
TI  - Living successfully with aphasia: three variations on the theme.
AB  - This article describes three individuals who live full and satisfying lives
      despite aphasia following stroke. The three were deliberately chosen to reflect
      different types and severities of aphasia and lengths of time post onset, as well
      as different prestroke lifestyles and circumstances. Commonalities as well as
      unique features of their successful adjustments are discussed. The article then
      compares them in a general way to a larger sample of individuals who live well
      with aphasia and contrasts them to another larger sample of individuals who have
      been less able to establish fulfilling lives following stroke and aphasia.
      Implications for counseling aphasic individuals and their families are discussed.

PMID- 16581631
TI  - Shedding your fears: bedside etiquette for dying patients.
AB  - Rehabilitation specialists often are uncomfortable with dying clients and
      patients. This article explores the reasons why and offers suggestions to reduce
      the discomfort, improve service, and grow as a professional and human being.

PMID- 16581630
TI  - Coping by stroke caregivers: sex similarities and differences.
AB  - Informal care provision presents many challenges. As the population ages, more
      people are forced to enter the role of informal caretaker. Despite the increase
      in the need for caregivers and the importance of providing care, there is little
      empirical research examining how men and women approach and cope with providing
      care. The current study examined stroke patients and their care providers to
      assess possible gender differences in the impact of caretaking on caretakers and
      care recipients. Results indicate no significant difference in patient well-being
      based on the gender of the caregiver. Some measures indicated that men have
      advantages as caregivers. Results are discussed with regard to the accuracy and
      utility of sex-role stereotypes about caregivers. In addition, these data provide
      potential insight about how to decrease caregiver burden, delay long-term
      hospitalization of the patient, and increase the quality of life for caretakers
      and patients.

PMID- 16581632
TI  - A preliminary investigation of barriers to achieving patient-centered
      communication with patients who have stroke-related communication disorders.
AB  - This article reports on research investigating barriers to achieving patient
      centered communication (PCC) with patients who have stroke-related communication
      disorders. A focus group, including people who had strokes and their family
      members, identified PCC issues they encounter when communicating with health care
      providers. The two key themes that emerged from this research were the desire to
      be treated with respect and the importance of allowing adequate time for a person
      with a speech disorder to communicate. Suggestions are given for improving PCC
      with people who have stroke-related communication disorders.

PMID- 16581633
TI  - The provision of health information to stroke patients within an acute hospital
      setting: what actually happens and how do patients feel about it?
AB  - This preliminary study describes how health information is provided to stroke
      patients in an acute hospital and describes their perceptions of health
      information provision. A further aim was to determine if patients with aphasia
      were disadvantaged in their receipt of information. Seven stroke patients were
      observed in hospital for an average of 102 minutes each and then interviewed
      using a semi-structured interview. When communication occurred, only 17.5% of
      communication time was spent providing information. Patients with aphasia
      received information for less time and on fewer topics. Implications regarding
      approaches to information provision for patients with and without aphasia are
      discussed.

PMID- 16581635
TI  - Control and relation: two foundational values and their consequences.
AB  - This paper explores and contrasts personal philosophies based on two different
      core values, control and relation, with respect to expectations, social
      relationships, habits of perception and interpretation, and ways of feeling
      grounded in the world. The paradigm of control is widespread in medicine and
      certain other health professions, but because it fosters unrealistic
      expectations, evokes fear and shame, and inhibits effective partnerships, it can
      actually compromise health outcomes. The paradigm of relation calls attention to
      interpersonal process and fosters receptivity and adaptability, thus enhancing
      partnership. A mature clinical approach combines these two perspectives,
      respecting both the benefits and limitations of reductionistic science and making
      room for self-organization and emergence.

PMID- 16581636
TI  - Developing common learning: the new generation project undergraduate curriculum
      model.
AB  - This paper describes the curriculum model developed for an ambitious
      interprofessional education programme for health and social care professions
      implemented in two universities in the south of England (the New Generation
      Project). An outline of how the New Generation Project has interpreted the
      meaning of interprofessional learning is presented first. This is followed by an
      outline of the structure of the programme, describing both learning in common and
      interprofessional learning components. The pedagogies underpinning this
      curriculum initiative are presented and an integrated pedagogical model,
      facilitated collaborative interprofessional learning, is proposed. The New
      Generation Project curriculum is then discussed as an extension of an established
      typology of interprofessional education.

PMID- 16581637
TI  - An exploratory analysis of an interprofessional learning environment in two
      hospital clinical teaching units.
AB  - An analysis of a teaching environment with regard to interprofessional practice
      was done using both qualitative and quantitative methods. Medical, nursing and
      other health professional staff and students from two hospital units (medical and
      surgical) completed two surveys. The students were also interviewed. Staff
      differed in survey results among disciplines, with nurses and other health
      professionals having a more positive view of interprofessional collaboration than
      physicians. Student interviews supported our hypothesis that little formal or
      informal interprofessional education occurred during clinical rotations. Students
      had little understanding of the nature of collaborative behavior, and appeared to
      learn their discipline's attitudes and practices through tacit observation of
      staff behaviors. This appears to reinforce disciplinary stereotypes, and may be a
      significant barrier to the development of collaborative practice. These results
      have implications for the design of interprofessional curriculum in clinical
      practicums.

PMID- 16581638
TI  - The Interprofessional Rural Program of British Columbia (IRPbc).
AB  - The Interprofessional Rural Program of British Columbia IRPbc was established in
      2003 as an important first step for the Province of British Columbia, Canada, in
      creating a collaborative interprofessional education initiative that engages
      numerous communities, health authorities and post-secondary institutions in
      working toward a common goal. Designed to foster interprofessional education and
      promote rural recruitment of health professionals, the program places teams of
      students from a number of health professional programs into rural and remote
      British Columbia communities. In addition to meeting their discipline specific
      learning objectives, the student teams are provided with the opportunity to
      experience the challenges of rural life and practice and advance their
      interprofessional competence. To date, 62 students have participated in the
      program from nursing, social work, medicine, physical therapy, occupational
      therapy, pharmaceutical sciences, speech language pathology, audiology,
      laboratory technology, and counseling psychology. While not without numerous
      struggles and challenges, IRPbc has been successful in meeting the program
      mandate. It has also had a number of positive outcomes not anticipated at the
      time the program was established.

PMID- 16581639
TI  - Interprofessional education in palliative care: a pilot project using popular
      literature.
AB  - A need to introduce the concepts of death and dying to the medical and health
      sciences undergraduate curriculum was identified at the University of Ottawa,
      Ontario, Canada. As care of the terminally ill is complex and requires the
      collaborative involvement of a diverse group of health care professionals, an
      interprofessional educational approach was utilized to address this need. A
      seminar course was developed using popular literature as the basis for learning,
      and offered to first and second year medical students, fourth year nursing
      students and graduate students in spiritual care. The discussion of roles and the
      provision of care within the context of works of selected literature provided a
      focus that enabled the students to transcend their disciplinary barriers, and to
      better understand the perspectives and contributions that other team members
      bring to patient care. Evaluation findings suggest that meaningful
      interprofessional education can be introduced effectively to students either
      prior to or while they are maturing in their professional roles.

PMID- 16581640
TI  - Interprofessional collaboration with service users in the development of cancer
      services: the Cancer Partnership Project.
AB  - Patient and Public Involvement (PPI) is a cornerstone of UK National Health
      Service (NHS) policy. The Cancer Partnership Project (CPP) is the leading
      national PPI initiative in cancer care. The CPP espouses a "partnership" model,
      with a "Partnership Group" - collaborative service improvement groups formed of
      NHS staff and service users - in each of 34 cancer networks in England. These
      groups aim to enable service users to influence local cancer service development
      and thereby improve the effectiveness of services. We interviewed 59 cancer
      service users and NHS staff in a reflective evaluation of CPP. Groups were active
      and visible in 30 networks, their main activities being: providing an accessible
      source of consumer opinion; prolific networking and representation; patient
      information and communication projects; and lobbying for service improvements.
      The groups exhibited some significant tensions. The motivations of professional
      staff varied markedly, and "obligatory" involvement as part of a person's job was
      counter-productive when not coupled with a "personal" belief in the value of PPI.
      Other controversial areas were the disclosure by patients' of personal health and
      treatment experiences, and emotional attachment to the group. It was concluded
      that partnership groups represent a useful PPI model, but more attention
      generally should be paid to the complexities of PPI and timescales required for
      meaningful cultural change.

PMID- 16581641
TI  - The evidence base and recommendations for interprofessional education in health
      and social care.

PMID- 16581642
TI  - The Rural Interprofessional Education Project (RIPE).

PMID- 16581648
TI  - Gene expression profiling of sarcomas.

PMID- 16581649
TI  - The role of telomeres and telomerase in the pathology of human cancer and aging.
AB  - Cellular senescence, the state of permanent growth arrest, is the inevitable fate
      of replicating normal somatic cells. Postulated to underlie this finite
      replicative span is the physiology of telomeres, which constitute the ends of
      chromosomes. The repetitive sequences of these DNA-protein complexes
      progressively shorten with each mitosis. When the critical length is bridged,
      telomeres trigger DNA repair and cell cycle checkpoint mechanisms that result in
      chromosomal fusions, cell cycle arrest, senescence and/or apoptosis. Should
      senescence be bypassed at such time, continued cell divisions in the face of
      dysfunctional telomeres and activated DNA repair machinery can result in the
      genomic instability favourable for oncogenesis. The longevity and malignant
      progression of the thus transformed cell requires coincident telomerase
      expression or other means to negate the constitutional telomeric loss.
      Practically then, telomeres and telomerase may represent plausible prognostic and
      screening cancer markers. Furthermore, if the argument is extended, with
      assumptions that telomeric attrition is indeed the basis of cellular senescence
      and that accumulation of the latter equates to aging at the organismal level,
      then telomeres may well explain the increased incidence of cancer with human
      aging.

PMID- 16581650
TI  - Gene expression in mixed type liposarcoma.
AB  - AIMS: Mixed type liposarcomas are rare. Here, we analysed the characteristics of
      an unusual case of mixed type liposarcoma, which consisted of a well
      differentiated liposarcoma (WDL) and a pleomorphic liposarcoma (PL), with a
      special emphasis on molecular alterations. METHODS: Microscopic and
      immunohistochemical approaches were used to investigate this case of mixed type
      liposarcoma, and to identify molecular alterations in this tumour, gene
      expression was examined in PL, WDL, and normal adipose tissue (NA) samples using
      a 17,000 cDNA microarray. RESULTS: The tumour mass, 9 x 5 x 5 cm, was located in
      the left upper arm of a 76-year-old man. Grossly, the proximal portion of the
      tumour was composed of a yellowish fatty lesion, whereas the distal portion of
      the tumour was whitish and necrotic in nature. Histologically, the tumour was
      composed of two distinct components. The proximal component of the tumour was a
      WDL and the distal component was a PL. Immunohistochemically, S100 protein
      immunoreactivity highlighted lipoblasts in both tumour portions. The Ki-67
      proliferation index was <1% in the WDL and 20% in the PL. MDM2 was positive in
      the WDL, but negative in the PL. p53 was negative in both areas. Numerous
      differentially expressed genes were found, which included genes coding for signal
      transduction, transcription, cell cycle, enzyme, structural protein, immune
      system and others. CONCLUSIONS: Our data demonstrate that multiple genes are
      differentially expressed in mixed type liposarcoma and suggest that these genes
      are associated with the differences in the morphological characteristics and
      pathogenesis of mixed type liposarcoma.

PMID- 16581651
TI  - Chromogenic in situ hybridisation testing for HER2 gene amplification in breast
      cancer produces highly reproducible results concordant with fluorescence in situ
      hybridisation and immunohistochemistry.
AB  - AIMS: The objective of this study was to evaluate the accuracy, ease of use and
      reproducibility of chromogenic in situ hybridisation (CISH) for HER2 testing by
      studying its inter-laboratory concordance in five Australian pathology
      laboratories. METHODS: The HER2 status of 49 breast cancers was determined by
      CISH twice in two different laboratories. Each sample had previously been tested
      by immunohistochemistry (IHC; 2+ and 3+ cases selected) and fluorescence in situ
      hybridisation (FISH). Participating laboratories were blinded to these test
      results. Oestrogen receptor (ER) status was also evaluated for each cancer.
      RESULTS: High correlation was observed between FISH and CISH results. No cases
      showing high gene amplification by FISH were scored as non-amplified by CISH
      (kappa coefficient = 1). High correlation was observed between IHC and CISH, all
      IHC 3+ samples showing amplification by CISH. Inter-laboratory CISH concordance
      was also good (kappa coefficient = 0.67). Fifty-six per cent of HER2-amplified
      samples tested ER positive, while 42% of ER-positive cases showed HER2 gene
      amplification, confirming that HER2 testing should not be confined to ER-negative
      breast cancers. CONCLUSIONS: These findings demonstrate that CISH is a robust
      test to assess HER2 status in breast cancer and therefore is an important
      addition to the HER2 testing algorithm.

PMID- 16581653
TI  - The correlation of angiogenesis with metastasis in primary cutaneous melanoma: a
      comparative analysis of microvessel density, expression of vascular endothelial
      growth factor and basic fibroblastic growth factor.
AB  - AIM: To establish whether there is a correlation between angiogenesis and
      metastasis in primary cutaneous melanoma (PCMM). METHODS: We studied the
      microvessel density and the expression of vascular endothelial growth factor
      (VEGF) and basic fibroblastic growth factor (bFGF) in 22 cases of PCMM with
      metastasis at presentation (metastatic group) and 28 cases of PCMM without
      metastasis for 24 months or more (non-metastatic group). Microvessels were
      stained with CD31/PECAM-1 antibody and counted. We assessed the proportion of
      VEGF expression in tumour cells, lymphocytes infiltrating the tumour (TIL) and
      lymphocytes at the periphery of the tumour, as well as the proportion of bFGF
      expression in tumour cell cytoplasms, nuclei and intra- and peritumoral vessels.
      RESULTS: An increased microvessel density was detected in the metastatic group
      (15-33 [24.09 +/- 5.55] versus 2-24 [12.96 +/- 6.02]). Moreover, enhanced
      expression of VEGF in tumour cells and peritumoral lymphocytes (Chi-square p =
      0.038 and p = 0.018) and bFGF in peritumoral vessels (chi(2) p = 0.013)
      correlated with the simultaneous presence of melanoma metastasis in PCMM.
      Furthermore, microvessel density was correlated with the expression of bFGF in
      peritumoral vessels (rs = 0.53, p = 0.049) and VEGF in tumour cells (rs = 0.37, p
      = 0.019). CONCLUSION: Microvessel density as well as the expression of both VEGF
      and bFGF might be informative concerning the progression of melanoma.

PMID- 16581652
TI  - Immunohistological localisation of human FAT1 (hFAT) protein in 326 breast
      cancers. Does this adhesion molecule have a role in pathogenesis?
AB  - AIMS: To examine the immunohistological expression in human breast cancers of
      human FAT1 (hFAT) protein, a recently described member of the cadherin
      superfamily, and its correlation with histological type and grade. METHODS: A
      total of 326 cases of invasive and in situ breast cancer representing a broad
      spectrum of histological subtypes were immunostained with affinity-purified
      rabbit antibodies produced to the cytoplasmic region of hFAT using a standard
      avidin-biotin system. Staining intensity was arbitrarily graded on a scale of 0
      to 3. RESULTS: All tumours showed diffuse staining for hFAT. Immunoexpression of
      the protein was generally strong in both lobular (LCIS, n = 2) and ductal in situ
      carcinoma (DCIS, n = 55). hFAT was also strongly immunoexpressed in all types of
      invasive carcinoma. Grade 3 DCIS displayed the highest hFAT intensity compared
      with lower grade tumours, with significant differences between grade 1 and 3 (p =
      0.015) and grade 2 and 3 (p = 0.047). With invasive ductal carcinomas (n = 128)
      the difference was not as clear-cut, as most tumours showed moderate (n = 63) or
      strong staining (n = 49), although grade 3 IDC revealed significantly decreased
      immunoexpression compared with grade 1 IDC (p = 0.03). CONCLUSIONS: The results
      illustrate that hFAT1 does not display the pattern of expression seen with the E
      cadherin-ss-catenin adhesion complex; however, its over-expression and diffuse
      expression in both in situ and invasive carcinoma strongly suggests a role in
      carcinogenesis. From the known functions of FAT1 it is suggested that the
      concurrent loss of classical cadherins from cell-cell junctions accompanied by
      increased FAT1 expression contributes to loss of duct formation, and increased
      cell migration and invasion.

PMID- 16581654
TI  - Histologically verified bone wax (beeswax) granuloma after median sternotomy in
      17 of 18 autopsy cases.
AB  - AIM: To evaluate the sternum from ordinary or forensic autopsy cases with a
      midline sternal cutaneous scar macro- and microscopically and using computed
      tomography (CT) to detect if the haemostatic bone sealant bone wax (beeswax) had
      been applied after median sternotomy and if the bone wax had elicited
      inflammation. METHODS: During a 3-year period, the sterna of 18 consecutive
      cadavers (15 ordinary autopsies, 3 forensic) who prior to death had undergone
      surgery with median sternotomy were examined macro- and microscopically and with
      CT. In addition, one virgin sternum was smeared with bone wax at the upper half
      after bench sternotomy, sutured and examined with CT. Unused bone wax was
      examined with CT for attenuation measurements. RESULTS: Macroscopically, bone wax
      was seen in 17 of 18 sterna. Acute inflammation was found in one, chronic
      inflammation and foreign body multinucleated giant cells were seen around the
      bone wax in 17 sterna. No inflammation was found in one. CT could only detect
      foci in the operated sterna with attenuation values from -45 to +20 Hounsfield
      units (HU) and values about -80 HU were found in the virgin sternum. Unused bone
      wax measured about -100 HU. CONCLUSIONS: Bone wax is non-resorbable and induces
      chronic inflammation in the operated sternum up to 10 years after application.
      Measurement of Hounsfield units with CT of the operated sterna could not verify
      bone wax granuloma.

PMID- 16581655
TI  - The unique expression profile of the androgen receptor gene in a rat model of
      neonatal cardiac hypertrophy.
AB  - Gender can influence many cardiovascular events, including cardiac hypertrophy.
      The presence of and dynamic changes involving androgen receptor (AR) gene
      expression are important confirmatory findings for androgen modulation in the
      pathogenesis of cardiac hypertrophy. AIMS: To determine AR expression profile
      during neonatal hypertrophy and its regression process using a rat model.
      METHODS: Relative mRNA levels of the AR gene were quantified at postnatal days 1,
      7, 14, 21 and 28 using real time PCR. RESULTS: A significant 10.6-fold decrease
      in AR transcription levels was observed at birth in neonates with cardiac
      hypertrophy (p < 0.05). Our analysis also showed a significant increase in AR
      mRNA levels at day 28, corresponding with regression of cardiac hypertrophy.
      DISCUSSION: The AR gene demonstrated a noteworthy trend in its expression
      pattern. The initial down-regulation was most likely the result of increased
      testosterone levels induced by hyperinsulinaemia and hypoglycaemia, which were
      present in neonates from diabetic mothers during pregnancy. The paradoxical
      increase in AR at day 28 suggested a potential long term-effect of the in utero
      diabetic environment.

PMID- 16581657
TI  - Evaluation of the Dako IDEIA norovirus EIA assay for detection of norovirus using
      faecal specimens from Australian gastroenteritis outbreaks.
AB  - AIMS: New techniques for detection of norovirus, a major cause of
      gastroenteritis, require ongoing evaluation. The aim of this study was to use
      material from gastroenteritis outbreaks in Victoria, Australia, to evaluate the
      sensitivity and specificity of the Dako IDEIA norovirus EIA assay, using both
      photometric and visual analysis. METHODS: A total of 130 faecal specimens from 41
      gastroenteritis outbreaks were tested for norovirus by electron microscopy (EM),
      a two-round multiplex reverse transcription-polymerase chain reaction (RT-PCR)
      method and the IDEIA norovirus assay. All specimens with sufficient amplified
      product were sequenced to determine their norovirus genotype. In addition, six
      well-established RT-PCR protocols were used to test four EIA-positive, multiplex
      RT-PCR/EM-negative specimens. Also, a range of RT-PCR protocols was used to test
      a specimen positive for GII only by the multiplex RT-PCR but positive for GI and
      GII by the EIA. The effect of multiple freezing-thawing cycles on EIA positivity
      was tested on seven additional specimens. A further seven specimens, known to
      contain the gastroenteritis viruses sapovirus, adenovirus, astrovirus and
      rotavirus were also tested by the IDEIA norovirus assay. RESULTS: The IDEIA
      norovirus assay gave a single-specimen sensitivity and specificity of 66% and
      85%, respectively (visual analysis compared with the multiplex RT-PCR), 63% and
      88% (photometric analysis compared with the multiplex RT-PCR), 65% and 87%
      (visual analysis compared with the multiplex RT-PCR and/or EM) and 62% and 90%
      (photometric analysis compared with the multiplex RT-PCR and/or EM). None of the
      four EIA-positive specimens negative by the multiplex RT-PCR and/or EM was
      positive by any of the six alternative RT-PCR protocols. The specimen positive
      for GI and GII by EIA but for GII only by the multiplex RT-PCR was not positive
      for GI by any of the alternative RT-PCR protocols. A minimum of three specimens
      per outbreak had to be tested by the EIA to ensure that norovirus-positive
      outbreaks (multiplex RT-PCR and/or EM) were classified as positive for norovirus
      by the IDEIA norovirus assay (visual or photometric analysis). However, one
      specimen from a norovirus-negative outbreak (multiplex RT-PCR and/or EM) for
      which four specimens were provided was positive for norovirus by the IDEIA
      norovirus assay. Seven norovirus genotypes were identified by open reading frame
      1 sequencing analysis and specimens from all seven norovirus genotypes (as well
      as an EM-positive/multiplex RT-PCR-negative specimen) were detected by the IDEIA
      norovirus assay by both visual and photometric analysis. Repeated freezing
      thawing cycles (up to six) for faecal specimens did not reduce the sensitivity of
      the EIA assay but could render an EIA-negative specimen EIA-positive. The
      specimens positive for sapovirus, adenovirus, astrovirus and rotavirus were EIA
      negative. CONCLUSIONS: The IDEIA norovirus assay lacks the sensitivity and
      specificity to ascribe a particular result to a particular specimen, but could be
      useful for detecting norovirus in a gastroenteritis outbreak where specimens are
      plentiful, although it is difficult to avoid a risk of false positives. Since
      visual analysis can be used for result assessment almost as reliably as
      photometric analysis, the test kit would be useful for laboratories lacking
      specialist equipment such as a photometric microplate reader.

PMID- 16581656
TI  - Anti-streptococcal antibodies in the diagnosis of acute and post-streptococcal
      disease: streptokinase versus streptolysin O and deoxyribonuclease B.
AB  - AIMS: To establish population normal values and compare the diagnostic value of
      antibodies against streptokinase (ASK), streptolysin O (ASO) and
      deoxyribonuclease B (ADNaseB) singularly and in combinations in acute and post
      streptococcal disease. METHODS: A retrospective analysis of serological results
      was performed to define population norms. Subjects with acute culture-confirmed
      infection and post-streptococcal disease were assessed using population norms, as
      were matched controls. The sensitivity and specificity of each antibody assay and
      of combinations of the different assays were calculated. RESULTS: Age specific
      population normal values were derived from 2,321 specimens. None of the three
      antibodies alone or in combination was a reliable marker of acute streptococcal
      infection. The sensitivity and specificity of a single antibody titre in post
      streptococcal disease ranged from 70.5 to 72.7% and 86.4 to 93.2%, respectively.
      The combination of ASO and ADNaseB was the most sensitive and specific
      combination for identifying post-streptococcal disease (sensitivity 95.5%,
      specificity 88.6%). CONCLUSIONS: In the diagnosis of acute and post-streptococcal
      disease, the addition of ASK does not increase the sensitivity or specificity of
      serological testing. A combination of ASO and ADNaseB is required in post
      streptococcal disease to achieve maximum sensitivity and specificity.

PMID- 16581660
TI  - Neuromuscular and vascular hamartoma arising in a Meckel's diverticulum.

PMID- 16581659
TI  - Postmortem findings at 36 weeks gestation in trichorhinophalangeal syndrome: a
      case report.

PMID- 16581658
TI  - Test and teach. Number fifty-three. A rare cause of Cushing's syndrome.

PMID- 16581662
TI  - Reactive plasmacytic infiltration with numerous Russell bodies involving the
      uterine cervix: 'Russell body cervicitis'.

PMID- 16581661
TI  - A papillary fibroelastoma on a papillary muscle of the left ventricle.

PMID- 16581663
TI  - Uterine plexiform leiomyomatosis with an intrinsic granulomatous response.

PMID- 16581664
TI  - Sinonasal neuroendocrine carcinoma: case report with FNA findings.

PMID- 16581665
TI  - Mucinous variant of follicular carcinoma of the thyroid gland.

PMID- 16581666
TI  - Intracortical chondroma in a 7-year-old boy and literature review.

PMID- 16581667
TI  - Primary localised nodular amyloidosis of the eyelid and conjunctiva: a case
      report.

PMID- 16581668
TI  - The use of p16INK4a as an adjunct to the interpretation of cervical biopsies.

PMID- 16581671
TI  - Factors involved in the colonisation of building facades by algae and
      cyanobacteria in France.
AB  - Algae and cyanobacteria are colonisers of building facades. A multivariate
      analysis of data gathered during a sampling campaign around France proved that
      precipitation, hygrometry, thermal amplitude, distance from the sea and proximity
      to vegetation were environmental parameters influencing this colonisation. Other
      influencing factors could be attributed to the nature of the facade coating,
      mineral substrata being more frequently colonised, and to the architecture,
      favouring in some cases the formation of damp conditions and thus the
      colonisation of the building envelope.

PMID- 16581672
TI  - Quantification of algal biofilms colonising building materials: chlorophyll a
      measured by PAM-fluorometry as a biomass parameter.
AB  - The aim of this study was to quantify algal colonisation on anthropogenic
      surfaces (viz. building facades and roof tiles) using chlorophyll a (chl a) as a
      specific biomarker. Chl a was estimated as the initial fluorescence F0 of 'dark
      adapted' algae using a pulse-modulated fluorometer (PAM-2000). Four isolates of
      aeroterrestrial green algae and one aquatic isolate were included in this study.
      The chl a concentration and F0 showed an exponential relationship in the tested
      range between 0 and 400 mg chl a m(-2). The relationship was linear at chl a
      concentrations <20 mg m(-2). Exponential and linear models are presented for the
      single isolates with large coefficients of determination (exponential: r2 > 0.94,
      linear: r2 > 0.92). The specific power of this fluorometric method is the
      detection of initial algal colonisation on surfaces in thin or young biofilms
      down to 3.5 mg chl a m(-2), which corresponds to an abundances of the
      investigated isolates between 0.2 and 1.5 million cells cm(-2).

PMID- 16581673
TI  - Drinking water biofilm assessment of total and culturable bacteria under
      different operating conditions.
AB  - Monitoring of biofilms subjected to different operating conditions was performed
      using a flow cell system. The system was fed by chlorine-free tap water, with and
      without added nutrients (0.5 mg l(-1) carbon, 0.1 mg l(-1) nitrogen and 0.01 mg
      l(-1) phosphorus), and biofilms were grown on polyvinyl chloride (PVC) and
      stainless steel (SS) coupons, both in laminar and turbulent flow. The parameters
      analysed were culturable cells, using R2A, and total bacteria, which was assessed
      using the 4,6-diamino-2-phenylindole (DAPI) staining method. The impact of the
      different operating conditions in the studied parameters was established using
      Multivariate Analysis of Variance (MANOVA). From the most relevant to the least
      relevant factor, the total and culturable bacteria in biofilms increased due to
      the addition of nutrients to water (F = 20.005; p < 0.001); the use of turbulent
      (Re = 11000) instead of laminar (Re = 2000) hydrodynamic flows (F = 9.173; p <
      0.001); and the use of PVC instead of SS as the support material (F = 2.848; p =
      0.060). Interactions between these conditions, namely between surface and flow (F
      = 8.235; p < 0.001) and also flow and nutrients (F = 5.498; p < 0.05) have also
      proved to significantly influence biofilm formation. This work highlights the
      need for a deeper understanding of how the large spectrum of conditions interact
      and affect biofilm formation potential and accumulation with the final purpose of
      predicting the total and culturable bacteria attached to real drinking water
      distribution pipes based on the system characteristics.

PMID- 16581674
TI  - Less inhibited with age? Larval age modifies responses to natural settlement
      inhibitors.
AB  - As larvae of marine invertebrates age, their response to settlement cues can
      change. This change can have significant consequences to both the ecology of
      these organisms, and to their response to antifouling coatings. This study
      examines how larval age affects the settlement response of larvae to two
      naturally derived settlement inhibitors, non-polar extracts from the algae
      Delisea pulchra and Dilophus marginatus, the former of which contains compounds
      that are in commercial development as antifoulants. Two species of marine
      invertebrates with non-feeding larvae were investigated: the bryozoans
      Watersipora subtorquata and Bugula neritina. Larval age strongly affected larval
      settlement, with older larvae settling at much higher rates than younger larvae.
      Despite having strong, inhibitory effects on young larvae, the non-polar extracts
      did not inhibit the settlement of older larvae to the same degree for both
      species studied. The results show that the effects of ecologically realistic
      settlement inhibitors are highly dependent on larval age. Given that the age of
      settling larvae is likely to be variable in the field, such age specific
      variation in settlement response of larvae may have important consequences for
      host-epibiont interactions in natural communities.

PMID- 16581675
TI  - Super-hydrophobicity fundamentals: implications to biofouling prevention.
AB  - The theory of wetting on super-hydrophobic surfaces is presented and discussed,
      within the general framework of equilibrium wetting and contact angles. Emphasis
      is put on the implications of super-hydrophobicity to the prevention of
      biofouling. Two main lines of thought are discussed, viz. i) "mirror imaging" of
      the Lotus effect, namely designing a surface that repels biological entities by
      being super-hydrophilic, and ii) designing a surface that minimises the water
      wetted area when submerged in water (by keeping an air film between the water and
      the surface), so that the suspended biological entities have a low probability of
      encountering the solid surface.

PMID- 16581676
TI  - Quantification of the effect of flowrate on the rates of arrival and attachment
      to glass of Pseudomonas aeruginosa.
AB  - Sets of time lapse sequences (movies) of pseudomonad cells attaching in each of
      six flowcells operated at Reynolds numbers from 96-2220 were obtained over a 3-d
      period. The interval between images varied between 1 s and 24 min, which allowed
      a range of different cell behaviours to be observed. The rate of accumulation of
      the cells on the surface was determined for each flowrate. Analysis of the images
      showed that the residence time distributions of the attaching cells were of the
      same form as those recorded previously in the literature. This showed that up to
      50% of the cells that arrived sufficiently close to the surface to be considered
      temporarily attached, left the surface within 1 s of arrival. Use of an
      analytically derived algorithm allowed the rate of arrival of the cells to be
      estimated. Data showed that for every cell attaching on a relatively permanent
      basis, between 20 and 35 cells arrived at the surface.

PMID- 16581677
TI  - Bioassay-guided fractionation of antifouling compounds using computer-assisted
      motion analysis of brown algal spore swimming.
AB  - Antifouling extracts from the sea stars Astropecten articulatus and Luidia
      clathrata and from the brittle star Astrocyclus caecilia were fractionated by
      solid phase extraction and high performance liquid chromatography. Bioactive
      fractions were identified with the use of computer-assisted motion analysis-based
      bioassays utilising previously described Hincksia irregularis spore swimming
      behaviour parameters. Quantified parameters of spore movement were rate of change
      of direction (RCD) and speed (SPEE). The methods used initially required only 10
      microg equivalent amounts of total crude extract and each resultant resolving
      step (normalised to 1 mg ml(-1) of crude, unfractionated extract) required far
      less material. Statistical analyses of RCD and ratios of RCD:SPEE values in
      experiments comparing swimming in the presence of extract fractions to controls
      revealed that both parameters were useful individually and in combination for
      efficiently following compound bioactivity throughout the fractionation
      procedure. This technique was also able to detect synergistic or additive
      interactions between compounds.

PMID- 16581679
TI  - Optimal treatments for hyperpigmentation.
AB  - The current treatment of hyperpigmentation relies on multiple modalities to
      achieve satisfactory cosmetic results. Patients are savvy consumers who often
      present to physicians asking about the latest treatments and breakthroughs. By
      combining topical bleaching agents, chemical peels, laser therapy, and adequate
      photo-protection, many pigmentary disorders can be successfully treated. A review
      of recent trials and new technologies will be discussed.

PMID- 16581680
TI  - Split-face comparison of radiofrequency versus long-pulse Nd-YAG treatment of
      facial laxity.
AB  - BACKGROUND AND OBJECTIVE: To improve photoaging skin with laser treatment,
      multiple sessions have been considered necessary to achieve results comparable
      with one radiofrequency (RF) treatment. We compared single-treatment improvements
      obtained by the long-pulse 1064 nm Nd:YAG laser and RF device. STUDY
      DESIGN/MATERIALS AND METHODS: In a split-face study, patients with sagging skin
      were treated once with laser (left side) and once with RF (right side) energy.
      RESULTS: Improvement judged by six blinded observers was greater for wrinkles and
      laxity (30% median) on the laser-treated side and essentially the same with both
      modalities (15% median) for texture, pores, and pigmentation. Improvement was
      maintained for at least 2-6 months on both facial sides without adverse effects.
      CONCLUSION: With a single treatment, both the long-pulse 1064 nm Nd:YAG laser and
      ThermaCool RF device provide a modest degree of improvement in both wrinkles and
      laxity of facial skin and similar improvement in texture, pores, and
      pigmentation.

PMID- 16581681
TI  - Laser skin resurfacing with a novel portable erbium:YAG laser.
AB  - BACKGROUND AND OBJECTIVE: The erbium:YAG laser is a popular modality for laser
      skin resurfacing (LSR). This study was performed to evaluate the safety and
      efficacy of a new portable Er:YAG laser in the treatment of photo-damaged skin.
      METHODS: Nine patients with skin types I-III were treated for rhytides, large
      pores, pigmented lesions, lentigines and photo-damage. Small facial areas such as
      the periorbital area, nose, cheeks, and upper lip were treated with one to six
      passes at 5-6 J/cm2 with a new portable Er:YAG laser. Topical and local
      anesthesia was used. RESULTS: All treated areas showed improvement and, depending
      upon the number of passes, re-epithelialization was complete within 2-7 days. The
      intense erythema resolved within 7 days and there was blending of treated and
      untreated areas within 2 weeks. CONCLUSION: The technique of applying a tailored
      number of 5-6 J/cm2, 300 micros pulses of a new portable Er:YAG laser to small
      areas appears to be safe and effective. There was minimal discomfort and a high
      level of patient satisfaction after a relatively short recovery time.

PMID- 16581682
TI  - Use of the pulsed infrared diode laser (904 nm) in the treatment of alopecia
      areata.
AB  - BACKGROUND: Alopecia areata is a rapid and complete loss of hair in one or
      several patches, usually on the scalp, affecting both males and females equally.
      It is thought to be an autoimmune disease which is treated with different
      modalities with variable success. Laser treatment of different wavelengths has
      been used in the management of this problem. OBJECTIVE: To study the effect of
      the pulsed infrared diode laser (904 nm) in the treatment of alopecia
      areata.Methods. Sixteen patients with 34 resistant patches that had not responded
      to different treatment modalities for alopecia areata were enrolled in this
      study. In patients with multiple patches, one patch was left as a control for
      comparison. Patients were treated on a four-session basis, once a week, with a
      pulsed diode laser (904 nm) at a pulse rate of 40/s. A photograph was taken of
      each patient before and after treatment. RESULTS: The treated patients were 11
      males (68.75%) and five females (31.25%). Their ages ranged between 4 and 50
      years with a mean of 26.6+/-SD of +/-13.8, and the durations of their disease
      were between 12 months and 6 years with a mean of 13.43+/-SD of +/-18.34.
      Regrowth of hair was observed in 32 patches (94%), while only two patches (6%)
      failed to show any response. No regrowth of hair was observed in the control
      patches. The regrowth of hair appeared as terminal hair with its original color
      in 29 patches (90.6%), while three patches (9.4%) appeared as a white villous
      hair. In patients who showed response, the response was detected as early as 1
      week after the first session in 24 patches (75%), while eight patients (25%)
      started to show response from the second session. CONCLUSION: The pulsed infrared
      diode laser is an effective mode of therapy with a high success rate for
      resistant patches of alopecia areata.

PMID- 16581683
TI  - Light-emitting diode 415 nm in the treatment of inflammatory acne: an open-label,
      multicentric, pilot investigation.
AB  - BACKGROUND: The management of acne remains a challenge, with current therapies
      linked to significant side effects and patient non-compliance. Phototherapy using
      blue light has been proven in the treatment of acne vulgaris and offers the
      clinician an effective alternative. OBJECTIVE: To determine the effect of
      narrowband light-emitting diode (LED) blue light in the reduction of inflammatory
      and non-inflammatory lesions in patients with mild to moderate acne and to
      evaluate patient tolerance of the therapy. METHODS: Forty-five patients were
      treated with high-intensity pure blue light, 415 nm and 48 J/cm2, receiving two
      treatments of 20 minutes per week for a period of 4-8 weeks. Clinical assessment
      was performed at baseline, and 2, 4 and 8 weeks after treatment. A patient's
      therapeutic response was measured using a global improvement scoring system.
      RESULTS: The mean improvement score was 3.14 at 4 weeks and 2.90 at 8 weeks. Nine
      patients experienced complete clearing at 8 weeks. The treatment was well
      tolerated, with 50% of patients highly satisfied with the treatment. CONCLUSION:
      This open-label study suggests the therapeutic efficacy of high-intensity LED
      pure blue light in the treatment of acne vulgaris with no reported side effects.

PMID- 16581684
TI  - Fractional photothermolysis for the treatment of surgical scars: a case report.
AB  - BACKGROUND: Surgical scars are a challenging condition to treat. Fractional
      photothermolysis provides a promising new modality for treatment. CASE REPORT: A
      55-year-old white female patient with a surgical scar on the chin was treated
      with fractional photothermolysis (1550 nm Fraxel SR laser). A single treatment
      session was performed at pulse energy of 8 mJ (MTZ) and a final density of 2000
      MTZ/cm2. The treatment response was assessed by comparing pre- and 2-week post
      treatment clinical photography. RESULTS: A greater than 75% clinical improvement
      of scarring was achieved at 2 weeks after a single treatment based on independent
      physician assessment. No significant adverse effects were noted. The improvement
      was persistent at 1-month follow-up. CONCLUSION: Fractional photothermolysis
      offers a new, effective, and safe modality for the treatment of surgical scars.

PMID- 16581685
TI  - Red light-emitting diode (LED) therapy accelerates wound healing post
      blepharoplasty and periocular laser ablative resurfacing.
AB  - BACKGROUND AND AIMS: Blepharoplasties can be associated with sequelae-related
      patient downtime, often extended or reinforced by periocular laser ablative
      resurfacing. The present controlled study examined the effects of a new
      generation LED phototherapy system on enhancing wound healing following such
      combination surgery. METHODS: Two males and eight females participated in the
      trial, with ages ranging from 44 to 59 years (average 52.3 years). Following
      blepharoplasty and Er:YAG/CO2 laser ablative resurfacing, one-half of each
      subject's face was treated with the red LED therapy (20 min, 96 J/cm2, 633 nm),
      the contralateral half being the unirradiated control. Patients reported
      subjectively on pain levels and resolution. Resolution of erythema, edema,
      bruising and days to healing were independently evaluated from the clinical
      photography. All findings were compared between the treated and untreated sides.
      RESULTS: In all instances, the LED therapy-treated side was statistically
      significantly superior to the unirradiated control by a factor of two to three.
      CONCLUSIONS: In this small series of 10 patients, red LED phototherapy after
      blepharoplasty and laser ablative resurfacing cut the time to resolution of side
      effects and the healing time by one-half to one-third compared with contralateral
      unirradiated controls. Further studies are warranted with larger populations to
      confirm these findings.

PMID- 16581686
TI  - Six players on the inner stage: Using ego state therapy with the medically ill.
AB  - The symptoms of medical illness often speak through eloquent, embedded metaphors
      that express deeper unconscious conflicts and meanings. Therapeutic attunement to
      the multilayered issues associated with a patient's illness can be instrumental
      in the uncovering and working through conflicts that may impede both physical and
      emotional healing. Among hypnotically facilitated psychotherapeutic approaches
      that can be helpful, ego state techniques offer rapid access to these illness
      associated issues. This article discusses six different ego states that are key
      players in the illness drama for many patients. Five of these are indwelling
      components of the patient's psyche, whereas the sixth player belongs to the
      therapist's resonant self. All of them are relevant when the practitioner seeks
      to facilitate deeper healing in patients with mind/body conditions.

PMID- 16581687
TI  - Hypnosis delivered through immersive virtual reality for burn pain: A clinical
      case series.
AB  - This study is the first to use virtual-reality technology on a series of clinical
      patients to make hypnotic analgesia less effortful for patients and to increase
      the efficiency of hypnosis by eliminating the need for the presence of a trained
      clinician. This technologically based hypnotic induction was used to deliver
      hypnotic analgesia to burn-injury patients undergoing painful wound-care
      procedures. Pre- and postprocedure measures were collected on 13 patients with
      burn injuries across 3 days. In an uncontrolled series of cases, there was a
      decrease in reported pain and anxiety, and the need for opioid medication was cut
      in half. The results support additional research on the utility and efficacy of
      hypnotic analgesia provided by virtual reality hypnosis.

PMID- 16581688
TI  - Mindfulness, acceptance, and hypnosis: Cognitive and clinical perspectives.
AB  - The authors propose that hypnosis and mindfulness-based approaches can be used in
      tandem to create adaptive response sets and to deautomatize maladaptive response
      sets. They summarize recent research on the effectiveness of mindfulness-based
      approaches in clinical and nonclinical contexts and propose that the cognitive
      underpinnings of mindfulness approaches can be conceptualized in terms of the
      metacognitive basis of mindful attention, Toneatto's elucidation of the Buddhist
      perspective on cognition, and Kirsch and Lynn's response-set theory. They also
      suggest that mindfulness can serve as a template for generating an array of
      suggestions that provides cognitive strategies to contend with problems in living
      and to ameliorate stress and negative affect more generally. Many of the ideas
      the authors advance are speculative and are intended to spur additional research
      and clinical work.

PMID- 16581689
TI  - The special effects of hypnosis and hypnotherapy: A contribution to an ecological
      model of therapeutic change.
AB  - There is ample evidence that hypnosis enhances the effectiveness of psychotherapy
      and produces some astounding effects of its own. In this paper, the effective
      components and principles of hypnosis and hypnotherapy are analyzed. The
      "special" hypnotic and hypnotherapeutic effects are linked to the fact that the
      ecological requirements of therapeutic change are taken into account implicitly
      and/or explicitly when working with hypnotic trances in a therapeutic setting.
      The hypnotic situation is described--theoretically and in case examples--as a
      therapeutic modality that gratifies and aligns the basic emotional needs to feel
      autonomous, related, competent, and oriented. It is shown how the hypnotic
      relationship can help promote a sound ecological balance between these needs--a
      balance that is deemed to be a necessary prerequisite for salutogenesis.
      Practical implications for planning hypnotherapeutic interventions are discussed.

PMID- 16581690
TI  - Anatomy of a hypnotic response: Self-report estimates, actual behavior, and
      physiological response to the hypnotic suggestion for arm rigidity.
AB  - The present study closely examines subject response to the arm-rigidity item of
      the HGSHS:A. Subject behavior, subject self-report, and surface EMG of the biceps
      and triceps muscles were monitored. Two distinct ways of passing the item were
      observed and verified by EMG recordings: some subjects (tremblers) exerted
      muscular effort to bend the arm and kept it rigidly straight. Others
      (nontremblers) passively kept the arm straight without exerting muscular effort
      to bend, even though they reported exerting effort to bend their arm. These two
      behaviorally and physiologically different methods of passing the item support
      the idea of individual differences in hypnotic responding and suggest that
      subjects may be using different mental processes to pass the item.

PMID- 16581691
TI  - Suggestions of altered balance: Possible equivalence of imagery and perception.
AB  - Hypnotic suggestions describing an altered perception induce congruent changes in
      the subject's experience and behavior. However, it is not known whether an
      implicit suggestion, only indirectly referring to an altered perception, induces
      a behavioral response corresponding to that of the real situation. In this study,
      an implicit suggestion of backward falling (IMP) was given to high hypnotizable
      participants not exposed (W-Highs) and exposed (H-Highs) to a hypnotic induction
      and a group of low hypnotizable individuals (W-Lows). Their posture was evaluated
      through an elite system. The results after the IMP were compared with those after
      an explicit suggestion of backward falling (EXP). In both W-Highs and H-Highs,
      the IMP elicited the backward body sway expected in the corresponding real
      situation, whereas no response was found in W-Lows. The results are discussed in
      terms of a possible equivalence of imagery and perception or of a lack of the
      motor inhibition normally associated with motor imagery.

PMID- 16581692
TI  - A meta-analysis of gender, smoking cessation, and hypnosis:a brief communication.
AB  - Results of a meta-analysis showed that males were more likely to report smoking
      abstinence than female participants following hypnosis-based treatments for
      smoking. Across 12 studies that used hypnosis in the treatment of smoking and
      reported outcome statistics by gender, the authors found that the odds of
      achieving smoking abstinence were 1.37 times greater for male than female
      participants. The results are consistent with the nonhypnosis literature
      suggesting that females have a more difficult time achieving smoking abstinence
      compared to males.

PMID- 16581693
TI  - Motor and sensory dissociative phenomena associated with induced catalepsy: A
      brief communication.
AB  - The purpose of this study was to investigate dissociative symptoms that may occur
      as an epiphenomenon of tactile-induced catalepsy. In 15 participants, catalepsy
      was induced in the right arm, and dissociative symptoms were evaluated using a
      self-report questionnaire. In comparison with the left, noncataleptic arm, the
      right cataleptic arm was perceived differently. In addition to increased
      rigidity, the cataleptic arm was characterized by the presence of paresthesias, a
      decreased perception of sense and a decreased awareness of the arm. Moreover, the
      self-reported changes in perception were significantly correlated to the
      hypnotically induced arm-immobilization part of the Stanford Hypnotic
      Susceptibility Scale. In conclusion, catalepsy induction elicits a variety of
      dissociative symptoms and provides a useful research paradigm for the study of
      motor-perceptual dissociative phenomena.

PMID- 16581695
TI  - Pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension is a disease of the small pulmonary arteries
      characterized by vascular narrowing and increased pulmonary vascular resistance,
      which eventually leads to right ventricular failure. Vasoconstriction, vascular
      proliferation, remodeling of the pulmonary vessels, and thrombosis are all
      contributing factors to the increased vascular resistance seen in this disease.
      Pulmonary arterial hypertension develops as a sporadic disease (idiopathic), as
      an inherited disorder (familial), or in association with certain conditions
      (collagen vascular diseases, portal hypertension, human immunodeficiency virus
      infection, congenital systemic-to-pulmonary shunts, ingestion of drugs or dietary
      products, or persistent fetal circulation). The pathogenesis of pulmonary
      arterial hypertension is a complicated, multifactorial process. It seems doubtful
      that any one factor alone is sufficient to activate the necessary pathways
      leading to the development of this disease. Rather, clinically apparent pulmonary
      arterial hypertension most likely develops after a second insult occurs in an
      individual who is already susceptible owing to genetic factors, environmental
      exposures, or acquired disorders. Currently, there is no cure for pulmonary
      arterial hypertension but several novel therapeutic options are now available
      that can improve symptoms and increase survival.

PMID- 16581694
TI  - Pharmacogenomics and antidepressant drugs.
AB  - While antidepressant pharmacotherapy is an effective treatment of depression, it
      still is hampered by a delayed time of onset of clinical improvement and a series
      of side effects. Moreover, a substantial group of patients has only limited
      response or fails to respond at all. One source accounting for these variations
      are genetic differences as currently analysed by single nucleotide polymorphisms
      (SNP) mapping. In recent years a number of pharmacogenetic studies on
      antidepressant drugs have been published. So far they mostly focused on
      metabolizing enzymes of the cytochrome P450 (CYP) families and genes within the
      monoaminergic system with compelling evidence for an effect of CYP2D6
      polymorphisms on antidepressant drug plasma levels and of a serotonin transporter
      promoter polymorphism on clinical response to a specific class of
      antidepressants, the selective serotonin reuptake inhibitors. It is clear,
      however, that other candidate systems have to be considered in the
      pharmacogenetics of antidepressant drugs, such as neuropeptidergic systems, the
      hypothalamus-pituitary adrenal (HPA) axis and neurotrophic systems. There is
      recent evidence that polymorphisms in genes regulating the HPA axis have an
      important impact on response to antidepressants. These studies mark the beginning
      of an emerging standard SNP profiling system that ultimately allows identifying
      the right drug for the right patient at the right time.

PMID- 16581696
TI  - Treatment of multiple myeloma: an emphasis on new developments.
AB  - Not all patients who fulfill the minimal criteria for diagnosis of multiple
      myeloma should be treated. If doubt exists about beginning therapy, one should
      wait and re-evaluate the patient in 2 or 3 months. There is no evidence that
      early treatment of multiple myeloma is advantageous. All patients should be
      considered possible candidates for an autologous stem cell transplantation. If
      they are deemed to be eligible, they should be treated for 3 to 4 months with
      therapy that does not damage the hematopoietic stem cells. Currently, most
      physicians use thalidomide plus dexamethasone or dexamethasone alone for
      induction. Vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) have
      been used in the past. Autologous stem cell transplantation prolongs disease-free
      survival and overall survival. The treatment-related mortality rate is 1% to 2%.
      Melphalan, 200 mg/m2, is the most widely used preparative regimen. Although
      allogeneic transplantation is attractive, the mortality rate (about 20%) is too
      high to recommend conventional allogeneic transplantation. Non-myeloablative
      transplantation is currently under investigation. If the patient is not a
      candidate for autologous stem cell transplantation, therapy with melphalan and
      prednisone is a good choice. Patients with relapsed or refractory disease may be
      treated with dexamethasone, thalidomide and dexamethasone, bortezomib (Velcade,
      PS-341), or lenalidomide (Revlimid, not yet approved by the Food and Drug
      Administration).

PMID- 16581698
TI  - Asymmetric dimethylarginine (ADMA): a novel risk marker in cardiovascular
      medicine and beyond.
AB  - There is abundant evidence that the endothelium plays a crucial role in the
      maintenance of vascular tone and structure. One of the major endothelium-derived
      vasoactive mediators is nitric oxide (NO), an endogenous messenger molecule
      formed in healthy vascular endothelium from the amino acid precursor L-arginine.
      Endothelial dysfunction is caused by various cardiovascular risk factors,
      metabolic diseases, and systemic or local inflammation. One mechanism that
      explains the occurrence of endothelial dysfunction is the presence of elevated
      blood levels of asymmetric dimethylarginine (ADMA)--an L-arginine analogue that
      inhibits NO formation and thereby can impair vascular function. Supplementation
      with L-arginine has been shown to restore vascular function and to improve the
      clinical symptoms of various diseases associated with vascular dysfunction.

PMID- 16581697
TI  - Treatment of airway mucus hypersecretion.
AB  - Airway mucus hypersecretion is now recognized as a key pathophysiological feature
      in many patients with asthma, chronic obstructive pulmonary disease (COPD) and
      cystic fibrosis. Consequently, it is important to develop drugs that inhibit
      mucus hypersecretion in these susceptible patients. Conventional therapies,
      including anticholinergics, ss2-adrenoceptor agonists, corticosteroids,
      mucolytics and macrolide antibiotics, have variable efficacy in inhibiting airway
      mucus hypersecretion, and are less effective in COPD than in asthma. Novel
      pharmacotherapeutic targets are being investigated, including inhibitors of nerve
      activity (e.g. large conductance calcium-activated potassium, BKCa, channel
      activators), tachykinin receptor antagonists, epoxygenase inducers (e.g.
      benzafibrate), inhibitors of mucin exocytosis (e.g. anti-myristoylated alanine
      rich C kinase substrate (MARCKS), peptide and Munc-18B blockers), inhibitors of
      mucin synthesis and goblet cell hyperplasia (e.g. epidermal growth factor (EGF),
      receptor tyrosine kinase inhibitors, p38 mitogen-activated protein (MAP), kinase
      inhibitors, MAP kinase kinase/extracellular signal-regulated kinase (MEK/ERK),
      inhibitors, human calcium-activated chloride (hCACL2), channel blockers and
      retinoic acid receptor-a antagonists), inducers of goblet cell apoptosis (e.g.
      Bax inducers or Bcl-2 inhibitors), and purinoceptor P(2Y2) antagonists to inhibit
      mucin secretion or P(2Y2) agonists to hydrate secretions. However, real and
      theoretical differences delineate the mucus hypersecretory phenotype in asthma
      from that in COPD. More information is required on these differences to identify
      specific therapeutic targets which, in turn, should lead to rational design of
      anti-hypersecretory drugs for treatment of airway mucus hypersecretion in asthma
      and COPD.

PMID- 16581699
TI  - Mid-term outcome after carotid artery stenting depends on presence of coronary
      artery disease.
AB  - BACKGROUND: Longer-term outcome of patients following carotid artery
      revascularization depends predominantly on cardiac events rather than
      neurological events. AIM: To assess the longer-term outcomes of patients with
      known coronary artery morphology undergoing carotid artery stenting. METHOD: In a
      prospective observational study including 549 consecutive patients undergoing
      carotid artery stenting, a coronary angiography was performed in a single session
      unless a recent angiogram was available. Following the intervention, patients
      were followed prospectively to determine neurological events as well as major
      adverse coronary events (MACE) during long-term follow-up. RESULTS: Coronary
      artery disease was present in 378 patients including 92 patients without current
      significant stenosis. The MACE rate was 6.4% in patients without coronary artery
      disease compared to 28.3% in patients with coronary artery disease (P<0.00001).
      Cardiac and all-cause mortality were statistically significantly higher in
      patients with a significant coronary stenosis than in patients without coronary
      artery disease (P<0.001 and P<0.01). Cardiac mortality and all-cause mortality
      were 2.3% and 7.6% in patients without coronary artery disease (patient group I),
      7.6% and 13.0% in patients with coronary artery disease but no current
      significant stenosis (patient group II), and 10.5% and 16.1% in patients with
      significant coronary stenosis (patient group III). Neurological events, however,
      were distributed equally among the three patient groups. CONCLUSIONS: In the
      longer term, outcomes in patients undergoing carotid artery stenting depend on
      concomitant coronary artery disease rather than neurological events, cardiac
      mortality and even all-cause mortality depending on a significant coronary artery
      stenosis.

PMID- 16581700
TI  - Human mesenchymal stem cells do not differentiate into cardiomyocytes in a
      cardiac ischemic xenomodel.
AB  - AIM: As the capability of human mesenchymal stem cells (hMSC) to engraft,
      differentiate and improve myocardial function cannot be studied in humans,
      exploration was performed in a xenomodel. METHODS: The rats were divided into
      three groups depending on the type of rats used (Rowett nude (RNU) or Fischer
      rats +/- immunosuppression). Different groups were treated with intramyocardial
      injection of hMSC (1-2 million) either directly or three days after ligation of
      the left anterior descending artery (LAD). Myocardial function was investigated
      by echocardiography. The hMSC were identified with fluorescence in situ
      hybridization and myocardial differentiation was assessed by
      immunohistochemistry. RESULTS: When hMSC were injected directly after LAD
      ligation they could be identified in half (8/16) of the RNU rats (without
      immunosuppression) at 4 weeks. When injected 3 days after LAD ligation in
      immunosuppressed RNU rats they were identified in all (6/6) rats at 6 weeks. The
      surviving hMSC showed signs of differentiation into fibroblasts. No cardiomyocyte
      differentiation was observed. There was no difference in myocardial function in
      treated animals compared to controls. CONCLUSIONS: The hMSC survived in this
      xenomodel up to 6 weeks. However, hMSC required implantation into
      immunoincompetent animals as well as immunosuppression to survive, indicating
      that these cells are otherwise rejected. Furthermore, these cells did not
      differentiate into cardiomyocytes nor did they improve heart function in this
      xenomodel.

PMID- 16581701
TI  - Lowered levels of serum albumin and HDL-cholesterol in children with a recent
      mild infection.
AB  - BACKGROUND: Infections are associated with atherogenic changes in serum.AIM. To
      elucidate effects of recent infections on risk factors for coronary heart disease
      in children. SUBJECTS AND METHODS: In 1983 and again 3 years later, 2458
      individuals aged 9, 12, 15, 18 and 21 years were investigated. In 1986, 106
      subjects had symptoms of infection during the past 2 weeks before their follow-up
      visit. Their serum albumin and lipid concentrations were compared to those in
      1983 when these individuals probably were healthy. An age- and sex-matched
      healthy control group from the cohort 1986 was chosen for comparison. For
      cholesterol age, sex and body mass index specific Z-scores in addition to actual
      values were used in statistical comparisons. RESULTS: Serum albumin was 42 g/L in
      subjects with positive history of infection and 46 g/L in healthy controls
      (P<0.0001). HDL-cholesterol and the ratio of HDL- to total cholesterol were lower
      with increasing evidence of infection. Elevated serum C-reactive protein (CRP) or
      orosomucoid grouped the subjects with high and low serum HDL-cholesterol
      concentrations better than history of infection alone. CONCLUSION: A mild
      infection lowers serum HDL-cholesterol and serum albumin concentrations, which
      both favour atherogenesis.

PMID- 16581702
TI  - New directions for psychosocial work environment research.

PMID- 16581703
TI  - Socioeconomic inequities in invasive cardiac procedures among patients with
      incident angina pectoris or myocardial infarction.
AB  - AIMS: In many countries, systematic socioeconomic disparities have emerged in the
      use of invasive cardiac procedures among myocardial infarction patients and
      hospitalized coronary patients. This study prospectively examined socioeconomic
      differences in the use of cardiac procedures in a national cohort of incident
      coronary patients. METHODS: The data were based on individual register linkages
      among 49,846 patients with incident angina pectoris (AP) or myocardial infarction
      (MI) during one-year follow-up in 1995-98 in Finland. Socioeconomic differences
      in invasive coronary procedures were examined using proportional hazard models.
      RESULTS: The analyses showed that women, AP patients, and persons with lower
      socioeconomic status received fewer procedures during the one-year follow-up than
      men, MI patients, and those with higher socioeconomic status. Socioeconomic
      differences in the utilization of cardiac procedures were similar in both AP and
      MI groups, among both men and women, and by all socioeconomic indicators: social
      class, education, and income. Disparities were already emerging after the 28-day
      follow-up among men and women in both patient groups, and they persisted
      throughout the study period. Controlling for disease severity, comorbidity, and
      hospital district did not modify the results. CONCLUSIONS: Socioeconomic
      disparities in receiving invasive coronary procedures among AP patients without
      MI were similar to those in MI patients.

PMID- 16581704
TI  - Evaluation of a sexual education intervention among Swedish high school students.
AB  - AIMS: To evaluate an intervention aimed at improving knowledge of, attitudes to,
      and practices regarding condoms and emergency contraception (ECP) among Swedish
      high school students. METHODS: An intervention study with quasi-experimental
      design. A strategic sample of classes from two vocational high school programs
      was divided into an intervention group and a comparison group. All students
      completed questionnaires before and after the intervention, which included sexual
      education lessons by a nurse-midwife and medical students, free condoms on
      request and access to telephone counseling. RESULTS: Of the 461 eligible
      students, mean age 17 years, 390 (85%) completed the pre-test and 326 (71%) the
      post-test. Three out of four (77%) had experienced sexual intercourse. The
      majority (76%) had used contraception, mostly condoms at first intercourse. The
      students already had good knowledge of condoms with no change after the
      intervention, but attitudes improved and condom use increased. Knowledge of, and
      attitudes towards ECP improved but use remained stable (29%). The most important
      source of information about ECP changed from "friends" to "school" after the
      intervention. More than one out of four (28%) had opted for free condoms but only
      3% had requested telephone counseling. CONCLUSIONS: Condom use increased after
      the intervention whereas the use of ECP remained stable. Knowledge of ECP
      improved and the attitudes towards both condoms and ECP became more positive.
      Participation of nurse-midwives and medical students, skill rehearsal, and
      improved access to condoms may be useful elements in sexual education.

PMID- 16581705
TI  - Representativity of a postal public health questionnaire survey in Sweden, with
      special reference to ethnic differences in participation.
AB  - AIM: Non-participation in health surveys is a common phenomenon. When differences
      between participants and non-participants are considerable, the external validity
      of the sample survey may decrease and false conclusions might be drawn about the
      health status of the population. For this reason, the authors aimed to
      investigate the representativity of a postal questionnaire survey performed in
      the county of Scania, Sweden, in 1999-2000. The survey, which was based on an 18-
      to 80-year-old population sample, had a 58% response rate (n = 13 604). METHODS:
      For some variables, the information obtained using the questionnaire was compared
      with information obtained from a population register that covers all the
      population in the county (for the 18- to 80-year-old group, n = 850 476). The
      population register includes, among other data, information on age, gender,
      educational level, country of birth, and healthcare expenditure. RESULTS: Men,
      individuals with a low level of education, and immigrants were under-represented
      in the survey. However, except for immigrants, the under-representation was not
      large. Among immigrants, particularly those born in former Yugoslavia, the Arabic
      speaking countries, and Poland were very significantly under-represented in the
      study. By contrast, immigrants born in other Nordic countries had responded to
      almost the same extent as respondents born in Sweden. The survey sample had about
      the same healthcare utilization costs as did the general population. CONCLUSIONS:
      In summary, the "Health Survey for Scania, 2000" seems largely representative of
      the total Scanian population. A major concern, however, is the under
      representation of the immigrant population.

PMID- 16581706
TI  - Cardiovascular risk factor burden has a stronger association with self-rated poor
      health in adults in the US than in Sweden, especially for the lower educated.
AB  - BACKGROUND: There is an ongoing debate about the importance of biomedical and
      sociodemographic risk factors in the prediction of self-rated health. OBJECTIVES:
      To compare the association of sociodemographic and cardiovascular risk factors
      and self-rated health in Sweden and the US. DESIGN: Data from two population
      based cross-sectional health surveys, one in Sweden and one in the US. SUBJECTS:
      The surveys included questionnaire and measured data from 5,461 adults in Sweden
      and 7,643 in the US. Participants were between 35 and 65 years of age. RESULTS:
      The odds ratios for poor self-rated health for the included cardiovascular risk
      factors were greater in the US. Low education was significantly more prevalent
      among those with self-rated poor health in the US, but not in Sweden. Using
      Swedes with high education as reference group (OR = 1), adults in the US with low
      education and 2+ risk factors had a greater than threefold risk (OR = 6.3) of
      self-rated poor health compared with Swedish low-educated adults with the same
      risk factor burden (OR = 1.9). The better-educated US adults with 2+ risk factors
      were significantly more likely to report poor health (OR = 3.4) compared with
      their Swedish counterparts (OR = 2.4). CONCLUSIONS: The interaction between risk
      factors, education, and self-rated health suggests a frightening picture,
      especially for the US. Public health interventions for reducing cardiovascular
      risk factors need to include both population and individual measures. Taking
      people's overall evaluation of their health into account when assessing total
      health risk is important.

PMID- 16581708
TI  - Mortality in relation to employment status during different levels of
      unemployment.
AB  - AIMS: The aim of this study was to estimate whether the risk for total and cause
      specific mortality was related to employment status, and whether mortality in
      different non-employed groups differed during high and low levels of
      unemployment. METHODS: Structured interviews were used from the Swedish Survey of
      Living Conditions in 1984-89 and 1992-97, including women and men aged 18 to 64,
      classified as unemployed (n = 2,067), retired or on temporary disability pension
      (n = 2,674), economically inactive for other reasons (n = 1,373), and employed (n
      = 38,293). Data were linked to death certificates, as registered in the Cause of
      Death Register. Cox proportional hazards models were performed for the mortality
      risk up until eight and a half years following the interview. RESULTS: Being
      unemployed (OR = 1.43), retired, or on temporary disability pension (OR = 2.28)
      or being economically inactive for other reasons (OR = 1.63) was related to a
      risk for total mortality, after considering the level of unemployment,
      sociodemographic factors and longstanding illness. The risk of death due to
      external causes was excessive among the unemployed and among those retired or on
      temporary disability pension, and resulted to a large extent from suicide. The
      interaction between employment status and level of unemployment was not
      significant. CONCLUSIONS: The level of unemployment seems to have no major
      influence on the mortality risk. Future interventions for the non-employed groups
      should focus on preventing avoidable mortality, such as injury and suicide.

PMID- 16581707
TI  - Promoting sexual and reproductive health in early adolescence in South Africa and
      Tanzania: development of a theory- and evidence-based intervention programme.
AB  - AIMS: Action to prevent the spread of HIV among young people in Sub-Saharan
      Africa is needed urgently. In order to be effective, such action should be theory
      and evidence based and carefully adapted to local cultures and contexts. The
      present article describes the organization, theoretical basis, and methodological
      approach of a project that aims at developing and evaluating school-based
      interventions targeting adolescents aged 12-14 years. METHODS: Researchers from
      European and African universities have developed interventions that were
      conducted in three sites: Cape Town and Polokwane (South Africa) and Dar es
      Salaam (Tanzania). In each site the interventions were evaluated through large
      scale field experiments with intervention schools and delayed intervention
      schools and with baseline and two follow-up data collections. Minimum sample
      sizes were estimated for each site based on local data and taking into account
      that the unit of allocation was schools and not individual students (the design
      effect). During the formative phase as well as within the field experiments,
      qualitative studies were also conducted. DISCUSSION: The interventions were
      developed consistent with the Intervention Mapping approach, and the theoretical
      framework was based on a modified version of the Theory of Planned Behaviour. The
      limitations of Western social cognition models were recognized, and the
      theoretical framework has therefore been expanded in two directions: towards
      integrating cultural processes and towards taking societal factors and
      constraints into account. CONCLUSION: The project will throw light on the
      application of social cognition models as well as the usefulness of the
      Intervention Mapping approach to intervention development in sub-Saharan Africa.

PMID- 16581709
TI  - Assessing attitude: the case of health-enhancing physical activity.
AB  - OBJECTIVES: The basic phases of constructing compact questionnaire scales for
      health-promotion interventions are demonstrated in the case of attitudes towards
      two modes of physical activity, outdoor aerobic exercise (OAE) and everyday
      commuting activity (ECA). The scales were to show good psychometric properties
      and to provide adequate indicators of attitude. METHODS: Behaviours and criteria
      were specified for both OAE and ECA. The items describing the emotional (affect)
      and cognitive (outcome-expectations) aspects of attitude towards OAE and ECA
      behaviours were selected on the basis of a pilot study. The scales under
      development were used in a Finnish population survey on health, personal
      resources and physical activity (n = 1,516). Item analyses were completed for
      purposes of refining the scale; principal component analyses and factor analyses
      were used to establish the dimensional structure of the scales. Evidence of
      discriminatory validity was provided by comparing the scale scores of the
      different groups of respondents with regular, with sub-criterion, and without any
      OAE and ECA behaviours, respectively. RESULTS: The purported psychometric
      properties were met in the case of the affective and, less obviously, the
      positive outcome-expectation scales. The negative expectation scales need to be
      reconstructed with additional items. CONCLUSIONS: The psychometric properties of
      the affective scales and the positive expectation scales allow conclusions to be
      drawn regarding group differences in attitudes towards OAE or ECA behaviours.
      These scales are ready to be cross-validated in a new sample. Test-retest
      reliability should also be established.

PMID- 16581711
TI  - Health and healthcare utilization among single mothers and single fathers in
      Sweden.
AB  - AIMS: To analyse self-rated health and healthcare utilization with regard to
      whether the respondents were single or couple parents, mothers or fathers.
      METHODS: A postal questionnaire was distributed nationwide to 4,000 randomly
      chosen individuals 20-64 years of age, with a response rate of 66%. A total of
      1,041 respondents had legal custody of a child (150 were single parents and 891
      were couple parents), and thus met the definition of a parent used for this
      study. Analyses of self-rated health and health care utilization were performed
      according to sex, age, sociodemographic, and socioeconomic characteristics. Three
      different statistical methods were applied: Spearman correlation analyses, chi
      square analyses and multivariate logistic regression. RESULTS: Both single
      fathers and single mothers reported worse health than their couple counterparts.
      However, single fathers had contact with a physician more frequently (OR 1.84)
      than couple fathers, whereas single mothers did not. Furthermore, single mothers
      refrained from seeing a physician despite a medical need much more often (OR
      2.07) than couple mothers. CONCLUSIONS: An uneven distribution of
      sociodemographic and socioeconomic characteristics might help us to understand
      why single parents, both mothers and fathers, have worse health than parents who
      live together. Previously recognized gender differences with regard to healthcare
      utilization were present in our study as well, and it is possible that these
      differences are related to the unequal distribution of sociodemographic and
      socioeconomic assets between single fathers and single mothers found here.

PMID- 16581710
TI  - "It's heavenly to be alone!": a room of one's own as a health-promoting resource
      for women. Results from a qualitative study.
AB  - AIM: This paper describes strategies developed by women to handle lack of time
      for themselves, and lack of freedom, in private life. METHODS: The paper reports
      on one self-assessed health resource identified in a larger qualitative study on
      women's paid and unpaid work and health/sickness. Twenty strategically selected
      women were interviewed, elderly women being chosen to obtain a lifetime
      perspective. The interviews were audio-taped and analysed according to a
      phenomenological approach. RESULTS: Expectations had been placed on the
      interviewees as women: to give care, always to be available for other family
      members, to adjust to their husbands. Many of them recalled seeking privacy ("a
      room of one's own") to avoid constant demands and interruptions, and as a refuge
      from partner domination. This was a conscious health-promoting strategy on their
      part. A room of one's own did not necessarily mean a physical room, but the right
      to -- and the possibility of -- a life of one's own. Forms of privacy included
      gainful employment, a separate bedroom, own social engagements. CONCLUSIONS:
      Family life still demands more from women than from men, putting many women under
      constant time pressure and without time for themselves. In heterosexual
      relationships, women frequently feel controlled. Prevailing norms for married
      women and mothers, causing blame and feelings of guilt, remain obstacles to women
      wanting "a room of their own". The health resource of having such a room, and
      strategies for creating one, should be given attention in medical research and
      practice -- not least in primary care.

PMID- 16581712
TI  - Mental health functioning (SF-36) and intentions to retire early among ageing
      municipal employees: the Helsinki Health Study.
AB  - AIMS: To examine the associations of mental health functioning with intentions to
      retire early among ageing municipal employees. METHODS: Cross-sectional survey
      data (n = 7,765) from the Helsinki Health Study in 2000, 2001, and 2002 were
      used. Intentions to retire early were sought with a question: "Have you
      considered retiring before normal retirement age?" The dependent variable was
      divided into three categories: 1 = no intentions to retire early; 2 = weak
      intentions; 3 = strong intentions. Mental health functioning was measured by the
      Short Form 36 (SF-36) mental component summary (MCS). Other variables included
      age, sex, physical health functioning (SF-36), limiting longstanding illness,
      socioeconomic status, and spouse's employment status. Multinomial regression
      analysis was used to examine the association of mental health functioning with
      intentions to retire early. RESULTS: Employees with the poorest mental health
      functioning were much more likely to report strong intentions to retire early (OR
      6.09, 95% CI 4.97-7.47) than those with the best mental health functioning.
      Adjustments for physical health, socioeconomic status, and spouse's employment
      status did not substantially affect this association. CONCLUSIONS: The findings
      highlight the importance of mental health for intentions to retire early.
      Strategies aimed at keeping people at work for longer should emphasize the
      importance of mental well-being and the prevention of poor mental health. More
      evidence is needed on why mental problems among ageing baby-boomer employees are
      giving rise to increasing social consequences, although the overall prevalence of
      mental problems has not increased.

PMID- 16581713
TI  - Combining risk factors and demographic surveillance: potentials of WHO STEPS and
      INDEPTH methodologies for assessing epidemiological transition.
AB  - AIMS: Demographic surveillance systems (DSSs) create platforms to monitor
      population dynamics. This paper discusses the potential of combining the WHO
      STEPwise approach to Surveillance (STEPS) within ongoing DSSs, to assess changes
      in non-communicable disease (NCD) risk factors. METHODS: Three DSSs in Ethiopia,
      Vietnam, and Indonesia have collected NCD risk factors using WHO STEPS, focusing
      on self-reported lifestyle risk factors (Step 1) and measurement of blood
      pressure and anthropometric parameters (Step 2). RESULTS: DSSs provide sampling
      frames for NCD risk factor surveillance, which reveals the distribution of risk
      factors and their dynamics at the population level. The WHO STEPS approach with
      its add-on modules is feasible and adaptable in DSS settings. Available mortality
      data in the DSSs enable mortality assessment by cause of death using verbal
      autopsy, which is relevant in estimating the impact of NCDs. DSSs as well as risk
      factor surveillance data may potentially be a lever for hypothesis-driven
      research to address specific a priori hypotheses or research questions.
      CONCLUSION: Combining DSSs with the WHO STEPS approach can potentially address
      basic epidemiological questions on NCDs, which can be used as a powerful advocacy
      tool in public health decision-making for NCD prevention.

PMID- 16581714
TI  - Psychosocial work conditions, unemployment, and leisure-time physical activity: a
      population-based study.
AB  - OBJECTIVE: To investigate the association between psychosocial work conditions
      and unemployment, and low leisure-time physical activity.
      DESIGN/SETTING/PARTICIPANTS/MEASUREMENTS: The 2000 public health survey in Scania
      is a cross-sectional postal questionnaire study with a 59% participation rate. A
      total of 5,180 persons aged 18-64 years who belonged to the workforce and the
      unemployed were included in this study. Logistic regression models were used to
      investigate the associations between psychosocial factors at work and
      unemployment, and low leisure-time physical activity. Psychosocial conditions at
      work were defined according to the Karasek-Theorell demand-control/decision
      latitudes into relaxed, active, passive, and job strain categories. The
      multivariate analyses included age, country of birth, education, economic stress,
      and social participation. RESULTS: In total, 16.1% of men and 14.8% of women had
      low leisure-time physical activity. The job strain (high demands/low control) and
      unemployed categories had significantly higher odds ratios of low leisure-time
      physical activity among both men and women compared with the relaxed (low
      demands/high control) reference category. However, the significant differences
      between the job strain, the unemployed, and the relaxed categories disappeared in
      the multivariate models. CONCLUSIONS: Respondents with job strain or unemployment
      have significantly higher odds ratios of low leisure-time physical activity than
      the relaxed category. However, after adjustments for education in particular the
      differences disappear. Nevertheless, the results suggest that the association
      between psychosocial work conditions, which are often dependent on education, and
      leisure-time physical activity may be interesting to study in more detail.

PMID- 16581715
TI  - East-west health divide and east-west migration: Self-reported health of
      immigrants from Eastern Europe and the former Soviet Union in Sweden.
AB  - AIM: Research on the east-west health divide has provided extensive evidence of
      poorer health in Eastern Europe and the former Soviet Union than in Western
      Europe. This study focuses on immigrants from Eastern to Western Europe and
      analyses whether they have an increased risk of self-reported poor health
      compared with the host population and what determines that. METHODS: This cross
      sectional study is based on 373 immigrants from Poland, other East European
      countries, and the former Soviet Union, aged 25-84, who arrived in Sweden after
      1944 and were interviewed during 1993-2000 along with their 35,711 Swedish
      counterparts. RESULTS: Age- and sex-adjusted unconditional logistic regression
      showed in general a 92% higher risk of reporting poor health among immigrants
      than among Swedish-born respondents. The risk also persisted after adjustment for
      several potential confounders (living singly, having a poor social network, low
      socioeconomic status, and smoking) and after an additional adjustment for
      acculturation (language at home), and years in Sweden. CONCLUSIONS: Being born in
      Eastern Europe or the former Soviet Union was an independent risk factor for
      reporting poor health. It is therefore suggested that it is important for primary
      and public care services to be aware of the health status and needs of immigrants
      from these countries.

PMID- 16581716
TI  - Spermatogenesis and sex chromosome gene content: an evolutionary perspective.
AB  - Mammalian sex chromosomes are highly diverged and heteromorphic: a comparatively
      large and gene-rich X chromosome contrasting with a small, largely
      heterochromatic and degenerate Y chromosome. Both gonosomes are however uniquely
      important in male-specific functions such as spermatogenesis. In this review, we
      examine the evolutionary pressures that have driven the divergence of the sex
      chromosomes from their ancestral state, and show how these have shaped the gene
      content of both chromosomes. Their shared history of gene acquisition and loss,
      differentiation, degeneration and intragenomic warfare has far-reaching
      consequences for their functionality in spermatogenesis, and may also have
      potential clinical implications.

PMID- 16581717
TI  - Advances and applications of germ cell transplantation.
AB  - When male germ line stem cells are transplanted from the testis of a fertile
      donor animal to the testis of an infertile recipient they can establish donor
      derived spermatogenesis in the recipient testis, and the resulting sperm can
      transmit the genotype of the donor to the offspring of the recipient. Germ cell
      transplantation provides a bioassay to study the biology of these stem cells, to
      develop systems for spermatogonial stem cell isolation and culture, to examine
      defects in spermatogenesis and to correct male infertility. Although most widely
      studied in rodents, germ cell transplantation has been applied to larger mammals,
      including primates. A potential clinical application is restoration of fertility
      in patients that underwent cytotoxic treatments for cancer. As an alternative to
      transplantation of isolated germ cells to a recipient testis, ectopic grafting of
      testis tissue from diverse mammalian donor species, including primates, into a
      mouse host represents a novel possibility to study spermatogenesis, to
      investigate the effects of toxins or drugs with the potential to enhance or
      suppress male fertility, and to produce fertile sperm from immature donors.
      Therefore, transplantation of germ cells or xenografting of testis tissue are
      uniquely valuable approaches for the study, preservation and manipulation of male
      fertility in mammalian species.

PMID- 16581718
TI  - Sperm and embryo cryopreservation practice in licensed clinics in the UK endorsed
      by The British Fertility Society.

PMID- 16581719
TI  - Fads and foibles in ART: where is the evidence?
AB  - This commentary on the scientific basis of laboratory procedures in assisted
      conception discusses the origins of widespread discrepancies in 'standard'
      laboratory techniques experienced by patients and their embryos. The lack of
      direct evidence from clinical laboratory trials and the reasons for this will be
      highlighted using some examples drawn mainly from embryo culture. Inconsistencies
      and grey areas in the governance framework of this unique field could usefully be
      eliminated and attention focused on the need for a rational approach to
      procedural trials and pilot studies necessarily conducted in clinical
      laboratories. This may help progress towards a consensus on fundamental questions
      for which the evidence is currently lacking.

PMID- 16581720
TI  - British South Asian communities and infertility services.
AB  - This paper presents key findings from the first major study of the provision of
      infertility services to South Asian communities in the UK. The research aimed to
      explore the social meanings of infertility and to examine the experiences of
      couples receiving fertility treatment. Focus groups with people from Pakistani,
      Bangladeshi and Indian communities (n = 93) revealed a strongly pro-natalist
      ideology and a relatively limited knowledge of infertility and treatments.
      Interviews with 50 participants from the same communities revealed a general
      satisfaction with secondary level infertility services. However, a minority felt
      inadequately informed about their condition, tests undertaken and treatment
      options; only one-third were given any written information about treatment; many
      were concerned about delays and waiting times; a minority felt that staff could
      be more sympathetic in their response to 'failed' treatment and several couples
      suggested that additional emotional support would be helpful. No information or
      resources were available in any South Asian language and the arrangements for
      communication support for non-English speakers were generally less than adequate.
      There was little evidence of the use of data on ethnic or religious background in
      infertility clinics. Recommendations for policy and practice are proposed.

PMID- 16581721
TI  - Investigation of infertility management in primary care with open access
      hysterosalpingography (HSG): a pilot study.
AB  - Infertility affects one in seven couples in the United Kingdom. The National
      Institute for Clinical Excellence (NICE) issued guidance on the management of the
      infertile couple in February 2004, which included the statement "for the
      assessment of tubal damage, women not known to have co-morbidities (pelvic
      inflammatory disease, endometriosis or previous ectopic pregnancy) should be
      offered hysterosalpingography (HSG)". We made HSG available to six general
      practices in Newcastle upon Tyne as an open access investigation. Our aim was to
      evaluate the uptake of open access HSG, speed of access to specialist services
      and the quality of the information recorded in the referral letter. Using
      hospital clinical records we tracked the outcome of all infertile couples from
      the six pilot practices over a nine-month period. Of the 39 referrals identified,
      10 women were eligible for open access HSG, of which six HSGs were organized by
      GPs. Couples who had open access HSG reached a diagnosis and management plan four
      weeks earlier than those who were referred directly (mean difference 4.0 weeks,
      95% confidence interval (CI) -8.8 to 0.4 weeks). The information recorded in the
      referral letter was generally poor. However, all referrals made via the open
      access HSG service had the prerequisite tests done. Open access HSG allowed
      prompter access to specialist services with more complete information passed on
      in the referral letter. Open access HSG was used in 15% of all infertile couples
      and 60% of those who fitted the criteria for its use. Open access HSG together
      with semen analysis and endocrine blood tests may allow GPs to manage the initial
      stages of the infertile couple and make a diagnosis.

PMID- 16581722
TI  - Molecular screening of CFTR gene in Brazilian men with bilateral agenesis of the
      vas deferens.
AB  - Infertility is a common symptom of cystic fibrosis, especially in men (95% become
      sterile). It is caused by blockage of the vas deferens and the epididymis, which
      result in degeneration of the tubules. The purpose of this study was to verify
      the frequency of CFTR gene mutation in patients with bilateral agenesis of the
      vas deferens using SSCP and sequencing. The study population consisted of 40
      white individuals with agenesis of the vas deferens as well as their 12 siblings
      without agenesis of the vas deferens. CTFR gene mutation was found in 22 of the
      40 patients (55%) and it was possible to detect both mutating alleles in these 22
      patients. The most frequent genotype found was ?F508/IVS8-5T. There was no
      genotype concordance in siblings. Our results show the importance of the
      investigation of CFTR mutation in patients with vas deferens agenesis.

PMID- 16581728
TI  - Recreational drug use and sexual risk practice among men who have sex with men in
      the United Kingdom.

PMID- 16581729
TI  - Evaluating novel interventions for chlamydia screening.

PMID- 16581730
TI  - Reflections of a president.

PMID- 16581733
TI  - Progressive symptoms and signs following institution of highly active
      antiretroviral therapy and subsequent antituberculosis therapy: immune
      reconstitution syndrome or infection?
AB  - A 36 year old man presented with weight loss, cough, fever, and exertional
      dyspnoea shortly after a diagnosis of HIV infection. Symptoms and initial
      radiological abnormalities worsened after highly active antiretroviral therapy
      was started. An eventual diagnosis was established but multiple problems occurred
      throughout the treatment period. Differentiation between immune reconstitution
      inflammatory syndrome and an infective cause was problematic.

PMID- 16581731
TI  - Male circumcision and risk of syphilis, chancroid, and genital herpes: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: Male circumcision is associated with reduced risk of HIV infection.
      This may be partly because of a protective effect of circumcision on other
      sexually transmitted infections (STI), especially those causing genital ulcers,
      but evidence for such protection is unclear. Our objective was to conduct a
      systematic review and meta-analyses of the associations between male circumcision
      and infection with herpes simplex virus type 2 (HSV-2), Treponema pallidum, or
      Haemophilus ducreyi. METHODS: Electronic databases (1950-2004) were searched
      using keywords and text terms for herpes simplex, syphilis, chancroid, ulcerative
      sexually transmitted diseases, or their causative agents, in conjunction with
      terms to identify epidemiological studies. References of key articles were hand
      searched, and data were extracted using standardised forms. Random effects models
      were used to summarise relative risk (RR) where appropriate. RESULTS: 26 articles
      met the inclusion criteria. Most syphilis studies reported a substantially
      reduced risk among circumcised men (summary RR = 0.67, 95% confidence interval
      (CI) 0.54 to 0.83), although there was significant between study heterogeneity (p
      = 0.01). The reduced risk of HSV-2 infection was of borderline statistical
      significance (summary RR = 0.88, 95% CI 0.77 to 1.01). Circumcised men were at
      lower risk of chancroid in six of seven studies (individual study RRs: 0.12 to
      1.11). CONCLUSIONS: This first systematic review of male circumcision and
      ulcerative STI strongly indicates that circumcised men are at lower risk of
      chancroid and syphilis. There is less association with HSV-2. Potential male
      circumcision interventions to reduce HIV in high risk populations may provide
      additional benefit by protecting against other STI.

PMID- 16581734
TI  - Sexual behaviour, condom use, and disclosure of HIV status in HIV infected
      heterosexual individuals attending an inner London HIV clinic.
AB  - BACKGROUND: The National Strategy for Sexual Health and HIV for England (2001)
      emphasised the role of HIV services in reducing secondary transmission of HIV
      through prevention work with HIV infected people. OBJECTIVE: To determine the
      sexual behaviour, condom use, and disclosure of HIV status of HIV infected
      heterosexuals attending an inner London HIV clinic. DESIGN: Cross sectional
      questionnaire study of heterosexual HIV infected individuals attending an HIV
      outpatient clinic. METHODS: We collected demographic data for all respondents and
      sexual behaviour data for those sexually active over the past year using a self
      administered questionnaire. Viral load and CD4 count for responders and age, sex,
      ethnicity, viral load, and CD4 count for non-responders were obtained from the
      clinic database. RESULTS: The response rate was 47.3% (n = 142). 100 participants
      reported being sexually active in the past year, of whom 73% used condoms when
      they last had vaginal sex. Knowledge of partner's HIV status was the only
      variable significantly associated with the participant disclosing their HIV
      status to their partner (p<0.001). In those who had disclosed their status, only
      knowledge of partner's HIV status was significantly associated with condom use (p
      = 0.03). CONCLUSIONS: Issues relating to non-disclosure and partner notification
      in HIV infected heterosexuals will need to be better understood to improve sexual
      health in this group and to reduce onward transmission of HIV.

PMID- 16581737
TI  - The HIV related risks among men having sex with men in rural Yunnan, China: a
      qualitative study.
AB  - OBJECTIVES: To explore the characteristics and issues specific to HIV related
      risk behaviours among men who have sex with men (MSM) in rural China. METHOD:
      Qualitative study using semistructured in-depth interviews in Dali prefecture,
      Yunnan. 24 informants recruited through a local MSM network, snowballing and by
      word of mouth. The main outcome measures were themes identified as increased
      exposures and risks to HIV. RESULTS: Risk behaviour, social stigma, one child
      policy and concepts of traditional Chinese medicine (TCM) had significant roles
      in the spread of HIV in rural China. Many MSM lead a life with double identities
      in China and condom use was found to be variable with attempts to "rationalise"
      the risky behaviour being its major determining factor. Health seeking behaviours
      of genitourinary problems were infrequent and illogical, which were further held
      back by the existing healthcare system and lack of sensitivity expressed by the
      health professionals. CONCLUSIONS: Clear education messages to the general public
      while raising awareness among health professionals of the health risks and needs
      in MSM are essential in the prevention of the current HIV epidemic.

PMID- 16581736
TI  - High rates of syphilis among STI patients are contributing to the spread of HIV-1
      in India.
AB  - BACKGROUND: Recent syphilis outbreaks have raised concern regarding the potential
      enhancement of HIV transmission. The incidence of syphilis and its association
      with HIV-1 infection rates among a cohort of sexually transmitted infection (STI)
      clinic attendees was investigated. METHODS: 2732 HIV-1 seronegative patients
      attending three STI and one gynaecology clinic, were enrolled from 1993-2000 in
      an ongoing prospective cohort study of acute HIV-1 infection in Pune, India. At
      screening and quarterly follow up visits, participants underwent HIV-1 risk
      reduction counselling, risk behaviour assessment and HIV/STI screening that
      included testing for serological evidence of syphilis by RPR with TPHA
      confirmation. Patients with genital ulcers were screened with dark field
      microscopy. RESULTS: Among 2324 participants who were HIV-1 and RPR seronegative
      at baseline, 172 participants were found to have clinical or laboratory evidence
      of syphilis during follow up (5.4 per 100 person years, 95% CI 4.8 to 6.5 per 100
      person years). Independent predictors of syphilis acquisition based on a Cox
      proportional hazards model included age less than 20 years, lack of formal
      education, earlier calendar year of follow up, and recent HIV-1 infection. Based
      on a median follow up time of 11 months, the incidence of HIV-1 was 5.8 per 100
      person years (95% CI 5.0 to 6.6 per 100 person years). Using a Cox proportional
      hazards model to adjust for known HIV risk factors, the adjusted hazard ratio of
      HIV-1 infection associated with incident syphilis was 4.44 (95% CI 2.96 to 6.65;
      p<0.001). CONCLUSIONS: A high incidence rate of syphilis was observed among STI
      clinic attendees. The elevated risk of HIV-1 infection that was observed among
      participants with incident syphilis supports the hypothesis that syphilis
      enhances the sexual transmission of HIV-1 and highlights the importance of early
      diagnosis and treatment of syphilis.

PMID- 16581738
TI  - Methamphetamine and sildenafil (Viagra) use are linked to unprotected receptive
      and insertive anal sex, respectively, in a sample of men who have sex with men.
AB  - OBJECTIVES: There is evidence that methamphetamine and sildenafil (Viagra) use
      are associated with sexual risk behaviour among men who have sex with men (MSM).
      We investigated the association of methamphetamine, sildenafil, and other
      substance use with unprotected receptive and insertive anal sex among MSM by
      conducting an encounter specific analysis. METHODS: Data were from a cross
      sectional, community based survey of MSM in San Francisco regarding behaviour
      during their most recent anal sex encounter. Mulitvariate regression analysed
      independent associations of specific substance use and demographic variables with
      unprotected anal sex behaviours. RESULTS: The sample (n = 388) was diverse in
      race/ethnicity, age, income, education, HIV status, and homosexual/bisexual
      identification. More than half (53%) reported unprotected anal sex, including
      insertive (29%) and receptive (37%) during their most recent anal sex encounter;
      12% reported unprotected insertive and 17% reported unprotected receptive anal
      sex with an HIV discordant or unknown partner. Methamphetamine was used by 15%
      and sildenafil was used by 6% of the men before or during the encounter; 2% used
      both drugs. In multivariate analysis controlling for demographic factors and
      other substance use, methamphetamine use was associated with unprotected
      receptive (odds ratio (OR), 2.03; 95% confidence interval (CI), 1.09 to 3.76) and
      sildenafil use was associated with unprotected insertive (OR, 6.51; CI, 2.46 to
      17.24) anal sex. Effects were stronger with HIV discordant or unknown sex
      partners specifically. CONCLUSION: Encounter specific associations of
      methamphetamine and sildenafil use with unprotected receptive and insertive anal
      sex, respectively, indicate the importance of assessment specificity and
      tailoring risk reduction efforts to address certain drugs and sexual behavioural
      roles among MSM.

PMID- 16581739
TI  - Understanding male sexual behaviour in planning HIV prevention programmes:
      lessons from Laos, a low prevalence country.
AB  - METHODS: Focus group discussions were conducted with a range of young men in
      Vientiane, Laos; interviews were conducted with male sex workers. A questionnaire
      survey was conducted with a purposive sample of 800 young men. RESULTS: Most
      young men initiate sex at an early age and have multiple sex partners. Married
      men are more likely to pay for sex and most sex for money is negotiated in non
      brothel settings. Despite high reported condom use for last intercourse with a
      casual partner, decisions on condom use are subjective. Many men have
      extramarital sex when their partner is pregnant and post partum. 18.5% of men
      report having had sex with another man; most of these men also report having sex
      with women. Moreover, more men report having had anal sex with a woman than with
      a man. CONCLUSIONS: Although not a probability sample survey, this study of a
      broad range of young men in Vientiane reveals sexual behaviours that could lead
      to accelerated HIV transmission. Education should emphasise the need to use
      condoms in all sexual encounters outside the primary relationship. This needs
      special emphasis when the partner is pregnant or post partum. Advice on safe sex
      with other men needs to be integrated into all sexual health education for young
      men.

PMID- 16581740
TI  - The potential role of serology in diagnosing chronic lymphogranuloma venereum
      (LGV): a case of LGV mimicking Crohn's disease.
AB  - We present the case of a 26 year old HIV positive homosexual man who was managed
      for suspected Crohn's disease for over 1 year before lymphogranuloma venereum
      (LGV) was clinically diagnosed. He had presented with constipation, secondary to
      acute haemorrhagic proctitis, and subsequently had two chlamydia negative rectal
      smears, using direct fluorescent antibody (DFA) Chlamydia trachomatis staining.
      Positive chlamydial serology guided retrospective testing of an early rectal
      biopsy, which was found to have C trachomatis by polymerase chain reaction (Roche
      Cobas) and identified as LGV serovar L2 by the Sexually Transmitted Bacteria
      Reference Laboratory (STBRL), Health Protection Agency (HPA), Colindale, London.
      Chlamydial serology may have a role in identifying late stage LGV infection.
      Although no standardised test currently exists, consideration should be given to
      evaluating the role of chlamydial serology in establishing a diagnosis of LGV.

PMID- 16581742
TI  - Simplifying chlamydia testing: an innovative Chlamydia trachomatis testing
      approach using the internet and a home sampling strategy: population based study.
AB  - OBJECTIVES: To measure the coverage, gender distribution, and participants'
      prevalence of genital Chlamydia trachomatis infections using a new internet based
      self selective testing approach by means of home sampling in the general
      population in Sweden. To investigate factors associated with these measures.
      METHODS: Observational survey of people actively ordering coded testing packages,
      and checking their test results, from a known website. No personal invitations
      were sent out. All inhabitants (256 885 men and women) in a Swedish county were
      eligible to participate. A special interest was taken in coverage, gender
      distribution, participants' chlamydia prevalence, and determinants for infection.
      RESULTS: Testing was highest in the age group 20-24 years, where 298/9495 (3.1%)
      of all women and 171/9574 (1.8%) of all men in the population participated. The
      overall population participation (all ages) was 906/256 885 (0.4%). 40% (364/906)
      of the tests were from men and 60% (542/906) from women. The prevalence of
      Chlamydia trachomatis infection was 6.0% (95% CI: 3.6% to 8.4%) among male
      participants and 4.6% (95% CI: 2.8% to 6.4%) among female participants.
      Prevalence increased with decreasing age. Believing to be infected and having
      symptoms were the strongest determinants of infection. CONCLUSION: Simplifying
      and increasing the accessibility of chlamydia testing by means of internet and
      home sampling proved feasible. Self risk assessment improves the chance of
      finding people infected by Chlamydia trachomatis, especially among men, if an
      accessible testing method is offered. This new method can serve as a supplement
      to regular preventive methods and might encourage young people to be tested.

PMID- 16581743
TI  - Chlamydia trachomatis infections in multi-ethnic urban youth: a pilot combining
      STI health education and outreach testing in Rotterdam, Netherlands.
AB  - BACKGROUND/OBJECTIVES: Testing for Chlamydia trachomatis (Ct) is less accepted in
      people of non-Dutch ethnicity than Dutch people. We offered additional Ct and
      gonorrhoea testing through our outreach sexually transmitted infections (STI)
      prevention programme to determine whether this intervention strategy is feasible
      and efficient. METHODS: Outreach workers offered test kits to women and men aged
      15-29 years, in group and street settings and in a vocational training school.
      Demographic and behavioural data and characteristics of non-responders were
      assessed. DNA was isolated (using the MagNA Pure LC system) from urine and tested
      using the Cobas Amplicor test. RESULTS: Among sexually active people, the test
      rate differed by venue (groups 80% (74/93), school 73% (49/67), street 17%
      (49/287); p<0.001). There was no difference in test rate between group and school
      settings by gender or ethnicity. Ct positivity was 14.5% (25/172); women 20.2%
      (20/99) versus men 6.8% (5/73); p = 0.01. Ct positivity was highest at school
      (24.5% (12/49)) and among Surinamese/Antillean people (17.5% (14/80)). Treatment
      rate of index cases and current partners was 100% and 78%, respectively.
      CONCLUSIONS: We found a high acceptance of chlamydia testing in group and school
      settings in both men and women of non-Dutch ethnicity. The prevalence indicates
      that we have accessed high risk people. Outreach testing and is feasible and most
      efficient in school and group settings. School screening may have an impact on
      community prevalence of Ct infections.

PMID- 16581745
TI  - The psychosocial impact of serological diagnosis of asymptomatic herpes simplex
      virus type 2 infection.
AB  - OBJECTIVES: To evaluate the impact of a positive herpes simplex virus type 2 (HSV
      2) serological test on psychosocial functioning among people with no known
      history of genital herpes. METHODS: Individuals (age 14-30 years) without a
      history of genital herpes were recruited from an urban university setting and
      sexually transmitted diseases (STD), primary care, and adolescent clinics.
      Participants completed a questionnaire addressing psychological functioning,
      psychosocial adjustment, and perceived quality of sex and were offered free HSV-2
      antibody testing. 33 HSV-2 positive people and 60 HSV-2 negative people
      demographically matched from the same source of recruitment were re-evaluated at
      a 3 month follow up visit. HSV-2 positive participants also completed a genital
      herpes quality of life (GHQOL) measure. RESULTS: Of the 33 who were HSV-2
      seropositive, four did not recall their diagnosis. In comparing those who were
      HSV-2 positive with those who were negative, repeated measures analysis of
      variance indicated there were no significant differences over time on any of the
      measures. None the less, many HSV-2 positive individuals indicated that the
      diagnosis had a notable impact on their quality of life. Also, among the HSV-2
      positive people, lower GHQOL at the 3 month follow up was predicted by higher
      interpersonal sensitivity (r = -0.44, p<0.05), lower social support (r = 0.40,
      p<0.05), and quality of sex (r = 0.62, p<0.01) at baseline. CONCLUSIONS: A
      diagnosis of asymptomatic HSV-2 infection does not appear to cause significant
      lasting psychological difficulties. Those for whom the diagnosis had the greatest
      impact were interpersonally vulnerable before the diagnosis. These results
      suggest that assessment of interpersonal distress may be important to include as
      part of pretest and post-test counselling.

PMID- 16581747
TI  - Type specific seroprevalence of HSV-1 and HSV-2 in four geographical regions of
      Poland.
AB  - OBJECTIVE: To examine the type specific seroprevalence of herpes simplex virus
      (HSV) types 1 and 2 infections, stratified by age and gender, and associated risk
      factors for HSV-2 seropositivity in Poland. METHODS: 2257 serum samples of
      individuals from 15-65 years were randomly selected from serum banks in four
      different geographical regions of Poland, including the Zachodnio-pomorskie,
      Warminsko-mazurskie, Lubelskie, and Mazowieckie districts. Type specific serum
      antibodies to HSV-1 and HSV-2 were detected using HerpeSelect IgG ELISA tests.
      RESULTS: Overall prevalences of type specific HSV-1 and HSV-2 serum antibodies
      were 90.4% and 9.3%, respectively. Age standardised HSV-2 seroprevalence was
      higher in women (9.7%) than men (8.8%) (p = 0.06), and increased notably with age
      from 4% in 15-24 year olds to 12% in those aged 50-65 years. HSV-1 seroprevalence
      was consistently higher than HSV-2 seroprevalence in each specific age group,
      ranging from 74.5% in 15-24 year olds to 98.8% in 50-65 year olds. HSV-2
      seroprevalence varied significantly by geographical region, with the highest
      prevalence in the Zachodnio-pomorskie district (12%). Significant multivariate
      risk factors for HSV-2 seropositivity included older age, female gender, and
      geographical place of residence. CONCLUSION: This large survey found a notably
      high seroprevalence of HSV-1, even among young female adolescents 15-19 years of
      age (80%). HSV-2 seropositivity was under 12% in all age groups surveyed in
      Poland, tending to be among the lowest overall HSV-2 seropositivity rates
      reported thus far in Europe.

PMID- 16581748
TI  - Prevalence of infection with herpes simplex virus types 1 and 2 in Australia: a
      nationwide population based survey.
AB  - BACKGROUND: Studies demonstrating previous herpes simplex virus (HSV) type 2
      infection as a risk factor for HIV transmission, and the development of a HSV
      vaccine candidate, have emphasised the need for worldwide population based
      studies of HSV seroprevalence. The only nationwide seroprevalence studies have
      been conducted in the United States. METHODS: An Australia-wide, population based
      study of HSV-1 and HSV-2 seroprevalence was conducted, using serum and
      sociodemographic data collected between 1999-2000, for a representative study of
      risk factors for diabetes in over 11 000 adults. A stratified random sample of
      4000 was tested for HSV-2 and 1000 for HSV-1, with sampling and weighting for
      various demographic factors. RESULTS: Seroprevalence of HSV-2 in Australian
      adults was 12%. Prevalence in women (16%) was twice that in men (8%). Rural
      populations had a lower prevalence (9%) than metropolitan (13%), and Indigenous
      had a higher prevalence (18%) than the non-Indigenous populations (12%). The
      seroprevalence of HSV-1 was 76% with significant differences by age group, sex
      and Indigenous status. CONCLUSION: These are the first nationwide data to compare
      with US studies. HSV-2 infection is less common in Australia than the United
      States, and this will allow planning for combating HIV transmission in high
      prevalence populations in northern Australia. In addition, the high HSV-1
      seroprevalence will be important for future deployment of genital herpes
      vaccines.

PMID- 16581749
TI  - Social and psychological impact of HPV testing in cervical screening: a
      qualitative study.
AB  - OBJECTIVE: Human papillomavirus (HPV) testing has been proposed for inclusion in
      the UK cervical screening programme. While testing may bring some benefits to the
      screening programme, testing positive for HPV, a sexually transmitted virus, may
      have adverse social and psychological consequences for women. The aim of this
      study was to examine the social and psychological impact of HPV testing in the
      context of cervical cancer screening. METHOD: In-depth interviews generating
      qualitative data were carried out with 74 women participating in HPV testing in
      England between June 2001 and December 2003. Purposive sampling was used to
      ensure heterogeneity in age, ethnic group, marital status, socioeconomic
      background, cytology, and HPV results among participants. RESULTS: Testing
      positive for HPV was associated with adverse social and psychological
      consequences, relating primarily to the sexually transmitted nature of the virus
      and its link to cervical cancer. Women described feeling stigmatised, anxious and
      stressed, concerned about their sexual relationships, and were worried about
      disclosing their result to others. Anxiety about the infection was widespread,
      but the impact of testing positive varied. The psychological burden of the
      infection related to women's relationship status and history, their social and
      cultural norms and practices around sex and relationships, and their
      understanding of key features of HPV. CONCLUSION: HPV testing should be
      accompanied by extensive health education to inform women and to de-stigmatise
      infection with the virus to ensure that any adverse impact of the infection on
      women's wellbeing is minimised.

PMID- 16581750
TI  - Identification of chlamydia and gonorrhoea among women in rural Haiti: maximising
      access to treatment in a resource poor setting.
AB  - OBJECTIVE: To develop a risk assessment algorithm that will increase the
      identification and treatment of women with cervical infection in rural Haiti.
      METHODS: Study participants were randomly selected from new patients who accessed
      services at a women's health clinic in rural Haiti between June 1999 and December
      2002. This case-control study included women who tested positive for chlamydia
      and/or gonorrhoea based on the Gen-Probe PACE 2 laboratory test as cases.
      Controls were women who tested negative for both of these infections. RESULTS:
      Women from this area of rural Haiti had a limited level of education and lived in
      impoverished housing conditions. The sensitivity estimates of Haitian Ministry of
      Health and WHO algorithms for detecting chlamydia and/or gonorrhoea were
      generally low (ranging from 16.1% to 68.1%) in this population. Risk scores based
      on logistic regression models of local risk factors for chlamydia and gonorrhoea
      were developed and sensitivity estimates were higher for algorithms based on
      these risk scores (up to 98.8%); however, specificity was compromised.
      CONCLUSIONS: A risk assessment algorithm to identify women with chlamydia and/or
      gonorrhoea is more sensitive and less specific than the syndromic management
      approach advocated by WHO and adapted by the Haitian Ministry of Health. Using a
      risk assessment tool with high sensitivity based on local risk factors of
      cervical infection will maximise access to care, improve outcomes, and decrease
      morbidity in women who have cervical infection in rural Haiti.

PMID- 16581751
TI  - Antimicrobial self medication for reproductive tract infections in two provinces
      in Lao People's Democratic Republic.
AB  - OBJECTIVES: To describe antimicrobial self medication for reproductive tract
      infections (RTI) including sexually transmitted infections (STI), and to explore
      the understanding and use of health information among the adult population self
      medicating with antimicrobials for RTI/STI in two provinces of Laos. This could
      contribute to quality improvement of RTI/STI management. METHODS: Cross sectional
      community based study. Structured interviews (household survey) were conducted
      among 500 subjects aged 18 or more, who had used antimicrobials as self
      medication for RTI/STI during the past year. They were recruited among 3056
      family members in Vientiane capital and Champasak province, divided equally
      between the two study sites, and between urban and rural areas. RESULTS: Among
      the 500 respondents reporting self medication for RTI/STI, 91% had bought the
      antimicrobials from local private pharmacies without a physician's prescription.
      58% of those were advised to buy the drugs from drug sellers. Ampicillin (not
      recommended as syndromic treatment for RTI/STI) was used in 83% of all cases, in
      28% combined with tetracycline. 79% of respondents used antimicrobials for a non
      recommended duration of time. Most respondents had access to health messages for
      RTI/STI, largely from radio/television and drug sellers. However, only 17% of all
      respondents reported that they had ever used a condom. CONCLUSIONS: More than
      three quarters of respondents, self medicating for RTI/STI with antimicrobials,
      used inappropriate drugs bought from private pharmacies. There is a need to
      improve RTI/STI management, including health promotion, through interventions at
      community level, and to health providers, including private drug sellers.

PMID- 16581752
TI  - Unusual cause of acute scrotal cellulitis in an HIV positive man.

PMID- 16581754
TI  - Understanding the reasons for decline of HIV prevalence in Haiti.
AB  - OBJECTIVES: HIV sero-surveillance rounds and projection estimates suggest a
      decline of HIV prevalence among pregnant women and the general population in
      Haiti. This study aimed to evaluate the decline of HIV prevalence and understand
      the reasons for the decline. METHODS: Following an epidemiological analysis,
      three mathematical models were used to re-create the national epidemic, calculate
      HIV incidence, and confirm the decline of HIV prevalence. Declining trends in
      prevalence data were compared with observed trends in behavioural data. RESULTS:
      HIV progressed rapidly from initial infection to AIDS and death, with people
      dying twice as fast as in developed countries. With the rapid progression of the
      disease and the early intervention efforts in securing the blood supply,
      prevalence among commercial sex workers and blood donors peaked in the late 1980s
      followed by a decline in the mid-1990s in the general population. The observed
      decline among pregnant women and in the general population was confirmed after
      controlling for confounding variables. The Haitians are well informed: there is
      an increase in condom use with occasional partners at last contact and in
      abstinence and fidelity, and a decrease in the number of occasional partners.
      However, the age of sexual debut is lower and the proportion of sexually active
      youth has increased. CONCLUSIONS: There is evidence of decline in HIV prevalence
      among pregnant women, specifically among pregnant women living in urban areas and
      pregnant women 25 years and older, but not among pregnant women living in rural
      areas and pregnant women 24 years and younger. Although many factors have acted
      in synergy to halt the AIDS epidemic in Haiti, the main reasons for decline seem
      to point to mortality and blood safety intervention efforts in the early stages
      of the epidemic.

PMID- 16581753
TI  - Declines in HIV prevalence can be associated with changing sexual behaviour in
      Uganda, urban Kenya, Zimbabwe, and urban Haiti.
AB  - OBJECTIVE: To determine whether observed changes in HIV prevalence in countries
      with generalised HIV epidemics are associated with changes in sexual risk
      behaviour. METHODS: A mathematical model was developed to explore the relation
      between prevalence recorded at antenatal clinics (ANCs) and the pattern of
      incidence of infection throughout the population. To create a null model a range
      of assumptions about sexual behaviour, natural history of infection, and sampling
      biases in ANC populations were explored to determine which factors maximised
      declines in prevalence in the absence of behaviour change. Modelled prevalence,
      where possible based on locally collected behavioural data, was compared with the
      observed prevalence data in urban Haiti, urban Kenya, urban Cote d'Ivoire,
      Malawi, Zimbabwe, Rwanda, Uganda, and urban Ethiopia. RESULTS: Recent downturns
      in prevalence observed in urban Kenya, Zimbabwe, and urban Haiti, like Uganda
      before them, could only be replicated in the model through reductions in risk
      associated with changes in behaviour. In contrast, prevalence trends in urban
      Cote d'Ivoire, Malawi, urban Ethiopia, and Rwanda show no signs of changed sexual
      behaviour. CONCLUSIONS: Changes in patterns of HIV prevalence in urban Kenya,
      Zimbabwe, and urban Haiti are quite recent and caution is required because of
      doubts over the accuracy and representativeness of these estimates. Nonetheless,
      the observed changes are consistent with behaviour change and not the natural
      course of the HIV epidemic.

PMID- 16581756
TI  - Current trends in Rwanda's HIV/AIDS epidemic.
AB  - OBJECTIVE: To review the trajectory of Rwanda's HIV epidemic, including long term
      trends and more recent trends in HIV prevalence, markers of HIV incidence, and
      behavioural indicators. METHODS: This paper reviews the history of HIV
      serological and behavioural surveillance efforts in Rwanda, dating back to the
      early 1980s, synthesising findings from surveillance, research, and other
      relevant HIV programmatic data. The documentation reviewed includes published
      findings, conference abstracts, and unpublished analyses. Special emphasis is
      given to more recent sentinel surveillance results and data collected using
      known, documented methods. Recent trends in HIV prevalence were assessed among
      sites participating in the three most recent consecutive rounds of antenatal
      clinic sentinel surveillance. RESULTS: Early HIV surveillance in Rwanda
      documented high HIV prevalence in urban areas with HIV widely disseminated into
      rural areas by 1986. Between 1988 and 1996, HIV prevalence among pregnant women
      ranged from 21% to 33% in Kigali, from 8% to 22% in other urban settings, and
      from 2% to 12% in rural settings. More recent surveillance among pregnant women
      has demonstrated more moderate prevalence, with urban/rural differences narrowing
      slightly. Between 1998 and 2003, HIV prevalence may have declined in urban areas,
      whereas rural areas appear to have remained stable. Age at first sexual
      intercourse is relatively late in Rwanda (20 years for both males and females)
      and has remained stable since at least 1992. CONCLUSIONS: The present analysis
      suggests that Rwanda may have experienced declines over the long term in HIV
      prevalence in urban areas, especially in Kigali, and may have stable or slightly
      rising HIV prevalence in rural areas. The limited behavioural data available
      suggest that, on the national level, Rwanda may benefit from a unique combination
      of low numbers of partners and late sexual debut, which may have had a mitigating
      effect on HIV prevalence.

PMID- 16581755
TI  - Evidence for population level declines in adult HIV prevalence in Kenya.
AB  - The HIV/AIDS epidemic in Kenya has been tracked through annual sentinel
      surveillance in antenatal clinics since 1990. The system started with 13 sites
      and now has over 35. Behaviours have been measured through national Demographic
      and Health Surveys in 1993, 1998, and 2003. The surveillance data indicate that
      prevalence has declined substantially starting in 1998 in five of the original 13
      sites and starting in 2000 in another four sites. No decline is evident in the
      other five original sites although the 2004 estimate is the lowest recorded.
      Nationally, adult prevalence has declined from 10% in the late 1990s to under 7%
      today. Surveys indicate that both age at first sex and use of condoms are rising
      and that the percentage of adults with multiple partners is falling. It is clear
      that HIV prevalence is now declining in Kenya in a pattern similar to that seen
      in Uganda but seven or eight years later. Although the coverage of preventive
      interventions has expanded rapidly since 2000 this expansion was too late to
      account for the beginnings of the decline in prevalence. More work is needed to
      understand fully the causes of this decline, but it is encouraging to see Kenya
      join the small list of countries experiencing significant declines in HIV
      prevalence.

PMID- 16581757
TI  - HIV/AIDS in Ethiopia: where is the epidemic heading?
AB  - OBJECTIVES: A possible decline in prevalence of HIV in some sub-Saharan African
      countries has been reported recently. The present study aimed to evaluate the
      prevalence and incidence of HIV and behavioural data to investigate trends in
      HIV/AIDS in Ethiopia. METHODS: A review was conducted of published reports and
      literature, raw and modelled (using Epidemic Projection Package and Spectrum
      software) surveillance data and estimates from antenatal clinics (ANCs) and data
      from voluntary counselling and testing centres. Observations were restricted to
      the adult population. RESULTS: Between 2001 and 2003, more ANC sites showed a
      decline than a rise in HIV prevalence, but most lacked statistical significance.
      Modelled data suggested a rise in prevalence of HIV in rural areas (2003: 2.6%)
      and in all Ethiopia (2003: 4.4%), but a stable or declining prevalence in Addis
      Ababa (2003: 14.6%) and other urban areas (2003: 11.8%). Modelled HIV incidence,
      inferred from prevalence changes, showed a slowly rising trend in Addis Ababa
      (2003: 2.0%), other urban areas (2003: 1.7%), and rural Ethiopia (2003: 0.46%).
      The total burden of HIV/AIDS is expected also to rise substantially due to
      population growth. In Addis Ababa, crude data on HIV prevalence from ANCs too
      suggested a falling trend. Voluntary counselling and testing data from 2002 to
      2004 supported this trend but indicated a mixed trend pattern for high risk
      behaviour. No other serial behavioural trend data were available. CONCLUSIONS:
      Lack of quality data on behavioural trends impedes the interpretation of
      prevalence and incidence data in Ethiopia. Modelled data suggest an expanding HIV
      epidemic in rural and all Ethiopia, but a possible decline in some urban areas.
      Crude site prevalence values may be more sensitive to acute changes, possibly
      indicating a slowing/reversal of the epidemic's expansion.

PMID- 16581758
TI  - Trends in antenatal HIV prevalence in urban Uganda associated with uptake of
      preventive sexual behaviour.
AB  - BACKGROUND: Epidemiological surveillance in Uganda has consistently shown
      declining HIV prevalence particularly among young antenatal women since the early
      1990s, correlated with increased uptake of protective sexual behaviour.
      OBJECTIVE: To describe trends in sexual behaviour nationwide and antenatal HIV
      prevalence from urban sentinel sites in Uganda (1989-2002). METHODS: Review of
      antenatal HIV seroprevalence data from the sentinel surveillance system (1989
      2002) and data on sexual behavioural indicators from the AIDS module of the
      National Demographic and Health Surveys (1989, 1995 and 2000/01). Trends in
      biological and behavioural indicators assessed. RESULTS: Antenatal HIV
      seroprevalence in seven urban clinics peaked around 1992 (15-30%) followed by a
      steady decline by 2002 (5-12%), most markedly among women aged 15-19 and 20-24
      years. This coincided with increased primary and secondary abstinence among young
      people nationwide. Median age at sexual debut increased from 16.5 in 1989 to 17.3
      in 2000 for women and from 17.6 in 1995 to 18.3 in 2000 for men. Premarital sex
      among women and multiple partnerships decreased between 1995 and 2000. There were
      no significant changes in reporting of extramarital sex among men. Ever use of
      condoms increased from 1% among women in 1989 and 16% among men in 1995 to 16%
      and 40% in 2000, respectively. Between 1995 and 2000, condom use at last sex with
      a non-regular partner increased from 35% to 59% and 20% to 39% among men and
      women, respectively. CONCLUSION: The ecological correlation between the trends in
      HIV prevalence and incidence and the increase in protective sexual behaviour
      during the 1990s makes a compelling case for continuing prevention efforts in
      Uganda.

PMID- 16581759
TI  - HIV prevalence and trends from data in Zimbabwe, 1997-2004.
AB  - BACKGROUND: This paper brings together data from a variety of reports to provide
      a basis for assessing future steps for responding to and monitoring the HIV
      epidemic in Zimbabwe. METHOD: Data reported from four antenatal clinic (ANC)
      surveys conducted between 2000 and 2004, two small local studies in Zimbabwe
      conducted from 1997 through 2003, four general population surveys from 1999
      through 2003, and service statistics covering 1990 through 2004 were used to
      describe recent trends in HIV prevalence and incidence, behaviour change, and
      programme provision. RESULTS: HIV prevalence among pregnant women attending ANCs
      declined substantially from 32.1% in 2000 to 23.9% in 2004. The local studies
      confirmed the decline in prevalence. However, prevalence continued to be high.
      Sexual behaviour data from surveys suggests a reduction in sexual experience
      before age 15 years among both males and females age 15-19 years, and in the
      proportions of males and females aged 15-29 years reporting non-regular sexual
      partners in the past 12 months. Reported condom use with non-regular partners has
      been high since 1999. Condom distribution and HIV counseling and testing
      increased from 2000 to 2004. DISCUSSION: On the basis of examination of data from
      a variety of sources, the recent decrease in HIV prevalence may be related to
      recent reductions in early-age sexual activity and non-regular sexual
      partnerships and increases in condom use. Comparison of data from sentinel
      surveillance systems, population based serosurveys, local studies, and service
      statistics provide increased confidence that a decline in HIV prevalence in
      Zimbabwe is actually happening in the population.

PMID- 16581760
TI  - Criteria for detecting and understanding changes in the risk of HIV infection at
      a national level in generalised epidemics.
AB  - Identification of causes of changes in prevalence and incidence of HIV at a
      national level is important for planning future prevention and intervention
      needs. However, the slow progression to disease and the sensitive and
      stigmatising nature of the associated behaviours can make this difficult.
      Changing rates of incidence are to be expected as an epidemic progresses, but
      separating background changes from those brought about by changes in behaviour
      and interventions requires careful analysis. This paper discusses the criteria
      required to determine whether observed changes in HIV prevalence are the result
      of changes in behaviour.

PMID- 16581761
TI  - Measuring trends in prevalence and incidence of HIV infection in countries with
      generalised epidemics.
AB  - OBJECTIVE: Review of recent data and practice to derive guidance on questions
      relating to the measurement and analysis of trends in HIV prevalence and
      incidence. RESULTS: HIV prevalence among pregnant women attending antenatal
      clinics (ANCs) remains the principal data source to inform trends in the
      epidemic. Other data sources are: less available, representative of a small
      section of the population (sex workers, occupational groups), subject to
      additional bias (for example, voluntary counselling and testing service
      statistics), or are not yet available for multiple years (national surveys).
      Validity of HIV prevalence results may change over time due to improvements in
      HIV tests per se and implementation of laboratory quality assurance systems. The
      newer laboratory tests for recent infections require further validation and
      development of methodology to derive estimates of HIV incidence. CONCLUSIONS:
      Issues to consider during statistical analyses of trends among ANC attendees are:
      inclusion of consistent sites only, use of confidence intervals, stratification
      by site when performing a statistical test for trend, the need for at least three
      observations in a surveillance system with data collection every one to two
      years, and sound judgement. Trends in HIV prevalence among pregnant 15-24 year
      olds attending ANCs can be used to approximate trends in incidence. Indepth small
      area research studies are useful to inform the interpretation of surveillance
      data and provide directly measured trends in prevalence and incidence. Modelling
      can assess changes over time in prevalence, incidence, and mortality at the same
      time. Modelling tools need to be further developed to allow incorporation of
      estimates of HIV incidence and mortality, as these data are likely to become
      available in the future. To increase their explanatory power, models should also
      be extended to incorporate programmatic inputs.

PMID- 16581762
TI  - Behavioural data as an adjunct to HIV surveillance data.
AB  - BACKGROUND: Second generation surveillance for HIV aims to improve the validity
      and utility of routine serial HIV prevalence data. It includes the collection of
      data on sexual behaviour and sexually transmitted disease prevalence. METHODS:
      This paper reviews the function of sexual behaviour data in HIV surveillance and
      the methods used to determine which behaviours are monitored and how changes in
      behaviour can be assessed. RESULTS: Sexual behaviour data provide a poor
      predictor of the future spread of HIV, but these data can provide corroboration
      of changes in HIV incidence and assist in attributing changes to particular
      aspects of risk. Significance tests should be used to assess changes in
      behaviour, but this requires transparent reporting of methods and sample sizes.
      CONCLUSIONS: Collection of behavioural data will provide important retrospective
      information about the HIV epidemic progress and should not be neglected because
      of the focus on improving HIV sero-surveillance.

PMID- 16581763
TI  - Assessment of trends in biological and behavioural surveillance data: is there
      any evidence of declining HIV prevalence or incidence in Malawi?
AB  - OBJECTIVES: In 2003 an estimated 87 000 AIDS deaths and approximately 110 000 new
      infections occurred in Malawi. This paper aimed to analyse and review HIV
      prevalence trends in conjunction with other second generation surveillance data
      including behavioural data and, therefore, to describe trends in HIV prevalence
      and behaviours related to HIV transmission. METHODS: In order to determine the
      extent of the problem, HIV prevalence in Malawi has been monitored through
      testing women attending antenatal clinics in 19 sentinel sites consistently since
      1994. These sites are classified as urban, semi-urban, and rural. RESULTS: The
      overall HIV prevalence for all 19 ANC sentinel sites in 2003 was 19.8% (95% CI
      19.0% to 20.7%). The central region urban/semi-urban sites showed a decline in
      prevalence from 1999 to 2003. Since 1997, overall national incidence estimates
      remained stable. This stable incidence estimate is supported by the proxy of
      fairly stable prevalence in ANC attendees aged 15-24 years. HIV sentinel
      surveillance data for Lilongwe city showed a significant linear decline in
      prevalence (p<0.00001) over the last seven years for both all ANC attendees and
      those aged 15-24 years suggesting that incidence has declined over the time
      period. CONCLUSION: The available epidemiological and behavioural surveillance
      data show that HIV prevalence has declined in several urban and semi-urban areas,
      specifically in the central region with Lilongwe (capital of Malawi) showing
      exceptionally strong evidence of decline. In some rural areas, particularly in
      the northern region there is some evidence of an increasing trend in HIV
      prevalence.

PMID- 16581764
TI  - Multiple functions of the integrin alpha6beta4 in epidermal homeostasis and
      tumorigenesis.

PMID- 16581765
TI  - Keap1 recruits Neh2 through binding to ETGE and DLG motifs: characterization of
      the two-site molecular recognition model.
AB  - The expression of the phase 2 detoxification enzymes and antioxidant proteins is
      induced at the transcriptional level by Nrf2 and negatively regulated at the
      posttranslational level by Keap1 through protein-protein interactions with and
      subsequent proteolysis of Nrf2. We found that the Neh2 domain of Nrf2 is an
      intrinsically disordered but biologically active regulatory domain containing a
      33-residue central alpha-helix followed by a mini antiparallel beta-sheet.
      Isothermal calorimetry analysis indicated that one Neh2 molecule interacts with
      two molecules of Keap1 via two binding sites, the stronger binding ETGE motif and
      the weaker binding DLG motif. Nuclear magnetic resonance titration study showed
      that these two motifs of the Neh2 domain bind to an overlapping site on the
      bottom surface of the beta-propeller structure of Keap1. In contrast, the central
      alpha-helix of the Neh2 domain does not have any observable affinity to Keap1,
      suggesting that this region may serve as a bridge connecting the two motifs for
      the association with the two beta-propeller structures of a dimer of Keap1. Based
      on these observations, we propose that Keap1 recruits Nrf2 by the ETGE motif and
      that the DLG motif of the Neh2 domain locks its lysine-rich central alpha-helix
      in a correct position to benefit ubiquitin signaling.

PMID- 16581766
TI  - Permissive effects of oxygen on cyclic AMP and interleukin-1 stimulation of
      surfactant protein A gene expression are mediated by epigenetic mechanisms.
AB  - Surfactant protein A (SP-A) is important for immune defense within the alveolus.
      Cyclic AMP (cAMP) stimulation of SP-A expression in lung type II cells is O(2)
      dependent and mediated by increased phosphorylation and binding of thyroid
      transcription factor 1 (TTF-1) to an upstream response element (TTF-1-binding
      element [TBE]). Interleukin-1 (IL-1) stimulation of SP-A expression is mediated
      by NF-kappaB (p65/p50) activation and increased binding to the TBE. In this
      study, we found that O(2) also was permissive for IL-1 induction of SP-A
      expression and for cAMP and IL-1 stimulation of type II cell nuclear protein
      binding to the TBE. Using chromatin immunoprecipitation, we observed that when
      type II cells were cultured in 20% O(2), cAMP and IL-1 stimulated the recruitment
      of TTF-1, p65, CBP, and steroid receptor coactivator 1 to the TBE region of the
      SP-A promoter and increased local acetylation of histone H3; these effects were
      prevented by hypoxia. Hypoxia markedly reduced global levels of CBP and
      acetylated histone H3 and increased the expression of histone deacetylases.
      Furthermore, hypoxia caused a global increase in histone H3 dimethylated on Lys9
      and increased the association of dimethyl histone H3 with the SP-A promoter.
      These results, together with findings that the histone deacetylase inhibitor
      trichostatin A and the methyltransferase inhibitor 5'-deoxy(5'
      methylthio)adenosine markedly enhanced SP-A expression in lung type II cells,
      suggest that increased O(2) availability to type II cells late in gestation
      causes epigenetic changes that permit access of TTF-1 and NF-kappaB to the SP-A
      promoter. The binding of these transcription factors facilitates the recruitment
      of coactivators, resulting in the further opening of the chromatin structure and
      activation of SP-A transcription.

PMID- 16581767
TI  - Mnd1/Hop2 facilitates Dmc1-dependent interhomolog crossover formation in meiosis
      of budding yeast.
AB  - During meiosis, each chromosome must pair with its homolog and undergo meiotic
      crossover recombination in order to segregate properly at the first meiotic
      division. Recombination in meiosis in Saccharomyces cerevisiae relies on two
      Escherichia coli recA homologs, Rad51 and Dmc1, as well as the more recently
      discovered heterodimer Mnd1/Hop2. Meiotic recombination in S. cerevisiae mnd1 and
      hop2 single mutants is initiated via double-strand breaks (DSBs) but does not
      progress beyond this stage; heteroduplex DNA, joint molecules, and crossovers are
      not detected. Whereas hop2 and mnd1 single mutants are profoundly recombination
      defective, we show that mnd1 rad51, hop2 rad51, and mnd1 rad17 double mutants are
      able to carry out crossover recombination. Interestingly, noncrossover
      recombination is absent, indicating a role for Mnd1/Hop2 in the designation of
      DSBs for noncrossover recombination. We demonstrate that in the rad51 mnd1 double
      mutant, recombination is more likely to occur between repetitive sequences on
      nonhomologous chromosomes. Our results support a model in which Mnd1/Hop2 is
      required for DNA-DNA interactions that help ensure Dmc1-mediated stable strand
      invasion between homologous chromosomes, thereby preserving genomic integrity.

PMID- 16581768
TI  - Novel role for RbAp48 in tissue-specific, estrogen deficiency-dependent apoptosis
      in the exocrine glands.
AB  - Although tissue-specific apoptosis in the exocrine glands in estrogen-deficient
      mice may contribute to the development of autoimmune exocrinopathy, the molecular
      mechanism responsible for tissue-specific apoptosis remains obscure. Here we show
      that RbAp48 overexpression induces p53-mediated apoptosis in the exocrine glands
      caused by estrogen deficiency. RbAp48-inducible transfectant results in rapid
      apoptosis with p53 phosphorylation (Ser9) and alpha-fodrin cleavage. Reducing the
      expression of RbAp48 through small interfering RNA inhibits the apoptosis.
      Prominent RbAp48 expression with apoptosis was observed in the exocrine glands of
      C57BL/6 ovariectomized (OVX) mice but not in OVX estrogen receptor alpha(-/-),
      p53(-/-), and E2F-1(-/-) mice. Indeed, transgenic expression of the RbAp48 gene
      induced apoptosis in the exocrine glands but not in other organs. These findings
      indicate that estrogen deficiency initiates p53-mediated apoptosis in the
      exocrine gland cells through RbAp48 overexpression and exerts a possible gender
      based risk of autoimmune exocrinopathy in postmenopausal women.

PMID- 16581769
TI  - NF-kappaB regulates spatial memory formation and synaptic plasticity through
      protein kinase A/CREB signaling.
AB  - Synaptic activity-dependent de novo gene transcription is crucial for long
      lasting neuronal plasticity and long-term memory. In a forebrain neuronal
      conditional NF-kappaB-deficient mouse model, we demonstrate here that the
      transcription factor NF-kappaB regulates spatial memory formation, synaptic
      transmission, and plasticity. Gene profiling experiments and analysis of
      regulatory regions identified the alpha catalytic subunit of protein kinase A
      (PKA), an essential memory regulator, as a new NF-kappaB target gene.
      Consequently, NF-kappaB inhibition led to a decrease in forskolin-induced CREB
      phosphorylation. Collectively, these results disclose a novel hierarchical
      transcriptional network involving NF-kappaB, PKA, and CREB that leads to
      concerted nuclear transduction of synaptic signals in neurons, accounting for the
      critical function of NF-kappaB in learning and memory.

PMID- 16581770
TI  - Subcellular targeting of p33ING1b by phosphorylation-dependent 14-3-3 binding
      regulates p21WAF1 expression.
AB  - ING1 is a type II tumor suppressor that affects cell growth, stress signaling,
      apoptosis, and DNA repair by altering chromatin structure and regulating
      transcription. Decreased ING1 expression is seen in several human cancers, and
      mislocalization has been noted in diverse types of cancer cells. Aberrant
      targeting may, therefore, functionally inactivate ING1. Bioinformatics analysis
      identified a sequence between the nuclear localization sequence and plant
      homeodomain domains of ING1 that closely matched the binding motif of 14-3-3
      proteins that target cargo proteins to specific subcellular locales. We find that
      the widely expressed p33(ING1b) splicing isoform of ING1 interacts with members
      of the 14-3-3 family of proteins and that this interaction is regulated by the
      phosphorylation status of ING1. 14-3-3 binding resulted in significant amounts of
      p33(ING1b) protein being tethered in the cytoplasm. As shown previously, ectopic
      expression of p33(ING1b) increased levels of the p21(Waf1) cyclin-dependent
      kinase inhibitor upon UV-induced DNA damage. Overexpression of 14-3-3 inhibited
      the up-regulation of p21(Waf1) by p33(ING1b), consistent with the idea that
      mislocalization blocks at least one of ING1's biological activities. These data
      support the idea that the 14-3-3 proteins play a crucial role in regulating the
      activity of p33(ING1b) by directing its subcellular localization.

PMID- 16581772
TI  - Genome-wide analysis of mRNAs regulated by Drosha and Argonaute proteins in
      Drosophila melanogaster.
AB  - RNA silencing pathways are conserved gene regulation mechanisms that elicit decay
      and/or translational repression of mRNAs complementary to short interfering RNAs
      and microRNAs (miRNAs). The fraction of the transcriptome regulated by these
      pathways is not known, but it is thought that each miRNA may have hundreds of
      targets. To identify transcripts regulated by silencing pathways at the genomic
      level, we examined mRNA expression profiles in Drosophila melanogaster cells
      depleted of four Argonaute paralogs (i.e., AGO1, AGO2, PIWI, or Aubergine) that
      play essential roles in RNA silencing. We also profiled cells depleted of the
      miRNA-processing enzyme Drosha. The results reveal that transcripts
      differentially expressed in Drosha-depleted cells have highly correlated
      expression in the AGO1 knockdown and are significantly enriched in predicted and
      validated miRNA targets. The levels of a subset of miRNA targets are also
      regulated by AGO2. Moreover, AGO1 and AGO2 silence the expression of a common set
      of mobile genetic elements. Together, these results indicate that the functional
      overlap between AGO1 and AGO2 in Drosophila is more important than previously
      thought.

PMID- 16581771
TI  - CCN1/Cyr61 is regulated by the canonical Wnt signal and plays an important role
      in Wnt3A-induced osteoblast differentiation of mesenchymal stem cells.
AB  - Marrow mesenchymal stem cells are pluripotent progenitors that can differentiate
      into bone, cartilage, muscle, and fat cells. Wnt signaling has been implicated in
      regulating osteogenic differentiation of mesenchymal stem cells. Here, we
      analyzed the gene expression profile of mesenchymal stem cells that were
      stimulated with Wnt3A. Among the 220 genes whose expression was significantly
      changed by 2.5-fold, we found that three members of the CCN family, CCN1/Cyr61,
      CCN2/connective tissue growth factor (CTGF), and CCN5/WISP2, were among the most
      significantly up-regulated genes. We further investigated the role of CCN1/Cyr61
      in Wnt3A-regulated osteogenic differentiation. We confirmed that CCN1/Cyr61 was
      up-regulated at the early stage of Wnt3A stimulation. Chromatin
      immunoprecipitation analysis indicates that CCN1/Cyr61 is a direct target of
      canonical Wnt/beta-catenin signaling. RNA interference-mediated knockdown of
      CCN1/Cyr61 expression diminished Wnt3A-induced osteogenic differentiation.
      Furthermore, exogenously expressed CCN1/Cyr61 was shown to effectively promote
      mesenchymal stem cell migration. These findings suggest that tightly regulated
      CCN1/Cyr61 expression may play an important role in Wnt3A-induced osteoblast
      differentiation of mesenchymal stem cells.

PMID- 16581774
TI  - Interaction of the RNP1 motif in PRT1 with HCR1 promotes 40S binding of
      eukaryotic initiation factor 3 in yeast.
AB  - We found that mutating the RNP1 motif in the predicted RRM domain in yeast
      eukaryotic initiation factor 3 (eIF3) subunit b/PRT1 (prt1-rnp1) impairs its
      direct interactions in vitro with both eIF3a/TIF32 and eIF3j/HCR1. The rnp1
      mutation in PRT1 confers temperature-sensitive translation initiation in vivo and
      reduces 40S-binding of eIF3 to native preinitiation complexes. Several findings
      indicate that the rnp1 lesion decreases recruitment of eIF3 to the 40S subunit by
      HCR1: (i) rnp1 strongly impairs the association of HCR1 with PRT1 without
      substantially disrupting the eIF3 complex; (ii) rnp1 impairs the 40S binding of
      eIF3 more so than the 40S binding of HCR1; (iii) overexpressing HCR1-R215I
      decreases the Ts(-) phenotype and increases 40S-bound eIF3 in rnp1 cells; (iv)
      the rnp1 Ts(-) phenotype is exacerbated by tif32-Delta6, which eliminates a
      binding determinant for HCR1 in TIF32; and (v) hcr1Delta impairs 40S binding of
      eIF3 in otherwise wild-type cells. Interestingly, rnp1 also reduces the levels of
      40S-bound eIF5 and eIF1 and increases leaky scanning at the GCN4 uORF1. Thus, the
      PRT1 RNP1 motif coordinates the functions of HCR1 and TIF32 in 40S binding of
      eIF3 and is needed for optimal preinitiation complex assembly and AUG recognition
      in vivo.

PMID- 16581773
TI  - Suppression of intestinal neoplasia by deletion of Dnmt3b.
AB  - Aberrant gene silencing accompanied by DNA methylation is associated with
      neoplastic progression in many tumors that also show global loss of DNA
      methylation. Using conditional inactivation of de novo methyltransferase Dnmt3b
      in Apc(Min/+) mice, we demonstrate that the loss of Dnmt3b has no impact on
      microadenoma formation, which is considered the earliest stage of intestinal
      tumor formation. Nevertheless, we observed a significant decrease in the
      formation of macroscopic colonic adenomas. Interestingly, many large adenomas
      showed regions with Dnmt3b inactivation, indicating that Dnmt3b is required for
      initial outgrowth of macroscopic adenomas but is not required for their
      maintenance. These results support a role for Dnmt3b in the transition stage
      between microadenoma formation and macroscopic colonic tumor growth and further
      suggest that Dnmt3b, and by extension de novo methylation, is not required for
      maintaining tumor growth after this transition stage has occurred.

PMID- 16581775
TI  - Proteasome activator PA200 is required for normal spermatogenesis.
AB  - The PA200 proteasome activator is a broadly expressed nuclear protein. Although
      how PA200 normally functions is not fully understood, it has been suggested to be
      involved in the repair of DNA double-strand breaks (DSBs). The PA200 gene (Psme4)
      is composed of 45 coding exons spanning 108 kb on mouse chromosome 11. We
      generated a PA200 null allele (PA200(Delta)) through Cre-loxP-mediated
      interchromosomal recombination after targeting loxP sites at either end of the
      locus. PA200(Delta/Delta) mice are viable and have no obvious developmental
      abnormalities. Both lymphocyte development and immunoglobulin class switching,
      which rely on the generation and repair of DNA DSBs, are unperturbed in
      PA200(Delta/Delta) mice. Additionally, PA200(Delta/Delta) embryonic stem cells do
      not exhibit increased sensitivity to either ionizing radiation or bleomycin.
      Thus, PA200 is not essential for the repair of DNA DSBs generated in these
      settings. Notably, loss of PA200 led to a marked reduction in male, but not
      female, fertility. This was due to defects in spermatogenesis observed in meiotic
      spermatocytes and during the maturation of postmeiotic haploid spermatids. Thus,
      PA200 serves an important nonredundant function during spermatogenesis,
      suggesting that the efficient generation of male gametes has distinct protein
      metabolic requirements.

PMID- 16581776
TI  - NKX3.1 is regulated by protein kinase CK2 in prostate tumor cells.
AB  - Diminished expression of NKX3.1 is associated with prostate cancer progression in
      humans, and in mice, loss of nkx3.1 leads to epithelial cell proliferation and
      altered gene expression patterns. The NKX3.1 amino acid sequence includes
      multiple potential phosphoacceptor sites for protein kinase CK2. To investigate
      posttranslational regulation of NKX3.1, phosphorylation of NKX3.1 by CK2 was
      studied. In vitro kinase assays followed by mass spectrometric analyses
      demonstrated that CK2 phosphorylated recombinant NKX3.1 on Thr89 and Thr93.
      Blocking CK2 activity in LNCaP cells with apigenin or 5,6-dichlorobenzimidazole
      riboside led to a rapid decrease in NKX3.1 accumulation that was rescued by
      proteasome inhibition. Replacing Thr89 and Thr93 with alanines decreased NKX3.1
      stability in vivo. Small interfering RNA knockdown of CK2alpha' but not CK2alpha
      also led to a decrease in NKX3.1 steady-state level. In-gel kinase assays and
      Western blot analyses using fractionated extracts of LNCaP cells demonstrated
      that free CK2alpha' could phosphorylate recombinant human and mouse NKX3.1,
      whereas CK2alpha' liberated from the holoenzyme could not. These data establish
      CK2 as a regulator of NKX3.1 in prostate tumor cells and provide evidence for
      functionally distinct pools of CK2alpha' in LNCaP cells.

PMID- 16581777
TI  - Methylation of histone H3 mediates the association of the NuA3 histone
      acetyltransferase with chromatin.
AB  - The SAS3-dependent NuA3 histone acetyltransferase complex was originally
      identified on the basis of its ability to acetylate histone H3 in vitro. Whether
      NuA3 is capable of acetylating histones in vivo, or how the complex is targeted
      to the nucleosomes that it modifies, was unknown. To address this question, we
      asked whether NuA3 is associated with chromatin in vivo and how this association
      is regulated. With a chromatin pulldown assay, we found that NuA3 interacts with
      the histone H3 amino-terminal tail, and loss of the H3 tail recapitulates
      phenotypes associated with loss of SAS3. Moreover, mutation of histone H3 lysine
      14, the preferred site of acetylation by NuA3 in vitro, phenocopies a unique
      sas3Delta phenotype, suggesting that modification of this residue is important
      for NuA3 function. The interaction of NuA3 with chromatin is dependent on the
      Set1p and Set2p histone methyltransferases, as well as their substrates, histone
      H3 lysines 4 and 36, respectively. These results confirm that NuA3 is functioning
      as a histone acetyltransferase in vivo and that histone H3 methylation provides a
      mark for the recruitment of NuA3 to nucleosomes.

PMID- 16581778
TI  - The BUR1 cyclin-dependent protein kinase is required for the normal pattern of
      histone methylation by SET2.
AB  - BUR1 and BUR2 encode the catalytic and regulatory subunits of a cyclin-dependent
      protein kinase complex that is essential for normal growth and has a general role
      in transcription elongation. To gain insight into its specific role in vivo, we
      identified mutations that reverse the severe growth defect of bur1Delta cells.
      This selection identified mutations in SET2, which encodes a histone methylase
      that targets lysine 36 of histone H3 and, like BUR1, has a poorly characterized
      role during transcription elongation. This genetic relationship indicates that
      SET2 activity is required for the growth defect observed in bur1Delta strains.
      This SET2-dependent growth inhibition occurs via methylation of histone H3 on
      lysine 36, since a methylation-defective allele of SET2 or a histone H3 K36R
      mutation also suppressed bur1Delta. We have explored the relationship between
      BUR1 and SET2 at the biochemical level and find that histone H3 is
      monomethylated, dimethylated, and trimethylated on lysine 36 in wild-type cells,
      but trimethylation is significantly reduced in bur1 and bur2 mutant strains. A
      similar methylation pattern is observed in RNA polymerase II C-terminal domain
      truncation mutants and in an spt16 mutant strain. Chromatin immunoprecipitation
      assays reveal that the transcription-dependent increase in trimethylated K36 over
      open reading frames is significantly reduced in bur2Delta strains. These results
      establish links between a regulatory protein kinase and histone methylation and
      lead to a model in which the Bur1-Bur2 complex counteracts an inhibitory effect
      of Set2-dependent histone methylation.

PMID- 16581779
TI  - Cyclic AMP selectively uncouples mitogen-activated protein kinase cascades from
      activating signals.
AB  - Cells integrate signals to select the appropriate response from an array of
      possible outcomes. Signal integration causes the reorganization of signaling
      pathways by undescribed events. To analyze the molecular changes in signaling
      pathways that elicit different responses, we focused on the interaction between
      cyclic AMP (cAMP) and growth factors. We show that the activation of
      extracellular signal-regulated kinase 5 (ERK5), but not ERK1/2, by growth factors
      is disrupted by cAMP through cAMP-dependent protein kinase (PKA). Activation of
      MEKK2, a mitogen-activated protein (MAP) kinase kinase kinase upstream of ERK5
      that is required for growth factor activation of ERK5, is also disrupted by PKA.
      Transcription of c-Jun is induced by ERK5, and like ERK5, c-Jun induction is also
      blocked by cAMP. Transcription from the serum response element, like activation
      of ERK1/2, is not blocked by cAMP. Collectively, these results support a model in
      which cAMP shapes the growth factor-induced cellular response through PKA
      dependent uncoupling of selected MAP kinase cascades from activating signals.

PMID- 16581780
TI  - Hepatitis C virus nonstructural 5B protein regulates tumor necrosis factor alpha
      signaling through effects on cellular IkappaB kinase.
AB  - Hepatitis C virus (HCV) NS5B protein is a membrane-associated phosphoprotein that
      possesses an RNA-dependent RNA polymerase activity. We recently reported that
      NS5A protein interacts with TRAF2 and modulates tumor necrosis factor alpha (TNF
      alpha)-induced NF-kappaB and Jun N-terminal protein kinase (JNK). Since NS5A and
      NS5B are the essential components of the HCV replication complex, we examined
      whether NS5B could modulate TNF-alpha-induced NF-kappaB and JNK activation. In
      this study, we have demonstrated that TNF-alpha-induced NF-kappaB activation is
      inhibited by NS5B protein in HEK293 and hepatic cells. Furthermore, NS5B protein
      inhibited both TRAF2- and IKK-induced NF-kappaB activation. Using
      coimmunoprecipitation assays, we show that NS5B interacts with IKKalpha. Most
      importantly, NS5B protein in HCV subgenomic replicon cells interacted with
      endogenous IKKalpha, and then TNF-alpha-mediated IKKalpha kinase activation was
      significantly decreased by NS5B. Using in vitro kinase assay, we have further
      found that NS5B protein synergistically activated TNF-alpha-mediated JNK activity
      in HEK293 and hepatic cells. These data suggest that NS5B protein modulates TNF
      alpha signaling pathways and may contribute to HCV pathogenesis.

PMID- 16581781
TI  - GA-binding protein and p300 are essential components of a retinoic acid-induced
      enhanceosome in myeloid cells.
AB  - Expression of CD18, the beta chain of the leukocyte integrins, is
      transcriptionally regulated by retinoic acid (RA) in myeloid cells. Full RA
      responsiveness of the CD18 gene requires its proximal promoter, which lacks a
      retinoic acid response element (RARE). Rather, RA responsiveness of the CD18
      proximal promoter requires ets sites that are bound by GA-binding protein (GABP).
      The transcriptional coactivator, p300, further increases CD18 RA responsiveness.
      We demonstrate that GABPalpha, the ets DNA-binding subunit of GABP, physically
      interacts with p300 in myeloid cells. This interaction involves the GABPalpha
      pointed domain (PNT) and identifies p300 as the first known interaction partner
      of GABPalpha PNT. Expression of the PNT domain, alone, disrupts the GABPalpha
      p300 interaction and decreases the RA responsiveness of the CD18 proximal
      promoter. Chromatin immunoprecipitation and chromosome conformation capture
      demonstrate that, in the presence of RA, GABPalpha and p300 at the proximal
      promoter recruit retinoic acid receptor/retinoid X receptor from a distal RARE to
      form an enhanceosome. A dominant negative p300 construct disrupts enhanceosome
      formation and reduces the RA responsiveness of CD18. Thus, proteins on the CD18
      proximal promoter recruit the distal RARE in the presence of RA. This is the
      first description of an RA-induced enhanceosome and demonstrates that GABP and
      p300 are essential components of CD18 RA responsiveness in myeloid cells.

PMID- 16581782
TI  - Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the
      membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation
      and down-regulation of TRAF2 expression.
AB  - NF-kappaB is critical for determining cellular sensitivity to apoptotic stimuli
      by regulating both mitochondrial and death receptor apoptotic pathways. The
      endoplasmic reticulum (ER) emerges as a new apoptotic signaling initiator.
      However, the mechanism by which ER stress activates NF-kappaB and its role in
      regulation of ER stress-induced cell death are largely unclear. Here, we report
      that, in response to ER stress, IKK forms a complex with IRE1alpha through the
      adapter protein TRAF2. ER stress-induced NF-kappaB activation is impaired in
      IRE1alpha knockdown cells and IRE1alpha(-/-) MEFs. We found, however, that
      inhibiting NF-kappaB significantly decreased ER stress-induced cell death in a
      caspase-8-dependent manner. Gene expression analysis revealed that ER stress
      induced expression of tumor necrosis factor alpha (TNF-alpha) was IRE1alpha and
      NF-kappaB dependent. Blocking TNF receptor 1 signaling significantly inhibited ER
      stress-induced cell death. Further studies suggest that ER stress induces down
      regulation of TRAF2 expression, which impairs TNF-alpha-induced activation of NF
      kappaB and c-Jun N-terminal kinase and turns TNF-alpha from a weak to a powerful
      apoptosis inducer. Thus, ER stress induces two signals, namely TNF-alpha
      induction and TRAF2 down-regulation. They work in concert to amplify ER-initiated
      apoptotic signaling through the membrane death receptor.

PMID- 16581783
TI  - Evidence that poly(A) binding protein C1 binds nuclear pre-mRNA poly(A) tails.
AB  - In mammalian cells, poly(A) binding protein C1 (PABP C1) has well-known roles in
      mRNA translation and decay in the cytoplasm. However, PABPC1 also shuttles in and
      out of the nucleus, and its nuclear function is unknown. Here, we show that
      PABPC1, like the major nuclear poly(A) binding protein PABPN1, associates with
      nuclear pre-mRNAs that are polyadenylated and intron containing. PABPC1 does not
      bind nonpolyadenylated histone mRNA, indicating that the interaction of PABPC1
      with pre-mRNA requires a poly(A) tail. Consistent with this conclusion, UV cross
      linking results obtained using intact cells reveal that PABPC1 binds directly to
      pre-mRNA poly(A) tails in vivo. We also show that PABPC1 immunopurifies with
      poly(A) polymerase, suggesting that PABPC1 is acquired by polyadenylated
      transcripts during poly(A) tail synthesis. Our findings demonstrate that PABPC1
      associates with polyadenylated transcripts earlier in mammalian mRNA biogenesis
      than previously thought and offer insights into the mechanism by which PABPC1 is
      recruited to newly synthesized poly(A). Our results are discussed in the context
      of pre-mRNA processing and stability and mRNA trafficking and the pioneer round
      of translation.

PMID- 16581785
TI  - Positive and negative regulation of the innate antiviral response and beta
      interferon gene expression by deacetylation.
AB  - Beta interferon (IFN-beta) gene expression in response to virus infection relies
      on the dynamic assembly of a multiprotein enhanceosome complex that is initiated
      by the activation of two inducible transcription factors, interferon regulatory
      factor 3 (IRF3) and NF-kappaB. Virus or double-stranded RNA-induced activation of
      IFN-beta gene expression is prevented by the addition of protein deacetylase
      inhibitors. The isolated IRF-responsive positive regulatory domain was found to
      require deacetylation for its activity, but IRF3 protein activation leading to
      its nuclear translocation and DNA binding was not impaired by deacetylase
      inhibition. In contrast, NF-kappaB activity was not affected by deacetylase
      inhibitors. RNA interference indicated that several deacetylase enzymes,
      including histone deacetylase 1 (HDAC1), HDAC8, and HDAC6, influence IFN-beta
      gene expression with opposing effects. While HDAC1 and HDAC8 repress IFN-beta
      expression, HDAC6 acts as a coactivator essential for enhancer activity. Virus
      replication is enhanced in HDAC6-depleted cells, demonstrating HDAC6 is an
      essential component of innate antiviral immunity.

PMID- 16581784
TI  - Transcription of a donor enhances its use during double-strand break-induced gene
      conversion in human cells.
AB  - Homologous recombination (HR) mediates accurate repair of double-strand breaks
      (DSBs) but carries the risk of large-scale genetic change, including loss of
      heterozygosity, deletions, inversions, and translocations. Nearly one-third of
      the human genome consists of repetitive sequences, and DSB repair by HR often
      requires choices among several homologous repair templates, including homologous
      chromosomes, sister chromatids, and linked or unlinked repeats. Donor preference
      during DSB-induced gene conversion was analyzed by using several HR substrates
      with three copies of neo targeted to a human chromosome. Repair of I-SceI
      nuclease-induced DSBs in one neo (the recipient) required a choice between two
      donor neo genes. When both donors were downstream, there was no significant bias
      for proximal or distal donors. When donors flanked the recipient, we observed a
      marked (85%) preference for the downstream donor. Reversing the HR substrate in
      the chromosome eliminated this preference, indicating that donor choice is
      influenced by factors extrinsic to the HR substrate. Prior indirect evidence
      suggested that transcription might increase donor use. We tested this question
      directly and found that increased transcription of a donor enhances its use
      during gene conversion. A preference for transcribed donors would minimize the
      use of nontranscribed (i.e., pseudogene) templates during repair and thus help
      maintain genome stability.

PMID- 16581787
TI  - CtIP activates its own and cyclin D1 promoters via the E2F/RB pathway during G1/S
      progression.
AB  - Cell cycle progression from G(1) to S phase is mainly controlled by E2F
      transcription factors and RB family proteins. Previously we showed that the
      presence of CtIP is essential for G(1)/S transition in primary mouse blastocysts,
      as well as in NIH 3T3 cells. However, how CtIP executes this function remains to
      be elucidated. Here we show that in NIH 3T3 cells the expression of CtIP is
      regulated by the E2F/RB pathway during late G(1) and S phases. The presence of
      wild-type CtIP, but not the E157K mutant form, which failed to interact with RB,
      enhanced its own promoter activity. Chromatin immunoprecipitation analysis
      indicated that the recruitment of CtIP to its promoter occurs concomitantly with
      TFIIB, a component of the RNA polymerase II complex, and with dissociation of RB
      from the promoter during late G(1) and G(1)/S transition. Similar positive
      regulation of cyclin D1 expression by CtIP was also observed. Consistently, cells
      expressing the CtIP(E157K) protein alone exhibited growth retardation, an
      increase in the G(1) population, and a decrease in the S-phase population. Taken
      together, these results suggest that, contrary to the postulated universal
      corepressor role, CtIP activates a subset of E2F-responsive promoters by
      releasing RB-imposed repression and therefore promotes G(1)/S progression.

PMID- 16581786
TI  - The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the
      protein-ubiquitin ligase SCFSkp2.
AB  - MEF is an ETS-related transcription factor with strong transcriptional activating
      activity that affects hematopoietic stem cell behavior and is required for normal
      NK cell and NK T-cell development. The MEF (also known as ELF4) gene is repressed
      by several leukemia-associated fusion transcription factor proteins (PML-retinoic
      acid receptor alpha and AML1-ETO), but it is also activated by retroviral
      insertion in several cancer models. We have previously shown that cyclin A
      dependent phosphorylation of MEF largely restricts its activity to the G(1) phase
      of the cell cycle; we now show that MEF is a short-lived protein whose expression
      level also peaks during late G(1) phase. Mutagenesis studies show that the rapid
      turnover of MEF in S phase is dependent on the specific phosphorylation of
      threonine 643 and serine 648 at the C terminus of MEF by cdk2 and on the
      Skp1/Cul1/F-box (SCF) E3 ubiquitin ligase complex SCF(Skp2), which targets MEF
      for ubiquitination and proteolysis. Overexpression of MEF drives cells through
      the G(1)/S transition, thereby promoting cell proliferation. The tight regulation
      of MEF levels during the cell cycle contributes to its effects on regulating cell
      cycle entry and cell proliferation.

PMID- 16581788
TI  - The Spt4p subunit of yeast DSIF stimulates association of the Paf1 complex with
      elongating RNA polymerase II.
AB  - The Paf1 complex (Paf1C) interacts with RNA polymerase II (Pol II) and promotes
      histone methylation of transcribed coding sequences, but the mechanism of Paf1C
      recruitment is unknown. We show that Paf1C is not recruited directly by the
      activator Gcn4p but is dependent on preinitiation complex assembly and Ser5
      carboxy-terminal domain phosphorylation for optimal association with ARG1 coding
      sequences. Importantly, Spt4p is required for Paf1C occupancy at ARG1 (and other
      genes) and for Paf1C association with Ser5-phosphorylated Pol II in cell
      extracts, whereas Spt4p-Pol II association is independent of Paf1C. Since
      spt4Delta does not reduce levels of Pol II at ARG1, Ser5 phosphorylation, or
      Paf1C expression, it appears that Spt4p (or its partner in DSIF, Spt5p) provides
      a platform on Pol II for recruiting Paf1C following Ser5 phosphorylation and
      promoter clearance. spt4Delta reduces trimethylation of Lys4 on histone H3,
      demonstrating a new role for yeast DSIF in promoting a Paf1C-dependent function
      in elongation.

PMID- 16581790
TI  - A leaderless mRNA can bind to mammalian 80S ribosomes and direct polypeptide
      synthesis in the absence of translation initiation factors.
AB  - Translation initiation in eukaryotic cells is known to be a complex multistep
      process which involves numerous protein factors. Here we demonstrate that
      leaderless mRNAs with initiator Met-tRNA can bind directly to 80S mammalian
      ribosomes in the absence of initiation factors and that the complexes thus formed
      are fully competent for the subsequent steps of polypeptide synthesis. We show
      that the canonical 48S pathway of eukaryotic translation initiation has no
      obvious advantage over the 80S pathway of translation initiation on leaderless
      mRNAs and suggest that, in the presence of competing mRNAs containing a leader,
      the latter mechanism will be preferred. The direct binding of the leaderless mRNA
      to the 80S ribosome was precluded when such an mRNA was supplied with a 5'
      leader, irrespective of whether it was in a totally single-stranded conformation
      or was prone to base pairing. The striking similarity between the mechanisms of
      binding of leaderless mRNAs with mammalian 80S or bacterial 70S ribosomes gives
      support to the idea that the alternative mode of translation initiation used by
      leaderless mRNAs represents a relic from early steps in the evolution of the
      translation apparatus.

PMID- 16581789
TI  - Independent recruitment of mediator and SAGA by the activator Met4.
AB  - Mediator is a key RNA polymerase II (Pol II) cofactor in the regulation of
      eukaryotic gene expression. It is believed to function as a coactivator linking
      gene-specific activators to the basal Pol II initiation machinery. In support of
      this model, we provide evidence that Mediator serves in vivo as a coactivator for
      the yeast activator Met4, which controls the gene network responsible for the
      biosynthesis of sulfur-containing amino acids and S-adenosylmethionine. In
      addition, we show that SAGA (Spt-Ada-Gcn5-acetyltransferase) is also recruited to
      Met4 target promoters, where it participates in the recruitment of Pol II by a
      mechanism involving histone acetylation. Interestingly, we find that SAGA is not
      required for Mediator recruitment by Met4 and vice versa. Our results provide a
      novel example of functional interplay between Mediator and coactivators involved
      in histone modification.

PMID- 16581791
TI  - Kap120 functions as a nuclear import receptor for ribosome assembly factor Rpf1
      in yeast.
AB  - The nucleocytoplasmic exchange of macromolecules is mediated by receptors
      specialized in passage through the nuclear pore complex. The majority of these
      receptors belong to the importin beta protein family, which has 14 members in
      Saccharomyces cerevisiae. Nine importins carry various cargos from the cytoplasm
      into the nucleus, whereas four exportins mediate nuclear export. Kap120 is the
      only receptor whose transport cargo has not been found previously. Here, we
      characterize Kap120 as an importin for the ribosome maturation factor Rpf1, which
      was identified in a two-hybrid screen. Kap120 binds directly to Rpf1 in vitro and
      is released by Ran-GTP. At least three parallel import pathways exist for Rpf1,
      since nuclear import is defective in strains with the importins Kap120, Kap114,
      and Nmd5 deleted. Both kap120 and rpf1 mutants accumulate large ribosomal
      subunits in the nucleus. The nuclear accumulation of 60S ribosomal subunits in
      kap120 mutants is abolished upon RPF1 overexpression, indicating that Kap120 does
      not function in the actual ribosomal export step but rather in import of ribosome
      maturation factors.

PMID- 16581792
TI  - Galectin binding to Mgat5-modified N-glycans regulates fibronectin matrix
      remodeling in tumor cells.
AB  - Oncogenic signaling stimulates the dynamic remodeling of actin microfilaments and
      substrate adhesions, essential for cell spreading and motility. Transformation is
      associated with increased expression of beta1,6GlcNAc-branched N-glycans,
      products of Golgi beta1,6-acetylglucosaminyltransferase V (Mgat5) and the favored
      ligand for galectins. Herein we report that fibronectin fibrillogenesis and
      fibronectin-dependent cell spreading are deficient in Mgat5(-/-) mammary
      epithelial tumor cells and inhibited in Mgat5(+/+) cells by blocking Golgi N
      glycan processing with swainsonine or by competitive inhibition of galectin
      binding. At an optimum dosage, exogenous galectin-3 added to Mgat5(+/+) cells
      activates focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K),
      recruits conformationally active alpha5beta1-integrin to fibrillar adhesions, and
      increases F-actin turnover. RGD peptide inhibits PI3K-dependent fibronectin
      matrix remodeling and fibronectin-dependent cell motility, while galectin-3
      stimulates and overrides the inhibitory effects of RGD. Antibodies to the
      galectin-3 N-terminal oligomerization domain stimulate alpha5beta1 activation and
      recruitment to fibrillar adhesions in Mgat5(+/+) cells, an effect that is blocked
      by disrupting galectin-glycan binding. Our results demonstrate that fibronectin
      polymerization and tumor cell motility are regulated by galectin-3 binding to
      branched N-glycan ligands that stimulate focal adhesion remodeling, FAK and PI3K
      activation, local F-actin instability, and alpha5beta1 translocation to fibrillar
      adhesions.

PMID- 16581794
TI  - Thyroid hormone receptor alpha1 directly controls transcription of the beta
      catenin gene in intestinal epithelial cells.
AB  - Thyroid hormones, T3 and T4, are known regulators of intestine development. The
      best characterized example is the remodeling of the gastrointestinal tract during
      amphibian metamorphosis. Thyroid hormones act via nuclear receptors, the TRs,
      which are T3-dependent transcription factors. We previously showed that
      intestinal epithelial cell proliferation is controlled by thyroid hormones and
      the TRalpha gene. To analyze the mechanisms responsible, we studied the
      expression of genes belonging to and/or activated by the Wnt/beta-catenin
      pathway, a major actor in the control of physiological and pathological
      epithelial proliferation in the intestine. We show that T3-TRalpha1 controls the
      transcription of the beta-catenin gene in an epithelial cell-autonomous way. This
      is parallel to positive regulation of proliferation-controlling genes such as
      type D cyclins and c-myc, known targets of the Wnt/beta-catenin. In addition, we
      show that the regulation of the beta-catenin gene is direct, as TR binds in vitro
      and in chromatin in vivo to a specific thyroid hormone-responsive element present
      in intron 1 of this gene. This is the first report concerning in vivo
      transcriptional control of the beta-catenin gene. As Wnt/beta-catenin plays a
      crucial role in intestinal tumorigenesis, our observations open a new perspective
      on the study of TRs as potential tumor inducers.

PMID- 16581793
TI  - Transcription elongation factor S-II is required for definitive hematopoiesis.
AB  - Transcription elongation factor S-II/TFIIS promotes readthrough of
      transcriptional blocks by stimulating nascent RNA cleavage activity of RNA
      polymerase II in vitro. The biologic significance of S-II function in higher
      eukaryotes, however, remains unclear. To determine its role in mammalian
      development, we generated S-II-deficient mice through targeted gene disruption.
      Homozygous null mutants died at midgestation with marked pallor, suggesting
      severe anemia. S-II(-/-) embryos had a decreased number of definitive
      erythrocytes in the peripheral blood and disturbed erythroblast differentiation
      in fetal liver. There was a dramatic increase in apoptotic cells in S-II(-/-)
      fetal liver, which was consistent with a reduction in Bcl-x(L) gene expression.
      The presence of phenotypically defined hematopoietic stem cells and in vitro
      colony-forming hematopoietic progenitors in S-II(-/-) fetal liver indicates that
      S-II is dispensable for the generation and differentiation of hematopoietic stem
      cells. S-II-deficient fetal liver cells, however, exhibited a loss of long-term
      repopulating potential when transplanted into lethally irradiated adult mice,
      indicating that S-II deficiency causes an intrinsic defect in the self-renewal of
      hematopoietic stem cells. Thus, S-II has critical and nonredundant roles in
      definitive hematopoiesis.

PMID- 16581795
TI  - Nucleocytoplasmic shuttling of Pak5 regulates its antiapoptotic properties.
AB  - p21-activated kinase 5 (Pak5) is an effector for the small GTPase Cdc42, known to
      activate cell survival signaling pathways. Previously, we have shown that Pak5
      localizes primarily to mitochondria. To study the relationship between Pak5
      localization and its effects on apoptosis, we identified three N-terminal regions
      that regulate the localization of this kinase: a mitochondrial targeting
      sequence, a nuclear export sequence, and a nuclear localization sequence. When
      the first two sequences are deleted, Pak5 is retained in the nucleus and no
      longer protects cells from apoptosis. Moreover, blockade of nuclear export with
      leptomycin B causes endogenous Pak5 to accumulate in the nucleus. Additionally,
      the removal of the N-terminal nuclear localization sequence abolishes Pak5
      translocation to the nucleus. Finally, we show that reduction of endogenous Pak5
      expression in neuroblastoma and neural stem cells increases their sensitivity to
      apoptosis and that this effect is reversed upon reexpression of wild-type Pak5
      but not of a mutant form of Pak5 that cannot localize to mitochondria. These
      results show that Pak5 shuttles from mitochondria to the nucleus and that the
      mitochondrial localization of Pak5 is vital to its effects on cell survival.

PMID- 16581796
TI  - Clathrin adaptor AP2 regulates thrombin receptor constitutive internalization and
      endothelial cell resensitization.
AB  - Protease-activated receptor 1 (PAR1), a G protein-coupled receptor for the
      coagulant protease thrombin, is irreversibly activated by proteolysis.
      Unactivated PAR1 cycles constitutively between the plasma membrane and
      intracellular stores, thereby providing a protected receptor pool that
      replenishes the cell surface after thrombin exposure and leads to rapid
      resensitization to thrombin signaling independent of de novo receptor synthesis.
      Here, we show that AP2, a clathrin adaptor, binds directly to a tyrosine-based
      motif in the cytoplasmic tail of PAR1 and is essential for constitutive receptor
      internalization and cellular recovery of thrombin signaling. Expression of a PAR1
      tyrosine mutant or depletion of AP2 by RNA interference leads to significant
      inhibition of PAR1 constitutive internalization, loss of intracellular uncleaved
      PAR1, and failure of endothelial cells and other cell types to regain thrombin
      responsiveness. Our findings establish a novel role for AP2 in direct regulation
      of PAR1 trafficking, a process critically important to the temporal and spatial
      aspects of thrombin signaling.

PMID- 16581797
TI  - Plasma membrane localization of Ras requires class C Vps proteins and functional
      mitochondria in Saccharomyces cerevisiae.
AB  - Ras proteins are synthesized as cytosolic precursors, but then undergo
      posttranslational lipid addition, membrane association, and subcellular targeting
      to the plasma membrane. Although the enzymes responsible for farnesyl and
      palmitoyl lipid addition have been described, the mechanism by which these
      modifications contribute to the subcellular localization of Ras is not known.
      Following addition of the farnesyl group, Ras associates with the endoplasmic
      reticulum (ER), where palmitoylation occurs in Saccharomyces cerevisiae. The
      subsequent translocation of Ras from the ER to the plasma membrane does not
      require the classical secretory pathway or a functional Golgi apparatus.
      Vesicular and nonvesicular transport pathways for Ras proteins have been
      proposed, but the pathway is not known. Here we describe a genetic screen
      designed to identify mutants defective in Ras trafficking in S. cerevisiae. The
      screen implicates, for the first time, the class C VPS complex in Ras
      trafficking. Vps proteins are best characterized for their role in endosome and
      vacuole membrane fusion. However, the role of the class C Vps complex in Ras
      trafficking is distinct from its role in endosome and vacuole vesicle fusion, as
      a mitochondrial involvement was uncovered. Disruption of class C VPS genes
      results in mitochondrial defects and an accumulation of Ras proteins on
      mitochondrial membranes. Ras also fractionates with mitochondria in wild-type
      cells, where it is detected on the outer mitochondrial membrane by virtue of its
      sensitivity to protease treatment. These results point to a previously
      uncharacterized role of mitochondria in the subcellular trafficking of Ras
      proteins.

PMID- 16581798
TI  - Structure and function of the Saccharomyces cerevisiae Sir3 BAH domain.
AB  - Previous work has shown that the N terminus of the Saccharomyces cerevisiae Sir3
      protein is crucial for the function of Sir3 in transcriptional silencing. Here,
      we show that overexpression of N-terminal fragments of Sir3 in strains lacking
      the full-length protein can lead to some silencing of HML and HMR. Sir3 contains
      a BAH (bromo-adjacent homology) domain at its N terminus. Overexpression of this
      domain alone can lead to silencing as long as Sir1 is overexpressed and Sir2 and
      Sir4 are present. Overexpression of the closely related Orc1 BAH domain can also
      silence in the absence of any Sir3 protein. A previously characterized
      hypermorphic sir3 mutation, D205N, greatly improves silencing by the Sir3 BAH
      domain and allows it to bind to DNA and oligonucleosomes in vitro. A previously
      uncharacterized region in the Sir1 N terminus is required for silencing by both
      the Sir3 and Orc1 BAH domains. The structure of the Sir3 BAH domain has been
      determined. In the crystal, the molecule multimerizes in the form of a left
      handed superhelix. This superhelix may be relevant to the function of the BAH
      domain of Sir3 in silencing.

PMID- 16581799
TI  - Differentiation of trophoblast giant cells and their metabolic functions are
      dependent on peroxisome proliferator-activated receptor beta/delta.
AB  - Mutation of the nuclear receptor peroxisome proliferator-activated receptor
      beta/delta (PPARbeta/delta) severely affects placenta development, leading to
      embryonic death at embryonic day 9.5 (E9.5) to E10.5 of most, but not all,
      PPARbeta/delta-null mutant embryos. While very little is known at present about
      the pathway governed by PPARbeta/delta in the developing placenta, this paper
      demonstrates that the main alteration of the placenta of PPARbeta/delta-null
      embryos is found in the giant cell layer. PPARbeta/delta activity is in fact
      essential for the differentiation of the Rcho-1 cells in giant cells, as shown by
      the severe inhibition of differentiation once PPARbeta/delta is silenced.
      Conversely, exposure of Rcho-1 cells to a PPARbeta/delta agonist triggers a
      massive differentiation via increased expression of 3-phosphoinositide-dependent
      kinase 1 and integrin-linked kinase and subsequent phosphorylation of Akt. The
      links between PPARbeta/delta activity in giant cells and its role on Akt activity
      are further strengthened by the remarkable pattern of phospho-Akt expression in
      vivo at E9.5, specifically in the nucleus of the giant cells. In addition to this
      phosphatidylinositol 3-kinase/Akt main pathway, PPARbeta/delta also induced giant
      cell differentiation via increased expression of I-mfa, an inhibitor of Mash-2
      activity. Finally, giant cell differentiation at E9.5 is accompanied by a
      PPARbeta/delta-dependent accumulation of lipid droplets and an increased
      expression of the adipose differentiation-related protein (also called
      adipophilin), which may participate to lipid metabolism and/or steroidogenesis.
      Altogether, this important role of PPARbeta/delta in placenta development and
      giant cell differentiation should be considered when contemplating the potency of
      PPARbeta/delta agonist as therapeutic agents of broad application.

PMID- 16581800
TI  - Association and regulation of heat shock transcription factor 4b with both
      extracellular signal-regulated kinase mitogen-activated protein kinase and dual
      specificity tyrosine phosphatase DUSP26.
AB  - The heat shock transcription factors (Hsfs) activate the stress-inducible
      expression of heat shock proteins (Hsps) and other molecular chaperones in
      response to stress and, therefore, play an essential role in protein
      disaggregation and protein folding. In humans, missense mutation in the hsf4 gene
      causes cataract, and mice bearing a targeted disruption of the hsf4 gene exhibit
      defects in lens fiber cell differentiation and early cataract formation. Here, we
      show that Hsf4b is a direct target of the mitogen-activated protein (MAP) kinase
      extracellular signal-related kinase (ERK) and that phosphorylation of Hsf4b by
      ERK leads to increased ability of Hsf4b to bind DNA. Surprisingly, Hsf4b also
      interacts with an ERK-specific dual-specificity tyrosine phosphatase named DUSP26
      identified from a yeast two-hybrid screen. While activated ERK phosphorylates
      Hsf4b, DUSP26 controls the activity of ERK, leading to
      phosphorylation/dephosphorylation of Hsf4b, altering its ability to bind DNA.
      Therefore, DUSP26 interaction with Hsf4b places this transcription factor within
      a regulatory circuit in the MAP kinase signaling pathway.

PMID- 16581801
TI  - Translational control of cytochrome c by RNA-binding proteins TIA-1 and HuR.
AB  - Stresses affecting the endoplasmic reticulum (ER) globally modulate gene
      expression patterns by altering posttranscriptional processes such as
      translation. Here, we use tunicamycin (Tn) to investigate ER stress-triggered
      changes in the translation of cytochrome c, a pivotal regulator of apoptosis. We
      identified two RNA-binding proteins that associate with its approximately 900-bp
      long, adenine- and uridine-rich 3' untranslated region (UTR): HuR, which
      displayed affinity for several regions of the cytochrome c 3'UTR, and T-cell
      restricted intracellular antigen 1 (TIA-1), which preferentially bound the
      segment proximal to the coding region. HuR did not appear to influence the
      cytochrome c mRNA levels but instead promoted cytochrome c translation, as HuR
      silencing greatly diminished the levels of nascent cytochrome c protein. By
      contrast, TIA-1 functioned as a translational repressor of cytochrome c, with
      interventions to silence TIA-1 dramatically increasing cytochrome c translation.
      Following treatment with Tn, HuR binding to cytochrome c mRNA decreased, and both
      the presence of cytochrome c mRNA within actively translating polysomes and the
      rate of cytochrome c translation declined. Taken together, our data suggest that
      the translation rate of cytochrome c is determined by the opposing influences of
      HuR and TIA-1 upon the cytochrome c mRNA. Under unstressed conditions, cytochrome
      c mRNA is actively translated, but in response to ER stress agents, both HuR and
      TIA-1 contribute to lowering its biosynthesis rate. We propose that HuR and TIA-1
      function coordinately to maintain precise levels of cytochrome c production under
      unstimulated conditions and to modify cytochrome c translation when damaged cells
      are faced with molecular decisions to follow a prosurvival or a prodeath path.

PMID- 16581802
TI  - An autoregulatory loop directs the tissue-specific expression of p63 through a
      long-range evolutionarily conserved enhancer.
AB  - p63, a p53 family member, is essential for the development of various stratified
      epithelia and is one of the earliest markers of many ectodermal structures,
      including the epidermis, oral mucosa, apical ectodermal ridge, and mammary gland.
      Genetic regulatory mechanisms controlling p63 spatial expression during
      development have not yet been defined. Using a genomic approach, we identified an
      evolutionarily conserved cis-regulatory element, located 160 kb downstream of the
      first p63 exon, which functions as a keratinocyte-specific enhancer and is
      sufficient to recapitulate expression of the endogenous gene during mouse
      embryogenesis. Dissection of the p63 enhancer activity revealed a positive
      autoregulatory loop in which the p63 proteins directly bind to and are essential
      regulators of the enhancer. Accordingly, transactivating p63 isoforms induce
      endogenous p63 expression in cells that do not normally express this gene,
      whereas dominant negative isoforms suppress p63 expression in keratinocytes. In
      addition the transcription factor AP-2 also binds to the enhancer and cooperates
      with p63 to induce its activity. These results demonstrate that a long-range
      autoregulatory loop is involved in the regulation of p63 expression during
      embryonic development and in adult cells.

PMID- 16581803
TI  - Chk1 requirement for high global rates of replication fork progression during
      normal vertebrate S phase.
AB  - Chk1 protein kinase maintains replication fork stability in metazoan cells in
      response to DNA damage and DNA replication inhibitors. Here, we have employed DNA
      fiber labeling to quantify, for the first time, the extent to which Chk1
      maintains global replication fork rates during normal vertebrate S phase. We
      report that replication fork rates in Chk1(-/-) chicken DT40 cells are on average
      half of those observed with wild-type cells. Similar results were observed if
      Chk1 was inhibited or depleted in wild-type DT40 cells or HeLa cells by
      incubation with Chk1 inhibitor or small interfering RNA. In addition, reduced
      rates of fork extension were observed with permeabilized Chk1(-/-) cells in
      vitro. The requirement for Chk1 for high fork rates during normal S phase was not
      to suppress promiscuous homologous recombination at replication forks, because
      inhibition of Chk1 similarly slowed fork progression in XRCC3(-/-) DT40 cells.
      Rather, we observed an increased number of replication fibers in Chk1(-/-) cells
      in which the nascent strand is single-stranded, supporting the idea that slow
      global fork rates in unperturbed Chk1(-/-) cells are associated with the
      accumulation of aberrant replication fork structures.

PMID- 16581804
TI  - Replication fork progression is impaired by transcription in hyperrecombinant
      yeast cells lacking a functional THO complex.
AB  - THO/TREX is a conserved, eukaryotic protein complex operating at the interface
      between transcription and messenger ribonucleoprotein (mRNP) metabolism. THO
      mutations impair transcription and lead to increased transcription-associated
      recombination (TAR). These phenotypes are dependent on the nascent mRNA; however,
      the molecular mechanism by which impaired mRNP biogenesis triggers recombination
      in THO/TREX mutants is unknown. In this study, we provide evidence that deficient
      mRNP biogenesis causes slowdown or pausing of the replication fork in hpr1Delta
      mutants. Impaired replication appears to depend on sequence-specific features
      since it was observed upon activation of lacZ but not leu2 transcription.
      Replication fork progression could be partially restored by hammerhead ribozyme
      guided self-cleavage of the nascent mRNA. Additionally, hpr1Delta increased the
      number of S-phase but not G(2)-dependent TAR events as well as the number of
      budded cells containing Rad52 repair foci. Our results link transcription
      dependent genomic instability in THO mutants with impaired replication fork
      progression, suggesting a molecular basis for a connection between inefficient
      mRNP biogenesis and genetic instability.

PMID- 16581805
TI  - Structural basis for altering the stability of homologous RNAs from a mesophilic
      and a thermophilic bacterium.
AB  - Tertiary RNA structures from thermophilic bacteria generally are more stable than
      their mesophilic homologs. To understand the structural basis of the increase in
      stability, we investigated equilibrium folding of the specificity domain (S
      domain) of RNase P RNA from a mesophilic (Escherichia coli) and a thermophilic
      (Thermus thermophilus) bacterium. Equilibrium folding of both S-domains is
      described by a minimal, three-state folding scheme, U-to-I-to-N. In the I-to-N
      transition of the thermophilic S-domain, more structure forms and protections are
      stronger against T1 nuclease and hydroxyl radical reactions. Phylogenetic
      comparison in the context of the native structure reveals that among 39
      nucleotide differences between these S-domains, 12 likely contribute to higher
      stability. These residues participate in extensive networks of hydrogen bonding,
      stacking, and metal ion coordination throughout the molecule. The thermophilic S
      domain achieves higher stability by mutating strategic base pairs to G-C,
      decreasing surface accessibility of the native state, and increasing the amount
      of structure formation in the native folding transition. An E. coli S-domain
      mutant containing these 12 nt has the same stability and folding cooperativity as
      the T. thermophilus S-domain. E. coli S-domain mutants containing a subset of 4
      or 6 nt have the same stability as the T. thermophilus S-domain but the same
      folding cooperativity as the E. coli S-domain. These results show that increasing
      stability can be accomplished by mutations within a local structure, but
      increasing folding cooperativity needs concerted changes among multiple
      structural units.

PMID- 16581806
TI  - Recognition of RNA by the p53 tumor suppressor protein in the yeast three-hybrid
      system.
AB  - The p53 tumor suppressor protein is a homotetrameric transcription factor whose
      gene is mutated in nearly half of all human cancers. In an unrelated screen of
      RNA/protein interactions using the yeast three-hybrid system, we inadvertently
      detected p53 interactions with several different RNAs. A literature review
      revealed previous reports of both sequence-specific and -non-specific
      interactions between p53 and RNA. Using yeast three-hybrid selections to identify
      preferred RNA partners for p53, we failed to identify primary RNA sequences or
      obvious secondary structures required for p53 binding. The cationic p53 C
      terminus was shown to be required for RNA binding in yeast. We show that while
      p53 strongly discriminates between certain RNAs in the yeast three-hybrid assay,
      the same RNAs are bound equally by p53 in vitro. We further show that the p53 RNA
      binding preferences in yeast are mirrored almost exactly by a recombinant
      tetrameric form of the HIV-1 nucleocapsid (NC) protein thought to be a sequence
      nonspecific RNA-binding protein. However, the possibility of specific RNA binding
      by p53 could not be ruled out because p53 and HIV-1 NC displayed certain
      differences in RNA-binding preference. We conclude that (1) p53 binds RNA in
      vivo, (2) RNA binding by p53 is largely sequence-nonspecific in the yeast
      nucleus, (3) some structure-specific RNA binding by p53 cannot be ruled out, and
      (4) caution is required when interpreting results of RNA screens in the yeast
      three-hybrid system because sequence-dependent differences in RNA folding and
      display can masquerade as sequence-dependent differences in protein recognition.

PMID- 16581808
TI  - Transcriptional termination sequences in the mouse serum albumin gene.
AB  - Poly(A) signals are required for efficient 3' end formation and transcriptional
      termination of most protein-encoding genes transcribed by RNA polymerase II.
      However, transcription can extend far beyond the poly(A) site before termination
      occurs. This implies the existence of further downstream termination signals. In
      mammals, a variety of sequence elements, in addition to the poly(A) site, have
      been implicated in the termination process. For example, termination of the human
      beta- and epsilon-globin genes is mediated by a sequence downstream of the
      poly(A) site that promotes an RNA cotranscriptional cleavage (CoTC). Here we
      report the identification of multiple termination sequences in the mouse serum
      albumin (MSA) 3' flanking region. Many transcripts from this region are cleaved
      cotranscriptionally, implying that such cleavage of pre-mRNA may be a more
      general feature of transcriptional termination.

PMID- 16581807
TI  - The La protein functions redundantly with tRNA modification enzymes to ensure
      tRNA structural stability.
AB  - Although the La protein stabilizes nascent pre-tRNAs from nucleases, influences
      the pathway of pre-tRNA maturation, and assists correct folding of certain pre
      tRNAs, it is dispensable for growth in both budding and fission yeast. Here we
      show that the Saccharomyces cerevisiae La shares functional redundancy with both
      tRNA modification enzymes and other proteins that contact tRNAs during their
      biogenesis. La is important for growth in the presence of mutations in either the
      arginyl tRNA synthetase or the tRNA modification enzyme Trm1p. In addition, two
      pseudouridine synthases, PUS3 and PUS4, are important for growth in strains
      carrying a mutation in tRNA(Arg)(CCG) and are essential when La is deleted in
      these strains. Depletion of Pus3p results in accumulation of the aminoacylated
      mutant tRNA(Arg)(CCG) in nuclei, while depletion of Pus4p results in decreased
      stability of the mutant tRNA. Interestingly, the degradation of mutant unstable
      forms of tRNA(Arg)(CCG) does not require the Trf4p poly(A) polymerase, suggesting
      that yeast cells possess multiple pathways for tRNA decay. These data demonstrate
      that La functions redundantly with both tRNA modifications and proteins that
      associate with tRNAs to achieve tRNA structural stability and efficient
      biogenesis.

PMID- 16581809
TI  - Transmission of mitochondrial DNA following assisted reproduction and nuclear
      transfer.
AB  - Mitochondria are the organelles responsible for producing the majority of a
      cell's ATP and also play an essential role in gamete maturation and embryo
      development. ATP production within the mitochondria is dependent on proteins
      encoded by both the nuclear and the mitochondrial genomes, therefore co
      ordination between the two genomes is vital for cell survival. To assist with
      this co-ordination, cells normally contain only one type of mitochondrial DNA
      (mtDNA) termed homoplasmy. Occasionally, however, two or more types of mtDNA are
      present termed heteroplasmy. This can result from a combination of mutant and
      wild-type mtDNA molecules or from a combination of wild-type mtDNA variants. As
      heteroplasmy can result in mitochondrial disease, various mechanisms exist in the
      natural fertilization process to ensure the maternal-only transmission of mtDNA
      and the maintenance of homoplasmy in future generations. However, there is now an
      increasing use of invasive oocyte reconstruction protocols, which tend to bypass
      mechanisms for the maintenance of homoplasmy, potentially resulting in the
      transmission of either form of mtDNA heteroplasmy. Indeed, heteroplasmy caused by
      combinations of wild-type variants has been reported following cytoplasmic
      transfer (CT) in the human and following nuclear transfer (NT) in various animal
      species. Other techniques, such as germinal vesicle transfer and pronuclei
      transfer, have been proposed as methods of preventing transmission of
      mitochondrial diseases to future generations. However, resulting embryos and
      offspring may contain mtDNA heteroplasmy, which itself could result in
      mitochondrial disease. It is therefore essential that uniparental transmission of
      mtDNA is ensured before these techniques are used therapeutically.

PMID- 16581810
TI  - Protamines and male infertility.
AB  - Protamines are the major nuclear sperm proteins. The human sperm nucleus contains
      two types of protamine: protamine 1 (P1) encoded by a single-copy gene and the
      family of protamine 2 (P2) proteins (P2, P3 and P4), all also encoded by a single
      gene that is transcribed and translated into a precursor protein. The protamines
      were discovered more than a century ago, but their function is not yet fully
      understood. In fact, different hypotheses have been proposed: condensation of the
      sperm nucleus into a compact hydrodynamic shape, protection of the genetic
      message delivered by the spermatozoa, involvement in the processes maintaining
      the integrity and repair of DNA during or after the nucleohistone-nucleoprotamine
      transition and involvement in the epigenetic imprinting of the spermatozoa.
      Protamines are also one of the most variable proteins found in nature, with data
      supporting a positive Darwinian selection. Changes in the expression of P1 and P2
      protamines have been found to be associated with infertility in man. Mutations in
      the protamine genes have also been found in some infertile patients. Transgenic
      mice defective in the expression of protamines also present several structural
      defects in the sperm nucleus and have variable degrees of infertility. There is
      also evidence that altered levels of protamines may result in an increased
      susceptibility to injury in the spermatozoan DNA causing infertility or poor
      outcomes in assisted reproduction. The present work reviews the articles
      published to date on the relationship between protamines and infertility.

PMID- 16581812
TI  - Agonist trigger in the context of OHSS prevention: primum non nocere.

PMID- 16581814
TI  - Are endogenous LH levels during ovarian stimulation for IVF using GnRH analogues
      associated with the probability of ongoing pregnancy? A systematic review.

PMID- 16581816
TI  - Commentary: dietary advice for reducing cardiovascular risk.

PMID- 16581815
TI  - Use of intravenous cyclophosphamide in the prevention of corneal melt: justified
      or not?

PMID- 16581818
TI  - The impact of cardiovascular risk factors on the age-related excess risk of
      coronary heart disease.
AB  - PURPOSE: Differences in cardiovascular risk factor levels have been suggested to
      contribute to the age-related excess risk of coronary heart disease (CHD). The
      aim of this study was to reliably quantify these contributions using a large
      prospective dataset. METHODS: We carried out an individual participant data meta
      analysis of 41 cohort studies (n = 582,134) from Asia, and Australia and New
      Zealand. Cox models were used to estimate hazard ratios for coronary death,
      comparing individuals aged 55-64, 65-74, and >or=5 yrs with those aged <55 yrs.
      Adjustments were made for coronary risk factors to quantify their contributions
      to the age differential. RESULTS: During 4.1 million person-years of follow-up,
      there were 2,915 deaths from CHD. The risk of CHD increased substantially with
      age in all groups, especially in women. Differences in cardiovascular risk
      factors explained between one-quarter to one-third of the age-related excess of
      CHD in men and one-half of that in women. Systolic blood pressure was the chief
      contributor to the excess risk in all groups. CONCLUSIONS: Systolic blood
      pressure was the most important modifiable risk factor contributing to the excess
      CHD risk that occurs with aging in men and women, but in comparison with the
      effects of age itself, the effects of blood pressure are small.

PMID- 16581820
TI  - Commentary: hormones, heart disease, and the definition of hormone 'initiation'.

PMID- 16581821
TI  - Apo-AII is an elevated biomarker of chronic non-human primate ethanol self
      administration.
AB  - AIMS: Serum protein profiles were examined in naive, ethanol self-administering
      and ethanol abstinent cynomolgus monkeys (Macaca fasicularis) to search for
      differences in protein expression which could possibly serve as biomarkers of
      heavy ethanol consumption. METHODS: Surface-enhanced laser desorption ionization
      time-of-flight (SELDI-ToF) mass spectrometry was used for proteomic profiling of
      serum. RESULTS: Two proteins were identified by SELDI-ToF to be increased in
      ethanol self-administering compared with abstinent animals. These proteins were
      identified to be apolipoprotein AI (Apo-AI) and apolipoprotein AII (Apo-AII) by
      peptide mass fingerprinting and comparison with spectra of purified human Apo-AI
      and AII proteins. Immunoblot analysis of Apo-AI and Apo-AII was performed on a
      separate group of animals (within-animal ethanol-naive and self-administering)
      and confirmed a statistically significant increase in Apo-AII, while Apo-AI was
      unchanged. CONCLUSIONS: An open proteomic screen of serum and confirmation in a
      separate set of animals found Apo-AII to be increased in the serum of ethanol
      self-administering monkeys. These results are consistent with previous clinical
      studies of human ethanol consumption and serum apolipoprotein expression.
      Moreover, these results validate the use of non-human primates as a model
      organism for proteomic analysis of ethanol self-administration biomarkers.

PMID- 16581822
TI  - Expression of human DEC-205 (CD205) multilectin receptor on leukocytes.
AB  - DEC-205 (CD205) belongs to the macrophage mannose receptor family of C-type
      lectin endocytic receptors and behaves as an antigen uptake/processing receptor
      for dendritic cells (DC). To investigate DEC-205 tissue distribution in human
      leukocytes, we generated a series of anti-human DEC-205 monoclonal antibodies
      (MMRI-5, 6 and 7), which recognized epitopes within the C-type lectin-like
      domains 1 and 2, and the MMRI-7 immunoprecipitated a single approximately 200 kDa
      band, identified as DEC-205 by mass spectrometry. MMRI-7 and another DEC-205 mAb
      (MG38), which recognized the epitope within the DEC-205 cysteine-rich and
      fibronectin type II domain, were used to examine DEC-205 expression by human
      leukocytes. Unlike mouse DEC-205, which is reported to have predominant
      expression on DC, human DEC-205 was detected by flow cytometry at relatively high
      levels on myeloid blood DC and monocytes, at moderate levels on B lymphocytes and
      at low levels on NK cells, plasmacytoid blood DC and T lymphocytes. MMRI-7
      F(ab')2 also labeled monocytes, B lymphocytes and NK cells similarly excluding
      reactivity due to non-specific binding of the mAb to FcgammaR. Tonsil mononuclear
      cells showed a similar distribution of DEC-205 staining on the leukocytes. DEC
      205-specific semiquantitative immunoprecipitation/western blot and quantitative
      reverse transcriptase-PCR analysis established that these leukocyte populations
      expressed DEC-205 protein and the cognate mRNA. Thus, human DEC-205 is expressed
      on more leukocyte populations than that were previously assumed based on mouse
      DEC-205 tissue localization studies. The broader DEC-205 tissue expression in man
      is relevant to clinical DC targeting strategies and DEC-205 functional studies.

PMID- 16581823
TI  - A novel avian homologue of CD72, chB1r, down modulates BCR-mediated activation
      signals.
AB  - The avian B cell differentiation antigen chB1 is a C-type lectin membrane protein
      most homologous to mammalian CD72. Here, we report a new chB1-related gene,
      chB1r, that is located 18 kb away the chB1 gene. The cytoplasmic domain of chB1r
      protein contains two immunoreceptor tyrosine-based inhibitory motifs (ITIMs:
      ITIM1 and 2), which are identical to those found in CD72, whereas chB1 lacks the
      second ITIM2. Although chB1 expression is restricted to the bursa and an immature
      B cell line, chB1r is highly expressed in the bursa, spleen and both immature and
      mature B cell lines, a pattern that parallels CD72 expression. SHP-1 and Grb2
      interact with phosphorylated tyrosine residues within chB1r ITIM1 and ITIM2,
      respectively. By contrast, ITIM1 of chB1 does not interact with SHP-1. Functional
      characterization using chB1r/chB1 double-deficient DT40 B cells demonstrated that
      ITIM1 in chB1r transduces a negative signal for BCR-mediated nuclear factor of
      activated T cells (NF-AT) activation and that ITIM2 attenuates this negative
      signal. This study has established chB1r as the genuine avian homologue of
      mammalian CD72, and revealed an opposing role for the two ITIMs through binding
      with SHP-1 and Grb2 for regulation of BCR-mediated NF-AT activation.

PMID- 16581824
TI  - Household demand for typhoid fever vaccines in Hue, Vietnam.
AB  - The demand function for vaccines against typhoid fever was estimated using stated
      preference data collected from a random sample of 1065 households in Hue,
      Vietnam, in 2002. These are the first estimates of private willingness-to-pay
      (WTP) and demand functions for typhoid vaccines in a developing country. Mean
      respondent WTP for a single typhoid fever vaccine ranged from USD 2.30 to USD
      4.80. Mean household WTP estimates (vaccinating all members of the household)
      ranged from USD 21 to USD 27. Demand was similar for vaccines with different
      degrees of effectiveness and intervals of duration. These results suggest a
      significant potential for private sector provision of typhoid fever vaccines in
      Hue.

PMID- 16581825
TI  - Differential regulation of hyaluronan-induced IL-8 and IP-10 in airway epithelial
      cells.
AB  - Airway epithelium is emerging as a regulator of local inflammation and immune
      responses. However, the cellular and molecular mechanisms responsible for the
      immune modulation by these cells have yet to be fully elucidated. At the cellular
      level, the hallmarks of airway inflammation are mucus gland hypertrophy with
      excess mucus production, accumulation of inflammatory mediators, inflammation in
      the airway walls and lumen, and breakdown and turnover of the extracellular
      matrix. We demonstrate that fragments of the extracellular matrix component
      hyaluronan induce inflammatory chemokine production in primary airway epithelial
      cells grown at an air-liquid interface. Furthermore, hyaluronan fragments use two
      distinct molecular pathways to induce IL-8 and IFN-gamma-inducible protein 10 (IP
      10) chemokine expression in airway epithelial cells. Hyaluronan-induced IL-8
      requires the MAP kinase pathway, whereas hyaluronan-induced IP-10 utilizes the NF
      kappaB pathway. The induction is specific to low-molecular-weight hyaluronan
      fragments as other glycosaminoglycans do not induce IL-8 and IP-10 in airway
      epithelial cells. We hypothesize that not only is the extracellular matrix a
      target of destruction in airway inflammation but it plays a critical role in
      perpetuating inflammation through the induction of cytokines, chemokines, and
      modulatory enzymes in epithelial cells. Furthermore, hyaluronan, by inducing IL-8
      and IP-10 by distinct pathways, provides a unique target for differential
      regulation of key inflammatory chemokines.

PMID- 16581826
TI  - Adjacent bronchus attenuates pulmonary arterial contractility.
AB  - Bronchus-derived relaxing factor (BrDRF) decreases contractility of newborn rat
      pulmonary arteries (PA) and is dependent on nitric oxide (NO) synthesis. In vivo,
      this factor appears to gain access via the adventitial side of the PA. However,
      the adventitia has been reported to be a barrier to NO. We studied the effect of
      an adjacent bronchus on PA contractility to norepinephrine in nine juvenile lambs
      in the presence and absence of inhibitors of the NO pathway (LNA, ODQ, and Rp-8
      Br-PET-cGMPS), cytochrome P-450 inhibitor (17-ODYA), perivascular nerve activity
      blocker (TTX), and superoxide scavenger (tiron), and following disruption of
      bronchial epithelium. We also evaluated whether BrDRF was effective on both the
      endothelial and/or adventitial side of PA. Fifth-generation PA rings with and
      without an attached bronchus were contracted in standard baths with
      norepinephrine. PA were dissected, cut open, and placed in a sided chamber in
      which adventitial and endothelial sides of the PA were exposed to unattached
      bronchus separately. Norepinephrine (10(-8) to 10(-5) M) contractions were
      expressed as a fraction of maximal KCl (118 mM) contractions. Norepinephrine
      contractions were significantly reduced by the presence of an attached bronchus,
      an effect reversed by pretreatment with LNA, ODQ, and Rp-8-Br-PET-cGMPS, and
      removal of bronchial epithelium. Unattached bronchus in the bath perfusing the
      adventitial side was effective in inhibiting the contractile response in PA. NO
      gas relaxed PA when administered on the endothelial side only. We speculate that
      BrDRF is a diffusible factor that crosses the adventitia and stimulates
      production of NO within the PA.

PMID- 16581827
TI  - Src protein tyrosine kinase family and acute inflammatory responses.
AB  - Acute inflammatory responses are one of the major underlying mechanisms for
      tissue damage of multiple diseases, such as ischemia-reperfusion injury, sepsis,
      and acute lung injury. By use of cellular and molecular approaches and transgenic
      animals, Src protein tyrosine kinase (PTK) family members have been identified to
      be essential for the recruitment and activation of monocytes, macrophages,
      neutrophils, and other immune cells. Src PTKs also play a critical role in the
      regulation of vascular permeability and inflammatory responses in tissue cells.
      Importantly, animal studies have demonstrated that small chemical inhibitors for
      Src PTKs attenuate tissue injury and improve survival from a variety of
      pathological conditions related to acute inflammatory responses. Further
      investigation may lead to the clinical application of these inhibitors as drugs
      for ischemia-reperfusion injury (such as stroke and myocardial infarction),
      sepsis, acute lung injury, and multiple organ dysfunction syndrome.

PMID- 16581828
TI  - Revisiting prostacyclin: new directions in pulmonary fibrosis and inflammation.

PMID- 16581830
TI  - The high-affinity IgE receptor (FcepsilonRI): a critical regulator of airway
      smooth muscle cells?
AB  - The airway smooth muscle (ASM) has been typically described as a contractile
      tissue, responding to neurotransmitters and inflammatory mediators. However, it
      has recently been recognized that ASM cells can also secrete cytokines and
      chemokines and express cell adhesion molecules that are important for the
      perpetuation and modulation of airway inflammation. Recent progress has revealed
      the importance of IgE Fc receptors in stimulating and modulating the function of
      these cells. In particular, the high-affinity receptor for IgE (FcepsilonRI) has
      been identified in primary human ASM cells in vitro and in vivo within bronchial
      biopsies of atopic asthmatic individuals. Moreover, activation of this receptor
      has been found to induce marked increases in the intracellular calcium
      concentrations and T helper 2 cytokines and chemokines release. This and other
      evidence discussed in this review provide an emerging view of FcepsilonR/IgE
      network as a critical modulator of ASM cell function in allergic asthma.

PMID- 16581829
TI  - Regulation of Toll-like receptor 4-induced proasthmatic changes in airway smooth
      muscle function by opposing actions of ERK1/2 and p38 MAPK signaling.
AB  - Activation of Toll-like receptors (TLRs) on immune surveillance cells in the lung
      has been implicated in the pathobiology of allergic asthma, a condition
      associated with altered airway smooth muscle (ASM) contractility. Because ASM is
      known to directly respond to various proasthmatic stimuli, the potential role of
      TLR signaling in ASM in regulating airway expression of the proasthmatic
      phenotype was investigated. Cultured human ASM cells were found to express TLR4
      and TLR9 mRNA transcripts and, whereas TLR9 stimulation had little effect, TLR4
      activation with LPS elicited significant increases in IL-6 release and evoked
      proasthmatic-like changes in the constrictor and relaxation responsiveness of
      isolated rabbit ASM tissues. Complementary studies further demonstrated that the
      ASM responses to LPS were associated with activation of the ERK1/2 and p38 MAPK
      signaling pathways, IKK-mediated activation of NF-kappaB, and coupling of
      phosphorylated ERK1/2 with the p65 subunit of NF-kappaB. Moreover, the induced NF
      kappaB activity and changes in ASM responsiveness were prevented in LPS-exposed
      ASM that were pretreated with inhibitors of ERK1/2 signaling, whereas inhibition
      of p38 MAPK augmented the proasthmatic responses to LPS. Finally, activation of
      p38 MAPK with anisomycin prevented both the LPS-induced stimulation of ERK1/2
      mediated NF-kappaB activity and associated changes in ASM responsiveness.
      Collectively, these data support the novel concept that TLR4 activation in ASM
      elicits changes in ASM function that are regulated by opposing effects of MAPK
      signaling, wherein LPS-induced ERK1/2 activation mediates NF-kappaB-dependent
      proasthmatic-like changes in ASM function, whereas coactivation of p38 MAPK
      serves to homeostatically downregulate the proasthmatic effects of ERK1/2
      activation.

PMID- 16581831
TI  - Characterization of two oxidatively modified phospholipids in mixed monolayers
      with DPPC.
AB  - The properties of two oxidatively modified phospholipids viz. 1-palmitoyl-2-(9'
      oxo-nonanoyl)-sn-glycero-3-phosphocholine (PoxnoPC) and 1-palmitoyl-2-azelaoyl-sn
      glycero-3-phosphocholine (PazePC), were investigated using a Langmuir balance,
      recording force-area (pi-A) isotherms and surface potential psi. In mixed
      monolayers with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) a progressive
      disappearance of the liquid expanded-liquid condensed transition and film
      expansion was observed with increasing content of the oxidized phospholipids. The
      above is in agreement with fluorescence microscopy of the monolayers, which
      revealed an increase in the liquid expanded region of DPPC monolayers. At a
      critical pressure pi(s) approximately 42 mN/m both Poxo- and PazePC induced a
      deflection in the pi-A isotherms, which could be rationalized in terms of
      reorientation of the oxidatively modified acyl chains into aqueous phase
      (adaptation of the so-called extended conformation), followed upon further film
      compression by solubilization of the oxidized phospholipids into the aqueous
      phase. Surface potential displayed a discontinuity at the same value of
      area/molecule, corresponding to the loss of the oxidized phospholipids from the
      monolayers. Our data support the view that lipid oxidation modifies both the
      small-scale structural dynamics of biological membranes as well as their more
      macroscopic lateral organization. Accordingly, oxidatively modified lipids can be
      expected to influence the organization and functions of membrane associated
      proteins.

PMID- 16581833
TI  - Simple models for extracting mechanical work from the ATP hydrolysis cycle.
AB  - According to the binding-zipper model, the RecA class of ATPase motors converts
      chemical energy into mechanical force by the progressive annealing of hydrogen
      bonds between the nucleotide and the catalytic pocket. The role of hydrolysis is
      to weaken the binding of products, allowing them to be released so that the cycle
      can repeat. Molecular dynamics can be used to study the unbinding process, but
      the binding process is more complex, so that inferences about it are made
      indirectly from structural, mutation, and biochemical studies. Here we present a
      series of models of varying complexity that illustrate the basic processes
      involved in force production during ATP binding. These models reveal the role of
      solvent and geometry in determining the amount of mechanical work that can be
      extracted from the binding process.

PMID- 16581832
TI  - Biophysical characterization of the enzyme I of the Streptomyces coelicolor
      phosphoenolpyruvate:sugar phosphotransferase system.
AB  - The first protein in the bacterial phosphoenolpyruvate (PEP):sugar
      phosphotransferase system is the homodimeric 60-kDa enzyme I (EI), which
      autophosphorylates in the presence of PEP and Mg2+. The conformational stability
      and structure of the EI from Streptomyces coelicolor, EI(sc), were explored in
      the absence and in the presence of its effectors by using several biophysical
      probes (namely, fluorescence, far-ultraviolet circular dichroism, Fourier
      transform infrared spectroscopy (FTIR), and differential scanning calorimetry)
      and computational approaches. The structure of EI(sc) was obtained by homology
      modeling of the isolated N- and C-terminal domains of other EI proteins. The
      experimental results indicate that at physiological pH, the dimeric EI(sc) had a
      well-folded structure; however, at low pH, EI(sc) showed a partially unfolded
      state with the features of a molten globule, as suggested by fluorescence, far
      ultraviolet circular dichroism, FTIR, and 8-anilino-1-naphthalene-sulfonic acid
      binding. The thermal stability of EI(sc), in the absence of PEP and Mg2+, was
      maximal at pH 7. The presence of PEP and Mg2+ did not change substantially the
      secondary structure of the protein, as indicated by FTIR measurements. However,
      quenching experiments and proteolysis patterns suggest conformational changes in
      the presence of PEP; furthermore, the thermal stability of EI(sc) was modified
      depending on the effector added. Our approach suggests that thermodynamical
      analysis might reveal subtle conformational changes.

PMID- 16581834
TI  - Novel changes in discoidal high density lipoprotein morphology: a molecular
      dynamics study.
AB  - ApoA-I is a uniquely flexible lipid-scavenging protein capable of incorporating
      phospholipids into stable particles. Here we report molecular dynamics
      simulations on a series of progressively smaller discoidal high density
      lipoprotein particles produced by incremental removal of
      palmitoyloleoylphosphatidylcholine via four different pathways. The starting
      model contained 160 palmitoyloleoylphosphatidylcholines and a belt of two
      antiparallel amphipathic helical lipid-associating domains of apolipoprotein
      (apo) A-I. The results are particularly compelling. After a few nanoseconds of
      molecular dynamics simulation, independent of the starting particle and method of
      size reduction, all simulated double belts of the four lipidated apoA-I particles
      have helical domains that impressively approximate the x-ray crystal structure of
      lipid-free apoA-I, particularly between residues 88 and 186. These results
      provide atomic resolution models for two of the particles produced by in vitro
      reconstitution of nascent high density lipoprotein particles. These particles,
      measuring 95 angstroms and 78 angstroms by nondenaturing gradient gel
      electrophoresis, correspond in composition and in size/shape (by negative stain
      electron microscopy) to the simulated particles with molar ratios of 100:2 and
      50:2, respectively. The lipids of the 100:2 particle family form minimal surfaces
      at their monolayer-monolayer interface, whereas the 50:2 particle family displays
      a lipid pocket capable of binding a dynamic range of phospholipid molecules.

PMID- 16581835
TI  - Cell orientation by a microgrooved substrate can be predicted by automatic
      control theory.
AB  - Cells have the ability to measure and respond to extracellular signals like
      chemical molecules and topographical surface features by changing their
      orientation. Here, we examined the orientation of cultured human melanocytes
      exposed to grooved topographies. To predict the cells' orientation response, we
      describe the cell behavior with an automatic controller model. The predicted
      dependence of the cell response to height and spatial frequency of the grooves is
      obtained by considering the symmetry of the system (cell + substrate). One basic
      result is that the automatic controller responds to the square of the product of
      groove height and spatial frequency or to the aspect ratio for symmetric grooves.
      This theoretical prediction was verified by the experiments, in which melanocytes
      were exposed to microfabricated poly(dimethylsiloxane) substrates having parallel
      rectangular grooves of heights (h) between 25 and 200 nm and spatial frequencies
      (L) between 100 and 500 mm(-1). In addition, the model of the cellular automatic
      controller is extended to include the case of different guiding signals acting
      simultaneously.

PMID- 16581836
TI  - Quantification of alpha-synuclein binding to lipid vesicles using fluorescence
      correlation spectroscopy.
AB  - Alpha-synuclein (alphaS) is a soluble synaptic protein that is the major
      proteinaceous component of insoluble fibrillar Lewy body deposits that are the
      hallmark of Parkinson's disease. The interaction of alphaS with synaptic vesicles
      is thought to be critical both to its normal function as well as to its
      pathological role in Parkinson's disease. We demonstrate the use of fluorescence
      correlation spectroscopy as a tool for rapid and quantitative analysis of the
      binding of alphaS to large unilamellar vesicles of various lipid compositions. We
      find that alphaS binds preferentially to vesicles containing acidic lipids, and
      that this interaction can be blocked by increasing the concentration of NaCl in
      solution. Negative charge is not the only factor determining binding, as we
      clearly observe binding to vesicles composed entirely of zwitterionic lipids.
      Additionally, we find enhanced binding to lipids with less bulky headgroups.
      Quantification of the protein-to-lipid ratio required for binding to different
      lipid compositions, combined with other data in the literature, yields an upper
      bound estimate for the number of lipid molecules required to bind each individual
      molecule of alphaS. Our results demonstrate that fluorescence correlation
      spectroscopy provides a powerful tool for the quantitative characterization of
      alphaS-lipid interactions.

PMID- 16581838
TI  - Thermodynamics of lipid membrane solubilization by sodium dodecyl sulfate.
AB  - We provide a comprehensive thermodynamic description of lipid membrane
      dissolution by a charged detergent. To this end, we have studied the interactions
      between the anionic detergent sodium dodecyl sulfate (SDS) and the zwitterionic
      phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) in dilute
      aqueous solution (10 mM phosphate buffer, 154 mM NaCl, pH 7.4). Thermodynamic
      parameters of vesicle solubilization and reconstitution, membrane partitioning,
      and micelle formation were assessed by right-angle light scattering and
      isothermal titration calorimetry. Membrane translocation and dissolution proceed
      very slowly at 25 degrees C but are considerably accelerated at 65 degrees C. At
      this temperature, a simple SDS/POPC phase diagram (comprising vesicular,
      coexistence, and micellar ranges) and a complete set of partition coefficients
      and transfer enthalpies were obtained. Electrostatic repulsion effects at the
      membrane surface were implemented by combining Gouy-Chapman theory with a
      Langmuir adsorption isotherm to account for Na+ binding to membrane-incorporated
      DS-. This approach offered a quantitative understanding of solubilization and
      reconstitution processes, which were interpreted in terms of partition equilibria
      between and ideal mixing in all phases. More than any other property, the
      transbilayer flip-flop rate under given experimental conditions hence appears to
      dictate a detergent's suitability for thermodynamically controlled lipid membrane
      solubilization and reconstitution.

PMID- 16581837
TI  - Conformational heterogeneity in RNA polymerase observed by single-pair FRET
      microscopy.
AB  - Kinetic, structural, and single-molecule transcription measurements suggest that
      RNA polymerase can adopt many different conformations during elongation. We have
      measured the geometry of the DNA and RNA in ternary elongation complexes using
      single-pair fluorescence resonance energy transfer. Six different synthetic
      transcription elongation complexes were constructed from DNA containing an
      artificial transcription bubble, an RNA primer, and core RNA polymerase from
      Escherichia coli. Two different RNA primers were used, an 8-mer and a 5'-extended
      11-mer. Fluorescent dye labels were attached at one of three positions on the DNA
      and at the RNA primer 5'-end. Structurally, the upstream DNA runs perpendicular
      to the proposed RNA exit channel. Upon nucleoside-triphosphate addition, DNA/RNA
      hybrid separation occurs readily in the 11-mer complexes but not in the 8-mer
      complexes. Clear evidence was obtained that RNA polymerase exists in multiple
      conformations among which it fluctuates.

PMID- 16581839
TI  - Kinetics of insulin aggregation: disentanglement of amyloid fibrillation from
      large-size cluster formation.
AB  - Kinetics of human insulin aggregation has been studied at pH 1.6 and 60 degrees
      C, when amyloid fibrils are formed. We developed a novel approach based on the
      analysis of scattered light intensity distribution, which allows distinguishing
      between small and large size aggregates. By this method, we observed an
      exponential growth of fibrillar aggregates implying a heterogeneous aggregation
      mechanism. Also, the apparent lag time observed, correlated with the major
      increase of thioflavin T fluorescence, has been assigned to the onset of large
      size cluster formation.

PMID- 16581840
TI  - Limitation of cell adhesion by the elasticity of the extracellular matrix.
AB  - Cell/matrix adhesions are modulated by cytoskeletal or external stresses and
      adapt to the mechanical properties of the extracellular matrix. We propose that
      this mechanosensitivity arises from the activation of a mechanosensor located
      within the adhesion itself. We show that this mechanism accounts for the observed
      directional growth of focal adhesions and the reduction or even cessation of
      their growth when cells adhere to a soft extracellular matrix. We predict
      quantitatively that both the elasticity and the thickness of the matrix play a
      key role in the dynamics of focal adhesions. Two different types of dynamics are
      expected depending on whether the thickness of the matrix is of order of or much
      larger than the adhesion size. In the latter situation, we predict that the
      adhesion region reaches a saturation size that can be tuned by the mechanical
      properties of the matrix.

PMID- 16581841
TI  - Probing single-cell micromechanics in vivo: the microrheology of C. elegans
      developing embryos.
AB  - Cells are not directly accessible in vivo and therefore their mechanical
      properties cannot be measured by methods that require a direct contact between
      probe and cell. Here, we introduce a novel in vivo assay based on particle
      tracking microrheology whereby the extent and time-lag dependence of the mean
      squared displacements of thermally excited nanoparticles embedded within the
      cytoplasm of developing embryos reflect local viscoelastic properties. As a proof
      of principle, we probe local viscoelastic properties of the cytoplasm of
      developing Caenorhabditis elegans embryos. Our results indicate that unlike
      differentiated cells, the cytoplasm of these embryos does not exhibit measurable
      elasticity, but is highly viscous. Furthermore, the viscosity of the cytoplasm
      does not vary along the anterior-posterior axis of the embryo during the first
      cell division. These results support the hypothesis that the asymmetric
      positioning of the mitotic spindle stems from an asymmetric distribution of
      elementary force generators as opposed to asymmetric viscosity of the cytoplasm.

PMID- 16581842
TI  - Design of minimally strained nucleic Acid nanotubes.
AB  - A practical theoretical framework is presented for designing and classifying
      minimally strained nucleic acid nanotubes. The structures are based on the double
      crossover motif where each double-helical domain is connected to each of its
      neighbors via two or more Holliday-junction-like reciprocal exchanges, such that
      each domain is parallel to the main tube axis. Modeling is based on a five
      parameter characterization of the segmented double-helical structure. Once the
      constraint equations have been derived, the primary design problem for a
      minimally strained N-domain structure is reduced to solving three simultaneous
      equations in 2N+2 variables. Symmetry analysis and tube merging then allow for
      the design of a wide variety of tubes, which can be tailored to satisfy
      requirements such as specific inner and outer radii, or multiple lobed
      structures. The general form of the equations allows similar techniques to be
      applied to various nucleic acid helices: B-DNA, A-DNA, RNA, DNA-PNA, or others.
      Possible applications for such tubes include nanoscale scaffolding as well as
      custom-shaped enclosures for other nano-objects.

PMID- 16581843
TI  - Strength of multiple parallel biological bonds.
AB  - Multivalent interactions play a critical role in a variety of biological
      processes on both molecular and cellular levels. We have used molecular force
      spectroscopy to investigate the strength of multiple parallel peptide-antibody
      bonds using a system that allowed us to determine the rupture forces and the
      number of ruptured bonds independently. In our experiments the interacting
      molecules were attached to the surfaces of the probe and sample of the atomic
      force microscope with flexible polymer tethers, and the unique mechanical
      signatures of the tethers determined the number of ruptured bonds. We show that
      the rupture forces increase with the number of interacting molecules and that the
      measured forces obey the predictions of a Markovian model for the strength of
      multiple parallel bonds. We also discuss the implications of our results to the
      interpretation of force spectroscopy measurements in multiple bond systems.

PMID- 16581844
TI  - Thermodynamic comparison of the interactions of cholesterol with unsaturated
      phospholipid and sphingomyelins.
AB  - A comparative analysis of the interaction of cholesterol (Chol) with palmitoyl
      oleoyl-phosphatidylcholine (POPC) and sphingomyelins (SM) was performed in
      largely homogeneous, fluid-phase membranes at 50 degrees C. To this end, three
      independent assays for isothermal titration calorimetry were applied to
      POPC/SM/Chol mixtures. Cholesterol is solubilized by randomly methylated-beta
      cyclodextrin and the uptake of Chol into (or release from) large unilamellar
      vesicles is measured. The affinity of Chol to a POPC/SM (1:1) membrane with 30
      mol % Chol is approximately two times higher than to POPC alone; extrapolation to
      pure SM yields an affinity ratio of R(K) approximately 5. Bringing Chol in
      contact with SM is highly exothermic (-7 kJ/mol for POPC/SM (1:1), and -13 kJ/mol
      extrapolated to pure SM, both compared to POPC). No pronounced differences were
      observed between egg, bovine brain, and palmitoyl SM. With decreasing Chol
      content, R(K) increases and deltaH becomes more exothermic, suggesting a trend
      toward superlattice formation. That SM/Chol-interactions are enthalpically
      favorable implies that the preference of Chol for SM increases upon cooling and
      can induce domain formation below a certain temperature. The enthalpy gain is
      partially compensated by a loss in entropy in accordance with the concept of Chol
      induced chain ordering, which improves intermolecular interactions (van der
      Waals, H-bond) but reduces conformational and motional freedom. The ability of
      cyclodextrin to extract sphingomyelin from membranes is twofold-weaker than for
      POPC.

PMID- 16581845
TI  - Biophysical properties of the apoptosis-inducing plasma membrane voltage
      dependent anion channel.
AB  - Ion channels in the plasma membrane play critical roles in apoptosis. In a recent
      study we found that a voltage-dependent anion channel in the plasma membrane
      (VDACpl) of neuronal hippocampal cell line (HT22) cells was activated during
      apoptosis and that channel block prevented apoptosis. Whether or not VDACpl is
      identical to the mitochondrial VDACmt has been debated. Here, we biophysically
      characterize the apoptosis-inducing VDACpl and compare it with other reports of
      VDACpls and VDACmt. Excised membrane patches of apoptotic HT22 cells were studied
      with the patch-clamp technique. VDACpl has a large main-conductance state (400
      pS) and occasionally subconductance states of approximately 28 pS and 220 pS. The
      small subconductance state is associated with long-lived inactivated states, and
      the large subconductance state is associated with excision of the membrane patch
      and subsequent activation of the channel. The open-probability curve is bell
      shaped with its peak around 0 mV and is blocked by 30 microM Gd3+. The gating can
      be described by a symmetrical seven-state model with one open state and six
      closed or inactivated states. These channel properties are similar to those of
      VDACmt and other VDACpls and are discussed in relation to apoptosis.

PMID- 16581846
TI  - Origins of proton transport behavior from selectivity domain mutations of the
      aquaporin-1 channel.
AB  - The permeation free-energy profile and maximum ion conductance of proton
      transport along the channel of three aquaporin-1 (AQP1) mutants (H180A/R195V,
      H180A, and R195V) are calculated via molecular dynamics simulations and Poisson
      Nernst-Planck theory. The proton dynamics was described by the multistate
      empirical valence bond (MS-EVB) model. The results reveal three major
      contributions to the overall free-energy barrier for proton transport in AQP1:
      1), the bipolar field, 2), the electrostatic repulsion due to the Arg-195
      residue, and 3), the dehydration penalty due to the narrow channel pore. The
      double mutation (H180A/R195V) drastically drops the overall free-energy barrier
      by roughly 20 kcal/mol via simultaneously relaxing the direct electrostatic
      interaction (by R195V) and dehydration effect (by H180A).

PMID- 16581847
TI  - Prion disease: exponential growth requires membrane binding.
AB  - A hallmark feature of prions, whether in mammals or yeast and fungi, is
      exponential growth associated with fission or autocatalysis of protein
      aggregates. We have employed a rigorous kinetic analysis to recent data from
      transgenic mice lacking a glycosylphosphatidylinositol membrane anchor to the
      normal cellular PrP(C) protein, which show that toxicity requires the membrane
      binding. We find as well that the membrane is necessary for exponential growth of
      prion aggregates; without it, the kinetics is simply the quadratic-in-time growth
      characteristic of linear elongation as observed frequently in in vitro amyloid
      growth experiments with other proteins. This requires both: i), a substantial
      intercellular concentration of anchorless PrP(C), and ii), a concentration of
      small scrapies seeding aggregates from the inoculum, which remains relatively
      constant with time and exceeds the concentration of large polymeric aggregates.
      We also can explain via this analysis why mice heterozygous for the anchor
      full/anchor-free PrP(C) proteins have more rapid incubation than mice
      heterozygous for anchor-full/null PrP(C), and contrast the mammalian membrane
      associated fission or autocatalysis with the membrane free fission of yeast and
      fungal prions.

PMID- 16581848
TI  - Conformational and dynamical properties of disaccharides in water: a molecular
      dynamics study.
AB  - Explicit-solvent molecular dynamics simulations (50 ns, 300 K) of the eight
      reducing glucose disaccharides (kojibiose, sophorose, nigerose, laminarabiose,
      maltose, cellobiose, isomaltose, and gentiobiose) have been carried out using the
      GROMOS 45A4 force field (including a recently reoptimized carbohydrate parameter
      set), to investigate and compare their conformational preferences, intramolecular
      hydrogen-bonding patterns, torsional dynamics, and configurational entropies. The
      calculated average values of the glycosidic torsional angles agree well with
      available experimental data, providing validation for the force field and
      simulation methodology employed in this study. These simulations show in
      particular that: 1) (1-->6)-linked disaccharides are characterized by an
      increased flexibility, the absence of any persistent intramolecular hydrogen bond
      and a significantly higher configurational entropy (compared to the other
      disaccharides); 2) cellobiose presents a highly persistent interresidue hydrogen
      bond and a significantly lower configurational entropy (compared to the other
      disaccharides); 3) persistent hydrogen bonds are observed for all disaccharides
      (except (1-->6)-linked) and typically involve a hydrogen donor in the reducing
      residue and an acceptor in the nonreducing one; 4) the probability distributions
      associated with the glycosidic dihedral angles and psi are essentially unimodal
      for all disaccharides, and full rotation around these angles occurs at most once
      or twice for (never for psi) on the 50-ns timescale; and 5) the timescales
      associated with torsional transitions (except around and psi) range from
      approximately 30 ps (rotation of hydroxyl groups) to the nanosecond range
      (rotation of the lactol and hydroxymethyl groups, and around the omega-glycosidic
      dihedral angle in (1-->6)-linked disaccharides).

PMID- 16581851
TI  - Modelling malic acid accumulation in fruits: relationships with organic acids,
      potassium, and temperature.
AB  - Malic acid production, degradation, and storage during fruit development have
      been modelled. The model assumes that malic acid content is determined
      essentially by the conditions of its storage in the mesocarp cells, and provides
      a simplified representation of the mechanisms involved in the accumulation of
      malate in the vacuole and their regulation by thermodynamic constraints. Solving
      the corresponding system of equations made it possible to predict the malic acid
      content of the fruit as a function of organic acids, potassium concentration, and
      temperature. The model was applied to peach fruit, and parameters were estimated
      from the data of fruit development monitored over 2 years. The predictions were
      in good agreement with experimental data. Simulations were performed to analyse
      the behaviour of the model in response to variations in composition and
      temperature.

PMID- 16581850
TI  - The crystal structure at 1.5 angstroms resolution of an RNA octamer duplex
      containing tandem G.U basepairs.
AB  - The crystal structure of the RNA octamer, 5'-GGCGUGCC-3' has been determined from
      x-ray diffraction data to 1.5 angstroms resolution. In the crystal, this
      oligonucleotide forms five self-complementary double-helices in the asymmetric
      unit. Tandem 5'GU/3'UG basepairs comprise an internal loop in the middle of each
      duplex. The NMR structure of this octameric RNA sequence is also known, allowing
      comparison of the variation among the five crystallographic duplexes and the
      solution structure. The G.U pairs in the five duplexes of the crystal form two
      direct hydrogen bonds and are stabilized by water molecules that bridge between
      the base of guanine (N2) and the sugar (O2') of uracil. This contrasts with the
      NMR structure in which only one direct hydrogen bond is observed for the G.U
      pairs. The reduced stability of the r(CGUG)2 motif relative to the r(GGUC)2 motif
      may be explained by the lack of stacking of the uracil bases between the Watson
      Crick and G.U pairs as observed in the crystal structure.

PMID- 16581849
TI  - Analysis of a generic model of eukaryotic cell-cycle regulation.
AB  - We propose a protein interaction network for the regulation of DNA synthesis and
      mitosis that emphasizes the universality of the regulatory system among
      eukaryotic cells. The idiosyncrasies of cell cycle regulation in particular
      organisms can be attributed, we claim, to specific settings of rate constants in
      the dynamic network of chemical reactions. The values of these rate constants are
      determined ultimately by the genetic makeup of an organism. To support these
      claims, we convert the reaction mechanism into a set of governing kinetic
      equations and provide parameter values (specific to budding yeast, fission yeast,
      frog eggs, and mammalian cells) that account for many curious features of cell
      cycle regulation in these organisms. Using one-parameter bifurcation diagrams, we
      show how overall cell growth drives progression through the cell cycle, how cell
      size homeostasis can be achieved by two different strategies, and how mutations
      remodel bifurcation diagrams and create unusual cell-division phenotypes. The
      relation between gene dosage and phenotype can be summarized compactly in two
      parameter bifurcation diagrams. Our approach provides a theoretical framework in
      which to understand both the universality and particularity of cell cycle
      regulation, and to construct, in modular fashion, increasingly complex models of
      the networks controlling cell growth and division.

PMID- 16581852
TI  - Can a broken barrier be repaired?

PMID- 16581853
TI  - Understanding pulpitis.

PMID- 16581854
TI  - Why stretched muscles hurt--is there a role for half-sarcomere dynamics?

PMID- 16581855
TI  - Glucagon activates Ca2+ and Cl- channels in rat hepatocytes.
AB  - Glucagon is one of the major hormonal regulators of glucose metabolism,
      counteracting the hepatic effects of insulin when the concentration of glucose in
      the bloodstream falls below a certain level. Glucagon also regulates bile flow,
      hepatocellular volume and membrane potential of hepatocytes. It is clear that
      changes in cell volume and membrane potential cannot occur without significant
      ion fluxes across the plasma membrane. The effects of glucagon on membrane
      currents in hepatocytes, however, are not well understood. Here we show, by patch
      clamping of rat hepatocytes, that glucagon activates two types of currents: a
      small inwardly rectifying Ca2+ current with characteristics similar to those of
      the store-operated Ca2+ current and a larger outwardly rectifying Cl- current
      similar to that activated by cell swelling. We show that the mechanism of
      glucagon action on membrane conductance involves phospholipase C and adenylyl
      cyclase. Contribution of the adenylyl cyclase-dependent pathway to activation of
      the currents depended on Epac (exchange protein directly activated by cAMP), but
      not on protein kinase A. The activation of Ca2+ and Cl- channels is likely to
      play a key role in the mechanisms by which glucagon regulates hepatocyte
      metabolism and volume.

PMID- 16581856
TI  - 2B synaptic or extrasynaptic determines signalling from the NMDA receptor.

PMID- 16581857
TI  - Heat stress enhances arterial baroreflex control of muscle sympathetic nerve
      activity via increased sensitivity of burst gating, not burst area, in humans.
AB  - The relationship between muscle sympathetic nerve activity (MSNA) and diastolic
      blood pressure has been used to describe two sites for arterial baroreflex
      control of MSNA. By determining both the likelihood of occurrence for sympathetic
      bursts and the area of each burst for a given diastolic blood pressure, both a
      'gating' and an 'area' control site has been described in normothermic humans.
      Assessing the effect of heat stress on these mechanisms will improve the
      understanding of baroreflex control of arterial blood pressure under this thermal
      condition. Therefore, the purpose of this study was to test the hypothesis that
      heat stress enhances arterial baroreflex control of burst gating and area. In 10
      normotensive subjects (age, 32+/-2 years; mean+/-s.e.m.), MSNA (peroneal) was
      assessed using standard microneurographic techniques. Five minute periods of data
      were examined during normothermic and whole-body heating conditions. The burst
      incidence (i.e. number of sympathetic bursts per 100 cardiac cycles) and the area
      of each burst were determined for each cardiac cycle and were placed into 3 mmHg
      intervals of diastolic blood pressure. During normotheric conditions, there was a
      moderate, negative relationship between burst incidence and diastolic blood
      pressure (slope=-2.49+/-0.38; r(2)=0.73+/-0.06; mean+/-s.e.m.), while area per
      burst relative to diastolic blood pressure exhibited a less strong relationship
      (slope=-1.13+/-0.46; r(2)=0.45+/-0.09). During whole-body heating there was an
      increase in the slope of the relationship between burst incidence and diastolic
      blood pressure (slope=-4.69+/-0.44; r(2)=0.84+/-0.03) compared to normothermia
      (P<0.05), while the relationship between area per burst and diastolic blood
      pressure was unchanged (slope=-0.92+/-0.29; r(2)=0.41+/-0.08) (P=0.50). The
      primary finding of this investigation is that, at rest, whole-body heating
      enhanced arterial baroreflex control of MSNA through increased sensitivity of a
      'gating' mechanism, as indicated by an increase in the slope of the relationship
      between burst incidence and diastolic blood pressure. This occurrence is likely
      to afford protection against potential decreases in arterial blood pressure in an
      effort to preserve orthostatic tolerance during heat stress.

PMID- 16581858
TI  - Influence of ipsilateral transcranial magnetic stimulation on the triphasic EMG
      pattern accompanying fast ballistic movements in humans.
AB  - Fast ballistic flexion movements of the wrist are produced by a triphasic pattern
      of electromyographic (EMG) activity in flexor and extensor muscle. Whereas it is
      generally accepted that the primary motor cortex generates the first agonist
      burst (AG1), its contribution to the following antagonist burst (ANT) and second
      agonist burst (AG2) is unresolved. We applied single pulses of suprathreshold
      transcranial magnetic stimulation (TMS) at different times to the motor cortex
      ipsilateral to wrist flexion. This produced interhemispheric inhibition of the
      opposite motor cortex and a silent period in the ballistic EMG pattern that
      started about 30 ms after the stimulus and lasted for a further 30 ms. If the
      silence was timed to start within the first 30 ms of AG1, then timing of the
      subsequent ANT and AG2 bursts was delayed. However, if the silence began later,
      then the timing of the ANT burst was not changed. A similar effect on the onset
      latency of the AG2 was seen if the silence began in the first part of the ANT
      burst. The results are compatible with a model in which the triphasic pattern is
      not triggered as a single entity. Instead we suggest that each burst has its own
      trigger that occurs about 30-40 ms after the start of AG1 (or ANT). If AG1 (or
      ANT) is interrupted within this time period then this trigger, and hence later
      bursts, are delayed. If the interruption occurs after 30-40 ms it has no effect
      on the onset of later bursts since they have already been triggered.

PMID- 16581859
TI  - Startle responses elicited by whiplash perturbations.
AB  - The human startle response produces muscle contractions throughout the body but
      the most brisk and synchronized contractions appear in the neck muscles. This
      response, which is greatest with the first exposure to a startling stimulus,
      could produce excessive and inappropriately directed muscle contractions that
      could explain the higher incidence of whiplash injuries in people who are
      unprepared for the collision. This study seeks neurophysiological evidence of
      startle responses in the neck muscles of 120 healthy subjects exposed to between
      1 and 16 rear-end impacts or forward perturbations of different speeds. Startle
      responses were quantified by the synchronous electromyographic (EMG) activity
      between 10 and 20 Hz in bilaterally homologous sternocleidomastoid, scalene and
      cervical paraspinal neck muscles. Coherence analyses of EMGs from the left and
      right muscles were used to estimate synchrony for: (i) the first unexpected
      trial, (ii) subsequent habituated trials, and (iii) the superposition of
      habituated trials and a loud acoustic stimulus (40 ms, 124 dB sound). The peak in
      coherent EMG activity between contralateral muscle pairs in the 10-20 Hz
      bandwidth was related to startle. Synchrony in this bandwidth was observed
      between the left and right muscles during the first impact or whiplash-like
      perturbation. This synchrony decreased significantly in the habituated trials,
      but reappeared when the loud acoustic stimulus was introduced. Its presence in
      the first trial indicates that startle is part of the neuromuscular response to
      an unexpected rear-end impact. This startle component of the neuromuscular
      response could play a role in the aetiology of whiplash injuries.

PMID- 16581860
TI  - Cartilage elasticity resides in shape module decoran and aggrecan sumps of
      damping fluid: implications in osteoarthrosis.
AB  - Cartilage ultrastructure is based on collagen fibrils tied together by
      proteoglycans (PGs). Interfibrillar orthogonal PG bridges ('shape modules') were
      located by electron histochemistry using Cupromeronic blue methodology. Their
      frequency and size, similar to those in tendon, cornea, etc., were compatible
      with biochemical estimates of tissue decoran (formerly decorin), the PG component
      of shape module bridges. Digestion by hyaluronanase and chondroitinase AC helped
      to identify aggrecan and decoran and exemplified the destruction of shape modular
      organization by glycan-splitting agents. The anionic glycosaminoglycan (AGAG) of
      decoran, dermochondan sulphate (DS, formerly dermatan sulphate), contains L
      iduronate, an elastic sugar unit. Chondroitan, keratan (present in aggrecan) and
      hyaluronan are not similarly elastic but can participate in sliding-filament
      reversible deformability. Mechanical properties predicted for the interfibrillar
      bridges accord with anisotropic stress/strain responses of articular cartilage to
      compressive or tensile stresses. We propose that fluid from pericellular aggrecan
      rich domains moves under pressure into the interterritorial fibrillar arrays
      against the elastic resistance of the shape modules, which return the fluid, post
      compression, to its original position. Cartilage is tendon-like, with the
      addition of expansile aggrecan-rich reservoirs of aqueous shock absorber fluid.
      Rupture or loss of interfibrillar ties would allow expansile PG to force the
      collagenous matrix apart, imbibing water, increasing swelling and fissuring-
      characteristic manifestations of osteoarthrosis (OA), a joint disease of major
      economic importance. Decoran may be a primary target of the OA disease process.

PMID- 16581861
TI  - Effects of female steroid hormones on A-type K+ currents in murine colon.
AB  - Idiopathic constipation is higher in women of reproductive age than
      postmenopausal women or men, suggesting that female steroid hormones influence
      gastrointestinal motility. How female hormones affect motility is unclear.
      Colonic motility is regulated by ion channels in colonic myocytes. Voltage
      dependent K(+) channels serve to set the excitability of colonic muscles. We
      investigated regulation of Kv 4.3 channel expression in response to acute or
      chronic changes in female hormones. Patch clamp experiments and quantitative PCR
      were used to compare outward currents and transcript expression in colonic
      myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of
      ovariectomized mice received injections of oestrogen or progesterone to
      investigate the effects of hormone replacement. The capacitance of colonic
      myocytes from non-pregnant females was larger than in males. Net outward current
      density in male and ovariectomized mice was higher than in non-pregnant females
      and oestrogen-treated ovariectomized mice. Current densities in late pregnancy
      were lower than in female controls. Progesterone had no effect on outward
      currents. A-type currents were decreased in non-pregnant females compared with
      ovariectomized mice, and were further decreased by pregnancy or oestrogen
      replacement. Kv 4.3 transcripts did not differ significantly between groups;
      however, expression of the potassium channel interacting protein KChIP1 was
      elevated in ovariectomized mice compared with female controls and oestrogen
      treated ovariectomized mice. Delayed rectifier currents were not affected by
      oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are
      important for regulating excitability. These observations suggest a possible link
      between female hormones and altered colonic motility associated with menses,
      pregnancy and menopause.

PMID- 16581862
TI  - Creatine supplementation augments the increase in satellite cell and myonuclei
      number in human skeletal muscle induced by strength training.
AB  - The present study investigated the influence of creatine and protein
      supplementation on satellite cell frequency and number of myonuclei in human
      skeletal muscle during 16 weeks of heavy-resistance training. In a double-blinded
      design 32 healthy, male subjects (19-26 years) were assigned to strength training
      (STR) while receiving a timed intake of creatine (STR-CRE) (n=9), protein (STR
      PRO) (n=8) or placebo (STR-CON) (n=8), or serving as a non-training control group
      (CON) (n=7). Supplementation was given daily (STR-CRE: 6-24 g creatine
      monohydrate, STR-PRO: 20 g protein, STR-CON: placebo). Furthermore, timed
      protein/placebo intake were administered at all training sessions. Muscle
      biopsies were obtained at week 0, 4, 8 (week 8 not CON) and 16 of resistance
      training (3 days per week). Satellite cells were identified by
      immunohistochemistry. Muscle mean fibre (MFA) area was determined after
      histochemical analysis. All training regimes were found to increase the
      proportion of satellite cells, but significantly greater enhancements were
      observed with creatine supplementation at week 4 (compared to STR-CON) and at
      week 8 (compared to STR-PRO and STR-CON) (P<0.01-0.05). At week 16, satellite
      cell number was no longer elevated in STR-CRE, while it remained elevated in STR
      PRO and STR-CON. Furthermore, creatine supplementation resulted in an increased
      number of myonuclei per fibre and increases of 14-17% in MFA at week 4, 8 and 16
      (P<0.01). In contrast, STR-PRO showed increase in MFA only in the later (16 week,
      +8%) and STR-CON only in the early (week 4, +14%) phases of training,
      respectively (P<0.05). In STR-CRE a positive relationship was found between the
      percentage increases in MFA and myonuclei from baseline to week 16, respectively
      (r=0.67, P<0.05). No changes were observed in the control group (CON). In
      conclusion, the present study demonstrates for the first time that creatine
      supplementation in combination with strength training amplifies the training
      induced increase in satellite cell number and myonuclei concentration in human
      skeletal muscle fibres, thereby allowing an enhanced muscle fibre growth in
      response to strength training.

PMID- 16581863
TI  - Topographical heterogeneity of K(IR) currents in pericyte-containing microvessels
      of the rat retina: effect of diabetes.
AB  - Although inwardly rectifying potassium (K(IR)) channels are known to have
      important functional roles in arteries and arterioles, knowledge of these
      channels in pericyte-containing microvessels is limited. A working hypothesis is
      that K(IR) channel activity affects the membrane potential and thereby the
      contractile tone of abluminal pericytes whose contractions and relaxations may
      regulate capillary perfusion. Because pericyte function is thought to be
      particularly important in the retina, we used the perforated-patch technique to
      monitor the ionic currents of pericytes located on microvessels freshly isolated
      from the rat retina. In addition, because changes in ion channel function may
      contribute to microvascular dysfunction in the diabetic retina, we also recorded
      from pericyte-containing microvessels of streptozotocin-injected rats. Using
      barium to identify K(IR) currents, we found that there is a topographical
      heterogeneity of these currents in the pericyte-containing microvasculature of
      the normal retina. Specifically, the K(IR) current detected at distal locations
      is strongly rectifying, but the proximal K(IR) current is weakly rectifying and
      has a smaller inward conductance. However, soon after the onset of diabetes,
      these differences diminish as the rectification and inward conductance of the
      proximal K(IR) current increase. These diabetes-induced changes were reversed by
      an inhibitor of polyamine synthesis and could be mimicked by spermine, whose
      concentration is elevated in the diabetic eye. Hence, spermine is a candidate for
      mediating the effect of diabetes on the function of microvascular K(IR) channels.
      In addition, our findings raise the possibility that functional changes in K(IR)
      channels contribute to blood flow dysregulation in the diabetic retina.

PMID- 16581864
TI  - Maximal exercise and muscle oxygen extraction in acclimatizing lowlanders and
      high altitude natives.
AB  - The tight relation between arterial oxygen content and maximum oxygen uptake
      (Vv(o2max)within a given person at sea level is diminished with altitude
      acclimatization. An explanation often suggested for this mismatch is impairment
      of the muscle O(2) extraction capacity with chronic hypoxia, and is the focus of
      the present study. We have studied six lowlanders during maximal exercise at sea
      level (SL) and with acute (AH) exposure to 4,100 m altitude, and again after 2
      (W2) and 8 weeks (W8) of altitude sojourn, where also eight high altitude native
      (Nat) Aymaras were studied. Fractional arterial muscle O(2) extraction at maximal
      exercise was 90.0+/-1.0% in the Danish lowlanders at sea level, and remained
      close to this value in all situations. In contrast to this, fractional arterial
      O(2) extraction was 83.2+/-2.8% in the high altitude natives, and did not change
      with the induction of normoxia. The capillary oxygen conductance of the lower
      extremity, a measure of oxygen diffusing capacity, was decreased in the Danish
      lowlanders after 8 weeks of acclimatization, but was still higher than the value
      obtained from the high altitude natives. The values were (in ml min(-1) mmHg(-1))
      55.2+/-3.7 (SL), 48.0+/-1.7 (W2), 37.8+/-0.4 (W8) and 27.7+/-1.5 (Nat). However,
      when correcting oxygen conductance for the observed reduction in maximal leg
      blood flow with acclimatization the effect diminished. When calculating a
      hypothetical leg V(o2max)at altitude using either the leg blood flow or the O(2)
      conductance values obtained at sea level, the former values were almost
      completely restored to sea level values. This would suggest that the major
      determinant V(o2max)for not to increase with acclimatization is the observed
      reduction in maximal leg blood flow and O(2) conductance.

PMID- 16581865
TI  - Developmental remodelling of the lemniscal synapse in the ventral basal thalamus
      of the mouse.
AB  - Synapse elimination occurs throughout the nervous system during development, and
      is essential for the formation of neural circuits. The mechanisms underlying
      synapse elimination in the brain, however, remain largely unknown. Using whole
      cell patch-clamp recording in a slice preparation, we examined synaptic
      refinement at the somatosensory relay synapse (lemniscal synapse) in the ventral
      basal thalamus of the mouse during postnatal development. At 1 week old, each
      neuron in the ventral basal thalamus is innervated by multiple lemniscal fibres,
      as revealed by multiple increments of the synaptic response. By 16 days after
      birth (P16), the majority of neurons showed an all-or-none response, suggesting a
      single fibre innervation. In addition to synapse elimination, extensive
      modifications in synaptic properties occur during the second week after birth.
      The ratio of AMPA to NMDA component of the synaptic current tripled between P7
      and P17. The decay constant of the NMDA component decreased by about 70% between
      P7 and P17; ifenprodil (3 microm) reduced the NMDA component by about 40% in
      neurons at P7-9, but was much less effective at P20-24. On the other hand, there
      was little change in the inward rectification of AMPA component between P11 and
      P24. Paired-pulse ratios, measured at -70 and +40 mV, were stable between P7 and
      P24. Whisker deprivation from P5 through P19 had no effect on the elimination or
      the maturation of the lemniscal synapse. These results suggest that the lemniscal
      synapse in the ventral basal thalamus undergoes extensive refinement during the
      second week, and that sensory experience has a rather limited role in this
      process.

PMID- 16581867
TI  - Changes in corticospinal drive to spinal motoneurones following visuo-motor skill
      learning in humans.
AB  - We have previously demonstrated an increase in the excitability of the leg motor
      cortical area in relation to acquisition of a visuo-motor task in healthy humans.
      It remains unknown whether the interaction between corticospinal drive and spinal
      motoneurones is also modulated following motor skill learning. Here we
      investigated the effect of visuo-motor skill training involving the ankle muscles
      on the coupling between electroencephalographic (EEG) activity recorded from the
      motor cortex (Cz) and electromyographic (EMG) activity recorded from the left
      tibialis anterior (TA) muscle in 11 volunteers. Coupling in the time (cumulant
      density function) and frequency domains (coherence) between EEG-EMG and EMG-EMG
      activity were calculated during tonic isometric dorsiflexion before and after 32
      min of training a visuo-motor tracking task involving the ankle muscles or
      performing alternating dorsi- and plantarflexion movements without visual
      feedback. A significant increase in EEG-EMG coherence around 15-35 Hz was
      observed following the visuo-motor skill session in nine subjects and in only one
      subject after the control task. Changes in coherence were specific to the trained
      muscle as coherence for the untrained contralateral TA muscle was unchanged. EEG
      and EMG power were unchanged following the training. Our results suggest that
      visuo-motor skill training is associated with changes in the corticospinal drive
      to spinal motorneurones. Possibly these changes reflect sensorimotor integration
      processes between cortex and muscle as part of the motor learning process.

PMID- 16581866
TI  - Rapid inhibition of neural excitability in the nucleus tractus solitarii by
      leptin: implications for ingestive behaviour.
AB  - The fat-derived peptide leptin regulates cellular activity in areas of the CNS
      related to feeding, and application of leptin to the fourth ventricle or the
      nucleus tractus solitarii (NTS) inhibits food intake and weight gain. The
      hypothesis that leptin modulates cellular activity in the NTS was tested using
      whole-cell patch-clamp recordings in brainstem slices. Leptin caused a rapid
      membrane hyperpolarization in 58% of rat NTS neurones, including neurones
      receiving tractus solitarius input (i.e. viscerosensory) and those involved in
      regulating output to the stomach, identified after gastric inoculation with a
      transneuronal retrograde viral label. The hyperpolarization was accompanied by a
      decrease in input resistance and cellular responsiveness, reversed near the K(+)
      equilibrium potential, and was prevented by intracellular Cs(+). Perfusion of
      tolbutamide (200 microm) or wortmannin (100-200 nm) prevented the
      hyperpolarization, indicating activation of an ATP-sensitive K(+) channel via a
      PI3 kinase-dependent mechanism. Constant latency tractus solitarius-evoked EPSCs
      were decreased in amplitude by leptin, and the paired-pulse ratio was increased,
      suggesting effects on evoked EPSCs involved activation of receptors on vagal
      afferent terminals. Leptin reduced the frequency of spontaneous and miniature
      EPSCs, whereas IPSCs were largely unaffected. Leptin's effects were observed in
      neurones from lean, but not obese, Zucker rats. Neurones that expressed enhanced
      green fluorescent protein (EGFP) in a subpopulation of putative GABAergic
      neurones in transgenic mice did not respond to leptin, whereas unlabelled murine
      neurones responded similarly to rat neurones. Leptin therefore directly and
      rapidly suppresses activity of excitatory NTS neurones likely to be involved in
      viscerosensory integration and/or premotor control of the stomach.

PMID- 16581868
TI  - Temporal profile of rat skeletal muscle capillary haemodynamics during recovery
      from contractions.
AB  - In skeletal muscle capillaries, red blood cell (RBC) flux (F(RBC)), velocity
      (V(RBC)) and haematocrit (Hct(CAP)) are key determinants of microvascular O2
      exchange. However, the mechanisms leading to the changes in F(RBC), V(RBC) and
      Hct(CAP) during muscle contractions and recovery thereafter are not fully
      understood. To address this issue we used intravital microscopy to investigate
      the temporal profile of the rat spinotrapezius muscle (n = 5) capillary
      haemodynamics during recovery from 3 min of twitch muscle contractions (1 Hz, 4-6
      V). Specifically, we hypothesized that (1) during early recovery F(RBC) and
      V(RBC) would decrease rapidly and F(RBC) would display a biphasic response
      (consistent with a muscle pump effect on capillary haemodynamics), and (2) there
      would be a dynamic relationship between changes (Delta) in V(RBC) and Hct(CAP).
      The values at rest (R) and end-recovery (ER) were significantly lower (P < 0.05)
      than at end-contraction (EC) for F(RBC) (in cells s(-1), R = 30.1 +/- 7.8, EC =
      46.2 +/- 7.3 and ER = 26.0 +/- 6.1), V(RBC) (in microm s(-1), R = 368 +/- 83, EC
      = 497 +/- 62 and ER = 334 +/- 59) and Hct(CAP) (R = 0.193 +/- 0.016, EC = 0.214
      +/- 0.023 and ER = 0.185 +/- 0.019). The first data point where a significant
      decrease in F(RBC), Hct(CAP) and V(RBC) occurred was at 5, 5 and 20 s post
      contraction, respectively. The decrease in F(RBC) approximated a monoexponential
      response (half-time of approximately 26 s). The relationship between DeltaV(RBC)
      and DeltaHct(CAP) was not significant (P > 0.05). Based on the early decrease in
      F(RBC) (within 5 s), overall dynamic profile of F(RBC) and the approximately 20 s
      'delay' to the decrease in V(RBC) we conclude that the muscle pump does not
      appear to contribute substantially to the steady-state capillary haemodynamics in
      the contracting rat spinotrapezius muscle. Moreover, our findings suggest that
      alterations in V(RBC) do not obligate proportional changes in Hct(CAP) within
      individual capillaries following muscle contractions.

PMID- 16581871
TI  - The rapidly adapting receptors in mammalian airways and their responses to
      changes in extravascular fluid volume.
AB  - In this short review, we shall focus on some recent findings on the physiological
      stimulus for the rapidly adapting receptors (RAR) of the airways. They are
      readily activated by a sustained inflation of the lungs and they are usually
      identified by their rapid adaptation to this stimulus. They are also activated by
      both tactile stimuli and irritant gases applied to the epithelium of the airways.
      The investigations reviewed here suggest that these receptors are activated by
      changes in extravascular fluid volume. The principal factors governing fluid flux
      from the microcirculation are identified in the Starling equation. These are the
      hydrostatic pressure, plasma oncotic pressure and capillary permeability.
      Findings from recent studies suggest that all these factors increase the activity
      of RAR. In addition, these receptors are also activated by obstruction of lymph
      drainage from the lung. Evidence is presented to show that manipulation of
      Starling forces also increases the extravascular fluid volume of the airways in
      areas where the RAR are located. On the basis of these findings, it is suggested
      that, along with mechanosensitivity to stimuli such as stretch, inflation and
      deflation, another physiological stimulus to the RAR is a change in extravascular
      fluid volume in the regions of the airways where these receptors are located.

PMID- 16581869
TI  - Reflex regulation of airway sympathetic nerves in guinea-pigs.
AB  - Sympathetic nerves innervate the airways of most species but their reflex
      regulation has been essentially unstudied. Here we demonstrate sympathetic nerve
      mediated reflex relaxation of airway smooth muscle measured in situ in the guinea
      pig trachea. Retrograde tracing, immunohistochemistry and electrophysiological
      analysis identified a population of substance P-containing capsaicin-sensitive
      spinal afferent neurones in the upper thoracic (T1-T4) dorsal root ganglia (DRG)
      that innervate the airways and lung. After bilateral vagotomy, atropine
      pretreatment and pre-contraction of the trachealis with histamine, nebulized
      capsaicin (10-60 microm) evoked a 63+/-7% reversal of the histamine-induced
      contraction of the trachealis. Either the beta-adrenoceptor antagonist
      propranolol (2 microm, administered directly to the trachea) or bilateral
      sympathetic nerve denervation of the trachea essentially abolished these reflexes
      (10+/-9% and 6+/-4% relaxations, respectively), suggesting that they were
      mediated primarily, if not exclusively, by sympathetic adrenergic nerve
      activation. Cutting the upper thoracic dorsal roots carrying the central
      processes of airway spinal afferents also markedly blocked the relaxations (9+/
      5% relaxation). Comparable inhibitory effects were observed following intravenous
      pretreatment with neurokinin receptor antagonists (3+/-7% relaxations). These
      reflexes were not accompanied by consistent changes in heart rate or blood
      pressure. By contrast, stimulating the rostral cut ends of the cervical vagus
      nerves also evoked a sympathetic adrenergic nerve-mediated relaxation that were
      accompanied by marked alterations in blood pressure. The results indicate that
      the capsaicin-induced reflex-mediated relaxation of airway smooth muscle
      following vagotomy is mediated by sequential activation of tachykinin-containing
      spinal afferent and sympathetic efferent nerves innervating airways. This
      sympathetic nerve-mediated response may serve to oppose airway contraction
      induced by parasympathetic nerve activation in the airways.

PMID- 16581870
TI  - Tyrosine kinase and phosphatase regulation of slow delayed-rectifier K+ current
      in guinea-pig ventricular myocytes.
AB  - The objective of this study was to investigate the involvement of tyrosine
      phosphorylation in the regulation of the cardiac slowly activating delayed
      rectifier K(+) current (I(Ks)) that is important for action potential
      repolarization. Constitutive I(Ks) recorded from guinea-pig ventricular myocytes
      was suppressed by broad-spectrum tyrosine kinase (TK) inhibitors tyrphostin A23
      (IC(50), 4.1+/-0.6 microm), tyrphostin A25 (IC(50), 12.1+/-2.1 microm) and
      genistein (IC(50), 64+/-4 microm), but was relatively insensitive to the inactive
      analogues tyrphostin A1, tyrphostin A63, daidzein and genistin. I(Ks) was
      unaffected by AG1478 (10 microm), an inhibitor of epidermal growth factor
      receptor TK, and was strongly suppressed by the Src TK inhibitor PP2 (10 microm)
      but not by the inactive analogue PP3 (10 microm). The results of experiments with
      forskolin, H89 and bisindolylmaleimide I indicate that the suppression of I(Ks)
      by TK inhibitors was not mediated via inhibition of (I(Ks)-stimulatory) protein
      kinases A and C. To evaluate whether the suppression was related to lowered
      tyrosine phosphorylation, myocytes were pretreated with TK inhibitors and then
      exposed to the phosphotyrosyl phosphatase inhibitor orthovanadate (1 mm).
      Orthovanadate almost completely reversed the suppression of I(Ks) induced by
      broad-spectrum TK inhibitors at concentrations around their IC(50) values. We
      conclude that basal I(Ks) is strongly dependent on tyrosine phosphorylation of Ks
      channel (or channel-regulatory) protein.

PMID- 16581872
TI  - Adenosine affects the release of Ca2+ from the sarcoplasmic reticulum via A2A
      receptors in ferret skinned cardiac fibres.
AB  - In this study, it was shown that adenosine potentiates caffeine-induced Ca2+
      release. It was then proposed that the enhancement of the caffeine-induced Ca2+
      release might occur by a direct effect on the ryanodine Ca2+ release channel or
      on other Ca2+ regulation mechanisms. Furthermore, A2A receptors may be functional
      on the ferret cardiac sarcoplasmic reticulum. Using chemically skinned fibres,
      experiments were conducted on ferret cardiac muscle to find out whether adenosine
      and the A1 and A2A adenosine receptor agonists (CCPA and CGS 21680) and
      antagonists (DPCPX and ZM 241385) affected caffeine-induced Ca2+ release and the
      Ca2+ sensitivity of contractile proteins. Changes in the caffeine-induced
      contracture brought about by adenosine and by adenosine-receptor agonists and
      antagonists were recorded in saponin-skinned fibres (50 microg ml(-1)). Tension
      pCa relationships were then obtained by exposing Triton X-100-skinned fibres (1%
      v/v) sequentially to solutions of decreasing pCa. Adenosine (1-100 nm) and the
      specific A2A receptor agonist CGS 21680 (1-50 nm) produced a concentration
      dependant potentiation of the caffeine-induced Ca2+ release from saponin-skinned
      fibres. The data plotted versus adenosine and CGS 21680 concentrations displayed
      sigmoid relationships (Hill relationship), with potentiation of Ca2+ release by
      22.2 +/- 1.6 (n = 6) and 10.9 +/- 0.4% (n = 6), respectively. In addition, the
      potentiation of caffeine-induced Ca2+ release by adenosine (50 nm; 15.3 +/- 1.0%;
      n = 6) and by CGS 21680 (50 nm; 11.2 +/- 0.4%; n = 6) was reduced by the specific
      A2A receptor antagonist ZM 241385 (50 nm) to 8.0 +/- 1.4 (n = 4) and 5.4 +/- 1.2%
      (n = 4), respectively. The A1 receptor agonist CCPA (1-50 nm) and antagonist
      DPCPX (50 nm) had no significant effects on caffeine responses. In Triton X-100
      skinned fibres, the maximal Ca(2+)-activated tension of the contractile proteins
      (41.3 +/- 4.1 mN mm(-2); n = 8), the Hill coefficient (nH = 2.2 +/- 0.1; n = 8)
      and the pCa50 (6.15 +/- 0.05; n = 8) were not significantly modified by adenosine
      (100 nm) or by CGS 21680 (50 nm).

PMID- 16581873
TI  - Identification of a vacuolar sucrose transporter in barley and Arabidopsis
      mesophyll cells by a tonoplast proteomic approach.
AB  - The vacuole is the main cellular storage pool, where sucrose (Suc) accumulates to
      high concentrations. While a limited number of vacuolar membrane proteins, such
      as V-type H(+)-ATPases and H(+)-pyrophosphatases, are well characterized, the
      majority of vacuolar transporters are still unidentified, among them the
      transporter(s) responsible for vacuolar Suc uptake and release. In search of
      novel tonoplast transporters, we used a proteomic approach, analyzing the
      tonoplast fraction of highly purified mesophyll vacuoles of the crop plant barley
      (Hordeum vulgare). We identified 101 proteins, including 88 vacuolar and putative
      vacuolar proteins. The Suc transporter (SUT) HvSUT2 was discovered among the 40
      vacuolar proteins, which were previously not reported in Arabidopsis (Arabidopsis
      thaliana) vacuolar proteomic studies. To confirm the tonoplast localization of
      this Suc transporter, we constructed and expressed green fluorescent protein
      (GFP) fusion proteins with HvSUT2 and its closest Arabidopsis homolog, AtSUT4.
      Transient expression of HvSUT2-GFP and AtSUT4-GFP in Arabidopsis leaves and onion
      (Allium cepa) epidermal cells resulted in green fluorescence at the tonoplast,
      indicating that these Suc transporters are indeed located at the vacuolar
      membrane. Using a microcapillary, we selected mesophyll protoplasts from a leaf
      protoplast preparation and demonstrated unequivocally that, in contrast to the
      companion cell-specific AtSUC2, HvSUT2 and AtSUT4 are expressed in mesophyll
      protoplasts, suggesting that HvSUT2 and AtSUT4 are involved in transport and
      vacuolar storage of photosynthetically derived Suc.

PMID- 16581874
TI  - G-protein complex mutants are hypersensitive to abscisic acid regulation of
      germination and postgermination development.
AB  - Abscisic acid (ABA) plays regulatory roles in a host of physiological processes
      throughout plant growth and development. Seed germination, early seedling
      development, stomatal guard cell functions, and acclimation to adverse
      environmental conditions are key processes regulated by ABA. Recent evidence
      suggests that signaling processes in both seeds and guard cells involve
      heterotrimeric G proteins. To assess new roles for the Arabidopsis (Arabidopsis
      thaliana) Galpha subunit (GPA1), the Gbeta subunit (AGB1), and the candidate G
      protein-coupled receptor (GCR1) in ABA signaling during germination and early
      seedling development, we utilized knockout mutants lacking one or more of these
      components. Our data show that GPA1, AGB1, and GCR1 each negatively regulates ABA
      signaling in seed germination and early seedling development. Plants lacking AGB1
      have greater ABA hypersensitivity than plants lacking GPA1, suggesting that AGB1
      is the predominant regulator of ABA signaling and that GPA1 affects the efficacy
      of AGB1 execution. GCR1 acts upstream of GPA1 and AGB1 for ABA signaling pathways
      during germination and early seedling development: gcr1 gpa1 double mutants
      exhibit a gpa1 phenotype and agb1 gcr1 and agb1 gcr1 gpa1 mutants exhibit an agb1
      phenotype. Contrary to the scenario in guard cells, where GCR1 and GPA1 have
      opposite effects on ABA signaling during stomatal opening, GCR1 acts in concert
      with GPA1 and AGB1 in ABA signaling during germination and early seedling
      development. Thus, cell- and tissue-specific functional interaction in response
      to a given signal such as ABA may determine the distinct pathways regulated by
      the individual members of the G-protein complex.

PMID- 16581875
TI  - Maize cDNAs expressed in endosperm encode functional farnesyl diphosphate
      synthase with geranylgeranyl diphosphate synthase activity.
AB  - Isoprenoids are the most diverse and abundant group of natural products. In
      plants, farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) are
      precursors to many isoprenoids having essential functions. Terpenoids and sterols
      are derived from FPP, whereas gibberellins, carotenoids, casbenes, taxenes, and
      others originate from GGPP. The corresponding synthases (FPP synthase [FPPS] and
      GGPP synthase [GGPPS]) catalyze, respectively, the addition of two and three
      isopentenyl diphosphate molecules to dimethylallyl diphosphate. Maize (Zea mays
      L. cv B73) endosperm cDNAs encoding isoprenoid synthases were isolated by
      functional complementation of Escherichia coli cells carrying a bacterial gene
      cluster encoding all pathway enzymes needed for carotenoid biosynthesis, except
      for GGPPS. This approach indicated that the maize gene products were functional
      GGPPS enzymes. Yet, the predicted enzyme sequences revealed FPPS motifs and
      homology with FPPS enzymes. In vitro assays demonstrated that indeed these maize
      enzymes produced both FPP and GGPP and that the N-terminal sequence affected the
      ratio of FPP to GGPP. Their functionality in E. coli demonstrated that these
      maize enzymes can be coupled with a metabolon to provide isoprenoid substrates
      for pathway use, and suggests that enzyme bifunctionality can be harnessed. The
      maize cDNAs are encoded by a small gene family whose transcripts are prevalent in
      endosperm beginning mid development. These maize cDNAs will be valuable tools for
      assessing the critical structural properties determining prenyl transferase
      specificity and in metabolic engineering of isoprenoid pathways, especially in
      cereal crops.

PMID- 16581877
TI  - Regulation of flowering in the long-day grass Lolium temulentum by gibberellins
      and the FLOWERING LOCUS T gene.
AB  - Seasonal control of flowering often involves leaf sensing of daylength coupled to
      time measurement and generation and transport of florigenic signals to the shoot
      apex. We show that transmitted signals in the grass Lolium temulentum may include
      gibberellins (GAs) and the FLOWERING LOCUS T (FT) gene. Within 2 h of starting a
      florally inductive long day (LD), expression of a 20-oxidase GA biosynthetic gene
      increases in the leaf; its product, GA(20), then increases 5.7-fold versus short
      day; its substrate, GA(19), decreases equivalently; and a bioactive product,
      GA(5), increases 4-fold. A link between flowering, LD, GAs, and GA biosynthesis
      is shown in three ways: (1) applied GA(19) became florigenic on exposure to LD;
      (2) expression of LtGA20ox1, an important GA biosynthetic gene, increased in a
      florally effective LD involving incandescent lamps, but not with noninductive
      fluorescent lamps; and (3) paclobutrazol, an inhibitor of an early step of GA
      biosynthesis, blocked flowering, but only if applied before the LD. Expression
      studies of a 2-oxidase catabolic gene showed no changes favoring a GA increase.
      Thus, the early LD increase in leaf GA(5) biosynthesis, coupled with subsequent
      doubling in GA(5) content at the shoot apex, provides a substantial trail of
      evidence for GA(5) as a LD florigen. LD signaling may also involve transport of
      FT mRNA or protein because expression of LtFT and LtCONSTANS increased rapidly,
      substantially (>80-fold for FT), and independently of GA. However, because a LD
      from fluorescent lamps induced LtFT expression but not flowering, the nature of
      the light response of FT requires clarification.

PMID- 16581876
TI  - Functional characterization of ice plant SKD1, an AAA-type ATPase associated with
      the endoplasmic reticulum-Golgi network, and its role in adaptation to salt
      stress.
AB  - A salt-induced gene mcSKD1 (suppressor of K+ transport growth defect) able to
      facilitate K+ uptake has previously been identified from the halophyte ice plant
      (Mesembryanthemum crystallinum). The sequence of mcSKD1 is homologous to vacuolar
      protein sorting 4, an ATPase associated with a variety of cellular activities
      type ATPase that participates in the sorting of vacuolar proteins into
      multivesicular bodies in yeast (Saccharomyces cerevisiae). Recombinant mcSKD1
      exhibited ATP hydrolytic activities in vitro with a half-maximal rate at an ATP
      concentration of 1.25 mm. Point mutations on active site residues abolished its
      ATPase activity. ADP is both a product and a strong inhibitor of the reaction.
      ADP-binding form of mcSDK1 greatly reduced its catalytic activity. The mcSKD1
      protein accumulated ubiquitously in both vegetative and reproductive parts of
      plants. Highest accumulation was observed in cells actively engaging in the
      secretory processes, such as bladder cells of leaf epidermis. Membrane
      fractionation and double-labeling immunofluorescence showed the predominant
      localization of mcSKD1 in the endoplasmic reticulum-Golgi network. Immunoelectron
      microscopy identified the formation of mcSKD1 proteins into small aggregates in
      the cytosol and associated with membrane continuum within the endomembrane
      compartments. These results indicated that this ATPase participates in the
      endoplasmic reticulum-Golgi mediated protein sorting machinery for both
      housekeeping function and compartmentalization of excess Na+ under high salinity.

PMID- 16581879
TI  - Ethical issues involving research conducted with homebound older adults.
AB  - Conducting research in the home setting with homebound older adults presents
      distinct ethical and practical challenges that require special consideration.
      This article describes the methodological issues that make studying homebound
      older adults especially vulnerable to therapeutic misconception and researcher
      role conflict and offers practical strategies for researchers to deal with these
      problems when studying this population. In writing this article, we draw on more
      than a decade of descriptive and intervention research focusing exclusively on
      the homebound older population in which the authors have collaborated.
      Therapeutic misconception and researcher role conflict may occur because of
      methodological issues related to the recruitment of participants, the "homebound"
      status of participants, and the home setting as the interview site. Particular
      care is required on the part of the researcher to address these ethical issues.
      This may be accomplished especially through clear communication during the
      informed consent process with participants and in scientific communication with
      colleagues.

PMID- 16581878
TI  - The shoot-specific expression of gamma-glutamylcysteine synthetase directs the
      long-distance transport of thiol-peptides to roots conferring tolerance to
      mercury and arsenic.
AB  - Thiol-peptides synthesized as intermediates in phytochelatin (PC) biosynthesis
      confer cellular tolerance to toxic elements like arsenic, mercury, and cadmium,
      but little is known about their long-distance transport between plant organs. A
      modified bacterial gamma-glutamylcysteine synthetase (ECS) gene, S1ptECS, was
      expressed in the shoots of the ECS-deficient, heavy-metal-sensitive cad2-1 mutant
      of Arabidopsis (Arabidopsis thaliana). S1ptECS directed strong ECS protein
      expression in the shoots, but no ECS was detected in the roots of transgenic
      plant lines. The S1ptECS gene restored full mercury tolerance and partial cadmium
      tolerance to the mutant and enhanced arsenate tolerance significantly beyond wild
      type levels. After arsenic treatment, the root concentrations of gamma
      glutamylcysteine (EC), PC2, and PC3 peptides in a S1ptECS-complemented cad2-1
      line increased 6- to 100-fold over the mutant levels and were equivalent to wild
      type concentrations. The shoot and root levels of glutathione were 2- to 5-fold
      above those in wild-type plants, with or without treatment with toxicants. Thus,
      EC and perhaps glutathione are efficiently transported from shoots to roots. The
      possibility that EC or other PC pathway intermediates may act as carriers for the
      long-distance phloem transport and subsequent redistribution of thiol-reactive
      toxins and nutrients in plants is discussed.

PMID- 16581880
TI  - Residential care provision in Medicaid home- and community-based waivers: a
      national study of program trends.
AB  - PURPOSE: While state policy and market factors are known to have contributed to
      the increased supply of residential care, little is known about efforts to
      accommodate demand from lower-income consumers. This study describes
      participation and expenditure trends for residential care services funded by
      Medicaid waivers and examines variation across programs. DESIGN AND METHODS: We
      collected annually reported Center for Medicare and Medicaid Services (CMS) Form
      372 data from state officials for each waiver that provides residential care
      services for the period 1995 to 2002. Descriptive statistics examined waiver
      program participation and expenditures while adjusting for population changes and
      inflation. RESULTS: Between 1995 and 2002, national Medicaid waiver-funded
      residential care participants increased by almost threefold to 120,000 and
      expenditures more than quadrupled to 2.3 billion dollars. However, Medicaid
      waiver program participation and spending varied considerably by state, by target
      population, and by level of care. IMPLICATIONS: This study highlights three
      important policy concerns: (a) Medicaid-supported residents remain
      underrepresented in residential care, (b) large interstate variation persists in
      Medicaid residential care service provision, and (c) state policy choices favor
      Medicaid spending on residential care for persons with mental retardation or
      developmental disabilities.

PMID- 16581881
TI  - Characteristics associated with home- and community-based service utilization for
      Medicare managed care consumers.
AB  - PURPOSE: We identified the types of home- and community-based services (HCBS)
      that high-risk older adults in Medicare managed care used, and we examined
      participant characteristics associated with service use in six areas: overall
      service use, four specific categories of HCBS, and referrals to insured medical
      services. DESIGN AND METHODS: We used service data from the Care Advocate
      Demonstration Program, a telephone-based care-management intervention that linked
      chronically ill older adults to HCBS. Two hundred and twenty-four high-risk older
      adults who were enrolled in a southern California-based Medicare managed care
      plan received an assessment, service referrals, and 12 months of telephone follow
      up by master's level social service professionals. We used logistic regression to
      estimate the odds of using the HCBS categories and medical services. RESULTS:
      Results indicated that characteristics associated with service use varied
      extensively, depending on the service. Age, gender, social support, living
      situation, education, specific functional impairments, heart conditions, and
      sensory impairments at baseline significantly predicted utilization in the six
      different service models. IMPLICATIONS: Policy implications include the
      importance of individualized care-management assessments that direct targeted
      referrals to appropriate services. Findings support the need for individualized
      care-management assessment and service planning, suggesting that a "one size fits
      all" approach to HCBS will not meet the varied needs of diverse consumers.

PMID- 16581882
TI  - Effect of a voucher benefit on the demand for paid personal assistance.
AB  - PURPOSE: We estimated the effect of a voucher benefit on the demand for personal
      assistance by Medicare beneficiaries aged 65 years or older who had functional
      disabilities. DESIGN AND METHODS: We performed a secondary data analysis on 645
      Medicare beneficiaries from the Medicare Primary and Consumer-Directed Care
      Demonstration (a randomized controlled trial) between August 1998 and June 2000.
      We estimated a two-part model to determine the effect of the voucher on out-of
      pocket personal assistance expenditures. The model controlled for individual
      health and functional status variables, sociodemographics, prior health care
      utilization, and state fixed effects. RESULTS: A modest experimental Medicare
      personal assistance voucher benefit (that reimbursed 80% of up to 250 dollars of
      eligible expenses per month) increased the likelihood of any out-of-pocket
      spending for assistance (by 12%, p < .05), but it did not increase the amount of
      personal assistance expenditures among users (p = .94). Overall, the voucher
      benefits increased average annual expenditures by 10% (5,304 dollars for the
      voucher group vs 4,836 dollars for the control group). However, this effect did
      not reach statistical significance (p = .66). IMPLICATIONS: The voucher benefit
      provided a small incentive to use personal assistance for older Medicare
      beneficiaries with functional disabilities. Thus, if Medicare were to implement
      such a benefit, Medicare expenditures may increase. Further research is needed to
      determine if the increased personal assistance use leads to better health
      outcomes and whether it is associated with offset cost savings for Medicare
      covered services.

PMID- 16581883
TI  - Behavioral health services utilization among older adults identified within a
      state abuse hotline database.
AB  - PURPOSE: This study examined the extent to which older adults identified in a
      statewide abuse hotline registry utilized behavioral health services. This is
      important as mental health issues have been identified as a high priority for
      filling gaps in services for victims of mistreatment. DESIGN AND METHODS: We
      compared Medicaid and Medicare claims data for two groups of older adults: those
      using health services and identified within a statewide abuse hotline information
      system and those claimants not identified within the hotline database. RESULTS:
      Behavioral health service use was greater among those identified in the abuse
      hotline database. The penetration rate (percentage of service users out of all
      enrollees) for Medicaid behavioral health service claims was more than twice that
      of other service users, with costs of services about 30% greater. Analyses of
      Medicare data revealed that the penetration rate for those in the hotline data
      was almost 6 times greater at approximately twice the cost compared to other
      service users. IMPLICATIONS: The results provide evidence for previous
      assumptions that mistreated individuals experience a higher rate of behavioral
      health disorders. As mental health screening by adult protective services is
      rarely conducted, the results suggest the need to train investigators and other
      service providers to screen older adults for behavioral health and substance
      abuse issues as well as physical signs of abuse. Further research on the
      relationship of abuse to behavioral health might focus on collection of
      additional data involving more specific victim-related characteristics and
      comparisons of cases of mistreatment versus self-neglect.

PMID- 16581884
TI  - The extent and frequency of abuse in the lives of older women and their
      relationship with health outcomes.
AB  - PURPOSE: This study assessed the extent of different types of abuse, repeated and
      multiple abuse experiences among women aged 60 and older, and their effects on
      the women's self-reported health. DESIGN AND METHODS: A cross-sectional study of
      a clinical sample of 842 community-dwelling women aged 60 and older completed a
      telephone survey about type and frequency of abuse, self-reported health status
      and health conditions, and demographic characteristics. Bivariate and
      multivariate analyses were performed using SPSS 11.5 and STATA 7.0. RESULTS:
      Nearly half of the women had experienced at least one type of abuse-
      psychological/emotional, control, threat, physical, or sexual--since turning 55
      years old. Sizable proportions were victims of repeat abuse. Many women
      experienced multiple types of abuse and experienced abuse often. Abused older
      women were significantly more likely to report more health conditions than those
      who were not abused. Women who experienced psychological/emotional abuse--alone,
      repeatedly, or with other types of abuse--had significantly increased odds of
      reporting bone or joint problems, digestive problems, depression or anxiety,
      chronic pain, and high blood pressure or heart problems. IMPLICATIONS: It is
      important that health care and service providers acknowledge
      psychological/emotional, control, threat, physical, and sexual abuse against
      older women and understand their health implications. In addition, it is
      important for providers to be trained in both aging and domestic violence
      services and resources.

PMID- 16581885
TI  - Measuring staff turnover in nursing homes.
AB  - PURPOSE: In this study the levels of staff turnover reported in the nursing home
      literature (1990-2003) are reviewed, as well as the definitions of turnover used
      in these prior studies. With the use of primary data collected from 354
      facilities, the study addresses the various degrees of bias that result,
      depending on how staff turnover is defined in nursing homes. DESIGN AND METHODS:
      Data came from a survey mailed to administrators of 526 nursing homes during
      March 2003. Facilities were located in four states: Missouri, Texas, Connecticut,
      and New Jersey. Three hundred and fifty-four responses were received, giving a
      response rate of 67%. RESULTS: The 1-year turnover rates identified in these
      facilities were 119%, 89%, 87%, 57%, and 48%, for nurse aides, licensed practical
      nurses, registered nurses, administrators, and directors of nursing,
      respectively. However, findings show that the definition of turnover used could
      influence the relative difference between these reported rates by as much as 47%.
      IMPLICATIONS: As a result of measurement error, turnover rates may be
      misrepresented in prior studies. On the basis of the results of this
      investigation, several recommendations are made for future data-collection
      initiatives that will eliminate some of this measurement error.

PMID- 16581886
TI  - Interpersonal complexity: a cognitive component of person-centered care.
AB  - PURPOSE: This study concerns one component of the ability to provide person
      centered care: the cognitive skill of perceiving others in relatively complex
      terms. This study tested the effectiveness of a social motivation for increasing
      the number of psychological constructs used to describe an unfamiliar senior
      citizen. DESIGN AND METHODS: Forty-four certified nurse aide students
      participated. Students were mostly 30-year-old (M = 31) females (86%) with a high
      school education (72%). A quasi-experimental design was used. Early in training,
      participants completed the Role Category Questionnaire (RCQ), which measured
      their interpersonal cognitive complexity. On the basis of their RCQ scores,
      participants were matched and assigned to the experimental or control condition.
      Five weeks later, participants viewed a 15-min videotaped biography of an
      unfamiliar senior citizen--Mitch. Participants in both conditions were told they
      would be asked to describe Mitch as a person after watching the video. Only
      participants in the experimental condition were additionally asked to imagine
      that they would be having a personal conversation with him afterward. RESULTS: As
      hypothesized, participants in the experimental condition (M = 14.6) used more
      constructs to describe Mitch than did participants in the control condition (M =
      11.8): F(1, 41) = 4.03, p < .05. Participants' RCQ scores were significantly
      correlated with the complexity of their descriptions of Mitch. IMPLICATIONS: The
      findings suggest that new training materials should be created that include
      experienced certified nurse aides' modeling how biographical and personal
      information can be used in caregiving tasks to gain residents' cooperation.

PMID- 16581887
TI  - Team performance and risk-adjusted health outcomes in the Program of All
      Inclusive Care for the Elderly (PACE).
AB  - PURPOSE: The Program of All-Inclusive Care for the Elderly (PACE) is a community
      based program providing primary, acute, and long-term care to frail elderly
      individuals. A central component of the PACE model is the interdisciplinary care
      team, which includes both professionals and non-professionals. The purpose of
      this study was to examine the association between the team's overall performance
      and the risk-adjusted health outcomes of program enrollees. DESIGN AND METHODS:
      The study included interdisciplinary teams in 26 PACE programs and 3,401
      individuals enrolled in them. We combined information about individuals' health,
      functional, and mental status from DataPACE with an overall measure of team
      performance. We used multivariate regression techniques to test the hypothesis
      that better team performance is associated with better risk-adjusted health
      outcomes: survival and short-term (within 3 months of enrollment) and long-term
      (within 12 months of enrollment) improvements in functional status and in urinary
      incontinence. RESULTS: Team performance was significantly associated with better
      functional outcomes (both short and long term) and with better long-term urinary
      incontinence outcomes. There was no significant association with survival.
      IMPLICATIONS: This study provides empirical evidence for the relationship between
      team performance and patient outcomes in long-term care. It suggests that PACE
      programs can improve patient outcomes by improving the functioning of care teams.

PMID- 16581888
TI  - An empirical typology of residential care/assisted living based on a four-state
      study.
AB  - PURPOSE: Residential care/assisted living describes diverse facilities providing
      non-nursing home care to a heterogeneous group of primarily elderly residents.
      This article derives typologies of assisted living based on theoretically and
      practically grounded evidence. DESIGN AND METHODS: We obtained data from the
      Collaborative Studies of Long-Term Care, which examined 193 assisted living
      facilities in four states: Florida, Maryland, New Jersey, and North Carolina. By
      using mixture modeling, we derived typologies in five different ways, based on:
      structure; process; resident case-mix; structure and process; and structure,
      process, and resident case-mix. RESULTS: Although configurations of typologies
      varied as a function of criterion variables used, common themes emerged from
      different cluster solutions. A typology based on resident case-mix yielded a five
      cluster solution, whereas a typology based on structure, process, and resident
      case-mix resulted in six distinct clusters. Medicaid case-mix/psychiatric illness
      and high resident impairment were two clusters identified by both strategies.
      IMPLICATIONS: Because of the wide variation in structure, residents, and services
      within assisted living facilities, typologies such as those described here may be
      useful in clinical practice, research, and policy. To the extent that public
      payment defines its own cluster, the potential for inequities in care merits
      careful attention.

PMID- 16581889
TI  - Cross-sectional and longitudinal risk factors for falls, fear of falling, and
      falls efficacy in a cohort of middle-aged African Americans.
AB  - PURPOSE: The purpose of this study is to cross-sectionally and longitudinally
      identify risk factors for falls, fear of falling, and falls efficacy in late
      middle-aged African Americans. DESIGN AND METHODS: We performed in-home
      assessments on a probability sample of 998 African Americans and conducted two
      annual follow-up interviews. Multiple logistic regression modeled the
      associations with falls (any fall or injurious fall) during 2 years prior to the
      baseline interview, and baseline fear of falling and falls efficacy with 2-year
      prospective risks for falling and fear of falling. RESULTS: The most consistent
      association for all outcomes was depressive symptoms. Age was associated with
      increased risk of prior and prospective falls. Lower-body functional limitations
      were associated with prior falls, baseline fear of falling, and low falls
      efficacy, whereas low ability with one-leg stands prospectively predicted fear of
      falling. The greatest prospective risk for incident falls was having had a prior
      fall (odds ratio = 2.51), and the greatest prospective risk for fear of falling
      was having been afraid of falling at baseline (odds ratio = 8.14). IMPLICATIONS:
      Falls, fear of falling, and low falls efficacy are important issues for late
      middle-aged as well as older persons. Interventions should focus on younger
      adults and attend especially to lower-body function and depressive symptoms as
      well as building self-efficacy for safe exercise, dealing with falls risks, and
      managing falls themselves.

PMID- 16581890
TI  - Well-being in older Mexican American spouses.
AB  - PURPOSE: There is a strong connection between marriage and well-being, with
      evidence suggesting that the well-being of one spouse is closely correlated with
      that of the other. However, among older Mexican Americans, there is little
      information about this phenomenon. To address this, we explore two research
      questions: Does one spouse's well-being predict the other spouse's well-being?
      Are there gender differences in these effects? DESIGN AND METHODS: We assess
      information from 553 couples who participated in Wave 1 (1993-1994) of the
      Hispanic Established Populations for the Epidemiologic Studies of the Elderly.
      Using structural equation models, we examined three aspects of well-being among
      older Mexican American couples: depressive symptoms, life satisfaction, and self
      rated health. RESULTS: The findings revealed evidence of an association between
      the well-being of one spouse and that of the other. Specifically, the self-rated
      health of husbands and wives predicts that of their partners. However, there is
      evidence that husbands' depressive symptoms and life satisfaction influence
      wives' well-being, but not the reverse. IMPLICATIONS: The findings from this
      study are important because they add to the literature on the connection of well
      being among spouses, point to important gender differences, focus on an
      understudied minority group with unique cultural characteristics, and have
      implications for the examination of well-being within a marriage framework.

PMID- 16581891
TI  - Marital history and the burden of cardiovascular disease in midlife.
AB  - This study examines the effects of marital history on the burden of
      cardiovascular disease in midlife. With use of data from the 1992 Health and
      Retirement Study, a series of nested logistic regression models was used to
      estimate the association between marital history and the likelihood of
      cardiovascular disease. Results suggest that, in midlife, the continuously
      married and the never married are among the healthiest in cardiovascular
      outcomes. People with multiple marital losses are the most vulnerable group.
      People with multiple marital losses have a higher likelihood of cardiovascular
      disease and will need significant formal and informal care as they advance into
      old age.

PMID- 16581893
TI  - Findings from an elder abuse forensic center.
AB  - PURPOSE: The first Elder Abuse Forensic Center (EAFC) in the United States was
      instituted in 2003. People from a variety of disciplines, including Adult
      Protective Services social workers, law enforcement, the district attorney's
      office, a medical response team, public guardian deputies, ombudsmen, mental
      health services, a victim advocate, and a domestic violence expert work
      cooperatively on cases of elder and dependent-adult mistreatment. Researchers
      conducted an assessment of the EAFC's impact on the efficiency and effectiveness
      of the collaboration. DESIGN AND METHODS: Mixed quantitative and qualitative
      methods included statistical analysis of data from outcome surveys of EAFC
      collaborators and illustrative case studies developed from case files and
      structured interviews. RESULTS: Mean survey scores evaluating the efficiency and
      effectiveness of the collaboration were significantly better than neutral
      responses. Case studies show efficient and effective case management through
      cooperation of the collaborating agencies. Survey results clearly support
      perceptions exemplified in case studies. IMPLICATIONS: An EAFC enhances the
      efficiency and effectiveness of those who address elder abuse in one community,
      which in turn leads to improved outcomes. Continued analysis to identify
      strengths, weaknesses, and cost effectiveness of the EAFC model is ongoing.

PMID- 16581892
TI  - Just for Us: an academic medical center-community partnership to maintain the
      health of a frail low-income senior population.
AB  - PURPOSE: To promote health and maintain independence, Just for Us provides
      financially sustainable, in-home, integrated care to medically fragile, low
      income seniors and disabled adults living in subsidized housing. DESIGN AND
      METHODS: The program provides primary care, care management, and mental health
      services delivered in patient's homes by a multidisciplinary, multiagency team.
      RESULTS: After 2 years of operation, Just for Us is serving nearly 300
      individuals in 10 buildings. The program is demonstrating improvement in
      individual indices of health. Medicaid expenditures for enrollees are shifting
      from ambulances and hospital services to pharmacy, personal care, and outpatient
      visits. The program is not breaking even, but it is moving toward that goal. The
      program's success is based on a partnership involving an academic medical center,
      a community health center, county social and mental health agencies, and a city
      housing authority to coordinate and leverage services. IMPLICATIONS: Just for Us
      is becoming a financially sustainable way of creating a "system within a
      nonsystem" for low-income elderly persons in clustered housing.

PMID- 16581894
TI  - Feasibility of implementing the Strong for Life program in community settings.
AB  - PURPOSE: We describe the results of the dissemination of an efficacious, home
      based exercise program called Strong for Life as it was implemented in a
      nationwide, volunteer caregiving program called Faith in Action, including
      training of volunteers who implemented the program, recruitment of older adult
      participants, exercise adherence, and attitudes and perceptions of program staff
      and participants. DESIGN AND METHODS: Frail, homebound older adults (N = 105)
      were recruited from 10 Faith in Action sites to participate in the Strong for
      Life exercise program. Volunteer trainers (n = 103) were trained by physical
      therapists to assist the older adults with the program. Surveys were conducted
      with older adults, volunteer trainers, and Faith in Action sites at baseline and
      after the older adults had been engaged in the program for 4 months. RESULTS:
      Satisfaction with program components was very high: At follow-up, 100% of
      volunteers and 98.6% of older adults rated the program positively. Participants
      reported engaging in exercise on average 2.2 times per week, with 53% of the
      participants exercising at least 2 to 4 times per week. Participants also had
      significant improvements in the Short Form-20 social functioning scale. There
      were no serious adverse events reported. IMPLICATIONS: Dissemination of the
      Strong for Life program in a community setting using trained lay volunteers was
      feasible, acceptable, and safe. Existing volunteer caregiving organizations such
      as Faith in Action offer a feasible and safe means of disseminating late-life
      exercise programs to the frail older population.

PMID- 16581895
TI  - Markers of lung disease in exhaled breath: nitric oxide.
AB  - Management of airway inflammation requires proper monitoring and treatment to
      improve long-term outcomes. However, achieving this goal is difficult, as current
      methods have limitations. Although nitric oxide (NO) was first identified 200
      years ago, its physiological importance was not recognized until the early 1980s.
      Many studies have established the role of NO as an essential messenger molecule
      in body systems. In addition, studies have demonstrated a significant
      relationship between changes in exhaled NO levels and other markers of airway
      inflammation. The technique used to measure NO in exhaled breath is noninvasive,
      reproducible, sensitive, and easy to perform. Consequently, there is growing
      interest in the use of exhaled NO in the management of asthma and other pulmonary
      conditions. The purpose of this review is to promote a basic understanding of the
      physiologic actions of NO, measurement techniques, and ways that research
      findings might translate to future application in clinical practice.
      Specifically, the article will review the role of exhaled NO in regard to its
      historical background, mechanisms of action, measurement techniques, and
      implications for clinical practice and research.

PMID- 16581896
TI  - Heart rate variability and 24-hour minimum heart rate.
AB  - Heart rate variability (HRV) indices based on 24-hr electrocardiograph recordings
      have been used in clinical research studies to assess the aggregate activity of
      the autonomic nervous system. Although 24-hr HRV is generally considered
      noninvasive, use in research protocols typically involves considerable data
      collection and processing expenses and substantial participant burden. The
      purposes of this research methods evaluation were to describe the relationships
      between 24-hr minimum heart rate (HR) and several 24-hr time domain HRV indices
      (Ln SDNN, Ln SDANN, Ln SDNNIDX, Ln RMSSD, and Logit50) across several research
      data sets (normal women, normal men, children enrolled in a study of recurrent
      abdominal pain, women with irritable bowel syndrome, sudden cardiac arrest
      survivors, and heart failure patients) and to explore the possibility that 24-hr
      minimum HR might serve as a simpler alternative or adjunct to HRV measures in
      some situations. The correlations of global HRV measures (e.g., Ln SDNN, Ln
      SDANN) with 24-hr minimum HR were consistently larger (typical r approximately 
      .80) than with average HR (typical r approximately -.50). In repeated
      measurements, change in minimum HR was also correlated with change in general HRV
      (typical r approximately -.60). However, modest differentiation of minimum HR and
      HRV measures was noted in patients taking certain classes of cardiac medications
      (e.g., anti-arrhythmics, beta blockers). Twenty-four-hour minimum HR is
      correlated with general time domain HRV measures and might be useful as a simpler
      proxy, surrogate, or auxiliary variable in some clinical research applications,
      especially those in which participants are not receiving cardiac medications.

PMID- 16581897
TI  - Effects of endotracheal tube suctioning on arterial oxygen tension and heart rate
      variability.
AB  - The purpose of this study was to examine the autonomic mechanisms underlying
      changes in heart rate (HR) and systolic blood pressure (SBP) responses to
      endotracheal tube (ETT) suctioning and to compare the open versus closed methods
      of ETT suctioning on these measures and on arterial oxygen tension. Eighteen
      orally intubated participants, 33 to 82 years of age (M = 60 years), were
      randomized for the order of suctioning method. Arterial oxygen tension (PaO2) was
      measured before suctioning and 30 s and 5 min following suctioning. Beat-to-beat
      HR and arterial blood pressure data were collected for 10-min periods before and
      after suctioning. HR and SBP measures were analyzed before suctioning and 1 min
      and 5 min following suctioning. Although there were no significant effects of ETT
      suctioning on the autonomic mechanisms of HR modulation and no significant
      differences between the two methods of suctioning, ETT suctioning resulted in an
      increase in HR, SBP, and PaO2. However, there was a decrease in the
      parasympathetic nervous system indicator of HR variability (HRV) following open
      suctioning. All patients in this study maintained a PaO2 level 80 mm Hg, which
      may account for our lack of significant autonomic changes. This suggests that
      hyperoxygenation with 100% oxygen for a minimum of 1 min (or 20 breaths), as
      delivered by preoxygenation modes available on most microprocessor ventilators,
      should be the method of choice for all hyperoxygenation procedures to avoid a
      decrease in PaO2 following suctioning.

PMID- 16581898
TI  - The association of psychological factors, physical activity, neuropathy, and
      quality of life in type 2 diabetes.
AB  - The objective of this study was to determine the relationship of
      sociodemographics; diabetes-related factors, including diabetes-related
      microvascular complications; cardiac risk factors; and psychological factors with
      quality of life (QOL). Participants enrolled at three sites in the Detection of
      Ischemia in Asymptomatic Diabetics (DIAD) study were invited to participate in
      this ancillary study. Questionnaires assessing psychological factors were
      completed by participants, and the remainder of the data was obtained as part of
      the DIAD study. Many participants had elevated levels of anxiety (n = 91; 82%),
      depressive symptoms (n = 16; 14%), anger (n = 38; 34%), and hostility (n = 17;
      17%). Results of multivariate analyses conducted for each of the eight domains on
      the Medical Outcomes Study Short Form-36 and two Diabetes Quality of Life domains
      demonstrated that in the majority of models (42% to 68% of the variance
      explained), female sex, peripheral or autonomic neuropathy, physical inactivity,
      higher body mass index, and the presence of depressive symptoms and anxiety were
      associated with poorer QOL (p = .0001). These findings demonstrate that anxiety,
      depressive symptoms, and neuropathy are prevalent in older adults with type 2
      diabetes. In addition, potentially important correlations were demonstrated
      between psychological factors, neuropathy, body mass index, and physical
      inactivity.

PMID- 16581899
TI  - Cytosine arabinoside induces programmed endothelial cell death through the
      caspase-3 pathway.
AB  - The anti-cancer effects of cytosine arabinoside (ARA-C) are well known. However,
      effects on nonmalignant cells have not been elucidated and may be important to
      understanding treatment-related toxicity. The purpose of this study was to
      examine the effect of ARA-C on nondividing vascular endothelial cells. The
      objectives were to determine the effects of ARA-C on cell viability and to
      ascertain whether ARA-C caused apoptosis in cultured vascular endothelial cells
      and hydrocortisone blunted caspase-3-induced apoptosis. Endothelial cells were
      cultured until confluent and mitotically quiescent then exposed to ARA-C (10(
      7)to 10(-3) M) for 1 to 4 days. Some experiments involved cotreatment with
      hydrocortisone (10(-11),10(-10),10(-4), and 10(-3) M). Light microscopy and the
      colorimetric MTS assay were used to measure viability. Fluorescent annexin-V and
      DNA fragmentation assays were used to measure apoptosis, and a fluorescence-based
      enzymatic assay was used to measure caspase-3 activity, which is one pathway
      involved in the apoptosis cascade. Two-way ANOVA or the appropriate nonparametric
      test was used to determine statistical significance in studies of viability and
      apoptosis. Oneway ANOVA was used to determine statistical significance for
      caspase-3 activity. Viability was decreased with higher concentrations of ARA-C
      and increased days of treatment. The percentage of apoptotic cells increased with
      higher concentrations of ARA-C and increased days of treatment. ARA-C-treated
      samples showed DNA fragmentation, indicative of apoptosis. Caspase-3 activity
      increased after ARA-C addition; hydrocortisone blunted this increase. ARA-C
      caused apoptosis in nondividing endothelial cells in culture. Hydrocortisone may
      protect against ARA-C-induced apoptosis by reducing caspase-3 activity.

PMID- 16581900
TI  - The effect of pain on leukocyte cellular adhesion molecules.
AB  - The psychophysiological phenomenon of pain is of tremendous concern to nurses
      because of its potential to adversely affect the mental, emotional, and physical
      health of patients. Increasingly appreciated is the ability of pain to influence
      immune variables including enumerative and functional measures of leukocyte
      subsets. In this review, a theoretical model of the role of pain in producing
      positive changes in the expression of leukocyte cellular adhesion molecules is
      developed. The model is based on a conceptualization of pain as a perturbing
      influence on the complex web of neuroendocrine-immune relationships that regulate
      leukocyte migration. Findings from multiple lines of research are reviewed,
      including the neurophysiology and psychophysiology of pain, neuroendocrine and
      proinflammatory cytokine responses to painful stress, animal models linking pain
      to proinflammatory central immune activation, and pain-specific neurogenic
      inflammation. Relevant findings are synthesized to develop the physiological
      pathways from the perspective that pain may alter the balance of this
      multidirectional system in a proinflammatory direction. Clinical implications and
      suggestions for further research in the area of painful stress-related
      inflammation are offered.

PMID- 16581902
TI  - Exotic taxa less related to native species are more invasive.
AB  - Some species introduced into new geographical areas from their native ranges
      wreak ecological and economic havoc in their new environment. Although many
      studies have searched for either species or habitat characteristics that predict
      invasiveness of exotic species, the match between characteristics of the invader
      and those of members of the existing native community may be essential to
      understanding invasiveness. Here, we find that one metric, the phylogenetic
      relatedness of an invader to the native community, provides a predictive tool for
      invasiveness. Using a phylogenetic supertree of all grass species in California,
      we show that highly invasive grass species are, on average, significantly less
      related to native grasses than are introduced but noninvasive grasses. The match
      between the invader and the existing native community may explain why exotic pest
      species are not uniformly noxious in all novel habitats. Relatedness of invaders
      to the native biota may be one useful criterion for prioritizing management
      efforts of exotic species.

PMID- 16581903
TI  - Collegial decision making based on social amplification leads to optimal group
      formation.
AB  - Group-living animals are often faced with choosing between one or more
      alternative resource sites. A central question in such collective decision making
      includes determining which individuals induce the decision and when. This
      experimental and theoretical study of shelter selection by cockroach groups
      demonstrates that choices can emerge through nonlinear interaction dynamics
      between equal individuals without perfect knowledge or leadership. We identify a
      simple mechanism whereby a decision is taken on the move with limited information
      and signaling and without comparison of available opportunities. This mechanism
      leads to optimal mean benefit for group individuals. Our model points to a
      generic self-organized collective decision-making process independent of animal
      species.

PMID- 16581901
TI  - Chronic activation in presymptomatic amyotrophic lateral sclerosis (ALS) mice of
      a feedback loop involving Fas, Daxx, and FasL.
AB  - The reasons for the cellular specificity and slow progression of motoneuron
      diseases such as ALS are still poorly understood. We previously described a
      motoneuron-specific cell death pathway downstream of the Fas death receptor, in
      which synthesis of nitric oxide (NO) is an obligate step. Motoneurons from ALS
      model mice expressing mutant SOD1 showed increased susceptibility to exogenous NO
      as compared with controls. Here, we report a signaling mechanism whereby NO leads
      to death of mutant, but not control, motoneurons. Unexpectedly, exogenous NO
      triggers expression of Fas ligand (FasL) in cultured motoneurons. In mutant
      SOD1(G93A) and SOD1(G85R), but not in control motoneurons, this up-regulation
      results in activation of Fas, leading through Daxx to phosphorylation of p38 and
      further NO synthesis. This Fas/NO feedback amplification loop is required for
      motoneuron death in vitro. In vivo, mutant SOD1(G93A) and SOD1(G85R) mice show
      increased numbers of positive motoneurons and Daxx nuclear bodies weeks before
      disease onset. Moreover, FasL up-regulation is reduced in the presence of
      transgenic dominant-negative Daxx. We propose that chronic low-level activation
      of the Fas/NO feedback loop may underlie the motoneuron loss that characterizes
      familial ALS and may help to explain its slowly progressive nature.

PMID- 16581906
TI  - Symmetry-, time-, and temperature-dependent strength of carbon nanotubes.
AB  - Although the strength of carbon nanotubes has been of great interest, their ideal
      value has remained elusive both experimentally and theoretically. Here, we
      present a comprehensive analysis of underlying atomic mechanisms and evaluate the
      yield strain for arbitrary nanotubes at realistic conditions. For this purpose,
      we combine detailed quantum mechanical computations of failure nucleation and
      transition-state barriers with the probabilistic approach of the rate theory. The
      numerical results are then summarized in a concise set of equations for the
      breaking strain. We reveal a competition between two alternative routes of
      brittle bond breaking and plastic relaxation, determine the domains of their
      dominance, and map the nanotube strength as a function of chiral symmetry,
      tensile test time, and temperature.

PMID- 16581905
TI  - Aurora A, mitotic entry, and spindle bipolarity.
AB  - The kinase Aurora-A (Aur-A), which is enriched at centrosomes, is required for
      centrosome maturation and accurate chromosome segregation, and recent work
      implicates centrosomes as sites where the earliest activation of cyclin B1-cdc2
      occurs. Here, we have used Xenopus egg extracts to investigate Aur-A's
      contribution to cell cycle progression and spindle morphology in the presence or
      absence of centrosomes. We find that addition of active Aur-A accelerates cdc2
      activation and mitotic entry. Depletion of endogenous Aur-A or addition of
      inactive Aur-A, which lead to monopolar spindles, delays but does not block
      mitotic entry. These effects on timing and spindle structure do not require the
      presence of centrosomes or chromosomes. The catalytic domain alone of Aur-A is
      sufficient to restore spindle bipolarity; additional N-terminal sequences
      function in mitotic timing.

PMID- 16581904
TI  - Presence/absence polymorphism for alternative pathogenicity islands in
      Pseudomonas viridiflava, a pathogen of Arabidopsis.
AB  - The contribution of arms race dynamics to plant-pathogen coevolution has been
      called into question by the presence of balanced polymorphisms in resistance
      genes of Arabidopsis thaliana, but less is known about the pathogen side of the
      interaction. Here we investigate structural polymorphism in pathogenicity islands
      (PAIs) in Pseudomonas viridiflava, a prevalent bacterial pathogen of A. thaliana.
      PAIs encode the type III secretion system along with its effectors and are
      essential for pathogen recognition in plants. P. viridiflava harbors two
      structurally distinct and highly diverged PAI paralogs (T- and S-PAI) that are
      integrated in different chromosome locations in the P. viridiflava genome. Both
      PAIs are segregating as presence/absence polymorphisms such that only one PAI ([T
      PAI, nablaS-PAI] and [nablaT-PAI, S-PAI]) is present in any individual cell. A
      worldwide population survey identified no isolate with neither or both PAI. T-PAI
      and S-PAI genotypes exhibit virulence differences and a host-specificity
      tradeoff. Orthologs of each PAI can be found in conserved syntenic locations in
      other Pseudomonas species, indicating vertical phylogenetic transmission in this
      genus. Molecular evolutionary analysis of PAI sequences also argues against
      "recent" horizontal transfer. Spikes in nucleotide divergence in flanking regions
      of PAI and nabla-PAI alleles suggest that the dual PAI polymorphism has been
      maintained in this species under some form of balancing selection. Virulence
      differences and host specificities are hypothesized to be responsible for the
      maintenance of the dual PAI system in this bacterial pathogen.

PMID- 16581907
TI  - Reactivation by exon shuffling of a conserved HLA-DR3-like pseudogene segment in
      a New World primate species.
AB  - The common marmoset (Callithrix jacchus), a New World monkey species with a
      limited MHC class II repertoire, is highly susceptible to certain bacterial
      infections. Genomic analysis of exon 2 sequences documented the existence of only
      one DRB region configuration harboring three loci. Two of these loci display
      moderate levels of allelic polymorphism, whereas the -DRB*W12 gene appears to be
      monomorphic. This study shows that only the Caja-DRB*W16 and -DRB*W12 loci
      produce functional transcripts. The Caja-DRB1*03 locus is occupied by a
      pseudogene, given that most of the transcripts, if detected at all, show
      imperfections and are present at low levels. Moreover, two hybrid transcripts
      were identified that feature the evolutionarily conserved peptide-binding motif
      characteristic for the Caja-DRB1*03 gene. Thus, the severely reduced MHC class II
      repertoire in common marmosets has been expanded by reactivation of a pseudogene
      segment as a result of exon shuffling.

PMID- 16581908
TI  - Severe urinary concentrating defect in renal collecting duct-selective AQP2
      conditional-knockout mice.
AB  - Aquaporin-2 (AQP2) is the predominant vasopressin-regulated water channel in
      kidney connecting tubule (CNT) and collecting duct (CD) and is essential for
      renal regulation of body water balance. However, the relative role of AQP2 to
      urinary concentration in the CNT and CD segments is unknown. To examine this
      directly, transgenic mice expressing AQP2 selectively in CNT but lacking AQP2
      expression in CD (AQP2-CD-KO) and mice lacking AQP2 globally (AQP2-total-KO) were
      generated by exploiting the Cre/loxP technology. LoxP sites were inserted into
      AQP2 introns 2 and 3, and transgenic mice were bred with strains expressing Cre
      recombinase under the control of CD-specific Hoxb7- or global EIIa promoter. Mice
      lacking AQP2 globally died postnatally (days 5-12). AQP2-CD-KO mice were viable
      to adulthood and showed decreased body weight, 10-fold increased urine production
      (0.96 +/- 0.11 vs. 0.10 +/- 0.01 ml/g of body weight), and decreased urinary
      osmolality (170 +/- 19 vs. 1,630 +/- 135 milliosmoles/kg of H(2)O).
      Immunohistochemical staining of AQP2-CD-KO kidneys (n = 12) revealed sustained,
      strong AQP2 expression in CNT cells, whereas >95% of CD principal cells were
      completely AQP2-negative. Water deprivation for 3 hours caused only marginal
      decreased urine output (87 +/- 7% of levels when mice had free water access; P =
      0.04) with no change in urine osmolality, revealing an absence of compensatory
      mechanisms. These results demonstrate that AQP2 in CNT is sufficient for
      postnatal survival and that AQP2 in CD is essential for regulation of body water
      balance and cannot be compensated for by other mechanisms.

PMID- 16581909
TI  - Comparative promoter analysis allows de novo identification of specialized cell
      junction-associated proteins.
AB  - Shared transcription factor binding sites that are conserved in distance and
      orientation help control the expression of gene products that act together in the
      same biological context. New bioinformatics approaches allow the rapid
      characterization of shared promoter structures and can be used to find novel
      interacting molecules. Here, these principles are demonstrated by using molecules
      linked to the unique functional unit of the glomerular slit diaphragm. An
      evolutionarily conserved promoter model was generated by comparative genomics in
      the proximal promoter regions of the slit diaphragm-associated molecule nephrin.
      Phylogenetic promoter fingerprints of known elements of the slit diaphragm
      complex identified the nephrin model in the promoter region of zonula occludens-1
      (ZO-1). Genome-wide scans using this promoter model effectively predicted a
      previously unrecognized slit diaphragm molecule, cadherin-5. Nephrin, ZO-1, and
      cadherin-5 mRNA showed stringent coexpression across a diverse set of human
      glomerular diseases. Comparative promoter analysis can identify regulatory
      pathways at work in tissue homeostasis and disease processes.

PMID- 16581911
TI  - Transcriptional and posttranscriptional regulation of transcription factor
      expression in Arabidopsis roots.
AB  - Understanding how the expression of transcription factor (TF) genes is modulated
      is essential for reconstructing gene regulatory networks. There is increasing
      evidence that sequences other than upstream noncoding can contribute to
      modulating gene expression, but how frequently they do so remains unclear. Here,
      we investigated the regulation of TFs expressed in a tissue-enriched manner in
      Arabidopsis roots. For 61 TFs, we created GFP reporter constructs driven by each
      TF's upstream noncoding sequence (including the 5'UTR) fused to the GFP reporter
      gene alone or together with the TF's coding sequence. We compared the visually
      detectable GFP patterns with endogenous mRNA expression patterns, as defined by a
      genome-wide microarray root expression map. An automated image analysis method
      for quantifying GFP signals in different tissues was developed and used to
      validate our visual comparison method. From these combined analyses, we found
      that (i) the upstream noncoding sequence was sufficient to recapitulate the mRNA
      expression pattern for 80% (35/44) of the TFs, and (ii) 25% of the TFs undergo
      posttranscriptional regulation via microRNA-mediated mRNA degradation (2/24) or
      via intercellular protein movement (6/24). The results suggest that, for
      Arabidopsis TFs, upstream noncoding sequences are major contributors to mRNA
      expression pattern establishment, but modulation of transcription factor protein
      expression pattern after transcription is relatively frequent. This study
      provides a systematic overview of regulation of TF expression at a cellular
      level.

PMID- 16581910
TI  - Severe acute respiratory syndrome coronavirus papain-like protease: structure of
      a viral deubiquitinating enzyme.
AB  - Replication of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV)
      requires proteolytic processing of the replicase polyprotein by two viral
      cysteine proteases, a chymotrypsin-like protease (3CLpro) and a papain-like
      protease (PLpro). These proteases are important targets for development of
      antiviral drugs that would inhibit viral replication and reduce mortality
      associated with outbreaks of SARS-CoV. In this work, we describe the 1.85-A
      crystal structure of the catalytic core of SARS-CoV PLpro and show that the
      overall architecture adopts a fold closely resembling that of known
      deubiquitinating enzymes. Key features, however, distinguish PLpro from
      characterized deubiquitinating enzymes, including an intact zinc-binding motif,
      an unobstructed catalytically competent active site, and the presence of an
      intriguing, ubiquitin-like N-terminal domain. To gain insight into the active
      site recognition of the C-terminal tail of ubiquitin and the related LXGG motif,
      we propose a model of PLpro in complex with ubiquitin-aldehyde that reveals well
      defined sites within the catalytic cleft that help to account for strict
      substrate-recognition motifs.

PMID- 16581912
TI  - A chemokine-binding domain in the tumor necrosis factor receptor from variola
      (smallpox) virus.
AB  - Variola virus (VaV) is the causative agent of smallpox, one of the most
      devastating diseases encountered by man, that was eradicated in 1980. The
      deliberate release of VaV would have catastrophic consequences on global public
      health. However, the mechanisms that contribute to smallpox pathogenesis are
      poorly understood at the molecular level. The ability of viruses to evade the
      host defense mechanisms is an important determinant of viral pathogenesis. Here
      we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by
      VaV functions not only as a soluble decoy TNFR but also as a highly specific
      binding protein for several chemokines that mediate recruitment of immune cells
      to mucosal surfaces and the skin, sites of virus entry and viral replication at
      late stages of smallpox. CrmB binds chemokines through its C-terminal domain,
      which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor
      (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active
      SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins
      encoded by orthopoxviruses. These findings identify a previously undescribed
      chemokine-binding and inhibitory domain unrelated to host chemokine receptors and
      a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.

PMID- 16581913
TI  - Protein stability promotes evolvability.
AB  - The biophysical properties that enable proteins to so readily evolve to perform
      diverse biochemical tasks are largely unknown. Here, we show that a protein's
      capacity to evolve is enhanced by the mutational robustness conferred by extra
      stability. We use simulations with model lattice proteins to demonstrate how
      extra stability increases evolvability by allowing a protein to accept a wider
      range of beneficial mutations while still folding to its native structure. We
      confirm this view experimentally by mutating marginally stable and thermostable
      variants of cytochrome P450 BM3. Mutants of the stabilized parent were more
      likely to exhibit new or improved functions. Only the stabilized P450 parent
      could tolerate the highly destabilizing mutations needed to confer novel
      activities such as hydroxylating the antiinflammatory drug naproxen. Our work
      establishes a crucial link between protein stability and evolution. We show that
      we can exploit this link to discover protein functions, and we suggest how
      natural evolution might do the same.

PMID- 16581915
TI  - Artesunate and artemether are effective fasciolicides in the rat model and in
      vitro.
AB  - OBJECTIVES: To study the fasciocidal properties of artesunate and artemether in
      the rat model and in vitro. METHODS: Adult Fasciola hepatica were exposed in
      vitro to 1, 10 and 100 microg/mL of artesunate, artemether and dihydroartemisinin
      for 72 h. Female Wistar rats were administered a single oral dose of artesunate
      and artemether (100-400 mg/kg) commencing 3 or 10-14 weeks post-infection and
      worm burden reductions were assessed against infected but untreated control rats.
      F. hepatica were also observed by scanning electron microscopy (SEM) after
      recovery from bile ducts of rats given a single oral dose of 200 mg/kg artesunate
      24 and 72 h post-treatment. RESULTS: F. hepatica exposed for 72 h to 10 microg/mL
      of artesunate, artemether and dihydroartemisinin in vitro showed poor mobility,
      swelling of the worm body, roughness, damage of the tegument and blebbing.
      Exposure to drug concentrations of 100 microg/mL resulted in the death of all F.
      hepatica by 72 h. One hundred per cent worm burden reductions were achieved in
      rats infected with adult F. hepatica after treatment with artesunate and
      artemether at 400 and 200 mg/kg, respectively. Administration of artesunate and
      artemether at a dose of 200 mg/kg to rats harbouring juvenile F. hepatica
      resulted in worm burden reductions of 46% and 82%, respectively. F. hepatica
      recovered from rats' bile ducts 24 h after administration of 200 mg/kg artesunate
      showed normal activity and SEM observations revealed that there was no visible
      damage. Seventy-two hours post-treatment F. hepatica displayed very poor mobility
      and there was focal swelling of the tegument and spines. CONCLUSIONS: Artesunate
      and artemether exhibit promising fasciocidal activities, with the latter showing
      better tolerability by the hosts.

PMID- 16581914
TI  - Ethanol potently and competitively inhibits binding of the alcohol antagonist
      Ro15-4513 to alpha4/6beta3delta GABAA receptors.
AB  - Although GABA(A) receptors have long been implicated in mediating ethanol (EtOH)
      actions, receptors containing the "nonsynaptic" delta subunit only recently have
      been shown to be uniquely sensitive to EtOH. Here, we show that delta subunit
      containing receptors bind the imidazo-benzodiazepines (BZs) flumazenil and Ro15
      4513 with high affinity (K(d) < 10 nM), contrary to the widely held belief that
      these receptors are insensitive to BZs. In immunopurified native cerebellar and
      recombinant delta subunit-containing receptors, binding of the alcohol antagonist
      [(3)H]Ro15-4513 is inhibited by low concentrations of EtOH (K(i) approximately 8
      mM). Also, Ro15-4513 binding is inhibited by BZ-site ligands that have been shown
      to reverse the behavioral alcohol antagonism of Ro15-4513 (i.e., flumazenil, beta
      carbolinecarboxylate ethyl ester (beta-CCE), and N-methyl-beta-carboline-3
      carboxamide (FG7142), but not including any classical BZ agonists like diazepam).
      Experiments that were designed to distinguish between a competitive and
      allosteric mechanism suggest that EtOH and Ro15-4513 occupy a mutually exclusive
      binding site. The fact that only Ro15-4513, but not flumazenil, can inhibit the
      EtOH effect, and that Ro15-4513 differs from flumazenil by only a single group in
      the molecule (an azido group at the C7 position of the BZ ring) suggest that this
      azido group in Ro15-4513 might be the area that overlaps with the alcohol-binding
      site. Our findings, combined with previous observations that Ro15-4513 is a
      behavioral alcohol antagonist, suggest that many of the behavioral effects of
      EtOH at relevant physiological concentrations are mediated by EtOH/Ro15-4513
      sensitive GABA(A) receptors.

PMID- 16581916
TI  - Effect of human vicinity on antimicrobial resistance and integrons in animal
      faecal Escherichia coli.
AB  - OBJECTIVES: To determine the level of antimicrobial resistance and the occurrence
      of class 1, 2 and 3 integrons in faecal Escherichia coli from several animal
      populations variously exposed to human contact. METHODS: A collection of 341
      faecal E. coli isolates was constituted from several animal populations subject
      to various degrees of exposure to humans: 18 animals never exposed to humans
      (living in the Antarctic or Gabon), 71 wild animals living in a low human density
      area (mountainous region of the Pyrenees, France), 61 wild animals living in a
      higher human density area (Fontainebleau forest near Paris, France), and 128
      extensively reared farm animals and 42 pet dogs, both living in the Pyrenees.
      Resistance to antimicrobial agents was determined by the method of disc diffusion
      and quantified using the resistance score of BE Murray, JJ Mathewson, HL DuPont,
      CD Ericsson and RR Reves (Antimicrobial Agents and Chemotherapy 1990; 34: 515
      18). Integrons were characterized by triplex real-time PCR and sequencing. The
      absence of epidemiologic clones was confirmed by PCR-based methods. RESULTS: A
      gradient of resistance ranging from absence to high prevalence (resistance score
      of 18.7%) and a gradual increase in the prevalence of class 1 integrons (from 0%
      to 16%), both correlated with the increase in exposure to humans, were observed.
      In wild animals with little contact with humans, resistance, when present, was
      not mediated by integrons. CONCLUSIONS: Our findings firmly establish that the
      current prevalence of antimicrobial resistance found in animal faecal bacteria,
      as well as the prevalence of integrons, is clearly anthropogenic. The presence of
      integrons may constitute an adaptive process to environments whose antimicrobial
      pressure exceeds a certain threshold.

PMID- 16581917
TI  - Risk factors for specific methicillin-resistant Staphylococcus aureus clones in a
      Korean hospital.
AB  - OBJECTIVES: To analyse the risk factors for nosocomial methicillin-resistant
      Staphylococcus aureus (MRSA) infections caused by different clonal types.
      METHODS: A total of 134 non-duplicate nosocomial MRSA isolates were analysed for
      clonal types by molecular typing techniques. The medical records of 90 patients
      who had documented MRSA infection were evaluated retrospectively. RESULTS: Two
      predominant MRSA clones of sequence types (STs) ST239 (n = 75) and ST5 (n = 39)
      accounted for 85% of the isolates. Management of patients in the departments of
      orthopaedic surgery, neurosurgery and plastic surgery was identified as a risk
      factor for infection with MRSA of ST239, while the presence of intravascular
      catheters was a risk factor for infection with ST5. Pulmonary infection was
      significantly higher in the patients infected with ST239 strains than in the
      patients infected with ST5 strains (P < 0.05). The overall mean duration of
      antimicrobial therapy for the patients with ST239 infection was significantly
      more than that for the patients with ST5 infection (P < 0.05). CONCLUSIONS: ST239
      and ST5 were the predominant MRSA clones in the study hospital. Risk factors were
      significantly different between ST239 and ST5 strains. The results of this study
      will be of use in designing larger prospective epidemiological studies for MRSA
      infection based on clonal types.

PMID- 16581918
TI  - Dosimetric issues in radiation protection of radiotherapy patients.
AB  - As life expectancy increases, thanks to improving general medical practices,
      cancer treatments for the ageing population become evermore necessary. Radiation
      therapy is increasingly a treatment of choice, promoted by continuing
      improvements in dose delivery technologies. Some techniques, collectively
      referred to as intensity-modulated radiation therapy, are encountering widespread
      acceptance and implementation, promoted by reports of superior tumour control and
      reduced toxicity. However, these new techniques pose new challenges in terms of
      radiation protection of patients, as they cause a more extensive low-dose
      exposure of normal tissues compared with conventional radiation therapy. The
      related dosimetric challenges and the methods available to tackle them are
      reviewed in this paper, which also emphasises the need for standard radiation
      protection dosimetry procedures so that information may be consistently gathered
      for a comparative evaluation of the different treatment modalities.

PMID- 16581919
TI  - Radiation dose from cigarette tobacco.
AB  - The radioactivity in tobacco leaves collected from 15 different regions of Greece
      before cigarette production was studied in order to estimate the effective dose
      from cigarette tobacco due to the naturally occurring primordial radionuclides,
      such as (226)Ra and (210)Pb of the uranium series and (228)Ra of the thorium
      series and or man-made radionuclides, such as (137)Cs of Chernobyl origin. Gamma
      ray spectrometry was applied using Ge planar and coaxial type detectors of high
      resolution and high efficiency. It was concluded that the annual effective dose
      due to inhalation for adults (smokers) for (226)Ra varied from 42.5 to 178.6
      microSv y(-1) (average 79.7 microSv y(-1)), while for (228)Ra from 19.3 to 116.0
      microSv y(-1) (average 67.1 microSv y(-1)) and for (210)Pb from 47.0 to 134.9
      microSv y(-1) (average 104.7 microSv y(-1)), that is the same order of magnitude
      for each radionuclide. The sum of the effective doses of the three natural
      radionuclides varied from 151.9 to 401.3 microSv y(-1) (average 251.5 microSv y(
      1)). The annual effective dose from (137)Cs of Chernobyl origin was three orders
      of magnitude lower as it varied from 70.4 to 410.4 nSv y(-1) (average 199.3 nSv
      y(-1)).

PMID- 16581920
TI  - Aircraft crew radiation workplaces: comparison of measured and calculated ambient
      dose equivalent rate data using the EURADOS in-flight radiation data base.
AB  - In May 2000, the chairman of the European Radiation Dosimetry Group (EURADOS)
      invited a number of experts with experience of cosmic radiation dosimetry to form
      a working group (WG 5) on aircraft crew dosimetry. Three observers from the
      Article 31 Group of Experts as well as one observer from the Joint Aviation
      Authorities (JAA) were also appointed. The European Commission funded the
      meetings. Full meetings were organised in January 2001 and in November 2001. An
      editorial group, who are the authors of this publication, started late in 2002 to
      finalise a draft report, which was submitted to the Article 31 Group of Experts
      in June 2003. The methods and data reported are the product of the work of 26
      research institutes from the EU, USA and Canada. Some of the work was supported
      by contracts with the European Commission, Directorate General XII, Science,
      Research and Development. A first overview of the EC report was published late in
      2004. In this publication we focus on a comparison of measured and calculated
      ambient dose rate data using the EURADOS In-Flight Data Base. The evaluation of
      results obtained by different methods and groups, and comparison of measurement
      results and the results of calculations were performed in terms of the
      operational quantity ambient dose equivalent, H*(10). Aspects of measurement
      uncertainty are reported also. The paper discusses the estimation of annual doses
      for given flight hours and gives an outline of further research needed in the
      field of aircraft crew dosimetry, such as the influence of solar particle events.

PMID- 16581921
TI  - The use of extremity dosemeters in a hospital environment.
AB  - A general overview is given on the use of extremity dosemeters, their
      calibration, the units and phantoms to be used. One of the major applications of
      extremity dosemeters is to monitor the personnel in a hospital environment. In
      nuclear medicine, brachytherapy and interventional radiology (IR) skin doses to
      hands and legs can be substantial. Here, we report on two studies that are
      presently being undertaken in Belgium. The first one tries to map the dose
      distribution on the hands, in function of the manipulation in nuclear medicine.
      Some preliminary results are also given from a nationwide survey study for
      patient and personnel doses during IR and cardiology. The radiologists' hands,
      legs and forehead are monitored during a whole range of procedures in different
      hospitals.

PMID- 16581922
TI  - Individual monitoring for internal exposures in Europe: conclusions of an EURADOS
      action.
AB  - Once the EC Directive 96/29 has been implemented into national regulation across
      Europe, the coordination of dosimetry laboratories for the monitoring of
      occupational exposures becomes the principal aim to achieve. Within this
      framework the European Radiation Dosimetry Group, EURADOS, carried out an Action
      on 'Harmonisation of Individual Monitoring' (2000-2004) to promote coordination
      in the field of individual monitoring of occupational exposures throughout
      Europe. With reference to internal exposures, the main aims were the completion
      of a catalogue of internal dosimetry services and an inventory of methods and
      techniques used for individual monitoring at European internal dosimetry
      facilities. At the end of this EURADOS Action, a report was published in
      Radiation Protection Dosimetry in 2004. The information collected related to
      various topics: the equipments used for the measurement of internal exposures,
      calibration and sensitivity data, the methods applied for the assessment of
      internal doses, Quality Control procedures, Quality Assurance Programmes in the
      facilities and legal requirements. The information to be presented here will give
      a general overview of the actual status of individual monitoring for internal
      exposures in Europe.

PMID- 16581923
TI  - Aspects of harmonisation of individual monitoring for external radiation in
      Europe: conclusions of a EURADOS action.
AB  - Following the publication of the EU Council Directive 96/29, EURADOS coordinated
      two working groups (WGs) for promoting the process of harmonisation on individual
      monitoring of occupationally exposed persons in Europe. An overview of the major
      findings of the second WG is presented. Information on the technical and quality
      standards and on the accreditation and approval procedures has been compiled. The
      catalogue of dosimetric services has been updated and extended. An overview of
      national regulations and standards for protection from radon and other natural
      sources in workplaces has been made, attempting to combine the results from
      individual monitoring for external, internal and workplace monitoring. A first
      status description of the active personal dosemeters, including legislative and
      technical information, and their implementation has been made. The importance of
      practical factors on the uncertainty in the dose measurement has been estimated.
      Even if a big progress has been made towards harmonisation, there is still work
      to be done.

PMID- 16581924
TI  - Thermoluminescence of terbium sensitised by samarium in CaF2.
AB  - Thermoluminescence (TL) in sintered CaF2 doped with Tb4O7 has been studied for UV
      and X-ray irradiation. Three TL glow peaks for the Tb4O7 doped sample appeared in
      the temperature regions of about (1) 347-353 K, (2) 378-383 K and (3) 453-458 K,
      when heated at a rate of 20 K min(-1) after UV or X-ray irradiation at room
      temperature. It has been found that the 378 K peak intensity of the samples co
      doped with Tb4O7 and Sm2O3 became stronger when compared with those doped with
      only terbium or samarium ions, and the TL peaks of (1) 347-353 K and (3) 453-458
      K were not observed. The intensity of the 378 K peak of the co-doped sample was
      12.9 times that of the sample doped only with Tb4O7. From the TL spectra and the
      excitation and emission spectra of photoluminescence for the CaF2 doped
      activators, it is concluded that the TL of Tb3+ ions is sensitised by the
      existence of Sm3+ ions. The 378 K TL peak may also be suitable for UV radiation
      dosimetry.

PMID- 16581925
TI  - Kerma rate effects on thermoluminescent response of CVD diamond.
AB  - The thermoluminescence (TL) response of chemical vapour deposition diamond is
      studied after X-irradiation (45 kV) at room temperature for various air kerma
      rates ranging from 0.7 to 100 Gy.min(-1). For a given air kerma, the TL signal as
      a function of air kerma rate exhibits large variations and is higher for low air
      kerma rates than for higher ones. In order to explain these results, the simplest
      energy-level scheme has been considered, that is, with only one electron trap and
      one recombination centre. Kinetic equations are numerically solved. Calculations
      are made for various electron-hole generation rates and show that the trap
      filling as a function of electron-hole generation rate follows, actually, the
      same evolution as the one of experimental TL response. The kerma rate effect on
      TL response is explained by the competitivity between the recombination and the
      trapping processes during irradiation.

PMID- 16581926
TI  - Theoretical modelling of experimental diagnostic procedures employed during pre
      dose dosimetry of quartz.
AB  - The pre-dose technique in thermoluminescence (TL) is used for dating
      archaeological ceramics and for accident dosimetry. During routine applications
      of this technique, the sensitisation of the quartz samples is measured as a
      function of the annealing temperature, yielding the so-called thermal activation
      characteristic (TAC). The measurement of multiple TACs and the study of the
      effect of UV-radiation on the TL sensitivity of quartz are important analytical
      and diagnostic tools. In this paper, it is shown that a modified Zimmerman model
      for quartz can successfully model the experimental steps undertaken during a
      measurement of multiple TACs.

PMID- 16581927
TI  - Defects creation under UV irradiation of PbWO4 crystals.
AB  - A systematic study of photothermally stimulated defects creation processes is
      carried out by the thermally stimulated luminescence (TSL) method for a large
      number of undoped and doped PbWO4 crystals under irradiation at 80-180 K in the
      3.4-4.3 eV energy range. The activation energy Ea for the regular exciton state
      disintegration is found to be approximately 0.1 eV. For defect-related states
      disintegration, Ea varies in the crystals studied from 0.03 to 0.36 eV. The
      origin of the defect-related states is discussed. The conclusion is made that not
      only a release of charge carriers but also charge transfer processes take place
      under UV irradiation of PbWO4 crystals.

PMID- 16581928
TI  - Space dosimetry with the application of a 3D silicon detector telescope: response
      function and inverse algorithm.
AB  - One of the many risks of long-duration space flights is the excessive exposure to
      cosmic radiation, which has great importance particularly during solar flares and
      higher sun activity. Monitoring of the cosmic radiation on board space vehicles
      is carried out on the basis of wide international co-operation. Since space
      radiation consists mainly of charged heavy particles (protons, alpha and heavier
      particles), the equivalent dose differs significantly from the absorbed dose. A
      radiation weighting factor (w(R)) is used to convert absorbed dose (Gy) to
      equivalent dose (Sv). w(R) is a function of the linear energy transfer of the
      radiation. Recently used equipment is suitable for measuring certain radiation
      field parameters changing in space and over time, so a combination of different
      measurements and calculations is required to characterise the radiation field in
      terms of dose equivalent. The objectives of this project are to develop and
      manufacture a three-axis silicon detector telescope, called Tritel, and to
      develop software for data evaluation of the measured energy deposition spectra.
      The device will be able to determine absorbed dose and dose equivalent of the
      space radiation.

PMID- 16581929
TI  - Thermoluminescent detectors applied in individual monitoring of radiation workers
      in Europe--a review based on the EURADOS questionnaire.
AB  - Among the activities of EURADOS Working Group 2 formed by experts from several
      European countries is the harmonisation of individual monitoring as part of
      radiation protection of occupationally exposed persons. Here, we provide
      information about thermoluminescent detectors (TLDs) applied by the European
      dosimetric services and the dosimetric characteristics of dosemeters in which
      these detectors are applied. Among 91 services from 29 countries which responded
      to the EURADOS questionnaire, 61 apply dosemeters with TLDs for the determination
      of personal dose equivalent H(p)(10) for photons and beta radiation, and 16
      services use TLDs for neutron albedo dosemeters. Those most frequently used are
      standard lithium fluoride TLDs (mainly TLD-100, TLD-700, Polish MTS-N and MTS-7,
      Russian DTG-4), high-sensitive lithium fluoride (GR-200, MCP-N) and lithium
      borate TLDs. Some services use calcium sulphate and calcium fluoride detectors.
      For neutron dosimetry, most services apply pairs of LiF:Mg,Ti TLDs with (6)Li and
      (7)Li. The characteristics (energy response) of individual dosemeters are mainly
      related to the energy response of the detectors and filters applied. The
      construction of filters in dosemeters applied for measurements of H(p)(10) and
      their energy response are also reviewed.

PMID- 16581930
TI  - LiF:Mg,Cu,P glow curve shape dependence on heating rate.
AB  - The glow curve shape of LiF:Mg,Cu,P (MCP) material is studied in this research.
      The study is focused on the effects of the heating rate on the dosimetric peaks.
      Different configurations of dosemeters (chips, cards and powder) are studied. The
      shifting of the dominant dosimetric peak is observed and analysed. The curves are
      deconvoluted using the new Harshaw Glow Curve Analyser (GCA) program. Results of
      the study are presented, as well as possible explanations as to the observed
      effects.

PMID- 16581931
TI  - The dose-response of Harshaw TLD-700H.
AB  - Harshaw TLD-700H (7LiF:Mg,Cu,P) was previously characterised for low- to high
      dose ranges from 1 microGy to 20 Gy. This paper describes the studies and results
      of dose-response and linearity at much higher doses. TLD-700H is a near perfect
      dosimetric material with near tissue equivalence, flat energy response, and the
      ability to measure beta, gamma and X rays. These new results extend the
      applicability of Harshaw TLD-700H into more dosimetric measurement environments.
      The simple glow curve structure provides insignificant fade, eliminating special
      oven preparation methods experienced by other materials. The work presented in
      this paper quantifies the performance of Harshaw TLD-700H in extended ranges.

PMID- 16581932
TI  - Development of an emergency department work score to predict ambulance diversion.
AB  - OBJECTIVES: The authors sought to develop and validate an emergency department
      (ED) work score that could be used in real time to quantify crowding and staff
      workload in an ED. This work score could be used by public health officials to
      direct ambulance traffic based on an objective measure of ED status and to track
      ED conditions over time. In addition, the authors sought to determine which
      portion of ED care was most responsible for crowding. METHODS: The setting was a
      tertiary teaching hospital with an emergency medicine residency. A number of ED
      parameters were measured throughout 2003 and then matched to times that an ED was
      on diversion status. Odd months of the year were used to develop the standard and
      even months to validate the standard. A marginal logistic regression analysis was
      used to develop the standard. The decision to divert ambulances was used as the
      criterion for ED crowding. RESULTS: The logistic regression demonstrated
      excellent correlation between the work score and diversion status. At the point
      of maximum inflection of the receiver operating characteristic curve, the work
      score predicted diversion status with 86% sensitivity and 80% specificity.
      CONCLUSIONS: An ED work score was successfully developed and internally
      validated. External validation should be performed before widespread use.

PMID- 16581934
TI  - Measuring crowding: time for a paradigm shift.

PMID- 16581935
TI  - Dr. Death: reflections of death telling.

PMID- 16581939
TI  - Transposon-mediated expansion and diversification of a family of ULP-like genes.
AB  - Transposons comprise a major component of eukaryotic genomes, yet it remains
      controversial whether they are merely genetic parasites or instead significant
      contributors to organismal function and evolution. In plants, thousands of DNA
      transposons were recently shown to contain duplicated cellular gene fragments, a
      process termed transduplication. Although transduplication is a potentially rich
      source of novel coding sequences, virtually all appear to be pseudogenes in rice.
      Here we report the results of a genome-wide survey of transduplication in Mutator
      like elements (MULEs) in Arabidopsis thaliana, which shows that the phenomenon is
      generally similar to rice transduplication, with one important exception:
      KAONASHI (KI). A family of more than 97 potentially functional genes and apparent
      pseudogenes, evidently derived at least 15 MYA from a cellular small ubiquitin
      like modifier-specific protease gene, KI is predominantly located in potentially
      autonomous non-terminal inverted repeat MULEs and has evolved under purifying
      selection to maintain a conserved peptidase domain. Similar to the associated
      transposase gene but unlike cellular genes, KI is targeted by small RNAs and
      silenced in most tissues but has elevated expression in pollen. In an Arabidopsis
      double mutant deficient in histone and DNA methylation with elevated KI
      expression compared to wild type, at least one KI-MULE is mobile. The existence
      of KI demonstrates that transduplicated genes can retain protein-coding capacity
      and evolve novel functions. However, in this case, our evidence suggests that the
      function of KI may be selfish rather than cellular.

PMID- 16581940
TI  - Promoter analysis of MADS-box genes in eudicots through phylogenetic
      footprinting.
AB  - The MIKC MADS-box gene family has been shaped by extensive gene duplications
      giving rise to subfamilies of genes with distinct functions and expression
      patterns. However, within these subfamilies the functional assignment is not that
      clear-cut, and considerable functional redundancy exists. One way to investigate
      the diversity in regulation present in these subfamilies is promoter sequence
      analysis. With the advent of genome sequencing projects, we are now able to exert
      a comparative analysis of Arabidopsis and poplar promoters of MADS-box genes
      belonging to the same subfamily. Based on the principle of phylogenetic
      footprinting, sequences conserved between the promoters of homologous genes are
      thought to be functional. Here, we have investigated the evolution of MADS-box
      genes at the promoter level and show that many genes have diverged in their
      regulatory sequences after duplication and/or speciation. Furthermore, using
      phylogenetic footprinting, a distinction can be made between redundancy,
      neo/nonfunctionalization, and subfunctionalization.

PMID- 16581941
TI  - The stepwise evolution of early life driven by energy conservation.
AB  - Two main theories have emerged for the origin and early evolution of life based
      on heterotrophic versus chemoautotrophic metabolisms. With the exception of a
      role for CO, the theories have little common ground. Here we propose an
      alternative theory for the early evolution of the cell which combines principal
      features of the widely disparate theories. The theory is based on the extant
      pathway for conversion of CO to methane and acetate, largely deduced from the
      genomic analysis of the archaeon Methanosarcina acetivorans. In contrast to
      current paradigms, we propose that an energy-conservation pathway was the major
      force which powered and directed the early evolution of the cell. We envision the
      proposed primitive energy-conservation pathway to have developed sometime after a
      period of chemical evolution but prior to the establishment of diverse protein
      based anaerobic metabolisms. We further propose that energy conservation played
      the predominant role in the later evolution of anaerobic metabolisms which
      explains the origin and evolution of extant methanogenic pathways.

PMID- 16581942
TI  - A sex-specific marker reveals male heterogamety in European tree frogs.
AB  - Most amphibians examined so far show undifferentiated sex chromosomes. The
      heterogametic sex's identity, usually revealed through indirect means, often
      varies among closely related species or even populations (as do sex-linkage
      groups), suggesting great evolutionary instability of the sex-determining genes.
      Here we take advantage of a sex-specific marker that amplifies in several related
      species of European tree frogs (Hyla arborea group) to disclose a homogeneous
      pattern of male heterogamety. Besides relevance for evolutionary studies of sex
      determination in amphibians, our results have potential for addressing practical
      issues in conservation biology because sex reversal by anthropogenic endocrine
      disruptors is considered one possible cause of amphibian decline.

PMID- 16581943
TI  - Regulation of CYP1A1 gene expression by the antioxidant tert-butylhydroquinone.
AB  - CYP1A1, a major phase I enzyme, plays an important role in the metabolism of
      polycyclic aromatic hydrocarbons and in the chemical activation of xenobiotics to
      carcinogenic derivatives. The phenolic antioxidant tert-butylhydroquinone (tBHQ),
      often used as a food preservative, is generally considered to act only as a mono
      functional inducer of phase II enzymes, thereby exerting chemo-protection.
      However, we recently observed that tBHQ elevated the activity of an aryl
      hydrocarbon receptor (AhR) response element (DRE)-driven luciferase reporter in
      human colon carcinoma cells (Caco-2). Therefore, we studied the effects of tBHQ
      on the activity of a DRE-driven reporter, CYP1A1 mRNA expression, and CYP1A
      enzyme activity in Caco-2 cells and human HepG2 hepatoma cells. We found tBHQ
      caused induction of reporter activity and CYP1A1 expression and activity in Caco
      2 and HepG2 cells. Moreover, tBHQ combined with 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) increased reporter activity and mRNA expression in Caco-2 cells in
      an additive manner. By contrast, tBHQ decreased TCDD-mediated induction of
      reporter activity and CYP1A1 mRNA expression in HepG2 cells. Resveratrol, an AhR
      antagonist, repressed the induction of CYP1A1 by tBHQ. Cotransfection of HepG2
      cells with a dominant negative AhR nuclear translocator mutant abolished the tBHQ
      induced CYP1A1 reporter activity. These findings indicate that CYP1A1 may be
      induced by the antioxidant tBHQ via an AhR-dependent mechanism.

PMID- 16581944
TI  - Stereoselective metabolism of endosulfan by human liver microsomes and human
      cytochrome P450 isoforms.
AB  - Endosulfan (6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,3,4
      benzo(e)dioxathiepin-3-oxide) is a broad-spectrum chlorinated cyclodiene
      insecticide. This study was performed to elucidate the stereoselective metabolism
      of endosulfan in human liver microsomes and to characterize the cytochrome P450
      (P450) enzymes that are involved in the metabolism of endosulfan. Human liver
      microsomal incubation of endosulfan in the presence of NADPH resulted in the
      formation of the toxic metabolite, endosulfan sulfate. The intrinsic clearances
      (CL(int)) of endosulfan sulfate from beta-endosulfan were 3.5-fold higher than
      those from alpha-endosulfan, suggesting that beta-endosulfan would be cleared
      more rapidly than alpha-endosulfan. Correlation analysis between the known P450
      enzyme activities and the rate of the formation of endosulfan sulfate in the 14
      human liver microsomes showed that alpha-endosulfan metabolism is significantly
      correlated with CYP2B6-mediated bupropion hydroxylation and CYP3A-mediated
      midazolam hydroxylation, and that beta-endosulfan metabolism is correlated with
      CYP3A activity. The P450 isoform-selective inhibition study in human liver
      microsomes and the incubation study of cDNA-expressed enzymes also demonstrated
      that the stereoselective sulfonation of alpha-endosulfan is mediated by CYP2B6,
      CYP3A4, and CYP3A5, and that that of beta-endosulfan is transformed by CYP3A4 and
      CYP3A5. The total CL(int) values of endosulfan sulfate formation catalyzed by
      CYP3A4 and CYP3A5 were consistently higher for beta-endosulfan than for the alpha
      form (CL(int) of 0.67 versus 10.46 microl/min/pmol P450, respectively). CYP2B6
      enantioselectively metabolizes alpha-endosulfan, but not beta-endosulfan. These
      findings suggest that the CYP2B6 and CYP3A enzymes are major enzymes contributing
      to the stereoselective disposition of endosulfan.

PMID- 16581945
TI  - Quinacrine is mainly metabolized to mono-desethyl quinacrine by CYP3A4/5 and its
      brain accumulation is limited by P-glycoprotein.
AB  - Quinacrine (QA), an antimalarial drug used for over seven decades, has been found
      to have potent antiprion activity in vitro. To determine whether QA can be used
      to treat prion diseases, we investigated its metabolism and ability to traverse
      the blood-brain barrier in mice. In vitro and in vivo, we identified by liquid
      chromatography-tandem mass spectrometry the major metabolic pathway of QA as N
      desethylation and compared our results with an authentic reference compound. The
      major human cytochrome (P450) isoforms involved in QA mono-desethylation were
      identified as CYP3A4/5 by using specific chemical and antibody inhibition as well
      as cDNA-expressed P450 studies. QA transport from the basolateral to apical side
      in multidrug resistance protein 1 gene (MDR1)-transfected Madin-Darby canine
      kidney (MDCK) cells was markedly greater than in control MDCK cells and was
      inhibited by the potent P-glycoprotein (P-gp) inhibitor GG918 (N-(4-[2-(1,2,3,4
      tetrahydro-6,7-dimethoxy-2-iso-1-quinolynyl)-ethyl]-phenyl)-9,10-dihydro-5
      methoxy-9-oxo-4-acridine carboxamine). In MDR1-knockout (KO) mice, QA brain
      levels were 6 to 9 times higher after a single i.v. dose of 2 mg/kg QA and 49
      times higher after multiple oral doses of 10 mg/kg/day QA for 7 days, compared
      with those in wild-type (WT) FVB mice. In contrast, the QA levels in plasma,
      liver, spleen, and kidney were similar after a single 2 mg/kg i.v. dose and <2
      times greater after 10 mg/kg oral doses in MDR1-KO mice compared with WT mice.
      These results indicate that P-gp plays a critical role in transporting QA from
      the brain.

PMID- 16581946
TI  - Induction of detoxifying enzymes in rodent white adipose tissue by aryl
      hydrocarbon receptor agonists and antioxidants.
AB  - The liver is the main organ of drug metabolism, but the expression and induction
      by xenobiotics of drug-metabolizing enzymes is also often observed in
      extrahepatic tissues. Recently, we reported that lipophilic cytochrome P450
      inducers, beta-naphthoflavone (BNF), phenobarbital, and dexamethasone, induced
      CYP1, CYP2B, and CYP3A enzymes, respectively, in rat epididymal white adipose
      tissue (WAT) at both mRNA and protein levels. To further confirm the xenobiotic
      induced expression of drug-metabolizing enzymes in adipose tissue, we studied the
      induction of CYP1A1 and other detoxifying enzymes by aryl hydrocarbon receptor
      (AhR) agonists and antioxidants. BNF increased CYP1A1 mRNA levels in several
      visceral WATs (epididymal, perirenal, and mesenteric) to a greater degree than in
      subcutaneous WAT in rats. Using C57BL/6 and DBA/2 mice with different
      responsiveness to aryl hydrocarbons and detecting cytoplasmic levels of AhR
      proteins, we have demonstrated that AhR mediates this CYP1A1 induction by BNF in
      WAT. Moreover, the NF-E2-related factor 2 (Nrf2)/antioxidant responsive element
      pathway is also functional in WAT, since BNF, which is known to activate both AhR
      and Nrf2, and antioxidants including tert-butylhydroquinone, 1-chloro-2,4
      dinitrobenzene, and menadione induced the expression of Nrf2-target genes (NAD
      (P)H:quinone oxidoreductase, glutathione S-transferase A subunits, and heme
      oxygenase-1) in rats and mice. These results suggest that both AhR and Nrf2
      pathways are active in WAT and that lipophilic compounds accumulated in WAT can
      activate these transcription factors to increase detoxification capability in the
      tissue.

PMID- 16581947
TI  - Hepatitis C virus core protein promotes proliferation of human hepatoma cells
      through enhancement of transforming growth factor alpha expression via activation
      of nuclear factor-kappaB.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of human
      hepatocellular carcinoma (HCC). The precise mechanism of hepatocarcinogenesis in
      humans by HCV is currently unclear. It was recently shown, however, that
      transgenic mice with the HCV core gene often develop HCC, suggesting tumorigenic
      activity of the HCV core protein. Further, the HCV core protein expressed in
      HepG2 cells transfected with the core gene was shown to stimulate proliferation
      of transfectants through activation of nuclear factor-kappaB (NF-kappaB). The
      downstream target molecule(s) of NF-kappaB activated by the HCV core protein to
      evoke cell proliferation is not yet identified. Transforming growth factor (TGF)
      alpha, which is often overexpressed in various tumour tissues such as HCC, has
      been shown to stimulate hepatocyte proliferation through activation of the
      mitogen-activated protein kinase or extracellular signal-related protein kinase
      (MAPK/ERK) cascade. AIMS: To explore the possibility that TGFalpha might be a
      target molecule for NF-kappaB activated by the HCV core, and that TGFalpha
      participates in the growth promotion of the core transfectants in an autocrine
      manner, activating the MAPK/ERK pathway. METHODS: A HCV core expression vector
      was transfected into human hepatoma Huh-7, HepG2 and Hep3B cells. NF-kappaB
      activity was examined by an electrophoretic mobility shift assay. TGFalpha
      transcription was assessed by a luciferase reporter assay. TGFalpha protein was
      determined by immunoblot and ELISA. MAPK/ERK activity was examined by an in vitro
      kinase assay. Cell proliferation was assessed by a water-soluble tetrazolium salt
      1 assay. RESULTS: In the HCV core transfectants, NF-kappaB bound to the kappaB
      site in the TGFalpha proximal promoter region, resulting in an increase in
      TGFalpha transcription. Immunoblot as well as ELISA showed increased TGFalpha
      expression in the HCV core transfectants. SN50, a specific inhibitory peptide for
      NF-kappaB, cancelled HCV core-induced TGFalpha expression. HCV core protein
      increased cell proliferation as well as ERK activity of the HCV core
      transfectants as compared with the mock transfectants. The growth-promoting
      activity and activation of ERK by the HCV core protein were negated by treatment
      with anti-TGFalpha antibodies. CONCLUSIONS: These results suggest that the HCV
      core protein promotes proliferation of human hepatoma cells by activation of the
      MAPK/ERK pathway through up regulation of TGFalpha transcription via activation
      of NF-kappaB. Our finding provides a new insight into the mechanism of
      hepatocarcinogenesis by HCV infection.

PMID- 16581949
TI  - Effect of ketamine on dendritic arbor development and survival of immature
      GABAergic neurons in vitro.
AB  - Ketamine, a noncompetitive antagonist of the N-methyl-D-aspartate type of
      glutamate receptors, was reported to induce neuronal cell death when administered
      to produce anesthesia in young rodents and monkeys. Subanesthetic doses of
      ketamine, as adjuvant to postoperative sedation and pain control, are also
      frequently administered to young children. However, the effects of these low
      concentrations of ketamine on neuronal development remain unknown. The present
      study was designed to evaluate the effects of increasing concentrations (0.01-40
      microg/ml) and durations (1-96 h) of ketamine exposure on the differentiation and
      survival of immature gamma-aminobutyric acidergic (GABAergic) interneurons in
      culture. In line with previous studies (Scallet et al., 2004), we found that a 1
      h-long exposure to ketamine at concentrations > or = 10 microg/ml was sufficient
      to trigger cell death. At lower concentrations of ketamine, cell loss was only
      observed when this drug was chronically (> 48 h) present in the culture medium.
      Most importantly, we found that a single episode of 4-h-long treatment with 5
      microg/ml ketamine induced long-term alterations in dendritic growth, including a
      significant (p < 0.05) reduction in total dendritic length and in the number of
      branching points compared to control groups. Finally, long-term exposure (> 24 h)
      of neurons to ketamine at concentrations as low as 0.01 microg/ml also severely
      impaired dendritic arbor development. These results suggest that, in addition to
      its dose-dependent ability to induce cell death, even very low concentrations of
      ketamine could interfere with dendritic arbor development of immature GABAergic
      neurons and thus could potentially interfere with the development neural
      networks.

PMID- 16581948
TI  - The utility of the guppy (Poecilia reticulata) and medaka (Oryzias latipes) in
      evaluation of chemicals for carcinogenicity.
AB  - There has been considerable interest in the use of small fish models for
      detecting potential environmental carcinogens. In this study, both guppies
      (Poecilia reticulata) and medaka (Oryzias latipes) were exposed in the aquaria
      water to three known rodent carcinogens for up to 16 months. Nitromethane, which
      caused mammary gland tumors by inhalation exposure in female rats, harderian
      gland and lung tumors in male and female mice, and liver tumors in female mice by
      inhalation, failed to increase tumors in either guppies or medaka. Propanediol,
      which when given in the feed was a multisite carcinogen in both sexes of rats and
      mice, caused increased liver tumors in male guppies and male medaka. There was
      reduced survival in female guppies and no increased tumors in female medaka.
      1,2,3-Trichloropropane, which when administered by oral gavage was a multisite
      carcinogen in both sexes of rats and mice, caused an increased incidence of
      tumors in the liver of both male and female guppies and medaka and in the
      gallbladder of male and female medaka. The results of this study demonstrate that
      for these three chemicals, under these specific exposure conditions, the fish
      appear less sensitive and have a narrower spectrum of tissues affected than
      rodents. These results suggest that fish models are of limited utility in
      screening unknown chemicals for potential carcinogenicity.

PMID- 16581950
TI  - Juvenile idiopathic arthritis: a review for the pediatrician.

PMID- 16581951
TI  - Laryngomalacia and tracheomalacia: common dynamic airway lesions.

PMID- 16581953
TI  - Rabies.

PMID- 16581952
TI  - Cat-scratch disease.

PMID- 16581954
TI  - Probiotics.

PMID- 16581955
TI  - Consultation with the specialist: who needs allergy testing and how to get it
      done.

PMID- 16581956
TI  - Index of suspicion.

PMID- 16581958
TI  - Hyperthyroidism.

PMID- 16581957
TI  - Corrosive ingestions.

PMID- 16581959
TI  - Fluconazole.

PMID- 16581960
TI  - Synchronous selection of homing peptides for multiple tissues by in vivo phage
      display.
AB  - In vivo phage display is a technology used to reveal organ-specific vascular
      ligand-receptor systems in animal models and, recently, in patients, and to
      validate them as potential therapy targets. Here, we devised an efficient
      approach to simultaneously screen phage display libraries for peptides homing to
      any number of tissues without the need for an individual subject for each target
      tissue. We tested this approach in mice by selecting homing peptides for six
      different organs in a single screen and prioritizing them by using software
      compiled for statistical validation of peptide biodistribution specificity. We
      identified a number of motif-containing biological candidates for ligands binding
      to organ-selective receptors based on similarity of the selected peptide motifs
      to mouse proteins. To demonstrate that this methodology can lead to targetable
      ligand-receptor systems, we validated one of the pancreas-homing peptides as a
      mimic peptide of natural prolactin receptor ligands. This new comprehensive
      strategy for screening phage libraries in vivo provides an advantage over the
      conventional approach because multiple organs internally control for organ
      selectivity of each other in the successive rounds of selection. It may prove
      particularly relevant for patient studies, allowing efficient high-throughput
      selection of targeting ligands for multiple organs in a single screen.

PMID- 16581961
TI  - Signaling pathways mediating VEGF165-induced calcium transients and membrane
      depolarization in human endothelial cells.
AB  - Cytosolic calcium and membrane potential were monitored simultaneously in
      quiescent human umbilical vein endothelial cells (HUVEC) exposed to vascular
      endothelial growth factor (VEGF)165 using the fluorescent indicators indo-1 AM
      and DiSBAC2(3), respectively. Application of VEGF165 to cells elicits a rapid
      rise in cytosolic calcium followed by a slower decline toward control values.
      Peak calcium is associated with a slight membrane hyperpolarization; however, as
      calcium falls toward control, a strong depolarization develops and is sustained
      throughout a 10-min period of VEGF165 stimulation. Both the VEGF165-mediated rise
      in cytosolic calcium and membrane depolarization are eliminated by inhibitors of
      VEGFR-2, tyrosine kinase, src kinase and inositol-1,4,5 triphosphate-operated
      calcium channels. Calcium entry, which is initially facilitated by transient
      hyperpolarization, is restricted by a substantial, sustained depolarization that
      developed during the downstroke of the calcium spike. Inhibition of plasmalemmal
      calcium channels diminished the magnitude and duration of the calcium spike,
      suggesting that extracellular calcium influx, secondary to stores release, is a
      significant component of the calcium transient. Inhibition of chloride channels
      substantially reduced membrane depolarization. In addition, the depolarization is
      modulated by PI3 kinase in a ras-independent manner. In summary, intracellular
      calcium and membrane potential are influenced by several key signaling cascades
      of VEGFR-2 activation in HUVEC.

PMID- 16581962
TI  - Science fraud: from patchwork mouse to patchwork data.

PMID- 16581963
TI  - Antoni Van Leeuwenhoek, FRS on Vermeer: a figment of the imagination.

PMID- 16581964
TI  - The sopranos: post-op virtuosi.

PMID- 16581966
TI  - Author, author burning bright; author, author are you right?

PMID- 16581968
TI  - Is the Rac GTPase-activating toxin CNF1 a smart hijacker of host cell fate?
AB  - The term mitotic catastrophe (MC) was coined to describe the mammalian cell death
      caused by aberrant mitosis. MC occurs with features that are fundamentally
      different from those typifying other forms of cell death, including apoptosis. We
      report here for the first time that the Rac-activating toxin CNF1 interferes with
      the occurrence of MC and leads to aneuploidy and multinucleation. This seems to
      be in line with the anti-apoptotic activity of the toxin and consistent with the
      hypothesis that points at CNF1 as a toxin bearing a carcinogenic potential.

PMID- 16581967
TI  - Sialic acid binding immunoglobulin-like lectins may regulate innate immune
      responses by modulating the life span of granulocytes.
AB  - The regulation of cell death is a key element in building up and maintaining both
      innate and adaptive immunity. A critical role in this process plays the tumor
      necrosis factor (TNF)/nerve growth factor (NGF) receptor family of death
      receptors. Recent work suggests that sialic acid binding immunoglobulin (Ig) 
      like lectins (Siglecs) are also empowered to transmit death signals, at least
      into myeloid cells. Strikingly, death induction by Siglecs is enhanced when cells
      are exposed to proinflammatory survival cytokines. Based on these recent
      insights, we hypothesize that at least some members of the Siglec family regulate
      immune responses via the activation of caspase-dependent and caspase-independent
      cell death pathways.

PMID- 16581969
TI  - Increased susceptibility to ATP via alteration of P2X receptor function in
      dystrophic mdx mouse muscle cells.
AB  - Pathological cellular hallmarks of Duchenne muscular dystrophy (DMD) include,
      among others, abnormal calcium homeostasis. Changes in the expression of specific
      receptors for extracellular ATP in dystrophic muscle have been recently
      documented: here, we demonstrate that at the earliest, myoblast stage of
      developing dystrophic muscle a purinergic dystrophic phenotype arises. In
      myoblasts of a dystrophin-negative muscle cell line established from the mdx
      mouse model of DMD but not in normal myoblasts, exposure to extracellular ATP
      triggered a strong increase in cytoplasmic Ca2+ concentrations. Influx of
      extracellular Ca2+ was stimulated by ATP and BzATP and inhibited by zinc,
      Coomassie Brilliant Blue-G, and KN-62, demonstrating activation of P2X7
      receptors. Significant expression of P2X4 and P2X7 proteins was immunodetected in
      dystrophic myoblasts. Therefore, full-length dystrophin appears, surprisingly, to
      play an important role in myoblasts in controlling responses to ATP. Our results
      suggest that altered function of P2X receptors may be an important contributor to
      pathogenic Ca2+ entry in dystrophic mouse muscle and may have implications for
      the pathogenesis of muscular dystrophies. Treatments aiming at inhibition of
      specific ATP receptors could be of a potential therapeutic benefit.

PMID- 16581970
TI  - Anti-angiogenesis therapy can overcome endothelial cell anergy and promote
      leukocyte-endothelium interactions and infiltration in tumors.
AB  - Tumor escape from immunity, as well as the failure of several anti-cancer
      vaccination and cellular immunotherapy approaches, is suggested to be due to the
      angiogenesis-mediated suppression of endothelial cell (EC) adhesion molecules
      involved in leukocyte-vessel wall interactions. We hypothesized that inhibition
      of angiogenesis would overcome this escape from immunity. We investigated this in
      vivo by means of intravital microscopy and ex vivo by immunohistochemistry in two
      mouse tumor models. Angiogenesis inhibitors anginex, endostatin, and angiostatin,
      and the chemotherapeutic agent paclitaxel were found to significantly stimulate
      leukocyte-vessel wall interactions by circumvention of EC anergy in vivo, i.e.,
      by the up-regulation of endothelial adhesion molecules in tumor vessels. This was
      confirmed by in vitro studies of cultured EC at the protein and mRNA levels. The
      new angiostatic designer peptide anginex was most potent at overcoming EC anergy;
      the enhanced leukocyte-vessel interactions led to an increase in the numbers of
      tumor infiltrating leukocytes. While anginex inhibited tumor growth and
      microvessel density significantly, the amount of infiltrated leukocytes (CD45),
      as well as the number of CD8+ cytotoxic T lymphocytes, was enhanced markedly. The
      current results suggest that immunotherapy strategies can be improved by
      combination with anti-angiogenesis.

PMID- 16581971
TI  - Caloric restriction and intermittent fasting alter spectral measures of heart
      rate and blood pressure variability in rats.
AB  - Dietary restriction (DR) has been shown to increase life span, delay or prevent
      age-associated diseases, and improve functional and metabolic cardiovascular risk
      factors in rodents and other species. To investigate the effects of DR on beat-to
      beat heart rate and diastolic blood pressure variability (HRV and DPV) in male
      Sprague-Dawley rats, we implanted telemetric transmitters and animals were
      maintained on either intermittent fasting (every other day feeding) or calorie
      restricted (40% caloric reduction) diets. Using power spectral analysis, we
      evaluated the temporal profiles of the low- and high-frequency oscillatory
      components in heart rate and diastolic blood pressure signals to assess cardiac
      autonomic activity. Body weight, heart rate, and systolic and diastolic blood
      pressure were all found to decrease in response to DR. Both methods of DR
      produced decreases in the low-frequency component of DPV spectra, a marker for
      sympathetic tone, and the high-frequency component of HRV spectra, a marker for
      parasympathetic activity, was increased. These parameters required at least 1
      month to become maximal, but returned toward baseline values rapidly once rats
      resumed ad libitum diets. These results suggest an additional cardiovascular
      benefit of DR that merits further studies of this potential effect in humans.

PMID- 16581972
TI  - Prostaglandin H synthase-catalyzed bioactivation of amphetamines to free radical
      intermediates that cause CNS regional DNA oxidation and nerve terminal
      degeneration.
AB  - Reactive oxygen species (ROS) are implicated in amphetamine-initiated
      neurodegeneration, but the mechanism is unclear. Here, we show that amphetamines
      are bioactivated by CNS prostaglandin H synthase (PHS) to free radical
      intermediates that cause ROS formation and neurodegenerative oxidative DNA
      damage. In vitro incubations of purified PHS-1 with 3,4-methylenedioxyamphetamine
      (MDA) and methamphetamine (METH) demonstrated PHS-catalyzed time- and
      concentration-dependent formation of an amphetamine carbon- and/or nitrogen
      centered free radical intermediate, and stereoselective oxidative DNA damage,
      evidenced by 8-oxo-2'-deoxyguanosine (8-oxo-dG) formation. Similarly in vivo, MDA
      and METH caused dose- and time-dependent DNA oxidation in multiple brain regions,
      remarkably dependent on the regional PHS levels, including the striatum and
      substantia nigra, wherein neurodegeneration of dopaminergic nerve terminals was
      evidenced by decreased immunohistochemical staining of tyrosine hydroxylase.
      Motor impairment using the rotarod test was evident within 3 wk after the last
      drug dose, and persisted for at least 6 months. Pretreatment with the PHS
      inhibitor acetylsalicylic acid blocked MDA-initiated DNA oxidation and protected
      against functional motor impairment for at least 1.5 months after drug treatment.
      This is the first direct evidence for PHS-catalyzed bioactivation of amphetamines
      causing temporal and regional differences in CNS oxidative DNA damage directly
      related to structural and functional neurodegenerative consequences.

PMID- 16581973
TI  - Human cardiac myosin autoantibodies impair myocyte contractility: a cause-and
      effect relationship.
AB  - The functional relevance of autoantibodies (Abs) against cardiac myosin (CM) in
      clinical idiopathic dilated cardiomyopathy (DCM) remains controversial. The study
      sought to determine effects of human Abs affinity-purified (AF) by immunoaffinity
      column chromotography on excitation-contraction coupling in isolated myocytes.
      Effects of CM-Abs from heart failure patients with DCM (n=19) and ischemic heart
      disease (IHD, n=19) on contractility, L-type Ca2+ current, and Ca2+ transients in
      continuously perfused rat ventricular myocytes were studied. Immunofluorescence
      studies using confocal microscopy were carried out to determine whether Abs were
      internalized. AF-Abs from either group did not differ in IgG titer but differed
      in their elution profiles. The IgG3 subclass response was higher in AF fractions
      from DCM (21%) than IHD (5%) patients. The Abs reduced the capacity of field
      stimulated myocytes to contract in a dose-dependent manner. Inhibition of
      contraction, as a percentage of untreated cells, was greater with DCM than IHD
      Abs (P=0.004), and the effect was independent of Ab titer. An increase in
      frequency of the beating myocytes (0.2 to 3.0 Hz) raised peak systolic and
      diastolic levels of [Ca2+]i of cells treated with DCM but not IHD-Abs (P<0.005).
      The AF-Abs were not internalized by myocytes and had no effect on L-type Ca2+
      currents. The altered sensitivity of the myofilaments to [Ca2+]i by CM-Abs may
      represent a potential mechanism of autoantibody-mediated impairment in clinical
      DCM.

PMID- 16581975
TI  - Deficiency of TNF receptors suppresses microglial activation and alters the
      susceptibility of brain regions to MPTP-induced neurotoxicity: role of TNF-alpha.
AB  - Enhanced expression of tumor necrosis factor (TNF) -alpha, is associated with the
      neuropathological effects underlying disease-, trauma- and chemically induced
      neurodegeneration. Previously, we have shown that deficiency of TNF receptors
      protects against MPTP-induced striatal dopaminergic neurotoxicity, findings
      suggestive of a role for TNF-alpha in neurodegeneration. Here, we demonstrate
      that deficiency of TNF receptors suppresses microglial activation and alters the
      susceptibility of brain regions to MPTP. MPTP-induced expression of microglia
      derived factors, TNF-alpha, MCP-1, and IL-1alpha, preceded the degeneration of
      striatal dopaminergic nerve terminals and astrogliosis, as assessed by loss of
      striatal dopamine and TH, and an increase in striatal GFAP. Pharmacological
      neuroprotection with the dopamine reuptake inhibitor, nomifensine, abolished
      striatal dopaminergic neurotoxicity and associated microglial activation.
      Similarly, in mice lacking TNF receptors, microglial activation was suppressed,
      findings consistent with a role for TNF-alpha in striatal MPTP neurotoxicity. In
      the hippocampus, however, TNF receptor-deficient mice showed exacerbated neuronal
      damage after MPTP, as evidenced by Fluoro Jade-B staining (to identify
      degenerating neurons) and decreased microtubule-associated protein-2 (MAP-2)
      immunoreactivity. These effects were not accompanied by microglial activation,
      but were associated with increased oxidative stress (nitrosylation of tyrosine
      residues). These findings suggest that TNF-alpha exerts a
      neurotrophic/neuroprotective effect in hippocampus. The marked differences we
      observed in the regional density, distribution and/or activity of microglia and
      microglia-derived factors may influence the region-specific role for this cell
      type. Taken together, our results are indicative of a region-specific and dual
      role for TNF-alpha in the brain: a promoter of neurodegeneration in striatum and
      a protector against neurodegeneration in hippocampus.

PMID- 16581974
TI  - Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell
      mediated cardiac protection and functional improvement.
AB  - We previously reported that intramyocardial injection of bone marrow-derived
      mesenchymal stem cells overexpressing Akt (Akt-MSCs) inhibits ventricular
      remodeling and restores cardiac function measured 2 wk after myocardial
      infarction. Here, we report that the functional improvement occurs in < 72 h.
      This early remarkable effect cannot be readily attributed to myocardial
      regeneration from the donor cells. Thus, we hypothesized that paracrine actions
      exerted by the cells through the release of soluble factors might be important
      mechanisms of tissue repair and functional improvement after injection of the Akt
      MSCs. Indeed, in the current study we demonstrate that conditioned medium from
      hypoxic Akt-MSCs markedly inhibits hypoxia-induced apoptosis and triggers
      vigorous spontaneous contraction of adult rat cardiomyocytes in vitro. When
      injected into infarcted hearts, the Akt-MSC conditioned medium significantly
      limits infarct size and improves ventricular function relative to controls.
      Support to the paracrine hypothesis is provided by data showing that several
      genes, coding for factors (VEGF, FGF-2, HGF, IGF-I, and TB4) that are potential
      mediators of the effects exerted by the Akt-MSC conditioned medium, are
      significantly up-regulated in the Akt-MSCs, particularly in response to hypoxia.
      Taken together, our data support Akt-MSC-mediated paracrine mechanisms of
      myocardial protection and functional improvement.

PMID- 16581976
TI  - Novel guanine nucleotide exchange factor GEFmeso of Drosophila melanogaster
      interacts with Ral and Rho GTPase Cdc42.
AB  - This article reports the identification and characterization of a DBL-like
      guanine nucleotide exchange factor (GEF) in Drosophila, called GEFmeso, as a
      novel binding target of the Ras-like GTPase Ral. Previous studies suggested that
      some aspects of Ral activity, which is involved in multiple cellular processes,
      are mediated through regulation of Rho GTPases. Here we show in vitro association
      of GEFmeso with the GTP-bound active form of Ral and the nucleotide-free form of
      the Rho GTPase Cdc42. GEFmeso fails to bind to other Rho GTPases, showing that
      Cdc42 is a specific interaction partner of this GEF. Unlike Ral and Cdc42, which
      are ubiquitously expressed, GEFmeso exerts distinct spatio-temporal expression
      patterns during embryonic development, suggesting a tissue-restricted function of
      the GEF in vivo. Based on previous observations that mutations in Cdc42 or
      overexpression of mutant alleles of Cdc42 lead to distinct effects on wing
      development, the effects of overexpression of dominant-negative and activated
      versions of Ral on wing development were analyzed. In addition, GEFmeso
      overexpression studies as well as RNAi experiments were performed. The results
      suggest that Ral, GEFmeso and Cdc42 act in the same developmental pathway and
      that GEFmeso mediates activation of Cdc42 in response to activated Ral in the
      context of Drosophila wing development.

PMID- 16581977
TI  - Beta-catenin regulates wound size and mediates the effect of TGF-beta in
      cutaneous healing.
AB  - After cutaneous injury, a variety of cell types are activated to reconstitute the
      epithelial and dermal components of the skin. beta-Catenin plays disparate roles
      in keratinocytes and fibroblasts, inhibiting keratinocyte migration and
      activating fibroblast proliferation, suggesting that beta-catenin could either
      inhibit or enhance the healing process. How beta-catenin functions in concert
      with other signaling pathways important in the healing process is unknown. Wound
      size was examined in mice expressing conditional null or conditional stabilized
      alleles of beta-catenin, regulated by an adenovirus expressing cre-recombinase.
      The size of the wounds in the mice correlated with the protein level of beta
      catenin. Using mice expressing these conditional alleles, we found that the wound
      phenotype imparted by Smad3 deficiency and by the injection of TGFbeta before
      wounding is mediated in part by beta-catenin. TGFbeta was not able to regulate
      proliferation in beta-catenin null fibroblasts, whereas keratinocyte
      proliferation rate was independent of beta-catenin. When mice are treated with
      lithium, beta-catenin-mediated signaling was activated in cutaneous wounds, which
      healed with a larger size. These results demonstrate a crucial role for beta
      catenin in regulating cutaneous wound size. Furthermore, these data implicate
      mesenchymal cells as playing a critical role regulating wound size.

PMID- 16581978
TI  - Genome and EST analyses and expression of a gene family with putative functions
      in insect chemoreception.
AB  - Odorant-binding proteins (OBPs) are thought to be responsible for the transport
      of semiochemicals across hydrophobic interfaces to olfactory receptors. In
      insects, a second class of OBPs with four conserved cysteines has been variously
      named as sensory appendage proteins, olfactory segment-D proteins, and
      chemosensory proteins (CSPs). The physiological functions of these proteins have
      remained elusive. Here we report a comprehensive survey of both genome and
      expressed sequence tags (EST) databases. This showed that CSPs are apparently
      only present in the phylum, Arthropoda, and in two subphyla, Crustacea and
      Uniramia. This is the first report of a putative CSP in Crustacea and suggests
      that the origin of these genes predates the divergence of Uniramia and Crustacea.
      For the Uniramia, we identified 74 new genes encoding putative CSPs of insect
      species from 10 different orders. Using tissue-specific EST libraries, we have
      examined the relative expression of putative CSP genes in many tissues from 22
      insect species suggesting that the genes are expressed widely. One Drosophila
      CSPs is expressed sixfold higher in head than other CSPs. One Bombyx mori CSPs
      was found at a very high level in pheromone gland, and for the first time, six
      CSPs were identified in B. mori compound eyes. The different frequencies of CSP
      transcripts were observed between solitary and gregarious EST libraries of
      Locusta migratoria.

PMID- 16581979
TI  - A transcriptional enhancer that directs telencephalon-specific transgene
      expression in mouse brain.
AB  - Telencephalin (TLCN, intercellular adhesion molecule-5 [ICAM-5]) is a cell
      adhesion molecule belonging to the immunoglobulin superfamily, which plays
      important roles in dendritic morphogenesis and synaptic plasticity. The
      expression of TLCN is restricted to neurons in the most rostral brain segment,
      telencephalon. Here, we examined a transcriptional regulatory mechanism
      underlying the telencephalon-specific expression of TLCN. TLCN gene is located in
      the ICAM gene cluster containing ICAM-1, ICAM-4, and TLCN (ICAM-5) within 30 kb
      on the mouse chromosome 9. The nucleotide sequence of the 5'-flanking region of
      mouse TLCN gene is highly homologous to that of human and dog orthologs,
      suggesting the presence of important regulatory elements for its transcription.
      To determine the telencephalon-specific enhancer region, we generated several
      lines of transgenic mice that harbor transgenes consisting of different length of
      the 5'-flanking region of mouse TLCN gene (3.9, 1.5, 1.1, and 0.2 kb) fused to
      humanized renilla green fluorescent protein cDNA as a fluorescent reporter.
      Consequently, we identified a crucial region between 1.1 and 0.2 kb upstream of
      the transcription start site that directs the telencephalon-specific expression.
      This enhancer was applied to the Cre/loxP-mediated conditional expression system
      to generate several transgenic lines with different patterns of recombination in
      the telencephalon and will be further used as a powerful tool for genetic
      manipulation in the telencephalic neurons.

PMID- 16581980
TI  - A neural system for learning about object function.
AB  - Does our ability to visually identify everyday objects rely solely on access to
      information about their appearance or on a more distributed representation
      incorporating other object properties? Using functional magnetic resonance
      imaging, we addressed this question by having subjects visually match pictures of
      novel objects before and after extensive training to use these objects to perform
      specific tool-like tasks. After training, neural activity emerged in regions
      associated with the motion (left middle temporal gyrus) and manipulation (left
      intraparietal sulcus and premotor cortex) of common tools, whereas activity
      became more focal and selective in regions representing their visual appearance
      (fusiform gyrus). These findings indicate that this distributed network is
      automatically engaged in support of object identification. Moreover, the regions
      included in this network mirror those active when subjects retrieve information
      about tools and their properties, suggesting that, as a result of training, these
      previously novel objects have attained the conceptual status of "tools."

PMID- 16581981
TI  - Sequential auditory scene analysis is preserved in normal aging adults.
AB  - Normal aging is accompanied by speech perception difficulties, especially in
      adverse listening situations such as a cocktail party. To assess whether such
      difficulties might be related to impairments in sequential auditory scene
      analysis, event-related brain potentials were recorded from normal-hearing young,
      middle-aged, and older adults during presentation of low (A) tones, high (B)
      tones, and silences (--) in repeating 3 tone triplets (ABA--). The likelihood of
      reporting hearing 2 streams increased as a function of the frequency difference
      between A and B tones (Delta f) to the same extent for all 3 age groups and was
      paralleled by enhanced sensory-evoked responses over the frontocentral scalp
      regions. In all 3 age groups, there was also a progressive buildup in brain
      activity from the beginning to the end of the sequence of triplets, which was
      characterized by an enhanced positivity that peaked at about 200 ms after the
      onset of each ABA--triplet. Similar Delta f- and buildup-related activity also
      occurred over the right temporal cortex, but only for young adults. We conclude
      that age-related difficulties in separating competing speakers are unlikely to
      arise from deficits in streaming and might instead reflect less efficient
      concurrent sound segregation.

PMID- 16581982
TI  - The ferret auditory cortex: descending projections to the inferior colliculus.
AB  - Descending corticofugal projections are thought to play a critical role in
      shaping the responses of subcortical neurons. Here, we examine the origins and
      targets of ferret auditory corticocollicular projections. We show that the
      ectosylvian gyrus (EG), where the auditory cortex is located, can be subdivided
      into middle, anterior, and posterior regions according to the pattern of
      cytochrome oxidase staining and immunoreactivity for the neurofilament antibody
      SMI32. Injection of retrograde tracers in the inferior colliculus (IC) labeled
      large layer V pyramidal cells throughout the EG and adjacent sulci. Each region
      of the EG has a different pattern of descending projections. Neurons in the
      primary auditory fields in the middle EG project to the lateral nucleus (LN) of
      the ipsilateral IC and bilaterally to the dorsal cortex and dorsal part of the
      central nucleus (CN). The projection to these dorsomedial regions of the IC is
      predominantly ipsilateral and topographically organized. The secondary cortical
      fields in the posterior EG target the same midbrain areas but exclude the CN of
      the IC. A smaller projection to the ipsilateral LN also arises from the anterior
      EG, which is the only region of auditory cortex to target tegmental areas
      surrounding the IC, including the superior colliculus, periaqueductal gray,
      intercollicular tegmentum, and cuneiform nucleus. This pattern of
      corticocollicular connectivity is consistent with regional differences in
      physiological properties and provides another basis for subdividing ferret
      auditory cortex into functionally distinct areas.

PMID- 16581983
TI  - Functional cerebral reorganization for auditory spatial processing and auditory
      substitution of vision in early blind subjects.
AB  - Early blind (EB) individuals can recognize bidimensional shapes using a
      prosthesis substituting vision with audition (PSVA) and activate right dorsal
      extrastriate visual cortex during the execution of this task. The present study
      used repetitive transcranial magnetic stimulation (rTMS) to further examine the
      functional role of this structure in the successful use of the PSVA. Moreover, we
      investigated which auditory parameter used in the prosthesis (pitch, intensity,
      or spatial location) might contribute to this occipital activation. Results
      revealed that rTMS applied to right dorsal extrastriate cortex in EB subjects
      interferes with both the PSVA use and the auditory spatial location task but not
      with pitch and intensity discriminations. By contrast, rTMS targeting the same
      cortical areas in sighted subjects did not affect performance on any auditory
      tasks. Early visual deprivation thus leads to functional cerebral cross-modal
      reorganization in the processing of auditory information and auditory-to-visual
      sensory substitution. The findings also point to the specific involvement of the
      dorsal visual stream for auditory spatial processing in blind subjects. Moreover,
      this suggests that sensory substitution prostheses can be developed using these
      additional neural resources to perform tasks that partially compensate for the
      loss of vision.

PMID- 16581984
TI  - 'Look for the logo': Practice Standards Scheme goes public.

PMID- 16581990
TI  - International disease monitoring, October to December 2005.

PMID- 16581992
TI  - Costs to farmers of a tuberculosis breakdown.
AB  - An on-farm survey of 151 cattle farmers who had experienced a bovine tuberculosis
      (Mycobacterium bovis) breakdown on their farms was undertaken in 2003 to assess
      the costs associated with the breakdown. In 90 per cent of cases the cost was
      estimated to be less than 18,513 pounds sterling for dairy herds and less than
      11,462 pounds sterling for beef herds, but with a range from 229 pounds sterling
      to 103,817 pounds sterling. The main cost was the slaughter of reactor cattle.
      For the majority of the farmers, the compensation payments seemed to meet most of
      the costs of their breakdowns, although a majority was still left with net
      losses.

PMID- 16581993
TI  - Efficacy of tulathromycin in the treatment of respiratory disease in pigs caused
      by Actinobacillus pleuropneumoniae.
AB  - The efficacy of a single dose of tulathromycin, a novel triamilide antimicrobial
      of the macrolide class, given at 2.5 mg/kg or 5 mg/kg bodyweight, or three daily
      doses of ceftiofur, given at 3 mg/kg bodyweight, was evaluated in pigs with
      respiratory disease induced experimentally with Actinobacillus pleuropneumoniae.
      On day 0, 100 pigs with clinical signs of respiratory disease were randomly
      assigned to groups of 25 pigs, which were treated with either saline, one of the
      doses of tulathromycin, or ceftiofur. The pigs' rectal temperatures and clinical
      scores for respiratory signs and general attitude were recorded daily until day
      10. Animals withdrawn from the study for welfare reasons were recorded. On day
      10, the animals remaining in the study were weighed, euthanased and examined
      postmortem. Three of the animals treated with saline and one of those treated
      with 2.5 mg/kg tulathromycin were withdrawn from the study, but none of those
      treated with 5 mg/kg tulathromycin or ceftiofur were withdrawn. The least squares
      mean bodyweight gains of the pigs treated with the antimicrobial agents were
      significantly (P<0.05) higher than that of the saline-treated group, and the
      least squares mean percentages of the total lung involvement and incidence of
      respiratory disease associated with A. pleuropneumoniae were significantly
      (P<0.05) lower, but there were no significant differences between the three
      groups of pigs treated with the antimicrobial agents.

PMID- 16581995
TI  - Assessment of a commercial sandwich ELISA in the diagnosis of aspergillosis in
      falcons.
AB  - A commercial sandwich elisa (Platelia Aspergillus EIA; Bio-Rad) developed for the
      detection of galactomannan, a major cell wall constituent of Aspergillus species,
      was tested for its efficacy in the diagnosis of aspergillosis in falcons. Ninety
      serum samples from 50 aspergillosis-positive falcons and 182 samples from 142
      aspergillosis-negative falcons were tested. The sensitivity of the test was only
      12 per cent and its specificity was 95 percent. The test was therefore
      unsatisfactory for detecting galactomannan in the serum samples and cannot be
      used as a screening test for aspergillosis in falcons.

PMID- 16581994
TI  - Prospective study of bacterial overgrowth syndrome in eight dogs.
AB  - Eight dogs with cutaneous lesions, clinical signs and cytological findings
      compatible with bacterial overgrowth syndrome were compared with four healthy
      dogs. The affected dogs were treated for 28 days with 30 mg/kg/day cephalexin.
      The results showed that the syndrome was a superficial cutaneous disorder
      characterised by marked pruritus, greasy seborrhoea, offensive odour, erythema,
      lichenification, hyperpigmentation, excoriations and alopecia involving
      principally the ventral aspect of the body, but no papules, pustules, epidermal
      collarettes or crusts; it was caused by overgrowths of Staphylococcus intermedius
      all over the body surface. Histopathological findings included a superficial,
      perivascular, hyperplastic and spongiotic dermatitis with a mixed inflammatory
      infiltrate, but no lesions suggestive of a true pyoderma. In the affected dogs,
      anti-staphylococcal immunoglobulin G levels were high, but anti-staphylococcal
      immunoglobulin E levels were low, suggesting that staphylococcal hypersensitivity
      is not the underlying pathogenic process. The antibiotic treatment improved the
      condition of all the dogs, but five of the eight had an underlying allergic skin
      disease.

PMID- 16581997
TI  - Renal AA amyloidosis in a dairy cow in Turkey.

PMID- 16581998
TI  - Isolation of Brucella species from a live-stranded striped dolphin (Stenella
      coeruleoalba) in Spain.

PMID- 16581999
TI  - Offering the best to patients.

PMID- 16581996
TI  - Diagnosis and long-term therapy of right-sided heart failure in a yellow-crowned
      amazon (Amazona ochrocephala).

PMID- 16582000
TI  - Defining 'exotic animals'.

PMID- 16582001
TI  - Provisions for emergency slaughter of cattle.

PMID- 16582002
TI  - Use of nasal swabs in diagnosis of respiratory disease.

PMID- 16582003
TI  - Control of badgers and bovine TB.

PMID- 16582004
TI  - Equine viral arteritis.

PMID- 16582005
TI  - Anaesthetic machine warning.

PMID- 16582006
TI  - Nitrite intoxication in sows.

PMID- 16582008
TI  - The aryl hydrocarbon receptor signaling pathway is modified through interactions
      with a Kelch protein.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      with important roles in metabolic adaptation, dioxin toxicology, and vascular
      development. To understand the details of this signal transduction pathway, we
      have used the yeast two-hybrid system to identify proteins that physically
      interact with the AHR in a ligand-dependent manner. Using this strategy, we
      identified a novel modifier of the AHR signaling pathway that we named Ah
      receptor associated protein 3 (ARA3). Coexpression of ARA3 with an AHR chimera in
      yeast and mammalian cells enhances signaling in response to agonists. The human
      full-length cDNA previously was described as influenza virus nonstructural
      protein-1 binding protein (NS1BP). This protein contains four apparent domains-a
      "broad complex/tramtrack/bric-a-brac" (BTB) domain, a "kelch" domain, a "BTB and
      C-terminal kelch" (BACK) domain, and an intervening region (IVR). The carboxyl
      terminus of the AHR "Per-ARNT-Sim" (periodicity/AHR nuclear translocator/simple
      minded) domain and the BACK/IVR domains of ARA3 mediate the AHR-ARA3 interaction.
      The BACK/IVR domains of ARA3 also are sufficient to modify AHR signaling in yeast
      and mammalian cells. In an effort to provide a preliminary model of NS1BP
      activity in AHR signaling, we demonstrate that NS1BP regulates the concentration
      of functional AHR in mammalian cells.

PMID- 16582009
TI  - Locus-specific control of DNA methylation by the Arabidopsis SUVH5 histone
      methyltransferase.
AB  - In Arabidopsis thaliana, heterochromatin formation is guided by double-stranded
      RNA (dsRNA), which triggers methylation of histone H3 at Lys-9 (H3 mK9) and CG
      plus non-CG methylation on identical DNA sequences. At heterochromatin targets
      including transposons and centromere repeats, H3 mK9 mediated by the Su(var)3-9
      homologue 4 (SUVH4)/KYP histone methyltransferase (MTase) is required for the
      maintenance of non-CG methylation by the CMT3 DNA MTase. Here, we show that
      although SUVH4 is the major H3 K9 MTase, the SUVH5 protein also has histone MTase
      activity in vitro and contributes to the maintenance of H3 mK9 and CMT3-mediated
      non-CG methylation in vivo. Strikingly, the relative contributions of SUVH4,
      SUVH5, and a third related histone MTase, SUVH6, to non-CG methylation are locus
      specific. For example, SUVH4 and SUVH5 together control transposon sequences with
      only a minor contribution from SUVH6, whereas SUVH4 and SUVH6 together control a
      transcribed inverted repeat source of dsRNA with only a minor contribution from
      SUVH5. This locus-specific variation suggests different mechanisms for recruiting
      or activating SUVH enzymes at different heterochromatic sequences. The suvh4
      suvh5 suvh6 triple mutant loses both monomethyl and dimethyl H3 K9 at target
      loci. The suvh4 suvh5 suvh6 mutant also displays a loss of non-CG methylation
      similar to a cmt3 mutant, indicating that SUVH4, SUVH5, and SUVH6 together
      control CMT3 activity.

PMID- 16582010
TI  - The plastid protein THYLAKOID FORMATION1 and the plasma membrane G-protein GPA1
      interact in a novel sugar-signaling mechanism in Arabidopsis.
AB  - Mutations in genes encoding components of the heterotrimeric G-protein complex
      were previously shown to confer altered sensitivity to increased levels of D
      glucose. This suggests that G-protein coupling may be a novel sugar-signaling
      mechanism in Arabidopsis thaliana. THYLAKOID FORMATION1 (THF1) is here
      demonstrated in vivo as a Galpha interaction partner that functions downstream of
      the plasma membrane-delimited heterotrimeric G-protein (GPA1) in a D-glucose
      signaling pathway. THF1 is a plastid protein localized to both the outer plastid
      membrane and the stroma. Contact between root plastidic THF1 and GPA1 at the
      plasma membrane occurs at sites where the plastid membrane abuts the plasma
      membrane, as demonstrated by Forster resonance energy transfer (FRET). A probable
      role for THF1 in sugar signaling is demonstrated by both biochemical and genetic
      evidence. Root growth in the thf1-1 null mutant is hypersensitive to exogenous D
      glucose, and THF1-overexpressing roots are resistant to inhibition of growth rate
      by high D-glucose. Additionally, THF1 levels are rapidly degraded by D-glucose
      but not L-glucose. The interaction between THF1 and GPA1 has been confirmed by in
      vitro and in vivo coimmunoprecipitation, FRET analysis, and genetic epistasis and
      provides evidence of a sugar-signaling mechanism between plastids and the plasma
      membrane.

PMID- 16582013
TI  - The molecular perspective: Cisplatin.

PMID- 16582011
TI  - Arabidopsis separase AESP is essential for embryo development and the release of
      cohesin during meiosis.
AB  - To investigate how and when sister chromatid cohesion is released from
      chromosomes in plants, we isolated the Arabidopsis thaliana homolog of separase
      (AESP) and investigated its role in somatic and meiotic cells. AESP is similar to
      separase proteins identified in other organisms but contains several additional
      structural motifs. The characterization of two Arabidopsis T-DNA insertion
      alleles for AESP demonstrated that it is an essential gene. Seeds homozygous for
      T-DNA insertions in AESP exhibited embryo arrest at the globular stage. The
      endosperm also exhibited a weak titan-like phenotype. Transgenic plants
      expressing AESP RNA interference (RNAi) from the meiosis-specific DMC1 promoter
      exhibited alterations in chromosome segregation during meiosis I and II that
      resulted in polyads containing from one to eight microspores. Consistent with its
      predicted role in the release of sister chromatid cohesion, immunolocalization
      studies showed that the removal of SYN1 from chromosome arms and the centromeres
      is inhibited in the RNAi mutants. However, the release of SYN1 during diplotene
      occurred normally, indicating that this process is independent of AESP.
      Therefore, our results demonstrate that AESP plays an essential role in embryo
      development and provide direct evidence that AESP is required for the removal of
      cohesin from meiotic chromosomes.

PMID- 16582014
TI  - Profound bioenergetic abnormalities in peri-infarct myocardial regions.
AB  - Regions of myocardial infarct (MI) are surrounded by a border zone (BZ) of
      normally perfused but dysfunctional myocardium. Although systolic dysfunction has
      been attributed to elevated wall stress in this region, there is evidence that
      intrinsic abnormalities of contractile performance exist in BZ myocardium. This
      study examined whether decreases of high-energy phosphates (HEP) and
      mitochondrial F(1)F(0)-ATPase (mtATPase) subunits typical of failing myocardium
      exist in BZ myocardium of compensated postinfarct remodeled hearts. Eight pigs
      were studied 6 wk after MI was produced by ligation of the left anterior
      descending coronary artery (LAD) distal to the second diagonal. Animals developed
      compensated LV remodeling with a decrease of ejection fraction from 54.6 +/- 5.4%
      to 31 +/- 2.1% (MRI) 5 wk after LAD occlusion. The remote zone (RZ) myocardium
      demonstrated modest decreases of ATP and mtATPase components. In contrast, BZ
      myocardium demonstrated profound abnormalities with ATP levels decreased to 42%
      of normal, and phosphocreatine-to-ATP ratio ((31)P-magnetic resonance
      spectroscopy) decreased from 2.06 +/- 0.19 in normal hearts to 1.07 +/- 0.10,
      with decreases in alpha-, beta-, OSCP, and IF(1) subunits of mtATPase, especially
      in the subendocardium. The reduction of myocardial creatine kinase isoform
      protein expression was also more severe in the BZ relative to the RZ myocardium.
      These abnormalities were independent of a change in mitochondrial content because
      the mitochondrial citrate synthase protein level was not different between the BZ
      and RZ. This regional heterogeneity of ATP content and expression of key enzymes
      in ATP production suggests that energetic insufficiency in the peri-infarct
      region may contribute to the transition from compensated LV remodeling to
      congestive heart failure.

PMID- 16582015
TI  - Ultrafine particulate matter exposure augments ischemia-reperfusion injury in
      mice.
AB  - Epidemiological studies have linked ambient particulate matter (PM) levels to an
      increased incidence of adverse cardiovascular events. Yet little is definitively
      known about the mechanisms accounting for the cardiovascular events associated
      with PM exposure. The goal of this study was to determine the effects of
      ultrafine (<0.1 microm) PM exposure on ischemia-reperfusion (I/R) injury. ICR
      mice were exposed to 100 microg of PM or vehicle by intratracheal instillation.
      Twenty-four hours later, mice were anesthetized with pentobarbital sodium (60
      mg/kg), the left anterior descending coronary artery was ligated for 20 min, flow
      was restored for 2 h, and the resulting myocardial infarct (MI) size was
      evaluated. PM exposure doubled the relative size of the MI compared with the
      vehicle control. No difference was observed in the percentage of the left
      ventricle at risk for ischemia. PM exposure increased the level of oxidative
      stress in the myocardium after I/R. The density of neutrophils in the reperfused
      myocardium was increased by PM exposure, but differences in the number of blood
      leukocytes, expression of adhesion molecules on circulating neutrophils, and
      activation state of circulating neutrophils 24 h after PM exposure could not be
      correlated to the increased I/R injury observed. Additionally, aortas isolated
      from PM-exposed animals and studied in vitro exhibited a reduced endothelium
      dependent relaxation response to acetylcholine. These results indicate that
      exposure to ultrafine PM increases oxidative stress in the myocardium, alters
      vascular reactivity, and augments injury after I/R in a murine model.

PMID- 16582016
TI  - Three-dimensional mechanical properties of porcine coronary arteries: a validated
      two-layer model.
AB  - The normal coronary artery consists of two mechanically distinct layers: intima
      media and adventitia. The objective of this study is to establish a two-layer
      three-dimensional (3-D) stress-strain relation of porcine coronary arteries.
      Experimental measurements were made by a series of biaxial tests (inflation and
      axial extension) of intact coronary arteries and, subsequently, their
      corresponding intima-media or adventitia layer. The Fung-type exponential strain
      energy function was used to describe the 3-D strain-stress relation for each
      layer and the intact wall. A genetic algorithm was used to determine the material
      constants in the Fung-type constitutive equation by curve fitting the
      experimental data. Because one layer must be sacrificed before the other layer
      can be tested, the material property of the missing layer was computed from the
      material constants of the intact vessel and the tested layer. A total of 20
      porcine hearts were used: one group of 10 hearts for the left anterior descending
      artery and another group of 10 hearts for the right coronary artery. Each group
      was further divided into two subgroups of five specimens tested for the intact
      wall and the intima-media layer and for the intact wall and the adventitia layer.
      Our results show statistically significant differences in the material properties
      of the two layers. The mathematical model was validated by experimental stress
      strain data for individual layers. The validated 3-D constitutive model will
      serve as a foundation for formulation of layer-specific boundary value problems
      in coronary physiology and cardiology.

PMID- 16582012
TI  - Plant retromer, localized to the prevacuolar compartment and microvesicles in
      Arabidopsis, may interact with vacuolar sorting receptors.
AB  - Receptors for acid hydrolases destined for the lytic compartment in yeast and
      mammalian cells are retrieved from intermediate, endosomal organelles with the
      help of a pentameric protein complex called the retromer. We cloned the
      Arabidopsis thaliana homologs of the three yeast proteins (Vps35, Vps29, and
      Vps26) constituting the larger subunit of retromer and prepared antisera against
      them. With these antibodies, we demonstrated the presence of a retromer-like
      protein complex in salt extracts prepared from Arabidopsis microsomes. This
      complex is associated with membranes that coequilibrate with prevacuolar
      compartment markers and with high-density sedimenting membranes. Immunogold
      negative staining identified these membranes as 90-nm-diameter coated
      microvesicles. Confocal laser scanning immunofluorescence studies performed on
      tobacco (Nicotiana tabacum) BY-2 cells revealed high degrees of colabeling
      between all three retromer antisera and the prevacuolar compartment (PVC) markers
      PEP12 and vacuolar sorting receptor VSR(At-1). The presence of plant retromer at
      the surface of multivesicular bodies was also demonstrated by immunogold labeling
      of sections obtained from high-pressure frozen/freeze-substituted specimens.
      Treatment of BY-2 cells with wortmannin led to swelling of the PVC and a
      separation of the VPS35 and VSR signals. Preliminary data suggesting that
      retromer interacts with the cytosolic domain of a VSR were obtained by
      immunoprecipitation experiments performed on detergent-solubilized microsomes
      with Vps35 antibodies.

PMID- 16582017
TI  - Leukocyte adherence inhibits adenosine-dependent venular control of arteriolar
      diameter and nitric oxide.
AB  - Venular control of arteriolar perfusion has been the focus of several
      investigations in recent years. This study investigated 1) whether endogenous
      adenosine helps control venule-dependent arteriolar dilation and 2) whether
      venular leukocyte adherence limits this response via an oxidant-dependent
      mechanism in which nitric oxide (NO) levels are decreased. Intravital microscopy
      was used to assess changes in arteriolar diameters and NO levels in rat
      mesentery. The average resting diameter of arterioles (27.5 +/- 1.0 microm)
      paired with venules with minimal leukocyte adherence (2.1 +/- 0.3 per 100-microm
      length) was significantly larger than that of unpaired arterioles (24.5 +/- 0.8
      microm) and arterioles (23.3 +/- 1.3 microm) paired with venules with higher
      leukocyte adherence (9.0 +/- 0.5 per 100-microm length). Local superfusion of
      adenosine deaminase (ADA) induced significant decreases in diameter and
      perivascular NO concentration in arterioles closely paired to venules with
      minimal leukocyte adherence. However, ADA had little effect on arterioles closely
      paired to venules with high leukocyte adherence or on unpaired arterioles. To
      determine whether the attenuated response to ADA for the high-adherence group was
      oxidant dependent, the responses were also observed in arterioles treated with
      10(-4) M Tempol. In the high-adherence group, Tempol fully restored NO levels to
      those of the low-adherence group; however, the ADA-induced constriction remained
      attenuated, suggesting a possible role for an oxidant-independent vasoconstrictor
      released from the inflamed venules. These findings suggest that adenosine- and
      venule-dependent dilation of paired arterioles may be mediated, in part, by NO
      and inhibited by venular leukocyte adherence.

PMID- 16582018
TI  - Bile acids induce adhesion molecule expression in endothelial cells through
      activation of reactive oxygen species, NF-kappaB, and p38.
AB  - Bile acids are synthesized in the liver, stored in gallbladder, and secreted into
      the intestine to aid in the absorption of lipid-soluble nutrients. In addition,
      bile acids also actively participate in regulation of gene expression through
      their ability to act as ligands for the nuclear receptor farnesoid X receptor or
      by activating kinase signaling pathways. Under cholestatic conditions, elevated
      levels of bile acids in the liver induce hepatic inflammation, and because bile
      acid levels are also elevated in the circulation, they might also induce vascular
      inflammation. To test this hypothesis, primary human umbilical vein endothelial
      cells (HUVEC) and human aortic endothelial cells were treated with bile acids,
      and the expression of ICAM-1, VCAM-1, and E-selectin were monitored. The three
      major bile acids found in the circulation, chenodeoxycholic acid, deoxycholic
      acid, and lithocholic acid, all strongly induced both the mRNA and protein
      expression of ICAM-1 and VCAM-1. To delineate the mechanism, the experiments were
      conducted in the presence of various kinase inhibitors. The results demonstrate
      that the bile acid-mediated induction of adhesion molecule expression occurs by
      stimulation of NF-kappaB and p38 MAPK signaling pathways through the elevation in
      reactive oxygen species. The bile acid-induced cell surface expression of ICAM-1
      and VCAM-1 was sufficient to result in the increased adhesion of THP-1 monocytes
      to the HUVEC, suggesting that elevated levels of bile acids in the circulation
      may cause endothelium dysfunction and contribute to the initiation of early
      events associated with vascular lesion formation.

PMID- 16582019
TI  - Cardioprotective effects of rosiglitazone are associated with selective
      overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK.
AB  - Current evidence points to renin-angiotensin system as a key mediator in ischemia
      reperfusion injury. Rosiglitazone, a peroxisome proliferator-activated receptor
      gamma (PPAR-gamma) ligand, has recently been shown to confer cardioprotection
      against ischemia-reperfusion in animal models. We sought to examine the
      expression of ANG II receptors during PPAR-gamma-mediated cardioprotection. Male
      Sprague-Dawley rats (nondiabetic) were fed either regular rat chow (control diet
      group, n = 9) or rosiglitazone-rich diet (rosiglitazone-rich diet group, n = 9)
      and were subjected to 1 h of myocardial ischemia followed by 1 h of reperfusion.
      A third group of rats had only thoracotomy and pericardiotomy and served as a
      sham control group (n = 9). Hemodynamics, infarct size, and expression of ANG II
      type 1 and type 2 receptors (AT1 and AT2) were measured in all groups. There was
      a 58% reduction of infarct size in the rosiglitazone-rich diet group (P < 0.01
      vs. control diet group). Increased myocardial expression of AT(1) receptors in
      the ischemic-reperfused myocardium was attenuated in the rosiglitazone-rich diet
      group (P < 0.05 vs. control diet group). Importantly, myocardial AT2 mRNA and
      protein expression were significantly increased (by >100-fold) in the
      rosiglitazone-rich diet group (P < 0.05). These changes were accompanied by
      inhibition of p42/44 MAPK in the rosiglitazone-rich diet group, while the Akt1
      expression, believed to mediate insulin sensitization, remained similar in all
      three groups. The cardioprotective effects of rosiglitazone against myocardial
      ischemia-reperfusion injury are independent of its insulin-sensitizing properties
      and are associated with significant overexpression of AT2 receptors along with
      inhibition of p42/44 MAPK.

PMID- 16582020
TI  - Alveolar hypoxia induces left ventricular diastolic dysfunction and reduces
      phosphorylation of phospholamban in mice.
AB  - Chronic obstructive pulmonary disease (COPD) may lead to pulmonary hypertension
      (PH) and reduced function of the right ventricle (RV). However, COPD patients may
      also develop left ventricular (LV) diastolic dysfunction. We hypothesized that
      alveolar hypoxia induces LV diastolic dysfunction and changes in proteins
      governing Ca(2+) removal from cytosol during diastole. Mice exposed to 10% oxygen
      for 1, 2, or 4 wk were compared with controls. Cardiac hemodynamics were assessed
      with Doppler echocardiography and a microtransducer catheter under general
      anesthesia. The pulmonary artery blood flow acceleration time was shorter and RV
      pressure was higher after 4 wk of hypoxia compared with controls (both P < 0.05).
      In the RV and LV, 4 wk of hypoxia induced a prolongation of the time constant of
      isovolumic pressure decay (51% RV, 43% LV) and a reduction in the maximum rate of
      decline in pressure compared with control (42% RV, 42% LV, all P < 0.05),
      indicating impaired relaxation and diastolic dysfunction. Alveolar hypoxia
      induced a 38%, 47%, and 27% reduction in Ser16-phosphorylated phospholamban (PLB)
      in the RV after 1, 2, and 4 wk of hypoxia, respectively, and at the same time
      points, Ser16-phosphorylated PLB in the LV was downregulated by 32%, 34%, and 25%
      (all P < 0.05). The amounts of PLB and sarco(endo)plasmic reticulum Ca(2+) ATPase
      (SERCA2a) were not changed. In conclusion, chronic alveolar hypoxia induces
      hypophosphorylation of PLB at Ser16, which might be a mechanism for impaired
      relaxation and diastolic dysfunction in both the RV and LV.

PMID- 16582021
TI  - Poly(ADP-ribose) polymerase-1 hyperactivation and impairment of mitochondrial
      respiratory chain complex I function in reperfused mouse hearts.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1), the most abundant member of the PARP
      family, is a nuclear enzyme that catalyzes ADP-ribose transfer from NAD+ to
      specific acceptor proteins in response to DNA damage. Excessive PARP-1 activation
      is an important cause of infarction and contractile dysfunction in heart tissue
      during interruptions of blood flow. The mechanisms by which PARP-1 inhibition and
      disruption dramatically improve metabolic recovery and reduce oxidative stress
      during cardiac reperfusion have not been fully explored. We developed a mouse
      heart experimental protocol to test the hypothesis that mitochondrial respiratory
      complex I is a downstream mediator of beneficial effects of PARP-1 inhibition or
      disruption. Pharmacological inhibition of PARP-1 activity produced no
      deterioration of hemodynamic function in C57BL/6 mouse hearts. Hearts from PARP-1
      knockout mice also exhibited normal baseline contractility. Prolonged ischemia
      reperfusion produced a selective defect in complex I function distal to the NADH
      dehydrogenase component. PARP-1 inhibition and PARP-1 gene disruption conferred
      equivalent protection against mitochondrial complex I injury and were strongly
      associated with improvement in myocardial energetics, contractility, and tissue
      viability. Interestingly, ischemic preconditioning abolished cardioprotection
      stimulated by PARP-1 gene disruption. Treatment with the antioxidant N-(2
      mercaptopropionyl)-glycine or xanthine oxidase inhibitor allopurinol restored the
      function of preconditioned PARP-1 knockout hearts. This investigation establishes
      a strong association between PARP-1 hyperactivity and mitochondrial complex I
      dysfunction in cardiac myocytes. Our findings advance understanding of metabolic
      regulation in myocardium and identify potential therapeutic targets for
      prevention and treatment of ischemic heart disease.

PMID- 16582022
TI  - Enhanced cell transplantation: preventing apoptosis increases cell survival and
      ventricular function.
AB  - Cell transplantation prevents cardiac dysfunction after myocardial infarction.
      However, because most implanted cells are lost to ischemia and apoptosis, the
      benefits of cell transplantation on heart function could be improved by
      increasing cell survival. To examine this possibility, male Lewis rat aortic
      smooth muscle cells (SMCs; 4 x 10(6)) were pretreated with antiapoptotic Bcl-2
      gene transfection or heat shock and then implanted into the infarcted myocardium
      of anesthetized, syngenic female rats (n = 23 per group). On the first day after
      transplantation, apoptotic SMCs were quantified by using transferase-mediated
      dUTP nick-end labeling staining. On days 7 and 28, grafted cell survival was
      quantified by using real-time PCR, and heart function was assessed with the use
      of echocardiography and the Langendorff apparatus. SMCs given antiapoptotic
      pretreatments exhibited improvements in each measure relative to controls.
      Apoptosis was reduced in Bcl-2-treated cells relative to all other groups (P <
      0.05), whereas survival (P < 0.01) was increased. Heat shock also significantly
      decreased apoptosis and increased survival relative to control groups (P < 0.05
      for group effect), although these effects were less pronounced than in the Bcl-2
      treated group. Further, scar areas were reduced in both Bcl-2- and heat shock
      treated groups relative to controls (P < 0.05), and fractional area change and
      cardiac function were greater (P < 0.05 for both measures). These results
      indicate that antiapoptosis pretreatments reduced grafted SMC loss after
      transplantation and enhanced grafted cell survival and ventricular function,
      which was directly related (r = 0.72; P = 0.002) to the number of surviving
      engrafted cells.

PMID- 16582024
TI  - Beneficial effects of green tea--a review.
AB  - Tea is the most consumed drink in the world after water. Green tea is a 'non
      fermented' tea, and contains more catechins, than black tea or oolong tea.
      Catechins are in vitro and in vivo strong antioxidants. In addition, its content
      of certain minerals and vitamins increases the antioxidant potential of this type
      of tea. Since ancient times, green tea has been considered by the traditional
      Chinese medicine as a healthful beverage. Recent human studies suggest that green
      tea may contribute to a reduction in the risk of cardiovascular disease and some
      forms of cancer, as well as to the promotion of oral health and other
      physiological functions such as anti-hypertensive effect, body weight control,
      antibacterial and antivirasic activity, solar ultraviolet protection, bone
      mineral density increase, anti-fibrotic properties, and neuroprotective power.
      Increasing interest in its health benefits has led to the inclusion of green tea
      in the group of beverages with functional properties. However, although all the
      evidence from research on green tea is very promising, future studies are
      necessary to fully understand its contributions to human health, and advise its
      regular consumption in Western diets, in which green tea consumption is nowadays
      limited and sporadic.

PMID- 16582023
TI  - Cardiac aquaporin expression in humans, rats, and mice.
AB  - Water accumulation in the heart is important in ischemia-reperfusion injury and
      operations performed by using cardiopulmonary bypass, with cardiac dysfunction
      associated with myocardial edema being the principal determinant of clinical
      outcome. As an initial step in determining the role of aquaporin (AQP) water
      channels in myocardial edema, we have assessed the myocardial expression of AQPs
      in humans, rats, and mice. RT-PCR revealed expression of AQP-1, -4, -6, -7, -8,
      and -11 transcripts in the mouse heart. AQP-1, -6, -7, and -11 mRNAs were found
      in the rat heart as well as low levels of AQP-4 and -9. Human hearts contained
      AQP-1, -3, -4, -5, -7, -9, -10, and -11 mRNAs. AQP-1 protein expression was
      confirmed by Western blot analysis in all three species. AQP-4 protein was
      detected in the mouse heart but not in the rat or human heart. To determine the
      potential functional consequences of myocardial AQP expression, water
      permeability was measured in plasma membrane vesicles from myocardial cells of
      wild-type versus various AQP knockout mice. Water permeability was reduced by AQP
      1 knockout but not by AQP-4 or AQP-8 knockout. With the use of a model of
      isolated rat heart perfusion, it was found that osmotic and ischemic stresses are
      not associated with changes in AQP-1 or AQP-4 expression. These studies support a
      possible functional role of AQP-1 in myocardium but indicate that early
      adaptations to osmotic and ischemic stress do not involve transcriptional or
      posttranslational AQP-1 regulation.

PMID- 16582026
TI  - Changes in calcium intake and association with beverage consumption and
      demographics: comparing data from CSFII 1994-1996, 1998 and NHANES 1999-2002.
AB  - BACKGROUND: Consumption of soft drinks has been hypothesized to be negatively
      associated with calcium intake. However, fortification of some foods and
      beverages may have affected calcium intake. OBJECTIVE: The purpose of this study
      was to examine changes in calcium intake and the association of milk consumption
      with key beverage consumption and demographic variables using the most current
      data available. DESIGN: Several techniques were used to describe how age, gender,
      race/ethnicity, and beverage consumption were associated with milk and calcium
      intake using the Continuing Survey of Food Intake by Individuals 1994-1996, 1998
      (CSFII) and the National Health and Nutrition Examination Survey 1999-2002
      (NHANES). Using bivariate and multivariate regression analyses, we examined the
      independent relationships of total non-beverage energy intake, fluid milk
      consumption, non-milk beverage consumption, and demographics with calcium intake.
      RESULTS: During the time period between CSFII and NHANES, milk consumption
      decreased and RCSD consumption increased among children 6-11 y. Calcium intake
      was unaffected. Among other age categories, milk consumption either did not
      change or increased (females 40-59 y), while RCSD consumption increased. Calcium
      intake either did not change or increased in most age-gender categories,
      including adolescent females. Fluid milk consumption exhibited the strongest
      association with calcium intake. Fruit juice consumption was also positively
      associated with calcium intake in most age-gender categories. Consumption of
      other beverages, including RCSD, had little or no association with calcium
      intake. CONCLUSIONS: Consumption of low-fat milk should be encouraged, but
      calcium fortification of certain foods and beverages and calcium supplementation
      may be needed to further increase calcium intake.

PMID- 16582025
TI  - Korean red ginseng rootlets decrease acute postprandial glycemia: results from
      sequential preparation- and dose-finding studies.
AB  - BACKGROUND: Fractionation of a ginseng source to produce differences in the
      ginsenoside profile might influence its effect on postprandial glycemia. To
      explore this possibility and identify an efficacious ginseng for a longterm
      study, we conducted a preparation-finding study of different Korean red ginseng
      (KRG) root fractions followed by a dose-finding study of the most efficacious
      fraction. METHODS: A double-blind, randomized, within-subject design was used in
      both studies. In the preparation-finding study, 7 healthy subjects (sex: 3m:4f,
      age: 32 +/- 4 y, BMI: 24 +/- 2 kg/m2) received 6 g placebo and KRG-rootlets, 
      body, and -H2O extract 40 min before a 50 g-OGTT with finger-prick blood samples
      at -40-, 0-, 15-, 30-, 45-, 60-, 90-, 120-min. In the dose-finding study, 12
      healthy subjects (sex: 9M,3F, age: 29 +/- 3 y, BMI: 22.5 +/- 1 kg/m2) received 0
      g (placebo), 2 g, 4 g, and 6 g of the most efficacious root fraction following
      the same protocol. Ginsenosides were analyzed using HPLC-UV. RESULTS: In the
      preparation-finding study, a wide variation in the ginsenoside profiles was
      achieved across the 3 KRG fractions. This variation coincided with differential
      effects. The main effects of KRG-rootlets (p = 0.050) and time (p < 0.001) and
      their interaction (p < 0.1) were significant. This was reflected in a 29%
      reduction in area under the curve (AUC) by KRG-rootlets compared with placebo (p
      = 0.052). Conversely, neither KRG-H2O extract nor KRG-body affected glycemia.
      Stepwise-multiple regression models identified Rg1 as the sole predictor of mean-
      and AUC postprandial blood glucose. In the dose-finding study, KRG-rootlets were
      tested as the most efficacious fraction. A significant effect of KRG-rootlets
      treatment (mean of 3 doses) but not dose was found. The mean of 3 doses decreased
      AUC by 17% compared with placebo (p = 0.057). CONCLUSIONS: Together the studies
      indicate 2 g KRG-rootlets is sufficient to achieve reproducible reductions in
      postprandial glycemia. But the longterm sustainability of KRG selected using this
      approach remains to be tested.

PMID- 16582027
TI  - Palm olein in the fat blend of infant formulas: effect on the intestinal
      absorption of calcium and fat, and bone mineralization.
AB  - OBJECTIVE: To evaluate the published clinical data on the physiologic effects of
      using palm oil and its low melting fraction, palm olein (PO) as a dominant lipid
      source in the fat blend in infant formulas. DESIGN: A systematic search of
      Medline and the Cochrane Database of Systematic Reviews was performed to retrieve
      studies comparing infants who received infant formulas containing PO with those
      who received infant formulas without PO or which contained synthetic
      triacylglyceride as a source of palmitic acid. Outcomes of interest include
      intestinal fractional absorption of fat, palmitic acid and calcium; and bone
      mass. The effect size for each dependent variable in each published study was
      obtained by standardizing based on the difference in means between non-PO and PO
      group with respect to the standard deviation of the PO group. Trend analysis of
      the outcome of interest was performed when 3 or more between group comparisons
      were available. The comparison of effect size across different studies was based
      on all available data and includes results that showed no significant difference
      between infants fed PO or non-PO study formulas in the outcomes of interest.
      RESULTS: Nine publications were identified with non-PO and PO comparison groups.
      The gestational ages of infants in the published studies were between 28 to 42
      weeks and postnatal ages were birth to 192 days at study onset. Within each
      published study, there was some variability in the effect size between non-PO and
      PO groups. The standardized results were consistently significantly (p < 0.05)
      positive in favor of the feeding with non-PO formulas with respect to increased
      intestinal fractional absorption of fat, palmitic acid and calcium. The latter
      two variables were significantly different by at least 0.6 SD. Bone mass measured
      as total body bone mineral content was significantly higher in the non-PO group
      by at least 0.3 SD. CONCLUSION: The use of PO in infant formulas to match the
      human milk content of palmitic acid has unintended physiological consequences
      including diminished intestinal absorption of fat, palmitic acid and calcium and
      lower bone mass. The avoidance of PO or its substitution with synthetic
      triacylglyceride in infant formulas can prevent this detrimental effect.

PMID- 16582028
TI  - Changes in body weight, body composition and resting metabolic rate (RMR) in
      first-year university freshmen students.
AB  - OBJECTIVES: The purpose of the present study was to document any changes that
      might occur in body weight, body composition, RMR, and dietary intake in newly
      enrolled college freshmen. METHODS: Body weight, RMR by ventilated O(2)
      consumption, body composition by bioelectrical impedance and dietary intakes were
      recorded in 27 first-year college freshmen during their initial 16-week semester.
      RESULTS: Mean body weight increased significantly with time (3.0 lbs; p < 0.001);
      16 subjects (59%) gained >or= 3.0 lbs, while 6 subjects (22%) gained >or= 6 lbs.
      Percent fat mass significantly increased (p < 0.001), while lean body mass
      decreased (p < 0.001). Changes in RMR failed to reach statistical significance;
      however, there was a significant correlation between changes in weight and RMR (r
      = 0.45; p < 0.02). Mean reported calorie intake did not differ significantly
      between the beginning (1905 +/- 664 kcal) and end (1960 +/- 687 kcal) of the
      study. However, the differences ( approximately 55 kcal) are in the range
      necessary to support the mean 3 lb. weight gain. CONCLUSIONS: The present study
      supports the notion that freshmen students, on average, gain weight during their
      first semester; however, this weight gain may be more modest than generally
      perceived. The study also provides important new data on changes in diet, body
      composition and RMR.

PMID- 16582029
TI  - Gender differences in factors associated with nutritional status of older medical
      patients.
AB  - OBJECTIVES: To evaluate gender differences in nutritional risk of older people
      admitted to an acute-care general medical department, and identify gender
      specific risk factors. DESIGN: Cross-sectional study. SETTING: Internal Medicine
      Department in an acute care, university-affiliated hospital in southern Israel.
      SUBJECTS: 204 cognitively intact patients aged 65 and over, admitted during a 12
      month period to a general medical department. MEASURES OF OUTCOME: Evaluation
      included demographic and clinical data consisting of the sum of medical
      conditions and of prescribed medications, evaluation of nutritional status,
      cognitive status, depression assessment and functional ability. Statistical
      analyses were conducted to evaluate the gender specific risk factors for under
      nutrition. RESULTS: 32.5% of the men and 48.1% of the women admitted to an
      internal medicine department were at risk for under-nutrition. Those at
      nutritional risk had a higher rate of depression, lower cognitive and physical
      ability, poorer reported health status and more diagnosed diseases. Nutritional
      risk for men was associated with higher depression score, longer hospitalization,
      and poor appetite. For women, nutritional risk was associated with lower
      functional status and more diagnosed diseases. In a multivariate analysis, being
      a female increased the risk of under-nutrition by 3.3 fold. CONCLUSION: Risk of
      under-nutrition is prevalent among older in-patients and is gender-related.
      Female inpatients are at markedly increased risk for under-nutrition. The
      mechanism of the gender discrepancy in factors related to nutritional
      deterioration is complex and poorly understood.

PMID- 16582030
TI  - The contribution of ready-to-eat cereals to daily nutrient intake and breakfast
      quality in a Mediterranean setting.
AB  - OBJECTIVES: To examine if and how ready-to-eat cereals (RTEC) contribute to the
      quality of the diet of children, adolescents and young adults in a Mediterranean
      setting. METHODS: A random sample of 3534 subjects aged 2 to 24 years in Spain
      was studied. Food and nutrient intakes were determined by a 24 hour recall. RTEC
      consumption was assessed by a quantitative food frequency questionnaire.
      Additional questions on socioeconomic level and nutritional knowledge were
      administered. Cereal consumption was classified into non-consumers and daily
      intakes between 1 and 20g, 21 and 40g, and more than 40g. After excluding the
      underreporters the final sample consisted of 2852 individuals. RESULTS: About
      half of the population (49.8%) reported eating RTEC. Macronutrient profile
      improved with increasing cereal consumption. Intakes of thiamine, riboflavin and
      vitamin B6 increased significantly with increasing consumption of RTEC in all age
      sex groups, whereas niacin and folate intake improved in almost all groups and
      calcium, iron and vitamin D in at least half of the groups. Except for magnesium,
      vitamin B12 and vitamin E in males, consumption of RTEC was significantly
      associated with increased coverage of the daily nutrient requirements for all
      micronutrients studied. Higher levels of RTEC consumption was associated with a
      greater consumption of dairy products, and related to better breakfast quality.
      CONCLUSIONS: Level of RTEC consumption is associated with a better nutritional
      profile in the diets of Spanish children, adolescents and young adults and a
      lower risk for inadequate micronutrient intakes. RTEC consumers have better
      quality breakfasts, in terms of both food choices as well as energy and nutrient
      content.

PMID- 16582031
TI  - Whole cinnamon and aqueous extracts ameliorate sucrose-induced blood pressure
      elevations in spontaneously hypertensive rats.
AB  - OBJECTIVE: Many agents (nutrients, nutraceuticals, and drugs) that enhance
      insulin sensitivity and/or reduce circulating insulin concentrations lower blood
      pressure (BP). Recently, it was reported that cinnamon has the potential to
      favorably influence the glucose/insulin system. Accordingly, the purpose of the
      present study was to examine the effects of dietary cinnamon on systolic BP
      (SBP), and various glucose- and insulin-related parameters in spontaneously
      hypertensive rats (SHR). METHODS: In a series of three experiments, treated SHR
      eating sucrose and non sucrose containing diets were given various amounts of
      cinnamon, cinnamon extracts, or chromium. Then various parameters such as: body
      weight, systolic blood pressure, hematology and blood chemistries were followed
      for three to four weeks. RESULTS: Diets high in sucrose content are associated
      with insulin resistance and the elevation of SBP. Addition to diets of cinnamon
      (8% w/w) reduced the SBP of rats eating sucrose containing diets to virtually the
      same levels as SHR consuming non sucrose containing (only starch) diets. The
      presence of cinnamon in the diet also decreased the SBP of SHR consuming a non
      sucrose-containing diet, suggesting that cinnamon reduces more than just sucrose
      induced SBP elevations--perhaps a genetic component(s) of the elevated BP as
      well. The effects of cinnamon on SBP tended to be dose-dependent. Cinnamon did
      not decrease the levels of blood glucose, but did lower circulating insulin
      concentrations. Aqueous extracts of cinnamon also decreased SBP and lowered the
      circulating levels of fructosamine. CONCLUSIONS: Cinnamon is used for flavor and
      taste in food preparation, but cinnamon may have additional roles in glucose
      metabolism and BP regulation. Therefore, BP regulation may not only be influenced
      favorably by limiting the amounts of dietary substances that have negative
      effects on BP and insulin function but also by the addition of beneficial ones,
      such as cinnamon, that have positive effects.

PMID- 16582032
TI  - Circadian variations in fat content of expressed breast milk from mothers of
      preterm infants.
AB  - BACKGROUND: Little is known about circadian variations of the fat content in
      expressed human milk by mothers of preterm infants. OBJECTIVE: To test the
      hypothesis that the fat content of expressed preterm human milk is higher in
      samples expressed in the evening (i.e. after 3 daily meals) than in the morning
      (after a night-long fast). METHODS: We collected samples of expressed human milk
      obtained from 39 mothers of hospitalized growing preterm infants aged 7-14 days,
      with a gestational age at birth ranging from 26 to 33 weeks, who routinely
      expressed all their milk every 3 hours, during the day time, just before bed
      time, and as soon as they woke up, using a commercial breast pump (Medela AG,
      Baar, Switzerland). One sample was obtained from the first morning expression
      (between 0600 and 0900) and the second from the evening expression (between 2100
      and 2400). The entire quantity of expressed milk was collected, mixed and
      measured in a capillary tube after centrifugation at 9000 rpm for 5 minutes.
      Creamatocrits (CMT) were performed in duplicates. Each sample was read
      independently by 2 investigators who were not aware of the origin and time of
      sampling and the results were averaged. Results are expressed as mean +/- SD, and
      analyses were by paired t-test and regression analysis. RESULTS: CMT was
      significantly higher in evening than in morning samples (7.9 +/- 2.9% vs. 6.6 +/-
      2.8%, P = 0.005). Neither CMT nor the morning-evening difference in CMT
      correlated with gestational age or birthweight. The morning CMT correlated
      significantly with the evening CMT (P < 0.001). CONCLUSIONS: There are
      significant circadian variations in the CMT of expressed preterm human milk. We
      speculate that if higher caloric content of expressed human milk is needed in a
      specific preterm infant, evening sample, if available, should be used
      preferentially.

PMID- 16582034
TI  - Recent national trends in sudden, unexpected infant deaths: more evidence
      supporting a change in classification or reporting.
AB  - The recent US decline in sudden infant death syndrome (SIDS) rates may be
      explained by a shift in how these deaths are classified or reported. To examine
      this hypothesis, the authors compared cause-specific mortality rates for SIDS,
      other sudden, unexpected infant deaths, and cause unknown/unspecified, and they
      evaluated trends in the age and month of death for these causes using 1989-2001
      US linked birth/death certificate data. Reported deaths in state and national
      data were compared to assess underreporting or overreporting. SIDS rates declined
      significantly from 1989-1991 to 1995-1998, while deaths reported as cause
      unknown/unspecified and other sudden, unexpected infant deaths, such as
      accidental suffocation and strangulation in bed (ASSB), remained stable. From
      1999-2001, the decline in SIDS rates was offset by increasing rates of cause
      unknown/unspecified and ASSB. Changes in the cause-specific age at death and
      month of death distributions suggest that cases once reported as SIDS are now
      being reported as ASSB and cause unknown/unspecified. Most of the decline in SIDS
      rates since 1999 is likely due to increased reporting of cause
      unknown/unspecified and ASSB. Standardizing data collection at death scenes and
      improving the reporting of cause of death on death certificates should improve
      national vital records data and enhance prevention efforts.

PMID- 16582035
TI  - Effects of diet and metamorphosis upon the sterol composition of the butterfly
      Morpho peleides.
AB  - Whole body sterol metabolism in insects has seldom been studied. We were able to
      design an appropriate study at a butterfly farm in Belize. We collected six
      larvas of butterfly (Morpho peleides), their food (leaves of Pterocarpus
      bayessii), and their excretions. In addition, six adult butterflies were
      collected. The sterols of the diet, the larva, and adult butterfly were analyzed
      by gas-liquid chromatography. The structures of these sterols were identified by
      digitonin precipitation, GC-MS, and NMR. Four sterols (cholesterol, campesterol,
      stigmasterol, and sitosterol) and a sterol mixture were found in the food, the
      body, and the excreta of the larva. The tissue sterol content of the larva was
      326 microg. They consumed 276 microg of sterols per day. Their excretion was 185
      microg per day as sterols. The total tissue sterol contents of the larva and
      butterfly were similar, but they had different sterol compositions, which
      indicated interconversion of sterols during development. There was a progressive
      increase in the cholesterol content from larva to butterfly and a decrease in the
      content of sitosterol and other plant sterols, which were likely converted to
      cholesterol. Our data indicated an active sterol metabolism in butterfly larva.
      Diet played an important role in determining its sterol composition. During
      metamorphosis, there was an interconversion of sterols. This is the first paper
      documenting the fecal sterol excretion in insects as related to dietary intakes.

PMID- 16582037
TI  - Stress, aging, and mental health.

PMID- 16582033
TI  - Association between carbohydrate intake and serum lipids.
AB  - BACKGROUND: The effect of dietary carbohydrate on blood lipids has received
      considerable attention in light of the current trend in lowering carbohydrate
      intake for weight loss. OBJECTIVES: To evaluate the association between
      carbohydrate intake and serum lipids. METHODS: Blood samples and 24-hour dietary
      and physical activity recall interviews were obtained from each subject at
      quarterly intervals for five consecutive quarters between 1994 and 1998 from 574
      healthy adults in Central Massachusetts. Relationships between serum lipids and
      dietary carbohydrate factors were assessed using linear mixed models and
      adjusting for other risk factors known to be related to blood lipids. Both cross
      sectional and longitudinal results were reported. RESULTS: Cross-sectional
      analysis results from this study suggest that higher total carbohydrate intake,
      percentage of calories from carbohydrate, glycemic index (GI) and/or glycemic
      load (GL) are related to lower high-density lipoprotein cholesterol (HDL-C) and
      higher serum triacylglycerol levels, while higher total carbohydrate intake
      and/or GL are related to lower total and low-density lipoprotein cholesterol (LDL
      C) levels. In a one-year longitudinal analysis, GL was positively associated with
      total and LDL-C levels, and there was an inverse association between percentage
      of calories from carbohydrate and HDL-C levels. CONCLUSIONS: Results suggest that
      there is a complex and predominantly unfavorable effect of increased intake of
      highly processed carbohydrate on lipid profile, which may have implications for
      metabolic syndrome, diabetes, and coronary heart disease. Further studies in the
      form of randomized controlled trials are required to investigate these
      associations and determine the implications for lipid management.

PMID- 16582038
TI  - Avoidant coping partially mediates the relationship between patient problem
      behaviors and depressive symptoms in spousal Alzheimer caregivers.
AB  - OBJECTIVE: Caring for a loved one with Alzheimer disease is a highly stressful
      experience that is associated with significant depressive symptoms. Previous
      studies indicate a positive association between problem behaviors in patients
      with Alzheimer disease (e.g., repeating questions, restlessness, and agitation)
      and depressive symptoms in their caregivers. Moreover, the extant literature
      indicates a robust negative relationship between escape-avoidance coping (i.e.,
      avoiding people, wishing the situation would go away) and psychiatric well-being.
      The purpose of this study was to test a mediational model of the associations
      between patient problem behaviors, escape-avoidance coping, and depressive
      symptoms in Alzheimer caregivers. METHODS: Ninety-five spousal caregivers (mean
      age: 72 years) completed measures assessing their loved ones' frequency of
      problem behaviors, escape-avoidance coping, and depressive symptoms. A
      mediational model was tested to determine if escape-avoidant coping partially
      mediated the relationship between patient problem behaviors and caregiver
      depressive symptoms. RESULTS: Patient problem behaviors were positively
      associated with escape-avoidance coping (beta = 0.38, p < 0.01) and depressive
      symptoms (beta = 0.26, p < 0.05). Escape-avoidance coping was positively
      associated with depressive symptoms (beta = 0.33, p < 0.01). In a final
      regression analysis, the impact of problem behaviors on depressive symptoms was
      less after controlling for escape-avoidance coping. Sobel's test confirmed that
      escape-avoidance coping significantly mediated the relationship between problem
      behaviors and depressive symptoms (z = 2.07, p < 0.05). CONCLUSION: Escape
      avoidance coping partially mediates the association between patient problem
      behaviors and depressive symptoms among elderly caregivers of spouses with
      dementia. This finding provides a specific target for psychosocial interventions
      for caregivers.

PMID- 16582039
TI  - Childhood adversity and psychosocial adjustment in old age.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that higher
      level of childhood adversity is associated with lower level of psychosocial
      adjustment in old age. METHOD: Participants are 253 older persons (mean age:
      79.8, standard deviation: 2.1; 73.9% women) from the Rush Memory and Aging
      Project, a clinicopathologic study of common chronic conditions of old age.
      Childhood adversity was assessed with a 16-item measure based on portions of the
      Childhood Trauma Questionnaire and other inventories. Psychosocial adjustment was
      assessed with multiple measures of neuroticism (i.e., proneness to negative
      emotions) and social engagement. RESULTS: Based in part on a factor analysis,
      composite measures of total adversity, emotional neglect, parental intimidation,
      parental violence, family turmoil, and financial need were developed. In a series
      of linear regression models adjusted for age, sex, own education, and parental
      education, the composite measure of childhood adversity was associated with all
      facets of neuroticism and accounted for more than 13% of the variance in the
      composite neuroticism measure. Emotional neglect and parental intimidation had
      the strongest associations with neuroticism. Childhood adversity was not related
      to frequency of participation in social activities, but more adversity was
      associated with having a smaller network (accounting for 3% of the variance) and
      feeling more emotionally isolated (accounting for 7% of the variance).
      CONCLUSION: Childhood adversity is associated with less adaptive psychosocial
      functioning in old age.

PMID- 16582040
TI  - Posttraumatic stress, depression, and health among older adults in primary care.
AB  - OBJECTIVE: The authors examined 1) rates of trauma and posttraumatic stress (PTS)
      in older adults in primary care; 2) factors related to more posttraumatic stress
      symptoms; and 3) the influence of posttraumatic stress and depression on health
      perceptions and negative health behaviors (i.e., suicidal ideation, smoking, and
      at-risk drinking). METHODS: As part of participation in a study at the
      Philadelphia VAMC and the University of Pennsylvania, a random subset (N = 2,718)
      of older adults (age > or = 65 years) with scheduled primary care visits were
      screened concerning demographics, the General Health Questionnaire-12, suicidal
      thoughts, alcohol consumption, cigarette smoking, perceived health status, PTS,
      and cognitive impairment. RESULTS: The rate of trauma in older adult primary care
      patients was high in both the VA (37%) and university-based clinics (24%). Many
      older adults reported interference from at least one of the three posttraumatic
      stress items assessed (VA, 18%; university-based primary care, 8%). In a model
      including demographic factors, higher PTS and depression were uniquely related to
      more negative health perceptions. In a model including demographic factors, both
      higher PTS and depression were uniquely related to higher likelihood of suicidal
      ideation. In contrast, PTS no longer contributed to a model of smoking once
      depression was included. Neither PTS nor depression significantly contributed to
      a model of at-risk drinking. CONCLUSIONS: Trauma and posttraumatic stress are
      frequent and significant problems for older adults in primary care. Both
      posttraumatic stress and depression are related to more negative health
      perceptions and higher likelihood of suicidal ideation.

PMID- 16582041
TI  - Design decisions to optimize reliability of daytime cortisol slopes in an older
      population.
AB  - OBJECTIVE: The daytime log-cortisol slope appears to be of growing importance in
      studying the relationship between stress and health. How best to estimate that
      slope with minimal burden to the participants and the cost of the study is a
      decision often made without empiric foundation. METHODS: In 50 older
      participants, the authors examined cortisol assay comparability across
      laboratories, assay reliability, test-retest reliability of slopes, and
      comparability of slope estimates for two, three, and four samples per day.
      RESULTS: The authors demonstrate in an older sample that 1) assay reliability is
      a relatively minor issue, that one assay per saliva sample suffices; 2) the use
      of a sample obtained at wake time for each participant appears to be a preferred
      anchor for the slope estimate in comparison to a sample 30 minutes postwake time;
      3) self-reported times appear preferable to automatic time recording; and 4) test
      retest reliability of slopes, however, is not sufficiently high to base a slope
      estimate on one day; minimally two days and preferably three should be required.
      CONCLUSIONS: Whether these conclusions apply to other populations, or using other
      protocols, is not assured, but the study itself provides a model that can be used
      to check research decisions. Unnecessarily imposing a burdensome protocol has
      both ethical and scientific ramifications and should be carefully avoided.

PMID- 16582042
TI  - Ethnicity, stress, and cortisol function in Hispanic and non-Hispanic white
      women: A preliminary study of family dementia caregivers and noncaregivers.
AB  - OBJECTIVE: This study examined differences in psychologic and physiological
      responses to caregiving stress in Hispanic and non-Hispanic white women dementia
      caregivers and noncaregivers. Dependent variables were perceived stress,
      depression, and salivary cortisol. METHOD: Eighty-three women caregivers (20
      Hispanic and 24 non-Hispanic white) and noncaregivers (19 Hispanic and 20 non
      Hispanic white) completed the Perceived Stress Scale (PSS), Center for
      Epidemiological Studies-Depression Scale (CES-D), and collected three saliva
      samples daily for 3 consecutive days. A subsample of 17 Hispanic and 28 non
      Hispanic white participants matched on age and education was used for the main
      analyses. RESULTS: Caregivers had higher levels of 8 am, 5 pm, and 9 pm log
      cortisol as well as higher perceived stress than noncaregivers. Non-Hispanic
      whites had higher depression scores than noncaregivers, but there was no
      significant difference for Hispanics. Hispanics, regardless of caregiving status
      had flatter daytime cortisol slopes than the non-Hispanic whites. Multivariate
      regression analyses showed that both ethnicity and depressive symptoms
      independently predicted daytime cortisol slope. CONCLUSIONS: Results support the
      relationship between chronic stress and hypothalamic-pituitary-adrenal axis
      dysregulation among women dementia caregivers and highlight the need to examine
      further the role of ethnicity and depressive symptoms in their physiological
      responses.

PMID- 16582043
TI  - Cumulative effect of COMT and 5-HTTLPR polymorphisms and their interaction with
      disease severity and comorbidities on the risk of psychosis in Alzheimer disease.
AB  - OBJECTIVE: The objective of this study was to investigate the cumulative effect
      of the genes likely involved in Alzheimer disease (AD)-related psychosis and
      their interaction with disease stage and environmental factors. METHODS: Two
      hundred thirty-four patients with AD underwent clinical and neuropsychologic
      examination, behavioral and psychiatric disturbances evaluation, and were
      subsequently divided into two subgroups according to the presence (AD-P) or the
      absence (AD-nP) of psychotic symptoms. Cathecol-O-methyltransferase (COMT),
      serotonin gene-linked promoter region (5-HTTLPR), and Apolipoprotein E (ApoE)
      genotypes were performed. RESULTS: COMT*H (H/H or H/liter; odds ratio [OR]: 2.4;
      95% confidence interval [CI]: 1.13-5.11) and 5-HTTLPR*S (S/S or S/liter, OR:
      2.14; 95% CI: 1.13-4.07) were associated with AD-P. A gene dose effect was
      observed; in fact, carriers of both polymorphisms showed a fivefold risk for
      psychosis compared with patients bearing no polymorphisms. An interaction between
      these two genetic variations with disease stage and ischemic cardiomyopathy was
      found, the latter influencing AD-P risk only if "at-risk" genetic polymorphisms
      were present. The combined trend effect of COMT*H plus 5-HTTLPR*S and advance
      disease stage on AD-P risk was approximately 200% greater than that predicted by
      assuming additive effects, whereas the one obtained by COMT*H plus 5-HTTLPR*S and
      ischemic cardiomyopathy was 50% greater. ApoE genotype did not influence AD-P
      risk. CONCLUSIONS: These findings claim for a synergic effect of COMT*H and 5
      HTTLPR*S polymorphisms on the risk of psychosis in AD and for their interaction
      with disease stage and ischemic cardiomyopathy. This study suggests that
      considering both the genetic background and the environmental correlates might
      provide new insight for understanding psychosis mechanisms related to AD.

PMID- 16582044
TI  - Prediction of psychosis onset in Alzheimer disease: The role of cognitive
      impairment, depressive symptoms, and further evidence for psychosis subtypes.
AB  - BACKGROUND: Psychotic symptoms in Alzheimer disease (AD+P) identify a heritable
      phenotype associated with more rapid cognitive decline. The authors have proposed
      that AD+P is itself a composite of a misidentification and a paranoid subtype
      with increased cognitive impairment restricted to the misidentification type.
      Most prior studies of the clinical correlates of AD+P have been limited, however,
      by the inclusion of prevalent cases. METHODS: Subjects with possible or probable
      AD or mild cognitive impairment (MCI) without psychosis at study entry were
      assessed at the time of initial presentation and then annually. Psychotic
      symptoms were assessed using the CERAD Behavioral Rating Scale. Survival analyses
      used Cox proportional hazard models with time-dependent covariates to examine the
      predictors of psychosis onset. RESULTS: A total of 288 subjects completed at
      least one follow-up examination. Mean duration of follow-up was 22.1 months. The
      incidence of psychosis was 0.19 per person-year. Cognitive impairment was
      associated with onset of psychosis, largely as a result of its association with
      onset of the misidentification, but not the paranoid, subtype. Including
      psychotropic medication use in the model revealed an association of
      antidepressant use with the onset of psychosis. This latter association appeared
      to arise from an underlying association between depression and the risk of
      psychosis onset rather than from antidepressant treatment. CONCLUSION: These
      findings are consistent with the hypothesis that the misidentification and the
      paranoid subtypes each define a more biologically homogeneous group than AD+P as
      a whole. Further exploration of the relationship between depressive symptoms and
      psychosis in patients with AD is warranted.

PMID- 16582045
TI  - A double-blind, placebo-controlled study of venlafaxine and fluoxetine in
      geriatric outpatients with major depression.
AB  - BACKGROUND: Despite the high prevalence of depression in elderly patients, few
      well-designed, placebo-controlled studies of antidepressants have been conducted
      in this population. This masked, placebo-controlled trial assessed the efficacy
      and safety of venlafaxine and fluoxetine in depressed patients older than 65
      years. METHOD: Three hundred patients were randomly assigned to treatment with
      venlafaxine immediate release ([IR]; N = 104), fluoxetine (N = 100), or placebo
      (N = 96) in an eight-week trial. Venlafaxine doses were titrated from 37.5 to 225
      mg per day and fluoxetine doses were titrated from 20 to 60 mg per day, as
      necessary, over 29 days. Efficacy variables included the 21-item Hamilton
      Depression Rating Scale (HAM-D21) total score, HAM-D21 depressed mood item score,
      scores on the Montgomery Asberg Depression Rating Scale (MADRS), Clinical Global
      Impression-Severity of Illness (CGI-S) and Improvement (CGI-I) scales, and rates
      of response (based on change from baseline HAM-D or MADRS score or CGI-I score)
      and remission (HAM-D17 < or =7). For the purposes of this report, efficacy
      analyses are focused on the HAM-D21 total score. Safety assessments included
      monitoring of adverse events (AEs), physical examinations, vital signs
      assessments, laboratory determinations, and electrocardiograms. RESULTS: In all
      three of the treatment groups, there was a significant reduction at week 8
      compared with the baseline HAM-D21 total score. However, there were no
      significant differences among the three treatment groups on the change in HAM
      D21, MADRS, or CGI scores from baseline to week 8. There was no statistically
      significant difference in the proportion of remitters at the last on-therapy
      visit. The incidence of individual AEs was higher in the venlafaxine group (27%)
      compared with patients taking fluoxetine (19%) or placebo (9%). CONCLUSION: In
      this study, there was no significant difference in efficacy among placebo,
      venlafaxine, and fluoxetine for the treatment of depression.

PMID- 16582046
TI  - Satisfaction with mental health services in older primary care patients.
AB  - OBJECTIVE: This study examines whether older adult primary care patients are
      satisfied with two intervention models designed to ameliorate their behavioral
      health problems. METHODS: A total of 1,052 primary care patients aged 65 and
      older with depression, anxiety, or at-risk drinking were randomly assigned to and
      participated in either integrated care (IC) or enhanced specialty referral (ESR)
      model and completed the Client Satisfaction Questionnaire (CSQ) administered at
      three-month follow-up assessment. RESULTS: Older adult patients' satisfaction
      with IC (mean: 3.4, standard deviation [SD]: 0.60) was significantly higher than
      that with ESR (mean: 3.2, SD: 0.78), but the absolute difference was modest.
      Regression results showed that patients who used the IC model, attended the
      treatment service twice or more, or showed clinical improvement were more likely
      to express greater satisfaction. Stigma toward mental illness was negatively
      associated with satisfaction with mental health services. CONCLUSIONS: Older
      adults are more likely to have greater satisfaction with mental health services
      integrated in primary care settings than through enhanced referrals to specialty
      mental health and substance abuse clinics.

PMID- 16582047
TI  - Cognitive-behavioral treatment for obsessive-compulsive disorder in an elderly
      male with concurrent medical constraints.

PMID- 16582048
TI  - Bipolar and depressive types of schizoaffective disorder in old age.

PMID- 16582049
TI  - Increased risk of attempted suicide among aging Holocaust survivors.

PMID- 16582050
TI  - Editorial by Ancoli-Israel and Alessi.

PMID- 16582052
TI  - Anticholinergics in dementia and other confounding problems.

PMID- 16582053
TI  - Psychiatric drug promotion and the politics of neo-liberalism.
AB  - The pharmaceutical industry has popularized the idea that many problems are
      caused by imbalances in brain chemicals. This message helps to further the aims
      of neo-liberal economic and social policies by breeding feelings of inadequacy
      and anxiety. These feelings in turn drive increasing consumption, encourage
      people to accept more pressured working conditions and inhibit social and
      political responses.

PMID- 16582054
TI  - Patient preference randomised controlled trials in mental health research.
AB  - The relationship between psychiatric patients'preferences for different
      treatments and the outcome of interventions is unclear, as the few relevant
      trials have tended to be underpowered. Strong patient preferences result in
      patients refusing to enter a trial. This leads to bias and limits
      generalisability, and the patient preference randomised controlled trial (RCT)
      design has been proposed as an alternative. Limitations and advantages of patient
      preference RCTs are discussed.

PMID- 16582055
TI  - Psychotherapy plus antidepressant for panic disorder with or without agoraphobia:
      systematic review.
AB  - BACKGROUND: Panic disorder can be treated with psychotherapy, pharmacotherapy or
      a combination of both. AIMS: To summarise the evidence concerning the short- and
      long-term benefits and adverse effects of a combination of psychotherapy and
      antidepressant treatment. METHOD: Meta-analyses and meta-regressions were
      undertaken using data from all relevant randomised controlled trials identified
      by a comprehensive literature search. The primary outcome was relative risk (RR)
      of response. RESULTS: We identified 23 randomised comparisons (21 trials
      involving a total of 1709 patients). In the acute-phase treatment, the combined
      therapy was superior to antidepressant pharmacotherapy (RR=1.24,95% CI1.02-1.52)
      or psychotherapy (RR=1.16,95% CI1.03-1.30). After termination of the acute-phase
      treatment, the combined therapy was more effective than pharmacotherapy alone
      (RR=1.61,95% CI1.23-2.11) and was as effective as psychotherapy (RR=0.96, 95% CI
      0.79-1.16). CONCLUSIONS: Either combined therapy or psychotherapy alone may be
      chosen as first-line treatment for panic disorder with or without agoraphobia,
      depending on the patient's preferences.

PMID- 16582057
TI  - What can we conclude from studies on psychotherapy in bipolar disorder? Invited
      commentary on...Cognitive-behavioural therapy for severe and recurrent bipolar
      disorders.
AB  - The study by Scott et al is at odds with other published studies. Their design of
      a mixed group of relatively well or acutely ill bipolar patients who may or may
      not be on medication leads to difficulties in interpreting the results. Important
      clinical decisions should not be based on a post hoc analysis with a
      retrospective variable.

PMID- 16582056
TI  - Cognitive-behavioural therapy for severe and recurrent bipolar disorders:
      randomised controlled trial.
AB  - BACKGROUND: Efficacy trials suggest that structured psychological therapies may
      significantly reduce recurrence rates of major mood episodes in individuals with
      bipolar disorders. AIMS: To compare the effectiveness of treatment as usual with
      an additional 22 sessions of cognitive-behavioural therapy (CBT). METHOD: We
      undertook a multicentre, pragmatic, randomised controlled treatment trial
      (n=253). Patients were assessed every 8 weeks for 18 months. RESULTS: More than
      half of the patients had a recurrence by 18 months, with no significant
      differences between groups (hazard ratio=1.05; 95% CI 0.74-1.50). Post hoc
      analysis demonstrated a significant interaction (P=0.04) such that adjunctive CBT
      was significantly more effective than treatment as usual in those with fewer than
      12 previous episodes, but less effective in those with more episodes.
      CONCLUSIONS: People with bipolar disorder and comparatively fewer previous mood
      episodes may benefit from CBT. However, such cases form the minority of those
      receiving mental healthcare.

PMID- 16582058
TI  - Cost-utility of brief psychological treatment for depression and anxiety.
AB  - BACKGROUND: The cost-utility of brief therapy compared with cognitive-behavioural
      therapy (CBT) and care as usual in the treatment of depression and anxiety has
      not yet been determined. AIMS: To assess the cost-utility of brief therapy
      compared with CBT and care as usual. METHOD: A pragmatic randomised controlled
      trial involving 702 patients was conducted at 7 Dutch mental healthcare centres
      (MHCs). Patients were interviewed at baseline and then every 3 months over a
      period of 1.5 years, during which time data were collected on direct costs,
      indirect costs and quality of life. RESULTS: The mean direct costs of treatment
      at the MHCs were significantly lower for brief therapy than for CBT and care as
      usual. However, after factoring in other healthcare costs and indirect costs, no
      significant differences between the treatment groups could be detected. We found
      no significant differences in quality-adjusted life-years between the groups.
      CONCLUSIONS: Cost-utility did not differ significantly between the three
      treatment groups.

PMID- 16582059
TI  - Cost-effectiveness of preventing depression in primary care patients: randomised
      trial.
AB  - BACKGROUND: Little is known about the cost-effectiveness of preventing mental
      disorders. AIMS: To study the cost-effectiveness of care as usual plus minimal
      contact psychotherapy relative to usual care alone in preventing depressive
      disorder. METHOD: An economic evaluation was conducted alongside a randomised
      clinical trial. Primary care patients with sub-threshold depression were assigned
      to minimal contact psychotherapy plus usual care (n=107) or to usual care alone
      (n=109). RESULTS: Primary care patients with sub-threshold depression benefited
      from minimal contact psychotherapy as it reduced the risk of developing a full
      blown depressive disorder from 18% to 12%. In addition, this intervention had a
      70% probability of being more cost-effective than usual care alone. A sensitivity
      analysis indicated the robustness of these results. CONCLUSIONS: Over 1 year
      adjunctive minimal contact psychotherapy improved outcomes and generated lower
      costs. This intervention is therefore superior to usual care alone in terms of
      cost-effectiveness.

PMID- 16582060
TI  - Cost-effectiveness and cost-utility of tricyclic antidepressants, selective
      serotonin reuptake inhibitors and lofepramine: randomised controlled trial.
AB  - BACKGROUND: The cost-effectiveness of tricyclic antidepressants (TCAs) and
      selective serotonin reuptake inhibitors (SSRIs) has not been compared in a
      prospective study in primary care. AIMS: To determine the relative cost
      effectiveness of TCAs, SSRIs and lofepramine in UK primary care. METHOD: An open
      label, three-arm randomised trial with a preference arm. Practitioners referred
      327 patients with incident depression. RESULTS: No significant differences were
      found in effectiveness or cost-effectiveness. The numbers of depression-free
      weeks over 12 months (on the Hospital Anxiety and Depression Scale) were 25.3
      (95% CI 21.3-29.0) for TCAs, 28.3 (95% CI 24.3-32.2) for SSRIs and 24.6 (95% CI
      20.6-28.9) for lofepramine. Mean health service costs per patient were pound 762
      (95% CI 553-1059) for TCAs, pound 875 (95% CI 675-1355) for SSRIs and pound 867
      (95% CI 634-1521) for lofepramine. Cost-effectiveness acceptability curves
      suggested SSRIs were most cost-effective (with a probability of up to 0.6).
      CONCLUSIONS: The findings support a policy of recommending SSRIs as first-choice
      antidepressants in primary care.

PMID- 16582061
TI  - Duloxetine in the prevention of relapse of major depressive disorder: double
      blind placebo-controlled study.
AB  - BACKGROUND: Relapse rates may be as high as 50% in people with major depressive
      disorder (MDD) previously treated to remission. AIMS: Duloxetine, an inhibitor of
      serotonin and noradrenaline reuptake that is licensed in Europe, the USA and
      elsewhere for the treatment of depressive episodes, was evaluated with regard to
      its efficacy, safety and tolerability in the prevention of relapse of MDD.
      METHOD: Adult out-patients with MDD received duloxetine (60 mg daily) for 12
      weeks (n=533). Patients who responded to the drug were then randomised to
      duloxetine(60 mg daily)(n=136) or or placebo placebo (n=142) for 26 weeks. The
      primary measure of efficacy was time to relapse. RESULTS: Patients who received
      duloxetine (60 mg daily) experienced significantly longer times to relapse of
      MDD, and better efficacy, global well-being, and quality-of-life outcomes
      compared with patients who received placebo. It should be noted that adverse
      events which occur in discontinuation may mimic some signs of depressive relapse,
      and were not specifically elicited in this study. CONCLUSIONS: Duloxetine (60 mg
      daily) is effective in the prevention of relapse of MDD during continuation
      treatment.

PMID- 16582062
TI  - Relationship between antidepressant sales and secular trends in suicide rates in
      the Nordic countries.
AB  - BACKGROUND: The effect of recent increases in antidepressant prescribing on
      population suicide rates is uncertain. AIMS: To investigate the relationship
      between antidepressant sales and trends in suicide rates. METHOD: Graphical and
      quantitative assessment of trends in suicide and antidepressant sales in Norway,
      Sweden, Denmark and Finland. RESULTS: Suicide rates declined in all four
      countries during the 1990 s, whereas antidepressant sales increased by 3- to 4
      fold. Decreasing suicide rates in Sweden and Denmark preceded the rise in
      antidepressant sales by over 10 years, although the reductions accelerated
      between 1988 and 1990. In Norway, a modest but short-lived decline in suicide
      rates began around the time of the increase in antidepressant sales. In Finland,
      decreases in male suicide rates and to a lesser extent in female suicide rates
      began around the time of increased antidepressant sales. In all four countries
      decreases in suicide rates appeared to precede the widespread use of SSRIs.
      CONCLUSIONS: We found mixed evidence that increases in antidepressant sales have
      coincided with a reduction in the number of suicides in Nordic countries.

PMID- 16582063
TI  - Depressive symptoms in urban population samples in Russia, Poland and the Czech
      Republic.
AB  - BACKGROUND: Relatively little is known about depression in countries that were
      formerly part of the Soviet Union, especially Russia. AIMS: To investigate the
      rates and distribution of depressive symptoms in urban population samples in
      Russia, Poland and the Czech Republic. METHOD: A cross-sectional study was
      conducted in randomly selected men and women aged 45-64 years (n=2151 in total,
      response rate 69%) in Novosibirsk (Russia), Krakow (Poland) and Karvina (Czech
      Republic). The point prevalence of depressive symptoms in the past week was
      defined as a score of at least 16 on the Center for Epidemiological Studies
      Depression scale. RESULTS: In men the prevalence of depressive symptoms was 23%
      in Russia, 21% in Poland and 19% in the Czech Republic; in women the rates were
      44%, 40% and 34% respectively. Depressive symptoms were positively associated
      with material deprivation, being unmarried and binge drinking. The association
      between education and depression was inverse in Poland and the Czech Republic but
      positive in Russia. CONCLUSIONS: The prevalence of depressive symptoms in these
      eastern European urban populations was relatively high; as in other countries, it
      was associated with alcohol and several sociodemographic factors.

PMID- 16582064
TI  - Neuropsychological dysfunction, soft neurological signs and social disability in
      euthymic patients with bipolar disorder.
AB  - BACKGROUND: Neurocognitive deficits exist in euthymic patients with bipolar
      disorder, but relationships between symptoms, psychosocial and neurological
      factors remain uncertain. AIMS: To measure neurocognitive function in bipolar
      disorder and explore links to sub-syndromal mood symptoms, soft neurological
      signs and psychosocial impairment. METHOD: Attention, memory and executive
      function were tested in 37 euthymic patients with bipolar disorder and 37
      controls. Psychosocial functioning, soft neurological signs and residual mood
      symptoms were assessed. RESULTS: Performances on tests reflecting executive
      function and verbal memory (but not attention) were significantly poorer in the
      bipolar disorder group. Sub-syndromal mood symptoms produced small cognitive
      effects, predominantly on verbal memory. Soft neurological signs, especially
      frontal signs, were marked; some patients showed marked social disability which
      correlated strongly with soft neurological signs but weakly with executive
      dysfunction, which was linked to illness episodes. CONCLUSIONS: Cognitive
      dysfunction, social dysfunction and soft signs occur in euthymic patients with
      bipolar disorder and may represent trait deficits.

PMID- 16582065
TI  - Personality and substance use disorders in young adults.
AB  - BACKGROUND: There have been no studies of the co-occurrence of personality and
      substance use disorders in young community-dwelling adults. AIMS: To examine the
      association between DSM-IV personality disorders and substance use disorders in a
      large representative sample of young community-dwelling participants. METHOD:
      Young Australian adults (n=1520, mean age=24.1 years) were interviewed to
      determine the prevalence of substance use disorders; 1145 also had an assessment
      for personality disorder. RESULTS: The prevalence of personality disorder was
      18.6% (95% CI 16.5-20.7). Personality disorder was associated with indices of
      social disadvantage and the likely presence of common mental disorders.
      Independent associations were found between cluster B personality disorders and
      substance use disorders. There was little evidence for strong confounding or
      mediating effects of these associations. CONCLUSIONS: In young adults, there are
      independent associations between cluster B personality disorders and substance
      use disorders.

PMID- 16582066
TI  - Ethnic differences among patients in high-security psychiatric hospitals in
      England.
AB  - BACKGROUND: Black (Black Caribbean and Black African) patients are over
      represented in admissions to general adult and medium-security psychiatric
      services in England. AIMS: To describe the sociodemographic, clinical and offence
      characteristics of patients in high-security psychiatric hospitals (HSPHs) in
      England, and to compare admission rates and unmet needs by ethnic group. METHOD:
      A total of 1255 in-patients were interviewed, and their legal status, socio
      demographic characteristics and individual treatment needs were assessed.
      RESULTS: Black patients in HSPHs are over-represented by 8.2 times (range 3.2
      24.4,95% CI 7.1-9.3), are more often male (P=0.037), and are more often diagnosed
      with a mental illness and less often diagnosed with a personality disorder or
      learning disability (P<0.001) than White patients. Unmet needs were significantly
      less common among White than among Black patients (mean values of 2.22 v. 2.62,
      difference=0.40,95% CI 0.06-0.73). CONCLUSIONS: Compared with the proportion of
      Black patients in the general population in their region of origin, a much higher
      proportion of Black patients were admitted to HSPHs, and fewer of their needs
      were met.

PMID- 16582067
TI  - Emergency psychiatry, compulsory admissions and clinical presentation among
      immigrants to the Netherlands.
AB  - BACKGROUND: Black individuals in the UK have higher rates of contact with
      psychiatric emergency services than their White counterparts. It is unknown
      whether this is also the case in other European countries. AIMS: To compare the
      risk of contact with psychiatric emergency services and of compulsory admission
      between immigrant groups to The Netherlands and Dutch natives, and to determine
      the unique contribution of ethnicity to compulsory admission. METHOD: Study of
      720 people referred to emergency psychiatric services in Greater Rotterdam, The
      Netherlands. RESULTS: The relative risks (RRs) for contacts with psychiatric
      emergency services, for having a psychotic disorder and for compulsory admission
      were significantly higher in most immigrant groups. Moroccans, Surinamese and
      Dutch Antilleans had the highest risks of compulsory admission. After controlling
      for symptom severity, danger, motivation for treatment and level of social
      functioning, non-Western origin was no longer associated with compulsory
      admission. CONCLUSIONS: Non-Western immigrant groups were overrepresented in
      psychiatric emergency care and were admitted compulsorily more frequently,
      possibly owing to a different clinical presentation.

PMID- 16582068
TI  - The Kraepelinian dichotomy.

PMID- 16582069
TI  - Social defeat and schizophrenia.

PMID- 16582070
TI  - Social defeat and schizophrenia.

PMID- 16582071
TI  - Post-traumatic stress disorder after life events.

PMID- 16582072
TI  - Schizophrenia, cancer and imprinting: early nutritional influences.

PMID- 16582073
TI  - Psychiatric comorbidity and chronic fatigue syndrome.

PMID- 16582074
TI  - Not all women fancy single-sex wards.

PMID- 16582075
TI  - Not all women fancy single-sex wards.

PMID- 16582076
TI  - Spectrum and clinical implications of syntaxin 11 gene mutations in familial
      haemophagocytic lymphohistiocytosis: association with disease-free remissions and
      haematopoietic malignancies.
AB  - OBJECTIVE: To determine the frequency and spectrum of mutations in the gene
      encoding syntaxin 11 (STX11) in familial haemophagocytic lymphohistiocytosis
      (FHL), a rare autosomal recessive disorder of immune dysregulation characterised
      by a defect in natural killer cell function. METHODS: Mutational analysis of
      STX11 by direct sequencing was done in 28 FHL families that did not harbour
      perforin mutations, previously identified in some FHL patients. A detailed
      investigation of clinical features of these patients was also undertaken.
      RESULTS: Two different STX11 mutations were identified, one nonsense mutation and
      one deletion, affecting six of 34 children in four of 28 unrelated PRF1 negative
      families. Both mutations have been reported before. Three patients experienced
      long periods (> or = 1 year) in remission without specific treatment, which is
      very uncommon in this disease. Despite the milder phenotype, some children with
      STX11 mutations developed severe psychomotor retardation. Two of the six patients
      harbouring STX11 gene defects developed myelodysplastic syndrome (MDS) or acute
      myelogenous leukaemia (AML). CONCLUSIONS: STX11 gene mutations were found in 14%
      of the PRF1 negative FHL families included in the present cohort. These results
      suggest that STX11 gene mutations may be associated with secondary malignancies
      (MDS/AML), and that there is segregation of specific clinical features in FHL
      patients with an underlying genotype.

PMID- 16582077
TI  - Exonic STK11 deletions are not a rare cause of Peutz-Jeghers syndrome.
AB  - BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant cancer
      predisposition syndrome characterised by oro-facial pigmentation and
      hamartomatous polyposis of the gastrointestinal tract. A causal germline mutation
      in STK11 can be identified in 30% to 80% of PJS patients. METHODS: Here we report
      the comprehensive mutational analysis of STK11 in 38 PJS probands applying
      conventional PCR based mutation detection methods and the recently introduced
      MLPA (multiplex ligation dependent probe amplification) technique developed for
      the identification of exonic deletions/duplications. RESULTS: Nineteen of 38
      probands (50%) had detectable point mutations or small scale deletions/insertions
      and six probands (16%) had genomic deletions encompassing one or more STK11
      exons. CONCLUSIONS: These findings demonstrate that exonic STK11 deletions are a
      common cause of PJS and provide a strong rationale for conducting a primary
      screen for such mutations in patients.

PMID- 16582078
TI  - Influence of glutathione-S-transferase (GSTM1, GSTP1, GSTT1) and cytochrome p450
      (CYP1A1, CYP2D6) polymorphisms on numbers of basal cell carcinomas (BCCs) in
      families with the naevoid basal cell carcinoma syndrome.
AB  - BACKGROUND: The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal
      dominant multisystem disorder with variable expression. NBCCS patients have
      variable susceptibility to development of basal cell carcinoma (BCC). Previous
      studies have shown that polymorphisms of some metabolic genes encoding the
      cytochrome p450 (CYP) and glutathione-S-transferase (GST) enzymes influenced the
      numbers of BCCs in sporadic BCC cases. OBJECTIVE: To determine whether allelic
      variants of these genes contribute to the variation in numbers of BCCs observed
      in NBCCS families. METHODS: Genotyping and analysis was carried out in 152
      members (69 affected and 83 unaffected) of 13 families with NBCCS for seven
      polymorphisms in five metabolic genes including CYP1A1, CYP2D6, GSTM1, GSTP1, and
      GSTT1. RESULTS: GSTP1 Val105 and GSTP1 Val114 alleles were significantly
      associated with fewer BCC numbers (odds ratio (OR)105 = 0.55 (95% confidence
      interval, 0.35 to 0.88); OR114 = 0.20 (0.05 to 0.88)). The Val(105) allele showed
      a dose dependent effect (OR(Ile/Val) = 0.58 (0.34 to 0.88); OR(Val/Val) = 0.34
      (0.14 to 0.78)). In addition, fewer jaw cysts were observed in carriers of the
      three p450 polymorphisms (CYP1A1m1, CYP1A1m2, and CYP2D6*4) (OR(CYP1A1m1) = 0.27
      (0.12 to 0.58); OR(CYP1A1m2) = 0.25 (0.08 to 0.78); OR(CYP2D6*4) = 0.33 (0.18 to
      0.60)). CONCLUSIONS: Genetic variants might contribute to the variation in
      numbers of BCCs and jaw cysts observed in NBCCS families.

PMID- 16582079
TI  - Association of susceptibility to the development of pneumonia in the older
      Japanese population with haem oxygenase-1 gene promoter polymorphism.
AB  - BACKGROUND: Oxidative stresses including cigarette smoking are implicated in the
      pathogenesis of cerebrovascular diseases, which are associated with pneumonia
      because of frequent aspiration. Haem oxygenase-1 (HO-1) acts in cytoprotection
      against oxidants, provides anti-inflammatory effects, and inhibits atherogenesis.
      A (GT)(n) dinucleotide repeat in the human HO-1 promoter modulates HO-1 gene
      expression and shows length polymorphism, which is grouped into three classes:
      class S (<27 repeats), class M (> or = 27, <33 repeats), and class L (> or = 33
      repeats) alleles. OBJECTIVE: To investigate the correlation between the HO-1 gene
      polymorphism and development of pneumonia in elderly Japanese. METHODS: The
      length of the (GT)n repeats was analysed in 200 elderly patients with pneumonia
      and 200 control subjects. The association of the HO-1 gene polymorphism with risk
      of pneumonia was estimated by logistic regression. RESULTS: The proportion of
      allele frequencies in class L, and the proportion of genotypic frequencies in the
      L-allele carriers (L/L, L/M, and L/S), was significantly higher in patients with
      pneumonia than in controls (20% v 10% in class L, and 34% v 18% in L-allele
      carriers). After adjustment for potentially confounding factors, both
      cerebrovascular disorders and HO-1 gene L-allele carriers were significant and
      independent risk factors for pneumonia. The adjusted odds ratio for L-allele
      carriers v non-L-allele carrier was 2.1 (95% confidence interval, 1.2 to 3.6).
      CONCLUSIONS: The large size of a (GT)n repeat in the HO-1 gene promoter may be
      associated with susceptibility to pneumonia in the older Japanese population.

PMID- 16582080
TI  - Use of gene expression microarrays for evaluating environmental stress tolerance
      at the cellular level in cattle.
AB  - Selecting domestic animals for tolerance to thermal stress (TS) has been
      counterproductive, because acclimation involves reducing or diverting
      metabolizable energy from production to balance heat gain and loss. Ideally,
      simultaneous selection for increased production and improved thermotolerance is
      desirable, but to accomplish this at the genomic level the genes associated with
      acclimation, adaptation, and thermo-tolerance need to be identified. We evaluated
      the effects of TS on mammary development and gene expression in vitro using a
      bovine mammary epithelial cell collagen gel culture system. Acute TS was
      characterized by inhibition and regression of the ductal branches. Gene
      expression profiling revealed an overall upregulation of genes associated with
      the stress response and protein repair. In contrast, genes associated with
      cellular and mammary epithelial cell-specific biosynthesis, metabolism, and
      morphogenesis were generally downregulated by TS. Future studies will examine the
      impact of acclimation and adaptation on gene expression to identify those genes
      associated with acquisition of thermal tolerance.

PMID- 16582081
TI  - The biological basis for prenatal programming of postnatal performance in pigs.
AB  - The main purpose of this review is to discuss associations between within-litter
      variation in birth weight, and preweaning survival and postnatal growth in the
      pig, as the basis for suggesting that the developmental competence of pigs born,
      as well as the size of the litter, need critical consideration. Extremes of
      intrauterine growth retardation (IUGR) occur within a discrete subset of fetuses,
      substantially smaller than their littermates and commonly described as runt
      piglets. The lower preweaning growth of runt pigs cannot be entirely explained
      based on their lower birth weight, nor do they show full postnatal compensatory
      growth. Interestingly, this more complex reprogramming of development in runt
      pigs can already be identified by d 27 to 35 of gestation. Recently, we reported
      more universal IUGR effects in commercial dam-line sows, as an indirect response
      to selection for increased litter size. High ovulation rates (>30 ovulations) in
      a proportion of greater parity sows are associated with increased numbers of
      conceptuses surviving to d 30 of gestation, resulting in detrimental effects on
      placental development of uterine crowding in the early postimplantation period.
      In turn, this limits nutrient availability to the embryo during a critical period
      of myogenesis. Consequently, although a reduction in the number of conceptuses
      occurs by d 50, placental development in the surviving fetuses remains
      compromised, resulting in IUGR and reduced numbers of muscle fibers at d 90 and
      at birth, in all surviving littermates. These effects of uterine crowding on
      fetal and postnatal development are analogous to the detrimental effects of
      nutritional restriction in gestating sows on fetal myogenesis, birth weight, and
      postnatal growth. The incompatibility between increased numbers of conceptuses
      surviving to the postimplantation period, in the absence of increased uterine
      capacity, offers a biological explanation for increased variability in birth
      weight and postnatal growth performance reported in greater parity sows. We
      conclude that a strategy of introducing hyperprolific females into the breeding
      nucleus, as a means of increasing the numbers of pigs born, needs to be
      critically evaluated in the context of the overall efficiency of pork production.

PMID- 16582083
TI  - Immunological aspects of nematode parasite control in sheep.
AB  - Gastrointestinal nematode parasitism is arguably the most serious constraint
      affecting sheep production worldwide. Economic losses are caused by decreased
      production, the costs of prophylaxis and treatment, and the death of the infected
      animals. The nematode of particular concern is Haemonchus contortus, which can
      cause severe blood loss resulting in anemia, anorexia, depression, loss of
      condition, and eventual death. The control of nematode parasites traditionally
      relies on anthelmintic treatment. The evolution of anthelmintic resistance in
      nematode populations threatens the success of drug treatment programs.
      Alternative strategies for control of nematode infections are being developed,
      and one approach is to take advantage of the host's natural or acquired immune
      responses, which can be used in selection programs to increase the level of
      resistance in the population. Vaccination can also be used to stimulate or boost
      the host's acquired immunity. The induction of protective resistance is dependent
      on the pattern of cytokine gene expression induced during infection by two
      defined CD4+ T-helper cell subsets, which have been designated as Th1 or Th2.
      Intracellular parasites most often invoke a Th1-type response, and helminth
      parasites a Th2-type response. Breeds of sheep resistant to infection have
      developed resistance over a much longer term of host-parasite relationship than
      genetically selected resistant lines. The immune components involved in these
      different responses and types of host-parasite relationships will be reviewed.
      The potential for using vaccines has been investigated, with variable results,
      for several decades. The few successes and potential new antigen candidates will
      also be reviewed.

PMID- 16582082
TI  - Consequences of birth weight for postnatal growth performance and carcass quality
      in pigs as related to myogenesis.
AB  - In polytocous species such as the pig there is intralitter variation in birth
      weight and skeletal muscle fiber number. It is commonly recognized that low birth
      weight in piglets correlates with decreased survival and lower postnatal growth
      rates. In the majority of low birth weight piglets low numbers of muscle fibers
      differentiate during prenatal myogenesis, for genetic or maternal reasons, and
      those low birth weight piglets with reduced fiber numbers are unable to exhibit
      postnatal catch-up growth. Pigs of low birth weight show the lowest growth
      performance and the lowest lean percentage at slaughter. In addition, they tend
      to develop extremely large muscle fibers (giant fibers) and poor meat quality,
      which results in part from the inverse correlation between fiber number and fiber
      size. Prenatal growth and myogenesis are under the control of various genetic and
      environmental factors, which can be targeted for growth manipulation. Genetic
      selection is considered a suitable tool to improve fetal growth and myogenesis.
      Prenatal development is mainly dependent on a close interrelation between
      nutritional supply/use and regulation by hormones and growth factors. In
      particular, the maternal somatotropic axis plays a significant role in the
      control of myogenesis. Thus, treatment of sows with GH until mid-gestation was
      able to increase birth weight and the number of muscle fibers in the small
      littermates of the progeny that are disadvantaged by insufficient nutrient
      supply. Growth hormone treatment was associated with increased nutrient
      availability to the embryos and changes in regulatory proteins of the GH-IGF
      axis. Interactions between maternal nutrition and the somatotropic axis in
      determining prenatal growth and myogenesis are worthy of further investigation.

PMID- 16582085
TI  - Sites, rates, and limits of starch digestion and glucose metabolism in growing
      cattle.
AB  - Growing cattle in the United States consume up to 6 kg of starch daily, mainly
      from corn or sorghum grain. Total tract apparent digestibility of starch usually
      ranges from 90 to 100% of starch intake. Ruminal starch digestion ranges from 75
      to 80% of starch intake and is not greatly affected by intake over a range of 1
      to 5 kg of starch/d. Starch apparently digested in the small intestine decreases
      from 80 to 34% as starch entering the small intestine increases from 0.2 to 2
      kg/d. Starch apparently digested in the large intestine ranges from 44 to 46% of
      starch entering the large intestine. Approximately 70% of starch digested in the
      small intestine appears as glucose in the bloodstream. Within the range of starch
      intakes that do not cause rumen upsets, increasing starch (and energy) intake
      increases the amount of starch digested in the rumen, increases the supply of
      starch to the small intestine, increases starch digested in small intestine
      (albeit at reduced efficiency), and increases starch digested in the large
      intestine, such that total tract digestibility remains relatively constant. With
      increased starch intake, most of the starch is still digested in the rumen, but
      increasing amounts of starch escape ruminal and intestinal digestion, and
      disappear distal to the ileocecal junction. Again, within the range of starch
      intakes that do not cause rumen upsets, as starch intake increases, hepatic
      gluconeogenesis increases, glucose entry increases, and glucose irreversible loss
      increases, with a significant portion lost as CO2. The ability to increase use of
      dietary starch to support greater weight gains or improved marbling could come
      from increasing starch digestion in a healthy rumen or in the small intestine,
      but we conclude that the main limit to use of dietary starch to support live
      weight gain is digestion and absorption from the small intestine. Increased
      oxidation of glucose at greater starch intakes may alter energetic efficiency by
      sparing other oxidizable substrates, like amino acids.

PMID- 16582084
TI  - Biological control of nematode parasites in sheep.
AB  - In a world in which sheep producers are facing increasing problems due to the
      rapid spread of anthelmintic resistance, the battle against gastrointestinal
      parasitic nematodes is a difficult one. One of the potential new tools for
      integrated control strategies is biological control by means of the nematode
      destroying microfungus Duddingtonia flagrans. This fungus forms sticky traps that
      catch developing larval stages of parasitic nematodes in the fecal environment.
      When resting spores (chlamydospores) of this fungus are fed daily to grazing
      animals for a period of time, the pasture infectivity and thus, the worm burden
      of grazing animals are lowered, especially in young lambs. Research has been
      conducted throughout the world covering many different climates and management
      systems. An Australian parasite model showed that if the fungus performs
      efficiently (> or =90% reduction in worm burden) for 2 or 3 mo, it should
      contribute significantly to a reduction in the number of dead lambs otherwise
      occurring when managed only by anthelmintic treatment and grazing management.
      Feeding or field trials have clearly demonstrated that dosing with a few hundred
      thousand spores per kilogram of live BW not only reduced the number of infective
      larvae but also increased the BW of the lambs compared with controls not given
      fungus. Initial Australian work with feeding spores by means of a block
      formulation or a slow-release device has shown some promise, but further work is
      needed to fully develop these delivery systems. In tropical Malaysia, small
      paddock trials and field studies resulted in significant improvements, in terms
      of lower worm burdens and increased live BW, when feeding half a million spores
      daily to grazing lambs. Additional benefits have been observed when the fungus is
      employed in combination with a fast rotational grazing system. Research has also
      demonstrated that spores can be delivered in slightly moist feed block material,
      but only if such blocks are consumed rapidly, because of their very short shelf
      life. In the northern, temperate Danish climate it has been demonstrated that
      daily feeding of half a million spores per kilogram of live BW can lead to
      significant production benefits, with increased live BW gain in fungus-exposed
      animals. Biological control of parasitic nematodes in sheep seems to hold promise
      for the future, but to be able to assist producers, the optimal delivery system
      needs to be refined and further developed. In addition, more work will be needed
      to define the best use of this technology in different geographic regions.

PMID- 16582086
TI  - Adipocytes, myofibers, and cytokine biology: new horizons in the regulation of
      growth and body composition.
AB  - Muscle growth in meat animals is a complex process governed by integrated signals
      emanating from multiple endocrine and immune cells. A generalized phenomenon
      among meat animal industries is that animals commonly fail to meet their genetic
      potential for growth in commercial production settings. Therefore, understanding
      the impact of stress and disease on muscle growth is essential to improving
      production efficiency. The adipocyte in particular seems to be well positioned as
      an interface between energy status and immune function, and may thus influence
      nutrient partitioning and growth through a combination of signals that influence
      fat metabolism, glucose uptake, and insulin sensitivity. Adipocytes and myofibers
      are active participants in the innate immune response, and as such, produce a
      number of metabolic regulators, including leptin, adiponectin, and
      proinflammatory cytokines. Specifically, adipocytes and muscle cells respond
      directly to bacterial lipopolysaccharide (LPS) by producing interleukin-6 (IL-6)
      and tumor necrosis factor-alpha (TNFalpha). However, adipocytes are also the
      predominant source of the antiinflammatory hormone adiponectin, which regulates
      the nuclear factor kappa-B transcription factor. The ability to recognize
      antigens and produce regulatory molecules strategically positions adipocytes and
      myofibers to regulate growth locally, and to reciprocally regulate metabolism
      peripherally.

PMID- 16582087
TI  - Gene expression profiling: insights into skeletal muscle growth and development.
AB  - Microarray technology is now available for many livestock species, and animal
      scientists are beginning to utilize the technology to address issues of
      importance to animal agriculture. This review discusses how microarray technology
      has been applied to study global gene expression changes in skeletal muscle. For
      example, microarrays have been used to elucidate gene function in knockout mice,
      evaluate breed differences, evaluate the effects of hormone administration, and
      evaluate the effects of diet. Data generated from these global gene expression
      studies are providing new insights to stimulate future hypothesis-driven
      research.

PMID- 16582088
TI  - Estimation of nutrient requirements using broken-line regression analysis.
AB  - We evaluated and compared various broken-line regression models and SAS (SAS
      Inst. Inc., Cary, NC) procedures for estimating nutrient requirements from
      nutrient dose response data. We used the SAS (Version 9) procedures NLIN and
      NLMixed and the response data of Parr et al. (2003), who evaluated the isoleucine
      requirement of growing swine. The SAS NLIN was used to fit 2 different broken
      line regression models: a simple 2 straight-line, one-breakpoint model and a
      quadratic broken-line model in which the response below the single breakpoint was
      quadratic; there was a plateau above the breakpoint. The latter was fit using 2
      different approaches in NLIN. We also used SAS NLMixed to fit 3 different broken
      line models: the 2 straight-line, one-breakpoint model that included a random
      component for the plateau; the quadratic broken-line model that included a random
      component for the plateau; and the quadratic broken-line model that included
      random components for both the plateau and the slope of the curve below the
      requirement. The best fit (greater adjusted R2; least log likelihood) was
      achieved using SAS NLMixed and the quadratic model with a random component for
      asymptote included in the model. Model descriptions, SAS code, and output are
      presented and discussed. Additionally, we provide other examples of possible
      models and discuss approaches to handling difficult-to-fit data.

PMID- 16582089
TI  - Selection for sow longevity.
AB  - Sow longevity plays an important role in economically efficient piglet production
      because sow longevity is related to the number of piglets produced during its
      productive lifetime; however, selection for sow longevity is not commonly
      practiced in any pig breeding program. There is relatively little scientific
      literature concerning the genetic parameters (genetic variation and genetic
      correlations) or methods available for breeding value estimation for effective
      selection for sow longevity. This paper summarizes the current knowledge about
      the genetics of sow longevity and discusses the available breeding value
      estimation methods for sow longevity traits. The studies in the literature
      clearly indicate that sow longevity is a complex trait, and even the definition
      of sow longevity is variable depending on the researcher and research objective.
      In general, the measures and analyses of sow longevity can be divided into 1)
      continuous traits (e.g., productive lifetime) analyzed with proportional hazard
      models; and 2) more simple binary traits such as stayability until some
      predetermined fixed parity. Most studies have concluded that sufficient genetic
      variation exists for effective selection on sow longevity, and heritability
      estimates have ranged between 0.02 and 0.25. Moreover, sow longevity has shown to
      be genetically associated with prolificacy and leg conformation traits. Variable
      results from previous research have led to a lack of consensus among swine
      breeders concerning the valid methodology of estimating breeding values for
      longevity traits. One can not deny the superiority of survival analysis in the
      modeling approach of longevity data; however, multiple-trait analyses are not
      possible using currently available survival analysis software. Less sophisticated
      approaches have the advantage of evaluating multiple traits simultaneously, and
      thus, can use the genetic associations between sow longevity and other traits.
      Additional research is needed to identify the most efficient selection methods
      for sow longevity. Future research needs to concentrate on multiple trait
      analysis of sow longevity traits. Moreover, because longevity is a fitness trait,
      the nonadditive genetic effects (e.g., dominance) may play important role in the
      inheritance of sow longevity. Currently, not a single estimate for dominance
      variance of sow longevity could be identified from the scientific literature.

PMID- 16582090
TI  - Adaptation of beef cattle to high-concentrate diets: performance and ruminal
      metabolism.
AB  - The diet adaptation period is widely considered a critical period of time in
      which nutritional management practices can promote or impair subsequent
      performance and health. Performance studies indicate that adapting feedlot cattle
      with incremental increases in dietary concentrate, from approximately 55 to 90%
      of diet DM, in 14 d or less, while allowing ad libitum access to the diet,
      generally results in reduced performance during adaptation or over the entire
      feeding period. However, the number of cattle involved in these studies does not
      allow insight into the frequencies of metabolic disorders associated with the
      management practices tested. Adapting cattle by restricting the quantity of
      higher-concentrate diets offered shows promise for improving production
      efficiency, but further development is needed for application in commercial
      feedlots. Evidence suggests considerable diversity in the ability of animals to
      cope with ingested cereal grain, and indicates that diet adaptation procedures
      should affect the frequency of health-impaired or low-performing cattle in a pen.
      Individuals that seem to effectively regulate voluntary feed intake during
      adaptation generally display a steady increase in DMI as dietary concentrate is
      increased. These data also highlight a seemingly counterproductive, repeating
      cycle of overconsumption, followed by a pronounced reduction in ruminal pH, by
      cattle that appear to cope less favorably with grain adaptation. At least a
      portion of this diversity may relate to the maintenance of protozoal populations.
      Increases in amylolytic bacteria seemed to follow the increment of additional
      concentrate. Protozoa were most numerous when the diet contained approximately
      60% concentrate, and lactate-utilizing bacteria increased more markedly when the
      diet contained more than approximately 70% concentrate. Available in vivo data
      suggest that the number of lactate-utilizing bacteria may reach a plateau for a
      given diet composition after 2 to 7 d, but thorough assessments of the time
      course of events using modern techniques are lacking. Further research is needed
      to characterize how the quantity and frequency of increases in cereal grain
      consumption, reflective of industry practices, impact microbial dynamics, and to
      identify the biological features that allow certain animals to adapt more readily
      to high-concentrate diets.

PMID- 16582091
TI  - An upper limit for caloric density of finishing diets.
AB  - This review assessed the relationships between dietary energy density and animal
      performance in an effort to evaluate a possible upper limit for energy density in
      finishing diets for cattle. Data were combined from 49 experiments (69 trials;
      243 treatment observations) in which the dietary ME concentration (Mcal/kg of DM)
      was varied by level of concentrate, grain source, grain processing, and level of
      supplemental fat. Dietary concentrations of ME were determined using 1) NRC
      values of ME from diet ingredients; or 2) values derived from the literature, in
      which ingredient ME had been calculated from animal performance. Procedures for
      pooling data from multiple studies were used. The dependent variable was fit to a
      model that included a random slope and intercept clustered by trial. Trial
      adjusted dependent variables (animal performance and carcass characteristics)
      were regressed on the independent variable (dietary ME concentration). Models
      were fit to cubic equations, and then reduced from cubic to quadratic to linear
      equations when the cubic and quadratic terms were not significant at P > 0.10.
      When NRC values were used, the relationship of DMI (% of BW) to dietary ME was
      linear (DMI decreased as ME increased; R2 = 0.631). However, the slope of ME
      intake (Mcal/kg of BW(0.75)) vs. dietary ME content did not differ (P > 0.25)
      from zero, supporting the concept that ruminants on high-grain diets (2.7 to 3.3
      Mcal of ME/kg of DM) eat to maintain constant energy intake. Quadratic
      relationships were observed (P < 0.05) when ADG and G:F vs. dietary ME
      concentration were analyzed. Gain:feed was maximized with 3.46 (NRC) to 3.65
      (calculated) Mcal/kg of ME from the total diet, 2.99 (NRC) to 3.40 (calculated)
      Mcal/kg of ME from grain, and 0.43 (NRC) to 0.53 (calculated) Mcal/kg of ME from
      supplemental fat. Most relationships of carcass traits to dietary ME were not
      significant (P > 0.10). Increased 12th-rib fat at greater ME and increasing KPH
      suggests greater fat deposition with increasing caloric density. Assuming that
      NRC ME values for ingredients commonly used in finishing diets are correct, the
      upper caloric limit for maximizing ADG and G:F was 3.16 and 3.45 Mcal/kg of DM,
      respectively. Reaching the upper caloric limit for G:F would require most grains
      to be processed or fed in high-moisture form. Whether maximizing G:F results in
      the most desirable carcass composition and yield of retail cuts should be
      determined.

PMID- 16582092
TI  - Application of stable isotopes and mass isotopomer distribution analysis to the
      study of intermediary metabolism of nutrients.
AB  - Genomic investigations in animals have begun to reveal the metabolic and
      physiological functions of genes and protein products. However, a thorough
      understanding of the genomic roadmaps will require investigative approaches that
      yield qualitative and quantitative information on the activities, fluxes, and
      connectivity of pathways involved in nutrient use in farm animals; that is, the
      metabolic phenotype. Recently, the commercial availability of stable isotope
      (13C, 15N, 2H)-labeled compounds and highly accurate mass spectrometers has made
      it possible to probe the details of metabolic pathways involved in macronutrient
      use. For years, the biological sciences have exploited uniformly 13C-labeled
      substrates (e.g., glucose, amino acids, nucleic acids) and 13C-mass isotopomer
      distribution (MID) in their metabolic investigations, whereas their use in the
      animal sciences is very limited. When [U-13C] substrates are fed, infused, or
      added to cell incubations, the 13C-skeletons distribute throughout metabolic
      networks. 13C-Mass isotopomer distribution in intermediates and end products of
      the pathways provides a signature of the fluxes and activities of pathway enzymes
      traveled by the precursor molecule. This paper highlights aspects of animal
      nutrition and metabolism in which [U-13C] substrates and MID can be applied to
      investigations of amino acid, carbohydrate, and fat metabolism. We will focus on
      [U-13C] glucose as a tracer in chickens, fish, sheep, and cell cultures to
      investigate the interconnectivity of the pathways of macronutrient and nucleic
      acid metabolism, and provide demonstration of the central position of the Krebs
      cycle in preserving metabolic flexibility via anaplerotic and cataplerotic
      sequences. Exploitation of this approach in animal sciences offers endless
      opportunities to provide missing details of the biochemical networks of nutrient
      use that may prove to be strictly under genomic control.

PMID- 16582093
TI  - Measuring splanchnic amino acid metabolism in vivo using stable isotopic tracers.
AB  - The splanchnic bed comprises the liver and the portal-drained viscera (PDV). The
      PDV, which include the stomach, intestines, pancreas, and spleen, represent 4 to
      6% of BW, yet they account for 20 to 35% of whole-body protein turnover and
      energy expenditure. Because the PDV are the first to be exposed to the diet,
      their nutrient needs are met first. Consequently, the extraction of dietary
      nutrients, especially AA, by the intestine will have a critical influence on
      their availability to peripheral tissues and therefore, on whole body
      requirements. Moreover, the systemic availability of dietary AA is a key
      determinant of lean body growth rate. A complicating factor in the measurement of
      intestinal nutrient use is that the intestinal epithelial cells receive nutrients
      from 2 sources: the diet and the arterial circulation. However, combining
      measurements of the net portal balance with those of isotopic enrichments from
      enterally and intravenously administered stable isotope-labeled AA provides an in
      vivo model that can be used to determine the proportion of AA extracted by the
      intestine from either source. Using this technique in fed animals demonstrated
      that the PDV contribute significantly to the use of essential (>60% of threonine)
      and nonessential (>90% of glutamate) AA provided by the diet. The relative use by
      the PDV of individual AA from the diet and arterial inputs varies widely, and
      dietary AA are the preferred fuel over dietary glucose. Stable isotope-labeled AA
      also enable the determination of the metabolic fate of individual AA. Using this
      technique, studies have shown that an insufficient protein supply or the mode of
      feeding affects AA use by the PDV, and consequently, may affect whole-body
      growth.

PMID- 16582094
TI  - Mineral bioavailability and metabolism determined by using stable isotope
      tracers.
AB  - Definitive data on mineral bioavailability in humans and animals can be obtained
      by using isotopic tracers. The use of stable isotope tracers to study important
      issues in mineral nutrition has expanded rapidly in the past two decades,
      particularly in human nutrition studies. Stable isotopes have a number of
      advantages over radioisotopes. There is no exposure to radiation with stable
      isotopes, and some minerals have no radioisotope that can be used satisfactorily
      as a tracer. Multiple stable isotopes of one mineral and isotopes of multiple
      minerals can be administered simultaneously or sequentially. The analytical
      methods of choice for stable isotopes are thermal ionization mass spectrometry
      and inductively coupled plasma mass spectrometry (ICPMS). Thermal ionization mass
      spectrometry offers the greatest precision and accuracy, but it is slower, more
      labor intensive, and more costly than ICPMS. Bioavailability data are critical to
      establishing reliable dietary mineral requirements and recommendations. Combined
      with a computer program for compartmental modeling, mineral kinetics can be
      studied, including mineral turnover, pool sizes, and transfer rates between
      compartments. Our laboratory conducts studies using stable isotopes of Zn, Cu,
      Fe, Ca, Mg, and Mo. We have studied the effect of the amount of dietary intake of
      minerals on bioavailability and use, pregnancy and aging, and interactions among
      minerals. The research resulted in establishing new dietary recommendations for
      Cu and Mo and developing compartmental models for these minerals. Although stable
      isotopes have been used more extensively to date in humans than in animals, the
      techniques applied to humans can be used to study a number of issues important to
      optimizing feeding strategies for animal production.

PMID- 16582095
TI  - Measuring synthesis rates of nitrogen-containing polymers by using stable isotope
      tracers.
AB  - The major N-containing polymer compounds in the body include protein, RNA, and
      DNA. The endogenous gastrointestinal secretions as well as the portal-drained
      visceral and peripheral immune responses are basic physiological functions.
      Elevated endogenous secretions and immune activities, as affected by
      developmental stages, diets, and management factors, decrease the availability of
      dietary nutrients for peripheral muscle synthesis and deposition. Measurements of
      in vivo protein, RNA, and DNA synthesis rates associated with the viscera,
      peripheral immune cells, and skeletal muscles should, in principle, be the
      sensitive biochemical and cellular endpoints for studying factors affecting
      nonruminant nutrition, metabolism, and growth. The selection of stable isotope
      tracers for precursors, routes of tracer delivery, and mass spectrometric
      analyses of tracer enrichments are the major methodological considerations. To
      measure in vivo protein, RNA, and DNA synthesis rates, oral feeding with heavy
      water (2H2O), and continuous infusion of [U-13C]glucose and [15N]Gly
      intravenously for labeling the sugar moieties ribose and deoxyribose and de novo
      purine base synthesis have been established. Flooding doses of tracer Phe, for
      example, L-[ring-2H5]Phe, via the i.p. route are reliable and cost-effective for
      measuring in vivo protein synthesis rates, especially for the viscera in small
      nonruminants. Therefore, measurements of the major N-containing polymer synthesis
      rates in the viscera, the peripheral immune cells, and muscles through oral
      feeding with 2H2O and/or i.p. flooding doses of Phe tracers are the emerging
      tools for studying nonruminant nutrition, metabolism, and growth under research
      and field test conditions.

PMID- 16582096
TI  - Stable isotope methods for the in vivo measurement of lipogenesis and
      triglyceride metabolism.
AB  - Synthesis of fatty acids (via de novo lipogenesis) and triglycerides are
      important factors in fat accumulation and the efficiency of animal production.
      Recently, new stable isotope methods using heavy water (2H2O) have made possible
      the safe, and relatively easy, measurement of both of these processes in vivo in
      animals and humans over prolonged periods. These methods also provide information
      on the relative contribution of glycolysis and glyceroneogenesis to triglyceride
      synthesis under different physiological settings. The data suggest that numerous
      dietary factors, including nutrient composition and caloric content, may affect
      de novo lipogenesis. Significant differences in de novo lipogenesis have also
      been seen across species and in different tissues. The rates of triglyceride
      synthesis have been shown to be affected by diet and to differ significantly
      between different adipose depots, with metabolically active depots (e.g.,
      visceral fat) having much more rapid triglyceride turnover than subcutaneous
      depots. Dietary fat and the peroxisome proliferator-activated-gamma agonist
      rosiglitazone have both been shown to influence triglyceride synthesis rates and
      to increase glyceroneogenesis. A significant portion of triglyceride synthesis is
      not related to triglyceride accumulation but rather is secondary to active
      lipolysis and reesterification. The application of these new techniques to
      animals other than rodents will undoubtedly enhance our understanding of adipose
      tissue biology and could lead to new methods for improving animal production.

PMID- 16582097
TI  - Fast Fenton footprinting: a laboratory-based method for the time-resolved
      analysis of DNA, RNA and proteins.
AB  - 'Footprinting' describes assays in which ligand binding or structure formation
      protects polymers such as nucleic acids and proteins from either cleavage or
      modification; footprinting allows the accessibility of individual residues to be
      mapped in solution. Equilibrium and time-dependent footprinting links site
      specific structural information with thermodynamic and kinetic transitions. The
      hydroxyl radical (*OH) is a particularly valuable footprinting probe by virtue of
      it being among the most reactive of chemical oxidants; it reports the solvent
      accessibility of reactive sites on macromolecules with as fine as a single
      residue resolution. A novel method of millisecond time-resolved .OH footprinting
      has been developed based on the Fenton reaction, Fe(II) + H2O2 --> Fe(III) + *OH
      + OH-. This method can be implemented in laboratories using widely available
      three-syringe quench flow mixers and inexpensive reagents to study local changes
      in the solvent accessibility of DNA, RNA and proteins associated with their
      biological function.

PMID- 16582098
TI  - Tri-nucleotide threading for parallel amplification of minute amounts of genomic
      DNA.
AB  - Efforts to correlate genetic variations with phenotypic differences are
      intensifying due to the availability of high-density maps of single nucleotide
      polymorphisms (SNPs) and the development of high throughput scoring methods.
      These recent advances have led to an increased interest for improved multiplex
      preparations of genetic material to facilitate such whole genome analyses. Here
      we propose a strategy for the parallel amplification of polymorphic loci based on
      a reduced set of nucleotides. The technique denoted Tri-nucleotide Threading
      (TnT), allows SNPs to be amplified via controlled linear amplification followed
      by complete removal of the target material and subsequent amplification with a
      pair of universal primers. A dedicated software tool was developed for this
      purpose and variable positions in genes associated with different forms of cancer
      were analyzed using sub-nanogram amounts of starting material. The amplified
      fragments were then successfully scored using a microarray-based PrASE technique.
      The results of this study, in which 75 SNPs were analyzed, show that the TnT
      technique circumvents potential problems associated with multiplex amplification
      of SNPs from minute amounts of material. The technique is specific, sensitive and
      can be readily adapted to equipment and genotyping techniques used in other
      research laboratories without requiring changes to the preferred typing method.

PMID- 16582099
TI  - The high-mobility-group domain of Sox proteins interacts with DNA-binding domains
      of many transcription factors.
AB  - Sox proteins are widely believed to team up with other transcription factors as
      partner proteins to perform their many essential functions during development. In
      this study, yeast two-hybrid screens identified transcription factors as a major
      group of interacting proteins for Sox8 and Sox10. Interacting transcription
      factors were very similar for these two group E Sox proteins and included
      proteins with different types of DNA-binding domains, such as homeodomain
      proteins, zinc finger proteins, basic helix-loop-helix and leucine zipper
      proteins. In all cases analyzed, the interaction involved the DNA-binding domain
      of the transcription factor which directly contacted the C-terminal part of the
      high-mobility-group (HMG) domain. In particular, the C-terminal tail region
      behind helix 3 of the HMG domain was shown by mutagenesis to be essential for
      interaction and transcription factor recruitment. The HMG domain thus not only
      possesses DNA-binding and DNA-bending but also protein-interacting ability which
      may be equally important for the architectural function of Sox proteins on their
      target gene promoters.

PMID- 16582100
TI  - BMI1 is a target gene of E2F-1 and is strongly expressed in primary
      neuroblastomas.
AB  - The oncogene BMI1 encodes a polycomb group transcription factor that is required
      for embryonic development and self-renewal of stem cells. Despite these important
      functions little is known about the regulation of BMI1 expression. A cDNA
      microarray based search for target genes of E2F-1 in neuroblastoma cells
      expressing a 4-OHT-regulated E2F-1-ER fusion protein identified many hitherto
      unknown E2F-1 regulated genes. A total of 10% of these genes, including BMI1,
      encode proteins that function primarily in the regulation of gene expression. The
      BMI1 promoter contains a putative E2F binding site that was required for the
      activation of a BMI1 promoter-dependent reporter construct by E2F-1. Chromatin
      immunoprecipitation revealed 4-OHT-dependent binding of E2F-1-ER and binding of
      endogenous E2F-1 to the BMI1 promoter in tumor cells. We have previously shown
      activation of the oncogene MYCN by E2F. Thus, in neuroblastomas deregulated E2F-1
      can activate two oncogenes, MYCN and BMI1 that are known to co-operate in tumor
      formation. Consistent with a role of Bmi1 in neuroblastoma tumorigenesis we found
      strong Bmi1 expression in primary neuroblastomas. Our results reveal a novel link
      between E2F and polycomb transcription factors and suggest a role of Bmi1 in
      neuroblastomas.

PMID- 16582101
TI  - Distance determination by GIY-YIG intron endonucleases: discrimination between
      repression and cleavage functions.
AB  - GIY-YIG homing endonucleases are modular proteins, with conserved N-terminal
      catalytic domains connected by linkers to C-terminal DNA-binding domains. I-TevI,
      the T4 phage GIY-YIG intron endonuclease, functions both in promoting td intron
      homing, and in acting as a transcriptional autorepressor. Repression is achieved
      by binding to an operator, which is cleaved at 100-fold reduced efficiency
      relative to the intronless homing site. The linker includes a zinc finger, which
      functions in distance determination, to constrain the catalytic domain to cleave
      the homing site at a fixed position. Here we show that I-BmoI, a related GIY-YIG
      endonuclease lacking a zinc finger, also possesses some cleavage distance
      discrimination. Furthermore, hybrid endonucleases constructed by swapping the
      domains of I-BmoI and I-TevI are active, precise and demonstrate that features
      other than the zinc finger facilitate distance determination. Most importantly, I
      TevI zinc finger mutants cleave the operator more efficiently than the homing
      site, the converse of wild-type protein. These results are consistent with the
      zinc finger acting as a measuring device, directing efficient cleavage of the
      homing site to promote intron mobility, while reducing cleavage at the operator
      to ensure transcriptional autorepression and phage viability.

PMID- 16582102
TI  - The expression profile of microRNAs in mouse embryos.
AB  - MicroRNAs (miRNAs), which are non-coding RNAs 18-25 nt in length, regulate a
      variety of biological processes, including vertebrate development. To identify
      new species of miRNA and to simultaneously obtain a comprehensive quantitative
      profile of small RNA expression in mouse embryos, we used the massively parallel
      signature sequencing technology that potentially identifies virtually all of the
      small RNAs in a sample. This approach allowed us to detect a total of 390 miRNAs,
      including 195 known miRNAs covering approximately 80% of previously registered
      mouse miRNAs as well as 195 new miRNAs, which are so far unknown in mouse. Some
      of these miRNAs showed temporal expression profiles during prenatal development
      (E9.5, E10.5 and E11.5). Several miRNAs were positioned in polycistron clusters,
      including one particular large transcription unit consisting of 16 known and 23
      new miRNAs. Our results indicate existence of a significant number of new miRNAs
      expressed at specific stages of mammalian embryonic development and which were
      not detected by earlier methods.

PMID- 16582103
TI  - The DNA-protein interaction modes of FEN-1 with gap substrates and their
      implication in preventing duplication mutations.
AB  - Flap endonuclease-1 (FEN-1) is a structure-specific nuclease best known for its
      involvement in RNA primer removal and long-patch base excision repair. This
      enzyme is known to possess 5'-flap endo- (FEN) and 5'-3' exo- (EXO) nuclease
      activities. Recently, FEN-1 has been reported to also possess a gap endonuclease
      (GEN) activity, which is possibly involved in apoptotic DNA fragmentation and the
      resolution of stalled DNA replication forks. In the current study, we compare the
      kinetics of these activities to shed light on the aspects of DNA structure and
      FEN-1 DNA-binding elements that affect substrate cleavage. By using DNA binding
      deficient mutants of FEN-1, we determine that the GEN activity is analogous to
      FEN activity in that the single-stranded DNA region of DNA substrates interacts
      with the clamp region of FEN-1. In addition, we show that the C-terminal
      extension of human FEN-1 likely interacts with the downstream duplex portion of
      all substrates. Taken together, a substrate-binding model that explains how FEN
      1, which has a single active center, can have seemingly different activities is
      proposed. Furthermore, based on the evidence that GEN activity in complex with
      WRN protein cleaves hairpin and internal loop substrates, we suggest that the GEN
      activity may prevent repeat expansions and duplication mutations.

PMID- 16582104
TI  - Experimental and computational investigations of Ser10 and Lys13 in the binding
      and cleavage of DNA substrates by Escherichia coli DNA topoisomerase I.
AB  - Ser10 and Lys13 found near the active site tyrosine of Escherichia coli DNA
      topoisomerase I are conserved among the type IA topoisomerases. Site-directed
      mutagenesis of these two residues to Ala reduced the relaxation and DNA cleavage
      activity, with a more severe effect from the Lys13 mutation. Changing Ser10 to
      Thr or Lys13 to Arg also resulted in loss of DNA cleavage and relaxation activity
      of the enzyme. In simulations of the open form of the topoisomerase-DNA complex,
      Lys13 interacts directly with Glu9 (proposed to be important in the catalytic
      mechanism). This interaction is removed in the K13A mutant, suggesting the
      importance of lysine as either a proton donor or a stabilizing cation during
      strand cleavage, while the Lys to Arg mutation significantly distorts catalytic
      residues. Ser10 forms a direct hydrogen bond with a phosphate group near the
      active site and is involved in direct binding of the DNA substrate; this
      interaction is disturbed in the S10A and S10T mutants. This combination of a
      lysine and a serine residue conserved in the active site of type IA
      topoisomerases may be required for correct positioning of the scissile phosphate
      and coordination of catalytic residues relative to each other so that DNA
      cleavage and subsequent strand passage can take place.

PMID- 16582106
TI  - Btk expression is controlled by Oct and BOB.1/OBF.1.
AB  - BOB.1/OBF.1 is a lymphocyte-restricted transcriptional coactivator. It binds
      together with the Oct1 and Oct2 transcription factors to DNA and enhances their
      transactivation potential. Mice deficient for the transcriptional coactivator
      BOB.1/OBF.1 show several defects in differentiation, function and signaling of B
      cells. In search of BOB.1/OBF.1 regulated genes we identified Btk--a cytoplasmic
      tyrosine kinase-as a direct target of BOB.1/OBF.1. Analyses of the human as well
      as murine Btk promoters revealed a non-consensus octamer site close to the start
      site of transcription. Here we show that Oct proteins together with BOB.1/OBF.1
      are able to form ternary complexes on these sites in vitro and in vivo. This in
      turn leads to the induction of Btk promoter activity in synergism with the
      transcription factor PU.1. Btk, like BOB.1/OBF.1, plays a critical role in B cell
      development and B cell receptor signalling. Therefore the down-regulation of Btk
      expression in BOB.1/OBF.1-deficient B cells could be related to the functional
      and developmental defects observed in BOB.1/OBF.1-deficient mice.

PMID- 16582107
TI  - When does a "less than perfect" sex life become female sexual dysfunction?

PMID- 16582105
TI  - Acetylation of UBF changes during the cell cycle and regulates the interaction of
      UBF with RNA polymerase I.
AB  - The upstream binding factor UBF, an activator of RNA polymerase I transcription,
      is posttranslationally modified by phosphorylation and acetylation. We found that
      in NIH3T3 cells, UBF is acetylated in S-phase but not in G1-phase. To assess the
      role of acetylation in regulation of UBF activity, we have established an NIH3T3
      cell line that inducibly overexpresses HDAC1. Both in vivo and in vitro, HDAC1
      efficiently hypoacetylates UBF. Immunoprecipitation with antibodies against the
      Pol I-associated factor PAF53 co-precipitated UBF in mock cells but not in cells
      overexpressing HDAC1. Pull-down experiments showed that acetylation of UBF
      augments the interaction with Pol I. Consistent with acetylation of UBF being
      important for association of PAF53 and recruitment of Pol I, the level of Pol I
      associated with rDNA and pre-rRNA synthesis were reduced in cells overexpressing
      HDAC1. The results suggest that acetylation and deacetylation of UBF regulate
      rRNA synthesis during cell cycle progression.

PMID- 16582108
TI  - Can a 29% cesarean delivery rate possibly be justified?

PMID- 16582109
TI  - Sexual activity and function in middle-aged and older women.
AB  - OBJECTIVE: Data on the sexual activity of middle-aged and older women are scant
      and vary widely. This analysis estimates the prevalence and predictors of sexual
      activity and function in a diverse group of women aged 40-69 years. METHODS: The
      Reproductive Risk Factors for Incontinence Study at Kaiser (RRISK) was a
      population-based study of 2,109 women aged 40-69 years who were randomly selected
      from long-term Kaiser Permanente members. Women completed self-report
      questionnaires on sexual activity, comorbidities, and general quality of life.
      Logistic and linear regression and proportional odds models were used when
      appropriate to identify correlates of sexual activity, frequency, satisfaction,
      and dysfunction. RESULTS: Mean age was 55.9 (+/- 8) years and nearly three
      fourths of the women were sexually active. Of the sexually active women, 60% had
      sexual activity at least monthly, approximately two thirds were at least somewhat
      satisfied, and 33% reported a problem in one or more domains. Monthly or more
      frequent sexual activity was associated with younger age, higher income, being in
      a significant relationship, a history of moderate alcohol use, and lower body
      mass index (BMI) (all P < .05). Satisfaction with sexual activity was associated
      with African-American race, lower BMI, and higher mental health score (all P <
      .05). More sexual dysfunction was associated with having a college degree or
      greater, poor health, being in a significant relationship, and a low mental
      health score (all P < .05). CONCLUSION: Middle-aged and older women engage in
      satisfying sexual activity, and one third reported problems with sexual function.
      Demographic factors as well as some issues associated with aging can adversely
      affect sexual frequency, satisfaction, and function. LEVEL OF EVIDENCE: II-3.

PMID- 16582110
TI  - Effect of parity on sexual function: an identical twin study.
AB  - OBJECTIVE: To assess the impact of childbirth on female sexual function by using
      an identical twin study design. METHODS: A survey including the Pelvic Organ
      Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) was administered to
      542 twin sisters, and PISQ-12 scores of 29 twin pairs discordant for parity were
      compared. Multiple linear regression models were used to evaluate impact on total
      PISQ-12 scores in 276 identical, sexually active twins. Three models were used 1)
      to evaluate the effect of parity and general risk factors, 2) to examine the
      impact of birth mode, and 3) to examine the role of episiotomy and operative
      delivery. RESULTS: Mean PISQ-12 scores were significantly higher for discordant
      nulliparous twins than for parous twins (102.5 versus 93.5, P < .001). The mean
      (standard deviation) PISQ-12 score was 99.3 (11.7). Age of 50 years or older
      (difference in mean scores -5.4, P = .019), stress urinary incontinence (-3.3, P
      = .02), urge urinary incontinence (-5.9, P < .001), parity (-6.5, P < .001), and
      fecal incontinence (-5.7, P = .048) were associated with decreased mean PISQ
      scores in the univariable analysis. Parity (-4.9, P < .001) and urge urinary
      incontinence (-4.3, P = .009) were the only factors remaining independently
      predictive of diminished sexual function in the multivariable analysis. Mode of
      delivery did not significantly affect mean PISQ scores (P = .763). Among women
      who had vaginal deliveries only, neither episiotomy nor operative delivery was
      associated with change in PISQ scores (P = .553). CONCLUSION: Nulliparous women
      reported superior sexual satisfaction scores compared with parous women,
      regardless of age and mode of delivery. Childbirth appears to have a lasting
      impact on sexual function, due to psychological more than physical factors, well
      beyond the postpartum period. LEVEL OF EVIDENCE: II-2.

PMID- 16582111
TI  - Previous cesarean delivery and risks of placenta previa and placental abruption.
AB  - OBJECTIVE: To examine the association between cesarean delivery and previa and
      abruption in subsequent pregnancies. METHODS: A retrospective cohort study of
      first 2 (n = 156,475) and first 3 (n = 31,102) consecutive singleton pregnancies
      using the 1989-1997 Missouri longitudinally linked data were performed. Relative
      risk (RR) was used to quantify the associations between cesarean delivery and
      risks of previa and abruption in subsequent pregnancies, after adjusting for
      several confounders. RESULTS: Rates of previa and abruption were 4.4 (n = 694)
      and 7.9 (n = 1,243) per 1,000 births, respectively. The pregnancy after a
      cesarean delivery was associated with increased risk of previa (0.63%) compared
      with a vaginal delivery (0.38%, RR 1.5, 95% confidence interval [CI] 1.3-1.8).
      Cesarean delivery in the first and second births conferred a two-fold increased
      risk of previa in the third pregnancy (RR 2.0, 95% CI 1.3-3.0) compared with
      first two vaginal deliveries. Women with a cesarean first birth were more likely
      to have an abruption in the second pregnancy (0.95%) compared with women who had
      a vaginal first birth (0.74%, RR 1.3, 95% CI 1.2-1.5). Two consecutive cesarean
      deliveries were associated with a 30% increased risk of abruption in the third
      pregnancy (RR 1.3, 95% CI 1.0-1.8). A second pregnancy within a year after a
      cesarean delivery was associated with increased risks of previa (RR 1.7, 95% CI
      0.9-3.1) and abruption (RR 1.5, 95% CI 1.1-2.3). CONCLUSION: A cesarean first
      birth is associated with increased risks of previa and abruption in the second
      pregnancy. There is a dose-response pattern in the risk of previa, with
      increasing number of prior cesarean deliveries. A short interpregnancy interval
      is associated with increased risks of previa and abruption. LEVEL OF EVIDENCE: II
      2.

PMID- 16582112
TI  - Outcome after transabdominal cervicoisthmic cerclage.
AB  - OBJECTIVE: To estimate benefits and risks of transabdominal cervicoisthmic
      cerclage in women with cervical insufficiency in whom transvaginal cerclage is
      considered surgically unfeasible. METHODS: This was an observational cohort study
      with historical controls of 101 pregnancies after transabdominal cervicoisthmic
      cerclage in 101 women with a classic history of cervical insufficiency and severe
      cervical defects precluding transvaginal cerclage. RESULTS: Median gestational
      age at elective transabdominal cerclage (n = 95) was 14 (range 12-16) weeks and
      at emergency cerclage (n = 6) was 18 (range 17-22) weeks. Perioperative
      complications were blood loss 500 mL or more (n = 3) and rupture of membranes (n
      = 2). Patients were delivered by cesarean. Before cerclage 76% (95% confidence
      interval [CI] 70.2-81.1%) of births occurred before 32 weeks of gestation; total
      neonatal survival was 27.5% (95% CI 22.5-33.8%). After transabdominal
      cervicoisthmic cerclage 7% (95% CI 2.9-13.9%) of births took place before 32
      weeks of gestation, and total neonatal survival was 93.5% (95% CI 85.5-96.6%).
      CONCLUSION: In women with a classic history of cervical insufficiency and a
      traumatized cervix that precludes transvaginal cerclage, transabdominal
      cervicoisthmic cerclage is associated with successful outcome in the absence of
      procedure-related major complications. LEVEL OF EVIDENCE: II-2.

PMID- 16582113
TI  - Placental abruption in term and preterm gestations: evidence for heterogeneity in
      clinical pathways.
AB  - OBJECTIVE: To estimate the magnitude of associations of acute and chronic
      processes with abruption in preterm and term gestations. METHODS: A retrospective
      cohort study was performed using data on women that delivered singleton live
      births and stillbirths at 20 or more weeks of gestation in the United States,
      1995-2002 (n = 30,378,902). Rates of 1) acute-inflammation-associated clinical
      conditions (premature rupture of membranes and intrauterine infection); 2)
      chronic processes associated with vascular dysfunction or chronic inflammation
      (chronic and pregnancy-induced hypertension, preexisting or gestational diabetes,
      small for gestational age, and maternal smoking); and 3) both acute and chronic
      processes, were examined among women with and without abruption. Rates were
      examined separately among preterm (< 37 weeks) and term births, with adjustment
      for confounders. Relative risk (RR) for aforementioned groups in relation to
      abruption was derived from multivariate logistic regression models after
      adjusting for potential confounders. RESULTS: At preterm gestation, the rates of
      acute-inflammation-associated conditions were higher among women with than
      without abruption (12.0% compared with 10.2%; RR 1.38, 95% confidence interval
      [CI] 1.34-1.42). At term, acute-inflammation-associated conditions were present
      in 4.2% and 3.3% of births with and without abruption, respectively (RR 1.39, 95%
      CI 1.33-1.45). At preterm gestation, the rates of chronic processes were 43.9%
      and 30.0% among women with and without abruption, respectively (RR 1.87, 95% CI
      1.85-1.90). At term, the corresponding rates of chronic processes were 41.0% and
      22.7%, respectively (RR 2.37, 95% CI 2.34-2.41). Association between both acute
      and chronic processes and abruption are similar to those of acute-inflammation
      associated conditions. CONCLUSION: Among women with placental abruption,
      conditions associated with acute inflammation are more prevalent at preterm than
      term gestations, whereas chronic processes are present throughout gestation.
      LEVEL OF EVIDENCE: II-2.

PMID- 16582114
TI  - Effect of coitus on recurrent preterm birth.
AB  - OBJECTIVE: To estimate the impact of sexual behavior on the risk of recurrent
      spontaneous preterm birth at less than 37 weeks of gestation. METHODS: This is a
      secondary analysis of a multicenter, blinded observational study of endovaginal
      sonographic examinations performed at 16-18 weeks of gestation on 187 women with
      singleton gestations who were at high risk for recurrent spontaneous preterm
      birth (prior spontaneous preterm birth at < 32 weeks of gestation). At the time
      of enrollment, each woman was interviewed by a research nurse with regard to her
      sexual history. The patient was asked about the number of sexual partners in her
      lifetime, the number of sexual partners since the start of her pregnancy, and, on
      average, the frequency of intercourse per week in the preceding month. RESULTS: A
      total of 165 pregnancies were available for this analysis. The population
      incidence of spontaneous preterm birth at less than 37 weeks of gestation in the
      study pregnancy was 36%. An increasing number of sexual partners in a woman's
      lifetime was associated with an increased risk of spontaneous preterm delivery
      (one partner 19%, 2-3 partners 29%, >or= 4 partners 44%, P = .007), whereas the
      number of sexual partners since the start of pregnancy was not (P = .42). Women
      who reported infrequent sexual intercourse during early pregnancy had an
      incidence of recurrent spontaneous preterm birth of 28% compared with 38% in
      those women who reported some intercourse (P = .35). CONCLUSION: Self-reported
      coitus during early pregnancy was not associated with an increased risk of
      recurrent preterm delivery. There was an association between increasing number of
      sexual partners in a woman's lifetime and recurrent preterm delivery. LEVEL OF
      EVIDENCE: II-2.

PMID- 16582115
TI  - Depressive symptoms and health-related quality of life in early pregnancy.
AB  - OBJECTIVE: Depressive symptoms can be associated with lower health-related
      quality of life in late pregnancy. Few studies have quantified the effect of
      depressive symptoms in early pregnancy or among a racially and economically
      diverse group. Our goal was to estimate the independent association of depressive
      symptoms with health-related quality of life among a diverse group of women in
      early pregnancy. METHODS: We conducted a cross-sectional study of 175 pregnant
      women receiving prenatal care in a community and university-based setting. We
      related the presence of depressive symptoms, defined as a Center for
      Epidemiologic Studies Depression Scale score of 16 or more to health-related
      quality of life scores from the 8 Medical Outcomes Study Short Form domains:
      Physical Functioning, Role-Physical, Bodily Pain, Vitality, General Health,
      Social Functioning, Role-Emotional, and Mental Health. Quantile regression was
      used to measure the independent association of depressive symptoms with each of
      the 8 domains. RESULTS: The study sample was 49% African American, 38% white, and
      11% Asian. Mean (+/- standard deviation) gestational age was 14 +/- 6 weeks. The
      prevalence of depressive symptoms was 15%. Women with depressive symptoms had
      significantly lower health-related quality of life scores in all domains except
      Physical Functioning. After adjustment for sociodemographic, clinical, and social
      support factors, depressive symptoms were associated with health-related quality
      of life scores that were 30 points lower in Role-Physical, 19 points lower in
      Bodily Pain, 10 points lower in General Health, and 56 points lower in Role
      Emotional. CONCLUSION: Women in early pregnancy with depressive symptoms have
      poor health-related quality of life. Early identification and management of
      depressive symptoms in pregnant women may improve their sense of well-being.
      LEVEL OF EVIDENCE: II-2.

PMID- 16582117
TI  - Cost-effectiveness of screening strategies for Gonorrhea among females in private
      sector care.
AB  - OBJECTIVE: To identify the optimal screening algorithm for gonorrhea infection
      among females in private sector care, using cost-effectiveness analysis. METHODS:
      We compared 6 strategies using decision analysis for urine nucleic acid
      amplification testing for gonorrhea testing in a theoretical cohort of 10,000
      females aged 15-35 years: 1) screen women aged younger than 25 years; 2) screen
      women aged younger than 30 years; 3) screen women aged younger than 25 years who
      report any risk (pregnant, drug use, new sexual partner < 30 days); 4) screen
      women aged younger than 30 years who report any risk; 5) screen women aged
      younger than 25 years or those who report any risk; and 6) screen women aged
      younger than 30 years or those who report any risk. Infection prevalence and
      sensitivity and specificity were by direct observation from a retrospective
      cohort of females attending the Baltimore City Sexually Transmitted Disease
      Clinics between 1999 and 2002. The main outcome measures were untreated gonorrhea
      cases and their sequelae in women, transmission to a male partner, congenital
      outcomes, and cost to prevent a case. RESULTS: Prevalence of gonorrhea was 3.0%.
      Not screening would result in 300 untreated cases. Not screening was cost-saving
      over all screening strategies. Strategy 6 resulted in the fewest cases of
      untreated infection (82), although Strategy 3 was the most cost-effective of the
      screening strategies. Univariate sensitivity analysis identified a threshold of
      4.75% gonorrhea prevalence, more than which Strategy 3 became cost-saving over
      not screening. CONCLUSION: Screening is recommended for females aged younger than
      25 years with specific risks in populations with a gonorrhea prevalence of 4.75%
      or greater. LEVEL OF EVIDENCE: II-2.

PMID- 16582116
TI  - Effect of human immunodeficiency virus-1 infection on treatment outcome of acute
      salpingitis.
AB  - OBJECTIVE: To examine the effect of human immunodeficiency virus (HIV)-1
      infection on treatment outcome of laparoscopically verified acute salpingitis.
      METHODS: Women aged 18-40 years with laparoscopically verified acute salpingitis
      received antibiotic therapy that included cefotetan 2 g intravenously and
      doxycycline 100 mg orally every 12 hours and laparoscopically guided drainage of
      tuboovarian abscesses of 4 cm or more. Clinical investigators blinded to HIV-1
      serostatus used predetermined clinical criteria, including calculation of a
      clinical severity score and a standard treatment protocol to assess response to
      therapy. RESULTS: Of the 140 women with laparoscopically confirmed acute
      salpingitis, 61 (44%) women had mild, 38 (27%) had moderate, and 41 (29%) had
      severe disease (ie, pyosalpinx, tuboovarian abscesses, or both). Fifty-three
      (38%) were HIV-1-infected. Severe disease was more common in HIV-1-infected in
      comparison with HIV-1-uninfected women (20 [38%] compared with 21 [24%], P =
      .02). Defined as time of hospital discharge or 75% or more reduction in baseline
      clinical severity score, HIV-1-infected women with severe (6 days [4-16] compared
      with 5 days [3-9], P = .09) but not those with either mild (4 days [2-6] compared
      with 4 days [2-6] P = .4) or moderate salpingitis (4 days [3-7] compared with 4
      days [3-6] P = .32) tended to take longer to meet criteria for clinical
      improvement. The need for intravenous clindamycin or additional surgery was not
      different in HIV-1-infected and uninfected cases (15 [28%] compared with 18
      [21%], P = .3). CONCLUSION: Although HIV-1 infection may prolong hospitalization
      in women with severe salpingitis, all women hospitalized with acute salpingitis
      responded promptly to antibiotic therapy and surgical drainage regardless of HIV
      1 infection status. LEVEL OF EVIDENCE: II-2.

PMID- 16582118
TI  - Human papillomavirus triage for young women with atypical squamous cells of
      undetermined significance.
AB  - OBJECTIVE: Human papillomavirus testing is a cost-effective strategy for the
      management of atypical squamous cells of undetermined significance. Young women
      have a high prevalence of transient human papillomavirus infections and low
      incidence high-grade cervical lesions, which may limit the usefulness of human
      papillomavirus testing in this cohort. We sought to estimate the usefulness of
      human papillomavirus testing for young women with atypical squamous cells of
      undetermined significance. METHODS: A retrospective study of women with atypical
      squamous cells of undetermined significance was undertaken. Reflex human
      papillomavirus results and pathologic follow-up were evaluated. Age-stratified
      rates of human papillomavirus positivity, rates of high-grade dysplasia, and
      sensitivity and specificity were estimated. RESULTS: A total of 1,290 women with
      atypical squamous cells of undetermined significance cytology were identified.
      The rate of human papillomavirus positivity decreased with age from 55% for those
      aged 25 years or younger to 12% for women aged older than 50 years (P < .001).
      The cumulative rate of high-grade lesions increased with age; 12% for patients
      aged 25 years or younger compared with 24% for women aged older than 50 years (P
      = .05). A negative human papillomavirus test more effectively excluded high-grade
      disease in the young women. No high-grade lesions were detected in the human
      papillomavirus negative women aged 25 years or younger compared with 3.8% of
      those aged older than 50 years (P = .04). The sensitivity for detection of high
      grade disease was higher in women aged younger than 25 years compared with those
      aged older than 50 years (100% compared with 50%), whereas specificity was lower
      (14% compared with 44%). CONCLUSION: Given the high prevalence of human
      papillomavirus and low occurrence of high-grade lesions in young women with
      atypical squamous cells of undetermined significance, a human papillomavirus
      based triage strategy will result in the referral of a large number of women for
      colposcopy and may limit its cost-effectiveness. LEVEL OF EVIDENCE: III.

PMID- 16582119
TI  - Prediction of persistence or recurrence after conization for cervical
      intraepithelial neoplasia III.
AB  - OBJECTIVE: To estimate the predictive factors for persistent/recurrent disease
      before and after conization for cervical intraepithelial neoplasia III. METHODS:
      Patients who received conization due to histologic diagnosis of cervical
      intraepithelial neoplasia III from 1998 to 2000 and who had at least one
      cytologic/histologic follow-up within one year of conization (n = 449) were
      enrolled in our study. All available demographic and pathologic parameters were
      analyzed. RESULTS: We performed multivariable logistic regression analysis to
      identify predictive factors for cervical intraepithelial neoplasia III
      persistence/recurrence. Age (greater than 50 years) was the only preoperative
      predictor and had an odds ratio equaling 3.070 (95% confidence interval [CI]
      1.421-6.630, P = .004). Post-cone endocervical curettage was found to be the most
      statistically significant factor for predicting persistent disease (odds ratio
      7.940, 95% CI 3.428-18.390, P < .001). Positive endocervical curettage was
      associated with 65.5% (36/55) of persistent disease, whereas negative
      endocervical curettage was associated with only 7.6% (26/342). Positive
      endocervical resection margins and multiple-quadrant disease also had predictive
      values with odds ratios equaling 2.972 (95% CI 1.401-6.281, P = .004) and 2.180
      (95% CI 1.014-4.689, P = .046), respectively. The positive predictive values for
      age (> 50 years), positive endocervical curettage, positive endocervical
      resection margin, and multiple quadrant disease were 31.7%, 65.5%, 40.0%, and
      21.9%, respectively. CONCLUSION: We found that age is the only preoperative
      predictive factor. Pathologic parameters, including endocervical curettage,
      endocervical resection margins, and multiple-quadrant disease are the only
      postoperative predictive factors for cervical intraepithelial neoplasia
      persistence or recurrence found in our study. These factors should be considered
      in patient management before and after therapeutic conization for cervical
      intraepithelial neoplasia III. LEVEL OF EVIDENCE: II-3.

PMID- 16582120
TI  - The association between persistent occiput posterior position and neonatal
      outcomes.
AB  - OBJECTIVE: To examine the effect of persistent occiput posterior position on
      neonatal outcome. METHODS: This is a retrospective cohort study of 31,392 term,
      cephalic, singleton births. Women with neonates born in persistent occiput
      posterior position at delivery were compared to those with occiput anterior
      position. Women with occiput transverse position were excluded. The association
      between occiput posterior position and neonatal outcomes, including 5-minute
      Apgar scores, umbilical cord gases, meconium-stained amniotic fluid, meconium
      aspiration syndrome, birth trauma, admission to the intensive care nursery, and
      length of stay were examined using chi(2) and Student t tests. Potential
      confounders (maternal age, ethnicity, parity, gestational age, epidural
      anesthesia, labor induction, length of labor, meconium, chorioamnionitis, birth
      weight, and year of delivery) were controlled for by using multivariable logistic
      regression and linear regression analyses. RESULTS: There were 2,591 (8.2%)
      neonates delivered in occiput posterior position of the total cohort of 31,392
      deliveries. Compared with occiput anterior, neonates delivered in occiput
      posterior position had higher risks for adverse outcomes, including 5-minute
      Apgar score less than 7 (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17
      1.91), acidemic umbilical cord gases (OR 2.05, 95% CI 1.52-2.77), meconium
      stained amniotic fluid (OR 1.29, 95% CI 1.17-1.42), birth trauma (OR 1.77, 95% CI
      1.22-2.57), admission to the intensive care nursery (OR 1.57, 95% CI 1.28-1.92),
      and longer neonatal stay in the hospital (OR 2.69, 95% CI 2.22-3.25). CONCLUSION:
      Persistent occiput posterior position at delivery is associated with higher risks
      of adverse neonatal outcomes compared with neonates delivered in the occiput
      anterior position. This information may be important in counseling women who
      experience persistent occiput posterior position in labor. LEVEL OF EVIDENCE: II
      2.

PMID- 16582121
TI  - Threatened miscarriage as a predictor of obstetric outcome.
AB  - OBJECTIVE: To investigate prospectively the risk of adverse pregnancy outcome in
      women presenting with first-trimester threatened miscarriage. METHODS: A
      prospective cohort study was performed on 214 women presenting with bleeding in
      the first trimester and 214 asymptomatic age-matched controls. Main outcome
      measures included gestational age and weight at delivery and incidence of adverse
      pregnancy outcome. RESULTS: The first-trimester miscarriage rate, after
      confirmation of viability in the threatened miscarriage group, was 9.3%. Compared
      with controls, women presenting with threatened miscarriage were more likely to
      deliver prematurely, 5.6% compared with 11.9%, respectively, (relative risk 2.29,
      95% confidence interval 1.4-4.6), and this was most likely to be between 34 and
      37 weeks. They were also more likely to have preterm prelabor rupture of
      membranes, 1.9% compared with 7%, respectively, (relative risk 3.72, 95%
      confidence interval 1.2-11.2). Overall, there was no difference in mean birth
      weight and in the incidence of other obstetric complications between the 2
      groups; however, women in the threatened miscarriage group were more likely to
      deliver neonates between 1,501 g and 2,000 g (P = .04). CONCLUSION: Women with
      threatened miscarriage in the first trimester are at increased risk of premature
      delivery, and this risk factor should be taken into consideration when deciding
      upon antenatal surveillance and management of their pregnancies. LEVEL OF
      EVIDENCE: II-0.

PMID- 16582122
TI  - Is small for gestational age a marker of future fetal survival in utero?
AB  - OBJECTIVE: We sought to assess whether small for gestational age is a risk factor
      for stillbirth of a subsequent sibling. METHODS: The Missouri maternally linked
      cohort data set, containing data on births from 1978 through 1997, was used. We
      identified the study group (women who delivered a SGA infant in the first
      pregnancy) and a comparison group (women who delivered a non-SGA infant in their
      first pregnancy) and compared the outcome (stillbirth) in the second pregnancy
      between both groups. RESULTS: We analyzed information on the first and second
      pregnancies of 402,015 women (43,549 [10.8%] in the study arm and 358,466 [89.2%]
      in the comparison arm). Of the 1,883 cases of stillbirth in the second pregnancy,
      314 cases occurred in mothers with a history of SGA (stillbirth rate 7.2/1,000)
      and 1,569 in the comparison group (stillbirth rate 4.4/1,000), P < .001. The
      adjusted risk of stillbirth was 60% higher in women with a prior SGA (odds ratio
      [OR] 1.6, 95% confidence interval [CI] 1.4-1.8). The risk for stillbirth in the
      second pregnancy increased with decreasing gestational age at birth of the SGA
      infant in the first pregnancy (term: OR 1.4, 95% CI 1.2-1.6; preterm: OR 2.8, 95%
      CI 2.0-3.8; and very preterm: OR 4.2, 95% CI 2.4-7.3), P for trend < .001.
      CONCLUSION: Small for gestational age is a marker for subsequent stillbirth, and
      the risk rises with decreasing gestational age of the SGA birth. This information
      is potentially useful for counseling parents of SGA infants. LEVEL OF EVIDENCE:
      II-2.

PMID- 16582123
TI  - Outcome of second delivery after prior macrosomic infant in women with normal
      glucose tolerance.
AB  - OBJECTIVE: Our aim was to estimate the obstetric outcome of second delivery in
      women with normal glucose tolerance whose first fetus was macrosomic (fetal
      weight >/= 4,500 g). METHODS: Primiparas delivering a macrosomic infant during
      the years 1997-2000 were identified from a hospital computer database, and the
      obstetric outcome of a second delivery was analyzed up until June 2003. A control
      group (birth weight 3,000-3,500 g) served for comparison. RESULTS: Among 13,020
      first pregnancies, 301 (2.3%) were macrosomic. A similar proportion in the
      macrosomic group, 156 of 301 (52%), and control group, 171 of 300 (57%), returned
      for second delivery (P = .252). Compared with controls, first macrosomic
      deliveries were characterized by higher rates of operative delivery, anal
      sphincter injury, and shoulder dystocia. At second delivery, 32% of neonates in
      the macrosomic group and 0.3% in the control group weighed 4,500 g or more (P <
      .001). More prelabor cesareans were performed in the macrosomic group compared
      with controls (27 of 156, 17.3%, compared with 8 of 171, 4.7%; P < .001). Among
      104 women in the macrosomic group who labored after first vaginal delivery, 99%
      (103 of 104) delivered vaginally again compared with 44% (11 of 25) who labored
      after primiparous cesarean delivery (P < .001), which compares with 97% (146 of
      150) and 77% (10 of 13), respectively, in the control group. CONCLUSION: Despite
      a one-third recurrence of macrosomia, first vaginal delivery of a macrosomic
      infant was associated with a high incidence of second vaginal delivery.
      Conversely, primiparous macrosomic cesarean delivery conveyed a high risk (56%)
      for repeat intrapartum cesarean whether macrosomia recurred or not. LEVEL OF
      EVIDENCE: II-2.

PMID- 16582124
TI  - Oral clindamycin and histologic chorioamnionitis in women with abnormal vaginal
      flora.
AB  - OBJECTIVE: Oral clindamycin reduced late miscarriage and preterm birth in
      asymptomatic women with bacterial vaginosis or intermediate flora. We
      investigated whether clindamycin reduced the incidence of histologic
      chorioamnionitis as a mechanism for these beneficial effects. METHODS: This was a
      subanalysis of 126 participants from a larger randomized controlled trial. We
      compared the incidence of histologic chorioamnionitis between the clindamycin and
      placebo groups. Histologic chorioamnionitis was diagnosed by the presence of
      polymorphonuclear leukocytes, separately in the amnion and chorion, decidua,
      fetal surface of the placenta, the walls of fetal chorionic vessels, umbilical
      cord, or in the subchorionic fibrin layer. Microbiologic cultures were done on
      swabs from the space between the chorion and amnion layers. RESULTS:
      Histopathologic results were available for 122 placentas, 62 (51%) and 60 (49%)
      in the clindamycin and placebo groups, respectively. There were no significant
      differences in inflammation between the groups in the decidua (41% compared with
      43%), membranes (25% compared with 41%), fetal vessels (16% compared with 14%),
      or subchorionic fibrin (32% compared with 34%). Adjusting for gestational age,
      ethnic origin, or history of miscarriage did not alter the results. There were no
      significant differences in the outcomes of pregnancy between women with and
      without inflammation, either before or after adjustment for treatment group.
      CONCLUSION: Although oral clindamycin reduced late miscarriage and preterm birth
      in women with abnormal vaginal flora, this effect is unlikely to be mediated
      through a reduction in the incidence of histologic chorioamnionitis. The
      relatively small size of the groups, however, does not allow us to rule out a
      real effect, especially given the lower rate of membrane inflammation observed in
      the clindamycin group. LEVEL OF EVIDENCE: I.

PMID- 16582125
TI  - First-trimester combined screening for Down syndrome and other fetal anomalies.
AB  - OBJECTIVE: This study assessed fetal outcomes for pregnancies identified at
      increased risk for Down syndrome by first-trimester combined ultrasound
      examination and maternal serum biochemistry screening. METHODS: First-trimester
      combined screening data were obtained from ultrasound clinics across Western
      Australia between August 2001 and October 2003. Prenatal screening data were
      linked with pregnancy outcome information held in state health database registers
      using probabilistic record-linkage techniques. RESULTS: In 50 of the 60
      pregnancies affected by Down syndrome, the adjusted risk was greater than 1 in
      300, providing a detection rate of 83% (95% confidence interval [CI] 74-93%).
      Among all women screened (n = 22,280), 827 had increased risk results but did not
      have a Down syndrome pregnancy, representing a false-positive rate of 3.7% (95%
      CI 3.5-3.9%). Ten cases of Down syndrome were detected among women considered not
      at increased risk, consistent with a false-negative rate of 1 in 2,227. First
      trimester combined screening reduced the number of Down syndrome births by 50 in
      22,280 (2.24 cases per 1,000 births), which represents the detection of one case
      of fetal Down syndrome for every 446 women screened. Furthermore, 25% of
      pregnancies with other birth defects occurred among those identified at increased
      risk of Down syndrome, and 1 in 8 pregnancies at increased risk were found to
      have a significant chromosomal or structural defect. CONCLUSION: First-trimester
      combined screening in Western Australia detected 83% (95% CI 74-93%) of Down
      syndrome pregnancies at a 3.7% (95% CI 3.5-3.9%) false-positive rate. LEVEL OF
      EVIDENCE: II-2.

PMID- 16582127
TI  - Maternal and paternal influences on length of pregnancy.
AB  - OBJECTIVE: Biological evidence suggests that both mother and fetus are involved
      in triggering a normal delivery. A tendency of a child to have a gestational age
      at birth similar to the father's could represent the effect of genes passed from
      the father to the fetus. Similar tendencies between mother and child could
      represent maternal genes passed to the fetus, as well as genes to the mother
      received from the grandmother that affect a woman's capacity to carry a
      pregnancy. METHODS: The Medical Birth Registry of Norway contains data on all
      births in Norway from 1967 onward. We identified 77,452 pairs of boys and girls
      born at term who later became parents and linked their birth data to the birth
      records for their first child. RESULTS: Gestational age of the child at birth
      increased on average 0.58 days for each additional week in the father's
      gestational age (95% confidence interval 0.48-0.67) and 1.22 days for each
      additional week in the mother's gestational age (1.21-1.32). Gestational age was,
      however, 0.65 days reduced for each additional kilogram in the father's birth
      weight, presumably due to more rapid growth of the fetus triggering delivery.
      CONCLUSION: Initiation of delivery has a fetal component that is heritable
      (passed from father and mother to child) and an additional maternal component
      that is also heritable. In addition, a more rapid rate of fetal growth appears to
      trigger delivery at earlier gestation. LEVEL OF EVIDENCE: II-2.

PMID- 16582126
TI  - Fetal pyelectasis: does fetal gender modify the risk of major trisomies?
AB  - OBJECTIVE: Several studies have noted an increased prevalence of pyelectasis in
      male fetuses. It is speculated that pyelectasis represents a normal physiologic
      variant in males, whereas its presence in females indicates an increased risk of
      chromosomal abnormalities. Thus, we sought to investigate the association between
      fetal gender and the risk of major trisomies in fetuses with pyelectasis.
      METHODS: Retrospective analysis of a Genzyme Genetics amniocentesis database
      (1995 to 2004) was performed. Specimens obtained after an ultrasonographic
      finding of pyelectasis were eligible for analysis. The prevalence of major
      trisomies (trisomy 13, 18, or 21) in male and female fetuses with pyelectasis was
      compared using binomial distribution. RESULTS: A total of 760,495 amniocentesis
      specimens were analyzed. Fetal pyelectasis was reported in 671 cases. A male
      predominance, with a male-to-female ratio of 2.14:1 (457 compared with 214) was
      statistically significant (P < .001). A major trisomy was detected in 26 male
      fetuses (5.7%): 18 cases of trisomy 21, 2 cases of trisomy 18, and 6 cases of
      trisomy 13. Nine female fetuses had a major trisomy (4.2%): 6 cases of trisomy 21
      and 3 cases of trisomy 13. There was no significant difference in the overall
      prevalence of trisomies between male and female fetuses (P = .14). CONCLUSION: We
      concur with previous studies documenting a higher prevalence of pyelectasis in
      male fetuses. In addition, our results indicate that the prevalence of major
      trisomies among fetuses with pyelectasis is unlikely to be dependent on fetal
      gender. Thus, counseling patients with regard to the genetic implications of
      fetal pyelectasis should be gender independent. LEVEL OF EVIDENCE: II-2.

PMID- 16582128
TI  - Effect of L-arginine therapy on the glomerular injury of preeclampsia: a
      randomized controlled trial.
AB  - OBJECTIVE: To assess the benefit of l-arginine, the precursor to nitric oxide, on
      blood pressure and recovery of the glomerular lesion in preeclampsia. METHODS:
      Forty-five women with preeclampsia were randomized to receive either l-arginine
      or placebo until day 10 postpartum. Primary outcome measures including mean
      arterial pressure, glomerular filtration rate, and proteinuria were assessed on
      the third and 10th days postpartum by inulin clearance and albumin-to-creatinine
      ratio. Nitric oxide, cyclic guanosine 3'5' monophosphate, endothelin-1, and
      asymmetric-dimethyl-arginine and arginine levels were assayed before delivery and
      on the third and 10th days postpartum. Healthy gravid women provided control
      values. Assuming a standard deviation of 10 mm Hg, the study was powered to
      detect a 10-mm Hg difference in mean arterial pressure (alpha .05, beta .20)
      between the study groups. RESULTS: No significant differences existed between the
      groups with preeclampsia before randomization. Compared with the gravid control
      group, women with preeclampsia exhibited significantly increased serum levels of
      endothelin-1, cyclic guanosine 3'5' monophosphate, and asymmetric-dimethyl
      arginine before delivery. Despite a significant increase in postpartum serum
      arginine levels due to treatment, no differences were found in the corresponding
      levels of nitric oxide, endothelin-1, cyclic guanosine 3'5' monophosphate, or
      asymmetric-dimethyl-arginine between the two groups with preeclampsia. Further,
      there were no significant differences in any of the primary outcome measures with
      both groups demonstrating similar levels in glomerular filtration rate and
      equivalent improvements in both blood pressure and proteinuria. CONCLUSION: Blood
      pressure and kidney function improve markedly in preeclampsia by the 10th day
      postpartum. Supplementation with l-arginine does not hasten this recovery. LEVEL
      OF EVIDENCE: I.

PMID- 16582129
TI  - Serum-soluble CD40 ligand in normal pregnancy and in preeclampsia.
AB  - OBJECTIVE: Soluble CD40 ligand is a transmembrane protein shed from activated
      platelets that is involved in the activation of endothelial cells. Findings that
      estradiol (E2) has an inhibitory effect on inflammation and platelet function and
      that serum E2 levels are low in women with preeclampsia prompted us to
      investigate the association between soluble CD40 ligand and serum E2 levels in
      normal pregnancy and in preeclampsia. METHODS: A case-control single-center
      design was used. The sample included 22 women with severe preeclampsia, 22
      matched normotensive pregnant women, and 22 nonpregnant women. Enzyme immunoassay
      was used to measure soluble CD40 ligand. RESULTS: Significantly higher levels of
      soluble CD40 ligand were detected in the nonpregnant women (23,767 +/- 15,637
      pg/mL) and in the women with preeclampsia (21,025 +/- 45,386 pg/mL) than in the
      normotensive pregnant women (8,292 +/- 5,926 pg/mL) (P = .026). No significant
      correlation between soluble CD40 ligand levels and E2 levels was observed.
      CONCLUSION: The higher levels of soluble CD40 ligand detected in women with
      preeclampsia may indicate an exaggerated activation of platelets and endothelial
      cells. LEVEL OF EVIDENCE: II-2.

PMID- 16582130
TI  - Factors related to successful misoprostol treatment for early pregnancy failure.
AB  - OBJECTIVE: To identify potential predictors for treatment success in medical
      management with misoprostol for early pregnancy failure. METHODS: We conducted a
      planned secondary analysis of data from a multicenter trial that compared medical
      and surgical management of early pregnancy failure. Medical management consisted
      of misoprostol 800 mug vaginally on study day 1, with a repeat dose if indicated
      on day 3. Women returned on days 3 and 15, and a telephone interview was
      conducted on day 30. Failure was defined as suction aspiration for any reason
      within 30 days. Demographic, historical, and outcome variables were included in
      univariable analyses of success. Multivariable analyses were conducted using
      clinical site, gestational age, and variables for which the univariable analysis
      resulted in a P < .1 to determine predictors of overall treatment success and
      first-dose success. RESULTS: Of the 491 women who received misoprostol, 485 met
      the criteria for this secondary analysis. Lower abdominal pain or vaginal
      bleeding within the last 24 hours, Rh-negative blood type, and nulliparity were
      predictive of overall success. However, only vaginal bleeding within the last 24
      hours and parity of 0 or 1 were predictive of first-dose success. Overall success
      exceeds 92% in women who have localized abdominal pain within the last 24 hours,
      Rh-negative blood type, or the combination of vaginal bleeding in the past 24
      hours and nulliparity. CONCLUSION: Misoprostol treatment for early pregnancy
      failure is highly successful in select women, primarily those with active
      bleeding and nulliparity. Clinicians and patients should be aware of these
      differences when considering misoprostol treatment. LEVEL OF EVIDENCE: II-2.

PMID- 16582132
TI  - The genetics of uterine leiomyomata: what clinicians need to know.
AB  - The genetics of many complex diseases, including hypertension, diabetes, and
      asthma, are receiving intense investigation and beginning to have therapeutic
      relevance. Family medical history can be a critical source of information for
      providing optimal patient care. For gynecologists, knowledge of cancer
      susceptibility genes such as BRCA1 and BRCA2 and the genetic syndrome hereditary
      nonpolyposis colorectal cancer (Lynch syndrome II) affects how patients are
      screened for ovarian and endometrial cancers. Similarly, identification of
      mutations in the fumarate hydratase (FH) gene that lead to a syndrome called
      hereditary leiomyomatosis and renal cell carcinoma (HLRCC) will impact screening
      and treatment of women with uterine leiomyomas. Hereditary leiomyomatosis and
      renal cell carcinoma syndrome is particularly relevant to clinicians and patients
      because of the resulting increased risk of malignant disease for both the
      affected woman and her family. The goals of this article are to summarize the
      evolving genetic information concerning uterine leiomyomas, including hereditary
      leiomyomatosis and renal cell carcinoma syndrome, and to discuss the clinical
      importance of these findings. The current role of family medical history and
      future implications of genes relevant to leiomyoma biology will be reviewed.

PMID- 16582131
TI  - The "costs" of urinary incontinence for women.
AB  - OBJECTIVE: To estimate costs of routine care for female urinary incontinence,
      health-related quality of life, and willingness to pay for incontinence
      improvement. METHODS: In a cross-sectional study at 5 U.S. sites, 293 incontinent
      women quantified supplies, laundry, and dry cleaning specifically for
      incontinence. Costs were calculated by multiplying resources used by national
      resource costs and presented in 2005 United States dollars (2005). Health-related
      quality of life was estimated with the Health Utilities Index. Participants
      estimated willingness to pay for 25-100% improvement in incontinence. Potential
      predictors of these outcomes were examined using multivariable linear regression.
      RESULTS: Mean age was 56 +/- 11 years; participants were racially diverse and had
      a broad range of incontinence severity. Nearly 90% reported incontinence-related
      costs. Median weekly cost (25%, 75% interquartile range) increased from 0.37
      dollars (0, 4 dollars) for slight to 10.98 dollars (4, 21 dollars) for very
      severe incontinence. Costs increased with incontinence severity (P < .001). Costs
      were 2.4-fold higher for African American compared with white women (P < .001)
      and 65% higher for women with urge compared with those having stress incontinence
      (P < .001). More frequent incontinence was associated with lower Health Utilities
      Index score (mean 0.90 +/- 0.11 for weekly and 0.81 +/- 0.21 for daily
      incontinence; P = .02). Women were willing to pay a mean of 70 dollars +/- 64
      dollars per month for complete resolution of incontinence, and willingness to pay
      increased with income and greater expected benefit. CONCLUSION: Women with severe
      urinary incontinence pay 900 dollars annually for incontinence routine care, and
      incontinence is associated with a significant decrement in health-related quality
      of life. Effective incontinence treatment may decrease costs and improve quality
      of life. LEVEL OF EVIDENCE: III.

PMID- 16582133
TI  - House calls at 30,000 feet.

PMID- 16582135
TI  - Tipranavir (Aptivus) for HIV.

PMID- 16582134
TI  - Placenta previa, placenta accreta, and vasa previa.
AB  - Placenta previa, placenta accreta, and vasa previa are important causes of
      bleeding in the second half of pregnancy and in labor. Risk factors for placenta
      previa include prior cesarean delivery, pregnancy termination, intrauterine
      surgery, smoking, multifetal gestation, increasing parity, and maternal age. The
      diagnostic modality of choice for placenta previa is transvaginal
      ultrasonography, and women with a complete placenta previa should be delivered by
      cesarean. Small studies suggest that, when the placenta to cervical os distance
      is greater than 2 cm, women may safely have a vaginal delivery. Regional
      anesthesia for cesarean delivery in women with placenta previa is safe. Delivery
      should take place at an institution with adequate blood banking facilities. The
      incidence of placenta accreta is rising, primarily because of the rise in
      cesarean delivery rates. This condition can be associated with massive blood loss
      at delivery. Prenatal diagnosis by imaging, followed by planning of peripartum
      management by a multidisciplinary team, may help reduce morbidity and mortality.
      Women known to have placenta accreta should be delivered by cesarean, and no
      attempt should be made to separate the placenta at the time of delivery. The
      majority of women with significant degrees of placenta accreta will require a
      hysterectomy. Although successful conservative management has been described,
      there are currently insufficient data to recommend this approach to management
      routinely. Vasa previa carries a risk of fetal exsanguination and death when the
      membranes rupture. The condition can be diagnosed prenatally by ultrasound
      examination. Good outcomes depend on prenatal diagnosis and cesarean delivery
      before the membranes rupture.

PMID- 16582136
TI  - Montelukast (Singulair) for perennial allergic rhinitis.

PMID- 16582137
TI  - Ambien CR for insomnia.

PMID- 16582138
TI  - Drugs in the elderly.

PMID- 16582139
TI  - ACOG Practice Bulletin number 65: management of endometrial cancer.

PMID- 16582140
TI  - Assisted reproductive technology and pregnancy outcome.

PMID- 16582141
TI  - Assisted reproductive technology and pregnancy outcome.

PMID- 16582142
TI  - ACOG Practice Bulletin. Episiotomy. Clinical Management Guidelines for
      Obstetrician-Gynecologists. Number 71, April 2006.

PMID- 16582143
TI  - ACOG Committee Opinion. Evaluation and management of abnormal cervical cytology
      and histology in the adolescent. Number 330, April 2006.
AB  - The management of abnormal cervical cytology in adolescents differs from that for
      the adult population in many cases. Certain characteristics of adolescents may
      warrant special management considerations. It is important to avoid aggressive
      management of benign lesions in adolescents because most cervical intraepithelial
      neoplasia grades 1 and 2 regress. Surgical excision or destruction of cervical
      tissue in a nulliparous adolescent may be detrimental to future fertility and
      cervical competency. Care should be given to minimize destruction of normal
      cervical tissue whenever possible. A compliant, health-conscious adolescent may
      be adequately served with observation in many situations.

PMID- 16582144
TI  - ACOG Committee Opinion. Safe use of medication. Number 331, April 2006.
AB  - Medication use errors are the largest single source of preventable adverse
      events. To minimize the risk of medication use errors, obstetrician-gynecologists
      should focus on several elements of medication order writing, such as the
      appropriate use of decimals and zeros, standard abbreviations, and assuring
      legibility. Additionally, it is important to assist the patient in understanding
      the medical condition for which a medication is prescribed. Focusing on elements
      that may prevent prescription errors and helping patients understand how to use
      prescribed medication properly may help lower the occurrence of medication use
      errors.

PMID- 16582145
TI  - ACOG (American College of Obstetricians and Gynecologists) 54th Annual Clinical
      Meeting, May 6-10, 2006, Washington, DC, USA. Abstracts.

PMID- 16582404
TI  - Strategies for the prevention of iron deficiency anaemia in children.

PMID- 16582405
TI  - Profile and factors determining outcome in a cohort of cystic fibrosis patients
      seen at the Aga Khan University Hospital, Karachi, Pakistan.
AB  - Cystic fibrosis is the most common potentially lethal autosomal recessive,
      genetic disease associated with pulmonary and pancreatic insufficiency. It is
      caused by variations in the CFTR (cystic fibrosis transmembrane regulator) gene.
      The most common mutation in the CFTR gene designated DeltaF508, is found in only
      33 per cent of CF patients in Pakistan. The variability in presentation and
      clinical severity of disease may be a function of genotypic-phenotypic factors.
      Our aim was to attempt to define the disease in this region and to lay the ground
      work for future mutational analysis. This study was a retrospective chart review
      was conducted to identify cystic fibrosis patients seen at the Aga Khan
      University Hospital over a 10-year period. Our study identified 56 patients
      diagnosed by a pilocarpine iontophoresis sweat test. A chart review was then done
      to look at the various clinical profiles. 58.3 per cent of our patients presented
      in the first 6 months of life supporting the hypothesis that CF may be a severe
      disease in Asians with an earlier age of presentation. Most of the patients (80.6
      per cent) presented with pulmonary problems while 83.9 per cent had failure to
      thrive. The most frequently isolated pathogen was Pseudomonas aeruginosa in 87.5
      per cent of the patients tested. 70 per cent of the patients died in the first
      year of life. The clinical parameters studied suggest a severe form of CF in
      Pakistani patients and provides a foundation for future studies to define
      genotype/phenotype correlations of the specific mutations involved in Pakistani
      CF patients.

PMID- 16582406
TI  - Outcomes for vasovasostomy performed when only sperm parts are present in the
      vasal fluid.
AB  - This article reviews the outcomes for vasovasostomy (VV) when only sperm parts
      were present in the vasal fluid. Thirtyfour patients who underwent bilateral (31)
      or unilateral (3) VV had either sperm parts bilaterally or sperm parts on 1 side
      and intravasal azoospermia on the contralateral side. Two of the procedures (1
      unilateral, 1 bilateral) were repeat procedures. Patient and partner age were 42
      +/- 1.2 (range: 34-54 and 33 +/- 0.9 (range: 23-42) years, respectively. Follow
      up was 10 +/- 1.8 months. The obstructive interval was 10 +/- 0.9 (range: 4-27)
      years. The patency rate was 76% (26/34). The obstructive interval ranges for
      patent cases versus not-patent cases were 3 to 21 and 3 to 27 years,
      respectively. The obstructive interval did not differ between the patent and not
      patent groups (9 years vs 11 years, P = 0.3978). The pregnancy rate for those
      with sufficient follow-up was 35% (7/20). Of the 8 failed cases, 2 had only an
      occasional sperm head bilaterally and 1 other had an occasional sperm head on 1
      side and contralateral intravasal azoospermia. If these 3 cases were excluded,
      then the patency rate was 84% (26/31). The patency rate for VV performed when
      only sperm parts were present in the vas fluid was lower than previously reported
      patency rates with complete sperm but at least as good as most surgeons'
      experience with vasoepididymostomy. The pregnancy rate was also less than
      previously reported pregnancy rates with complete sperm. These data suggest that
      VV is indicated only when sperm parts are noted in the vasal fluid. There does
      not appear to be a threshold obstructive interval above which VE would be
      indicated in this setting. If only an occasional sperm head is noted in the vasal
      fluid, then the surgeon should consider vasoepididymostomy.

PMID- 16582407
TI  - Truncated semenogelin I binds zinc and is cleaved by prostate-specific antigen.
AB  - Semenogelins I and II are major coagulum-forming proteins in semen, and they are
      secreted mainly by the seminal vesicles. These proteins bind Zn(2+) and act as
      substrates for prostate-specific antigen and transglutaminase. A variant
      semenogelin I lacking 60 amino acids has been described that occurs in different
      populations with an allele frequency of 1%-3%. To better understand the function
      of the semenogelins in vivo, our aim was to characterize the properties of the
      variant form and compare with the wild type. Recombinant proteins were
      synthesized in insect cells. Binding of Zn(2+) was studied by titration of metal
      ions in the presence of a zinc (II) fluorophore chelator. SDS-PAGE was used to
      visualize the results of cleavage by prostate-specific antigen and cross-linking
      with transglutaminase. We found that the truncated and wild-type semenogelin
      molecules had similar Zn(2+)-binding properties (ie, a stoichiometry of at least
      9-10 mol per mol of protein and an average dissociation constant of 5 mumol/L per
      site), and they showed also similar susceptibility for degradation by prostate
      specific antigen. Furthermore, like the wild-type form, the truncated semenogelin
      I was able to serve as a substrate for transglutaminase. These findings imply
      that the studied characteristics do not depend on a well-defined tertiary
      structure, or that the deletion has no major effect on the structure responsible
      for these features.

PMID- 16582408
TI  - De novo morphogenesis of seminiferous tubules from dissociated immature rat
      testicular cells in xenografts.
AB  - Testicular development is initiated with the differentiation of Sertoli cells in
      the embryonic gonad. The aggregation of Sertoli cells is crucial for the
      generation of testicular cords and thus for the first sign of male gonadal
      development. To date, functional testicular tissue has not yet been generated in
      vitro. The objective of this study was to explore the de novo morphogenesis of
      testicular tissue from isolated postnatal rat testicular cells using a
      combination of in vitro culture and ectopic xenografting. Immature rat testicular
      cells were cultured in either a 2-dimensional (laminin-coated coverglass) or a 3
      dimensional (extracellular matrix gel) culture system. Whereas testicular cells
      cultured on laminin showed a slow morphogenetic cascade resulting in cord
      formation after about 10 days of culture, cells cultured on extracellular matrix
      gel assembled to a network of cordlike structures within several hours after
      plating and formed spherical cell aggregates at day 3. Further progression of the
      morphogenetic cascade was not obtained in either the 2- or the 3-dimensional
      culture system. In contrast, structures resembling immature testicular tissue
      were obtained after xenografting of extracellular matrix gel-enclosed spherical
      testicular cell aggregates. The grafts were vascularized and contained elongated
      seminiferous tubules. Histologic analysis revealed the presence of a basement
      membrane, a histologically normal interstitium containing putative Leydig cells,
      the establishment of tubule lumen, and the integration of few putative
      spermatogonia into the seminiferous epithelium. We conclude that immature rat
      testicular cells carry the full potential to generate all somatic components of a
      testis in xenografts, thus opening fascinating pathways to study testicular
      organogenesis.

PMID- 16582409
TI  - Proteins of the cauda epididymal fluid associated with fertility of mature dairy
      bulls.
AB  - We evaluated the relationships between proteins in cauda epididymis fluid (CEF)
      and fertility scores of dairy bulls. Fertility was expressed as the percentage
      point deviation (PD) of bull nonreturn rate from the average fertility of all
      bulls at an artificial insemination center. The number of services for each bull
      ranged from 1074 to 52 820, and PD values ranged from +7.7% to -6.6%. CEF from 20
      bulls was obtained from vasa deferentia cannulae and was separated from sperm by
      centrifugation immediately after collection. Samples were evaluated by 2
      dimensional (2-D) sodium dodecyl sulfate polyacrylamide gel electrophoresis gels
      stained with Coomassie blue, and polypeptide maps were analyzed by PDQuest
      software. Protein quantities, defined as the total integrated optical density of
      the spots, were compared between groups of high-fertility sires (n = 12; PD >or=
      0) and low-fertility sires (n = 8; PD < 0) and were also used as independent
      variables in regression analysis. Proteins were identified by capillary liquid
      chromatography-nanoelectrospray ionization-tandem mass spectrometry. An average
      of 118 spots was detected in 2-D maps of the CEF, but we were unable to
      distinguish any protein that was expressed only in high-fertility or in low
      fertility bulls. However, the amount of alpha-L-fucosidase 2 and cathepsin D was
      2.3- and 2.4-fold greater (P < .05) in high-fertility than in low-fertility
      bulls, respectively. Conversely, the intensities of 3 isoforms (24-27 kd; pl 6.3
      5.8) of prostaglandin D-synthase (PGDS) were from 3.2- to 2.2-fold greater in low
      fertility sires (P < .05). An empirical regression model established that a
      significant proportion (R(2) = 0.72; P < .0001) of the variation in fertility
      scores (PD values) was explained by the intensities of cathepsin D and 1 isoform
      of PGDS (24 kd; pl 6.3). Thus, multiple proteins present in the CEF are potential
      biomarkers of fertility in high-use, mature Holstein bulls.

PMID- 16582410
TI  - Reducing estrogen synthesis in developing boars increases testis size and total
      sperm production.
AB  - The abundant production of testicular estrogens and the presence of both ESR1 and
      ESR2 within boar testes are consistent with a role for estrogen in testicular
      development and/or function in this species. This study was aimed at determining
      the role of endogenous estrogen in the regulation of testicular development and
      function, including the effects on testis weight, histology, sperm production
      (detergent-resistant spermatid numbers), Sertoli cell numbers, and Leydig cell
      volume in the boar. Twenty-eight littermate pairs of boars were assigned to
      groups as follows: 1 boar from each pair was assigned to the control group
      (vehicle) and the other was assigned to treatment and received 0.1 mg/kg body
      weight of an aromatase enzyme inhibitor (letrozole) orally each week beginning at
      1 week of age until castration at 2, 3, 4, 5, 6, 7, or 8 months of age. Testes
      were weighed and testicular parenchyma was recovered for determination of
      histology and detergent-resistant spermatid numbers, and for determination of
      Sertoli cell number and Leydig cell volume by staining for GATA-4 and 17-alpha
      hydroxylase/17-20 lyase respectively. Testes of aromatase-inhibited boars
      initially exhibited delayed lumen formation, lower testicular weight, fewer
      detergent-resistant spermatids, and fewer Sertoli cells, but by 7 to 8 months,
      these boars had recovered and had larger testes, more detergent-resistant
      spermatids per testis, and more Sertoli cells. Total Leydig cell volume increased
      in proportion to testis size. Reducing endogenous estrogen is consistent with a
      delay in testicular maturation/puberty that allows for a longer window for the
      proliferation of Sertoli cells and maturation of Leydig cells, resulting in
      larger testes and higher spermatid production.

PMID- 16582412
TI  - Immunohistochemical localization of sperm-preserving proteins in the ram
      reproductive tract.
AB  - Previously, we reported that the addition of seminal plasma proteins before cold
      shock treatment prevents sperm membrane injury, and that 2 proteins of
      approximately 14 (P14) and 20 (P20) kDa, the main components of fraction 6
      isolated by exclusion chromatography, are responsible for this protective effect.
      The objective of the present study was to localize P14 and P20 in tissues of the
      ram reproductive tract to determine their origin. Antiserum generated against
      purified P14 and P20 reacted with proteins in seminal vesicles and vas deferens
      by Western blot analyses of protein tissue extracts. However, these antisera
      failed to detect P14 and P20 in testis, prostate, efferent ductules,
      bulbourethral glands, and epididymis (caput, corpus, and cauda).
      Immunohistochemical analyses by both indirect immunofluorescence and the avidin
      biotin complex technique confirmed that only seminal vesicles showed reactivity,
      restricted to the secretory cells, with both antibodies. Obtained results
      indicate that P14 and P20 are secreted specifically in the seminal vesicles. To
      further confirm that P14 and P20 are specifically expressed in seminal vesicles,
      we used Northern blot analyses to investigate the expression of both proteins in
      seminal vesicles and vas deferens. These assays corroborated again that P14 and
      P20 were specifically expressed in seminal vesicles. Consequently, we suggest
      referring to these 2 proteins as RSVP14 and RSVP20, respectively, according to
      their origin and molecular weight.

PMID- 16582411
TI  - Inhibin-B levels in healthy young adult men and prepubertal boys: is obesity the
      cause for the contemporary decline in sperm count because of fewer Sertoli cells?
AB  - Inhibin-B is a heterodimeric glycoprotein produced by Sertoli cells. Although
      inhibin-B levels are low when seminiferous tubules are damaged, studies in normal
      monkeys reveal that inhibin-B levels also correlate positively with Sertoli cell
      number. In this study, we measured inhibin-B levels in healthy young adult men
      aged 18-24 years and in prepubertal boys aged 5-9 years in relation to body mass
      index (BMI). Inhibin-B levels declined with increasing obesity in young adult
      men; values were 26% lower in men who were obese compared to normal-weight men.
      Sex hormone-binding globulin and total testosterone, but not free testosterone,
      were also lower with increasing BMI; serum follicle-stimulating hormone and
      luteinizing hormone levels were unaffected by obesity. In prepubertal boys, by
      contrast, inhibin-B was unaffected by obesity. We propose that reduced levels of
      inhibin-B indicate that obese men have fewer Sertoli cells than men of normal
      weight. Moreover, normal values in obese prepubertal boys suggest that the effect
      of obesity on inhibin-B is established during puberty. Finally, because each
      Sertoli cell is thought to support a finite number of germ cells, fewer Sertoli
      cells in obesity may predispose to a lower sperm count in adulthood. We speculate
      that the escalating prevalence of obesity and insulin resistance among
      adolescents might negatively influence male reproductive function for the next
      generation.

PMID- 16582414
TI  - A novel androgen receptor mutation resulting in complete androgen insensitivity
      syndrome and bilateral Leydig cell hyperplasia.
AB  - Androgens drive male secondary sexual differentiation and maturation. Mutations
      in the androgen receptor (AR) gene cause a broad spectrum of abnormal phenotypes
      in humans, ranging from mild through partial to complete androgen insensitivity.
      We have analyzed the AR gene by using denaturing high-performance liquid
      chromatography (DHPLC) and direct sequencing and have studied gonads
      histologically in a familial case of complete androgen insensitivity syndrome.
      Sequence analysis of the AR gene showed a novel C2578T missense mutation,
      resulting in the replacement of a highly conserved leucine residue with
      phenylalanine (L859F) in ligand-binding domain of the receptor. The residue L859,
      located in helix 10 of the androgen receptor, plays a significant role in overall
      architecture of ligand-binding pocket. The mutation was absent from the father,
      normal brother of the patients, and 100 normal males recruited in this study as
      controls. The inheritance of the mutation in the family clearly shows that C2578T
      is the underlying mutation for the eventual phenotype in the patients. Histology
      of patient's gonads showed Leydig cell hyperplasia, with a few or no
      spermatogonium. It is thought that AR gene mutations result in hormonal
      imbalance, resulting in the high levels of luteinizing hormone (LH) and
      ultimately Leydig cell hyperplasia or tumor formation. In the present study, we
      have reported a rare familial case of Leydig cell hyperplasia despite
      consistently normal LH levels. The finding will help in giving counseling to this
      family and prevent the transmission of the mutated X chromosome to the coming
      generations.

PMID- 16582413
TI  - Testis-specific lactate dehydrogenase (LDH-C4; Ldh3) in murine oocytes and
      preimplantation embryos.
AB  - LDH-C(4) (Ldh3) is a member of the lactate dehydrogenase family of isozymes that
      catalyze the terminal reaction in the glycolytic pathway. In mammals, 3 genes,
      ldha, ldhb, and Ldhc, encode the subunits that assemble into catalytically active
      homo- and heterotetramers. Differential expression of these genes determines the
      lactate dehydrogenase (LDH) isozyme composition of tissues, and, as is well
      known, A subunits predominate in skeletal muscle and B subunits are abundantly
      produced in brain and heart, with the Ldh2 isozyme the most abundant form in
      oocytes. The C peptide can be detected first in pachytene spermatocytes and
      constitutes the primary LDH of spermatozoa. Originally the Ldhc gene (Ldh3 in
      terminology applied to murine cells) was considered to be testis specific on the
      basis of immunochemical, enzymatic, and molecular analyses. Here we report the
      detection of this isozyme in the murine oocyte and early embryo. Our results
      indicate that Ldh3 mRNA is transcribed in oocytes and cannot be detected in
      fertilized eggs. Ldh3 protein, however, persists to the blastocyst stage of
      embryonic development localizing mainly to the cortex region of oocytes, eggs,
      zygotes, and embryonic blastomeres.

PMID- 16582415
TI  - Dose-response relationship between testosterone and erectile function: evidence
      for the existence of a critical threshold.
AB  - Androgens play an important role in erectile function. However, the dose-response
      relationship between plasma testosterone levels and penile erection remains
      unclear. Intact (sham operated) or bilaterally orchiectomized, mature male
      Sprague-Dawley rats were used. Two weeks after surgery, rats were infused
      continuously with either vehicle (polyethyleneglycol) or varying doses of
      testosterone (44, 88, 220, or 440 mug/day) for 14 days using subcutaneous osmotic
      infusion pumps (study 1). In a separate study, 4 weeks after surgery, rats were
      infused with a lower range of testosterone doses (11, 22, or 44 mug/day) for 14
      days (study 2). In the first study, intact rats had a mean plasma testosterone
      concentration of 0.56 +/- 0.12 ng/mL ( approximately 1.9 nM), as determined by
      standard radioimmunoassay. In the second study, a more sensitive enzyme-linked
      immunoassay was used to measure the lower testosterone levels. Using this assay,
      intact rats had a mean plasma testosterone concentration of 2.02 +/- 0.59 ng/mL.
      Intracavernosal pressure measurements indicated that orchiectomy resulted in a
      significant reduction in erectile function, when compared to intact animals,
      whereas testosterone infusion restored erectile function to varying degrees.
      Erectile function was maintained by a wide range of systemic testosterone levels
      as low as 10%-12% of normal physiological plasma concentrations. Below these
      concentrations, erectile function was significantly and positively correlated
      with testosterone plasma levels in a dose-dependent manner. Interestingly,
      prostate tissue mass was positively correlated to plasma testosterone levels
      across all concentrations examined. Protein expression of neural nitric oxide
      synthase (nNOS) and phosphodiesterase type 5 (PDE 5) was reduced in penile tissue
      from orchiectomized animals and increased in testosterone-infused animals, as
      assessed by Western blot analyses. We suggest that testosterone at levels
      approaching one-tenth normal physiological plasma concentration may represent a
      threshold value, below which erectile function declines in a dose-dependent
      fashion. However, different androgen-dependent tissues may exhibit varying
      sensitivities to circulating testosterone with regard to growth and function.

PMID- 16582416
TI  - Two-step cluster procedure after principal component analysis identifies sperm
      subpopulations in canine ejaculates and its relation to cryoresistance.
AB  - A 2-step clustering procedure, using indexes derived from principal component
      analysis, was used to disclose sperm subpopulations within the canine ejaculate
      and its relationship to sperm cryoresistance. Semen from 4 dogs was frozen-thawed
      by a standard protocol: before freezing, computer-assisted sperm analysis of
      motility and morphometry were performed; after thawing, motility analysis was
      performed again; and cryoresistance was estimated as the percent changes in
      progressive motility and sperm velocities after thawing. We used indexes derived
      from principal component analysis (sperm velocity index [SVI] and sperm motility
      index [SMI]) and the SPSS 2-step cluster method to disclose sperm subpopulations.
      The 2-step clustering procedure revealed the existence of 6 subpopulations.
      Subpopulations 4 and 6 were characterized by high values of both SVI (>200
      arbitrary units) and SMI (>90 arbitrary units), subpopulations 2 and 3 were
      characterized by medium values (SVI 100 to 130; and SMI 30 to 40), and
      subpopulations 1 and 5 were characterized by low values (SVI < 100; SMI < 30).
      The distribution of sperm subpopulations was completely different among dogs.
      Four sperm subpopulations based in morphometric parameters of the sperm head and
      midpiece were revealed. Models including SVI and SMI indexes explained
      curvilinear velocity (R(2) = 0.997; P < .001), straight-line velocity (R(2) =
      0.98; P < .001), and average velocity (R(2) = 0.99; P < .0001) postthaw.

PMID- 16582417
TI  - SAMMA induces premature human acrosomal loss by Ca2+ signaling dysregulation.
AB  - SAMMA is licensed for development as a contraceptive microbicide. Understanding
      mechanisms of its biological activity is prerequisite to designing more active
      second generation products. This study examined Ca(2+) involvement in SAMMA
      induced premature acrosomal loss (SAL) in noncapacitated human spermatozoa. SAMMA
      causes acrosomal loss (AL) in a dose-dependent manner (ED(50) = 0.25 microg/mL).
      SAL requires extracellular Ca(2+) (ED(50) = 85 microM). SAL is inhibited by
      verapamil (nonspecific voltage-dependent Ca(2+) channel blocker; IC(50) = 0.4
      microM), diphenylhydantoin and NiCl(2) (T-type [Ca(v)3.x] channel blockers;
      IC(50) 210 microM and 75 microM, respectively). Verapamil blockade of L-type
      (Ca(v)1.x) channels is use-dependent; activated channels are more sensitive to
      inhibition. However, verapamil inhibition of SAL does not increase after repeated
      SAMMA stimulation. SAL is unaffected by 10 microM nifedipine (selective L-type
      channel blocker). This contrasts to 40% inhibition (P < .001) of AL induced by 1
      microM thapsigargin (Ca(2+)-ATPase inhibitor; releases intracellular Ca(2+)
      stores, promotes capacitative Ca(2+) entry). SAL is unaffected by 1 microM BAPTA
      AM (intracellular Ca(2+) chelator), and 50 microM 2-APB (blocks InsP3 receptors
      and store-operated channels). This contrasts with thapsigargin-induced AL,
      inhibited nearly 65% by BAPTA-AM (P < .005) and 91% by 2-APB (P, .001). The
      results suggest that SAL is mediated by Ca(2+) entry through channels
      pharmacologically similar to the T-type (Ca(v)3.2) class. This process appears
      distinct from that caused by physiological stimuli such as progesterone or zona
      pellucida-derived proteins. SAMMA's contraceptive activity may be caused by
      induction of premature AL through dysregulation of Ca(2+) signaling.

PMID- 16582418
TI  - Appearance of hyaluronan binding protein 1 proprotein in pachytene spermatocytes
      and round spermatids correlates with spermatogenesis.
AB  - The proprotein form of hyaluronan binding protein 1 (HABP1) has been reported to
      be present in the pachytene spermatocytes and the round spermatids of the adult
      testis. To explore the role of HABP1 proprotein in spermatogenesis, its
      expression in the testes of adult rats was compared with that in the testes of
      developing rats and that in the testes of adult rats that received estriadiol to
      halt spermatogenesis. Immunoblotting revealed that the mature form of HABP1 was
      consistently present in the testis, but its precursor form was not found in the
      testis of animals aged 7, 14, 21, and 28 days. However, immunohistochemical
      analysis revealed the presence of the proprotein form in the pachytene
      spermatocytes and the round spermatids of testes from rats aged 21 and the 28
      days, the appearance of which correlated well with the appearance of these cells
      during spermatogenesis. Reverse-transcriptase polymerase chain reaction revealed
      transcriptional upregulation of HABP1 in the testes of adult rats, compared with
      the testes of developing rats. Finally, loss of HABP1 proprotein expression from
      the pachytene spermatocytes and round spermatids was observed in the testes from
      rats in which spermatogenesis was arrested. Collectively, these findings
      demonstrate the appearance of HABP1 proprotein in the pachytene spermatocytes and
      the round spermatids during the initial stages of postnatal testis development
      and suggest that this expression may be crucial for spermatogenesis.

PMID- 16582419
TI  - Changes in membrane lipid order with capacitation in rhesus macaque (Macaca
      mulatta) spermatozoa.
AB  - Lipophilic fluorescent dye merocyanine 540 is believed to stain cell membranes
      with increasing affinity as the lipid components become more disordered and has
      been associated with changes in membrane fluidity. The aim of this study was to
      determine whether membrane lipid disorder is associated with capacitation of
      macaque spermatozoa. To induce capacitation, spermatozoa from 5 rhesus macaques
      were incubated at 37 degrees C (5% CO(2) in air) for 2 hours in a modified
      Biggers-Whitten-Whittingham medium containing 30 mg/mL bovine serum albumin and
      36 mmol/L NaHCO(3). Caffeine (1 mmol/L) and dbcAMP (1.2 mmol/L) were added to the
      medium, and incubation was performed for an additional 30 minutes. Sperm motility
      was determined by computer-assisted sperm analysis, and membrane lipid order and
      sperm viability was determined by flow cytometry with merocyanine (2.7
      micromol/L) and Yo-Pro-1 (25 nmol/L), respectively. Tyrosine phosphorylation of
      proteins in sperm tail was immunohistochemically examined by means of anti
      phosphotyrosine (alpha-PY; clone 4G10). Capacitation resulted in a significant
      increase in the amplitude of lateral head displacement and beat cross frequency
      (P < .005) and a significant decrease in linearity and straightness in
      capacitated spermatozoa (P < .005), compared with control spermatozoa, which
      suggests the expression of hyperactivated motility. Animals in which capacitation
      was induced had a significant increase in the number of spermatozoa showing
      tyrosine phosphorylation of tail proteins (P < .0001) and a significant increase
      in the intensity of merocyanine fluorescence (P < .0001), compared with control
      animals. The observed decrease in membrane lipid order after capacitation was
      induced was not associated with surface exposure of phosphatidylserine, as
      determined by flow cytometry with annexin V-Alexa Fluor 488. Merocyanine may be a
      useful tool for investigating the role of the plasma membrane on capacitation and
      other cytotoxic events in macaque spermatozoa.

PMID- 16582420
TI  - Protein palmitoylation by a family of DHHC protein S-acyltransferases.
AB  - Protein palmitoylation refers to the posttranslational addition of a 16 carbon
      fatty acid to the side chain of cysteine, forming a thioester linkage. This acyl
      modification is readily reversible, providing a potential regulatory mechanism to
      mediate protein-membrane interactions and subcellular trafficking of proteins.
      The mechanism that underlies the transfer of palmitate or other long-chain fatty
      acids to protein was uncovered through genetic screens in yeast. Two related S
      palmitoyltransferases were discovered. Erf2 palmitoylates yeast Ras proteins,
      whereas Akr1 modifies the yeast casein kinase, Yck2. Erf2 and Akr1 share a common
      sequence referred to as a DHHC (aspartate-histidine-histidine-cysteine) domain.
      Numerous genes encoding DHHC domain proteins are found in all eukaryotic genome
      databases. Mounting evidence is consistent with this signature motif playing a
      direct role in protein acyltransferase (PAT) reactions, although many questions
      remain. This review presents the genetic and biochemical evidence for the PAT
      activity of DHHC proteins and discusses the mechanism of protein-mediated
      palmitoylation.

PMID- 16582421
TI  - Formation of Nepsilon-(succinyl)lysine in vivo: a novel marker for
      docosahexaenoic acid-derived protein modification.
AB  - Free radical-catalyzed peroxidation of docosahexaenoic acid (DHA, C22:6/omega-3)
      generates various lipid peroxidation products that covalently modify biomolecules
      such as proteins. Under a free radical-generating system, DHA significantly
      modified lysine residues in bovine serum albumin. Upon incubation of oxidized DHA
      with an amino-compound pyridoxamine or a lysine-containing peptide, N-propanoyl
      and N-succinyl adducts were determined to be the major modification products. The
      hydroperoxide levels in the oxidized DHA closely reflected the formation of the
      N(epsilon)-(succinyl)lysine (SUL) upon reaction with the peptide, indicating that
      the hydroperoxides of DHA represent a potential pathway for the formation of SUL.
      To detect the DHA-derived protein modification in vivo, we developed a monoclonal
      antibody (mAb2B12) specific to SUL and found that the antibody specifically
      reacts with the SUL moiety. The formation of SUL was then immunochemically
      demonstrated in the liver of mice fed with DHA followed by intraperitoneal
      injection of carbon tetrachloride (CCl(4)), a hepatic lipid peroxidation model.
      Immunoreactive materials with mAb2B12 were observed in the DHA + CCl(4) group,
      but were not significant in the control, DHA-alone, and CCl(4)-alone groups.
      These data suggest that the formation of DHA-derived adducts such as SUL may be
      implicated in the oxidative damage observed in DHA-enriched tissues.

PMID- 16582422
TI  - Endogenous transforming growth factor-beta receptor-mediated Smad signaling
      complexes analyzed by mass spectrometry.
AB  - ASmad proteins are the central feature of the transforming growth factor-beta
      (TGF-beta) intracellular signaling cascade. They function by carrying signals
      from the cell surface to the nucleus through the formation of a series of
      signaling complexes. Changes in Smad proteins and their complexes upon treatment
      with TGF-beta were studied in mink lung epithelial (Mv1Lu) cell cultures. A time
      course of incubation with TGF-beta was carried out to determine the peak of
      appearance of phosphorylated Smad2. Immobilized monoclonal antibody against Smad2
      was then used to isolate the naturally occurring complexes. Three strategies were
      used to identify changes in proteins partnering with Smad2: separation by one
      dimensional SDS-PAGE followed by MALDI peptide mass fingerprinting, cleavable
      ICAT labeling of the protein mixtures analyzed by LC-MS/MS, and nano-LC followed
      by MALDI MS TOF/TOF. Smad2 forms complexes with many other polypeptides both in
      the presence and absence of TGF-beta. Some of the classes of proteins identified
      include: transcription regulators, proteins of the cytoskeletal scaffold and
      other tethering proteins, motility proteins, proteins involved in transport
      between the cytoplasm and nucleus, and a group of membrane adaptor proteins.
      Although some of these have been reported in the literature, most have not been
      reported previously. This work expands the repertoire of proteins known to
      participate in the TGF-beta signal transduction processes.

PMID- 16582424
TI  - Telomeric silencing of an open reading frame in Saccharomyces cerevisiae.
AB  - The endmost chromosome I ORF is silenced by a natural telomere position effect.
      YAR073W/IMD1 was found to be transcribed at much higher levels in sir3 mutants
      and when its adjacent telomere was removed from it. These results suggest that
      telomeres play a role in silencing actual genes.

PMID- 16582426
TI  - Crosslinks rather than strand breaks determine access to ancient DNA sequences
      from frozen sediments.
AB  - Diagenesis was studied in DNA obtained from Siberian permafrost (permanently
      frozen soil) ranging from 10,000 to 400,000 years in age. Despite optimal
      preservation conditions, we found the sedimentary DNA to be severely modified by
      interstrand crosslinks; single- and double-stranded breaks; and freely exposed
      sugar, phosphate, and hydroxyl groups. Intriguingly, interstrand crosslinks were
      found to accumulate approximately 100 times faster than single-stranded breaks,
      suggesting that crosslinking rather than depurination is the primary limiting
      factor for ancient DNA amplification under frozen conditions. The results
      question the reliability of the commonly used models relying on depurination
      kinetics for predicting the long-term survival of DNA under permafrost conditions
      and suggest that new strategies for repair of ancient DNA must be considered if
      the yield of amplifiable DNA from permafrost sediments is to be significantly
      increased. Using the obtained rate constant for interstrand crosslinks the
      maximal survival time of amplifiable 120-bp fragments of bacterial 16S ribosomal
      DNA was estimated to be approximately 400,000 years. Additionally, a clear
      relationship was found between DNA damage and sample age, contradicting
      previously raised concerns about the possible leaching of free DNA molecules
      between permafrost layers.

PMID- 16582425
TI  - Genomic analysis of the Opi- phenotype.
AB  - Most of the phospholipid biosynthetic genes of Saccharomyces cerevisiae are
      coordinately regulated in response to inositol and choline. Inositol affects the
      intracellular levels of phosphatidic acid (PA). Opi1p is a repressor of the
      phospholipid biosynthetic genes and specifically binds PA in the endoplasmic
      reticulum. In the presence of inositol, PA levels decrease, releasing Opi1p into
      the nucleus where it represses transcription. The opi1 mutant overproduces and
      excretes inositol into the growth medium in the absence of inositol and choline
      (Opi(-) phenotype). To better understand the mechanism of Opi1p repression, the
      viable yeast deletion set was screened to identify Opi(-) mutants. In total, 89
      Opi(-) mutants were identified, of which 7 were previously known to have the Opi(
      ) phenotype. The Opi(-) mutant collection included genes with roles in
      phospholipid biosynthesis, transcription, protein processing/synthesis, and
      protein trafficking. Included in this set were all nonessential components of the
      NuA4 HAT complex and six proteins in the Rpd3p-Sin3p HDAC complex. It has
      previously been shown that defects in phosphatidylcholine synthesis (cho2 and
      opi3) yield the Opi(-) phenotype because of a buildup of PA. However, in this
      case the Opi(-) phenotype is conditional because PA can be shuttled through a
      salvage pathway (Kennedy pathway) by adding choline to the growth medium. Seven
      new mutants present in the Opi(-) collection (fun26, kex1, nup84, tps1, mrpl38,
      mrpl49, and opi10/yol032w) were also suppressed by choline, suggesting that these
      affect PC synthesis. Regulation in response to inositol is also coordinated with
      the unfolded protein response (UPR). Consistent with this, several Opi(-) mutants
      were found to affect the UPR (yhi9, ede1, and vps74).

PMID- 16582427
TI  - Estimating the genomewide rate of adaptive protein evolution in Drosophila.
AB  - When polymorphism and divergence data are available for multiple loci, extended
      forms of the McDonald-Kreitman test can be used to estimate the average
      proportion of the amino acid divergence due to adaptive evolution--a statistic
      denoted alpha. But such tests are subject to many biases. Most serious is the
      possibility that high estimates of alpha reflect demographic changes rather than
      adaptive substitution. Testing for between-locus variation in alpha is one
      possible way of distinguishing between demography and selection. However, such
      tests have yielded contradictory results, and their efficacy is unclear.
      Estimates of alpha from the same model organisms have also varied widely. This
      study clarifies the reasons for these discrepancies, identifying several method
      specific biases in widely used estimators and assessing the power of the methods.
      As part of this process, a new maximum-likelihood estimator is introduced. This
      estimator is applied to a newly compiled data set of 115 genes from Drosophila
      simulans, each with each orthologs from D. melanogaster and D. yakuba. In this
      way, it is estimated that alpha approximately 0.4+/-0.1, a value that does not
      vary substantially between different loci or over different periods of
      divergence. The implications of these results are discussed.

PMID- 16582428
TI  - N-terminal domain of yeast Hsp104 chaperone is dispensable for thermotolerance
      and prion propagation but necessary for curing prions by Hsp104 overexpression.
AB  - Hsp104 is a hexameric protein chaperone that resolubilizes stress-damaged
      proteins from aggregates. Hsp104 promotes [PSI(+)] prion propagation by breaking
      prion aggregates, which propagate as amyloid fibers, into more numerous prion
      "seeds." Inactivating Hsp104 cures cells of [PSI(+)] and other amyloid-like yeast
      prions. Overexpressing Hsp104 also eliminates [PSI(+)], presumably by completely
      resolubilizing prion aggregates. Inexplicably, however, excess Hsp104 does not
      cure the other prions. Here we identify missense mutations in Hsp104's amino
      terminal domain (NTD), which is conserved among Hsp100 proteins but whose
      function is unknown, that improve [PSI(+)] propagation. Hsp104Delta147,
      engineered to lack the NTD, supported [PSI(+)] and functioned normally in
      thermotolerance and protein disaggregation. Hsp104Delta147 failed to cure
      [PSI(+)] when overexpressed, however, implying that excess Hsp104 does not
      eliminate [PSI(+)] by direct dissolution of prion aggregates. Curing of [PSI(+)]
      by overexpressing catalytically inactive Hsp104 (Hsp104KT), which interferes with
      endogenous Hsp104, did not require the NTD. We further found that Hsp104 mutants
      defective in threading peptides through the hexamer pore had reduced ability to
      support [PSI(+)] in proportion to protein resolubilization defects, suggesting
      that [PSI(+)] propagation depends on this threading and that Hsp104 "breaks"
      prion aggregates by extracting protein monomers from the amyloid fibers.

PMID- 16582430
TI  - Sex-dependent resistance to the pathogenic fungus Cryptococcus neoformans.
AB  - Sex differences occur in most species and affect a variety of biological traits
      including morphology, behavior, and life history. The nematode Caenorhabditis
      elegans exists as a population of self-fertile hermaphrodites with occasional
      males, which differ anatomically and behaviorally from hermaphrodites. Here we
      show that male C. elegans also differ from hermaphrodites in their susceptibility
      to a fungal pathogen, Cryptococcus neoformans. Wild-type males show greater
      resistance than hermaphrodite animals to killing by this pathogen and this
      resistance can be induced in hermaphrodite animals by inappropriate activation of
      the male sex-determination pathway. Resistance is molecularly determined, rather
      than resulting from behavioral changes or reproductive differences, and requires
      the activity of the stress-response transcription factor DAF-16. Finally, we
      demonstrate that resistance to C. neoformans correlates broadly with longevity
      within the Caenorhabditis genus. Our results hint at an overlap between the
      pathways controlling immunity and longevity and raise the possibility that
      differential regulation of these pathways may contribute to sex-dependent and
      species-dependent variation.

PMID- 16582431
TI  - Sex ratio variation in Iberian pigs.
AB  - Within the area of sex allocation, one of the topics that has attracted a lot of
      attention is the sex ratio problem. Fisher (1930) proposed that equal numbers of
      males and females have been promoted by natural selection and it has an adaptive
      significance. But the empirical success of Fisher's theory remains doubtful
      because a sex ratio of 0.50 is also expected from the chromosomal mechanism of
      sex determination. Another way of approaching the subject is to consider that
      Fisher's argument relies on the underlying assumption that offspring inherit
      their parent's tendency in biased sex ratio and therefore that genetic variance
      for this trait exists. Here, we analyzed sex ratio data of 56,807 piglets coming
      from 550 boars and 1893 dams. In addition to classical analysis of heterogeneity
      we performed analyses fitting linear and threshold animal models in a Bayesian
      framework using Gibbs sampling techniques. The marginal posterior mean of
      heritability was 2.63 x 10(-4) under the sire linear model and 9.17 x 10(-4)
      under the sire threshold model. The probability of the hypothesis p(h(2) = 0)
      fitting the last model was 0.996. Also, we did not detect any trend in sex ratio
      related to maternal age. From an evolutionary point of view, the chromosomal sex
      determination acts as a constraint that precludes control of offspring sex ratio
      in vertebrates and it should be included in the general theory of sex allocation.
      From a practical view that means that the sex ratio in domestic species is hardly
      susceptible to modification by artificial selection.

PMID- 16582433
TI  - Linkage disequilibrium between incompatibility locus region genes in the plant
      Arabidopsis lyrata.
AB  - We have studied diversity in Arabidopsis lyrata of sequences orthologous to the
      ARK3 gene of A. thaliana. Our main goal was to test for recombination in the S
      locus region. In A. thaliana, the single-copy ARK3 gene is closely linked to the
      non-functional copies of the self-incompatibility loci, and the ortholog in A.
      lyrata (a self-incompatible species) is in the homologous genome region and is
      known as Aly8. It is thus of interest to test whether Aly8 sequence diversity is
      elevated due to close linkage to the highly polymorphic incompatibility locus, as
      is theoretically predicted. However, Aly8 is not a single-copy gene, and the
      presence of paralogs could also lead to the appearance of elevated diversity. We
      established a typing approach based on different lengths of Aly8 PCR products and
      show that most A. lyrata haplotypes have a single copy, but some have two gene
      copies, both closely linked to the incompatibility locus, one being a pseudogene.
      We determined the phase of multiple haplotypes in families of plants from
      Icelandic and other populations. Different Aly8 sequence types are associated
      with different SRK alleles, while haplotypes with the same SRK sequences tend to
      have the same Aly8 sequence. There is evidence of some exchange of sequences
      between different Aly8 sequences, making it difficult to determine which ones are
      allelic or to estimate the diversity. However, the homogeneity of the Aly8
      sequences of each S-haplotype suggests that recombination between the loci has
      been very infrequent over the evolutionary history of these populations. Overall,
      the results suggest that recombination rarely occurs in the interval between the
      S-loci and Aly8 and that linkage to the S-loci can probably account for the
      observed high Aly8 diversity.

PMID- 16582432
TI  - Construction of a 10,000-marker ultradense genetic recombination map of potato:
      providing a framework for accelerated gene isolation and a genomewide physical
      map.
AB  - An ultradense genetic linkage map with >10,000 AFLP loci was constructed from a
      heterozygous diploid potato population. To our knowledge, this is the densest
      meiotic recombination map ever constructed. A fast marker-ordering algorithm was
      used, based on the minimization of the total number of recombination events
      within a given marker order in combination with genotyping error-detection
      software. This resulted in "skeleton bin maps," which can be viewed as the most
      parsimonious marker order. The unit of distance is not expressed in centimorgans
      but in "bins." A bin is a position on the genetic map with a unique segregation
      pattern that is separated from adjacent bins by a single recombination event.
      Putative centromeres were identified by a strong clustering of markers, probably
      due to cold spots for recombination. Conversely, recombination hot spots resulted
      in large intervals of up to 15 cM without markers. The current level of marker
      saturation suggests that marker density is proportional to physical distance and
      independent of recombination frequency. Most chromatids (92%) recombined once or
      never, suggesting strong chiasma interference. Absolute chiasma interference
      within a chromosome arm could not be demonstrated. Two examples of contig
      construction and map-based cloning have demonstrated that the marker spacing was
      in accordance with the expected physical distance: approximately one marker per
      BAC length. Currently, the markers are used for genetic anchoring of a physical
      map of potato to deliver a sequence-ready minimal tiling path of BAC contigs of
      specific chromosomal regions for the potato genome sequencing consortium
      (http://www.potatogenome.net).

PMID- 16582434
TI  - The requirements for COMPASS and Paf1 in transcriptional silencing and
      methylation of histone H3 in Saccharomyces cerevisiae.
AB  - The Set1-containing complex, COMPASS, methylates histone H3 on lysine 4 (K4) in
      Saccharomyces cerevisiae. Despite the preferential association of K4
      trimethylated H3 with regions of the genome that are transcribed by RNA
      polymerase II, transcriptional silencing is one of the few cases in S. cerevisiae
      where histone-methylation defects have a clear effect on gene expression. To
      better understand the role of COMPASS in transcriptional silencing, we have
      determined which members of COMPASS are required for silencing at the ribosomal
      DNA locus (rDNA), a telomere, and the silent mating loci (HM) using Northern
      analyses. Our findings indicate that most members of COMPASS are required for
      silencing at the rDNA and telomere, while none are required for silencing of
      endogenous genes at the HM loci. To complement gene-expression analysis,
      quantitative Western blot experiments were performed to determine the members of
      COMPASS that are required for methylation of histone H3. While most are required
      for trimethylation, cells lacking certain COMPASS proteins maintain reduced
      levels of K4 mono- and dimethylated H3, suggesting that some COMPASS members have
      redundant function. Finally, we show Paf1 is required for silencing and K4
      methylated H3 at the rDNA, suggesting a possible direct role for K4-methylated H3
      in gene silencing.

PMID- 16582435
TI  - A general population-genetic model for the production by population structure of
      spurious genotype-phenotype associations in discrete, admixed or spatially
      distributed populations.
AB  - In linkage disequilibrium mapping of genetic variants causally associated with
      phenotypes, spurious associations can potentially be generated by any of a
      variety of types of population structure. However, mathematical theory of the
      production of spurious associations has largely been restricted to population
      structure models that involve the sampling of individuals from a collection of
      discrete subpopulations. Here, we introduce a general model of spurious
      association in structured populations, appropriate whether the population
      structure involves discrete groups, admixture among such groups, or continuous
      variation across space. Under the assumptions of the model, we find that a single
      common principle--applicable to both the discrete and admixed settings as well as
      to spatial populations--gives a necessary and sufficient condition for the
      occurrence of spurious associations. Using a mathematical connection between the
      discrete and admixed cases, we show that in admixed populations, spurious
      associations are less severe than in corresponding mixtures of discrete
      subpopulations, especially when the variance of admixture across individuals is
      small. This observation, together with the results of simulations that examine
      the relative influences of various model parameters, has important implications
      for the design and analysis of genetic association studies in structured
      populations.

PMID- 16582429
TI  - Lachesis muta (Viperidae) cDNAs reveal diverging pit viper molecules and
      scaffolds typical of cobra (Elapidae) venoms: implications for snake toxin
      repertoire evolution.
AB  - Efforts to describe toxins from the two major families of venomous snakes
      (Viperidae and Elapidae) usually reveal proteins belonging to few structural
      types, particular of each family. Here we carried on an effort to determine
      uncommon cDNAs that represent possible new toxins from Lachesis muta (Viperidae).
      In addition to nine classes of typical toxins, atypical molecules never observed
      in the hundreds of Viperidae snakes studied so far are highly expressed: a
      diverging C-type lectin that is related to Viperidae toxins but appears to be
      independently originated; an ohanin-like toxin, which would be the third member
      of the most recently described class of Elapidae toxins, related to human
      butyrophilin and B30.2 proteins; and a 3FTx-like toxin, a new member of the
      widely studied three-finger family of proteins, which includes major Elapidae
      neurotoxins and CD59 antigen. The presence of these common and uncommon molecules
      suggests that the repertoire of toxins could be more conserved between families
      than has been considered, and their features indicate a dynamic process of venom
      evolution through molecular mechanisms, such as multiple recruitments of
      important scaffolds and domain exchange between paralogs, always keeping a
      minimalist nature in most toxin structures in opposition to their nontoxin
      counterparts.

PMID- 16582436
TI  - The effects of mismatch repair and RAD1 genes on interchromosomal crossover
      recombination in Saccharomyces cerevisiae.
AB  - We have previously shown that recombination between 400-bp substrates containing
      only 4-bp differences, when present in an inverted repeat orientation, is
      suppressed by >20-fold in wild-type strains of S. cerevisiae. Among the genes
      involved in this suppression were three genes involved in mismatch repair--MSH2,
      MSH3, and MSH6--and one in nucleotide excision repair, RAD1. We now report the
      involvement of these genes in interchromosomal recombination occurring via
      crossovers using these same short substrates. In these experiments, recombination
      was stimulated by a double-strand break generated by the HO endonuclease and can
      occur between completely identical (homologous) substrates or between
      nonidentical (homeologous) substrates. In addition, a unique feature of this
      system is that recombining DNA strands can be given a choice of either type of
      substrate. We find that interchromosomal crossover recombination with these short
      substrates is severely inhibited in the absence of MSH2, MSH3, or RAD1 and is
      relatively insensitive to the presence of mismatches. We propose that crossover
      recombination with these short substrates requires the products of MSH2, MSH3,
      and RAD1 and that these proteins have functions in recombination in addition to
      the removal of terminal nonhomology. We further propose that the observed
      insensitivity to homeology is a result of the difference in recombinational
      mechanism and/or the timing of the observed recombination events. These results
      are in contrast with those obtained using longer substrates and may be
      particularly relevant to recombination events between the abundant short repeated
      sequences that characterize the genomes of higher eukaryotes.

PMID- 16582437
TI  - Consequences of defective tubulin folding on heterodimer levels, mitosis and
      spindle morphology in Saccharomyces cerevisiae.
AB  - In budding yeast, the essential roles of microtubules include segregating
      chromosomes and positioning the nucleus during mitosis. Defects in these
      functions can lead to aneuploidy and cell death. To ensure proper mitotic spindle
      and cytoplasmic microtubule formation, the cell must maintain appropriate
      stoichiometries of alpha- and beta-tubulin, the basic subunits of microtubules.
      The experiments described here investigate the minimal levels of tubulin
      heterodimers needed for mitotic function. We have found a triple-mutant strain,
      pac10Delta plp1Delta yap4Delta, which has only 20% of wild-type tubulin
      heterodimer levels due to synthesis and folding defects. The anaphase spindles in
      these cells are approximately 64% the length of wild-type spindles. The mutant
      cells are viable and accurately segregate chromosomes in mitosis, but they do
      have specific defects in mitosis such as abnormal nuclear positioning. The
      results establish that cells with 20% of wild-type levels of tubulin heterodimers
      can perform essential cellular functions with a short spindle, but require higher
      tubulin heterodimer concentrations to attain normal spindle length and prevent
      mitotic defects.

PMID- 16582438
TI  - Differential roles of transcriptional mediator complex subunits Crsp34/Med27,
      Crsp150/Med14 and Trap100/Med24 during zebrafish retinal development.
AB  - The transcriptional mediator complex has emerged as an important component of
      transcriptional regulation, yet it is largely unknown whether its subunits have
      differential functions in development. We demonstrate that the zebrafish mutation
      m885 disrupts a subunit of the mediator complex, Crsp34/Med27. To explore the
      role of the mediator in the control of retinal differentiation, we employed two
      additional mutations disrupting the mediator subunits Trap100/Med24 and
      Crsp150/Med14. Our analysis shows that loss of Crsp34/Med27 decreases amacrine
      cell number, but increases the number of rod photoreceptor cells. In contrast,
      loss of Trap100/Med24 decreases rod photoreceptor cells. Loss of Crsp150/Med14,
      on the other hand, only slightly reduces dopaminergic amacrine cells, which are
      absent from both crsp34(m885) and trap100(lessen) mutant embryos. Our data
      provide evidence for differential requirements for Crsp34/Med27 in developmental
      processes. In addition, our data point to divergent functions of the mediator
      subunits Crsp34/Med27, Trap100/Med24, and Crsp150/Med14 and, thus, suggest that
      subunit composition of the mediator contributes to the control of differentiation
      in the vertebrate CNS.

PMID- 16582439
TI  - Genetic control of X chromosome inactivation in mice: definition of the Xce
      candidate interval.
AB  - In early mammalian development, one of the two X chromosomes is silenced in each
      female cell as a result of X chromosome inactivation, the mammalian dosage
      compensation mechanism. In the mouse epiblast, the choice of which chromosome is
      inactivated is essentially random, but can be biased by alleles at the X-linked X
      controlling element (Xce). Although this locus was first described nearly four
      decades ago, the identity and precise genomic localization of Xce remains
      elusive. Within the X inactivation center region of the X chromosome, previous
      linkage disequilibrium studies comparing strains of known Xce genotypes have
      suggested that Xce is physically distinct from Xist, although this has not yet
      been established by genetic mapping or progeny testing. In this report, we used
      quantitative trait locus (QTL) mapping strategies to define the minimal Xce
      candidate interval. Subsequent analysis of recombinant chromosomes allowed for
      the establishment of a maximum 1.85-Mb candidate region for the Xce locus.
      Finally, we use QTL approaches in an effort to identify additional modifiers of
      the X chromosome choice, as we have previously demonstrated that choice in Xce
      heterozygous females is significantly influenced by genetic variation present on
      autosomes (Chadwick and Willard 2005). We did not identify any autosomal loci
      with significant associations and thus show conclusively that Xce is the only
      major locus to influence X inactivation patterns in the crosses analyzed. This
      study provides a foundation for future analyses into the genetic control of X
      chromosome inactivation and defines a 1.85-Mb interval encompassing all the major
      elements of the Xce locus.

PMID- 16582440
TI  - Dominant mutants of the Saccharomyces cerevisiae ASF1 histone chaperone bypass
      the need for CAF-1 in transcriptional silencing by altering histone and Sir
      protein recruitment.
AB  - Transcriptional silencing involves the formation of specialized repressive
      chromatin structures. Previous studies have shown that the histone H3-H4
      chaperone known as chromatin assembly factor 1 (CAF-1) contributes to
      transcriptional silencing in yeast, although the molecular basis for this was
      unknown. In this work we have identified mutations in the nonconserved C terminus
      of antisilencing function 1 (Asf1) that result in enhanced silencing of HMR and
      telomere-proximal reporters, overcoming the requirement for CAF-1 in
      transcriptional silencing. We show that CAF-1 mutants have a drastic reduction in
      DNA-bound histone H3 levels, resulting in reduced recruitment of Sir2 and Sir4 to
      the silent loci. C-terminal mutants of another histone H3-H4 chaperone Asf1
      restore the H3 levels and Sir protein recruitment to the silent loci in CAF-1
      mutants, probably as a consequence of the weakened interaction between these Asf1
      mutants and histone H3. As such, these studies have identified the nature of the
      molecular defect in the silent chromatin structure that results from inactivation
      of the histone chaperone CAF-1.

PMID- 16582442
TI  - Characterization and mapping of a shattering mutant in rice that corresponds to a
      block of domestication genes.
AB  - Easy shattering reduces yield due to grain loss during harvest in cereals.
      Shattering is also a hindrance in breeding programs that use wild accessions
      because the shattering habit is often linked to desirable traits. We
      characterized a shattering mutant line of rice, Hsh, which was derived from a
      nonshattering japonica variety, Hwacheong, by N-methyl-N-nitrosourea (MNU)
      treatment. The breaking tensile strength (BTS) of the grain pedicel was measured
      using a digital force gauge to evaluate the degree of shattering of rice
      varieties at 5, 10, 15, 20, 25, 30, 35, and 40 days after heading (DAH). The BTS
      of Hwacheong did not decrease with increasing DAH, maintaining a level of 180-240
      gf, while that of Hsh decreased greatly during 10-20 DAH and finally stabilized
      at 50 gf. Optical microscopy revealed that Hsh had a well-developed abscission
      layer similar to the wild rice Oryza nivara (accession IRGC105706), while
      Hwacheong did not produce an abscission layer, indicating that the shattering of
      Hsh was caused by differentiation of the abscission layer. On the basis of the
      BTS value and morphology of the abscission layer of F(1) plants and segregation
      data in F(2) populations, it was concluded that the easy shattering of Hsh was
      controlled by the single recessive gene sh-h. The gene sh-h was determined to be
      located on rice chromosome 7 by bulked segregant analysis. Using 14 SSR markers
      on rice chromosome 7, the gene sh-h was mapped between the flanking markers
      RM8262 and RM7161 at distances of 1.6 and 2.0 cM, respectively. An SSR marker
      Rc17 cosegregated with the gene sh-h. The locus sh-h for shattering was tightly
      linked to the Rc locus conferring red pericarp, as well as a QTL qSD(s)-7-1 for
      seed dormancy, implying that this region might represent a domestication block in
      the evolutionary pathway of rice.

PMID- 16582441
TI  - Contrasting patterns of introgression at X-linked loci across the hybrid zone
      between subspecies of the European rabbit (Oryctolagus cuniculus).
AB  - Hybrid zones provide an excellent opportunity for studying the consequences of
      genetic changes between closely related taxa. Here we investigate patterns of
      genetic variability and gene flow at four X-linked loci within and between the
      two subspecies of European rabbit (Oryctolagus cuniculus cuniculus and O. c.
      algirus). Two of these genes are located near the centromere and two are located
      near the telomeres. We observed a deep split in the genealogy of each gene with
      the root located along the deepest branch in each case, consistent with the
      evolution of these subspecies in allopatry. The two centromeric loci showed low
      levels of variability, high levels of linkage disequilibrium, and little
      introgression between subspecies. In contrast, the two telomeric loci showed high
      levels of variability, low levels of linkage disequilibrium, and considerable
      introgression between subspecies. These data are consistent with suppression of
      recombination near the centromere of the rabbit X chromosome. These observations
      support a view of speciation where genomic incompatibilities at different loci in
      the genome create localized differences in levels of gene flow between nascent
      species.

PMID- 16582443
TI  - Remarkable site specificity of local transposition into the Hsp70 promoter of
      Drosophila melanogaster.
AB  - Heat-shock genes have numerous features that ought to predispose them to
      insertional mutagenesis via transposition. To elucidate the evolvability of heat
      shock genes via transposition, we have exploited a local transposition technique
      and Drosophila melanogaster strains with EPgy2 insertions near the Hsp70 gene
      cluster at 87A7 to produce numerous novel EPgy2 insertions into these Hsp70
      genes. More than 50% of 45 independent insertions were made into two adjacent
      nucleotides in the proximal promoter at positions -96 and -97, and no insertions
      were into a coding or 3'-flanking sequence. All inserted transposons were in
      inverse orientation to the starting transposon. The frequent insertion into
      nucleotides -96 and -97 is consistent with the DNase hypersensitivity, absence of
      nucleosomes, flanking GAGA-factor-binding sites, and nucleotide sequence of this
      region. These experimental insertions recapitulated many of the phenotypes of
      natural transposition into Hsp70: reduced mRNA expression, less Hsp70 protein,
      and decreased inducible thermotolerance. The results suggest that the distinctive
      features of heat-shock promoters, which underlie the massive and rapid expression
      of heat-shock genes upon heat shock, also are a source of evolutionary variation
      on which natural selection can act.

PMID- 16582444
TI  - Evaluation of DNA pooling for the estimation of microsatellite allele
      frequencies: a case study using striped bass (Morone saxatilis).
AB  - Using striped bass (Morone saxatilis) and six multiplexed microsatellite markers,
      we evaluated procedures for estimating allele frequencies by pooling DNA from
      multiple individuals, a method suggested as cost-effective relative to individual
      genotyping. Using moment-based estimators, we estimated allele frequencies in
      experimental DNA pools and found that the three primary laboratory steps, DNA
      quantitation and pooling, PCR amplification, and electrophoresis, accounted for
      23, 48, and 29%, respectively, of the technical variance of estimates in pools
      containing DNA from 2-24 individuals. Exact allele-frequency estimates could be
      made for pools of sizes 2-8, depending on the locus, by using an integer-valued
      estimator. Larger pools of size 12 and 24 tended to yield biased estimates;
      however, replicates of these estimates detected allele frequency differences
      among pools with different allelic compositions. We also derive an unbiased
      estimator of Hardy-Weinberg disequilibrium coefficients that uses multiple DNA
      pools and analyze the cost-efficiency of DNA pooling. DNA pooling yields the most
      potential cost savings when a large number of loci are employed using a large
      number of individuals, a situation becoming increasingly common as microsatellite
      loci are developed in increasing numbers of taxa.

PMID- 16582445
TI  - Assessing the relative ages of admixture in the bovine hybrid zones of Africa and
      the Near East using X chromosome haplotype mosaicism.
AB  - Historical hybridization events between the two subspecies of cattle, Bos taurus
      and B. indicus, have occurred in several regions of the world, while other
      populations have remained nonadmixed. We typed closely linked X chromosome
      microsatellites in cattle populations with differing histories of admixture from
      Africa, Europe, the Near East, and India. Haplotype breakdown will occur as
      admixed populations age, and longer ancestral haplotypes will remain intact in
      more recently admixed populations compared to older ones. We genotyped male
      animals from these populations, obtaining unambiguous haplotypes, and measured
      levels of linkage disequilibrium (LD) and ancestral mosaicism. Extensive LD,
      likely to be the result of ongoing admixture, was discovered in hybrid cattle
      populations from the perimeter of the tsetse zone in West Africa. A Bayesian
      method to assign microsatellite allele ancestry was used to designate the likely
      origin of each chromosomal segment and assess the relative ages of admixture in
      the populations. A gradient of the age of admixture in the African continent
      emerged, where older admixture has produced more fragmented haplotypes in the
      south, and longer intact haplotypes, indicating more recent hybridization,
      feature in the northwest.

PMID- 16582446
TI  - Retroelement genome painting: cytological visualization of retroelement
      expansions in the genera Zea and Tripsacum.
AB  - Divergence of abundant genomic elements among the Zea and Tripsacum genera was
      examined cytologically and a tool kit established for subsequent studies. The LTR
      regions from the CRM, Huck, Grande, Prem1, Prem2/Ji, Opie, Cinful-1, and Tekay
      retroelement families were used as FISH probes on mitotic chromosome spreads from
      a "trispecies" hybrid containing chromosomes from each of three species: Zea mays
      (2n = 20), Z. diploperennis (2n = 20), and Tripsacum dactyloides (2n = 36).
      Except for Tekay, which painted both Zea and Tripsacum chromosomes with nearly
      equal intensity, the retroelement probes hybridized strongly to the Zea
      chromosomes, allowing them to be distinguished from those of Tripsacum. Huck and
      Grande hybridized more intensely to maize than to Z. diploperennis chromosomes.
      Tripsacum genomic clones containing retroelement sequences were isolated that
      specifically paint Tripsacum chromosomes. The retroelement paints proved
      effective for distinguishing different genomes in interspecific hybrids and
      visualizing alien chromatin from T. dactyloides introgressed into maize lines.
      Other FISH probes (180-bp knob, TR-1, 5S, NOR, Cent4, CentC, rp1, rp3, and alpha
      ZeinA) could be simultaneously visualized with the retroelement probes,
      emphasizing the value of the retroelement probes for cytogenetic studies of Zea
      and Tripsacum.

PMID- 16582447
TI  - A new method of estimating the pollen dispersal curve independently of effective
      density.
AB  - We introduce a novel indirect method of estimating the pollen dispersal curve
      from mother-offspring genotypic data. Unlike an earlier indirect approach
      (TwoGener), this method is based on a normalized measure of correlated paternity
      between female pairs whose expectation does not explicitly depend on the unknown
      effective male population density (d(e)). We investigate the statistical
      properties of the new method, by comparison with those of TwoGener, considering
      the sensitivity to reductions of d(e), relative to census density, resulting from
      unequal male fecundity and asynchronous flowering. Our main results are: (i) it
      is possible to obtain reliable estimates of the average distance of pollen
      dispersal, delta, from indirect methods, even under nonuniform male fecundity and
      variable flowering phenology; (ii) the new method yields more accurate and more
      precise delta-estimates than TwoGener under a wide range of sampling and
      flowering scenarios; and (iii) TwoGener can be used to obtain approximate d(e)
      estimates, if needed for other purposes. Our results also show that accurately
      estimating the shape of the tail of the pollen dispersal function by means of
      indirect methods remains a very difficult challenge.

PMID- 16582448
TI  - Disentangling reasons for low Y chromosome variation in the greater white-toothed
      shrew (Crocidura russula).
AB  - Y chromosome variation is determined by several confounding factors including
      mutation rate, effective population size, demography, and selection.
      Disentangling these factors is essential to better understand the evolutionary
      properties of the Y chromosome. We analyzed genetic variation on the Y
      chromosome, X chromosome, and mtDNA of the greater white-toothed shrew, a species
      with low variance in male reproductive success and limited sex-biased dispersal,
      which enables us to control to some extent for life-history effects. We also
      compared ancestral (Moroccan) to derived (European) populations to investigate
      the role of demographic history in determining Y variation. Recent colonization
      of Europe by a small number of founders (combined with low mutation rates) is
      largely responsible for low diversity observed on the European Y and X
      chromosomes compared to mtDNA. After accounting for mutation rate, copy number,
      and demography, the Y chromosome still displays a deficit in variation relative
      to the X in both populations. This is possibly influenced by directional
      selection, but the slightly higher variance in male reproductive success is also
      likely to play a role, even though the difference is small compared to that in
      highly polygynous species. This study illustrates that demography and life
      history effects should be scrutinized before inferring strong selective pressure
      as a reason for low diversity on the Y chromosome.

PMID- 16582449
TI  - Histone H1 of Saccharomyces cerevisiae inhibits transcriptional silencing.
AB  - Eukaryotic genomes contain euchromatic regions, which are transcriptionally
      active, and heterochromatic regions, which are repressed. These domains are
      separated by "barrier elements": DNA sequences that protect euchromatic regions
      from encroachment by neighboring heterochromatin. To identify proteins that play
      a role in the function of barrier elements we have carried out a screen in S.
      cerevisiae. We recovered the gene HHO1, which encodes the yeast ortholog of
      histone H1, as a high-copy modifier of barrier activity. Histone H1 is a linker
      histone that binds the outside of nucleosomes and modifies chromatin dynamics.
      Here we show that Hho1p reinforces the action of several types of barrier
      elements, and also inhibits silencing on its own.

PMID- 16582451
TI  - Editorial retraction.

PMID- 16582450
TI  - Building of an experimental cline with Arabidopsis thaliana to estimate herbicide
      fitness cost.
AB  - Various management strategies aim at maintaining pesticide resistance frequency
      under a threshold value by taking advantage of the benefit of the fitness penalty
      (the cost) expressed by the resistance allele outside the treated area or during
      the pesticide selection "off years." One method to estimate a fitness cost is to
      analyze the resistance allele frequency along transects across treated and
      untreated areas. On the basis of the shape of the cline, this method gives the
      relative contributions of both gene flow and the fitness difference between
      genotypes in the treated and untreated areas. Taking advantage of the properties
      of such migration-selection balance, an artificial cline was built up to optimize
      the conditions where the fitness cost of two herbicide-resistant mutants
      (acetolactate synthase and auxin-induced target genes) in the model species
      Arabidopsis thaliana could be more accurately measured. The analysis of the
      microevolutionary dynamics in these experimental populations indicated mean
      fitness costs of approximately 15 and 92% for the csr1-1 and axr2-1 resistances,
      respectively. In addition, negative frequency dependence for the fitness cost was
      also detected for the axr2-1 resistance. The advantages and disadvantages of the
      cline approach are discussed in regard to other methods of cost estimation. This
      comparison highlights the powerful ability of an experimental cline to measure
      low fitness costs and detect sensibility to frequency-dependent variations.

PMID- 16582452
TI  - [The care of patients with chronic disease. Do we need to change course?].

PMID- 16582453
TI  - [Can a hospital administration be good if it curtails the influence of physicians
      and surgeons?].

PMID- 16582454
TI  - [The health risk associated with smoking has been seriously underestimated. The
      Reykjavik Study].
AB  - OBJECTIVE: To assess the risk for coronary heart disease, myocardial infarction,
      cancer deaths, and all deaths associated with different smoking categories as
      determined by smoking status at a baseline examination only and at a baseline
      with reexamination 15-19 years later (persistent smokers). MATERIAL AND METHODS:
      The participants were a random sample of 2930 men and 3084 women aged 34-61 years
      (when selected in 1967) invited for various standardized examinations under two
      periods, 1967-1972 and 1979-1991 and followed-up until the end of year 2001. The
      main outcome measures were clinical coronary heart disease, myocardial
      infarction, cancer deaths, and all deaths. Risk was calculated for each smoking
      category as determined by two assessments of smoking habits and also compared
      with the risk as determined by one baseline examination only. RESULTS: Mean
      follow-up for men was 26 years (SD 9 years). For women the mean follow-up was 28
      years (SD 7 years). There were substantial differences in hazard ratios (HR) and
      median lifetime in smoking groups as determined by one or two examinations. In
      men the greatest difference in hazard ratios was for cancer deaths (one
      examination: 2.80, two: 3.83) in women for total deaths (3.02 vs. 3.7). Loss of
      median lifetime was greatest in "heavy" cigarette smoking men (one examination:
      eight years; two examinations: 13 years), in women the corresponding figures were
      nine and 10 years, in "light" cigarette smokers, the figures for men were four
      and nine years, and for women four and six years. CONCLUSIONS: Middle-aged men
      smoking one or more packets of cigarettes per day shorten their life expectancy
      by 13 years and middle-aged women by 10 years. Only one baseline determination of
      smoking status with subsequent follow-up underestimates the health risk
      associated with smoking by 15-40% at least in populations where smoking
      prevalence is declining.

PMID- 16582455
TI  - [Health services for children and the implementation of IMCI in Monkey Bay,
      Malawi].
AB  - OBJECTIVES: Examine primary health care services for ill children in a sub
      Saharan African country, assess the appropriateness of the Integrated Management
      of Childhood Illness (IMCI) in such a setting and evaluate its implementation.
      MATERIAL AND METHODS: The study was carried out in March, 2005 in the Monkey Bay
      area, Malawi, in two state-run health facilities that provide services free of
      charge and in three privately run facilities that charge user fees. Data was
      collected from each facility regarding all out-patient visits but in particular
      of children under five years of age (U5s). Interviews were conducted with health
      workers and drug inventories were carried out in the facilities. RESULTS: Eight
      out of 10 health workers were trained in IMCI. It was 1.22 times more likely (RR,
      95% CI 1.18-1.26) that U5s were brought to a state-run facility than a private
      one. Around 4/5 of all disease classifications during the research period are
      dealt with in the IMCI. About half of U5s were classified with malaria, 28% with
      other respiratory infections, 6% with pneumonia, and 5% with diarrhoea. Most IMCI
      recommended drugs were in stock at the time of inspection but all facilities
      lacked at least one recommended drug. CONCLUSION: Results show that IMCI reaches
      the periphery of the health care system in a low-income country such as Malawi.
      They confirm that IMCI deals with the majority of diseases affecting U5s in such
      a setting. User fees seem to influence health care seeking behaviour. It is
      important to support and strengthen health services for ill children in the area,
      support continuous education of staff and ensure availability of drugs and
      equipment.

PMID- 16582456
TI  - [Reporting of adverse drug reactions in Iceland in 1999 to 2004].
AB  - OBJECTIVES: The reporting of adverse drug reactions (ADRs) has been in effect for
      more than 30 years in Iceland. Very few reports were received until a special
      effort was launched in 1999. METHODS: During the period 1999-2004 only 86 ADRs
      were reported to The Icelandic Medicines Control Agency (IMCA). During this
      period the special effort included the publishing of papers and memos and of
      numerous meetings with health care professionals in order to encourage the
      reporting of ADRs. The effort was initiated with a paper in The Icelandic Medical
      Journal in 1999 where the importance of the reporting of ADRs was explained.
      RESULTS: The reporting of ADRs started slowly with 2 reports in year 1999 and 5
      reports in 2000. The number of reports was then close to 20 per year until 2004
      when it rose to 26. Of the 86 reports received the majority (63%) of cases was
      women and only 38% of the total number of reports was serious ADRs. One patient
      died, eight patients had a live threatening reaction and seven had not recovered
      at the time of reporting. About 60% of the reports came from hospitals and health
      care centers. The most commonly reported class of drugs was those acting on the
      central nervous system with 21 reports. CONCLUSIONS: The number of ADR reports
      has been increasing during the past years and this is probably the result of a
      special effort that has been ongoing since year 1999. The number of reports is
      increasing but is still far behind that of the neighboring countries.

PMID- 16582457
TI  - A stochastic model of Min oscillations in Escherichia coli and Min protein
      segregation during cell division.
AB  - The Min system in Escherichia coli directs division to the centre of the cell
      through pole-to-pole oscillations of the MinCDE proteins. We present a one
      dimensional stochastic model of these oscillations which incorporates membrane
      polymerization of MinD into linear chains. This model reproduces much of the
      observed phenomenology of the Min system, including pole-to-pole oscillations of
      the Min proteins. We then apply this model to investigate the Min system during
      cell division. Oscillations continue initially unaffected by the closing septum,
      before cutting off rapidly. The fractions of Min proteins in the daughter cells
      vary widely, from 50%-50% up to 85%-15% of the total from the parent cell,
      suggesting that there may be another mechanism for regulating these levels in
      vivo.

PMID- 16582459
TI  - Gene copy number and cell cycle arrest.
AB  - The cell cycle is an orderly sequence of events which ultimately lead to the
      division of a single cell into two daughter cells. In the case of DNA damage by
      radiation or chemicals, the damage checkpoints in the G1 and G2 phases of the
      cell cycle are activated. This results in an arrest of the cell cycle so that the
      DNA damage can be repaired. Once this is done, the cell continues with its usual
      cycle of activity. We study a mathematical model of the DNA damage checkpoint in
      the G2 phase which arrests the transition from the G2 to the M (mitotic) phase of
      the cell cycle. The tumor suppressor protein p53 plays a key role in activating
      the pathways leading to cell cycle arrest in mammalian systems. If the DNA damage
      is severe, the p53 proteins activate other pathways which bring about apoptosis,
      i.e., programmed cell death. Loss of the p53 gene results in the proliferation of
      cells containing damaged DNA, i.e., in the growth of tumors which may ultimately
      become cancerous. There is some recent experimental evidence which suggests that
      the mutation of a single copy of the p53 gene (in the normal cell each gene has
      two identical copies) is sufficient to trigger the formation of tumors. We study
      the effect of reducing the gene copy number of the p53 and two other genes on
      cell cycle arrest and obtain results consistent with experimental observations.

PMID- 16582458
TI  - Quantitative modeling and data analysis of SELEX experiments.
AB  - SELEX (systematic evolution of ligands by exponential enrichment) is an
      experimental procedure that allows the extraction, from an initially random pool
      of DNA, of those oligomers with high affinity for a given DNA-binding protein. We
      address what is a suitable experimental and computational procedure to infer
      parameters of transcription factor-DNA interaction from SELEX experiments. To
      answer this, we use a biophysical model of transcription factor-DNA interactions
      to quantitatively model SELEX. We show that a standard procedure is unsuitable
      for obtaining accurate interaction parameters. However, we theoretically show
      that a modified experiment in which chemical potential is fixed through different
      rounds of the experiment allows robust generation of an appropriate dataset.
      Based on our quantitative model, we propose a novel bioinformatic method of data
      analysis for such a modified experiment and apply it to extract the interaction
      parameters for a mammalian transcription factor CTF/NFI. From a practical point
      of view, our method results in a significantly improved false positive/false
      negative trade-off, as compared to both the standard information theory based
      method and a widely used empirically formulated procedure.

PMID- 16582461
TI  - Designed aromatic homo-dipeptides: formation of ordered nanostructures and
      potential nanotechnological applications.
AB  - Molecular self-assembly offers new routes for the fabrication of novel materials
      at the nano-scale. Peptide-based nanostructures represent nano-objects of
      particular interest, as they are biocompatible, can be easily synthesized in
      large amounts, can be decorated with functional elements and can be used in
      various biological and non-biological applications. We had previously revealed
      the formation of highly ordered tubular structures by the diphenylalanine
      peptide, the core recognition motif of Alzheimer's beta-amyloid polypeptide, due
      to specific aromatic interactions. We further confirmed this model and
      demonstrated that a non-charged peptide analogue, Ac-Phe-Phe-NH2, self-assembled
      into similar tubular structures. We later explored other amine and carboxyl
      modified diphenylalanine peptide analogues and revealed that these dipeptides can
      form ordered tubular structures at the nanometric scale. Moreover, a very similar
      peptide, the diphenylglycine, self-assembled into ordered nano-spherical
      assemblies. Here we extend our research and explore the self-assembly of other
      homo-aromatic dipeptides in which their phenyl side-chains are modified with
      halogen atoms (di-para-fluoro-Phe, di-pentafluoro-Phe, di-para-iodo-Phe),
      additional phenyl groups (di-4-phenyl-Phe), or with nitro substitutions (di-para
      nitro-Phe). We also probed the effect of the alteration of the phenyl groups with
      naphtyl groups (di-D-1-Nal and di-D-2-Nal). In all cases, well-ordered
      nanostructures were obtained and studied by scanning electron microscopy,
      transmission electron microscopy and vibrational spectroscopy. Taken together,
      the current work and previous ones define the homo-aromatic dipeptide as a
      central motif for the formation of ordered self-assembled tubular, spherical and
      two-dimensional structures at the nano-scale.

PMID- 16582460
TI  - Helices in peptoids of alpha- and beta-peptides.
AB  - Peptoids of alpha- and beta-peptides (alpha- and beta-peptoids) can be obtained
      by shifting the amino acid side chains from the backbone carbon atoms of the
      monomer constituents to the peptide nitrogen atoms. They are, therefore, N
      substituted poly-glycines and poly-beta-alanines, respectively. Due to the
      substituted nitrogen atoms, the ability for hydrogen bond formation between
      peptide bonds gets lost. It may be very interesting to see whether such non
      natural oligomers could be regarded as foldamers, which fold into definite
      backbone conformers. In this paper, we provide a complete overview on helix
      formation in alpha- and beta-peptoids on the basis of systematic theoretical
      conformational analyses employing the methods of ab initio molecular orbital (MO)
      theory. It can be shown that the alpha- and beta-peptoid structures form helical
      structures with both trans and cis peptide bonds despite the missing hydrogen
      bonds. Obviously, the conformational properties of the backbone are more
      important for folding than the possibility of hydrogen bonding. There are close
      relationships between the helices of alpha-peptoids and poly-glycine and poly
      proline helices of alpha-peptides, whereas the helices of beta-peptoids
      correspond to the well-known helical structures of beta-peptides as, for
      instance, the 3(1)-helix of beta-peptides with 14-membered hydrogen-bonded rings.
      Thus, alpha- and beta-peptoids enrich the field of foldamers and may be used as
      useful tools in peptide and protein design.

PMID- 16582462
TI  - Interaction of a peptide nanotube with a water-membrane interface.
AB  - Inserting peptide nanotubes into lipid bilayers modulates the permeability
      properties of the cell wall, thus conferring potential bacteriocidal capability.
      Interaction of a peptide nanotube formed by eight cyclo[RRKWLWLW] subunits with
      the surface of a hydrated dimyristoylphosphatidylcholine bilayer is investigated
      using molecular dynamics simulations. The present sequence of alternated D-L
      alpha-amino acids has been shown to yield remarkable antibacterial in vitro
      activity, and the chosen topoisomer corresponds to the optimum amphipathy of the
      tubular structure, whereby non-polar and charged side chains are segregated by
      the aqueous interface. The cohesion of the nanotube is ensured by a scaffold of
      intermolecular hydrogen bonds between adjacent cyclic peptides, supplemented by
      favorable like-charged contacts of arginine side chains. It is further reinforced
      by interactions of charged residues with the lipid head groups and of non-polar
      residues with the lipid acyl chains. The simulation reveals a partial breaking of
      the synthetic channel accompanying its early insertion into the lipid bilayer.
      The latter opens new questions about how peptide nanotubes permeate the membrane,
      in particular whether or not (i) self-assembly precedes partitioning and (ii)
      translocation occurs with the complete tubular structure.

PMID- 16582463
TI  - Determining suitable lego-structures to estimate stability of larger peptide
      nanostructures using computational methods.
AB  - Nanofibers, nanofilms and nanotubes constructed of one to four strands of oligo
      alpha- and oligo-beta-peptides were obtained by using carefully selected building
      units. Lego-type approaches based on thermoneutral isodesmic reactions can be
      used to reconstruct the total energies of both linear and tubular periodic
      nanostructures with acceptable accuracy. Total energies of several different
      nanostructures were accurately determined with errors typically falling in the
      subchemical range. Thus, attention will be focused on the description of suitable
      isodesmic reactions that have enabled the determination of the total energy of
      polypeptides and therefore offer a very fast, efficient and accurate method to
      obtain energetic information on large and even very large nanosystems.

PMID- 16582466
TI  - The VA, VCD, Raman and ROA spectra of tri-L-serine in aqueous solution.
AB  - The structures of one conformer of the nonionic neutral and zwitterionic species
      of L-serinyl L-serinyl L-serine (SSS or tri-L-serine), together with its cationic
      and anionic species and the capped N-acetyl tri-L-serine N'-methylamide analog
      were optimized with density functional theory with the Becke 3LYP hybrid exchange
      correlation (XC) functional and the PW91 GGA XC functional and the 6-31G* and aug
      cc-pVDZ basis sets. Subsequently, the vibrational absorption, vibrational
      circular dichroism, Raman and Raman optical activity spectra were simulated in
      order to compare them to experimentally measured spectra. In addition, we compare
      to previously reported studies for both structural determination and spectral
      simulations and measurements. A comparison of the various ways to treat the
      effects of the environment and solvation on both the structure and the spectral
      properties is thoroughly investigated for one conformer, with the goal to
      determine which level of theory is appropriate to use in the systematic search of
      the conformational space. In addition, the effects of the counterion, here Cl-
      anion, are also investigated. Here we present the current state of the art in
      nanobiology, where the latest methods in experimental and theoretical vibrational
      spectroscopy are used to gain useful information about the coupling of the
      nuclear, electronic and magnetic degrees of freedom and structure of tri-L-serine
      and its capped peptide analog with the environment.

PMID- 16582464
TI  - The role of molecular modeling in bionanotechnology.
AB  - Molecular modeling is advocated here as a key methodology for research and
      development in bionanotechnology. Molecular modeling provides nanoscale images at
      atomic and even electronic resolution, predicts the nanoscale interaction of
      unfamiliar combinations of biological and inorganic materials, and evaluates
      strategies for redesigning biopolymers for nanotechnological uses. The
      methodology is illustrated in this paper through reviewing three case studies.
      The first one involves the use of single-walled carbon nanotubes as biomedical
      sensors where a computationally efficient, yet accurate, description of the
      influence of biomolecules on nanotube electronic properties through nanotube
      biomolecule interactions was developed; this development furnishes the ability to
      test nanotube electronic properties in realistic biological environments. The
      second case study involves the use of nanopores manufactured into electronic
      nanodevices based on silicon compounds for single molecule electrical recording,
      in particular, for DNA sequencing. Here, modeling combining classical molecular
      dynamics, material science and device physics, described the interaction of
      biopolymers, e.g., DNA, with silicon nitrate and silicon oxide pores, furnished
      accurate dynamic images of pore translocation processes, and predicted signals.
      The third case study involves the development of nanoscale lipid bilayers for the
      study of embedded membrane proteins and cholesterol. Molecular modeling tested
      scaffold proteins, redesigned apolipoproteins found in mammalian plasma that hold
      the discoidal membranes in the proper shape, and predicted the assembly as well
      as final structure of the nanodiscs. In entirely new technological areas such as
      bionanotechnology, qualitative concepts, pictures and suggestions are sorely
      needed; these three case studies document that molecular modeling can serve a
      critical role in this respect, even though it may still fall short on
      quantitative precision.

PMID- 16582465
TI  - Concepts and schemes for the re-engineering of physical protein modules:
      generating nanodevices via targeted replacements with constrained amino acids.
AB  - Physically building complex multi-molecular structures from naturally occurring
      biological macromolecules has aroused a great deal of interest. Here we focus on
      nanostructures composed of re-engineered, natural 'foldamer' building blocks. Our
      aim is to provide some of the underlying concepts and schemes for crafting
      structures utilizing such conformationally relatively stable molecular
      components. We describe how, via chemical biology strategies, it is further
      possible to chemically manipulate the foldamer building blocks toward specific
      shape-driven structures, which in turn could be used toward potential-designed
      functions. We outline the criteria in choosing candidate foldamers from the vast
      biological repertoire, and how to enhance their stability through selected
      targeted replacements by non-proteinogenic conformationally constrained amino
      acids. These approaches combine bioinformatics, high performance computations and
      mathematics with synthetic organic chemistry. The resulting artificially
      engineered self-organizing molecular scale structures take advantage of nature's
      nanobiology toolkit and at the same time improve on it, since their new targeted
      function differs from that optimized by evolution. The major challenge facing
      nanobiology is to be able to exercise fine control over the performance of these
      target-specific molecular machines.

PMID- 16582467
TI  - From peptide-based material science to protein fibrils: discipline convergence in
      nanobiology.
AB  - This paper illustrates the merits of convergence in nanobiology of two seemingly
      disparate fields, material science and computational biology. Traditionally,
      material science has been a discipline involving design and fabrication of
      synthetic polymers consisting of repeating units. Collaboration with synthetic
      organic chemists allowed design of new polymers, with a range of altered
      conformations. Yet, naturally occurring proteins are also materials. Their varied
      sequences and structures should enrich material science providing more complex
      shapes, scaffolds and chemical properties. For material scientists, the enhanced
      coverage of chemical space obtained by integrating proteins and synthetic organic
      chemistry through the introduction of non-natural residues allows a range of new
      useful potential applications.

PMID- 16582468
TI  - Synchronization of coupled nonidentical genetic oscillators.
AB  - The study of the collective dynamics of synchronization among genetic oscillators
      is essential for the understanding of the rhythmic phenomena of living organisms
      at both molecular and cellular levels. Genetic oscillators are biochemical
      networks, which can generally be modelled as nonlinear dynamic systems. We show
      in this paper that many genetic oscillators can be transformed into Lur'e form by
      exploiting the special structure of biological systems. By using a control theory
      approach, we provide a theoretical method for analysing the synchronization of
      coupled nonidentical genetic oscillators. Sufficient conditions for the
      synchronization as well as the estimation of the bound of the synchronization
      error are also obtained. To demonstrate the effectiveness of our theoretical
      results, a population of genetic oscillators based on the Goodwin model are
      adopted as numerical examples.

PMID- 16582470
TI  - Elastic and damping forces generated by confined arrays of dynamic microtubules.
AB  - In addition to serving as structural elements and as tracks for motor proteins,
      microtubules use chemical energy derived from the hydrolysis of GTP to generate
      forces when growing and shrinking. These forces are used to push or pull on
      organelles such as chromosomes and the mitotic spindle. If an array of
      microtubules grows out from a nucleation site and is confined by the periphery of
      the cell, pushing and pulling forces can give rise to interesting collective
      phenomena. In this paper, I show that pushing forces center the array provided
      that the microtubules are dynamic in the sense that they switch from pushing to
      shrinking after reaching the periphery. Microtubule dynamics of free ends is
      neither necessary nor sufficient for centering. Buckling can augment the
      centering force. For small displacements and velocities, the array can be modeled
      very simply as a damped spring. The dynamic stiffness of the array is orders of
      magnitude smaller than its static stiffness, and the relaxation time is on the
      order of the time that it takes for a microtubule to grow from the center to the
      periphery. Replacement of a dynamic polymer array with an equivalent mechanical
      circuit provides a bridge between molecular and cellular mechanics.

PMID- 16582469
TI  - Finite-particle tracking reveals submicroscopic-size changes of mitochondria
      during transport in mitral cell dendrites.
AB  - The mechanisms of molecular motor regulation during bidirectional organelle
      transport are still uncertain. There is, for instance, the unsettled question of
      whether opposing motor proteins can be engaged in a tug-of-war. Clearly, any non
      synchronous activation of the molecular motors of one cargo can principally lead
      to changes in the cargo's shape and size; the cargo's size and shape parameters
      would certainly be observables of such changes. We therefore set out to measure
      position, shape and size parameters of fluorescent mitochondria (during their
      transport) in dendrites of cultured neurons using a finite-particle tracking
      algorithm. Our data clearly show transport-related submicroscopic-size changes of
      mitochondria. The observed displacements of the mitochondrial front and rear ends
      are consistent with a model in which microtubule plus- and minus-end-directed
      motor proteins or motors of the same type but moving along anti-parallel
      microtubules are often out-of-phase and occasionally engaged in a tug-of-war.
      Mostly the leading and trailing ends of mitochondria undergo similar
      characteristic movements but with a substantial time delay between the
      displacements of both ends, a feature reminiscent of an inchworm-like motility
      mechanism. More generally, we demonstrate that observing the position, shape and
      size of actively transported finite objects such as mitochondria can yield
      information on organelle transport that is generally not accessible by tracking
      the organelles' centroid alone.

PMID- 16582471
TI  - Euler buckling-induced folding and rotation of red blood cells in an optical
      trap.
AB  - We investigate the physics of an optically driven micromotor of biological
      origin. When a single, live red blood cell (RBC) is placed in an optical trap,
      the normal biconcave disc shape of the cell is observed to fold into a rod-like
      shape. If the trapping laser beam is circularly polarized, the folded RBC
      rotates. A model based on geometric considerations, using the concept of buckling
      instabilities, captures the folding phenomenon; the rotation of the cell is
      rationalized using the Poincare sphere. Our model predicts that (i) at a critical
      power of the trapping laser beam the RBC shape undergoes large fluctuations, and
      (ii) the torque that is generated is proportional to the power of the laser beam.
      These predictions are verified experimentally. We suggest a possible mechanism
      for the emergence of birefringent properties in the RBC in the folded state.

PMID- 16582472
TI  - On the distribution of state values of reproducing cells.
AB  - Characterizing a cell state by measuring the degree of gene expression as well as
      its noise has gathered much attention. The distribution of such state values
      (e.g., abundances of some proteins) over cells has been measured, and is not only
      a result of intracellular process, but is also influenced by the growth in cell
      number that depends on the state. By incorporating the growth-death process into
      the standard Fokker-Planck equation, a nonlinear temporal evolution equation of
      distribution is derived and then solved by means of eigenfunction expansions.
      This general formalism is applied to the linear relaxation case. First, when the
      growth rate of a cell increases linearly with the state value x, the shift of the
      average x due to the growth effect is shown to be proportional to the variance of
      x and the relaxation time, similar to the biological fluctuation-response
      relationship. Second, when there is a threshold value of x for growth, the
      existence of a critical growth rate, represented again by the variance and the
      relaxation time, is demonstrated. The relevance of the results to the analysis of
      biological data on the distribution of cell states, as obtained for example by
      flow cytometry, is discussed.

PMID- 16582473
TI  - Nonequilibrium self-assembly of linear fibers: microscopic treatment of growth,
      decay, catastrophe and rescue.
AB  - Many of the large structures of cells are constructed from fibers. These fibers
      self-assemble from individual proteins in a far-from-equilibrium fashion.
      Nonequilibrium self-assembly results in a highly dynamic process at the
      subcellular level that can be regulated and tuned to carry out many of the
      biological functions of the cell: growth, division and locomotion. We construct
      and analyze a nonequilibrium model of the dynamic end of a biological fiber that
      possesses site-resolved resolution. We solve for the steady states of this
      nonequilibrium system using a variational method. The results are compared to
      exact numerical solutions for systems with modest size. Using an effective
      reaction coordinate, we construct an effective potential from the steady-state
      distribution. The stochastic transitions of the system can be analyzed in this
      representation. We then apply this method to model microtubule systems.
      Predictions for macroscopic catastrophe, rescue and dynamic instability in the
      steady states are analyzed. We find that the length of the cap of the microtubule
      is small. The relations between the catastrophe/rescue rate and the growth rate
      are also discussed.

PMID- 16582475
TI  - Structure of NADP-dependent glyceraldehyde-3-phosphate dehydrogenase from
      Synechococcus PCC7942 complexed with NADP.
AB  - The crystal structure of NADP-dependent glyceraldehyde-3-phosphate dehydrogenase
      (NADP-GAPDH) from Synechococcus PCC 7942 (S. 7942) in complex with NADP was
      solved by molecular replacement and refined to an R factor of 19.1% and a free R
      factor of 24.0% at 2.5 A resolution. The overall structure of NADP-GAPDH from S.
      7942 was quite similar to those of other bacterial and eukaryotic GAPDHs. The
      nicotinamide ring of NADP, which is involved in the redox reaction, was oriented
      toward the catalytic site. The 2'-phosphate O atoms of NADP exhibited hydrogen
      bonds to the hydroxyl groups of Ser194 belonging to the S-loop and Thr37. These
      residues are therefore considered to be essential in the discrimination between
      NADP and NAD molecules. The C-terminal region was estimated to have an extremely
      flexible conformation and to play an important role in the formation of the
      supramolecular complex phosphoribulokinase (PRK)-regulatory peptide (CP12)-GAPDH,
      which regulates enzyme activities.

PMID- 16582477
TI  - Structure of the manganese superoxide dismutase from Deinococcus radiodurans in
      two crystal forms.
AB  - The structure of the manganese superoxide dismutase (Mn-SOD; DR1279) from
      Deinococcus radiodurans has been determined in two different crystal forms. Both
      crystal forms are monoclinic with space group P2(1). Form I has unit-cell
      parameters a = 44.28, b = 83.21, c = 59.52 angstroms, beta = 110.18 degrees and
      contains a homodimer in the asymmetric unit, with structure refinement (R =
      16.8%, R(free) = 23.6%) carried out using data to d(min) = 2.2 angstroms. Form II
      has unit-cell parameters a = 43.57, b = 87.10, c = 116.42 angstroms, beta = 92.1
      degrees and an asymmetric unit containing two Mn-SOD homodimers; structure
      refinement was effected to a resolution of 2.0 angstroms (R = 17.2%, R(free) =
      22.3%). The resulting structures are compared with that of Mn-SOD from
      Escherichia coli, with which they are shown to be essentially isostructural.

PMID- 16582476
TI  - Structure of the MecI repressor from Staphylococcus aureus in complex with the
      cognate DNA operator of mec.
AB  - The dimeric repressor MecI regulates the mecA gene that encodes the penicillin
      binding protein PBP-2a in methicillin-resistant Staphylococcus aureus (MRSA).
      MecI is similar to BlaI, the repressor for the blaZ gene of beta-lactamase. MecI
      and BlaI can bind to both operator DNA sequences. The crystal structure of MecI
      in complex with the 32 base-pair cognate DNA of mec was determined to 3.8 A
      resolution. MecI is a homodimer and each monomer consists of a compact N-terminal
      winged-helix domain, which binds to DNA, and a loosely packed C-terminal helical
      domain, which intertwines with its counter-monomer. The crystal contains
      horizontal layers of virtual DNA double helices extending in three directions,
      which are separated by perpendicular DNA segments. Each DNA segment is bound to
      two MecI dimers. Similar to the BlaI-mec complex, but unlike the MecI-bla
      complex, the MecI repressors bind to both sides of the mec DNA dyad that contains
      four conserved sequences of TACA/TGTA. The results confirm the up-and-down
      binding to the mec operator, which may account for cooperative effect of the
      repressor.

PMID- 16582478
TI  - Structure of human ubiquitin-conjugating enzyme E2 G2 (UBE2G2/UBC7).
AB  - The human ubiquitin-conjugating enzyme E2 G2 (UBE2G2/UBC7) is involved in protein
      degradation, including a process known as endoplasmic reticulum-associated
      degradation (ERAD). The crystal structure of human UBE2G2/UBC7 was solved at 2.56
      angstroms resolution. The UBE2G2 structure comprises a single domain consisting
      of an antiparallel beta-sheet with four strands, five alpha-helices and two 3(10)
      helices. Structural comparison of human UBE2G2 with yeast Ubc7 indicated that the
      overall structures are similar except for the long loop region and the C-terminal
      helix. Superimposition of UBE2G2 on UbcH7 in a c-Cbl-UbcH7-ZAP70 ternary complex
      suggested that the two loop regions of UBE2G2 interact with the RING domain in a
      similar way to UbcH7. In addition, the extra loop region of UBE2G2 may interact
      with the RING domain or its neighbouring region and may be involved in the
      binding specificity and stability.

PMID- 16582479
TI  - Structure of SAICAR synthase from Thermotoga maritima at 2.2 angstroms reveals an
      unusual covalent dimer.
AB  - As a part of a structural genomics program, the 2.2 angstroms resolution crystal
      structure of the PurC gene product from Thermotoga maritima has been solved. This
      26.2 kDa protein belongs to the phophoribosylaminoimidazole-succinocarboxamide or
      SAICAR synthase family of enzymes, the members of which are involved in de novo
      purine biosynthesis. SAICAR synthase can be divided into three subdomains: two
      alpha+beta regions exhibiting structural homology with ATP-binding proteins and a
      carboxy-terminal subdomain of two alpha-helices. The asymmetric unit contains two
      copies of the protein which are covalently linked by a disulfide bond between
      Cys126(A) and Cys126(B). This 230-amino-acid protein exhibits high structural
      homology with SAICAR synthase from baker's yeast. The protein structure is
      described and compared with that of the ATP-SAICAR synthase complex from yeast.

PMID- 16582480
TI  - Structure of dimerized radixin FERM domain suggests a novel masking motif in C
      terminal residues 295-304.
AB  - ERM (ezrin/radixin/moesin) proteins bind to the cytoplasmic tail of adhesion
      molecules in the formation of the membrane-associated cytoskeleton. The binding
      site is located in the FERM (4.1 and ERM) domain, a domain that is masked in the
      inactive form. A conventional masking motif, strand 1 (residues 494-500 in
      radixin), has previously been identified in the C-terminal tail domain. Here, the
      crystal structure of dimerized radixin FERM domains (residues 1-310) is presented
      in which the binding site of one molecule is occupied by the C-terminal residues
      (residues 295-304, strand 2) of the other molecule. The residues contain a
      conserved motif that is compatible with that identified in the adhesion
      molecules. The residues might serve as a second masking region in the inactive
      form of ERM proteins.

PMID- 16582481
TI  - Expression, purification, crystallization and preliminary phasing of the
      heteromerization domain of the tRNA-export and aminoacylation cofactor Arc1p from
      yeast.
AB  - Eukaryotic aminoacyl-tRNA synthetases (aaRSs) must be integrated into an
      efficient tRNA-export and shuttling machinery. This is reflected by the presence
      of additional protein-protein interaction domains and a correspondingly higher
      degree of complex formation in eukaryotic aaRSs. However, the structural basis of
      interaction between eukaryotic aaRSs and associated protein cofactors has
      remained elusive. The N-terminal heteromerization domain of the tRNA
      aminoacylation and export cofactor Arc1p has been cloned from yeast, expressed
      and purified. Crystals have been obtained belonging to space group C2, with unit
      cell parameters a = 222.32, b = 89.46, c = 126.79 angstroms, beta = 99.39
      degrees. Calculated Matthews coefficients are compatible with the presence of 10
      25 monomers in the asymmetric unit. A complete multiple-wavelength anomalous
      dispersion data set has been collected from a selenomethionine-substituted
      crystal at 2.8 angstroms resolution. Preliminary phasing reveals the presence of
      20 monomers organized in five tetramers per asymmetric unit.

PMID- 16582482
TI  - Crystallization and preliminary X-ray crystallographic studies of the N-terminal
      domain of FadD28, a fatty-acyl AMP ligase from Mycobacterium tuberculosis.
AB  - FadD28 from Mycobacterium tuberculosis belongs to the fatty-acyl AMP ligase
      (FAAL) family of proteins. It is essential for the biosynthesis of a virulent
      phthiocerol dimycocerosate (PDIM) lipid that is only found in the cell wall of
      pathogenic mycobacteria. The N-terminal domain, comprising of the first 460
      residues, was crystallized by the hanging-drop vapour-diffusion method at 295 K.
      The crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a =
      50.97, b = 60.74, c = 136.54 angstroms. The crystal structure of the N-terminal
      domain of FadD28 at 2.35 angstroms resolution has been solved using the MAD
      method.

PMID- 16582483
TI  - Expression, purification and crystallization of a birnavirus-encoded protease,
      VP4, from blotched snakehead virus (BSNV).
AB  - Blotched snakehead virus (BSNV) is a member of the Birnaviridae family that
      requires a virally encoded protease known as VP4 in order to process its
      polyprotein into viral capsid protein precursors (pVP2 and VP3). VP4 belongs to a
      family of serine proteases that utilize a serine/lysine catalytic dyad mechanism.
      A mutant construct of VP4 with a short C-terminal truncation was overexpressed in
      Escherichia coli and purified to homogeneity for crystallization. Using the
      sitting-drop vapour-diffusion method at room temperature, protein crystals with
      two distinct morphologies were observed. Cubic crystals grown in PEG 2000 MME and
      magnesium acetate at pH 8.5 belong to space group I23, with unit-cell parameters
      a = b = c = 143.8 angstroms. Trigonal crystals grown in ammonium sulfate and
      glycerol at pH 8.5 belong to space group P321/P312, with unit-cell parameters a =
      b = 158.2, c = 126.4 angstroms.

PMID- 16582484
TI  - Crystallization and preliminary X-ray diffraction analysis of prephenate
      dehydratase from Mycobacterium tuberculosis H37Rv.
AB  - Tuberculosis remains the leading cause of mortality arising from a bacterial
      pathogen (Mycobacterium tuberculosis). There is an urgent need for the
      development of new antimycobacterial agents. The aromatic amino-acid pathway is
      essential for the survival of this pathogen and represents a target for structure
      based drug design. Accordingly, the M. tuberculosis prephenate dehydratase has
      been cloned, expressed, purified and crystallized by the hanging-drop vapour
      diffusion method using PEG 400 as a precipitant. The crystal belongs to the
      orthorhombic space group I222 or I2(1)2(1)2(1), with unit-cell parameters a =
      98.26, b = 133.22, c = 225.01 angstroms, and contains four molecules in the
      asymmetric unit. A complete data set was collected to 3.2 angstroms resolution
      using a synchrotron-radiation source.

PMID- 16582485
TI  - Purification, crystallization and preliminary X-ray crystallographic analysis of
      the nucleocapsid protein of Bunyamwera virus.
AB  - Bunyamwera virus (BUNV) is the prototypic member of the Bunyaviridae family of
      segmented negative-sense RNA viruses. The BUNV nucleocapsid protein has been
      cloned and expressed in Escherichia coli. The purified protein has been
      crystallized and a complete data set has been collected to 3.3 angstroms
      resolution at a synchrotron source. Crystals of the nucleocapsid protein belong
      to space group C2, with unit-cell parameters a = 384.7, b = 89.8, c = 89.2
      angstroms, beta = 94.4 degrees . Self-rotation function analysis of the X-ray
      diffraction data has provided insight into the oligomeric state of the protein as
      well as the orientation of the oligomers in the asymmetric unit. The structure
      determination of the protein is ongoing.

PMID- 16582487
TI  - Crystallization and preliminary X-ray analysis of the tRNA thiolation enzyme MnmA
      from Escherichia coli complexed with tRNA(Glu).
AB  - MnmA catalyzes a sulfuration reaction to synthesize 2-thiouridine at the wobble
      positions of tRNA(Glu), tRNA(Gln) and tRNA(Lys) in Escherichia coli. The binary
      complex of MnmA and tRNA(Glu) was crystallized in two different crystal forms:
      forms I and II. Cocrystallization of MnmA-tRNA(Glu) with ATP yielded form III
      crystals. The three crystal forms diffracted to 3.1, 3.4 and 3.4 angstroms
      resolution, respectively, using synchrotron radiation at SPring-8. These crystals
      belong to space groups C2, I2(1)2(1)2(1) and C2, with unit-cell parameters a =
      225.4, b = 175.8, c = 53.0 angstroms, beta = 101.6 degrees, a = 101.5, b = 108.0,
      c = 211.2 A and a = 238.1, b = 102.1, c = 108.2 angstroms, beta = 117.0 degrees,
      respectively. The asymmetric units of these crystals are expected to contain two,
      one and two MnmA-tRNA(Glu) complexes, respectively.

PMID- 16582488
TI  - Crystallization and preliminary X-ray diffraction studies on the human Plk1 Polo
      box domain in complex with an unphosphorylated and a phosphorylated target
      peptide from Cdc25C.
AB  - Polo-like kinase (Plk1) is crucial for cell-cycle progression via mitosis.
      Members of the Polo-like kinase family are characterized by the presence of a C
      terminal domain termed the Polo-box domain (PBD) in addition to the N-terminal
      kinase domain. The PBD of Plk1 was cloned and overexpressed in Escherichia coli.
      Crystallization experiments of the protein in complex with an unphosphorylated
      and a phosphorylated target peptide from Cdc25C yield crystals suitable for X-ray
      diffraction analysis. Crystals of the PBD in complex with the phosphorylated
      peptide belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell
      parameters a = 38.23, b = 67.35, c = 88.25 angstroms, alpha = gamma = beta = 90
      degrees, and contain one molecule per asymmetric unit. Crystals of the PBD in
      complex with the unphosphorylated peptide belong to the monoclinic space group
      P2(1), with unit-cell parameters a = 40.18, b = 49.17, c = 56.23 angstroms, alpha
      = gamma = 90, beta = 109.48 degrees, and contain one molecule per asymmetric
      unit. The crystals diffracted to resolution limits of 2.1 and 2.85 angstroms
      using synchrotron radiation at the European Synchrotron Radiation Facility (ESRF)
      and the Swiss Light Source (SLS), respectively.

PMID- 16582486
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of
      pathogen-inducible oxygenase (PIOX) from Oryza sativa.
AB  - Pathogen-inducible oxygenase (PIOX) is a heme-containing membrane-associated
      protein found in monocotyledon and dicotyledon plants that utilizes molecular
      oxygen to convert polyunsaturated fatty acids into their corresponding 2R
      hydroperoxides. PIOX is a member of a larger family of fatty-acid alpha
      dioxygenases that includes the mammalian cyclooxygenase enzymes cyclooxygenase 1
      and 2 (COX-1 and COX-2). Single crystals of PIOX from rice (Oryza sativa) have
      been grown from MPD using recombinant protein expressed in Escherichia coli and
      subsequently extracted utilizing decyl maltoside as the solubilizing detergent.
      Crystals diffract to 3.0 angstroms resolution using a rotating-anode generator
      and R-AXIS IV detector, and belong to space group P1. Based on the Matthews
      coefficient and self-rotation function analyses, there are presumed to be four
      molecules in the asymmetric unit related by noncrystallographic 222 symmetry.

PMID- 16582490
TI  - Overexpression, purification and preliminary X-ray analysis of pullulanase from
      Bacillus subtilis strain 168.
AB  - The AmyX gene encoding pullulanase from the common spore-forming bacterium
      Bacillus subtilis strain 168 was cloned, overexpressed in Escherichia coli,
      purified and crystallized. The recombinant pullulanase was purified to
      homogeneity using ammonium sulfate precipitation, hydrophobic chromatography and
      anion-exchange chromatography, resulting in a specific activity of 24.10 U per
      milligram of protein. SDS-PAGE analysis showed that the molecular weight of the
      protein is approximately 81.0 kDa, which is similar to the calculated molecular
      weight, 81.1 kDa, from its translated cDNA sequence. The k(cat) and K(m) of the
      purified enzyme with pullulan as substrate were approximately 79 s(-1) and 1.284
      mg ml(-1), respectively. X-ray crystallographic analysis of the pullulanase
      crystal showed that the crystal belongs to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a = 70.568, b = 127.68, c = 189.25
      angstroms. The crystal contains two molecules of pullulanase in the asymmetric
      unit, with a solvent content of 53.15%. The crystal diffracted to 2.1 angstroms
      resolution at a synchrotron and is suitable for structure determination.

PMID- 16582489
TI  - Purification, crystallization and preliminary X-ray diffraction of SecDF, a
      translocon-associated membrane protein, from Thermus thermophilus.
AB  - Thermus thermophilus has a multi-path membrane protein, TSecDF, as a single-chain
      homologue of Escherichia coli SecD and SecF, which form a translocon-associated
      complex required for efficient preprotein translocation and membrane-protein
      integration. Here, the cloning, expression in E. coli, purification and
      crystallization of TSecDF are reported. Overproduced TSecDF was solubilized with
      dodecylmaltoside, chromatographically purified and crystallized by vapour
      diffusion in the presence of polyethylene glycol. The crystals yielded a maximum
      resolution of 4.2 angstroms upon X-ray irradiation, revealing that they belonged
      to space group P4(3)2(1)2. Attempts were made to improve the diffraction quality
      of the crystals by combinations of micro-stirring, laser-light irradiation and
      dehydration, which led to the eventual collection of complete data sets at 3.74
      angstroms resolution and preliminary success in the single-wavelength anomalous
      dispersion analysis. These results provide information that is essential for the
      determination of the three-dimensional structure of this important membrane
      component of the protein-translocation machinery.

PMID- 16582491
TI  - Crystallization and preliminary X-ray characterization of a thermostable low
      molecular-weight 1,4-beta-D-glucan glucohydrolase from an alkalothermophilic
      Thermomonospora sp.
AB  - Cellulases catalyze the hydrolysis of beta-1,4-glycosidic linkages within
      cellulose, the most abundant organic polymer on earth. The cellulase (TSC; EC
      3.2.1.4) from an alkalothermophilic Thermomonospora sp. has a low molecular
      weight of 14.2 kDa. It is optimally active at 323 K and stable over the wide pH
      range of 5-9. Moreover, it has bifunctional activity against cellulose and xylan
      polymers. In this study, TSC was purified from the native source and crystallized
      by the hanging-drop vapour-diffusion method. The crystals belong to the
      orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 49.9, b =
      79.5, c = 99.7 angstroms, and diffract to better than 2.3 angstroms resolution.

PMID- 16582492
TI  - Crystallization, X-ray diffraction analysis and SIRAS/molecular-replacenent
      phasing of three crystal forms of Anabaena sensory rhodopsin transducer.
AB  - Anabaena sensory rhodopsin transducer (ASRT) is a 14.7 kDa soluble signaling
      protein associated with the membrane-embedded light receptor Anabaena sensory
      rhodopsin (ASR) from Anabaena sp., a freshwater cyanobacterium. Crystals of ASRT
      were obtained in three different space groups, P4, C2 and P2(1)2(1)2(1), which
      diffract to 1.8, 2.1 and 2.0 angstroms, respectively. Phases for one of these
      crystal forms (P4) were obtained by SIRAS phasing using an iodide quick-soak
      derivative and a partial model was built. Phases for the remaining crystal forms
      were obtained by molecular replacement using the partial model from the P4
      crystal form.

PMID- 16582493
TI  - Purification, crystallization and preliminary X-ray characterization of the human
      GTP fucose pyrophosphorylase.
AB  - The human nucleotide-sugar metabolizing enzyme GTP fucose pyrophosphorylase
      (GFPP) has been purified to homogeneity by an affinity chromatographic procedure
      that utilizes a novel nucleoside analog. This new purification regime results in
      a protein preparation that produces significantly better crystals than
      traditional purification methods. The purified 66.6 kDa monomeric protein has
      been crystallized via hanging-drop vapor diffusion at 293 K. Crystals of the
      native enzyme diffract to 2.8 angstroms and belong to the orthorhombic space
      group P2(1)2(1)2(1). There is a single GFPP monomer in the asymmetric unit,
      giving a Matthews coefficient of 2.38 angstroms3 Da(-1) and a solvent content of
      48.2%. A complete native data set has been collected as a first step in
      determining the three-dimensional structure of this enzyme.

PMID- 16582494
TI  - Expression, purification, crystallization and preliminary X-ray diffraction of a
      novel Nitrosomonas europaea cytochrome, cytochrome P460.
AB  - Cytochrome P460 from Nitrosomonas europaea, a novel mono-heme protein containing
      an unusual cross-link between a conserved lysine and the porphyrin ring, has been
      recombinantly expressed and purified from Escherichia coli. The protein
      crystallizes readily and diffraction to 1.7 angstroms has been obtained in-house.
      The crystals belong to the trigonal space group P3(1/2)21, with unit-cell
      parameters a = b = 53.3, c = 127.1 angstroms, and contain one monomer in the
      asymmetric unit.

PMID- 16582495
TI  - Crystallization and preliminary X-ray studies of dUTPase from Mason-Pfizer monkey
      retrovirus.
AB  - Deoxyuridine 5'-triphosphate nucleotidohydrolase from Mason-Pfizer monkey
      retrovirus (M-PMV dUTPase) is a betaretroviral member of the dUTPase enzyme
      family. In the mature M-PMV virion, this enzyme is present as the C-terminal
      domain of the fusion protein nucleocapsid-dUTPase. The homotrimeric organization
      characteristic of dUTPases is retained in this bifunctional fusion protein. The
      fusion protein supposedly plays a role in adequate localization of dUTPase
      activity in the vicinity of nucleic acids during reverse transcription and
      integration. Here, the nucleocapsid-free dUTPase (48 426 Da) was cocrystallized
      with a dUTP substrate analogue using the hanging-drop vapour-diffusion method.
      The obtained crystals belong to the primitive hexagonal space group P6(3), with
      unit-cell parameters a = 60.6, b = 60.6, c = 63.6 angstroms, alpha = 90, beta =
      90, gamma = 120 degrees. Native and PtCl4-derivative data sets were collected
      using synchrotron radiation to 1.75 and 2.3 angstroms, respectively. Phasing was
      successfully performed by isomorphous replacement combined with anomalous
      scattering.

PMID- 16582496
TI  - Crystallization and preliminary X-ray analysis of the C-terminal RNase III domain
      of human Dicer.
AB  - Human Dicer protein contains two RNase III domains (RNase IIIa and RNase IIIb)
      which are involved in the production of short interfering RNAs (siRNAs). The C
      terminal RNase III domain (RNase IIIb) of human Dicer was expressed, purified and
      crystallized by the sitting-drop vapour-diffusion method. The crystals belonged
      to space group C222(1), with unit-cell parameters a = 88.6, b = 199.7, c = 119.6
      angstroms, and diffracted X-rays to 2.0 angstroms resolution. The asymmetric unit
      contained three molecules of the RNase IIIb and the solvent content was 67%.

PMID- 16582497
TI  - Expression, purification and crystallization of the SARS-CoV macro domain.
AB  - Macro domains or X domains are found as modules of multidomain proteins, but can
      also constitute a protein on their own. Recently, biochemical and structural
      studies of cellular macro domains have been performed, showing that they are
      active as ADP-ribose-1''-phosphatases. Macro domains are also present in a number
      of positive-stranded RNA viruses, but their precise function in viral replication
      is still unknown. The major human pathogen severe acute respiratory syndrome
      coronavirus (SARS-CoV) encodes 16 non-structural proteins (nsps), one of which
      (nsp3) encompasses a macro domain. The SARS-CoV nsp3 gene region corresponding to
      amino acids 182-355 has been cloned, expressed in Escherichia coli, purified and
      crystallized. The crystals belong to space group P2(1), with unit-cell parameters
      a = 37.5, b = 55.6, c = 108.9 angstroms, beta = 91.4 degrees, and the asymmetric
      unit contains either two or three molecules. Both native and selenomethionine
      labelled crystals diffract to 1.8 angstroms.

PMID- 16582498
TI  - Crystallization and preliminary X-ray diffraction analysis of Nsp15 from SARS
      coronavirus.
AB  - The non-structural protein Nsp15 from the aetiological agent of SARS (severe
      acute respiratory syndrome) has recently been characterized as a uridine-specific
      endoribonuclease. This enzyme plays an essential role in viral replication and
      transcription since a mutation in the related H229E human coronavirus nsp15 gene
      can abolish viral RNA synthesis. SARS full-length Nsp15 (346 amino acids) has
      been cloned and expressed in Escherichia coli with an N-terminal hexahistidine
      tag and has been purified to homogeneity. The protein was subsequently
      crystallized using PEG 8000 or 10 000 as precipitants. Small cubic crystals of
      the apoenzyme were obtained from 100 nl nanodrops. They belong to space group
      P4(1)32 or P4(3)32, with unit-cell parameters a = b = c = 166.8 angstroms.
      Diffraction data were collected to a maximum resolution of 2.7 angstroms.

PMID- 16582499
TI  - Purification, crystallization and preliminary crystallographic analysis of RecA
      superfamily ATPase PH0284 from Pyrococcus horikoshii OT3.
AB  - Circadian (daily) protein clocks are found in cyanobacteria, where a complex of
      the KaiA, KaiB and KaiC proteins generates circadian rhythms. The 28.09 kDa KaiC
      homologue PH0284 protein from Pyrococcus horikoshii OT3 was cloned and expressed
      and the purified protein was crystallized by the oil-microbatch method at 295 K.
      X-ray diffraction data from the crystal were collected to 2.0 angstroms
      resolution using synchrotron radiation at 100 K. The crystal belongs to the
      trigonal space group P3(2)21, with unit-cell parameters a = b = 96.06, c = 298.90
      angstroms. Assuming the presence of one hexamer in the asymmetric unit gives a
      V(M) value of 2.36 angstroms3 Da(-1) and a solvent content of 47.9%. A cocrystal
      with ATP was prepared and a diffraction data set was collected at 2.3 angstroms
      resolution.

PMID- 16582500
TI  - Expression, crystallization and preliminary X-ray crystallographic studies of the
      outer membrane protein OmpW from Escherichia coli.
AB  - OmpW is an eight-stranded 21 kDa molecular-weight beta-barrel protein from the
      outer membrane of Gram-negative bacteria. It is a major antigen in bacterial
      infections and has implications in antibiotic resistance and in the oxidative
      degradation of organic compounds. OmpW from Escherichia coli was cloned and the
      protein was expressed in inclusion bodies. A method for refolding and
      purification was developed which yields properly folded protein according to
      circular-dichroism measurements. The protein has been crystallized and crystals
      were obtained that diffracted to a resolution limit of 3.5 angstroms. The
      crystals belong to space group P422, with unit-cell parameters a = 122.5, c =
      105.7 angstroms. A homology model of OmpW is presented based on known structures
      of eight-stranded beta-barrels, intended for use in molecular-replacement trials.

PMID- 16582501
TI  - Purification, crystallization and preliminary X-ray diffraction studies of N
      acetylglucosamine-phosphate mutase from Candida albicans.
AB  - N-acetylglucosamine-phosphate mutase (AGM1) is an essential enzyme in the
      synthesis of UDP-N-acetylglucosamine (UDP-GlcNAc) in eukaryotes and belongs to
      the alpha-D-phosphohexomutase superfamily. AGM1 from Candida albicans (CaAGM1)
      was purified and crystallized by the sitting-drop vapour-diffusion method. The
      crystals obtained belong to the primitive monoclinic space group P2(1), with unit
      cell parameters a = 60.2, b = 130.2, c = 78.0 angstroms, beta = 106.7 degrees.
      The crystals diffract X-rays to beyond 1.8 angstroms resolution using synchrotron
      radiation.

PMID- 16582503
TI  - [Bone in malignant disorders: introduction].
AB  - Patients harboring cancer and other tumors frequently exhibit such bone morbidity
      as metabolic bone diseases and bone metastases. Cancers produce and secrete
      cytokines and growth factors for their growth and survival. Cytokines are also
      produced by reacting immune systems. Those humoral factors, when produced in a
      sizable quantity, enter into the general circulation and become a causative
      principle for paraneoplastic syndrome. An example is parathyroid hormone-related
      protein (PTHrP) for humoral hypercalcemia of malignancy, and fibroblast growth
      factor 23 (FGF23) for oncogenic osteomalacia. In animal models, PTHrP appear to
      produce cancer-associated cachexia as well. Some particular cancers such as those
      of lung, prostate, breast and thyroid are prone to metastasize into bone
      resulting in metastatic bone disease. Interactions between these cancers and
      inhabitant bone cells and bone matrices constitute a favorable condition where
      particular cancer cells deposit and survive. A variety of principle factors,
      mostly signal materials, were identified that are responsible for these
      interactions and these principle factors can be a target for the development of
      new chemotherapeutic agents.

PMID- 16582504
TI  - [Pathophysiology of osteolytic bone metastasis associated with solid cancers].
AB  - Bone is one of the most preferential metastatic target sites for solid cancers
      such as breast, prostate and lung cancers. Although the precise molecular
      mechanisms underlying this predilection are still unclear, it appears that these
      cancer cells possess the capacity to modulate bone microenvironments to
      facilitate their arrest, survival and proliferation. In particular, production of
      bone-resorbing cytokines by these metastatic cancer cells increases osteoclastic
      bone resorption, which in turn promotes the colonization of these cancer cells in
      bone through releasing bone-stored growth factors into the bone marrow cavity.
      This crosstalk between metastatic cancer cells and bone stimulates the
      development and progression of bone metastases. Disruption of this vicious cycle
      leads us to design effective and specific interventions for osteolytic bone
      metastases of solid cancers.

PMID- 16582505
TI  - [Mechanism of osteoblastic bone metastasis of prostate cancer].
AB  - The high prevalence of osteoblastic bone metastasis in prostate cancer is thought
      to be attributable to the production of osteoblast-stimulating factors by
      prostate cancer cells. Prostate-specific antigen (PSA) expression is arguably the
      most distinctive features of prostate cancer. PSA is a serine protease and an
      important serological marker for prostate cancer. Expression, secretion, and
      activation of transforming growth factor-beta (TGF-beta) is induced by PSA, and
      PSA-induced osteoblastic changes in bone were caused by an autonomous increase in
      mature osteoblasts and by depletion of the osteoclast population. Osteoblastic
      changes result from an imbalance between the rate of bone resorption and
      formation.

PMID- 16582506
TI  - [Bone disease in multiple myeloma and its mechanism].
AB  - Multiple myeloma is characterized by accumulation of monoclonal plasma cells in
      the bone marrow and progression of lytic bone lesions. Myeloma cells enhance bone
      resorption by triggering a coordinated increase in RANK ligand and decrease in
      osteoprotegerin in the bone marrow. Macrophage inflammatory protein (MIP)-1alpha
      and MIP-1beta are secreted by myeloma cells, and play a major role in the
      enhancement of bone resorption by myeloma cells. Furthermore, the growth and
      survival of myeloma cells are enhanced by contact with osteoclasts, suggesting
      the presence of a vicious cycle between bone destruction and myeloma cell
      expansion. In addition, myeloma cells secrete soluble Wnt inhibitors, dickkopf
      (Dkk)-1 and secreted Frizzled-related protein (sFRP)-2, to suppress bone
      formation. Thus, myeloma cells closely interact with bone cells in the bone
      marrow microenvironment to enhance bone resorption and concomitantly suppress
      bone formation, which causes the formation of destructive bone lesions and a
      rapid loss of bone. Disruption of the pathognomonically skewed cellular
      interactions in myeloma bone marrow microenvironment may ameliorate bone
      destruction along with myeloma expansion.

PMID- 16582507
TI  - [Diagnostic imaging of skeletal metastases].
AB  - Metastases to bone (skeletal metastases) are the most frequent malignant bone
      tumor. Skeletal metastases can be classified three types;osteolytic, osteoblastic
      and mixed type. These types depend on the nature of primary cancer. Because
      imaging studies visualize bone defect and bone formation, these abnormalities can
      be seen differently depend on the methods to use. In addition, effective therapy
      to skeletal metastases alters the image. Information of primary cancer and what
      kinds of treatment have been performed are essential to a diagnosis of skeletal
      metastasis.

PMID- 16582508
TI  - [Evaluation of cancer-induced bone diseases by bone metabolic marker].
AB  - Recently, several new bone metabolic markers have been developed and applied for
      diagnosis of bone metastasis. We have investigated the efficacy of several bone
      metabolic markers : serum carboxy-terminal telopeptide of type 1 collagen ( I
      CTP), C-terminal cross-linked telopeptide of type I collagen (CTX) and urinary
      free deoxypyridinoline (fDPD) as bone resorption markers, serum carboxy-terminal
      propeptide of type 1 collagen (P I CP), osteocalcin (OC), and bone alkaline
      phosphatase (BAP) as bone formation markers for diagnosis of bone metastasis. I
      CTP was most useful for diagnosis of bone metastasis in breast cancer patients
      because of no increase in postmenopausal osteoporosis. Combination of resorption
      and formation markers increased sensitivity. In follow-up, bone metabolic markers
      seemed more useful for predicting therapeutic response of bone metastasis than
      tumor markers. Bone metabolic markers were also useful for predicting survival or
      occurrence of skeletal-related events. These findings suggest that bone metabolic
      markers would be useful to detect, to monitor, and to predict prognosis of bone
      metastases.

PMID- 16582509
TI  - [Histopathological observations on osteolytic bone metastasis].
AB  - Three types of bone metastasis can be identified : the osteolytic, osteoblastic
      and the intertrabecular metastasis. Bone resorption is believed to be responsible
      for osteolytic metastasis. The early stage of metastatic lesion showed tumor
      cells loosely intermingled with osteoblasts, fibroblastic stromal cells,
      osteoclasts and endothelial cells. In the metastatic nest, many tartrate
      resistant acid phosphatase (TRAP)-positive osteoclasts accumulated in direct
      contact with alkaline phosphatase (ALP)--or receptor activator of NF-kappaB
      ligand (RANKL)-positive osteoblastic cells, indicating the osteoclastogenesis. On
      the other hand, osteoclasts express CD44 while osteopontin was abundant in the
      stromal tissue of tumor nests. Therefore, mediating its affinity for CD44,
      osteopontin may serve to facilitate osteoclastic migration. We review the
      histopathological microenvironment featuring osteoclastic bone resorption,
      angiogenesis and matrix degradation, which appears to facilitate proliferation of
      tumor cells after the onset of bone metastasis.

PMID- 16582510
TI  - [Quality of life in patients with metastatic spinal tumors].
AB  - The authors investigated the postoperative quality of life in 89 patients with
      metastatic spinal tumors. As the results of our study, it was found that spinal
      surgery could maintain or improve the quality of life, and then most of patients
      with poor quality of life had multiple spine/bone metastasis or brain/spinal cord
      metastasis.

PMID- 16582511
TI  - [Mechanism of cancer-induced bone pain].
AB  - Bone pain is one of the major complications of bone metastases and profoundly
      deteriorates quality of life in cancer patients. It has been suggested that the
      nerve injuries by tumor invasion and the inflammatory factors secreted by cancer
      cells are involved in the pathophysiology of bone pain. Recent studies including
      ours suggest that the activation of acid-sensing receptors by tumor-induced
      acidosis in bone metastases also plays a part in causing bone pain. In this
      review, the current understanding of the mechanisms of cancer-induced bone pain
      is discussed.

PMID- 16582512
TI  - [Angiogenesis and metastasis of carcinoma].
AB  - Metastasis of cancer cells from original tumor region plays a major role for the
      malignancy. Released cancer cells attache on the outer membranes of endothelial
      cells of blood vessel, and can go through the wall and settle down in the tissue.
      Growing tumor needs blood supply for the high energy metabolism, but the hypoxic
      condition inside of tumor activates hypoxia inducible factors (HIFs), which
      transactivates several sets of angiogenic factors such as vascular endothelial
      growth factor (VEGF) and basic fibroblast growth factor (bFGF), and induces
      angiogenesis and promotes tumor growth. Physiological angiogenesis, however, is
      regulated under the balance between angiogenic and anti-angiogenic factors. We
      here focus on the role of angiogenesis in tumor metastasis.

PMID- 16582513
TI  - [Tumor metastasis and MMP inhibitor].
AB  - Matrix metalloproteinase (MMP) plays important roles in tumor invasion and
      metastasis by degrading extracellular matrix components including collagen.
      Clinical trials of MMP inhibitor drugs have been carried out, however, they were
      not always as successful as expected.

PMID- 16582514
TI  - [Monoclonal antibody targeting RANKL as a therapy for cancer-induced bone
      diseases].
AB  - Receptor activator of NF-kappaB ligand (RANKL), its receptor RANK, and
      osteoprotegerin (OPG), the physiological inhibitor of RANKL, were discovered
      using a genomics-based approach. Bone loss is dependent on RANKL, the primary
      mediator of osteoclast formation, function, and survival. The study of the
      RANK/RANKL/OPG axis in animal models has firmly established the central
      importance of this pathway in bone mass regulation and provided the initial
      rationale for the design of a mechanism-based targeted approach to inhibit RANKL
      in pathologic bone loss settings, including cancer-induced bone disease.
      Denosumab (AMG 162), a fully human monoclonal antibody that can bind and inhibit
      human RANKL in a way that mimics the natural bone-protecting actions of OPG, is
      currently in development. A phase 1 clinical trial in patients with multiple
      myeloma or breast carcinoma with bone metastases showed that a single
      subcutaneous injection of denosumab caused rapid and sustained suppression of
      bone turnover markers and was well tolerated. Larger trials are underway to
      investigate the effect of denosumab for the treatment of cancer-induced bone
      disease and other bone loss disorders.

PMID- 16582515
TI  - [Latest pain management for painful bony metastases].
AB  - Pain management for painful bony metastases is the most important problem for
      symptom relief of terminally-ill cancer patients. Pathological fractures often
      decrease the activity of daily life (ADL) of patients, and cause deterioration of
      the quality of life (QOL) and prognosis. Basically pharmacological therapies of
      the World Health Organization (WHO) method are essential for symptom relief from
      cancer pain. This article provides the latest pain managements (palliative
      irradiation, bisphosphonate, orthopedic surgery, percutaneous vertebroplasty and
      radiopharmaceutical therapy) of bony metastases, and mentions the indications and
      the problems of these interventions. In consideration to prognosis, the QOL and
      patient's needs, medical staffs have to perform multidisciplinary approach for
      providing suitable palliative care.

PMID- 16582516
TI  - [Palliative radiotherapy for metastatic bone tumor].
AB  - Bone metastases are one of the most common conditions requiring radiation therapy
      today. Its main aim is relief of bone pain, prevention of pathological bone
      fractures as well as its healing, with anticipated effect upon improving
      mobility, function, and quality of life. For localized bone pain, external beam
      radiation therapy (EBRT) will be successful in reducing pain in some 80% of
      patients. However, optimal fraction dose and total doses of EBRT required for
      pain relief have been unknown. According to the recent reports, carbon ion
      radiotherapy seems to be a safe and effective modality in the management of
      metastatic bone tumor not eligible for conventional EBRT. For scattered painful
      metastases, the systemic administration of radioisotopes is thought to be
      effective.

PMID- 16582517
TI  - [Surgical treatment for metastatic bone tumor].
AB  - Conventionally, palliative surgery has been commonly performed as pain management
      for bone metastasis which is regarded as terminal. Recently, medical treatment in
      this area has made great advances and so life expectancy of patients with cancer
      has been prolonged. The objective of surgical treatments is to maintain
      activities of daily living. Radical resection and reconstruction are used for the
      patients with long life expectancy, though palliative surgery is for the patients
      with short life expectancy.

PMID- 16582518
TI  - [Bisphosphonates for bone metastasis of malignant tumor].
AB  - Bone metastasis of a malignant tumor causes various skeletal related events
      (SREs) and often harms patients' QOL. Bisphosphonates is a standard treatment
      medicine for the patient with bone metastasis of a malignant tumor. It is
      possible that Bisphosphonates improve and also maintain their QOL because it
      restrains manifestation of SREs. Particularly zoledronic acid is recommended for
      bone metastasis of all malignant tumors in a guideline of American Society of
      Clinical Oncology (ASCO). Bisphosphonates should be used positively for profit of
      the patient.

PMID- 16582519
TI  - [Treatment of malignancy-associated hypercalcemia].
AB  - Malignancy-associated hypercalcemia (MAH) is caused by tumor over-production of
      parathyroid hormone-related protein (PTHrP), or by locally enhanced bone
      resorption in metastatic lesions of solid cancers. Medical treatment of MAH
      includes hydration by saline infusion, loop diuretics to promote urinary calcium
      excretion and anti-resorptives such as calcitonin and bisphosphonates.
      Particularly, bisphosphonates are the current mainstay for MAH treatment : they
      not only inhibit osteoclastic bone resorption to ameliorate hypercalcemia but can
      also alleviate bone pain and can even prevent cancer cell expansion in bone
      metastatic lesions.

PMID- 16582520
TI  - [Effect of BMP signaling in cartilage and bone formation].
AB  - To investigate roles of bone morphogenic protein (BMP) signaling in cartilage and
      bone formation, tissue-specific transgenic and conditional knockout mice have
      been generated. BMP ligands, antagonists, receptors, Smads, and Smurfs were
      overexpressed or deleted. Comparison of phenotypes between these mice have
      elucidated general roles of BMP signals as well as individual effect of each
      molecule during endochondral bone formation.

PMID- 16582521
TI  - [Vascular development and cartilage formation].
AB  - During endochondral bone formation, resistance to vascular invasion changes in
      association with differentiation and maturation of chondrocytes. Just prior to
      chondrogenesis, the vasculature regresses and avascular cartilaginous bone
      primodia appear. The anti-angiogenic barrier of cartilage is acquired through
      coordinate interactions of extracellular matrices and angiogenesis inhibitors. In
      the process of vascular invasion into cartilage, angiogenesis stimulators and
      matrix degrading enzymes play important roles. In this review, the association of
      angiogenesis with endochondral bone formation will be discussed.

PMID- 16582522
TI  - [Primary hyperparathyroidism complicated with flail chest due to severe
      osteoporosis].
AB  - We report a 61-year-old woman who was admitted to our hospital in August 2004
      with severe hypercalcemia and osteoporosis. Although she was found to have
      hypercalcemia five years earlier, she has never been treated. The patient was
      transferred to our hospital for further management of a recently-identified left
      neck mass. Serum calcium level was 15.0 mg/dL and intact parathyroid hormone
      (PTH) 3,321 pg/mL. (99m)Tc-methoxyisobutylisonitrile (MIBI) scintigraphy showed
      marked accumulation in the left neck. We diagnosed the tumor as parathyroid gland
      tumor and it was enucleated surgically. Although serum Ca level returned to
      normal after surgery, the patient suffered multiple rib fractures, complicated
      with marked paradoxical breathing. Internal fixation of the thorax was necessary
      due to deterioration of the heart failure. Progression of severe osteoporosis was
      associated with multiple fractures of the ribs and other serious complications
      including congestive heart failure occurred after surgery, reflecting the extreme
      difficulty in treating this patient.

PMID- 16582524
TI  - Conscious sedation--an artist's science! An Indian experience with midazolam.
AB  - The present study was undertaken to evaluate Midazolam as a Paediatric conscious
      sedative agent for a routine Indian dental setup and to compare its efficacy and
      safety when administered by intranasal and intramuscular routes, at a dosage of
      0.2 mg/kg body weight. The present study was accomplished in two phases: Phase 1:
      Preliminary dose finding pilot study on 10 children. Phase 2: Single dose,
      randomized parallel clinical trial on 40 children between the ages of 2 and 5
      years. These children were randomly assigned to two groups consisting of 20
      subjects each. Group M, received Midazolam intramuscularly, while Group N
      received Midazolam intranasally. Both the intranasal and intramuscular groups
      showed highly significant decrease in crying levels, motor movements and sensory
      perception levels, post-sedation (P P < 0.001). Midazolam could be safely and
      successfully employed by intranasal and intramuscular routes for Paediatric
      conscious sedation in a routine dental setup with basic facilities at a dosage of
      0.2 mg/ kg body weight. Whenever the clinical situation warrants a faster action,
      peak and recovery, the intranasal route should be the obvious choice.

PMID- 16582525
TI  - Microleakage of restorative materials: an in vitro study.
AB  - The present study was conducted with the aim of evaluating and comparing the
      microleakage of glass ionomer, composite resin and compomers. Class V cavities
      were made in thirty intact caries free premolars and restored with restorative
      materials to be tested respectively. The teeth were thermocycled and subjected to
      silver nitrate dye penetration. They were subsequently sectioned buccolingually.
      Microleakage was evaluated under a stereomicroscope and data subjected to
      statistical analysis. The study concluded that microleakage was evident in all
      restorative materials, with glass ionomer showing maximum leakage followed by
      composite resin. Compomer demonstrated the best results with minimum leakage.

PMID- 16582526
TI  - Dental caries prevalence among preschool children of Hubli: Dharwad city.
AB  - The prevalence of dental caries and treatment needs in the age group of 3-5 years
      was estimated among 1500 children of Hubli-Dharwad city. The attitude of mothers
      towards their children's oral health and its relation with caries prevalence was
      noted among 200 subjects. The prevalence of dental caries was 54.1%. The attitude
      of mothers towards children's oral health made a statistical difference in the
      mean dmft levels.

PMID- 16582527
TI  - Effects of periodontal treatment phase I on birth term and birth weight.
AB  - Considering the high prevalence of preterm birth (PTB) and low birth weight (LBW)
      and their complications as well as the role played by periodontal disease in
      their incidence and the lack of any report of periodontal therapy on these
      problems in Iran, the goal of the present research was to determine the effects
      of periodontal treatment on PLBW incidence among women with moderate or advanced
      periodontitis who were referred to Javaheri hospital (2004-2005). This clinical
      trial research was conducted on 30 pregnant women age ranging from 18-35 years
      old, with moderate or advanced periodontitis. Fifteen subjects randomly underwent
      the first phase of periodontal treatment including scaling, root planning and the
      use of 0.2% chlorhexidine mouth rinse for one week. None of these steps were
      taken for the controls. After necessary follow ups, the effect of periodontal
      treatment on birth term and birth weight were analyzed statistically. This
      research was conducted on 30 subjects, 15 controls and 15 cases in study group.
      In the control group, the observed rate of PLBW was 26.7% whereas among
      periodontally treated group, phase I, PLBW infant was not observed (P < 0.05).
      Infants birth weight were (3059.3-389.7) gms in study group and (3371-394.2) gms
      in the control group and respectively (P < 0.05). Periodontal therapy, phase I,
      results in a reduction in PLBW incidence rate. Therefore, the application of such
      a simple method among periodontally diseased pregnant women is recommended.

PMID- 16582528
TI  - Study of trace elements in mixed saliva of caries free and caries active
      children.
AB  - The present study was carried out to find out the amount of cariogenic and
      cariostatic trace elements in mixed saliva. It was observed that Cu, Pb, Na
      showed significant variation in case of one surface as compared to caries free
      group. Between the non-caries and multiple caries group Cu, Pb, K showed no
      significant variation Zn showed highly significant variation.

PMID- 16582529
TI  - Long term results of mandibular distraction.
AB  - Mandibular distraction osteogenesis has become a popular surgical modality due to
      its many advantages over conventional orthognathic surgical procedures. However,
      in spite of the technique having been used for over 15 years, no concrete long
      term results are available regarding the stability of results. We discuss the
      various studies which have reported either in favour or against the stablility of
      results after distraction. We report a series of 6 cases (3 unilateral and 3
      bilateral distraction) where distraction was carried out before puberty and
      followed them up to seven years after removal of distractors. This case series
      shows that results achieved by distraction osteogenesis are unstable or best
      unpredictable with respect to producing a permanent size increase in the
      mandible. The role of the distraction osteogenesis in overcoming the
      pterygomassetric sling is questionable. We suggest a multicenter study with
      adequate patient numbers treated with a similar protocol and documented after
      growth cessation to have meaningful conclusions on the debate of distraction
      osteogenesis versus orthognathic surgery.

PMID- 16582530
TI  - Management of nasally erupting deciduous canine in operated cleft lip and
      alveolus patient.
AB  - Nasally erupting tooth is a rare finding seen associated with cleft lip and
      alveolus. It may be diagnosed as a result of symptoms such as difficulty in
      breathing, pain on sneezing or blowing the nose or may remain asymptomatic. A
      case of a 4 year old male child operated for bilateral cleft lip and alveolus
      with unilateral right sided nasally erupting deciduous canine is presented here.

PMID- 16582531
TI  - Taurodontism of deciduous and permanent molars: report of two cases.
AB  - Taurodontism is an aberration of teeth that lacks the constriction at the level
      of the CEJ characterized by elongated pulp chambers and apical displacement of
      bifurcation or trifurcation of the roots, giving it a rectangular shape. Its
      occurrence in permanent teeth is common and is quite rare in deciduous dentition.
      Presented in this article are two cases with taurodontism involving deciduous and
      permanent molars.

PMID- 16582532
TI  - Acrocallosal syndrome.
AB  - Presented here is a case of a 8 year old boy with typical clinical manifestations
      of Acrocallosal syndrome. The characteristic features of this syndrome are
      craniofacial abnormalities, distinctive digital malformation, mental retardation.
      The clinical and major nosologic aspects of this condition are discussed.

PMID- 16582533
TI  - Loss of permanent mandibular lateral incisor and canine tooth buds through
      extraoral sinus: report of a case.
AB  - Extraoral sinus tract may occur as a result of an inflammatory process associated
      with the necrotic pulp. Several non odontogenic disorders may also produce an
      extraoral sinus tract, the differential diagnosis of these clinical findings is
      of prime importance in providing appropriate clinical care. Presented here is a
      case report of 4 year old female child with extraoral sinus tract through which
      the tooth buds of mandibular permanent left lateral incisor and mandibular
      permanent left canine were lost. The extraoral sinus was due to mandibular left
      primary canine with class IX fracture (Ellis and Davey's classification).

PMID- 16582534
TI  - Survey of current practices in fellowship orientation.
AB  - BACKGROUND: The transition from medical resident to subspecialty fellow is a
      critical time period in fellowship training that has not been well described. The
      current practices of fellow orientation in pulmonary and critical care training
      programs are not known. OBJECTIVES: The aim of this study was to describe
      orientation practices for training programs in the United States. METHODS: A 10
      question survey was sent via e-mail to program directors of pulmonary/critical
      care fellowship programs identified on the American Thoracic Society (ATS) web
      page of current programs. RESULTS: Eighty-seven programs responded (61.7%), of
      which 86% had a formal orientation program. The mean time spent in fellow
      orientation was 5-10 h in didactic sessions and 0-5 h in wet labs. The most
      frequent didactic sessions were bronchoscopy in 69 programs (80.2%), pulmonary
      function testing in 63 programs (73.3%) and orientation to hospital services in
      63 programs (73.3%). The most frequent use of wet labs was in bronchoscopy
      training in 60 programs (81.1%) and ventilators in 45 programs (60.8%).
      Simulators were used in 37 programs (43%). The majority reported that these areas
      were covered with on the job training, without a formal designated orientation.
      CONCLUSION: This survey demonstrated that early fellow training differs across
      programs in both time spent and clinical and procedural topics covered. An early,
      standardized approach to clinical and procedural training can assure appropriate
      exposure that cannot be guaranteed by on the job training. To provide
      justification for such an approach, clinical outcomes need to be correlated with
      training methods.

PMID- 16582535
TI  - Evaluating the use of a Streptococcus pneumoniae urinary antigen detection kit
      for the management of community-acquired pneumonia in Japan.
AB  - BACKGROUND: The urinary antigen detection kit for Streptococcus pneumoniae was
      tested. OBJECTIVES: It was our aim to evaluate the usefulness of the
      immunochromatographic membrane test by doing a large prospective study of
      community-acquired pneumonia (CAP) in Japan. METHODS: We prospectively evaluated
      the use of the S. pneumoniae urinary antigen detection kit and analyzed the
      treatment and clinical effect seen in patients with positive test kit results.
      One hundred and fifty-six patients with CAP admitted to our hospital between
      October 2001 and September 2003 were evaluated. RESULTS: In 49% of these CAP
      patients, the causative microorganisms were isolated. S. pneumoniae was suspected
      to be the causative microorganism in 15%, but positive results of the urinary
      antigen detection kit indicated S. pneumoniae to be a probable microorganism in
      28%, even though antibiotics had previously been administered to half of the
      patients. The kit was particularly useful for diagnosing patients with poor
      quality sputum in whom antibiotics treatment nevertheless had to be selected.
      Antibiotics appropriate for S. pneumoniae (mainly penicillin) were given. The
      treatment was found to have excellent clinical results in 89% of the CAP
      patients. CONCLUSIONS: The S. pneumoniae urinary antigen detection kit was
      considered to be useful in selecting treatment since there was a high level of
      clinical effectiveness when the most suitable antibiotics were immediately
      administered to positive patients. The use of the S. pneumoniae urinary antigen
      kit is rapid and simple compared with conventional microbiological procedures.

PMID- 16582536
TI  - A male with pleuritic chest pain, dry cough, progressive dyspnoea, and weight
      loss.

PMID- 16582537
TI  - Cortical excitatory amino acid release and cell function during hypotension in
      near-term born lambs.
AB  - BACKGROUND: Energy failure due to insufficient cerebral O2-supply leads to excess
      accumulation of calcium ions in presynaptic neurons, followed by excess release
      of excitatory amino acids, which are potent neurotoxins, into the synaptic cleft.
      AIM: To investigate whether electrocortical brain activity (ECBA) can provide an
      adequate measure for excitatory amino acid release due to hemorrhagic
      hypotension. METHODS: Ten near-term lambs were delivered at 127 days of gestation
      (term: 147 days). After a stabilization period, hypotension was induced by
      stepwise withdrawal of blood. Cerebral microdialysis was used to measure the
      concentrations of glutamate and aspartate. RESULTS: During hypotension, mean
      arterial blood pressure, cerebral O2-supply and ECBA decreased and the
      extracellular concentration of glutamate increased significantly. ECBA was
      significantly related to glutamate (R2: 0.67, p < 0.001) and aspartate (R2: 0.57,
      p < 0.001) concentrations. CONCLUSION: The extracellular release of glutamate and
      aspartate in the cerebral cortex increases after hemorrhagic hypotension in near
      term born lambs. The extracellular overflow of glutamate and aspartate were
      significantly inversely related to ECBA.

PMID- 16582538
TI  - BAY 41-2272, a direct activator of soluble guanylate cyclase, reduces right
      ventricular hypertrophy and prevents pulmonary vascular remodeling during chronic
      hypoxia in neonatal rats.
AB  - Exposure to hypoxia during the first weeks of life in newborn rats decreases
      vascular growth and alveolarization and causes pulmonary hypertension (PH). BAY
      41-2272 is a novel direct activator of soluble guanylate cyclase independent of
      nitric oxide, effective as an acute pulmonary vasodilator in an animal model of
      persistent pulmonary hypertension of the newborn, but whether prolonged BAY 41
      2272 therapy is effective in the setting of chronic PH is unknown. We hypothesize
      that BAY 41-2272 would prevent PH induced by chronic exposure to neonatal
      hypoxia. At 2 days of age, newborn rats were randomly exposed to hypoxia (FiO2,
      0.12) or room air, and received daily intramuscular treatment with BAY 41-2272 (1
      mg/kg) or saline. After 2 weeks, rats were killed for assessment of right
      ventricular hypertrophy (RVH), wall thickness of small pulmonary arteries,
      vessels density, radial alveolar counts and mean linear intercepts. In comparison
      with control, hypoxia increased RVH and artery wall thickness, reduced vessels
      density, decreased radial alveolar counts and increased mean linear intercepts.
      In comparison with hypoxic controls, prolonged BAY 41-2272 treatment during
      chronic hypoxia reduced RVH (0.67 +/- 0.03 vs. 0.52 +/- 0.05; p < 0.05), and
      attenuated artery wall thickness (48.2 +/- 2.8% vs. 35.7 +/- 4.1 microm; p <
      0.01). However, BAY 41-2272 did not change vessels density, radial alveolar
      counts or mean linear intercepts. We conclude that BAY 41-2272 prevents the
      vascular structural effects of PH and reduces RVH but does not protect from
      hypoxia-induced inhibition of alveolarization and vessel growth. We speculate
      that BAY 41-2272 may provide a new therapy for chronic PH.

PMID- 16582539
TI  - The timing of neonatal brain damage.
AB  - Although neonatal morbidity and mortality are less than in the past, the risk of
      pre-natal and neonatal brain damage has not been eliminated. In order to optimize
      pre-natal, perinatal and neonatal care, it is necessary to detect factors
      responsible for brain damage and obtain information about their timing. Knowledge
      of the timing of asphyxia, infections and circulatory abnormalities would enable
      obstetricians and neonatologists to improve prevention in pre-term and full-term
      neonates. Cardiotocography has been criticized as being too indirect a sign of
      fetal condition and as having various technical pitfalls, though its reliability
      seems to be improved by association with pulse oximetry, fetal blood pH and
      electrocardiography. Neuroimaging is particularly useful to determine the timing
      of hypoxic-ischemic brain damage. Cranial ultrasound has been used to determine
      the type and evolution of brain damage. Magnetic resonance has also been used to
      detect antenatal, perinatal and neonatal abnormalities and timing on the basis of
      standardized assessment of brain maturation. Advances in the interpretation of
      neonatal electroencephalograms have also made this technique useful for
      determining the timing of brain lesions. Nucleated red blood cell count in cord
      blood has been recognized as an important indication of the timing of pre-natal
      hypoxia, and even abnormal lymphocyte and thrombocyte counts may be used to
      establish pre-natal asphyxia. Cord blood pH and base excess are well-known
      markers of fetal hypoxia, but are best combined with heart rate and blood
      pressure. Other markers of fetal and neonatal hypoxia useful for determining the
      timing of brain damage are assays of lactate and markers of oxidative stress in
      cord blood and neonatal blood. Cytokines in blood and amniotic fluid may indicate
      chorioamnionitis or post-natal infections. The determination of activin and
      protein S100 has also been proposed. Obstetricians and neonatologists can
      therefore now rely on various methods for monitoring the risk of brain damage in
      the antenatal and post-natal periods.

PMID- 16582541
TI  - Rac2 as a potential cause of impaired neonatal neutrophil chemotaxis. Commentary
      to Meade et al.: Rac2 concentrations in umbilical cord neutrophils (biol neonate
      2006;90:156-159).

PMID- 16582540
TI  - Rac2 concentrations in umbilical cord neutrophils.
AB  - BACKGROUND: Human newborn infants display a variety of immunodeficiencies of
      immaturity, including diminished neutrophil adhesion, chemotaxis, and migration.
      Rac2, a guanosine triphosphate-binding protein, is an essential regulator of
      human neutrophil migration and chemotaxis. Since human subjects and mice
      deficient in Rac2 display deficiencies in neutrophil functions similar to newborn
      infants, we postulated that newborn neutrophils may be deficient in Rac2.
      OBJECTIVES: The aim of the study was to measure Rac1 and Rac2 concentrations in
      neutrophils from umbilical cord blood. METHODS: Neutrophils from cord and adult
      blood were isolated, total cell lysates extracted, and Rac protein concentrations
      determined using Western blot analysis. RESULTS: Rac2 concentrations were
      significantly lower in the neutrophil protein lysates isolated from cord blood
      compared to adult blood despite similar levels of Rac1. CONCLUSIONS: Diminished
      Rac2 expression in cord blood neutrophils may contribute to the defects observed
      in cord blood neutrophil function.

PMID- 16582542
TI  - Nanobacteria, HIV and magic bullets--update of perspectives 2005.
AB  - In 1997 a Finnish group speculated on the presence of nanobacteria in vaccines.
      In 2001, a report on the identification of nanobacteria in a number of vaccines
      attracted much attention. Experiments indicated that viable nanobacteria are
      excreted via urine. Their extreme survivability suggests that prior to discussing
      any possible contamination of vaccines, sources and routes of natural infection
      need to be examined. In view of 30,000,000 HIV infections in sub-Saharan Africa,
      the recently reported occurrence of nanobacteria in HIV-infected patients
      deserves concern. Clearly, it could indicate the origin of a giant reservoir and
      dissemination cycle. Here we discuss novel therapeutic strategies to prevent or
      reduce nanobacterial infection. In regard of the rapid progress in this field, we
      start with a brief introductory summary, and analyze possible implications.

PMID- 16582543
TI  - ET-1 Lys198Asn and ET(A) receptor H323H polymorphisms in heart failure. A case
      control study.
AB  - BACKGROUND: The endothelin (ET) system plays a central role in the control of
      myocardial function and its pathophysiology. The aim of the present study was to
      explore whether genetic variations of ET-1 (G/T substitution that predicts an
      Lys/Asn change at codon 198) and its receptor ET(A) (T/C in exon 6, H323H) could
      predispose carriers to heart failure (HF). METHODS: Genotyping at these two loci
      was done in 122 patients with HF [echocardiographic left ventricular ejection
      fraction (LVEF) < or =40%] and 216 age-matched subjects without HF. Causes of HF
      included ischemic (n = 96) and idiopathic cardiomyopathies (n = 26). RESULTS: The
      ET-1 Lys198Asn was significantly associated with the occurrence of HF (p =
      0.005). The risk of HF was independently increased among Asn/Asn in comparison to
      Lys carriers (OR = 3.2, p = 0.03). Moreover, homozygous carriers of both ET-1 and
      ET(A) variants showed a marked increase in the risk of HF (adjusted OR = 8.6, p =
      0.005), displayed significantly lower LVEF (p = 0.002) and higher left
      ventricular end-diastolic (p = 0.03) and end-systolic diameters (p = 0.04; for
      Asn/Asn and TT vs. Lys and C carriers of the ET-1 and ET(A )polymorphisms,
      respectively). Furthermore, the extent of coronary artery disease (r = -0.62, p <
      0.0001) and the Asn/Asn and TT double genotype (r = -0.30, p = 0.0001) were the
      only significant and independent predictors of LVEF by multivariate analysis.
      CONCLUSIONS: The ET-1 Lys198Asn and ET(A) receptor H323H polymorphisms seem to
      act synergistically to increase the risk of HF.

PMID- 16582544
TI  - Medical and ventilatory treatment of acute heart failure: new insights.
AB  - BACKGROUND: The traditional medical treatment of acute heart failure (AHF) has
      remained unchanged for many years. It has been based on oxygen supplementation
      and mechanical ventilatory support as well as the administration of morphine,
      diuretics, nitrates and inotropic agents. In 2005 the European Society of
      Cardiology (ESC) published new guidelines on the diagnosis and treatment of AHF.
      Also, new therapies have been introduced recently, giving rise to changes in
      therapeutic concepts. MATERIAL/METHOD: Based on these new guidelines and recent
      studies selected from the literature we here describe the new ESC classification
      of AHF including its epidemiology and pathophysiology. We further present a state
      of-the-art status of the choices of medical treatment for patients with acute
      decompensated heart failure and pulmonary edema. RESULTS: Mechanical ventilatory
      support reduces the number of patients who require endotracheal intubation.
      Nitrates in dosages higher than employed today appear to be beneficiary to
      patients with pulmonary congestion, probably because of the pronounced afterload
      reducing effect. Nesiritide, a synthetic brain natriuretic peptide, has shown
      better hemodynamic effects than common nitrate dosages in patients with
      congestive heart failure. Tezosentan, an endothelin antagonist, was tested in the
      biggest AHF trial ever, which, however, was terminated prematurely because it was
      futile to proceed given the endpoints dyspnea and death. The beta1-adrenergic
      drug dobutamine and the phosphodiestherase inhibitor milrinone are associated
      with increased mortality in patients with pronounced chronic and acute congestive
      heart failure. Levosimendan, a new inotropic drug, has shown lower mortality
      compared to dobutamine in patients with acute congestive heart failure.
      CONCLUSION: New concepts have finally emerged, including the application of old
      drugs such as nitrates in new (i.e., higher) dosages, as well as the novel
      compound levosimendan, recommended for patients with AHF and hypoperfused organs.
      The new ESC classification of AHF provides a valuable and long-awaited guideline
      to diagnose and treat this severe condition.

PMID- 16582545
TI  - Magnesium absorption from mineral waters of different magnesium content in
      healthy subjects.
AB  - OBJECTIVE: To assess the absorption of magnesium (Mg) from mineral waters of
      different Mg content in comparison to low mineralized water and a Mg capsule.
      MATERIALS AND METHODS:  DESIGN: Randomized, controlled, double- blind trial in a
      crossover design with an additional control with a Mg capsule. SETTING: Institute
      of Balneology and Medical Climatology, Medical School of Hanover, Germany.
      SUBJECTS: 22 healthy male volunteers aged between 23-46 years. INTERVENTION:
      After a standardized breakfast, each participant received, in Latin square order,
      500 ml of either of two Mg-rich mineral waters (281 or 120 mg/l). As a control
      condition, a mineral water of low Mg content (8 mg/l) was used. A Mg capsule
      (Magnesium-Diasporal 150, Protina, Ismaning, Germany) was used for further
      comparisons. RESULTS: Changes in serum Mg levels in the first 4 hours after
      intake differed significantly between the groups (p = 0.030; ANOVA). Mean values
      differed between the Mg-rich mineral water conditions and the control conditions
      though did not reach statistical significance (p = 0.055), however, mean values
      did not differ between the test waters and the capsule (p = 0.338). CONCLUSION:
      Magnesium from mineral waters can easily be absorbed and its absorption rate is
      similar to that from a pharmaceutical Mg preparation.

PMID- 16582546
TI  - The role of trace elements in homeopathic preparations and the influence of
      container material, storage duration, and potentisation.
AB  - OBJECTIVE: To investigate trace elements in liquid homeopathic preparations and
      the influence of container material, storage duration, and potentisation.
      MATERIALS AND METHODS: Using inductively coupled plasma-mass spectroscopy (ICP
      MS), we investigated (a) aqua bidestillata (ABD) stored for 12 h in either brown
      glass or high density polyethylene (HDPE) bottles; (b) ABD stored for 2 h in
      HDPE, the same additionally filled in brown glass bottle, and ABD potentised in
      brown glass up to C30; (c) -- at 3 different sample ages and with statistical
      analysis -- ABD C30 (brown glass), AgNO3 C30 (brown glass), and controls
      (unsuccussed, brown glass and HDPE). RESULTS: Contamination of the initial ABD
      increased and element concentrations changed far more when stored in brown glass
      bottles than in HDPE. Effects were strongest during initial storage time and
      during the first potentisation step from mother tincture to C1; subsequent
      potentising steps produced no relevant changes. Potencies of AgNO3 and potencies
      of water contained similar contamination. CONCLUSIONS: Potentising accelerates
      material exchange between container and solvent, mostly during succussion.
      Research on potentised preparations should use potentised controls with equal
      preparation and storage time. If physical and biological effects of potencies
      exist, contaminants might be one factor for their generation.

PMID- 16582547
TI  - Effects of mistletoe extract on murine thymocytes in vivo and on glucocorticoid
      induced cell count reduction.
AB  - BACKGROUND: Mistletoe extracts are widely used in cancer patients due to their
      cytostatic and immunomodulatory effects. Essential components include mistletoe
      lectins which act as biomodulators with proinflammatory and apoptosisinducing
      effects. This study investigates the acute and longterm effects of standardized
      mistletoe extract (Iscador(R) M spec 5 mg) on thymocyte subpopulations and
      peripheral T-cells using a murine (Balb/c) model. MATERIALS AND METHODS: Using
      cell surface CD4/CD8 staining and flow cytometry, we followed the changes in CD4
      CD8- double-negative (DN), CD4(+)CD8(+) double-positive (DP) and CD4(+) or CD8(+)
      single-positive (SP) T-cells 24 h after single or repeated injections of 3
      different dilutions (1:12, 1:60, 1:300) corresponding to 2.1, 0.42 and 0.08 mg/kg
      of Iscador. Thymocyte apoptosis was detected by flow cytometry using Annexin V
      and propidium iodide. RESULTS: 24 h after a single injection of the 2 lower
      doses, the number of DN thymocytes increased significantly with an enhanced ratio
      of apoptotic cells. Following administration of the lowest dose, in peripheral
      blood the CD4(+)/CD8(+) ratio was elevated. In the long-term trial, Balb/c mice
      were treated twice a week with 3 different doses of Iscador +/- 20 mg/kg of
      dexamethasone (DX), resulting in significantly enhanced DN thymocytes and
      elevated levels of apoptotic cells after treatment with the 2 lower doses.
      Iscador also inhibited the DX-induced reduction in the thymic DN cell count, as
      well as the DX-induced decrease in the CD4(+)/CD8(+) ratio and CD4(+) in the
      peripheral blood. CONCLUSION: Our results suggest that standardized mistletoe
      extract modulates proliferation and apoptosis of thymocytes in a dose-dependent
      manner and may act lymphoprotective during DX treatment.

PMID- 16582550
TI  - Status of complementary and alternative medicine in European medical schools.
AB  - BACKGROUND: The aim of this study was to investigate whether Complementary and
      Alternative Medicine (CAM) education is part of the regular medical curriculum in
      European universities and whether it correlates with the public demand for CAM
      methods. MATERIALS AND METHODS: Using the World Directory of Medical Schools, 265
      medical faculties in EU countries were contacted via e-mail or regular post and
      asked to fill out a questionnaire of 7 questions concerning CAM education in
      their establishments. RESULTS: Only 40% of the responding universities were
      offering some form of CAM training. We could not show any correlation between the
      public demand for CAM methods and the availability of CAM training in medical
      universities. CONCLUSIONS: The growing popularity of CAM makes it very important
      for physicians to gain information on these methods and techniques, thus better
      incorporation of CAM education into the regular medical curriculum is needed in
      all European medical faculties.

PMID- 16582549
TI  - Randomized double-blind pilot study on psychological effects of a treatment with
      'instrumental biocommunication'.
AB  - BACKGROUND AND OBJECTIVE: Computerized systems using instrumental
      biocommunication for treatment claim beneficial health effects. We set out a
      pilot study to test whether individuals treated with a program called QUANTEC
      report improvements in well-being, health, and fulfillment of prerecorded wishes.
      MATERIALS AND METHODS: 34 volunteers from the University Hospital Freiburg
      participated in the study. Before treatment, baseline measures were taken (self
      report on wishes, well-being, and health). Participants were then randomly and
      blindly allocated to two groups. In the first treatment phase of 3 months
      duration, only half of the participants were treated (group 1). Upon the end of
      the first treatment phase, post-treatment measures were taken. Participants were
      then unblinded as to group allocation and group 2 was treated. Finally, the
      second post-treatment measures were taken. RESULTS: Data exploration revealed
      that individuals' need for health improvement and blinding may be important
      psychological prerequisites for a treatment with instrumental biocommunication to
      be beneficial. CONCLUSIONS: Treatments with QUANTEC may be accompanied by
      beneficial health effects. The latter do not necessarily bear on postulated
      causative mechanisms of treatments with instrumental biocommunication but might
      instead be purely psychological in nature. However, there are a number of
      limitations as to the quality and quantity of such effects which calls for
      further investigation.

PMID- 16582552
TI  - [Professed "entanglement" complementary therapies?].

PMID- 16582548
TI  - [Placebo-controlled study of the effects of a standardized MORA bioresonance
      therapy on functional gastrointestinal complaints].
AB  - BACKGROUND AND OBJECTIVE: Many practitioners of natural medicine as well as a non
      controlled study have reported about positive effects of MORA bioresonance
      therapy on psychosomatic diseases. The present placebo controlled study aimed to
      test the effects of MORA bioresonance therapy on non-organic gastro-intestinal
      complaints. PATIENTS AND METHODS: A randomized, placebo controlled study was
      carried out on 20 participants (10 in the placebo group, 10 in the verum group).
      The main outcome parameters were the patients' and the physician's estimation of
      the intensity and frequency of gastro-intestinal complaints as well as the
      examination results recorded by the physician: stomach pain by palpation,
      meteorism by percussion and intestinal noise by auscultation, assessed pre and
      post treatment. Secondary outcome parameters were the electric resistance between
      hands and feet, data from feces, urine and blood, and the subjective general
      condition of body, mind and soul. RESULTS: According to the participants' and the
      physician's estimation the intensity and frequency of the gastro
      intestinalcomplaints were markedly and significantly reduced in theverum group (p
      < 0.01). This was also true for stomach pain(p < 0.01) and meteorism (p < 0.05),
      but not for intestinal noise (p > 0.05). The main outcome parameters in the
      placebo group changed only slightly (p > 0.05). CONCLUSION: TheMORA bioresonance
      therapy can markedly improve non-organic gastro-intestinal complaints.

PMID- 16582551
TI  - [Bone metastases in breast carcinoma].
AB  - The case of a 66-year-old patient with multiple osteolytic bone metastases caused
      by breast cancer is presented. The patient refused conventional pain therapy
      although she suffered from severe pain. A complementary therapy with homoeopathic
      high potencies, devil's-claw extract, enzymes, alendronate and orthomolecular
      substitution as well as physiotherapy resulted in effective pain relief over a
      period of 1 year. The case is discussed.

PMID- 16582553
TI  - [Tibetan remedies in chronic disease].

PMID- 16582554
TI  - The contribution of the Tibetan Medical System to global health.

PMID- 16582556
TI  - [Tibetan medicine in Europe: historical, practical and regulatory aspects].
AB  - Being one of the great medicine systems of the world, Tibetan Medicine developed
      in the 8th century AD and spread throughout central Asia over the intervening
      centuries. The first European contact with Tibetan remedies started around 1850
      in Russia. By and by, they made their way as far a Switzerland where, in the
      meantime, they have been produced for more than 30 years and licensed by the
      health authorities. During the last years, comprehensive clinical and
      experimental research material has been generated on several formulas, especially
      on Padma 28 and Padma Lax. At the same time, a genuine European pool of
      experience was gained. Tibetan remedies are multicomponent mixtures. Special
      requirements on quality assessment, efficacy and safety arise on the path to a
      modern Tibetan multicompound. The production of such elaborately formulated com
      positions has to take into account modern demands of GMPas well as traditional
      sources. In recent years, a rising popularity of Asian medicine can be observed.
      This need of patients, physicians and therapists also demands answers from the
      regulatory part. Aspects such as the justification of the composition (rationale
      of combination) and certain quality standards have to be newly defined by the
      authorities in this context. Only with adapted regulatory frameworks Tibetan
      medicines can find their place in Europe and, together with other medical
      traditions and biomedical research, integratively enrich the arsenal of
      intervention and prevention of Western industrial societies.

PMID- 16582557
TI  - [Anti-inflammatory potential of Padma 28--review of experimental data on the
      antiatherogenic activity and discussion of the multi-component principle].
AB  - BACKGROUND: The Tibetan remedy Padma 28 has been used in Europe for decades and
      has proved to be effective in inflammatory and atherosclerotic conditions. Beyond
      clinical trials, a large number of in vitro and ex vivo studies report various
      properties and biochemical activities of this complex herbal multicompound.
      OBJECTIVE: To give an overview of the complex efficacy profile of Padma 28, to
      review available data, to relate findings to the development of atherosclerosis
      and thus to discuss the antiatherogenic potential of Padma 28. METHODS: Published
      non-clinical original papers on Padma 28 were collected and classified according
      to the studied mechanisms of action. Results were correlated to the briefly
      described sequences of atherogenesis and various mechanisms of action were
      elaborated, laying particular emphasis on more recent articles. RESULTS: The
      complex activity profile of Padma 28 spans mainly direct and indirect anti
      inflammatory proper-ties as well as further categories of biochemical actions.
      These can be related to the complex processes of atherogenesis. CONCLUSIONS: The
      described mechanisms support the therapeutic field of application of Padma 28,
      i.e. peripheral circulatory disorders as well as chronic inflammatory disorders.
      Moreover, the numerous effects as well as the diversity of sites of action allow
      to draw first conclusions on the conceptual design of this multicomponent
      formula.

PMID- 16582558
TI  - Anti-inflammatory mechanisms of the Tibetan herbal preparation Padma 28 in the
      vessel wall.
AB  - BACKGROUND: The Tibetan herbal preparation Padma 28 has been shown to act as an
      anti-atherosclerotic agent in advanced peripheral arterial occlusive disease. We
      tested the effect of aqueous Padma 28 extracts on both the Creactive protein
      (CRP) induced expression of the pro-inflammatory cell adhesion molecule E
      selectin and the anti-atherosclerotic protective enzyme heme oxygenase- 1 (HO-1)
      in human aortic endothelial cells. METHODS AND RESULTS: According to FACS
      analysis, quantitative RT-PCR and Western blot, CRP-induced E-selectin expression
      was completely prevented by aqueous Padma 28 extracts. Additionally, Padma 28
      mediated an up to 60-fold upregulation of HO-1 mRNA as measured by quantitative
      RT-PCR. This upregulation could also be demonstrated on the protein level.
      CONCLUSION: Aqueous extracts of the Tibetan herbal preparation Padma 28 inhibit
      CRP-induced expression of the inflammatory cell adhesion molecule E-selectin and
      lead to upregulation of the vascular protective enzyme HO-1 in human aortic
      endothelial cells. These properties may be responsible for its anti
      atherosclerotic effects in peripheral arterial occlusive disease.

PMID- 16582559
TI  - Antiproliferative properties of Padma Lax and its components ginger and
      elecampane.
AB  - BACKGROUND: Padma Lax (PL) is a multi-component herbal laxative, derived from
      traditional Tibetan medicine. It has been used in the treatment of constipation
      dominant irritable bowel syndrome. Beyond its purgative and bowel-regulating
      properties we found it to exhibit antiproliferative properties. MATERIALS AND
      METHODS: C6 tumor cells were incubated with either an ethanolic or aqueous
      extract of PL. Cell proliferation, cell cycle, percentage of apoptotic cells,
      caspase-3/-7 activity as well as mitochondrial membrane potential were
      determined. RESULTS: Ethanolic extracts of PL inhibited cell proliferation in a
      dose- and time-dependent manner (half max concentration: 384.4 mug/ml after 48 h
      of incubation). Aqueous extracts were less effective. Ginger and elecampane were
      the active components of PL in respect to its antiproliferative action and were
      found to act synergistically. Supplementing the culture medium with polyamines
      could not override the cytostatic action of PL. Incubation of C6 cells with PL in
      the presence of catalase proved that the PL effect was specific and not due to
      oxidative stress. PL had no effects on the cell cycle at a low dose but arrested
      cells in G1 at high concentrations. Reduction of cell numbers was found to be due
      to apoptosis. The caspase- 3/-7 pathway was not involved in the PL-induced cell
      death. However, mitochondrial membrane potential was lost during the course of
      incubation with PL indicating a mitochondrial- but not caspase-mediated induction
      of apoptosis. CONCLUSION: PL exhibits antiproliferative properties which may be
      beneficial to prevent constipation-related cancer. This study may also contribute
      to a future development of a new herbal-based antiproliferative treatment.

PMID- 16582560
TI  - [Efficacy and safety of Padma 28 in peripheral arterial occlusive disease].
AB  - BACKGROUND: The multicompound herbal drug Padma 28 is based on a formula from
      Tibetan Medicine and has been used in Switzerland for over 30 years in the
      symptomatic treatment of circulatory disorders including intermittent
      claudication. OBJECTIVE: What is the current evidence regarding the clinical
      efficacy and safety of this drug in patients with peripheral arterial occlusive
      disease(PAOD)? MATERIALS AND METHODS: Electronic databases were searched (each
      from inception to fall 2005) as well as the reference lists of the relevant
      articles. RESULTS: 14 articles were found including 6 published studies, 1 un
      published study, 6 double publications and 1 meta-analysis. Six studies analyzed
      maximum walking distance, 5 of these showed a significant increase. The pooled
      data of the meta-analysis confirmed a significant and clinically relevant
      increase of the maximum walking distance by more than 100 m in about 1 out of 5
      patients. Serious adverse events were not related to verum, non-serious adverse
      events were equally frequent as under placebo. CONCLUSIONS: The evidence
      available shows that the multi-target therapy with Padma 28 provides
      statistically significant and clinically relevant relief from PAOD-related
      symptoms, i.e. an increased walking distance.

PMID- 16582561
TI  - [Padma 28 in the treatment of chronic dental pulpitis: an observational case
      study in 49 patients].
AB  - BACKGROUND: In the case of pulpitis the dentist has to differentiate between a
      reversible and therefore treatable pulpal inflammation and an irreversible damage
      of the pulpa, accord-ing to the clinical symptoms. From these one cannot draw
      conclusions about the effective histological condition of the pulpa. Early stages
      of pulpitis cannot be recognized by X-rayeither. OBJECTIVES: By means of case
      studies in the course of daily dental practice the following questions are
      addressed:Is dental pulpitis an indication for the use of the Tibetan remedy
      Padma 28? Can a root canal treatment be prevented by administering Padma 28? What
      dosage is appropriate in this indication? PATIENTS AND METHODS: 53 patients with
      symptoms of chronic dental pulpitis but without clear indication for an im
      mediate root canal treatment were prescribed 2 x 2 tablets Padma 28 daily, for 15
      days. 49 patients took the preparation,and the course of symptoms was recorded
      and analyzed according to a simple scheme. RESULTS: 27 of these patients(55%)
      were free of pain within 1 month. A total of 40 patients(81%) reached a pain-free
      state after a longer period. By now, in most cases observations have been made
      for a period of 2-3 years (maximum: 5.5 years). 12 patients (24%) remained
      without relapse so far for more than 3 years. These experiences allow to deduce
      possible indications and clinical symptoms for the use of Padma 28. CONCLUSIONS:
      These results en-courage the use of Padma 28 as a complementary preparation with
      little side effects, in unclear cases of pulpitis. The clinical development can
      be observed without further treatment if the patient does not need pain
      medication. Most patients (>80%) showed a complete remission, positively affect
      ed and expedited by Padma 28; root canal treatments or ex-tractions could be
      prevented. In many cases the improvement has sustained over observation periods
      of >3 years. Criteria for therapeutic decisions are proposed.

PMID- 16582562
TI  - [Treatment of a tetraplegic patient with chronic constipation with the Tibetan
      remedy Padma Lax--a case report].
AB  - BACKGROUND: In spinal cord injuries disturbed defecation, constipation and their
      concomitant disorders are frequent clinical symptoms. They may severely impair
      the quality of life of the affected patients. The presented case study and two
      more case reports, summarized in table form, outline therapeutic difficulties and
      therapy options in the treatment of constipation in paraplegic patients. CASE
      REPORT: A 69-year-old male patient with tetraplegia below C4 suffered from
      disturbed defecation, constipation with recurrent co-prostasis and pronounced
      meteorism which impeded breathing. Padma Lax was applied for several months, and
      constipation and the concomitant meteorism were noticeably reduced. CONCLUSION:
      The herbal preparation based on a formula from Tibetan Medicine may offer new
      therapeutic options in the care and treatment of patients with severe
      constipation. This report could also give first indications for controlled
      clinical studies in tetraplegic patients.

PMID- 16582563
TI  - Visceral sliding technique is useful for detecting abdominal adhesion and
      preventing laparoscopic surgical complications.
AB  - STUDY OBJECTIVE: Introduce a non-invasive method preoperatively to prevent bowel
      injury by the Veres needle and trocar during laparoscopy. DESIGN: Case-controlled
      study. SETTING: A hospital-based study. PATIENTS: Five hundred and twelve
      patients who underwent laparoscopic surgery were prospectively enrolled.
      INTERVENTION: A simple and non-invasive method to detect bowel adhesions
      preoperatively. RESULTS: A total of 512 patients who underwent operative
      laparoscopy were prospectively enrolled for ultrasonographic visceral sliding
      evaluation. They were subdivided into two groups as follows: group I, 332
      patients without previous abdominal surgery; group II, 180 patients with previous
      abdominal surgery. No bowel adhesion to the umbilicus was present in group I. In
      group II, only two cases with bowel adhered to the periumbilical area were found
      by visceral sliding technique. No patients suffered any bowel injury. CONCLUSION:
      The proposed technique is useful and highly effective in guiding the insertion of
      the Veres needle and trocar to prevent bowel injury in laparoscopy.

PMID- 16582564
TI  - Growth hormone receptor sequence changes do not play a role in determining height
      in children with idiopathic short stature.
AB  - BACKGROUND/AIMS: In children with short stature, in whom growth hormone
      deficiency has been excluded, the presence of a normal or elevated growth hormone
      concentration concomitant with low insulin-like growth factor I suggests growth
      hormone insensitivity (GHI). Previous reports suggest that heterozygous mutations
      in the growth hormone receptor gene (GHR) may account for about 5% of children
      with idiopathic short stature (ISS). In the present study we have attempted to
      determine whether mutations in the GHR explain the short stature and growth
      retardation in a cohort of children with ISS and characteristics suggesting GHI.
      METHODS: For the present study 33 children with clinical and biochemical
      characteristics of GHI were selected from a cohort of 150 children of short
      stature. Molecular analysis of the GHR was performed using a single-strand
      conformation polymorphism technique and sequencing. Ten different sequence
      changes in 19 (58%) out of 33 children were identified, 9 of them novel and 1
      that had been described previously. RESULTS: Two changes were found in exons 2
      and 6. The known polymorphism of exon 6 (G168) was significantly more common in
      the control subjects than in our study group (63.5 vs. 30%; p < 0.0001). In the
      intronic sequences 8 previously undescribed DNA changes were found. The screening
      of the affected children's family members revealed that both normal and short
      stature members carried the same variants. The study group did not significantly
      differ from the controls in retention (GHRfl) or exclusion (GHRd3) of exon 3.
      CONCLUSION: Our study suggests that sequence changes of the GHR are common in
      children with ISS. The presence of these sequence changes in the control subjects
      as well as in normal stature family members indicates that these changes
      represent a simple polymorphism of the GHR. Such DNA changes are more prevalent
      than previously recognized, and they do not seem to play a contributory role in
      the etiology of short stature.

PMID- 16582565
TI  - Congenital hyperthyroidism: the fetus as a patient.
AB  - Congenital hyperthyroidism is less frequent than congenital hypothyroidism but
      its impact on growth and development can be as dramatic. The immune form of
      hyperthyroidism that is transmitted from a mother with Graves' disease to her
      foetus and then neonate is transient, but cases of persistent congenital
      hyperthyroidism had also been described, that can now be explained by molecular
      abnormalities of the thyrotropin receptor. The abundance of published data on the
      neonatal effects of maternal Graves' disease contrasts with the paucity of
      information on fetal effects. Recent studies showed that it is of utmost to
      scrutinize fetal thyroid by expert ultrasonographist and to have a team work with
      obstetricians and pediatric endocrinologists in pregnant women with Graves'
      disease. This allowed to accurately determine the fetal thyroid status and to
      adapt the treatment in the mothers successfully. Fetal hyperthyroidism does exist
      and needs an appropriate aggressive treatment. Clearly the fetus has become our
      patient!

PMID- 16582566
TI  - The effects of growth hormone treatment on health-related quality of life in
      children.
AB  - BACKGROUND/AIMS: The effects of growth hormone deficiency (GHD) on linear growth
      in children are well documented, but there is less convincing evidence regarding
      the impact on health-related quality of life (QOL). We examined QOL in children
      aged 8-16 years with acquired GHD following treatment for malignancy (AGHD) or
      idiopathic GHD (IGHD) on commencing growth hormone treatment (GHT) over 6 months.
      We adopted a longitudinal design involving consecutive patients and their
      families attending clinic over an 18-month period. Mothers and children were
      invited to complete questionnaires before GHT (T1) and 6 months later (T2).
      METHODS: Mothers of 22 children (AGHD n = 14; IGHD n = 8) completed standardized
      measures of child QOL and behaviour. Children completed parallel measures of QOL,
      short-term memory tasks and fitness either in clinic or at the family home.
      RESULTS: For children with AGHD, QOL was significantly below population norms at
      T1 and improved over time. For children diagnosed with IGHD, QOL at T1 was below,
      but comparable with population norms. QOL improved over time, though not
      significantly. CONCLUSION: GHT is potentially valuable for improving QOL in
      children, especially in cases of AGHD. We conclude that benefits of GHT for QOL
      need to be evaluated independent of different diagnostic groups.

PMID- 16582567
TI  - Health-related quality of life as a primary endpoint for growth hormone therapy.

PMID- 16582568
TI  - Insulin allergy and extensive lipoatrophy in child with type 1 diabetes.
AB  - Insulin allergy and lipoatrophy in type 1 diabetic patients have been previously
      reported but the mechanisms are not well documented. Here, we report a case
      emphasizing the role of abnormal local immune reaction associated with cytokine
      hyper production. The patient is a 7-year-old boy with a familial history of
      common variable immunodeficiency. Eight months after the diagnosis of type 1
      diabetes, he developed signs of insulin allergy expressed as continuously
      extensive and profound lipoatrophy contrasting with a well-preserved metabolic
      control. Specific insulin allergy was confirmed by skin prick tests that showed
      lymphoid activated cells in the subcutaneous tissue at the site of insulin
      injection. All therapies reported in the literature (antihistaminic, local
      steroid, change to lispro insulin, immunosuppressive treatment, subcutaneous
      insulin pump, peritoneal insulin infusion) were not efficient. It is suggested
      that familial disorders of immune cell functions with abnormal and excessive
      cytokine production might explain these adverse effects triggered by insulin with
      severe allergic reactions and lipoatrophy.

PMID- 16582569
TI  - Gonadotropin secretion in girls with turner syndrome measured by an
      ultrasensitive immunochemiluminometric assay.
AB  - BACKGROUND/AIM: Gonadotropin levels measured by radioimmunoassays are high in
      girls with Turner syndrome (TS), but overlap significantly with those of normal
      girls. We hypothesized that gonadotropin levels would be above the normal range
      in TS when measured by ultrasensitive assays. METHODS: Follicle-stimulating
      hormone (FSH) and luteinizing hormone (LH) levels were measured in 68 TS, and 133
      control girls using ultrasensitive immunochemiluminometric assays (ICMA).
      RESULTS: FSH levels in TS and normal girls were highest in early childhood (56.0
      +/- 39.7 and 2.3 +/- 1.8 IU/l, respectively), declined at 6-10 years of age (11.3
      +/- 13.1 and 1.8 +/- 0.9 IU/l, respectively), and then increased again (104.4 +/-
      68.9 and 4.9 +/- 2.4 IU/l, respectively). FSH was in the normal range on 11 of 27
      occasions in TS girls with ages 5-10 years, and on 3 of 44 occasions in >10
      years. Although average LH values were higher than those of controls, they often
      overlapped the normal range. CONCLUSION: A significant number of TS girls have
      normal gonadotropins by ICMA. Spontaneous gonadotropin levels are not an adequate
      screening test for the diagnosis of TS but may prove useful for predicting the
      gonadal function and determining the appropriate timing of estrogen replacement
      therapy.

PMID- 16582570
TI  - Sensori-neural deafness and hypothyroidism: autoimmunity causing 'pseudo-Pendred
      syndrome'.
AB  - Male, dizygotic twins were diagnosed with sensori-neural deafness at ages 5 and
      21 months and later developed hypothyroidism at ages 24 and 28 months,
      respectively. Analysis for anti-DEP-1/CD148 autoantibodies described in Cogan
      syndrome proved positive. As these antibodies are directed against endothelial
      cells as well as sensory epithelial cells the children need long-term monitoring
      for associated complications.

PMID- 16582571
TI  - Metabolic syndrome as a risk factor for contrast-induced nephropathy in non
      diabetic elderly patients with renal impairment.
AB  - BACKGROUND/AIMS: Metabolic syndrome (MS) as a risk factor for contrast-induced
      nephropathy (CIN) has not been studied. The aim of the present study was to
      assess the influence of MS on the development of CIN in patients undergoing
      coronary angiography. METHODS: This was a prospective cohort study. A total of
      219 non-diabetic patients with reduced kidney function and age >or=60 years were
      divided into two groups (MS, n = 107 and non-MS, n = 112). CIN was defined as an
      increase of >or=25% in creatinine over the baseline value within 48 h of
      angiography. RESULTS: CIN occurred in 14% of the MS group and 3.6% of the non-MS
      group (p = 0.006). Serum creatinine increased from 1.06 +/- 0.17 to 1.12 +/- 0.27
      mg/dl in the MS group and from 1.03 +/- 0.17 to 1.09 +/- 0.23 mg/dl in the non-MS
      group (p < 0.001). MS was a risk indicator of CIN [odds ratio (OR) 4.26; 95%
      confidence interval (95% CI) 1.19-15.25; p = 0.026). Impaired fasting glucose (OR
      4.72; 95% CI 1.53-14.56; p = 0.007), high triglyceride (OR 4.06; 95% CI 1.22
      13.44; p = 0.022), and multivessel involvement (OR 3.14; 95% CI 1.07-9.82; p =
      0.038) in the MS group were predictors of CIN. CONCLUSION: Our data support the
      hypothesis that patients with MS are at risk of developing CIN.

PMID- 16582572
TI  - Relation between different treatment modalities and genomic damage of end-stage
      renal failure patients.
AB  - BACKGROUND: Patients with end-stage renal disease display enhanced genomic
      damage. We investigated the relation between genomic damage and different
      treatment modalities. METHODS: In a longitudinal study two groups of patients
      were analyzed in monthly intervals. We assessed the initiation of hemodialysis in
      5 conservatively treated patients, and a switch from hemodialysis to
      hemodiafiltration in 7 patients. DNA damage was investigated in peripheral blood
      lymphocytes by micronucleus frequency and by comet assay analysis. With regard to
      potential genotoxicity of advanced glycation end products (AGEs), levels of
      imidazolone A and AGE-associated fluorescence (AGE-FL) were determined. RESULTS:
      The initiation of hemodialysis did not alter the genomic damage. In patients who
      switched from hemodialysis to hemodiafiltration, a small but significant
      reduction in the comet assay but not in the micronucleus frequency was observed.
      Elevated plasma levels of imidazolone A and AGE-FL were not influenced by the
      treatment modalities. CONCLUSION: In our small patient group no major reduction
      of the elevated genomic damage could be reached. Disease factors not influenced
      by altered dialysis modalities may have contributed considerably in our patient
      group. The persisting high levels of DNA damage suggest a need for further
      improvement. Inhibiting AGE formation may be one promising way for the future.

PMID- 16582573
TI  - Increased expression of renal aquaporin water channels in spontaneously
      hypertensive rats.
AB  - AIMS: The present study was aimed to determine whether there exists an altered
      regulation of aquaporin (AQP) water channels in hypertension. METHODS: Male
      spontaneously hypertensive rats (SHR) aged 10-12 weeks were used. Age-matched
      Wistar-Kyoto (WKY) rats served as control. The abundance of AQP1-4 proteins in
      the kidney was determined by Western blot analysis. The protein expression and
      activity of adenylyl cyclase were also determined. RESULTS: The medullary
      expression of AQP2 and AQP3 proteins was increased in SHR compared with that in
      WKY rats. The expression of AQP1 protein was also significantly increased in the
      inner medulla, while that of AQP4 was not. Immunohistochemistry of AQP2 revealed
      that principal cells of the collecting duct have strong immunoreactivity, the
      degree of which was augmented with prominent apical labeling in SHR. The plasma
      level of arginine vasopressin (AVP) was higher in SHR; the adenylyl cyclase
      activity stimulated by AVP was augmented, along with increased expression of type
      VI adenylyl cyclase. The urine was more concentrated with its volume decreased in
      SHR. CONCLUSION: The expression of AQP1-3 channels is increased in the kidney, in
      association with enhanced activity of the AVP/cAMP pathway, in SHR.

PMID- 16582574
TI  - Endothelial progenitor cells in chronic renal insufficiency.
AB  - There is growing evidence for a role of endothelial progenitor cells (EPCs) in
      the repair of damaged endothelium. It remains unclear which cell populations are
      most useful for clinical trials. Administration of drugs increasing EPC numbers
      and/or improving functional properties seems attractive. Further basic research
      is necessary to understand the mechanisms of mobilization, differentiation and
      homing of EPC in general and in particular under uremic conditions. Nephrologists
      should search for strategies to ameliorate EPC dysfunction of uremia. In this way
      it might be possible to test whether improved EPC biology is associated with
      decreased cardiovascular mortality in uremic humans. In any such studies the
      difficulties are going to be related to the complex procedures for EPC isolation,
      the testing of their identity and differentiation and their propagation before
      use.

PMID- 16582575
TI  - Cystatin C--a marker for assessment of the glomerular filtration rate in patients
      with cisplatin chemotherapy.
AB  - BACKGROUND: Cystatin C has recently been proposed as an ideal marker for
      glomerular filtration rate (GFR). In this study, cystatin C serum levels were
      evaluated in comparison to serum creatinine concentrations and inulin clearances
      in patients with normal kidney function receiving cisplatin-based chemotherapy to
      assess the validity of cystatin C as an alternative endogenous marker of GFR.
      METHODS: Blood samples for the assessment of cystatin C, creatinine and inulin
      clearances were collected in patients before and after application of cisplatin
      in a clinical trial. Overall, 41 patients were included in the study, 35 of them
      were eligible receiving cisplatin in two different cisplatin-based chemotherapy
      schedules. RESULTS: A 21% increase of cystatin C serum levels was demonstrated in
      the placebo group after application of cisplatin. Analysis of inulin clearances
      revealed a 23% loss of inulin clearance in patients of the placebo arm. In
      contrast, significant changes could not be detected by analysis of serum
      creatinine levels. CONCLUSIONS: Cystatin C represents a more sensitive clinical
      marker than serum creatinine for the early assessment of GFR damage caused by
      cisplatin. Changes in cystatin C serum concentrations correlate well to GFR
      decrease as measured by inulin clearance.

PMID- 16582576
TI  - Mice lacking protein kinase C beta present modest increases in systolic blood
      pressure and NH4Cl-induced metabolic acidosis.
AB  - The conventional protein kinase C isoenzyme beta (PKC-beta) is expressed in
      various structures of mouse kidney. To get insights into the function, PKC-beta
      knockout (-/-) and wild-type (+/+) mice were studied. Under basal conditions, PKC
      beta-/- mice exhibited a higher systolic blood pressure (in awake mice), normal
      plasma concentrations of Na+ and K+, and normal plasma pH. Urine osmolality and
      24-hour excretion of fluid, Na+, K+ and albumin were not different between
      genotypes, but urine pH was more alkaline in PKC-beta-/- mice. Inulin clearance
      experiments under anesthesia confirmed a higher systolic blood pressure and
      revealed normal glomerular filtration rate and fractional excretion of fluid, Na+
      and K+ in PKC-beta-/- mice. The ability to restrict renal Na+ excretion in
      response to a low Na+ diet was unaltered in PKC-beta-/- mice. Chronic acid
      loading (NH4Cl) did not affect blood pH in PKC-beta+/+ mice, but induced a modest
      metabolic acidosis in PKC-beta-/- mice. In conclusion, first evidence is
      presented that (i) PKC-beta contributes to the regulation of arterial blood
      pressure, and (ii) PKC-beta is required for normal acid-base balance, which may
      relate to its expression and function in intercalated cells of the collecting
      duct.

PMID- 16582577
TI  - Recapitulation of embryological programmes in renal fibrosis--the importance of
      epithelial cell plasticity and developmental genes.
AB  - Chronic fibrosis represents the final common pathway in progressive renal
      disease. Myofibroblasts deposit the constituents of renal scar, thus crippling
      renal function. It has recently emerged that an important source of these pivotal
      effector cells is the injured renal epithelium. This review concentrates on the
      process of epithelial-mesenchymal transition (EMT) and its regulation. The role
      of the developmental gene, gremlin, which is reactivated in adult renal disease,
      is the subject of particular focus. This member of the cysteine knot protein
      superfamily is critical to the process of nephrogenesis but quiescent in normal
      adult kidney. There is increasing evidence that gremlin expression reactivates in
      diabetic nephropathy, and in the diseased fibrotic kidney per se. Known to
      antagonize members of the bone morphogenic protein (BMP) family, gremlin may also
      act downstream of TGF-beta in induction of EMT. An increased understanding of the
      extracellular modulation of EMT and, in particular, of the gremlin-BMP axis may
      result in strategies that can halt or reverse the devastating progression of
      chronic renal fibrosis.

PMID- 16582579
TI  - Antibodies for targeted cancer therapy -- technical aspects and clinical
      perspectives.
AB  - The efficacy of traditional anti-cancer agents comes with the price of toxicity
      to normal cells, which limits the success of therapy. In the past 2 decades,
      greater understanding of the molecular differences between malignant and normal
      cells has led to the development of therapies that more specifically target human
      tumors. These include new anti-cancer agents directed against intracellular
      targets associated with malignant alterations, such as increased proliferation,
      impaired apoptosis or angiogenesis. In addition, antibodies have been developed
      that are directed towards tumor-associated antigens and provide tailor-made
      effector functions by inhibiting cell growth, inducing apoptosis or constituting
      cytotoxic drug delivery systems. Since the targeted approach of anti-cancer
      therapies increases the exposure of malignant cells and at the same time reduces
      the exposure of normal tissues, it offers the promise of enhanced efficacy and
      lower side effects. Antibodies, immunoconjugates and liposomal drug delivery
      systems derived thereof are now mainstream cancer therapeutics, and by the end of
      2003 17 marketed antibody-based products generated several billion in combined
      annual sales. This study highlights the most recent breakthroughs in antibody
      technology and summarizes major achievements in antibody-based cancer therapy in
      oncology trials.

PMID- 16582578
TI  - Interactions between angiotensin ll and atrial natriuretic peptide in
      renomedullary interstitial cells: the role of neutral endopeptidase.
AB  - BACKGROUND/AIMS: Neutral endopeptidase (NEP) inhibition attenuates renal damage
      in the diabetic kidney, but little is known about the mechanisms of this
      renoprotective effect. METHODS: We examined the interaction between angiotensin
      II (Ang II) and atrial natriuretic peptide (ANP) under low (5 mM) and high (30
      mM) glucose conditions, on cell proliferation and extracellular matrix (ECM)
      synthesis in renomedullary interstitial cells (RMICs) derived from wild-type (WT)
      and NEP-deficient (NEP-) mice. RESULTS: Under high glucose conditions, Ang II
      (10(-6)M) increased cell proliferation (control, 174.3 +/- 16.9; Ang II, 846.3 +/
      91.0 cpm/well) and ECM synthesis (control, 22.3 +/- 3.1; Ang II, 79.0 +/- 9.6
      cpm/cell) in RMICs derived from WT and NEP- mice to a similar extent. ANP (10(
      7)M) reduced Ang II-induced cell proliferation and ECM synthesis in RMICs derived
      from both strains, but more efficiently in RMICs derived from NEP- mice. The Ang
      II-induced cell proliferation and ECM synthesis was attenuated with AT1 receptor
      blockade, but more efficiently in RMICs-derived NEP- mice. CONCLUSIONS: This data
      shows that ANP and AT1 receptor blockade attenuate Ang II-induced RMIC
      proliferation and ECM synthesis more efficiently in the absence of NEP. These
      results support the concept that NEP inhibition is beneficial in attenuating
      abnormal cell growth and ECM metabolism associated with diabetic nephropathy.

PMID- 16582580
TI  - Anti-interleukin-5 antibody therapy in eosinophilic diseases.
AB  - Eosinophilia in atopic diseases and hypereosinophilic syndrome is often
      associated with a high expression of interleukin-5 (IL-5). IL-5 plays an
      important role in regulating the production, differentiation, recruitment,
      activation, and survival of eosinophils. Therefore, neutralizing IL-5 with an
      antibody is a promising therapeutic strategy in eosinophilic diseases. In
      patients with hypereosinophilic syndrome and eosinophilic esophagitis, anti-IL-5
      antibody therapy resulted in an improvement of symptoms. In patients with
      bronchial asthma, no effect on the late phase reaction and on airway
      hyperresponsiveness has been observed. Moreover, patients with atopic dermatitis
      demonstrated only a moderate improvement of their skin lesions and pruritus. Anti
      IL-5 therapy was followed by a rapid and sustained decrease of peripheral blood
      eosinophil numbers. The decrease of tissue eosinophils was, however, less
      dramatic. Investigating the effects of anti-IL-5 therapy will improve our
      understanding of the pathogenic roles of both IL-5 and eosinophils in
      eosinophilic inflammatory responses.

PMID- 16582581
TI  - Environment as a critical factor for the pathogenesis and outcome of
      gastrointestinal disease: experimental and human inflammatory bowel disease and
      helicobacter-induced gastritis.
AB  - Environmental factors play an important role in the manifestation, course, and
      prognosis of diseases of the gastrointestinal tract such as inflammatory bowel
      disease (IBD) and Helicobacter pylori-induced gastritis. These two disease
      complexes were chosen for a discussion of the contribution of environmental
      factors to the disease outcome in humans and animal models. Dissecting complex
      diseases like IBD and Helicobacter-induced gastritis has shown that the outcome
      of disease depends on the allelic constellation of a host and the microbial and
      physical environments. Host alleles predisposing to a disease in one genomic
      and/or environmental milieu may not be deleterious in other constellations; on
      the other hand, microbes can have different effects in different hosts and under
      different environmental conditions. The impact of the complex interaction between
      host genetics and environmental factors, particularly microflora, also underlines
      the importance of a defined genetic background and defined environments in animal
      studies and is indicative of the difficulties in analyzing complex diseases in
      humans.

PMID- 16582582
TI  - Leukocyte infiltration of the periarterial space of the lung after allergen
      provocation in a rat asthma model.
AB  - The periarterial space has recently been described and its physiological and
      pathophysiological role during inflammatory and allergic reactions has been
      reviewed. The present studies used a light-/electron-microscopic approach to
      characterize the periarterial space in an asthma model in Brown Norway rats.
      After repeated sensitization with ovalbumin and heat-killed Bordetella pertussis
      bacilli, airway challenge was carried out after 1 further week. Four or 24 h
      after challenge, rats were fixed by perfusion or instillation and processed for
      microscopy. Several periarterial capillaries and connective tissue characterized
      the tissue between small pulmonary arteries, bronchioles and alveolar septa.
      Additionally, a partly pronounced interstitial edema was seen independent of the
      kind of fixation. Not only small arteries but also arterioles and venules were
      partly surrounded by edematous fluid already visible by light microscopy. Within
      the connective tissue and within the periarterial fluid, numerous leukocytes,
      predominantly eosinophils, were found. However, leukocytes were detected only
      rarely in the vascular lumen. Only sporadically were eosinophils seen in the wall
      of small arteries or venules. Eosinophils transmigrating the endothelium of
      capillaries or arterioles were not visible 4 or 24 h after challenge. Thus,
      granulocytes transmigrate in the periarterial space very rapidly or even earlier
      than 4 h after challenge. The location of transmigration in the periarterial
      space needs further investigation.

PMID- 16582583
TI  - Expression of RUNX3 protein in human esophageal mucosa and squamous cell
      carcinoma.
AB  - Runt-related transcriptional factor gene 3 (RUNX3) belongs to the runt domain
      family of transcriptional factors that plays an important role during normal
      tissue development and in tumorigenesis in several organs. This study examined
      the expression of RUNX3 protein in human esophageal mucosa and squamous cell
      carcinoma in comparison with clinicopathological profiles. Western blot analysis
      and RT-PCR revealed that both RUNX3/P44 and P27, but not P46, were expressed in
      all three human esophageal squamous cell carcinoma (SCC) cell lines, as well as
      in three pairs of esophageal SCC cell lines and the corresponding nontumoral
      mucosa specimens. RUNX3 expression was shown in prickle and functional cell layer
      cells in normal esophageal mucosa. On the other hand, immunoreactivity was seen
      only in carcinoma cells around the cancer pearls. RUNX3 expression was
      significantly higher in the 19 well-differentiated SCCs than in the 56 moderately
      or 69 poorly differentiated SCCs (p < 0.01). The 3-year survival rate was
      significantly lower in the 29 patients with lower RUNX3 expression than in the 37
      patients with higher expression (p = 0.0003). These results indicated that RUNX3
      protein might play an important role in cellular differentiation in both
      esophageal mucosa and SCC. The expression correlated with the patients' prolonged
      survival, implying a tumor suppressive effect in esophageal SCCs.

PMID- 16582584
TI  - The antiatherogenic effect of allicin: possible mode of action.
AB  - OBJECTIVE: Garlic (Allium sativum) has been suggested to affect several
      cardiovascular risk factors. Its antiatherosclerotic properties are mainly
      attributed to allicin that is produced upon crushing of the garlic clove. Most
      previous studies used various garlic preparations in which allicin levels were
      not well defined. In the present study, we evaluated the effects of pure allicin
      on atherogenesis in experimental mouse models. METHODS AND RESULTS: Daily dietary
      supplement of allicin, 9 mg/kg body weight, reduced the atherosclerotic plaque
      area by 68.9 and 56.8% in apolipoprotein E-deficient and low-density lipoprotein
      (LDL) receptor knockout mice, respectively, as compared with control mice. LDL
      isolated from allicin-treated groups was more resistant to CuSO(4)-induced
      oxidation ex vivo than LDL isolated from control mice. Incubation of mouse plasma
      with (3)H-labeled allicin showed binding of allicin to lipoproteins. By using
      electron spin resonance, we demonstrated reduced Cu(2+) binding to LDL following
      allicin treatment. LDL treatment with allicin significantly inhibited both native
      LDL and oxidized LDL degradation by isolated mouse macrophages. CONCLUSIONS: By
      using a pure allicin preparation, we were able to show that allicin may affect
      atherosclerosis not only by acting as an antioxidant, but also by other
      mechanisms, such as lipoprotein modification and inhibition of LDL uptake and
      degradation by macrophages.

PMID- 16582585
TI  - Overexpression of PrPC and its antiapoptosis function in gastric cancer.
AB  - Cellular prion protein (PrP(C)), a glycosylphosphatidylinositol-anchored membrane
      protein, was found in our lab to be widely expressed in gastric cancer cell
      lines. In order to evaluate its biological significance in human gastric cancer,
      we investigated its expression in a large series of gastric tissue samples (n =
      124) by immuno histochemical staining with the monoclonal antibody 3F4. Compared
      with normal tissues, gastric adenocarcinoma showed increased PrP(C) expression,
      correlated with the histopathological differentiation (according to the WHO and
      Lauren classifications) and tumor progression (as documented by pTNM staging). To
      better understand the underlying mechanism, we introduced the PrP(C) and two
      pairs of RNAi into the poorly differentiated gastric cancer cell line AGS and
      found that PrP(C) suppressed ROS and slowed down apoptosis in transfected cells.
      Further study proved that the apoptosis-related protein Bcl-2 was upregulated
      whereas p53 and Bax were downregulated in the PrP(C)-transfected cells. A reverse
      effect was observed in PrP(C) siRNA-transfected cells. These results strongly
      suggested that PrP(C) might play a role as an effective antiapoptotic protein
      through Bcl-2-dependent apoptotic pathways in gastric cancer cells. Further study
      into the mechanism of these relationships might enrich the knowledge of PrP,
      better our understanding of the nature of gastric carcinoma, and further develop
      possible strategies to block or reverse the development of gastric carcinoma.

PMID- 16582586
TI  - Mechanisms of the synergistic interaction between the bisphosphonate zoledronic
      acid and the chemotherapy agent paclitaxel in breast cancer cells in vitro.
AB  - Breast cancer patients often receive both paclitaxel and zoledronic acid as part
      of their treatment, and these drugs are reported to have synergistic effects on
      the induction of apoptosis of breast cancer cells in vitro. We have found that
      the synergistic interaction is drug sequence dependent, with maximal levels of
      apoptosis achieved when cells are treated with paclitaxel followed by zoledronic
      acid, as opposed to the reverse sequence or simultaneous treatment. The
      synergistic interaction persists at clinically relevant concentrations and
      incubation periods. We report that the sequential treatment is associated with
      cell cycle changes and depends on breast cancer cell characteristics, with
      hormone independence, mutated p53 status and presence of BRCA1 gene being
      associated with higher levels of apoptosis. Finally, we have found that the
      synergistic induction of apoptosis is via zoledronic acid-mediated inhibition of
      the mevalonate pathway.

PMID- 16582587
TI  - A late origin of DNA replication in the trinucleotide repeat region of the human
      FMR2 gene.
AB  - We confirmed that the replication of the fragile-X E site (FRAXE) in human
      chromosomal band Xq28 occurs at six hours into the eight-hour S phase of normal
      human fibroblasts. In this late-replicating region, we mapped an origin of DNA
      replication within the promoter of FMR2. This origin is coincident with CpG
      islands, the trinucleotide repeat, and exon 1 of the FMR2 gene. Identification of
      this origin may aid in the investigation of the mechanism of trinucleotide repeat
      expansion and its effect on FMR2 expression. In addition, knowledge of the
      chromosomal locations and sequence characteristics of both early and late origins
      of DNA replication, such as the one described in this report, will facilitate
      studies of the molecular determinants of the time of activation of different
      origins of replication and allow us to refine our insights concerning origin
      inactivation in response to the DNA damage-induced intra-S checkpoint.

PMID- 16582588
TI  - CARD tricks: controlling the interactions of CARD6 with RICK and microtubules.
AB  - In recent years, a number of proteins have been identified that contain a
      homotypic interaction motif called the caspase recruitment domain (CARD). Most
      proteins containing a CARD are involved in pathways regulating apoptosis or
      adaptive or innate immunity. Examples of prominent CARD proteins are caspase-9
      and Apaf1, which are involved in the intrinsic death pathway; BCL10 and CARD11,
      which mediate antigen receptor-induced NF-kappaB activation; and receptor
      interacting protein (RIP)-like interacting caspase-like apoptosis regulatory
      protein kinase (RICK) and the nucleotide-binding oligomerization domain (NOD)
      proteins, which induce NF-kappaB activation in response to intracellular
      bacterial peptidoglycan. The most recently discovered pathway involving CARD
      proteins senses virally-derived double-stranded (ds) RNA and initiates a host
      defense signaling program. CARD6 is a CARD-containing protein with a domain
      structure not shared by any other CARD protein. Although the CARD6 cDNA was
      deposited in GenBank five years ago, the physiological function of full-length
      CARD6 has yet to be reported. Here we review our initial characterization of
      CARD6 and discuss the functional implications of various conserved modules found
      in the CARD6 protein sequence. We conclude that CARD6 is structurally and
      potentially functionally related to the superfamily of interferon (IFN)-inducible
      GTPases, a growing family of host defense proteins that confer cell-autonomous
      immunity.

PMID- 16582589
TI  - Oncogenes and the DNA damage response: Myc and E2F1 engage the ATM signaling
      pathway to activate p53 and induce apoptosis.
AB  - Activation of the ATM DNA damage response pathway is commonly observed in a
      variety of early-stage neoplasias. It has been proposed that this checkpoint
      response functions to suppress the development of cancer. A recent report from
      our laboratory demonstrates that ATM does indeed function to suppress
      tumorigenesis by responding to at least some oncogenic stresses. Transgenic
      expression of Myc is found to cause DNA damage in vivo and ATM is shown to
      respond to this damage by inducing the accumulation and phosphorylation of p53.
      In the absence of ATM, p53-dependent apoptosis is reduced and epithelial
      tumorigenesis is accelerated in Myc transgenic mice. Deregulated expression of
      the E2F1 transcription factor also elicits an ATM-dependent checkpoint response
      that activates p53 and promotes apoptosis, although the mechanism by which E2F1
      and Myc stimulate ATM may differ. These findings have relevance for understanding
      why the ATM pathway is activated in many human cancers, what generates the
      selective pressure for p53 inactivation during tumorigenesis, and why AT patients
      and carriers are predisposed to developing cancer.

PMID- 16582590
TI  - TRAF3: a new regulator of type I interferons.
AB  - Type I interferons are a major and essential component of the mammalian antiviral
      response. While many cell types produce type I interferons following viral
      infection, how cells detect the virus has remained a mystery for many years.
      Recently, multiple genome-encoded viral recognition receptors have been
      identified. Interestingly, all of the major viral recognition pathways
      characterized thus far require TRAF3 to initiate type I interferon production. In
      this review, we comment on the mechanistic and biological implications for the
      new role of TRAF3 in innate antiviral immunity.

PMID- 16582592
TI  - Anti-tumor effects of the bacterium Caulobacter crescentus in murine tumor
      models.
AB  - Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in
      aquatic and soil environments. One feature of note is a protein surface layer (S
      layer) composed of a single protein, organized as a self-assembled crystalline
      array that coats the bacterium. In the course of efforts to express cancer
      associated peptides as genetic insertions into the S-layer, we noted a tumor
      suppressive effect of the unmodified bacterium. C. crescentus was examined for
      anti-tumor activity against three transplantable tumor mouse models: Lewis lung
      carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary
      carcinoma (EMT-6) in BALB/c (both in prophylactic and therapeutic mode) and
      murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with
      C. crescentus (2 x 10(7) cells/mouse). In prophylactic mode, the mice were
      challenged with tumor cells two weeks after the last immunization. Immunization
      with live C. crescentus resulted in anti-tumor activity in all three
      transplantable tumor models, as measured by prolonged survival, reduced tumor
      mass or reduced number of lung nodules, compared to saline control groups. In the
      Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung
      nodules as well as the tumor weight was lower in mice treated with C. crescentus,
      compared to the control group; for EMT-6, this was observed in prophylactic and
      therapeutic modes. In the murine leukemia and Lewis lung carcinoma models
      prolonged survival was observed in the groups of mice immunized with
      Caulobacters. In most cases the live C. crescentus cells were markedly more
      efficacious than heat killed or formalin fixed cells, despite the fact that they
      do not grow or persist in mice. The results suggest that C. crescentus may be a
      safe, bacterial immunomodulator for the treatment of tumors.

PMID- 16582591
TI  - Nicotinic receptors mediate tumorigenic action of tobacco-derived nitrosamines on
      immortalized oral epithelial cells.
AB  - Frequent users of smokeless tobacco (ST) have an increased risk for developing
      oral cancer. Nicotine and its derivatives may contribute to tumorigenesis through
      stimulation of nicotinic acetylcholine receptors (nAChRs) in target cells.
      Emerging evidence indicates that nAChRs can be stimulated by the nicotine-derived
      nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'
      nitrosonornicotine (NNN) that can induce oral cavity tumors in laboratory
      animals. This study was designed to elucidate the receptor-mediated mechanisms of
      the initiation and progression of NNK-, and NNN-induced oral cancers. We used Het
      1A cells that were found to express alpha3, alpha5, alpha7, alpha9, beta2 and
      beta4 nAChR subunits. Both NNK and NNN competed with nicotinic radioligands for
      binding to Het-1A cells. NNK showed a higher than NNN affinity to the
      [3H]nicotine-labeled binding sites, and NNN-to the [3H]epibatidine-sensitive
      nAChRs. NNK and NNN increased proliferative potential of Het-1A cells and
      produced an anti-apoptotic effect, which was alleviated by antagonists. alpha
      Bungarotoxin was most effective against NNK and mecamylamine against NNN.
      Treatment of Het-1A cells with either NNK or NNN led to acquisition of capability
      of anchorage independent growth and ability to produce tumors in nude mice, both
      of which can be by inhibited by antagonists. To elucidate the signaling
      mechanisms, we studied transcription of the genes encoding the cell cycle,
      apoptosis and signal transduction regulators at both the mRNA and protein levels.
      The Het-1A cells stimulated with nitrosamines showed multifold increases of the
      mRNA transcripts encoding PCNA and Bcl-2, and upregulated expression of the
      transcription factors GATA3, nuclear factor-kappaB, and STAT-1. The STAT-1
      protein-binding activity induced by NNK and NNN correlated with elevated gene
      expression. The obtained results establish the role of specific nAChR subtypes in
      tobacco-related carcinogenesis and open a novel avenue for oral cancer
      chemoprevention.

PMID- 16582593
TI  - Persistence of survivin specific T cells for seven years in a melanoma patient
      during complete remission.
AB  - Monitoring and evaluation of biological responses induced by immunotherapy may
      provide important information with regards to efficacy, side effects, and
      potential improvements of treatment. Herein, we describe results from monitoring
      of T cell reactivity against survivin derived peptides, in a melanoma patient in
      complete remission following IL-2 based immunotherapy. The patient remains in
      complete remission five years after completion of therapy. Long-time persistence
      of anti-tumor responses is rarely monitored, however, in the present patient
      longitudinal examination of anti-survivin reactivity exceeded seven years.
      Throughout, survivin reactivity was monitored both by INFgamma-ELISPOT as well as
      by flow cytometry using HLA-multimers. Survivin specific T cell reactivity was
      found at all time points examined over the 7-year period. Moreover, using these
      two methods, similar precursor frequencies was found indicating that the majority
      of the survivin specific T cells posses functional capabilities. Our data
      demonstrate that anti-survivin T cells may persist in the periphery for extended
      periods in the absence of clinical manifestation of disease as well as
      autoimmunity.

PMID- 16582594
TI  - Gefitinib accumulation in glioblastoma tissue.
AB  - Therapeutic agents for brain tumors confront multiple physical and metabolic
      hurdles. These include the blood brain barrier (BBB), vascular and interstitial
      barriers, clearing by MDR1 and other ABC transporter proteins, and drug
      catabolism. Here, we report an accumulation of gefitinib in glioblastoma (GBM)
      tissue to over a dozen times plasma levels, and propose that some mechanisms
      converge to achieve such accumulation: (1) small molecular size of gefitinib
      facilitates access by diffusion; (2) its high water solubility enables
      thermodynamic retention inside malignant cells; and (3) low CYP3A4 activity in
      GBM tissue, the main enzyme for gefitinib catabolism, prevents metabolic
      elimination. Our data confirm the capacity of gefitinib to accumulate in solid
      human tumors in vivo.

PMID- 16582595
TI  - Induction of GDF-15/NAG-1/MIC-1 in human lung carcinoma cells by retinoid-related
      molecules and assessment of its role in apoptosis.
AB  - Growth and Differentiation Factor-15 (GDF-15, NAG-1, MIC-1) is induced by several
      apoptosis-inducing agents including the retinoid-related molecule (RRM) 6-[3-(1
      adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437). It has been
      suggested that GDF-15 may be involved in the induction of apoptosis by CD437 in
      H460 lung cancer cells. The present study was designed to probe this hypothesis
      more directly. Several RRMs (CD437, ST1926 and MX3350-1) but not the retinoids
      all-trans- retinoic acid and 4HPR were able to induce GDF-15 in H460 cells. A
      similar differential effect of these retinoids was observed for the induction of
      p53, which has been reported to regulate GDF-15 expression. In H460 cells
      transfected with a neo vector control (H460-Neo), treatment with RRMs but not
      ATRA or 4HPR resulted in increases in p53, GDF-15 and apoptosis evidenced by
      poly(ADP ribose) polymerase (PARP) cleavage. In contrast, RRMs failed to increase
      p53 or induce apoptosis in H460 cells in which p53 was inactivated by
      transfection of the human papillomavirus E6-6 (H460-E6-6). The increase in GDF-15
      by RRMs was also compromised in the H460-E6-6 cells. Because PARP cleavage was
      only evident when GDF-15 levels where elevated it appeared that GDF-15 was
      mediating the pro-apoptotic effects of RRMs. However, silencing of GDF-15
      induction by RNA interference failed to decrease the ability of CD437 and ST1926
      to induce apoptosis. These results demonstrate that GDF-15 is dispensable for the
      pro-apoptotic activity of CD437 and ST1926.

PMID- 16582596
TI  - Mutational hotspot in exon 20 of PIK3CA in breast cancer among Singapore Chinese.
AB  - The recent identification of somatic mutations in the catalytic region of PIK3
      (PIK3CA) in breast cancer and demonstration of their oncogenic function has
      implicated PIK3CA in mammary carcinogenesis. To investigate possible ethnic
      differences in patterns of PIK3CA mutations in Singaporean Chinese breast cancer
      and to characterize these in a panel of cell lines, we sequenced exons 9 and 20
      in 80 primary tumors, 19 breast cancer cell lines and 7 normal human mammary
      epithelial cells (HMECs). Searching for novel hotspots of mutation, we sequenced
      additional exons (1, 2, 6, 7, 14 and 18) in 20 primary tumors and 6 breast cancer
      cell lines. We detected 33 point mutations in 31 of 80 (39%) breast cancers, and
      11 mutations in 10 of 19 (53%) breast cancer cell lines. No mutations were
      detected in normal breast tissue adjacent to the tumor, or in the 6 normal HMECs.
      The exon 20 A3140G (H1047R) substitution was identified most frequently (22/31,
      71%) and showed a significant association with patient age (p = 0.043) and stage
      of the disease (p = 0.025), but not with ER/PR status or histological grade of
      the tumor. The incidence of point mutations in PIK3CA, the A3140G substitution in
      particular, in Singapore breast cancers are among the most frequent reported to
      date for any gene in breast cancer. The results suggest that mutation of PIK3CA
      might contribute to development of early stage breast cancer and could provide a
      potent target for early diagnosis and therapy.

PMID- 16582597
TI  - EGFR-dependent downregulation of Bim in epithelial cells requires MAPK and PKC
      delta activities.
AB  - Activation of the epidermal growth factor receptor (EGFR) provides a measure of
      protection to immortalized epidermal keratinocytes (HaCaT cells) against
      apoptosis induced by diverse cellular stressors. This effect is due, in part, to
      sustained MAPK-dependent Bcl-xL expression. Here, we report a second EGFR/MAPK
      dependent signaling event that protects HaCaT cells against apoptosis incurred
      during forced suspension culture (anoikis). This pathway targets Bim, a pro
      apoptotic BH3-only Bcl-2 family member. Bim expression was functionally relevant
      to HaCaT cell survival as demonstrated by partial protection against anoikis
      provided by siRNA-induced Bim downregulation. Growth factor starvation of
      attached and suspended cells was associated with enhanced Bim expression whereas
      EGFR activation reduced Bim expression by inducing Bim phosphorylation and
      proteasomal degradation. EGFR-dependent Bim phosphorylation required MAPK
      activation. Furthermore, PKC-delta activity contributed to both MEK/MAPK
      phosphorylation and Bim phosphorylation as demonstrated using both
      pharmacological inhibitors of PKC-delta and siRNA-mediated PKC-delta knockdown.
      In addition to HaCaT cells, EGFR activation supported survival and induced Bim
      phosphorylation in several squamous carcinoma cell lines in a strictly MAPK
      dependent fashion. These results establish that EGFR activation attenuates
      susceptibility of immortalized and malignant keratinocytes to apoptosis by post
      translational control of Bim-EL expression through a pathway requiring PKC-delta
      and MEK/MAPK activation.

PMID- 16582598
TI  - Tumoral expression of BRCA1, estrogen receptor alpha and ID4 protein in patients
      with sporadic breast cancer.
AB  - INTRODUCTION: BRCA1 expression is downregulated in a third of sporadic breast
      cancers (SBC). Most of the tumors in which BRCA1 function is diminished do not
      express estrogen receptor alpha (ER). Recent studies suggest that the inhibitor
      of DNA binding (ID)-4 could participate in the hormonal regulation of BRCA1
      expression. OBJECTIVE: To study the relationship between tumoral expression of
      BRCA1, ER and ID4 in SBCs. PATIENTS AND METHODS: Forty patients with pathologic
      confirmation of SBC were included in this study. The mRNA expression of BRCA1, ER
      and ID4, determined by reverse transcription and polymerase chain reaction (RT
      PCR), was correlated with the expression of gliceraldehid-3-phosphate
      dehydrogenase (GAPDH). The results were analyzed using two-sided nonparametric
      tests (Chi-square and Spearman's rank correlation test) with alpha < 0.05.
      RESULTS: Most of the tumors that expressed BRCA1 mRNA were ER-positive (p <
      0.0001). In addition, a positive correlation was observed between the level of
      expression of these mRNAs (rs = 0.75 95% CI = 0.57-0.86; p < 0.0001). An inverse
      association was observed between the mRNA expression of BRCA1 and ID4 (p = 0.024)
      and a negative correlation between their levels of expression (rs = -0.35 95% CI 
      0.59 a -0.04; p = 0.028). Moreover, a negative correlation was stated between the
      level mRNAs of ER and ID4 (rs = - 0.45 95% CI -0.66 a -0.16; p = 0.0039).
      DISCUSSION: In this study we demonstrate an association between the tumoral
      expression of BRCA1, ER and ID4 in patients with SBC. These results are in
      concordance with previous studies, however, to our knowledge, no other reports
      have described a relationship between the expression of ID4 and ER at the mRNA
      level in human breast cancers. These results suggest that ID4 participates in the
      molecular events that regulate BRCA1 and ER expression, suggesting its role as a
      tumor marker or potential therapeutic target.

PMID- 16582599
TI  - Depletion of intracellular glutathione contributes to JNK-mediated death receptor
      5 upregulation and apoptosis induction by the novel synthetic triterpenoid methyl
      2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me).
AB  - The novel synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28
      oate (CDDO-Me) induces apoptosis in human cancer cells, showing potential as a
      cancer therapeutic agent. We previously demonstrated that CDDO-Me induces a c-Jun
      N-terminal kinase (JNK)-mediated DR5 expression and apoptosis. This study
      revealed the mechanism by which CDDO-Me induces JNK activation and subsequent DR5
      upregulation and apoptosis. To determine whether CDDO-Me activates JNK and
      induces DR5 expression and apoptosis via oxidative stress by inducing the
      generation of reactive oxygen species (ROS), we examined the effects of various
      antioxidants on JNK activation, DR5 upregulation, and apoptosis induction by CDDO
      Me. Thiol antioxidants, including N-acetyl-L-cycteine (NAC), glutathione (GSH)
      and dithiothrietol (DTT), abrogated CDDO-Me-induced apoptosis. In contrast,
      nonthiol antioxidants, including butylated hydroxyanisole (BHA), Trolox,
      mannitol, and Mn(II) tetra(4-benoic acid) porphyrin chloride (MnTBAP), failed to
      do so, with the exception of vitamin C (Vit C). Accordingly, only thiol
      antioxidants blocked JNK activation induced by CDDO-Me. CDDO-Me reduced
      intracellular levels of GSH; this reduction was abrogated only by thiol
      antioxidants and Vit C. However, CDDO-Me did not promote ROS generation. These
      results suggest that depletion of intracellular GSH, but not ROS generation,
      contributes to CDDO-Me-induced JNK activation and apoptosis, at least in our
      systems. Furthermore, these thiol antioxidants abrogated CDDO-Me-induced DR5
      expression, whereas the GSH-depleting agent diethylmaleate also upregulated DR5
      expression at concentrations that deplete intracellular GSH, demonstrating that
      GSH depletion can cause DR5 upregulation. Collectively, we conclude that CDDO-Me
      activates the JNK pathway via depletion of intracellular GSH, leading to DR5
      upregulation and induction of apoptosis.

PMID- 16582601
TI  - Cyclin e overexpression reduces infiltrative growth in breast cancer: yet another
      link between proliferation control and tumor invasion.
AB  - Overexpression of cyclin E is strongly linked to an aggressive phenotype and poor
      prognosis in breast cancer. Unexpectedly, it has been shown that cyclin E
      overexpression decreases mobility and invasiveness of breast cancer cells. In
      fact, in a study of 985 breast cancers, cyclin E correlated with less
      infiltrative growth. This suggests a novel function for cyclin E in breast cancer
      tumorigenesis and a mutual control of proliferation and invasive behavior.

PMID- 16582600
TI  - Revealing hidden relationships among yeast genes involved in chromosome
      segregation using systematic synthetic lethal and synthetic dosage lethal
      screens.
AB  - The vast accumulation of knowledge from genome sequencing projects and studies
      with model organisms has presented a remarkable challenge to biologists: to
      understand the functions of thousands of highly conserved genes and how they work
      together to regulate fundamental cellular processes. This challenge is compounded
      by the inescapable reality that most genes are 'buffered' by other genes that
      contribute to the same biological processes, limiting the impact of phenotypic
      studies with single mutants. In budding yeast, functional genomic methods have
      been developed for the systematic application of established genetic techniques.
      In particular, the Synthetic Genetic Array (SGA) method allows genome-wide
      synthetic lethal (SL) and synthetic dosage lethal (SDL) screens thus enabling an
      unbiased survey of genetic interactions. We have used genes encoding components
      of the yeast kinetochore as a biological testbed for assaying the utility of SGA
      based SL and SDL screens for revealing new pathways and genes involved in
      chromosome segregation. We identified 211 nonessential deletion mutants that were
      unable to tolerate either overexpression or loss of function of kinetochore
      genes. Our study uncovered a wealth of relationships between gene products that
      functionally interact with the kinetochore, and also highlighted the value of
      performing genome-wide screens with both hypomorphic and hypermorphic alleles of
      query genes. Here, we will highlight our recent kinetochore SGA genomic screens,
      in the broader context of applying complementary genetic screening approaches in
      the systematic exploration of biological pathways or functional complexes.

PMID- 16582602
TI  - Mammalian cyclin D1/Cdk4 complexes induce cell growth in Drosophila.
AB  - The Drosophila melanogaster cyclin dependent protein kinase complex CycD/Cdk4 has
      been shown to regulate cellular growth (accumulation of mass) as well as
      proliferation (cell cycle progression). In contrast, the orthologous mammalian
      complex has been shown to regulate cell cycle progression, but possible functions
      in growth control have not been addressed directly. To test whether mammalian
      Cyclin D1/Cdk4 complexes are capable of driving cell growth, we expressed such a
      complex in Drosophila. Using assays that distinguish between mass increase and
      cell cycle progression, we found that this complex stimulated cell growth, like
      its Drosophila counterpart. Furthermore, Hif-1 prolyl hydroxylase (Hph) is
      required for both complexes to drive growth. Our data suggest that the growth
      specific function of CycD/Cdk4 is conserved from arthropods to mammals.

PMID- 16582603
TI  - Common fragile sites nested at the interfaces of early and late-replicating
      chromosome bands: cis acting components of the G2/M checkpoint?
AB  - Common fragile sites (CFS) are evolutionary conserved loci where damage appears
      recurrently upon treatments perturbing DNA synthesis. Although long studied, the
      mechanisms underlying CFS fragility are still incompletely understood and CFS
      function is unknown. We have mapped most of them at the junction of chromosomal
      bands replicating at different times in S phase, indicating that specific
      replication programs take place at CFS. In good agreement with this finding, we
      obtained results suggesting that CFS remain incompletely replicated up to late
      G(2), even in cells that went unperturbed through S phase. The recent
      demonstration that the function of ATR and its downstream targets are crucial to
      CFS stability may thereby indicate that mitotic onset is delayed until completion
      of their replication. Altogether, available results now suggest that CFS
      constitute integral "cis" components of the G(2)-M checkpoint.

PMID- 16582604
TI  - Elimination of keratinocytes stagnant in s-phase through epidermal turnover
      instead of in situ apoptosis.

PMID- 16582605
TI  - BID as a double agent in cell life and death.
AB  - DNA damage leads to the activation of ATM and ATR, which in turn either cause
      cell cycle arrest and DNA repair or apoptosis. We have demonstrated that DNA
      damage leads to ATM-mediated BID phosphorylation, and that this phosphorylation
      regulates a novel, pro-survival function of BID important for S phase arrest.
      Thus, BID, a member from the core apoptotic regulatory machinery (BCL-2 family)
      receives direct inputs from a key regulator of the cell cycle arrest/DNA repair
      machinery (ATM), and therefore is an excellent candidate to coordinate genotoxic
      stress responses and apoptotic cell death.

PMID- 16582606
TI  - Phosphorylation of RIalpha by cyclin-dependent kinase CDK 2/cyclin E modulates
      the dissociation of the RIalpha-RFC40 complex.
AB  - We have previously demonstrated that the nuclear transport of the second subunit
      of the Replication Factor C complex, RFC40, by the regulatory subunit, RIalpha,
      of PKA is cell cycle specific and impairment in this transport results in G(1)
      arrest. In this study, we have investigated whether the cyclin-dependent kinases
      play a role in regulating the RIalpha-RFC40 complex formation. In this context,
      we have identified RIalpha as a novel substrate for the G(1)/S-Cyclin-dependent
      kinase, CDK2/Cyclin E, and found that RIalpha is specifically phosphorylated at
      the serine residue. Treatment of MCF7 cells with a CDK inhibitor, olomoucine,
      resulted in a significant accumulation in the RIalpha-RFC40 complex by 3.10 +/-
      0.08 fold and a parallel decrease in the RFC40-37 complex formation by 73.73 +/-
      11.81%. Furthermore, in vitro phosphorylation experiments suggest that,
      phosphorylation of RIalpha by CDK2/CyclinE kinase promotes the dissociation of
      the RIalpha-RFC40 complex and that once RIalpha is phosphorylated it cannot
      complex with RFC40. Inhibition of the serine-threonine phosphatase, PP1, by
      Calyculin A, significantly reduced the RIalpha-RFC40 complex formation,
      substantiating the in vitro phosphorylation data. Taken together, these findings
      suggest that CDK2/Cyclin E may function as downstream modulator that regulates
      the dissociation of the RIalpha-RFC40 complex and subsequently the association of
      the RFC40-RFC37 complex.

PMID- 16582607
TI  - Meisetz, a novel histone tri-methyltransferase, regulates meiosis-specific
      epigenesis.
AB  - Meiosis is a specialized cell division that is essential to reduce the ploidy of
      the genome and to generate genomic diversity in all sexually reproducing
      organisms. Our recent investigation revealed that the meiosis-specific histone
      methyltransferase Meisetz (Meiosis-induced factor containing PR/SET domain and
      zinc-finger motif) played an essential role on proper progression of meiotic
      prophase in mouse germ cell lineage. The finding also suggests that the germ cell
      lineage has a meiosis-specific epigenetic status that is different from that of
      the somatic cell lineage. This article reviews the function of Meisetz and
      prospects the epigenetic background allowing proper progression of meiosis in
      mouse germ cells.

PMID- 16582608
TI  - In vitro transformation models: modeling human cancer.
AB  - The development of cancer in humans involves a complex accumulation of genetic
      and epigenetic events mainly in proto-oncogenes and tumor-suppressor genes.
      Different combinations of these alterations have been observed in a given human
      cancer and an ever-increasing number of these genes seem to be involved in the
      distinct steps of neoplastic transformation. Nevertheless, recent successes in
      experimental models of immortalization and malignant transformation of human
      cells indicate that the disruption of a limited number of cellular pathways is
      sufficient to induce a cancerous phenotype in a wide variety of normal cells.
      This review summarizes in vitro transformation models recapitulating human
      carcinogenesis, which suggest that a series of genetic and cellular principles
      may govern the formation of most, if not all, types of human cancer.

PMID- 16582609
TI  - From mice to human: the "two-hit model" of leukemogenesis.

PMID- 16582611
TI  - The long and the short of it: linker histone H1 is required for metaphase
      chromosome compaction.
AB  - Faithful distribution of the genome to daughter cells requires that replicated
      chromatids are compacted and resolved from one another, and that functional
      kinetochores assemble at their centromeres to mediate spindle interactions. A
      molecular and mechanistic understanding of these critical processes is far from
      complete. We discovered that linker histone H1, a major chromatin component, is
      required for longitudinal compaction of replicated sperm chromosome arms in
      Xenopus laevis egg extracts that recapitulate the cell cycle in vitro. Due to
      their elongated structure, H1-depleted chromosomes could not be aligned or
      segregated by the spindle despite apparently normal kinetochore assembly.
      Interestingly, enrichment of H1 onto chromatin required passage through
      interphase, when DNA replication takes place. Here we show that interphase
      dependent loading is also a feature of kinetochore components including Ndc80.
      Thus, linker histone H1 contributes to chromosome condensation in vertebrates,
      and important molecular determinants of mitotic chromosome and kinetochore
      structure and function are established during interphase.

PMID- 16582610
TI  - Modeling liver cancer using zebrafish: a comparative oncogenomics approach.
AB  - Although the zebrafish has many attributes of a promising cancer model, one
      outstanding question is how similar zebrafish and human tumors are at the
      molecular level. To date, supporting data from histology and 'gene-to-gene'
      comparisons with human data offer limited insights. Using comparative microarray
      analyses, we found striking molecular similarities between zebrafish and human
      liver neoplasia. Our data indicate that zebrafish liver tumors possess the
      general molecular hallmarks of human liver cancer and some of the molecular
      similarities extend to the progression of liver tumors. The molecular
      conservation between fish and human liver tumors underscored the strong
      association and fundamental importance of these genes in liver neoplasia as well
      as their clinical potentials as diagnostic markers and/or therapeutic targets. In
      addition, our comparative oncogenomic work provides a general framework for
      comparing and validating microarray data of zebrafish model with human cancer,
      thus adding confidence of using the zebrafish to model human cancers.

PMID- 16582612
TI  - Dual regulation of the anaphase promoting complex in human cells by cyclin A-Cdk2
      and cyclin A-Cdk1 complexes.
AB  - In mammalian somatic cells, the Anaphase Promoting Complex (APC) is inactivated
      during S phase by active cyclin A-Cyclin dependent kinase (Cdk) 2 complexes
      promoting accumulation of mitotic regulators, such as cyclin B and Polo like
      kinase 1 (Plk1). However, mitotic entry does not appear to be perturbed in some
      human cancer cells or in normal mouse cells following Cdk2 RNA interference (i)
      or deletion of the Cdk2 gene. These results suggest functional complementation of
      APC regulation by a compensatory kinase. Using Plk1 protein level as readout of
      APC activity, we show that APC is inactivated during S phase in human cells by
      both cyclin A-Cdk2 and cyclin A-Cdk1 complexes. Expression of a dominant negative
      mutant of Cdk2 or Cdk2 RNAi in early S phase destabilizes Plk1 as it begins to
      accumulate. However, this effect wanes in late S phase, where destabilization of
      Plk1 also requires Cdk1 RNAi. Although Cdk2 is the dominant partner of cyclin A
      in these settings, cyclin A also binds Cdk1. Both complexes bind the APC
      targeting factor Cdh1, but Cdk1 complexes are inactive in early S phase,
      accounting for the stronger regulation of APC function by Cdk2. These results
      provide further evidence that cyclin A-Cdk2 and -Cdk1 complexes display
      overlapping and partially redundant roles in preparing cells for mitosis, through
      regulation of the APC.

PMID- 16582613
TI  - From kinases to cancer: leakiness, loss of autoinhibition and leukemia.
AB  - The class III receptor tyrosine kinase (RTK) "Fms-like tyrosine kinase 3" (FLT3)
      plays a key role in early hematopoesis. In acute myeloid leukemia (AML) two
      classes of activating FLT3 mutations are known: internal tandem duplications
      (FLT3-ITD) in the juxtamembrane domain and point mutations in the tyrosine kinase
      domain (FLT3-TKD). Recently, a third class of activating mutations was
      discovered, single point mutations in the juxtamembrane domain (FLT3-JM-PM).
      Since the crystal structure of the inactive conformation of FLT3 has recently
      been resolved the role of the juxtamembrane (JM) domain, serving as a key
      autoinhibitory element regulating kinase activity, was elucidated. Mutations in
      the JM domain seem to perturb the autoinhibitory activity of the JM domain
      thereby inducing autonomous activation of the kinase. These findings have
      important clinical implications. Routine screenings for mutations in FLT3 in
      leukemia diagnostics should also analyze point mutations in the JM domain of FLT3
      and patients harbouring FLT3-JM-PM might benefit from experimental therapeutic
      approaches with FLT3 inhibitors. The identification of FLT3-JM-PM is a remarkable
      example how single point mutations in the structurally important JM domain can
      turn RTKs into oncogenes.

PMID- 16582614
TI  - The human papillomavirus E7 protein shines a spotlight on the pRB family member,
      p130.

PMID- 16582615
TI  - Is the loss of pRb essential for the mouse skin carcinogenesis?
AB  - The pRb pathway is inactivated in most, if not all, human and mouse tumors,
      including skin tumors. However, a relatively low frequency of Rb gene alterations
      is found. The embryonic lethality of pRb-deficient animals restricts the analysis
      of these mice to midgestation and precludes the analysis of the roles of pRb in
      mouse cancer models. To solve this problem, we used the Cre/LoxP technology to
      induce the tissue-specific deletion of pRb. In epidermis, pRb deletion leads to
      altered proliferation and differentiation but these alterations do not induce the
      development of spontaneous skin tumors. To gain insight in the possible roles of
      pRb in mouse skin carcinogenesis, we have performed chemical tumorigenesis
      experiments in mice bearing epidermal-specific inactivation of Rb gene.
      Unexpectedly, these mice develop fewer and smaller tumors than control animals,
      but showing increased malignant conversion to squamous cell carcinomas. Detailed
      biochemical analysis demonstrates that, in the absence of pRb, multiple pathways
      are activated leading to increased tumor apoptosis. In particular, we
      characterized the aberrant p53 activation mediated by E2F/p19(ARF) and other
      transduction pathways. This may generate a selective pressure in the tumor
      leading to premature p53 loss of function, which ultimately results in increased
      malignancy. Overall, these data highlights the role of pRb during the malignant
      conversion in the mouse skin carcinogenesis, and the intimate relationships
      between pRb and multiple tumor suppressor networks in this system.

PMID- 16582616
TI  - Epigenetics and cancer: altered chromatin remodeling via Snf5 loss leads to
      aberrant cell cycle regulation.
AB  - The term 'epigenetics' refers to heritable changes in gene function that occur in
      the absence of any change in DNA sequence. Perturbations of epigenetic gene
      regulation may play a critical role in the genesis of most, if not all, cancers.
      These alterations include changes in covalent modifications of DNA and histones
      as well as non covalent changes in nucleosome positioning. Covalent epigenetic
      modifications have been the main focus of cancer investigation, perhaps because
      they are more readily assayed and understood than non covalent modifications.
      Recently, evidence has emerged demonstrating that perturbation of complexes that
      remodel the structure of chromatin by mobilizing nucleosomes may have a key role
      in tumor suppression and oncogenic transformation. For example, Snf5
      (Ini1/Baf47/Smarcb1), a core component of the Swi/Snf ATPase chromatin remodeling
      complex, is a potent tumor suppressor that is specifically inactivated in lethal
      childhood cancers. Notably, these cancers may serve as a paradigm for epigenetic
      cancers as, despite their extremely aggressive nature, the majority have an
      entirely normal karyotype with only microdeletions at the Snf5 locus. Recent
      investigations have shed light upon the mechanistic basis of Snf5 function by
      demonstrating that Snf5 and the Swi/Snf complex regulate the cell cycle and
      cooperate with p53 to prevent oncogenic transformation.

PMID- 16582617
TI  - Counting divisions in a human somatic cell tree: how, what and why?
AB  - The billions of cells within an individual can be organized by genealogy into a
      single somatic cell tree that starts from the zygote and ends with present day
      cells. In theory, this tree can be reconstructed from replication errors that
      surreptitiously record divisions and ancestry. Such a molecular clock approach is
      currently impractical because somatic mutations are rare, but more feasible
      measurements are possible by substituting instead the 5' to 3' order of
      epigenetic modifications such as CpG methylation. Epigenetic somatic errors are
      readily detected as age-related changes in methylation, which suggests certain
      adult stem cells divide frequently and "compete" for survival within niches.
      Potentially the genealogy of any human cell may be reconstructed without prior
      experimental manipulation by merely reading histories recorded in their genomes.

PMID- 16582618
TI  - p19INK4D and cell death.
AB  - INK4 proteins are members of a family of cyclin-dependent kinase (CDK) inhibitors
      that function in G(1) to block the activity of CDKs 4 and 6. While they share
      clear structural similarities, numerous studies have shown that INK4 proteins
      differ in their expression patterns during development and in the adult, and have
      differing roles in tumor suppression. A recent study from our laboratory showed
      that expression of the gene encoding p19(INK4D) is induced by the hormonal form
      of vitamin D(3) and by retinoids, both of which signal through related nuclear
      receptor transcription factors. Although vitamin D(3) and retinoids have distinct
      developmental and physiological functions, both regulate the cell cycle and have
      been shown to have chemopreventive effects in a range of studies. Induction of
      p19(INK4D) expression contributed to cell cycle arrest by both ligands. However,
      knockdown of p19(INK4D) rendered cells sensitive to autophagic cell death, a
      remarkable phenotype given the hyperproliferative responses to loss of other INK4
      proteins. We discuss the relevance of our studies and recent findings of others
      to the cell death observed in p19(INK4D)-deficient animals and to a possible role
      for p19(INK4D) induction in chemoprevention.

PMID- 16582619
TI  - Identification of novel ARF binding proteins by two-hybrid screening.
AB  - The ARF tumor suppressor protects us against cancer through protein-protein
      interactions in partially defined p53-dependent and p53-independent pathways. We
      performed a two-hybrid screen using ARF as bait and present the identification of
      several new ARF partners that may regulate its growth inhibitory signaling. The
      potential physiological roles of these novel ARF binding proteins in regulating
      ARF signaling are discussed.

PMID- 16582620
TI  - Negative feedbacks in normal cell growth and their suppression in tumorigenesis.

PMID- 16582621
TI  - Differential subcellular localizations of two human Sgo1 isoforms: implications
      in regulation of sister chromatid cohesion and microtubule dynamics.
AB  - Sgo1 is an evolutionarily conserved protein that functions as a protector of
      centromeric cohesin during mitosis. Recent studies show that Sgo1 is
      kinetochorelocalized and required for accurate segregation of mitotic chromosomes
      because depletion of Sgo1 in mammalian cells results in precocious initiation of
      anaphase and mis-segregation of chromosomes. Through analysis of GFP fusion
      proteins, we observe that two major isoforms of human Sgo1 exhibit entirely
      different subcellular localization patterns. The short isoform of Sgo1 (sSgo1)
      that lacks exon 6 does not localize to kinetochores during any stages of the cell
      cycle. Instead, it is enriched at mitotic spindles. On the other hand, the longer
      isoform of Sgo1 primarily localizes to kinetochores during G(2) phase and mitotic
      prophase, metaphase, and anaphase. During late mitosis, Sgo1 does not appear to
      be associated with kinetochores. Intriguingly, the longer isoform of Sgo1 forms
      discrete foci during S phase, some of which are apparently in the nucleoli.
      However, a majority of these foci colocalize with CREST, a kinetochore antigen,
      indicating that Sgo1 is loaded onto kinetochores during or immediately after DNA
      replication. Together, our studies suggest that different isoforms of Sgo1 may
      play distinct roles during the cell cycle and that Sgo1 may have an interphase
      function as well.

PMID- 16582622
TI  - Akt/PKB signaling in cancer: a function in cell motility and invasion.
AB  - The PI 3-K signaling pathway has been the subject of intense investigation for
      over a decade because it regulates a multitude of cellular processes.
      Deregulation of this pathway often results in human diseases such as cancer. The
      serine/threonine kinase Akt, a major PI 3-K target in all cells, has received
      considerable attention because it provides tumor cells with enhanced survival
      capacity. Many tumors and tumor cells display elevated Akt protein expression and
      activity, and many of the proteins which regulate Akt itself are also often
      mutated in cancer. For this reason, Akt has become a viable drug target for
      cancer therapy. However, recent studies have shown that Akt can also function as
      a suppressor of tumor cell migration and invasion, phenotypes which are directly
      linked to metastatic tumor progression. Here we review these findings and
      consider the unexpected notion that Akt may function as a metastasis suppressor.

PMID- 16582623
TI  - Adult neurogenesis: basic concepts of signaling.
AB  - Findings over the past decades demonstrating persistent neurogenesis in the adult
      brain have challenged the view of a fixed circuitry in normally functioning brain
      and raised hopes for self-renewal following brain injury. In addition to
      providing insights for repair, studying adult neurogenesis may improve our
      understanding of embryonic development assuming that fundamental mechanisms are
      similar. It is argued here, using examples of cell:cell communication, that
      parallels can be drawn between adult and embryonic neurogenesis. Paradoxically,
      cell:cell communication in neurogenic regions resembles that in a mature
      neuroglial network. This suggests that differences in the integrative properties
      of cells and the extracellular matrix molecules may constitute a neurogenic
      environment or "niche". While reasons for persistent adult neurogenesis in humans
      remains obscure, recent findings regarding the environmental and activity-driven
      control of neurogenesis reinforce the original concept of a role for neurogenesis
      in motor memory formation and refinement of information processing.

PMID- 16582624
TI  - Localization of the translational guanine nucleotide exchange factor eIF2B: a
      common theme for GEFs?
AB  - The eukaryotic initiation factor 2B (eIF2B) serves an essential recycling
      function in protein synthesis. As the guanine nucleotide exchange factor for
      eIF2, it recycles eIF2 from a GDP to a GTP bound form that is competent for
      translation initiation. Stress-dependent controls target this eIF2B-recycling
      step allowing a reprogramming of the global gene expression profile. In addition,
      a human disease, leukoencephalopathy with vanishing white matter (VWM), is caused
      by mutations in the eIF2B subunit genes. Recently, we have found that the eIF2B
      guanine nucleotide exchange factor resides in a specific cytoplasmic focus in the
      yeast, Saccharmoyces cerevisiae. eIF2B is a resident feature of this focus,
      whereas eIF2 shuttles to and fro. Moreover, the in vivo rate of eIF2 shuttling
      correlates with changes in guanine nucleotide exchange activity implicating this
      large cytoplasmic focus as a site of guanine nucleotide exchange. In this
      perspective, we discuss these findings in the wider context of the assortment of
      guanine nucleotide exchange factors.

PMID- 16582625
TI  - The fatty acid synthase gene is a conserved p53 family target from worm to human.
AB  - The discovery that the p53 family consists of three members (p53, p63 and p73) in
      vertebrates and of a single homolog in invertebrates has raised the challenge of
      understanding the functions of the ancestor and how they have evolved and
      differentiated within the duplicated genes in vertebrates. Here, we report that
      the fatty acid synthase (FAS) gene, encoding for a key enzyme involved in the
      biogenesis of membrane lipids in rapidly proliferating cells, is a conserved
      target of the p53 family throughout the evolution. We show that CEP-1, the C.
      elegans p53 homolog, is able to bind the two p53 family responsive elements (REs)
      identified in the worm fasn-1 gene. Moreover, we demonstrate that fasn-1
      expression is modulated by CEP-1 in vivo, by comparing wild-type and CEP-1
      knockout worms. In human, luciferase and chromatin immunoprecipitation assays
      demonstrate that TAp73alpha and DeltaNp63alpha, but not p53, TAp73beta and
      TAp63alpha bind the two p53 REs of the human FASN gene. We show that the ectopic
      expression of TAp73alpha and DeltaNp63alpha leads to an increase of FASN mRNA
      levels, while their silencing produces a decrease of FASN expression.
      Furthermore, we present data showing a correlation between DeltaNp63alpha and
      FASN expression in cellular proliferation. Of relevant importance is that fasn-1
      is the first CEP-1 direct target gene identified so far in C. elegans and our
      results suggest a new CEP-1 role in cellular proliferation and development,
      besides the one already described in apoptosis of germ cells. These data confirm
      the hypothesis that the ancestral functions of the single invertebrate gene may
      have been spread out among the three vertebrate members, each of them have
      acquired specific role in cell cycle regulation.

PMID- 16582627
TI  - Brave little world: spheroids as an in vitro model to study tumor-immune-cell
      interactions.
AB  - Multicellular tumor spheroids (MCTS) are a well-established 3-D in vitro model
      system that reflects the pathophysiological in vivo situation in tumor
      microregions and of avascular micrometastatic sites. Because monocytes and other
      immune cells infiltrate into MCTS of different origin, such spheroid cocultures
      are a valuable, still underestimated tool to systematically study heterologous
      interactions between tumor and immune cells. The present article gives a brief
      overview on work that has been published on tumor-immune cell interactions in
      MCTS and also summarizes mechanisms of immune suppression in the tumor milieu
      focussing on myeloid cells. Using the coculture model, we recently demonstrated
      that tumor-derived lactic acid is a potent modulator of human monocyte as lactic
      acid inhibited the differentiation of monocytes (MO) into dendritic cells (DC)
      and also impaired antigen presentation. We show herein, that the capacity of
      various tumor cells in MCTS to secrete lactic acid differs up to tenfold,
      suggesting that this capacity is dependent on the tumor cell type. It is further
      demonstrated that lactic acid disturbs the migration of MO into MCTS as
      infiltration could be increased by blocking lactic acid production. We therefore
      discuss lactic acid which accumulates in many tumors and tumor microregions as a
      potent immune suppressor for MO/DC in the tumor milieu and conclude that these
      data are highly relevant for adoptive immunotherapy protocols with DC.

PMID- 16582626
TI  - p14ARF triggers G2 arrest through ERK-mediated Cdc25C phosphorylation,
      ubiquitination and proteasomal degradation.
AB  - The Cdc25C phosphatase is a key regulator of mitotic entry which activity is
      tightly regulated by phosphorylation. In response to DNA damage, phosphorylation
      at serine 216 induces the cytosolic retention of Cdc25C through 14-3-3 binding.
      We previously reported the ability of the p14ARF tumor suppressor to induce the
      accumulation of inactive phospho-Cdc25C(Ser216) protein as well as a decrease of
      Cdc25C steady state level and correlated these events with a p53-independent G2
      arrest. The aim of this study was to investigate the cellular signaling pathways
      involved in this process. By using specific pharmacological inhibitors, we
      demonstrate that activation of the ERK1/2 MAP kinases pathway is involved in the
      p53-independent G2 checkpoint induced by p14ARF Moreover, we show that activated
      P-ERK1/2 bind and phosphorylate Cdc25C on its ser216 residue following p14ARF
      expression, thereby identifying Cdc25C as a new ERK1/2 target. Importantly, we
      further show that phosphorylation at Ser216 by phospho-ERK1/2 promotes Cdc25C
      ubiquitination and proteasomal degradation, suggesting that Cdc25C proteolysis is
      required for a sustained G2 arrest in response to p14ARF. Taken together, these
      results demonstrate that the MAPK ERK signaling pathway contributes to the p53
      independent antiproliferative functions of p14ARF. Furthermore, they identify a
      new mechanism by which phosphorylation at serine 216 participates to Cdc25C
      inactivation.

PMID- 16582628
TI  - DNA damage signaling and repair in Dictyostelium discoideum.
AB  - Repair of DNA double strand breaks (DSBs) is critical for the maintenance of
      genome integrity. DNA DSBs can be repaired by either homologous recombination
      (HR) or nonhomologous end-joining (NHEJ). Whilst HR requires sequences homologous
      to the damaged DNA template in order to facilitate repair, NHEJ occurs through
      recognition of DNA DSBs by a variety of proteins that process and rejoin DNA
      termini by direct ligation. Here we review two recent reports that NHEJ is
      conserved in the social amoeba Dictyostelium discoideum. Certain components of
      the mammalian NHEJ pathway that are absent in genetically tractable organisms
      such as yeast are present in Dictyostelium and we discuss potential directions
      for future research, in addition to considering this organism as a genetic model
      system for the study of NHEJ in vivo.

PMID- 16582629
TI  - In vivo analysis of Drosophila deoxyribonucleoside kinase function in cell cycle,
      cell survival and anti-cancer drugs resistance.
AB  - In vitro studies have shown that Drosophila melanogaster has a highly efficient
      single deoxyribonucleoside kinase (dNK) multisubstrate enzyme. dNK is related to
      the mammalian Thymidine Kinase 2 (TK2) group involved in the nucleotide synthesis
      salvage pathway. To study the dNK function in vivo, we constructed transgenic
      Drosophila strains and impaired the nucleotide de novo synthesis pathway, using
      antifolates such as aminopterin. Our results show that dNK overexpression rescues
      both cell death and cell cycle arrest triggered by this anti-cancer drug, and
      confers global resistance on the fly. Moreover, we show that fly viability and
      growth depend on the exquisite ratio between dNK expression and its substrate
      thymidine (dT) in the medium, and that increased dT concentrations trigger
      apoptosis and a decrease in body mass when dNK is mis-expressed. Finally, dNK
      expression, unlike that of TK2, is cell cycle dependent and under the control of
      CyclinE and the dE2F1 transcription factor involved in the G1/S transition. dNK
      is therefore functionally more closely related to mammalian TK1 than to TK2. This
      strongly suggests that dNK plays a role in cell proliferation in physiological
      conditions.

PMID- 16582630
TI  - Shedding light on mammary stem cells and tumorigenesis.

PMID- 16582631
TI  - Epigenetic information in chromatin: the code of entry for DNA repair.
AB  - Epigenetic changes are important etiological factors of human cancer. Epigenetic
      information in chromatin (known as 'histone code') is a fascinating feature used
      by cells to extend and modulate the genetic (DNA) code. The histone code is thus
      proposed to be 'read' by cells to regulate accessibility to, and functions of,
      chromatin DNA. While the role of the epigenetic code involving chromatin
      modifying/remodeling complexes in transcriptional regulation is well established,
      it is only recently that these mechanisms have been implicated in DNA damage
      detection and DNA repair. However, how the components of the DNA damage sensing
      and repair machinery gain access to broken DNA in compacted chromatin remains a
      mystery. Recent studies provide important insights into DNA damage- and repair
      specific modifications to histones and shed light on how the epigenetic code
      controls DNA repair.

PMID- 16582632
TI  - Tumor suppression by p53 without accelerated aging: just enough of a good thing?
AB  - The prevalence of mutations that inactivate the p53 tumor suppressor gene in
      human cancers reveals the importance of p53 in preventing cancer. Recent progress
      has generated increased enthusiasm for re-activating p53 in tumors with mutant
      p53 proteins as well as for increasing p53 function in tumors expressing wild
      type p53 that is inhibited in trans. However, excessive p53 activity can be
      detrimental to the host, potentially limiting the utility of p53 activation as a
      therapeutic strategy. For example, uncontrolled p53 activity is lethal to the
      murine embryo, and p53 has been associated with increased aging in people and
      mice. Here we review the literature linking p53 to aging and discuss reports
      demonstrating that p53 can suppress tumor formation without accelerating aging.
      We raise the possibility that activation of p53 remains a promising strategy for
      cancer chemoprevention and therapy even if, under some circumstances, p53 might
      accelerate aging.

PMID- 16582633
TI  - Loss of PU.1: one of the many roads to myeloid leukemia.

PMID- 16582635
TI  - Role of the TRF2 telomeric protein in cancer and ageing.
AB  - Telomeres are the special heterochromatin that forms the ends of chromosomes,
      consisting of TTAGGG repeats and associated proteins. Telomeres protect the ends
      from degradation and recombination, and are essential for chromosomal stability.
      Both a minimal length of telomere repeats and the telomere-binding proteins are
      required for telomere protection. Telomerase is a DNA polymerase that
      specifically elongates telomeres, in this way regulating telomere length and
      function. A minimal telomere length is required to maintain tissue homeostasis.
      On one hand, critically short telomeres trigger loss of cell viability and
      premature death in mice deficient for telomerase activity. Furthermore, altered
      functioning of telomerase and telomere-interacting proteins is present in some
      human premature ageing syndromes and cancer. A new mouse model with critically
      short telomeres has been generated by overexpressing the TRF2 telomere-binding
      protein, K5-TRF2 mice. These mice show short telomeres in the presence of
      telomerase activity, leading to premature aging and increased cancer. Short
      telomeres in TRF2 mice can be rescued in the absence of the XPF nuclease,
      indicating that this enzyme rapidly degrades telomeres in the presence of
      increased TRF2 expression. K5-TRF2 mice represent a new tool to understand the
      consequences of critical telomere shortening a telomerase-proficient genetic
      background, more closely resembling human cancer and aging pathologies.

PMID- 16582634
TI  - Genomic profiling identifies discrete deletions associated with translocations in
      glioblastoma multiforme.
AB  - Glioblastoma multiforme is the most common tumor arising in the central nervous
      system. Patients with these tumors have limited treatment options and their
      disease is invariably fatal. Molecularly targeted agents offer the potential to
      improve patient treatment, however the use of these will require a fuller
      understanding of the genetic changes in these complex tumors. In this study, we
      identify copy number changes in a series of glioblastoma multiforme tumors and
      cell lines by applying high-resolution microarray comparative genomic
      hybridization. Molecular cytogenetic characterization of the cell lines revealed
      that copy number changes define translocation breakpoints. We focused on
      chromosome 6 and further characterized three regions of copy number change
      associated with translocations including a discrete deletion involving IGF2R,
      PARK2, PACRG and QKI and an unbalanced translocation involving POLH, GTPBP2 and
      PTPRZ1.

PMID- 16582636
TI  - The dual specificity phosphatase Cdc25C is a direct target for transcriptional
      repression by the tumor suppressor p53.
AB  - The cdc25C gene has been shown to be a novel target for transcriptional
      downregulation by p53. Two independent mechanisms contribute to the p53-dependent
      repression of the cdc25C gene. First, an element in the cdc25C promoter
      consisting of a binding site for p53 plus an adjacent 8 base pairs confers p53
      dependent repression. Mutation of either the p53 binding site or the adjacent 8
      bp sequence abolishes this effect. The element conferring p53-dependent
      repression also contains a binding site for the transcription factor Sp1 and a
      mutant p53 protein that retains the ability to interact with the p53-binding site
      is defective in mediating repression. Second, a minimal promoter lacking the p53
      binding site but containing a previously characterized CDE/CHR element is also
      repressed by p53. This repression is abrogated when a 5 bp mutation is introduced
      in the CHR sequence. These results support a model for p53 downregulating cdc25C
      expression, in part, by direct binding to a promoter element that is likely to
      require cooperation with an additional cellular factor.

PMID- 16582637
TI  - Regulation of rRNA synthesis in human and mouse cells is not determined by
      changes in active gene count.
AB  - Growth regulation of the tandemly repeated ribosomal RNA (rRNA) genes in mammals
      can potentially occur by several distinct mechanisms. Only a fraction of the 200
      or so rRNA genes appears to be activated in somatic cells, leaving open the
      possibility that enhanced transcription could result from gene activation events.
      Here we have determined the active rRNA gene count after growth stimulation with
      EGF, direct Raf activation and chromatin hyperacetylation and after inhibiting
      MAP-kinase signaling. Despite robust changes in rRNA transcription rates, we find
      no significant variation in active gene number in either mouse fibroblasts or
      human neuroepithelioma cells. Interestingly, the data also show that rRNA
      transcription enhancement induced by hyperacetylation is dependent on MEK/ERK
      signaling. Since ERK and the acetyltransferase CBP both bind the architectural
      factor UBF, this suggests a mechanism for targeting active CBP to the rRNA genes.

PMID- 16582638
TI  - Halting neuroblastoma metastasis by controlling integrin-mediated death.
AB  - Neuroblastoma, a common tumor of nervous system origin in young children, is
      usually detected only after the primary tumor has metastasized and the chances of
      its complete removal are low. Metastatic neuroblastoma cells commonly suppress
      expression of the gene encoding caspase-8. In a neuroblastoma murine model,
      expression of caspase-8 and integrin alpha3beta1 was dramatically reduced during
      tumor development. Analysis of clinical biopsies supported the observation that
      expression of both genes is low in human patients with metastatic disease. These
      data suggest that loss of expression of both caspase-8 and unligated integrins
      contribute to the survival of tumor cells migrating from the primary tumor.
      Integrin receptors that are unable to find appropriate ligands can form a large
      molecular complex containing caspase-8, explaining why cells that have diminished
      expression of either of these two genes have a significant survival advantage in
      foreign microenvironments. Thus, upregulating expression of caspase-8 and
      integrins, or alternatively, antagonizing integrins within the primary tumor may
      be important therapeutically in halting neuroblastoma metastasis.

PMID- 16582639
TI  - Histone deacetylation is required for orderly meiosis.
AB  - Histone acetylation is associated with a diversity of chromatin-related processes
      in mitosis. However, its roles in mammalian oocyte meiosis are largely unknown.
      In the present study, we first investigated in detail the acetylation changes
      during porcine oocyte maturation using a panel of antibodies specific for the
      critical acetylated forms of histone H3 and H4, and showed meiosis stage
      dependent and lysine residue-specific patterns of histone acetylation. By using
      trichostatin A (TSA), a general inhibitor of histone deacetylases (HDACs), we
      further determined that selective inhibition of histone deacetylation (thereby
      maintaining hyperacetylation) delayed the onset of germinal vesicle breakdown and
      produced a high frequency of lagging chromosomes or chromatin bridges at anaphase
      and telophase I (AT-I), suggesting that histone deacetylation is required for
      orderly meiotic resumption and accurate chromosome segregation in porcine
      oocytes. In addition, we examined the localization and expression of HDAC1 by
      performing immunofluorescence and immunoblotting analysis. The results showed
      that subcellular translocation, expression level and phosphorylated modification
      of HDAC1 were temporally regulated and likely to coparticipate in the
      establishment of histone acetylation profiles in oocyte meiosis.

PMID- 16582640
TI  - Surgical management of posterior fossa arteriovenous malformations.
AB  - OBJECTIVE: Arteriovenous malformations (AVMs) involving the cerebellum and
      brainstem are relatively rare lesions that most often present clinically as a
      result of a hemorrhagic episode. Although these AVMs were once thought to have a
      more aggressive clinical course in comparison with supratentorial AVMs, recent
      autopsy data suggests that there may be little difference in hemorrhage rates
      between the two locations. Although current management of these lesions often
      involves preoperative embolization and stereotactic radiosurgery, surgical
      resection remains the treatment of choice, conferring immediate protection to the
      patient from the risk of future hemorrhage. METHODS: Most symptomatic AVMs that
      involve the cerebellum and the pial or ependymal surfaces of the brainstem are
      candidates for surgical resection. Preoperative angiography and magnetic
      resonance imaging studies are critical to determine suitability for resection and
      choice of operative exposure. In addition to considering the location of the
      nidus, arterial supply, and predominant venous drainage, the surgical approach
      must also be selected with consideration of the small confines of the posterior
      fossa and eloquence of the brainstem, cranial nerves, and deep cerebellar nuclei.
      RESULTS: Since the 1980s, progressive advances in preoperative embolization,
      frameless stereotaxy, and intraoperative electrophysiologic monitoring have
      significantly improved the number of posterior fossa AVMs amenable to
      microsurgical resection with minimal morbidity and mortality. CONCLUSION: Future
      improvements in endovascular technology and stereotactic radiosurgery will likely
      continue to increase the number of posterior fossa AVMs that can safely be
      removed and further improve the clinical outcomes associated with microsurgical
      resection.

PMID- 16582641
TI  - Quantification and comparison of telovelar and transvermian approaches to the
      fourth ventricle.
AB  - OBJECTIVE: To quantify the exposure to the fourth ventricle obtained with the
      telovelar and transvermian approaches. METHODS: The telovelar, with and without
      C1 posterior arch removal, and transvermian approaches were performed on six
      cadaveric heads. The area of surgical exposure was calculated from triangles
      formed by defined anatomic points. A robotic microscope was used to determine the
      "angle of approach" for the same points. RESULTS: The maximal allowable vertical
      angle of attack to the obex of the fourth ventricle was significantly greater
      with the telovelar approach than with the transvermian approach (P < 0.002), but
      there was no difference at the rostral fourth ventricle. The maximal allowable
      horizontal angle of attack at the level of the obex, Luschka, and rostral fourth
      ventricle was significantly greater with the telovelar than with the transvermian
      approach (P < 0.001). Removal of the C1 posterior arch with the telovelar
      approach significantly increased the vertical angle of approach to the obex (P <
      0.001) and rostral aspect of the fourth ventricle (P = 0.005) compared with the
      telovelar alone. The telovelar approach with C1 arch removal offered a larger
      working area than the transvermian approach (P < 0.001). CONCLUSION: Except for
      the vertical angle to the rostral aspect of the fourth ventricle, the telovelar
      approach provides greater angle of exposure in all planes than the transvermian
      approach. Removal of the C1 posterior arch obviates this sole advantage of the
      transvermian approach. The telovelar approach offers a corridor through
      noneloquent arachnoid planes and a safe and capacious working environment.

PMID- 16582642
TI  - The extended retrosigmoid approach: an alternative to radical cranial base
      approaches for posterior fossa lesions.
AB  - OBJECTIVE: The extended retrosigmoid approach is presented as a simple and safe
      modification of the traditional retrosigmoid approach, with increased exposure
      resulting from a limited mastoidectomy and skeletonization of the sigmoid sinus.
      METHODS: Patients with posterior fossa vascular lesions treated with the extended
      retrosigmoid approach between 1997 and 2003 were reviewed. A detailed description
      of the surgical approach, as well as case illustrations, is provided. We present
      a video narrated by the senior author in which a description of the technique is
      offered. RESULTS: Thirty-eight patients underwent this approach to manage 40
      lesions, including 15 dural arteriovenous fistulae, 9 arteriovenous
      malformations, 10 cavernous malformations, and 6 aneurysms. The extended
      retrosigmoid approach differs from the traditional approach with its C-shaped
      skin incision, posterior mastoidectomy, and extensive dissection of the sigmoid
      sinus, craniotomy rather than craniectomy, and anterior mobilization of the sinus
      with the dural flap. CONCLUSION: The application of the extended retrosigmoid
      approach to a series of complex lesions in the posterior fossa demonstrates its
      applicability as an alternative to radical cranial base approaches. The extended
      retrosigmoid approach requires a fundamental change in the management of the
      sigmoid sinus. The neurosurgeon must be familiar with petrous bone anatomy,
      experienced dissecting through bone using a high-speed drill, and comfortable
      working directly over a major venous sinus. The technical modifications of the
      extended retrosigmoid approach can be incorporated into the neurosurgical
      repertoire and will enhance exposure of the cerebellopontine angle and deep
      vascular structures, thereby minimizing the need for brain retraction and other
      transpetrous approaches.

PMID- 16582643
TI  - Anterolateral approach to the V1 segment of the vertebral artery.
AB  - OBJECTIVE: We describe the normal anatomy, variations, and the surgical technique
      to expose and control the V1 segment of the vertebral artery (VA). METHODS: The
      VA V1 segment extends classically from the subclavian artery to the C6 transverse
      foramen. It courses obliquely upwards and posteriorly in the cervical fat tissue,
      at a distance of 5 to 10 mm from the C7 vertebral body. Along its course, the VA
      V1 segment is crossed by the inferior thyroid artery, the thoracic duct, and the
      sympathetic chain. For neurosurgeons, the safest approach is to expose the distal
      part of the V1 segment at the C6 transverse foramen level through an antero
      lateral approach. Otherwise, direct exposure of the subclavian artery requires
      vascular surgery expertise. RESULTS: Surgical exposure of the VA V1 segment can
      be indicated on approaching the C6-C7 intervertebral disc space for degenerative
      disease or on treating tumoral processes in its vicinity. With developments of
      endovascular techniques, revascularization procedures are more rarely indicated
      nowadays. CONCLUSION: Perfect knowledge of the anatomy and of the surgical
      technique permits a safe exposure and control of the VA V1 segment.

PMID- 16582644
TI  - Microsurgical anatomy of the oculomotor cistern.
AB  - OBJECTIVE: To define the characteristics of the arachnoidal sleeve and cistern
      that accompany the oculomotor nerve through the cavernous sinus roof. METHODS:
      Forty cavernous sinuses were examined using 3 to 40x magnification. Information
      was obtained about the size of the oculomotor cistern and its relationship to the
      roof of the cavernous sinus and anterior clinoid process. RESULTS: An arachnoidal
      sleeve and cistern, referred to as the oculomotor cistern, accompanied the
      oculomotor nerve into the roof of all the cavernous sinuses examined. The
      oculomotor cistern extends from the oculomotor porus, where the nerve enters the
      roof of the cavernous sinus, to the area below the tip or the adjacent part of
      the lower margin of the anterior clinoid process. From the porus, the nerve
      passes forward and downward to the depth of the cistern where it becomes
      incorporated into the fibrous lateral wall of the cavernous sinus. The width of
      the cistern was maximal at the oculomotor porus averaged 5.5 mm (range, 3.0-9.2
      mm), and tapered slightly towards the midpoint and deep end of the cistern. The
      cistern's average length was 6.5 mm (range, 3.0-11.0 mm). The oculomotor nerve
      usually coursed closer to the anterior than the posterior wall of the cistern at
      the level of the oculomotor porus. CONCLUSION: The oculomotor cistern, an
      arachnoidal and dural cuff, accompanies the oculomotor nerve through the
      cavernous sinus roof to the area just below or anterior to the lower edge of the
      tip of the anterior clinoid process. The segment of the nerve inside the
      oculomotor cistern is interposed between its free portion in the interpeduncular
      cistern and the part of its course where it is incorporated into the fibrous
      lateral wall of the cavernous sinus. The cistern can be opened to aid in the
      exposure and mobilization of the nerve in dealing with pathology in the area.

PMID- 16582645
TI  - One-piece versus two-piece orbitozygomatic craniotomy: quantitative and
      qualitative considerations.
AB  - OBJECTIVE: The orbitozygomatic (OZ) craniotomy minimizes brain retraction and
      improves cranial base exposure by providing a multidirectional view, increased
      operative angles and working space. The two main variations of the approach
      include the one-piece and the two-piece types. The microsurgical anatomy of the
      one- and two-piece OZ craniotomies are presented with the goal of comparing the
      extent of orbital roof removal between these two craniotomies and the effect of
      orbital roof removal on operative exposure. METHODS: Ten two-piece and 11 one
      piece OZ craniotomies were performed in a stepwise manner simulating the
      approaches on formalin fixed specimens. The orbital surface area removed above
      the frontozygomatic suture extending medially over the orbital roof was measured
      from each bone flap. The two-sided unpaired t test using STATA 7.0 software was
      used to compare the amount of orbital roof removed using the two approaches.
      RESULTS: The two-piece OZ craniotomy allowed for the removal of a larger portion
      of the roof and lateral wall of the orbit than the one-piece. The total
      orbitotomy, including the orbital roof plus the part of the lateral wall above
      the frontozygomatic suture, had an average surface area of 996 +/- 229 mm for the
      two piece and 372 +/- 103 mm for the one-piece. The orbital roof made up 27 +/-
      18% of the orbital osteotomy for the one-piece craniotomies and 67 +/- 10% of the
      osteotomy for the two-piece craniotomies (P < 0.001). CONCLUSION: The two-piece
      OZ craniotomy allows for more extensive orbital roof removal and better
      visualization of the basal frontal lobe. Therefore, the two-piece may result in a
      lower incidence of enophtalmus and poor cosmetic outcomes, particularly if the
      remaining orbital roof must be removed piecemeal during the one-piece OZ
      craniotomy in order to obtain satisfactory exposure.

PMID- 16582646
TI  - Surgical anatomy of dural defects in spontaneous spinal cerebrospinal fluid
      leaks.
AB  - OBJECTIVE: Spontaneous intracranial hypotension is typically caused by a
      spontaneous spinal cerebrospinal fluid (CSF) leak. The configuration of the
      related dural defects can be complex. We describe our experience with the
      surgical anatomy of these defects. METHODS: Thirteen consecutive patients with
      spontaneous spinal CSF leaks who underwent surgical exploration at Mayo Clinic
      between 1994 and 2003 were studied. All patients' records, imaging studies,
      detailed intraoperative findings, and outcomes were reviewed. RESULTS: There were
      four men and nine women with an average age of 40 years (range, 12-62 yr).
      Preoperative imaging studies revealed a single site of CSF leak in eight
      patients, two sites in three patients, and multiple sites in two patients.
      Intraoperatively, the exact site of leakage could not be found in four patients.
      Among the other nine patients, primary closure of a meningeal diverticulum was
      achieved in one patient. Significant regional attenuation of the dura prevented
      primary repair of the leak site in eight patients. Muscle, fibrin glue, and
      Gelfoam (Upjohn Co., Kalamazoo, MI) soaked in patient's own blood were commonly
      used to pack the epidural space in an attempt to seal the site of the leak.
      Ligation of two nonappendicular nerve roots allowed closure of the leak in one of
      these patients. Postoperatively, resolution of symptoms occurred in eight
      patients, significant improvement was noted in three patients, and only transient
      resolution in two. The mean duration of follow-up was 20.5 months. CONCLUSION:
      Surgery for closure of spontaneous spinal CSF leaks may not be straightforward.
      Even when extradural CSF leakage is discovered preoperatively by imaging studies,
      it may not always be possible to identify the exact site of the leakage
      intraoperatively. Furthermore, the anatomy of the dural defects may be complex
      and not amenable to primary closure. In such cases, the use of adjuvant
      techniques during surgical exploration may be effective.

PMID- 16582648
TI  - Intra/extra-aneurysmal stent placement for management of complex and wide-necked-
      bifurcation aneurysms: eight cases using the waffle cone technique.
AB  - OBJECTIVE: To describe a novel application of the Neuroform stent (Boston
      Scientific-Target, Fremont, CA) for the management of eight wide-necked
      aneurysms. METHODS: All patients were treated using a single Neuroform stent
      placed partially into the aneurysm and into the afferent artery. The portion of
      the stent protruding into the aneurysm fundus provided neck support for the
      subsequent successful coiling. CONCLUSION: The Neuroform stent is a versatile
      device that can be used in a variety of ways to assist in the coiling of wide
      necked aneurysms. The technique described here may be used for bifurcation
      aneurysms in lieu of using two stents in a Y configuration.

PMID- 16582647
TI  - Endoscopic endonasal approaches for repair of cerebrospinal fluid leaks: nine
      year experience.
AB  - OBJECTIVE: To describe surgical endoscopic experience in the repair of
      cerebrospinal fluid leaks treated by transnasal approaches. METHODS: Different
      surgical approaches and techniques in the repair of cranial base defects are
      reviewed in a series of 135 patients. RESULTS: Success rate at first attempt was
      93.3%. Only 9 patients (6.7%) needed a second surgical repair, and in one
      patient, a coronal approach with frontal craniotomy was necessary. In the other
      eight cases, an endoscopic procedure was chosen. Two patients needed a third
      endonasal endoscopic surgical repair, with successful outcome. CONCLUSION: The
      target of endoscopic endonasal technique in the repair of cerebrospinal fluid
      leaks is to ensure a stable duraplasty with the least invasive approach avoiding
      craniotomy. A correct diagnosis surely allows the choice of the best treatment,
      surgical approach, graft, and technique. Our multidisciplinary approach to this
      pathology during these years has been essential to gain our challenging results.

PMID- 16582649
TI  - Single-stage thoracolumbar vertebrectomy with circumferential reconstruction and
      arthrodesis: surgical technique and results in 15 patients.
AB  - OBJECTIVE: Circumferential reconstruction and arthrodesis can be necessary after
      thoracolumbar vertebrectomy. The authors describe a technique for single-stage
      thoracolumbar vertebrectomy with circumferential reconstruction and arthrodesis.
      The surgical results using this technique are reviewed. METHODS: Fifteen patients
      ranging from 14 to 75 years of age underwent single-stage thoracolumbar
      vertebrectomy with circumferential reconstruction and arthrodesis. The
      vertebrectomy was performed through a posterior midline approach. Anterior column
      reconstruction was performed with expandable or nonexpandable cages. Anterior and
      posterolateral arthrodeses used autograft. Posterior segmental instrumentation
      was used in all cases. RESULTS: Fifteen procedures have been performed to date, 4
      for tumor and 11 for fracture. The range of treated levels was T4 to L2 (7
      thoracic spine and 8 lumbar spine levels). One patient was incomplete
      preoperatively (Frankel Grade C) and improved to being intact postoperatively
      (Frankel Grade E), another improved from Frankel Grade C to Frankel Grade D. All
      other patients were neurologically unchanged postoperatively. Mean operative time
      was 4.0 hours. Average blood loss was 1100 ml. Average number of levels fused was
      5.8 (range 4-9). There were four complications: one delayed transient
      neurological deficit after deformity correction, one infection, one postoperative
      myocardial infarction, and one hardware failure. All patients were treated and
      had a good recovery. CONCLUSION: The authors present a method for thoracolumbar
      vertebrectomy, circumferential reconstruction, and arthrodesis performed in a
      single stage, solely via a posterior approach. This is an alternative to anterior
      (i.e., thoracoabdominal and retroperitoneal) and lateral (i.e., lateral
      extracavitary) approaches that can be used for circumferential reconstruction and
      arthrodesis. Potential advantages and pitfalls are discussed.

PMID- 16582650
TI  - Surgical applications to arteriovenous malformations involving the brainstem.
AB  - OBJECTIVE: To evaluate possible applications of microsurgical extirpation to
      arteriovenous malformations (AVMs) involving the brainstem. METHODS: We
      retrospectively reviewed clinical records of 25 patients with AVMs involving
      brainstems who were admitted to our institute from 1984 to 2004. We defined a
      brainstem AVM as an AVM in which some part was located within the brainstem. The
      main location of the nidus was classified into ventral midbrain (n = 3), dorsal
      midbrain (n = 10), pons (n = 5), cerebellopontine angle (n = 6), and medulla
      oblongata (n = 1). Bleeding risks from the AVMs were calculated, and applied
      treatment modalities, respectability, and clinical outcomes were analyzed.
      RESULTS: The annual bleeding and rebleeding risks of brainstem AVMs were 15.1 and
      14.2%, respectively. Total resection was successfully performed in 0 out of 3, 6
      out of 10, 2 out of 5, 6 out of 6, and 0 out of 1 in each of the groups,
      respectively. Stereotactic radiosurgery was applied as a main treatment modality
      in three patients (two ventral midbrain AVMs and one pontine AVM), and after
      microsurgery in one patient with a medulla oblongata AVM. Microsurgery-related
      permanent neurological complications were observed in five patients (one
      postoperative bleeding, one hemiparesis, three hearing deterioration, one
      abducens nerve palsy). During a follow-up period of 8 years (range, 8 mo-15 yr),
      one patient with an untreated pontine AVM died owing to hemorrhage and one
      patient with a subtotally resected dorsal midbrain AVM died owing to an unknown
      etiology 4 years later. CONCLUSION: Surgical resection can be applied with
      considerable, but acceptable, morbidity and mortality in some groups of brainstem
      AVMs with hemorrhagic presentation, particularly dorsal midbrain and
      cerebellopontine angle types, in which most parts of the nidus located sub- or
      extrapially.

PMID- 16582651
TI  - Dual electrode thalamic deep brain stimulation for the treatment of posttraumatic
      and multiple sclerosis tremor.
AB  - OBJECTIVE: To report the results of ventralis intermedius nucleus/ventralis
      oralis posterior nucleus (VIM) plus ventralis oralis anterior (VOA)/ventralis
      oralis posterior (VOP) thalamic deep brain stimulation (DBS) for the treatment of
      posttraumatic and multiple sclerosis tremor. OBJECTIVE: The treatment of
      posttraumatic tremor and multiple sclerosis tremor, by either medication or
      surgery, has proven difficult. Lesions and DBS have had mixed and somewhat
      disappointing results. Previously, we reported the use of two DBS electrodes (one
      at the VIM/VOP border and one at the VOA/VOP border) as effective for the
      treatment of posttraumatic tremor in a single patient. In this study, we report
      the results of this technique on four patients. METHODS: Four patients with
      either posttraumatic tremor (n = 3) or multiple sclerosis tremor (n = 1)
      underwent placement of two DBS electrodes (one at the VIM/VOP border and one at
      the VOA/VOP border). Patients underwent preoperative testing and testing at a
      minimum of 6 months after implantation in four conditions: On VIM DBS/On VOA/VOP
      DBS; On VIM DBS/Off VOA VOP DBS (5 h DBS washout); Off VIM DBS/Off VOA/VOP DBS
      (12 h overnight washout); and Off VIM DBS/On VOA/VOP DBS (5 h DBS washout).
      RESULTS: Each of the patients showed improvements in all four conditions when
      compared with the baseline. All of the improvements were maintained with chronic
      DBS, without tremor rebound. An analysis was performed to determine whether each
      condition was associated with symptom reduction (percentage change). The
      percentage reduction was significant for each condition and measure, despite the
      small number of participants. For the total tremor rating scale score, the Off
      VIM/Off VOA/VOP condition yielded less symptom reduction than the On VIM
      condition or the On VOA/VOP condition. The On VIM and On VOA/VOP conditions did
      not differ significantly from each other in terms of contralateral upper
      extremity symptoms or total clinical score. Activation of both the VIM and
      VOA/VOP electrodes was associated with the greatest symptom reduction.
      CONCLUSION: Tremors, such as those examined in this study, that are refractory to
      medications and have a poor response to VIM DBS monotherapy, may respond
      favorably to VIM plus VOA/VOP DBS. Two electrodes may be better than one for the
      treatment of certain disorders; however, more study will be required to confirm
      this hypothesis.

PMID- 16582652
TI  - Video-assisted thoracoscopic dissection of the brachial plexus: cadaveric study
      and illustrative case.
AB  - OBJECTIVE: Standard surgical approaches to the brachial plexus require an open
      operative technique with extensive soft tissue dissection. A transthoracic
      endoscopic approach using video-assisted thoracoscopic surgery (VATS) was studied
      as an alternative direct operative corridor to the proximal inferior brachial
      plexus. METHODS: VATS was used in cadaveric dissections to study the anatomic
      details of the brachial plexus at the thoracic apex. After placement of standard
      thoracoscopic ports, the thoracic apex was systematically dissected. The
      limitations of the VATS approach were defined before and after removal of the
      first rib. The technique was applied in a 22-year-old man with neurofibromatosis
      who presented with a large neurofibroma of the left T1 nerve root. RESULTS: The
      cadaveric study demonstrated that VATS allowed for a direct cephalad approach to
      the inferior brachial plexus. The C8 and T1 nerve roots as well as the lower
      trunk of the brachial plexus were safely identified and dissected. Removal of the
      first rib provided exposure of the entire lower trunk and proximal divisions.
      After the fundamental steps to the dissection were identified, the patient
      underwent a successful gross total resection of a left T1 neurofibroma with VATS.
      CONCLUSION: VATS provided an alternative surgical corridor to the proximal
      inferior brachial plexus and obviated the need for the extensive soft tissue
      dissection associated with the anterior supraclavicular and posterior subscapular
      approaches.

PMID- 16582653
TI  - Implementation of fiber tract navigation.
AB  - OBJECTIVE: To implement fiber tracking in a common neuronavigation environment
      for routine clinical use to visualize major white matter tracts intraoperatively.
      METHODS: A single-shot, spin-echo diffusion weighted echo planar imaging sequence
      with six diffusion directions on a 1.5 T magnetic resonance scanner was used for
      diffusion tensor imaging. For three-dimensional (3-D) tractography, we applied a
      knowledge-based multiple volume of interest approach. Tracking was initiated in
      each voxel of the initial seed volume in retrograde and orthograde directions
      according to the direction of the major eigenvector by applying a tensor
      deflection algorithm. Tractography results were displayed as streamlines assigned
      direction encoding color. After selecting the fiber tract bundle of interest by
      defining inclusion and exclusion volumes, a 3-D object was generated
      automatically by wrapping the whole fiber tract bundle. This 3-D object was
      displayed along with other contours representing tumor outline and further
      functional data with the microscope heads-up display. RESULTS: In 16 patients
      (three cavernomas, 13 gliomas), major white matter tracts (pyramidal tract, n =
      14; optic radiation, n = 2) were visualized intraoperatively with a standard
      navigation system. Three patients developed a postoperative paresis, which
      resolved in two in the postoperative course. Additional planning time for
      tractography amounted to up to 10 minutes. Comparing the tractography results
      with a fiber bundle generated on a different platform by applying a distortion
      free sequence revealed a good congruency of the defined 3-D outlines in the area
      of interest. CONCLUSION: Fiber tract data can be reliably integrated into a
      standard neuronavigation system, allowing for intraoperative visualization and
      localization of major white matter tracts such as the pyramidal tract or optic
      radiation.

PMID- 16582654
TI  - The utility of intraoperative blood flow measurement during aneurysm surgery
      using an ultrasonic perivascular flow probe.
AB  - OBJECTIVE: Inadvertent vessel compromise is one major cause of unfavorable
      outcome from aneurysm surgery. Existing strategies for intraoperative assessment
      of this complication have potential limitations and disadvantages. We assessed
      the utility of quantitative intraoperative flow measurements using the Transonic
      ultrasonic flow probe (Transonic Systems, Inc., Ithaca, NY) during aneurysm
      surgery. METHODS: Of all aneurysms treated surgically at our institution from
      1998 to 2003, 103 patients with 106 aneurysms were identified in whom
      intraoperative flow measurements were available for analysis. We assessed the
      frequency of flow compromise and clip repositioning and correlated these with
      postoperative angiography and stroke. RESULTS: Significant (>25%) reduction in
      flow rate was apparent in 33 (31.1%) cases, and resulted in clip repositioning in
      27 (25.5%), with return to baseline flow except for two cases with vessel
      thrombosis/dissection. In the other six cases, flow reduction was owing to spasm
      resolving with papaverine (n = 3) or responded to retractor repositioning (n =
      3). In another six (5.7%) cases, unnecessary clip repositioning was avoided (n =
      3) or safe occlusion of the parent vessel for trapping of the aneurysm was
      allowed by confirming adequate distal flow (n = 3). Aneurysms of the basilar,
      middle cerebral, anterior communicating, or carotid terminus were more likely to
      be associated with flow compromise (odds ratio, 4.3; P = 0.03). Postoperative
      angiography corroborated vessel patency in all cases, and no unexpected large
      vessel occlusions or strokes were evident. CONCLUSION: Use of the ultrasonic flow
      probe provides real-time immediate feedback concerning vessel patency. Vessel
      compromise is easier to interpret than with Doppler, and faster/less invasive
      than intraoperative angiography. Intraoperative flow measurement is a valuable
      adjunct for enhancing the safety of aneurysm surgery.

PMID- 16582655
TI  - Application of rapid-sampling, online microdialysis to the monitoring of brain
      metabolism during aneurysm surgery.
AB  - OBJECTIVE: To introduce rapid-sampling microdialysis for the early detection of
      adverse metabolic changes in tissue at risk during aneurysm surgery. METHODS: A
      microdialysis catheter was inserted under direct vision into at-risk cortex at
      the start of surgery. This monitoring was sustained throughout the course of the
      operation, during which intraoperative events, for example, temporary arterial
      occlusion or lobe retraction, were precisely documented. A continuous online flow
      of dialysate was fed into a mobile bedside glucose and lactate analyser. This
      comprises flow-injection dual-assay enzyme-based biosensors capable of
      determining values of metabolites every 30 seconds. RESULTS: Eight patients
      underwent clipping or wrapping of intracranial aneurysms and were monitored. Time
      between events and detection: 9 minutes. Mean change in metabolite value +/-
      standard deviation: temporal lobe retraction lactate, +656 +/- 562 micromol/L (n
      = 7, P < 0.05); glucose, -123 +/- 138 micromol/L (n = 6, P = 0.08). Glucose
      intravenous bolus infusion glucose, +512 +/- 244 micromol/L (n = 5, P < 0.01);
      peak at mean time after bolus, 16 minutes. Temporary proximal clip lactate, +731
      +/- 346 micromol/L (n = 6, P < 0.01); glucose, -139 +/- 96 micromol/L (n = 5, P <
      0.05); mean clip time, 8.6 minutes. CONCLUSION: The technique detects changes 9
      minutes after intraoperative events occur (limited only by probe-to-sensor tubing
      length and dialysate flow rate). This provides reliable information to the
      surgeon and anesthetist promptly. It is a useful method for monitoring glucose
      and lactate in dialysate, particularly when rapid, transient changes in brain
      analyte levels need to be determined and the alternative offline methodology
      would be inadequate.

PMID- 16582656
TI  - Subpectoral implantation of the vagus nerve stimulator.
AB  - OBJECTIVE: To report the technique of subpectoral (SP) implantation of the vagus
      nerve stimulator (VNS) generator. METHODS: We retrospectively reviewed and
      compared demographics and complications from patients receiving either
      subcutaneous (SQ; n = 107) or SP (n = 138) VNS implants, performed by one surgeon
      (WKD) between 1999 and 2003. Selection of implant location was made during the
      preoperative surgeon-patient consultation on the basis of surgeon recommendation
      and patient preference. RESULTS: The standard VNS generator implantation is
      performed within a SQ pocket in the left infraclavicular region of the chest. We
      have modified this technique by placing the generator into a deeper pocket SP,
      beneath the pectoralis major muscle, while tunneling the electrodes SQ in the
      usual fashion. The SP group was substantially younger (median age 19 yr) compared
      with the SQ group (median age 29 yr). At an average follow-up of 52 months for SQ
      implants and 28.4 months for SP implants, there were 2.9% infections per patient
      in the SQ group and 2.5% infections per patient in the SP group. There were three
      cases of excessive generator mobility in the SQ group; no cases occurred in the
      SP group. CONCLUSION: The SP implantation technique provides an attractive
      alternative to SQ VNS implantation. With increased soft tissue coverage, we
      provide improved cosmesis, increased wound durability to tampering and trauma,
      and a comparable infection rate with the SQ group.

PMID- 16582657
TI  - Combined anterior and anterolateral approaches to the cranial base: complication
      analysis, avoidance, and management.
AB  - OBJECTIVE: During the past decade, applications of anterior and anterolateral
      cranial approaches for both benign and malignant pathologies have expanded in
      frequency and application. Complications associated with these procedures impact
      significantly on patient outcome. The primary aim of this study is to detail the
      strategies for complication management and avoidance developed from experience
      with 120 patients who underwent anterior and anterolateral cranial base
      procedures during the past 14 years. METHODS: Between July 1990 and February
      2004, 62 male and 58 female patients underwent 120 combined (neurological surgery
      and otolaryngology joint participation) anterior and anterolateral cranial base
      procedures. Fifty-four percent had malignant pathology, and 46% had benign
      pathology. The approaches taken were transfacial (10%), extended subfrontal
      (33%), lateral craniofacial (23%), and anterior craniofacial (35%). Thirty-day
      morbidity and mortality were analyzed. RESULTS: Twenty (17%) patients experienced
      at least one complication. Malignancy and reoperation, regardless of histology,
      appeared to affect the complication rate. A decline in complications occurred
      with experience, in part because of changes in management that reflected the
      complication experience (25% in Patients 0-31, 18% in Patients 32-70, 10% in
      Patients 71-120). Methodology is detailed for avoidance and management of
      retraction injury, infection, tension pneumocephalus, cerebrospinal fluid leak,
      pericranial flap failure, free flap sizing, dural banding, intracranial
      hypotension, and cerebrovascular events. Individual patient analysis,
      complications timing, and strategy for management are discussed. CONCLUSION:
      Improved patient outcomes for anterior and anterolateral cranial base surgery
      are, in part, directly related to the ability to avoid and manage associated
      complications. Experience, avoidance, and interdiction are key factors in
      complication management.

PMID- 16582658
TI  - Intraoperative magnetic resonance imaging-guided neurosurgery at 3-T.
AB  - OBJECTIVE: Between 1997 and 2004, more than 700 neurosurgical procedures were
      performed in a 1.5-T magnetic resonance-guided therapy suite. During this period,
      the concept of high-field intraoperative magnetic resonance imaging (MRI) was
      validated, as was a new surgical guidance tool, the Navigus (Image-guided
      Neurologics, Melbourne, FL), and its methodology, prospective stereotaxy.
      Clinical protocols were refined to optimize surgical techniques. That
      implementation, the "Minnesota suite," has recently been revised, and a new suite
      with a 3-T MRI scanner has been developed. METHODS: On the basis of experience at
      the initial 1.5-T suite, a new suite was designed to house a 3-T MRI scanner with
      wide surgical access at the rear of the scanner (opposite the patient couch). Use
      of electrocautery, a fiberoptic headlamp, a power drill, and MRI-compatible
      neurosurgical cutlery was anticipated by inclusion of waveguides and
      radiofrequency filter panels that penetrate the MRI suite's radiofrequency
      shield. An MRI-compatible head holder was adapted for use on the scanner table. A
      few items exhibiting limited ferromagnetism were used within the magnetic field,
      taking strict precautions. RESULTS: During the initial procedures (all magnetic
      resonance-guided neurobiopsies), the new suite functioned as anticipated.
      Although metallic artifact related to titanium needles is more challenging at 3 T
      than at 1.5 T, it can be contained even at 3 T. Similar to 1.5 T, such artifact
      is best contained when the device is oriented along B0, the main magnetic field.
      Surgical needles, disposable scalpels, and disposable razors, despite being
      minimally ferromagnetic, were easily controlled by the surgeon. CONCLUSION: An
      intraoperative magnetic resonance-guided neurosurgical theater has been developed
      with a 3-T MRI scanner. Intraoperative imaging is feasible at this field
      strength, and concerns regarding specific absorption rate can be allayed.
      Infection control procedures can be designed to permit neurosurgery within this
      environment. Despite the increase in magnetic field strength, safety can be
      maintained.

PMID- 16582659
TI  - Double reimplantation technique to reconstruct arterial bifurcations with giant
      aneurysms.
AB  - OBJECTIVE: To introduce the double implantation technique, a variation of
      standard radial artery or saphenous vein bypass that can be used to reconstruct
      arterial bifurcations in the management of giant aneurysms with complex branch
      arteries. METHODS: This technique was applied in two patients with giant
      aneurysms. A 74-year-old woman presented with a ruptured thrombotic middle
      cerebral artery aneurysm, and a 24-year-old man presented with an enlarging
      infectious aneurysm of the distal anterior cerebral artery (ACA). RESULTS: In the
      first case, a saphenous vein graft was anastomosed end-to-end to the external
      carotid artery. The temporal M2 middle cerebral artery trunk was disconnected
      from the aneurysm and reimplanted onto the graft with an end-to-side anastomosis.
      The graft was anastomosed end-to-side to the frontal M2 middle cerebral artery
      trunk, and the aneurysm was trapped. Similarly, in the second case, a radial
      artery graft was connected to a proximal ACA branch (anterior internal frontal
      artery) and to the distal pericallosal artery, with reimplantation of the
      callosomarginal artery onto the graft. The aneurysm was occluded proximally with
      a clip. CONCLUSION: The combination of two arterial reimplantations onto a bypass
      graft connected to a proximal donor artery (3 anastomoses overall) reconstructs
      an arterial bifurcation and enables the exclusion of a giant aneurysm. Ischemia
      times are minimized by completing the proximal anastomosis first, successively
      reimplanting efferent arterial trunks distally, and restoring cerebral perfusion
      to reimplanted arteries while other anastomoses are performed. This technique may
      be indicated when critical efferent arteries require revascularization,
      conventional donor arteries are diminutive, the aneurysm has ruptured, or
      intraluminal thrombus requires debulking.

PMID- 16582660
TI  - Anterior cervical discectomy and corpectomy.
AB  - OBJECTIVE: The objective of this review article is to describe the authors'
      operative technique for performing anterior cervical corpectomy and fusion.
      METHODS: The authors reviewed their operative technique and experience to clearly
      detail the general methods utilized to safely and effectively perform anterior
      cervical corpectomy and fusion. Specific nuances peculiar to the authors'
      technique were identified and highlighted. RESULTS: The operative technique for
      anterior cervical corpectomy, including nuances for enhancing ease or outcome of
      surgery, is described in detail. Drawings and photographs are included where
      appropriate to highlight specific aspects of the procedural technique.
      CONCLUSION: Anterior cervical corpectomy and fusion is a well known technique
      that proceeds in a consistent and logical sequence of maneuvers. Specific
      technical nuances at various points enhance the ease and safety of the technique,
      as well as the completeness of the eventual result.

PMID- 16582661
TI  - Anterior supraclavicular approach to the brachial plexus.
AB  - The anterior supraclavicular approach to the brachial plexus is commonly
      indicated in patients with traumatic injuries, tumors, or entrapment of the
      brachial plexus elements. We describe the anatomy and operative technique of this
      approach, which has been used by the senior author (DGK) for the past 30 years.

PMID- 16582662
TI  - Improved technique for harvesting the accessory nerve for transfer in brachial
      plexus injuries.
AB  - OBJECTIVE: The accessory nerve is frequently used as a donor for nerve transfer
      in brachial plexus injuries. In currently available techniques, nerve
      identification and dissection is difficult because fat tissue, lymphatic vessels,
      and blood vessels surround the nerve. We propose a technique for location and
      dissection of the accessory nerve between the deep cervical fascia and the
      trapezius muscle. METHODS: Twenty-eight patients with brachial plexus palsy had
      the accessory nerve surgically transplanted to the suprascapular nerve. To
      harvest the accessory nerve, the anterior border of the trapezius muscle was
      located 2 to 3 cm above the clavicle. The fascia over the trapezius muscle was
      incised and detached from the anterior surface of the muscle, initially, close to
      the clavicle, then proximally. The trapezius muscle was detached from the
      clavicle for 3 to 4 cm. The accessory nerve and its branches entering the
      trapezius muscle were identified. The accessory nerve was sectioned as distally
      as possible. To allow for accessory nerve mobilization, one or two proximal
      branches to the trapezius muscle were cut. The most proximal branch was always
      identified and preserved. A tunnel was created in the detached fascia, and the
      accessory nerve was passed through this tunnel to the brachial plexus. RESULTS:
      In all of the cases, the accessory nerve was easily identified under direct
      vision, without the use of electric stimulation. Direct coaptation of the
      accessory nerve with the suprascapular nerve was possible in all patients.
      CONCLUSION: The technique proposed here for harvesting the accessory nerve for
      transfer made its identification and dissection easier.

PMID- 16582669
TI  - Infectious diseases.

PMID- 16582670
TI  - Current status and future prospects for new therapies for pulmonary tuberculosis.
AB  - PURPOSE OF REVIEW: Nowadays tuberculosis is becoming a worldwide problem, and
      according to the World Health Organization, which declared tuberculosis a global
      health emergency in 1993, each year 8 million people worldwide develop the active
      disease and almost 3 million die. RECENT FINDINGS: Due to this problem there is
      an urgent need for new strategies and drugs to fight against this disease. In
      this context, this review describes promising new classes of compounds against
      tuberculosis that are under study, as well as promising drugs that may soon be
      introduced onto the market. Another subject reported in this review is inhaled
      therapy, an important route under study for delivering antitubercular drugs
      directly to the lungs. SUMMARY: The implications of new drugs and inhaled therapy
      in tuberculosis treatment are fewer toxic side-effects, improved pharmacokinetics
      properties, extensive and potent activity against Gram-positive and Gram-negative
      bacteria, including resistant strains, and a reduction in the total treatment
      time.

PMID- 16582671
TI  - Newer diagnostics for tuberculosis and multi-drug resistant tuberculosis.
AB  - PURPOSE OF REVIEW: This article will review some of the recent developments for
      the rapid diagnosis and detection of drug resistance in tuberculosis. RECENT
      FINDINGS: Tuberculosis remains one of the major causes of death from a single
      infectious agent worldwide. Of great concern for tuberculosis control is the
      emergence of drug resistance since there is no cure for some multidrug-resistant
      strains of M. tuberculosis, and there is concern that they may spread around the
      world, stressing the need for additional control measures such as new diagnostics
      and better drugs for treatment. Recent advances in molecular biology and a better
      understanding of the molecular basis of drug resistance have provided new tools
      for rapid tuberculosis diagnosis. Other non-conventional diagnostic approaches
      have also been proposed. Nucleic acid amplification techniques, both commercial
      and in-house, and non-molecular methods are being evaluated. The overall accuracy
      of most of these tests is promising and some of them can be easily implemented in
      clinical mycobacteriology laboratories. SUMMARY: New genotypic and phenotypic
      methods for rapid diagnosis and detection of drug resistance have been developed
      and tested both in M. tuberculosis strains as well as in clinical samples.
      Further controlled evaluations are necessary in high-endemic countries for their
      eventual implementation in the routine diagnostic systems.

PMID- 16582672
TI  - Recent advances in the medical and surgical treatment of multi-drug resistant
      tuberculosis.
AB  - PURPOSE OF REVIEW: Multi-drug resistant tuberculosis is a serious clinical
      problem. Extension of drug resistance to second-line anti-tuberculosis drugs in
      the form of the W-strain is cause for alarm. There is an urgent need for more
      rapid recognition of multi-drug resistant tuberculosis and newer therapeutic
      agents. This review summarizes the recent advances in the diagnosis and treatment
      of multi-drug resistant tuberculosis including surgery and new developments.
      RECENT FINDINGS: Multidrug resistant tuberculosis therapy is characterized by
      prolonged treatment, high morbidity and mortality, and high relapse rates. New
      diagnostic procedures that include electrophoretic and molecular hybridization
      techniques will allow rapid diagnosis. Several new drugs are currently in various
      phases of development. Moxifloxacin, a respiratory fluoroquinolone, is currently
      in phase III clinical development. New classes of drugs such as
      nitroimidazopyrans (PA-824) and diarylquinolines (R-207910) are exciting based on
      phase I and II data. Immunomodulation with vaccines and interferon-gamma have
      been unhelpful. Surgery is reserved for selected cases only. Cure rates of over
      90% with reasonable morbidity and mortality has been achieved with meticulous
      preoperative preparation, patient selection and careful surgical technique.
      SUMMARY: Newer drugs and defined indications for surgery should provide improved
      cure rates, with reduced duration of treatment for multi-drug resistant
      tuberculosis.

PMID- 16582673
TI  - Tuberculosis vaccines: past, present and future.
AB  - PURPOSE OF REVIEW: The current vaccine against tuberculosis protects against
      severe forms of the disease in children but confers variable effectiveness
      against pulmonary disease. With tuberculosis eradication on the horizon new
      vaccines with better protection than Mycobacterium bovis bacillus Calmette-Guerin
      (BCG) are needed. This review will outline the most promising tuberculosis
      vaccine candidates from selected publications. RECENT FINDINGS: The enormous
      effort of the scientific community in the last 10 years has generated hundreds of
      tuberculosis vaccine candidates. These include sub-unit vaccines and live
      vaccines such as recombinant BCG and other attenuated live vaccines. Some of
      these are being included for the first time in phase I clinical trials. SUMMARY:
      For more than 80 years now no new tuberculosis vaccine has successfully been
      developed. There is now renewed optimism that vaccines superior to BCG can be
      developed in the coming years. The goal is to obtain a new generation of vaccines
      effective against more transmissible forms of tuberculosis. As a first step, good
      candidate vaccines able to boost BCG and improve BCG protection could be a
      reality in the near future. Tuberculosis vaccine candidates, able to replace the
      currently used BCG and make the eradication of tuberculosis feasible, can be
      expected in the mid-term, and live vaccines are reliable and promising
      candidates.

PMID- 16582674
TI  - Nosocomial pneumonia: aetiology, diagnosis and treatment.
AB  - PURPOSE OF REVIEW: This review highlights recent advances in the aetiology of
      nosocomial pneumonia, and in strategies to increase accuracy of diagnosis and
      antibiotic prescription while limiting unnecessary antibiotic consumption. RECENT
      FINDINGS: Bacterial pathogens still cause the bulk of nosocomial pneumonia and
      are of concern because of ever-rising antimicrobial resistance. Yet, the
      pathogenic role of fungal and viral organisms is increasingly recognized. Since
      early appropriate antimicrobial therapy is the cornerstone of an effective
      treatment, further studies have been conducted to improve appropriateness of
      early antibiotic therapy. De-escalation strategies combine initial broad-spectrum
      antibiotics to maximize early antibiotic coverage with a subsequent focusing of
      the antibiotic spectrum when the cause is identified. Invasive techniques
      probably do not alter the immediate outcome but have the potential to reduce
      unnecessary antibiotic exposure. Decisions to stop or change antibiotic therapy
      are hampered due to a lack of reliable parameters to assess the resolution of
      pneumonia. SUMMARY: Increasing antimicrobial resistance in nosocomial pneumonia
      both challenges treatment and mandates limitation of selection pressure by
      reducing antibiotic burden. Treating physicians should be both aggressive in
      initiating antimicrobials when suspecting nosocomial pneumonia but willing to
      discontinue antimicrobials when diagnostic results point to an alternative
      diagnosis. Efforts should be made to limit duration of antibiotic therapy when
      possible.

PMID- 16582675
TI  - Gram-negative bacterial pneumonia: aetiology and management.
AB  - PURPOSE OF REVIEW: Recent articles of clinical and investigational interest on
      Gram-negative pneumonia, particularly hospital-acquired and ventilator-associated
      pneumonia, are reviewed. RECENT FINDINGS: The high rate of respiratory infections
      due to Gram-negative bacteria in late-onset ventilator-associated pneumonia has
      been repeatedly documented. The predominant pathogens are Pseudomonas aeruginosa
      and Acinetobacter baumannii. On the other hand, the frequency of Gram-negative
      bacteria in community-acquired pneumonia and in early-onset ventilator-associated
      pneumonia is increasing. Patients with risk factors for infection with resistant
      pathogens should initially receive a combination therapy that covers a broad
      spectrum, and, as soon as the pathogen and the susceptibilities are available,
      treatment should be simplified to a more targeted one (with the possible
      exception of P. aeruginosa pneumonia). Adequate dosing is of great importance and
      the use of pharmacodynamic/pharmacokinetic principles when prescribing
      antibiotics increases effectiveness. The optimal duration of therapy remains
      unknown; several studies have supported the use of shorter courses of treatment.
      Alternative treatment approaches (e.g. vaccines) are under investigation.
      SUMMARY: The increasing frequency of resistant Gram-negative bacteria and the
      shortage of newer antibiotics in the pipeline with activity against Gram-negative
      bacteria is of concern. Early effective antimicrobial treatment is a key for the
      resolution of infection and improved survival.

PMID- 16582676
TI  - Clinical presentation and management of empyema, lung abscess and pleural
      effusion.
AB  - PURPOSE OF REVIEW: Pleural effusions, lung abscess and empyema remain a commonly
      encountered clinical problem and a significant source of morbidity. The aim of
      this review is to summarize recent developments with emphasis on controlled
      trials. RECENT FINDINGS: There is wide variation in the management of infectious
      pleural effusions, partly because of the relative lack of randomized controlled
      trials. The recent MRC/BTS UK controlled trial of interapleural streptokinase for
      pleural infection assessed the efficacy of intrapleural streptokinase compared
      with placebo in complicated parapneumonic effusions. The study showed no
      difference in the primary end point, mortality, or in the need for surgery or
      length of the hospital stay among patients with pleural infection. The first
      large report published for over a decade has suggested that the bacteriological
      characteristics of lung abscess have changed. SUMMARY: The major recent
      development in the management of pleural infections is the finding that we should
      dampen the ardor for the routine use of fibrinolytic agents in all patients with
      pleural infections. We strongly recommend the necessity for additional, well
      designed trials to help determine optimal care for these seriously ill patients.

PMID- 16582677
TI  - Parasitic diseases of the respiratory tract.
AB  - PURPOSE OF REVIEW: The human pulmonary system can be affected by a variety of
      parasites. This review focuses on the most common parasitic infestations
      involving the lung, except for protozoon disease. RECENT FINDINGS: In many
      parasitic lung conditions, the clinical manifestations and the imaging findings
      are non-specific and can make diagnosis challenging. Hydatid disease and
      paragonimiasis involve the lung directly. Chronic schistosomiasis can lead to
      pulmonary hypertension. Strongyloides stercoralis infestation is capable of
      transforming into a fulminant fatal disease. In many types of nematode
      infestations, the pulmonary phase can cause acute eosinophilic pneumonia. Chest
      radiographs of patients with paragonimiasis and dirofilariasis can cause
      diagnostic confusion. Cases of tropical pulmonary eosinophilia typically present
      with refractory bronchial asthma. Most of these diseases are initially diagnosed
      by detecting eggs or larvae in stool, sputum, pleural fluid or tissue, and are
      confirmed by serologic testing. Cystic hydatid disease generally requires
      surgical treatment, whereas almost all other parasitic lung conditions can be
      treated medically. SUMMARY: Although most parasites that affect the lung are
      endemic to tropical and subtropical regions, immigration and travel practices
      have resulted in transfer of these diseases to other areas. It is important for
      physicians to know the epidemiologic characteristics, clinical presentations, and
      treatments of choice for these conditions.

PMID- 16582678
TI  - Fungal respiratory disease.
AB  - PURPOSE OF REVIEW: Fungal respiratory disease is associated with a high mortality
      in immunocompromised patients. This review aims to describe the recent advances
      in the aetiology, clinical presentation, diagnosis and management of fungal
      respiratory disease. RECENT FINDINGS: Invasive aspergillosis is an uncommon
      complication of hematopoietic stem cell transplants and solid-organ transplants
      but continues to be associated with poor outcome. Isolation of Aspergillus spp.
      from respiratory samples preceded acute rejection in lung-transplantation
      recipients. Molecular typing suggested that there was a very weak correlation
      between the environmental and patient isolates of Aspergillus fumigatus in
      invasive pulmonary aspergillosis. Serological and molecular detection of
      Aspergillus antigens or fungal DNA may improve the diagnosis of pulmonary
      aspergillosis, but the sensitivity is variable and more studies are needed.
      Voriconazole and caspofungin are choice to Aspergillus and Candida infection,
      especially to azole-resistant Candida spp. Treatment combining amphotericin B
      preparations, early surgical resection of infected tissue and discontinuation of
      immunosuppressive treatment may improve prognosis of mucormycosis. SUMMARY:
      Invasive filamentaous fungal infections of lung remain important causes of death
      in immunocompromised patients. Development of new early diagnostic tools and well
      designed multicenter evaluations of diagnostic methods and therapeutic regimens
      available at present are the important work in the next 2-3 years.

PMID- 16582679
TI  - Actinomycoses and Nocardia pulmonary infections.
AB  - PURPOSE OF REVIEW: Actinomycosis and nocardiosis are uncommon pulmonary
      infections with distinct morphologic features. Both infections most commonly
      present as chronic, debilitating illnesses with radiographic manifestations
      simulating lung cancer or tuberculosis. Immunocompromised hosts, however, may
      develop fulminant disease resembling acute bacterial pneumonia. The purpose of
      this review is primarily to review the clinical features, diagnosis, and
      management of actinomycosis and nocardiosis. RECENT FINDINGS: Treatment of
      actinomycosis is usually simple, requiring long-term, high-dose intravenous
      penicillin. Short-course chemotherapy, however, has recently been reported to be
      successful. Pulmonary nocardiosis is an important cause of opportunistic
      infection in immunosuppressed patients, and the incidence of this infection is
      increasing. The sulfonamides are still first-line agents in the management of
      nocardiosis, but resistance is most common among N. farcinica and N.
      otitidiscaviarum isolates. Carbapenems should be used as an alternative treatment
      for severely ill patients. Broth microdilution, E-test (AB Biodisk, Solna,
      Sweden) and BACTEC (Becton Dickinson, Sparks, Maryland, USA) radiometric method
      may be more useful in the routine clinical laboratory for antimicrobial testing
      of aerobic actinomycetes. SUMMARY: The practical distinction between the two
      diseases is in the matter of therapy. Diagnosis depends on a high degree of
      suspicion so as to alert the microbiology and pathology laboratories to employ
      special methods to identify the organisms. Early recognition and prompt treatment
      usually results in complete cure.

PMID- 16582680
TI  - Uncommon respiratory pathogens.
AB  - PURPOSE OF REVIEW: In many cases, the specific pathogen responsible for a
      respiratory infection is not identified and can lead to improper medical
      treatment, increased duration of illness, and possibly contributes to the
      development of antibiotic resistance. Molecular-based diagnostic methodologies
      have significantly improved our ability to identify common respiratory pathogens;
      these techniques are not useful, however, when a novel pathogen is responsible
      for the infection and clinicians must rely on differential diagnosis for the
      treatment of patients. RECENT FINDINGS: New pathogens previously not associated
      with human infections have been identified in the past few years. In addition,
      new strains of bacteria and viruses have emerged as the causative agents of
      pneumonia and acute respiratory distress. Protozoans and saprophytic fungi, which
      are not normally associated with respiratory infection, have also emerged as
      respiratory pathogens particularly in individuals with AIDS or in those who are
      otherwise immunocompromised. SUMMARY: This review discusses the recent literature
      on newly described respiratory pathogens as well as opportunistic pathogens that
      can infect the respiratory system of immunocompromised individuals. The studies
      referenced here reveal the need for expanded laboratory tests and highly trained
      microbiologists in clinical laboratories worldwide.

PMID- 16582681
TI  - Bibliography. Current world literature. Infectious diseases.

PMID- 16582683
TI  - Update on nonsteriodal anti-inflammatory drugs.
AB  - PURPOSE OF REVIEW: This review addresses recent concerns about the cardiovascular
      safety of nonsteroidal anti-inflammatory drugs, the disease-modifying role of
      these drugs in ankylosing spondylitis, and their use in the understudied
      pediatric population. RECENT FINDINGS: Several recent observational and
      controlled studies highlight the cardiovascular toxicity of rofecoxib, celecoxib,
      parecoxib, valdecoxib and naproxen. Concerns about cardiovascular safety raise
      questions about the chronic use of nonsteroidal anti-inflammatory drugs in
      patients with rheumatic diseases, including children. The risks of these drugs in
      the pediatric population are not well known and this review addresses the limited
      data available concerning nonsteroidal anti-inflammatory drug use in children. A
      recent trial in ankylosing spondylitis patients demonstrated continuous
      nonsteroidal anti-inflammatory drug use reduced the rate of syndesmophyte
      formation, suggesting that they may have a disease-modifying role in these
      patients. SUMMARY: Nonsteroidal anti-inflammatory drugs have been in the
      spotlight this year. While preliminary evidence has supported novel roles for
      these drugs in ankylosing spondylitis and in cancer prevention, accumulating
      evidence shows that some cyclooxygenase-2 and perhaps all nonsteroidal anti
      inflammatory drugs are associated with cardiovascular toxicity. Further research
      is needed to understand the magnitude and mechanism of this risk. Clinicians are
      compelled to weigh carefully the benefits and risks of therapy. Concerns about
      safety are balanced by optimism about their potential role in delaying the
      progression of ankylosing spondylitis.

PMID- 16582684
TI  - Novel therapeutics for systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: This review provides an update on recently explored therapies
      in systemic lupus erythematosus and introduces novel therapeutic approaches under
      consideration. Recent advances in our understanding of systemic lupus are
      highlighted as well, as these must now inform consideration of therapeutics.
      RECENT FINDINGS: Many therapeutic strategies have been shown to be beneficial in
      murine models of lupus. Compounds that inhibit cellular signaling in response to
      autoantigens or other triggers and protocols that reconstitute the immune
      repertoire to diminish autoreactivity are now entering clinical trials. SUMMARY:
      Requirements for novel approaches in lupus include improved efficacy and lower
      toxicity than current therapies, with the goal to reduce tissue damage while
      preserving immunocompetence.

PMID- 16582685
TI  - Advances in the therapy of idiopathic inflammatory myopathies.
AB  - PURPOSE OF REVIEW: To review progress in areas pertinent to the development of
      better therapies for the idiopathic inflammatory myopathies. RECENT FINDINGS: New
      classification criteria for the idiopathic inflammatory myopathies have been
      proposed in an effort to define disease subsets with more uniform prognoses and
      responses to therapy. Diseases that may mimic the idiopathic inflammatory
      myopathies can be differentiated more accurately with molecular testing and
      biochemical and immunohistochemical analysis of muscle tissue. Advances in our
      understanding of the pathogenesis of the idiopathic inflammatory myopathies have
      served to identify potential new therapeutic targets. International collaborative
      study groups have reached consensus on outcome measures and on the optimal design
      of clinical trials in the idiopathic inflammatory myopathies. Tumor necrosis
      factor-alpha antagonists, rituximab, and the calcineurin inhibitors are being
      used to treat the idiopathic inflammatory myopathies, but their efficacy has not
      yet been tested in randomized clinical trials. SUMMARY: Future advances in the
      development of therapies for the idiopathic inflammatory myopathies have been
      enabled by recent progress in myositis classification, differential diagnosis,
      basic science, and clinical trial design. Preliminary studies suggest that
      calcineurin inhibitors, tumor necrosis factor antagonists, and rituximab may be
      effective treatments.

PMID- 16582686
TI  - Antiphospholipid syndrome.
AB  - PURPOSE OF REVIEW: To review the recently published studies that can guide
      physicians in the management of persistently antiphospholipid antibody (aPL)
      positive patients. RECENT FINDINGS: Two recent prospective randomized controlled
      trials of two intensities of warfarin concluded that both moderate and high
      intensity anticoagulation are similarly protective in antiphospholipid syndrome
      patients after the first thrombosis. Despite lack of controlled studies, there is
      experimental evidence that hydroxychloroquine and statins may play a role in the
      management of aPL-positive patients. In the mouse model of antiphospholipid
      syndrome that involves the injection of high-titer antiphospholipid syndrome
      human serum, complement activation is essential in aPL-mediated fetal loss and
      heparin prevents aPL-induced complement activation. SUMMARY: Primary thrombosis
      prevention in persistently aPL-positive individuals lacks an evidence-based
      approach; elimination of reversible thrombosis risk factors and prophylaxis
      during high-risk periods is crucial. Secondary thrombosis prevention in
      persistently aPL-positive individuals lacks a risk-stratified approach; although
      the current recommendation is life-long warfarin, the necessity, duration, and
      the intensity of warfarin are still debated. Catastrophic antiphospholipid
      syndrome patients usually receive a combination of anticoagulation,
      corticosteroids, intravenous immunoglobulin, and plasma exchange; there is a
      clear need to test new agents. A common strategy to prevent fetal loss in aPL
      positive patients with history of pregnancy morbidities is low-dose aspirin and
      heparin; if patients fail this regimen, the next step is the addition of
      intravenous immunoglobulin although this is not supported by controlled studies.
      Currently, there is no evidence that anticoagulation is effective for
      nonthrombotic manifestations of antiphospholipid antibodies.

PMID- 16582687
TI  - Crystal-induced arthropathies: recent investigative advances.
AB  - PURPOSE OF REVIEW: To highlight recent investigations that have stimulated
      renewed interest in crystal-induced arthropathies. RECENT FINDINGS: Specific diet
      related and alcohol-related risks for gout have been clarified, and alternative
      urate-lowering treatments likely to benefit patients with difficult-to-treat gout
      are in development. Progress toward understanding mechanisms underlying the renal
      deficits defining most cases of gout includes characterization of a urate
      specific renal tubule transporter explaining many aspects of renal uric acid
      handling and identification of mutations in the UMOD gene, resulting in altered
      uromodulin protein in the gout-associated disorders familial juvenile
      hyperuricemic nephropathy and medullary cystic kidney disease type 2. A genetic
      marker associated with the risk for severe allopurinol toxicity has been
      reported. Hyperuricemia and gout are increasing in incidence, as is complicated
      gout, especially among the elderly and patients with cardiovascular and renal
      comorbidities, organ transplants, or complex concomitant medication regimens.
      Asymptomatic hyperuricemia is clearly associated with hypertension, chronic
      kidney disease, cardiovascular disease, and the insulin resistance syndrome, and
      the pathogenetic significance of these associations is under intensive study.
      Mutation in the ANKH gene has been found among some patients with sporadic as
      well as familial calcium pyrophosphate deposition disease. SUMMARY: The results
      of these clinical, epidemiologic, experimental, and therapeutic investigations
      presage advances in the management of crystal-induced arthropathies.

PMID- 16582688
TI  - An update on osteoarthritis therapeutics.
AB  - PURPOSE OF REVIEW: This review addresses recent major developments in symptomatic
      therapy and the principles of disease modification in osteoarthritis. It
      emphasizes issues that are of importance to the practicing clinician at a time
      when researchers in the field are trying to improve ways not only to provide
      symptomatic relief but also to slow disease progression. RECENT FINDINGS: The
      past year has led to a reassessment of the role of cyclo-oxygenase-2 inhibitors
      in osteoarthritis therapy and has yielded new information on nutriceuticals such
      as glucosamine. The relative efficacy of intra-articular injections of agents
      such as corticosteroid and hyaluronic acid preparations has been assessed. In
      addition, reports on trials of potentially disease-modifying agents for
      osteoarthritis have been published. SUMMARY: Because the therapeutic options have
      been reduced over the past year and the role of nutritional supplements remains
      unclear, the clinician is faced with a need to reassess osteoarthritis therapy.
      Although no practical disease-modifying agent for osteoarthritis has been
      identified, reports such as the recent doxycycline trial reviewed herein provide
      hope that continued research will soon yield a therapeutic model similar to that
      used in rheumatoid arthritis, for which some therapeutic agents achieve disease
      modification and other agents can be added as needed for symptomatic relief.

PMID- 16582689
TI  - New concepts in the pathogenesis and treatment of rheumatoid arthritis.

PMID- 16582690
TI  - Synovial cell activation.
AB  - PURPOSE OF REVIEW: Modern molecular biology offers a unique opportunity to gain a
      comprehensive picture of gene expression in a disease state. This review presents
      recent findings in the field of synovial fibroblast biology contributing to
      knowledge of the pathogenesis of rheumatoid arthritis. RECENT FINDINGS: Recently
      it has become apparent that innate immune response pathways play a critical role
      in driving synovial activation and contribute significantly to the turnover of
      leukocytes in the synovial compartment. In addition, microparticles have been
      identified as a new class of potent mediators, broadening the known spectrum of
      cell-derived modulators in the joint. Numerous research groups gained new
      insights into detailed molecular mechanisms leading to the invasiveness of
      rheumatoid arthritis synovial fibroblasts, the disturbance in the regulation of
      apoptosis, and synovial cell-cell and cell-matrix interactions. SUMMARY: The key
      role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis has been
      highlighted by the fact that these cells not only are the main executors of
      cartilage and bone destruction but also modulate numerous interactions in
      rheumatoid joints. Moreover, it has become evident that integration of a large
      body of information is indispensable to get a comprehensive outlook on synovial
      activation in the pathology of rheumatoid arthritis.

PMID- 16582691
TI  - Role of adhesion molecules in synovial inflammation.
AB  - PURPOSE OF REVIEW: The ability of cells to adhere to other cells and
      extracellular matrix (ECM) through cellular adhesion molecules (CAMs) is central
      to tissue remodeling and inflammation. This review discusses the potential role
      of CAMs in development of synovial inflammation through regulating the
      recruitment of inflammatory cells via endothelial-leukocyte interactions, the
      organization and activation of leukocytes in the synovial sublining, and the
      formation and behavior of the hyperplastic synovial lining. RECENT FINDINGS: Over
      the past several years valuable insight has been gained into the role of cell
      cell and cell-ECM adhesive interactions in synovial organization and
      inflammation. Recently, cadherin-11 was identified on fibroblast-like
      synoviocytes and has been demonstrated to play a central role in synovial lining
      organization. Furthermore, studies using animal models of inflammatory arthritis
      have demonstrated critical roles for E- and P-selectins, CD11a/CD18 [lymphocyte
      function-associated antigen (LFA)-1], alpha4beta1 integrin, and cadherin-11 in
      the development of synovial inflammation. SUMMARY: Cell-cell and cell-ECM
      interactions through CAMs play an important role in synovial inflammation. Future
      studies of CAMs are needed to define more thoroughly their role in synovial
      inflammation and their potential as therapeutic targets in the treatment of
      rheumatoid arthritis and related inflammatory arthritic conditions.

PMID- 16582692
TI  - Interleukin-6 in rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: Recent progress in cytokine studies has clarified the
      pathological roles played by cytokines and provided key evidence that
      antagonizing their actions can be therapeutic. The pathogenesis of rheumatoid
      arthritis, an autoimmune inflammatory disease, involves inflammatory cytokines
      such as tumour necrosis factor-alpha, interleukin-1 and interleukin-6. Anti
      tumour necrosis factor-alpha and anti-interleukin-1 therapies have been used
      successfully to treat rheumatoid arthritis, but they are not consistently
      effective. We therefore need further therapies for this refractory disease.
      Interleukin-6 is another target molecule for blockade in the treatment of
      rheumatoid arthritis. Tocilizumab is a humanized antihuman interleukin-6 receptor
      monoclonal antibody designed to block the actions of interleukin-6. This review
      addresses the pathological significance of interleukin-6 and the current status
      of anti-interleukin-6 therapy for rheumatoid arthritis. RECENT FINDINGS: The
      safety and efficacy of tocilizumab have been demonstrated in clinical trials
      conducted in patients with rheumatoid arthritis and other autoimmune inflammatory
      diseases, such as juvenile idiopathic arthritis and Crohn's disease. SUMMARY:
      Clinical studies have demonstrated the pathological significance of interleukin-6
      and the safety and efficacy of anti-interleukin-6 therapy with tocilizumab.
      Blockade of interleukin-6 - the second generation of anticytokine therapy - may
      be a promising treatment for rheumatoid arthritis.

PMID- 16582693
TI  - Early rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: This review provides novel and updated information on
      pathogenesis, referral, and clinical characteristics as well as therapeutic
      approaches in early rheumatoid arthritis. RECENT FINDINGS: Early referral is
      important, but new classification criteria for early rheumatoid arthritis need to
      be elaborated. Predictive markers for rheumatoid arthritis are still confined to
      autoantibodies; respective algorithms have been presented. Other biomarkers will
      still have to prove their usefulness. Magnetic resonance imaging and sonography
      do not appear to sufficiently distinguish between early rheumatoid and
      nonrheumatoid arthritis. Rheumatoid arthritis has become milder at presentation
      in recent years. In its very early stages, the cytokine profile reflects T-cell
      activation and switches to abundant proinflammatory cytokines thereafter. Disease
      modifying antirheumatic drugs plus glucocorticoids are highly effective, as is
      early use of tumor necrosis factor blockers plus methotrexate. Tight control of
      disease activity and subsequent therapeutic adjustments are highly effective.
      Disease activity indices that are simple to calculate have been presented and
      validated. Early intensive therapy may lead to decrease in disability and cost
      reduction in rheumatoid arthritis. SUMMARY: Understanding of early arthritis is
      increasing, especially in prognostic and therapeutic respects, and new treatment
      strategies appear to improve the outcome in patients with early arthritis.
      Nevertheless, much remains to be studied to better address the issue of early
      rheumatoid arthritis.

PMID- 16582695
TI  - Bibliography. Current world literature. Clinical therapeutics.

PMID- 16582694
TI  - Cardiovascular disease in rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: Individuals with rheumatoid arthritis are at increased risk
      for morbidity and mortality from cardiovascular disease (CVD). The purpose of
      this review is to discuss recent advances in our understanding of the
      pathogenesis, prevalence, treatment, and prevention of accelerated
      atherosclerotic disease in rheumatoid arthritis. RECENT FINDINGS: Recent reports
      have highlighted the increased risk for silent myocardial infarction and sudden
      death in rheumatoid arthritis, and the potential roles of traditional and
      nontraditional risk factors for CVD, including abnormal revascularization of
      damaged peripheral blood vessels and genetic polymorphisms. Several studies have
      also added important information on the possible role of anti-tumor necrosis
      factor-alpha therapy, other disease modifying antirheumatic drugs, and
      nonsteroidal anti-inflammatory drugs in decreasing CVD risk. SUMMARY: The
      pathogenic mechanisms involved in accelerated cardiovascular complications in
      rheumatoid arthritis appear to be complex and multifactorial. Both traditional
      and nontraditional risk factors potentially contribute to the increased
      cardiovascular risk. Good control of the inflammation, immunologic disturbances,
      and metabolic changes seen in rheumatoid arthritis are crucial in the prevention
      of this potentially lethal complication. There is a need for heightened awareness
      of the increased risk for silent ischemia, early myocardial infarction, and
      sudden death. Further exploration of the mechanisms of vascular repair and their
      potential role in premature atherosclerosis is needed.

PMID- 16582696
TI  - CAM--it is not just watercress sandwiches anymore.

PMID- 16582697
TI  - CCMC's research uncovers latest trends in case management practice.

PMID- 16582698
TI  - Evaluating chiropractic care/records.

PMID- 16582699
TI  - Case managers' roles and functions: Commission for Case Manager Certification's
      2004 research, part II.
AB  - The Commission for Case Manager Certification (CCMC) conducted its third case
      managers' role and functions study in 2004 for the purpose of validating the
      currency and relevancy of the certified case manager examination. The results of
      this study are shared in an article of 2 parts. Part I, which was published in
      the previous issue of this journal, discussed the process the CCMC used for the
      development of the Case Managers' Role and Functions Survey Instrument and the
      identification of new 6 essential functions and 6 knowledge areas that describe
      case management practice. These findings were based on the survey of a large
      national sample of practicing case managers. Part II continues the analysis of
      the results and focuses on identifying the empirical (statistically derived)
      activity and knowledge domains of case management practice, using exploratory
      factor analysis. It discusses the similarities and differences found among
      various subgroups of case managers who were compared on the basis of certain
      demographic variables. In addition, Part II summarizes future changes in the
      field of case management as perceived by those who participated in the study.

PMID- 16582701
TI  - A nursing case management program for low-income high-risk diabetic clients: a
      projected cost-benefit analysis.
AB  - Case management has been widely promoted as a method that can improve clinical
      outcomes and reduce healthcare costs. This article describes a cost-benefit
      analysis for a proposed nursing case management program that provides care for a
      low-income high-risk diabetic population in a rural county. Industry trends,
      objectives and functions of the case management program, timeline, financial
      plan, and cost analysis are described. The analysis indicated a potential net
      savings of 149,544 dollars annually. This would be a significant cost savings for
      the healthcare provider and funding source.

PMID- 16582703
TI  - The PLISSIT Model: care and management of patients' psychosexual needs following
      radical surgery.
AB  - Patients who have undergone invasive medical procedures requiring radical body
      changes often experience feelings of worthlessness and particularly negative
      feelings about their sexuality. Their initial contact with the healthcare team is
      frequently a nurse who may be poorly equipped, too busy, or too embarrassed to
      help address the patients' sexual issues; therefore, vital information may be
      lost to the healthcare team. The PLISSIT Model offers nurses or case managers a
      concise framework for intervention to address patients' concerns at the earliest
      stages of their distress, and helps assure informed feedback to the healthcare
      team regarding the patients' sexual issues.

PMID- 16582705
TI  - Paranoia or preparedness?

PMID- 16582704
TI  - To die or not to die.
AB  - This article presents the author's personal reflections and experiences in
      providing case management for patients with end-of-life issues. Through case
      examples and practical guidelines, the reader will gain an insight into dealing
      with terminal states in the acute care setting. References were drawn from recent
      literature on the subject, and were the stimulus to this piece.

PMID- 16582708
TI  - Know your number: CKD patients take active role in treatment.

PMID- 16582707
TI  - Patient-centered case management in today's healthcare.

PMID- 16582709
TI  - Rehabilitation as a model for case management.

PMID- 16582720
TI  - Marjolin's ulcer: when healing goes awry.

PMID- 16582721
TI  - Shutting down shingles.

PMID- 16582722
TI  - Taking a closer look at acute otitis media in kids.

PMID- 16582723
TI  - Teaching your patient to irrigate a colostomy.

PMID- 16582724
TI  - Take steps to protect your patient from falls.

PMID- 16582726
TI  - Show no restraint.

PMID- 16582725
TI  - Light can wreak havoc on CVCs.

PMID- 16582743
TI  - Shades of sedation: learning about moderate sedation and analgesia.

PMID- 16582734
TI  - Can mononucleosis damage the liver?

PMID- 16582745
TI  - Listening to the silence.

PMID- 16582746
TI  - Learning from Katrina.

PMID- 16582748
TI  - First aid for amputation.

PMID- 16582747
TI  - Patient education series. Osteoporosis.

PMID- 16582749
TI  - Understanding the new AHA guidelines, part I.

PMID- 16582750
TI  - Bladder cancer: revealing news about a hidden threat.

PMID- 16582760
TI  - Combination drugs...

PMID- 16582751
TI  - Best-practice interventions: keeping central line infection at bay.

PMID- 16582762
TI  - Myths & facts... about brown recluse spider bites.

PMID- 16582767
TI  - Action stat. Epiglottitis.

PMID- 16582768
TI  - Patient safety in the office-based setting.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Discern the importance of the physician's office administrative capacity.
      2. Recognize the necessity of a system for quality assessment. 3. Assess which
      procedures are safe in the office-based setting. 4. Know the basic steps to
      properly evaluate patients for office-based plastic surgery. BACKGROUND: At least
      44,000 Americans die annually as a result of preventable medical errors. Medical
      mistakes are the eighth leading cause of death in the United States, costing
      between $54.6 billion and $79 billion, or 6 percent of total annual national
      health care expenditures. Office-based procedures comprise a 10-fold increase in
      risk for serious injury or death as compared with an ambulatory surgical
      facility. METHODS: This article reviews the literature on office-based patient
      safety issues. It places special emphasis on the statements and advisories
      published by the American Society of Plastic Surgeons' convened Task Force on
      Patient Safety in Office-Based Settings. This article stresses areas of increased
      patient safety concern, such as deep vein thrombosis prophylaxis and liposuction
      surgery. RESULTS: The article divides patient safety in health care delivery into
      three broad categories. First, patient safety starts with emphasis at the
      administrative level. The physician or independent governing body must develop a
      system of quality assessment that functions to minimize preventable errors and
      report outcomes and errors. Second, the clinical aspects of patient safety
      require that the physician evaluate whether the procedure(s) and the patient are
      proper for the office setting. Finally, this article gives special attention to
      liposuction, the most frequently performed office-based plastic surgery
      procedure. CONCLUSIONS: Patient safety must be every physician's highest
      priority, as reflected in the Hippocratic Oath: primum non nocere ("first, do no
      harm"). In the office setting, this priority requires both administrative and
      clinical emphasis. The physician who gives the healing touch of quality care must
      always have patient safety as the foremost priority.

PMID- 16582769
TI  - Breast reconstruction following subcutaneous mastectomy for cancer: a critical
      appraisal of the nipple-areola complex.
AB  - BACKGROUND: Subcutaneous mastectomy for women with advanced breast cancer has
      been historically controversial because of the increased risk for tumor
      recurrence. Despite this, some women remain interested in this method of
      treatment as a means of preserving the appearance of the breast and nipple-areola
      complex. Several studies have evaluated the feasibility of subcutaneous
      mastectomy; however, there has been no study that has critically analyzed the
      aesthetic outcome of the nipple-areola complex following this approach. METHODS:
      Over a 14-month interval, 12 women had subcutaneous mastectomy with preservation
      of the nipple-areola complex. The reconstruction was unilateral in 10 women and
      bilateral in two women, totaling 14 breasts. The mastectomy was for cancer in 11
      and for prophylaxis in three breasts. Outcomes were assessed based on the
      sensation, appearance, and secondary procedures of the nipple-areola complex, and
      tumor recurrence and patient satisfaction. RESULTS: Of the five parameters,
      sensation was present in six breasts (42.9 percent), delayed healing was noted in
      four breasts (28.6 percent), symmetry with the contralateral breast was achieved
      in five of 10 women (50 percent) following unilateral reconstruction, tumor
      recurrence was noted in three of 11 breasts (27.3 percent), and secondary
      procedures related to the nipple-areola complex were necessary in five of the 14
      breasts (35.7 percent). Outcome was graded as excellent in three, good in eight,
      and poor in three breasts. CONCLUSION: This study has demonstrated that aesthetic
      outcome of the nipple-areola complex is variable following subcutaneous
      mastectomy and immediate breast reconstruction. However, patient satisfaction was
      graded as good to excellent in 11 of 14 breasts (78.6 percent). Subcutaneous
      mastectomy with flap reconstruction results in fewer secondary procedures and
      improved aesthetic outcome when compared with implant reconstruction.

PMID- 16582770
TI  - Critical analysis of reduction mammaplasty techniques in combination with
      conservative breast surgery for early breast cancer treatment.
AB  - BACKGROUND: Although reduction mammaplasty is a well-described technique for
      aesthetic purposes, there are few previous reports regarding its application and
      clinical outcome following conservative breast surgery reconstruction. The
      purpose of this study was to analyze the feasibility of the technique and its
      outcome following conservative breast surgery. METHODS: Oncologic data and
      information on age, body mass index, smoking history, and comorbid conditions
      were collected. Reconstructed and opposite breast complications were evaluated.
      Reduction mammaplasty was indicated to reconstruct moderate breast defects in
      patients with enough remaining breast tissue. Mean follow-up was 22 months.
      RESULTS: Seventy-four patients underwent immediate reduction mammaplasty
      following breast-conserving surgery. In 55.4 percent of patients, tumors measured
      2 cm or less (T1) and in 47.2 percent they were located in the upper outer
      quadrants. Breast complications occurred in 13 patients (17.6 percent), with skin
      necrosis in six (8.1 percent), infection in two (2.7 percent), partial areola
      necrosis in two (2.7 percent), dehiscence in two, and total areola necrosis in
      one (1.35 percent). Late complications represented by skin lesions and fat
      necrosis were observed in five patients (6.8 percent). Obese patients and smokers
      had a significantly higher rate of reconstructed breast complications compared
      with the normal/overweight patients (p = 0.002) and nonsmokers (p = 0.043). No
      significant association between complications and age, hypertension, diabetes,
      axillary lymph node dissection, or chemotherapy was found. CONCLUSIONS: Reduction
      mammaplasty is a consistent technique for reconstruction following breast
      conserving surgery. Complications are more often observed in the reconstructed
      breast, and obese patients and smokers are higher risk patients.

PMID- 16582772
TI  - A comparison of postoperative pain between DIEP and extended latissimus dorsi
      flaps in breast reconstruction.
AB  - BACKGROUND: The senior author (A.P.) has performed 70 consecutive breast
      reconstructions over 3 years using the free deep inferior epigastric perforator
      (DIEP) and pedicled extended latissimus dorsi flaps. This study set out to
      compare these two methods of reconstruction by looking at postoperative morphine
      requirements and lengths of stay in hospital. METHODS: Patient notes were
      retrospectively reviewed and the total morphine used by patient-controlled
      analgesia was measured. RESULTS: The mean morphine per kilogram required by
      patients who had DIEP flaps (0.21 mg/kg; n = 22) was significantly less than the
      amount required by patients who had extended latissimus dorsi flaps (0.47 mg/kg;
      n = 48; p < 0.001). An observed trend also revealed that DIEP flap patients
      remained in hospital for less time compared with extended latissimus dorsi flap
      patients, although the difference was not significant (p > 0.01). CONCLUSIONS:
      This study shows that DIEP flap patients require less postoperative morphine and
      therefore might experience less pain than extended latissimus dorsi flap
      patients. DIEP flap patients may also leave the hospital sooner.

PMID- 16582773
TI  - High-frequency ultrasound: a useful tool for evaluating the abdominal wall
      following free TRAM and DIEP flap surgery.
AB  - BACKGROUND: This is the first study to use a standardized ultrasound protocol to
      evaluate hernia and abdominal wall laxity following free transverse rectus
      abdominis myocutaneous (TRAM) and deep inferior epigastric perforator (DIEP) flap
      surgery. METHODS: All patients who underwent free TRAM and DIEP flap surgery
      performed by the senior author between the years 1994 and 2003 were recruited for
      physical examination and ultrasound of the abdominal wall for the dynamic
      evaluation of hernia and abdominal wall laxity. RESULTS: A total of 25 of 28
      patients were followed up (89 percent). Eleven were in the DIEP flap group (44
      percent) and 14 were in the free TRAM flap group (56 percent). Age- and body
      habitus-matched female volunteers (n = 12) were also used in this study. The mean
      follow-up was 3.8 years (range, 0.8 to 8.2 years). Although the kappa coefficient
      was +1 for detection of hernia on physical examination between two independent
      examiners, the interobserver correlation was poor for detection of bulges (kappa
      coefficient, +0.53). Ultrasound showed that abdominal wall laxity was
      statistically highest in the upright position, followed by 30 degrees of truncal
      flexion, and lowest in the supine position. The amount of abdominal wall laxity
      detected by ultrasound was significantly higher in the free TRAM flap group than
      in the free DIEP flap group. Two hernias were detected in the TRAM flap group by
      ultrasound and one hernia was previously known in the DIEP flap group.
      CONCLUSION: This is the first study to establish a standardized ultrasound
      protocol as an adjunct diagnostic tool to clinical examination for the dynamic
      evaluation of postoperative hernia and abdominal wall laxity.

PMID- 16582774
TI  - Endoscopic forehead rejuvenation: I. Limitations, flaws, and rewards.
AB  - BACKGROUND: The efficacy of endoscopic forehead rejuvenation has been questioned.
      However, many proponents of the technique are convinced that this procedure is
      indeed an optimal choice for the majority of patients desiring forehead
      rejuvenation and have found the means of preventing adversities. METHODS: The
      purpose of this article is to discuss the common features and reasons for
      suboptimal endoscopic forehead rejuvenation outcomes and avoidance of these flaws
      based on the author's experience with 372 procedures. RESULTS: These
      imperfections include inadequate muscle resection, under- or overelevation of the
      eyebrows, asymmetry, glabellar dimpling or depression, displeasing eyebrow arch,
      and excessive separation of the eyebrows. CONCLUSIONS: In this report, the
      details of these flawed outcomes are discussed, and the ways in which they can be
      avoided or corrected are reviewed to improve the learning curve for less
      experienced surgeons and to aid in producing more predictable and pleasing
      results.

PMID- 16582776
TI  - Endoscopic forehead rejuvenation: II. Long-term results.
AB  - BACKGROUND: The purpose of this study was to analyze the long-term objective and
      subjective outcomes in patients who have undergone endoscopic forehead
      rejuvenation. METHODS: Preoperative and postoperative photographs of 100 patients
      who underwent endoscopic forehead rejuvenation by one surgeon (B.G.) between 1993
      and 2001 were objectively analyzed. Postoperative changes in left and right
      eyebrow position were assessed in each patient by counting the number of pixels
      in the digitalized photographs and by clinical measurements, and compared with
      preoperative values. In addition, subjective ratings of the surgical outcome
      obtained from both the patient and the evaluating surgeon were compared. All data
      were analyzed using the paired t test. RESULTS: The average postoperative follow
      up was 44 months (range, 12 to 95 months). Statistically significant differences
      in brow position between the preoperative and postoperative periods were observed
      in the following categories: the average distance from the lower brow margin to
      the upper eyelid margin (p < 0.005), the average distance from the lateral brow
      margin to the medial canthus horizontal line (p < 0.001), elevation of the
      lateral canthus relative to the medial canthus (p < 0.001), and the distance
      between the medial margins of the eyebrows (p < 0.001). In addition,
      preoperatively, 74 percent of eyebrows were positioned below the superior orbital
      rim, whereas 97 percent were positioned at the rim or above postoperatively, with
      82 percent positioned above the rim. The most common complications were some
      degree of persistent paresthesia (50 percent), itching (14 percent), and forehead
      dynamic imperfections and irregularity (10 percent). CONCLUSION: Endoscopic
      forehead rejuvenation improves brow position relative to the orbital rim, brow
      arch form, vertical frown lines, and horizontal frown lines of the forehead, with
      stable results many years after surgery.

PMID- 16582778
TI  - Hernia repair and abdominoplasty in gastric bypass patients.
AB  - BACKGROUND: Patients who sustain massive weight loss after open gastric bypass
      surgery are prone to incisional hernias. The authors undertook a retrospective
      study with two objectives: to characterize this patient population at their
      institution and to review their experience with treatment of incisional hernias
      in massive weight loss patients who had open gastric bypass surgery. With
      increasing prevalence of such patients, the authors aim to improve understanding
      and treatment of this disease entity and thereby improve patient outcomes.
      METHODS: Operating room records and the patient database of the primary plastic
      surgeon treating massive weight loss patients at an academic teaching institution
      were retrospectively reviewed. Incisional hernia was often diagnosed before
      surgery but confirmed intraoperatively. Surgical management included primary
      repair of the hernia with plication of the abdominal wall from xiphoid to pubis
      and removal of redundant abdominal skin. RESULTS: From February of 2001 to
      December of 2003, 40 patients had hernia repair in combination with
      abdominoplasty. Average age was 42 years, and average weight loss was 152 pounds.
      Average body mass index at the time of plastic surgery was 35.6. Average
      abdominal skin resection was 9.9 pounds. Hernia recurred in one patient with a
      body mass index of 41.3 after heavy lifting within 1 year of hernia repair
      surgery. Other complications included wound-healing problems (20 percent); seroma
      (12.5 percent); bleeding requiring surgical take-back (2.5 percent); suture
      abscess requiring surgical removal of suture (7.5 percent); bleeding anastomotic
      ulcer requiring transfusion (2.5 percent); and fatal pulmonary embolus (2.5
      percent). Of the group, 60 percent had uncomplicated healing. CONCLUSIONS:
      Hernias are safely and preferentially repaired at the time of removal of
      redundant abdominal panniculus after massive weight loss sustained from gastric
      bypass surgery. The authors present their approach to hernia repair and
      abdominoplasty in this patient group, with acceptable results.

PMID- 16582780
TI  - Anatomical localization of the umbilicus: an Indian study.
AB  - BACKGROUND: The umbilicus is essential to the aesthetic appearance of the
      abdomen. However, very little has been written about the exact location of the
      aesthetically pleasing umbilicus as far as the Indian cosmopolitan population is
      concerned. Although a variety of reconstructive methods are available, no real
      standards define the location of the umbilicus. METHODS: In this study, 75
      cosmopolitan female volunteers were evaluated in supine position, and the
      distance of the umbilicus (from central stalk) to fixed bony points over the
      anterior abdominal wall was measured. These linear measurements were subjected to
      standard statistical methods. RESULTS: In this study, the authors observed that
      the umbilicus is situated around the midline plane such that the ratio of the
      distance between the xiphisternum and the umbilicus and the distance between the
      pubic symphysis and the umbilicus is 1.6:1; also, the ratio of the distance
      between the umbilicus and anterior superior iliac spine and the inter-anterior
      superior iliac spine is approximately 0.6:1. CONCLUSIONS: During umbilicoplasty,
      when each anterior superior iliac spine is taken as a center, and arcs are drawn
      with a radius 0.6 times that of the inter-anterior superior iliac spine distance,
      the point of intersection of these arcs is the approximate location of the
      umbilicus around the midline plane, which should match the ratio of 1.6:1 (i.e.,
      the ratio of the distance from the umbilicus to the xiphisternum and the distance
      from umbilicus to the pubic symphysis). An effort is made to find and establish
      the body proportions and symmetry and to determine the critical ratios so as to
      help the reconstructive surgeon to plan an aesthetically pleasing umbilicus.

PMID- 16582781
TI  - When an adult female seeks ritual genital alteration: ethics, law, and the
      parameters of participation.
AB  - Ritual genital cutting for women, a common practice in Africa and elsewhere
      around the world, remains dangerous and controversial. In recent years, a 14-year
      old girl living in Sierra Leone exsanguinated and died following a ritualistic
      genital cutting. Hoping to avoid that fate, women with backgrounds that accept
      ritual genital cutting may, when they reach majority age, ask plastic surgeons to
      perform genital alterations for cultural reasons. Although plastic surgeons
      routinely perform cosmetic procedures, unique ethical and legal concerns arise
      when an adult female patient asks a surgeon to spare her the tribal elder's knife
      and alter her genitalia according to tradition and custom. Misinformation and
      confusion about this issue exist. This article explores the ethical and legal
      issues relevant to this situation and explains how the thoughtful surgeon should
      proceed.

PMID- 16582783
TI  - Vacuum-assisted closure of the sternotomy wound: respiratory mechanics and
      ventilation.
AB  - BACKGROUND: Numerous authors have reported promising results with the use of
      vacuum-assisted closure therapy in poststernotomy mediastinitis. The negative
      pressure applied to the anterior mediastinum substantially exceeds the normal
      negative pressure in the pleural cavities, and interaction with respiratory
      physiology cannot be excluded. The aim of the present study was to evaluate
      whether the application of six clinically relevant negative pressures between -50
      mmHg and -175 mmHg to the sternotomy wound affects respiratory parameters in a
      porcine model. METHODS: A midline sternotomy was performed in six mechanically
      ventilated pigs weighing 70 +/- 3 kg. Vacuum-assisted closure therapy was applied
      with continuous negative pressure in a randomized order to the sternotomy wound.
      The following respiratory parameters were monitored by a carbon dioxide-based
      noninvasive monitoring system connected to the ventilator: carbon dioxide
      elimination, peak inspiratory pressure, peak expiratory flow, alveolar minute
      volume, alveolar tidal volume, expired tidal volume, static compliance, and
      airway resistance. RESULTS: All pigs survived the treatment, and there was no
      significant change in the respiratory parameters investigated at any of the six
      negative pressures applied. A tendency toward increased airway resistance was
      noted when -175 mmHg was applied, although this change was not significant.
      CONCLUSIONS: The application of negative pressure therapy in the treatment of
      deep poststernotomy infections is a novel modality gaining increased attention.
      In this study, no impairment in respiratory mechanics, ventilation, or
      oxygenation was detected when comparing applied pressures ranging from -50 mmHg
      to -175 mmHg in the sternotomy wound.

PMID- 16582784
TI  - Guided tissue regeneration enhances bone formation in a rat model of failed
      osteogenesis.
AB  - BACKGROUND: Guided tissue regeneration is a technique that uses barrier materials
      to enhance tissue regeneration. Although previously demonstrated to be an
      effective way of enhancing craniofacial osteogenesis in several animal models,
      the ability of guided tissue regeneration to augment bone formation in the
      context of distraction osteogenesis is unknown. In the current study, the authors
      applied the principle of guided tissue regeneration to their rat mandibular
      distraction osteogenesis model in an attempt to enhance bone regeneration.
      METHODS: Twelve (n = 6 per group) adult Sprague-Dawley rats underwent routine
      gradual distraction (5 days' latency, 4-mm distraction over 8 days, 4 to 6 weeks
      of consolidation) and acute distraction (immediate lengthening to 4 mm, 6 to 8
      weeks of consolidation). An additional 10 animals underwent acute distraction
      followed by application of bioabsorbable Gore Resolut XT membranes (acute
      distraction plus guided tissue regeneration). Membranes were completely wrapped
      around the distraction gap. Animals were killed 6 and 8 weeks postoperatively and
      mandibles analyzed radiographically and histologically. RESULTS: Quantitative
      histomorphometric analyses were performed to compare relative bone formation
      between all three groups. Gradual distraction mandibles achieved bony union by 6
      weeks with 86 percent bone formation, which increased to 98 percent by 8 weeks.
      Acute distraction mandibles healed with a fibrous nonunion and only 37 percent
      bone formation by 8 weeks. In contrast, acute distraction plus guided tissue
      regeneration-treated mandibles formed significantly more bone than acute
      distraction mandibles by 6 weeks (57 percent) and achieved bony bridging by 8
      weeks, with 88 percent new bone formation. CONCLUSION: The authors' data
      demonstrate that guided tissue regeneration can significantly enhance bone
      formation in a fibrous nonunion model of mandibular distraction osteogenesis.

PMID- 16582785
TI  - Use of calcium phosphate cement paste in orbital volume augmentation.
AB  - BACKGROUND: The development of calcium phosphate in cement paste form has made
      its application simplified and easy. In this study, the authors used an alpha
      tricalcium phosphate/dicalcium phosphate dibasic/tetracalcium phosphate
      monoxide/hydroxyapatite injectable calcium phosphate cement paste to evaluate its
      potential use in orbital volume augmentation. METHODS: Five New Zealand white
      rabbits were used in this study. In each rabbit, the right orbit was directly
      implanted with calcium phosphate cement in its injectable paste form, and a
      prehardened form was placed in the left orbit. The orbital roof was approached
      through a subciliary skin incision and the implant was placed posterior to the
      globe of the eyeball to push it outward. Measurement of proptosis and intraocular
      pressure was monitored before and after implantation. The animals were killed
      after 3 months, and orbit bone-implant samples were taken for histology and
      microradiography. RESULTS: In both groups, proptosis was induced, 4.2 +/- 0.27 mm
      in the prehardened group and 3.8 +/- 0.22 mm in the injectable group. These
      values taken 1 week postimplantation were unchanged until the end of the
      experiment and were maintained without significant intraocular pressure changes.
      The implants were well tolerated, and no sign of infection, extrusion, or
      migration was noted. Histologic analysis showed good biocompatibility and
      osteoconductivity, and microradiography has confirmed a well-set cement with
      direct bone union to it. CONCLUSION: These findings therefore indicate that
      calcium phosphate cement implant, when used as an injectable paste or in its
      prehardened form, can be a safe, effective material for orbital volume
      augmentation.

PMID- 16582786
TI  - Regenerating axons emerge far proximal to the coaptation site in end-to-side
      nerve coaptation without a perineurial window using a T-shaped chamber.
AB  - BACKGROUND: Considerable controversy exists concerning the mechanism of axonal
      regeneration in end-to-side neurorrhaphy. The authors studied the mode of axonal
      regeneration in end-to-side neurorrhaphy without a perineurial window using a rat
      sciatic nerve model. METHODS: Twenty-seven rats were used. A 10-mm segment of
      peroneal nerve was harvested and coapted to the ipsilateral tibial nerve in end
      to-side fashion using a T-shaped silicone chamber to minimize the tibial nerve
      damaged by surgery. To explain the role of nerve damage on axonal regeneration in
      end-to-side neurorrhaphy, we also used an isogenic nerve transplantation model in
      which the peroneal nerve remained intact. The mode of axonal regeneration was
      studied with electron microscopy, morphometric analysis, immunofluorescence, and
      immunohistochemistry. RESULTS: Both morphometric analysis and immunolabeling of
      neurofilaments demonstrated that regenerating axons emerge at sites far proximal
      to the coaptation site, travel within the tibial nerve, traverse the perineurium
      circumferentially around the coaptation site, and then invade into the peroneal
      nerve. Electron microscopy and a double-labeled immunofluorescence study with
      antibodies against neurofilament and tenascin-C confirmed large-scale axonal
      penetration into the perineurium around the coaptation site. Immunofluorescence
      with antibody against NG2, a marker of axonal regeneration, prevented the
      possibility of collateral sprouting at the coaptation site. In addition, an end
      to-side neurorrhaphy model with an isogenic peroneal nerve clearly demonstrated
      that nerve damage is a prerequisite for axonal regeneration through end-to-side
      neurorrhaphy. CONCLUSIONS: The authors could not locate the site of axonal
      sprouting in end-to-side neurorrhaphy without a perineurial window; however, this
      study cast doubts on current hypothesis on the mode of axonal regeneration in end
      to-side neurorrhaphy.

PMID- 16582788
TI  - Plasma free hemoglobin: a novel diagnostic test for assessment of the depth of
      burn injury.
AB  - BACKGROUND: Accurate determination of the depth of burn injury is difficult, even
      for experienced surgeons. The authors hypothesized that the level of plasma free
      hemoglobin following burn injury is correlated to the depth of burn injury, and
      they evaluated this hypothesis in a murine model. METHODS: Full-thickness and
      partial-thickness burn injuries of varying sizes were inflicted on 38 and 36 male
      Wistar rats, respectively. Blood specimens were taken at 0, 15, 30, 45, and 60
      minutes after burn injury, and the levels of plasma free hemoglobin were
      determined spectrophotometrically. RESULTS: Full-thickness burns cause two times
      more hemolysis than partial-thickness burns (p < 0.05). A linear correlation was
      demonstrated between plasma free hemoglobin levels and total body surface area
      burned in both the full-thickness (r = 0.91, p < 0.001) and partial-thickness
      burn groups (r = 0.94, p < 0.001). The correlation between the quantity of
      hemolysis and the total body surface area burned was strongest at 15 minutes
      after the onset of burn injury. The levels of free hemoglobin peaked rapidly
      between 15 and 30 minutes after thermal injury and declined thereafter.
      CONCLUSIONS: The authors' data suggest that the level of plasma free hemoglobin
      after burn injury is related to the size and depth of burn injury. This test can
      potentially be a valuable diagnostic adjunct in the assessment of burns.

PMID- 16582789
TI  - A rabbit model for capsular contracture: development and clinical implications.
AB  - BACKGROUND: Capsular contracture remains one of the most common complications
      involving aesthetic and reconstructive breast surgery; however, its cause,
      prevention, and treatment remain to be fully elucidated. Presently, there is no
      accurate and reproducible pathologic in vitro or in vivo model examining capsular
      contracture. The purpose of this study was to establish an effective pathologic
      capsular contracture animal model that mimics the formation of capsular
      contracture response in humans. METHODS: New Zealand White rabbits (n = 32) were
      subdivided into experimental (n = 16) and control groups (n = 16). Each subgroup
      underwent placement of smooth saline mini implants (30 cc) beneath the panniculus
      carnosus in the dorsal region of the back. In addition, the experimental group
      underwent instillation of fibrin glue into the implant pocket as a capsular
      contracture-inducing agent. Rabbits were euthanized from 2 to 8 weeks after the
      procedure. Before the animals were euthanized, each implant was serially inflated
      with saline and a pressure-volume curve was developed using a Stryker device to
      assess the degree of contracture. Representative capsule samples were collected
      and histologically examined. Normal and contracted human capsular tissue samples
      were also collected from patients undergoing breast implant revision and
      replacement procedures. Tissue samples were assessed histologically. RESULTS:
      Pressure-volume curves demonstrated a statistically significantly increased
      intracapsular pressure in the experimental group compared with the control group.
      The experimental subgroup had thicker, less transparent capsules than the control
      group. Histologic evaluation of the rabbit capsule was similar to that of the
      human capsule for the control and experimental subgroups. CONCLUSIONS: The
      authors conclude that pathologic capsular contracture can be reliably induced in
      the rabbit. This animal model provides the framework for future investigations
      testing the effects of various systemic or local agents on reduction of capsular
      contracture.

PMID- 16582791
TI  - A cost/utility analysis of open reduction and internal fixation versus cast
      immobilization for acute nondisplaced mid-waist scaphoid fractures.
AB  - BACKGROUND: Open reduction and internal fixation and cast immobilization are both
      acceptable treatment options for nondisplaced waist fractures of the scaphoid.
      The authors conducted a cost/utility analysis to weigh open reduction and
      internal fixation against cast immobilization in the treatment of acute
      nondisplaced mid-waist scaphoid fractures. METHODS: The authors used a decision
      analytic model to calculate the outcomes and costs of open reduction and internal
      fixation and cast immobilization, assuming the societal perspective. Utilities
      were assessed from 50 randomly selected medical students using the time trade-off
      method. Outcome probabilities taken from the literature were factored into the
      calculation of quality-adjusted life-years associated with each treatment. The
      authors estimated medical costs using Medicare reimbursement rates, and costs of
      lost productivity were estimated by average wages obtained from the U.S. Bureau
      of Labor Statistics. RESULTS: Open reduction and internal fixation offers greater
      quality-adjusted life-years compared with casting, with an increase ranging from
      0.21 quality-adjusted life-years for the 25- to 34-year age group to 0.04 quality
      adjusted life-years for the > or =65-year age group. Open reduction and internal
      fixation is less costly than casting ($7940 versus $13,851 per patient) because
      of a longer period of lost productivity with casting. Open reduction and internal
      fixation is therefore the dominant strategy. When considering only direct costs,
      the incremental cost/utility ratio for open reduction and internal fixation
      ranges from $5438 per quality-adjusted life-year for the 25- to 34-year age group
      to $11,420 for the 55- to 64-year age group, and $29,850 for the > or =65-year
      age group. CONCLUSIONS: Compared with casting, open reduction and internal
      fixation is cost saving from the societal perspective ($5911 less per patient).
      When considering only direct costs, open reduction and internal fixation is cost
      effective relative to other widely accepted interventions.

PMID- 16582793
TI  - A technique for the repair of chronic volar plate avulsion of the proximal
      interphalangeal joint: a review of 54 cases.
AB  - BACKGROUND: The authors delineate a subgroup of proximal interphalangeal joint
      injuries with chronic pain and limitation of movement, despite a stable joint,
      and describe and evaluate a surgical procedure. METHODS: Through a volar
      approach, the volar plate is freed from scar but remains connected on either the
      ulnar or radial border. A new connection to the middle phalanx is established by
      creating a bony groove, and the volar plate is loosely attached distally. Fifty
      four joints with chronic volar plate avulsion injuries of the proximal
      interphalangeal joint were evaluated. All patients had chronic pain and
      limitation of motion and function in a stable and congruent joint. Patients were
      examined at 6 weeks, 3 months, and 1 year after surgery. Range of motion, grip
      strength, and pain were evaluated. The average time to surgery was 10.5 +/- 11.8
      months (range, 2 to 65.4 months). The mean postoperative follow-up period was
      10.0 +/- 12.8 months (range, 3 to 73.5 months). RESULTS: All patients had an
      improved range of motion following surgery. The difference from the preoperative
      range of motion was statistically significant (p < 0.0001). None of the patients
      reported pain on rest after surgery, and five patients reported activity pain.
      The mean grip strength was 32.4 +/- 13.4 kg for hand that had been operated on
      and 41.0 +/- 14 kg for the hand that had not been operated on. CONCLUSIONS: This
      technique for repair of chronic volar plate avulsion injuries allows early motion
      and results in significant improvement in range of motion, pain, and overall
      function in this subgroup of patients.

PMID- 16582796
TI  - Flexor sheath irrigation collection system: the way we do it.

PMID- 16582795
TI  - Increased metabolic activity of fibroblasts derived from cords compared with
      nodule fibroblasts sampling from patients with Dupuytren's contracture.
AB  - BACKGROUND: The pathogenesis of Dupuytren's contracture is characterized by
      progress in several stages. The disease process includes two structurally
      distinct fibrotic elements, the so-called nodule and the cord. Several hypotheses
      have been proposed regarding the cause. Until now, there has been ongoing
      discussion regarding whether cords or nodules are the primary source of the
      disease. METHODS: Tissues from 24 patients with Dupuytren's disease were obtained
      during hand surgery, providing samples from nodules and cords for cell culture.
      Tissue from the flexor retinaculum excised from healthy patients during surgical
      procedures on the hand served as control. By using the explant culture technique,
      fibroblasts were isolated and grown in standard medium. Besides morphological
      analysis, XTT proliferation tests were performed at various time periods to
      measure the metabolic activity of the cultivated fibroblasts. RESULTS:
      Statistical analysis revealed significant differences of nodule- and cord-derived
      fibroblasts after 1 hour (p = 0.0150), 8 hours (p < 0.0001), and 16 hours (p <
      0.0001). CONCLUSIONS: The authors suggest that distinct proliferative properties
      of Dupuytren-derived fibroblasts are dependent on the cells' origin. Conclusions
      about the cause or pathogenesis cannot yet be drawn. Further investigation
      concerning their apparently different fibroproliferative properties is necessary.

PMID- 16582797
TI  - Le Fort III osteotomy or distraction osteogenesis imperfecta: your choice.
AB  - BACKGROUND: Traditional Le Fort III osteotomies have been described by several
      authors; however, few have reported the distances advanced and stability over
      time. METHODS: The authors assessed their last 30 Le Fort III osteotomies with
      respect to the immediate incisor advancement achieved at surgery and long-term
      advancement as measured at the A-point from preoperative and postoperative
      cephalometric tracings. The authors then compared their results with those in the
      literature for Le Fort III distraction techniques. Comparisons were made with
      respect to distraction distance maintained, the need for bone grafting, airway
      results, morbidity, and cost. RESULTS: The mean incisor advancement at the time
      of surgery as recorded in 14 patients was 21.6 mm (range, 12 to 28 mm). The long
      term cephalometric A-point measurements in 14 patients demonstrated a mean of
      14.14 mm (range, 8 to 25 mm). CONCLUSION: The authors conclude that, at the
      present time, no significant improvement in the results using Le Fort III
      distraction osteogenesis when compared with traditional methods has been shown.

PMID- 16582798
TI  - Radiofrequency in the treatment of craniofacial plexiform neurofibromatosis: a
      pilot study.
AB  - BACKGROUND: Neurofibromatosis type 1 manifests itself by the development of
      plexiform neurofibromas, with craniofacial deformities caused by bone alterations
      and soft-tissue infiltration. The medical treatment of this disease is
      disappointing, and the surgical management of these deformities calls for
      aggressive procedures. There is a strong risk of recurrence. METHODS: A pilot
      study was performed to test radiofrequency as a minimally invasive method with
      which to diminish the size of craniofacial neurofibromas either as an adjunct to
      craniofacial surgery (in cranio-orbital neurofibromas) or to avoid a visible scar
      in young patients (in infraorbital neurofibromas). Five patients ranging in age
      from 6 to 18 years were treated by three procedures 2 months apart using
      radiofrequency performed under local anesthesia or under sedation for the
      youngest patients. RESULTS: The tolerance of the treatment was excellent, with no
      major side effects and no pain in the postoperative course. A diminution of the
      size of the lesion was noted clinically in four patients and on computed
      tomography in two patients. A biopsy performed in one case illustrated the effect
      of the treatment. CONCLUSIONS: A partial diminution or stabilization of plexiform
      neurofibromas may be obtained using radiofrequency. This treatment is well
      tolerated. The best effect can be observed in the early stages of the disease.
      The optimal dose and frequency of the procedure require further study.

PMID- 16582799
TI  - Repair of traumatic orbital wall defects using conchal cartilage.
AB  - BACKGROUND: The authors' aim was to investigate the efficiency of conchal
      cartilage grafts in defective orbital wall fractures, which are encountered
      isolated or in combination with other orbitozygomatic fractures. The authors
      assessed, for this purpose, the follow-up results of patients treated by using
      conchal cartilage grafts. METHODS: Ten patients who had defective orbital wall
      fractures and were treated by using conchal cartilage graft among those treated
      for facial fractures in the authors' clinic were included in the study. The wall
      defects in the patients were detected either with preoperative radiologic images
      or with orbital exploration performed to look for a possible defect accompanying
      the fracture with orbital extension during the operation. In all patients (four
      isolated and six combined orbital fractures), who had defects varying from 100 to
      400 mm, conchal cartilage grafts were adapted to the defect. In the postoperative
      follow-up, Hertel exophthalmometry was also performed together with clinical
      examination so that enophthalmos that might develop as a complication could be
      assessed. RESULTS: In the postoperative period, cartilage graft was palpated
      slightly in two patients at the edge of the infraorbital rim. Limitation in eye
      movement, diplopia, and enophthalmos did not occur in our patients, except for
      one who reported to us 1 year after the primary trauma. No complication in the
      donor area was observed. CONCLUSIONS: Conchal cartilage could be considered one
      of the autogenous materials among those materials suitable for the repair of
      defective orbital wall fractures that are not oversized. It has the advantages of
      being adequate for reconstruction of the fracture, easy to obtain, easily
      adaptable to the orbital walls, and having minimum morbidity at the donor site.

PMID- 16582800
TI  - The free serratus anterior flap and its cutaneous component for reconstruction of
      the face: a series of 27 cases.
AB  - BACKGROUND: The serratus anterior flap is commonly used without its cutaneous
      component and is covered with a skin graft. The authors have successfully used
      the free serratus anterior flap along with its skin paddle and have found it to
      be valuable for reconstruction of the face. METHODS: Fresh cadaveric dissections
      and arteriography were performed to identify perforator vessels to the skin
      overlying the muscle. Clinically, free transfer of the musculocutaneous flap to
      the face was carried out in 27 patients, mostly for severe noma (infection)
      sequelae. RESULTS: Anatomical dissection and arteriography revealed no cutaneous
      perforator vessels directly communicating with the vascular pedicle of the
      muscle. However, large perforators from the intercostal vessels were found
      passing through the muscle to reach the skin. In the clinical cases, flap
      survival was 100 percent in 24 patients. CONCLUSIONS: The serratus anterior
      musculocutaneous flap is reliable and particularly well-suited for reconstruction
      of the face, and has many advantages. The authors speculate that the skin paddle
      may be vascularized by perforators from the intercostal vessels communicating
      with the thoracodorsal pedicle through intramuscular choke vessels.

PMID- 16582801
TI  - Lateral canthopexy using the hollow needle technique.

PMID- 16582802
TI  - Combined tissue expansion and prelamination of forearm flap in major ear
      reconstruction.

PMID- 16582803
TI  - Hospital volume outcome and discharge disposition of burn patients.
AB  - BACKGROUND: The purpose of this investigation was to determine the impact of
      hospital clinical volume on patient outcomes (i.e., in-hospital mortality, length
      of stay) and discharge disposition of burn patients using a large nationally
      representative database. METHODS: Patient data were obtained from the 1999-2001
      National Inpatient Sample using burn diagnosis-related group codes 504 through
      511. Hospitals were segregated into high-volume hospitals (treating more than 100
      patients per year), medium-volume hospitals (treating 20 to 99 patients per
      year), and low-volume hospitals (treating fewer than 20 patients per year).
      Mortality, length of stay, and discharge disposition were catalogued for each
      diagnosis-related group code and hospital type. RESULTS: In diagnosis-related
      group pair 504/505 (most severe), the mortality rate in patients admitted to high
      volume hospitals (33.5 percent) was significantly higher than in patients
      admitted to both medium-volume hospitals (28.8 percent) and low-volume hospitals
      (11.5 percent) (p = 0.002). Within lower severity diagnosis-related groups, where
      the mortality rate was lower across all admissions, medium-volume hospitals and
      high-volume hospitals had a higher proportion of routine discharges to home, a
      lower need for home care, and a lower proportion of transfers compared with low
      volume hospitals. Despite shorter length of stay, across most burn diagnosis
      related groups, patients admitted to low-volume hospitals had lower rates of
      routine discharges and a higher proportion of admissions "with complications."
      CONCLUSION: Higher-volume facilities, despite receiving the most severe burn
      patients, may provide better patient outcomes than lower-volume facilities. The
      patterns of discharges found at lower-volume facilities may result in higher
      diagnosis-related group reimbursement "capture" by lower-volume facilities and
      higher postdischarge resource use.

PMID- 16582805
TI  - Use of the medial side of the knee skin as a free flap: saphenous flap.
AB  - BACKGROUND: The knee region is a good free skin flap donor site, as it has
      minimal subcutaneous tissue and provides a hidden donor site. Acland et al. first
      used the skin over the medial side of the knee as a "saphenous flap" based on the
      saphenous branch of the descending genicular artery. METHODS: The authors studied
      the descending genicular artery and its saphenous branch in six cadaver limbs and
      elevated the skin over the medial side of the knee as a free flap in six patients
      to reconstruct lower extremity defects. RESULTS: In all clinical cases, the
      authors were able to elevate a skin flap from the skin on the medial side of the
      knee. The saphenous branch was absent in one cadaveric limb and one patient limb;
      instead, a direct cutaneous branch from the femoral artery reached the skin and
      had nearly the same caliber as the saphenous branch of the other cases. All the
      flaps survived and the defects healed well. CONCLUSION: The medial side of the
      knee is a good donor site, as it provides thin skin with innervation potential by
      means of the medial femoral cutaneous nerve and leaves an inconspicuous donor
      site scar.

PMID- 16582806
TI  - Lower extremity trauma: trends in the management of soft-tissue reconstruction of
      open tibia-fibula fractures.
AB  - BACKGROUND: Open lower leg fractures with exposed bone or tendon continue to be
      challenging for plastic surgeons. Microvascular free-tissue transfer increases
      the ability to close wounds, transfer vascularized bone, and prevent amputation,
      yet remains a complex, invasive procedure with significant complication rates,
      donor-site morbidity, and failure rates. This review documents the changing
      treatment protocol in the authors' institution for these injuries. METHODS: Two
      hundred ninety consecutive open tibia-fibula fractures over a 12-year period
      (1992 to 2003) were retrospectively reviewed and methods and outcomes were
      compared by grouping the fractures into 4-year intervals. RESULTS: The number of
      open lower extremity fractures increased, whereas the distribution of Gustilo
      grade I to III fractures remained unchanged. Overall, free-tissue transfer was
      performed less frequently and constituted 20 percent of reconstructions in period
      1 (1992 to 1995), 11 percent in period 2 (1996 to 1999), and 5 percent in period
      3 (2000 to 2003). For the most severe fractures, Gustilo grade III, free-flap
      reconstruction has decreased significantly, constituting 42 percent, 26 percent,
      and 11 percent of procedures in periods 1, 2, and 3, respectively. Local flaps
      for grade III fractures have remained relatively constant throughout the study.
      In contrast, local wound care for grade III fractures, including skin grafts,
      delayed primary closures, and secondary intention closures has significantly
      increased from 22 percent to 49 percent of reconstructions from periods 1 through
      3. In 1997, the authors began to use the vacuum-assisted closure device and now
      use it in nearly half of all open fractures. Despite this trend, there has been
      no change in infection, amputation, or malunion/nonunion rates and a decrease in
      reoperation rate with at least 1-year follow-up. CONCLUSIONS: These results
      demonstrate a change in practice, with a trend down the reconstructive ladder,
      currently using fewer free flaps and more delayed closures and skin grafts with
      frequent use of the vacuum-assisted closure sponge. Possible reasons for this
      change are a better understanding of lower leg vascular anatomy and better use of
      improved wound care technology.

PMID- 16582808
TI  - The role of muscle flaps in wound salvage after vascular graft infections: the
      Emory experience.
AB  - BACKGROUND: The incidence of prosthetic graft infection is 1 to 6 percent, and
      the mortality rate of infected aortoiliac or aortofemoral bypass is 25 to 75
      percent. The goal of this study was to report the use of muscle flaps in the
      management of patients presenting with infected vascular grafts. METHODS: A total
      of 22 patients required 26 muscle flaps to cover 24 infected vascular grafts.
      Muscle flaps were used for local wound control in all patients regardless of the
      fate of the graft. The vascular surgeons elected for graft salvage in eight of
      the 24 grafts. All of the muscle flaps survived. RESULTS: The average time
      interval between the bypass and infection was 371 days. One-month follow-up
      revealed an 88 percent salvage rate, but this decreased to 50 percent during the
      mean follow-up of 23 months. None of the patients originally managed with a
      salvaged graft lost a limb, and overall, 14 of 22 limbs in this series remained
      viable (64.0 percent). The mortality rate during the index hospitalization was 9
      percent. In this series, suprainguinal grafts had a higher mortality rate. In
      addition, infection occurring more than 1 month postoperatively, culture-positive
      Pseudomonas and methicillin-resistant species, and exposure of the arterial-graft
      anastomosis were poor prognostic indicators of graft preservation. CONCLUSIONS:
      Management of infected vascular grafts remains a challenging problem. Muscle flap
      coverage should have a high priority, as the chance of a good outcome is highly
      favorable in early infections.

PMID- 16582809
TI  - Creativity from within.

PMID- 16582810
TI  - A plea for understanding and logical thinking.

PMID- 16582814
TI  - Correction of ectropion in facial paralysis.

PMID- 16582815
TI  - Correction of ectropion in facial paralysis.

PMID- 16582819
TI  - Successful soft-tissue coverage of a tibial wound in the distal third of the leg.

PMID- 16582820
TI  - Botulinum treatment of forehead wrinkles.

PMID- 16582822
TI  - Is surgery always necessary in the treatment of aplasia cutis congenita?

PMID- 16582821
TI  - Elevation of the umbilicus with skin hooks aids excision in abdominoplasty.

PMID- 16582824
TI  - Facial injury of infant by domestic pig bite: neglect, ignorance, or house
      designs defect?

PMID- 16582825
TI  - Posttraumatic lipoma in a patient with congenital factor X deficiency.

PMID- 16582826
TI  - Decongestant sympathomimetic drugs sold "over the counter" can produce skin
      slough of face lift flaps.

PMID- 16582827
TI  - A little trick to reduce pain at the moment of blepharoplasty stitch removal.

PMID- 16582828
TI  - Steal syndrome of the hand complicating an arteriovenous fistula.

PMID- 16582829
TI  - Unusually successive deflation of textured-surface breast implants.

PMID- 16582830
TI  - Microvascular anastomosis timing in digital replantations.

PMID- 16582832
TI  - Use of distally based cross-leg sural artery flap and cadaveric Achilles tendon
      graft in the reconstruction of a combined defect of the Achilles tendon and
      overlying soft tissue.

PMID- 16582831
TI  - Occam's razor revisited: potential hazards of multiple pathology.

PMID- 16582833
TI  - Calciphylaxis in a patient with chronic diabetic renal failure but normal
      parathormone.

PMID- 16582834
TI  - Plaster cast or three-dimensional computer imaging: which is better?

PMID- 16582835
TI  - Ubiquitous equipment on a plastic surgery ward: an infection risk?

PMID- 16582836
TI  - Visual documentation of oral consent: a new method of informed consent before
      major gigantomastia reduction for an illiterate population.

PMID- 16582838
TI  - Spinal decompensation in neuromuscular disease.
AB  - STUDY DESIGN: In this retrospective radiography study, we analyzed curve shape
      and direction in scoliosis secondary to neuromuscular disease. OBJECTIVE: To
      determine if in different types of neuromuscular scoliosis a predominant curve
      pattern can be found and if similarities with idiopathic scoliosis exist. SUMMARY
      OF BACKGROUND DATA: To the authors' knowledge, systematic analysis of curve
      patterns in patients with neuromuscular scoliosis has not been performed in a
      group of this size and composition. METHODS: Spinal full-length radiographs of
      198 patients with neuromuscular scoliosis were analyzed for curve shape and
      direction. Patients were divided into 4 groups consisting of Duchenne muscular
      dystrophy, cerebral palsy, spinal muscular atrophy, and spina bifida. RESULTS:
      The results of this study show a predominance of right-sided thoracic and
      thoracolumbar curves, and left-sided lumbar curves, which differed significantly
      from an equal right-left distribution. Apical levels were respectively at T8,
      T12/L1 disc, and L2. CONCLUSION: In neuromuscular scoliosis, curve patterns and
      apical levels are similar to what is seen in the most prevalent types of
      adolescent idiopathic scoliosis.

PMID- 16582839
TI  - Spine and rib abnormalities and stature in spondylocostal dysostosis.
AB  - STUDY DESIGN: A retrospective study of radiographic and clinical findings of
      spondylocostal dysostosis. OBJECTIVE: To determine the features of spondylocostal
      dysostosis diagnosed using consistent diagnostic criteria. SUMMARY OF BACKGROUND
      DATA: To our knowledge, no clear definition of spondylocostal dysostosis exists,
      and little information is available regarding its clinical or radiographic
      features. METHODS: We defined spondylocostal dysostosis as a congenital spinal
      disorder consisting of >or=2 vertebral anomalies associated with rib anomalies,
      without crab-like chest. For 30 patients, including 12 males and 18 females, who
      met these criteria, we evaluated vertebral and rib anomalies, birth and present
      body height, and associated anomalies. There were only 2 familial cases. RESULTS:
      Features of spondylocostal dysostosis were: (1) anomalies involved the thoracic
      region in all cases; many also involved the cervical spine; (2) most patients had
      >or=4 vertebral anomalies; (3) frequent vertebral anomalies were butterfly
      vertebra, hemivertebra, complete block, and unilateral bar, which were associated
      with both rib absence and fusion; (4) short stature was not always present at
      birth; and (5) complete block was 1 factor identified as being related to short
      stature after 12 years of age. CONCLUSION: Several features of sporadic
      spondylocostal dysostosis disorder were determined, including new findings
      related to body height.

PMID- 16582840
TI  - Effect of the increase in the height of lumbar disc space on facet joint
      articulation area in sagittal plane.
AB  - STUDY DESIGN: Computerized tomography (CT) of the lumbar spine cadaveric
      specimens was used to evaluate the effect of increasing the height of the disc
      space in the lumbar spine to the facet joint articulation in the sagittal plane.
      OBJECTIVE: To show how the facet joint articulation is affected by increasing the
      height of the disc space in the lumbar spine. SUMMARY OF BACKGROUND DATA: The
      Charite Artificial Disc (DePuy Spine, Inc., Raynham, MA) was successful in
      relieving low back pain in the majority of patients, yet there was still a
      significant number of patients who did not obtain pain relief, or their pain even
      worsened. The etiology of their pain is still not known. To our knowledge, no
      study has addressed the effect on the facet joints when the disc height is
      increased. METHODS: CT images passing through the center of the L3-S1 facet
      joints (sagittal plane) were obtained from 15 cadaveric lumbar spine specimens.
      The articulation overlap of facet joints in sagittal plane from the L3 to S1 was
      measured. A 1-mm incremental increase to a total 5 mm in disc space height was
      performed to simulate the changes seen in disc replacement. The change in the
      facet joint articulation overlap in sagittal plane at normal and each
      displacement was then measured. There were 5 lumbar spine specimens dissected to
      validate the technique and standardize the measurements. Mean, percentages, and
      standard deviation values were calculated for all measured dimensions. RESULTS:
      No significant difference was found between the measurements on CT and gross
      specimens (P > 0.05). In 15 specimens, the mean facet joint articulation overlap
      on the sagittal plane was: 16.29 +/- 1.20 mm (left) and 16.22 +/- 1.16 (right) at
      the L3-L4 level; 17.81 +/- 1.18 mm (left) and 17.74 +/- 1.18 mm (right) at the L4
      L5 level; and 18.18 +/- 1.18 mm (left) and 18.23 +/- 1.15 mm (right) at the L5-S1
      level. There is no significant difference between the measured values on left and
      right sides (P > 0.05). Each 1-mm incremental increase in disc space at the L3-L4
      level translated to a decrease in the facet joint articulation overlap in the
      sagittal plane by 6%, and the mean facet joint space increased 0.4 mm. At the L4
      L5 level, the articulation overlap decreased by 6%, and the facet joint space
      increased 0.5 mm. At the L5-S1 level, the articulation overlap decreased by 4%,
      and the facet joint space increased 0.7 mm. CONCLUSIONS: There is a significant
      decrease of the facet joint articulation overlap in sagittal plane and an
      increase in the facet joint space following an increase in the lumbar disc space.
      The inappropriate increase of the height of disc space will result in facet joint
      subluxation.

PMID- 16582841
TI  - Chronic back pain among the elderly: prevalence, associations, and predictors.
AB  - STUDY DESIGN: A longitudinal age homogeneous cohort study. OBJECTIVE: To describe
      the prevalence, nature, and predictors of chronic back pain (CBP) in older
      people. SUMMARY OF BACKGROUND DATA: CBP is a growing source of morbidity among
      the elderly. Few longitudinal studies exist, and its time course and predictors
      are largely undefined. METHODS: The Jerusalem Longitudinal Study assessed 277
      subjects aged 70 years at baseline and 77 years at follow-up. Data collection
      included back pain symptoms, psychosocial, functional, and physical domains.
      RESULTS: The prevalence of CBP increased from 44% to 58% at ages 70 and 77 years,
      respectively, while frequency and severity decreased. CBP was associated with
      female gender, economic difficulties, loneliness, fatigue, poor self-rated
      health, dependence in activities of daily living, joint pain, and obesity.
      Depression was associated at age 70 years, and unemployment, not leaving the
      house for leisure, poor sleep satisfaction, hypertension, and osteoporosis were
      at age 77 years. Predictors of CBP at age 77 years were female gender,
      loneliness, joint pain, hypertension, and preexisting CBP. Unemployment and not
      leaving the house for leisure showed a trend toward significance. CONCLUSION: CBP
      is increasingly common in the elderly. Psychosocial factors, female gender,
      hypertension, and existing joint pain identify individuals most at risk.

PMID- 16582842
TI  - The treatment of acute thoracolumbar burst fractures with transpedicular
      intracorporeal hydroxyapatite grafting following indirect reduction and pedicle
      screw fixation: a prospective study.
AB  - STUDY DESIGN: Prospective consecutive series. OBJECTIVE: To evaluate the outcomes
      of the treatment of acute thoracolumbar burst fractures by transpedicular
      hydroxyapatite grafting following indirect reduction and pedicle screw fixation.
      SUMMARY OF BACKGROUND DATA: In the treatment of thoracolumbar burst fractures,
      the major problem after posterior correction and instrumentation is failure to
      support the anterior spinal column, leading to the loss of correction of kyphosis
      and instrumentation breakage. METHODS: There were 15 consecutive patients who had
      thoracolumbar burst fractures and associated incomplete neurologic deficit. They
      underwent surgery within 4 days of admission, had their implants removed within 1
      year, and were prospectively followed for at least 2 years. Following indirect
      reduction and pedicle screw fixation, transpedicular intracorporeal
      hydroxyapatite grafting to the fractured vertebrae was performed. Median
      operating time was 130 minutes, and median blood loss was 155 g. RESULTS: The
      neurologic function of all 15 patients improved by at least 1 American Spine
      Injury Association grade, with 9 (60%) having complete neurologic recovery.
      Sagittal alignment was improved from a median preoperative kyphosis of 20 degrees
      to -1 degrees (lordosis) by surgery but was found to have slightly deteriorated
      to 1 degrees at final follow-up observation. Computerized tomography showed a
      median spinal canal narrowing of 64%, 22%, and 11%, respectively. There were no
      instances of instrumentation failure. CONCLUSIONS: Posterior indirect reduction,
      transpedicular hydroxyapatite grafting, and pedicle screw fixation could provide
      reliable neurologic improvement in patients with incomplete neurologic deficit,
      and could prevent the development of kyphosis. This technique does not require
      fusion to a segment, thereby preserves thoracolumbar motion.

PMID- 16582844
TI  - Education by general practitioners or education and exercises by physiotherapists
      for patients with whiplash-associated disorders? A randomized clinical trial.
AB  - STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To compare the effectiveness
      of education and advice given by general practitioners (GPs) with education,
      advice, and active exercise therapy given by physiotherapists (PTs) for patients
      with whiplash-associated disorders. SUMMARY OF BACKGROUND DATA: Available
      evidence from systematic reviews has indicated beneficial effects for active
      interventions in patients with whiplash-associated disorders. However, it
      remained unclear which kind of active treatment was most effective. METHODS:
      Whiplash patients with symptoms or disabilities at 2 weeks after accident were
      recruited in primary care. Eligible patients still having symptoms or
      disabilities at 4 weeks were randomly allocated to GP care or physiotherapy. GPs
      and PTs treated patients according to a dynamic multimodal treatment protocol
      primarily aimed to increase activities and influence unfavorable psychosocial
      factors for recovery. We trained all health care providers about the
      characteristics of the whiplash problem, available evidence regarding prognosis
      and treatment, and protocol of the interventions. The content of the information
      provided to patients during treatment depended on the treatment goals set by the
      GPs or PTs. Also, the type of exercises chosen by the PTs depended on the
      treatment goals, and it was not explicitly necessary that exercise therapy was
      provided in all patients. Primary outcome measures included neck pain intensity,
      headache intensity, and work activities. Furthermore, an independent blinded
      assessor measured functional recovery, cervical range of motion, disability,
      housekeeping and social activities, fear of movement, coping, and general health
      status. We assessed outcomes at 8, 12, 26, and 52 weeks after the accident.
      RESULTS: A total of 80 patients were randomized to either GP care (n = 42) or
      physiotherapy (n = 38). At 12 and 52 weeks, no significant differences were found
      concerning the primary outcome measures. At 12 weeks, physiotherapy was
      significantly more effective than GP care for improving 1 of the measures of
      cervical range of motion (adjusted mean difference 12.3 degrees ; 95% confidence
      interval [CI] 2.7-21.9). Long-term differences between the groups favored GP care
      but were statistically significant only for some secondary outcome measures,
      including functional recovery (adjusted relative risk 2.3; 95% CI 1.0-5.0),
      coping (adjusted mean difference 1.7 points; 95% CI 0.2-3.3), and physical
      functioning (adjusted mean difference 8.9 points; 95% CI 0.6-17.2). CONCLUSIONS:
      We found no significant differences for the primary outcome measures. Treatment
      by GPs and PTs were of similar effectiveness. The long-term effects of GP care
      seem to be better compared to physiotherapy for functional recovery, coping, and
      physical functioning. Physiotherapy seems to be more effective than GP care on
      cervical range of motion at short-term follow-up.

PMID- 16582845
TI  - Efficient and stable gene expression in rabbit intervertebral disc cells
      transduced with a recombinant baculovirus vector.
AB  - STUDY DESIGN: A recombinant baculovirus vector expressing GFP (Ac-CMV-GFP) was
      tested in rabbit intervertebral disc cells cultured in monolayer in vitro. Direct
      infection of intervertebral disc cells was then assessed in vivo. OBJECTIVES: To
      test the efficacy of the baculovirus-mediated marked gene transfer to rabbit
      intervertebral disc cells, and the expression of the transgene in vitro and in
      vivo. SUMMARY OF BACKGROUND DATA: The potential application of gene therapy for
      the treatment of degenerative disc disease has been an area of exciting and
      active research. Many efforts have been made toward the construction of delivery
      vectors using mammalian viruses, such as adenovirus, adeno-associated virus,
      retrovirus, and herpesvirus. However, recently, baculovirus-derived vectors have
      emerged as possible tools for gene transfer into mammalian cells in vitro and in
      vivo but, to our knowledge, have never been tested in an intervertebral disc
      cell. METHODS: The intervertebral disc cells cultured in monolayer were treated
      with 6 different doses of baculovirus carrying the green fluorescence protein
      gene (Ac-CMV-GFP). Fluorescence microscopy and flow cytometry were used to
      analyze transgene expression. The Autographa californica nucleopolyhedrovirus/GFP
      virus was then injected directly into the intervertebral discs of 8 rabbits at 7,
      13, 20, and 28 days after injection. The nucleus pulposus tissues of injected
      discs were evaluated immediately by fluorescence microscopy for GFP expression.
      RESULTS: A dose of Ac-CMV-GFP at a multiplicity of infection of 200 achieved the
      highest transduction ratio (approximately 87% of nucleus pulposus cells) and long
      term expression without any toxicity to the cells. In vivo assay showed that Ac
      CMV-GFP could also mediate GFP expression in rabbit intervertebral disc cells
      without inducing any symptoms. The GFP expression level at 7 days after
      transduction was significantly higher than at 21 and 28 days after treatment.
      CONCLUSIONS: Baculovirus can transfer exogenous genes into rabbit nucleus
      pulposus cells at a high efficiency, and safely both in vitro and in vivo. The
      results suggest that baculoviruses might be useful tools as gene therapy vectors
      for intervertebral disc diseases.

PMID- 16582846
TI  - Insulin-like growth factor-1 treatment prevents anti-Fas antibody-induced
      apoptosis in endplate chondrocytes.
AB  - STUDY DESIGN: In vitro investigation of vertebral endplate chondrocyte apoptosis.
      OBJECTIVES: To determine whether Fas antibody caused apoptosis in endplate
      chondrocytes, and whether insulin-like growth factor-1 (IGF-1) inhibited this
      effect. Integrin-alpha1 and focal adhesion kinase (FAK) expression in conjunction
      with apoptosis was also investigated. SUMMARY OF BACKGROUND DATA: Binding of Fas
      antibody to Fas mimics Fas-FasL ligation, which causes apoptosis. IGF-1 has been
      shown to have anti-apoptotic effects. MATERIALS AND METHODS: Rat cervical
      endplate chondrocytes were cultured and treated with Fas antibody, with or
      without IGF-1. Cellular morphology was examined by microscopy. Apoptotic changes
      were evaluated by transmission electron microscopy, TUNEL staining, and
      immunostaining. Apoptosis-induced changes in the expression of integrin-alpha1
      chain and FAK were also investigated. RESULTS: Endplate chondrocytes were able to
      be cultured; a chondrocytic phenotype was maintained. Fas antibody induced
      apoptosis in endplate chondrocytes; this was confirmed by TUNEL staining. Bcl-2
      expression was decreased by Fas antibody, while Bax expression increased.
      Integrin-alpha1 and FAK expression was decreased by Fas antibody. IGF-1 treatment
      inhibited these Fas antibody-induced changes. CONCLUSIONS: Fas antibody induces
      apoptosis and decreases Integrin-alpha1 and FAK expression in cultured endplate
      chondrocytes; IGF-1 is protective against these changes.

PMID- 16582847
TI  - Osteogenic protein-1 injection into a degenerated disc induces the restoration of
      disc height and structural changes in the rabbit anular puncture model.
AB  - STUDY DESIGN: In vivo study of the effect of injection of osteogenic protein-1
      (OP-1) on a rabbit anular needle puncture model of intervertebral disc (IVD)
      degeneration. OBJECTIVE: To study radiographic, magnetic resonance imaging (MRI),
      biochemical, and histologic changes in the rabbit IVD after injection of OP-1
      into the nucleus pulposus in a needle puncture disc degeneration model. SUMMARY
      OF THE BACKGROUND DATA: Growth factors, such as OP-1, have the ability to
      stimulate synthesis of proteoglycans and collagen in vitro. The in vivo injection
      of OP-1 into the normal rabbit IVD has increased disc height and proteoglycan
      content in the anulus fibrosus and nucleus pulposus. However, to our knowledge,
      no attempts have yet been made to determine the effects of these growth factors
      in an in vivo model of disc degeneration. METHODS: New Zealand adolescent white
      rabbits (n = 90, 8 for baseline evaluation, 82 at 8 times) received an anular
      puncture in 2 noncontiguous discs with an 18-gauge needle to induce disc
      degeneration. Four weeks later, either 5% lactose (10 microL) or OP-1 (100 microg
      in 10 microL 5% lactose) was injected into the center of the nucleus pulposus.
      The disc height was followed radiographically for up to 24 weeks after the
      injections. At the 2, 4, 8, 12, and 24-week times after the injection, rabbits
      were euthanized, and MRI of the harvested spinal columns was obtained to grade
      the degeneration. The discs injected with OP-1 or lactose and noninjected discs
      were subjected to biochemical and histologic analysis. The specimens at the 24
      week time were limited to histologic evaluation. RESULTS: The anular puncture
      with a needle induced a consistent disc narrowing within 4 weeks. The injection
      of OP-1 induced a restoration of disc height at 6 weeks, which was sustained for
      the entire experimental period, up to 24 weeks after the injection. The injection
      of lactose alone did not change the course of disc narrowing over the same time.
      MRI grading score showed significant differences between the OP-1 and lactose
      groups at the 8, 12, and 24-week times, suggesting an increase in water content
      in the nucleus pulposus of the OP-1 group. The proteoglycan content of the
      nucleus pulposus and anulus fibrosus was significantly higher in the OP-1 group
      than in the control group. The degeneration grades of the punctured discs in the
      OP-1 group were significantly lower than those in the lactose group. CONCLUSION:
      The results of this study show the feasibility of restoring degenerative rabbit
      discs by a single injection of OP-1 into the nucleus pulposus. Importantly, the
      effects of the OP-1 injection on disc height were sustained for up to 24 weeks.
      The metabolic changes in the cells, following a single injection, might be
      sustained and, thus, induce long-term changes in disc structure. An efficacy
      study in large animals is required to show further that the intradiscal injection
      of OP-1, or bone morphogenetic proteins or growth factors with similar properties
      would be useful for the structural restoration of the IVD in humans.

PMID- 16582848
TI  - Biomechanics of occipitocervical fixation.
AB  - STUDY DESIGN: A human cadaveric biomechanical study comparing occipital fixation
      techniques. OBJECTIVES: To compare ranges of motion between midline and lateral
      occipital fixation and between rigid and nonrigid occipital fixation of an
      unstable craniocervical spine. SUMMARY OF BACKGROUND DATA: New fixation
      techniques using rods and screws increase surgical choice on where fixation is
      placed onto the occiput. Lateral fixation theoretically gives improved resistance
      to deformation because of its increased effective moment arm and bilateral
      purchase. Midline fixation allows significantly longer screw purchase. This study
      compares these two fixation location. METHODS: Cadaveric occipital cervical spine
      specimens were tested biomechanically intact and under six different fixation
      techniques. Range of motion between the skull and C2 at 1.5 N-m and 2 N-m bending
      moments was measured in flexion-extension, lateral bending, and axial rotation.
      Mechanical testing of different rod diameters and a reconstruction plate was
      performed and compared with biomechanical testing. Results were compared between
      the intact condition and all fixations, between the medial and lateral fixations,
      and between the rigid and nonrigid fixations by analysis of variance. RESULTS:
      The range of motion of all constructs was significantly reduced compared with
      intact. Significant differences between groups were only seen in lateral bending
      in fixation placed laterally. Mechanical testing demonstrated that construct
      stiffness was predicted by area moment of inertia of the rod and plate to a
      greater degree than variation in placement of occipital screws or locking of the
      implant. CONCLUSION: The choice of location of occipital fixation should be based
      more on the ease of use and instability pattern. The decreased stiffness of the
      newer small rod systems should be considered.

PMID- 16582849
TI  - Biomechanical assessment of anterior lumbar interbody fusion with an anterior
      lumbosacral fixation screw-plate: comparison to stand-alone anterior lumbar
      interbody fusion and anterior lumbar interbody fusion with pedicle screws in an
      unstable human cadaver model.
AB  - STUDY DESIGN: Human lumbosacral cadaveric specimens were tested in an in vitro
      biomechanical flexibility experiment using physiologic loads in 5 sequential
      conditions. OBJECTIVE: To determine the biomechanical differences between
      anterior lumbar interbody fusion (ALIF) using cylindrical threaded cages alone or
      supplemented with an anterior screw-plate or posterior pedicle screws-rods.
      SUMMARY OF BACKGROUND DATA: Clinically and biomechanically, stand-alone ALIF
      performs modestly in immobilizing the unstable spine. Pedicle screws improve
      fixation stiffness significantly, but supplementary anterior instrumentation has
      not been studied. METHODS: There were 7 specimens tested: (1) intact, (2) after
      discectomy and facetectomy to induce moderate rotational and translational
      hypermobility, (3) with 2 parallel ALIF cages, (4) with cages plus a triangular
      anterior screw-plate, and (5) with cages plus pedicle screws-rods. Pure moments
      without preload induced flexion, extension, lateral bending, and axial rotation;
      linear shear forces induced anteroposterior translation. Angular and linear
      motions were measured stereophotogrammetrically, and range of motion (ROM) and
      stiffness were quantified. RESULTS: Compared to the destabilized spine, interbody
      cages alone reduced ROM by 77% during flexion, 53% during extension, 60% during
      lateral bending, 69% during axial rotation, and 71% during anteroposterior shear
      (P < 0.001, analysis of variance/Fisher least significant difference). Addition
      of an anterior plate or pedicle screws-rods, respectively, further reduced ROM by
      8% or 13% during flexion (P = 0.21), 21% or 28% during extension (P = 0.15), 5%
      or 25% during lateral bending (P = 0.04), 11% or 18% during axial rotation (P =
      0.13), and 18% or 18% during anteroposterior shear (P = 0.17). Compared to stand
      alone ALIF, both the anterior screw-plate and pedicle screw-rod fixation reduced
      vertebral ROM to less than 1.2 degrees of rotation and less than 0.1 mm of
      translation. CONCLUSIONS: The anterior screw-plate and pedicle screws-rods both
      substantially reduced ROM and increased stiffness compared to stand-alone
      interbody cages. There was no significant difference in the amount by which the
      supplementary fixation devices limited flexion, extension, axial rotation, or
      anteroposterior shear; pedicle screws-rods better restricted lateral bending.

PMID- 16582850
TI  - The biomechanics of 1, 2, and 3 levels of vertebral augmentation with
      polymethylmethacrylate in multilevel spinal segments.
AB  - STUDY DESIGN: Experimental biomechanics of multilevel segments with 0, 1, 2, and
      3 vertebral levels of polymethylmethacrylate augmentation. OBJECTIVE: To compare
      multilevel spinal segments with different numbers (0, 1, 2, and 3) of vertebral
      levels augmented with polymethylmethacrylate. SUMMARY OF BACKGROUND DATA: The
      stiffness and strength of single-level polymethylmethacrylate augmentations in
      individual and multilevel vertebrae treated by kyphoplasty and vertebroplasty
      have been studied, but the biomechanics of multilevel segments with more than 1
      vertebral level augmented with polymethylmethacrylate are lacking, yet this is
      clinically relevant in multilevel compression fracture treatment. MATERIALS AND
      METHODS: A total of 48 multilevel segments (T3-T5, T6-T8, T9-T11, T12-L2, and L3
      L5) from 12 spines with known bone mineral density (BMD) were allocated into 6
      groups based on the number of vertebral levels augmented: 0 levels (n = 13),
      control group; 1 level (n = 7), group 2; 2 levels, groups 3, 4, and 5 (n = 7 in
      each); and 3 levels (n = 7), group 6. They were compressed to failure,
      disarticulated into individual vertebrae, and retested. Stiffness and strength
      were statistically analyzed using a univariate analysis of variance comparing the
      main effects, using least significant difference comparisons with 0.05
      probability level. RESULTS: Strength was dependent on BMD (P < 0.001 multilevel
      segments, P < 0.001 individual vertebrae), with no differences among the 6
      different augmentation groups, and no significant differences between augmented
      and nonaugmented individual vertebrae. Stiffness was dependent on BMD (P = 0.009
      multilevel segments, P < 0.004 individual vertebrae), with no significant
      differences among the 6 different augmentation groups, and no significant
      differences between augmented and nonaugmented individual vertebrae. CONCLUSIONS:
      Multilevel segment biomechanics are dependent on BMD and not the pattern of
      augmentation, so the augmentation of fractured vertebrae can be extended to
      adjacent levels at risk for fracture to maintain stiffness and strength, thus
      preventing further fractures.

PMID- 16582852
TI  - Tuberculous spondylitis and pyogenic spondylitis: comparative magnetic resonance
      imaging features.
AB  - STUDY DESIGN: We retrospectively compared magnetic resonance images (MRIs) of
      tuberculous (TB) spondylitis and pyogenic spondylitis. OBJECTIVE: To identify
      differences between the diseases. SUMMARY OF BACKGROUND DATA: Clinical and
      imaging findings of the 2 diseases are hard to distinguish. MRI may show
      important differences and aid in early diagnosis and treatment. METHODS: We
      compared 22 MRI parameters in 33 patients with TB spondylitis (average age, 66
      years) and in 33 patients with pyogenic spondylitis (average age, 65 years).
      RESULTS: Seventeen parameters significantly differed between the groups. The most
      important were local and heterogeneous enhancement of the vertebral body in all
      patients with TB spondylitis, diffuse and homogeneous enhancement of the
      vertebral body in 94% of patients with pyogenic spondylitis, vertebral
      intraosseous abscess with rim enhancement (TB vs. pyogenic, 79% vs. 0%), disc
      abscess with rim enhancement (9% vs. 64%), and well-defined paraspinal abnormal
      signal intensity (82% vs. 18%). CONCLUSIONS: Most parameters occurred in both
      diseases. Distinctive findings were a pattern of bone destruction with relative
      disc preservation and heterogeneous enhancement for TB spondylitis and a diskitis
      pattern (disc destruction) with peridiscal bone destruction and homogeneous
      enhancement for pyogenic spondylitis. These MRI parameters may facilitate the
      differential diagnosis of these diseases.

PMID- 16582851
TI  - Influence of rhBMP-2 on the healing patterns associated with allograft interbody
      constructs in comparison with autograft.
AB  - STUDY DESIGN: A prospective, nonblinded, multicenter study. OBJECTIVE: To
      determine the patterns of allograft incorporation and new bone formation after
      ALIF using stand-alone threaded cortical allograft dowels with either autograft
      or rhBMP-2. SUMMARY OF BACKGROUND DATA: Accelerated healing patterns of allograft
      dowels have been reported in an animal study and a small human study of ALIF with
      rhBMP-2 and bone dowels. METHODS: We enrolled and randomly assigned 131 patients
      with lumbar spondylosis who were undergoing single-level ALIF with allograft
      dowels to either the investigational group who received rhBMP-2 (79 patients) or
      the control group who received autologous bone graft (52 patients). Independent
      radiologists used plain radiographs and computed tomography scans to evaluate
      fusion. Allograft incorporation was assessed using a modified Bridwell-Lenke
      scale, and changes in bone density within the adjacent vertebral bodies were
      monitored. RESULTS: At 12 months, all investigational patients had radiographic
      evidence of new bone formation and incorporation of the allografts into the
      adjacent vertebral endplates; there were no changes in fusion status at 24
      months. Fusions were documented in 89% of patients in the control group at 12
      months. The percentage declined to 81.5% at 24 months with 10% of the patients in
      the autograft group showing incomplete healing and 11% having no healing of the
      allograft dowels. On CT scans, 14 of the investigational patients (14 of 79; 18%)
      developed a transient, localized area of bone remodeling within the vertebral
      body adjacent to the allograft dowel. All were healed by 24 months. The transient
      appearance of these zones had no effect on clinical outcomes. No patient in the
      control group developed bone remodeling zones. CONCLUSION: We think that the use
      of rhBMP-2 is a promising method of facilitating allograft dowel incorporation
      and new bone formation in patients undergoing ALIF with allograft dowels.

PMID- 16582853
TI  - Risk factors for recurrent episodes of work-related low back disorders in an
      industrial population.
AB  - STUDY DESIGN: An observational longitudinal design. OBJECTIVES: To characterize
      the rate of and risk factors for recurrent episodes of work-related low back
      disorder in industrial workers. SUMMARY OF BACKGROUND DATA: Little data exist on
      risk factors for recurrent episodes of work-related low back disorders in
      employed persons. METHODS: A total of 352 active hourly union employees who were
      diagnosed with a recent work-related low back disorder and who had at least one
      follow-up visit within 12 months enrolled for participation in a rehabilitation
      intervention study at the workplace. Information on clinical and job factors was
      obtained at each study visit. Job risk for low back disorder was quantified using
      the Lumbar Motion Monitor. The main outcome measure, recurrence of work-related
      low back pain, was derived from a computerized file of administrative records of
      visits to the plant's medical department. RESULTS: The rate of repeated episodes
      was 24.4%; an additional episode occurred in 2.3%. Adjusting for age, gender,
      health status and job exposures, lower levels of physical health, increasing back
      pain disability, spinal deformity, high stress, and increasing number of
      different jobs worked at the same plant were risk factors for a recurrent
      episodes of low back pain. CONCLUSIONS: Early identification of risk factors for
      a work-related low back disorder may signal the need for early and intense
      rehabilitation to prevent recurrent episodes. Because these findings were based
      on jobs with medium risk of low back disorders, other factors may be significant
      in higher risk jobs.

PMID- 16582854
TI  - Epidemiology of traumatic spinal cord injury in Canada.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To describe the incidence,
      clinical features, and treatment of traumatic spinal cord injury (SCI) treated at
      a Canadian tertiary care center. SUMMARY OF BACKGROUND DATA: Understanding the
      current epidemiology of acute traumatic SCI is essential for public resource
      allocation and primary prevention. Recent reports suggest that the mean age of
      patients with SCI may be increasing. METHODS: We retrospectively reviewed
      hospital records on all patients with traumatic SCI between January 1997 and June
      2001 (n = 151). Variables assessed included age, gender, length of
      hospitalization, type and mechanism of injury, associated spinal fractures,
      neurologic deficit, and treatment. RESULTS: Annual age-adjusted incidence rates
      were 42.4 per million for adults aged 15-64 years, and 51.4 per million for those
      65 years and older. Motor vehicle accidents accounted for 35% of SCI. Falls were
      responsible for 63% of SCI among patients older than 65 years and for 31% of
      injuries overall. Cervical SCI was most common, particularly in the elderly, and
      was associated with fracture in only 56% of cases. Thoracic and lumbar SCI were
      associated with spinal fractures in 100% and 85% of cases, respectively. In
      hospital mortality was 8%. Mortality was significantly higher among the elderly.
      Treatment of thoracic and lumbar fractures associated with SCI was predominantly
      surgical, whereas cervical fractures were equally likely to be treated with
      external immobilization alone or with surgery. CONCLUSION: A large proportion of
      injuries was seen among older adults, predominantly as a result of falls.
      Prevention programs should expand their focus to include home safety and
      avoidance of falls in the elderly.

PMID- 16582856
TI  - Responsiveness of objective, disease-specific, and generic outcome measures in
      patients with chronic low back pain: an assessment for improving, stable, and
      deteriorating patients.
AB  - STUDY DESIGN: Analysis of outcome data collected prospectively from 250 patients
      recruited to the UK Spine Stabilization Trial. OBJECTIVES: To compare the
      responsiveness of the Shuttle Walking Test (SWT), which is an objective outcome
      measure, with that of a disease-specific (the Oswestry Disability Index) and 2
      generic (the EQ-5D and SF-36) instruments in patients with chronic low back pain
      (LBP). SUMMARY OF BACKGROUND DATA: Studies assessing the performance of
      subjective disease-specific and generic measures have increased in recent years,
      although there is a paucity of research reporting the responsiveness of objective
      measures in patients with LBP. The focus of investigation has been on
      responsiveness to improvements in LBP symptoms. For patients with deteriorating
      health, it remains largely unclear how outcome instruments perform. METHODS:
      Baseline and 12-month outcome data collected on 250 patients with chronic LBP
      recruited to the Spine Stabilization Trial were analyzed using traditional
      measures of responsiveness. Analyses were performed for 3 groups of patients:
      those who rated their health status as improved, deteriorated, and stable at 12
      months. RESULTS: The SWT was shown by all measures to be responsive to health
      improvement, although less so than other instruments. All instruments were able
      to detect small-to-moderate reductions in health. Instrument floor effects may be
      responsible for small SF-36 change scores recorded for deteriorating patients.
      CONCLUSIONS: Although shown to be responsive, including the SWT alongside disease
      specific and generic instruments is unlikely to add additional information. All
      instruments appear responsive to patient deterioration, however, further research
      for the SF-36 is required.

PMID- 16582857
TI  - Emotional health predicts pain and function after fusion: a prospective
      multicenter study.
AB  - STUDY DESIGN: Prospective. OBJECTIVES: To assess whether patients with poorer
      emotional health before fusion surgery will have worse pain and function after
      surgery, and to identify patient variables that predict fusion outcomes. SUMMARY
      OF BACKGROUND DATA: A systematic review of fusion outcomes studies reported an
      average of 68% "satisfactory" outcomes. The persistence of pain and functional
      limitations leads to emotional and financial costs. Therefore, it is important to
      identify the factors that affect fusion outcome. Research has explored
      psychosocial factors (e.g., depression, anxiety) as being important outcome
      predictors. METHODS: Data from subjects enrolled in a multisite trial of 2 fusion
      systems were analyzed. Subjects completed measures of health-related quality of
      life (SF-36), pain (visual analog scale), and function (Oswestry Disability
      Index). A total of 160 subjects completed measures before fusion, 155 completed
      measures 12 months after fusion, and 115 completed measures 24 months after
      fusion. Subject variables (i.e., age, gender, smoking, workers' compensation, and
      second surgery status) and presurgical pain/function were regressed on
      pain/function outcomes after surgery. This model was compared to one that
      included presurgical Mental Component Scores (MCSs), which is a SF-36 derived
      measure of emotional health, to determine whether MCS data significantly improved
      the prediction of pain/function. RESULTS: Higher presurgical MCS (i.e., better
      emotional health) predicted less back and leg pain after surgery. Similarly,
      higher presurgical MCS predicted better physical function after surgery. Other
      important predictors of pain and function were presurgical pain and function,
      workers' compensation, and smoking status. The associations were modest (2% to 9%
      of independent variance accounted for), but significant. CONCLUSIONS: Presurgical
      emotional status is one significant predictor of pain and function outcomes up to
      2 years after fusion. Other significant predictors included workers' compensation
      status, smoking status, and presurgical pain/function. Studies to identify and
      intervenewith patients with poorer emotional status will clarify whether
      presurgical mental health intervention can improve pain and function outcomes
      after surgery or whether these patients are not candidates for surgery.

PMID- 16582855
TI  - Descriptive epidemiology and prior healthcare utilization of patients in the
      Spine Patient Outcomes Research Trial's (SPORT) three observational cohorts: disc
      herniation, spinal stenosis, and degenerative spondylolisthesis.
AB  - STUDY DESIGN: Prospective observational cohorts. OBJECTIVE: To describe
      sociodemographic and clinical features, and nonoperative (medical) resource
      utilization before enrollment, in patients who are candidates for surgical
      intervention for intervertebral disc herniation (IDH), spinal stenosis (SpS), and
      degenerative spondylolisthesis (DS) according to SPORT criteria. SUMMARY OF
      BACKGROUND DATA: Intervertebral disc herniation, spinal stenosis, and
      degenerative spondylolisthesis with stenosis are the three most common diagnoses
      of low back and leg symptoms for which surgery is performed. There is a paucity
      of descriptive literature examining large patient cohorts for the relationships
      among baseline characteristics and medical resource utilization with these three
      diagnoses. METHODS: The Spine Patient Outcomes Research Trial (SPORT) conducts
      three randomized and three observational cohort studies of surgical and
      nonsurgical treatments for patients with IDH, SpS, and DS. Baseline data include
      demographic information, prior treatments received, and functional status
      measured by SF-36 and the Oswestry Disability Index (ODI-AAOS/Modems version).
      The data presented represent all 1,411 patients (743 IDH, 365 SpS, 303 DS)
      enrolled in the SPORT observational cohorts. Multiple logistic regression was
      used to generate independent predictors of utilization adjusted for
      sociodemographic variables, diagnosis, and duration of symptoms. RESULTS: The
      average age was 41 years for the IDH group, 64 years for the SpS group, and 66
      years for the DS group. At enrollment, IDH patients presented with the most pain
      as reported on the SF-36 (BP 26.3 vs. 33.2 SpS and 33.8 DS) and were the most
      impaired (ODI 51 vs. 42.3 SpS and 41.5 DS). IDH patients used more chiropractic
      treatment (42% vs. 33% SpS and 26% DS), had more Emergency Department (ED) visits
      (21% vs. 7% SpS and 4% DS), and used more opiate analgesics (49% vs. 29% SpS and
      27% DS). After adjusting for age, gender, diagnosis, education, race, duration of
      symptoms, and compensation, Medicaid patients used significantly more opiate
      analgesics (58% Medicaid vs. 41% no insurance, 42% employer, 33% Medicare, and
      32% private) and had more ED visits compared with other insurance types (31%
      Medicaid vs. 22% no insurance, 16% employer, 3% Medicare, and 11% private).
      CONCLUSION: IDH patients appear to have differences in sociodemographics,
      resource utilization, and functional impairment when compared with the SpS/DS
      patients. In addition, the differences in resource utilization for Medicaid
      patients may reflect differences in access to care. The data provided from these
      observational cohorts will serve as an important comparison to the SPORT
      randomized cohorts in the future.

PMID- 16582858
TI  - Confidence in spine training among senior neurosurgical and orthopedic residents.
AB  - STUDY DESIGN: A cross-sectional survey of senior neurosurgical and orthopedic
      residents. OBJECTIVE: To evaluate the confidence of senior orthopedic and
      neurosurgery residents in performing spinal surgical procedures and their need
      for further training. The content and exposure to spine training as well as
      anticipated practice profile were characterized. SUMMARY OF BACKGROUND DATA:
      Spinal surgery is performed by specialists with backgrounds in orthopedic surgery
      and neurosurgery. As this subspecialty evolves, the need to modify training
      programs to keep up with technological and medical advances becomes increasingly
      clear. The primary objective of this study was to evaluate the self-assessed
      confidence and perceived need for further training of senior orthopedic and
      neurosurgical residents in performing a number of spinal surgical procedures.
      METHODS: An evaluation of self-assessed surgical competence of senior orthopedic
      and neurosurgery residents in Canada was undertaken by mail-out questionnaire. A
      follow-up questionnaire was mailed to nonresponders 3 months later. Survey
      results were summarized using SPSS statistical software, and descriptive and
      comparative analyses were performed. RESULTS: Significant differences in time and
      exposure to spine training differentiated the neurosurgical and orthopedic
      residencies (37% and 16% of total residency time devoted to spine, respectively).
      Neurosurgical residents reported significantly higher levels of confidence for
      all 25 surgical procedures. Of those residents anticipating incorporating spine
      into their practice, 29% of neurosurgery residents planned on entering a spine
      fellowship compared with 17% of their orthopedic colleagues. CONCLUSIONS:
      Training in spine surgery constitutes a considerably larger proportion of
      neurosurgery residency than orthopedic residency. Neurosurgery residents graduate
      with significantly higher levels of confidence to perform spine surgery, while
      orthopedic residents report significantly higher need for additional training in
      spine surgery. The majority of neurosurgery graduates report that they will
      include spine in their clinical practice, while most orthopedic graduates will
      exclude it.

PMID- 16582859
TI  - Point of view: confidence in spine training among senior neurosurgical and
      orthopedic residents.

PMID- 16582860
TI  - Disturbed paraspinal reflex following prolonged flexion-relaxation and recovery.
AB  - STUDY DESIGN: Repeated measures experimental study of the effect of flexion
      relaxation, recovery, and gender on paraspinal reflex dynamics. OBJECTIVE: To
      determine the effect of prolonged flexion-relaxation and recovery time on reflex
      behavior in human subjects. SUMMARY OF BACKGROUND DATA: Prolonged spinal flexion
      has been shown to disturb the paraspinal reflex activity in both animals and
      human beings. Laxity in passive tissues of the spine from flexion strain may
      contribute to desensitization of mechanoreceptors. Animal studies indicate that
      recovery of reflexes may take up to several hours. Little is known about human
      paraspinal reflex behavior following flexion tasks or the recovery of reflex
      behavior following the flexion tasks. METHODS: A total of 25 subjects performed
      static flexion-relaxation tasks. Paraspinal muscle reflexes were recorded before
      and immediately after flexion-relaxation and after a recovery period. Reflexes
      were quantified from systems identification analyses of electromyographic
      response in relation to pseudorandom force disturbances applied to the trunk.
      RESULTS: Trunk angle measured during flexion-relaxation postures was
      significantly higher following static flexion-relaxation tasks (P < 0.001),
      indicating creep deformation of passive supporting structures in the trunk.
      Reflex response was diminished following flexion-relaxation (P < 0.029) and
      failed to recover to baseline levels during 16 minutes of recovery. CONCLUSION:
      Reduced reflex may indicate that the spine is less stable following prolonged
      flexion-relaxation and, therefore, susceptible to injury. The absence of recovery
      in reflex after a substantial time indicates that increased low back pain risk
      from flexion-relaxation may persist after the end of the flexion task.

PMID- 16582862
TI  - Re: Vaccaro AR, Patel T, Fischgrund J, et al. A pilot study evaluating safety and
      efficacy of OP-1 putty (rhBMP-7) as a replacement for iliac crest autograft in
      posterolateral lumbar arthrodesis for degenerative spondylolisthesis. Spine
      2004;29:1885-92.

PMID- 16582861
TI  - Have cranio-vertebral junction anomalies been overlooked as a cause of vertebro
      basilar insufficiency?
AB  - STUDY DESIGN: A prospective controlled study using single photon emission
      computed tomography (SPECT) to assess cerebellar perfusion in a cohort of 19
      patients with congenital cranio-vertebral junction (CVJ) anomalies, with or
      without vertebro-basilar insufficiency (VBI). OBJECTIVE: To correlate symptoms of
      VBI with the presence of posterior circulation ischemia in patients with
      congenital CVJ anomalies, using technetium 99m ethylene cystine dimer SPECT.
      SUMMARY OF BACKGROUND DATA: Patients with VBI are rarely investigated for CVJ
      anomalies, despite the fact that a significant number of patients with congenital
      CVJ anomalies has VBI. There are also no studies quantifying outcome of surgical
      interventions, such as like occipito-cervical fusion, in patients with VBI and
      CVJ anomalies. METHODS: There were 19 consecutive patients with congenital CVJ
      anomalies who were scheduled for combined transoral odontoidectomy and occipito
      cervical fusion were included in the study. Technetium 99m ethylene cystine dimer
      brain SPECT and clinical assessment of all patients was performed in the
      preoperative period and at 4 weeks after surgery. Before surgery, patients were
      divided into 2 groups depending on the clinical findings: (1) symptomatic group,
      consisting of 12 patients having features suggestive of VBI (drop attacks,
      episodic vertigo, visual disturbances and dysarthria); and (2) control group,
      consisting of 7 patients without symptoms of VBI. RESULTS: SPECT showed decreased
      cerebellar perfusion in 75% (n = 9) of patients in the symptomatic group compared
      to 14% (n = 1) in the control group before surgery (Fisher exact 2-tailed test, P
      = 0.019). Following surgery, 8 patients (88.9%) in the symptomatic group and none
      in the control group had improvement in cerebellar perfusion. Two patients in the
      symptomatic group who had meningitis develop during the postoperative period had
      a decrease in cerebellar perfusion on follow-up SPECT. Clinically, all patients
      with improvement in cerebellar perfusion had improvement in the symptoms of VBI
      at 1 month of follow-up. CONCLUSIONS: A significant number of patients with
      congenital CVJ anomalies who have symptoms of VBI develop have decreased
      cerebellar perfusion shown by SPECT. Rigid internal fixation of the CVJ may
      alleviate symptoms and improve posterior circulation in some of these patients.

PMID- 16582864
TI  - [A randomized study comparing amoxicillin-clavulanic acid with cefazolin as
      antimicrobial prophylaxis in laparotomic gynecologic surgery].
AB  - AIM: The aim of this paper was to compare amoxicillin-clavulanic acid with
      cefazolin as ultra-short term prophylaxis in laparotomic gynecologic surgery.
      METHODS: A prospective randomized study was conducted to compare 2 antimicrobial
      regimens in the surgical prophylaxis of laparotomic surgery. Patients were
      randomly allocated to receive amoxicillin-clavulanic acid (2.2 g, group A) or
      cefazolin (2 g, group B) as a single dose 30 min before surgery. Each patient was
      assessed daily until discharge to evidence febrile status and the presence of
      infections at the operative site, urinary tract and respiratory tract. RESULTS:
      In the amoxicillin-clavulanic acid (group A) and cefazolin (group B) groups,
      overall 346 and 352 patients, respectively, were evaluable for prophylactic
      efficacy at hospital discharge. Infectious complications were infrequent in both
      arms. Febrile morbidity occurred in 21 (6.1%) and 26 (7.4%) patients respectively
      in the amoxicillin-clavulanic acid and cefazolin groups. Wound infection and
      urinary tract infection were also higher, but not significantly in the cefazolin
      group (1.1% versus 0.5% and 2.5% versus 2%, respectively). There was one
      respiratory tract infection (0.2%) in group B and no septic death in either
      groups. CONCLUSIONS: Ultra-short term prophylaxis with both amoxicillin
      clavulanic acid and cefazolin is safe in elective laparotomic gynecologic
      surgery.

PMID- 16582865
TI  - Teratological risk evaluation and prevention of voluntary abortion.
AB  - AIM: Many women exposed to completely innocuous agents during pregnancy have a
      high perception of adverse effects to such an extent that they may interrupt
      their pregnancy. The objective of our study is to evaluate the importance of the
      perception of the risk level in making the decision to end the pregnancy and the
      relevance that a teratology consultation can have in preventing unmotivated
      terminations of pregnancy METHODS: We carried out a survey on 350 women in Rome
      who voluntarily interrupted their pregnancy to evaluate the prevalence due to
      presumed teratogen. Contemporarily we studied the pregnancy outcomes, the
      clinical, the psychological and the socio-economic factors of 142 women who
      contacted our Teratology Information Service (TIS) in the 1(st)trimester of
      pregnancy because suspected of teratogen exposure: 72 decided to terminate their
      pregnancy, whereas 70 were used as a control group. RESULTS: On 350 women who
      voluntarily interrupted their pregnancy, 4 cases (1.4%) reported exposure to a
      suspected teratogen, but our evaluation determined only 1 case. On 72 women
      decided to terminate their pregnancy and who contacted our TIS, after counselling
      73% continued their pregnancy with respect to 97% of the control group. Those
      women who interrupted their pregnancy did so because of personal reasons
      independently to or the type of exposure or the risk attributed by us.
      CONCLUSIONS: From our data it appears that a percentage of voluntary abortions is
      related to suspected teratogen exposure and that TIS are effective in the
      prevention of this kind of voluntary abortions caused by groundless fears.

PMID- 16582866
TI  - [Vaginal intraepithelial neoplasia and human papillomavirus infection: a report
      of 75 cases].
AB  - AIM: Vaginal intraepithelial neoplasia (VaIN) is an uncommon and poorly
      understood disease. Risk factors other than human papillomavirus (HPV) infection
      could be linked to the onset and evolution of some VaIN. METHODS: In this paper,
      the results achieved from the analysis of 75 patients with VaIN are reported.
      From these cases, women with HIV, previous hysterectomy, autoimmune diseases and
      radio- and chemotherapy have been excluded. Thus, most of these selected cases
      should be linked to the HPV infection. They have been examined after a
      distinction between grade and association with coilocytosis. VaIN preferential
      localization, mean age of patients and manifestation pattern after vaginal
      colposcopy have then been examined. RESULTS: Although the population size cannot
      allow evidences, it seems that VaIN with coilocytosis and VaIN I without
      coilocytosis have preferential localization in the upper third of the vagina. It
      does not appear that mean age of patients for each grade of VaIN differs
      significativly, both associated and not associated with coilocytosis. Finally,
      after vaginal colposcopy, the pattern of VaIN for each grade is absolutely not
      typical, and it seems that white thin epithelium or negative Lugol area are
      usually the manifestation of high grades of VaIN too. CONCLUSIONS: These results,
      if confirmed, could mean that VaIN due to HPV may have a different natural
      history relating to the site of localization in the vagina and, moreover, that
      also VaIN of high grade could appear with an innocent vaginal pattern.

PMID- 16582867
TI  - Metabolic syndrome in polycystic ovary syndrome.
AB  - Because insulin resistance and visceral obesity are important features of
      polycystic ovary syndrome (PCOS), metabolic syndrome is much more common in women
      with PCOS than in the general female population of similar age. It has been
      reported that in the USA almost 50% of women with PCOS present the metabolic
      syndrome. In Italy, where women with PCOS have a lower mean body weight and less
      frequently increased serum triglycerides than US PCOS, metabolic syndrome is less
      common but still 4 times more frequent in PCOS patients than in the general
      female population of similar age. Patients with mild PCOS phenotype (ovulatory
      PCOS) have a lower prevalence of metabolic syndrome but, in these patients too,
      metabolic syndrome is 2 times more frequent than in the normal population. These
      data suggest that PCOS is the most common cause of increased cardiovascular risk
      in young adult women. All obese and overweight women with PCOS should be screened
      for metabolic syndrome and, when the syndrome is not found, the screening should
      be repeated every 2 or 3 years. Treatment consists in lifestyle intervention.
      Pharmacological therapies should be used only when lifestyle fails to normalize
      cardiovascular risk factors.

PMID- 16582868
TI  - Ovulation induction in infertile patients with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is the major cause of anovulatory infertility.
      Throughout the years, several and effective medical and surgical therapies have
      been proposed to treat the ovarian dysfunction. To date, new effective and cheap
      drugs, such as metformin and aromatase inhibitors, are available. The aim of the
      present descriptive review is to describe the main therapeutic approaches for
      treating infertile patients with PCOS.

PMID- 16582869
TI  - Management of menopause.
AB  - Menopause signifies the permanent cessation of ovarian function and the end of a
      woman's reproductive potential. A universal experience in women's aging, it is
      the culmination of many years of reproductive aging; a process that unfolds as a
      continuum from birth through ovarian senescence to the menopausal transition and
      the postmenopause. The menopausal transition is known to play a major role in the
      etiology of many symptoms common in middle age and may contribute to chronic
      conditions and disorders of aging such as osteoporosis, cardiovascular diseases
      and cancer. Recent data suggest an unacceptable increase in morbidity in a number
      of women using hormone therapy (HT). Thus, during the past few years, many women
      and doctors have revised their opinions on HT for menopause-related symptoms, and
      a substantial number of individuals have discontinued its use because of concerns
      about side-effects, owing to this, numerous alternatives to HT are promoted, and
      researches have pointed out the interest in a group of molecules such as
      selective estrogen receptor modulators (SERMs) (i.e. raloxifene) and
      phytoestrogens. Further studies may open a new panorama in patient-specific
      management of postmenopausal health. Careful assessment of the midlife woman
      allows for individualized risk-benefit analysis with the formulation of a
      specific health management plan.

PMID- 16582870
TI  - Endocrinology of the aging male.
AB  - Despite enormous medical progress during the past few decades, the last years of
      life are still accompanied by increasing ill health and disability. The ability
      to maintain active and independent living for as long as possible is a crucial
      factor for ageing healthily and with dignity. The most important and drastic
      gender differences in aging are related to the reproductive organs. In
      distinction to the course of reproductive ageing in women, with the rapid decline
      in sex hormones expressed by the cessation of menses, men experience a slow and
      continuous decline. This decline in endocrine function involves: a decrease of
      testosterone, dehydro epiandrosterone (DHEA), oestrogens, thyroid stimulating
      hormone (TSH), growth hormone (GH), IGF1, and melatonin. The decrease of sex
      hormones is concomitant with a temporary increase of luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH). In addition sex hormone binding globulins
      (SHBG) increase with age resulting in further lowering the concentrations of free
      biologically active androgens. These hormonal changes are directly or indirectly
      associated with changes in body constitution, fat distribution (visceral
      obesity), muscle weakness, osteopenia, osteoporosis, urinary incontinence, loss
      of cognitive functioning, reduction in well being, depression, as well as sexual
      dysfunction. The laboratory and clinical findings of partial endocrine
      deficiencies in the aging male will be described and discussed in detail. With
      the prolongation of life expectancy both women and men today live 1/3 of their
      life with endocrine deficiencies. Interventions such as hormone replacement
      therapy may alleviate the debilitating conditions of secondary partial endocrine
      deficiencies by preventing the preventable and delaying the inevitable.

PMID- 16582871
TI  - [Management of gynecological tumors associated with BRCA1 and BRCA2 germline
      mutations. Case report and literature review].
AB  - Genetic investigation of BRCA1 and BRCA2 germline mutations is, nowadays, a
      diagnostic procedure with practical clinical applications. The role of this genes
      in DNA repair and stability and in cancer development is now well recognised.
      Most involved are breast and ovarian cancers, but, less frequently, other
      gynecological cancers like cervical, corpus uteri and Fallopian tubes cancers and
      also other non gynecological malignancies. We report the case of a 67-year-old
      patient with strong familiarity for breast cancer, with a BRCA2 germline
      mutation, who developed in 30 months 4 primary malignancies: in chronological
      order, breast cancer, chronic lymphatic leukemia, and synchronous ovarian and
      endocervical adenocarcinoma. A better knowledge of the biological and clinical
      behaviour of BRCA related cancers is of strategical importance in the management
      of patients with strong familiar neoplastic history or with genetic test
      positivity. An adequate counselling can help in the management of these cancers
      in the prevention and early diagnosis taking also into consideration the
      possibility of a prophylactic surgery.

PMID- 16582872
TI  - [Primary genital herpes infection in pregnancy].
AB  - A case report of primary genital herpes infection in a 36-years old pregnant
      woman during her second pregnancy is presented; the patient was treated according
      to American College of Obstetricians and Gynecologists guidelines. Maternal
      primary herpes simplex virus (HSV) genital infection arose at the 16th week of
      gestation and treated orally with acyclovir 400 mg 3 times a day for a period of
      10 days. Nested polymerase chain reaction (PCR), positive on vaginal swab,
      resulted negative on the maternal serum and on the amniotic fluid (at the 21st
      week). The patient was monitored for the rest of her pregnancy and she received a
      suppressive oral acyclovir therapy (400 mg 3 times daily) from the 36th week of
      gestation until the vaginal delivery, occurred spontaneously at the 38th week
      with an HSV negative vaginal swab. The live male infant, weighing 3,050 g and
      with Apgar scores of 7-9 at 1 and 5 min, was delivered and in repeated clinical
      examinations resulted negative to HSV laboratory investigations with no evidence
      of herpes infection or adverse effects due to acyclovir therapy.

PMID- 16582873
TI  - A false visualization of ureteral jet with Doppler sonography during transvaginal
      evaluation of ureterocele.
AB  - A case of ureterocele diagnosed by an experimental trial using transvaginal
      ultrasound is reported. Color Doppler sonography revealed a jet flowing from the
      ureterocele into bladder. The radionuclide renal scan revealed a right duplex
      system, a ureterocele of the upper moiety and its functional obstruction. If the
      upper moiety was obstructed, where was the ureteral jet from? We can suppose that
      the jet visualized was flowing from the ureteral meatus of the lower moiety,
      positioned behind the ureterocele, and not from the ureterocele itself. In the
      light of this case, a urinary obstruction could not be excluded only on the basis
      of Doppler sonographic findings. In conclusion, a diagnostic work-up using only
      transvaginal ultrasound is insufficient to adeguately analyse the anatomy and
      function of the urinary system, especially when there are anatomy malformations.

PMID- 16582874
TI  - Pure lipoma of the uterus.

PMID- 16582875
TI  - Drug therapy of the metabolic syndrome: minimizing the emerging crisis in
      polypharmacy.
AB  - The metabolic syndrome--a collection of factors associated with increased risk
      for cardiovascular disease and diabetes--is becoming increasingly common, largely
      as a result of the increase in the prevalence of obesity. Although it is
      generally agreed that first-line clinical intervention for the metabolic syndrome
      is lifestyle change, this is insufficient to normalize the risk factors in many
      patients, and so residual risk could be high enough to justify drug therapy.
      However, at present there are no approved drugs that can reliably reduce all of
      the metabolic risk factors over the long term, and so there is growing interest
      in therapeutic strategies that might target multiple risk factors more
      effectively, thereby minimizing problems with polypharmacy. This review
      summarizes current understanding of the nature of the metabolic syndrome, and
      discusses each of the risk factors of the metabolic syndrome as possible primary
      drug targets; potential secondary or tertiary targets are also considered.

PMID- 16582877
TI  - Lipid phosphatases as drug discovery targets for type 2 diabetes.
AB  - The soaring incidence of type 2 diabetes has created pressure for new
      pharmaceutical strategies to treat this devastating disease. With much of the
      focus on overcoming insulin resistance, investigation has focused on finding ways
      to restore activation of the phosphatidylinositol 3'-kinase pathway, which is
      diminished in many patients with type 2 diabetes. Here we review the evidence
      that lipid phosphatases, specifically PTEN and SHIP2, attenuate this important
      insulin signalling pathway. Both in vivo and in vitro studies indicate their role
      in regulating whole-body energy metabolism, and possibly weight gain as well. The
      promise and challenges presented by this new class of drug discovery targets will
      also be discussed.

PMID- 16582878
TI  - Cellular imaging in drug discovery.
AB  - Traditional screening paradigms often focus on single targets. To facilitate drug
      discovery in the more complex physiological environment of a cell or organism,
      powerful cellular imaging systems have been developed. The emergence of these
      detection technologies allows the quantitative analysis of cellular events and
      visualization of relevant cellular phenotypes. Cellular imaging facilitates the
      integration of complex biology into the screening process, and addresses both
      high-content and high-throughput needs. This review describes how cellular
      imaging technologies contribute to the drug discovery process.

PMID- 16582876
TI  - Multiplexed protein measurement: technologies and applications of protein and
      antibody arrays.
AB  - The ability to measure the abundance of many proteins precisely and
      simultaneously in experimental samples is an important, recent advance for static
      and dynamic, as well as descriptive and predictive, biological research. The
      value of multiplexed protein measurement is being established in applications
      such as comprehensive proteomic surveys, studies of protein networks and
      pathways, validation of genomic discoveries and clinical biomarker development.
      As standards do not yet exist that bridge all of these applications, the current
      recommended best practice for validation of results is to approach study design
      in an iterative process and to integrate data from several measurement
      technologies. This review describes current and emerging multiplexed protein
      measurement technologies and their applications, and discusses the remaining
      challenges in this field.

PMID- 16582879
TI  - Interaction with Grb14 results in site-specific regulation of tyrosine
      phosphorylation of the insulin receptor.
AB  - The dynamics of interaction of the insulin receptor (IR) with Grb14 was
      monitored, in real time, in living human embryonic kidney cells, using
      bioluminescence resonance energy transfer (BRET). We observed that insulin
      rapidly and dose-dependently stimulated this interaction. We also observed that
      insulin-induced BRET between the IR and protein tyrosine phosphatase 1B (PTP1B)
      was markedly reduced by Grb14, suggesting that Grb14 regulated this interaction
      in living cells. Using site-specific antibodies against phosphorylated tyrosines
      of the IR, we showed that Grb14 protected the three tyrosines of the kinase loop
      from dephosphorylation by PTP1B, while favouring dephosphorylation of tyrosine
      972. This resulted in decreased IRS-1 binding to the IR and decreased activation
      of the extracellular signal-regulated kinase pathway. Increased Grb14 expression
      in human liver-derived HuH7 cells also seemed to specifically decrease the
      phosphorylation of Y972. Our work therefore suggests that Grb14 may regulate
      signalling through the IR by controlling its tyrosine dephosphorylation in a site
      specific manner.

PMID- 16582880
TI  - Increased p53 activity does not accelerate telomere-driven ageing.
AB  - There is a great interest in determining the impact of p53 on ageing and, for
      this, it is important to discriminate among the known causes of ageing. Telomere
      loss is a well-established source of age-associated damage, which by itself can
      recapitulate ageing in mouse models. Here, we have used a genetic approach to
      interrogate whether p53 contributes to the elimination of telomere-damaged cells
      and its impact on telomere-driven ageing. We have generated compound mice
      carrying three functional copies of the p53 gene (super-p53) in a telomerase
      deficient background and we have measured the presence of chromosomal
      abnormalities and DNA damage in several tissues. We have found that the in vivo
      load of telomere-derived chromosomal damage is significantly decreased in super
      p53/telomerase-null mice compared with normal-p53/telomerase-null mice.
      Interestingly, the presence of extra p53 activity neither accelerates nor delays
      telomere-driven ageing. From these observations, we conclude that p53 has an
      active role in eliminating telomere-damaged cells, and we exclude the possibility
      of an age-promoting effect of p53 on telomere-driven ageing.

PMID- 16582881
TI  - Wiskott-Aldrich syndrome protein is involved in alphaIIb beta3-mediated cell
      adhesion.
AB  - The Wiskott-Aldrich syndrome (WAS) is an X-chromosome-linked immunodeficiency
      disorder. The most common symptom seen in WAS patients is bleeding. One of the
      main causes of bleeding is defective platelet aggregation. The causative gene of
      WAS encodes WAS protein (WASP). Here, we show that WASP binds to the calcium- and
      integrin-binding protein (CIB) in platelets. CIB was originally identified as a
      protein binding to the alphaIIb cytoplasmic tail of platelet integrin alphaIIb
      beta3, which has a primary role in platelet aggregation. We also show that the
      WASP-CIB complex is important in alphaIIb beta3-mediated cell adhesion, and that
      in patients mutant forms of WASP are expressed at reduced levels or show lower
      affinities for CIB than wild-type WASP. Our results indicate that impaired
      complex formation between mutant WASPs and CIB reduces alphaIIb beta3-mediated
      cell adhesion and causes defective platelet aggregation, resulting in bleeding.

PMID- 16582882
TI  - Warming up at the poles.

PMID- 16582888
TI  - APHIS, FDA, and NIH issue memorandum of understanding on laboratory animal
      welfare.

PMID- 16582889
TI  - Conference wet lab: is an IACUC needed? Response to protocol review scenario:
      agriculture exemption.

PMID- 16582890
TI  - Conference wet lab: is an IACUC needed?

PMID- 16582891
TI  - Conference wet lab: is an IACUC needed? Response to protocol review scenario:
      satellite situation.

PMID- 16582892
TI  - Conference wet lab: is an IACUC needed? Response to protocol review scenario:
      convene a committee.

PMID- 16582893
TI  - Conference wet lab: is an IACUC needed? Response to protocol review scenario: a
      word from OLAW and USDA.

PMID- 16582894
TI  - Intermittent inappetence and fur loss in a New Zealand White rabbit.

PMID- 16582896
TI  - Diagnostic cystocentesis: technique and considerations.
AB  - Cystocentesis, the aspiration of urine from the urinary bladder, has both
      diagnostic and therapeutic uses. This month, we discuss the diagnostic reasons
      for using this technique and summarize the steps necessary to safely perform the
      procedure in laboratory animals.

PMID- 16582897
TI  - Management of unanticipated outcomes in transgenic mouse facilities.
AB  - Experimental manipulations of rodents may result in unexpected adverse phenotypes
      that present problems from both regulatory and animal care-veterinary
      perspectives. The authors discuss the implications of unanticipated outcomes and
      describe a cage card-based tracking system used at the Harvard Medical School for
      the early detection and handling of unanticipated phenotypes in genetically
      altered rodents.

PMID- 16582898
TI  - Capture, care, and captive breeding of 13-lined ground squirrels, Spermophilus
      tridecemlineatus.
AB  - Researchers use the 13-lined ground squirrel for studies of hibernation
      biochemistry and physiology, as well as for modeling a variety of potential
      biomedical applications of hibernation physiology. It is currently necessary to
      capture research specimens from the wild; this presents a host of unknown
      variables, not least of which is the stress of captivity. Moreover, many
      investigators are unfamiliar with the husbandry of this species. The authors
      describe practical methods for their capture, year-round care (including
      hibernation), captive mating, and rearing of the young. These practices will
      allow the researcher to better standardize his or her population of research
      animals, optimizing the use of this interesting model organism.

PMID- 16582899
TI  - Individually ventilated caging system for effective allergen control.
AB  - The Type II Long IVC system is a versatile individually ventilated caging system
      with European Style Type II Long cages. The system works in both positive and
      negative pressure modes and HEPA filters both supply and exhaust air. The
      Institute of Occupational Medicine recently tested this product and found it to
      be effective in containing allergens in both positive and negative pressure
      modes.

PMID- 16582901
TI  - A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function.
AB  - Antigen stimulation of immune cells triggers Ca2+ entry through Ca2+ release
      activated Ca2+ (CRAC) channels, promoting the immune response to pathogens by
      activating the transcription factor NFAT. We have previously shown that cells
      from patients with one form of hereditary severe combined immune deficiency
      (SCID) syndrome are defective in store-operated Ca2+ entry and CRAC channel
      function. Here we identify the genetic defect in these patients, using a
      combination of two unbiased genome-wide approaches: a modified linkage analysis
      with single-nucleotide polymorphism arrays, and a Drosophila RNA interference
      screen designed to identify regulators of store-operated Ca2+ entry and NFAT
      nuclear import. Both approaches converged on a novel protein that we call Orai1,
      which contains four putative transmembrane segments. The SCID patients are
      homozygous for a single missense mutation in ORAI1, and expression of wild-type
      Orai1 in SCID T cells restores store-operated Ca2+ influx and the CRAC current
      (I(CRAC)). We propose that Orai1 is an essential component or regulator of the
      CRAC channel complex.

PMID- 16582902
TI  - Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR
      dependent long-term depression.
AB  - Drugs of abuse induce long-lasting changes in neural circuits that may underlie
      core components of addiction. Here we focus on glutamatergic synapses onto
      dopamine (DA) neurons of the ventral tegmental area (VTA). Using an 'ex vivo'
      approach in mice, we show that a single injection of cocaine caused strong
      rectification and conferred sensitivity to the polyamine Joro spider toxin (JST)
      of AMPAR-mediated excitatory postsynaptic currents (AMPAR EPSCs), indicating the
      recruitment of receptors that lack GluR2. This qualitative change in transmission
      was paralleled by an increase in the AMPAR:NMDAR ratio and was prevented by
      interfering with the protein interacting with C kinase-1 (PICK1) in vivo.
      Activation of metabotropic glutamate receptors (mGluR1s) by intraperitoneal
      injection of a positive modulator depotentiated synapses and abolished
      rectification in slices of cocaine-treated mice, revealing a mechanism to reverse
      cocaine-induced synaptic plasticity in vivo.

PMID- 16582903
TI  - Genetic mosaic with dual binary transcriptional systems in Drosophila.
AB  - MARCM (mosaic analysis with a repressible cell marker) involves specific labeling
      of GAL80-minus and GAL4-positive homozygous cells in otherwise heterozygous
      tissues. Here we demonstrate how the concurrent use of two independent binary
      transcriptional systems may facilitate complex MARCM studies in the Drosophila
      nervous system. By fusing LexA with the VP16 acidic activation domain (VP16) or
      the GAL4 activation domain (GAD), we obtained both GAL80-insensitive and GAL80
      suppressible transcriptional factors. LexA::VP16 can mediate MARCM-independent
      binary transgene induction in mosaic organisms. The incorporation of LexA::GAD
      into MARCM, which we call dual-expression-control MARCM, permits the induction of
      distinct transgenes in different patterns among GAL80-minus cells in mosaic
      tissues. Lineage analysis with dual-expression-control MARCM suggested the
      presence of neuroglioblasts in the developing optic lobes but did not indicate
      the production of glia by postembryonic mushroom body neuronal precursors. In
      addition, dual-expression-control MARCM with a ubiquitous LexA::GAD driver
      revealed many unidentified cells in the GAL4-GH146-positive projection neuron
      lineages.

PMID- 16582904
TI  - Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal
      long-term potentiation.
AB  - Postnatal glutamatergic principal neuron synapses are typically presumed to
      express only calcium-impermeable (CI), GluR2-containing AMPARs under
      physiological conditions. Here, however, we demonstrate that long-term
      potentiation (LTP) in CA1 hippocampal pyramidal neurons causes rapid
      incorporation of GluR2-lacking calcium-permeable (CP)-AMPARs: CP-AMPARs are
      present transiently, being replaced by GluR2-containing AMPARs approximately 25
      min after LTP induction. Thus, CP-AMPARs are physiologically expressed at CA1
      pyramidal cell synapses during LTP, and may be required for LTP consolidation.

PMID- 16582905
TI  - Activity-dependent regulation of inhibitory synaptic transmission in hippocampal
      neurons.
AB  - Neural activity regulates the number and properties of GABAergic synapses in the
      brain, but the mechanisms underlying these changes are unclear. We found that
      blocking spike activity globally in developing hippocampal neurons from rats
      reduced the density of GABAergic terminals as well as the frequency and amplitude
      of miniature inhibitory postsynaptic currents (mIPSCs). Chronic inactivity later
      in development led to a reduction in the mIPSC amplitude, without any change in
      GABAergic synapse density. By contrast, hyperpolarizing or abolishing spike
      activity in single neurons did not alter GABAergic synaptic inputs. Suppressing
      activity in individual presynaptic GABAergic neurons also failed to decrease
      synaptic output. Our results indicate that GABAergic synapses are regulated by
      the level of activity in surrounding neurons. Notably, we found that the
      expression of GABAergic plasticity involves changes in the amount of
      neurotransmitter in individual vesicles.

PMID- 16582906
TI  - Effects of visual experience on activity-dependent gene regulation in cortex.
AB  - There are critical periods in development when sensory experience directs the
      maturation of synapses and circuits within neocortex. We report that the critical
      period in mouse visual cortex has a specific molecular logic of gene regulation.
      Four days of visual deprivation regulated one set of genes during the critical
      period, and different sets before or after. Dark rearing perturbed the regulation
      of these age-specific gene sets. In addition, a 'common gene set', comprised of
      target genes belonging to a mitogen-activated protein (MAP) kinase signaling
      pathway, was regulated by vision at all ages but was impervious to prior history
      of sensory experience. Together, our results demonstrate that vision has dual
      effects on gene regulation in visual cortex and that sensory experience is needed
      for the sequential acquisition of age-specific, but not common, gene sets. Thus,
      a dynamic interplay between experience and gene expression drives activity
      dependent circuit maturation.

PMID- 16582907
TI  - Systematic identification of human mitochondrial disease genes through
      integrative genomics.
AB  - The majority of inherited mitochondrial disorders are due to mutations not in the
      mitochondrial genome (mtDNA) but rather in the nuclear genes encoding proteins
      targeted to this organelle. Elucidation of the molecular basis for these
      disorders is limited because only half of the estimated 1,500 mitochondrial
      proteins have been identified. To systematically expand this catalog, we
      experimentally and computationally generated eight genome-scale data sets, each
      designed to provide clues as to mitochondrial localization: targeting sequence
      prediction, protein domain enrichment, presence of cis-regulatory motifs, yeast
      homology, ancestry, tandem-mass spectrometry, coexpression and transcriptional
      induction during mitochondrial biogenesis. Through an integrated analysis we
      expand the collection to 1,080 genes, which includes 368 novel predictions with a
      10% estimated false prediction rate. By combining this expanded inventory with
      genetic intervals linked to disease, we have identified candidate genes for eight
      mitochondrial disorders, leading to the discovery of mutations in MPV17 that
      result in hepatic mtDNA depletion syndrome. The integrative approach promises to
      better define the role of mitochondria in both rare and common human diseases.

PMID- 16582908
TI  - BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS
      locus.
AB  - Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy. Although
      nine BBS genes have been cloned, they explain only 40-50% of the total mutational
      load. Here we report a major new BBS locus, BBS10, that encodes a previously
      unknown, rapidly evolving vertebrate-specific chaperonin-like protein. We found
      BBS10 to be mutated in about 20% of an unselected cohort of families of various
      ethnic origins, including some families with mutations in other BBS genes,
      consistent with oligogenic inheritance. In zebrafish, mild suppression of bbs10
      exacerbated the phenotypes of other bbs morphants.

PMID- 16582909
TI  - Magnitude and distribution of linkage disequilibrium in population isolates and
      implications for genome-wide association studies.
AB  - The genome-wide distribution of linkage disequilibrium (LD) determines the
      strategy for selecting markers for association studies, but it varies between
      populations. We assayed LD in large samples (200 individuals) from each of 11
      well-described population isolates and an outbred European-derived sample, using
      SNP markers spaced across chromosome 22. Most isolates show substantially higher
      levels of LD than the outbred sample and many fewer regions of very low LD
      (termed 'holes'). Young isolates known to have had relatively few founders show
      particularly extensive LD with very few holes; these populations offer
      substantial advantages for genome-wide association mapping.

PMID- 16582910
TI  - MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile
      hepatic mitochondrial DNA depletion.
AB  - The mitochondrial (mt) DNA depletion syndromes (MDDS) are genetic disorders
      characterized by a severe, tissue-specific decrease of mtDNA copy number, leading
      to organ failure. There are two main clinical presentations: myopathic (OMIM
      609560) and hepatocerebral (OMIM 251880). Known mutant genes, including TK2,
      SUCLA2, DGUOK and POLG, account for only a fraction of MDDS cases. We found a new
      locus for hepatocerebral MDDS on chromosome 2p21-23 and prioritized the genes on
      this locus using a new integrative genomics strategy. One of the top-scoring
      candidates was the human ortholog of the mouse kidney disease gene Mpv17. We
      found disease-segregating mutations in three families with hepatocerebral MDDS
      and demonstrated that, contrary to the alleged peroxisomal localization of the
      MPV17 gene product, MPV17 is a mitochondrial inner membrane protein, and its
      absence or malfunction causes oxidative phosphorylation (OXPHOS) failure and
      mtDNA depletion, not only in affected individuals but also in Mpv17-/- mice.

PMID- 16582911
TI  - NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and
      phosphatidylinositol-3-kinase in human natural killer cells.
AB  - NKG2D is an important immunosurveillance receptor that responds to stress-induced
      ligand expression on tumors and virus-infected cells. Human natural killer cells
      express NKG2D and require the transmembrane adaptor DAP10 to initiate their full
      cytotoxic activation. However, DAP10 has no immunoreceptor tyrosine-based
      activation motif and thus the mechanism of recruiting 'downstream' effector
      proteins is unclear. We show here that binding of the p85 subunit of
      phosphatidylinositol-3- kinase to DAP10 could not by itself trigger cell-mediated
      cytotoxicity and that binding of an intermediate consisting of the DAP10 binding
      partner Grb2 and the effector molecule Vav1 (Grb2-Vav1) to DAP10 was sufficient
      to initiate tyrosine-phosphorylation events. For full calcium release and
      cytotoxicity to occur, both Grb2-Vav1 and p85 had to bind to DAP10. These
      findings identify a previously unknown mechanism by which NKG2D-DAP10 mediates
      cytotoxicity and provides a framework for evaluating activation by other receptor
      complexes that lack immunoreceptor tyrosine-based activation motifs.

PMID- 16582912
TI  - A unique function for cyclin D3 in early B cell development.
AB  - During hematopoiesis, stem cell proliferation is dependent on expression of the D
      type cyclins. However, little is known about how each cyclin D contributes to the
      development of specific hematopoietic lineages. Here, analysis of Ccnd1(-/-),
      Ccnd2(-/-), Ccnd3(-/-) and Ccnd2(-/-)Ccnd3(-/-) mice showed that cyclin D3 was
      uniquely required for the development of pre-B cells. Transcription of Ccnd3 was
      dependent on expression of the common gamma-chain. In contrast, expression of the
      pre-B cell receptor and activation of 'downstream' signaling pathways prevented
      proteasome-mediated degradation of cyclin D3. Cyclin D3 has a key function in B
      cell development by integrating cytokine and pre-B cell receptor-dependent
      signals to expand the pool of pre-B cells that have successfully rearranged
      immunoglobulin heavy chain.

PMID- 16582913
TI  - CD8+ recent thymic emigrants home to and efficiently repopulate the small
      intestine epithelium.
AB  - Prevailing knowledge dictates that naive alphabeta T cells require activation in
      lymphoid tissues before differentiating into effector or memory T cells capable
      of trafficking to nonlymphoid tissues. Here we demonstrate that CD8(+) recent
      thymic emigrants (RTEs) migrated directly into the small intestine. CCR9, CCL25
      and alpha(4)beta(7) integrin were required for gut entry of CD8(+) RTEs. After T
      cell receptor stimulation, intestinal CD8(+) RTEs proliferated and acquired a
      surface phenotype resembling that of intraepithelial lymphocytes. CD8(+) RTEs
      efficiently populated the gut of lymphotoxin-alpha-deficient mice, which lack
      lymphoid organs. These studies challenge the present understanding of naive
      alphabeta T cell trafficking and suggest that RTEs may be involved in maintaining
      a diverse immune repertoire at mucosal surfaces.

PMID- 16582914
TI  - Local density of states effects at the metal-molecule interfaces in a molecular
      device.
AB  - Clarifying the nature of interactions between metal electrodes and organic
      molecules still represent one of the challenging problems in molecular
      electronics that needs to be solved in order to optimize electron transport
      through a molecular device. For this purpose, electronic properties at metal
      molecule interfaces were studied by combining experimental and theoretical
      methods. Applying a novel electrochemical approach, strictly two-dimensional Pd
      islands were prepared on top of 4-mercaptopyridine self-assembled monolayers (4MP
      SAMs) which, in turn, were deposited on (111)-oriented Au single crystals.
      Electron spectroscopy together with density functional theory calculations
      revealed strong interactions between the molecules and the islands due to Pd-N
      bonds, resulting in a drastically reduced density of states (DOS) at the Fermi
      level EF for a nearly closed Pd monolayer, and even non-metallic properties for
      nanometre-sized islands. Similarly, a significantly reduced DOS at EF was
      observed for the topmost Au layer at the Au-SAM interface due to Au-S
      interactions, suggesting that these effects are rather general.

PMID- 16582915
TI  - Engineered heart tissue grafts improve systolic and diastolic function in
      infarcted rat hearts.
AB  - The concept of regenerating diseased myocardium by implantation of tissue
      engineered heart muscle is intriguing, but convincing evidence is lacking that
      heart tissues can be generated at a size and with contractile properties that
      would lend considerable support to failing hearts. Here we created large
      (thickness/diameter, 1-4 mm/15 mm), force-generating engineered heart tissue from
      neonatal rat heart cells. Engineered heart tissue formed thick cardiac muscle
      layers when implanted on myocardial infarcts in immune-suppressed rats. When
      evaluated 28 d later, engineered heart tissue showed undelayed electrical
      coupling to the native myocardium without evidence of arrhythmia induction.
      Moreover, engineered heart tissue prevented further dilation, induced systolic
      wall thickening of infarcted myocardial segments and improved fractional area
      shortening of infarcted hearts compared to controls (sham operation and
      noncontractile constructs). Thus, our study provides evidence that large
      contractile cardiac tissue grafts can be constructed in vitro, can survive after
      implantation and can support contractile function of infarcted hearts.

PMID- 16582916
TI  - Correction of X-linked chronic granulomatous disease by gene therapy, augmented
      by insertional activation of MDS1-EVI1, PRDM16 or SETBP1.
AB  - Gene transfer into hematopoietic stem cells has been used successfully for
      correcting lymphoid but not myeloid immunodeficiencies. Here we report on two
      adults who received gene therapy after nonmyeloablative bone marrow conditioning
      for the treatment of X-linked chronic granulomatous disease (X-CGD), a primary
      immunodeficiency caused by a defect in the oxidative antimicrobial activity of
      phagocytes resulting from mutations in gp91(phox). We detected substantial gene
      transfer in both individuals' neutrophils that lead to a large number of
      functionally corrected phagocytes and notable clinical improvement. Large-scale
      retroviral integration site-distribution analysis showed activating insertions in
      MDS1-EVI1, PRDM16 or SETBP1 that had influenced regulation of long-term
      hematopoiesis by expanding gene-corrected myelopoiesis three- to four-fold in
      both individuals. Although insertional influences have probably reinforced the
      therapeutic efficacy in this trial, our results suggest that gene therapy in
      combination with bone marrow conditioning can be successfully used to treat
      inherited diseases affecting the myeloid compartment such as CGD.

PMID- 16582917
TI  - Monolayered mesenchymal stem cells repair scarred myocardium after myocardial
      infarction.
AB  - Mesenchymal stem cells are multipotent cells that can differentiate into
      cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet
      technology, that monolayered mesenchymal stem cells have multipotent and self
      propagating properties after transplantation into infarcted rat hearts. We
      cultured adipose tissue-derived mesenchymal stem cells characterized by flow
      cytometry using temperature-responsive culture dishes. Four weeks after coronary
      ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred
      myocardium. After transplantation, the engrafted sheet gradually grew to form a
      thick stratum that included newly formed vessels, undifferentiated cells and few
      cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine
      pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered
      mesenchymal stem cells reversed wall thinning in the scar area and improved
      cardiac function in rats with myocardial infarction. Thus, transplantation of
      monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac
      tissue regeneration.

PMID- 16582920
TI  - Nanomedicine: a matter of rhetoric?

PMID- 16582919
TI  - Functional epitopes at the ribosome subunit interface.
AB  - The ribosome is a 2.5-MDa molecular machine that synthesizes cellular proteins
      encoded in mRNAs. The 30S and 50S subunits of the ribosome associate through
      structurally defined intersubunit bridges burying 6,000 A(2), 80% of which is
      buried in conserved RNA-RNA interactions. Intersubunit bridges bind translation
      factors, may coordinate peptide bond formation and translocation and may be
      actively remodeled in the post-termination complex, but the functional importance
      of numerous 30S bridge nucleotides had been unknown. We carried out large-scale
      combinatorial mutagenesis and in vivo selections on 30S nucleotides that form RNA
      RNA intersubunit bridges in the Escherichia coli ribosome. We determined the
      covariation and functional importance of bridge nucleotides, allowing comparison
      of the structural interface and phylogenetic data to the functional epitope. Our
      results reveal how information for ribosome function is partitioned across
      bridges, and suggest a subset of nucleotides that may have measurable effects on
      individual steps of the translational cycle.

PMID- 16582918
TI  - Induction of leptin resistance through direct interaction of C-reactive protein
      with leptin.
AB  - The mechanisms underlying leptin resistance are still being defined. We report
      here the presence in human blood of several serum leptin-interacting proteins
      (SLIPs), isolated by leptin-affinity chromatography and identified by mass
      spectrometry and immunochemical analysis. We confirmed that one of the major
      SLIPs is C-reactive protein (CRP). In vitro, human CRP directly inhibits the
      binding of leptin to its receptors and blocks its ability to signal in cultured
      cells. In vivo, infusion of human CRP into ob/ob mice blocked the effects of
      leptin upon satiety and weight reduction. In mice that express a transgene
      encoding human CRP, the actions of human leptin were completely blunted. We also
      found that physiological concentrations of leptin can stimulate expression of CRP
      in human primary hepatocytes. Recently, human CRP has been correlated with
      increased adiposity and plasma leptin. Thus, our results suggest a potential
      mechanism contributing to leptin resistance, by which circulating CRP binds to
      leptin and attenuates its physiological functions.

PMID- 16582921
TI  - Nanohazards: knowledge is our first defence.

PMID- 16582923
TI  - Perovskites: is the ultimate memory in sight?

PMID- 16582924
TI  - Crystal deformation: colloid model for atoms.

PMID- 16582925
TI  - Quantum information: long live the spin.

PMID- 16582926
TI  - Material witness: sonic sense.

PMID- 16582927
TI  - Superconductivity: conveyor belts for magnetic flux quanta.

PMID- 16582928
TI  - Two-dimensional crystallization: express nanoparticle ordering.

PMID- 16582929
TI  - Plasmodium post-genomics: better the bug you know?
AB  - Since the publication of the sequence of the genome of Plasmodium falciparum, the
      major causative agent of human malaria, many post-genomic studies have been
      completed. Invaluably, these data can now be analysed comparatively owing to the
      availability of a significant amount of genome-sequence data from several closely
      related model species of Plasmodium and accompanying global proteome and
      transcriptome studies. This review summarizes our current knowledge and how this
      has already been--and will continue to be--exploited in the search for vaccines
      and drugs against this most significant infectious disease of the tropics.

PMID- 16582930
TI  - Exploiting pathogenic Escherichia coli to model transmembrane receptor
      signalling.
AB  - Many microbial pathogens manipulate the actin cytoskeleton of eukaryotic target
      cells to promote their internalization, intracellular motility and dissemination.
      Enteropathogenic and enterohaemorrhagic Escherichia coli, which both cause severe
      diarrhoeal disease, can adhere to mammalian intestinal cells and induce
      reorganization of the actin cytoskeleton into 'pedestal-like' pseudopods beneath
      the extracellular bacteria. As pedestal assembly is triggered by E. coli
      virulence factors that mimic several host cell-signalling components, such as
      transmembrane receptors, their cognate ligands and cytoplasmic adaptor proteins,
      it can serve as a powerful model system to study eukaryotic transmembrane
      signalling. Here, we consider the impact of recent data on our understanding of
      both E. coli pathogenesis and cell biology, and the rich prospects for exploiting
      these bacterial factors as versatile tools to probe cellular signalling pathways.

PMID- 16582931
TI  - Parallels among positive-strand RNA viruses, reverse-transcribing viruses and
      double-stranded RNA viruses.
AB  - Viruses are divided into seven classes on the basis of differing strategies for
      storing and replicating their genomes through RNA and/or DNA intermediates.
      Despite major differences among these classes, recent results reveal that the non
      virion, intracellular RNA-replication complexes of some positive-strand RNA
      viruses share parallels with the structure, assembly and function of the
      replicative cores of extracellular virions of reverse-transcribing viruses and
      double-stranded RNA viruses. Therefore, at least four of seven principal virus
      classes share several underlying features in genome replication and might have
      emerged from common ancestors. This has implications for virus function,
      evolution and control.

PMID- 16582932
TI  - The metabotropic glutamate receptor 4 is internalized and desensitized upon
      protein kinase C activation.
AB  - 1. The metabotropic glutamate receptor 4 (mGluR4) is a Galphai-coupled receptor
      that modulates glutamatergic neurotransmission. As mGluR4 expression and
      activation have been implicated in a number of pathological conditions and
      because the internalization and desensitization properties of this receptor are
      poorly understood, studies were designed to investigate these aspects of mGluR4
      biology. 2. Neither agonist activation by L-(+)-2-amino-4-phosphonobutyric acid
      (L-AP4) nor L-glutamate caused mGluR4 internalization when cmyc-tagged mGluR4 was
      expressed in a human embryonic kidney 293 cell line as assessed by cell surface
      enzyme-linked immunosorbent and immunostaining assays. Instead, a modest increase
      in mGluR4 surface expression was observed and found to be receptor specific as
      the competitive antagonist alpha-cyclopropyl-4-phosphonophenylglycine (CPPG)
      blocked this effect. 3. In contrast, mGluR4 internalized when the protein kinase
      C (PKC) pathway was activated either by phorbol-12-myristate-13-acetate (PMA) or
      by the activation of the Galphaq-coupled, neurokinin 3 receptor (NK3R) when co
      expressed. This process was PKC-dependent as the specific PKC inhibitor GF
      109203X inhibited PMA and NK3R-mediated internalization. 4. PKC activation by PMA
      caused desensitization of mGluR4 as measured by forskolin-stimulated cAMP
      inhibition, whereas agonist activation had no effect on desensitization. 5. When
      mGluR4's coupling was redirected from adenylyl cyclase to phospholipase C by
      coexpression of a chimeric Galphaqo5 protein, mGluR4 both internalized and
      desensitized in response to its agonists. 6. These findings demonstrate that
      mGluR4 internalization and desensitization are agonist-independent unless
      pathways leading to the activation of PKC are induced.

PMID- 16582933
TI  - Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in
      the MPTP model of Parkinson's disease by activation of adenosine A1 receptor.
AB  - 1. This study examined whether Paeoniflorin (PF), the major active components of
      Chinese herb Paeoniae alba Radix, has neuroprotective effect in the 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD).
      2. Subcutaneous administration of PF (2.5 and 5 mg kg(-1)) for 11 days could
      protect tyrosine hydroxylase (TH)-positive substantia nigra neurons and striatal
      nerve fibers from death and bradykinesia induced by four-dose injection of MPTP
      (20 mg kg(-1)) on day 8. 3. When given at 1 h after the last dose of MPTP, and
      then administered once a day for the following 3 days, PF (2.5 and 5 mg kg(-1))
      also significantly attenuated the dopaminergic neurodegeneration in a dose
      dependent manner. Post-treatment with PF (5 mg kg(-1)) significantly attenuated
      MPTP-induced proinflammatory gene upregulation and microglial and astrocytic
      activation. 4. Pretreatment with 0.3 mg kg(-1) 8-cyclopentyl-1,3
      dipropylxanthine, an adenosine A1 receptor (A1AR) antagonist, 15 min before each
      dose of PF, reversed the neuroprotective and antineuroinflammatory effects of PF.
      5. In conclusion, this study demonstrated that PF could reduce the MPTP-induced
      toxicity by inhibition of neuroinflammation by activation of the A1AR, and
      suggested that PF might be a valuable neuroprotective agent for the treatment of
      PD.

PMID- 16582934
TI  - Spinal alpha(2)-adrenergic and muscarinic receptors and the NO release cascade
      mediate supraspinally produced effectiveness of gabapentin at decreasing
      mechanical hypersensitivity in mice after partial nerve injury.
AB  - After partial nerve injury, the central analgesic effect of systemically
      administered gabapentin is mediated by both supraspinal and spinal actions. We
      further evaluate the mechanisms related to the supraspinally mediated analgesic
      actions of gabapentin involving the descending noradrenergic system.
      Intracerebroventricularly (i.c.v.) administered gabapentin (100 microg) decreased
      thermal and mechanical hypersensitivity in a murine chronic pain model that was
      prepared by partial ligation of the sciatic nerve. These effects were abolished
      by intrathecal (i.t.) injection of either yohimbine (3 microg) or idazoxan (3
      microg), alpha(2)-adrenergic receptor antagonists. Pretreatment with atropine
      (0.3 mg kg(-1), i.p. or 0.1 microg, i.t.), a muscarinic receptor antagonist,
      completely suppressed the effect of i.c.v.-injected gabapentin on mechanical
      hypersensitivity, whereas its effect on thermal hypersensitivity remained
      unchanged. Similar effects were obtained with pirenzepine (0.1 microg, i.t.), a
      selective M(1)-muscarinic receptor antagonist, but not with methoctramine (0.1
      and 0.3 microg, i.t.), a selective M(2)-muscarinic receptor antagonist. The
      cholinesterase inhibitor neostigmine (0.3 ng, i.t.) potentiated only the
      analgesic effect of i.c.v. gabapentin on mechanical hypersensitivity, confirming
      spinal acetylcholine release downstream of the supraspinal action of gabapentin.
      Moreover, the effect of i.c.v. gabapentin on mechanical but not thermal
      hypersensitivity was reduced by i.t. injection of L-NAME (3 microg) or L-NMMA (10
      microg), both of which are nitric oxide (NO) synthase inhibitors. Systemically
      administered naloxone (10 mg kg(-1), i.p.), an opioid receptor antagonist, failed
      to suppress the analgesic actions of i.c.v. gabapentin, indicating that opioid
      receptors are not involved in activation of the descending noradrenergic system
      by gabapentin. Thus, the supraspinally mediated effect of gabapentin on
      mechanical hypersensitivity involves activation of spinal alpha(2)-adrenergic
      receptors followed by muscarinic receptors (most likely M(1)) and the NO cascade.
      In contrast, the effect of supraspinal gabapentin on thermal hypersensitivity is
      independent of the spinal cholinergic-NO system.

PMID- 16582938
TI  - Evidence-based medicine: applied science?

PMID- 16582935
TI  - Heterogeneous CPA sensitivity of spontaneous excitation in smooth muscle of the
      rabbit urethra.
AB  - 1. To investigate the role of intracellular Ca stores in generating spontaneous
      excitation of the urethra, the effects of cyclopiazonic acid (CPA) on spontaneous
      contractions, transient increases in intracellular calcium concentration
      ([Ca2+]i; Ca transients) and depolarizations were examined in smooth muscles of
      the rabbit urethra. 2. In about 90% of circular smooth muscle (CSM) preparations,
      CPA (10 microM) increased the amplitude of spontaneous contractions by about 180%
      and reduced their frequency to some 25% of control values (CPA-resistant), while
      it readily abolished the contractions in the remaining preparations. 3. In about
      70% of CSM preparations, CPA prevented the generation of spontaneous
      depolarizations termed slow waves, but increased their amplitude and duration in
      the remainder. CPA also prevented the generation of spontaneous Ca transients in
      about 40% of CSM preparations, while increasing their amplitude and duration in
      the remaining preparations. In CPA-resistant preparations that had been exposed
      to nicardipine (1 microM), subsequent CPA invariably abolished residual
      spontaneous depolarizations or Ca transients. CPA abolished caffeine-induced Ca
      transients in Ca-free solutions, suggesting that it effectively depleted
      intracellular Ca stores. 4. Longitudinal smooth muscles generated spontaneous
      action potentials, which had a shape distinct from that of slow waves in CSM.
      Spontaneous action potentials were abolished by nicardipine but not CPA. 5.
      Transmural nerve stimulation increased the frequency of Ca transients to give a
      sustained rise in [Ca2+]i, but inhibited their generation after blocking alpha
      adrenoceptors with phentolamine (1 microM). These nerve-evoked responses were
      preserved in preparations that had been exposed to CPA. Similarly, both in
      control and CPA-treated CSM preparations, spontaneous Ca transients were
      accelerated by noradrenaline (NAd, 1 microM) and were suppressed by 3-morpholino
      sydnonimine (SIN-1, 10 microM), a nitric oxide (NO) donor. 6. In conclusion, CSM
      of the urethra generates spontaneous activity, which depends on Ca release from
      intracellular Ca stores. However, after blocking this primary pacemaking
      mechanism, L-type Ca channel-dependent action potentials may drive CSM.
      Irrespective of the origin of pacemaking, neurally-released NAd and NO are
      capable of modulating spontaneous excitation.

PMID- 16582936
TI  - Regulation of ERK1/2 activity by ghrelin-activated growth hormone secretagogue
      receptor 1A involves a PLC/PKCvarepsilon pathway.
AB  - 1. The growth hormone secretagogue receptor 1a (GHSR-1a) is a G-protein coupled
      receptor, involved in the biological actions of ghrelin by triggering inositol
      phosphates and calcium intracellular second messengers. It has also been reported
      that ghrelin could activate the 44- and 42-kDa extracellular signal-regulated
      protein kinases (ERK1/2) in different cell lines, but it is not clear whether
      this regulation is GHSR-1a dependent or not. 2. To provide direct evidence for
      the coupling of GHSR-1a to ERK1/2 activation, this pathway has been studied in a
      heterologous expression system. 3. Thus, in Chinese hamster ovary (CHO) cells we
      showed that ghrelin induced, via the human GHSR-1a, a transient and dose
      dependent activation of ERK1/2 leading to activation of the transcriptional
      factor Elk1. 4. We then investigated the precise mechanisms involved in GHSR-1a
      mediated ERK1/2 activation using various specific inhibitors and dominant
      negative mutants and found that internalization of GHSR-1a was not necessary. Our
      results also indicate that phospholipase C (PLC) was involved in GHSR-1a-mediated
      ERK1/2 activation, however, pathways like tyrosine kinases, including Src, and
      phosphoinositide 3-kinases were not found to be involved. GHSR-1a-mediated ERK1/2
      activation was abolished both by a general protein kinase C (PKC) inhibitor,
      Go6983, and by PKC depletion using overnight pretreatment with phorbol ester.
      Moreover, the calcium chelator, BAPTA-AM, and the inhibitor of conventional PKCs,
      Go6976, had no effect on the GHSR-1a-mediated ERK1/2 activation, suggesting the
      involvement of novel PKC isoforms (epsilon, delta), but not conventional or
      atypical PKCs. Further analyses suggest that PKCepsilon is required for the
      activation of ERK1/2. 5. Taken together, these data suggest that ghrelin, through
      GHSR-1a, activates the Elk1 transcriptional factor and ERK1/2 by a PLC- and
      PKCepsilon-dependent pathway.

PMID- 16582939
TI  - Hemochromatosis case definition: out of focus?

PMID- 16582940
TI  - Alternative and complementary therapies for inflammatory bowel disease.

PMID- 16582956
TI  - Where is the optimal location for paracentesis?

PMID- 16582958
TI  - Can growth hormone and glutamine reduce parenteral nutrition requirements in
      patients with short-bowel syndrome?

PMID- 16582959
TI  - How effective is fluoxetine for the treatment of pain and constipation
      predominant irritable bowel syndrome?

PMID- 16582957
TI  - Is fiber beneficial for the treatment of hemorrhoids?

PMID- 16582960
TI  - Is biofeedback therapy an effective treatment for patients with constipation?

PMID- 16582961
TI  - How effective is endoscopic ultrasound-guided biopsy?

PMID- 16582962
TI  - Nutritional support in patients with chronic liver disease.
AB  - Malnutrition is highly prevalent among patients with chronic liver disease and is
      nearly universal among patients awaiting liver transplantation. Malnutrition in
      patients with cirrhosis leads to increased morbidity and mortality rates.
      Furthermore, patients who are severely malnourished before transplant surgery
      have a higher rate of complications and a decreased overall survival rate after
      liver transplantation. In light of the high incidence of malnutrition among
      patients with chronic liver disease and the complications that result from
      malnutrition in these patients, it is essential to assess the nutritional status
      of all patients with liver disease, and to initiate treatment as indicated. This
      review addresses the etiologies of malnutrition, methods used to assess
      nutritional status, and appropriate treatment strategies.

PMID- 16582963
TI  - Technology insight: The role of impedance testing for esophageal disorders.
AB  - Classic techniques like videofluoroscopy, stationary manometry, and ambulatory 24
      h pH-metry are routinely used in the clinic to study patients with dysphagia,
      chest pain and reflux-related symptoms. Although these techniques have been very
      useful over the years, both for diagnosis and for therapeutic guidance, there are
      still many patients with dysphagia or chest pain who remain undiagnosed even
      after testing, and patients with typical and atypical symptoms of
      gastroesophageal reflux disease, with normal pH-metry findings, who do not
      respond adequately to antisecretory therapy. Esophageal impedance monitoring is a
      new technique that can be used alone and in combination with pH-metry and
      manometry to evaluate bolus transport and all types of gastroesophageal reflux
      (acid and nonacid). This review describes the esophageal impedance monitoring
      technique and summarizes the published validation studies that compare impedance
      monitoring with other methods, as well as normal values and reproducibility of
      impedance patterns and their association with symptoms.

PMID- 16582964
TI  - Drug insight: antagonists of tumor-necrosis factor-alpha in the treatment of
      inflammatory bowel disease.
AB  - In the past decade, advances in the understanding of the pathogenesis of
      inflammatory bowel disease have permitted the development of agents directed
      against rational therapeutic targets. In particular, various antagonists of tumor
      necrosis factor-alpha have been developed. These include infliximab, adalimumab,
      certolizumab (CDP870), CDP571, etanercept, and onercept. Clinical trials of these
      agents have demonstrated varying degrees of clinical efficacy. The use of these
      agents can be limited by infection, immunogenicity, acute infusion reactions,
      delayed hypersensitivity reactions, and autoimmune phenomena. This review
      provides insights into the use of antagonists of tumor-necrosis factor-alpha for
      the treatment of inflammatory bowel disease.

PMID- 16582965
TI  - A patient with anemia of obscure origin: Crohn's disease in disguise.
AB  - BACKGROUND: A 65-year-old white Mediterranean male with a 10-year history of
      intermittent anemia, who was otherwise completely asymptomatic, was referred to
      our hospital in March 2004. He had a medical history of beta thalassemia and
      fecal occult blood tests had occasionally been positive. INVESTIGATIONS: Fecal
      occult blood test, laboratory investigations, esophagogastroduodenoscopy,
      colonoscopy with retrograde ileoscopy, mesenteric angiography, small-bowel
      series, CT scan of the abdomen and pelvis, Meckel's scan, and capsule endoscopy.
      Laparoscopic surgery followed by macroscopic and microscopic histopathologic
      examination of samples obtained during the procedure. DIAGNOSIS: Crohn's disease
      of the small bowel. MANAGEMENT: Laparoscopic segmental small-bowel resection with
      end-to-end anastomosis. Postsurgical treatment with Pentasa 4 g a day.

PMID- 16582967
TI  - An analysis of referees and referrals to a specialist concussion clinic in New
      Zealand.
AB  - AIM: This study reviews the characteristics of referrals to a specialist
      concussion clinic (Burwood Hospital Concussion Clinic, Christchurch, New Zealand)
      in its first two years of operation. METHOD: Information regarding referral
      source, demographic and clinical features, time since mild traumatic brain injury
      (MTBI), assessment and treatment provided, service follow-up, and outcome at
      discharge were collected from a file search of all referrals received in the two
      years ending in October 2004. RESULTS: Cases reflected the clinical and
      demographic diversity expected of those incurring an MTBI. Age and referral
      source were associated with failing to keep initial appointments. Assessments
      typically resulted in ongoing treatment from the service, although many were 'one
      off' assessments. One-in-five cases resulted in ongoing treatment for more than 7
      months. Gender, cause of MTBI, and time delay between injury and assessment were
      significantly associated with receiving long-term follow-up. Most cases had a
      good clinical outcome at discharge. CONCLUSIONS: While the Concussion Clinic
      services the intended clinical population, referrals for assault-related MTBIs
      were greater than expected, and men may be under-referred. The disproportional
      number of non-attending patients referred from Christchurch Hospital Emergency
      Department along with the unanticipated proportion of cases receiving long-term
      follow-up, suggest a need for review of the referral response systems and the
      scope of service provision.

PMID- 16582966
TI  - Nucleolin is involved in interferon regulatory factor-2-dependent transcriptional
      activation.
AB  - We have previously shown that interferon regulatory factor-2 (IRF-2) is
      acetylated in a cell growth-dependent manner, which enables it to contribute to
      the transcription of cell growth-regulated promoters. To clarify the function of
      acetylation of IRF-2, we investigated the proteins that associate with acetylated
      IRF-2. In 293T cells, the transfection of p300/CBP-associated factor (PCAF)
      enhanced the acetylation of IRF-2. In cells transfected with both IRF-2 and PCAF,
      IRF-2 associated with endogenous nucleolin, while in contrast, minimal
      association was observed when IRF-2 was transfected with a PCAF histone acetyl
      transferase (HAT) deletion mutant. In a pull-down experiment using stable
      transfectants, acetylation-defective mutant IRF-2 (IRF-2K75R) recruited nucleolin
      to a much lesser extent than wild-type IRF-2, suggesting that nucleolin
      preferentially associates with acetylated IRF-2. Nucleolin in the presence of
      PCAF enhanced IRF-2-dependent H4 promoter activity in NIH3T3 cells. Nucleolin
      knock-down using siRNA reduced the IRF-2/PCAF-mediated promoter activity.
      Chromatin immunoprecipitation analysis indicated that PCAF transfection increased
      nucleolin binding to IRF-2 bound to the H4 promoter. We conclude that nucleolin
      is recruited to acetylated IRF-2, thereby contributing to gene regulation crucial
      for the control of cell growth.

PMID- 16582968
TI  - Management of risk factors: a survey of New Zealand vascular surgeons.
AB  - AIM: Patients with peripheral occlusive arterial disease (POAD) suffer
      significant morbidity and mortality from cardiovascular events that may be
      reduced by appropriate risk factor management. The aim of this study was to
      document the opinion of New Zealand vascular surgeons regarding risk factor
      management in patients with POAD. METHODS: A questionnaire was emailed to 42 New
      Zealand vascular surgeons. Surgeons were asked if they checked risk factors in
      patients with POAD and who they thought should manage these risk factors. The
      survey was then re-emailed to non-responders after 3 weeks and subsequently
      posted to the remaining non-responders with a reply paid envelope after a further
      3 weeks. RESULTS: The overall response rate was 83% (35/42). Thirty-four of the
      35 surgeons (97%) stated that they routinely asked smoking history, 69% monitored
      blood pressure, 74% checked cholesterol level, 57% checked blood glucose level,
      and none checked homocysteine level, although 43% consider hyperhomocysteinaemia
      to be a risk factor for atherosclerosis. Vascular surgeons considered general
      practitioners should play a pivotal role in the management of cardiovascular risk
      factors. A variable proportion of vascular surgeons thought that the vascular
      team should also be involved in the management of smoking (46%), hyperlipidaemia
      (20%), hyperhomocysteinaemia (23%), and prescription of antiplatelet therapy
      (69%). CONCLUSIONS: Modification of risk factors in patients with POAD is
      imperative but opinion on who is responsible for risk factor management lacks
      consensus. It is more important that risk factor modification occurs than who
      oversees such intervention.

PMID- 16582970
TI  - Medical Image. An unusual cause of abdominal pain.

PMID- 16582969
TI  - A "fishy" cough: hepatobronchial fistula due to a pyogenic liver abscess.
AB  - A hepatobronchial fistula is an anatomic communication between the liver
      parenchyma and the bronchial tree. Major causes of such fistulae include
      inflammatory conditions resulting from obstruction of the biliary tract and
      infectious processes, such as pyogenic liver abscesses, amoebiasis, and hydatid
      cysts. We report a rare case of a patient (with a chronic, recurrent hepatic
      abscess) who suffered a persistent, productive cough resulting from a
      hepatobronchial fistula.

PMID- 16582971
TI  - Representative case series from New Zealand public hospital admissions in 1998-
      III: adverse events and death.
AB  - AIMS: To examine a representative series of adverse events in New Zealand public
      hospitals where death was the final outcome recorded, with a view to determining
      the relationship between adverse event and death. METHODS: A review was carried
      out of the 38 adverse events (AEs) in the New Zealand Quality of Healthcare Study
      where death was the outcome, and categories of relationship were established.
      These were identified from the total of 850 AEs determined by two-stage
      retrospective review of a representative sample of 6579 medical records drawn
      from 13 NZ public hospitals in 1998. A stricter definition of AEs, comparable
      with American studies, was then applied to estimate rates of death associated
      with AEs. RESULTS: There were 118 deaths at discharge identified in the sample of
      medical records, giving a rate of 18.0 deaths per 1000 admissions overall. A
      total of 30 deaths, either at or after discharge, were associated with AEs (4.6
      per 1000 admissions); 19 being judged attributable to the AE either "definitely"
      (10) or probably (9), giving a combined rate of 2.8 AE-attributable deaths per
      1000 admissions. The "definite" group had an age, comorbidity, and added-bed-days
      profile that was close to the average for all deaths associated with an AE. The
      "probable" group departed from this profile in being younger, exhibiting higher
      comorbidity, and having twice the added bed-days. Based on population life
      tables, the average years of life lost was 11.8 years for the definite group and
      25.0 years for the probable group. Assessed on the preventability of the
      associated AE, it was estimated that 2.2 deaths per 1000 admissions were highly
      preventable. However, once deaths that were not judged to be attributable to the
      AE were excluded, the rate reduced to 1.3 AE-preventable deaths per 1000.
      CONCLUSIONS: Because of the nature of the record review procedure used in the New
      Zealand Quality of Healthcare Study, a finding of death did not necessarily mean
      that an adverse event and death were causally related. Indeed, it is possible
      that extrapolations of mortality rates in this and other similar studies over
      estimate by about a half the number of deaths caused by healthcare management.

PMID- 16582972
TI  - Cutaneous larva migrans (hookworm) acquired in Christchurch, New Zealand.
AB  - A case of cutaneous larva migrans is presented. The patient acquired the parasite
      in a suburban Christchurch property. A biopsy confirmed the clinical diagnosis.
      Cutaneous larva migrans is common in returned travellers from the tropics. It is
      rare in New Zealand, however. Presumably there were very specific, favourable
      local factors to allow maturation and transmission of the larva in this case.

PMID- 16582973
TI  - Appropriate use of pagers in a New Zealand tertiary hospital.
AB  - AIMS: To identify the appropriateness of calls to on-call house officers in a
      major tertiary teaching hospital. METHODS: A prospective observational study was
      conducted at Auckland City Hospital over the months of June, July, and August
      2004. Fourteen house officers from a range of medical and surgical services
      categorised calls received while on-call after-hours into one of three groups:
      'appropriate and urgent'; 'appropriate but not urgent'; and 'inappropriate'.
      RESULTS: 844 calls were recorded and categorised, with approximately even
      distribution between medical services (431 calls) and surgical services (413
      calls); 30% of calls were deemed clinically appropriate and required a response
      within 1 hour; 53% of calls were deemed clinically appropriate but did not
      require a response within an hour; while 17% of calls were deemed inappropriate.
      CONCLUSIONS: The most important function an on-call house officer performs is
      responding to urgent medical situations. Frequent interruptions mean that house
      officers may become less efficient and more prone to making mistakes. The
      majority of calls received by on-call house officers did not need immediate
      responses and would have been better communicated via a less intrusive system
      such as text-messaging or the keeping of a non-urgent jobs list. If house
      officers were paged more appropriately then they would be interrupted less
      frequently and would be able to provide safer, more efficient, and timelier
      patient care.

PMID- 16582974
TI  - Frequency of calls to "on-call" house officer pagers at Auckland City Hospital,
      New Zealand.
AB  - AIMS: To quantify the number of calls made to specified on-call house officer
      pagers and to comment on possible implications for practice. METHODS: Seven on
      call pagers, covering a range of surgical and medical specialties at Auckland
      City Hospital, were identified. Data for a 4-month period from April to August
      2004 was recorded and analysed in two groups: surgical services and medical
      services. Statistical software was used to calculate mean times between calls in
      specified time periods, and to compare differences between surgical and medical
      services. RESULTS: 25,389 pages were recorded. These data are presented as mean
      frequency of calls to each pager, divided into four time periods. The highest
      recorded rate was 6.9 minutes (mean) between calls in general surgery (1600-2200
      shift), with the lowest recorded rate a mean of one call per 5 hours (2200-0800
      shift) in geriatric and general medicine. CONCLUSIONS: Pager frequency is a
      potentially useful marker of job acuity and consequent junior doctor stress
      levels. This study demonstrated a high degree of variability in paging frequency
      both between services and between time periods. We recommend ongoing monitoring
      of paging frequencies and more even distribution of after-hours workload.

PMID- 16582975
TI  - Acting upstream to control the obesity epidemic in New Zealand.

PMID- 16582976
TI  - New Zealand's Christchurch Hospital at night: an audit of medical activity from
      2230 to 0800 hours.
AB  - OBJECTIVE: To audit medical activity at Christchurch Hospital New Zealand between
      2230 and 0800 hours; specifically, to measure the volumes of tasks requiring
      completion overnight and to identify the competencies required for this as well
      as the level of teamwork that existed. DESIGN: After a pilot study tested
      possible methods, Resident Medical Officers (RMOs) responsible for the care of
      adult patients at night were linked by a shift coordinator to recorders (mostly
      nursing students) trained to register the tasks performed, together with task
      urgency (as judged by the RMO) and duration. This information, checked each
      morning for completeness, was entered immediately into a database and analysed
      later. Telephonists logged all outbound calls through the hospital switchboard to
      on-call medical staff; theatre and admission records were recorded as usual.
      Anaesthetic and Radiology Registrar activity was self-recorded. SETTING:
      Christchurch Hospital is a 650 bed tertiary centre, which covers most
      specialties. MAIN OUTCOMES: In the absence of leadership, the RMOs were not
      working as a team. Consequently some were overextended while others were
      inactive. House officer tasks were largely generic--not specialty specific; there
      was no formal handover from the afternoon or day shifts and the level of hospital
      medical staffing did not reflect the activity levels over the time period
      studied. A review of the beep policy is urgently needed. A third of the
      admissions were to General Medicine, and basic medical activities (including
      admitting, reviewing, and prescribing drugs and fluids) for patients admitted
      under all specialties represented the majority of the night workload. Medical
      registrars had reduced some of the traditional multiple clerking by admitting
      patients themselves. The workload and its distribution over time was remarkably
      similar to that found at the 17 pilot sites in the United Kingdom, where Out of
      Hours Multidisciplinary Teams (OoHMT) were introduced. CONCLUSION: We recommend
      that Christchurch Hospital use these data to plan the composition and leadership
      of an OoHMT.

PMID- 16582977
TI  - Ethnicity data and primary care in New Zealand: lessons from the Health
      Utilisation Research Alliance (HURA) study.
AB  - AIMS: To explore issues in the collection and analysis of ethnicity data in
      primary care, and discuss the implications of this for health services research.
      METHODS: Data routinely collected by 25 Wellington Independent Practice
      Association (WIPA) general practices in 2001. RESULTS: Practices varied in the
      level of ethnicity data coverage achieved, ranging from less than 10% to greater
      than 90% of patients. Combining practice data with National Health Index (NHI)
      ethnicity data increased coverage to at least 70% for registered patients at 23
      of 25 practices. There were differences between the data collected in general
      practices and ethnicity recorded on NHI. However, with the exception of the
      'Other' category, this disagreement was not systematic. Practices had lower
      proportions of patients with ethnicity recorded as 'Other' (not further
      specified) than NHI ethnicity records. CONCLUSIONS: The study demonstrated that
      it is possible to collect quality ethnicity data in general practices, although
      there are challenges. Merging practice-collected ethnicity data with NHI
      ethnicity data increases coverage. However, there is some mismatch between data
      sources. The findings support the need for standardised, consistent approaches to
      ethnicity data collection and analysis, as well as systems and policies that
      facilitate the collection of high quality data.

PMID- 16582979
TI  - Tobacco industry fears of the World Conference of Tobacco or Health.

PMID- 16582978
TI  - Treating claudication in 5 words (stop smoking and keep walking) is no longer
      enough: an audit of risk factor management in patients prescribed exercise
      therapy in New Zealand.
AB  - AIM: To assess the documentation and modification of vascular risk factors in
      patients with intermittent claudication enrolled in an exercise programme in
      Christchurch, New Zealand. PATIENTS/METHOD: A retrospective review of case notes
      of patients who presented to the vascular outpatient department with intermittent
      claudication and were given "Green Prescriptions" for an exercise programme was
      performed. Referral letters, clinic letters, vascular nurse notes, and
      handwritten hospital notes were searched for evidence of documentation of risk
      factors for atherosclerosis. Modification of these risk factors was also noted.
      Positive attempts at risk factor modification included starting or asking the GP
      to start a medication or asking the GP to assist with smoking cessation. RESULTS:
      Sixty patient notes were reviewed which included 81 referral letters (66 from
      GPs), 118 surgeon letters/clinic notes, and 43 vascular nurse assessments. Of the
      60 patients referred, risk factor documentation (positive or negative) was
      antiplatelet therapy (40), hypertension (48), hyperlipidaemia (39), current
      tobacco use (40), diabetes mellitus (37), and coronary artery disease (38).
      Vascular surgeons saw 58 patients and documentation was antiplatelet therapy
      (42), hypertension (46), hyperlipidaemia (45), current tobacco use (48), diabetes
      mellitus (44), and coronary artery disease (29). Attempted modification of risk
      factors by vascular surgeons occurred in 12 patients for antiplatelet therapy, 11
      patients for lipid lowering therapy, and 10 for current smokers. Forty-three
      vascular nurse assessments resulted in documentation of antiplatelet therapy (0),
      hypertension (42), hyperlipidaemia (42), current tobacco use (43), diabetes
      mellitus (42), and coronary artery disease (6). CONCLUSION: There is suboptimal
      communication of vascular risk factors by referrers to specialist vascular
      services. The recording and modification of risk factors for atherosclerosis in
      our unit compares favourably with other reported series, but improvement is
      needed. Furthermore, the role of clinicians with an interest in risk factor
      management, and patients' understanding of their vascular risk factors, needs
      clarification.

PMID- 16582980
TI  - Leadership at night in New Zealand hospitals.

PMID- 16582981
TI  - PHARMAC and treatment of bipolar depression--the limits of utilitarianism.
AB  - Bipolar disorder affects 1.6% of the population. The majority of the burden of
      illness for people with bipolar disorder is due to depression. Suicide rates for
      people with bipolar disorder are 15 times higher than in the general population,
      and the majority of these deaths occur during depressive episodes. More effective
      prevention of such depressive episodes is important. Lamotrigine is an
      anticonvulsant and a mood stabiliser that is more effective at preventing
      depressive relapses than most other mood stabilising drugs. Its use for this
      purpose has been recommended by English language treatment guidelines since 2002.
      Lamotrigine is approved for use in the prophylaxis of depression in bipolar
      disorder and for epilepsy. PHARMAC subsidises its use in treatment-resistant
      epilepsy (subject to a 'special authority' application) but not in bipolar
      disorder. The New Zealand Mental Health Strategy and the imminent New Zealand
      Suicide Strategy identify reducing suicide as a key goal. Among other
      initiatives, this requires effective treatment of bipolar depression, yet a
      treatment likely to support this is not currently subsidised.

PMID- 16582982
TI  - Establishing Mobility Measures to Assess the Effectiveness of Night Vision
      Devices: Results of a Pilot Study.
AB  - In preparation for an evaluation of night vision devices, an exploratory study
      was conducted to gain initial experience with the sensitivity of chosen mobility
      measures under night conditions. The measures included cane contacts and object
      recognition distances. Results provide preliminary evidence that these two
      measures may be sensitive to the effects of a night vision device.

PMID- 16582983
TI  - Electro-Chemical Modeling Challenges of Biological Ion Pumps.
AB  - We outline the basic operational, structural and functional features of ion
      motive ATPases: transmembrane proteins central to biological functions of all
      animal cells. As an example we discuss the modeling problems associated with the
      operation of the surface membrane Na(+),K(+)-ATPase and skeletal muscle
      sarcoplasmic reticulum Ca(2+)-ATPase and focus on the frameworks required for
      their solution. There are three basic problems: identification of the pathway for
      ion permeation, prediction of ion binding rate coefficients and affinities based
      on the structure of the protein, and prediction of conformational changes of
      protein structure and the associated movement of charges within the membrane
      dielectric. A solution strategy useful in approaching the first two problems and
      preliminary results obtained using molecular dynamics simulations are also
      presented.

PMID- 16582984
TI  - Evaluation of DNA damage in white blood cells of healthy human volunteers using
      the alkaline comet assay and the chromosome aberration test.
AB  - The present study was undertaken to contribute to the characterization of the
      degree of variability in baseline damage in white blood cells from control
      population, and to investigate how this variability is associated with external
      and internal factors. Altogether 170 healthy volunteers, randomly selected from
      the general population of the Republic of Croatia, participated in the study. Two
      sensitive tests: the alkaline comet assay and the chromosome aberration test were
      applied to study the background levels of DNA damage in their white blood cells.
      The results point to inter-individual differences, indicating different genome
      sensitivity. As revealed by both assays, the background levels of DNA damage were
      mostly influenced by smoking habit as well as medical exposure (especially to
      diagnostic X-rays). Sex and age of subjects did not significantly influence the
      values of DNA damage recorded in the white blood cells. Although higher levels of
      DNA damage were recorded in blood samples collected during winter and autumn,
      they were mostly influenced by medicinal exposure and smoking habit. Statistical
      evaluation of the data confirmed that a positive correlation exists between DNA
      migration and the number of long-tailed nuclei found with the comet assay and the
      total number of chromosome aberrations. The data obtained can serve as control
      values in forthcoming biomonitoring studies.

PMID- 16582985
TI  - Mammalian DNA methyltransferases.
AB  - DNA methylation is an epigenetic process affecting gene expression and chromatin
      organization. It can heritably silence or activate transcription of genes without
      any change in their nucleotide sequences, and for a long time was not recognized
      as an important regulatory mechanism. However, during the recent years it has
      been shown that improper methylation, especially hypermethylation of promoter
      regions, is observed in nearly all steps of tumorigenesis. Aberrant methylation
      is also the cause of several major pathologies including developmental disorders
      involving chromosome instabilities and mental retardation. A great progress has
      been made in our understanding of the enzymatic machinery involved in
      establishing and maintaining methylation patterns. This allowed for the
      development of new diagnostic tools and epigenetic treatment therapies. The new
      approaches hold a great potential; several inhibitors of DNA methyltransferases
      have already shown very promising therapeutic effects.

PMID- 16582986
TI  - Optimization of transient Agrobacterium-mediated gene expression system in leaves
      of Nicotiana benthamiana.
AB  - Here we report on a simple and reproducible system of Agrobacterium-mediated
      transient gene expression assay that utilizes infiltration of young Nicotiana
      benthamiana leaves. Although some of the phenomena described in this paper have
      been already reported by other researchers, here we have further developed them.
      The highest level of transient gfp gene expression was detected in the youngest
      leaves of N. benthamiana infiltrated with A. tumefaciens strains AGL0 and EHA105
      precultured in the presence of 450-600 microM acetosyringone. Although the
      maximum level of transient gfp gene expression was restricted presumably by RNA
      silencing, it was completely suppressed in the presence of the viral protein HC
      Pro. The transient expression system described here can be used to identify new
      viral suppressors of RNA silencing, for detailed analysis of unidentified genes
      and for industrial production of proteins in plants as well.

PMID- 16582987
TI  - Sequence-specific p53 gene damage by chloroacetaldehyde and its repair kinetics
      in Escherichia coli.
AB  - Oxidative stress and certain environmental carcinogens, e.g. vinyl chloride and
      its metabolite chloroacetaldehyde (CAA), introduce promutagenic exocyclic adducts
      into DNA, among them 1,N(6)-ethenoadenine (epsilonA), 3,N(4)-ethenocytosine
      (epsilonC) and N(2),3-ethenoguanine (epsilonG). We studied sequence-specific
      interaction of the vinyl-chloride metabolite CAA with human p53 gene exons 5-8,
      using DNA Polymerase Fingerprint Analysis (DPFA), and identified sites of the
      highest sensitivity. CAA-induced DNA damage was more extensive in p53 regions
      which revealed secondary structure perturbations, and were localized in regions
      of mutation hot-spots. These perturbations inhibited DNA synthesis on undamaged
      template. We also studied the repair kinetics of CAA-induced DNA lesions in E.
      coli at nucleotide resolution level. A plasmid bearing full length cDNA of human
      p53 gene was modified in vitro with 360 mM CAA and transformed into E. coli
      DH5alpha strain, in which the adaptive response system had been induced by MMS
      treatment before the cells were made competent. Following transformation,
      plasmids were re-isolated from transformed cultures 35, 40, 50 min and 1-24 h
      after transformation, and further subjected to LM-PCR, using ANPG, MUG and Fpg
      glycosylases to identify the sites of DNA damage. In adaptive response-induced E.
      coli cells the majority of DNA lesions recognized by ANPG glycosylase were
      removed from plasmid DNA within 35 min, while MUG glycosylase excised base
      modifications only within 50 min, both in a sequence-dependent manner. In non
      adapted cells resolution of plasmid topological forms was perturbed, suggesting
      inhibition of one or more bacterial topoisomerases by unrepaired epsilon-adducts.
      We also observed delayed consequences of DNA modification with CAA, manifesting
      as secondary DNA breaks, which appeared 3 h after transformation of damaged DNA
      into E. coli, and were repaired after 24 h.

PMID- 16582988
TI  - Calixarene-encapsulated nanoparticles: self-assembly into functional
      nanomaterials.
AB  - Calixarenes are excellent surfactants for enhancing the dispersion and self
      assembly of metal nanoparticles into well-defined structures, particularly those
      with unit length scales in the 10-100 nm size range. Particles within these
      ensembles are strongly coupled, giving rise to unique collective optical or
      magnetic properties. The self-assembled nanostructures described in this feature
      article include 2D arrays of colloidal Au nanoparticles with size-dependent
      plasmonic responses, and sub-100 nm Co nanoparticle rings with chiral magnetic
      states. These nanoparticle assemblies may be further developed for applications
      in chemical sensing based on surface-enhanced Raman scattering (SERS) and as
      binary elements for nonvolatile memory, respectively.

PMID- 16582989
TI  - New ambient pressure organic superconductors kappa H- and kappa L-(DMEDO
      TSeF)2[Au(CN)4](THF).
AB  - We have developed two novel organic superconductors kappa H- and kappa L-(DMEDO
      TSeF)2[Au(CN)4](THF) (DMEDO-TSeF = dimethyl(ethylenedioxy)tetraselenafulvalene)
      with the onset transition temperatures of 4.8 K for the kappa H-phase and 3.0 K
      for the kappa L-phase at ambient pressure, where DMEDO-TSeF is the second example
      following tetramethyltetraselenafulvalene (TMTSF) after an interval of 25 years
      as a sulfur-free donor providing a bulk organic superconductor.

PMID- 16582990
TI  - Selective recognition of bacterial membranes by zinc(II)-coordination complexes.
AB  - Two fluorophore-dipicolylamine-Zn2+ conjugates are shown by epifluorescence
      microscopy to stain the membranes of bacterial cells in preference to mammalian
      cells.

PMID- 16582991
TI  - A mechanical "flip-switch". Interconversion between co-conformations of a
      [2]rotaxane with a single recognition site.
AB  - [2]Rotaxanes utilising the 1,2-bis(pyridinium)ethane, 24-crown-8 motif can exist
      in two distinct co-conformations whose relative abundances are solvent dependent.

PMID- 16582992
TI  - Diplatinum alkynyl chromophores as sensitisers for lanthanide luminescence in
      Pt2Ln2 and Pt2Ln4 (Ln = Eu, Nd, Yb) arrays with acetylide-functionalized
      bipyridine/phenanthroline.
AB  - Incorporation of diplatinum complex Pt2(micro-dppm)2(bpyC[triple bond]C)4 or
      Pt2(mu-dppm)2(phenC[triple bond]C)4 with Ln(hfac)3(H2O)2 (Ln = Nd, Eu, Yb) gave a
      series of Pt2Ln2 and Pt2Ln4 bimetallic arrays, in which the excitation of d(Pt) -
      >pi*(R-C[triple bond]C) MLCT absorption induces sensitisation of lanthanide
      luminescence through efficient d --> f energy transfer from Pt(II) alkynyl
      chromophores.

PMID- 16582993
TI  - Conformational locking for band gap control in 3,4-propylenedioxythiophene based
      electrochromic polymers.
AB  - We report a tethered poly(3,4-propylenedioxythiophene) derivative with a built-in
      polymer conformation restriction which locks the conjugated chain at a specific
      dihedral angle, thus providing a handle in which to tune the optical and
      electronic properties of the material.

PMID- 16582994
TI  - A new Co(II) coordination solid with mixed oxygen, carboxylate, pyridine and
      thiolate donors exhibiting canted antiferromagnetism with T(C) approximately 68
      K.
AB  - Reaction of Co(II) chloride with the sodium salt of 2-mercaptonicotinic acid in
      water at 200 degrees C results in the formation of Co4(2-mna)4(H2O), which orders
      as a canted antiferromagnet at 68 K.

PMID- 16582995
TI  - Polymerized surface micelles formed under mild conditions.
AB  - A new polymerizable surfactant 1-[11-(lipoyloxy)-undecyl]-pyridinium bromide was
      synthesized, which provides a new approach for polymerizing micelles under mild
      conditions.

PMID- 16582996
TI  - Complexes of iron and cobalt with new tripodal amido-polyphosphine hybrid
      ligands.
AB  - Divalent complexes of iron and cobalt with new, monoanionic tripodal amido
      polyphosphine ligands have been thoroughly characterized, and XRD analysis
      reveals geometries that are distinct for this class of ligand.

PMID- 16582997
TI  - Perforated organometallic nanotubes prepared from a Rh N-heterocyclic carbene
      using a porous alumina membrane.
AB  - Fabrication of perforated organometallic nanotubes using a di-rhodium bis(N
      heterocyclic carbene) complex by a simple nanoporous template wetting technique
      is described along with characterization data from scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), energy dispersive X-ray
      spectroscopy (EDS), proton NMR and Mass spectroscopy.

PMID- 16582998
TI  - Demonstration of a magnetic and catalytic Co@Pt nanoparticle as a dual-function
      nanoplatform.
AB  - Co@Pt nanoparticles as a bifunctional nanoplatform system for the hydrogenation
      of various unsaturated organic molecules under mild conditions and also for
      magnetic separation and recycling are demonstrated.

PMID- 16582999
TI  - Synthesis and characterization of monodisperse silica-polyaniline core-shell
      nanoparticles.
AB  - Monodisperse silica-polyaniline core-shell nanoparticles with an average diameter
      of 26 nm were synthesized by in-situ polymerisation of aniline monomers adsorbed
      on the silica surface through electrostatic interactions.

PMID- 16583000
TI  - Crystallographic observation of an olefin photodimerization reaction that takes
      place via thermal molecular tumbling within a self-assembled host.
AB  - In situ crystallography reveals that the solid state [2 + 2] photodimerization of
      acenaphthylene in a coordination cage takes place smoothly without
      preorganizaiton of reaction centers at a preferred geometry, because the
      substrate tumbles thermally in the large hollow of the cage.

PMID- 16583001
TI  - A new chalcogenide homologous series A2[M(5+n)Se(9+n)] (A = Rb, Cs; M = Bi, Ag,
      Cd).
AB  - The ternary and quaternary selenides, beta-CsBi3Se5, Rb2CdBi6Se11,
      CsAg(0.5)Bi(3.5)Se6, CsCdBi3Se6, Rb2Ag(1.5)Bi(7.5)Se13, and
      Cs2Ag(1.5)Bi(7.5)Se13, are all members of the new homologous series
      A2[M(5+n)Se(9+n)] and crystallize in structures related to each other in a
      systematic way; these compounds are mid gap semiconductors and are of interest as
      thermoelectric materials.

PMID- 16583002
TI  - Electrochemical oxidation of catechol in the presence of cyclopentadiene.
      Investigation of electrochemically induced Diels-Alder reactions.
AB  - We describe the synthesis and kinetic evaluation of compounds from [4 + 2] alone
      and [4 + 2] followed by [2 + 2] cycloaddition reactions of electrochemically
      generated o-benzoquinone with 1,3-cyclopentadiene.

PMID- 16583003
TI  - The cyclic [N(PiPr2E)2]+ (E = Se, Te) cations: a new class of inorganic ring
      system.
AB  - The two-electron oxidation of [(tmeda)NaN(PiPr2E)2] with iodine produces the
      cyclic [N(PiPr2E)2]+ (E = Se, Te) cations, which exhibit long E-E bonds in the
      iodide salts.

PMID- 16583004
TI  - Thiolated PAMAM dendrimer-coated CdSe/ZnSe nanoparticles as protein transfection
      agents.
AB  - Functionalisation of PAMAM dendrimers with a small number of thiol groups makes
      them good ligands for CdSe/ZnSe nanoparticles; the particles coated with
      thiolated dendrimers have good cell permeability and are potent transfection
      agents.

PMID- 16583005
TI  - Organic rectifying junctions from an electron-accepting molecular wire and an
      electron-donating phthalocyanine.
AB  - Self-assembled monolayers (SAMs) of arylene-ethynylene oligomers that incorporate
      electron-accepting 9-fluorenone and 9-[(4-pyridyl)methylene]fluorene units in the
      backbone exhibit symmetrical current-voltage (I-V) characteristics, but
      rectifying junctions with current ratios of 20-80 at +/-1 V have been obtained by
      protonating these wire-like molecules and ionically coupling with anionic donors.

PMID- 16583006
TI  - On the origin of the Murchison meteorite phosphonates. Implications for pre
      biotic chemistry.
AB  - Ab initio calculations, combined with experimental studies on the anaerobic
      hydrolysis of phosphaalkynes under thermal and photochemical conditions suggest a
      potential, exogenous source of reduced oxidation state phosphorus for the early
      Earth.

PMID- 16583007
TI  - Synthesis and reactivity of a 9-membered azaenediyne: importance of proximity
      effect in N-alkylation.
AB  - Synthesis of a 9-membered azaenediyne has been achieved for the first time via
      intramolecular N-alkylation; the importance of proximity of the reacting centres
      via cobalt carbonyl complexation of the acetylenic moiety and not the activation
      of propargylic carbon has been demonstrated.

PMID- 16583008
TI  - Surface-assisted one-dimensional self-assembly of a perylene based semiconductor
      molecule.
AB  - Chloroform-vapor annealing of thin films of propoxyethyl perylene tetracarboxylic
      diimide (PE-PTCDI, an n-type semiconductor) deposited on glass or mica leads to
      formation of well-defined one-dimensional self-assemblies (e.g. nanobelts), which
      show optically uniaxial properties as demonstrated by the linearly polarized
      emission.

PMID- 16583010
TI  - Controlled one-step fabrication of highly oriented ZnO nanoneedle/nanorods arrays
      at near room temperature.
AB  - Highly oriented ZnO nanoneedle/nanorods arrays have been fabricated by direct
      oxidation of zinc foil in alkaline zincate ion solution at near room temperature
      (20 degrees C for nanoneedles, 30 degrees C for nanorods).

PMID- 16583009
TI  - An iterative route to "decorated" ethylene glycol-based linkers.
AB  - Iterative copper-catalyzed cycloadditions of azides to alkynes were used to join
      functionalized triethylene glycol molecules to give "linkers" of defined lengths
      equipped with several different end-group functionalities.

PMID- 16583011
TI  - Porphyrin cored hyperbranched polymers as heme protein models.
AB  - The single step synthesis of an Fe(II) porphyrin cored hyperbranched polymer,
      possessing similar size and topology to the natural heme containing proteins, is
      reported: UV spectroscopy successfully demonstrated the ability of this polymer
      to reversibly bind oxygen.

PMID- 16583012
TI  - Self-assembled microspheres from f-block elements and nucleoamphiphiles.
AB  - Hollow microspheres featuring a hybrid lipid-cation multilamellar shell are
      prepared by hydration of a nucleoside based amphiphile with an aqueous solution
      containing either actinide or lanthanide salts. The physico-chemical data
      collected clearly indicate that the formation of these microspheres is a
      consequence of the following concomitant stabilizing factors: (i) hydrophobic
      interactions, (ii) nucleobase dimer formation and (iii) phosphate/f-block element
      salt binding.

PMID- 16583013
TI  - Synergistic hybrid catalyst for cyclic carbonate synthesis: remarkable
      acceleration caused by immobilization of homogeneous catalyst on silica.
AB  - The catalytic activity of phosphonium salts towards cyclic carbonate synthesis
      from propylene oxide and CO2 has been enormously enhanced by their immobilization
      onto silica that itself has no catalytic activity.

PMID- 16583014
TI  - Strategy for the synthesis of multivalent peptide-based nonsymmetric dendrimers
      by native chemical ligation.
AB  - A strategy for the synthesis of multivalent peptide-based nonsymmetric dendrimers
      by native chemical ligation using poly(lysine) dendritic wedges as scaffolds is
      presented.

PMID- 16583015
TI  - Coating carbon nanotubes with polymer in supercritical carbon dioxide.
AB  - A facile and efficient method has been developed for coating MWNTs with solvent
      resistant polymer in scCO2, which permits the selective deposition of high
      molecular weight fluorinated graft poly(methyl vinyl ether-alt-maleic anhydride)
      polymer onto MWNTs in scCO2 under 100-170 bar at 40 degrees C and forms quasi one
      dimensional nanostructures with conducting cores and insulating surfaces.

PMID- 16583016
TI  - Solvent dependent photocyclization and photophysics of some 2-ethynylbiphenyls.
AB  - The spectroscopic properties and photochemical behavior of molecules having 2
      ethynylbiphenyl or 2-phenyldiphenylacetylene structures are reported. These
      molecules undergo photocyclization reactions to yield phenanthrene and
      dihydrophenanthrene products via putative isophenanthrene (cyclic allene)
      intermediates. Phenanthrene formation from the isophenanthrene intermediates does
      not occur via a unimolecular sigmatropic hydrogen shift, but rather by
      protonation or hydrogen abstraction mechanisms involving the solvent. Cyclization
      efficiencies are much lower than is the case for previously-investigated 2
      vinylbiphenyl systems. The 2-phenyldiphenylacetylenes have high fluorescence
      quantum yields and long singlet lifetimes when compared to diphenylacetylene. The
      2-ethynylbiphenyls decay via a combination of fluorescence and intersystem
      crossing.

PMID- 16583017
TI  - Photochemical production and characterisation of the radical ions of
      tetraphenylporphycenes.
AB  - Both the radical anion and radical cation of 2,7,12,17-tetraphenylporphycene and
      of its palladium(II) complex have been produced by photochemical methods. Their
      electronic absorption spectrum and decay kinetics have been characterised by
      global analysis of the time-absorbance-wavelength matrix. The results provide
      deeper insight on the role of these radical ion species in the photodynamic
      activity of tetraphenylporphycenes.

PMID- 16583018
TI  - Spectroscopic study of TPPS4 nanostructures in the presence of bovine serum
      albumin.
AB  - The influence of bovine serum albumin (BSA) on the formation of J-aggregates of
      meso-tetra(4-sulfonatophenyl)porphine (TPPS4) in aqueous acid solution (pH 1.3)
      has been investigated by means of absorption and fluorescence spectroscopy. TPPS4
      concentration was kept constant at 2 microM while BSA concentration was varied to
      get TPPS4 : BSA molar ratios from 1 : 0.005 to 1 : 20. In the presence of protein
      at all used concentrations the intensity of J-aggregates absorption band was
      higher than that in the pure solution. Spectral changes indicated that the
      dynamic equilibrium of the aggregated TPPS4 species was highly dependent on the
      molar ratio between TPPS4 and BSA. Small relative concentrations of BSA (TPPS4 :
      BSA, 1 : 0.005-1 : 0.1) had a stimulating effect on formation of J-aggregates.
      Several fractions of J-aggregates located in protein and aqueous moieties were
      detected in mixed solutions at intermediate BSA concentrations (TPPS4 : BSA, 1 :
      0.5-1 : 8), when the absorbance intensity of the J-aggregates was the highest. At
      the highest used BSA concentrations (TPPS4 : BSA, 1 : 10-1 : 20) the spectral
      properties of the remaining J-aggregates were similar to those typical for pure
      porphyrin solution. Additionally, the split of the Soret band into two with peaks
      at 440 nm and 423 nm was followed by the simultaneous appearance of Q bands and
      reflected the formation of TPPS4-BSA complexes including both protonated and
      deprotonated TPPS4 forms.

PMID- 16583019
TI  - Retardation of interfacial charge recombination by addition of quaternary
      ammonium cation and its application to low temperature processed dye-sensitized
      solar cells.
AB  - Electron lifetime (tau) in dye-sensitized solar cells (DSC), using electrolytes
      containing I-/I3- redox couple, was investigated with quaternary ammonium cations
      having various alkyl chain lengths, and it was found that the lifetime increased
      in the order tau(TPA) approximately tau(TBA) < tau(THA) approximately tau(THpA),
      where tau(TPA), tau(TBA), tau(THA) and tau(THpA) were the lifetimes with tetra
      propyl, butyl, hexyl and heptyl ammonium cations respectively. On the other hand,
      little influence of the cations on electron diffusion coefficients was observed,
      indicating that the DSCs using these cations have longer electron diffusion
      length (L). New electrolyte compositions for DSCs were sought with THA+ to
      increase the lifetime and L without compromising charge injection yield from the
      dye to TiO2. The electrolyte was applied for DSCs using TiO2 electrode prepared
      by 150 degrees C sintering. Under one-sun conditions (100 mW cm(-2)), newly
      prepared electrolytes showed at most 40% increase of energy conversion efficiency
      in comparison to conventional electrolytes and the highest value was 4.7%, which
      was the highest among the reported values of low temperature processed DSCs. The
      increase of the efficiency was achieved by higher short-circuit current induced
      by longer electron diffusion length and higher open-circuit voltage due to higher
      electron density.

PMID- 16583020
TI  - Impact of iron-complex (Fe(III)-NTA) on photoinduced degradation of 4
      chlorophenol in aqueous solution.
AB  - In this research work, the photochemical impact of Fe(III)-nitrilotriacetic acid
      complex (FeNTA) on the fate of an organic pollutant (4-chlorophenol (4-CP)) was
      investigated in natural waters. The quantum yields of the photodecomposition of
      the FeNTA complex and of Fe(II) formation, by an intra-molecular photoredox
      process (the first stage of the reaction) are high. This photoredox reaction
      represents the first step of the process leading to 4-CP disappearance. Whereas
      oxygen does not affect FeNTA photodegradation, 4-CP depletion requires the
      presence of oxygen. The radical species HO and CO3*- responsible of the
      degradation were identified by ESR spectroscopy under irradiation. Two different
      wavelength-dependent mechanisms of 4-chlorophenol degradation are proposed. It
      clearly appears that under solar irradiation, iron organic complexes like FeNTA
      can play a significant role on the fate of the organic compounds present in
      natural waters.

PMID- 16583021
TI  - Temperature dependence of collagen fluorescence.
AB  - Dermal collagens have several fluorescent moieties in the UV and visible spectral
      regions that may serve as molecular probes of collagen. We studied the
      temperature-dependence of a commercial calf skin collagen and acid-extracted Skh
      1 hairless mouse collagen at temperatures from 9 degrees C to 60 degrees C for
      excitation/emission wavelengths 270/305 nm (tyrosine), 270/360 nm (excimer-like
      aggregated species), 325/400 nm (dityrosine) and 370/450 nm (glycation adduct). L
      tyrosine (1 x 10(-5) M in 0.5 M HOAc) acted as a "reference compound" devoid of
      any collagen structural effects. In general, the fluorescence efficiency of these
      fluorophores decreases with increasing temperature. Assuming that rate constant
      for fluorescence deactivation has the form k(d)(T) = k(d) degrees exp (
      DeltaE/RT), an Arrhenius plot of log[(1/Phi) - 1] vs. 1/T affords a straight line
      whose (negative) slope is proportional to the activation energy, DeltaE, of the
      radiationless process(es) that compete with fluorescence. Because it is difficult
      to accurately measure Phi(f) for collagen-bound fluorophores, we derived an
      approximate formula for an activation parameter, DeltaE*, evaluated from an
      Arrhenius-like plot of log 1/I(N)vs. 1/T, (1/I(N)vs. is the reciprocal normalized
      fluorescence intensity). Tyrosine in dilute solution affords a linear Arrhenius
      plot in both of the above cases. Using the known value of Phi(f) = 0.21 for free
      tyrosine at room temperature, we determined that DeltaE* is accurate to
      approximately 25% in the present instance. Collagen curves are non-linear, but
      they are quasi-linear below approximately 20 degrees C, where the helical form
      predominates. Values of DeltaE* determined from the data at T < 20 degrees C
      ranged from 6.2-8.4 kJ mol(-1) (1.5-2.0 kcal mol(-1)) for mouse collagen and 10.3
      11.4 kJ mol(-1) (2.5-2.7 kcal mol(-1)) for calf skin collagen, consistent with
      collisional deactivation of the fluorescent state via thermally enhanced
      molecular vibrations and rotations. Above 20 degrees C, log 1/I(N)vs. 1/T plots
      from Skh-1 hairless mouse collagen are concave-downward, suggesting that
      fluorescence deactivation from the denatured coil has a significant temperature
      independent component. For calf skin collagen, these plots are concave-upward,
      suggesting an increase in activation energy above Tm. These results suggest that
      collagen backbone and supramolecular structure can influence the temperature
      dependence of the bound fluorophores, indicating the future possibility of using
      activation data as a probe of supramolecular structure and conformation.

PMID- 16583022
TI  - Photochemically enhanced adenoviral transduction in a multicellular environment.
AB  - Photochemical internalization (PCI) enhances adenovirus (Ad) transgene expression
      in a variety of cell lines in vitro. However, measurements of the photochemical
      effect on transduction in multicellular environments are lacking. In this study,
      spheroids of DU 145 prostate cancer cells were used as a model to evaluate Ad
      serotype 5 (Ad5) transduction in a multicellular environment in response to PCI
      treatment. Furthermore, the Ad5 was coated with poly(2-methyl-acrylic acid 2-[(2
      (dimethylamino)-ethyl)-methyl-amino]-ethyl ester) (pDAMA) to evaluate whether
      physicochemical properties such as charge and size of viral vectors affect
      transduction of photochemically treated spheroids. Spheroids incubated with
      photosensitizer TPPS(2a) (1 microg ml(-1)) and infected with adenovirus contained
      3-fold higher percentage of reporter gene expressing cells after exposure to blue
      light (0.42 J cm(-2)) compared to no light, as analysed by flow cytometry of
      dissociated spheroids two days after treatment. The cells within the infected
      spheroids were further divided into three sections corresponding to the interior,
      intermediate and peripheral layers of the spheroids. This was performed by
      staining the spheroids with a diffusion-limited dye prior to dissociation.
      Transduction of cells within photochemically treated and untreated spheroids was
      heterogeneous, with a radial reduction of transgene expression towards the inner
      section of the spheroid. The coating of Ad with pDAMA induced up to 2-fold
      decrease in transduction of cells in the interior section of spheroids compared
      to uncomplexed Ad, while transduction of the peripheral section remained
      unchanged. The decrease in transduction could be related to reduced diffusion due
      to the size of the Ad-pDAMA complexes.

PMID- 16583023
TI  - Reaction mechanisms of riboflavin triplet state with nucleic acid bases.
AB  - ESR and laser flash photolysis studies have determined a reasonable order of
      reactivity of nucleotides with triplet riboflavin (3Rb*) for the first time. ESR
      detection of triplet state reactivity of Rb with nucleoside, polynucleotide and
      DNA has been obtained simultaneously. In addition, ESR spin elimination
      measurement of the reactivity of 3Rb* with nucleotides in good accord with laser
      flash photolysis determination of the corresponding rate constants offers a
      simple and reliable method to detect the reactivities of nucleic acids and its
      components with photoexcited flavins. Kinetic, ESR and thermodynamic studies have
      demonstrated that Rb should be a strong endogenous photosensitizer capable of
      oxidizing all nucleic acid bases, and preferentially two purine nucleotides with
      high rate constants.

PMID- 16583024
TI  - Flash-photolytic generation of dienols and dienolates from alpha,beta-unsaturated
      esters and kinetics of their amine-catalyzed ketonization in nonaqueous media.
AB  - Dienols of alpha,beta-unsaturated esters were generated and observed by flash
      photolysis and their decay rates in acetonitrile and in hexane solutions were
      measured in the presence of amines or aminoalcohols. In acetonitrile, 1 ratio 1
      ammonium dienolate transient intermediates were observed. In hexane, no dienolate
      could be detected and two moles of the inductor participated in the rate
      determining step for tautomerization.

PMID- 16583025
TI  - Porphyra-334, a potential natural source for UVA protective sunscreens.
AB  - The mycosporine-like amino acid (MAA), porphyra-334 (lambda(max) = 334 nm;
      epsilon = 42,300 M(-1) cm(-1)), was isolated from the aquatic cyanobacterium
      Aphanizomenon flos-aquae (AFA) and its structure was verified by spectroscopic
      methods. The UVA absorption properties of the crude methanolic extract were
      determined against two commercial sun care products in terms of mean critical
      wavelength, mean UVA/UVB ratios and UVA protection category (Boots the Chemists,
      Ltd.). The crude methanolic extract from AFA exhibited maximum UVA protection
      comparable to that determined for Boots SPF 4.

PMID- 16583026
TI  - [A study on the epidemiologic cynetics of the human infection by Trypanosoma
      cruzi through the application of the "reversible catalytic model". Rev Saude
      Publ. 3(1):23-29, June 1969].

PMID- 16583027
TI  - [Guilherme Rodrigues da Silva, rhythms and flavors from Bahia in Brazilian
      epidemiology].

PMID- 16583028
TI  - The reversible catalytic model and the mathematical theory of epidemics.

PMID- 16583029
TI  - [Epidemiometric models in tuberculosis: definition of "states" and risk of
      infection. Rev Saude Publ. 11:188-98, 1977].

PMID- 16583030
TI  - [Origins of research on the dynamics of tuberculosis' transmission in Brazil].

PMID- 16583031
TI  - Barriers for HIV testing during pregnancy in Southern Brazil.
AB  - OBJECTIVE: To assess HIV testing rate and determine risk factors for not have
      been tested during pregnancy. METHODS: A cross-sectional study was carried out in
      Porto Alegre, Southern Brazil, from December 2000 to February 2001.
      Socioeconomic, maternal and healthcare variables were obtained by means of a
      standardized questionnaire. Crude and adjusted odds ratios and their 95%
      confidence intervals were obtained in logistic regression models. RESULTS: A
      total of 1,642 mothers were interviewed. Of them, 94.3% reported being offered
      HIV testing before or during pregnancy or during labor; 89 mothers (5.4%) were
      not tested or did not know if they were tested. Attending fewer than six prenatal
      visits, being single and younger than 18 years old were relevant barriers
      preventing HIV testing. There was found a relationship between maternal schooling
      and the category of prenatal care provider. Having low 22.20 (12.43-39.67) or
      high 3.38 (1.86-7.68). schooling and being cared in the private sector strongly
      reduced the likelihood of being HIV tested. CONCLUSIONS: The Brazilian Health
      Ministry's recommendation for universal counseling and HIV testing has been
      successfully implemented in the public sector. In order to improve HIV testing
      coverage, new strategies need to target women cared in the private sector
      especially those of low schooling.

PMID- 16583032
TI  - [Factors associated with preference for cesarean delivery].
AB  - OBJECTIVE: To study factors related to preference for cesarean delivery, among
      pregnant women without medical complications. METHODS: A cross-sectional study
      was carried out among 156 pregnant women, in a private clinic in the city of
      Osasco, State of Sao Paulo, from October 2000 to December 2001. The pregnant
      women were at 28 weeks of pregnancy or more, with no formal contraindication for
      vaginal delivery at the time of the interview. Sociodemographic data and past and
      present obstetric history were assessed by applying a questionnaire. The pregnant
      women were specifically asked what their current preference for delivery was.
      Pearson's Chi-square test and logistic regression for multivariate analysis were
      performed with a 5% significance level. RESULTS: Sixty-seven pregnant women
      (42.9%) said they had little motivation to undergo vaginal delivery. In the
      multivariate analysis, the following variables were statistically significant:
      previous vaginal birth (p=0.001; ORadj=0.04; 95% CI=0.01-0.12); husband's monthly
      income greater than 750 reais (p=0.006, ORadj=3.44; 95% CI=1.38-8.33). The women
      with a previous vaginal delivery presented 25-fold lower chance of choosing
      cesarean delivery. The opinion that the previous delivery experience was
      unsatisfactory was marginally associated with the main outcome (p=0.06;
      ORadj=0.42; 95% CI=0.16-1.05). CONCLUSIONS: Motivation for cesarean delivery is
      associated with influences such as the type and degree of satisfaction with
      previous delivery and income.

PMID- 16583033
TI  - Brazilian doctors' perspective on the second opinion strategy before a C-section.
AB  - OBJECTIVE: To describe the opinion of doctors who participated in the Latin
      American Study on Cesarean section in Brazil regarding the second opinion
      strategy when faced with the decision of performing a C-section. METHODS: Seventy
      two doctors from the hospitals where the study took place (where the second
      opinion was routinely sought) and 70 from the control group answered a pre-tested
      self-administered structured questionnaire. Descriptive tables were prepared
      based on the frequency of relevant variables on opinion of physicians regarding:
      effectiveness of the application of the second opinion strategy; on whether they
      would recommend implementation of this strategy and reasons for not recommending
      it in private institutions; feasibility of the strategy implementation and
      reasons for not considering this implementation feasible in private institutions.
      RESULTS: Half of the doctors from the intervention hospitals (50%) and about two
      thirds of those in the control group (65%) evaluated the second opinion as being
      or having the potential of being effective/very effective in their institutions.
      The great majority of those interviewed from both intervention and control
      hospitals considered this strategy feasible in public (87% and 95% respectively)
      but not in private hospitals (64% and 70% respectively), mainly because in the
      latter the doctors would not accept interference from a colleague in their
      decision-making process. CONCLUSION: Although the second opinion strategy was
      perceived as effective in reducing C-section rates, doctors did not regard it
      feasible outside the public health system in Brazil.

PMID- 16583035
TI  - [Translation and content validation of the Childhood Trauma Questionnaire into
      Portuguese language].
AB  - OBJECTIVE: The Childhood Trauma Questionnaire is a self-applied instrument for
      adolescents and adults to assess childhood abuse. The objective was to translate,
      adapt and validate the questionnaire content into a Portuguese language version
      called Questionario sobre Traumas na Infancia. METHODS: The translation and
      adaptation into Portuguese was carried out in five steps: (1) translation; (2)
      back translation; (3) correction and semantic adaptation; (4) content validation
      by professional experts (judges); and (5) a final critical assessment by the
      target population using a verbal rating scale. RESULTS: The translated and
      adapted 28-item Portuguese version of the scale and instructions produced an
      instrument called Questionario sobre Traumas na Infancia. In the assessment by
      the target population, 32 adult users of the Brazilian Unified Health System
      answered the questionnaire and showed good understanding of the instrument
      (mean=4.86 +/- 0.27) in the verbal rating scale. CONCLUSION: The questionnaire's
      Portuguese version proved to be easily understandable showing good semantic
      validation. Nevertheless, further studies should address other psychometric
      characteristics of this instrument.

PMID- 16583034
TI  - Case-control study on infant mortality in Southern Brazil.
AB  - OBJECTIVE: To identify risk factors associated with infant mortality and, more
      specifically, with neonatal mortality. METHODS: A case-control study was carried
      out in the municipality of Caxias do Sul, Southern Brazil. Characteristics of
      prenatal care and causes of mortality were assessed for all live births in the
      2001-2002 period with a completed live-birth certificate and whose mothers lived
      in the municipality. Cases were defined as all deaths within the first year of
      life. As controls, there were selected the two children born immediately after
      each case in the same hospital, who were of the same sex, and did not die within
      their first year of life. Multivariate analysis was performed using conditional
      logistic regression. RESULTS: There was a reduction in infant mortality, the
      greatest reduction was observed in the post-neonatal period. The variables
      gestational age (<36 weeks), birth weight (<2,500 g), and 5-minute Apgar (<6)
      remained in the final model of the multivariate analysis, after adjustment.
      CONCLUSIONS: Perinatal conditions comprise almost the totality of neonatal
      deaths, and the majority of deaths occur at delivery. The challenge for reducing
      infant mortality rate in the city is to reduce the mortality by perinatal
      conditions in the neonatal period.

PMID- 16583036
TI  - [Lifetime prevalence and help seeking behavior in physical marital violence].
AB  - OBJECTIVE: To estimate the lifetime prevalence of physical marital violence among
      women from a low-income urban community and to investigate help-seeking behavior
      among victims. METHODS: This is the Brazilian pilot cross-sectional study for an
      international multicenter study conducted in 1999, and is based on a
      probabilistic cluster sample from the municipality of Embu, Sao Paulo State. We
      considered as eligible women aged 15 to 49 years, living with children under age
      18 years, who had lived with a husband or partner in lifetime. Information was
      collected using standardized questionnaires (n=86), administered by trained
      interviewers. We investigated three types of physical violence: severe (kicking,
      hitting with fist, beating, and/or use/threat to use weapon), non-severe
      (slapping in the absence of severe violence), and any type (severe and/or non
      severe and/or other physical aggressions spontaneously referred), as well as the
      type of help sought by the victim (from people or institutions). We calculated
      frequency and 95% confidence intervals for each type of violence. RESULTS:
      Subjects reported slapping (32.6%), hitting with fist (17.5%), beating (15,2%),
      use/threat to use weapon (13.9%), and kicking (10.6%). Prevalence of marital
      violence was high: 22.1% (13.3-30.9) for severe violence, 10.5% (4.0-17.0) for
      non-severe violence, and 33.7% (32.7-34.7) for any type of violence. Victims of
      severe violence were more likely to seek help from the police (36.8%) or from
      traditional healers (21.1%) than from health care facilities (5.3%), despite the
      availability of these services in the area. CONCLUSIONS: Physical marital
      violence is frequent and severe among the population studied, and help was sought
      preferentially from the police or traditional healers rather than from health
      care services.

PMID- 16583037
TI  - [Spatial distribution of M. tuberculosis-HIV coinfection in Sao Paulo State,
      Brazil, 1991-2001].
AB  - OBJECTIVE: To assess the spatial pattern of tuberculosis incidence in relation to
      the AIDS epidemic, with the aim of investigating the geographical influence on
      causality. METHODS: All AIDS cases from State of Sao Paulo, notified to the
      Brazilian Ministry of Health between 1991 and 2001, were included. The cases were
      stratified by municipality, by administrative health regions, AIDS transmission
      categories, gender and years since diagnosis. A Gaussian geostatistical model was
      used to construct a thematic risk map, utilizing the tuberculosis incidence among
      AIDS cases as the response variable. RESULTS: Exploratory analysis showed two
      patterns of AIDS incidence: one for the state capital, and another, with
      increasing risk, for the other municipalities. The more populous regions
      presented higher risk of tuberculosis transmission, with a pattern that matched
      the land occupation pattern, from east to west. The health regions with the
      highest AIDS incidence coefficients (per 10,000 inhabitants) were Santos (53.5),
      Sao Jose do Rio Preto (43.1), Ribeirao Preto (42.4) and Sao Paulo (40.3). The
      health regions with greatest tuberculosis incidence among AIDS cases were Santos
      (44.9%), Franco da Rocha (39.9%), Osasco (39.6%) and Sao Paulo (38.9%).
      CONCLUSIONS: The results allow the conclusion that geographical coordinates
      presented an association with tuberculosis risk, but not with AIDS risk.

PMID- 16583038
TI  - [Cancer mortality among rubber industry workers in Sao Paulo, Brazil].
AB  - OBJECTIVE: To investigate cancer deaths among rubber industry workers according
      to company size. METHODS: This historical cohort study included 9,188 male
      workers, engaged as members of a workers' union in Sao Paulo, Southeastern
      Brazil, between 1975 and 1985, alive in January 1990 and followed until the end
      of 2000. Overall and specific cancer deaths were compared within the cohort, with
      subjects stratified according to company size and economic activity, sector of
      work, and worker qualification. Risk set assessment and conditional logistic
      regression were used to estimate relative risks, adjusted for age, time since
      first job, and duration of employment in the rubber industry. RESULTS: When
      compared to employees of larger companies, workers employed in small companies
      showed greater risk of death due to any type of cancer (RR=2.33, 95% CI: 0.90
      6.03), stomach tumors (RR=3.47; 95% CI: 2.57-4.67), and upper aero-digestive
      tract tumors (RR=2.49; 95% CI: 1.78-3.48). Risk of death was greater among
      workers employed in maintenance (RR=2.23; 95% CI: 0.73-6.76); expedition, storage
      and transportation (RR=2.97; 95% CI: 0.77-11.38); and production (RR=3.51; 95%
      CI: 1.07-11.57), when compared to workers engaged in clerical work and support
      activities. CONCLUSIONS: Our results provide further evidence for an increased
      risk of stomach and upper aero-digestive tract tumors--and possibly of all types
      of cancer--among rubber industry workers employed in small companies when
      compared to employees of larger companies.

PMID- 16583039
TI  - [Factors associated with drug and alcohol use among university students].
AB  - OBJECTIVE: Recent studies show an alarming rate of alcohol and drug use among
      university students. The objective of this study was to assess the level of
      association between lifestyle and socioeconomic status and the prevalence of
      alcohol, tobacco, medicine, and "illicit drug" use in the last 12 months among
      university students. METHODS: The sample included 926 undergraduate students in
      the Biology Department of a university in Sao Paulo who completed an anonymous,
      self-applied questionnaire in 2000 and 2001. Anova and Chi-square tests were
      applied to verify the correlation between substance use and variables. RESULTS:
      Among students who reported having a religion, alcohol consumption was 83.1%,
      tobacco use 20.7%, and "illicit drugs" 24.6% during this period. Among students
      who reported not having a religion, reported alcohol use was higher in the last
      12 months: alcohol (89.3%), tobacco (27.7%) and "illicit drugs" (37.7%). Monthly
      family income was related to alcohol and "illicit drug" use (p<0.001 for both).
      The students who used tobacco and "illicit drugs" reported more free time during
      the week than students who didn't smoke during the period of time analyzed
      (p=0.033 and p=0.008, respectively). CONCLUSIONS: Psychoactive drug use was
      common among students, indicating a need for policies to be implemented with the
      goal of reducing consumption. Students with higher family income and without
      religion should be considered to be at higher risk for alcohol and drug use among
      this group.

PMID- 16583040
TI  - [Population-based study of the epidemiology of diagnostic test ordering].
AB  - OBJECTIVE: To identify type of service, frequency, and individual patient
      determinants associated with diagnostic test ordering in medical appointments.
      METHODS: A population-based study included 3,100 adults aged 20 years or older,
      living in the city of Pelotas, Southern Brazil. Sampling was carried out in
      multiple stages. Information were collected by means of a questionnaire,
      administered between October and December 2003. Multivariate analyses were
      carried out using Poisson Regression, based on a conceptual model. A sub-study
      was also conducted based on the test requests received during one workday in all
      laboratories in the city processing requests from both the public and private
      sectors. RESULTS: Fifty-five percent of subjects reported having had medical
      appointments during the three-month period investigated. Of these, 60% reported
      more than one appointment, generating a total 4,167 appointments, most of which
      were paid for by health plans (38%). Diagnostic test were requested in 55% of
      appointments. Women and diabetic patients were more likely to have tests ordered.
      The greater the age (p<0.001) the higher the socioeconomic level (p=0.04), and
      the number of medical appointments (p<0.001), the greater the proportion of
      appointments leading to test requests. Mean waiting time between test request and
      sample collection was six days for the private sector and 21 days for the public
      sector (p<0.001). The mean number of tests per request was 4.4. CONCLUSIONS: The
      proportion of appointments leading to the request for some type of diagnostic
      test was in accordance with Brazilian recommendations. The waiting time before
      sample collection indicates an excessive number of tests per request and/or
      insufficient financial resources to fulfill the demand for tests.

PMID- 16583041
TI  - [Health-related quality of life in Spanish women with osteoporosis].
AB  - OBJECTIVE: To analyze the health-related quality of life in patients with
      osteoporosis and to compare it with the overall population. METHODS: A cross
      sectional descriptive study was carried out with 60 female patients of the
      rheumatology service at a university hospital, in Spain, from April to October
      2003. The Short Form-36 (SF-36) questionnaire was applied in order to obtain
      demographic data, clinical characteristics and data about lifestyles related to
      health. Patients were classified in age groups. The statistics tests performed
      were Chi-square, general linear model, Student's t-test. RESULTS: The
      interviewees' average age was 65.57 years old (SD: +/- 9.7 years), and average
      time interval for diagnosis was 3.4 +/- 2.84 years. The best scores were in
      social functioning (89), emotional aspects (72.2), mental health (63), and
      vitality (53.7). The lowest scores were in general health (45.1), physical
      capacity (47.7), pain (52.3) and physical aspects (59.9). The patients' average
      scores were lower than the general Spanish population's scores in the following
      dimensions: functional capacity, physical aspects, pain and overall health
      status. The greatest differences between the average SF-36 scores for patients
      and for the overall Spanish population were in the age group ranging from 55 to
      64 years old. Scores were lower or similar to the general Spanish population in
      all other dimensions of the questionnaire. No significant associations were found
      between the dimensions of the SF-36 contemplated in this study and the clinical,
      demographic and lifestyle data. CONCLUSIONS: The patients presented bad quality
      of life, particularly with respect to those dimensions that are most relevant
      with respect to osteoporosis, when compared with the overall Spanish population.
      The physical dimensions were the ones most affected.

PMID- 16583042
TI  - Cost of schizophrenia: direct costs and use of resources in the State of Sao
      Paulo.
AB  - OBJECTIVE: To estimate the direct costs of schizophrenia for the public sector.
      METHODS: A study was carried out in the state of Sao Paulo, Brazil, during 1998.
      Data from the medical literature and governmental research bodies were gathered
      for estimating the total number of schizophrenia patients covered by the
      Brazilian Unified Health System. A decision tree was built based on an estimated
      distribution of patients under different types of psychiatric care. Medical
      charts from public hospitals and outpatient services were used to estimate the
      resources used over a one-year period. Direct costs were calculated by
      attributing monetary values for each resource used. RESULTS: Of all patients,
      81.5% were covered by the public sector and distributed as follows: 6.0% in
      psychiatric hospital admissions, 23.0% in outpatient care, and 71.0% without
      regular treatment. The total direct cost of schizophrenia was US $191,781,327
      (2.2% of the total health care expenditure in the state). Of this total, 11.0%
      was spent on outpatient care and 79.2% went for inpatient care. CONCLUSIONS: Most
      schizophrenia patients in the state of Sao Paulo receive no regular treatment.
      The study findings point out to the importance of investing in research aimed at
      improving the resource allocation for the treatment of mental disorders in
      Brazil.

PMID- 16583043
TI  - [Eating behavior among type 2 diabetes women].
AB  - OBJECTIVE: To explore type 2 diabetes women's thoughts, feelings and behaviors
      concerning diet. METHODS: A descriptive, exploratory qualitative study was
      carried out among eight type 2 diabetes women from a primary health care unit in
      Southeastern Brazil in January 2003. A semi-structured interview was applied for
      data collection. The theoretical reference was the theory of social
      representations. The interviews were recorded, transcribed and then their
      thematic content was analyzed. RESULTS: The study results showed women's
      difficulty in following the prescribed diet due to several associated meanings,
      such as loss of eating and drinking pleasure and loss of eating autonomy and free
      choice. Following the diet elicits an extremely aversive and restrictive
      attitude, and complying with it is associated to damage to health. The frequent
      absence of symptoms was mentioned as one reason that prevents compliance to the
      diet. Other difficulties reported were touching, looking at, and handling foods
      during their preparation but not being allowed to eat them. Sweet foods revealed
      to be extremely desired. Transgression and food desire are equally present in
      their life. Following the recommended diet brings sadness and the act of eating
      is frequently accompanied by fear, guilt and anger. CONCLUSIONS: Type 2 diabetes
      women's eating behavior is very complex and needs to be understood from its
      psychological, biological, social, cultural and economic aspects for promoting
      more effective educational interventions.

PMID- 16583044
TI  - [Continuing or discontinuing BCG revaccination in adolescents].
AB  - BCG revaccination was introduced in Brazil in the mid-90's but no study has
      evaluated vaccine coverage through direct assessment of the scar. BCG scars were
      assessed in 2,785 public school adolescents, aged 13 to 14 years, in Southeastern
      Brazil, between September 2001 and May 2002. The prevalence rate of revaccination
      was 64.3% (95% CI: 62.5-66.0). Despite the efforts to implement and sustain
      revaccination, continuing this practice should be reevaluated by public health
      authorities due to the lack of evidence on its effectiveness.

PMID- 16583045
TI  - [Intestinal parasitic helminths in institutionalized dogs of Rio de Janeiro,
      Brazil].
AB  - The occurrence of intestinal parasitic helminths in dogs from a public institute
      of veterinary medicine in Rio de Janeiro was assessed. Samples of fresh feces
      were collected in March 2004 and analyzed by Willis and centrifugal-flotation in
      sucrose solution methods. Of 204 samples, 45.6% were positive for helminths.

PMID- 16583046
TI  - Phlebotomine fauna in a rural area of the Brazilian Pantanal.
AB  - The aim of the study was to identify among the phlebotomine fauna potential
      leishmaniasis vectors. The study was carried out in Corumba county, State of Mato
      Grosso do Sul, Mid-West Brazil (18 degrees 59' S, 56 degrees 39' W). Sand fly
      captures were undertaken fortnightly with automatic light traps at 11 sites in
      forested environments and anthropic areas from April 2001 to July 2003. A total
      of only 41 specimens were captured. Thirty-one percent of the specimens were
      captured in forests and 68.3% in anthropic areas. The predominance of non
      anthropophilic groups and the low density of N. whitmani, a known cutaneous
      leishmaniasis vector, does not seem to indicate any actual risk of the
      transmission of this disease in the study area.

PMID- 16583047
TI  - [Preliminary information on sandflies in the north of Parana State, Brazil].
AB  - The results from sandfly collections in 10 municipalities in Parana State, Brazil
      are reported. The captures were done using Falcao traps in homes, domestic animal
      shelters and forested areas, from 1999 to 2002. A total of 13,653 sandflies were
      collected from 10 species of the genera Brumptomyia, Expapillata, Evandromyia,
      Migonemyia, Pintomyia, Nyssomyia and Psathyromyia. The species Nyssomyia neivai
      was predominant in five municipalities. N. whitmani predominated in the other
      five, in greater numbers than for N. neivai in the first five municipalities.
      High frequencies of sand flies were found in forests, homes, pigpens and
      henhouses. Investigations on the participation of domestic animals and
      phlebotomine fauna in the epidemiology of tegumentary leishmaniasis should be
      routine in health surveillance, especially where this disease is endemic.

PMID- 16583048
TI  - Worldwide molecular epidemiology of HIV.
AB  - Human immunodeficiency virus (HIV) is the worldwide disseminated causative agent
      of acquired immunodeficiency syndrome (AIDS). HIV is a member of the Lentivirus
      genus of Retroviridae family and is grouped in two types named HIV-1 and HIV-2.
      These viruses have a notable ability to mutate and adapt to the new conditions of
      human environment. A large incidence of errors at the transcriptional level
      results in changes on the genetic bases during the reproductive cycle. The
      elevated genomic variability of HIV has carried important implications for the
      diagnosis, treatment and prevention as well as epidemiologic investigations. The
      present review describes important definitions and geographical distribution of
      subtypes, circulating recombinant forms and other genomic variations of HIV. The
      present study aimed at leading students of Biomedical Sciences and public health
      laboratory staff guidance to general and specific knowledge about the genomic
      variability of the HIV.

PMID- 16583049
TI  - [Health promotion groups for improving autonomy, living conditions and health].
AB  - This article presents the methodology of Health Promotion Groups, which were
      conceived as a means of contributing towards developing autonomy, improving
      living conditions and promoting health. The method is identified as a collective
      and interdisciplinary health intervention, consisting of a group process. It
      guides the development of attitudes and behavioral patterns towards continually
      transforming participants' health levels and living conditions. The Health
      Promotion Groups are identified within the context of the National Health System
      (Sistema Unico de Saude) as a means of surpassing the biomedical model. It
      stimulates the development of actions in which the positive aspects of health are
      emphasized, while at the same time it can serve to more effectively meet the
      demands for care for the elderly in health systems.

PMID- 16583050
TI  - [Low birth weight and periodontal disease association].

PMID- 16583051
TI  - [Vaccine against rotavirus].

PMID- 16583052
TI  - [Pharmaceutical input].

PMID- 16583053
TI  - [Pesticide residues in food].

PMID- 16583056
TI  - Muscular subunits transplantation for facial reanimation.
AB  - PURPOSE: To present an alternative technique for reconstruction of
      musculocutaneous damages in the face transferring innervated subsegments
      (subunits) of the latissimus dorsi flap for replacement of various facial mimetic
      muscles. METHODS: One clinical case of trauma with skin and mimetic muscles
      damage is described as an example of the technique. The treatment was performed
      with microsurgical transfer of latissimus dorsi muscle subunits. Each subunit
      present shape and dimensions of the respective mimetic muscles replaced. The
      origin, insertions and force vectors for the mimic muscle lost were considered.
      Each subsegment has its own arterial and venous supply with a motor nerve
      component for the muscular unit. RESULTS: Pre and one year postoperative photos
      registration of static and dynamic mimic aspects, as well as digital
      electromyography digital data of the patients were compared. The transplanted
      muscular units presented myoelectric activity, fulfilling both the functional and
      cosmetic aspect. CONCLUSION: This technique seems to be a promising way to deal
      with the complex musculocutaneous losses of the face as well as facial palsy.

PMID- 16583057
TI  - Basal cell carcinoma: an updated epidemiological and therapeutically profile of
      an urban population.
AB  - PURPOSE: To describe the epidemiological profile of basal cell carcinoma patients
      at a private hospital in Sao Paulo and to evaluate the treatment adopted.
      METHODS: A prospective study of 202 patients, on which 253 lesions were diagnosed
      for histopathological exam as basal cell carcinoma within the period of January
      2001 to September 2003, in the Plastic Surgery Residency Program at the Hospital
      Jaragua. The susceptibility factor of the host, the environment variables, the
      characteristics of the lesions and the efficacy of the treatment were examined.
      The data were statistically evaluated. RESULTS: The incidence of basal cell
      carcinoma was 126 cases per 100,000 patients in a period of 32 months (36 cases
      per 100,000 patients/year). The patients were evenly distributed in terms of sex:
      48% male and 52% female. The greater incidence was in patients between the ages
      of 60 and 80 years and the average was 64 years. The survey revealed
      susceptibility factors such as white race and phototypes I and II in 95.5% of the
      patients. Exposition to ultraviolet radiation was reported by 77% of the patients
      and the most frequent location of tumors was on the face (71.2% of the cases).
      Actinic keratosis and a history of skin cancer were reported in 43.6% and in 25%
      of the cases, respectively. The adopted treatment was surgery in 99.4% of the
      cases and only one patient was treated with radiotherapy. Twenty lesions (8%) had
      incomplete excision. The recurrence rate was 2% (5 cases). There were no cases
      with metastasis or fatal outcome. CONCLUSIONS: The factors related to the
      development of basal cell cancer which were significantly present in the
      population surveyed were: older age, white individuals, phototypes I and II,
      presence of actinic keratosis, previous history of non-melanoma skin cancer and
      exposure to ultra-violet rays both in recreational and in occupational form. The
      surgical treatment employed was effective with a rate of incomplete excision and
      recurrence similar to those found in the literature.

PMID- 16583059
TI  - The role of ischemic preconditioning at the gracilis muscle of rats in the early
      phase of reperfusion injury.
AB  - PURPOSE: Verify the role of ischemic preconditioning (IPC) in ischemia and
      reperfusion injury on gracilis muscle of rats. METHODS: Wistar rats (n=30) were
      distributed in three groups, I/R and IPC groups were subdivided concerning
      ischemia time. A near-amputation model of the posterior limb was produced by a
      hip joint level incision, preserving the vascular bundle and the femur bone and
      ischemia was induced for 2 h and 4 h, G-I 2 h/R (n=6) and G-I 4 h/R (n=6),
      followed by 1 h of vascular reperfusion. The preconditioned groups, G-PCI 2 h
      (n=6) and G-PCI 4 h (n=6), were preceded by 3 cycles of 5 min of ischemia
      followed by 5 min of vascular reperfusion before sustained ischemia. In the
      Control Group, C-G (n=6) animals were subjected to regional approach. The
      analysis was done with Light Microscopy (LM). RESULTS: The levels of fibril
      fragmentation were progressive in the G-I 2 h/R (67% of muscle preservation) and
      in the G-I 4 h/R (0% of muscle preservation). However in the group of the
      precondition the lesion degree being in level similar to the group controls in
      the G-I 2 h/R (100% of muscle preservation) while at G-I 4 h/r occur less
      protection (67% of muscle preservation). The degree of tissue inflammatory
      reaction was worst at G-I 4 h/R (0% without inflammation signals) than at G-I 2
      h/R (50% without inflammation signals); while in the precondition group G-IPC-2 h
      (83% without inflammation signals) was better than the G-IPC-4 h (67% without
      inflammation signals). The vascular stasis was absent only in 17% of the G-I 4
      h/R and in 33% of the G-I 2 h/R. In precondition group, however, the vascular
      stasis was absent in 33% at G-IPC 2 h and absent in 50% at G-IPC 4 h. CONCLUSION:
      The IPC showed, in an earlier phase, a beneficial role at I/R derived injury on
      gracilis muscle of rats, as proven for the largest preservation of the fibers
      muscular, smaller inflammatory reaction and smaller vascular stasis.

PMID- 16583058
TI  - Influence of laparoscopy and laparotomy on gasometry, leukocytes and cytokines in
      a rat abdominal sepsis model.
AB  - PURPOSE: Laparoscopic surgery is associated with reduced surgical trauma, and
      less acute phase response, as compared with open surgery. Cytokines are important
      regulators of the biological response to surgical and anesthetic stress. The aim
      of this study was to determine if CO2 pneumoperitoneum would change cytokine
      expression, gas parameters and leukocyte count in septic rats. METHODS: Wistar
      rats were randomly assigned to five groups: control (anesthesia only),
      laparotomy, CO2 pneumoperitoneum, cecum ligation and puncture by laparotomy, and
      laparoscopic cecum ligation and puncture. After 30 min of the procedures,
      arterial blood samples were obtained to determine leukocytes subpopulations by
      hemocytometer. TNFalpha, IL-1beta, IL-6 were determined in intraperitoneal fluid
      (by ELISA). Gas parameters were measured on arterial blood, intraperitoneal and
      subperitoneal exudates. RESULTS: Peritoneal TNFalpha, IL-1beta and IL-6
      concentrations were lower in pneumoperitoneum rats than in all other groups
      (p<0.05). TNFalpha, IL-1beta and IL-6 expression was lower in the laparoscopic
      than in laparotomic sepsis (p<0.05). Rats from laparoscopic cecum ligation and
      puncture group developed significant hypercarbic acidosis in blood and
      subperitoneal fluid when compared to open procedure group. Total white blood
      cells and lymphocytes were significantly lower in laparoscopic cecum ligation and
      puncture rats than in the laparotomic (p<0.01). Nevertheless, the laparotomic
      cecum ligation rats had a significant increase in blood neutrophils and
      eosinophils when compared with controls (p<0.05). CONCLUSIONS: This study
      demonstrates that the CO2 pneumoperitoneum reduced the inflammatory response in
      an animal model of peritonitis with respect to intraperitoneal cytokines, white
      blood cell count and clinical correlates of sepsis. The pneumoperitoneum produced
      hypercarbic acidosis in septic animals.

PMID- 16583060
TI  - The number of podocyte and slit diaphragm is decreased in experimental diabetic
      nephropathy.
AB  - PURPOSE: To determine the number of podocyte, slit diaphragms, slit diaphragm
      extensions and GBM thickness in diabetic nephropathy. METHODS: Sixty "Rattus
      Wistar"of both sexes weighing 200-300 g were divided in two experimental groups:
      normal group 10 animals, and alloxan diabetic rats--50 animals. Alloxan was
      administered in a single IV dose of 42 mg/kg body weight. Body weight, water and
      food intake, diuresis, and blood and urine glucose were determined in both groups
      before alloxan injection and two weeks, six and twelve months after alloxan
      injection. Proteinuria was measured at 12 months in both groups. After 12 months
      animals were sacrificed, and the right kidney processed for electron microscopy.
      RESULTS: Clear clinical and laboratory signs of severe diabetes were seen, in all
      alloxan-diabetic rats at all follow-up times. Glomerular basement membrane (GBM)
      thickening, podocyte number, and slit diaphragm number and extension were
      determined. GBM of all diabetic rats was significantly thicker (median=0.29
      microm; semi-interquartile range=0.065 microm) than in the normal rats (0.23
      microm; 0.035 microm). Diabetic rat podocyte number (8; 1), slit diaphragm number
      (4; 1), and slit diaphragm extension (0.021 microm; 0.00435 microm) were
      significantly lower than in normal rats (11; 1) and (7; 1.5), and (0.031 microm;
      0.0058 microm). Diabetic rat proteinuria (0.060 mg/24 h; 0.037 mg/24 h) was
      higher than in normal rats (0.00185 mg/24 h; 0.00055 mg/24 h). CONCLUSION:
      Experimental diabetes is associated with significant (p<0.05) changes in podocyte
      foot process, slit number, slit diaphragm extension, and GBM thickness.

PMID- 16583061
TI  - Medial meniscus transplantation using cyanoacrylate in rabbits.
AB  - PURPOSE: To evaluate meniscal transplantation using as fixation method a
      synthetic glue derived from cyanoacrylate acid. METHODS: Twenty rabbits were
      used, of which 10 for autologous transplantation and 10 for homologous
      transplantation. For the autologous transplantation the meniscus was removed, and
      then transplanted in the same animal, using the synthetic glue. For the
      homologous transplantation, the study was divided into two stages: 1--Removal of
      the meniscus which was maintained at a temperature of 73 C. 2--Use of
      cyanoacrylate acid-derived surgical adhesive for meniscal retransplantation in a
      different rabbit 30 days after the transplant. RESULTS: Due to complications,
      euthanasia had to be anticipated to the 15th day in the homologous group and to
      the 18th day in the autologous group. Macroscopically, knees submitted to
      transplantation presented whitish secretions from the surgical incision up to
      deep planes. Necrosis was observed in both groups. Statistical analysis has shown
      that mild (p=0.043) and moderate (p=0.001) complications emerged in a
      significantly earlier way in the homologous group, where euthanasia was also
      performed earlier (p=0.005). CONCLUSION: Synthetic surgical adhesives derived
      from cyanoacrylate acid promoted cortical to medullary bone necrosis bone in both
      groups.

PMID- 16583062
TI  - Comparative study of descendent colon rupture resistance considering traction
      force of rupture and total energy of rupture in rats.
AB  - PURPOSE: To compare total energy of rupture and traction force of rupture tests
      within a rupture resistance study of descendent colon of rats. METHODS: Twelve
      descendent colon segments of rats were considered to perform the study. For each
      one of the specimens, total energy of rupture and traction force of rupture
      necessary to promote colic wall burst were evaluated through the biomechanical
      total energy of rupture test using the Biomechanical Data Acquisition and
      Analysis System, version 2.0. Average, standard deviation, standard error of
      average and coefficient of variation were considered for analysis of results.
      RESULTS: Traction force of rupture average, standard deviation, standard error of
      average and coefficient of variation were 380.05 gf, 98.74, 28.5 e 25.98%,
      respectively while total energy of rupture presented average of 244.85 gf,
      standard deviation of 57.76, standard error of average of 16.67 and coefficient
      of variation of 23.59. CONCLUSION: Although, total energy of rupture considered a
      larger number of attributes to its calculation related to non-linear viscoelastic
      materials, such as colic wall, it presented a smaller coefficient of variation
      when compared to traction force of rupture, thus demonstrating to constitute a
      possible parameter to analyze intestinal resistance of rats.

PMID- 16583063
TI  - [A novel model for isolation of Walker's tumoral cells using the Ficoll-Hypaque
      gradient].
AB  - PURPOSE: The purpose was to evaluate a novel technique for isolation of Walker's
      tumoral cells using a Ficoll-Hypaque gradient and its further influence on tumor
      development. METHODS: Twenty male Wistar rats have been divided in 2 groups: G1=
      without ficoll, G2= with ficoll. Tumor was excised, homogenized and suspended in
      lactate ringer. A sample of the cell suspension was adjusted at a concentration
      of 1x10(6) cells/ml (G1). A second sample was centrifuged on a Ficoll-Hypaque
      gradient and the cell concentration was then adjusted (G2). Tumor was implanted
      by subcutaneous injection of 1.0 ml in the right armpit of rats. Tumor volume
      (TV) and tumor weight (TW) were compared in two groups. RESULTS: There were no
      differences between the two groups in TV (G1=17.9+/-3.8 cm3 vs. G2=17.2+/-4.4
      cm3; p=0.190) and TW (G1=7.0+/-1.8 g vs. G2=7.3+/-2.8 g; p=0.569). The
      histological analysis showed similar patterns of infiltration by small
      undifferentiated cells and necrosis in both groups. However, a mild to moderate
      granulocytic exudate was more frequent in the animals whose tumors derived from
      Ficoll-isolated cells. Hemorrhage from slight to moderate was only observed in
      this group. CONCLUSION: A Ficoll-Hypaque gradient can provide more adequate
      isolation of Walker's tumor and the cell suspension obtained by this technique
      has lower contamination by other cell types.

PMID- 16583064
TI  - [Early effects of 7.5% hypertonic saline solution on splanchnic perfusion after
      hemorrhagic shock].
AB  - PURPOSE: To evaluate the effects of SSH resuscitation on systemic and splanchnic
      hemodynamic variables in an experimental model of controlled hemorrhagic shock.
      METHODS: Ten mongrel dogs were bled (20 ml/min) to a target mean arterial
      pressure (MAP) of 40+/-5 mmHg. After 30 minutes of shock, animals received SSH
      infused in 5-minute and they were observed for 60 minutes thereafter. Systemic
      hemodynamics were evaluated through a Swan-Ganz and arterial catheters while
      gastrointestinal tract perfusion by a catheter inside the portal vein, an
      ultrasonic flowprobe around portal vein blood flow (PVBF) and a gastric
      tonometer. Splanchnic oxygen delivery and consumption, intramucosal pH and veno
      arterial, portal-arterial and mucosal-arterial pCO2-gradients (D(ap-a)pCO2, D(vp
      a)pCO2 e D(t-a)pCO2, respectively) were assessed. RESULTS: Hemorrhage (29.8+/-2.4
      ml/Kg) induced significant decreases in MAP (125+/-6 to 42+/-1 mmHg), in CO
      (1.9+/-0.2 to 0.6+/-0.1 L/min), and PVBF (504+/-73 to 126+/-12 ml/min) while
      significant increases were detected in D(ap-a)pCO2 (5.3+/-0.8 to 19.9+/-1.6 mmHg)
      D(vp-a)pCO2 (5.4+/-1.4 to 22.6+/-2.1 mmHg) and D(t-a)pCO2 (6.1+/-1.1 to 43.8+/
      7.5 mmHg). SSH infusion promoted only partial benefits in systemic and splanchnic
      blood flows. Reduced pCO2 gradients but fewer effects in D(t-a)pCO2 were
      observed. CONCLUSION: The SSH infusion promoted partial systemic and splanchnic
      hemodynamic benefits. Those benefits were especially poor at the splanchnic
      microcirculation, as evaluated by D(t-a)pCO2. In addition, systemic and regional
      oxygen-derived variables do not reflect the regional microcirculation
      disturbances. Gastrointestinal tonometry clearly represents a useful tool for
      monitoring splanchnic perfusion in patients in hemodynamic shock.

PMID- 16583066
TI  - Making deaths count.

PMID- 16583065
TI  - [Evaluation of an experimental model of necrotizing enterocolitis in rats].
AB  - OBJECTIVE: To evaluate an experimental model of necrotizing enterocolitis in rats
      proposed by OKUR e col. in 1995. METHODS: On their first day of life, 28 EPM
      Wistar rats weighing between 4 and 6 grams were submitted to hypoxia (H) by
      placing them in a CO2 gas chamber for rodents' sacrifice, where they received a
      100% CO2 air flow for 5 minutes. After the hypoxia the animals were reanimated
      (R) with a 100% O2 air flow, also for 5 minutes. The animals were allocated in
      two groups: G1: control (n=12): rats not submitted to H-R; G2: (n=16): rats
      submitted to H-R. Segments of the small intestine and colon were prepared for
      histological analysis. The remaining intestine was used to measure tissular
      malondialdehyde. RESULTS: Mean malondialdehyde dosages were 1.05 (0.44-2.03) and
      2.60 (0.59- 6.4) nmol MDA/mg protein for G1 and G2, respectively. G2's mean value
      was significantly higher than in the control group (p<0.002). Significant
      statistical difference between the studied groups was found in relation the level
      of injury, with G1 presenting significantly lower levels than G2. CONCLUSIONS:
      The model showed that neonatal hypoxia may cause intestinal wall injury in rats.
      Despite the discreet histological injuries found, the method is suitable for
      evaluation of tissular free radicals.

PMID- 16583067
TI  - Demographic Surveillance Sites and emerging challenges in international health.

PMID- 16583068
TI  - Potential and limits of verbal autopsies.

PMID- 16583069
TI  - Malaria deaths are the hardest to count.

PMID- 16583070
TI  - Mexico's quest for a complete mortality data set.

PMID- 16583071
TI  - Counting the dead in China.

PMID- 16583072
TI  - Counting the dead is essential for health.

PMID- 16583074
TI  - Tobacco Convention: countries "changed history".

PMID- 16583075
TI  - How should we measure maternal mortality in the developing world? A comparison of
      household deaths and sibling history approaches.
AB  - OBJECTIVE: A reduction in the maternal mortality ratio (MMR) is one of six health
      related Millennium Development Goals (MDGs). However, there is no consensus about
      how to measure MMR in the many countries that do not have complete registration
      of deaths and accurate ascertainment of cause of death. In this study, we
      compared estimates of pregnancy-related deaths and maternal mortality in a
      developing country from three different household survey measurement approaches:
      a module collecting information on deaths of respondents' sisters; collection of
      information about recent household deaths with a time-of-death definition of
      maternal deaths; and a verbal autopsy instrument to identify maternal deaths.
      METHODS: We used data from a very large nationally-representative household
      sample survey conducted in Bangladesh in 2001. A total of 104 323 households were
      selected for participation, and 99 202 households (95.1% of selected households,
      98.8% of contacted households) were successfully interviewed. FINDINGS: The
      sisterhood and household death approaches gave very similar estimates of all
      cause and pregnancy-related mortality; verbal autopsy gave an estimate of
      maternal deaths that was about 15% lower than the pregnancy-related deaths. Even
      with a very large sample size, however, confidence intervals around mortality
      estimates were similar for all approaches and exceeded +/- 15%. CONCLUSION: Our
      findings suggest that with improved training for survey data collectors, both the
      sisterhood and household deaths methods are viable approaches for measuring
      pregnancy-related mortality. However, wide confidence intervals around the
      estimates indicate that routine sample surveys cannot provide the information
      needed to monitor progress towards the MDG target. Other approaches, such as
      inclusion of questions about household deaths in population censuses, should be
      considered.

PMID- 16583077
TI  - Assessing adult mortality in HIV-1-afflicted Zimbabwe (1998 -2003).
AB  - OBJECTIVE: To compare alternative methods to vital registration systems for
      estimating adult mortality, and describe patterns of mortality in Manicaland,
      Zimbabwe, which has been severely affected by HIV. METHODS: We compared estimates
      of adult mortality from (1) a single question on household mortality, (2)
      repeated household censuses, and (3) an adult cohort study with linked HIV
      testing from Manicaland, with a mathematical model fitted to local age-specific
      HIV prevalence (1998 -2000). FINDINGS: The crude death rate from the single
      question (29 per 1000 person-years) was roughly consistent with that from the
      mathematical model (22 -25 per 1000 person-years), but much higher than that from
      the household censuses (12 per 1000 person-years). Adult mortality in the
      household censuses (males 0.65; females 0.51) was lower than in the cohort study
      (males 0.77; females 0.57), while mathematical models gave a much higher
      estimate, especially for females (males 0.80 -0.83; females 0.75 -0.80). The
      population attributable fraction of adult deaths due to HIV was 0.61 for men and
      0.70 for women, with life expectancy estimated to be 34.3 years for males and
      38.2 years for females. CONCLUSION: Each method for estimating adult mortality
      had limitations in terms of loss to follow-up (cohort study), under-ascertainment
      (household censuses), transparency of underlying processes (single question), and
      sensitivity to parameterization (mathematical model). However, these analyses
      make clear the advantages of longitudinal cohort data, which provide more
      complete ascertainment than household censuses, highlight possible inaccuracies
      in model assumptions, and allow direct quantification of the impact of HIV.

PMID- 16583076
TI  - Cause-specific mortality rates in sub-Saharan Africa and Bangladesh.
AB  - OBJECTIVE: To provide internationally comparable data on the frequencies of
      different causes of death. METHODS: We analysed verbal autopsies obtained during
      1999 -2002 from 12 demographic surveillance sites in sub-Saharan Africa and
      Bangladesh to find cause-specific and age-specific mortality rates. The cause-of
      death codes used by the sites were harmonized to conform to the ICD-10 system,
      and summarized with the classification system of the Global Burden of Disease
      2000 (Version 2). FINDINGS: Causes of death in the African sites differ strongly
      from those in Bangladesh, where there is some evidence of a health transition
      from communicable to noncommunicable diseases, and little malaria. HIV dominates
      in causes of mortality in the South African sites, which contrast with those in
      highly malaria endemic sites elsewhere in sub-Saharan Africa (even in
      neighbouring Mozambique). The contributions of measles and diarrhoeal diseases to
      mortality in sub-Saharan Africa are lower than has been previously suggested,
      while malaria is of relatively greater importance. CONCLUSION: The different
      patterns of mortality we identified may be a result of recent changes in the
      availability and effectiveness of health interventions against childhood cluster
      diseases.

PMID- 16583078
TI  - Correcting for numerator/denominator bias when assessing changing inequalities in
      occupational class mortality, Australia 1981 -2002.
AB  - OBJECTIVE: Comparisons of the changing patterns of inequalities in occupational
      mortality provide one way to monitor the achievement of equity goals. However,
      previous comparisons have not corrected for numerator/denominator bias, which is
      a consequence of the different ways in which occupational details are recorded on
      death certificates and on census forms. The objective of this study was to
      measure the impact of this bias on mortality rates and ratios over time. METHODS:
      Using data provided by the Australian Bureau of Statistics, we examined the
      evidence for bias over the period 1981 -2002, and used imputation methods to
      adjust for this bias. We compared unadjusted with imputed rates of mortality for
      manual/non-manual workers. FINDINGS: Unadjusted data indicate increasing
      inequality in the age-adjusted rates of mortality for manual/non-manual workers
      during 1981 -2002. Imputed data suggest that there have been modest fluctuations
      in the ratios of mortality for manual/non-manual workers during this time, but
      with evidence that inequalities have increased only in recent years and are now
      at historic highs. CONCLUSION: We found that imputation for missing data leads to
      changes in estimates of inequalities related to social class in mortality for
      some years but not for others. Occupational class comparisons should be imputed
      or otherwise adjusted for missing data on census or death certificates.

PMID- 16583079
TI  - Assessing a new approach to verbal autopsy interpretation in a rural Ethiopian
      community: the InterVA model.
AB  - OBJECTIVE: Verbal autopsy (VA) -- the interviewing of family members or
      caregivers about the circumstances of a death after the event -- is an
      established tool in areas where routine death registration is non-existent or
      inadequate. We assessed the performance of a probabilistic model (InterVA) for
      interpreting community-based VA interviews, in order to investigate patterns of
      cause-specific mortality in a rural Ethiopian community. We compared results with
      those obtained after review of the VA by local physicians, with a view to
      validating the model as a community-based tool. METHODS: Two-hundred and eighty
      nine VA interviews were successfully completed; these included most deaths
      occurring in a defined community over a 1-year period. The VA interviews were
      interpreted by physicians and by the model, and cause-specific mortality
      fractions were derived for the whole community and for particular age groups
      using both approaches. FINDINGS: The results of the two approaches to
      interpretation correlated well in this example from Ethiopia. Four major cause
      groups accounted for over 60% of all mortality, and patterns within specific age
      groups were consistent with expectations for an underdeveloped high-mortality
      community in sub-Saharan Africa. CONCLUSION: Compared with interpretation by
      physicians, the InterVA model is much less labour intensive and offers 100%
      consistency. It is a valuable new tool for characterizing patterns of cause
      specific mortality in communities without death registration and for comparing
      patterns of mortality in different populations.

PMID- 16583080
TI  - Making COD statistics useful for public health at local level in the city of Cape
      Town: utilidad para la salud publica a nivel local en Ciudad del Cabo.
AB  - OBJECTIVE: To review the quality of the coding of the cause of death (COD)
      statistics and assess the mortality information needs of the City of Cape Town.
      METHODS: Using an action research approach, a study was set up to investigate the
      quality of COD information, the accuracy of COD coding and consistency of coding
      practices in the larger health subdistricts. Mortality information needs and the
      best way of presenting the statistics to assist health managers were explored.
      FINDINGS: Useful information was contained in 75% of death certificates, but
      nearly 60% had only a single cause certified; 55% of forms were coded accurately.
      Disagreement was mainly because routine coders coded the immediate instead of the
      underlying COD. An abridged classification of COD, based on causes of public
      health importance, prevalent causes and selected combinations of diseases was
      implemented with training on underlying cause. Analysis of the 2001 data
      identified the leading causes of death and premature mortality and illustrated
      striking differences in the disease burden and profile between health
      subdistricts. CONCLUSION: Action research is particularly useful for improving
      information systems and revealed the need to standardize the coding practice to
      identify underlying cause. The specificity of the full ICD classification is
      beyond the level of detail on the death certificates currently available. An
      abridged classification for coding provides a practical tool appropriate for
      local level public health surveillance. Attention to the presentation of COD
      statistics is important to enable the data to inform decision-makers.

PMID- 16583081
TI  - Facility-based maternal death reviews: effects on maternal mortality in a
      district hospital in Senegal.
AB  - OBJECTIVE: The improvement of obstetric services is one of the key components of
      the Safe Motherhood Programme. Reviewing maternal deaths and complications is one
      method that may make pregnancy safer, but there is no evidence about the
      effectiveness of this strategy. The objective of our before and after study is to
      assess the effect of facility-based maternal deaths reviews (MDR) on maternal
      mortality rates in a district hospital in Senegal that provides primary and
      referral maternity services. METHODS: We included all women who were admitted to
      the maternity unit for childbirth, or within 24 hours of delivery. We recorded
      maternal mortality during a 1-year baseline period from January to December 1997,
      and during a 3-year period from January 1998 to December 2000 after MDR had been
      implemented. Effects of MDR on organization of care were qualitatively evaluated.
      FINDINGS: The MDR strategy led to changes in organizational structure that
      improved life-saving interventions with a relatively large financial contribution
      from the community. Overall mortality significantly decreased from 0.83 (95% CI
      (confidence interval) = 0.60 -1.06) in baseline period to 0.41 (95% CI = 0.25 
      0.56) per 100 women 3 years later. CONCLUSION: MDR had a marked effect on
      resources, management and maternal outcomes in this facility. However, given the
      design of our study and the local specific context, further research is needed to
      confirm the feasibility of MDR in other settings and to confirm the benefits of
      this approach for maternal health in developing countries.

PMID- 16583082
TI  - Tracking progress towards the Millennium Development Goals: reaching consensus on
      child mortality levels and trends.
AB  - The increased attention to tracking progress towards the Millennium Development
      Goals (MDG), including Goal 4 of reducing child mortality, has drawn attention to
      a number of interrelated technical, operational and political challenges and to
      the underlying weaknesses of country health information systems upon which
      reliable monitoring depends. Assessments of child mortality published in 2005,
      for almost all low-income countries, are based on an extrapolation of the trends
      observed during the 1990s, rather than on the empirical data for more recent
      years. The validity of the extrapolation depends on the quality and quantity of
      the data used, and many countries lack suitable data. In the long run, it is
      hoped that vital registration or sample registration systems will be established
      to monitor vital events in a sustainable way. However, in the short run, tracking
      child mortality in high-mortality countries will continue to rely on household
      surveys and extrapolations of historical trends. This will require more
      collaborative efforts both to collect data through initiatives to strengthen
      health information systems at the country level, and to harmonize the estimation
      process. The latter objective requires the continued activity of a coordinating
      group of international agencies and academics that aims to produce transparent
      estimates -- through the consistent application of an agreed-upon methodology -
      for monitoring at the international level.

PMID- 16583083
TI  - A critical assessment of mortality statistics in Thailand: potential for
      improvements.
AB  - This study evaluates the collection and flow of mortality and cause-of-death
      (COD) data in Thailand, identifying areas of weakness and presenting potential
      approaches to improve these statistics. Methods include systems analysis,
      literature review, and the application of the Health Metrics Network (HMN) self
      assessment tool by key stakeholders. We identified two weaknesses underlying
      incompleteness of death registration and inaccuracy of COD attribution: problems
      in recording events or certifying deaths, and problems in transferring
      information from death certificates to death registers. Deaths occurring outside
      health facilities, representing 65% of all deaths in Thailand, contribute to the
      inaccuracy of cause-of-death data because they must be certified by village heads
      with limited knowledge and expertise in cause-of-death attribution. However,
      problems also exist with in-hospital cause-of-death certification by physicians.
      Priority should be given to training medical personnel in death certification,
      review of medical records by health personnel in district hospitals, and use of
      verbal autopsy techniques for assessing internal consistency. This should be
      coupled with stronger collaboration with district registrars for the 65% of
      deaths that occur outside hospitals. Training of physicians and data coders and
      harmonization of death certificates and registries would improve COD data for the
      35% of deaths that take place in hospital. Public awareness of the importance of
      registering all deaths and the application of registration requirements prior to
      funerals would also improve coverage, though enforcement would be difficult.

PMID- 16583084
TI  - Verbal autopsy: current practices and challenges.
AB  - Cause-of-death data derived from verbal autopsy (VA) are increasingly used for
      health planning, priority setting, monitoring and evaluation in countries with
      incomplete or no vital registration systems. In some regions of the world it is
      the only method available to obtain estimates on the distribution of causes of
      death. Currently, the VA method is routinely used at over 35 sites, mainly in
      Africa and Asia. In this paper, we present an overview of the VA process and the
      results of a review of VA tools and operating procedures used at demographic
      surveillance sites and sample vital registration systems. We asked for
      information from 36 field sites about field-operating procedures and reviewed 18
      verbal autopsy questionnaires and 10 cause-of-death lists used in 13 countries.
      The format and content of VA questionnaires, field-operating procedures, cause-of
      death lists and the procedures to derive causes of death from VA process varied
      substantially among sites. We discuss the consequences of using varied methods
      and conclude that the VA tools and procedures must be standardized and reliable
      in order to make accurate national and international comparisons of VA data. We
      also highlight further steps needed in the development of a standard VA process.

PMID- 16583085
TI  - Assessing probable causes of death without death registration or certificates: a
      new science?

PMID- 16583086
TI  - Assessing probable causes of death using a standardized questionnaire: a study in
      rural Senegal.

PMID- 16583087
TI  - Capturing health information -- a coding perspective.

PMID- 16583088
TI  - Counting the dead and what they died of.

PMID- 16583090
TI  - The Brazilian Ministry of Health and science, technology, and innovation policy.

PMID- 16583091
TI  - [HIV-1 diversity: a tool for studying the pandemic].
AB  - HIV-1 is remarkable for the diversity of strains comprising the HIV/AIDS
      pandemic. In the last decade, classification of viral variants as groups,
      subtypes, and circulating recombinant forms (CRF) and the observation of specific
      mutational patterns have become powerful tools for studying viral molecular
      dynamics. Monitoring the worldwide distribution of HIV-1 diversity has been used
      in both epidemiological surveillance programs and in reconstructing the history
      of regional epidemics. Specific patterns of virus spatial distribution also
      suggest differences in pathogenicity and transmissibility among the various
      subtypes. Molecular analyses of viral sequences allow estimating the rate of
      divergence among variants and the dynamic forces shaping the phylogenetic trees.

PMID- 16583092
TI  - Occupational exposure and effects on the male reproductive system.
AB  - A significant increase in the incidence of male infertility has been described in
      the international literature, raising questions about its causes. Part of this
      effect may result from synthetic toxic substances acting on the endocrine system
      (endocrine disruptors), many of which are routinely used in work processes. We
      provide a critical review of the specialized literature on work-related chemical
      substances capable of causing male infertility. Pesticides such as DDT, linuron,
      and others, heavy metals like mercury, lead, cadmium, and copper, and substances
      from various industrial uses and residues such as dioxins, polychlorinated
      biphenyls (PCBs), ethylene dibromide (EDB), phthalates, polyvinyl chloride (PVC),
      and ethanol are among the main endocrine disruptors that can cause male
      infertility. Based on the literature, gonadal dysfunction and congenital
      malformation are the main alterations caused by these substances in the male
      reproductive system. We conclude that despite the relative lack of studies on
      this issue, the relevance of such risk calls for further studies as well as
      measures to prevent workers' exposure to the various substances.

PMID- 16583093
TI  - [Characterization of Rickettsia spp. circulating in a silent peri-urban focus for
      Brazilian spotted fever in Caratinga, Minas Gerais, Brazil].
AB  - The present study was intended to characterize Rickettsia spp. circulating in
      arthropod vectors in Caratinga, Minas Gerais, Brazil, by PCR and to investigate
      the presence of antibodies against the spotted fever Rickettsiae group (SFRG) in
      dogs and horses. 2,610 arthropods were collected and taxonomically identified.
      DNA samples obtained from these vectors were submitted to PCR and cycle
      sequenced. Ctenocephalides and Amblyomma cajennense showed sequences presenting
      100.0% homology with R. felis. A sequence obtained from Rhipicephalus sanguineus
      showed 99.0% homology with R. felis, and a sequence from A. cajennense showed
      97.0% homology with R. honei and R. rickettsii. Canine (73) and equine (18) serum
      samples were tested by indirect fluorescent antibody (IFA) using R. rickettsii
      antigen. Only three of the equine sera tested (17.0%) had positive antibody
      titers. Molecular detection of rickettsiae species potentially pathogenic to
      humans in arthropod vectors and the presence of seroreactivity to SFRG in horses
      show the risk of transmission of rickettsiosis in this area and the need to
      maintain continuous epidemiological surveillance for rickettsial diseases.

PMID- 16583094
TI  - Psychometric properties of the Portuguese version of the Conflict Tactics Scales:
      Parent-child Version (CTSPC) used to identify child abuse.
AB  - This article follows another, which presented the first phase of the cross
      cultural adaptation process examining the psychometric properties of the Conflict
      Tactics Scales, Parent-child Version (CTSPC), Portuguese version. Fieldwork took
      place in three public maternity wards in Rio de Janeiro, Brazil, from March to
      September 2000. Interviews relate to siblings of randomly selected live births.
      Respondents were mothers. Information on partners was obtained by proxy. Almost
      all intra-observer reliability kappa estimates were above 0.75. Depending on the
      scale and type of perpetrator, internal consistency (a) estimates ranged from
      0.49 to 0.68. Using the same sample, the iterated principal factor analysis
      identified four dimensions. Although most items performed well, some failed to
      adequately load in their expected factors. Construct validity involved exploring
      the relationship between several other theoretical dimensions and a variable
      encompassing the cumulative pattern of violence severity. All the hypotheses
      tested were corroborated. The current evaluation indicates that the CTSPC can be
      recommended for use in Portuguese-speaking contexts. Still, it also identified
      some important points needing further investigation and discussion.

PMID- 16583095
TI  - [Use of remote sensing to study the influence of environmental changes on malaria
      distribution in the Brazilian Amazon].
AB  - Construction of the Tucurui hydroelectric dam in Southeast Para State, Brazil, in
      1981, caused enormous environmental changes, deforestation, and human migration
      to the region. This study focuses on the influence of these changes and the
      appearance of malaria in the municipality of Jacunda, Para, using remote sensing
      and geographic information systems. The variables used to construct maps were
      distances from roads, farming areas, rivers, the dam, streams, and the urban
      area. This study confirmed the elevation of malaria to the epidemic level since
      the construction of the Tucurui dam. The study suggests that a seasonal pattern
      of malaria incidence is associated with the flooding season and exposure of
      workers during harvest. Malaria cases were related to the form of land
      occupation, especially in more densely populated areas.

PMID- 16583096
TI  - [Caregivers of elderly with advanced cancer: vulnerable actors].
AB  - Cancer presents high prevalence and mortality rates among elderly Brazilians, and
      family members provide meaningful care, especially during terminal illness. A
      literature review focused on the impact for families and the physical,
      psychological, social, and economic burden for family caregivers of seniors with
      advanced cancer, as well as related interventions. More studies are needed on
      family caregivers of elderly with advanced cancer in Brazil in order to develop
      programs to protect these important social actors.

PMID- 16583097
TI  - Validity and reliability of the Baecke questionnaire for the evaluation of
      habitual physical activity among people living with HIV/AIDS.
AB  - This study evaluates the validity and reliability of the Baecke questionnaire on
      habitual physical activity when applied to a population of HIV/AIDS subjects.
      Validity was determined by comparing measurements for 30 subjects of peak oxygen
      uptake, peak workload, and energy expenditure with scores for occupational
      physical activity (OPA), physical exercise in leisure (PEL), leisure and
      locomotion activities (LLA), and total score (TS). Reliability was determined by
      testing and retesting 29 subjects at intervals of 15-30 days. Validity was
      evaluated with the Pearson correlation and reliability analyses were done using
      the intraclass correlation, paired Student t-test, and Bland-Altman methods. Peak
      VO2 and peak workload had significant correlation with PEL (r = 0.41; r = 0.43;
      respectively). Energy expenditure had a significant correlation with OPA (r =
      0.64). The intraclass coefficients were 0.70 or more for OPA, PEL and TS. There
      was no difference in OPA, PEL, LLA and TS between the two evaluations. The Bland
      Altman methods showed that there was good agreement between the measurements for
      all habitual physical activities scores. Results show that the Baecke
      questionnaire is valid for the evaluation of habitual physical activity among
      people living with HIV/AIDS.

PMID- 16583098
TI  - [Occupational status and cancer of the oral cavity and oropharynx].
AB  - To estimate the risk of occupation in oral and oropharyngeal cancer, a hospital
      based case-control study was conducted in Greater Metropolitan Sao Paulo, Brazil.
      The study included 325 cases and 468 controls, frequency-matched with cases by
      sex and age, and interviewed from January 1999 to March 2002. Occupational risks
      were examined by industry and job titles and restricted to males (266 cases, 362
      controls). Odds ratios (OR) were calculated by unconditional logistic regression,
      controlling for age, smoking, and alcohol. Males working in vehicle maintenance
      shops (26 cases, 12 controls) showed adjusted OR = 2.45 (95%CI: 1.14-5.27),
      increasing among those employed 10 or more years (OR = 7.90; 95%CI: 2.03-30.72).
      Occupation as vehicle repair worker (14 cases, 7 controls) showed OR = 2.10
      (95%CI: 0.78-5.68), increasing among workers exposed 10 or more years (OR =
      26.21; 95%CI: 2.34-294.06). Other industries and occupations revealed OR higher
      than 1.5, but not statistically significant. In conclusion, employment in vehicle
      maintenance shops and occupation as vehicle repair worker showed risk for oral
      cancer, independently of smoking and alcohol. More prolonged exposure increased
      the risk.

PMID- 16583099
TI  - [Evaluation of antenatal peregrination in a sample of postpartum women in Rio de
      Janeiro, Brazil, 1999/2001].
AB  - The access to obstetric care in the city of Rio de Janeiro, Brazil, was evaluated
      in this study. The aim of this article was to determine the social, demographic
      and obstetric factors associated with the antenatal search for health services,
      in a sample of 6,652 postpartum women. It was observed that 1/3 of patients have
      to search for services in more than one hospital, not uncommonly in 3 or more. It
      is important to consider that only 1/5 of these patients are transferred by
      ambulance. The factors associated with this peregrination were: place of
      residence, birth weight, age, skin color, marital status and residence in places
      where garbage is not picked up. There was no association with schooling;
      Kotelchuck modified index, obstetric risk, water source and residence in slums.

PMID- 16583100
TI  - [Implementation of World Health Organization guidelines for management of severe
      malnutrition in a hospital in Northeast Brazil].
AB  - To assess the implementation of WHO guidelines for managing severely malnourished
      hospitalized children, a case-series study was performed with 117 children from 1
      to 60 months of age. A checklist was prepared according to steps in the
      guidelines and applied to each patient at discharge, thus assessing the
      procedures adopted during hospitalization. Daily spreadsheets on food and liquid
      intake, clinical data, prescribed treatment, and laboratory results were also
      used. 36 steps were evaluated, 24 of which were followed correctly in more than
      80% of cases; the proportion was 50 to 80% for seven steps and less than 50% for
      five steps. Monitoring that required frequent physician and nursing staff bedside
      presence was associated with difficulties. With some minor adjustments, the
      guidelines can be followed without great difficulty and without compromising the
      more important objective of reducing case-fatality.

PMID- 16583101
TI  - PCR in the investigation of canine American tegumentary leishmaniasis in
      northwestern Parana State, Brazil.
AB  - American tegumentary leishmaniasis (ATL) was studied in 143 dogs in a rural area
      in the county of Mariluz, northwestern Parana State, Brazil, using direct
      parasite search, indirect immunofluorescence (IIF), and polymerase chain reaction
      (PCR). Thirty-nine dogs (27.3%) presented lesions suggestive of the disease, 5
      (12.8%) of which were positive in direct parasite search and PCR (lesion), and of
      these 5, 4 were also positive by IIF. Of the 34 dogs with negative direct
      parasite search, 12 (35.3%) had PCR-positive lesions, and of these, 5 were also
      IIF-positive. One hundred and four dogs had no lesions, but 17/101 (16.8%) were
      IIF-positive. PCR in blood was positive in 10/38 (26.3%) of the dogs with lesions
      and in 16/104 (15.4%) of dogs without lesions. The association between PCR
      (lesion or blood), direct parasite search, and IIF detected 24/39 (61.5%)
      positive results among symptomatic dogs and 31/104 (29.8%) among asymptomatic
      animals. PCR was useful for diagnosing ATL, but there was no correlation between
      lesions, serology, and plasma PCR. Furthermore, detection of parasite DNA in the
      blood may indicate hematogenous parasite dissemination.

PMID- 16583102
TI  - [Household smoking and respiratory disease in under-five children].
AB  - Environmental tobacco smoke is an important respiratory tract irritant in young
      children. To identify factors associated with respiratory disease and determine
      the main source of smoking exposure in the household, a cross-sectional study of
      2,037 children who were immunized in primary health care clinics was conducted
      (in a sample of 10 out of 38 clinics with 200 children each). Parents answered a
      questionnaire about children's birth, passive smoking, former and current
      respiratory morbidity, socio-demographic characteristics, and living conditions.
      Analysis was based on hierarchical logistic regression. Prevalence of respiratory
      symptoms was 59.9% for children who live with smokers. Asthma and bronchitis
      showed the strongest association with smoking. In multivariate logistic
      regression, the following variables remained associated with asthma/bronchitis:
      socioeconomic status (OR = 2.93; 95%CI: 1.57-5.45), maternal schooling (OR =
      1.46; 95%CI: 1.08-1.98)] and occupation (OR = 1.68; 95%CI: 1.04-2.74),
      neighborhood (OR = 1.47; 95%CI: 1.06-2.02), child's age (OR = 3.38; 95%CI: 2.31
      4.95) and sex (OR = 1.46; 95%CI: 1.09-1.94), breastfeeding (OR = 1.66; 95%CI:
      1.15-2.40), and household smoking (OR = 1.58; 95%CI: 1.18-2.11). Children with
      lower socioeconomic status and exposed to household smoking showed increased risk
      of respiratory disease.

PMID- 16583103
TI  - [Profile of poisonings among Brazilian adolescents from 1999 to 2001].
AB  - This paper analyzes the profile of poisonings among adolescents as reported by
      the Brazilian National Poisoning Information System (SINITOX) database. This
      database covers cases and deaths secondary to human poisoning recorded by Poison
      Control Centers (1999-2001). With relation to cases, venomous animals (33.7%) and
      medicines (25.7%) are the main toxic agents in pre-adolescents (10-14 years). For
      adolescents (15-19 years), medicines ranked first (33.0%), followed by
      bites/stings from venomous animals (21.4%). There were 35 deaths among pre
      adolescents, 54.3% resulting from accidental poisoning, 54.3% in males, and 31.4%
      caused by venomous animals. Ninety-eight deaths were reported among adolescents,
      72.4% of which were suicides, 54.1% in females, and 38.8% resulting from
      pesticide poisoning.

PMID- 16583104
TI  - [Kangaroo Mother Care in public hospitals in the State of Sao Paulo, Brazil: an
      analysis of the implementation process].
AB  - This study analyzed the implementation of the Kangaroo Mother method in 28
      different Sao Paulo State public hospitals. Teaching hospitals, Baby-Friendly
      Hospitals, hospitals with human milk banks, and those with more than 12 trained
      health professionals showed higher implementation scores. Because of staff
      resistance to family participation in neonatal care, the Kangaroo Mother method
      is basically applied in-hospital. Changes in the initial training, including
      manager awareness-raising and proper financial resource allocation, are necessary
      for implementation, follow-up, assessment, and feedback.

PMID- 16583106
TI  - [Disclosure of HIV infection from the perspective of adolescents living with
      HIV/AIDS and their parents and caregivers].
AB  - The purpose of this study was to identify relevant issues in the disclosure of
      HIV-positive status in children and adolescents, aiming to improve the quality of
      their healthcare. A qualitative study included adolescents living with HIV/ AIDS
      and their parents and caregivers at AIDS reference services in Sao Paulo and
      Santos, Brazil. In-depth interviews and focus group were used. The main reasons
      for disclosure were: poor treatment adherence, sexual maturity, adolescent's
      request, and inadequate procedures by medical staff. Disclosure was a critical
      moment for adolescents, with a strong impact on their life plans and horizons.
      Adolescents infected through sexual transmission and drug use reported the most
      problematic scenes involved in disclosure. Despite its initial negative impact,
      disclosure resulted in improved healthcare and better dialogue among the
      adolescents, caregivers, and healthcare providers. The adolescents also requested
      clear, no-nonsense, honest information. The authors conclude that health services
      need to actively provide an adequate approach to facilitate disclosure of HIV
      positive status to children and adolescents, realizing that it is a long-term
      process supported by the family and a multidisciplinary team.

PMID- 16583105
TI  - [Program for hearing loss prevention in four metallurgical factories in
      Piracicaba, Sao Paulo, Brazil].
AB  - This study analyzes noise control programs in four metallurgical factories in
      Piracicaba, Sao Paulo, Brazil. From 1997 to 2001, 741 workers were examined and
      the programs were analyzed based on workers' profiles (2,270 audiometric exams)
      and documents on hearing preservation programs. 41% of workers presented hearing
      loss (mean age 42.3; mean years of work 16.7). 104 workers with more than one
      audiometric exam presented changes in hearing threshold. 36.5% (38 workers)
      developed noise-induced hearing loss (NIHL) and 63.5% (66 workers) with existing
      NIHL showed worsening of their hearing threshold. In these factories, 69.5% of
      workers were exposed to > or = 84dB(A). We concluded that the hearing
      preservation programs are not adequately organized and that workers are still
      exposed to high noise levels at work, posing a risk for NIHL. In addition, the
      current legislation on hearing loss prevention is not enforced.

PMID- 16583107
TI  - [Participatory planning in health organizations: the case of the Bonsucesso
      General Hospital, Rio de Janeiro, Brazil].
AB  - This article presents the experience with participatory planning in the
      Bonsucesso General Hospital in Rio de Janeiro, Brazil, from 2003 to 2004. The
      participatory and communicative characteristics and the resulting institutional
      format are identified for guaranteeing the implementation of collective decisions
      from the planning workshops. The limits of implementation in participatory
      planning and management proposals are argued from the perspective of change and
      power relations in these institutions. The results support the notion that
      projects involving changes in hospitals and failing to take into account the
      different internal rationalities and power relations end up having reduced
      potential for implementation.

PMID- 16583108
TI  - [Validation of birth certificates based on data from a case-control study].
AB  - The information recorded on birth certificates was validated with data from a
      perinatal mortality case-control study, obtained from home interviews of mothers
      and hospital records for cases (early neonatal deaths) and controls. Sensitivity,
      specificity, and concordance were calculated for all variables and their
      estimated and real prevalence. The completeness of birth certificates was lowest
      for mother's parity and presence of congenital anomalies (records without
      information range from 23% to 31% for cases and controls). Birth certificates
      correctly identified low birth weight and type of delivery for cases and
      controls. Birth certificates showed high sensitivity and specificity to detect
      preterm births within cases. The number of preterm births was underestimated at
      30.8% of the controls and 2.9% of the cases. Low maternal education was two times
      greater on birth certificates than in the mother's interview, for cases and
      controls. Completeness of birth certificates was higher in controls, but data
      quality was better in cases.

PMID- 16583109
TI  - [Social representations of generic drugs by consumers from Natal, Rio Grande do
      Norte, Brazil].
AB  - This paper aimed to determine the central and peripheral roles of consumers'
      social representations concerning generic drugs, establishing mechanisms that
      could be used to improve policies for this type of medication in Brazil. The
      research was done from April 2002 to February 2003 in the city of Natal, Rio
      Grande do Norte, with 400 consumers. The study employed the word association test
      with the words "generic drug" as the inductive stimulus. Evocation of three words
      was requested, according to the access strategy to Verges' Central Nucleus. Data
      analysis used the EVOC 2000 software and the content analysis proposed by Bardin.
      The results demonstrated that the central nucleus consisted of the categories
      price, quality, and pharmaceutical equivalence, while the peripheral system was
      represented by the categories option, effectiveness, government, social benefit,
      and accessibility.

PMID- 16583110
TI  - [Use of psychoactive drugs by health sciences undergraduate students at the
      Federal University in Amazonas, Brazil].
AB  - A survey was conducted with 521 undergraduate health sciences students from the
      Federal University in Amazonas, Manaus, Brazil. Lifetime alcohol consumption was
      reported by 87.7% students, as compared to 30.7% for tobacco, with the latter
      reported more frequently by males (39.7%). The most common illicit drugs were
      solvents (11.9%), marijuana (9.4%), amphetamines and anxiolytics (9.2% each),
      cocaine (2.1%), and hallucinogens (1.2%). The main reason for illicit drug use
      was curiosity. Lifetime use of anabolic steroids was reported by 2.1% of the
      students. Alcohol abuse in the previous 30 days was reported by 12.4% of the
      students. Events following drinking included: fights (4.7%), accidents (2.4%),
      classroom absenteeism (33.7%), and job absenteeism (11.8%). Another important
      finding was that 47.3% of students drove after drinking. Opinions on drug abuse
      and patterns agree with those from similar studies in other regions of Brazil.

PMID- 16583111
TI  - [Quality of socioeconomic and demographic data in relation to infant mortality in
      the Brazilian Mortality Information System (1996/2001)].
AB  - This study aimed to evaluate the quality of socioeconomic and demographic data in
      the Brazilian Mortality Information System (SIM), in relation to infant
      mortality. The article assesses the system's potential for monitoring
      inequalities in infant mortality in various States in the country. Accessibility,
      timeliness, methodological clarity, incompleteness, and consistency were explored
      as quality indicators. Selected variables were: race, birth weight, gestational
      age, medical care, parity, and maternal schooling, age, and occupation. The study
      also reviewed the system's working documentation and the scientific literature on
      infant mortality. Proportions of data incompleteness were calculated by region
      and State, identifying factors that might influence (in)completeness using
      logistic regression. Despite the database's accessibility and the relevance of
      most of its variables, the system has serious quality problems: confusing
      instructions in the information manual concerning missing data, misclassification
      of maternal occupation, lack of data on the informant's race/ethnicity, and high
      proportions of incomplete information. The system does not appear to be a
      reliable source for monitoring, evaluating, and planning measures to minimize
      infant health inequalities.

PMID- 16583112
TI  - [Prevention of mental retardation: knowledge and perception by health
      professionals].
AB  - This article aimed to evaluate the prevention of mental disability in primary
      healthcare services in Maringa, Parana, Brazil. The sample consisted of 90 male
      and female physicians from different fields, namely gynecology and obstetrics,
      pediatrics, general practice, and family health, as well as 66 male and female
      nurses. A multiple-choice questionnaire was filled out by the subjects themselves
      from August to December 2003. Qualitative variables were compared using the chi
      square test at 5% significance level. Partial data relating to both the
      perception and knowledge of health professionals concerning mental disability
      were as follows: 75% were unable to choose the correct alternative on prevalence;
      25% did not know how the genome contributes to etiology; 37% were unaware of
      prevention for mental disability; 28% were not confident in providing orientation
      on the teratogenic effect of ethanol; 35% demonstrated insecurity in orienting
      patients on amniocentesis. The data showed that participants had an
      unsatisfactory perception of the relevance of mental disability within the
      overall population disease profile, and that they need more information on the
      respective genetic and environmental issues.

PMID- 16583113
TI  - Relation between rates of geriatric suicide and consumption of alcohol beverages
      in European countries.
AB  - Among older adults, suicide is a significant and persistent health problem. The
      highest suicide rate is found among white men aged 65 years and older. The causes
      of elder suicide are multifaceted. Although no predominate factor precipitates or
      explains geriatric suicide, alcohol is strongly linked to suicide attempts and
      completions. This study examined the relationship between rates of suicide in 65-
      to 74-year-olds and per capita consumption of alcoholic beverages in European
      countries. Data on suicide rates in 65- to 74-year-olds and per capita
      consumption of alcoholic beverages were obtained from the World Health
      Organization databases. Correlations were computed to examine relationships
      between suicide rates in 65- to 74-year-old males and females and per capita
      consumption of beer, wine, and spirits in the general population in 34 European
      countries. There was a positive correlation between suicide rates in 65- to 74
      year-old males and per capita consumption of spirits. No correlations between
      suicide rates in 65- to 74-year-old males and per capita consumption of beer or
      wine were found. We also found no correlations between rates of suicide in 65- to
      74-year-old females and per capita consumption of beer, wine, or spirits. The
      results of this study are consistent with reports that consumption of spirits is
      associated with suicide events. It is to be hoped that this paper will stimulate
      further studies that are necessary to clarify the relation between suicide rates
      in different age groups and consumption of alcoholic beverages, and attract more
      attention to the problem of geriatric suicide.

PMID- 16583114
TI  - Development of a positive youth development program: helping parents to improve
      their parenting skills.
AB  - The Project PATHS (Positive Adolescent Training through Holistic Social Programs)
      is a positive youth development program that attempts to promote holistic
      development in adolescents in Hong Kong. In the Tier 2 Program of this project,
      social workers are expected to develop positive youth development programs for
      adolescents having greater psychosocial needs. They are required to submit
      proposals that will be evaluated in terms of whether the proposals are evidence
      based, and appropriate evaluation mechanisms are included. With reference to the
      literature on parental control processes that Chinese parents may be loose in
      their behavioral control and they tend to overemphasize academic excellence, it
      is argued that improvement of the parenting skills of parents of Chinese
      adolescents is an important area to be addressed. To facilitate social workers to
      prepare the related proposals, a sample proposal on how to improve the parenting
      skills of Chinese parents is described, including its conceptual framework,
      proposed program, and evaluation plan. It is argued that this supportive approach
      (i.e., preparation of a sample proposal) can help social workers to develop
      quality proposals on positive youth development programs in Hong Kong.

PMID- 16583115
TI  - Development of a positive youth development program: promoting the mental health
      of stressful adolescents using principles of Problem Solving Therapy.
AB  - This paper outlines the proposal for the development, implementation, and
      evaluation of a positive youth development program that attempts to promote the
      mental health of stressful Chinese adolescents using principles of Problem
      Solving Therapy (PST). There are two general aims of PST: to help clients
      identify life difficulties and resolve them, as well as to teach them skills on
      how to deal with future problems. The proposed project will utilize the
      principles of PST as the guiding framework to run two mental health promotion
      courses for adolescents who are experiencing disturbing stressful responses and
      students who want to improve their stress management style. Both objective and
      subjective outcome evaluation strategies will be carried out to assess the
      effectiveness of the intervention to promote the psychological well-being in
      adolescents who are experiencing stress. A related sample proposal is described
      that can give social workers some insight on how to prepare a proposal for
      developing the Tier 2 Program of the Project PATHS (Positive Adolescent Training
      through Holistic Social Programs).

PMID- 16583116
TI  - The two thrombospondin type I repeat domains of HB-GAM display a cooperative
      function in N-syndecan binding and regulation of synaptic plasticity.

PMID- 16583117
TI  - The forgotten stent: late complication in a patient with neobladder.
AB  - Encrustation constitutes a serious complication of ureteral stent use and can
      result in difficult stent removal. We report the case of a patient with a
      retained ureteral stent for 3 years following a radical cystectomy.

PMID- 16583122
TI  - Reply to letter by Dionne.

PMID- 16583124
TI  - Co-existing symptoms and risk factors among African school children with
      hyperactivity-inattention symptoms in Kinshasa, Congo.
AB  - The aims of the study were to explore hyperactivity-inattention (HI) symptoms and
      co-existing symptoms of emotional and behavioural problems among African school
      children and their relationship with health status, socio-demographic factors,
      and school performance. METHOD: A case-control approach was used. The Strengths
      and Difficulties Questionnaire (SDQ) was used to explore the co-existing
      emotional and behavioural symptoms and a semi-structured interview with parents
      to explore the socio-demographic variables. The sample included 357 school
      children at the age of 7-9 years: 183 children were defined as cases, defined by
      abnormal scores on the SDQ-HI scale and 174 randomly selected children among
      those with normal scores on the SDQ-HI were defined as controls. No age and
      gender differences were noticed between the two groups. RESULTS: A younger
      maternal age at childbirth, and poor school performances were more frequent among
      cases than controls. Three quarter of the hyperactive-inattentive children had co
      existing symptoms according to SDQ, the most common being conduct problems.
      CONCLUSION: As in other cultures, co-existence of HI symptoms and emotional and
      behavioural problems was found in this African setting. Further validation of
      behavioural screening instruments in African children is called for.

PMID- 16583125
TI  - PRN sedation-patterns of prescribing and administration in a child and adolescent
      mental health inpatient service.
AB  - OBJECTIVE: To identify utilisation rates of prn (pro re nata) sedation in
      children and adolescents receiving inpatient psychiatric treatment, and to
      compare correlates of prn prescribing and administration. METHOD: A retrospective
      chart review examined 122 medical charts from a child and youth mental health
      inpatient service. RESULTS: 71.3% of patients were prescribed prn sedation and
      50.8% were administered prn sedation. Patients received an average of 8.0 doses
      of prn sedation, with 9.8% receiving 10 or more doses. Chlorpromazine and
      diazepam were the most commonly utilised agents. Prescribing of prn sedation was
      only related to use of regular medications (p < 0.01), and non-parent carers (p <
      0.01). In contrast, administration of prn sedation was associated with multiple
      diagnoses (p < 0.01), pervasive development disorder (p < 0.01), mental
      retardation (p < 0.01) ADHD (p < 0.01), longer hospital admission (p < 0.01), use
      of atypical antipsychotics (p < 0.01) and polypharmacy (p < 0.01). CONCLUSIONS:
      Despite lack of data to inform practice, prn sedation is widely utilised,
      especially in complex patients. Future research in this area needs to incorporate
      nurses and examine whether patients benefit from prn sedation, which drugs and
      dosing patterns optimise safety and efficacy, and what is the role of prn
      sedation in the context of other medication.

PMID- 16583126
TI  - Therapeutic effects of gelatin-resorcin-formal glue in the treatment of
      postoperative fistula following a low anterior resection: report of a case.
AB  - Postoperative fistulas are among the most difficult and distressing of surgical
      problems. We describe a case of a discharging fistula that developed after low
      anterior resection and was successfully treated with a new biologic adhesive
      agent, gelatin-resorcin-formal glue. To our knowledge, this is the first reported
      case of a postoperative fistula after colorectal surgery successfully treated
      with gelatin-resorcin-formal glue. In conclusion, gelatin-resorcin-formal glue is
      useful for uncontrollable postoperative fistula.

PMID- 16583127
TI  - A novel missense mutation of the EDA gene in a Mongolian family with congenital
      hypodontia.
AB  - X-linked hypohidrotic ectodermal dysplasia (HED) is a rare disease characterized
      by the hypoplasia or absence of eccrine glands, dry skin, scant hair, and dental
      abnormalities. Here, we report a Mongolian family with congenital absence of
      teeth inherited in an X-linked fashion. The affected members of the family did
      not show other HED characteristics, except hypodontia. We successfully mapped the
      affected locus to chromosome Xq12-q13.1, and then found a novel missense
      mutation, c.193C>G, in the ectodysplasin A (EDA) gene in all affected males and
      carrier females. The mutation causes arginine to be replaced by glycine in codon
      65 (R65G) in the juxtamembrane region of EDA. In addition, 33% (3/9) of female
      carriers have a skewed X-chromosome inactivation pattern. Our result strongly
      suggests that the c.193C>G mutation is the disease-causing mutation in this
      family.

PMID- 16583128
TI  - Sequence polymorphisms of the mtDNA control region in a human isolate: the
      Georgians from Swanetia.
AB  - In this work, we analyzed the sequence diversity of the mtDNA control region (HVI
      and HVII) in a sample of 48 individuals from Swanetia (Georgia), using direct
      fluorescent-based sequencing methods. We identified 43 different mtDNA haplotypes
      resulting from 78 polymorphic sites (46 in HVI and 32 in HVII). Most of the
      variable positions identified in both HVI and HVII were transitions (82.6 and
      71.9%, respectively). The frequency of length heteroplasmy in the homopolymeric C
      stretch regions was the same for both segments (10.4%). The sequence diversity
      increased markedly when both hypervariable regions were analyzed jointly (HVI:
      0.985, HVII: 0.975, HVI+HVII: 0.994). Accordingly, the probability of two
      randomly selected sequences matching (random match probability, RMP) decreased
      from 3.4% (HVI) to 2.6% (HVI+HVII), despite which the RMP values in Georgians
      remained higher than estimated in most Europeans. This suggests that the
      variability of maternal lineages tends to be lower in traditional human isolates
      and, therefore, the potential of discrimination of mtDNA in forensic analysis is
      more limited in this type of population. The incorporation of HVII data also
      contributed to the refinement of results regarding the genetic relationships
      among the samples included in the analyses, which stress the importance of
      considering HVII in both population and forensic genetics.

PMID- 16583129
TI  - Diagnosis and cell-based therapy for Duchenne muscular dystrophy in humans, mice,
      and zebrafish.
AB  - The muscular dystrophies are a heterogeneous group of genetically caused muscle
      degenerative disorders. The Kunkel laboratory has had a longstanding research
      program into the pathogenesis and treatment of these diseases. Starting with our
      identification of dystrophin as the defective protein in Duchenne muscular
      dystrophy (DMD), we have continued our work on normal dystrophin function and how
      it is altered in muscular dystrophy. Our work has led to the identification of
      the defective genes in three forms of limb girdle muscular dystrophy (LGMD) and a
      better understanding of how muscle degenerates in many of the different
      dystrophies. The identification of mutations causing human forms of dystrophy has
      lead to improved diagnosis for patients with the disease. We are continuing to
      improve the molecular diagnosis of the dystrophies and have developed a high
      throughput sequencing approach for the low-cost rapid diagnosis of all known
      forms of dystrophy. In addition, we are continuing to work on therapies using
      available animal models. Currently, there are a number of mouse models of the
      human dystrophies, the most notable being the mdx mouse with dystrophin
      deficiency. These mice are being used to test possible therapies, including stem
      cell-based approaches. We have been able to systemically deliver human dystrophin
      to these mice via the arterial circulation and convert 8% of dystrophin-deficient
      fibers to fibers expressing human dystrophin. We are now expanding our research
      to identify new forms of LGMD by analyzing zebrafish models of muscular
      dystrophy. Currently, we have 14 different zebrafish mutants exhibiting various
      phenotypes of muscular dystrophy, including muscle weakness and inactivity. One
      of these mutants carries a stop codon mutation in dystrophin, and we have
      recently identified another carrying a mutation in titin. We are currently
      positionally cloning the disease-causative mutation in the remaining 12 mutant
      strains. We hope that one of these new mutant strains of fish will have a
      mutation in a gene not previously implicated in human muscular dystrophy. This
      gene would become a candidate gene to be analyzed in patients which do not carry
      a mutation in any of the known dystrophy-associated genes. By studying both
      disease pathology and investigating potential therapies, we hope to make a
      positive difference in the lives of people living with muscular dystrophy.

PMID- 16583130
TI  - Resonance energy transfer in new fullerene-coumarin diads.
AB  - The fluorescence properties of new [60] and [70] fullerene-coumarin diads are
      studied. These diads were synthesized by covalently linking a coumarin dye to a
      fullerene (C60 or C70) by a cyclopropanation reaction. The absorption and
      fluorescence spectra, quantum yields and lifetimes of the diads are reported. The
      fluorescence quenching of the coumarin moiety by the fullerene was observed in
      all diads, indicating the occurrence of resonance energy transfer between the
      coumarin and fullerene moieties.

PMID- 16583131
TI  - Cumene peroxide and Fe(2+)-ascorbate-induced lipid peroxidation and effect of
      phosphoglucose isomerase.
AB  - Malondialdehyde (MDA) is one of cytotoxic aldehydes produced in cells as a result
      of lipid peroxidation and further MDA metabolism in cytoplasm is not known. In
      our experiments the liver fraction 10,000 g containing phosphoglucose isomerase
      and enzymes of the glyoxalase system was used and obtained experimental data
      shows that in this fraction there is an aggregate of reactions taking place both
      in membranes (lipid peroxidation) and outside membranes. MDA accumulation is
      relatively slow because MDA is a substrate of aldehyde isomerase (MDA <-->
      methylglyoxal). The well known enzyme phosphoglucose isomerase acts as an
      aldehyde isomerase (Michaelis constant for this enzyme Km = 133 +/- 8 microM).
      MDA conversion to methylglyoxal and further to neutral product D-lactate (with
      GSH as a cofactor) occurs in cytoplasm and D-lactate should be regarded as the
      end product of two different parametabolic reactions: lipid peroxidation or
      protein glycation.

PMID- 16583132
TI  - Effect of different oral doses of isoniazid-rifampicin in rats.
AB  - Hepatotoxicity is one of the most serious adverse effects of antituberculosis
      drugs. The aim of this study was to produce a rat model of isoniazid-rifampicin
      (INH-RIF) induced hepatotoxicity. MATERIALS AND METHODS: Wistar rats (100-150 g)
      were treated with different doses of INH i.e. 25, 50 and 75 mg/kg/day with a
      fixed dose of RIF i.e. 50 mg/kg/day intragastrically for a period of 28 days.
      Serum glutamate oxaloacetate aminotransferase (SGOT), glutamate pyruvate
      aminotransferase (SGPT), bilirubin (Bil) and alkaline phosphatase (ALP) were
      estimated at 0,14, 21 and 28 days in rats. Histological analysis was carried out
      to assess the liver. RESULTS: Treatment of rats with INH-RIF (50 mg/kg/day each)
      induced hepatotoxicity as judged by elevated serum SGPT, SGOT, Bil and ALP as
      compared with their base line. Histological evaluation of INH-RIF induced
      hepatotoxicity also showed liver damage. CONCLUSION: The present study suggests
      that 50 mg/kg/day each of INH-RIF was selected as hepatotoxic dose (i.e. minimum
      dose with maximum hepatotoxicity) in wistar rats.

PMID- 16583133
TI  - Effects of carbenoxolone on heart rhythm, contractility and intracellular calcium
      in streptozotocin-induced diabetic rat.
AB  - Cardiac dysfunction is a frequently reported complication of clinical and
      experimental diabetes mellitus. Streptozotocin (STZ)-induced diabetes in rat is
      associated with a variety of cardiac defects including disturbances to heart
      rhythm and prolonged time-course of cardiac muscle contraction and/or relaxation.
      The effects of carbenoxolone (CBX), a selective gap junction inhibitor, on heart
      rhythm and contractility in STZ-induced diabetic rat have been investigated.
      Heart rate was significantly (P < 0.05) reduced in Langendorff perfused
      spontaneously beating diabetic rat heart (171+/-12 BPM) compared to age-matched
      controls (229+/- 9 BPM) and further reduced by 10(-5) M CBX in diabetic (20%) and
      in control (17%) hearts. Action potential durations (APDs), recorded on the
      epicardial surface of the left ventricle, were prolonged in paced (6 Hz) diabetic
      compared to control hearts. Perfusion of hearts with CBX caused further
      prolongation of APDs and to a greater extent in control compared to diabetic
      heart. Percentage prolongation at 70% from the peak of the action potential
      amplitude after CBX was 18% in diabetic compared to 48% in control heart. CBX had
      no significant effect on resting cell length or amplitude of ventricular myocyte
      shortening in diabetic or control rats. However, resting fura-2 ratio (indicator
      for intracellular Ca(2+) concentration) and amplitude of the Ca(2+) transient
      were significantly (P < 0.05) reduced by CBX in diabetic rats but not in
      controls. In conclusion the larger effects of CBX on APD in control ventricle and
      the normalizing effects of CBX on intracellular Ca(2+) in ventricular myocytes
      from diabetic rat suggest that there may be alterations in gap junction
      electrophysiology in STZ-induced diabetic rat heart.

PMID- 16583134
TI  - Enhanced beta-adrenergic receptors in the brain and pancreas during pancreatic
      regeneration in weanling rats.
AB  - Adrenergic stimulation has an important role in the pancreatic beta-cell
      proliferation and insulin secretion. In the present study, we have investigated
      how sympathetic system regulates the pancreatic regeneration by analyzing
      Epinephrine (EPI), Norepinephrine (NE) and beta-adrenergic receptor changes in
      the brain as well as in the pancreas. EPI and NE showed a significant decrease in
      the brain regions, pancreas and plasma at 72 hrs after partial pancreatectomy. We
      observed an increase in the circulating insulin levels at 72 hrs. Scatchard
      analysis using [(3)H] propranolol showed a significant increase in the number of
      both the low affinity and high affinity beta-adrenergic receptors in cerebral
      cortex and hypothalamus of partially pancreatectomised rats during peak DNA
      synthesis. The affinity of the receptors decreased significantly in the low and
      high affinity receptors of cerebral cortex and the high affinity hypothalamic
      receptors. In the brain stem, low affinity receptors were increased significantly
      during regeneration whereas there was no change in the high affinity receptors.
      The pancreatic beta-adrenergic receptors were also up regulated at 72 hrs after
      partial pancreatectomy. In vitro studies showed that beta-adrenergic receptors
      are positive regulators of islet cell proliferation and insulin secretion. Thus
      our results suggest that the beta-adrenergic receptors are functionally enhanced
      during pancreatic regeneration, which in turn increases pancreatic beta-cell
      proliferation and insulin secretion in weanling rats.

PMID- 16583136
TI  - The Spen homolog Msx2-interacting nuclear target protein interacts with the E2
      ubiquitin-conjugating enzyme UbcH8.
AB  - The nuclear matrix protein Msx2-interacting nuclear target protein (MINT) is a
      transcription factor that regulates the expression of key transcriptional
      effectors in diverse signaling pathways. To further understand the function and
      mechanism of the MINT-mediated transcription regulation, the yeast two-hybrid
      system was employed to screen proteins that interact with the C-terminal fragment
      of MINT. From a cDNA library of human lymph nodes, a cDNA encoding the ubiquitin
      conjugating enzyme UbcH8 was identified. Using different truncated versions of
      MINT, we show that the C-terminal Spen paralog and ortholog C-terminal domain
      (SPOC) domain, which has been demonstrated to mediate interactions between MINT
      and a panel of other molecules, might be responsible for interaction between MINT
      and UbcH8 in yeast, as confirmed by the beta-galactosidase assay. The interaction
      between MINT and UbcH8 in mammalian cells was further proved by a series of
      biochemical assays including the mammalian two-hybrid assay, GST pull-down assay,
      and co-immunoprecipitation assay. Using a reporter system, we found that MINT
      mediated transcription suppression was sensitive to MG132, an inhibitor of the
      proteosome system. These results suggest a novel mechanism of MINT-mediated
      transcription regulation, and might be helpful for understanding functions of
      MINT.

PMID- 16583135
TI  - On cell signalling mechanism of Mycobacterium leprae soluble antigen (MLSA) in
      Jurkat T cells.
AB  - We investigated the role of Mycobaterium leprae soluble antigen (MLSA) in the
      modulation of calcium signalling, phosphorylation of mitogen-activated protein
      (MAP) kinases and IL-2 mRNA expression in human Jurkat T cells. We observed that
      MLSA induced an increase in free intracellular calcium concentrations, [Ca2+]i,
      via opening CRAC (Ca2+-release activated- Ca2+) channels. Furthermore, MLSA
      failed to potentiate both thapsigargin- and anti-CD3 antibodies-induced
      capacitative calcium influx in Jurkat T cells. We observed that MLSA failed to
      affect the degree of phosphorylation of two MAP kinases, i.e., ERK1/ERK2,
      stimulated by anti-CD3 antibodies alone or phorbol 12-myristate 13-acetate (PMA)
      alone. In order to mimic co-stimulation of T cells, we stimulated them by both
      PMA and anti-CD3 antibodies. MLSA significantly curtailed the phosphorylation of
      ERK1/ERK2, stimulated by both PMA and anti-CD3 antibodies in Jurkat T cells. Also
      MLSA was found to reduce the transcription of IL-2 gene in PMA plus anti-CD3
      antibodies-activated Jurkat T cells. Our finding demonstrates that Ca2+ influx
      via CRAC channels, inhibition of ERK1/ERK2 phosphorylation and IL-2 gene
      transcription may be implicated in immunosuppressive effects of MLSA antigen.

PMID- 16583137
TI  - In vivo exposure of swiss albino mice to chronic low dose of dimethylnitrosamine
      (DMN) lowers poly-ADP-ribosylation (PAR) of bone marrow cell and blood lymphocyte
      proteins.
AB  - Efforts to identify an easy and convenient biomarker of carcinogenesis with
      potentials of application in mass screening program continue. In a series of
      investigations on mice exposed to different carcinogens, poly-ADP-ribosylation
      (PAR) of cellular proteins of different tissues has been shown to be a potential
      biomarker of carcinogenesis. Because blood based biomarker of carcinogenesis
      offers significant advantage in its use in a cancer screening program, this
      investigation was undertaken to find correlations between initiation of
      carcinogenesis and PAR of bone marrow cell (BMC) and blood lymphocyte (BL)
      proteins in mice chronically exposed to low dose of dimethylnitrosamine (DMN) for
      up to four weeks in vivo. The exposure was either alone or in combination with 3
      aminobenzamide (3-AB), an inhibitor of PAR. Total PAR of cellular proteins and of
      histone H1 protein were monitored by slot and Western blot immunoprobe assays,
      respectively. The PAR of total cellular proteins as well as of histone H1 was
      down-regulated in duration of exposure dependent manners. The results suggest
      that BMC and BL mirrored status of PAR in other tissues. This finding opens up
      the possibility of using PAR as a biomarker of carcinogenesis in a blood based
      test utilizing immunoprobe assay of cellular PAR.

PMID- 16583138
TI  - Effects of pharmacological preconditioning by emodin/oleanolic acid treatment
      and/or ischemic preconditioning on mitochondrial antioxidant components as well
      as the susceptibility to ischemia-reperfusion injury in rat hearts.
AB  - Using an ex vivo rat heart model of ischemia-reperfusion (I-R) injury, we
      examined the effect of pharmacological preconditioning by chronic treatment with
      emodin (EMD)/oleanolic acid (OA) at low dose (25 micromol/kg/day x 15) and/or
      ischemic preconditioning (IPC) (4 cycles of 5 min ischemia followed by 5 min of
      reperfusion) on myocardial I-R injury. The results indicated that EMD/OA
      pretreatment, IPC, or their combinations (EMD+IPC and OA+IPC) protected against
      myocardial I-R injury, as assessed by lactate dehydrogenase leakage and
      contractile force recovery. The cardioprotection was associated with a
      differential enhancement in mitochondrial antioxidant components. The combined
      EMD/OA and IPC pretreatment produced cardioprotective action in a semi-additive
      manner. This suggested that EMD/OA pretreatment and IPC protected against
      myocardial I-R injury via a similar but not identical biochemical mechanism.

PMID- 16583139
TI  - Modulation of cardiac sarcoplasmic reticulum calcium release by aenosine: a
      protein kinase C- dependent pathway.
AB  - We have already reported that A(3) adenosine receptor stimulation reduces [(3)H]
      ryanodine binding and sarcoplasmic reticulum Ca(2+) release in rat heart. In the
      present work we have investigated the transduction pathway responsible for this
      effect. Isolated rat hearts were perfused for 20 min in the presence of the
      following substances: 100 nM N(6)-(iodobenzyl)-adenosine-5'-N-methyluronamide (IB
      MECA), an A(3) adenosine agonist; 10 muM U-73122, a phospholipase C inhibitor; 2
      muM chelerythrine, a protein kinase C inhibitor. At the end of perfusion, the
      hearts were homogenized and [(3)H]-ryanodine binding was assayed. IB-MECA
      produced a significant decrease in ryanodine binding, which was abolished in the
      presence of chelerythrine but not in the presence of U-73122. RT-PCR experiments
      showed that ryanodine receptor gene expression was not affected by IB-MECA. In
      Western blot experiments, ryanodine receptor phosphorylation on serine 2809 was
      not modified after perfusion with IB-MECA. We conclude that modulation of SR
      Ca(2+) release channel by IB-MECA is dependent on protein kinase C activation.
      However, in this model protein kinase C activation is not due to phospholipase C
      activation. In addition, changes in ryanodine receptor gene expression or direct
      phosphorylation of the ryanodine receptor on serine 2809 residue do not appear to
      occur.

PMID- 16583140
TI  - Inhibitory cis-element-mediated decay of human papillomavirus type 16 L1
      transcript in undifferentiated cells.
AB  - Production of human papillomavirus type 16 major capsid protein L1 in
      undifferentiated cells is negatively regulated by several yet unidentified cis
      acting inhibitory RNA elements, among which a major element is located within the
      first 514 nucleotides of the L1-mRNA. By Northern blotting we examined effect of
      the major element on the steady-state level of mRNA transiently transcribed in
      293T cells from the firefly luciferase (Fluc) gene combined with the L1 DNA
      fragment encoding the major element. As reported previously, the element down
      regulated steady-state level of the mRNA. The most efficient down-regulation was
      achieved by insertion of the element near the 5' end of mRNA, resulting in an
      undetectable level of the mRNA. The longer the distance from the 5' end of the
      mRNA to the element, the weaker the down-regulation. The half-life of the mRNA
      having the element was similar to that of normal Fluc-mRNA. When the element near
      the 5' end was removed by splicing, the steady-state level of the resultant mRNA
      was raised to a readily detectable level. The steady-state level of RNA
      synthesized by RNA polymerase-I was not influenced by the presence of the
      element. Taken together, it is suggested that DNA region encoding the major
      inhibitory element does not disturb transcription and that the pre-mRNA is
      degraded by an RNA element-mediated mechanism after the splicing step in the
      course of mRNA maturation.

PMID- 16583141
TI  - Upregulation of glyoxalase I fails to normalize methylglyoxal levels: a possible
      mechanism for biochemical changes in diabetic mouse lenses.
AB  - Glyoxalase I is the first enzyme in a two-enzyme glyoxalase system that
      metabolizes physiological methylglyoxal (MGO). MGO reacts with proteins to form
      irreversible adducts that may lead to crosslinking and aggregation of lens
      proteins in diabetes. This study examined the effect of hyperglycemia on
      glyoxalase I activity and its mRNA content in mouse lens epithelial cells (mLE
      cells) and in diabetic mouse lenses and investigated the relationship between GSH
      and MGO in organ cultured lenses. mLE cells cultured with 25 mM D-glucose (high
      glucose) showed an upregulation of glyoxalase I activity and a higher content of
      glyoxalase I mRNA when compared with either cells cultured with 5 mM glucose
      (control) or with 20 mM L-glucose + 5 mM D-glucose. MGO concentration was
      significantly elevated in cells cultured with high D-glucose, but not in L
      glucose. GSH levels were lower in cells incubated with high glucose compared to
      control cells. Glyoxalase I activity and mRNA levels were elevated in diabetic
      lenses compared to non-diabetic control mouse lenses. MGO levels in diabetic
      lenses were higher than in control lenses. Incubation of lenses with buthionine
      sulfoximine (BSO) resulted in a dramatic decline in GSH but the MGO levels were
      similar to lenses incubated without BSO. Our data suggest that in mouse lenses
      MGO accumulation may occur independent of GSH concentration and in diabetes there
      is an upregulation of glyoxalase I, but this upregulation is inadequate to
      normalize MGO levels, which could lead to MGO retention and chemical modification
      of proteins.

PMID- 16583142
TI  - Increase in proliferation and differentiation of neural progenitor cells isolated
      from postnatal and adult mice brain by Wnt-3a and Wnt-5a.
AB  - Wnt signaling is implicated in the control of cell growth and differentiation
      during CNS development. These findings are based on studies of mouse and chick
      models. However, the action of Wnt signaling, at the cellular level, is poorly
      understood. In this study, we investigated the roles of Wnt-3a and Wnt-5a on
      differentiation and proliferation of postnatal neural progenitor cells (NPCs) in
      mice.NPCs were isolated from the subventricular zone (SVZ) of PN-1 and adult ICR
      mice. Plasmids containing active Wnt-3a or Wnt-5a were transfected to NPCs; their
      effects on the formation of neurospheres and differentiation into neuronal cells
      were then determined. Transfection of Wnt-3a and Wnt-5a plasmids promoted
      regeneration of neurospheres and differentiation into Map2-positive cells, and
      decreased differentiation into GFAP-positive cells. The conditioned media
      obtained from Wnt-3a or Wnt-5a transfected NPCs showed similar effects on
      differentiation of NPCs with cDNA transfection, although the magnitude of
      stimulatory effect was less than that by plasmid transfection. Wnt-3a and Wnt-5a
      transfection did not affect Brdu incorporation of neuronal or glial progenitors
      in differentiation media. Wnt-3a and Wnt-5a plasmid transfection and the
      treatment of Wnt-3a and Wnt-5a conditioned media increased beta-catenin levels in
      NPCs. Wnt-3a had a greater effect on beta-catenin levels than Wnt-5a. The PKC
      inhibitor completely blocked the Wnt-5a effect on neuronal differentiation in
      NPCs. These findings suggest that Wnt-3a and Wnt-5a each have distinct effects on
      the proliferation and differentiation of NPCs in postnatal mice.

PMID- 16583143
TI  - Novel mutations that enhance or repress the aggregation potential of SOD1.
AB  - Mutations in SOD1 cause FALS by a gain of function likely related to protein
      misfolding and aggregation. SOD1 mutations encompass virtually every domain of
      the molecule, making it difficult to identify motifs important in SOD1
      aggregation. Zinc binding to SOD1 is important for structural integrity, and is
      hypothesized to play a role in mutant SOD1 aggregation. To address this question,
      we mutated the unique zinc binding sites of SOD1 and examined whether these
      changes would influence SOD1 aggregation. We generated single and multiple
      mutations in SOD1 zinc binding residues (H71, H80 and D83) either alone or in
      combination with an aggregate forming mutation (A4V) known to cause disease.
      These SOD1 mutants were assayed for their ability to form aggregates. Using an in
      vitro cellular SOD1 aggregation assay, we show that combining A4V with mutations
      in non-zinc binding domains (G37R or G85R) increases SOD1 aggregation potential.
      Mutations at two zinc binding residues (H71G and D83G) also increase SOD1
      aggregation potential. However, an H80G mutation at the third zinc binding
      residue decreases SOD1 aggregation potential even in the context of other
      aggregate forming SOD1 mutations. These results demonstrate that various
      mutations have different effects on SOD1 aggregation potential and that the H80G
      mutation appears to uniquely act as a dominant inhibitor of SOD1 aggregation.

PMID- 16583144
TI  - Consumption of redox energy by glutathione metabolism contributes to hypoxia/
      reoxygenation-induced injury in astrocytes.
AB  - The role of glutathione during ischemia/reperfusion is still a controversial
      issue. Glutathione should exert beneficial effects in the situation of
      ischemia/reperfusion due to its antioxidative potency. However, increasing
      survival time after transient ischemia and hypoxia has been reported for
      glutathione depleted cells. This work was aimed to analyse whether glutathione
      metabolism essentially contributes to redox energy failure and subsequent cell
      damage during ischemia/reperfusion. For this purpose, primary astrocyte rich cell
      cultures were subjected to 1 h hypoxia followed by up to 4 h reoxygenation in
      combination with substrate deprivation and glutathione depletion. The ability of
      the cells to reduce MTT was used to quantify the redox power of the cells.
      Inhibition of glutathione synthesis by L-buthionine-(S,R)-sulfoximine (BSO)
      caused depletion of cellular glutathione within 24 h and increase in MTT
      reduction by about 10% under normoxic conditions. Reoxygenation following 1 h of
      hypoxia was associated with decrease in MTT reduction which was enhanced by
      substrate deprivation. Glutathione depletion reduced hypoxia-induced decrease in
      MTT reduction. Three hours of substrate deprivation prior hypoxia resulted in
      lower levels of MTT reduction during reoxygenaton. Our data suggest that in
      situations of oxidative stress such as ischemia/reperfusion, glutathione
      metabolism may causes decrease of the cellular redox energy below a threshold
      level required for basic cellular functions finally resulting in cell injury.

PMID- 16583145
TI  - Characterization, source identification and apportionment of selected metals in
      TSP in an urban atmosphere.
AB  - To understand the metal distribution characteristics in the atmosphere of urban
      Islamabad, total suspended particulate (TSP) samples were collected on daily 12 h
      basis, at Quaid-i-Azam University campus, using high volume sampler. The TSP
      samples were treated with HNO(3)/HClO(4) based wet digestion method for the
      quantification of eight selected metals; Fe, Zn, Pb, Mn, Cr, Co, Ni and Cd by
      FAAS method. The monitoring period ran from June 2001 to January 2002, with a
      total of 194 samples collected on cellulose filters. Effects of different
      meteorological conditions such as temperature, relative humidity, wind speed and
      wind direction on selected metal levels were interpreted by means of multivariate
      statistical approach. Enhanced metal levels for Fe (930 ng/m(3)), Zn (542
      ng/m(3)) and Pb (210 ng/m(3)) were found on the mean scale while Mn, Cr, Co and
      Ni emerged as minor contributors. Statistical correlation study was also
      conducted and a strong correlation was observed between Pb-Cr (r=0.611). The
      relative humidity showed some significant influence on atmospheric metal
      distribution while other meteorological parameters showed weak relationship with
      TSP metal levels. Regarding the origin of sources of heavy metals in TSP, the
      statistical procedure identified three source profiles; automobile emissions,
      industrial/metallurgical units, and natural soil dust. The metal levels were also
      compared with those reported for other parts of the world which showed that the
      metal levels in urban atmosphere of Islamabad are in exceedence than those of
      European industrial and urban sites while comparable with some Asian sites.

PMID- 16583146
TI  - Non-developed external oblique aponeurosis in inguinal hernia repair: a case
      report and discussion of the literature.
AB  - Open inguinal hernia repair is one of the most commonly performed operations in
      the world. It relies heavily on the presence of an inguinal canal formed by the
      external oblique aponeurosis and conjoint tendon. Variations of the anatomy of
      this region are rarely described. We describe a patient with bilateral inguinal
      hernias and missing external oblique aponeurosis. The patient underwent open
      repair secondary to previous abdominal surgery and the inability to obtain
      laparoscopic access. A medline search was performed and we provide a synopsis of
      the literature. At operation, no clear external oblique aponeurosis could be
      identified and large defects of the transversalis fascia were corrected. CT
      images of the anatomic variations are provided. To the best of our knowledge,
      combined abnormalities of the external oblique aponeurosis and transversalis
      fascia have not been described before.

PMID- 16583147
TI  - Etiology of inguinal hernia: ultrastructure of rectus sheath revisited.
AB  - In the last decade, in the search for abdominal-wall hernia etiology, attention
      has been brought to alterations in the connective tissue ultrastructure as the
      probable etiological factor. These may cause weakening of connective tissue,
      which in turn may form ground for hernia formation. To investigate this
      hypothesis in depth, we compared the ultrastructure of the connective tissue in
      hernia patients and the control group. The study group consisted of five patients
      with primary inguinal hernia (Nyhus II = 4, Nyhus IIIa = 1). Another five
      patients posted for emergency appendectomy created the control group. Tissue
      specimens, harvested intraoperatively from the rectus muscle sheath (RAMS) and
      fixed in 4% glutaraldehyde, underwent staining by the Masson, H-E and methylene
      blue techniques and were assessed by microscopy (light and scanning electron).
      The examinations showed significant differences in the rectus sheath
      ultrastructure. They included altered architecture, placement and quantity of
      collagen and elastic fibers, differences in the caliber of individual fibers and
      disrupted ground matter-to-fiber ratio. In patients with hernias, chaotic
      arrangement of collagen fibers was seen, as well as their thinning and a decrease
      in the general amount of elastic fibers, replaced by ground matter. Our research
      has shown significant differences in the structure of the RAMS between patients
      with hernias and healthy individuals. This supports the theory linking connective
      tissue alterations with the etiology of hernia, and stating that these
      alterations include connective tissue at locations distant from the hernia site
      as well, as the rectus sheath itself does not form a hernial defect.

PMID- 16583149
TI  - Is there a need for a mesh plug in inguinal hernia repair? Randomized,
      prospective study of the use of Hertra 1 mesh compared to PerFix Plug.
AB  - Although the mesh plug procedure is an effective operation, sutureless
      implantation of a single onlay mesh, if successful, would avoid the risks of plug
      related complications. One hundred patients with primary inguinal hernias were
      randomized to undergo PerFix Plug or Hertra 1 implantation. Mean duration of the
      operation was similar, 38 versus 35 min for plug and onlay mesh implantation,
      respectively (nonsignificant, NS). The level of postoperative pain and early
      complication rate was similarly low in both groups (NS). Recurrence rate was the
      same-2 patients in each group (4%)-all following large hernia repair. The level
      of long-term discomfort was low after each type of operation (NS). Implantation
      of the onlay mesh-Hertra 1 as compared to the use of PerFix Plug is simple, safe,
      and equally effective in small and medium inguinal hernia repair, suggesting that
      a plug device is not necessary for successful hernia surgery.

PMID- 16583150
TI  - Inguinal hernia repair: are ASA grades 3 and 4 patients suitable for day case
      hernia repair?
AB  - The American Society of Anaesthesiologists (ASA) 3 and 4 patients are generally
      considered unsuitable for day case hernia repair. There are minimal data
      regarding the acceptability of day case repair in these patients. This study
      analysed day case hernia rates with special emphasis on ASA grades. A
      retrospective review of all adult inguinal hernia repairs, under the care of one
      surgeon over a 9-year period, was performed. The data collected included
      demographics, ASA grades, the mode of anaesthesia and early complications. 577
      patients underwent inguinal hernia repair during the study period. 204 (35%)
      patients were ASA grade 1, 214 (37%) ASA grade 2, 132 (23%) ASA grade 3 and 29
      (5%) ASA grade 4. Day case rates for ASA grades 1-4 under LA were 86, 83, 77 and
      76% and under GA, 59, 36, 32 and 0%, respectively (P<0.05). There was no
      significant difference in the wound complication rates for different ASA grades
      under GA and LA. ASA grades 3 and 4 patients can undergo day case inguinal hernia
      repair, with similar complication rates to ASA grades 1 and 2 patients, when
      surgery is performed under local anaesthesia. ASA grades 3 and 4 patients need
      not be excluded from day case hernia repair.

PMID- 16583151
TI  - Main-chain smectic liquid-crystalline polymers as randomly disordered systems.
AB  - We report a high-resolution X-ray lineshape study of main-chain smectic polymers.
      The results indicate that the layer ordering differs fundamentally from the
      algebraic decay typical for other smectic liquid-crystalline systems. The
      lineshapes are best described by broad squared Lorentzians indicating some form
      of short-range correlations. However, several higher harmonics are observed,
      which excludes simple liquid-like short-range order. This behaviour is
      tentatively attributed to a random field of defects associated with entangled
      hairpins in the main-chain polymer structure.

PMID- 16583152
TI  - Depression in mothers of burned children.
AB  - The treatment of burned children needs to address also their psychic state. Since
      the child's emotional state depends heavily on the emotional state of its
      parents, especially the mother's, interest should also be focused on diagnosing
      and treating secondary psychiatric disorders in mothers of burned children. The
      AIM of this work was to study the prevalence of depression in mothers of burned
      children and its predicting factors. METHODS: The enrolment of mothers of burned
      children was done in the Burns Department, Ibn Rushd University Hospital in
      Casablanca, Morocco. Twenty-eight mothers of seriously burned children agreed to
      participate in this study. A psychiatric interview was conducted after informed
      consent was obtained. The mothers completed a questionnaire; the diagnosis was
      made according to DSM IV criteria using the Mini International Neuro-psychiatric
      Interview (MINI). The Hamilton Depression Rating Scale and the Hamilton Anxiety
      Rating Scale were used to evaluate respectively the intensity of depression and
      the level of anxiety. Social functioning was assessed by the Global Assessment of
      Functioning scale (GAF). The minimum time interval between the child's being
      burned and the interview with the mother was one month. RESULTS: The prevalence
      of depression was 35.7%, which is much higher in the mothers of burned children
      as compared to the general population. Several risk factors were found such as:
      several burned children or burn of the only child, severity and complications of
      burn, and the socio-economic level. CONCLUSION: Depression is a common disorder
      in mothers of burned children. Thus early screening for depression in mothers and
      psychological and psychiatric support must be provided in conjunction with the
      treatment of the burned child.

PMID- 16583153
TI  - Analysis of VP2 gene sequences of canine parvovirus isolates in India.
AB  - The epidemiology of canine parvovirus (CPV) infections in dogs in India was
      examined using 27 isolates collected during a two-year period. The VP2 genes of
      22 isolates were sequenced, and the deduced amino acid sequences were compared.
      The results indicated that the isolates belonged to CPV type 2a except four,
      which belonged to CPV type 2b. Comparison of the VP2 gene sequences revealed that
      the Indian isolates formed separate lineages distinct from the South East Asian
      isolates. The canine parvovirus isolates in India appear to evolve independently,
      and distinct geographical patterns of evolution could not be discerned in the
      isolates examined.

PMID- 16583154
TI  - Molecular analysis of Brazilian strains of bovine coronavirus (BCoV) reveals a
      deletion within the hypervariable region of the S1 subunit of the spike
      glycoprotein also found in human coronavirus OC43.
AB  - Bovine coronavirus (BCoV) causes enteric and respiratory dis- orders in calves
      and dysentery in cows. In this study, 51 stool samples of calves from 10
      Brazilian dairy farms were analysed by an RT-PCR that amplifies a 488-bp fragment
      of the hypervariable region of the spike glycoprotein gene. Maximum parsimony
      genealogy with a heuristic algorithm using sequences from 15 field strains
      studied here and 10 sequences from GenBank and bredavirus as an outgroup virus
      showed the existence of two major clusters (1 and 2) in this viral species, the
      Brazilian strains segregating in both of them. The mean nucleotide identity
      between the 15 Brazilian strains was 98.34%, with a mean amino acid similarity of
      98%. Strains from cluster 2 showed a deletion of 6 amino acids inside domain II
      of the spike protein that was also found in human coronavirus strain OC43,
      supporting the recent proposal of a zoonotic spill- over of BCoV. These results
      contribute to the molecular characterization of BCoV, to the prediction of the
      efficiency of immunogens, and to the definition of molecular markers useful for
      epidemiologic surveys on coronavirus-caused diseases.

PMID- 16583155
TI  - Transcriptional profile of shrimp white spot syndrome virus (WSSV) genes with DNA
      microarray.
AB  - In an attempt to obtain the transcriptional profile of shrimp white spot syndrome
      virus (WSSV) genes, DNA microarray analysis was performed using amplified DNA
      fragments of the WSSV genome that covered most of the presumptive open reading
      frames (ORFs). Total RNAs were extracted from WSSV-infected crayfish (Cambarus
      clarkii) and reverse transcribed into cDNA and labeled with 32P-dATP. The DNA
      microarray detected 81.1% of the ORFs, and 47 of these were transcribed at 6 h
      post infection, suggesting they may be early genes. Some early genes were further
      confirmed by temporal analyses of gene transcription. Results in this study
      indicated the effectiveness of DNA microarray for discovering early viral genes.

PMID- 16583156
TI  - The first immunoglobulin-like domain of porcine nectin-1 is sufficient to confer
      resistance to pseudorabies virus infection in transgenic mice.
AB  - Nectin-1 is an alphaherpesvirus receptor that binds to virion glycoprotein D
      (gD). Porcine nectin-1 mediates entry of pseudorabies virus (PRV), herpes simplex
      virus types 1 and 2 (HSV-1 and HSV-2), and bovine herpesvirus type 1 (BHV-1). The
      gD-binding domain of nectin-1 is the first or N-terminal immunoglobulin (Ig)-like
      domain of the entire ectodomain. Here, we generated three transgenic mouse lines
      expressing a fusion protein consisting of the first Ig-like domain of porcine
      nectin-1 and the Fc portion of porcine IgG1 to assess the antiviral potential of
      the first Ig-like domain of nectin-1 in vivo. All of the transgenic mouse lines
      showed significant resistance to PRV infection via intraperitoneal inoculation
      (survival rates of 67% to 100%). In the intranasal challenge, a lower but still
      significant protection was observed; 21% to 55% of the animals from the three
      transgenic mouse lines survived. The present results demonstrate that a soluble
      form of the first domain of porcine nectin-1 is able to exert a significant
      antiviral effect against pseudorabies virus infection.

PMID- 16583157
TI  - Dependence of the cognitive set on the involvement of the ventral and dorsal
      visual systems in cognitive activity.
AB  - Measures of the stability of a non-verbal visual set were compared in healthy
      human subjects in three series of experiments: 1) controls, in which a pair of
      set-forming stimuli (images of circles) were presented; 2) in the context of a
      test with a non-verbal set, subjects were presented with an additional task
      consisting of recognition of pseudowords (words); and 3) as before, but the
      additional task consisted of identifying the position of a target stimulus in a
      matrix of letters. There was a significant decrease in the stability (rigidity)
      of the non-verbal set on introduction of the additional task consisting of
      identifying the spatial position of a target stimulus; conversely, there was an
      increase in rigidity when the task consisted of recognizing the quality of a
      stimulus. Coherence analysis of cortical potentials in the alpha range showed
      that changes in the spatial organization of cortical electrical activity were
      significantly different, depending on the nature of the additional task: when the
      additional task involved recognition of a verbal stimulus, coherence connections
      were strengthened in the frontal-temporal-parietal areas of the right hemisphere;
      presentation in the context of a visuospatial task resulted in greater changes
      being observed in the anterior areas of the right hemisphere. It is suggested
      that the successful performance of mental functions requiring relatively rapid
      shifts in unconscious sets on changes in situation occurs in conditions of
      alternation of different types of cognitive tasks when cortical processing of
      visual information is mediated predominantly by one of the visual systems -
      either the ventral ("what?") or the dorsal ("where?") and, correspondingly, with
      the involvement of the anterior and posterior cortical selective attention
      systems.

PMID- 16583158
TI  - The effects of fluoxetine and its complexes with glycerrhizic acid on behavior in
      rats and brain monoamine levels.
AB  - The effects of the serotonin reuptake inhibitor fluoxetine (FL) and its complexes
      with glycyrrhizic acid (GA) in molar ratios of 1:1 (FLG-1) and 4:1 (FLG-4) on the
      behavior of adult rats were studied in an elevated cross maze, with measurement
      of brain monoamine and monamine metabolite levels. Agents were given via the
      intragastric route using a cannula at a dose of 25 mg/kg 1 h before testing. FL
      increased anxiety in the rats and decreased their movement activity; FLG-1 and
      FLG-4 had no effect on behavior. None of the agents affected brain serotonin
      content, though all decreased the levels of its metabolite 5-hydroxyindoleacetic
      acid in the hypothalamus, FLG-4 also decreasing this in the cortex. Noradrenaline
      levels in the hypothalamus were increased after FLG-1 and FLG-4. In the striatum,
      FL increased the levels of dopamine and its metabolite dihydroxyphenylacetic acid
      but had no effect on the level of transmitter catabolism. Unlike FL, FLG-1
      activated dopamine metabolism in the striatum. Overall, use of FL complexed with
      GA significantly modified its behavioral effects, which appears to be associated
      with the effects of FL and its complexes on the function of the monoaminergic
      systems involved in controlling behavior.

PMID- 16583159
TI  - Acquisition and extinction of a conditioned passive avoidance reflex in mice with
      genetic knockout of monoamine oxidase A.
AB  - We report here the results obtained from comparative analysis of learning and the
      dynamics of extinction of a conditioned passive avoidance response in mice with
      genetic knockout of monoamine oxidase A (MAO A) and the progenitor line C3H. Mice
      of both lines acquired the conditioned passive avoidance reaction efficiently.
      Mice with genetic knockout of MAO A were characterized by prolonged retention of
      reproduction of the memory trace, as compared with rapid extinction in C3H mice.
      Smaller numbers of transfers, and vertical rearings on days 7-13 and the numbers
      of glances into and rom the dark sector on days 11-13 of extinction in MAO A
      knockout mice appear to reflect their more marked fear reactions when confronted
      with the "dangerous" sector, along with increased anxiety, these facilitating
      longer-lasting retention of the memory trace.

PMID- 16583160
TI  - Features of the expression of the c-Fos gene along the rostrocaudal axis of the
      hippocampus in common voles after rapid training to solve a spatial task.
AB  - The level of expression of the c-Fos protein in neurons was used as a measure of
      the activation of transcription in the hippocampus of common voles (Microtus
      arvalis Pall.) after rapid spatial training. Stained Fos-positive cells were
      counted on 20 brain sections along the rostrocaudal axis of the hippocampus.
      Voles were trained to find the exit to their home cages through one of the arms
      of a modified eight-arm radial maze (using a 2-h series of six trials on one
      day). Animals were initially trained to leave the home cage via an arm not
      connected to the maze. Voles of the "active" control group were passed through
      the isolated arm into the home cage six times on the experimental day. Animals
      for the "passive" control for c-Fos levels were collected from their home cages.
      Significant increases in c-Fos expression in voles trained in the maze and the
      active control group, as compared with passive controls, were seen in all areas
      studied (hippocampal fields CA1 and CA3 and the dentate fascia). At the same
      time, a significant increase in the number of c-Fos-positive neurons in voles
      trained in the maze, as compared with the active controls, was noted only in the
      caudal hippocampus, no differences being seen in the rostral part. The greatest
      levels of activation were seen in the dentate fascia and field CA3. These results
      provide evidence for the heterogeneous functioning of the hippocampus along the
      rostrocaudal axis during training of voles to solve a spatial task.

PMID- 16583161
TI  - Frequency-amplitude characteristics of the EEG at different levels of
      consciousness.
AB  - The relationship between the level of consciousness and the level of brain
      activation was studied. The model providing gradual decreases in the level of
      consciousness consisted of states in the transition from waking to drowsiness.
      The measure of the level of consciousness, measured from subjects' self
      assessments, was the change in the content of consciousness, i.e., the intensity
      and quality of involuntarily arising mental processes. Each of the levels of
      consciousness was found to correspond to a defined EEG profile. The results
      showed that the lowest level of activation corresponded to the state in which the
      subjects noted inhibition of "inner speech" and "cessation of thoughts," this
      being associated with a change in the dynamics of the high-frequency EEG rhythm
      associated with the mechanism of transmission of cognitive information.

PMID- 16583162
TI  - Two phases of the contingent negative variation in humans: association with motor
      and mental functions.
AB  - The question of the relationship between contingent negative variation and the
      mechanisms controlling motor and mental functions has received inadequate study.
      The aims of the present work were to investigate the relationship between the
      early and late phases of contingent negative variation and the state of motor and
      mental functions in patients with Parkinson's disease and to study the effects of
      levodopa on contingent negative variation. Patients with Parkinson's disease
      showed significant decreases in the amplitudes and areas of both phases of
      contingent negative variation as compared with subjects of similar age.
      Correlation analysis demonstrated a negative relationship between the extent of
      impairment of coordinatory muscle interactions and the amplitudes of both phases
      of this variation (p < 0.01). There was a positive relationship between the
      magnitudes of both phases and the state of mental functions, particularly memory
      (p < 0.05). Treatment of patients with Parkinson's disease with levodopa was
      followed by a significant increase in the late phase (p < 0.05). The results
      obtained here provide evidence for the important role of structures supporting
      both direct motor control and mental functions in forming both phases of
      contingent negative variation. The greater effect of levodopa on the late phase
      of contingent negative variation suggests that the efferent system of the basal
      ganglia has a greater role in generating the late phase than in organizing the
      early phase of the variation.

PMID- 16583163
TI  - The effects of proinflammatory cytokines on the formation of behavior in early
      postnatal ontogenesis.
AB  - Studies were performed to investigate impairments to the formation of behavior
      arising as a result of increases in the proinflammatory cytokine interleukin
      1beta in early postnatal ontogenesis. The cytokine was given at pyrogenic or
      subpyrogenic doses for one week (the first, second, or third week of life).
      Behavior was assessed at prepubertal age and in the adult state in the open field
      and elevated cross maze tests. The greatest changes were seen in adolescent rats
      given interleukin-1beta during the first or third weeks of life. Impairments were
      seen after administration of pyrogenic and subpyrogenic doses of cytokine and
      were identical in females and males. Changes consisted of partial substitution of
      acts, increases in motor activity and decreases in investigative activity. After
      sexual maturation, these behavioral impairments were no longer seen.

PMID- 16583164
TI  - The degree of oxidative stress in the rat brain during ischemia and reperfusion
      in conditions of correction of the L-arginine-NO system.
AB  - The aim of the present work was to evaluate oxidative stress in the brains of
      rats during ischemia/reperfusion in conditions of correction of the L-arginine-NO
      system. Experiments on 128 rats with brain ischemia/perfusion in conditions of
      modulation of the L-arginine-NO system were used to study changes in the
      concentrations of (a) lipid peroxidation products, i.e., diene conjugates,
      malonic dialdehyde, and Schiff bases, and (b) antioxidant protection factors,
      i.e., retinol, alpha-tocopherol, and SH-groups. Administration of L-arginine and
      NO synthase inhibitors, i.e., the non-selective inhibitor N(omega)-nitro-L
      arginine methyl ester, the selective neuronal NO synthase inhibitor 7
      nitroindasole, and the selective inhibitor of inducible NO synthase S
      methylisothiourea, established that oxidative stress in rats with brain
      ischemia/perfusion is NO-dependent. NO formed by the various isoforms of NO
      synthase had different roles: hyperactivation of neuronal NO synthase was
      responsible for oxidative stress in both periods of brain ischemia/reperfusion,
      while increased inducible NO synthase activity was responsible in the late
      period.

PMID- 16583165
TI  - Baseline and evoked spike activity in neurons in embryonic transplants of the
      somatosensory cortex in rats.
AB  - The aim of the present work was to study the nature of the baseline and evoked
      spike activity of neurons in embryonic transplants four months after homotopic
      allotransplantation into the whisker representation zone of the somatosensory
      cortex of the recipient rat brain (the barrel field). These studies showed that
      the instantaneous mean spike frequency of neuron activity was decreased in neural
      transplants as compared with the somatosensory cortex of control rats, while the
      latent period of evoked cell activity was longer. In addition, the pattern of
      evoked activity in transplant neurons was characterized by an increased frequency
      of spike generation or alternation of periods of activation and decreased spike
      frequency with subsequent recovery to the initial level, this being similar to
      the pattern seen in neurons in the whisker representation zone of the
      somatosensory cortex in control rats.

PMID- 16583166
TI  - The state of the contralateral neuromotor apparatus of the rat in conditions of
      unilateral tenotomy.
AB  - The effects of unilateral transection of the Achilles tendon (tenotomy) on the
      electromyographic characteristics of the gastrocnemius muscle on the
      contralateral side were studied in rats. Motor responses, reflex responses, and
      motor unit spike activity in the contralateral gastrocnemius muscle were studied
      in baseline conditions and on afferent stimulation before and 10 days after
      tenotomy. Changes in the nature of motor unit spike activity and responses to
      afferent stimulation were observed. The results obtained here demonstrate
      increases in the excitability of individual motoneurons in the contralateral
      motor center of the gastrocnemius muscle after exclusion of the symmetrical
      gastrocnemius muscle from the overall pattern of movement activity.

PMID- 16583167
TI  - Correlates of measures of voluntary force with the functional state of the motor
      system.
AB  - Oscillation spectra were analyzed for prolonged isometric force recorded in
      healthy subjects of three age groups. Changes in the distributions of spectral
      components of the oscillations in force were noted, along with differences in the
      distributions of spectral density as exhaustion developed in the age groups. The
      amplitude-frequency ranges of changes in the spectral densities of oscillations
      in force characterized the activity at the suprasegmental and segmental levels of
      the motor system which support the voluntary control and automatic regulation of
      posture during the performance of movements. Correlates of the functional state
      of the motor system are discussed in terms of the voluntary and involuntary
      components of control. A significant increase in activity in the central
      structures of the movement control system was seen with the development of
      exhaustion, along with decreases in the frequency range of the activity of
      subcortical structures with age.

PMID- 16583168
TI  - Respiratory reactions to microinjection of bombesin into the solitary tract
      nucleus and their mechanisms.
AB  - Acute experiments were performed on urethane-anesthetized adult laboratory rats
      to investigate the effects of microinjections of 10(-13)-10(-4) M bombesin into
      the solitary tract nucleus on measures of respiration. Bombesin microinjections
      were found to stimulate respiration, inducing significant increases in the level
      of pulmonary ventilation, increases in respiratory volume, and increases in the
      bioelectrical activity of the inspiratory muscles. The most marked respiratory
      reactions were seen after intermediate peptide doses (10(-10)-10(-7) M). These
      respiratory effects of bombesin were found to result from its ability to suppress
      the inspiration-inhibiting Hering-Breuer reflex at the level of the solitary
      tract nucleus. The fact that ultralow doses of bombesin were active, along with
      the distribution of endogenous bombesin and its specific receptors in the
      solitary tract nucleus, and the ability of this peptide to modulate the Hering
      Breuer reflex all provide evidence that bombesin is involved in controlling
      respiration at the level of the dorsal structures of the respiratory center.

PMID- 16583169
TI  - Effects of glyprolines on stress-induced behavioral disorders in rats.
AB  - We report here studies on the antistress protective actions of three peptides of
      the glyproline family: Pro-Gly-Pro, Pro-Gly, and Gly-Pro. Stress (10 min forced
      swimming) evoked typical changes in the behavioral activity of rats in the
      elevated cross maze and hole board tests, providing evidence of a significant
      increase in anxiety and a decrease in the level of orientational-investigative
      activity. Prior (15 min before stress) i.p. administration of Pro-Gly-Pro and Gly
      Pro at a dose of 3.7 microM/kg significantly decreased the stress-induced
      behavioral abnormalities. This demonstrates the possibility that peptides Pro-Gly
      Pro and Gly-Pro may affect CNS structures involved in forming the body's
      responses to stress-inducing factors. Peptide Pro-Gly, at an equimolar dose, had
      no marked protective effect and only slightly decreased the stress-induced
      abnormalities in the behavior of rats.

PMID- 16583170
TI  - Hyperexcitability of pyramidal neurons in field CA1 in hippocampal slices from
      rats evoked by episodes of hypoxia: the roles of GABAA and GABAB receptors.

PMID- 16583171
TI  - Correlation between the sizes of Mauthner neurons and the preference of goldfish
      to turn to the right or left.
AB  - Three-dimensional computer reconstruction working from serial histological
      sections was used to study the morphology of the right and left Mauthner neurons
      (MN) in goldfish fry showing marked preferences to turn stably to the right or
      left in a narrow water channel or showing no asymmetry in their choice of side
      during turns. Visually, fish with left-sided motor asymmetry had larger MN on the
      right side, while fish with right-sided motor asymmetry had larger MN on the left
      side. Fish with symmetrical turns to the right and left showed no differences in
      MN size. Quantitative assessment of the MN of fish with preferences for turns to
      one side or the other revealed significant differences in the sizes of the
      somatic part, the axon hillock, and the axons of neurons located on the
      contralateral side of the medulla oblongata. Analysis of the statistical
      relationships between the functional (motor) asymmetry of fish and the
      morphological asymmetry of the somatic parts of MN in the same fish revealed a
      stable correlation (0.69) between these measures. Given that MN initiate
      unilateral turns of the body in free movement, the data obtained here lead to the
      conclusion that the larger neuron is more frequently activated in natural
      conditions as compared with the smaller, contralateral, neuron.

PMID- 16583172
TI  - Organization of the efferent projections of the pedunculopontine tegmental
      nucleus of the midbrain of the dog pallidum.
AB  - Studies of the pedunculopontinopallidal projections of the dog brain based on the
      retrograde axonal transport of horseradish peroxidase demonstrated that the
      compact zone (PPNc) and the lateral area of the diffuse zone (PPNd) of the
      pedunculopontine tegmental nucleus (PPN) of the midbrain project to the globus
      pallidus, entopeduncular nucleus, and ventral pallidum. The medial area of the
      PPNd, adjacent to the chiasm of the upper cerebellar peduncles and seen in other
      animals as the mesencephalic extrapyramidal area (MEA), projects only to the
      globus pallidus. In dogs, this area of the tegmentum is not a major source of
      projections to the striopallidum, such that it is inappropriate to regard it as a
      separate structure, comment being restricted to the topical organization of PPNd
      projections to the pallidum. Projection fibers to pallidal structures arise from
      both cholinergic and non-cholinergic PPN neurons.

PMID- 16583173
TI  - Prevalence of suspected diastolic dysfunction in patients with a clinical
      diagnosis of congestive heart failure.
AB  - INTRODUCTION: The prevalence of diastolic left ventricular (LV) dysfunction in a
      population presenting with a suspected diagnosis of congestive heart failure
      (CHF) is questionable and widely variable in the current literature. To minimize
      the disparity, we evaluated a large echocardiographic database to investigate the
      prevalence of systolic and suspected diastolic LV dysfunction in those with a
      suspected clinical diagnosis of CHF. METHODS: We retrospectively reviewed
      echocardiograms performed at our institution and evaluated the prevalence of
      abnormal LV systolic and diastolic function in those with a suspected clinical
      diagnosis of CHF. Diastolic dysfunction was defined as the presence of left
      atrial enlargement, left ventricular hypertrophy and reverse trans-mitral inflow
      ratio (E/A reversal). RESULTS: Of the 636 echocardiograms with CHF as the primary
      diagnosis, 461 had measured LV function. Normal LV systolic function were found
      in 238 of the patients (48%). Isolated diastolic LV dysfunction was found in 166
      patients (36%). Twelve percent of the patients with a suspected clinical
      diagnosis of CHF had normal LV systolic and diastolic function. CONCLUSION:
      Normal LV systolic function was seen in nearly one-half of the echocardiograms
      with a suspected clinical diagnosis of CHF. Suspected LV diastolic dysfunction
      was observed in one-third of the echocardiograms with a suspected clinical
      diagnosis of CHF.

PMID- 16583174
TI  - Non-invasive cardiac evaluation in heart failure patients using magnetic
      resonance imaging: a feasibility study.
AB  - BACKGROUND: To assess the feasibility of a fast, flow-insensitive magnetic
      resonance imaging (MRI) protocol in heart failure patients for the evaluation of
      cardiac function, cardiovascular anatomy, and myocardial viability. METHODS AND
      RESULTS: Thirty-two consecutive patients with left ventricular (LV) systolic
      dysfunction and 13 control subjects were prospectively evaluated with MRI. The
      exam consisted of cine imaging with a steady-state free precession sequence,
      followed by time-resolved, three-dimensional angiography and delayed, contrast
      enhanced imaging. Multiple LV parameters were evaluated, and the heart failure
      and control results were compared. In 12 patients, MRI-determined ejection
      fractions were compared to echocardiographic values. Additionally, a qualitative
      analysis of the cine images was performed. The cardiac MR evaluation yielded
      diagnostic-quality images in all subjects. Mean imaging time was 37 min. MRI
      demonstrated significant differences between the heart failure and control
      subjects in all parameters assessed (p < 0.05). MRI-determined ejection fractions
      correlated strongly with echocardiographic values (R = 0.75), although the limits
      of agreement were wide (-17.3%-18.3%). CONCLUSIONS: Using fast, flow-insensitive
      imaging techniques, MRI is feasible in heart failure for the derivation of more
      independent indices of cardiac status than any other non-invasive test. Although
      further investigation is warranted, MRI may prove uniquely helpful in heart
      failure diagnosis and management.

PMID- 16583175
TI  - Metabolic therapy for ischemic heart disease: the rationale for inhibition of
      fatty acid oxidation.

PMID- 16583176
TI  - Metabolic therapy for heart disease: impact of trimetazidine.

PMID- 16583177
TI  - Pharmacological stimulation of beta2-adrenergic receptors (beta2AR) enhances
      therapeutic effectiveness of beta1AR blockade in rodent dilated ischemic
      cardiomyopathy.
AB  - BACKGROUND: We have reported that beta2 adrenoreceptor (beta2AR) stimulation is
      anti-apoptotic, and has strong beneficial effect on cardiac remodeling in an
      experimental model of post myocardial infarction chronic heart failure (CHF) in
      rats. Here we investigate whether the addition of chronic pharmacological beta2AR
      stimulation enhances the therapeutic effects of beta1AR blockade on cardiac
      remodeling in the same model. METHODS AND RESULTS: Metoprolol, a beta1AR blocker,
      given alone (beta1) or in combination with beta2AR agonist, fenoterol
      (beta1beta2) were administered to rats via drinking water for 6 weeks, beginning
      2 weeks following permanent coronary ligation. Progressive left ventricular (LV)
      remodeling of untreated animals, assessed by repeated echocardiography, occurred
      during the observation time, i.e., 42% and 25% increases in end-systolic and end
      diastolic LV volumes respectively, 27% fall in ejection fraction, and 35% infarct
      expansion. Pressure-volume loop analyses at 2d and 8th post infarction weeks
      showed continuous deterioration of systolic and diastolic functions and arterio
      ventricular mismatch. Histological evaluation at the end of 8 weeks revealed the
      MI expansion and hypertrophy of cardiomyocytes. beta1beta2 prevented LV
      remodeling, MI expansion and cardiomyocytes hypertrophy to a greater degree than
      beta1, due, in large part, to a vasodilatory effect of beta2AR stimulation and
      thus improvement of arterio-ventricular mismatch. The abnormal diastolic
      performance improved only in beta1beta2. beta1beta2 treatment reduced myocardial
      apoptosis throughout myocardium, but beta1 reduced apoptosis only in the areas
      remote from MI. CONCLUSION: The therapeutic effects of chronic beta1AR blockade
      on cardiac remodeling of heart failure are enhanced and extended when
      supplemented with beta2AR stimulation.

PMID- 16583178
TI  - Expression of cytoskeletal, linkage and extracellular proteins in failing dog
      myocardium.
AB  - In the setting of chronic heart failure (HF), progressive left ventricular (LV)
      dysfunction and chamber remodeling may be due, in part, to altered expression and
      disorganization of cytoskeletal, linkage and extracellular proteins. This brief
      review describes changes in expression of cytoskeletal, linkage and extracellular
      protein using LV tissue obtained from dogs with progressive HF produced by
      multiple sequential intracoronary microembolizations. LV tissue samples from 6
      untreated HF dogs (LV ejection fraction 20% to 25%) and 3 normal dogs were used.
      Sections from freshly frozen tissue were prepared, immunostained for specific
      proteins and studies by confocal microscopy. In failing hearts, confocal
      microscopy showed disorganization of key cytoskeletal proteins that, when
      combined with the loss of myofilaments and sarcomeric skeleton, suggest
      substantial cardiomyocyte remodeling. Cardiomyocytes in areas bordering old
      infarcts invariably exhibited disorganization of alpha-actinin. The cytoskeleton
      protein desmin showed increased expression in areas of extensive fibrosis.
      Staining for pancadherin showed interruptions of intercalated disks in areas of
      intensive interstitial fibrosis. Observation of increased fibronectin and
      increased interstitial cellularity based on vimentin labeling is suggestive of
      ongoing fibrosis. Based on these findings, we conclude that the structural
      changes observed in failing LV myocardium of dogs with intracoronary
      microembolizations-induced HF are extensive and typical of those seen and
      previously described in LV myocardium of explanted failed human hearts. The
      observed structural changes in this experimental model of HF also support the
      notion that these cytoskeletal, linkage and extracellular disorganization of
      structural proteins may be important maladaptations that contribute, albeit in
      part, to the progression of LV dysfunction and remodeling characteristic of the
      HF state.

PMID- 16583179
TI  - Inhibition of mitochondrial permeability transition pores by cyclosporine A
      improves cytochrome C oxidase function and increases rate of ATP synthesis in
      failing cardiomyocytes.
AB  - BACKGROUND: We previously showed that mitochondrial respiratory function is
      abnormal in dogs with chronic heart failure (HF). Mitochondrial permeability
      transition pores (MPTP) can affect mitochondrial inner membrane potential
      (DeltaPsim) and mitochondrial function in normal cardiomyocytes. The potential
      impact of MPTP on DeltaPsim and mitochondrial respiratory function in HF has not
      yet been determined. We tested the hypothesis that cyclosporine A, a potent
      blocker of the MPTP, can improve mitochondrial function in HF. METHODS:
      Cardiomyocytes were isolated from the left ventricular myocardium of 7 dogs with
      HF produced by intracoronary microembolizations and from 7 normal dogs.
      Cardiomyocytes were treated for 24 hours with cyclosporine A. DeltaPsim,
      cytochrome c oxidase protein expression, mitochondrial cytochrome c oxidase
      dependent respiration (CDOR) and ATP synthesis were measured. RESULTS: DeltaPsim,
      protein expression of cytochrome c oxidase, CDOR and the rate of ATP synthesis
      were decreased in HF compared to normal controls. Inhibition of MPTP in failing
      cardiomyocytes with low dose of cyclosporine A (0.2 microM) increased DeltaPsim,
      preserved expression of cytochrome c oxidase, improved CDOR and the rate of ATP
      synthesis. CONCLUSION: MPTP opening contributes to the loss of mitochondrial
      function observed in the failing heart. Inhibition of MPTP opening represents a
      potential therapeutic target for the treatment of HF.

PMID- 16583181
TI  - Redo midurethral synthetic sling for female stress urinary incontinence.
AB  - Tension-free transvaginal tape (TVT) placement has recently become the preferred
      therapeutic approach for female stress urinary incontinence (SUI) in some
      centers. There are, however, no clearcut guidelines of how to treat patients in
      whom the procedure has failed. We describe our experience with repeat midurethral
      synthetic sling (MUS) implantation after a failed similar procedure. Twelve women
      (mean age 64.3 years) who had undergone a MUS procedure [TVT-9, intravaginal
      sling (IVS)-2, transobturator tape (TOT)-1] for SUI underwent a repeat MUS (TVT
      5, IVS-4, TOT-3) due to persistent or recurrent SUI. The time from the first to
      the second procedure was 1-48 months. Eleven out of 12 patients (91.7%) achieved
      full continence (mean follow-up of 23.2 months, range 14-44). We conclude that a
      repeat MUS for persistent or recurrent SUI is a viable option for patients after
      an unsuccessful MUS procedure.

PMID- 16583180
TI  - Clinical characteristics, demographics and prognosis of transient left
      ventricular apical ballooning syndrome.
AB  - BACKGROUND: Transient left ventricular apical ballooning syndrome also called
      Tako-Tsubo cardiomyopathy is defined as a syndrome consisting of stress induced
      apical ballooning of the left ventricle and normal coronary arteries. The
      majority of the published reports are case reports or case series with a small
      number of patients. The goal of this study was to perform statistical analysis of
      reported cases and case series in the literature in order to study demographic,
      clinical characteristics and prognosis of this syndrome. METHOD: A PubMed search
      of the terms transient left ventricular apical ballooning, Tako-Tsubo, takotsubo,
      and apical cardiomyopathy was conducted for this study. All reports that
      contained information about individual patients were included in the statistical
      analysis. RESULTS: The majority of the patients were women (93.5%). Asians were
      the largest group (57.2%) followed by Caucasians (40%). The presentations mimics
      an acute myocardial infarction. The most frequent presenting symptom was chest
      pain (65.9%) followed by dyspnea (16.2%). ST elevation was the most common ECG
      abnormality (87.5%). Contrary to most reports, this is not a benign disease with
      complications occurring in 18.9% and death in 3.2%. The most common complication
      was shock followed by left ventricular thrombus formation and congestive heart
      failure. CONCLUSION: Apical ballooning syndrome occurs most commonly in women and
      is associated with high complication rate. There are significant differences in
      presenting symptoms between race and gender which warrant further investigation.

PMID- 16583182
TI  - Prediction of successful voiding immediately after outpatient mid-urethral sling.
AB  - We set out to identify predictors of successful voiding immediately after
      outpatient mid-urethral sling. The charts of 126 patients who underwent an
      outpatient mid-urethral sling procedure were identified. Using discharge without
      a urinary catheter as the dependent variable, logistic regression analysis
      modeled the relationship of independent variables including demographic,
      preoperative urodynamic, and perioperative variables. Sixty-one percent of the
      patients passed their immediate postoperative voiding trial. Logistic regression
      analysis revealed that parity > or = 3, Valsalva leak point pressure > 60 cm
      H(2)O, and high preoperative anxiety remained independently associated with
      successful voiding. Identifying preoperative variables that are associated with
      successful voiding after mid-urethral sling may be useful in helping to
      accurately shape patient expectations and identify those most likely to benefit
      from preoperative teaching of self-catheterization.

PMID- 16583183
TI  - A comparison study of the efficacy and side effects of different light sources in
      hair removal.
AB  - Unwanted hairs are a common problem in which different light sources were
      developed as the treatment of choice. Alexandrite laser, diode laser, and intense
      pulsed light (IPL) were clinically used for this purpose with long-term scarce
      comparative results. The objective of the study was to compare the clinical
      efficacy, complications, and long-term hair reduction of alexandrite laser, diode
      laser, and IPL. Clinical trials on 232 persons using diode, alexandrite, laser
      and IPL were conducted. The number of sessions to reach optimal result varied
      between 3 and 7. Then the side effects were evaluated. Six months after the last
      session, optimal hair reduction was observed with no significant differences
      between the light sources, but a hair reduction was found to be higher using the
      diode laser. Side effects were observed with all light sources but more
      frequently with diode. Our findings indicate that all three light sources tested
      have similar effects on hair removal and in Iranian patients, using lower
      wavelengths minimizes the side effects.

PMID- 16583184
TI  - Monitoring the ups and downs of pulsed dye laser energy output.
AB  - The internal energy meter reading of a Chromos pulsed dye laser (PDL) set at 50%
      of maximum pumping energy was recorded at the start of every clinical session
      over an 898 day period and compared with the measurement from an Ophir Optronics
      'Nova' external energy meter. This quick and inexpensive process improved quality
      control procedures for the use of the PDL and enabled the performance of laser
      components such as the dye, pumping mechanism and optics to be monitored. The
      stability of the laser output energy was also monitored during three simulated
      clinics on days 665, 870 and 898. External energy meter readings were recorded
      every 100 pulses during each simulated clinic comprising six series of 500
      pulses. As the energy output was shown to be stable during each clinic (SD<4.7%)
      recalibration during treatments of up to 500 pulses with this laser was deemed to
      be unnecessary. However, it was noted that this output energy stability was
      maintained by varying the pumping energy from 42 to 88% of maximum. Subsequent
      measurements of pulse width conducted with an ET-2000 Silicon Photodetector
      demonstrated that although the nominal pulse width was 450 mus, this varied from
      240 to 390 mus as the pumping energy increased from 20 to 50%.

PMID- 16583185
TI  - Comparison of serum IL-1 beta, sIL-2R, IL-6, and TNF-alpha levels with disease
      activity parameters in ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic, inflammatory, rheumatological disease
      affecting primarily the sacroiliac joint and vertebral column, with an etiology
      that remains obscure. Cytokines are soluble proteins that have specific roles in
      inflammatory response, arranging the interaction between cells of the immune
      system both in natural and specific immune reactions. This study was planned to
      evaluate the relation between the level of cytokines and the clinical and
      laboratory findings of patients with AS compared to healthy subjects. In this
      study, we demonstrated increased serum levels of soluble interleukin-2 receptor
      (sIL-2R), Interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in
      patients with AS compared with healthy subjects. Only IL-1 beta levels were not
      increased in AS patients. We found a correlation between C-reactive protein and
      IL-6 levels and between erythrocyte sedimentation rate and sIL-2R, IL-6 and TNF
      alpha levels. Only the sIL-2R level was correlated with Bath AS Metrology Index
      and Bath AS Functional Index. We suggest that sIL-2R, IL-6, and TNF-alpha may
      have a role in the pathogenesis of AS and that their serum levels can be used as
      disease activity parameters and tools for diagnosis.

PMID- 16583186
TI  - Cure of chronic prostatitis presumably due to Enterococcus spp and gram-negative
      bacteria.

PMID- 16583187
TI  - Gottron's papules-like eruption developing under hydroxyurea therapy.
AB  - A 57-year-old white female developed a Gottron's papules (GP)-like eruption,
      without any of the other clinical or laboratory signs of dermatomyositis (DM).
      She was under hydroxyurea treatment for chronic myeloid leukemia at the time.
      Skin biopsy was compatible with seborrheic keratosis. Conditions presenting with
      GP but unrelated to DM are reviewed, with emphasis on hydroxyurea-induced skin
      lesions.

PMID- 16583188
TI  - Osteoarthritis susceptibility loci defined by genome scan meta-analysis.
AB  - Genome scans for osteoarthritis (OA) have yielded inconsistent results. The
      absence of replication of linkage might be due to the lack of power of individual
      studies. A meta-analysis of published data was performed to assess evidence for
      linkage of OA across genome scan studies. Three OA whole-genome scans including
      893 families with 3,000 affected individuals were used for genome scan meta
      analysis (GSMA). A total of five bins lie above 95% confidence level (P=0.05) and
      one bin is above 99% confidence level (P=0.01) in OA GSMA; bins 7.6 (7q34-7q36.3,
      P (sumrnk) =0.0035), 11.3 (11p12-11q13.4), 6.3 (6p21.1-6q15), 2.8 (2q31.1-2q34)
      and 15.3 (15q21.3-15q26.1). The highest summed bin was bins 7.6. In conclusion,
      the OA GSMA has shown that chromosome 7q34-7q36.3 have the highest summed rank
      and four additional loci with significant summed ranks across studies.

PMID- 16583189
TI  - New thoughts on the pathobiology of regimen-related mucosal injury.
AB  - BACKGROUND: Our understanding of the biological basis for mucosal barrier injury
      (mucositis) induced by cancer therapy with radiation or drugs continues to
      evolve. A patient's mucosal response to cancer therapy appears to be controlled
      by both global (i.e. gender, underlying systemic disease, race) and tissue
      specific (i.e. epithelial type, intrinsic endocrine system, local microbial
      environment, function) factors. CONCLUSION: Interactions of these elements,
      coupled with underlying genetic influences, most likely govern the risk, course
      and severity of regimen-related mucosal injury.

PMID- 16583191
TI  - [Morphology of drug induced liver damage].
AB  - Hepatotoxicity is a significant complication of therapeutic drug use. As ist can
      imitate nearly all hepatopathies, the diagnosis of drug-induced liver disease is
      difficult. Most often, it is a diagnosis of exclusion. The following
      morphological changes are known, dependent on the target cell type: acute and
      chronic hepatitis, granuloma formation, and fatty liver disease, cholestatic type
      acute and chronic liver damage with or without inflammation,or mixed forms of
      liver injury. Portal or perisinusoidal fibrosis can occur following each type of
      liver damage. Vascular changes or neoplasms are rare. Drug induced liver injuries
      are more likely induced by type B damage, which is not expected and cannot be
      reproduced in animal testing. Type A damage, which is known from toxicity assays,
      is less likely. A specific therapeutic regime is not available. Therefore, early
      recognition and cessation of the use of the drug is necessary.

PMID- 16583190
TI  - [Surgical management of abdominal injury].
AB  - PURPOSE: Accompanying abdominal injuries are frequent in multiply injured
      patients and are a common cause of death. A search of the literature was
      performed focusing on key aspects of initial surgical procedures in abdominal
      injury. METHODS: Literature was searched utilizing PubMed Medline, the Cochrane
      Central Register of Controlled Clinical Trials, and the German Institute for
      Medical Documentation and Information (DIMDI) database. The articles were
      classified according to the level of evidence following the suggestions of the
      Centre for Evidence Based Medicine. RESULTS: Vertical laparotomy should be
      favored for the initial surgical therapy of abdominal injury. Especially in
      instable patients, principles of "damage control surgery" should be applied. In
      case of hollow organ injury, a primary anastomosis should be made whenever
      possible. A hand suture is most suitable for this. DISCUSSION: Non-surgical
      treatment of blunt abdominal injury is gaining in importance. However, if a
      surgical intervention is recommended, especially in hemodynamic, instable
      patients, damage control principles should be favored.

PMID- 16583192
TI  - Postoperative liver enzyme abnormalities are related to staged restorative
      proctocolectomy.
AB  - BACKGROUND: Transient homeostatic derangements are found after major abdominal
      and pelvic surgery. We observed elevated liver function tests (LFTs) after
      restorative proctocolectomy (RPC). This study was undertaken to determine the
      etiology and implications of elevated LFTs before RPC and postoperatively.
      METHODS: One hundred and thirty-four RPC-patients were prospectively evaluated
      for LFT abnormalities. Patients were assigned to two groups: hand-sewn ileal
      reservoir after mucosoproctocolectomy (n=83) or stapled anastomosis (n=9), both
      with loop ileostomy and stapled anastomosis without loop ileostomy (n=42). Serum
      alanine-aminotransferase (ALAT) and alkaline phosphatases (ALP) were assessed
      preoperatively, 1-10 weeks postoperatively before loop ileostomy closure and 1-10
      weeks after ileostomy closure. These findings were correlated with anesthesia
      time, transfused blood volume, perioperatively administered drugs, and length of
      the diverted bowel while having a loop ileostomy. RESULTS: A large number of
      patients showed initial elevated serum ALAT and ALP levels, suggesting liver cell
      damage. There was a substantial and significant increase in ALAT and ALP in the
      first postoperative week. The values normalized within 2 weeks for the group
      without loop ileostomy, but not until after loop ileostomy closure in first
      group. A significant correlation as to length of diverted bowel (<0.05) while
      having a loop ileostomy was noted. When the length of diverted bowel was more
      than 105 cm, liver enzymes were higher than baseline levels (p<0.05) until after
      closure. CONCLUSIONS: Patients may develop elevated LFTs after RPC; however, its
      etiology and significance remains unclear. A loop ileostomy with RPC seemed to
      delay the normalization. Consideration of further diagnostic imaging may be
      indicated to exclude other liver pathology such as sclerosing cholangitis.

PMID- 16583193
TI  - Perioperative blood transfusions increase infectious complications after ileoanal
      pouch procedures (IPAA).
AB  - BACKGROUND AND PURPOSE: Assessment of risk factors associated with the use of
      perioperative allogeneic blood transfusion and the effect of transfusion on
      infectious complications after ileal pouch-anal anastomosis (IPAA). METHODS: All
      patients included had IPAA with ileostomy. They were divided into two groups:
      transfused (TRAN); nontransfused (NON). Data included age, gender, preoperative
      anemia (Hgb <9 l g/dl), operative blood loss, transfusion volume, incidence of
      postoperative infectious or anastomotic complications, and length of stay (LOS).
      RESULTS: The 1,202 patients eligible for the study were divided into: TRAN = 240
      patients and NON = 962 patients. The patient age, sex, and preoperative steroid
      use were similar in both groups. Significantly, more patients in the TRAN group
      were anemic preoperatively (32 vs 11%; p<0.05) and the preoperative Hgb level was
      significantly lower in the TRAN (12.07; p<0.05 vs 13.34 g/dl). Transfusion was
      required more frequently in anemic patients (p<0.001). The overall infection rate
      was significantly higher in the TRAN (48.75 vs 11.22%, p<0.001), Anastomotic
      separation (10.83 vs 3.32%, TRAN and NON, respectively; p<0.001) and fistula
      formation percentage (20.8 vs 4.46%, TRAN and NON, respectively; p<0.001) was
      significantly higher in the TRAN group. Pelvic sepsis also occurred more frequent
      in TRAN (22.9 vs 4.2%, TRAN and NON, respectively; p<0.001). The incidence of any
      infectious complication at any site was higher in anemic patients irrespective of
      transfusion status (18.2 vs 2.8%, p<0.05). Transfusion was the only significant
      independent risk factor for postoperative infections. LOS was adversely affected
      by an infectious complication (9 vs 7 days, p<0.001). CONCLUSIONS: Preoperative
      anemia is a significant risk factor for perioperative transfusion with
      significant increase in postoperative infectious complications and anastomotic
      complications after IPAA. Strategies to correct preoperative anemia, refine
      indications for transfusion, and define the use of blood salvage techniques may
      be helpful in decreasing this risk.

PMID- 16583194
TI  - Polyethylene glycol solution (PEG) plus contrast medium vs PEG alone preparation
      for CT colonography and conventional colonoscopy in preoperative colorectal
      cancer staging.
AB  - PURPOSE: This study evaluated the usefulness of combined polyethylene glycol
      solution plus contrast medium bowel preparation (PEG-C preparation) followed by
      dual-contrast computed tomography enema (DCCTE) and conventional colonoscopy. The
      main purpose of these examinations is the preoperative staging of already known
      tumors. MATERIALS AND METHODS: One hundred patients with colorectal tumors were
      alternately allocated to either a polyethylene glycol solution preparation (PEG
      preparation) group (n=50) or a PEG-C preparation group (n=50) before undergoing
      conventional colonoscopy and computed tomographic (CT) colonography. After
      conventional colonoscopy, multidetector row CT scans were performed. Air images
      were reconstructed for both groups; contrast medium images were additionally
      reconstructed for the PEG-C preparation group. DCCTE images were a composite of
      air images and contrast medium images without use of dedicated electronic
      cleansing software. Quality scores (the presence or absence of blind spots of the
      colon) were compared between the two groups. RESULTS: Complete tumor images were
      obtained by DCCTE for all 50 (100%) lesions in the PEG-C preparation group, as
      compared with only nine of the 50 lesions (18%) in the PEG preparation group (air
      contrast CT enema). The overall quality score in the PEG-C preparation group was
      significantly better than that in the PEG preparation group (P<0.0001).
      CONCLUSIONS: DCCTE showed the entire colon without blind spots in nearly all
      patients in the PEG-C preparation group because the areas under residual fluid
      were reconstructed as contrast medium images. DCCTE and conventional colonoscopy
      after PEG-C preparation are feasible and safe procedures that can be used for
      preoperative evaluation in patients with colorectal cancer.

PMID- 16583195
TI  - Manometric study in ulcerative colitis patients with modified ileal pouch--anal
      anastomosis.
AB  - BACKGROUND AND AIMS: Sphincter-saving operations and construction of intestinal
      reservoirs aim at additional improvement quality of life of patients with
      restorative proctocolectomy. The conventional ileoanal anastomosis affects the
      function of the anal sphincters. There is a need for operative techniques that
      provide sufficient intraluminal anal pressure and thus a better postoperative
      continence and quality of life. MATERIALS AND METHODS: Ileal pouch-anal
      anastomosis (IPAA) after restorative proctocolectomy was carried out in 42
      consecutive ulcerative colitis patients (age range: 19-55 years and mean age of
      35.52 years). There were 17 males (40.48%) and 25 females (59.52%). IPAA was
      performed at dentate line, according to a standard method, in 20 patients (47.62%
      of the cases; mean age of 35.20 years), 19 of which were in 1986-1995 and one
      patient in 1998. In 1996-2002, however, IPAA was performed after plicating the
      demucosed segment of rectal residual in 22 patients (52.38% of the cases; mean
      age of 35.82 years). This modification consisted in strengthening the internal
      anal sphincter by creation of a smooth muscle cuff through plication of a
      mucosectomized segment of rectal residual. The basal anal-canal and squeeze
      pressures were recorded prior to the operation as well as 1 month afterwards and
      then every 6 months for 2 years. Kelly-Hohlschneider's continence scores after
      Herold's modification were applied in 14 consecutive patients. RESULTS: Thanks to
      strengthening the internal anal sphincter by this segment, the basal pressure
      increased from a preoperative value of 68+/-6 mmHg up to 80+/-6 mmHg at the end
      of the second postoperative year (P<0.001). This favourable effect could be
      explained with the additional contractile potential of the plicated rectal
      segment resulting from the interference of the contractile potential of the
      internal anal sphincter with that of the smooth muscle cuff. CONCLUSION: The
      modified IPAA creates a novel and probably functionally active anatomical
      substrate. The basal anal-canal pressure is maintained sufficiently high through
      the tone of the smooth muscle cuff and internal anal sphincter. Our preliminary
      results suggest that the presented technique for performing IPAA may contribute
      to better functional results.

PMID- 16583196
TI  - Is there a role for neoadjuvant treatment with Gleevec for large rectal
      gastrointestinal stromal tumors?

PMID- 16583197
TI  - A case of delayed rectal stenosis from severe pelvic fracture with massive
      bleeding successfully treated by bilateral internal iliac TAE: report on a
      patient survival.

PMID- 16583198
TI  - The formation of endo-complexes between calixarenes and amines--a
      reinvestigation.
AB  - The formation of an endo-complex between p-allylcalix[4]arene and t-butylamine
      was described by Gutsche in 1985. However, for a comparable system, it has been
      shown using NOE methods that the amine does not reside inside the calix. Instead,
      an exo-calix complex is formed. A reevaluation suggests that the previous
      conclusion is an artifact due to improper NMR-data processing. DFT (RB3LYP/6
      31G(d)) calculations confirm the higher stability of the exo-complex over its
      endo-counterpart.

PMID- 16583199
TI  - Computational approaches for modeling human intestinal absorption and
      permeability.
AB  - Human intestinal absorption (HIA) is an important roadblock in the formulation of
      new drug substances. Computational models are needed for the rapid estimation of
      this property. The measurements are determined via in vivo experiments or in
      vitro permeability studies. We present several computational models that are able
      to predict the absorption of drugs by the human intestine and the permeability
      through human Caco-2 cells. The training and prediction sets were derived from
      literature sources and carefully examined to eliminate compounds that are
      actively transported. We compare our results to models derived by other methods
      and find that the statistical quality is similar. We believe that models derived
      from both sources of experimental data would provide greater consistency in
      predictions. The performance of several QSPR models that we investigated to
      predict outside the training set for either experimental property clearly
      indicates that caution should be exercised while applying any of the models for
      quantitative predictions. However, we are able to show that the qualitative
      predictions can be obtained with close to a 70% success rate.

PMID- 16583200
TI  - Production of lipase by high cell density fed-batch culture of Candida
      cylindracea.
AB  - Candida cylindracea NRRL Y-17506 was grown to produce extracellular lipase from
      oleic acid as a carbon source. Through flask cultures, it was found that the
      optimum initial oleic acid concentration for cell growth was 20 g l(-1). However,
      high initial concentrations of oleic acid up to 50 g l(-1) were not inhibitory.
      The highest extracellular lipase activity obtained in flask culture was 3.0 U ml(
      1) after 48 h with 5 g l(-1) of initial oleic acid concentration. Fed-batch
      cultures (intermittent and stepwise feeding) were carried out to improve cell
      concentration and lipase activity. For the intermittent feeding fed-batch
      culture, the final cell concentration was 52 g l(-1) and the extracellular lipase
      activity was 6.3 U ml(-1) at 138.5 h. Stepwise feeding fed-batch cultures were
      carried out to simulate an exponential feeding and to investigate the effects of
      specific growth rate (0.02, 0.04 and 0.08 h(-1)) on cell growth and lipase
      production. The highest final cell concentration obtained was 90 g l(-1) when the
      set point of specific growth rate (mu(set)) was 0.02 h(-1). High specific growth
      rate (0.04 and 0.08 h(-1)) decreased extracellular lipase production in the later
      part of fed-batch cultures due to build-up of the oleic acid oversupplied. The
      highest extracellular lipase activity was 23.7 U ml(-1) when mu(set) was 0.02 h(
      1), while the highest lipase productivity was 0.31 U ml(-1) h(-1) at mu(set) of
      0.08 h(-1).

PMID- 16583201
TI  - [Systemic manifestations of rheumatoid arthritis].
AB  - Extra-articular manifestations of rheumatoid arthritis are gaining in importance
      both in rheumatology and other specialities. This report provides information on
      various organ manifestations and interactions between mere disease-related
      symptoms and therapeutic effects. Diagnostic radiology plays a crucial role in
      finding the diagnosis, planning and monitoring of treatment, early detection of
      complications and drug-related adverse events.

PMID- 16583202
TI  - High-performance thin-layer chromatographic analysis of neutral lipids and
      phospholipids in Biomphalaria glabrata patently infected with Echinostoma
      caproni.
AB  - This study examined the effects of larval trematode infection on the neutral
      lipid and phospholipid content of Biomphalaria glabrata patently infected with
      the daughter rediae of Echinostoma caproni. Uninfected snails were used as
      matched controls. As determined by qualitative high-performance silica gel thin
      layer chromatography (HPTLC), the major neutral lipids present in the whole
      bodies and digestive gland-gonad complexes in both snail populations were free
      sterols, free fatty acids, and triacylglycerols, and the major polar lipids were
      phosphatidylcholine and phosphatidylethanolamine. Quantitative analysis by HPTLC
      with visible and UV scanning reflectance densitometry showed no significant
      differences in the concentrations of these lipids in whole bodies of infected
      snails vs the controls, but the concentration of triacylglycerols in the infected
      digestive gland-gonad complex was significantly less than that of the uninfected.
      No qualitative differences in neutral lipids and phospholipids in shell or plasma
      samples were found between infected vs uninfected snails.

PMID- 16583203
TI  - Falcaustra donanaensis sp. nov. (Nematoda: Kathlaniidae) a parasite of Mauremys
      leprosa (Testudines, Bataguridae) in Spain.
AB  - Falcaustra donanaensis sp. nov. (Nematoda, Kathlaniidae) from the large intestine
      of Mauremys leprosa (Testudines, Bataguridae) is described. By the absence of
      pseudosucker, arrangement of the male caudal papillae and the size of the
      spicules Falcaustra donanaensis sp. nov. resembles only to Falcaustra
      washingtonensis [Bursey and Aker (2001) J Parasitol 87:1082-1084], a species from
      Ambistoma tigrinum melanostictum in the Nearctic Region. Papillae pattern in the
      male of F. washingtonensis is similar to F. donanaensis, but differs by the
      presence of a median papilla in the American species, length of pharynx, spicule,
      and gubernacle in males, size of eggs, and number of eggs in female. This is the
      first species of Falcaustra reported in freshwater turtles in the Iberian
      Peninsula.

PMID- 16583204
TI  - Visual diagnosis of Taenia saginata cysticercosis during meat inspection: is it
      unequivocal?
AB  - A total of 267 cysts were collected from March to December 2004 from two main
      abattoirs in northern Germany. The cysts were classified by the usual
      organoleptic methods during meat inspection as Cysticercus bovis. The reported
      prevalence of cysticercosis in the abattoirs was 0.48 and 1.08%, respectively.
      The cysts were examined macroscopically for description of their morphology and
      constituents and classified as viable or degenerating (dead). The DNA was
      extracted from these cysts and subjected to polymerase chain reaction (PCR) for
      evaluation of the detection methods used and to make certain that the cysts did
      indeed belong to C. bovis, as indicated at the slaughterhouses. Two sets of
      primers were used with different sensitivity levels. The first, HDP1, was able to
      detect 200 fg of Taenia saginata DNA and 100 pg of C. bovis DNA. The other primer
      set, HDP2, was able to detect 1 pg of T. saginata DNA and 1 ng of C. bovis DNA.
      No more than 52.4% of the samples tested positive for C. bovis in the PCR using
      both primers, while 20% of the viable cysts and 49.2% of the degenerating cysts
      tested negative with both primers.

PMID- 16583205
TI  - [Project selection and protocol design in the Study Centre of the German Surgical
      Society].
AB  - BACKGROUND: The Study Centre of the German Surgical Society (SDGC) designs,
      conducts, and analyses multicentre randomised controlled surgical trials. The aim
      of this paper is to present the decision-making process and responsibilities of
      the SDGC from submission of a study idea to full protocol development in order to
      achieve transparency in trial selection. METHODS: The process is divided into
      four steps. Study ideas can be submitted electronically by members of the German
      Surgical Society using a form via the homepage of the institution. Firstly, ideas
      are screened by staff members within 4 weeks for methodological and clinical
      relevance. Feasible and novel ideas are then converted to trial outlines in
      cooperation with the submitting surgeon. As a third step, the Steering Committee
      of the SDGC decides whether to accept the project using a list of defined
      criteria. Finally, the SDGC draws up a full protocol together with the submitting
      surgeon. All ideas and decisions are accessible via the SDGC homepage.
      CONCLUSIONS: The process described should help in the selection of relevant
      projects, acquisition of grants, and maintenance of transparency in trial
      selection and the protocol development process.

PMID- 16583206
TI  - New insights from X-ray photoelectron spectroscopy into the chemistry of covalent
      enzyme immobilization, with glutamate dehydrogenase (GDH) on silicon dioxide as
      an example.
AB  - A three-step process for immobilization of glutamate dehydrogenase (GDH) on the
      surface of silicon dioxide has been studied by X-ray photoelectron spectroscopy
      (XPS). The enzyme layer was deposited on the silicon dioxide surface after first
      exposing the surface to 3-aminopropyltriethoxysilane (3-APTS) and reacting the
      silylated surface with glutaraldehyde (GA). Fine XPS analysis, performed after
      each step of the chemical procedure, revealed unknown details of the step-by-step
      construction of the enzyme layer under different experimental conditions.

PMID- 16583208
TI  - Chemiluminescence determination of metformin based on hydroxyl radical reaction
      and molecularly imprinted polymer on-line enrichment.
AB  - A novel and simple chemiluminescence (CL) method has been developed and validated
      for determination of metformin. This method is based on hydroxyl radical
      chemiluminescence-the hydroxyl radical generated by reaction of Cu(II) and
      hydrogen peroxide oxidizes rhodamine B (RhB) to produce weak CL which can be
      enhanced by metformin. At the same time, metformin molecularly imprinted polymer
      (MIP) was synthesized. After enrichment based on the selectivity of metformin
      MIP, the CL method was successfully applied to the determination of metformin in
      human serum. The linear range was from 1.0 x 10(-8) to 1.0 x 10(-6) g mL(-1) and
      the detection limit was 4 x 10(-9) g mL(-1). The relative standard deviation at
      2.0 x 10(-7) g mL(-1) by use of MIP was 3.67% (n = 7).

PMID- 16583209
TI  - Analytical challenge. Solution to DNA sequencing challenge.

PMID- 16583210
TI  - Both Th1 and Th2 chemokines are elevated in sera of patients with autoimmune
      blistering diseases.
AB  - Although chemokines are critical elements for the selective attraction and
      activation of various leukocyte subsets in the inflammatory process, there are
      few findings concerning T helper (Th) 1 or Th2 chemokines in autoimmune
      blistering disease (ABD). To determine whether serum levels of chemokines that
      are preferentially chemotactic for Th1 (monokine induced by IFN-gamma
      (MIG/CXCL9)) and Th2 (thymus and activation regulated chemokine (TARC/CCL17) and
      macrophage derived chemokine (MDC/CCL22)) cells were elevated and whether they
      correlated with the clinical features in patients with ABD. Serum chemokine
      levels were examined using ELISA in patients with pemphigus vulgaris (PV, n=19),
      pemphigus foliaceous (PF, n=14), or bullous pemphigoid (BP, n=27) and normal
      controls (n=20). Serum MIG levels were significantly higher in patients with PV,
      PF, or BP than those in the control subjects. Serum levels of TARC and MDC were
      also significantly elevated in patients with PV, PF, or BP relative to the normal
      controls. Among the ABD subgroups, the levels of each chemokine tended to be
      higher in BP patients than in PV patients. Furthermore, serum TARC levels
      correlated positively with serum IgE levels in patients with ABD. Levels of TARC,
      MDC, and MIG were significantly decreased after treatment when the skin lesions
      disappeared in these patients. Furthermore, serum MIG levels correlated
      positively with serum levels of TARC and MDC in the ABD patients. These results
      suggest that both a Th1 chemoattractant MIG and Th2 chemoattractants, TARC and
      MDC, cooperatively play a role in the development of ABD.

PMID- 16583211
TI  - Identification and functional perspective of a novel HLA-A allele: A*0279.
AB  - A novel HLA-A allele, HLA-A*0279, was identified using PCR-SSP and PCR-SBT
      methods. It is inheritable. HLA-A*0279 differs from HLA-A*020601 by a single
      nucleotide at position 497 in exon 3, leading to an amino acid change from
      Threonine to Isoleucine at the alpha2 helix of HLA molecule. To investigate
      whether the altered amino acid residue could affect its peptide-binding
      repertoire, we compared the predicted crystal structure of HLA-A*020601 and HLA
      A*0279 by Swiss-PdbViewer software analysis. We found that the crystal structure
      of the two molecules is very similar except for a difference in the number of
      hydrogen bonds they can possibly form, which in turn could affect their
      structural stability. To test whether HLA-A*0279 has the ability to cross-present
      A*0201 - restricted peptides to T cells, the full lenght cDNA of HLA-A*0201, -A*
      020601 and -A*0279 were respectively transfected into COS-7 cells, which were
      then used as targets in IFN-gamma release Elispot assay. A*2079 was found to be
      able to present A*0201- restricted peptides to and induce the response of CTL,
      thus it can be classified as member of the HLA-A2 functional supertype family.
      This finding would benefit the design of peptide vaccines to be applied in
      broader populations.

PMID- 16583212
TI  - Magnetic resonance imaging of orbital tumors.
AB  - This contribution provides an overview of diseases of eye and orbit and their
      appearance on magnetic resonance imaging. In recent years the diagnosis of eye
      and orbit pathology has profited significantly from increasingly sophisticated
      technical developments in the field of tomographic methods. Due to the small size
      of the examination area the improvement in spatial resolution and soft tissue
      contrast leads to an increase in image quality. In most clinical questions
      concerning eye and orbit pathologies magnetic resonance imaging is superior to
      computed tomography and should be early performed.

PMID- 16583213
TI  - Contemporary issues in the diagnosis of prostate cancer for the radiologist.
AB  - Prostate cancer diagnostic techniques have improved considerably in recent years,
      but they must yet be optimised to ensure cancer detection at a potentially
      curable stage. Arrangements for prostate biopsy vary throughout Europe, and
      prostate biopsy may be undertaken by urologists or radiologists. This review
      discusses current issues relevant for radiologists involved in the detection of
      early prostate cancer. Prostate biopsy should be based on a systematic approach
      involving 8-12 cores obtained with peri-prostatic infiltration of local
      anaesthetic. Quality issues being considered by the United Kingdom Prostate
      Cancer Risk Management Programme are discussed.

PMID- 16583214
TI  - Correlative assessment of cerebral blood flow obtained with perfusion CT and
      positron emission tomography in symptomatic stenotic carotid disease.
AB  - Twelve patients with ICA stenosis underwent dynamic perfusion computed tomography
      (CT) and positron emission tomography (PET) studies at rest and after
      acetazolamide challenge. Cerebral blood flow (CBF) maps on perfusion CT resulted
      from a deconvolution of parenchymal time-concentration curves by an arterial
      input function (AIF) in the anterior cerebral artery as well as in both anterior
      choroidal arteries. CBF was measured by [(15)O]H(2)O PET using multilinear least
      squares minimization procedure based on the one-compartment model. In
      corresponding transaxial PET scans, CBF values were extracted using standardized
      ROIs. The baseline perfusion CT-CBF values were lower in perfusion CT than in PET
      (P>0.05). CBF values obtained by perfusion CT were significantly correlated with
      those measured by PET before (P<0.05) and after (P<0.01) acetazolamide challenge.
      Nevertheless, the cerebrovascular reserve capacity was overestimated (P=0.05)
      using perfusion CT measurements. The AIF selection relative to the side of
      carotid stenosis did not significantly affect calculated perfusion CT-CBF values.
      In conclusion, the perfusion CT-CBF measurements correlate significantly with the
      PET-CBF measurements in chronic carotid stenotic disease and contribute useful
      information to the evaluation of the altered cerebral hemodynamics.

PMID- 16583215
TI  - Combined T2* and T1 measurements for improved perfusion and permeability studies
      in high field using dynamic contrast enhancement.
AB  - This study analyzed the T2* effect of extracellularly distributed gadolinium
      contrast agents in arterial blood during tumor studies using T1-weighted
      sequences at high field strength. A saturation-prepared dual echo sequence with
      echo times of 1.5 and 3.5 ms was employed at 3 T to simultaneously characterize
      T1 and T2* of arterial blood during bolus administration of Gd-DTPA in 28
      patients with body tumors. T2* effect and T1 effect of Gd-DTPA on image intensity
      of whole blood were calibrated in human blood samples with different
      concentrations of contrast agent. T2* was used to estimate concentration near the
      peak of the bolus. T1 was used to measure lower concentrations when T2* was not
      significant. T2* was measurable on calibration curves for Gd-DTPA concentrations
      higher than 4 mM. This concentration was exceeded in 18 patients. The mean signal
      intensity reduction because of T2* effect was estimated at 22+/-14% of the T2*
      compensated signal. Using T2* measurements reduced underestimations of peak
      arterial Gd-DTPA concentration (59 +/- 38%) and overestimation of permeability
      Ktrans (58%). The T2* effect of gadolinium contrast agents should therefore be
      accounted for when performing tumors study with T1-weighted sequences at high
      field strength.

PMID- 16583216
TI  - MDCT urography: retrospective determination of optimal delay time after
      intravenous contrast administration.
AB  - The optimal delay time after intravenous (i.v.) administration of contrast medium
      (CM) for opacification of the upper urinary tract (UUT) for multidetector
      computed tomography urography (MDCTU) was investigated. UUT opacification was
      retrospectively evaluated in 36 four-row MDCTU examinations. Single- (n=10) or
      dual-phase (n=26) MDCTU was performed with at least 5-min delay after i.v. CM.
      UUT was divided into four sections: intrarenal collecting system (IRCS),
      proximal, middle and distal ureter. Two independent readers rated UUT
      opacification: 1, none; 2, partial; 3, complete. Numbers and percentages of
      scores, and the 5%, 25%, 50%, 75% and 95% percentiles of delay time were
      calculated for each UUT section. After removing diseased segments, 344 segments
      were analysed. IRCS, proximal and middle ureter were completely opacified in 94%
      (81/86), 93% (80/86) and 77% (66/86) of cases, respectively. Median delay time
      was 15 min for complete opacification. The distal ureter was completely opacified
      in 37% (32/86) of cases and not opacified in 26% (22/86). Median delay time for
      complete opacification was 11 min with 25% and 75% percentiles of 10 and 16 min,
      respectively. At MDCTU, opacification of the IRCS, proximal and middle ureter was
      hardly sensitive to delay time. Delay times between 10 and 16 min were favourable
      in the distal ureter.

PMID- 16583217
TI  - Dynamic contrast-enhanced MRI for evaluation of cardiac tumors.

PMID- 16583218
TI  - DNA underreplication in intercalary heterochromatin regions in polytene
      chromosomes of Drosophila melanogaster correlates with the formation of partial
      chromosomal aberrations and ectopic pairing.
AB  - We studied the influence of the Suppressor of Underreplication (SuUR) gene
      expression on the intercalary heterochromatin (IH) regions of Drosophila
      melanogaster polytene chromosomes. We observed a strong positive correlation
      between increased SuUR expression, underreplication extent, amount of DNA
      truncation, and formation of ectopic contacts in IH regions. SuUR overexpression
      from heat shock-driven transgene results in the formation of partial chromosomal
      aberrations whose breakpoints map exclusively to the regions of intercalary and
      pericentric heterochromatin. It is important to note that all these effects are
      seen only if SuUR overexpression is induced during early stages of chromosome
      polytenization. Therefore, we developed the idea that ectopic pairing results
      from the joining of free DNA ends, which are formed as a consequence of
      underreplication.

PMID- 16583219
TI  - Dopamine affects cellular immune functions during polymicrobial sepsis.
AB  - OBJECTIVE: To determine whether infusion of dopamine modulates cellular immune
      functions and survival during systemic inflammation. DESIGN AND SETTING:
      Randomized animal study, university research laboratory, Level I trauma center.
      SUBJECTS: Male NMRI mice. INTERVENTIONS: Mice were subjected to laparotomy (sham
      intervention, LAP) or polymicrobial sepsis induced by cecal ligation and puncture
      (CLP). Mice in each of these conditions received either an intraperitoneal
      infusion of 0.9% saline (CLP/saline; LAP/saline) or an intraperitoneal infusion
      of dopamine (1.0 microg/kg/min i.p., CLP/DOP; LAP/DOP). Metabolic data and
      survival were monitored 24 h and 48 h after onset of sepsis, and animals were
      terminated 48 h after induction of sepsis to determine splenocyte apoptosis
      (Annexin V binding capacity), splenocyte proliferation (3H-Thymidine
      incorporation assay), splenocyte IL-2, IL-6 and IFN-gamma release (ELISA) and
      leukocyte distribution (WBC; CD3, CD4, CD8, B220, F4/80, NK1.1). MEASUREMENTS AND
      RESULTS: Infusion of dopamine in septic mice increased splenocyte apoptosis and
      decreased splenocyte proliferation and IL-2 release of septic mice. Furthermore,
      an inhibitory effect of dopamine infusion on splenocyte proliferation and the
      release of the TH1-cytokines IL-2 and IFN-gamma was observed in sham operated
      control mice. These effects were paralleled by a decreased survival of dopamine
      treated septic animals (47% vs. 67%). Treatment with DOP did not affect sepsis
      induced changes of leukocyte distribution. CONCLUSIONS: We conclude that dopamine
      is capable of modulating cellular immune functions in a murine model of sepsis.

PMID- 16583220
TI  - No good deed goes unpunished!

PMID- 16583221
TI  - Androgen receptors and gender-specific distribution of alkaline phosphatase in
      human thyroid cartilage.
AB  - The degree of mineralization in human thyroid cartilage is gender specific. Until
      now, laryngeal tissue was tested for sexual hormone receptors by the use of
      radiolabelled hormones only without exact localization of the receptors. In this
      study immediately frozen cartilage specimens from seven male and one female
      patient who underwent laryngectomy were used for immunolocalization of sexual
      hormone receptors. Additionally, serum sexual hormone levels were measured by
      means of radioimmunoassay. Alkaline phosphatase was localized
      enzymohistochemically in another cohort of six male and four female cartilage
      specimens from laryngectomies and autopsies. Chondrocytes in thyroid cartilage
      from both sexes reacted with antibodies to the androgen receptor. The low serum
      testosterone levels, which varied between 1.5 and 3.9 ng/ml, did not correlate
      with insufficient mineralization of thyroid cartilage in men (r=0.363, P=0.432).
      Chondrocytes did not react with antibodies to the estrogen receptor alpha and the
      progesterone receptor in both sexes. Expression of alkaline phosphatase started
      about the middle of the second decade. Some chondrocytes near the mineralization
      front were positive for androgen receptor and alkaline phosphatase, other
      chondrocytes were negative for both. Our results suggest the involvement of
      androgen receptor positive chondrocytes in thyroid cartilage mineralization,
      probably by a testosterone-linked stimulation of alkaline phosphatase.

PMID- 16583222
TI  - Comparison of age-dependent expression of aggrecan and ADAMTSs in mandibular
      condylar cartilage, tibial growth plate, and articular cartilage in rats.
AB  - A disintegrin and metalloproteinase with thrombospondin motif (adamalysin
      thrombospondins, ADAMTS) degrades aggrecan, one of the major extracellular matrix
      (ECM) components in cartilage. Mandibular condylar cartilage differs from primary
      cartilage, such as articular and growth plate cartilage, in its metabolism of
      ECM, proliferation, and differentiation. Mandibular condylar cartilage acts as
      both articular and growth plate cartilage in the growing period, while it remains
      as articular cartilage after growth. We hypothesized that functional and ECM
      differences between condylar and primary cartilages give rise to differences in
      gene expression patterns and levels of aggrecan and ADAMTS-1, -4, and -5 during
      growth and aging. We employed in situ hybridization and semiquantitative RT-PCR
      to identify mRNA expression for these molecules in condylar cartilage and primary
      cartilages during growth and aging. All of the ADAMTSs presented characteristic,
      age-dependent expression patterns and levels among the cartilages tested in this
      study. ADAMTS-5 mainly contributed to ECM metabolism in growth plate and condylar
      cartilage during growth. ADAMTS-1 and ADAMTS-4 may be involved in ECM turn over
      in articular cartilage. The results of the present study reveal that ECM
      metabolism and expression of related proteolytic enzymes in primary and secondary
      cartilages may be differentially regulated during growth and aging.

PMID- 16583223
TI  - [Neurophysiology of pruritus].
AB  - Neurophysiologic studies indicate that pruritus is a distinct sensation with its
      own neuronal pathways in the peripheral and central nervous system which are
      different from that of pain. Pruritus is a very disturbing sensation and most
      common skin-related symptom. Histamine was long considered to be the only
      mediator of pruritus. However, it has become evident that - besides histamine - a
      variety of neuromediators such as neurotrophins and neuropeptides as well as
      their receptors play an important role in pruritus. Neuromediators are produced
      by mast cells, keratinocytes and eosinophil granulocytes which are in close
      contact to sensory nerves. The discovery of these neurophysiological interactions
      opens new and promising therapeutic options for the treatment of pruritus.

PMID- 16583224
TI  - [Pruritus with systemic diseases].
AB  - Chronic itch is a frequent symptom not only associated with skin diseases. In a
      number of internal, neurological and psychiatric illnesses pruritus can be a
      prominent and distressing symptom. Diagnosis is frequently very cumbersome
      because pruritus in these diseases often does not cause any specific skin
      lesions. This report focuses on the most important internal disease entities
      causing pruritus and highlights the most successful diagnostic and therapeutic
      approaches.

PMID- 16583225
TI  - [Rational symptomatic therapy for chronic pruritus].
AB  - Chronic pruritus is a difficult-to-treat problem which accompanies many
      dermatologic and systemic diseases. Frequently, therapy is ineffective and
      prolongs the pruritus. Thus significant costs arise for the health system, which
      are clearly lowered by a rational therapy concept. Extensive knowledge about both
      topical and systemic therapy of pruritus has been acquired in recent years.
      Currently, new therapeutic approaches are available, which intervene in different
      pruritogenic mechanisms. Substances can block the cutaneous pruritus induction
      (e.g. antihistamines, leukotriene antagonists, cannabinoid agonists) or mediate
      central effects such as the inhibition of pruritus transmission via the spinal
      cord (e.g. naltrexone, gabapentin) or the suppression of the cerebral itch
      perception (e.g. antidepressants, neuroleptics). Usually combining several
      therapeutic principles is necessary in order to suppress chronic pruritus with
      lasting effect. The most effective approach is to gradually combine therapies,
      always considering both the medical and financial impacts.

PMID- 16583226
TI  - [Modern investigation with historical methods. Objective structured clinical
      examination (OSCE) of moulages].

PMID- 16583227
TI  - Enhancement of recombinant streptokinase production in Lactococcus lactis by
      suppression of acid tolerance response.
AB  - Lactococcus lactis is a potential host for production of recombinant proteins,
      especially of therapeutic importance. However, in glucose-grown cultures,
      lowering of pH due to accumulation of lactic acid and the concomitant induction
      of acid tolerance response (ATR) may affect the recombinant protein produced. In
      this work, we have analyzed the effect of culture pH and the associated ATR on
      production of recombinant streptokinase. Streptokinase gene was cloned and
      expressed as a secretory protein in L. lactis under the control of P170 promoter.
      It was found to undergo degradation to form inactive products leading to low
      productivity. The extent of degradation and productivity of streptokinase was
      greatly influenced by the development of ATR, which was dependent on the pH of
      the culture and initial phosphate concentration of the medium. It was found that
      high pH and high initial phosphate concentration leads to suppression of ATR and
      this results in at least 2.5-fold increase in streptokinase productivity and
      significant decrease in degradation of streptokinase.

PMID- 16583228
TI  - Isolation and characterization of a novel poly(vinyl alcohol)-degrading
      bacterium, Sphingopyxis sp. PVA3.
AB  - We have isolated a poly(vinyl alcohol) (PVA)-degrading bacterium from an
      activated sludge sample obtained from the drainage of a dyeing factory.
      Enrichment cultures were performed in media containing PVA as the sole or major
      carbon source. After several rounds of cultivation on liquid and solid media, we
      were able to isolate a single colony with PVA-degrading ability (strain PVA3).
      The bacterium could degrade PVA in the absence of symbionts or cofactors such as
      pyrroloquinoline quinone (PQQ). Over 90% of PVA, at an initial concentration of
      0.1%, was degraded within a 6-day cultivation. Degradation was confirmed by both
      iodometric methods and gel permeation chromatography. Examination of the PVA
      attached to the cells revealed a large increase in carbonyl groups, suggesting
      the oxidation of hydroxyl groups of the polymer on the surfaces of cells.
      Addition of PQQ to the culture medium did not enhance the growth and the PVA
      degrading rates of strain PVA3. Furthermore, we found that cells grown on PVA
      generated hydrogen peroxide upon the addition of PVA. The results strongly
      suggest that the initial oxidation of PVA is mediated via a PVA oxidase, and not
      a PQQ-dependent dehydrogenase. A biochemical and phylogenetic characterization of
      the bacterium was performed. The sequence of the 16S ribosomal RNA gene of the
      bacterium indicated a phylogenetic position of the strain within the genus
      Sphingopyxis, and the strain was therefore designated Sphingopyxis sp. PVA3.

PMID- 16583229
TI  - Plasmid-mediated degradation of 4-chloronitrobenzene by newly isolated
      Pseudomonas putida strain ZWL73.
AB  - A strain of Pseudomonas putida ZWL73 was isolated from soil contaminated with
      chloronitrobenzenes and identified by 16S rDNA sequencing. This bacterium
      released chloride and ammonia into the medium when grown on 4-chloronitrobenzene
      (4CNB) as the sole source of carbon, nitrogen and energy. A plasmid designated
      pZWL73 of approximately 100 kb in this strain was found to be responsible for
      4CNB degradation. This was based on the fact that the plasmid-cured strains
      showed 4CNB- phenotype and the 4CNB+ phenotype could be conjugally transferred.
      The cell-free extracts of strain ZWL73 exhibited chloronitrobenzene
      nitroreductase and 2-amino-5-chlorophenol 1, 6-dioxygenase (2A5CPDO) activities,
      but neither activity was found from that of the plasmid-cured strain. We have
      also cloned a 4.9-kb EcoRI fragment exhibiting 2A5CPDO activity. Sequencing
      results revealed beta-subunit (cnbCa) and alpha subunit (cnbCb) of a meta
      cleavage dioxygenase, which were subsequently expressed in E. coli with 2A5CPDO
      activity. The phylogenetic analysis suggested that 2A5CPDO may form a new
      subgroup in class III meta-cleavage dioxygenase with its close homologs.

PMID- 16583230
TI  - Reported adverse drug reactions during the use of inhaled steroids in children
      with asthma in the Netherlands.
AB  - OBJECTIVES: Inhaled corticosteroids (ICS) are widely used in the treatment of
      asthma. We studied the suspected adverse drug reactions (sADRs) reported during
      the use of ICS in the Netherlands. METHODS: In the Netherlands, health
      professionals and patients can report suspected ADRs to the Pharmacovigilance
      Centre Lareb. All reported sADRs on ICS were categorised and assessed as to
      whether these were likely to be associated with use of the steroid. Age and
      gender adjusted Reported Odds Ratios (RORs) and Naranjo Scores (NS) were computed
      for sADRs reported more than 3 times. RESULTS: Since 1984, sADRs of ICS were
      reported in 89 children (mean age 6 years), 48 (54%) were boys. Suspected drugs
      were fluticasone in 46 children (52%), budesonide in 21 (24%), and beclomethasone
      in 22 cases (24%). Psychiatric symptoms were reported in 19 children (21%; ROR
      3.8, NS 3.6), growth retardation in 6 children (7%; ROR 47.8, NS 3.0) and rashes
      in 6 cases (7%; ROR 0.7, NS 2.4). There were 7 reports (8%; ROR 2.1, NS 3.4)
      concerning abnormalities of the teeth, 4 reports of alopecia (4%; ROR 3.3, NS
      3.5), and 3 reports of hirsutism and hypertrichosis (NS 4.0). Non-fatal adrenal
      insufficiency was reported once. CONCLUSIONS: Alteration of behaviour was the
      most frequently reported sADR. There are more indications that alterations of
      behaviour could be a real sADR of ICS. Non-fatal adrenal insufficiency was the
      only reported possible life threatening sADR. The association of hypertrichosis
      and teeth abnormalities after ICS in children has not been reported in the
      literature before.

PMID- 16583231
TI  - Auditory response characteristics of the piebald odorous frog and their
      implications.
AB  - The piebald odorous frog (Odorrana schmackeri), the large odorous frog (Odorrana
      livida) and the concave-eared torrent frog (Amolops tormotus) are sympatric
      species living near the same torrent streams in the vicinity of Mt. Huangshan,
      China. A recent study demonstrated that A. tormotus can use sound signals
      involving ultrasonic components for communication in a noisy environment, and
      another sympatric species, O. livida, can also perceive ultrasonic sound. Here we
      report data on the hearing range of O. schmackeri by studying auditory evoked
      potentials and single-unit data from the torus semicircularis. This frog exhibits
      its two most sensitive peaks at 2 kHz and 3.5-4.0 kHz with thresholds <42 dB SPL,
      with an upper frequency limit of hearing at 8.5 kHz with threshold of 87 dB SPL.
      The upper limit is much lower than those of O. livida and A. tormotus, at 22 and
      34 kHz, respectively. It suggests that sympatric species may respond differently
      to similar environmental selection pressures sculpting auditory communication
      systems.

PMID- 16583232
TI  - Vibrating the food receivers: a direct way of signal transmission in stingless
      bees (Melipona seminigra).
AB  - An element common to the recruitment communication of eusocial bees (honey bees,
      stingless bees and bumble bees) are pulsed thorax vibrations generated by
      successful foragers within the nest. In stingless bees, foragers vibrate during
      the unloading of the collected food. In the present study on Melipona seminigra
      we demonstrate that during trophallactic contacts, the food receivers are
      directly vibrated by the foragers. As a consequence, both the temporal structure
      and the main frequency component of the forager's vibrations are directly passed
      on to the receiver. The vibrations are attenuated by about 17 dB on their way
      from the forager's thorax (velocity amplitude of the vibrations: approximately 70
      mm/s) to the receiver's thorax (approximately 10 mm/s), the main amount of
      attenuation (about 12 dB) occurring during transmission from the head of the
      forager to that of the receiver. Vibrations conducted through the substrate
      between the forager and food receiver are comparatively small with velocity
      amplitudes of 0.3 mm/s. Possible ways of perception and the advantages of
      vibration transmission by direct contact within the recruitment context are
      discussed.

PMID- 16583233
TI  - Effects of exercise training on pathological cardiac hypertrophy related gene
      expression and apoptosis.
AB  - This study determined whether exercise training prevents pathological hypertrophy
      in the left ventricle by modulation of myocardial and apoptosis-associated genes.
      We used spontaneously hypertensive rats (n=15, non-exercise SHR), exercise
      trained SHR (n=15, treadmill exercise for 12 weeks), and sedentary Wistar-Kyoto
      (WKY) rats (n=15). Exercise-trained SHR expressed adaptive changes such as
      reduced body weight, heart rate, blood pressures, left ventricle wall thickness,
      lipid profiles, and homocysteine level. The mRNA expression of angiotensin
      converting enzyme, endothelin-1, and brain natriuretic peptides in the heart was
      lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR,
      whereas mRNA expression of caveolin-3 and eNOS in the heart was higher. Bcl-2
      protein was higher in the exercise-trained SHR than in the WKY and the non
      exercise SHR. In contrast, Bax protein levels were lower in the exercise-trained
      SHR and in the WKY than in the non-exercise SHR. Furthermore, the levels of the
      active forms of caspase-3 (20 kDa) were lower in the exercise-trained SHR and in
      the WKY than in the non-exercise SHR. These findings suggest that exercise
      training prevents pathological hypertrophy in the left ventricle by modulation of
      myocardial genes and that it interferes with a signal transduction pathway of
      apoptosis secondary to the pathological cardiac hypertrophy.

PMID- 16583234
TI  - Bone metabolism in elite male rowers: adaptation to volume-extended training.
AB  - We examined the effect of 6-month volume-extended training on bone metabolism in
      elite male rowers. Twelve elite male rowers (20.8+/-3.0 years; 192.9+/-4.7 cm;
      91.9+/-5.3 kg; body fat 10.1+/-2.3%; VO2max 6.2+/-0.5 l min(-1)) participated in
      this study. Bone biochemical markers, hormones, bone mineral content (BMC), and
      bone mineral density (BMD) were assessed before and after training. Average
      weekly training volume was significantly higher (P<0.05) during the 6 months of
      heavy training compared to relative rest (11.6+/-0.4 h week(-1) vs. 16.8+/-0.6 h
      week(-1)), while intensity remained the same. At the end of training, only arm
      BMD was significantly increased by 5.7%. Osteocalcin (16.6%), insulin-like growth
      factor-1 (IGF-1) (20.2%) and the bioavailability IGF-1 index (17.9%) were
      significantly increased. Before heavy training, relationships were observed
      between the whole body BMD and growth hormone (r=0.64; P< or =0.02), lumbar spine
      BMD and 1.25(OH)2 vitamin D (r=0.69; P< or =0.04), arm BMD and testosterone
      (r=0.59; P< or =0.05), and arm BMD and adiponectin (r=0.59; P< or =0.05). No
      relationship was found between BMC or BMD and blood biochemical measures 6 months
      later (r=0.56; P> or =0.05). In addition, osteocalcin was related to IGF-1
      (r>0.58; P<0.048) and bioavailability IGF-1 index (r>0.59; P< or =0.055) before
      and after training. In summary, heavy training had a moderately favorable effect
      on BMD. Bone tissue at specific skeleton sites is sensitive to changes in
      training volume even in athletes with already high BMD values. Changes in BMD and
      bone formation may be caused by changes in specific hormones such as IGF-1 and
      adiponectin in male athletes.

PMID- 16583236
TI  - A novel cell division factor from tobacco 2B-13 cells that induced cell division
      in auxin-starved tobacco BY-2 cells.
AB  - Effects of auxin as plant hormones are widespread; in fact in almost all aspects
      of plant growth and development auxin plays a pivotal role. Although auxin is
      required for propagating cell division in plant cells, its effect upon cell
      division is least understood. If auxin is depleted from the culture medium,
      cultured cells cease to divide. It has been demonstrated in this context that the
      addition of auxin to auxin-starved nondividing tobacco BY-2 cells induced
      semisynchronous cell division. On the other hand, there are some cell lines,
      named habituated cells, that can grow without auxin. The cause and reason for the
      habituated cells have not been clarified. A habituated cell line named 2B-13 is
      derived from the tobacco BY-2 cell line, which has been most intensively studied
      among plant cell lines. When we tried to find the difference between two cell
      lines of BY-2 and 2B-13 cells, we found that the addition of culture filtrated
      from the auxin-habituated 2B-13 cells induced semisynchronous cell division in
      auxin-starved BY-2 cells. The cell division factor (CDF) that is responsible for
      inducing cell division in auxin-starved BY-2 cells was purified to near
      homogeneity by sequential passage through a hydroxyapatite column, a ConA
      Sepharose column and a Sephadex gel filtration column. The resulting purified
      fraction appeared as a single band of high molecular weight on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis gels by silver staining and was able
      to induce cell division in auxin-starved BY-2 cells. Identification of the
      protein by MALD-TOF-MS/MS revealed that it is structurally related to P
      glycoprotein from Gossypioides kirkii, which belongs to ATP-binding cassette
      (ABC)-transporters. The significance of CDF as a possible ABC-transporter is
      discussed in relationship to auxin-autotrophic growth and auxin-signaling
      pathway.

PMID- 16583235
TI  - Separable noradrenergic and dopaminergic regulation of prepulse inhibition in
      rats: implications for predictive validity and Tourette Syndrome.
AB  - INTRODUCTION: Startle inhibition by lead stimuli (prepulse inhibition, "PPI"),
      and the disruption of this process by dopamine agonists and N-methyl-D: 
      aspartate (NMDA) antagonists, are used in predictive models for antipsychotic
      development. PPI is also disrupted by the norepinephrine alpha-1 agonist,
      cirazoline, and the PPI-disruptive effects of the indirect dopamine agonist
      amphetamine are opposed by the norepinephrine reuptake inhibitor, desipramine.
      The hypothesis that PPI may be regulated by norepinephrine, or by interactions
      between dopamine and norepinephrine substrates, was tested in a series of
      experiments with the alpha-2 agonist, clonidine, which is used clinically to
      treat Tourette Syndrome (TS). MATERIALS AND METHODS: PPI was measured in male
      Sprague-Dawley rats after pretreatment with clonidine or the D2 antagonist
      haloperidol, and treatment with cirazoline, amphetamine, the D1/D2 agonist
      apomorphine, or the NMDA antagonist, phencyclidine. RESULTS: PPI was disrupted by
      cirazoline; this effect was prevented by clonidine but not haloperidol. PPI was
      disrupted by apomorphine; this effect was prevented by haloperidol but not
      clonidine. Clonidine also failed to oppose the PPI-disruptive effects of
      amphetamine and augmented the PPI-disruptive effects of phencyclidine. Over a
      range of prepulse intervals, clonidine enhanced PPI at short intervals and
      opposed the PPI-disruptive effects of cirazoline at long intervals. CONCLUSIONS:
      PPI is regulated by both norepinephrine and dopamine substrates that are
      neurochemically separable. The PPI-protective effects of clonidine suggest that
      the noradrenergic regulation of PPI may have utility for predicting therapeutic
      benefit in TS for drugs other than antipsychotics. Clonidine's failure to prevent
      the PPI-disruptive effects of apomorphine or phencyclidine further support the
      specificity of these PPI models for detecting drugs with antipsychotic
      properties.

PMID- 16583238
TI  - Gigantism in honeybees: Apis cerana queens reared in mixed-species colonies.
AB  - The development of animals depends on both genetic and environmental effects to a
      varying extent. Their relative influences can be evaluated in the social insects
      by raising the intracolonial diversity to an extreme in nests consisting of
      workers from more than one species. In this study, we studied the effects of
      mixed honeybee colonies of Apis mellifera and Apis cerana on the rearing of
      grafted queen larvae of A. cerana. A. mellifera sealed worker brood was
      introduced into A. cerana colonies and on emergence, the adults were accepted.
      Then, A. cerana larvae were grafted for queen rearing into two of these mixed
      species colonies. Similarly, A. cerana larvae and A. mellifera larvae were also
      grafted conspecifically as controls. The success rate of A. cerana queen rearing
      in the test colonies was 64.5%, surpassing all previous attempts at interspecific
      queen rearing. After emergence, all virgin queens obtained from the three groups
      (N=90) were measured morphometrically. The A. cerana queens from the mixed
      species colonies differed significantly in size and pigmentation from the A.
      cerana control queens and closely approximated the A. mellifera queens. It is
      inferred that these changes in the A. cerana queens reared in the mixed-species
      colonies can be attributed to feeding by heterospecific nurse bees and/or
      chemical differences in royal jelly. Our data show a strong impact of environment
      on the development of queens. The results further suggest that in honeybees the
      cues for brood recognition can be learned by heterospecific workers after
      eclosion, thereby providing a novel analogy to slave making in ants.

PMID- 16583237
TI  - Disulfide connectivity and reduction in pheromone-binding proteins of the gypsy
      moth, Lymantria dispar.
AB  - Males of the gypsy moth, Lymantria dispar, are attracted by a pheromone released
      by females. Pheromones are detected by olfactory neurons housed in specialized
      sensory hairs located on the antennae of the male moth. Once pheromone molecules
      enter the sensilla lymph, a highly abundant pheromone-binding protein (PBP)
      transports the molecule to the sensory neuron. The PBPs are members of the insect
      odorant-binding protein family, with six conserved cysteine residues. In this
      study, the disulfide bond connectivities of the pheromone-binding proteins PBP1
      and PBP2 from the gypsy moth were found to be cysteines 19-54, 50-109, and 97-118
      for PBP1, and cysteines 19-54, 50-110, and 97-119 for PBP2, as determined by
      cyanylation reactions and cyanogen bromide chemical cleavage. We have discovered
      that the second disulfide linkage is the most easily reduced of the three, and
      this same linkage is missing among four cysteine-containing insect odorant
      binding proteins (OBPs). We are the first to identify the unique steric and
      electronic properties of this second disulfide linkage.

PMID- 16583239
TI  - Primary colonization and breakdown of igneous rocks by endemic, succulent
      elephant trees (Pachycormus discolor) of the deserts in Baja California, Mexico.
AB  - Trees growing in rocks without soil are uncommon. In two arid regions in Baja
      California, Mexico, field surveys found large numbers of rock-colonizing elephant
      trees (Pachycormus discolor (Benth.) Coville ex Standl. (Mexican name: copalquin)
      growing in igneous rocks (granite and basalt) as primary colonizers without the
      benefit of soil or with a very small amount of soil generated by their own
      growth. Many adult trees broke large granite boulders and were capable of
      wedging, growing in, and colonizing rocks and cliffs made of ancient lava flows.
      This is the first record of a tree species, apart from the previously recorded
      cacti, capable of primary colonization of rocks and rock rubble in hot deserts.

PMID- 16583240
TI  - Effect of chronic treatment with perazine on lipopolysaccharide-induced
      interleukin-1 beta levels in the rat brain.
AB  - In the present study, we sought to determine whether chronic treatment with
      perazine alters lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta)
      levels in the following rat brain regions: the hypothalamus, frontal cortex,
      striatum and hippocampus. Male Wistar rats were administered perazine dimaleate
      (15 or 30 mg/kg/day) in drinking water for 21 days. On day 22, LPS was injected
      i.p. (125 microg/kg) 2 h before decapitation. Concentrations of perazine and its
      metabolites in plasma and brain was assessed by HPLC. The levels of IL-1 beta
      were determined using ELISA. Treatment with perazine (30 mg/kg/day) reduced LPS
      stimulated IL-1 beta levels in the hypothalamus, and a tendency to its decrease
      in the striatum and frontal cortex was observed. This in vivo study suggests for
      the first time that long-term oral administration of perazine modulates
      reactivity of cells producing IL-1 beta.

PMID- 16583241
TI  - Type IV Bartter syndrome: report of two new cases.
AB  - Bartter syndrome with sensorineural deafness (type IV Bartter syndrome) is a
      subtype of this tubular disease, and is due to mutations in the BSND gene. Out of
      a population of 92 patients with Bartter syndrome, five suffered from mild to
      severe hypoacusia and were selected for mutational screening. A homozygous
      mutation in the BSND gene was found in two female patients. The first patient was
      found to have a substitution in intron 1 donor splice site at position +5
      (c.420+5G>C), whereas the second patient has a homozygous 3G>A substitution
      leading to the loss of the start codon for the translation of the BSND mRNA. The
      clinical courses of these two patients were remarkable for severe polyhydramnios,
      massive renal salt and water wasting, severe neonatal hypotonia, poor growth and
      unresponsiveness to prostaglandin inhibitors. The diuretic responses to
      furosemide and to hydrochlorothiazide were tested under KCl supplementation in
      one patient. A lack of response to both drugs suggested that inhibition of NaCl
      reabsorption in type IV Bartter syndrome is not restricted to the thick ascending
      limb of Henle. In one patient, a combined therapy with indomethacin and captopril
      was needed to discontinue intravenous fluids and improve weight gain.

PMID- 16583242
TI  - Peritoneal dialysis in infants.
AB  - The need for maintenance dialysis for infants is rare, but peritoneal dialysis
      has been the modality of choice in cases of end-stage renal failure, for
      technical reasons. Problems include higher mortality rates and an inferior long
      term outcome compared with that in older children. Also, no internationally
      accepted guidelines exist for dialysis in infants. Many children on maintenance
      peritoneal dialysis in Finland have congenital nephrotic syndrome of the Finnish
      type (NPHS1), and dialysis is started during infancy. In this commentary we
      discuss our practice of performing peritoneal dialysis in infants and experiences
      gathered from the literature.

PMID- 16583243
TI  - Calcium and phosphate balance in adolescents on home nocturnal haemodialysis.
AB  - Studies in adults show superior serum phosphate and parathyroid hormone (PTH)
      control on slow nocturnal haemodialysis (NHD) compared with conventional
      haemodialysis. We studied the progress of four children aged 12, 13, 14 and 16
      years after they had been initiated on NHD. The follow-up period ranged from 6
      months to 20 months. Biochemical indices of bone metabolism were collected
      prospectively. All four children were initially dialysed against a 1.5 mmol/l
      calcium bath. In two patients, owing to biochemical hypocalcaemic episodes, the
      dialysate calcium concentration was increased to 1.75 mmol/l. One patient became
      hypercalcaemic and received calcitonin for bone pain secondary to osteoporosis
      and was dialysed against a 1.0 mmol/l calcium bath. Including an evaluation of
      dietary intake, all four patients had a net positive calcium balance, ranging
      from 5.1 mmol/m2 body surface area (BSA) per day to 24.3 mmol/m2 BSA per day. A
      significant reduction in the pre-dialysis phosphate level was observed in all
      four patients, such that none required dietary restrictions or phosphate binders,
      and dialysate phosphate supplements of 0.8-2.03 mmol/l were employed to prevent
      hypophosphataemia. The (CaxPO4) dropped below 4.4 mmol(2) l(-2) in all four
      patients. Concurrently, significant reductions in intact PTH levels were seen in
      all four patients, but the level dropped to below normal range in two. In our
      cohort of patients, NHD rapidly lowered plasma phosphate and PTH levels, and
      additional dialysate phosphate and possibly calcium may be necessary to prevent
      bone demineralisation due to chronic losses and to prevent oversuppression of
      PTH.

PMID- 16583244
TI  - Stature in children with chronic kidney disease: analysis of NAPRTCS database.
AB  - Despite recent advances in the management of children with chronic kidney disease
      (CKD), growth remains suboptimal. The purpose of this study was to evaluate
      factors associated with short stature in children with CKD. We evaluated the
      chronic renal failure registry of the North American Pediatric Renal Transplant
      Cooperative Studies (NAPRTCS) to determine the relations among primary diagnosis,
      age, race, residual renal function, acidosis, anemia, serum phosphorous, calcium,
      parathyroid hormone (PTH), albumin, and height at entry into the registry in
      children with CKD. A total of 5,615 patients were entered into the registry
      between January 1994 and January 2004. We found that older patients, those with
      glomerular filtration rate (GFR) >50 ml min(-1) 1.73 m(-2), black patients and
      patients with focal segmental glomerulosclerosis (FSGS) were at lower risk of
      being short at entry. Anemia (hematocrit below 33%) was an independent risk
      factor for short stature. Acidosis, serum phosphorous, calcium, albumin and PTH
      at registration were poor predictors of short stature. Age, race, primary
      diagnosis, and residual renal function were associated with short stature in
      children with CKD.

PMID- 16583245
TI  - Genetic susceptibility to hip arthroplasty failure--association with the RANK/OPG
      pathway.
AB  - The OPG/RANK/RANKL system has been implicated in the biological cascade of events
      initiated by particulate wear debris and bacterial infection resulting in
      periprosthetic bone loss around total hip arthroplasties (THA). Individual
      responses to such stimuli may be dictated by genetic variation caused by single
      nucleotide polymorphisms (SNPs). Case control study of the osteoprotegerin and
      RANK genes for possible association with deep sepsis or aseptic loosening. All
      patients were Caucasian and had had a cemented Charnley THA and polyethylene
      acetabular cup. Cases consisted of 91 patients with early aseptic loosening and
      71 patients with deep infection. Controls were 150 clinically and radiologically
      well-fixed THAs. DNA samples were genotyped using Taqman allelic discrimination.
      The A allele (p<0.001) and genotype A/A (p<0.001) for the OPG-163 SNP were
      associated with aseptic failure. Additionally, the RANK +575 (C/T SNP) T allele
      (p=0.004) and T/T genotype (p=0.008) frequencies were associated with aseptic
      failure. Comparing the septic group with the controls, the frequency of the A
      allele (p<0.001) and the genotype A/A (p<0.001) for the OPG-163 SNP were
      statistically significant. Aseptic loosening and deep infection of THA may be
      under the influence of susceptibility genes. SNP markers may serve as predictors
      of implant survival.

PMID- 16583246
TI  - Defective glycosylation of decorin and biglycan, altered collagen structure, and
      abnormal phenotype of the skin fibroblasts of an Ehlers-Danlos syndrome patient
      carrying the novel Arg270Cys substitution in galactosyltransferase I (beta4GalT
      7).
AB  - The Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue
      disorders affecting skin and joint function. Molecular defects in extracellular
      matrix proteins, including collagen (type I, III, and V) and tenascin X are
      associated with different forms of EDS. Compound heterozygous mutations in the
      B4GALT7 gene, resulting in aberrant glycosylation of the dermatan sulfate
      proteoglycan decorin, had been described in a single patient affected with the
      progeroid form of EDS. We have studied the molecular phenotype of decorin,
      biglycan, and collagen type I containing fibrils in skin fibroblasts of a patient
      carrying the novel homozygous C808T point mutation in the B4GALT7 gene, which
      causes an Arg270Cys substitution in beta4GalT-7. Compared to control fibroblasts,
      galactosyltransferase activity in beta4GalT-7(Arg270Cys) cells was approximately
      three times reduced over a temperature range of 25-41 degrees C. Pulse-chase
      experiments and confocal microscopy demonstrated that synthesis and secretion of
      decorin were normal in beta4GalT-7(Arg270Cys) cells. However, about 50% of
      decorin were synthesized as a protein core in addition to its proteoglycan form.
      Biglycan was found in a monoglycanated form in addition to its mature form.
      Glycosaminoglycan chains were of the dermatan/chondroitin sulfate type both in
      beta4GalT-7(Arg270Cys) and control cells, and epimerization was reduced for
      decorin and biglycan. Compared to control cells, beta4GalT-7(Arg270Cys) cells
      showed altered, highly spread or stretched phenotypes and decreased proliferation
      rates. At the ultrastructural level, an intracellular accumulation of multiple
      secondary lysosomes and degenerative vacuoles was seen in beta4GalT-7(Arg270Cys)
      cells. Furthermore, the collagen suprastructures were altered in the beta4GalT
      7(Arg270Cys) cells. The reduced beta4GalT-7 activity resulting in defective
      glycosylation of decorin and biglycan may be responsible for the complex
      molecular pathology in beta4GalT-7 deficient EDS patients, given the role of
      these proteoglycans in bone formation, collagen fibrillogenesis, and skeletal
      muscle development.

PMID- 16583247
TI  - Forensic mass screening using mtDNA.
AB  - At the forensic autopsy of a sexual murder victim, some trace hairs, possibly
      belonging to the perpetrator, were saved. Initially, the analysis of a pubic hair
      shaft only revealed the presence of the mitochondrial (mt) DNA haplotype profile
      consisting of the (CA)(6) allele and the complete hypervariable region 1 (HV1)
      and 2 (HV2) sequence. Later, typing of some further telogene trace hairs, which
      had been stored for several years, yielded a nuclear short tandem repeat (STR)
      profile. We used both the mtDNA haplotype and the STR profile to start a DNA mass
      screening project involving 2,335 male citizens of the relevant communities.
      MtDNA screening was carried out by using the CA repeat amplification in
      combination with an SNP typing procedure based on the restriction site analysis
      of amplified d-loop sequences. The aim of our paper is to put mass screening with
      mtDNA up for discussion.

PMID- 16583248
TI  - Applicability of Nanotrap Sg as a semen detection kit before male-specific DNA
      profiling in sexual assaults.
AB  - A commercially available semen detection kit, Nanotrap Sg, which employs a one
      step detection test based on immunochromatographic assay for the semenogelin
      protein, was evaluated for profiling male-specific DNA in sexual assault casework
      samples. While semen diluted with phosphate-buffered saline held and kept at 4
      degrees C for 1 week showed a relatively strong signal intensity with Nanotrap
      Sg, the signal intensity was decreased by dilution after storage at 4 degrees C
      or freezing and thawing repeated more than three times. The reproducibility of
      Nanotrap Sg was tested on a total of 174 sexual assault casework samples from
      three forensic laboratories using intra- and interassay and no variation was
      observed in the semenogelin (Sg) signal. The positive signal ratio was 12.6%
      higher for prostate-specific antigen immunochromatographic membrane tests than
      Nanotrap Sg. Although spermatozoa were not confirmed in 61 (35%) out of 174
      samples, Sg-positive signals could be detected from 41 (67%) of the 61 samples.
      Female genetic profiles could be observed in 95% of the samples, which tested
      negative for Sg on the Nanotrap Sg test, but no male genetic profiles could be
      observed. These results suggest that Nanotrap Sg can positively identify samples
      containing male DNA even in the absence of detectable intact spermatozoa.
      Further, Sg-positive signals identified samples for which male-specific DNA
      profiling could be performed, even if no sperm could be detected from the sample.
      The potential of Nanotrap Sg for identifying forensic samples with male-specific
      DNA was clearly demonstrated.

PMID- 16583249
TI  - Intravenous uterine leiomyomatosis with right heart extension: successful two
      stage surgical removal.
AB  - Intravenous leiomyomatosis is an uncommon nonmalignant tumor which originates
      from the smooth muscle cells and is usually confined to the pelvic venous system.
      Rarely, intracaval and intracardiac extension has been described: the literature
      includes only 100 cases with cardiac involvement. We report a case of a young
      woman with intravenous leiomyomatosis originating from the uterus and extending
      into the right atrium, successfully treated through a two-stage surgical
      approach.

PMID- 16583250
TI  - The relationship between gestational age and compliance in human umbilical vein
      and its possible application in vascular grafting.
AB  - The aim of this study was to provide a theoretical basis, using biomechanical
      properties, for the clinical application of human umbilical vein (HUV) as
      material for vascular grafting. This was a nonrandomized, non-controlled in vitro
      study. The experiment was conducted in the Laboratory of Medical Biomechanics,
      Yunyang Medical College. HUVs of 50 normal fetuses were collected on spontaneous
      miscarriage or labor with the pregnant women's permission by the Department of
      Obstetrics and Gynecology, Taihe Hospital, Shiyan, Hubei Province. Gestational
      aged ranged 24-42 weeks, and parturients were 20-30 years old. The pressure
      volume (P-V) relationship of HUV was measured on the biomechanical experiment
      stand for soft tissues, and then compliance was calculated. The P-V relationship
      of HUV corresponded to a parabolic curve. The compliance of HUV increased
      gradually with gestational age [24-27 weeks (2.22+/-0.34) x 10(-4) mL/(kPa * cm),
      28-32 weeks (3.65+/-0.46) x 10(-4) mL/(kPa * cm), 33-36 weeks (4.22+/-0.55) x 10(
      4) mL/(kPa * cm), 37 weeks (7.63+/-0.48) x 10(-4) mL/(kPa * cm), 38 weeks (8.32+/
      0.76) x 10(-4) mL/(kPa * cm)]. However, after 39 weeks of gestation, compliance
      decreased gradually with gestational age [39 weeks 7.61+/-0.46) x 10(-4) mL/(kPa
      * cm), 40 weeks (7.53+/-0.72) x 10(-4) mL/(kPa * cm), 41 weeks (4.13+/-0.35) x
      10(-4) mL/(kPa * cm), 42 weeks (2.25+/-0.62) x 10(-4) mL/(kPa * cm)]. The
      compliance of HUVs collected at 37-40 weeks of gestational age was similar. When
      the HUVs older than 42 weeks or under 28 weeks were compared, there was
      significant difference in their compliance (F=65.84-86.52, p<0.01). The results
      of the present study suggest that HUVs collected at 37-40 weeks of gestational
      age have good compliance, i.e., a good P-V relationship, and therefore may be a
      suitable material for vascular grafting. HUV is one of several graft materials
      that may be used when autogenous saphenous vein is absent or inadequate. HUV is
      very biocompatible and shows promise for use in orthopedic implants.

PMID- 16583251
TI  - Characterization of benign hepatic tumors arising in fatty liver with SonoVue and
      pulse inversion US.
AB  - BACKGROUND: We describe the spectrum of contrast-enhancement patterns of benign
      hepatic tumors arising in fatty liver on contrast-enhanced ultrasound (US).
      METHODS: Sixteen patients (12 women and four men) with 27 benign hepatic tumors
      (17 hemangiomas, eight focal nodular hyperplasias, and two hepatocellular
      adenomas) arising in fatty liver underwent baseline and pulse inversion US after
      administration of SonoVue. Two experienced radiologists evaluated baseline
      echogenicity and dynamic enhancement pattern of each lesion in comparison with
      adjacent liver parenchyma. RESULTS: After administration of SonoVue, in the
      arterial phase 13 of 17 hemangiomas showed peripheral globular enhancement and
      one showed a rim of peripheral enhancement, followed by progressive centripetal
      fill-in, which was complete in 10 of 14 cases and incomplete in four. Three of 18
      hemangiomas showed rapid and complete fill-in in the arterial phase. Eight of
      eight focal nodular hyperplasias became hyperechoic in comparison with adjacent
      liver parenchyma in the arterial phase and slightly hyperechoic or isoechoic in
      the portal venous and delayed phases. Both adenomas showed strong arterial
      contrast enhancement that became less intense in the portal venous and delayed
      phases. CONCLUSION: Contrast-enhanced US after administration of SonoVue enables
      depiction of typical contrast-enhancement patterns in most benign hepatic tumors
      arising in fatty liver, thus providing useful clues for characterization.

PMID- 16583252
TI  - Measurement and management of human-induced patterns of forest fragmentation: a
      case study.
AB  - In many tropical developing countries, the twin pressures of population and
      poverty are resulting in substantial fragmentation of forests, increasing the
      probability of extinction for many species, Forest fragmentation occurs when
      large contiguous forests are perforated by small holes or broken up into edges
      and smaller patches to form a nonforested matrix of open spaces. Thus, forest
      fragmentation refers not only to the area of forest cleared, but also to the
      pattern of this clearance, the resulting forest's spatial properties. Both
      characteristics are important for species survivability. Apart from opening up
      forests to many abiotic and biotic influences, fragmentation can affect species
      dispersal and migration through its effects on forest connectivity. Landscape
      ecology conceptualizes connectivity as a gradient of critical thresholds, ranging
      from the large intact forest to the small unconnected forest patch. This article
      reports results from a multiple-scale analysis of forest fragmentation in
      Jamaica's Cockpit Country, an area of once contiguous forest now under threat
      from human encroachment. Spatial forest data derived from classification of ETM+
      satellite imagery are used to measure fragmentation patterns representing various
      degrees of forest connectivity and density. The results suggest that, overall,
      81% of the region is in forest. However, fragmentation patterns also suggest that
      this forest is riven with extensive perforations indicative of an early stage in
      the decline of contiguity. The results provided by the spatial fragmentation
      model are a first step in the design of effective conservation and rehabilitation
      plans for the area. The article concludes with a discussion of possible
      multiscale management options for the region.

PMID- 16583253
TI  - Size distributions of soil particles adhered to children's hands.
AB  - The size distributions of the soil particles adhered to children's hands were
      preliminarily investigated and compared with a cutoff soil particle size recently
      specified in the official analytical method in Japan. To facilitate fieldworks
      involving child participants, we tested a methodology using a laser scattering
      particle size distribution analyzer and validated it for field applications. The
      laboratory experiments using this method showed finer soil particles tended to be
      adhered more efficiently to human hands. Meanwhile, our preliminary field survey
      revealed large variations in mass (mean 26.2 mg/hand, median 15.2 mg/hand, max
      162.5 mg/hand) and size distributions (particle mode diameter of 39 +/- 26
      microm) of the particles adhered to children's hands after various playing
      activities. Even though the ways the particles adhered were noticeably varied
      under actual playing situations, the adhered particles were consistently and
      considerably smaller than the 2-mm cutoff diameter defined by the Ministry of the
      Environment, Japan. Since soil contaminant concentrations are generally higher
      for finer soil particles, measurement of contaminant concentrations for the soil
      fraction including the non-adherent millimeter particles may underestimate the
      risk of direct soil contaminant intakes.

PMID- 16583254
TI  - Monitoring trace metal contaminants in green mussel, Perna viridis from the
      coastal waters of Karnataka, southwest coast of India.
AB  - The green mussel (Perna viridis) is widely distributed in the coastal waters of
      Asia and is used in mussel watch programmes for monitoring environmental
      contaminants throughout the region. Green mussels representing different size
      groups and habitats were sampled from their natural beds at 28 locations in the
      inshore waters of Karnataka (southwest coast of India) to analyze the tissue
      concentrations of Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn. Tissue concentrations of
      Cr, Cu, Fe, and Pb were significantly higher in smaller mussels than in the
      larger size group. Significantly higher concentrations of Cr, Cu, Fe, Mn, and Ni
      were observed in mussels sampled from intertidal beds when compared to mussels
      from the subtidal beds. The sampling sites were categorized into industrial sites
      (IS), urban sites (US), and nonurban sites (NS) based on principal component
      analysis of metal concentrations in mussel. Spatial variations in tissue
      concentrations of all metals were observed except for Zn. Generally, the levels
      of toxic trace metals like Pb, Cd, Ni, and Cr in the whole tissue of P. viridis
      were within safe limits throughout the coast of Karnataka. However, relatively
      high concentrations of Cd, Cr, and Pb were observed in the whole tissue of green
      mussels collected from the industrial sites (IS), which may be derived from a
      variety of anthropogenic activities.

PMID- 16583255
TI  - Effects of application methods of metam sodium and plastic covers on horizontal
      and vertical distributions of methyl isothiocyanate in bedded field plots.
AB  - This study was conducted to examine the effects of three application methods of
      metam sodium (broadcast, single irrigation drip tape delivery, and double
      irrigation drip tape delivery) and two plastic covers (polyethylene film and
      virtually impermeable film) on volatilization and on horizontal and vertical
      distributions of the biologically active product of metam sodium, methyl
      isothiocyanate (MITC), in field plots in a Florida sandy soil. Volatilization of
      MITC from field beds lasted for about 20 hours after completion of metam sodium
      application regardless of application methods. Virtually impermeable film (VIF)
      was a better barrier to reduce volatilization loss than polyethylene film (PE).
      Since water was not applied during broadcast application, MITC was mainly
      retained in the shallow soil layer (0- to 20-cm depth) and downward movement of
      MITC was limited to about 30 cm. Large values of standard deviation indicated
      that initial spatial distribution of MITC in the root zone (10- and 20-cm depths)
      of the two broadcast applied beds covered with PE or VIF was variable. Twice more
      water was delivered through the single drip tape than through individual tapes of
      double drip tape treatments during drip application of metam sodium. More water
      from the single drip tape likely facilitated downward movement of MITC to at
      least 60-cm depth, but MITC did not penetrate to this depth in the double drip
      tape beds. On the other hand, horizontal distribution of MITC in the root zone
      (10- and 20-cm depths) in the double drip tape beds was more uniform than in the
      single drip tape beds. More MITC was retained in the subsurface of the VIF
      covered beds regardless of application methods than in the PE-covered beds.

PMID- 16583256
TI  - Brominated indoles and phenols in marine sediment and water extracts from the
      north and baltic seas-concentrations and effects.
AB  - This work presents results from analytical as well as ecotoxicologic
      investigations of sediment and water samples from the North and Baltic Seas. A
      bioassay-directed procedure was used to investigate cause-effect relationships
      between observed effects in acute laboratory bioassays (luminescent bacteria
      assay with Vibrio fischeri and embryo test with Danio rerio) and analyte
      concentrations in extracted samples. Brominated phenols and indoles-including 4
      bromophenol; 2,4-dibromophenol; 4- and 6-bromoindole; 3,4-, 4,6-, and 3,6
      dibromoindole; and tribrominated compounds-were identified in partly remarkable
      concentrations (up to 40,000 ng g(-1) total organic carbon TOC for 4-bromophenol)
      in North Sea sediment samples and water samples (913 ng L(-1) 3,6-dibromoindole)
      from the German Bight. The toxicity of some of the identified brominated
      substances was low, with median effect concentration levels (EC(50)) ranging from
      0.08 to 21.7 mg/L for V. fischeri and 4.3 to 46.3 mg/L for D. rerio. Comparison
      of the concentrations of analytes with ECs showed a toxicity contribution of
      brominated phenols and indoles to overall toxicity of the fraction. In the case
      of one water sample from the German Bight, brominated phenols and indoles
      accounted for the observed toxicity. Brominated phenols and indoles, which are
      assumed to be of biogenic origin, have rarely been discussed so far in the
      context of ecotoxicologic effects in marine ecosystems.

PMID- 16583257
TI  - Physiological and reproductive effects of beta adrenergic receptor antagonists in
      Daphnia magna.
AB  - Although pharmaceuticals are increasingly found in surface waters, environmental
      levels of many of these compounds are not acutely toxic to model test organisms.
      Prior to conducting appropriate ecological risk assessments of pharmaceuticals,
      the mode of action-based biomarkers needs to be developed for non-target species.
      To evaluate toxicity of the beta-adrenergic blockers propranolol and metoprolol
      on non-target biota, we assessed standard ecotoxicological endpoints after 9 days
      of subchronic exposure in a transgenerational study with Daphnia magna. On day 9
      of exposure, the lowest observed effects concentration (LOEC) for growth were
      0.44 mg L(-1) for propranolol and 12 mg L(-1) for metoprolol. Total fecundity
      LOECs for the 9-day exposure were 0.11 mg L(-1) and 6 mg L(-1) for propranolol
      and metoprolol, respectively. In addition to typical ecotoxicological endpoints,
      we evaluated the utility of employing the physiological biomarkers of heart rate
      and metabolic rate following subchronic and acute exposures to propranolol and
      metoprolol. Propranolol and metoprolol LOECs for heart rate were 0.055 mg L(-1)
      and 3.1 mg L(-1), significantly lower than the LOECs for growth and reproduction.
      At these concentrations, heart rate was significantly lower than the control
      values for both compounds. Daphnia magna endpoint sensitivity to chronic
      propranolol and metoprolol exposure was mortality < growth < fecundity < heart
      rate. Second generation D. magna were less sensitive to both compounds. Responses
      of the physiological biomarkers heart rate and metabolic activity suggest that
      propranolol and metoprolol exerts sublethal toxicity to D. magna at lower
      concentrations than observed in the classical endpoints.

PMID- 16583258
TI  - Polychlorinated biphenyl concentrations, congener profiles, and ratios in the fat
      tissue, eggs, and plasma of snapping turtles (Chelydra s. serpentina) from the
      Ohio Basin of Lake Erie, USA.
AB  - Concentrations and profiles of polychlorinated biphenyls (PCBs) were determined
      in three tissues of adult snapping turtles (Chelydra serpentina serpentina) from
      six locations in the Ohio Basin of Lake Erie to characterize tissue variation and
      geographic trends. The locations included the Ohio Areas of Concern, i.e., the
      Ashtabula, Black, and Maumee Rivers; the Ottawa River near Toledo; and two
      reference sites. Mean total PCBs were greatest in turtles from the Ottawa River
      followed by the Maumee, Ashtabula, and Black Rivers. All three types of samples
      fat tissue (FT), eggs, and plasma-showed the same geographic trend in PCB levels.
      On a wet-weight basis, mean concentrations ranged from 2,148 to 18,669 ng/g in
      FT, from 183 to 3,683 ng/g in eggs, and from 18 to 201 ng/g in plasma. Across all
      sites, total PCB concentrations between the tissues were significantly correlated
      (0.001 < p < 0.005; Pearson correlation coefficient (r ( P )) was between 0.720
      and 0.954). Two distinctly different profiles with respect to relative congener
      and homologue concentrations were found among the sites. One that included four
      of the six sites examined was characterized by hexa-chlorobiphenyl (hexa-CB)
      dominance followed by hepta-CBs, with PCBs no. 138 + 163, 153 + 132 + 105, and
      180 being the most abundant congeners. The second profile, specific for turtles
      from the Ottawa River, was different from the first in that tetra-CBs were the
      most abundant congeners followed by hexa-CBs. Analysis of variance (ANOVA)
      indicated significant intertissue differences in the PCB homologue profiles,
      i.e., FT had a higher percentage of hepta-, octa-, and nona-CBs compared with
      eggs and plasma, whereas eggs showed a higher percentage of hexa-CBs. At any
      listed location, FT, eggs, and plasma had the same congener profile. An
      intertissue distribution of lipid-normalized individual congener concentrations
      examined by regression analyses revealed significant egg-FT, egg-plasma, and FT
      plasma relations for >40 congeners (0.001 < p < 0.05). The distribution ratios
      determined for these congeners from the slope of the regression lines averaged
      1.235 +/- 0.279, 0.430 +/- 0.170, and 0.387 +/- 0.115, respectively. The plasma
      wet weight-FT lipid-normalized concentration ratios for these congeners averaged
      0.012 +/- 0.006. Both egg-FT and plasma wet weight-FT lipid-normalized ratios
      regressed against log K(ow) showed significant decreases, with increasing log
      K(ow), indicating greater accumulation of highly chlorinated congeners in FT than
      in other compartments. The estimated 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic
      equivalents ranged from 0.007 ng/g at reference sites to 0.060 ng/g at
      contaminated sites and from 0.099 to 1.992 ng/g in plasma and eggs, respectively.
      In both plasma and eggs, coplanar-CBs were the major contributors to total toxic
      equivalents (TEQs). Eggs from all contaminated sites had TEQs that exceeded the
      lowest observed effect level TEQs proposed for bald eagle chicks, in addition to
      high SigmaPCB levels at some of these sites, especially the Ottawa and Maumee
      River sites, indicate potentially increased risk to turtles and possibly other
      wildlife species inhabiting these ecosystems. Significant correlations of total
      PCBs and individual congeners between FT, eggs, and plasma indicate that blood
      sampling can provide a good nonlethal measure of PCB exposure and can be used to
      monitor environmental contamination.

PMID- 16583259
TI  - Concentrations of polychlorinated biphenyl congeners in cultivated oysters
      (Crassostrea gigas) in western Taiwan.
AB  - Spatial and temporal variations of polychlorinated biphenyl (PCB) concentrations
      in cultivated oysters from five aquaculture areas along the western coast of
      Taiwan were investigated. Poor correlations between total PCB concentrations
      (ng/g dry weight [dw]) and physiologic parameters of oysters (shell length,
      width, thickness, and lipid content) were found. Total PCB concentrations ranged
      from 3.4 to 94 cng/g dw. The highest value was found in oysters from the Lu'ermen
      aquaculture area, which receives wastewater from a sodium hydroxide and
      pentachlorophenol factory. Furthermore, principal component analysis confirmed
      that the PCB congener pattern in this area was distinct from others and that two
      additional pollution sources might exist in the Tainan and Hsinchu areas. Oysters
      with PCB concentrations > 1 SD above the geometric mean were found mainly in
      Tainan (stations TN5 to TN9) with only one increased concentration in the Yunlin
      (station YL2) and Hsinchu (station HC4) aquaculture areas. Except for four
      confined stations, TN3 to TN6, where total PCB concentrations were higher (p =
      0.028) in the warmer (May and July) than in the colder season (November and
      March), seasonal variation of total PCB concentrations in oysters was not
      significant. Geometric mean and geometric mean plus 1 SD of total PCB
      concentrations in this study are lower than those in South Korea and the United
      States (Mussel Watch).

PMID- 16583260
TI  - The effect of pH on the uptake and toxicity of copper and zinc in a tropical
      freshwater alga (Chlorella sp.).
AB  - Copper and zinc toxicity to the freshwater alga Chlorella sp. was determined at a
      range of pH values (5.5-8.0) in a synthetic softwater (hardness 40-48 mg
      CaCO(3)/L). The effects of the metals on algal growth (cell division) rate were
      determined after 48-h exposure at pH 5.5, 6.0, 6.5, 7.0, 7.5, and 8.0. The
      toxicity of both metals was pH dependent. As pH decreased from 8.0 to 5.5, the
      copper concentration required to inhibit the algal growth rate by 50% (IC50)
      increased from 1.0 to 19 microg/L. For zinc, the IC50 increased from 52 to 2,700
      microg/L over the same pH range. Changes in solution speciation alone did not
      explain the increased toxicity observed as the pH increased. Modelled Cu(2+) and
      Zn(2+) concentrations decreased with increasing pH, whereas toxicity was observed
      to increase. Measurements of extracellular (cell-bound) metal concentrations
      support the biotic ligand model (BLM) theory of competition between protons
      (H(+)) and metals for binding sites at the algal cell surface. Higher
      extracellular metal concentrations were observed at high pH, indicating reduced
      competition. Independent of pH, both extracellular and intracellular copper were
      directly related to growth inhibition in Chlorella sp., whereas zinc toxicity was
      related to cell-bound zinc only. These findings suggest that the algal cell
      surface may be considered as the biotic ligand in further development of a
      chronic BLM with microalgae. Conditional binding constants (log K) were
      determined experimentally (using measured intracellular metal concentrations) and
      theoretically (using concentration-response curves) for copper and zinc for
      Chlorella sp. at selected pH values. Excellent agreement was found indicating the
      possibility of using concentration-response data to estimate conditional metal
      cell binding constants.

PMID- 16583261
TI  - Distribution of chloroplast DNA haplotypes in the contact zone of Fagus crenata
      in the southwest of Kanto District, Japan.
AB  - We have investigated cpDNA haplotype distribution in 24 populations of Fagus
      crenata in the southwest of Kanto District, Japan, and clarified the extent of
      intermixing of haplotypes in the contact zone by additional fine-scale analysis
      of two areas. Two cpDNA haplotypes belonging to different lineages were detected,
      and their distribution had geographical structure. Intermixed populations with
      the two haplotypes were limited to a narrow area. The geographical boundary
      between the haplotypes extended from Hakone to the west of the Kanto Mountains
      through the northern foot of Mt Fuji. No relationship was observed between the
      boundary location and the current topography of the southwest of Kanto District.

PMID- 16583262
TI  - Reproductive success and distance to conspecific adults in the sparsely
      distributed tree Kalopanax pictus.
AB  - To understand how a sparsely distributed species can maintain viable populations,
      and with a particular interest in distance-dependent reproductive success, we
      investigated the ovule survival and the factors that determine the survival for
      sparsely distributed Kalopanax pictus (Araliaceae) in a temperate forest
      landscape around the Ogawa Forest Reserve, central Japan. We found 154
      potentially mature trees (>20 cm diameter at breast height) in a 600-ha site. The
      year 2000 was a mass flowering year for K. pictus; 96.8% of the trees examined
      flowered in that year; however, this was less than half of the trees that
      flowered in other years. The flowers of K. pictus include protandrous
      inflorescences, which bloom on individual tress in midsummer when few other tree
      species bloom. We conducted pollination experiments with out-crossed, self
      pollinated, bagged, and control inflorescences. Results suggest that self
      pollination is limited, partially by low self-compatibility and partially by
      protandry. Ovule survival from the flower to the seed stages was not dependent on
      the temporal flowering density of conspecific adults. The flowering habit and
      presence of effective pollinators may allow K. pictus to avoid the negative
      effects of sparse distribution on pollination efficiency. However, ovule survival
      during the ovary development stage depended on infection by a species-specific
      fungus, Mycosphaerella acanthopanacis. The fungus damages leaves, and the
      infection intensity depends on the distance between conspecific K. pictus adults.
      Thus, an advantage of sparse distribution in K. pictus is disease avoidance,
      whereas its disadvantages are overcome by pollination efficiency.

PMID- 16583263
TI  - Capsaicin-induced inactivation of sensory neurons promotes a more aggressive gene
      expression phenotype in breast cancer cells.
AB  - Capsaicin-induced inactivation of sensory neurons has been reported to enhance
      metastasis of a murine breast cancer cell line, specifically enhancing myocardial
      metastases. Here we characterized changes in gene expression patterns in primary
      tumors which developed in capsaicin-treated vs. control mice. We identified a
      small cohort of genes (17) which all showed significant decreases in expression
      levels. All of the identified genes have been linked to cell growth,
      differentiation, and/or cancer progression. Three representative genes, Caspase-7
      (an executor of apoptosis), ADAM-10 (A Disintegrin and Metalloprotease), and Elk
      3 (a transcriptional repressor of the ternary factor subfamily of the Ets
      factors) were further investigated. All three showed dramatic downregulation at
      the protein level in primary tumors from capsaicin-treated animals compared with
      control (vehicle-treated) animals, and their expression was also lost in cell
      culture. Elk-3 and Caspase-7 were not expressed in vitro in cultured cell lines,
      suggesting that their expression was induced by the tumor microenvironment. Loss
      of Caspase-7 expression can be expected to result in loss of function of
      apoptotic pathways. At first glance, loss of ADAM-10 expression would be expected
      to result in decreased invasive capability, due to loss of matrix metalloprotease
      activity. However, just the opposite appears to be true. We found that ADAM-10
      actually hydrolyzes Substance P. Specifically ADAM-10 produces the same growth
      inhibitory products from Substance P (i.e., SP (1-7)) that Neprilysin does, so
      that loss of ADAM-10 expression actually results in loss of production of growth
      inhibitory peptides from Substance P. Similarly, ADAM-10 also efficiently
      hydrolyzes Calcitonin Gene-Related Peptide, which may act in concert with
      Substance P. Finally, overactivity of Ets transcriptional suppressor functions
      has been linked to inhibition of tumorigenesis (e.g., Erf and Mef), and in
      addition loss of Elk-3 expression might also be be linked to tumorigenesis via
      loss of its putative anti-inflammatory activities. There is anecdotal evidence in
      the literature to indicate that the rest of the down-regulated genes may also
      contribute to development of a more aggressive phenotype in this breast cancer
      model.

PMID- 16583264
TI  - Delay of adjuvant chemotherapy initiation following breast cancer surgery among
      elderly women.
AB  - BACKGROUND: Delay in the diagnosis of breast cancer is associated with worse
      stage distribution at diagnosis and decreased survival. However, the occurrence
      of delay in the delivery of adjuvant therapy and its impact on prognosis is not
      well understood. METHODS: To investigate the timeliness of initiation of adjuvant
      chemotherapy following surgery for breast cancer, we used data from the
      Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Among women
      > or = 65 years diagnosed between 1992 and 1999 with stages I-II breast cancer,
      we used linear regression and Cox proportional hazards models to investigate the
      time intervals between surgery and initiation of adjuvant chemotherapy, factors
      associated with delay, and the effect of delay on survival. RESULTS: Our sample
      consisted of 5003 women who received adjuvant chemotherapy. Of these, 47%
      initiated chemotherapy within 1 month, 37% between 1 and 2 months, 6% between 2
      and 3 months and 10% >3 months (delay) following surgery. Delay was associated
      with increasing age, residing in a rural location, being unmarried, earlier tumor
      stage, hormone receptor positivity, mastectomy, and non-receipt of radiation
      therapy. Survival did not differ among patients who initiated chemotherapy within
      1, 2, or 3 months after surgery. Delay beyond 3 months was, however, associated
      with increased disease-specific mortality (HR 1.69; 95% CI 1.31-2.19) and overall
      mortality (HR 1.46; 95% CI 1.21-1.75). CONCLUSIONS: Among older patients,
      moderate delays in the receipt of adjuvant chemotherapy occur frequently, but
      long delays (>3 months) are uncommon. While early initiation of therapy is no
      benefit, significant delays are associated with increased mortality. Whether this
      reflects the medical impact of the delay of chemotherapy or factors associated
      with delay is unclear, but until this is clarified, patients should be encouraged
      to initiate treatment without significant delay.

PMID- 16583265
TI  - Malignant transformation eight years after removal of a benign epidermoid cyst: a
      case report.
AB  - Malignant transformation of benign epidermoid cysts is rare and their prognosis
      remains poor. A 56-year-old woman presented with left facial hypoesthesia and
      photophobia in the left eye. She had undergone removal of a benign epidermoid
      cyst in the cerebellopontine angle 8 years previously. Magnetic resonance imaging
      of the brain revealed a cystic lesion in the left cerebellopontine angle. The
      cyst wall was enhanced by gadolinium-DTPA. She underwent removal again and the
      histopathologic diagnosis was squamous cell carcinoma. Gamma knife radiosurgery
      was performed on the remnant lesion with a marginal dose of 15 Gy. The tumor
      shrank rapidly for 2 months after radiosurgery, but recurred 9 months later. She
      underwent radiosurgery again with a marginal dose of 12 Gy. A gradual increase in
      the size of the enhanced lesion was seen during the 4-month follow-up period
      subsequent to the second radiosurgery. Careful observation, employing serial
      magnetic resonance images, is necessary for incompletely resected epidermoid
      cysts because intervals before malignant transformation reportedly range from 3
      months to 33 years. Newly identified contrast enhancement strongly indicates
      malignant change in epidermoid cysts. Gamma knife radiosurgery may be useful for
      short-term control of intracranial squamous cell carcinomas, but long-term
      effects are presently unknown.

PMID- 16583268
TI  - Confronting "hereditary" disease: eugenic attempts to eliminate tuberculosis in
      progressive era America.
AB  - Tuberculosis was clearly one of the most predominant diseases of the early
      twentieth century. At this time, Americans involved in the eugenics movement grew
      increasingly interested in methods to prevent this disease's potential hereditary
      spread. To do so, as this essay examines, eugenicists' attempted to shift the
      accepted view that tuberculosis arose from infection and contagion to a view of
      its heritable nature. The methods that they employed to better understand the
      propagation and control of tuberculosis are also discussed. Finally, the essay
      explores the interpretative analyses of data that the Eugenics Record Office used
      in an attempt to convince contemporaries of the hereditary transmission of
      tuberculosis.

PMID- 16583266
TI  - Pharmacodynamics of antiretroviral agents in HIV-1 infected patients: using viral
      dynamic models that incorporate drug susceptibility and adherence.
AB  - We developed a novel HIV-1 dynamic model with consideration of pharmacokinetics,
      drug adherence and drug susceptibility to link plasma drug concentration to the
      long-term changes in HIV-1 RNA observation after initiation of therapy. A
      Bayesian approach is proposed to fit this model to clinical data from ACTG A5055,
      a study of two dosage regimens of indinavir (IDV) with ritonavir (RTV) in
      subjects failing their first protease inhibitor treatment. The HIV RNA testing
      was completed at days 0, 7, 14, 28, 56, 84, 112, 140, and 168. An intensive
      pharmacokinetic (PK) evaluation was performed on day 14 and multiple trough
      concentrations were subsequently collected. Pill counts were used to monitor
      adherence. IC(50) for IDV and RTV were determined at baseline and at virologic
      failure. Viral dynamic model fitting residuals were used to assess the
      significance of covariate effects on long-term virologic response. As univariate
      predictors, none of the four PK parameters C(trough), C(12 hour), C(max), and AUC
      was significantly related to virologic response (p > 0.05). By including drug
      susceptibility (IC(50)), or IC(50) and adherence measured by pill counts
      together, C(trough), C(12 hour), C(max) and AUC were each significantly
      correlated to long-term virologic response (p = 0.0055,0.0002,0.0136,0.0002 with
      IC(50) and adherence measured by pill counts considered). The IC(50) and
      adherence measured by pill counts alone were not related to the virologic
      response. In predicting virologic response adherence measured by pill counts did
      not provide any additional information to PK parameters (p = 0.064), to drug
      susceptibility IC(50) (p = 0.086), and to their combination (p = 0.22). Simple
      regression approaches did not detect any significant pharmacodynamic (PD)
      relationships. Any single factor of PK, adherence measured by pill counts and
      drug susceptibility did not contribute to long-term virologic response. But their
      combinations in viral dynamic modeling significantly predicted virologic
      response. The HIV dynamic modeling can appropriately capture complicated
      nonlinear relationships and interactions among multiple covariates.

PMID- 16583269
TI  - Simulated interactions between a Class III antiarrhythmic drug and a figure 8
      reentry.
AB  - Ventricular Fibrillation is responsible for a majority of sudden cardiac death,
      but little is known about how ventricular tachycardia (VT) degenerates into
      ventricular fibrillation. Several clinical studies focused only on preventing VT
      with a class III antiarrhythmic drug resulted in many deaths. Our simulations
      investigate the interactions between an antiarrhythmic drug likely to suppress a
      VT and a Figure 8 reentry. A parameter AAR is introduced to increase the action
      potential duration and therefore simulate various Class III drugs. Simulations
      are ran under several conditions (phases of the reentry, values of AAR,
      durations). They show that a VT can be suppressed whatever the phase of the
      reentry but it strongly depends on the duration of the effect. It confirms that a
      drug which can suppress a reentry can also worsen it. It also shows a great
      variety of activation patterns and thus the complexity of antiarrhythmic drugs
      effects. Simulations also demonstrate that suppressing VT is an increasing
      function of AAR.

PMID- 16583267
TI  - Elevation in plasma Abeta42 in geriatric depression: a pilot study.
AB  - Elevated plasma amyloid beta 1-42 (Abeta42) level has been linked to increased
      risk for incident AD in cognitively-intact elderly. However, plasma Abeta levels
      in individuals with late-life depression (LLMD), especially those with a late age
      of onset of first depressive episode, who are at a particularly increased risk
      for Alzheimer's disease, have not been studied. We compared plasma Abeta in 47
      elderly with LLMD with 35 controls and examined its relationships to age of onset
      of first depressive episode, antidepressant treatment (paroxetine or
      nortriptyline), and indices of platelet activation (platelet factor 4 and beta
      thromboglobulin) and brain abnormalities. Results indicated that plasma Abeta42
      levels and the Abeta42/40 ratio were elevated in the LLMD group relative to
      controls in the overall group analyses and in the age- and gender-matched groups.
      MRI data indicated that higher Abeta42/40 ratio was associated with greater
      severity of total white matter hyperintensity burden in LLMD. Plasma Abeta levels
      in LLMD were not influenced by age of onset of first depressive episode or
      antidepressant treatment and were not related to indices of platelet activation.
      Our preliminary results suggest that increased plasma Abeta42 and Abeta42/40
      ratio are present in geriatric depression, and future studies should be done to
      confirm these findings and to determine their relationship to cognitive decline
      and brain abnormalities associated with LLMD.

PMID- 16583270
TI  - An integrative model of the self-sustained oscillating contractions of cardiac
      myocytes.
AB  - Computational cell models appear as necessary tools for handling the complexity
      of intracellular cell dynamics, especially calcium dynamics. However, while
      oscillating intracellular calcium oscillations are well documented and modelled,
      a simple enough virtual cell taking into account the mechano-chemical coupling
      between calcium oscillations and cell mechanical properties is still lacking.
      Considering the spontaneous periodic contraction of isolated cardiac myocytes, we
      propose here a virtual cardiac cell model in which the cellular contraction is
      modelled using an hyperelastic description of the cell mechanical behaviour.
      According to the experimental data, the oscillating cytosolic calcium
      concentrations trigger the spatio-temporal variation of the anisotropic
      intracellular stresses. The finite element simulations of the virtual cell
      deformations are compared to the self-sustained contractions of isolated rat
      cardiomyocytes recorded by time-lapse video-microscopy.

PMID- 16583272
TI  - Hypercomplexity.
AB  - What is biological complexity? How many sorts exist? Are there levels of
      complexity? How are they related to one another? How is complexity related to the
      emergence of new phenotypes? To try to get to grips with these questions, we
      consider the archetype of a complex biological system, Escherichia coli. We take
      the position that E. coli has been selected to survive adverse conditions and to
      grow in favourable ones and that many other complex systems undergo similar
      selection. We invoke the concept of hyperstructures which constitute a level of
      organisation intermediate between macromolecules and cells. We also invoke a new
      concept, competitive coherence, to describe how phenotypes are created by a
      competition between maintaining a consistent story over time and creating a
      response that is coherent with respect to both internal and external conditions.
      We suggest how these concepts lead to parameters suitable for describing the rich
      form of complexity termed hypercomplexity and we propose a relationship between
      competitive coherence and emergence.

PMID- 16583271
TI  - A bond graph model of the cardiovascular system.
AB  - The study of the autonomic nervous system (ANS) function has shown to provide
      useful indicators for risk stratification and early detection on a variety of
      cardiovascular pathologies. However, data gathered during different tests of the
      ANS are difficult to analyse, mainly due to the complex mechanisms involved in
      the autonomic regulation of the cardiovascular system (CVS). Although model-based
      analysis of ANS data has been already proposed as a way to cope with this
      complexity, only a few models coupling the main elements involved have been
      presented in the literature. In this paper, a new model of the CVS, representing
      the ventricles, the circulatory system and the regulation of the CVS activity by
      the ANS, is presented. The models of the vascular system and the ventricular
      activity have been developed using the Bond Graph formalism, as it proposes a
      unified representation for all energetic domains, facilitating the integration of
      mechanic and hydraulic phenomena. In order to take into account the electro
      mechanical behaviour of both ventricles, an electrophysiologic model of the
      cardiac action potential, represented by a set of ordinary differential
      equations, has been integrated. The short-term ANS regulation of heart rate,
      cardiac contractility and peripheral vasoconstriction is represented by means of
      continuous transfer functions. These models, represented in different continuous
      formalisms, are coupled by using a multi-formalism simulation library. Results
      are presented for two different autonomic tests, namely the Tilt Test and the
      Valsalva Manoeuvre, by comparing real and simulated signals.

PMID- 16583273
TI  - Effects of density dependent migrations on the dynamics of a predator prey model.
AB  - We study the effects of density dependent migrations on the stability of a
      predator-prey model in a patchy environment which is composed with two sites
      connected by migration. The two patches are different. On the first patch, preys
      can find resource but can be captured by predators. The second patch is a refuge
      for the prey and thus predators do not have access to this patch. We assume a
      repulsive effect of predator on prey on the resource patch. Therefore, when the
      predator density is large on that patch, preys are more likely to leave it to
      return to the refuge. We consider two models. In the first model, preys leave the
      refuge to go to the resource patch at constant migration rates. In the second
      model, preys are assumed to be in competition for the resource and leave the
      refuge to the resource patch according to the prey density. We assume two
      different time scales, a fast time scale for migration and a slow time scale for
      population growth, mortality and predation. We take advantage of the two time
      scales to apply aggregation of variables methods and to obtain a reduced model
      governing the total prey and predator densities. In the case of the first model,
      we show that the repulsive effect of predator on prey has a stabilizing effect on
      the predator-prey community. In the case of the second model, we show that there
      exists a window for the prey proportion on the resource patch to ensure
      stability.

PMID- 16583274
TI  - Structural stability of a stage structured model of fish: the case of the anchovy
      (Engraulis encrasicolus L.) in the Bay of Biscay.
AB  - A study of stage structured model of fish population is presented. This model
      focuse on the anchovy population in the Bay of Biscay (Engraulis encrasicolus L.)
      is presented. The method of study is based on an intermediate complexity
      mathematical model, taking into account the spatialisation, the environmental
      conditions and the stage-structure of the fishes. First, to test the model, we
      show mathematical properties, such as unicity of the solution of structural
      stability. Then we provide numerical simulations, to validate the model and to
      test the dynamics according to the variations of the parameters.

PMID- 16583275
TI  - Global production increased by spatial heterogeneity in a population dynamics
      model.
AB  - Spatial and temporal heterogeneity are often described as important factors
      having a strong impact on biodiversity. The effect of heterogeneity is in most
      cases analyzed by the response of biotic interactions such as competition of
      predation. It may also modify intrinsic population properties such as growth
      rate. Most of the studies are theoretic since it is often difficult to manipulate
      spatial heterogeneity in practice. Despite the large number of studies dealing
      with this topics, it is still difficult to understand how the heterogeneity
      affects populations dynamics. On the basis of a very simple model, this paper
      aims to explicitly provide a simple mechanism which can explain why spatial
      heterogeneity may be a favorable factor for production. We consider a two patch
      model and a logistic growth is assumed on each patch. A general condition on the
      migration rates and the local subpopulation growth rates is provided under which
      the total carrying capacity is higher than the sum of the local carrying
      capacities, which is not intuitive. As we illustrate, this result is robust under
      stochastic perturbations.

PMID- 16583276
TI  - Nutrient fluxes toward phytoplankton: is it useful to consider turbulence
      intermittency?
AB  - The Influence of turbulence on nutrient fluxes towards phytoplankton cells has
      been previously estimated, but those studies did not take into account the
      intermittent nature of turbulent processes. This has been investigated here
      comparing the nutrient fluxes obtained using both mean and instantaneous
      turbulent energy dissipation rates. This approach shows that the size of cell
      potentially influenced by turbulence is lower than previously indicated, and that
      the spectral average estimate of the turbulence effect overestimates the flux.
      The capacity of cell to use such intermittent flux is then discussed.

PMID- 16583277
TI  - Hysteresis dynamics, bursting oscillations and evolution to chaotic regimes.
AB  - This article describes new aspects of hysteresis dynamics which have been
      uncovered through computer experiments. There are several motivations to be
      interested in fast-slow dynamics. For instance, many physiological or biological
      systems display different time scales. The bursting oscillations which can be
      observed in neurons, beta-cells of the pancreas and population dynamics are
      essentially studied via bifurcation theory and analysis of fast-slow systems
      (Keener and Sneyd, 1998; Rinzel, 1987). Hysteresis is a possible mechanism to
      generate bursting oscillations. A first part of this article presents the
      computer techniques (the dotted-phase portrait, the bifurcation of the fast
      dynamics and the wave form) we have used to represent several patterns specific
      to hysteresis dynamics. This framework yields a natural generalization to the
      notion of bursting oscillations where, for instance, the active phase is chaotic
      and alternates with a quiescent phase. In a second part of the article, we
      emphasize the evolution to chaos which is often associated with bursting
      oscillations on the specific example of the Hindmarsh-Rose system. This evolution
      to chaos has already been studied with classical tools of dynamical systems but
      we give here numerical evidence on hysteresis dynamics and on some aspects of the
      wave form. The analytical proofs will be given elsewhere.

PMID- 16583278
TI  - Generalised biological function.
AB  - A physiological function can be described as a cycle based on a cusp bifurcation
      set in catastrophe theory. This cycle involves four phases that are successively
      developed along a functional potential, which is used to perform a given
      physiological act. The work we present is firstly based on a detailed study of
      the global function of vision, which covers a vast field extending from the
      molecular to cerebral scale. We then present other examples of generalised
      functions by expanding the frame of reference, from the scale of an organ to the
      scale of a whole organism with predation function, and to the scale of a social
      group with crisis management. We observed that the criteria remain the same,
      whether the function is considered on the scale of a cell membrane or a group of
      individuals organised into a cohort. Moreover, a so-called generalised function
      can be broken down into simpler sub-functions, each phase of the initial function
      containing the physiological act of each sub-function. It seems thus that a
      fractal extension may characterise the four-cusp spiral. This spiral is
      increasingly large as the types of sub-functions are multiplied. In functions
      relative to sociological science, such as crisis management, which are not
      natural but built and designed by humans, close attention must be paid to
      following the rules of these generalised biological functions.

PMID- 16583279
TI  - The joy of science.

PMID- 16583280
TI  - ROC and loss function analysis in sequential testing.
AB  - Sequential testing is applied to reduce costs in SP-based tests (OSCEs).
      Initially, all candidates take a screening test consisting of a part of the OSCE.
      Candidates who fail the screen sit the complete test, whereas those who pass the
      screen are qualified as a pass of the complete test. The procedure may result in
      a reduction of testing resources, but at the cost of false positives (candidates
      who pass the screen but would fail the complete test). In a diagnostic test an
      optimum cutpoint is obtained by minimizing the weighted sum of false negatives
      and false positives using Receiver Operator Characteristic (ROC) analysis.
      However, in the sequential procedure there are no false negatives, because the
      result of the complete test is considered the final outcome. Several authors
      ignored this difference and applied classic ROC analysis to a sequential test.
      Earlier, we doubted the validity of the procedure and proposed to set the
      cutpoint by minimizing the loss, defined as the weighted sum of the screen
      negatives and the false positives. Recently, Regehr and Colliver (2003) argued
      that under certain theoretically derived conditions the use of the loss formula
      in sequential testing is functionally identical to using classic ROC analysis.
      The current study shows (a) the conclusion of Regehr and Colliver is based on
      assumptions that can be challenged, and (b) ROC analysis indeed can be used in
      sequential testing, but only if the procedure is modified according to the
      results of a corresponding loss function analysis.

PMID- 16583281
TI  - Measuring what medical students think about complementary and alternative
      medicine (CAM): a pilot study of the complementary and alternative medicine
      survey.
AB  - With increasing national and international support for the development of
      Complementary and Alternative Medicine (CAM) curricula in American medical
      schools, it is essential to measure what learners know and believe about CAM in
      order to assess outcomes of new teaching efforts. This paper describes the
      development and initial results of a survey designed for those purposes. The
      survey is constructed so that earlier single-institution studies of students'
      attitudes toward CAM topics, preferred ways of learning about CAM, and students'
      use of CAM therapies for self-care might be replicated and extended. A pilot test
      of the Complementary and Alternative Medicine ( CAM) Survey was conducted with
      third-year medical students at the University of Texas Medical Branch. Validity
      and reliability studies of the survey were conducted. Findings were compared to
      those of previously published studies. Interpretable subscales were constructed
      from survey questions. Students' attitudes toward CAM-related topics were
      generally favorable. More students were familiar with biological-based therapies
      than with other CAM therapies. The majority of respondents listed lectures as
      their preferred way to learn about CAM. Respondents' own CAM use varied; minority
      and economically-disadvantaged students were more likely to use CAM therapies
      than other students. The survey is a promising assessment of student attitudes
      toward and knowledge of CAM therapies.

PMID- 16583282
TI  - A randomized controlled trial of simulation-based teaching versus traditional
      instruction in medicine: a pilot study among clinical medical students.
AB  - OBJECTIVE: To compare simulator-based teaching with traditional instruction among
      clinical medical students. METHODS: Randomized controlled trial with written pre
      post testing. Third-year medical students (n = 38) received either a myocardial
      infarction (MI) simulation followed by a reactive airways disease (RAD) lecture,
      or a RAD simulation followed by an MI lecture. RESULTS: Mean pre-post test score
      improvement was seen across teaching modalities (overall change score
      [simulation] = 8.8 [95% CI = 2.3-15.3], pretest [62.7]; change score [lecture] =
      11.3 [95% CI = 5.7-16.9], pretest [59.7]). However, no significant differences
      were observed between simulator-based teaching and lecture, in either subject
      domain. CONCLUSIONS: After a single instructional session for clinical medical
      students, differences between simulator-based teaching and lecture could not be
      established by the written test protocols used in this pilot. Future studies
      should consider the effects of iterative exposure assessed by clinical
      performance measures across multiple centers.

PMID- 16583283
TI  - Determining the need for simulated training of invasive procedures.
AB  - Unlike the airline industry, where pilots first learn to fly on simulators before
      navigating planes, physicians practice invasive procedures on real patients. To
      determine the need for the simulated training of invasive procedures prior to
      working on patients, we studied the views of physicians-in-training. Five hundred
      medical students, residents, and fellows at Harvard Medical School were asked if
      there was a problem with the way medical procedures presently are learned in
      health care. Next, they were surveyed to inquire whether using a simulator would
      be beneficial. Finally, they were asked what specific procedures would be most
      suitable for virtual training. The effects of respondent gender, level of
      training, specialty, and previous experience using simulation on survey results
      was tested using Student t-tests. One hundred and fifty-eight trainees responded
      that they were uncomfortable learning to perform invasive procedures on patients.
      Students and physicians were very interested in obtaining simulated training
      prior to practicing on patients. The more complicated the procedure, the greater
      the feeling that it should be simulated prior to attempting it on patients.
      Respondents most preferred that simulation be used to teach chest tube placement.
      Respondent gender, specialty, level of training, and prior simulation experience
      did not affect survey results (p > 0.05). Simulation should be incorporated into
      the education of medical students and residents as a tool to practice invasive
      procedures prior to working on patients.

PMID- 16583284
TI  - Relationships between self-assessment skills, test performance, and demographic
      variables in psychiatry residents.
AB  - Some researchers have seen the capacity for self-assessment in trainees as a
      special skill, and some reports have concluded that this skill is positively and
      crucially correlated with academic competence. Thus, it is believed that those
      trainees who are most deficient in knowledge are least likely to be aware of
      their limitations. Other researchers have emphasized the impact of statistical
      regression and other technical considerations in the studies, which have led to
      these conclusions. Our study used a relative-ranking design to measure the
      accuracy of self-assessments of both strengths and weaknesses in psychiatry
      residents. We analyzed the relationships between indices of self-assessment
      accuracy and other resident characteristics, particularly current academic
      strength as measured by a standard test of psychiatric knowledge. A total of 56
      residents in two general psychiatry programs evaluated their performance on the
      Psychiatry Resident in Training Examination by estimating the rank order of their
      scores in the 11 psychiatry subject areas. For each resident, actual examination
      results were then used to generate measures of the accuracy of the identification
      of strengths and weaknesses. Residents' identifications of their strengths and
      weaknesses were significantly more accurate than chance levels. Strengths and
      weaknesses were identified with roughly equal proficiency, and accuracy in these
      assessments was not correlated to any of the following variables: academic
      competence as measured by examination raw scores, postgraduate year, gender,
      international vs. American medical education, program membership, or age. Our
      results do not support the hypothesis that trainees who show the least academic
      mastery also make the most inaccurate self-assessments. In addition, we found no
      resident characteristics that accounted for variation in self-assessment
      accuracy.

PMID- 16583285
TI  - Use of a committee review process to improve the quality of course examinations.
AB  - PURPOSE: In conjunction with curricular changes, a process to develop integrated
      examinations was implemented. Pre-established guidelines were provided favoring
      vignettes, clinically relevant material, and application of knowledge rather than
      simple recall. Questions were read aloud in a committee including all course
      directors, and a reviewer with National Board of Medical Examiners (NBME) item
      writing and review experience. This study examines the effectiveness of this
      process to improve the quality of in-house examinations. METHODS: Five hundred
      and twenty items were randomly selected from two academic years for initial
      comparison; 270 from 2000 to 2001, and 250 from 2001 to 2002. The first set of
      items represented the style, content and format when courses and tests were
      departmentally/discipline based, assembled by course directors, and administered
      separately. The latter group represented similar characteristics when courses and
      tests were organ-system-based, committee-reviewed and administered in an
      integrated examination. Items were randomized, blinded for year of origin, and
      rated by three NBME staff members with extensive item review experience. A five
      point rating scale was used: one indicated a technically flawed item assessing
      recall of an isolated fact; five indicated a technically unflawed item assessing
      application of knowledge. To assess continued improvement, a follow-up set of 250
      items from the 2002 to 2003 academic year was submitted to the same three
      reviewers who were not informed of the purpose or origin of this set of test
      items. RESULTS: The mean rating for items from 2000 to 2001 was 2.51 +/- 1.27;
      analogous values for 2001-2002 were 3.16 +/- 1.33, (t = 5.83; p < 0.0001), and in
      2002-2003; 3.59 +/- 1.15 (t = 10.11; p<0.0001). CONCLUSION: Pre-established
      guidelines and an interdisciplinary review process resulted in improved item
      quality for in-house examinations.

PMID- 16583286
TI  - Alternative approaches to concept mapping and implications for medical education:
      commentary on reliability, validity and future research directions.

PMID- 16583287
TI  - Theory in practice: why "good medicine" and "scientific medicine" are not
      necessarily the same thing.
AB  - The term "scientific medicine", ubiquitous in medical literature although poorly
      defined, can be traced to a number of assumptions, three of which are examined in
      this paper: that medicine is a form of knowledge-driven practice, where the
      established body of proven medical knowledge determines what doctors do; if what
      doctors do is either inadequate or ineffective, the chief reason is the absolute
      or relative lack of adequate knowledge for providing care for patients;
      evaluating medical practice boils down to comparing it to a set of standards
      which should be univocally applied to concrete situations. This paper intends to
      provide at least a tentative assessment of how does this set of assumptions fare
      in the real world of clinical care. The methodology was based on direct
      observation of medical consultations and independent evaluation by referees of
      data from of medical records. The review of the data shows a far more contingent
      relationship between handbook prescribed procedures and actual medical practice,
      even though the referees evaluated the reported data mostly with favorable
      scores. Furthermore, a few problems were observed relating to the inadequacy of
      the so-called biomedical model in dealing with some of the more prevalent health
      problems. The authors conclude that, more than any "technical inadequacies", it
      would seem that this study has underlined the limitations of the biomedical model
      in responding to the tasks it attributes to itself, an issue that has to be
      addressed more effectively by medical education, be it in terms of undergraduate
      or graduate schooling.

PMID- 16583288
TI  - Viewing clinical research career development through the lens of social cognitive
      career theory.
AB  - Issues such as, over commitment, insufficient time, and lack of funding, threaten
      physicians' entry and sustainability in a research career pathway. Social
      cognitive career theory is presented as a conceptual framework to critically
      examine the limitations of the National Institutes of Health's (NIH) efforts to
      promote the career development of physician-scientists. Special attention is
      given to the unique challenges of promoting this career pathway for women and
      underrepresented minorities. The authors propose enhanced recommendations for the
      career development of physician-scientists and research questions for future
      studies and program development aimed at advancing the nation's efforts to
      promote clinical research.

PMID- 16583290
TI  - Stapled transanal rectal resection under laparoscopic surveillance for rectocele
      and concomitant enterocele.
AB  - PURPOSE: Stapled transanal rectal resection recently became a recommended
      surgical procedure for obstructed defecation syndrome. One problem when using a
      transanal stapling device for rectal surgery is the potential threat to
      structures located in front of the anterior rectal wall. We decided to perform a
      combined procedure of transanal rectal resection with a simultaneous laparoscopy
      for patients with obstructed defecation syndrome and an enterocele. METHODS:
      Between November 2002 and May 2005 a total of 41 patients were treated surgically
      for obstructed defecation syndrome. Four patients with concomitant enterocele
      underwent stapled transanal rectal resection under laparoscopic surveillance.
      Before surgery all patients underwent preoperative assessment, including clinical
      examination, colonoscopy, conventional video defecography, dynamic magnetic
      resonance imaging defecography, gynecology examinations, and psychologic
      evaluation. RESULTS: The mean operative time was 50 (+/-16.5) minutes for the
      conventional stapled transanal rectal resection and 67 (+/-14.1) minutes for
      combined laparoscopy and stapled transanal rectal resection (P < 0.01). Three
      major complications were observed: two had bleeding in the staple line (one from
      each group) and one had a late abscess in the staple line. CONCLUSIONS: The
      combination of the stapled transanal rectal resection procedure and laparoscopy
      provides the opportunity to perform transanal rectal resection without the threat
      of intra-abdominal lesions caused by enterocele.

PMID- 16583289
TI  - Impact of functional results on quality of life after rectal cancer surgery.
AB  - PURPOSE: Quality of life is an important outcome measure that has to be
      considered when deciding treatment strategy for rectal cancer. The aim of this
      study was to find out the impact of surgery-related adverse effects on quality of
      life. METHODS: The RAND-36 questionnaire and questionnaires assessing urinary,
      sexual, and bowel dysfunction were administered to 94 patients with no sign of
      recurrence a minimum of one year after curative surgery. Results were compared
      with age-matched and gender-matched general population. RESULTS: Eighty-two (87
      percent) patients answered the questionnaires. Major bowel dysfunction was as
      common after high anterior resection as after low anterior resection. Urinary
      complaints occurred as often after anterior resection as after abdominoperineal
      resection, but sexual dysfunction was more common after abdominoperineal
      resection. Overall, the patients reported better general health perception but
      poorer social functioning than population controls. In particular, elderly
      patients reported a significantly better quality of life in many dimensions than
      their population controls. There was no significant difference in quality of life
      between treatment groups. Major bowel dysfunction after anterior resection
      impaired social functioning compared with that of patients without such symptoms.
      Urinary dysfunction impaired social functioning and impotence impaired physical
      and social functioning. CONCLUSIONS: Quality of life after rectal cancer surgery
      is not worse than that of the general population. The major adverse impact of
      bowel and urogenital dysfunction is on social functioning. These adverse effects
      need to be discussed with the patient and preoperative function needs to be taken
      into account when choosing between treatment options. Permanent colostomy is not
      always the factor that disrupts a person's quality of life most.

PMID- 16583291
TI  - Location of early colorectal cancers at fold-top may reduce the risk of lymph
      node metastasis.
AB  - PURPOSE: This study was designed to look for significant correlations between
      location of early colorectal cancer, distance from muscularis mucosae to
      muscularis propria, and the frequency of lymph node metastasis. METHODS: A total
      of 166 early colorectal cancers, including 67 surgically resected lesions, were
      evaluated. The cancers were divided into two groups: metastatic and
      nonmetastatic. Cancer lesions were further subtyped at the fold-top or fold
      bottom. Macroscopic classifications and histology were performed. Absolute
      invasive depth and distance from muscularis mucosae to muscularis propria was
      measured. Multivariate analysis was used to assess relationships among the
      variables. RESULTS: The percentage of polypoid cancer lesions at fold-bottom was
      higher than at fold-top (74.5 vs. 51.8 percent), whereas flat-type cancer lesions
      at fold-bottom occurred less often than at fold-top (8.2 vs. 30.4 percent).
      Logistic regression showed that deep absolute invasive depth, lymphatic and
      vessel invasion, and cancer location (at fold-bottom) were the significant risk
      factors for early colorectal cancers leading to lymph-node metastasis. The
      distance from muscularis mucosae to muscularis propria with lymph-node metastasis
      (1,396.7 +/- 728.4 microm) was shorter than without lymph-node metastasis
      (3,533.9 +/- 2,507.8 microm; P < 0.01). Multivariate analysis showed that
      distance from muscularis mucosae to muscularis propria was a statistically
      significant factor for early colorectal cancers leading to lymph node metastasis
      (P = 0.0054). CONCLUSIONS: We conclude that early colorectal cancers at the fold
      top or with a long distance from muscularis mucosae to muscularis propria have
      less tendency to metastasize to lymph nodes. Clinically, these results provide
      evidence of a new indicator of endoscopic mucosal resection for early colorectal
      cancers at the fold-top.

PMID- 16583293
TI  - Endorectal ultrasonography in predicting rectal wall infiltration in patients
      with deep pelvic endometriosis: a modern tool for an ancient disease.
AB  - PURPOSE: This study evaluated the validity of endorectal ultrasonography in
      predicting rectal infiltration in patients with deep pelvic endometriosis.
      METHODS: Patients were recruited consecutively in the Department of Surgical
      Gynecology of Diaconesses Hospital from April 1996 to July 2003. Inclusion
      criteria were the suspicion of deep pelvic endometriosis on the basis of
      outpatient history and/or clinical symptoms with a mass palpable on bimanual
      examination that might infiltrate the rectal wall. There were no exclusion
      criteria. Endorectal ultrasonography was performed by the same investigator with
      a 7.5-MHz to 10-MHz rigid probe, producing a 360 degrees view of the rectal wall
      and adjacent areas. We used surgical and histopathologic findings as the "gold
      standard" to evaluate the validity of endorectal ultrasonography. RESULTS: This
      study was based on 37 patients (mean age, 35.8 (range, 26-46) years) who
      underwent surgery. The time between endorectal ultrasonography and surgery ranged
      from 4 to 529 (mean, 88.7) days. Eight patients had endometriosis nodules
      penetrating the rectal wall. Endorectal ultrasonography showed sensitivity,
      specificity, a positive predictive value, and a negative predictive value of
      87.5, 97, 87.5, and 97 percent, respectively, in the diagnosis of infiltration of
      the rectal wall by endometriosis. CONCLUSIONS: Endorectal ultrasonography is a
      reliable technique for visualizing rectal infiltration in patients with deep
      pelvic endometriosis. It should be more widely used by gynecologists because
      knowing about rectal infiltration before surgery is fundamental to defining the
      best possible surgical approach.

PMID- 16583292
TI  - Relationship between external anal sphincter atrophy at endoanal magnetic
      resonance imaging and clinical, functional, and anatomic characteristics in
      patients with fecal incontinence.
AB  - PURPOSE: External anal sphincter atrophy at endoanal magnetic resonance imaging
      has been associated with poor outcome of anal sphincter repair. We studied the
      relationship between external anal sphincter atrophy on endoanal magnetic
      resonance imaging and clinical, functional, and anatomic characteristics in
      patients with fecal incontinence. METHODS: In 200 patients (mean Vaizey score, 18
      (+/-2.9 standard deviation)) magnetic resonance images were evaluated for
      external anal sphincter atrophy (none, mild, or severe) by radiologists blinded
      to anorectal functional test results and details from medical history. Subgroups
      of patients with and without atrophy were compared for medical history, anal
      manometry, pudendal nerve latency testing, anal sensitivity testing, external
      anal sphincter thickness, and external anal sphincter defects. Whenever
      significant differences were detected, we tested for differences between patients
      with mild and severe atrophy. RESULTS: External anal sphincter atrophy was
      demonstrated in 123 patients (62 percent): graded as mild in 79 (40 percent), and
      severe in 44 patients (22 percent). Patients with atrophy were more often female
      (P < 0.001) and older (P = 0.003). They had a lower maximal squeeze (P = 0.01)
      and squeeze increment pressure (P < 0.001). Patients with severe atrophy had a
      lower maximal squeeze (P = 0.003) and squeeze increment pressure (P < 0.001) than
      patients with mild atrophy. These effects were not attenuated by potential
      confounding variables. Patients with atrophy could not be identified a priori by
      other characteristics. CONCLUSIONS: External anal sphincter atrophy at endoanal
      magnetic resonance imaging was depicted in 62 percent of patients, varying from
      mild to severe. Because increasing levels of atrophy were associated with
      impaired squeeze function, further studies are needed to evaluate whether grading
      atrophy is clinically valuable in selecting patients for anal sphincter repair.

PMID- 16583294
TI  - Gene expression, autonomic function and chronic hypoxia:lessons from the Andes.
AB  - Autonomic function is altered by altitude in sojourners and natives. We
      hypothesized that these physiologic responses are modulated by changes in gene
      expression. We compared gene product levels in 20 natives of Cerro de Pasco (CP),
      (4338 m), 10 of which had chronic mountain sickness (CMS) established by a CMS
      scoring system, with gene products in the same men after 1 h at sea level. We
      further compared the results with those obtained from 10 US men residing at 1500
      m. We measured gene products in white cells by reverse transcription polymerase
      chain reaction (RT-PCR). We focused on genes important in vascular autonomic
      physiology, and/or activated by hypoxia; hypoxia inducible factor 1-alpha (HIF 1
      alpha), 2 splicing variants of vascular endothelial growth factor (VEGF); VEGF
      121, VEGF-165, and phosphoglycerate kinase 1 (PGK 1). Normal CP natives showed
      high expression of all genes in CP, compared to US controls. Within 1 h of
      arrival at sea level, they had comparable levels to US residents. In CMS, the
      gene products were higher in CP. Although gene products decreased in Lima in this
      group, they never reached US values. VEGF 121 and 165 were correlated (P<0.001).
      VEGF 165 was higher in CMS in CP (P=0.006), and was positively correlated with
      CMS-score (R=0.86, P<0.001), and negatively correlated with arterial saturation
      (R=-0.79, P<0.001). Our findings underscore the changes in gene expression levels
      in intact humans in response to environmental stress. These changes may support
      the physiologic alterations induced by the ambient hypoxia at altitude and impact
      organism survival. They also suggest therapeutic strategies for autonomic and
      neurodegenerative diseases at sea level.

PMID- 16583296
TI  - Inference methods for correlated left truncated lifetimes: parent and offspring
      relations in an adoption study.
AB  - The associations in mortality of adult adoptees and their biological or adoptive
      parents have been studied in order to separate genetic and environmental
      influences. The 1003 Danish adoptees born 1924-26 have previously been analysed
      in a Cox regression model, using dichotomised versions of the parents' lifetimes
      as covariates. This model will be referred to as the conditional Cox model, as it
      analyses lifetimes of adoptees conditional on parental lifetimes. Shared frailty
      models may be more satisfactory by using the entire observed lifetime of the
      parents. In a simulation study, sample size, distribution of lifetimes,
      truncation- and censoring patterns were chosen to illustrate aspects of the
      adoption dataset, and were generated from the conditional Cox model or a shared
      frailty model with gamma distributed frailties. First, efficiency was compared in
      the conditional Cox model and a shared frailty model, based on the conditional
      approach. For data with type 1 censoring the models showed no differences,
      whereas in data with random or no censoring, the models had different power in
      favour of the one from which data were generated. Secondly, estimation in the
      shared frailty model by a conditional approach or a two-stage copula approach was
      compared. Both approaches worked well, with no sign of dependence upon the
      truncation pattern, but some sign of bias depending on the censoring. For frailty
      parameters close to zero, we found bias when the estimation procedure used did
      not allow negative estimates. Based on this evaluation, we prefer to use frailty
      models allowing for negative frailty parameter estimates. The conclusions from
      earlier analyses of the adoption study were confirmed, though without greater
      precision than using the conditional Cox model. Analyses of associations between
      parental lifetimes are also presented.

PMID- 16583297
TI  - Inference for the dependent competing risks model with masked causes of failure.
AB  - The competing risks model is useful in settings in which individuals/units may
      die/fail for different reasons. The cause specific hazard rates are taken to be
      piecewise constant functions. A complication arises when some of the failures are
      masked within a group of possible causes. Traditionally, statistical inference is
      performed under the assumption that the failure causes act independently on each
      item. In this paper we propose an EM-based approach which allows for dependent
      competing risks and produces estimators for the sub-distribution functions. We
      also discuss identifiability of parameters if none of the masked items have their
      cause of failure clarified in a second stage analysis (e.g. autopsy). The
      procedures proposed are illustrated with two datasets.

PMID- 16583298
TI  - A method for analyzing disease-specific mortality with missing cause of death
      information.
AB  - In this paper, we examine a method for analyzing competing risks data where the
      failure type of interest is missing or incomplete, but where there is an
      intermediate event, and only patients who experience the intermediate event can
      die of the cause of interest. In some applications, a method called "log-rank
      subtraction" has been applied to these problems. There has been no systematic
      study of this methodology, though. We investigate the statistical properties of
      the method and further propose a modified method by including a weight function
      in the construction of the test statistic to correct for potential biases. A
      class of tests is then proposed for comparing the disease-specific mortality in
      the two groups. The tests are based on comparing the difference of weighted log
      rank scores for the failure type of interest. We derive the asymptotic properties
      for the modified test procedure. Simulation studies indicate that the tests are
      unbiased and have reasonable power. The results are also illustrated with data
      from a breast cancer study.

PMID- 16583299
TI  - Nonparametric estimation of sojourn time distributions for truncated serial event
      data--a weight-adjusted approach.
AB  - In follow-up studies, survival data often include subjects who have had a certain
      event at recruitment and may potentially experience a series of subsequent events
      during the follow-up period. This kind of survival data collected under a cross
      sectional sampling criterion is called truncated serial event data. The outcome
      variables of interest in this paper are serial sojourn times between successive
      events. To analyze the sojourn times in truncated serial event data, we need to
      confront two potential sampling biases arising simultaneously from a sampling
      criterion and induced informative censoring. In this study, nonparametric
      estimation of the joint probability function of serial sojourn times is developed
      by using inverse probabilities of the truncation and censoring times as weight
      functions to accommodate these two sampling biases under various situations of
      truncation and censoring. Relevant statistical properties of the proposed
      estimators are also discussed. Simulation studies and two real data are presented
      to illustrate the proposed methods.

PMID- 16583300
TI  - Implications of model misspecification in robust tests for recurrent events.
AB  - Chronic disease processes often feature transient recurrent adverse clinical
      events. Treatment comparisons in clinical trials of such disorders must be based
      on valid and efficient methods of analysis. We discuss robust strategies for
      testing treatment effects with recurrent events using methods based on marginal
      rate functions, partially conditional rate functions, and methods based on
      marginal failure time models. While all three approaches lead to valid tests of
      the null hypothesis when robust variance estimates are used, they differ in
      power. Moreover, some approaches lead to estimators of treatment effect which are
      more easily interpreted than others. To investigate this, we derive the limiting
      value of estimators of treatment effect from marginal failure time models and
      illustrate their dependence on features of the underlying point process, as well
      as the censoring mechanism. Through simulation, we show that methods based on
      marginal failure time distributions are shown to be sensitive to treatment
      effects delaying the occurrence of the very first recurrences. Methods based on
      marginal or partially conditional rate functions perform well in situations where
      treatment effects persist or in settings where the aim is to summarizee long-term
      data on efficacy.

PMID- 16583301
TI  - A corrected pseudo-score approach for additive hazards model with longitudinal
      covariates measured with error.
AB  - In medical studies, it is often of interest to characterize the relationship
      between a time-to-event and covariates, not only time-independent but also time
      dependent. Time-dependent covariates are generally measured intermittently and
      with error. Recent interests focus on the proportional hazards framework, with
      longitudinal data jointly modeled through a mixed effects model. However,
      approaches under this framework depend on the normality assumption of the error,
      and might encounter intractable numerical difficulties in practice. This
      motivates us to consider an alternative framework, that is, the additive hazards
      model, about which little research has been done when time-dependent covariates
      are measured with error. We propose a simple corrected pseudo-score approach for
      the regression parameters with no assumptions on the distribution of the random
      effects and the error beyond those for the variance structure of the latter. The
      estimator has an explicit form and is shown to be consistent and asymptotically
      normal. We illustrate the method via simulations and by application to data from
      an HIV clinical trial.

PMID- 16583302
TI  - Sampling scale effects in random fields and implications for environmental
      monitoring.
AB  - The concept of a sampling scale triplet of spacing, extent and support is used to
      define the spatial dimensions of a monitoring network or a field study. The
      spacing is the average distance between samples, the extent is the size of the
      domain sampled and the support is the averaging area of one sample. The aim of
      this paper is to examine what is the bias and the random error (uncertainty)
      introduced by the sampling scale triplet into estimates of the mean, the spatial
      variance and the integral scale of a variable in a landscape. The integral scale
      is a measure of the average distance over which a variable is correlated in
      space. A large number of two dimensional random fields are generated from which
      hypothetical samples, conforming to a certain sampling scale triplet, are drawn
      which in turn are used to estimate the sample mean, spatial variance and integral
      scale. The results indicate that the biases can be up to two orders of magnitude.
      The bias of the integral scale is positively related to the magnitude of any of
      the components of the scale triplet while the bias of the spatial variance is
      different for different components of the scale triplet. All sampling scale
      effects are relative to the underlying correlation length of the variable of
      interest which is closely related to the integral scale. The integral scale can
      hence be used for sampling design and data interpretation. Suggestions are given
      on how to adjust a monitoring network to the scales of the variables of interest
      and how to interpret sampling scale effects in environmental data.

PMID- 16583303
TI  - The effects of subchronic methidathion toxicity on rat liver: role of antioxidant
      vitamins C and E.
AB  - Methidathion (MD) phosphorodithioic acid S-[(5-methoxy-2-oxo-1,3,4-thiadiazol
      3(2H)-yl)methyl] O,O-dimethyl ester is the organophosphate insecticide (OPI) most
      commonly used worldwide in the pest control of crops. Subchronic MD exposure was
      evaluated for its effects on lipid peroxidation, the serum activities of
      cholinesterase (ChE), and enzymes concerning liver damage, and the protective
      effects of combination of vitamins E and C in albino rats. Additionally, the
      histopathological changes in liver tissue were examined. Experimental groups were
      as follows: control group; a group treated with 5 mg/kg body weight MD (MD
      group); and a group treated with 5 mg/kg body wight MD plus vitamin E plus
      vitamin C (MD+AO group). The MD and MD+AO groups were treated orally with MD on
      five days a week for 4 weeks. The serum activities of cholinesterase (ChE),
      alanine transferase (ALT), aspartate amiotransferase (AST), lactate dehydrogenase
      (LDH), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and the
      concentration of malondialdehyde (MDA) and liver histopathology were studied. In
      serum samples, MD significantly increased MDA concentration and ALP, AST, GGT,
      LDH activities but decreased the ALT and ChE activities. In the MD+AO group, MDA
      level and ALP, AST, LDH activities were significantly decreased and ChE activity
      was increased compared to the MD group. Histopathological changes found in liver
      tissue of rats treated with MD included were infiltration with mononuclear cells
      in all portal areas, sinusoidal dilatation, and focal microvesicular steatosis
      and hydropic degenerations in parenchymal tissue. The severity of these lesions
      was reduced by administration of vitamins. From these results, it can be
      concluded that subchronic MD causes liver damage, and lipid peroxidation may be a
      molecular mechanism involved in MD-induced toxicity. Furthermore, the combination
      of vitamins E and C can reduce the toxic effects of MD on liver tissue of rats.

PMID- 16583304
TI  - Factors affecting the pharmacokinetic profile of MS-275, a novel histone
      deacetylase inhibitor, in patients with cancer.
AB  - AIMS: To evaluate elimination pathways of the histone deacetylase inhibitor MS
      275 in vitro and screen for relationships between demographic factors that may
      affect its pharmacokinetics in vivo. PATIENTS AND METHODS: Substrate specificity
      of MS-275 for the liver-specific organic anion transporting polypeptides (OATPs)
      was assessed using Xenopus laevis oocytes, and in vitro metabolism was evaluated
      using human liver microsomes. In vivo pharmacokinetic data were obtained from 64
      adult patients (36 male/28 female; median age, 57 years) receiving MS-275 orally
      (dose range, 2 to 12 mg/m2). RESULTS: Accumulation of [G-3H]MS-275 by oocytes
      expressing OATP1B1 or OATP1B3 was not significantly different from water-injected
      controls (p = 0.82). Furthermore, no metabolites could be detected after
      incubation of MS-275 in human liver microsomes, suggesting that hepatic
      metabolism is a minor pathway of elimination. The mean (+/- SD) apparent oral
      clearance of MS-275 was 38.5 +/- 18.7 L/h, with a coefficient of variation (%CV)
      of 48.7%. When clearance was adjusted for body-surface area (BSA), the inter
      individual variability was similar (%CV = 50.1%). In addition, in a linear
      regression analysis, except for adjusted ideal body weight (p = 0.02, |r| =
      0.29), none of the studied measures (BSA, lean-body mass, ideal body weight, body
      mass index, height, weight, age, and sex) was a significant covariate (p > 0.13;
      |r| < 0.11) for oral clearance. CONCLUSIONS: The current analysis has eliminated
      a number of candidate covariates from further consideration as important
      determinants of MS-275 absorption and disposition. Furthermore, MS-275 can be
      added to the list of cancer drugs where BSA-based dosing is not more accurate
      than fixed dosing.

PMID- 16583305
TI  - Increased transglutaminase activity was associated with IL-6 release in cultured
      human gingival fibroblasts exposed to dental cast alloys.
AB  - Molecular mechanisms underlying gingival and periodontal inflammation caused by
      dental alloys are still poorly understood. Recently, it has been demonstrated
      that tissue transglutaminase can be involved in inflammatory cell response. The
      aim of this study was to evaluate effects of exposure to orthodontic materials on
      transglutaminase in cultured human gingival fibroblasts. The incubation with Ni
      Ti heat-activated (T3) or Ni-Ti super-elastic (T4), and with Ni-Cr-Co (T2) alloys
      produced respectively 2.5-fold and 8-fold increases in IL-6 release compared with
      control cultures. Transglutaminase activity was significantly increased in cells
      exposed to T3 and T4 alloys (about 170% of control; p < 0.05), where it was
      mainly localized close to inner part of cell membrane. The exposure to T3 and T4
      specimens significantly up-regulated also tTG expression compared with control
      cultures. These data first show an association between IL-6 release and tissue
      transglutaminase increases, suggesting that TGase-mediated reactions may play a
      major role in periodontal inflammation.

PMID- 16583306
TI  - Phthalocyanine-dyed fibers adsorb allergenic proteins.
AB  - Phthalocyanine (Pc)-dyed fiber is reported to reduce atopic symptoms in some
      patients when they use underwear made of the fiber. We investigated the
      adsorption of allergens on Pc-fiber. Pc-fiber trapped house dust/pollen/food
      allergens with varied molecular weight and pI. The adsorbed allergens were
      released in the presence of mild detergent. Pc-fiber did not change the molecular
      weight or disulfide bonding of the allergens. These observations imply that Pc
      fiber is applicable as an "allergen trap" for a wide variety of products.

PMID- 16583307
TI  - The effect of taurine depletion on the contractile properties and fatigue in fast
      twitch skeletal muscle of the mouse.
AB  - Taurine increases force production in skeletal muscle, and taurine levels may
      fall during exercise. The contractile properties and fatigability of extensor
      digitorum longus (EDL) muscles depleted of taurine by guanodinoethane sulfonate
      (GES) treatment were investigated. GES treatment decreased muscle taurine levels
      to <40% of controls. Peak twitch force levels were 23% of controls in GES treated
      EDL muscles (p < 0.05), but maximal specific force was unaffected. The force
      frequency relationship was examined and significantly less force was produced by
      the GES treated muscles compared to controls at stimulation frequencies from 50
      to 100 Hz (p < 0.05). GES treated EDL muscles exhibited significantly slower
      rates of fatigue than controls (p < 0.05). In skinned fibres, 20 mM GES had a
      small but significant effect on force production, indicating that GES may have
      some minor taurine-like effects. In this study, a fall in taurine levels
      decreased force output, and increased the endurance of EDL skeletal muscles.

PMID- 16583308
TI  - Site specificity of glycation and carboxymethylation of bovine serum albumin by
      fructose.
AB  - We report an investigation of the site specificity, extent and nature of
      modification of bovine serum albumin (BSA) incubated with fructose or glucose at
      physiological temperature and pH. Sites of early glycation (Heyns rearrangement
      products (HRP) from fructose; fructoselysine (FL) from glucose) as well as
      advanced glycation (N(epsilon)-(carboxymethyl)lysine; CML) were analyzed by
      liquid chromatography-mass spectrometry. The major site of modification by
      fructose, like glucose, is Lysine-524 and this results in, respectively, 31 and
      76% loss of the corresponding unmodified tryptic peptide, Gln525-Lys533. In
      addition, total lysine, HRP, FL, CML and N(epsilon)-(carboxyethyl)lysine in the
      incubations, was quantified. Almost all of the loss of lysine in the fructose
      modified BSA was attributed to the formation of CML, with the yield of CML being
      up to 17-fold higher than glucose-modified BSA. A mechanism for the formation of
      CML from the HRP is proposed.

PMID- 16583309
TI  - High concentrations of D-amino acids in human gastric juice.
AB  - The concentrations of free D- and L-amino acids were determined in the gastric
      juice from four groups: patients suffering from early gastric carcinoma with or
      without Helicobacter pylori infection, and patients without carcinoma but with
      peptic ulcers, duodenal ulcers or chronic gastritis with or without H. pylori
      infection. H. pylori is a bacterium associated with gastric inflammation and
      peptic ulcers and is a risk factor for stomach cancer. The highest D-amino acid
      ratios (free D-amino acid concentration to the total corresponding free D- and L
      amino acid concentration) were 29%, 26%, 18%, 4% and 1% for proline, alanine,
      serine, aspartate and glutamate, respectively. The gastric juice levels of L
      alanine, L-serine, L-proline, L-glutamate and D-alanine in the samples obtained
      from subjects bearing early gastric carcinoma and H. pylori were significantly
      higher than in the samples from the other three groups. Except for D-alanine,
      there was no correlation between the D-amino acid concentrations and presence of
      carcinoma or H. pylori.

PMID- 16583310
TI  - The relationship between albumin, other plasma proteins and variables, and age in
      the acute phase response after liver resection in man.
AB  - A large series of plasma albumin (ALB, g/dl) and simultaneous blood and clinical
      measurements were prospectively performed on 92 liver resection patients, and
      processed to assess the correlations between ALB, other plasma proteins,
      additional variables and clinical events. The measurements were performed
      preoperatively and at postoperative day 1, 3 and 7 in all patients, and
      subsequently only in those who developed complications or died. In patients who
      recovered normally ALB was 4.3 +/- 0.4 g/dl (mean +/- SD) preoperatively, 3.7 +/-
      0.7 at day 1 and 3, and 3.9 +/- 0.4 at day 7. In patients with complications its
      decrease was more prolonged. In non-survivors it was 3.4 +/- 0.4 preoperatively,
      3.0 +/- 0.4 at day 1, and then decreased further. Regression analysis showed
      direct correlations between ALB and pseudo-cholinesterase (CHE, U/l, nv 5300
      13000), cholesterol (CHOL, mg/dl), iron binding capacity (IBC, mg/dl),
      prothrombin activity (PA, % of standard reference) and fibrinogen, an inverse
      correlation with blood urea nitrogen (BUN, mg/dl) for any given creatinine level
      (CREAT, mg/dl), and weaker direct correlations with hematocrit, other variables
      and dose of exogenous albumin. An inverse relationship found between ALB and age
      (AGE, years) became postoperatively (POSTOP) also a function of outcome, showing
      larger age-related decreases in ALB associated with complications (COMPL: sepsis,
      liver insufficiency) or death (DEATH). Main overall correlations: CHE =
      287.4(2.014)(ALB), r = 0.73; CHOL = 16.5(1.610)(ALB) (1.001)(ALKPH), r = 0.71;
      IBC = 68.6(1.391)(ALB), r = 0.64; PA = 13.8 + 16.0(ALB), r = 0.51; BUN = 21.3 +
      20.2(CREAT) - 6.2(ALB), r = 0.91; ALB = 5.0-0.013(AGE) - {0.5 + 0.003(AGE)( COMPL
      ) + 0.012(AGE)( DEATH )}( POSTOP ), r = 0.74 [p < 0.001 for each regression and
      each coefficient; ALKPH = alkaline phosphatase, U/l, nv 98-279, independent
      determinant of CHOL; discontinuous variables in italics label the change in
      regression slope or intercept associated with the corresponding condition]. These
      results suggest that altered albumin synthesis (or altered synthesis unable to
      compensate for albumin loss, catabolism or redistribution) is an important
      determinant of hypoalbuminemia after hepatectomy. The correlations with age and
      postoperative outcome support the concept that hypoalbuminemia is a marker of
      pathophysiologic frailty associated with increasing age, and amplified by the
      challenges of postoperative illness.

PMID- 16583311
TI  - Effects of glucocorticoids on polyamine metabolism in liver and spleen of guinea
      pig during sensitization.
AB  - Glucocorticoids are potent anti-inflammatory and immunosuppressive agents. As
      endogenous inhibitors of cytokine synthesis, glucocorticoids suppress immune
      activation and uncontrolled overproduction of cytokines, preventing tissue
      injury. Also, polyamine spermine is endogenous inhibitor of cytokine production
      (inhibiting IL-1, IL-6 and TNF synthesis). The idea of our work was to examine
      dexamethasone effects on the metabolism of polyamines, spermine, spermidine and
      putrescine and polyamine oxidase activity in liver and spleen during
      sensitization of guinea pigs. Sensitization was done by application of bovine
      serum albumin with addition of complete Freund's adjuvant. Our results indicate
      that polyamine amounts and polyamine oxidase activity increase during
      immunogenesis in liver and spleen. Dexamethasone application to sensitized and
      unsensitized guinea pigs causes depletion of polyamines in liver and spleen.
      Dexamethasone decreases polyamine oxidase activity in liver and spleen of
      sensitized guinea pigs, increasing at the same time PAO activity in tissues of
      unsensitized animals.

PMID- 16583312
TI  - Eye lens proteomics.
AB  - The eye lens is a fascinating organ as it is in essence living transparent
      matter. Lenticular transparency is achieved through the peculiarities of lens
      morphology, a semi-apoptotic process where cells elongate and loose their
      organelles and the precise molecular arrangement of the bulk of soluble
      lenticular proteins, the crystallins. The 16 crystallins ubiquitous in mammals
      and their modifications have been extensively characterized by 2-DE, liquid
      chromatography, mass spectrometry and other protein analysis techniques. The
      various solubility dependant fractions as well as subproteomes of lenticular
      morphological sections have also been explored in detail. Extensive post
      translational modification of the crystallins is encountered throughout the lens
      as a result of ageing and disease resulting in a vast number of protein species.
      Proteomics methodology is therefore ideal to further comprehensive understanding
      of this organ and the factors involved in cataractogenesis.

PMID- 16583313
TI  - Aberrant expression of cytoskeleton proteins in hippocampus from patients with
      mesial temporal lobe epilepsy.
AB  - Mesial temporal lobe epilepsy (MTLE), the most common form of epilepsy, is
      characterised by cytoarchitectural abnormalities including neuronal cell loss and
      reactive gliosis in hippocampus. Determination of aberrant cytoskeleton protein
      expression by proteomics techniques may help to understand pathomechanism that is
      still elusive. We searched for differential expression of hippocampal proteins by
      an analytical method based on two-dimensional gel electrophoresis (2-DE) coupled
      with mass spectrometry unambiguously identifying 77 proteins analysed in eight
      control and eight MTLE hippocampi. Proteins were quantified and we observed 18
      proteins that were altered in MTLE. Cytoskeleton proteins tubulin alpha-1 chain,
      beta-tubulin, profilin II, neuronal tropomodulin were significantly reduced and
      one actin spot was missing, whereas ezrin and vinculin were significantly
      increased in MTLE. Proteins of several classes as e.g. antioxidant proteins
      (peroxiredoxins 3 and 6), chaperons (T-complex protein 1-alpha, stress-induced
      phosphoprotein 1), signaling protein MAP kinase kinase 1, synaptosomal proteins
      (synaptotagmin I, alpha-synuclein), NAD-dependent deacetylase sirtuin-2 and 26S
      protease regulatory subunit 7 protein, neuronal-specific septin 3 were altered in
      MTLE. Taken together, the findings may represent or lead to cytoskeletal
      impairment; aberrant antioxidant proteins, chaperons, MAP kinase kinase 1 and NAD
      dependent deacetylase sirtuin-2 may have been involved in pathogenetic mechanisms
      and altered synaptosomal protein expression possibly reflects synaptic impairment
      in MTLE.

PMID- 16583314
TI  - Adrenomedullin: molecular mechanisms and its role in cardiac disease.
AB  - Adrenomedullin (AM) is a potent, long-lasting vasoactive peptide originally
      isolated from human pheochromocytoma. Since its discovery, serum and tissue AM
      expression have been shown to be increased in experimental models and in patients
      with cardiac hypertrophy, myocardial infarction and end-stage heart failure with
      several beneficial effects. Considerable evidence exists for a wide range of
      autocrine, paracrine and endocrine mechanisms for AM which include vasodilatory,
      anti-apoptotic, angiogenic, anti-fibrotic, natriuretic, diuretic and positive
      inotropic. Thus, through regulation of body fluid or direct cardiac mechanisms,
      AM has additive and beneficial effects in the context of heart disease. Notable
      molecular mechanisms of AM include cyclic adenosine monophosphate, guanosine
      3',5'-monophosphate, PI3K/Akt and MAPK-ERK-mediated cascades. Given the
      endogenous and multifunctional nature of AM, we consider this molecule to have
      great potential in the treatment of cardiovascular diseases. In agreement, early
      experimental and preliminary clinical studies suggest that AM is a new and
      promising therapy for cardiovascular diseases.

PMID- 16583315
TI  - Laccase-induced derivatization of unprotected amino acid L-tryptophan by coupling
      with p-hydroquinone 2,5-dihydroxy-N-(2-hydroxyethyl)-benzamide.
AB  - We have studied the enzymatic derivatization of amino acids by use of the
      polyphenol oxidase laccase. Derivatization of L-tryptophan was achieved by
      enzymatic crosslinking with the laccase substrate 2,5-dihydroxy-N-(2
      hydroxyethyl)-benzamide. The main product (yield up to 70%) was identified as the
      quinoid compound 2-[2-(2-hydroxy-ethylcarbamoyl)-3,6-dioxo-cyclohexa-1,4
      dienylamino]-3-(1H-indol-3-yl)- propionic acid and demonstrates that laccase
      catalyzed C-N-coupling occurred on the amino group of the aliphatic side chain.
      These enzyme based reactions provide a simple and fast method for the
      derivatization of unprotected amino acids.

PMID- 16583316
TI  - Brain G protein-dependent signaling pathways in Down syndrome and Alzheimer's
      disease.
AB  - Premature aging and neuropathological features of Alzheimer's disease (AD) are
      commonly observed in Down syndrome (DS). Based on previous findings in a DS mouse
      model, the function of signaling pathways associated with adenylyl cyclase (AC)
      and phospholipase C (PLC) was assessed in cerebral cortex and cerebellum of age
      matched adults with DS, AD, and controls. Basal production of cAMP was reduced in
      DS but not in AD cortex, and in both, DS and AD cerebellum. Responses to
      GTPgammaS, noradrenaline, SKF 38393 and forskolin were more depressed in DS than
      in AD cortex and cerebellum. Although no differences in PLC activity among
      control, DS and AD cortex were observed under basal and GTPgammaS- or Ca
      stimulated conditions, the response of DS cortex to serotonergic and cholinergic
      stimulation was depressed, and that of AD was only impaired at cholinergic
      stimulation. No differences were documented in cerebellum. Our results
      demonstrate that PLC and AC were severely disturbed in the aged DS and AD brains,
      but the alterations in DS were more severe, and differed to some extent from
      those observed in AD.

PMID- 16583317
TI  - GABA-mediated effects of some taurine derivatives injected i.c.v. on rabbit
      rectal temperature and gross motor behavior.
AB  - Some synthetic taurine analogues, namely ethanolamine-O-sulphate (EOS), N,N
      dimethyltaurine (DMT), N,N,N-trimethyltaurine (TMT) and 2-aminoethylphosphonic
      acid (AEP) were shown to interact with rabbit brain GABA(A)- or GABA(B)
      receptors, while (+/-)piperidine-3-sulfonic acid (PSA) inhibited the activity of
      rabbit brain 4-aminobutyrate transaminase. This suggests that they behave like
      direct/indirect GABA agonists or GABA antagonists and affect thermoregulation and
      gross motor behaviour (GMB) which are under GABA control. In the present study
      micromole (1.2-48) amounts of these compounds were i.c.v. injected in conscious,
      restrained rabbits while monitoring rectal temperature (RT), ear skin temperature
      (EST) and GMB. AEP, EOS, DMT and TMT induced a dose-related hyperthermia, ear
      vasoconstriction and excitation of GMB, while PSA induced a dose-related
      hypothermia, ear vasodilation and inhibition of GMB. EOS antagonized in a dose
      related fashion hypothermia induced by 60 nmol THIP, a GABA(A) agonist, while
      AEP, DMT and TMT counteracted that induced by 8 nmol R(-)Baclofen, a GABA(B)
      agonist. In conclusion, EOS and AEP, DMT, TMT seem to act as GABA(A) and GABA(B)
      antagonists, respectively, while PSA behaves like an indirect GABA agonist, all
      affecting the central mechanisms which drive rabbit thermoregulation.

PMID- 16583318
TI  - Isotopic effects in the electronic spectra of tryptophan.
AB  - No influence of isotopic substitution in deuterium-substituted tryptophan on the
      florescence excitation spectrum has previously been found out. Here, the isotopic
      effects of electronic excitation of deuterium-substituted tryptophan were
      experimentally and theoretically analyzed for first time. It was shown a short
      wave shift of the UV-absorption maximum at 220 nm corresponding to the 360
      cal/mol and short-wave shift for fluorescence spectrum corresponding to the 210
      cal/mol. To account for this effect, the quantum chemical calculations of the
      geometric and electron structure, frequencies of normal vibrations and transition
      energies have been performed. The isotopic effects originate from the zero-point
      energies of ground and excited states. It was found that isotopic shifts depend
      on the position of isotope in the molecule and kind of transition. So, it can be
      utilized in the analysis of proteins structure and complexation.

PMID- 16583319
TI  - Extracellular matrix containing mutated fibrillin-1 (Fbn1) down regulates Col1a1,
      Col1a2, Col3a1, Col5a1, and Col5a2 mRNA levels in Tsk/+ and Tsk/Tsk embryonic
      fibroblasts.
AB  - It is known that the extracellular matrix (ECM) is able to signal to cells and
      thereby direct or modulate the transcription of certain mRNAs. This signaling
      plays an important role in tumor invasion and metastasis, wound healing,
      remodeling of the ECM and cell differentiation. There are several mechanisms
      whereby the ECM signals cells to change their metabolism: (1) receptor molecules
      binding to specific domains in the ECM, (2) direct phagocytosis of the ECM
      molecules or domains into the cell, (3) structural changes of the ECM domains. We
      report the effect of an ECM containing either mutant or normal Fbn1 on the
      transcription levels of several collagen mRNAs. Tsk/Tsk, Tsk/+ and +/+ mouse
      embryonic fibroblast cell lines were used. Tsk/Tsk cells produce only mutated
      fibrillin-1 which arises from mRNA containing an in-frame duplication of exons 17
      40. To test the effect of the ECM containing mutant Fbn1, cells of the Tsk/Tsk,
      Tsk/+ and the wild-type (+/+) genotype were each grown on an ECM produced by
      either Tsk/Tsk, Tsk/+ cells or by wild-type cells (+/+). The embryonic cells were
      genotyped by Northern analyses for Fbn1 and grown to confluence. The cultures
      were then harvested and the cells removed, leaving the matrix in the flasks.
      Matrices produced from Tsk/Tsk, Tsk/+ and from +/+ cells were reseeded with
      Tsk/Tsk cells, Tsk/+ cells or +/+ cells. The cells were plated at a confluent
      concentration and incubated on the matrices for 48 h, after which total RNA was
      harvested and cDNA generated. Real-time PCR using cDNA or Northern analyses using
      RNA were performed for Fbn1 and Types I, III and V collagens. The PCR and
      Northern results were normalized using beta-actin and GAPDH, respectively. The
      Northern analyses showed that the steady state levels of mRNA for Col1a1 were
      depressed in both Tsk/Tsk and +/+ cells when grown on the matrix produced by
      Tsk/Tsk cells. Real-time PCR was then performed with primers specific for Col1a2,
      Col3a1, Col5a1 and Col5a2. The results showed that cells with the Tsk/Tsk, Tsk/+,
      and +/+ genotype all had lower steady-state levels of the above 4 collagen mRNAs
      when grown on the matrix produced by homozygous Tsk/Tsk cells or the matrix
      produced by heterozygous Tsk/+ cells compared with those grown on a matrix
      produced by +/+ cells. We hypothesize that the mutated Fbn1 molecules with many
      additional EGF-calcium binding regions and TGF-beta binding domains may (1)
      change the homeostasis of the ECM by binding additional growth factors and/or (2)
      present a radically different ECM 3-dimensional architecture. Either or both of
      these changes could signal the cell to produce less collagen.

PMID- 16583320
TI  - Synthesis and characterization of aspartic acid complexes of antimony and bismuth
      triiodide.
AB  - New bioinorganic complexes of the aspartic acid with the antimony or bismuth
      triiodide were synthesized by a direct solid-solid reaction at room temperature.
      The formula of the complex is MI(3)[OOCCH(2)CH(NH(2))CO](2.5) x 2.5H(2)O (M = Sb,
      Bi). The complex may be a dimer with bridge structure. The crystal structure of
      the complexes belongs to a triclinic system. The lattice parameters are a =
      0.9883 nm, b = 1.4284 nm, c = 2.0114 nm, alpha = 94.46 degrees , beta = 99.76
      degrees and gamma = 100.1 degrees for the complex of antimony and a = 0.9756 nm,
      b = 1.4560 nm, c = 1.9875 nm, alpha = 94.18 degrees , beta = 97.25 degrees and
      gamma = 101.16 degrees for the complex of bismuth. The infrared spectra and
      thermal analyses can demonstrate the complex formation between the aspartic acid
      and the antimony or bismuth ion.

PMID- 16583323
TI  - Persistent high NTpro-BNP concentration as a negative prognostic factor in
      patients with decompensated heart failure.
AB  - INTRODUCTION: Monitoring of natriuretic peptide concentration may be useful for
      the identification of high-risk patients presenting with decompensated chronic
      heart failure (CHF). AIM: Assessment of the predicting value of a significant
      decrease (by > or =20% vs. baseline) of N-terminal proBNP (NTpro-BNP, ROCHE)
      concentration during hospitalisation in patients with decompensated CHF. METHODS:
      This study involved 54 patients admitted to our centre because of CHF
      decompensation. Concentration of NTpro-BNP was measured on admission and at
      discharge from hospital. Primary end-points of this study were overall mortality
      and mortality with a number of cardiovascular-related readmissions. RESULTS: Mean
      NTpro-BNP concentration on admission was 7435+/-10040 pg/ml and at the time of
      discharge from hospital -- 4816+/-7822 pg/ml. In 31 (57%) patients a significant
      decrease (> or =20% vs baseline value) in NTpro-BNP level (mean: -58%+/-21%) was
      noted, while in the remainder (23 patients; 43%) neither an increase nor a
      decrease in NTpro-BNP levels was observed (mean: +72%+/-132%) despite optimal
      treatment and stabilisation of the clinical status. The mean follow-up duration
      was 358+/-240 days. Cox analysis showed that the absence of significant NTpro-BNP
      level decrease was associated with an increased risk of death -- RR: 3.69 (95%
      CI: 1.10-12.37; p=0.035) and was the single independent risk factor for
      readmission due to cardiovascular-related reasons and/or death -- RR: 2.29 (95%
      CI: 1.20-4.35; p=0.01). In the group of 23 patients with an increase or decrease
      in NTpro-BNP concentration of more than or equal to 20%, the survival rate was
      65% vs. 87% in the remainder (p=0.02). CONCLUSIONS: The lack of a significant (>
      or =20%) decrease of NTpro-BNP level during hospitalisation correlates with a
      higher mortality and rate of readmissions. NTpro-BNP level monitoring may be of
      clinical importance for risk stratification in patients hospitalised for
      decompensated CHF.

PMID- 16583321
TI  - Angiographic and clinical outcome after percutaneous coronary interventions
      following combined fibrinolytic therapy in acute myocardial infarction.
AB  - INTRODUCTION: Combined therapy with fibrinolytic agent and platelet GPIIb/IIIa
      inhibitor not followed by an interventional procedure does not improve prognosis
      in patients presenting with acute ST-segment elevation myocardial infarction
      (STEMI) when compared to fibrinolysis alone. On the other hand, in the past
      percutaneous coronary interventions (PCI) performed after fibrinolysis were
      associated with low angiographic efficacy, a high risk of bleeding and a high
      rate of early cardiovascular events. AIM: Evaluation of angiographic and clinical
      outcomes in patients with STEMI treated with PCI following combined fibrinolytic
      therapy. METHODS AND RESULTS: Complete angiographic and clinical data of 187
      patients who underwent PCI immediately after combined fibrinolytic therapy were
      obtained from a survey of 669 consecutive patients with STEMI <12 hours, at age
      <75 years, without cardiogenic shock, who were transferred from regional
      hospitals to the catheterisation laboratory within 90 minutes and after the
      initiation of combined fibrinolytic therapy (alteplase 15 mg iv as a bolus
      followed by an infusion of 35 mg over 60 minutes; abciximab iv bolus of 0.25
      mg/kg followed by a 12 h infusion of 0.125 microg/kg per minute; unfractionated
      heparin). At baseline angiographic examination revealed no flow (TIMI 0+1) in the
      infarct-related artery in 17.1% of patients, impaired flow (TIMI 2) in 17.1% and
      normal (TIMI 3) in 65.8% of cases. After immediate PCI, a significant improvement
      in epicardial perfusion (TIMI 2+3, 99.5%) and in microcirculation was achieved.
      This favourable effect was seen only in the group of patients with baseline TIMI
      0+1 flow, whereas PCI in the group with baseline TIMI 3 flow did not cause any
      further improvement in microcirculatory perfusion. The rate of cardiovascular
      events within the first 30 days and 12 months after the procedures were similar
      in the studied subgroup of patients. CONCLUSIONS: PCI performed after combined
      fibrinolytic therapy in STEMI patients is associated with high efficacy and
      improvement in indices of epicardial perfusion and microcirculation. These
      benefits are confined mainly to patients with primarily impaired flow in the
      infarction-related artery (TIMI 0+1). However, the clinical results of this
      strategy, particularly in patients undergoing PCI following successful combined
      fibrinolytic therapy, must still be proved in further randomised trials.

PMID- 16583325
TI  - Diagnostic utility of tissue tracking echocardiography for the diagnosis of
      ischaemic heart disease.
AB  - INTRODUCTION: Both the resting electrocardiogram and standard echocardiography
      have limited value in detecting ischaemic heart disease (IHD) in patients with
      atypical symptoms or asymptomatic subjects. Tissue tracking (TT) is a novel
      method based on tissue Doppler echocardiography for the assessment of
      longitudinal apical myocardial motion. AIM: To assess diagnostic utility of TT
      mode in the diagnosis of IHD. METHODS: The study was performed in a group of 36
      patients (aged 58+/-8 years, 15 males) with good acoustic window, sinus rhythm
      and normal left ventricular ejection fraction on standard echocardiography who
      were previously selected for coronary angiography. Systolic displacement of
      myocardium (TT) was assessed in all patients using apical views (4, 2, and 3
      chamber) and 7-colour-coded visualisation expressing various apical displacements
      of the myocardium during systole. Group IHD(-) consisted of 16 patients with
      normal coronary angiography or insignificant lesions and group IHD(+) consisted
      of 20 patients with significant (>70%) coronary lesions. RESULTS: Despite similar
      prevalence of arterial hypertension and diabetes as well as similar
      pharmacological treatment patients from the IHD(+) group had a lower TT index
      (ratio of the sum of regional TT values to the number of analysed segments than
      the IHD(-) (patients 4.5+/-0.8 mm vs 5.9+/-0.9 mm respectively, p <0.001).
      CONCLUSIONS: Resting echocardiography with tissue tracking enables fast, non
      invasive and semiquantitative evaluation of left ventricular function. This
      method of assessment of longitudinal layers of the left ventricle may be useful
      in the diagnosis of ischaemic heart disease.

PMID- 16583327
TI  - Local paclitaxel delivery as a treatment of persistent, recurrent in-stent
      restenosis -- safety assessment.
AB  - INTRODUCTION: In-stent restenosis still remains a serious clinical problem. Local
      intramural drug delivery (LDD -- Local Drug Delivery) seems to be an interesting
      alternative to drug-eluting stents (DES). AIM: The aim of the study was to assess
      the safety and effectiveness of local intramural paclitaxel administration in the
      treatment of recurrent in-stent restenosis (ISR). METHODS: Five patients were
      enrolled in the study (3 men, mean age 50+/-7 years) with at least a second
      episode of ISR within the same stent. Percutaneous coronary angioplasty was
      performed on a total of 11 vessel segments. Remedy delivery catheters (Boston
      Scientific) were used for balloon angioplasty. Inflation pressure was calibrated
      to obtain a balloon/vessel lumen ratio of 1.1:1. Then the pressure was lowered to
      3 atmospheres and 100 microg of paclitaxel diluted in 2 ml of 0.9% NaCl was given
      over 60 seconds under the pressure of 2-3 atmospheres. This dose was used for
      each 10 mm of lesions. Control coronary angiography was performed six months
      after the procedure. RESULTS: In all patients effective target vessel
      revascularisation was achieved. No adverse events were observed in the
      periprocedural period or during the 6-month follow-up period. Control angiography
      revealed ISR in three segments (27.2%) and in-stent late lumen loss of 0.21+/
      0.93 mm. CONCLUSIONS: Local intramural paclitaxel delivery is a safe and
      effective method of ISR treatment. The optimal paclitaxel dose should be
      established in further studies.

PMID- 16583329
TI  - "Tombstoning" of ST segment in acute myocardial infarction -- effect on clinical
      course.
AB  - INTRODUCTION: There are many reports evaluating the effects of the amplitude of
      ST segment elevation in acute myocardial infarction with ST segment elevation
      (STEMI) on infarction zone and course. There are, however, few publications
      dealing with the effects of ST segment elevation shape in STEMI patients on their
      clinical course and prognosis. AIM: Assessment of the rate of "tombstoning" of ST
      segment (TOMB-ST) in STEMI patients and the effects on their clinical outcome.
      METHODS: The study involved 207 consecutive patients with STEMI hospitalised in
      the period 2000-2002 analysed with respect to the in-hospital complication rate.
      RESULTS: On admission, TOMB-ST was observed in 55 (26.1%) subjects. TOMB-ST was
      more common in anterior MI (39.8%) than in inferior MI (10.6%). Patients with
      TOMB-ST compared to non-TOMB-ST ones had a significantly higher mortality rate
      (38.2% vs 9.9%, p <0.001), heart failure (45.6% vs 28.3%, p <0.026), ventricular
      fibrillation (18.1% vs 6.4%, p <0.016), and lower left ventricular ejection
      fraction (40.9% vs 48.6%, p <0.001). The sum of amplitudes of ST segment
      deviations (SigmaST) >20 mm was indicative for the subgroup of patients with TOMB
      ST and trend towards higher mortality (40% vs 30%, NS). However, in patients
      without TOMB-ST, SigmaST >20 mm identified two subgroups with significantly
      different mortality rates (20% vs 4%, p=0.001). CONCLUSIONS: TOMB-ST was observed
      in one fourth of patients with STEMI. This abnormality was associated with an
      increased mortality rate, higher incidence of heart failure and ventricular
      fibrillation as well as decreased left ventricular ejection fraction. In the
      population with TOMB-ST, increased mortality was independent of the total
      amplitude of ST segment displacement; this relation was, however, observed in
      patients with STEMI without TOMB-ST.

PMID- 16583331
TI  - [Management of patients after valvular heart surgery. Guidelines of the European
      Cardiologic Society].

PMID- 16583333
TI  - [Surgical treatment of interventricular septum rupture in an 87-year-old female
      with acute antero-lateral myocardial infarction and 97% risk according to the
      Euroscore scale].
AB  - Rupture of the interventricular septum is a serious complication of myocardial
      infraction (MI). It occurs in 1-3% of all MI cases, usually within 2 weeks after
      infraction. In 60% of the cases post-MI ventricular septal defects (VSD) are the
      result of completely occluded coronary artery supplying anterior wall of left
      ventricle and subsequent transmural MI. 50% of patients die within the first week
      after the rupture unless they are surgically treated. In this case report we
      describe an 87-year-old woman with post-MI VSD who was successfully operated
      (endocardial patch exclusion technique, proposed by David). In spite of a very
      high predicted risk (97% by Euroscore), calculated high risk should not be
      considered as the contraindication for life-saving operation.

PMID- 16583335
TI  - [Thrombus in the left atrium -- is it always treated properly?].
AB  - A case of a 61-year-old female with a history of stroke in a course of mitral
      stenosis with atrial fibrillation is reported. Mitral commissurotomy was
      conducted eight years after the diagnosis. The chest X-ray revealed large
      calcified mass in the left atrium. During surgical mitral valve replacement the
      mass has been removed and identified as calcified thrombus. Despite numerous risk
      factors, anticoagulation has not been introduced until a few months before the
      operation.

PMID- 16583336
TI  - [Myocardial infarction after butane inhalation in a 14-year-old boy].
AB  - Myocardial infarction is a rare disease in children. Among many reasons the toxic
      damage of myocardium should be taken into consideration. The authors present the
      case of a 14-year-old boy with sudden cardiac arrest due to ventricular
      fibrillation and myocardial infarction as a result of butane gas inhalation.
      Coronary angiography revealed normal coronary arteries. Cardioverter
      defibrillator was implanted as a secondary prophylaxis of sudden cardiac death.

PMID- 16583337
TI  - [Cardiac tamponade in a neonate with cardiac tumour].
AB  - A case of a neonate with a life-threatening cardiac tamponade due to cardiac
      tumour is presented. Pericardiocentesis was performed and 300 ml of purulent
      fluid was evacuated. Pericardial drainage was undertaken. Six months later
      cardiac tamponade recurred and was again successfully treated with pericardial
      drainage. A subsequent 10-month follow-up was uneventful. Diagnosis and treatment
      of cardiac tumours associated with pericardial effusion are discussed.

PMID- 16583339
TI  - [Physical training improves orthostatic tolerance. Patterns of physical activity
      that are useful in prevention of vasovagal syncope].

PMID- 16583338
TI  - [Cardiac tamponade as the first symptom of oesophageal carcinoma -- a case
      report].
AB  - We present a case of a 56-year-old male who was admitted to our hospital due to
      cardiac tamponade. A 600 ml of purulent fluid was evacuated from the pericardium.
      The patient received antibiotics, however, due to recurrent pericardial effusion
      a pericardial drainage was required. Esophagoscopy and computerised tomography
      revealed oesophageal carcinoma with oesophago-pericardial fistula.

PMID- 16583340
TI  - [The PPARgamma receptor agonists and prevention of cardio-vascular complications
      in patients with type 2 diabetes. The results of the PROactive study].

PMID- 16583341
TI  - [ST segment elevation in "non-atherosclerotic" myocardial infarction].

PMID- 16583342
TI  - [Giant aneurysm of the descending aorta mimicking extracardiac mass].
AB  - The case report presents a giant aneurysm of the descending aorta in a 79- year
      old female. The echocardiographic study of the patient was substantially impeded,
      since aortic pathology obscured the left atrium in standard views and produced
      images mimicking extracardiac mass. Modified imaging planes were necessary to
      complete the correct echocardiographic visualisation of the heart and the aorta
      and to establish diagnosis.

PMID- 16583343
TI  - [Gastrointestinal bleeding in a patient with acute myocardial infarction treated
      with primary coronary angioplasty and abciximab (ReoPro) administration].

PMID- 16583344
TI  - [Ventricular fibrillation in a patient with three accessory pathways, Ebstein
      anomaly and intermittent long QT interval. RF ablation and electrophysiologic
      considerations].
AB  - We present a case of a 19-year old man with minor Ebstein's anomaly, intermittent
      long QT interval and WPW syndrome in whom atrial fibrillation, degenerating into
      ventricular fibrillation was the first symptom. QRS complex morphologies during
      atrial fibrillation revealed the presence of three accessory pathways (septal,
      right inferior paraseptal and antero-inferior). Immediately after resuscitation
      the patient was treated with amiodarone, which resulted in a significant
      prolongation of QT interval to 700 ms. After RF ablation of accessory pathways
      patient remains asymptomatic during 6-month follow up, however QTc interval is
      about 500 ms.

PMID- 16583345
TI  - [Interventional cardiology role in the expansion of peripheral endovascular
      interventions. The crucial need for inter specialty collaboration].

PMID- 16583346
TI  - [Online-consulting for eating disorders--analysis of users and contents].
AB  - OBJECTIVE: Since 1998, the online information and consulting server for patients
      with eating disorders and their relatives (www.ab-server.de) offers an online
      consulting service. METHODS: 2176 e-mails were qualitatively and quantitatively
      analysed. RESULTS: The symptom descriptions refer mostly to bulimia nervosa
      (63.1%). People mainly asked for behaviour patterns in dealing with the illness
      or with an affected person (33.3%) as well as for information about the illness
      (18.7%). CONCLUSIONS: The low threshold and professional online consulting
      service is highly accepted by the target group.

PMID- 16583348
TI  - [For: "Every person with schizophrenia should be treated as early as possible"].

PMID- 16583347
TI  - [Rehabilitation of the mentally ill].

PMID- 16583349
TI  - [Prevention of alcoholism: what are effective strategies?].
AB  - OBJECTIVE: This review provides information about the current state of knowledge
      concerning alcohol prevention. METHODS: The most important prevention strategies
      are presented along with data about their efficacy. RESULTS: At present, the
      results of the available international research literature suggest, that the most
      effective strategies are taxation and price increases and the restriction of the
      purchase of alcohol. There is also positive evidence for interventions at the
      workplace and in the primary care system. CONCLUSIONS: To positively influence
      attitudes towards drinking before alcohol-associated problems are evident seems
      to be much more difficult, new approaches are necessary.

PMID- 16583350
TI  - [Early termination of vocational rehabilitation for the severe mentally ill].
AB  - OBJECTIVE: To determine the conditional factors underlying a premature
      termination of vocational rehabilitation programs. METHODS: 123 rehabilitation
      participants were assessed prospectively regarding sociodemographic and
      psychopathological variables, level of functioning, subjective health,
      intellectual and work capacity. RESULTS: 23 persons terminated rehabilitation
      prematurely. Drop-outs differed regarding sociodemographic and illness-related
      variables, in subjective physical health, level of functioning, intelligence and
      work capacity. Three types of "drop-outs" could be identified: Termination due to
      exacerbation (of a functional psychosis), due to reluctance to show-up (mainly
      men with antisocial personality disorders) and a non-specific group. CONCLUSION:
      Vocational rehabilitation of subjects with severe mental illness should take
      account of each rehabilitant's individual capacities and abilities as well as
      individual concepts of the disorder. Moreover, integrated concepts of medical
      treatment and vocational rehabilitation are needed to ensure rehabilitation
      success.

PMID- 16583351
TI  - [Media coverage on suicide in Nuremberg's daily papers--frequency and form of the
      reporting before and during media-intervention with guidelines].
AB  - BACKGROUND: As one of its suicide preventive actions, the "Nuremberg Alliance
      Against Depression" has started cooperation with local media in 2001 by
      implementing a 14-item-mediaguide concerning a more sensible way of suicide
      reporting to prevent copy-cat suicides. The effects of this mediaguide on the
      reporting are being evaluated. METHODS: A systematic recording of all suicide
      reports during 2000 (Baseline) and 2001 (first intervention year) was performed
      for three regional dailies in Nuremberg. A comparison of the reporting regarding
      the frequency, distribution and some qualitative aspects between baseline and
      intervention year as well as to a control-medium from Wurzburg was carried out.
      RESULTS: Two out of three dailies in Nuremberg show a noticeable reduction in the
      numbers of articles on suicides. Compared to the baseline and control-medium one
      of the decreases is statistically significant. The results of the third
      newspaper, however, indicated an opposite direction, stating a significant
      increase in the number of reports. CONCLUSIONS: Crucial criterion for a
      mediaguide's favourable influence on the suicide-reporting is the willingness of
      the main editors in charge at the local dailies to be engaged and willing to
      cooperate. This can be achieved only through good personal contact and
      relationship to the project.

PMID- 16583352
TI  - [Associations between dementia and head circumference as a measure of brain
      reserve--results from the Bavarian School sisters study].
AB  - OBJECTIVE: The aim of the study was to examine the relationship of head
      circumference as a marker of maximal attained brain size to late-life cognitive
      impairment and dementia. METHODS: Cognitive performance was assessed and the
      presence of dementia was diagnosed in a cross-sectional study of 442 Catholic
      sisters aged 65 years and over. RESULTS: A head circumference below average was
      significantly associated with the presence of dementia even after adjustment for
      age, body mass index and presence of one or two apolipoprotein E epsilon4 alleles
      (OR = 2.0; 95% CI: 1.1-3.6). The combination of small head circumference and
      apolipoprotein E epsilon4 strongly increased the risk of dementia (OR = 3.59; 95%
      CI: 1.44-8.97). CONCLUSIONS: The findings support the hypothesis that a larger
      head size reduces the risk of cognitive decline and dementia in old age.

PMID- 16583353
TI  - [Is primary prevention of mental illness possible?].

PMID- 16583354
TI  - NEMO binding domain of IKK-2 encompasses amino acids 735-745.
AB  - NF-kappaB activation is mediated by the IKK signalsome. Though this signalsome is
      comprised of IKK-1, IKK-2, and NEMO/IKKgamma, it is the interaction between IKK-2
      and NEMO that is critical to formation of a functional signalsome. More
      specifically, previous reports have indicated that this interaction involves the
      C-terminal LDWSWL residues of IKK-2 (called the Nemo Binding Domain (NBD)) and
      the N-terminus of NEMO. In an effort to characterize the IKK-2:NEMO interaction,
      we have investigated several NBD-containing peptides for their ability to bind
      NEMO and inhibit the critical IKK-2:NEMO interaction. The six residue NBD
      peptide, LDWSWL, showed modest binding to NEMO and little inhibition of the IKK
      2:NEMO interaction, whereas peptides containing the NBD plus additional flanking
      amino acids (NBD-containing peptides) more effectively bound NEMO and inhibited
      the interaction. These longer NBD-containing peptides may be required to give the
      NBD an appropriate conformation for recognition by NEMO and/or to provide for
      additional interactions with NEMO.

PMID- 16583356
TI  - High-level expression, activation, and subcellular localization of p38-MAP kinase
      in thyroid neoplasms.
AB  - The p38 family of MAP kinases (p38-MAPKs) is involved in regulating the
      proliferation, survival, and migration of various cancer cells. The present study
      has investigated the expression, subcellular localization, phosphorylation, and
      activity of p38-MAPKs in normal and tumoural human thyroid tissues and in thyroid
      cell lines. The expression and nucleo-cytosolic compartmentalization of the alpha
      isoform of p38-MAPKs (p38alpha-MAPK) were studied by western blotting in the WRO
      and B-CPAP cell lines, which are derived from human follicular and papillary
      thyroid carcinomas, respectively, and in the non-transformed rat thyroid cell
      lines FRTL-5 and PCCL3. Immunohistochemistry was used to study the expression and
      subcellular localization of p38alpha-MAPK, and of the phosphorylated forms of p38
      MAPKs (P-p38-MAPKs) in human toxic adenomas (TAs), follicular adenomas (FAs),
      papillary thyroid carcinomas (PTCs), and follicular thyroid carcinomas (FTCs).
      The activity of p38-MAPKs in PTCs and FTCs was revealed by immunohistochemical
      detection of their typical phosphorylated substrate, MAPK-activated protein
      kinase 2/3 (MK2/3). p38alpha-MAPK was expressed in all cell lines and this
      expression was restricted to the cytosolic compartment. p38 MAPK activity was
      involved in regulating DNA synthesis in B-CPAP cells. p38alpha-MAPK and P-p38
      MAPKs were strongly expressed in PTC and FTC cells, although only in the
      cytoplasm, whereas they were only very weakly expressed in FA cells, and absent
      in adjacent normal tissues. They were also expressed at a high level in TAs, but
      they were found in both nucleus and cytoplasm. Finally, phospho-MK2/3
      immunostaining followed very similar patterns to those of p38alpha-MAPK and P-p38
      MAPKs in PTCs and FTCs. Taken together, these results show for the first time
      that the p38-MAPK signalling cascade is functional in two types of differentiated
      carcinoma of the thyroid. The observation that p38-MAPK hyper-expression occurs
      in FTC, but not in FA, may provide an additional diagnostic tool for malignancy
      in some thyroid nodules.

PMID- 16583355
TI  - DC-SIGN association with the Th2 environment of lepromatous lesions: cause or
      effect?
AB  - The clinical spectrum of leprosy is related to patients' immune responses. Non
      responsiveness towards Mycobacterium leprae (ML) seems to correlate with a Th2
      cytokine profile. The reason for such a polarized immune response remains
      unclear. The C-type lectin, DC-SIGN, expressed by subsets of dendritic cells
      (DCs) and macrophages, has previously been associated with Th2 responses. Here we
      show abundant DC-SIGN expression in lepromatous but not borderline tuberculoid
      leprosy, in both HIV-positive and HIV-negative patients. Moreover, we demonstrate
      that DC-SIGN can act as an entry receptor for ML, as it does for M. tuberculosis,
      through the cell wall component lipoarabinomannan. DC-SIGN is expressed on
      virtually all ML-containing cells, providing further evidence for its role as a
      receptor. DC-SIGN may therefore be induced on macrophages in lepromatous leprosy
      and may then contribute to mycobacterial entry into these cells.

PMID- 16583357
TI  - Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in nasal polyps
      of patients with aspirin-intolerant asthma.
AB  - In aspirin-intolerant subjects, adverse bronchial and nasal reactions to
      cyclooxygenase (COX) inhibitors are associated with over-production of cysteinyl
      leukotrienes (cys-LTs) generated by the 5-lipoxygenase (5-LO) pathway. In the
      bronchi of patients with aspirin-intolerant asthma, we previously linked cys-LT
      over-production and aspirin hyper-reactivity with elevated immunoexpression in
      eosinophils of the terminal enzyme for cys-LT production, LTC4 synthase. We
      investigated whether this anomaly also occurs in the nasal airways of these
      patients. Immunohistochemical expression of 5-LO and COX pathway proteins was
      quantified in nasal polyps from 12 patients with aspirin-intolerant asthma and 13
      with aspirin-tolerant asthma. In the mucosa of polyps from aspirin-intolerant
      asthmatic patients, cells immunopositive for LTC4 synthase were four-fold more
      numerous than in aspirin-tolerant asthmatic patients (p=0.04). There were also
      three-fold more cells expressing 5-LO (p=0.037), with no differences in 5-LO
      activating protein (FLAP), COX-1 or COX-2. LTC4 synthase-positive cell counts
      correlated exclusively with mucosal eosinophils (r=0.94, p<0.001, n=25). Co
      localisation confirmed that five-fold higher eosinophil counts (p=0.007)
      accounted for the increased LTC4 synthase expression in polyps from aspirin
      intolerant asthmatic patients, with no alterations in mast cells or macrophages.
      Within the epithelium, increased counts of eosinophils (p=0.006), macrophages
      (p=0.097), and mast cells (p=0.034) in aspirin-intolerant asthmatic polyps were
      associated only with 2.5-fold increased 5-LO-positive cells (p<0.05), while the
      other enzymes were not different. Our results indicate that a marked over
      representation of LTC4 synthase in mucosal eosinophils is closely linked to
      aspirin intolerance in the nasal airway, as in the bronchial airways.

PMID- 16583358
TI  - Endomyocardial infiltration by B and NK cells foreshadows the recurrence of
      cardiac allograft rejection.
AB  - Heart allograft outcome is unpredictable and acute rejection episodes still occur
      despite the improvement of immunosuppressive regimens. We therefore investigated
      whether the immunopathological profile of endomyocardial biopsies might underlie
      the variations in the clinical course of a graft. Biopsies from transplanted
      patients were analysed by histology, immunohistochemistry (associated with
      digital image analysis), confocal and electron microscopy to determine the type
      and the functional state of leukocytes infiltrating the myocardium, together with
      their ultrastructural features and those of the graft itself. In comparison with
      biopsies with grade 0R or grade 1R rejection, those from patients with grade 2R
      rejection displayed significant infiltration of macrophages, T lymphocytes, and
      CD83+ and DC-SIGN+ dendritic cells. Fifty-seven per cent were invaded by CD20+B
      lymphocytes, most of which expressed CD69 activation marker and cooperated in
      interleukin-12 production, and by CD69+CD94+NK cells expressing interferon-gamma.
      Ultrastructural signs of myocyte degeneration and microvessel rupture by NK cells
      were frequent. These patients developed recurrent episodes of acute allograft
      rejection. Endomyocardial B and NK infiltrates are involved in the dynamics of
      allograft rejection and are associated with a high risk of its recurrence.
      Immunopathological assessment of endomyocardial biopsies may thus serve to
      forecast the probable outcome of a heart allograft.

PMID- 16583359
TI  - A marginal zone phenotype in follicular lymphoma with t(14;18) is associated with
      secondary cytogenetic aberrations typical of marginal zone lymphoma.
AB  - Marginal zone differentiation of follicular lymphomas (FL), sometimes referred to
      as monocytoid B-cell differentiation, is a relatively uncommon phenomenon.
      Recently, this type of differentiation was also linked to secondary cytogenetic
      aberrations of chromosome 3 in a small number of patients. We have analysed 131
      primary nodal FL with t(14;18)(q32;q21) for secondary cytogenetic aberrations
      previously described as recurrent in marginal zone lymphomas (MZL) to identify
      their frequency and possible association with morphological evidence of marginal
      zone differentiation. We searched for trisomy of chromosomes 3, 12, and 18, gains
      of chromosome arm 3q, deletions of chromosome arm 7p, structural anomalies with
      break-points in 1q21 and 1p34, as well as the t(1;2)(p22;p12), t(1;14)(p22;q32),
      t(3;14)(q27;q32), t(6;14)(p21;q32), and t(11;18)(q21;q21) translocations. At
      least focal morphological evidence of marginal zone differentiation occurred in
      35/131 (27%) FL with t(14;18)(q32;q21) as the primary chromosomal abnormality.
      None of the recurrent balanced translocations characteristic of extranodal MZL
      were seen secondarily in the nodal FLs with t(14;18)(q32;q21). However, 43/131
      (33%) cases had at least one of the above secondary cytogenetic aberrations
      previously reported as recurrent aberrations in MZL and, when combined, these
      were significantly more frequent in FL with morphological evidence of marginal
      zone differentiation (p<0.0001, two-sided Fisher's exact test). Aberrations of
      chromosome 3 and, in particular, trisomy 3 occurred frequently in FL with
      marginal zone differentiation (p=0.002 and p<0.0001, respectively, two-sided
      Fisher's exact test), while chromosome 21, 22, and X chromosome aberrations,
      which have not been described previously as recurrent in MZL, were also
      significantly associated with marginal zone differentiation in FL (p=0.002,
      p=0.037, p=0.039, respectively, two-sided Fisher's exact test).

PMID- 16583360
TI  - Gastrointestinal stromal tumours overexpress fatty acid synthase.
AB  - Fatty acid synthase (FASN), a key enzyme for de novo lipogenesis, is
      overexpressed in many malignant tumours and is associated with aggressive
      biological behaviour. FASN expression and its possible relationship with more
      aggressive behaviour in gastrointestinal stromal tumours (GISTs) have not been
      addressed to date. Here, FASN expression was assessed by immunohistochemistry in
      60 primary GISTs (28 low/intermediate risk and 32 high risk) and seven metastatic
      GISTs. Sixteen smooth muscle gastrointestinal tumours were used as controls. FASN
      was overexpressed in 36 of 60 GISTs (60%): in 12 of 28 (42%) low/intermediate
      risk GISTs and in 24 of 32 (75%) high-risk GISTs (p<0.05). Two primary and seven
      metastatic GISTs and five GIST cell lines (GIST882, GIST430, GIST522, GIST62, and
      GIST48), analysed by western blot, showed variable FASN expression. Most
      metastatic samples expressed high levels of FASN protein. Additionally, seven of
      60 GISTs showed a proliferation rate higher than 10% by Ki67 and all of them
      expressed FASN (p<0.04). Finally, proliferation and apoptosis were investigated
      after FASN silencing in GIST882 cells, which displayed the highest FASN
      expression. siRNA-mediated FASN knock-down inhibited expression of the
      proliferation marker cyclin A, whereas no changes in p27 and cleaved PARP
      expression were seen. It is concluded that FASN is preferentially overexpressed
      in high-risk and metastatic GISTs, and that its overexpression likely contributes
      to cell proliferation.

PMID- 16583361
TI  - Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in
      different geographical regions.
AB  - Infectious agents play a critical role in MALT lymphoma development. Studies from
      Italy showed Chlamydia psittaci infection in 87% of ocular adnexal MALT lymphomas
      and complete or partial regression of the lymphoma after C. psittaci eradication
      in four of nine cases. However, C. psittaci was not demonstrated in ocular
      adnexal MALT lymphomas from the USA. This study was thus designed to investigate
      further the role of C. psittaci, and other infectious agents commonly associated
      with chronic eye disease, in the development of ocular adnexal MALT lymphoma. The
      presence of C. psittaci, C. trachomatis, C. pneumoniae, herpes simplex virus 1
      and 2 (HSV1, HSV2), and adenovirus 8 and 19 (ADV8, ADV19) was assessed separately
      by polymerase chain reaction in 142 ocular adnexal MALT lymphomas, 53 non
      marginal zone lymphomas, and 51 ocular adnexal biopsies without a
      lymphoproliferative disorder (LPD), from six geographical regions. C. psittaci
      was detected at similar low frequencies in non-LPD and non-marginal zone lymphoma
      groups from different geographical regions (0-14%). Overall, the prevalence of C.
      psittaci was significantly higher in MALT lymphomas (22%) than in non-LPD (10%,
      p=0.042) and non-marginal zone lymphoma cases (9%, p=0.033). However, the
      prevalence of C. psittaci infection in MALT lymphoma showed marked variation
      among the six geographical regions examined, being most frequent in Germany
      (47%), followed by the East Coast of the USA (35%) and the Netherlands (29%), but
      relatively low in Italy (13%), the UK (12%), and Southern China (11%). No
      significant differences in the detection of C. pneumoniae, C. trachomatis, HSV1,
      HSV2, ADV8, and ADV19 were found between lymphomas and controls from different
      geographical regions. In conclusion, our results show that C. psittaci, but not
      C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8 or ADV19, is associated with
      ocular adnexal MALT lymphoma and that this association is variable in different
      geographical areas.

PMID- 16583362
TI  - Dissecting intramyocardial hematoma masquerading as a pseudoaneurysm of left
      ventricular free wall: an unusual case of myocardial rupture.
AB  - This report presents a case of left ventricular intramyocardial dissection
      masquerading as a ventricular pseudoaneurysm. Only serial echocardiograms could
      lead to the correct diagnosis, and left ventricular angiography could
      appropriately direct further testing and treatment.

PMID- 16583364
TI  - Motivation and synthesis of the FIAC experiment: Reproducibility of fMRI results
      across expert analyses.
AB  - The Functional Imaging Analysis Contest (FIAC) culminated in the FIAC Workshop
      held at the 11th Annual Meeting of the Organization for Human Brain Mapping in
      Toronto in 2005. This special issue summarizes various analyses used by
      contestants with a single functional magnetic resonance imaging (fMRI) study, a
      cortical-language study using sentence repetition. The results from the cognitive
      neuroscientists who developed the test-base language study, and report their data
      analysis, are complemented by expert analyses of the same test-base data by most
      of the major groups actively developing fMRI software packages. Analyses include
      many variants of the general linear model (GLM), cutting-edge spatial- and
      temporal-wavelets, permutation-based, and ICA approaches. A number of authors
      also include surface-based approaches. Several articles describe the important
      emerging areas of diagnostics for GLM analysis, multivariate predictive modeling,
      and functional connectivity analysis. While the FIAC did not achieve all of its
      goals, it helped identify new activation regions in the test-base data, and more
      important, through this special issue it illustrates the significant methods
      driven variability that potentially exists in the literature. Variable results
      from different methods reported here should provide a cautionary note and
      motivate the Human Brain Mapping community to explore more thoroughly the
      methodologies they use for analyzing fMRI data.

PMID- 16583365
TI  - Denervation hypertrophy may mimic local tumor spread on magnetic resonance
      imaging.
AB  - We report a patient with an extensive paranasal sinus carcinoma. One year after
      tumor resection, magnetic resonance imaging (MRI) showed swelling of the
      ipsilateral masticatory muscles with signal increase on T2-weighted images and
      gadolinium-DTPA uptake, suggestive of local tumor infiltration. However,
      electromyography, biopsy, and follow-up MRI confirmed denervation
      pseudohypertrophy of the muscles innervated by the mandibular nerve and excluded
      tumor recurrence. Muscle denervation and pseudohypertrophy should be considered
      in the differential diagnosis of appropriate patients with suspected tumor
      recurrence.

PMID- 16583366
TI  - Assessment of muscle fatigue during exercise in chronic obstructive pulmonary
      disease.
AB  - Contractile fatigue is associated with exercise intolerance in patients with
      chronic obstructive pulmonary disease (COPD). Contractile fatigue may be assessed
      by quantifying the decline in strength after a fatiguing protocol but this may
      pose practical problems. The purpose of this study was to investigate the
      relationship between the decline in quadriceps strength, quadriceps electrical
      activity, perception of leg fatigue, and arterial lactate level in patients with
      COPD during constant work-rate cycling exercise. The decline in quadriceps
      strength was significantly associated with the decrease in electromyographic
      median frequency (r = 0.606), leg fatigue perception (r = 0.453), and arterial
      lactate level (r = 0.384). Using the receiver-operating-characteristic curve, it
      was found that a 4% decline in electromyographic median frequency had a 94%
      sensitivity and a 75% specificity to predict contractile fatigue. We conclude
      that contractile fatigue commonly occurs during cycling exercise in COPD. The
      electromyographic median frequency appears to be a valuable indirect marker to
      predict contractile leg fatigue.

PMID- 16583367
TI  - Oxidative stress and antioxidant enzyme upregulation in SOD1-G93A mouse skeletal
      muscle.
AB  - Amyotrophic lateral sclerosis (ALS) is caused by motor neuron loss in the spinal
      cord, but the mechanisms responsible are not known. Ubiquitous transgenic
      overexpression of copper/zinc superoxide dismutase (SOD1) mutations causing
      familial ALS (SOD1mut) leads to an ALS phenotype in mice; however, restricted
      expression of SOD1mut in neurons alone is not sufficient to cause this phenotype,
      suggesting that non-neuronal SOD1mut expression is also required for disease
      manifestation. Recently, several investigators have suggested that SOD1mut 
      mediated oxidative stress in skeletal muscle may contribute to ALS pathogenesis.
      The purpose of this study was to examine oxidative stress and antioxidant enzyme
      adaptation in 95-day-old SOD1-G93A skeletal muscle. We observed significant
      elevations in both malondialdehyde (22% and 31% in red and white gastrocnemius,
      respectively) and protein carbonyls (53% in red gastrocnemius) in SOD1-G93A mice.
      Copper/zinc SOD activity was higher in red and white SOD1-G93A gastrocnemius (7-
      and 10-fold, respectively), as was manganese SOD (4- and 5-fold, respectively)
      and catalase (2- and 2.5-fold, respectively). Taken together, our data
      demonstrate oxidative stress and compensatory antioxidant enzyme upregulation in
      SOD1-G93A skeletal muscle.

PMID- 16583368
TI  - Mycophenolate mofetil and tacrolimus: new therapeutic options in
      neuroimmunological diseases.
AB  - Mycophenolate mofetil (MMF) and tacrolimus are novel immunosuppressive drugs,
      both first established in transplantation medicine and now used increasingly in
      neuroimmunological diseases including myasthenia gravis, dysimmune
      polyneuropathies, and myositis. In myasthenia gravis, the efficacy and safety of
      MMF has been shown by one open-label trial; one small, double-blind, placebo
      controlled trial; and a few retrospective analyses. Similarly, for tacrolimus the
      greatest experience and evidence for efficacy and safety have been gathered in
      myasthenia gravis. MMF and tacrolimus have both been used as an alternative
      treatment for various other autoimmune diseases in which azathioprine or
      cyclosporine were not sufficiently effective. However, experience with tacrolimus
      in dysimmune polyneuropathies and myositis is limited. At this time, the
      available data suggest that MMF and tacrolimus are well suited for long-term
      immunosuppression in patients with myasthenia gravis. The spectrum of
      neuroimmunological diseases in which these drugs may be used has not been finally
      delineated and will require further controlled studies.

PMID- 16583369
TI  - Single-fiber electromyography shows terminal axon dysfunction in Miller Fisher
      syndrome: a case report.
AB  - We studied a patient with ophthalmoparesis and pupillary areflexia 2 weeks after
      a viral syndrome. Miller Fisher syndrome was suspected but GQ1b antibodies were
      not detected. To define neuromuscular involvement we performed electrodiagnostic
      studies. Single-fiber electromyography (SFEMG) in the extensor digitorum communis
      (EDC) showed abnormal jitter and axonal blocking, suggesting terminal axon
      dysfunction. Subsequent GQ1b antibody titers were elevated to borderline levels.
      Clinical symptoms gradually resolved. SFEMG may help characterize neuropathies
      associated with antibodies to neuronal ganglioside and identify involvement of
      the terminal axon and neuromuscular junction.

PMID- 16583370
TI  - Botulinum toxin improves sialorrhea and quality of living in bulbar amyotrophic
      lateral sclerosis.
AB  - Sialorrhea is frequently a socially disabling symptom in patients with bulbar
      amyotrophic lateral sclerosis (ALS). In this open-label prospective study, we
      report the effect of botulinum toxin A (Botox) injection into the parotid glands
      in 10 patients with bulbar ALS and socially disabling sialorrhea. We applied
      three different outcome measures to determine the effect of Botox therapy on
      sialorrhea. Botox significantly improved the degree of sialorrhea and a drooling
      impact score and, by inference, the quality of living, in over half of the
      patients with bulbar ALS and severe sialorrhea. The beneficial effect of Botox
      lasted for at least 2 months in those who responded. No major adverse effects
      were noted. Local injection of a small dose of Botox into the parotid glands can
      control sialorrhea and potentially improve living quality in some patients with
      bulbar ALS.

PMID- 16583371
TI  - Persistent increased risk for thymoma in myasthenia gravis associated with
      myositis.

PMID- 16583372
TI  - Evidence for MHC-1-restricted CD8+ T-cell-mediated immunopathology in canine
      masticatory muscle myositis and polymyositis.

PMID- 16583374
TI  - Enzyme replacement therapy and intraepidermal innervation density in Fabry
      disease.
AB  - We prospectively evaluated the effect of enzyme replacement therapy (ERT) on the
      intraepidermal nerve fiber density (IENFD) and thermal threshold in patients with
      Fabry disease, an X-linked disorder associated with a painful small-fiber
      neuropathy and decreased linear IENFD in a length-dependent pattern. Twenty-five
      hemizygous male patients with Fabry disease were enrolled in a 6-month,
      randomized, placebo-controlled ERT trial of 0.2 mg/kg of alpha-galactosidase A
      (agalsidase-alfa) every 2 weeks followed by an additional 12 months of open-label
      ERT for both populations. IENFD and thermal threshold were measured in the distal
      thigh at baseline, 6 months, and 18 months from initiation of the trial. We found
      no significant difference in IENFD between the treatment groups at 6 months.
      After an additional year of ERT, there was a significant reduction in IENFD in
      the patient group as a whole, attributable to the declining glomerular filtration
      rate. Thermal thresholds remained unchanged. We conclude that epidermal nerve
      fiber regeneration, as measured in the distal thigh, does not occur in this
      patient population after 12-18 months of ERT.

PMID- 16583375
TI  - Frequency-dependent conduction block in carpal tunnel syndrome.

PMID- 16583378
TI  - Psychologically meaningful activity, illness intrusiveness, and quality of life
      in rheumatic diseases.

PMID- 16583376
TI  - Secretory products of central nervous system glial cells induce Schwann cell
      proliferation and protect from cytokine-mediated death.
AB  - There continues to be interest in Schwann cells (SC) as a possible source of
      myelinating cells for transplantation into the central nervous system (CNS) of
      patients with multiple sclerosis (MS) and spinal cord injury. It has been
      suggested that CNS glial cells interfere with SC migration, survival, maturation,
      and clinically significant remyelination in the CNS. To investigate the effects
      of CNS glial cells on SC, we examined the effects of serum-free supernatants
      obtained from rat mixed CNS glial cultures on rat neonatal SC cultures.
      Supernatants from 1-, 3-, and 5-day CNS glial cultures induced proliferation of
      SC assayed at 5 days in vitro but did not induce SC differentiation as measured
      by induction of surface expression of galactolipids (GalL). High concentrations
      of cAMP simulate many of the effects of axolemma on SC; CNS glial cell
      supernatants did not inhibit cAMP induction of SC differentiation. CNS glial cell
      supernatants had no apparent effect on SC viability at 48 hr as measured by
      trypan blue exclusion. We have previously demonstrated that incubation of SC with
      transforming growth factor-beta1 (TGF-beta1) + tumor necrosis factor-alpha (TNF
      alpha) induces SC death via apoptosis. We now show that CNS glial supernatants
      inhibits TGF-beta1/TNF-alpha-induced SC death. Our data show that soluble
      products of CNS glial cells do not induce or inhibit SC differentiation or
      increase cell death but have the potential to increase proliferation of SC and
      their resistance to cytokine-mediated death, and thus may affect the outcome of
      SC transplantation into the CNS.

PMID- 16583379
TI  - Triceps brachii muscle demonstrating a fourth head.
AB  - Variations of the triceps brachii muscle are apparently rare. We report an
      additional attachment site of the medial head of the triceps brachii found on the
      left side of a male cadaver. This head originated from the posterior aspect of
      the surgical neck of the humerus. Clinicians diagnosing or treating patients with
      weakness or pain of the posterior arm should consider anomalous muscles in this
      region that may result in neurovascular compression.

PMID- 16583380
TI  - Femoral nerve entrapment: a new insight.
AB  - Compression of the femoral nerve in the iliac fossa has been reported as a
      consequence of several pathologies, but never as a result of muscular
      compression. Aberrant slips of iliacus, however, have occasionally been reported
      to cover or split the femoral nerve. This study aimed to assess such variations
      as potential factors in femoral nerve compression. A large and homogeneous sample
      of 121 embalmed cadavers (242 specimens) was studied. Statistical comparisons
      were made using the chi-squared test. Muscular slips from iliacus and psoas,
      piercing or covering the femoral nerve, were found in 19 specimens (7.9%). No
      significant differences by sex or side were found. The more frequent variation
      was piercing of the femoral nerve by a muscular slip (17 specimens, 7.0%). The
      nerve then entered the thigh as one or more branches. The less frequent variation
      found was a muscular slip or sheet covering the femoral nerve as it lay on
      iliacus (2 specimens, 0.8%). Each disposition may be a potential risk for nerve
      entrapment.

PMID- 16583381
TI  - Expectations of recovery from revision knee replacement.
AB  - OBJECTIVE: To evaluate outcome expectations of patients undergoing revision total
      knee replacement (TKR) and to examine personal factors, patient functioning,
      previous experiences with knee replacement surgery, concerns about surgery, and
      general health as predictors of expectations. METHODS: Revision TKR patients (n =
      184, 54% women; mean age 69 years) completed a questionnaire up to 2 weeks before
      surgery. This included demographics, experience with previous knee surgery,
      concerns about surgery, the Life Orientation Test (LOT), the Arthritis
      Helplessness Scale, the Western Ontario and McMaster Universities Osteoarthritis
      Index, and a rating of overall health. Outcome expectations were evaluated as 5
      questions assessing global benefit; relief of pain; ease of disability;
      expectations of having complications; and whether the person expected to be fully
      recovered from surgery in <6 months, 6-12 months, >12 months, or did not expect
      to recover. Predictors of each of the 5 outcome expectations were evaluated using
      univariable and multivariable regression analyses. RESULTS: Expectations are a
      multidimensional construct (Cronbach's alpha = 0.63). Expectation of global
      benefit of surgery was high, but was lower for benefits related to ease of pain
      and improved function. Concerns about surgery were a consistent predictor of all
      expectation outcomes in multivariable modeling. When concerns about surgery and
      general health were entered into the model as an interaction with expectation of
      recovery time as the outcome, past experience (P = 0.05), pain (P = 0.03), LOT (P
      = 0.03), and interaction between concerns about surgery and general health were
      significant predictors. CONCLUSION: Clinicians need to understand and help
      patients shape appropriate expectations for recovery from revision TKR.

PMID- 16583382
TI  - Inhibition of T cell costimulation: an emerging therapeutic strategy for
      autoimmune rheumatic diseases.

PMID- 16583383
TI  - Medial and lateral pectoral nerves: course and branches.
AB  - During modified radical mastectomy or cosmetic surgery, denervation of the lower
      part of the pectoralis major frequently occurs and may reduce muscle spasm, with
      consequent better reconstruction of the breast. The aim of this study was to
      determine the relationship between the pectoral nerves and the pectoral muscles.
      Eight unembalmed female cadavers were dissected and vascular and radiologic
      studies performed. The lateral pectoral nerves showed a constant course, parallel
      to the thoraco-acromial vessels. They coursed for 55 +/- 7 mm inferomedially on
      the deep surface of pectoralis major, under its fascia. The medial pectoral
      nerves showed two main patterns of branching, which correlated with the extent of
      the costal attachments of the pectoralis minor muscles. In pattern A (56%),
      associated with costal attachments narrower than 6.0 cm, the nerve pierced the
      deep aspect of the pectoralis minor as a single trunk, ramified in the muscle,
      and gave some branches that appeared on the superficial aspect to enter the
      pectoralis major. In pattern B (44%), associated with costal attachments wider
      than 6.6 cm, the nerve divided before entering pectoralis minor and its branches
      passed through the muscle or round its lower border to reach pectoralis major.
      The most medial branch of the medial pectoral nerve directed to the pectoralis
      major muscle emerged from pectoralis minor at the third intercostal space in the
      midclavicular line, a mean of 10.3 cm lateral to the margin of the sternum.
      Knowledge of the relationship between the extent of the costal attachment of
      pectoralis minor and the two patterns of branching of the medial pectoral nerve
      may be useful when performing elective denervation of the major pectoralis
      muscle.

PMID- 16583384
TI  - Catastrophizing and pain in arthritis, fibromyalgia, and other rheumatic
      diseases.
AB  - OBJECTIVE: Pain is among the most frequently reported, bothersome, and disabling
      symptoms described by patients with osteoarthritis, rheumatoid arthritis,
      fibromyalgia, and other musculoskeletal conditions. This review describes a
      growing body of literature relating catastrophizing, a set of cognitive and
      emotional processes encompassing magnification of pain-related stimuli, feelings
      of helplessness, and a generally pessimistic orientation, to the experience of
      pain and pain-related sequelae across several rheumatic diseases. METHODS: We
      reviewed published articles in which pain-related catastrophizing was assessed in
      the context of one or more rheumatic conditions. Because much of the available
      information on catastrophizing is derived from the more general chronic pain
      literature, seminal studies in other disease states were also considered.
      RESULTS: Catastrophizing is positively related, in both cross-sectional and
      prospective studies across different musculoskeletal conditions, to the reported
      severity of pain, affective distress, muscle and joint tenderness, pain-related
      disability, poor outcomes of pain treatment, and, potentially, to inflammatory
      disease activity. Moreover, these associations generally persist after
      controlling for symptoms of depression. There appear to be multiple mechanisms by
      which catastrophizing exerts its harmful effects, from maladaptive influences on
      the social environment to direct amplification of the central nervous system's
      processing of pain. CONCLUSION: Catastrophizing is a critically important
      variable in understanding the experience of pain in rheumatologic disorders as
      well as other chronic pain conditions. Pain-related catastrophizing may be an
      important target for both psychosocial and pharmacologic treatment of pain.

PMID- 16583385
TI  - Tumor necrosis factor inhibitor therapy and risk of serious postoperative
      orthopedic infection in rheumatoid arthritis.

PMID- 16583386
TI  - Cost-effectiveness of nonsteroidal antiinflammatory drug strategies: comment on
      the article by Spiegel et al.

PMID- 16583387
TI  - Etanercept-induced granulomas: comment on the article by Phillips and Weinblatt.

PMID- 16583390
TI  - Aging, arthritis, and disability.

PMID- 16583391
TI  - A rheumatologist's perspective on musculoskeletal ultrasound in rheumatology:
      comment on the editorial by Roemer et al.

PMID- 16583392
TI  - Level of agreement between children, parents, and physicians in rating pain
      intensity in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate the level of agreement between patients, mothers,
      fathers, and physicians in rating pain intensity in juvenile idiopathic arthritis
      (JIA), and to identify factors explaining discrepancies between raters. METHODS:
      Ninety-four children with JIA and their mothers and fathers were asked to rate
      independently the intensity of present pain and pain in the previous week on a
      visual analog scale. The physicians rated pain intensity after physical
      examination. Agreement between raters was determined using intraclass correlation
      coefficient and Bland and Altman method. Correlations of explanatory variables
      with discordance in rating pain intensity were determined by univariate and
      multivariate analyses. Explanatory variables included sex, age, JIA category,
      disease duration, results of study ratings, joint inflammation measures, and
      erythrocyte sedimentation rate. RESULTS: Agreement in rating present pain was
      moderate between children and mothers, but was poor between children and fathers
      and children and physicians. The agreement in rating pain in the previous week
      was moderate between children and mothers and children and fathers. Mother-father
      agreement was good. Parents and physicians agreed at a moderate level. In
      multiple regression analyses, only intensity of present pain was significantly
      associated with discordance within child-mother, child-father, and child
      physician dyads. CONCLUSION: Children's ratings of pain were only in moderate
      agreement with those of their parents and were in poor agreement with those of
      the physicians, whereas the father and mothers agreed at a good level. The
      intensity of pain was the strongest determinant of discordance between children
      and other raters.

PMID- 16583393
TI  - Cost of treatment of childhood-onset systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the direct cost of care of children with childhood-onset
      systemic lupus erythematosus (cSLE), and to determine the direct cost per quality
      adjusted life year (QALY) with cSLE. METHODS: Administrative databases from 2
      large tertiary pediatric rheumatology centers in the United States were reviewed
      for all patients with cSLE (n = 119) diagnosed and regularly treated in these
      centers between January 2001 and April 2004. Health-related quality of life
      estimates for patients with cSLE (n = 297) reported in the literature were used
      to calculate QALYs based on global health ratings of the Child Health
      Questionnaire (range 0-100). RESULTS: Information on 3,184 patient-months of
      followup was included in the analysis. During a mean +/- SD followup of 27 +/-
      11.8 months, the direct cost of care for the cohort amounted to $3,965,048,
      excluding outpatient medications. Irrespective of patient sex, the mean +/- SD
      cost of cSLE per month was $1,245 +/- $2,352, or approximately $14,944 per year.
      Inpatient and day hospital care accounted for 28% of the cost, laboratory testing
      accounted for 21%, inpatient/day-patient medication costs accounted for 13%, and
      dialysis accounted for 11%. Visits to the rheumatology clinic only contributed 9%
      to the direct cost of care. When including an estimated outpatient medication
      cost of $1,190, the direct cost of cSLE per QALY was $30,908. CONCLUSION:
      Children diagnosed with cSLE were found to have a considerable direct cost of
      care. The treatment of cSLE appears to be far more costly than that of adult SLE
      and juvenile idiopathic arthritis reported in the literature.

PMID- 16583394
TI  - Radiologic perspective on musculoskeletal ultrasound: comment on the editorial by
      Roemer et al.

PMID- 16583395
TI  - Why should rheumatologists perform ultrasound? Comment on the editorial by Roemer
      et al.

PMID- 16583398
TI  - Growing up and moving on in rheumatology: parents as proxies of adolescents with
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: To examine agreement about physical health, functional ability, and
      health-related quality of life (HRQOL) between adolescents with juvenile
      idiopathic arthritis (JIA) and their parents. METHODS: The study group comprised
      303 adolescent-parent dyads who completed individual questionnaires, including
      the Childhood Health Assessment Questionnaire with visual analog scales for pain
      and general well-being, and the Juvenile Arthritis Quality of Life Questionnaire.
      Agreement was determined using the Bland and Altman method. RESULTS:
      Approximately half of the adolescent-parent dyads showed clinically acceptable
      agreement for pain, general well-being, functional disability, and HRQOL. Where
      discrepancies occurred, there were similar numbers of parental overestimation and
      underestimation, with the exception that parents rated functional ability worse
      than did adolescents. Parents were also consistent with respect to overestimation
      or underestimation, irrespective of the health domain in question. Agreement was
      associated with better disease-related outcome variables, but was not
      significantly influenced by demographic factors. Agreement between adolescents
      and parents was dependent on the level of disease outcome and the health domain
      under scrutiny, and was less for moderate disease outcomes (as compared with mild
      or severe) and less visible phenomena (e.g., pain, global well-being).
      CONCLUSION: There is a wide variation in agreement between adolescents with JIA
      and their parents that is dependent on which health-related variable is under
      scrutiny. Proxy report is likely to be valid for adolescents with JIA at either
      the mild or severe end of the spectrum and/or for the visible manifestations of
      the disease. Consideration of both adolescent and parent-proxy reports is
      therefore important in future research.

PMID- 16583399
TI  - Health-related quality of life in adolescents with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To describe the health-related quality of life (HRQOL) of adolescents
      with juvenile idiopathic arthritis (JIA), and to examine the usefulness of the
      Juvenile Arthritis Quality of Life Questionnaire (JAQQ) in a UK context. It was
      hypothesized that HRQOL would decrease with worsening disease and disability.
      METHODS: Patients with JIA ages 11, 14, and 17 years were recruited from 10 major
      rheumatology centers. HRQOL was measured using the JAQQ. Other data were core
      outcome variables including the Childhood Health Assessment Questionnaire,
      demographic characteristics, arthritis-related knowledge, and satisfaction with
      health care. RESULTS: Questionnaires were completed by 308 adolescents. One-fifth
      had persistent oligoarthritis. Median disease duration was 5.7 years (range <1-16
      years). The JAQQ was shown to have good psychometric properties when used in the
      UK, but was not without limitations. HRQOL of adolescents with JIA was less than
      optimal, particularly in the domains of gross motor and systemic functioning.
      Items most frequently rated as adolescents' biggest psychological problems were
      "felt frustrated" and "felt depressed," rated by 30.2% and 23.4%, respectively.
      These were particularly problematic for the 17-year-olds, with 39% reporting
      frustration as one of their biggest problems and 63.6% reporting depression.
      Variation in the adolescent JAQQ scores was explained by functional disability,
      pain, and disease activity. CONCLUSION: JIA can have a significant adverse effect
      on the HRQOL of adolescents. The JAQQ is a useful tool to assess the HRQOL of UK
      adolescents with JIA, but there is need for improved measures that incorporate
      developmentally appropriate issues.

PMID- 16583400
TI  - Secondary progressive in contrast to relapsing-remitting multiple sclerosis
      patients show a normal CD4+CD25+ regulatory T-cell function and FOXP3 expression.
AB  - Accumulating evidence indicates an immunosuppressive role for CD4(+)CD25(+)
      regulatory T cells (Tregs) in autoimmune diseases. Although an impaired Treg
      function in patients with relapsing-remitting multiple sclerosis (RR-MS) has been
      reported recently, no information is available so far about Treg function in the
      progressive stage of the disease. In the present study, the phenotypic and
      functional characteristics of CD4(+)CD25(+) T cells isolated from the peripheral
      blood of patients with RR-MS and secondary progressive multiple sclerosis (SP-MS)
      were investigated. No significant quantitative or phenotypic abnormalities in
      CD4(+)CD25(+) T cells from RR- and SP-MS patients were detected. However, whereas
      a reduced suppressor function of CD4(+)CD25(+) T cells toward proliferation and
      interferon-gamma production of CD4(+)CD25(-) responder T cells was found in RR-MS
      patients, SP-MS patients showed a normal Treg function. The suppressive capacity
      of MS-derived CD4(+)CD25(+) T cells was correlated with disease duration but not
      with age, indicating that Treg function is more affected in the early phase of
      the disease process. Consistently with the suppressive capacity, CD4(+)CD25(+) T
      cells from SP-MS patients showed normal levels of FOXP3 mRNA in contrast to RR-MS
      patients that had a reduced FOXP3 expression. These data are the first to
      demonstrate differences in function and FOXP3 expression of CD4(+)CD25(+) T cells
      from patients with RR- and SP-MS.

PMID- 16583401
TI  - Phosphorylation of the neural cell adhesion molecule on serine or threonine
      residues is induced by adhesion or nerve growth factor.
AB  - The neural cell adhesion molecule (NCAM) is a member of the immunoglobulin
      superfamily and plays a crucial role during development and regeneration. It is
      expressed in three major isoforms; two of them with intracellular domains of
      different length and one without any intracellular domain. NCAM is known to be
      phosphorylated and contains up to 49 serine or threonine residues, which could be
      phosphorylated. However, the impact of NCAM phosphorylation is still unclear.
      Here we describe NCAM being phosphorylated during neuronal differentiation of
      PC12 cells. We provide evidence that protein kinase C is involved in the
      phosphorylation of NCAM. In agreement with our earlier observation that the
      protein phosphatase 1 is associated with NCAM, we additionally found that NCAM is
      a substrate for the protein phosphatase 1 but not for the protein phosphatase 2A.

PMID- 16583402
TI  - Functional expression of A glutamine transporter responsive to down-regulation by
      lipopolysaccharide through reduced promoter activity in cultured rat neocortical
      astrocytes.
AB  - The prevailing view is that the glutamine (Gln) transporter
      (GlnT/ATA1/SAT1/SNAT1) is a member of the system A transporter superfamily with
      the ability to fuel the glutamate/Gln cycle at nerve terminals in glutamatergic
      neurons. Semiquantitative reverse transcription-polymerase chain reaction
      revealed similarly high expression of mRNA for GlnT by rat brain neocortical
      astrocytes as well as neurons, with progressively lower expression by cerebellar
      astrocytes, hippocampal astrocytes, and whole-brain microglia in culture.
      [(3)H]Gln was accumulated in a temperature-dependent manner with a saturable
      profile in both cultured neocortical neurons and astrocytes, whereas biochemical
      and pharmacological analyses on [(3)H]Gln accumulation revealed the expression of
      both system A and system L transporters by cultured neocortical neurons and
      astrocytes. Exposure to lipopolysaccharide (LPS) for 24 hr resulted in a
      significant decrease in both GlnT mRNA expression and [(3)H]Gln accumulation,
      with a concomitant drastic increase in nitrite formation in cultured neocortical
      astrocytes. Moreover, LPS significantly inhibited the promoter activity of GlnT
      in the astrocytic cell line C6 glioma cells as well as primary rat neocortical
      astrocytes in culture. These results suggest that activation by LPS would lead to
      down-regulation of the expression of GlnT responsible for the incorporation of
      extracellular Gln into intracellular spaces across plasma membranes through the
      inhibition of its promoter activity in cultured rat neocortical astrocytes.

PMID- 16583404
TI  - Care of the adult with juvenile rheumatoid arthritis.

PMID- 16583403
TI  - Genetically modified bone morphogenetic protein signalling alters traumatic brain
      injury-induced gene expression responses in the adult mouse.
AB  - Three genetic mouse models were examined to define effects of bone morphogenetic
      protein (BMP) signalling on gene expression in normal and injured adult brain.
      CaMKII-Cre eliminated the BMP receptor Acvr1 (Alk2) and the common TGFbeta
      superfamily signal mediator Smad4 or activated a constitutively active Acvr1 in
      postnatal forebrain neurons. All mutants followed mendelian ratios, with no overt
      phenotypic changes. In situ hybridization demonstrated normal patterns of the
      dendritic marker MAP2 (Mtap2) throughout cortex despite neuron-specific losses of
      Acvr1 or Smad4. However, strong up-regulation of Mtap2 transcript in these mice
      was found by quantitative RT-PCR (qRT-PCR), indicating that Mtap2 is normally
      suppressed by BMP. Traumatic brain injury (TBI) resulted in increases of histone
      associated DNA fragments in both control and Smad4-deficient cortex. Several cell
      type-specific transcripts known to be involved in injury-related responses were
      measured by qRT-PCR. Gfap mRNA was strongly up-regulated in controls as well as
      in the loss-of-BMP-signalling mutants. Notably, activated Acvr1 signalling gave
      significantly lower TBI-induced up-regulations of Gfap and Phox2a mRNA levels,
      indicating reductions in astroglial and neuronal reactions to injury. Strong
      impairment in injury-induced Timp1 transcript up-regulation was also seen in
      these mice. In contrast, osteopontin (Spp1) transcript levels in activated
      microglia were not reduced by Acvr1 signalling. Altogether, the data suggest that
      BMP signalling is dispensable in adult cortical neurons but that augmented BMP
      signalling affects molecular changes associated with neuronal lesions.

PMID- 16583405
TI  - Childbearing decisions and family size among women with rheumatoid arthritis.
AB  - OBJECTIVE: To estimate childbearing trends relative to age and stage of family
      development and to report on childbearing decisions among women with rheumatoid
      arthritis (RA). METHODS: Information about childbearing history and decisions was
      collected through structured telephone interviews with an existing cohort of
      married women with RA (n = 411), and was examined according to women's age at RA
      diagnosis and when RA was diagnosed relative to when children were born. RESULTS:
      Almost all women (91.2%) reported at least 1 pregnancy; the majority (85.4%)
      reported at least 1 live birth. The odds of any pregnancy or a live birth were
      not significantly different according to age at diagnosis; however, women
      diagnosed at age < or =18 had fewer pregnancies and fewer children. Similarly,
      women diagnosed with RA prior to the birth of their first child had the fewest
      pregnancies and children. Few women (8%) reported being advised to limit family
      size, although approximately 20% reported that RA had affected their childbearing
      decisions. Being advised to limit family size was associated with fewer
      pregnancies and fewer children (P < 0.0001). Consideration of RA in childbearing
      decisions was more common among women diagnosed with RA at an early age. Women
      who reported that RA affected childbearing decisions were not less likely to have
      any pregnancy or any children, but had significantly fewer pregnancies and
      children. CONCLUSION: Lower birth rates among women with RA may at least in part
      reflect choices by women to limit family sizes. Future research into the link
      between RA and fertility should take women's childbearing choices into account.

PMID- 16583406
TI  - Weight gain associated with the alpha2a-adrenergic receptor -1,291 C/G
      polymorphism and olanzapine treatment.
AB  - Weight gain can be an adverse effect of antipsychotics and is an important factor
      for long-term health and treatment compliance. Many reports have shown that the
      alpha(2)-adrenergic receptor may be related to eating behaviors or lipolytic
      activities, both associated with body weight change. We hypothesized that there
      might be a relationship between the alpha(2a)-adrenergic receptor -1,291 C/G
      polymorphism and olanzapine-induced weight gain. A group of 62 Korean
      schizophrenic patients participated in a study; weight and height measurements
      were obtained prior to starting olanzapine and measured again after long-term
      treatment. Genotyping for the -1291 C/G polymorphism was performed on all
      participants. Body weight changes from baseline to endpoint were significantly
      associated with genotypes (P = 0.028). The frequency of the G allele was
      significantly higher in subjects who had severe weight gain (defined as a more
      than 10% weight gain from baseline) compared to subjects who did not have extreme
      weight gain (less than 10% weight gain from baseline) (X(2) = 6.120, P = 0.013;
      OR = 2.58, 95% CI = 1.21-5.51). Therefore, the findings from this study support a
      relationship between the -1291 C/G polymorphism of the alpha(2a)-adrenergic
      receptor and weight gain in Korean schizophrenic patients receiving olanzapine
      treatment.

PMID- 16583407
TI  - Preliminary evidence for an association between a dopamine D3 receptor gene
      variant and obsessive-compulsive personality disorder in patients with major
      depression.
AB  - We have previously reported that the Ser9Gly dopamine D3 receptor (DRD3)
      polymorphism was associated with increased rates of obsessive-compulsive
      personality disorder (OCPD) symptomology. We tested the replicability of this
      association within a further two independent groups of individuals with a history
      of depression, from a clinical sample (n = 149) and a family study (n = 213). The
      data from the replication samples and the original sample, within which the
      association was found, were compiled within a meta-analysis. Although the
      independent samples did not replicate the original finding, the meta-analysis
      elucidated significant evidence supporting the association. An individual with
      Gly/Gly genotype is 2.4 (P = 0.017) times more likely to be diagnosed with OCPD.
      Male gender was also found to be a significant predictor of OCPD diagnosis (OR =
      2.82, P = 0.001). An exploration of an association of DRD3 with Axis I anxiety
      disorder diagnoses and Temperament and Character Inventory (TCI) traits, in
      particular persistence, revealed no support for an association. We conclude that
      DRD3 may contribute to the development of OCPD.

PMID- 16583408
TI  - Association between the DRD2 A1 allele and response to methadone and
      buprenorphine maintenance treatments.
AB  - The TaqI A polymorphism (A(1)) of the dopamine D(2) receptor gene (DRD2),
      although not a specific predictor of opioid dependence, has been strongly
      associated with high levels of prior heroin use and poor treatment outcomes among
      methadone maintenance patients. The aims of this study were to confirm these
      findings via a retrospective analysis of A(1) allele frequency in methadone (n =
      46) and buprenorphine (n = 25) patients, and non-opioid-dependent controls (n =
      95). Subjects were genotyped at the DRD2 TaqI A locus using PCR amplification
      followed by TaqI restriction enzyme digestion and gel electrophoresis. For
      methadone and buprenorphine subjects, heroin use (prior to treatment), treatment
      outcomes, and withdrawal occurrence were determined from comprehensive case
      notes. No significant differences in A(1) allele frequency (%) were observed
      between: methadone (19.6%), buprenorphine (18.0%), and control (17.9%) groups (P
      > 0.7); successful and poor treatment outcome groups, methadone: 20.0% and 19.2%,
      respectively (P = 1.0); buprenorphine: 18.4% and 20.0%, respectively (P = 1.0).
      Also, there were no significant relationships between TaqI A genotype and prior
      heroin use (P = 0.47). However, among the successful methadone subjects,
      significantly fewer A(1) allele carriers experienced withdrawal than non-A(1)
      carriers (P = 0.04). In conclusion, the DRD2 genotype effects did not affect
      opioid maintenance treatment outcomes. This suggests the need for a further
      prospective investigation into the role of the DRD2 A(1) allele in heroin use and
      response to maintenance pharmacotherapies for opioid dependence.

PMID- 16583409
TI  - Illness intrusion and psychological adjustment to rheumatic diseases: a social
      identity framework.
AB  - OBJECTIVE: To examine the extent to which arthritis intruded upon 4 social roles
      (spouse, homemaker, parent, worker). In accordance with propositions set forth by
      social identity theory and the identity-relevant stress hypothesis, we
      hypothesized that 1) illness intrusion would predict psychological well-being and
      2) role importance would moderate the relationship between illness intrusion and
      psychological adjustment, such that intrusion into highly valued roles would be
      the most psychologically distressing. METHODS: Participants were recruited from
      the practices of rheumatologists affiliated with a major urban hospital. A total
      of 113 individuals (73% women) with diagnosed rheumatic disease completed a
      mailed questionnaire. RESULTS: For all 4 roles, illness intrusion was related to
      decreased psychological well-being. In the worker and parent roles, the effects
      of illness intrusion on adjustment were moderated by whether respondents valued
      these particular roles. For example, psychological well-being was lowest among
      those individuals whose illness intruded greatly upon work and who highly valued
      their worker role identity. CONCLUSION: The findings highlight the advantages of
      assessing both domain-specific illness intrusion and role importance in
      predicting psychological well-being among persons with rheumatic diseases.
      Importantly, results also demonstrate the utility of applying a social identity
      framework in understanding adjustment processes among persons with chronic
      illness.

PMID- 16583410
TI  - Haplotype analysis of single nucleotide polymorphisms in VEGF gene for vascular
      dementia.
AB  - A case-control study was performed to identify single nucleotide variants of
      vascular endothelial growth factor (VEGF) gene associated with vascular dementia.
      Seven SNPs in promoter, 5'-UTR, 3'-UTR, and introns of VEGF gene were identified
      in 24 Koreans. Three of them, -1154G/A, -7C/T, and 13553C/T, were selected based
      on allele frequency and linkage disequilibrium (LD), and genotyped in 207
      vascular dementia patients and 207 control subjects. Significant association with
      vascular dementia was not shown (P > 0.05) in the alleles and genotypes of single
      locus. Subsequent analysis of composing VEGF risk haplotypes associated with
      vascular dementia was performed with maximum likelihood estimates of their
      possible haplotypes employing the expectation-maximization (EM) algorithm. Of
      three-locus haplotypes, only GTC was significantly associated with vascular
      dementia, conferring a risk of 1.87 (P < 0.05). Of two-locus haplotypes, the risk
      was observed with the nested forms of the risk haplotype GTC, that is, GT at the
      loci -1154G/A and -7C/T and TC at the loci -7C/T and 13553C/T (P < 0.05). Our
      findings suggested some interaction among -1154G/A, -7C/T, and 13553C/T variants
      in the determination of risk for vascular dementia.

PMID- 16583411
TI  - Future ethical use of genetic findings on schizophrenia: comments on data
      interpretation, and support for conclusions.

PMID- 16583413
TI  - Reexamining the arthritis-employment interface: perceptions of arthritis-work
      spillover among employed adults.
AB  - OBJECTIVE: To examine employed individuals' perceptions of arthritis-work
      spillover (AWS), the reciprocal influence of arthritis on work and work on
      arthritis, and the demographic, illness, and work context factors associated with
      AWS. METHODS: The study group comprised 492 employed individuals with
      osteoarthritis or inflammatory arthritis. Participants completed an interview
      administered, structured questionnaire assessing AWS, demographic (e.g., age,
      sex), illness (e.g., disease type, pain, activity limitations), and work context
      (e.g., workplace control, hours of work) variables. Principal components
      analysis, reliability analysis, and multiple linear regression were used to
      analyze the data. RESULTS: A single factor solution emerged for AWS. The scale
      had an internal reliability of 0.88. Respondents were more likely to report that
      work interfered with caring for their arthritis than they were to report that
      their disease affected their work performance. Younger respondents, those with
      more fatigue and workplace activity limitations, and those working in trades and
      transportation reported more AWS. Individuals with more control over their work
      schedules reported less AWS. CONCLUSION: The results of this study extend
      research on arthritis by reexamining the interface between arthritis and
      employment. This study introduces a new measure of AWS that enhances the range of
      tools available to researchers and clinicians examining the impact of arthritis
      in individuals' lives.

PMID- 16583414
TI  - Quality of osteoarthritis care for community-dwelling older adults.
AB  - OBJECTIVE: To describe the quality of osteoarthritis care provided to community
      dwelling elderly patients and to characterize arthritis-related function in these
      patients. METHODS: Two medical groups in the western United States participated
      in a practice-redesign intervention targeted at falls and mobility disorders,
      incontinence, and cognitive impairment, but not osteoarthritis. From 339
      individuals reporting a diagnosis of arthritis, we collected information on
      demographics, functional status, and quality of care via patient interviews and
      mailed questionnaires. Eight quality indicators measured osteoarthritis care: 4
      indicators measuring the provision of effective osteoarthritis care
      (osteoarthritis treatment indicators) and 4 measuring the provision of safe
      osteoarthritis care (medication safety indicators). RESULTS: The mean +/- SD
      Short Form 12 physical component summary score was 35 +/- 11 points, indicating a
      physically frail population. The overall indicator pass rate was 57.0% (95%
      confidence interval [95% CI] 53.9-60.2). Pass rates were higher for indicators of
      osteoarthritis treatment (63.5%, 95% CI 59.8-67.2) than for indicators of
      medication safety (43.8%, 95% CI 38.2-49.4). Patients with hip or knee pain had
      mean +/- SD Western Ontario and McMaster Universities Osteoarthritis Index pain,
      stiffness, and function scores of 6.0 +/- 4.0, 3.1 +/- 1.7, and 25 +/- 12 points,
      respectively. CONCLUSION: Quality of osteoarthritis care for older adults is
      suboptimal, particularly with regard to medication safety. Given the high
      prevalence of osteoarthritis in older age groups, the population impact of any
      improvement in quality would be substantial. Quality improvement efforts for
      osteoarthritis should target appropriate use of and counseling regarding
      medications, as well as underuse of efficacious therapy for osteoarthritis.

PMID- 16583416
TI  - Transitions to mobility difficulty associated with lower extremity osteoarthritis
      in high functioning older women: longitudinal data from the Women's Health and
      Aging Study II.
AB  - OBJECTIVE: To assess the impact of lower extremity osteoarthritis (OA) on
      transitions to mobility difficulty, and to assess the influence of pain, excess
      weight, and quadriceps strength on these transitions. METHODS: We analyzed
      longitudinal data acquired from 199 participants in the Women's Health and Aging
      Study II (ages 70-79 years) who initially reported no lower extremity limitation
      (e.g., difficulty walking one-quarter mile) or difficulty in activities of daily
      living (ADL; e.g., transferring). Prevalent lower extremity OA was determined
      from validated algorithms encompassing multiple data sources. Markov transition
      models were created to analyze the first transition from no difficulty at
      baseline to lower extremity limitations, ADL difficulty, or both 18, 36, and 72
      months later. RESULTS: Compared with women without OA (n = 140), a higher
      proportion of women with lower extremity OA (n = 59) initially reported pain on
      most days and more severe pain while walking (P < 0.05). Women with OA were also
      heavier, with a higher proportion being obese or overweight (P < 0.001). Lower
      extremity OA, higher body mass index, and lower knee extensor strength
      independently increased the risk of transition to combined lower extremity and
      ADL difficulty first over 72 months. CONCLUSION: Lower extremity OA increased the
      likelihood of developing difficulty in both lower extremity tasks and ADL over 72
      months in a cohort of initially high functioning older women. Two modifiable
      factors, higher relative weight and lower knee extensor strength, substantially
      impacted these transitions, and therefore warrant increased attention in the
      management of lower extremity OA.

PMID- 16583415
TI  - Population impact of arthritis on disability in older adults.
AB  - OBJECTIVE: Disability threatens the independence of older adults and has large
      economic and societal costs. This article examines the population impact of
      arthritis on disability incidence among older Americans. METHODS: The present
      study used longitudinal data (1998-2000) from the Health and Retirement Study, a
      national probability sample of elderly Americans. Disability was defined by the
      inability to perform basic activities of daily living (ADL). A total of 7,758
      participants ages > or =65 years with no ADL disability at baseline were included
      in the analyses. Multiple logistic regression was used to measure the impact of
      baseline arthritis (self reported) on incidence of subsequent ADL disability
      after controlling for baseline differences in demographics, health factors,
      health behaviors, and medical access. RESULTS: Older adults who had baseline
      arthritis had a substantially higher incidence of ADL disability compared with
      those without arthritis (9.3% versus 4.5%). The strong relationship of arthritis
      and ADL disability was partially explained by demographic, health, behavioral,
      and medical access factors. However, even after adjusting for all other risk
      factors, arthritis remained as an independent and significant predictor for
      developing ADL disability (adjusted odds ratio 1.5, 95% confidence interval 1.2
      1.8). Almost 1 in every 4 new cases of ADL disability was due to arthritis
      (adjusted population attributable fraction: 23.7%). CONCLUSION: The high
      frequency of incident ADL disability attributable to arthritis points to the
      importance of intervention programs that address the entire spectrum of health
      and functional problems in persons with arthritis to prevent disability.

PMID- 16583417
TI  - Correlates of knee pain in older adults: Tasmanian Older Adult Cohort Study.
AB  - OBJECTIVE: To describe the association between chondral defects, bone marrow
      lesions, knee and hip radiographic osteoarthritis (OA), and knee pain. METHODS:
      Knee pain was assessed by the Western Ontario and McMaster Universities
      Osteoarthritis Index. T1- and T2-weighted fat saturation magnetic resonance
      imaging was performed on the right knee to assess chondral defects and
      subchondral bone marrow lesions. Radiography was performed on the right knee and
      hip and scored for radiographic OA. Body mass index (BMI) and knee extension
      strength were measured. RESULTS: A total of 500 randomly selected men and women
      participated. The prevalence of knee pain was 48%. In multivariable analysis,
      prevalent knee pain was significantly associated with medial tibial chondral
      defects (odds ratio [OR] 2.32, 95% confidence interval [95% CI] 1.02-5.28 for
      grade 3 versus grade 2 or less; OR 4.93, 95% CI 1.07-22.7 for grade 4 versus
      grade 2 or less), bone marrow lesions (OR 1.44, 95% CI 1.04-2.00 per
      compartment), and hip joint space narrowing (OR 1.36, 95% CI 1.07-1.73 per unit),
      as well as greater BMI and lower knee extension strength. It was not
      significantly associated with radiographic knee OA. These variables were also
      associated with more severe knee pain. In addition, there was a dose response
      association between knee pain and number of sites having grade 3 or 4 chondral
      defects (OR 1.39, 95% CI 1.12-1.73 per site), with all subjects having knee pain
      if all compartments of the knee had these defects. CONCLUSION: Knee pain in older
      adults is independently associated with both full and non-full-thickness medial
      tibial chondral defects, bone marrow lesions, greater BMI, and lower knee
      extension strength, but is not associated with radiographic knee OA. The
      association between radiographic hip OA and knee pain indicates that referred
      pain from the hip needs to be considered in unexplained knee pain.

PMID- 16583418
TI  - How "bad" does the pain have to be? A qualitative study examining adherence to
      pain medication in older adults with osteoarthritis.
AB  - OBJECTIVE: To explore the experience of adherence to pain medication in older
      adults with osteoarthritis (OA). METHODS: Individuals were recruited from an
      existing cohort (n = 1,300) of persons with disabling hip and knee OA. Twenty
      seven individuals who reported previous physician visits for their arthritis,
      spoke English, were Toronto residents, and were receptive to in-depth interviews
      were approached by the cohort telephone interviewer to discuss their experiences
      with prescribed painkillers for OA. Semistructured face-to-face interviews were
      conducted by a qualitative researcher in participants' homes. RESULTS: Nineteen
      adults (10 women, 9 men) ages 67-92 years were interviewed for 1-3 hours.
      Participants varied in their socioeconomic status and education levels. Most had
      comorbidities, such as heart disease and diabetes, for which they were also being
      treated. Findings indicated that adherence to pain medication differed from that
      of other prescribed medications. Participants were reluctant to take painkillers,
      and when they did, they generally took them at a lower dose or frequency than
      prescribed. This behavior did not reflect their recommendations for others, who
      they expected to be treated appropriately for pain and to adhere to pain
      medication. Perceptions and attitudes to pain played an integral role in
      participants' adherence to painkillers. Despite obvious physical limitations,
      participants minimized their pain and claimed to have a high pain tolerance.
      CONCLUSION: These findings suggest that reevaluation of the prescription of pain
      medication for OA is warranted and that the effectiveness of pain management in
      OA needs to account for adherence behavior in older adults.

PMID- 16583419
TI  - Atypical anastomosis of laryngeal nerves.
AB  - The larynx and its associated structures derive their chief source of innervation
      from the superior and recurrent laryngeal nerves. Surgery of the larynx requires
      a sound knowledge of the normal anatomy as well as variations that may be
      encountered in this region. We report the presence of rare communications between
      the right external and internal laryngeal nerves as well as between the right
      external and inferior laryngeal nerves via a thyroid foramen. In addition, we
      report on bilateral innervation of the respective ipsilateral aryepiglottic,
      transverse, and oblique arytenoid muscles by the internal laryngeal nerve, which
      is contrary to the classical descriptions of this nerve. The anatomic features
      are described and clinical implications are highlighted.

PMID- 16583420
TI  - Mondino de' Liuzzi and his Anothomia: a milestone in the development of modern
      anatomy.
AB  - Mondino's Anothomia was written in Bologna around 1316. This book is the
      intellectual legacy of one of the fathers of human anatomy, and probably
      represents a collection of lessons given by the author at the Studium in Bologna.
      Mondino's Anothomia witnesses a profound renewal of the mode of understanding and
      teaching human anatomy through direct observation of dissected corpses. This book
      enjoyed an extraordinarily large dissemination in the whole of Europe, thanks to
      many extant manuscripts and printed editions. In this article, we present some
      selected passages from this remarkable book to let today's anatomists know how
      great was the descriptive skill of this medieval scientist, a pioneer in the
      anatomical discipline.

PMID- 16583421
TI  - Different patterns of illness-related interaction in couples coping with
      rheumatoid arthritis.
AB  - OBJECTIVE: To learn more about the effect of rheumatoid arthritis (RA) on
      couples' relationships and how couples manage the illness within their dyad.
      METHODS: Eight women with RA (ages 31-60 years) and their partners, and 4 men
      with RA (ages 43-75 years) and their partners were recruited from the
      rheumatology case load of a hospital in the UK. Interpretative phenomenologic
      analysis was used for data collection and analysis. During semistructured
      interviews, couples were asked about the effect of RA on their lives and
      relationship. RESULTS: This study found clear differences in the way couples
      managed the illness of one partner and in the nature of their illness-related
      interactions. Based on these differences, the couples were allocated to 1 of 3
      groups: the shared illness management group (SIM), the ill partner in charge
      group (IPIC), or the conflict over management group (COM). In the SIM group, both
      partners attended appointments and shared decisions about illness management. In
      the IPIC group, the ill person claimed and was conceded the right to make
      autonomous decisions about illness management. In the COM group, the well partner
      was dissatisfied with the way the ill person was managing the illness, and
      conflict resulted. CONCLUSION: Heterogeneity exists in the intradyad management
      of RA. Identifying each couple's style of illness management could make medical
      consultations and education programs more responsive to the needs and preferences
      of patients and their partners. Dissatisfaction of either partner with illness
      management and resulting conflict could be addressed, with benefits for both
      partners and possible improvement in disease management.

PMID- 16583422
TI  - Proto-professionalism and the dissecting laboratory.
AB  - This essay argues for medical students' dissection of cadavers because this
      activity offers medical students opportunities to have certain experiences and
      reflect on them in ways facilitating their development of mature medical
      professionalism at the time they enter clinical practice. Issues central to
      professionalism as we envision it are (1) cognitive abilities identified as
      reflective judgment and principled ethical reasoning as they are exercised in
      four practice domains and (2) learning to learn in medical settings. We argue
      further that a key feature of such setting is practitioners' having to deal with
      ill-structured problems, and so we identify their features and relate their
      management to the sophisticated cognitive and learning abilities required of
      medical professionals.

PMID- 16583423
TI  - The surgical anatomy of the ansa pectoralis.
AB  - Detailed anatomical knowledge of the pectoral nerves is of clinical importance in
      surgeries as diverse as limb neurotization, mastectomy, orthopedic procedures and
      operations related to trauma. The brachial plexus of 200 cadavers were examined
      in an attempt to clarify the normal origins, courses and variations of the nerves
      with special emphasis on the ansa pectoralis (AP). In 75% the MPN arose from the
      anterior division of the inferior trunk of the brachial plexus and in 25% it
      arose from the medial cord. In 40% of specimens, the LPN arose from a single
      contributing nerve (anterior division of the superior trunk, 11%; anterior
      division of the middle trunk 18%; lateral cord, 11%). In the remaining 60% of
      specimens, the LPN arose from the fusion of two rootlets derived variably from
      the anterior divisions of the superior and middle trunks and the lateral cord. A
      single AP was found to be present bilaterally in 200 (100%) of the specimens.
      Classification of the AP was based upon its origin from the upper or lower
      rootlet of the LPN, the LPN itself, or from the deep branch of the LPN. AP-1
      (42%) arose from the deep branch of the LPN; AP-2 (28%) arose directly from the
      LPN; AP-3 (25%), arose from the lower rootlets of the LPN and rarely, the AP
      arose from the upper rootlet of the LPN and crossed posterior to the lower
      rootlet to communicate with the MPN (AP-4, 5%). Irrespective of the
      aforementioned types, the AP was found to be present, crossing the second segment
      of the axillary artery in 90% of the specimens. These results could prove useful
      during the preoperative planning of neurotization and other surgical procedures
      involving the axilla.

PMID- 16583424
TI  - Effect of etanercept on fatigue in patients with recent or established rheumatoid
      arthritis.
AB  - OBJECTIVE: To assess the long-term impact of etanercept on fatigue in patients
      with recent-onset (mean duration 11 months) or established (mean duration 12
      years) rheumatoid arthritis (RA). METHODS: Patients participating in either of 2
      multicenter, randomized, double-blind clinical trials were included. In one
      trial, patients with recent-onset RA received either etanercept 25 mg twice
      weekly or methotrexate in a double-blind fashion for 12 months, then open label
      for 12 months. All patients then received open-label etanercept. In the second
      trial, patients with established RA received etanercept 25 mg or placebo twice
      weekly for 6 months in a double-blinded fashion, then open-label etanercept. Up
      to 46 months of followup data were included. Fatigue was measured regularly using
      the Health Assessment Questionnaire vitality domain. RESULTS: Patients with
      recent-onset RA who received etanercept had a significantly faster improvement in
      fatigue than those receiving methotrexate in the first 2 months. Subsequently,
      patients receiving etanercept and methotrexate had 23-29% and 17-24% reductions
      in fatigue scores, respectively. In the group with established RA, patients who
      received etanercept had significantly greater reductions in fatigue than those
      receiving placebo during the blinded period. Patients initially receiving
      etanercept sustained a mean fatigue reduction of 25-36% for the entire followup.
      Patients achieving clinically meaningful improvement in fatigue were more likely
      to meet the American College of Rheumatology improvement criteria. CONCLUSION:
      Etanercept therapy reduces fatigue in patients with recent-onset or established
      RA. Improvement in fatigue was sustained for up to 46 months, and correlated with
      other RA-relevant outcomes.

PMID- 16583426
TI  - Contrahentes digitorum muscle.

PMID- 16583427
TI  - Extent of occupational hand use among persons with rheumatoid arthritis.
AB  - OBJECTIVE: Occupational hand use is increasing due to increased computer use and
      could place persons with rheumatoid arthritis (RA) at risk for work disability.
      Although hand involvement in RA is typical, there is little information about
      occupational hand use in relation to RA. Study objectives were to describe the
      extent of occupational hand use by persons with RA; the types of jobs that
      require extensive hand use; the relationship between occupational hand use and
      joint pain; and the extent of occupational hand use among persons with shorter
      versus longer disease duration. METHODS: Cross-sectional survey data from 2,761
      employed participants with RA from a US national cohort were used. Extent of
      occupational hand use was measured by the hand-use item from a job physical
      demand scale used in prior RA studies. Analyses included descriptive statistics
      and chi-square tests. RESULTS: The mean age was 50.6 years, 78.5% were women,
      91.8% were white, and 68.8% had more than a high school education. Eighty-three
      percent of participants reported extensive occupational hand use. Large portions
      of participants in all types of jobs reported extensive hand use, 92% with
      administrative support jobs and 69% with operator/laborer jobs. Participants with
      extensive occupational hand use were more likely to have hand joint pain than
      those with moderate hand use (66% versus 58%; P = 0.004). Extensive hand use did
      not vary by disease duration (83% and 84% in participants with < or =15 and >15
      years' duration, respectively). CONCLUSION: Extensive occupational hand use was
      ubiquitous among employed persons with RA and was associated with greater hand
      pain.

PMID- 16583428
TI  - What factors account for referral delays for patients with suspected rheumatoid
      arthritis?
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a common, costly, and disabling disease.
      Early referral and treatment reduce long-term joint damage and improve functional
      outcomes. Despite efforts to improve referral, half of patients with RA are not
      referred in a timely manner. Our objective was to explore the factors influencing
      the decision of a primary care physician (PCP) to refer or not refer a patient
      with suspected RA, and to identify modifiable factors influencing timely
      referral. METHODS: Using qualitative methods and in-depth, face-to-face
      interviews, we asked Connecticut PCPs to describe the last patient encounter
      where they suspected RA and the factors influencing referral and nonreferral.
      Participants represented a range of clinical experience, access to
      rheumatologists, and practice settings. Sample size was determined by thematic
      saturation. Transcripts were coded and analyzed using the constant comparative
      method of qualitative data analysis. RESULTS: We interviewed 19 PCPs, 9 of whom
      were women. Our analysis identified clinical characteristics, patient
      preferences, access issues, clinical and administrative leadership, physician
      confidence and expectations, and interpersonal relationships as important domains
      influencing the referral decision. These domains interacted to impact timely
      referral and quality of care. Previously underappreciated factors, such as the
      magnitude of the effect of physician rapport, appeared to be critical in
      determining whether or not patients are promptly referred. CONCLUSION: Issues
      such as physician rapport, as well as clinical and system issues, influence
      referral for suspected RA. To improve referral for RA, clinical guidelines,
      medical education, and quality improvement efforts should address all domains
      influencing the referral decision.

PMID- 16583429
TI  - Trapezius aplasia: indications for a dual developmental origin of the trapezius
      muscle.
AB  - Aplasia of the trapezius muscle is a rarely encountered, mostly asymptomatic
      anomaly. We report a case of isolated unilateral complete trapezius aplasia that
      was noticed during a dissection course. Apart from isolated cases, trapezius
      aplasia may occur in different combinations with other muscle aplasias. We
      suggest that the patterns of concomitant muscle involvement are indicative of a
      combined occipital and cervical somitogenic origin.

PMID- 16583430
TI  - Is there an alternative to the full-leg radiograph for determining knee joint
      alignment in osteoarthritis?
AB  - OBJECTIVE: To assess the concurrent validity of alternative measures of frontal
      plane knee alignment, namely the radiographic anatomic axis and 5 clinical
      measures, in medial compartment knee osteoarthritis (OA) as compared with the
      mechanical axis on radiograph. METHODS: Forty individuals (mean +/- SD age 64.7
      +/- 9.4 years) with symptomatic medial knee OA participated. Knee alignment was
      measured according to the following methods: lower-limb mechanical axis on
      radiograph, lower-limb anatomic axis on radiograph, visual observation, distance
      between medial knee joint lines or medial malleoli using a caliper, distance
      between a plumb line and medial knee joint line or malleolus using a caliper,
      tibial alignment using a gravity inclinometer, and lower-limb alignment using a
      goniometer. Data were analyzed using Pearson's correlation coefficient or
      Spearman's rho correlation coefficient and simple linear regression. RESULTS: The
      anatomic axis best correlated with the mechanical axis (r = 0.88), followed
      closely by the inclinometer method (r = 0.80). Other clinical measures of
      alignment that were significantly associated with the mechanical axis were the
      caliper method, the plumb-line method, and visual observation (r = 0.76, 0.71,
      and -0.52, respectively). However, the goniometer method failed to correlate.
      CONCLUSION: The anatomic axis on radiograph and the inclinometer method appear to
      be valid alternatives to the mechanical axis on full-leg radiograph for
      determining frontal plane knee alignment in medial knee OA. These alternative
      methods of measuring knee alignment may increase the assessment of this parameter
      by clinicians and researchers alike, given that malalignment is an important
      indicator of disease progression and treatment outcome.

PMID- 16583431
TI  - Thalidomide therapy for myelofibrosis with myeloid metaplasia.
AB  - BACKGROUND: Thalidomide is a putative antiangiogenesis agent with activity in
      several hematologic malignancies. METHODS: Forty-four patients who had
      myelofibrosis with myeloid metaplasia received treatment with thalidomide in a
      Phase II clinical trial at a dose of 200 mg daily with escalation by 200 mg
      weekly until the best tolerated dose (maximum, 800 mg) was reached. RESULTS:
      Seventeen of 41 evaluable patients (41%) who received treatment for at least 15
      days had a response. A complete response (without reversal of bone marrow
      fibrosis) was achieved in 4 patients (10%), a partial response was achieved in 4
      patients (10%), and hematologic improvements in anemia, thrombopenia, and/or
      splenomegaly were observed in 9 patients (21%). Improvements in anemia occurred
      in 7 of 35 patients (20%) with hemoglobin levels <10.0 g/dL, and improvements in
      thrombopenia occurred in 5 of 24 patients (21%) with platelet counts <100 x
      10(9)/L. Five of 24 patients (21%) became transfusion-independent. Major or minor
      regression of splenomegaly was noted in 9 of 29 evaluable patients (31%), and
      complete regression was noted in 5 patients. Responders had a lower baseline
      median vascular endothelial growth factor levels (77.9 pg/mL vs. 97.7 pg/mL; P
      <.01) and higher median basis fibroblast growth factor levels (60.8 pg/mL vs.
      37.4 pg/mL; P <.01) compared with nonresponders. Nine patients (22%) had
      deterioration that was attributed to thalidomide (resolved after withdrawal) with
      either progressive cytopenias or excessive proliferation. Two patients developed
      Grade 3 neutropenia with recovery and resumed therapy with dose reductions, and
      both later achieved a complete response. Dose-related toxicities included fatigue
      (50%), constipation (48%), rash or pruritus (37%), sedation (35%), peripheral
      edema (29%), tremors (23%), peripheral neuropathy (22%), and orthostasis (16%).
      CONCLUSIONS: Thalidomide warrants further evaluation in patients with MMM,
      particularly in combination regimens, along with the investigation of newer
      analogs.

PMID- 16583432
TI  - Phase II trial of intracerebrospinal fluid etoposide in the treatment of
      neoplastic meningitis.
AB  - BACKGROUND: The purpose of the current study was to determine the toxicity and
      response of a fixed dose intracerebrospinal fluid (CSF) etoposide in the
      treatment of patients with newly diagnosed neoplastic meningitis (NM). NM
      reportedly occurs in 1% to 5% of patients with known cancer. Currently available
      treatment options are limited and provide only modest benefit. METHODS: Twenty
      seven patients (median age, 55 yrs) with clinically and cytologically documented
      NM received intra-CSF etoposide. Tumor histologies included lung (8 patients),
      breast (5 patients), primary brain tumor (4 patients), non-Hodgkin lymphoma (4
      patients), melanoma (4 patients), colon (1 patient), and prostate (1 patient).
      Concurrent involved-field radiotherapy (19 of 27 patients) or systemic
      chemotherapy (17 of 27 patients) was administered based on clinical indications.
      Etoposide was administered at a fixed dose (0.5 mg every day given 5 days per
      week every other week for 8 weeks [induction]). Patients were evaluated by CSF
      cytology and neurologic examination at the conclusion of induction therapy.
      Responding patients continued to receive etoposide (5 consecutive days every 4
      weeks) with monthly evaluations. RESULTS: Seven of 27 patients (26%) treated with
      etoposide had a cytologic response and either stable or improved neurologic
      status at the conclusion of induction. Eight patients (30%) developed disease
      progression during induction therapy and did not complete the 8-week induction
      course of therapy. At the conclusion of induction therapy, 12 patients (44%) had
      persistently positive CSF cytology, although they were clinically stable. In
      responding patients, time to neurologic disease progression ranged from 8 weeks
      to 40 weeks (median, 20 wks). Toxicity manifested as transient chemical
      arachnoiditis (5 of 27 patients; 13% of all treatment cycles). The 6-month
      neurologic disease progression-free survival was 11%. CONCLUSIONS: Etoposide
      appears to have modest activity against NM and easily managed toxicity.

PMID- 16583433
TI  - The influence of comorbidities, age, and performance status on the prognosis and
      treatment of patients with metastatic carcinomas of unknown primary site: a
      population-based study.
AB  - BACKGROUND: The authors investigated how comorbidities, age, and performance
      status were related to the choice of chemotherapy and to the prognosis of
      patients with carcinomas of unknown primary site (CUP). METHODS: Patients in
      Northern Alberta who were diagnosed with CUP during 2000 to 2003 were included (n
      = 389 patients). Survival was compared by age at diagnosis (ages <65 years, 65-74
      years, and >75 years), comorbidity score (Adult Comorbidity Evaluation-27 [ACE
      27] scores of 0-1 and >2), performance status (PS), and other explanatory
      variables, such as gender, histology, and site and number of metastases. RESULTS:
      The median age was 68 years, and the median overall survival was 12 weeks. An ACE
      27 overall comorbidity score >2 was found in 34% of patients, and a PS >2 was
      observed in 50% of patients. Multivariate analysis showed that patients who had a
      PS >/=2 and a high overall ACE-27 score had a worse prognosis. The impact of
      comorbidities on survival was limited to patients with low PS. Patients who were
      not evaluated at a cancer center were older, had a worse functional status, and
      had more moderate or severe comorbidities. Among the 257 patients who were
      evaluated at a cancer center, 108 patients received chemotherapy, and 121
      patients had a good PS (0-1). Age was the only independent variable that was
      related to the likelihood of not receiving chemotherapy among patients who had a
      good PS. The median overall survival of the 121 patients who had a good PS was
      317 days, and overall survival was not associated significantly with
      chemotherapy. A logistic regression analysis that included all patients who were
      evaluated at a cancer center identified young age, good PS, lymph node/pleural
      involvement, and few comorbidities as variables that were associated
      independently with receiving chemotherapy. CONCLUSIONS: Patients with CUP who
      were not evaluated at a cancer center were older, had a worse functional status,
      and had more moderate or severe comorbidities; this referral bias largely
      explained the differences between data from registries and from tertiary centers.
      Moderate and severe comorbidities impacted survival in patients with who had a PS
      > or =2. An age-related decline was observed in the percentage of adults with
      good PS who received chemotherapy. The current results suggested that older
      patients with CUP were under treated and that factors other than PS were involved
      in the decision to use chemotherapy for the treatment of patients with CUP.

PMID- 16583434
TI  - The fourth apolipoprotein E haplotype found in the Yoruba of Ibadan.

PMID- 16583435
TI  - Association of AKT1 haplotype with the risk of schizophrenia in Iranian
      population.
AB  - AKT-glycogen synthase kinase 3beta (GSK3beta) signaling is a target of lithium
      and has been implicated in the pathogenesis of mood disorders and schizophrenia.
      AKT1 protein level is decreased in the peripheral lymphocytes and brains of
      schizophrenic patients. The SNP2/3/4 TCG haplotype of AKT1 was associated with
      schizophrenia in patients with Northern European origin. In the present study, we
      genotyped five single nucleotide polymorphisms (SNP1-5) of AKT1 gene according to
      the original study in Iranians comprising of 321 schizophrenic patients and 383
      controls, all residing in Mashhad city, Northeastern Iran. Haplotype analysis
      showed that the frequency of a five-SNP haplotype (AGCAG) was significantly
      higher in schizophrenic patients (0.068) than that of controls (0.034) (P = 0.03
      after Bonferroni correction, OR = 2.04, CI = 1.2-3.4). In stratified analysis by
      schizophrenia subtypes, the frequency of the same haplotype was significantly
      higher in disorganized subtype (n = 78, frequency of haplotype=0.081) when
      compared with normal controls (P = 0.04 after Bonferroni correction, OR = 2.59,
      CI = 1.3-5.2). Our findings did not confirm the association of AKT1 SNP2/3/4 TCG
      haplotype with the risk of schizophrenia as reported in the original study but
      showed the evidence of association with a different haplotype, AKT1 five-SNP
      AGCAG haplotype, with the risk of schizophrenia in Iranian population.

PMID- 16583436
TI  - A family-based study of Indian subjects from Kolkata reveals allelic association
      of the serotonin transporter intron-2 (STin2) polymorphism and attention-deficit
      hyperactivity disorder (ADHD).
AB  - Serotonin transporter (SLC6A4) polymorphisms are variously implicated in
      mediating susceptibility to attention-deficit-hyperactivity disorder (ADHD), a
      highly heritable and heterogeneous disorder with onset in childhood. Since there
      has been no survey in this regard from India, a sample of 56 ADHD cases and 174
      healthy individuals from Kolkata were genotyped for the SLC6A4 promoter (5
      HTTLPR) and intron-2 (STin2) polymorphisms. We report that the observed
      distribution of allele frequencies is consonant with that expected as per Hardy
      Weinberg equilibrium proportions. Pair-wise combination of alleles comprising the
      5-HTTLPR and STin2 polymorphic systems exhibit significant (chi(2) = 14.74, df =
      1; P = 0.0001) linkage disequilibrium of low magnitude (D' = 0.269). The
      estimates of haplotype-based haplotype relative risk (HHRR) (chi(2) = 4.92, P =
      0.027; RR = 1.47; 95% CI = 1.01-2.13) and transmission disequilibrium test (TDT)
      statistics (chi(2) = 7.00, P = 0.008; OR = 3.00; 95% CI = 1.53-5.90) using a
      family-based study design, indicate significant preferential transmission of the
      STin2.12 (A12) allele to ADHD cases. Maternal inheritance of the A12 allele is
      significant in terms of the HHRR (chi(2) = 6.53, P = 0.011; RR = 2.00; 95% CI =
      1.08-3.72) and TDT (chi(2) = 8.07, P = 0.005; OR = 6.50; 95% CI = 1.76-23.98)
      suggesting a novel role for epigenetic mechanisms in the etiology of ADHD.
      Similar analyses yielded no evidence of association between the 5-HTTLPR
      polymorphism and ADHD. Studies including additional polymorphic markers, ADHD
      subjects and other ethnic groups are warranted to further substantiate the
      present findings.

PMID- 16583437
TI  - Evidence for monozygotic twin (MZ) discordance in methylation level at two CpG
      sites in the promoter region of the catechol-O-methyltransferase (COMT) gene.
AB  - Monozygotic (MZ) twin concordance for a range of psychiatric conditions is rarely
      100%. It has been suggested that epigenetic factors, such as DNA methylation, may
      account for a proportion of the variation in behavioral traits observed between
      these genetically identical individuals. In this study we have quantitatively
      assessed the methylation status of two CpG sites in the promoter region of the
      COMT gene in 12 MZ twins-pairs discordant for birth weight, but otherwise
      clinically unaffected. DNA was obtained at age 5-years using buccal swabs, and
      modified using sodium-bisulfite treatment. Methylation profiles were assessed
      using Pyrosequencing, a technology enabling the precise degree of methylation to
      be assessed at any CpG site. We found that the degree of methylation at the two
      CpG sites was highly correlated, but there was considerable variation in the
      concordance of methylation levels between MZ twin-pairs. Some MZ twin-pairs
      showed a high degree of methylation concordance, whereas others differed markedly
      in their methylation profiles. Such epigenetic variation between genetically
      identical individuals may play a key role in the etiology of psychopathology, and
      explain the incomplete phenotypic concordance observed in MZ twins.

PMID- 16583438
TI  - Assessing the extent of protein intermolecular interactions at air-water
      interfaces using spectroscopic techniques.
AB  - There is an ongoing debate about whether a protein surface film at an air-water
      interface can be regarded as a gelled layer. There is literature reporting that
      such films show macroscopic fracture behavior and a rheology comparable to three
      dimensional protein bulk-networks. If this is the case, a complete description of
      the formation of adsorbed layers should include a transition from single, freely
      moving proteins to a gelled layer. This report presents studies using
      spectroscopic techniques, such as infrared, fluorescence and neutron
      spectroscopy, or ellipsometry, to derive molecular insight in situ to
      substantiate the intermolecular networking in surface films of chicken egg
      ovalbumin. It is concluded that protein films, generated by equilibrium
      adsorption from the bulk, behave as a densely packed colloidal repulsive particle
      system, where the proteins still have a significant rotational mobility, have a
      predominantly retained globular fold, and show distinct (lateral) diffusion.
      Applied stresses on the surface film (by compressions of the interface) may
      result in protein denaturation and aggregation. This process renders a surface
      film from a colloidal particle into that of a gelled system.

PMID- 16583439
TI  - Maternal panic disorder and congenital abnormalities: a population-based case
      control study.
AB  - BACKGROUND: Maternal panic disorder in pregnancy is the most common manifestation
      of anxiety disorders in Hungary. The association between panic disorder during
      pregnancy and structural birth defects, i.e., congenital abnormalities, was
      studied. METHODS: The prevalence of maternal panic disorder in cases with
      different congenital abnormalities was compared to that of matched controls in
      the population-based Hungarian Case-Control Surveillance System of Congenital
      Abnormalities. RESULTS: Of 22,843 cases with congenital abnormalities, 210 (0.9%)
      had mothers with panic disorder during pregnancy compared to 187 (0.5%) of 38,151
      controls (adjusted prevalence odds ratio [POR] 1.6; 95% CI, 1.3-2.0). Specific
      groups of congenital abnormalities were also assessed versus controls. Cases with
      isolated cleft lip with or without cleft palate (CL/P) (adjusted POR, 3.4; 95%
      CI, 1.3-9.0) and multiple congenital abnormalities (adjusted POR, 3.0; 95% CI,
      1.2-7.2) were more likely to have had mothers with panic disorder during the
      study pregnancy. Notably, among mothers with panic disorders, the associations
      were found only in offspring of untreated mothers. CONCLUSIONS: A higher rate of
      isolated CL/P and multiple congenital abnormalities may be caused by the direct
      biological effect of panic disorder or by the interaction of maternal panic
      disorder and lifestyle factors. Antipanic drug treatment seems to have a
      protective effect for isolated CL/P and multiple congenital abnormalities. Birth
      Defects Research (Part A), 2006.

PMID- 16583441
TI  - Corroboration of mechanoregulatory algorithms for tissue differentiation during
      fracture healing: Comparison with in vivo results.
AB  - Several mechanoregulation algorithms proposed to control tissue differentiation
      during bone healing have been shown to accurately predict temporal and spatial
      tissue distributions during normal fracture healing. As these algorithms are
      different in nature and biophysical parameters, it raises the question of which
      reflects the actual mechanobiological processes the best. The aim of this study
      was to resolve this issue by corroborating the mechanoregulatory algorithms with
      more extensive in vivo bone healing data from animal experiments. A poroelastic
      three-dimensional finite element model of an ovine tibia with a 2.4 mm gap and
      external callus was used to simulate the course of tissue differentiation during
      fracture healing in an adaptive model. The mechanical conditions applied were
      similar to those used experimentally, with axial compression or torsional
      rotation as two distinct cases. Histological data at 4 and 8 weeks, and weekly
      radiographs, were used for comparison. By applying new mechanical conditions,
      torsional rotation, the predictions of the algorithms were distinguished
      successfully. In torsion, the algorithms regulated by strain and hydrostatic
      pressure failed to predict healing and bone formation as seen in experimental
      data. The algorithm regulated by deviatoric strain and fluid velocity predicted
      bridging and healing in torsion, as observed in vivo. The predictions of the
      algorithm regulated by deviatoric strain alone did not agree with in vivo data.
      None of the algorithms predicted patterns of healing entirely similar to those
      observed experimentally for both loading modes. However, patterns predicted by
      the algorithm based on deviatoric strain and fluid velocity was closest to
      experimental results. It was the only algorithm able to predict healing with
      torsional loading as seen in vivo.

PMID- 16583440
TI  - Factor analysis of obsessive-compulsive disorder YBOCS-SC symptoms and
      association with 5-HTTLPR SERT polymorphism.
AB  - Symptoms defining obsessive-compulsive disorder (OCD) are diverse. Factor
      analyses of OCD symptoms have been used to evaluate obsessive-compulsive
      phenotypes that are thought to be more homogenous than the macro phenotype. There
      is evidence that three factors (symmetry/ordering, obsessions/checking, and
      hoarding) are familial and preliminary evidence that repetitive rituals are
      associated with a functional polymorphism in the promotor region of the serotonin
      transporter gene (5-HTTLPR). The goal of this study was to examine relationships
      between OCD symptom dimensions and 5-HTTLPR. We genotyped 153 subjects who met
      DSM-IV criteria for OCD. We used the Yale-Brown obsessive-compulsive scale
      symptom checklist (YBOCS-SC) to assess OCD symptoms. Using principle components
      analysis, we derived four factors from the 13 symptom categories of the YBOCS-SC
      in this patient sample, which replicated previous factor analyses of this scale.
      The frequencies of the S allele and the SS genotype were associated with the
      second factor including obsessions regarding symmetry and compulsions involving
      repeating, counting, and ordering/arranging. This study may contribute to
      understanding of molecular genetic features underlying the appearance of symptom
      clusters in OCD.

PMID- 16583442
TI  - Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: Promoted
      tendon-to-bone healing and opposed corticosteroid aggravation.
AB  - Stable gastric pentadecapeptide BPC 157 (BPC 157, as an antiulcer agent in
      clinical trials for inflammatory bowel disease; PLD-116, PL 14736, Pliva, no
      toxicity reported) alone (without carrier) ameliorates healing of tendon and
      bone, respectively, as well as other tissues. Thereby, we focus on Achilles
      tendon-to-bone healing: tendon to bone could not be healed spontaneously, but it
      was recovered by this peptide. After the rat's Achilles tendon was sharply
      transected from calcaneal bone, agents [BPC 157 (10 microg, 10 ng, 10 pg), 6alpha
      methylprednisolone (1 mg), 0.9% NaCl (5 mL)] were given alone or in combination
      [/kg body weight (b.w.) intraperitoneally, once time daily, first 30-min after
      surgery, last 24 h before analysis]. Tested at days 1, 4, 7, 10, 14, and 21 after
      Achilles detachment, BPC 157 improves healing functionally [Achilles functional
      index (AFI) values substantially increased], biomechanically (load to failure,
      stiffness, and Young elasticity modulus significantly increased),
      macro/microscopically, immunohistochemistry (better organization of collagen
      fibers, and advanced vascular appearance, more collagen type I). 6alpha
      Methylprednisolone consistently aggravates the healing, while BPC 157
      substantially reduces 6alpha-methylprednisolone healing aggravation. Thus, direct
      tendon-to-bone healing using stabile nontoxic peptide BPC 157 without a carrier
      might successfully exchange the present reconstructive surgical methods.

PMID- 16583443
TI  - Chondrocyte gene expression in osteoarthritis: Correlation with disease severity.
AB  - Osteoarthritis is characterized by a progressive degradation of cartilage
      structure and function. This study tests the hypothesis that disease severity is
      characterized by alterations in expression of cartilage-specific genes for
      aggrecan and collagen type II. Cartilage, discarded from six subjects undergoing
      knee replacement, was subdivided into homogeneous portions by the surgeon
      according to the Outerbridge classification. For four subjects, it was possible
      to separate the tissue into two or three fractions with different disease
      severity. Portions of each sample were prepared either for histological analysis
      and ranking according to the Mankin system or for RNA extraction. Quantitative,
      competitive RT-PCR assays were used for measurement of mRNA for aggrecan,
      collagen type II, and glyceraldehyde-3-phosphate dehydrogenase. Clinical grading
      was correlated with histological score (Spearman r = 0.60, p = 0.043). There was
      a striking decrease in expression of aggrecan and collagen II that was correlated
      with increase in the grade in regions of cartilage within an individual subject.
      In the series of 12 samples, there was an inverse correlation between aggrecan
      expression and osteoarthritis grade (Spearman r = -0.59, p = 0.042). In
      conclusion, there was an inverse relationship between regional disease severity
      in osteoarthritis and expression of aggrecan. Use of quantitative, competitive RT
      PCR is practical for assessment of chondrocyte gene signatures.

PMID- 16583444
TI  - Nondestructive evaluation of osteogenic differentiation in tissue-engineered
      constructs.
AB  - Conventional measurements of osteogenesis in tissue-engineered constructs are
      destructive to living cells and incapable to provide three-dimensional
      information. In the present study, noninvasive magnetic resonance (MR) microscopy
      was used to evaluate osteogenic differentiation in vitro in human mesenchymal
      stem cell-based tissue-engineered constructs. The constructs were prepared by
      seeding the cells (10(6)cells/ml) on 4 x 4 x 4 mm gelatin sponge cubes and
      subsequently exposing them to osteogenic differentiation or basic medium. During
      the 4-week experiment, alkaline phosphatase (ALP) activity and calcium content of
      differentiated constructs were significantly increased compared to the basic
      medium controls. The T1, T2, and apparent diffusion coefficient (ADC) of
      differentiated constructs were significantly lower than those of the control
      group at each time point (p < 0.05). The MR parameters of constructs were
      significantly correlated to their ALP activities (r to T1, T2, and ADC = -0.57, 
      0.78, and -0.81, respectively) and calcium content (r to T1, T2, and ADC = 0.48,
      0.90, and 0.92, respectively) measured by biochemical techniques. MR microscopy
      can be a promising tool for noninvasive assessment of osteogenic differentiation
      and to provide three-dimensional information about tissue-engineered constructs.

PMID- 16583445
TI  - Improved anchorage in osteoporotic vertebrae with new implant designs.
AB  - The goal of our study was to evaluate two newly developed implant designs and
      their behavior in terms of subsidence in lumbar vertebral bodies under cyclic
      loading. The new implants were evaluated in two different configurations (two
      small prototypes vs. one large prototype with similar load-bearing area) in
      comparison to a conventional screw-based implant (MACS TL). A pool of 13 spines
      with a total of 65 vertebrae was used to establish five testing groups of similar
      bone mineral density (BMD) distribution with eight lumbar vertebrae each. In
      additional to BMD assessment via dual-energy X-ray absorptiometry, cancellous BMD
      and structural parameters were determined using a new generation in vivo 3D-pQCT.
      The specimens were loaded sinusoidally in force control at 1 Hz for 1000 cycles
      at three load levels (100, 200, and 400 N). A survival analysis using the number
      of cycles until failure (Cox regression with covariates) was applied to reveal
      differences between implant groups. All new prototype configurations except the
      large cylinder survived significantly longer than the control group. The number
      of cycles until failure was significantly correlated with the structural
      parameter Tb.Sp. and similarly with the cancellous BMD for three of five
      implants. In both large prototypes the cycle number until failure significantly
      correlated with the preoperative distance to the upper endplates. Although the
      direct relationship between bone structure or density and mechanical breakage
      behavior cannot be conclusively proven, all the prototypes adapted for poor bone
      structure performed better than the comparable conventional implant.

PMID- 16583446
TI  - Hyaluronic acid attenuates osteoarthritis development in the anterior cruciate
      ligament-transected knee: Association with excitatory amino acid release in the
      joint dialysate.
AB  - We previously reported increased release of the excitatory amino acid (EAA)
      neurotransmitters, glutamate and aspartate, during the early stage of
      experimental osteoarthritis (OA). Our present objective was to study the effect
      of intraarticular injection of hyaluronic acid (HA) on OA development, and to
      analyze concomitant changes in EAA levels in dialysates of anterior cruciate
      ligament-transected (ACLT) knee joints. OA was induced in Wistar rats by ACLT of
      one hindlimb; the knee of the other hindlimb was used as the sham-operated
      control. HA group (n = 12) were injected intraarticularly in the ACLT knee with 1
      mg of HA once a week for 5 consecutive weeks, starting at 8 weeks after surgery.
      Saline group (n = 12) were injected as above with normal saline. The sham
      operated group, underwent arthrotomy, but not ACLT, and received no treatment (n
      = 14). Twenty weeks after surgery, knee joint dialysates were collected by
      microdialysis and EAA levels assayed by high-performance liquid chromatography,
      and gross morphological examination and histopathological evaluation were
      performed on the medial femoral condyles and synovia. Rats receiving
      intraarticular HA injections showed a significantly lower degree of cartilage
      degeneration on the medial femoral condyle at both the macroscopic level and on
      the Mankin grading scale than rats receiving saline injections. Intraarticular HA
      treatment also suppressed synovitis. Moreover, glutamate and aspartate levels
      were significantly reduced in the HA group compared to the saline group.
      Intraarticular injection of HA limits articular cartilage and synovium damage and
      OA formation, and, in parallel, reduces EAA levels in ACLT joint dialysates. This
      study suggests that the underlying mechanism of the anti-inflammatory effect of
      HA is to inhibit glutamate and aspartate release in ACLT knee joints, which
      attenuates the early development of OA.

PMID- 16583447
TI  - Effect of the iliotibial band on knee biomechanics during a simulated pivot shift
      test.
AB  - The purpose of this study was to evaluate the effect of the iliotibial band (ITB)
      on the kinematics of anterior cruciate ligament (ACL) intact and deficient knees
      and also on the in situ force in the ACL during a simulated pivot shift test. A
      combination of 10 N-m valgus and 5 N-m internal tibial torques was applied to 10
      human cadaveric knees at 15 degrees, 30 degrees, 45 degrees, and 60 degrees of
      flexion using a robotic/universal force-moment sensor testing system. ITB forces
      of 0, 22, 44, and 88 N were also applied. An 88 N ITB force significantly
      decreased coupled anterior tibial translation of ACL deficient knees by 32%-45%
      at high flexion angles, but did not have a significant effect at low flexion
      angles. Further, an 88 N ITB force significantly decreased in situ forces in the
      ACL at all flexion angles by 23%-40%. These results indicate that during the
      pivot shift test, the ITB can improve tibial reduction at high flexion angles
      while not affecting subluxation at low flexion angles. Additionally, the action
      of the ITB as an ACL agonist suggests that its use as an ACL graft might hinder
      knee stability in response to rotatory load.

PMID- 16583448
TI  - Healing of articular cartilage defects. An experimental study of vascular and
      minimal vascular microenvironment.
AB  - The repair potential in a chondral defect with (treatment A) or without access to
      bone marrow elements (treatment B) at the basis of the defect sealed by a rim
      sutured periosteal flap was studied using adult New Zealand rabbits (22 weeks) as
      an experimental model. At sacrifice, macroscopical changes, synovial fluid
      contents, degree of filling, thickness of the cartilage rim, and the subchondral
      bone were evaluated. Histomorphometric measurements of extent of filling (mainly
      fibrous tissue) of the defect at 36 weeks postoperatively, showed 50% filling in
      treatment A compared with 33% in treatment B (p = 0.011). A difference in height
      of the cartilage rim between the experimental groups and sham-control was
      measured ( p = 0.005). Cartilage degeneration was observed at the cartilage rim
      of the original defect, and included loss of chondrocytes and disruption of
      surface continuity in both experimental groups. In addition, treatment A resulted
      in a significantly increased thickness of the subchondral bone in the defect in
      comparison to treatment B at 2 weeks and at 36 weeks (p = 0.021). The increased
      thickness of the subchondral bone may be of concern for the bone marrow
      stimulation techniques regarding the long-term outcome.

PMID- 16583449
TI  - Cartilage tissue engineering by expanded goat articular chondrocytes.
AB  - In this study we investigated whether expanded goat chondrocytes have the
      capacity to generate cartilaginous tissues with biochemical and biomechanical
      properties improving with time in culture. Goat chondrocytes were expanded in
      monolayer with or without combinations of FGF-2, TGF-beta1, and PDGFbb, and the
      postexpansion chondrogenic capacity assessed in pellet cultures. Expanded
      chondrocytes were also cultured for up to 6 weeks in HYAFF-M nonwoven meshes or
      Polyactive foams, and the resulting cartilaginous tissues were assessed
      histologically, biochemically, and biomechanically. Supplementation of the
      expansion medium with FGF-2 increased the proliferation rate of goat chondrocytes
      and enhanced their postexpansion chondrogenic capacity. FGF-2-expanded
      chondrocytes seeded in HYAFF-M or Polyactive scaffolds formed cartilaginous
      tissues with wet weight, glycosaminoglycan, and collagen content, increasing from
      2 days to 6 weeks culture (up to respectively 2-, 8-, and 41-fold). Equilibrium
      and dynamic stiffness measured in HYAFF M-based constructs also increased with
      time, up to, respectively, 1.3- and 16-fold. This study demonstrates the
      feasibility to engineer goat cartilaginous tissues at different stages of
      development by varying culture time, and thus opens the possibility to test the
      effect of maturation stage of engineered cartilage on the outcome of cartilage
      repair in orthotopic goat models.

PMID- 16583450
TI  - Bone loss dynamics result in trabecular alignment in aging and ovariectomized
      rats.
AB  - Because of the destructive nature of techniques used to measure bone morphometry,
      studies of architectural changes and bone loss have utilized cross-sectional
      study designs, with all its inherent limitations in nuances. Here, the results of
      a longitudinal study using in vivo micro-CT are presented elucidating the
      dynamics of bone loss and architectural adaptation in rat models of aging and
      postmenopausal bone loss. Using 3-D methodology, we observed the changes in bone
      architecture in the proximal tibia of normally aging and ovariectomized rats for
      54 weeks. Spatial patterns in bone resorption were observed that were similar for
      both groups. Remaining trabeculae increased in thickness or were remodeled into
      new trabecular structures, especially in the ovariectomized animals. The
      combination of bone loss and bone formation resulted in alignment of trabeculae
      across the growth plate. Cortical modeling that was associated with growth
      continued after cessation of longitudinal growth in the ovariectomized animals,
      resulting in shape changes of the proximal tibia. The organized nature of the
      changes in bone architecture that occurred after ovariectomy and the high
      similarity with the changes observed in the normally aging animals, suggest that
      estrogen depletion resulted in an acceleration of a normal bone adaptation
      process. The observed aligning of trabeculae suggests regulation through
      mechanical loading.

PMID- 16583451
TI  - Determination and pharmacokinetic study of bergenin in rat plasma by RP-HPLC
      method.
AB  - A validated reversed-phase high-performance liquid chromatographic (RP-HPLC)
      method was developed for the determination of bergenin in rat plasma. Bergenin in
      rat plasma was extracted with methanol, which also acted as a deproteinization
      agent. Chromatographic separation of bergenin was performed on a C(18) column,
      with a mobile phase of methanol-water (22:78, v/v) at a flow-rate of 0.8 mL/min
      and an operating temperature of 40 degrees C, and UV detection was set at 220 nm.
      The calibration curve was linear over the range 0.25-50 microg/mL (r = 0.9990) in
      rat plasma. The limit of quantification was 0.25 microg/mL using a plasma sample
      of 100 microL. The extraction recoveries were 83.40 +/- 6.02, 81.49 +/- 2.40 and
      72.51 +/- 2.64% at concentrations of 0.5, 5 and 50 microg/mL, respectively. The
      intra-day and inter-day precision and accuracy were validated by relative
      standard deviation (RSD%) and relative error (RE%), which were in the ranges 3.74
      9.91 and -1.6-8.0%. After intravenous administration to rats at the dose of 11.25
      mg/kg, the plasma concentration-time curve of bergenin was best conformed to a
      two-compartment open model. The main pharmacokinetic parameters indicated that
      bergenin exhibited a wide distribution and moderate elimination velocity in rat.

PMID- 16583452
TI  - Determination of foscarnet (trisodium phosphonoformate) in pharmaceutical
      preparations by high-performance liquid chromatography with ultraviolet
      detection.
AB  - An isocratic high-performance liquid chromatographic method with UV detection has
      been developed and validated for the quantitative determination of foscarnet in
      isoosmotic sodium chloride aqueous solution. The mobile phase consisted of
      mixture of methanol:water (30:70 v/v), containing 1 mm tetrahexylammonium
      hydrogen sulphate at pH 5.80. The analyte was separated on a reversed-phase C(18)
      column packed with 4 microm spherical particles of octadecylsilane.
      Hydrochlorothiazide was used as internal standard. UV detection at 232 nm allowed
      a quantification limit of 50 microg/mL. The assay was linear from 50 to 4000
      microg/mL. The coefficient of variation was < or =2.52% for intra-assay precision
      and < or =3.49% for inter-assay precision. The deviation from the nominal value
      ranged from -0.57 to 0.47% for the same-day accuracy and from -0.75 to 3.06% for
      day-to-day accuracy.

PMID- 16583453
TI  - HPLC study of tissue distribution of loganin in rats.
AB  - A rapid, sensitive and selective high performance liquid chromatography (HPLC)
      method was developed and validated for determination of loganin in rat tissues.
      Samples were prepared based on a simple protein precipitation. Separation of
      loganin was achieved on a reversed-phase C(18) column (250 x 4.6 mm, 5 microm)
      with a mobile phase consisting of acetonitrile and water (16:84, v/v) at a flow
      rate of 1.0 mL/min. The detection wavelength was set at 236 nm and the
      temperature of the column was kept at 30 degrees C. The method was applied to
      study tissue distribution of loganin in rats after a single administration of
      loganin at a dose of 20 mg/kg. The highest level was observed in kidney, then in
      stomach, lung and small intestine. The lowest level was found in brain. The peak
      levels were attained at 90 min in most tissues. It was indicated that kidney was
      the major distribution tissue of loganin in rats, and that loganin had difficulty
      in crossing the blood-brain barrier. It was also found there was no long-term
      accumulation of loganin in rat tissues.

PMID- 16583454
TI  - Simultaneous determination of honokiol and magnolol in Magnolia officinalis by
      liquid chromatography with tandem mass spectrometric detection.
AB  - An optimized high-performance liquid chromatographic method coupled with tandem
      mass spectrometric detection (LC-MS/MS) was developed for the simultaneous
      determination of honokiol and magnolol in Magnolia officinalis. Honokiol and
      magnolol were separated from the extracts using a reversed-phase C(18) column
      with a mobile phase consisted of acetonitrile and water (75:25, v/v) at a flow
      rate of 0.8 mL/min. Selected reaction monitoring (SRM) mode was used for all
      sample quantification by the precursor-ion/product ion pair m/z 265 --> m/z 224
      for honokiol and m/z 265 --> m/z 247 for magnolol. Validation data showed that
      this method has good linearity (r(2) > 0.995) over the concentration range of
      0.0025-0.5 microg/mL for honokiol and magnolol, and both intra- and inter-day
      variability were acceptable within 15% at the lowest concentrations for this
      method. This proposed method provides excellent specificity, higher sensitivity
      and shorter run time than conventional methods and was applied successfully to
      determine the contents of honokiol and magnolol in M. officinalis.

PMID- 16583455
TI  - Rapid column-switching liquid chromatography/mass spectrometric assay for DHEA
      sulfate in the plasma of patients with Alzheimer's disease.
AB  - A simple and highly sensitive method for the quantification of
      dehydroepiandrosterone-3-sulfate (DHEAS) in human plasma was developed. DHEAS was
      directly determined in plasma using column-switching liquid chromatography/mass
      spectrometry (LC-MS). The plasma was filtered with a membrane filter. The
      filtrate was injected onto a pre-column without further sample preparation such
      as extraction or derivatization. The pre-column was washed with an aqueous
      solution to remove interference and the analyte was eluted into a reversed-phase
      C(18) analytical column for separation and detection using a column-switching
      valve. The calibration range of DHEAS was 0.01-10 micromol/L, and the linearity
      of the method was 0.999. The limit of detection (LOD) at a signal-to-noise (S/N)
      ratio of 3 was 5 nmol/L. The accuracy and precision (%CV) were less than 10% in
      within-day and day-to-day variations. To explore the relationship between
      Alzheimer's disease and the DHEAS level in human plasma, the concentrations of
      DHEAS in female patients with Alzheimer's disease (n = 20) and in normal female
      subjects (n = 20) were measured. The level of DHEAS was significantly decreased
      in the plasma of patients with Alzheimer's disease (p < 0.0002) compared with
      that in normal subjects. From the results, we concluded that our method is
      sufficiently sensitivity and reliability for the quantification of DHEAS in
      clinical samples. Plasma DHEAS concentration could be an important marker to
      understand the pathogenesis of Alzheimer's disease.

PMID- 16583456
TI  - Determination of coenzyme Q10 in human seminal plasma by high-performance liquid
      chromatography and its clinical application.
AB  - A high-performance liquid chromatographic (HPLC) method for the analysis of
      coenzyme Q10 (CoQ10) in human seminal plasma was developed and applied to
      investigate its clinical significance as a reference index relating to oxidative
      stress and infertile status of spermatozoa. After precipitation of proteins in
      seminal plasma with methanol, CoQ10 and coenzyme Q9 (CoQ9; internal standard)
      were extracted with hexane. The supernatant after centrifugation was evaporated
      to dryness with nitrogen at 45 degrees C. The residue was re-dissolved in
      isopropanol. HPLC separation of the sample solution was performed on a
      Lichrospher C(18) column with a mobile phase composed of isopropanol-methanol
      tetrahydrofuran in the ratio of 55:39:6 (v/v/v) at a flow rate of 1.0 mL/min.
      Under the chromatographic conditions described, the CoQ10 and CoQ9 had retention
      times of approximately 5.83 and 4.97 min, respectively. The peaks were detected
      at UV 275 nm. Good separation and detectability of CoQ10 in human seminal plasma
      were obtained. The method was linear in the range 0.01-10.00 microg/mL. The
      relative standard deviations within- and between-assay for CoQ10 analysis were
      0.85 and 1.86%, respectively. The average recoveries were 94.1-99.0% for the
      human seminal plasma samples. The CoQ10 levels in seminal plasma of 195 patients
      and 23 control subjects were studied. CoQ10 concentrations in the two populations
      were: 37.1 +/- 12.2 ng/mL in the fertile group and 48.5 +/- 20.4 ng/mL in the
      infertile group. The large difference (p < 0.01) between the fertile and
      infertile populations is evident.

PMID- 16583457
TI  - High-performance liquid chromatographic method for the determination and
      pharmacokinetic study of wogonoside in rat serum after oral administration of
      traditional Chinese medicinal preparation Huang-Lian-Jie-Du decoction.
AB  - A high-performance liquid chromatographic method for the determination of
      wogonoside in plasma of rats administrated orally with the traditional Chinese
      medicinal preparation Huang-Lian-Jie-Du decoction was developed. Sample
      preparation was carried out by protein precipitation with a mixture of
      acetonitrile and methanol (1:1, v/v). The extracted sample was separated on a
      Hypersil C(18) (150 x 5 mm i.d., 5 microm) analytical column by linear gradient
      elution using 0.05% (v/v) phosphoric acid (containing 5 mm sodium dihydrogen
      phosphate) and acetonitrile as mobile phase at a flow rate of 1.5 mL/min. The
      eluate was detected using a UV detector at 276 nm. The assay was linear over the
      range 0.109-7.0 microg/mL (R(2) = 0.9999, n = 5). Mean recovery was determined as
      98.39%. Intra- and inter-day precisions (RSD) were < or =7.59%. The limit of
      quantitation was 0.109 microg/mL. After validation, the HPLC method developed was
      applied to investigate the preliminary pharmacokinetics of wogonoside in rat
      after oral administration of Huang-Lian-Jie-Du decoction.

PMID- 16583458
TI  - Determination of ligustilide in rat blood and tissues by capillary gas
      chromatography/mass spectrometry.
AB  - A gas chromatography/mass spectrometry (GC/MS) method was developed to study the
      pharmacokinetics of ligustilide following oral administration to rats. The method
      was used for the analysis of samples taken from rats. Biological samples were
      prepared by liquid-liquid extraction (LLE) using an n-hexane-ether (2:1) solvent
      mixture for a sample clean-up step and analyzed by GC/MS with a quadrupole MS
      detector in selected ion monitoring mode (m/z 190). The calibration curves were
      linear over the concentration range 0.172-8.60 microg/mL (r > 0.99) for blood
      samples and a different range (r > 0.99) for different tissue samples. The limit
      of detection (LOD) was 1.0 ng/mL or 1.0 ng/g (three times the signal-noise
      ratio). Within- and between-day precision expressed as the relative standard
      deviation (RSD) for the method was 1.58-3.88 and 2.99-4.91%, respectively. The
      recovery for all samples was >80%, except for liver samples (>70%). The main
      pharmacokinetic parameters obtained were: T(max) = 0.65 +/- 0.07 h, C(max) = 1.5
      +/- 0.2 microg/mL, AUC = 34 +/- 6 h microg/mL and K(a) = 3.5 +/- 0.6/h. The
      experimental results showed that ligustilide was easily absorbed, but its
      elimination was slow, from 3 to 12 h after oral administration. The
      concentrations of ligustilide in rat cerebellum, cerebrum, spleen and kidney were
      higher than those in other organs.

PMID- 16583459
TI  - Comparison of enzyme-linked immunosorbent assay with liquid chromatography-tandem
      mass spectrometry for the determination of diethylstilbesterol residues in
      chicken and liver tissues.
AB  - A competitive enzyme-linked immunosorbent assay (ELISA) was developed for the
      quantitative detection of the diethylstilbesterol (DES). Polyclonal rabbit
      antisera, raised against protein conjugate diethylstilbesterol-mono-caroxyl
      propyl-ethyl-bovine-serum-albumin (DES-MCPE-BSA), were utilized in immobilized
      antibody-based and competitive immunoassays. Assay conditions, including
      concentrations of antisera and horseradish peroxidase, (HRP)-DES, were optimized.
      The effects of incubation time, surfactant concentration, ionic strength and pH
      of the medium were also investigated. The typical calibration curve gave an
      average IC(50) value of 2.4 ng/mL, calibration range from 0.2 to 30.5 ng/mL and a
      detection limit of 0.07 ng/mL. The specificity of the assay was tested against
      DES structurally related compounds, and the assay proved highly selective for
      DES. Assay performance was validated using spiked chicken meat and liver tissue
      samples. Moreover, it was compared with liquid chromatography-tandem mass
      spectrometry. The ion pair for quantification of DES was m/z 267.4/251.4, and the
      linear equation of DES was y = 0.1033x + 0.0126 (r = 0.9960). The two analytical
      methods can be applied to monitor DES and other steroid residues in foods.

PMID- 16583460
TI  - Determination of cocaine and cocaethylene in urine by solid-phase microextraction
      and gas chromatography-mass spectrometry.
AB  - In order to evaluate recent cocaine exposure or its coingestion with ethanol, a
      simple and sensitive solid-phase microextraction (SPME) procedure for
      determination of cocaine and cocaethylene in urine was developed and validated. A
      polydimethylsiloxane fibre (100 microm) was submersed in the urine sample for 20
      min under magnetic stirring after alkalinization with solid buffer
      (NaHCO(3):K(2)CO(3), 2:1). Gas chromatography-mass spectrometry (GC-MS) was used
      to identify and quantify the analytes in selected ion monitoring mode (SIM). The
      limits of quantification were 5.0 ng/mL for both analytes. Good inter- and intra
      assay precision was also observed (coefficient of variation <9%).

PMID- 16583461
TI  - HDAC inhibitor treatment of hepatoma cells induces both TRAIL-independent
      apoptosis and restoration of sensitivity to TRAIL.
AB  - Hepatocellular carcinoma (HCC) displays a striking resistance to chemotherapeutic
      drugs or innovative tumor cell apoptosis-inducing agents such as tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL). Recently, we found 2 histone
      deacetylase inhibitors (HDAC-I), valproic acid and ITF2357, exhibiting inherent
      therapeutic activity against HCC. In TRAIL-sensitive cancer cells, the mechanism
      of HDAC-I-induced cell death has been identified to be TRAIL-dependent by
      inducing apoptosis in an autocrine fashion. In contrast, in HCC-derived cells, a
      prototype of TRAIL-resistant tumor cells, we found a HDAC-I-mediated apoptosis
      that works independently of TRAIL and upregulation of death receptors or their
      cognate ligands. Interestingly, TRAIL resistance could be overcome by a
      combinatorial application of HDAC-I and TRAIL, increasing the fraction of
      apoptotic cells two- to threefold compared with HDAC-I treatment alone, whereas
      any premature HDAC-I withdrawal rapidly restored TRAIL resistance. Furthermore, a
      tumor cell-specific downregulation of the FLICE inhibitory protein (FLIP) was
      observed, constituting a new mechanism of TRAIL sensitivity restoration by HDAC
      I. In contrast, FLIP levels in primary human hepatocytes (PHH) from different
      donors were upregulated by HDAC-I. Importantly, combination HDAC-I/TRAIL
      treatment did not induce any cytotoxicity in nonmalignant PHH. In conclusion,
      HDAC-I compounds, exhibiting a favorable in vivo profile and inherent activity
      against HCC cells, are able to selectively overcome the resistance of HCC cells
      toward TRAIL. Specific upregulation of intracellular FLIP protein levels in
      nonmalignant hepatocytes could enhance the therapeutic window for clinical
      applications of TRAIL, opening up a highly specific new treatment option for
      advanced HCC.

PMID- 16583462
TI  - Five oximes (K-27, K-33, K-48, BI-6 and methoxime) in comparison with
      pralidoxime: survival in rats exposed to the organophosphate paraoxon.
AB  - Oximes are cholinesterase reactivators used in organophosphorus poisoning.
      Clinical experience with pralidoxime (PRX) and other oximes is disappointing and
      their routine use has been questioned. In addition it is known that not all
      oximes are equally effective against all existing organophosphorus compounds.
      There is a demand for broad-spectrum reactivators with a higher efficacy than
      PRX. Based on our previous in vitro work the protection conferred by the various
      new oximes against inhibition by paraoxon as quantified by the IC(50) shift (nM
      increase in the IC(50) of the inhibitor per microM oxime present) is: 0.3 (PRX),
      0.4 (methoxime; MMC-4), 1 (K-33), 1.2 (BI-6), 1.5 (K-48) and 3.7 (K-27). The
      purpose of the study was to quantify in vivo the extent of oxime-conferred
      protection, using paraoxon (POX) as a cholinesterase inhibitor and to test
      whether in vitro efficacy translates to protection from mortality. There were
      seven groups of six rats in each cycle of the experiment. Group 1 (G1) received 1
      micromol POX (approximately LD(75)), the other groups (G2-G7) received 1 micromol
      POX + of one the six reactivators. The animals were monitored for 48 h and the
      time of mortality was recorded. The procedure was repeated five times (cycles).
      All substances were applied i.p. The experiments were repeated using 2, 3, 5 and
      10 micromol POX. Mortality data were compared and hazards ratios (relative risks)
      ranked using the Cox proportional hazards model using POX dose and group
      (reactivator) as time-independent covariables. The relative risk of death
      estimated by Cox analysis (95% CI) in oxime treated animals when compared with
      untreated animals, adjusted for POX dose (high/low) was K-27: 0.26 (0.19-0.35); K
      48: 0.34 (0.25-0.45); methoxime: 0.38 (0.29-0.50); BI-6: 0.53 (0.41-0.69); PRX:
      0.70 (0.54-0.91); K-33: 0.82 (0.63-1.07). It is concluded that K-27 and K-48 are
      the most promising new oximes. The compounds with the best results in vitro also
      confer the best protection in vivo. Further testing using methyl- and propyl
      organophosphates are needed.

PMID- 16583463
TI  - Childhood onset systemic sclerosis: classification, clinical and serologic
      features, and survival in comparison with adult onset disease.
AB  - OBJECTIVE: To describe the differences between patients with systemic sclerosis
      (SSc) having childhood versus adult onset evaluated at a single medical center.
      METHODS: Patients were divided into those with childhood onset (first SSc symptom
      or finding before age 16 yrs) and those with early adult and late adult onset.
      The 3 groups were compared with respect to disease classification, clinical,
      laboratory and serologic data, and survival. RESULTS: One hundred eleven
      childhood onset SSc cases seen between 1960 and 2003 were compared with 2559
      adult onset SSc cases (1087 with onset age 16-40 and 1472 with onset after age 40
      yrs) first evaluated between 1972 and 2001. Age distribution at onset was
      unimodal, suggesting that childhood disease is part of the spectrum of adult
      onset SSc. A significantly greater proportion of childhood onset patients had
      overlap syndromes, most frequently with polymyositis-dermatomyositis (PM-DM), and
      skeletal muscle involvement. Children with diffuse cutaneous (dc) SSc had
      significantly lower maximum mean total skin thickness scores than adult patients
      with dcSSc. Renal involvement was uncommon in childhood onset cases, and the
      frequency increased with age of onset. Serum anti-PM-Scl and anti-U1RNP
      antibodies were detected significantly more frequently in childhood than in adult
      onset cases. In contrast, anti-RNA polymerase III and anticentromere antibodies
      were found significantly more frequently in adults. Survival was significantly
      better among childhood than all adult onset cases combined, but similar to
      survival in young adult onset SSc cases. Scleroderma heart disease was a frequent
      cause of death among children with SSc. CONCLUSION: Patients with juvenile onset
      SSc more frequently have an overlap syndrome with PM-DM, higher frequency of
      skeletal muscle involvement, serum anti-PM-Scl and anti-U1RNP antibody, fatal
      cardiac disease, and improved survival compared with adult onset SSc cases.

PMID- 16583464
TI  - Evaluation of the comparative efficacy and tolerability of rofecoxib and naproxen
      in children and adolescents with juvenile rheumatoid arthritis: a 12-week
      randomized controlled clinical trial with a 52-week open-label extension.
AB  - OBJECTIVE: To compare the safety and efficacy of rofecoxib* to naproxen for the
      treatment of juvenile rheumatoid arthritis (JRA). METHODS: This was a 12-week,
      multicenter, randomized, double-blind, double-dummy, active comparator
      controlled, non-inferiority study with a prespecified 52-week open-label active
      comparator-controlled extension. Children (ages 2-11 yrs) and adolescents (ages
      12-17 yrs) received lower-dose (LD)-rofecoxib [0.3 mg/kg/day up to 12.5 mg/day
      (base study only)]; or higher-dose (HD)-rofecoxib (0.6 mg/kg/day up to 25 mg/day)
      or naproxen 15 mg/kg/day as oral suspensions. Adolescents received daily
      rofecoxib (LD) 12.5 (base study only) or (HD) 25 mg, or naproxen 15 mg/kg/day
      (maximum 1,000 mg/day) as tablets. The primary endpoint was the time-weighted
      average proportion of patients meeting the American College of Rheumatology
      Pediatric-30 (ACR Pedi 30) response criteria. A prespecified bound for the 95%
      confidence interval for the ratio of the percentage of ACR Pedi 30 responders was
      used to assess non-inferiority of treatment response between groups. Safety was
      assessed throughout the study. RESULTS: A total of 310 patients ages 2-17 years
      (181 (3/4) age 11) were randomized to receive LD-rofecoxib (N=109), HD-rofecoxib
      (N=100), or naproxen (N=101). The ACR Pedi 30 response rates following 12 weeks
      of treatment were 46.2%, 54.5%, and 55.1%, respectively. The relative rates of
      response compared to naproxen were 0.81 (95% CI 0.61, 1.07) and 0.98 (95% CI
      0.76, 1.26) for LD- and HD-rofecoxib, respectively. Both rofecoxib doses were not
      inferior to naproxen. Patients (N=227) entering the extension received HD
      rofecoxib or naproxen with efficacy maintained during the extension. All
      treatments were generally well tolerated throughout the study. CONCLUSION: Daily
      treatment of JRA patients with rofecoxib up to 12.5 or 25 mg was well tolerated,
      providing sustained clinical effectiveness comparable to naproxen 15 mg/kg. *On
      September 30, 2004, Merck & Co., Inc. announced the voluntary worldwide
      withdrawal of rofecoxib from the market.

PMID- 16583465
TI  - Laboratory and imaging studies used by French rheumatologists to evaluate
      patients with early arthritis.
AB  - OBJECTIVE: To conduct a practice survey of laboratory and imaging studies used by
      French rheumatologists to identify the cause of recent-onset arthritis. METHODS:
      We selected a random sample of 210 rheumatologists, who were asked to recruit all
      patients with recent-onset arthritis (at least one joint involved, for less than
      one year) during a 2 week period, and to record laboratory and imaging studies
      performed. Results were analyzed in the overall group, in diagnostic subgroups,
      and in clinical presentation subgroups. RESULTS: The 119 rheumatologists who
      participated recruited 104 patients. Investigations done in 50% to 75% of
      patients were blood cell counts; erythrocyte sedimentation rate; serum assays of
      C-reactive protein, rheumatoid factors, antinuclear antibodies; and hand
      radiographs. Investigations in 50% to 74% of patients were serum ASAT/ALAT,
      creatinine, and uric acid; and foot radiographs. Finally, 25% to 49% of patients
      were tested for proteinuria; antikeratin antibodies; hepatitis B, hepatitis C,
      and Lyme serologies; creatine phosphokinase; blood iron; HLA-B27; and radiographs
      of chest and pelvis. No differences were found between investigations in patients
      with suspected rheumatoid arthritis and/or undifferentiated arthritis and those
      in other patients. In contrast, suspected diagnoses and presence of
      extraarticular manifestations classically associated with specific diseases
      modified the selection of investigations. CONCLUSION: Although considerable
      variability occurred, our study suggests that a limited panel of laboratory and
      imaging studies is performed in at least 25% of patients with recent-onset
      arthritis, regardless of clues suggesting a specific diagnosis.

PMID- 16583466
TI  - A phase I study assessing the safety, clinical response, and pharmacokinetics of
      an experimental infliximab formulation for subcutaneous or intramuscular
      administration in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To assess safety, clinical response, and pharmacokinetics of
      subcutaneous (SC) and intramuscular (IM) doses of an experimental formulation of
      infliximab [including experimental SC doses following administration of
      commercially-formulated intravenous (IV) infliximab] in patients with rheumatoid
      arthritis (RA) refractory to methotrexate. METHODS: In this randomized, open
      label, 3-stage design, 43 subjects were enrolled in 7 dose groups. In Stage I, 15
      subjects received single SC doses of 0.5, 1.5, or 3.0 mg/kg. In Stage II, 21
      subjects received one of 3 regimens: 100 mg SC every 2 weeks (3 injections); 3
      mg/kg commercially-formulated IV infliximab every 2 weeks (2 infusions) followed
      by 100 mg SC every 2 weeks (3 injections); or 100 mg IM every 2 weeks (3
      injections). In Stage III, 7 subjects received 100 mg SC every 4 weeks (3
      injections). RESULTS: No treatment-related serious adverse events were observed,
      and there were no serious injection site reactions. A low-titer infliximab
      antibody response was detected in 27% of subjects receiving single SC doses, 5%
      receiving multiple SC doses, and 43% receiving IM doses. SC administration
      yielded roughly dose-proportional increases in Cmax and AUC. American College of
      Rheumatology 20% response (ACR20) was achieved 2 weeks after the last injection
      by 86.7% of subjects receiving single SC doses, 85.7% receiving SC doses every 2
      weeks, 85.7% receiving both IV and SC doses, 57.1% receiving multiple IM doses,
      and 80.0% receiving SC doses every 4 weeks. CONCLUSION: SC and IM treatment with
      this experimental infliximab formulation was well tolerated and was associated
      with a favorable ACR response.

PMID- 16583467
TI  - How meaningful is our evaluation of meaningful change in osteoarthritis?

PMID- 16583468
TI  - What are open-label extension studies for?

PMID- 16583469
TI  - Allogeneic bone marrow transplantation for autoimmune disease--the jury is still
      out.

PMID- 16583470
TI  - Paraarticular trabecular bone loss at the ultradistal radius and increased
      arterial stiffening in postmenopausal patients with rheumatoid arthritis.
AB  - OBJECTIVE: We recently reported enhanced arterial thickening in patients with
      rheumatoid arthritis (RA) and the importance of increased bone resorption in this
      process. Our aim was to examine whether arterial stiffening, another aspect of
      atherosclerosis, is also increased in patients with RA, and to determine if it is
      an important risk factor. METHODS: The subjects were 47 patients with RA and 49
      healthy controls, all postmenopausal women. Subjects having risk factors for
      atherosclerosis were excluded. Femoral-ankle (fa) pulse wave velocity (PWV) and
      brachial-ankle (ba) PWV were measured in all patients using a waveform analyzer.
      Bone mineral density (BMD) at the ultradistal radius was assessed by peripheral
      quantitative computed tomography. Inflammation markers (C-reactive protein,
      erythrocyte sedimentation rate, rheumatoid factor, platelet count) and bone
      resorption markers (urinary excretion of deoxypyridinoline and N-terminal
      telopeptide) were also measured. RESULTS: The median values of faPWV and baPWV in
      RA patients were 1124 cm/s [interquartile range (IQR) 1040-1175] and 1539 cm/s
      (IQR 1297-1738), respectively, which were significantly greater than the
      respective values of 982 cm/s (IQR 819-1054; p < 0.001) and 1322 cm/s (IQR 1112
      1398; p = 0.004) in controls. In multiple regression analysis, the presence of RA
      emerged as an independent factor associated with the greater faPWV and baPWV when
      adjusted for age, blood pressure, and smoking. In RA patients alone, BMD in the
      trabecular bone component, but not for the total bone (cortical plus trabecular),
      at the ultradistal radius correlated significantly with both faPWV and baPWV.
      Multiple regression analysis showed that trabecular BMD at the distal radius was
      a significant factor independently associated with greater faPWV and baPWV when
      adjusted for age, blood pressure, and smoking. None of the measured inflammation
      markers or bone resorption markers correlated with either faPWV or baPWV in
      patients with RA. CONCLUSION: Patients with RA show increased arterial
      stiffening, in addition to the arterial thickening we have previously reported,
      supporting the notion of enhanced atherosclerosis in RA patients. Paraarticular
      bone loss in the trabecular bone component at the ultradistal radius is a factor
      significantly associated with increased arterial stiffening in RA patients.

PMID- 16583471
TI  - Prevalence and clinico-serological correlations of anti-alpha-enolase, anti-C1q,
      and anti-dsDNA antibodies in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the prevalence and clinico-serological correlations of
      anti-enolase, anti-C1q, and anti-dsDNA antibodies in patients with systemic lupus
      erythematosus (SLE). METHODS: Sixty-eight sera randomly obtained from SLE
      patients were examined. Anti-alpha-enolase antibodies were detected by immunoblot
      on recombinant protein; anti-C1q and anti-dsDNA antibodies were detected using an
      ELISA. RESULTS: Anti-alpha-enolase, anti-C1q, and anti-dsDNA antibodies were
      positive in 21%, 62%, and 63% of patients, respectively. A correlation was found
      between anti-dsDNA and anti-C1q antibodies, while anti-enolase antibodies did not
      correlate with the other 2 specificities. Anti-alpha-enolase antibodies were not
      correlated with any of the clinical and serological variables examined. Anti-C1q
      antibodies were correlated with ECLAM score, leukopenia, complement levels, and
      active renal involvement. Anti-dsDNA antibodies correlated with arthritis,
      leukopenia, complement levels, and the presence of renal involvement, independent
      of activity. In patients with active renal disease anti-dsDNA antibodies were
      correlated with a poor renal outcome, occurring after a mean period of 24 months.
      CONCLUSION: These data suggest the association of anti-C1q antibodies with
      disease flares and active renal disease in SLE. The observed association of anti
      dsDNA antibodies and renal disease was expected. Further analysis is required to
      fully assess the clinical significance of anti-a-enolase antibodies.

PMID- 16583472
TI  - Angiotensin-converting enzyme insertion/deletion polymorphism and systemic lupus
      erythematosus: a metaanalysis.
AB  - OBJECTIVE: To explore whether insertion (I) and deletion (D) polymorphisms within
      intron 16 of the angiotensin-converting enzyme (ACE) gene confer susceptibility
      to systemic lupus erythematosus (SLE) and lupus nephritis (LN). METHODS: We
      surveyed studies of ACE I/D polymorphism and SLE using Medline and manual
      searches. We conducted a metaanalysis of the DD genotype (recessive effect), DD
      and DI genotype (dominant effect), and D allele of the ACE overall and in each
      ethnic population. We performed a metaanalysis of ACE I/D polymorphism in SLE and
      LN. RESULTS: Thirteen comparison studies were included in our metaanalysis
      consisting of 1411 patients with SLE and 1551 controls. We found no association
      of ACE I/D polymorphism with SLE in the total sample and by ethnic groups. There
      was a trend for association of the DD genotype (OR 1.212, 95% CI 0.966-1.520, p =
      0.097) and the D allele with SLE in Caucasian patients (OR 1.157, 95% CI 0.991
      1.349, p = 0.064); however, this was not statistically significant. The
      metaanalysis also showed no association of the ACE I/D polymorphisms with LN.
      CONCLUSION: This metaanalysis of 2962 subjects showed there is a lack of
      association of the ACE I/D polymorphism with SLE and LN.

PMID- 16583473
TI  - Relationship between interleukin 6 promoter polymorphism at position -174, IL-6
      serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica.
AB  - OBJECTIVE: To assess the role of -174 G/C promoter polymorphism of interleukin 6
      (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also
      investigated whether this polymorphism modulates the circulating level of IL-6
      and the risk of relapse/recurrence in a series of patients with PMR followed up
      prospectively. METHODS: A prospective study of 112 consecutive, untreated
      patients with isolated PMR (i.e., without evidence of giant cell arteritis) who
      were followed up for at least 24 months. This cohort represented all patients
      diagnosed over a 5-year period in one Italian rheumatological secondary referral
      center. Patients were monitored for clinical signs/symptoms and acute-phase
      reactants. All PMR patients and 112 population-based controls from the same
      geographic area were genotyped for IL-6 polymorphism at position -174 by
      molecular methods. IL-6 serum levels were measured in 67 PMR patients and 43
      population-based controls. RESULTS: The distribution of the G/C 174 genotype was
      similar in PMR patients and controls. No significant associations with IL-6
      promoter polymorphism at position -174 were found when PMR patients with and
      without relapse/recurrence were compared. Controls homozygous for the C allele
      had higher serum IL-6 levels than the carriers of the G allele (4.5 +/- 3.7 pg/ml
      vs 1.8 +/- 2.1 pg/ml, p = 0.01). Patients homozygous for the allele C had
      significantly higher values of IL-6 during followup than patients carrying GC or
      GG genotypes. CC homozygosity was significantly more frequent in patients with
      persistently elevated levels of IL-6 than in those without. The presence of
      persistently elevated IL-6 levels, but not the CC genotype, was associated with
      an increased frequency of relapse/recurrence. CONCLUSION: Our findings show that
      the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to
      PMR. However, CC genotype characterized PMR patients with persistently elevated
      levels of IL-6 who are at higher risk of developing relapse/recurrence. A
      genetically modulated pattern of IL-6 production could affect the longterm
      outcome of patients with PMR.

PMID- 16583474
TI  - Myelopathies secondary to Sjogren's syndrome: treatment with monthly intravenous
      cyclophosphamide associated with corticosteroids.
AB  - OBJECTIVE: Central nervous system manifestations in Sjogren's syndrome (SS)
      include focal deficits, optic neuritis, and myelopathies. Acute and chronic
      myelopathies are frequently severe and sometimes respond poorly to
      corticosteroids. The efficacy of intravenous (IV) cyclophosphamide (CYC) has been
      suggested in single case reports. METHODS: We describe the potential usefulness
      of IV CYC in SS patients with severe myelopathies. Fourteen patients [with acute
      (n = 6) and chronic (n = 8) myelopathies] were treated with monthly CYC infusions
      (700 mg/m2) in addition to 500 mg of corticosteroids for one year. We evaluated
      the disability before and after CYC treatment using a walking distance
      calculation and the Expanded Disability Status Scale (EDSS). RESULTS: CYC
      treatment was well tolerated in all cases without serious adverse events. Nine
      patients (including the 6 with acute myelopathy) were improved after CYC
      treatment. Three patients were stabilized and 2 patients with chronic
      myelopathies had moderate progression of disability. The mean walking distance
      increased from 48.2 m before to 180.4 m after CYC treatment (p < 0.02). Mean EDSS
      score decreased from 6.6 to 5.7 (not significant). We found a correlation between
      the length of time before CYC treatment and clinical improvement for both the
      walking distance (p < 0.02) and the EDSS score (p < 0.05). CONCLUSION: Although a
      randomized multicenter controlled study is warranted to confirm our findings, IV
      CYC infusions seem to be useful for the treatment of myelopathies secondary to
      SS, particularly in acute but also in progressive cases. This treatment should be
      strongly considered as soon as possible when disease progression is observed.

PMID- 16583475
TI  - Is sulfasalazine effective in ankylosing spondylitis? A systematic review of
      randomized controlled trials.
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of sulfasalazine (SSZ) for the
      treatment of ankylosing spondylitis (AS). METHODS: We searched randomized and
      quasi-randomized trials in any language comparing SSZ with placebo in treatment
      of AS. Two reviewers independently selected the studies and assessed the
      methodological quality. Data were extracted from the chosen studies and
      metaanalysis was conducted with RevMan software. RESULTS: We identified 11
      trials, in which a total of 895 patients were treated for periods ranging from 12
      weeks to 3 years. The pooled analysis showed that differences between SSZ and
      placebo were statistically significant only in erythrocyte sedimentation rate
      (ESR) and the severity of spinal stiffness, favoring SSZ over placebo. Weighted
      mean differences were ESR -4.79 mm/h (95% CI -8.80 to -0.78) and spine stiffness 
      13.89 mm (95% CI -22.54 to -5.24) on 100 mm visual analog scale (where 0 = no
      stiffness, 100 = severe stiffness). Nissila 1988 is the only trial in which SSZ
      showed benefit in primary outcome analyses, including back pain, chest expansion,
      occiput-to-wall test, and patient's general well-being. Compared with other
      trials, patients in this trial had the shortest disease duration and highest
      level of baseline ESR, and it had the greatest proportion of patients with
      peripheral arthritis. Significantly more withdrawals for side effects (relative
      risk 1.47, 95% CI 1.01 to 2.13) were found in the SSZ than in the placebo group,
      although severe side effects were rare. CONCLUSION: Across all patients with AS,
      SSZ showed some benefit in reducing ESR and easing spinal stiffness, but no
      evidence of benefit in physical function, pain, spinal mobility, enthesitis, or
      patient and physician global assessment. Patients at an early stage of disease,
      with higher level of ESR (or active disease) and peripheral arthritis, might
      benefit from SSZ.

PMID- 16583476
TI  - The cost-effectiveness of infliximab (Remicade) in the treatment of ankylosing
      spondylitis in Canada.
AB  - OBJECTIVE: To estimate the cost-effectiveness of the treatment of ankylosing
      spondylitis (AS) with infliximab (Remicade) in Canada over the long term, with
      both international and Canadian treatment regimens. METHODS: A previously
      published disease model based on functional capacity and disease activity was
      adapted to the Canadian setting. Current resource consumption from a cross
      sectional bottom-up burden-of-illness study in 545 patients at different levels
      of severity of AS in 4 Canadian provinces was incorporated into the model. Cost
      effectiveness estimates were based on a 3-month placebo-controlled clinical trial
      with 2-year open extension as well as a 4-year followup study of clinical
      practice in Canada. In the cost-effectiveness model, patients with insufficient
      response to treatment at 12 weeks (> or = 50% reduction in Bath Ankylosing
      Spondylitis Disease Activity Index) discontinue treatment. In view of the long
      disease duration, simulations over a 30-year timeframe were performed,
      incorporating disease progression from cohort studies and assumptions about
      treatment continuation beyond the clinical trial from the trial extension period.
      Results are presented in Canadian dollars, from the societal and healthcare payer
      perspectives, with both costs and effects discounted at 5%. RESULTS: Over a 30
      year timeframe, with the assumption that patients' disease would remain stable
      while on treatment, the cost per quality-adjusted life-year (QALY) gained in the
      societal perspective is $37,491, using the treatment regimen in the clinical
      trial (5 mg/kg every 6 weeks). Using the dosing regimen of the Canadian study
      (75% at 3 mg/kg every 8 weeks, 15% at 3 mg/kg every 6 weeks, and 10% at 5 mg/kg
      every 8 weeks) the cost per QALY is dollar 10,264. Assuming that patients on
      treatment progress at half the rate of untreated patients, the cost-effectiveness
      ratios are dollar 45,121 and dollar 13,883, respectively, while the most
      conservative assumption that progression is the same in both arms, the ratios are
      dollar 54,137 and dollar 18,712, respectively. The results are sensitive to the
      dosing regimen adopted, the discontinuation rate, and assumptions concerning
      disease progression while on treatment. CONCLUSION: Our results indicate that
      infliximab therapy for patients with active AS would be cost-effective (ranges
      dollar 10,264-dollar 54,137 per QALY) in a Canadian setting.

PMID- 16583477
TI  - HFE gene mutations are associated with osteoarthritis in the index or middle
      finger metacarpophalangeal joints.
AB  - OBJECTIVE: . To test the hypothesis that possession of either C282Y or H63D
      mutations in the HFE gene is associated with primary osteoarthritis (OA) in
      joints commonly affected in hemochromatotic arthropathy. METHODS: HFE genotyping
      was performed in 87 patients with radiologically proven OA in 3 joint regions:
      index or middle finger metacarpophalangeal joints (MCP2,3; n = 52), elbow joints
      (n = 8), ankle, intertarsal or tarsometatarsal joints (ankle/IT/TMT; n = 27); and
      in 56 patients with radiologically proven OA in finger interphalangeal (IP)
      joints, but not MCP2,3 joints (IP OA control group). HFE mutation frequencies in
      these groups were also compared to those in a similar population (Busselton
      population control group). RESULTS: A statistically significant association
      between HFE mutations and OA was observed for the MCP2,3 joints (p = 0.0001) and
      the ankle/IT/TMT joint group (p = 0.002) as well as for the 3 joint regions
      collectively (p = 0.0001), but not for the elbow joints (p = 0.062). Comparison
      with the Busselton population controls showed similar statistically significant
      associations, except for the elbow and ankle/IT/TMT groups, where similar trends
      were observed. CONCLUSION: HFE gene mutations are associated with OA in the
      MCP2,3 joints. These mutations may be markers for a polyarticular OA phenotype.

PMID- 16583478
TI  - Do exercise and self-management interventions benefit patients with
      osteoarthritis of the knee? A metaanalytic review.
AB  - OBJECTIVE: Osteoarthritis (OA) is the most prevalent health condition among
      seniors and it causes significant pain and disability. We assessed the influence
      of patient education and exercise regimens on the well-being of patients with
      knee OA. METHODS: A metaanalysis was conducted on 16 studies reporting exercise
      and/or self-management interventions for patients with knee OA. The effects on
      physical and psychological well-being were assessed immediately after the
      interventions. RESULTS: Compared to control conditions, exercise regimens led to
      improvement in physical health (by self-report and direct measures) and in
      overall impact of OA. Perceived psychological health remained unchanged by the
      exercise programs. Although the effect sizes for the self-management programs
      were significant for psychological outcomes and for the overall effect of OA,
      there was a significant difference between self-management and control groups
      only in psychological outcomes. CONCLUSION: Overall, both patient education and
      exercise regimens had a modest, yet clinically important, influence on patients'
      well-being.

PMID- 16583479
TI  - Measuring the outcome of health resort programs.
AB  - OBJECTIVE: To evaluate the metric properties and practicability of valid,
      internationally available outcome instruments in the special setting of health
      resort programs. METHODS: A cohort study in a convenience sample of patients with
      low back pain, upper back pain, conditions of the lower extremities, and
      conditions of the upper extremities was conducted. Their functioning and health
      were assessed before and after a health resort program by the disease-specific
      North American Spine Society (NASS) instruments Lumbar NASS and Cervical NASS;
      WOMAC Osteoarthritis Index; Disabilities of Arm, Shoulder and Hand Questionnaire;
      and the general instrument, Medical Outcome Study Short Form-36 (SF-36). RESULTS:
      Completeness on the scale level ranged between 1% and 10%. Criterion validity of
      condition-specific instruments was confirmed by stronger associations of the pain
      and function scales to the Physical Health component of the SF-36 (r = -0.59 to 
      0.79, p < 0.001 for all scales) than to the Mental Health component (r = -0.11,
      NS, to r = -0.42, p < 0.001). Reliability (Cronbach's alpha coefficient) was
      higher than 0.8 for all scales of condition-specific instruments and for 6 of 8
      SF-36 scales. Floor and ceiling effects ranged between 0% and 7%. The condition
      specific instruments demonstrated a good responsiveness with an effect size
      ranging between 0.28 and 0.55 and with a standardized response mean between 0.32
      and 0.94. The responsiveness of most SF-36 scales was similar, but the Physical
      Function scale showed a lower responsiveness than the condition-specific scales.
      CONCLUSION: The evaluated instruments can be recommended for use in clinical
      trials that assess the outcome of health resort programs.

PMID- 16583480
TI  - Increased expression of N-methyl-D-aspartate receptor subunit 2D in the skin of
      patients with fibromyalgia.
AB  - OBJECTIVE: We studied the expression of N-methyl-D-aspartate receptors (NMDAR) in
      skin of patients with fibromyalgia (FM) to investigate their role. METHODS: The
      presence of NMDAR subtype 2B (NR2B) and subtype 2D (NR2D) was examined in skin
      tissues by immunohistochemistry and immunoblot. Skin tissues from 11 female
      patients with FM were examined and compared to those of 8 age- and sex-matched
      healthy controls. RESULTS: NR2D expression was increased in the skin of patients
      with FM versus controls. There was no difference in the expression of NR2B
      between FM patients and controls. CONCLUSION: The increased expression of NMDAR
      found in FM skin could be indicative of a more generalized increase in other
      peripheral nerves. This suggests that NR2D-selective antagonists may have
      implications in the treatment of allodynia in patients with FM.

PMID- 16583481
TI  - Corticosteroid treatment of refractory Kawasaki disease.
AB  - OBJECTIVE: To review the indications for corticosteroids in patients with
      Kawasaki disease (KD) treated by pediatric rheumatologists in Canada and to
      determine their efficacy on fever in patients with refractory KD. METHODS: All
      practicing pediatric rheumatologists in Canada identified KD patients treated
      with corticosteroids and completed a standard data form that included
      demographics, clinical and laboratory features, imaging studies, and therapeutic
      interventions, by chart review. RESULTS: Thirty-two patients with KD (14 female;
      18 male: mean age 4.6 years) were treated with corticosteroids. Corticosteroids
      were used in 26 patients (81%) for persistent fever despite treatment with
      intravenous immunoglobulin (IVIG) (refractory KD), 5 patients (19%) for
      congestive heart failure, and 1 patient for persistent acute phase symptoms other
      than fever. The 26 patients with refractory KD are the primary subject of this
      report. Twenty-two patients (85%) had rapid, sustained resolution of fever after
      corticosteroids. There were no serious reported adverse effects. Eight patients
      (31%) treated with corticosteroids developed coronary artery (CA) aneurysms and 9
      (35%) developed CA dilatations without aneurysms. Of those who developed CA
      aneurysm, 4 had aneurysms detected prior to IV methylprednisolone (MP) on
      echocardiograms performed on days 6-27 (mean day 13) of illness. The remaining 4
      patients had CA aneurysm detected after IVMP therapy, on echocardiograms
      performed on days 13-49 (mean day 23) of illness, 1-25 days (mean 9 days) after
      IVMP. In patients with one year or more of followup, 46% had resolution of CA
      abnormalities. CONCLUSION: Corticosteroids are effective in the treatment of
      fever in most patients with IVIG-refractory KD. A multicenter prospective study
      is needed to determine the effect of corticosteroids on CA outcome in patients
      with refractory KD.

PMID- 16583482
TI  - Recurrent transient synovitis of the hip in childhood. Longterm outcome among 39
      patients.
AB  - OBJECTIVE: To describe the outcome of children with recurrent transient synovitis
      (TS) of the hip. METHODS: A retrospective chart review of children with at least
      2 separate episodes of TS between 1986 and 2003. We described the diagnostic
      investigations and outcome of these patients. A followup telephone survey for
      disability and pain scores was performed in 2004. RESULTS: We studied 39
      children, 26 boys and 13 girls, from 6 pediatric rheumatology centers. The mean
      age at initial episode was 6 +/- 2.6 years. There were a total of 102 episodes
      (mean 2.9 +/- 1.6, median 2, range 2-10). All but 2 children had normal plain
      radiographs of the hip. All patients were contacted 4.2 +/- 2.5 years after the
      first episode. None developed clinical Perthes disease or other chronic
      orthopedic condition. Three (8%) patients developed chronic disease: one had
      familial Mediterranean fever and 2 developed spondyloarthropathies, 0.5, 2, and 6
      years after presentation. At followup 26 of 36 patients were asymptomatic, and 10
      reported rare hip pain after intensive physical effort. CONCLUSION: Children with
      recurrent TS usually have a benign course. In some patients recurrent TS may be
      the presenting feature of a chronic inflammatory condition. No progression to
      chronic orthopedic conditions was observed.

PMID- 16583483
TI  - Twenty-year remission of rheumatoid arthritis in 2 patients after allogeneic bone
      marrow transplant.
AB  - We describe 21 and 19 year followup of 2 patients with severe rheumatoid
      arthritis (RA) who in 1984 and 1986 underwent allogeneic bone marrow
      transplantation (BMT) after full myeloablative conditioning, for therapy-induced
      aplastic anemia. Regarding the arthritis, both patients are well, taking no
      medications, and free of signs or symptoms of active RA. One patient is in
      excellent health overall, while the other has coronary artery disease and chronic
      obstructive pulmonary disease attributable to smoking. We suggest that allogeneic
      BMT may be a curative treatment for severe RA.

PMID- 16583484
TI  - Mycobacterium marinum arthritis mimicking rheumatoid arthritis.
AB  - Mycobacterium marinum is an atypical mycobacterium found in salt and fresh water.
      M. marinum infection occurs following skin trauma in fresh or salt water and
      usually presents as a localized granuloma or sporotrichotic lymphangitis. It
      rarely affects the musculoskeletal system. We describe a patient who presented
      with subcutaneous nodules and an inflammatory arthritis that was thought to be
      rheumatoid arthritis, and was treated as such with corticosteroids, methotrexate,
      and anti-tumor necrosis factor-alpha therapy, with worsening of his arthritis.

PMID- 16583485
TI  - Intrathoracic arteritis: a paraneoplastic presentation of malignant melanoma.

PMID- 16583486
TI  - Chronic infantile neurological cutaneous and articular syndrome--an early
      description.

PMID- 16583490
TI  - Hypothyroidism contributes to increased triglyceride levels among patients with
      systemic sclerosis.

PMID- 16583487
TI  - Septic abscess in a child with juvenile idiopathic arthritis receiving anti-tumor
      necrosis factor-alpha.

PMID- 16583491
TI  - Fibromyalgia is a neuropathic pain syndrome.

PMID- 16583492
TI  - Milk's fatty acid may help control RA.

PMID- 16583493
TI  - Botox for tennis elbow.

PMID- 16583494
TI  - Dry eyes? Eat more fish.

PMID- 16583495
TI  - Upset can spark injury.

PMID- 16583496
TI  - Quick test for recurrent bladder cancer.

PMID- 16583497
TI  - Aging and attitude.

PMID- 16583498
TI  - I've read that hyaluronic acid knee injections can be used to postpone knee
      surgery. Can hyaluronic acid in pill form provide the same relief?

PMID- 16583499
TI  - I have an artificial heart valve and am on warfarin for life. I would like to be
      able to test my own clotting at home. I have heard that there are test devices
      for this, as there are for diabetics. Why don't more warfarin patients know about
      them?

PMID- 16583500
TI  - Comparative crystallographic and hydrogen-bonding analysis of cholestane
      derivatives.
AB  - A crystallographic comparison of some geometrical and structural features for a
      series of steroids (cholestane derivatives) is made in the present paper.
      Selected bond distances and bond angles of interest are discussed in detail.
      Conformations of individual ring systems in a series of 28 cholestane derivatives
      are calculated and discussed. Graphical presentations of ring conformations are
      made for all the five- and six-membered rings to show the frequency of their
      occurrence. X--H...A intra- and intermolecular interactions in the identified
      molecules are discussed with the standard distance and angle cut-off criteria.
      Distance-angle scatter plots for both kinds of interactions are presented for
      better understanding of packing interactions existing in cholestane molecules.

PMID- 16583501
TI  - Better image-guided surgery.

PMID- 16583502
TI  - HIV drug resistance and you. Resistance overview. A look at the basics.

PMID- 16583503
TI  - Scientists plan field tests for GM mosquitoes.

PMID- 16583504
TI  - The P&T Society.

PMID- 16583505
TI  - Did welfare reform influence the fertility of young teens?
AB  - During the 1990s, states made several reforms to their welfare programs designed
      to reduce teenage fertility among minors. Among the most prominent of these
      changes, states started requiring teenage mothers younger than 18 to live with a
      parent or legal guardian and enroll in high school in order to receive welfare
      benefits. Using natality data from the National Center for Health Statistics, we
      compare the trend in fertility rates for young women aged 15 to 17 to the trend
      for a control group of 18-year-olds. Our estimates imply that the annual percent
      decline in fertility rates following implementation of these minor parent
      provisions was 0.7 percentage points larger for young teens than for teens aged
      18, a difference of over 22 percent.

PMID- 16583510
TI  - Food news blues.

PMID- 16583511
TI  - The philanthropy of sweat.

PMID- 16583512
TI  - Minnesota answers the call. Jim Van Vooren, M. D.

PMID- 16583513
TI  - Minnesota answers the call. Margy MacMillan, M. D.

PMID- 16583514
TI  - Minnesota answers the call. Kunal Jani.

PMID- 16583515
TI  - Minnesota answers the call. Sigrid Bachmann, M. D.

PMID- 16583516
TI  - Minnesota answers the call. John A. Ness, M. D.

PMID- 16583517
TI  - Minnesota answers the call. Clifford Phibbs Jr., M. D.

PMID- 16583518
TI  - Minnesota answers the call. Vincent Ohaju, D.O.

PMID- 16583519
TI  - Minnesota answers the call. Sandra Hanson, M. D.

PMID- 16583520
TI  - The land you will find.

PMID- 16583521
TI  - A challenge to improve quality of care.

PMID- 16583522
TI  - Minnesota answers the call.

PMID- 16583523
TI  - Less is more.

PMID- 16583524
TI  - Five fixes to improve drug safety. Ideas for how to prevent another Vioxx
      debacle.

PMID- 16583525
TI  - Service delivery innovations at Mayo Clinic.
AB  - Mayo Clinic has a long-standing reputation as a leader in the basic and clinical
      sciences. However, there is little in the published literature about Mayo
      Clinic's contributions to the delivery of health care services. This article is
      an overview of what Mayo brought to health care delivery between the 1860s and
      the 1980s, highlighting some of the lesser-known innovations that have influenced
      health care delivery on a national and international level such as the
      development of group practice and medical specialties, the creation of medical
      records, the use of allied health care providers, and facility design.

PMID- 16583526
TI  - Smoking rates among American Indian women giving birth in Minnesota. A call to
      action.
AB  - Maternal smoking is associated with a number of adverse effects including
      neonatal mortality, preterm delivery, low birth weight, decreased lung growth and
      function, and increased incidence of lower respiratory infections. This study
      looked at smoking trends among American Indian and white women in Minnesota who
      gave birth between 1999 and 2003. The authors used data from birth certificates
      issued by the state to determine the rate of smoking among both groups of women.
      They broke down the data further to look at and compare smoking rates of American
      Indian and white women based on where they gave birth (greater Minnesota or the
      Twin Cities metro area), when they began receiving prenatal care, their level of
      education, their age, the number of children they already had, and the weight of
      their baby. They found that 39% of American Indian women in Minnesota who gave
      birth during that period reported smoking, compared with 11% of white women. In
      addition, their findings showed that cigarette use among American Indian women in
      Minnesota who gave birth in 2003, was 36.5%--double the national rate of 18.3%
      forAmerican Indian women.

PMID- 16583527
TI  - The power of nursing: can it ever be mobilized?

PMID- 16583528
TI  - From process to product.

PMID- 16583529
TI  - 'My mother's leaving today?': A pilot study on awareness of discharge date in the
      chronically critically ill.

PMID- 16583530
TI  - HIV and hyperlipidemia: current recommendations and treatment.
AB  - In recent years, CVD risk factors have been recognized among individuals living
      with HIV/AIDS (Dube et al., 2003) and have been associated with the medication
      regimen (HAART) used to manage the diseases. A specific class of HIV medication,
      protease inhibitors, has been implicated in elevating serum levels of
      triglyceride and cholesterol in treated individuals (Green, 2002; Penzak & Chuck,
      2000). However, current treatments for hyperlipidemia in HIV are not always
      effective and can be dose-limited due to interactions with HAART regimens
      (Currier, 2002). Dietary guidelines by the NCEP have been recommended as the
      first-line approach to managing this condition. Well-controlled studies are
      needed to test the effectiveness of the NCEP diet on HIV-positive individuals.
      Published studies have focused primarily on dietary counseling and have lacked
      randomization, control groups, and adequate description of the counseling
      intervention. Because the mechanism associated with dyslipidemia and HAART is not
      fully understood, rigorously controlled dietary studies may provide the
      opportunity to investigate how diet metabolically affects lipid levels during
      HAART treatment.

PMID- 16583531
TI  - Developing a comprehensive bariatric protocol: a template for improving patient
      care.

PMID- 16583532
TI  - Improved symptom management through enrollment in an outpatient congestive heart
      failure clinic.

PMID- 16583533
TI  - Patient decision making concerning clinical trials.

PMID- 16583534
TI  - Review of chest tube use.

PMID- 16583535
TI  - Resistant 'superbugs' create need for novel antibiotics.

PMID- 16583536
TI  - [Information technology should make health care safer and better. But there is
      still a long way to go].

PMID- 16583537
TI  - [Overweight, obesity...and BMI. The INTERHEART study shows that the BMI should
      probably be abolished--the waist-hip ratio is better].

PMID- 16583538
TI  - [Testosterone valuable for women--deficiency might require substitution. The
      significance for sexuality, metabolism and mental well-being].

PMID- 16583539
TI  - [Hematopoietic stem cell transplantation in MS. Justified, and if so, when?].

PMID- 16583540
TI  - [Hand tendon injuries].

PMID- 16583541
TI  - [A new program for better clinical supervision of students. A joint project at
      the Halsouniversitet and county council in Ostergotland].

PMID- 16583542
TI  - [An unusual type of hemolysis in Tarui disease in two families originated in the
      county of Vasterbotten].

PMID- 16583543
TI  - [Systemic steroid therapy in allergic rhinitis].

PMID- 16583544
TI  - [Time to abolish the sick building syndrome as a clinical diagnosis].

PMID- 16583545
TI  - [Drug development costs are overstated by the industry].

PMID- 16583547
TI  - [100 percent satisfied patients?].

PMID- 16583546
TI  - [Turn the negative spiral of psychiatry around--give younger physicians
      leadership responsibility].

PMID- 16583548
TI  - [The revised allergy terminology can also increase misunderstanding].

PMID- 16583549
TI  - [Penicillin V treatment in erythema migrans can give a false security].

PMID- 16583550
TI  - [Swedish confusion about generic preparations].

PMID- 16583551
TI  - Usage and data collection patterns for a novel web-based foodborne-disease
      surveillance system.
AB  - This paper discusses the traditional system of foodborne-illness surveillance and
      provides a justification for increased syndromic surveillance of foodborne
      illness. A new Internet-based method for reporting foodborne disease is
      explained, and data entered by 7,500 visitors to the pilot Web site are described
      with respect to completeness and basic demographic factors. Data entry patterns
      show that visitors are willing to report a suspected case of foodborne illness
      online and do so in greater detail than is commonly obtained from traditional
      reports made over the telephone.

PMID- 16583552
TI  - Assessing occupational mercury exposures during the on-site processing of spent
      fluorescent lamps.
AB  - On-site processing of spent fluorescent lamps reduces storage space requirements
      and prevents mercury-containing lamp contents from entering the municipal waste
      stream, but such processing activities are typically not carried out in
      facilities specifically designed for the operation. This circumstance is of
      particular concern because lamp-handling and -crushing operations can release
      mercury vapors and aerosols that constitute an occupational exposure risk. In the
      study reported here, sampling for airborne mercury was performed during the
      processing of fluorescent lamps in an enclosed work area and in an open, outdoor
      work environment. In both enclosed and open work environments, exposures in
      excess of the established mercury exposure limit were detected. Simple
      interventions to prevent this possible unanticipated source of mercury exposure
      are described.

PMID- 16583553
TI  - Waste disposal in first-nations communities: the issues and steps toward the
      future.
AB  - The interests of First Nations communities in Canada have traditionally had
      little voice at the various points of authority that maintain the equilibrium or
      balance necessary to get environmental protection laws ratified, regulations
      distributed, and enforcement actions initiated on First Nations lands. (First
      Nations is the term commonly used in Canada to describe the various societies of
      indigenous peoples who are accorded status as "Indians" by the Indian Act of 1985
      and who are not of Inuit or Metis descent.) Along with a lack of adequate funding
      to address human and environmental issues-as well as past industrial exploitation
      of First Nations lands-the safety and acceptability of many solid waste
      management practices in Canadian First Nations communities have become a serious
      concern for many members from both human and environmental health perspectives. A
      history of poor management, monitoring, and remediation of solid waste facilities
      across Canada's First Nations Communities and the lack of current resolve over
      this issue has left First Nations people feeling the consequences of pollution to
      their environment: rivers, land, and air. First Nations people are traditionally
      connected to the land, and consequently the degradation of the environment also
      leads to a decline in a way of life for the people and thus a decline in the
      cultural health of communities. This article examines the issues surrounding
      waste management on First Nations communities, looks at how First Nations are
      trying to handle their solid waste, and considers the larger issues of
      environmental degradation that First Nations communities face throughout Canada.

PMID- 16583554
TI  - Developing environmental public health leadership.

PMID- 16583555
TI  - Leadership opportunities in environmental public health.

PMID- 16583556
TI  - Innovation is a necessary component of environmental health.

PMID- 16583557
TI  - Public access and getting the message out.

PMID- 16583558
TI  - From the invisible profession to a profession of truth.

PMID- 16583559
TI  - [Genetically modified peas in discussion].

PMID- 16583560
TI  - [Inhibition of virulence factors. A new approach to antibiotic development].

PMID- 16583561
TI  - [How does paracetamol work? A wider mosaic of action mechanisms].

PMID- 16583562
TI  - [New hope for the cancer patient?].

PMID- 16583563
TI  - [Clinical proof is the decisive terrain. The history of alkylating agents].

PMID- 16583564
TI  - [Platinum complexes in cancer pharmacy. Individual patient cytostatic
      preparation].

PMID- 16583565
TI  - [Development, importance and perspectives. Tumor inhibiting metal compounds].

PMID- 16583566
TI  - [Special qualities of inorganic cytostatics. Medicinal chemistry of platinum
      complexes].

PMID- 16583567
TI  - [Overview of development status and clinical action. Cisplatin and its
      analogues].

PMID- 16583568
TI  - [The patient in the center. Pharmaceutical care of cancer patients].

PMID- 16583569
TI  - [Individualized dosage of cytostatics. Dose individualization in cancer
      chemotherapy].

PMID- 16583570
TI  - [Perfect drug targeting. Glufosfamide a new derivative].

PMID- 16583571
TI  - [International Dictyostelium Conference 2005].

PMID- 16583572
TI  - [The utility of antilipemic agents in the area of secondary prevention].

PMID- 16583573
TI  - Development of Postpartum Depression Screening Scale (PDSS): a Thai version for
      screening postpartum depression.
AB  - To validate a Postpartum Depression Screening Scale (PDSS) for screening
      postpartum depressive disorder in Songkhla Thai population, a screening test was
      conducted. A Thai version of the PDSS was developed using back translation and
      pre-tested on a prospective cohort of 400 postpartum women at 6-8 weeks from
      November 2003 to September 2004 in a university hospital, Southern Thailand. The
      diagnosis of postpartum depression was determined using DSM-IV diagnostic
      criteria for minor and major depressive disorders. The alpha reliability for the
      total PDSS was 0.9. The recommended cut-off scores of 51for screening major or
      minor depressive disorders and of 90 for screening major depressive disorder Area
      under the receiver operating characteristics (ROC) curve was 0.8 for major and
      minor depressive disorders and 0.9 for major depressive disorder In conclusion,
      this is a useful and beneficial instrument as there is no other Thai version
      validated instrument for postpartum depression.

PMID- 16583574
TI  - Result of ambulatory diet therapy in gestational diabetes mellitus.
AB  - OBJECTIVES: To evaluate the effectiveness of an ambulatory program for glycemic
      control of women with gestational diabetes mellitus (GDM). MATERIAL AND METHOD: A
      total of 33 women with GDM whose FBS from OGTT > or = 105 mg/dl were scheduled to
      attend weekly ambulatory care for dietary therapy with their family. FBS and 2
      hour postprandial blood glucose were monitored every visit for a few weeks. At
      the end of this program, those with poor glycemic control were admitted for
      further tight dietary control by conventional 3-day course after which insulin
      was finally started for the women whose glycemic control remained poor. RESULTS:
      After the ambulatory program, 14 of 33 cases (42.4%) achieved good glycemic
      control without hospitalization. Another 6 cases (18.2%) did not need insulin
      therapy after admission for 3-day intensive dietary therapy. Altogether, 20 out
      of 33 cases (60.6%) of GDM whose FBS from OGTT > or = 105 mg/dl could avoid
      insulin therapy after attending the ambulatory program alone or with additional 3
      day intensive dietary therapy course. Similar effectiveness was observed from the
      authors' previous study on 3-day intensive dietary therapy alone. CONCLUSION: The
      authors' current ambulatory dietary therapy program has shown to be effective in
      achieving good glycemic control and avoiding unnecessary insulin therapy and
      admission in most cases of women with GDM. In the future, an even more effective
      ambulatory diet control may ascertain that once a woman is hospitalized, insulin
      should be started right away.

PMID- 16583575
TI  - Correlation of weight estimation in large and small fetuses with three
      dimensional ultrasonographic volume measurements of the fetal upper-arm and
      thigh: A preliminary report.
AB  - OBJECTIVE: To determine the correlation of measuring fetal upper-arm and thigh
      volume using three-dimensional ultrasonography with weight estimation in large
      and small fetuses. MATERIAL AND METHOD: The authors included 46 pregnant women
      admitted for delivery in the Labor Room at Srinagarind Hospital, Khon Kaen
      University, between February 1 and September 30, 2004. Inclusion criteria were:
      1) singleton pregnancy; 2) delivery within 48 hours after study; 3) estimation
      birthweight < 2,500 g (small fetuses group: n = 22) or > 3,500 g (large fetus
      group: n = 24). All patients received two- and three-dimensional ultrasound
      examinations by an experienced practitioner The upper-arm and thigh volume were
      assessed using a three-dimensional ultrasound scanner. RESULTS: In the large
      fetus group, upper-arm and thigh volume measurements by three-dimensional
      ultrasound strongly correlated with birthweight, r = 0.805 (95%CI = 0.594-0.912)
      and r = 0. 739 (95%CI = 0.478-0.880), respectively. In the small fetuses group,
      the upper-arm and thigh volume measurements, by three-dimensional ultrasound,
      strongly correlated with birthweight, r = 0.868 (95%CI = 0.689-0.946) and r =
      0.835 (95%CI = 0.638-0.929), respectively. CONCLUSION: Upper-arm and thigh
      volumes measured by three-dimensional ultrasound highly correlates with weight
      estimation in large and small fetuses and can be used as a new modality for
      estimating fetal weight.

PMID- 16583576
TI  - Preoperative vaginal preparations for abdominal hysterectomy for the prevention
      of febrile morbidity: savlon douching vs povidone-iodine painting.
AB  - OBJECTIVE: To compare the effectiveness between savlon solution was douching and
      povidone-iodine solution painting for reducing febrile morbidity after total
      abdominal hysterectomy. STUDY DESIGN: Clinical trial. MATERIAL AND METHOD: One
      hundred and fifty patients at Srinagarind Hospital were scheduled for total
      abdominal hysterectomy (TAH). All subjects were non-randomly allocated to receive
      either savlon (1:1000 solutions) douching or povidone-iodine (1% solution)
      painting as pre-operative vaginal preparations. They also received Cefazolin 1
      gm. intravenously before the operation. The principal outcome of the study was
      febrile morbidity. RESULTS: The overall rate of febrile morbidity was 21 percent.
      The incidence of febrile morbidity in the savlon vs. povidone-iodine groups was
      16 (12/75) and 25 (19/75) percent, respectively. No statistically significant
      difference was found between the two groups (p-value = 0.16). The odds ratio was
      1.78 (95%CI 0.79 to 3.99) and adjusted odds ratio was 2.09(95%CI 0.86 to 5.10)
      CONCLUSION: The effectiveness between savlon solution douching and povidone
      iodine solution painting in conjunction with a prophylactic antibiotic before TAH
      for reducing febrile morbidity was not significant different.

PMID- 16583577
TI  - Mucinous carcinoma of the colon and rectum in Phramongkutklao Hospital.
AB  - OBJECTIVE: The objective of the present study was to compare the
      clinicopathological significance between mucinous carcinoma and nonmucinous
      adenocarcinoma. MATERIAL AND METHOD: Patients with carcinoma of the colon and
      rectum who had the first operation in the Department of Surgery, Phramongkutklao
      Hospital between 1999 and 2004 were included in the present study. Patients were
      divided into two groups: nonmucinous group and mucinous group.
      Clinicopathological data of these patients were recorded. RESULTS: Four hundred
      and nine patients were included in the present study. Forty four (10.7%) were
      mucinous carcinoma. There was no difference in sex distribution, location of
      tumors, depth of invasion, lymph node involvement, distant metastasis, TNM stage,
      lymphatic invasion, vascular invasion, perineural invasion, peritoneal seeding,
      curability, positive microscopic margin, and adhesion to the surrounding
      structure. CONCLUSION: Colorectal mucinous carcinoma had no clinicopathological
      difference from nonmucinous adenocarcinoma of colon and rectum.

PMID- 16583578
TI  - The optimal time for early excision in major burn injury.
AB  - INTRODUCTION: Early excision and grafting (E&G) drastically changed burn care in
      America by reducing morbidity, mortality and hospital length of stay (LOS). The
      present study was intended to determine whether an optimal time window exists
      between resuscitation and wound sepsis for the first E&G in a patient with a
      large burn. MATERIAL AND METHOD: The authors conducted a retrospective study of
      patients admitted between January 1994 and December 2000 with > or = 40% TBSA
      burns and at least 1 E&G procedure. Patients were grouped according to the day of
      their first operation. Patients allowed to heal indeterminate burns prior to
      excision and grafting of deep partial or full thickness burns were grouped as >
      or = d7 and were excluded from the present study. The authors correlated the time
      of first excision with infection, mortality and LOS. RESULTS: Seventy-five
      patients were identified and 12 patients allowed to heal indeterminate burn prior
      to excision and grafting of deep partial or full thickness burns were excluded.
      Sixty-three remaining patients included 51 males and 12 females. Mean burn size
      was 49% of total body surface area (TBSA) (44% deep partial or full thickness)
      and the mean age was 36 years. There were 61 flame (2 combined with electrical
      injuries), 1 scald and 1 chemical burn. Twelve died (19%) and 52 patients
      developed 121 infections. Whereas there was no statistical difference in
      mortality for patients operated on different days (p > 0.2), 60% of patients
      operated within the first 48 hours after injury died; this was not significant
      due to a small patient number CONCLUSIONS: The present data suggest that patients
      who undergo early excision and grafting within seven days following a major burn
      > or = 40% TBSA have equivalent infection or mortality rates regardless of when
      the first operation occurs between post burn day(PBD) 2 and PBD 7 (p > 0.2).

PMID- 16583579
TI  - Prevalence of prostate cancer in aging males receiving PSA (prostate specific
      antigen) screening test (A campaign for celebration of Siriraj Established Day).
AB  - Prostate cancer is a potential men's health problem. The prevalence of prostate
      cancer continues to rise. Serum PSA (Prostate Specific Antigen) can be used as a
      screening tool for detection of early prostate cancer However, a screening
      program for prostate cancer has not yet been accepted as cost-effective and long
      term survival benefits have not been shown. Nevertheless, some doctors request
      PSA testing in men who present with lower urinary tract symptoms (LUTS) to detect
      prostate cancer OBJECTIVE: To study for prevalence of prostate cancer in healthy
      men seeking medical check-up for prostate cancer. MATERIAL AND METHOD: During the
      anniversary celebration of Siriraj established day (26/07/1888), a cohort study
      of Prevalence of prostate cancer in aging males using PSA Screening Test was
      carried out, 200 men over 45 years of age were invited to PSA testing and
      prostate glands check-up including, IPSS (international prostatic symptoms
      score), QOL (quality of life score) and DRE (digital rectal examination).
      Patients with elevated PSA were advised to undergo transrectal-ultrasound-guided
      biopsy of the prostate (TRUS-biopsy). Cancer detection rate was calculated
      according to symptoms described by patients, IPSS and age groups. Data was
      compared using Chi-Square test. RESULTS: Median values from data of men's ages,
      IPSS, QOL and PSA were 63 years, 11, 2, and 1.23 ng/ml, respectively. 9 of 200
      patients (4.5%) were found to have prostate adenocarcinoma on biopsy. Most of the
      cancer cases showed a localized lesion. Prostate cancer was found more common in
      patients who described themselves as having abnormal urination. There was no
      prostate cancer found in patients with a mild degree of LUTS (IPSS less than 8).
      Prostate cancer tended to be more common in men with high IPSS. CONCLUSION:
      Screening prostate cancer by PSA testing detected the cancer in 4.5%. Most
      cancers were found on symptomatic patients. Patients with LUTS should be made
      aware of prostate cancer and PSA testing may be offered in such patients. However
      screening of prostate cancer in all men regardless of symptoms must wait for a
      larger study looking at long term survival benefit, cost-effectiveness of
      screening, and lastly, quality of life of patients on a screening program.

PMID- 16583580
TI  - Predicted outcome after repair of tetralogy of Fallot by postoperative pressure
      ratio between right and left ventricle.
AB  - BACKGROUND: The surgical management of tetralogy of Fallot (TOF) has continued to
      evolve and there are now generally excellent early and long-term results
      following complete repair. OBJECTIVE: To investigate the early results of the
      authors' current surgical management of TOF by assessing the perioperative and
      early to intermediate follow-up period. The authors paid particular attention to
      the post-operative ratio of right ventricular to left ventricular systolic
      pressure (RVSP/LVSP), focusing on the presence of low cardiac output, intensive
      care unit (ICU) stay, prolonged of inotropic support and ventilation support
      time. STUDY DESIGN: Retrospective study. MATERIAL AND METHOD: Between June 2002
      and August 2004, 31 consecutive patients underwent complete repair of TOF. Their
      mean age was 7.7 +/- 5.1 years (range, 2.9 to 25.3). A previous palliative shunt
      had been performed in 14 (45.2%) patients. Twenty-three patients (74.2%) were in
      NYHA FC II. Mean hematocrit and oxygen saturation were 50.9 +/- 10.25% and 80.5
      +/- 8.6%, respectively. Mean preoperative ratio of RVSP/LVSP was 1.1 +/- 0.15.
      The operative approach was transatrial/transpulmonary, and 17 (54.8%) patients
      required a transannular patch. An extracardiac valve conduit was necessary in 3
      (9.7%) patients with pulmonary atresia. RESULTS: There were no operative or late
      deaths. Two cases were reoperated from cardiac tamponade. Mean postoperative
      ratio of RVSP/LVSP was 0.53 +/- 0.16. Median ICU and hospital stays were 2.2 and
      11 days, respectively. Presence of low cardiac output and prolonged inotropic
      support were significantly (P < 0.05) related to a RVSP/LVSP ratio of more than
      0.5. At median follow-up of 6 months, 29 (93.5%) patients were asymptomatic and
      all patients were free of significant residual lesion. CONCLUSION: The authors'
      early results in complete repair of TOF patients are acceptable with a low
      incidence of morbidity. A postoperative RVSP/LVSP ratio of more than 0.5 was
      significantly associated to adverse outcome. Late complications may, however,
      develop, and long term follow-up for early detection of any such complications is
      essential.

PMID- 16583581
TI  - Can electrocardiogram electrodes replace bispectral index electrodes for
      monitoring depth of anesthesia?
AB  - BACKGROUND: Bispectral index has been introduced to provide optimal level of
      anesthesia. However, Bispectral index monitoring may not be cost effective in a
      relatively short procedures due to the high costs of the electrode. The authors
      conducted the present study to compare the feasibility of commercially available
      electrocardiogram (ECG) electrodes instead of the Bispectral index (BIS)
      monitoring. MATERIAL AND METHOD: The authors evaluated the difference in signal
      quality index (SQI) and BIS values collected from two BIS monitors, using ECG
      electrodes and BIS electrodes on the same patients before anesthesia, during
      light anesthesia, deep anesthesia and the emergence period Both sets of
      electrodes were placed at bifrontal areas throughout the procedure. Statistical
      analysis was evaluated by mean difference 95% confidence limits of agreement and
      visualized by Bland-Altman plot. A parametric analysis was analyzed using paired
      t-test. RESULTS: There were 390 parallel signal quality index and BIS values
      recorded in the present study. During anesthesia the mean BIS values were 58.63
      +/- 18.77 in the ECG electrode group and 56.99 +/- 19.84 in the BIS electrode
      group, which were not statistically different. The mean SQI values were 79.2 +/-
      24.8 and 82.8 +/- 21.6 using ECG electrodes and BIS electrodes, respectively. The
      mean difference between BIS values was 1.65 with 95% confidence limits of
      agreement between 0.91 and 2.38. CONCLUSION: Commercial ECG electrodes could be
      used for monitoring depth of anesthesia with clinically acceptable mean bias and
      95% confidence limits of agreement of BIS value obtained from BIS electrode.

PMID- 16583582
TI  - Improvement of diabetic care at Maharat Nakhon Ratchasima Hospital (the study of
      Diabcare-Asia from 1997 to 2003).
AB  - Diabcare-Asia, the largest, multicenter observational study in Asia, surveyed the
      status of diabetic control among Asian diabetics, including Thais. Maharat Nakhon
      Ratchasima Hospital is a regional hospital in Northeast Thailand that
      participated in Diabcare-Asia. In 1997, 1998 and 2003, the authors recruited 200,
      100, 204 diabetic patients for analysis, respectively. Most (93 per cent) of the
      patients had type 2 diabetes. In the present study, patients with a BMI > or = 25
      kg/m2 increased from 38, 45 and 47 percent in 1997, 1998 and 2003, respectively.
      Annual check-ups for diabetic complications increased to nearly 100 per cent by
      2003; however, only 72 per cent were examined for diabetic retinopathy, but that
      number is up from the 33 per cent in 1997. In the present study, diabetic
      retinopathy was detected in 8, 16 and 25 per cent of patients, respectively.
      Diabetic nephropathy (urine albumin > or = 1 + by urine strip) decreased from
      approximately 50 per cent in 1997/98 to 19 per cent in 2003. Patients were able
      to achieve the target blood sugar better than in the past. The number of patients
      with HbA1c < 7 per cent and FPG < or = 130 mg/dL was 8, 21, 38 and 30, 39 and 40
      per cent in 1997, 1998 and 2003, respectively. The proportion of patients who
      achieved the American Diabetic Association blood pressure, total cholesterol and
      LDL-C targets in 2004 was < 50 per cent. In conclusion, the present study showed
      the improvement of diabetic control at Maharat Nakhon Ratchasima Hospital between
      1997 and 2003. A similar hospital-based diabetic care system should be
      implemented at other Thai hospitals for the early identification and prevention
      of diabetic complications in the future.

PMID- 16583583
TI  - Hospital-acquired anemia.
AB  - OBJECTIVE: The incidence and etiologies of hospital-acquired anemia has not been
      well defined A prospective study was conducted to determine the incidence and
      etiologies of hospital-acquired anemia developed in patients admitted in the
      medical ward of a tertiary care university hospital. MATERIAL AND METHOD: All non
      anemic (hemoglobin (Hb) > or = 13 g/dl in male, > or = 12 g/dl in female)
      patients who were admitted to the general medical wards for at least 1 week,
      between March 2001 to October 2001, were included in the present study. Outcome
      of interest was anemia developed during hospital stay. The total volume of blood
      collected for investigations were recorded. RESULTS: Of the 98 evaluable
      patients, 64 (65.3%) developed anemia. Thirty-five percent of the patients had
      mild anemia (Hb > 10.0 g/dl) and 7% had severe anemia (Hb < or = 8.0 g/dl).
      Anemia of chronic disease was the most common cause found in 57.4% of anemic
      patients. Mean total volume of blood collected for investigation was higher in
      the anemic compared with the non-anemic group (147.0 ml vs. 52.0 ml, p < 0.05).
      Total volume of investigational blood also correlated significantly with degree
      of anemia (r = 0.638, p < 0.05). CONCLUSION: Anemia was a common complication
      occurring in almost two-thirds of patients admitted to the hospital. Even though
      anemia of chronic disease was the leading cause, investigational blood loss was
      also an important contributing factor.

PMID- 16583584
TI  - Acetylcholine receptor antibody in Thai generalized myasthenia gravis patients.
AB  - The authors studied acetylcholine receptor antibody (AChR Ab) in twenty-six Thai
      patients diagnosed as having generalized myasthenia gravis and fifteen control
      cases. AChR Ab assay was done by radio-immunoassay technique and reported by
      titer in nmole/L. The positive result was defined by titer more than 0.5 nmole/L.
      In the myasthenia gravis group, age ranged from 18 to 64 years old with mean of
      34 years old. The female: male ratio was 4.2:1. Duration of disease before taking
      blood sample ranged from 1 month to 14 years with a mean of 3.9 year The AChR Ab
      could be detected in 21 out of 26 patients (80.7%). In the control group, tests
      were all negative. The results of the test made the sensitivity of 80.7% and
      specificity of 100%. The positive predictive value was 100%, the negative
      predictive value was 75%, and the prevalence was 60.3%. There was no correlation
      between AChR Ab titer and clinical features. This test is a very valuable test in
      case of uncertainly in the diagnosis of myasthenia gravis.

PMID- 16583586
TI  - Nosocomial surgical site infection among Photharam Hospital patients with
      surgery: incidence, risk factors and development of risk screening form.
AB  - OBJECTIVE: A cross-sectional analytic study of 268 patients who received surgery
      at Photharam Hospital was conducted to assess the incidence and risk factors of
      nosocomial surgical site infection (SSI). MATERIAL AND METHOD: The studied
      patients who voluntarily participated and signed informed consents were
      interviewed Pus specimens from SSI patients diagnosed by use of CDC criteria were
      cultured After risk factor analysis, the risk screening form was developed and
      calculated by the Receiving Operating Curve. RESULTS: The results revealed that
      incidence of nosocomial SSI was 20.52% (55/268 cases). Of 55 SSIpatients, 45.46%
      were positive for bacterial culture. Risk factors for nosocomial SSI from
      univariate analysis were (a) age of patients > 60 years, OR = 1.91 (p = 0.043),
      (b) gender as male, OR = 2.20 (p = 0.024), (c) admitted ward as male surgical
      ward, OR = 2.42 (p = 0. 028), (d) current patients' illness as diabetes mellitus
      (DM), OR = 7.92 (p < 0.001) and tuberculosis, OR = 11.88 (p = 0.001), (e)
      abnormal ASA score, OR = 3.47 (p < 0.001), 60 smoking, OR = 3.72 (p < 0.001), (g)
      incorrect prophylactic drug use, OR = 2.98 (p = 0.002), (h) duration of admission
      > 10 days, OR = 4.87 (p < 0.001), and (i) wound dressing > 1 time/day, OR = 4.16
      (p < 0.001). After multiple logistic regression analysis, the significant risk
      factors were (a) current patient's illness as DM, OR = 14.43 (p = 0.005), (b)
      smoking, OR = 13.18 (p = 0.001), (c) duration of admission > 10 days, OR = 4.88
      (p = 0.032) and (d) wound dressing >1 time/day, OR = 23.32 (p < 0.001). The risk
      screening form was developed and showed approximately 65% sensitivity and 78%
      specificity when a cut-off score at risk > 18 was used CONCLUSION: This risk
      screening form should be considered in other hospitals. When a postoperative
      patients has a score of 18, they should be considered a potential risk for
      nosocomial SSI and preventive measures should be integrated to reduce the risk
      for nosocomial SSI.

PMID- 16583585
TI  - Accuracy of sixteen-slice CT scanners in detected coronary artery disease.
AB  - BACKGROUND: The coronary artery disease, now, the incidence is increasing in both
      developed and developing countries. The investigation is evoluted and non
      invasive multislice CT scanners have been used more frequently, although the gold
      standard is still the coronary angiography. OBJECTIVE: To investigate the
      accuracy in detected coronary artery disease by using 16-slice CT scanners
      compared to the conventional coronary angiography. MATERIAL AND METHOD: Fifty
      five patients were 43 males, 12 females, median aged 62 years (43-82 years), and
      average heart rates 67 beats/minute (46-147 beats/minute) had the ECG-gated CT
      angiography followed by coronary angiography in 3 months. The ECG-gated CT
      angiography was performed by using 16-slice MSCT detector (0.42-s rotation time,
      16 x 0. 75-mm detector collimation). RESULTS: All patients were classified into
      two major groups; one was significant coronary artery stenosis which was designed
      by stenosis at least 50% and the other was non-significant stenosis which was
      designed by normal or stenosis less than 50%. The site having blooming artifact
      due to calcification that causes complete obliteration of the lumen or having
      significant motional artifacts was ruled out. There were 285 evaluable sites in
      19 patients with high heart rates, more than 70 beats/minute. The sensitivity,
      specificity, and accuracy in significant stenosis were 72.9%, 99.6%, and 94.0%
      respectively. In 36 patients with a lower heart rate, there were 563 evaluable
      sites, the sensitivity was 86.5%, specificity was 98.5%, and accuracy was 96.6%.
      The overall showed 81.1% of sensitivity, 98.9% of specificity, and 95.8% of
      accuracy. CONCLUSION: The accuracy of the 16-slice CT angiography for patients
      suspected of having coronary artery disease was high. However, blooming artifacts
      from the calcium, respiratory artifacts, and small size of the distal and
      branching artery still caused limited luminal assessment. These problems have
      challenged the new coming generation of MDCT.

PMID- 16583587
TI  - Folliculectomy: management in segmental trichiasis and distichiasis.
AB  - OBJECTIVE: To propose a new surgical technique as an alternative method for the
      correction of segmental trichiasis and distichiasis. MATERIAL AND METHOD: An
      interventional case series reviewed the segmental trichiasis and distichiasis
      patients who were treated with folliculectomy in the Ophthalmology Department,
      King Chulalongkorn Memorial Hospital. The data was collected from January 1997 to
      December 2002. The history, clinical features and treatments were reviewed.
      Patients with the initial diagnosis of entropion were excluded. RESULTS: Nine
      segmental trichiasis and distichiasis patients (13 eyes) were reviewed. Eight
      eyes underwent folliculectomy and one had folliculectomy with anterior lamellar
      recession. The follow-up time was 1-24 months. Nine of thirteen eyes (69.2%) were
      successfully treated with folliculectomy or folliculectomy with anterior lamellar
      recession. Four eyes needed second operations due to the recurrence of the
      eyelashes. CONCLUSION: Folliculectomy revealed good results in trichiasis and
      distichiasis. It should be considered as an alternative technique because it is a
      simple and fast procedure.

PMID- 16583588
TI  - Rosai-Dorfman disease and juvenile xanthogranuloma in a Thai boy: report of a
      case.
AB  - A 3-year-old Thai boy suffered from two histiocytoses, Rosai-Dorfman disease
      (RDD) and juvenile xanthogranuloma (JXG). The patient first presented with
      massive cervical lymphadenopathy at the age of one year. Biopsy revealed typical
      RDD; abnormally large CD68- and S-100 protein-positive histiocytes with
      occasional emperipolesis filled up the sinuses. Two years later, he developed
      polyuria and polydypsia. Skull film demonstrated osteolytic lesions at the
      occiput and left parietal region. Enlargement of the pituitary stalk was found on
      the magnetic resonance imaging. Despite the clinical impression of Langerhans
      cell histiocytosis, biopsy of the occipital lesion disclosed numerous large
      histiocytes with foamy cytoplasm. Several Touton giant cells with wreath-like
      arrangement of the nuclei were also observed. The abnormal cells expressed CD68
      and factor XIIIa, but were non-reactive with S-100 protein and CD1a. Biopsy of
      the pituitary stalk was not performed According to the authors' literature
      search, this represents the first report of RDD and JXG affecting the same
      person.

PMID- 16583589
TI  - Floppy infant caused by MTM1 mutation: a first genetically-confirmed X-linked
      myotubular myopathy patient in Thailand.
AB  - Floppy infant syndrome (FIS) refers to a condition wherein an infant manifests
      generalized hypotonia since birth or in early life. It is heterogeneous and can
      be caused by various central nervous system disorders, neuromuscular diseases and
      genetic disorders. X-linked myotubular myopathy (XMTM) is a progressive
      congenital myopathy morphologically characterized by the presence of centrally
      placed nuclei in numerous muscle fibers without any other particular pathological
      abnormalities. Patients are frequently born with floppiness and respiratory
      distress. The vast majority of patients carry a truncating or missense mutation
      in MTM1. The authors report here a full term male baby with clinicopathological
      features of XMTM. The diagnosis is validated by the finding of a c. 141
      144delAGAA mutation ofMTM1. To the best of the authors' knowledge, the present
      case is the first genetically confirmed XMTM in Thailand. A brief review of
      various neuromuscular disorders causing floppy infant syndrome is also included.

PMID- 16583590
TI  - Fatal heroin intoxication in body packers in northern Thailand during the last
      decade: two case reports.
AB  - A body packer is an important means of drug trafficking. While drug packets are
      inside the body, they can leak or rupture causing acute substance toxicity. Most
      of the reports of body packer syndrome have come from Europe and North America,
      which are destination targets. In the present study, the authors reported two
      cases of fatal heroin body packers from the northern part of Thailand. Both cases
      were foreign tourists who came to Chiang Mai and stayed in a hotel or a
      guesthouse room in which the deaths occurred. The autopsy findings revealed
      rupturing of heroin packages in the stomach. The packaging used in both cases was
      not sophisticated. The powder was packed inside condoms without extra covering,
      as observed in some other professional packers. The amount of heroin transported
      was about 30-50 gm. The purity of heroin in this powder was about 50-90%. Their
      destinations were their home countries and not directly to Europe or North
      America. Deaths occurred just prior to their return. The cause of death was a
      heroin overdose. A significant level of heroin metabolites, 6-MAM and morphine
      were detected in the blood and urine.

PMID- 16583591
TI  - Introduction to stem cell medicine.
AB  - Embryonic stem cell is the promising novel therapeutic tool for various
      degenerative diseases and tissue injuries. With the concept of cell and tissue
      therapy, many chronic disorders will be curable. The present article provides
      basic knowledge of stem cell in areas of definition, classification and future
      clinical applications. In addition, stem cell application is not only focusing on
      regenerative purpose, but also concentrating on more understanding about the
      early human development and the pathophysiology of genetic diseases at the
      cellular level. However, there are some technical problems and ethical concern
      that should be resolved before applying stem cells into clinical practice.

PMID- 16583592
TI  - Comparison of two clinical methods for evaluating the anti-plaque efficacy of a
      dentifrice.
AB  - OBJECTIVE: The objective of this research was to assess two different published
      methods of plaque level evaluation on human subjects, and to determine whether
      both methods can produce similar findings to the point that the methods can be
      used interchangeably. METHODOLOGY: Healthy human volunteers entered into a number
      of double-blind, cross-over clinical trials. Two plaque scoring methods were
      used: The Modified Gingival Margin Plaque Index (MGMPI) and the Turesky Modified
      Quigley-Hein (TMQH). With the MGMPI, plaque was evaluated 24 hours after a single
      product use. With the TMQH, plaque was scored after four days of product use.
      Three dentifrices were studied: Colgate Total, Colgate Total plus Whitening, and
      Colgate Regular Dental Cream. Additionally, two mouthrinses were evaluated:
      PerioGard and Fluorigard. In all studies conducted, there was a one-week wash-out
      period between each product use. RESULTS: There were no side effects observed or
      reported in any study. In all studies, both the plaque indices used found that
      the active products Colgate Total, Colgate Total plus Whitening and PerioGard
      produced significantly lower mean plaque scores compared to Colgate Regular
      Dental Cream and Fluorigard (p < 0.05). CONCLUSION: The results of this
      investigation indicate that the two plaque evaluation methods continue to
      demonstrate that an active product is significantly more efficacious than a
      control product. Therefore, either method can be used to investigate the anti
      plaque efficacy of a product. Additionally, the MGMPI method can be used 24 hours
      after product use, which is a clear advantage over a four-day product use and
      will yield the same results.

PMID- 16583593
TI  - A study of benzocaine gel dosing for toothache.
AB  - OBJECTIVE: This pilot study evaluated subject compliance with a proposed OTC
      label with improved dosing directions for self-application of a 20% benzocaine
      gel for toothache pain, and assessed the methodology for evaluating efficacy in a
      future pivotal study of benzocaine gel. It was hypothesized that > or = 75% of
      subjects would apply < or = 400 mg of product (80 mg benzocaine). Exploratory
      analyses of efficacy were also performed. METHODOLOGY: Thirty patients with
      spontaneous pain of moderate or severe intensity from a single tooth due to
      caries, a lost restoration, or a fracture entered this randomized, parallel
      group, double-blind study. Before self-applying 20% benzocaine gel or placebo,
      patients read a label containing new dosing directions, including a picture of
      how much product to apply to their tooth and the surrounding gingival tissues.
      The amount applied was determined by weighing the tube before and after dosing.
      Following dosing, pain intensity and relief were recorded every five minutes
      through 30 minutes, then every ten minutes through 120 minutes. Responders were
      defined as those subjects who experienced at least a one-unit reduction in pain
      intensity from baseline at two consecutive time points within the first 20
      minutes. Onset of meaningful relief was recorded using a stopwatch. The
      percentage of responders was compared using the Mantel-Haenszel test. ANOVA was
      employed to test for differences in Pain Relief Combined with Pain Intensity
      Difference (PRID), and the areas under the curve at 30, 60, 90, and 120 minutes
      for this measure (SPRID). Median onset and duration times were compared using the
      Cox proportional hazards model. Adverse events were recorded if and when they
      occurred. RESULTS: It was found that 86.7% of the subjects (26/30) applied < or =
      375 mg of product (mean +/- SD = 327.7 +/- 276.8 mg). The benzocaine group had a
      significantly higher (p = 0.022) responder rate (86.7%) than the placebo group
      (46.7%). Significant differences in favor of the benzocaine group were also
      recorded for PRID at 10, 15, and 30 minutes (p < 0.05) and SPRID-30 (p = 0.037).
      Median onset and duration times were 8.3 minutes and > 115 minutes for the
      benzocaine group, >120 minutes and 5 minutes for the placebo group. There were no
      adverse events recorded in the study. CONCLUSION: The improved dosing directions
      resulted in a high percentage of subjects self-applying an appropriate amount of
      benzocaine gel or matching placebo. The label and study methodology appear
      suitable for a pivotal dose-response study in subjects with toothache pain. While
      the current study was not statistically powered to make firm efficacy
      conclusions, 20% benzocaine gel appeared more efficacious than placebo, providing
      a rapid onset of pain relief and a relatively long duration of action.

PMID- 16583594
TI  - A clinical trial of the meridol toothbrush with conical filaments: evaluation of
      clinical effectiveness and subjective satisfaction.
AB  - OBJECTIVE: The present study was designed to evaluate the health promotion
      effectiveness, especially at the gingival margin, and the subjective satisfaction
      of a new toothbrush with soft conical filaments. METHODOLOGY: Sixty-eight healthy
      adult subjects participated in the clinical trial and were randomly divided into
      a test group (meridol toothbrush) or control group (standard ADA reference
      toothbrush). Subjects were given oral hygiene instructions and a pre-study
      cleaning by a dental hygienist. Clinical examinations included the Gingival Index
      (GI), Bleeding Index (BLI), and Patient Hygiene Performance Index (PHP) for
      plaque levels (before and after brushing), and were conducted at baseline, 30,
      and 60 days. A self-administered satisfaction questionnaire was applied at 30 and
      60 days. The statistical test employed for change within each test group was
      repeated measures ANOVA, and ANCOVA was employed for between-group analysis. For
      measures of satisfaction, Fisher's Exact test was applied when comparing the
      percentages of answers. RESULTS: For the GI, the test group demonstrated a highly
      significant statistical decrease (from GI = 0.22 to GI = 0.13, p = 0.0004). The
      control group showed less of a decrease with statistical significance (GI = 0.21
      to GI = 0.16, p = 0.05). For the BLI, the test group also demonstrated a highly
      significant statistical decrease (from BLI = 0.29 to BLI = 0.11, p = 0.0013),
      while the control group showed a very small decrease with no statistical
      significance (BLI = 0.24 to BLI = 0.17). The analyses of the PHP plaque levels
      after brushing showed significant and similar decreases for both groups over the
      study period (test group: p = 0.04, controls: p = 0.01). In an analysis of PHP
      before brushing, both brushes showed increases from baseline to day 30. This
      increase continued from day 30 to day 60 for the control group. For the test
      group, there was a significant decrease from day 30 to day 60 (PHP = 0.84 to PHP
      = 0.75, p = 0.037). For satisfaction, a significantly higher percentage of test
      subjects expressed that the brush was "pleasant to use" as compared to controls,
      both at 30 and 60 days (77% vs. 48%, p = 0.02, 80% vs. 54%, p = 0.04,
      respectively). CONCLUSION: The initial increase in plaque levels (before
      brushing) in the test group, is explained as a possible "learning curve" effect
      of using this new and unconventional brush. It is suggested that the conical
      filaments clean the subgingival pockets and that this is of important gingival
      health potential. This subgingival cleansing might not be adequately detected by
      the PHP index. These results might indicate a gingival health promotion potential
      for this toothbrush with conical filaments.

PMID- 16583595
TI  - In vitro evaluation of antibacterial activities of root canal sealers.
AB  - OBJECTIVE: The purpose of this study was to compare the antimicrobial effect of
      AH-26 (a resin-based sealer), Dorifill (a ZOE-based sealer), and pure ZOE after
      24 hours and after one week. METHODOLOGY: All sealers were prepared according to
      the manufacturers' directions immediately before testing. The micro-organisms
      used in this assay included Staphylococcus aureous and Streptococcus mutans,
      which were prepared from isolated species in the microbiology laboratory. The
      antimicrobial effects of each sealer were determined by measuring the diameter of
      the zone of inhibition in millimeters after incubation at 37 degrees C for 24
      hours and seven days in a humid atmosphere. Each test was repeated three times.
      RESULTS: In the 24-hour samples, the antibacterial activity of AH-26 was
      significantly greater than two other materials tested on both bacteria (p <
      0.05). The antibacterial activity of Dorifill and ZOE on S. aureous was not
      significantly different from each other (p > 0.05), but Dorifill had a
      significantly greater effect on S. mutans than ZOE (p < 0.05). In the seven-day
      samples, statistically significant zones of bacterial growth inhibition for both
      bacterial species tested were observed in descending order of antibacterial
      activity as ZOE > AH-26 > Dorifill (p < 0.05). CONCLUSION: The products studied
      exhibited some variable antibacterial properties. In 24 hours, the AH-26 exerted
      the greatest activity against both organisms tested. By seven days, the ZOE-based
      sealer-Dorifill-showed lower antibacterial activity than AH-26 and pure ZOE.

PMID- 16583596
TI  - Analysis of the antibacterial activity and plaque control benefit of colgate
      total dentifrice via clinical evaluation and real-time polymerase chain reaction.
AB  - OBJECTIVE: This study analyzed, from a combined clinical and molecular biologic
      perspective, the antibacterial and antiplaque efficacy of Colgate Total
      dentifrice (CTD). METHODOLOGY: A single-blind crossover study design utilized 11
      healthy human subjects. After a one-week washout period, subjects donated dental
      plaque, received a dental prophylaxis, and subsequently brushed with a test
      product. Twenty-four hours postbrushing, dental plaque was collected and a
      clinical plaque score determined. Dental plaque was submitted for Real-time
      Polymerase Chain Reaction (Real-time PCR) analysis. The same procedure was
      repeated in accordance with a crossover design for the use of the second test
      product. Following a one-week washout, a plaque donation, prophylaxis, and
      brushing with the test product ensued for each subject. Twenty-four hours post
      brushing, the subjects returned for a plaque score and plaque donation. RESULTS:
      Twenty-four hours after brushing, dental plaque coverage increased 17.88% +/-
      8.27% with CTD, compared to 30.42% +/- 9.97% with Colgate Cavity Protection (CCP;
      p = 0.005). Real-time PCR found plaque collected 24 hours after brushing with CTD
      exhibited, on average, fewer representative periodontal pathogens (Fusobacterium
      nucleatum, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, and
      Porphyromonas gingivalis) and fewer early colonizers (Actinomyces naeslundii)
      than plaque collected before brushing, whereas CCP showed a moderate effect on
      oral bacteria. CONCLUSION: The study provides clinical and molecular biological
      evidence to substantiate the antibacterial and plaque control benefits of Colgate
      Total, and suggests the value of combining a molecular biological method with
      clinical research to corroborate clinical benefits.

PMID- 16583597
TI  - Clinical evaluation of a novel dental whitening lamp and light-catalyzed peroxide
      gel.
AB  - OBJECTIVE: This study examined whether an ultraviolet light enhanced the
      whitening efficacy of a peroxide gel containing a photo-Fenton activator.
      METHODOLOGY: Fifty subjects were enrolled into the trial at two geographically
      separate sites. As directed by the randomization keys, teeth of half of the study
      subjects were concurrently exposed to the whitening lamp, while the gel was on
      their teeth, for a total light exposure of 45 minutes. The other half of the
      subjects received no light treatment. At each examination, clinical data were
      collected on the gingival index, shade score, and self-assessed dentinal
      hypersensitivity. RESULTS: Changes in tooth shade were significantly better
      (approximately 26% improvement; p < 0.05) for subjects exposed to the gel and
      dental whitening lamp (average = 7.7 shade changes) compared to subjects exposed
      to the gel only (average 6.1 shades) immediately after treatment. No reports of
      erythema, desquamation, ulceration of soft tissues, gross changes in teeth,
      gingiva, or restorations were documented. The relative changes in mean
      sensitivity scores were similar for both groups, with no significant differences
      between the Light and No-light groups at any interval. CONCLUSION: The whitening
      effect was improved by approximately 26% when the Zoom2 dental whitening lamp was
      used. It was demonstrated that the a photo-Fenton activator used with a bleaching
      light and 20% hydrogen peroxide gel is safe and effective for whitening teeth
      rapidly.

PMID- 16583598
TI  - Advanced oral antibacterial/anti-inflammatory technology: A comprehensive review
      of the clinical benefits of a triclosan/copolymer/fluoride dentifrice.
AB  - INTRODUCTION: Triclosan is a broad-spectrum antibacterial agent, marketed for use
      in oral products. It is effective against both gram-positive and gram-negative
      bacteria. PVM/MA is the non-proprietary designation for a polyvinylmethyl ether
      maleic acid copolymer. It has been demonstrated that there is a greater uptake of
      triclosan to enamel and buccal epithelial cells from the use of a fluoride
      dentifrice containing triclosan and the PVM/MA copolymer than from a dentifrice
      containing triclosan alone. This Supplement details the results of antibacterial,
      anti-inflammatory, and short- and long-term plaque and gingivitis studies with a
      triclosan/copolymer/ fluoride dentifrice. Additionally, the Supplement reviews
      studies on the effect of a triclosan/copolymer/fluoride dentifrice on
      periodontitis, calculus, caries, whitening and stain removal, oral malodor, and
      on the microflora. CONCLUSION: Clinical studies indicate that the use of a
      triclosan/copolymer/fluoride dentifrice (Colgate Total Toothpaste) may provide
      oral health benefits beyond those associated with "traditional" toothpaste use,
      in a manner that is safe and effective. Studies presented in this Supplement
      demonstrate that Colgate Total Toothpaste provides superior protection against
      plaque and gingivitis, caries, oral malodor, exhibits superior stain removal, and
      provides protection against the progression of periodontal disease.

PMID- 16583600
TI  - State of the registered nurse workfore in the United States.
AB  - In this final installment of this exclusive six-part series on the state of the
      RN workforce in the United States, the authors summarize the major findings of
      each piece and offer specific and actionable recommendations for nurse leaders,
      educators, and policymakers.

PMID- 16583599
TI  - It takes a village.

PMID- 16583601
TI  - Perceptions of empowerment and intent to stay.
AB  - Investigating why nurses remain in organizations may serve as a stepping stone
      for future retention strategies. The relationship between intent to stay and
      workplace empowerment in nurses are described in this continuing education
      article.

PMID- 16583602
TI  - Antecedents and consequences of nurse managers' perceptions of organizational
      support.
AB  - The antecedents and consequences of nurse managers' perceptions of organizational
      support were evaluated. Study results revealed that changeable work environment
      factors are important precursors of perceptions of organizational support, which,
      in turn, result in positive work attitudes and better health.

PMID- 16583604
TI  - Linking nursing workload and performance indicators in ambulatory care.
AB  - More and more ambulatory care organizations are using nursing report cards to
      monitor and evaluate the quality and effectiveness of nursing care in the
      ambulatory setting. Nurse staffing levels is usually one of the items included in
      a nursing report card and the one most scrutinized by ambulatory care
      administrators. One strategy employed by the nursing leadership at the South
      Texas Veterans Healthcare System to justify nurse staffing levels is linking
      administrative staffing monitors with nurse-sensitive outcomes via workload and
      performance indicators. Through this approach, nurse leaders are able to justify
      nurse staffing level changes, needed technology changes, process improvements,
      and/or workflow needs to administrators with positive results and support.

PMID- 16583603
TI  - Occupational health nurses and case management.
AB  - Employers, providers, consumers, regulators, and society are demanding a
      systematic method to determine quality and cost efficiency in the provision of
      health care services in a multidisciplinary continuum of care within a reasonable
      time limit. Societal and legislative pressure on employers to incorporate and
      accommodate workers with disabilities or limitations and rising health insurance
      costs have urged organizations to set up effective strategies. An overview of the
      historical evolution of case management, trends in engaging workers in a
      successful return to work process, and a case study are presented.

PMID- 16583605
TI  - Managing people or places?
AB  - Based upon a growing body of nursing research, emphasizing the management of the
      work environment is more likely to lead to strong individual and organizational
      performance than focusing on individual performance. In several studies,
      individual variables among staff such as age, experience, and tenure were less
      predictive of their perceptions of an organization than were variables in the
      work environment.

PMID- 16583606
TI  - Megatrends, the annual report, possibilities.
AB  - The successful leader and manager have two very important challenges: to scan the
      horizon and not be thrown into crisis by not seeing predictable surprises, and to
      recognize the longer, more pervasive trends that are in the distant future. An
      annual autopsy of the past year and a review of the years ahead will not only
      fulfill the requirements for an annual report, but will be a learning experience
      for the team. When we are open to new ideas, lead by inviting dialogue rather
      than demanding, and openly trust, believe in, and inspire others, the
      organization will also adopt these values as its operating framework. Our annual
      plans will then be living documents that create the roadmap for excellence.

PMID- 16583608
TI  - The right time and place for technology. Interview by Robert Neil.

PMID- 16583607
TI  - A successful re-entry program.
AB  - Many programs have been invented or re-invented to help cope with nursing
      shortages. Although re-entry is not a new program, most are thought not to be
      successful. Emory Hospitals in Atlanta, Georgia designed a Re-entry Program in
      2000 that is still in place and has had 105 nurses successfully complete the
      program.

PMID- 16583610
TI  - A study in washing and sterilization.

PMID- 16583609
TI  - A Six Sigma approach to meeting patient demand. How to optimize inventory.

PMID- 16583611
TI  - Aligned schedules make OR and materials more efficient.

PMID- 16583612
TI  - A goal for four. Hospital system centralizes purchasing, standardizes.

PMID- 16583613
TI  - Partnering to improve the supply chain.
AB  - Successful materials management extends far beyond the hospital walls. More than
      ever, effective materials managers are partnering with suppliers, distributors,
      manufacturers and group purchasing organizations to reduce costs, improve
      inventory control and increase operational efficiency. This requires partners who
      are intimately familiar with both the unique requirements of individual health
      care settings and best practices throughout the industry. Beyond achieving better
      balance-sheet results, this consultative approach ultimately leads to
      standardized, proven processes that help ensure quality care is delivered safely.
      Health Forum convened a group of health care executives and industry vendors Nov.
      4, 2005, in Chicago to discuss hospital-vendor partnerships. The closed-door
      dialogue focused on how hospitals can work with vendors to improve operations.
      Health Forum would like to thank all of the participants for their open and
      candid discussion, as well as the sponsors for supporting this event.

PMID- 16583614
TI  - Fueled by price increases, materials managers fight back.

PMID- 16583615
TI  - Chemical sensors market still dominating biosensors.

PMID- 16583616
TI  - System marks new method of preventing wrong-site surgery.

PMID- 16583617
TI  - There's more than one way to effectively maintain equipment.

PMID- 16583618
TI  - Further insight on amylase and lipase.

PMID- 16583619
TI  - Praise for phlebotomists.

PMID- 16583620
TI  - Serum tumor markers: part II--practical considerations and limitations of
      testing.
AB  - The attributes of an ideal tumor marker are well beyond the capacity of the tests
      that are currently available. While some markers do an adequate job at the early
      detection of recurrence and as a means to monitor the efficacy of treatment,
      there are serious deficits regarding sensitivity and specificity. In addition,
      although they are easily measured and cost-effective, the limitations of
      immunoassays are also a detriment. PSA was used to illustrate many of the
      limitations and difficulties associated with tumor marker testing and cancer
      assessment. For the most part, however, it is a better marker than many of the
      other analytes examined for their corresponding malignancies. Nevertheless, PSA
      still has major limitations--as is the case for all tumor markers in current use.
      Although the use of tumor markers is widespread and they do have much to offer,
      clinicians need to be made aware of their limitations, which can be achieved
      through good communication between laboratorians and the caregivers who are
      ordering the tests.

PMID- 16583621
TI  - Occult hepatits C virus persistence: identification and characteristics.

PMID- 16583622
TI  - Design a lean laboratory layout.

PMID- 16583623
TI  - Passion drives genetics.

PMID- 16583624
TI  - The art of professional blood collecting.

PMID- 16583625
TI  - Pediatric autopsy registry studies infant mortality.

PMID- 16583626
TI  - Knowing when to re-read pathology reports is crucial.

PMID- 16583627
TI  - The government wants to know.

PMID- 16583628
TI  - Limiting conflicts of interest arising from physician investment in specialty
      hospitals.

PMID- 16583630
TI  - Neodymium:YAG laser anterior capsulotomy for capsular contraction syndrome.
AB  - BACKGROUND AND OBJECTIVE: This study presents the outcome of neodymium:YAG laser
      anterior capsulotomy for capsular contraction syndrome, the safety profile and
      effectiveness of which are unclear. PATIENTS AND METHODS: Records of 32 patients
      with a minimum of 3 months of follow-up were reviewed retrospectively. The
      procedure was considered successful if all of the following criteria were met:
      centered intraocular lens (IOL) or no obvious change in IOL centration post
      capsulotomy, no evidence of re-phimosis in the follow-up period; and no further
      requirement for surgical intervention due to capsular contraction syndrome in the
      follow-up period or complications were recorded. RESULTS: The procedure was
      successful in 25 case; (78%). Failed cases (n = 7, 22.0%) included 5 cases of re
      phimosis and 2 cases with progressive IOL decentration. The failure rate was
      higher in cases with preoperative IOL decentration (P< .01). CONCLUSION:
      Neodymium:YAG laser anterior capsulotomy was successful in the majority of cases.
      The failure rate was higher with preoperative IOL decentration.

PMID- 16583631
TI  - Intracameral 2.3% sodium hyaluronate to treat postoperative hypotony in patients
      with glaucoma.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the intracameral use of Healon5 (2.3%
      sodium hyaluronate) (Advanced Medical Optics, Santa Ana, CA) in patients with
      hypotony. PATIENTS AND METHODS: Fifteen consecutive patients with glaucoma who
      had hypotony for at least 7 days were prospectively recruited. Indications for
      the intracameral injection of Healon5 were an intraocular pressure (IOP) of less
      than 6 mm Hg with negative results on Seidel test. RESULTS: The mean IOP readings
      at baseline, 1 to 2 weeks post-injection, and 4 to 6 weeks post-injection were
      3.8 +/- 1.58, 6.58 +/- 2.62, and 6.50 +/- 2.24 mm Hg, respectively. The increase
      in IOP at both follow-up points was significant (P < .01). The visual acuity
      improvement was small but significant at the 4 to 6 week point (P = .05). In the
      early-onset cases, IOP increased significantly from baseline at both follow-up
      points (P< .05), but visual acuity did not. No significant change from baseline
      IOP or visual acuity occurred among the late-onset cases. The existing hypotony
      related conditions consistently improved by the 4 to 6 week point. CONCLUSIONS:
      Intracameral injection of Healon5 raised IOP more in early-onset hypotony cases
      than in late-onset cases. Although the improvements in IOP and visual acuity were
      statistically significant, the overall clinical picture did not change because
      the endpoint IOP was still hypotonus. Twenty percent of the patients had IOP
      spikes that required medical treatment.

PMID- 16583629
TI  - Combined pars plana vitrectomy and cataract surgery: outcome of
      phacoemulsification versus manual extracapsular cataract extraction through a
      sclerocorneal tunnel.
AB  - BACKGROUND AND OBJECTIVE: To compare the results of combined pars plana
      vitrectomy and cataract extraction with intraocular lens implantation by
      phacoemulsification versus manual extracapsular cataract extraction through a
      sclerocorneal tunnel. PATIENTS AND METHODS: Retrospective chart review of all
      patients who underwent combined pars plana vitrectomy with intraocular lens
      implantation and phacoemulsification or extracapsular cataract extraction through
      a sclerocorneal tunnel between March 1992 and July 2002. RESULTS: Fifty-four eyes
      of 51 patients were evaluated. Mean age was 69.68 +/- 9.11 years, and mean follow
      up was 9 months. Phacoemulsification was performed in 35 cases (64%) and manual
      extraction in 19 cases (36%). Visual acuity improved from mean logarithm of the
      minimal angle of resolution 1.69 +/- 0.54 before surgery to 1.22 +/- 0.76 after
      surgery. There was a greater improvement of visual acuity in the
      phacoemulsification group (0.59 +/- 0.67) than in the extracapsular cataract
      extraction group (0.22 +/- 0.68) (P = .06). Final visual acuity was correlated to
      the vitreoretinal pathology. Ultrasound biomicroscopy showed well-positioned
      foldable or rigid intraocular lens in the bag or in the sulcus. CONCLUSION:
      Combined cataract extraction by phacoemulsification or extracapsular cataract
      extraction through sclerocorneal tunnel and pars plana vitrectomy are safe and
      effective procedures.

PMID- 16583632
TI  - Tear meniscus evaluation by optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: To assess the ability of optical coherence tomography
      to visualize the inferior tear meniscus and measure its height. PATIENTS AND
      METHODS: Twenty-seven eyes (27 patients) with aqueous tear deficiency were
      compared with 20 eyes (20 patients) with normal tear secretion (control group).
      After the instrument was focused on the ocular surface, a 4-mm long vertical
      scan, centered on the lower tear meniscus at corneal 6 o'clock hours, was
      obtained using optical coherence tomography. Tear meniscus height was measured by
      means of an external application. RESULTS: Mean tear meniscus height was
      significantly lower (P < .0001) in patients with aqueous tear deficiency (mean +/
      standard deviation: 0.13 +/- 0.07 mm) than in the control group (mean +/-
      standard deviation: 0.25 +/- 0.08 mm). CONCLUSION: Optical coherence tomography
      can be used to noninvasively visualize the inferior tear meniscus. This method
      seems able to discriminate between patients with normal and dry eyes when
      measuring tear meniscus height.

PMID- 16583633
TI  - Optical coherence tomography of idiopathic juxtafoveolar telangiectasia.
AB  - BACKGROUND AND OBJECTIVE: To document optical coherence tomography (OCT) findings
      in a series of eyes with group 2A idiopathic juxtafoveal telangiectasia. PATIENTS
      AND METHODS: This study is a retrospective review of patient charts, OCT, fundus
      photography, and fluorescein angiography involving 23 eyes (12 patients). Mean
      retinal thickness in 9 macular areas was calculated and compared to previously
      published measurements from normal eyes. RESULTS: OCT in 8 of 13 stage 3 eyes
      revealed foveal cysts without evidence of cystoid macular edema on fluorescein
      angiography or biomicroscopy, and 1 lamellar hole. In stage 3 eyes, mild retinal
      thickening was found in 7 of 9 macular areas (P < .05). CONCLUSIONS: OCT commonly
      reveals foveal cysts in stage 3 idiopathic juxtafoveal telangiectasia. Consistent
      findings of associated mild macular thickening and lack of late petaloid
      hyperfluorescence on fluorescein angiography suggest that these cysts differ in
      pathophysiology from cystoid macular

PMID- 16583634
TI  - Expression of four growth factors in recessed extraocular muscles of rabbits.
AB  - BACKGROUND AND OBJECTIVE: The study was designed to determine the temporal
      expression of insulin-like growth factor (IGF)-I, IGF-II, basic fibroblast factor
      2 (bFGF-2), and transforming growth factor beta 1 (TGF-beta1) in recessed
      extraocular muscles. MATERIALS AND METHODS: Sixteen eyes of eight rabbits were
      subjected to conventional 4-mm recession of superior rectus muscles. Two rabbits
      were untreated as control. The rabbits were killed and their eyes were enucleated
      at 3 (group 3), 6 (group 6), 24 (group 24), and 72 (group 72) hours after the
      operation (two rabbits per group), and the expression of IGF-I, IGF-II, bFGF-2,
      and TGF-beta1 was immunohistochemically examined. RESULTS: The peak levels of IGF
      I, IGF-II, and TGF-beta1 expression were observed in groups 24, 6, and 3,
      respectively. However, bFGF-2 was less expressed than the other growth factors in
      all groups. CONCLUSIONS: IGF-I, IGF-II, bFGF-2, and TGF-beta1 in regenerating
      muscle cells were expressed by different kinetics, suggesting a distinct role of
      each growth factor during wound healing after recession of extraocular muscles.

PMID- 16583635
TI  - Ultrahigh-resolution optical coherence tomography of canthaxanthine retinal
      crystals.
AB  - A case of crystalline retinopathy caused by prolonged ingestion of an oral
      tanning agent containing canthaxanthine is described. Color fundus photography
      and ultrahigh-resolution optical coherence tomography were performed.

PMID- 16583636
TI  - Application of transpupillary thermotherapy in a patient with asteroid hyalosis
      and premacular hemorrhage.
AB  - A 70-year-old woman with long-term poor vision was found to have unilateral
      massive premacular hemorrhage and asteroid hyalosis. Transpupillary thermotherapy
      (TTT) was applied sequentially to the vitreous in four separate spots, covering
      the area of the asteroid hyalosis and hemorrhage. Outcome measures included
      visual acuity, biomicroscopic appearance, ultrasonography, and fluorescein
      angiography. Significant resolution of the hemorrhage was observed 3 months after
      TTT, with visual acuity improvement from counting fingers at 25 cm to 20/60.
      There were no complications noted during the procedure or during follow-up. The
      long-term safety measures and visual prognosis following TTT for resolution of
      the vitreous impurities remain to be evaluated, but the procedure may be
      effective for treating premacular hemorrhage and asteroid hyalosis.

PMID- 16583637
TI  - Intravitreal bevacizumab in a patient with neovascular glaucoma.
AB  - The utility of intravitreal bevacizumab injection in a patient with neovascular
      glaucoma following central retinal vein occlusion is explored. Bevacizumab (1 mg
      in 0.04 mL) was used after failed intraocular pressure (IOP) control with
      transscleral cyclophotocoagulation and panretinal photocoagulation. IOP improved
      within 2 days and the patient experienced marked improvement in comfort.
      Bevacizumab may be an effective medication for the treatment of neovascular
      glaucoma.

PMID- 16583638
TI  - Needle bleb revision of encapsulated filtering bleb with bevacizumab.
AB  - The utility of needle bleb revision with bevacizumab in a patient with a failing
      bleb following trabeculectomy is explored. The patient had previously failed
      needle bleb revision with mitomycin C. After needling and injection of 1 mg of
      bevacizumab, the bleb was noted to be more diffuse with a decrease in surface
      neovascularization. Bevacizumab may be an effective medication for rescuing
      failing filtering blebs that exhibit neovascularization.

PMID- 16583639
TI  - Anterior scleral buckling procedure for cyclodialysis cleft with chronic
      hypotony.
AB  - Cyclodialysis clefts occur when the attachment of the ciliary body to the scleral
      spur is disrupted. The mechanism is usually traumatic or iatrogenic after
      phacoemulsification or other intraocular manipulation. Treatment becomes
      necessary when hypotony occurs, with maculopathy being the most visually
      significant sequela. A patient who failed conventional treatment for hypotony and
      eventually benefited from a novel surgery to correct his cyclodialysis cleft is
      described.

PMID- 16583640
TI  - Peribulbar oncocytoma: high-frequency ultrasound with histopathologic
      correlation.
AB  - The clinical, ultrasonographic, and histopathologic characteristics of an
      oncocytoma of the conjunctiva are described. A 49-year-old woman presented with a
      red-orange lesion adjacent to the caruncle in her left eye. A clinical
      examination including high-frequency ultrasound was performed prior to excisional
      biopsy of her tumor. High-frequency ultrasound demonstrated an epibulbar tumor
      with low internal reflectivity and a cystic component. There was no involvement
      of the underlying sclera. Multiple hypoechoic components of the tumor stroma were
      correlated to multiple cystic glandular structures on histopathologic evaluation.
      The excised tumor was diagnosed to be an oncocytoma.

PMID- 16583641
TI  - Manual enucleation of both eyes during assault.
AB  - Manual enucleation of the eyeball from the orbit during physical assault is rare.
      Management includes removal of such sightless eyeballs when the optic nerve and
      extraocular muscles are avulsed. However, other authors recommend replacement of
      these eyeballs even though visual prognosis is nil and phthisis bulbi is
      expected. A patient who had bilateral enucleation after assault is described.

PMID- 16583642
TI  - Removal of benzyl alcohol from a commercially available triamcinolone acetonide
      suspension for intravitreal use.
AB  - Purification of commercially available formulations of triamcinolone acetonide is
      important to avoid potential toxic effects of the vehicle for intravitreal use.
      In 2004, a simple and rapid method to remove most of the vehicle with a
      centrifuge was reported. The aim of this article is to study the degree to which
      benzyl alcohol can be eliminated with this method. By means of a gas
      chromatographic procedure, it has been proven that centrifugation is suitable for
      removing most benzyl alcohol (ie, up to 95.5% at 10,000 rpm, 5 minutes), and it
      is better at modifying the concentration of the drug than other proposed methods
      (ie, decantation, filtering methods, or both).

PMID- 16583643
TI  - Development of a highly detailed virtual model eye.
AB  - Using a three-dimensional modeling computer program, the authors created a three
      dimensional, highly detailed computer-generated model of a normal eye to enhance
      the teaching of basic ophthalmic anatomy. The resulting model is a uniquely
      detailed virtual eye that can illustrate ocular anatomy clearly but realistically
      at many levels of magnification. Eye anatomy can be demonstrated from any
      viewpoint, with a choice of which structures are visible. The generation of video
      animations is also possible. The potential of this model for illustration of
      ocular disease will be the objective of further testing with medical students.

PMID- 16583644
TI  - A new high-power biconcave contact lens for observation and coagulation of the
      posterior segment.
AB  - A wide-angle, high-power negative contact lens was designed for observation and
      coagulation of the retina and choroid. The new contact lens has a lateral
      magnification of 0.44 and a field of view of 64 degrees. Due to the prismatic of
      its biconcave structure, the field of view may be shifted by tilting the lens,
      induced eye movements beyond the equator of the retina, or both. Because only a
      negative refractive surface is required, optical aberrations are significantly
      reduced. Safety during laser irradiation tasks is increased compared with the use
      of positive wide-angle contact lenses because the irradiance of the crystalline
      lens is significantly reduced.

PMID- 16583645
TI  - In vivo confocal microscopy of ocular cicatricial pemphigoid.

PMID- 16583647
TI  - Nursing facility codes.

PMID- 16583646
TI  - Patients aren't consumers.

PMID- 16583648
TI  - Implementing an EHR? No need to rush.

PMID- 16583649
TI  - Does the CMA have a silent PPO problem?

PMID- 16583650
TI  - One patient's suit saved another's life.

PMID- 16583652
TI  - Checking out job applicants.

PMID- 16583651
TI  - Straight talk about dying.

PMID- 16583654
TI  - Do your patients take your advice?

PMID- 16583653
TI  - Clip and copy. Doing a reference check.

PMID- 16583655
TI  - Adding ancillaries. Waived lab services.

PMID- 16583657
TI  - How to value your practice.

PMID- 16583656
TI  - Boost productivity? Walk less.

PMID- 16583658
TI  - How much insurance do you need?

PMID- 16583660
TI  - The perils and virtues of medical privacy.

PMID- 16583659
TI  - Culture gaps.

PMID- 16583661
TI  - Introduction: radiation oncology for the 21st century--the best is yet to be.

PMID- 16583662
TI  - Combination chemotherapy and radiation therapy for upper aerodigestive tract
      cancers.

PMID- 16583663
TI  - The role of palliative radiation in the management of brain, spinal cord, and
      bone metastases.

PMID- 16583664
TI  - Preoperative treatment of rectal cancer.

PMID- 16583665
TI  - Accelerated partial breast irradiation: current modalities and investigations.

PMID- 16583666
TI  - Radiation management of prostate cancer.

PMID- 16583667
TI  - Intensity modulated radiation therapy.

PMID- 16583668
TI  - Case of methemoglobinemia.

PMID- 16583669
TI  - Stage at diagnosis and first course of treatment for prostate cancer in Rhode
      Island, 1990-2003.

PMID- 16583671
TI  - Re commentary, "The Surgeon General: why not have one?".

PMID- 16583670
TI  - Images in medicine. A case of hypertrophic nerve roots.

PMID- 16583672
TI  - Family medicine in words.

PMID- 16583673
TI  - [Role of the basal ganglia in the occurrence of paradoxical sleep dreams
      (hypothetical mechanism)].
AB  - A hypothetical mechanism of the basal ganglia involvement in the occurrence of
      paradoxical sleep dreams and rapid eye movements is proposed. According to this
      mechanism, paradoxical sleep is provided by facilitation of activation of
      cholinergic neurons in the pedunculopontine nucleus as a result of suppression of
      their inhibition from the output basal ganglia nuclei. This disinhibition is
      promoted by activation of dopaminergic cells by pedunculopontine neurons,
      subsequent rise in dopamine concentration in the input basal ganglia structure.
      striatum, and modulation of the efficacy of cortico-striatal inputs. In the
      absence of signals from retina, a disinhibition of neurons in the
      pedunculopontine nucleus and superior colliculus allows them to excite neurons in
      the lateral geniculate body and other thalamic nuclei projecting to the primary
      and higher visual cortical areas, prefrontal cortex and back into the striatum.
      Dreams as visual images and "motor hallucinations" are the result of an increase
      in activity of definitely selected groups of thalamic and neocortical neurons.
      This selection is caused by modifiable action of dopamine on long-term changes in
      the efficacy of synaptic transmission during circulation of signals in closed
      interconnected loops, each of which includes one of the visual cortical areas
      (motor cortex), one of the thalamic nuclei, limbic and one of the visual areas
      (motor area) of the basal ganglia. pedunculopontine nucleus, and superior
      colliculus. Simultaneous modification and modulation of synapses in diverse units
      of neuronal loops is provided by PGO waves. Disinhibition of superioir colliculus
      neurons and their excitation by pedunculopontine nucleus lead to an appearance of
      rapid eye movements during paradoxical sleep.

PMID- 16583674
TI  - [Individual typological features reflected in different stages of learning and
      related changes in dopamine transport in the mesolimbic brain].
AB  - A hypothesis is proposed according to which there is a strong similarity between
      the individual typological features of animals (humans) and different stages of
      learning processes. The hypothesis is supported by the results of comparisons of
      psychophysiological and neurochemical indices of different stages of conditioning
      and various typologies of higher nervous activity. Such comparisons reveal a high
      similarity between the generalization phase and impulsivity, the phase a learned
      conditioned reflex and self-controlled behaviour, and overlearned CR and a state
      of "psychosis". Functional states close to pathology and possibilities of
      development and manifestation of several psychotic states depending on
      psychophysiological and neurochemical organization of learning processes are also
      considered.

PMID- 16583675
TI  - [Individual resistance to factors of monotony reflected in the EEG].
AB  - Three groups of operators substantially different in their performance quality
      were examined. Under conditions of monotonous activity, subjects with the highest
      initial level of activation, minimum EEG total spectral power, and minimum level
      of EEG coherence in the frontal cortical areas worked most steadily. Under the
      same conditions, subjects with a rather high spectral power of the theta and
      beta2 EEG frequency components, highest coherence in the frontal areas, and low
      coherence in the caudal areas of the cortex worked least steadily. EEG phenomena
      testify to a rather low level of activation of the frontal cortical areas
      associated with a facilitation of cortico-subcortical neuronal interactions and
      an attenuation of the operating neural streams. This results in a decrease in the
      level of any attention, its involuntary switching, and short-term loss of the
      control over the current performance.

PMID- 16583676
TI  - [Estimation of localization and dipole moment of alpha- and theta-rhythm sources
      by cluster analysis in healthy subjects and schizophrenics].
AB  - In 12 healthy subjects and 9 schizophrenic patients in the background conditions
      (with eyes closed) EEG was recorded from 16 standard derivations (10-20 system)
      during 3 min. The record underwent the spectral analysis detecting alpha- and
      theta-frequency bands. After the preliminary narrow band filtration for the main
      frequencies the sources of the spontaneous rhythms were localized. The data on
      localization for all healthy subjects and patients were summarized. The K-means
      clustering was used for identification of the sources clusters which were
      revealed in occipital and parietal lobes and limbic cortex for alpha-rhythm and
      also in frontal, temporal and parietal regions, limbic cortex and hippocampus for
      theta-rhythm. In schizophrenic patients in comparison with healthy subjects there
      was revealed significant increase of the numbers of dipole sources of alpha
      rhythm in the clusters localized in limbic cortex and hippocampus. For theta
      rhythm there was significant increase of the dipole moment of the sources in the
      clusters localized in the temporal and frontal cortices and hippocampus in
      patients in comparison with the norm.

PMID- 16583677
TI  - [Functional regional asymmetry of the EEG intrahemispheric coherence in dogs
      during conditioning].
AB  - Individual features of the regional interhemispheric relations in the brain were
      studied in dogs during alimentary conditioning. The electrical activity was
      recorded from symmetrical anterior (frontal and motor cortices) and posterior
      (visual and auditory cortices) areas of the neocortex. Comparison between the
      averaged left and right intrahemispheric EEG coherences revealed a dynamic
      character of interhemispheric relations dependent on the stage of conditioning.
      Individual features were shown. In a dog with strong type of the nervous system,
      in the anterior brain regions, the EEG coherence was higher in the left
      hemisphere than in the right one, whereas, on the contrary, in the posterior
      regions, the values were higher in the right than in the left hemisphere. In dogs
      with weak type of the nervous system, there was an inverse relationship. Thus,
      the spatial organization of the cortical electrical activity in the associative
      and projection brain areas was different.

PMID- 16583678
TI  - [Influence of emotional stimuli on behavior and respiration of rabbits with
      various locomotor activity in the "open field"].
AB  - Different behavioral reactivity of rabbit groups differentiated by locomotor
      activity in the "open field" was revealed during exposure to emotional stimuli
      (rustle, loud sound, pressuring on back of the neck, vibroacoustic tactile
      stimulation of an ear). In passive rabbits, the active locomotor reactions were
      induced harder and freezing was obtained easier than in active animals. During
      exposure to sound stimuli, passive rabbits increased their locomotion more rarely
      than active animals, pressing on back of the neck produced longer freezing, a
      threshold of defensive ear shaking in response to a vibroacoustic stimulus in
      passive animals was highest. Training to mild immobilization increased the
      threshold of defensive responses in active rabbits and animals of the
      intermediate type. Changes in respiratory parameters were correlated with
      behavioral reactions to emotional stimuli. The duration of exhalation and
      respiratory cycle increased during freezing and increased during enhanced
      locomotion. The duration of inhalation decreased in response to emotional stimuli
      irrespective of a behavioral reaction. The respiratory reactions to emotional
      stimuli differed in rabbits of different groups. The respiratory rate more
      frequently changed in passive rabbits than in animals of other groups. Passive
      animals reacted mainly by exhalation, active rabbits and animals from the
      intermediate group predominantly responded by inhalation.

PMID- 16583679
TI  - [Computation of responses to color and brightness differences of neurons in the
      rabbit lateral geniculate nucleus].
AB  - Changes in activity of 51 neurons in the rabbit lateral geniculate nucleus evoked
      by the replacement of eight color and eight achromatic stimuli in pairs were
      analyzed. It was found that neurons displayed the earliest phasic (within 50-90
      ms after the replacement) and tonic response components. The earliest component
      strongly correlated with differences between stimuli, whereas the tonic component
      depended on stimuli intensity. Analysis of phasic component revealed two neuronal
      populations: the first group of cells was specialized for stimuli differentiation
      only by their intensities, and, and the second group could measure differences in
      colors and intensities. Neuronal perceptual spaces were reconstructed using the
      average of the earliest response component as a measure of differences between
      stimuli. Spaces of 44 neurons (86%) were two-dimensional with brightness and
      darkness axes. Such neurons had the same structures of space for color and
      achromatic stimuli. Spaces of 7 neurons (14%) were four-dimensional with two
      chromatic and two achromatic axes. The structures of perceptual space
      reconstructed from neurons in the lateral geniculate nucleus were identical to
      the spaces calculated from the neurons in the primary visual cortex. The
      structure of the perceptual space reconstructed from neuronal spikes was also
      similar to space calculated from the N85 visual evoked potential component
      recorded under similar conditions and to another space reconstructed on the basis
      of rabbit's instrumental learning. This fact confirmed the general principle of
      vector coding in the visual system. The tonic component of the most of neurons in
      the lateral geniculate nucleus showed a linear correlation with changes in
      intensities, thereby these neurons could be characterized as pre-detectors for
      cortical selective detectors.

PMID- 16583680
TI  - [Citrulline extracellular level in the nucleus accumbens during acquisition and
      extinction of classical conditioned fear response with pain reinforcement].
AB  - By means of in vivo microdialysis combined with HPLC analysis, we have shown that
      extracellular levels of citrulline (NO co-product) and arginine (NO precursor)
      increase in the rat n. accumbens during acquisition and expression of a classical
      fear response. The conditioned rise of citrulline and arginine levels gradually
      decreased in the course of extinction. The renewal of the response produced an
      increase in extracellular citrulline and arginine levels. These data suggest that
      the acquisition of conditioned fear response causes an increase in NO production
      in the n. accumbens that weakens during the extinction and is restored during the
      reinstatement of the response.

PMID- 16583681
TI  - [The reorganization of bimanual movements during formation of a lateralized motor
      food skill in rats].
AB  - After 48 h food deprivation adult Wistar rats were trained to obtain food from a
      narrow tube feeder using the forepaw under conditions of free choice of limb. At
      the initial stage of training animals use both paws: the grasping and extraction
      with one paw can be alternated with food grasping and extraction with another
      paw, and both paws can be alternately involved in movements preceding this
      grasping. Character of reorganization of bimanual movements was analyzed during
      training rats with different motor preference (right-handed and left-handed
      animals). It was shown that in the process of acquisition of both right- and left
      hand skills, bimanual reactions in the anticipating attempts disappeared later
      than in the final successful movements. The disappearance of bimanual movements
      in the anticipating attempts is considered as an index of the maximum skill
      lateralization and acquisition of a novel lateralized movement coordination. The
      results suggest that left-handed rats more rapidly learn a novel movement
      coordination than right-handed animals.

PMID- 16583682
TI  - [Effector peptides of the brain renin-angiotensin system in central mechanisms of
      learned and natural forms of drinking behavior in rats].
AB  - Central mechanisms of angiotensin involvement in initiation and realization of
      operant forms of drinking behavior were investigated. It was suggested that
      intracerebroventricular microinjection of angiotensin-II and angiotensin-IIl
      specifically affected the learned forms of drinking behavior. The experiments
      demonstrated that [des-Asp1]-angiotensin-I produced only the natural forms of
      drinking behavior. Angiotensins modulated specific forms of thirst-associated
      behavior such as exploring, grooming, and ingestive behavior. Injections of AT1
      receptor antagonist losartan were associated with acute water intake decrease and
      sharp operant behavior inactivation.

PMID- 16583683
TI  - [Effects of D2 receptor agonist and antagonist on behavior of intact and
      ovariectomized rats].
AB  - The involvement of D2 dopaminergic receptors in behavioral responses during ovary
      cycle was assessed in adult intact female rats and ovariectomized (OVX) female
      rats. Quinperole (0.1 mg/kg), D2 receptor agonist and sulpiride (10.0 mg/kg), D2
      receptor antagonist were injected chronically to adult intact and ovariectomized
      (OVX) female rats either separately or in combination with 17beta-estradiol (0.5
      microg) within 14 days. Behavior of these animals was assessed in the "open
      field" test, whereas passive avoidance performance served as a model of learning.
      In intact rats, the passive avoidance performance was observed only in metestrous
      and diestrous. Chronic quinperole administration to intact females resulted in
      the appearance of the passive avoidance performance in proestrous and estrous, as
      distinct from the control animals. The passive avoidance performance was not
      reproduced in OVX rats. Quinperole per se or in combination with 17beta-estradiol
      completely restored the passive avoidance performance in OVX rats. Moreover,
      quinperole or sulpiride administration to OVX rats increased horizontal locomotor
      activity, exploratory behavior, and grooming behavior.

PMID- 16583685
TI  - Multidimensional confusion?

PMID- 16583684
TI  - [Aggressive behavior, its adaptive function and mechanisms of development of
      psychosomatic disorders and diseases of adaptation].
AB  - A correlation between physiologic and behavioral responses to emotional stress
      and agonistic conflict (triad model), as well as ideas of autonomic-humoral
      support of subsequent activity suggest that motor activity and situational
      aggressive behavior are essential final stages of stress reaction and, therefore,
      mechanisms of adaptation. Failure in final the stage of adaptive response causes
      mobilization changes to be directed against the host organism itself. This
      phenomenon forms the basis for psychosomatic disorders. Aggression seems to be an
      adaptive response not only from ethologic, but from physiologic point of view as
      well. It has some elements of homeostatic control (together with non-homeostatic
      functions). Homeostatic role of aggression may be in "elimination" of
      mobilization metabolic changes caused by stress reaction and physical activity by
      means of expressive emotional response. Aggression as a non-homeostatic factor
      has an ethologic function.

PMID- 16583686
TI  - Multidimensional liquid chromatography for sample characterisation.
AB  - While LC finds enormously widespread use in almost all areas of chemical science,
      the technique is limited as a means of identification because compounds do not
      elute with unique retention times. This limitation spurred the growth of
      hyphenated instrumental methods of analysis, such as LC-MS/MS, which because of
      the MS/ MS detection became a method of identification. However, techniques like
      LC-MS/ MS are specialised and require high initial purchase and running costs,
      inhibiting the more widespread growth of the technique. In an attempt to increase
      the separation power of LC, multi-dimensional LC was developed. This expanded the
      separation space and subsequently has allowed the development of methods with
      fingerprinting ability due to the lower probability of component overlap. The
      work in this study illustrates the application of 2-D LC as a means of chemical
      fingerprinting. We employed a sample base of various low molecular weight
      oligostyrenes and their diastereomers that represent a population of compounds
      whose selectivities in a one-dimensional separation are almost unity and hence
      essentially impossible to separate. Yet in a 2-D domain almost all individual
      components occupy unique 2-D retention times.

PMID- 16583687
TI  - Considerations on the possibilities and limitations of comprehensive normal phase
      reversed phase liquid chromatography (NPLC x RPLC).
AB  - A comprehensive normal phase system LC-reversed phase LC (NPLC x RPLC) was
      evaluated for the separation of a pharmaceutical mixture and citrus oil extracts.
      NPLC was performed on a 25 cm x 1 mm ID x 5 microm dp diol phase. In the second
      dimension, an RP 18 monolithic column (10 cm L x 4.6 mm ID x 2 microm macropore
      size) and an octadecyl silicagel-packed column (5 cm L x 4.6 mm ID x 3.5 microm
      dp) were applied for the analyses of the pharmaceutical sample and the citrus oil
      extracts, respectively. A two-position/ten-port switching valve was used as
      interface. Under optimised LC conditions, the high degree of orthogonality
      between NP and RP resulted in peak capacities of 300 for the pharmaceutical
      sample and of 450 for the citrus oil extract composed of lemon and orange oil.
      Despite the features of NPLC x RPLC, several shortcomings related with the
      solvent incompatibility between the two LC modes were identified and the
      practical consequences were discussed.

PMID- 16583688
TI  - Multi-dimensional HPLC/MS of the nucleolar proteome using HPLC-chip/MS.
AB  - The proteome of the human nucleolus was investigated in a single analysis using
      off-line strong cation exchange chromatography and microfraction collection
      combined with HPLC-chip/MS. The analysis was conducted either as a 1-D workflow
      with HPLC-chip alone or as a 2-D workflow. Two hundred and six unique proteins
      were identified in the International Protein Index human database corresponding
      to 2024 unique tryptic peptides identified in the 2-D analysis. In contrast, only
      34 proteins and 151 corresponding tryptic peptides were found by applying a 1-D
      separation strategy. This clearly indicated that the complexity of the samples
      required the combination of more than one orthogonal separation technique.
      Stringent database search criteria, including reversal of sequences and therefore
      better exclusion of false-positive identifications, were applied for reliable
      protein identification.

PMID- 16583689
TI  - Towards a comprehensive 2-D-LC-MS separation.
AB  - A comprehensive 2-D-LC-MS method has been developed by coupling columns of
      different selectivity. The primary column eluate is alternately trapped and
      sampled onto the secondary columns through a guard column interface. When one
      guard column traps the eluate, the other injects the previously trapped
      components onto a secondary column. This cycle is repeated throughout the
      chromatogram. The use of dual secondary columns provides the secondary columns
      with additional time to generate high-speed chromatograms. Each secondary column
      generates alternate chromatograms which when combined generate the entire
      chromatogram. The primary column separation is comparable to conventional HPLC,
      whereas the secondary column separation is fast. With both the columns operating
      in reverse phase mode, one would expect strong correlation in the two-dimensional
      retention and hence inefficiency in separation. However, differences in column
      operation modes, interaction mechanisms, and vendor silica result in a
      complementary separation. The system was evaluated by comparing it to one
      dimensional counterparts and coupled column chromatography. Although some
      correlations were observed in 2-D-LC-MS, peaks do show two-dimensional
      distribution with superior UV and MS data as co-elution is minimized. Also, the
      ease of converting conventional systems to 2-D-LC-MS is discussed.

PMID- 16583690
TI  - Fractionation and separation of human salivary proteins by pH-gradient ion
      exchange and reversed phase chromatography coupled to mass spectrometry.
AB  - In the present work, a 2-D capillary liquid chromatography method for
      fractionation and separation of human salivary proteins is demonstrated.
      Fractionation of proteins according to their pI values was performed in the 1-D
      employing a strong anion exchange (SAX) column subjected to a wide-range
      descending pH gradient. Polystyrene-divinylbenzene (PS-DVB) RP columns were used
      for focusing and subsequent separation of the proteins in the 2-D. The SAX column
      was presaturated with a high pH buffer (A) consisting of 10 mM amine buffering
      species, pH 9.0, and elution was performed with a low pH elution buffer (B)
      having the same buffer composition and concentration as buffer A, but pH 3.5.
      Isoelectric point fractions eluting from the 1-D column were trapped on PS-DVB
      trap columns prior to back-flushed elution onto the PS-DVB analytical column for
      separation of the proteins. The 1-D fraction eluting at pH 9.0-8.7 was chosen for
      further analysis. After separation on the RP analytical column, nine RP protein
      fractions were collected and tryptic digested for subsequent analyses by MALDI
      TOF MS and column switching capillary LC coupled to ESI TOF MS and ESI QTOF MS.
      Eight proteins and two peptides were identified in the pH 9.0-8.7 fraction using
      peptide mass fingerprinting and uninterpreted MS/MS data.

PMID- 16583691
TI  - Direct sensitive quantitative lC/MS analysis of C-peptide from human urine by two
      dimensional reverse phase/reverse phase high-performance liquid chromatography.
AB  - We describe for the first time the direct quantitative analysis of human C
      peptide from urine by isotope dilution assay. Implementation of 2-D reverse phase
      reverse phase chromatography (2-D RP-RP) with SIM detection resulted in high
      assay sensitivity (LOQ= 5 pg on column), accuracy, and method ruggedness. Our
      experiments demonstrate the strong resolving capability of our proposed 2-D RP-RP
      platform which significantly reduces strong matrix effects and their resulting
      quantitation error over a wide range of urine concentrations. In contrast, single
      column methods (both SIM and multiple reaction monitoring) were found acceptable
      only for strongly diluted urine samples.

PMID- 16583692
TI  - Two-dimensional reverse phase-reverse phase chromatography: A simple and robust
      platform for sensitive quantitative analysis of peptides by LC/MS. Hardware
      design.
AB  - We have revised current two-dimensional RP-RP approaches and developed a new
      robust 2-D RP-RP platform. This platform was implemented on an Agilent 1100 2-D
      liquid chromatography system and is based on high pressure switching between two
      high-resolution RP columns. An independent binary gradient was implemented for
      each dimension. The powerful combination of dual analytical columns with
      independent gradient elution achieves high analyte purity, effectively eliminates
      matrix effects, and maximizes MS sensitivity in Q1 SIM comparable to the
      sensitivity enhancements of MS/MS-based methods. Implementation of dual
      simultaneous gradient profiles (overlapped gradients) reduces 2-D method run-time
      to the scale of 1-D method run-times. This robust and sensitive approach is
      particularly suitable for hydrophobic peptides and small proteins and can be used
      as a routine standard technique for enhanced on-line peptide purification coupled
      with mass spectrometric detection.

PMID- 16583693
TI  - Chemometric evaluation of relationships between retention and physicochemical
      parameters in terms of multidimensional liquid chromatography of peptides.
AB  - Statistical evaluation of relationships between chromatographic retention and
      physicochemical descriptors of peptides was performed. The relationships
      describing retention were derived for a set of 98 structurally diversified
      peptides chromatographed on HPLC columns using acetonitrile and water with the
      addition of 0.1% trifluoroacetic acid as the mobile phase. It was found with the
      aid of multivariate principal component analysis (PCA) and factor analysis that
      the retention contributions of the amino acids comprising the individual peptide
      and the physicochemical parameters describing the bulkiness properties of
      peptides have the greatest influence on the retention of peptides, independent of
      the stationary phase used. Retention data were determined on six
      physicochemically different HPLC columns with the aid of experiments performed
      with various gradient times and column temperatures. Moreover, PCA permitted
      differentiation of the RP-HPLC columns used in terms of their similarities and
      dissimilarities in respect of peptide separations.

PMID- 16583694
TI  - Two-dimensional and serial column reversed-phase separation of phenolic
      antioxidants on octadecyl-, polyethyleneglycol-, and pentafluorophenylpropyl
      silica columns.
AB  - The separation selectivity of octadecyl-silica (C18) and of bonded
      pentafluorophenylpropyl-silica (F5) and PEG-silica columns was compared for
      natural phenolic antioxidants. The separation selectivities for phenolic
      antioxidants on C18 and F5 columns are strongly correlated, but low selectivity
      correlation indicating strong differences in the retention mechanism was observed
      between the C18 and PEG columns. Hence, the combination of a C18 and a PEG column
      is useful for separation of phenolic antioxidants that are not fully separated on
      single columns. Two-dimensional comprehensive liquid chromatography using a short
      PEG-silica column in the first dimension and a conventional C18-silica in the
      second dimension has the advantage of on-column focusing of the fractions
      transferred onto the C18 column in the second dimension, as a weaker mobile phase
      is used in the first dimension than in the second dimension. However, a stop-flow
      set-up in the first dimension system is necessary after the transfer of each
      fraction to the second dimension. Peak capacity is considerably larger but the
      separation time is much longer than with serially coupled PEG and C18 columns,
      which were employed for separation of beer and hop extract samples in connection
      with coulometric detection.

PMID- 16583695
TI  - Determination of beef tallow in lard through a multidimensional off-line non
      aqueous reversed phase-argentation LC method coupled to mass spectrometry.
AB  - The presence of tallow in lard is not easy to determine, due to the similarity of
      the composition of these two animal fats, which differ mainly in the distribution
      of fatty acids (FA) in the three positions of the glycerol molecule. The
      determination of the composition of the triacylglycerol (TAG) fraction of lard,
      tallow, and their mixtures was investigated by HPLC in combination with
      atmospheric pressure chemical ionization mass spectrometry (APCI-MS). The
      presence of tallow in lard was determined through the study of the sn-POP/sn-PPO
      ratio by multidimensional HPLC. The off-line bidimensional system was attained
      through the coupling of non-aqueous reversed phase (NARP)-HPLC and silver ion
      (Ag)-HPLC. The primary column eluate was fractionated and the fraction containing
      POP/PPO isomers was injected onto the secondary column, allowing the separation
      of positional isomers, unresolved in the first dimension. Peak assignment was
      carried out by combining retention data with APCI-MS spectral information. The
      fatty acid distribution along the glycerol backbone, determined by Ag-HPLC, was
      confirmed through diglyceride ion ratios derived from APCI-MS analysis. Method
      validation was carried out in preliminary applications on standard TAGs. The
      analytical results obtained show that even a 5% addition of tallow to lard
      modifies the distribution of positional isomers.

PMID- 16583697
TI  - Short communication controlling LC-SPE-NMR systems.
AB  - There are several stages of the LC-SPE-NMR process that should be monitored
      closely to ensure an efficient isolation and concentration of the target analyte,
      for instance analyte break-through and compound transfer from the LC-SPE to the
      NMR probe. In this study, analyte break-through monitoring was performed with a
      UV detector and a mass spectrometer placed after the SPE unit. Easy break-through
      was a problem when attempting multiple trapping of various compounds using C18
      SPE cartridges with the original commercial system. However, on lowering the flow
      rate over the SPE system and using SPE cartridges packed with porous carbon, the
      number of trappings possible increased five-fold. To increase control over the on
      line SPE-NMR transfer, a gradient pump-UV system was used to elute compounds
      trapped on an SPE to an NMR probe. The analyte band was placed in the active
      volume of the probe by a stop-flow mechanism. The modified LC-SPE system was also
      coupled with off-line NMR analysis for determination of a degradation product of
      the insecticide monuron, present in the low ppm range.

PMID- 16583696
TI  - Determination and removal of impurities in 2-D LC-MS of peptides.
AB  - Problems occurring during operation of a 2-D LC-MS system for separation and
      identification of neuropeptides, such as contamination of the used salts and
      column bleed, are described. When using polysulfoethyl aspartamide, which is
      widely used as a strong cation exchange stationary phase in the first dimension,
      interfering peaks were observed in the second-dimension reversed-phase
      chromatograms. The observed peaks, found to be caused by column bleeding, had
      abundance above the threshold value and influenced the quality of the analyses.
      The origin of the peaks was verified and appropriate measures are proposed.
      Additionally, peaks caused by polyethylene glycols (PEGs), covering approximately
      5 min of feasible chromatographic time in every fraction, were observed. The
      commercial ammonium formate salts used to prepare the first-dimension mobile
      phase were found to contain PEG impurities, and in subsequent work the salt
      solutions were prepared from formic acid and ammonia to avoid any additional
      contaminations.

PMID- 16583698
TI  - [Generation and analysis of novel mutations of the trithorax-like gene in
      Drosophila melanogaster].
AB  - The Trithorax-like (Trl) gene of Drosophila melanogaster encodes the
      multifunctional GAGA factor. The expression of Trl is known to depend on numerous
      factors, such as the organ, the tissue, the ontogenetic stage, and the ambient
      temperature. Apparently, this expression is controlled by a complex system of
      regulatory elements, which so far has been scarcely studied. Our preliminary
      results indicate that the second intron of the Trl gene bears functionally
      significant elements. To test this assumption, we generated 23 novel alleles of
      the gene via P-induced male recombination and analyzed them cytogenetically. Of
      these mutations, 13 (recessive lethals) are deletions, disrupting the coding gene
      region. Ten mutations (seven deletions and three duplications) remove parts of
      the second Trl intron only. Some of these mutant stocks exhibit lower viability
      at different temperatures. These results suggest that the second intron region
      harbors functionally significant elements. The deletion mapping results verified
      the localization of the Trl gene in the 70F1-2 region.

PMID- 16583699
TI  - [Ambivalent bacteriophages of different species active on Escherichia coli K12
      and Salmonella sps. strains].
AB  - A study was made of several bacteriophages (including phages U2 and LB related to
      T-even phages of Escherichia coli) that grow both on E. coli K12 and on some
      Salmonella strains. Such phages were termed ambivalent. T-even ambivalent phages
      (U2 and LB) are rare and have a limited number of hosts among Salmonella strains.
      U2 and LB are similar to canonical E. coli-specific T-even phages in
      morphological type and size of the phage particle and in reaction with specific
      anti-T4 serum. Phages U2 and LB have identical sets of structural proteins, some
      of which are similar in size to structural proteins of phages T2 and T4. DNA
      restriction patterns of phages U2 and LB differ from each other and from those of
      T2 and T4. Still, DNAs of all four phages have considerable homology.
      Unexpectedly, phages U2 and LB grown on Salmonella bungori were unstable during
      centrifugation in a CsCl gradient. Ambivalent bacteriophages were found in
      species other than T-even phages and were similar in morphotype to lambdoid and
      other E. coli phages. One of the ambivalent phages was highly similar to well
      known Felix01, which is specific for Salmonella. Ambivalent phages can be used to
      develop a new set for phage typing in Salmonella. An obvious advantage is that
      ambivalent phages can be reproduced in the E. coli K12 laboratory strain, which
      does not produce active temperate phages. Consequently, the resulting typing
      phage preparation is devoid of an admixture of temperate phages, which are common
      in Salmonella. The presence of temperate phages in phage-typing preparations may
      cause false-positive results in identifying specific Salmonella strains isolated
      from the environment or salmonellosis patients. Ambivalent phages are potentially
      useful for phage therapy and prevention of salmonellosis in humans and animals.

PMID- 16583701
TI  - [Transposition of the hobo element in Drosophila melanogaster somatic cells].
AB  - Somatic mutation and recombination test on wing cells of Drosophila melanogaster
      showed that the recombination frequency in the somatic tissues of strains studied
      correlated with the presence of a full-length copy of the hobo transposable
      element in the genome. Transposition of hobo in somatic tissue cells at a
      frequency 3.5 x 10-2 per site per X chromosome was shown by fluorescence in situ
      hybridization with salivary gland polytene chromosomes of larvae of one of the D.
      melanogaster strains having a full-length hobo copy.

PMID- 16583700
TI  - [The mechanism of the effect of apterous56f mutation on the reproductive function
      of Drosophila melanogaster].
AB  - The effects of L-dihydroxyphenylalanine (L-DOPA) and 20-hydroxyecdysone (20E)
      were studied with respect to the content of dopamine (DA), intensity of the
      juvenile hormone (JH) degradation, and fecundity of the wildtype flies (Canton S)
      and JH-deficient apterous56f mutants (in young females, carrying this mutation,
      the levels of DA and 20E production were strongly increased). Fly feeding with L
      DOPA proved to increase the level of DA in a dose-dependent manner and reduce JH
      degradation in 2-day-old females of both strains. Feeding with 20E produced the
      same effect. Treating the wild-type flies with 2.5 mg L-DOPA caused a 24-h delay
      in beginning of oviposition and reduction in fecundity throughout the experiment.
      An L-DOPA dose of 1 mg caused no such changes. An experimental increase in 20E
      titer led to reduced fecundity of the wild-type flies, though no delay in
      oviposition was observed. In mutant flies, an increase in DA and 20E levels
      accelerated beginning of oviposition and increased fecundity of young females,
      though the latter parameter was reduced in mature individuals. Thus, an increase
      in endogenous DA and 20E characteristic of young apterous56f females is assumed
      to be a compensatory response that leads to a higher JH titer and induction of
      vitellogenesis.

PMID- 16583702
TI  - [A modifier of the Bg element of the Bg-rbg transposable element system of
      maize].
AB  - A modifier of the Bg autonomous element of the Bg-rbg system of transposable
      elements has been found in the genotype of the inbred maize strain 346. In the
      presence of this modifier (termed Mbg), the frequency of reversion of mutable
      allele o2-lf in combination with the Bg-lf element increases by 7-24 times. An
      increase in the Mbg dosage by three times increases the o2-lf reversion frequency
      by a factor of about two. The presence of Mbg and Bg-lf in the same genotype
      before meiosis is necessary for the expression of the Mbg modifying effect. The
      possible nature and mechanism of action of the novel modifier are discussed.

PMID- 16583703
TI  - [Variation in evolutionary unstable regions of the chloroplast genome in plants
      obtained in anther culture of dihaploid wheat lines].
AB  - In dihaploid wheats, two evolutionarily unstable regions of the chloroplast
      genome were examined. These regions include the following genes, changes in which
      could be associated with albinism in anther culture: rbcL, encoding the large
      Rubisco subunit; psaA, encoding p700 apoprotein Ia; petA, encoding cytochrome f;
      atpB and atpE, encoding respectively beta and epsilon subunits of the CF1 ATPase
      complex; trnE, encoding glutamine tRNA; and cemA, encoding a cell membrane
      protein. Using PCR, we have shown that atpB was the gene most often not detected
      in the lines examined. These results suggest that regeneration of albino plants
      is accompanied by a deletion of a chloroplast DNA region harboring this gene.

PMID- 16583704
TI  - [Cytogenetic analysis of alloplasmic recombinant lines (H. vulgare)-T. aestivum
      with unstable fertility and viability].
AB  - Comparative cytogenetic analysis was performed with four alloplasmic recombinant
      (Hordeum vulgare)-Triticum aestivum lines differing in morphological traits,
      number of seeds per spike, and seed plumpness. None of the lines displayed
      introgression of the barley genetic material: the karyotypes included only common
      wheat chromosomes. Two lines, 79(B) and 79(D), were cytogenetically stable.
      Plants of lines 79(A) and 79(C) displayed a high frequency of unbalanced
      chromosome aberrations, including dicentric and polycentric chromosomes, terminal
      deletions varying in size, acentric fragments, and multiple unidentifiable
      translocations. Previous studies of the mitochondrial genome showed that the two
      cytologically unstable lines, which were also unstable in fertility and
      viability, are characterized by heteroplasmy at the mitochondrial 18S-5S locus
      (simultaneous presence of barley and wheat fragments). Stable lines 79(B) and
      79(D) with normal fertility contained only wheat mitochondrial markers. It was
      assumed that the substantial instability of the nuclear genome in lines 79(C) and
      79(A) was a result of nuclear-cytoplasmic incompatibility and was associated with
      heteroplasmy, while elimination or considerable reduction of barley material in
      the mitochondrial genome stabilized the nuclear genome of lines 79(B) and 79(D).
      In turn, the instability of the nuclear genome was responsible for a decrease in
      viability and fertility of plants.

PMID- 16583705
TI  - [Sugar beet (Beta vulgaris L.) morphogenesis in vitro: effects of phytohormone
      type and concentration in the culture medium, type of explants, and plant
      genotype on shoot regeneration frequency].
AB  - In vitro regeneration techniques have been optimized for seven strains and
      cultivars of sugar beet (Beta vulgaris L.) bred in Russia. The frequency of shoot
      regeneration from somatic cells and tissues of sugar beet varies from 10 to 97%
      depending on the explant type, culture-medium composition, and genotype. The in
      vitro regeneration potential has been estimated in plants with different
      genotypes. The effect of medium composition (phytohormones and carbohydrates) on
      the frequency of the formation of a morphogenic callus competent for plant
      regeneration has been determined. The effect of the types and concentrations of
      various cytokines (zeatin, kinetin, and 6-benzylaminopurine) on direct shoot
      regeneration from cotyledon nodes has been estimated. The culture-medium
      composition has been optimized for direct shoot regeneration from petioles. The
      effects of different concentrations of abscisic acid on the frequency of shoot
      regeneration from a morphogenic callus has been studied. Micropropagation has
      been used to obtain petiole explants and reproduce the shoots obtained by direct
      regeneration from cotyledon nodes, petioles, and calluses. Improved shoot
      regeneration methods can be used for both agrobacterial and bioballistic genetic
      transformation of the sugar beet genotypes studied.

PMID- 16583706
TI  - [Study of morphological and symbiotic traits during the ontogeny of supernodular
      and hypernodular pea mutants].
AB  - Morphological (plant height and vegetative biomass amount) and symbiotic (number
      of nodules and nitrogenase activity) traits of six symbiotic pea mutants and the
      original cultivar Rondo were studied at different vegetation periods. Of the
      mutants studied, one (K10a) was supemodular and the remaining five (K1a, K2a,
      K5a, K7a, and K27a) were hypemodular. Essential distinctions in the absolute
      values and time course of the changes in individual morphological and symbiotic
      traits of different pea mutants were demonstrated. The supemodular type is
      inferior to the original cultivar in plant height and production of vegetative
      biomass, but exceeds it in nodulation and nitrogen fixation. The hypemodular
      mutants either surpass the original cultivar with respect to the production
      capacity or display similar results. The symbiotic traits-number of nodules and
      nitrogen fixation activity--of these mutants are higher compared with the Rondo
      cultivar. The mutants K1a, K2a, and K27a were demonstrated to be useful in
      breeding pea for an increase in nitrogen fixation.

PMID- 16583707
TI  - Genetic differences between populations and habitats in Lamium purpureum plastic
      response to conspecific density.
AB  - Plants from Open and Shade habitats in two natural populations (Vrsac and Avala)
      were grown in two densities (High and Low). As expected, density had significant
      effect on most of measured traits and that effect was concordant with Shade
      avoidance syndrome predictions. Genetic differences between populations both in
      mean trait values and in plastic responses to density were also detected. Number
      of leaves and flowers showed plasticity in Avala population only, while shoot
      weight was plastic in both populations but with greater plasticity in Avala
      population. Differences between habitats for plant height and number of
      internodes were present in Vrsac population only. Habitat difference in response
      to density was revealed for seed weight and it was due to lack of response in
      plants originated from Shade habitat in Vrsac population. This study showed that
      not only populations, but also subpopulations occupying different habitats can
      differ genetically in their plastic response to density, and that between habitat
      differences can be population-specific.

PMID- 16583708
TI  - [Variation of cytochrome b gene in sympatric chars from Kronotsky Lake (Kamchatka
      oblast)].
AB  - In previously identified sympatric char forms (species) from Kronotsky Lake
      (Kamchatka Peninsula) and a number of other chars from the genus Salvelinus,
      nucleotide sequences of the mtDNA cytochrome b gene were determined and
      phylogenetic analysis of these forms was performed. The divergence of the
      cytochrome b gene in the Kronotsky char group (0.48%) coincided with the
      interpopulation difference estimates in northern Dolly Varden, which indicates a
      relatively recent divergence of the chars from Kronotsky Lake. Haplotypes of each
      form of the Kronotsky Lake chars are divided into two groups, which belonged to
      two different phylogenetic mtDNA lineages of northern Dolly Varden from Chukotka
      and Kamchatka. The formation of the Kronotsky char forms proved to be unrelated
      to the observed variability of the mtDNA cytochrome b gene.

PMID- 16583709
TI  - [Variation in morphometric and genetic characteristics of stellate sturgeon
      juveniles raised at different densities].
AB  - Genetic and size/weight characteristics of stellate sturgeon juveniles were
      examined under standard and twice lower than standard densities. Viability,
      growth rate, and variability of juveniles were higher at standard density.
      Individuals with different genotypes exhibited higher viability and faster growth
      at different densities, which was particularly pronounced in case of the PGM1
      locus. Despite the high phenotypic variability of sturgeon juveniles under
      standard conditions, its genetic component was higher at low density. It was
      concluded that low density conditions, which are closer to the natural ones,
      mediate maintenance of genetic variability.

PMID- 16583710
TI  - [Analysis of polymorphism at nine nuclear genome DNA loci in maris].
AB  - Population genetic survey of the indigenous populations of the Marii El Republic,
      represented by the two major ethnographic groups of Maris, Meadow (five samples
      from Morkinsk, Orshansk, Semursk, Sovetsk, and Zvenigovsk districts) and Mountain
      (one sample from Gornomariisk district) Maris, was carried out. All Mari groups
      were examined at nine polymorphic DNA loci of nuclear genome, VNTR(PAH) (N =
      422), STR(PAH) (N = 152), VNTR(ApoB) (N= 294), VNTR(DAT1) (N = 363), VNTR(eNOS)
      (N = 373), ACE (N = 412), IVS6aGATT (N = 513), D7S23(KM.19) (N = 494), and D7S8
      (N = 366). Allele and genotype frequency distribution patterns were obtained for
      individual samples and ethnographic groups, as well as for the ethnic group
      overall. In each of six Mari samples examined, the deficit of heterozygotes was
      observed, i.e., the mean observed heterozygosity was lower than the expected one.
      The indices of mean heterozygosity, Hs = 0.455, and interpopulation
      differentiation, FST = 0.0024, for the Mari gene pool were obtained using a set
      of DNA markers analyzed. Analysis of the genetic distances and between population
      differentiation (FST) showed that the main part of genetic diversity in Maris was
      determined by the differentiation between the populations of Meadow Maris. The
      contribution of the differences between the ethnographic groups of Mountain and
      Meadow Maris to the ethnic gene pool was small. It is suggested that the main
      role in the formation of the Mari gene pool is played by the geographic factor.

PMID- 16583711
TI  - [Identification of the proteins interacting with neuroprotective peptide humanin
      in a yeast two-hybrid system].
AB  - Humanine is a human neuroprotective peptide with a wide action spectrum. To
      analyze molecular mechanisms of humanin functioning, a search for proteins
      interacting with this peptide was conducted using yeast two-hybrid system.
      Screening of human fetal brain cDNA library identified seven proteins with
      different functions that specifically interacted with humanin.

PMID- 16583712
TI  - [Evaluation of salt tolerance in Nicotiana tabacum plants bearing an antisense
      suppressor of the proline dehydrogenase gene].
AB  - We studied the stress resistance of genetically modified (GM) tobacco plants
      bearing an antisense suppressor of the gene for proline dehydrogenase. Such
      plants are characterized by elevated proline content. The progeny of the
      transgenic plants were shown to have elevated salt tolerance.

PMID- 16583713
TI  - Spatial autocorrelation in two Iris pumila populations estimated on morphological
      data from natural clones and their samples grown in two different habitats.
AB  - Morphological data from two Iris pumila populations (measured on native clones,
      on their replants into the same habitat, and on their transplants into
      alternative habitat) were combined with native clones spatial position and
      spatial autocorrelations (SA) were calculated. Naturally growing I. pumila clones
      revealed significant SA that were positive on small distances and negative on
      medium ones in both open Hillock and shaded Woodland populations. No significant
      SA were detected when calculated with original clone positions, but with
      morphometric data from replants into the experimental plot in the same habitat.
      Some significant SA were, however, detected when morphometric data from
      transplants to alternative habitat were used. Detected SA on I. pumila clones
      were primarilly a consequence of spatial structuring of environmental factors but
      also, in lesser degree, a result of genetic spatial arrangements (most probably
      due to patterns of gene flow).

PMID- 16583714
TI  - Lost fundamentals in neurosciences--a call for discussion.

PMID- 16583715
TI  - The optimal use of triptans--sooner is better.

PMID- 16583716
TI  - Alzheimer's disease clinical trials: where are we now?

PMID- 16583717
TI  - Progress in clinical neurosciences: Canadian guidelines for the development of
      antidementia therapies: a conceptual summary.
AB  - The magnitude of the problems faced by an aging Canadian society has been clearly
      identified. Perhaps the single most important problem is the increasing incidence
      of dementia. Alzheimer's disease (AD) accounts for 50-60% of the dementias in
      later life within a spectrum of other contributing dementias. Regulatory approval
      has been given to Acetylcholinesterase inhibitors for the symptomatic treatment
      of mild to moderate AD, and conditional approval to memantine for the symptoms of
      moderate to severe AD. There has been no regulatory approval for the treatment of
      the degenerative dementias beyond AD. The very rapid progress in the past decade
      in biotechnology and in the molecular biology of the dementias is supporting a
      new generation of innovative treatment strategies that will more directly target
      the underlying disease pathogenic mechanisms. Such treatments will foreseeably
      include immunotherapies, anti-aggregants that may prevent misfolding and
      deposition of proteins, and neuroregenerative interventions. These Guidelines
      follow the 2nd Canadian Conference on the Development of Antidementia Therapies,
      held in 2004, which covered a range of design, methodological and ethical issues
      facing clinical researchers and regulatory authorities. They are intended to
      provide a common point of reference and guidance in Canada for therapeutic
      development of the dementias.

PMID- 16583718
TI  - Cardiac valvulopathy associated with pergolide use.
AB  - OBJECTIVE: To review the risk of pergolide associated cardiac valvulopathy in
      patients with Parkinson's disease. DATA SOURCES: MEDLINE, Embase, and the
      Cochrane Library. Reference lists were reviewed and librarians were consulted to
      identify additional trials. STUDY SELECTION: All studies and case reports in the
      English literature on pergolide and cardiac valvulopathy. DATA EXTRACTION:
      Demographics of patients, study duration, dose and duration of pergolide use,
      echocardiogram results, length of follow-up, and clinical outcome. RESULTS:
      Twenty-two published articles were identified. There were no randomized
      controlled trials. Follow-up time varied between a few months and four years.
      Three case reports and four studies (three case control and one observational)
      assessed 246 patients. Evidence for valvulopathy was found in all studies.
      Variable methods were used to assess the degree of valvular regurgitation making
      comparisons between studies difficult. Little clinical correlation is available
      for echocardiogram results. Variable improvement was shown in the few patients in
      whom the drug was stopped. There is insufficient data to determine whether dose
      and duration or other comorbities have an effect on the risk of developing
      cardiac valvulopathy. CONCLUSION: Pergolide therapy is associated with an
      increased risk of developing cardiac valvulopathy but the true incidence and
      importance of this remains unknown. Further prospective studies are needed with
      standardized assessments of echocardiograms.

PMID- 16583719
TI  - Blood pressure as an independent prognostic factor in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Blood pressure is elevated in most patients during acute
      ischemic stroke, but the prognostic significance of this is unclear as the
      current data yield conflicting results. METHODS: Admission blood pressure from
      the 1281 patients in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) was
      analyzed for prognostic significance as well as the risk of hemorrhagic
      transformation. We also examined weighted-average blood pressure over seven days,
      and the impact of a 30% change in blood pressure in 24 hours. Patients with
      severe hypertension were excluded from the TOAST trial. RESULTS: Increasing
      systolic blood pressure (SBP) on admission, but not diastolic (DBP) or mean
      arterial pressure (MAP) was predictive of poor outcome, but this effect was not
      significant after adjustment for other know prognostic factors. Increasing
      weighted-average SBP and MAP over seven days were predictive for poor outcome,
      but a 30% change in blood pressure over 24 hours was not. CONCLUSIONS: Admission
      blood pressure is not an independent prognostic factor in acute ischemic stroke,
      but the weighted-average of SBP and MAP over seven days probably does have
      predictive value with higher values having a worse prognosis. A prospective trial
      of blood pressure control during acute stroke is needed.

PMID- 16583720
TI  - Stroke recurrence and its prevention in patients with patent foramen ovale.
AB  - BACKGROUND: It is unclear whether medical or invasive (surgical or catheter
      interventional) treatment is preferable to prevent recurrence of cerebral
      ischemia in patients with patent foramen ovale (PFO) as the suspected cause of
      stroke and what the role of concomitant risk factors is in stroke recurrence.
      METHODS: Over a period of ten years, 124 patients (mean age 51 +/- 15 years) with
      cryptogenic cerebral ischemia and PFO were included into the study and
      prospectively followed over a mean of 52 +/- 32 months. Of these, 83 were treated
      medically, 34 underwent transcatheter closure, and seven had surgical closure of
      the foramen. Of the medically treated patients, 11 stopped medication during
      follow-up. Recurrent ischemic events and risk factors for recurrence were
      analyzed. RESULTS: Annual stroke recurrence rates were generally low and
      comparable in catheter and medically treated patients, and in patients who had
      stopped medication (2.9%/2.1%2.2%/year). Patients suffering from recurrence after
      transcatheter closure (n = 2) both had residual shunts. No stroke recurrence was
      observed in the few surgically treated patients. An atrial septal aneurysm was
      not a predictor of recurrent or multiple strokes (p > 0.05, OR = 0.31, and OR =
      0.74). Large shunts and a history of previous ischemic events were considerably
      more frequent in patients with recurrent strokes (p < 0.05, OR = 5.0, and OR =
      4.4). Pulmonary embolism and case fatality rates were significantly higher in
      patients with stroke recurrence (p < 0.001, and p < 0.01). CONCLUSIONS: The
      absolute risk of recurrent cerebrovascular events in patients with PFO receiving
      medical or catheter interventional therapy is low. The small group of untreated
      patients had a comparably low rate of stroke recurrences. Previous ischemic
      events and shunt size were risk factors in this observational study. Given
      conflicting findings across multiple studies, enrollment into a randomized
      controlled trial would be the optimal choice.

PMID- 16583721
TI  - Discharge destination from acute care after traumatic brain injury.
AB  - OBJECTIVE: To identify the impact of private insurance coverage on discharge
      disposition after a traumatic brain injury (TBI) using injury in a motor vehicle
      accident (MVA) as a proxy for private insurance, controlling for age and severity
      of injury. METHOD: Cross-sectional study. PATIENTS: Patients with TBI discharged
      between 1993-1994 and 2000-2001 (n = 9,703). MAIN OUTCOME MEASURE: Discharge
      destination from acute care; controlled odds ratio (OR) and confidence interval
      (CI) for type of injury. RESULTS: Type of injury, age, and length of stay are
      significantly associated with discharge destination. However, the motor vehicle
      accident patients are 56% more likely to be discharged to home with support
      services than patients with similar injuries from falls. CONCLUSION: Even in a
      system with universal coverage, availability of private insurance type is a
      potential independent determinant of post-acute care services. More research is
      required to determine the effect this relationship has on the cost and outcomes
      of care for TBI patients.

PMID- 16583723
TI  - MR angiography compared to conventional selective angiography in acute stroke.
AB  - BACKGROUND AND PURPOSE: Accuracy of intracranial magnetic resonance angiography
      (MRA) and reliability of interpretation are not well established compared to
      conventional selective catheter angiography. The purpose of this study was to
      determine the accuracy of MRA in evaluation of intracranial vessels in acute
      stroke and transient ischemic attack (TIA) patients METHODS: Twenty-nine patients
      (seven females, 22 males; median age 53) with acute stroke or TIA were enrolled
      into the study. All patients underwent both MRA using a 3 T clinical magnet and
      conventional angiography within 48 hours. Median time between MRA and angiography
      was 263 minutes. Conventional angiography preceded MRA in 15 cases. Fourteen
      patients received thrombolysis during MRA or angiography. National Institutes of
      Health Stroke Scale scores were obtained prior to the MR exam. One
      neuroradiologist rated all conventional angiograms, which were used as gold
      standard. Five observers, blinded to conventional angiography results and all
      clinical information except symptom side, rated the MR angiograms. Kappa
      statistics were used to assess reliability; contingency tables were used to
      assess accuracy of non-enhanced and enhanced MRA. RESULTS: Two hundred and fifty
      two intracranial vessels were assessed. Agreement between raters was good for
      both non-enhanced (kappa = 0.50) and gadolinium-enhanced (kappa = 0.46) images.
      There were a total of 26 vessels occluded by DSA. Overall, the non-enhanced MRA
      showed sensitivity of 84.2% (95% CI 60.4-96.6) and specificity of 84.6% (95% CI
      78.6-89.4). The enhanced MRA showed sensitivity of 69.2 (95% CI 38.6-90.9) and
      specificity of 73.6 (95% CI 65.5-80.7). CONCLUSIONS: Magnetic resonance
      angiography is a good non-invasive screening tool for assessing intracranial
      vessel status in acute ischemic stroke. Angiography remains the gold standard for
      definitive assessment of the intracranial circulation.

PMID- 16583722
TI  - Referrals for movement disorder surgery: under-representation of females and
      reasons for refusal.
AB  - OBJECTIVE: Referral of movement disorder patients for deep brain stimulation
      surgery was examined to determine whether referred patients were representative
      of gender proportions in our population, and reasons why patients do not proceed
      to surgery. METHODS: Demographic information on referrals to the surgical program
      was retrospectively reviewed from our database and from a detailed chart review.
      RESULTS: Although almost equal numbers of movement disorder patients are male and
      female, of the 91 patients referred for surgery, only 31% were female. Sixty-one
      percent of referred patients did not undergo surgery. Of these, the majority were
      denied for medical reasons, including cognitive decline (21%), psychiatric
      concerns (5%) and neurological reasons (42%). CONCLUSIONS: Almost one-third of
      patients referred for movement disorder surgery were denied for medical reasons.
      This underscores the importance of evaluation of all potential patients by a
      multidisiplinary team to fully assess suitablity for stereotactic surgery.
      Interestingly, women were under-represented in those referred. In order that all
      appropriate patients have the opportunity to consider surgery, education of both
      physicians and patients, and different strategies to approach females regarding
      surgery may allow more patients to benefit from this treatment.

PMID- 16583724
TI  - Motor and occipital cortex excitability in migraine patients.
AB  - OBJECTIVE: We evaluated motor and occipital cortex excitability in migraine
      patients using transcranial magnetic stimulation. METHODS: In this study, we
      included 15 migraine patients with aura (MwA), 15 patients without aura (MwoA)
      between attacks, and 31 normal healthy controls. Motor thresholds at rest,
      amplitudes of motor evoked potentials, central motor conduction time and cortical
      silent period were measured by stimulation of the motor cortex by using 13.5 cm
      circular coil and recording from abductor digiti minimi muscle. Additionally,
      phosphene production and the threshold of phosphene production was determined by
      stimulation of the visual cortex with the same coil. RESULTS: No significant
      differences were observed between the groups with respect to the motor
      thresholds, Motor evoked potential max/compound muscle action potential max
      (MEPmax/Mmax) amplitudes, central motor conduction times and duration of cortical
      silent period. Although not statistically significant, the proportion of the
      migraineurs with phosphene generation (90%) was found to be higher than that of
      normal controls (71%). Phosphene threshold levels in migraine patients, however,
      were significantly lower than those of the controls with MwA patients having the
      lowest levels. CONCLUSION: Our findings indicate that the occipital cortex, but
      not the motor cortex, is hyperexcitable in migraine patients.

PMID- 16583725
TI  - CACNA1A mutation in a EA-2 patient responsive to acetazolamide and valproic acid.
AB  - BACKGROUND: Episodic ataxia type-2 (EA-2) is an autosomal dominant neurological
      disorder that has been shown to result from mutations in the CACNA1A gene
      encoding the P/Q-type calcium channel. Affected individuals experience episodes
      of cerebellar ataxia usually associated with migraine symptoms, interictal
      nystagmus, mild residual and in some cases a progressive cerebellar
      incoordination and respond to acetazolamide treatment. We identified a patient
      with a positive family history for episodic ataxia, who was originally diagnosed
      with epilepsy and treated with valproic acid. Subsequent examination revealed
      that the symptoms were consistent with a diagnosis of EA-2. The patient responded
      positively to a combination of acetazolamide and valproic acid. Molecular genetic
      analysis of the CACNA1A gene was performed in order to confirm a diagnosis of EA
      2. METHODS: The CACNA1A gene was evaluated for mutations using single strand
      conformational polymorphism analysis and direct DNA sequencing. Allele specific
      oligo hybridization was used to confirm that the mutation was segregating with
      only affected family members and was not present in the control group. RESULTS:
      In this study we identified a new missense mutation in exon 12 of the CACNA1A
      gene from a patient with EA-2 whose symptoms could be controlled with a
      combination of acetazolamide and valproic acid. This G to A transition changes a
      highly conserved glutamic acid residue to a lysine residue in domain II S2 of the
      P/Q-type calcium channel alpha1A subunit. CONCLUSIONS: The use of valproic acid
      in treating patients with EA-2 is not well documented. Here we describe a patient
      with a novel mutation in the CACNA1A gene who responded positively to a
      combination of acetazolamide and valproic acid.

PMID- 16583726
TI  - Pain free efficacy of sumatriptan in the early treatment of migraine.
AB  - BACKGROUND: There is evidence that headache response rates may be higher if
      triptans are used early when a migraine attack is still mild, as compared to when
      it is treated after pain has reached moderate or severe intensity. METHODS: In
      this randomized, double blind, placebo controlled, parallel group clinical trial,
      361 patients took either placebo, sumatriptan 50 mg, or sumatriptan 100 mg in a
      single attack study. The primary outcome measure was pain-free status at two
      hours. RESULTS: In the intention to treat group, two hour pain free rates were
      16%, 40%, and 50% in the placebo group, sumatriptan 50 mg group, and the
      sumatriptan 100 mg group respectively (p < 0.001, active treatment groups vs.
      placebo). CONCLUSIONS: Both sumatriptan 50 mg and 100 mg were significantly
      superior to placebo for the pain-free end point at two hours. The pain-free
      response rates in this trial where sumatriptan was taken while the headache was
      still mild were generally higher than in older clinical trials where headache was
      treated after reaching a moderate or severe intensity.

PMID- 16583727
TI  - Validation of a quality-of-life questionnaire for patients with pituitary
      adenoma.
AB  - BACKGROUND: The purpose of this study was to develop and validate a self
      administered questionnaire to measure the health-related quality of life of
      patients with pituitary adenoma. METHODS: A patient-centred iterative process,
      involving a literature review and focus group interviews with 84 patients, was
      used to develop a preliminary 106-item questionnaire and to validate it. The
      final questionnaire comprised the 30 most important items chosen by 20 patients
      and 17 items considered important by health care professionals. For assessment of
      its validity and reliability, 55 patients were asked to complete the final
      questionnaire, RAND-36, FACT- G/FACT-Br, and Karnofsky Performance Scale (KPS).
      Concurrent validity of the results of our questionnaire with those of the other
      instruments was assessed with Pearson correlation coefficients. Known-group
      validity for the scores of extreme groups was assessed with a Student's t test.
      Test-retest reliability was determined with Pearson correlation coefficients and
      a Student's t test for two sets of scores obtained one month apart. RESULTS:
      Forty-seven (85.5%) of the 55 questionnaires were completed. Our questionnaire
      was well correlated with the RAND-36, the FACT-Br, the FACT-G, and the KPS in the
      general health domain, but not with the KPS overall. Extreme groups (n = 20) were
      significantly different. Test-retest reliability (n = 24) was 0.88, and scores
      one month apart were not significantly different. CONCLUSION: Our patient-centred
      health-related quality of life questionnaire developed for patients with
      pituitary adenoma had good validity and reliability. This questionnaire could be
      used as a patient-centred outcome measure in clinical trials and for assessment
      of disease progression.

PMID- 16583728
TI  - MR-pathological comparison in F98-Fischer glioma model using a human gantry.
AB  - OBJECT: This study reports our findings in assessing in vivo tumour growth with
      magnetic resonance imaging using a commercial magnet and antenna in F98 implanted
      Fischer rats. A comparison of T1 gadolinium-enhanced coronal MR scans and
      pathology specimens in corresponding animals was accomplished. METHODS: One rat
      was used in serial experiments to establish adequate imaging parameters.
      Afterward, 12 animals implanted with F98 cells underwent a MR study following
      intervals spanning five, ten, 15 and 20 days on a 1.5T human Siemens. Using a
      small loop antenna, a coronal T1 weighted MRI scan with Gadolinium was performed.
      Images were analyzed and volumes of enhancing tumour were calculated. The animals
      were sacrificed after the imaging procedure and brain were harvested and
      processed in pathology. Pathology specimens and MR images were analyzed using
      image processing software. One hematoxylin + eosin (H&E) slide per specimen was
      compared to the corresponding MR slice depicting the largest area of enhancement.
      RESULTS: The MR enhancement areas obtained were 2.18 mm2, 8.25 mm2, 21.6 mm2 and
      23.17 mm2 at five, ten, 15 and 20 days. Tumour margin measurements on pathologic
      samples produced areas of 0.29 mm2, 4.43 mm2, 8.3 mm2, and 12.9 mm2 at five, ten,
      15 and 20 days respectively. CONCLUSION: The T1-enhancing images constantly
      overestimated the tumour bulk on H&E. This phenomenon is explained by enhancement
      of the brain around tumour, the extra-axial tumour growth, and a shrinking factor
      of 17% related to the fixation process. Nonetheless, the radiological tumour
      growth paralleled the histological samples. This technology is thus suitable to
      follow tumour growth in F98 implanted rats.

PMID- 16583729
TI  - A patient with neurosarcoidosis.

PMID- 16583730
TI  - Magnetic resonance imaging of Asians with multiple sclerosis was similar to that
      of the West.
AB  - Magnetic resonance imaging (MRI) of the brain is the most important paraclinical
      diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with
      MS is not well defined. We retrospectively surveyed the first brain and spinal
      cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven
      regions throughout Asia to define the MRI changes among Asians with MS. There
      were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom
      had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted
      images, mostly asymptomatic. Almost all the lesions were in the white matter,
      particularly in the juxtacortical, deep and periventricular white matter. A third
      of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were
      more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five
      percent of the spinal cord lesions were in cervical and thoracic regions, 34%
      enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3
      vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal
      MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and
      classical groups of patients were similar in appearance and distribution, except
      that the optic-spinal MS patients have fewer brain but longer and more severe
      spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian
      patients with MS was similar to that of the West, although, in this study, Asian
      MS patients had larger spinal cord lesions.

PMID- 16583731
TI  - Midline cerebellar medulloblastoma in a seventy-one-year-old patient.
AB  - BACKGROUND: Medulloblastoma is the most common malignant central nervous system
      tumour in children but, in contrast, quite rare in adults. Hemispheric, rather
      than midline, cerebellar medulloblastomas are more common in older children and
      adults. We present the unusual case of a 71-year-old man who presented with a
      fourth ventricular mass that proved to be a medulloblastoma. METHODS: A 71-year
      old man presented with progressive balance problems, slurred speech and double
      vision. A CT scan of the brain revealed a hyperattenuating, partially calcified,
      avidly enhancing mass within the fourth ventricle. Diffusion weighted MRI showed
      restricted diffusion within the mass. The patient underwent a midline
      suboccipital craniotomy and a subtotal resection was achieved. RESULTS:
      Histological examination showed a densely cellular neoplasm composed of small
      cells with a tendency towards neuroblastic rosette formation. Most cells were
      strongly positive for neuron-specific enolase and synaptophysin.
      Ultrastructurally, tumour cells showed evidence of neuronal differentiation.
      These findings were consistent with a classical medulloblastoma. CONCLUSION:
      Adult medulloblastoma should be considered in the differential diagnosis of a
      partially calcified hyperattenuating mass within the fourth ventricle.

PMID- 16583732
TI  - BiPAP in early guillain-barre syndrome may fail.
AB  - BACKGROUND: Non-invasive mechanical ventilation (BiPAP) has been introduced for
      use in neuromuscular respiratory disease such as amyotrophic lateral sclerosis
      and myasthenia gravis. There is no experience in Guillain-Barre syndrome.
      METHODS: We describe for the first time the use of BiPAP to assist in the work of
      breathing in two consecutive patients with progressing Guillain-Barre syndrome
      (GBS) and marginal pulmonary function. RESULTS: Our initial attempts to use BiPAP
      in GBS and early neuromuscular respiratory failure were totally unsuccessful.
      There was marked initial improvement; however, emergency intubation was needed in
      both patients, one of which became acutely cyanotic. CONCLUSIONS: Until more
      experience is available, we strongly warn against using BiPAP in deteriorating
      patients with GBS.

PMID- 16583733
TI  - Utility of Ictal SPECT in the presurgical evaluation of Rasmussen's encephalitis.
AB  - BACKGROUND: Rasmussen's encephalitis is a progressive disease characterized by
      severe progressive neurological and cognitive deficits. It is a difficult
      condition to treat with conventional medical treatment and requires, in most of
      the cases, surgical intervention. METHODS: We present the case of a patient with
      Rasmussen's encephalitis who presented with epilepsia partialis continua, who did
      not respond to antiepileptic treatment and was evaluated for possible surgical
      intervention. RESULTS: The electroencephalographic studies revealed bihemispheric
      involvement during seizures, although magnetic resonance imaging (MRI) showed a
      marked right hemispheric atrophy. Hyperperfusion over the right hemisphere was
      seen with the performance of ictal single photon emission computed tomography
      (SPECT), which finally guided a right functional hemispherectomy and subsequent
      seizure control. CONCLUSION: Ictal SPECT could be a useful tool in the
      armamentarium of tools used for the localization of the epileptogenic focus in
      patients with Rasmussen's encephalitis and other localization-related epilepsies.

PMID- 16583734
TI  - Valvular heart disease in pergolide-treated Parkinson's disease.
AB  - BACKGROUND: A 61-year-old woman with Parkinson's disease, receiving pergolide
      1.75 mg four times daily, was admitted with progressive dyspnea. METHODS:
      Investigations revealed mitral and aortic regurgitation. She underwent surgical
      mitral replacement and aortic repair, but had a post-operative course
      characterized by repeated bouts of congestive heart failure. RESULTS: Severe
      tricuspid valve (TV) regurgitation developed within one month after the TV was
      reported on echocardiography to be relatively normal. Subsequent discontinuation
      of pergolide was associated with symptomatic improvement. CONCLUSIONS: This case
      illustrates the severity and rapidity with which cardiac valvular abnormalities
      can develop in patients receiving pergolide.

PMID- 16583735
TI  - Re: Methadone in the management of intractable neuropathic noncancer pain.

PMID- 16583736
TI  - In regards to the CCNS.

PMID- 16583737
TI  - [Analysis of the immunological pathogenesis of the seronegative autoimmune
      diseases].

PMID- 16583738
TI  - [Pneumocystis carinii pneumonia in patients with connective tissue diseases].

PMID- 16583739
TI  - [Rheumatoid factor and its related anti-IgG antibodies: the present state and
      perspective].

PMID- 16583740
TI  - [Intravenous immunoglobulin replacement therapy in X-linked agammaglobulinemia].
AB  - Intravenous immunoglobulin (IVIG) replacement therapy is the mainstay of therapy
      for X linked agammaglobulinemia (XLA). This study was attempted to investigate
      how patients with XLA were treated with IVIG in Japan. Data were complied from
      questionnaires filled in by the physicians. One hundred eighteen medical records
      had been given from 134 patients. One hundred eleven patients had been treated
      with IVIG. Most patients had been administered IVIG every 2 to 4 weeks, and
      maintained serum IgG trough levels of 400 mg/dl. Some of patients had adverse
      effects of IVIG. Antibiotics, especially macrolides, had been administered in
      some of patients. A few patients, despite the maintenance of higher trough
      levels, were associated with infections. The present study suggests that IVIG
      should be administered dependent on personal infection histories.

PMID- 16583741
TI  - [Case of hemophagocytic syndrome associated with active dermatomyositis].
AB  - We report a case of dermatomyositis (DM) with hemophagocytic syndrome (HPS). The
      patient is a 60 year old male admitted to our hospital with muscle weakness, high
      fever, weight loss and pancytopenia. On physical examination, proximal muscle
      weakness and skin rash on the back were noted. Laboratory data revealed elevated
      serum levels of muscle enzymes, lactate dehydrogenase and ferritin. Serum levels
      of M-CSF, TNF-alpha, soluble IL 2 receptor were remarkably increased. Bone marrow
      aspiration showed histiocytosis of 7 to 10% with prominent hemophagocytosis.
      Gastroendoscopic examination revealed II-a gastric cancer. He was treated with
      methylprednisolone (m-PSL) pulse theraphy (1 g/ day x 3 days) followed by 60
      mg/day oral prednisolone. He quickly responded to the treatment and laboratory
      data returned to normal in 20 days despite the remaining gastric cancer which was
      removed successfully 3 months later. HPS is a rare complication of DM and only
      three cases have been documented so far in the literature. Augmented cytokine in
      his serum is considered to be closely related to HPS in this case.

PMID- 16583742
TI  - Racial differences in health care use among medicare only and dual eligibles.
AB  - It has been an important financial issue in the U.S. Medicare expenditures that
      health care expenses of Medicaid-Medicare dual eligibles (MMDE) are much higher
      than those of Medicare only beneficiaries (MOB). This paper compares health care
      use and health status of MMDEs and MOBs who are either Afro-American or white
      recipients. Using total health care use information from the Medical Expenditure
      Panel Survey (MEPS) 2000, we find that the proportion of dual eligibles with
      chronic health conditions is higher by 4% than that of the Medicare only
      beneficiaries and that dual eligibles make more frequent uses of various health
      care services. The number of office-based physician visits and outpatient
      physician visits are higher for Afro-American dual eligibles than white dual
      eligibles. This finding seems to be contributed to by relatively high medical
      needs among dual eligibles. Higher utilization of agency-related home health
      services among Afro-American dual eligibles than among white dual eligibles is
      considered as a consequence of different ethnicity-specific responses to
      insurance coverage.

PMID- 16583743
TI  - Hospital choice by rural medicare beneficiaries: does hospital ownership matter?-
      a Colorado case.
AB  - About 45 percent of rural patients in Colorado bypassed their local rural
      hospitals during the 1990s. The effect of this phenomenon is a reduction in
      occupancy rates and a decrease in the competitiveness of rural hospitals, thereby
      ultimately causing rural hospitals to close and adversely affecting the
      communities that they were designed to serve. This study tests whether hospital
      ownership affects hospital choice by patients after controlling for institutional
      and individual dimensions. A conditional logistic regression is used to analyze
      Colorado Inpatient Discharge Data (CIDD) on 85,529 patients in addition to
      hospital data. Rural Medicare beneficiaries are influenced to choose a particular
      hospital by a combination of hospital characteristics (the number of beds, the
      number of services, accreditation, ownership type, and distance from patient
      residence) and patient characteristics (medical condition, age, gender, race, and
      total charge for services). Increasing rural hospitals' survivability,
      collaborating with other rural hospitals, expanding the number of available
      services, making strategic alliance with other providers are possible strategies
      that may help ward off encroachment by urban competitors.

PMID- 16583744
TI  - Enforcement of commercial violations by health professional regulatory boards: a
      research note.
AB  - This article explores the nature of disciplinary decisions of health professional
      regulatory boards in response to commercial violations by licensees. Decisions of
      the Virginia Boards of Dentistry, Medicine and Optometry are analyzed to assess
      the extent to which disciplinary decisions appear to protect the economic
      interests of professionals versus the health, safety and welfare of the public.
      Sanctions imposed on commercial and non-commercial violations are compared. Given
      the criticism that regulatory boards are more concerned with commercial practices
      rather than quality of care practices, it was expected that board disciplinary
      actions would reflect this concern. The results indicate that there is no
      significant difference in the severity of sanctions imposed on both types of
      violations. Commercial violations, when compared with non-commercial violations,
      are not sanctioned more harshly by regulatory boards. The implications for self
      interest theories of professional regulation and policies governing commercial
      practices of health professionals are discussed.

PMID- 16583745
TI  - Another evolvement of the cost and risk shifting model: consumer-driven health
      plans.
AB  - The US health care system has changed dramatically over the past forty years or
      so. This paper analyzes its potential transformation into a consumer-driven
      health care system (with the newly enacted HSAs and the increased popularity of
      employer defined contributions). The emphasis in the first part is the evolution
      of the role of providers (mostly physicians) into bearers of financial risk and
      gatekeepers. The second part discusses the new consumer-driven health care
      proposals and its potential impact on the future of health care as it pertains to
      putting consumers under financial risk and gives them a perceived sense of
      control over health care decisions.

PMID- 16583746
TI  - Co-morbidity in an elderly inpatient population: are the risks of co-existing
      conditions differentially distributed?
AB  - This study examines the distribution of co-morbidity among 167,738 inpatients,
      aged 65 or more, who experienced an episode of hospitalization during 1999 in
      short-term institutions that are located in Oklahoma. The analysis was conducted
      in two phases. In the first, logistic regression analysis was used to examine
      covariates that separate inpatients who presented at least one secondary
      diagnosis from those who were not co-morbid. Limited to those whose condition was
      complicated by at least one secondary diagnosis, Probit analysis was used to
      assess the covariates of the number of co-existing conditions. The covariates
      examined were the individual's racial status, demographic attributes, primary
      diagnosis, source of admission and discharge destination. Results indicate that
      the oldest of the elderly, African Americans and, to a lesser extent, Native
      Americans presented more complex cases than other members of the study
      population. The paper concludes with the policy implications that are associated
      with the differential distribution of co-morbidity.

PMID- 16583747
TI  - Home health care services: management and effectiveness in changing times.
AB  - New York City has the largest Medicaid personal care program (a form of home
      health care which includes many of the activities of daily living) in the country
      with approximately 45,000 clients and an annual budget of $1.5 billion. During
      the late 1980s and into the 1990s, New York State was experiencing budget
      difficulties, and established savings targets for local governments providing
      personal care services. In response, New York City, through its Home Attendant
      Program, began using different means of assessing clients' service needs to
      produce these savings. This article examines Task Based Assessment (a new service
      assessment methodology), and determines the degree to which it was successful,
      organizational issues that were faced by New York City and the 60 nonprofit and
      profit making companies contracted to deliver the service, legal challenges that
      were raised by advocacy groups and another alternative to the delivery of
      personal care services, a capitated long term care program. Task Based Assessment
      did not achieve its goals and the authors suggest, based on the positive
      experience from the capitated long term care program in controlling personal care
      hours, that it is more effective to expand these capitated programs than to seek
      to achieve further cost savings through the Home Attendant Program.

PMID- 16583749
TI  - Cash crisis hits public health plans.

PMID- 16583748
TI  - Acute QOF could reward trusts for good clinical performance.

PMID- 16583750
TI  - Sir Nigel walked, but where else sould the fingers point?

PMID- 16583751
TI  - On building "team NHS".

PMID- 16583752
TI  - Barometer. Mental health Feb 2006.

PMID- 16583754
TI  - Lean healthcare. Wait watchers.
AB  - Lean thinking helps speed up a patient's journey and cut waste by reworking
      routine procedures. Trusts are starting to use the theory in practice, with one
      doubling day surgery capacity and another redesigning its diagnostics procedures.
      Wasted time does not just frustrate patients - it can kill them.

PMID- 16583755
TI  - Long-term conditions. Tele addicts.
AB  - Dartford, Gravesham and Swanley PCT in Kent beat a government deadline to get
      community matrons in post. The telemedicine technology is being piloted in the
      country's largest trial of the equipment. The pitot covers patients with diabetes
      and heart and chest conditions.

PMID- 16583753
TI  - Cultural change. A turn for the better.
AB  - A dedicated turnaround team at St George's Healthcare trust has helped cuts its
      deficit in half in under two years. Work at Eastern Birmingham PCT could be under
      threat as a result of Commissioning a Patient-led NHS reforms. Cultural changes
      at South Yorkshire Ambulance

PMID- 16583756
TI  - Information. Mapping the money.
AB  - Dr Foster Intelligence aims to improve the use and accessibility of information
      to offer people more control over their care. It will also provide management
      with the information required to make effective business decisions. The new
      service will be 'taking advantage of private-sector expertise for public-sector
      advantage.

PMID- 16583758
TI  - On restructuring and redundancy.

PMID- 16583757
TI  - Prescriptions. Wave goodbye to paper.
AB  - Only 495,000 prescriptions have been processed electronically in the last year.
      This will rise to 1.3 million a day. Progress in pharmacies has been held up by
      out-of-date computer systems. The hope is that all practices and pharmacies will
      become partially enabled towards the end of this year, before transition to the
      full electronic service.

PMID- 16583759
TI  - On feedback.

PMID- 16583760
TI  - Bayes window.

PMID- 16583761
TI  - Disparity and shading cues cooperate for surface interpolation.
AB  - In two experiments, we tested whether disparity and shading cues cooperated for
      surface interpolation. Observers adjusted a probe dot to/lie on a surface
      specified either by a sparse disparity field, a continuous stereo shading or
      monocular shading gradient, or both cues. Observers' adjustments were very
      consistent with disparity information but their adjustments were much more
      variable with shading information. However, observers significantly improved
      their precision when both cues were present, relative to when only disparity
      information was present. These results cannot be explained by assuming that
      separate modules analyze disparity and shading information, even if observers
      optimally combined these cues. Rather, we attribute this improvement to a process
      through which the shading gradient constrains the disparity field in regions
      where disparities cannot be directly measured. This cooperative process may be
      based on the natural covariation existing between these cues produced by the
      retinal projection of smooth surfaces.

PMID- 16583762
TI  - Plaid motion rivalry: correlates with binocular rivalry and positive mood state.
AB  - Recently Hupe and Rubin (2003, Vision Research 43 531- 548) re-introduced the
      plaid as a form of perceptual rivalry by using two sets of drifting gratings
      behind a circular aperture to produce quasi-regular perceptual alternations
      between a coherent moving plaid of diamond-shaped intersections and the two sets
      of component 'sliding' gratings. We call this phenomenon plaid motion rivalry
      (PMR), and have compared its temporal dynamics with those of binocular rivalry in
      a sample of subjects covering a wide range of perceptual alternation rates. In
      support of the proposal that all rivalries may be mediated by a common switching
      mechanism, we found a high correlation between alternation rates induced by PMR
      and binocular rivalry. In keeping with a link discovered between the phase of
      rivalry and mood, we also found a link between PMR and an individual's mood state
      that is consistent with suggestions that each opposing phase of rivalry is
      associated with one or the other hemisphere, with the 'diamonds' phase of PMR
      linked with the 'positive' left hemisphere.

PMID- 16583763
TI  - An effect of luminance contrast on high-spatial-frequency tritanopia.
AB  - Luminance contrast was found to affect high-spatial-frequency tritanopia despite
      the S-cone coordinates of the stimuli being kept constant. This proves that a
      traditional account of artificial tritanopias based on the spatial resolution
      differences between the S-cone channel and the M- and L-cone channels is not
      applicable here. We suggest that the lack of spatial resolution in one of the
      post-receptor (rather than receptor) spatio-chromatic channels could be a cause
      of high-spatial-frequency tritanopia.

PMID- 16583764
TI  - Does perceptual belongingness affect lightness constancy?
AB  - The relation between perceptual belongingness and lightness perception has
      historically been studied in the contrast domain (Benary, 1924 Psychologische
      Forschung 5 131 - 142). However, scientists have shown that two equal grey
      patches may differ in lightness when belonging to different reflecting surfaces.
      We extend this investigation to the constancy domain. In a CRT simulation of a
      bipartite field of illumination, we manipulated the arrangement of twelve
      patches: six squares and six diamonds. Patches of the same shape could be placed:
      (i) all within the same illumination field; or (ii) forming a row across the
      illumination fields. Furthermore, we manipulated proximity between the innermost
      patches and the illumination edge. The patches could be (i) touching (forming an
      X-junction); or (ii) not touching (not forming an X-junction). Observers were
      asked to perform a lightness match between two additional patches, one
      illuminated and the other in shadow. We found better lightness constancy when the
      patches of the same shape formed a row across the fields, with no effect of X
      junctions. Since lightness constancy is improved by strengthening the
      belongingness across the illumination fields, we conclude that belongingness
      might help the visual system to aggregate the differently illuminated surfaces,
      and facilitate the scission process.

PMID- 16583765
TI  - Effects of endogenous spatial attention on the detection and discrimination of
      spatial frequencies.
AB  - Two experiments were designed to explore the relationship between visual
      attention and spatial-frequency processing using a cuing paradigm. In both
      experiments, the targets were a sharp-edged line segment with high spatial
      frequencies present and a blurred line segment with only low spatial frequencies
      present. In each trial an endogenous cue appeared at fixation indicating the
      probable location, left or right, in which a stimulus would appear. In experiment
      1, a typical cuing effect was found with simple reaction times (RTs) for
      detecting the stimuli being faster when they appeared at a cued (ie attended)
      compared to an uncued (ie unattended) location. In experiment 2, choice RTs were
      measured, with participants indicating whether the sharp-edged line segment or
      the blurred line segment was presented in each trial. In this case, when it was
      necessary to process the spatial-frequency content of the stimuli, RTs were
      significantly faster at the attended location only for the sharp-edged line
      segment. For the blurred line segment without high spatial frequencies, RTs did
      not differ for attended and unattended locations. The results indicate that
      endogenous spatial attention interacts differently with high-spatial-frequency
      and low-spatial-frequency selective mechanisms depending on whether the task is
      to detect a stimulus or identify it on the basis of its spatial-frequency
      content.

PMID- 16583766
TI  - Testing the tilt-constancy theory of visual illusions.
AB  - Prinzmetal and Beck (2001) Journal of Experimental Psychology: Human Perception
      and Performance 27 206 - 217) argued that a subset of visual illusions is caused
      by the same mechanisms that are responsible for the perception of vertical and
      horizontal a theory they referred to as the tilt-constancy theory of visual
      illusions. They argued that these illusions should increase if the observer's
      head or head and body are tilted because extra reliance would then be placed on
      the illusion-inducing local visual context. Exactly that result had previously
      been reported in the case of the tilted-room and the rod-and-frame illusions.
      Prinzmetal and Beck reported similar increases in the tilt illusion (TI), as well
      as the Zollner, Poggendorff, and Ponzo illusions. In two experiments, we re
      examined the effect of head tilt on the TI. In experiment 1, we used more
      conventional TI stimuli, more standard experimental methods, and a more complete
      experimental design than Prinzmetal and Beck, and additionally extended the
      investigation to attraction as well as repulsion effects. Experiment 2 more
      closely replicated the Prinzmetal and Beck stimuli. Although we found that head
      tilt did increase TIs in both experiments, the increases were of the order of 1
      degrees -2 degrees, more modest than the 7 degrees reported by Prinzmetal and
      Beck. Significantly, the TI increase was larger when inducing tilts and head
      tilts were in the same direction than when they were in opposite directions,
      suggesting that the tilt-constancy theory may be oversimplified. In addition,
      because previous evidence renders unlikely the claim that the Poggendorff
      illusion can be explained simply in terms of misperceived orientation of the
      transversals, the question arises whether there might be some other explanation
      for the increase in the Zollner, Poggendorff, and Ponzo illusions with body tilt
      that Prinzmetal and Beck reported.

PMID- 16583767
TI  - The perception of moving subjective contours by 4-month-old infants.
AB  - We investigated whether 4-month-old infants are capable of perceiving illusory
      contours produced by the Kanizsa-square display, first introduced by Prazdny
      (1983, Perception & Psychophysics 34 403-404), which tests whether a viewer
      perceives the illusory contour in the absence of brightness contrast (illusory
      brightness). Because the illusory square appears to move across the computer
      screen and infants are attracted to motion, this display holds their interest. In
      experiment 1, 4-month-old infants were tested for their ability to distinguish
      between a continuously moving illusory square and a continuously moving control
      display in which the pacman elements were rotated so that the perception of
      subjective contours did not occur. Data analysis revealed a significant
      preference for the subjective contour display. In experiment 2, habituation
      dishabituation was used with 4-month-old infants. They were tested for their
      ability to discriminate between the illusory Kanizsa square that continuously
      moved back and forth and an illusory square which changed positions randomly.
      Although the infants did not show differences in dishabituation as a function of
      the habituation display, they looked significantly longer at the continuously
      moving display.

PMID- 16583768
TI  - Aesthetic phenomena as supernormal stimuli: the case of eye, lip, and lower-face
      size and roundness in artistic portraits.
AB  - In the first study, eye and lip size and roundness, and lower-face roundness were
      compared between a control sample of 289 photographic portraits and an
      experimental sample of 776 artistic portraits covering the whole period of the
      history of art. Results showed that eye roundness, lip roundness, eye height, eye
      width, and lip height were significantly enhanced in artistic portraits compared
      to photographic ones. Lip width and lower-face roundness, on the contrary, were
      less prominent in artistic than in photographic portraits. In a second study,
      forty-two art academy students were requested to draw two self-portraits, one
      with a mirror and one without (from memory). Eye, lip, and lower-face roundness
      in artistic self-portraits was compared to the same features derived from
      photographic portraits of the participants. The results obtained confirmed those
      found in the first study. Eye and lip size and roundness were greater in artistic
      self-portraits, while lower-face roundness was significantly reduced. The same
      degree of modification was found also when a mirror was available to the
      subjects. In a third study the effect of lower-face roundness on the perception
      of attractiveness was assessed: fifty-three participants had to adjust the face
      width of 24 photographic portraits in order to achieve the highest level of
      attractiveness. Participants contracted the face width by a mean value of 5.26%,
      showing a preference for a reduced lower-face roundness. All results are
      discussed in terms of the importance of the 'supernormalisation' process as a
      means of assigning aesthetic value to perceptual stimuli.

PMID- 16583769
TI  - Numerosity judgments for tactile stimuli distributed over the body surface.
AB  - A large body of research now supports the claim that two different and
      dissociable processes are involved in making numerosity judgments regarding
      visual stimuli: subitising (fast and nearly errorless) for up to 4 stimuli, and
      counting (slow and error-prone) when more than 4 stimuli are presented. We
      studied tactile numerosity judgments for combinations of 1-7 vibrotactile stimuli
      presented simultaneously over the body surface. In experiment 1, the stimuli were
      presented once, while in experiment 2 conditions of single presentation and
      repeated presentation of the stimulus were compared. Neither experiment provided
      any evidence for a discontinuity in the slope of either the RT or error data
      suggesting that subitisation does not occur for tactile stimuli. By
      systematically varying the intensity of the vibrotactile stimuli in experiment 3,
      we were able to demonstrate that participants were not simply using the 'global
      intensity' of the whole tactile display to make their tactile numerosity
      judgments, but were, instead, using information concerning the number of tactors
      activated. The results of the three experiments reported here are discussed in
      relation to current theories of counting and subitising, and potential
      implications for the design of tactile user interfaces are highlighted.

PMID- 16583770
TI  - The perception of tempo in music.
AB  - Tempo is one factor that is frequently associated with the expressive nature of a
      piece of music. Composers often indicate the tempo of a piece of music through
      the use of numerical markings (beats min(-1)) and subjective terms (adagio,
      allegro). Three studies were conducted to assess whether listeners were able to
      make consistent judgments about tempo that varied from piece to piece. Listeners
      heard short extracts of Scottish music played at a range of tempi and were asked
      to make a two-alternative forced choice of "too fast" or "too slow" for each
      extract. The responses for each study were plotted as proportion of too fast
      responses as a function of tempo for each piece, and cumulative normal curves
      were fitted to each data set. The point where these curves cross 0.5 is the tempo
      at which the music sounds right to the listeners, referred to as the optimal
      tempo. The results from each study show that listeners are capable of making
      consistent tempo judgments and that the optimal tempo varies across extracts. The
      results also revealed that rhythm plays a role, but not the only role in making
      temporal judgments.

PMID- 16583771
TI  - Can you do this? Extremely difficult interbodypart coordination tasks and
      implications for central limitations on control of coordination.
AB  - We have recently noticed our own inability to perform a number of interbodypart
      coordination tasks. The inability to perform these tasks indicates an intriguing
      central processing limitation on movement control, and study of these tasks
      should be helpful in understanding the neural mechanisms of motor control.

PMID- 16583772
TI  - You make me sick: marital quality and health over the life course.
AB  - We work from a life course perspective and identify several reasons to expect age
      and gender differences in the link between marital quality and health. We present
      growth curve evidence from a national longitudinal survey to show that marital
      strain accelerates the typical decline in self-rated health that occurs over time
      and that this adverse effect is greater at older ages. These findings fit with
      recent theoretical work on cumulative adversity in that marital strain seems to
      have a cumulative effect on health over time-an effect that produces increasing
      vulnerability to marital strain with age. Contrary to expectations, marital
      quality seems to affect the health of men and women in similar ways across the
      life course.

PMID- 16583773
TI  - Financial strain over the life course and health among older adults.
AB  - This paper focuses on financial strain across the life course as a condition
      underlying health inequalities observed in later life. The analysis is based on
      data from 1167 adults 65 years and older collected as part of the 'Aging, Stress
      and Health Study". Relying on retrospective data about hardship experienced over
      the life course, we find that long-term financial hardship is reflected in a
      range of health outcomes at late life, even after controlling for the effects of
      current financial circumstances. Moreover, the sheer persistence of hardship
      matters more than its episodic occurrence or timing, so that the health effects
      of early hardship may be obviated if followed by no further hardship. This
      pattern offindings is consistent with the notion of allostatic load, the
      cumulative damage done to health and well-being under the burden of an
      unrelenting stressor in a critically important life domain.

PMID- 16583774
TI  - Nonresident fathers' involvement and adolescents' smoking.
AB  - Although prior research has shown that adolescents from divorced and separated
      households are more likely to smoke than their peers from intact families, few
      studies have addressed factors that may minimize this risk, such as the role of
      involvement by nonresident fathers. A sample from the National Longitudinal Study
      of Adolescent Health (Add Health) is used to examine the longitudinal effects of
      nonresident fathers 'involvement, changes in involvement, and fathers' modeling
      of smoking behavior on the probability that adolescents will begin smoking
      regularly. Results indicate that adolescents who are more involved with their
      fathers are less likely to begin smoking regularly, that changes in involvement
      over time predict changes in the probability that adolescents will begin to smoke
      regularly, and that fathers' smoking also affects this outcome. Implications for
      theory and public policy are discussed.

PMID- 16583775
TI  - The gender structure of adolescent peer influence on drinking.
AB  - The interactions of adolescent peers are the subject of both parental angst and
      scholarly attention. Peer influence is the most consistent predictor of
      adolescent drinking patterns when controlling for other background
      characteristics. This study extends these findings to incorporate a theoretical
      argument derived from status characteristics theory. Using 2980 best-friend dyads
      constructed from the National Longitudinal Study ofAdolescent Health ("Add
      Health"), I show that the peer influence process differs by the gender structure
      of the friendship. Adolescents in same-sex best friendships influence one another
      mutually, consistent with prior theoretical and empirical approaches to
      adolescent problem behavior: By contrast, boys in mixed-sex best friendships have
      influence over their female friends' drinking patterns, while the girls do not
      have any effect on their male friends' drinking behavior a finding consistent
      with status characteristics theory. The results indicate that peer influence
      models that do not take gender into account in the structure of the friendship
      misrepresent the unequal influence dynamics between boys and girls.

PMID- 16583776
TI  - Multiple roles and mental health in cross-cultural perspective: the elderly in
      the United States and Japan.
AB  - This paper examines how multiple roles affect the mental health of the elderly in
      Japan and the United States, two countries with vastly different cultures.
      Hypotheses were drawn based on the cultural differences in role experiences, and
      these hypotheses are tested by analyzing nationally representative samples of the
      elderly in these countries. The results show that Americans are more likely to be
      involved in roles related to family, work, and community, while the Japanese are
      more likely to be involved in only those roles related to family and work.
      Multiple roles are also found to be less beneficialfor the mental health of
      Japanese elderly compared to American counterparts. National differences in the
      effects of individual roles and role configurations on mental health are also
      documented. Overall, the results show the importance of broad cultural contexts
      for understanding the relationship between roles and mental health.

PMID- 16583777
TI  - Health and the education of children from racial/ethnic minority and immigrant
      families.
AB  - Building on a conceptual model of the transition to elementary school, this study
      explored the role of health in the early cognitive achievement of children from
      various racial/ethnic minority and immigrant families by applying multilevel
      modeling to data from a nationally representative sample of American
      kindergarteners. Whites tended to have the best physical health before
      transitioning to first grade. Children from immigrant Latino/a and Asian families
      had the worst physical health but the best mental health. Compared to white
      children from native families, these health differentials partially explained the
      lower math achievement and achievement growth of black children (whether from
      native or immigrant families) in first grade as well as the lower math
      achievement of children from Latino/a immigrant families and the lower
      achievement growth of children from Asian immigrant families during this period.

PMID- 16583778
TI  - Porcine circovirus diseases.
AB  - Porcine circovirus type 2 (PCV2) is a member of the family Circoviridae, a
      recently established virus family composed of small, non-enveloped viruses, with
      a circular, single-stranded DNA genome. PCV2, which is found all over the world
      in the domestic pig and probably the wild boar, has been recently associated with
      a number of disease syndromes, which have been collectively named porcine
      circovirus diseases (PCVD). Postweaning multisystemic wasting syndrome (PMWS),
      porcine dermatitis and nephropathy syndrome (PDNS) and reproductive disorders are
      the most relevant ones. Among them, only PMWS is considered to have a severe
      impact on domestic swine production. PMWS mainly affects nursery and/or fattening
      pigs; wasting is considered the most representative clinical sign in this
      disease. Diagnosis of this disease is confirmed by histopathological examination
      of lymphoid tissues and detection of a moderate to high amount of PCV2 in damaged
      tissues. Since PMWS is considered a multifactorial disease in which other factors
      in addition to PCV2 are needed in most cases to trigger the clinical disease,
      effective control measures have focused on the understanding of the co-factors
      involved in individual farms and the control or elimination of these triggers.
      PDNS, an immuno-complex disease characterized by fibrino-necrotizing
      glomerulonephritis and systemic necrotizing vasculitis, has been linked to PCV2,
      but a definitive proof of this association is still lacking. PCV2-associated
      reproductive disease seems to occur very sporadically under field conditions, but
      it has been characterized by late-term abortions and stillbirths, extensive
      fibrosing and/or necrotizing myocarditis in fetuses and the presence of moderate
      to high amounts of PCV2 in these lesions. Taking into account that scientific
      information on PCV2 and its associated diseases has been markedly expanded in the
      last 8 years, the objective of this review is to summarize the current state of
      knowledge of the most relevant aspects of PCV2 biology and PCVD.

PMID- 16583779
TI  - Passive and active components of neonatal innate immune defenses.
AB  - Innate immune defenses are crucial for survival in the first days and weeks of
      life. At birth, newborns are confronted with a vast array of potentially
      pathogenic microorganisms that were not encountered in utero. At this age,
      cellular components of the adaptive immune system are in a naive state and are
      slow to respond. Antibodies received from the dam are essential for defense, but
      represent a finite and dwindling resource. Innate components of the immune system
      detect pathogen-associated molecular patterns (PAMPs) on microorganisms (and
      their products) by means of pattern-recognition receptors (PRRs). Soluble
      mediators of the innate system such as complement proteins, pentraxins,
      collectins, ficolins, defensins, lactoferrin, lysozyme etc. can bind to
      structures on pathogens, leading to agglutination, interference with receptor
      binding, opsonization, neutralization, direct membrane damage and recruitment of
      additional soluble and cellular elements through inflammation. Cell-associated
      receptors such as the Toll-like receptors (TLRs) can activate cells and
      coordinate responses (both innate and adaptive). In this paper, accumulated
      knowledge of the receptors, soluble and cellular elements that contribute to
      innate defenses of young animals is reviewed. Research interest in this area has
      been intermittent, and the literature varies in quantity and quality. It is hoped
      that documentation of the limitations of our knowledge base will lead to more
      extensive and enlightening studies.

PMID- 16583780
TI  - Gastrointestinal nematode infection in sheep--a review of the alternatives to
      anthelmintics in parasite control.
AB  - Efforts to curb production losses caused by nematode parasitism in sheep have led
      to the development of a number of control methods to complement or replace
      anthelmintics. The need for alternative control measures stems from the emergence
      of anthelmintic-resistant parasitic nematodes with reports of multi-class
      resistance to these drugs now emerging. A number of these control methods such as
      predacious microfungi, protein supplementation, plant extracts in feed and
      vaccines have demonstrated potential to control infection but require development
      and examination under natural conditions. Breeding for natural resistance to
      nematode infection has already shown success in controlling the disease under
      natural conditions. Selection for resistance is currently based on fecal egg
      count measurements but identification of genetic indicators of resistance will
      provide a more efficient method of selection. Current quantitative trait loci for
      nematode resistance include the MHC genes, interferon gamma gene, IgE gene and
      microsatellites on chromosome 1, 5 and 6. This paper reviews the current
      alternatives to anthelmintics to control infection, with an emphasis on breeding
      for host resistance and identification of genetic indicators of resistance.

PMID- 16583781
TI  - Proliferative enteropathy: a global enteric disease of pigs caused by Lawsonia
      intracellularis.
AB  - Proliferative enteropathy (PE; ileitis) is a common intestinal disease affecting
      susceptible pigs raised under various management systems around the world. Major
      developments in the understanding of PE and its causative agent, Lawsonia
      intracellularis, have occurred that have led to advances in the detection of this
      disease and methods to control and prevent it. Diagnostic tools that have
      improved overall detection and early onset of PE in pigs include various
      serological and molecular-based assays. Histological tests such as
      immunohistochemistry continue to be the gold standard in confirming Lawsonia
      specific lesions in pigs post mortem. Despite extreme difficulties in isolating
      L. intracellularis, innovations in the cultivation and the development of pure
      culture challenge models, have opened doors to better characterization of the
      pathogenesis of PE through in vivo and in vitro L. intracellularis-host
      interactions. Advancements in molecular research such as the genetic sequencing
      of the entire Lawsonia genome have provided ways to identify various immunogens,
      metabolic pathways and methods for understanding the epidemiology of this
      organism. The determinations of immunological responsiveness in pigs to virulent
      and attenuated isolates of L. intracellularis and identification of various
      immunogens have led to progress in vaccine development.

PMID- 16583782
TI  - Plant-made vaccines: biotechnology and immunology in animal health.
AB  - The use of plants as production systems for vaccine antigens has been actively
      investigated over the last 15 years. The original research focused on the value
      of this expression system for oral delivery based on the hypothesis that plant
      expressed antigens would be more stable within the digestive tract and would
      allow for the use of the oral route of administration to stimulate a mucosal
      immune response. However, while first conceived for utility via the oral route,
      plant-made antigens have also been studied as classical immunogens delivered via
      a needle to model animal systems. Antigens have been expressed in a number of
      whole plant and cell culture systems. Several alternative expression platforms
      have been developed to increase expression of antigens or to elicit preferred
      immunological responses. The biotechnological advances in plant expression and
      the immunological testing of these antigens will be reviewed in this paper
      focusing primarily on diseases of livestock and companion animals.

PMID- 16583783
TI  - Listeria monocytogenes: silage, sandwiches and science.
AB  - Listeria monocytogenes is amongst the most intriguing and well studied of the
      pathogenic bacteria. However, the understanding and perspective one has of L.
      monocytogenes depends to a large extent on the microbiological issues with which
      one is faced as a part of your professional duties. The focus of the veterinary
      clinician or investigator is likely to be foremost on the neurologic (circling
      disease) and reproductive diseases L. monocytogenes causes. To the food
      microbiologist, the principal concern is to prevent introduction of L.
      monocytogenes into food products, or to identify its presence and prevent its
      multiplication to numbers of organisms that are likely to pose a substantial risk
      to humans who ingest the product. To the cellular immunologist, listeriosis
      represents a robust murine model that helped to elucidate many important concepts
      in innate and adaptive immunity, and L. monocytogenes is a potential vector for
      delivery of novel vaccines. To the student of molecular pathogenesis, L.
      monocytogenes is a powerful and well-characterized model organism for studying
      the cellular microbiology of an intracellular pathogen. In this brief overview, I
      will attempt to highlight some of the classical observations, and contemporary
      insights, on L. monocytogenes and listeriosis, and integrate these perspectives
      into a common framework. By so doing, I hope to provide those with one
      perspective on listeriosis with an appreciation of the broad array of problems
      and issues faced by those who focus on some other aspect of L. monocytogenes and
      its pathogenesis.

PMID- 16583784
TI  - Demystifying the list: necessary ingredients for a credible drug formulary.

PMID- 16583785
TI  - The effect of price changes on utilization.

PMID- 16583786
TI  - Effects of the ritonavir price increase on the cost of protease inhibitor
      regimens in United States.
AB  - In late 2003, one manufacturer effected a fivefold increase in the price of its
      protease inhibitor (PI) ritonavir. Using the average wholesale price of each
      treatment regimen, IMS Health marketshare data, and epidemiologic data, the
      authors analyzed the effect of this price increase on the direct cost of
      ritonavir-boosted PI regimens. If 75% of individuals living with acquired
      immunodeficiency syndrome and 50% of those with human immunodeficiency virus
      infection in 2003 were receiving PI regimens, the total direct cost after the
      price rise was dollar 4 billion, an increase approaching dollar 1 billion.
      Moreover, the estimates of increased costs obtained in this study are assumed to
      be conservative.

PMID- 16583787
TI  - Headache medicine usage patterns.

PMID- 16583788
TI  - Clinical classifications software for identification of codes.

PMID- 16583789
TI  - The effect of depression on health care utilization and costs in patients with
      type 2 diabetes.
AB  - The objective of the study was to estimate the effect of depression on health
      care utilization and costs in patients newly diagnosed with type 2 diabetes.
      Patients were identified during a four-year enrollment period (1998-2001) from a
      Medicaid claims database. The final cohort consisted of 4,294 patients with type
      2 diabetes (1,525 patients with depression; 2,769 patients without depression).
      Multivariate results indicated that significant utilization differences existed
      between the two groups: Patients who were depressed incurred a higher number of
      physician office visits, emergency room/inpatient admissions, and more
      prescriptions compared with patients who had diabetes but were not depressed.
      Patients with depression had nearly 65% higher overall health care costs than
      those without depression. Recognizing that depression is as a risk factor for
      increasing health care expenditures has the potential to improve diabetes
      management and related outcomes.

PMID- 16583790
TI  - Proposed rules for electronic medical records and e-prescribing: do they go far
      enough.
AB  - Recent proposals by the U.S. Department of Health and Human Services for more
      antikickback safe harbors and exceptions to the Stark law are intended to ease
      the restrictions on electronic medical records and E-prescribing arrangements,
      and support government efforts to promote widespread adoption of the technology.
      Do these proposals go far enough? This article examines the agency's proposals
      and their practical effects.

PMID- 16583791
TI  - English language learners, LD, and overrepresentation: A multiple-level analysis.
AB  - Continuing unresolved problems in the field of special education include the
      continued use of discrepancy models; the need for better identification models;
      continued debate over programmatic issues, ranging from inclusion to self
      contained models; and the continued overrepresentation of certain ethnic and
      racial groups in the learning disabilities (LD) category. This article focuses on
      students with mild learning disorders in general, and LD in particular, providing
      a perspective on how this problem has been addressed and suggesting a multilevel
      approach in which local context plays a central role. We suggest that
      overrepresentation is best conceptualized as an indicator of underlying issues
      rather than as the proper focal point of remediation efforts.

PMID- 16583792
TI  - English language learners who struggle with reading: language acquisition or LD?
AB  - We review empirical research on English language learners (ELLs) who struggle
      with reading and who may have learning disabilities (LD). We sought to determine
      research indicators that can help us better differentiate between ELLs who
      struggle to acquire literacy because of their limited proficiency in English and
      ELLs who have actual LD. We conclude that more research is warranted to further
      elucidate the strengths and learning needs of subgroups of underachieving ELLs,
      to help us determine who should qualify for special education, and to clarify why
      some ELLs who do not have LD still struggle with language and literacy
      acquisition. Future research should account for the complexities involved in
      becoming literate in another language and focus more on cultural and contextual
      factors that affect student achievement.

PMID- 16583793
TI  - English language learners with reading-related LD: linking data from multiple
      sources to make eligibility determinations.
AB  - Results are reported for an exploratory study of eligibility decisions made for
      21 Spanish-speaking English language learners (ELLs) with learning disabilities
      (LD) and no secondary disabilities who received special education support in
      reading. Eligibility determinations by an expert panel resulted in decisions that
      differed significantly from those of school multidisciplinary teams. The panel
      agreed that some students appeared to have reading-related LD (n = 5) but also
      identified students that they believed had disabilities, but not necessarily
      reading-related LD (n = 6). Another group of students (n = 10) had learning
      problems that the panel believed could be attributed to factors other than LD or
      for whom substantive additional data would be required to validate eligibility.
      Issues associated with referral, assessment, and eligibility determinations for
      ELLs are discussed, and recommendations for improving practice are offered, with
      an emphasis on the importance of linking data from multiple sources when deciding
      whether ELLs qualify for special education.

PMID- 16583794
TI  - Roles of definitional and assessment models in the identification of new or
      second language learners of English for special education.
AB  - This article examines the efficacy of current definitional perspectives on
      learning disabilities (LD) and related assessment models to support appropriate
      instructional and support services for learners of English with learning-related
      difficulties. A revised framework for defining LD and an associated assessment
      model, curriculum-based dynamic assessment (CDA), are proposed. The results of a
      teacher assessment study are reported to exemplify how this revised framework may
      be studied. The study examined the following questions: (a) Can curriculum-based
      dynamic assessments of authentic learning tasks help educators to differentiate
      between the work of students with limited English proficiency and their peers
      identified as having LD? (b) What are the characteristics of curriculum-based
      work samples of limited English proficient students with LD that may predictably
      differentiate them from their peers without LD?

PMID- 16583795
TI  - Response to intervention as a vehicle for distinguishing between children with
      and without reading disabilities: Evidence for the role of kindergarten and first
      grade interventions.
AB  - Children at risk for early reading difficulties were identified on entry into
      kindergarten, and half of these children received small-group intervention two to
      three times a week during their kindergarten year. The other half received
      whatever remedial assistance was offered by their home schools. These children
      were again assessed at the beginning of first grade, and those who continued to
      have difficulties in reading received either one-to-one daily tutoring offered by
      project teachers from the beginning to the end of first grade or whatever
      remedial assistance was offered by their home schools over the same time period.
      All target children were periodically assessed through the end of third grade.
      Results suggest that either kindergarten intervention alone or kindergarten
      intervention combined with first-grade intervention are both useful vehicles for
      preventing early and long-term reading difficulties in most at-risk children.

PMID- 16583796
TI  - How should "unresponsiveness" to secondary intervention be operationalized? It is
      all about the nudge.
AB  - In the fourth session of the National Research Center on Learning Disabilities
      Responsiveness-to-Intervention Symposium in 2003, Good, Vellutino, and Torgesen
      presented papers that addressed the question, "How should unresponsiveness to
      secondary intervention be operationalized in an RTI approach to LD
      identification?" In this commentary, I highlight important areas in which ideas
      converge across the three presentations. I argue that it will be important, as
      the field begins to grapple with a definition of "unresponsiveness" to secondary
      intervention, that we also specify who should get the intervention, what the
      intervention should consist of, when the intervention should occur, how long the
      intervention should last, and by whom the intervention should be applied. Only
      then can we accurately assess the merits of competing definitions of
      unresponsiveness.

PMID- 16583797
TI  - Arithmetic processing in children with spina bifida: Calculation accuracy,
      strategy use, and fact retrieval fluency.
AB  - Three studies compared 98 children with spina bifida myelomeningocele (SBM)-a
      disorder associated with high rates of math disability and spatial deficits-to 94
      typically developing children on multidigit subtraction and cognitive addition
      tasks. Children with SBM were classified into those with reading decoding and
      math disability, only math disability, and no reading or math disability. Study 1
      showed that visual-spatial errors in multidigit arithmetic were not elevated in
      children with SBM. In Study 2, deficits in accuracy, speed, and strategy-use in
      single-digit addition characterized groups with math disability regardless of
      reading status. Accuracy and speed on single-digit addition was strongly related
      to performance on multidigit subtraction. A math-level matching design in Study 3
      revealed less mastery of math facts by the group with SBM. The results are
      discussed with reference to cognitive and neuropsychological models of math
      disability.

PMID- 16583799
TI  - [Use of drug-coated stents to treat coronary bifurcation lesions].
AB  - Bifurcation stenoses are one of the most complex categories for endovascular
      treatment as such lesion requires that the lumen of both a great vessel and a
      lateral branch be recovered. Introduction of drug-coated stents into clinical
      practice has changed surgical approaches in this type of an atherosclerotic
      lesion. The use of two drug-coated endoprostheses or more within the afflicted
      segment to stent a great vessel or lateral branch does not increase a risk for
      restenosis. The considerable opportunities of endovascular technologies and the
      absence of a unified surgical approach in this type of lesion generate a need for
      systematizing the experience accumulated. The purpose of the present study is to
      develop an algorithm of bifurcation stenting in different types of X-ray anatomy
      and morphology of a coronary lesion.

PMID- 16583798
TI  - [To differential diagnosis of esophageal cancer and other diseases with the
      similar clinical symptoms, by using traditional X-ray study].
AB  - The principal purpose of the paper is to assess the role of the X-ray section of
      current radiation diagnosis in obtaining objective information and interpreting
      it in esophageal cancer. The study was methodically based on its serial studies,
      by comparing the data of clinical, radiation, and endoscopic diagnosis with those
      of morphological studies of the biopsy specimens taken at resection for cancer of
      the esophagus and the upper stomach, and histologically examined them in diseases
      running with the similar clinical symptoms. The complex of radiation techniques
      included traditional X-ray study (compact filling, double contrasting). A
      specially developed procedure that allowed physicians the opportunity to examine
      the cardioesophageal area in the fragmentary fashion was used during
      morphological studies. In cancer of the upper stomach, the lower esophageal
      segments were also involved in the process in 79.9%. It should be also noted that
      this number of observations includes some cases that clinical symptomatology and
      endoscopy strongly suggest cancer of the lower third of the esophagus. The
      authors have arrived at the conclusion that the present-day X-ray semiotics of
      esophageal diseases running with the similar clinical symptomatology permits
      their differential diagnosis just before the use of endoscopy and histology of
      biopsy specimens and that the unique advantage of radiation diagnosis over
      endoscopy is to specify the initial site of a tumor, namely, to detect primary
      gastric damage in cardioesophageal carcinoma.

PMID- 16583800
TI  - [The CR digital radiography system in traditional X-ray studies (according to the
      materials of the Moscow Regional Clinical Research Institute)].
AB  - The basic idea of the author's paper is to attempt to estimate and prove whether
      it is advisable to use the CR digital radiography system in a multidisciplinary
      therapeutic institution mainly at the municipal level. The pre-requisites for
      this were the results of diagnostic studies of different diseases of organs and
      systems. Emphasis is laid on the specific features of use of this digital system;
      namely, it can convert several analogue X-ray apparatuses to digital ones and it
      is more profitable than indirect image numeralization apparatuses and produces
      lower radiation loads. This all makes the use of these digital systems tempting
      in traditional X-ray study. A comparatively large material (4237 cases) was used
      to show the efficiency of the CR digital radiography system in the diagnosis of
      ENT diseases, osteology, interventional radiology, gastroenterology, pediatrics
      and to demonstrate a modernized approach to having a solid copy of a digital
      image, the possibilities of postprocessing that may enhance the validity of
      existing X-ray symptoms. This all allows the author to recommend that the CR
      digital radiography systems be used in traditional X-ray study for the diagnosis
      of various diseases occurring in a multidisciplinary health care facility mainly
      at municipal and regional levels.

PMID- 16583801
TI  - [Screening for breast cancer in females at the level of regional (territorial,
      republican) clinical hospitals: organizational and methodological aspects].
AB  - The paper deals with a special screening for breast cancer in female visitors of
      the consultative-and-diagnostic units (CDU) of regional (territorial, republican)
      clinical hospitals in the Russian Federation. The study was conducted in the CDU
      of the Moscow Regional Clinical Research Institute that in addition to its
      clinical researches acts as a regional clinical hospital for the Moscow Region.
      The basic idea of this screening is firstly that specialists of such-level CDU
      attended by many women requiring various consultations obligatorily give
      multifaceted counseling. Secondly, such polyclinic complexes have a required set
      of technical devices, such as as radiomammographs, ultrasound apparatuses, etc.
      In other words, there are prerequisites for providing a present-day screening,
      without spending any extra money. This screening has been made at the Institute
      since 2002. A total of 2724 risk-group females and 4222 female patients with the
      clinical signs of breast space-occupying lesions were examined. Its procedure
      including the formation of risk groups has been developed by means of a specially
      designed questionnaire. A comparative analysis of the results of these
      examinations gives preference to the screening diagnosis of this pathology. This
      all makes the author recommend this screening for its use in all 89 regions of
      the Russian Federation, by understanding that this can partially solve the
      problem of a screening for breast cancer in women in general outpatient care
      health facilities at the municipal level. Moreover, any attempts to mage a
      screening diagnosis of tumorous lesions at this level of today's health care
      become particularly relevant in the light of the governmental program to be
      implemented, which focuses on municipal public health that is one of its main
      goals.

PMID- 16583802
TI  - [Solid tumors of internal female reproductive organs: comparison of the
      diagnostic efficiency of ultrasound study and magnetic resonance tomography].
AB  - Comparison of the diagnostic importance of traditional US and low-field MRI (0,23
      T) in the characterization of solid tumors of internal reproductive system at 55
      patients is performed by calculation of operational characteristics of tests and
      use of characteristic curves (ROC-analysis). Advantage MRI in distinguishing
      between of benign and malignant tumors (accuracy of 82% against 71% at
      ultrasonic) is established. Advantage is based on use, besides morphological
      criteria of a tumor, the characteristic of its MR-signal in T2-weight imaging.
      Advantage MRI in determination of the organ of origin of pelvic mass appeared
      insignificant.

PMID- 16583803
TI  - [Mediastinal lymphogranulomatosis (a clinical note)].

PMID- 16583804
TI  - [Potentialities of ultrasound diagnosis of the articular syndrome in
      rheumatology].

PMID- 16583805
TI  - [Cases of Crohn's disease involving the small bowel, diagnosed by the barium
      contrast agent ENTERO-VU].
AB  - The paper deals with the capacities of X-ray diagnosis of Cronh's disease
      involving the small bowel, using the barium contract agent Entero-VU specially
      designed to examine the bowel. It describes 3 cases of Crohn's disease presented
      by its different stages and localization in the small bowel. In the author's
      opinion, the barium contrast agent Entero-VU designed to examine the small bowel
      has two basic advantages: it is easy-to-use and highly diagnostically effective.

PMID- 16583806
TI  - Underserved rural Georgia.

PMID- 16583807
TI  - No matter where you live.

PMID- 16583808
TI  - Pay attention to demographics.

PMID- 16583809
TI  - Rural needs.

PMID- 16583810
TI  - Tri-County Health System, Inc. Enduring example of effective rural health care.

PMID- 16583811
TI  - Facing rural Georgia's health care issues.

PMID- 16583812
TI  - General surgery, ambulatory surgery centers--a battle ahead.

PMID- 16583813
TI  - Is there a doctor in the house? A look at Georgia's current and future physician
      workforce needs.

PMID- 16583814
TI  - Living and working in a small town in Georgia.

PMID- 16583815
TI  - MAG member studies obesity risk factor for aggressive prostate cancer.

PMID- 16583816
TI  - MAG member investigates breast cancer detector that uses electricity instead of x
      rays.

PMID- 16583817
TI  - Ritter investigates breast cancer using growth factors to lure stem cells.

PMID- 16583818
TI  - MCG, Georgia Cancer Coalition tumor bank supports cancer research.

PMID- 16583820
TI  - Enhanced degradation efficiency of toluene using titania/silica photocatalysis as
      a regeneration process.
AB  - Three kinds of titania/silica pellets were prepared using the sol-gel method with
      surface areas of 50.4 m2 g(-1), 421.1 m2 x g(-1) and 89.1 m2 x g(-1). An annular
      reactor was designed and built to determine the degradation efficiency of toluene
      and to investigate the relationship between the adsorption and desorption
      photocatalytic processes. Surface area is an important factor influencing the
      adsorption-photocatalytic efficiency. Higher surface areas of pellets contribute
      to high rates of conversion of toluene. Un-reacted toluene and reaction
      intermediates accumulating on their surface deactivated the titania/silica
      catalyst. To overcome this problem, the adsorption and regeneration process were
      alternated in a dual reactor system. Connecting or disconnecting the toluene feed
      gas enabled one reactor to adsorb toluene, while the second reactor was
      regenerated by photocatalysis. Using UV irradiation and titania/silica pellets
      with high BET surface area (421.1 m2 x g(-1)), the alternating
      adsorption/regeneration processes kept the degradation efficiency of toluene at
      90% after 8 hours operation. By improving the adsorption-photocatalysis
      efficiency, and minimising the generation and accumulation of intermediate on the
      surface of pellets, the method extended catalyst life and maintained a high
      degradation efficiency of toluene.

PMID- 16583819
TI  - Performance evaluation of an agro waste based biofilter treating toluene vapours.
AB  - Biodegradation of toluene vapour was investigated for 162 days in a laboratory
      scale biofilter packed with maize waste. Inlet concentration of toluene was
      varied from 2.86 to 5.79 g m(-3) and the volumetric flow rate of toluene loaded
      air from 0.09 to 0.3 m3 h(-1). The media bed height used in the study was 0.63 m.
      Plug flow behaviour of the bed was confirmed by RTD experiments. The steady state
      was achieved in 18 days. Depending upon initial loading rates, removal efficiency
      ranging from 54.5 to 85.3% and elimination capacity ranging from 43.47 to 174.6 g
      h(-1) m(-3) were observed during steady state operation. The dynamic behaviour of
      the biofilter was evident from response to change in process conditions. The
      stability of the biomass was evident from the fast response of the biofilter to
      shutdown and restart operations. High value of carbon recovery confirms the
      effective biodegradation in the biofilter. In the startup period, the pressure
      drop in the bed increased for some time after that it tended towards a constant
      value.

PMID- 16583821
TI  - The use of bacteriophages for monitoring the microbiological quality of sewage
      sludge.
AB  - The use of bacteriophages as potential indicators of faecal pollution has
      recently been studied. The correlation of the number of bacterial indicators and
      the presence of three groups of bacteriophages, namely somatic coliphages
      (SOMCPH), F-RNA specific phages (FRNAPH) and phages of Bacteroides fragilis
      (BFRPH), in raw and treated sludge is presented in this study. Raw and
      anaerobically digested sewage sludge samples from two wastewater treatment plants
      in Athens were collected on a monthly basis, over a 2-year period, and analyzed
      for total coliforms, E. coli, intestinal enterococci and the three groups of
      bacteriophages. A clear correlation between the number of bacterial indicators
      and the presence of bacteriophages was observed. E. coli concentrations of > or
      =10(3) cfus g(-1) and <10(3) cfus g(-1) comprise a threshold for the presence of
      FRNAPH and BFRPH, respectively. Likewise, intestinal enterococci concentrations
      of > or =10(4) cfus g(-1) and <10(3) cfus g(-1) comprise a threshold for the
      presence of FRNAPH and BFRPH, respectively. In the case of SOMCPH, it was not
      possible to define a threshold, since they were detected with the lowest observed
      indicator concentrations in all samples.

PMID- 16583822
TI  - Characteristics of biofilm community formed in the chlorinated biodegradable
      organic matter-limited tap water.
AB  - The aim of this study was to characterize the influence of free chlorine residual
      on biofilm formation in a chlorinated system in which the biodegradable organic
      matter (BOM) was limited. The biofilm community was characterized through a
      community-level physiological profile (CLPP) that was generated using the Biolog
      GN microplate-based community-level assay. The chlorinated system was run at
      chlorine residual concentrations of 0.3, 0.5, and 1.0 mg l(-1) with the provision
      of BOM-limited tap water (0.01 mg l(-1) as assimilable organic carbon and 0.06 mg
      l(-1) as biodegradable dissolved organic carbon). For comparison, an
      unchlorinated system was operated in parallel under the same condition. The
      number of viable heterotrophic bacteria in the biofilm that formed in the
      chlorinated system over the 3 months of operation averaged 7.2 x 10(3), 4.8 x 10,
      and 1.6 x 10 CFU cm(-2) for the chlorine residual concentrations of 0.3, 0.5, and
      1.0 mg l(-1), respectively. In the unchlorinated system, the average bacterial
      content was 1.1 x 10(6) CFU cm(-2). Using measures of substrate utilization rate,
      substrate utilization diversity, and metabolic potential index (MPI), the CLPP
      patterns demonstrated that the metabolic potentials of the biofilm communities
      decreased markedly as the chlorine residual levels increased. In particular, the
      community level of the biofilm that formed in the system with chlorine residual
      concentration of 1.0 mg l(-1) was the lowest of any biofilm under the tested
      conditions. The results implied that chlorine residual had a positive biocidal
      effect on the metabolic potential and/or functional potential of the biofilm
      community, especially when the BOM level was low. In addition, BOM limitation by
      itself was not sufficient to control biofilm formation.

PMID- 16583824
TI  - Effluent quality of a conventional activated sludge and a membrane bioreactor
      system treating hospital wastewater.
AB  - Two lab scale wastewater treatment plants treating hospital wastewater in
      parallel were compared in terms of performance characteristics. One plant
      consisted of a conventional activated sludge system (CAS) and comprised an anoxic
      and aerobic compartment followed by a settling tank with recycle loop. The second
      pilot plant was a plate membrane bioreactor (MBR). The wastewater as obtained
      from the hospital had a variable COD (Chemical Oxygen Demand) ranging from 250 to
      2300 mg l(-1). Both systems were operated at a similar hydraulic residence time
      of 12 hours. The reference conventional activated sludge system did not meet the
      regulatory standard for effluent COD of 125 mg l(-1) most of the time. Its COD
      removal efficiency was 88%. The plate MBR delivered an effluent with a COD value
      of 50 m g l(-1) or less, and attained an efficiency of 93%. The effluent
      contained no suspended particles. In addition, the MBR resulted in consistent
      operational parameters with a flux remaining around 8-10 l m(-2) h(-1) and a
      trans membrane pressure < 0.1 bar without the need for backwash or chemical
      cleaning. The CAS and the MBR system performed equally well in terms of TAN
      removal and EE2 removal. The CAS system typically decreased bacterial groups for
      about 1 log unit, whereas the MBR decreased these groups for about 3 log units.
      Enterococci were decreased below the detection limit in the MBR and indicator
      organisms such as fecal coliforms were decreased for 1.4 log units in the CAS
      system compared to a 3.6 log removal in the MBR.

PMID- 16583823
TI  - Dechlorination of DDT mediated by bimetallic systems.
AB  - DDT dechlorination efficiencies of bimetallic systems, namely, Mg0-Zn, Mg0-Ni,
      and Mg0-Co were compared. All the systems transformed DDT with efficiencies
      exceeding 98% within 24 h. Based on GC-ECD and GC-MS analyses a step-wise and
      sequential dechlorination of DDT by Mg0-Zn system in 1:1 water acetone phase via
      1,1 dichloro, 2,2- bis (p-chlorophenyl) ethane (DDD), 1, chloro, 2,2 bis (p
      chlorophenyl) ethane (DDMS) to 2,2 bis (p-chlorophenyl) ethane (DDNS) was noted.
      Accumulation of DDNS as the end product indicates that all three alkyl chlorine
      atoms of DDT were removed by Mg0-Zn system. Mg0-Co also showed almost complete
      removal of DDT in water-acetone phase that was accompanied by the accumulation of
      DDD followed by a decline in its concentration as a function of time. On the
      other hand, Mg0-Ni system exhibited inefficient removal of DDT in water-acetone
      phase. In pure acetone phase, Mg0-Co system and Mg0-Ni dechlorinated DDT with the
      accumulation of DDE and DDMU as end products following 24 h of reaction. The
      presence of surfactants or organic solvents is required to ensure solubilization
      of DDT. Also addition of acid is essential to provide sufficient protons for
      efficient reductive dechlorination via hydrogenation. Advantage of Mg0 based
      dehalogenation reactions is that they occur at high rates under ambient
      temperatures, and pressure and oxygen need not be excluded in the reaction phase.
      Our studies revealed that Mg0-Zn is the best option among all tested systems due
      to its high reactivity and low cost, and may be used to treat DDT contaminated
      water.

PMID- 16583825
TI  - Numerical-assisted design of a wind tunnel used in the estimation of
      volatilization from water, waste or soil.
AB  - Numerical simulations of the flow inside two wind tunnel geometries used for
      determining emission volatilization have been conducted. The flow pattern was
      examined in a plane close to the emitting surface. A reduced surface,
      characterizing the low velocity zones in this plane, has been defined. The
      proposed geometry modification, consisting of a convergent/divergent system,
      decreases the low velocity regions by a factor ranging between 2 and 3.5. Large
      vortices present in the conventional configuration are almost eliminated. The new
      velocity distribution, close to the emitting surface, is more uniform and should
      therefore generate a more efficient mass transfer to the flowing air.

PMID- 16583826
TI  - Methodology of management of dredging operations I. Conceptual developments.
AB  - This article presents a new methodology for the management of dredging
      operations. Partly derived from existing methodologies (OECD, UNEP, AIPCN), its
      aim is to be more complete, by integrating the qualities and complementarities of
      former methodologies. Moreover, it was carried out in a context of sustainable
      development. Indeed, it supports, according to a framework of industrial ecology,
      the development and the implementation of solutions of waste improvement of
      dredged materials, in order to minimize the environmental impact of dredging. It
      also uses a tool of MultiCriteria Decision-Making Aid (M.C.D.M.A.), in order to
      integrate local characteristics. In addition, this tool, called DRAGSED, allows
      to a dialogue to be established between all the parties concerned with a dredging
      project (harbour's authorities, industrialists, municipalities, administrations,
      populations, associations,...). Thus, the implementation of this methodology
      enables consensus to be reached for the dredging solution retained. It also
      proposes an environmental follow-up, which will allow an evaluation during its
      application.

PMID- 16583827
TI  - Methodology of management of dredging operations II. Applications.
AB  - This paper presents the new methodology of management of dredging operations.
      Derived partly from existing methodologies (OECD, PNUE, AIPCN), it aims to be
      more comprehensive, mixing the qualities and the complementarities of previous
      methodologies. The application of the methodology has been carried out on the
      site of the Port of Dunkirk (FRANCE). Thus, a characterization of the sediments
      of this site has allowed a zoning of the Port to be established in to zones of
      probable homogeneity of sediments. Moreover, sources of pollution have been
      identified, with an aim of prevention. Ways of waste improvement have also been
      developed, to answer regional needs, from a point of view of competitive and
      territorial intelligence. Their development has required a mutualisation of
      resources between professionals, research centres and local communities,
      according to principles of industrial ecology. Lastly, a tool of MultiCriteria
      Decision-Making Aid (M.C.D.M.A.) has been used to determine the most relevant
      scenario (or alternative, or action) for a dredging operation intended by the
      Port of Dunkirk. These applications have confirmed the relevance of this
      methodology for the management of dredging operations.

PMID- 16583828
TI  - Treatment of landfill leachate by irrigation and interaction with landfill gas.
AB  - The treatment efficiency of landfill leachate irrigation and the effect of
      landfill gas addition were investigated in a vegetated compost/gravel substrate
      by monitoring soil moisture content, drainage water volume and quality in a two
      years lysimeter experiment. Landfill leachate irrigation exceeding 350 mm
      increased soil moisture and drainage volumes owing to the deterioration of the
      vegetation resulting from high sodium chloride inputs. Even so sodium chloride
      was lost in between the irrigation periods, the total reduction of the landfill
      leachate volume by irrigation decreased from 71% in the first year to 38% in the
      second year. Landfill gas addition also increased drainage volumes, but was less
      pronounced. Twenty-two percent of magnesium was retained under landfill leachate
      irrigation, while decreasing pH values, redox potential and high initial
      concentrations in the substrate released calcium, iron and potassium. Ninety
      eight percent of ammonium was removed by irrigation, but 44% of the applied
      ammonium was leached as nitrate after oxidation took place due to a decreased
      uptake after the vegetation deteriorated. Landfill gas fumigation influenced
      landfill leachate treatment by decreasing the redox potential and the pH and
      increasing the drainage water content, which improved the retention of total
      nitrogen and sulfate, but increased the release of iron, calcium and magnesium.
      To conclude, landfill leachate irrigation is a valuable treatment option to
      minimize leachate quantities and remove ammonium independent from the presence of
      landfill gas if salt accumulation is avoided.

PMID- 16583829
TI  - Treatment of recycled carrot washing water.
AB  - Large volumes of effluents and solid waste derive from industrial fresh packing
      and processing of carrots. Due to high organic loads and suspended solids and due
      to insufficient wastewater treatment, surface waters are polluted by effluents of
      carrot washing, as shown for one enterprise in Germany. Over a period of four
      months the water quality was studied at the stages of a treatment system
      consisting of a grit chamber, a settling tank combined with aeration devices and
      a constructed wetland. Organic pollutants were measured as COD and BOD5 in
      different fractions of the wastewater. The daily washing of carrots produces up
      to 300 m3 wastewater with a mean filterable solids content of 453 mg l(-1) and a
      mean COD concentration of 179 mg l(-1). On average the current efficiency of
      total COD reduction is 52%. Due to the fine grain size and the low density of
      suspended solids, settling is very slow and incomplete, primarily during the
      winter. As much as 29 mg COD l(-1) in the effluent derive from the fraction of
      particles which do not settle within 18 hours. The dissolved COD fraction
      accounts for 30 mg l(-1) and reflects the insufficient oxygenation of the
      wastewater. Strategies for enhancing the removal of organic compounds can be
      derived from the results of this study. Spatial separation of settling and
      aeration processes is recommended to optimise the treatment process. Furthermore,
      the area of the constructed wetland should be increased to maintain its hydraulic
      conductivity and to guarantee a high COD reduction.

PMID- 16583830
TI  - [Interview with 10 women with genital human papillomavirus infection].

PMID- 16583831
TI  - [Modification of C3 and C4 levels after the administration of conjugated
      estrogens plus medroxiprogesterone or raloxifene in postmenopausal women].
AB  - OBJECTIVE: To evaluate the effect of conjugated equine estrogens (CEE) plus
      medroxyprogesterone acetate (MPA) and raloxifene on serum levels of complement C3
      and C4 fractions in postmenopausal women. PATIENTS AND METHOD: Twenty healthy
      postmenopausal women were studied. In all weight, height and body mass index
      (BMI) were documented. FSH and estradiol levels were measured. They were randomly
      divided into two groups, according to the treatment they received: group I, CEE
      0.625 mg/day plus MPA 2.5 mg/day (n = 7); group II, raloxifene 60 mg/day (n =
      13), both treatments were continuous. Serum levels of C3 and C4 complement
      fractions were measured by immunonephelometry at baseline and six months after
      start of treatment. Differences among groups of baseline and final C3 and C4
      levels were measured with Student's t test for independent and paired samples,
      respectively. RESULTS: There were no differences among groups in age, weight,
      height and body mass index, neither in C3 and C4 levels among baseline and final
      levels when comparing each group separately. CONCLUSIONS: Complement may not
      intervene significantly in the atherosclerotic inflammatory process in women
      receiving CEE plus MPA or raloxifene.

PMID- 16583832
TI  - [Anorgasmy prevalence in women attended at Familiar Medicine Unit no. 1 in
      Obregon, Sonora, Mexico].
AB  - OBJECTIVE: To estimate the prevalence of anorgasmy in women. PATIENTS AND
      METHODS: An observational, descriptive and transversal study was done from August
      2002 to January 2003 surveying women with sexual activity in a clinic of the
      Mexican Institute of Social Security in Obregon, Sonora. The questionnaire was
      validated by the UNAM. The analyzed variables were: age, scholar degree, the age
      in which women started sexual activity, number of children, marital status, the
      number of sexual partners, pleasure to sex for the women, satisfaction and
      feeling like doing sex, who decides and begins to do sex, frequency of sexual
      intercourse, knowledge about orgasm and one's own experience, as well as
      psychosomatic symptoms. Data were analyzed by descriptive statistics, chi square
      test and Likert's scale. RESULTS: Seventy-three women were surveyed, with ages
      between 16 and 46 years. Anorgasmy frequency was of 6.8%; 53.4% of the women had
      secondary education and 37% superior education. Time of active sexual life varied
      between 1 and 30 years; the knowledge about orgasm was of 74%. CONCLUSIONS: The
      orgasmic dysfunction is lower in this region than that reported in the
      bibliography, this could be due to the greater scholar degree of women, social
      and cultural issues, and the women's independence. Nevertheless, the health team
      must be qualified to detect and treat it, in order to avoid complications.

PMID- 16583833
TI  - [Perception of a group of women about having HPV].
AB  - BACKGROUND: The possibility to acquire sexually transmitted diseases generates
      bio-psycho-social conflicts affecting daily life of women. OBJECTIVE: To
      investigate the knowledge of women on the concept of being infected by the human
      papilloma virus (HPV) and to understand the significance they attributed to their
      condition as HPV carriers. MATERIAL AND METHOD: It is a qualitative study in
      which ten women were interviewed, after the result of a cytopathological exam
      suggesting HPV. Data were collected at the Center of Health School of the
      Universidade Estadual Paulista-UNESP-Brazil. RESULTS: The significant items were:
      deception and preoccupation about the cure, since they indicate that it is very
      deceptive to be infected with an incurable disease by a person whom they trust;
      the method of having sexual relations and being infected again; the necessity of
      care and of being optimistic to face the disease and the threat of cervix cancer
      originating anxiety. DISCUSSION: Orientations made by health professionals were
      efficacious to clarify the relationship with cancer development. It is possible
      to understand the necessity of assistance orientations and the opportunity to
      hear them, offering individualized quality care. This study also offers important
      elements to reinforce the educational role of health professionals, principally
      those referring to sexually transmitted infection and cancer, seeking prevention
      and early treatment with the offered information. However, there is no desire of
      finishing the subject regarding perception, thus there is much to discover about
      diseases related to human papilloma virus.

PMID- 16583834
TI  - [Incidence of infected surgical wound and prophylaxis with cefotaxime in cesarean
      section].
AB  - BACKGROUND: Surgical wound infection after cesarean section varies from 2.5 to
      16.1%, thus the utilization of antibiotic prophylaxis has increased routinely and
      irrationally. Despite this, we can still see cases of infections. OBJECTIVE: To
      determine if the antibiotic prophylaxis with cefotaxime is associated with the
      decreased incidence of wound infection in patients submitted to cesarean section
      without risk factors. PATIENTS AND METHODS: This study was carried out as a
      randomized clinical trial in patients submitted to cesarean section. Two groups
      were formed: in the first group we administered cefotaxime and the other one did
      not receive prophylaxis. The follow-up lasted 30 days to evaluate clinical data
      of infection. RESULTS: We performed 3,300 cesarean in the studied period; 1,000
      patients had the inclusion criteria to participate in the study. A surgical wound
      infection was observed in 31 (0.96%) patients without risk factors. In 14 of
      these patients we administered cefotaxime, and in 17 patients we did not use
      prophylaxis. The highest frequency of infection was observed in the group of 24
      to 30 years old, with 16 patients (51.6%). The clinical data of infection were:
      dehiscence in 29 patients (93.5%), pus secretion in 23 (74.2%), and fever in only
      3 (9.7%) of them. The hospital stay after the infection was of five days in 75%
      of the cases. When the use of cefotaxime as prophylaxis was analyzed in both
      groups we had an odds ratio of 0.82, which was not significant. DISCUSSION: The
      use of cefotaxime in patients operated of cesarean does not have great
      transcendence since it does not reduce the infection incidence. The use of
      antibiotics in an irrational way implies a high cost, since the majority of the
      post-operation infections are not complicated, involving exclusively the skin and
      cellular subcutaneous tissue. Then, the cases with risk factors should be
      analyzed carefully for the cefotaxime administration.

PMID- 16583835
TI  - [Effect of maternal diabetes on human and rat fetal development].
AB  - Diabetes is a genetically determined metabolic disease with fasting hyperglycemia
      due to relative or absolute absence of insulin. With the use of exogenous
      insulin, successful gestations are now possible. Nevertheless, there are still
      severe problems associated, such as spontaneous abortion, perinatal mortality and
      congenital malformations. Caudal regression syndrome, disclosure of the neural
      tube and cardiovascular alterations are the most common malformations.
      Gestational diabetes can induce increased fetal corporal fat and macrosomia with
      hyperinsulinemia, hypoglycemic, hypoxia, metabolic acidosis and perinatal death.
      During adult life, diabetic mothers' children can develop obesity, glucose
      intolerance and type 2 diabetes. In order to study fetuses' alterations during
      diabetic gestations we now have animal models of diabetes. Maternal diabetes in
      rats alters fetal development in a very similar manner to that of humans.
      Although we do not accurately know the pathogenic mechanism by which diabetes
      produces fetuses' abnormal development, hyperglycemia and hyperketonemia had been
      mentioned to have predominant roles. Hyperglycemia damages DNA and increases
      oxidative stress and hyperketonemia increases the rate of embryo malformations.
      The addition of antioxidants such as C and E vitamins can reduce this damage.
      During adult life, diabetic rats' cubs have alterations in glucose metabolism and
      in reproductive function. The understanding of mechanisms by which maternal
      diabetes affects fetuses development, can help us to prevent complications and
      improve mothers' and children's life quality.

PMID- 16583836
TI  - [Assertive medicine: a proposal against defensive medicine].
AB  - More than ever the physician-patient relationship is deteriorated by diverse
      factors, among these liability complaints stand out, and have propitiated the
      practice of defensive medicine, an attitude considered in many countries as
      inappropriate, expensive and unethical. Defensive medicine widens the distance
      between a physician and his patient. To revert this vice and its noxious effects
      which corrupt the patient-physician relationship in our country, we propose that
      physicians put to practice actions which permit the renewal of the essence of
      humanistic medicine in their daily practice and the restoration of the
      relationship. These changes in attitude sum up to a proposition of professional
      practice which we have denominated assertive medicine. This offer is resumed in
      four points: 1) Maintain a proper verbal and non verbal communication with each
      patient, 2) Keep continuously up to date skills, knowledge and abilities, 3)
      Respect the patient's rights and 4) Defend their own rights as physicians.

PMID- 16583837
TI  - [Acute pulmonary edema secondary to acute myocardial infarction during
      transoperatory of cesarean section].
AB  - It is a clinic case of an eighteen year-old woman without risk factors, with 40
      weeks of pregnancy in labor and fetal heart failure who became to cesarean
      section. Taking in account our results we can argue that she presented acute
      pulmonary edema and subendocardic ischemia of the after wall and lateral.
      Diagnosis should be based on the clinical finding, the electrocardiogram, chest
      film and corroborated with laboratory. Early diagnosis and treatment
      significantly reduce morbimortality rates.

PMID- 16583838
TI  - [Giant uterine myoma].
AB  - Giant uterine tumors, defined as weighing 11.4 kg (25 lb) or more, are uncommon.
      The last cases reported were published on May, 2003 by Oelsner and collaborators.
      We report the case of a 45-year old woman with a large abdominal mass and three
      day history of constipation and respiratory difficulty. Total abdominal
      hysterectomy and bilateral salpingo-oophorectomy was performed, and a giant
      uterine myoma, which weighted 12.4 kg (27.3 lb), was found. The patient's
      postoperative course was uneventful and she was discharged on the fourth
      postoperative day.

PMID- 16583839
TI  - [Genital prolapse treatment. Regional criterion and experience. 1950].

PMID- 16583840
TI  - [Infiltrating lobular carcinoma of the breast: clinical stage, radiological and
      histological features].
AB  - BACKGROUND: The characteristics of the infiltrating lobular carcinoma of the
      breast are not clear, this is caused by special histological and biological
      features. OBJECTIVE: To identify the clinical stage and correlate it with the
      radiological and histological features of the disease to make an opportune
      diagnosis. PATIENTS AND METHODS: From January 1st, 2003 to July 31st, 2004 we
      identified 68 cases of infiltrating lobular carcinoma at the Luis Castelazo Ayala
      Hospital. The cases were classified by clinical, radiological and histological
      features. The results were expressed in media and standard deviation. The
      difference between the mixed and pure lobular carcinoma types were compared by
      chi-square test. RESULTS: From 68 patients, 31 had mixed lobular carcinoma, 20
      pure, 12 were eliminated because the patient's records were not found and five
      because the definitive histological report was not lobular carcinoma. The median
      age for both groups was 50 years old. The most affected region was the upper one
      (> 80%). The hormonal receptor was more frequently expressed in the pure subtype
      (p < 0.04), this latter was associated to a delayed diagnosis (p < 0.03).
      Mammography was considered useful for diagnosis. CONCLUSIONS: The histological
      behavior of lobular carcinoma is related to non clear characteristics and to
      delayed diagnosis; however, with a careful evaluation these features can be
      recognized and make possible an opportune mammography.

PMID- 16583841
TI  - [Overuse of colposcopy service in Mexico].
AB  - BACKGROUND: Cervicouterine cancer is one of the main public health problems in
      Mexico. Several problems related to the low effectiveness of the Program of
      Opportune Detection of Cervicouterine Cancer have been identified, among them:
      low cover of the disease detection and absence of quality control in the
      detection, diagnosis and treatment of it. In Mexico the quality control problem
      in cytology has been taken with success, but the opposite occurs with colposcopy
      practice. For that reason this service is overused by patients with low risk
      cancer and is not accessible for the high risk population. OBJECTIVE: To evaluate
      the association between cervicouterine cancer knowledge and satisfaction with the
      service regarding the use and intention of adherence to it for the follow-up and
      treatment, as well as analyze the resources used for this attention. PATIENTS AND
      METHODS: A transversal study was done from May to December, 2002. It included all
      the patients who went to the Colposcopy Service in three hospitals. 1,606
      patients were interviewed, from them 443 cases were first-time visits and 1,163
      were subsequent ones. RESULTS: In a multivariate model we observed that the real
      utility knowledge of cervicovaginal cytology increases the probability that women
      come back to the Colposcopy Service (OR 2.0, Cl 95%: 1.57, 2.54). Patients who
      know their diagnosis when it is dysplasia or cancer are more likely to become
      attached to their follow-up than those who do not know it. 91% of the users
      (1,463) had two or more cervicovaginal cytolgies done, and 49% (787) had eight or
      more. Patients who know the purpose and utility of the biopsy had a 4.4 fold
      probability of become subsequent than those that do not know such information (Cl
      95%: 1.72 to 11.35). CONCLUSIONS: Nowadays colposcopy clinics treat 70% of the
      patients who are subsequent and that have normal reports of cytology. This shows
      us an overuse of the service, with the consequent service, monetary and
      opportunity costs for women. More studies should be done to reformulate the rule
      that controls the treatment of these patients, and incorporate follow-up
      guidelines according to the natural history of the disease in Mexican women.

PMID- 16583842
TI  - [Prevalence of Streptococcus agalactiae colonization in pregnant women at term].
AB  - OBJECTIVE: To determine the prevalence of colonization by Streptococcus
      agalactiae in pregnant women at term. MATERIAL AND METHODS: We carried out a
      cross-sectional study. Four hundred thirty three pregnant patients at term
      without data of cervicovaginitis were included. We processed vaginal and rectal
      swabs with hisopo placed in the Stuart middle of transport. They were inoculated
      on blood agar with nalidixic acid and gentamicine incubating itself by duplicate
      on Todd-Hewitt broth. The samples with suggestive result were reincubating to
      detect suspicious Streptococcus using the CAMP test, for final identification.
      Some clinical variables were included as age, gravidity, parity, abortions,
      cesarean sections, and vaginal infections during pregnancy. RESULTS: We found two
      patients with positive result for Streptococcus agalactiae in vaginal swabs that
      represented a prevalence of 0.46%; in those cases therapeutic measures were
      provided for both mother and newborn. The mean age for patients was 27 years. The
      median value for gravidity was 2, for parity was 1; and for spontaneous abortions
      and cesarean sections were 0, respectively. In our studied women 77.8% of them
      referred previous unspecified vaginal infections. CONCLUSIONS: In our setting the
      prevalence of Streptococcus agalactiae colonization in pregnant women at term is
      low. Due to morbidity associated to this infection, it is suggested the specific
      research of this microorganism both in pregnant women and in their newborns.

PMID- 16583843
TI  - [Current colposcopic terminology. Successes and limitations].
AB  - Colposcopy is nowadays a habitual tool applied to the routine gynecological
      exploration. The terminology for the normal and abnormal colposcopic findings has
      changed according with the time and the new knowledge about the low genital tract
      diseases. Gynecologists must be aware of this terminology for a correct
      application in diagnosis, therapeutics and papers on findings and results. It is
      necessary that the whole medical community around the world applies the same
      terminology in order to have a better communication.

PMID- 16583844
TI  - [Complicated pregnancy with lithiasis and resectable gallbladder cancer. A case
      report and literature review].
AB  - Pregnancy complicated with gallbladder disease stone has an incidence of 2-14%,
      and more than 30% of patients do not respond to medical treatment; therefore, in
      order to reduce the morbidity and mortality in fetus and mother, surgical
      management would be required. The current use of ultrasound of high resolution
      has facilitated the diagnosis and also, in the present clinical case, this
      imaging modality allowed us to suspect the unusual diagnosis reported, that
      corresponds to a female of 34 years old with 33 weeks of pregnancy, complicated
      with symptomatic gallbladder disease stone, whose pain was intractable at the
      expectant management. The clinical diagnosis was corroborated by ultrasound and
      the report was: lithiasis, biliary sludge and an intragallbladder image of
      bilobular polypoid. The patient was submitted to cholecystectomy by laparotomy,
      whose histopathologic findings were: cholelithiasis and in situ gallbladder
      adenocarcinoma with an exophytic growing variety. The purposes of this article
      are to report a case and to review the literature.

PMID- 16583845
TI  - [Vagina cancer in a young woman exposed to diethylstilbestrol: case report and
      literature review].
AB  - We analyzed a 20 year-old patient case exposed in utero to diethylstilbestrol, as
      probably predisposed factor in vaginal cancer. The histopathological report of
      the incisional biopsy was clear cell vaginal adenocarcinoma, stage III,
      widespread to the pelvic wall, with metastasis to regional lymph nodes, and lack
      of distant metastasis. We decided surgical management: protocolized laparotomy,
      peritoneal washing, retroperitoneal node biopsies and a radical hysterectomy,
      Piver III, with two thirds parts of vagina. By poor prognosis we decided to offer
      an adjuvant management, with systemic chemotherapy.

PMID- 16583846
TI  - [Abdominal surgery, pregnancy and delivery. 1950].

PMID- 16583847
TI  - Barriers to entrepreneurship in healthcare organizations.
AB  - Entrepreneurship has received little attention in the healthcare industry,
      perhaps in part because of barriers inherent in the structure and culture of
      healthcare organizations. Eliminating barriers can help promote entrepreneurial
      activities to drive continuing innovation and identify new sources of revenue.

PMID- 16583848
TI  - Health care entrepreneurship: financing innovation.
AB  - Entrepreneurship is often described as the ability to create new ventures from
      new or existing concepts, ideas and visions. There has been significant
      entrepreneurial response to the changes in the scientific and social
      underpinnings of health care services delivery. However, a growing portion of the
      economic development driving health care industry expansion is threatened further
      by longstanding use of financing models that are suboptimal for health care
      ventures. The delayed pace of entrepreneurial activity in this industry is in
      part a response to the general economy and markets, but also due to the lack of
      capital for new health care ventures. The recent dearth of entrepreneurial
      activities in the health services sector may also due to failure to consider new
      approaches to partnerships and strategic ventures, despite their mutually
      beneficial organizational and financing potential. As capital becomes more scarce
      for innovators, it is imperative that those with new and creative ideas for
      health and health care improvement consider techniques for capital acquisition
      that have been successful in other industries and at similar stages of
      development. The capital and added expertise can allow entrepreneurs to leverage
      resources, dampen business fluctuations, and strengthen long term prospects.

PMID- 16583849
TI  - Entrepreneurship management in health services: an integrative model.
AB  - This research develops an integrated systems model of entrepreneurship management
      as a method for achieving health care organizational survival and growth.
      Specifically, it analyzes current health care environment challenges, identifies
      roles of managers and discusses organizational theories that are relevant to the
      health care environment, outlines the role of entrepreneurship in health care,
      and describes the entrepreneurial manager in the entrepreneurial management
      process to produce desirable organizational outcomes. The study concludes that as
      current health care environment continues to show intense competition,
      entrepreneurial managers are responsible for creating innovations, managing
      change, investing in resources, and recognizing opportunities in the environment
      to increase organizational viability.

PMID- 16583850
TI  - Entrepreneurial organizations: the driving force for improving quality in the
      healthcare industry.
AB  - Using DiMaggio and Powell's concept of institutional isomorphism, the authors
      explain why healthcare lags behind other industries in innovating new production
      functions that address quality. Healthcare finns can "learn" to be
      entrepreneurial organizations within Stevenson's 'entrepreneurial versus
      administrative behavior' framework and Covin and Slevin's model of an
      entrepreneurial organization's required culture and behavioral support structure.

PMID- 16583851
TI  - A diagnostic approach to understanding entrepreneurship in health care.
AB  - Health care is quite different from other industries because of its
      organizational structure, service delivery, and financing of health services.
      Balancing costs, quality, and access presents unique challenges for each
      stakeholder group committed to promoting the health and healing of its citizens.
      Using the diagnostic approach to health care entrepreneurship, we created a
      framework from research in the field to understand the predisposing, enabling,
      and reinforcing factors most relevant to successful entrepreneurship.

PMID- 16583852
TI  - Is it doom, gloom or boom?

PMID- 16583853
TI  - Minister discusses the future of maternity services.

PMID- 16583854
TI  - Conjoined twins: the ethics of separation.

PMID- 16583855
TI  - Preterm birth: a medical miracle with an emotional cost?

PMID- 16583856
TI  - PDFs judged a great success.

PMID- 16583857
TI  - One step at a time: progress in Powys.

PMID- 16583858
TI  - Guide for student midwives undertaking overseas elective experience.

PMID- 16583859
TI  - A midwifery trust?

PMID- 16583861
TI  - Midwives: magpies or mice?

PMID- 16583860
TI  - Are you normal? Implementing normality in the maternity unit.

PMID- 16583863
TI  - Should primigravid women with low-risk pregnancies have the right to choose an
      elective caesarean section?

PMID- 16583862
TI  - What price for a perfect delivery?

PMID- 16583864
TI  - 'Anxiety and disbelief' as DoH fiascoo scuppers business plans.

PMID- 16583865
TI  - Market regulation. When will ministers allow foundation trusts to fail?

PMID- 16583866
TI  - On paying for the White Paper.

PMID- 16583867
TI  - Data briefing. Emergency admissions.

PMID- 16583868
TI  - Payment by results. How to steer clear of PbR gaming.

PMID- 16583869
TI  - Media portrayals of nurses: what can we do?

PMID- 16583870
TI  - Childhood sexual abuse affects future relationships.

PMID- 16583871
TI  - Principles & practice of polypharmacotherapy.

PMID- 16583872
TI  - Health literacy in older adults.
AB  - Health literacy is a critical goal for nurses to address. Consider the patient
      who stated: They told me I was taking double the medication I was supposed to. I
      had two bottles, and I was taking one from each bottle, but it turned out they
      were the same medication. But since I didnt know how to read. I didn't know.
      (University of Virginia Health Systems, 2003). Many older adults struggle daily
      to manage their health care problems; compounding these dificulties with low
      literacy skills can be devastating. They need our help.

PMID- 16583873
TI  - Detecting suicide risk in adolescents and adults in an emergency department: a
      pilot study.
AB  - The investigators conducted a pilot study to detect suicide risk in adolescents
      and adults seeking treatment in an emergency department, as well as to test the
      reliability and validity of the 4-item Risk of Suicide Questionnaire (RSQ). This
      study expanded the implementation of the RSQ beyond its initial use with children
      and adolescents with psychiatric symptoms who were seeking treatment in a
      pediatric emergency department to include adolescent and adult patients in a
      Level I trauma center. An advanced practice psychiatric nurse verbally
      administered the RSQ to a convenience sample of 104 emergency department patients
      ages 12 to 82. Psychometric analysis demonstrated an adequate degree of
      reliability and criterion-related validity for the RSQ. Approximately 30% of all
      patients who participated screened positive for suicide risk. The results support
      the continued use of the 4-item RSQ with all adolescents and use of a reduced 2
      item form of the RSQ with adults exhibiting psychiatric chief complaints to
      determine imminent risk of suicide in patients who seek treatment in the
      emergency department. Nurses in all health care settings need to initiate suicide
      screening and implement nursing interventions directed toward suicide prevention.

PMID- 16583874
TI  - Standardizing the care of detox patients to achieve quality outcomes.
AB  - Providing appropriate treatment for detoxification patients is both challenging
      and difficult because alcohol abuse and dependence are largely underestimated in
      the acute hospital setting. Alcohol withdrawal syndrome is treated not only by
      addictionologists on chemical dependency units, but also by primary care
      physicians in acute inpatient settings. The need for consistent inpatient
      treatment through the use of identified protocols can help provide safe and
      effective care. The need for consistent, inpatient medical-surgical
      detoxification treatment in our organization became apparent with the staff's
      identification of patient care concerns. Using an organizational approach, a
      multidisciplinary team was created to standardize the care of detoxification
      patients, beginning with patient admission and ending with discharge and referral
      for outpatient management. Standardization would ensure consistent assessment and
      intervention, and improve communication among the clinical team members. A
      protocol was developed for both the emergency department and the inpatient units.
      The goals of the team were to decrease the adverse events related to
      detoxification, such as seizures and aggression, and provide a consistent method
      of treatment for staff to follow.

PMID- 16583875
TI  - Needs of families affected by mental illness.
AB  - 1. To obtain the best outcomes for clients with mental illnesses, the needs of
      their families must also be assessed and addressed. One basic need is
      information. 2. Nurses can effectively teach clients and families many skills,
      including problem solving, parenting, coping with daily living and personal and
      family stressors, and effective communication. 3. Referring families to
      appropriate outside resources can provide them with a means of continuing
      support.

PMID- 16583877
TI  - Effect of masker-fringe onset asynchrony on overshoot (L).
AB  - The study examines how overshoot is influenced by masker-signal onset asynchrony
      when the masker contains frequencies above or below the signal frequency. Masked
      thresholds were measured for a 2-ms tone at 5 kHz. The measurements were made in
      a reference condition with a narrow center-band (CB) noise masker (4590-5464 Hz),
      and in conditions with either a low-fringe (1900-4590 Hz) or a high-fringe noise
      band (5500-11 000 Hz) added to the CB. The signal always came on 2 ms after the
      onset of the CB. The time interval, between fringe and signal onsets varied from 
      98 ms (signal onset before fringe onset) to +502 ms (signal onset after fringe
      onset). Results show that overshoot is largest, 8-11 dB, for a high fringe with
      onset occurring between 8 ms before the signal onset and 12 ms after it. Thus,
      pronounced overshoot is observed even when the high fringe is gated on after the
      signal's offset. Low fringes produce no more than 4 dB of overshoot, much less
      than high fringes produce. The finding of pronounced overshoot elicited by a high
      fringe presented shortly after the end of the signal suggests that overshoot is
      governed, at least in part, by central mechanisms.

PMID- 16583887
TI  - Cost-effective assembly of a basic fiber-optic hydrophone for measurement of high
      amplitude therapeutic ultrasound fields.
AB  - Design considerations, assembly details, and operating procedures of one version
      of a cost-effective basic fiber-optic probe hydrophone (FOPH) are described in
      order to convey practical information to groups interested in constructing a
      similar device. The use of fiber optic hydrophones can overcome some of the
      limitations associated with traditional polyvinylidene difluoride (PVDF)
      hydrophones for calibration of acoustic fields. Compared to standard PVDF
      hydrophones, FOPH systems generally have larger bandwidths, enhanced spatial
      resolution, reduced directionality, and greater immunity to electromagnetic
      interference, though they can be limited by significantly lower sensitivities.
      The FOPH system presently described employs a 100-microm multimode optical fiber
      as the sensing element and incorporates a 1-W laser diode module, 2 x 2 optical
      coupler, and general-purpose 50-MHz silicon p-i-n photodetector. Wave forms
      generated using the FOPH system and a reference PVDF hydrophone are compared, and
      intrinsic and substitution methods for calibrating the FOPH system are discussed.
      The voltage-to-pressure transfer factor is approximately 0.8 mV/MPa (-302 dB re 1
      V/microPa), though straightforward modifications to the optical components in the
      FOPH system are discussed that can significantly increase this value.
      Recommendations are presented to guide the choice of optical components and to
      provide practical insight into the routine usage of the FOPH device.

PMID- 16583898
TI  - The relation between electrophysiologic channel interaction and electrode pitch
      ranking in cochlear implant recipients.
AB  - The primary goal of this study was to examine the relation between
      electrophysiologic measures of channel interaction and the ability to
      discriminate pitch between electrodes in a psychophysical pitch-ranking task. It
      was hypothesized that cochlear implant recipients should perform better on an
      electrode pitch-ranking task when using electrodes with less channel interaction
      as measured with the electrically evoked compound action potential (ECAP). The
      width of the ECAP channel interaction function was compared with the slope of the
      pitch-ranking function for 10 adult Nucleus 24 recipients. Results showed no
      significant correlation between electrode pitch-ranking ability and width of the
      ECAP channel interaction function for individual subjects or for group data.
      Additionally, there was no significant correlation between speech perception
      performance and either pitch-ranking ability or width of the ECAP channel
      interaction function. These results suggest that the width of the ECAP
      interaction function may not be an accurate predictor of the ability to
      discriminate between electrodes on the basis of pitch.

PMID- 16583899
TI  - Electrophysiologic channel interaction, electrode pitch ranking, and behavioral
      threshold in straight versus perimodiolar cochlear implant electrode arrays.
AB  - The primary goal of this study was to examine electrophysiologic measures of
      channel interaction, electrode pitch discrimination ability using a pitch-ranking
      task, and behavioral threshold levels in individuals implanted with a straight
      electrode array versus a perimodiolar array. It was hypothesized that
      perimodiolar arrays should yield lower thresholds, less channel interaction as
      measured with the electrically evoked compound action potential (ECAP), and
      better electrode pitch-ranking ability. Results from ten adult Nucleus 24
      recipients (N=5 straight array, N=5 perimodiolar Contour array) showed no
      significant difference in threshold between the two electrode designs; however,
      there was significantly better electrode pitch-ranking ability and less channel
      interaction as measured with the ECAP for perimodiolar electrodes. Additionally,
      there was a significant positive correlation between behavioral threshold and
      width of the ECAP interaction function for Contour group data. There was no
      significant correlation between behavioral threshold and electrode pitch-ranking
      ability. These data suggest that electrode design and/or perimodiolar position
      may reduce physiologic channel interaction in the cochlea and improve electrode
      pitch discrimination ability; however, this positive finding did not translate
      into significantly better speech perception ability for Contour subjects.

PMID- 16583900
TI  - Auditory evoked potentials in females with high and low acceptance of background
      noise when listening to speech.
AB  - Acceptable noise level (ANL) is a measure of a listener's acceptance of
      background noise when listening to speech. A consistent finding in research on
      ANL is large intersubject variability in the acceptance of background noise. This
      variability is not related to age, gender, hearing sensitivity, type of
      background noise, speech perception in noise performance, cochlear responses, or
      efferent activity of the medial olivocochlear pathway. In the present study,
      auditory evoked potentials were examined in 21 young females with normal hearing
      with low and high acceptance of background noise to determine whether differences
      in judgments of background noise are related to differences measured in aggregate
      physiological responses from the auditory nervous system. Group differences in
      the auditory brainstem response, auditory middle latency response, and cortical,
      auditory late latency response indicate that differences in more central regions
      of the nervous system account for, at least in part, the variability in
      listeners' willingness to accept background noise when listening to speech.

PMID- 16583901
TI  - A glimpsing model of speech perception in noise.
AB  - Do listeners process noisy speech by taking advantage of "glimpses"
      spectrotemporal regions in which the target signal is least affected by the
      background? This study used an automatic speech recognition system, adapted for
      use with partially specified inputs, to identify consonants in noise. Twelve
      masking conditions were chosen to create a range of glimpse sizes. Several
      different glimpsing models were employed, differing in the local signal-to-noise
      ratio (SNR) used for detection, the minimum glimpse size, and the use of
      information in the masked regions. Recognition results were compared with
      behavioral data. A quantitative analysis demonstrated that the proportion of the
      time-frequency plane glimpsed is a good predictor of intelligibility. Recognition
      scores in each noise condition confirmed that sufficient information exists in
      glimpses to support consonant identification. Close fits to listeners'
      performance were obtained at two local SNR thresholds: one at around 8 dB and
      another in the range -5 to -2 dB. A transmitted information analysis revealed
      that cues to voicing are degraded more in the model than in human auditory
      processing.

PMID- 16583902
TI  - Estimates of effective frequency selectivity based on the detection of a tone
      added to complex maskers.
AB  - In Experiment 1, the validity of parameters associated with the roex(p, r)
      auditory filter shape was examined for three different types of maskers: (a) A
      noise masker, (b) a random 12-tone masker whose frequencies varied on a burst-by
      burst basis [multiple-burst different (MBD)], and (c) a random 12-tone masker
      whose frequencies were the same across bursts [multiple-burst same (MBS)]. First,
      the power spectrum model of masking was used to estimate auditory filter shapes
      for four observers. Second, the resulting auditory filter shapes were used in a
      computer simulation that provided an estimate of internal noise for each
      observer. Third, relative weights across frequency were estimated for each
      observer and each masker type. For the noise masker, these analyses provided
      predictions and relative weights that were consistent across the three analyses.
      For the MBD and MBS maskers, there was little consistency; neither the estimated
      internal noise nor the estimated relative weights reliably supported a single
      filter model of detection. In Experiment 2, the time course for the detection of
      a tone added to an MBD masker was evaluated by estimating relative weights
      jointly in time and frequency. The relative weights at the signal frequency
      formed a rough inverse "U" across time.

PMID- 16583903
TI  - Using monkeys to explore perceptual "loss" versus "learning" models in English
      and Spanish voice-onset-time perception.
AB  - Cross-language research using synthetic voice-onset-time series over the past 40
      years suggests that the Spanish lead contrast is acoustically less salient than
      the English lag contrast. This study examined monkey identification of a labial
      consonant-vowel voice-onset-time (CV VOT) series (-60 to +70 ms) in order to
      obtain a linguistically unbiased estimate of lead versus lag salience.
      Comparisons were made with both English and Spanish adult human listeners. In a
      classic two-choice identification test, monkey and Spanish functions were quite
      variable and showed evidence of sensitivity to three types of voicing cues (lead
      versus simultaneous versus lag). In contrast, English functions were highly
      categorical and showed sensitivity to only two types of cues (combined
      lead/simultaneous versus lag). Next, listeners were explicitly trained via
      feedback to differentiate stimuli crossing lead and lag boundaries. Here, monkey
      and Spanish performance was initially more symmetrical than English performance,
      with the latter showing reduced sensitivity to the lead boundary, but group
      differences disappeared after extended training. These results provide evidence
      for perceptual loss in English listeners for aspects of Spanish voicing lead
      perception.

PMID- 16583904
TI  - Release from speech-on-speech masking by adding a delayed masker at a different
      location.
AB  - The amount of masking exerted by one speech sound on another can be reduced by
      presenting the masker twice, from two different locations in the horizontal
      plane, with one of the presentations delayed to simulate an acoustical
      reflection. Three experiments were conducted on various aspects of this
      phenomenon. Experiment 1 varied the number of masking talkers from one to three
      and the signal-to-noise (S/N) ratio from -12 to +4 dB. Evidence of masking
      release was found for every combination of these variables tested. For the most
      difficult conditions (multiple maskers and negative S/N) the amount of release
      was approximately 10 dB. Experiment 2 varied the timing of leading and lagging
      masker presentations over a broad range, to include shorter delay times where
      room reflections of speech are rarely noticed by listeners and longer delays
      where reflections can become disruptive. Substantial masking release was found
      for all of the shorter delay times tested, and negligible release was found at
      the longer delays. Finally, Experiment 3 used speech-spectrum noise as a masker
      and searched for possible energetic masking release as a function of the lead-lag
      time delay. Release of up to 4 dB was found whenever delays were 2 ms or less. No
      energetic masking release was found at longer delays.

PMID- 16583905
TI  - Effects of reverberation and masking on speech intelligibility in cochlear
      implant simulations.
AB  - Two experiments investigated the impact of reverberation and masking on speech
      understanding using cochlear implant (CI) simulations. Experiment 1 tested
      sentence recognition in quiet. Stimuli were processed with reverberation
      simulation (T=0.425, 0.266, 0.152, and 0.0 s) and then either processed with
      vocoding (6, 12, or 24 channels) or were subjected to no further processing.
      Reverberation alone had only a small impact on perception when as few as 12
      channels of information were available. However, when the processing was limited
      to 6 channels, perception was extremely vulnerable to the effects of
      reverberation. In experiment 2, subjects listened to reverberated sentences,
      through 6- and 12-channel processors, in the presence of either speech-spectrum
      noise (SSN) or two-talker babble (TTB) at various target-to-masker ratios. The
      combined impact of reverberation and masking was profound, although there was no
      interaction between the two effects. This differs from results obtained in
      subjects listening to unprocessed speech where interactions between reverberation
      and masking have been shown to exist. A speech transmission index (STI) analysis
      indicated a reasonably good prediction of speech recognition performance. Unlike
      previous investigations, the SSN and TTB maskers produced equivalent results,
      raising questions about the role of informational masking in CI processed speech.

PMID- 16583906
TI  - A comparison of adaptive procedures for rapid and reliable threshold assessment
      and training in naive listeners.
AB  - In psychoacoustic studies there is often a need to assess performance indices
      quickly and reliably. The aim of this study was to establish a quick and reliable
      procedure for evaluating thresholds in backward masking and frequency
      discrimination tasks. Based on simulations, four procedures likely to produce the
      best results were selected, and data collected from 20 naive adult listeners on
      each. Each procedure used one of two adaptive methods (staircase or maximum
      likelihood estimation, each targeting the 79% correct point on the psychometric
      function) and two response paradigms (3-interval, 2-alternative forced-choice AXB
      or 3-interval; 3-alternative forced-choice oddball). All procedures yielded
      statistically equivalent threshold estimates in both backward masking and
      frequency discrimination, with a trend to lower thresholds for oddball procedures
      in frequency discrimination. Oddball procedures were both more efficient and more
      reliable (test-retest) in backward masking, but all four procedures were equally
      efficient and reliable in frequency discrimination. Fitted psychometric functions
      yielded similar thresholds to averaging over reversals in staircase procedures.
      Learning was observed across threshold-assessment blocks and experimental
      sessions. In four additional groups, each of ten listeners, trained on the
      different procedures, no differences in performance improvement or rate of
      learning were observed, suggesting that learning is independent of procedure.

PMID- 16583908
TI  - Fundamental frequency of infants' and parents' utterances in longitudinal
      recordings.
AB  - The fundamental frequencies (F0) of daily life utterances of Japanese infants and
      their parents from the infant's birth until about 5 years of age were
      longitudinally analyzed. The analysis revealed that an infant's F0 mean decreases
      as a function of month of age. It also showed that within- and between-utterance
      variability in infant F0 is different before and after the onset of two-word
      utterances, probably reflecting the difference between linguistic and
      nonlinguistic utterances. Parents' F0 mean is high in infant-directed speech
      (IDS) before the onset of two-word utterances, but it gradually decreases and
      reaches almost the same value as in adult-directed speech after the onset of two
      word utterances. The between-utterance variability of parents' F0 in IDS is large
      before the onset of two-word utterances and it subsequently becomes smaller. It
      is suggested that these changes of parents' F0 are closely related to the
      feasibility of communication between infants and parents.

PMID- 16583907
TI  - Effects of auditory feedback on fricatives produced by cochlear-implanted adults
      and children: acoustic and perceptual evidence.
AB  - Acoustic analyses and perception experiments were conducted to determine the
      effects of brief deprivation of auditory feedback on fricatives produced by
      cochlear implant users. The words /si/ and /Si/ were recorded by four children
      and four adults with their cochlear implant speech processor turned on or off. In
      the processor-off condition, word durations increased significantly for a
      majority of talkers. These increases were greater for children compared to
      adults, suggesting that children may rely on auditory feedback to a greater
      extent than adults. Significant differences in spectral measures of /S/ were
      found between processor-on and processor-off conditions for two of the four
      children and for one of the four adults. These talkers also demonstrated a larger
      /s/-/S/ contrast in centroid values compared to the other talkers within their
      respective groups. This finding may indicate that talkers who produce fine
      spectral distinctions are able to perceive these distinctions through their
      implants and to use this feedback to fine tune their speech. Two listening
      experiments provided evidence that some of the acoustic changes were perceptible
      to normal-hearing listeners. Taken together, these experiments indicate that for
      certain cochlear-implant users the brief absence of auditory feedback may lead to
      perceptible modifications in fricative consonants.

PMID- 16583909
TI  - Loud speech over noise: some spectral attributes, with gender differences.
AB  - In seeking an acoustic description of overloaded voice, simulated environmental
      noise was used to elicit loud speech. A total of 23 adults, 12 females and 11
      males, read six passages of 90 s duration, over realistic noise presented over
      loudspeakers. The noise was canceled out, exposing the speech signal to analysis.
      Spectrum balance (SB) was defined as the level of the 2-6 kHz band relative to
      the 0.1-1 kHz band. SB averaged across many similar vowel segments became less
      negative with increasing sound pressure level (SPL), as described in the
      literature, but only at moderate SPL. At high SPL, SB exhibited a personal
      "saturation" point, above which the high-band level no longer increased faster
      than the overall SPL, or even stopped increasing altogether, on average at 90.3
      dB (@30 cm) for females and 95.5 dB for males. Saturation occurred 6-8 dB below
      the personal maximum SPL, regardless of gender. The loudest productions were
      often characterized by a relative increase in low-frequency energy, apparently in
      a sharpened first formant. This suggests a change of vocal strategy when the high
      spectrum can rise no further. The progression of SB with SPL was
      characteristically different for individual subjects.

PMID- 16583910
TI  - Functional data analysis of prosodic effects on articulatory timing.
AB  - An application of functional data analysis (FDA) (Ramsay and Silverman, 2005,
      Functional Data Analysis, 2nd ed. (Springer-Verlag, New York)) for linguistic
      experimentation is explored. The functional time-registration method provided by
      FDA is shown to offer novel advantages in the investigation of articulatory
      timing. Traditionally, articulatory studies examining the effects of linguistic
      variables such as prosody on articulatory timing have relied on comparing the
      durations of speech intervals of interest defined by kinematic landmarks. Such
      measurements, however, do not preserve information on the detailed, continuous
      pattern of articulatory timing that unfolds during these intervals. We present an
      approach that allows the analysis of entire, continuous kinematic trajectories
      obtained in a movement tracking experiment examining the influence of a phrasal
      boundary on articulatory patterning. FDA time deformation functions, after
      alignment of test and reference (control) signals, reveal delaying of articulator
      movement (i.e., slowing of the internal clock rate) in the presence of a phrase
      boundary as the speech stream recedes from the boundary. This is a theoretically
      predicted pattern (Byrd and Saltzman, 2003, The elastic phrase: Modeling the
      dynamics of boundary-adjacent lengthening, Journal of Phonetics 31, 149-180.),
      which would be more difficult to validate with a traditional interval-based
      approach. It is concluded that the FDA time alignment method provides a useful
      tool for characterizing timing patterns in linguistic experimentation based on
      continuous kinematic trajectories.

PMID- 16583911
TI  - Phonological systems in bilinguals: age of learning effects on the stop consonant
      systems of Korean-English bilinguals.
AB  - Interaction of Korean and English stop systems in Korean-English bilinguals as a
      function of age of acquisition (AOA) of English was investigated. It was
      hypothesized that early bilinguals (mean AOA=3.8 years) would more likely be
      native-like in production of English and Korean stops and maintain greater
      independence between Korean and English stop systems than late bilinguals (mean
      AOA=21.4 years). Production of Korean and English stops was analyzed in terms of
      three acoustic-phonetic properties: voice-onset time, amplitude difference
      between the first two harmonics, and fundamental frequency. Late bilinguals were
      different from English monolinguals for English voiceless and voiced stops in all
      three properties. As for Korean stops, late bilinguals were different from Korean
      monolinguals for fortis stops in voice-onset time. Early bilinguals were not
      different from the monolinguals of either language. Considering the independence
      of the two stop systems, late bilinguals seem to have merged English voiceless
      and Korean aspirated stops and produced English voiced stops with similarities to
      both Korean fortis and lenis stops, whereas early bilinguals produced five
      distinct stop types. Thus, the early bilinguals seem to have two independent stop
      systems, whereas the late bilinguals likely have a merged Korean-English system.

PMID- 16583912
TI  - Training the perception of Hindi dental and retroflex stops by native speakers of
      American English and Japanese.
AB  - Perception of second language speech sounds is influenced by one's first
      language. For example, speakers of American English have difficulty perceiving
      dental versus retroflex stop consonants in Hindi although English has both dental
      and retroflex allophones of alveolar stops. Japanese, unlike English, has a
      contrast similar to Hindi, specifically, the Japanese /d/ versus the flapped /r/
      which is sometimes produced as a retroflex. This study compared American and
      Japanese speakers' identification of the Hindi contrast in CV syllable contexts
      where C varied in voicing and aspiration. The study then evaluated the
      participants' increase in identifying the distinction after training with a
      computer-interactive program. Training sessions progressively increased in
      difficulty by decreasing the extent of vowel truncation in stimuli and by adding
      new speakers. Although all participants improved significantly, Japanese
      participants were more accurate than Americans in distinguishing the contrast on
      pretest, during training, and on posttest. Transfer was observed to three new
      consonantal contexts, a new vowel context, and a new speaker's productions. Some
      abstract aspect of the contrast was apparently learned during training. It is
      suggested that allophonic experience with dental and retroflex stops may be
      detrimental to perception of the new contrast.

PMID- 16583913
TI  - Perception of the [m]-[n] distinction in consonant-vowel (CV) and vowel-consonant
      (VC) syllables produced by child and adult talkers.
AB  - The contribution of the nasal murmur and vocalic formant transition to the
      perception of the [m]-[n] distinction by adult listeners was investigated for
      speakers of different ages in both consonant-vowel (CV) and vowel-consonant (VC)
      syllables. Three children in each of the speaker groups 3, 5, and 7 years old,
      and three adult females and three adult males produced CV and VC syllables
      consisting of either [m] or [n] and followed or preceded by [i ae u a],
      respectively. Two productions of each syllable were edited into seven murmur and
      transitions segments. Across speaker groups, a segment including the last 25 ms
      of the murmur and the first 25 ms of the vowel yielded higher perceptual
      identification of place of articulation than any other segment edited from the CV
      syllable. In contrast, the corresponding vowel+murmur segment in the VC syllable
      position improved nasal identification relative to other segment types for only
      the adult talkers. Overall, the CV syllable was perceptually more distinctive
      than the VC syllable, but this distinctiveness interacted with speaker group and
      stimulus duration. As predicted by previous studies and the current results of
      perceptual testing, acoustic analyses of adult syllable productions showed
      systematic differences between labial and alveolar places of articulation, but
      these differences were only marginally observed in the youngest children's
      speech. Also predicted by the current perceptual results, these acoustic
      properties differentiating place of articulation of nasal consonants were
      reliably different for CV syllables compared to VC syllables. A series of
      comparisons of perceptual data across speaker groups, segment types, and syllable
      shape provided strong support, in adult speakers, for the "discontinuity
      hypothesis" [K. N. Stevens, in Phonetic Linguistics: Essays in Honor of Peter
      Ladefoged, edited by V. A. Fromkin (Academic, London, 1985), pp. 243-255],
      according to which spectral discontinuities at acoustic boundaries provide
      critical cues to the perception of place of articulation. In child speakers, the
      perceptual support for the "discontinuity hypothesis" was weaker and the results
      indicative of developmental changes in speech production.

PMID- 16583914
TI  - Extrinsic context affects perceptual normalization of lexical tone.
AB  - The present study explores the use of extrinsic context in perceptual
      normalization for the purpose of identifying lexical tones in Cantonese. In each
      of four experiments, listeners were presented with a target word embedded in a
      semantically neutral sentential context. The target word was produced with a mid
      level tone and it was never modified throughout the study, but on any given trial
      the fundamental frequency of part or all of the context sentence was raised or
      lowered to varying degrees. The effect of perceptual normalization of tone was
      quantified as the proportion of non-mid level responses given in F0-shifted
      contexts. Results showed that listeners' tonal judgments (i) were proportional to
      the degree of frequency shift, (ii) were not affected by non-pitch-related
      differences in talker, (iii) and were affected by the frequency of both the
      preceding and following context, although (iv) following context affected tonal
      decisions more strongly than did preceding context. These findings suggest that
      perceptual normalization of lexical tone may involve a "moving window" or
      "running average" type of mechanism, that selectively weights more recent pitch
      information over older information, but does not depend on the perception of a
      single voice.

PMID- 16583915
TI  - The relative roles of vowels and consonants in discriminating talker identity
      versus word meaning.
AB  - Three experiments tested the hypothesis that vowels play a disproportionate role
      in hearing talker identity, while consonants are more important in perceiving
      word meaning. In each study, listeners heard 128 stimuli consisting of two
      different words. Stimuli were balanced for same/different meaning, same/different
      talker, and male/female talker. The first word in each was intact, while the
      second was either intact (Experiment 1), or had vowels ("Consonants-Only") or
      consonants wels-Only") replaced by silence (Experiments 2, 3). Different
      listeners performed a same/ different judgment of either talker identity (Talker)
      or word meaning (Meaning). Baseline testing in Experiment 1 showed above-chance
      performance in both, with greater accuracy for Meaning. In Experiment 2, Talker
      identity was more accurately judged from Vowels-Only stimuli, with modestly
      better overall Meaning performance with Consonants-Only stimuli. However,
      performance with vowel-initial Vowels-Only stimuli in particular was most
      accurate of all. Editing Vowels-Only stimuli further in Experiment 3 had no
      effect on Talker discrimination, while dramatically reducing accuracy in the
      Meaning condition, including both vowel-initial and consonant-initial Vowels-Only
      stimuli. Overall, results confirmed a priori predictions, but are largely
      inconsistent with recent tests of vowels and consonants in sentence
      comprehension. These discrepancies and possible implications for the evolutionary
      origins of speech are discussed.

PMID- 16583916
TI  - The use of visual cues in the perception of non-native consonant contrasts.
AB  - This study assessed the extent to which second-language learners are sensitive to
      phonetic information contained in visual cues when identifying a non-native
      phonemic contrast. In experiment 1, Spanish and Japanese learners of English were
      tested on their perception of a labial/ labiodental consonant contrast in audio
      (A), visual (V), and audio-visual (AV) modalities. Spanish students showed better
      performance overall, and much greater sensitivity to visual cues than Japanese
      students. Both learner groups achieved higher scores in the AV than in the A test
      condition, thus showing evidence of audio-visual benefit. Experiment 2 examined
      the perception of the less visually-salient /1/-/r/ contrast in Japanese and
      Korean learners of English. Korean learners obtained much higher scores in
      auditory and audio-visual conditions than in the visual condition, while Japanese
      learners generally performed poorly in both modalities. Neither group showed
      evidence of audio-visual benefit. These results show the impact of the language
      background of the learner and visual salience of the contrast on the use of
      visual cues for a non-native contrast. Significant correlations between scores in
      the auditory and visual conditions suggest that increasing auditory proficiency
      in identifying a non-native contrast is linked with an increasing proficiency in
      using visual cues to the contrast.

PMID- 16583917
TI  - The effects of hearing loss on the contribution of high- and low-frequency speech
      information to speech understanding. II. Sloping hearing loss.
AB  - The speech understanding of persons with sloping high-frequency (HF) hearing
      impairment (HI) was compared to normal hearing (NH) controls and previous
      research on persons with "flat" losses [Hornsby and Ricketts (2003). J. Acoust.
      Soc. Am. 113, 1706-1717] to examine how hearing loss configuration affects the
      contribution of speech information in various frequency regions. Speech
      understanding was assessed at multiple low- and high-pass filter cutoff
      frequencies. Crossover frequencies, defined as the cutoff frequencies at which
      low- and high-pass filtering yielded equivalent performance, were significantly
      lower for the sloping HI, compared to NH, group suggesting that HF HI limits the
      utility of HF speech information. Speech intelligibility index calculations
      suggest this limited utility was not due simply to reduced audibility but also to
      the negative effects of high presentation levels and a poorer-than-normal use of
      speech information in the frequency region with the greatest hearing loss (the HF
      regions). This deficit was comparable, however, to that seen in low-frequency
      regions of persons with similar HF thresholds and "flat" hearing losses
      suggesting that sensorineural HI results in a "uniform," rather than frequency
      specific, deficit in speech understanding, at least for persons with HF
      thresholds up to 60-80 dB HL.

PMID- 16583918
TI  - Constrained tone transformation technique for separation and combination of
      Mandarin tone and intonation.
AB  - This paper addresses a classical but important problem: The coupling of lexical
      tones and sentence intonation in tonal languages, such as Chinese, focusing
      particularly on voice fundamental frequency (F1) contours of speech. It is
      important because it forms the basis of speech synthesis technology and prosody
      analysis. We provide a solution to the problem with a constrained tone
      transformation technique based on structural modeling of the F1 contours. This
      consists of transforming target values in pairs from norms to variants. These
      targets are intended to sparsely specify the prosodic contributions to the F1
      contours, while the alignment of target pairs between norms and variants is based
      on underlying lexical tone structures. When the norms take the citation forms of
      lexical tones, the technique makes it possible to separate sentence intonation
      from observed F0 contours. When the norms take normative F0 contours, it is
      possible to measure intonation variations from the norms to the variants, both
      having identical lexical tone structures. This paper explains the underlying
      scientific and linguistic principles and presents an algorithm that was
      implemented on computers. The method's capability of separating and combining
      tone and intonation is evaluated through analysis and re-synthesis of several
      hundred observed F0 contours.

PMID- 16583919
TI  - Interferometric studies of a piano soundboard.
AB  - Electronic speckle pattern interferometry has been used to study the deflection
      shapes of a piano soundboard. A design for an interferometer that can image such
      an unstable object is introduced, and interferograms of a piano soundboard
      obtained using this interferometer are presented. Deflection shapes are analyzed
      and compared to a finite-element model, and it is shown that the force the
      strings exert on the soundboard is important in determining the mode shapes and
      resonant frequencies. Measurements of resonance frequencies and driving-point
      impedance made using the interferometer are also presented.

PMID- 16583920
TI  - Contribution to harmonic balance calculations of self-sustained periodic
      oscillations with focus on single-reed instruments.
AB  - The harmonic balance method (HBM) was originally developed for finding periodic
      solutions of electronical and mechanical systems under a periodic force, but has
      been adapted to self-sustained musical instruments. Unlike time-domain methods,
      this frequency-domain method does not capture transients and so is not adapted
      for sound synthesis. However, its independence of time makes it very useful for
      studying any periodic solution, whether stable or unstable, without care of
      particular initial conditions in time. A computer program for solving general
      problems involving nonlinearly coupled exciter and resonator, HARMBAL, has been
      developed based on the HBM. The method as well as convergence improvements and
      continuation facilities are thoroughly presented and discussed in the present
      paper. Applications of the method are demonstrated, especially on problems with
      severe difficulties of convergence: the Helmholtz motion (square signals) of
      single-reed instruments when no losses are taken into account, the reed being
      modeled as a simple spring.

PMID- 16583921
TI  - Spectral characteristics of three styles of Croatian folk singing.
AB  - This paper examines the differences between three Croatian folk singing styles,
      namely klapa, ojkanje, and tarankanje. In order to factor out singer-specific
      properties, each of the styles was performed by the same 12 professional male
      singers. The 36 performances were analyzed with a long-term average spectrum
      (LTAS) method from which direct effects of the pitch distribution were removed.
      After factoring out each singer's average, the 36 pitch-corrected LTAS contours
      were reduced to a two-dimensional representation in two ways: (1) a principal
      component analysis and (2) a graphical plot of spectral slope versus speaker's
      formant strength. Both ways clearly separate the three styles. The spectrum of
      the klapa style turns out to be similar to that of speech. The ojkanje style is
      extremely loud and shows two spectral peaks: a sharp one tuned at twice the
      fundamental frequency and appropriate for long-distance communication on mountain
      slopes, and a broad one around 3.5 kHz, reminiscent of a speaker's formant. The
      tarankanje style has a very flat spectrum implemented by vocal pressedness and
      nasality, which is appropriate for blending into or imitating the timbral
      characteristics of the sopile folk instrument.

PMID- 16583922
TI  - Acoustic detection and classification of Microchiroptera using machine learning:
      lessons learned from automatic speech recognition.
AB  - Current automatic acoustic detection and classification of microchiroptera
      utilize global features of individual calls (i.e., duration, bandwidth, frequency
      extrema), an approach that stems from expert knowledge of call sonograms. This
      approach parallels the acoustic phonetic paradigm of human automatic speech
      recognition (ASR), which relied on expert knowledge to account for variations in
      canonical linguistic units. ASR research eventually shifted from acoustic
      phonetics to machine learning, primarily because of the superior ability of
      machine learning to account for signal variation. To compare machine learning
      with conventional methods of detection and classification, nearly 3000 search
      phase calls were hand labeled from recordings of five species: Pipistrellus
      bodenheimeri, Molossus molossus, Lasiurus borealis, L. cinereus semotus, and
      Tadarida brasiliensis. The hand labels were used to train two machine learning
      models: a Gaussian mixture model (GMM) for detection and classification and a
      hidden Markov model (HMM) for classification. The GMM detector produced 4% error
      compared to 32% error for a baseline broadband energy detector, while the GMM and
      HMM classifiers produced errors of 0.6 +/- 0.2% compared to 16.9 +/- 1.1% error
      for a baseline discriminant function analysis classifier. The experiments showed
      that machine learning algorithms produced errors an order of magnitude smaller
      than those for conventional methods.

PMID- 16583924
TI  - Information entropy of humpback whale songs.
AB  - The structure of humpback whale (Megaptera novaeangliae) songs was examined using
      information theory techniques. The song is an ordered sequence of individual
      sound elements separated by gaps of silence. Song samples were converted into
      sequences of discrete symbols by both human and automated classifiers. This paper
      analyzes the song structure in these symbol sequences using information entropy
      estimators and autocorrelation estimators. Both parametric and nonparametric
      entropy estimators are applied to the symbol sequences representing the songs.
      The results provide quantitative evidence consistent with the hierarchical
      structure proposed for these songs by Payne and McVay [Science 173, 587-597
      (1971)]. Specifically, this analysis demonstrates that: (1) There is a strong
      structural constraint, or syntax, in the generation of the songs, and (2) the
      structural constraints exhibit periodicities with periods of 6-8 and 180-400
      units. This implies that no empirical Markov model is capable of representing the
      songs' structure. The results are robust to the choice of either human or
      automated song-to-symbol classifiers. In addition, the entropy estimates indicate
      that the maximum amount of information that could be communicated by the sequence
      of sounds made is less than 1 bit per second.

PMID- 16583923
TI  - Effects of nonlinear propagation, cavitation, and boiling in lesion formation by
      high intensity focused ultrasound in a gel phantom.
AB  - The importance of nonlinear acoustic wave propagation and ultrasound-induced
      cavitation in the acceleration of thermal lesion production by high intensity
      focused ultrasound was investigated experimentally and theoretically in a
      transparent protein-containing gel. A numerical model that accounted for
      nonlinear acoustic propagation was used to simulate experimental conditions.
      Various exposure regimes with equal total ultrasound energy but variable peak
      acoustic pressure were studied for single lesions and lesion stripes obtained by
      moving the transducer. Static overpressure was applied to suppress cavitation.
      Strong enhancement of lesion production was observed for high amplitude waves and
      was supported by modeling. Through overpressure experiments it was shown that
      both nonlinear propagation and cavitation mechanisms participate in accelerating
      lesion inception and growth. Using B-mode ultrasound, cavitation was observed at
      normal ambient pressure as weakly enhanced echogenicity in the focal region, but
      was not detected with overpressure. Formation of tadpole-shaped lesions, shifted
      toward the transducer, was always observed to be due to boiling. Boiling bubbles
      were visible in the gel and were evident as strongly echogenic regions in B-mode
      images. These experiments indicate that nonlinear propagation and cavitation
      accelerate heating, but no lesion displacement or distortion was observed in the
      absence of boiling.

PMID- 16583925
TI  - Acoustic features of objects matched by an echolocating bottlenose dolphin.
AB  - The focus of this study was to investigate how dolphins use acoustic features in
      returning echolocation signals to discriminate among objects. An echolocating
      dolphin performed a match-to-sample task with objects that varied in size, shape,
      material, and texture. After the task was completed, the features of the object
      echoes were measured (e.g., target strength, peak frequency). The dolphin's error
      patterns were examined in conjunction with the between-object variation in
      acoustic features to identify the acoustic features that the dolphin used to
      discriminate among the objects. The present study explored two hypotheses
      regarding the way dolphins use acoustic information in echoes: (1) use of a
      single feature, or (2) use of a linear combination of multiple features. The
      results suggested that dolphins do not use a single feature across all object
      sets or a linear combination of six echo features. Five features appeared to be
      important to the dolphin on four or more sets: the echo spectrum shape, the
      pattern of changes in target strength and number of highlights as a function of
      object orientation, and peak and center frequency. These data suggest that
      dolphins use multiple features and integrate information across echoes from a
      range of object orientations.

PMID- 16583926
TI  - Elastic stiffness coefficients (c11, C33, and C13) for freshly excised and
      formalin-fixed myocardium from ultrasonic velocity measurements.
AB  - The goal of this study was to measure elastic stiffness coefficients of freshly
      excised and subsequently formalin-fixed myocardial tissue. Our approach was to
      measure the angle-dependent phase velocities associated with the propagation of a
      longitudinal ultrasonic wave (3-8 MHz) in ovine myocardium using phase
      spectroscopy techniques and to interpret the results in the context of
      orthotropic and transversely isotropic models describing the elastic properties
      of myocardium. The phase velocity results together with density measurements were
      used to obtain the elastic stiffness coefficients c11, c33, and c13 for both
      symmetries. The results for the elastic stiffness coefficients c11, c33, and c13
      are the same for both symmetries. Measurements for freshly excised myocardium and
      the same tissue after a period of formalin fixation were compared to examine the
      impact of fixation on the elastic stiffness coefficients.

PMID- 16583929
TI  - Classification of vocalizations of killer whales using dynamic time warping.
AB  - A large number of killer whale sounds have recently been classified perceptually
      into Call Types. [A. Hodgins-Davis, thesis, Wellesley College (2004)]. The
      repetition rate of the pulsed component of five or more examples of each call
      type has been calculated using a modified form of the FFT based comb-filter
      method. A dissimilarity or distance matrix for these sounds was calculated using
      dynamic time warping to compare their melodic contours. These distances were
      transformed into a component space using multidimensional scaling and the
      resulting points were clustered with a kmeans algorithm. In grouping 57 sounds
      into 9 call types, a single discrepancy between the perceptual and the automated
      methods occurred.

PMID- 16583930
TI  - Auditory brainstem response in a harbor porpoise show lack of automatic gain
      control for simulated echoes.
AB  - The auditory brainstem response (ABR) response to simulated echolocation clicks
      was studied in a harbor porpoise, Phocoena phocoena, to determine the
      relationship between the animal's perceived echo strength and the simulated
      target distance. In one experiment the click level at the listening post was kept
      constant while delay was changed, in another, the level was varied to approximate
      spreading losses. Results of both experiments indicate that there is no automatic
      gain control in the hearing system of this harbor porpoise.

PMID- 16583932
TI  - [A randomized, double-blind, placebo-controlled study of the antilipemic efficacy
      and tolerability of food supplement policosanol in patients with moderate
      hypercholesterolemia].
AB  - This randomized, double-blind, placebo-controlled crossover study was performed
      in 67 patients of both sexes aged 20 to 78 years with moderate
      hypercholesterolemia to investigate the antilipemic efficacy and tolerability of
      food supplement policosanol--a mixture of aliphatic primary alcohols from rice
      (Oryza sp.). After a 8-week run-in period in which patients were placed on
      therapeutic lifestyle changes, in particular cholesterol-lowering diet, they were
      randomly assigned to receive policosanol 10 mg capsules or placebo capsules once
      daily with the evening meal for 8 weeks. During next 8 weeks those receiving
      policosanol during the first 8 weeks, received placebo and those taking placebo
      during the first 8 weeks, received policosanol. Total cholesterol (C), LDL-C, HDL
      C, HDL2-C, HDL3-C, triglycerides, oxidized LDL, apoproteins A I and B and
      lipoprotein (a) as well as AST, ALT, GGT, CK, blood glucose and bilirubin were
      determined before the treatment, after the first part of the study i.e. after the
      first 8 weeks and at the end of the study, i.e after the second 8 weeks.
      Policosanol significantly reduced plasma total cholesterol and increased
      apoprotein A I but did not change plasma triglycerides, HDL-C, HDL2-C, HDL3-C,
      LDL-C, oxidized LDL, Lp (a) and apoproteinS. It was well tolerated, with no drug
      related effects on safety parameters such as serum aminotransferases, blood
      glucose, bilirubin, and CK, neither did it cause any clinical adverse reactions.

PMID- 16583933
TI  - [Transluminal balloon valvuloplasty in neonates and infants with critical aortic
      stenosis].
AB  - The purpose of this study was to evaluate children who underwent balloon
      valvuloplasty due to critical aortic stenosis following clinical (low cardiac
      output, cardiogenic shock, congestive heart failure) and echocardiographic
      criteria (morphological evidence of left ventricular hypertrophy, with depression
      of left ventricular function, irrespective of transvalvular gradient). We
      assessed the effectiveness of balloon valvuloplasty in 5 children (all male) who
      were submitted to aortic valve balloon dilatation over 3.5 years (10.1998
      05.2003). The age at dilatation was 29+/-24 days, BW 3.92+/-0.82 kg and BSA
      0.24+/-0.03 m2. In all children the balloon valvuloplasty was performed with
      manual inflation of balloon at 4-6 bars through the femoral artery. The mean
      systolic pressure gradient across the aortic valve decreased from 68+/-20.5 mmHg
      to 9+/-10.95 mmHg, i.e. by 85%, (p<0.01). Aortic valve ring diameter was 9.2+0.84
      mm, and balloon/aortic ring ratio 0.8-0.04. The degree of aortic insufficiency
      immediately after the dilatation did not significantly increase. Dilatation was
      performed without complications. Long term results were evaluated in all patients
      3.2 - 54 months after valvuloplasty and revealed the continuously increasing
      residual aortic valve gradient (Doppler measurement) 33+/-10.95 mmHg to be
      significantly lower (p<0.01) than before valvuloplasty. None of the children was
      showing clinical symptoms of the disease. According to echocardiographic analysis
      two of them developed aortic valvar insufficiency grade II, two had trivial
      insufficiency, one was without insufficiency. One child is an candidate for the
      Ross procedure in future (gradient 50 mmHg, insufficiency grade II, age 4.5
      years.). Balloon valvuloplasty provides effective interventional method in the
      treatment of the neonates and infants with critical aortic stenosis.

PMID- 16583934
TI  - [Doxycycline induced esophageal ulcers: report of two cases and review of the
      literature].
AB  - Doxycycline-induced esophageal ulcers (DIEU) are rarely observed in endoscopy
      units. On the other hand doxycycline itself has been claimed as an offending drug
      in 1/4 out of about 1000 cases of drug induced esophageal ulcers reported in the
      literature so far. In this article we present two patients with typical history
      and endoscopic features of esophageal ulcers as an consequence of doxycycline
      therapy. The therapy consisted of doxycycline withdrawal along with treatment
      with proton pump inhibitors and sucralfate which had led to disappearance of
      chest discomfort within one week period. Fourteen days of the tratment beginning
      complete recovery of the mucosal defects has occurred in both patients. In
      conclusion, in case of chest pain and painful swallowing occurring in a person
      who takes doxycycline, DIEU has to be considered followed by the esophagoscopy
      which would confirm clinical suspicious with high specificity leading to correct
      diagnosis and treatment of this condition.

PMID- 16583935
TI  - [Hypophosphatasia: report of two affected girls with spontaneous improvement of
      skeletal defects].
AB  - Hypophosphatasia is a rare metabolic bone disease characterised by defective bone
      and teeth mineralisation owing to reduced activity of tissue nonspecific alkaline
      phosphatase due to mutation in ALPL (TNSALP) gene. Seven clinical forms of HP
      have been described. The severity and the clinical course of hypophosphatasia are
      highly variable, ranging from intrauterine death to premature loss of teeth only.
      We report on two affected girls with hypophosphatasia and spontaneous improvement
      of skeletal defects. The first patient is a four-year-old girl with perinatal
      nonlethal form of the disease. From another family is the 15 year-old-girl, with
      typical clinical and radiological features of childhood hypophosphatasia. The
      diagnosis was based on clinical course, radiological findings, low serum alkaline
      phosphatase activity in patients and their parents, and later confirmed by the
      molecular analysis of the ALPL gene. We have described in more detail the
      clinical manifestations and radiological findings relevant for the recognition of
      hypophosphatasia, because the disorder is rare, clinical presentation
      heterogeneous and the recognition rate poor.

PMID- 16583936
TI  - [Anesthesia and perioperative management of patients with resection for
      esophageal carcinoma].
AB  - The current approach to the anesthetic procedure and postoperative intensive
      therapy after esophageal resection for esophageal carcinoma, as well as
      characteristic perioperative pathophysiological events are presented. The
      contributory factors of severe postsurgical morbidity are considered too.
      Esophagectomy is an extented procedure which includes laparotomy, thoracotomy and
      often cervicotomy, and carries a great surgical stress with a huge fluid shift.
      It is mostly performed in the aged population with a certain co-morbidity:
      malnutrition, compromized immune status, respiratory and cardiovascular diseases.
      Standardization of esophageal resection and reconstructive techniques together
      with the optimal perioperative management significantly reduce operative
      mortality. Preoperatively, the patients' nutritive, respiratory and cardiac
      status should be improved. Intraoperatively, beside adequate depth of anesthesia
      which enables the optimal metabolic response to surgical stress, the invasive
      hemodynamic monitoring with insertion of pulmonary artery catheter is of great
      importance. The aim is to ensure adequate tissue perfusion and oxygenation
      avoiding pulmonary overhydration at the same time. Postoperatively, important
      role has epidural analgesia, allowing proper breathing and coughing and routine
      usage of fiberbronchoscopy for clearance of pulmonary secretion. After resection
      there are several conditions which contribute to cough and swallow disturbances:
      bilateral vagotomy, the absence of upper and lower esophageal sphincters,
      transient aperistalsis of the substitute, sometimes a transient vocal cord
      paresis. All of these make patients prone to regurgitation and aspiration of
      duodenal and gastric juice. Currently, the pulmonary complications are the
      leading problems after this procedure, so their prevention and early treatment
      are the key tasks for the clinicians.

PMID- 16583937
TI  - [Laparoscopic colorectal surgery].
AB  - Laparoscopy is not a standard approach for colorectal diseases yet. This is due
      to the technically demanding procedure, the necessary equipment and open
      questions on cancer surgery. In this paper, short-term results in a small group
      of patients together with a review of the recent publications are presented. Six
      patients were operated between April 2002 and October 2003, without
      intraoperative complications or conversions. The average operation time was 120
      minutes, and the average hospital stay was seven days. Patients with colorectal
      carcinoma were operated with curative intent. Recent publications are presenting
      new information on laparoscopy and colorectal cancer. For an adequate
      laparoscopic colorectal resection, experience in laparoscopy together with proper
      education is mandatory.

PMID- 16583938
TI  - [Neurofibromatosis type 1 (von Recklinghausen's disease or peripheral
      neurofibromatosis): from phenotype to gene].
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with a prevalence
      of about 1/3000. The clinical diagnosis of NF1 is based on the presence of two or
      more of the following criteria: six or more cafe au lait spots, >2 neurofibromas
      of any type or 1 plexiform neurofibroma, freckling in the axillary or inguinal
      region, optic glioma, a distinctive osseous lesion such as sphenoid dysplasia or
      thinning of long bone cortex with or without pseudoarthrosis, and a first degree
      relative with NF1. The disease has numerous complications. The pathogenesis is
      not clarified. The NF1 gene is a megagene (length of app. 350 kilobases of
      genomic DNA), localised on the long arm of the 17th chromosome at the position
      17q11.2. The mutation rate for NF1-gene is high. The half of all cases of NF1 are
      from new mutations. The gene protein product - neurofibromin plays an important
      role in the tumorogenesis as a tumor-suppressor gene. Molecular genetic
      evaluation for the identification of disease-causing mutations is possible in cca
      20% patients. The patient care is best done in specialised neurofibromatosis
      centers.

PMID- 16583939
TI  - [Current concept of diagnostic procedure in Alzheimer's disease: an evidence
      based approach].
AB  - The aim of this article is to provide evidence-based recommendations for early
      diagnosis of Alzheimer's disease (AD) and hereby to give clinician the guidelines
      for optimal detection of patients with AD. Our intention is also to unify
      diagnostic schemes in accordance with our objective and specific possibilities.
      Basic diagnostic procedures primaruly are anamnesis and clinical examination with
      rational usage of neuroimaging, electrophysiological and laboratory procedures.
      Using these guidelines in medical practice in Croatia would be a solid basis for
      future epidemiological and clinical multicenter studies.

PMID- 16583940
TI  - [Medical therapy of benign prostatic hyperplasia].
AB  - The aim of treatment for benign prostatic hyperplasia is relieving lower urinary
      tract symptoms, desreasing bladder outlet obstruction, improving bladder
      emptying, ameliorating detrusor instability, reversing renal insufficiency, and
      preventing future episodes of gross hematuria, urinary tract infection and
      urinary retention. A potent role of medical therapy is to prevent the development
      and/or progression of benign prostatic hyperplasia. Medical therapies
      investigated for benign prostatic hyperplasia include plant extracts, alpha
      adrenergic blockers and 5-alpha-reductase inhibitors. Clinical observations
      suggest that the efficacy of combination therapy could be superior to that of
      individual monotherapies.

PMID- 16583941
TI  - [Medical examination prior to trade school admission].
AB  - Regulation on medical examination prior to apprenticeship is built in the Act on
      Trades and Crafts. Medical examinations of the students before admission to
      secondary craft schools have been done regularly since 1993. Between 11,000 and
      14,000 students are admitted to secondary craft schools in the Republic of
      Croatia annually. According to statistics, about 10% of students have obvious
      health problems, about 5% of students have healt problems which vitally limit
      their capacity in particular crafts. This statistic refers to about 3% of the
      examined students. Medical examinations of students prior to admission to craft
      schools represent a particular sort of health capacity examinations. The paper
      includes applications for the most freqent trades and crafts, and findings of the
      craft school admission examinations.

PMID- 16583942
TI  - [Report on an emotional disorder with separation anxiety in a five year old boy].

PMID- 16583943
TI  - [Comparison of blood glucose levels measured in laboratory and by glucometer].

PMID- 16583944
TI  - [Guidelines for antimicrobial treatment and prophylaxis of urinary tract
      infections].

PMID- 16583945
TI  - [The evaluation of cardiovascular risk factors in renal transplantation
      candidates].

PMID- 16583946
TI  - [The cardiac lung].
AB  - Since lungs, great vessels and heart share together the main volume of the
      thorax, itself limited by the thoracic wall, variations in pressure or volume of
      each one must influence the work of the others especially in case of disease.
      Failure of the left heart overloads the pulmonary vascular bed, induces an
      interstitial oedema followed by an alveolar oedema with mostly restrictive
      functional consequences on the lung and disturbed gas exchange. Heart failure can
      be due to systolic or diastolic dysfunction. These consequences of myocardial and
      valve diseases of the left heart are initially revealed by unusual dyspnea during
      exercise worsening progressively to symptoms at rest and even during sleep.
      Informations obtained from history, physical examination, biology, radiography
      and echocardiography imaging procedures, respiratory function tests and
      polysomnography help to precise the diagnosis and the prognosis. The treatment of
      this cardiac lung conditions depends on its precise etiology.

PMID- 16583947
TI  - [Hypertrophic pulmonary osteoarthropathy].

PMID- 16583948
TI  - [Eczemas: treating them more effectively to limit their psychological and social
      impact].

PMID- 16583949
TI  - [Epidemiology and pathophysiology of eczemas].
AB  - Pathophysiological characteristics of these two types of eczema, both involve
      antigen specific effector T lymphocytes and down-regulatory CD4+ T cells (Treg).
      These cells are responsible for the cutaneous inflammatory response through the
      production of inflammatory cytokines and the destruction of keratinocytes by
      apoptosis. The main difference between these two types of disease is the nature
      of the environmental antigen. Indeed, protein allergens are involved in cases of
      atopic dermatitis whereas non protein chemicals (calles haptens) are responsible
      for allergic contact dermatitis. The skin lesions of eczema follow the activation
      of antigen specific T lymphocytes within the skin, leading to the production of
      inflammatory cytokines and to the destruction of keratinocytes by apoptosis. CD4+
      Treg cells are endowed with down-regulatory and tolerogenic functions since they
      limit the skin inflammation in patients and prevent sensitization and induction
      of eczema in normal individuals. Eczema should therefore be considered as
      inflammatory dermatoses caused by the loss of immune tolerance to environmental
      antigens. Different strategies capable of restoring immune tolerance could avoid
      eczema outbursts and/or induce prolonged remissions of the disease.

PMID- 16583950
TI  - [Atopic dermatitis in children].
AB  - Atopic dermatitis is a chronic inflammatory and recurrent dermatosis, the
      frequency of which increases regularly in industrialised countries. It begins in
      the first months of life and the clinical presentation changes with the age of
      the child. The diagnostic is clinical in the majority of cases. Sometimes
      allergological explorations are necessary. The treatment has two objectives:
      treatment of the flares (mainly topical corticosteroids) and preventive adjuvant
      measures. The use of topical immunosuppressors reinforces the therapeutic
      management, after failure of topical corticosteroids.

PMID- 16583951
TI  - [Atopic dermatitis in adults].
AB  - Eczema atopic is rare in adult. It is either a relapse caused by a modification
      of the environment (stress, cutaneous irritation, contact allergy), or the
      persistence since the early childhood of an atopic eczema usually severe and
      worsened by the use of a discontinuous topical steroids. The therapeutic
      effectiveness is based on the 'patient based medicine' approach, on the daily use
      of gradually diluted topical steroids, on the judicious use of topical
      immunosuppressive drugs like Protopic, and sometimes on the temporary or
      prolonged use of systemic drugs like ciclosporine, methotrexate, or mycophenolate
      mofetil.

PMID- 16583952
TI  - [Atopic dermatitis school: therapeutic education of atopic patients].
AB  - The difficulties encountered in treating refractory atopic dermatitis may be
      secondary to the severity of the disease, to poor compliance or to the extent of
      the psychological impact. Therapeutic education of the patient, as performed in
      the atopic dermatitis school, represents a major breakthrough in the care of such
      patients.

PMID- 16583953
TI  - [Diagnosis and treatment strategies in case of suspicion of contact dermatitis].
AB  - Contact dermatitis may be either irritant, allergic or both. The differential
      diagnosis is based on information from the patient, nature and concentration of
      chemicals involved and clinical examination. In case of suspicion of allergic
      contact dermatitis, the search for the responsible allergen(s) is built on patch
      testing. Positive patch test results, the current and/or past relevance of which
      has to be assessed, are confirmative. Additional tests, such as the repeated open
      application test, are sometimes recommended. Treatment which is symptomatic, is
      mainly based upon corticosteroids, either local or systemic; efficacy is rather
      limited. By any means, it cannot be substituted to the eviction of allergens.
      Primary and secondary prevention are linked with the complete eviction of
      allergens, but this caveat can be attenuated in some circumstances.

PMID- 16583954
TI  - [Allergies to cosmetics].
AB  - The protean clinical delayed hypersensitivity reactions or the less common
      immediate hypersensitivity reactions can raise major diagnostic challenges,
      particularly as sensitisation can occur directly, indirectly or from a distance,
      with the allergen being handborne, airborne, or transmitted vicariously.
      Identification of the offending allergen among the vast array of potential
      candidates requires an exhaustive evaluation. The most common offenders are
      fragrances, which are ubiquitous, being found in a host of known or occult
      sources preservatives, hair dyes, excipient component, formaldehyde resins, and
      acrylic resins.

PMID- 16583955
TI  - [Latex allergy].
AB  - Immediate hypersensitivity to natural rubber latex has increased since the early
      1980s. High prevalence of latex sensitization and allergy are observed among
      healthcare workers, atopic individuals and children who had undergone multiple
      surgical operations (spina bifida, congenital anomalies). Presenting symptoms are
      polymorphous: contact urticaria, rhinitis, conjunctivitis, asthma, and
      anaphylaxis. Corn-starch-latex particles released in the air after powdered
      gloves manipulation may be inhaled and lead to occupational asthma. The diagnosis
      may be made by a focused clinical history, prick-test, detection of specific IgE
      antibody and challenge test. Almost half of patients allergic to natural rubber
      latex show an associated fruit allergy: avocado, banana, kiwi, chestnut. Most of
      cutaneous delayed reactions (eczema) to rubber are caused by rubber additives
      (accelerators of vulcanization, anti-oxidants).

PMID- 16583956
TI  - [Medical studies: fifty years for reforms].

PMID- 16583957
TI  - [Acute lymphoblastic leukaemia. Acute myeloblastic leukaemia].

PMID- 16583958
TI  - [Chronic respiratory failure].

PMID- 16583959
TI  - [Feeding and nutritional requirements of infants and children].

PMID- 16583960
TI  - [Evaluation and care of a full-term newborn].

PMID- 16583961
TI  - [Limping and gait disorders in the child].

PMID- 16583962
TI  - [The plateau d'Assy sanatorium complex].

PMID- 16583963
TI  - Study on physical and some serum parameters of inhabitants living in agricultural
      Terai region, Nepal.
AB  - Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma
      glutamyltranspeptidase (gamma-GTP), lactate dehydrogenase (LDH), urea nitrogen
      (BUN), uric acid (UA) and creatinine (CRE) levels were examined in 183 people (98
      males and 85 females aged 10 to 68 years) living in Terai region in Nepal. The
      mean values of serum components examined did not differ by sex in the age group
      of 10-14 years. The mean values of serum AST, ALT and gamma-GTP levels differed
      significantly between the sexes (P<0.01). The all physical measurements and serum
      parameters observed correlated well in males, but a few of them correlated in
      females. The AST-ALT, AST-gamma-GTP, ALT-CRE and BUN-CRE correlated well in both
      sexes. The UA correlated with ALT and gamma-GTP, CRE with gamma-GTP, LDH and UA
      in males, while only AST-LDH and gamma-GTP-BUN correlated in females. The levels
      of most of the serum components examined in this study were within normal ranges
      for Japanese and others. However, it seemed to be necessary to improve their
      living conditions as these serum components are related to hepatic or renal
      function and the infectious diseases.

PMID- 16583964
TI  - The observation of response to cardiovascular system at periextubation period
      after continuous epidural anesthesia combined with general anesthesia.
AB  - The observation of cardiovascular response at peri-extubation period after
      continuous epidural anesthesia combined with mild general anesthesia was studied.
      Fifty patients of carcinoma esophagus were randomly divided into two groups,
      general anesthesia + epidural anesthesia combined group and control group (only
      general anesthesia), each 25 cases in one group, using a multifunctional monitor,
      continuous monitoring and recording was done for ECG, systolic pressure (SP),
      diastolic pressure (DP), heart rate (HR), oxygen saturation (Spo2) and rhythm of
      heart during the peri-extubation period. Severe cardiovascular instability was
      detected in control group during peri-extubation period, especially at the time
      of extubation, even higher than the baseline values (p<0.05). In combined group,
      the cardiovascular instability was far less, only a slight increase was noted at
      the time of extubation (p>0.05). The use of halothane was far less in combined
      group than that in control group (p<0.05). Mild general anesthesia combined with
      continuous epidural anesthesia is a good modality of anesthesia that can
      obviously decreased cardiovascular instability during peri-extubation.

PMID- 16583965
TI  - Sedation with ketamine: a safe and effective anaesthetic agent for children in
      the developing world.
AB  - Recently there has been a resurgence in the utilization of ketamine, a unique
      anaesthetic, for emergency procedures requiring sedation. The purpose of the
      present study was to examine the safety and efficacy of ketamine for sedation in
      the treatment of children's fractures in the small clinic setup of rural Nepal.
      One hundred and fourteen children (average age, 5.3 years; range, twelve months
      to ten years and ten months) who underwent closed reduction of an isolated
      fracture or dislocation in the Orthopaedic & Trauma Clinic at Janakpurdham were
      prospectively evaluated. Ketamine hydrochloride was administered intravenously
      (at a dose of less than two milligrams per kilogram of body weight) in ninety
      nine of the patients and intramuscularly (at a dose of four milligrams per
      kilogram of body weight) in the other fifteen. Adequate fracture reduction was
      obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty
      nine parents present during the reduction were pleased with the sedation and
      would allow it to be used again in a similar situation. Minor side effects
      included nausea (thirteen patients), emesis (eight of the thirteen patients with
      nausea), clumsiness (evident as ataxic movements in ten patients), and dysphonic
      reaction (one patient). No long-term sequelae were noted, and no patients had
      hallucinations or nightmares. Ketamine reliably, safely, and quickly provided
      adequate sedation to effectively facilitate the reduction of children's fractures
      at our institution. Therefore, it was ideal for small clinic in our setup.

PMID- 16583966
TI  - Growth retardation and lethality induced by adriblastina in chick embryo.
AB  - The low (1.2 mg/kg) and high (2.4 mg/kg) therapeutic dose of adriblastina,
      dissolved in 0.04 ml of distilled water was injected into the chick embryo at
      different duration of the incubation. The control chick embryo received equal
      volume of distilled water at the same duration. All groups of embryo were
      collected on day 19 of gestation. The treated embryo showed growth retardation
      and lethality in a dose dependence response. The lethality and growth retardation
      in both treated groups were found significantly different (p<0.001) as compared
      with the control chick embryo. Similarly the groups treated on different days
      showed a time sequential effect on the developing chick embryo. Our observation
      had revealed that the drug is teratogenic to the chick embryo.

PMID- 16583967
TI  - Measles outbreak in a vaccinated population in Dhankutta.
AB  - A measles outbreak occurred in Dhankutta town in year 2056 Falgun to 2057 Baishak
      (3 months). A total of 130 cases were registered at the Dhankutta District
      Hospital. A large proportion of the cases had severe disease with complications
      and were admitted at the hospital. None of the patients registered at the
      hospital died. Interestingly, 50.0% of cases were in higher age group (10 years
      and above) which is an unusual trend in developing countries. All the cases gave
      history of measles vaccination, which points towards the need for investigation
      of vaccine efficacy and cold chain efficiency.

PMID- 16583968
TI  - Voluntary surgical contraception: a study on level of satisfaction.
AB  - Voluntary surgical contraception (VSC) is said to be one of the most popular,
      safe, effective and long term methods of birth control not only in Nepal but also
      in the world One of the very frequently suspected complication or effect of
      voluntary sterilization (female) is "post tubal sterilization syndrome". The term
      post tubal sterilization syndrome has been used variously to include abnormal
      menstrual bleeding, dysmenorrahoea, premenstrual distress, hysterectomy and
      miscellaneous other conditions like need for recanalisation, feeling of regret
      and menopausal syndrome. Abnormal vaginal bleeding due to ovarian dysfunction has
      been a regular and common complaint of the female clients after their TS. This
      study was carried out in a clinic setting to find out the level of satisfaction
      among the cases of VS. Level of satisfaction was measured by whether the client
      regretted the procedure, whether their menstrual pattern was changed after the
      procedure, performed either by themselves or VSC by the husband and also by
      finding out how many of them needed hysterectomy and recanalisation procedure.
      Women who had undergone TS were taken as the cases (group A) and those women
      whose husband has VSC were taken as control group (group B). The result showed
      that there is almost no difference in the age group of both case and control at
      the time of their consultation. At the time of VS almost 60% (56.53%) of cases
      were <29 years of age and >70% (71.23%) of the women were <29 years of age when
      their husbands were vasectomised. 26.15% of the women in group A were in the age
      group of 30-40 whereas this age group comprised of only 15.38% in group B.
      Average age at menarche was 14 years and average age at marriage 17 years. The
      menstrual pattern was not found to have changed in both groups excepts for those
      who had organic condition. Hysterectomy had been performed in only 5 cases at the
      age of 30, 34, 40, 42 and 43 years in group-A and in two case in group-B.
      Indications of hysterectomy n these cases were (DUB) and fibroids. Two patients
      in group-A had to undergo recanalisation but the indication in both the cases
      were loss of previous children.

PMID- 16583969
TI  - Histomorphologic pattern of skin lesions in Kathmandu Valley: a retrospective
      study.
AB  - A total of 85 skin biopsies were analyzed to see the pattern of skin disorders in
      Kathmandu Valley. Clinico-histopathological correlation was done to see for the
      inconsistency between clinical and histopathological diagnosis and also to
      analyse for the false positive diagnosis of melanoma in such lesions. The age of
      the patients ranged from 10 to 88 years. No gender predominance was observed.
      Five percent of the lesions were located on head and neck region and rest were
      distributed over chest, back and extremities. Clinically 21 (24.7%) out of 85
      cases showed hyperpigmentation and were diagnosed as melanocytic lesions.
      Intradermal nevus emerged as the single largest disorder with a total of 11 cases
      (12.9%). Capillary hemangioma cases constituted the second largest group with a
      total of 9 cases (10.6%). Seborrhoeic Keratosis (8.2%), Verrucous vulgaris (8.2%)
      Neurofibroma (7.1%), Nonspecific granulomatous lesions (4.7%) and melanoma (3.5%)
      formed the other major groups of disorders. Morphea (1.2%), Psoriasis (1.2%) and
      fungal lesions (1.2%) commonly seen in other studies were not found to be common
      among the skin disorders in the present study.

PMID- 16583970
TI  - Study on etiological factors on mental retardation in Kathmandu.
AB  - The study of etiological factors on mental retardation was conducted at family
      counselling and resource school of Association of Welfare of Menta+lly Retarded
      (AWMR), Hattisar, Kathmandu. A total of 91 mental retarded cases were studied in
      the year 2000 and 2001 for etiological factors. The present study shows
      significant relationship of mental retardation and age in both the year. The
      higher rate of mental retardation in the 0 to 5 years age group in both the year.
      About 70.0% with mental retardation (MR) are first born babies in both the year.
      Majority of the families have unfavourable attitude towards the mentally retarded
      individual.

PMID- 16583971
TI  - Small-scale study on intestinal parasitosis in a remote hilly village in Nepal.
AB  - A small-scale cross sectional study on intestinal parasitosis was conducted in a
      remote hilly village in western Nepal in January 2001. Stool samples collected
      from 115 inhabitants (M: 41 and F: 74; Aged: 1 to 89 years) were examined by
      direct smear method in duplicate. Overall positive rate was 27.0% with a
      marginally high positive rate in males (P>0.05). Dalits (the lower caste people)
      had highest prevalence (71.4%) than Tibeto-Burman and Indo-Arvan ethnic (P>0.05).
      Higher prevalence was observed in adults than in children. Eighty percent of
      subjects had single parasite infection. Altogether, six types of parasites were
      detected of which Ascaris lumbricoides was most common. People having toilet had
      marginally low positive rate. All subjects included in this study were drinking
      raw water. Occupation wise, farmers had marginally high prevalence.

PMID- 16583972
TI  - Genital prolapse in women of Bhaktapur, Nepal.
AB  - Genital prolapse is one of the commonest reproductive morbidity in developing
      country. Common predisposing factors are multiparity, early postpartum sternous
      activity, advanced age and menopause. This study conducted in Bhaktapur district
      in five months included 1337 women aged 20 and above. The prevalence of female
      genital prolapse found to be 7.55%. Maximum numbers of women were having children
      eight and more (48.51%). Only 1.9% of women with genital prolapse were
      nulliparous. Home delivery is still common in Bhaktapur, 79% of women with
      genital prolapse had all children born at home without help. Regarding post
      partum activity majority of them (64.3%) told that they took rest at least one
      month after delivery but 26.73% started working in field in 2-3 weeks after
      delivery. The use of pessary is 25% among female with genital prolapse but only a
      few were following medical advice to change the ring. Nine women were having
      impacted ring in situ for years.

PMID- 16583973
TI  - Menstrual pattern and abnormalities in the high school girls of Dharan: a cross
      sectional study in two boarding schools.
AB  - Puberty is the biological transition between the immature and adult reproductive
      function. This study has been carried out to find out the menstrual pattern, and
      awareness of the abnormalities in menstrual pattern among school going pubertal
      age group girls in Dharan. It has been carried out with the aim to follow it with
      school health education. Cross sectional study was done in 96 girls of two
      different school of Dharan of the age group ranging from 11 years to 17 years.
      The median age of menarche was 12 years. There were 6.9% cases of oligomennorhea
      and 10.0% of hypomenorhea. Menorrhagia was seen in 6.2% of the girls. Spasmodic
      dysmenorrhea was seen in 67.0% of the girls but the daily activity was hampered
      only in 20.0%. Out of the 96 students 73.0% were prepared psychologically
      beforehand. Very less students (8.0%) knew only very little about the
      abnormalities in menstruation, rest were ignorant about it. Thus, it was seen
      that these school going girls needed education about the abnormalities of
      menstruation so that they can differentiate the normal phenomenon from
      abnormality and report in time in case of aberrance in the menstrual cycle.

PMID- 16583974
TI  - Lower respiratory tract infection in infancy in relation to feeding pattern.
AB  - OBJECTIVE: To assess the relation between lower respiratory tract infection and
      feeding pattern in infancy. SETTING: Hospital based descriptive. METHODS: Two
      hundred and five infants presenting with lower respiratory infection (LRTI)
      admitted in the ward were studied over a period of one year. Criteria for the
      clinical diagnosis of LRTI were based on the lines of TUCSON CHILDREN RESPIRATORY
      STUDY. RESULTS: Forty three percent of LRTI in infancy were seen in age group of
      0 to 3 months. Sixty percents of pre-lacteal feeding and 71% of bottle-feeding
      were observed. Late introduction of solid food was very commonly practiced. In
      64.7% solid food was introduced at the age of 9 to 12 months. Fifty three percent
      of LRTI were associated with diarrhoea, which was the commonest factor associated
      with mortality due to LRTI. There was male preponderance with male:female =
      2.8:1(P value <0.001), which is highly significant. Mixed feeding/artificial
      feeding had more incidence of LRTI than exclusively breast-fed children (1.7:1)
      and the mortality rate was 10 times more in mixed/artificial fed infants than
      exclusively breast fed infants.

PMID- 16583975
TI  - Kartagener's syndrome--a case report.

PMID- 16583976
TI  - Online medical journals: need of the hours.
AB  - Online publication of the medical journals over the Internet saves time, cost and
      resources. This allows rapid incorporation of major advances in medical practice.
      Unlike conventional print media, e-journals permit multimedia enhancement of
      medical journal articles. It also makes it feasible, publication of negative
      studies that will enable more accurate appraisals of new studies.

PMID- 16583977
TI  - Role of mind in health and disease (mind-body medicine).

PMID- 16583978
TI  - New variant Creutzfeldt-Jakob disease: a controversial but potential blood
      transfusion risk.

PMID- 16583979
TI  - Statistical evaluation in research.

PMID- 16583980
TI  - Comparison of the effect of the R2 phenothiazine ring substituent on fluphenazine
      and perphenazine interactions with cyclodextrins.
AB  - The effect of -CF3 R2 fluphenazine (FLF) and -Cl R2 perphenazine (PF)
      substituents on interactions of these phenothiazine derivatives with
      cyclodextrins (CD) was compared. Inclusion complexes of protonated and basic
      forms of FLF and PF with CDs were obtained in HCl 0.01 mol/L (pH 1.9 or 2.1), in
      phosphate buffer (pH 5.8) and in Britton-Robinson's buffer (pH 10.2) solutions
      and studied using spectral method. It was established. that the uncharged forms
      of both phenothiazine derivatives interact with CDs stronger than protonated
      molecules and that the perphenazine-CD inclusion complexes characterize greater
      apparent stability constants in comparison to adequate fluphenazine complexes.
      The thermodynamic parameters, estimated from linear Van't Hoff plot, suggest that
      the van der Waals forces accompanied by hydrophobic effects were operating in the
      investigated FLF-CD and PF-CD systems. The effect of pH and presence of CD on
      photostability of FLF or PF was also compared. The photochemical decomposition of
      both phenothiazine derivatives, in the absence and in the presence of CDs,
      proceeds according to the first order reaction. It was also established that
      independent on the charge of molecule, perphenazine was more stabile than
      fluphenazine and that the inclusion complexation with CDs improved the
      photostability of both drugs. The data of 2D NMR analysis suggest, that the
      aromatic portion of FLF and PF molecules, without R2 substituent, tend to the
      interior of CD.

PMID- 16583982
TI  - High-performance liquid chromatographic identification of flavonoid
      monoglycosides from Prunus serotina ehrh.
AB  - Five minor flavonoid monosides, glycosides of quercetin and kaempferol, together
      with three previously isolated compounds were identified cochromatographically in
      P. serotina Ehrh. leaves and flowers (inflorescences) using RP-HPLC and TLC
      techniques and finally determined as quercetin 3-O-alpha-L-arabinofuranoside
      (avicularin), 3-O-alpha-L-arabinopyranoside (guaijaverin), 3-O-beta-D
      xylopyranoside (reynoutrin), 3-O-beta-D-glucopyranoside (isoquercitrin), 3-O-beta
      D-galactopyranoside (hyperoside) followed by kaempferol 3-O-alpha-L
      arabinofuranoside (juglanin), 3-O-beta-D-xylopyranoside and 3-O-beta-D
      glucopyranoside (astragalin). Moreover, two further minor flavonols were isolated
      from the leaves, characterized by hydrolysis experiments, UV and 1H NMR
      spectroscopy, and identified finally as isorhamnetin 3-O-alpha-arabinofuranoside
      and isorhamnetin 3-O-beta-xylopyranoside, the rare natural products.

PMID- 16583981
TI  - Activities of cytosolic aldehyde dehydrogenase isozymes in colon cancer:
      determination using selective, fluorimetric assays.
AB  - Activities of two principal cytosolic forms of human aldehyde dehydrogenase,
      ALDH1A1 and ALDH3AI in colon tumor homogenates and surrounding tissue fragments
      were measured, using isozymeselective, fluorimetric assays. The assays are based
      on two fluorogenic substrates, 6-methoxy-2-naphthaldehyde and 7-methoxy-l
      naphthaldehyde, and are independent of NADH determinations. The results show high
      variability of ALDH levels in colon tumors, with several samples below
      sensitivity level (< 0.01 units per gram protein), while the highest activities
      of both ALDH1A1 and ALDH3A1 in tumor tissue were close to 0.5 U/g. Correlation
      coefficients between tumor and colon tissue activities were found to be below 0.5
      for both ALDH activities examined, but the average activities were similar. and
      close to 0.1 U/g. thus similar to that found in the thyroid fragments. It is
      concluded that ALDH probably cannot be directly responsible for oxazaphosphorine
      resistance in colon cancer.

PMID- 16583983
TI  - Synthesis and biological action of 1-aminomethyl derivatives of 3-R-4-phenyl
      delta2-1,2,4-triazoline-5-thione.
AB  - 4-Phenyl-1,2,4-triazoline-5-thione [I] and 4-phenyl-3-(pyridin-3-yl)-1,2,4
      triazoline-5-thione [II] were subjected to the reaction of aminomethylation with
      piperazine derivatives. Compounds [III] and [IX] were screened for their
      antibacterial activities.

PMID- 16583984
TI  - Aromatic oligopeptides with chlorambucil moiety--synthesis and biological
      evaluation.
AB  - New aromatic oligopeptides with chlorambucil moiety have been synthesized. They
      showed antiproliferative and cytotoxic effect in the standard cell line of the
      mammalian tumor MCF-7.

PMID- 16583985
TI  - Lipophilicity, antifungal and antioxidant properties of persilben.
AB  - The lipophilicity of persilben, an important parameter influencing the
      penetration of the compound through biological membranes, was determined
      experimentally by dynamic method and was theoretically calculated according to
      the fragmentation methods introduced by Crippen, Broto and Viswanadhan. The
      higher value of partition coefficient (log P = 3.89) obtained for persilben than
      that for resveratrol points to potentially higher ease of penetration of
      persilben into cells of living organism. Antimicrobial and antioxidant activities
      of persilben were tested. The obtained data suggest that this compound possesses
      some antioxidant activity. Persilben appears to have also some inhibitory effect
      against some species of dermatophytes from Tnichophyton genus but only at high
      concentrations.

PMID- 16583986
TI  - Investigation of the essential oils from three Cephalotaxus species.
AB  - Essential oils from leaves of Cephalotaxus fortunei Hook., Cephalotaxus
      haningtonia K. Koch., Cephalotaxus sinensis Li. and variety Cephalotaxus
      harringtonia var. drupacea Koidz. underwent qualitative and quantitative
      analysis. The content of the oils obtained by hydrodistillation in the
      investigated species was 0.01 - 0.22% v/w. Gas chromatography (GC-MS) with flame
      ionisation detector (FID) showed generally 47 components in the essential oils.
      In all investigated species the presence of a-pinene varying from 18.4% to 35.1%,
      as well as sesquiterpene hydrocarbon beta-caryophyllene up to 22% at Cephalotaxus
      fortunei were revealed as the main components.

PMID- 16583987
TI  - Microemulsions as potential ocular drug delivery systems: phase diagrams and
      physical properties depending on ingredients.
AB  - The microemulsion systems, both o/w and w/o, composed of isopropyl myristate,
      soybean lecithin (Epikuron 200), Polysorbate 80, Cremophor EL, n-butanol and
      triacetine, taken at various amounts and in various combinations, were tested in
      order to assess their physical-chemical properties. Some ingredients of the
      microemulsions were physiologically acceptable, except one formulation containing
      n-butanol used as a model reference system. Phase diagrams were made for all
      microemulsions studied in order to test the influence of components on the
      boundaries of the stable microemulsion domains. The greatest area of stable
      microemulsion system was obtained for the formulation in which n-butanol was
      used, while the smallest area was obtained when soybean lecithin (Epikuron 200)
      was used as a surfactant. The following physical parameters were analyzed:
      osmotic tension, density, viscosity, refractive index. pH and particle size.
      Microemulsions stored at 25 degrees C for the period up to 12 months, showed
      physical changes depending on ingredients. The study made it possible to select
      the most stable microemulsion system meeting the requirements of eye drops.

PMID- 16583988
TI  - B16 and cloudman S91 mouse melanoma cells susceptibility to apoptosis after
      dacarbazine treatment.
AB  - Considering the necessity of an individual choice of cytostatic drugs for
      patients with cancer disease and tumor cells' resistance to these compounds,
      their ability to induction of apoptosis should be investigated. The aim of this
      study was to determine the influence of dacarbazine (DTIC) on morphology and
      kinetics of proliferation of B16 and Cloudman S91 cells. It is important to
      determine the kind of death induced by the DTIC and the effect of a specific
      concentration. The evaluation of apoptosis and necrosis in these two mouse
      melanoma cell lines in vitro was performed. Induction of apoptosis was estimated
      in annexin V binding assay by flow cytometry. DNA content and cell cycle phases
      were determined by propidium iodide staining. DTIC induced morphological changes
      typical for apoptosis and necrosis in both cell lines. DTIC caused cell cycle
      arrest in S and G2/M phase of both cell lines which showed hypertetraploidy. The
      highest induction of apoptosis was observed in DTIC concentration of 200
      microg/mL for B16 cells (11%) and 100 microg/mL for apoptosis Cloudman S91 cells
      (22.2%). Higher doses of DTIC caused intensification of necrotic process. The B16
      melanoma cells are more sensitive to DTIC than the Cloudman S91 cells, however
      more intensive apoptotic process was detected in Cloudman S91 cells already at
      lower concentration of DTIC.

PMID- 16583989
TI  - Economic impact of standard antibiotic therapy combined with amikacin, in
      clinical unit, Lodz, poland--part I.
AB  - The study "Alexander" on bacterial resistance to antibiotics conducted in Poland
      revealed high sensitivity of bacterial strains to simple and cheap antibiotics.
      In Poland pharmacoeconomic studies on the safety, effectiveness and costs of
      treatment are rare. Development of therapeutic standards in bacterial infections
      on the basis of pharmacoeconomic analyses and clinical studies determining
      effectiveness and safety of therapy allows for more rational pharmacotherapy. The
      following problems were investigated: is the treatment of serious bacterial
      infections with cheap standard antibiotics [SAT] or other antibiotics therapy
      [OAT] combined with amikacin safe and effective? What are the direct costs? How
      can reduction in costs be achieved? Prospective, randomized, single-blind study
      was performed in the group of 152 patients, admitted from 1 January to 31 July
      2000, treated with amikacin combined with aminopenicillin/amoxicillin [SAT]
      versus other antibiotic therapy [OAT]. The economic evaluation was done by
      estimation of direct cost of treatment in patients with risk factors of
      nephrotoxicity [NT] and therapeutic drug monitoring [TDM] versus without TDM. The
      statistical significance was evaluated. This study revealed that effectiveness of
      the SAT versus OAT combined with amikacin in serious infections is high, 80% vs.
      87%, respectively. Amikacin used in high once daily dose [HODD] in combined
      therapy with SAT or OAT was more safe in patients with risk of nephrotoxicity and
      TDM (21%) vs without TDM (10%) than used in conventional therapy [CT] 40% vs 19%
      [p < 05]. Evaluation of the absolute risk of nephrotoxicity increase in patients
      with TDM was 0.16 vs 0.34 Absolute Risk Increase (ARI) 0.18, Relative Risk
      Reduction (RRR): 0.53; 95% Confidence Interval (Cl): 0.87-2.82. The number needed
      to tread (NNT): 5.43; reduction of the risk of nephrotoxicity in patients without
      TDM treated with HODD was 0.19 vs 0.09, Absolute Risk Reduction (ARR): 0.09; RRR:
      0.47; 95% CI: 0.74-1.34; NNT: 11.1; reduction of the risk of nephrotoxicity in
      patients with TDM treated with amikacin HODD was 0.21 vs 0.40, ARR: 0.19; RRR:
      0.48; 95% CI 0.68-1.74; NNT: 5.3; Direct costs of the treatment with SAT vs OAT
      combined with amikacin are low [EU 78.30 vs EU 145.16] in the Clinical Unit of
      Lodz, compared with other countries. Out of EU 530 for the hospitalization of one
      patient, 86% constituted "hotel costs". Omitting TDM in patients without risk
      factors can significantly decrease costs by EU 66 860 per 1000 patients.
      Introduction of safe and cheap standard in the treatment of bacterial infections
      in clinical unit, shortening hospitalization by 5 days and limiting the number of
      patients requiring TDM service allows for a decrease in direct cost of about EU
      235410 per 1000 patients/year.

PMID- 16583990
TI  - Economic impact of standard antibiotic therapy combined with amikacin, in
      clinical unit, Lodz, Poland--part II.
AB  - The study "Alexander" on bacterial resistance to antibiotics conducted in Poland
      revealed high sensitivity of bacterial strains to simple and cheap antibiotics.
      In Poland pharmacoeconomic studies on the safety, effectiveness and costs of
      treatment are rare. Development of therapeutic standards in bacterial infections
      on the basis of pharmacoeconomic analyses and clinical studies determining
      effectiveness and safety of therapy allows for more rational pharmacotherapy. The
      following problems were investigated: is the treatment of serious bacterial
      infections with cheap standard antibiotics [SAT] or other antibiotics therapy
      [OAT] combined with amikacin safe and effective? What are the direct costs? How
      can reduction in costs be achieved? Prospective, randomized, single-blind study
      was performed in the group of 152 patients, admitted from 1 January to 31 July
      2000, treated with amikacin combined with aminopenicillin/amoxicillin [SAT]
      versus other antibiotic therapy [OAT]. The economic evaluation was done by
      estimation of direct cost of treatment in patients with risk factors of
      nephrotoxicity [NT] and therapeutic drug monitoring [TDM] versus without TDM. The
      statistical significance was evaluated. This study revealed that effectiveness of
      the SAT versus OAT combined with amikacin in serious infections is high, 80% vs.
      87%, respectively. Amikacin used in high once daily dose [HODD] in combined
      therapy with SAT or OAT was more safe in patients with risk of nephrotoxicity and
      TDM (21%) vs without TDM (10%) than used in conventional therapy [CT] 40% vs 19%
      [p < 05]. Evaluation of the absolute risk of nephrotoxicity increase in patients
      with TDM was 0.16 vs 0.34 Absolute Risk Increase (ARI) 0.18, Relative Risk
      Reduction (RRR): 0.53; 95% Confidence Interval (CI): 0.87-2.82. The number needed
      to tread (NNT): 5.43; reduction of the risk of nephrotoxicity in patients without
      TDM treated with HODD was 0.19 vs 0.09, Absolute Risk Reduction (ARR): 0.09; RRR:
      0.47; 95% CI: 0.74-1.34; NNT: 11.1; reduction of the risk of nephrotoxicity in
      patients with TDM treated with amikacin HODD was 0.21 vs 0.40, ARR: 0.19; RRR:
      0.48; 95% CI: 0.68-1.74; NNT: 5.3; Direct costs of the treatment with SAT vs OAT
      combined with amikacin are low [EU 78.30 vs EU 145.16] in the Clinical Unit of
      Lodz, compared with other countries. Out of EU 530 for the hospitalization of one
      patient, 86% constituted "hotel costs". Omitting TDM in patients without risk
      factors can significantly decrease costs by EU 66 860 per 1000 patients.
      Introduction of safe and cheap standard in the treatment of bacterial infections
      in clinical unit, shortening hospitalization by 5 days and limiting the number of
      patients requiring TDM service allows for a decrease in direct cost of about EU
      235410 per 1000 patients/year.

PMID- 16583991
TI  - Preparation, structure and affinity for imidazoline I2 receptors and alpha2
      adrenoceptors of 1-[(4,5-dihydroimidazolidin-2-yl)imino]indan-2-ols.
AB  - Two enantiomers IR, 2S-(+)-cis (3a) and IS, 2R-(-)-cis (3b) of 1-[(4,5
      dihydroimidazolidin-2-yl)imino]indan-2-ol were prepared by reacting 2-chloro-4,5
      dihydroimidazole (1) with corresponding 1-amino-indan-2-ols (2a-b). The compounds
      obtained are structural analogues of PMS 952 agent containing imino bridge in
      place of methylene group. Compound 3a exhibited moderate almost equal activity at
      both imidazoline I2 receptors and alpha2-adrenoceptors, while enantiomer 3b was
      found to be selective for alpha2-adrenoceptors (alpha2/I2 selectivity ratio =
      10.4).

PMID- 16583992
TI  - An updated and further developed theory and evidence for the close-contact, one
      on-one association of nearly all cell K+ with beta- and gamma-carboxyl groups of
      intracellular proteins.
AB  - The primary focus of this communication is to present an updated and advanced
      version of the theory of close-contact association of molecules and ions through
      the spatial fixation and aggregation of the adsorbing sites. The last sections of
      the text also review a collection of relevant in vitro and in vivo experimental
      findings gathering since seventy years ago. Though some of these findings were
      published before the theory, old and new, they all support the theory that close
      contact association with the beta-, and gamma-carboxyl groups of intracellular
      proteins causes the selective accumulation of potassium ions (K+) in living
      cells.

PMID- 16583993
TI  - Studies on the amount of aluminum and calcium in urine following aluminum
      administration with and without amino acids.
AB  - The evidence implicating aluminum as a neurotoxin is mounting. Research with
      animals and humans has linked aluminum with neuro-cognitive dysfunction and, in
      some cases, death. Although the relationship between aluminum intake and
      Alzheimer's disease is still unclear, some experts have recently issued a strong
      warning that human exposure to aluminum should be limited. The results indicate
      that the amount of aluminum decreased in the urine in mice that were administered
      glycine or glutamic acid together with aluminum ion. In the mice in which the
      amounts of aluminum decreased in the urine, the amount of calcium conversely
      increased.

PMID- 16583994
TI  - Electrical properties of hornet silk: temperature dependence.
AB  - Hornet silk is a polymer of amino acids. One of the known properties of polymers
      is their electrical activity. The present study describes the results of
      electrical measurements carried out vertically on the silk cap of pupae of the
      Oriental hornet Vespa orientalis (Hymenoptera, Vespinae). The measurements
      undertaken were the temperature-dependent electric current, voltage and
      resistance, all measured within the range of biological temperatures, as well as
      the capacitance. The temperature-dependent spontaneous current attained values up
      to 327 nano Amperes (nA) while the maximal voltage reached 347 millivolt (mV).
      The electrical resistance was low and steady (1-20 mu omega) at temperatures
      ranging between 19-32 degrees C, but at lower or higher temperature it increased
      fairly sharply by about three orders of magnitude. The electrical capacitance,
      computed according to the discharge curve (decay curve) amounted to 0.4
      microFarad (microF). The paper also discusses the role of the pupal silk as
      producer of a 'clean room' while the cuticle is being laid down by the pupae
      after undergoing metamorphosis, as well as the significance of the measured
      electrical parameters vis-a-vis the developing pupae.

PMID- 16583995
TI  - Effect of alternating electromagnetic field on early stages of plant development.

PMID- 16583996
TI  - Specific spatial organization of chromosomes in nuclei of primary human
      fibroblasts is maintained by nuclear matrix.

PMID- 16583997
TI  - A rapid nongenomic effect of aldosterone on intracellular sodium concentration in
      the distal nephron segment of the rat.

PMID- 16583998
TI  - A new manifestation of radiation adaptive response: low doses of ionizing
      radiation decrease serum DNA content under subsequent irradiation of mice in vivo
      with a high doze.

PMID- 16583999
TI  - Functional invariant approach to the biological system uniqueness: a simple
      neuronet model.

PMID- 16584000
TI  - The lipopolysaccharide of Rh. capsulatus suppresses the endotoxin-induced delay
      of apoptosis of human myeloid cells.

PMID- 16584001
TI  - Luminescence detection of tightly bound stacking aggregates of adenine and
      adenosine in aqueous solutions--the candidates for the role of the first genetic
      templates.

PMID- 16584002
TI  - Cholinergic activity of isoquinoline alkaloids from the showy autumn crocus
      (Colchicum speciosum Stev.).

PMID- 16584003
TI  - Comparison of functional parameters of constitutive and hypoxia-induced
      expression plasmids during acute ischemia of lower extremities.

PMID- 16584004
TI  - Inhibition of callose hydrolysis by salicylic acid interferes with tobacco mosaic
      virus transport.

PMID- 16584005
TI  - Spectral and temporal dynamics of transitional processes in the reaction centers
      of Rhodobacter sphaeroides in the region of 780-830 nm.

PMID- 16584007
TI  - Sir Nigel resigns, admitting 'accountability' for cash crisis.

PMID- 16584006
TI  - Production of recombinant antitumor antibodies by HEK-293 cells.

PMID- 16584008
TI  - Crisp regisnation. 'I have to think about what's best'.

PMID- 16584009
TI  - Cash crisis is slowing down reform, Hewitt admits.

PMID- 16584010
TI  - Practice-based commissioning. The paradox at the heart of practice power.

PMID- 16584011
TI  - On the brutal beauty parade.

PMID- 16584012
TI  - Barometer. PCTs Feb 2006.

PMID- 16584013
TI  - Joint working. Framework for success.
AB  - PCTs and councils can improve commissioning through shared agreements setting out
      local priorities. The enhanced role of local authority directors of adult social
      services will play a key role. One successful example of joint working is in
      Southwark, which has joint appointments for senior health and social services
      commissioning roles.

PMID- 16584014
TI  - On primary care.

PMID- 16584015
TI  - On doctors and management.

PMID- 16584016
TI  - Contracting. Learning to love.
AB  - Despite a chequered history, the NHS and independent sector must learn to get
      along if new commissioning processes are to be effective. Nationally standardised
      data on patients, conditions and referrals, and fair performance review
      structures, would help facilitate this.

PMID- 16584017
TI  - Primary care. A problem shared.

PMID- 16584018
TI  - Salary survey. Women still suffer on pay.

PMID- 16584019
TI  - In Europe, bird flu hits home.

PMID- 16584020
TI  - Emerging epidemic. Decades after hiding out in millions of bodies, the hepatitis
      C virus is ready to rock and kill.

PMID- 16584021
TI  - Bush budget calls for Medicare cuts of dollar 36 billion over five years.

PMID- 16584022
TI  - Skin in the game.

PMID- 16584023
TI  - Seniors deserve Medicare extension.

PMID- 16584024
TI  - Diagnostic tests for hyperthyroidism in cats.
AB  - The diagnosis of hyperthyroidism, one of the most common disorders affecting
      elderly cats, is usually straightforward and considered routine by most
      practitioners. Nowadays, however, most cats suffering from hyperthyroidism tend
      to be diagnosed earlier and at a milder stage of the disease than those cats
      diagnosed 10 to 25 years ago. There are, in fact, a growing number of cats with
      clinical signs of hyperthyroidism and palpably large thyroid glands whose
      baseline serum total thyroid hormone concentrations are within the normal or
      borderline range, making diagnosis problematic. This paper reviews the available
      tests used to confirm a diagnosis of hyperthyroidism in cats and discusses their
      overall usefulness.

PMID- 16584025
TI  - Thyroid scintigraphy in hyperthyroidism.
AB  - Thyroid scintigraphy is a nuclear medicine procedure that produces a visual
      display of functional thyroid tissue based on the selective uptake of various
      radionuclides by thyroid tissue. Thyroid scintigraphy provides valuable
      information regarding both thyroid anatomy and physiology and can play an
      integral role in the diagnosis and management of cats with hyperthyroidism.
      Thyroid scintigraphy allows the direct visualization of the functional
      adenomatous thyroid tissue responsible for the development of hyperthyroidism.
      For this reason, thyroid scintigraphy will allow the diagnosis of hyperthyroidism
      before laboratory tests are consistently abnormal. Thyroid scintigraphy can also
      exclude a diagnosis of hyperthyroidism in cats with thyroid hormone elevations of
      nonthyroidal origin. Thyroid scintigraphy provides an additional method for
      determining the relative severity of thyroid disease that is less affected by the
      presence of concurrent nonthyroidal illness than laboratory evaluations. When
      treating hyperthyroid cats with radioiodine, the lowest effective dose should be
      administered. In an effort to administer the lowest radioiodine dose possible,
      the volume of adenomatous thyroid tissue present in the individual hyperthyroid
      cat should be considered. Thyroid scintigraphy provides an excellent method for
      evaluating the size of hyperfunctional thyroid tissue that is not limited by the
      presence of ectopic or intrathoracic thyroid tissue. Thyroid scintigraphy also
      provides valuable information in the diagnosis and evaluation of hyperthyroid
      cats with thyroid carcinoma.

PMID- 16584026
TI  - Hyperthyroidism and the kidney.
AB  - Hyperthyroidism and chronic renal failure (CRF) are both common diseases of older
      cats. Hyperthyroidism increases GFR by a variety of physiologic effects. Chronic
      renal failure can suppress total T4 concentrations in cats with concurrent
      hyperthyroidism, and free T4 is not a useful distinguishing test. Medical therapy
      (ie, methimazole) is recommended in cats with pre-existing CRF. Overt renal
      failure occurs in approximately 30% of cats treated for hyperthyroidism. It
      usually occurs within one month of treatment and tends to remain mild and stable
      over time. There is no practical way to predict which cats will develop CRF after
      treatment of hyperthyroidism, although GFR measurement does seem useful.

PMID- 16584027
TI  - Medical management of hyperthyroidism.
AB  - Radioiodine is considered the treatment of choice for hyperthyroidism, but in
      some situations, methimazole therapy is preferred, such as in cats with pre
      existing renal insufficiency. Methimazole blocks thyroid hormone synthesis, and
      controls hyperthyroidism in more than 90% of cats that tolerate the drug.
      Unfavorable outcomes are usually due to side effects such as gastrointestinal
      (GI) upset, facial excoriation, thrombocytopenia, neutropenia, or liver enzyme
      elevations; warfarin-like coagulopathy or myasthenia gravis have been reported
      but are rare. Because restoration of euthyroidism can lead to a drop in
      glomerular filtration rate, all cats treated with methimazole should be monitored
      with BUN and creatinine, in addition to serum T4, complete blood count, and liver
      enzymes. Transdermal methimazole is associated with fewer GI side effects, and
      can be used in cats with simple vomiting or inappetance from oral methimazole.
      Hypertension may not resolve immediately when serum T4 is normalized, and
      moderate to severe hypertension should be treated concurrently with-atenolol,
      amlodipine, or an ACE inhibitor. Alternatives to methimazole include carbimazole,
      propylthiouracil, or iodinated contrast agents.

PMID- 16584028
TI  - Thyroidectomy in the cat.
AB  - Thyroidectomy in cats is most commonly indicated to treat hyperthyroidism because
      of adenomatous hyperplasia of the thyroid glands. Preoperative stabilization of
      the hyperthyroid cat with antithyroid drugs is preferred to minimize anesthetic
      and surgical complications. Multiple surgical techniques for thyroidectomy have
      been reported, and results of surgery and complications differ between
      techniques. The extracapsular technique offers the most complete removal of
      abnormal thyroid tissue, while still being associated with a low incidence of
      postoperative hypoparathyroidism. Important postoperative considerations are to
      carefully monitor serum calcium concentrations and treat hypocalcemia if
      necessary, and to monitor the cat for evidence of relapse of hyperthyroidism.

PMID- 16584029
TI  - Radioiodine treatment of hyperthyroidism.
AB  - Radioactive iodine provides a simple, effective, and safe treatment for cats with
      hyperthyroidism and is regarded by most authorities to be the treatment of
      choice. It is a particularly useful treatment for cats with bilateral thyroid
      involvement (found in approximately 70% of cats), cats with ectopic
      (intrathoracic) thyroid tissue, and the rare patient with thyroid carcinoma.
      Treatment with radioiodine avoids the inconvenience of daily, oral administration
      of an antithyroid drug, as well as the side effects commonly associated with
      these drugs. Use of radioiodine also avoids the risks and perioperative
      complications associated with anesthesia and surgical thyroidectomy. Radioiodine
      treatment involves a single, nonstressful procedure that is without associated
      morbidity or mortality. A single treatment restores euthyroidism in most cats
      with hyperthyroidism. Whereas the therapy is simple and relatively stress-free
      for cats, it does require special licensing and hospitalization facilities,
      nuclear medicine equipment, and extensive compliance with local and state
      radiation safety laws.

PMID- 16584030
TI  - Diagnosis of congenital and adult-onset hypothyroidism in cats.
AB  - Whereas hyperthyroidism is the most common endocrine disorder in the cat,
      hypothyroidism is the least common feline endocrine disorder. This is a the
      result of several factors including low index of suspicion, rarity of the
      naturally occurring hypothyroidism in cats, and a lack of species specific tests
      for endogenous TSH and antithyroglobulin antibodies. Nonetheless, hypothyroidism
      does occur in cats, especially in kittens and after radioactive treatment for
      hyperthyroidism. The clinician should become familiar with the common
      presentations of congenital and adult-onset hypothyroidism in cats. In addition,
      some of the tests specific to dogs (such as endogenous canine TSH) may be
      utilized to diagnose subclinical hypothyroidism in cats. Fortunately, the
      treatment of feline hypothyroidism with synthetic levothyroxine is both
      straightforward and effective.

PMID- 16584031
TI  - Bill proposes EHRs for all federal employees, ties funding to performance.

PMID- 16584032
TI  - Hospices may get higher payments at beginning, end of stays.

PMID- 16584033
TI  - Lacking audit trails could render EHRs moot in court.

PMID- 16584034
TI  - [Child health record and certificates. New models].

PMID- 16584035
TI  - [Orphan diseases, rare diseases, time to get mobilised].

PMID- 16584037
TI  - [Wegener's granulomatosis].

PMID- 16584036
TI  - [Ondine syndrome or central congenital hypoventilation syndrome].
AB  - Congenital central hypoventilation syndrome (CCHS) is a rare disease due to a
      severely impaired central autonomic control of breathing and dysfunction of the
      autonomous nervous system. The incidence is estimated to be at 1 of 200,000
      livebirths. A heterozygous mutation of PHOX-2B gene is found in 90% of the
      patients. Association with a Hirschsprung's disease is observed in 16% of the
      cases. Despite a high mortality rate and a lifelong dependence to mechanical
      ventilation, the long-term outcome of CCHS should be ultimately improved by
      multidisciplinary and coordinated follow-up of the patients.

PMID- 16584038
TI  - [Postural disorders in children. Reassurance, screening and indications for
      treatment].

PMID- 16584039
TI  - [Musculoskeletal examination: from neonates to adolescents].
AB  - A large number of medical consultations are related to musculoskeletal
      abnormalities. Less than 10 percent of patients are referred for surgery. In most
      cases, history taking and a mere clinical examination are sufficient to establish
      a diagnosis. Useful additional tests are usually limited to standard
      anteroposterior and lateral x-rays and laboratory analysis when an infection- or
      inflammation-induced abnormality is suspected. Any physician likely to deal with
      children should be able to conduct this clinical examination and include some of
      its elements given its essential role in screening (spinal deformities for
      instance).

PMID- 16584041
TI  - [Orthopedic and surgical treatment of idiopathic scoliosis in childhood and
      adolescence].
AB  - Any evolutive scoliosis must be treated actively. The orthopaedic treatment by
      brace makes it possible to slow down the spinal deformity evolution. In many
      cases, physiotherapy could be of great help during the conservative treatment
      phase. Thus, it is possible to contain the scoliosis progression during the rapid
      growth phase of the spine, in adolescence. In some patients, spinal deformity can
      remain moderate, making it possible to keep a satisfying function and balance of
      the spine in adulthood. Sometimes, the orthopaedic treatment alone is not
      sufficient and surgery is necessary to provide a well-balanced spine with an
      acceptable residual spinal deformity. The aims of surgical treatment are to
      correct spinal deformity by means of vertebral osteosynthesis and to stabilize
      the final correction by means of bone grafting. These surgical procedures made
      according to strict rules, give excellent functional results and make it possible
      to carry out a strictly normal adult life.

PMID- 16584040
TI  - [Scoliosis in children].
AB  - The diagnosis of scoliosis is based on the association of kyphosis, vertebral
      rotation, and lateral deviation of the spine. The clinical examination has to be
      rigorous in order to rule out a potential etiology for this tridimensional
      deformity. The assessment of the growth, and of the progressive nature of the
      scoliosis, is essential before any treatment. For minor deformities, a simple
      clinical monitoring will be necessary. On the other hand, for moderate
      deformities, a non-surgical treatment with brace will be recommended. Finally,
      for severe deformities, the treatment will be a surgical treatment. Surgery will
      consist of a spinal arthrodesis.

PMID- 16584042
TI  - [Kyphosis and kyphotic posture in children and adolescents].
AB  - Kyphosis is a sagittal deviation of the spine that presents as an anterior spinal
      curvature. It is a frequent reason for consultation during adolescence. It is
      necessary to know how to differentiate between a simple postural kyphosis that is
      flexible and reducible, and requires no further investigation, from a true
      kyphosis that requires at minimum a radiological evaluation with films of the
      entire spine, in AP and lateral views. If vertebral epiphysitis is most often at
      the origins of the sagittal vertebral deviations encountered in daily practice,
      the other causes pose diagnostic and therapeutic problems that are often more
      complex. They include congenital, paralytic, infectious, cancerous and post
      traumatic kyphosis, or kyphosis due to constitutional bone diseases. Surgical
      treatments, that have only an exceptional place in treatment of the regular
      kyphosis of the adolescent, are potentially indicated in all of the other
      situations.

PMID- 16584043
TI  - ["In-toeing and out-toeing"].
AB  - From birth to the end of growth, a femoral detorsion associated with a lateral
      tibial torsion can be observed. The absence or the exaggeration of this
      phenomenon leads to rotational abnormalities of the lower limbs called by parents
      as " in-toeing or out-toeing ". This represents one of the most frequent motives
      for consultation in pediatric orthopedics. The analysis of the respective
      position of knees and feet during walking and the measurements of femoral and
      tibial torsion allow the diagnosis of rotational abnormalities. During growth,
      the degree of these anomalies may increase or decrease spontaneously. As there is
      no evidence of a relationship between rotational abnormalities and arthritis,
      there are no preventive orthopaedic or surgical treatments. However, at the end
      of the growth, the persistence of functional symptoms leads to femoral or tibial
      derotation osteotomies.

PMID- 16584045
TI  - [Patient handout: monitoring the spine of the child].

PMID- 16584044
TI  - [The limping child with a painful hip].
AB  - Hip pain is a frequent cause for limping in children. Etiology work out is
      oriented by the age of the child, the existence of a traumatic or infectious
      background, the child's morphology and ethnic origin, and most of the diagnoses
      will require only a standard X-ray and an ultrasound to be confirmed. In this
      way, the three main causes to be considered in children of less than 10 years of
      age are septic arthritis, transient synovitis and Perthes disease. Septic
      arthritis will require an urgent treatment, whereas Perthes disease will need a
      long care and follow up in order to watch for a poor outcome that will
      necessitate a surgical treatment to restore containment of the femoral head. In
      the adolescent, especially in case of overweight, the first etiology to be
      considered is slipped femoral capital epiphysis, a condition that requires an
      early and adequate surgical treatment (in situ screw fixation), in order to avoid
      further displacement and femoral head deformity of poor prognosis.

PMID- 16584046
TI  - [To assess: what, how and especially why?].

PMID- 16584047
TI  - [National ranking examination N16. What could fall at the exam?].

PMID- 16584048
TI  - [Testicular tumors].

PMID- 16584050
TI  - [Convulsions in infants and children].

PMID- 16584049
TI  - [Follow-up of patients with artificial cardiac valves and vascular prostheses.
      First part--monitoring patients with artificial valves].

PMID- 16584051
TI  - [Arteriosclerosis obliterans of the aorta and lower limbs. Aneurysm].

PMID- 16584052
TI  - [Multidisciplinary palliative care to patients at the end of life. Support to the
      dying and their families].

PMID- 16584053
TI  - [Mrs. du Coudray's dummy or how to educate midwives in the 18th Century].

PMID- 16584054
TI  - Sticking it to cancer.

PMID- 16584055
TI  - The tribulation of trials.

PMID- 16584056
TI  - Hemoglobinization and functional availability of iron for erythropoiesis in case
      of thalassemia and iron deficiency anemia.
AB  - Microcytic erythropoiesis in case of anemia is frequently due to iron deficiency
      or may be due to alpha- and beta- thalassemia trait as a result of increased
      activity of erythropoiesis. The aim of the present study was to evaluate
      alterations with regard to the degree of hemoglobinization in reticulocytes in
      comparison with mature erythrocytes. Iron availability in subjects with anemia
      resulting from iron deficiency and alpha- or beta- thalassemia was studied by
      application of conventional as well hemocytometric parameters that have recently
      become available. Participants of the study were reference subjects (n=75),
      subjects with iron deficiency anemia (IDA, n=52) and alpha- (n=26) or beta
      thalassemia trait (n=24). If compared with the reference group obviously
      increased RBC counts together with decreased values for RDW-sd and MCHC were
      established in case of alpha- and beta- thalassemia subjects. Deviations were
      demonstrated to be more pronounced in case of beta- thalassemia. Accelerated
      erythropoiesis in the case of subjects with IDA and beta-thalassemia is
      manifested by detection of increased results for immature reticulocyte counts. In
      particular in case of beta- thalassemia, elevated reticulocyte counts combined
      with slightly increased values for ZPP/heme ratio reflect increased activity of
      erythropoiesis. In the case of subjects with beta-thalassemia serum transferrin
      concentrations revealed slightly decreased results, whereas serum ferritin and
      iron concentrations demonstrated a tendency towards higher values if compared
      with the group of reference subjects. At a definitive MCV level, the hemoglobin
      content of reticulocytes is decreased in the case of IDA if compared with the
      alpha- or beta- thalassemia trait. For the ratio of hemoglobin content of
      reticulocytes and erythrocytes, obviously decreased results are demonstrated in
      the case of subjects with iron deficiency anemia (1.02 +/- 0.08, mean +/- SD) and
      in the case of beta-thalassemia (1.06 +/- 0.04) if compared with the group of
      reference subjects (1.11 +/- 0.02) and a-thalassemia (1.11 +/- 0.07). Evaluation
      of the hemoglobinization state should be performed by means of pattern
      recognition in concordance with characteristic profiles for parameters reflecting
      the actual iron state. In case of therapy the result of intervention can be
      appropriately monitored by longitudinal follow-up.

PMID- 16584057
TI  - The fibrinolytic system in newborns and children.
AB  - The fibrinolytic system comprises a series of serine proteases that interact to
      cleave fibrin into fibrin degradation products. Although all key components of
      the fibrinolytic system are present at birth, important age-dependent,
      quantitative and qualitative differences are present during childhood as compared
      to adults. These differences include decreased plasma concentrations of
      plasminogen, tissue-type plasminogen activator and alpha2-antiplasmin, increased
      plasma concentrations of plasminogen activator inhibitor-1, as well as a decrease
      in both plasmin generation and overall fibrinolytic activity. Increasing evidence
      suggests that these age-dependent differences may contribute to the development
      of specific childhood diseases and influence the course of fibrinolytic therapy,
      particularly in newborns. This review aims to summarize the available information
      on the age-dependent features of the fibrinolytic system in newborns and children
      in healthy and disease states and the impact of these features on fibrinolytic
      therapy.

PMID- 16584058
TI  - Identification of the translocation t(15;17) in acute myeloid leukemia (AML)
      initially classified as FAB M1: case report and review of the literature.
AB  - We report a case of a patient aged about 53 years, who initially presented with
      hematological disorders (WBC: 44000/mm3, Hb: 11g/dl, Pit: 127000/mm3) without
      tumoral syndrome. The Wright-Giemsa stained bone marrow and peripheral blood
      smears showed a population of blast cells characterized by cells with high N/C
      and strongly basophilic cytoplasm without granules. The nuclei were predominantly
      round. Nuclear chromatin was fine and contained small nucleoli. Cytochemisty was
      positive for peroxidase activity. Immunophenotyping showed myeloid typical
      markers of granulocytic lineage (MP0+, CD13+, CD33+, CD117+, CD34-). The
      karyotype revealed the expression of t(15;17) chromosomal translocation. The
      diagnosis of acute myeloid leukaemia (AML) was then evoked initially. The
      cytological features corresponded closely to the M1 subtype as defined in the FAB
      classification. The patient was treated with induction therapy according to the
      7/3 protocol. One month later, he was discharged from hospital on hematological
      and cytogenetic remission. He died at home because of a heart attack. From the
      biological findings the patient was retrospectively diagnosed as having
      promyelocytic leukemia (hyperbasophilic form).

PMID- 16584059
TI  - Folate supplementation does not affect biochemical markers of bone turnover.
AB  - BACKGROUND: Recently, increased plasma homocysteine (HCY) has been suggested as a
      novel independent risk factor for osteoporotic fractures. This study aimed to
      analyze the effect of a HCY lowering therapy by folic acid (FA) supplementation
      on biochemical bone markers in healthy subjects. MATERIAL AND METHODS: We treated
      61 healthy individuals (mean age: 58+/-8 years) with placebo, 0.4, 1 or 5 mg FA
      daily for 2 months. Fasting blood samples were taken after 0, 4 and 8 weeks.
      Serum HCY, folate, vitamin B12, osteocalcin (OC), procollagen type I N-terminal
      propeptide (PINP) and C-terminal telopeptides of human collagen type I (CTX) were
      studied. RESULTS: Overall baseline HCY and folate levels were 13.4 +/- 3.6
      micromol/L and 5.7 +/- 3.0 microg/L, respectively. Participants exhibited normal
      baseline OC, PINP and CTX levels. Serum folate increased during supplementation
      (4 weeks of placebo, 0.4, 1 and 5 mg of FA: -7, +160, +162 and +436 %; 8 weeks: 
      6, +305, +340 and +216 %) and HCY decreased (4 weeks of placebo, 0.4, 1 and 5 mg
      of FA: +2, -14, -21 and -17 %; 8 weeks: +2, -8, -20 and -17 %) in the treatment
      groups, but not in the placebo group. OC (placebo: 22.8 vs. 23.0 vs. 23.6; 0.4 mg
      FA: 21.6 vs. 22.1 vs. 24.1; 1 mg FA: 23.7 vs. 22.6 vs. 23.4; 5 mg FA: 24.1 vs.
      20.5 vs. 20.9 microg/L), PINP (placebo: 43.5 vs. 51.3 vs. 46.5; 0.4 mg FA: 34.0
      vs. 34.1 vs. 39.5; 1 mg FA: 43.6 vs. 39.7 vs. 43.2; 5 mg FA: 41.1 vs. 38.7 vs.
      37.4 microg/L) and CTX (placebo: 258 vs. 360 vs. 321; 0.4 mg FA: 229 vs. 290 vs.
      315; 1 mg FA: 319 vs. 325 vs. 301; 5 mg FA: 293 vs. 321 vs. 304 ng/L) did not
      change throughout the study. CONCLUSION: Short-term FA supplementation does not
      affect biochemical bone markers in non-osteoporotic subjects with a low folate
      status.

PMID- 16584060
TI  - Hyperhomocysteinemia--the biochemical link between a weak heart and brittle
      bones?
AB  - Osteoporosis, chronic heart failure (CHF) and mild to moderate
      hyperhomocysteinemia (HHCY) can frequently be found in elderly individuals and
      often occur in the same individual. Due to demographic changes in the number of
      elderly people the total number of individuals suffering from osteoporosis and/or
      CHF, and hence the cost to society, will increase dramatically over the next 50
      years. Thus, prevention of these diseases by identifying and modifying risk
      factors is a major issue. Recent large population-based prospective studies
      suggested HHCY as an independent risk factor for CHF and osteoporosis. However,
      the mechanisms that link HHCY to CHF and osteoporosis are almost unknown.
      Moreover, until now both diseases have been considered as independent diseases.
      The finding that heart and bones share a common biochemical risk factor raises
      the question if there is a biochemical link between these two diseases? This
      manuscript reviews the existing literature about HHCY and osteoporosis, about
      HHCY and CHF, and about possible mechanisms that link HHCY to both diseases.
      Existing data suggest that HHCY could be a useful paradigm with most interesting
      therapeutic implications, because HCY lowering therapy could favourably influence
      the course in CHF and osteoporotic patients.

PMID- 16584061
TI  - Investigations of ascorbic acid interference in urine test strips.
AB  - Ascorbic acid at higher concentration in urine samples can lead to false negative
      results in a number of urine tests, with a potential risk of clinical findings
      being overlooked, particularly with glucose and hemoglobin. For this reason, the
      ascorbic acid status of urine samples should always be routinely known so as to
      establish what adjustment needs to be made. A much better approach, however, is
      to use a test which is by design largely resistant to ascorbic acid. We compared
      five very common 10-parameter urine test strips from different manufacturers. The
      results of this study show that of the strips tested, only the product Combur
      Test from Roche Diagnostics is largely resistant to ascorbic acid interference.
      Even lowest - but clinically relevant - concentrations of erythrocytes
      (10/microL), hemoglobin (0.03 mg/dL), and glucose (50 mg/dL) were correctly
      detected with concentrations of up to 400 mg/L ascorbic acid. Higher analyte
      concentrations correctly reacted positive even in the presence of up to 1000 mg/L
      ascorbic acid.

PMID- 16584062
TI  - The inborn errors of sialic acid metabolism and their laboratory investigation.
AB  - Sialic acid (SA), a terminal monosaccharide of glycoconjugates, has a central
      role in human biological function. Various point mutations result in the
      malmetabolism of SA and inherited disorders: Defective SA synthesis causes
      sialuria and defective SA catabolism causes sialidosis and sialic acid storage
      disease (SASD). These inborn errors of metabolism are characterised by increased
      urinary free SA. This article reviews biochemical and clinical features that are
      distinct to each disorder. In view of recent evidence indicating a wide
      underestimation in the prevalence of sialic acid disorders, laboratory methods
      for determining urinary free SA and its implications for screening and prenatal
      diagnosis are evaluated.

PMID- 16584063
TI  - Sample size calculations based on generalized estimating equations for population
      pharmacokinetic experiments.
AB  - We present a method for calculating the sample size of a pharmacokinetic study
      analyzed using a mixed effects model within a hypothesis testing framework. A
      sample size calculation method for repeated measurement data analyzed using
      generalized estimating equations has been modified for nonlinear models. The Wald
      test is used for hypothesis testing of pharmacokinetic parameters. A marginal
      model for the population pharmacokinetic is obtained by linearizing the
      structural model around the subject specific random effects. The proposed method
      is general in that it allows unequal allocation of subjects to the groups and
      accounts for situations where different blood sampling schedules are required in
      different groups of patients. The proposed method has been assessed using Monte
      Carlo simulations under a range of scenarios. NONMEM was used for simulations and
      data analysis and the results showed good agreement.

PMID- 16584064
TI  - A ratio test in active control non-inferiority trials with a time-to-event
      endpoint.
AB  - There are essentially two kinds of non-inferiority hypotheses in an active
      control trial: fixed margin and ratio hypotheses. In a fixed margin hypothesis,
      the margin is a prespecified constant and the hypothesis is defined in terms of a
      single parameter that represents the effect of the active treatment relative to
      the control. The statistical inference for a fixed margin hypothesis is
      straightforward. The outstanding issue for a fixed margin non-inferiority
      hypothesis is how to select the margin, a task that may not be as simple as it
      appears. The selection of a fixed non-inferiority margin has been discussed in a
      few articles (Chi et al., 2003; Hung et al., 2003; Ng, 1993). In a ratio
      hypothesis, the control effect is also considered as an unknown parameter, and
      the noninferiority hypothesis is then formulated as a ratio in terms of these two
      parameters, the treatment effect and the control effect. This type of non
      inferiority hypothesis has also been called the fraction retention hypothesis
      because the ratio hypothesis can be interpreted as a retention of certain
      fraction of the control effect. Rothmann et al. (2003) formulated a ratio non
      inferiority hypothesis in terms of log hazards in the time-to-event setting. To
      circumvent the complexity of having to deal with a ratio test statistic, the
      ratio hypothesis was linearized to an equivalent hypothesis under the assumption
      that the control effect is positive. An associated test statistic for this
      linearized hypothesis was developed. However, there are three important issues
      that are not addressed by this method. First, the retention fraction being
      defined in terms of log hazard is difficult to interpret. Second, in order to
      linearize the ratio hypothesis, Rothmann's method has to assume that the true
      control effect is positive. Third, the test statistic is not powerful and thus
      requires a huge sample size, which renders the method impractical. In this paper,
      a ratio hypothesis is defined directly in terms of the hazard. A natural ratio
      test statistic can be defined and is shown to have the desired asymptotic
      normality. The demand on sample size is much reduced. In most commonly
      encountered situations, the sample size required is less than half of those
      needed by either the fixed margin approach or Rothmann's method.

PMID- 16584066
TI  - A new paradigm for deriving and analyzing number needed to treat.
AB  - The inverse of the risk difference, commonly referred to as the number needed to
      treat (NNT) has been recently proposed as a useful measure for comparing two
      treatments. Since its introduction, the method has been used widely to establish
      comparative treatment benefits, and has also been the subject of extensive
      discussions among statisticians. In this paper, we examine the assumptions behind
      the original definition of NNT, and introduce a new formulation of the method
      based on a random walk model. Using stopping times, we develop a paradigm for NNT
      that avoids some of the conceptual and inferential difficulties and pitfalls
      associated with the previous work on NNT. Simulation results are provided to
      illustrate the bias introduced by using alternative formulations of NNT, and
      several open problems are suggested for future research.

PMID- 16584065
TI  - Multiple polyexponentials and quasipolynomials as empirical nonlinear regression
      models: a case study with HIV viral load data.
AB  - Measurements of HIV1-RNA plasma concentrations are an important method of
      assessing patient response to anti-HIV1 treatment, and in most clinical trials of
      such treatments HIV1-RNA levels are assessed at regular intervals of time. HIV1
      RNA levels in successfully treated patients tend to follow a standard pattern of
      biphasic decline-a rapid early decline in viral load, followed by a period of
      slower decline or a steady level. Fitting nonlinear regression models to these
      patterns of declining HIV1-RNA levels can be of value in comparing different
      treatment regimes and in predicting treatment outcome. Simple exponential-decline
      models can give an adequate fit to the typical pattern of HIV1-RNA decline, but
      we have explored the extent to which curve-fitting can be improved by using two
      novel nonlinear model forms. Specifically, we describe the fitting of multiple
      polyexponential and quasipolynomial forms to longitudinal HIV1-RNA plasma data
      collected in two recent trials of the novel anti-HIV1 treatment Fuzeon. We
      comment on the practicalities of fitting these nonlinear models, and compare the
      fit using various criteria.

PMID- 16584067
TI  - Profile likelihood-based confidence intervals using Monte Carlo integration for
      population pharmacokinetic parameters.
AB  - Population pharmacokinetic (PPK) analysis usually employs nonlinear mixed effects
      models using first-order linearization methods. It is well known that
      linearization methods do not always perform well in actual situations. To avoid
      linearization, the Monte Carlo integration method has been proposed. Moreover, we
      generally utilize asymptotic confidence intervals for PPK parameters based on
      Fisher information. It is known that likelihood-based confidence intervals are
      more accurate than those from the usual asymptotic confidence intervals. We
      propose profile likelihood-based confidence intervals using Monte Carlo
      integration. We have evaluated the performance of the proposed method through a
      simulation study, and analyzed the erythropoietin concentration data set by the
      method.

PMID- 16584068
TI  - Average bioequivalence evaluation: general methods for pilot trials.
AB  - In clinical development of a bioequivalent (BE) drug product, a two-step strategy
      is commonly adopted. In the first step, a pilot BE trial is conducted to evaluate
      the acceptability of the test drug product as a candidate for further evaluation
      in a subsequent pivotal BE trial. In the second step, a full-scale pivotal BE
      trial is conducted to formally establish bioequivalence. The objective and
      criterion of a pilot BE trial are different from those of a pivotal BE trial. In
      practice, however, a pilot BE trial is often inappropriately designed and
      analyzed based on the criterion for a pivotal BE trial. One main reason is the
      lack of well-established design and analysis methods for a pilot BE trial. To
      close this gap in practice, this study proposes a Pilot Acceptance Range method
      specfically constructed for analyzing a pilot BE trial within the framework of a
      two-step strategy. For designing a crossover pilot BE trial, this paper derives
      the power function and provides an easy-to-use method for determining the sample
      size.

PMID- 16584069
TI  - Covariate-adjusted adaptive designs for continuous responses in a phase III
      clinical trial: recommendation for practice.
AB  - One adaptive design is proposed and studied by Bandyopadhyay and Biswas (2001)
      for comparing two treatments having continuous responses with covariates at hand
      in a phase III clinical trial. On the other hand, a drop-the-loser urn design is
      recently proposed by Ivanova (2003), which is known to have the least variability
      among urn-based adaptive designs for binary responses. The drop-the-loser rule
      for continuous data was recently introduced by Ivanova et al. (2005). But neither
      of the works considered covariates for the allocation design. The present paper
      provides a version of the newly proposed adaptive design, drop-the-loser rule,
      but for continuous responses and by incorporating the covariate information in
      the allocation procedure. Several exact and limiting properties of the design,
      and also of a simpler version of it, are studied. We compare the design of
      Bandyopadhyay and Biswas (2001) with the covariate-adjusted drop-the-loser-type
      rule for continuous responses and conclude that, although the drop-the-loser rule
      is better for binary responses, the design of Bandyopadhyay and Biswas (2001)
      performs better than the drop-the-loser-type rule for continuous responses with
      covariates. We recommend the existing design of Bandyopadhyay and Biswas (2001)
      for practical purposes.

PMID- 16584070
TI  - Simultaneous use of weighted logrank and standardized Kaplan-Meier statistics.
AB  - Rank-based test procedures in censored survival data differ considerably in their
      sensitivity to various alternatives to the hypothesis of equality of underlying
      distributions. Procedures based on the simultaneous use of multiple statistics
      provide an appealing approach to obtaining more global sensitivity while
      maintaining the sensitivity to alternatives of interest. In this article, the
      joint distribution of weighted logrank statistics (to assess overall differences
      in time-to-event distributions) and a standardized difference in Kaplan-Meier
      estimates (to assess differences at a specific prespecified time post
      randomization) is obtained and this result is used to formulate statistical test
      procedures based on the simultaneous use of these two types of statistics.
      Simulations are used to assess small sample properties of this approach and its
      usefulness is illustrated in important recent oncology clinical trials.

PMID- 16584071
TI  - A comparison of three families of survival distributions for quantal response
      data.
AB  - In clinical studies, it is common to search for a suitable distribution function
      to model the survival pattern of test subjects after a treatment is administered
      to them. Though many distributions have appeared in the statistical literature,
      this study explores a family of three-parameter distributions, namely, the
      exponentiated Weibull family, and compares its performance with the other two
      popular families. Results suggest that the three families show similar
      performance. Three data sets, which are published in the literature, are
      reanalysed for illustration purposes.

PMID- 16584072
TI  - Essentials of glycosylation.

PMID- 16584073
TI  - Metabolic mimics: the disorders of N-linked glycosylation.
AB  - N-linked glycosylation is essential for normal cellular function. Defects have
      now been described in eighteen genes that participate in the process. All give
      rise to complex multisystem diseases which, with a few exceptions, primarily
      involve the nervous system. Frequent features of these disorders include
      developmental delay, ataxia, seizures, stroke-like episodes, recurrent
      infections, coagulopathy and dysmorphism. Most cases can be detected by screening
      carbohydrate-deficient transferrin, but definitive diagnosis requires enzymatic
      and molecular confirmation, frequently in collaboration with a research
      glycobiologist.

PMID- 16584075
TI  - Methods for detection of carbohydrate-deficient glycoprotein syndromes.

PMID- 16584076
TI  - Customer satisfaction: are hospitals "hospitable"?

PMID- 16584074
TI  - The dystroglycanopathies: the new disorders of O-linked glycosylation.
AB  - It has become clear in the past half decade that a number of forms of congenital
      muscular dystrophy are in fact congenital disorders of glycosylation. Genes for
      Walker Warburg syndrome, muscle-eye-brain disease, Fukuyama congenital muscular
      dystrophy, congenital muscular dystrophy 1C and 1D, and limb girdle muscular
      dystrophy 21 have been identified, and gene mutations resulting in these diseases
      all cause the underglycosylation of alpha dystroglycan with O-linked
      carbohydrates. Unlike congenital disorders of glycosylation involving the N
      linked pathway, these O-linked disorders possess distinctive muscle, eye, and
      brain phenotypes. Studies using mice and patient tissues strongly suggest that
      underglycosylation of dystroglycan inhibits the binding extracellular matrix
      proteins, effectively divorcing this important cell adhesion molecule from its
      extracellular environment. Moreover, defects in dystroglycan alone can account
      for most, if not all, cellular pathology. Thus, these disorders are now
      collectively referred to as dystroglycanopathies.

PMID- 16584077
TI  - Musculoskeletal tumor biopsy: I. Choosing the appropriate method.

PMID- 16584078
TI  - A safe technique for sternoclavicular stabilization.
AB  - Sternoclavicular stabilization using metal implants is associated with an
      unacceptably high complication rate. A simple and safe technique of
      sternoclavicular stabilization utilizing sutures and the clinical results thereof
      are described in this case of an 11-year-old boy with an unstable anterior
      sternoclavicular dislocation.

PMID- 16584079
TI  - Orthopedic surgical management of hip and knee involvement in patients with
      juvenile rheumatoid arthritis.
AB  - Juvenile rheumatoid arthritis is the most common arthritic disease of childhood
      and a leading cause of childhood disability, affecting an estimated 300,000 US
      children and adolescents aged < or =16 years. Approximately 10% to 30% of
      patients experience functional deficits resulting from both the articular and
      systemic manifestations of their disease, including leg length inequality and
      deformity, that are often more crippling than joint destruction. Surgical
      intervention to treat bone and soft-tissue deformity, leg length inequality, and
      joint destruction is indicated when medical therapy has failed. Synovectomy, soft
      tissue release, osteotomy, and epiphysiodesis are used to treat deformity and
      early joint destruction. Arthroplasty remains the primary therapy for joint
      destruction, although it is fraught with complications specific to this young
      patient population.

PMID- 16584080
TI  - Predictive value of preoperative arterial blood gas evaluation for geriatric
      patients with hip fractures.
AB  - The high incidence of preoperative silent pulmonary embolisms (PEs) among elderly
      patients with hip fractures has led some authors to recommend making acquisition
      of arterial blood gas (ABG) levels a routine part of the preoperative workup. In
      the study reported here, we retrospectively reviewed 254 patients in our hip
      fracture database and determined that ABG levels have poor positive predictive
      value for PEs and add little to the positive predictive value or negative
      predictive value of careful clinical examination. Therefore, we do not recommend
      making acquisition of ABG levels a routine part of the preoperative evaluation.

PMID- 16584081
TI  - Effects of a cyclooxygenase-2 inhibitor (rofecoxib) on bone healing.
AB  - In the study reported here, we determined the effects on bone healing of
      rofecoxib, one of the selective cyclooxygenase-2 (Cox-2) inhibitors that has been
      used for postsurgical analgesia, and compared these effects with those of
      nonselective ibuprofen and placebo. Each of 66 male rats received a closed,
      nondisplaced femoral fracture and was fed rofecoxib, ibuprofen, or placebo for 4
      weeks. Results of postsacrifice evaluation showed gross nonunions in 64.7% of
      rofecoxib rats (P < .0001), 17.6% of ibuprofen rats (P = .007), and 0% of placebo
      rats. Compared with ibuprofen, rofecoxib was significantly more likely to produce
      nonunions (P = .007). Mean callus width was 8.9 mm (SD, 1.3 mm) for rofecoxib (P
      = .03), 8.9 mm (SD, 1.2 mm) for ibuprofen (P = .03), and 8.0 mm (SD, 1.3 mm) for
      placebo. Mean healing maturity (Goldberg classification) was 1.6 (SD, 0.7) for
      rofecoxib (P < .0001), 1.7 (SD, 0.8) for ibuprofen (P = .0001), and 2.7 (SD, 0.6)
      for placebo. Mean fracture angulation was 30.8 degrees (SD, 16.7 degrees) for
      rofecoxib (P = .003), 14.3 degrees (SD, 14.4 degrees) for ibuprofen (NS), and
      13.4 degrees (SD, 10.3 degrees) for placebo. Mean histologic healing was 5.75 for
      rofecoxib (P = .02), 6.35 for ibuprofen (P = .05), and 8.25 for placebo. Cox-2
      inhibitors should be used with caution when bone healing is necessary. Further
      study is warranted to determine whether the adverse effects occur in humans.

PMID- 16584082
TI  - Radial nerve entrapment secondary to a solitary nodular fasciitis mass in the
      forearm.

PMID- 16584083
TI  - Thumb metacarpal closing wedge osteotomy for diminished first web space following
      Weilby arthroplasty.

PMID- 16584084
TI  - The underestimation of a glass injury to the hand.
AB  - This study sought to ascertain the differences between what is found on an
      orthopedic preoperative examination of a glass injury to the hand and the actual
      intraoperative deficiencies noted in the operating room. The cases of 34 patients
      who presented to our institution for a shattered glass laceration to the hand,
      forearm, or wrist between 1998 and 2001 were reviewed. The preoperative
      examination significantly underestimated the amount of damage to tendons,
      arteries and nerves. The most frequent injury pattern was the flexor digitorum
      superficialis (34/103 = 33%), the radial artery (7/18 = 39%), and the superficial
      branch of the radial nerve (7/32 = 22%). A glass injury to the hand can be a
      deceivingly debilitating and significant injury. The preoperative examination,
      even when specifically evaluating for deficiencies, significantly underestimates
      the extent of damage. If glass is implicated as a causative agent, careful
      orthopedic evaluation and surgical management should be considered even in light
      of a normal preoperative examination.

PMID- 16584085
TI  - The role of nitric oxide in the hypothalamic control of LHRH and oxytocin
      release, sexual behavior and aging of the LHRH and oxytocin neurons.
AB  - Nitric oxide (NO) affects reproductive processes both at the level of the brain
      and reproductive tract and this review is focused on its role as an essential
      regulator of the hypothalamic control of reproduction. The data gathered indicate
      that glutamate stimulates noradrenergic neurons which subsequently activate NO
      ergic cells via alpha1-adrenergic receptors. The released NO diffuses into
      luteinizing hormone-releasing hormone (LHRH) terminals where it triggers LHRH
      secretion by activation of guanylyl cyclase and cyclooxygenase. The NO released
      by estrogen-stimulated NO-ergic ventromedial neurons plays a crucial role in the
      regulation of sexual behavior. Furthermore, an increased expression of inducible
      nitric oxide synthase in the LHRH and oxytocin neurons underlies the destructive
      action of NO on the aging of the hypothalamic neuroendocrine pathways. Within the
      hypothalamo-hypophyseal system, NO exerts an inhibitory effect in the control of
      oxytocin secretion. This action seems to employ an indirect mechanism by which NO
      may modulate the release of GABA. This review provides an overview of the role of
      NO in hypothalamic control of LHRH and oxytocin release, aging of the LHRH and
      oxytocin neurons and sexual behavior.

PMID- 16584086
TI  - Expression of NPY-immunoreactive neurons in the hypothalamus of the cycling ewe.
AB  - The purpose of the study was to localise neuropeptide Y (NPY) immunoreactive (ir)
      neurons in the hypothalamus during two phases of the oestrous cycle in the ewe.
      Hypothalamic tissue was collected from Polish Merino ewes (n=8) in the follicular
      (15th day) and preovulatory (17th day) phases of the oestrous cycle. NPY-ir
      neurons were detected in the hypothalamus using immuohistochemistry followed by
      image analysis; positive staining was expressed as the percentage of stained area
      and optical density. Two populations of the NPY-positive neurons were detected
      and evaluated in the infundibular and periventricular nuclei of the hypothalamus.
      The population of NPY-ir neurons located in the infundibular nucleus exhibited a
      prominent expression of NPY immunoreactivity in the perikarya and fibres only
      during the preovulatory phase. Both, percent area and the optical density of NPY
      immunostaining measured in this area were higher (P < 0.01) in the preovulatory
      than in the follicular phase. Another population of NPY-ir neurons was localised
      in the periventricular nucleus and did not show any changes during the two phases
      of the cycle. The present study suggests that NPY-ir neurons present in the
      infundibular nucleus can play a role in the preovulatory GnRH discharge from the
      median eminence.

PMID- 16584088
TI  - Morphology of the epithelial cells and expression of androgen receptor in rat
      prostate dorsal lobe in experimental hyperprolactinemia.
AB  - The effect of hyperprolactinemia on the prostate has not been well investigated.
      Since androgens play an important role in prostate development, growth and
      function, the goal of the present study was to estimate the influence of
      hyperprolactinemia on expression of the androgen receptor (AR) in rat epithelial
      cells of prostate dorsal lobe and on morphology of these cells. Studies were
      performed on sexually mature male Wistar rats. The experimental group rats
      received metoclopramide (MCP) intraperitoneally to provoke hyperprolactinemia.
      The control group animals were given saline in the same way. For light and
      electron microscopy the prostate dorsal lobes were obtained routinely. To
      evaluate the intensity of immunohistochemical reaction for AR in epithelial
      cells, the optical density was measured and computer-assisted image analysis
      system was used. Morphological observations of the dorsal lobe epithelial cells
      were carried out in transmission electron microscope. MCP caused over twofold
      increase in prolactin (PRL) serum levels. In rats with hyperprolactinemia, the
      testosterone levels (T) were twofold decreased. The intensity of
      immunohistochemical reaction for AR in epithelial cells of dorsal lobe in the
      experimental group was significantly lower than in the control group. In the
      dorsal lobe epithelial cells of experimental group animals, the transmission
      electron microscopy (TEM) revealed highly dilated RER cisternae and reduced
      number of microvilli on the cellular surface when compared to the control group.
      The results show that hyperprolactinemia in male rats causes morphological
      abnormalities in the dorsal lobe of prostate. The abnormalities are caused by
      elevated prolactin either directly or indirectly through decreased level of
      testosterone. Decreased expression of AR in epithelial cells of prostate dorsal
      lobe is likely to be caused by decreased testosterone level.

PMID- 16584087
TI  - VEGF, VEGFR-1 and VEGFR-2 immunoreactivity in the porcine arteries of vascular
      subovarian plexus (VSP) during the estrous cycle.
AB  - Abstract: Vascular endothelial growth factor (VEGF) is an important angiogenic
      factor in the female reproductive tract. It binds to cell surface through ligand
      stimulatable tyrosine kinase receptors, the most important being VEGFR-1 (flt-1)
      and VEGFR-2 (flk-1). The broad ligament of the uterus is a dynamic organ
      consisting of specialized complexes of blood vessels connected functionally to
      the uterus, oviduct and ovary. Endothelial cells form an inner coating of the
      vessel walls and thus they stay under the influence of various modulators
      circulating in blood including ovarian steriods involved in developmental changes
      in the female reproductive system. The aim of the present study was to
      immunolocalize VEGF and its two receptors: VEGFR-1 and VEGFR-2 in the broad
      ligament of the uterus in the area of vascular subovarian plexus during different
      phases of the estrous cycle in pig and to determine the correlation between
      immunoreactivity of the investigated factors and phases of the estrous cycle. The
      study was performed on cryostat sections of vascular subovarian plexus stained
      immunohistochemically by ABC method. Specific polyclonal antibodies: anti-VEGF,
      anti-VEGFR-1 and anti-VEGFR-2 were used. Data were subjected to one-way analysis
      of variance. Our study revealed the presence of VEGF and its receptors in
      endothelial and smooth muscle cells of VSP arteries. All agents displayed phase
      related differences in immunoreactivity suggesting the modulatory effect of VEGF,
      VEGFR-1 and VEGFR-2 on the arteries of the VSP in the porcine broad ligament of
      the uterus.

PMID- 16584089
TI  - Spontaneous apoptosis of melanotic and amelanotic melanoma cells in different
      phases of cell cycle: relation to tumor growth.
AB  - Since the spontaneous alteration of native melanotic (Ma) into amelanotic (Ab)
      transplantable melanoma line it has been observed that this alteration is
      accompanied by the acceleration of growth of Ab line. The aim of the present
      study was to check and estimate spontaneous apoptosis of cells from cell cycle
      phases. Cytometric cell cycle analysis was performed by staining cells with
      propidium iodide (PI). Apoptosis estimated by the TUNEL method, alterations in
      the plasma membrane structure (annexin V staining), changes in the mitochondrial
      transmembrane potential--delta psi m (JC-1 staining) showed that amelanotic
      melanoma cells have decreased ability to undergo spontaneous apoptosis. The
      obtained results showing that in the native melanotic line about 30% of cells are
      in S+G2/M phases and that 33% of these cells undergo apoptosis could lead to the
      conclusion that the slower growth of this melanoma line is the result of lower
      proliferation activity and higher rate of apoptosis of these tumor cells. The
      number of cells in S+G2/M phases in amelanotic melanoma line increases up to 40%
      and only 7% of them undergo apoptosis. This observation seems to suggest that the
      expansive growth of this melanoma line depends mainly on the decreased ability to
      undergo spontaneous apoptosis, especially in case of cells from S+G2/M phases.
      Moreover, the obtained results indicate that alteration of melanotic line into
      amelanotic one, accompanied by differences in many biological features also
      concerns basic cell processes such as cell cycle and cell death.

PMID- 16584090
TI  - Proliferating cell nuclear antigen (PCNA) expression in pituitary adenomas:
      relationship to the endocrine phenotype of adenoma.
AB  - The expression of proliferating cell nuclear antigen (PCNA) correlates to cell
      proliferation and for this reason it is commonly considered as one of
      proliferation markers. Since proliferation rate is an important factor
      determining the tumor aggressiveness, the evaluation of PCNA index (the
      percentage of PCNA-immunopositive nuclei in the investigated tumor sample) is
      suggested as useful in predicting pituitary adenoma outcome. Seventy three
      unselected, surgically removed pituitary adenomas were immunostained with
      antibodies against the pituitary hormones or their subunits and against the
      proliferating cell nuclear antigen (PCNA). The highest PCNA index was found in
      ACTH-immunopositive tumors without the manifestation of the Cushing's disease
      ("silent" corticotropinomas). This value was significantly different in
      comparison to other adenoma subtypes including corticotropinomas manifesting
      themselves by Cushing's disease. The lowest PCNA index was noticed in
      monohormonal GH-secreting tumors. The adenomas which express more than one
      hormone (plurihormonal adenomas) seem to have a higher PCNA indices than
      monohormonal ones; the difference was significant in the case of mono- and
      plurihormonal prolactinomas. The recurrent tumors presented a higher mean PCNA
      index as compared to the primary tumors, although the difference was significant
      only in the case of prolactinomas. These findings suggest that the proliferative
      potential of pituitary adenomas is related to the tumor recurrence and hormone
      expression.

PMID- 16584091
TI  - Density of intranodal lymphatics and VEGF-C expression in B-cell lymphoma and
      reactive lymph nodes.
AB  - Lymphatic vasculature in solid tumors may serve as the pathway for metastatic
      spread of the cancer to the regional lymph nodes and to distant organs.
      Controversy still exists whether tumors metastasize through existing lymphatics
      or through newly formed vessels (lymphangiogenesis). The role of
      lymphangiogenesis in lymphoma spread and proliferation is not clearly
      established. VEGF-C is the most potent inducer of lymphangiogenesis. LYVE-1 was
      shown to be a specific marker for lymphatic vessels in normal and tumor tissue.
      The aim of the present study was the evaluation of lymph node LYVE-1-positive
      lymphatic sinus density (LSD) and VEGF-C expression in patients with non
      Hodgkin's lymphoma (nHL) and in reactive lymph nodes. Sixty paraffin-embedded
      lymph nodes from newly diagnosed patients with B-cell nHL were evaluated. Twelve
      lymph node biopsy specimens from adult patients with reactive lymphonodulitis
      were used as controls. Sections of lymph nodes were stained immunohistochemically
      for LYVE-1 and VEGF-C. VEGF-C expression in lymph nodes of nHL patients was low
      and not significantly different from that in the control (p = 0.6). Moreover,
      VEGF-C expression did not differ significantly between aggressive and indolent
      lymphomas (p = 0.53). Similarly we did not find differences in LSD in aggressive
      nHL and in indolent nHL (p=0.49). The mean LSD in reactive lymph nodes was higher
      than in nHL (p = 0.03). Only in 2 out of 12 reactive lymph nodes LYVE-1-positive
      vessels were absent. In all groups we demonstrated a strong positive correlation
      between VEGF-C and LYVE-1-expression (p = 0.0001). Higher LSD in reactive lymph
      nodes as compared to those of nHL patients suggests that lymphoma proliferation
      leads to the destruction of the existing lymphatics rather than to
      lymphangiogenesis within lymph nodes. NHL are not associated with increased
      expression of VEGF-C nor increased LYVE-1-positive lymphatic sinuses density
      within lymph nodes.

PMID- 16584092
TI  - Prognostic significance of Ki67-negative blast cell clone in the high risk group
      of children treated for acute myeloid leukaemia.
AB  - The aim of this study was to demonstrate the value of immunocytochemical staining
      of Ki67 antigen expression in blast cells of children with acute myeloid leukemia
      (AML) and to evaluate its correlation with treatment failure. The material
      included bone marrow specimens obtained during induction treatment from 46
      children treated for AML between 1998-2003. Immunocytochemical staining for Ki67
      was based on the ABC technique. Expression of Ki67 antigen on day 0 of induction
      treatment was confirmed in all patients. The percentage of immunopositive blasts
      ranged from 88.4% to 99.8% (mean 91.8%). On day 15, according to chemotherapy
      response, patients were divided into two groups: G1-36 children who responded to
      induction treatment and reached remission (blast level 5%, low risk group) and G2
      10 patients who did not meet remission criterion (blast level > 5%) and were
      assigned to the high risk (HR) group. Out of 10 children assigned to this group,
      Ki67 expression in blast cells was confirmed in 4 cases. The fraction of
      immunopositive blasts ranged from 78.4% to 88.6%. In the other 6 cases, blasts
      were Ki67-negative. In 12-month period after beginning the treatment, 18 cases of
      treatment failure (including 7 deceases) were observed in both groups. Five
      deaths, observed in the HR group, concerned the patients characterized by Ki67
      negative blasts. The results indicate a possible correlation between the Ki67
      immunonegative blast pattern on day 15 of treatment induction and early decease
      of AML children assigned to HR group.

PMID- 16584093
TI  - Flow cytometric enumeration of CD34+ hematopoietic stem and progenitor cells in
      leukapheresis product and bone marrow for clinical transplantation: a comparison
      of three methods.
AB  - Flow cytometric enumeration of CD34+ hematopoietic stem and progenitor cells
      (HSCs) is widely used for evaluation of graft adequacy of peripheral blood and
      bone marrow stem cell grafts. In the present study, we review and compare the
      major counting techniques of stem and progenitor cells. The methods are: the
      Milan/Mullhouse protocol, two-platform ISHAGE (International Society of
      Hematotherapy and Graft Engineering) and single-platform ISHAGE analysis system.
      According to the Milan/Mulhouse protocol, HSCs are identified by CD34 antibody
      staining and easy gating strategy. The ISHAGE guidelines for detection of CD34+
      cells are based on a four-parameter flow cytometry method (CD34PE/CD45PerCP
      staining, side and forward angle light scatter) thus employing multiparameter
      gating strategy. With two-platform ISHAGE protocol, an absolute CD34+ count is
      generated by incorporating the leukocyte count from an automated hematology
      analyser. The single-platform ISHAGE method to determine the absolute CD34+ count
      directly from a flow cytometer includes the use of Trucount tubes (Becton
      Dickinson) with a known number of fluorescent beads. CD34+ cells were quantified
      in mobilized peripheral blood, collected by leukapheresis, and bone marrow from
      42 samples from patients with hematological malignancies. The differences against
      the means display low disagreement between the Milan/Mulhouse and ISHAGE
      protocols, with discrepancies of up to 2.5% (two-platform ISHAGE)--2.6% (single
      platform ISHAGE) in enumeration of CD34+ cells in leukapheresis product and 4.8%
      (two-platform ISHAGE)--4.9% (single-platform ISHAGE) in bone marrow. Our results
      show high correlation among all three methods. Since the three protocols are
      compatible, choosing the most convenient in terms of costs, simplicity and
      compliance with clinical results appears to be a logical consequence.

PMID- 16584094
TI  - The number and distribution of blood dendritic cells in the epidermis and dermis
      of healthy human subjects.
AB  - Human blood dendritic cells (BDC) can be divided into three subsets: plasmacytoid
      DC (PDC) and two myeloid subsets--MDC1 and MDC2. Several studies revealed the
      presence of both MDC and PDC in blood of healthy subjects, however no precise
      literature data exist on the number and distribution of BDC in the skin. The aim
      of our study was to assess the number and distribution of BDC and their subtypes
      in the healthy skin. The-study included 30 healthy volunteers (age 18-51). Punch
      biopsies were taken from the buttock skin from each subject, and
      immunofluorescent staining was performed using monoclonal mouse IgG1 antibodies
      directed against BDCA-1, BDCA-2, BDCA-3 and BDC-4. The BDC were present both in
      the epidermis and dermis. PDC were detected mainly in the dermis (mean 1.2 cells
      per field). Myeloid subtypes were observed mainly in the middle layers of the
      epidermis and in the upper part of the dermis (mean 1.8 cells per field). The
      detection of blood dendritic cells in the skin proves their role in immune
      cutaneous surveillance.

PMID- 16584095
TI  - Autofluorescence in eleocytes of some earthworm species.
AB  - Immunocompetent cells of earthworms, coelomocytes, comprise adherent amoebocytes
      and granular eleocytes (chloragocytes). Both cell populations can be expelled via
      dorsal pores of adult earthworms by exposure to an electric current (4.5 V) for 1
      min. Analysis by phase contrast/fluorescence microscopy and flow cytometry
      demonstrated that eleocyte population of several species exhibits a strong
      autofluorescence. A high percentage (11-35%) of autofluorescent eleocytes was
      recorded in Allolobophora chlorotica, Dendrodrilus rubidus, Eisenia fetida, and
      Octolasion sp. (O. cyaneum, O. tyrtaeum tyrtaeum and O. tyrtaeum lacteum). In
      contrast, autofluorescent coelomocytes were exceptionally scarce (less than 1%)
      in representative Aporrectodea sp. (A. caliginosa and A. longa) and Lumbricus sp.
      (L. castaneus, L. festivus, L. rubellus, L. terrestris). Thus, this paper for the
      first time describes profound intrinsic fluorescence of eleocytes in some--but
      not all--earthworm species. The function (if any) and inter-species differences
      of the autofluorescent coelomocytes still remain elusive.

PMID- 16584096
TI  - Recent advances in depression. Where are we going?

PMID- 16584097
TI  - Depression: major problem for public health.
AB  - The aim of this Editorial is to discuss depression as an important disorder for
      public health. The literature regarding epidemiology, consequences, adequacy of
      service delivery and prevention of depression is reviewed. Depression is a common
      disorder with high lifetime rates, particularly in women, and those experiencing
      social adversity. It is a major cause of disability, and causes death both by
      suicide and due to raised rates of physical disorders. Many cases are undiagnosed
      and treatment is often inadequate. Primary prevention is not yet easily feasible
      but secondary prevention by earlier recognition, public and professional
      education, can produce benefits. There is a need for public health programmes
      aimed at improving recognition, treatment, and reducing consequences.

PMID- 16584098
TI  - The "NICE Guideline" on the treatment of depression.
AB  - The National Institute of Clinical Excellence (NICE) in the UK is responsible for
      producing evidence based guidelines for the treatment of most common illnesses,
      both physical and psychological. NICE uses a hierarchy of evidence, ranging from
      data from meta-analyses of randomised controlled trials (RCT's) at the apex, to
      the opinions of acknowledged experts at the bottom. The task of preparing
      guideline for depression involved us in performing clean meta-analyses of around
      8,000 published RCTs of the treatment of this disorder. Where drug treatments
      were concerned we used three indicators of efficacy, as well as considering
      toxicity, tolerability and cost. We also distinguished between studies carried
      out in primary care, and studies in patients treated by the mental health
      services. We found it helpful to arrange our report in terms of a "stepped care"
      model, addressing the indications for patients being referred on for more
      specialised, and expensive, treatments. In the full guideline we included our
      doubts that depression was a homogenous clinical entity, and our awareness of the
      limitations of relying on randomised controlled trials (RCT's) as the only source
      of evidence. This Editorial summarises the content of the guideline on the
      treatment of depression and discusses how it was received and also what it did
      not say.

PMID- 16584099
TI  - Recent advances in depression across the generations.
AB  - This Editorial presents recent research on the transmission of depression across
      three generations and discusses the implications for improving detection,
      treatment and prevention and for identifying important subgroups for biological
      studies. It reports a case-control study of three generations at high or low risk
      for major depression. The first two generations were followed longitudinally for
      20 years and were assessed blind to the clinical status of the other generations.
      Depression is highly familial across three generations. Over 60% of grandchildren
      (average age 12 yrs.) with two generations affected with depression already have
      some psychopathology. Anxiety disorders are usually the first presentation before
      puberty with an increase in depression in adolescents, especially among girls.
      New opportunities for early detection and treatment exist. Families with three
      generations affected with depression present a potentially important group for
      biological, genetic and neuroimaging studies.

PMID- 16584101
TI  - Looking for adolescents' well-being: self-efficacy beliefs as determinants of
      positive thinking and happiness.
AB  - AIMS: The present study is part of a longitudinal project aimed at identifying
      the personal characteristics and the developmental pathways conducive to
      successful adaptation from childhood to adulthood. The study examined the
      concurrent and longitudinal impact of self-efficacy beliefs on subjective well
      being in adolescence, namely positive thinking and happiness. Positive thinking
      has been operationalized as the latent dimension underlying life satisfaction,
      self-esteem and optimism. Happiness has been operationalized as the difference
      between positive and negative affects, as they are experienced in a variety of
      daily situations. METHODS: In a group of 664 Italian adolescents, a structural
      model positing adolescents' emotional and interpersonal self-efficacy beliefs as
      proximal and distal determinants of positive thinking and happiness has been
      tested. RESULTS: Findings attest to the impact of affective and interpersonal
      social self-efficacy beliefs on positive thinking and happiness both concurrently
      and longitudinally. CONCLUSIONS: Adolescents' self-efficacy beliefs to manage
      positive and negative emotions and interpersonal relationships contribute to
      promote positive expectations about the future, to mantain a high self-concept,
      to perceive a sense of satisfaction for the life and to experience more positive
      emotions.

PMID- 16584100
TI  - Prenatal cocaine exposure: an examination of childhood externalizing and
      internalizing behavior problems at age 7 years.
AB  - AIM: This study examines the relationship between prenatal cocaine exposure and
      parent-reported child behavior problems at age 7 years. METHODS: Data are from
      407 African-American children (210 cocaine-exposed, 197 non-cocaine-exposed)
      enrolled prospectively at birth in a longitudinal study on the neurodevelopmental
      consequences of in utero exposure to cocaine. Prenatal cocaine exposure was
      assessed at delivery through maternal self-report and bioassays (maternal and
      infant urine and infant meconium). The Achenbach Child Behavior Checklist (CBCL),
      a measure of childhood externalizing and internalizing behavior problems, was
      completed by the child's current primary caregiver during an assessment visit
      scheduled when the child was seven years old. RESULTS: Structural equation and
      GLM/GEE models disclosed no association linking prenatal cocaine exposure status
      or level of cocaine exposure to child behavior (CBCL Externalizing and
      Internalizing scores or the eight CBCL subscale scores). CONCLUSIONS: This
      evidence, based on standardized ratings by the current primary caregiver, fails
      to support hypothesized cocaine-associated behavioral problems in school-aged
      children with in utero cocaine exposure. A next step in this line of research is
      to secure standardized ratings from other informants (e.g., teachers, youth self
      report).

PMID- 16584102
TI  - [Randomised controlled trial of a behavioural family intervention: 1 year and 11
      years follow-up].
AB  - AIM: To test the efficacy of a Behavioural Family Therapy (BFT) in a routine
      setting, both short and long term, of a community mental health service (CMHS).
      METHODS: In a randomised clinical trial 24 patients with a diagnosis of
      schizophrenia, as confirmed by PSE-IX, were assigned to the BFT according to
      Falloon (n = 12) or to individual usual treatment (n = 12). They were assessed
      before and at the end of the active treatment (after one year), and after an 11
      years follow-up with compared on basic indicators (hospitalisations, length of
      stay, drop-out rate) and standardised instruments of psychopathological symptoms,
      social functioning, family burden. RESULTS: At one-year follow-up clinical
      important and statistically significant differences were observed for psychotic
      positive symptoms (p<0.01), self-care (p<0.01), autonomy in daily life (p<0.001),
      subjective/objective family burden (p<0.001). Other psychosocial variables showed
      positive outcomes non reaching statistical significance. At the 11-year follow
      up, marked differences were observed only in hospitalisations and drop-outs.
      CONCLUSIONS: The BFT was rather easy to implement in a CMHS and very cost
      effective. However, as it has been shown in other studies, to keep all the
      benefits a consistent program of monitoring with booster sessions is essential.

PMID- 16584103
TI  - [Primary headache in Italian early adolescents: correlation with stress and
      school social support].
AB  - AIMS: The aims of the study are to evaluate the prevalence rates for headache
      among an Italian sample of early-adolescents and the role of possible related
      factors (school stress and social support). METHODS: The survey reported here is
      part of the larger Health Behaviour in School Aged Children (HBSC) trans-national
      study, which is co-ordinated by the European Office of the World Health
      Organization. The data were gathered through self-administered questionnaires
      filled out by a representative sample of 4,386 (48.4% males) Italian students (11
      , 13- and 15-year old). The main areas covered in the questionnaire were health
      and health behaviour. RESULTS: The overall prevalence of frequent headache (at
      least once a week) was 40.5%. Boys are less at risk than girls and the prevalence
      increases with age. Moreover, school demands (positively) and teacher's support
      (negatively) showed a significant association with the outcome. CONCLUSIONS:
      Compared to other countries, results revealed how this symptom is very common
      among Italian's early adolescents. Further, results shows the relevance of the
      school setting, in terms of teacher's demands and support, for the prevention of
      this symptom among early adolescents.

PMID- 16584104
TI  - [Antidepressant and antipsychotic drug prescribing in Lombardy].
AB  - BACKGROUND: The patterns of antidepressant and antipsychotic drug prescribing
      have rarely been studied in large and geographically defined catchment areas. In
      the present study we examined the prevalence and distribution of antidepressant
      and antipsychotic prescribing in Lombardy, a northern Italy region of nine
      million inhabitants. METHODS: This study used the Regional Administrative
      Database of Lombardy. This database includes all prescriptions reimbursed by the
      National Health System in the population living in this region. All
      antidepressant and antipsychotic prescriptions dispensed from the 1st January to
      the 31st December 2001 were extracted and prevalence data calculated by dividing
      antidepressant and antipsychotic users by the total number of male and female
      residents in each age group. In addition, from the Regional database of hospital
      admissions we extracted all patients aged 65 or above with cerebrovascular
      related outcomes for the year 2002. The two databases were linked anonymously
      with the aim of investigating the relationship between exposure to psychotropics
      and occurrence of cerebrovascular accidents in the elderly. RESULTS: During the
      study period 404,238 individuals were dispensed antidepressants, yielding a
      prevalence of use of 2.85 (95% CI 2.84, 2.87) per 100 males and 5.92 (95% CI
      5.90, 5.94) per 100 females. The prevalence of use progressively rose with age in
      both sexes, with the highest rates in old and very old individuals. The majority
      of individuals received a pharmacological treatment with selective-serotonin
      reuptake inhibitors only, slightly more than 12% received a treatment with
      tricyclic antidepressants. A total of 86,187 subjects were dispensed
      antipsychotic agents, yielding a prevalence of use of 0.87 (95% CI 0.86, 0.88)
      per 100 males and 1.01 (95% CI 1.00, 1.02) per 100 females. The prevalence of use
      progressively rose with age in both sexes, with the highest rates in old and very
      old subjects. Concerning the relationship between exposure to second-generation
      antipsychotics (SGAs) and occurrence of cerebrovascular (CBV) accidents, the
      analysis showed a significantly increased risk of CBV events in elderly subjects
      exposed to SGAs in comparison with those exposed to first-generation
      antipsychotics (FGAs) (3,31%, 95% CI 2,95-3,69 vs. 2,37%, 95% CI 2,19-2,57).
      Finally the analysis indicated no differences in the proportion of
      cerebrovascular events in elderly subjects exposed to TCAs and SSRIs.
      CONCLUSIONS: The very high rates of antidepressant and antipsychotic drug
      prescribing detected in late life suggest the need of characterising these
      individuals in terms of medical and psychiatric characteristics, needs and
      quality of life. It also suggests the need for pragmatic clinical trials, carried
      out in the general practice, with the aim of assessing whether antidepressants
      are effective in these conditions. The data provide preliminary epidemiological
      evidence that exposure to SGAs, in comparison with exposure to FGAs,
      significantly increased the risk of cerebrovascular accidents in the elderly.

PMID- 16584105
TI  - [Multifamily psychoeducational intervention (MPI) for obsessive-compulsive
      disorder: a pilot study].

PMID- 16584106
TI  - [Admissions to five general hospital psychiatric wards in Naples, Italy].

PMID- 16584107
TI  - Wal-Mart rolls out its own health-care reform.

PMID- 16584108
TI  - Identification of HIV-1 epitopes that induce the synthesis of a R5 HIV-1
      suppression factor by human CD4+ T cells isolated from HIV-1 immunized hu-PBL
      SCID mice.
AB  - We have previously reported that immunization of the severe combined
      immunodeficiency (SCID) mice reconstituted with human peripheral blood
      mononuclear cells (PBMC) (hu-PBL-SCID mice) with inactivated human
      immunodeficiency virus type-1 (HIV-1)-pulsed-autologous dendritic cells (HIV-DC)
      elicits HIV-1-reactive CD4(+) T cells that produce an as yet to be defined novel
      soluble factor in vitro with anti-viral properties against CCR5 tropic (R5) HIV-1
      infection. These findings led us to perform studies designed to identify the
      lineage of the cell that synthesizes such a factor in vivo and define the
      epitopes of HIV-1 protein that have specificity for the induction of such anti
      viral factor. Results of our studies show that this property is a function of
      CD4(+) but not CD8(+) T cells. Human CD4(+) T cells were thus recovered from the
      HIV-DC-immunized hu-PBL-SCID mice and were re-stimulated in vitro by co-culture
      for 2 days with autologous adherent PBMC as antigen presenting cells, APC
      previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1
      reactive CD4(+) T cells. Aliquots of these re-stimulated CD4(+) T cells were then
      co-cultured with similar APC's that were previously pulsed with 10 microg/ml of a
      panel of HIV peptides for an additional 2 days, and their culture supernatants
      were examined for the production of both the R5 HIV-1 suppression factor and IFN
      gamma. The data presented herein show that the HIV-1 primed CD4(+) T cells
      produced the R5 suppression factor in response to a wide variety of HIV-1 gag,
      env, pol, nef or vif peptides, depending on the donor of the CD4(+) T cells.
      Simultaneous production of human interferon (IFN)-gamma was observed in some
      cases. These results indicate that human CD4(+) T cells in PBMC of HIV-1 naive
      donors have a wide variety of HIV-1 epitope-specific CD4(+) T cell precursors
      that are capable of producing the R5 HIV-1 suppression factor upon DC-based
      vaccination with whole inactivated HIV-1.

PMID- 16584109
TI  - Transfusion related acute lung injury (TRALI) caused by red blood cell
      transfusion involving residual plasma anti-HLA antibodies: a report on two cases
      and general considerations.
AB  - TRALI is considered a serious hazard among immune complications of blood
      transfusion and its occurrence is admitted to be globally underestimated. Each
      type of blood product is likely to cause TRALI. We report here on two consecutive
      observations of TRALI caused by red blood cell concentrates, in which anti-HLA
      class I and class II antibodies resulting from post-gravitational allo
      immunization were evidenced in donors. HLA class I and II antigenic community
      between recipients and donors' husbands were found and strong reacting IgG
      antibodies directed at several of those common antigens were detected in the
      donors' serum. Both donors had more than 3 pregnancies, raising the issue of
      blood donor selection or of plasma reduction for cellular products.

PMID- 16584110
TI  - Alterations in mesenteric lymph node T cell phenotype and cytokine secretion are
      associated with changes in thymocyte phenotype after LP-BM5 retrovirus infection.
AB  - In this study, mouse MLN cells and thymocytes from advanced stages of LP-BM5
      retrovirus infection were studied. A decrease in the percentage of IL-7(+) cells
      and an increase in the percentage of IL-16(+) cells in the MLN indicated that
      secretion of these cytokines was also altered after LP-BM5 infection. The
      percentage of MLN T cells expressing IL-7 receptors was significantly reduced,
      while the percentage of MLN T cells expressing TNFR-p75 and of B cells expressing
      TNFR-p55 increased. Simultaneous analysis of surface markers and cytokine
      secretion was done in an attempt to understand whether the deregulation of IFN
      gamma secretion could be ascribed to a defined cell phenotype, concluding that
      all T cell subsets studied increased IFN-gamma secretion after retrovirus
      infection. Finally, thymocyte phenotype was further analyzed trying to correlate
      changes in thymocyte phenotype with MLN cell phenotype. The results indicated
      that the increase in single positive either CD4(+)CD8(-) or CD4(-)CD8(+) cells
      was due to accumulation of both immature (CD3(-)) and mature (CD3(+)) single
      positive thymocytes. Moreover, single positive mature thymocytes presented a
      phenotype similar to the phenotype previously seen on MLN T cells. In summary, we
      can conclude that LP-BM5 uses the immune system to reach the thymus where it
      interferes with the generation of functionally mature T cells, favoring the
      development of T cells with an abnormal phenotype. These new T cells are
      activated to secrete several cytokines that in turn will favor retrovirus
      replication and inhibit any attempt of the immune system to control infection.

PMID- 16584111
TI  - SNP analysis of genes implicated in T cell proliferation in primary biliary
      cirrhosis.
AB  - Previous studies on primary biliary cirrhosis (PBC) have focused on the role of T
      lymphocytes as potential effectors of tissue injury. We hypothesized that single
      nucleotide polymorphisms (SNPs) of genes involved in lymphocyte proliferation
      would be responsible for uncontrolled expansion of T cells and autoreactivity. To
      address this, we genotyped DNA from 154 patients with PBC and 166 ethnically
      matched healthy controls for SNPs of five candidate genes (60G/A CTLA-4, 1858 C/T
      LYP, -IVS9 C/T foxp3, p1323 C/G ICOS and -9606 T/C CD25) using a TaqMan assay. We
      report herein a statistically significant decrease in homozygosity rate for the
      60A*CTLA-4 allele in patients with PBC compared to controls (p = 0.0411).
      Moreover, we found a significant association of the same allele and of the LYP*T
      allele with anti-mitochondrial antibody (AMA) serum negativity (p = 0.0304 and
      0.0094, respectively). No association between any of the other studied SNPs and
      PBC susceptibility, progression, or AMA status was observed. In conclusion, given
      the high prevalence of SNPs in CTLA-4 detected in numerous autoimmune diseases,
      we encourage a more detailed genetic analysis of this candidate gene. Further,
      although obtained from a limited number of AMA-negative subjects, our data
      suggest a potential genetic heterogeneity for this specific subgroup of patients
      with PBC.

PMID- 16584112
TI  - Inhibition of progenitor dendritic cell maturation by plasma from patients with
      peripartum cardiomyopathy: role in pregnancy-associated heart disease.
AB  - Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on
      their functional maturity, and both innate and adaptive immune responses have
      been implicated in myocardial tissue remodeling associated with cardiomyopathies.
      Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within
      one month antepartum to five months postpartum. A high occurrence of PPCM in
      central Haiti (1 in 300 live births) provided the unique opportunity to study the
      relationship of immune activation and DC maturation to the etiology of this
      disorder. Plasma samples from two groups (n = 12) of age- and parity-matched
      Haitian women with or without evidence of PPCM were tested for levels of
      biomarkers of cardiac tissue remodeling and immune activation. Significantly
      elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of
      TGF-beta were measured in PPCM subjects relative to controls. Yet despite these
      findings, in vitro maturation of normal human cord blood derived progenitor
      dendritic cells (CBDCs) was significantly reduced (p < 0.001) in the presence of
      plasma from PPCM patients relative to plasma from post-partum control subjects as
      determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability
      of these matured CBDCs to induce allo-responses in PBMCs. These results represent
      the first findings linking inhibition of DC maturation to the dysregulation of
      normal physiologic cardiac tissue remodeling during pregnancy and the
      pathogenesis of PPCM.

PMID- 16584113
TI  - Polymorphism of the fractalkine receptor CX3CR1 and systemic sclerosis-associated
      pulmonary arterial hypertension.
AB  - Fractalkine (FKN) and its receptor CX3CR1 are critical mediators in the vascular
      and tissue damage of several chronic diseases, including systemic sclerosis (SSc)
      and pulmonary arterial hypertension (PAH). Interestingly, the V249I and T280M
      genetic polymorphisms influence CX3CR1 expression and function. We investigated
      whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1
      genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and
      204 healthy controls. PAH was defined by colorDoppler echocardiography.
      Homozygosity for 249II as well as the combined presence of 249II and 280MM were
      significantly more frequent in patients with SSc compared to controls (17 vs 6%,
      p = 0.0034 and 5 vs 1%, p = 0.0027, respectively). The 249I and 280M alleles were
      associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75,
      p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively). In
      conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a
      subgroup of patients with SSc-associated PAH suggest a role for the fractalkine
      system in the pathogenesis of this condition. Further, the 249I allele might be
      associated with susceptibility to SSc.

PMID- 16584114
TI  - Why do people die of anaphylaxis? A clinical review.
AB  - Anaphylaxis is a source of anxiety for patients and healthcare providers. It is a
      medical emergency that presents with a broad array of symptoms and signs, many of
      which can be deceptively similar to other diseases such as myocardial infarction,
      asthma, or panic attacks. In addition to these diagnostic challenges, anaphylaxis
      presents management difficulties due to rapid onset and progression, lack of
      appropriate self-treatment education and implementation by patients, severity of
      the allergic response, exacerbating medications or concurrent disease, and
      unpredictability. The most common causes of anaphylaxis are food allergies,
      stinging insects and immunotherapy (allergy shots) but idiopathic anaphylaxis,
      latex allergy and drug hypersensitive all contribute to the epidemiology.
      Reactions to IVP and other dyes are coined anaphylactoid reactions but have
      identical pathophysiology and treatment, once the mast cell has been
      degranulated. As many antigens can be the trigger for fatal anaphylaxis, it is
      useful to examine the features of each etiology individually, highlighting
      factors common to all fatal anaphylaxis and some specific to certain etiologies.
      Generally what distinguishes a fatal from non fatal reaction is often just the
      rapidity to apply correct therapy. Prevention is clearly the key and should
      identify high-risk patients in an attempt to minimize the likely of a severe
      reaction. Although fatal anaphylaxis is rare, it is likely underreported.

PMID- 16584116
TI  - Cytochrome P450s and other enzymes in drug metabolism and toxicity.
AB  - The cytochrome P450 (P450) enzymes are the major catalysts involved in the
      metabolism of drugs. Bioavailability and toxicity are 2 of the most common
      barriers in drug development today, and P450 and the conjugation enzymes can
      influence these effects. The toxicity of drugs can be considered in 5 contexts:
      on-target toxicity, hypersensitivity and immunological reactions, off-target
      pharmacology, bioactivation to reactive intermediates, and idiosyncratic drug
      reactions. The chemistry of bioactivation is reasonably well understood, but the
      mechanisms underlying biological responses are not. In the article we consider
      what fraction of drug toxicity actually involves metabolism, and we examine how
      species and human interindividual variations affect pharmacokinetics and
      toxicity.

PMID- 16584115
TI  - Current industrial practices of assessing permeability and P-glycoprotein
      interaction.
AB  - Combination of the in vitro models that are high throughput but less predictive
      and the in vivo models that are low throughput but more predictive is used
      effectively to evaluate the intestinal permeability and transport characteristics
      of a large number of drug candidates during lead selection and lead optimization
      processes. Parallel artificial membrane permeability assay and Caco-2 cells are
      the most frequently used in vitro models to assess intestinal permeability. The
      popularity of these models stems from their potential for high throughput, cost
      effectiveness, and adequate predictability of absorption potential in humans.
      However, several caveats associated with these models (eg, poor predictability
      for transporter-mediated and paracellularly absorbed compounds, significant
      nonspecific binding to cells/devices leading to poor recovery, variability
      associated with experimental factors) need to be considered carefully to realize
      their full potential. P-glycoprotein, among other pharmaceutically relevant
      transporters, has been well demonstrated to be the major determinant of drug
      disposition. The review article presents an objective analysis of the
      permeability and transporter models currently being used in the pharmaceutical
      industry and could help guide the discovery scientists in implementing these
      models in an optimal fashion.

PMID- 16584117
TI  - Activation of G-proteins in brain by endogenous and exogenous cannabinoids.
AB  - The biological response to cannabinoid agonist begins when the agonist-bound
      receptor activates G-protein G(alpha) subunits, thus initiating a cascade of
      signal transduction pathways. For this reason, information about cannabinoid
      receptors/G-protein coupling is critical to understand both the acute and chronic
      actions of cannabinoids. This review focuses on these mechanisms, predominantly
      examining the ability of cannabinoid agonists to activate G-proteins in brain
      with agonist-stimulated [(35)S]guanylyl-5'-O-(gamma-thio)-triphosphate
      ([(35)S]GTPgammaS) binding. Acute efficacies of cannabinoid agonists at the level
      of G-protein activation depend not only on the ability of the agonist to induce a
      high affinity state in G(alpha) for GTP, but also to induce a low affinity for
      GDP. When several agonists are compared, it is clear that cannabinoid agonists
      differ considerably in their efficacy. Both WIN 55212-2 and levonantradol are
      full agonists, while Delta(9)-tetrahydrocannabinol is a weak partial agonist. Of
      interest, anandamide and its stable analog methanandamide are partial agonists.
      Chronic treatment in vivo with cannabinoids produces significant tolerance to the
      physiological and behavioral effects of these drugs, and several studies have
      shown that this is accompanied by a significant loss in the ability of
      cannabinoid receptors to couple to G-proteins in brain. These effects vary across
      different brain regions and are usually (but not always) accompanied by loss of
      cannabinoid receptor binding. Although the relationship between cannabinoid
      receptor desensitization and tolerance has not yet been established, these
      mechanisms may represent events that lead to a loss of cannabinoid agonist
      response and development of tolerance.

PMID- 16584119
TI  - Molecular recognition of opioid receptor ligands.
AB  - The cloning of the opioid receptors and subsequent use of recombinant DNA
      technology have led to many new insights into ligand binding. Instead of focusing
      on the structural features that lead to increased affinity and selectivity,
      researchers are now able to focus on why these features are important. Site
      directed mutagenesis and chimeric data have often been at the forefront in
      answering these questions. Herein, we survey pharmacophores of several opioid
      ligands in an effort to understand the structural requirements for ligand binding
      and selectivity. Models are presented and compared to illustrate key sites of
      recognition for both opiate and nonopiate ligands. The results indicate that
      different ligand classes may recognize different sites within the receptor,
      suggesting that multiple epitopes may exist for ligand binding and selectivity.

PMID- 16584120
TI  - Receptors of mammalian trace amines.
AB  - The discovery of a family of G-protein coupled receptors, some of which bind and
      are activated by biogenic trace amines, has prompted speculation as to the
      physiological role of these receptors. Observations associated with the
      distribution of these trace amine associated receptors (TAARs) suggest that they
      may be involved in depression, attention-deficit hyperactivity disorder, eating
      disorders, migraine headaches, and Parkinson's disease. Preliminary in vitro
      data, obtained using cloned receptors, also suggest a role for TAARs in the
      function of hallucinogens.

PMID- 16584118
TI  - Opioid ligands with mixed mu/delta opioid receptor interactions: an emerging
      approach to novel analgesics.
AB  - Opioids are widely used in the treatment of severe pain. The clinical use of the
      opioids is limited by serious side effects such as respiratory depression,
      constipation, development of tolerance, and physical dependence and addiction
      liabilities. Most of the currently available opioid analgesics exert their
      analgesic and adverse effects primarily through the opioid mu receptors. A large
      number of biochemical and pharmacological studies and studies using genetically
      modified animals have provided convincing evidence regarding the existence of
      modulatory interactions between opioid mu and delta receptors. Several studies
      indicate that delta receptor agonists as well as delta receptor antagonists can
      provide beneficial modulation to the pharmacological effects of mu agonists. For
      example, delta agonists can enhance the analgesic potency and efficacy of mu
      agonists, and delta antagonists can prevent or diminish the development of
      tolerance and physical dependence by mu agonists. On the basis of these
      observations, the development of new opioid ligands possessing mixed mu
      agonist/delta agonist profile and mixed mu agonist/delta antagonist profile has
      emerged as a promising new approach to analgesic drug development. A brief
      overview of mu-delta interactions and recent developments in identification of
      ligands possessing mixed mu agonist/delta agonist and mu agonist/delta antagonist
      activities is provided in this report.

PMID- 16584121
TI  - The pharmacokinetics of escitalopram in patients with hepatic impairment.
AB  - The effect of hepatic impairment on the pharmacokinetics of escitalopram was
      determined by means of nonlinear mixed effect modeling, considering both the
      Child-Pugh classification (and its components) and cytochrome P450 2C19 (CYP2C19)
      activity. Twenty-four subjects were grouped according to their Child-Pugh score
      as healthy, with mild hepatic impairment or with moderate hepatic impairment. The
      subjects were administered a single oral dose of escitalopram 20 mg, and blood
      was sampled up to 168 hours after dosage. The serum concentration of escitalopram
      was determined and the pharmacokinetics assessed by nonlinear mixed effect
      modeling. The CYP2C19 activity was measured from the urinary excretion ratio of
      S/R-mephenytoin. All subjects tolerated the treatment well, and no serious
      adverse events were reported. Predicted mean area under the curve from zero to
      infinity (AUC(inf)) values were 51% and 69% higher for patients with mild and
      moderate hepatic impairment (Child-Pugh classification), respectively, compared
      with healthy subjects. The best-fitting model showed an influence of CYP2C19
      activity on clearance and body weight on the volume of distribution for
      escitalopram. CYP2C19 activity is a better predictor of escitalopram clearance
      than is Child-Pugh classification.

PMID- 16584122
TI  - Blood pressure as an example of a biomarker that functions as a surrogate.
AB  - There are many important uses of biomarkers in drug development. An area of
      particular interest is the use of biomarkers as surrogate end points. Only a
      small minority of biomarkers are established surrogate end points. Blood pressure
      is an example of a surrogate end point accepted by both clinicians and
      regulators. It was a plausible surrogate because of the large epidemiologic
      databases demonstrating a correlation between elevated blood pressures and
      adverse cardiovascular outcomes. That plausibility has been supported, however,
      by the numerous placebo-controlled outcome studies evaluating several
      pharmacologically distinct agents that showed an effect on stroke and coronary
      heart disease outcomes from lowering blood pressure.

PMID- 16584123
TI  - Targeting opioid receptor heterodimers: strategies for screening and drug
      development.
AB  - G-protein-coupled receptors are a major target for the development of new
      marketable drugs. A growing number of studies have shown that these receptors
      could bind to their ligands, signal, and be internalized as dimers. Most of the
      evidence comes from in vitro studies, but recent studies using animal models
      support an important role for dimerization in vivo and in human pathologies. It
      is therefore becoming highly relevant to include dimerization in screening
      campaigns: the increased complexity reached by the ability to target 2 receptors
      should lead to the identification of more specific hits that could be developed
      into drugs with fewer side effects. In this review, we have summarized results
      from a series of studies characterizing the properties of G-protein-coupled
      receptor dimers using both in vitro and in vivo systems. Since opioid receptors
      exist as dimers and heterodimerization modulates their pharmacology, we have used
      them as a model system to develop strategies for the identification of compounds
      that will specifically bind and activate opioid receptor heterodimers: such
      compounds could represent the next generation of pain relievers with decreased
      side effects, including reduced drug abuse liability.

PMID- 16584124
TI  - Noncovalent interactions of drugs with immune receptors may mediate drug-induced
      hypersensitivity reactions.
AB  - Drug-induced hypersensitivity reactions are instructive examples of immune
      reactions against low molecular weight compounds. Classically, such reactions
      have been explained by the hapten concept, according to which the small antigen
      covalently modifies an endogenous protein; recent studies show strong
      associations of several HLA molecules with hypersensitivity. In recent years,
      however, evidence has become stronger that not all drugs need to bind covalently
      to the major histocompatibility complex (MHC)-peptide complex in order to trigger
      an immune response. Rather, some drugs may bind reversibly to the MHC or possibly
      to the T-cell receptor (TCR), eliciting immune reactions akin to the
      pharmacological activation of other receptors. While the exact mechanism is still
      a matter of debate, noncovalent drug presentation clearly leads to the activation
      of drug-specific T cells. In some patients with hypersensitivity, such a response
      may occur within hours of even the first exposure to the drug. Thus, the reaction
      to the drug may not be the result of a classical, primary response but rather be
      mediated by existing, preactivated T cells that display cross-reactivity for the
      drug and have additional (peptide) specificity as well. In this way, certain
      drugs may circumvent the checkpoints for immune activation imposed by the
      classical antigen processing and presentation mechanisms, which may help to
      explain the idiosyncratic nature of many drug hypersensitivity reactions.

PMID- 16584125
TI  - Effect of N-1 and N-2 residues on peptide deamidation rate in solution and solid
      state.
AB  - The deamidation kinetics of 7 model peptides (VYPNGA, VYGNGA, VFGNGA, VIGNGA,
      VGGNGA, VGPNGA, and VGYNGA) were studied at 70 degrees C in pH 10 buffer
      solutions and at 70 degrees C and 50% relative humidity in lyophilized solid
      formulations containing polyvinyl pyrrolidone (PVP). The disappearance of the
      model peptides from solution and solid-state formulations followed apparent first
      order kinetics, proceeding to completion in solution. In the solid state, the
      reactions showed plateaus with approximately 10% to 30% of the model peptides
      remaining; this was thought to be due to reversible complexation of the peptides
      and the PVP followed by slow dissociation of the complexes. The residues
      immediately N-terminal to asparagine (N-1, N-2) influenced the rate of
      deamidation significantly in the solid state but had minimal effect in solution.
      Increases in the volume and hydrophobicity of the N-1 and N-2 residues decreased
      the rate of deamidation in the solid state, but neither parameter alone
      adequately accounted for the observed effects. An empirical model using a linear
      combination of volume and hydrophobicity was developed; it showed that the
      influences of the volume and the hydrophobicity of the residues in the N-1 and N
      2 positions are approximately equally important for the N-1 and N-2 residues.

PMID- 16584126
TI  - Symbiotic relationship of pharmacogenetics and drugs of abuse.
AB  - Pharmacogenetics/pharmacogenomics is the study of how genetic variation affects
      pharmacology, the use of drugs to treat disease. When drug responses are
      predicted in advance, it is easier to tailor medications to different diseases
      and individuals. Pharmacogenetics provides the tools required to identify genetic
      predictors of probable drug response, drug efficacy, and drug-induced adverse
      events-identifications that would ideally precede treatment decisions. Drug abuse
      and addiction genetic data have advanced the field of pharmacogenetics in
      general. Although major findings have emerged, pharmacotherapy remains hindered
      by issues such as adverse events, time lag to drug efficacy, and heterogeneity of
      the disorders being treated. The sequencing of the human genome and high
      throughput technologies are enabling pharmacogenetics to have greater influence
      on treatment approaches. This review highlights key studies and identifies
      important genes in drug abuse pharmacogenetics that provide a basis for better
      diagnosis and treatment of drug abuse disorders.

PMID- 16584127
TI  - Mutant glycosyltransferases assist in the development of a targeted drug delivery
      system and contrast agents for MRI.
AB  - The availability of structural information on glycosyltransferases is beginning
      to make structure-based reengineering of these enzymes possible. Mutant
      glycosyltransferases have been generated that can transfer a sugar residue with a
      chemically reactive unique functional group to a sugar moiety of glycoproteins,
      glycolipids, and proteoglycans (glycoconjugates). The presence of modified sugar
      moiety on a glycoprotein makes it possible to link bioactive molecules via
      modified glycan chains, thereby assisting in the assembly of bionanoparticles
      that are useful for developing the targeted drug delivery system and contrast
      agents for magnetic resonance imaging. The reengineered recombinant
      glycosyltransferases also make it possible to (1) remodel the oligosaccharide
      chains of glycoprotein drugs, and (2) synthesize oligosaccharides for vaccine
      development.

PMID- 16584128
TI  - Development of the dopamine transporter selective RTI-336 as a pharmacotherapy
      for cocaine abuse.
AB  - The discovery and preclinical development of selective dopamine reuptake
      inhibitors as potential pharmacotherapies for treating cocaine addiction are
      presented. The studies are based on the hypothesis that a dopamine reuptake
      inhibitor is expected to partially substitute for cocaine, thus decreasing
      cocaine self-administration and minimizing the craving for cocaine. This type of
      indirect agonist therapy has been highly effective for treating smoking addiction
      (nicotine replacement therapy) and heroin addiction (methadone). To be an
      effective pharmacotherapy for cocaine addiction, the potential drug must be safe,
      long-acting, and have minimal abuse potential. We have developed several 3
      phenyltropane analogs that are potent dopamine uptake inhibitors, and some are
      selective for the dopamine transporter relative to the serotonin and
      norepinephrine transporters. In animal studies, these compounds substitute for
      cocaine, reduce the intake of cocaine in rats and rhesus monkeys trained to self
      administer cocaine, and have demonstrated a slow onset and long duration of
      action and lack of sensitization. The 3-phenyltropane analogs were also tested in
      a rhesus monkey self-administration model to define their abuse potential
      relative to cocaine. Based on these studies, 3beta-(4-chlorophenyl)-2beta-[3-(4'
      methylphenyl)isoxazol-5-yl]tropane (RTI-336) has been selected for preclinical
      development.

PMID- 16584129
TI  - Genetic factors in the predisposition to drug-induced hypersensitivity reactions.
AB  - Drug hypersensitivity reactions can occur with most drugs, although the
      frequency, severity, and clinical manifestations vary. Case reports have
      suggested that there may be familial clustering of drug hypersensitivity
      suggesting a genetic predisposition. As with most other forms of drug response,
      predisposition to drug hypersensitivity reactions is likely to be multifactorial
      and multigenic. Given the immune pathogenesis of these reactions, it is perhaps
      not surprising that the most significant genetic associations have been
      identified in the major histocompatibility complex for drugs such as abacavir,
      carbamazepine, and allopurinol. For abacavir, it has been suggested that
      preprescription genotyping for HLA-B*5701 in whites may reduce the incidence of
      hypersensitivity. It is likely that as our knowledge of variation in the human
      genome improves, coupled with improvements in technology, many more significant
      genetic predisposing factors for drug hypersensitivity are likely to be
      identified in the next decade. However, as we search for these genetic factors,
      it is important that we do not forget environmental predisposition, and to bear
      in mind that a genetic marker for drug hypersensitivity in one population may not
      necessarily be relevant for another population. Notwithstanding the advances in
      genetic technologies, the ultimate determinant of success in this area of
      research will be the identification and careful phenotyping of patients with drug
      hypersensitivity reactions. As we progress to whole genome scanning, in order to
      satisfy the requirements for adequate statistical power, the identification of
      large numbers of carefully phenotyped patients will be feasible only through
      international collaborations.

PMID- 16584132
TI  - The chinchilla microdialysis model for the study of antibiotic distribution to
      middle ear fluid.
AB  - In cases of slow or limited penetration of an antibiotic to the site of infection
      such as in acute otitis media (the middle ear), plasma levels of the agent may
      not reflect the concentrations that are relevant in determining clinical outcome.
      There is a need for a model that allows prediction of the time-course of unbound,
      pharmacologically active drug levels in middle ear fluid (MEF). This article
      introduces microdialysis as a sampling tool to measure unbound antibiotic
      concentrations in the MEF of the chinchilla, and briefly summarizes the results
      of studies of MEF penetration of a cephalosporin, a macrolide, and a ketolide
      antibiotic using this technique. The general concurrence of preliminary results
      of the chinchilla studies with clinical findings suggests that the chinchilla
      microdialysis model may be useful in predicting efficacy in patients.

PMID- 16584130
TI  - Selectivity and potency of cyclin-dependent kinase inhibitors.
AB  - Members of the cyclin-dependent kinase (CDK) family play key roles in various
      cellular processes. There are 11 members of the CDK family known till now. CDKs
      are activated by forming noncovalent complexes with cyclins such as A-, B-, C-, D
      (D1, D2, and D3), and E-type cyclins. Each isozyme of this family is responsible
      for particular aspects (cell signaling, transcription, etc) of the cell cycle,
      and some of the CDK isozymes are specific to certain kinds of tissues. Aberrant
      expression and overexpression of these kinases are evidenced in many disease
      conditions. Inhibition of isozymes of CDKs specifically can yield beneficiary
      treatment modalities with minimum side effects. More than 80 3-dimensional
      structures of CDK2, CDK5, and CDK6 complexed with inhibitors have been published.
      This review provides an understanding of the structural aspects of CDK isozymes
      and binding modes of various known CDK inhibitors so that these kinases can be
      better targeted for drug discovery and design. The amino acid residues that
      constitute the cyclin binding region, the substrate binding region, and the area
      around the adenosine triphosphate (ATP) binding site have been compared for CDK
      isozymes. Those amino acids at the ATP binding site that could be used to improve
      the potency and subtype specificity have been described.

PMID- 16584131
TI  - Recent progress in the computational prediction of aqueous solubility and
      absorption.
AB  - The computational prediction of aqueous solubility and/or human absorption has
      been the goal of many researchers in recent years. Such an in silico counterpart
      to the biopharmaceutical classification system (BCS) would have great utility.
      This review focuses on recent developments in the computational prediction of
      aqueous solubility, P-glycoprotein transport, and passive absorption. We find
      that, while great progress has been achieved, models that can reliably affect
      chemistry and development are still lacking. We briefly discuss aspects of
      emerging scientific understanding that may lead to breakthroughs in the
      computational modeling of these properties.

PMID- 16584133
TI  - Mechanisms of drug-induced liver injury.
AB  - The idiosyncratic nature and poor prognosis of drug-induced liver injury (DILI)
      make this type of reaction a major safety issue during drug development, as well
      as the most common cause for the withdrawal of drugs from the pharmaceutical
      market. The key to predicting and preventing DILI is understanding the underlying
      mechanisms. DILI is initiated by direct hepatotoxic effects of a drug, or a
      reactive metabolite of a drug. Parenchymal cell injury induces activation of
      innate and/or adaptive immune cells, which, in turn, produce proinflammatory and
      tissue hepatotoxic mediators, and/or mount immune reactions against drug
      associated antigens. Understanding the molecular and cellular elements associated
      with these pathways can help identify risk factors and may ultimately facilitate
      the development of strategies to predict and prevent DILI.

PMID- 16584134
TI  - Role of bioactivation in drug-induced hypersensitivity reactions.
AB  - Drug-induced hypersensitivity reactions are a major problem in both clinical
      treatment and drug development. This review covers recent developments in our
      understanding of the pathogenic mechanisms involved, with special focus on the
      potential role of metabolism and bioactivation in generating a chemical signal
      for activation of the immune system. The possible role of haptenation and
      neoantigen formation is discussed, alongside recent findings that challenge this
      paradigm. Additionally, the essential role of costimulation is examined, as are
      the potential points whereby costimulation may be driven by reactive metabolites.
      The relevance of local generation of metabolites in determining the location and
      character of a reaction is also covered.

PMID- 16584135
TI  - Current status of immunologic approaches to treating tobacco dependence: vaccines
      and nicotine-specific antibodies.
AB  - In contrast to current pharmacotherapies, immunologic approaches to treating
      tobacco dependence target the drug itself rather than the brain. This approach
      involves the use of nicotine-specific antibodies that bind nicotine in serum,
      resulting in a decrease in nicotine distribution to the brain and an increase in
      nicotine's elimination half-life. This review summarizes the literature examining
      the effects of immunologic interventions on the pharmacokinetics and behavioral
      effects of nicotine in animal models, as well as recent phase I and II clinical
      trials in humans. Studies using various vaccines and nicotine-specific antibodies
      in rodents have shown that immunization can significantly reduce the behavioral
      effects of nicotine that are relevant to tobacco dependence (eg, nicotine self
      administration). These findings provide proof of principle that immunologic
      interventions could have utility in the treatment of tobacco dependence. Thus
      far, phase I clinical trials of nicotine vaccines have not produced any serious
      adverse events in humans and have produced dose-dependent increases in serum
      antibody levels. Although preliminary data from these small trials suggest that
      vaccination can facilitate abstinence from tobacco use, more advance trials are
      needed. By acting outside the nervous system, immunologic approaches are less
      likely to produce the adverse side effects associated with current medications.
      In addition, the unique mechanism of action of immunotherapy makes it
      particularly suitable for combination with other pharmacological approaches.
      Taken together, the work completed to date provides substantial evidence that
      immunologic interventions could play an important role in future treatment
      strategies for tobacco dependence.

PMID- 16584137
TI  - Safety biomarkers and the clinical development of oncology therapeutics:
      considerations for cardiovascular safety and risk management.
AB  - During the clinical development of oncology therapeutics, new safety biomarkers
      are being employed with broad applications and implications for risk management
      and regulatory approval. Clinical laboratory results, used as safety biomarkers,
      can influence decision making at many levels during the clinical development and
      regulatory review of investigational cancer therapies, including (1) initial
      eligibility for protocol therapy; (2) analyses used to estimate and characterize
      the safety profile; and (3) treatment delivery, based on specific rules to modify
      or discontinue protocol treatment. With the increasing applications of safety
      biomarkers in clinical studies, consideration must be given to possible
      unintended consequences, including (1) restricted access to promising treatments;
      (2) delays in study completion; and (3) limitations to dose delivery, escalation,
      and determination of the maximal tolerated dose, the recommended phase 2 dose,
      and the optimal biologic dose selected for registration studies. This review will
      compare and contrast 2 biomarkers for cardiac safety that are employed in an
      increasing number of clinical programs designed for investigational oncology
      therapeutics: (1) assessment of left ventricular ejection fraction by either
      echocardiography or multigated acquisition scan; and (2) electrophysiological
      measurement of QT/QTc duration, assessed by electrocardiogram, for predicting
      risk of a potentially fatal arrhythmia called torsades de pointes. While these
      and other new safety biomarkers have major value in the development of oncology
      therapeutics, their applications require careful consideration to avoid
      unintended consequences that could negatively affect (1) the care of patients
      with advanced malignancy and (2) the advancement of promising new agents.

PMID- 16584136
TI  - CNS drug delivery: opioid peptides and the blood-brain barrier.
AB  - Peptides are key regulators in cellular and intercellular physiological responses
      and possess enormous promise for the treatment of pathological conditions. Opioid
      peptide activity within the central nervous system (CNS) is of particular
      interest for the treatment of pain owing to the elevated potency of peptides and
      the centrally mediated actions of pain processes. Despite this potential,
      peptides have seen limited use as clinically viable drugs for the treatment of
      pain. Reasons for the limited use are primarily based in the physiochemical and
      biochemical nature of peptides. Numerous approaches have been devised in an
      attempt to improve peptide drug delivery to the brain, with variable results.
      This review describes different approaches to peptide design/modification and
      provides examples of the value of these strategies to CNS delivery of peptide
      drugs. The various modes of modification of therapeutic peptides may be
      amalgamated, creating more efficacious "hybrid" peptides, with synergistic
      delivery to the CNS. The ongoing development of these strategies provides promise
      that peptide drugs may be useful for the treatment of pain and other
      neurologically-based disease states in the future.

PMID- 16584139
TI  - Formulation and in vitro, in vivo evaluation of extended- release matrix tablet
      of zidovudine: influence of combination of hydrophilic and hydrophobic matrix
      formers.
AB  - The aim of the present study was to prepare and characterize extended-release
      matrix tablets of zidovudine using hydrophilic Eudragit RLPO and RSPO alone or
      their combination with hydrophobic ethyl cellulose. Release kinetics was
      evaluated by using United States Pharmacopeia (USP)-22 type I dissolution
      apparatus. Scanning electron microscopy was used to visualize the effect of
      dissolution medium on matrix tablet surface. Furthermore, the in vitro and in
      vivo newly formulated sustained-release zidovudine tablets were compared with
      conventional marketed tablet (Zidovir, Cipla Ltd, Mumbai, India). The in-vitro
      drug release study revealed that either Eudragit preparation was able to sustain
      the drug release only for 6 hours (94.3% +/- 4.5% release). Combining Eudragit
      with ethyl cellulose sustained the drug release for 12 hours (88.1% +/- 4.1%
      release). Fitting the in vitro drug release data to Korsmeyer equation indicated
      that diffusion along with erosion could be the mechanism of drug release. In vivo
      investigation in rabbits showed sustained-release pharmacokinetic profile of
      zidovudine from the matrix tablets formulated using combination of Eudragits and
      ethylcellulose. In conclusion, the results suggest that the developed sustained
      release tablets of zidovudine could perform therapeutically better than
      conventional dosage forms, leading to improve efficacy and better patient
      compliance.

PMID- 16584138
TI  - Detergent-resistant membrane microdomains in the disposition of the lipid
      signaling molecule anandamide.
AB  - The endogenous cannabinoid anandamide is an agonist of the cannabinoid receptors
      CB1 and CB2, as well as transient receptor potential vanilloid type 1 and type 4
      ion channels. In recent years, there has been a great deal of interest in the
      cellular processes regulating the signaling of endocannabinoids such as
      anandamide. This is due largely to evidence that augmentation of cannabinergic
      tone might be therapeutically beneficial in the treatment of multiple disease
      states such as chronic pain, anxiety, multiple sclerosis, and neuropsychiatric
      disorders. Of particular interest are the cellular processes that regulate the
      cellular accumulation and metabolism of anandamide. Characterization of the
      process by which anandamide is internalized and metabolized by the cell may
      identify drug targets useful in the positive modulation of cannabinergic tone.
      Recently, we reported that detergent-resistant membrane microdomains known as
      lipid rafts play a role in the cellular accumulation of anandamide by mediating
      an endocytic process responsible for anandamide internalization. The enzyme
      primarily responsible for anandamide metabolism, fatty acid amide hydrolase, is
      excluded from lipid rafts. However, the metabolites of anandamide accumulate in
      these detergent-resistant membrane microdomains. There is some preliminary
      evidence that makes it reasonable to propose that anandamide metabolites enriched
      in lipid rafts may act as precursors to anandamide synthesis. Overall,
      experimental evidence is mounting that detergent-resistant membrane microdomains
      such as lipid rafts may play a role in the cellular regulation of anandamide
      inactivation and production.

PMID- 16584141
TI  - Quantitative measurement of indomethacin crystallinity in indomethacin-silica gel
      binary system using differential scanning calorimetry and X-ray powder
      diffractometry.
AB  - Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD)
      methods were developed for the quantitative analysis of the crystallinity of
      indomethacin (IMC) in IMC and silica gel (SG) binary system. The DSC calibration
      curve exhibited better linearity than that of XRPD. No phase transformation
      occurred in the IMC-SG mixtures during DSC measurement. The major sources of
      error in DSC measurements were inhomogeneous mixing and sampling. Analyzing the
      amount of IMC in the mixtures using high-performance liquid chromatography (HPLC)
      could reduce the sampling error. DSC demonstrated greater sensitivity and had
      less variation in measurement than XRPD in quantifying crystalline IMC in the IMC
      SG binary system.

PMID- 16584140
TI  - Evaluation of functional stability of quercetin as a raw material and in
      different topical formulations by its antilipoperoxidative activity.
AB  - The present study evaluates the antioxidant activity of the flavonol quercetin,
      and its functional stability as a raw material and when added in formulations.
      The iron-chelating activity was determined using the bathophenanthroline assay,
      and the functional stability was evaluated with the antilipoperoxidative assay.
      Raw material presented concentration-dependent antilipoperoxidative and iron
      chelating activities. The initial antilipoperoxidative activity of the raw
      material, cream and gel-cream were 63%, 78%, and 69%, respectively. There was no
      detectable loss of activity during 182 days (6 months) of storage at all tested
      temperatures (4 degrees C, room temperature [RT], 37 degrees C, and 45 degrees C)
      for the raw material. Considering the method variability of 10%, activity loss
      greater than 10% for nonionic cream was detected after 126 days at 4 degrees C
      (20.1%), decreasing thereafter to 22.2% after 182 days. At 45 degrees C, the loss
      of activity started after 182 days (13.2%). For the anionic gel-cream, activity
      loss started after 84 days (28.4%, 45 degrees C), decreasing after 182 days to
      40.3% at 45 degrees C. At 37 degrees C, activity loss was detected after 182 days
      (12%). In conclusion, the results suggest that the activity of quercetin depends
      on iron chelation, and its possible usefulness as a topical antioxidant to
      prevent oxidative stress-induced skin damage depends on maintaining its
      antilipoperoxidative activity stored at RT, which avoids special storage
      conditions.

PMID- 16584144
TI  - Evaluation of manometric temperature measurement, a process analytical technology
      tool for freeze-drying: part I, product temperature measurement.
AB  - This study examines the factors that may cause systematic errors in the
      manometric temperature measurement (MTM) procedure used to evaluate product
      temperature during primary drying. MTM was conducted during primary drying using
      different vial loads, and the MTM product temperatures were compared with
      temperatures directly measured by thermocouples. To clarify the impact of freeze
      drying load on MTM product temperature, simulation of the MTM vapor pressure rise
      was performed, and the results were compared with the experimental results. The
      effect of product temperature heterogeneity in MTM product temperature
      determination was investigated by comparing the MTM product temperatures with
      directly measured thermocouple product temperatures in systems differing in
      temperature heterogeneity. Both the simulated and experimental results showed
      that at least 50 vials (5 mL) were needed to give sufficiently rapid pressure
      rise during the MTM data collection period (25 seconds) in the freeze dryer, to
      allow accurate determination of the product temperature. The product temperature
      is location dependent, with higher temperature for vials on the edge of the array
      and lower temperature for the vials in the center of the array. The product
      temperature heterogeneity is also dependent upon the freeze-drying conditions. In
      product temperature heterogeneous systems, MTM measures a temperature close to
      the coldest product temperature, even if only a small fraction of the samples
      have the coldest product temperature. The MTM method is valid even at very low
      product temperature (-45 degrees C).

PMID- 16584142
TI  - Spray-dried mucoadhesive microspheres: preparation and transport through nasal
      cell monolayer.
AB  - The purpose of this research was to prepare spray-dried mucoadhesive microspheres
      for nasal delivery. Microspheres composed of hydroxypropyl methylcellulose (H),
      chitosan (CS), carbopol 934P (CP) and various combinations of these mucoadhesive
      polymers, and maltodextrin (M), colloidal silicon dioxide (A), and propylene
      glycol (P) as filler and shaper, were prepared by spray-drying technique. Using
      propranolol HCl as a model drug, microspheres were prepared at loadings exceeding
      80% and yields between 24% and 74%. Bulky, free flowing microspheres that had
      median particle size between 15 and 23 mum were obtained. Their zeta potential
      was according to the charge of polymer. Adhesion time of mucoadhesive
      microspheres on isolated pig intestine was ranked, CS > CP:H > CP > H, while the
      rank order of swelling was CP > CS > H. Increasing the amount of CP in CP:H
      formulations increased the percentage of swelling. Infrared (IR) spectra showed
      no interaction between excipients used except CS with acetic acid. The release of
      drug from CP and CP:H microspheres was slower than the release from H and CS
      microspheres, correlated to their viscosity and swelling. Long lag time from the
      CP microspheres could be shortened when combined with H. The permeation of drug
      through nasal cell monolayer corresponded to their release profiles. These
      microspheres affected the integrity of tight junctions, relative to their
      swelling and charge of polymer. Cell viability was not affected except from CS
      microspheres, but recovery could be obtained. In conclusion, spray-dried
      microspheres of H, CS, CP, and CP:H could be prepared to deliver drug through
      nasal cell monolayer via the opening of tight junction without cell damaging.

PMID- 16584143
TI  - Effect of formulation factors on in vitro permeation of moxifloxacin from aqueous
      drops through excised goat, sheep, and buffalo corneas.
AB  - The purpose of this investigation was to evaluate the effect of formulation
      factors on in vitro permeation of moxifloxacin from aqueous drop through freshly
      excised goat, sheep, and buffalo corneas. Aqueous isotonic ophthalmic solutions
      of moxifloxacin hydrochloride of different concentrations (pH 7.2) or 0.5%
      (wt/vol) solutions of different pH or 0.5% solutions (pH 7.2) containing
      different preservatives were made. Permeation characteristics of drug were
      evaluated by putting 1 mL formulation on freshly excised cornea (0.50 cm(2))
      fixed between donor and receptor compartments of an all-glass modified Franz
      diffusion cell and measuring the drug permeated in the receptor (containing 10 mL
      bicarbonate ringer at 37 degrees C under stirring) by spectrophotometry at 291
      nm, after 120 minutes. Statistical analysis was done by one-way analysis of
      variance (ANOVA) followed by Dunnett's test. Increase in drug concentration in
      the formulation resulted in an increase in the quantity permeated but a decrease
      in percentage permeation. Increase in pH of the solution from 5.5 to 7.2
      increased drug permeation, indicating pH-dependent transport. Compared with
      control formulation, moxifloxacin 0.5% (wt/vol) solution (pH 7.2) containing
      disodium edetate (EDTA) (0.01% wt/vol) produced significantly (P < .05) higher
      permeation with all the corneas. Formulation with benzyl alcohol significantly (P
      < .05) increased permeation with buffalo cornea compared with its control.
      Presence of benzalkonium chloride (BAK) (0.01% wt/vol) and EDTA (0.01% wt/vol) in
      the formulation increased permeation to the maximum with all the corneas. The
      results suggest that moxifloxacin 0.5% ophthalmic solution (pH 7.2) containing
      BAK (0.01%) and EDTA (0.01%) provides increased in vitro ocular availability
      through goat, sheep, and buffalo corneas.

PMID- 16584145
TI  - The effect of microwave thermal denaturation on release properties of bovine
      serum albumin and gluten matrices.
AB  - The purpose of this study was to compare the effects of denaturation by microwave
      irradiation on release properties of 2 physically different proteins. Matrices
      were prepared from water-soluble bovine serum albumin loaded with metoclopramide
      and sorbed with adequate amount of moisture were thermally denatured in a
      microwave oven. The release profile of the rather insoluble denatured albumin
      matrices followed the classical Fickian diffusion profile. The release rate was
      dependent on the degree of denaturation, which was highly dependent on the level
      of moisture originally absorbed by the albuminoidal matrices and the period of
      exposure to microwave energy. Conversely, attempts to reduce the rate of drug
      release through microwave irradiation of metoclopramide-loaded matrices prepared
      from water-insoluble gluten were futile. The denaturation process was shown to be
      limited to the relatively water-soluble protein core fraction, while aggregation
      between neighboring gluten proteins in the matrix was not achieved even in the
      presence of considerable amounts of sorbed water.

PMID- 16584146
TI  - Influence of aluminum tristearate and sucrose stearate as the dispersing agents
      on physical properties and release characteristics of eudragit RS microspheres.
AB  - The purpose of this research was to investigate the effects of different
      concentrations of polymer and sucrose stearate, aluminum tristearate as
      dispersing agents on microsphere properties and performance. The yield values of
      microspheres were over the 78%, and the encapsulation efficiencies were found to
      be approximately 73%. Particle sizes of microspheres prepared with aluminum
      tristearate were between 76 and 448 microm, while that of the microspheres
      containing sucrose stearate were between 521 and 2000 microm. Morphological and
      physicochemical properties of microspheres were investigated by scanning electron
      micrography and differential scanning calorimetry (DSC). DSC analysis indicated
      that verapamil hydrochloride formed a solid solution with acrylic polymers. In
      vitro release studies were performed using the flow-through cell method. While
      approximately 80% of drug was released from the microspheres containing aluminum
      tristearate in 480 minutes, the same amount of drug was released from
      microspheres containing sucrose stearate in only 60 minutes. Chemical structures
      and concentrations of the dispersing agents were clearly effective on the
      physical properties of microspheres and their drug-release characteristics.

PMID- 16584147
TI  - Intragastric floating drug delivery system of cefuroxime axetil: in vitro
      evaluation.
AB  - This investigation describes the development of an intragastric drug-delivery
      system for cefuroxime axetil. The 3(2) full factorial design was employed to
      evaluate contribution of hydroxypropyl methyl cellulose (HPMC) K4M/HPMC K100 LV
      ratio (polymer blend) and sodium lauryl sulfate (SLS) on drug release from HPMC
      matrices. Tablets were prepared using direct compression technique. Formulations
      were evaluated for in vitro buoyancy and drug release study using United States
      Pharmacopeia (USP) 24 paddle-type dissolution apparatus using 0.1N HCl as a
      dissolution medium. Multiple regression analysis was performed for factorial
      design batches to evaluate the response. All formulations had floating lag times
      below 2 minutes and constantly floated on dissolution medium for more than 8
      hours. It was found that polymer blend and SLS significantly affect the time
      required for 50% of drug release, percentage drug release at 12 hours, release
      rate constant, and diffusion exponent (P < .05). Also linear relationships were
      obtained between the amount of HPMC K100 LV and diffusion exponent as well as
      release rate constant. Kinetic treatment to dissolution profiles revealed drug
      release ranges from anomalous transport to case 1 transport, which was mainly
      dependent on both the independent variables.

PMID- 16584148
TI  - Improving cyclodextrin complexation of a new antihepatitis drug with glacial
      acetic acid.
AB  - The purpose of this study was to develop and evaluate a solid nonaqueous oral
      dosage form for a new hepatitis C drug, PG301029, which is insoluble and unstable
      in water. Hydroxypropyl-beta-cyclodextrin (HPbetaCD) and PG301029 were dissolved
      in glacial acetic acid. The acetic acid was removed by rotoevaporation such that
      the drug exists primarily in the complexed form. The stability of formulated
      PG301029 was determined upon dry storage and after reconstitution in simulated
      intestinal fluid (SIF), simulated gastric fluid (SGF), and water. Formulated
      PG301029 was found to be stable upon storage and can be reconstituted with water
      to a concentration 200 times that of the intrinsic solubility. Once
      reconstituted, the powder dissolves rapidly and PG301029 remains stable for 21
      hours in SGF, SIF, and water. The unique use of acetic acid and HPbetaCD results
      in a solid dosage form of PG301029 that is both soluble and stable in water.

PMID- 16584149
TI  - Formulation of a dry powder influenza vaccine for nasal delivery.
AB  - The purpose of this research was to prepare a dry powder vaccine formulation
      containing whole inactivated influenza virus (WIIV) and a mucoadhesive compound
      suitable for nasal delivery. Powders containing WIIV and either lactose or
      trehalose were produced by lyophilization. A micro-ball mill was used to reduce
      the lyophilized cake to sizes suitable for nasal delivery. Chitosan flakes were
      reduced in size using a cryo-milling technique. Milled powders were sieved
      between 45 and 125 microm aggregate sizes and characterized for particle size and
      distribution, morphology, and flow properties. Powders were blended in the micro
      ball mill without the ball. Lyophilization followed by milling produced
      irregularly shaped, polydisperse particles with a median primary particle
      diameter of approximately 21 microm and a yield of approximately 37% of particles
      in the 45 to 125 microm particle size range. Flow properties of lactose and
      trehalose powders after lyophilization followed by milling and sieving were
      similar. Cryo-milling produced a small yield of particles in the desired size
      range (<10%). Lyophilization followed by milling and sieving produced particles
      suitable for nasal delivery with different physicochemical properties as a
      function of processing conditions and components of the formulation. Further
      optimization of particle size and morphology is required for these powders to be
      suitable for clinical evaluation.

PMID- 16584150
TI  - Artemisia arborescens L essential oil-loaded solid lipid nanoparticles for
      potential agricultural application: preparation and characterization.
AB  - The aim of this study was to formulate a new delivery system for ecological
      pesticides by the incorporation of Artemisia arborescens L essential oil into
      solid lipid nanoparticles (SLN). Two different SLN formulations were prepared
      following the high-pressure homogenization technique using Compritol 888 ATO as
      lipid and Poloxamer 188 or Miranol Ultra C32 as surfactants. The SLN formulation
      particle size was determined using Photon correlation spectroscopy (PCS) and
      laser diffraction analysis (LD). The change of particle charge was studied by
      zeta potential (ZP) measurements, while the melting and recrystallization
      behavior was studied using differential scanning calorimetry (DSC). In vitro
      release studies of the essential oil were performed at 35 degrees C. Data showed
      a high physical stability for both formulations at various storage temperatures
      during 2 months of investigation. In particular, average diameter of Artemisia
      arborescens L essential oil-loaded SLN did not vary during storage and increased
      slightly after spraying the SLN dispersions. In vitro release experiments showed
      that SLN were able to reduce the rapid evaporation of essential oil if compared
      with the reference emulsions. Therefore, obtained results showed that the studied
      SLN formulations are suitable carriers in agriculture.

PMID- 16584151
TI  - Evaluation of the TSI aerosol impactor 3306/3321 system using a redesigned
      impactor stage with solution and suspension metered-dose inhalers.
AB  - The purpose of this research was to evaluate a redesigned impactor stage for the
      TSI Model 3306 Impactor Inlet with nozzles adjusted to obtain a target cut-point
      of 4.7 microm. It has been determined that the previous cut-point used in the
      Model 3306 was nominally closer to 4.14 microm, thus potentially impacting the
      characterization of aerosol mass. The reassessment of the Model 3306 was
      performed on 4 solution and 2 suspension metered-dose inhaler (MDI) formulations.
      The redesigned impactor stage resulted in a 5% to 6% increase in aerosol mass
      when compared with the previous impactor stage for the products Ventolin-HFA,
      Proventil-HFA, and 2 cyclosporin solution formulations with high ethanol
      concentrations (15% wt/wt). For the formulations with low ethanol concentrations
      (3% wt/wt), minimal differences were observed between the 2 cut-points. In
      addition, this study reevaluated the requirement of a vertical inlet extension
      length when using the TSI 3306/3321 system with the redesigned cut-point. It was
      shown that the use of a 20-cm extension provides mass and aerosol size
      distributions that are comparable to the Andersen 8-stage Cascade Impactor, for
      both solution and suspension MDIs. This work indicates that the TSI 3306/3321
      system is suitable for preformulation studies of both suspension and solution MDI
      systems.

PMID- 16584152
TI  - Micro-emultocrit technique: a valuable tool for determination of critical HLB
      value of emulsions.
AB  - The aim of this work was to develop a methodology for rapid determination of the
      critical hydrophilic-lipophilic balance (HLB) value of lipophilic fractions of
      emulsions. The emulsions were prepared by the spontaneous emulsification process
      with HLB value from 4.3 to 16.7. The preparations were stored at 2 different
      temperatures (25 degrees C and 4 degrees C) and their physicochemical behavior
      was evaluated by the micro-emultocrit technique and the long-term stability
      study. The experimental data show a reverse relationship between HLB values of
      the surfactant mixtures and emulsion stability. A close correlation between the
      results for both stability procedures was observed, suggesting the use of micro
      emultocrit to predict stabilities of such systems. In addition, it was found that
      the critical HLB of the Mygliol 812 was 15.367.

PMID- 16584153
TI  - Wet granulation in rotary processor and fluid bed: comparison of granule and
      tablet properties.
AB  - The aim of the present study was to investigate and compare granule and tablet
      properties of granules prepared by wet granulation in a rotary processor or a
      conventional fluid bed. For this purpose the working range of selected process
      variables was determined and a factorial study with 3 factors (equipment type,
      filler type, and liquid addition rate) and 1 covariate (fluidizing air flow rate)
      was performed. Two grades of calcium carbonate with different size and shape
      characteristics were applied, and the liquid addition and fluidizing air flow
      rates were investigated in the widest possible range. Dry mixtures of
      microcrystalline cellulose, polyvinyl povidone, calcium carbonate, and
      riboflavin, in a 10:5:84:1 ratio, were granulated in both types of equipment. The
      granulation end point was determined manually in the fluid bed and by torque
      measurements in the rotary processor. The filler type had a more pronounced
      effect on granular properties in the fluid bed, but the rotary processor showed a
      higher dependency on the investigated process variables. The rotary processor
      gave rise to more dense granules with better flow properties, but the fluid bed
      granules had slightly better compressional properties. Furthermore, the
      distribution of a low-dose drug was found to be more homogeneous in the rotary
      processor granules and tablets. Generally, wet granulation in a rotary processor
      was found to be a good alternative to conventional fluid bed granulation,
      especially when cohesive powders with poor flow properties or formulations with
      low drug content are to be granulated by a fluidizing air technique.

PMID- 16584154
TI  - Effect of pH on sublingual absorption of oxycodone hydrochloride.
AB  - The purpose of this study was to develop a sublingual spray drug delivery
      formulation of oxycodone and evaluate the effect of formulation pH on sublingual
      absorption of oxycodone for acute pain management using rabbit as the animal
      model. Using a new, sensitive, and specific liquid chromatography/mass
      spectrometry (LC/MS) with electrospray ionization detector assay, the absorption
      bioavailability of sublingual oxycodone was determined in rabbits by comparing
      plasma concentration after sublingual spray delivery with equivalent intravenous
      dose. The effect of formulation pH on sublingual absorption of oxycodone was also
      tested on rabbits that had received oxycodone sublingually at a dose of 0.1
      mg/0.1 mL (pH 4.0 and 9.0). Blood samples were collected at different time
      points, and plasma oxycodone concentrations were determined by LC/MS. Following
      administration of a 0.1 mg dose, the average C(max) values were found to be 64.9
      +/- 12.1 and 95.2 +/- 10.1 ng/mL, for pH 4.0 and 9.0, respectively. The area
      under the curve (AUC) values were found to be 5807.0, and 8965.3 ng.min/mL for
      formulation pH 4.0 and 9.0, respectively. The mean sublingual bioavailability of
      oxycodone was 45.4% +/- 20.1% and 70.1% +/- 17.9%, for pH 4.0 and 9.0,
      respectively. The formulation pH had no significant influence on oxycodone
      bioavailability (P < .05). A sublingual spray dosage form of oxycodone
      hydrochloride would be a good alternative for fast onset pain management,
      especially in children.

PMID- 16584156
TI  - Acoustic-resonance spectrometry as a process analytical technology for rapid and
      accurate tablet identification.
AB  - This research was performed to test the hypothesis that acoustic-resonance
      spectrometry (ARS) is able to rapidly and accurately differentiate tablets of
      similar size and shape. The US Food and Drug Administration frequently orders
      recalls of tablets because of labeling problems (eg, the wrong tablet appears in
      a bottle). A high-throughput, nondestructive method of online analysis and label
      comparison before shipping could obviate the need for recall or disposal of a
      batch of mislabeled drugs, thus saving a company considerable expense and
      preventing a major safety risk. ARS is accurate and precise as well as
      inexpensive and nondestructive, and the sensor is constructed from readily
      available parts, suggesting utility as a process analytical technology (PAT). To
      test the classification ability of ARS, 5 common household tablets of similar
      size and shape were chosen for analysis (aspirin, ibuprofen, acetaminophen,
      vitamin C, and vitamin B12). The measures of successful tablet identification
      were intertablet distances in nonparametric multidimensional standard deviations
      (MSDs) greater than 3 and intratablet MSDs less than 3, as calculated from an
      extended bootstrap error-adjusted single sample technique. The average
      intertablet MSD was 65.64, while the average intratablet MSD from cross
      validation was 1.91. Tablet mass (r (2) = 0.977), thickness (r (2) = 0.977), and
      density (r (2) = 0.900) were measured very accurately from the AR spectra, each
      with less than 10% error. Tablets were identified correctly with only 250 ms data
      collection time. These results demonstrate that ARS effectively identified and
      characterized the 5 types of tablets and could potentially serve as a rapid high
      throughput online pharmaceutical sensor.

PMID- 16584155
TI  - Use of hydrophilic natural gums in formulation of sustained-release matrix
      tablets of tramadol hydrochloride.
AB  - The objective of this work was to develop matrix sustained-release tablets of
      highly water-soluble tramadol HCl using natural gums (xanthan [X gum] and guar [G
      gum]) as cost-effective, nontoxic, easily available, and suitable hydrophilic
      matrix systems compared with the extensively investigated hydrophilic matrices
      (ie, hydroxypropyl methylcellulose [HPMC]/carboxymethyl cellulose [CMC] with
      respect to in vitro drug release rate) and hydration rate of the polymers. Matrix
      tablets of tramadol (dose 100 mg) were produced by direct compression method.
      Different ratios of 100:0, 80:20, 60:40, 20:80, 0:100 of G gum (or X):HPMC, X
      gum:G gum, and triple mixture of these polymers (G gum, X gum, HPMC) were
      applied. After evaluation of physical characteristics of tablets, the dissolution
      test was performed in the phosphate buffer media (pH 7.4) up to 8 hours. Tablets
      with only X had the highest mean dissolution time (MDT), the least dissolution
      efficiency (DE(8)%), and released the drug following a zero-order model via
      swelling, diffusion, and erosion mechanisms. Guar gum alone could not efficiently
      control the drug release, while X and all combinations of natural gums with HPMC
      could retard tramadol HCl release. However, according to the similarity factor
      (f(2) ), pure HPMC and H(8)G(2) were the most similar formulations to Topalgic-LP
      as the reference standard.

PMID- 16584157
TI  - Solubility prediction in octanol: a technical note.
AB  - The purpose of this work was to derive an equation for the rapid estimation of
      octanol solubilities of organic compounds. Solubilities ranging over 4 orders of
      magnitude were predicted with an average absolute error of 0.39 logarithmic units
      using melting point alone. The greatest error in prediction occurred for strongly
      bonded compounds.

PMID- 16584158
TI  - Preparation and characterization of eudragit retard nanosuspensions for the
      ocular delivery of cloricromene.
AB  - The purpose of this study was to improve the stability of cloricromene (AD6) in
      ophthalmic formulations and its drug availability at the ocular level. To this
      end, AD6-loaded polymeric nanoparticle suspensions were made using inert polymer
      resins (Eudragit RS100 and RL100). We modified the quasi-emulsion solvent
      diffusion technique by varying some formulation parameters (the drug-to-polymer
      ratio, the total drug and polymer amount, and the stirring speed). The chemical
      stability of AD6 in the nanosuspensions was assessed by preparing some
      formulations using (unbuffered) isotonic saline or a pH 7 phosphate buffer
      solution as the dispersing medium. The formulations were stored at 4 degrees C,
      and the rate of degradation of AD6 was followed by high performance liquid
      chromatography (HPLC). The obtained nanosuspensions showed mean sizes and a
      positive surface charge (zeta-potential) that make them suitable for an
      ophthalmic application; these properties were maintained upon storage at 4
      degrees C for several months. In vitro dissolution tests confirmed a modified
      release of the drug from the polymer matrixes. Nanosuspensions prepared with
      saline solution and no or lower amounts of surfactant (Tween 80) showed an
      enhanced stability of the ester drug for several months, with respect to an AD6
      aqueous solution. Based on the technological results, AD6-loaded Eudragit Retard
      nanoparticle suspensions appear to offer promise as a means to improving the
      shelf life and bioavailability of this drug after ophthalmic application.

PMID- 16584159
TI  - Porous polystyrene beads as carriers for self-emulsifying system containing
      loratadine.
AB  - The aim of this study was to formulate a self-emulsifying system (SES) containing
      a lipophilic drug, loratadine, and to explore the potential of preformed porous
      polystyrene beads (PPB) to act as carriers for such SES. Isotropic SES was
      formulated, which comprised Captex 200 (63% wt/wt), Cremophore EL (16% wt/wt),
      Capmul MCM (16% wt/wt), and loratadine (5% wt/wt). SES was evaluated for droplet
      size, drug content, and in vitro drug release. SES was loaded into preformed and
      characterized PPB using solvent evaporation method. SES-loaded PPB were evaluated
      using scanning electron microscopy (SEM) for density, specific surface area
      (S(BET)), loading efficiency, drug content, and in vitro drug release. After SES
      loading, specific surface area reduced drastically, indicating filling of PPB
      micropores with SES. Loading efficiency was least for small size (SS) and
      comparable for medium size (MS) and large size (LS) PPB fractions. In vitro drug
      release was rapid in case of SS beads due to the presence of SES near to surface.
      LS fraction showed inadequate drug release owing to presence of deeper micropores
      that resisted outward diffusion of entrapped SES. Leaching of SES from micropores
      was the rate-limiting step for drug release. Geometrical features such as bead
      size and pore architecture of PPB were found to govern the loading efficiency and
      in vitro drug release from SES-loaded PPB.

PMID- 16584160
TI  - Quantitation of drug content in a low dosage formulation by transmission near
      infrared spectroscopy.
AB  - A transmission near infrared (NIR) spectroscopic method has been developed for
      the nondestructive determination of drug content in tablets with less than 1%
      weight of active ingredient per weight of formulation (m/m) drug content. Tablets
      were manufactured with drug concentrations of approximately 0.5%, 0.7%, and 1.0%
      (m/m) and ranging in drug content from 0.71 to 2.51 mg per tablet. Transmission
      NIR spectra were obtained for 110 tablets that constituted the training set for
      the calibration model developed with partial least squares regression. The
      reference method for the calibration model was a validated UV spectrophotometric
      method. Several data preprocessing methods were used to reduce the effect of
      scattering on the NIR spectra and base the calibration model on spectral changes
      related to the drug concentration changes. The final calibration model included
      the spectral range from 11 216 to 8662 cm(-1), the standard normal variate (SNV),
      and first derivative spectral pretreatments. This model was used to predict an
      independent set of 48 tablets with a root mean standard error of prediction
      (RMSEP) of 0.14 mg, and a bias of only -0.05 mg per tablet. The study showed that
      transmission NIR spectroscopy is a viable alternative for nondestructive testing
      of low drug content tablets, available for the analysis of large numbers of
      tablets during process development and as a tool to detect drug agglomeration and
      evaluate process improvement efforts.

PMID- 16584161
TI  - Formulation and optimization of controlled release mucoadhesive tablets of
      atenolol using response surface methodology.
AB  - The aim of the current study was to design oral controlled release mucoadhesive
      compressed hydrophilic matrices of atenolol and to optimize the drug release
      profile and bioadhesion using response surface methodology. Tablets were prepared
      by direct compression and evaluated for bioadhesive strength and in vitro
      dissolution parameters. A central composite design for 2 factors at 3 levels each
      was employed to systematically optimize drug release profile and bioadhesive
      strength. Carbopol 934P and sodium carboxymethylcellulose were taken as the
      independent variables. Response surface plots and contour plots were drawn, and
      optimum formulations were selected by feasibility and grid searches. Compressed
      matrices exhibited non-Fickian drug release kinetics approaching zero-order, as
      the value of release rate exponent (n) varied between 0.6672 and 0.8646,
      resulting in regulated and complete release until 24 hours. Both the polymers had
      significant effect on the bioadhesive strength of the tablets, measured as force
      of detachment against porcine gastric mucosa (P < .001). Polynomial mathematical
      models, generated for various response variables using multiple linear regression
      analysis, were found to be statistically significant (P < .01). Validation of
      optimization study, performed using 8 confirmatory runs, indicated very high
      degree of prognostic ability of response surface methodology, with mean
      percentage error (+/- SD) as -0.0072 +/- 1.087. Besides unraveling the effect of
      the 2 factors on the various response variables, the study helped in finding the
      optimum formulation with excellent bioadhesive strength and controlled release.

PMID- 16584162
TI  - Development and in vitro evaluation of Chitosan-Eudragit RS 30D composite wound
      dressings.
AB  - The purpose of this research was to design and evaluate chitosan-based films
      intended for wound dressing application. Required properties for successful wound
      dressing, such as liquid uptake, vapor and oxygen penetration, bioadhesiveness,
      and film elasticity, were examined. Water uptake and vapor penetration of the
      films were determined gravimetrically, while oxygen penetration was determined by
      Winkler's method. The bioadhesive properties were determined with an in-house
      pulley system instrument using a pig gut model. Film elasticity was determined
      with a stretch test using an Instron apparatus. The results showed that pure
      chitosan films exhibited relatively high liquid uptake and the adsorption tended
      to decrease with the addition of Eudragit RS 30D. Moisture vapor and oxygen were
      found to be able to penetrate through all film formulations in comparable
      amounts. The bioadhesiveness test tended to show lower bioadhesive properties
      with the addition of Eudragit RS 30D. The formulation containing only chitosan
      exhibited low elongation of the film at 2 N, but the film elasticity increased
      with the addition of Eudragit RS 30D. In conclusion, the addition of Eudragit RS
      30D could improve a film's mechanical properties but lower its bioadhesiveness.

PMID- 16584163
TI  - Determination of aqueous solubility by heating and equilibration: a technical
      note.

PMID- 16584164
TI  - Reformulation of a new vancomycin analog: an example of the importance of buffer
      species and strength.
AB  - The purpose of this research was to use our previously validated dynamic
      injection apparatus as a rapid method for screening pH-adjusted formulations of a
      new vancomycin analog, Van-An, for their potential to precipitate upon dilution.
      In 1 vial, Van-An was reconstituted according to the manufacturer's instructions.
      In a separate vial, the Van-An formulation's existing phosphate buffer species
      was supplemented with acetate buffer, which has a pKa in the desired range:
      between the pH values of the formulation (pH 3.9) and blood (pH 7.4). The
      formulations were injected using the dynamic injection apparatus into a flowing
      stream of isotonic Sorensen's phosphate buffer at rates of 0.25, 0.5, 1, and 2
      mL/min. The peaks obtained with the spectrophotometer were reproducible for each
      injection rate/formulation combination. For the phosphate-buffered formulation,
      the least amount of precipitation was obtained at the 0.25 mL/min injection rate.
      Acetate buffer was able to substantially reduce such precipitation, even at the
      highest injection rate. The opacity peaks for the formulation with the acetate
      addition were significantly smaller (P < .05) than those obtained for the
      unaltered formulation at all 4 injection rates. The results suggest that acetate
      is a better buffer species than phosphate for the pH range defined. Furthermore,
      we present evidence to support a generally applicable approach to screening new
      formulations of drug products that may be clinically useful for reducing the
      incidence of phlebitis in humans.

PMID- 16584165
TI  - In vivo characterization of monolithic matrix type transdermal drug delivery
      systems of pinacidil monohydrate: a technical note.

PMID- 16584166
TI  - Local and average gloss from flat-faced sodium chloride tablets.
AB  - The purpose of this study was to detect local gloss and surface structure changes
      of sodium chloride tablets. The changes in surface structure were reflected by
      gloss variation, which was measured using a diffractive optical element-based
      glossmeter (DOG). By scanning a surface area, we constructed a 2-dimensional
      gloss map that characterized the tablet's surface structure. The gloss variation
      results were compared with scanning electron microscopy (SEM) images and average
      surface roughness values that were measured by conventional diamond stylus
      profilometry. The profilometry data showed a decrease in tablet surface roughness
      as a function of compression force. In general, a smoother surface contributes to
      higher average gloss values. The average gloss values for this material, in
      contrast, showed a decrease as a function of the compression force. The sequence
      of particle fragmentation and deformation together with crack formation in sodium
      chloride particles resulted in a loss of gloss for single sodium chloride
      particles at the tablet surfaces, which could be detected by the DOG. These
      results were supported by the SEM images. The results show that detailed
      information regarding tablets' surface structure changes can be obtained by
      detection of local gloss variation and average gloss.

PMID- 16584167
TI  - Preliminary brain-targeting studies on intranasal mucoadhesive microemulsions of
      sumatriptan.
AB  - The aim of this investigation was to prepare microemulsions containing
      sumatriptan (ST) and sumatriptan succinate (SS) to accomplish rapid delivery of
      drug to the brain in acute attacks of migraine and perform comparative in vivo
      evaluation in rats. Sumatriptan microemulsions (SME)/sumatriptan succinate
      microemulsions (SSME) were prepared using titration method and characterized for
      drug content, globule size and size distribution, and zeta potential.
      Biodistribution of SME, SSME, sumatriptan solution (SSS), and marketed product
      (SMP) in the brain and blood of Swiss albino rats following intranasal and
      intravenous (IV) administrations were examined using optimized technetium-labeled
      ((99m)Tc-labeled) ST formulations. The pharmacokinetic parameters, drug targeting
      efficiency (DTE), and direct drug transport (DTP) were derived. Gamma
      scintigraphy imaging of rat brain following IV and intranasal administrations
      were performed to ascertain the localization of drug. SME and SSME were
      transparent and stable with mean globule size 38 +/- 20 nm and zeta potential
      between -35 to -55 mV. Brain/blood uptake ratios at 0.5 hour following IV
      administration of SME and intranasal administrations of SME, SMME, and SSS were
      found to be 0.20, 0.50, 0.60, and 0.26, respectively, suggesting effective
      transport of drug following intranasal administration of microemulsions. Higher
      DTE and DTP for mucoadhesive microemulsions indicated more effective targeting
      following intranasal administration and best brain targeting of ST from
      mucoadhesive microemulsions. Rat brain scintigraphy endorsed higher uptake of ST
      into the brain. Studies conclusively demonstrated rapid and larger extent of
      transport of microemulsion of ST compared with microemulsion of SS, SMP, and SSS
      into the rat brain. Hence, intranasal delivery of ST microemulsion developed in
      this investigation can play a promising role in the treatment of acute attacks of
      migraine.

PMID- 16584168
TI  - The effect of residual water on antacid properties of sucralfate gel dried by
      microwaves.
AB  - The aim of this work was to study the acid neutralization characteristics of
      microwave-dried sucralfate gel in relation to the water content and physical
      structure of the substance. Several dried sucralfate gels were compared with
      humid sucralfate gel and sucralfate nongel powder in terms of neutralization rate
      and buffering capacity. Humid sucralfate gel and microwave-dried gel exhibited
      antacid effectiveness. In particular, the neutralization rate of dried gel
      powders was inversely related to the water content: as the water content of dried
      powders decreased, the acid reaction rate linearly increased. The relationship
      was due to the different morphology of dried sucralfate gels. In fact, the
      porosity of the dried samples increased with the water reduction. However, the
      acid neutralization equivalent revealed that the dried sucralfate gel became more
      resistant to acid attack in the case of water content below 42%. Then, the
      microwave drying procedure had the opposite effect on the reactivity of the
      aluminum hydroxide component of dried sucralfate gel powders, since the rate of
      the reaction increased whereas the buffering capacity decreased as the amount of
      water was reduced.

PMID- 16584169
TI  - Novel effect of C75 on carnitine palmitoyltransferase I activity and palmitate
      oxidation.
AB  - C75 is a potential drug for the treatment of obesity. It was first identified as
      a competitive, irreversible inhibitor of fatty acid synthase (FAS). It has also
      been described as a malonyl-CoA analogue that antagonizes the allosteric
      inhibitory effect of malonyl-CoA on carnitine palmitoyltransferase I (CPT I), the
      main regulatory enzyme involved in fatty acid oxidation. On the basis of MALDI
      TOF analysis, we now provide evidence that C75 can be transformed to its C75-CoA
      derivative. Unlike the activation produced by C75, the CoA derivative is a potent
      competitive inhibitor that binds tightly but reversibly to CPT I. IC50 values for
      yeast-overexpressed L- or M-CPT I isoforms, as well as for purified mitochondria
      from rat liver and muscle, were within the same range as those observed for
      etomoxiryl-CoA, a potent inhibitor of CPT I. When a pancreatic INS(823/13),
      muscle L6E9, or kidney HEK293 cell line was incubated directly with C75, fatty
      acid oxidation was inhibited. This suggests that C75 could be transformed in the
      cell to its C75-CoA derivative, inhibiting CPT I activity and consequently fatty
      acid oxidation. In vivo, a single intraperitoneal injection of C75 in mice
      produced short-term inhibition of CPT I activity in mitochondria from the liver,
      soleus, and pancreas, indicating that C75 could be transformed to its C75-CoA
      derivative in these tissues. Finally, in silico molecular docking studies showed
      that C75-CoA occupies the same pocket in CPT I as palmitoyl-CoA, suggesting an
      inhibiting mechanism based on mutual exclusion. Overall, our results describe a
      novel role for C75 in CPT I activity, highlighting the inhibitory effect of its
      C75-CoA derivative.

PMID- 16584170
TI  - Identification of a novel noncatalytic bicarbonate binding site in eubacterial
      beta-carbonic anhydrase.
AB  - The structures of beta class carbonic anhydrases (beta-CAs) determined so far
      fall into two distinct subclasses based on the observed coordination of the
      catalytic zinc (Zn2+) ion. The subclass of beta-CAs that coordinate Zn2+
      tetrahedrally with four protein-derived ligands is represented by the structures
      of orthologues from Porphyridium purpureum, Escherichia coli, and Mycobacterium
      tuberculosis. Here we present the structure of an additional member of that
      subclass, that from Haemophilus influenzae, as well as detailed kinetic analysis,
      revealing the correspondence between structural classification and kinetic
      profile for this subclass. In addition, we identify a unique, noncatalytic
      binding mode for the substrate bicarbonate that occurs in both the H. influenzae
      and E. coli enzymes. The kinetic and structural analysis indicates that binding
      of bicarbonate in this site of the enzyme may modulate its activity by
      influencing a pH-dependent, cooperative transition between active and inactive
      forms. We hypothesize that the two structural subclasses of beta-CAs may provide
      models for the proposed active and inactive forms of the H. influenzae and E.
      coli enzymes.

PMID- 16584171
TI  - FTIR study of the photoisomerization processes in the 13-cis and all-trans forms
      of Anabaena sensory rhodopsin at 77 K.
AB  - Archaeal-type rhodopsins can accommodate either all-trans- or 13-cis,15-syn
      retinal in their chromophore binding site in the dark, but only the former isomer
      is functionally important. In contrast, Anabaena sensory rhodopsin (ASR), an
      archaeal-type rhodopsin found in eubacteria, exhibits a photochromic
      interconversion of both forms, suggesting that ASR functions as a photosensor
      which interacts with its 14 kDa soluble transducer differently in the all-trans
      and 13-cis,15-syn forms. In this study, we applied low-temperature Fourier
      transform infrared (FTIR) spectroscopy to the 13-cis,15-syn form of ASR (13C-ASR)
      at 77 K and compared the local structure around the chromophore and its
      structural changes upon retinal photoisomerization with those of the all-trans
      form (AT-ASR) [Furutani, Y., Kawanabe, A., Jung, K. H., and Kandori, H. (2005)
      Biochemistry 44, 12287-12296]. By use of [zeta-15N]lysine-labeled ASR, we
      identified the N-D stretching vibrations of the Schiff base (in D2O) at 2165 cm(
      1) for 13C-ASR and at 2163 and 2125 cm(-1) for AT-ASR. The frequencies indicate
      strong hydrogen bonds of the Schiff base with a water molecule for both 13C-ASR
      and AT-ASR. In contrast, the N-D stretching vibration appears at 2351 cm(-1) and
      at 2483 cm(-1) for the K states of 13C-ASR (13C-ASR(K)) and AT-ASR (AT-ASR(K)),
      respectively, indicating that the Schiff base still forms a hydrogen bond in 13C
      ASR(K). Rotational motion of the Schiff base upon retinal isomerization is
      probably smaller for 13C-ASR than for AT-ASR, the latter altering hydrogen
      bonding of the Schiff base similar to bacteriorhodopsin (BR), a light-driven
      proton pump. Appearance of several hydrogen-out-of-plane vibrations and amide I
      vibrations in 13C-ASR(K), but not in AT-ASR(K), suggests that structural changes
      are distributed widely along the polyene chain for 13C-ASR. On the other hand,
      retinal photoisomerization in AT-ASR breaks the hydrogen bond of the Schiff base,
      and localized structural changes in the Schiff base region are induced.

PMID- 16584172
TI  - Transmembrane helix-helix association: relative stabilities at low pH.
AB  - We have previously studied the unfolding equilibrium of bacterioopsin in a single
      phase solvent, using Forster mechanism fluorescence resonance energy transfer
      (FRET) as a probe, from tryptophan donors to a dansyl acceptor. We observed an
      apparent unfolding transition in bacterioopsin perturbed by increasing ethanol
      concentrations [Nannepaga et al. (2004) Biochemistry 43, 50-59]. We have further
      investigated this transition and find that the unfolding is pH-dependent. We have
      now measured the apparent pK of acid-induced unfolding of bacterioopsin in 90%
      ethanol. When the acceptor is on helix B (Lys 41), the apparent pK for unfolding
      is 4.75; on the EF connecting loop (Cys 163), 5.15; and on helix G (Cys 222),
      5.75. Five-helix proteolytic fragments are less stable. The apparent unfolding
      pKs are 5.46 for residues 72-248 (Cys 163) and 7.36 for residues 1-166 (Lys 41).
      When interpreted in terms of a simple equilibrium model for unfolding, the
      apparent pKs give relative free energies of unfolding in the range of -0.54 to 
      3.5 kcal/mol. The results suggest that the C-terminal helix of bacterioopsin is
      less stably folded than the N-terminal helices. We analyzed the pairwise helix
      helix interaction surfaces of bacteriorhodopsin and three other seven
      transmembrane-helix proteins on the basis of crystal structures. The results show
      that the interaction surfaces are smoother and the helix axis separations are
      closer in the amino-terminal two-thirds of the proteins compared with the
      carboxyl-terminal one-third. However, the F helix is important in stabilizing the
      folded structure, as shown by the instability of the 1-166 fragment. Considering
      the high-resolution crystal structure of bacteriorhodopsin, there are no obvious
      helix-helix interactions involving protein side chains which would be
      destabilized by protonation at the estimated pH of the unfolding transitions.
      However, a number of helix-bridging water molecules could become protonated,
      thereby weakening the helix-helix interactions.

PMID- 16584173
TI  - Structure of phenoxazinone synthase from Streptomyces antibioticus reveals a new
      type 2 copper center.
AB  - The multicopper oxidase phenoxazinone synthase (PHS) catalyzes the penultimate
      step in the biosynthesis of the antibiotic actinomycin D by Streptomyces
      antibioticus. PHS exists in two oligomeric forms: a dimeric form and a hexameric
      form, with older actinomycin-producing cultures containing predominately the
      hexameric form. The structure of hexameric PHS has been determined using X-ray
      diffraction to a resolution limit of 2.30 A and is found to contain several
      unexpected and distinctive features. The structure forms a hexameric ring that is
      centered on a pseudo 6-fold axis and has an outer diameter of 185 A with a large
      central cavity that has a diameter of 50 A. This hexameric structure is
      stabilized by a long loop connecting two domains; bound to this long loop is a
      fifth copper atom that is present as a type 2 copper. This copper atom is not
      present in any other multicopper oxidase, and its presence appears to stabilize
      the hexameric structure.

PMID- 16584174
TI  - Heterologous overexpression and purification of cytochrome c' from Rhodobacter
      capsulatus and a mutant (K42E) in the dimerization region. Mutation does not
      alter oligomerization but impacts the heme iron spin state and nitric oxide
      binding properties.
AB  - Rhodobacter capsulatus cytochrome c' (RCCP) has been overexpressed in Escherichia
      coli, and its spectroscopic and ligand-binding properties have been investigated.
      It is concluded that the heterologously expressed protein is assembled correctly,
      as judged by UV-vis absorption, EPR, and resonance Raman (RR) spectroscopy of the
      unligated protein as well as forms in which the heme is ligated by CO or NO. To
      probe the oligomerization state of RCCP and its potential influence on heme
      reactivity, we have compared the properties of wild-type RCCP with a mutant
      (K42E) that lacks a salt bridge at the subunit interface. Analytical
      ultracentrifugation indicates that wild-type and K42E proteins are both monomeric
      in solution, contrary to the homodimeric structure of the crystalline state.
      Surprisingly, the K42E mutation produces a number of changes at the heme center
      (nearly 20 A distant), including perturbation of the ferric spin-state
      equilibrium and a change in the ferrous heme-nitrosyl complex from a six
      coordinate/five-coordinate mixture to a predominantly five-coordinate heme-NO
      species. RR spectra indicate that ferrous K42E and wild-type RCCP both have
      relatively high Fe-His stretching frequencies, suggesting that the more favored
      five-coordinate heme-nitrosyl formation in K42E is not caused by a weaker Fe2+
      His bond. Nevertheless, the altered reactivity of ferrous K42E with NO, together
      with its modified ferric spin state, shows that structural changes originating at
      the dimer interface can affect the properties of the heme center, raising the
      exciting possibility that intermolecular encounters at the protein surface might
      modulate the reactivity of cytochrome c' in vivo.

PMID- 16584175
TI  - Distinct binding of cholesterol and 5beta-cholestane-3alpha,7alpha,12alpha-triol
      to cytochrome P450 27A1: evidence from modeling and site-directed mutagenesis
      studies.
AB  - Cytochrome P450 27A1 (P450 27A1 or CYP27A1) is an important enzyme that
      participates in different pathways of cholesterol degradation as well as in the
      activation of vitamin D(3). Several approaches were utilized to investigate how
      two physiological substrates, cholesterol and 5beta-cholestane
      3alpha,7alpha,12alpha-triol, interact with CYP27A1. The enzyme active site was
      first probed spectrally by assessing binding of the two substrates and five
      substrate analogues followed by computer modeling and site-directed mutagenesis.
      The computer models suggest that the spatial positions and orientations of
      cholesterol and 5beta-cholestane-3alpha,7alpha,12alpha-triol are different in the
      enzyme active site. As a result, some of the active site residues interact with
      both substrates, although they are situated differently relative to each steroid,
      and some residues bind only one substrate. Mutation of the overlapping substrate
      contact residues (W100, H103, T110, M301C, V367, I481, and V482) affected CYP27A1
      binding and enzyme activity in a substrate-dependent manner and allowed
      identification of several important side chains. T110 is proposed to interact
      with the 12alpha-hydroxyl of 5beta-cholestane-3alpha,7alpha,12alpha-triol,
      whereas V367 seems to be crucial for correct positioning of the cholesterol C26
      methyl group and for regioselective hydroxylation of this substrate. Distinct
      binding of the CYP27A1 substrates may provide insight into why phenotypic
      manifestations of cerebrotendinous xanthomatosis, a disease associated with
      CYP27A1 deficiency, are so diverse.

PMID- 16584177
TI  - Identification of a novel subunit of respiratory complex I from Thermus
      thermophilus.
AB  - The hydrophilic domain (peripheral arm) of the proton-translocating NADH:quinone
      oxidoreductase (complex I) from the thermophilic organism Thermus thermophilus
      HB8 has been purified and characterized. The subcomplex is stable in sodium
      dodecyl sulfate up to 80 degrees C. Of nine iron-sulfur clusters, four to five
      (one or two binuclear and three tetranuclear) could be detected by EPR in the
      NADH-reduced enzyme. The preparation consists of eight different polypeptides.
      Seven of them have been positively identified by peptide mass mapping and N
      terminal sequencing as known hydrophilic subunits of T. thermophilus complex I.
      The eighth polypeptide copurified with the subcomplex at all stages, is strongly
      associated with the other subunits, and is present in crystals of the subcomplex,
      used for X-ray data collection. Therefore, it has been identified as a novel
      complex I subunit and named Nqo15. It is encoded in a locus separate from the nqo
      operon, containing the 14 other known complex I genes. ORFs encoding Nqo15
      homologues are present in the genomes of the closest relatives of T.
      thermophilus. Our data show that, contrary to previous assumptions, bacterial
      complex I can contain proteins in addition to a "core" complement of 14 subunits.

PMID- 16584176
TI  - Interaction between mitochondrial CYP27B1 and adrenodoxin: role of arginine 458
      of mouse CYP27B1.
AB  - A molecular modeling study of CYP27B1 suggests that Arg458 of mouse CYP27B1 is
      involved in interaction with adrenodoxin (ADX). Thus, we generated CYP27B1
      mutants R458K and R458Q and revealed their enzymatic properties. Substrate
      induced difference spectra and K(m) values for 1alpha-hydroxylation of 25(OH)D3
      indicate that the replacement of Arg458 with Lys or Gln does not affect substrate
      binding. However, these mutants showed remarkable decreases of both kcat values
      and the ratio of product formation to NADPH oxidation (coupling efficiency). A
      high K(m) value of R458Q for ADX concentration and a decrease of rate constant of
      the first electron transfer seem reasonable considering that the conversion from
      Arg to noncharged Gln abolishes salt-bridge formation with the acidic residue of
      ADX. On the other hand, R458K showed atypical kinetics for ADX concentration with
      Hill's constant of 2.0 and high catalytic activity at high ADX concentration by
      increase of coupling efficiency. These results suggest that conformational change
      of R458K by binding the two ADX molecules is essential for 1alpha-hydroxylation
      of 25(OH)D3. On the other hand, binding one ADX molecule is sufficient for the
      conformational change of the wild-type CYP27B1, judging from its Michaelis-Menten
      type kinetics for ADX concentration with high coupling efficiency. These results
      suggest that ADX functions as an effector for the oxygen transfer reaction in
      addition to being an electron donor for CYP27B1.

PMID- 16584178
TI  - Redox-dependent structural changes in the Azotobacter vinelandii
      bacterioferritin: new insights into the ferroxidase and iron transport mechanism.
AB  - In this work, we report the X-ray crystal structure of the aerobically isolated
      (oxidized) and the anaerobic dithionite-reduced (at pH 8.0) forms of the native
      Azotobacter vinelandii bacterioferritin to 2.7 and 2.0 A resolution,
      respectively. Iron K-edge multiple anomalous dispersion (MAD) experiments
      unequivocally identified the presence of three independent iron-containing sites
      within the protein structure. Specifically, a dinuclear (ferroxidase) site, a b
      type heme site, and the binding of a single iron atom at the four-fold molecular
      axis of the protein shell were observed. In addition to the novel observation of
      iron at the four-fold pore, these data also reveal that the oxidized form of the
      protein has a symmetrical ferroxidase site containing two five-coordinate iron
      atoms. Each iron atom is ligated by four carboxylate oxygen atoms and a single
      histidyl nitrogen atom. A single water molecule is found within hydrogen bonding
      distance of the ferroxidase site that bridges the two iron atoms on the side
      opposite the histidine ligands. Chemical reduction of the protein under anaerobic
      conditions results in an increase in the average Fe-Fe distance in the
      ferroxidase site from approximately 3.5 to approximately 4.0 A and the loss of
      one of the ligands, H130. In addition, there is significant movement of the
      bridging water molecule and several other amino acid side chains in the vicinity
      of the ferroxidase site and along the D helix to the three-fold symmetry axis. In
      contrast to previous work, the higher-resolution data for the dithionite-reduced
      structure suggest that the heme may be bound in multiple conformations. Taken
      together, these data allow a molecular movie of the ferroxidase gating mechanism
      to be developed and provide further insight into the iron uptake and/or release
      and mineralization mechanism of bacterioferritins in general.

PMID- 16584179
TI  - Catalyzed decomposition of urea. Molecular dynamics simulations of the binding of
      urea to urease.
AB  - We present the results of molecular dynamics simulations on the urea/urease
      system. The starting structure was prepared from the 2.0 A crystal structure of
      Benini et al. [(1999) Struct. Folding Des. 7, 205-216] of DAP-inhibited urease
      (PDB code ), and the trimeric structure (2479 residues) resulted in 180K atoms
      after solvation by water. The force field parameters were derived using the
      bonded model approach described by Hoops et al. [(1991) J. Am. Chem. Soc. 113,
      8262-8270]. Three different systems were analyzed, each one modeling a different
      protonation pattern for the His320 and His219 residues. In each case, the three
      monomers of urease have been analyzed separately. The time-averaged structures
      observed in the three monomers suggest that urease could follow two different
      competitive mechanisms. A "protein-assisted proton transfer" mechanism points to
      Asp221 as crucial for catalysis. An "Asp-mediated proton transfer" involves the
      transfer of a proton from the bridging OH to an NH2 moiety of urea, assisted by
      Asp360 in the active site. The impact of the simulation results on our
      understanding of urease catalysis is discussed in detail.

PMID- 16584180
TI  - Kinetic characterization of recombinant human acidic mammalian chitinase.
AB  - Human acidic mammalian chitinase (AMCase), a member of the family 18 glycosyl
      hydrolases, is one of the important proteins involved in Th2-mediated
      inflammation and has been implicated in asthma and allergic diseases. Inhibition
      of AMCase results in decreased airway inflammation and airway hyper
      responsiveness in a mouse asthma model, suggesting that the AMCase activity is a
      part of the mechanism of Th2 cytokine-driven inflammatory response in asthma. In
      this paper, we report the first detailed kinetic characterization of recombinant
      human AMCase. In contrast with mouse AMCase that has been reported to have a
      major pH optimum at 2 and a secondary pH optimum around 3-6, human AMCase has
      only one pH optimum for k(cat)/K(m) between pH 4 and 5. Steady state kinetics
      shows that human AMCase has "low" intrinsic transglycosidase activity, which
      leads to the observation of apparent substrate inhibition. This slow
      transglycosylation may provide a mechanism in vivo for feedback regulation of the
      chitinase activity of human AMCase. HPLC characterization of cleavage of
      chitooligosaccharides (4-6-mers) suggests that human AMCase prefers the beta
      anomer of chitooligosaccharides as substrate. Human AMCase also appears to cleave
      chitooligosaccharides from the nonreducing end primarily by disaccharide units.
      Ionic strength modulates the enzymatic activity and substrate cleavage pattern of
      human AMCase against fluorogenic substrates, chitobiose-4-methylumbelliferyl and
      chitotriose-4-methylumbelliferyl, and enhances activity against
      chitooligosaccharides. The physiological implications of these results are
      discussed.

PMID- 16584181
TI  - Evolution of enzymatic activities in the enolase superfamily: N-succinylamino
      acid racemase and a new pathway for the irreversible conversion of D- to L-amino
      acids.
AB  - Members of the mechanistically diverse enolase superfamily catalyze reactions
      that are initiated by abstraction of the alpha-proton of a carboxylate anion to
      generate an enolate anion intermediate that is stabilized by coordination to a
      Mg2+ ion. The catalytic groups, ligands for an essential Mg2+ and acid/base
      catalysts, are located in the (beta/alpha)8-barrel domain of the bidomain
      proteins. The assigned physiological functions in the muconate lactonizing enzyme
      (MLE) subgroup (Lys acid/base catalysts at the ends of the second and sixth beta
      strands in the barrel domain) are cycloisomerization (MLE), dehydration (o
      succinylbenzoate synthase; OSBS), and epimerization (L-Ala-D/L-Glu epimerase). We
      previously studied a putatively promiscuous member of the MLE subgroup with
      uncertain physiological function from Amycolatopsis that was discovered based on
      its ability to catalyze the racemization of N-acylamino acids (N-acylamino acid
      racemase; NAAAR) but also catalyzes the OSBS reaction [OSBS/NAAAR; Palmer, D. R.,
      Garrett, J. B., Sharma, V., Meganathan, R., Babbitt, P. C., and Gerlt, J. A.
      (1999) Biochemistry 38, 4252-4258]. In this manuscript, we report functional
      characterization of a homologue of this protein encoded by the genome of
      Geobacillus kaustophilus as well as two other proteins that are encoded by the
      same operon, a divergent member of the Gcn5-related N-acetyltransferase (GNAT)
      superfamily of enzymes whose members catalyze the transfer an acyl group from an
      acyl-CoA donor to an amine acceptor, and a member of the M20
      peptidase/carboxypeptidase G2 family. We determined that the member of the GNAT
      superfamily is succinyl-CoA:D-amino acid N-succinyltransferase, the member of the
      enolase superfamily is N-succinylamino acid racemase (NSAR), and the member of
      the M20 peptidase/carboxypeptidase G2 family is N-succinyl-L-amino acid
      hydrolase. We conclude that (1) these enzymes constitute a novel, irreversible
      pathway for the conversion of D- to L-amino acids and (2) the NSAR reaction is a
      new physiological function in the MLE subgroup. The NSAR is also functionally
      promiscuous and catalyzes an efficient OSBS reaction; intriguingly, the operon
      for menaquinone biosynthesis in G. kaustophilus does not encode an OSBS, raising
      the possibility that the NSAR is a bifunctional enzyme rather than an
      accidentally promiscuous enzyme.

PMID- 16584182
TI  - Coiled coils at the edge of configurational heterogeneity. Structural analyses of
      parallel and antiparallel homotetrameric coiled coils reveal configurational
      sensitivity to a single solvent-exposed amino acid substitution.
AB  - A detailed understanding of the mechanisms by which particular amino acid
      sequences can give rise to more than one folded structure, such as for proteins
      that undergo large conformational changes or misfolding, is a long-standing
      objective of protein chemistry. Here, we describe the crystal structures of a
      single coiled-coil peptide in distinct parallel and antiparallel tetrameric
      configurations and further describe the parallel or antiparallel crystal
      structures of several related peptide sequences; the antiparallel tetrameric
      assemblies represent the first crystal structures of GCN4-derived peptides
      exhibiting such a configuration. Intriguingly, substitution of a single solvent
      exposed residue enabled the parallel coiled-coil tetramer GCN4-pLI to populate
      the antiparallel configuration, suggesting that the two configurations are close
      enough in energy for subtle sequence changes to have important structural
      consequences. We present a structural analysis of the small changes to the helix
      register and side-chain conformations that accommodate the two configurations and
      have supplemented these results using solution studies and a molecular dynamics
      energetic analysis using a replica exchange methodology. Considering the previous
      examples of structural nonspecificity in coiled-coil peptides, the findings
      reported here not only emphasize the predisposition of the coiled-coil motif to
      adopt multiple configurations but also call attention to the associated risk that
      observed crytstal structures may not represent the only (or even the major)
      species present in solution.

PMID- 16584184
TI  - Transfer RNAs: electrostatic patterns and an early stage of recognition by
      synthetases and elongation factor EF-Tu.
AB  - Distributions of phosphate backbone-produced electrostatic potentials around
      several tRNAs were calculated by solving the nonlinear Poisson-Boltzmann
      equation. The tRNAs were either free or bound to the proteins involved in
      translation: aminoacyl-tRNA and elongation factor EF-Tu. We identified several
      regions of strong negative potential related to typical structural patterns of
      tRNA and invariant throughout the tRNAs. The patterns are conserved upon binding
      of tRNAs to the synthetase and the EF-Tu. Variation of tRNA charge in our
      theoretical calculations of electrostatic potential-mediated pK shifts of pH
      dependent labels attached to tRNA, compared to experimentally observed pK shifts
      for those labels, shows that the total charge of tRNA is large, within the
      interval of -40 to -70 proton charges. The electrostatic field of tRNA is
      sufficient to cause ionization of histidine residues of ARSase, causing
      additional free energy of ARSase-tRNA interaction of at least several kcal/mol.
      This may discriminate proteins with respect to the particular tRNA at large
      distances. Two types of tRNA-protein electrostatic recognition mechanisms are
      discussed. One, more specific, involves charges induced on protein by the large
      electrostatic potential of tRNA, while the other, less specific, does not involve
      induced charges.

PMID- 16584183
TI  - The Caenorhabditis elegans muscle specific serpin, SRP-3, neutralizes
      chymotrypsin-like serine peptidases.
AB  - Members of the intracellular serpin family may help regulate apoptosis, tumor
      progression, and metastasis. However, their in vivo functions in the context of a
      whole organism have not been easily defined. To better understand the biology of
      these serpins, we initiated a comparative genomics study using Caenorhabditis
      elegans as a model organism. Previous in silico analysis suggested that the C.
      elegans genome harbors nine serpin-like sequences bearing significant
      similarities to the human clade B intracellular serpins. However, only five genes
      appear to encode full-length serpins with intact reactive site loops. To
      determine if this was the case, we have cloned and expressed a putative
      inhibitory-type C. elegans serpin, srp-3. Analysis of SRP-3 inhibitory activity
      indicated that SRP-3 was a potent inhibitor of the serine peptidases,
      chymotrypsin and cathepsin G. Spatial and temporal expression studies using GFP
      and LacZ promoter fusions indicated that SRP-3 was expressed primarily in the
      anterior body wall muscles, suggesting that it may play a role in muscle cell
      homeostasis. Combined with previous studies showing that SRP-2 is an inhibitor of
      the serine peptidase, granzyme B, and lysosomal cysteine peptidases, these data
      suggested that C. elegans expressed at least two inhibitory-type serpins with
      nonoverlapping expression and inhibitory profiles. Moreover, the profiles of
      these clade L serpins in C. elegans share significant similarities with the
      profiles of clade B intracellular serpin members in higher vertebrates. This
      degree of conservation suggests that C. elegans should prove to be a valuable
      resource in the study of metazoan intracellular serpin function.

PMID- 16584185
TI  - Structural requirements for proinflammatory activity of porin P2 Loop 7 from
      Haemophilus influenzae.
AB  - Haemophilus influenzae type b (Hib) is one of the leading causes of invasive
      bacterial infection in young children, characterized by inflammation mainly
      mediated by cytokines and chemokines. One of the most abundant components of the
      Hib outer membrane is the P2 porin, which has been shown to induce the release of
      several inflammatory cytokines. Synthetic peptides corresponding to loops L5, L6,
      and L7 activate JNK and p38 mitogen-activated protein kinase (MAPK) pathways, L7
      being the most active peptide. Therefore, sequence-activity relationships and key
      residues were identified by elongating sequence to different extents, designing
      cyclic peptides, and performing an alanine scan of L7. The ability of mutant
      peptides to induce activation of signal transduction pathways and release of TNF
      alpha and IL-6 has been determined, and, in conjunction with CD spectra,
      bioinformatics analysis, and molecular dynamics data, showed that 6 out of 8
      amino acids contribute significantly to the overall activity. Molecular dynamics
      showed that L7 modifications increased loop rigidity and helicity after Gly6
      mutation, thus, providing a possible structural explanation for observed loss of
      bioactivity. This work provides insights into essential molecular details of P2
      that may impact on the pathogenesis of Hib infections where interruption of the
      signaling cascade could represent an attractive therapeutic strategy.

PMID- 16584186
TI  - Conformationally selective binding of nucleotide analogues to Escherichia coli
      RecA: a ligand-based analysis of the RecA ATP binding site.
AB  - The roles of the RecA protein in the survival of bacteria and the evolution of
      resistance to antibiotics make it an attractive target for inhibition by small
      molecules. The activity of RecA is dependent on the formation of a nucleoprotein
      filament on single-stranded DNA that hydrolyzes ATP. We probed the nucleotide
      binding site of the active RecA protein using modified nucleotide triphosphates
      to discern key structural elements of the nucleotide and of the binding site that
      result in the activation of RecA for NTP hydrolysis. Our results show that the
      RecA-catalyzed hydrolysis of a given nucleotide triphosphate or analogue thereof
      is exquisitely sensitive to certain structural elements of both the base and
      ribose moieties. Furthermore, our ligand-based approach to probing the RecA ATP
      binding site indicated that the binding of nucleotides by RecA was found to be
      conformationally selective. Using a binding screen that can be readily adapted to
      high-throughput techniques, we were able to segregate nucleotides that interact
      with RecA into two classes: (1) NTPs that preferentially bind the active
      nucleoprotein filament conformation and either serve as substrates for or
      competitively inhibit hydrolysis and (2) nonsubstrate NTPs that preferentially
      bind the inactive RecA conformation and facilitate dissociation of the RecA-DNA
      species. These results are discussed in the context of a recent structural model
      for the active RecA nucleoprotein filament and provide us with important
      information for the design of potent, conformationally selective modulators of
      RecA activities.

PMID- 16584187
TI  - Intersubunit electrostatic complementarity in the RecA nucleoprotein filament
      regulates nucleotide substrate specificity and conformational activation.
AB  - The Escherichia coli RecA protein is the prototypical member of a family of
      molecular motors that transduces ATP binding and hydrolysis for mechanical
      function. While many general mechanistic features of RecA action are known,
      specific structural and functional insights into the molecular basis of RecA
      activation remain elusive. Toward a more complete understanding of the
      interdependence between ATP and DNA binding by RecA, we report the
      characterization of a mutant RecA protein wherein the aspartate residue at
      position 100 within the ATP binding site is replaced by arginine.
      Physiologically, D100R RecA was characterized by an inducible, albeit reduced,
      activation of the SOS response and a diminished ability to promote cellular
      survival after UV irradiation. Biochemically, the D100R substitution caused a
      surprisingly modest perturbation of RecA-ATP interactions and an unexpected and
      significant decrease in the affinity of RecA for ssDNA. Moreover, in vitro assays
      of RecA activities requiring the coordinated processing of ATP and DNA revealed
      (1) a 2-5-fold decrease in steady-state turnover of ATP; (2) no formation of
      mixed nucleoprotein filaments when wild-type and D100R RecA compete for limiting
      ssDNA; and (3) no formation of strand exchange reaction products. Taken together,
      these results suggest that the D100R mutational effects on isolated RecA
      activities combine synergistically to perturb its higher-order functions. We
      conclude that the replacement of Asp100 resulted in a change in the electrostatic
      complementarity between RecA monomers during active filament assembly that
      prevents the protein from fully accessing the active multimeric state.

PMID- 16584188
TI  - D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol alters cellular
      cholesterol homeostasis by modulating the endosome lipid domains.
AB  - D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) is a frequently
      used inhibitor of glycosphingolipid biosynthesis. However, some interesting
      characteristics of D-PDMP cannot be explained by the inhibition of glycolipid
      synthesis alone. In the present study, we showed that d-PDMP inhibits the
      activation of lysosomal acid lipase by late endosome/lysosome specific lipid,
      bis(monoacylglycero)phosphate (also called as lysobisphosphatidic acid), through
      alteration of membrane structure of the lipid. When added to cultured
      fibroblasts, D-PDMP inhibits the degradation of low-density lipoprotein (LDL) and
      thus accumulates both cholesterol ester and free cholesterol in late
      endosomes/lysosomes. This accumulation results in the inhibition of LDL-derived
      cholesterol esterification and the decrease of cell surface cholesterol. We
      showed that D-PDMP alters cellular cholesterol homeostasis in a glycosphingolipid
      independent manner using L-PDMP, a stereoisomer of D-PDMP, which does not inhibit
      glycosphingolipid synthesis, and mutant melanoma cell which is defective in
      glycolipid synthesis. Altering cholesterol homeostasis by D-PDMP explains the
      unique characteristics of sensitizing multidrug resistant cells by this drug.

PMID- 16584189
TI  - Interaction of the intrinsically unstructured phage lambda N Protein with
      Escherichia coli NusA.
AB  - N protein of the Escherichia coli phage lambda (lambdaN) is involved in
      antitermination, a transcription regulatory process that is essential for the
      expression of delayed early genes during phage lytic development. lambdaN is an
      intrinsically unstructured protein that possesses three distinct binding sites
      interacting with the carboxy terminus of the E. coli host factor protein NusA,
      the viral nutBoxB-RNA, and RNA polymerase, respectively. Heteronuclear NMR
      experiments with lambdaN(1-53) in complex with NusA(339-495) revealed that upon
      complex formation the lambdaN-binding interface, lambdaN(34-47), adopts a rigid
      structure. NMR data also indicate the induction of a weak helical structure in
      the nutboxB RNA-binding region lambdaN(1-22) upon binding to NusA(339-495) even
      in the absence of RNA. Titration experiments of the lambdaN(1-53)-nutBoxB RNA
      complex with NusA(339-495) revealed that the ternary complex can be described in
      terms of two structurally independent binary interactions. Furthermore, chemical
      shift perturbation experiments with different NusA constructs and different
      lambdaN peptides showed that only NusA(353-416) is involved in lambdaN binding.
      We found that only one molecule of NusA(339-426) binds to one molecule of
      lambdaN(1-53). We also clarified the role of the lambdaN-binding region and could
      show that N41-R47 also binds to NusA(339-495). Furthermore, we observe that
      lambdaN(1-22) adopts a helical fold upon binding to NusA(339-495), in agreement
      with one of the theoretical models of lambdaN action.

PMID- 16584190
TI  - Structure of the eukaryotic initiation factor (eIF) 5 reveals a fold common to
      several translation factors.
AB  - Eukaryotic initiation factor 5 (eIF5) plays multiple roles in translation
      initiation. Its N-terminal domain functions as a GTPase-activator protein (GAP)
      for GTP bound to eIF2, while its C-terminal region nucleates the interactions
      between multiple translation factors, including eIF1, which acts to inhibit GTP
      hydrolysis or P(i) release, and the beta subunit of eIF2. These proteins and the
      events in which they participate are critical for the accurate recognition of the
      correct start codon during translation initiation. Here, we report the three
      dimensional solution structure of the N-terminal domain of human eIF5, comprising
      two subdomains, both reminiscent of nucleic-acid-binding modules. The N-terminal
      subdomain contains the "arginine finger" motif that is essential for GAP function
      but which, unusually, resides in a partially disordered region of the molecule.
      This implies that a conformational reordering of this portion of eIF5 is likely
      to occur upon formation of a competent complex for GTP hydrolysis, following the
      appropriate activation signal. Interestingly, the N-terminal subdomain of eIF5
      reveals an alpha/beta fold structurally similar to both the archaeal orthologue
      of the beta subunit of eIF2 and, unexpectedly, to eIF1. These results reveal a
      novel protein fold common to several factors involved in related steps of
      translation initiation. The implications of these observations are discussed in
      terms of the mechanism of translation initiation.

PMID- 16584191
TI  - Streptococcal M protein: structural studies of the hypervariable region, free and
      bound to human C4BP.
AB  - Streptococcus pyogenes is a Gram-positive bacterium that causes several diseases,
      including acute tonsillitis and toxic shock syndrome. The surface-localized M
      protein, which is the most extensively studied virulence factor of S. pyogenes,
      has an approximately 50-residue N-terminal hypervariable region (HVR) that plays
      a key role in the escape of the host immunity. Despite the extensive sequence
      variability in this region, many HVRs specifically bind human C4b-binding protein
      (C4BP), a plasma protein that inhibits complement activation. Although the more
      conserved parts of M protein are known to have dimeric coiled-coil structure, it
      is unclear whether the HVR also is a coiled coil. Here, we use nuclear magnetic
      resonance (NMR) to study the conformational properties of HVRs from M4 and M22
      proteins in isolation and in complex with the M protein binding portion of C4BP.
      We conclude that the HVRs of M4 and M22 are folded as coiled coils and that the
      folded nucleus of the M4 HVR has a length of approximately 27 residues. Moreover,
      we demonstrate that the C4BP binding surface of M4-N is found within a region of
      four heptad repeats. Using molecular modeling, we propose a model for the
      structure of the M4 HVR that is consistent with our experimental information from
      NMR spectroscopy.

PMID- 16584193
TI  - Backbone NMR assignments and H/D exchange studies on the ferric azide- and
      cyanide-inhibited forms of Pseudomonas aeruginosa heme oxygenase.
AB  - The 198 amino acid long heme oxygenase from Pseudomonas aeruginosa (pa-HO) was
      studied by multinuclear and multidimensional NMR spectroscopy in its paramagnetic
      cyanide-inhibited (pa-HO-CN) and azide-inhibited (pa-HO-N3) forms. Nearly
      complete backbone assignments (>93%) of all non-proline residues have been
      obtained, with the majority of the nonassigned residues corresponding to the
      first 10 amino terminal residues. Resonances strongly affected by heme iron
      paramagnetism were assigned with the aid of selective amino acid labeling and
      experiments tailored to detect fast relaxing signals, whereas the rest of the
      polypeptide was assigned using conventional three-dimensional NMR experiments.
      Amide chemical shift assignments were used to monitor the rate of exchange of
      backbone protons in hydrogen-deuterium exchange experiments. The polypeptide in
      the pa-HO-N3 complex was found to be significantly less prone to exchange than
      the polypeptide in pa-HO-CN, which we interpret to indicate that pa-HO-N3 is
      conformationally less flexible than pa-HO-CN. The differences in protection
      factors extend to regions of the protein remote from the heme iron and distal
      ligand. Mapping the differences in protection factors into the X-ray crystal
      structure of pa-HO [Friedman, J., Lad, L., Li, H., Wilks, A. Poulos, T. L. (2004)
      Biochemistry 43, 5239-5345] suggests that the distinct chemical properties
      imparted by the coordination of azide or cyanide to the heme iron [Zeng, Y.
      Caignan, G. A., Bunce, R. A., Rodriguez, J. C., Wilks, A., Rivera, M. (2005) J.
      Am. Chem. Soc. 127, 9794-9807] are transmitted to the polypeptide by a network of
      structural water molecules extending from the active site to the surface of the
      enzyme. Finally, while the 1H amide resonance of Gly125 was too broad to detect,
      the corresponding 15N resonance exhibits a large downfield shift, large line
      width, steep temperature dependence, and a larger than usual upfield deuterium
      isotope effect. These properties indicate unpaired spin delocalization from the
      heme iron into the Gly 15N atom via formation of a hydrogen bond between the
      coordinated azide nitrogen and the Gly125 N-H.

PMID- 16584192
TI  - Effect of site-directed mutagenesis of methylglyoxal-modifiable arginine residues
      on the structure and chaperone function of human alphaA-crystallin.
AB  - We reported previously that chemical modification of human alphaA-crystallin by a
      metabolic dicarbonyl compound, methylglyoxal (MGO), enhances its chaperone-like
      function, a phenomenon which we attributed to formation of argpyrimidine at
      arginine residues (R) 21, 49, and 103. This structural change removes the
      positive charge on the arginine residues. To explore this mechanism further, we
      replaced these three R residues with a neutral alanine (A) residue one at a time
      or in combination and examined the impact on the structure and chaperone
      function. Measurement of intrinsic tryptophan fluorescence and near-UV CD spectra
      revealed alteration of the microenvironment of aromatic amino acid residues in
      mutant proteins. When compared to wild-type (wt) alphaA-crystallin, the chaperone
      function of R21A and R103A mutants increased 20% and 18% as measured by the
      insulin aggregation assay and increased it as much as 39% and 28% when measured
      by the citrate synthase (CS) aggregation assay. While the R49A mutant lost most
      of its chaperone function, R21A/R103A and R21A/R49A/R103A mutants had slightly
      better function (6-14% and 10-14%) than the wt protein in these assays. R21A and
      R103A mutants had higher surface hydrophobicity than wt alphaA-crystallin, but
      the R49A mutant had lower hydrophobicity. R21A and R103A mutants, but not the
      R49A mutant, were more efficient than wt protein in refolding guanidine
      hydrochloride-treated malate dehydrogenase to its native state. Our findings
      indicate that the positive charges on R21, R49, and R103 are important
      determinants of the chaperone function of alphaA-crystallin and suggest that
      chemical modification of arginine residues may play a role in protein aggregation
      during lens aging and cataract formation.

PMID- 16584194
TI  - Conformation of the cell division regulator MinE: evidence for interactions
      between the topological specificity and anti-MinCD domains.
AB  - Symmetric division of Gram-negative bacteria depends on the combined action of
      three proteins that ensure correct positioning of the cell division septum,
      namely, MinC, MinD, and MinE. To achieve this function, MinC and MinD form a
      membrane-bound complex that blocks cell division at all potential sites. Opposing
      this inhibition is MinE, which interacts with MinD via its N-terminal anti-MinCD
      domain to site-specifically counter the action of the MinCD complex. The anti
      MinCD domain has been proposed to bind MinD in a helical conformation; however,
      little is actually known about the structure of this functionally critical
      region. To understand how MinE can perform its anti-MinCD function, we have
      therefore investigated the conformation of the full-length MinE from Neisseria
      gonorrhoeae by solution NMR. Although solubility considerations required the use
      of sample conditions that limit the observation of amide resonances to regions
      that are protected from solvent exchange, backbone chemical shifts from both N-
      and C-terminal domains could be assigned. In contrast to previous models,
      secondary chemical shift analysis of these solvent-protected regions shows that
      parts of the N-terminal anti-MinCD domain are stably folded with many
      functionally important residues localizing to a beta-structure. In addition, this
      N-terminal domain may be interacting with the C-terminal topological specificity
      domain, since mutations made in one domain led to NMR spectral changes in both
      domains. The nonfunctional MinE mutant L22D showed even larger evidence of
      structural perturbations in both domains, with significant destabilization of the
      entire MinE structure. Overall, these results suggest that there is an intimate
      structural association between the anti-MinCD and topological specificity
      domains, allowing the functional properties of the two domains to be modulated
      through this interaction.

PMID- 16584195
TI  - Single-turnover kinetic experiments confirm the existence of high- and low
      affinity ATPase sites in Escherichia coli Lon protease.
AB  - Lon is an ATP-dependent serine protease that degrades damaged and certain
      regulatory proteins in vivo. Lon exists as a homo-oligomer and represents one of
      the simplest ATP-dependent proteases because both the protease and ATPase domains
      are located within each monomeric subunit. Previous pre-steady-state kinetic
      studies revealed functional nonequivalency in the ATPase activity of the enzyme
      [Vineyard, D., et al. (2005) Biochemistry 44, 1671-1682]. Both a high- and low
      affinity ATPase site has been previously reported for Lon [Menon, A. S., and
      Goldberg, A. L. (1987) J. Biol. Chem. 262, 14921-14928]. Because of the differing
      affinities for ATP, we were able to monitor the activities of the sites
      separately and determine that they were noninteracting. The high-affinity sites
      hydrolyze ATP very slowly (k(obs) = 0.019 +/- 0.002 s(-1)), while the low
      affinity sites hydrolyze ATP quickly at a rate of 17.2 +/- 0.09 s(-1), which is
      comparable to the previously observed burst rate. Although the high-affinity
      sites hydrolyze ATP slowly, they support multiple rounds of peptide hydrolysis,
      indicating that ATP and peptide hydrolysis are not stoichiometrically linked.
      However, ATP binding and hydrolysis at both the high- and low-affinity sites are
      necessary for optimal peptide cleavage and the stabilization of the
      conformational change associated with nucleotide binding.

PMID- 16584196
TI  - Mutation of asparagine 52 to glycine promotes the alkaline form of iso-1
      cytochrome c and causes loss of cooperativity in acid unfolding.
AB  - The kinetics and thermodynamics of the alkaline and acid conformational
      transitions of a Lys 79 --> Ala/Asn 52 --> Gly (A79G52) variant of iso-1
      cytochrome c are studied. The Lys 79 --> Ala mutation is designed to limit heme
      ligation in the alkaline conformer to Lys 73. The Asn 52 --> Gly mutation is
      intended to shift the population of the alkaline conformer to physiological pH
      based on the hierarchical nature of the cooperative substructures of this
      protein. The midpoint pH for formation of the alkaline conformer is approximately
      7.45. The kinetics for the alkaline conformational transition of the A79G52
      variant are consistent with the ionization constant, pK(H), for the trigger group
      controlling formation of the alkaline conformer being approximately 9.5. This
      pK(H) is low for alkaline conformers involving lysine-heme ligation but is
      consistent with the pK(a) of the highest of three ionizable groups which modulate
      formation of the histidine-heme alkaline conformer of a His 73 variant of iso-1
      cytochrome c [Martinez, R. E., and Bowler, B. E. (2004) J. Am. Chem. Soc. 126,
      6751-6758]. The acid transition of the A79G52 variant is split into two phases.
      Both the Lys 79 --> Ala and Asn 52 --> Gly mutations are expected to affect the
      buried hydrogen bond network of cytochrome c, suggesting that this network is an
      important modulator of the acid unfolding of cytochrome c.

PMID- 16584197
TI  - Effects of salt on the thermal stability of human plasma high-density
      lipoprotein.
AB  - High-density lipoproteins (HDL) mediate cholesterol removal and thereby protect
      against atherosclerosis. Mature spherical HDL contain the apolar lipid core and
      polar surface of proteins and phospholipids. Earlier, we showed that the
      structural integrity of HDL is modulated by kinetic barriers that prevent
      spontaneous protein dissociation and lipoprotein fusion and rupture. To determine
      the role of electrostatic interactions in the kinetic stability of mature HDL,
      here we analyze the effects of salt and pH on their thermal denaturation. In low
      salt buffer at pH 5.7-7.7, HDL are highly thermostable. Increasing the salt
      concentration from 0 to 0.3 M NaCl causes low-temperature shifts in the
      calorimetric HDL transitions of up to -14 degrees C. This salt-induced
      destabilization leads to protein unfolding below 100 degrees C, facilitating the
      first Arrhenius analysis of HDL denaturation by circular dichroism spectroscopy.
      In 150 mM NaCl, two kinetic phases in HDL protein unfolding are observed: a
      faster phase with an activation energy E(a,fast) < or =15 kcal/mol and a slower
      phase with an E(a,slow) = 50 +/- 7 kcal/mol. Gel electrophoresis and electron
      microscopic data suggest that the faster phase involves partial protein unfolding
      but no significant protein dissociation or changes in HDL size, while the slower
      phase involves complete protein unfolding, partial protein dissociation, and HDL
      fusion. Hence, the slower phase may resemble HDL remodeling and fusion by plasma
      enzymes during metabolism. Analysis of the effects of various salts, sucrose, and
      pH suggests that HDL destabilization by salt results from ionic screening of
      favorable short-range electrostatic interactions such as salt bridges.
      Consequently, electrostatic interactions significantly contribute to the high
      thermostability of HDL in low-salt solutions.

PMID- 16584198
TI  - Identification of membrane-contacting loops of the catalytic domain of cytochrome
      P450 2C2 by tryptophan fluorescence scanning.
AB  - The catalytic domain of cytochrome P450 is thought to contact the lipid core of
      the endoplasmic reticulum membrane based on antibody epitope accessibility,
      protease susceptibility, and hydrophobic surfaces present on P450 structures of
      solubilized forms of the proteins. Quenching by nitroxide spin label-modified
      phospholipids of the fluorescence of tryptophan residues substituted into
      cytochrome P450 2C2, modified to contain tryptophan only at position 120, was
      used to identify regions of P450 inserted into the lipid core and to estimate the
      depth of penetration. Consistent with the proposed models of cytochrome P450
      membrane interaction, the fluorescence of tryptophans inserted at residues 36 and
      69 in the two segments of P450 2C2 flanking the A-helix and at residue 380 in the
      beta2-2 strand was quenched by nitroxide spin labels on carbon 5 of the fatty
      acid tails of the phospholipids within the lipid bilayer. The fluorescence of
      tryptophan at 380 was also strongly quenched by a spin label on carbon 12 of the
      fatty acids suggesting it was deepest in the membrane. However, fluorescence of
      tryptophan substituted at residue 225 in the F-G loop, which was predicted to be
      in the lipid bilayer, was not quenched by the spin labels at carbons 5 and 12 of
      the fatty acids. The pattern of quenching of fluorescence for tryptophans at the
      other positions tested, 80, 189, 239, and 347, was similar to the parent protein
      indicating they were not inserted into the lipid bilayer as expected. The results
      are consistent with an orientation of cytochrome P450 2C2 in the membrane in
      which positions 36, 69, and 380 are inserted into the lipid bilayer and residues
      80 and 225 are near or within the phospholipid headgroup region. In this
      orientation, the F-G loop, which contains residue 225, could form a dimerization
      interface as was observed in the P450 2C8 crystal structure (Schoch, G. A., et
      al. (2004) J. Biol. Chem. 279, 9497).

PMID- 16584199
TI  - Prediction of nucleating sequences from amyloidogenic propensities of tau-related
      peptides.
AB  - Physical properties, including amyloid morphology, FTIR and CD spectra,
      enhancement of Congo red absorbance, polymerization rate, critical monomer
      concentration, free energy of stabilization, hydrophobicity, and the partition
      coefficient between soluble and amyloid states, were measured for the tau-related
      peptide Ac-VQIVYK amide (AcPHF6) and its single site mutants Ac-VQIVXK amide (X
      not equal Cys). Transmission electron microscopy showed that 15 out of the 19
      peptides formed amyloid in buffer, with morphologies ranging from straight and
      twisted filaments to sheets and rolled sheets. Using principal component analysis
      (PCA), measured properties were treated in a comprehensive manner, and scores
      along the most significant principal components were used to define individual
      amino acid amyloidogenic propensities. Quantitative structure-activity modeling
      (QSAM) showed that residues with greater size and hydrophobicity made the largest
      contributions to the propensity of peptides to form amyloid. Using individual
      amino acid propensities, sequences within tau with high amyloid-forming potential
      were estimated and found to include 226VAVVR230 in the proline-rich region,
      275VQIINK280 (PHF6) and 306VQIVYK311 (PHF6) within the microtubule binding
      region, and 392IVYK395 in the C-tail region of the protein. The results suggest
      that regions outside the microtubule-binding region may play important roles in
      tau aggregation kinetics or paired helical filament structure.

PMID- 16584200
TI  - A glutamine to glutamate mutation at position 170 (Q170E) in the rabbit
      Na+/glucose cotransporter, rSGLT1, enhances binding affinity for Na+.
AB  - Using cysteine mutagenesis and chemical modification by methanethiosulfonate
      derivatives, it was demonstrated that the external putative loop, joining
      transmembrane segments (TM's) IV-V of rabbit Na+/glucose cotransporter, rSGLT1,
      forms part of a Na+ binding and voltage sensing domain. Within this region,
      exposure to cationic (2-aminoethyl)methanethiosulfonate hydrobromide (MTSEA)
      inhibited F163C, A166C, and L173C, but anionic sodium (2
      sulfonatoethyl)methanethiosulfonate (MTSES) had no effect. Unexpectedly, MTSEA
      had no effect on Q170C; however, MTSES profoundly altered Q170C charge transfer
      and turnover, leaving Na+ and sugar binding affinity unchanged, but mutation of
      glutamine to anionic glutamate (Q170E) shifted V(0.5) to positive potentials,
      suggesting enhanced Na+ affinity. To clarify the role of glutamine 170 in Na+
      interaction, we embarked on a more detailed investigation of Q170E using the two
      microelectrode voltage clamping in Xenopus oocytes. Compared to wild-type (wt)
      rSGLT1, Q170E exhibits (i) a 2-fold decrease in methyl alpha-D-glucopyranoside
      affinity (-150 to -90 mV), (ii) a 5-fold increase in Na+ affinity (-150 to -100
      mV) with less voltage dependency, (iii) reduced Na+ leak, and (iv) two transient
      current decay constants (tau(fast), tau(slow)) compared to three (tau(fast),
      tau(medium), tau(slow)) for wt, and computer simulation of Q170E pre-steady-state
      currents with a four-state kinetic model yields parameters similar to wt SGLT1,
      except for a reduced Na+ debinding rate constant compared to wt. Taken together,
      the data strengthen the conclusion that residue 170 lies in the Na+ pathway and
      provide the first evidence that it participates in determining Na+ binding.

PMID- 16584201
TI  - ADP-ribosylation of cyclophilin A by Pseudomonas aeruginosa exoenzyme S.
AB  - The virulence of the opportunistic pathogen Pseudomonas aeruginosa (Pa) is in
      part mediated by the type III secretion (TTS) of bacterial proteins into
      eukaryotic hosts. Exoenzyme S (ExoS) is a bifunctional Pa TTS effector protein,
      with GTPase-activating (GAP) and ADP-ribosyltransferase (ADPRT) activities. Known
      cellular substrates of TTS-translocated ExoS (TTS-ExoS) ADPRT activity include
      proteins in the Ras superfamily and ERM family proteins. This study describes the
      ADP-ribosylation of a non-G-protein substrate of TTS-ExoS, cyclophilin A (CpA), a
      peptidyl-prolyl isomerase (PPIase). Four novel 17 kDa proteins (pI 6.5-6.8) were
      recognized in a proteomic screen of lysates of human epithelial cells that had
      been exposed to ExoS-producing Pa, but not an isogenic non-ExoS producing strain.
      The proteins were identified as isoforms of CpA using MALDI-TOF mass spectrometry
      and confirmed by Western blotting. Mutagenesis analysis identified arginine 55
      and 69 of CpA as sites of ExoS ADP-ribosylation. Examination of the effect of
      ExoS ADP-ribosylation on CpA function found a moderate (19%) decrease in prolyl
      isomerization of a Xaa-Pro containing peptides. In comparison, GST-CpA co
      immunoprecipitation studies found ExoS ADP-ribosylation of CpA to efficiently
      inhibit CpA binding to calcineurin/PP2B phosphatase. Our results support that
      ExoS ADP-ribosylates and affects the function of the cytosolic protein, CpA, with
      the predominant functional effect relating to interference of CpA-cellular
      protein interactions.

PMID- 16584202
TI  - A novel type carbohydrate-binding module identified in alpha-glucan, water
      dikinases is specific for regulated plastidial starch metabolism.
AB  - The phosphorylation of the amylopectin fraction of starch catalyzed by the alpha
      glucan, water dikinase (GWD, EC 2.7.9.4) plays a pivotal role in starch
      metabolism. Limited proteolysis of the potato tuber (Solanum tuberosum) GWD
      (StGWD, 155 kDa) by trypsin primarily produced stable fragments of 33 and 122
      kDa, termed the SBD fragment and N11, respectively, as generated by trypsin
      cleavage at Arg-286. SBD and N11 were generated using recombinant DNA technology
      and purified to near homogeneity. Tandem repeat sequences, SBD-1 and SBD-2, of a
      region that is significantly similar in sequence to N-terminal regions of
      plastidial alpha-amylases are located in the N-terminus of StGWD. The SBD-1 motif
      is located within the sequence of the SBD fragment, and our results demonstrate
      that the fragment composes a new and novel carbohydrate-binding module (CBM),
      apparently specific for plastidial alpha-glucan degradation. By mutational
      analyses of conserved Trp residues located within the SBD-1 motif, W62 and W117,
      we show that these aromatic residues are vital for carbohydrate binding. N11
      still possessed starch phosphorylating activity, but with a 2-fold higher
      specific activity compared to that of wild type (WT) StGWD using potato starch as
      the glucan substrate, whereas it had double the K(m) value for the same
      substrate. Furthermore, investigation of the chains phosphorylated by WT StGWD
      and N11 shows that N11 exhibits a higher preference for phosphorylating shorter
      chains of the amylopectin molecule as compared to WT. From analyses of the glucan
      substrate specificity, we found up to 5-fold higher specific activity for N11
      using amylose as the substrate.

PMID- 16584203
TI  - Relationship of stopped flow to steady state parameters in the dimeric copper
      amine oxidase from Hansenula polymorpha and the role of zinc in inhibiting
      activity at alternate copper-containing subunits.
AB  - The expression of a copper amine oxidase (CAO) from Hansenula polymorpha in
      Saccharomyces cerevisiae under differing culture conditions leads to the
      incorporation of varied levels of CAO-bound zinc. The presence of substantial
      amount of zinc results in two distinctive enzyme species, designated as the fast
      and slow enzymes. Both forms are rapidly reduced by substrate methylamine with a
      rate constant of 199 s(-1) but behave remarkably differently in their oxidation
      rates; the fast enzyme is oxidized by dioxygen at a rate of 22.1 s(-1), whereas
      the slow enzyme reacts at a rate of 1.8 x 10(-4) s(-1). The apparent kcat of the
      enzyme preparation is linearly proportional to the fraction of the fast enzyme,
      with an extrapolated value of 6.17 s(-1) when the enzyme is 100% in its "fast"
      form. A comparison of rate constants for cofactor reduction and reoxidation
      steps, measured in stopped flow experiments, to the extrapolated kcat implicates
      additional steps in the steady state reaction. Measurement of the proportion of
      oxidized (ETPQ(ox)) and reduced cofactor (ETPQ(red)) under steady state
      conditions indicates approximately 50% of each cofactor form at 0.8 or 2 mM
      methylamine. Kinetic isotope effect measurements using deuterated amine substrate
      lead to the following steady state values: (D)(k(red)) = 8.5 (0.5), (D)(kcat) =
      1.7 (0.1), and (D)(kcat/K(m)) = 4.3 (0.2). The collective data allow the
      calculation of partially rate-determining constants during the reductive half
      reaction (ca. 200 s(-1) for binding of substrate to ETPQ(ox) and 27.9 s(-1) for
      release of aldehyde product or a protein isomerization from ETPQ(red)); an
      additional step with a rate constant of 13.2 s(-1) is assigned to the oxidative
      half-reaction, most likely for the release of product hydrogen peroxide. These
      results, together with the sole detection of oxidized and reduced cofactor during
      rapid scanning stopped flow experiments, indicate that four steps contribute to
      kcat, with the first electron transfer from cofactor to O2 contributing ca. 29%.
      An investigation of the relationship between the copper content and the extent of
      the fast enzyme shows that only the copper-containing homodimer is capable of
      rapid reoxidation and that zinc-copper heterodimers are incapable of rapid
      turnover at either subunit. This implies communication between the metal sites of
      the two subunits per dimer that impacts O2 binding and/or electron transfer from
      reduced cofactor to bound O2.

PMID- 16584204
TI  - A unique molten globule state occurs during unfolding of cytochrome c by LiClO4
      near physiological pH and temperature: structural and thermodynamic
      characterization.
AB  - We have carried out denaturation studies of bovine cytochrome c (cyt c) by LiClO4
      at pH 6.0 and 25 degrees C by observing changes in difference molar absorbance at
      400 nm (Deltaepsilon400), mean residue ellipticities at 222 nm ([theta]222) and
      difference mean residue ellipticity at 409 nm (Delta[theta]409). The denaturation
      is a three-step process when measured by Deltaepsilon400 and Delta[theta]409, and
      it is a two-step process when monitored by [theta]222. The stable folding
      intermediate state has been characterized by near- and far-UV circular dichroism,
      tryptophan fluorescence, 8-anilino-1-naphthalene sulfonic acid (ANS) binding, and
      intrinsic viscosity measurements. A comparison of the conformational and
      thermodynamic properties of the LiClO4-induced molten globule (MG) state with
      those induced by other solvent conditions (e.g., low pH, LiCl, and CaCl2)
      suggests that LiClO4 induces a unique MG state, i.e., (i) the core in the LiClO4
      induced state retains less secondary and tertiary structure than that in the MG
      states obtained in other solvent conditions, and (ii) the thermodynamic stability
      associated with the LiClO4-induced process, native state <--> MG state, is the
      same as that observed for each transition between native and MG states induced by
      other solvent conditions.

PMID- 16584205
TI  - Epidermal growth factor mutant with wild-type affinity for both ErbB1 and ErbB3.
AB  - The family of epidermal growth factor (EGF)-like ligands binds to ErbB receptors
      in a highly selective manner. Previous studies indicated that both linear regions
      of the ligand play a major role in determining receptor selectivity, and phage
      display studies showed that each region could be optimized independently for
      enhanced affinity. In this study, we broadened the ErbB binding specificity of
      EGF by introducing the optimal sequence requirements for ErbB3 binding in both
      the N- and C-terminal linear regions. One such EGF mutant, designated
      WVR/EGF/IADIQ, gained high affinity for ErbB3 and showed concomitant ErbB3
      activation through ErbB2.ErbB3 heterodimers similar to the natural ErbB3 ligand
      NRG1beta, while the capacity to bind and activate ErbB1 was fully maintained.
      Despite its high affinity for ErbB1 and ErbB3, this mutant was unable to activate
      ErbB1.ErbB3 heterodimers, as shown by the cell survival and receptor
      phosphorylation analysis. We concluded that despite the fact that no naturally
      occurring ligand exists with this dual-specificity, high-affinity binding to both
      ErbB1 and ErbB3 is not mutually exclusive. This mutant can be useful in a direct
      structural comparison of the ligand-binding characteristics of ErbB1 and ErbB3.

PMID- 16584206
TI  - Fabrication of one-dimensional colloidal assemblies from electrospun nanofibers.
AB  - Electrospun nanofibers were used as confining geometries for fabricating 1-D
      colloidal assemblies. Silica particles dispersed in several different polymer
      solutions were cast into nanofibers by an electrospinning process. The silica
      particle configurations were examined in terms of the size ratio of silica
      particles to nanofibers and the properties of the dispersing medium. As the
      electrospun fiber was extended highly, the silica particles dispersed in the
      polymer solution began to assemble spontaneously into a pearl-necklace structure.
      We also demonstrated the alignment of 1-D silica assemblies using a designed
      configuration of collector electrodes.

PMID- 16584207
TI  - Block copolymer micelles as switchable templates for nanofabrication.
AB  - Block copolymer inverse micelles from polystyrene-block-poly-2-vinylpyridine (PS
      b-P2VP) deposited as monolayer films onto surfaces show responsive behavior and
      are reversibly switchable between two states of different topography and surface
      chemistry. The as-coated films are in the form of arrays of nanoscale bumps,
      which can be transformed into arrays of nanoscale holes by switching through
      exposure to methanol. The use of these micellar films to act as switchable etch
      masks for the structuring of the underlying material to form either pillars or
      holes depending on the switching state is demonstrated.

PMID- 16584208
TI  - Photolithographically patterned surface modification of poly(dimethylsiloxane)
      via UV-initiated graft polymerization of acrylates.
AB  - Patterned surface modification of poly(dimethylsiloxane) (PDMS) is achieved by
      combining ultraviolet-initiated graft polymerization (UV-GP) and
      photolithography. Poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA)
      patterns were grafted onto PDMS with micrometer-scale feature edge resolution.
      The morphology and chemical composition of the grafted layers were assessed by
      optical and atomic force microscopy (AFM), X-ray photoelectron spectroscopy
      (XPS), and XPS imaging. AFM section analyses demonstrated the deposition of 33 +/
      1 and 62 +/- 8 nm thick patterned films of PAA and PMAA, respectively. Spatially
      resolved C 1s XPS provided images of carboxylic acid functionalities, verifying
      the patterned deposition of acrylate films on PDMS. These observations
      demonstrate the general usefulness of UV-GP and photolithography for
      micropatterning.

PMID- 16584209
TI  - Selective recruitment of membrane protein complexes onto gold substrates
      patterned by dip-pen nanolithography.
AB  - Dip-pen nanolithography (DPN) is employed to develop a generic array platform for
      the selective recruitment of membrane protein complexes. An atomic force
      microscope tip inked with HS(CH2)16NH2 is used to generate amino-terminated
      domains on gold. These domains can be arranged into microscopic and
      submicroscopic patterns, and the untreated gold substrate is subsequently blocked
      with HS(CH2)2CONH(CH2CH2O)15CH3, a compound known to resist the unspecific
      binding of proteins and cells. The patterned gold substrate is exposed to an
      enriched membrane fraction from mutant Rhodobacter sphaeroides, which contains
      photosynthetic core complexes consisting of the reaction center and the light
      harvesting complex LH1. The selective recruitment to the patterned domains,
      governed primarily by electrostatic interactions, is confirmed by contact mode
      atomic force microscopy.

PMID- 16584211
TI  - Magnetic alteration of crystallite alignment converting powder to a pseudo single
      crystal.
AB  - The powder crystallites of L-alanine, selected for demonstration purposes,
      suspended in a photocurable resin were subjected to a frequency-modulated
      rotating magnetic field, and the achieved three-dimensional alignment was fixed
      by photopolymerization of the resin. The obtained sample exhibited the X-ray
      diffraction pattern that was comparable to the pattern of an equivalent actual
      original single crystal. This was achieved for the first time by the simultaneous
      alignment of the two magnetic axes, i.e., the easy and hard magnetization axes
      with respect to the space coordinates. A theoretical estimation indicates that a
      better alignment of the sample can be obtained if the sample preparation
      conditions are improved.

PMID- 16584210
TI  - Blood compatible carbon nanotubes--nano-based neoproteoglycans.
AB  - Although nanotechnology has provided a rich variety of nanomaterials (1-100 nm)
      for in vivo medical applications, the blood compatibility of all these
      nanobiomaterials is still largely unexamined. Here, we report the preparation of
      blood-compatible carbon nanotubes (CNTs) that potentially represent the building
      blocks for nanodevices having in vivo applications. Activated partial
      thromboplastin time (APTT) and thromboelastography (TEG) studies prove that
      heparinization can significantly enhance the blood compatibility of
      nanomaterials.

PMID- 16584213
TI  - Kinetics of desorption of alkanethiolates on gold.
AB  - Self-assembled monolayers (SAMs) of alkanethiols can undergo reductive desorption
      and oxidative re-adsorption. The Coulombic efficiency of the oxidative re
      adsorption reaction is dependent on the chain length and solution pH. We show
      that the loss of alkanethiols from the surface after reductive desorption can be
      explained by a simple model that takes into account diffusion of the thiolate
      into the bulk solution at a rate that is determined by the bulk solubility. These
      results provide a quantitative basis for the determination of the loss of
      alkanethiols from the surface after reductive desorption.

PMID- 16584212
TI  - Asymmetric distribution of phosphatidyl serine in supported phospholipid bilayers
      on titanium dioxide.
AB  - Supported phospholipid bilayers (SPBs) are useful for studying cell adhesion,
      cell-cell interactions, protein-lipid interactions, protein crystallization, and
      applications in biosensor and biomaterial areas. We have recently reported that
      SPBs could be formed on titanium dioxide, an important biomaterial, from vesicles
      containing anionic phospholipid phosphatidyl serine (PS) in the presence of
      calcium. Here, we show that the mobility of the fluorescently labeled PS present
      in these bilayers is severely restricted, whereas that of the zwitterionic
      phosphatidyl choline is not affected. Removal of calcium alleviated the
      restriction on the mobility of PS. Both components were found to be mobile in
      SPBs of identical compositions prepared in the presence of calcium on silica. To
      explain these results, we propose that, on TiO2, PS is trapped in the proximal
      leaflet of the bilayers. This proposal is supported by the results of protein
      adsorption experiments carried out on bilayers containing various amounts of PS
      prepared on silica and titania.

PMID- 16584214
TI  - Adsorption and spontaneous rupture of vesicles composed of two types of lipids.
AB  - To analyze the adsorption of single vesicles composed of two types of lipids
      (e.g., zwitterionic and positively charged lipids or zwitterionic and negatively
      charged lipids), we propose a statistical model taking into account lipid-surface
      interactions, lipid-lipid lateral interactions, and vesicle bending energy. Our
      treatment specifies how these parameters govern vesicle adsorption, shows how the
      radius of the vesicle-surface contact area may depend on the vesicle composition,
      and clarifies the conditions for vesicle rupture.

PMID- 16584215
TI  - From planar defect in opal to planar defect in inverse opal.
AB  - We demonstrate a facile method of fabricating opal and inverse opal structures
      with a planar defect. A single layer of silica beads was embedded into
      polystyrene opals by combining an inward-growing self-assembly method with spin
      coating technique. After the infiltration of silica followed by the removal of
      the polystyrene beads by calcination, an inverted structure was obtained. The
      silica beads were connected together by the infiltrated silica, thus a solid
      silica phase with the silica beads as a planar defect embedded in the inverse
      silica opal was obtained. The thickness of the defect layer can be adjusted by
      changing the size of the silica beads. Scanning electron microscope images showed
      the good quality of the crystal and the uniformity of the defect layer. Optical
      transmission spectra indicated the existence of a defect state induced by the
      defect layer in both the opal and inverse opal structures. High-cost techniques
      such as lithography and chemical vapor deposition are not involved in the
      fabrication of inverse opals with planar defects.

PMID- 16584216
TI  - One-pot synthesis of large FePt nanoparticles from metal salts and their thermal
      stability.
AB  - One-pot synthesis of FePt nanoparticles larger than 5 nm with controlled
      composition has been developed by the polyol reduction of platinum
      acetylacetonate and iron acetylacetonate in excess ligands. The obtained large
      FePt nanoparticles (6.1 +/- 0.6 nm Fe36Pt64, 5.8 +/- 0.7 nm Fe44Pt56, and 5.1 +/-
      0.7 nm Fe49Pt51 nanoparticles) were thermally more stable than the small ones and
      were hard to coalesce in the in-plane direction for their 2D superlattice.

PMID- 16584217
TI  - Cowpea mosaic virus for material fabrication: addressable carboxylate groups on a
      programmable nanoscaffold.
AB  - For the first time, decoration of surface-exposed carboxylate groups on Cowpea
      mosaic virus particles is reported, thus increasing the number and types of
      addressable surface groups on this nanoscaffold. First, the addressabilty of
      carboxylates was demonstrated using a carboxylate-selective fluorescent dye, N
      cyclohexyl-N'-(4-(dimethylamino)naphthyl)carbodiimide. Second, it was shown that
      the virions can be decorated with approximately 180 redox active,
      methyl(aminopropyl)viologen moieties by coupling to the surface carboxylates. The
      display of multiple redox centers on the virus particle surface may lead to the
      development of novel electron-transfer mediators in redox catalysis, to
      biosensors, and to nanoelectronic devices such as molecular batteries.

PMID- 16584218
TI  - Anisotropic fluctuation model for surfactant-laden liquid-liquid crystal
      interfaces.
AB  - A model for thermal fluctuations on surfactant-laden liquid-liquid crystal
      interfaces is formulated and used to derive the expression of the mean square
      displacement as a function of four elastic moduli of the interface. The
      measurable liquid crystal contributions to thermal roughness include the average
      molecular orientation, the interfacial anchoring modulus, and the bulk elasticity
      modulus. Surfactant-driven interfacial orientation transitions provide an
      additional means to extract interfacial elastic moduli parameters in surfactant
      laden liquid-liquid crystal interfaces in conjunction with thermal roughness
      measurements.

PMID- 16584219
TI  - Single-step DNA immobilization on antifouling self-assembled monolayers
      covalently bound to silicon (111).
AB  - Hydrosilylation of alkenes with epoxide-terminated tri(ethylene oxide) moieties
      on Si-H surfaces yields homogeneous monolayers for the efficient coupling of
      biomolecules. The wetting properties of the epoxide-functionalized surface allow
      for the spotting of solutions of biomolecules, making the surface amenable to
      microarraying. Immobilization of thiolated DNA was achieved in a single step to
      fabricate biorecognition interfaces showing the hybridization of complementary
      DNA at low concentrations and negligible binding of noncomplementary DNA.

PMID- 16584220
TI  - Formation of solid-supported lipid bilayers: an integrated view.
AB  - Supported lipid bilayers (SLBs) are popular models of cell membranes with
      potential bio-technological applications. A qualitative understanding of the
      process of SLB formation after exposure of small lipid vesicles to a hydrophilic
      support is now emerging. Recent studies have revealed a stunning variety of
      effects that can take place during this self-organization process. The ensemble
      of results in our group has revealed unprecedented insight into intermediates of
      the SLB-formation process and has helped to identify a number of parameters that
      are determinant for the lipid deposition on solid supports. The pathway of lipid
      deposition can be tuned by electrostatic interactions and by the presence of
      calcium. We emphasize the importance of the solid support in the SLB-formation
      process. Our results suggest that the molecular-level interaction between lipids
      and the solid support needs to be considered explicitly, to understand the
      rupture of vesicles and the formation of SLBs as well as to predict the
      properties of the resulting SLB. The impact of the SLB-formation process on the
      quality and the physical properties of the resulting SLB as well as implications
      for other types of surface-confined lipid bilayers are discussed.

PMID- 16584221
TI  - Control of colloidal particle deposit patterns within picoliter droplets ejected
      by ink-jet printing.
AB  - Particle deposit morphologies that resulted from evaporating ink-jetted
      microdroplets were controlled by varying the ink compositions and concentrations.
      The ink was a well-dispersed aqueous dispersion of monodisperse silica
      microspheres. Silica particles suspended in the microdroplet undergo self
      assembly upon the evaporation of the solvent. A ringlike deposit of the self
      assembled silica particles was produced from the water-based ink, while a uniform
      two-dimensional monolayer with a well-ordered hexagonal structure was obtained
      from the mixed-solvent-based inks. Variations in the deposit patterns can be
      explained in terms of competing effects between the convective and Marangoni
      flows, which vary with the types of the high-boiling-point solvent added to the
      ink. The macroscopic shape and microstructure of the silica colloidal deposits
      were observed by SEM, AFM, and a confocal microscope.

PMID- 16584222
TI  - Fluorometric and isothermal titration calorimetric studies on binding interaction
      of a telechelic polymer with sodium alkyl sulfates of varying chain length.
AB  - Steady-state fluorescence measurements and isothermal titration calorimetric
      experiments have been performed to study the interaction between a telechelic
      polymer, pyrene-end-capped poly(ethylene oxide) (PYPY), and sodium alkyl sulfate
      surfactants having decyl, dodecyl, and tetradecyl hydrocarbon tails. Fluorometric
      results suggest polymer-surfactant interaction in the very low range of polymer
      concentrations. The relative variation in the excimer to monomer pyrene emission
      intensities with varying surfactant concentration reveals that initial addition
      of surfactant favors intramolecular preassociation until the surfactant molecules
      start binding with the ethylene oxide (EO) chain. With the growing number of
      surfactant aggregates along the EO chain, the association becomes hindered due to
      the polyelectrolyte effect. The results from microcalorimetric titrations in the
      low concentration range of PYPY solution (approximately 10(-6) M) with alkyl
      sulfates suggest two kinds of surfactant-polymer interactions, one with the
      polymer hydrophobic end groups and the other with the ethylene oxide backbone.
      The overall polymer-surfactant interaction starts at a much lower surfactant
      concentration for the hydrophobically modified polymers compared to that in the
      case of unsubstituted poly(ethylene oxide) homopolymer. From the experiments
      critical aggregation concentration values and the second critical concentration
      where free micelles start forming have been determined. An endeavor has been made
      to unveil the mechanism underlying the corresponding associations of the
      surfactants with the polymer.

PMID- 16584223
TI  - Surface precipitation of highly porous hydrotalcite-like film on Al from a zinc
      aqueous solution.
AB  - A hydrotalcite-like film has been successfully deposited on an Al-bearing glass
      substrate based on an interface reaction between an Al layer and a zinc aqueous
      solution. The film selectively grew on the Al surface but not on the glass
      surface. The film on Al was composed of layered nanosheets of a hydrotalcite-like
      compound containing Al and Zn. Comparably, deposits on the plastic surface and
      precipitates in solution were wurzite-type ZnO with various morphologies
      depending upon the preparation conditions. At low supersaturation degrees, single
      crystals and superstructures of Zn-Al hydrotalcite were also obtained. This
      porous hydrotalcite film has a potential application as catalyst supports,
      environmental materials, or matrixes for hydrotalcite-based nanocomposite films.
      Using Al as a reaction interface makes it easy to coat porous hydrotalcites on a
      series of matrix materials varying in shapes and properties, which is important
      for achieving practical applications. In addition, the method developed should be
      widely applicable to other systems for the preparation of porous or oriented
      hydrotalcite-like thin films by an appropriate combination of divalent/trivalent
      solution-substrate systems.

PMID- 16584224
TI  - Interfacial composition and structural parameters of water/C12-s-C12 x 2Br/n
      hexanol/n-heptane microemulsions studied by the dilution method.
AB  - The interfacial composition of the stable water/C12-s-C12 x 2Br/n-hexanol/n
      heptane microemulsions has been studied in detail by dilution method. The results
      showed a marked maximum amount of the n-hexanol populating on the surfaces of
      droplets (represented as a = n(a)i/n(s), where n(a)i and n(s) are respectively
      the moles of n-hexanol and gemini surfactant on the surface of droplets) with
      increasing water content. At a constant level of water addition (the molar ratio
      of water to surfactant W0 = 20), a decreased with increasing the spacer length in
      the C12-s-C12 x 2Br molecule. The structural parameters of a w/o microemulsion
      were also estimated by analyzing the data of dilution experiments, and we found
      that the radius of the water pool was very sensitive to the increment of water
      content. The radius of the water pool varied from 0.74 to 5.35 nm with increasing
      W0 from 10 to 50. The variation extent reached 4.61 nm. In the cases of
      water/CPC/n-butanol/isopropyl myristate and water/CTAB/n-butanol/isopropyl
      myristate, however, the corresponding variation extents were only 1.22 and 1.68
      nm, respectively, when increasing comparable water content. The ratio of
      N(a)/N(2C), where N(a) and N(2C) are respectively the average numbers of n
      hexanol and the total average numbers of alkyl chains of gemini surfactant
      populating on per droplet surface, decreased obviously with increasing water
      content at W0 > 15. This indicated that C12-2-C12 x 2Br favored to form large
      droplets that were suitable to solubilize more water.

PMID- 16584226
TI  - Molecular-thermodynamic theory of micellization of pH-sensitive surfactants.
AB  - A predictive, molecular-thermodynamic theory is developed to model the
      micellization of pH-sensitive surfactants. The theory combines a molecular
      thermodynamic description of micellization in binary surfactant mixtures with the
      protonation equilibrium of the surfactant monomers. The thermodynamic component
      of the theory models the pH-mediated equilibrium between micelles, surfactant
      monomers, and counterions. These counterions may originate from the surfactant or
      from added salt, acid, or base. The molecular component of the theory models the
      various contributions to the free energy of micellization, which corresponds to
      the free-energy change associated with forming a mixed micelle from the
      protonated and deprotonated forms of the surfactant and from the bound
      counterions. The free energy of micellization includes hydrophobic, interfacial,
      packing, steric, electrostatic, and entropic contributions, which are all
      calculated molecularly. The theory also requires knowledge of the surfactant
      molecular structure and the solution conditions, including the temperature and
      the amount of any added salt, acid, or base. To account for the pH sensitivity of
      the surfactant, the theory requires knowledge of the surfactant monomer
      equilibrium deprotonation constant (pK1), which may be obtained from experimental
      titration data obtained below the critical micelle concentration (cmc). The
      theory can be utilized to predict the equilibrium micelle and solution
      properties, including the cmc, the micelle composition, the micelle shape and
      aggregation number, the solution pH, and the micelle deprotonation equilibrium
      constant (pKm). Theoretical predictions of the cmc, the micelle aggregation
      number, and the pKm compare favorably with the available experimental data for
      alkyldimethylamine oxide surfactants. This class of pH-sensitive surfactants
      exhibits a form of self-synergy, which has previously been attributed to hydrogen
      bond formation at the micelle interface. Instead, we show that much of the
      observed synergy is related to the electrostatic contribution to the free energy
      of micellization. Although we do not explicitly include hydrogen bonding in the
      molecular model of micellization, we briefly discuss how it may be incorporated
      and its anticipated effect on the predicted micellization behavior.

PMID- 16584225
TI  - Electrophoresis of diffuse soft particles.
AB  - A theory is presented for the electrophoresis of diffuse soft particles in a
      steady dc electric field. The particles investigated consist of an uncharged
      impenetrable core and a charged diffuse polyelectrolytic shell, which is to some
      extent permeable to ions and solvent molecules. The diffuse character of the
      shell is defined by a gradual distribution of the density of polymer segments in
      the interspatial region separating the core from the bulk electrolyte solution.
      The hydrodynamic impact of the polymer chains on the electrophoretic motion of
      the particle is accounted for by a distribution of Stokes resistance centers. The
      numerical treatment of the electrostatics includes the possibility of partial
      dissociation of the hydrodynamically immobile ionogenic groups distributed
      throughout the shell as well as specific interaction between those sites with
      ions from the background electrolyte other than charge-determining ions.
      Electrophoretic mobilities are computed on the basis of an original numerical
      scheme allowing rigorous evaluation of the governing transport and electrostatic
      equations derived following the strategy reported by Ohshima, albeit within the
      restricted context of a discontinuous chain distribution. Attention is
      particularly paid to the influence of the type of distribution adopted on the
      electrophoretic mobility of the particle as a function of its size, charge,
      degree of permeability, and solution composition. The results are systematically
      compared with those obtained with a discontinuous representation of the
      interface. The theory constitutes a basis for interpreting electrophoretic
      mobilities of heterogeneous systems such as environmental or biological colloids
      or swollen/deswollen microgel particles.

PMID- 16584227
TI  - Selection of surfactants for stable paraffin-in-water dispersions, undergoing
      solid-liquid transition of the dispersed particles.
AB  - A new experimental procedure is proposed for express evaluation of the
      coalescence stability of dispersions, in which the dispersed particles undergo
      solid-liquid phase transition. The procedure includes centrifugation of the
      dispersion concurrently with the phase transition of the particles and allows
      precise quantification of dispersion stability in terms of a critical pressure,
      at which the coalescence between the dispersed particles/drops takes place. The
      method is applied for studying the effects of surfactant type and concentration
      on the stability of paraffin-in-water dispersions, which have potential
      application in energy storage and transportation systems. Several types of water
      soluble surfactants (anionic, nonionic, and polymeric) are compared, whereas
      hexadecane or tetradecane is used as a dispersed phase. Most of the studied
      individual surfactants are found to be inefficient stabilizers (except for the
      nonionic Tween 40 and Tween 60). However, the dispersion stability increases
      significantly after the addition of appropriate cosurfactants, such as
      hexadecanol, Brij 52, or cocoamidopropyl betaine. Surfactants and cosurfactants
      with longer hydrophobic tails are better stabilizers than those with shorter
      tails. The obtained results are discussed from the viewpoint of the mechanisms of
      particle/drop coalescence during the solid-liquid-phase transition. The
      consistency and the undercooling temperatures of the studied dispersions are also
      discussed, because these properties are important for their practical
      applications. The proposed procedure for evaluation of dispersion stability and
      some of the conclusions could be relevant to food emulsions, in which dispersed
      fat particles undergo solid-liquid-phase transition of similar type.

PMID- 16584228
TI  - Assessment of the integrity of poly(caprolactone)-b-poly(ethylene oxide) micelles
      under biological conditions: a fluorogenic-based approach.
AB  - The integrity of block copolymer micelles is important for their effectiveness
      and successful delivery of the incorporated drugs. Here we evaluate the integrity
      of poly(caprolactone)-b-poly(ethylene oxide) micelles in media of varying
      chemical complexity and in cells by using fluorogenic micelles. Fluorogenic dye
      fluorescein-5-carbonyl azide diacetate was covalently attached to the micelle
      core-forming part of the block copolymer, poly(caprolactone). The fluorescence
      was not detectable unless the poly(caprolactone)21-b-poly(ethylene oxide)45
      micelles were destroyed and the fluorogenic dye was activated by
      deesterification. The fluorescence of the activated dye from destroyed micelles
      was easily detectable in various media and in cells. Micelles were stable in
      simple media such as phosphate-buffered saline but disassembled to varying
      extents with increasing chemical complexity of the media and addition of serum.
      The integrity of the internalized micelles within the cells showed a time
      dependent decrease but remained largely preserved (80%) after 20 h of incubation
      with cells. A proof of principle was also demonstrated in vivo in mice. The
      fluorogenic approach to micelle integrity assessment presented herein should lend
      itself to other block copolymer micelles and assessments of their integrity in
      complex biological systems in vitro and in vivo.

PMID- 16584230
TI  - Thermal control over the electrophoresis of soft colloidal particles.
AB  - We study the electrophoresis of surface-charged thermosensitive microgel
      particles based on poly-N-isopropylacrylamide (PNIPAM); these deswell with
      increasing temperature T. Our results show that the electrophoretic mobility mu
      is affected by the temperature-induced volume phase transition. It increases with
      increasing temperature, as a result of the charge density increase induced by
      particle deswelling. Temperature thus allows control of mu, in contrast to the
      more conventional charged hard spheres for which mu is T independent. Salt also
      affects the mu behavior and gives rise to rich phenomenology, sharing common
      characteristics with charged hard spheres and polyelectrolyte-coated colloids
      depending on whether the microgels are swollen or deswollen. We interpret the
      effects of salt concentration n by considering that particle charges are located
      in an external shell, as confirmed by titrations, and that it is this shell-salt
      induced compression that affects the resulting mu behavior.

PMID- 16584229
TI  - Cationic liposomes in mixed didodecyldimethylammonium bromide and
      dioctadecyldimethylammonium bromide aqueous dispersions studied by differential
      scanning calorimetry, Nile Red fluorescence, and turbidity.
AB  - The thermotropic phase behavior of cationic liposomes in mixtures of two of the
      most investigated liposome-forming double-chain lipids,
      dioctadecyldimethylammonium bromide (DODAB) and didodecyldimethylammonium bromide
      (DDAB), was investigated by differential scanning calorimetry (DSC), turbidity,
      and Nile Red fluorescence. The dispersions were investigated at 1.0 mM total
      surfactant concentration and varying DODAB and DDAB concentrations. The gel to
      liquid-crystalline phase transition temperatures (Tm) of neat DDAB and DODAB in
      aqueous dispersions are around 16 and 43 degrees C, respectively, and we aim to
      investigate the Tm behavior for mixtures of these cationic lipids. Overall, DDAB
      reduces the Tm of DODAB, the transition temperature depending on the DDAB
      content, but the Tm of DDAB is roughly independent of the DODAB concentration.
      Both DSC and fluorescence measurements show that, within the mixture, at room
      temperature (ca. 22 degrees C), the DDAB-rich liposomes are in the liquid
      crystalline state, whereas the DODAB-rich liposomes are in the gel state. DSC
      results point to a higher affinity of DDAB for DODAB liposomes than the reverse,
      resulting in two populations of mixed DDAB/DODAB liposomes with distinctive phase
      behavior. Fluorescence measurements also show that the presence of a small amount
      of DODAB in DDAB-rich liposomes causes a pronounced effect in Nile Red emission,
      due to the increase in liposome size, as inferred from turbidity results.

PMID- 16584231
TI  - Asp-Gly based peptides confined at the surface of cationic gemini surfactant
      aggregates.
AB  - Cationic gemini surfactants complexed with anionic oligoglycine-aspartate (called
      gemini peptides hereafter) were synthesized, and their aggregation behaviors were
      studied. The effects of the hydrophobic chain length (C10-C22) and the length of
      the oligoglycine (0-4) were investigated, and it was clearly shown by critical
      micellar concentration, Krafft temperature, and isothermal surface pressure
      measurements that the hydrophobic effect and interpeptidic interaction influence
      the aggregation behavior in a cooperative manner. Below their Krafft
      temperatures, some of them formed both hydro- and organogels with three
      dimensional networks and the Fourier transform infrared measurements show the
      presence of interpeptidic hydrogen bonds.

PMID- 16584232
TI  - Experimental study of structure and dynamics in a monolayer of paramagnetic
      colloids confined by parallel hard walls.
AB  - We study the structural and dynamical properties of paramagnetic colloidal
      spheres interacting as repulsive dipoles in two dimensions and confined between
      parallel hard walls. We observed that the structure and dynamics of the self
      assembled colloids are strongly dependent upon the width of the confining
      channel. The system exhibits re-entrant behavior as a function of the channel
      width, transitioning from solid-like to liquid-like repeatedly in excellent
      agreement with simulation results. For large channels, an ordered layered
      structure self-assembles near the walls, but this local structure is not
      commensurate with the bulk structure, leading to localized stable defects.

PMID- 16584233
TI  - Phenol photodegradation on platinized-TiO2 photocatalysts related to charge
      carrier dynamics.
AB  - Three commercial TiO2 compounds (Degussa P25, Sachtleben UV100, and Millenium
      PC50) and their platinized forms have been studied by the time-resolved microwave
      conductivity (TRMC) method to follow their charge-carrier dynamics and to relate
      it to the photocatalytic activity for phenol degradation in TiO2 aqueous
      suspensions. The degradation reaction has been studied in detail, following the
      time evolution of the concentration of phenol and its intermediates by liquid
      chromatography. The results show that platinization has a distinct influence on
      the commercial compounds, decreasing globally the activity of P25 and increasing
      the activity of PC50 and UV100. An influence of charge-carrier lifetimes on the
      photoactivity of pure and platinized TiO2 samples has been evidenced.

PMID- 16584234
TI  - Predicting solute adsorption on activated carbon: phenol.
AB  - Activated carbon (AC), the most widely used adsorbent in water and in wastewater
      treatment, comprises a high surface area of very small, convoluted and
      interconnected pores. Despite the wide use of AC, there is little fundamental
      atomic-level understanding of its adsorption capacity and selectivity as well as
      its pore structure. The purpose of this work is to suggest the methodology for
      calculation of equilibrium adsorption capacity of common water organic pollutants
      and use it for phenol as a model. The effects of various functional groups, pore
      size, and coverage on thermodynamics of phenol adsorption from the gas phase and
      from water media are calculated using molecular mechanics (MM) and density
      functional theory (DFT) approaches.

PMID- 16584235
TI  - Superficial wrinkles in stretched, drying gelatin films.
AB  - When a thin film of initially hydrated gelatin is allowed to dry from the
      surface, superficial changes in the structure of the material affect the local
      mechanical properties of the drying region. If the film is simultaneously
      subjected to large strain deformation (above 20%), a periodic pattern of wrinkles
      appears on the surface of the gelatin along the length of the sample in the
      direction of the applied force. These wrinkles are uniformly distributed on the
      surface of the gelatin with a wavelength that is much smaller than the sample
      thickness, which changes with sample composition, aging time, and deformation
      rate. We investigate these patterns via in situ environmental scanning electron
      microscopy (ESEM) and provide a theory for their origin.

PMID- 16584236
TI  - Formation of alkanethiol and alkanedithiol monolayers on GaAs(001).
AB  - The formation of alkanethiol (H-(CH2)n-SH, n = 8-18) and 1,8-octanedithiol (HS
      (CH2)8-SH) monolayer films on n-type GaAs(001) has been systematically studied.
      We observed a nonlinear dependence of the film thickness on molecular length,
      which is drastically different from monolayer films of the same molecules on
      metals. For 8 < or = n < or = 14, the films are only 3-4.5 A thick, significantly
      smaller than the corresponding molecular length. For n = 16 and 18, the measured
      film thicknesses were 9 and 11 A, respectively, consistent with molecules
      orienting with a tilt angle of approximately 60 degrees from the surface normal.
      Unlike the alkanethiols, the thickness of the 1,8-octanedithiol monolayer is
      almost the same as its molecular length, indicating that dithiol molecules orient
      vertically with only one thiol end group bound to the GaAs surface. Additional
      support for this conclusion comes from the fact that X-ray photoelectron
      spectroscopy of the 1,8-octanedithiol monolayer clearly resolves two types of S
      atoms in the monolayer: those bound to the GaAs surface and those existing as
      free thiols. A suggestion was made on the mechanisms for alkanethiol and
      alkanedithiol monolayer formation.

PMID- 16584238
TI  - Adsorbed structures of 4,4'-bipyridine on Cu(111) in acid studied by STM and IR.
AB  - The adsorption of 4,4'-bipyridine (BiPy) on Cu(111) has been investigated in 0.1
      M HClO4 by cyclic voltammetry, electrochemical scanning tunneling microscopy
      (STM), and surface-enhanced infrared adsorption spectroscopy (SEIRAS). Cyclic
      voltammetry showed the double layer region extending from -0.2 to 0.26 V and a
      pair of redox waves superposing on hydrogen evolution wave at more negative
      potentials. Diprotonated BiPy, BiPyH2(2+), is adsorbed flat on the Cu(111) (1 x
      1) surface and forms a well-ordered monolayer with a (3 x 4) symmetry in the
      double-layer potential region. At more negative potential, BiPyH2(2+) is reduced
      to its monocation radical, BiPyH2(*+), and forms another well-ordered structure
      in which the radicals are stacked in molecular rows with a face-to-face self
      dimer as the building unit. The SEIRA spectra of both BiPyH2(2+) and BiPyH2(*+)
      are dominated by gerade modes which should be IR-inactive for the centrosymmetric
      species. The breakdown of the selection rule of IR absorption is ascribed to the
      vibronic coupling associated with charge transfer between BiPyH2(2+) and the
      surface and between the radicals.

PMID- 16584237
TI  - Surface-deposited acid/base on glass microfibers in formation of (3
      aminopropyl)triethoxysilane-[2-(3,4
      epoxycyclohexyl)ethyl]heptaisobutyloctasilsesquioxane bioverlay.
AB  - Silanization of macroporous glass microfiber filters with (3
      aminopropyl)triethoxysilane (APTES) and subsequent binding of [2-(3,4
      epoxycyclohexyl)ethyl]heptaisobutyloctasilsesquioxane (E-POSS) to the amine
      terminated surface of microfibers was studied. Prior to the silanization, minute
      quantities of concentrated aqueous solutions of hydrochloric acid or ammonia were
      adsorbed in the filters while attachment of E-POSS molecules to APTES overlay was
      not specially catalyzed. Analysis of DRIFT, XPS, and 13C CP/MAS NMR spectra has
      shown that the formation of APTES overlay is affected differently by the surface
      deposited acid or base. It was proved by XPS that microfibers with the adsorbed
      acid take up higher amounts of covalently attached APTES by 42% and,
      subsequently, of E-POSS by 65% than microfibers with the adsorbed ammonia. The
      molecular mechanics model calculations, which were made using silica as a
      template, have shown that approximately two-layered APTES coating can be built on
      the model surface if complete hydrolysis of ethoxy groups and vertical
      condensation of APTES species are assumed.

PMID- 16584239
TI  - Combined STM and FTIR characterization of terphenylalkanethiol monolayers on
      Au(111): effect of alkyl chain length and deposition temperature.
AB  - Self-assembled monolayers (SAMs) of 4,4'-terphenyl-substituted alkanethiols
      C6H5(C6H4)2(CH2)n-SH (TPn, n = 1-6) on Au (111) substrates were studied using
      scanning tunneling microscopy (STM) and infrared reflection absorption
      spectroscopy (IRRAS). When the SAMs were prepared at room temperature (RT, 298
      K), TPn films (except TP2) exhibit an odd-even effect regarding both molecular
      orientation and packing density. For all investigated films, STM data reveals the
      presence of a large degree of lateral order. In the case of odd-numbered TPns,
      the films revealed a (2 square root(3) x square root(3))R30 degree molecular
      arrangement. For the even-numbered TP4 and TP6 SAMs, a c(5 square root(3) x 3)
      rectangular unit cell was found. The packing density for the even-numbered TPn
      SAMs is 25% lower than that for the odd-numbered TPn SAMs. When the SAMs were
      prepared at 333 K, the even-numbered SAMs were found to form structures with a
      significantly lower packing density. In the case of TP2, instead of the (2 square
      root(3) x square root(3))R30 degree structure formed at room temperature, a c(5
      square root(3) x 3) structure was observed. For TP6 SAMs, the room-temperature
      c(5 square root(3) x 3) structure was replaced by a (6 square root(3) x 2 square
      root(3))R30 degree structure.

PMID- 16584240
TI  - Fabrication of metal nanoparticle monolayers on amphiphilic poly(amido amine)
      dendrimer Langmuir films.
AB  - A newly designed 1.5th generation poly(amido amine) dendrimer with an azacrown
      core, hexylene spacers, and octyl terminals was spread on gold nanoparticle (Au
      NP) suspension. The surface pressure-area isothermal curves indicated that the
      molecular area of dendrimer on Au-NP suspension was significantly smaller than
      that on water, indicating the formation of dendrimer/Au-NP composites. The
      dendrimer Langmuir films on the Au-NP suspension were transferred to copper grids
      at various surface pressures and observed by transmission electron microscopy.
      The transferred films consisted of a fractal-like network of nanoparticles at low
      surface pressure and of a defect-rich monolayer of nanoparticles at high surface
      pressure. From these results, it was suggested that the dendrimers bind Au-NPs,
      and dendrimer/Au-NP composites formed networks or monolayers at the interface.
      From the intensity decrease of the Au plasmon band of Au-NP suspension after the
      formation of composite, it was estimated that some (approximately 14) dendrimer
      molecules bind to one Au-NP. Furthermore, neutron reflectivity at the
      air/suspension interface and X-ray reflectivity of the film transferred on a
      silicon substrate revealed that the dendrimer molecules are localized on the
      upper-half surface of Au-NP. Metal affinity of azacrown, flexibility of hexylene
      spacer, and amphiphilicity of dendrimer with octyl terminals played important
      roles for the formation of dendrimer/Au-NP hybrid films. The present
      investigation proposed a new method to fabricate the self-assembled functional
      polymer/nanoparticle hybrid film.

PMID- 16584241
TI  - Characterization of watermarks formed in nano-carpet effect.
AB  - In the spreading of a water droplet on an aligned silicon nanorod array surface,
      a precursor rim was detected moving ahead of the contact line. In this process,
      nanorods were bundled by the capillary force to form clusters, and a watermark
      developed on the surface after water evaporated. The size of the watermark,
      R(p)max, corresponding to the maximum radius of the precursor rim, followed a
      simple power law relationship with the volume of water droplet omega, R(p)max
      proportional to omega(beta). The scaling exponent beta increased when the nanorod
      height decreased, but all in the vicinity of 1/3. This behavior was attributed to
      the competition of evaporation and spreading of a water droplet during the
      spreading process. The size of the bundled nanorod cluster formed by the
      capillary force not only depended on the nanorod height but also on the location
      in the watermark. The cluster size almost remained as a constant near the center,
      and then it decreased with the distance from the center. This phenomenon can be
      qualitatively interpreted through the change of the total free energy during the
      precursor invading the nanorod array, by considering the contribution from the
      mechanical energy change due to the bending and clustering of nanorods.

PMID- 16584242
TI  - Thermodynamics of the liquid expanded to condensed phase transition of poly(L
      lactic acid) in Langmuir monolayers.
AB  - Surface pressure-area per monomer (pi-A) isotherms show that poly(L-lactic acid)
      (PLLA) Langmuir monolayers exhibit a liquid expanded-to-condensed (LE/LC) phase
      transition at low surface pressure. Brewster angle microscopy images show
      circular domains where the LC phase is surrounded by the LE phase during phase
      coexistence. Morphology studies via atomic force microscopy show that well
      ordered patterns are only observed for Langmuir-Blodgett films prepared in the LC
      phase, while no ordered features are observed in the LE phase. The morphological
      differences confirm that during the LE/LC phase transition PLLA molecules form
      well-ordered structures at the air/water interface. Analysis by the two
      dimensional Clausius-Clapeyron equation is used to predict the critical
      parameters (X(c)). Both critical parameters, the critical temperature (T(c)) and
      the critical pressure (pi(c)), increase with increasing number average molar mass
      (M(n)) as X(c) = X(c,infinity) - KM(n)(-1), where X(c,infinity) is the value of
      the critical parameter at infinite molar mass and K is a constant. For PLLA
      T(c,infinity) = 36.2 +/- 0.3 degrees C and pi(c,infinity) = 4.53 +/- 0.06 mN x m(
      1). This study provides a model polymer system for examining critical behavior in
      two dimensions.

PMID- 16584243
TI  - Bending elasticity of charged surfactant layers: the effect of layer thickness.
AB  - The bending properties of charged one-component surfactant films of finite
      thickness have been theoretically investigated. It is demonstrated that finite
      thickness effects are of crucial importance for layers formed by an ionic
      surfactant with a flexible hydrophobic tail, whereas the influence on layers
      formed by a surfactant with a rigid tail is less pronounced. As a matter of fact,
      in the former case, the spontaneous curvature and mean and Gaussian bending
      constants all become significantly modified as compared to an infinitely thin
      surface and assume identical values as if the surfactant layer were bent at
      constant layer thickness. As a result, the spontaneous curvature is found to
      decrease, whereas the magnitudes of the mean and Gaussian bending constants both
      increase with increasing layer thickness as well as with increasing hydrophobic
      hydrophilic interfacial tension. All of these trends are consistent with
      experimental observations. In addition, it is demonstrated that separating the
      hydrophilic-hydrophobic interface and the surface of charge a certain distance
      from each other tends to increase the spontaneous curvature and the mean bending
      constant, whereas the Gaussian bending constant becomes increasingly negative. It
      is also found that the work of bending a bilayer into a geometrically closed
      vesicle is substantially raised to large positive values for surfactants with
      flexible aliphatic chains, whereas the corresponding quantity is negative for
      surfactants with rigid tails, indicating that stable bilayer structures may only
      be formed by the former surfactant. Furthermore, each of the bending elasticity
      constants for monolayers formed by a double-chain ionic surfactant are found to
      assume lower values as compared with layers formed by the corresponding single
      chain surfactant.

PMID- 16584244
TI  - Evolution of interparticle capillary forces during drying of colloidal crystals.
AB  - Photonic crystals are periodic structures that have the capability to manipulate
      the photons in the same way as semiconductors do for electrons. The self-assembly
      strategy that utilizes colloidal crystals as a template to form photonic crystals
      has received a great deal of recent research interest because it is simple and
      cost-effective. Experimental studies and theoretical analysis have speculated
      that capillary forces play a pivotal role in forming the colloidal crystals
      during the crystal growth process and that particularly during the drying stage
      the changing of the magnitude of capillary forces is critical to the resultant
      microstructure. This paper presents a computational analysis of the changing
      capillary forces, which may throw light on a refined strategy for controlling
      colloidal crystal growth.

PMID- 16584246
TI  - Testing predictions of macroscopic binary diffusion coefficients using lattice
      models with site heterogeneity.
AB  - Quantitatively predicting mass transport rates for chemical mixtures in porous
      materials is important in applications of materials such as adsorbents,
      membranes, and catalysts. Because directly assessing mixture transport
      experimentally is challenging, theoretical models that can predict mixture
      diffusion coefficients using only single-component information would have many
      uses. One such model was proposed by Skoulidas, Sholl, and Krishna (Langmuir,
      2003, 19, 7977), and applications of this model to a variety of chemical mixtures
      in nanoporous materials have yielded promising results. In this paper, the
      accuracy of this model for predicting mixture diffusion coefficients in materials
      that exhibit a heterogeneous distribution of local binding energies is examined.
      To examine this issue, single-component and binary mixture diffusion coefficients
      are computed using kinetic Monte Carlo for a two-dimensional lattice model over a
      wide range of lattice occupancies and compositions. The approach suggested by
      Skoulidas, Sholl, and Krishna is found to be accurate in situations where the
      spatial distribution of binding site energies is relatively homogeneous, but is
      considerably less accurate for strongly heterogeneous energy distributions.

PMID- 16584245
TI  - ATR-IR spectroscopy of pendant NH2 groups on silica involved in the Knoevenagel
      condensation.
AB  - The liquid-phase Knoevenagel condensation between benzaldehyde and ethyl
      cyanoacetate catalyzed by aminopropyl-modified silica has been investigated using
      in situ attenuated total reflection infrared (ATR-IR) spectroscopy. The aim of
      the work was to demonstrate the different levels of information on the reaction
      mechanism that can be achieved by operating the spectroscopic cell in the absence
      and in the presence of a solvent, in flow-through and stop-flow modes and in
      combination with concentration modulation spectroscopy. The reaction mechanism
      involves the formation of an imine intermediate whose existence has been verified
      in situ by combining in one experiment continuous and stop-flow operations.
      Identical information has been gained more elegantly using concentration
      modulation spectroscopy, which additionally provided information on the possible
      origin of the solvent effect observed in the Knoevenagel reaction. Faster
      production and consumption of the imine intermediate was observed in cyclohexane
      solvent than in toluene. Identification of other species evolving on the catalyst
      surface and monitoring of the effluents of the spectroscopic cell provided some
      insight in possible catalyst deactivation.

PMID- 16584247
TI  - Investigation into pH-responsive self-assembled monolayers of acylated
      anthranilate-terminated alkanethiol on a gold surface.
AB  - This article describes the preparation of pH-responsive self-assembled monolayers
      (SAMs) of acylated anthranilate-terminated alkanethiol. These monolayers are
      formed by chemisorption of the alkanethiol molecules onto a gold surface,
      resulting in different wetting properties of the surfaces depending upon the pH.
      By using various characterization techniques (e.g., infrared spectroscopy, cyclic
      voltammetry, contact angle measurements, and surface energy analysis), we have
      found that the changes in the wetting properties originate from the different
      surface structures of the monolayers in different pH environments. From surface
      energy analysis, we found that the disperse components of the surface energy on
      such SAMs predominate after treatment with pH 1 water, whereas the polar
      components of the surface energy on such SAMs predominate after treatment with pH
      13 water. It is greatly anticipated that this line of research will provide new
      insight into the mechanism behind pH-responsive properties, facilitating the
      design and synthesis of new surface-active molecules for the fabrication of pH
      responsive functional surfaces.

PMID- 16584248
TI  - Ethanol, acetic acid, and water adsorption from binary and ternary liquid
      mixtures on high-silica zeolites.
AB  - Adsorption isotherms were measured for ethanol, acetic acid, and water adsorbed
      on high-silica ZSM-5 zeolite powder from binary and ternary liquid mixtures at
      room temperature. Ethanol and water adsorption on two high-silica ZSM-5 zeolites
      with different aluminum contents and a high-silica beta zeolite were also
      compared. The amounts adsorbed were measured using a recently developed technique
      that accurately measures the changes in adsorbent/liquid mixture density and
      liquid concentration. This technique allows the adsorption of each compound in a
      liquid mixture to be measured. Adsorption data for binary mixtures were fit with
      the dual-site extended Langmuir model, and the parameters were used to predict
      ternary adsorption isotherms for each compound with reasonable accuracy. In
      ternary mixtures, acetic acid competed with ethanol and water for adsorption
      sites and reduced ethanol adsorption more than it reduced water adsorption.

PMID- 16584249
TI  - DNA micropatterning on polycrystalline diamond via one-step direct amination.
AB  - We report a novel method of one-step direct amination on polycrystalline diamond
      to produce functionalized surfaces for DNA micropatterning by photolithography.
      Polycrystalline diamond was exposed to UV irradiation in ammonia gas to generate
      amine groups directly. After patterning, optical microscopy confirmed that
      micropatterns covered with an Au mask were regular in size and shape. The regions
      outside the micropatterns were passivated with fluorine termination by C3F8
      plasma, and the chemical changes on the two different surfaces--the amine groups
      inside the patterned regions by one-step direct amination and fluorine
      termination outside the patterned regions--were characterized by spatially
      resolved X-ray photoelectron spectroscopy (XPS). The patterned areas terminated
      with active amine groups were then immobilized with probe DNA via a bifunctional
      molecule. The sequence specificity was conducted by hybridizing fluorescently
      labeled target DNA to both complementary and noncomplementary probe DNA attached
      inside the micropatterns. The fluorescence micropatterns observed by
      epifluorescence microscopy corresponded to those imaged by optical microscopy.
      DNA hybridization and denaturation experiments on a DNA-modified diamond show
      that the diamond surfaces reveal superior stability. The influence of a different
      amination time on fluorescence intensity was compared. Different terminations as
      passivated layers were investigated, and as a result, fluorine termination points
      to the greatest signal-to-noise ratio.

PMID- 16584250
TI  - Molecular mechanism and thermodynamics study of plasmid DNA and cationic
      surfactants interactions.
AB  - The molecular mechanism and thermodynamics of the interactions between plasmid
      DNA and cationic surfactants were investigated by isothermal titration
      calorimetry (ITC), dynamic light scattering, surface tension measurements, and UV
      spectroscopy. The cationic surfactants studied include
      benzyldimethyldodecylammonium chloride, benzyldimethyltetradecylammonium
      chloride, cetylpyridinium chloride, and cetyltrimethylammonium chloride. The
      results indicate a critical aggregation concentration (cac) of a surfactant:
      above the cac the surfactant forms aggregates with plasmid DNA; below the cac,
      however, there is no detectable interaction between DNA and surfactant.
      Surfactants with longer hydrocarbon chains have smaller cac, indicating that
      hydrophobic interaction plays a key role in DNA-surfactant complexation.
      Moreover, an increase in ionic strength (I) increases the cac but decreases the
      critical micellization concentration (cmc). These opposite effects lead to a
      critical ionic strength (I(c)) at which cac = cmc; when I < I(c), cac < cmc; when
      I > I(c), DNA does not form complexes with surfactant micelles. In the
      interaction DNA exhibits a pseudophase property as the cac is a constant over a
      wide range of DNA concentrations. ITC data showed that the reaction is solely
      driven by entropy because both deltaH(o) (approximately 2-6 kJ mol(-1)) and
      deltaS(o) (approximately 70-110 J K(-1) mol(-1)) have positive values. In the
      complex, the molar ratio of DNA phosphate to surfactant is in the range of 0.63
      1.05. The reaction forms sub-micrometer-sized primary particles; those aggregate
      at high surfactant concentrations. Taken together, the results led to an
      inference that there is no interaction between surfactant monomers and DNA
      molecules and demonstrated that DNA-cationic surfactant interactions are mediated
      by the hydrophobic interactions of surfactant molecules and counterion binding of
      DNA phosphates to the cationic surfactant aggregates.

PMID- 16584251
TI  - Aggregation behavior and thermodynamics of binding between poly(ethylene oxide)
      block-poly(2-(diethylamino)ethyl methacrylate) and plasmid DNA.
AB  - The aggregation behavior and the thermodynamics of binding between poly(ethylene
      oxide)-block-poly(2-(diethylamino)ethyl methacrylate) (PEO-b-PDEAEMA) block
      copolymers and plasmid DNA were examined. Binding between the polymer and DNA
      were confirmed by gel electrophoresis. The high affinity between the polymer and
      DNA was demonstrated through the ethidium bromide (EtBr) displacement assay, and
      the binding was found to be related to the stoichiometric balance between the
      amine group of the polymer and the DNA nucleotide molar ratio (N/P molar ratio).
      The light scattering and TEM results showed that, at low polymer concentration,
      the hydrodynamic radii (R(h)) of the polymer/DNA complexes was around 90 nm;
      however, at sufficiently high polymer concentration, the complexes condensed to
      around 35 nm induced by a structural rearrangement of the amphiphilic nature of
      the block copolymer. The isothermal titration calorimetric results showed that
      the binding between the polymer and DNA is driven by a large favorable enthalpy.

PMID- 16584252
TI  - Protein-resistant polymer coatings on silicon oxide by surface-initiated atom
      transfer radical polymerization.
AB  - The modification of silicon oxide with poly(ethylene glycol) to effectively
      eliminate protein adsorption has proven to be technically challenging. In this
      paper, we demonstrate that surface-initiated atom transfer radical polymerization
      (SI-ATRP) of oligo(ethylene glycol) methyl methacrylate (OEGMA) successfully
      produces polymer coatings on silicon oxide that have excellent protein resistance
      in a biological milieu. The level of serum adsorption on these coatings is below
      the detection limit of ellipsometry. We also demonstrate a new soft lithography
      method via which SI-ATRP is integrated with microcontact printing to create
      micropatterns of poly(OEGMA) on glass that can spatially direct the adsorption of
      proteins on the bare regions of the substrate. This ensemble of methods will be
      useful in screening biological interactions where nonspecific binding must be
      suppressed to discern low probability binding events from a complex mixture and
      to pattern anchorage-dependent cells on glass and silicon oxide.

PMID- 16584253
TI  - Adhesion forces between hybrid colloidal particles and concanavalin A.
AB  - Hybrid particles of poly(methyl methacrylate) and carboxymethylcellulose,
      PMMA/CMC, were attached to atomic force microscopy cantilevers and probed against
      concanavalin A (ConA) films formed either on Si wafers or on CMC substrate.
      Regardless of the substrate, the approach curves showed different inclinations,
      indicating that the probe first touches a soft surface and then a hard substrate.
      The distance corresponding to the soft layer was estimated as 20 +/- 10 nm and
      was attributed to the CMC layers attached to the hybrid particles surfaces.
      Probing PMMA/CMC particles against ConA adsorbed onto Si wafers yielded retract
      curves with a sawlike pattern. The average range of adhesion forces (maximum pull
      off distance) and mean adhesion force were estimated as 100 +/- 40 nm and -11 +/-
      7 nN, respectively, evidencing multiple adhesions between CMC sugar residues and
      ConA. However, upon probing against ConA adsorbed onto CMC substrates, the mean
      pull-off distance and mean adhesion force were reduced to 37 +/- 18 nm and -3 +/-
      1 nN, respectively, indicating that the ConA molecules immobilized onto CMC films
      are less available to interact with the hybrid particle than the ConA molecules
      adsorbed onto Si wafers. Another set of experiments, where PMMA/CMC particle
      probed against ConA-covered Si wafers in the presence of mannose, showed that the
      addition of mannose led to a considerable decrease in the mean adhesion force
      from -11 +/- 7 to -3 +/- 1 nN. Two hypotheses have been considered to explain the
      effect caused by mannose addition. The first suggested the desorption of ConA
      from the substrate so that the hybrid particle would probe bare Si wafer (weak
      adhesion). The second proposed the adsorption of mannose onto the ConA layer so
      that mannose layer would probe against another mannose layer, leading to low
      adhesion forces. In situ ellipsometry and capillary electrophoresis have been
      applied to check the hypotheses.

PMID- 16584254
TI  - Bionanofabrication of metallic and semiconductor nanoparticle arrays using S
      layer protein lattices with different lateral spacings and geometries.
AB  - Two-dimensional (2-D) surface layer (S-layer) protein lattices isolated from the
      gram-positive bacterium Deinococcus radiodurans and the acidothermophilic
      archaeon Sulfolobus acidocaldarius were investigated and compared for their
      ability to biotemplate the formation of self-assembled, ordered arrays of
      inorganic nanoparticles (NPs). The NPs employed for these studies included
      citrate-capped gold NPs and various species of CdSe/ZnS core/shell quantum dots
      (QDs). The QD nanocrystals were functionalized with different types of thiol
      ligands (negative- or positive-charged/short- or long-chain length) in order to
      render them hydrophilic and thus water-soluble. Transmission electron microscopy,
      Fourier transform analyses, and pair correlation function calculations revealed
      that ordered nanostructured arrays with a range of spacings (approximately 7-22
      nm) and different geometrical arrangements could be fabricated through the use of
      the two types of S-layers. These results demonstrate that it is possible to
      exploit the physicochemical/structural diversity of prokaryotic S-layer scaffolds
      to vary the morphological patterning of nanoscale metallic and semiconductor NP
      arrays.

PMID- 16584255
TI  - Perturbation of phospholipid bilayer properties by ethanol at a high
      concentration.
AB  - Atomistic molecular dynamics (MD) simulations have been carried out at 30 degrees
      C on a fully hydrated liquid crystalline lamellar phase of
      dimyrystoylphosphatidylcholine (DMPC) lipid bilayer with embedded ethanol
      molecules at 1:1 composition, as well as on the pure bilayer phase. The ethanol
      molecules are found to exhibit a preference to occupy regions near the upper part
      of the lipid acyl chains and the phosphocholine headgroups. The calculations
      revealed that the phosphocholine headgroup dipoles (P- --> N+) of the lipids
      prefer to orient more toward the aqueous layer in the presence of ethanol. It is
      noticed that the ethanol molecules modify the dynamic properties of both lipids
      as well as the water molecules in the hydration layer of the lipid headgroups.
      Both the in-plane "rattling" and out-of-plane "protrusion" motions of the lipids
      have been found to increase in the presence of ethanol. Most importantly, it is
      observed that the water molecules within the hydration layer of the lipid
      headgroups exhibit faster translational and rotational motions in the presence of
      ethanol. This arises due to faster dynamics of hydrogen bonds between lipid
      headgroups and water in the presence of ethanol.

PMID- 16584256
TI  - In-situ encapsulation of quantum dots into polymer microspheres.
AB  - We have incorporated fluorescent quantum dots (QDs) into polystyrene microspheres
      using functionalized oligomeric phosphine (OP) ligands. We find that a uniform
      distribution of quantum dots is loaded inside each polymer bead. Some local close
      packing of quantum dots in the beads is attributed to the self-polymerization of
      the functionalized ligands. The presence of quantum dots disturbs the nucleation
      and growth processes during the formation of polymer microspheres and results in
      a wider size distribution of the quantum dot-embedded polystyrene beads than for
      the control without dots. The change in quantum efficiency of the quantum dots
      before (approximately 20%) and after (12%) loading into the beads substantiates
      the protection of oligomeric phosphine ligands yet indicates that the properties
      of these quantum dots are still affected during processing.

PMID- 16584257
TI  - Development of mesophase pitch derived mesoporous carbons through a commercially
      nanosized template.
AB  - Mesoporous carbons (MCs) with a high surface area (up to 900 m2/g), large pore
      volume (up to 2.1 cm3/g), high mesopore ratio (94%), and high yield (70%) were
      successfully prepared from an AR mesophase pitch, using a commercially nanosized
      silica template. The removal of the template provided some larger mesopores of 25
      50 nm (pore I) with a surface area of ca. 300 m2/g, while the successive
      carbonization opened the closed pores within the carbon body to give smaller
      mesopores of 2-10 nm (pore II) with a similar surface area. During the
      carbonization of pitch precursor, the evaporation of volatile components swells
      the carbon to introduce the second mesopores among the domains and even
      microdomain units because of their rearrangements and overlappings in the
      process. The addition of iron salt with the silica template resulted in a
      remarkable increase of the surface area (ca. 300 m2/g) by introducing mesopores
      of 3-5 nm. The resultant MCs maintained some graphitizable natures derived from
      the anisotropic precursor. Their graphitization at 2400 degrees C provided the
      graphitic structure with large surface areas (270-460 m2/g) and mesoporosity.

PMID- 16584258
TI  - Temperature effects on the composition and microstructure of spray-dried
      nanocomposite powders.
AB  - Porous composite powders, prepared by spray drying of silica and polybromostyrene
      nanoparticles, were calcined at various temperatures up to 750 degrees C. The
      structure in these powders are quantitatively investigated by ultra small-angle X
      ray scattering, thermogravimetric analysis, and nuclear magnetic resonance
      measurements. It has been found that the polybromostyrene latex is efficient in
      templating mesopores. However, polybromostyrene remains almost completely in the
      interstitial micropores in the grain after the spray-drying process. A post
      thermal treatment of the powders has been applied from 250 up to 750 degrees C.
      We found that the hydrocarbon part of the polybromostyrene is decomposed and
      leaves the micropores at around 350 degrees C. However, it is demonstrated that a
      significant amount of bromine remains in the interstitial micropores between the
      silica particles. At around 600 degrees C, the silica nanoparticles start to fuse
      with each other and a coalescence of the micropores takes place. At still higher
      temperature, around 750 degrees C, the micropore network totally disappears, and
      the growth in pore size occurs due to the coalescence of the mesopores with a
      significant decrease of the total porosity. During this process, the silica
      network densification is accompanied by a lowering of the specific surface area.

PMID- 16584259
TI  - Electrochemically nanopatterned conducting coronas of a conjugated polymer
      precursor: SPM parameters and polymer composition.
AB  - Here we describe the formation of precisely controlled corona-type nanopatterns
      on electroactive polymer precursor films using scanning probe microscopy (SPM)
      methods. The binary composition of electroactive groups in the polymer triggers
      the formation of corona-type nanopatterns at particular voltages and tip writing
      speeds through the electrooxidation of the polymer precursor film. Various
      parameters such as tip speed and applied bias were explored in the nanopatterning
      process, and the formation of a conductive nanopattern was investigated using
      conducting atomic force microscopy (C-AFM). The formation of the nanopattern was
      attributed to the flow of electrons from the AFM tip to the polymer film in a
      controlled electric field distribution. We also report a new method to
      distinguish the polymer composition and distribution of a polymer blend film by
      characterizing biasing differences in the patterning of a polymer film.

PMID- 16584260
TI  - Self-organization of amide dendrons and their dendronized macromolecules.
AB  - A polymerizable methacryl unit was introduced at the focal moiety of the amide
      dendrons which have amide branches and alkyl periphery. Their dendronized
      polymers were also prepared by the radical polymerization of the methacryl units.
      The self-organization characteristics of dendrons and dendronized polymers were
      then investigated in both the organic and aqueous phases. The amide dendrons (1M
      and 2M) in which the focal carboxyl group was blocked with methacryl units did
      not form gel in organic media such as chloroform or THF, whereas amide dendrons
      with a free carboxyl group at the focal point form self-organized structures. In
      the aqueous phase, 1M and 2M formed spherical vesicular assemblies. The
      dendronized polymers with first and second generation dendrons, 1P and 2P,
      respectively, exhibited lamellar and columnar organization in toluene. In
      addition to hydrogen bonding between the dendritic amide branches and van der
      Waals interactions between the alkyl periphery, steric confinement of dendritic
      side groups along the polymer backbone played a key role in the packing process
      of the dendronized polymers. In aqueous phase, 1P and 2P showed spherical
      vesicular aggregates with persistent stability in the presence of Triton X-100.

PMID- 16584261
TI  - Hybrid microgels with reversibly changeable multiple brilliant color.
AB  - We report reversibly color changeable hybrid microgels that tune multiple
      brilliant colors due to interparticle interactions of SPR using several
      structured nanoparticles. The interparticle interactions were brought out using
      the thermosensitive swelling/deswelling property of microgel. We employ N
      isopropylacrylamide (NIPAM) and glycidyl methacrylate (GMA) copolymerized
      microgels (NG microgels) as templates for in situ synthesis of Au nanoparticles.
      The seed Au nanoparticles could be stably grown by successive reduction of Au and
      Ag in the microgels. Interestingly, the hybrid microgels were able to exhibit
      multiple brilliant colors by attaching Au/Ag multiple core/shell bimetallic
      nanoparticles in the microgels, and the color change reversibility of each hybrid
      microgel was accomplished by adjusting the nanoparticles' sizes. Obtained
      microgels shown in this study will find important applications such as in
      biomedical and electronic devices.

PMID- 16584262
TI  - Mechanistic studies on the conversion of dicobalt octacarbonyl into colloidal
      cobalt nanoparticles.
AB  - In situ ATR-FTIR monitoring has allowed the direct study of the effect of
      additives (trioctylphosphine oxide [TOPO] and oleic acid) on the kinetics and
      rate of the thermal decomposition of dicobalt octacarbonyl leading to the
      formation of colloidal cobalt nanoparticles (CoCNPs). The study has shown that
      additives usually considered as simple surfactants influence the rate and
      kinetics of the decomposition of dicobalt octacarbonyl. Several of the initial
      intermediates connecting Co2(CO)8 with CoCNPs have been identified, and a
      tentative mechanism for the formation of the colloidal nanoparticles has been
      proposed.

PMID- 16584263
TI  - High-quality luminescent tellurium nanowires of several nanometers in diameter
      and high aspect ratio synthesized by a poly (vinyl pyrrolidone)-assisted
      hydrothermal process.
AB  - Large-scale selective synthesis of uniform single crystalline tellurium nanowires
      with a diameter of 4-9 nm, and microbelts with a width of 250-800 nm and tens of
      micrometers in length, can be realized by a poly (vinyl pyrrolidone) (PVP)
      assisted hydrothermal process. The formation of tellurium nanowires and nanobelts
      in the presence of PVP is strongly dependent on the reaction conditions such as
      temperature, the amount of PVP, and reaction time. The results demonstrated that
      the keys for selective synthesis of Te nanobelts and nanowires are to modulate
      the growth rates of (100), (101), and (110) planes in the presence of PVP and to
      precisely control the reaction kinetics. High-quality luminescent ultrathin t-Te
      nanowires with a diameter of 4-9 nm display strong luminescent emission in the
      blue-violet region. This approach provides a facile route for the production of
      high-quality tellurium nanostructures with an interesting optical property.
      Furthermore, the synthesized ultrathin nanowires with deep blue color and
      nanobelts in gray color by this approach can be well dispersed in water or
      ethanol, making it possible for further engineering of their surfaces to prepare
      other hybrid core-shell nanostructures.

PMID- 16584264
TI  - Monte Carlo simulations of cross-linked polyelectrolyte gels with oppositely
      charged macroions.
AB  - The volume and structural changes upon replacement of oppositely charged network
      counterions for oppositely charged macroions in cross-linked polyelectrolyte gels
      have been investigated by Monte Carlo simulations using a coarse-grained model.
      Initially, the gel deswells, but after an approximately equivalent amount of
      macroions, the gel starts to swell again. The deswelling effect is greatest for
      small and highly charged macroions. The role of different network properties on
      the deswelling has also been examined. The initial deswelling is understood in
      terms of a replacement of confined counterions with macroions, thereby reducing
      the osmotic pressure originating from the counterions. At these conditions,
      macroions are located near network nodes with various degrees of network chains
      wrapping them. At charge equivalence, a profound change in the network structure
      has appeared. At these conditions, the cohesive electrostatic interaction and the
      excluded volume effect of the macroions strongly influence the equilibrium volume
      of the gel. Our model system reproduces many characteristic experimental
      observations of polyelectrolyte gels containing oppositely charged surfactants.

PMID- 16584265
TI  - Dendritic structures of poly(ethylene glycol) on silicon nitride and gold
      surfaces.
AB  - A hydrophilic silicon nitride surface was grafted with poly(ethylene glycol)
      monomethyl ether (average formula weight of 5000 Da) in a one-step protocol. The
      domains of stable dendritic structures of self-assembled monolayer islands on a
      silicon nitride surface were observed with atomic force microscopy. The moduli of
      elasticity of these dendritic structures in air and in KCl aqueous solution were
      compared. The value of the Young's modulus of these structures is reduced by more
      than 3 orders of magnitude, from approximately 12 GPa measured in air to
      approximately 5 MPa in KCl solution. This dramatic reduction in elasticity was
      attributed to the swelling of the dendritic structures in aqueous solution, which
      was verified by the increased film thickness. These dendritic structures were not
      stable in the aqueous environment and could be removed by soaking in water for 22
      h because of the hydrolysis of the silicate bonds. This fact was confirmed by the
      reduction of the C1s signal in the X-ray photoelectron spectroscopy experiments.
      These morphologies are not unique to silicon nitride substrate; similar features
      were also observed for thiolated poly(ethylene glycol) monomethyl ether molecules
      absorbed on a gold surface.

PMID- 16584266
TI  - Thermoresponsive behavior of poly(n-isopropylacrylamide) hydrogels containing
      gold nanostructures.
AB  - We report the changes in the structure and thermoresponsive behavior of poly(N
      isopropylacrylamide) (PNIPAm) hydrogels when gold nanostructures are synthesized
      in situ within the hydrogel matrix. Cross-linked PNIPAm hydrogels were
      synthesized using NIPAm and 0.00-3.50% (w/w versus NIPAm) of N,N'
      methylenebisacrylamide (MBAm) and/or N,N'-cystaminebisacrylamide (CBAm) as cross
      linking agents. The hydrogels were soaked in potassium tetrachloroaurate to
      introduce gold ions. The hydrogels containing Au3+ were then immersed in a sodium
      borohydride solution to reduce the gold ions. Infrared spectroscopy, UV-visible
      spectroscopy, and equilibrium swelling were used to examine the
      structural/physical differences between gels of different compositions; UV
      visible spectroscopy and mass measurements were used to observe the kinetics and
      thermodynamics of the hydrogel volume phase transition. These studies revealed
      several differences in the physical characteristics and thermoresponsive behavior
      of hydrogels based on cross-linker identity and the presence or absence of gold
      nanostructures. Hydrogels with gold nanostructures and high CBAm and low MBAm
      content have equilibrium swelling masses 3-20 times their native analogues. In
      comparison, gold-containing hydrogels with high MBAm and low CBAm content have
      swelling masses that are equal to their native analogues. Additionally, the gold
      containing PNIPAm hydrogels cross-linked with only CBAm have a deswelling
      temperature of approximately 40 degrees C, approximately 8 degrees C above the
      samples cross-linked with only MBAm. Varying the CBAm content and introducing
      gold enables tuning of the deswelling temperature.

PMID- 16584267
TI  - Novel and facile method for the preparation of monodispersed titania hollow
      spheres.
AB  - The fabrication of monodispersed hollow spheres in varying sizes and shapes is
      very interesting and has a lot of potential applications. This paper provides a
      very simple route to preparing hollow titania spheres using polystyrene (PS) as a
      template. In this approach, the titania shells were first formed and the PS cores
      were dissolved subsequently, even synchronously, in the same medium; neither an
      additional dissolution nor a calcination process was needed to remove the PS
      cores. Transmission electron microscopy, scanning electron microscopy, Fourier
      transform infrared spectroscopy, thermogravimetric analysis, and Barret-Emmet
      Teller measurements were used to characterize the monodispersed hollow titania
      spheres. A possible formation mechanism of the hollow spheres was proposed.

PMID- 16584268
TI  - Electrodeposition of layered manganese oxide nanocomposites intercalated with
      strong and weak polyelectrolytes.
AB  - Multilayered manganese oxide nanocomposites intercalated with strong
      (poly(diallyldimethylammonium) chloride, PDDA) and weak (poly(allylamine
      hydrochloride), PAH) polyelectrolytes can be produced on polycrystalline platinum
      electrode in a thin film form by a simple, one-step electrochemical route. The
      process involves a potentiostatic oxidation of aqueous Mn2+ ions at around +1.0 V
      (vs Ag/AgCl) in the presence of polyelectrolytes. Fully charged PDDA polycations
      are accommodated tightly in the interlayer space by electrostatic interaction
      with negative charges on the manganese oxide layers, leading to an interlayer
      distance of 0.97 nm. The layered film prepared with PAH has a larger polymer
      content (PAH/Mn molar ratio of 0.98) than that (PDDA/Mn molar ratio of 0.43) made
      with PDDA because of the smaller charging degree of PAH, exhibiting a larger
      interlayer distance (1.19 nm). The interlayer PAH contains neutral (-NH2) and
      positively charged (-NH3(+)) amine groups, and the -NH3(+) groups are associated
      with Cl- (to generate -NH3(+) Cl- ion pairs) as well as the negatively charged
      manganese oxide layers. Both polyelectrolytes once incorporated were not ion
      exchanged with small cations in solution. The layered structure of PDDA/MnO(x)
      was collapsed during the reduction process in a KCl electrolyte solution,
      accompanying an expansion of the interlayer as a result of incorporation of K+
      ions for charge neutrality. On the contrary, the layered PAH/MnO(x) film showed a
      good electrochemical response due to the redox reaction of Mn3+/Mn4+ couple with
      no change in the structure. X-ray photoelectron spectroscopy revealed that, in
      this case, excess negative charges generated on the manganese oxide layers upon
      reduction can be balanced by the protons being released from the -NH3(+) Cl-
      sites in the interlayer PAH; the Cl- anions becoming unnecessary are inevitably
      excluded from the interlayer, and vice versa upon oxidation.

PMID- 16584269
TI  - Photocatalytic decomposition of an alkylammonium cation in a Langmuir-Blodgett
      film of a titania nanosheet.
AB  - The formation of inorganic-organic hybrid films of a titania nanosheet and an
      amphiphilic alkylammonium cation has been investigated, and the photocatalytic
      decomposition of the alkylammonium cation in the film has been pursued. When a
      solution of the amphiphilic alkylammonium salt (octadecylammonium chloride: ODAH+
      Cl-) was spread on an interface between the air and a titania nanosheet
      suspension, the negatively charged nanosheets were adsorbed onto the floating
      monolayer of ODAH+ to form a hybrid monolayer. The hybridization was confirmed by
      pi-A isotherm measurements, atomic force microscopy, and X-ray photoelectron
      spectroscopy. Multilayered films were fabricated in a layer-by-layer way by
      transferring the hybrid monolayers onto glass plates. Areas per ODAH+ cation in
      the films were estimated from the infrared (IR) spectra of the films, but these
      areas were smaller than those estimated from the pi-A isotherm curves. The
      orientation of the alkyl chain of ODAH+ in the hybrid film was determined by
      means of polarized IR spectroscopy. The alkyl chains were tilted 41 +/- 1 degrees
      and 47 +/- 1 degrees from the surface normal for the films prepared from the 8
      and 20 ppm (ppm = mg dm(-3)) suspensions, respectively. Together with X-ray
      diffraction data of the films, the structure of the hybrid film was discussed.
      When the films were illuminated with a UV light, the absorption intensities due
      to the alkyl chain of ODAH+ decreased exponentially, indicating the
      photocatalytic decomposition of ODAH+ by the titania nanosheets in the films.
      Deviation from the exponential trend in the decomposition rate was observed in
      the initial period for the hybrid films prepared from the suspensions at low
      concentrations. Interestingly, the layered structure of the hybrid film was
      disturbed significantly after the ODAH+ cations were decomposed.

PMID- 16584270
TI  - Characterizing the impact of preparation method on fullerene cluster structure
      and chemistry.
AB  - We examined the physical and chemical characteristics of colloidal dispersions of
      fullerene materials (nC60) produced through several solvent exchange processes
      and through extended mixing in water only. The nC60 produced via the different
      methods were unique from each other with respect to size, morphology, charge, and
      hydrophobicity. The greatest dissimilarities were observed between the nC60
      produced by extended mixing in water alone and the nC60 produced by solvent
      exchange processes. The role of the respective solvents in determining the
      characteristics of the various nC60 were attributed to differences in the solvent
      C60 interactions and the presence of the solvent as a residual in the nC60
      structure, indicating the significance of the solvent properties in determining
      the ultimate characteristics of the colloidal fullerene. Thus, fullerene C60 that
      may become mobilized through natural processes (agitation in water) may behave in
      dramatically different ways than those produced through more artificial means.
      These results highlight the difficulties in generalizing nC60 properties,
      particularly as they vary in potential toxicity considerations.

PMID- 16584271
TI  - Tailoring the porous hierarchy of titanium phosphates.
AB  - First hierarchical titanium phosphate (TiPO) materials with multiple porosities
      of different lengths (meso-macroporous and meso-macro-macroporous) were
      synthesized by the self-formation process. The further tuning of the porous
      hierarchy by using the poly(ethylene oxide) surfactant technique was
      demonstrated. The macroporous structure (50-160 nm in size) of TiPO with
      mesoporous walls could be self-formed in the absence of any templatable agents,
      including surfactant molecules. On the basis of spontaneous structurization, the
      addition of a small quantity of nonionic poly(ethylene oxide) surfactant (e.g.,
      5%) led to an improvement in macroporosity in abundance and in regularity with a
      slight enlargement in macropore sizes to 80-250 nm. Interestingly, a secondary,
      larger macropore system with parallel channels 500-1000 nm in size was generated
      when the synthesis was performed with moderately increasing the content of
      surfactant (10%), giving rise to an unprecedented trimodal meso-macro-macroporous
      structure. A uniform three-dimensional co-continuous macroporous structure with
      accessible wormhole-like mesoporous walls was synthesized by using the higher
      content of surfactants. This is a direct demonstration of tailoring the porous
      hierarchy of different lengths integrated in one solid body by fine-tuning the
      self-formation process and the participation of surfactant. The synthesized
      hierarchical titanium phosphates possess interesting optical and acidic
      properties, which should be significant for large application potential from
      catalysis and separation to electrochromic devices, fuel cells, and bioactive
      materials.

PMID- 16584272
TI  - Dewetting of a sol-gel-derived thin film.
AB  - We report on the dewetting of a thin film produced by the sol-gel method. In the
      early stages of dynamic morphological instability, the drying stress in the
      capillary wave model determines the linearly scaling behaviors of the
      characteristic wavelength with the initial film thickness and the square law
      dependence of the number density of the dewetted holes on the film thickness.
      These power law dependences are weaker than those observed in the case of the
      spinodal dewetting of a polymer thin film. The wavelength determined in the early
      stages also dominates the scaling behaviors of the average length of the sides
      and number density of the polygons and the diameter of the droplets of the
      dewetting pattern with the film thickness in the final stages of the dynamic
      instability. We also observed that further drying eventually induces wrinkles in
      the droplets, rim, and film, which have a characteristic wavelength that can be
      theoretically predicted.

PMID- 16584273
TI  - Facile synthesis of polyaniline-sodium alginate nanofibers.
AB  - This work demonstrates a facile route to the synthesis of large quantities of
      uniform polyaniline-sodium alginate (PANI-SA) nanofibers template-guided by SA.
      This approach is an easy, inexpensive, environmentally friendly, and scalable one
      step method to produce uniform nanofibers with controllable average diameters in
      bulk quantities. We started with biopolymer-monomer complexes formed between the
      carboxylic groups of SA and the amino group of an organic monomer (aniline). When
      ammonium persulfate was added, such polymer-monomer complexes could be
      polymerized. Then, polyaniline-sodium alginate nanofibers with uniform diameters
      from 40 to 100 nm were successfully obtained in a high yield. The resultant PANI
      SA nanofibers were characterized by means of different techniques, such as
      ultraviolet-visible spectroscopy, thermogravimetric analysis, wide-angle X-ray
      diffraction, Fourier transform infrared spectroscopy, and scanning and
      transmission electron microscopy methods. The mechanism governing the formation
      of the polyaniline-sodium alginate nanofibers is discussed.

PMID- 16584274
TI  - Polymer micelles as building blocks for the incorporation of azobenzene:
      enhancing the photochromic properties in layer-by-layer films.
AB  - We described the use of block copolymer micelles as building blocks for the
      incorporation of water-insoluble photochromic species of azobenzene and the
      fabrication of multilayer films by alternating the deposition of the block
      copolymer micelles of poly(styrene-b-acrylic acid), incorporating azobenzene and
      poly(diallyl-dimethylammonium chloride). The azobenzene incorporated into the
      block copolymer micelles can undergo a reversible photoisomerization under the
      irradiation of UV and visible light sources. An interesting finding is that the
      photoisomerization of the azobenzene in the multilayer film is faster than it is
      in its normal solid film, but very similar to that in its diluted solution.
      Furthermore, the amount of azobenzene incorporated into the micelles can
      influence the photoisomerization rates in the films. Therefore, we expect that
      the block copolymer micelles may provide a proper microenvironment for the
      photoisomerization of azobenzene and the as-prepared polyelectrolyte/block
      copolymer micelle thin films will be useful for photoswitching materials.

PMID- 16584275
TI  - Transport properties and electrokinetic characterization of an amphoteric
      nanofilter.
AB  - Transport properties of a tubular nanofilter with amphoteric properties have been
      investigated by means of the SEDE (steric, electric, and dielectric exclusion)
      homogeneous model. Within the scope of this 1D model, the separation of solutes
      results from transport effects (described by means of extended Nernst-Planck
      equations) and interfacial phenomena including steric hindrance, the Donnan
      effect, and dielectric exclusion (expressed in terms of (i) the Born dielectric
      effect, which is connected to the lowering of the dielectric constant of a
      solution inside nanodimensional pores, and (ii) the interaction between ions and
      the polarization charges induced at the dielectric boundary between the pore
      walls and the pore-filling solution). The effective volume charge density of the
      membrane has been determined from tangential streaming potential experiments
      coupled with conductance experiments in a potassium chloride solution at various
      pH values ranging from 2 to 11. The inferred values have been used in the SEDE
      model to compute the ion rejection rates with the dielectric constant of the
      solution inside the pores as a single adjustable parameter. The model provides a
      relatively good description of experimental data even at extreme pH values for
      which a ternary system has been considered (K+, Cl-, and H+ or OH- depending on
      the pH). The fit to experimental data at the membrane isoelectric point indicates
      that the confinement effect decreases the dielectric constant inside the pores
      only slightly (with respect to its bulk value). However, the (pH-dependent)
      ionization of surface sites has been found to lead to a substantial lowering of
      the dielectric constant inside the pores.

PMID- 16584276
TI  - Dynamic electrophoresis of a droplet in a spherical cavity.
AB  - The electrophoretic behavior of a droplet in a spherical cavity subject to an
      alternating electric field is analyzed theoretically under the conditions of an
      arbitrary level of surface potential and double-layer thickness. The influences
      of the thickness of the double layer, the level of surface potential, the size of
      a droplet, the viscosity of the droplet fluid, and the frequency of the applied
      electric field on the electrophoretic behavior of a droplet are examined through
      numerical simulations. We show that, because of the effect of double-layer
      deformation, the magnitude of the electrophoretic mobility of a droplet could
      have a local maximum and the phase angle could have a negative (phase lead) local
      minimum as the frequency of the applied electric field varies. In general, the
      lower the surface potential, the thicker the double layer and the larger the
      viscosity of the droplet fluid, and the more significant the boundary effect, the
      smaller the magnitude of the electrophoretic mobility of a droplet.

PMID- 16584277
TI  - Surface plasmon resonance spectroscopy and electrochemistry study of 4-nitro-1,2
      phenylenediamine: a switchable redox polymer with nitro functional groups.
AB  - Electrochemistry and electrochemical surface plasmon resonance (SPR) spectroscopy
      have been applied to study the electrochemical deposition and the redox
      transition of poly(4-nitro-1,2-phenylenediamine) (P4NoPD) on gold disk. It was
      shown that SPR can be the signal transducer for the different redox states of
      P4NoPD. Using a model biomolecular system, involving streptavidin, biotinylated
      DNA, and its complementary target DNA, it was found that the presence of nitro
      groups in P4NoPD allows the biorecognition events to be modulated by voltages.
      There is minimal nonspecific binding of biomolecules on oxidized (+0.2 V) or as
      prepared P4NoPD, and binding occurs more significantly on the reduced P4NoPD (
      0.2 to -0.6 V) with the presence of amine groups. The electrochemical deposition
      of P4NoPD film was also conducted on boron-doped diamond (BDD) electrode. The
      stability of the reduced P4NoPD film on gold and BDD was comparatively evaluated
      by electrochemical impedance spectroscopy (EIS). The result showed that BDD
      allows the electrochemical reduction of the P4NoPD film at wider cathodic limits
      than gold.

PMID- 16584278
TI  - Morphology evolution of ZnO thin films from aqueous solutions and their
      application to solar cells.
AB  - This paper reports a reproducible low-temperature solution-based process for the
      preparation of ZnO films of nanorod arrays and their application to dye
      sensitized solar cells (DSSCs). A two-step approach was employed for the
      epitaxial growth of ZnO. We began with the preparation of a (002)-oriented ZnO
      seed layer by the electrochemical deposition method. After the treatment the
      substrate was soaked in an aqueous solution containing ZnCl2 and complex agents.
      A large-scale fabrication of ZnO nanorod arrays on transparent conductive oxides
      has been achieved after soaking at 95 degrees C for 1-48 h. The as-deposited ZnO
      film has a large surface area, therefore permitting a great amount of dye
      loading. The individually separated nanorod forms a linear nanoroad which should
      show more effective electron transportation than that in the film derived from
      ZnO powders. The DSSCs using these ZnO films as photoelectrodes show a conversion
      efficiency of about 0.6% at AM1.5.

PMID- 16584279
TI  - Colloidal optomagnetic dimmer.
AB  - We demonstrate a colloidal optomagnetic dimmer based on the interaction between
      micrometer-sized paramagnetic colloidal spheres and a magnetic film. The
      colloidal particles undergo Brownian motion, which when exposed to light results
      in characteristic intensity fluctuations, and we demonstrate that weak magnetic
      fields that are typically 200 A/m (2.5 G) can be used to control both the average
      intensity and the intensity fluctuations. The system can be used as a colloidal
      optical dimmer in microfluidic systems.

PMID- 16584280
TI  - Controlled release of model drugs through a molecular recognition ion gating
      membrane in response to a specific ion signal.
AB  - A controlled-release device that responds to a specific molecular signal is an
      ideal goal in drug delivery and tissue engineering. A molecular recognition ion
      gating membrane, in which a copolymer of N-isopropylacrylamide and benzo[18]
      crown-6-acrylamide was grafted onto the surface of the porous polyethylene film,
      was used to control the permeability of vitamin B12 and lysozyme in response to a
      specific ion signal. The observed response depended on the amount of grafted
      copolymer. When the grafting ratio was below 15%, the membrane pores opened by
      Ca2+ and closed by Ba2+. The permeability of model drugs became higher by opening
      of the pores. On the other hand, when the grafting ratio was above 15%, the
      properties of the membrane changed. The permeability of model drugs became lower
      by Ca2+ due to dehydration of the grafted copolymer. The opposite responses were
      observed at different grafting ratios.

PMID- 16584282
TI  - The clinical pharmacokinetics of darifenacin.
AB  - Darifenacin hydrobromide is a selective muscarinic M(3) receptor antagonist that
      is indicated for use in treatment of overactive bladder disorder. Darifenacin was
      found to have a short terminal elimination half-life after intravenous and
      immediate-release oral dosage forms (3-4 hours) but this increased with a
      prolonged-release (PR) formulation (14-16 hours). The absolute bioavailability of
      darifenacin from 7.5 and 15 mg PR tablets was estimated to be 15.4% and 18.6%,
      respectively. With repeated once-daily oral administration of the PR formulation,
      peak plasma concentrations of darifenacin are achieved approximately 7 hours post
      dose. After oral administration, darifenacin is well absorbed from the
      gastrointestinal tract and very little unchanged drug (<2%) is recovered in the
      faeces. Steady state is achieved after 6 days of once-daily administration of the
      PR formulation. As expected, values of peak plasma concentration (C(max)) and
      area under the plasma concentration-time curve are dose dependent, although the
      increase in plasma concentrations is proportionally greater than the increase in
      dose owing to saturation of presystemic metabolism. From intravenous
      administration, it has been established that darifenacin possesses a moderate-to
      high hepatic extraction ratio, with high plasma clearance (36-52 L/h) and a
      volume of distribution (165-276L) that exceeds total body water. It is highly
      protein bound (98%), primarily to alpha(1)-acid glycoprotein. Darifenacin is
      subject to extensive hepatic metabolism, with 3% of unchanged drug excreted in
      urine and faeces. Metabolism is mediated by hepatic cytochrome P450 2D6 and 3A4,
      the main metabolic routes being monohydroxylation in the dihydrobenzfuran ring,
      dihydrobenzfuran ring opening, and N-dealkylation of the pyrrolidine nitrogen.
      Several possibly important drug-drug interactions have been identified with
      darifenacin, including ketoconazole, erythromycin and fluconazole, each of which
      increases darifenacin mean C(max) by 9.52-, 2.28- and 1.88-fold, respectively.
      When given with imipramine, darifenacin causes 1.6-fold higher plasma
      concentrations of the antidepressant and its major metabolite. Moderate hepatic
      impairment, but not renal insufficiency, has been shown to increase plasma
      concentrations of the drug. The pharmacokinetic profile of darifenacin is not
      affected by food.

PMID- 16584284
TI  - Parametric and nonparametric population methods: their comparative performance in
      analysing a clinical dataset and two Monte Carlo simulation studies.
AB  - BACKGROUND AND OBJECTIVES: This study examined parametric and nonparametric
      population modelling methods in three different analyses. The first analysis was
      of a real, although small, clinical dataset from 17 patients receiving
      intramuscular amikacin. The second analysis was of a Monte Carlo simulation study
      in which the populations ranged from 25 to 800 subjects, the model parameter
      distributions were Gaussian and all the simulated parameter values of the
      subjects were exactly known prior to the analysis. The third analysis was again
      of a Monte Carlo study in which the exactly known population sample consisted of
      a unimodal Gaussian distribution for the apparent volume of distribution (V(d)),
      but a bimodal distribution for the elimination rate constant (k(e)), simulating
      rapid and slow eliminators of a drug. METHODS: For the clinical dataset, the
      parametric iterative two-stage Bayesian (IT2B) approach, with the first-order
      conditional estimation (FOCE) approximation calculation of the conditional
      likelihoods, was used together with the nonparametric expectation-maximisation
      (NPEM) and nonparametric adaptive grid (NPAG) approaches, both of which use exact
      computations of the likelihood. For the first Monte Carlo simulation study, these
      programs were also used. A one-compartment model with unimodal Gaussian
      parameters V(d) and k(e) was employed, with a simulated intravenous bolus dose
      and two simulated serum concentrations per subject. In addition, a newer
      parametric expectation-maximisation (PEM) program with a Faure low discrepancy
      computation of the conditional likelihoods, as well as nonlinear mixed-effects
      modelling software (NONMEM), both the first-order (FO) and the FOCE versions,
      were used. For the second Monte Carlo study, a one-compartment model with an
      intravenous bolus dose was again used, with five simulated serum samples obtained
      from early to late after dosing. A unimodal distribution for V(d) and a bimodal
      distribution for k(e) were chosen to simulate two subpopulations of 'fast' and
      'slow' metabolisers of a drug. NPEM results were compared with that of a unimodal
      parametric joint density having the true population parameter means and
      covariance. RESULTS: For the clinical dataset, the interindividual parameter
      percent coefficients of variation (CV%) were smallest with IT2B, suggesting less
      diversity in the population parameter distributions. However, the exact
      likelihood of the results was also smaller with IT2B, and was 14 logs greater
      with NPEM and NPAG, both of which found a greater and more likely diversity in
      the population studied. For the first Monte Carlo dataset, NPAG and PEM, both
      using accurate likelihood computations, showed statistical consistency.
      Consistency means that the more subjects studied, the closer the estimated
      parameter values approach the true values. NONMEM FOCE and NONMEM FO, as well as
      the IT2B FOCE methods, do not have this guarantee. Results obtained by IT2B FOCE,
      for example, often strayed visibly away from the true values as more subjects
      were studied. Furthermore, with respect to statistical efficiency (precision of
      parameter estimates), NPAG and PEM had good efficiency and precise parameter
      estimates, while precision suffered with NONMEM FOCE and IT2B FOCE, and severely
      so with NONMEM FO. For the second Monte Carlo dataset, NPEM closely approximated
      the true bimodal population joint density, while an exact parametric
      representation of an assumed joint unimodal density having the true population
      means, standard deviations and correlation gave a totally different picture.
      CONCLUSIONS: The smaller population interindividual CV% estimates with IT2B on
      the clinical dataset are probably the result of assuming Gaussian parameter
      distributions and/or of using the FOCE approximation. NPEM and NPAG, having no
      constraints on the shape of the population parameter distributions, and which
      compute the likelihood exactly and estimate parameter values with greater
      precision, detected the more likely greater diversity in the parameter values in
      the population studied. In the first Monte Carlo study, NPAG and PEM had more
      precise parameter estimates than either IT2B FOCE or NONMEM FOCE, as well as much
      more precise estimates than NONMEM FO. In the second Monte Carlo study, NPEM
      easily detected the bimodal parameter distribution at this initial step without
      requiring any further information. Population modelling methods using exact or
      accurate computations have more precise parameter estimation, better stochastic
      convergence properties and are, very importantly, statistically consistent.
      Nonparametric methods are better than parametric methods at analysing populations
      having unanticipated non-Gaussian or multimodal parameter distributions.

PMID- 16584283
TI  - Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes
      of age.
AB  - In recent years, several new-generation antiepileptic drugs (AEDs) have been
      introduced in clinical practice. These agents, which include felbamate,
      gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine,
      topiramate, vigabatrin and zonisamide, are being increasingly used in the
      treatment of epilepsy at the extremes of age. For a rational prescribing of these
      drugs in specific age groups, major pharmacokinetic changes that occur during
      development and aging need to be taken into consideration. A review of available
      evidence indicates that the apparent oral clearance (CL/F) of new-generation AEDs
      in children is increased by 20-170% (depending on the type of drug and
      characteristics of the patients studied) compared with adults, with the highest
      CL/F values usually being observed in the youngest age groups. These findings do
      not necessarily apply to the first weeks of life, when drug eliminating capacity
      is still undergoing maturation, as in the case of lamotrigine for which
      preliminary data suggest that CL/F in neonates aged <2 months can be much lower
      than in infants aged 2-12 months. At the other extreme of age, in the elderly,
      CL/F is almost invariably reduced (on average by 10-50%) compared with values
      found in non-elderly adults. Age-related CL/F changes, together with the large
      interindividual pharmacokinetic variability, contribute to the need for
      individualised dosage requirements in these patients. Measurement of serum drug
      concentrations can be useful as an aid to dosage individualization in these age
      groups but interpretation of therapeutic drug monitoring data should also take
      into account the possibility of age-related changes in pharmacodynamic
      sensitivity and, for neonates and the elderly, alterations in drug binding to
      serum proteins.

PMID- 16584285
TI  - Feasibility of biowaiver extension to biopharmaceutics classification system
      class III drug products: cimetidine.
AB  - BACKGROUND: The extension of biowaivers (drug product approval without a
      pharmacokinetic bioequivalence study) to drugs belonging to Class III of the
      Biopharmaceutics Classification System (BCS) is currently a subject of much
      discussion. OBJECTIVES: To assess the relationship between in vitro dissolution
      characteristics and in vivo absorption performance of immediate-release (IR)
      products containing cimetidine, a BCS Class III compound, in human subjects. To
      evaluate the feasibility and appropriateness of an extension of the biowaiver
      concept to BCS Class III compounds. STUDY DESIGN AND PARTICIPANTS: BCS-conform
      dissolution tests were carried out on ten marketed cimetidine products from
      Thailand and Germany, as well as cimetidine tablet formulations containing
      cimetidine 400mg manufactured by direct compression using methacrylate copolymer
      (Eudragit) RS PO) as a release-retarding agent to yield three batches with
      significantly different release profiles. Twelve healthy male subjects were
      enrolled in a randomised, open-label, single-dose schedule based on a five-way
      Williams' design balanced for carryover effects. Subjects received the following
      treatments, with 1-week washout periods between: (i) Tagamet 400mg tablet; (ii)
      7.5% methacrylate copolymer cimetidine tablet; (iii) 15% methacrylate copolymer
      cimetidine tablet; (iv) 26% methacrylate copolymer cimetidine tablet; and (v)
      Tagamet (300 mg/ 2 mL) intravenous injection. The area under the plasma
      concentration-time curve from 0 to 12 hours (AUC(12)) and AUC from time zero to
      infinity (AUC(infinity)), peak plasma concentration (C(max)), absolute
      bioavailability (F) and mean residence time (MRT) were evaluated and
      statistically compared among formulations. In vitro-in vivo correlation (IVIVC)
      analysis was then applied to elucidate the overall absorption characteristics of
      each tablet formulation. RESULTS: The release properties of the ten marketed
      cimetidine products were shown to comply with current US FDA criteria for rapidly
      dissolving drug products. As expected, the in vitro dissolution profiles of the
      cimetidine tablets containing different percentages of methacrylate copolymer
      differed considerably from one another. However, in vivo results showed no
      significant difference in AUC(12), AUC(infinity), C(max) and F between the
      tablets manufactured with methacrylate copolymer and the innovator. The MRT
      values obtained from 26% methacrylate copolymer tablets were significantly longer
      than for the other two methacrylate copolymer formulations and the Tagamet
      tablets. Furthermore, IVIVC analysis showed that the 26% methacrylate copolymer
      tablets exhibited dissolution rate-limited absorption, whereas the other
      formulations showed permeability rate-limited absorption. CONCLUSION: The results
      of the present study indicated that the absorption of cimetidine from IR tablets
      is, in general, limited by permeability rather than dissolution. IVIVC analysis
      demonstrated that only when the release was deliberately retarded (tablets
      containing 26% methacrylate copolymer), did the dissolution represent the rate
      limiting step to drug absorption. On the in vitro side, it seems that 85%
      dissolution within 30 minutes, as currently required by the US FDA Guidance, is
      more than sufficient to guarantee bioequivalence of IR cimetidine products. For
      cimetidine and other BCS Class III drugs with a similar intestinal absorption
      pattern, application of the biowaiver concept seems to present little risk of an
      inappropriate bioequivalence decision.

PMID- 16584286
TI  - Population pharmacokinetics of heroin and its major metabolites.
AB  - BACKGROUND: In several European countries and in Canada, clinical trials are
      being conducted in which heroin-addicted patients are treated with
      pharmaceutically prepared heroin in order to reduce the destructive behaviour
      that is so often associated with this drug. OBJECTIVE: To develop an integrated
      population pharmacokinetic model for heroin (diamorphine) and its
      pharmacodynamically active metabolites 6-acetylmorphine, morphine, morphine-3
      glucuronide and morphine-6-glucuronide. Additionally, the influence on heroin
      pharmacokinetics of several covariates that are typical for this population was
      determined. METHOD: Plasma concentration data from 106 heroin-dependent patients
      in The Netherlands (74 heroin inhalers and 32 injectors) were obtained. The
      'chasing the dragon' technique was used for inhalation, in which the fumes of
      heroin base, heated on aluminum foil, were inhaled. Heroin doses varied between
      66 and 450 mg. Heroin, 6-acetylmorphine and morphine data were fitted
      simultaneously using sequential two-compartment models. Morphine-3-glucuronide
      and morphine-6-glucuronide data were fitted separately to one-compartment models.
      All data analysis was performed using nonlinear mixed-effect modelling. RESULTS:
      The bioavailability of inhaled heroin was estimated to be 53% (95% CI 43.7,
      62.3). The terminal half-lives of heroin and 6-acetylmorphine were estimated to
      be 7.6 and 21.8 minutes, respectively. The clearances of morphine and the
      morphine-glucuronides were estimated to be 73.6 L/h (95% CI 62.8, 84.4) and
      between 6 and 10 L/h, respectively. The terminal half-life of 6-acetylmorphine
      was 13% lower in cocaine users (p < 0.05). No other significant relationships
      between covariates and pharmacokinetic parameters were discovered. CONCLUSIONS:
      Pharmacokinetic parameters of heroin and its five major metabolites were assessed
      simultaneously in one integrated model. Covariate analyses revealed that sex,
      bodyweight, benzodiazepine use and creatinine clearance (>60 mL/min) do not need
      to be taken into account in the medical prescription of pharmaceutically prepared
      heroin for the treatment of heroin dependency.

PMID- 16584287
TI  - Placental transfer of ondansetron during early human pregnancy.
AB  - BACKGROUND AND OBJECTIVE: Nausea and vomiting are common conditions that occur
      during early pregnancy and can be disabling. Ondansetron had been used in
      pregnant women when treatment with conventional antiemetics has failed; however,
      the safety and tolerability of this relatively new antiemetic drug during
      pregnancy is still uncertain. The objective of this study was to quantify the
      placental transfer of ondansetron in the first trimester of human pregnancy.
      PATIENTS AND METHODS: This was a prospective, observational study. Forty-one
      patients who requested surgical termination of pregnancy at the first trimester
      were administered three doses of ondansetron 8 mg before surgery. Maternal venous
      blood, coelomic fluid, amniotic fluid and fetal tissue were collected from each
      patient for analysis of ondansetron by liquid chromatography-mass spectometry.
      RESULTS: Ondansetron was found in all samples. Drug concentration in fetal tissue
      was significantly higher than that in the amniotic fluid and similar to that in
      the coelomic fluid. The median (interquartile range) fetal/maternal ratio was
      0.41 (0.31-0.52) and there were no significant correlations between ondansetron
      concentrations in each compartment and gestational age. CONCLUSIONS: A
      significant amount of ondansetron was present in all embryonic compartments. The
      developmental significance of this drug exposure requires further investigation,
      i.e. whole embryo culture.

PMID- 16584288
TI  - The effects of food on the bioavailability of fenofibrate administered orally in
      healthy volunteers via sustained-release capsule.
AB  - OBJECTIVE: To examine the effects of food on plasma concentration and
      bioavailability of fenofibrate administered as a sustained-release capsule.
      METHODS: Twenty-four healthy Korean volunteers were enrolled in a randomised,
      open-label, balanced, three-treatment, three-period, three-sequence, single oral
      dose, crossover pharmacokinetic study. A single dose of fenofibrate (250 mg
      sustained-release capsule) was administered on three occasions -- after overnight
      fasting, after consumption of a standard breakfast and after a high-fat
      breakfast. Serial blood samples were collected for the next 72 hours. Plasma
      fenofibric acid concentrations were measured by high-performance liquid
      chromatography, and pharmacokinetic parameters were calculated. RESULTS: The
      pharmacokinetic parameters were significantly affected by food intake. The high
      fat breakfast affected the rate of absorption of fenofibrate more than the
      standard breakfast and fasted conditions. Specifically, the area under the plasma
      concentration-time curve from time zero to infinity (AUC(infinity)) and peak
      plasma concentration (C(max)) increased 2.45-fold and 2.89-fold, respectively,
      between the fasted and standard-fed conditions (p < 0.01). In addition, the high
      fat meal caused 3.34-fold and 3.82-fold increases compared with the fasted
      condition in AUC(infinity) and C(max), respectively. A one-compartment open model
      with lag time successfully described the plasma concentrations of fenofibric
      acid. CONCLUSION: In healthy volunteers, AUC(infinity) and C(max) of fenofibrate,
      when administered via sustained-release capsules immediately after the
      consumption of food, was increased significantly from the fasting conditions (p <
      0.01). The greatest AUC(infinity) and C(max) occurred when the capsules were
      taken after a high-fat breakfast.

PMID- 16584291
TI  - Adenovirus-delivered antisense RNA and shRNA exhibit different silencing
      efficiencies for the endogenous transforming growth factor-beta (TGF-beta) type
      II receptor.
AB  - Gene silencing is an essential tool in gene discovery and gene therapy.
      Traditionally, viral delivery of antisense RNA and, more recently, small
      interfering RNA (siRNA) molecules in the form of small hairpin RNAs (shRNA) has
      been used as a strategy to achieve gene silencing. Nevertheless, the enduring
      challenge is to identify molecules that specifically and optimally silence a
      given target gene. In this study, we tested a set of adenovirus-delivered
      antisense RNA fragments and adenovirus-delivered shRNA molecules for their
      ability to target human transforming growth factor-beta type II receptor
      (TGFbetaRII). We used a dicistronic reporter, consisting of the coding sequences
      for TGFbetaRII and green fluorescent protein (GFP) to screen for optimal
      silencing agents targeting TGFbetaRII. Our results show, for both antisense RNA
      and shRNA molecules, that their effectiveness in the GFP screen correlated
      directly with their ability to reduce exogenously expressed TGFbetaRII.
      Unexpectedly, the antisense RNAs were unable to silence endogenous TGFbetaRII. In
      contrast, the shRNAs were able to silence endogenous TGFbetaRII. The shRNA that
      demonstrated the most pronounced effect on the dicistronic TGFbetaRII/GFP
      reporter reduced endogenous TGFbetaRII protein expression by 70% in A549 cells
      and reduced TGFbeta signaling by >80% in HeLa cells.

PMID- 16584289
TI  - Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2.
AB  - BACKGROUND: Streptococcus suis serotype 2 (S. suis 2, SS2) is a major zoonotic
      pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most
      if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well
      documented to date were associated with the non-SS2 group A streptococcus (GAS).
      However, a recent large-scale outbreak of SS2 in Sichuan Province, China,
      appeared to be caused by more invasive deep-tissue infection with STSS,
      characterized by acute high fever, vascular collapse, hypotension, shock, and
      multiple organ failure. METHODS AND FINDINGS: We investigated this outbreak of
      SS2 infections in both human and pigs, which took place from July to August,
      2005, through clinical observation and laboratory experiments. Clinical and
      pathological characterization of the human patients revealed the hallmarks of
      typical STSS, which to date had only been associated with GAS infection.
      Retrospectively, we found that this outbreak was very similar to an earlier
      outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37
      bacterial strains from human specimens and eight from pig specimens of the recent
      outbreak, as well as three human isolates and two pig isolates from the 1998
      outbreak we had kept in our laboratory. The bacterial isolates were examined
      using light microscopy observation, pig infection experiments, multiplex-PCR
      assay, as well as restriction fragment length polymorphisms (RFLP) and multiple
      sequence alignment analyses. Multiple lines of evidence confirmed that highly
      virulent strains of SS2 were the causative agents of both outbreaks. CONCLUSIONS:
      We report, to our knowledge for the first time, two outbreaks of STSS caused by
      SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out
      of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25
      reported human cases. Most of the fatal cases were characterized by STSS; some of
      them by meningitis or severe septicemia. The molecular mechanisms underlying
      these human STSS outbreaks in human beings remain unclear and an objective for
      further study.

PMID- 16584292
TI  - Inhibition of human carcinoma and neuroblastoma cell proliferation by anti-c-myc
      siRNA.
AB  - Suppression of c-myc proto-oncogene expression by small interfering RNA (siRNA)
      in human epidermoid carcinoma KB-3-1 and neuroblastoma SK-N-MC cell lines was
      investigated. The siRNA duplex targeted to the exon 3 of c-myc mRNA (siRNA-I) was
      prepared by in vitro transcription using T7 RNA polymerase and short double
      stranded DNA (dsDNA) templates. siRNA-I was shown to efficiently decrease c-myc
      mRNA expression in both tumor cell lines and to arrest their proliferation.
      Incubation of KB-3-1 cells with 150 nM siRNA-I results in a 92% decrease in the c
      myc mRNA level and an 83% decrease in the protein level. In SK-N-MC cells, 150 nM
      siRNA-I causes a 60% decrease in the c-myc mRNA level and a 55% decrease in the
      protein level. The reduction of the c-myc mRNA level correlates with the
      inhibition of cell proliferation; 150 nM siRNA-I causes a 2.5-fold reduction in
      the SK-N-MC proliferation rate and a 15-fold decrease in the proliferation rate
      and complete arrest of cell division in KB-3-1 cells. siRNA-I has little effect
      on proliferation of the IMR-32 cells that overexpress the N-myc but not the c-myc
      gene, demonstrating that siRNA-I antiproliferation activity is mediated by
      specific block of c-myc expression.

PMID- 16584293
TI  - Characterization of modified antisense oligonucleotides in Xenopus laevis
      embryos.
AB  - A wide variety of modified oligonucleotides have been tested as antisense agents.
      Each chemical modification produces a distinct profile of potency, toxicity, and
      specificity. Novel cationic phosphoramidate-modified antisense oligonucleotides
      have been developed recently that have unique and interesting properties. We
      compared the relative potency and specificity of a variety of established
      antisense oligonucleotides, including phosphorothioates (PS), 2'-O-methyl (2'OMe)
      RNAs, locked nucleic acids (LNAs), and neutral methoxyethyl (MEA)
      phosphoramidates with new cationic N,N-dimethylethylenediamine (DMED)
      phosphoramidate-modified antisense oligonucleotides. A series of oligonucleotides
      was synthesized that targeted two sites in the Xenopus laevis survivin gene and
      were introduced into Xenopus embryos by microinjection. Effects on survivin gene
      expression were examined using quantitative real-time PCR. Of the various
      modified oligonucleotide designs tested, LNA/PS chimeras (which showed the
      highest melting temperature) and DMED/phosphodiester chimeras (which showed
      protection of neighboring phosphate bonds) were potent in reducing gene
      expression. At 40 nM, overall specificity was superior for the LNA/PS-modified
      compounds compared with the DMED-modified oligonucleotides. However, at 400 nM,
      both of these compounds led to significant degradation of survivin mRNA, even
      when up to three mismatches were present in the heteroduplex.

PMID- 16584294
TI  - Evaluation of transfection protocols for unmodified and modified peptide nucleic
      acid (PNA) oligomers.
AB  - We have compared the efficacy of different transfection protocols reported for
      peptide nucleic acid (PNA) oligomers. A precise evaluation of uptake efficacy was
      achieved by using a positive readout assay based on the ability of a PNA oligomer
      to correct aberrant splicing of a recombinant luciferase gene. The study
      comprised transfection of PNA conjugated to acridine, adamantyl, decanoic acid,
      and porphyrine (acr-PNA, ada-PNA, deca-PNA, and por-RNA, respectively) and
      unmodified PNA partially hybridized to a DNA oligomer (PNA/DNA cotransfection).
      Furthermore, the effect of conjugation to a nuclear localization signal (NLS) was
      evaluated as part of the PNA/DNA cotransfection protocol. Transfection of the
      tested PNAs was systematically optimized. PNA/DNA cotransfection was found to
      produce the highest luciferase activity, but only after careful selection of the
      DNA oligonucleotide. Both a cationic lipid, Lipofectamine, and a nonliposomal
      cationic polymer, polyethylenimine (PEI, ExGen 500), were efficient transfection
      reagents for the PNA/DNA complex. However, Lipofectamine, in contrast to PEI,
      showed severe side effects, such as cytotoxicity. acr-PNA, ada-PNA, and por-PNA
      were transfectable with efficacies between 5 and 10 times lower than that seen
      with PNA/DNA cotransfection. Conjugation of PNA to NLS had no effect on PNA/DNA
      cotransfection efficacy. An important lesson from the study was the finding that
      because of uncontrollable biologic variations, even optimal transfection
      conditions differed to a certain extend from experiment to experiment in an
      unpredictable way.

PMID- 16584295
TI  - Stimulation of innate immune responses by CpG oligodeoxynucleotide in newborn
      lambs can reduce bovine herpesvirus-1 shedding.
AB  - Stimulation of the innate immune system is potentially very important in neonates
      who have an immature adaptive immune system and vaccination cannot be used to
      reduce the risk of infection. CpG oligodeoxynucleotide (ODN) can stimulate innate
      immune responses in newborn chickens and mice, but similar studies are lacking in
      other mammalian species. We have shown previously that CpG ODN can both stimulate
      an acute-phase immune response and induce the antiviral effector molecule, 2'5'-A
      synthetase, in adult sheep. Therefore, the immunostimulatory activity of A class
      and B class CpG ODN was evaluated in newborn lambs, and the capacity of CpG ODN
      induced responses to reduce viral shedding was evaluated following aerosol
      challenge with the respiratory pathogen, bovine herpesvirus-1 (BHV-1). In vitro
      CpG ODN stimulation of peripheral blood mononuclear cells (PBMC) isolated from
      newborn lambs (3-5 days old) and adult sheep induced equivalent CpG-specific
      proliferative responses and interferon-alpha (IFN-alpha) secretion. CpG ODN
      induced IFN-alpha secretion by neonatal PBMCs was, however, significantly (p <
      0.01) enhanced 6 days after subcutaneous (s.c.) injection of 100 microg/kg CpG
      ODN 2007. Newborn lambs injected s.c. with B class CpG ODN 2007 or the inverted
      GpC control ODN formulated in 30% Emulsigen (MVP Laboratories, Ralston, NE)
      displayed CpG ODN-specific increases in body temperature (p < 0.0001), serum 2'5'
      A synthetase activity (p = 0.0015), and serum haptoglobin (p = 0.07). CpG ODN
      treated lambs also displayed a transient reduction in viral shedding on day 2
      postinfection (p < 0.05), which correlated (p < 0.03) with serum 2'5'-A
      synthetase levels on the day of viral challenge. These observations confirmed
      that CpG ODNs effectively activate innate immune responses in newborn lambs and
      CpG ODN-induced antiviral responses correlated with a reduction in viral
      shedding.

PMID- 16584296
TI  - A novel class of DNA analogs bearing 5'-C-phosphonothymidine units: synthesis and
      physicochemical and biochemical properties.
AB  - S(C) and R(C) diastereomers of 5'-C-(O,O-diethyl)-phosphonylthymidine ((R)T and
      (S)T) were used for the synthesis of the dimers T(R)T and T(S)T, respectively.
      These dimers were incorporated at selected sites in oligonucleotide constructs.
      Melting temperature (Tm) experiments demonstrated that relative to the unmodified
      oligodeoxyribonucleotide, the presence of the (R)T moiety reduced the thermal
      stability of the duplexes by approximately 5.0 degrees C per modification,
      whereas their (S)T counterparts only slightly destabilized the duplex structure
      (deltaTm < or = 1 degree C/modification). The stability of the triple-helical
      complexes containing one, two, or three modified thymidines is slightly higher
      than that of the parent complex. Nuclease resistance studies performed with snake
      venom phosphodiesterase, calf spleen phosphodiesterase, and 3'-exonuclease from
      human plasma showed that cleavage of the oligonucleotides at the site of the
      modification was completely suppressed regardless of the stereochemistry of the
      5'-C-chiral center. The influence of the (R)T and (S)T modification in the
      recognition sequence of HindIII, EcoRI, and HpaI restriction endonucleases was
      also investigated. Although the catalytic activity of HindIII was not affected by
      the presence of the 5'-C-ethoxyphosphonyl modification, the activities of the two
      remaining restriction enzymes were partially suppressed depending on the site of
      modification or the stereochemistry of the modification or both ((R)T vs. (S)T).

PMID- 16584298
TI  - Involvement of ERCC1/XPF and XPG in oligodeoxynucleotide-directed gene
      modification.
AB  - Oligodeoxynucleotide (ODN)-mediated gene alteration was postulated to occur in
      two steps, DNA strand pairing and DNA repair. Once alignment has occurred through
      homologous strand pairing, a single mismatch is formed between an oligonucleotide
      and one of the target strands. Because of this mismatch, it has been suggested
      that proteins involved in a mismatch repair pathway (MMR) participate in the
      process. We proposed an alternative model, in which a transient assimilation of
      ODN to the target DNA can interrupt the trafficking of RNA polymerase, and the
      stalled RNA polymerase may signal for recruitment of DNA repair proteins,
      including transcription-coupled (TCR) DNA repair and nucleotide excision repair
      (NER) pathways. Recently, we found that transcription of many genes participating
      in NER and MMR was induced by the presence of plasmid DNA, and the extent of
      induction correlated with episomal gene repair rates. To investigate whether an
      increased level of induction of genes involved in specific DNA repair pathways
      has a functional role in ODN-directed gene repair, we performed episomal
      targeting in several cell lines with a specific defective gene in NER and MMR
      pathways. Comparison among several genetically related cell lines harboring a
      specific defective gene and complementation of missing activities showed that a
      primary pathway for gene correction involves some of the proteins participating
      in NER, primarily two endonucleases processing a DNA lesion, but not MMR.

PMID- 16584299
TI  - Defibrotide, a polydisperse mixture of single-stranded phosphodiester
      oligonucleotides with lifesaving activity in severe hepatic veno-occlusive
      disease: clinical outcomes and potential mechanisms of action.
AB  - Veno-occlusive disease of the liver (VOD) remains a troubling and potentially
      fatal complication of high-dose chemotherapy and hematopoietic stem cell
      transplantation conditioning regimens. No effective therapy has been available
      for these patients to date, and the best supportive care measures remain woefully
      inadequate. Defibrotide (DF) (Gentium, S.p.A., Como, Italy), a polydisperse
      mixture of all the single-stranded phosphodiester oligodeoxyribonucleotides that
      can be obtained from the controlled depolymerization of porcine intestinal
      mucosal genomic DNA, seems to offer a safe and effective treatment for some
      patients suffering from severe VOD, a condition for which no accepted standard
      therapy currently exists. Early clinical studies evaluating the efficacy of DF
      for the treatment of severe VOD in patients undergoing hematopoietic stem cell
      transplantation have been very encouraging. Approximately 45% of the patients
      treated in multiple initial phase II clinical trials achieved a complete response
      at day +100, demonstrating normalization of serum bilirubin and resolution of the
      clinical syndrome. However, although multi-institutional, these represented
      single arm studies. A large, FDA-approved, pivotal, prospective, multi
      institutional, global phase III trial of DF vs. historical controls (best
      available therapy) commenced in the first quarter of 2006 and should provide
      further validation of DF's efficacy. The drug seems to have few significant side
      effects, and almost all test subjects who have received this treatment have
      tolerated it well. Although the mechanism of action remains unclear, the drug
      exerts minimal systemic anticoagulant effects yet appears to induce numerous
      antithrombotic and profibrinolytic effects both in vitro and in vivo. It may
      function as an adenosine receptor agonist and causes increased concentrations of
      endogenous prostaglandins, which modulate thrombomodulin, platelets, and
      fibrinolysis. It also appears to block lipopolysaccharide (LPS)-induced tissue
      factor (TF) expression. However, despite the fact the DF is composed of
      oligonucleotides, its mechanism of action, which at the present time is unclear,
      is not related to Watson-Crick base pair-dependent downregulation of gene
      expression but is rather likely a result of its polyanionic nature.

PMID- 16584297
TI  - G3139 and other CpG-containing immunostimulatory phosphorothioate
      oligodeoxynucleotides are potent suppressors of the growth of human tumor
      xenografts in nude mice.
AB  - Several phosphorothioate antisense oligodeoxynucleotides (ODN) are developed to
      target factors potentially involved in tumor growth and apoptosis suppression.
      Among them, the 18-mer G3139 (Oblimersen), which targets Bcl-2, is currently
      being tested in phase II and phase III clinical trials for various tumors in
      combination with chemotherapy. On the other hand, ODNs containing CpG
      dinucleotides (CpG-ODN) within specific-sequence contexts (CpG motifs) have been
      shown to activate rodent or primate immune cells via toll-like receptor 9 (TLR9)
      and have demonstrated remarkable T cell-dependent antitumor efficacy in a series
      of murine tumor models. However, immune cell activation by CpG-ODN is largely
      diminished upon C-5 methylation at CpG cytosine. As G3139 contains CpG motifs, we
      questioned whether the antitumor effects seen in human tumor xenografts might be
      abrogated by cytosine C-5 methylation of G3139, which retained the ability of
      G3139 to suppress Bcl-2 expression in tissue culture, or by similar
      derivatization of other phosphorothioate ODNs developed for the immune activation
      of rodent or human cells. The in vivo antitumor efficacy of the immunostimulatory
      H1826 and H2006 ODNs was compared with that of G3139. Bcl-2 suppression achieved
      by G3139 purportedly sensitizes tumor cells toward cytotoxic agents, and some of
      the experiments employed combinations of ODN with such drugs as cisplatin or
      etoposide. H1826, H2006, and G3139 all produced similar, striking, growth
      inhibitory effects on either H69 SCLC, A2780 ovarian carcinoma, or A549 lung
      adenocarcinoma human tumor xenografts at doses of 0.3 mg/kg and 1 mg/kg (H1826,
      H2006) or 12 mg/kg (G3139) per day. In contrast, the H2006-mC (1 mg/kg) or G3139
      mC (12 mg/kg) derivatives demonstrated no significant antitumor effects. The
      combination of G3139 (12 mg/kg) with cisplatin produced some additive antitumor
      efficacy, which was not seen in combinations of G3139-mC (12 mg/kg) or H1826 (1
      mg/kg) with cisplatin. G3139, at a dose of 12 mg/kg, alone induced extensive
      enlargement of the spleen. Immunostimulation was evaluated in vitro by flow
      cytometric measurements of the CD80 and CD86 activation markers found on CD19+
      murine splenocytes. The CpG-ODN producing strong antitumor effects in vivo also
      induced these activation markers in vitro, in contrast to the in vivo inactive
      G3139-mC. Our data indicate a significant contribution of the immunostimulatory
      properties of CpG-ODN (including G3139) to the antitumor effects observed in nude
      mouse xenograft models. This is in contrast to previous data presented by other
      authors indicating that the activity of G3139 in human tumor xenografts was Bcl-2
      specific. Furthermore, as nude mice are devoid of T cells, a T cell-mediated
      immune response apparently is not required for the potent antitumor responses
      observed here; innate immune responses are sufficient.

PMID- 16584300
TI  - In vivo efficacy of phage therapy for Mycobacterium avium infection as delivered
      by a nonvirulent mycobacterium.
AB  - The emergence of mycobacteria resistant to currently available antimicrobial
      agents has become an important problem in modern medicine. Mycobacterium avium
      and M. tuberculosis are intracellular pathogens that replicate and survive within
      the mononuclear phagocytes. TM4 is a lytic mycobacteriophage that kills both
      extracellular M. avium and M. tuberculosis. When delivered by M. smegmatis
      transiently infected with TM4, it kills both M. avium and M. tuberculosis within
      RAW 264.7 macrophages. To evaluate the treatment of M. avium infection with phage
      in vivo, C57 BL/6 mice were infected with M. avium 109 and, 7 days later, treated
      either once or twice with TM4 phage (7.9 x 10(10) PFU/ml), M. smegmatis (4 x
      10(8) cFU/ml), or M. smegmatis with TM4 phage delivered intravenously (i.v.).
      Treatment with TM4 phage alone or M. smegmatis without TM4 did not show a
      significant decrease in number of intracellular bacteria in the spleen compared
      with untreated control. In contrast, administration of M. smegmatis-TM4 resulted
      in a significant decrease in the number of M. avium in the spleen. However, 23%
      of bacteria recovered from treated mice were resistant to TM4. These in vivo
      studies confirmed the in vitro findings that an avirulent mycobacterium can be
      used as a carrier to deliver antimycobacterial phage intracellularly.

PMID- 16584301
TI  - Stepwise decrease in moxifloxacin susceptibility amongst clinical isolates of
      multidrug-resistant Mycobacterium tuberculosis: correlation with ofloxacin
      susceptibility.
AB  - To study the effectiveness of moxifloxacin (MOX) against multidrug-resistant
      (MDR) Mycobacterium tuberculosis (MTB), in vitro drug susceptibility tests on MOX
      and ofloxacin (OFX) using the MGIT system against 132 nonduplicate MDR MTB
      isolates (108 OFX-sensitive and 24 OFX-resistant) were performed. Eleven OFX
      resistant non-MDR MTB isolates were also included. All strains that were
      susceptible to OFX were shown to be also susceptible to MOX. For OFX-resistant
      isolates, regardless of their MDR status, a 4- to 8-fold decrease in MIC was
      observed for MOX when compared to OFX. On the basis of similarities in mode of
      action and pharmacokinetic data between MOX and OFX, a breakpoint MIC of 2 mg/L
      was suggested for MOX in the MGIT system. All but two OFX-resistant isolates
      possessed MIC of MOX of 2 mg/L or lower and were considered to be susceptible to
      MOX; however, all OFX-resistant strains studied had mutations involved in
      resistance to quinolones. DNA sequence analysis for the gyrase A mutation, which
      was an indicator for OFX resistance, correlated with MOX susceptibility changes.
      Significant decreases in MOX susceptibility amongst MDR-MTB strains were observed
      that correlated with OFX susceptibility. The Asp94Gly mutation appeared to be
      associated with a higher level of MICs to both OFX and MOX. These findings on the
      stepwise decline of in vitro susceptibility to MOX suggest that clinical usage of
      MOX should be accompanied by careful monitoring of susceptibility to this
      important anti-MDR MTB drug.

PMID- 16584302
TI  - Extended-spectrum beta-lactamase genes of Klebsiella pneumoniae strains in
      Taiwan: recharacterization of shv-27, shv-41, and tem-116.
AB  - Klebsiella pneumoniae causing primary liver abscess (PLA) is emerging. This study
      identified the beta-lactamases genes of K. pneumoniae isolates in Taiwan. The
      susceptibilities of beta-lactam antibiotics of 30 K. pneumoniae strains
      associated with primary liver abscess and 30 noninvasive strains were analyzed.
      The beta-lactamase genes of randomly selected 24 strains from community-acquired
      infection and 7 extended-spectrum beta-lactamases (ESBL) strains were identified
      by PCR and DNA sequencing. Protein expression and the ESBL phenotype of beta
      lactamase were determined. All 60 strains were ampicillin resistant and
      cefotaxime susceptible, whereas no strain was ESBL producing. In the 24 selected
      strains, shv-1a was found in 14, shv-1 in 7; shv-26, shv-27, and shv-41 were
      detected in one. However, all of these 24 strains had the tem-116 gene. In 7 ESBL
      producing K. pneumoniae strains, shv-5a was found in 5, whereas shv-5 and ctx-m-9
      group were detected in 1 strain. Two previously reported ESBL genes, shv-27 and
      tem-116, as well as a suspected ESBL gene, shv-41, were found in non-ESBL
      producing strains. Transformation of these genes conferred ampicillin resistance
      but not the ESBL-producing phenotype in Escherichia coli. Beta-lactamase protein
      expression of these strains was further confirmed by western blotting. In
      conclusion, ESBL is rare in community-acquired K. pneumoniae infection and is not
      associated with PLA in Taiwan. The shv-5a, shv-5, and ctx-m-9 groups are present
      in ESBL-producing strains in Taiwan, but shv-27, shv-41, and tem-116 are not ESBL
      genes.

PMID- 16584303
TI  - Penicillin-resistant pneumococci in Sweden 1997-2003: increased multiresistance
      despite stable prevalence and decreased antibiotic use.
AB  - Antimicrobial resistance patterns and capsular groups of penicillin-resistant
      Streptococcus pneumoniae (PRP; MIC penicillin G > or = 0.5 mg/ml) in Sweden
      between 1997 and 2003 were described, and trends in resistance and antibiotic
      sales during the same period were compared. The most common serogroups were in
      descending order 9, 19, 14, 23, and 6. Despite a low and stable annual PRP rate
      (proportion of PRP out of all pneumococci) of around 2% during the study period,
      the proportion of PRP resistant to other antibiotics increased. Of all tested PRP
      isolates, 82% were also resistant to trimethoprim/sulfamethoxazole, 32% had
      additional resistance to tetracycline, and 26% to erythromycin. Antibiotic sales
      figures for all studied antibiotic subgroups decreased during the same period.
      Little correlation was found between antibiotic sales and PRP resistance rates,
      indicating that there are still other poorly defined factors contributing to the
      reported resistance levels in the population. However, although PRP strains in
      Sweden are becoming more commonly resistant to antibiotics other than beta
      lactams, the low and further reduced antibiotic sales still might have delayed
      the development and rapid spread of PRP in the population.

PMID- 16584304
TI  - Genotypic and phenotypic analysis of Clostridium difficile correlated with
      previous antibiotic exposure.
AB  - To analyze Clostridium difficile susceptibility results and genotypes in relation
      to antibiotic exposures that precipitated C. difficile-associated diarrhea
      (CDAD), we examined 83 nosocomial C. difficile isolates recovered at a tertiary
      care center in Boston, Massachusetts. MICs were determined by E-test methodology
      using modified Brucella agar. Isolates were genotyped by pulsed-field gel
      electrophoresis and restriction enzyme analysis. Antibiotic susceptibilities
      were: ciprofloxacin (0%), clindamycin (59%), trovafloxacin (63%), ceftriaxone
      (73%), piperacillin/tazobactam (100%), metronidazole (100%), and vancomycin
      (100%). The two most common strain groups, isolated from a total of 33 patients,
      were much more likely to be resistant to clindamycin, erythromycin, and
      trovafloxacin than other strain groups [79% (26 of 33) versus 2% (1 of 50),
      respectively]. Clindamycin exposure was strongly associated with CDAD caused by
      isolates that exhibited multiple resistance to clindamycin, erythromycin, and
      trovafloxacin (prevalence odds ratio, 4.2; 95% confidence interval, 1.1-16.8),
      whereas other antimicrobials did not yield significant associations. Resistance
      of specific C. difficile strains to clindamycin and other antimicrobial agents
      may contribute to their hospital dissemination and explain, in part, the
      propensity of clindamycin to trigger nosocomial outbreaks.

PMID- 16584305
TI  - Antimicrobial resistance and serotypes of nasopharyngeal strains of Streptococcus
      pneumoniae in Brazilian adolescents.
AB  - The aim of this study was to describe the frequency of antimicrobial-resistance
      and serotypes of nasopharyngeal pneumococcal isolates from adolescents. Clinical
      data and nasopharyngeal specimens for culture were collected from 1,013
      adolescents as a part of a population-based study. A total of 83 isolates of
      Streptococcus pneumoniae were identified (8.2%). Seventy-four of the 83 isolates
      were serotyped. The median age of the 83 adolescents colonized by pneumococci was
      14 years (mean 14 +/- 2.2 yrs); 55.4% were males. Intermediate resistance to
      penicillin was detected in 7.2% (6/83). No strain showed high resistance to
      penicillin. All isolates were susceptible to clindamycin, chloramphenicol,
      rifampin, and vancomycin; 37.3%, 18.1%, and 4.8% were resistant to trimethoprim
      sulfamethoxazole, tetracycline, and erythromycin, respectively. The most frequent
      serotypes (5-10% of strains each) were 6B, 6A, 23F, and 18C among 28
      serotypes/serogroups identified; 18.9% of the strains were nontypeable (NT).
      Intermediate resistance to penicillin was detected in serotypes 6B, 14, and NT.
      The rate of resistance to penicillin of nasopharyngeal isolates is low
      considering data from other studies about invasive strains recovered from
      children in Brazil. Serotype patterns are similar, except for type 14, which was
      unusually infrequent.

PMID- 16584306
TI  - Prevalence and clinical implications of Staphylococcus aureus with a vancomycin
      MIC of 4 microg/ml in Korea.
AB  - In addition to vancomycin-intermediate Staphylococcus aureus (VISA), S. aureus
      with a vancomycin MIC of 4 microg/ml has been reported to be the cause of
      therapeutic failure. This study was designed to determine the prevalence of
      methicillin-resistant S. aureus (MRSA) with a vancomycin MIC of 4 microg/ml and
      to clarify the clinical characteristics of infections caused by these isolates.
      During the 8-week period from April to May, 2001, 27 hospitals participated in a
      nationwide surveillance program for VISA and vancomycin-resistant S. aureus
      (VRSA) in Korea. After screening on brain-heart infusion agar containing 4
      microg/ml of vancomycin as previously described, 100 isolates with confluent
      growth were tested. The medical records of the patients involved were reviewed.
      Even though VISA or VRSA was not detected among 3,756 MRSA isolates, 18 (0.5%)
      had a vancomycin MIC of 4 microg/ml. The infections in 12 of these patients,
      excluding 5 that were colonized, were 8 chronic osteomyelitis, 1 surgical site
      infection, 1 pneumonia, 1 intra-abdominal infection, and 1 catheter-related
      infection. Although 11 cases were exposed to glycopeptides for a long time
      (median 56 days), the site of infection became culture-negative in only 1 case.
      Two patients died of their S. aureus infections. MRSA with a vancomycin MIC of 4
      microg/ml was rare. Chronic osteomyelitis was the most common type of infection,
      and prolonged exposure to glycopeptides was associated with reduced
      susceptibility to vancomycin.

PMID- 16584307
TI  - Evaluation of imipenem/imipenem+EDTA disk method for detection of metallo-beta
      lactamase-producing Klebsiella pneumoniae isolated from blood cultures.
AB  - The objective of this study was to evaluate the imipenem (IMP) and IMP+EDTA
      (IMP/IMP+EDTA) disk method for the detection of metallo-beta-lactamases (MBLs) in
      clinical isolates of Klebsiella pneumoniae with various MIC levels to IMP. Forty
      one blood isolates of K. pneumoniae with MIC to IMP ranging from < or =0.5 to >
      or =16 microg/ml were examined. The MICs were determined by VITEK-2 (bioMerieux
      Vitek two, France). Disks of 10 microg IMP with and without the addition of 0.5 M
      EDTA were used for the IMP/IMP+EDTA disk method. The E-test (AB Biodisk, Solna,
      Sweden) for MBL detection was also used. All isolates were examined for the bla
      (VIM-1) gene by PCR and for clonality of VIM-1-producing isolates by pulsed-field
      gel electrophoresis (PFGE). All isolates with MIC values of IMP < or =0.5
      microg/ml exhibited no differences in inhibition zone diameters (IZD) produced by
      IMP and IMP+EDTA disks, whereas the isolates with MICs > or =1 microg/ml showed
      an increase in IZD, ranging from 8 to 26 mm. All isolates with MIC values of > or
      =1 microg/ml were found positive for the bla (VIM-1) gene by PCR and for MBL
      production by the E-test, whereas none of isolates with MICs <0.5 microg/ml was
      found positive by any of the tests. DNA restriction fragments generated by PFGE
      of VIM-1-producing isolates were classified in four main types. The IMP/IMP+EDTA
      disk method is simple to perform, sensitive, and specific for detection of MBL
      producing K. pneumoniae clinical isolates. K. pneumoniae isolates with MICs of
      IMP > or =1 microg/ml and/or IZD produced by IMP disk <19 mm should be tested for
      MBL production.

PMID- 16584308
TI  - Prevalence of plasmid-mediated AmpC beta-lactamases in Escherichia coli and
      Klebsiella pneumoniae in Korea.
AB  - Cefoxitin-resistant Escherichia coli and Klebsiella pneumoniae are relatively
      prevalent in Korea, suggesting dissemination of plasmid-mediated AmpC beta
      lactamases. In this study, 238 isolates of cefoxitin-resistant E. coli and K.
      pneumoniae (not including subspecies ozaenae and rhinoscleromatis) were collected
      in 2003 from 16 Korean hospitals. The prevalence of plasmid-mediated AmpC beta
      lactamases was determined by PCR. The AmpC gene alleles detected in E. coli and
      K. pneumoniae were bla(DHA-1), 10 (8.6%) and 93 (76.2%); bla(CMY-1)-like, 14
      (12.1%) and 2 (1.6%); and bla(CMY-2)-like, 38 (32.7%) and 1 (0.8%) isolates,
      respectively. The genes identified were bla(DHA-1), bla(CMY10)-like, and bla(CMY
      2)-like, and a new variant, bla(CMY-18). Plasmidmediated AmpC gene allele
      positive isolates were present both in large city and in small province
      hospitals, as well as in isolates from outpatients. The proportions of plasmid
      mediated AmpC gene-positive isolates were similar in both expanded spectrum beta
      lactamase (ESBL)-producing and -nonproducing isolates. In conclusion, DHA-1, CMY
      2-like, and CMY-10-like plasmid-mediated AmpC beta-lactamase-producing K.
      pneumoniae and E. coli isolates are widely disseminated in both large city and
      small province hospitals. Absence of bla(CMY-1) and detection of a novel variant
      of bla(CMY-2), bla(CMY-18), indicate continued evolution of the prototype genes.
      Similar proportions of plasmid-mediated AmpC gene-positive isolates in both ESBL
      producing and -nonproducing isolates suggest unhindered future spread of these
      resistances.

PMID- 16584309
TI  - Endemic extended-spectrum beta-lactamase-producing Klebsiella pneumoniae at an
      intensive care unit: risk factors for colonization and infection.
AB  - A prospective cohort study was undertaken to describe the epidemiology of
      extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBLKp)
      acquisition at an intensive care unit (ICU) in a non-outbreak setting.
      Surveillance for ESBLKp colonization and infection was performed in patients
      admitted at the ICU from January, 2000, to May, 2001. Screening for ESBLKp
      intestinal colonization was done by culturing rectal swab specimens at admission,
      72 hr after admission and weekly until discharge or detection of ESBLKp. The
      incidence of ESBLKp intestinal colonization was 5.8/1,000 patient-days (95%CI,
      3.4-10.1), and of ESBLKp infection was 1.7/1,000 patient-days (95%CI, 0.7-4.2).
      Use of vancomycin (OR 6.6; 95%CI, 1.73-25.28), amphotericin B (OR 12.0; 95%CI,
      1.79-80.51), metronidazole (OR 5.3; 95%CI, 1.10-25.65), and ciprofloxacin (OR
      0.1; 95%CI, 0.01-0.97) were independently associated with ESBLKp intestinal
      colonization. Previous ESBLKp colonization (OR 60.6; 95%CI, 56.33-578.73) was
      independently associated with ESBLKp infection. Each ICU-acquired ESBLKp isolate
      belonged to a different genotype by ERIC-PCR or pulsed-field gel electrophoresis
      (PFGE) and had a different plasmid profile, suggesting that cross transmission
      was not the main source for ESBLKp acquisition. Factors associated with ESBLKp in
      the non-outbreak setting were different from those previously reported during
      outbreaks. Intestinal ESBLKp colonization was confirmed as a risk factor for
      infection by this pathogen.

PMID- 16584310
TI  - A case of ventricular drainage infection with a rare pathogen in cerebrospinal
      fluid: vancomycin-resistant Enterococcus faecium.
AB  - The purpose of this study was to describe a patient, 7-month-old child with
      ventriculoperitoneal shunts for hydrocephalus with ventriculitis caused by
      vancomycin-resistant Enterococcus faecium. Two ventriculoperitoneal shunts were
      inserted just after birth and on the second month. On the sixth month, both
      shunts were removed because of dysfunction, and external drainage was inserted.
      The child developed fever, and lumbar puncture revealed a high leukocyte count
      and protein concentration after external drainage. Cerebrospinal fluid (CSF)
      cultures yielded E. faecium, which was resistant to ampicillin, erythromycin,
      gentamicin, penicillin G, vancomycin, and teicoplanin and was susceptible to
      chloramphenicol, ciprofloxacin, streptomycin, levofloxacin, and rifampin, as
      determined by the disk diffusion method. As a result of the antimicrobial
      susceptibility tests, multidrug antibiotic therapy was changed from vancomycin
      and ceftazidime to chloramphenicol, rifampin, and meropenem. In addition, a
      rifampin-clindamycin-impregnated shunt (The Codman Hakim Bactiseal, Raynham, MA)
      was inserted. The patient became afebrile, and CSF cultures were sterile after 15
      days of yielding E. faecium. Implantation of the rifampin-clindamycin-impregnated
      shunt and timely use of appropriate antibiotics for 10 days according to
      antimicrobial susceptibility testing seem to be important in the resolution of
      vancomycin-resistant enterococci infections, especially in countries where
      linezolid and quinupristin-dalfopristin are not in use yet.

PMID- 16584311
TI  - Vancomycin-resistant Enterococci may obtain nutritional support by scavenging
      carbohydrate fragments generated during mucin degradation by the anaerobic
      microbiota of the colon.
AB  - Vancomycin-resistant Enterococcus (VRE) is an important nosocomial pathogen that
      colonizes the intestinal tract. The substrates that provide nutritional support
      for VRE in the colon are not known. We tested the hypothesis that enzymatic
      breakdown of complex polysaccharides and glycoconjugates by other members of the
      indigenous microbiota could provide a source of nutrients for VRE. Nine
      vancomycin-resistant E. faecium strains were unable to ferment complex plant
      polysaccharides or hog gastric or bovine submaxillary mucin; however, each of the
      strains was able to ferment monosaccharides that are components of mucins and
      plant polysaccharides. Preincubation of hog gastric mucin with partially purified
      enzyme mixtures obtained from supernatants of Ruminococcus torques or a human
      stool specimen resulted in release of monosaccharides that supported growth of
      VRE. These results suggest that enzymatic breakdown of complex polysaccharides
      such as mucin by members of the indigenous microbiota may provide a source of
      nutritional support for VRE.

PMID- 16584312
TI  - Molecular analysis of Salmonella enteritidis and Typhimurium clinical and food
      isolates by pulsed-field gel electrophoresis in Bogota, Colombia.
AB  - In 1997, the Microbiology Group of the Colombian Instituto Nacional de Salud set
      up a surveillance program with the National Public Health Laboratories to monitor
      the principal etiological agents responsible for acute diarrheal disease. The
      main goal of this study was to determine the XbaI DNA digestion patterns of
      clinical and food Salmonella spp. isolates recovered in Bogota from 1997 to 2002,
      and related them to the susceptibility patterns to antimicrobial agents. Two
      hundred and twenty-four Salmonella spp. isolates were studied, 153 (63%) S.
      Enteritidis and 71 (37%) S. Typhimurium. Pulsed-field gel electrophoresis (PFGE)
      was done using the XbaI restriction enzyme and Salmonella Braenderup H9812 as the
      molecular weight marker. For S. Enteritidis, pattern S. En0001 was found to be
      prevalent in 127 (83%) isolates, 78 (61%) susceptible to the antimicrobial agents
      tested. For S. Typhimurium, pattern S. Typ0001 was predominant in 18 (25%)
      isolates with different antimicrobial resistance profiles. Patterns S. En0001 and
      S. Typ0001 prevailed monthly during the 6 years of the study. Data collected
      demonstrate that there was a dominant pattern of S. Enteritidis and S.
      Typhimurium circulating in clinical and food isolates in Bogota, Colombia.

PMID- 16584313
TI  - Variability in antimicrobial resistance among Salmonella enterica strains from
      fattening pigs and sows.
AB  - The aim of this study was to determine the prevalence of antibiotic resistance
      and different resistance patterns for Salmonella isolates collected from Belgian
      sows and fattening pigs at different ages and at slaughter. The most frequently
      isolated serotypes were S. Typhimurium (42.3%), S. Derby (25.1%), S. Goldcoast
      (7.3%), and S. Infantis (4.8%). All 901 isolates were submitted to antimicrobial
      susceptibility testing for 14 compounds using the disc agar diffusion test. The
      highest percentage of resistance was found to oxytetracycline (34.2%),
      streptomycin (32.5%), sulfamethizole (27.6%), and ampicillin (24.9%). Three of
      the isolates showed resistance to cephalosporins and none to second-generation
      fluoroquinolones. Multiresistance (resistance to > or =2 antimicrobials) was
      observed in 33.2% of the strains. Differences in resistance patterns were
      observed between and within serotypes as well as genotypes. A significant lower
      proportion (p < 0.01) of resistant strains was recovered in fecal samples from
      sows (23/56) than from fattening pigs during the weaning (30/30), growing
      (79/85), and finishing periods (45/52). The proportion of resistant strains
      recovered from fecal samples taken at the herd (154/167) was higher than in the
      samples collected at the slaughterhouse (75/140). When designing antimicrobial
      resistance surveillance programs for Salmonella in pigs, it is important to take
      multiple samples within each herd from both sows and fattening pigs at different
      time points.

PMID- 16584314
TI  - An integrated study of acute effects of valproic acid in the liver using
      metabonomics, proteomics, and transcriptomics platforms.
AB  - An integrated omics approach was undertaken in order to elucidate a systems
      biology level understanding of the acute hepatotoxcity of valproic acid (VPA).
      Metabonomics, proteomics and gene expression microarray platforms were employed
      in this systems biology study. CD-1 female pregnant mice were injected
      subcutaneously with 600 mg/kg VPA or vehicle control. Urine, serum, and liver
      tissue were collected at 6, 12, and 24 h after dosing. Principal component
      analysis (PCA) of the metabonomics data showed clustering of the dosed groups
      away from the controls for the urine samples. Looser clustering was seen in the
      other sample sets investigated. However, VPA administration resulted in altered
      glucose concentrations in urine samples at 12 and 24 h and in aqueous liver
      tissue extracts at 12 h after VPA administration. Proteomics studies identified
      two proteins, glycogen phosphorylase and amylo-1,6-glucosidase, which were
      increased in dosed animals relative to control. Both of these proteins are
      involved in converting glycogen to glucose. Examination of the expression of
      20,000 liver genes did not reveal significantly altered expression at 6, 12, or
      24 h after VPA exposure. The combined studies indicated a perturbation in the
      glycogenolysis pathway following administration of VPA.

PMID- 16584315
TI  - Meta-analysis of published transcriptional and translational fold changes reveals
      a preference for low-fold inductions.
AB  - The goals of this study were to gain a better quantitative understanding of the
      dynamic range of transcriptional and translational response observed in
      biological systems and to examine the reporting of regulatory events for trends
      and biases. A straightforward pattern-matching routine extracted 3,408
      independent observations regarding transcriptional fold-changes and 1,125
      regarding translational fold-changes from over 15 million MEDLINE abstracts.
      Approximately 95% of reported changes were > or =2-fold. Further, the historical
      trend of reporting individual fold-changes is declining in favor of high
      throughput methods for transcription but not translation. Where it was possible
      to compare the average fold-changes in transcription and translation for the same
      gene/product (203 examples), approximately 53% were a < or =2-fold difference,
      suggesting a loose tendency for the two to be coupled in magnitude. We found also
      that approximately three-fourths of reported regulatory events have been at the
      transcriptional level. The frequency distribution appears to be normally
      distributed and peaks near 2-fold, suggesting that nature selects for a low
      energy solution to regulatory responses. Because high-throughput technologies
      ordinarily sacrifice measurement quality for quantity, this also suggests that
      many regulatory events may not be reliably detectable by such technologies. Text
      mining of regulatory events and responses provides additional information
      incorporable into microarray analysis, such as prior fold-change observations and
      flagging genes that are regulated post-transcription. All extracted regulation
      and response patterns can be downloaded at the following website:
      www.ou.edu/microarray/ oumcf/Meta_analysis.xls.

PMID- 16584316
TI  - Combining gene annotations and gene expression data in model-based clustering:
      weighted method.
AB  - It has been increasingly recognized that incorporating prior knowledge into
      cluster analysis can result in more reliable and meaningful clusters. In contrast
      to the standard modelbased clustering with a global mixture model, which does not
      use any prior information, a stratified mixture model was recently proposed to
      incorporate gene functions or biological pathways as priors in model-based
      clustering of gene expression profiles: various gene functional groups form the
      strata in a stratified mixture model. Albeit useful, the stratified method may be
      less efficient than the global analysis if the strata are non-informative to
      clustering. We propose a weighted method that aims to strike a balance between a
      stratified analysis and a global analysis: it weights between the clustering
      results of the stratified analysis and that of the global analysis; the weight is
      determined by data. More generally, the weighted method can take advantage of the
      hierarchical structure of most existing gene functional annotation systems, such
      as MIPS and Gene Ontology (GO), and facilitate choosing appropriate gene
      functional groups as priors. We use simulated data and real data to demonstrate
      the feasibility and advantages of the proposed method.

PMID- 16584317
TI  - Diffusion kernel-based logistic regression models for protein function
      prediction.
AB  - Assigning functions to unknown proteins is one of the most important problems in
      proteomics. Several approaches have used protein-protein interaction data to
      predict protein functions. We previously developed a Markov random field (MRF)
      based method to infer a protein's functions using protein-protein interaction
      data and the functional annotations of its protein interaction partners. In the
      original model, only direct interactions were considered and each function was
      considered separately. In this study, we develop a new model which extends direct
      interactions to all neighboring proteins, and one function to multiple functions.
      The goal is to understand a protein's function based on information on all the
      neighboring proteins in the interaction network. We first developed a novel
      kernel logistic regression (KLR) method based on diffusion kernels for protein
      interaction networks. The diffusion kernels provide means to incorporate all
      neighbors of proteins in the network. Second, we identified a set of functions
      that are highly correlated with the function of interest, referred to as the
      correlated functions, using the chi-square test. Third, the correlated functions
      were incorporated into our new KLR model. Fourth, we extended our model by
      incorporating multiple biological data sources such as protein domains, protein
      complexes, and gene expressions by converting them into networks. We showed that
      the KLR approach of incorporating all protein neighbors significantly improved
      the accuracy of protein function predictions over the MRF model. The
      incorporation of multiple data sets also improved prediction accuracy. The
      prediction accuracy is comparable to another protein function classifier based on
      the support vector machine (SVM), using a diffusion kernel. The advantages of the
      KLR model include its simplicity as well as its ability to explore the
      contribution of neighbors to the functions of proteins of interest.

PMID- 16584318
TI  - Prediction of protein functional specificity without an alignment.
AB  - We propose a new approach to predict functional specificity of proteins from
      their amino acid sequences. Our approach is based on two things: structural
      Multilevel Neighborhoods of Atom (MNA) descriptors and an original Bayesian
      algorithm. Usually, a protein sequence is presented as a string of amino acid
      symbols. Here we introduce a new description of an amino acid sequence: a set of
      structural MNA descriptors. The MNA descriptor is a string describing an atom and
      its neighbor atoms according to the selected level. In this work, we also use
      description of a protein sequence as a set of peptides (strings of amino acid
      symbols). We performed a case study on two subsubclasses of enzyme nomenclature
      (EC). It is shown that B-statistics give a sufficient predictive power of enzyme
      specificity prediction for both MNA descriptors and peptides. We also showed that
      MNA descriptors give higher accuracy values in comparison with peptides and also
      provide a choice of MNA descriptor levels for best accuracy prediction. The
      highest average accuracy prediction that was achieved was 0.98.

PMID- 16584319
TI  - Genetic variation and the mitogen-activated protein kinase (MAPK) signaling
      pathway.
AB  - Non-synonymous single nucleotide polymorphisms (nsSNPs) are known to alter
      protein function, contributing to disease susceptibility. This report explores
      the nature of nsSNPs in the gene products of the highly conserved mitogen
      activated protein kinase (MAPK) signaling pathways already implicated in cancer
      development. MAPK signaling pathways regulate cellular processes such as
      proliferation, differentiation, apoptosis, and survival mediated through
      interconnected signaling cascades. Using the dbSNP database, we have identified
      25 nsSNPs in 17 out of 98 MAPK genes studied. Computational algorithms were used
      to predict whether the amino acid substitutions were evolutionarily tolerated, or
      affected putative functional units such as phosphorylation sites, protein motifs
      and domains. This study predicts that 36% of nsSNPs are likely to have functional
      consequences, based on evolutionary conservation analysis, and 36% based on
      phosphorylation prediction analysis. All such nsSNPs represent potentially
      functional and disease-causing/modifying alleles. More interestingly, the
      epistatic relationships discussed in this report represent potential synergistic/
      antagonistic/additive effects of nsSNP combinations found within the same
      protein, or within members of the same protein complex and cascades. This
      strategy can effectively determine which nsSNPs potentially alter protein
      function, and can be utilized to study the genetic architecture and disease
      association of other biological protein complexes and networks.

PMID- 16584321
TI  - Prediction of equine risk of West Nile virus infection based on dead bird
      surveillance.
AB  - Since the introduction of West Nile Virus (WNV) to the United States in 1999, the
      efficacy of dead bird surveillance for the prediction of human and veterinary WNV
      infection has been an issue of debate. We utilized South Carolina's Department of
      Health and Environmental Control surveillance data from 2003 to determine whether
      dead bird surveillance accurately predicts equine WNV infection on a county
      level. We adjusted for human population density as a potential confounder of an
      association between WNV-positive dead bird counts and mammalian WNV risk. We
      found a strong positive association between avian risk of WNV death and
      subsequent equine mortality due to WNV in South Carolina even after adjusting for
      human population density. Sensitivity of dead bird surveillance as a predictor of
      future equine WNV risk was far superior to mosquito surveillance (95% vs. 9.5%,
      respectively). A Poisson regression model of the equine WNV rate as a function of
      WNV-positive dead bird rate, adjusting for population density and taking into
      account effect modification by population density shows a good fit with the data.
      Unlike most previous studies, we control for potential confounding of the dead,
      WNVpositive bird-equine WNV infection association by human population density.
      Yet, the positive association between dead bird surveillance and equine WNV risk
      remains strong and statistically significant, indicating that dead bird
      surveillance remains a valuable tool of WNV surveillance.

PMID- 16584322
TI  - Detection of Babesia and Anaplasma species in rabbits from Texas and Georgia,
      USA.
AB  - Rabbits have been shown to harbor a suite of zoonotic organisms, including a
      Babesia species, Borrelia burgdorferi, and Anaplasma phagocytophilum. In this
      study, we conducted a molecular survey for various tick-borne pathogens in three
      species of rabbits from Texas and Georgia. Of 18 black-tailed jackrabbits (Lepus
      californicus) tested from Texas, six (28%) were polymerase chain reaction (PCR)
      positive for Babesia, and nucleotide sequencing revealed two distinct species or
      strains. Two jackrabbits were infected with a Babesia species or strain (Babesia
      sp. A) that was nearly identical (99.9%) to a piroplasm previously detected in
      humans from Washington state, and the remaining four jackrabbits were infected
      with a Babesia species (Babesia sp. B) that was most similar (99.7%) to a Babesia
      species detected in cottontail rabbits from Massachusetts and humans from
      Kentucky and Missouri. Eleven (61%) black-tailed jackrabbits were positive for A.
      bovis, and one was positive for A. phagocytophilum. Two of four desert
      cottontails (Sylvilagus audubonii) from Texas were positive for the Babesia sp.
      B, and one desert cottontail each was positive for A. bovis and A.
      phagocytophilum. One of these desert cottontails was coinfected with the Babesia
      sp. B and A. phagocytophilum, and five jackrabbits were coinfected with Babesia
      species and A. bovis. Of 19 eastern cottontails (S. floridanus) from Georgia,
      only one (5.3%) was positive for A. phagocytophilum, and three (15.8%) were
      positive for A. bovis. No rabbits from Texas or Georgia were positive for
      Borrelia species. The only tick species detected on the Texas and Georgia rabbits
      was the rabbit tick, Haemaphysalis leporispalustris. These data extend the
      geographic and host range of these pathogens, and because both the Babesia
      species and A. phagocytophilum are potential zoonotic pathogens, it is important
      to be aware that these organisms are enzootic in parts of the southern United
      States.

PMID- 16584323
TI  - Purdue University-Banfield National Companion Animal Surveillance Program for
      emerging and zoonotic diseases.
AB  - A National Companion Animal Surveillance Program (NCASP) was established at
      Purdue University to monitor clinical syndromes and diseases using the electronic
      medical records of >80,000 companion animals visiting >500 Banfield hospitals
      weekly in 44 states. With funding from the Centers for Disease Control and
      Prevention, NCASP was initially developed for syndromic surveillance of Category
      A agents of bioterrorism. Surveillance was expanded through inclusion of
      electronic reports from Antech Diagnostics, a nationwide network of integrated
      veterinary diagnostic laboratories serving >18,000 private veterinary practices.
      NCASP characterizes and displays temporal and spatial patterns of diseases in
      dogs, cats, and other companion animals. It detects unusual clusters of potential
      emerging/zoonotic infections and monitors flea and tick activity. Data is
      processed and analyzed using SAS and ESRI software products. The NCASP can be
      used by veterinarians to enhance their practice of evidence-based medicine by
      providing information needed to individualize vaccine protocols for animals in
      specific geographic areas.

PMID- 16584324
TI  - A study of the presence of B. burgdorferi, Anaplasma (previously Ehrlichia)
      phagocytophilum, Rickettsia, and Babesia in Ixodes ricinus collected within the
      territory of Belluno, Italy.
AB  - In the years 2000 and 2001, we sampled ticks in order to establish the
      distribution of Ixodes ricinus in the province of Belluno; 5987 tick samples from
      244 sites throughout the province were gathered, by dragging for a 5-min period.
      In 40 sites, seasonal variations and cycle stages of the parasites were studied
      at monthly intervals from March to September. A polymerase chain reaction (PCR)
      technique was used to identify the tick-infected sites. Of 1931 individual ticks,
      8.23% were positive for Borrelia burgdorferi, 4.4% were positive for Ehrlichia,
      1.6% were positive for Rickettsia, and 1.6% were positive for Babesia. The co
      presence of Borrelia and Ehrlichia (1.2%) and Babesia (0.5%), Borrelia, Ehrlichia
      and Rickettsia (0.1%) was also found.

PMID- 16584325
TI  - Natural tick-borne encephalitis virus infection among wild small mammals in the
      southeastern part of western Siberia, Russia.
AB  - Infestation of small mammals, including common shrews Sorex araneus L., field
      mice Apodemus agrarius Pallas, and red voles Clethrionomus rutilus Schreber, with
      immature Ixodes persulcatus ticks and their infection with tickborne encephalitis
      virus (TBEV) were studied in the forest-steppe habitat in the vicinity of
      Novosibirsk, Russia. Larval ticks parasitize all three host species, but
      virtually all nymphs were found only on field mice and red voles. Detection of
      the viral RNA using reverse transcription (RT) with subsequent nested polymerase
      chain reaction (nPCR) and of viral antigen using enzyme-linked immunosorbent
      assay (ELISA) revealed a high prevalence of TBEV-positive animals in both the
      summer and winter. The proportion of small mammals with hemagglutination
      inhibition (HI) antibodies was significantly lower than with ELISA-detected
      antibodies. Taken together, the data suggest that small mammals may maintain TBEV
      as a persistent infection throughout the year.

PMID- 16584326
TI  - West Nile virus among hospitalized, febrile patients: a case for expanding
      diagnostic testing.
AB  - In Georgia, most individuals reported with West Nile virus (WNV) disease have
      been diagnosed with West Nile neuroinvasive disease (WNND). Relatively few cases
      of West Nile Fever (WNF) are reported, and the burden of illness due to WNV is
      likely underestimated. From July through October 2003, WNV serologic testing was
      performed on enrolled patients>or=18 years of age with fever admitted to a large,
      urban hospital in Atlanta, Georgia through the emergency department (ED).
      Patients' history, clinical, and laboratory data were recorded. Residual blood
      drawn in the ED was tested to determine the presence of WNV IgG and IgM
      antibodies. Of 254 patients tested for WNV, four (1.6%) patients were positive
      for WNV IgM and IgG antibodies, and had a clinical illness compatible with WNV.
      None of the four positive patients were clinically suspected of having WNV
      infection; discharge diagnoses included pneumonia, migraine, stroke, and gout.
      These four patients accounted for 80% of all WNV diagnosed in this hospital, 44%
      of all cases in Fulton County, and 7% of all cases reported in Georgia in 2003.
      The occurrence of WNV disease may be substantially greater than currently
      reflected in disease statistics in Georgia and many other states. When indicators
      of WNV activity are present and patients are likely to have had intensive
      mosquito exposure, WNV should be considered in the differential diagnosis of
      seriously ill, febrile patients.

PMID- 16584327
TI  - Susceptibility of different triatomine species to Trypanosoma rangeli
      experimental infection.
AB  - Trypanosoma rangeli is a kinetoplastid protozoan parasite that has been found in
      the majority of Latin American countries, overlapping its distribution area with
      that of Trypanosoma cruzi, the causative agent of Chagas disease. This parasite
      shares the same reservoirs and vectors as T. cruzi. Triatomines from genus
      Rhodnius are considered the most susceptible hosts to infection. In this work, we
      report the susceptibility of different triatomine species (Rhodnius neglectus,
      Panstrongylus megistus, Triatoma infestans, T. sordida, T. braziliensis, and T.
      vitticeps) to experimental infection by T. rangeli isolated from Didelphis
      albiventris in a highly endemic region for Chagas disease. An intense parasitism
      was evidenced in feces (56% to 81%) of the majority of the species studied on the
      10th day after infection, decreasing during the period of the experiment (30
      days). T. vitticeps did not present parasites in feces at any time. All
      triatomine species presented parasites in the hemolymph. In T. vitticeps and P.
      megistus, this parasitism was scarce (6.3% and 6.6%, respectively). In the other
      species, the parasitism was variable (62.5% to 100%). Triatomine mortality varied
      between 3% to 40%, increasing during the infection in all species studied. The
      lowest mortality was observed for T. infestans. Also, we showed that only
      trypomastigotes forms from salivary glands, and hemolymph were infective for
      mice. We conclude that all triatomine species used were susceptible to infection
      by T. rangeli at different levels. There was no direct correlation between
      intensity of parasitism and mortality.

PMID- 16584328
TI  - West Nile virus antibodies in avian species of Georgia, USA: 2000-2004.
AB  - West Nile virus (WNV) was first isolated in the state of Georgia in the summer of
      2001. As amplifying hosts of WNV, avian species play an important role in the
      distribution and epidemiology of the virus. The objective of this study was to
      identify avian species that are locally involved as potential amplifying hosts of
      WNV and can serve as indicators of WNV transmission over the physiographic and
      land use variation present in the southeastern United States. Avian serum samples
      (n=14,077) from 83 species of birds captured throughout Georgia during the
      summers of 2000-2004 were tested by a plaque reduction neutralization test for
      antibodies to WNV and St. Louis encephalitis virus. Over the 5-year period, WNV
      neutralizing antibodies were detected in 869 (6.2%) samples. The WNV
      seroprevalence increased significantly throughout the study and was species
      dependent. The highest antibody prevalence rates were detected in rock pigeons
      (Columba livia), northern cardinals (Cardinalis cardinalis), common ground doves
      (Columbina passerina), grey catbirds (Deumetella carolinensis), and northern
      mockingbirds (Mimus polyglottos). Northern cardinals, in addition to having high
      geometric mean antibody titers and seroprevalence rates, were commonly found in
      all land use types and physiographic regions. Rock pigeons, common ground doves,
      grey catbirds, and northern mockingbirds, although also having high
      seroprevalence rates and high antibody titers against WNV, were more restricted
      in their distribution and therefore may be of more utility when attempting to
      assess exposure rates in specific habitat types. Of all species tested, northern
      cardinals represent the best potential avian indicator species for widespread
      serologic-based studies of WNV throughout Georgia due to their extensive range,
      ease of capture, and high antibody rates and titers. Due to the large geographic
      area covered by this species, their utility as a WNV sentinel species may include
      most of the eastern United States.

PMID- 16584329
TI  - Factors affecting the geographic distribution of West Nile virus in Georgia, USA:
      2002-2004.
AB  - The distribution of West Nile virus (WNV) is dependent on the occurrence of both
      susceptible avian reservoir hosts and competent mosquito vectors. Both factors
      can be influenced by geographic variables such as land use/landcover, elevation,
      human population density, physiographic region, and temperature. The current
      study uses geographic information systems (GIS) and logistic regression analyses
      to model the distribution of WNV in the state of Georgia based on a wild bird
      indicator system, and to identify human and environmental predictor variables
      that are important in the determination of WNV distribution. A database for
      Georgia was constructed that included (1) location points of all the avian
      samples tested for WNV, (2) local land use classifications, including
      temperature, physiographic divisions, land use/landcover, and elevation, (3)
      human demographic data from the U.S. Census, and (4) statistics summarizing land
      cover, elevation, and climate within a 1-km-radius landscape around each sample
      point. Logistic regression analysis was carried out using the serostatus of avian
      collection sites as the dependent variable. Temperature, housing density,
      urban/suburban land use, and mountain physiographic region were important
      variables in predicting the distribution of WNV in the state of Georgia. While
      weak, the positive correlation between WNV-antibody positive sites and the
      urban/suburban environment was consistent throughout the study period. The risks
      associated with WNV endemicity appear to be increased in urban/ suburban areas
      and decreased in the mountainous region of the state. This information may be
      used in addressing regional public health needs and mosquito control programs.

PMID- 16584330
TI  - Use of real-time quantitative PCR targeting the msp2 protein gene to identify
      cryptic Anaplasma phagocytophilum infections in wildlife and domestic animals.
AB  - Anaplasma phagocytophilum is an emerging pathogen throughout much of the
      Holarctic, where Ixodes spp. tick vectors occur. This organism was expected to be
      present at study sites in Humboldt County, north-western California, based on the
      presence of appropriate tick vectors, seropositivity in sentinel hosts, and
      previously reported human infections. However, despite high seroprevalence
      suggesting circulating A. phagocytophilum, active infections in dogs and wildlife
      (including suspected reservoir species) were rare using published polymerase
      chain reaction (PCR) protocols. This finding was possible if the published PCR
      protocol lacked sensitivity for strains in the study areas. We report a new
      TaqMan-PCR (TM-PCR) assay targeting the msp2 gene that has greater sensitivity
      and specificity for diverse A. phagocytophilum strains from this region. The new
      assay detected as few as one plasmid copy and a range of genetically diverse
      strains of A. phagocytophilum. Specificity was confirmed by failure to amplify
      targets of closely related bacteria. Application of the TM-PCR to samples from
      northern California confirmed PCR-positivity in 94 woodrats (71%; n=134), three
      (4%; n=80) bears, and seven (7%; n=97) domestic dogs. The msp2 TM-PCR protocol
      appears to be more sensitive for use in assays of samples from parts of western
      North America and possibly in other regions where populations are genetically
      diverse or divergent from eastern United States strains of A. phagocytophilum.

PMID- 16584331
TI  - Spatio-temporal analyses of West Nile virus transmission in Culex mosquitoes in
      northern Illinois, USA, 2004.
AB  - After a severe outbreak of West Nile virus (WNV) in Cook County, Illinois, in
      2002, detections of WNV in mosquitoes were frequent across the state in the
      following years despite small numbers of human cases. We conducted a spatio
      temporal analysis of Culex (subgenus Culex) mosquitoes collected in 2004 in three
      mosquito abatement districts (MAD) in Cook County by calculating monthly
      estimates of mosquito density, prevalence of infected mosquitoes, and exposure
      intensity, which in turn is a product of mosquito density and infection rates.
      Mosquito infections were detected early at three sites in late May and were
      widely detected throughout the three MADs in the summer with infection rates as
      high as 13 per 1000 in August. Exposure intensities were higher at sites adjacent
      to the Des Plaines River, especially in August and September. The aggregated
      pattern of WNV transmission along the river might be related to the existence of
      substantial forest preserves and wetlands that might produce ecological
      conditions favorable for mosquito proliferation and interactions between
      mosquitoes and birds.

PMID- 16584332
TI  - Co-detection of Bartonella henselae, Borrelia burgdorferi, and Anaplasma
      phagocytophilum in Ixodes pacificus ticks from California, USA.
AB  - Presence of Bartonella DNA was explored in 168 questing adult Ixodes pacificus
      ticks from Santa Cruz County, California. Bartonella henselae type I DNA was
      amplified from 11 ticks (6.55%); previously, two (1.19%) were found to be
      infected with Borrelia burgdorferi and five (2.98%) with Anaplasma
      phagocytophilum. Detection of B. henselae was not dependent on co-infection. The
      present study offers additional evidence that Ixodes spp. ticks may act as hosts
      and possibly vectors for B. henselae.

PMID- 16584333
TI  - A reverse transcriptase-polymerase chain reaction assay of Borrelia burgdorferi
      16S rRNA for highly sensitive quantification of pathogen load in a vector.
AB  - We developed a real-time quantitative detection assay for the pathogen Borrelia
      burgdorferi, a Lyme borreliosis (LB) agent, using reverse transcription
      polymerase chain reaction (RT-PCR) with primers and probe for a Borrelia genus
      specific region of 16S ribosomal RNA. The standard curve of the assay was linear
      by semi-log plot over more than five orders of magnitude, and the detection limit
      of the assay was one thousandth of a single cell of B. burgdorferi. The minimum
      target level for detection using the RT-PCR assay for 16S RNA was 40-fold lower
      than the RT-PCR assay for messenger RNA of ospA, a highly expressed, plasmid
      borne gene, and 1600-fold lower than the RT-PCR assay for messenger RNA of p66, a
      chromosome-borne gene of B. burgdorferi. The 16S rRNA assay was then applied in
      an experimental setting for monitoring the spirochetal load in B. burgdorferi
      infected Ixodes scapularis ticks before and after they fed on Peromyscus leucopus
      mice immunized with recombinant OspA. Unfed infected ticks had a mean of 2,240
      spirochetes per tick, and after feeding on non-immunized mice and engorgement,
      the mean number of spirochetes increased to 223,900 per tick. In contrast, there
      were either no or <or=7 spirochetes in ticks that had fed on OspA-immunized mice.

PMID- 16584335
TI  - Lasers in periodontics: a review of the literature.
AB  - BACKGROUND: Despite the large number of publications, there is still controversy
      among clinicians regarding the application of dental lasers to the treatment of
      chronic periodontitis. The purpose of this review is to analyze the peer-reviewed
      research literature to determine the state of the science concerning the
      application of lasers to common oral soft tissue problems, root surface
      detoxification, and the treatment of chronic periodontitis. METHODS: A
      comprehensive computer-based search combined the following databases into one
      search: Medline, Current Contents, and the Cumulated Index of Nursing and Allied
      Health. This search also used key words. In addition, hand searches were done for
      several journals not cataloged in the databases, and the reference lists from
      published articles were checked. All articles were considered individually to
      eliminate non-peer-reviewed articles, those dealing with commercial laser
      technology, and those considered by the author to be purely opinion articles,
      leaving 278 possible articles. RESULTS: There is a considerable conflict in
      results for both laboratory studies and clinical trials, even when using the same
      laser wavelength. A meaningful comparison between various clinical studies or
      between laser and conventional therapy is difficult at best and likely impossible
      at the present. Reasons for this dilemma are several, such as different laser
      wavelengths; wide variations in laser parameters; insufficient reporting of
      parameters that, in turn, does not allow calculation of energy density;
      differences in experimental design, lack of proper controls, and differences in
      severity of disease and treatment protocols; and measurement of different
      clinical endpoints. CONCLUSIONS: Based on this review of the literature, there is
      a great need to develop an evidence-based approach to the use of lasers for the
      treatment of chronic periodontitis. Simply put, there is insufficient evidence to
      suggest that any specific wavelength of laser is superior to the traditional
      modalities of therapy. Current evidence does suggest that use of the Nd:YAG or
      Er:YAG wavelengths for treatment of chronic periodontitis may be equivalent to
      scaling and root planing (SRP) with respect to reduction in probing depth and
      subgingival bacterial populations. However, if gain in clinical attachment level
      is considered the gold standard for non-surgical periodontal therapy, then the
      evidence supporting laser-mediated periodontal treatment over traditional therapy
      is minimal at best. Lastly, there is limited evidence suggesting that lasers used
      in an adjunctive capacity to SRP may provide some additional benefit.

PMID- 16584336
TI  - Local drug delivery in the treatment of periodontal diseases: assessing the
      clinical significance of the results.
AB  - BACKGROUND: Local drug delivery can be used in the management of periodontal
      patients. However, statistically significant responses to therapy recorded in
      clinical trials may not be clinically significant. METHODS: Controlled clinical
      trials were selected that assessed the capability of local drug delivery to
      improve periodontal health. RESULTS: Several local drug delivery systems employed
      as monotherapies improved periodontal health and provided results that were not
      statistically significantly different than attained with scaling and root planing
      (SRP) alone. In contrast, many local drug delivery devices when used as adjuncts
      to SRP provided a statistically significant enhancement of parameters commonly
      used to monitor periodontal status. However, mean improvements with respect to
      probing depth reduction or gain of clinical attachment were often limited to
      tenths of millimeters. Several devices also achieved specific criteria that can
      be used to identify clinically significant findings (e.g., number of sites with
      probing depth reduction >or=2 mm). However, there are conflicting data with
      respect to the ability of local drug delivery to enhance results of SRP at deep
      probing sites, and there is limited information relative to its capability to
      inhibit disease progression or enhance osseous repair in infrabony defects.
      CONCLUSION: The decision to use local drug delivery during active treatment or
      maintenance should be based upon clinical findings, responses to therapy recorded
      in the literature, desired clinical outcomes, and the patient's dental and
      medical history.

PMID- 16584337
TI  - Modulation of phagocytosis, chemotaxis, and adhesion of neutrophils by areca nut
      extracts.
AB  - BACKGROUND: A higher prevalence of periodontal diseases among areca chewers than
      non-areca chewers has been demonstrated. Neutrophils, representing the first line
      of the host defense mechanism against microbial infection, play important roles
      in maintaining periodontal health. This study determined the possible effects of
      areca nut on phagocytosis, chemotaxis, and adhesion of human neutrophils.
      METHODS: Aqueous extracts of ripe areca nut without husk (rANE) and fresh and
      tender areca nut with husk (tANE) were examined for their effects on neutrophil
      phagocytosis using flow cytometry and confocal laser scanning microscopy. The
      effects of rANE and tANE on chemotaxis and adhesion of neutrophils to human
      aortic endothelial cells were examined using fluorescence-labeled neutrophils.
      RESULTS: Both rANE and tANE inhibited the phagocytic activity of neutrophils in a
      dose-dependent manner. The levels of internalized fluorescent bacteria in
      neutrophils decreased after ANE treatment. However, exposure of neutrophils to
      rANE and tANE stimulated the chemotaxis activity of neutrophils to N-formyl-Met
      Leu-Phe (fMLP) and enhanced adhesion of neutrophils to human aortic endothelial
      cells in a dose-dependent manner. Moreover, treatment of neutrophils with rANE
      was more effective than incubation with tANE. CONCLUSIONS: Components of areca
      nut inhibited phagocytosis activity of neutrophils but enhanced chemotaxis and
      adhesion of neutrophils. Alterations in functions of neutrophils may lead to
      signs of clinical diseases associated with areca chewing. The components in ANEs
      that are responsible for these observations remain to be elucidated.

PMID- 16584338
TI  - prtH in Tannerella forsythensis is not associated with periodontitis.
AB  - BACKGROUND: It has been suggested that prtH in Tannerella forsythensis encodes
      for a cystein proteinase that is associated with its pathogenic potential and can
      discriminate between periodontal health and disease. The aim of this
      investigation was to further establish this potentially important observation.
      METHODS: A group of 33 consecutive adult patients with periodontitis (mean age:
      47.6 +/- 10.1 years) harboring T. forsythensis was selected to investigate the
      presence of prtH by polymerase chain reaction (PCR). The T. forsythensis strains
      were isolated by anaerobic culture techniques. To investigate the association of
      this gene with periodontitis, a group of 14 age-matched subjects (mean age: 56.4
      +/- 6.9 years) without any signs of periodontal disease (probing depths <3 mm and
      no radiographic attachment loss) was tested for comparison. Pure isolates and
      crude subgingival plaque samples were used as a template for the PCR. RESULTS: In
      the group of 33 T. forsythensis-positive patients, we found two T. forsythensis
      isolates to be prtH negative. Despite repeated analyses, testing of the whole
      subgingival plaque samples revealed only 17 of 33 samples to be prtH positive.
      The T. forsythensis isolates from the 14 periodontally healthy subjects were all
      prtH positive. The odds ratio of the presence of prtH in T. forsythensis in
      periodontitis patients versus healthy controls is 1.06 (P >0.05). CONCLUSIONS: On
      the basis of our data, we conclude that the presence of prtH in T. forsythensis
      is not discriminative for patients with T. forsythensis-associated periodontitis
      compared to healthy carriers of T. forsythensis. In addition, the use of whole
      subgingival plaque samples to test for the prevalence of prtH in bacteria
      appeared unreliable. Culture of the microorganism is an important condition to
      receive a sufficient amount of template DNA to detect the specific locus of the
      genome.

PMID- 16584339
TI  - Clinical and metabolic changes after conventional treatment of type 2 diabetic
      patients with chronic periodontitis.
AB  - BACKGROUND: The aim of this study was to compare the response to conventional
      periodontal treatment between patients with or without type 2 diabetes mellitus
      from a clinical and metabolic standpoint. METHODS: A prospective, parallel,
      comparative longitudinal clinical study was performed between type 2 diabetics
      and non-diabetics with moderate generalized chronic periodontitis. The study
      period was 6 months. Conventional periodontal scaling and root planing were
      performed, and the response to this treatment was compared between the groups at
      3 and 6 months, measuring the plaque index, bleeding on probing, probing depth,
      level of clinical attachment, and gingival recession. In the diabetic patients,
      the clinical response was related to measurements of HbA1c and glucose in blood
      at 3 and 6 months. RESULTS: An improvement in all clinical variables was
      observed, with no statistically significant differences between the groups, with
      the exception of probing depth (P <0.0207). The improvement observed in blood
      HbA1c levels confirmed a positive metabolic response to periodontal treatment,
      with a lower value for this variable at each measurement time. CONCLUSIONS: Both
      groups of patients showed a clinical improvement after basic non-surgical
      periodontal treatment. The diabetic patients showed improved metabolic control
      (lower HbA1c) at 3 and 6 months after periodontal treatment.

PMID- 16584340
TI  - Effect of cigarette smoke inhalation and estrogen deficiency on bone healing
      around titanium implants: a histometric study in rats.
AB  - BACKGROUND: It has been shown that cigarette smoke inhalation (CSI) and estrogen
      deficiency (OVX) may affect bone quality around titanium implants; however, their
      association has not been evaluated. Therefore, this study aimed to verify the
      effects of CSI associated with OVX on bone healing around titanium implants.
      METHODS: The tibia surface of 45 female Wistar rats was surgically exposed, and
      screw-shaped titanium implants were placed. The animals were randomly assigned to
      OVX (ovariectomized rats; n = 15), SHAM (sham-operated rats; n = 15), and CSI +
      OVX (4 months of intermittent cigarette smoke inhalation, starting 2 months
      before implant placement in ovariectomized rats; n = 15). The implants were
      placed at the time of OVX or SHAM surgery. After 60 days, the animals were
      sacrificed and undecalcified sections obtained. The percentages of mineralized
      tissue (bone density [BD]) in a 500-microm-wide zone lateral to the implant, bone
      filling (BF) within the limits of the threads, and bone-to-implant contact (BIC)
      were measured in cortical (zone A) and cancellous (zone B) bone. RESULTS: In zone
      A, the CSI + OVX group showed a significant difference regarding BIC and BD (P
      <0.05) compared to the other groups. In zone B, data analysis showed that the CSI
      + OVX group presented the lowest percentage of BD and BIC, followed by the OVX
      and SHAM groups, respectively (P <0.05). CONCLUSION: Within the limits of the
      present study, it can be concluded that cigarette smoke inhalation amplified the
      deleterious effects of estrogen deficiency, affecting both preexisting and newly
      formed bone in the cortical and cancellous bone around titanium implants.

PMID- 16584341
TI  - Locally delivered doxycycline as an adjunctive therapy to scaling and root
      planing in the treatment of smokers: a 2-year follow-up.
AB  - BACKGROUND: The aim of this clinical study was to evaluate the association of
      locally delivered doxycycline 10% with scaling and root planing in the
      periodontal treatment of smokers during a 2-year period. METHODS: Forty-eight
      chronic periodontitis patients, presenting a minimum of four pockets (>or=5 mm)
      that bled on probing on anterior teeth were included. Patients were randomly
      assigned to receive one of the following treatments: scaling and root planing
      (SRP) and scaling and root planing followed by local application of doxycycline
      (SRP-D). Assigned treatments were performed at baseline and at 12 months.
      Clinical parameters, including probing depth (PD) and relative attachment level
      (RAL), were recorded at baseline; 45 days; 3, 6, and 12 months (retreatment); 45
      days following retreatment; and at 15, 18, and 24 months. RESULTS: In initially
      deep pockets (>or=7 mm), SRP-D showed greater PD reduction than SRP at 6 and 18
      months (mean difference between groups of 1.18 and 1.73 mm, respectively; P
      <0.05) and greater RAL gain in all periods after 3 months (mean difference
      between groups of 1.16, 1.99, and 1.78 mm, at 6, 18, and 24 months, respectively;
      P <0.05). Also, the proportion of sites showing >or=2 mm PD reduction was greater
      for SRP-D at 6 months (81.2% x 50.8%; P <0.001) and at 24 months (65.5% x 46.5%;
      P = 0.01). As for RAL gain, this proportion was 34.4% and 18.1% for SRP-D and SRP
      at 24 months, respectively (P = 0.008). CONCLUSION: The use of locally delivered
      doxycycline may constitute an important adjunct for the active and supportive
      treatments of severe periodontal disease in smokers.

PMID- 16584342
TI  - Influence of the interimplant distance on crestal bone resorption and bone
      density: a histomorphometric study in dogs.
AB  - BACKGROUND: The position of gingival soft tissues depends on the position and
      health of the underlying alveolar bone. The aim of this study was to evaluate the
      influence of different interimplant distances on crestal bone resorption after
      prosthetic restoration with a 5-mm distance between the contact point and the
      bone crest. METHODS: The mandibular bilateral premolars of six dogs were
      extracted and, after 12 weeks, each dog received eight implants, totaling 48
      implants in the experiment. Two pairs, one in each hemiarch, were separated by 2
      mm (group 1) and two by 3 mm (group 2). After 12 weeks, the implants received
      temporary acrylic prostheses. After 4 more weeks, metallic crowns substituted the
      temporary prostheses. After 4 more weeks, the animals were sacrificed, and their
      hemimandibles were removed, dissected, and processed. RESULTS: For groups 1 and
      2, respectively, the mean of interimplant bone resorption (IIBR) analyzed
      histologically was 2.03 and 1.98 mm (P >or=0.05), and the mean of the distal
      extension bone resorption was 2.04 and 1.92 mm for groups 1 and 2, respectively
      (P >or=0.05). The crestal bone resorption between the implants was 0.13 mm (P
      >or=0.05) for both groups. The mean of IIBD for groups 1 and 2 was 79% and 80%,
      respectively. When the IIBD was compared to the distal extension bone density for
      group 1 (79% and 64%) and group 2 (80% and 62%), statistically significant
      differences were obtained for both groups (P <or=0.05). CONCLUSIONS: The
      distances of 2 and 3 mm between implants do not result in statistically
      significant differences in crestal bone resorption around implant surfaces in
      dogs. The bone density is enhanced when loading is present at the interimplant
      area.

PMID- 16584343
TI  - Gene expression in splenic CD4 and CD8 cells from BALB/c mice immunized with
      Porphyromonas gingivalis.
AB  - BACKGROUND: T cells are fundamental in the pathogenesis of periodontal disease.
      Suppression of cell-mediated responses is associated with disease progression
      together with the concomitant increase in plaque pathogens including
      Porphyromonas gingivalis. The aim of the present study was to examine gene
      expression in T cells in response to P. gingivalis in mice. METHODS: BALB/c mice
      were given weekly intraperitoneal injections of P. gingivalis outer-membrane
      antigens with Freund's incomplete adjuvant for 3 weeks, whereas control mice
      received phosphate buffered saline (PBS) and adjuvant only. Splenic CD4 and CD8
      subpopulations were isolated by magnetic cell separation and their responses
      investigated using microarray analysis. RESULTS: Most genes coded for enzymes
      concerned with metabolic pathways. Only five and 28 genes, respectively, were
      upregulated in CD4 and CD8 cells extracted from P. gingivalis-immunized mice,
      including immunoglobulin (Ig) heavy-chain genes for IgG1 and IgG2a in CD4 cells.
      In contrast, 1,141 and 1,175 genes, respectively, were downregulated. A total of
      60 and 65 genes, respectively, coded for immune response proteins or those
      relevant to periodontal disease pathogenesis. The overlap of genes in the two
      subsets was 21%. One of the major effects, apart from T-cell function
      suppression, was the shift away from Th1 responses, although there was also a
      downregulation of two genes and upregulation of one Th2-response gene. Genes
      downregulated included those encoding cytokines, proteins involved in Ig binding,
      antigen presentation, innate immunity, extracellular matrix, and cell adhesion
      molecules that could result in dysregulation in the progressive periodontal
      lesion. CONCLUSIONS: Early findings in humans demonstrated that periodontopathic
      bacteria induce immunosuppressive effects on T cells. The present study has shown
      that P. gingivalis had a predominant downregulatory effect on gene expression in
      CD4 and CD8 T cells in mice.

PMID- 16584344
TI  - Gingival crevicular fluid leptin levels in periodontitis patients with long-term
      and heavy smoking.
AB  - BACKGROUND: The aim of the present study was to evaluate gingival crevicular
      fluid (GCF) leptin levels and the influence of long-term and heavy smoking on GCF
      leptin levels in patients with chronic periodontitis. METHODS: In this study, 143
      individuals were divided into three groups: non-smokers (NS), smokers (S), and
      control (C). Three subgroups of NS and S were grouped as follows: a) probing
      depth (PD) <or=3 mm; b) PD = 4 to 5 mm; and c) PD >5 mm. For each patient, PD,
      gingival index (GI), plaque index (PI), gingival bleeding time index (GBTI), and
      clinical attachment level (CAL) values were recorded. The GCF leptin levels
      obtained from sampling sites were determined by using enzyme-linked immunosorbent
      assay kits. RESULTS: The GCF leptin levels were found significantly lower in the
      a and b subgroups in the S group than those in the NS group (P <0.05). The
      inflammatory markers GI and GBTI showed significant correlations with leptin in
      NS (P <0.05). CONCLUSIONS: Our results suggest that higher leptin GCF levels in
      healthy sites in periodontitis patients may play a protective role in periodontal
      disease. Further studies are needed to determine the cellular origin of the
      leptin in the gingiva and the effect of plasma leptin levels on GCF leptin
      concentrations.

PMID- 16584345
TI  - Factors influencing treatment outcomes in mandibular Class II furcation defects.
AB  - BACKGROUND: Factors influencing treatment outcomes in furcation defects remain to
      be studied. Therefore, the aim of the study was to evaluate the association
      between factors and clinical parameters that may influence treatment outcomes in
      mandibular Class II furcation defects. METHODS: Twenty-seven systemically healthy
      subjects with a Class II buccal or lingual furcation defect in lower molars were
      treated. Clinical measurements (probing depth [PD], clinical attachment level
      [CAL], recession, mobility, plaque index [PI], and bleeding on probing [BOP]) and
      defect (vertical and horizontal defect depths) were obtained at initial and 6
      month reentry surgeries. Treatment modalities (e.g., nine each in the following
      three groups: open flap debridement [OFD] alone, bone graft [BG], and bone graft
      plus a bioabsorbable collagen membrane [BG + C]), anatomic factors (presence of
      cervical enamel projection, presence of cervical restorations/fixed prosthesis,
      and location of furcations [buccal or lingual sides; first or second molars]),
      clinical parameters (initial mobility, initial PD at furcation, initial CAL at
      furcation, mean initial PD of the tooth, mean initial CAL of the tooth, initial
      horizontal PD at furcation, initial horizontal/vertical defect depth, PI, and
      BOP), and background factors (endodontic status, smoking status, and surgeon's
      experience) were analyzed for associations with probability of clinical
      improvement. RESULTS: The anatomic factors, clinical parameters, and background
      information were found to have no effect in influencing treatment outcome with
      the exception of initial vertical defect depth. An initial vertical defect depth
      >or=4 mm had a borderline significance (P = 0.06) of achieving a high probability
      of having a 1-mm vertical bone fill. In addition, treatment modality was found to
      be a major influence factor. Sites treated with BG were 16x more likely to have
      >50% vertical bone fill than open flap surgery. Furthermore, sites treated with
      BG were 64x more likely to have a 1-mm vertical defect fill compared to sites
      treated with OFD and 16x more likely to have a 2-mm vertical defect fill compared
      to sites treated with OFD or BG + C. However, the additional membrane does not
      enhance the regenerative outcomes achieved by BG alone. CONCLUSIONS: Initial
      vertical defect depth (>or=4 mm) and treatment modality (e.g., BG) were found to
      be the clinical parameter and factor that were associated with high probability
      of clinical improvement. Sites treated with BG, such as mineralized human
      cancellous allograft, were more likely to have greater vertical furcation defect
      fill than the conventional OFD surgery. Additional membrane placement does not
      enhance the treatment outcome achieved by BG alone.

PMID- 16584346
TI  - Upregulation of the expression of epidermal growth factor and its receptor in
      gingiva upon cyclosporin A treatment.
AB  - BACKGROUND: To understand the roles of epidermal growth factor (EGF) and EGF
      receptor (EGF-R) in cyclosporin A (CsA)-induced gingival overgrowth, expression
      of EGF and EGF-R upon CsA treatment was examined in an oral epidermoid carcinoma
      cell line of humans (OECM-1) and in edentulous gingiva of rats. METHODS: In vitro
      study: after CsA treatment, OECM-1 cells were harvested to evaluate their mRNA
      and protein expression of EGF and EGF-R with reverse transcriptase-polymerase
      chain reaction (RT-PCR), Western blot, and immunocytochemistry (ICC). In vivo
      study: 3 weeks after extraction of all maxillary molars, 20 male Sprague-Dawley
      rats were assigned to a CsA group (30 mg/kg, fed daily) and a control group. Five
      rats per group were sacrificed at weeks 1 and 4. Edentulous ridge specimens were
      obtained for evaluating their mRNAs and protein expression with RT-PCR, real-time
      RT-PCR, and immunohistochemistry (IHC). In both in vitro and in vivo experiments,
      the proliferating potential of epithelial cells was examined by the presence of
      proliferating cell nuclear antigen (PCNA). RESULTS: In vitro: dose-dependently
      increased mRNA expression of EGF and EGF-R in OECM-1 cells was noted after CsA
      treatment. Protein expressions of EGF and EGF-R were higher in OECM-1 with CsA
      treatment than without CsA. In vivo: higher mRNA and protein expressions of EGF
      and EGF-R were also observed in the gingival tissues of CsA-treated rats. In both
      in vitro and in vivo experiments, greater PCNA expression after CsA treatment was
      demonstrated. CONCLUSIONS: Higher expression of EGF and EGF-R upon CsA therapy
      was observed in OECM-1 epithelial cells of humans and in edentulous gingiva of
      rats. We suggest that CsA could upregulate gene and protein expression of EGF and
      EGF-R, and the upregulation may play a role in gingival overgrowth.

PMID- 16584347
TI  - Effects of selective cyclooxygenase-2 inhibitor and omega-3 fatty acid on serum
      interleukin-1beta, osteocalcin, and C-reactive protein levels in rats.
AB  - BACKGROUND: The aim of this study was to evaluate the effects of selective
      cyclooxygenase-2 inhibitor, celecoxib, and omega-3 fatty acid on serum levels of
      interleukin 1-beta (IL-1beta), osteocalcin (OC), and C-reactive protein (CRP) in
      experimental periodontitis. METHODS: Experimental periodontitis in rats was
      induced by repeated injection of purified lipopolysaccharide (LPS) derived from
      Escherichia coli endotoxin. Forty-seven adult male Sprague-Dawley rats were
      divided into five study groups as follows: saline control, LPS, LPS + celecoxib,
      LPS + omega-3 fatty acid, and LPS + celecoxib + omega-3 fatty acid. Celecoxib and
      omega-3 fatty acid were given alone or in combination during 14 days of the
      experimental study period. At the end of the 2-week protocol, serum samples were
      obtained, and the rats were sacrificed. Serum samples were analyzed for IL-1beta,
      OC, and CRP concentrations by enzyme-linked immunosorbent assay. Defleshed jaws
      were analyzed morphometrically for alveolar bone loss. Data were evaluated
      statistically by non-parametric tests. RESULTS: According to the morphometric
      measurements, the LPS and drug treatment groups showed significantly higher bone
      loss than the saline control group (P <0.05). Omega-3 fatty acid, both alone and
      in combination with celecoxib, revealed significantly higher IL-1beta levels than
      LPS and celecoxib groups (P <0.05). Individual and combined administration of
      celecoxib and omega-3 fatty acid significantly increased OC levels compared to
      the LPS group (P <0.05). There were no significant differences in serum CRP
      levels. CONCLUSIONS: Celecoxib and/or omega-3 fatty acid administration does not
      significantly influence circulating levels of CRP. The significantly increased
      serum OC level observed after individual and combination administration suggests
      that celecoxib and omega-3 fatty acid may influence bone remodeling and thereby
      inhibit the progression of alveolar bone resorption. However, the failure to
      observe any significant inhibition of bone loss in celecoxib- and/or omega-3
      fatty acid-treated rats compared to the LPS group suggests that their therapeutic
      effect may be reduced by other factors, such as increases in serum IL-1beta
      promoting osteoclast activity.

PMID- 16584348
TI  - Gingival crevicular fluid matrix metalloproteinase-25 and -26 levels in
      periodontal disease.
AB  - BACKGROUND: Tissue destruction associated with the progression of periodontal
      disease is caused by a cascade of host and microbial proteolytic enzymes. Host
      derived matrix metalloproteinases (MMPs) play an important role in the
      degradation of the extracellular matrix. Leukolysin/membrane-type 6 (MT-6)/MMP
      25, the latest member of the MT-MMP subgroup of the MMP family, is primarily
      expressed by neutrophils and involved in extracellular matrix turnover.
      Matrilysin-2/MMP-26 (endometase), a novel member of the matrilysin subgroup of
      the MMP family, can degrade the extracellular matrix, alpha1-antitrypsin, and
      activate pro-MMP-9. Our study aimed to examine the levels, molecular forms, and
      degrees of activation of MMP-25 and MMP-26 in gingival crevicular fluid (GCF)
      from patients with different periodontal diseases. METHODS: A total of 105
      subjects, 35 with generalized aggressive periodontitis (GAgP), 29 with chronic
      periodontitis (CP), 20 with gingivitis, and 21 periodontally healthy subjects,
      were included in this study. Periodontal status was evaluated by measuring
      probing depth, clinical attachment loss, presence of bleeding on probing, and
      plaque. GCF MMP-25 and MMP-26 levels were analyzed by computer-quantitated
      Western immunoblotting using specific antibodies. RESULTS: The 57-kDa soluble pro
      MMP-25 and 45- to 47-kDa active form of MMP-25 were detected by Western
      immunoblots in CP and GAgP GCF, and lesser levels of these soluble MMP-25
      immunoreactive bands were detected in gingivitis GCF. An enhanced and similar
      degree of MMP-25 activation was found in GAgP, CP, and gingivitis groups. There
      were no detectable MMP-25 immunoreactivities in the healthy subjects' GCF. GAgP
      and CP groups had elevated GCF MMP-26 levels and degrees of activation compared
      to the gingivitis and healthy groups (P <0.008). The gingivitis group had higher
      GCF MMP-26 levels and degree of activation compared to the healthy group (P
      <0.008). CONCLUSIONS: The present study demonstrated the presence of soluble or
      shed forms of MMP-25 and MMP-26 in GCF of patients with different periodontal
      diseases. Increased levels and activation of MMP-25 and MMP-26 in GCF are
      associated with an enhanced severity of periodontal inflammation, suggesting that
      these novel MMPs can participate in the progression of periodontal diseases. They
      may prove to be diagnostically useful and could be targets of medication in the
      future.

PMID- 16584349
TI  - Fabrication of cultured oral gingiva by tissue engineering techniques without
      materials of animal origin.
AB  - BACKGROUND: Cultured gingival substitute has been found to be a useful graft
      material for treatment of gingival recession. However, such substitutes include
      xenograft derivative materials that involve concomitant risk of viral
      contamination. To eliminate this risk, we designed new gingival substitutes made
      of recombinant human collagen types I and III sponges and cultured these
      substitutes in animal-free media (HFDM-1). METHODS: Gingival fibroblasts were
      seeded onto sponges of type I or III recombinant collagen. These sponges were
      cultured in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum
      (FBS), HFDM-1 with 2% human serum (HS), or HFDM-1. Fibroblast proliferation in
      these samples was compared using the cell-counting kit assay. Vascular
      endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) released into
      the cultured media were examined by enzyme-linked immunosorbent assay. RESULTS:
      The fibroblasts proliferated significantly in all six combinations of collagen
      and medium types. The fibroblast growth rate after 9 days of culture was equal
      between HFDM-1 with 2% HS and DMEM with 10% FBS. The type III collagen sponge
      showed a higher fibroblast growth rate than the type I sponge. VEGF
      concentrations in HFDM-1 with 2% HS were higher than those in other media. The
      highest HGF levels were detected in DMEM with 10% FBS. CONCLUSIONS: The new
      cultured gingival substitute containing no animal-derived materials produced good
      cell proliferation and VEGF release. The results suggested that the substitute
      may provide a new tool for the treatment of gingival recession.

PMID- 16584350
TI  - Surgical or non-surgical periodontal treatment: factors affecting patient
      decision making.
AB  - BACKGROUND: This study explored which factors affected patients' decisions to
      pursue either surgical or non-surgical periodontal treatment. METHODS: Data were
      collected from 74 patients at a regularly scheduled periodontal appointment, at
      which each patient was told that periodontal treatment was needed, and 2 weeks
      following the actual treatment. The surveys assessed the patients' decisions and
      potential determinants of these decisions. The dental anxiety scale-revised, the
      state-trait anxiety inventory, and the Iowa dental control index were used to
      measure psychosocial factors. RESULTS: Patients who decided to have surgery did
      not differ from patients who decided against surgery in sociodemographic
      variables such as gender, age, education, and socioeconomic status, nor in their
      desire for control over the treatment decision. However, they had less dental
      fear and less general anxiety than the non-surgery patients. Although the two
      patient groups did not differ in their responses concerning how well the dentists
      had informed them about the procedure, they differed in the degree of trust and
      rapport with their dentists. CONCLUSIONS: The less dentally fearful and anxious
      patients were in general and the more they trusted their provider and felt they
      had good rapport, the more likely they were to accept surgical periodontal
      treatment. These results stress the importance of good patient-provider
      communication.

PMID- 16584351
TI  - Porphyromonas gingivalis-induced cellular hypertrophy and MMP-9 activity via
      different signaling pathways in H9c2 cardiomyoblast cells.
AB  - BACKGROUND: Little is known about the pathogenesis of cardiomyocyte hypertrophy
      caused by periodontitis pathogens. The purpose of this study was to determine the
      effect of the periodontal pathogen Porphyromonas gingivalis on cardiomyocyte
      hypertrophy. METHODS: Matrix metalloproteinase (MMP)-2 and MMP-9 activities and
      cellular morphology were measured by gelatin zymography and immunofluorescence
      after P. gingivalis-medium treatment with or without SB203580 (p38 mitogen
      activated protein kinase cascade [p38] inhibitor), U0126 (mitogen-activated
      protein kinase kinase [MAPKK] inhibitor), LY294002 (phosphoinositide 3-kinase
      [PI3K] inhibitor), cyclosporin A (CsA; calcineurin inhibitor), SP600125 (c-Jun N
      terminal kinase [JNK] inhibitor), proinflammatory interleukin (IL)-1, or anti
      inflammatory IL-10 in cultured cardiomyoblast H9c2 cells. RESULTS: P. gingivalis
      medium increased MMP-9 activities and cellular sizes (+87%) of H9c2 cells,
      whereas Actinobacillus actinomycetemcomitans medium and Prevotella intermedia
      medium had no effects. The increased activity of MMP-9 treated with P. gingivalis
      medium was not mediated through p38, extracellular-regulated kinase (ERK), PI3K,
      calcineurin, and JNK signaling pathways and was not inhibited by IL-10. However,
      the hypertrophy of H9c2 cells induced with P. gingivalis medium was reduced by
      administration of SB203580 (-37%), U0126 (-35%), LY294002 (-49%), CsA (-49%), and
      SP600125 (-24%). CONCLUSIONS: Our findings suggest that P. gingivalis medium
      elevated MMP-9 activity and induced cardiomyoblast hypertrophy. However, P.
      gingivalis-induced H9c2 cell hypertrophy was mediated through p38, ERK, PI3K,
      calcineurin, and JNK signaling pathways, which are in a totally different
      regulatory pathway from P. gingivalis-elevated MMP-9 activity. These findings
      provide evidence that P. gingivalis infection activated multiple factors via
      different pathways to induce the development of hypertrophy of H9c2
      cardiomyoblast cells.

PMID- 16584352
TI  - Are dental plaque, poor oral hygiene, and periodontal disease associated with
      Helicobacter pylori infection?
AB  - BACKGROUND: The microorganism Helicobacter pylori has been closely linked to
      chronic gastritis, peptic ulcer, gastric cancer, and mucosa-associated lymphoid
      tissue (MALT) lymphoma. Despite the current treatment regimens that lead to
      successful management of H. pylori-positive chronic gastritis, the reinfection
      rate is high. It has been suggested that one of the possible mechanisms of
      reinfection is the recolonization from dental plaque. The purpose of this study
      was to determine whether dental plaque, poor oral hygiene, and periodontal
      disease were risk factors for H. pylori infection. METHODS: Among the 134
      patients, 65 patients who had a positive H. pylori serology or positive rapid
      urease test or histologic evidence for the presence of H. pylori in antral biopsy
      specimens were categorized as cases. The remaining 69 patients who were negative
      for H. pylori serology, the rapid urease test, and histology were controls.
      RESULTS: It was found that the association of periodontal disease and poor oral
      hygiene with H. pylori infection was not significant. There was a higher
      prevalence of H. pylori in the dental plaque of patients with gastric H. pylori
      infection than in controls, but both groups had a surprisingly high positive
      urease test for H. pylori in plaque (89% and 71%, respectively). CONCLUSIONS: H.
      pylori in dental plaque is seldom eliminated by H. pylori-eradication therapy,
      and this may act as a source for future reinfection. Hence, eradication of H.
      pylori from the dental plaque should be made an important part of comprehensive
      management of H. pylori-associated gastric diseases.

PMID- 16584353
TI  - Bone marrow stromal cells of young and adult rats respond similarly to platelet
      released supernatant and bone morphogenetic protein-6 in vitro.
AB  - BACKGROUND: Age-related changes in periodontal bone regeneration,
      osseointegration of dental implants, and graft consolidation are increasingly
      considered in treatment planning. This study was intended to show whether aging
      is associated with a diminished responsiveness of osteoprogenitor cells to growth
      and differentiation factors. METHODS: We compared the capacity of bone marrow
      stromal cells harvested from young and adult rats to proliferate, migrate, and
      differentiate into the osteogenic lineage following exposure to platelet-released
      supernatant (PRS) or bone morphogenetic protein-6 (BMP-6). Bone marrow stromal
      cells were isolated from 12 young rats aged 6 weeks and 12 adult rats aged 9
      months. Proliferation was assessed by 3[H]thymidine incorporation, migration was
      evaluated with the Boyden chamber assay, and osteogenic differentiation was
      deduced from alkaline phosphatase activity. RESULTS: Irrespective of the donor
      age, bone marrow stromal cells showed increased mitogenic activity and
      chemotactic motility when exposed to PRS. Adult bone marrow stromal cells had
      higher alkaline phosphatase activities at baseline and upon incubation with BMP-6
      than cells obtained from young animals. There was no difference between the two
      groups in the slope of the alkaline phosphatase activity curve following
      stimulation with BMP-6. CONCLUSIONS: The data demonstrate that, irrespective of
      their age, bone marrow stromal cells respond similarly to PRS and BMP-6 under in
      vitro conditions. These findings suggest that osteoprogenitor cells within the
      bone marrow of adult rats retain their juvenile potential to respond to growth
      and differentiation factors, which are released naturally or are applied
      therapeutically at sites of bone regeneration.

PMID- 16584354
TI  - Enamel matrix derivative and systemic antibiotics as adjuncts to non-surgical
      periodontal treatment: biologic response.
AB  - BACKGROUND: Short-term clinical observations suggest an anti-inflammatory effect
      of enamel matrix derivative (EMD). The purpose of this study was to evaluate the
      anti-inflammatory capacity of EMD, used as an adjunct to non-surgical periodontal
      treatment of deep lesions in chronic periodontitis patients, by monitoring
      inflammatory markers in gingival crevicular fluid (GCF). METHODS: Sixteen
      subjects were randomly assigned to treatment with EMD or placebo in contralateral
      dentition areas. Half of the subjects received 250 mg metronidazole and 375 mg
      amoxicillin three times a day for 7 days; the other half received a placebo. GCF
      samples were collected from one interproximal lesion in each of the contralateral
      quadrants before treatment and after 10 days and 2, 6, and 12 months. Total
      protein content was determined according to the Bradford method. Myeloid-related
      protein (MRP) 8/14 and interleukin (IL)-1beta were analyzed quantitatively by
      enzyme-linked immunosorbent assay (ELISA), and elastase activity was determined
      using a low molecular weight fluorogenic substrate. RESULTS: No significant
      differences were observed between sites treated with or without EMD for any
      biochemical parameter. Two months after treatment, subjects treated with
      antibiotics exhibited less clinical signs of inflammation. Furthermore, these
      subjects had lower MRP 8/14 levels only at day 10 compared to those receiving the
      placebo. For total protein, IL-1beta, and elastase, no statistically significant
      differences were noted for subjects with or without antibiotic therapy at any
      time point. CONCLUSIONS: Improved healing of the soft tissues has been noted
      clinically in non-surgically treated sites in subjects treated with antibiotics.
      The expression of inflammatory mediators in GCF corroborated this finding only in
      part. EMD did not seem to further affect the expression of inflammatory
      mediators.

PMID- 16584355
TI  - Clinical and anatomical factors limiting treatment outcomes of gingival
      recession: a new method to predetermine the line of root coverage.
AB  - Complete root coverage is not always achievable, even in gingival recession with
      no loss of interproximal attachment and bone. The cemento-enamel junction is the
      most widely used referring parameter to evaluate root coverage results. The aim
      of the present study was to describe the most frequent diagnostic mistakes that
      may lead to incomplete root coverage in Miller Class I and II gingival recessions
      and to suggest a method to predetermine the level/line of root coverage in non
      molar teeth. The line of root coverage (i.e., the level/line to which the soft
      tissue margin will be positioned after the healing process of a root coverage
      surgical technique) was predetermined by calculating the ideal vertical dimension
      of the interdental papilla of the tooth with the recession defect. This method
      was applied to 120 recession-type defects affecting non-molar teeth of 80 young
      healthy subjects that were treated with root coverage surgical procedures over
      the last 5 years. All recessions were Miller Class I or II and were associated
      with at least one of the following characteristics: 1) traumatic loss of the tip
      of the interdental papilla(e); 2) tooth rotation; 3) tooth extrusion with or
      without occlusal abrasion; and 4) a cervical abrasion defect with no evidence of
      the cemento-enamel junction. The line of root coverage may be considered the
      clinical cemento-enamel junction because it may substitute the anatomic cemento
      enamel junction when this is no longer clinically visible on the tooth with
      recession or when the ideal conditions to obtain complete root coverage are not
      fully represented.

PMID- 16584356
TI  - Clinical outcome of implants placed immediately after implant removal.
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical success of
      implants placed immediately after the explantation of failed implants due to
      fracture at 12 months. METHODS: Nine immediate implants were placed in nine
      patients following explantation of nine fractured implants. Five experimental
      implants did not require any regenerative procedures; the remaining four
      immediate implants were grafted with deproteinized porcine bone particles and
      covered with bioabsorbable membranes. All implants were restored with fixed
      prostheses. The follow-up period was 12 months. RESULTS: No residual bone defects
      were observed or probed around any implant at the second-stage surgery, and all
      implants were asymptomatic and stable. All the implants were successful after
      prosthetic rehabilitation showing no mobility, pain, suppuration, or absence of
      peri-implant radiolucency. The radiographic measurements showed no significant
      bone loss pattern at the 12-month follow-up visit. CONCLUSION: The findings of
      this study suggested that implants placed immediately after implant explantation
      due to biomechanical fracture could be performed with results that are similar to
      results obtained with implants placed immediately after tooth extraction.

PMID- 16584357
TI  - Langerhans' cell histiocytosis in a 5-year-old girl: evidence of periodontal
      pathogens.
AB  - BACKGROUND: Langerhans' cell histiocytosis (LCH) is a rare disorder characterized
      by Langerhans' cell proliferation in various organs or tissues. When periodontal
      tissue is involved, clinical manifestations can vary from gingival recession and
      pocket formation to severe alveolar bone loss. This case report describes
      periodontal pathogens found in the pockets of involved primary teeth. METHODS: A
      5-year-old girl with LCH presented with loose teeth. Intraoral examination and
      radiographs revealed deep pockets and severe bone loss around all primary molars.
      Bacterial samples were obtained from saliva and subgingival plaque and analyzed
      for the presence of five periodontopathic bacteria using a polymerase chain
      reaction (PCR) method. Due to severe periodontal destruction, all primary molars
      were extracted, and a gingival biopsy was taken from tooth T to confirm the
      diagnosis of LCH. RESULTS: The biopsy specimen revealed the histologic features
      of LCH. The patient was diagnosed as having periodontitis as a manifestation of
      LCH. PCR results of subgingival plaque from LCH-affected molars indicated the
      presence of Porphyromonas gingivalis, Tannerella forsythensis, Treponema
      denticola, and Prevotella intermedia. However, Actinobacillus
      actinomycetemcomitans was absent from these teeth. No tested bacteria were found
      in the non-affected anterior teeth. CONCLUSIONS: The bacteria commonly associated
      with periodontal disease were detected in subgingival plaque samples from this
      LCH patient. More microbiological data are required to understand the role of
      these bacteria in LCH-associated periodontal destruction.

PMID- 16584358
TI  - Initial presentation of lung sarcomatoid carcinoma as a metastatic lesion in the
      mandibular gingiva.
AB  - BACKGROUND: Sarcomatoid carcinoma of the lung is a very rare type of tumor
      characterized by distant metastasis. However, metastasis to the gingiva is an
      uncommon event. Occasionally, an oral metastatic lesion may be the preliminary
      clinical feature observed before the diagnosis of the primary tumor. METHODS: The
      clinical features of gingival metastasis as an initial presentation of lung
      sarcomatoid carcinoma are discussed. A 55-year-old male patient presented with a
      rapidly growing pedunculated exophytic mass on the gingiva at the left side of
      the lower jaw. Incisional biopsy was performed. RESULTS: The histologic and
      immunohistochemical diagnosis was metastatic carcinoma. To locate the primary
      tumor, we analyzed the lung lesion by chest computerized tomography (CT) scans
      and biopsy. The patient was ultimately diagnosed with sarcomatoid carcinoma of
      the lung with gingival metastasis. Palliative chemotherapy for lung cancer was
      administered. The gingival lesion disappeared after chemotherapy. CONCLUSION:
      Although this case is unusual, periodontists should recognize that gingival
      masses similar to benign or inflammatory lesions may represent an initial sign of
      underlying malignant tumors.

PMID- 16584359
TI  - Oral post-surgical complications following the administration of bisphosphonates
      given for osteopenia related to malignancy.
AB  - BACKGROUND: This case report seeks to illustrate the clinical consequences of the
      administration of bisphosphonate therapy to prevent osteopenia secondary to
      malignancy in one patient. METHODS: A 69-year-old white female with a history of
      breast cancer with metastasis presented with pain in the upper left quadrant and
      periodontal pocketing of at least 6 mm in each of the four quadrants of the oral
      cavity. One week following surgery on the lower right region, lingual bone
      exposure was noted, and several attempts at achieving healing over the course of
      15 months proved unsuccessful. RESULTS: Upon referral to a surgeon at the
      Louisiana State University Medical Center, New Orleans, Louisiana, a potential
      causative factor was finally identified. The drug zoledronic acid, a
      bisphosphonate given for prevention of osteoclastic activity of bone metastasis,
      secondary to breast cancer, was identified as the possible cause of inhibition of
      healing, most likely from regional vascular insufficiency. The drug was
      immediately discontinued. The patient is healing very slowly with the aid of
      hyperbaric therapy; she has been unable to achieve smoking cessation, which is
      deterring thorough healing of the exposed bony area on the lower right lingual
      side. CONCLUSIONS: Physicians and dentists alike must become increasingly aware
      of impaired oral healing following the use of bisphosphonates given for
      malignancy-related osteopenia. A dental exam should be performed before
      bisphosphonate therapy, as recommended for radiation therapy related to
      malignancy.

PMID- 16584360
TI  - Periodontal disease in patients from the original Kostmann family with severe
      congenital neutropenia.
AB  - BACKGROUND: Patients with Kostmann syndrome (severe congenital neutropenia [SCN])
      typically normalize their absolute neutrophil count (ANC) upon granulocyte colony
      stimulating factor (G-CSF) therapy. However, although they no longer experience
      life-threatening bacterial infections, they frequently still have recurrent
      gingivitis and even severe periodontitis, often starting in early childhood.
      METHODS: We studied the periodontal disease in the four surviving patients
      belonging to the family originally described by Kostmann. Their odontological
      records, x-rays, color photos, bacterial cultures, serum antibodies to oral
      bacteria, and histopathological examinations were reviewed. The data were also
      correlated to previous investigations on their antibacterial peptides and
      molecular biology. RESULTS: Three patients had periodontal disease, despite
      normal ANC and professional dental care, and had neutrophils deficient in
      antibacterial peptides. One of these patients also had a heterozygous mutation in
      the neutrophil elastase gene, had severe periodontal disease and overgrowth of
      the periodontal pathogen Actinobacillus actinomycetemcomitans in the dental
      flora, and 15 permanent teeth had been extracted by the age of 27. One bone
      marrow-transplanted patient had no periodontal disease. CONCLUSIONS: Normalized
      ANC levels are not sufficient to maintain normal oral health in SCN patients, and
      because neutrophils are important for first-line defense and innate immunity, the
      deficiency of the antibacterial peptide LL-37 probably explains their chronic
      periodontal disease. Professional dental care is still important for SCN
      patients, despite treatment with G-CSF and normal ANC levels. Whether
      antibacterial peptides play a role in the pathogenesis of periodontitis in other
      patients remains to be elucidated.

PMID- 16584361
TI  - Adverse drug events: counting is not enough, action is needed.

PMID- 16584362
TI  - DAFNE (Dose Adjustment for Normal Eating): structured education in insulin
      replacement therapy for type 1 diabetes.

PMID- 16584363
TI  - Medical education in Australia: changes are needed.

PMID- 16584364
TI  - Adverse drug events in general practice patients in Australia.
AB  - OBJECTIVE: To investigate the frequency, cause, and severity of adverse drug
      events (ADEs) among general practice patients. DESIGN: Between May 2003 and
      February 2004, a subsample of 282 general practitioners in the BEACH (Bettering
      the Evaluation And Care of Health) data collection program recorded patient
      responses to questions about ADEs. MAIN OUTCOME MEASURES: Frequency, cause, and
      severity of ADEs; and frequency of hospitalisation and proportion of events that
      were preventable. RESULTS: From 8215 encounters, GPs reported that 852 patients
      (10.4%) had experienced an ADE in the previous 6 months. Patients aged over 45
      years (versus under 45 years), children aged 1-4 years (versus older children),
      and female patients (versus male patients) were significantly more likely to have
      experienced an ADE. Most patients (83.5%) had experienced only one ADE, with
      10.7% and 5.8% experiencing two and three or more events, respectively. For 71.9%
      of patients, one reason for the most recent event was a recognised side effect,
      followed by drug sensitivity (12.4%) and allergy (11.0%). Over half of patients
      were rated as having a "mild" event, with 35.8% rated as "moderate", and 10.0% as
      "severe". GPs classified 23.2% of events as preventable, and 7.6% of events
      resulted in hospitalisation. CONCLUSION: Our study reveals the high frequency of
      ADEs in patients attending general practice. This level of morbidity makes ADEs
      one of the most significant causes of morbidity in the Australian community.

PMID- 16584365
TI  - Glycaemic levels triggering intensification of therapy in type 2 diabetes in the
      community: the Fremantle Diabetes Study.
AB  - OBJECTIVE: To assess the effectiveness of the management of type 2 diabetes in an
      urban Australian setting. DESIGN AND SETTING: The Fremantle Diabetes Study (FDS),
      a community-based longitudinal observational study. PATIENTS: 531 FDS
      participants with type 2 diabetes, with mean age, 62.4 years (95% CI, 40.9-79.3
      years), 54% male, median diabetes duration 3.0 years (interquartile range [IQR],
      0.7-7.0 years), with valid data from the baseline FDS assessment and five
      subsequent annual reviews between 1993 and 2001. MAIN OUTCOME MEASURES: Glycated
      haemoglobin (HbA(1c)) levels at annual review visits before and after change in
      blood glucose-lowering therapy. RESULTS: Over 2893 patient-years of follow-up, 97
      patients (18%) progressed from dietary management to therapy with oral
      hypoglycaemic agents (OHA), and 45 (9%) progressed from OHA to insulin therapy,
      after a median duration of diabetes of 4.0 years (IQR, 2.9-5.5 years) and 8.1
      years (IQR, 5.5-13.0 years), respectively. Median HbA(1c) concentrations (IQR) at
      the review before OHA or insulin were started were 7.7% (6.9%-8.8%) and 9.4%
      (8.0%-10.7%), respectively. At the next annual review, HbA(1c) levels in the two
      groups had fallen to 7.4% (6.5%-8.1%) and 7.9% (7.2%-9.5%), respectively (P < or
      = 0.001). Intensification of therapy was associated with beneficial changes in
      serum lipid profiles, but not with an increase in frequency of hypoglycaemia.
      CONCLUSIONS: Most Australian patients with type 2 diabetes may be spending most
      of the duration of their disease with suboptimal glycaemic control (HbA(1c) >
      7.0%), despite the availability of a range of effective therapies, including
      insulin.

PMID- 16584366
TI  - A randomised controlled trial of hot water (45 degrees C) immersion versus ice
      packs for pain relief in bluebottle stings.
AB  - OBJECTIVE: To investigate the effectiveness of hot water immersion for the
      treatment of Physalia sp. (bluebottle or Portuguese Man-of-War) stings. DESIGN:
      Open-label, randomised comparison trial. Primary analysis was by intention to
      treat, with secondary analysis of nematocyst-confirmed stings. One halfway
      interim analysis was planned. SETTING: Surf lifesaving first aid facilities at
      two beaches in eastern Australia from 30 December 2003 to 5 March 2005.
      PARTICIPANTS: 96 subjects presenting after swimming in the ocean for treatment of
      an apparent sting by a bluebottle. INTERVENTIONS: Hot water immersion (45 degrees
      C) of the affected part versus ice pack application. MAIN OUTCOME MEASURES: The
      primary outcome was a clinically important reduction in pain as measured by the
      visual analogue scale (VAS). Secondary outcomes were the development of regional
      or radiating pain, frequency of systemic symptoms, and proportion with pruritus
      or rash on follow-up. RESULTS: 49 patients received hot water immersion and 47
      received ice packs. The two groups had similar baseline features, except patients
      treated with hot water had more severe initial pain (VAS [mean +/- SD]: 54 +/- 22
      mm versus 42 +/- 22 mm). After 10 minutes, 53% of the hot water group reported
      less pain versus 32% treated with ice (21%; 95% CI, 1%-39%; P = 0.039). After 20
      minutes, 87% of the hot water group reported less pain versus 33% treated with
      ice (54%; 95% CI, 35%-69%; P = 0.002). The trial was stopped after the halfway
      interim analysis because hot water immersion was shown to be effective (P =
      0.002). Hot water was more effective at 20 minutes in nematocyst-confirmed stings
      (95% versus 29%; P = 0.002). Radiating pain occurred less with hot water (10%
      versus 30%; P = 0.039). Systemic effects were uncommon in both groups.
      CONCLUSIONS: Immersion in water at 45 degrees C for 20 minutes is an effective
      and practical treatment for pain from bluebottle stings.

PMID- 16584367
TI  - After-hours discharges from intensive care are associated with increased
      mortality.
AB  - OBJECTIVE: To investigate the change in pattern of discharge of patients from an
      intensive care unit (ICU) to hospital wards and to determine the impact of
      discharge time on subsequent hospital mortality. DESIGN AND PARTICIPANTS: A
      retrospective cohort study of 10 903 patients discharged alive from a single ICU
      between 1 January 1992 and 31 December 2002. MAIN OUTCOME MEASURE: In-hospital
      mortality. RESULTS: Of the 10 903 patients discharged alive from the ICU, 486
      (4.5%) died in hospital wards. When discharge times were categorised according to
      nursing shift (morning, 07:00-14:59; afternoon, 15:00-21:59; and night, 22:00
      06:59), patients were more likely to be discharged on an afternoon shift (odds
      ratio, 3.63; 95% CI, 3.05-4.30) or night shift (4.52; 95% CI, 3.15-6.64) in 2000
      2002 compared with 1992-1994. In a multiple logistic model, hospital mortality
      after discharge from the ICU was increased by higher APACHE II score (1.14; 95%
      CI, 1.12-1.16); admission to ICU from the operating room (1.47; 95% CI, 1.11
      1.95) and from the general ward (1.75; 95% CI, 1.37-2.23); and discharge during
      the afternoon (1.36; 95% CI, 1.08-1.70) and night shifts (1.63; 95% CI, 1.03
      2.57). CONCLUSION: Over an 11-year period, more patients are being discharged
      from the ICU in the afternoon and night suggesting increasing pressure on ICU
      beds. Patients discharged on these shifts have an increased risk of death.

PMID- 16584368
TI  - Estimates of beneficial and harmful sun exposure times during the year for major
      Australian population centres.
AB  - OBJECTIVE: To examine the influence of geographical and seasonal factors on
      duration of solar ultraviolet (UV) radiation exposure of skin to produce
      recommended vitamin D levels without producing erythema. DESIGN AND SETTING: An
      ecological study using daily Ultraviolet Index (UVI) data collected in major
      population centres across Australia for 1 year (1 January - 31 December 2001) to
      calculate sun exposure times for recommended vitamin D production and erythema.
      MAIN OUTCOME MEASURES: Sun exposure times to produce either serum vitamin D
      concentrations equivalent to an oral intake of 200-600 IU/day or erythema for
      people aged 19-50 years with fair skin (Fitzpatrick type II skin) exposing 15% of
      the body. RESULTS: In January, across Australia, 2-14 minutes of sun three to
      four times per week at 12:00 is sufficient to ensure recommended vitamin D
      production in fair-skinned people with 15% of the body exposed. However, erythema
      can occur in as little as 8 minutes. By contrast, at 10:00 and 15:00, there is a
      greater difference between exposure time to produce erythema and that to produce
      recommended vitamin D levels, thereby reducing the risk of sunburn from
      overexposure. From October to March, around 10-15 minutes of sun exposure at
      around 10:00 or 15:00 three to four times per week should be enough for fair
      skinned people across Australia to produce recommended vitamin D levels. Longer
      exposure times are needed from April to September, particularly in southern
      regions of Australia. CONCLUSION: Our study reinforces the importance of existing
      sun protection messages for the summer months throughout Australia. However, fair
      skinned people should be able to obtain sufficient vitamin D from short periods
      of unprotected sun exposure of the face, arms and hands outside of the peak UV
      period (10:00-15:00) throughout Australia for most of the year. The greater
      variability in sun exposure times during winter, means that optimal sun exposure
      advice should be tailored to each location.

PMID- 16584370
TI  - Lack of integration of medical education in Australia: the need for change.
AB  - The lack of cohesion across health and education sections and national and state
      jurisdictions is counterproductive to effective national policies in medical
      education and training. Existing systems in Australia for medical education and
      training lack coordination, and are under resourced and under pressure. There is
      a need for a coordinated national approach to assessment of international medical
      graduates, and for meeting their education and training needs. The links between
      prevocational and vocational training must be improved. Tensions between
      workforce planning, education and training can only be resolved if workforce and
      training agencies work collaboratively. All prevocational positions should be
      designed and structured to ensure that service, training, teaching and research
      are appropriately balanced. There is a need for more health education research in
      Australia.

PMID- 16584369
TI  - COPDX: an update of guidelines for the management of chronic obstructive
      pulmonary disease with a review of recent evidence.
AB  - Long-acting beta(2) agonists are an effective and convenient treatment for
      chronic obstructive pulmonary disease (COPD), but do not significantly improve
      lung function. The long-acting anticholinergic tiotropium, which can be taken
      once daily, decreases exertional dyspnoea and increases endurance by reducing
      hyperinflation. The role in COPD of the combination of a long-acting beta(2)
      agonist and a glucocorticoid in a single inhaler remains unclear. The minimum
      duration of an effective pulmonary rehabilitation program that includes exercise
      training is 6 weeks. Long-term treatment with inhaled glucocorticoids may reduce
      the rate of decline in lung function, but the effect is small. Aminophylline
      should no longer be routinely used in acute exacerbations of COPD. Non-invasive
      positive pressure ventilation (NPPV) reduces mortality and hospital stay in
      patients with acute hypercapnic ventilatory failure; it is also an effective
      weaning strategy for patients who require intubation. Further studies are
      required to clarify the role of NPPV in the long-term management of stable COPD.

PMID- 16584371
TI  - Prevocational medical training in Australia: where does it need to go?
AB  - The workplace remains the most important learning environment for junior doctors
      in their postgraduate years. There is no national curriculum to guide the
      education of prevocational doctors. The apprenticeship model is under threat, and
      is not sustainable in the future without significant changes to the system.
      Supervision is crucial for junior doctors' learning and for safe, quality patient
      care.

PMID- 16584372
TI  - Amisulpride deliberate self-poisoning causing severe cardiac toxicity including
      QT prolongation and torsades de pointes.
AB  - Although clinical trials of the antipsychotic amisulpride revealed no cardiac
      adverse effects, four patients with severe cardiac toxicity after overdose were
      reported to Australian poisons information centres in 2004-2005. All four had QT
      prolongation over 500 ms, two had rate-dependent bundle branch block, two
      developed torsades de pointes, and one died after cardiac arrest. Pending further
      studies, we recommend electrocardiogram assessment until at least 16 h after
      amisulpride overdose and, if QT interval is prolonged, cardiac monitoring until
      the patient is clinically well and conduction intervals are normal.

PMID- 16584373
TI  - Missed conceptions: a call for "positive" family planning.

PMID- 16584374
TI  - Missed conceptions: the need for education.

PMID- 16584375
TI  - Spontaneous splenic rupture: a rare complication of Q fever in Australia.

PMID- 16584376
TI  - Prothrombinex use for the reversal of warfarin: is fresh frozen plasma needed?

PMID- 16584377
TI  - Establishment of an Australian motor neurone disease registry.

PMID- 16584378
TI  - Reversible obesity-related glomerulopathy following weight reduction.

PMID- 16584379
TI  - An integrated biological approach to nuclear receptor signaling in physiological
      control and disease.
AB  - The nuclear receptors (NRs)--vitamin D receptor (VDR); peroxisome proliferator
      activated receptor (PPAR) alpha, delta, gamma; and pregnane X receptor (PXR)--act
      as sensors for various molecules encountered by the body on a daily basis. The
      effects of these ligands can be understood by the fact that numerous genes
      involved in the cellular processes, such as general homeostasis, growth, and
      defense against microbes, are under the control of these five NRs. The target
      gene and protein expression patterns of VDR, PPARs, and PXR; the resulting
      changes in metabolite levels; and their physiological consequences create a
      network that can be monitored by high-throughput methods and analyzed by
      multimodal approaches, such as systems biology. We suggest that the fine
      regulation of this NR network is specific to each human individual and depends,
      in part, on the constellation of regulatory small nucleotide polymorphisms (SNPs)
      in his or her genome. When regulatory SNPs affect NRs response elements, lifetime
      exposure to food components will have different accumulative consequences on the
      expression of the respective NR target genes. These differences will influence
      the individual's susceptibility to aging-related diseases, such as type 2
      diabetes, atherosclerosis, cancer, and osteoporosis. Furthermore, it is
      anticipated that systems biology methods will also help to identify the most
      critical genes, proteins, or metabolites in the NR network that will serve as
      biomarkers for the early detection of these diseases.

PMID- 16584380
TI  - Silencing or knocking out eukaryotic gene expression by oligodeoxynucleotide
      decoys.
AB  - The elucidation of molecular and signaling pathways in eukaryotic cells is often
      achieved by targeting regulatory element(s) found in the promoter or the enhancer
      region of eukaryotic gene(s) using a double-stranded (ds) oligodeoxynucleotide
      (ODN) containing a specific cis-element. Our laboratory is focusing on dsODN
      decoys containing the TGF-beta element as a novel nonsteroidal antifibrotic for
      achieving normal wound healing. In the model systems discussed, there is either a
      specific gene possessing a specific cis-element or a cluster of genes with one
      gene containing the consensus cis-element. The rest of the genes in the cluster
      contain the cis-elements homologous to this consensus element, which allows for
      dsODN decoy regulation of a gene cluster at one time.

PMID- 16584381
TI  - RUNX expression and function in human B cells.
AB  - RUNX1 and RUNX3 are expressed at many stages of B-cell differentiation,
      suggesting that they play a role in the development and functions of this
      lineage. Transgenic mice lacking expression of RUNX1 or the RUNX protein-binding
      partner, CBFbeta, have defective B-cell development, with differentiation blocked
      at an early stage. Specific knockout of RUNX1 in adult hematopoietic cells also
      caused a decrease in the number of mature B cells, supporting a role for RUNX1 in
      both developmental and adult hematopoiesis. Furthermore, RUNX proteins have been
      shown to regulate several B-cell-specific genes and play an important role in TGF
      beta-induced immunoglobulin class switching to IgA. The importance of RUNX1 in B
      cell development is additionally demonstrated by its dysregulation in the
      t(12;21) translocation, which is the most frequent translocation found in acute
      lymphocytic leukemia. Epstein Barr virus immortalized human B lymphoblastoid cell
      lines express RUNX3, and cross-regulation of RUNX1 by RUNX3 occurs in these
      cells. Knockdown of RUNX3 in these cells induces RUNX1 expression and inhibits
      cell proliferation, directly showing that RUNX proteins can regulate B-cell
      growth.

PMID- 16584382
TI  - Biocompatible nanometal particle fluorescence enhancers.
AB  - Fluorometry has been used for more than a century to enhance the understanding of
      phenomena in molecular biology. With recent advances in light detection
      techniques, it is even more actively used in research now. The effectiveness of
      fluorometry highly depends on the intensity of the fluorescence from the target
      molecules in contrast to the background. Instrumentation for amplifying
      fluorescence signals may not selectively enhance signals only from the target.
      Therefore, a method to retrieve more fluorescence emission from a fluorophore is
      beneficial. Nanometal particles have high-density surface plasmon polariton
      fields, and when a fluorophore is placed within these fields, the electrons
      involved in the fluorescence emission may be altered in their energy states. The
      level of alteration depends upon the metal type, size of the particle, quantum
      yield of a fluorophore, and, most importantly, the distance between the
      nanoparticle and the fluorophore. Some organic solvents are also found to enhance
      fluorescence, possibly by the dipole-dipole coupling between the fluorophore and
      the solvent, resulting in an increase in the energy gap between the excited and
      the ground states. In this article, study results of the application of nanometal
      particles and biocompatible solvents for increasing the sensitivity/resolution in
      fluorophore-mediated biosensing/bioimaging are reviewed.

PMID- 16584383
TI  - PET-based biological imaging for radiation therapy treatment planning.
AB  - Biologically conformal radiation therapy (BCRT), a convergence of intensity
      modulated radiation therapy (IMRT) and positron emission tomography (PET)-based
      functional imaging, incorporates patient-specific, image-derived biological
      information. This approach may potentially lead to a paradigm shift in radiation
      therapyspatially varying dose prescriptions, or dose sculpting, for
      individualized and dosimetrically optimized treatment. This article reviews the
      current status of the technical, biological, and clinical aspects of PET-guided
      radiation therapy. It remains unclear, however, whether PET is currently capable
      of delineating the true extent of viable tumor with sufficient accuracy and
      precision to reliably guide therapy on a routine basis.

PMID- 16584385
TI  - Intravenous hydration with a 2.5% glucose solution in Type II diabetes.
AB  - Physicians are often unclear about how fast intravenous glucose solutions should
      be administered to adequately hydrate patients with Type II diabetes while
      avoiding hyperglycaemia and excessive plasma volume expansion. The aim of the
      present study was to analyse the disposition of a 2.5% glucose solution and
      create a nomogram which could serve as a guide to fluid therapy in these
      patients. Twelve males (mean body mass index, 29 kg/m(2)) with Type II diabetes
      due to insulin resistance, as quantified by an euglycaemic hyperinsulinaemic
      glucose clamp, received an infusion of iso-osmotic 2.5% glucose solution with
      electrolytes (70 mmol/l sodium, 45 mmol/l chloride and 25 mmol/l acetate) at
      individual rates over 30 and 60 min respectively. Blood glucose and haemoglobin
      levels were measured repeatedly over 3.5 h to estimate the kinetics of glucose
      and fluid volume. Mean insulin sensitivity was 4.2x10(-4) dlxkg(-1)xmin(
      1)x(micro-units/ml)(-1). The individualized infusion rates reached the
      predetermined blood glucose level of 12 mmol/l with a mean difference of 0.2
      mmol/l. The disposition of glucose was an important factor governing fluid
      distribution. The volume of distribution of exogenous glucose averaged 19.8
      litres, but for the fluid volume it was only 3.7 litres. The clearance was 0.37
      litre/min for glucose and 0.10 litre/min for the fluid volume, and the results of
      the 30-min and 60-min infusions agreed reasonably well. It is concluded that
      kinetic analysis can be used to guide the infusion time and infusion rate of 2.5%
      glucose to reach any predetermined glucose level and volume expansion.

PMID- 16584384
TI  - Signalling cross-talk between hepatocyte nuclear factor 4alpha and growth-hormone
      activated STAT5b.
AB  - In the present study, we have characterized signalling cross-talk between STAT5b
      (signal transducer and activator of transcription 5b) and HNF4alpha (hepatocyte
      nuclear factor 4alpha), two major regulators of sex-dependent gene expression in
      the liver. In a HepG2 liver cell model, HNF4alpha strongly inhibited beta-casein
      and ntcp (Na+/taurocholate cotransporting polypeptide) promoter activity
      stimulated by GH (growth hormone)-activated STAT5b, but had no effect on
      interferon-gamma-stimulated STAT1 transcriptional activity. By contrast, STAT5b
      synergistically enhanced the transcriptional activity of HNF4alpha towards the
      ApoCIII (apolipoprotein CIII) promoter. The inhibitory effect of HNF4alpha on
      STAT5b transcription was associated with the inhibition of GH-stimulated STAT5b
      tyrosine phosphorylation and nuclear translocation. The short-chain fatty acid,
      butyrate, reversed STAT5b transcriptional inhibition by HNF4alpha, but did not
      reverse the inhibition of STAT5b tyrosine phosphorylation. HNF4alpha inhibition
      of STAT5b tyrosine phosphorylation was not reversed by pervanadate or by dominant
      negative phosphotyrosine phosphatase 1B, suggesting that it does not result from
      an increase in STAT5b dephosphorylation. Rather, HNF4alpha blocked GH-stimulated
      tyrosine phosphorylation of JAK2 (Janus kinase 2), a STAT5b tyrosine kinase. Thus
      STAT5b and HNF4alpha exhibit bi-directional cross-talk that may augment HNF4alpha
      dependent gene transcription while inhibiting STAT5b transcriptional activity via
      the inhibitory effects of HNF4alpha on JAK2 phosphorylation, which leads to
      inhibition of STAT5b signalling initiated by the GH receptor at the cell surface.

PMID- 16584386
TI  - Expression of the Blomia tropicalis paramyosin Blo t 11 and its immunodominant
      peptide in insect cells.
AB  - Blo t 11, a dust-mite (Blomia tropicalis) paramyosin, is an allergen with
      significant IgE reactivity that has potential as a diagnostic/therapeutic reagent
      for house-dust-mite allergy. The present study describes the successful
      expression of Blo t 11 and its immunodominant peptide fD in insect cells using a
      baculovirus expression system. The Blo t 11 and fD genes were cloned into the
      pMelBacA vector and the resulting vectors were co-transfected into Sf9 insect
      cells with Bac-N-Blue DNA. Plaque assay was used to select for recombinant virus
      that was then used to infect High Five insect cells for protein expression.
      Secreted proteins were harvested by immuno-affinity purification using monoclonal
      antibodies to Blo t 11. Purified proteins were analysed by immunoblotting, N
      terminal sequencing and ELISA. Immunoblot analyses revealed the full-length Blo t
      11 cDNA expressed as a minor protein band of approx. 200 kDa and two major
      protein bands of approx. 60 and 70 kDa. Clones expressing fD cDNA fragment
      produced a protein of approx. 30 kDa that was confirmed to be fD by N-terminal
      sequencing. Approx. 4-7.5 mg/l of fD and 1 mg/l of Blo t 11 were obtained by
      affinity purification. ELISA results showed that human IgE reactivity to these
      recombinant allergens was lower as compared with that of the native Blo t 11,
      suggesting that these baculovirus-expressed allergens exhibiting reduced
      allergenicity could be useful for the development of immunotherapeutic reagents
      for mite allergy.

PMID- 16584387
TI  - Non-invasive diagnosis of large oesophageal varices with FibroTest in patients
      with cirrhosis: a preliminary retrospective study.
AB  - BACKGROUND AND AIMS: Primary prevention of variceal bleeding with beta-blockers
      improves survival in patients with large oesophageal varices (LOV). Therefore,
      cirrhotic patients frequently undergo screening endoscopy. As portal hypertension
      is related to liver fibrosis, this study aimed to assess the predictive value of
      FibroTest, a non-invasive marker of liver fibrosis, for the diagnosis of LOV in
      cirrhotic patients. METHODS: Ninety-nine cirrhotic patients had clinical
      examination, blood sample (liver function tests, platelet count, FibroTest) and
      upper endoscopy. Measurements of endoscopic and biochemical parameters were made
      blindly. Sensitivity, specificity, predictive values and area under the receiver
      operating characteristic curves were assessed for FibroTest, platelet count and
      Child-Pugh score. The main endpoint was the presence of LOV. RESULTS: Platelet
      count, prothrombin time, ascites, FibroTest and Child-Pugh class were
      significantly different among patients with or without LOV. FibroTest had the
      highest discriminative power with an area under receiver operating
      characteristics curves of 0.77 (SE=0.06), compared with 0.64 (0.08) and 0.68
      (0.08) for platelet count and Child-Pugh score, respectively (P=0.08). A cut-off
      at 0.80 had a 86% negative predictive value for the diagnosis of LOV (Se=92%,
      Sp=21%). CONCLUSION: FibroTest could aid in the diagnosis of LOV and may
      therefore reduce the indication of endoscopic screening in cirrhotic patients.

PMID- 16584388
TI  - Role of CYP2D6 polymorphism in predicting liver fibrosis progression rate in
      Caucasian patients with chronic hepatitis C.
AB  - OBJECTIVE: Previous studies have demonstrated that CYP2D6 polymorphism is
      associated with liver cirrhosis. The aim of the present study was to find out
      whether CYP2D6*4, the poor metabolizer allele can predict fibrosis progression
      rate. METHODS: Seventy-five Caucasian patients with chronic hepatitis C infection
      were recruited. They were divided into two groups, 'fast fibrosers' and 'slow
      fibrosers', according to Poynard's fibrosis progression curves. Sixty-two
      patients underwent liver biopsy. Twenty healthy neonates were included as control
      population. DNA was extracted from peripheral blood and CYP2D6*4 was tested by
      polymer chain reaction using fluorescent hybridization probes in a lightCycler
      instrument. RESULTS: Forty-two patients were classified as 'fast fibrosers' and
      33 patients as 'slow fibrosers'. The frequency of CYP2D6*4 allele in the 'fast
      fibrosers' (34.5%) was significantly higher compared with the 'slow fibrosers'
      (15%) (P-value=0.007). There was no significant difference between the frequency
      of CYP2D6*4 in the 'slow fibrosers' (15%) compared with the controls (12.5%).
      Carrier state of CYP2D6*4 was the only covariate that was significantly
      positively correlated with fast progression to cirrhosis (odds ratio=6.5,
      P=0.01). CONCLUSION: This study indicates for the first time that CYP2D6 genotype
      might be a significant predictor of liver fibrosis progression rate in chronic
      hepatitis C patients.

PMID- 16584389
TI  - Multidrug resistance 1 genotype and disposition of budesonide in early primary
      biliary cirrhosis.
AB  - BACKGROUND: Budesonide, which is a dual substrate of P-glycoprotein, the product
      of the multidrug resistance 1 (MDR1) gene, and cytochrome P450 3A (CYP3A) has
      been proposed for treatment of early primary biliary cirrhosis (PBC). Recently,
      MDR1 gene polymorphisms have been discussed as a potential cause of
      glucocorticoid resistance. We tested the hypothesis that MDR1 gene polymorphisms
      affect absorption of oral budesonide. METHODS: In 21 patients with histologically
      proven early-stage (I/II) PBC and nine healthy subjects, we evaluated the impact
      of MDR1 single nucleotide polymorphisms (2,677G>T,A and 3,435C>T) on disposition
      of a single oral dose of 3 mg budesonide. CYP3A5 gene polymorphisms (6,986A>G)
      were analyzed in parallel. RESULTS: In MDR1 2,677 GG and 3,435 CC genotypes,
      absorption and elimination of budesonide were not significantly different from
      those in corresponding homozygous variants. Peak plasma levels and areas under
      the plasma concentration time curves (AUC) of budesonide were not lower in MDR1
      3,435 CC with putatively high intestinal expression of P-glycoprotein than in
      MDR1 3,435 TT. Interestingly, in two CYP3A5*1/*3 carriers with high enzyme
      activity, lower AUC was noted than in 28 CYP3A5*3/*3 carriers with a deficient
      enzyme. CONCLUSION: Common MDR1 gene polymorphisms do not affect disposition of
      budesonide in early PBC.

PMID- 16584390
TI  - The development and clinical features of splenic aneurysm associated with liver
      cirrhosis.
AB  - OBJECTIVES: Splenic artery aneurysm (SAA) is usually asymptomatic, but can be
      fatal if it ruptures. Portal hypertensive patients with varix or splenomegaly are
      sometimes complicated by SAA. However, there have been no large-scale clinical
      studies regarding whether liver cirrhosis itself is associated with splenic
      aneurysm regardless of varix or splenomegaly. METHODS: In the present study, we
      retrospectively analyzed 303 cirrhotic patients examined with arteriography. The
      diagnosis and characteristics of SAAs were determined, and the relation with
      splenic artery diameter was evaluated. RESULTS: Nine patients (2.97%) had 12
      complicated SAAs. The aneurysms, which measured 4-22 mm in diameter, were all
      saccular, and occurred commonly in the splenic hilum (50.0%). A correlation was
      noted between splenic artery diameter and aneurysm diameter (R(2)=0.706).
      Aneurysm growth was strongly associated with an increase in diameter of the
      splenic artery trunk (R(2)=0.705), which is closely related to arterial flow.
      CONCLUSIONS: SAA is considered a complication of cirrhosis. The increase in
      splenic artery diameter may result in SAA enlargement and rupture. Elective
      procedures should be considered based on the follow-up of main trunk or diameter
      of the splenic artery in addition to SAA size, a known risk factor of aneurysmal
      rupture.

PMID- 16584391
TI  - The effect of the metabolic syndrome, hepatic steatosis and steatohepatitis on
      liver fibrosis in hereditary hemochromatosis.
AB  - OBJECTIVES: The variability in phenotypic expression of hereditary
      hemochromatosis (HH) is not fully understood. We sought to examine whether the
      metabolic syndrome, hepatic steatosis or steatohepatitis influenced hepatic
      fibrosis among patients with HH and iron overload. METHODS: We identified 86
      patients with C282Y/C282Y or C282Y/H63D HH and iron overload (hepatic iron
      concentration (HIC) >2,200 microg/g for males, >1,600 microg/g for females).
      Features of the metabolic syndrome were assessed at the time of liver biopsy.
      Biopsies were scored by a blinded pathologist. Significant fibrosis was defined
      as peri-portal fibrosis or greater. RESULTS: The mean (+/-SD) age of the study
      population was 53+/-12 years and 68 (79%) were male. The median (range) values of
      ferritin and HIC were 1,125 (253-9,530) microg/l and 9963 (1926-50 887) microg/g,
      respectively. The metabolic syndrome was present in 23 (27%), hepatic steatosis
      in 43 (50%), steatohepatitis in 18 (21%) and significant fibrosis in 38 (44%).
      Overall, neither the metabolic syndrome nor any of its components were associated
      with significant fibrosis or a higher mean fibrosis stage. Hepatic steatosis but
      not steatohepatitis was associated with a lower fibrosis stage. C282Y/H63D
      compound heterozygous individuals who had glucose intolerance had more severe
      fibrosis compared with those without glucose intolerance (1.0+/-1.0 vs. 0.1+/
      0.3, P=0.01). CONCLUSIONS: Overall, the metabolic syndrome and fatty liver were
      not associated with hepatic fibrosis among individuals with HH and iron overload.
      However, glucose intolerance may be important risk factor for the development of
      hepatic fibrosis in subjects with the C282Y/H63D HFE genotype.

PMID- 16584392
TI  - Efficacy and tolerance of interferon-alpha in the treatment of chronic hepatitis
      C in end-stage renal disease patients on hemodialysis.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) show a high prevalence
      of hepatitis C, with a negative impact on the survival on hemodialysis and after
      renal transplantation. We evaluated the efficacy and tolerance of interferon
      alpha (IFN-alpha) in HCV-infected ESRD patients on dialysis. METHODS: Forty-six
      HCV-RNA-positive ESRD patients were studied. IFN-alpha regimen consisted of 3
      million units three times a week for 12 months, and the patients were followed up
      for 6 months. End-of-treatment, and sustained biochemical and virological
      responses were evaluated and tolerance was assessed monthly. RESULTS: A sustained
      virological response (SVR) was observed in 10/46 patients (22%) and in 10/29 who
      completed the treatment (34%). Alanine aminotransferase was elevated in 63% of
      the patients at the beginning of the study and returned to normal levels within
      the first month in all patients with SVR. Treatment was discontinued because of
      side effects in 11/46 patients (24%) and six patients (13%) were lost to follow
      up. CONCLUSIONS: IFN-alpha monotherapy for hepatitis C in dialysis patients shows
      a high frequency of adverse effects. However, the SVR is high (34%) in patients
      who complete treatment, emphasizing the importance of careful selection and close
      follow-up in order to minimize and control possible side effects.

PMID- 16584393
TI  - Circulating level of large splice variants of tenascin-C is a marker of piecemeal
      necrosis activity in patients with chronic hepatitis C.
AB  - BACKGROUND: It has been reported that histological activity index and piecemeal
      necrosis are good factors to evaluate the prognosis in patients with chronic
      hepatitis C (CHC). Thus, there is a need for simple and noninvasive means to
      assess disease activity and piecemeal necrosis in patients with CHC. In this
      study, we measured the serum concentrations of large splice variants of tenascin
      C (cTN-C) in patients with CHC, and examined their correlation with the degree of
      inflammatory activity and fibrosis as evaluated in liver biopsy specimens.
      METHODS: The serum levels of cTN-C in 150 patients with CHC and 50 healthy
      volunteers were measured by enzyme-linked immunosorbent. The histology of liver
      biopsy specimens was also evaluated following the Desmet's grading/staging system
      and the Ishak's classification. Liver specimens obtained by biopsy were also
      immunohistochemically evaluated with anti-human tenascin-C antibodies. RESULTS:
      Serum cTN-C concentrations were significantly higher in CHC patients than in
      healthy volunteers (P < 0.0001). The levels of cTN-C showed no significant
      difference among the fibrosis stages as assessed by the Desmet's grading/staging
      system and Ishak's classification scores. However, the concentration of cTN-C was
      significantly correlated with the grade of activity. According to the Ishak's
      classification, the concentration of cTN-C was increased in proportion to the
      degree of piecemeal necrosis. Specific immunostaining of cTN-C was observed in
      limited areas of piecemeal necrosis but not in fibrotic areas. CONCLUSION: The
      measurement of serum levels of cTN-C is a useful marker of the activity of CHC,
      in particular of the degree of piecemeal necrosis.

PMID- 16584394
TI  - Consensus interferon and ribavirin for patients with chronic hepatitis C and
      failure of previous interferon-alpha therapy.
AB  - BACKGROUND: The efficacy of consensus interferon (CIFN), a synthetic IFN with
      optimised in vitro activity, was assessed in chronic hepatitis C virus (HCV)
      patients who had failed the pretreatment with interferon-alpha (IFNalpha) and
      ribavirin. METHODS: One hundred and three patients after non-response (n=69) or
      relapse (n=34) to IFNalpha+/-ribavirin were randomly assigned to high-dose
      induction (CIFN 27-->9 microg daily for 24 weeks, 9 microg t.i.w. for 24 weeks)
      or low-dose treatment (CIFN 18 microg t.i.w. for 12 weeks, 9 microg t.i.w. for 36
      weeks); each with ribavirin 800 mg/day. Follow-up was 24 weeks. RESULTS: Non
      responder patients treated with high-dose induction had higher early virological
      response rates (63% vs. 39%, P<0.05). This initial positive effect was lost
      during the last 24 weeks of treatment yielding sustained virological response
      (SVR) rates of 26% in both groups. Relapse patients revealed SVR in 70% and 38%
      in groups A and B (NS). Treatment was well tolerated with side effect-related
      preterm discontinuations in 8% and 5%. CONCLUSIONS: CIFN and ribavirin treatment
      induced considerable SVR rates in patients with non-response or relapse to
      IFNalpha+/-ribavirin. Viral elimination rates might be further increased by
      continuous daily administration of CIFN and weight-adjusted ribavirin dosing.

PMID- 16584395
TI  - Interleukin-10 promoter polymorphisms are associated with the mode and sequel of
      HBeAg seroconversion in patients with chronic hepatitis B virus infection.
AB  - BACKGROUND: The influence of interleukin-10 (IL-10) gene promoter polymorphisms
      on the mode and sequel of HBeAg seroconversion (a favorable event usually) in
      patients with chronic Hepatitis B virus (HBV) infection has not been clarified.
      PATIENTS AND METHODS: IL-10 genotyping and haplotype analyses of 340 HBsAg
      carriers and 100 volunteers with self-limiting HBV infection from southern China,
      a high prevalent area of HBV were performed according to the single nucleotide
      polymorphisms in its promoter (-1,082, -819 and -592) using a competitively
      differentiated PCR. RESULTS: High-producer genotype (GG at -1,082) or haplotype
      (GCC) was rarely found in patients from southern China (<1%). Intermediate
      producer haplotype (ACC) was closely associated with chronic liver disease
      (P=0.004); compared with this, low-producer genotype (AA at -592) and haplotype
      (ATA) were closely associated with asymptomatic carriers (P=0.035 and 0.035).
      Intermediate-producer genotype (AC at -592) and haplotype (ACC) were closely
      associated with covert seroconversion of HBeAg (P=0.0086 and 0.0013) and
      progressive sequel after HBeAg seroconversion (P=0.013 and 0.0008), while, low
      producer genotype (AA at -592) and haplotype (ATA) were closely associated with
      overt seroconversion of HBeAg (P=0.0023 and 0.0061) and silent sequel after HBeAg
      seroconversion (P=0.0009 and 0.001). CONCLUSIONS: IL-10 gene promoter
      polymorphisms significantly influence the mode and sequel of HBeAg seroconversion
      in patients with chronic HBV infection.

PMID- 16584396
TI  - Hepatic cavernous hemangioma: underrecognized associated histologic features.
AB  - BACKGROUND/AIMS: Cavernous hemangiomas (CH) are typically described as solitary,
      well-circumscribed lesions and are reported to have a distinct fibrous interface.
      This study describes underrecognized histological changes of large hepatic
      hemangiomas that contradict this long-standing view. METHODS: Nineteen cases of
      hepatic resections for CH were reviewed. Stains for estrogen and progesterone
      receptors (ER/PR), MIB-1, alpha-smooth muscle actin, collagen IV, and elastic Van
      Gieson stains were applied to the lesions. RESULTS: The CHs measured 5-31 cm
      (mean 16.6 cm). Sixteen (84%) CHs had an irregular interface with the liver
      parenchyma while only three had the well-defined fibrous capsule typically
      described for CH. Fifteen (79%) CHs had dilated vascular spaces filled with blood
      0.1-2.0 cm beyond the confines of the main CH, which we have designated
      hemangioma-like vessels (HLVs). The histochemical and immunohistochemical stains
      in both CH and HLVs were similar, with the walls of the vessels composed
      predominantly of collagen with some faint elastic fibers and smooth muscle,
      endothelium underlined by collagen IV, negative ER/PR in all components, and a
      proliferation rate of <5/100 endothelial cells. CONCLUSION: Irregular edges of CH
      and HLVs in the liver parenchyma adjacent to CH have been underrecognized. No
      significant differences in staining or proliferative rate were present between
      CHs and HLVs, suggesting the HLVs are within the spectrum of CH.

PMID- 16584397
TI  - Selective elimination of hepatic natural killer T cells with concanavalin A
      improves liver regeneration in mice.
AB  - BACKGROUND: Although concanavalin A (Con A) as a T cell stimulant can cause
      natural killer T (NKT) cell-mediated liver injury in mice and a nonhepatotoxic
      dose of Con A can trigger innate immune cells including NKT cells to prevent
      tumor metastasis in the liver, little is known about the role of Con A-primed NKT
      cells in liver repair. In this study, we aimed to investigate the effect of
      pretreatment with a nontoxic dose of Con A on subsequent liver regeneration in
      mice. METHODS: A nontoxic dose of Con A was injected intravenously 24 h before
      partial hepatectomy (PHx), which was used as a model of liver regeneration.
      Ratios of remnant liver mass to body weight, bromodeoxyuridine (BrdU)
      incorporation and proliferating cell nuclear antigen (PCNA) labeling were used to
      assess liver regeneration. RESULTS: Hepatic mononuclear cells were isolated and
      analyzed by flow cytometry. After PHx, the ratios of liver weight to body weight,
      PCNA-positive hepatocytes and BrdU-positive hepatocytes in Con A-pretreated mice
      were significantly higher than that of phosphate-buffered saline-treated mice,
      indicating that Con A pretreatment can accelerate liver regeneration. Flow
      cytometric analysis showed that NKT cells were significantly activated and
      selectively eliminated after the Con A administration. Moreover, NKT cells
      expressed more apoptosis-related molecules, Fas and Annexin V. CONCLUSIONS: Taken
      together, Con A accelerates liver regeneration in mice by eliminating hepatic NKT
      cells via activation-induced cell death.

PMID- 16584398
TI  - Lack of macrophage migration inhibitory factor protects mice against concanavalin
      A-induced liver injury.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is involved in
      inflammatory and immune-mediated diseases but the role of MIF in liver injury has
      not yet been elucidated. METHODS: We investigated biochemically, histologically
      and immunologically the character of MIF in concanavalin A (Con A)-induced T-cell
      mediated liver injury using MIF knockout (KO) mice and wild-type (WT) mice.
      RESULTS: MIF KO mice showed significantly decreased serum alanine
      aminotransferase values and suppressed histological change with massive necrosis
      of the hepatic parenchymal cells and infiltration of inflammatory cells compared
      with their WT counterparts. This protection was not mediated by either tumor
      necrosis factor-alpha or interferon-gamma, which are critical mediators of Con A
      induced liver injury, as their serum concentrations were shown to be similar in
      MIF KO and WT mice. On the other hand, a flow cytometric analysis demonstrated
      that the number of activated hepatic leukocytes decreased more in the MIF KO mice
      than in the WT mice. CONCLUSIONS: A lack of MIF protected the mice from Con A
      induced liver injury. Controlling the MIF activity may be a useful therapeutic
      strategy for treating such T-cell activation-associated liver diseases as
      autoimmune hepatitis and viral hepatitis.

PMID- 16584399
TI  - Effect of serotonin receptor 2 blockage on liver regeneration after partial
      hepatectomy in the rat liver.
AB  - The effect of serotonin receptor 2 blockade (5-HT(2)) on liver regeneration after
      30-34% and 60-70% partial hepatectomy in the rat liver was investigated.
      MATERIALS AND METHODS: Male Wistar rats were subjected to 60-70% (group I) and 30
      34% (group II) partial hepatectomy. Serotonin receptor 2 blockade was exerted by
      intraperitoneal administration of ketanserin at different doses and time points
      after partial hepatectomy. The rats of all groups were killed at different time
      points until 96 h after partial hepatectomy. The rate of liver regeneration was
      evaluated by the mitotic index in hematoxylin and eosin sections, the
      immunochemical detection of Ki67 and proliferating cell nuclear antigens, the
      rate of [(3)H]-thymidine incorporation into hepatic DNA and liver thymidine
      kinase enzymatic activity. RESULTS: Liver regeneration peaked at 24 and 32 h
      after partial hepatectomy in 60-70% hepatectomized rats. In 30-34% hepatectomized
      rats liver regeneration peaked at 60 h, whereas low rates of regenerative
      activity were observed between 24 and 72 h after partial hepatectomy. Ketanserin
      administration arrested liver regeneration only when administered at 16 h after
      60-70% partial hepatectomy. Ketanserin also abrogated the observed peak of
      regenerative activity at 60 h in 30-34% hepatectomized rats when administered at
      52 h after partial hepatectomy. All indices of liver regeneration were affected
      by ketanserin administration. CONCLUSIONS: Serotonin receptor 2 blockade can
      arrest liver regeneration only when administered close to G1/S transition point,
      and that while serotonin may be a cofactor for DNA synthesis, it does not play a
      role in initiation of liver regeneration.

PMID- 16584400
TI  - Multidrug resistance associated protein 2 mediates transport of prostaglandin E2.
AB  - BACKGROUND/AIM: Inactivation of prostaglandin E(2) (PGE(2)) in the liver is a
      rapid process and occurs mainly through beta-oxidation in the peroxisome of the
      hepatocyte. Biliary excretion of PGE(2) is also a means of elimination from the
      liver. We investigated the role of multidrug resistance-associated protein 2
      (MRP2) in the transport of PGE(2). METHODS: Biliary PGE(2) elimination was
      measured in liver perfusions in Wistar and MRP2-deficient TR(-) rats.
      Furthermore, transport experiments were performed in membrane vesicles from human
      MRP2-infected Spodoptera frugiperda 21 (Sf21) insect cells. RESULTS: The liver
      perfusions showed a 3.5 times higher percentage of undegraded [(3)H]PGE(2) in
      bile of Wistar rats in comparison with MRP2 deficient (TR(-)) rats (3.6% vs.
      1.1%, respectively; P<0.05). MRP2-mediated transport of the model substrate
      [(3)H]DNP-SG was inhibited by PGE(2). Half maximal inhibition was achieved at a
      concentration of approximately 15 microM PGE(2). In addition, [(3)H]PGE(2) uptake
      in these vesicles was detected, and determined to be ATP dependent. CONCLUSION:
      MRP2 mediates the transport of PGE(2) and its breakdown products. The biliary
      excretion of PGE(2) via MRP2 may contribute to rapid elimination of the
      prostaglandin but might also serve to relay prostaglandin signalling to the
      biliary tree.

PMID- 16584401
TI  - Patient-derived dendritic cells transduced with an a-fetoprotein-encoding
      adenovirus and co-cultured with autologous cytokine-induced lymphocytes induce a
      specific and strong immune response against hepatocellular carcinoma cells.
AB  - BACKGROUND/AIMS: Breaking immunologic tolerance towards the hepatocellular
      carcinoma (HCC)-associated alpha-fetoprotein (AFP) antigen is possible. The use
      of this potential for the treatment of immunocompromised HCC patients is limited.
      In this study, we analyzed whether dendritic cells (DCs) from HCC patients
      transduced with a human AFP (hAFP)-expressing adenovirus and co-cultured with
      cytokine-induced killer (CIK) cells can induce a strong specific immune response
      against HCC-cells. METHODS: An hAFP-encoding adenovirus (Ad-hAFP) was generated.
      DCs from healthy donors or patients were transduced at a very high efficacy.
      Afterwards, DCs were co-cultured with autologous CIK-cells, and their ability to
      lyse HCC-cells was analyzed. RESULTS: AFP-transduced DCs stimulated CIK cells
      strongly to lyse about 70% of AFP-expressing HCC cells. Cytotoxicity was
      significantly higher when lymphocytes were co-cultured with Ad-hAFP-transduced
      DCs than with Ad-mock-transduced DCs, indicating an AFP-specific immune response.
      More interestingly, CIK cells from patients with AFP-positive HCC could be
      stimulated to lyse AFP-expressing HCC cells as effectively as CIK cells from
      healthy individuals and stronger than CIK cells from patients without AFP
      expressing HCC. CONCLUSIONS: The data demonstrate that patient-derived DCs that
      were transduced with an AFP-expressing adenovirus and co-cultured with autologous
      CIK cells induce an AFP-specific, strong immune response against HCC cells.
      Therefore, this approach may have a potential for an adoptive and/or DC-based
      immunotherapy for HCC patients.

PMID- 16584402
TI  - Matrix metalloproteinase, hepatocyte growth factor, and tissue inhibitor of
      matrix metalloproteinase during human liver regeneration.

PMID- 16584403
TI  - Multiple intrahepatic implantations of hepatocellular carcinoma following
      percutaneous ethanol injection (PEI) therapy.

PMID- 16584404
TI  - RCAS1-expressing macrophages in inflammatory liver diseases.

PMID- 16584406
TI  - Psychological impact on implant patients' oral health-related quality of life.
AB  - OBJECTIVES: The literature has shown that patients' satisfaction with dental
      prostheses is associated with the existence of certain personality profiles. It
      is important to study such relationships in dental implant patients. MATERIAL AND
      METHODS: Fifty patients (28 men and 22 women), aged between 22 and 71 years (mean
      age 43.22 years, SD 12.24 years), who were partially edentulous and were seeking
      dental implant therapy were entered into this study. The patients were requested
      to answer two reliable and valid questionnaires--the Dental Impact on Daily
      Living (DIDL) and the Neuroticism Extraversion Openness Five-Factor Inventory
      (NEO-FFI)--before implant treatment and 2-3 months after prosthodontic
      rehabilitation therapy. RESULTS: Certain personality traits were found to have a
      significant relationship with patients' satisfaction with dental implants both
      before and after implant therapy (P < 0.05). Neuroticism score had valuable
      features in predicting patients' total satisfaction ratings (P = 0), satisfaction
      with appearance dimension (P = 0), satisfaction with oral comfort dimension (P =
      0.005) as well as satisfaction with general performance dimension (P = 0).
      CONCLUSION: Personality traits have an impact on patients' satisfaction with
      dental implant therapy. In addition, personality traits provide valuable
      information for the prediction of patients' satisfaction with their implant
      supported prostheses. Neuroticism, openness, agreeableness and consciousness are
      very helpful in this regard. Neuroticism was found the main predictor of the
      patients' oral health-related quality of life following implant treatment.

PMID- 16584407
TI  - Structural and radiological parameters for the characterization of jawbone.
AB  - OBJECTIVES: The aim of this study was to determine the Hounsfield values of
      selected bone sites on a computed tomography (CT) scan of the jaw and to
      investigate the relationship between this radiological parameter and structural
      parameters. MATERIALS AND METHODS: A selection of 24 bone samples out of eight
      cadaver human jaws was made. The following parameters were measured: Hounsfield
      value in the jaw (HU1) determined by a first CT scan, Hounsfield value of the
      excised bone specimen (HU2) by a second CT scan, bone mineral density (BMD) by a
      dual-energy X-ray absorptiometry scan, bone volume (BV/TV) by the microfocus CT
      scan, first peak transmission time (T(US-1)) and first zero crossing transmission
      time (T(US-2)) by an ultrasound measurement and Young's modulus (E(MECH)) by a
      compression test. RESULTS: Thirteen specimens were composed of a mix of
      trabecular and a small amount of cortical bone, while another 11 specimens were
      composed of trabecular bone only. A good correlation was found between the HU
      value of the specimen (HU2) and BMD (rho = 0.99), BV/TV (rho = 0.97), T(US-1)
      (rho = -0.83), T(US-2) (rho = -0.87) and E(MECH) (rho = 0.83). For the pure
      trabecular bone specimens, the HU value of the excised bone specimen (HU2) was
      highly correlated (rho = 0.95) with the HU value of the total jaw scan (HU1). For
      mixed trabecular-cortical bone specimens, this relationship was weak (rho =
      0.57). CONCLUSION: With the current CT scan technology, predictions of the
      mechanical properties of trabecular jaw bone based on Hounsfield values were only
      valid for jaws with a thin layer of cortical bone. For jaws with a thicker
      cortical layer, the prediction of the mechanical properties decreased
      significantly.

PMID- 16584408
TI  - Radiographic assessment of bone density around integrated titanium implants after
      ovariectomy in rats.
AB  - OBJECTIVES: This study evaluated the influence of ovariectomy 8 weeks after
      implant placement on bone integrated to titanium implants. MATERIAL AND METHODS:
      Thirty-eight female rats were submitted to a titanium implant at the tibiae
      proximal methaphysis. After a healing period of 8 weeks the animals were randomly
      divided into three groups: control (CTL-10 animals), sham-operated (SHAM-14
      animals) and ovariectomy (OVX-14 animals). The CTL group was then sacrificed in
      order to confirm integration of the implant. The SHAM group was submitted to
      fictitious surgery and the OVX group was submitted to bilateral ovariectomy.
      After 12 weeks post-implant placement, the SHAM and OVX groups were sacrificed.
      In order to confirm the systemic osteopenia in rats, a dual-energy X-ray
      absorptiometry (DXA) was performed. For the evaluation of bone density, digital
      radiographs were taken. The grey level of the bone adjacent to implant was
      measured using image software and the bone density was calculated at six points
      on both sides of the implant. RESULTS: Densitometry measurements of the femur
      confirmed systemic bone mass loss in the OVX group. Individualized bone analyses
      of different regions surrounding the implant showed a significantly lower
      radiographic bone density (P < 0.05) in the cancellous region of the OVX group
      (77.48 +/- 23.39 grey levels) when compared with the CTL and SHAM groups (91.61
      +/- 32.10 and 102.57 +/- 32.50 grey levels, respectively). CONCLUSIONS: The
      present study showed a decrease of the radiographic bone density in the
      cancellous region of bone around titanium implants placed 8 weeks before
      ovariectomy in rats.

PMID- 16584409
TI  - Clinical and radiographic evaluation of small-diameter (3.3-mm) implants followed
      for 1-7 years: a longitudinal study.
AB  - Implants with a small diameter may be used where bone width is reduced or in
      single-tooth gaps with limited mesiodistal space, such as for the replacement of
      lateral maxillary or mandibular incisors. The purpose of the present longitudinal
      study was to compare the prognosis of narrow implants (3.3-mm-diameter) to
      standard (4.1-mm-diameter) implants. Over a 7-year period, 122 narrow implants
      were inserted in 68 patients to support 45 partial fixed prostheses (PFD) and 23
      single-tooth prostheses (ST). Furthermore, 120 patients received 208 standard
      implants and were restored with 70 PFD and 50 ST, respectively. Clinical and
      radiographic assessment data were provided. Six (1.8%) out of 330 implants
      failed. Cumulative survival and success rates were calculated with life-table
      analyses processed by collecting clinical and radiographic data. For narrow
      implants, the cumulative survival rate was 98.1% in the maxilla and 96.9% in the
      mandible. The cumulative success rate was 96.1% in the maxilla and 92% in the
      mandible. Conversely, standard-diameter implants showed a cumulative survival
      rate of 96.8% in the maxilla and 97.9% in the mandible. The cumulative success
      rate was 97.6% in the maxilla and 93.8% in the mandible. Cumulative survival and
      success rates of small-diameter implants and standard-diameter implants were not
      statistically different (P > 0.05). Type 4 bone was a determining failure factor,
      while marginal bone loss was not influenced by the different implant diameters.
      The results suggest that small-diameter implants can be successfully used in the
      treatment of partially edentulous patients.

PMID- 16584410
TI  - Changes in the volume and density of calvarial split bone grafts after alveolar
      ridge augmentation.
AB  - OBJECTIVES: One main problem occurring after bone grafting is resorption, leading
      to insufficient bone volume and quality, and may subsequently cause dental
      implant failure. Comparison of graft volume and bone density of iliac crest and
      calvarial transplants determined by animal studies demonstrates significantly
      lower resorption of bone grafts harvested from the skull. This paper is the first
      clinical study evaluating bone volume and density changes of calvarial split bone
      grafts after alveolar ridge reconstruction. MATERIAL AND METHODS: Bone volume and
      density were determined using CT scans and the software program Dicom Works in a
      total of 51 calvarial grafts after alveolar ridge augmentation in 15 patients. CT
      scans were taken in all 15 patients immediately after grafting (T0) and before
      implantation after a postoperative period of 6 months (T1). In five patients (26
      calvarial grafts), a 1-year follow-up was performed (T2). RESULTS: A mean volume
      reduction of 16.2% at T1 (15 patients) and 19.2% at T2 (five patients) was
      observed. Bone density was high--about 1000 Hounsfield units--and did not change
      during the 1-year period. At the time of implantation, 41 transplants were
      classified as quality 1 bone and 10 as quality 2-3 bone. Grafting area and the
      technique used for grafting (inlay or onlay graft) did not affect the
      postoperative bone volume reduction. Generalized osteoporosis did not increase
      the resorption rate of calvarial transplants. CONCLUSION: Based on these
      findings, calvarial split bone grafts are a promising alternative for alveolar
      ridge reconstruction in dental implantology.

PMID- 16584411
TI  - Non-grafted sinus implants in periodontally compromised patients: a time-to-event
      analysis.
AB  - This study reports the results of implant therapy involving a sinus membrane lift
      and of conventional implant therapy in 68 periodontally compromised patients
      treated between June 1990 and June 2002. Patients had at least two implants
      inserted, one of which was placed in the maxillary sinus region following
      fenestration of the lateral sinus wall and lifting of the sinus membrane. Two
      implant systems were used: a two-stage system (Astra) and a one-stage system
      (ITI). Annual follow-up visits included recording of plaque, probing pocket depth
      and measurement of the radiographic distance in millimeter from the implant
      shoulder to the alveolar crest. Survival analysis showed that the proportion of
      implants that had not been explanted after 5 years ranged between 88.7% for ITI
      sinus implants and 97% for ASTRA conventional implants. After 10 years, the
      proportion of implants remaining in situ ranged between 59% for ITI conventional
      implants and 97% for ASTRA conventional implants. Cox regression analyses showed
      that the factors influential for implant explantation were implant type (HR(ITI)
      = 2.8), implant length (HR(< or = 10 mm) = 3.1), patient being a smoker
      (HR(smoking) = 2.2) and patient having at least 20 natural teeth (HR(> or = 20
      teeth) = 3.8). Our results demonstrate that sinus implants may be inserted with
      the same success as conventional implants in periodontally compromised patients.

PMID- 16584412
TI  - Tissue alterations at implant-supported single-tooth replacements: a 1-year
      prospective clinical study.
AB  - OBJECTIVES: The aim of this prospective study was to evaluate dimensional
      alterations of the peri-implant tissues at single-tooth restorations from the
      time of implant placement to 1-year post-loading. MATERIAL AND METHODS: Eleven
      patients, aged 18-36 years, subjected to single-tooth replacements with implant
      supported restorations (Branemark implant system) in the maxillary anterior
      region were included in the analysis. The implant installation was performed as a
      two-stage procedure with a 6-month healing interval. Bone dimensions were
      determined by direct assessments immediately following implant placement and at
      abutment connection. The prosthetic restoration was placed approximately 1 month
      after abutment surgery. Radiographic and clinical examinations were performed at
      crown placement and at 1-year post-loading. Assessments of the soft tissues at
      the implant site and at the neighboring teeth were performed before and during
      implant placement, before abutment connection, after crown placement and at the 1
      year follow-up examination. Mean values and standard deviations were calculated
      for each variable and interval, with the subject as the statistical unit.
      RESULTS: At the time of abutment connection, a mean loss of bone height at the
      facial and lingual aspect of the implant amounting to 0.7-1.3 mm (P < 0.05) was
      recorded, whereas no significant change was noted at proximal sites. A mean
      reduction of 0.4 mm of the labial bone thickness was observed between implant
      placement and the second-stage surgery. The radiographic bone-to-implant level
      showed a mean loss of 0.9 mm between abutment connection and crown placement
      (P<0.05) and a further 0.7 mm loss at 1 year (P < 0.05). The thickness of the
      labial mucosa was increased at crown placement followed by a slight remission at
      1 year. During the corresponding interval, a mean apical displacement of the
      labial soft tissue margin of 0.6 mm had taken place (P < 0.05). A papilla fill of
      > or = 50% was observed at a frequency of 32% at crown placement and 86% at 1
      year. CONCLUSIONS: The results demonstrated that following implant surgery
      remodeling takes place, which is manifested in diminished bone dimensions, both
      horizontally and vertically, at the facial aspect of the implant. The observed
      soft tissue alterations after the crown placement may affect the esthetic appeal
      of the restorative therapy.

PMID- 16584414
TI  - Intermittent loading improves results in mandibular alveolar distraction
      osteogenesis.
AB  - AIM: To evaluate clinical and morphological effects on distractive callus after
      application of an original protocol of bone stimulation. MATERIAL AND METHODS:
      Traditional or mechanically stimulated alveolar-distraction osteogenesis was
      studied on 16 highly selected subjects subdivided into two groups. Clinical,
      radiological, densitometric and histological (on biopsies) analyses were
      performed 6, 8 and 12 weeks after distraction was completed. RESULTS: In subjects
      undergoing stimulated alveolar-distraction osteogenesis, bone density was higher
      and at histology, bone with ordered structure was observed after 6 weeks.
      Moreover, bone trabeculae with oriented architecture and greater amounts of
      lamellar bone were observed after 8 and 12 weeks in the same subjects. DISCUSSION
      AND CONCLUSIONS: In conclusion, although osteogenic processes were similar in
      both groups, they were induced earlier and were better structured in subjects
      undergoing stimulated alveolar-distraction osteogenesis. These encouraging
      results can only be achieved and preserved by strict monitoring of distractive
      vectors.

PMID- 16584413
TI  - The effects of implant surface roughness and surgical technique on implant
      fixation in an in vitro model.
AB  - OBJECTIVES: The aim of the present study was to determine the relationship
      between implant surface parameters, surgical approach and initial implant
      fixation. MATERIAL AND METHODS: Sixty tapered, conical, screw-shaped implants
      with machined or etched surface topography were implanted into the explanted
      femoral condyle of goats. The implant sites were prepared either by a
      conventional technique, by undersized preparation, or by the osteotome technique.
      Peak insertion & removal torque, bone-to-implant contacts (BIC) and morphological
      bone appearance were assessed by scanning electron microscope (SEM) and micro
      computer tomography. (micro-CT). RESULTS: Insertion and removal torque values
      were significantly higher for etched implants inserted with the undersized
      technique (115.2 +/- 31.1, 102.9 +/- 36.4 N cm) respectively. Also, the average
      BIC value was higher for the etched implants placed with the undersized technique
      (87.5 +/- 5.6), which was statistically significant compared with machined and
      etched implants inserted by conventional technique. CONCLUSION: In conclusion,
      this study shows that the surgical technique has a decisive effect on implant
      fixation (represented in this study by installation torque value/removal torque
      value and histomorphometric evaluation) in trabecular bone. Nevertheless,
      additional in vivo studies have to be done to prove the importance of surgical
      protocol for the final implant-bone response.

PMID- 16584415
TI  - Osteogenic differentiation induced by bone morphogenetic proteins can be
      suppressed by platelet-released supernatant in vitro.
AB  - Both bone morphogenetic proteins (BMPs) and growth factors released from
      activated platelets both occur at sites of bone regeneration but their functional
      relationship to regulate the temporal and spatial sequence of cellular events is
      not well defined. Here we investigated whether supernatants derived from
      activated platelets can modulate the response of the osteogenic cell line MC3T3
      E1 to BMPs, and whether BMPs have an effect on MC3T3-E1 cells stimulated with
      platelet-released supernatant. Platelet-released supernatant suppressed BMP-2-,
      BMP-6-, and BMP-7-induced osteogenic differentiation of MC3T3-E1 cells, as
      indicated by the significant decrease in alkaline phosphatase activity and lower
      levels of osteocalcin transcripts, whereas BMP-2, BMP-6, and BMP-7 did not
      modulate migration and proliferation of MC3T3-E1 cells, which were stimulated
      with platelet-released supernatant. Osteogenic differentiation in response to
      BMPs was not affected after precultivation of MC3T3-E1 cells with platelet
      released supernatant. These data suggest that activated platelets can provide a
      microenvironment that temporarily suppresses the differentiation of osteogenic
      cells in the presence of BMPs. Future strategies to stimulate bone regeneration
      should take the suppression of BMP-induced osteogenic differentiation during the
      existence of the blood clot into account.

PMID- 16584416
TI  - Dental implants placement in conjunction with osteotome sinus floor elevation: a
      12-year life-table analysis from a prospective study on 588 ITI implants.
AB  - OBJECTIVES: The purpose of this prospective study was to evaluate the clinical
      success of placing ITI dental implants in the posterior maxilla using the
      osteotome technique. MATERIAL AND METHODS: All implants were placed following a
      one-stage protocol (elevating the sinus floor and placing the implant at the same
      time). Five hundred and eighty-eight implants were placed in 323 consecutive
      patients with a residual vertical height of bone under the sinus ranging from 6
      to 9 mm. The mean observation follow-up period was 59.7 months (with a range of
      12-144 months). This prospective study not only calculated the 12-year cumulative
      survival and success rates for 588 implants by life-table analysis but also the
      cumulative success rates for implant subgroups divided per implant length and the
      percentage of sinus membrane perforation were evaluated. RESULTS: The 12-year
      cumulative survival and success rates were 94.8% and 90.8%, respectively. The
      analysis of implant subgroups showed slightly more favourable cumulative success
      rates for 12 mm long implants (93.4%) compared with 10 and 8 mm long implants
      (90.5% and 88.9%, respectively). During the study period, only 13 perforations of
      the Schneiderian membrane were detected with a perforation rate of 2.2% (13
      perforations/601 treated sites). Ten perforations out of 13 were caused during
      the first half of the study period and of these, seven were detected during the
      first 3 years of this prospective study. CONCLUSION: Based on the results and
      within the limits of the present study, it can be concluded that ITI implant
      placement in conjunction with osteotome sinus floor elevation represents a safe
      modality of treating the posterior maxilla in areas with reduced bone height
      subjacent to the sinus as survival and success rates were maintained above 90%
      for a mean observation period of approximately 60 months. Shorter implants (8 mm
      implants) did not significantly fail more than longer ones (10 and 12 mm
      implants): the differences were small compared with the number of events; hence,
      no statistical conclusion could be drawn. But, from the clinical point of view,
      the predictable use of short implants in conjunction with osteotome sinus floor
      elevation may reduce the indication for complex invasive procedures like sinus
      lift and bone grafting procedures.

PMID- 16584417
TI  - Fast element mapping of titanium wear around implants of different surface
      structures.
AB  - The effect of unintended titanium release around oral implants remains a
      biological concern. The current study was undertaken to evaluate a new detection
      system of element mapping in biological probes. A new scanning electron
      microscopy-energy dispersive spectroscopy detection method was used to map the
      features of titanium contamination in peri-implant bone around implants with
      different surface structures. The amount of titanium wear was highest adjacent to
      titanium-plasma-sprayed surfaces, followed by sandblastered large grid acid
      etched and smooth surfaces. A high sensitivity of titanium detection over large
      areas of bone tissue was observed. A high spatial resolution of titanium wear
      particles (20 nm) could be reached and correlated to the ultrastructural
      morphological features of peri-implant tissue. Cells adjacent to titanium wear
      revealed no signs of morphological alterations on a nanoscale level at early
      periods of implant/bone interaction. The new technique may serve as a fast and
      effective tool to evaluate titanium release effects in biological probes.

PMID- 16584418
TI  - The in vitro effect of different PRP concentrations on osteoblasts and
      fibroblasts.
AB  - OBJECTIVES: The aim of this study was to assess the biological rationale for the
      use of platelet-rich plasma (PRP) by evaluating the effect of different
      concentrations of PRP on osteoblasts (OB) and fibroblasts (FB) function in vitro.
      MATERIAL AND METHODS: PRP was obtained from volunteer donors using standard
      protocols. Primary human cultures of oral FBs and OBs were exposed to both
      activated and non-activated plasma as well as various concentrations of PRP (2.5
      x, 3.5 x and max (4.2-5.5 x)). Cell proliferation was evaluated after 24 and 72 h
      using an MTT proliferation assay. Production of osteocalcin (OCN),
      osteoprotegerin (OPG) and transforming growth factor beta1 (TGF-beta1) was
      evaluated in OB after 24 and 72 h. Statistical analysis was performed using one
      way ANOVA. RESULTS: PRP-stimulated cell proliferation in both OBs and FBs. The
      effect of different PRP concentrations on cell proliferation was most notable at
      72 h. The maximum effect was achieved with a concentration of 2.5 x, with higher
      concentrations resulting in a reduction of cell proliferation. Upregulation of
      OCN levels and downregulation of OPG levels were noted with increasing PRP
      concentrations at both 24 and 72 h. TGF-beta1 levels were stimulated by
      increasing concentrations of PRP, with the increased levels being maintained at
      72 h. CONCLUSIONS: PRP preparations exert a dose-specific effect on oral FBs and
      OBs. Optimal results were observed at a platelet concentration of 2.5 x, which
      was approximately half of the maximal concentrate that could be obtained.
      Increased concentrations resulted in a reduction in proliferation and a
      suboptimal effect on OB function. Hence, different PRP concentrations may have an
      impact on the results that can be obtained in vivo.

PMID- 16584419
TI  - Clinical outcome of dental implants placed in fibula-free flaps used for the
      reconstruction of maxillo-mandibular defects following ablation for tumors or
      osteoradionecrosis.
AB  - OBJECTIVES: (a) To evaluate the clinical outcome of fibula revascularized flaps
      used for the reconstruction of maxillary and mandibular defects due to resection
      for tumors or osteoradionecrosis and (b) to evaluate the survival and success
      rates of implants placed in the reconstructed areas. MATERIAL AND METHODS: In a 8
      year period (1995-2002), 59 patients, 38 males and 21 females, aged from 13 years
      to 69 years (mean age: 48.7 years), presenting with maxillary and mandibular
      defects due to resection for tumors or osteoradionecrosis, were reconstructed
      with fibula-free flaps. Of the 59 patients, 16 received 71 implants for the
      prosthetic rehabilitation of the reconstructed edentulous areas. RESULTS: Out of
      59 fibula-free flaps, three failed and had to be removed, nine underwent partial
      necrosis involving the bone segment and/or the skin paddle but survived, while
      the remaining 47 healed uneventfully. The mean follow-up of patients after the
      reconstruction was 55 months (range: 24-120 months). The cumulative survival rate
      of fibula-free flaps was 94.9%. The mean follow-up of the 16 patients treated
      with dental implants and implant-supported prostheses was 50.2 months (range: 24
      96 months). The cumulative implant success and survival rates of implants were
      98.6% and 93.1% respectively. CONCLUSION: The reconstruction of maxillo
      mandibular defects following ablation for tumors or osteoradionecrosis with
      fibula-free flaps has been demonstrated to be a reliable technique with good long
      term results. Implants placed in the reconstructed areas were demonstrated to
      integrate normally, with success and survival rates comparable to those obtained
      in case of implants placed in native bone.

PMID- 16584420
TI  - Soft tissue around three different implant types after 1.5 years of functional
      loading without oral hygiene: a preliminary study in baboons.
AB  - The purpose of this study was to determine the peri-implant soft tissue dimension
      (PSD) and peri-implant bone level (BL) of dental implants with different designs
      and surface modifications after functional loading without oral hygiene. Three
      types of dental implants were placed in the posterior jaws of adult baboons,
      three of the same design per quadrant, and fitted with fixed partial dentures.
      After 1.5 years of functional loading and plaque accumulation, all implants
      showed severe peri-implant mucositis and comparatively high BL. A
      histomorphometric evaluation of the sulcus depth (SD), the dimension of the
      junctional epithelium (JE) and the connective tissue contact (CTC) resulted in no
      significant differences between the three implant designs, neither in the maxilla
      nor in the mandible (P>0.05). The sum of SD, JE and CTC forming the PSD was
      nearly the same in the maxilla (commercially pure titanium, CpTi: 3.5 mm 2.9/4.1
      confidence interval (CI); titanium plasma sprayed (TPS): 3.5 mm 2.9/4.2 CI; sand
      blasted acid-etched (GBAE): 3.2 mm 2.7/3.9 CI) and in the mandible (CpTi: 3.2 mm
      2.6/3.8 CI; TPS: 3.2 mm 2.6/3.8 CI; GBAE: 3.2 mm 2.7/3.9 CI; P>0.05). There was
      no difference in BL around the three implant designs (maxilla: CpTi: 0.9 mm
      0.5/1.6 CI; TPS: 0.9 mm 0.5/1.5CI; GBAE: 0.9 mm 0.5/1.6 CI; mandible: CpTi: 0.8
      mm 0.5/1.2 CI; TPS: 0.6 mm 0.4/0.9 CI; GBAE: 0.7 mm 0.5/1.1 CI; P>0.05). Overall,
      the data presented did not show any significant differences in peri-implant soft
      tissue conditions in baboons. Moreover, plaque accumulation and propagation of
      peri-implant mucositis after 1.5 years of functional loading was not influenced
      by implant design and surface modifications in baboons.

PMID- 16584421
TI  - Direct transfusion from donor to patient.

PMID- 16584422
TI  - Multiple-laboratory comparison of in vitro assays utilized to characterize
      hematopoietic cells in cord blood.

PMID- 16584423
TI  - Understanding the donor can correct the nation's blood imbalance.

PMID- 16584424
TI  - I want to say one word to you--just one word--"plastics".

PMID- 16584425
TI  - Multiple-laboratory comparison of in vitro assays utilized to characterize
      hematopoietic cells in cord blood.
AB  - BACKGROUND: Understanding the variability in results obtained by multiple
      laboratories is important because cord blood units are distributed worldwide for
      transplantation. STUDY DESIGN AND METHODS: Four exercises were conducted by
      multiple laboratories to assess assay variability on nucleated cell (NC),
      mononuclear cell (MNC) by hematology analyzers [HAs], and CD34+ cell (flow
      cytometry) measurements. Exercise 1 was an intralaboratory exercise in which the
      reproducibility of cell measurements was determined. Exercises 2 and 3 involved
      the shipment of identical processed cord blood samples. In Exercise 2, laboratory
      specific methods were utilized. In Exercise 3, two commercial CD34+ cell methods
      (Stem-Kit and TruCOUNT) were used. In Exercise 4, CD34+ cell levels were
      determined on repetitive regating of identical list-mode files. RESULTS:
      Intralaboratory reproducibility was highest for NC measurements and lowest for
      CD34+ cell measurements. In Exercise 2, all laboratories except one utilized HA
      with an impedance technology and determined comparable results for NC and MNC
      levels, whereas the other laboratory utilized a HA with an optical counting
      method. Substantial variation was observed on measuring CD34+ cells with ranges
      of 32 to 141, 32 to 66, and 25 to 116 CD34+ cells per microL for the three
      identical samples. In Exercise 3, on the use of one specific commercial assay,
      the ranges of CD34+ levels were 214 to 411 and 62 to 178 cells per microL for the
      two identical samples. Nearly all participating laboratories determined
      comparable CD34+ levels on the use of identical list-mode files. CONCLUSION:
      These studies indicate that substantial variability in CD34+ cell levels were
      determined with flow cytometry. The variability in NC and MNC levels was minimal
      with HA methodology.

PMID- 16584426
TI  - Clinical-scale expansion of human cytomegalovirus-specific cytotoxic T
      lymphocytes from peripheral blood mononuclear cells requiring single-peptide
      stimulation and feeder cells but not additional antigen-presenting cells.
AB  - BACKGROUND: The aim of this study was to find a simple and feasible method for ex
      vivo expansion of human cytomegalovirus (HCMV)-specific cytotoxic T cells from
      peripheral blood mononuclear cells (PBMNCs) without the aid of exogenous antigen
      presenting cells (APCs) such as cultured dendritic cells. STUDY DESIGN AND
      METHODS: PBMNCs from three HLA-A*2402-seropositive donors were stimulated with
      HCMV pp65(341-350) peptide on Day 1 and then cultured with interleukin-2 and
      allogeneic feeder cells for 3 to 4 weeks. HCMV peptide-specific T cells were
      purified with HLA-A*2402/pp65(341-350) tetramer on Days 12 to 13 and harvested on
      Days 23 to 27. RESULTS: The initial numbers of PBMNCs were 2 x 10(7), 1.5 x
      10(7), and 2.5 x 10(7) and the increases in HCMV peptide-specific T cells were
      3.5 x 10(4)-, 2.0 x 10(3)-, and 1.1 x 10(3)-fold, respectively. The estimated
      final numbers of tetramer-positive cells were 9.1 x 10(7), 9.0 x 10(6), and 5.3 x
      10(6), respectively. The purities of the tetramer-positive cell population in
      culture were 72.6, 75.0, and 80.9 percent, respectively. The cells killed peptide
      pulsed B-lympoblastoid cell lines and secreted interferon-gamma in a HLA
      restricted manner. They did not have natural killer cell activity or lymphokine
      activated killer cell activity. Most of them had an effector-memory phenotype.
      They did not express killer inhibitory receptors. CONCLUSION: This method makes
      it possible to obtain more than 1 x 10(7) HCMV-specific T cells from
      approximately 2 x 10(7) to 5 x 10(7) PBMNCs without exogenous APCs such as
      cultured dendritic cells.

PMID- 16584427
TI  - Implementation of peripheral blood CD34 analyses to initiate leukapheresis:
      marked reduction in resource utilization.
AB  - BACKGROUND: Analysis of the peripheral blood (PB) C34 value may determine the
      optimal time to initiate leukapheresis. STUDY DESIGN AND METHODS: After selecting
      a threshold PB CD34 value of five CD34 + cells per microL to initiate
      leukapheresis procedure, a prospective analysis of 50 consecutive patients was
      initiated to identify the optimal time to initiate leukapheresis and its impact
      on costs and resource utilization. Clinical decisions were made to commence or to
      postpone leukapheresis with this PB CD34 threshold number. Based on PB CD34
      values for each patient, the number of leukapheresis procedures, postponed or
      canceled, the number of CD34+ cells per kg, and the total number of cells
      collected were identified. Costs of mobilization were obtained from the hospital
      cost accounting system. RESULTS: In 13 months, 50 patients with a hematologic
      disorder underwent mobilization. There were 34 cancellations or postponements of
      collections due to a low PB CD34 value in 13 patients. By use of our identified
      costs per initial collection, this resulted in a savings of 67,660 US dollars.
      CONCLUSIONS: This prospective study defines how the implementation of the PB CD34
      value results in costs savings. A low PB CD34 value canceled or postponed a
      significant number of leukapheresis procedures, resulting in a substantial cost
      savings. Use of the PB CD34 value should be the standard of care during
      mobilization and peripheral blood progenitor cell collection.

PMID- 16584428
TI  - Instrument- and protocol-dependent variation in the enumeration of CD34+ cells by
      flow cytometry.
AB  - BACKGROUND: The information regarding the minimum number of CD34+ cells that are
      necessary to reconstitute hematopoiesis in patients undergoing peripheral blood
      progenitor cell transplantation is quite controversial. Some of the differences
      in these figures might be due to the selection of antibodies, staining protocols,
      and acquisition strategies for the flow cytometric enumeration of these cells.
      STUDY DESIGN AND METHODS: Twenty-seven human umbilical cord blood samples and 33
      leukapheresis products were consecutively collected for this study. Cells were
      stained following two different protocols, both using monoclonal antibodies to
      CD45 and CD34, and analyzed by the same operator in two different flow cytometers
      to enumerate the percentage of CD34+ mononuclear cells. RESULTS: Relevant
      differences in the proportion of cells were encountered, and the correlation
      between the results yielded by both instruments and protocols, although
      statistically valid, was suboptimal. CONCLUSIONS: Both interinstrument and
      interprotocol variation can provide additional explanation for the redundantly
      reported discrepancies concerning the numbers of CD34 cells that suffice to
      secure hemopoietic grafting. These results point to the need for new and
      different standardization approaches in this clinically relevant field.

PMID- 16584429
TI  - Whole-blood leukoreduction filters are a source for cryopreserved cells for
      phenotypic and functional investigations on peripheral blood lymphocytes.
AB  - BACKGROUND: Leukoreduction of blood is now widely performed by blood banks, and
      the possibility of recovering 10(8) to 10(9) white blood cells (WBCs) from
      leukoreduction filters, which are usually discarded, represents a promising
      source for normal human cells. Previous studies with these filters to prepare
      WBCs have performed their experimentation with fresh cells only. Whether these
      filter-derived cells could also be used to prepare frozen cell banks to
      facilitate work organization and open new avenues for their utilization as
      references in physiological studies and clinical investigations was investigated.
      STUDY DESIGN AND METHODS: Blood samples or whole-blood leukoreduction filters
      were obtained, after informed consent, from volunteers or blood donors,
      respectively. The proportions of CD3+, CD14+, CD16+, CD19+, and CD45+ cells
      within peripheral blood mononuclear cells (PBMNCs) were determined by flow
      cytometry from all samples. B cells were isolated and their functional responses
      were evaluated in vitro. RESULTS: The yield of PBMNCs recovered from whole-blood
      leukoreduction filters was lower (50%) than the one with fresh blood samples but
      still provided 2 x 10(8) to 4 x 10(8) PBMNCs per unit. After one cycle of
      freezing-thawing, the proportions of B- and T-cell populations were similar to
      normal blood values. Purified B cells issued from whole-blood leukoreduction
      filters displayed normal phenotypes and functions. CONCLUSION: Leukoreduction
      filters represent a valuable source of PBMNCs. These cells could be easily
      recovered to prepare frozen cell banks useful in basic phenotypic and functional
      analyses involving the main subsets of B cells and the global T-cell population.

PMID- 16584430
TI  - Convenience, the bane of our existence, and other barriers to donating.
AB  - BACKGROUND: To prevent donor loss and improve retention, it is important to
      understand the major deterrents to blood donation and to identify factors that
      can be effectively addressed by blood centers. STUDY DESIGN AND METHODS: A 30
      item self-administered questionnaire was completed in 2003 by 1705 first-time and
      2437 repeat US donors who had not donated in 2 to 3 years. Asian, Hispanic,
      black, and white first-time and repeat donors rated the importance of deterrents
      to donation in their decision to not return with a 1 to 5 scale. Categorical
      analysis of variance methods were used to compare the importance of deterrents
      between first-time and repeat donors of different race or ethnicity. RESULTS: Not
      having a convenient place to donate was most commonly cited as an important or
      very important reason for not returning by 32 to 42 percent of first-time and 26
      to 43 percent of repeat respondents. Although bad treatment and poor staff skills
      were less of a barrier than convenience, they were more important for minority
      donors. Other factors such as physical side effects, foreign travel, or length of
      the process appeared less important. CONCLUSION: Inconvenience is a major barrier
      to donating, suggesting that mobile collections and increased hours of operation
      might help recapture lapsed donors. The finding that lapsed minority donors were
      more likely to give bad treatment and poor staff skills as important reasons to
      not donate is disconcerting in light of the changing donor demographics and
      increased efforts to recruit these donors.

PMID- 16584431
TI  - Use of sequence variation in three highly variable regions of the mitochondrial
      DNA for the discrimination of allogeneic platelets.
AB  - BACKGROUND: Human mitochondrial DNA (mtDNA) polymorphisms can be used to detect
      allogeneic transfused platelets. To increase the number of informative
      polymorphisms we investigated three hypervariable regions (HVR1, HVR2, and HVR3)
      within the displacement loop (D-loop) region of the mtDNA. STUDY DESIGN AND
      METHODS: mtDNA was obtained from 119 unrelated blood donors. Forward and reverse
      primers were designed and conditions optimized to amplify and sequence the
      template mtDNA by dye terminator cycle sequencing. RESULTS: We established a
      sequencing protocol for all three HVRs of the mtDNA. Polymorphic sites were found
      in all three regions: 66 in HVR1, 44 in HVR2, and 18 in HVR3. Combining the
      sequence information of HVR1, -2, and -3 resulted in 105 different genotypes of
      which 95 were unique. We were able to discriminate between two randomly chosen
      individuals with a random match probability of 1.2 percent. CONCLUSION: The D
      loop region of mtDNA contains a wealth of informative molecular markers for
      chimerism and survival studies after transfusions of cellular blood components.

PMID- 16584432
TI  - Pathogen inactivation of platelets with a photochemical treatment with amotosalen
      HCl and ultraviolet light: process used in the SPRINT trial.
AB  - BACKGROUND: A photochemical treatment (PCT) system has been developed to
      inactivate a broad spectrum of pathogens and white blood cells in platelet (PLT)
      products. The system comprises PLT additive solution (PAS III), amotosalen HCl, a
      compound adsorption device (CAD), a microprocessor-controlled ultraviolet A light
      source, and a commercially assembled system of interconnected plastic containers.
      STUDY DESIGN AND METHODS: A clinical prototype of the PCT system was used in a
      large, randomized, controlled, double-blind, Phase III clinical trial (SPRINT)
      that compared the efficacy and safety of PCT apheresis PLTs to untreated
      apheresis PLTs. The ability of multiple users was assessed in a blood center
      setting to perform the PCT and meet target process specifications. RESULTS: Each
      parameter was evaluated for 2237 to 2855 PCT PLT products. PCT requirements with
      respect to mean PLT dose, volume, and plasma content were met. Transfused PCT PLT
      products contained a mean of 3.6 x 10(11) +/- 0.7 x 10(11) PLTs. The clinical
      process, which included trial-specific samples, resulted in a mean PLT loss of
      0.8 x 10(11) +/- 0.6 x 10(11) PLTs per product. CAD treatment effectively reduced
      the amotosalen concentration from a mean of 31.9 +/- 5.3 micromol per L after
      illumination to a mean of 0.41 +/- 0.56 micromol per L after CAD. In general,
      there was little variation between sites for any parameter. CONCLUSIONS: The PCT
      process was successfully implemented by 12 blood centers in the United States to
      produce PCT PLTs used in a prospective, randomized trial where therapeutic
      efficacy of PCT PLTs was demonstrated. Process control was achieved under blood
      bank operating conditions.

PMID- 16584433
TI  - Reevaluation of the resting time period when preparing whole blood-derived
      platelet concentrates with the platelet-rich plasma method.
AB  - BACKGROUND: The resting of platelet (PLT) pellets during the preparation of whole
      blood-derived PLT concentrates (PCs) is considered an essential step. A
      reevaluation of the rest period was conducted because preparation and storage
      conditions have been modified during the past 20 years. STUDY DESIGN AND METHODS:
      A two-site in vitro study (Study 1) was conducted with rest times of 0 to 5
      minutes, 1 hour, and 4 hours (n = 31-33 per rest period). Leukoreduced PCs were
      stored for 5 days. A second study (Study 2) measuring in vivo viability was
      conducted at a third site (14 paired studies). PCs were prepared from 2 units of
      whole blood on the same day to simultaneously compare viability following storage
      and radioisotopic labeling. RESULTS: In Study 1, comparable in vitro parameters
      and swirling were observed with the three rest periods. The mean (+/-1 SD) values
      after storage for the extent of shape change and hypotonic stress parameters were
      0 to 5 minutes, 16.7 +/- 7.2 and 66.0 +/- 15.7%; 1 hour, 19.1 +/- 6.9 and 69.3 +/
      17.9%; and 4 hours, 17.6 +/- 5.5 and 64.1 +/- 11.3%. In Study 2, the in vivo
      recovery was 49.9 +/- 15.3 and 50.9 +/- 20.2% with 0- to 5-minute and 1-hour rest
      periods, respectively. The corresponding survival time was 111.2 +/- 50.7 and
      114.9 +/- 43.8 hours. CONCLUSION: These studies indicate comparable in vitro and
      in vivo viability properties with 0- to 5-minute and 1-hour rest periods and at 4
      hours (in vitro only).

PMID- 16584434
TI  - A high-resolution, double-labeling method for the study of in vivo red blood cell
      aging.
AB  - BACKGROUND: Red blood cell (RBC) senescence is a process that has received
      considerable study, yet remains poorly understood. This has been primarily due to
      the difficulty in isolating a RBC cohort of narrowly distributed, well-defined
      age. Biotin labeling has previously been used to produce an identifiable cell
      cohort of known mean age; however, the variability of RBC age within the cohort
      is relatively large for most of its existence. Treatments typically employed on
      animal subjects to reduce this variability can perturb erythropoiesis and result
      in abnormal RBC aging. STUDY DESIGN AND METHODS: The objective of this study was
      to improve on the traditional in vivo biotinylation method by introducing a
      chemically distinct, second labeling step. In this case, digoxigenin was used to
      label cells 1 to 2 days before the injection of biotin. RESULTS: It was shown, in
      the rat, that two identifiable subpopulations of labeled RBCs can be followed
      over time: a broad, double-labeled cohort and a narrow, single-labeled cohort,
      the latter consisting of only those cells created between the first and second
      labeling steps. The utility of this technique was demonstrated by observing the
      age-dependent exposure of phosphatidylserine in the single-labeled RBCs.
      CONCLUSION: Its capacity to generate a cohort of narrowly distributed age,
      without the adverse effects associated with animal treatment, should make this a
      useful method for the study of RBC senescence.

PMID- 16584435
TI  - The effect of whole-blood storage time on the number of white cells and platelets
      in whole blood and in white cell-reduced red cells.
AB  - BACKGROUND: Whole blood (WB) can be stored for some time before it is processed
      into components. After introduction of universal white cell (WBC) reduction, it
      was observed that longer WB storage was associated with more residual WBCs in the
      WBC-reduced red cells (RBCs). Also, weak propidium iodide (PI)-positive events
      were observed in the flow cytometric WBC counting method, presumably WBC
      fragments. The effect of storage time on the composition of WB and subsequently
      prepared WBC-reduced RBCs was studied. STUDY DESIGN AND METHODS: WB was collected
      in bottom-and-top collection systems with inline filters, obtained from Baxter,
      Fresenius, or MacoPharma. Units were stored at room temperature and separated
      into components in 4-hour intervals between 4 and 24 hours after collection. RBCs
      were WBC-reduced by inline filtration (approx. 50/group). RESULTS: Platelet (PLT)
      counts were lower in WB stored for 4 to 8 hours compared to 20 to 24 hours (mean
      +/- SD): 79 +/- 31 versus 102 +/- 30 for Baxter (p < 0.01); 91 +/- 31 versus 101
      +/- 35 for Fresenius (not significant); and 73 +/- 47 versus 97 +/- 31 (all x
      10(9) per unit) for MacoPharma (p < 0.01), respectively. The median residual WBC
      counts in WBC-reduced RBCs for WB stored for 4 to 8 and 20 to 24 hours were 0.03
      versus 0.17 for Baxter (p < 0.001), 0.00 versus 0.06 for Fresenius (p < 0.001),
      and 0.13 versus 0.26 (all x 10(6) per unit) for MacoPharma (not significant),
      respectively. All WBC-reduced RBCs contained fewer than 5 x 10(6) WBCs per unit.
      A longer storage time of WB was associated with more weak PI-positive events,
      irrespective of the filter. CONCLUSION: Longer storage of WB before processing
      results in counting higher numbers of PLTs in WB, higher numbers of WBCs in WBC
      reduced RBCs, and more weak PI-positive events.

PMID- 16584436
TI  - Comparison of the effects of aprotinin and tranexamic acid on blood loss and red
      blood cell transfusion requirements during the late stages of liver
      transplantation.
AB  - BACKGROUND: During liver transplantation (LT), profound activation of the
      fibrinolytic system can contribute significantly to perioperative bleeding.
      Prophylactic administration of antifibrinolytic agents has been shown to reduce
      blood loss and the need for allogeneic transfusion in these conditions. STUDY
      DESIGN AND METHODS: This prospective randomized trial included 51 cirrhotic
      patients undergoing LT. Patients were randomly assigned to receive either 280 mg
      of aprotinin (AP) followed by 70 mg per hour or 40 mg per kg tranexamic acid (TA)
      followed by 40 mg per kg per hour, administered from the end of the anhepatic
      phase until 2 hours after reperfusion of the graft, and the effects on blood loss
      and red blood cell (RBC) transfusion requirements were compared. Transfusion
      policy was standardized in all patients. In addition, the biological effects of
      the two drugs, as assessed by coagulation and fibrinolytic markers obtained
      during surgery, were evaluated in a subgroup of patients from each treatment
      group and compared with an historical control group that did not receive
      antifibrinolytic drugs. RESULTS: There was no significant difference between the
      two groups in perioperative blood losses (AP, 6200 [4620-8735] mL; TA, 5945 [4495
      8527] mL; median [range]) or in RBC transfusions requirements (AP, 9 [6.75-15.25]
      units; TA, 10 [6.5-13.5] units). Inhibition of fibrinolysis was observed with
      both drugs compared with the control group. Coagulation appeared to be activated
      more with AP, however, whereas fibrinolysis was inhibited more by TA. CONCLUSION:
      Blood losses and RBC transfusion requirements were comparable regardless of the
      drug administered. TA may be as valuable as AP for controlling fibrinolysis in
      LT.

PMID- 16584437
TI  - RHD(T201R, F223V) cluster analysis in five different ethnic groups and serologic
      characterization of a new Ethiopian variant DARE, the DIII type 6, and the
      RHD(F223V).
AB  - BACKGROUND: The RHD phylogeny in humans shows four main clusters of which three
      are predominantly observed in (African) black persons. Each of the African
      clusters is characterized by specific amino acid substitutions relative to the
      Eurasian RHD allele. RH phylogeny defines the framework for identification of
      clinically relevant aberrant alleles. This study focuses on the weak D type 4
      cluster (characterized by RHD(T201R, F223V) (602C>G 667T>G)) in five ethnic
      groups. STUDY DESIGN AND METHODS: A total of 1702 samples were screened for the
      presence of 602C>G and 667T>G by sequence-specific polymerase chain reaction (PCR
      SSP). Eighty samples were assigned to the weak D type 4 cluster and were
      molecularly characterized by PCR-SSP and RHD sequencing. Antigens of aberrant
      alleles were characterized with monoclonal anti-D according to the 37-epitope
      model when possible. RESULTS: Five new aberrant alleles, DIII type 6, DIII type
      7, DARE, RHD(T201R, F223V) (without 819G>A), and RHD(F223V), were identified and
      DIII type 6, DARE, and RHD(F223V) were serologically characterized with
      monoclonal anti-D. Both the DARE and RHD(F223V) showed epitope loss. It is
      postulated that the 1136C>T nucleotide substitution (characteristic for the DAU
      allele cluster) is present on the DVa(KOU) allele. CONCLUSION: Identification of
      the new variant alleles refines the phylogeny of RHD in humans. The proposed
      DVa(KOU) allele with 1136C>T (DVa(KOU)T379M) is probably caused by conversion of
      the DAU0 allele and the DVa(KOU) allele, forming a phylogenetic link between the
      DV allele and the DAU cluster. By describing the RHD(F223V) (602C>G) and
      RHD(T201R, F223V) (602C>G and 667T>G) alleles formal proof is given for the
      origin of the non-Eurasian cluster.

PMID- 16584438
TI  - The D category VI type 4 allele is prevalent in the Spanish population.
AB  - BACKGROUND: The D category VI (DVI) is one of the clinically most important
      partial D. Three different molecular structures causing the DVI phenotype have
      been described. STUDY DESIGN AND METHODS: To determine the molecular basis of the
      DVI phenotype in the Spanish population, 20 DVI samples, previously detected in
      serologic screening, were examined by polymerase chain reaction with RHD exon
      specific primers. Unexpected findings were further pursued by cDNA nucleotide
      sequencing. RESULTS: A novel pattern of RHD exon amplification was detected,
      which did not correspond to any of the previously described molecular structures.
      The cDNA sequence led to the identification of the new hybrid RHD-Ce(3-5)-D
      allele. The origin of exon 2 is undeterminable, because the 5' breakpoint was
      located within a region of RHD and RHCE identical sequence, which encompasses
      this exon. Sequencing of intron 5 allowed the 3' breakpoint to be mapped between
      the sixth and seventh polymorphic sites. Serologically, the hybrid protein has a
      D epitope expression pattern identical to the previously described DVI phenotypes
      and an antigen density slightly lower than DVI type 3. The new DVI variant is
      linked to the DCe haplotype and expresses the low-incidence BARC antigen.
      CONCLUSION: A novel structure causing the DVI phenotype, here named DVI type 4,
      has been characterized. This novel structure is the most frequent cause of DVI in
      Spain.

PMID- 16584439
TI  - Anticoagulation with low-molecular-weight heparin (dalteparin) in plasmapheresis
      therapy: initial experience.
AB  - BACKGROUND: In contrast to other extracorporeal treatments no established regime
      exists for anticoagulation with low-molecular-weight heparin (LMWH) in
      plasmapheresis therapy. A study was conducted to investigate whether LMWH
      (dalteparin-Na) is suitable as an effective anticoagulant in plasmapheresis
      therapy. STUDY DESIGN AND METHODS: Eleven patients with autoimmune neurological
      diseases and the necessity for a plasmapheresis therapy were enrolled. A
      capillary membrane filter was used. A total of 2000 mL of human plasma was
      isovolumetrically exchanged per plasmapheresis cycle. The anticoagulation was
      accomplished with a single bolus of LMWH (dalteparin) of 80 to 90 IU per kg of
      body weight. The system was visually monitored. Anti-factor (F)Xa activity,
      thrombin-antithrombin III complex (TAT), and prothrombin fragment 1+2 (F 1+2)
      were determined at regular intervals. Samples were taken from the collected
      plasma pool to determine the loss of LMWH during the plasmapheresis procedure.
      RESULTS: All plasmapheresis cycles with LMWH were successful without
      complications. Approximately 40 percent of the initially administered LMWH bolus
      was lost by the large porous filter during the plasmapheresis. The anti-FXa
      values were determined to be 0.5 IU per mL during the entire plasmapheresis. TAT
      values were elevated (TAT median, 14.3 microg/L). F 1+2 values measured before
      the filter cartridge remained within the normal range for the entire
      plasmapheresis cycle (<1.2 nmol/L) and were increasingly elevated after the
      filter. CONCLUSION: Our initial experiences with LMWH for anticoagulation in
      plasmapheresis indicate that a body weight adjusted dose of LMWH (dalteparin) is
      suitable for anticoagulation in plasmapheresis therapy. No complications were
      observed. The data are encouraging. Further investigations will show if and how
      the present anticoagulation regime could be further optimized.

PMID- 16584440
TI  - Additional red blood cell alloantibodies after blood transfusions in a
      nonhematologic alloimmunized patient cohort: is it time to take precautionary
      measures?
AB  - BACKGROUND: Red blood cell (RBC) alloimmunization is common in transfused
      patients. Most studies report on the rate of alloimmunization in chronically
      transfused patients, which can be as high as 60 percent. Less is known on the
      incidence of clinically relevant antibodies in accidentally transfused patients.
      Because the probability of repeat transfusion increases with longer life
      expectancy, it was wondered to which extend non-chronically transfused
      alloimmunized patients are prone to form additional antibodies after repeat
      transfusion events. STUDY DESIGN AND METHODS: A 20-year retrospective multicenter
      study was performed analyzing additional alloantibody formation, against the RH,
      KEL, FY, JK, and MNS blood group systems. RESULTS: After additional transfusions,
      21.4 percent of 653 patients produced additional antibodies, resulting in 157 new
      antibody specificities. At the end of the study 33.4 percent of patients had
      multiple antibodies. Eighty of 140 patients (57%) who formed additional
      antibodies did so after one transfusion episode of a median of 2 units of RBCs.
      Based on the antigen profile of 316 patients, 83 percent of antibodies could have
      been prevented by extended matching for the C, E, c, K, Fy(a), and Jk(a)
      antigens. Considering the current available donors in our region, 1 to 10 percent
      of potential donors would be available for 39 percent of patients and greater
      than 10 percent of potential donors for 61 percent of patients. CONCLUSION: It
      has been shown that nonhematooncologic alloimmunized patients are high antibody
      responders, with a more than 20 times increased risk to form antibodies compared
      to first-time alloimmunization risk. If extended matching for C, c, E, K, Fy(a),
      and Jk(a) antigens in the future is considered, this group should be taken into
      account.

PMID- 16584441
TI  - Summary of the AABB Interorganizational Task Force on Bacterial Contamination of
      Platelets: Fall 2004 impact survey.
AB  - BACKGROUND: New voluntary standards in the United States regarding bacterial
      contamination of platelets (PLTs) led to the formation of the AABB
      Interorganizational Task Force on Bacterial Contamination of Platelets. This
      article summarizes a survey conducted by the Task Force to assess the impact of
      bacterial detection. STUDY DESIGN AND METHODS: An Internet-based survey of AABB
      member institutions was conducted from September 17, 2004, to October 1, 2004.
      The survey was designed principally to assess PLT usage, supply, and outdating
      and the currently used bacteria detection methods. RESULTS: Of 900 facilities
      surveyed, 350 responded (38%). These facilities collected approximately 43.3 and
      65.9 percent and transfused approximately 19.1 and 22.2 percent of the whole
      blood-derived PLT concentrates (WBPCs) and apheresis PLTs in the United States,
      respectively. Most facilities (64-91%) indicated that their ability to provide
      PLTs for transfusion had not been affected. Approximately half (50-57.1%)
      indicated no changes in their PLT inventory. Two-thirds (66-68%) indicated no
      increased PLT outdating. More than 90 percent of apheresis PLTs are tested with a
      culture-based method, whereas WBPCs are tested with a variety of methods (mostly
      non-culture-based) resulting in a 4.6-fold decrease in the confirmed positive
      detection rate compared with apheresis PLTs (p < 0.001). CONCLUSION: After the
      implementation of AABB Standard 5.1.5.1, the majority of facilities responding to
      this survey experienced no (or modest) impact on PLT availability or outdating.
      Nevertheless, a substantial portion of facilities experienced both increased
      outdating and decreased availability. Some facilities were greatly impacted.
      Based on the data gathered, it is impossible to conclude whether such shortages
      resulted from production or distribution problems or were due to decreased shelf
      life and increased outdates.

PMID- 16584442
TI  - Functional inactivation of white blood cells by Mirasol treatment.
AB  - BACKGROUND: The presence of white blood cells (WBCs) in blood products has been
      shown to contribute to the development of a variety of immune responses including
      both donor antirecipient and recipient antidonor responses. Mirasol PRT treatment
      is a pathogen reduction protocol that is based on the inactivation of nucleic
      acid replication after exposure to riboflavin and light and was tested for its
      ability to inactivate nucleated WBC function. STUDY DESIGN AND METHODS: Sets of
      paired WBCs from different donors who either had received Mirasol treatment or
      were untreated were tested for their ability to be activated in response to
      phorbol myristic acetate (PMA); to proliferate in response to stimuli including
      phytohemagglutinin PHA, anti-CD3+ anti-CD28, or allogeneic stimulator cells; to
      stimulate proliferation by allogeneic responder cells; and to produce cytokines
      in response to lipopolysaccharide (LPS) and anti-CD3+ anti-CD28. RESULTS:
      Although Mirasol PRT treatment did not significantly change the distribution of
      human lymphocyte subpopulations, there were significant functional changes.
      Mirasol PRT treatment inhibited activation in response to PMA and completely
      inhibited proliferation in response to PHA, anti-CD3+ anti-CD28, or allogeneic
      stimulator cells. Mirasol PRT treatment also prevented the cells' ability to act
      as antigen-presenting cells and the ability to produce cytokines in response to
      stimuli such as LPS or anti-CD3+ anti-CD28. CONCLUSIONS: Mirasol PRT treatment is
      able to functionally inactivate WBCs in blood products along with inactivating
      pathogens and should prevent immunological consequences resulting from the
      presence of WBCs in blood products.

PMID- 16584443
TI  - Streptococcus agalactiae sepsis after transfusion of a plateletpheresis
      concentrate: benefit of donor evaluation.
AB  - BACKGROUND: Bacterial contamination of platelet (PLT) components is an important
      cause of transfusion reactions. Recent efforts have focused on heightened
      surveillance to detect contamination before transfusion to limit recipient
      morbidity and mortality. Although identifying the cause of contamination is most
      often viewed in the context of recipient safety, this case illustrates the
      importance of a thorough evaluation on donor safety. CASE REPORT: A 68-year-old
      woman experienced a severe febrile reaction after a plateletpheresis transfusion.
      Blood cultures from the patient and from the plateletpheresis component were both
      positive for the presence of Streptococcus agalactiae. No abnormalities were
      identified on review of collection and processing records. The donor was
      asymptomatic and had a negative review of systems, a normal physical exam, normal
      laboratory values, and negative blood and urine cultures. One of three stool
      samples was positive for the presence of occult blood. Colonoscopy revealed a
      Dukes Stage B colonic adenocarcinoma. Fifteen months after surgical resection and
      adjuvant chemotherapy, the donor had no evidence of recurrent tumor. CONCLUSION:
      Identification of bacteria in blood components should trigger a comprehensive
      donor evaluation, particularly if donor bacteremia is suspected. Organisms that
      may be associated with an enteric source should prompt a thorough
      gastrointestinal evaluation. Because the primary reservoir of S. agalactiae in
      the human body is the gastrointestinal tract, and because no findings suggested
      an alternate portal of entry in our male donor, a gastrointestinal source was
      suspected. In this case, an evaluation for organism-specific pathology led to
      early identification of a potentially curable large bowel lesion.

PMID- 16584444
TI  - Preparation of soluble infectious samples from scrapie-infected brain: a new tool
      to study the clearance of transmissible spongiform encephalopathy agents during
      plasma fractionation.
AB  - BACKGROUND: Concern about the safety of blood, blood components, and plasma
      derived products with respect to prions has increased since the report of two
      blood-related infections of variant Creutzfeldt-Jakob disease in the United
      Kingdom. Efforts were directed toward the development of procedures able to
      remove or inactivate prions from blood components or plasma-derived products with
      brain fractions of transmissible spongiform encephalopathy (TSE)-infected rodents
      as spiking materials. These spiking materials, however, are loaded with
      pathological prion protein (PrP(TSE)) aggregates that are likely not associated
      to blood infectivity. The presence of these aggregates may invalidate these
      studies. STUDY DESIGN AND METHODS: Brains from 263K scrapie-infected hamsters
      were suspended in 10 percent phosphate-buffered saline. After low-speed
      centrifugation, the supernatant was collected and ultracentrifuged at 220,000 x g
      at 25 degrees C for 30 minutes. The high-speed supernatants (S(HS)) and pellets
      were collected; the proteinase-resistant PrP(TSE) was measured by Western blot
      and infectivity by intracerebral inoculation into weanling hamsters. RESULTS: A
      substantial amount of prion infectivity (more than 10(5) LD(50) per mL of a 10%
      suspension of brain tissues) is present in the S(HS) fraction of 263K scrapie
      infected hamster brains. Concomitantly, this fraction contains none or only
      traces of PrP(TSE) in its aggregate form. CONCLUSION: This study describes a
      simple and fast protocol to prepare infectious material from 263K scrapie
      infected brains that is not contaminated with PrP(TSE) aggregates. This S(HS)
      fraction is likely to be the most relevant material for endogenous spiking of
      human blood in validation experiments aimed at demonstrating procedures to remove
      or inactivate TSE infectious agents.

PMID- 16584445
TI  - Monocytes-macrophages are a potential target in human infection with West Nile
      virus through blood transfusion.
AB  - BACKGROUND: West Nile virus (WNV) transmission by transfusion was documented in
      2002. Approximately 80 percent of WNV infections are asymptomatic and 1 percent
      develop severe neurological illness. In animals, Langerhans-dendritic cells
      support initial viral replication, followed by replication in lymphoid tissues
      and dissemination to organs and possibly to the CNS. The cellular tropism of WNV
      infection after transfusion and the particular human blood cells that sustain
      viral replication remain largely unknown. Whether primary monocyte-derived
      macrophages (MDMs) support WNV infection-replication and produce infectious
      virions, with an in vitro system, was investigated. STUDY DESIGN AND METHODS:
      Elutriated monocytes (CD33+/CD14+) from suitable blood donors were cultured in
      the presence of macrophage-colony-stimulating factor, infected with WNV-NY99 at
      different time points, washed, and cultivated for up to 47 days. Supernatants
      were tested for WNV replication by TaqMan reverse transcription-polymerase chain
      reaction (RT-PCR), with primers for the envelope and/or 3'NC regions, and by cDNA
      PCR to detect WNV minus-strand RNA and for the presence of functional virions by
      infectivity assays in Vero cells. RESULTS: RT-PCR TaqMan of supernatants
      demonstrated productive infection of MDMs. Viral load reached 2 to 5 log above
      baseline in 3 to 6 days and then declined, with detectable viral replication
      persisting for up to 47 days. WNV minus-strand RNA was detected in Day 4
      cultures, indicating active viral replication. Infected MDM cultures showed no
      cytopathic changes. Supernatants that were TaqMan-positive for the presence of
      WNV-infected Vero cells and produced cytopathic effects within 3 to 5 days of
      culture. CONCLUSION: The susceptibility of monocytes-macrophages to productive
      infection in vitro is compatible with a potential role in initial WNV replication
      and propagation after transmission by transfusion.

PMID- 16584446
TI  - The Lutheran glycoprotein: a multifunctional adhesion receptor.
AB  - The Lutheran blood group system, which comprises one of the largest families of
      human red blood cell (RBC) antigens, resides on two immunoglobulin superfamily
      (IgSF) proteins: Lutheran and basal cell adhesion molecule (B-CAM). These two
      glycoproteins arise via alternative splicing of mRNA from a single gene and
      differ in structure only in the lengths of their cytoplasmic tails. Both are
      expressed on RBCs as well as a variety of other cell types, and they are
      overexpressed on sickle RBCs (SS RBC). B-CAM/Lu is the critical receptor for SS
      RBC adhesion to the extracellular matrix protein laminin, an interaction thought
      to contribute to the pathogenesis of sickle cell-related vasoocclusive events.
      Recent work has also shown that B-CAM/Lu on RBCs can undergo activation as a
      result of adrenergic signaling pathways. The high affinity of B-CAM/Lu for
      laminin is also thought to contribute to various developmental processes,
      including organogenesis, vascular development, erythropoiesis, and smooth muscle
      development and organization. Interestingly, the B-CAM spliceoform seems to be
      overexpressed by a variety of different malignant tumors and may be involved,
      along with other adhesion receptor proteins, in malignant transformation and
      tumor metastasis. Studies of B-CAM/Lu have thus expanded from defining antigen
      specific polymorphisms to investigations of processes involved in sickle cell
      disease, human development, and cancer biology.

PMID- 16584448
TI  - Donor screening for agents of bioterror.

PMID- 16584449
TI  - Fatal septic shock associated with transfusion-transmitted Serratia marcescens.

PMID- 16584450
TI  - AHRQs National Healthcare Quality and Disparities Reports: resources for health
      services researchers.

PMID- 16584451
TI  - Quality improvement implementation and hospital performance on quality
      indicators.
AB  - OBJECTIVE: To examine the association between the scope of quality improvement
      (QI) implementation in hospitals and hospital performance on selected indicators
      of clinical quality. DATA SOURCES: Secondary data from 1997 mailed survey of
      hospital QI practices, Medicare Inpatient Database, American Hospital
      Association's Annual Survey of Hospitals, the Bureau of Health Professions' Area
      Resource File, and two proprietary data sets compiled by Solucient Inc.
      containing data on managed care penetration and hospital financial performance.
      STUDY DESIGN: Cross-sectional study of 1,784 community hospitals to assess
      relationship between QI implementation approach and six hospital-level quality
      indicators. DATA COLLECTION/ABSTRACTION METHODS: Two-stage instrumental variables
      estimation in which predicted values (instruments) of four QI scope variables and
      control (exogenous) variables used to estimate hospital-level quality indicators.
      PRINCIPAL FINDINGS: Involvement by multiple hospital units in QI effort is
      associated with worse values on hospital-level quality indicators. Percentage of
      hospital staff and percentage of senior managers participating in formally
      organized QI teams are associated with better values on quality indicators.
      Percentage of physicians participating in QI teams is not associated with better
      values on the hospital-level quality indicators studied. CONCLUSIONS: Results
      supported the proposition that the scope of QI implementation in hospitals is
      significantly associated with hospital-level quality indicators. However, the
      direction of the association varied across different measures of QI
      implementation scope.

PMID- 16584452
TI  - Predicting nursing facility residents' quality of life using external indicators.
AB  - PURPOSE: A newly developed brief measure of nursing facility (NF) resident self
      reported quality of life (QOL) has been proposed for inclusion in a modified
      version of the minimum data set (MDS). There is considerable interest in
      determining whether it is possible to develop indicators of QOL that are more
      convenient and less expensive than direct, in-person interviews with residents.
      DESIGN AND METHODS: QOL interview data from 2,829 residents living in 101 NFs
      using a 14-item version of a longer instrument were merged with data from the MDS
      and the Online Survey and Certification Automated Record (OSCAR). Bivariate and
      multivariate hierarchical linear modeling were used to assess the association of
      QOL with potential resident and facility level indicators. RESULTS: Resident and
      facility level indicators were associated with self-reported QOL in the expected
      direction. At the individual resident level, QOL is negatively associated with
      physical function, visual acuity, continence, being bedfast, depression, conflict
      in relationships, and positively associated with social engagement. At the
      facility level, QOL is negatively associated with citations for failing to
      accommodate resident needs or providing a clean, safe environment. The ratio of
      activities staff to residents is positively associated with QOL. This study did
      not find an association between QOL and either use of restraints or nurse staff
      levels. Approximately 9 percent of the total variance in self-reported QOL can be
      attributed to differences among facilities; 91 percent can be attributed to
      differences among residents. Resident level indicators explained about 4 percent
      of the variance attributable to differences among residents, and facility factors
      explained 49 percent of the variance attributable to differences among NFs.
      However, the different variables explained only 10 percent of the variance in
      self-reported QOL. IMPLICATIONS: A brief self-report measure of NF resident QOL
      is consistently associated with measures that can be constructed from extant data
      sources. However, the level of prediction possible from these data sources does
      not justify reliance on external indicators of resident QOL for policy purposes.

PMID- 16584453
TI  - Do physicians always flee from HMOs? New results using dynamic panel estimation
      methods.
AB  - OBJECTIVE: To assess the impact of changes in relative health maintenance
      organization (HMO) penetration on changes in the physician-to-population ratio in
      California counties when changes in the economic conditions in California
      counties relative to the U.S. average are taken into account. DATA SOURCES: Data
      on physicians who practiced in California at any time from 1988 to 1998 were
      obtained from the AMA Masterfile. The analysis was restricted to active, patient
      care physicians, excluding medical residents. Data on other covariates in the
      model were obtained from the Bureau of Economic Analysis, InterStudy, the Area
      Resource File, and the California state government. Data were merged using county
      FIPS codes. STUDY DESIGN: Changes in the physician-to-population ratio in
      California counties include the effects of both intrastate migration and
      interstate migration. A reduced-form model was estimated using the Arellano-Bond
      dynamic panel estimator. Economic conditions in California relative to the U.S.
      were measured as the ratio of county-level real per capita income to national
      level real per capita income. Relative HMO penetration in California was measured
      as the ratio of county-level HMO penetration to HMO penetration in the U.S.
      relative HMO penetration was instrumented using five identifying variables to
      address potential endogeneity. Omitted-variable bias was controlled for by first
      differencing the model. The model also incorporated eight other covariates that
      may be associated with the demand for physicians: the percentage of the
      population enrolled in Medicaid, beds in short-term hospitals per 100,000
      population, the percentage of the population that is black, the percentage of the
      population that is Hispanic, the percentage of the population that is Asian, the
      percentage of the population that is below age 18, the percentage of the
      population that is aged 65 and older, and the percentage of the population that
      are new legal immigrants in a given year. All of the above variables were lagged
      one period. The lagged physician-to-population ratio was also included to control
      for the supply of physicians. Separate equations were estimated for primary care
      physicians and specialist physicians. PRINCIPAL FINDINGS: Changes in lagged
      relative HMO penetration are negatively associated with changes in specialist
      physicians per 100,000 population. However, this effect of HMO penetration is
      attenuated and at times reversed in areas where the magnitude of the difference
      in relative economic conditions is sufficiently large. We did not find any
      statistically significant effects for primary care physicians. CONCLUSIONS:
      Consistent with prior studies, we find that changes in physician supply are
      associated with changes in relative HMO penetration. Relative economic conditions
      are an important moderator of the effect of changes in relative HMO penetration
      on physician migration.

PMID- 16584454
TI  - Variation in hospital length of stay: do physicians adapt their length of stay
      decisions to what is usual in the hospital where they work?
AB  - OBJECTIVE: To test the hypothesis that physicians who work in different hospitals
      adapt their length of stay decisions to what is usual in the hospital under
      consideration. DATA SOURCES: Secondary data were used, originating from the
      Statewide Planning and Research Cooperative System (SPARCS). SPARCS is a major
      management tool for assisting hospitals, agencies, and health care organizations
      with decision making in relation to financial planning and monitoring of
      inpatient and ambulatory surgery services and costs in New York state. STUDY
      DESIGN: Data on length of stay for surgical interventions and medical conditions
      (a total of seven diagnosis-related groups [DRGs]) were studied, to find out
      whether there is more variation between than within hospitals. Data (1999, 2000,
      and 2001) from all hospitals in New York state were used. The study examined
      physicians practicing in one hospital and physicians practicing in more than one
      hospital, to determine whether average length of stay differs according to the
      hospital of practice. Multilevel models were used to determine variation between
      and within hospitals. A t-test was used to test whether length of stay for
      patients of each multihospital physician differed from the average length of stay
      in each of the two hospitals. PRINCIPAL FINDINGS: There is significantly (p<.05)
      more variation between than within hospitals in most of the study populations.
      Physicians working in two hospitals had patient lengths of stay comparable with
      the usual practice in the hospital where the procedure was performed. The
      proportion of physicians working in one hospital did not have a consistent effect
      for all DRGs on the variation within hospitals. CONCLUSION: Physicians adapt to
      their colleagues or to the managerial demands of the particular hospital in which
      they work. The hospital and broader work environment should be taken into account
      when developing effective interventions to reduce variation in medical practice.

PMID- 16584455
TI  - Religious involvement and the use of mental health care.
AB  - OBJECTIVES: To examine the association between religious involvement and mental
      health care use by adults age 18 or older with mental health problems. METHODS:
      We used data from the 2001-2003 National Surveys on Drug Use and Health. We
      defined two subgroups with moderate (n=49,902) and serious mental or emotional
      distress (n=14,548). For each subgroup, we estimated a series of bivariate probit
      models of past year use of outpatient care and prescription medications using
      indicators of the frequency of religious service attendance and two measures of
      the strength and influence of religious beliefs as independent variables.
      Covariates included common Diagnostic and Statistical Manual of Mental Disorders,
      4th Edition, disorders symptoms, substance use and related disorders, self-rated
      health status, and sociodemographic characteristics. RESULTS: Among those with
      moderate distress, we found some evidence of a positive relationship between
      religious service attendance and outpatient mental health care use and of a
      negative relationship between the importance of religious beliefs and outpatient
      use. Among those with serious distress, use of outpatient care and medication was
      more strongly associated with service attendance and with the importance of
      religious beliefs. By contrast, we found a negative association between
      outpatient use and the influence of religious beliefs on decisions. CONCLUSION:
      The positive relationship between religious service participation and service use
      for those with serious distress suggests that policy initiatives aimed at
      increasing the timely and appropriate use of mental health care may be able to
      build upon structures and referral processes that currently exist in many
      religious organizations.

PMID- 16584457
TI  - Health insurance and health at age 65: implications for medical care spending on
      new Medicare beneficiaries.
AB  - OBJECTIVES: To investigate the consequences of endogeneity bias on the estimated
      effect of having health insurance on health at age 63 or 64, just before most
      people qualify for Medicare, and to simulate the implications for total and
      public insurance (Medicare and Medicaid) spending on newly enrolled beneficiaries
      in their first years of Medicare coverage. DATA: The longitudinal Health and
      Retirement Survey of people who were 55-61 years old in 1992, followed through
      biannual surveys to age 63-64 or until 2000 (whichever came first), and those who
      were 66-70 years olds from the Medicare Current Beneficiary Surveys, 1992-1998.
      STUDY DESIGN: Instrumental variable (IV) estimation of a simultaneous equation
      model of insurance choice and health at age 63-64 as a function of baseline
      health and sociodemographic characteristics in 1992 and endogenous insurance
      coverage over the observation period. FINDINGS: Continuous insurance coverage is
      associated with significantly fewer deaths prior to age 65 and, among those who
      survive, a significant upward shift in the distribution of health states from
      fair and poor health with disabilities to good to excellent health. Treating
      insurance coverage as endogenous increases the magnitude of the estimated effect
      of having insurance on improved health prior to age 65. The medical spending
      simulations suggest that if the near-elderly had continuous insurance coverage,
      average annual medical spending per capita for new Medicare beneficiaries in
      their first few years of coverage would be slightly lower because of the
      improvement in health status. In addition, total Medicare and Medicaid spending
      for new beneficiaries over their first few years of coverage would be about the
      same or slightly lower, even though more people survive to age 65. CONCLUSIONS:
      Extending insurance coverage to all Americans between the ages of 55 and 64 would
      improve health (increase survival and shift people from good-fair-poor health to
      excellent-very good health) at age 65, and possibly reduce total short-term
      spending by Medicare and Medicaid for newly eligible Medicare beneficiaries, even
      though more people would enter the program because of increased survival.

PMID- 16584456
TI  - Prescription drug expenditures and population demographics.
AB  - OBJECTIVE: To provide detailed demographic profiles of prescription drug
      utilization and expenditures in order to isolate the impact of demographic change
      from other factors that affect drug expenditure trends. DATA SOURCES/STUDY
      SETTING: Demographic information and drug utilization data were extracted for
      virtually the entire British Columbia (BC) population of 1996 and 2002. All
      residents had public medical and hospital insurance; however their drug coverage
      resembled the mix of private and public insurance in the United States. STUDY
      DESIGN: A series of research variables were constructed to illustrate profiles of
      drug expenditures and drug utilization across 96 age/sex strata. DATA
      COLLECTION/EXTRACTION METHODS: Drug use and expenditure information was extracted
      from the BC PharmaNet, a computer network connecting all pharmacies in the
      province. PRINCIPAL FINDINGS: Per capita drug expenditures increased at an
      average annual rate of 10.8 percent between 1996 and 2002. Population aging
      explained 1.0 points of this annual rate of expenditure growth; the balance was
      attributable to rising age/sex-specific drug expenditures. CONCLUSIONS:
      Relatively little of the observed increase in drug expenditures in BC could be
      attributed to demographic change. Most of the expenditure increase stemmed from
      the age/sex-specific quantity and type of drugs purchased. The sustainability of
      drug spending therefore depends not on outside forces but on decisions made by
      policy makers, prescribers, and patients.

PMID- 16584458
TI  - Commentary--sophisticated methods but implausible results: how much does health
      insurance improve health?

PMID- 16584460
TI  - The effect of rural hospital closures on community economic health.
AB  - OBJECTIVE: To examine the effect of rural hospital closures on the local economy.
      DATA SOURCES: U.S. Census Bureau, OSCAR, Medicare Cost Reports, and surveys of
      individuals knowledgeable about local hospital closures. STUDY DESIGN: Economic
      data at the county level for 1990-2000 were combined with information on hospital
      closures. The study sample was restricted to rural counties experiencing a
      closure during the sample period. Longitudinal regression methods were used to
      estimate the effect of hospital closure on per-capita income, unemployment rate,
      and other community economic measures. Models included both leading and lagged
      closure terms allowing a preclosure economic downturn as well as time for the
      closure to be fully realized by the community. DATA COLLECTION: Information on
      closures was collected by contacting every state hospital association,
      reconciling information gathered with that contained in the American Hospital
      Association file and OIG reports. PRINCIPAL FINDINGS: Results indicate that the
      closure of the sole hospital in the community reduces per-capita income by 703
      dollars (p<0.05) or 4 percent (p<0.05) and increases the unemployment rate by 1.6
      percentage points (p<0.01). Closures in communities with alternative sources of
      hospital care had no long-term economic impact, although income decreased for 2
      years following the closure. CONCLUSIONS: The local economic effects of a
      hospital closure should be considered when regulations that affect hospitals'
      financial well-being are designed or changed.

PMID- 16584461
TI  - How did welfare reform affect the health insurance coverage of women and
      children?
AB  - OBJECTIVE: To measure the change in U.S. women and children's health insurance
      coverage as a result of welfare reform (i.e. the creation of Temporary Assistance
      for Needy Families or TANF) in 1996. DATA SOURCE: 1992-1999 longitudinal data
      from the Survey of Income and Program Participation (SIPP) merged with data on
      the timing of state implementation of welfare reform after 1996. Two key
      advantages of the SIPP data are that they permit matching type of insurance
      coverage to the welfare policy environment in each state in each month, and
      permit controlling for individual-level fixed effects. STUDY DESIGN: We measure
      how much insurance coverage changed after welfare reform using a difference in
      differences method that eliminates the influence of time-invariant unobserved
      individual heterogeneity and of statewide trends in insurance coverage. Models
      also control for individual, state, and year fixed effects, individual-level
      characteristics such as education, age, and number of children, plus state-level
      variables such as real per capita income, real minimum wage, and Medicaid
      eligibility. DATA COLLECTION/EXTRACTION METHODS: We limit our analysis to the
      SIPP data specific to the month just completed prior to the interview; as a
      result, we have up to twelve observations for each individual in the SIPP. This
      paper uses pooled data from the 1992-1996 panels of the SIPP covering the period
      1992-1999. Publicly available state identifiers permit the merger of state
      policies and macroeconomic variables with the SIPP. PRINCIPAL FINDINGS: TANF
      implementation is associated with an 8.1 percent increase in the probability that
      a welfare-eligible woman was uninsured. Welfare reform had less of an impact on
      the health insurance coverage of children. For example, TANF implementation was
      associated with a 3.0 percent increase in the probability that a welfare-eligible
      child lacked health insurance. CONCLUSIONS: An unintended consequence of welfare
      reform was to adversely impact the health insurance coverage of economically
      vulnerable women and children, and that this impact was several times larger than
      the previous literature implies.

PMID- 16584462
TI  - Disparities in primary care for vulnerable children: the influence of multiple
      risk factors.
AB  - OBJECTIVES: To analyze vulnerability as a profile of multiple risk factors for
      poor pediatric care based on race/ethnicity, poverty status, parent education,
      insurance, and language. Profiles are used to examine disparities in
      child/adolescent health status and primary care experience. DATA SOURCES: Cross
      sectional data on 19,485 children/adolescents 0-19 years of age from the 2001
      California Health Interview Survey. STUDY DESIGN: Multiple logistic regression
      models are used to examine risk profiles in relation to health status and three
      aspects of primary care: access (physician and dental visit; access surety),
      continuity (regular source of care), and comprehensiveness (i.e., health
      promotion counseling). PRINCIPAL FINDINGS: About 43 percent of (or 4.4 million)
      children in California have two or more risk factors (RF). Controlling for age
      and gender, more RFs is associated with poorer health status (i.e. percent
      reporting "excellent/very good" health: no RFs=81 percent, 1=71 percent, 2=57
      percent, 3=45 percent, 4=35 percent, 5=28 percent, all p<.001). Controlling for
      health status, higher risk profiles is associated with poorer primary care access
      and continuity, but greater comprehensiveness of care. For example, higher risk
      profile children are less likely to have a regular source of care: one RF
      (prevalence ratio [PR]=0.92, confidence interval [CI]: 0.86-0.98), two (PR=0.77,
      CI: 0.69-0.84), three (PR=0.55, CI: 0.46-0.65), and four or more (PR=0.31, CI:
      0.22-0.44), all p<.001. CONCLUSIONS: This study demonstrates a dose-response
      relationship of higher risk profiles with poorer child health status, access to,
      and continuity of primary care. Having gained access, however, adolescents with
      higher risk profiles are more likely to receive health promotion counseling.
      Higher profiles appear to be associated with greater barriers to accessing
      primary care for children in "fair or poor" health, suggesting that vulnerable
      children who have the greatest health care needs also have the greatest
      difficulty obtaining primary care.

PMID- 16584463
TI  - Disparities in the reporting and treatment of health conditions in children: an
      analysis of the Medical Expenditure Panel Survey.
AB  - OBJECTIVES: To determine whether racial and ethnic disparities in health care use
      differ for physical and behavioral health conditions. DATA SOURCES: Secondary
      analysis of the 1996-1997 Medical Expenditure Panel Survey. STUDY DESIGN:
      Retrospective cohort study of children aged 2-18 years old who were members of
      participating households. Children were categorized as Hispanic, black, or white.
      Differences in caregiver-reported behavioral and physical health conditions and
      services use were compared, and estimates were weighted to reflect the complex
      sampling scheme. PRINCIPAL FINDINGS: Of eligible children weighted to represent
      over 44 million in each year, 13-15 percent were Hispanic, 14 percent black, and
      68-70 percent white. After adjusting for potential confounding, Hispanic and
      black children were less likely to report externalizing behavioral conditions
      than white children. Black but not Hispanic children were more likely than white
      children to report asthma. In addition, Hispanic and black children were less
      likely to report ambulatory visits, and black children were less likely to report
      receiving a prescription medication than white children. There were no
      differences in reported emergency room visits or hospitalizations. Interactions
      between race and various health conditions, health status, insurance, and income
      were not significant. CONCLUSIONS: In this nationally representative sample, we
      identified racial and ethnic disparities in the reporting of health conditions
      and the use of discretionary health services. Disparities differed between those
      with behavioral conditions and those with physical conditions. These disparities
      were not explained by traditional measures including the presence of health
      conditions, health status, insurance, and family income, and suggest that
      national surveys such as Medical Expenditure Panel Survey may benefit from the
      inclusion of additional explanatory measures.

PMID- 16584464
TI  - Application of regression-discontinuity analysis in pharmaceutical health
      services research.
AB  - OBJECTIVE: To demonstrate how a relatively underused design, regression
      discontinuity (RD), can provide robust estimates of intervention effects when
      stronger designs are impossible to implement. DATA SOURCES/STUDY SETTING:
      Administrative claims from a Mid-Atlantic state Medicaid program were used to
      evaluate the effectiveness of an educational drug utilization review
      intervention. STUDY DESIGN: Quasi-experimental design. DATA COLLECTION/EXTRACTION
      METHODS: A drug utilization review study was conducted to evaluate a letter
      intervention to physicians treating Medicaid children with potentially excessive
      use of short-acting beta(2)-agonist inhalers (SAB). The outcome measure is change
      in seasonally-adjusted SAB use 5 months pre- and postintervention. To determine
      if the intervention reduced monthly SAB utilization, results from an RD analysis
      are compared to findings from a pretest-posttest design using repeated-measure
      ANOVA. PRINCIPAL FINDINGS: Both analyses indicated that the intervention
      significantly reduced SAB use among the high users. Average monthly SAB use
      declined by 0.9 canisters per month (p<.001) according to the repeated-measure
      ANOVA and by 0.2 canisters per month (p<.001) from RD analysis. CONCLUSIONS:
      Regression-discontinuity design is a useful quasi-experimental methodology that
      has significant advantages in internal validity compared to other pre-post
      designs when assessing interventions in which subjects' assignment is based on
      cutoff scores for a critical variable.

PMID- 16584466
TI  - Should episode-based economic profiles be risk adjusted to account for
      differences in patients' health risks?
AB  - OBJECTIVE: To determine whether additional risk adjustment is necessary in
      economic profiling of physicians when claims data are already grouped into
      episodes of care, and to measure effects of risk adjustment on cost efficiency
      rankings of physicians. DATA SOURCES: Four years of inpatient, outpatient,
      professional, and pharmacy claims data from a mixed model HMO. STUDY DESIGN:
      Claims data were processed through Symmetry Health Data Systems' episode
      treatment group (ETG) grouper to define episodes of care and Symmetry's episode
      risk group (ERG) software to define measures of patients' health risk scores. For
      each episode type (ETG), ETG-mean expected costs were calculated as the mean
      costs of all episodes of that type, and risk-adjusted expected costs were
      calculated using three alternative risk model formulations. DATA COLLECTION:
      Within specialties, physicians were ranked from most cost efficient to least cost
      efficient, based on standardized difference between actual and expected costs.
      ETG-mean based rankings were compared with risk-adjusted rankings. Analyses were
      performed for cardiologists, family practitioners, general surgeons, and
      neurologists. PRINCIPAL FINDINGS: With all three risk models, risk scores were
      essentially unrelated to episode costs in approximately three-fourths of episode
      categories (ETGs). In a sample of ETGs for which risks-costs relationships
      appeared to exist, split sample validation showed the relationships to be
      unstable or spurious in all except one ETG. Within specialties, risk-adjusted
      cost efficiency rankings differ little from ETG-mean adjusted rankings.
      CONCLUSIONS: Depending upon the purpose for which economic profiling is
      performed, additional risk adjustment, beyond that already provided by episode
      grouping, may be unnecessary. Additional research may be needed to identify and
      validate ETG-level relationships between patient risks and episode costs.

PMID- 16584465
TI  - Failure of ICD-9-CM codes to identify patients with comorbid chronic kidney
      disease in diabetes.
AB  - OBJECTIVE: To determine prevalence of chronic kidney disease (CKD) in patients
      with diabetes, and accuracy of International Classification of Diseases, 9th
      Revision, Clinical Modification (ICD-9-CM) codes to identify such patients. DATA
      SOURCES/STUDY SETTING: Secondary data from 1999 to 2000. We linked all inpatient
      and outpatient administrative and clinical records of U.S. veterans with diabetes
      dually enrolled in Medicare and the Veterans Administration (VA) health care
      systems. STUDY DESIGN: We used a cross-sectional, observational design to
      determine the sensitivity and specificity of renal-related ICD-9-CM diagnosis
      codes in identifying individuals with chronic kidney disease. DATA
      COLLECTION/EXTRACTION METHODS: We estimated glomerular filtration rate (eGFR)
      from serum creatinine and defined CKD as Stage 3, 4, or 5 CKD by eGFR criterion
      according to the Kidney Disease Outcomes Quality Initiative guidelines. Renal
      related ICD-9-CM codes were grouped by algorithm. PRINCIPAL FINDINGS: Prevalence
      of CKD was 31.6 percent in the veteran sample with diabetes. Depending on the
      detail of the algorithm, only 20.2 to 42.4 percent of individuals with CKD
      received a renal-related diagnosis code in either VA or Medicare records over 1
      year. Specificity of renal codes for CKD ranged from 93.2 to 99.4 percent.
      Patients hospitalized in VA facilities were slightly more likely to be correctly
      coded for CKD than patients hospitalized in facilities reimbursed by Medicare (OR
      5.4 versus 4.1, p=.0330) CONCLUSIONS: CKD is a common comorbidity for patients
      with diabetes in the VA system. Diagnosis codes in administrative records from
      Medicare and VA systems are insensitive, but specific markers for patients with
      CKD.

PMID- 16584467
TI  - Patient turnover and nursing staff adequacy.
AB  - OBJECTIVE: To assess the relative validity of patient turnover adjustments and
      the difference in nurse staffing using measures that adjust for patient turnover
      and severity versus those that do not. DATA SOURCES: Numbers of registered nurses
      (RNs), adjusted patient days of care (APDC), length of stay, and patient severity
      information from acute care general hospitals in Pennsylvania 1994-2001, obtained
      from the Pennsylvania Department of Health, the American Hospital Association,
      and the Atlas MediQual system. STUDY DESIGN: After examining the trends in
      patient turnover and severity and their relationship to RN staffing, we apply two
      patient turnover indices, with and without patient severity adjustments, to RN
      staffing measures, and test the difference between the original and adjusted
      measures using paired sample t-tests. DATA EXTRACTION METHODS: Data sets were
      match merged by hospital ID, and patient turnover and severity indices were
      created, using 1994 as the base year. RN staffing measures were developed using
      unadjusted APDC, and APDC adjusted for patient turnover and both patient turnover
      and severity. PRINCIPAL FINDINGS: Patient turnover increased significantly from
      1994 to 2001. The difference between RN staffing measures adjusted for patient
      turnover and severity and those not adjusted was increasingly significant from
      1995 onward. Unadjusted RN staffing showed a 1 percent decline over the 8-year
      period compared with decreases of from 9 to 26 percent after adjustments.
      CONCLUSIONS: These results indicate that the assessment of unadjusted RN staffing
      by RN to patient ratios alone underestimates nursing workload and overstates RN
      staffing levels. Patient turnover, as well as severity, should be taken into
      account in staffing assessment and decision making.

PMID- 16584469
TI  - The minimal genome keeps growing.

PMID- 16584470
TI  - Microbiological investigation of methane- and hydrocarbon-discharging mud
      volcanoes in the Carpathian Mountains, Romania.
AB  - Paclele Mici is a terrestrial mud volcano field located in the Carpathian
      Mountains (Romania), where thermal alteration of sedimentary organic compounds
      leads to methane, higher hydrocarbons and other petroleum compounds that are
      continuously released into the environment. The hydrocarbons represent potential
      substrates for microorganisms. We studied lipid biomarkers, stable isotope
      ratios, the effect of substrate (methane, other organic compounds) addition and
      16S rRNA genes to gain insights into the hitherto unknown microbial community at
      this site. Quantitative real-time polymerase chain reaction analysis demonstrated
      that bacteria were much more abundant than archaea. Phylogenetic analyses of 16S
      rDNA clone sequences indicated the presence of bacterial and archaeal lineages
      generally associated with the methane cycle (methanogens, aerobic and anaerobic
      methanotrophs), the sulfur cycle (sulfate reducers), and groups linked to the
      anaerobic degradation of alkanes or aromatic hydrocarbons. The presence of
      sulfate reducers, methanogens and methanotrophs in this habitat was also
      confirmed by concurrent surveys of lipid biomarkers and their isotopic
      signatures. Incubation experiments with several common and complex substrates
      revealed the potential of the indigenous microbial community for sulfate
      reduction, methanogenesis and aerobic methanotrophy. Additionally, consistently
      to the detection of methane-oxidizing archaea (ANME) and 13C-depleted archaeal
      lipids, a weak but significant activity of anaerobic methane oxidation was
      measured by radiotracer techniques and in vitro. This survey is the first to
      report the presence and activity of ANME in a terrestrial environment.

PMID- 16584472
TI  - Improved serial analysis of V1 ribosomal sequence tags (SARST-V1) provides a
      rapid, comprehensive, sequence-based characterization of bacterial diversity and
      community composition.
AB  - Serial analysis of ribosomal sequence tags (SARST) is a recently developed
      technology that can generate large 16S rRNA gene (rrs) sequence data sets from
      microbiomes, but there are numerous enzymatic and purification steps required to
      construct the ribosomal sequence tag (RST) clone libraries. We report here an
      improved SARST method, which still targets the V1 hypervariable region of rrs
      genes, but reduces the number of enzymes, oligonucleotides, reagents, and
      technical steps needed to produce the RST clone libraries. The new method,
      hereafter referred to as SARST-V1, was used to examine the eubacterial diversity
      present in community DNA recovered from the microbiome resident in the ovine
      rumen. The 190 sequenced clones contained 1055 RSTs and no less than 236 unique
      phylotypes (based on > or = 95% sequence identity) that were assigned to eight
      different eubacterial phyla. Rarefaction and monomolecular curve analyses
      predicted that the complete RST clone library contains 99% of the 353 unique
      phylotypes predicted to exist in this microbiome. When compared with ribosomal
      intergenic spacer analysis (RISA) of the same community DNA sample, as well as a
      compilation of nine previously published conventional rrs clone libraries
      prepared from the same type of samples, the RST clone library provided a more
      comprehensive characterization of the eubacterial diversity present in rumen
      microbiomes. As such, SARST-V1 should be a useful tool applicable to
      comprehensive examination of diversity and composition in microbiomes and offers
      an affordable, sequence-based method for diversity analysis.

PMID- 16584471
TI  - The m-xylene biodegradation capacity of Pseudomonas putida mt-2 is submitted to
      adaptation to abiotic stresses: evidence from expression profiling of xyl genes.
AB  - The effect of archetypal environmental stresses on expression of the catabolic
      xyl genes of the TOL plasmid pWW0 of the m-xylene degrading strain Pseudomonas
      putida mt-2 has been investigated. To this end, a subgenomic DNA chip was
      employed which included structural and regulatory DNA sequences of the TOL
      pathway along with selected descriptors of specific physiological conditions.
      Cells were separately exposed to m-xylene under various oxygen tensions,
      temperatures and nitrogen sources as well as situations of DNA damage, oxidative
      stress, carbon and iron starvation, respiratory chain damage, and contact with
      arsenic, but at doses which did not cause a gross effect on growth or cell
      viability. The incidence of each stress class was categorized through the
      corresponding descriptors in the chip in respect to the relative output of xyl
      transcripts. While most of the stresses downregulated the m-xylene biodegradation
      related genes, some uncouplers of the respiratory chain (azide) and small doses
      of arsenate appeared to stimulate their expression. The replacement of NH4+ by
      NO3- as N source augmented expression of the TOL cistrons also. We subsequently
      subjected P. putida mt-2 cells to the multiple abiotic stress brought about by
      exposure to crude tar from the 2002 oil spill of the Prestige tanker, which
      embraces a complex mixture of hydrocarbons. The resulting expression profile of
      xyl genes and stress-responding markers over time suggested that adaptation to
      external insults precedes any significant expression of the catabolic genes. The
      consequences of this hierarchy of responses for microbial biodegradation in situ
      are discussed.

PMID- 16584473
TI  - Analysis of the first genome fragment from the marine sponge-associated, novel
      candidate phylum Poribacteria by environmental genomics.
AB  - The novel candidate phylum Poribacteria is specifically associated with several
      marine demosponge genera. Because no representatives of Poribacteria have been
      cultivated, an environmental genomic approach was used to gain insights into
      genomic properties and possibly physiological/functional features of this elusive
      candidate division. In a large-insert library harbouring an estimated 1.1 Gb of
      microbial community DNA from Aplysina aerophoba, a Poribacteria-positive 16S rRNA
      gene locus was identified. Sequencing and sequence annotation of the 39 kb size
      insert revealed 27 open reading frames (ORFs) and two genes for stable RNAs. The
      fragment exhibited an overall G+C content of 50.5% and a coding density of 86.1%.
      The 16S rRNA gene was unlinked from a conventional rrn operon. Its flanking
      regions did not show any synteny to other 16S rRNA encoding loci from
      microorganisms with unlinked rrn operons. Two of the predicted hypothetical
      proteins were highly similar to homologues from Rhodopirellula baltica.
      Furthermore, a novel kind of molybdenum containing oxidoreductase was predicted
      as well as a series of eight ORFs encoding for unusual transporters, channel or
      pore forming proteins. This environmental genomics approach provides, for the
      first time, genomic and, by inference, functional information on the so far
      uncultivated, sponge-associated candidate division Poribacteria.

PMID- 16584474
TI  - Replicability of dominant bacterial populations after long-term surfactant
      enrichment in lab-scale activated sludge.
AB  - Bacterial communities were examined in replicate lab-scale activated sludge
      reactors after a period of several months of enrichment with non-ionic
      nonylphenol ethoxylate (NPE) surfactants. Four sequential batch reactors were fed
      with synthetic sewage, two of which received additionally NPE. Small subunit rDNA
      derived denaturing gel gradient electrophoresis (DGGE) profiles and 16S rDNA
      clone libraries were dominated by clones of Gammaproteobacteria class. Sequences
      of the other codominant rDNA phylotypes observed only in DGGE from NPE-amended
      reactors were, respectively, associated with the Group III of the Acidobacteria
      phylum. Intriguingly, 16S rRNA content from abundant Gammaproteobacteria cells
      was unexpectedly low. In addition to Acidobacteria, rRNA-derived DGGE profiles
      were dominated by members of the order Burkholderiales (of the
      Betaproteobacteria) and of the genus Sphingomonas (a member of the
      Alphaproteobacteria). Specific oligonucleotide probes for the selected ribotypes
      were designed and applied for quantitative real time polymerase chain reaction
      and fluorescence in situ hybridization, confirming their dominance in treated
      reactors. The parallel abundance of unique phylotypes in replicate reactors
      implies a distinctive selection of dominant organisms, which are better adapted
      to specialized niches in the highly selective environment.

PMID- 16584475
TI  - A two-partner secretion system is involved in seed and root colonization and iron
      uptake by Pseudomonas putida KT2440.
AB  - We describe the first two-partner secretion system known to play a role in
      mutualistic plant-bacterial interactions, identified in the soil and rhizosphere
      colonizing bacterium Pseudomonas putida KT2440. The genes coding for the two
      components of the system are organized in an operon, which we have named hlpBA.
      HlpA is a secreted protein that has similarities with iron-regulated haemolysins,
      while HlpB would be responsible for the activation and transport of HlpA across
      the outer membrane. Mutations in this novel two-partner secretion system result
      in reduced capacity to colonize corn seeds. When introduced in the rhizosphere,
      hlpA and hlpB mutants show no competitive disadvantage, but the number of cells
      attached to the root surface is reduced with respect to the wild type, suggesting
      this protein plays a role directly in the bacterial cell-root surface
      interaction. Under iron-limiting conditions, the presence of a truncated HlpA
      causes reduced viability and high levels of siderophore release. These data
      further strengthen our previous observations indicating the importance of iron
      acquisition for attachment of P. putida KT2440 to plant surfaces.

PMID- 16584476
TI  - Membrane lipids of mesophilic anaerobic bacteria thriving in peats have typical
      archaeal traits.
AB  - The 16S ribosomal DNA based distinction between the bacterial and archaeal
      domains of life is strongly supported by the membrane lipid composition of the
      two domains; Bacteria generally contain dialkyl glycerol diester lipids, whereas
      Archaea produce isoprenoid dialkyl glycerol diether and membrane-spanning
      glycerol dialkyl glycerol tetraether (GDGT) lipids. Here we show that a new group
      of ecologically abundant membrane-spanning GDGT lipids, containing branched
      instead of isoprenoid carbon skeletons, are of a bacterial origin. This was
      revealed by examining the stereochemistry of the glycerol moieties of those
      branched tetraether membrane lipids, which was found to be the bacterial 1,2-di-O
      alkyl-sn-glycerol stereoconfiguration and not the 2,3-di-O-alkyl-sn-glycerol
      stereoconfiguration as in archaeal membrane lipids. In addition, unequivocal
      evidence for the presence of cyclopentyl moieties in these bacterial membrane
      lipids was obtained by NMR. The biochemical traits of biosynthesis of tetraether
      membrane lipids and the formation of cyclopentyl moieties through internal
      cyclization, which were thought to be specific for the archaeal lineage of
      descent, thus also occur in the bacterial domain of life.

PMID- 16584477
TI  - Quantitative reverse transcription polymerase chain reaction analysis of Vibrio
      cholerae cells entering the viable but non-culturable state and starvation in
      response to cold shock.
AB  - We performed a comparative analysis of the Vibrio cholerae strain El Tor 3083
      entering the viable but non-culturable (VBNC) state and starvation after
      incubation in artificial seawater (ASW) at 4 and 15 degrees C respectively. To
      this end, we determined bacterial culturability and membrane integrity, as well
      as the cellular levels of 16S rRNA and mRNA for the tuf, rpoS and relA genes,
      which were assessed by real-time quantitative reverse transcription polymerase
      chain reaction (Q-RT-PCR). Bacterial cells entering the VBNC state showed a 154,
      5.1 x 10(3), 24- and 23-fold reduction in the number of copies of 16S rRNA and
      mRNA for tuf, rpoS and relA, in comparison to exponentially growing cells. The
      differences were less striking between cells in the VBNC and starvation states.
      The mRNA for relA was selectively increased in VBNC cells (3.2-folds), whereas a
      3.9-fold reduction was observed for 16S rRNA. The obtained results confirmed that
      key activities of the cellular metabolism (i.e. tuf representing protein
      synthesis, and relA or rpoS stress response) were still detected in bacteria
      entering the VBNC state and starvation. These data suggest that the new Q-RT-PCR
      methodology, based on the selected RNA targets, could be successfully exploited
      for the identification (rRNA) of V. cholerae and assessment of its metabolic
      activity (tuf, rpoS, relA mRNA) in environmental samples.

PMID- 16584478
TI  - Vancomycin- and erythromycin-resistant enterococci in a pig farm and its
      environment.
AB  - A high prevalence of vancomycin- and erythromycin-resistant enterococci (VRE and
      ERE respectively) in a pig farm and its environment was observed. A similar
      structure and composition of enterococcal populations was detected between urban
      sewage and those associated with the pig environment. Enterococcus faecium was
      the most predominant species among VRE isolates from both animal and human
      origin. The high population similarity index (Sp) obtained comparing VRE and ERE
      isolates from urban sewage and pig slurry suggests that there are certain strains
      circulating through the food chain from farms to humans. Erythromycin resistance
      was present in a wider variety of clones and species of enterococci in both pigs
      and humans than vancomycin resistance.

PMID- 16584479
TI  - Vibrio parahaemolyticus in shellfish and clinical samples during two large
      epidemics of diarrhoea in southern Chile.
AB  - Large epidemics of diarrhoea associated with seafood consumption and Vibrio
      parahaemolyticus occurred during the austral summers of 2004 and 2005 in the
      environs of Puerto Montt, Chile (41 degrees 29'S 72 degrees 24'W). There are no
      reports of V. parahaemolyticus infections before 2004 in this region, their
      absence being explained by the low ocean temperatures which seldom reach 16
      degrees C. We analysed V. parahaemolyticus obtained from shellfish and clinical
      samples during epidemics. Isolates were examined using conventional protocols and
      an improved method for restriction enzyme analysis using total bacterial DNA
      which permits direct genome restriction enzyme analysis by conventional gel
      electrophoresis (DGREA) with a similar discrimination index as restriction
      fragment length polymorphism-pulsed field gel electrophoresis (RFLP-PFGE).
      Analysis of clinical samples showed that the epidemics were caused by the V.
      parahaemolyticus O3:K6 pandemic clonal group. On the other hand, analysis of
      shellfish samples during both epidemics showed that 53% contained V.
      parahaemolyticus (3-93 g(-1)). Detailed analysis of 50 positive shellfish samples
      showed that only three contained detectable levels of the pandemic clone. Most V.
      parahaemolyticus isolates obtained from shellfish corresponded to non-pandemic
      clones differentiated into 14 groups by DGREA. In summary, the causative agent
      during epidemics was only a minor component of a small but diverse population of
      V. parahaemolyticus in shellfish.

PMID- 16584480
TI  - Changes in the community structure and activity of betaproteobacterial ammonia
      oxidizing sediment bacteria along a freshwater-marine gradient.
AB  - To determine whether the distribution of estuarine ammonia-oxidizing bacteria
      (AOB) was influenced by salinity, the community structure of betaproteobacterial
      ammonia oxidizers (AOB) was characterized along a salinity gradient in sediments
      of the Ythan estuary, on the east coast of Scotland, UK, by denaturant gradient
      gel electrophoresis (DGGE), cloning and sequencing of 16S rRNA gene fragments.
      Ammonia-oxidizing bacteria communities at sampling sites with strongest marine
      influence were dominated by Nitrosospira cluster 1-like sequences and those with
      strongest freshwater influence were dominated by Nitrosomonas oligotropha-like
      sequences. Nitrosomonas sp. Nm143 was the prevailing sequence type in communities
      at intermediate brackish sites. Diversity indices of AOB communities were similar
      at marine- and freshwater-influenced sites and did not indicate lower species
      diversity at intermediate brackish sites. The presence of sequences highly
      similar to the halophilic Nitrosomonas marina and the freshwater strain
      Nitrosomonas oligotropha at identical sampling sites indicates that AOB
      communities in the estuary are adapted to a range of salinities, while individual
      strains may be active at different salinities. Ammonia-oxidizing bacteria
      communities that were dominated by Nitrosospira cluster 1 sequence types, for
      which no cultured representative exists, were subjected to stable isotope probing
      (SIP) with 13C-HCO3-, to label the nucleic acids of active autotrophic
      nitrifiers. Analysis of 13C-associated 16S rRNA gene fragments, following CsCl
      density centrifugation, by cloning and DGGE indicated sequences highly similar to
      the AOB Nitrosomonas sp. Nm143 and Nitrosomonas cryotolerans and to the nitrite
      oxidizer Nitrospira marina. No sequence with similarity to the Nitrosospira
      cluster 1 clade was recovered during SIP analysis. The potential role of
      Nitrosospira cluster 1 in autotrophic ammonia oxidation therefore remains
      uncertain.

PMID- 16584481
TI  - A new green fluorescent protein-based bacterial biosensor for analysing
      phenanthrene fluxes.
AB  - The polycyclic aromatic hydrocarbon (PAH)-degrading strain Burkholderia sp. RP007
      served as host strain for the design of a bacterial biosensor for the detection
      of phenanthrene. RP007 was transformed with a reporter plasmid containing a
      transcriptional fusion between the phnS putative promoter/operator region and the
      gene encoding the enhanced green fluorescent protein (GFP). The resulting
      bacterial biosensor--Burkholderia sp. strain RP037--produced significant amounts
      of GFP after batch incubation in the presence of phenanthrene crystals. Co
      incubation with acetate did not disturb the phenanthrene-specific response but
      resulted in a homogenously responding population of cells. Active metabolism was
      required for induction with phenanthrene. The magnitude of GFP induction was
      influenced by physical parameters affecting the phenanthrene flux to the cells,
      such as the contact surface area between solid phenanthrene and the aqueous
      phase, addition of surfactant, and slow phenanthrene release from Model Polymer
      Release System beads or from a water-immiscible oil. These results strongly
      suggest that the bacterial biosensor can sense different phenanthrene fluxes
      while maintaining phenanthrene metabolism, thus acting as a genuine sensor for
      phenanthrene bioavailability. A relationship between GFP production and
      phenanthrene mass transfer is proposed.

PMID- 16584482
TI  - Deep biosphere-related bacteria within the subsurface of tidal flat sediments.
AB  - Biogeochemical and microbiological processes in the upper sediment layers of
      tidal flats were analysed in many investigations, while deeper zones remained
      largely unexplored. Therefore, denaturant gradient gel electrophoresis (DGGE)
      analysis of 16S rRNA gene fragments along the depth profile of up to 5.5 m-long
      sediment cores was performed in comparison with lithological and geochemical
      parameters. The investigation revealed that different compartments of the
      sediment columns were characterized by specific microbial communities. These
      compartments were analysed by sequencing of 113 DGGE bands. The upper layers down
      to 160-200 cm were dominated by gamma- and delta-Proteobacteria representing more
      than 60% of the total number of phylotypes. Underneath, a striking shift in
      community composition was observed, as the Proteobacteria were replaced by
      Chloroflexi with more than 60% of all sequences. As sulfate was still available
      as an electron acceptor in these layers, the abundance of Chloroflexi might be
      promoted by the electron donor or the quality of the carbon source. The dominance
      of this group, previously known as green non-sulfur bacteria, indicates the
      presence of a typical deep-biosphere microbial community in relatively young
      subsurface sediments. Thus, tidal flats might offer a convenient possibility to
      study and understand certain aspects of the deep biosphere in general.

PMID- 16584483
TI  - Denaturing gradient electrophoresis (DGE) and single-strand conformation
      polymorphism (SSCP) molecular fingerprintings revisited by simulation and used as
      a tool to measure microbial diversity.
AB  - The exact extent of microbial diversity remains unknowable. Nevertheless,
      fingerprinting patterns [denaturing gradient electrophoresis (DGE), single-strand
      conformation polymorphism (SSCP)] provide an image of a microbial ecosystem and
      contain diversity data. We generated numerical simulation fingerprinting patterns
      based on three types of distribution (uniform, geometric and lognormal) with a
      range of units from 10 to 500,000. First, simulated patterns containing a
      diversity of around 1000 units or more gave patterns similar to those obtained in
      experiments. Second, the number of bands or peaks saturated quickly to about 35
      and were unrelated to the degree of diversity. Finally, assuming lognormal
      distribution, we used an estimator of diversity on in silico and experimental
      fingerprinting patterns. Results on in silico patterns corresponded to the
      simulation inputs. Diversity results in experimental patterns were in the same
      range as those obtained from the same DNA sample in molecular inventories. Thus,
      fingerprinting patterns contain extractable data about diversity although not on
      the basis of a number of bands or peaks, as is generally assumed to be the case.

PMID- 16584484
TI  - Quantifying the roles of immigration and chance in shaping prokaryote community
      structure.
AB  - Naturally occurring populations of bacteria and archaea are vital to life on the
      earth and are of enormous practical significance in medicine, engineering and
      agriculture. However, the rules governing the formation of such communities are
      still poorly understood, and there is a need for a usable mathematical
      description of this process. Typically, microbial community structure is thought
      to be shaped mainly by deterministic factors such as competition and niche
      differentiation. Here we show, for a wide range of prokaryotic communities, that
      the relative abundance and frequency with which different taxa are observed in
      samples can be explained by a neutral community model (NCM). The NCM, which is a
      stochastic, birth-death immigration process, does not explicitly represent the
      deterministic factors and therefore cannot be a complete or literal description
      of community assembly. However, its success suggests that chance and immigration
      are important forces in shaping the patterns seen in prokaryotic communities.

PMID- 16584485
TI  - Improved template representation in cpn60 polymerase chain reaction (PCR) product
      libraries generated from complex templates by application of a specific mixture
      of PCR primers.
AB  - Some classes of high G+C content organisms such as the Actinobacteria, which are
      known through culture-based studies to be present in large numbers in particular
      microbial communities, are under-represented or even absent from 16S rRNA or
      cpn60 polymerase chain reaction (PCR) product libraries derived from these
      templates. Using reference cpn60 sequence data from organisms with high G+C
      content genomes, a pair of PCR primers were designed which, when used in
      combination with the previously developed degenerate, universal cpn60 primers,
      improve the representation of templates with high G+C content. The primers were
      validated using a combination of traditional and quantitative real-time PCR on
      both manufactured template mixtures and biological samples. The development and
      optimization of this specific primer mixture represents an improvement of
      established methods and a significant advance in the ability to generate cpn60
      PCR product libraries that more closely represent the sequence diversity in
      complex templates.

PMID- 16584486
TI  - In situ probing of Xylella fastidiosa in honeydew of a xylem sap-feeding insect
      using 16S rRNA-targeted fluorescent oligonucleotides.
AB  - Xylella fastidiosa is a plant pathogen that threatens a US$ 4.6 billion worldwide
      wine and citrus industry. Monitoring its presence and distribution in plants and
      vectors is crucial for designing control strategies, as well as for understanding
      its ecological role and fate. We developed two fluorescent oligonucleotide probes
      complementary to different regions of the 16S rRNA gene of X. fastidiosa. The
      specificity of the newly designed probes S-S-X.fas-0067-a-A-18 and S-S-X.fas-1439
      a-A-18 was demonstrated using fluorescence in situ hybridization (FISH) for 12
      Xylella isolates, 15 closely related microorganisms and three plant endophytes.
      These probes were used to detect and quantify X. fastidiosa in plant sap (average
      value of 2.9 +/- 0.3 x 10(6) cells ml(-1)) from three different citrus orchards.
      In a second experiment, cells were quantified in honeydew (2.2 +/- 0.2 x 10(4)
      cells ml(-1)) collected from the insect vector Bucephalogonia xanthophis during
      the acquisition access period on an infected plant. The number of pathogen cells
      retained or digested by the insect is 10,000 times greater than the estimated
      minimum value to ensure an efficient transmission. Polymerase chain reaction
      (PCR) amplification using specific primers with plant sap and honeydew samples,
      followed by sequencing, confirmed the presence of the plant pathogen. This is the
      first demonstration of FISH being used for environmental samples, such as plant
      sap and insect honeydew, to estimate the abundance of a plant pathogen during
      infection.

PMID- 16584487
TI  - 'Everything is everywhere, but, the environment selects'; what did Baas Becking
      and Beijerinck really say?

PMID- 16584489
TI  - On the causes of persistent apical periodontitis: a review.
AB  - Apical periodontitis is a chronic inflammatory disorder of periradicular tissues
      caused by aetiological agents of endodontic origin. Persistent apical
      periodontitis occurs when root canal treatment of apical periodontitis has not
      adequately eliminated intraradicular infection. Problems that lead to persistent
      apical periodontitis include: inadequate aseptic control, poor access cavity
      design, missed canals, inadequate instrumentation, debridement and leaking
      temporary or permanent restorations. Even when the most stringent procedures are
      followed, apical periodontitis may still persist as asymptomatic radiolucencies,
      because of the complexity of the root canal system formed by the main and
      accessory canals, their ramifications and anastomoses where residual infection
      can persist. Further, there are extraradicular factors -- located within the
      inflamed periapical tissue -- that can interfere with post-treatment healing of
      apical periodontitis. The causes of apical periodontitis persisting after root
      canal treatment have not been well characterized. During the 1990s, a series of
      investigations have shown that there are six biological factors that lead to
      asymptomatic radiolucencies persisting after root canal treatment. These are: (i)
      intraradicular infection persisting in the complex apical root canal system; (ii)
      extraradicular infection, generally in the form of periapical actinomycosis;
      (iii) extruded root canal filling or other exogenous materials that cause a
      foreign body reaction; (iv) accumulation of endogenous cholesterol crystals that
      irritate periapical tissues; (v) true cystic lesions, and (vi) scar tissue
      healing of the lesion. This article provides a comprehensive overview of the
      causative factors of non-resolving periapical lesions that are seen as
      asymptomatic radiolucencies post-treatment.

PMID- 16584490
TI  - The influence of root canal shape on the sealing ability of two root canal
      sealers.
AB  - AIM: To evaluate the influence of root canal form on the sealing ability of two
      root canal sealers. METHODOLOGY: Twenty radiographically confirmed straight and
      20 curved root canals were prepared with a stepback hand filing technique. Root
      canal aberrations created during preparation were determined by the use of double
      exposure radiographic technique. The prepared canals were filled with lateral
      condensation of gutta-percha and one or other of two root canal sealers (Pulp
      Canal Sealer and Sealapex). Leakage along the apical 10 mm of roots was measured
      with a fluid transport model at 1, 3, 6, 9 and 12-month intervals. RESULTS: There
      were no statistically significant differences between straight and curved root
      canals (P > 0.05) for prevalence of root canal transportation. The prevalence of
      apical transportation was 80% in the straight and 85% in the curved root canals.
      A complete seal was more frequently observed in straight canals compared with
      curved canals. Utilizing the pi* index, analysis showed the filling with Sealapex
      allowed more leakage than Pulp Canal Sealer at 1 year. CONCLUSION: Under the
      conditions of the study, root canal form influenced short-term sealing ability.
      In the long-term the seal was affected by the sealer rather than root canal form.

PMID- 16584491
TI  - Ex vivo comparison of digital images with conventional radiographs for detection
      of simulated voids in root canal filling material.
AB  - AIM: To compare the diagnostic potential of direct digital images with
      conventional radiographs for the detection of simulated root canal voids.
      METHODOLOGY: The root canals of 80 extracted maxillary incisors with straight
      root canals were prepared and filled and the specimens divided into two groups:
      (i) a group of 40 teeth without voids; and, (ii) a group of 40 teeth with voids
      created in the root filling. Each root was imaged using the paralleling technique
      with a CCD-based digital system and F-speed film. Totally, there were 240 images:
      conventional radiographs (n = 80), digital images (n = 80) and digital zoomed
      images at 2x magnification (n = 80). These were interpreted for voids by a
      radiologist (without prior knowledge of the distribution of the voids). The
      reliability of the radiologist was confirmed using Cohen's Kappa Statistic, with
      the kappa value found to be >0.08. The sensitivity, specificity and predictive
      values were calculated. The differences in sensitivity and specificity between
      the imaging systems were then assessed using the Exact McNemar significance
      probability at the 95% significance level. RESULTS: The sensitivities (95% CI) of
      conventional radiographs, digital images and zoomed images were 0.68 (0.57-0.78),
      0.83 (0.74-0.91) and 0.80 (0.71-0.89), respectively. The specificities of the
      conventional radiographs, digital and zoomed images were 0.80 (0.71-0.89), 0.83
      (0.74-0.91) and 0.83 (0.74-0.91), respectively. The positive predictive values
      (95% CI) were 0.77 (0.68-0.86), 0.83 (0.74-0.91) and 0.82 (0.74-0.90),
      respectively. The negative predictive values (95% CI) were 0.71 (0.61-0.81), 0.83
      (0.74-0.91) and 0.80 (0.72-0.89), respectively. There were no significant
      differences between the sensitivity and specificity of digital images and
      conventional radiographs, and of digital images and zoomed images during the
      detection of voids in root fillings (P > 0.05). CONCLUSIONS: Under the conditions
      of this laboratory study, the diagnostic performance of digital images and
      conventional radiographs, and between the digital images and digital zoomed
      images for simulated void detection in root fillings were not significantly
      different.

PMID- 16584492
TI  - MTA versus Portland cement as repair material for furcal perforations: a
      laboratory study using a polymicrobial leakage model.
AB  - AIM: To compare the ability of Portland cement and mineral trioxide aggregate
      (MTA) to prevent coronal leakage through repaired furcal perforations in molar
      teeth. METHODOLOGY: The pulp chambers of 36 human mandibular molar teeth were
      accessed and the root canal orifices were located. The roots were horizontally
      sectioned in the middle third. Composite resin was used to fill the root canal
      orifices and the apical end of the roots. Perforations were created in the centre
      of the pulp chamber floor using a size 3 round bur. Thirty teeth were divided
      into two groups (n = 15) and a further six teeth served as controls. In G1, all
      15 perforation defects were repaired with MTA while in G2, Portland cement was
      used. Each tooth was inserted in a silicone tube (bacterial reservoir) with the
      region containing the perforation protruding through the end. The system was
      sterilized and placed in a glass flask containing sterile brain heart infusion
      medium (BHI). The reservoirs were filled with human saliva mixed in BHI and
      system was incubated at 37 degrees C and checked daily for the appearance of
      turbidity in the BHI broth during the following 50 days. The leakage data were
      analysed statistically by a log-rank test (P < 0.05). RESULTS: Eight (53%) of the
      15 samples of the MTA group (G1) and nine (60%) of the 15 samples of the Portland
      cement group (G2) were fully contaminated at 50 days. There was no statistically
      significant difference between the two groups (P > 0.05). CONCLUSION: Portland
      cement and MTA demonstrated a similar ability to seal furcal perforations.

PMID- 16584493
TI  - The relation between apical periodontitis and root-filled teeth in patients with
      periodontal treatment need.
AB  - AIM: To investigate a number of clinical and treatment variables that might have
      influenced the prevalence of apical periodontitis in root-filled teeth in a
      population of periodontally compromised patients. METHODOLOGY: This investigation
      was a retrospective cross-sectional study on data collected from periodontal
      charts in addition to intra-oral full-mouth radiographs from patients attending
      the Department of Periodontology of the Dental School of the Ghent University
      Hospital. Periodontal parameters (clinical attachment loss and the lowest
      marginal bone level, the history of periodontal treatment), endodontic treatment
      (length, homogeneity and overall quality of the root filling) and the quality of
      coronal restorations were related to the prevalence of apical periodontitis. A
      total of 272 root-filled teeth in 94 patients were evaluated. RESULTS: The
      periapical condition was significantly influenced by the quality of the root
      filling and the coronal filling (P < 0.05). More apical periodontitis was seen
      when the coronal level of the root filling exceeded the marginal bone level (P <
      0.005). The marginal periodontal condition seemed to influence the periapical
      status. Teeth with apical periodontitis were associated with significantly more
      extended marginal bone loss (P < 0.001). Significantly less apical periodontitis
      was seen in patients that had received marginal periodontal treatment (P <
      0.005), compared with untreated periodontal patients. CONCLUSIONS: Signs of
      periodontal disease, as reflected by marginal bone loss, are of importance for
      the periapical condition of root-filled teeth. Efforts should be taken in
      preventing spread of infection through the periodontal-endodontic pathway by
      periodontal infection control and a high quality of root filling and coronal
      filling. Care should also be taken to seal the coronal cavity up to the level of
      the root filling, where it is advisable to reduce the coronal level of the root
      filling below or at least at the level of the surrounding marginal bone.

PMID- 16584494
TI  - The influence of haemostatic agents on healing of healthy human dental pulp
      tissue capped with calcium hydroxide.
AB  - AIM: To investigate the hypothesis that different haemostatic agents could impair
      the histological response of human pulps capped with calcium hydroxide.
      METHODOLOGY: Forty-five third molars scheduled for extraction were selected.
      Class I cavities with pulp exposures were prepared. Three agents were used to
      control bleeding: 0.9% saline solution (control, n = 14), 5.25% sodium
      hypochlorite (n = 16) and 2% chlorhexidine digluconate (n = 15). The pulps were
      dressed with hard-setting calcium hydroxide cement. After 7, 30 or 90 days, teeth
      were extracted, formalin-fixed and prepared for histochemical techniques. The
      biological response was categorized using the following criteria: inflammatory
      response, soft tissue organization, reactionary dentine and reparative dentine.
      Data were submitted to statistical analysis, using nonparametric Kruskal-Wallis
      one-way analysis of variance on ranks. Differences amongst groups were detected
      using Dunn's method. RESULTS: The statistical analysis disclosed that whilst
      inflammatory response decreased over time, reactionary dentine deposition and
      reparative dentine formation increased in the latter periods of evaluation (P <
      0.05). The three agents had similar performances for all criteria evaluated. The
      conventional pulp response to calcium hydroxide was observed over time, and
      complete pulp healing was observed in 88% of the specimens after 90 days.
      CONCLUSION: The three haemostatic agents did not impair the healing process
      following pulp exposure and capping with calcium hydroxide at different time
      intervals investigated.

PMID- 16584495
TI  - Biological effects of flowable resin composite on erythrocytes and lymphocytes
      using an in vitro model.
AB  - AIM: The purpose of the study was to evaluate the biological effects of a
      flowable resin composite on erythrocytes and rat spleen lymphocytes (RSL) using
      an in vitro model. METHODOLOGY: Rat spleen lymphocytes were placed into
      microcentrifuge tubes as a pulp model. An artificial pulp exposure was made
      through the top of the microcentrifuge tube with a 16G needle. The exposure site
      was filled with a flowable resin composite and photo-polymerized, and the other
      specimens were not polymerized. The survival rates were determined by a
      haemocytometer. Red blood cell (RBC) suspension (0.5%) was reacted with the
      flowable resin composite. The haemolytic activity was evaluated at room
      temperature (20 degrees C) using a supernatant of each sample by measuring 545 nm
      of absorbency with a spectrophotometer. To evaluate the effect of flowable resin
      composite on RBCs, supernatant and precipitated samples were analysed by sodium
      dodecyl sulphate-polyacrylamide gel (SDS-PAGE). RESULTS: The cell survival rate
      of the polymerized group was significantly lower compared with that of the
      nonpolymerized group at the same areas (P < 0.05). The values of haemolysis
      (absorbency) were 2.16 for the polymerized group, 2.14 for the nonpolymerized
      group, and 2.18 for the control group (saline). There were no significant
      differences among them (P > 0.05). The protein component in the supernatant and
      precipitate exhibited the same reaction with flowable resin composite regardless
      of the completion of the polymerization, resulting in no change of protein band
      mobility on SDS-PAGE. CONCLUSIONS: The degree of haemolysis was not influenced by
      the completion of polymerization. The flowable resin composite tested provoked an
      adverse effect on lymphocytes when it was not polymerized and the degree of
      haemolysis was not affected by the status of the polymerization.

PMID- 16584496
TI  - Orthodontic movement of two root fractured teeth: a case report.
AB  - AIM: To illustrate significant tipping orthodontic movement of root fractured
      teeth. SUMMARY: As the frequency of root fractured maxillary teeth is related to
      increased overjet and reduced lip coverage, orthodontic treatment may increase
      lip coverage and reduce the risk of trauma or its severity. It may also be
      necessary to move previously traumatized teeth. Two root fractured teeth were
      tipped through a considerable angle (19 degrees ) to reduce a large overjet and
      followed up for 5 years. KEY LEARNING POINTS: -- Reduction of large overjets
      involving root fractured teeth may not affect pulp vitality. -- Root fragment
      separation prior to orthodontics did not appear to increase in this patient, but
      angulation of the fragments did not completely follow the major change to the
      coronal part of the tooth.

PMID- 16584497
TI  - Re: A temporary filling material may cause cusp deflection, infractions and
      fractures in endodontically treated teeth.

PMID- 16584500
TI  - Root canal preparation with Endo-Eze AET: changes in root canal shape assessed by
      micro-computed tomography.

PMID- 16584501
TI  - Re: The use of an intra-oral injection of ketorolac in the treatment of
      irreversible pulpitis.

PMID- 16584505
TI  - The endocrine function of adipose tissue: an update.
AB  - Adipose tissue secretes bioactive peptides, termed 'adipokines', which act
      locally and distally through autocrine, paracrine and endocrine effects. In
      obesity, increased production of most adipokines impacts on multiple functions
      such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis,
      blood pressure, lipid metabolism and haemostasis, all of which are linked with
      cardiovascular disease. Enhanced activity of the tumour necrosis factor and
      interleukin 6 are involved in the development of obesity-related insulin
      resistance. Angiotensinogen has been implicated in hypertension and plasminogen
      activating inhibitor-1 (PAI-1) in impaired fibrinolysis. Other adipokines like
      adiponectin and leptin, at least in physiological concentrations, are insulin
      sparing as they stimulate beta oxidation of fatty acids in skeletal muscle. The
      role of resistin is less understood. It is implicated in insulin resistance in
      rats, but probably not in humans. Reducing adipose tissue mass, through weight
      loss in association with exercise, can lower TNF-alpha and IL-6 levels and
      increase adiponectin concentrations, whereas drugs such as thiazolinediones
      increase endogenous adiponectin production. In-depth understanding of the
      pathophysiology and molecular actions of adipokines may, in the coming years,
      lead to effective therapeutic strategies designed to protect against
      atherosclerosis in obese patients.

PMID- 16584506
TI  - The influences of hyperprolactinemia and obesity on cardiovascular risk markers:
      effects of cabergoline therapy.
AB  - OBJECTIVE: In view of the association of hyperprolactinaemia with insulin
      resistance, we hypothesized that patients with hyperprolactinaemia may present
      increased cardiovascular risk markers. DESIGN: Descriptive clinical trial.
      METHODS: Serum glucose, insulin, insulin resistance, lipids, high sensitivity C
      reactive protein (hsCRP), interleukin (IL)-6, tumour necrosis factor (TNF)-alpha
      and soluble E-selectin (sELAM-1) serum levels were determined in 15 patients with
      hyperprolactinaemia at baseline (compared with 20 healthy subjects) and after 12
      weeks of cabergoline therapy (0.5-1 mg twice per week). We also measured
      mononuclear cell NF-kappaB activation and TNF-alpha production in a subset of
      subjects. RESULTS: Serum levels of prolactin (PRL), insulin, insulin resistance
      (HOMA-IR) index and hsCRP were significantly higher in patients than in control
      subjects. Markers of mononuclear cell activation did not differ between the
      groups. Hyperprolactinaemia, BMI and age were predictors of hsCRP. BMI was the
      only predictor of HOMA-IR. Cabergoline therapy significantly reduced serum PRL,
      insulin, hsCRP and sELAM-1 levels. CONCLUSIONS: These data suggest that
      hyperprolactinaemia is associated with insulin resistance related to increased
      BMI and low-grade inflammation independently of BMI. Short-term cabergoline
      therapy can reduce the inflammatory markers.

PMID- 16584507
TI  - 18Flurodeoxyglucose positron emission tomography in the localization of ectopic
      ACTH-secreting neuroendocrine tumours.
AB  - OBJECTIVE: Neuroendocrine tumours (NET) are a rare cause of Cushing's syndrome.
      These tumours can be very small and therefore difficult to identify. Current
      localization techniques include CT, MRI and radioisotope scanning, but in a
      proportion of cases the NET remains occult. Positron emission tomography (PET)
      scanning, is a relatively new imaging modality that is increasingly used to
      detect and monitor lesions with high metabolic activity. We report on the use of
      PET scanning in the evaluation of the ectopic ACTH syndrome. PATIENTS: Three
      patients with ectopic ACTH-dependent Cushing's syndrome with varying difficulty
      in NET localization are included in the report. MEASUREMENT: Positron emission
      tomography scanning using 18flurodeoxyglucose (FDG) identifies tissue with high
      metabolic activity. 18FDG-PET scanning was used in each of these patients and the
      imaging is presented along with biochemical data. RESULTS: In each case the NET
      was easily identified using 18FDG-PET, aiding clinical decision making and
      therapeutic outcome. A cure was identified by clinical resolution of symptoms and
      undetectable ACTH levels postsurgery. CONCLUSIONS: 18FDG-PET assisted in
      localizing small metabolically active NETs, suggesting this imaging modality may
      have a useful role in identifying NET causing Cushing's syndrome as a result of
      ectopic ACTH production.

PMID- 16584508
TI  - Thyroid function in human immunodeficiency virus patients treated with highly
      active antiretroviral therapy (HAART): a longitudinal study.
AB  - OBJECTIVE: Given that few and controversial data have been reported on thyroid
      function in human immunodeficiency virus (HIV) patients on highly active
      antiretroviral therapy (HAART), we further investigated whether HAART affects
      thyroid hormones. DESIGN AND PATIENTS: Two hundred two consecutive adult HIV
      patients in stable clinical condition were enrolled, 182 on HAART and 20 naive;
      128 were rechecked during follow-up. Body mass index (BMI), CD4 cell count, HIV
      RNA, hepatitis C and B virus status and infection duration were determined in all
      HIV patients and HAART duration in treated patients. In all patients and in 60
      controls, the following were measured: FT4 and FT3 by radioimmunoassay; TSH,
      antithyroid peroxidase (TPO) and antithyroglobulin (TG) antibodies by
      immunoradiometric assay. RESULTS: Abnormalities in thyroid function tests were
      found in 23/182 (12.6%) HAART patients, but not in naive patients. Most
      abnormalities were subclinical hypothyroidism, with mean FT4 and TSH levels lower
      and higher, respectively, in HAART patients compared to naive patients and
      controls, FT4 levels being significantly lower than controls. TSH negatively
      correlated with CD4 count nadir and positively with HAART duration. During follow
      up, FT4 and FT3 significantly decreased and TSH increased in patients continuing
      HAART, whereas CD4 counts were unmodified; subclinical hypothyroid conditions
      persisted and further cases occurred, whereas the only hypothyroid patient who
      interrupted HAART shows a normalization of thyroid tests. Patients on stavudine,
      included in most hypothyroid patient protocols, had significantly lower FT4
      levels with prolonged treatment. CONCLUSIONS: HAART, particularly stavudine, is
      associated with a high prevalence of subclinical hypothyroidism. Hypotheses are
      made regarding responsible mechanisms and risk factors. Thyroid function should
      be tested and sequentially rechecked in HAART patients.

PMID- 16584509
TI  - Quality of glucocorticoid replacement in adrenal insufficiency: clinical
      assessment vs. timed serum cortisol measurements.
AB  - OBJECTIVE: Evaluation of glucocorticoid replacement quality in adrenal
      insufficiency (AI) relies primarily on clinical judgement and thus largely
      depends on the physician's expertise. It is a matter of debate whether cortisol
      day curves are of value in assessing glucocorticoid replacement quality. Here we
      compared the results of a structured clinical assessment to the outcome of
      repeated, timed serum cortisol measurements. DESIGN: Cross-sectional study in the
      outpatient department of a university teaching hospital. PATIENTS: Forty-six
      patients (19 men, 27 women, age range 16-76 years) with primary (n = 23) and
      secondary (n = 23) AI on stable replacement with a median dose of 37.5 mg
      cortisone acetate (range 25-50 mg) since 10 +/- 7 years (range 1-31 years).
      MEASUREMENTS: Clinical performance was scored by structured assessment of signs
      and symptoms, physical examination and routine biochemical tests. Serum cortisol
      was measured on two to three separate occasions in three timed samples after the
      morning glucocorticoid dose. Bone mineral density was measured in 15 patients
      with long-standing glucocorticoid replacement. RESULTS: Thirty-seven patients
      were considered well replaced, whereas clinical scores suggested over- or under
      replacement in five and four, respectively. There was no correlation of the
      clinical score with total or body weight-adjusted glucocorticoid dose. The mean z
      score of serum cortisol differed significantly between under- and over-replaced
      patients (P < 0.05) but neither group differed significantly from well-replaced
      patients. Bone mineral density was normal in all patients studied. CONCLUSIONS:
      Our results suggest that serum cortisol day curves are of limited value in the
      monitoring of glucocorticoid replacement. Bone mineral density in AI is generally
      normal and does not require routine follow-up.

PMID- 16584510
TI  - Pulsed tissue Doppler identifies subclinical myocardial biventricular dysfunction
      in active acromegaly.
AB  - OBJECTIVE: The aim of this study was to assess the role of pulsed tissue Doppler
      (TD) to identify left (LV) and right ventricular (RV) myocardial regional
      involvement in acromegaly. PATIENTS AND MEASUREMENTS: Thirty active acromegaly
      patients, free of diabetes mellitus, thyroid dysfunction, valvular and coronary
      heart disease, clinically overt heart failure, and 30 sex- and age-matched
      healthy controls underwent standard Doppler echocardiography and pulsed TD, by
      placing the sample volume at the level of basal posterior septum, LV lateral
      mitral annulus and RV lateral tricuspid annulus. Myocardial systolic (S(m)) and
      diastolic velocities (E(m)/A(m) ratio) and time-intervals of relaxation (RT(m)),
      precontraction (PCT(m)) and contraction (CT(m)) and the PCT(m)/CT(m) ratio were
      measured at each level. RESULTS: The two groups had similar heart rate, whereas
      acromegaly patients had higher body mass index, systolic and diastolic blood
      pressure, LV mass and impaired Doppler indexes of LV and RV diastolic function,
      without any difference in the global systolic function. At TD, acromegaly
      patients showed significantly delayed RT(m) and PCT(m,) reduced E(m)/A(m), S(m)
      and increased PCT(m)/CT(m) of posterior septum, mitral annulus and tricuspid
      annulus in comparison with controls. By separate multilinear regression analyses,
      after adjusting for body mass index, heart rate, diastolic blood pressure and LV
      mass index, age was the main independent determinant of tissue Doppler diastolic
      but not of systolic indexes. CONCLUSIONS: In active acromegaly, pulsed TD
      confirms LV and RV diastolic abnormalities detectable by standard Doppler,
      additionally identifying subclinical biventricular impairment of systolic
      function.

PMID- 16584511
TI  - HEX, PAX-8 and TTF-1 gene expression in human thyroid tissues: a comparative
      analysis with other genes involved in iodide metabolism.
AB  - OBJECTIVE: Benign and malignant thyroid tumours are characterized by alterations
      of the expression level of thyroid-specific genes involved in the iodide
      metabolism. Imbalance in the levels of transcription factors has been recognized
      as a critical molecular event in the development of neoplasm. The delineation of
      eventual correlations existing between the expression of transcription factors
      and of putative target genes in physiological and pathological conditions could
      be relevant to better understand tumorigenesis. PATIENTS AND METHODS: We examined
      the expression levels of transcription factors involved in thyroid development
      [thyroid transcription factor 1 (TTF-1), paired box gene 8 (PAX-8) and
      haematopoietically expressed homeobox (HEX)] in 101 thyroid tissues, including 14
      normal thyroid tissues, 13 hyperfunctioning tissues, 27 benign adenomas and 47
      follicular or papillary carcinomas. Then, we compared their expression levels
      with those of thyroid-specific genes involved in iodide metabolism. RESULTS: In
      benign tumours, PAX-8 and TTF-1 gene expression levels were not significantly
      different from the expression levels in normal tissues. However, a significant
      decrease was found in carcinomas. Interestingly, HEX gene expression was
      significantly decreased in both hyper- and hypofunctioning benign tissues and
      also in carcinomas. Expression levels of Pendred syndrome (PDS), natrium iodine
      symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO) and dual oxidase 1
      or 2 (DUOX2) genes were significantly correlated with the expression of PAX-8 and
      with that of HEX. Expression level of TTF-1 was weakly correlated only with the
      expression levels of PDS and DUOX2. CONCLUSION: Our findings suggest that
      alterations in the transcription factors PAX-8, TTF-1 and HEX gene expression, by
      acting individually or together, have a role in both thyroidal tumorigenesis and
      in the dedifferentiation process.

PMID- 16584512
TI  - Pattern of bone mineral density in patients with sporadic idiopathic
      hypoparathyroidism.
AB  - OBJECTIVE: Measurement of bone mineral density (BMD) in patients with
      hypoparathyroidism directly addresses the effect of chronic under-exposure of
      bone to PTH. Because post-thyroidectomy hypoparathyroidism is potentially
      complicated by the pre-existence of thyrotoxicosis and the need for postoperative
      thyroxine replacement, we have studied a large group of patients with sporadic
      hypoparathyroidism who have been followed up in our endocrine clinic. Studies
      conducted in limited number of patients with sporadic idiopathic
      hypoparathyroidism (SIH) have suggested an increase in BMD in such patients. In
      this current study, we have measured BMD in a large cohort of patients with SIH
      and have assessed the relationship of BMD with duration of disease and with the
      adequacy of treatment, as indicated by follow-up serum calcium, phosphate and
      alkaline phosphatase levels. DESIGN: Case control study and intra-group
      comparison. SUBJECTS: Forty-seven patients (M : F ratio 23 : 24) with SIH who had
      been reviewed during 2003-2004 in our endocrine clinic were recruited for this
      study. Their mean age (+/- SD) was 34.6 +/- 13.6 years and the duration from the
      time of initial diagnosis was 9.6 +/- 8.5 years. Forty-eight match healthy
      volunteers were recruited from hospital staff and from normocalcaemic relatives.
      METHODS: Bone mineral density was measured at total lumbar spine (L1-L4), hip and
      forearm by dual energy X-ray absorptiometry (DXA). The relationship of BMD was
      analysed with duration of disease symptoms (group I, < or = 1 year, group II, > 1
      and < 5 years and group III, > or = 5 years) and mean serum total calcium
      observed during follow-up (group A, calcium < or = 1.79 mmol/l and group B, > or
      = 1.80 mmol/l). RESULTS: Patients with SIH showed significantly higher BMD at
      total lumbar spine and hip when compared to controls (1.098 +/- 0.187 vs. 0.936
      +/- 0.131 g/cm2 and 0.967 +/- 0.141 vs. 0.882 +/- 0.149 g/cm2, P < 0.001 for
      both). BMD in the forearm was not significantly different in patients and
      controls. The age- and BMI-adjusted lumbar spine BMD showed correlation with
      duration of disease (r = 0.348 and P = 0.019). Patients with longer duration of
      hypoparathyroidism had higher BMD at lumbar spine (group I vs. group III, 0.951
      +/- 0.132 vs. 1.156 +/- 0.180 g/cm2, P < 0.05). There was no significant
      correlation between BMD values in patients with SIH and their mean serum total
      calcium levels during the period of follow-up (r = 0.192, P = 0.206). Neither was
      the mean BMD significantly different between group A and B. Serum total alkaline
      phosphatase showed a significant negative correlation with BMD at lumbar spine (r
      = -0.445, P = 0.012). CONCLUSIONS: Patients with sporadic idiopathic
      hypoparathyroidism have increased mean BMD in the lumbar spine and hip but not in
      the forearm, compared to normal matched healthy controls. The increase in BMD is
      related to the duration of the disease rather than the serum calcium levels.

PMID- 16584513
TI  - Physiological and catecholamine response to sympathetic stimulation in turner
      syndrome.
AB  - OBJECTIVE: Women with Turner syndrome have increased heart rate and high blood
      pressure (BP), and have been described as having high tolerance for emotional
      stress. We hypothesized that women with Turner syndrome have reduced
      catecholaminergic and physiological response to sympathetic stimulation, and that
      changes in BP and heart rate are related to their catecholamine response to
      sympathetic stimulation. DESIGN AND PATIENTS: Ten young women with Turner
      syndrome, age 17-34 years were the subjects of this study. Their response to
      sympathetic stimulation was compared to a group of 10 age-matched healthy women.
      MEASUREMENTS: After a period of 30 min resting, subjects and controls were
      subjected to an escalating series of sympathetic stimulation: orthostatic, cold
      pressor and exercise, and their plasma catecholamines and haemodynamic response
      were monitored and compared to resting levels. RESULTS: Resting heart rate was
      higher in Turner syndrome patients at 83 +/- 9 beats per min (bpm, mean +/- SD),
      as compared to controls (74 +/- 10 bpm, P < 0.05). Their supine BP was also
      higher at 122 +/- 9/84 +/- 6 vs. 106 +/- 11/70 +/- 9 mmHg (P < 0.02/< 0.02). The
      corresponding resting norepinephrine, but not epinephrine, was higher in Turner
      syndrome patients (2.54 +/- 1.09 nmol/l) as compared to controls (1.69 +/- 0.55
      nmol/l, P < 0.02). In response to orthostatic stimulation and cold pressor test
      the systolic, but not the diastolic BP or heart rate, increased in Turner
      syndrome patients but not in the control group (P < 0.01). The change in blood
      catecholamine levels was comparable in both groups. Their physiological response
      to exercise was normal. Yet, the exercise-induced surge of norepinephrine and
      epinephrine in Turner syndrome patients was lower (P < 0.02). CONCLUSIONS: Turner
      syndrome is associated with dysregulation of the sympathetic nervous system
      (SNS), leading to tachycardia and high BP, increased resting norepinephrine
      levels, and a greater tolerance of the cathecholamine response to exercise.

PMID- 16584514
TI  - Phenotypic variability in children with growth hormone deficiency associated with
      posterior pituitary ectopia.
AB  - OBJECTIVE: The cause of posterior pituitary ectopia (PPE) with anterior pituitary
      hormone deficiencies is unknown. This disease is usually considered sporadic. The
      objective of this study was to improve the phenotypic characterization of
      children with PPE and growth hormone deficiency (GHD) to seek insight into the
      mechanisms underlying abnormal pituitary-gland development. PATIENTS AND DESIGN:
      Sixty children with GHD and PPE were evaluated in this retrospective chart review
      (1988-2003). RESULTS: Known extra-pituitary birth defects (BD) were present in 31
      patients (BD+, 52%) and absent in 29 patients (BD-). Among BD+ patients, seven
      had well-defined syndromes (Fanconi anaemia, n = 2; Pallister-Hall, n = 1;
      Currarino, n = 2; or Stilling-Duane, n = 2) and the other 24 had 53 BDs, mainly
      involving the brain, eyes and the craniofacial structures (n = 27, 51%) but also
      affecting the heart, skeleton, kidneys, gastrointestinal tract and skin. Of the
      60 patients, seven (12%) were born to consanguineous parents (five sporadic and
      two familial cases). There were seven (12%) familial cases, with wide variations
      in clinical presentation, endocrine profiles and magnetic resonance imaging (MRI)
      findings within families and various patterns consistent with autosomal dominant,
      recessive or X-linked transmission. CONCLUSION: The high rate of extra-pituitary
      BDs and of familial components supports a role for genetic factors in the
      pathogenesis of this heterogeneous disorder. A detailed record of phenotypic
      abnormalities in patients with GHD and PPE might produce useful hypotheses for
      genetic studies.

PMID- 16584515
TI  - Effects of growth reduction therapy using high-dose 17beta-estradiol in 26
      constitutionally tall girls.
AB  - OBJECTIVE: The efficacy and safety of height-limiting therapy with high-dose
      17beta-oestradiol in girls with constitutionally tall stature (CTS) are
      controversial. We evaluated the effectiveness of high-dose 17beta-oestradiol in
      premenarchal girls with CTS treated until their bone age reached 14 years.
      DESIGN: We retrospectively reviewed the medical records of the girls managed
      between 1989 and 2000 with high-dose 17beta-estradiol for CTS with a predicted
      final height greater than +3SDs. PATIENTS: Twenty-six girls met our inclusion
      criteria. At baseline, mean chronological age was 12.06 +/- 1.51 years and mean
      height was 171.1 +/- 6.5 cm with a height standard deviation score of 4.5 +/-
      0.24, and mean predicted final height was 183.0 +/- 4.2 cm. Treatment was stopped
      when bone age reached 14 years; mean treatment duration was 1.62 +/- 0.76 years.
      MEASUREMENTS: The following were obtained at 6-month intervals: height, body
      weight, Tanner stage, bone age, plasma cholesterol and triglycerides, plasma
      glucose and side effects. A mailed questionnaire on final height and satisfaction
      was sent 2 years after treatment discontinuation (response rate, 24/26). Results
      Final height was significantly (P < 0.001) reduced, by 2.4 +/- 3.2 cm, as
      compared to predictions. High-dose 17beta-estradiol therapy decreased growth
      velocity and significantly increased skeletal maturation (P < 0.001). Linear
      growth after treatment discontinuation was 3.3 +/- 1.9 cm. No serious side
      effects were recorded. Most of the patients were satisfied with the treatment.
      CONCLUSION: High-dose 17beta-estradiol was moderately effective in reducing final
      height and should probably be reserved for selected patients, particularly as
      knowledge on potential long-term side effects is lacking.

PMID- 16584517
TI  - Characterization of the metabolic phenotypes of Cushing's syndrome and growth
      hormone deficiency: a study of body composition and energy metabolism.
AB  - OBJECTIVE: A comparison of the severity and distribution of perturbations in body
      composition and their relationship to energy metabolism in glucocorticoid excess
      and GH deficiency (GHD) has not been undertaken before. The aim of this study was
      to investigate the impact of Cushing's syndrome (CS) and GHD on whole and
      regional body composition and energy metabolism. DESIGN: Cross-sectional study
      design. PATIENTS: Eighteen subjects with CS (12 women, aged = 41.5 +/- 3.0 years,
      24-h urinary free cortisol = 1601 +/- 361 nmol/day, normal < 300 nmol/day), 22
      subjects with GHD (14 women, age = 42.9 +/- 2.9 years) and 18 normal subjects (11
      women, age = 46.8 +/- 2.8 years). MEASUREMENTS: Lean body mass (LBM), fat mass
      (FM) and regional body composition were assessed by dual-energy X-ray
      absorptiometry (DEXA). Resting energy expenditure (REE) and fat oxidation (Fox)
      were assessed by indirect calorimetry. RESULTS: Mean percentage FM was
      significantly greater by 30% in CS (P = 0.002) and 22% in GH-deficient subjects
      (P = 0.014) than in normal subjects. LBM was significantly lower by 15% in CS (P
      = 0.002) and 11% in GHD (P = 0.013). In CS, the proportion of lean tissue in the
      limbs was 12% less than in normal (P = 0.001) and GH-deficient subjects (P =
      0.0005). Truncal fat represented a greater proportion of total FM in CS (52.5 +/-
      1.8%vs. 46.9 +/- 1.3%, P = 0.014) than in normal subjects, but not in GHD. REE
      and Fox, corrected for LBM, were significantly lower in GHD (P < 0.02 for both
      vs. normal) but not in CS. CONCLUSION: FM was higher and LBM lower in both CS and
      GHD. However, there is a greater abnormality of regional body composition in
      patients with CS who exhibit a lower limb lean mass and a greater truncal fat.
      Reduced REE and Fox contribute to increased adiposity in GHD. As REE and Fox are
      not perturbed in CS, other mechanisms must explain the marked gain in truncal and
      total fat.

PMID- 16584516
TI  - A bioluminescence assay for thyrotropin receptor antibodies predicts serum
      thyroid hormone levels in patients with de novo Graves' disease.
AB  - BACKGROUND: TSH receptor antibodies (TBII) in Graves' disease (GD) may be TSH
      receptor stimulating (TSAb) and blocking (TBAb) antibodies. In commercially
      available assays however, only total TBII titres can be measured, without
      discriminating between TSAb and TBAb. OBJECTIVE: To design a TBII bioassay to
      detect of TSAb and to correlate TSAb activity with severity of hyperthyroidism in
      de novo GD patients. PATIENTS: Thirty-five patients with de novo GD and 27
      controls. METHODS: The JP-26-26 cell line, which constitutively expresses the TSH
      receptor (TSHR), was stably transfected with a cyclic adenosine monophosphate
      responsive element--luciferase construct. The clone B1 exhibited a near linear
      increase in luminescence from 0.2 mU/l to 50 mU/l bovine TSH and was used as a
      TBII bioassay. TBII, free T4 and TSH were measured in the sera of all patients
      and controls. RESULTS: In the sera of 35 GD patients, TBII titres did not
      correlate with serum free T4 concentrations. In contrast, a strong and highly
      significant correlation was found between TSHR stimulating activity
      (luminescence) as measured with the TBII bioassay and serum free T4 levels (R =
      0.80, P < 0.001). Interestingly, the luminescence/TBII ratio had a wide range at
      low TBII titres, whereas high TBII titres were associated with a low degree of
      TSHR activation. The TBII bioassay also detected TBAb in GD patients who
      spontaneously developed hypothyroidism. CONCLUSIONS: The B1-TBII-bioassay as
      developed in our laboratory has a high sensitivity for the detection of TSAb in
      GD and predicts the severity of hyperthyroidism in untreated GD patients. In
      addition, we found that high TBII titres are associated with weak TSHR
      activation.

PMID- 16584518
TI  - Effects of growth hormone on insulin resistance and atherosclerotic risk factors
      in obese type 2 diabetic patients with poor glycaemic control.
AB  - OBJECTIVE: We aimed to evaluate the combined effects of GH treatment and diet
      restriction on lipolysis and anabolism, insulin resistance and atherosclerotic
      risk factors in obese patients with type 2 diabetes mellitus (T2DM). SUBJECTS:
      This randomized, double-blind, placebo-controlled study included 24 obese T2DM
      patients (male : female = 12 : 12, mean age 53.7 +/- 7.2 years) with poor
      glycaemic control (fasting plasma glucose 10.673 +/- 1.121 mmol/l, HbA(1C) 9.9 +/
      2.3%). Sixteen of these patients were treated with recombinant human GH (1-1.5
      units/day, 5 days/week) while undergoing diet restriction and exercise for 12
      weeks. METHODS: Anthropometric and bioelectrical impedance measurements were
      undertaken to determine the lean body mass and total body fat. Computed
      tomography (CT) was performed to estimate visceral and subcutaneous fat
      distribution at the umbilicus level and the muscle area of the midthigh. Insulin
      resistance was measured by the insulin tolerance test (ITT) and by the
      homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: The ratios
      VSR (visceral fat area/subcutaneous fat area) and VMR (visceral fat area/thigh
      muscle area) were significantly decreased in the GH-treated group compared to the
      control group. An increase in lean body mass was observed in the GH-treated
      group. Levels of total cholesterol, triglyceride, free fatty acid (FFA),
      fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) were significantly
      decreased after GH treatment. Fasting glucose levels decreased similarly (P <
      0.05 anova) in both groups during the treatment period. Fasting C-peptide levels
      significantly increased, whereas insulin levels significantly decreased, in the
      GH-treated group, but no changes were observed in the control group. The insulin
      sensitivity index (ISI) was significantly increased in the GH-treated group (1.3
      +/- 1.4 vs. 1.9 +/- 1.0%/min, P < 0.05). CONCLUSIONS: GH treatment in obese T2DM
      patients with poor glycaemic control is beneficial in decreasing the amount of
      visceral fats, and may therefore result in improvements in insulin resistance,
      atherosclerotic risk factors and dyslipidaemia.

PMID- 16584519
TI  - Comorbidity in newly diagnosed thyroid cancer patients: a population-based study
      on prevalence and the impact on treatment and survival.
AB  - BACKGROUND: Comorbidity may be an important contributory factor to differences in
      the treatment and outcome of cancer, especially in older patients. It might also
      provide information on the aetiology of the cancer in cases of high or low
      frequency. The aim of this study was to describe the spectrum of comorbidity and
      the possible impact on treatment and survival in newly diagnosed thyroid cancer
      (TC). DESIGN: A population-based observational study. SETTING: The Eindhoven
      Cancer Registry, Comprehensive Cancer Centre South (IKZ), the Netherlands.
      METHODS: Demographic, histological and treatment data on all 417 TC patients
      diagnosed between 1 January 1993 and 31 December 2002 were collected and followed
      up till 2004. An adapted version of the list of Charlson was used for
      registration of clinically relevant concomitant disorders. The prevalence of
      comorbidity at diagnosis was analysed according to gender, age, histological type
      and therapy. Crude 6-month and 1- and 5-year survival rates were determined. A
      regression analysis was performed to identify independent variables related to
      survival. RESULTS: Information on comorbidity was available for 378 patients
      (91%). Comorbidity was present in 32% of the patients; 23% had one and 12% had
      two or more concomitant diseases. The prevalence of comorbidity increased with
      age. Hypertension was the most frequent comorbidity (18%), followed by 'other
      cancers' (7%), cardiovascular diseases (6%) and diabetes mellitus (6%). The
      prevalence of hypertension was twice as high as expected at all age groups. Six
      patients > 60 years had had tuberculosis. Initial surgical treatment was
      negatively related to the presence of concomitant diseases in patients < 70 years
      (P = 0.02), but not in patients > or = 70 years. Comorbidity was not
      independently associated with crude survival up to 5 years. CONCLUSIONS: A
      previous diagnosis of hypertension was associated with TC. The use of external
      radiation for diagnostic and therapeutic procedures for tuberculosis probably
      explains the high prevalence of former tuberculosis in elderly TC patients.
      Treatment choices appeared to be influenced by the presence of comorbidity.
      Comorbidity did not affect survival up to 5 years; a study with a longer period
      of follow-up is needed.

PMID- 16584520
TI  - Influence of parasellar extension of macroprolactinomas defined by magnetic
      resonance imaging on their responsiveness to dopamine agonist therapy.
AB  - OBJECTIVE AND DESIGN: The resistance of macroprolactinomas to dopamine agonist
      (DA) therapy, whether defined as an absence of PRL normalization or the lack of
      significant tumour shrinkage after prolonged treatment at high doses, is usually
      regarded as unpredictable. The aim of this retrospective study, conducted in a
      teaching hospital, was to determine whether cavernous sinus (CS) invasion
      assessed by magnetic resonance imaging (MRI) is associated with a higher rate of
      resistance to DA therapy. METHODS: Forty-nine patients with a macroprolactinoma
      were included in this study and classified into four groups according to the
      percentage of encasement of the intracavernous internal carotid artery (ICA) by
      the tumour. All patients received DA as the primary treatment, mainly cabergoline
      (CAB). PRL normalization and tumour shrinkage during treatment were evaluated as
      a function of CS invasion. RESULTS: Tumours encasing more than three-quarters of
      the intracavernous ICA (group 4) were less responsive to DA therapy, exhibiting a
      lower rate of early (< or = 3 months) PRL normalization (8%vs. 69% in the others
      groups; P < 0.01) under a higher dose of CAB (median: 3.5 mg vs. 1.0 mg per week;
      P < 0.01). CS invasion was a strongly significant and independent predictor of
      hormonal resistance to CAB (P < 0.01). This hormonal resistance occurred in eight
      patients (16%), all but one belonging to group 4. Significant tumour shrinkage
      was observed in 31 out of 45 assessable cases (69%) and was more likely to occur
      in the case of PRL normalization (P < 0.01). CONCLUSIONS: Parasellar extension of
      macroprolactinomas, assessed on the basis of strict MRI criteria, may predict a
      negative response to DA. The responsiveness of noninvasive macroprolactinomas
      (over 90%) is similar to that reported in microprolactinomas, whereas invasive
      tumours are resistant to treatment in more than 50% of cases.

PMID- 16584521
TI  - Effects of oestradiol and oestroprogestin on erythrocyte antioxidative enzyme
      system activity in postmenopausal women.
AB  - OBJECTIVE: Data concerning the relationship between sex steroid hormones and the
      cellular antioxidative enzyme system are controversial. We investigated the
      effects of oestradiol deficiency after menopause and the influence of transdermal
      oestradiol therapy (ET) and hormonal (oestradiol plus medroxyprogesterone)
      replacement therapy (HT) on erythrocyte superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px) and catalase (CAT). GSH and selenium (Se) concentrations were
      also estimated. Serum lipid peroxide (LPO) levels were measured as an indicator
      of free-radical production and lipid peroxidation. PATIENTS: The study group
      consisted of 80 postmenopausal women, divided into two subgroups: 26 women with
      surgically induced menopause (ET1) and 54 women with physiological menopause
      (HT1). Forty premenopausal healthy volunteers were controls (C group). RESULTS:
      LPO was higher in postmenopausal women and decreased after both ET and HT. GSH-Px
      and GSH were lower in the postmenopausal groups but increased significantly after
      both types of therapy. Se concentrations did not differ significantly among the
      groups. CAT activities were similar in all groups and decreased after ET and HT.
      SOD activities in postmenopausal women were similar to those in the C group and
      did not change significantly after treatment. CONCLUSIONS: The administration of
      natural oestrogens to postmenopausal women diminishes oxidative stress and
      increases antioxidative cell potency.

PMID- 16584522
TI  - Uterine vein and maternal urinary levels of activin A and inhibin A in pre
      eclampsia patients.
AB  - OBJECTIVES: The aims of this study were to investigate if (i) urinary
      concentrations of activin A and inhibin A are altered in pre-eclampsia (PE) and
      (ii) to study the relationship between uterine vein and peripheral vein
      concentrations of these hormones in PE patients. DESIGN AND METHOD: In a
      retrospective study, maternal peripheral vein and uterine vein serum and maternal
      urine samples collected at the time of delivery were analysed. There were three
      groups of patients; (i) group 1: term normal pregnancies (n = 19) (ii) group 2:
      patients who developed PE < or = 37 weeks (n = 17) and (iii) group 3: patients
      who developed PE 37-40 weeks (n = 8). Serum and urinary activin A, follistatin,
      inhibin A and pro alpha C and urinary creatinine levels were measured using
      enzyme immunoassays in the laboratory. RESULTS: Normal pregnant urine samples had
      very low levels of activin A and inhibin A. Both groups 2 and 3 PE patients had
      significantly higher levels of inhibin A (P < 0.001) and activin A (P < 0.001)
      compared to the controls. Pro-alpha C was not altered and follistatin was below
      the detection limit of the assay in the urine. Maternal peripheral serum activin
      A and inhibin A were significantly higher in groups 2 (P < 0.001) and 3 (P <
      0.05) patients compared to the controls. Pro-alpha C-containing inhibins were
      higher in group 2 patients (P < 0.05) compared to the controls in the peripheral
      circulation. Uterine vein serum activin A and inhibin A levels were also
      significantly higher in groups 2 (P < 0.001) and 3 (P < 0.05) patients compared
      to the controls. There was a highly significant positive correlation between
      peripheral and uterine vein serum concentrations of activin A, follistatin,
      inhibin A and pro alpha C, suggesting the same source for these proteins in PE.
      CONCLUSION: Urinary activin A and inhibin A are raised in groups 2 and 3 PE
      patients. The magnitude of rise (> 25-fold) suggests these proteins may rise in
      patients before the onset of the clinical symptoms of PE. Uterine vein levels of
      these proteins are also raised in PE.

PMID- 16584523
TI  - Prolonged follow-up of multinodular goitre patients treated with radioiodine
      preceded or not by human recombinant TSH.

PMID- 16584524
TI  - Inadequate growth hormone suppression following an octreotide test dose predicts
      the need for adjuvant therapy to achieve 'safe' growth hormone levels.

PMID- 16584525
TI  - Hypovitaminosis D among unselected medical inpatients and outpatients in Northern
      Italy.

PMID- 16584526
TI  - Subclinical hypothyroidism and mortality in women with type 2 diabetes.

PMID- 16584527
TI  - One year ago not business as usual: wound management, infection and
      psychoemotional control during tertiary medical care following the 2004 Tsunami
      disaster in southeast Asia.
AB  - INTRODUCTION: Following the 2004 tsunami disaster in southeast Asia severely
      injured tourists were repatriated via airlift to Germany. One cohort was triaged
      to the Cologne-Merheim Medical Center (Germany) for further medical care. We
      report on the tertiary medical care provided to this cohort of patients. METHODS:
      This study is an observational report on complex wound management, infection and
      psychoemotional control associated with the 2004 Tsunami disaster. The setting
      was an adult intensive care unit (ICU) of a level I trauma center and subjects
      included severely injured tsunami victims repatriated from the disaster area (19
      to 68 years old; 10 females and 7 males with unknown co-morbidities). RESULTS:
      Multiple large flap lacerations (2 x 3 to 60 x 60 cm) at various body sites were
      characteristic. Lower extremities were mostly affected (88%), followed by upper
      extremities (29%), and head (18%). Two-thirds of patients presented with combined
      injuries to the thorax or fractures. Near-drowning involved the aspiration of
      immersion fluids, marine and soil debris into the respiratory tract and all
      patients displayed signs of pneumonitis and pneumonia upon arrival. Three
      patients presented with severe sinusitis. Microbiology identified a variety of
      common but also uncommon isolates that were often multi-resistant. Wound
      management included aggressive debridement together with vacuum-assisted closure
      in the interim between initial wound surgery and secondary closure. All patients
      received empiric anti-infective therapy using quinolones and clindamycin, later
      adapted to incoming results from microbiology and resistance patterns. This
      approach was effective in all but one patient who died due to severe fungal
      sepsis. All patients displayed severe signs of post-traumatic stress response.
      CONCLUSION: Individuals evacuated to our facility sustained traumatic injuries to
      head, chest, and limbs that were often contaminated with highly resistant
      bacteria. Transferred patients from disaster areas should be isolated until their
      microbial flora is identified as they may introduce new pathogens into an ICU.
      Successful wound management, including aggressive debridement combined with
      vacuum-assisted closure was effective. Initial anti-infective therapy using
      quinolones combined with clindamycin was a good first-line choice.
      Psychoemotional intervention alleviated severe post-traumatic stress response.
      For optimum treatment and care a multidisciplinary approach is mandatory.

PMID- 16584528
TI  - A validated clinical approach for the management of aspergillosis in critically
      ill patients: ready, steady, go!
AB  - The clinical relevance of recovering Aspergillus species in intensive care unit
      patients is unknown. Diagnosis of invasive pulmonary aspergillosis is extremely
      difficult because there are no specific tests sensitive enough to detect it. The
      rapidly fatal prognosis of this infection without treatment justifies early
      antifungal therapy. A clinical algorithm may aid clinicians to manage critically
      ill patients from whose respiratory specimens Aspergillus spp. have been
      isolated. This new tool needs to be validated in a large cohort of patients
      before it can be recommended.

PMID- 16584529
TI  - Rescue therapy in septic shock--is terlipressin the last frontier?
AB  - Use of terlipressin, an analogue of vasopressin, can be considered in septic
      shock patients with intractable hypotension and high cardiac output in whom fluid
      resuscitation and high-dose conventional catecholamines have failed. The effects
      of this agent on organ function are poorly evaluated in humans. The limited
      number of patients evaluated precludes any analysis of adverse outcomes and
      prognosis.

PMID- 16584530
TI  - TGF beta-induced cartilage repair is maintained but fibrosis is blocked in the
      presence of Smad7.
AB  - Cartilage damage in osteoarthritis (OA) is considered an imbalance between
      catabolic and anabolic factors, favoring the catabolic side. We assessed whether
      adenoviral overexpression of transforming growth factor-beta (TGFbeta) enhanced
      cartilage repair and whether TGFbeta-induced fibrosis was blocked by local
      expression of the intracellular TGFbeta inhibitor Smad7. We inflicted cartilage
      damage by injection of interleukin-1 (IL-1) into murine knee joints. After 2
      days, we injected an adenovirus encoding TGFbeta. On day 4, we measured
      proteoglycan (PG) synthesis and content. To examine whether we could block
      TGFbeta-induced fibrosis and stimulate cartilage repair simultaneously, we
      injected Ad-TGFbeta and Ad-Smad7. This was performed both after IL-1-induced
      damage and in a model of primary OA. In addition to PG in cartilage, synovial
      fibrosis was measured by determining the synovial width and the number of
      procollagen I-expressing cells. Adenoviral overexpression of TGFbeta restored the
      IL-1-induced reduction in PG content and increased PG synthesis. TGFbeta-induced
      an elevation in PG content in cartilage of the OA model. TGFbeta-induced synovial
      fibrosis was strongly diminished by simultaneous synovial overexpression of Smad7
      in the synovial lining. Of great interest, overexpression of Smad7 did not reduce
      the repair-stimulating effect of TGFbeta on cartilage. Adenoviral overexpression
      of TGFbeta stimulated repair of IL-1- and OA-damaged cartilage. TGFbeta-induced
      synovial fibrosis was blocked by locally inhibiting TGFbeta signaling in the
      synovial lining by simultaneously transfecting it with an adenovirus
      overexpressing Smad7.

PMID- 16584531
TI  - Genetic control of hippocampal neurogenesis.
AB  - Adult neurogenesis in the hippocampus is under complex genetic control. A recent
      comparative study of two inbred mouse strains using quantitative trait locus
      analysis has revealed that cell survival is most highly correlated with
      neurogenesis and identified candidate genes for further investigation.

PMID- 16584532
TI  - The system is broken.
AB  - When a scientist doing work in genomics, or cell biology, or biochemistry, or
      immunology submits a grant proposal to the US National Institutes of Health
      (NIH), the largest supporter of life science research in the world, his or her
      chance of it being funded are at historic lows.

PMID- 16584534
TI  - Chest wall mechanics during pressure support ventilation.
AB  - INTRODUCTION: During pressure support ventilation (PSV) a part of the breathing
      pattern is controlled by the patient, and synchronization of respiratory muscle
      action and the resulting chest wall kinematics is a valid indicator of the
      patient's adaptation to the ventilator. The aim of the present study was to
      analyze the effects of different PSV settings on ventilatory pattern, total and
      compartmental chest wall kinematics and dynamics, muscle pressures and work of
      breathing in patients with acute lung injury. METHOD: In nine patients four
      different levels of PSV (5, 10, 15 and 25 cmH2O) were randomly applied with the
      same level of positive end-expiratory pressure (10 cmH2O). Flow, airway opening,
      and oesophageal and gastric pressures were measured, and volume variations for
      the entire chest wall, the ribcage and abdominal compartments were recorded by
      opto-electronic plethysmography. The pressure and the work generated by the
      diaphragm, rib cage and abdominal muscles were determined using dynamic pressure
      volume loops in the various phases of each respiratory cycle: pre-triggering,
      post-triggering with the patient's effort combining with the action of the
      ventilator, pressurization and expiration. The complete breathing pattern was
      measured and correlated with chest wall kinematics and dynamics. RESULTS: At the
      various levels of pressure support applied, minute ventilation was constant, with
      large variations in breathing frequency/ tidal volume ratio. At pressure support
      levels below 15 cmH2O the following increased: the pressure developed by the
      inspiratory muscles, the contribution of the rib cage compartment to the total
      tidal volume, the phase shift between rib cage and abdominal compartments, the
      post-inspiratory action of the inspiratory rib cage muscles, and the expiratory
      muscle activity. CONCLUSION: During PSV, the ventilatory pattern is very
      different at different levels of pressure support; in patients with acute lung
      injury pressure support greater than 10 cmH2O permits homogeneous recruitment of
      respiratory muscles, with resulting synchronous thoraco-abdominal expansion.

PMID- 16584536
TI  - The contributions of normal variation and genetic background to mammalian gene
      expression.
AB  - BACKGROUND: Qualitative and quantitative variability in gene expression
      represents the substrate for external conditions to exert selective pressures for
      natural selection. Current technologies allow for some forms of genetic
      variation, such as DNA mutations and polymorphisms, to be determined accurately
      on a comprehensive scale. Other components of variability, such as stochastic
      events in cellular transcriptional and translational processes, are less well
      characterized. Although potentially important, the relative contributions of
      genomic versus epigenetic and stochastic factors to variation in gene expression
      have not been quantified in mammalian species. RESULTS: In this study we compared
      microarray-based measures of hepatic transcript abundance levels within and
      between five different strains of Mus musculus. Within each strain 23% to 44% of
      all genes exhibited statistically significant differences in expression between
      genetically identical individuals (positive false discovery rate of 10%). Genes
      functionally associated with cell growth, cytokine activity, amine metabolism,
      and ubiquitination were enriched in this group. Genetic divergence between
      individuals of different strains also contributed to transcript abundance level
      differences, but to a lesser extent than intra-strain variation, with
      approximately 3% of all genes exhibiting inter-strain expression differences.
      CONCLUSION: These results indicate that although DNA sequence fixes boundaries
      for gene expression variability, there remain considerable latitudes of
      expression within these genome-defined limits that have the potential to
      influence phenotypes. The extent of normal or expected natural variability in
      gene expression may provide an additional level of phenotypic opportunity for
      natural selection.

PMID- 16584537
TI  - Distinct yet linked: chaperone networks in the eukaryotic cytosol.
AB  - The terms chaperone and heat-shock protein are frequently used as synonyms, but
      this is an oversimplification. Although one subset of chaperones is induced by
      heat stress, a distinct group fails to respond in the same manner. Recent work
      reveals that this latter group is linked to the translational apparatus and
      functions in co-translational processes.

PMID- 16584535
TI  - Ranked prediction of p53 targets using hidden variable dynamic modeling.
AB  - Full exploitation of microarray data requires hidden information that cannot be
      extracted using current analysis methodologies. We present a new approach, hidden
      variable dynamic modeling (HVDM), which derives the hidden profile of a
      transcription factor from time series microarray data, and generates a ranked
      list of predicted targets. We applied HVDM to the p53 network, validating
      predictions experimentally using small interfering RNA. HVDM can be applied in
      many systems biology contexts to predict regulation of gene activity
      quantitatively.

PMID- 16584538
TI  - Partners in dicing.
AB  - Research into the mechanism of RNA interference has seen immense progress over
      the past few years. Recent studies of the protein Dicer, a key enzyme in the
      process, have started to reveal how this single enzyme is targeted to different
      RNA-silencing pathways.

PMID- 16584533
TI  - The semaphorins.
AB  - Semaphorins are secreted, transmembrane, and GPI-linked proteins, defined by
      cysteine-rich semaphorin protein domains, that have important roles in a variety
      of tissues. Humans have 20 semaphorins, Drosophila has five, and two are known
      from DNA viruses; semaphorins are also found in nematodes and crustaceans but not
      in non-animals. They are grouped into eight classes on the basis of phylogenetic
      tree analyses and the presence of additional protein motifs. The expression of
      semaphorins has been described most fully in the nervous system, but they are
      also present in most, or perhaps all, other tissues. Functionally, semaphorins
      were initially characterized for their importance in the development of the
      nervous system and in axonal guidance. More recently, they have been found to be
      important for the formation and functioning of the cardiovascular, endocrine,
      gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and
      respiratory systems. A common theme in the mechanisms of semaphorin function is
      that they alter the cytoskeleton and the organization of actin filaments and the
      microtubule network. These effects occur primarily through binding of semaphorins
      to their receptors, although transmembrane semaphorins also serve as receptors
      themselves. The best characterized receptors for mediating semaphorin signaling
      are members of the neuropilin and plexin families of transmembrane proteins.
      Plexins, in particular, are thought to control many of the functional effects of
      semaphorins; the molecular mechanisms of semaphorin signaling are still poorly
      understood, however. Given the importance of semaphorins in a wide range of
      functions, including neural connectivity, angiogenesis, immunoregulation, and
      cancer, much remains to be learned about these proteins and their roles in
      pathology and human disease.

PMID- 16584539
TI  - Type I insulin-like growth factor receptor over-expression induces proliferation
      and anti-apoptotic signaling in a three-dimensional culture model of breast
      epithelial cells.
AB  - INTRODUCTION: Activation of the type I insulin-like growth factor receptor
      (IGFIR) promotes proliferation and inhibits apoptosis in a variety of cell types.
      Transgenic mice expressing a constitutively active IGFIR or IGF-I develop mammary
      tumors and increased levels of IGFIR have been detected in primary breast
      cancers. However, the contribution of IGFIR activation in promoting breast cancer
      progression remains unknown. Mammary epithelial cell lines grown in three
      dimensional cultures form acinar structures that mimic the round, polarized,
      hollow and growth-arrested features of mammary alveoli. We used this system to
      determine how proliferation and survival signaling by IGFIR activation affects
      breast epithelial cell biology and contributes to breast cancer progression.
      METHODS: Pooled, stable MCF-10A breast epithelial cells expressing wild-type
      IGFIR or kinase-dead IGFIR (K1003A) were generated using retroviral-mediated gene
      transfer. The effects of over-expression of wild-type or kinase-dead IGFIR on
      breast epithelial cell biology were analyzed by confocal microscopy of three
      dimensional cultures. The contribution of signaling pathways downstream of IGFIR
      activation to proliferation and apoptosis were determined by pharmacological
      inhibition of phosphatidylinositol 3' kinase (PI3K) with LY294002, MAP kinase
      kinase (MEK) with UO126 and mammalian target of rapamycin (mTOR) with rapamycin.
      RESULTS: We found that MCF-10A cells over-expressing the IGFIR formed large,
      misshapen acinar structures with filled lumina and disrupted apico-basal
      polarization. This phenotype was ligand-dependent, occurring with IGF-I or
      supraphysiological doses of insulin, and did not occur in cells over-expressing
      the kinase-dead receptor. We observed increased proliferation, decreased
      apoptosis and increased phosphorylation of Ser473 of Akt and Ser2448 of mTOR
      throughout IGFIR structures. Inhibition of PI3K with LY294002 or MEK with UO126
      prevented the development of acinar structures from IGFIR-expressing but not
      control cells. The mTOR inhibitor rapamycin failed to prevent IGFIR-induced
      hyperproliferation and survival signaling. CONCLUSION: Increased proliferation
      and survival signaling as well as loss of apico-basal polarity by IGFIR
      activation in mammary epithelial cells may promote early lesions of breast
      cancer. Three-dimensional cultures of MCF-10A cells over-expressing the IGFIR are
      a useful model with which to study the role of IGFIR signaling in breast cancer
      progression and for characterizing the effects of chemotherapeutics targeted to
      IGFIR signaling.

PMID- 16584540
TI  - The action of selection on codon bias in the human genome is related to
      frequency, complexity, and chronology of amino acids.
AB  - BACKGROUND: The question of whether synonymous codon choice is affected by
      cellular tRNA abundance has been positively answered in many organisms. In some
      recent works, concerning the human genome, this relation has been studied, but no
      conclusive answers have been found. In the human genome, the variation in base
      composition and the absence of cellular tRNA count data makes the study of the
      question more complicated. In this work we study the relation between codon
      choice and tRNA abundance in the human genome by correcting relative codon usage
      for background base composition and using a measure based on tRNA-gene copy
      numbers as a rough estimate of tRNA abundance. RESULTS: We term major codons to
      be those codons with a relatively large tRNA-gene copy number for their
      corresponding amino acid. We use two measures of expression: breadth of
      expression (the number of tissues in which a gene was expressed) and maximum
      expression level among tissues (the highest value of expression of a gene among
      tissues). We show that for half the amino acids in the study (8 of 16) the
      relative major codon usage rises with breadth of expression. We show that these
      amino acids are significantly more frequent, are smaller and simpler, and are
      more ancient than the rest of the amino acids. Similar, although weaker, results
      were obtained for maximum expression level. CONCLUSION: There is evidence that
      codon bias in the human genome is related to selection, although the selection
      forces acting on codon bias may not be straightforward and may be different for
      different amino acids. We suggest that, in the first group of amino acids,
      selection acts to enhance translation efficiency in highly expressed genes by
      preferring major codons, and acts to reduce translation rate in lowly expressed
      genes by preferring non-major ones. In the second group of amino acids other
      selection forces, such as reducing misincorporation rate of expensive amino
      acids, in terms of their size/complexity, may be in action. The fact that codon
      usage is more strongly related to breadth of expression than to maximum
      expression level supports the notion, presented in a recent study, that codon
      choice may be related to the tRNA abundance in the tissue in which a gene is
      expressed.

PMID- 16584541
TI  - Acute health effects of the Tasman Spirit oil spill on residents of Karachi,
      Pakistan.
AB  - BACKGROUND: On July 27 2003, a ship carrying crude oil ran aground near Karachi
      and after two weeks released 37,000 tons of its cargo into the sea. Oil on the
      coastal areas and fumes in air raised health concerns among people. We assessed
      the immediate health impact of oil spill from the tanker Tasman Spirit on
      residents of the affected coastline in Karachi, Pakistan. METHODS: We conducted a
      study consisting of an exposed group including adults living in houses on the
      affected shoreline and two control groups (A and B) who lived at the distance of
      2 km and 20 km away from the sea, respectively. We selected households through
      systematic sampling and interviewed an adult male and female in each household
      about symptoms relating to eyes, respiratory tract, skin and nervous system,
      smoking, allergies, beliefs about the effect on their health and anxiety about
      the health effects. We used logistic regression procedures to model each symptom
      as an outcome and the exposure status as an independent variable while adjusting
      for confounders. We also used linear regression procedure to assess the
      relationship exposure status with symptoms score; calculated by summation of all
      symptoms. RESULTS: Overall 400 subjects were interviewed (exposed, n = 216; group
      A, n = 83; and group B, n = 101). The exposed group reported a higher occurrence
      of one or more symptoms compared to either of the control groups (exposed, 96%
      vs. group A, 70%, group B 85%; P < 0.001). Mean summary symptom scores were
      higher among the exposed group (14.5) than control group A (4.5) and control
      group B (3.8, P < 0.001). Logistic regression models indicated that there were
      statistically significant, moderate-to-strong associations (Prevalence ORs (POR)
      ranging from 2.3 to 37.0) between the exposed group and the symptoms. There was a
      trend of decreasing symptom-specific PORs with increase in distance from the
      spill site. Multiple linear regression model revealed strong relationship of
      exposure status with the symptoms score (beta = 8.24, 95% CI: 6.37-10.12).
      CONCLUSION: Results suggest that the occurrence of increased symptoms among the
      exposed group is more likely to be due to exposure to the crude oil spill.

PMID- 16584542
TI  - The potential role of dynamic thermal analysis in breast cancer detection.
AB  - BACKGROUND: It is presently well accepted that the breast exhibits a circadian
      rhythm reflective of its physiology. There is increasing evidence that rhythms
      associated with malignant cells proliferation are largely non-circadian. Cancer
      development appears to generate its own thermal signatures and the complexity of
      these signatures may be a reflection of its degree of development. The
      limitations of mammography as a screening modality especially in young women with
      dense breasts necessitated the development of novel and more effective screening
      strategies with a high sensitivity and specificity. The aim of this prospective
      study was to evaluate the feasibility of dynamic thermal analysis (DTA) as a
      potential breast cancer screening tool. METHODS: 173 women undergoing mammography
      as part of clinical assessment of their breast symptoms were recruited prior to
      having a biopsy. Thermal data from the breast surface were collected every five
      minutes for a period of 48 hours using eight thermal sensors placed on each
      breast surface [First Warning System (FWS), Lifeline Biotechnologies, Florida,
      USA]. Thermal data were recorded by microprocessors during the test period and
      analysed using specially developed statistical software. Temperature points from
      each contra-lateral sensor are plotted against each other to form a thermal
      motion picture of a lesion's physiological activity. DTA interpretations
      [positive (abnormal thermal signature) and negative (normal thermal signature)]
      were compared with mammography and final histology findings. RESULTS: 118 (68%)
      of participating patients, were found to have breast cancer on final histology.
      Mammography was diagnostic of malignancy (M5) in 55 (47%), indeterminate (M3, M4)
      in 54 (46%) and normal/benign (M1, M2) in 9 (8%) patients. DTA data was available
      on 160 (92.5%) participants. Using our initial algorithm, DTA was interpreted as
      positive in 113 patients and negative in 47 patients. Abnormal thermal signatures
      were found in 76 (72%) out of 105 breast cancer patients and 37 of the 55 benign
      cases. Then we developed a new algorithm using multiple-layer perception and
      SoftMax output artificial neural networks (ANN) on a subgroup (n = 38) of
      recorded files. The sensitivity improved to 76% (16/21) and false positives
      decreased to 26% (7/27) CONCLUSION: DTA of the breast is a feasible, non invasive
      approach that seems to be sensitive for the detection of breast cancer. However,
      the test has a limited specificity that can be improved further using ANN.
      Prospective multi-centre trials are required to validate this promising modality
      as an adjunct to screening mammography especially in young women with dense
      breasts.

PMID- 16584543
TI  - Outcome assessment of the VADO approach in psychiatric rehabilitation: a
      partially randomised multicentric trial.
AB  - BACKGROUND: Recent studies on representative samples of psychiatric services have
      shown that low proportions of cases received effective rehabilitation
      interventions. The following are likely to be the most important causes: the
      scarcity of mental health workers trained in social and work skills strategies
      and the absence of a structured framework to formulate rehabilitation practices.
      The aim of this study was to assess if a specific structured planning and
      evaluation manual, called VADO (Valutazione delle Abilita e Definizione degli
      Obiettivi--in english: Skills Assessment and Definition of Goals), is more
      effective than routine interventions in reducing disability in patients with
      schizophrenia. METHOD: Each of 10 mental health services were invited to recruit
      10 patients with a schizophrenic disorder. Altogether 98 patients were recruited.
      Of these, 62 patients were randomly allocated to the intervention/experimental or
      a control group. The remaining group of 36 patients was not randomised and it was
      considered as a parallel effectiveness study. Assessment measures at the
      beginning of the study and at the one-year follow-up included the FPS scale of
      social functioning and the BPRS 4.0. Between group (VADO vs. Routine) and time
      effects were examined with ANOVA, Chi-square or Fisher exact. Clinical
      "improvement" was defined as an increase of at least ten points on the FPS or a
      decrease of at least 20% on BPRS scores. RESULTS: 31 of the 62 randomized
      patients received the experimental interventions, while 31 followed the routine
      ones. At follow-up, the experimental group showed statistically and clinically
      greater improvements in psychopathology and social functioning. Better outcomes
      of both social functioning and symptom severity were observed in non randomised
      patients (parallel effectiveness study). CONCLUSION: The results suggest that
      setting personalised and measurable objectives, as recommended by the manual, can
      improve the outcome of rehabilitation of severe mental disorders. Better outcomes
      in the parallel effectiveness study could be attributed to the greater confidence
      and enthusiasm of staff in centres where the VADO approach originated.

PMID- 16584544
TI  - The effects of the Two-Week Rule on NHS colorectal cancer diagnostic services: a
      systematic literature review.
AB  - BACKGROUND: The Two-Week Rule (TWR) was introduced to ensure that all patients
      with a suspected colorectal cancer (CRC) saw a hospital specialist within 14 days
      of an urgent GP referral. Guidelines were available to GPs to facilitate the
      appropriate TWR referral of patients exhibiting high-risk CRC symptoms. METHODS:
      We aimed to evaluate the TWR and its CRC detection rate on NHS CRC diagnostic
      services by performing a literature search and critically appraising the peer
      reviewed studies. Only 12 studies were eligible for inclusion. Data was collected
      and overall results were given as weighted averages. RESULTS: The studies
      identified indicated that only 10.3% of patients referred by the TWR were
      eventually diagnosed with CRC. When examining the referral origin of all CRC
      patients diagnosed during the time of the studies, 24% had been referred using
      the TWR, 24.1% were referred as emergency cases, and 52.4% were referred using
      alternative routes. No evidence was found to indicate that the TWR had resulted
      in identifying CRC patients at an earlier, more treatable stage of their disease.
      CONCLUSION: The TWR referral system needs to be improved to increase the number
      of CRC patients referred using this fast track method as they present to their
      GP. The TWR and new NICE Guidelines for the referral of patients with suspected
      cancer should be independently evaluated.

PMID- 16584545
TI  - Exploiting the full power of temporal gene expression profiling through a new
      statistical test: application to the analysis of muscular dystrophy data.
AB  - BACKGROUND: The identification of biologically interesting genes in a temporal
      expression profiling dataset is challenging and complicated by high levels of
      experimental noise. Most statistical methods used in the literature do not fully
      exploit the temporal ordering in the dataset and are not suited to the case where
      temporal profiles are measured for a number of different biological conditions.
      We present a statistical test that makes explicit use of the temporal order in
      the data by fitting polynomial functions to the temporal profile of each gene and
      for each biological condition. A Hotelling T2-statistic is derived to detect the
      genes for which the parameters of these polynomials are significantly different
      from each other. RESULTS: We validate the temporal Hotelling T2-test on muscular
      gene expression data from four mouse strains which were profiled at different
      ages: dystrophin-, beta-sarcoglycan and gamma-sarcoglycan deficient mice, and
      wild-type mice. The first three are animal models for different muscular
      dystrophies. Extensive biological validation shows that the method is capable of
      finding genes with temporal profiles significantly different across the four
      strains, as well as identifying potential biomarkers for each form of the
      disease. The added value of the temporal test compared to an identical test which
      does not make use of temporal ordering is demonstrated via a simulation study,
      and through confirmation of the expression profiles from selected genes by
      quantitative PCR experiments. The proposed method maximises the detection of the
      biologically interesting genes, whilst minimising false detections. CONCLUSION:
      The temporal Hotelling T2-test is capable of finding relatively small and robust
      sets of genes that display different temporal profiles between the conditions of
      interest. The test is simple, it can be used on gene expression data generated
      from any experimental design and for any number of conditions, and it allows fast
      interpretation of the temporal behaviour of genes. The R code is available from
      V.V. The microarray data have been submitted to GEO under series GSE1574 and
      GSE3523.

PMID- 16584546
TI  - Economic evaluations of non-communicable disease interventions in developing
      countries: a critical review of the evidence base.
AB  - BACKGROUND: Demographic projections suggest a major increase in non-communicable
      disease (NCD) mortality over the next two decades in developing countries. In a
      climate of scarce resources, policy-makers need to know which interventions
      represent value for money. The prohibitive cost of performing multiple economic
      evaluations has generated interest in transferring the results of studies from
      one setting to another. This paper aims to bridge the gap in the current
      literature by critically evaluating the available published data on economic
      evaluations of NCD interventions in developing countries. METHODS: We identified
      and reviewed the methodological quality of 32 economic evaluations of NCD
      interventions in developing countries. Developing countries were defined
      according to the World Bank classification for low- and lower middle-income
      countries. We defined NCDs as the 12 categories listed in the 1993 World Bank
      report Investing in Health. English language literature was searched for the
      period January 1984 and January 2003 inclusive in Medline, Science Citation
      Index, HealthStar, NHS Economic Evaluation Database and Embase using medical
      subheading terms and free text searches. We then assessed the quality of studies
      according to a set of pre-defined technical criteria. RESULTS: We found that the
      quality of studies was poor and resource allocation decisions made by local and
      global policy-makers on the basis of this evidence could be misleading.
      Furthermore we have identified some clear gaps in the literature, particularly
      around injuries and strategies for tackling the consequences of the emerging
      tobacco epidemic. CONCLUSION: In the face of poor evidence the role of so-called
      generalised cost-effectiveness analyses has an important role to play in aiding
      public health decision-making at the global level. Further research is needed to
      investigates the causes of variation among cost, effects and cost-effectiveness
      data within and between settings. Such analyses still need to take a broad view,
      present data in a transparent manner and take account of local constraints.

PMID- 16584547
TI  - Wild Allium species (Alliaceae) used in folk medicine of Tajikistan and
      Uzbekistan.
AB  - BACKGROUND: Hitherto available sources from literature mentioned several wild
      growing Allium species as "edible" or "medicinally used" but without any further
      specification. METHODS: New data were gained during recent research missions:
      Allium plants were collected and shown to the local population which was asked
      for names and usage of these plants. RESULTS: Information was collected about
      current medical applications of sixteen wild species, nine of which belong to
      different sections of Allium subgenus Melanocrommyum. These plants are used
      against headache, cold, and stomach problems, and are mostly applied fresh or
      after boiling. CONCLUSION: Close taxonomic relatives of the common onion were
      used similar to cultivated onion species, but medical use like garlic was mostly
      reported for species taxonomically not related to garlic.

PMID- 16584548
TI  - High frequency oscillatory ventilation and prone positioning in a porcine model
      of lavage-induced acute lung injury.
AB  - BACKGROUND: This animal study was conducted to assess the combined effects of
      high frequency oscillatory ventilation (HFOV) and prone positioning on pulmonary
      gas exchange and hemodynamics. METHODS: Saline lung lavage was performed in 14
      healthy pigs (54 +/- 3.1 kg, mean +/- SD) until the arterial oxygen partial
      pressure (PaO2) decreased to 55 +/- 7 mmHg. The animals were ventilated in the
      pressure controlled mode (PCV) with a positive endexpiratory pressure (PEEP) of 5
      cmH2O and a tidal volume (VT) of 6 ml/kg body weight. After a stabilisation
      period of 60 minutes, the animals were randomly assigned to 2 groups. Group 1:
      HFOV in supine position; group 2: HFOV in prone position. After evaluation of
      prone positioning in group 2, the mean airway pressure (Pmean) was increased by 3
      cmH2O from 16 to 34 cmH2O every 20 minutes in both groups accompanied by
      measurements of respiratory and hemodynamic variables. Finally all animals were
      ventilated supine with PCV, PEEP = 5 cm H2O, VT = 6 ml/kg. RESULTS: Combination
      of HFOV with prone positioning improves oxygenation and results in normalisation
      of cardiac output and considerable reduction of pulmonary shunt fraction at a
      significant (p < 0.05) lower Pmean than HFOV and supine positioning. CONCLUSION:
      If ventilator induced lung injury is ameliorated by a lower Pmean, a combined
      treatment approach using HFOV and prone positioning might result in further lung
      protection.

PMID- 16584551
TI  - Sclerosing lobular hyperplasia of breast: cytomorphologic and histomorphologic
      features: a case report.
AB  - BACKGROUND: Mammary sclerosing lobular hyperplasia is an uncommon benign lesion
      of adolescent and young women. Fine-needle aspiration cytology of mammary
      sclerosing lobular hyperplasia is said to show characteristic features that
      include an absence of stromal fragments. CASE PRESENTATION: In this article, we
      describe a case of sclerosing lobular hyperplasia that occurred in the right
      breast of a 12-year-old girl. Fine-needle aspiration cytology showed some
      fibroadenoma-like features including the presence of stromal fragments, while
      branched tubular fragments were not seen. The diagnosis of sclerosing lobular
      hyperplasia was made on histologic examination that showed preserved acinar
      architecture with lobular hyperplasia and sclerosis of intralobular and
      interlobular stroma. CONCLUSION: Fine-needle aspiration cytology features of
      mammary sclerosing lobular hyperplasia are not diagnostic and overlap with those
      of fibroadenoma; however, a distinction between the two benign entities is of no
      clinical significance. The definitive diagnosis of sclerosing lobular hyperplasia
      requires histopathologic evaluation.

PMID- 16584549
TI  - Multi-level gene expression profiles affected by thymidylate synthase and 5
      fluorouracil in colon cancer.
AB  - BACKGROUND: Thymidylate synthase (TS) is a critical target for cancer
      chemotherapy and is one of the most extensively studied biomarkers for
      fluoropyrimidine-based chemotherapy. In addition to its critical role in enzyme
      catalysis, TS functions as an RNA binding protein to regulate the expression of
      its own mRNA translation and other cellular mRNAs, such as p53, at the
      translational level. In this study, a comprehensive gene expression analysis at
      the levels of both transcriptional and post-transcriptional regulation was
      conducted to identify response markers using human genome array with TS-depleted
      human colon cancer HCT-C18 (TS-) cells and HCT-C18 (TS+) cells stably transfected
      with the human TS cDNA expression plasmid. RESULTS: A total of 38 genes were
      found to be significantly affected by TS based on the expression profiles of
      steady state mRNA transcripts. However, based on the expression profiles of
      polysome associated mRNA transcripts, over 149 genes were affected by TS
      overexpression. This indicates that additional post-transcriptionally controlled
      genes can be captured with profiling polysome associated mRNA population. This
      unique approach provides a comprehensive overview of genes affected by TS.
      Additional novel post-transcriptionally regulated genes affected by 5
      fluorouracil (5-FU) treatment were also discovered via similar approach.
      CONCLUSION: To our knowledge, this is the first time that a comprehensive gene
      expression profile regulated by TS and 5-FU was analyzed at the multiple steps of
      gene regulation. This study will provide candidate markers that can be
      potentially used for predicting therapeutic outcomes for fluoropyrimidine-based
      cancer chemotherapy.

PMID- 16584550
TI  - Use of physiological constraints to identify quantitative design principles for
      gene expression in yeast adaptation to heat shock.
AB  - BACKGROUND: Understanding the relationship between gene expression changes,
      enzyme activity shifts, and the corresponding physiological adaptive response of
      organisms to environmental cues is crucial in explaining how cells cope with
      stress. For example, adaptation of yeast to heat shock involves a characteristic
      profile of changes to the expression levels of genes coding for enzymes of the
      glycolytic pathway and some of its branches. The experimental determination of
      changes in gene expression profiles provides a descriptive picture of the
      adaptive response to stress. However, it does not explain why a particular
      profile is selected for any given response. RESULTS: We used mathematical models
      and analysis of in silico gene expression profiles (GEPs) to understand how
      changes in gene expression correlate to an efficient response of yeast cells to
      heat shock. An exhaustive set of GEPs, matched with the corresponding set of
      enzyme activities, was simulated and analyzed. The effectiveness of each profile
      in the response to heat shock was evaluated according to relevant physiological
      and functional criteria. The small subset of GEPs that lead to effective
      physiological responses after heat shock was identified as the result of the
      tuning of several evolutionary criteria. The experimentally observed
      transcriptional changes in response to heat shock belong to this set and can be
      explained by quantitative design principles at the physiological level that
      ultimately constrain changes in gene expression. CONCLUSION: Our theoretical
      approach suggests a method for understanding the combined effect of changes in
      the expression of multiple genes on the activity of metabolic pathways, and
      consequently on the adaptation of cellular metabolism to heat shock. This method
      identifies quantitative design principles that facilitate understating the
      response of the cell to stress.

PMID- 16584552
TI  - Conceptual biology, hypothesis discovery, and text mining: Swanson's legacy.
AB  - Innovative biomedical librarians and information specialists who want to expand
      their roles as expert searchers need to know about profound changes in biology
      and parallel trends in text mining. In recent years, conceptual biology has
      emerged as a complement to empirical biology. This is partly in response to the
      availability of massive digital resources such as the network of databases for
      molecular biologists at the National Center for Biotechnology Information.
      Developments in text mining and hypothesis discovery systems based on the early
      work of Swanson, a mathematician and information scientist, are coincident with
      the emergence of conceptual biology. Very little has been written to introduce
      biomedical digital librarians to these new trends. In this paper, background for
      data and text mining, as well as for knowledge discovery in databases (KDD) and
      in text (KDT) is presented, then a brief review of Swanson's ideas, followed by a
      discussion of recent approaches to hypothesis discovery and testing. 'Testing' in
      the context of text mining involves partially automated methods for finding
      evidence in the literature to support hypothetical relationships. Concluding
      remarks follow regarding (a) the limits of current strategies for evaluation of
      hypothesis discovery systems and (b) the role of literature-based discovery in
      concert with empirical research. Report of an informatics-driven literature
      review for biomarkers of systemic lupus erythematosus is mentioned. Swanson's
      vision of the hidden value in the literature of science and, by extension, in
      biomedical digital databases, is still remarkably generative for information
      scientists, biologists, and physicians.

PMID- 16584553
TI  - The Safety Attitudes Questionnaire: psychometric properties, benchmarking data,
      and emerging research.
AB  - BACKGROUND: There is widespread interest in measuring healthcare provider
      attitudes about issues relevant to patient safety (often called safety climate or
      safety culture). Here we report the psychometric properties, establish
      benchmarking data, and discuss emerging areas of research with the University of
      Texas Safety Attitudes Questionnaire. METHODS: Six cross-sectional surveys of
      health care providers (n = 10,843) in 203 clinical areas (including critical care
      units, operating rooms, inpatient settings, and ambulatory clinics) in three
      countries (USA, UK, New Zealand). Multilevel factor analyses yielded results at
      the clinical area level and the respondent nested within clinical area level. We
      report scale reliability, floor/ceiling effects, item factor loadings, inter
      factor correlations, and percentage of respondents who agree with each item and
      scale. RESULTS: A six factor model of provider attitudes fit to the data at both
      the clinical area and respondent nested within clinical area levels. The factors
      were: Teamwork Climate, Safety Climate, Perceptions of Management, Job
      Satisfaction, Working Conditions, and Stress Recognition. Scale reliability was
      0.9. Provider attitudes varied greatly both within and among organizations.
      Results are presented to allow benchmarking among organizations and emerging
      research is discussed. CONCLUSION: The Safety Attitudes Questionnaire
      demonstrated good psychometric properties. Healthcare organizations can use the
      survey to measure caregiver attitudes about six patient safety-related domains,
      to compare themselves with other organizations, to prompt interventions to
      improve safety attitudes and to measure the effectiveness of these interventions.

PMID- 16584554
TI  - An epidemiological study on anemia among institutionalized people with
      intellectual and/or motor disability with special reference to its frequency,
      severity and predictors.
AB  - BACKGROUND: To examine the type, frequency, severity, and predictors of anemia
      and its relationship with co-morbid conditions among institutionalized people
      with intellectual and/or motor disability. METHODS: We conducted a cross
      sectional study at a public facility for people with intellectual and/or motor
      disability in Ibaraki prefecture, Japan. Health checkup data obtained in 2001
      from 477 people with intellectual disability (male: 286, average age 40.6 +/-
      12.3; female: 191, average age 45.1 +/- 11.6) were retrospectively reviewed.
      RESULTS: The prevalence of anemia among male participants was higher than in
      female participants for each disability category (intellectual disability, 41.1%,
      4.2%; cerebral palsy, 37.5%, 4.8%; Down's syndrome, 15.0%, 0%; severe motor and
      intellectual disabilities, 61.9%, 16.7%). Most participants with anemia (93.8 -
      100%) showed a normocytic normochromic anemia pattern. Multivariate analysis
      revealed that factors related to an increase in frequency included sex (male),
      low body mass index (BMI), use of anticonvulsants or major tranquilizers, and a
      high zinc sulfate turbidity test (ZTT) value. No clinically diagnosed co-morbid
      condition was found to be related to the presence of anemia. CONCLUSION: A high
      frequency of mild normocytic normochromic anemia in institutionalized people with
      intellectual and/or motor disability was observed, particularly among males.
      Medications and chronic inflammation may increase the risk of anemia.

PMID- 16584555
TI  - Long-term culture of cholangiocytes from liver fibro-granulomatous lesions.
AB  - BACKGROUND: Extensive bile duct proliferation is a key feature of the tissue
      reaction to clinical and experimental forms of liver injury. Experimental
      infection of mice by Schistosoma mansoni is a well-studied model of liver
      fibrosis with bile duct hyperplasia. However, the regulatory mechanisms of bile
      duct changes are not well understood. In this study we report the reproducible
      isolation of long-term cultures of cholangiocytes from mice livers with
      schistosomal fibrosis. METHODS: We have isolated a cholangiocyte cell line from
      Schistosoma-induced liver granulomas using a combination of methods including
      selective adhesion and isopyknic centrifugation in Percoll. RESULTS: The cell
      line was characterized by morphological criteria in optical and transmission
      electron microscopy, ability to form well differentiated ductular structures in
      collagen gels and by a positive staining for cytokeratin 18 and cytokeratin 19.
      To our knowledge, this is the first murine cholangiocyte cell line isolated from
      schistosomal fibrosis reported in the literature. CONCLUSION: After 9 months and
      16 passages this diploid cell line maintained differentiated characteristics and
      a high proliferative capacity. We believe the method described here may be a
      valuable tool to study bile duct changes during hepatic injury.

PMID- 16584556
TI  - Open cholecystectomy for all patients in the era of laparoscopic surgery - a
      prospective cohort study.
AB  - BACKGROUND: Open cholecystectomy through a small incision is an alternative to
      laparoscopic cholecystectomy. METHODS: From 1 January 2002 through 31 December
      2003, all operations upon the gallbladder in a district hospital with emergency
      admission and responsibility for surgical training were done as intended small
      incision open cholecystectomy. RESULTS: 182 women and 90 men with a median age of
      56 (interquartile range 45 to 68 years) underwent cholecystectomy for symptomatic
      gallbladder disease, 170 as elective and 102 as emergency cases. Trainee surgeons
      assisted by consultants or registrars having passed an examination for open
      cholecystectomy performed surgery in 194 cases (71%). The common bile duct was
      explored in 52 patients. Total postoperative morbidity was six percent. Median
      postoperative stay was one day and mean total (pre- and postoperative) hospital
      stay 3.1 days. 32 operations (12%) were done as day surgery procedures.
      Nationally in Sweden in 2002, mean total hospital stay was 4.4 days, and 13% of
      all cholecystectomies were performed on an outpatient basis. CONCLUSION: Open,
      small-incision cholecystectomy for all patients is compatible with short hospital
      stay, evidence-based gall-bladder surgery, and training of surgical residents.

PMID- 16584557
TI  - Linking community pharmacy dispensing data to prescribing data of general
      practitioners.
AB  - BACKGROUND: Databases are frequently used for pharmacoepidemiological research.
      However, most of these databases consist either of prescribing, dispensing or
      administrative data and therefore lack insight in the interaction between the
      several health professionals around the patient. METHODS: To determine the
      success rate of linking records from the dispensing database of the Foundation
      for Pharmaceutical Statistics to the prescribing database of the second Dutch
      national survey of general practice, conducted by NIVEL (Netherlands Institute
      for Health Services Research), a deterministic record linkage approach was used
      with patient and prescription characteristics as matching variables between the
      two databases. RESULTS: The catchment area included 123 community pharmacies, 90
      GP practices and approximately 170,000 unique patients. Overall 110,102 (64.8%)
      unique patients were linked using the matching variables patient's gender, year
      of birth, the 4-digit part of the postal code, date of dispensing/prescribing and
      ATC-code. The final database contains of the 110,102 both prescribing data from
      83 GP practices and dispensing data of 112 community pharmacies. CONCLUSION: This
      study shows that linkage of dispensing to prescribing data is feasible with a
      combination of patient characteristics, such as gender, year of birth and postal
      code, and prescription characteristics like prescription date and ATC-code. We
      obtained a linkage proportion of 64.8% resulting in complete prescribing and
      dispensing history of 110,102 patients. This offers an opportunity to gain
      insight in the mechanisms and factors influencing drug utilisation in general
      practice.

PMID- 16584558
TI  - Insertional protein engineering for analytical molecular sensing.
AB  - The quantitative detection of low analyte concentrations in complex samples is
      becoming an urgent need in biomedical, food and environmental fields. Biosensors,
      being hybrid devices composed by a biological receptor and a signal transducer,
      represent valuable alternatives to non biological analytical instruments because
      of the high specificity of the biomolecular recognition. The vast range of
      existing protein ligands enable those macromolecules to be used as efficient
      receptors to cover a diversity of applications. In addition, appropriate protein
      engineering approaches enable further improvement of the receptor functioning
      such as enhancing affinity or specificity in the ligand binding. Recently,
      several protein-only sensors are being developed, in which either both the
      receptor and signal transducer are parts of the same protein, or that use the
      whole cell where the protein is produced as transducer. In both cases, as no
      further chemical coupling is required, the production process is very convenient.
      However, protein platforms, being rather rigid, restrict the proper signal
      transduction that necessarily occurs through ligand-induced conformational
      changes. In this context, insertional protein engineering offers the possibility
      to develop new devices, efficiently responding to ligand interaction by dramatic
      conformational changes, in which the specificity and magnitude of the sensing
      response can be adjusted up to a convenient level for specific analyte species.
      In this report we will discuss the major engineering approaches taken for the
      designing of such instruments as well as the relevant examples of resulting
      protein-only biosensors.

PMID- 16584559
TI  - Transesophageal echocardiographic evaluation of an intraoperative retrograde
      acute aortic dissection: case report.
AB  - BACKGROUND: We report an intraoperative retrograde dissection of the aorta and
      its subsequent evaluation by transesophageal echocardiography (TEE). CASE
      PRESENTATION: A 78 year old woman with an ascending aortic aneurysm without
      dissection and coronary artery disease was brought to the operating room for
      aneurysm repair and coronary artery bypass grafting. After initiation of
      cardiopulmonary bypass through a femoral artery cannula, aortic dissection was
      noted and subsequently imaged by TEE. CONCLUSION: Retrograde aortic dissection
      through the femoral artery is life-threatening. Intraoperative TEE can be used to
      diagnose this uncommon event, and should be considered after initiation of
      bypass.

PMID- 16584560
TI  - Differentiation of myomas by means of biomagnetic and doppler findings.
AB  - AIM: To elucidate the hemodynamics of the uterine artery myomas by use of Doppler
      ultrasound and biomagnetic measurements. METHOD: Twenty-four women were included
      in the study. Sixteen of them were characterised with large myomas whereas 8 of
      them with small ones. Biomagnetic signals of uterine arteries myomas were
      recorded and analyzed with Fourier analysis. The biomagnetic signals were
      distributed according to spectral amplitudes as high (140-300 ft/ radicalHz), low
      (50-110 ft/ radicalHz) and borderline (111-139 ft/ radicalHz). Uterine artery
      waveform measurements were evaluated by use of Pulsatility Index (PI) (normal
      value PI < 1.45). RESULTS: There was a statistically significant difference
      between large and small myomas concerning the waveform amplitudes (P < 0.0005)
      and the PI index (P < 0.0005). Specifically, we noticed high biomagnetic
      amplitudes in most large myomas (93.75 %) and low biomagnetic amplitudes in most
      small ones (87.5 %). CONCLUSION: It is suggested that the biomagnetic recordings
      of uterine artery myomas could be a valuable modality in the estimation of the
      circulation of blood cells justifying the findings of Doppler velocimetry
      examination.

PMID- 16584561
TI  - Role of CD8+ cells in controlling replication of nonpathogenic Simian
      Immunodeficiency Virus SIVmac1A11.
AB  - Infection of macaques with the avirulent molecular clone SIVmac1A11 results in
      transient low viremia and no disease. To investigate if this low viremia is
      solely due to intrinsic poor replication fitness or is mediated by efficient
      immune-mediated control, 5 macaques were inoculated intravenously with
      SIVmac1A11. Three animals that were depleted of CD8+ cells at the start of
      infection had more prolonged viremia with peak virus levels 1 to 2 logs higher
      than those of 2 animals that received a non-depleting control antibody. Thus,
      CD8+ cell-mediated immune responses play an important role in controlling
      SIVmac1A11 replication during acute viremia.

PMID- 16584562
TI  - A ketogenic diet as a potential novel therapeutic intervention in amyotrophic
      lateral sclerosis.
AB  - BACKGROUND: The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is
      uncertain but mitochondrial dysfunction may play an important role. Ketones
      promote mitochondrial energy production and membrane stabilization. RESULTS: SOD1
      G93A transgenic ALS mice were fed a ketogenic diet (KD) based on known
      formulations for humans. Motor performance, longevity, and motor neuron counts
      were measured in treated and disease controls. Because mitochondrial dysfunction
      plays a central role in neuronal cell death in ALS, we also studied the effect
      that the principal ketone body, D-beta-3 hydroxybutyrate (DBH), has on
      mitochondrial ATP generation and neuroprotection. Blood ketones were > 3.5 times
      higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline
      motor performance 25 days later than disease controls. KD animals weighed 4.6 g
      more than disease control animals at study endpoint; the interaction between diet
      and change in weight was significant (p = 0.047). In spinal cord sections
      obtained at the study endpoint, there were more motor neurons in KD fed animals
      (p = 0.030). DBH prevented rotenone mediated inhibition of mitochondrial complex
      I but not malonate inhibition of complex II. Rotenone neurotoxicity in SMI-32
      immunopositive motor neurons was also inhibited by DBH. CONCLUSION: This is the
      first study showing that diet, specifically a KD, alters the progression of the
      clinical and biological manifestations of the G93A SOD1 transgenic mouse model of
      ALS. These effects may be due to the ability of ketone bodies to promote ATP
      synthesis and bypass inhibition of complex I in the mitochondrial respiratory
      chain.

PMID- 16584563
TI  - Ebbie: automated analysis and storage of small RNA cloning data using a dynamic
      web server.
AB  - BACKGROUND: DNA sequencing is used ubiquitously: from deciphering genomes to
      determining the primary sequence of small RNAs (smRNAs). The cloning of smRNAs is
      currently the most conventional method to determine the actual sequence of these
      important regulators of gene expression. Typical smRNA cloning projects involve
      the sequencing of hundreds to thousands of smRNA clones that are delimited at
      their 5' and 3' ends by fixed sequence regions. These primers result from the
      biochemical protocol used to isolate and convert the smRNA into clonable PCR
      products. Recently we completed a smRNA cloning project involving tobacco plants,
      where analysis was required for approximately 700 smRNA sequences. Finding no
      easily accessible research tool to enter and analyze smRNA sequences we developed
      Ebbie to assist us with our study. RESULTS: Ebbie is a semi-automated smRNA
      cloning data processing algorithm, which initially searches for any substring
      within a DNA sequencing text file, which is flanked by two constant strings. The
      substring, also termed smRNA or insert, is stored in a MySQL and BlastN database.
      These inserts are then compared using BlastN to locally installed databases
      allowing the rapid comparison of the insert to both the growing smRNA database
      and to other static sequence databases. Our laboratory used Ebbie to analyze
      scores of DNA sequencing data originating from an smRNA cloning project. Through
      its built-in instant analysis of all inserts using BlastN, we were able to
      quickly identify 33 groups of smRNAs from approximately 700 database entries.
      This clustering allowed the easy identification of novel and highly expressed
      clusters of smRNAs. Ebbie is available under GNU GPL and currently implemented on
      http://bioinformatics.org/ebbie/. CONCLUSION: Ebbie was designed for medium sized
      smRNA cloning projects with about 1,000 database entries. Ebbie can be used for
      any type of sequence analysis where two constant primer regions flank a sequence
      of interest. The reliable storage of inserts, and their annotation in a MySQL
      database, BlastN comparison of new inserts to dynamic and static databases make
      it a powerful new tool in any laboratory using DNA sequencing. Ebbie also
      prevents manual mistakes during the excision process and speeds up annotation and
      data-entry. Once the server is installed locally, its access can be restricted to
      protect sensitive new DNA sequencing data. Ebbie was primarily designed for smRNA
      cloning projects, but can be applied to a variety of RNA and DNA cloning
      projects.

PMID- 16584564
TI  - Activation of protein kinase C in the spinal cord produces mechanical
      hyperalgesia by activating glutamate receptors, but does not mediate chronic
      muscle-induced hyperalgesia.
AB  - BACKGROUND: Protein kinase C (PKC) in the spinal cord appears to mediate chronic
      injury-induced pain, but not acute nociceptive pain. Muscle insult results in
      increased release of glutamate spinally, and hyperalgesia that is reversed by
      spinal blockade of NMDA and non-NMDA glutamate receptors. Therefore, we
      hypothesized that spinal activation of PKC 1) mediates the late phase of
      hyperalgesia 1 week after muscle insult, and 2) produces mechanical hyperalgesia
      through activation of NMDA and non-NMDA glutamate receptors. RESULTS: Rats were
      implanted with intrathecal catheters for delivery of drugs directly to the spinal
      cord. Mechanical withdrawal thresholds of the paw were determined using von Frey
      filaments. Intrathecal phorbol 12,13 dibutyrate (PDBu) produced a dose-dependent
      decrease in the mechanical withdrawal threshold of the paw that was prevented by
      pretreatment with the PKC inhibitor, GF109203X. Pretreatment with an NMDA
      receptor antagonist (AP5) or a AMPA/kainate receptor antagonist (NBQX) prevented
      the decrease in mechanical withdrawal threshold by PDBu. Two injections of acidic
      saline in the gastrocnemius muscle decreased the mechanical withdrawal thresholds
      of the paw bilaterally 24 h and 1 week after the second injection. However,
      blockade PKC in the spinal cord had no effect on the decreased withdrawal
      thresholds of the paw when compared to vehicle controls. CONCLUSION: Spinal
      activation of PKC produces mechanical hyperalgesia of the paw that depends on
      activation of NMDA and non-NMDA receptors. Chronic muscle-induced mechanical
      hyperalgesia, on the other hand, does not utilize spinal PKC.

PMID- 16584565
TI  - Measuring change in activities of daily living in nursing home residents with
      moderate to severe cognitive impairment.
AB  - BACKGROUND: The objective of this study was to assess the responsiveness of the
      Minimum Data Set Activities of Daily Living (MDS-ADL) Scale to change over time
      by examining the change in physical function in adults with moderate to severe
      dementia with no comorbid illness who had been resident in a nursing home for
      over 90 days. METHODS: Longitudinal data were collected on nursing home residents
      with moderate (n = 7001) or severe (n = 4616) dementia in one US state from the
      US national Minimum Data Set (MDS). Severity of dementia was determined by the
      MDS Cognitive Performance Scale (CPS). Physical function was assessed by summing
      the seven items (bed mobility, transfer, locomotion, dressing, eating, toilet
      use, personal hygiene) on the MDS activities of daily living (ADL) Long Form
      scale. Mean change over time of MDS-ADL scores were estimated at three and six
      months for residents with moderate (CPS score of 3) and severe (CPS score of 4 or
      5) dementia. RESULTS: Physical function in residents with moderate cognitive
      impairment deteriorated over six months by an average of 1.78 points on the MDS
      ADL Long Form scale, while those with severe cognitive impairment declined by an
      average of 1.70 points. Approximately one quarter of residents in both groups
      showed some improvement in physical function over the six month period. Residents
      with moderate cognitive impairment experienced the greatest deterioration in
      early-loss and mid-loss ADL items (personal hygiene, dressing, toilet use) and
      residents with severe cognitive impairment showed the greatest deterioration in
      activities related to eating, a late loss ADL. CONCLUSION: The MDS-ADL Long Form
      scale detected clinically meaningful change in physical function in a large
      cohort of long-stay nursing home residents with moderate to severe dementia,
      supporting its use as a research tool in future studies.

PMID- 16584567
TI  - The use of the 1 mm laparoscope to assist in port insertion in pelvic oncological
      surgery.
AB  - BACKGROUND: A 1 mm minilaparoscope (Lifeline Biotechnoligies, Florida, USA) was
      assessed for aiding port site insertions. METHODS: Ten consecutive patients
      having laparoscopic procedures in a gynaecological oncology unit were included.
      Minilaparoscopy was feasible in all cases and was used to insert the umbilical
      port under direct vision in all patients. In one case, a thick band of abdominal
      adhesions was identified and a further lateral port site was inserted to aid
      their dissection. RESULTS: The minilaparoscope correctly identified all 10
      patients with peritoneal disease and identified all patients who were suitable
      for debulking procedures. CONCLUSION: Minilaparoscopy with the 1 mm endoscope
      appears to be safe and accurate and we feel that it has a place in helping the
      surgeon identify adhesions and peritoneal disease as well as assisting further
      port site insertion safely and with minimal complications.

PMID- 16584566
TI  - Quantitative elementary mode analysis of metabolic pathways: the example of yeast
      glycolysis.
AB  - BACKGROUND: Elementary mode analysis of metabolic pathways has proven to be a
      valuable tool for assessing the properties and functions of biochemical systems.
      However, little comprehension of how individual elementary modes are used in real
      cellular states has been achieved so far. A quantitative measure of fluxes
      carried by individual elementary modes is of great help to identify dominant
      metabolic processes, and to understand how these processes are redistributed in
      biological cells in response to changes in environmental conditions, enzyme
      kinetics, or chemical concentrations. RESULTS: Selecting a valid decomposition of
      a flux distribution onto a set of elementary modes is not straightforward, since
      there is usually an infinite number of possible such decompositions. We first
      show that two recently introduced decompositions are very closely related and
      assign the same fluxes to reversible elementary modes. Then, we show how such
      decompositions can be used in combination with kinetic modelling to assess the
      effects of changes in enzyme kinetics on the usage of individual metabolic
      routes, and to analyse the range of attainable states in a metabolic system. This
      approach is illustrated by the example of yeast glycolysis. Our results indicate
      that only a small subset of the space of stoichiometrically feasible steady
      states is actually reached by the glycolysis system, even when large variation
      intervals are allowed for all kinetic parameters of the model. Among eight
      possible elementary modes, the standard glycolytic route remains dominant in all
      cases, and only one other elementary mode is able to gain significant flux values
      in steady state. CONCLUSION: These results indicate that a combination of
      structural and kinetic modelling significantly constrains the range of possible
      behaviours of a metabolic system. All elementary modes are not equal contributors
      to physiological cellular states, and this approach may open a direction toward a
      broader identification of physiologically relevant elementary modes among the
      very large number of stoichiometrically possible modes.

PMID- 16584568
TI  - Method of predicting splice sites based on signal interactions.
AB  - BACKGROUND: Predicting and proper ranking of canonical splice sites (SSs) is a
      challenging problem in bioinformatics and machine learning communities. Any
      progress in SSs recognition will lead to better understanding of splicing
      mechanism. We introduce several new approaches of combining a priori knowledge
      for improved SS detection. First, we design our new Bayesian SS sensor based on
      oligonucleotide counting. To further enhance prediction quality, we applied our
      new de novo motif detection tool MHMMotif to intronic ends and exons. We combine
      elements found with sensor information using Naive Bayesian Network, as
      implemented in our new tool SpliceScan. RESULTS: According to our tests, the
      Bayesian sensor outperforms the contemporary Maximum Entropy sensor for 5' SS
      detection. We report a number of putative Exonic (ESE) and Intronic (ISE)
      Splicing Enhancers found by MHMMotif tool. T-test statistics on mouse/rat
      intronic alignments indicates, that detected elements are on average more
      conserved as compared to other oligos, which supports our assumption of their
      functional importance. The tool has been shown to outperform the SpliceView,
      GeneSplicer, NNSplice, Genio and NetUTR tools for the test set of human genes.
      SpliceScan outperforms all contemporary ab initio gene structural prediction
      tools on the set of 5' UTR gene fragments. CONCLUSION: Designed methods have many
      attractive properties, compared to existing approaches. Bayesian sensor, MHMMotif
      program and SpliceScan tools are freely available on our web site. REVIEWERS:
      This article was reviewed by Manyuan Long, Arcady Mushegian and Mikhail Gelfand.

PMID- 16584570
TI  - Adult clear cell sarcoma of the kidney: a case report.
AB  - BACKGROUND: Clear cell sarcoma of the kidney (CCSK) in adults is extremely rare.
      Optimal treatment of adult patients with CCSK remains unclear. CASE PRESENTATION:
      A 22-year-old man presented with a 2-month history of left flank pain. A color
      duplex sonography revealed a hypervascular, heterogeneous renal mass. Abdominal
      and pelvic computerized tomography showed a heterogeneous mass originating from
      the lower pole of the left kidney and infiltrating to the psoas muscle. Further
      evaluation including bone scan did not demonstrate any evidence of metastases. A
      left radical nephrectomy with hilar lymphadenectomy through an intraperitoneal
      approach with an anterior subcostal incision was performed. The histopathological
      diagnosis of the mass was a clear cell sarcoma of the kidney. No lymph node
      metastases were found. Concomitant chemo-radiotherapy was performed. Therapy
      related serious side effects were not observed. There was no evidence of local
      recurrence or metastases during the following twenty-four months after therapy.
      CONCLUSION: We believe that the combination therapy is efficacious for preventing
      the local recurrence and distant metastases. Accurate diagnosis is very important
      and therapy must also include doxorubicin regardless of the disease stage in
      adult patients with CCSK.

PMID- 16584569
TI  - Current trends in the management of extra-abdominal desmoid tumours.
AB  - Extra-abdominal desmoid tumours are slow-growing, histologically benign tumours
      of fibroblastic origin with variable biologic behaviour. They are locally
      aggressive and invasive to surrounding anatomic structures. Magnetic resonance
      imaging is the modality of choice for the diagnosis and the evaluation of the
      tumours. Current management of desmoids involves a multidisciplinary approach.
      Wide margin surgical resection remains the main treatment modality for local
      control of the tumour. Amputation should not be the initial treatment, and
      function-preserving procedures should be the primary treatment goal. Adjuvant
      radiation therapy is recommended both for primary and recurrent lesions.
      Chemotherapy may be used for recurrent or unresectable disease. Overall local
      recurrence rates vary and depend on patient's age, tumour location and margins at
      resection.

PMID- 16584571
TI  - Organizational aspects and implementation of data systems in large-scale
      epidemiological studies in less developed countries.
AB  - BACKGROUND: In the conduct of epidemiological studies in less developed
      countries, while great emphasis is placed on study design, data collection, and
      analysis, often little attention is paid to data management. As a consequence,
      investigators working in these countries frequently face challenges in cleaning,
      analyzing and interpreting data. In most research settings, the data management
      team is formed with temporary and unskilled persons. A proper working environment
      and training or guidance in constructing a reliable database is rarely available.
      There is little information available that describes data management problems and
      solutions to those problems. Usually a line or two can be obtained in the methods
      section of research papers stating that the data are doubly-entered and that
      outliers and inconsistencies were removed from the data. Such information
      provides little assurance that the data are reliable. There are several issues in
      data management that if not properly practiced may create an unreliable database,
      and outcomes of this database will be spurious. RESULTS: We have outlined the
      data management practices for epidemiological studies that we have modeled for
      our research sites in seven Asian countries and one African country. CONCLUSION:
      Information from this model data management structure may help others construct
      reliable databases for large-scale epidemiological studies in less developed
      countries.

PMID- 16584572
TI  - Classification of protein quaternary structure by functional domain composition.
AB  - BACKGROUND: The number and the arrangement of subunits that form a protein are
      referred to as quaternary structure. Quaternary structure is an important protein
      attribute that is closely related to its function. Proteins with quaternary
      structure are called oligomeric proteins. Oligomeric proteins are involved in
      various biological processes, such as metabolism, signal transduction, and
      chromosome replication. Thus, it is highly desirable to develop some
      computational methods to automatically classify the quaternary structure of
      proteins from their sequences. RESULTS: To explore this problem, we adopted an
      approach based on the functional domain composition of proteins. Every protein
      was represented by a vector calculated from the domains in the PFAM database. The
      nearest neighbor algorithm (NNA) was used for classifying the quaternary
      structure of proteins from this information. The jackknife cross-validation test
      was performed on the non-redundant protein dataset in which the sequence identity
      was less than 25%. The overall success rate obtained is 75.17%. Additionally, to
      demonstrate the effectiveness of this method, we predicted the proteins in an
      independent dataset and achieved an overall success rate of 84.11% CONCLUSION:
      Compared with the amino acid composition method and Blast, the results indicate
      that the domain composition approach may be a more effective and promising high
      throughput method in dealing with this complicated problem in bioinformatics.

PMID- 16584573
TI  - Rapid Urban Malaria Appraisal (RUMA) III: epidemiology of urban malaria in the
      municipality of Yopougon (Abidjan).
AB  - BACKGROUND: Currently, there is a significant lack of knowledge concerning urban
      malaria patterns in general and in Abidjan in particular. The prevalence of
      malaria, its distribution in the city and the fractions of fevers attributable to
      malaria in the health facilities have not been previously investigated. METHODS:
      A health facility-based survey and health care system evaluation was carried out
      in a peripheral municipality of Abidjan (Yopougon) during the rainy season of
      2002, applying a standardized Rapid Urban Malaria Appraisal (RUMA) methodology.
      RESULTS: According to national statistics, approximately 240,000 malaria cases
      (both clinical cases and laboratory confirmed cases) were reported by health
      facilities in the whole of Abidjan in 2001. They accounted for 40% of all
      consultations. In the health facilities of the Yopougon municipality, the malaria
      infection rates in fever cases for different age groups were 22.1% (under one
      year-olds), 42.8% (one to five years-olds), 42.0% (> five to 15 years-olds) and
      26.8% (over 15 years-olds), while those in the control group were 13.0%. 26.7%,
      21.8% and 14.6%, respectively. The fractions of malaria-attributable fever were
      0.12, 0.22, 0.27 and 0.13 in the same age groups. Parasitaemia was homogenously
      detected in different areas of Yopougon. Among all children, 10.1% used a
      mosquito net (treated or not) the night before the survey and this was protective
      (OR = 0.52, 95% CI 0.29-0.97). Travel to rural areas within the last three months
      was frequent (31% of all respondents) and associated with a malaria infection (OR
      = 1.75, 95% CI 1.25-2.45). CONCLUSION: Rapid urbanization has changed malaria
      epidemiology in Abidjan and endemicity was found to be moderate in Yopougon.
      Routine health statistics are not fully reliable to assess the burden of disease,
      and the low level of the fractions of malaria-attributable fevers indicated
      substantial over-treatment of malaria.

PMID- 16584575
TI  - Rapid Urban Malaria Appraisal (RUMA) II: epidemiology of urban malaria in Dar es
      Salaam (Tanzania).
AB  - BACKGROUND: The thinking behind malaria research and control strategies stems
      largely from experience gained in rural areas and needs to be adapted to the
      urban environment. METHODS: A rapid assessment of urban malaria was conducted in
      Dar es Salaam in June-August, 2003 using a standard Rapid Urban Malaria Appraisal
      (RUMA) methodology. This study was part of a multi-site study in sub-Saharan
      Africa supported by the Roll Back Malaria Partnership. RESULTS: Overall, around
      one million cases of malaria are reported every year by health facilities.
      However, school surveys in Dar es Salaam during a dry spell in 2003 showed that
      the prevalence of malaria parasites was low: 0.8%, 1.4%, 2.7% and 3.7% in the
      centre, intermediate, periphery and surrounding rural areas, respectively. Health
      facilities surveys showed that only 37/717 (5.2%) of presenting fever cases and
      22/781 (2.8%) of non-fever cases were positive by blood slide. As a result,
      malaria-attributable fractions for fever episodes were low in all age groups and
      there was an important over-reporting of malaria cases. Increased malarial
      infection rates were seen in persons who travelled to rural areas within the past
      three months. A remarkably high coverage of insecticide-treated nets and a
      corresponding reduction in malarial infection risk were found. CONCLUSION: The
      number of clinical malaria cases was much lower than routine reporting suggested.
      Improved malaria diagnosis and re-defined clinical guidelines are urgently
      required to avoid over-treatment with antimalarials.

PMID- 16584574
TI  - Thalidomide attenuates nitric oxide mediated angiogenesis by blocking migration
      of endothelial cells.
AB  - BACKGROUND: Thalidomide is an immunomodulatory agent, which arrests angiogenesis.
      The mechanism of anti-angiogenic activity of thalidomide is not fully understood.
      As nitric oxide is involved in angiogenesis, we speculate a cross-talk between
      thalidomide and nitric oxide signaling pathway to define angiogenesis. The aim of
      present study is to understand the mechanistic aspects of thalidomide-mediated
      attenuation of angiogenesis induced by nitric oxide at the cellular level.
      METHODS: To study the cellular mechanism of thalidomide-mediated blocking of
      angiogenesis triggered by nitric oxide, we used two endothelial cell based
      models: 1) wound healing and 2) tube formation using ECV 304, an endothelial cell
      line. These cell-based models reflect pro-angiogenic events in vivo. We also
      studied the effects of thalidomide on nitric oxide mediated egg yolk
      angiogenesis. Thalidomide could block the formation of blood vessels both in
      absence and presence of nitric oxide. Thalidomide effects on migration of, and
      actin polymerization in, ECV 304 cells were studied at the single cell level
      using live cell imaging techniques and probes to detect nitric oxide. RESULTS:
      Results demonstrate that thalidomide blocks nitric oxide-mediated angiogenesis in
      egg yolk model and also reduces the number of tubes formed in endothelial cell
      monolayers. We also observed that thalidomide arrests wound healing in presence
      and absence of nitric oxide in a dose-dependent fashion. Additionally,
      thalidomide promotes actin polymerization and antagonizes the formation of
      membrane extensions triggered by nitric oxide in endothelial cells. Experiments
      targeting single tube structure with thalidomide, followed by nitric oxide
      treatment, show that the tube structures are insensitive to thalidomide and
      nitric oxide. These observations suggest that thalidomide interferes with nitric
      oxide-induced migration of endothelial cells at the initial phase of angiogenesis
      before cells co-ordinate themselves to form organized tubes in endothelial cells
      and thereby inhibits angiogenesis. CONCLUSION: Thalidomide exerts inhibitory
      effects on nitric oxide-mediated angiogenesis by altering sub-cellular actin
      polymerization pattern, which leads to inhibition of endothelial cell migration.

PMID- 16584576
TI  - Cutaneous hypersensitivity reactions to freshwater cyanobacteria--human volunteer
      studies.
AB  - BACKGROUND: Pruritic skin rashes associated with exposure to freshwater
      cyanobacteria are infrequently reported in the medical and scientific literature,
      mostly as anecdotal and case reports. Diagnostic dermatological investigations in
      humans are also infrequently described. We sought to conduct a pilot volunteer
      study to explore the potential for cyanobacteria to elicit hypersensitivity
      reactions. METHODS: A consecutive series of adult patients presenting for
      diagnostic skin patch testing at a hospital outpatient clinic were invited to
      participate. A convenience sample of volunteers matched for age and sex was also
      enrolled. Patches containing aqueous suspensions of various cyanobacteria at
      three concentrations were applied for 48 hours; dermatological assessment was
      made 48 hours and 96 hours after application. RESULTS: 20 outpatients and 19
      reference subjects were recruited into the study. A single outpatient produced
      unequivocal reactions to several cyanobacteria suspensions; this subject was also
      the only one of the outpatient group with a diagnosis of atopic dermatitis. No
      subjects in the reference group developed clinically detectable skin reactions to
      cyanobacteria. CONCLUSION: This preliminary clinical study demonstrates that
      hypersensitivity reactions to cyanobacteria appear to be infrequent in both the
      general and dermatological outpatient populations. As cyanobacteria are widely
      distributed in aquatic environments, a better appreciation of risk factors,
      particularly with respect to allergic predisposition, may help to refine health
      advice given to people engaging in recreational activities where nuisance
      cyanobacteria are a problem.

PMID- 16584577
TI  - Incidence rates and management of urinary tract infections among children in
      Dutch general practice: results from a nation-wide registration study.
AB  - BACKGROUND: We aimed to investigate incidence rates of urinary tract infections
      in Dutch general practice and their association with gender, season and
      urbanisation level, and to analyse prescription and referral in case of urinary
      tract infections. METHOD: During one calendar year, 195 general practitioners in
      104 practices in the Netherlands registered all their patient contacts. This
      study was performed by the Netherlands Institute for Health Services Research
      (NIVEL) in 2001. Of 82,053 children aged 0 to 18 years, the following variables
      were collected: number of episodes per patient, number of contacts per episode,
      month of the year in which the diagnosis of urinary tract infection was made,
      age, gender, urbanisation level, drug prescription and referral. RESULTS: The
      overall incidence rate was 19 episodes per 1000 person years. The incidence rate
      in girls was 8 times as high as in boys. The incidence rate in smaller cities and
      rural areas was 2 times as high as in the three largest cities. Throughout the
      year, incidence rates varied with a decrease in summertime for children at the
      age of 0 to 12 years. Of the prescriptions, 66% were in accordance with current
      guidelines, but only 18% of the children who had an indication were actually
      referred. CONCLUSION: This study shows that incidence rates of urinary tract
      infections are not only related to gender and season, but also to urbanisation.
      General practitioners in the Netherlands frequently do not follow the clinical
      guidelines for urinary tract infections, especially with respect to referral.

PMID- 16584578
TI  - Specific age-related signatures in Drosophila body parts transcriptome.
AB  - BACKGROUND: During the last two decades progress in the genetics of aging in
      invertebrate models such as C. elegans and D. melanogaster has clearly
      demonstrated the existence of regulatory pathways that control the rate of aging
      in these organisms, such as the insulin-like pathway, the Jun kinase pathway and
      the Sir2 deacetylase pathway. Moreover, it was rapidly shown that some of these
      pathways are conserved from yeast to humans. In parallel to genetic studies,
      genomic expression approaches have given us significant information on the gene
      expression modifications that occur during aging either in wild type or long
      lived mutant animals. But most of the genomic studies of invertebrate models have
      been performed so far on whole animals, while several recent studies in mammals
      have shown that the effects of aging are tissue specific. RESULTS: We used
      oligonucleotide microarrays to address the specificities of transcriptional
      responses in aging Drosophila in head, thorax or whole body. These fly parts are
      enriched in transcripts that represent different and complementary sets of genes.
      We present evidence for both specific and common transcriptional responses during
      the aging process in these tissues. About half of the genes described as
      downregulated with age are linked to reproduction and enriched in gonads. Greater
      downregulation of mitochondrial genes, activation of the JNK pathway and
      upregulation of proteasome subunits in the thorax of aged flies all suggest that
      muscle may be particularly sensitive to aging. Simultaneous age-related
      impairment of synaptic transmission gene expression is observed in fly heads. In
      addition, a detailed comparison with other microarray data indicates that in aged
      flies there are significant deviations from the canonical responses to oxidative
      stress and immune stress. CONCLUSION: Our data demonstrates the advantages and
      value of regionalized and comparative analysis of gene expression in aging
      animals. Adding to the age-regulated genes already identified in whole animal
      studies, it provides lists of new regionalized genes to be studied for their
      functional role in the aging process. This work also emphasizes the need for such
      experiments to reveal in greater detail the consequences of the transcriptional
      modifications induced by aging regulatory pathways.

PMID- 16584580
TI  - [Expression of SDF-1alpha and its receptor CXCR4 in acute leukemias and their
      relationship with extramedullary infiltration].
AB  - The study was aimed to explore the expression of stromal cell derived factor
      1alpha (SDF-1alpha) and its receptor CXCR4, and their relationship with the
      extramedullary infiltration in acute lymphoblastic, grannulocytic and monocytic
      leukemia. 66 cases of acute leukemia included 31 cases of acute lymphoblatic
      leukemia (ALL), 20 cases of acute grannulocytic leukemia (M(2)) and 15 cases of
      acute monocytic leukemia (M(4)+M(5)). There were 41 cases with extramedullary
      infiltration and 25 cases without-extramedullary infiltration. Enzyme-linked
      immunoabsorbent assay (ELISA) and flow cytometry were used to determine
      expression of SDF-1alpha and CXCR4 respectively on leukemia cells in peripheral
      blood and bone marrow of different groups. The results showed that average plasma
      level of SDF-1alpha in the ALL, M(4)+M(5), M(2) patients and the normal control
      were 1317.87 +/- 220.76, 1339.79 +/- 187.06, 1063.70 +/- 190.74, 1908.34 +/-
      135.55 (pg/ml) respectively. The average levels in the ALL, M(4)+M(5) and M(2)
      patients groups were lower than those in normal control group. Both levels in ALL
      and M(4)+M(5) patient groups were higher than that in M(2) patient group. The
      average levels of SDF-1alpha in patient group with extramedullary infiltration
      and patient groups without-extramedullary infiltration were 1252.49 +/- 263.12,
      1234.91 +/- 185.50 (pg/ml) respectively. The former seemed as if higher than the
      latter, but without statistical significance. The MFI of CXCR4 expression in ALL,
      M(4)+M(5), M(2) patient group were 78.47 +/- 33.96, 67.21 +/- 24.29, 41.66 +/-
      17.18, respectively. CXCR4 expression in ALL and M(4)+M(5) patient groups were
      higher than that in M(2) patient group (P > 0.05). There was no significant
      difference between the ALL and M(4)+M(5) patient group (P > 0.05). The MFI of
      CXCR4 expression in patients with extramedullary infiltration and patients
      without extramedullary infiltration were 81.72 +/- 27.63, 36.94 +/- 11.86
      respectively. The former was higher than the latter (P < 0.05). It is concluded
      that the higher expression of CXCR4 on acute lymphoblatic and monocytic leukemia
      cells may be one of the molecular mechanisms of extramedullary infiltration in
      both kinds of leukemia. The average plasma levels of SDF-1alpha decreased in
      leukemia patients and this decrease not related to the extramedullar
      infiltration, which may be due to the SDF-1alpha local expression in the organ
      infiltrated.

PMID- 16584579
TI  - A set of highly informative rat simple sequence length polymorphism (SSLP)
      markers and genetically defined rat strains.
AB  - BACKGROUND: The National Bio Resource Project for the Rat in Japan (NBRP-Rat) is
      focusing on collecting, preserving and distributing various rat strains,
      including spontaneous mutant, transgenic, congenic, and recombinant inbred (RI)
      strains. To evaluate their value as models of human diseases, we are
      characterizing them using 109 phenotypic parameters, such as clinical
      measurements, internal anatomy, metabolic parameters, and behavioral tests, as
      part of the Rat Phenome Project. Here, we report on a set of 357 simple sequence
      length polymorphism (SSLP) markers and 122 rat strains, which were genotyped by
      the marker set. RESULTS: The SSLP markers were selected according to their
      distribution patterns throughout the whole rat genome with an average spacing of
      7.59 Mb. The average number of informative markers between all possible pairs of
      strains was 259 (72.5% of 357 markers), showing their high degree of
      polymorphism. From the genetic profile of these rat inbred strains, we
      constructed a rat family tree to clarify their genetic background. CONCLUSION:
      These highly informative SSLP markers as well as genetically and phenotypically
      defined rat strains are useful for designing experiments for quantitative trait
      loci (QTL) analysis and to choose strategies for developing new genetic
      resources. The data and resources are freely available at the NBRP-Rat web site
      1.

PMID- 16584581
TI  - [Expression of the transcription factor PAX5 in childhood acute leukemic cells].
AB  - To investigate transcription factor PAX5 expression characteristics in childhood
      acute leukemic cells, expression levels of PAX5 and CD19 mRNA in 6 hematological
      tumor cell lines and bone marrow cells of 6 normal children, 58 de novo patients
      and 4 relapse acute leukemic children, including 39 cases of B-ALL, 10 cases of T
      ALL and 13 cases of AML, were detected by a real-time RT-PCR. The results showed
      that PAX5 and CD19 mRNA expression levels were 2.35% and 2.52% in Namalwa (B-cell
      lines) respectively, but almost not detectable in other T- and myeloid cell
      lines. Among clinical samples, expression of PAX5 mRNA in B-ALL was significantly
      higher than that in T-ALL and AML (P = 0.029 and P = 0.013 respectively). PAX5
      expression was significantly lower in T-ALL and AML than that in normal controls.
      The difference of PAX5 mRNA expression levels between T-ALL and AML was not
      significant. Individual difference of PAX5 mRNA expression levels in children
      with B-ALL was great. Moreover, PAX5 mRNA expressions in de novo and relapse
      patients with B-ALL were significantly higher than those in remission (P = 0.011
      and P = 0.006 respectively). As binding sites for B-cell specific activator
      protein have been identified in the promoter regions of CD19, the study found
      that in B-ALL, there was clear correlation between the expression levels of PAX5
      and CD19, which was also studied by real-time RT-PCR. It is concluded that PAX5
      transcripts are readily detectable and quantifiable in clinical materials with B
      ALL by real-time RT-PCR. The strong PAX5 mRNA expression in some B-ALL can be
      considered to be particularly interesting for further analysis.

PMID- 16584583
TI  - [Relationship between VEGF and MMP-2, MMP-9 in 82 patients with acute myeloid
      leukemia].
AB  - In order to investigate the relationship between VEGF and matrix
      metalloproteinase (MMP)-2, -9 in acute myeloid leukemia patients, and evaluate
      the significance of them in extramedullary leukemic invasion, the expressions of
      MMP-2 mRNA, MMP-9 mRNA, VEGF mRNA in bone marrow from 86 patients with acute
      myeloid leukemia (AML), as well as human hematopoietic cell lines were analyzed
      by reverse transcription-polymerase chain reaction (RT-PCR). The proteolytic
      activities of MMP-2 and MMP-9 in the supernatants were measured by zymography.
      The VEGF protein in serum of all samples was detected by ELISA. All these results
      were analyzed for determination of the relationship between VEGF and MMP-2, MMP
      9. The results showed that there was a positive correlation between expressions
      of MMP-2 mRNA or MMP-9 mRNA and VEGF mRNA or protein. But no such correlation was
      demonstrated in the AML (CR) and normal control (NC) groups. A higher expression
      level of MMP-2 and MMP-9 in the VEGF positive group was found, as compared with
      the negative group (P < 0.05). More extramedullary infiltration occurred in VEGF
      positive groups than that in VEGF negative groups of AML. The expression of bcl-2
      in HL-60 cells was upregulated by VEGF. It is concluded that there are
      significantly positive correlations between the expression of MMP-2 and MMP-9
      with VEGF mRNA or protein levels in AML patients. VEGF can upregulate the
      expression of MMP-2, MMP-9 in HL-60 and a part of the primary leukemic cells.
      VEGF and MMP-2, MMP-9 may participate in the extramedullary leukemic invasion of
      AML patients.

PMID- 16584582
TI  - [Rac1 expression and its effects on the cell cycle progression and apoptosis in
      human acute leukemic cell line HL-60].
AB  - The study was aimed to investigate the expression of Rac1 in human acute leukemic
      cell line HL-60 and effect of Rac1 on cell cycle progression and apoptosis. The
      mRNA expression of Rac1 in HL-60 cell line and normal human peripheral blood
      mononuclear cells (PBMNC) were examined by semi-quantitative RT-PCR. After
      transfection of HL-60 cells with different concentrations of Rac1 antisense
      oligodeoxynucleotide (ASODN) by means of FuGENE6, the survival, cell cycle,
      apoptosis of HL-60 cells were observed through MTT assay, FCM test, Wright
      Giemsa, acridine orange/ethidium bromide (AO/EB) and Annexin V-FITC/PI staining
      test respectively. The results showed that Rac1 relative amount in HL-60 was 0.84
      +/- 0.13, while it in the normal PBMNC was 0.26 +/- 0.1 (P < 0.01); the
      expression of Rac1 in HL-60 cells was significantly upregulated. Compared with
      sense oligodeoxynucleotide (SODN), HL-60 cell viability, after exposure to ASODN
      at a concentration of 2.0 g/L decreased, (73.7 +/- 5.0)% vs (93.2 +/- 3.0)% (P <
      0.01), while the proportion of G(1) cells increased as (52.1 +/- 6.8)% vs (31.6
      +/- 4.7)% (P < 0.05), the percentage of Annexin V positive cells increased, (19.2
      +/- 2.1)% vs (4.1 +/- 1.7)% (P < 0.01), and HL-60 cells were observed to have
      formation of apoptotic bodies. The data presented indicate that Rac1 may be
      involved in regulation of HL-60 cell cycle and apoptosis, promote
      overproliferation of HL-60 cells and inhibit their apoptosis.

PMID- 16584584
TI  - [Inhibition of proliferation and induction of apoptosis and differentiation of
      leukemic cell line HL-60 by sodium valproate].
AB  - To investigate the influence of sodium valproate (VPA) on proliferation,
      apoptosis and differentiation of HL-60 cell line, effect of VPA in various
      concentrations on proliferation of HL-60 cells was detected by MMT; Wright-Giemsa
      staining was performed to observe the morphologic changes of HL-60 cells; NBT
      experiment was used to test the differentiation of HL-60 cells; flow cytometry
      was used to observe cell cycles and analyze the apoptosis. The results indicated
      that the changes of the growth curve showed inhibition of proliferation of HL-60
      cells. After a 24-48 hours culture with 2 mmol/L VPA, the cells exhibited nuclear
      shrinkage, pyknosis fragmentation and appearance of apoptosis bodies. The
      percentage of the annexin V(+)/PI(-) cells which were apoptotic increased from
      2.9% to 17.1%; hypodiploid peak was observed; the percentage of HL-60 cells in
      G(1) phase increased from 51.1% to 84.6% and the cells in S phase decreased from
      37.9% to 14.4%. After a week culture with 0.25 mmol/L VPA, the cells exhibited
      characteristics of differentiation. The percentage of NBT positive cells was (47
      +/- 2)%. It is concluded that VPA can inhibit the proliferation of HL-60 cells
      while inducing differentiation and apoptosis of these cells. The mechanism needs
      to be further studied.

PMID- 16584585
TI  - [Thapsigargin-induced apoptosis of K562 cells and its mechanism].
AB  - The aim was to study the apoptotic induction effect of thapsigargin on leukemia
      cell line K562 and its possible mechanism. After the treatment of leukemia cell
      line K562 by thapsigargin, morphological change of apoptotic cells was
      investigated by AO/EB fluorescent staining under fluorescent microscope;
      apoptosis rate was determined with annexin V-FITC/PI double staining by flow
      cytometry; intracellular calcium concentrations ([Ca(2+)]i) were measured by
      fluorescence spectrophotometer with calcium sensitive fluorescence indicator Fura
      2/AM; mitochondrial transmembrance potentials (Delta Psi m) was detected on flow
      cytometry through staining of Rhodamine (Rh123); the changes of caspase-3, -7, 
      9, -12, cytochrome C, GRP78 proteins were detected by Western blot. The results
      showed that K562 cells cultured in 4 micromol/L thapsigargin for 48 hours
      exhibited typical morphological changes of apoptotic cells under fluorescent
      microscope, including shrinkage of cell, condensation of chromatin, breakage of
      nuclear, formation of apoptotic bodies, fluorescence of yellow green and pellet
      observed in early apoptoyic cells and hyacinth fluorescence of chromatin showed
      in late apoptotic cells. 24 and 48 hours after exposure to 1, 2, 4, 8 micromol/L
      thapsigargin, the apoptotic rates of K562 were respectively 7.51%, 11.65%,
      23.22%, 30.56% and 12.85%, 20.27%, 31.51%, 44.16%, in dose-dependent manner, and
      were statistically significant when compared with the controls (P < 0.05). The
      apoptotic rate of K562 was dose- and time-dependent in experiment range. The
      enhancement of [Ca(2+)]i and the decrease of the Delta Psi m in K562 cells were
      induced by thapsigargin and were dose-dependent in experiment range, compared
      with control, P < 0.05. Western blot results indicated that cleavage and
      activation of caspase-3, -7, -9, -12, releasing of cytochrome C from
      mitochondria, upregulation of GRP78 expression at the endoplasmic reticulum were
      induced in K562 cells after 24 hours exposure of 4 micromol/L thapsigargin. It is
      concluded that thapsigargin induces endoplasmic reticulum stress-induced
      apoptosis in K562 cells. Endoplasmic reticulum is a novel important initiatory
      site of apoptosis in cells; the cleavage and activation of caspase-3, -7, -9, -12
      play very important role in endoplasmic reticulum stress-induced apoptosis of
      K562 cells and is one of the important mechanisms for thapsigargin-induced
      apoptosis. Thapsigargin-induced apoptosis in K562 cells is associated closely
      with the disruption of the Delta Psi m and the release of cytochrome C from
      mitochondria, mitochondria participates in endoplasmic reticulum stress-induced
      apoptosis in K562 cells.

PMID- 16584586
TI  - [Analysis of expression of mitosis checkpoint gene chfr in bone marrow cells of
      acute leukemia patients].
AB  - This study was purposed to investigate the significance of mitosis checkpoint
      gene chfr expression in acute leukemia (AL). 2 ml of bone marrow were extracted
      from each of 46 AL patients and 10 normal donors as control and their mononuclear
      cells were isolated. Then, their chfr expression was detected by using RT-PCR and
      immunohistochemistry. Normal control blood samples were also analyzed. The
      results showed that in 15 out of 28 cases of acute non-lymphocytic leukemia and
      13 out of 18 cases of acute lymphocytic leukemia expression of chfr gene mRNA and
      protein significantly decreased as compared with control. The cytogenetic
      analysis of patients with a decreased Chfr expression revealed abnormal
      chromosome. In conclusion, Chfr gene is a leukemia-related gene and may play an
      important role in leukemia pathogenesis.

PMID- 16584587
TI  - [Immunophenotypic features in leukemia of NK cell series].
AB  - The aim was to investigate the immunophenotypes of NK series leukemia.
      Immunophenotypes of 297 cases of acute leukemia (AL) were measured by flow
      cytometry, and these immucopenotypic features were analyzed. The results showed
      that 43 out of 297 cases of AL (14.5%) were CD56 positive. 6 cases were NK series
      leukemia and 37 cases were acute myelogenous leukemia with CD56 expressed. One
      patient has been diagnosed as myeloid/NK cell precursor acute leukemia, two
      patients were blastic NK cell leukemia, one was supposed to be NK-like T-cell
      lymphoma/leukemia, while another one was large granular lymphocyte leukemia
      (LGLL). It is concluded that almost all of CD56 positive leukemia were acute
      myelogenous leukemia with CD56 expressed. The immunophenotypes of NK series
      leukemia were antigens from hematopoietic stem cells to T/NK progenitor cells
      with meyloid antigen positive, and through NK progenitors to mature NK cells. The
      immunophenotypes of heterogeneous NK leukemia cells are different, that should be
      carefully distinguished.

PMID- 16584588
TI  - [Immunologic classification used in typing of 68 cases of acute leukemias].
AB  - To evaluate the significance of immunologic classification for typing of acute
      leukemia (AL). 68 cases of AL were classified by morphologic and immunologic
      typings. The results showed that the consistency rate was 94.1% between
      morphology and immunology, and 4 morphologic misdiagnosed cases were corrected by
      immunology; CD13 and CD33 were special myeloid lineage-associated antigens; AML
      M(3) was often CD34 low-expressed and HLA-DR-negative; CD14 was often expressed
      in AML-M(4) and M(5); lymphoid lineage-associated antigens (CD7) were easily
      found in ANLL, and myeloid lineage-associated antigens were also found in ALL. In
      conclusion, immunologic classification can improve the accuracy in acute leukemia
      diagnosis. The diagnosis of some special AL, such as acute unidentified leukemia
      (AUL), AML-M(0) and so on, must rely on immunologic classification.

PMID- 16584589
TI  - [Detection of the complex chromosomal aberrations in acute lymphoblastic leukemia
      by means of multiplex fluorescence in situ hybridization].
AB  - This study was aimed to establish the technique of multiplex fluorescence in situ
      hybridization (M-FISH) and to explore its usefulness in detection of complex
      chromosomal aberrations (CCAs) in acute lymphoblastic leukemia (ALL). Five ALL
      patients with CCAs were analyzed by combining the techniques of conventional
      cytogenetics (CC) and M-FISH. The results demonstrated that M-FISH confirmed the
      aberrations previously detected by CC, such as t (9;22), t (1;19) and t (y;1),
      and revealed new abnormalities as der (1) (1::3::7), der (6) t (6;9) (q?;p13),
      der (1) t (1;11), der (12) t (1;12), der (3) t (3;5), der (2) t (2;16), der (9)
      (9::18::7) and der (7) (9::18::7), and also corrected the wrong results in CC.
      Among these abnormalities, der (9) (9::18::7) and der (7) (9::18::7) were
      reported for the first time. In conclusion, M-FISH has proved to be useful in
      characterization of the CCAs in ALL, and it is an essential method to refine the
      karyotype analysis.

PMID- 16584590
TI  - Detection of complex karyotype in a myelodysplastic syndrome cell line (MUTZ-1)
      by metaphase fluorescence in situ hybridization.
AB  - This study was aimed to investigate the cytogenetic changes of MDS cell line
      (MUTZ-1) with chromosome 5q deletion. R-banding analysis was used to identify
      chromosome aberrations in MDS cell line and Vysis Spectra Vysion M-FISH was used
      to further characterize chromosomal complex karyotype. The results indicated that
      M-FISH exhibited obvious chromosomal aberrations with high frequency including
      translocation, insertion, breakage and rearrangement, deletion and increasement
      of chromosome number, the complex karyotype of MUTZ-1 was shown as 50, xx, der
      (1) t (1;2), ins (1;14), +der (2) t(2;19), der (3) t (3;5), der (3) (3::5::22),
      5q-, der (6) t (3;6), der (7) (18::7::17), +8, +der (9) t (1;9), der (10) t
      (1;10), +11, +12, der (?13) (10::13::5::8), der (14) t (8;14), der (14) t (14,
      15), der (15) t (15;21) x 2, +17, +18, -21, -22. It is concluded that M-FISH
      analysis revealed obvious changes in complex karyotype of MDS cell line MUTZ-1,
      and the M-FISH technique can increase accuracy of detection for chromosomal
      complex karyotype, and help diagnosis and prognostic evaluation of MDS.

PMID- 16584591
TI  - [Four-color flow cytometric immunophenotypic features of blasts in
      myelodysplastic syndromes].
AB  - This study was aimed at exploring the immunophenotypic features of blasts in
      patients with myelodysplastic syndromes (MDS). Four-color flow cytometry using
      conventional and secondary gating strategies was used to immunophenotype blasts
      and the CD34 positive cells in bone marrow nucleated cells of 29 patients with
      MDS. The results showed: (1) with progression of MDS from RA/RAS, RAEB to RAEB-T,
      the proportion of CD34(+) cells were gradually increased from 8.0%, 46.4% to
      76.8% (P < 0.05); (2) using CD45 vs SSC gating strategy, with the transformation
      of RA/RAS, RAEB to RAEB-T, the expression of HLA-DR, CD13, CD33, CD117 were also
      gradually increased (P < 0.05), and the expression of CD15 was gradually
      decreased (P < 0.05); (3) using CD45 vs CD34 gating strategy, the expression of
      HLA-DR, CD13, CD33, CD117 on blasts were higher by secondary gating method than
      those by conventional gating (P < 0.05). However, there were no significant
      difference (P > 0.05) in the expression of above-mentioned antigens on CD34(+)
      cells among different MDS subtypes. It is concluded that conventional gating
      method can reflect MDS progression from RA/RAS, RAEB to RAEB-T, and secondary
      gating strategy may accurately reflect the biological features of blasts in MDS.
      Abnormal expression of CD34 is related to the immaturity level and heterogeneity
      of blast cells, which is beneficial to the diagnosis of clinically suspected MDS
      incapable of diagnosing with morphology and cytogenetics.

PMID- 16584592
TI  - Genetically modified myeloma cell vaccine inducing antitumor immune response in
      vivo.
AB  - This study was aimed to evaluate the in vivo antitumor effect of genetically
      modified myeloma cell vaccine on human myeloma xenografts implanted into nonobese
      diabetic/severe combined immunodeficiency (NOD/SCID) mice. Human immune system
      was established in NOD/SCID mice by intraperitoneal injection of human peripheral
      blood lymphocytes (PBLs). After being inoculated subcutaneously with irradiated
      myeloma cell line sko-007, adenovirally transferred with GFP or p53, granulocyte
      macrophage colony-stimulating factor (GM-CSF) and B7-1 genes, huPBL-NOD/SCID mice
      were challenged by subcutaneous injection of non-transferred sko-007 cells. The
      results indicated that Ad-p53/GM-CSF/B7-1-infected sko-007 cell vaccination
      significantly reduced local tumor growth compared with controls.
      Histopathological and immunohistochemical analysis showed that tumor tissues
      increasingly displayed diffuse necrosis, mainly caused by apoptosis, accompanied
      with significant fibroplasias and blood vessel hyperplasia, and human T cells
      infiltrated into the tumor tissues. It is concluded that transgenic p53, GM-CSF
      and B7-1 expression produces an immune response against myeloma cells and may be
      of therapeutic value for multiple myeloma in human being.

PMID- 16584594
TI  - Preliminary investigation of 2-methoxyestradiol inducing differentiation of
      myeloma cell line CZ-1.
AB  - This study was aimed to investigate whether 2-methoxyestradiol (2ME2) could exert
      effect of inducing differentiation on myeloma cells. A myeloma cell line CZ-1
      secreting lambda light chain protein was used as an object of study. The CZ-1
      cell morphology was observed by Wright's staining, the CD49e expression on cell
      surface after treatment with 2ME2 was detected by flow cytometry, the
      concentration of lambda light chain protein in the supernatant was assayed by
      immuno-scattering turbidity method. The results showed that treatments with 0.1
      0.5 micromol/L 2ME2 for 72 hours resulted in some mature morphological changes of
      CZ-1 cells, such as the ratio of karyoplasms going down, nucleolus reducing or
      disappearing, chromatin getting rougher and more compacted; the CD49e positive CZ
      1 cells increased by 2ME2 with concentrations of 0.1 micromol/L to 0.5 micromol/L
      in a concentration-dependent manner. The statistical difference from the control
      group was significant; the concentration of lambda light chain protein increased
      from control group 29.3 +/- 2.77 microg/ml to 35.97 +/- 2.6 microg/ml (P < 0.05)
      after exposure to 0.1 micromol/L 2ME2 for 72 hours, and the treatment of 0.5
      micromol/L 2ME2 up-regulated lambda light chain protein to 79.67 +/- 1.88
      microg/ml (P < 0.01) continuously. It is concluded that 2ME2 at low-concentration
      can induce differentiation of the CZ-1 cells to mature, which provides a new, and
      safe strategy for myeloma therapy.

PMID- 16584593
TI  - [Effects of proteasome inhibitor PS-341 on the multiple cytokine expressions of
      mesenchymal stem cells from bone marrow in patients with multiple myeloma].
AB  - To explore the effects of proteasome inhibitor PS-341 on the cytokine expressions
      of mesenchymal stem cells (MSC) in patients with multiple myeloma (MM), MSCs of
      11 patients were cultured in medium of RPMI 1640 containing 10% FBS. When cells
      grew to 5 x 10(5) - 1 x 10(6), cells were exposed to 50 nmol/L PS-341 for 4
      hours, then harvested. The expressions of IL-6, IL-1beta and SCF were detected by
      RT-PCR. The results indicated that after treatment with PS-341 the expressions of
      IL-6, IL-1beta and SCF of MSCs decreased markedly, especially that of IL-1beta,
      compared with control (P < 0.05, P < 0.01, P < 0.05, respectively). There were
      obviously differences of IL-1beta expression between refractory/relapsed group
      and complete remission (CR) group and IL-1beta expression was inhibited more
      seriously in CR group, whereas there were no significant differences of IL-6 and
      SCF expression between two groups; IL-1beta expression of patients treated with
      PS-341 was not detected; there were not effects of IL-1beta expression on
      expressions of IL-6 and SCF. It is concluded that proteasome inhibitor PS-341
      downregulated the expressions of IL-6, IL-1beta and SCF of MSCs in patients with
      MM.

PMID- 16584595
TI  - [Inhibitory effect of curcumin on angiogenesis induced by brain derived
      neurotrophic factor from multiple myeloma cells].
AB  - In order to explore the probability of curcumin treating multiple myeloma (MM)
      via the inhibition of angiogenesis, the expressions of brain derived neurotrophic
      factor (BDNF) and its specific receptor in human MM cells and endothelial cells
      were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The
      angiogenic activity was evaluated by endothelial cell migration assay and tubule
      formation assay in vitro. The results showed that exogenous BDNF significantly
      induced endothelial cell tubule formation and endothelial cell migration, these
      two effects were inhibited by curcumin. Furthermore, BDNF was detected in the MM
      cell and TrkB was detected in the endothelial cell and curcumin depressed the
      mRNA expression of BDNF and TrkB in the dose- and time-dependent manners. It is
      concluded that BDNF is a novel angiogenesis protein. Curcumin interrupts the
      interaction between multiple myeloma cells and endothelial cells by reducing TrkB
      expression in endothelial cells and inhibiting BDNF production in multiple
      myeloma cells, eventually, resulting in inhibition of angiogenesis. This is
      probably one part of the mechanism of the curcumin treating MM via the inhibition
      of angiogenesis.

PMID- 16584596
TI  - [Nude mice intraperitoneally transfused with ex vivo expanded bone marrow CD34+
      CD59+ cells from patients with paroxysmal nocturnal hemoglobinuria].
AB  - Ex vivo expanded human bone marrow CD34(+)CD59(+) cells from patients with
      paroxysmal nocturnal hemoglobinuria (PNH) were transplanted into BALB/c mice in
      order to investigate their proliferation ability and reconstruction of
      hemopoiesis, and to lay the groundwork for clinical ABMT/APBSCT in PNH patients.
      CD34(+)CD59(+) cells were selected from the bone marrow mononuclear cells in PNH
      patients by using immunomagnetic positive double sorting. Sublethally irradiated
      BALB/c mice were transplanted with CD34(+)CD59(+) cells enriched from bone narrow
      of PNH patients. The results showed that human CD45(+) cells were detected in the
      bone marrow, spleen and peripheral blood of the nude mice by flow cytometry and
      DNA analysis at 6 weeks post-transplant. Blood routine indicators of nude mice
      were found to recover to some extent, but did not fully recover. It is concluded
      that ex vivo expanded bone marrow CD34(+)CD59(+) cells from patients with
      paroxysmal nocturnal hemoglobinuria could keep their biological characteristics
      and ability to reconstruct hemopoiesis in irradiated BALB/c mice.

PMID- 16584597
TI  - Bone marrow angiogenesis in aplastic anemia.
AB  - The objective of this study was to investigate the status of bone marrow
      angiogenesis in aplastic anemia (AA). Bone marrow specimens from 32 patients with
      AA and 16 normal controls were studied. The number of bone marrow microvessels
      was examined by means of immunohistochemical staining for CD34. Determination of
      microvessel density (MVD) and angiogenesis grading were done in a blinded manner.
      The results showed that the bone marrow MVD in patients with AA was significantly
      lower than that in healthy subjects (P < 0.01). MVD in patients with severe and
      moderate AA was lower than that in control group, respectively (P < 0. 01). There
      is significant MVD difference between severe AA and moderate AA (P < 0.05).
      Angiogenesis grade and MVD in AA were positively correlated (r = 0.64, P < 0.01).
      It is concluded that bone marrow angiogenesis in AA patients is lower than that
      in normal controls. Defect of angiogenesis in bone marrow may play a role
      resulting in or aggravating hematopoietic aplasia in patients with AA.

PMID- 16584598
TI  - [Effects of stromal cell-derived factor 1 and platelet factor 4 on the adhesion
      characteristics and chemotactic function of ex vivo expanded umbilical cord blood
      CD34+ cells].
AB  - To investigate the effects of stromal cell-derived factor 1 (SDF-1) and platelet
      factor 4 (PF4) on the homing-related function of expanded ex vivo umbilical cord
      blood CD34(+) cells, purified cord blood CD34(+) cells were cultured in serum
      free medium containing a HGF combination of FL + SCF + TPO (FST) with either 100
      ng/ml SDF-1 alone, 100 ng/ml PF4 alone, or both of these 2 cytokines. The
      expansion rate of CD34(+) cells, colony formation, homing-related functions
      including expression of homing-related adhesion molecules of expanded CD34(+)
      cell, adhesion activity and chemotactic function of the re-selected expanded
      CD34(+) cells were evaluated at different time points. The results showed that
      expansion rate of CD34(+) cells and expansion multiple of CFU in SDF-1 groups
      were higher than those in control. The expression of CD49e on the expanded
      CD34(+) cells was remarkable up-regulated, in contrast, expression of CXCR-4 on
      the expanded CD34(+) cells was remarkable down-regulated in SDF-1 groups. The
      expression of CD49e, CD54 and CXCR-4 on the expanded CD34(+) cells were
      remarkably up-regulated in the PF4 groups. In all the SDF-1 group, PF4 group and
      SDF-1 plus PF4 group, the ability of expanded CD34(+) cells adhering to
      fibronectin layer were higher than those in the control on day 10. Spontaneous
      migration rate of expanded CD34(+) cells in SDF-1 groups were higher than those
      in control, while SDF-1-induced migration rate were lower than those in control
      on day 10. SDF-1-induced migration rate in PF4 groups were higher than those in
      control on day 10. Spontaneous and SDF-1-induced migration rate of expanded
      CD34(+) cells in the SDF-1 plus PF4 groups were higher than those in control on
      day 10. It is concluded that, SDF-1 and PF4 can up-regulate expression of
      adhesion molecules on expanded CD34(+) cells, and retain the adherent and
      migration ability of expanded CD34(+) cells, which is helpful for the homing of
      expanded CD34(+) cells. In short, SDF-1 and PF4 are helpful for the homing
      related function of the expanded UCB HSPC.

PMID- 16584599
TI  - [Expression of HOXB4 in cord blood progenitor cells expanded in vitro].
AB  - HOXB4, a member of homeobox gene family, is closely related to the self-renewing
      and proliferative ability of primitive hematopoietic stem/progenitor cells
      (PHSC/PHPC). This study was aimed to investigate the self-renewing level of cord
      blood progenitor cells (CBPC) expanded in vitro. The HOXB4 expression at mRNA
      level was assayed by using real time RT-PCR. The results indicated that as
      culture prolonged, the total cells, CD34(+) cells greatly increased, however the
      HOXB4 expression gradually declined, even down to undetectable level similar to
      that of mature lymphocytes. Meanwhile, it was shown that CD34(+) cells co
      cultured with bone marrow mesenchymal stem cells (BM-MSC) could abate the decline
      of HOXB4 expression. It is concluded that the self-renewing potential of CD34(+)
      cells gradually decreased during expansion in vitro, co-culture with BM-MSC was
      helpful to CD34(+) cell expansion and slowed the loss trend of its self-renewal.

PMID- 16584600
TI  - [Supportive effects of human aorta-gonad-mesonephros-derived stromal cells on
      umbilical cord blood LTC-IC].
AB  - The objective of this study was to explore the supportive effects of human aorta
      gonad-mesonephros (AGM)-derived stromal cells on human umbilical cord blood long
      term culture-initiating cells (LTC-IC). A co-culture system was established with
      human AGM stromal cells and umbilical cord blood CD34(+) cells. Different stromal
      cells derived from human AGM region (hAGM S1-S5) were plated on 24-well plates as
      feeder cells. CD34(+) cells were positively selected from human umbilical cord
      blood through immunomagnetic bead selection method, seeded on the feeder cells,
      and co-cultured for 8 weeks. The hematopoietic cells were collected at 5, 6, 7
      and 8 weeks for CFC analysis. Frequencies of LTC-IC in umbilical cord blood
      CD34(+) cells after co-culture with AGM stromal cells were detected through
      limiting dilute analysis (LDA). The results showed that there was no any
      hematopoietic CFC in the feeder cell-free culture system after 5 weeks of co
      culture. However, in AGM feeder cells culture systems, there were still CFCs
      after 5 weeks of co-culture, which indicated that human AGM stromal cells could
      maintain LTC-IC in vitro. In groups of hAGM feeders, hAGMS3 and S4 had better
      supportive effects than other AGM groups (P < 0.05). The absolute number of LTC
      IC in hAGM S3 and S4 culture systems got expansion up to (176 +/- 46)% and (187
      +/- 52)% respectively without significant difference between hAGMS3 and S4 (P >
      0.05). It is concluded that human AGM stromal cells S1-S5 support the maintenance
      of umbilical blood LTC-IC in vitro, while hAGMS3 and S4 cells have better effects
      on maintaining LTC-IC and expansion of LTC-IC.

PMID- 16584601
TI  - [Preliminary study on human mature placenta tissue-derived hematopoietic
      stem/progenitor cells].
AB  - Clinical transplantation has indicated that cord blood (CB) can be used in the
      hematopoietic reconstitution in the children, but not well used in the adult
      patients because of the low cell amount. The present study aimed to explore the
      capability of proliferation and differentiation of the hematopoietic
      stem/progenitor cells derived from human mature placenta tissue (PT) in vitro,
      and to find a new source of hematopoietic/progenitor cells for clinical
      transplantation. CD34(+) cells in human mature placenta tissue were isolated and
      characterized by using enzyme-digestion method and flow cytometry. A long culture
      system without cytokines was established with human mature placenta tissue
      derived mononucleated cells and cord blood mononuclear cells. The number of
      nucleated cells was weekly counted in culture for 14 weeks. The number of CFC was
      counted in culture for 2 weeks. The results showed that the CFC yields (CFU-GM,
      186.90 +/- 24.52; BFU-E, 101.40 +/- 13.35) and the percentage of CD34(+) cells
      (2.74 +/- 0.61%) and CD34(+)/CD38(-) cells (2.46 +/- 0.42%) in placenta tissue
      (PT) were higher than CFC (CFU-GM, 136.90 +/- 25.15; BFU-E, 49.20 +/- 8.13),
      CD34(+) cells (1.73 +/- 0.32%) and CD34(+)/CD38(-) cells (0.80 +/- 0.25%) in cord
      blood (CB). The MNCs from PT have shown more survival ability than the cells from
      CB in the long-term cell culture condition; and the cells from PT increased by 2
      times. It is concluded that the placenta may be another hematopoietic organ in
      ontogeny. The cells from placenta were more juvenile, and may be favorable source
      for clinical stem cell transplantation.

PMID- 16584602
TI  - [Effects of sensitized donor lymphocyte infusion on the chimerism and graft
      versus-host disease after nonmyeloablative allogeneic stem cell transplantation].
AB  - To explore whether the complete donor chimerism could be achieved and graft
      versus-host disease could be alleviated by donor lymphocyte infusion which was
      sensitized by the skin of the recipient, female C57BL/6 mice (H-2(b), B6) as
      recipients received total body irradiation (TBI) of 5.5 Gy ((60)Co gamma-ray) on
      day 0 followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).
      The allo-grafts consisted of 2 x 10(7) peripheral hematopoietic stem cells from
      mobilized male BALB/c (H-2(d)) donor mice with the granulocyte colony-stimulating
      factor (G-CSF). Day 2 after allo-HSCT, the recipient mice were given 200 mg/kg
      cyclophosphamide intraperitoneally. Afterwards these recipient mice were infused
      2 x 10(6) sensitized or unsensitized-donor lymphocytes at the 28 days after
      transplantation. The results showed that the mice receiving sensitized-donor
      lymphocyte infusion did not suffer from GVHD and the phenotypic character of the
      recipient mice (black color) converted to that of the donor mice (white color),
      and to become full-donor chimerism. It was found that the ratio of CD4(+)/CD8(+)
      T lymphocytes of them decreased at the earlier period and increased after half
      month, but which were also lower than that of the normal value. While various
      grades of acute GVHD was observed in that of the control group and the mixed
      chimeras were maintained, though it increased a little, and the ratio of
      CD4(+)/CD8(+) T lymphocytes increased at first, then decreased to the normal
      level half month later. It is concluded that sensitized DLI converted mixed to
      complete donor chimerism without GVHD, and the rate of CD4(+)/CD8(+) has close
      relation to the incidence of GVHD.

PMID- 16584603
TI  - [Influence of G-CSF mobilization on functions of donor T lymphocyte subpopulation
      and acute graft-versus-host disease].
AB  - To investigate the influence of G-CSF mobilization on functions of donor T
      lymphocyte subpopulation and acute graft-versus-host disease, peripheral blood
      samples of 20 healthy donors were collected before and after G-CSF mobilization.
      The whole blood was diluted with IMDM in ratio of 1:1 and then incubated with PMA
      + ionomycin + monensin at 37 degrees C, 5% CO2 for 4 hours. After being mobilized
      and stained, the IL-4, IFN-gamma and IL-2 positive cells were counted with three
      color flow cytometry. The results showed that before G-CSF mobilization, the
      percentages of donor's CD3(+)IFN-gamma(+), CD4(+)IFN-gamma(+), CD8(+)IFN-gamma(+)
      T cells were 3.2% (0% - 45.9%), 1.3% (0% - 23.8%) and 1.5% (0% - 22.2%)
      respectively. The percentage of above mentioned cells in donor increased to 19.2%
      (0% - 53.9%), 9.5% (0% - 49.5%), 7.5% (0% - 38.1%) respectively after G-CSF
      mobilization. The IL-2 positive CD3(+), CD4(+) and CD8(+) T cell percentage in
      pre-G-CSF mobilized donors was 1.5% (0% - 31%), 0.8% (0% - 30.0%) and 0% (0% -
      5.3%) respectively and subsequently increased to 25.7% (0% - 51%), 19.8% (0% -
      39.7%), 4.6% (0% - 20.9%) respectively after G-CSF mobilization. The IL-4
      positive T subpopulation did not increased significantly after G-CSF
      mobilization. In the early stage after peripheral blood stem cell
      transplantation, donor's Tc1 percentage in aGVHD group was significantly higher
      than that in non-aGVHD group. The morbidity of severe aGVHD in high Tc2
      percentage group was significantly lower than that in low Tc2 percentage group.
      It is concluded that the donor's type I T cells increase after G-CSF
      mobilization, the Tc1 percentage of G-CSF mobilized donor is correlated with the
      occurrence of aGVHD in the early stage after HSCT, the percentage of Tc2 in donor
      is negatively correlated with aGVHD morbidity in recipients.

PMID- 16584604
TI  - [Unrelated donor peripheral blood stem cell transplantation for hematologic
      malignancies].
AB  - This study was aimed to explore feasibility and efficacy of unrelated donor
      peripheral blood stem cell transplantation (UD-PBSCT) in treatment of hematologic
      malignancies. Ten patients with hematologic malignancies underwent high
      resolution DNA based typing HLA-matched or 1 locus mismatched UD-PBSCT. Busulfan,
      cyclophosphamide, Ara-C, MeCCNU and antithymocyte globulin (ATG) were used for
      preconditioning regimen in all cases. All patients received mycophenolate
      mofetile, cyclosporin A and short-term methotrexate with CD25 antibody as the
      graft-versus-host disease (GVHD) prophylaxis. The results showed that rapid
      engraftment was observed in all cases who presented full donor chimerism at 28
      days post transplantation by STR-PCR. The median time of neutrophil recovery >
      0.5 x 10(9)/L, platelet recovery > 20 x 10(9)/L was 13, 17.5 days respectively
      after transplantation. The incidence of acute GVHD was 3 cases (one case with
      grade I was recovered from GVHD by himself, one case with grade III was cured,
      one case with grade VI was died). It is concluded that above-mentioned
      preconditioning regimen and GVHD prophylaxis are effective approaches for
      unrelated donor peripheral blood stem cell transplantation in hematopoietic
      malignancies.

PMID- 16584605
TI  - [Correlative analysis between HLA high resolution typing and GVHD in 48 cases
      received unrelated umbilical cord blood transplantation].
AB  - Unrelated umbilical cord blood units for 54 cases in 21 transplant centers were
      provided by Guangzhou Cord Blood Bank in China from 1998 to 2003. This study was
      aimed to identify HLA-DRB1 alleles by means of PCR sequencing based typing
      methods (SBT) and to analyze the correlation between HLA-DRB1 alleles and GVHD in
      unrelated umbilical cord blood transplantation (UCBT). 48 out of 54 patients
      received UCBT were followed up. DNA were extracted from cryopreservation blood of
      recipients/donors with UCBT, HLA-DRB1 alleles typing were done by SBT. Compared
      with low resolution results of HLA-DRB1 alleles, high resolution results were
      analyzed to see any correlation between HLA-DRB1 alleles and GVHD. by double
      blind statistically analysis of HLA-DRB1 high resolution in 48 donor/recipient
      typings in UCBT. The results showed that the incidence of GVHD (25%) in patients
      who has HLA-DRB1 alleles matched with donors significantly lower (65.6%) than
      that in the patients with HLA-DRB1 alleles mismatched (P = 0.008). It is
      concluded that HLA-DRB1 by high resolution typing method is important in clinical
      application in UCBT.

PMID- 16584606
TI  - [CD4+ CD25high regulatory T cells in peripheral blood of patients with B cell non
      Hodgkin's lymphoma].
AB  - This study was aimed to analyze the proportion of T cell subsets, CD4(+)
      CD25(high) regulating T cells (Tr) in peripheral blood of B-NHL patients and
      their change regularity, and to investigate the immunosuppression mechanism and
      influence of chemotherapy on immunosuppression function of B-NHL patients. The
      peripheral blood was collected from 42 patients with B-NHL, 36 patients with B
      NHL who achieved partial remission (PR) or complete remission (CR) after 4 - 6
      cycles of chemotherapy and 15 healthy controls. By using monoclonal antibodies,
      the blood samples were evaluated with the flow cytometry for lymphocyte subsets
      and Tr cells. The results showed that the proportion of CD3(+) and CD4(+) T
      cells, and the ratio of CD4/CD8 in patients with B-NHL group was significantly
      less than those in the healthy controls, i.e. (68.33 +/- 15.27)% versus (72.06 +/
      9.26)%; (34.47 +/- 12.84)% versus (42.45 +/- 9.2)%; 1.36 +/- 0.26 versus 1.92 +/
      0.20, but the prevalence of the CD4(+) CD25(high) Tr cells was significantly
      higher than those in the healthy group [(4.10 +/- 1.21)% versus (2.04 +/- 1.03)%,
      P < 0.001]. The ratio of CD4/CD8 in chemotherapy group was lower than that in
      control, but the proportion of CD4(+) CD25(high) Treg cells in chemotherapy group
      was higher than those before chemo-/radio-therapy and the control. It is
      concluded that the relative increase of CD4(+) CD25(high) Tr cells in peripheral
      blood of B-NHL patients may be related to immunosuppression and tumor
      progression.

PMID- 16584607
TI  - [Establishment of purification procedure for recombinant fusion protein B7-2
      PE40KDEL].
AB  - This study was aimed to establish downstream purification procedure by which the
      protein of interest can be purified to higher purity rapidly and efficiently. The
      different combinations of various purification strategies, methods and conditions
      were compared, including reversed phase chromatography, metal chelating
      chromatography, anion exchange chromatography, blue dye affinity chromatography,
      filtration chromatography and so on. The results showed that in reversed phase
      chromatography, isolated protein of interest was denatured and precipitated
      immediately after chromatography because methanol or acetonitrile were adopted as
      the organic phase. In blue dye affinity chromatography expecting to purify the
      protein of interest in one step, protein of interest was difficultly
      differentiated from mixed protein as much proteins bound to the chromatography
      media by non-specific affinity. While there is a translation-enhancing sequence
      T7-g10 in the PRSETA-B7-2-PE40KDEL expression vector, so it adds 6 histidines to
      the N terminus of the protein of interest, this allows to purify the protein of
      interest by metal chelating chromatography. Based on this characteristic, a three
      step chromatography line including metal chelating chromatography, anion exchange
      chromatography and filtration chromatography was finally established after
      repeated experiments. By this way the purity of protein of interest reached 95%
      and the total recovery rate was 8%. The result of Western blot indicated that the
      expressed and purified recombinant B7-2-PE40KDEL could specifically bind with mAb
      against human B7-2 and multiple antibody against PEA. The cytotoxicity of the
      recombinant toxin tested by MTT method showed that the B7-2-PE40KDEL could
      selectively kill Jurkat cell line expressing CD28 receptor well and had no
      killing effect on the Raji cell line unexpressing CD28 receptor. It is concluded
      that a high efficient and speedy three-step purification procedure for the
      purifying recombinant protein B7-2-PE40KDEL was established, and this procedure
      possess selective killing activity on CD28 positive T lymphocytes.

PMID- 16584608
TI  - [Proliferation of natural killer T cells in umbilical cord blood and peripheral
      blood and their different phenotypes].
AB  - Purpose of this study was to establish an effective method in vitro to
      proliferate natural killer T (NKT) cells from umbilical cord blood (UCB) and
      peripheral blood (PB), and to study their different phenotype. Mononuclear cells
      (MNC) from UCB and PB were cultured in the presence of IL-2 (100 U/ml), with or
      without alpha-Galcer. TCR Valpha24 Vbeta11 double positive natural killer T-cells
      (NKT cells) and their other phenotypes were determined by flow cytometry. The
      results showed that after expansion for 7 days, TCRValphabeta(+) NKT cells from
      UCB-MNCs increased by (8.74 +/- 4.37) x 10(2) times as much, but most of them did
      not express NK1.1 and its TCR Vbeta11(+) was higher than TCR Valpha24(+). After
      expansion for 14 days, TCR Valphabeta(+) NKT cells from PB-MNCs increased by
      (3.72 +/- 2.01) x 10(2) times, the expression of NK1.1 was high and its TCR
      Vbeta11(+) was almost equal to TCR Valpha24(+). It is concluded that human TCR
      Valpha24 Vbeta11 double positive NKT cells can expand by addition of alpha
      Galcer. The proliferation efficiency in UCB-MNCs is greater than that in PB-MNCs.
      Most of the UCB-NKT is NK1.1(-), while the PB-NKT is NK1.1(+), a new subset of
      NKT cells.

PMID- 16584609
TI  - [Reference values of blood lymphocyte immunophenotype in the normal healthy
      adults of Ugyur and Han nationalities in Xinjiang].
AB  - This study was aimed to establish the reference values of blood lymphocyte
      immunophenotype in healthy adult between Ugyur and Han nationalities in Xinjiang
      and to compare the difference between these two nationalities in respect to
      nationality and gender, anticoagulated peripheral blood samples of 75 Ugyur
      people and 104 Han people were stained with monoclonal antibodies; the
      lymphocytes were analyzed by flow cytometry for the expression of lymphocyte
      population bearing surface markers, the data were analyzed by SPSS 11.0. The
      results showed that the reference ranges of blood lymphocyte subsets in Uygur and
      Han adults were as follows: total T cells amounted to 67.85 +/- 8.97% and 69.98
      +/- 10.14% respectively; helper T cell to 36.86 +/- 5.74% and 40.07 +/- 6.10%
      respectively; inhibitor T cell to 26.67 +/- 6.15% and 27.16 +/- 6.29%
      respectively; CD4/CD8 ratio to 1.46 +/- 0.47 and 1.56 +/- 0.47 respectively; NK
      cell to 16.91 +/- 9.89% and 12.81 +/- 7.34% respectively; B cell to 10.09 +/-
      3.33% and 11.78 +/- 3.81% respectively; CD3(+)/HLA-DR(+) to 10.05 +/- 2.95% and
      11.27 +/- 4.98% respectively; CD25(+) cell to 1.76 +/- 5.26% and 4.10 +/- 4.30%
      respectively. The differences of those two nationalities were mainly in total T
      cells, NK cell, B cell and CD25(+) cell. Furthermore there were also some
      differences between male and female. There might exist differences in helper T
      cells, CD4/CD8 ratio between Ugyur male and female, while this difference in Han
      lied in inhibitor cell and NK cell. Compared to those of two nationalities, the
      helper T cell percentage and CD4/CD8 ratio of Uygur male were lower than those in
      Han male. And in female, Uygur people had higher percent of NK cell (P < 0.01),
      but lower CD25(+) cell than those in Han's (P < 0.01). In conclusion, the
      nationalities and gender could influence the reference value of lymphocyte
      immunophenotype, the reference values of blood lymphocyte immunophenotype in the
      normal healthy adults of Ugyur and Han nationalities in Xinjiang were defined,
      and the differences between these two nationalities in respect to nationality and
      gender were elucidated.

PMID- 16584610
TI  - [In vitro cytokines-induced differentiation in mononuclear cell derived dendritic
      cells from chronic myeloid leukemia].
AB  - The purpose of this study was to investigate the mechanism of effects of
      interferon-alpha (IFN-alpha) on chronic myeloid leukemia (CML). Bone marrow
      mononuclear cells (BMMNC) were obtained from heparinized blood of CML patients by
      Ficoll-Paque density gradient centrifugation. The expressions of CD1a, CD83,
      CD86, HLA-ABC, HLA-DR and CD54 on DC induced by IFN-alpha + GM-CSF, IFN-alpha +
      GM-CSF+IL-4 and IL-4 + GM-CSF for 7 days in vitro were assayed by flow cytometry.
      The morphologic features were observed by transmission and optical microscopy.
      The mixed lymphocyte reactions (MLR) with DC were evaluated by MTT assay. The
      results showed that the DC cultured in different cytokine combinations expressed
      significantly higher levels of CD1a, HLA-ABC, HLA-DR, CD86, CD54, and CD83 than
      those in the precultured. The DC growing with IFN-alpha + GM-CSF expressed
      significantly higher levels of HLA-ABC, HLA-DR than those in GM-CSF + IL-4. The
      CD86 expression and MLR levels in IFN-alpha + GM-CSF + IL-4 increased
      significantly. The expression rate of DC antigens and MLR in the IFN resistant
      group significantly lower than those in the newly diagnosed and the effectively
      treated groups after at least 6 months of IFN-alpha treatment (P < 0.05). The DC
      from the IFN resistant group did not express significantly CD86 and MLR in IFN
      alpha + GM-CSF + IL-4 groups compared to those in the newly diagnosed and IFN
      effective treated groups. It is concluded that the BMMNC from CML cultured in
      combination with IFN-alpha and other cytokines can be induced into DC with
      typical morphologic and immunophenotypic characteristics. Addition of IFN-alpha +
      GM-CSF + IL-4 to DC cultures can significantly up-regulate the expression of
      major histocompatibility complex molecules, co-stimulatory molecules and various
      adhesion molecules. The deficiency of DC differentiation and function may play a
      role in the development of clinical resistance to IFN-alpha.

PMID- 16584612
TI  - [Analysis of LRP16 gene promoter activity].
AB  - The study was aimed to analyze the characteristics of LRP16 gene promoter and its
      activity in order to explore the possible regulation mechanism of LRP16 gene
      expression. A 2.6 kb genomic DNA sequence of LRP16 5'-end was obtained from NCBI
      by BLAST software. The 7 target sequences between 0.2 - 2.6 kb from a healthy
      blood donor DNA sample were amplified by PCR, then identified by DNA sequencing
      and semi-nest PCR. The verified sequences were analyzed on-line. The results
      showed that the 7 target sequences were about 400 bp different from each other.
      All 7 sequences were the same to these GenBank described. At last, all 7 promoter
      sequences were ligated with luciferase vector, and then the luciferase activity
      was analyzed in HeLa cells. A known gene promoter sequence can be freely obtained
      from NCBI database. It is concluded that LRP16 promoter is a standard type II
      promoter and its activity is strongest in the region from -200 to -600 bp.

PMID- 16584611
TI  - [HLA-DQA1 genotyping by using oligonucleotide microarrays].
AB  - In order to fabricate the HLA-DQA1 genotyping chip and develop an integrated,
      parallel technical platform to type HLA system, a pair of primers and a set of
      probes were designed according to the sequences of HLA-DQA1 exon 2, where the
      polymorphism is concentrated. The oligonucleotide chip was made with the methods
      developed in our laboratory. The target DNA was asymmetrically amplified with the
      labeled sense primer. The signals were scanned and analyzed after the
      hybridization between microarray and PCR product. The allele types of the samples
      were identified. The result was verified by the standard DNA and DNA sequencing.
      The results showed that the genotyping was successfully carried out in 50
      standard DNA samples and 50 clinical samples. Among them, results of the 50
      standard DNA samples matched their templates. In the other 50 samples, results of
      the randomly selected 10 matched their sequencing results except that two of them
      got the incompletely result. In reproducible tests, the signal reappear rate was
      95%. It is concluded that HLA-DQA1 genotyping by using our array system is simple
      and convenient with satisfied accuracy and reproducibility.

PMID- 16584614
TI  - [Process of human platelets loaded with rehalose before lyophilization].
AB  - The aim of this research was to study the technology and methods of loading
      lyoprotectant-trehalose into cytoplasm of human platelets before lyophilization,
      to optimize experimental conditions of loading trehalose, to investigate the
      changes of platelets response to agonists and activation after incubation of
      platelets for 4 hours at 37 degrees C in the presence of lyoprotectant-trehalose,
      to protract the figures of loading efficiency and intracellular trehalose
      concentration versus incubation time, temperature and external trehalose
      concentration, to optimize loading parameters. The response of platelets to
      different agonists--thrombin, ADP, collagen and ristocetin were measured
      respectively by APACT2 aggregometer before and after loading trehalose into
      platelets; the expressions of CD62p and PAC-1 on platelet membranes in the
      presence and absence of reversible platelets activation inhibitors were measured
      by flow cytometry respectively before and after loading trehalose into cytoplasm
      of platelets. The results showed that the loading efficiency was linear to
      incubation time (2 hours later) and incubation temperature (rang from 30 degrees
      C to 40 degrees C), respectively. The loading efficiency almost reached 60% when
      the platelets were incubated at 37 degrees C for 4 hours. The intracellular
      trehalose concentration was higher with the increase of the extracellular
      trehalose concentration (< 50 mmol/L). Compared to untreated groups, the values
      of MPV and aggregation to different agonists in treated groups showed no
      significant difference, respectively (P > 0.01). After incubation of platelets
      for 4 hours, the expression of CD62p increased to some extent, however, the
      expression of CD62p decreased again when the reversible platelets activation
      inhibitor PGE-1 and adenosine were added to the incubation buffer. It is
      concluded that 37 degrees C, 4 hours and the extracellular trehalose
      concentration < 50 mmol/L are the optimal conditions for loading with trehalose.
      The processing of loading with trehalose before platelet lyophilization has no
      significant effects on response of platelets to agonists and activation.

PMID- 16584613
TI  - [Preliminary study on xenotransfusion from porcine red blood cell into Rhesus
      monkey].
AB  - In order to study the possibility of xenotransfusion from porcine red blood cell
      (pRBC) to primate, the antigens on pRBC surface were modified to make it more
      compatible to primate sera. Porcine RBCs were subjected to both enzymatic removal
      of membrane alpha-Gal antigens with recombinant alpha-galactosidase (AGL) and
      covalent attachment of succinimid propionate-linked methoxypolyethyleneglycol
      (mPEG-SPA) to camouflage non-alphaGal antigens. The effects of double
      modifications were determinated by hemagglutination and clinical cross-match
      testing with rhesus sera. In vivo clearance rates and safety of modified pRBCs
      were measured after it was transfused into Rhesus monkey with or without
      immunosuppressant treatment. The validity of pRBC was detected in exsanguine
      Rhesus monkey model. The results showed that AGL could effectively remove alpha
      Gal xenoantigens on pRBC membrane and reduce hemagglutination. The combination of
      mPEG modification with AGL treatment could significantly increased compatibility
      between pRBCs and Rhesus monkey sera. Modified pRBCs were detectable in Rhesus
      monkey blood at 12 hours after transfusion, and their survival time was 40 hours
      in the immunosuppressant-treated Rhesus monkey. In vivo survival rates of pRBCs
      were 38% in exsanguine Rhesus monkey at 8 hours after transfusion, and during
      that time, the hemoglobin and hematocrit of Rhesus monkey were maintained at the
      same level as before it lost blood. It is concluded that the modified pRBC can be
      safely transfused into Rhesus monkey and relieve the anemic symptom exsanguine
      Rhesus monkey. It suggested that pRBC can be hopefully used as a blood substitute
      for primate and human in the future.

PMID- 16584616
TI  - [Correlation of thrombosis with increased platelet turnover in essential
      thrombocythemia].
AB  - This study was aimed to investigate the correlation of thrombosis with increased
      platelet turnover in essential thrombocythemia. According to presence or absence
      of thrombosis, 26 patients with ET were divided into two groups. Reticulated
      platelets (RP) were measured by flow cytometry and 26 healthy volunteers were
      selected as healthy controls. The ET patients with thrombosis were treated with
      hydroxyurea and interferon-alpha. The results demonstrated that the ET patients
      with thrombotic events had a significantly higher RP percentage (14.8% +/- 7.2%)
      than that in both asymptomatic ET patients (4.5% +/- 2.3%) and normal control
      (3.3% +/- 1.5%), (P < 0.05); the RP percentage in asymptomatic ET patients did
      not differ significantly from controls. ET patients with thrombosis also had a
      significantly higher absolute RP (ARP) count than those in ET patients without
      thrombosis [(176 +/- 37) x 10(9)/L vs (46 +/- 12) x 10(9)/L]. The ET patients
      with thrombosis were successfully treated with hydroxyurea plus INF-alpha, the RP
      percentage and ARP counts obviously reduced. In conclusion, when the ET patients
      had thrombotic events, those patients had a significantly higher RP percentage
      and ARP compared with patients without thrombosis and healthy controls. The ET
      patients with thrombosis were successfully treated with hydroxyurea plus INF
      alpha.

PMID- 16584615
TI  - [Biological activities of the coagulation factor VIII, IX in platelet
      concentrates collected by platelet apheresis during preservation].
AB  - The study was to explore the change of coagulation factor VIII and IX activities
      in the platelet suspension collected by platelet apheresis during storage at 22
      degrees C. 18 samples of platelet concentrates were collected by the cs-3000 plus
      and stored at 22 degrees C and then FVIII: C, FIX: C activities were detected at
      0, 12, 24, 48, 72, 96, 120 hours respectively by SYSMEX CA-1500. The results
      showed that FVIII: C activity was (100.51 + 44.02)% at 0 hour, and then decreased
      dramatically to 10% - 40% of primary level from 12 to 120 hours, while FIX: C
      activity was (120.93 +/- 20.50)% at 0 hour and decreased to 10% - 35% of primary
      level from 24 to 120 hours. In conclusion, FVIII and FIX in the platelet
      concentrates stored at 22 degrees C could keep their biological activities at
      physiologically high levels.

PMID- 16584617
TI  - [Comparison between protein detection methods for two-dimensional gel
      electrophoresis].
AB  - The aim of this study was to compare and analyze protein staining in order to
      select the optimal staining method for proteomic research. Proteins from acute
      promyelocytic leukemia cell line NB4 and protein molecular weight marker were
      separated respectively by 2-D or 1-D electrophoresis and detected respectively by
      the typical Coomassie brilliant blue, the colloidal Coomassie brilliant blue, the
      modified Coomassie brilliant blue and the silver staining protocols. The protein
      detection sensitivity, compatibility with mass spectrometry (MS) and facility of
      the four staining protocols were compared. The results indicated that the silver
      staining exhibited the highest sensitivity and MS showed the lowest compatibility
      10% of protein identification rate. The detection sensitivity of the modified
      Coomassie brilliant blue staining was superior to that of other two Coomassie
      brilliant blue stainings, close to but lower than the silver staining, however
      the compatibility with MS was better (protein identification rate about 55%). It
      is concluded that the protein detection sensitivity of the modified Coomassie
      brilliant blue staining is high, and its compatibility with MS is better, this
      modified Coomassie brilliant blue staining is an optimal staining method for
      proteomic research.

PMID- 16584618
TI  - [Exploration of tumor-like hyperplasia in extramedullary hematopoietic tissue of
      beta-thalassanemia patients].
AB  - To investigate the morphological features of mediastinal extramedullary
      hematopoietic tissue in beta-thalassanemia patients and its diagnosis, the
      morphological features of tumor-like hyperplastic in extramedullary hematopoietic
      tissue were analyzed by using fine needle aspiration cytological (FNAC) biopsy
      and compared with bone marrow smear sample. The results indicated that in the
      FNAC smears of mediastinal tumor, neutrophilic myelocyte, neutrophilic
      metamyelocyte, neutrophilic stab granulocyte and neutrophilic segmented
      granulocyte were observed in granulocytic series; early normoblast, polychromatic
      normoblast and orthochromatic normoblast were observed in erythrocytic series;
      and granular megakaryocyte, thromocytogenic megakaryocyte, scattered platelet and
      matured lymphocyte also were observed. Cell morphology and distribution in
      different stages were are similar to that in bone marrow smear, and these cells
      belong to the extra-medullary hemopoietic tissue. It is concluded that tumor-like
      hyperplasia in extra-medullary hemopoietic tissue of beta-thalassanemia patient
      is a rare phenomenon, FNAC detection is a quick, convenient and effective method
      for its diagnosis.

PMID- 16584619
TI  - [Curative effect of interleukin 11 on chronic idiopathic thrombocytopenic
      purpura].
AB  - The aim of this study was to investigate the circulating levels of IL-11 in the
      patients with chronic idiopathic thrombocytopenic purpura (CITP), and its
      significance, and to evaluate the curative effect of rhIL-11 on CITP. The level
      of IL-11 in patients with CITP was determined by ELISA before and after
      treatment, respectively. 1.5 mg of rhIL-11 were injected subcutaneously, once a
      day, continuously for 14 days as one course, treatment time 1 - 2 courses as
      total. The results showed that the higher blood IL-11 level was found in CITP
      patients than that in controls (P < 0.01) and during the course of treatment the
      number of platelets in peripheral blood of patients with CITP parallelled to the
      level of IL-11. The platelet counts were obviously increased in all CITP patients
      after rhIL-11 treatment. It is concluded that the serum level of IL-11 in
      patients is correlated to the number of platelets in patients. rhIL-11 can be
      used as an effective treatment for CITP.

PMID- 16584620
TI  - [Progress of research and application on hematopoietic stem cell transplantation
      by intra-bone marrow injection--review].
AB  - The purpose of hematopoietic stem cell transplantation by intra-bone marrow
      injection (IBM-HSCT) is to facilitate the homing of HSC. It has been recently
      proven in many animal experiments that different kinds of donor cells could
      efficiently home and engraft into the bone marrow by IBM-HSCT, which led to the
      rapid hemopoietic and immune recovery of recipients, preventing the development
      of GVHD, inducing the donor-specific tolerance in allogeneic organ
      transplantation, and promoting the survival rate of recipients. In this review,
      the effect of IBM-BMT and IBM-UCBT, the application of IBM injection technique in
      the study on HSC's biological characteristics, and its prospect for clinical HSCT
      were summarized.

PMID- 16584621
TI  - [Regulation mechamion of mesenchymal stem cells to immunoeffector cells--review].
AB  - Mesenchymal stem cells have two main properties: self renewal and the ability to
      differentiate multiple lineage. Because MSCs exhibit low immunogenicity and
      demonstrate significant suppressive activity in cell cultures containing
      alloreactive T cells, they play an important role in transplantation immunology,
      but the exact mechanism remains unknown. This article focuses on the
      immunoregulatory feature of MSCs to immunoeffector cells, such as T cells, B
      cells, and NK cells. The role of MSC in transplantation immunoregulation,
      regulatory mechanism of MSC in cellular immunity (direct contact of cells with
      cells, apoptosis and immunoregulation of MSC on lymphocytes), immunoregulation of
      MSC on DC and NK cells were reviewed.

PMID- 16584622
TI  - [Mesenchymal stem cells in hematopoietic regulation--review].
AB  - As the progenitor of most cell components in the hematopoietic microenvironment,
      mesenchymal stem cells (MSC) exhibit self-renewal and multilineage
      differentiation capacity. Through direct interaction with hematopoietic cells,
      secreting extracellular matrix and factors, MSC maintain the integrity of
      hematopoietic microenvironment and regulate hematopoiesis accurately. This review
      summarized the function of MSC in hematopoietic regulation, such as secretion of
      cytokines supporting hematopoiesis, MSC expression and adhesion molecules
      interacting with hematopoietic cells, and supportive effects of transplantation
      combining MSC with HSC on hematopoietic reconstruction, and its clinical
      perspectives.

PMID- 16584623
TI  - [Progress in the study of lyophilization of human red blood cells--review].
AB  - Now the clinical preservation methods of human red blood cells mainly include
      hypothermic storage (4 degrees C) and cryopreservation (-80 degrees C or -196
      degrees C). The preservation time of hypothermic storage of red blood cells is
      relatively short and it is easy to be contaminated by microbes. Cryopreservation
      greatly prolongs the storage time, but it needs heavy storage equipments. Because
      the protective solutions in cryopreservation contain glycerol, red blood cells
      need complicated washing in order to remove glycerol. These shortage methods
      limit their application to some special conditions, such as war or natural
      disasters. Compared with conventional preservation methods of red blood cells,
      lyophilization has many advantages such as less weight, convenient
      transportation, room temperature preservation, prone to be rehydrated. In this
      review, the progress and challenge in the development of lyophilization of red
      blood cells, especially application of trehalose and its mechanism in the
      lyophilization of red blood cells were systematically discussed. This review can
      provide some theoretic guidance for developing a safe, simple and efficient
      preservation approach of red blood cells by lyophilization.

PMID- 16584624
TI  - [Thrombin and angiogenesis of cancer--review].
AB  - Thrombin is the most important factor in hemostasis. In recent years, it has been
      found that thrombin is a potent mitogen capable of inducing cellular functions.
      Therefore, it is proved to be of importance in promoting the growth, metastasis
      and angiogenesis of cancer. Anticoagulant therapy not only reduce the
      characteristic hypercoagulability of cancer, but also inhibits growth and
      metastasis of cancer, and alters the fundamental biology of cancer. In this paper
      thrombin and its receptor, relationship of thrombin and its receptor with cancer
      growth, metastasis and angiogenesis, the mechanisms of thrombin influence on
      cancer angiogenesis, as well as application prospects on anti-angiogenesis and
      anti-coagulation therapy were reviewed.

PMID- 16584625
TI  - Sphingosine kinase: biochemical and cellular regulation and role in disease.
AB  - Sphingolipids have emerged as molecules whose metabolism is regulated leading to
      generation of bioactive products including ceramide, sphingosine, and sphingosine
      1-phosphate. The balance between cellular levels of these bioactive products is
      increasingly recognized to be critical to cell regulation; whereby, ceramide and
      sphingosine cause apoptosis and growth arrest phenotypes, and sphingosine-1
      phosphate mediates proliferative and angiogenic responses. Sphingosine kinase is
      a key enzyme in modulating the levels of these lipids and is emerging as an
      important and regulated enzyme. This review is geared at mechanisms of regulation
      of sphingosine kinase and the coming to light of its role in disease.

PMID- 16584626
TI  - Vascular endothelial cadherin-mediated cell-cell adhesion regulated by a small
      GTPase, Rap1.
AB  - Vascular endothelial cadherin (VE-cadherin), which belongs to the classical
      cadherin family, is localized at adherens junctions exclusively in vascular
      endothelial cells. Biochemical and biomechanical cues regulate the VE-cadherin
      adhesive potential by triggering the intracellular signals. VE-cadherin-mediated
      cell adhesion is required for cell survival and endothelial cell deadhesion is
      required for vascular development. It is therefore crucial to understand how VE
      cadherin-based cell adhesion is controlled. This review summarizes the inter
      endothelial cell adhesions and introduces our recent advance in Rap1-regulated VE
      cadherin adhesion. A further analysis of the VE-cadherin recycling system will
      aid the understanding of cell adhesion/deadhesion mechanisms mediated by VE
      cadherin in response to extracellular stimuli during development and
      angiogenesis.

PMID- 16584627
TI  - Purification and characterization of a deoxyriboendonuclease from Mycobacterium
      smegmatis.
AB  - A deoxyriboendonuclease has been purified to near homogeneity from a fast growing
      mycobacterium species, M. smegmatis and characterized to some extent. The size of
      enzyme is about 43 kDa as determined by a denaturing gel analysis. It shows
      optimum activity at 32 degrees C in Tris-HCl buffer (pH 7.2) containing 2.5 mM of
      MgCl2. Both EDTA and K+ but not Na+ inhibit its activity. Evidences show that the
      enzyme is not a restriction endonuclease but catalyzes the endonucleolytic
      cleavage of both the double- as well as the single-strand DNA non-specifically.
      It has been shown that the cleavage by this enzyme generates DNA fragments
      carrying phosphate groups at 5' ends and hydroxyl group at the 3' ends,
      respectively. Analysis reveals that no endonuclease having size and property
      identical to our deoxyriboendonuclease had been purified from M. smegmatis
      before. The property of our enzymes closely matches with the
      deoxyriboendonucleases purified from diverse sources including bacteria.

PMID- 16584628
TI  - Maltol inhibits apoptosis of human neuroblastoma cells induced by hydrogen
      peroxide.
AB  - To analyze the effect of Maltol on the apoptosis of Human Neuroblastoma Cells (SH
      SY5Y) treated by free radical which was generated from Hydrogen Peroxide (H2O2),
      flow cytometry analysis on Phosphatidylserine (PS) inverting percentage was
      applied to determine the apoptosis. MTT (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide) assay was employed to analyze the cell viability. DNA
      electrophoresis was used to detect DNA fragmentation. Moreover intracellular
      calcium of concentration ([Ca2+]i) was measured by fluorescence emission. Flow
      cytometry analysis on the function of mitochondria and Western blot analysis of
      NF-kappaB. The results showed that the pretreatment with maltol for 2 hours could
      prevent the H2O2-induced apoptosis. Maltol could reduce the inverting percentage
      of PS, DNA fragmentation and [Ca2+]i, and enhance the cellular function of
      mitochondria. NF-kappaB activated by H2O2 is reduced. The experiments suggest
      that maltol could effectively inhibit the apoptosis induced by H2O2. As a novel
      anti-oxidant, maltol is a new promising drug in protecting the neurological cells
      from the damage by free radical.

PMID- 16584629
TI  - Substitution of serine for non-disulphide-bond-forming cysteine in grass carp
      (Ctenopharygodon idellus) growth hormone improves in vitro oxidative
      renaturation.
AB  - Native grass carp (Ctenopharygodon idellus) growth hormone, has 5 cysteine amino
      acid residues, forms two disulphide bridges in its mature form. Recombinant grass
      carp growth hormone, when over-expressed in E. coli, forms inclusion bodies. In
      vitro oxidative renaturation of guanidine-hydrochloride dissolved recombinant
      grass carp growth hormone was achieved by sequential dilution and stepwise
      dialysis at pH 8.5. The redox potential of the refolding cocktail was maintained
      by glutathione disulphide/glutathione couple. The oxidative refolded protein is
      heterogeneous, and contains multimers, oligomers and monomers. The presence of
      non-disulphide-bond-forming cysteine in recombinant grass carp growth hormone
      enhances intermolecular disulphide bond formation and also nonnative
      intramolecular disulphide bond formation during protein folding. The non
      disulphide-bond-forming cysteine was converted to serine by PCR-mediated site
      directed mutagenesis. The resulting 4-cysteine grass carp growth hormone has
      improved in vitro oxidative refolding properties when studied by gel filtration
      and reverse phase chromatography. The refolded 4-cysteine form has less
      hydrophobic aggregate and has only one monomeric isoform. Both refolded 4
      cysteine and 5-cysteine forms are active in radioreceptor binding assay.

PMID- 16584630
TI  - Molecular cloning, characterization and expression of a novel trehalose-6
      phosphate synthase homologue from Ginkgo biloba.
AB  - In many organisms, trehalose acts as protective metabolite against harsh
      environmental stresses, such as freezing, drought, nutrient starvation, heat and
      salt. Herein a cDNA (designated as GbTPS, GenBank Accession Number AY884150)
      encoding a trehalose-6-phosphate synthase homologue was isolated and
      characterized from the living fossil plant, Ginkgo biloba, which is highly
      tolerant to drought and cold. GbTPS encoded an 868-amino-acid polypeptide with a
      predicted isoelectric point of 5.83 and molecular mass of 97.9 kD. Amino acid
      sequence alignment revealed that GbTPS shared high identity with class II
      trehalose-6-phosphate synthase homologues (67% identical to AtTPS7), but had only
      17% and 23% of identity with OstA from Escherichia coli and ScTPS1 from S.
      cerevisiae, respectively. DNA gel blot analysis indicated that GbTPS belonged to
      a small multi-gene family. The expression analysis by RT-PCR showed that GbTPS
      expressed in a tissue-specific manner in G. biloba and might involve in leaf
      development. GbTPS was also found to be induced by a variety of stresses
      including cold, salt, drought and mannitol.

PMID- 16584631
TI  - Transition state characterization of the low- to physiological-temperature
      nondenaturational conformational change in bovine adenosine deaminase by slow
      scan rate differential scanning calorimetry.
AB  - Bovine adenosine deaminase undergoes a nondenaturational conformational change at
      29 degrees C upon heating which is characterized by a large increase in heat
      capacity. We have determined the transition state thermodynamics of the
      conformational change using a novel application of differential scanning
      calorimetry (DSC) which employs very slow scan rates. DSC scans at the
      conventional, and arbitrary, scan rate of 1 degree C/min show no evidence of the
      transition. Scan rates from 0.030 to 0.20 degrees C/min reveal the transition
      indicating it is under kinetic control. The transition temperature T(t) and the
      transition temperature interval deltaT increase with scan rate. A first order
      rate constant k1 is calculated at each T(t) from k1 = r(scan)/deltaT, where
      r(scan) is the scan rate, and an Arrhenius plot is constructed. Standard
      transition state analysis reveals an activation free energy deltaG(double dagger)
      of 88.1 kJ/mole and suggests that the conformational change has an unfolding
      quality that appears to be on the direct path to the physiological-temperature
      conformer.

PMID- 16584632
TI  - Preliminary proteomic analysis of indomethacin's effect on tumor transplanted
      with colorectal cancer cell in nude mice.
AB  - Nonsteroidal anti-inflammatory drugs such as indomethacin (IN) can exert anti
      colorectal cancer (CRC) activity through cyclooxygenase independent mechanism,
      but the exactly biological mechanism is not completely known. Here we use
      proteomic tools to investigate the molecular mechanism of this action. First,
      nude mice bearing tumors derived from subcutaneous injection with human CRC cell
      line HCT116 were randomly allocated to groups treated with or without
      indomethacin. Later, tumor lumps were incised and then total proteins extracted.
      After separated with two-dimensional electrophoresis, thirty-one differently
      expressed spots were found between IN-treated and non-IN-treated groups, of which
      25 spots decreased and 6 spots increased in abundance in IN-treated group.
      Through matrix-assisted laser desorption ionization time of flight mass
      spectrometry and then NCBInr and SWISS-PROT databases searching, 12 protein spots
      were finally identified including galectin-1, annexin A1, annexin IV,
      transcription factor BTF3A, calreticulin. Most of the identified proteins are
      correlated with tumor's biological properties of proliferation, invasion,
      apoptosis and immunity, or take part in cell's signal transduction. From above we
      thought that indomethacin can exert its effect on colorectal cancer through
      regulating several proteins' expression directly or indirectly. Further study of
      these proteins may be helpful in founding new targets of drugs for cancer
      chemotherapy.

PMID- 16584633
TI  - Structure analysis of 16S rDNA sequences from strains of Acidithiobacillus
      ferrooxidans.
AB  - Four strains of Acidithiobacillus ferrooxidans with different iron oxidation
      capacity were isolated from different mine drainage stations. The 16S rRNA gene
      of these strains were cloned and sequenced. Based on our sequences analysis on
      the four strain and the data on the other strains deposited in Genbank, all A.
      ferrooxidans may be classified into three phylogenetic groups. The analysis data
      showed that nucleotide variables (signature sites) were detected in 21 positions,
      and most of them were found in the first 800 bp from 5' terminal except position
      970 and 1375. Interestingly, the first 13 signature sites were located in two
      main regions: the first region (position 175-234) located in V2 while the second
      region (position 390-439) were detected in constant region between V2 and V3.
      Furthermore, the secondary structure and minimal free energy were determined in
      two regions among strains of three groups. These results may be useful in
      characterizing the microevolutionary mechanisms of species formation and
      monitoring in biohydrometallurgical application.

PMID- 16584634
TI  - Confirming single nucleotide polymorphisms from expressed sequence tag datasets
      derived from three cattle cDNA libraries.
AB  - Using the Phred/Phrap/Polyphred/Consed pipeline established in the National
      Livestock Research Institute of Korea, we predicted candidate coding single
      nucleotide polymorphisms (cSNPs) from 7,600 expressed sequence tags (ESTs)
      derived from three cDNA libraries (liver, M. longissimus dorsi, and intermuscular
      fat) of Hanwoo (Korean native cattle) steers. From the 7,600 ESTs, 829 contigs
      comprising more than two EST reads were assembled using the Phrap assembler.
      Based on the contig analysis, 201 candidate cSNPs were identified in 129 contigs,
      in which transitions (69%) outnumbered transversions (31%). To verify whether the
      predicted cSNPs are real, 17 SNPs involved in lipid and energy metabolism were
      selected from the ESTs. Twelve of these were confirmed to be real while five were
      identified as artifacts, possibly due to expressed sequence tag sequence error.
      Further analysis of the 12 verified cSNPs was performed using the program BLASTX.
      Five were identified as nonsynonymous cSNPs, five were synonymous cSNPs, and two
      SNPs were located in 3'-UTRs. Our data indicated that a relatively high SNP
      prediction rate (71%) from a large EST database could produce abundant cSNPs
      rapidly, which can be used as valuable genetic markers in cattle.

PMID- 16584635
TI  - Antibodies against nitric oxide damaged poly L-tyrosine and 3-nitrotyrosine
      levels in systemic lupus erythematosus.
AB  - Alterations in the amino acid structure or sequence can generate neo-epitopes
      from self-proteins causing autoaggressive immune attack. Reactive nitrogen
      species are an important factor that induces post-translational modification of
      proteins by cellular reduction and oxidation mechanism; cysteinyl-nitrosylation
      or tyrosine nitration leading to potentially pathogenic pathways. It was thought
      of interest to investigate the immunogenicity of nitrated poly L-tyrosine vis-a
      vis its possible role in the induction of antibodies in systemic lupus
      erythematosus (SLE). Commercially available poly L-tyrosine was exposed to
      nitrating species and the damage was monitored by UV spectroscopy and alkaline
      gel electrophoresis. The results indicated the formation of 3-nitrotyrosine.
      Nitrated poly L-tyrosine induced higher titre antibodies as compared to the
      native form. Nitrated poly L-tyrosine was recognized by the autoantibodies
      present in the sera of patients suffering from SLE by enzyme immunoassays and
      band shift assay. The possible role of nitrated self-proteins has been discussed
      in the production of circulating anti-DNA antibodies in SLE.

PMID- 16584636
TI  - Protective effect of a 43 kD protein from the leaves of the herb, Cajanus indicus
      L on chloroform induced hepatic-disorder.
AB  - Cajanus indicus is a herb with medicinal properties and is traditionally used to
      treat various forms of liver disorders. Present study aimed to evaluate the
      effect of a 43 kD protein isolated from the leaves of this herb against
      chloroform induced hepatotoxicity. Male albino mice were intraperitoneally
      treated with 2 mg/kg body weight of the protein for 5 days followed by oral
      application of chloroform (0.75 ml/kg body weight) for 2 days. Different
      biochemical parameters related to physiology and pathophysiology of liver, such
      as, serum glutamate pyruvate transaminase and alkaline phosphatase were
      determined in the murine sera under various experimental conditions. Direct
      antioxidant role of the protein was also determined from its reaction with
      Diphenyl picryl hydroxyl radical, superoxide radical and hydrogen peroxide. To
      find out the mode of action of this protein against chloroform induced liver
      damage, levels of antioxidant enzymes catalase, superoxide dismutase and
      glutathione-S-transferase were measured from liver homogenates. Peroxidation of
      membrane lipids both in vivo and in vitro were also measured as
      malonaldialdehyde. Finally, histopathological analyses were done from liver
      sections of control, toxin treated and protein pre- and post-treated (along with
      the toxin) mice. Levels of serum glutamate pyruvate transaminase and alkaline
      phosphatase, which showed an elevation in chloroform induced hepatic damage, were
      brought down near to the normal levels with the protein pretreatment. On the
      contrary, the levels of antioxidant enzymes such as catalase, superoxide
      dismutase and glutathione-S-transferase that had gone down in mice orally fed
      with chloroform were significantly elevated in protein pretreated ones. Besides,
      chloroform induced lipid peroxidation was effectively reduced by protein
      treatment both in vivo and in vitro. In cell free system the protein effectively
      quenched diphenyl picryl hydroxyl radical and superoxide radical, though it could
      not catalyse the breakdown of hydrogen peroxide. Post treatment with the protein
      for 3 days after 2 days of chloroform administration showed similar results.
      Histopathological studies indicated that chloroform induced extensive tissue
      damage was less severe in the mice livers treated with the 43 kD protein prior
      and post to the toxin administration. Results from all these data suggest that
      the protein possesses both preventive and curative role against chloroform
      induced hepatotoxicity and probably acts by an anti-oxidative defense mechanism.

PMID- 16584637
TI  - Immunohistochemical studies of human ribosomal protein S3 (rpS3).
AB  - The human ribosomal protein S3 (rpS3) was expressed in E. coli using the pET-15b
      vector and the monoclonal antibodies (mAbs) were produced and characterized. A
      total of five hybridoma cell lines were established and the antibodies recognized
      a single band of molecular weight of 33 kDa on immunoblot with purified rpS3.
      When the purified rpS3 was incubated with the mAbs, the UV endonuclease activity
      of rpS3 was inhibited up to a maximum of 49%. The binding affinity of mAbs to
      rpS3 determined by using a biosensor technology showed that they have similar
      binding affinities. Using the anti-rpS3 antibodies as probes, we investigated the
      cross-reactivities of various other mammalian brain tissues and cell lines,
      including human. The immunoreactive bands on Western blots appeared to be the
      same molecular mass of 33 kDa in all animal species tested. They also appear to
      be extensively cross-reactive among different organs in rat. These results
      demonstrated that only one type of immunologically similar rpS3 protein is
      present in all of the mammalian brain tissues including human. Furthermore, these
      antibodies were successfully applied in immunohistochemistry in order to detect
      rpS3 in the gerbil brain tissues. Among the various regions in the brain tissues,
      the rpS3 positive neurons were predominantly observed in the ependymal cells,
      hippocampus and stantia nigra pars compacta. The different distributions of rpS3
      in brain tissues reply that rpS3 protein may play an important second function in
      the neuronal cells.

PMID- 16584638
TI  - Solubilization of proteins from human lymph node tissue and two-dimensional gel
      storage.
AB  - In the present study, we compared six different solubilization buffers and
      optimized two-dimensional electrophoresis (2-DE) conditions for human lymph node
      proteins. In addition, we developed a simple protocol for 2-D gel storage.
      Efficient solubilization was obtained with lysis buffers containing (a) 8 M urea,
      4% CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate), 40 mM Tris
      base, 65 mM DTT (dithiothreitol) and 0.2% carrier ampholytes; (b) 5 M urea, 2 M
      thiourea, 2% CHAPS, 2% SB 3-10 (N-decyl-N,N-dimethyl-3-ammonio-1
      propanesulfonate), 40 mM Tris base, 65 mM DTT and 0.2% carrier ampholytes or (c)
      7 M urea, 2 M thiourea, 4% CHAPS, 65 mM DTT and 0.2% carrier ampholytes. The
      optimal protocol for isoelectric focusing (IEF) was accumulated voltage of 16,500
      Vh and 0.6% DTT in the rehydration solution. In the experiments conducted for the
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), best
      results were obtained with a doubled concentration (50 mM Tris, 384 mM glycine,
      0.2% SDS) of the SDS electrophoresis buffer in the cathodic reservoir as compared
      to the concentration in the anodic reservoir (25 mM Tris, 192 mM glycine, 0.1%
      SDS). Among the five protocols tested for gel storing, success was attained when
      the gels were stored in plastic bags with 50% glycerol. This is the first report
      describing the successful solubilization and 2D-electrophoresis of proteins from
      human lymph node tissue and a 2-D gel storage protocol for easy gel handling
      before mass spectrometry (MS) analysis.

PMID- 16584639
TI  - Activity of human dihydrolipoamide dehydrogenase is largely reduced by mutation
      at isoleucine-51 to alanine.
AB  - Dihydrolipoamide dehydrogenase (E3) belongs to the pyridine nucleotide-disulfide
      oxidoreductase family including glutathione reductase and thioredoxin reductase.
      It catalyzes the reoxidation of dihydrolipoyl moiety of the acyltransferase
      components of three alpha-keto acid dehydrogenase complexes and of the hydrogen
      carrier protein of the glycine cleavage system. Isoleucine-51 of human E3,
      located near the active disulfide center Cys residues, is highly conserved in
      most E3s from several sources. To examine the importance of this highly conserved
      Ile-51 in human E3 function, it was substituted with Ala using site-directed
      mutagenesis. The mutant was expressed in Escherichia coli and highly purified
      using an affinity column. Its E3 activity was decreased about 100-fold,
      indicating that the conservation of the Ile-51 residue in human E3 was very
      important to the efficient catalytic function of the enzyme. Its altered
      spectroscopic properties implied that conformational changes could occur in the
      mutant.

PMID- 16584640
TI  - Laparoscopic Heller-Dor operation for patients with achalasia.
AB  - BACKGROUND: Laparoscopic Heller cardiomyotomy and Dor fundoplication is the
      surgical procedure of choice for esophageal achalasia. The aim of this study was
      to investigate the clinical outcome of laparoscopic Heller-Dor procedure in our
      initial series of 25 patients with achalasia. METHODS: Between October 2003 and
      January 2006, a total of 25 patients with achalasia underwent laparoscopic Heller
      Dor operation. Among them, 9 were male and 16 were female with an average age of
      (41.5 +/- 5.1) years (21-66). All the patients received upper gastrointestinal
      series (barium swallow), esophagogastroscopy, esophageal manometry to exclude
      esophageal carcinoma and to confirm the diagnosis, and 21 patients also had 24
      hour ambulatory pH studies. All the patients were operated by laparoscopic
      modified Heller's myotomy with Dor fundoplication. In addition, 2 of them had
      combined laparoscopic cholecystectomy + excision of hepatic hemangioma and
      laparoscopic cholecystectomy, respectively. RESULTS: The average operating time
      was (110.6 +/- 12.9) minutes (range, 60-180), operative blood loss averaged (18.6
      +/- 7.1) ml (5-50), the median time to oral feeding was (1.6 +/- 0.4) days (1-4)
      and the median hospital stay was (12.6 +/- 1.2) days (10-20). There was no
      conversion to open surgery. Intraoperative mucosal perforation was encountered in
      six patients and was repaired in all of them by laparoscopic suture. All the
      patients had an uneventful recovery without postoperative complication. After a
      median follow-up of (10.6 +/- 7.2) months (1-27), 24 patients were asymptomatic
      and 1 had mild postoperative dysphagia. CONCLUSIONS: Laparoscopic Heller-Dor
      operation had the advantages of reduced compromise of the cardiopulmonary
      function, with less disruption of the supporting structures (phrenoesophageal
      membrane) of the antireflux mechanism, requiring simpler general anesthesia and
      providing excellent exposure permitting an easy fundoplication, less pain and
      reduced morbidity, shorter hospitalization and faster convalescence.

PMID- 16584641
TI  - Complications of cardiac resynchronization therapy in patients with congestive
      heart failure.
AB  - BACKGROUND: Previous clinical studies have suggested that patients with
      congestive heart failure and intraventricular conduction delay could benefit from
      cardiac resynchronization therapy (CRT). Implantation of left ventricular lead is
      a complex procedure with some potential for complications. This study was
      conducted to analyse the complications of CRT in patients with congestive heart
      failure. METHODS: Totally 117 patients, 86 males and 31 females, mean age of 53
      years, with congestive heart failure and intraventricular conduction delay were
      enrolled in this study. Venography was performed on all patients. Different types
      of coronary sinus leads were used to pace the left ventricle. RESULTS: Left
      ventricular lead was attempted to implant through coronary sinus for all the 117
      patients and was successfully implanted in 111 patients. The success rate was
      94.9%. Main complications rate was 6.8%, including coronary sinus dissection in 4
      patients, phrenic nerve stimulation required lead repositioning in 2 patients and
      lead dislodgement in 2 patients. CONCLUSIONS: It is feasible and safe to pace
      left ventricle through coronary sinus. However, there are some procedural
      complications.

PMID- 16584642
TI  - Optimization of atrioventricular delay by surface electrocardiography during dual
      chamber pacing.
AB  - BACKGROUND: Nominal atrioventricular (AV) interval in dual chamber pacemaker
      (DDD) is not the best AV delay in the majority of patients with atrioventricular
      block. To find a simple method for optimizing AV delay adjustment, we assessed
      surface electrocardiography (ECG) for optimizing AV delay during dual chamber
      pacing. METHODS: DDD pacemakers were implanted in 46 patients with complete, or
      almost complete, AV block. Optimal AV delay was achieved by programming an
      additional delay of 100 ms, to the width of intrinsic P wave or to the interval
      between pacing spike to the end of P wave on surface ECG. Left ventricular (LV)
      end diastolic and end systolic volumes, ejection fraction and diastolic
      parameters were measured by Doppler echocardiography during both nominal and
      optimal AV delay pacing. RESULTS: Compared to nominal AV delay setting, LV end
      diastolic volume increased [to (53.2 +/- 11.3) ml from (50.2 +/- 10.2) ml, P <
      0.05], end systolic volume decreased [to (26.1 +/- 9.0) ml from (27.9 +/- 8.2)
      ml, P < 0.05] during adjusted AV delay pacing, resulting in an increase in LV
      ejection fraction [to (68.2 +/- 5.3)% from (64.5 +/- 4.3)%, P < 0.05]. LV
      diastolic filling and isovolumic relaxation time were not significantly changed.
      CONCLUSION: Optimization of AV delay by surface ECG is a simple method to improve
      LV systolic function during dual chamber pacing.

PMID- 16584643
TI  - HLA-DRB genotype and specific IgE responses in patients with allergies to
      penicillins.
AB  - BACKGROUND: Because of the pivotal role of the human leukocyte antigen (HLA)
      class II molecules in regulating the immune response and their extensive
      polymorphism, it is not surprising that particular HLA class II alleles have been
      implicated in susceptibility to allergic diseases and in restriction of the IgE
      responses to a variety of allergens. We investigated the relationship between HLA
      DRB genotype and allergies to various penicillins and explored HLA-DRB
      restriction of IgE responses to these derivatives of penicillin. METHODS:
      Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies
      (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an
      allergy to penicillins and 101 healthy subjects without any allergic reaction.
      Some (113 patients and 87 healthy control subjects) were chosen from all subjects
      to type for HLA-DRB alleles by sequence specific primer-polymerase chain
      reaction. RESULTS: Compared with control subjects, a significantly increased
      frequency of DR9 was present in 77 patients with allergic reactions, with
      immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P =
      0.005 respectively). Conversely, a significantly decreased frequency of DR14.1
      was found in 80 patients with positive IgE antibodies, with immediate reaction
      and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038).
      A possible excess of HLA-DR17 was found in subjects who were responsive to
      benzylpenicilloyl compared with those were not (chi(2) = 5.134, P = 0.023), and
      of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA,
      chi(2) = 4.057, P = 0.044). CONCLUSION: HLA-DRB gene may be involved in allergy
      to penicillins through modulating specific serum IgE to penicillins.

PMID- 16584645
TI  - BPI700-Fc gamma1(700) chimeric gene expression and its protective effect in a
      mice model of the lethal E. coli infection.
AB  - BACKGROUND: Infections caused by gram-negative bacteria (GNB) often lead to high
      mortality in common clinical settings. The effect of traditional antibiotic
      therapy is hindered by drug-resistant bacteria and unneutralizable endotoxin. Few
      effective methods can protect high risk patients from bacterial infection. This
      study explored the protection of adeno-associated virus 2 (AAV2)-bacteriacidal
      permeability increasing protein 700 (BPI(700))-fragment crystallizable gamma one
      700 (Fc gamma1(700)) chimeric gene transferred mice against the minimal lethal
      dose (MLD) of E. coli and application of gene therapy for bacterial infection.
      METHODS: After AAV2-BPI(700)-Fc gamma1(700) virus transfection, dot blotting and
      Western blotting were used to detect the target gene products in Chinese hamster
      ovary-K1 cells (CHO-K1cells). Reverse transcription-polymerase chain reaction and
      immunohistochemical assay were carried out to show the target gene expression in
      mice. Modified BPI-enzyme linked immunosorbent assay was used to identify the
      target gene products in murine serum. The protection of BPI(700)-Fc gamma1(700)
      gene transferred mice was examined by survival rate after MLD E. coli challenge.
      Colony forming unit (CFU) count, limulus amebocyte lysate kit and cytokine kit
      were used to quantify the bacteria, the level of endotoxin, and proinflammatory
      cytokine. RESULTS: BPI(1-199)-Fc gamma1 protein was identified in the CHO-K1 cell
      culture supernatant, injected muscles and serum of the gene transferred mice.
      After MLD E. coli challenge, the survival rate of AAV2-BPI(700)-Fc gamma1(700)
      gene transferred mice (36.7%) was significantly higher than that of AAV2-enhanced
      green fluorescent protein (AAV2-EGFP) gene transferred mice (3.3%) and PBS
      control mice (5.6%). The survival rate of AAV2-BPI(700)-Fc gamma1(700) gene
      transferred mice treated with cefuroxime sodium was 65.0%. The bacterium number
      in main viscera, the levels of endotoxin and proinflammatory cytokine (tumor
      necrosis factor-alpha and interleukin-1beta) in serum of the AAV2-BPI(700)-Fc
      gamma1(700) gene transferred mice were markedly lower than that of PBS control
      mice (P < 0.01). CONCLUSIONS: AAV2-BPI(700)-Fc gamma1(700) gene transferred mice
      can resist MLD E. coli infection through expressing BPI(1-199)-Fc gamma1 protein.
      Our findings suggested that AAV2 mediated BPI(700)-Fc gamma1(700) gene delivery
      could be used for protection and treatment of clinical GNB infection in high-risk
      individuals.

PMID- 16584644
TI  - Diagnostic value of contrast-enhanced fluid-attenuated inversion-recovery MRI for
      intracranial tumors in comparison with post-contrast T1W spin-echo MRI.
AB  - BACKGROUND: Contrast-enhanced fluid-attenuated inversion-recovery (FLAIR)
      magnetic resonance imaging (MRI) has been reported to have higher sensitivity for
      detecting leptomeningeal disease compared with contrast-enhanced T1-weighted MRI
      (CE T1WI). However, currently there are no studies showing the potential value of
      clinical applications of contrast-enhanced FLAIR (CE FLAIR) sequence in
      diagnosing intracranial tumors in a larger group of patients. The purpose of this
      study was to evaluate the diagnostic value of CE FLAIR in comparison with CE T1WI
      for intracranial tumors and to provide more information for clinical diagnosis
      and therapy. METHODS: One hundred and four consecutive cases of intracranial
      tumors referred for CE brain MRI were analyzed with regard to FLAIR and T1WI pre-
      and post-administration of Gd-DTPA. The CE FLAIR and CE T1WI were evaluated
      independently by two radiologists for the number of examinations with one or more
      enhanced lesions, the number and location of enhanced lesions per examination,
      signal-to-noise ratio (SNR) and contrast-enhancement ratio (CER) of lesions, as
      well as the size and extent of the enhanced lesions. RESULTS: In 98 of 104 cases,
      enhanced lesions were seen both on the FLAIR and T1W images. More lesions were
      seen on CE T1WI (n = 120) than those on CE FLAIR sequence (n = 117), but no
      differences of statistical significance were found between the two sequences (P >
      0.05). Four lesions were revealed only on the CE FLAIR images whereas 7 lesions
      were only found on CE T1WI. Enhanced lesions located in the cerebral hemisphere
      or the forth ventricle were revealed much more on CE T1WI than on CE FLAIR
      images. However, CE FLAIR images may be useful in showing superficial
      abnormalities and those located in the sulcus or lateral ventricle. The CER and
      contrast-to-noise ratio (CNR) on CE T1WI was significantly higher (t = 7.10, P =
      0.00; t = 9.67, P = 0.00, respectively), but grey matter/white matter contrast
      was lower (t = 2.46, P = 0.02) than those on CE FLAIR images. The SNR did not
      show any statistically significant difference between the two sequences (t = 1.1,
      P = 0.27). The size and extent of lesions on the CE FLAIR images were
      significantly larger than those on CE T1WI (t = 4.13, P = 0.00). CONCLUSIONS: CE
      FLAIR and CE T1WI may complement each other in showing intracranial tumors and
      the CE FLAIR sequence should be selected as a routine MRI sequence.

PMID- 16584646
TI  - Establishment of submandibular gland allotransplantation model in miniature
      swine.
AB  - BACKGROUND: Autologous transplantation of the submandibular gland (SMG) into the
      temporal fossa with microvascular anastomosis has been successfully applied in
      severe xerophthalmia patients as a permanent tear substitute. However, severe
      xerophthalmia can be accompanied by salivary gland dysfunction, making such
      autotransplantation unsuitable. Therefore, SMG allotransplantation might be a
      solution. The aim of this study was to assess the technical feasibility of
      submandibular gland allotransplantation. METHODS: Twelve miniature swine were
      randomized to serve as donors or recipients. One SMG was transplanted between a
      donor and a recipient. The donor SMG was revascularized by microvascular
      anastomosis of its vascular pedicle to the recipient lingual artery and external
      jugular vein. The secretory duct was implanted into the vestibule of the mouth
      through a subcutaneous tunnel. No immunosuppressive agent was administered. The
      results were assessed by visual inspection of the secretion, and
      histopathological examination of the transplanted SMG. RESULTS: Technically, all
      surgical procedures were successful. Clear secretion flowed out of the duct as
      soon as blood supply of the transplanted submandibular gland was reestablished.
      The secretion of the gland lasted for 5 days. As expected, an acute rejection
      reaction occurred after surgery because no immunosuppressive agents were used.
      Secretion from the transplanted SMG ceased within 5 days. CONCLUSIONS: A model of
      SMG allotransplantation can be established in miniature swine. The technique of
      submandibular gland allotransplantation is feasible.

PMID- 16584648
TI  - A resistin binding peptide selected by phage display inhibits 3T3-L1 preadipocyte
      differentiation.
AB  - BACKGROUND: Resistin, a newly discovered cysteine-rich hormone secreted mainly by
      adipose tissues, has been proposed to form a biochemical link between obesity and
      type 2 diabetes. However, the resistin receptor has not yet been identified. This
      study aimed to identify resistin binding proteins/receptor. METHODS: Three cDNA
      fragments with the same 11 bp 5' sequence were found by screening a cDNA phage
      display library of rat multiple tissues. As the reading frames of the same 11 bp
      5' sequence were interrupted by a TGA stop codon, plaque lift assay was
      consequently used to prove the readthrough phenomenon. The stop codon in the same
      11 bp 5' sequence was replaced by tryptophan, and the binding activity of the
      coded peptide [AWIL, which was designated as resistin binding peptide (RBP)] with
      resistin was identified by the confocal microscopy technique and the affinity
      chromatography experiment. pDual GC-resistin and pDual GC-resistin binding
      peptide were co-transfected into 3T3-L1 cells to confirm the function of resistin
      binding peptide. RESULTS: Three cDNA fragments with the same 11 bp 5' sequence
      were found. The TGA stop codon in reading frames of the same 11 bp 5' sequence
      was proved to be readthroughed. The binding activity of RBP with resistin was
      consequently identified. The expression of the resistin binding peptide in 3T3-L1
      preadipocytes expressing pDual GC-resistin significantly inhibited the adipogenic
      differentiation. CONCLUSION: RBP could effectively rescue the promoted
      differentiation of resistin overexpressed 3T3-L1 preadipocyte.

PMID- 16584647
TI  - Screening for glutamate-induced and dexamethasone-downregulated epilepsy-related
      genes in rats by mRNA differential display.
AB  - BACKGROUND: It is known that excessive release of glutamate can induce
      excitotoxicity in neurons and lead to seizure. Dexamethasone has anti-seizure
      function. The aim of this study was to investigate glutamate-dexamethasone
      interaction in the pathogenesis of epilepsy, identify differentially expressed
      genes in the hippocampus of glutamate-induced epileptic rats by mRNA differential
      display, and observe the effects of dexamethasone on these genes expression.
      METHODS: Seizure models were established by injecting 5 microl (250
      microg/microl) monosodium glutamate (MSG) into the lateral cerebral ventricle in
      rats. Dexamethasone (5 mg/kg) was injected intraperitoneally at 30 minutes after
      MSG inducing convulsion. The rats' behavior and electroencephalogram (EEG) were
      then recorded for 1 hour. The effects of dexamethasone on gene expression were
      observed in MSG-induced epileptic rats at 1 hour and 6 hours after the onset of
      seizure by mRNA differential display. The differentially expressed genes were
      confirmed by Dot blot. RESULTS: EEG and behaviors showed that MSG did induce
      seizure, and dexamethasone could clearly alleviate the symptom. mRNA differential
      display showed that MSG increased the expression of some genes in epileptic rats
      and dexamethasone could downregulate their expression. From more than 10
      differentially expressed cDNA fragments, we identified a 226 bp cDNA fragment
      that was expressed higher in the hippocampus of epileptic rats than that in the
      control group. Its expression was reduced after the administration of
      dexamethasone. Sequence analysis and protein alignment showed that the predicted
      amino acid sequence of this cDNA fragment kept 43% identity to agmatinase, a
      member of the ureohydrolase superfamily. CONCLUSIONS: The results of the current
      study suggest that the product of the 226 bp cDNA has a function similar to
      agmatinase. Dexamethasone might relax alleviate seizure by inhibiting expression
      of the gene.

PMID- 16584649
TI  - Expression of tissue inhibitor of matrix metalloproteinase-1 in aging of
      transgenic mouse liver.
AB  - BACKGROUND: Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is related to
      the aging of many organs, but few data are available on the change of TIMP-1 in
      liver aging. The purpose of this study was to investigate the expression and role
      of TIMP-1, matrix metalloproteinase-2 (MMP-2) and MMP-9 in the process of natural
      aging in the livers of normal and transgenic mice, and to detect the effects of
      TIMP-1 on oxidative level and anti-oxidative ability of the livers of transgenic
      young mice. METHODS: Normal and transgenic mice were divided into 3 groups
      according to their age: 3-month-old group (n = 5), 12-month-old group (n = 5) and
      24-month-old group (n = 5). Histopathological changes of the liver were observed
      after HE and Masson staining. The messenger RNA (mRNA) levels of TIMP-1, MMP-2
      and MMP-9 were determined by semi-quantitative reverse transcriptional polymerase
      chain reaction; protein expression was measured by Western blot in the livers of
      normal and transgenic mice of various ages. Changes in levels of superoxide
      dismutase (SOD), monoamine oxidase (MAO), malondialdehyde (MDA) as well as
      oxidative and anti-oxidative ability were measured. RESULTS: Histologically, more
      fatty degeneration and collagen deposition were found in the aging livers of
      transgenic mice than in those of the normal mice as their age of months
      increased. The mRNA and protein expressions of TIMP-1 were significantly high in
      the oldest animals. The histopathological changes, mRNA and protein expressions
      of TIMP-1 increased significantly in the liver of transgenic mice as compared
      with normal mice. The expression of MMP-2 and MMP-9 showed a minor change in the
      process of aging. Liver change and collagen deposition were not observed in young
      mice, but the activity of SOD decreased (P < 0.05), and the activity of MAO (P <
      0.01) and the content of MDA increased in the liver of transgenic mice (P <
      0.01). CONCLUSIONS: The expression of TIMP-1 is significantly high in the liver
      of transgenic mouse in the process of aging, indicating that the oxidative level
      increases and the anti-oxidative ability decreases in the liver of transgenic
      mouse. TIMP-1 plays an important role in the process of liver aging.

PMID- 16584650
TI  - Oncologic outcome of CO2 laser surgery for glottic carcinoma.

PMID- 16584651
TI  - Rapid prenatal diagnosis of trisomy 21 by fluorescent quantitative multiplex
      polymerase chain reaction.

PMID- 16584652
TI  - Blockade of CD154-CD40 pathway induces interleukin-10 dependent T regulatory type
      1 like cells.

PMID- 16584653
TI  - Simple bone cysts in children treated with intracystic fibrin sealant injection.

PMID- 16584654
TI  - Thymoma associated with severe diarrhoea and anaemia.

PMID- 16584655
TI  - [Effect of social desirability on dietary intake estimated from a food
      questionnaire].
AB  - INTRODUCTION: Self-report of dietary intake could be biased by social thus
      affecting risk estimates in epidemiological studies. The objective of study was
      to assess the effect of social desirability on dietary intake from a food
      frequency questionnaire (FFQ). METHODS: A convenience sample of 483 Portuguese
      university students was recruited. Subjects were invited to complete a two-part
      self-administered questionnaire: the first part included the Marlowe-Crowne
      Social Desirability Scale (M-CSDS), a physical activity questionnaire and self
      reported height and weight; the second part, included a semi-quantitative FFQ
      validated for Portuguese adults, that should be returned after fulfillment. All
      subjects completed the first part of the questionnaire and 40.4% returned the FFQ
      fairly completed. RESULTS: In multiple regression analysis, after adjustment for
      energy and confounders, social desirability produced a significant positive
      effect in the estimates of dietary fibre, vitamin C, vitamin E, magnesium and
      potassium, in both genders. In multiple regression, after adjustment for energy
      and confounders, social desirability had a significant positive effect in the
      estimates of vegetable consumption, for both genders, and a negative effect in
      white bread and beer, for women. CONCLUSION: Social desirability affected
      nutritional and food intake estimated from a food frequency questionnaire.

PMID- 16584656
TI  - Powered Endoscopic Nasal Septal Surgery.
AB  - While nasal endoscopy is typically used for diagnosis and sinus surgery,
      endoscopy can be combined with powered instrumentation to perform nasal septal
      surgery. Powered Endoscopic Nasal Septum Surgery (PENSS) is an easy, effective
      and quick alternative to traditional headlight approaches to septoplasty. PENSS
      limits the dissection to the area of the deviation and markedly reduces the
      extent of subperichondrial dissection. This is particularly valuable in patients
      who have undergone prior septal cartilage resection. PENSS was used in 2,730
      patients over 8 years. Surgical indications and technique are discussed. These
      patients had either isolated nasal septal deformities associated with other
      rhinologic pathology (sinusitis, adenoid hypertrophy polyps and external nasal
      deformity). PENSS was utilized with video assistance to allow an enhanced view of
      the endoscopic operative field. These patients were operated upon in an
      outpatient surgical suite and were seen for a post-operative video endoscopic
      evaluation at 5, 10, 15 and 20 days after surgery. The patients who had
      associated functional endoscopic sinus surgery were evaluated as needed until 6
      weeks after surgery. There were no delayed complications. Endoscopic resection of
      septal spurs, deformities and deviations can be performed safely alone or in
      combination with endoscopic sinus surgery with minimal additional morbidity.

PMID- 16584657
TI  - [Magnesium quantification in mouse brain and cerebellum grey matter].
AB  - The magnesium content in the brain and cerebellum grey matter was determined in
      20 male mice of the wistar species with a diet poor in magnesium. Significantly
      smaller values were found in the cerebellum in comparison to the brain of the
      magnesium deprived mice.

PMID- 16584658
TI  - [Iron deficiency anemia in infants. Preliminary development results at five
      years].
AB  - INTRODUCTION: Research, mostly conducted in developing countries, have suggested
      short and long term developmental delay in children who had iron-deficiency
      anemia (IDA) in their early life. This study aims to evaluate the development of
      5-years old children who were diagnosed IDA at 9 months of age. METHODS: 27
      children with IDA diagnosed at 9 months of age and 28 non-anemic controls were
      followed-up until they were 5 years old. At 9 months of age and at 5 years of
      age, blood samples were collected for blood count, iron, transferrin and
      ferritin. Children with hemoglobin < 110 g/l and ferritin < 12 ng/ml were
      diagnosed with IDA and received iron treatment for IDA correction. C Reactive
      Protein and antibody to hepatitis A virus were also studied at 5 years of age. At
      this age, children's motor and cognitive development were accessed using
      Griffith's test. RESULTS: At 9 months of age, IDA children had [mean (SD)] 102.5
      g/ l (5.9) g/l of hemoglobin and 5.6 ng/l (3.1) ng/ml of ferritin. At 5 years of
      age all children were healthy and without anemia. One child had positive antibody
      to hepatitis A virus. The results of Griffith's test at five years--anemic/non
      anemic at 9 months of age. The mean (sd)-p: general coefficient--100.8 (6.6)/99.5
      (7.1)-0.48; locomotor 110.2 (6.9)/109.3 (6.5)-0.62; personal-social--99.1
      (11.4)/95.7(11.6)-0.28; hearing-speech--93.8 (9.1)/95.3 (13.7)-0.64; hand-eye-
      98.2 (13.2)/99.1 (14.3)-0.79; performance--97.5 (17.6)/96.9 (13.6)-0.88;
      practical reasoning--89.8 (9.1)/86.3(7.1)-0.21. CONCLUSIONS: As only one child
      had positive antibody to hepatitis A virus, the study population may be
      considered as belonging to a developed region. These results suggest that, at
      least in developed regions, infants who receive an early treatment for their mild
      IDA may not be affected in global development at the age of five.

PMID- 16584659
TI  - [Thymus surgery in a general surgery department].
AB  - AIMS: Evaluation of thymectomy cases between 1990-2003, in a General Surgery
      Department. Evaluation of the therapeutic efficacy in Miastenia Gravis patients.
      PATIENTS AND METHODS: Retrospective study based on evaluation of data from
      Servico de Cirurgia, Neurologia and Consult de Neurology processes, between 1990
      2003, of 15 patients submitted to total thymectomy. RESULTS: 15 patients, aged 17
      to 72, 11 female and 4 male. Miastenia Gravis was the main indication for
      surgery, for uncontrollable symptoms or suspicion of thymoma. In patients with
      myasthenia, surgery was accomplish after compensation of symptoms. There weren't
      post-surgery complications. Pathology were divided in thymic hyperplasia and
      thymoma. Miastenia patients have there symptoms diminished or stable with
      reduction or cessation of medical therapy. CONCLUSIONS: Miastenia was the most
      frequent indication for thymectomy. Surgery was good results, with low
      morbimortality, as long as the protocols are respected.

PMID- 16584660
TI  - [Rhabdomyolysis].
AB  - Rhabdomyolysis is a common entity that often has a multifactorial etiology. It
      usually affects healthy individuals, following trauma, excessive physical
      activity, convulsive crisis, alcohol and other drugs consumption or infections.
      Accumulation of intracellular calcium, activation of proteases and lipases,
      production of free radicals and the infiltration by inflammatory cells, are some
      of the mechanisms responsible for muscular necrosis. Myoglobinuric acute renal
      failure (ARF) is only possible in the presence of myoglobin, liberated by the
      muscle cells, and of hypovolemia/renal hypoperfusion. One of the most important
      complications of this entity is electrolyte disturbance (hyperkalemia,
      hypocalcemia, metabolic acidosis), that can be aggravated by the establishment of
      ARF. The diagnosis of rhabdomyolysis relies on the elevation of creatine kinase
      and on the presence of myoglobinuria. The main therapeutic goals are removal of
      precipitating factors, handling of biochemical complications, prevention and
      treatment of ARF using renal replacement techniques when necessary. Early
      diagnosis and treatment are of critical importance in epidemic forms of
      rhabdomyolysis (e. g. earthquakes) often associated with ARF. In this setting,
      the quick access to the dialysis equipment and human resources can be compromised
      and conservative measures, as an early and vigorous hydratation associated with a
      forced alkaline diuresis, can improve the prognosis of this complication.

PMID- 16584661
TI  - [HLA-B27 polymorphism and spondyloarthropathies].
AB  - The association of HLA-B27 with ankylosing spondylitis (AS), and other
      spondyloarthropathies (SpA), remains as one of the strongest between HLA
      molecules and human disease. Since it was reported, in 1973, it has been
      extensively studied in order to understand the underlying pathogenic mechanism.
      The objective of this article is to review the current knowledge on the structure
      and polymorphism of HLA-B27 molecule, as well as describe the main pathogenic
      hypotheses trying to explain its association with AS.

PMID- 16584662
TI  - [Late traumatic diaphragmatic hernia complicated by intrathoracic perforation and
      haemorrhagic gastric cyst: a rare combination].
AB  - The authors describe the clinical and imagiologic challenges faced at the
      Emergency Room while observing a 48-year-old woman, submitted to a Nissen
      fundoplication 16 months earlier. She presented herself with a one-month total
      progressive dysphagia, epigastric pain and regurgitation. Intraoperative findings
      demonstrated an intraabdominal fundoplication, closure of diaphragmatic crura and
      part of the gastric greater curvature and body herniated through a small
      posterior defect on the diaphragm, with a gigantic serosal cystic mass and
      associated perforation. Data from posterior clinical investigation shows a
      traffic accident 34 years ago. Although described before, the association of late
      traumatic diaphragmatic hernia and gastric intrathoracic perforation is rare (<
      2.5%) and difficult to diagnose. A revision of the literature is performed
      concerning the pathophysiologic mechanisms of late diaphragmatic rupture, its
      clinical presentation and diagnosis, as for Nissen fundoplication complications,
      its prevention and management.

PMID- 16584663
TI  - [Pleuroamniotic shunting--case report].
AB  - Fetal hydrothorax refers to a collection of fluid within the fetal thorax that
      may be the result of chylous leak from the thoracic duct (primary hydrothorax) or
      generalized fluid retention associated with immune or no immune fetal hydrops
      (secondary hydrothorax). The authors' presents a case report occurred in 2002, of
      a pregnant woman that at 25 weeks' gestation that was referred to Maternidade
      Bissaya-Barreto-Coimbra because of a fetal hydrothorax at left, under tension and
      with cardiac decompensation signs. A fetal thoracocentesis was performed and the
      diagnosis was chylothorax. Because of a rapid reaccumulation of fluid a
      pleuroamniotic shunt was placed. The effusion and the cardiac decompensation
      signs regressed. The delivery was at 38 weeks' gestation. The newborn had been
      stable. Actually he has 10 months, is healthy and has a normal grow and
      development.

PMID- 16584667
TI  - [Dendritic cell vaccination--a new therapeutic alternative for cancer patients?].

PMID- 16584664
TI  - [Pituitary macroadenoma associated with pulmonary and cutaneous sarcoidosis--a
      clinical case].
AB  - Sarcoidosis is a granulomatous disease of unknown etiology that can affect all
      organs and systems, including the central nervous system in approximately 5% of
      patients. Although the hypothalamo-hypophyseal system may be one of the areas
      affected by neurosarcoidosis, pseudotumoral lesions are very rare. This paper
      reports the case of a 42-year-old male Caucasian patient followed by the
      Pneumology and Dermatology services for pulmonary and cutaneous sarcoidosis.
      Corticotherapy was initiated five months from diagnosis and the patient showed
      clear clinical and imagiological signs of improvement. In the following two
      months, the patient experienced visual disturbances and a slight decrease in
      libido, but denied having other symptoms associated with hypothalamo-hypophyseal
      hypofunction. Laboratorial evaluation (basal determinations and stimulation
      tests) revealed panhypopituitarism. The EC-NMR showed a bulky intrasellar lesion
      extending into the suprasellar and right parasellar regions, with evidence of
      optic chiasm compression, erosion of the floor of the sella and cavernous sinus
      invasion. Campimetry showed a bitemporal hemianopsia. For the purposes of
      chiasmatic decompression and histological study of the lesion the patient
      underwent a right frontal craniotomy, with a subtotal resection of the
      hypophyseal lesion. The histological diagnosis revealed a pituitary adenoma with
      no immunohistochemical expression. The patient began radiotherapy six months
      after surgery. Although today's diagnostic tools allow for a high degree of
      accuracy, hypophyseal lesions still present problems to the endocrinologist as
      their identification is essential for determining the appropriate treatment. At
      times the final diagnosis is only achieved after a histological identification of
      the lesion (biopsy/surgery). It should be noted that the described cases of
      association between sarcoidosis and hypophyseal adenoma are very rare, making the
      differential diagnosis with neurosarcoidosis difficult--a condition which has a
      preferential medical approach and a different prognosis.

PMID- 16584668
TI  - [Dendrite cell-based cancer vaccines--clinical application].
AB  - Dendritic cell (DC)-based vaccination against cancer is a specific immunotherapy
      with a new therapeutic approach for patients with cancer. Preclinical and
      clinical trials, in which more than 1,000 cancer patients received dendritic cell
      vaccination, have shown that it is possible to activate the immune system against
      cancer cells and to induce a clinical response in some of the patients. The
      treatment is so far experimental, and there is a need for well-designed trials
      that aim to improve the DC vaccine approach.

PMID- 16584669
TI  - [Dendritic cell-based cancer vaccine].
AB  - The varieties of treatments for patients with cancer have increased rapidly
      during the last few years. One of the newer ways to treat cancer patients is by
      immune therapy using tumor antigen pulsed dendritic cell-based vaccination. Phase
      I and II trials have shown effectiveness in generating an immunologic response
      and have in some cases shown clinical responses with tumour regression. This
      paper describes some of the possibilities and perspectives for dendritic cell
      vaccines for cancer patients.

PMID- 16584670
TI  - [Treatment of infantile spasms].
AB  - Infantile spasms (IS) are characterised by neurodevelopmental regression, a
      unique type of seizures and a hypsarrhythmic EEG pattern. Studies recommend the
      medical treatment of IS as a positive short-term outcome with respect to the
      spasms and in the resolution of the hypsarrhythmia. However, the data are
      insufficient to recommend medical treatment with respect to improving the long
      term outcome. The adrenocorticotropic hormone and prednisolone are recommended
      for treatment of IS, although side effects are common. Vigabatrin is also
      recommended; IS caused by tuberous sclerosis seems to respond especially well.

PMID- 16584671
TI  - [Comparison of prophylactic infusion of ephedrine and phenylephrine during
      Cesarean section under spinal anaesthesia].
AB  - Spinal anaesthesia for caesarean delivery may be associated with hypotension and
      fetal acidosis. Prophylactic infusion of phenylephrine (PE) immediately after the
      induction of anaesthesia appears to be a more effective approach than
      administration of ephedrine to reduce the incidence, frequency and severity of
      hypotension. Furthermore, PE appears to be associated with better fetal acid-base
      status than is ephedrine.

PMID- 16584672
TI  - [Profile of a systematic search. Search areas, databases and reports].
AB  - Systematic literature search is a fundamental in evidence-based medicine. But
      systematic literature search is not yet a very well used way of retrieving
      evidence-based information. This article profiles a systematic literature search
      for evidence-based literature. It goes through the most central databases and
      gives an example of how to document the literature search. The article also sums
      up the literature search in all reviews in Ugeskrift for Laeger in the year 2004.

PMID- 16584673
TI  - [Quality improvement of referrals from practising physicians. An example of a
      practicable strategy].
AB  - INTRODUCTION: Referrals from practising physicians to hospital departments are of
      varying quality. This increases the risk of inappropriate or even incorrect
      patient treatment courses. We examined the quality of referrals to a large
      department of nuclear medicine before and after initiatives aimed at improving
      the information and feedback to the practising physicians. MATERIALS AND METHODS:
      An evaluation of the quality of referrals (n = 579) from praticising physicians
      to the Department of Nuclear Medicine, Odense University Hospital, Denmark,
      recorded during two periods of three months each before and after (1) publication
      of a referral guideline and (2) a feedback response to those physicians whose
      referrals were insufficient. A general practitioner (GP) and a specialist in
      nuclear medicine (NM) judged independently whether the referrals were good,
      acceptable or unacceptable. RESULTS: During the two periods, 281 and 298
      referrals were received, respectively. Of these, 37% and 27%, respectively, were
      from practising specialists (PSs). After intervention, 23% more referrals were
      received from GPs, and the share of "good" referrals also increased
      (before/after: 48%/72% (GP), 61%/84% (NM)). In contrast, there was a 23% decrease
      in referrals from PSs, whereas the share of "good" referrals remained unchanged
      or increased (before/after: 64%/66 % (GP), 64%/96% (NM)). In addition, there was
      a change in the referral pattern from both GPs and PSs. CONCLUSION: Relatively
      simple and inexpensive intervention caused an increase in the number and quality
      of referrals from GPs and a fall in referrals from PSs without an obvious
      improvement in quality.

PMID- 16584674
TI  - [Quality control of whole-body bone scintigraphy. Patient surveys].
AB  - INTRODUCTION: The quality of health care is but sparsely elucidated; surveys of
      complete patient courses hardly exist. We established and used benchmarks for a
      major nuclear medicine examination: whole-body bone scintigraphy. MATERIALS AND
      METHODS: The study material included 458 out of 512 consecutive examinations.
      Patients were referred by general practitioners (12%), practising specialists
      (16%) and hospital departments (72%). The survey dealt with waiting times and
      information provided, as judged by the patient, the referring physician and the
      Department of Nuclear Medicine (DNM) in relation to referrals, reporting and the
      passing on of the results to the patient. The DNM judged the quality of the
      examinations, and the referring physician assessed the implications for diagnosis
      and treatment. RESULTS: In 10% of the cases, the patient felt that the waiting
      time was unsatisfactory, as the referring physician might take up to 150 days to
      send the referral and because 11% had, after two months, still not been informed
      of the examination result. Supplementary tomography was used in 38 examinations
      (8%); of these, only one (3%) provided new evidence. Based on the examination
      results, the referring physician could make a diagnosis and/or wanted to change
      management for 61% of patients. CONCLUSION: Referrals were delayed mainly by the
      referring physicians, who often forgot to inform their patients of the
      examination results. Special admissions seldom yielded extra information. The
      examination result had important clinical implications in almost two thirds of
      patients.

PMID- 16584675
TI  - [General practitioners' attitudes towards the diagnosis of lung cancer and the
      diagnostic organisation].
AB  - INTRODUCTION: The aim of this study was to determine whether there is a
      nihilistic attitude towards diagnosing lung cancer among Danish general
      practitioners (GPs) and to obtain the GPs' evaluation of the present approach to
      lung cancer diagnosis. MATERIALS AND METHODS: A questionnaire was sent to 1,186
      randomly selected GPs. Most of the questions addressed the possibilities of
      improving primary prevention, GPs' attitudes towards diagnosing lung cancer,
      their opinions about waiting times and their clinical practice. RESULTS: A total
      of 848 (71%) completed the questionnaire. Only 12% agreed with the statement that
      the prognosis for lung cancer is so unfavourable that there is no hurry to
      diagnose the disease, while 22% agreed to the statement that diagnostic delay
      rarely means anything for the prognosis. About half of the GPs found the
      diagnostic period too long. There were, however, wide variations among the
      different counties in Denmark. The majority of GPs followed the recommendations
      of the Danish Lung Cancer Group for diagnosing lung cancer, especially the
      elderly GPs, who were also more inclined to make follow-up appointments after
      lung infections. More than one in every four practitioners was reluctant to use
      the word "cancer" in referrals to hospitals or for investigation. CONCLUSION: The
      study showed that Danish GPs do not have a nihilistic attitude towards diagnosing
      lung cancer and that elderly practitioners are more careful about diagnosing lung
      cancer. GPs' satisfaction with waiting times varies widely among the different
      counties in Denmark. Many practitioners were reluctant to use the word "cancer"
      in referrals.

PMID- 16584676
TI  - [HCG in the treatment of cryptorchidism. The effect of age and position of the
      testis].
AB  - In a recent study, the effect of human chorionic gonadotropin (HCG) in the
      treatment of children with cryptorchidism aged less than four years was
      questioned. The purpose of the present study was to determine, on the basis of a
      retrospective examination of patients' records, the effect of HCG treatment,
      whether outcomes are age-dependent and whether the effects of treatment are
      related to the position of the testis. Patients diagnosed with undescended testis
      who had been treated at the Department of Urology at Gentofte Hospital
      (Copenhagen) in the period from 1 November 1998 to 31 May 2003 were identified.
      Patients who had been treated with HCG were included in the sample. Boys who at
      an earlier stage had been operated on in the inguinal or scrotal region, or who
      had suffered from inguinal hernia, were excluded, and clinical retractile testes
      were separated from true undescended testes. The criterion of success for
      efficient treatment was complete descent to the bottom of the scrotum. In the 306
      records examined, 121 patients met the inclusion criteria. In total, there were
      170 undescended testes. The patients' median age at time of treatment was 3.6
      years. The overall success rate was 34.7%. The success rates in the individual
      age categories were: 1-2 years, 36.7%; 3-4 years, 33.4%; and 5-13 years, 35%. The
      position of the testis at the beginning of treatment showed that the lower the
      pretreatment position, the better the success rate. The overall success of HCG
      treatment of cryptorchidism was 34.7%. No age dependency of HCG effects was
      found, but the position of the testis before treatment influenced the success
      rate.

PMID- 16584677
TI  - [Reduced vision in Wernicke's syndrome with symptoms of nystagmus].
AB  - A 42-year-old man presented in the Department of Ophthalmology of Holstebro
      Central Hospital with a history of alcohol abuse, vomiting and weight loss. The
      initial symptoms of beriberi were stiffness of the legs and a picture of
      Wernicke's syndrome. He had bilateral loss of horizontal eccentric gaze holding
      and upbeat nystagmus, and visual acuity was reduced to counting fingers. Visual
      acuity was tested in the down-gaze position and increased to 0.3 because of
      reduced nystagmus. The patient's oculomotor function improved dramatically after
      treatment with thiamine. Wernicke's encephalopathy and beriberi are discussed,
      highlighting that nystagmus may be the single ocular symptom. It should be
      considered in the differential diagnosis of bilateral ophthalmoplegia even in the
      absence of altered mental status.

PMID- 16584678
TI  - [Endovascular embolisation of severe bleeding in connection with periacetabular
      osteotomy].
AB  - Embolisation is a well-known procedure for trauma patients with pelvic injuries
      and bleeding complications. We report a case in which haemostasis was
      successfully achieved by angiographic embolisation in a patient with bleeding
      complications due to periacetabular osteotomy. This case illustrates that the
      technique is an alternative to vascular surgery when bleeding complications occur
      during surgery.

PMID- 16584691
TI  - [Peripheral cholangiocarcinoma: results of surgical treatment].
AB  - INTRODUCTION: Peripheral cholangiocarcinoma (PC) is an uncommon primary hepatic
      tumor that represents 10% of hepatic resections for primary malignant tumors in
      our experience. PATIENTS AND METHODS: From 1988 to 2004, 29 patients with a
      diagnosis of PC were treated in our unit. One patient was treated with
      chemoembolization and the remainder underwent surgery. In 7 patients, hepatectomy
      was not performed due to the presence of an extrahepatic tumor or massive hepatic
      invasion. The resectability index was 75%. Twenty-one patients underwent radical
      excision of PC and comprised the study group. RESULTS: The mean age was 60 years
      with a slight predominance of women. Sixty-two patients were symptomatic and
      tumoral markers were elevated in 58%. PC developed in normal liver in 15
      patients, in cirrhotic liver in 2 patients and in the context of chronic
      hepatitis in 4 patients. The mean tumoral size was 7 cm (between 1.6 and 13 cm).
      Multiple tumors were found in 3 patients, invasion of the hepatic hilum lymph
      nodes was found in 8 patients and vascular invasion was observed in a further 8
      patients. Major hepatectomy was performed in 90% of the patients; radical
      lymphadenectomy of the hepatic hilum was performed in 15 patients and excision of
      the extrahepatic biliary tract followed by Roux-en-Y hepaticojejunostomy in 4
      patients. Operative mortality occurred in 3 patients (14%); one cirrhotic patient
      died 4 days after surgery from cardiovascular causes and 2 patients died from
      liver failure after extensive hepatectomies that included resection of the
      inferior vena cava and suprahepatic veins. Complications occurred in 33% of the
      patients. Ten patients (47%) died. Of these, 6 died from tumoral recurrence.
      Tumoral recurrence occurred in 9 patients (5 hepatic and 4 extrahepatic). Hepatic
      recurrences were treated with radiofrequency ablation in 2 patients and
      chemotherapy in 5 patients. The median survival was 11 months. Actuarial survival
      at 1, 3 and 5 years was 60%, 47% and 47% respectively. Disease-free survival at
      1, 3 and 5 years was 50%, 31% and 31% respectively. In univariate analysis,
      significant risk factors for mortality were lymphatic invasion and a resection
      margin of less than 1 cm. In multivariate analysis, negative factors for tumoral
      recurrence were lymphatic invasion, satellitosis, and poor tumoral delimitation.
      CONCLUSION: Surgical treatment of PC through radical hepatic resection with
      margins of more than 1 cm in patients without nodal invasion provides good
      results with a 5-year survival of 79%.

PMID- 16584692
TI  - [Microsomal oxidative metabolism in the liver of rats treated with vinorelbine:
      evaluation through antipyrine elimination].
AB  - BACKGROUND: Determination of the metabolic efficiency of the liver in neoplastic
      diseases in patients receiving highly toxic drugs is of great practical
      importance. METHODS: The effect of vinorelbine on the metabolic efficiency of the
      liver was evaluated by means of phenazone kinetics in rats. The test was compared
      with a battery of tests routinely used whenever hepatic dysfunction is suspected.
      RESULTS: Vinorelbine was administered to the rats and the pharmacokinetic
      parameters of antipyrine were compared with those in control rats. A
      statistically significant prolongation of the elimination half-life, as well as a
      decrease in the elimination constant and clearance of antipyrine were found in
      the rats receiving the anticancer drug in comparison with controls (p < 0.01).
      Statistically significant correlations were found between the elimination half
      life of antipyrine and serum albumin values (p < 0.01) and prothrombin time (p <
      0.001). CONCLUSIONS: Determination of antipyrine pharmacokinetics allows early
      detection of vinorelbine-induced hepatic dysfunction, with a sensitive scale.

PMID- 16584693
TI  - [Utility of bolus somatostatin administration in preventing pancreatitis after
      endoscopic retrograde cholangiopancreatography: a controlled, non-randomized
      study].
AB  - INTRODUCTION: Somatostatin is one of the most extensively evaluated drugs in the
      prophylaxis of pancreatitis after endoscopic retrograde cholangiopancreatography
      (ERCP), but its utility remains controversial. PATIENTS AND METHODS: The aim of
      this study was to evaluate the role of somatostatin as prophylaxis of ERCP
      induced acute pancreatitis. A group of consecutive patients that underwent ERCP
      in our endoscopy unit was prospectively studied for 8 months. Patients in this
      group were administered an endovenous bolus of 250 micrograms of somatostatin
      immediately before introducing the catheter in the papilla of Vater (somatostatin
      group). This group was compared with another group composed of consecutive
      patients who had undergone ERCP in the 8 previous months, without somatostatin
      administration (placebo group). Both groups contained the same number of
      patients. The following variables were recorded; sex, age, contrast injection in
      the duct of Wirsung, endoscopist, therapeutic maneuvers, and the development of
      post-ERCP pancreatitis. RESULTS: During the 16 months of patient inclusion, we
      performed 320 ERCP in our unit, of which 248 were included in the study: 142 in
      the somatostatin group and 142 in the placebo group. Of these patients, 152
      (53.5%) were men and 132 (46.5%) were women. The mean age was 70.05 +/- 13.83
      years (range: 27-93 years). Acute pancreatitis occurred in 10 patients in the
      somatostatin group and in 5 in the placebo group; this difference was not
      statistically significant (p > 0.05). No significant differences were found
      between the two groups in the remaining variables studied. CONCLUSION:
      Somatostatin does not seem to be useful in preventing post-ERCP acute
      pancreatitis.

PMID- 16584695
TI  - [Idiopathic cholestasis associated with bloody diarrhea as the first
      manifestation of Hodgkin's lymphoma].
AB  - Jaundice in Hodgkin's disease occurs in 3-13% of the cases reported in the
      medical literature and can be due to several causes. Cholestatic jaundice
      associated with ductopenia may be a consequence of an associated paraneoplastic
      process and can occur several months before the development of Hodgkin's disease.
      When there is a finding of jaundice of unknown etiology associated with
      ductopenia, the possible existence of Hodgkin's disease should be investigated.
      We describe a case of cholestatic jaundice associated with Hodgkin's disease. The
      first clinical and laboratory manifestations were symptoms of bloody diarrhea
      months before the development of Hodgkin's disease. We discuss the differential
      diagnoses considered, given the complexity of the case.

PMID- 16584694
TI  - [Symptomatic hepatic arterioportal shunt resolved through conservative
      treatment].
AB  - Arterioportal shunt in the liver is a rare vascular disorder that may be due to
      congenital vascular malformation (hereditary hemorrhagic telangiectasia), trauma,
      iatrogenic causes (after a hepatic biopsy) or neoplasm. Initial treatment
      consists of transcatheter arterial embolization with different kinds of
      materials. We present the case of a 64-year-old woman with signs of portal
      hypertension and severe diarrhea. Doppler ultrasonography, computed tomography
      and angiography revealed arterioportal fistulae between the hepatic artery and
      right portal vein. Transcatheter arterial embolization with n-butyl-2
      cyanoacrylate surgical glue (Glubran) was successfully performed. After 2 years
      of follow-up, the patient remains asymptomatic. Transcatheter arterial
      embolization with Glubran should be considered as a therapeutic option in
      arterioportal shunts and could be a definitive therapy.

PMID- 16584696
TI  - [Epidemiology and natural history of primary nonalcoholic fatty liver disease].
AB  - The clinical impact of nonalcoholic fatty liver disease depends on its prevalence
      and natural history. The prevalence in the adult population is estimated to be
      about 23% and is on the increase. Thus, it has become the most common cause of
      persistent elevated liver enzymes, chronic liver disease, and cryptogenic
      cirrhosis in developed countries. The increasing prevalence of nonalcoholic fatty
      liver disease, which is approaching epidemic proportions, is parallel to that of
      other disorders associated with insulin resistance, especially obesity and type 2
      diabetes mellitus. This entity occurs in men and women equally and in all age
      groups. The natural history is poorly defined mainly due to the scarcity of
      histologic follow-up studies. Although steatosis alone has a more benign clinical
      course, steatohepatitis is a progressive fibrotic disease, in which cirrhosis and
      liver-related death occur in a similar way to other causes of chronic liver
      diseases. Progression seems to be mainly dependent on the severity of
      histological damage at diagnosis, but age older than 40 years, obesity, and type
      2 diabetes have also been associated with an increased risk of liver fibrosis and
      progression to cirrhosis.

PMID- 16584697
TI  - [Clinical research techniques in functional digestive disorders].
AB  - Functional digestive disorders are characterized by symptoms related to the
      digestive tract for which no pathological causes can be found using routine
      diagnostic techniques. In the last few years, several methods have been developed
      to the study digestive function allow relation between in humans functional
      alterations, mainly motor and sensory and to be related to functional digestive
      symptoms. As a result of these advances, both motor and sensory alterations have
      been identified in subgroups of patients with functional digestive disorders.
      This knowledge should enable current symptom-based classifications of these
      disorders to be replaced with new classifications based on specific
      physiopathologic mechanisms. This would allow more effective therapies aimed at
      the specific mechanism causing the symptoms to be developed.

PMID- 16584698
TI  - Cardiovascular abnormalities in special conditions of advanced cirrhosis. The
      circulatory adaptative changes to specific therapeutic procedures for the
      management of refractory ascites.
AB  - Advanced liver disease is characterized by decreased arterial blood pressure and
      peripheral vascular resistances, increased cardiac output and heart rate in the
      setting of a hyperdynamic circulatory pattern favoured by total blood volume
      expansion, circulatory overload and overactivity of the endogenous vasoactive
      systems. Reduced heart responses to stressful conditions such as changes in
      loading conditions of the heart in presence of further deterioration of liver
      function such as refractory ascites, hepatorenal syndrome, spontaneous bacterial
      peritonitis and bleeding esophageal varices have been recently identified and the
      knowledge of the cirrhotic cardiomyopathy syndrome has gained the dignity of a
      new clinical entity. Facing the availability of therapeutic interventions
      (paracentesis, transjugular intrahepatic portosystemic shunt, peritoneovenous
      shunt, orthotopic liver transplantation) currently employed to manage the life
      threatening complications of the most advanced phases of cirrhotic disease, the
      knowledge of their impact on cardiovascular function is of paramount relevance.

PMID- 16584699
TI  - [Peritoneal pseudomyxoma. Utility of intraperitoneal chemohyperthermia after
      surgery].

PMID- 16584700
TI  - [Pancreaticobronchial fistula as the first manifestation of pancreatic
      pseudocysts].

PMID- 16584701
TI  - [Hemostatic clip-assisted placement of enteral feeding tubes].

PMID- 16584702
TI  - The impact of secondary task cognitive processing demand on driving performance.
AB  - Crash causation research has identified inattention as a major source of driver
      error leading to crashes. The series of experiments presented herein investigate
      the characteristics of an in-vehicle information system (IVIS) task that could
      hinder driving performance due to uncertainty buildup and cognitive capture.
      Three on-road studies were performed that used instrumented passenger and tractor
      trailer vehicles to obtain real-world driving performance data. Participants
      included young, middle-aged, and older passenger vehicle drivers and middle-aged
      and older commercial vehicle operators. While driving, they were presented with
      IVIS tasks with various information densities, decision-making elements,
      presentation formats, and presentation modalities (visual or auditory). The
      experiments showed that, for both presentation modalities, the presence of
      multiple decision-making elements in a task had a substantial negative impact on
      driving performance of both automobile drivers and truck drivers when compared to
      conventional tasks or tasks with only one decision-making element. The results
      from these experiments can be used to improve IVIS designs, allowing for
      potential IVIS task phenomena such as uncertainty buildup and cognitive capture
      to be avoided.

PMID- 16584703
TI  - Is there any evidence for noncoached pushing in women with epidurals?

PMID- 16584704
TI  - Synchronous fluorescence, UV-visible spectrophotometric, and voltammetric studies
      of the competitive interaction of bis(1,10-phenanthroline)copper(II) complex and
      neutral red with DNA.
AB  - Constant wavelength synchronous fluorescence spectroscopy (CW-SFS), UV-visible
      absorption spectroscopy, and cyclic and differential pulse voltammetry were
      applied to investigate the competitive interaction of DNA with the bis(1,10
      phenanthroline)copper(II) complex cation ([Cu(phen)(2)](2+)) and a fluorescence
      probe, neutral red dye (NR), in a tris-hydrogen chloride buffer (pH 7.4). The
      results show that both the [Cu(phen)(2)](2+)and the NR molecules can intercalate
      competitively into the DNA double-helix structure. The cyclic voltammetry method
      showed that both anodic and cathodic currents of [Cu(phen)(2)](2+) decreased on
      addition of the DNA and the intercalated [Cu(phen)(2)](2+)-DNA complex formed
      (beta = (4.14 +/- 0.24) x 10(3)). CW-SFS measurements were facilitated by the use
      of the three-way resolution of the CW-SFS for NR, [Cu(phen)(2)](2+), and NR-DNA.
      The important constant wavelength (CW) interval, Deltalambda, was shown to vary
      considerably when optimized (135, 58, and 98 nm for NR, NR-DNA, and
      [Cu(phen)(2)](2+), respectively). This approach clearly avoided the errors that
      otherwise would have arisen from the common assumption that Deltalambda is
      constant. Furthermore, a chemometrics approach, parallel factor analysis
      (PARAFAC), was applied to resolve the measured three-way CW-SFS data, and the
      results provided simultaneously the concentration information for the three
      reaction components, NR, [Cu(phen)(2)](2+), and NR-DNA, for the system at each
      equilibrium point. The PARAFAC analysis indicated that the intercalation of the
      [Cu(phen)(2)](2+) molecule into the DNA proceeds by exchanging with the NR probe
      and can be attributed to two parallel reactions. Comprehensive information was
      readily obtained; the replacement of the intercalated NR commenced immediately on
      introduction of [Cu(phen)(2)](2+), approximately 50% of NR was replaced by
      [Cu(phen)(2)](2+) at a concentration of 0.45 x 10(-5) mol L(-1), and nearly all
      of the NR was replaced at a [Cu(phen)(2)](2+) concentration of 2.50 x 10(-5) mol
      L(-1). This work has the potential to improve extraction of information from the
      fluorescence intercalator displacement (FID) assay.

PMID- 16584705
TI  - Protein kinase D directly phosphorylates histone deacetylase 5 via a random
      sequential kinetic mechanism.
AB  - Class II histone deacetylases (HDACs) are signal-responsive repressors of gene
      transcription. In the heart, class II HDAC5 suppresses expression of genes that
      govern stress-induced cardiomyocyte growth. Signaling via pro-growth G protein
      coupled receptors triggers phosphorylation of HDAC5 on two serine residues
      (Ser(259) and Ser(498)), resulting in nuclear export of HDAC5 and de-repression
      downstream target genes. Although prior studies established a role for protein
      kinase D (PKD) in the regulation of HDAC5 phosphorylation, it remained unclear
      whether PKD functions directly or indirectly to control the phosphorylation
      status of this transcriptional repressor. Here, we demonstrate that PKD catalyzes
      direct phosphoryl-group transfer to Ser(498) of HDAC5. Each of the three PKD
      family members, PKD1, PKD2, and PKD3, is capable of phosphorylating HDAC5 (K(m)
      for substrate=2.07, 3.12, and 1.43microM, respectively), although PKD2 exhibits
      highest catalytic efficiency (k(cat)/K(m)=6.77min(-1)microM(-1)). Kinetic studies
      revealed that the three PKD isozymes phosphorylate HDAC5 through a random
      sequential mechanism, and that ATP has no effect on association of kinase with
      peptide substrate. In addition, we demonstrate that ADP competitively inhibits
      phosphorylation of HDAC5 (K(i)=8.50, 17.54, and 11.98microM for PKD1, PKD2, and
      PKD3, respectively). These findings define PKD as an HDAC kinase and thus suggest
      key roles for PKD family members in the control of chromatin structure and gene
      expression.

PMID- 16584706
TI  - Sleep bruxism and temporomandibular disorder: Clinical and polysomnographic
      evaluation.
AB  - OBJECTIVE: To seek better understanding of chronic musculoskeletal facial pain
      and its relation to sleep bruxism, by comparing patients with sleep bruxism, with
      and without temporomandibular disorder. DESIGN: Forty sleep bruxism patients were
      evaluated according to the Research Diagnostic Criteria for Temporomandibular
      Disorders: group A-20 patients with myofascial pain, 3 men, 17 women; average age
      32.7yr; mean duration of pain 4.37yr; group B-20 without myofascial pain, 5 men,
      15 women; average age 30.8yr. Sleep and bruxism were evaluated in one-night
      polysomnography. RESULTS: There were no statistically significant differences for
      bruxism and sleep variables of the two groups: number of bursts and bruxism
      episodes per hour, amplitude and duration of bruxism episodes, sleep efficiency
      and latency, percentage of non-REM and REM sleep, respiratory events, periodic
      limb movements, and micro-arousals. CONCLUSIONS: The polysomnographic
      characteristics of patients with sleep bruxism, with and without orofacial pain,
      are similar. More studies are necessary to clarify the reasons why some sleep
      bruxism patients develop chronic myofascial pain, and others do not.

PMID- 16584707
TI  - S-nitrosothiol inhibition of mitochondrial complex I causes a reversible increase
      in mitochondrial hydrogen peroxide production.
AB  - We found that reversible inactivation of mitochondrial complex I by S-nitroso-N
      acetyl-D,L-penicillamine (SNAP) in isolated rat heart mitochondria resulted in a
      three-fold increase in H2O2 production, when mitochondria were respiring on
      pyruvate and malate, (but not when respiring on succinate or in the absence of
      added respiratory substrate). The inactivation of complex I and the increased
      H2O2 production were present in mitochondria washed free of SNAP or NO, but were
      partially reversed by light or dithiothreitol, treatments known to reverse S
      nitrosation. Specific inhibition of complex I with rotenone increased H2O2
      production to a similar extent as that caused by SNAP. The results suggest that S
      nitrosation of complex I can reversibly increase oxidant production by
      mitochondria, which is potentially important in cell signalling and/or pathology.

PMID- 16584708
TI  - In situ characterization of lipid A interaction with antimicrobial peptides using
      surface X-ray scattering.
AB  - Lipid A structure at the air-aqueous interface has been studied using pressure
      area isotherm methods coupled with the surface X-ray scattering techniques of X
      ray reflectivity (XR) and grazing incidence X-ray diffraction (GIXD). Lipid A
      monolayers were formed at the air-aqueous interface to represent the lipid moiety
      of the outer membrane of Gram-negative bacteria. Lipid A structure was
      characterized at surface pressures between 10 and 35 mN/m. Interactions of alpha
      helical antimicrobial peptides LL-37, SMAP-29 and D2A22 with lipid A monolayers
      were subsequently studied. Although insertion into the lipid A monolayers was
      observed with the alpha-helical peptides, little change was seen from the X-ray
      data, suggesting that the lipid A hydrocarbon chains are involved in
      reorientation during insertion and that the hydrocarbon chains have a relatively
      rigid structure.

PMID- 16584709
TI  - Is photobleaching necessary for Raman imaging of bone tissue using a green laser?
AB  - Raman microspectroscopy is widely used for musculoskeletal tissues studies. But
      the fluorescence background obscures prominent Raman bands of mineral and matrix
      components of bone tissue. A 532-nm laser irradiation has been used efficiently
      to remove the fluorescence background from Raman spectra of cortical bone.
      Photochemical bleaching reduces over 80% of the fluorescence background after 2 h
      and is found to be nondestructive within 40 min. The use of electron multiplying
      couple charge detector (EMCCD) enables to acquire Raman spectra of bone tissues
      within 1-5 s range and to obtain Raman images less than in 10 min.

PMID- 16584711
TI  - Firing pattern of rat hippocampal neurons: a perforated patch clamp study.
AB  - To test whether the slow afterhyperpolarization (sAHP) underlies the filter
      function of hippocampal granule cells (GCs), we compared the sAHP and spike
      frequency adaptation between granule cells and CA3 pyramidal cells (PCs) in
      hippocampal slices employing gramicidin perforated patch clamp recordings to best
      preserve the physiological cytoplasmic constitution. sAHPs were evoked in GCs and
      PCs with trains of action potentials in current clamp mode and showed comparable
      kinetics in both types of cells. The threshold frequency (500 ms firing)
      triggering a detectable sAHP was approximately 10 Hz and approximately 3 Hz in
      GCs and PCs, respectively. Half maximal sAHPs were reached at 30 Hz and 8 Hz in
      GCs and PCs, respectively. Maximal amplitude of sAHPs in GCs amounted to
      approximately 3.5 mV, was approximately 2-fold smaller than in PCs and could not
      be further increased with higher firing frequencies. The time course of sAHP
      activation was investigated with 50 Hz trains of action potentials applied for
      increasing durations. In both types of cells, the sAHP amplitude increased with a
      time constant of approximately 400 ms. Nevertheless, sAHP never exceeded 4 mV in
      GCs but rose to approximately 12 mV in PCs when cells fired for 3 s. The
      repetitive firing pattern of GCs and PCs was compared by injecting current
      amplitudes adjusted to provoke an initial firing frequency of 50 Hz. In GCs
      firing frequency declined slower (tau = 229 ms) and leveled off at a higher tonic
      firing frequency (28 Hz) when compared to PCs (tau = 126 ms, 18 Hz). We conclude
      that the intrinsic excitability of GCs cannot be primarily regulated by the sAHP.
      The sAHP in GCs is minimal most likely due to a small sAHP-channel density as
      well as to a more rigid control of intracellular Ca(2+) levels.

PMID- 16584710
TI  - Intraocular injection of folate antagonist methotrexate induces neuronal
      differentiation of embryonic stem cells transplanted in the adult mouse retina.
AB  - Transplanted embryonic stem (ES) cells can be integrated into the retinas of
      adult mice as well-differentiated neuronal cells. However, the integrated ES
      cells also have a tumorigenic effect just because they have the ability for
      multipotential differentiation to various types of tissues. Thus, control of
      neoplastic potentials of ES cells is very important for the treatment of
      degenerative or injured diseases. Mouse ES cells carrying the sequence for the
      green fluorescent protein (GFP) gene were transplanted into adult mouse retinas
      by intravitreal injections 20 h after intravitreal N-methyl-d-aspartate (NMDA)
      administration. One week after the ES cell injection, folate antagonist
      methotrexate (MTX) was injected intravitreally. Eyes were retrieved 4 weeks after
      ES cell transplantation for histologic analyses. Conventional histological
      analysis was performed by hematoxylin and eosin staining with the use of paraffin
      embedded sections. Neuronal differentiation and teratogenic potential of ES cells
      were demonstrated by immunohistochemistry. The proliferative activity of
      transplanted cells was detected by mitotic index, proliferating cell nuclear
      antigen index and AgNOR count. The incorporation of transplanted ES cells in MTX
      treated and non-treated retinas at 4 weeks after transplantation was observed in
      8/16 eyes (50%) and 8/16 eyes (50%), respectively. Transplanted ES cells in MTX
      treated retina showed increased neuronal differentiation and decreased expression
      of teratogenic markers, compared with ES cells in non-treated retina. The
      proliferative activity of transplanted ES cells in MTX-treated retina was lower
      than that in non-treated retina. These results suggest that intravitreal MTX
      treatment following transplantation can induce neuronal differentiation in the
      transplanted ES cells and decrease their proliferative activity.

PMID- 16584712
TI  - Synthesis of N-glycan oxazolines: donors for endohexosaminidase catalysed
      glycosylation.
AB  - Oxazoline mono-, di-, tri- and hexasaccharides, corresponding to the core
      components of N-linked glycoprotein high mannose glycans, are synthesised as
      potential glycosyl donors for endohexosaminidase catalysed glycosylation of
      glycopeptides and glycoprotein remodelling. The crucial beta-D-Manp-(1-->4)-D
      GlcpNAc linkage is synthesised via epimerisation of gluco disaccharide substrates
      by sequential triflation and nucleophilic substitution. Oxazolines are formed
      directly from the anomeric OPMP protected N-acetyl glucosamine derivatives.
      Efficient endohexosaminidase catalysed glycosylation of a synthetic beta-D
      GlcpNAcAsn glycosyl amino acid is demonstrated with the trisaccharide oxazoline
      donor.

PMID- 16584713
TI  - The signal-to-noise ratio as a measure of HA oligomer concentration: a MALDI-TOF
      MS study.
AB  - MALDI-TOF MS (matrix-assisted laser desorption and ionization time-of-flight mass
      spectrometry) was used to determine ng amounts of defined hyaluronan (HA)
      oligomers obtained by enzymatic digestion of high molecular weight HA with
      testicular hyaluronate lyase. The signal-to-noise (S/N) ratio of the positive and
      negative ion spectra represents a reliable concentration measure: Amounts of HA
      down to about 40 fmol could be determined and there is a linear correlation
      between the S/N ratio and the HA amount between about 0.8 pmol and 40 fmol.
      However, the detection limits depend considerably on the size of the HA oligomer
      with larger oligomers being less sensitively detectable. The advantages and
      drawbacks of the S/N ratio as concentration measure are discussed.

PMID- 16584714
TI  - Enzymatic characterization of O-GlcNAcase isoforms using a fluorogenic GlcNAc
      substrate.
AB  - A highly sensitive fluorogenic hexosaminidase substrate, fluorescein di(N-acetyl
      beta-D-glucosaminide) (FDGlcNAc), was prepared essentially as described
      previously [Chem. Pharm. Bull. 1993, 41, 314] with some modifications. The
      fluorescent analog is a substrate for a number of hexosaminidases but here we
      have focused on the cytoplasmic O-GlcNAcase isoforms. Kinetic analysis using
      purified O-GlcNAcase and its splice variant (v-O-GlcNAcase) expressed in
      Escherichia coli suggests that FDGlcNAc is a much more efficient substrate (Km =
      84.9 microM) than the conventional substrate, para-nitrophenyl 2-acetamido-2
      deoxy-beta-D-glucopyranoside (pNP-beta-GlcNAc, Km = 1.1 mM) and a previously
      developed fluorogenic substrate, 4-methylumbelliferyl 2-acetamido-2-deoxy-beta-D
      glucopyranoside [MUGlcNAc, Km = 0.43 mM; J. Biol. Chem. 2005, 280, 25313] for O
      GlcNAcase. The variant O-GlcNAcase, a protein lacking the C-terminal third of the
      full-length O-GlcNAcase, exhibited a Km of 2.1 mM with respect to FDGlcNAc. This
      shorter isoform was not previously thought to exhibit O-GlcNAcase activity based
      on in vitro studies with pNP-beta-GlcNAc. However, both O-GlcNAcase isoforms
      reduced O-GlcNAc protein levels extracted from HeLa and HT-29 cells in vitro,
      indicating that the splice variant is a bona fide O-GlcNAcase. Fluorescein di-N
      acetyl-beta-D-galactosaminide (FDGalNAc) is not cleaved by these enzymes,
      consistent with previous findings that the O-GlcNAcase has substrate specificity
      toward O-GlcNAc but not O-GalNAc. The enzymatic activity of the shorter isoform
      of O-GlcNAcase was first detected by using highly sensitive fluorogenic FDGlcNAc
      substrate. The finding that O-GlcNAcase exists as two distinct isoforms has a
      number of important implications for the role of O-GlcNAcase in hexosamine
      signaling.

PMID- 16584715
TI  - A theoretical study of glucose mutarotation in aqueous solution.
AB  - In this work the mechanism of glucose mutarotation is investigated in aqueous
      solution considering the most likely pathways proposed from experimental work.
      Two mechanisms are studied. The first involves an intramolecular proton transfer
      as proposed by textbooks of organic chemistry, and the second uses one solvent
      water molecule to assist proton transfer. Both mechanisms are studied in the gas
      phase and in aqueous solution with the help of a polarizable continuum model,
      which is adopted to introduce the electrostatic nonspecific influence of bulk
      solvent. The structures are fully characterized through the calculation of the
      corresponding vibrational frequencies. The rate coefficients for each mechanism
      are calculated following transition-state theory in both the gas phase and in
      aqueous solution. Values computed for the water-assisted pathway in the continuum
      solvent agree best with the experimental results.

PMID- 16584716
TI  - Highly regioselective synthesis of a 3-O-sulfonated arabino Lewis(a) asparagine
      building block suitable for glycopeptide synthesis.
AB  - Using the stannylene method, the trisaccharide 2-acetamido-3-O-[6-O-benzyl-beta-D
      galactopyranosyl]-4-O-[2,3,4-tri-O-benzyl-beta-D-arabinopyranosyl]-6-O-benzyl-2
      deoxy-beta-D-glucopyranosyl azide was regioselectively sulfonated and, after
      reduction of the anomeric azide, coupled to Fmoc alpha-allyl aspartate. After
      Pd(0)-catalyzed deallylation, the sulfatyl Lewis(a) asparagine building block was
      obtained, suitable for solid-phase glycopeptide synthesis applying the fluoride
      labile PTMSEL linker system.

PMID- 16584718
TI  - Protein-mediated energy-dissipating pathways in mitochondria.
AB  - Mitochondrial production of reactive oxygen species (ROS) is a well-established
      fact of fundamental importance to aging and etiology of many pathologies with
      serious public health implications. The ROS production is an innate property of
      mitochondrial biochemistry inseparable from the oxidative metabolism. Recent
      discoveries indicate that in addition to several ROS-detoxifying enzyme systems,
      which remove ROS, mitochondria may also be able to limit their ROS production by
      the mechanism comprising several protein-mediated energy-dissipating
      ("uncoupling") pathways. Although the physiological significance and in vivo
      modus operandi of these pathways remain to be elucidated, several proteins
      potentially capable of energy dissipation are known. This mini-review addresses
      the identity of mitochondrial protein-mediated energy-dissipating pathways and
      the experimental evidence to their role in controlling ROS production.

PMID- 16584717
TI  - NIS/TFA: a general method for hydrolyzing thioglycosides.
AB  - A variety of thioglycosides are chemoselectively hydrolyzed to the corresponding
      1-hydroxy glycosides using equimolar amounts of NIS/TFA as promoter systems.

PMID- 16584720
TI  - Surface plasmon resonance in protein-membrane interactions.
AB  - Surface plasmon resonance (SPR) has become one of the most important techniques
      for studying macromolecular interactions. The most obvious advantages of SPR over
      other techniques are: direct and rapid determination of association and
      dissociation rates of binding process, no need for labelling of protein or
      lipids, and small amounts of sample used in the assay (often nM concentrations of
      proteins). In biochemistry, SPR is used mainly to study protein-protein
      interactions. On the other hand, protein-membrane interactions, although crucial
      for many cell processes, are less well studied. Recent advances in the
      preparation of stable membrane-like surfaces and the commercialisation of sensor
      chips has enabled widespread use of SPR in protein-membrane interactions. One of
      the most popular is Biacore's L1 sensor chip that allows capture of intact
      liposomes or even subcellular preparations. Lipid specificity of protein-membrane
      interactions can, therefore, be easily studied by manipulating the lipid
      composition of the immobilised membrane. The number of published papers has
      increased steadily in the last few years and the examples include domains or
      proteins that participate in cell signalling, pore-forming proteins, membrane
      interacting peptides, coagulation factors, enzymes, amyloidogenic proteins,
      prions, etc. This paper gives a brief overview of different membrane-mimetic
      surfaces that can be prepared on the surface of SPR chips, properties of
      liposomes on the surface of L1 chips and some selected examples of protein
      membrane interactions studied with such system.

PMID- 16584719
TI  - Sphingomyelinase-to-LDL molar ratio determines low density lipoprotein
      aggregation size: biological significance.
AB  - The subendothelial retention of low density lipoproteins (LDL) is believed to be
      the central pathogenic event in atherosclerosis, as stated by the response-to
      retention hypothesis. Sphingomyelinase, an enzyme present in the arteries, has
      been proven to promote LDL aggregation. This study investigates the hypothesis
      that the extent of LDL aggregation is determined by the molar ratio of
      sphingomyelinase (SMase)-to-LDL, rather than the absolute concentrations. A mass
      action model is used to describe the aggregation process, and binding and
      dissociation rate constants are determined by fitting of dynamic light scattering
      data. The model predicts aggregate sizes that agree well with experimental
      observations. This study also tests the hypothesis that monocyte uptake of LDL
      correlates with aggregate size. LDL aggregates of three specific sizes (75, 100,
      and 150 nm) were incubated with J774A.1 cells and the net accumulation of LDL was
      monitored by measuring changes in the cellular cholesterol and protein content.
      Relative to a control sample, cholesterol accumulation was enhanced for aggregate
      sizes of 75 and 150 nm. The intermediate size aggregates, 100 nm, led to a very
      striking result demonstrating that cholesterol accumulation was markedly greater
      than the other samples, and was sufficient to cause cell death. These results
      underscore an important role of colloidal aggregation, and the influence of LDL
      aggregate size, in atherosclerosis.

PMID- 16584721
TI  - A structural model for chorismate synthase from Mycobacterium tuberculosis in
      complex with coenzyme and substrate.
AB  - The enzymes of the shikimate pathway constitute an excellent target for the
      design of new antibacterial agents; chorismate synthase (CS) catalyzes the last
      step of this pathway. The prediction of Mycobacterium tuberculosis (MTB) CS three
      dimensional structure and the geometric docking of the coenzyme FMN and the
      substrate EPSP were performed using the crystal structure of CS from
      Streptococcus pneumoniae as template. Energy minimization of the whole complex
      showed, as expected, that most of the template interactions are preserved in the
      MTB structure, except for HIS11, ARG139 and GLN255. However, novel interactions
      involving ARG111, GLY113 and SER317 were also observed.

PMID- 16584723
TI  - AST-1, a novel ETS-box transcription factor, controls axon guidance and pharynx
      development in C. elegans.
AB  - Neurons send out axons and dendrites over large distances into target areas where
      they eventually form synapses with selected target cells. Axonal navigation is
      controlled by a variety of extracellular signals and neurons express receptors
      only for that subset of signals they need to navigate to their own target area.
      How the expression of axon guidance receptors is regulated is not understood. In
      genetic screens for mutants with axon guidance defects, we identified an ETS
      domain transcription factor, AST-1, specifically required for axon navigation in
      certain classes of interneurons. In addition, ast-1 has a role in the
      differentiation of the ventral cord pioneer neuron AVG. Outside the nervous
      system, ast-1 is essential for morphogenesis of the pharynx. Ast-1 is transiently
      expressed in several classes of neurons (including AVG) during neuronal
      differentiation with a peak expression during late stages of neuronal
      differentiation and axon outgrowth. Ast-1 genetically interacts with other
      transcription factors controlling neuronal differentiation like lin-11 and zag-1
      as well as components of the netrin pathway suggesting that ast-1 might control
      the expression of components of the netrin signal transduction machinery.

PMID- 16584722
TI  - Cloned ferrets produced by somatic cell nuclear transfer.
AB  - Somatic cell nuclear transfer (SCNT) offers great potential for developing better
      animal models of human disease. The domestic ferret (Mustela putorius furo) is an
      ideal animal model for influenza infections and potentially other human
      respiratory diseases such as cystic fibrosis, where mouse models have failed to
      reproduce the human disease phenotype. Here, we report the successful production
      of live cloned, reproductively competent, ferrets using species-specific SCNT
      methodologies. Critical to developing a successful SCNT protocol for the ferret
      was the finding that hormonal treatment, normally used for superovulation,
      adversely affected the developmental potential of recipient oocytes. The onset of
      Oct4 expression was delayed and incomplete in parthenogenetically activated
      oocytes collected from hormone-treated females relative to oocytes collected from
      females naturally mated with vasectomized males. Stimulation induced by mating
      and in vitro oocyte maturation produced the optimal oocyte recipient for SCNT.
      Although nuclear injection and cell fusion produced mid-term fetuses at
      equivalent rates (approximately 3-4%), only cell fusion gave rise to healthy
      surviving clones. Single cell fusion rates and the efficiency of SCNT were also
      enhanced by placing two somatic cells into the perivitelline space. These species
      specific modifications facilitated the birth of live, healthy, and fertile cloned
      ferrets. The development of microsatellite genotyping for domestic ferrets
      confirmed that ferret clones were genetically derived from their respective
      somatic cells and unrelated to their surrogate mother. With this technology, it
      is now feasible to begin generating genetically defined ferrets for studying
      transmissible and inherited human lung diseases. Cloning of the domestic ferret
      may also aid in recovery and conservation of the endangered black-footed ferret
      and European mink.

PMID- 16584724
TI  - MyoD, Myf5, and the calcineurin pathway activate the developmental myosin heavy
      chain genes.
AB  - Myogenesis is accompanied by the activation of two developmental myosin heavy
      chains (MyHCs), embryonic and perinatal, followed by a dramatic decrease in their
      expression during early postnatal life. The pathways that control the
      transcription of these genes have not been previously determined. In this study,
      we identified cis-acting elements and trans-acting factors that regulate the
      expression of these two developmental MyHCs in the mouse. Between 800 and 1000 bp
      of proximal promoter sequence is sufficient to drive muscle-specific expression
      in cell culture. Further, these same regions contain sequences that confer
      downregulation in postnatal life in vivo. For the embryonic MyHC gene, the region
      between -791 bp and -626 bp contains the majority of activating elements. In the
      proximal promoter regions of both genes, we identified two E-box elements that
      work in conjunction to activate transcription, but only the embryonic MyHC E
      boxes bind a complex containing MyoD. In addition, our results reveal activation
      by calcineurin that is transduced only partially by its conventional downstream
      effectors, MEF2 and NFAT. Some common features are shared between the promoters
      of these two genes; however, the mechanisms of their regulation appear distinct.

PMID- 16584725
TI  - Maternal hair--an appropriate matrix for detecting maternal exposure to
      pesticides during pregnancy.
AB  - The detection of exposure of pregnant women to toxicants in the environment is
      important because these compounds can be harmful to the health of the woman and
      her fetus. The aim of this study was to analyze for pesticides/herbicides in
      paired maternal hair and blood samples to determine the most appropriate matrix
      for detecting maternal exposure to these compounds. A total of 449 pregnant women
      were prospectively recruited at midgestation from an agricultural site in the
      Philippines where a preliminary survey indicated significant use at home and on
      the farm of the following compounds: propoxur, cyfluthrin, chlorpyrifos,
      cypermethrin, pretilachlor, bioallethrin, malathion, diazinon, and transfluthrin.
      Paired maternal hair and blood samples were obtained from each subject upon
      recruitment into the study (midgestation) and at birth and were analyzed for the
      above compounds, as well as lindane and DDT [1,1,1-trichloro-2-2-bis(p
      chlorophenyl) ethane], and some of their known metabolites by gas
      chromatography/mass spectrometry. The highest exposure rate was seen for propoxur
      and bioallethrin and maternal hair analysis provided the highest detection rate
      for these two compounds, compared to blood, at both time periods: (1) At
      midgestation, 10.5% positive for propoxur in hair compared to 0.7% in blood
      (P<0.001) and for bioallethrin, 11.9% positive in hair compared to 0% in blood (P
      < or = 0.001), and (2) at birth, 11.8% positive for propoxur in hair compared to
      4% in blood (P < or = 0.001) and for bioallethrin, 7.8% in hair compared to 0% in
      blood (P < or = 0.001). A small number of maternal hair samples were also
      positive for malathion, chlorpyrifos, pretilachlor, and DDT. Only a few of the
      pesticide metabolites were detected, principally 3-phenoxybenzoic acid, malathion
      monocarboxylic acid, and DDE [1,1,dichloro-2-2-bis(p-chlorophenyl)ethylene], and
      they were mostly found in maternal blood. There was a significant association
      between the use of the home spray pesticide, Baygon, and propoxur in maternal
      hair at birth (P=0.001) and between the use of a slow-burning mosquito coil and
      the presence of bioallethrin in maternal hair at midgestation and at birth
      (P=0.001, P < or = 0.041, respectively). There is significant exposure of the
      pregnant woman to pesticides, particularly to pesticides that are used at home.
      Our study demonstrates the advantages of analyzing maternal hair as a readily
      available biologic matrix for studying maternal exposure to toxicants in the
      environment, compared to blood. For propoxur, there was a 3- to 15-fold higher
      detection rate of the pesticide in maternal hair as compared to blood. As for the
      other pesticides, bioallethrin, malathion, chlorpyrifos, and DDT were exclusively
      found in maternal hair compared to blood. On the other hand, pesticide
      metabolites were infrequently found in maternal hair or maternal blood.
      Pesticides in blood most likely represent acute exposure, whereas pesticides in
      hair represent past and/or concurrent exposure. The high sensitivity, wide window
      of exposure, availability, and ease of hair collection are distinct advantages in
      using hair to detect exposure to pesticides among pregnant women. However,
      pesticides in maternal hair may also be secondary to passive exposure and
      therefore not truly representative of the internal pesticide dose. Finally, the
      analysis of maternal hair for pesticides as an index of maternal exposure to
      pesticides in the environment allows the institution of measures to prevent
      further exposure during pregnancy.

PMID- 16584726
TI  - Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic
      pain.
AB  - Diabetic neuropathic pain, an important microvascular complication in diabetes
      mellitus is recognised as one of the most difficult types of pain to treat. A
      lack of the understanding of its aetiology, inadequate relief, development of
      tolerance and potential toxicity of classical antinociceptives warrant the
      investigation of the newer agents to relieve this pain. The aim of the present
      study was to explore the antinociceptive effect of curcumin and its effect on
      tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) release in
      streptozotocin induced diabetic mice. Four weeks after a single intraperitoneal
      injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion
      and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with
      increased plasma glucose and decreased body weights as compared with control
      mice. Chronic treatment with curcumin (15, 30 and 60 mg/kg body weight; p.o.) for
      4 weeks starting from the 4th week of streptozotocin injection significantly
      attenuated thermal hyperalgesia and the hot-plate latencies. Curcumin also
      inhibited the TNF-alpha and NO release in a dose dependent manner. These results
      indicate an antinociceptive activity of curcumin possibly through its inhibitory
      action on NO and TNF-alpha release and point towards its potential to attenuate
      diabetic neuropathic pain.

PMID- 16584727
TI  - Effects of hypoxia on the vasodilator activity of nifedipine and evidence of
      secondary pharmacological properties.
AB  - The effects of hypoxia on the vasodilator response of endothelium-denuded rat
      aortic rings to the calcium channel blocker, nifedipine, were examined. Under
      normoxic conditions, nifedipine (10(-8)-3x10(-6) M) attenuated the contractility
      of noradrenaline precontracted rings in a concentration-dependent manner,
      although the sensitivity was less than what occurs with K+ precontracted tissues.
      Under hypoxic conditions there was no relaxation by nifedipine. When a
      concentration-response curve to noradrenaline was constructed before and in the
      presence of a high concentration of nifedipine (10(-5) M), the response to
      noradrenaline was unaffected in both normoxic and hypoxic conditions. When
      noradrenaline was replaced by phenylephrine (10(-8)-10(-5) M), the maximum
      tension was reduced in the presence of nifedipine to 59+/-6% of the pre
      nifedipine value. Repetition of the experiment in the presence of cocaine (10(-5)
      M) revealed the inhibitory effect of nifedipine on noradrenaline-induced
      contraction, the maximum contraction in the presence of nifedipine falling
      significantly (P<0.005) to 67+/-6% of the pre-nifedipine response. When
      propranolol (10(-7) M) was present in the bath, the maximum contraction to
      noradrenaline was significantly (P<0.05) reduced by nifedipine to 55+/-4% of its
      previous value. The fact that nifedipine was able to inhibit phenylephrine
      induced contractions and relax noradrenaline-precontracted aortic rings confirms
      its calcium channel blocking activity. The failure to inhibit noradrenaline when
      added prior to the noradrenaline-induced contractions suggests an opposing effect
      in addition to calcium channel blockade, which cancels out the attenuation of
      noradrenaline--but not phenylephrine-induced contractions. When neuronal uptake
      of noradrenaline was blocked with cocaine or beta-adrenoceptors were blocked with
      propranolol, the inhibitory effect of nifedipine against noradrenaline-induced
      contractions was revealed. This suggests that the additional property was due to
      blockade of neuronal reuptake or antagonism at beta-adrenoceptors. This study
      also showed that nifedipine is ineffective as a vasodilator in the rat aorta
      under hypoxic conditions.

PMID- 16584728
TI  - Long lasting heat shock stimulation of TRAIL-induced apoptosis in transformed T
      lymphocytes.
AB  - We report that a mild heat shock, that did not impair cell growth, stimulated TNF
      related apoptosis inducing ligand (TRAIL)-mediated apoptosis of leukemic T
      lymphocytes and promyelocytic cells, but not normal human T lymphocytes. The
      death stimulation was maximal when the heat shock was performed at the beginning
      of the exposure to TRAIL. However, enhanced apoptosis was still observed when
      TRAIL was added one day after heat shock. The phenomenon was transcription and
      translation independent suggesting that newly made heat shock proteins were not
      involved. TRAIL-induced apoptosis after heat shock was dependent on caspases and
      FADD and an enhanced FlipL/S processing was noticed. However, since after the
      heat shock FlipL/S processing was transient, events upstream of caspase 8 and
      FADD may be responsible of the long lasting enhanced TRAIL apoptosis observed
      after heat shock. No heat-mediated alteration in the antibody recognition of cell
      surface DR4 and DR5 TRAIL receptors was observed. However, in the presence of
      TRAIL, a long lasting attenuation in the antibody detection of DR4 and DR5 was
      observed in heat shock-treated cells that correlated with the enhanced
      apoptogenic efficiency of TRAIL.

PMID- 16584729
TI  - Keratinocytes from APP/APLP2-deficient mice are impaired in proliferation,
      adhesion and migration in vitro.
AB  - Growing evidence shows that the soluble N-terminal form (sAPPalpha) of the
      amyloid precursor protein (APP) represents an epidermal growth factor fostering
      keratinocyte proliferation, migration and adhesion. APP is a member of a protein
      family including the two mammalian amyloid precursor-like proteins APLP1 and
      APLP2. In the mammalian epidermis, only APP and APLP2 are expressed. APP and
      APLP2-deficient mice die shortly after birth but do not display a specific
      epidermal phenotype. In this report, we investigated the epidermis of APP and/or
      APLP2 knockout mice. Basal keratinocytes showed reduced proliferation in vivo by
      about 40%. Likewise, isolated keratinocytes exhibited reduced proliferation rates
      in vitro, which could be completely rescued by either exogenously added
      recombinant sAPPalpha, or by co-culture with dermal fibroblasts derived from APP
      knockout mice. Moreover, APP-knockout keratinocytes revealed reduced migration
      velocity resulting from severely compromised cell substrate adhesion.
      Keratinocytes from double knockout mice died within the first week of culture,
      indicating essential functions of APP-family members for survival in vitro. Our
      data indicate that sAPPalpha has to be considered as an essential epidermal
      growth factor which, however, in vivo can be functionally compensated to a
      certain extent by other growth factors, e.g., factors released from dermal
      fibroblasts.

PMID- 16584730
TI  - Expression of endostatin in human choroidal neovascular membranes secondary to
      age-related macular degeneration.
AB  - Endostatin is an endogenous angiogenesis inhibitor which requires E-selectin for
      its antiangiogenic activity. The aim of this study was to investigate the
      expression of endostatin in human choroidal neovascular membranes (CNV) secondary
      to age-related macular degeneration (AMD) with regard to vascularization and
      proliferative activity. An interventional case series of 36 patients who
      underwent removal of CNV were retrospectively investigated. Thirty-six CNV were
      analyzed by light microscopic immunohistochemistry for the expression of CD34
      (endothelial cells, EC), CD105 (activated EC), Ki-67 (cell proliferation),
      Cytokeratin 18 (epithelial cells), VEGF (vascular endothelial growth factor), E
      selectin and endostatin. Donor eyes (n=7) including one with AMD were used as
      controls. Endostatin immunoreactivity was present in choroidal vessels of five as
      well as in the retinal pigment epithelium (RPE)-Bruch's membrane complex of two
      donor eyes without AMD. In one eye with AMD, endostatin was detected in RPE,
      Bruch's membrane and choroidal vessels. Ninety-two percent (33/36) of CNV
      disclosed endostatin staining. RPE-Bruch's membrane complex, choroidal vessels
      and stroma were positive in 50% (18/36), 72% (26/36), and 78% (28/36) of the
      membranes, respectively. Both control eyes and CNV expressed all the investigated
      markers except E-selectin being positive only in membranes. Endostatin, an
      endogenous angiogenesis inhibitor, is expressed in CNV and its therapeutic up
      regulation may be a new strategy in the treatment of neovascular AMD.

PMID- 16584731
TI  - Downregulation of survivin expression enhances sensitivity of cultured uveal
      melanoma cells to cisplatin treatment.
AB  - The purpose of this study is to evaluate the effect of a novel anti-apoptotic
      gene, survivin, on the resistance and susceptibility of human uveal melanoma
      cells to apoptosis induced by cisplatin. The sensitivity of human uveal melanoma
      cell lines to apoptosis induced by cisplatin was analyzed by caspase-3 assays.
      The expression of the anti-apoptotic protein, survivin, was examined by flow
      cytometry. Melanoma cells were transfected with either survivin cDNA or survivin
      anti-sense cDNA and examined for susceptibility to cisplatin-induced apoptosis.
      Six human uveal melanoma cell lines were incubated with or without cisplatin and
      cellular proliferation was determined by MTT assays. Significant growth
      inhibition was observed in 3 melanoma cell lines (OMM1, OCM3, and MEL 270). By
      contrast, 3 cell lines (OMM2.5, OMM2.3, and 92-1) were resistant to cisplatin
      induced apoptosis. However, a positive association was observed between
      resistance to cisplatin-induced apoptosis and high expression of the anti
      apoptotic protein, survivin. Up-regulation of survivin by gene transfer enhanced
      resistance to cisplatin-induced apoptosis, while transfection with survivin anti
      sense rendered resistant melanoma cells susceptible to cisplatin. The combination
      of cisplatin and actinomycin D significantly decreased survivin expression and
      enhanced the cisplatin-induced apoptosis of uveal melanoma cells in vitro. These
      data indicate that resistance of some uveal melanoma cells to cisplatin-induced
      apoptosis is controlled by anti-apoptotic proteins, such as survivin, that are
      sensitive to actinomycin D treatment.

PMID- 16584732
TI  - Social interaction and cortisol treatment increase cell addition and radial glia
      fiber density in the diencephalic periventricular zone of adult electric fish,
      Apteronotus leptorhynchus.
AB  - In electric fish, Apteronotus leptorhynchus, both long-term social interaction
      and cortisol treatment potentiates chirping, an electrocommunication behavior
      that functions in aggression. Chirping is controlled by the diencephalic
      prepacemaker nucleus (PPn-C) located just lateral to the ventricle. Cells born in
      adult proliferative zones such as the periventricular zone (PVZ) can migrate
      along radial glial fibers to other brain regions, including the PPn-C. We
      examined whether social interactions or cortisol treatment influenced cell
      addition and radial glia fiber formation by (1) pairing fish (4 or 7 days) or (2)
      implanting fish with cortisol (7 or 14 days). Adult fish were injected with
      bromodeoxyuridine 3 days before sacrifice to mark cells that were recently added.
      Other fish were sacrificed after 1 or 7 days of treatment to examine vimentin
      immunoreactivity (IR), a measure of radial glial fiber density. Paired fish had
      more cell addition than isolated fish at 7 days, coinciding temporally with the
      onset of socially induced increase in chirping behavior. Paired fish also had
      higher vimentin IR at 1 and 7 days. For both cell addition and vimentin IR, the
      effect was regionally specific, increasing in the PVZ adjacent to the PPn-C, but
      not in surrounding regions. Cortisol increased cell addition at 7 days,
      correlating with the onset of cortisol-induced changes in chirping, and in a
      regionally specific manner. Cortisol for 14 days increased cell addition, and
      cortisol for 7 days increased vimentin IR but in a regionally non-specific
      manner. The correlation between treatment-induced changes in chirping and
      regionally specific increases in cell addition, and radial glial fiber formation
      suggests a causal relationship between such behavioral and brain plasticity in
      adults, but this hypothesis will require further testing.

PMID- 16584733
TI  - Serial intravascular ultrasound evidence of both plaque stabilization and lesion
      progression in patients with ruptured coronary plaques: effects of statin therapy
      on ruptured coronary plaque.
AB  - Using serial intravascular ultrasound (IVUS), we evaluated the natural evolution
      of non-culprit/non-target lesion ruptured coronary plaques and assessed the
      impact of statin therapy. Twenty-eight patients with non-stenotic ruptured
      plaques underwent baseline and 12-month follow-up IVUS studies; half were treated
      with statins. Standard IVUS analyses were performed. Complete healing of ruptured
      plaques was observed in four (29%) statin-treated patients and no non-statin
      treated patients (p=0.049). Statin-treated patients had an increase in lumen area
      of 0.4+/-0.8 mm2 (versus a decrease in lumen area of -0.6+/-1.0 mm2 in non-statin
      treated patients, p=0.007) and no change in plaque area (versus an increase in
      plaque area of 0.6+/-0.9 mm2, p=0.051). During 1-year follow-up, target lesion
      revascularization was performed in three non-statin-treated patients (21%) and no
      statin-treated patient (p=0.11). Compared to lesions that did not require
      revascularization, lesions requiring revascularization had a decrease in lumen
      area (-1.7+/-1.4 mm2 versus 0.1+/-0.8 mm2, p=0.001) as well as an increase in
      plaque area (1.6+/-1.0 mm2 versus 0.1+/-0.7 mm2, p=0.002). In conclusion, the
      current observational follow-up IVUS study showed beneficial effects of statin
      treatment on reduction of revascularization rates and stabilization of non
      culprit/non-target lesion plaque ruptures without significant stenosis.
      Conversely, healing of non-statin-treated non-culprit/non-target lesion plaque
      ruptures can be responsible for lesion progression requiring revascularization.

PMID- 16584734
TI  - Decreased plasma extracellular superoxide dismutase level in patients with
      vasospastic angina.
AB  - OBJECTIVE: Extracellular superoxide dismutase (EC-SOD) is the major extracellular
      scavenger of superoxides, and one of the main regulators of nitric oxide
      bioactivity in vessel walls. Here, we examined whether plasma EC-SOD level was
      associated with vasospastic angina (VSA), and if it was a risk factor for VSA.
      METHODS AND RESULTS: We assigned 105 patients with normal or mildly stenotic
      coronary arteries into either a VSA (n=58) or chest pain syndrome (CPS) (n=47)
      groups. Plasma EC-SOD and other biochemical variables were measured, and major
      coronary risk factors were assessed. Results showed that apart from smoking
      status there were no significant differences in patient characteristics and
      biochemical variables between the two groups. In the VSA group, prevalence of
      smoking was significantly higher (53% versus 26%, p=0.0055), and plasma EC-SOD
      level was significantly lower (68.9+/-18.5 ng/ml versus 83.8+/-25.9 ng/ml;
      p=0.0009). Not only smoking (OR 2.742, 95% CI 1.032-7.287, p=0.0431) but also
      plasma EC-SOD (OR 0.971, 95% CI 0.949-0.993, p=0.0102) was an independent risk
      factor for VSA. CONCLUSIONS: In patients with VSA, plasma EC-SOD level was
      substantially reduced. Furthermore, plasma EC-SOD level followed by cigarette
      smoking was the most predictive risk factor for coronary spasms.

PMID- 16584735
TI  - Determination of joint efforts in the human body during maximum ramp pushing
      efforts.
AB  - Determining with accuracy, the internal efforts in the human body is a great
      challenge in Biomechanics, particularly in Physical Therapy and Ergonomics. In
      this context, the present study develops a human body model that permits a non
      invasive determination of the joint efforts produced by a seated subject
      performing maximum ramp pushing efforts. The joint interactions during these
      experiments are provided by a dynamic inverse model of the human body, using a
      symbolically generated recursive Newton-Euler formalism. The theoretical
      investigation is presented in two steps, with increasing complexity and
      relevance:The dynamic model confirms some previous studies of the effects of
      biomechanical factors on the performance of the task and is proposed as an
      accurate method for determining the joint efforts in dynamic contexts. Finally,
      this application is a preliminary benchmark case that will be extended to:
      *physical therapy, in order to analyse the joint and muscle efforts in various
      motion contexts, particularly for patients with fibromyalgia and patients with
      lumbar diseases; *accidentology, in order to analyse and simulate car occupant
      dynamics before a crash.

PMID- 16584736
TI  - On the role of anisotropy of membrane constituents in formation of a membrane
      neck during budding of a multicomponent membrane.
AB  - The expression for the isotropic membrane bending energy was generalized for the
      case of a multicomponent membrane where the membrane constituents (single
      molecules or small complexes of molecules-membrane inclusions) were assumed to be
      anisotropic. Using this generalized expression for the membrane energy it was
      shown that the change of intrinsic shape of membrane components may induce first
      order-like shape transitions leading to the formation of a membrane neck. The
      predicted discontinuous membrane shape transition and the concomitant lateral
      segregation of membrane components were applied to study membrane budding. Based
      on the results presented we conclude that the budding process might be driven by
      accumulation of anisotropic membrane components in the necks connecting the bud
      and the parent membrane, and by accumulation of isotropic (conical) membrane
      components on the bud. Both processes may strongly depend on the intrinsic shape
      of membrane components and on the direct interactions between them.

PMID- 16584737
TI  - Prediction of the hip joint centre in adults, children, and patients with
      cerebral palsy based on magnetic resonance imaging.
AB  - The location of the hip joint centre (HJC) is required for calculations of hip
      moments, the location and orientation of the femur, and muscle lengths and lever
      arms. In clinical gait analysis, the HJC is normally estimated using regression
      equations based on normative data obtained from adult populations. There is
      limited relevant anthropometric data available for children, despite the fact
      that clinical gait analysis is predominantly used for the assessment of children
      with cerebral palsy. In this study, pelvic MRI scans were taken of eight adults
      (ages 23-40), 14 healthy children (ages 5-13) and 10 children with spastic
      diplegic cerebral palsy (ages 6-13). Relevant anatomical landmarks were located
      in the scans, and the HJC location in pelvic coordinates was found by fitting a
      sphere to points identified on the femoral head. The predictions of three common
      regression equations for HJC location were compared to those found directly from
      MRI. Maximum absolute errors of 31 mm were found in adults, 26 mm in children,
      and 31 mm in the cerebral palsy group. Results from regression analysis and leave
      one-out cross-validation techniques on the MRI data suggested that the best
      predictors of HJC location were: pelvic depth for the antero-posterior direction;
      pelvic width and leg length for the supero-inferior direction; and pelvic depth
      and pelvic width for the medio-lateral direction. For single-variable regression,
      the exclusion of leg length and pelvic depth from the latter two regression
      equations is proposed. Regression equations could be generalised across adults,
      children and the cerebral palsy group.

PMID- 16584738
TI  - Comparison between tripod and skin-fixed recording of scapular motion.
AB  - Non-invasive dynamical measurements of 3D scapular motion can be performed easily
      by attachment of a 6 DOF electromagnetic receiver onto the skin above the
      acromion. To quantify the introduction of possible errors due to skin
      displacement, we assessed 3D scapular positions on n=8 subjects by both tripod
      and skin-fixed method. Error analysis included the variables method (tripod, skin
      fixed simultaneously with tripod, separate skin-fixed at 0 and 0.25Hz of
      elevation speed), plane of elevation (0 degrees and 90 degrees ) and observation
      (receiver replacement: n=3). Inter-individual 'group' differences depended on
      elevation plane and showed an average underestimation of scapular rotation of 6.5
      degrees (worst case 13 degrees ) using the skin-fixed method. Only the group
      RMSE, not the individual RMSE, could be successfully lowered using linear
      regression (to about 2 degrees ). Inter-trial reliability (RMSE <3.24 degrees ,
      ICC>0.94) and RMSE between 0 and 0.25Hz recordings (about 2.5 degrees ) were
      satisfactory. Intra-observer RMSE after replacement of the skin-fixed receiver
      was 5 degrees . The skin-fixed method is suitable for dynamic recordings of
      scapular rotations; however, measurements are precise only when the acromion
      receiver is not replaced. Combined with a relatively low accuracy, we conclude
      that the skin-fixed method should be used only in combination with tripod
      'calibration'.

PMID- 16584739
TI  - Dynamic modelling of prosthetic chorded mitral valves using the immersed boundary
      method.
AB  - Current artificial heart valves either have limited lifespan or require the
      recipient to be on permanent anticoagulation therapy. In this paper, effort is
      made to assess a newly developed bileaflet valve prosthesis made of synthetic
      flexible leaflet materials, whose geometry and material properties are based on
      those of the native mitral valve, with a view to providing superior options for
      mitral valve replacement. Computational analysis is employed to evaluate the
      geometric and material design of the valve, by investigation of its mechanical
      behaviour and unsteady flow characteristics. The immersed boundary (IB) method is
      used for the dynamic modelling of the large deformation of the valve leaflets and
      the fluid-structure interactions. The IB simulation is first validated for the
      aortic prosthesis subjected to a hydrostatic loading. The predicted displacement
      fields by IB are compared with those obtained using ANSYS, as well as with
      experimental measurements. Good quantitative agreement is obtained. Moreover,
      known failure regions of aortic prostheses are identified. The dynamic behaviour
      of the valve designs is then simulated under four physiological pulsatile flows.
      Experimental pressure gradients for opening and closure of the valves are in good
      agreement with IB predictions for all flow rates for both aortic and mitral
      designs. Importantly, the simulations predicted improved physiological
      haemodynamics for the novel mitral design. Limitation of the current IB model is
      also discussed. We conclude that the IB model can be developed to be an extremely
      effective dynamic simulation tool to aid prosthesis design.

PMID- 16584740
TI  - The influence of material property and morphological parameters on specimen
      specific finite element models of porcine vertebral bodies.
AB  - The use of finite element (FE) methods in spinal research is increasing, but
      there is only limited information available on the influence of different input
      parameters on the model predictions. The aim of this study was to investigate the
      role of these parameters in FE models of the vertebral body. Experimental tests
      were undertaken on porcine lumbar vertebral bodies and scans of the specimens
      were used to create specimen-specific FE models. Three models were created for
      each specimen with combinations of generic and specimen-specific parameters.
      Stiffness and strength predictions were also made directly from the specimen
      trabecular bone volume fraction (BVF) and cross-sectional area (CSA). The
      agreement between the experimental results and the FE models with generic
      morphology was poorer (concordance coefficients = 0.058, 0.125 for stiffness,
      strength) than those made from the BVF and CSA (concordance coefficients = 0.638,
      0.609). The greatest levels of agreement were found with the morphologically
      specific models including element-specific material properties (concordance
      coefficients = 0.881, 0.752). This indicates that highly specific models, both in
      terms of morphology and bone quality, are necessary if the FE tool is to be used
      effectively for spinal research and clinical practice.

PMID- 16584741
TI  - Determination of phospholipid fatty acids in biological samples by solid-phase
      extraction and fast gas chromatography.
AB  - A new method for the determination of phospholipid fatty acids in biological
      samples, combination of solid-phase extraction (SPE) and fast gas chromatography
      (GC) was developed. Its application to human plasma and human erythrocytes showed
      to be robust and reliable for quick and correct identification in routine
      analysis.

PMID- 16584742
TI  - Low-pressure gas chromatography-ion trap mass spectrometry for the fast
      determination of polycyclic aromatic hydrocarbons in air samples.
AB  - A low-pressure gas chromatography-ion trap mass spectrometry (LPGC-ITMS) method
      was investigated to shorten the analysis time for 18 US Environmental Protection
      Agency priority listed polycyclic aromatic hydrocarbons (PAHs). Their elution was
      optimised with a short, wide-bore column coupled to a deactivated capillary at
      the inlet end and with a long, conventional column to compare their analytical
      performance. The analytical figures of merit under optimal LPGC-ITMS conditions
      were determined with respect to chromatographic separation, S/N ratio, limit of
      detection and precision. The peak width at half height of 1.5s matched the ITMS
      duty cycle. Up to 16 PAHs in the molecular weight (MW) range of 128-278 Da could
      be separated in a very short time, i.e. less than 13 min using LPGC-ITMS, whereas
      with conventional GC-MS, it took approximately 40 min. However, LPGC-ITMS has a
      limited loss of separation power compared to that of conventional GC-MS due to
      the occurrence of three critical pairs for high-MW PAHs. For a practical
      evaluation, the LPGC-ITMS approach was applied to the determination of PAHs in
      gas and aerosol phase samples collected in the ambient air of Hasselt, Belgium.

PMID- 16584743
TI  - Purification of decorin core protein from human lung tissue.
AB  - A chromatographic method to purify decorin core protein from human lung tissue is
      described. The method is simple and rapid, using a combination of two-anion
      exchange and one reversed phase chromatography steps and the enzymatic digestion
      with chondroitinase ABC. Approximately 170 microg decorin core protein were
      purified from 25 g of lung tissue with an enrichment factor of 1800-fold relative
      to the initial protein content. SDS-PAGE analysis of the final product revealed a
      single 42 kDa protein band, which was recognized by anti-decorin antibodies upon
      Western blotting and identified by mass spectrometry. Further digestion with
      PNGase F evidenced the presence of three N-linked oligosaccharides on the core
      protein. This method forms the basis for studying structural alterations of
      decorin related to the pathology of diseases where tissue destruction plays a
      role.

PMID- 16584744
TI  - Using the liquid nature of the stationary phase in countercurrent chromatography.
      IV. The cocurrent CCC method.
AB  - The retention volumes of solutes in countercurrent chromatography (CCC) are
      directly proportional to their distribution coefficients, K(D) in the biphasic
      liquid system used as mobile and stationary phase in the CCC column. The
      cocurrent CCC method consists in putting the liquid "stationary" phase in slow
      motion in the same direction as the mobile phase. A mixture of five steroid
      compounds of widely differing polarities was used as a test mixture to evaluate
      the capabilities of the method with the biphasic liquid system made of
      water/methanol/ethyl acetate/heptane 6/5/6/5 (v/v) and a 53 mL CCC column of the
      coil planet centrifuge type. It is shown that the chromatographic resolution
      obtained in cocurrent CCC is very good because the solute band broadening is
      minimized as long as the solute is located inside the "stationary" phase. Pushing
      the method at its limits, it is demonstrated that the five steroids can still be
      (partly) separated when the flow rate of the two liquid phases is the same (2
      mL/min). This is due to the higher volume of upper phase (72% of the column
      volume) contained inside the CCC column producing a lower linear speed compared
      to the aqueous lower phase linear speed. The capabilities of the cocurrent CCC
      method compare well with those of the gradient elution method in HPLC. Continuous
      detection is a problem due to the fact that two immiscible liquid phases elute
      from the column. It was partly solved using an evaporative light scattering
      detector.

PMID- 16584746
TI  - Selective pressures at a codon-level predict deleterious mutations in human
      disease genes.
AB  - Deleterious mutations affecting biological function of proteins are constantly
      being rejected by purifying selection from the gene pool. The non
      synonymous/synonymous substitution rate ratio (omega) is a measure of selective
      pressure on amino acid replacement mutations for protein-coding genes. Different
      methods have been developed in order to predict non-synonymous changes affecting
      gene function. However, none has considered the estimation of selective
      constraints acting on protein residues. Here, we have used codon-based maximum
      likelihood models in order to estimate the selective pressures on the individual
      amino acid residues of a well-known model protein: p53. We demonstrate that the
      number of residues under strong purifying selection in p53 is much higher than
      those that are strictly conserved during the evolution of the species. In
      agreement with theoretical expectations, residues that have been noted to be of
      structural relevance, or in direct association with DNA, were among those showing
      the highest signals of purifying selection. Conversely, those changing according
      to a neutral, or nearly neutral mode of evolution, were observed to be irrelevant
      for protein function. Finally, using more than 40 human disease genes, we
      demonstrate that residues evolving under strong selective pressures (omega<0.1)
      are significantly associated (p<0.01) with human disease. We hypothesize that non
      synonymous change on amino acids showing omega<0.1 will most likely affect
      protein function. The application of this evolutionary prediction at a genomic
      scale will provide an a priori hypothesis of the phenotypic effect of non
      synonymous coding single nucleotide polymorphisms (SNPs) in the human genome.

PMID- 16584748
TI  - Hyaluronan: the local solution conformation determined by NMR and computer
      modeling is close to a contracted left-handed 4-fold helix.
AB  - The polysaccharide hyaluronan (HA) is a ubiquitous component of the vertebrate
      extracellular matrix with diverse physiological roles from space-filling to
      acting as a scaffold for other macromolecules. The molecular interactions
      responsible for these solution properties have been the subject of much debate
      and, primarily due to the lack of residue-specific experimental data, no
      consensus model for the three-dimensional conformation nor dynamics of HA in
      solution has emerged. Here, the solution conformation of HA is investigated using
      molecular dynamics (MD) simulations and high-field nuclear magnetic resonance
      (NMR). In contrast to previous studies, MD simulations incorporated explicit
      water molecules and sodium ions, while NMR experiments utilized (15)N-enriched
      oligosaccharides to allow residue-specific information to be obtained. The
      resultant average conformation is predicted to be almost a contracted left-handed
      4-fold helix; i.e. similar to that observed for sodium hyaluronate fibers by X
      ray diffraction, but with the acetamido side-chain trans to H(2). The glycosidic
      linkages and acetamido side-chains are predicted to have standard deviation
      rotations of 13 degrees and 18 degrees around their mean conformations in free
      solution, respectively, and are not observed to be stabilized by strong
      intramolecular hydrogen bonds as X-ray fiber diffraction refinements describe for
      the solid-state. Rather, weak and transient hydrogen bonds that are in rapid
      interchange with solvent molecules are predicted. These predictions are
      quantitatively consistent with demanding residue-specific NMR data and correspond
      to an HA molecule that is rod-like as an oligosaccharide and behaves as a
      stiffened random coil at large molecular mass, in close agreement with previous
      hydrodynamic observations. This new description of the solution conformation of
      HA is consistent with all available experimental data and accounts for its
      viscoelastic space-filling properties. This representation can be used as a basis
      for modeling the association between HA and proteins, which will elucidate
      important aspects of extracellular matrix assembly.

PMID- 16584747
TI  - Crystal structure of a novel viral protease with a serine/lysine catalytic dyad
      mechanism.
AB  - The blotched snakehead virus (BSNV), an aquatic birnavirus, encodes a polyprotein
      (NH2-pVP2-X-VP4-VP3-COOH) that is processed through the proteolytic activity of
      its own protease (VP4) to liberate itself and the viral proteins pVP2, X and VP3.
      The protein pVP2 is further processed by VP4 to give rise to the capsid protein
      VP2 and four structural peptides. We report here the crystal structure of a VP4
      protease from BSNV, which displays a catalytic serine/lysine dyad in its active
      site. This is the first crystal structure of a birnavirus protease and the first
      crystal structure of a viral protease that utilizes a lysine general base in its
      catalytic mechanism. The topology of the VP4 substrate binding site is consistent
      with the enzymes substrate specificity and a nucleophilic attack from the si-face
      of the substrates scissile bond. Despite low levels of sequence identity, VP4
      shows similarities in its active site to other characterized Ser/Lys proteases
      such as signal peptidase, LexA protease and Lon protease. Together, the structure
      of VP4 provides insights into the mechanism of a recently characterized clan of
      serine proteases that utilize a lysine general base and reveals the structure of
      potential targets for antiviral therapy, especially for other related and
      economically important viruses, such as infectious bursal disease virus in
      poultry and infectious pancreatic necrosis virus in aquaculture.

PMID- 16584749
TI  - Error propagation across levels of organization: from chemical stability of
      ribosomal RNA to developmental stability.
AB  - My hypothesis integrates molecular and whole-organism levels of development. A
      physico-chemical property of nucleotides (their dipole moment), confers
      structural thermostability on double-stranded sequences, and decreases chemical
      stability of single-stranded sequences. According to this approach, low ribosomal
      RNA stability should decrease the precision of protein synthesis and whole
      organism developmental stability. Indeed, substitution frequencies in pseudogenes
      are proportional to the subtraction of the dipole moment of the substituting
      nucleotide from that of the substituted one, and developmental instability,
      estimated by morphological fluctuating asymmetry (FA), correlates with mammal 12s
      rRNA base content of loop (but not stem) regions. In lizards, fit to the single
      strand rationale of sequence chemical stability decreases with the level of
      poikilothermy of the investigated lizard family, suggesting interactions between
      changes in body temperature, ribosomal structure and developmental instability.
      Results confirm the hypothesis (less than for 12s rRNA) in: third codon positions
      of cytochrome B, probably because, unlike rRNAs, specific mRNAs affect only the
      protein they code; and 16s rRNA, apparently because its base composition is more
      affected by genome-wide mutational biases than that of 12s rRNA.

PMID- 16584750
TI  - A reduced mathematical model of the acute inflammatory response: I. Derivation of
      model and analysis of anti-inflammation.
AB  - The acute inflammatory response, triggered by a variety of biological or physical
      stresses on an organism, is a delicate system of checks and balances that,
      although aimed at promoting healing and restoring homeostasis, can result in
      undesired and occasionally lethal physiological responses. In this work, we
      derive a reduced conceptual model for the acute inflammatory response to
      infection, built up from consideration of direct interactions of fundamental
      effectors. We harness this model to explore the importance of dynamic anti
      inflammation in promoting resolution of infection and homeostasis. Further, we
      offer a clinical correlation between model predictions and potential therapeutic
      interventions based on modulation of immunity by anti-inflammatory agents.

PMID- 16584752
TI  - Study of a novel indolin-2-ketone compound Z24 induced hepatotoxicity by NMR
      spectroscopy-based metabonomics of rat urine, blood plasma, and liver extracts.
AB  - Antiangiogenic compound has been believed to be an ideal drug in the current
      cancer biological therapy, but the angiogenesis inhibitors suffer setback for
      unknown toxicity now. A novel synthetic indolin-s-ketone small molecular
      compound, 3Z-3-[((1)H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H
      indol-2-one (Z24) can inhibit angiogenesis in new blood vessels. The
      hepatotoxicity effects of Z24 oral administration (dosed at 60, 130 and 200
      mg/kg) have been investigated in female Wistar rats by using metabonomic analysis
      of (1)H NMR spectra of urine, plasma and liver extracts, as well as by clinical
      chemistry analysis, liver histopathology and electron micrographs examination.
      The (1)H NMR spectra of the biofluids were analyzed visually and via pattern
      recognition by using principal component analysis. The metabonomic trajectory
      analysis on the time-related hepatotoxicity of Z24 was carried out based on the
      (1)H NMR spectra of urine samples, which were collected daily predose and
      postdose over an 8-day period. Urinary excretion of citrate, lactate, 2-oxo
      glutarate and succinate increased following Z24 dosing. Increased plasma levels
      of lactate, TMAO and lipid were observed, with concomitant decrease in the level
      of glucose and phosphatidylcholine. Metabolic profiling on aqueous soluble
      extracts of liver tissues with the high dose level of Z24 showed an increase in
      lactate and glutamine, together with a decrease in glucose, glycogen and choline.
      On the other hand, studies on lipid soluble extracts of liver tissues with the
      high dose level of Z24 showed increased level in lipid triglycerides and
      decreased level in unsaturated fatty acids and phosphatidylcholine. Moreover, the
      most notable effect of Z24 on the metabolism was the reduction in the urinary
      levels of creatinine and TMAO and the increase in acetate, citrate, succinate and
      2-oxo-glutamate with time dependence. The results indicate that in rats Z24
      inhibits mitochondrial function through altering the energy and lipid metabolism,
      which results in the accumulation of free fatty acids and lactate because of the
      lack of aerobic respiration. These data show that the metabonomic approach
      represents a promising new technology for the toxicological mechanism study.

PMID- 16584751
TI  - Effects of ovariectomy and chronic estradiol administration on pituitary-thyroid
      axis in adult rats.
AB  - The effects of ovariectomy (Ovx) and of ovariectomy followed by chronic estradiol
      dipropionate administration (Ovx EDP) on the structure and function of the
      pituitary-thyroid axis were examined in the rat. Pituitary TSH cells and thyroid
      tissue were histologically, immunohistochemically and stereologically
      investigated. Serum TSH and T(4) levels were determined by RIA. Ovx did not
      affect pituitary weight, but subsequent treatment with EDP led to its more than
      two-fold increase (p<0.05). After ovariectomy, the cellular volume of pituitary
      TSH-immunoreactive cells increased by 28%, p<0.05 compared to sham-operated
      animals (SO). Treatment of Ovx rats with EDP partially reversed this change.
      However, the relative volume density of thyrotrophs decreased in comparison to
      the Ovx and SO groups (by 18% and 23%, p<0.05, respectively). No statistically
      significant differences in serum TSH levels were observed between the
      experimental groups. In thyroid tissue both peripheral and central follicles
      responded to Ovx and EDP treatments. Compared to SO rats, the relative volume
      densities of the follicles and colloid were increased (by 14% and 30%, p<0.05,
      respectively) in Ovx rats. Chronic EDP treatment of Ovx rats reversed these
      changes to the pre-ovariectomy state. Hyperplasia of thyroid follicular cells and
      a significant reduction (by 21%, p<0.05) of the serum level of T(4) were
      detected. In conclusion, estradiol deficiency and chronic treatment affected
      pituitary TSH cells and thyroid tissue. The sum effect of Ovx on the pituitary
      thyroid axis was slightly stimulatory. Subsequent EDP treatment decreased thyroid
      functioning but at the same time preserved serum TSH at the control level.

PMID- 16584753
TI  - Inhibition of cyclooxygenase-2 expression by zinc-chelator in retinal ischemia.
AB  - The zinc ion (Zn2+) is abundant in neurons. However, excessive Zn2+ can induce
      neuronal cell death. This study examined the role of Zn2+ in transient retinal
      ischemia in adult male rats. The rats were sacrificed 4-24 h after retinal
      ischemia by high intra-ocular pressure, and the retinas were prepared for
      microscopic examination of retinal cell degeneration, and fluorescence microscopy
      using zinquin ethyl ester as the zinc ion-specific probe. Moreover, COX-2
      expression was observed by Western blotting. In control retinas, there was a low
      Zn2+ concentration in the inner plexiform layer (IPL), a high Zn2+ concentration
      in the outer plexiform layer (OPL), and no detectable Zn2+ in either the ganglion
      cell layer (GCL) or the inner nuclear layer (INL). In contrast, in the retinas
      exposed to ischemia without the administration of the zinc ion chelators (Ca2+
      EDTA and TPEN), Zn2+ deposits were found in the IPL and INL beginning 4 h after
      ischemia and degeneration of neurons was found in the GCL and INL. Less Zn2+
      accumulation in the IPL and INL and less neuronal degeneration in the GCL and INL
      were found in the retinas treated with Ca2+-EDTA or TPEN before ischemia.
      Furthermore, the COX-2 protein levels increased 4-8 h after retinal ischemia, and
      chelation of zinc ion inhibited this effect. These results suggest that the
      accumulation of Zn2+ following an ischemic insult can cause retinal degeneration
      and induce abnormal COX-2 expression.

PMID- 16584754
TI  - Quantification of polychlorinated biphenyls in plastic granulates from the
      recycling of cables - Reference materials and interlaboratory comparison.
AB  - A procedure for the quantification of the PCB marker congeners 28, 52, 101, 138,
      153, 180 in plastic waste form the recycling of cables in the range of content
      between 0.1 mgkg(-1) and 20 mgkg(-1) was validated. Representative reference
      materials for laboratory analyses were produced using granulates from different
      recycling processes. The method development included aspects of grinding,
      sieving, homogenising as well as the comparison of extraction methods and
      chromatographic conditions. The validated procedure foresees grinding of the
      technical sample to an upper particle size limit of 0.50mm followed by extraction
      with an unpolar solvent such as n-hexane and gas chromatographic determination.
      LOD and LOQ for individual congeners ranged between 0.01 mgkg(-1) and 0.08 mgkg(
      1). Electron capture detection (ECD) and mass selective detection (MS) were
      equivalent if chromatographic conditions were appropriately selected. The
      application of MS was advantageous in presence of significant amounts of
      interfering components which have been found in some cables. Three reference
      materials containing the marker congeners in the range of 0.1 mgkg(-1)-5 mgkg(-1)
      were submitted to a final validation intercomparison with 23 selected field
      laboratories using the developed method. Relative reproducibility standard
      deviations varied between 15% and 33%.

PMID- 16584755
TI  - Elemental analysis of ash residue from combustion of CCA treated wood waste
      before and after electrodialytic extraction.
AB  - Element distribution in a combined fly ash and bottom ash from combustion of
      copper chromate arsenate (CCA) treated wood waste was investigated by scanning
      electron microscopy (SEM/EDX) before and after electrodialytic extraction. The
      untreated ash contained various particles, including pieces of incompletely
      combusted wood rich in Cr and Ca, and irregular particles rich in Si, Al and K.
      Cr was also found incorporated in silica-based matrix particles. As was
      associated with Ca in porous (char) particles, indicating that Ca-arsenates had
      been formed during combustion. Cu was associated with Cr in the incompletely
      combusted wood pieces and was also found in almost pure form in a surface layer
      of some matrix particles - indicating surface condensation of volatile Cu
      species. In treated ash, Ca and As were no longer found together, indicating that
      Ca-arsenates had been dissolved due to the electrodialytic treatment. Instead
      particles rich in Ca and S were now found, indicating precipitation of Ca
      sulphates due to addition of sulphuric acid in connection with the
      electrodialytic treatment. Cu and Cr were still found associated with
      incompletely combusted wood particles and incorporated in matrix particles.
      Chemical analyses of untreated and treated ash confirmed that most As, but only
      smaller amounts of Cu and Cr was removed due to the electrodialytic extraction.
      Overall metal contents in the original ash residue were: 1.4 g As, 2.76 g Cu and
      2.48 g Cr, after electrodialytic extraction these amounts were reduced by 86% for
      As, 15% for Cu and 33% for Cr.

PMID- 16584756
TI  - Removal of estrogenic activity of natural steroidal hormone estrone by
      ligninolytic enzymes from white rot fungi.
AB  - Natural steroidal hormone estrone (E1) was treated with the white rot fungus
      Phanerochaete sordida YK-624 under ligninolytic condition with low-nitrogen and
      high-carbon culture medium. E1 decreased by 98% after 5 d of treatment and the
      activities of ligninolytic enzymes, manganese peroxidase (MnP) and laccase, were
      detected during treatment, which suggested that the disappearance of E1 is
      related to ligninolytic enzymes produced extracellularly by white rot fungus.
      Therefore, E1 was treated with MnP and laccase prepared from the culture of white
      rot fungi. HPLC analysis demonstrated that E1 disappeared completely in the
      reaction mixture after 1 h of treatment with either MnP or laccase. Using the
      yeast two-hybrid assay system, it was also confirmed that both enzymatic
      treatments completely removed the estrogenic activity of E1 after 2 h. These
      results strongly suggest that ligninolytic enzymes are effective in removing the
      estrogenic activity of E1.

PMID- 16584757
TI  - Spatial mapping of temporal risk characteristics to improve environmental health
      risk identification: a case study of a dengue epidemic in Taiwan.
AB  - Mapping uneven events, such as disease cases or pollutants, is a basic but
      important procedure for analyzing regional relationships and variation in public
      health and environmental agencies. The purpose of mapping is to find out the
      spatial clustering of uneven events and identify spatial risk areas, which could
      lead to potential environmental hazards or epidemics. Meanwhile, more hypotheses
      could be generated through mapping process for further investigations. This paper
      proposed a novel spatial-temporal approach to focusing on: (1) how often these
      uneven cases occur, (2) how long these cases persist and (3) how significant
      cases occur in consecutive periods across the study area. The proposed model was
      applied to the dengue fever epidemic in Taiwan in 2002 as a case study, which was
      the worst epidemic in the last 60 years. This approach provides procedures to
      identify spatial health risk levels with temporal characteristics and assists in
      generating hypothesis that will be investigated in further detail.

PMID- 16584758
TI  - Apoptosis is not altered by clomiphene citrate in pseudopregnant rat uteri.
AB  - Clomiphene citrate (CC) remains one of the most often prescribed synthetic
      oestrogens used in the treatment of infertility even though the ensuing pregnancy
      rates are low. CC alters the uterine environment on most levels. Ovariectomised
      rats were treated with 5 mg progesterone (P) for 3 days and a 0.5 microg
      injection of oestrogen (E) on the third day (PP(PE)) thus inducing
      pseudopregnancy and rendering the uterus receptive to implantation 24 h later.
      Using this model, we investigated apoptosis in the rat uterus treated with 0.25
      mg CC given prior to the PP(PE) treatment. Apoptotic cells in the uterus were
      localised using TUNEL and visualised with a FITC marker. There was a similar
      increase in apoptosis in the uterine luminal epithelium in the PP(PE) and
      CCPP(PE) treated animals; no changes were observed in apoptosis in the other
      uterine compartments when compared to the control. The CCPP(PE)-treated tissue
      showed tall epithelial cells with long microvilli while the PP(PE) tissue had
      short microvilli and low cuboidal epithelium. These results suggest that CC does
      not disrupt the normal apoptotic activity seen at implantation, but does change
      the morphology of the luminal epithelium, suggesting that these cellular changes
      could influence successful implantation.

PMID- 16584759
TI  - Open versus laparoscopic simultaneous bilateral adrenalectomy.
AB  - OBJECTIVES: To compare our experience with synchronous bilateral adrenalectomy
      using laparoscopic and open techniques. Laparoscopic adrenalectomy has become the
      reference standard for management of benign unilateral adrenal pathologic
      findings. METHODS: This was a nonrandomized retrospective chart review of 12
      known patients who underwent simultaneous bilateral adrenalectomy, comparing five
      laparoscopic and seven open procedures. One urologic surgeon performed all
      laparoscopic cases, and one general surgeon performed all open procedures.
      RESULTS: All patients had Cushing's disease or syndrome. The average patient age
      was 47.4 years (range 24 to 71) and 42.4 years (range 19 to 70), with an average
      body mass index of 38.2 kg/m2 and 36.0 kg/m2 for the laparoscopic and open
      groups, respectively. The operating time was on average 60 minutes longer for the
      laparoscopic group. No open conversions were necessary. The median blood loss
      (100 versus 500 mL, P < 0.01) and hematocrit drop (8.5% versus 12.6%, P = 0.05)
      were lower for the laparoscopic group. The transfusion rates and hospital stay
      trended lower in the laparoscopic group (20% versus 57% and 3 versus 8.5 days,
      respectively). Specimen weights for both the right and left glands trended larger
      for the laparoscopic group. The complication rates were similar between groups at
      60% for the laparoscopic versus 71% for the open groups. CONCLUSIONS:
      Simultaneous laparoscopic bilateral adrenalectomy is safe and effective. Compared
      with the open approach, it resulted in decreased blood loss, lower transfusion
      rate, and a trend toward a shorter hospital stay, although the operating time was
      longer. The laparoscopic approach should be the treatment of choice for bilateral
      adrenalectomy.

PMID- 16584761
TI  - Extraperitoneal laparoscopic ureterolithotomy in the supine position for impacted
      ureteral stones.
AB  - We describe initial experiences with extraperitoneal laparoscopic
      ureterolithotomy in the supine position. This method can provide adequate working
      space without the risk of mechanical bowel injury and nerve stretching specific
      to the flank position.

PMID- 16584760
TI  - A prospective evaluation of rectal bleeding after dose-escalated three
      dimensional conformal radiation therapy using an intrarectal balloon for prostate
      gland localization and immobilization.
AB  - OBJECTIVES: To estimate the rates of rectal bleeding after dose-escalated three
      dimensional conformal radiation therapy (3D-CRT) on a prospective, Phase II study
      in which a modified intrarectal balloon was used for prostate gland localization
      and immobilization. METHODS: The study cohort comprised 100 men with biopsy
      proven adenocarcinoma of the prostate and at least one high-risk feature
      (prostate-specific antigen level greater than 10 ng/mL, Gleason score 7 or
      higher, or clinical or radiographic T3 disease). Treatment consisted of androgen
      suppression therapy and four-field 3D-CRT with an intrarectal balloon for the
      initial 15 treatments. Planning treatment volume dose was 75.6 Gy. The primary
      endpoint of time to grade 3 rectal bleeding was estimated with the Kaplan-Meier
      method for 57 men with a minimum follow-up of 1 year. RESULTS: For 57 men with a
      median (range) follow-up of 1.8 (1.0 to 3.3) years, the median (range) volume of
      rectum exceeding 70 Gy was 3.7 (0.6 to 14.7) cm3, and the 2-year estimate of
      grade 3 rectal bleeding rate was 10%. This rate was 100% as compared with 0 (P <
      0.0001) for men who were taking warfarin (n = 3) or high-dose aspirin (n = 1) as
      compared with neither, respectively. All grade 3 rectal bleeding events were
      controlled with argon plasma coagulation. CONCLUSIONS: Dose-escalated 3D-CRT with
      an intrarectal balloon technique for prostate localization and immobilization
      produced no measurable grade 3 rectal bleeding unless the patient was taking
      anticoagulants.

PMID- 16584762
TI  - Biochemical disease-free survival in men younger than 60 years with prostate
      cancer treated with radical prostatectomy.
AB  - OBJECTIVES: To determine the biochemical disease-free survival rates in patients
      60 years old or younger who were treated with surgery for localized prostate
      cancer. METHODS: We reviewed the medical records of 291 patients 60 years old or
      younger who had undergone radical prostatectomy as the sole primary treatment for
      prostate cancer. Follow-up prostate-specific antigen (PSA) levels were measured 6
      to 8 weeks after surgery and 4 to 6 months thereafter. Biochemical failure was
      defined as a detectable PSA level (greater than 0.01 ng/mL). The median follow-up
      of the entire study group was 50 months. RESULTS: Eighty-one percent of the
      patients presented with a serum PSA level of 10 ng/mL or less, and 52% had a
      Gleason score of less than 7 on prostate biopsy. The radical prostatectomy
      specimens showed organ-confined disease in 72% of patients, and 83% of tumors had
      a Gleason score of 7. The 1, 5, and 7-year biochemical disease-free survival rate
      was 99%, 91%, and 91%, respectively. The fitted multivariate Cox proportional
      hazards model showed that having a prostatectomy specimen Gleason score greater
      than 7 or seminal vesicle invasion or nodal disease significantly increased the
      risk of biochemical failure. CONCLUSIONS: In the PSA era, men with prostate
      cancer who are 60 years old or younger and treated with surgery have an excellent
      biochemical disease-free outcome.

PMID- 16584763
TI  - Morbidity and efficacy of genitofemoral nerve grafts with radical retropubic
      prostatectomy.
AB  - OBJECTIVES: To review our experience with genitofemoral nerve grafting after
      radical prostatectomy, to determine both morbidity and efficacy. METHODS: We
      identified patients who underwent genitofemoral nerve grafting between 2001 and
      2003 at our hospital. Morbidity was recorded prospectively in the charts, and a
      validated questionnaire (International Index of Erectile Function, IIEF-5) was
      used to determine erectile function. RESULTS: Twenty-seven patients received 32
      genitofemoral nerve grafts. Five patients (19%) received bilateral grafts. In 3,
      a single nerve was harvested for a bilateral graft. Mean graft length was 5 cm,
      and mean follow-up was 14 months. Two patients (7%) reported persistent, minor
      numbness or tingling of the ipsilateral thigh or hemiscrotum. No other morbidity
      was noted. Overall, 56% of the patients were able to sustain an erection with
      enough firmness for penetration at the time of follow-up. Of those patients who
      reported no preoperative erectile dysfunction, 69% were able to have sexual
      intercourse. CONCLUSIONS: Harvesting and interposition of genitofemoral nerve
      grafts in the neurovascular bundle adds very minimal morbidity to radical
      prostatectomy. The results reported in our patients are at least comparable to
      those achieved with sural nerve grafting. Whether these results are a consequence
      of an effective unilateral nerve-sparing dissection or the nerve grafting itself
      is uncertain.

PMID- 16584764
TI  - Influence of leptospirosis on reproductive performance of sows in Brazil.
AB  - The purpose of this study was to investigate the association between
      seropositivity for the most frequent Leptospira serovars and reproductive losses
      in sows in Brazil. Serum samples from 351 sows from 18 herds (in the state of Rio
      de Janeiro, Brazil) with low reproductive efficiency were tested (microscopic
      agglutination) for antibodies against serovars of Leptospira. Antibodies were
      detected in serum samples of 66.1% of all sows, most frequently serovar
      icterohaemorrhagiae (43.1%), followed by pomona (18.1%) and tarassovi (9.9%).
      Seroreactivity to icterohaemorrhagiae and pomona were associated (P<0.05) with
      impaired reproductive performance (and substantial economic loss). Seroreactivity
      for pomona was associated (P<0.05) with stillborn piglets and mummified fetuses,
      whereas seroreactivity to icterohaemorrhagiae was associated (P<0.05) with the
      number of piglets born dead.

PMID- 16584765
TI  - Early pregnancy diagnosis by transrectal ultrasonography in dairy cattle.
AB  - The objective of the present study was to determine differences in time of
      detection of pregnancy between heifers and cows and the interval after
      insemination at which the maximum sensitivity and negative predictive value of
      transrectal ultrasonography were obtained. One-thousand-four-hundred transrectal
      ultrasonographies (TRUS-1; 1,079 in cows and 321 in heifers) were performed using
      a 5-MHz linear-array transducer. The cattle were randomly assigned to have TRUS
      performed once between days 24 and 30 (estrus=day 0) in cows or between days 21
      and 27 in heifers. Every TRUS diagnosis was subsequently compared with a second
      TRUS diagnosis (TRUS-2), performed 3-8 days later, after day 30 (range 31-38) for
      cows and after day 27 (range 28-35) for heifers. The sensitivity and specificity
      between cows and heifers for the common days of TRUS (from 24 to 27) were
      compared. In cows, sensitivity increased gradually from 74.5% at day 24 to 100%
      at day 29 (P<0.01). Specificity increased from days 24-25 and reached a plateau
      of 96.6% on day 26 (P<0.01). In heifers, sensitivity increased from 50% at day 21
      to 100% at day 26 (P<0.01). Specificity increased from 87.5% at day 21 and
      remained steady at 94% starting on day 23 (P>0.05). The sensitivity for cows and
      heifers was 89.2 and 96.8%, respectively (P<0.05) and the specificity was 93.0
      and 93.4% (P>0.05). In this study, heifers were diagnosed pregnant earlier than
      cows, and the maximum sensitivity and negative predictive value were obtained 3
      days earlier in heifers than cows (days 26 and 29, respectively).

PMID- 16584766
TI  - The knobbed acrosome defect in four closely related dogs.
AB  - The knobbed acrosome defect (KAD) has only once been reported in dog sperm. This
      report describes the breeding history, clinical presentation and semen evaluation
      of four closely related miniature Schnauzer dogs that had between 8 and 44% sperm
      with KAD. Two of the dogs had no substantial reproductive or sperm defects other
      than the KAD and were of normal fertility.

PMID- 16584767
TI  - Canine corpus luteum regression: apoptosis and caspase-3 activity.
AB  - The present study evaluated the occurrence of apoptosis and caspase-3 activity in
      the canine corpus luteum during the period of luteal regression in eight pregnant
      and nine nonpregnant diestrus bitches. Intact luteal cells were obtained from
      corpora lutea in both peripartum pregnant bitches and nonpregnant diestrus
      bitches at approximately 65 d (range 63-68) after estrus, but not at days 75 and
      85 in nonpregnant bitches. In all bitches, apoptotic cells were rarely detected
      and when present, those cells were more easily detected using the hematoxylin and
      eosin technique than using the critical electrolyte concentration technique. The
      luteal structures at 75 and 85 d of diestrus had histological characteristics
      similar to a corpus albicans. Caspase-3 activity was detected in morphologically
      normal corpora lutea from both pregnant and diestrus bitches around day 65, and
      also in the later structures considered corpus albicans tissue. These results
      suggested that apoptosis may not be the major mechanism involved in canine
      functional luteal regression, and that caspase-3 participated in both functional
      and morphological luteolysis and in the tissue reorganization involved in corpus
      albicans formation.

PMID- 16584768
TI  - Effect of brine discharge from a desalination plant on macrobenthic communities
      in the NW Mediterranean.
AB  - This paper examines the possible effects of discharges from a desalination plant
      on the macrobenthic community inhabiting the sandy substratum off the coast of
      Blanes in Spain (NW Mediterranean) using multivariate and univariate analyses.
      Two controls and one putatively impacted location were selected and visual
      censuses were carried out 12 times before and 12 times after the plant had begun
      operating. No significant variations attributable to the brine discharges from
      the desalination plant were found. The failure to record any impact may be
      explained by the high natural variability that is a characteristic feature of
      bottoms of this type and also by the rapid dilution undergone by the hypersaline
      brine upon leaving the discharge pipe.

PMID- 16584769
TI  - Self-assembled supramolecular hydrogels formed by biodegradable PEO-PHB-PEO
      triblock copolymers and alpha-cyclodextrin for controlled drug delivery.
AB  - A materials design of a new supramolecular hydrogel self-assembled between alpha
      cyclodextrin and a biodegradable poly(ethylene oxide)-poly[(r)-3-hydroxybutyrate]
      poly(ethylene oxide) (PEO-PHB-PEO) triblock copolymer was demonstrated. The
      cooperation effect of complexation of PEO segments with alpha-cyclodextrin and
      the hydrophobic interaction between PHB blocks resulted in the formation of the
      supramolecular hydrogel with a strong macromolecular network. The in vitro
      release kinetics studies of fluorescein isothiocyanate labeled dextran (dextran
      FITC) model drug from the hydrogel showed that the hydrogel was suitable for
      relatively long-term sustained controlled release of macromolecular drugs, which
      many simple triblock copolymer hydrogel systems could not achieve. The hydrogel
      was found to be thixotropic and reversible, and can be applied as a promising
      injectable drug delivery system.

PMID- 16584770
TI  - Nanofibrous poly(acrylonitrile-co-maleic acid) membranes functionalized with
      gelatin and chitosan for lipase immobilization.
AB  - Nanofibrous membranes with an average diameter of 100 and 180 nm were fabricated
      from poly(acrylonitrile-co-maleic acid) (PANCMA) by the electrospinning process.
      These nanofibrous membranes contain reactive groups which can be used to
      covalently immobilize biomacromolecules. Two natural macromolecules, chitosan and
      gelatin, were tethered on these nanofibrous membranes to fabricate dual-layer
      biomimetic supports for enzyme immobilization in the presence of 1-ethyl-3
      (dimethyl-aminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxyl succinimide
      (NHS). Lipase from Candida rugosa was then immobilized on these dual-layer
      biomimetic supports using glutaraldehyde (GA), and on the nascent PANCMA fibrous
      membrane using EDC/NHS as coupling agent, respectively. The properties of the
      immobilized lipases were assayed. It was found that there is an increase of the
      activity retention of the immobilized lipase on the chitosan-modified nanofibrous
      membrane (45.6+/-1.8%) and on the gelatin-modified one (49.7+/-1.8%), compared to
      that on the nascent one (37.6+/-1.8%). The kinetic parameters of the free and
      immobilized lipases, K(m) and V(max), were also assayed. In comparison with the
      immobilized lipase on the nascent nanofibrous membrane, there is an increase of
      the V(max) value for the immobilized lipases on the chitosan- and gelatin
      modified nanofibrous membranes. Results also indicate that the pH and thermal
      stabilities of lipases increase upon immobilization. The residual activities of
      the immobilized lipases are 55% on the chitosan-modified nanofibrous membrane and
      60% on the gelatin-modified one, after 10 uses.

PMID- 16584771
TI  - Framework for optimal design of porous scaffold microstructure by computational
      simulation of bone regeneration.
AB  - In bone tissue engineering using a biodegradable scaffold, geometry of the porous
      scaffold microstructure is a key factor for controlling mechanical function of
      the bone-scaffold system in the regeneration process as well as after the
      regeneration. In this study, we propose a framework for the optimal design of the
      porous scaffold microstructure by three-dimensional computational simulation of
      bone tissue regeneration that consists of scaffold degradation and new bone
      formation. The rate of scaffold degradation due to hydrolysis, that leads to
      decrease in mechanical properties, was simply assumed to relate to the water
      content diffused from the surface to the bulk material. For the new bone
      formation on both bone and scaffold surfaces, the rate equation of trabecular
      surface remodeling driven by mechanical stimulation was applied. Solving these
      two phenomena in the same time frame, the bone regeneration process in the bone
      scaffold system was predicted by computational simulation using a voxel finite
      element method. The change in the mechanical function of the bone-scaffold system
      during the regeneration process was quantitatively evaluated by measuring the
      change in total strain energy, and this was used for the evaluation function to
      optimize the scaffold microstructure that provides the desired mechanical
      function during and after the bone regeneration process. A case study conducted
      for the scaffold with a simple microstructure demonstrated that the proposed
      simulation method could be applied to the design of a porous scaffold
      microstructure. In addition, the regeneration process was found to be very
      complex even though the simple rate equations for scaffold regeneration and new
      bone formation were used because of the coupling effects of these phenomena.

PMID- 16584772
TI  - Human chorionic gonadotropin expression in human trophoblasts from early
      placenta: comparative study between villous and extravillous trophoblastic cells.
AB  - Human trophoblast differentiates into two pathways: extravillous cytotrophoblasts
      (EVCT) that invade the uterus wall and villous cytotrophoblasts (VCT) that fuse
      to form the syncytiotrophoblast (ST) involved in placental exchanges and
      endocrine function. It is established that hCG is produced and secreted by the ST
      into the maternal compartment where it plays a key endocrine role and stimulates
      ST formation in an autocrine manner. Herein, we investigated hCG expression in
      early placentas by immunohistochemistry using different antibodies. We then
      compared hCG secretion by primary cultures of VCT and EVCT isolated from the same
      first trimester human chorionic villi. In situ hCG was immunodetected in EVCT all
      along their invasive differentiating pathway except in cells near the stromal
      core of the proximal column. hCG expression was confirmed in vitro by
      immunocytochemistry and hCG secretion quantified in cell supernatants.
      Interestingly, whereas hCG secretion increased during VCT differentiation into ST
      (from 60 to 350UI/L/microg DNA), EVCT secretion remained constant and at a high
      level during the same culture period (160UI/L/microg DNA). Our data demonstrated
      that in addition to the ST, invasive EVCT also expressed and secreted high levels
      of hCG, suggesting a specific paracrine and/or autocrine role for hCG from EVCT
      origin.

PMID- 16584773
TI  - Hypoxia regulates the expression of PHLDA2 in primary term human trophoblasts.
AB  - Hypoxia influences gene expression in placental trophoblasts. We sought to
      examine the effect of hypoxia on trophoblast expression of human PHLDA2 (also
      termed IPL, TSSC3 or BWR-1C), a product of an imprinted gene on human chromosome
      11p15.5 whose murine ortholog plays a pivotal role in placental development. We
      initially confirmed that PHLDA2 was expressed in term placental villi, primarily
      in the trophoblast layer. Using quantitative PCR we found that the expression of
      PHLDA2 gradually declined during differentiation of primary term human
      trophoblasts. A similar expression pattern was seen for p57(Kip2) and IGF-II,
      both products of imprinted genes on chromosome 11p15.5. Exposure of trophoblasts
      to hypoxia in vitro (O(2)<or=2%) markedly reduced the expression of PHLDA2 mRNA
      and protein. This effect was not consistent among other chromosome 11p15.5 genes
      products, as the expression of p57(Kip2) decreased, but that of IGF-II increased
      in hypoxic trophoblasts. PHLDA2 expression in trophoblasts exposed to TGFbeta1, 
      beta2 or -beta3 was unchanged. We conclude that hypoxia down-regulates the
      expression of PHLDA2 in human term placental trophoblasts. As murine PHLDA2
      limits placental growth, our results suggest that down-regulation of PHLDA2
      attenuates the impact of hypoxia on placental growth.

PMID- 16584774
TI  - Loss of a gimap/ian gene leads to activation of NF-kappaB through a MAPK
      dependent pathway.
AB  - The diabetes-prone biobreeding (BB-DP) rat contains the lyp mutation which
      results in lymphopenia and promotes the progression of a T cell-mediated
      autoimmune attack of the pancreas in certain rat strains. This mutation has been
      mapped to a gene which bears homology to human Gimap5/Ian5 and results in the
      truncation and loss of activity of this protein. The lymphopenic state induced by
      the loss of this protein has led to the proposal that Gimap5 has an anti
      apoptotic function. Previously we described an additional phenotype of incomplete
      activation mediated by the loss of Gimap5 function. Here we further characterize
      this incomplete activation phenotype and map a potential signal transduction
      pathway leading to activation. We show that CD5 expression on peripheral T cells
      is elevated in Gimap5 animals, while thymocyte expression remains similar between
      the two strains. Additionally, we show that NF-kappaB but not NFAT is activated
      in unstimulated Gimap5 mutant T cells as compared to unstimulated wild type T
      cells. Mapping this activation to its upstream source we show that activation of
      NF-kappaB is correlated with an activation of IKK. Using a variety of kinase
      inhibitors we further map this increase in IKK to an increase in MEK activation.
      Finally, to counter the possibility that activation is an indirect consequence of
      the lymphopenic environment, we created bone marrow chimeras in which Gimap5
      mutant T cells developed in a normal environment and show that these cells retain
      their activated phenotype. Together, we interpret these data as demonstrating
      that the activation caused by loss of Gimap5 is a cell intrinsic phenomenon
      caused, in part, by a MEK-dependent activation of IKK. This, in turn, would
      suggest that Gimap5 functions to promote both T cell survival and quiescence and
      that these pathways are biochemically linked.

PMID- 16584775
TI  - Identification of a regulatory cis-element within the 3'-untranslated region of
      the murine inducible nitric oxide synthase (iNOS) mRNA; interaction with
      heterogeneous nuclear ribonucleoproteins I and L and role in the iNOS gene
      expression.
AB  - The aim of this study was to investigate the role of heterogeneous nuclear
      ribonucleoprotein I (hnRNPI) and hnRNPL in the regulation of the murine inducible
      nitric oxide synthase (iNOS) gene during inflammation. Treatment of mice with
      lipopolysaccharide (LPS)/D-galactosamine, or of RAW 264.7 cells with
      LPS/interferon-gamma (IFN-gamma), strongly increased iNOS expression while
      reducing hnRNPI levels and complex formation between hnRNPI/hnRNPL and the 3'
      untranslated region (3'-UTR) of iNOS mRNA. Introduction of the iNOS 3'-UTR to a
      luciferase reporter gene reduced its expression in RAW 264.7 cells. However, when
      hnRNPI and hnRNPL binding sites were deleted, luciferase expression was
      recovered. LPS/IFN-gamma increased the luciferase activity of the full-length 3'
      UTR construct compared to control, while its effects on the deletion constructs
      were modest. The results indicate that LPS/IFN-gamma induce iNOS through a
      mechanism involving hnRNPI and hnRNPL binding to iNOS 3'-UTR. Our data suggest
      that iNOS mRNA degradation is promoted upon binding of hnRNPI and hnRNPL to a
      destabilizing region within its 3'-UTR, while inflammatory stimuli causing
      dissociation of the mRNA-protein complex, yield a more stable transcript. This
      appears to be particularly significant during extended inflammatory stimuli,
      resulting in sustained nitric oxide production. The critical event launching this
      process appears to be the degradation of hnRNPI.

PMID- 16584777
TI  - Neuropsychological health in F-111 aircraft maintenance workers.
AB  - OBJECTIVE: To contrast subjective and objective measures of neuropsychological
      health in F-111 aircraft Deseal/Reseal maintenance personnel, against two
      appropriate comparison groups. METHODS: Exposed and comparison participants
      completed a postal questionnaire which included a validated memory questionnaire
      and additional questions relating to possible cognitive symptoms. They also
      underwent a comprehensive neuropsychological assessment and screening for a past
      or current disturbance of mood. Multiple linear or logistic regression was
      conducted for each outcome using exposure group and potential confounders as
      explanatory variables. RESULTS: There was a strong and consistent excess of self
      reported cognitive problems among the exposed group relative to the comparison
      groups including a 2.8-4.3-fold increase in self-reported symptoms of
      forgetfulness, loss of concentration and difficulty finding the right word. On
      detailed neuropsychological testing, the exposed group performed significantly
      worse than comparisons on tests of psychomotor speed, executive functioning, and
      new learning/memory. These findings could not be accounted for by disturbances of
      mood or other potential confounders. CONCLUSIONS: There was a strong and
      consistent increase in self-reported cognitive problems among the exposed, and
      small but significant exposure-specific differences on objective tests of
      cognitive functioning. The findings are consistent with the development of
      adverse neuropsychiatric changes related to occupational exposure to solvents.

PMID- 16584776
TI  - Cigarette tar phenols impede T cell cycle progression by inhibiting cyclin
      dependent kinases.
AB  - Cigarette smoking causes profound suppression of pulmonary T cell responses,
      which is associated with increased susceptibility to respiratory tract infections
      and decreased tumor surveillance. We previously demonstrated that the phenolic
      compounds in cigarette tar inhibit blastogenesis and interfere with human T cell
      cycle progression. To identify the mechanism by which cell cycle arrest occurs,
      we examined the effects of these compounds on cyclin-dependent kinases (Cdk) that
      control the G0/G1 transition. We found that hydroquinone inhibited induction of
      Cdk4 and Cdk6 kinase activities by >80%, while catechol and phenol were markedly
      less potent. HQ did not affect mitogenic induction of the Cdk6 protein, but
      inhibited expression of cyclin D3 by >90% resulting in a dramatic reduction in
      proper Cdk6/Cyclin D3 complex formation.

PMID- 16584778
TI  - Production and characterization of a polyclonal antibody for Os(II) and Ru(II)
      polypyridyl complexes.
AB  - The characterization of a polyclonal antibody produced via immunization with an
      [Os(bpy)(2)dcbpy] hapten is described. Bpy is 2,2'-bipyridine and dcbpy is 2,2'
      bipyridine-4,4'-dicarboxylic acid. The cross-reactivity of the antibody for the
      Ru(II) analogue of the hapten was also investigated. Large increases in the
      emission and luminescent lifetime of a series of Os and Ru complexes were
      observed on binding of the antibody. Association equilibrium constants were
      derived from luminescence titration data and were found to be 5.6 x 10(8) and 5.0
      x 10(8)M(-1) for [Os(bpy)(2)dcbpy] and [Ru(bpy)(2)dcbpy], respectively.
      Spectroscopic changes were likely due to the exclusion of H(2)O from the
      complex/antibody binding cleft and blocking of vibrational relaxation pathways of
      the Os/Ru excited state. D(2)O/H(2)O experiments confirmed that the antibody
      protected approx. 82% of [Os(bpy)(2)dcbpy] and 80% of [Ru(bpy)(2)dcbpy] from
      excited state deactivation by the aqueous solvent.

PMID- 16584779
TI  - Copper complexes with heterocyclic sulfonamides: synthesis, spectroscopic
      characterization, microbiological and SOD-like activities: crystal structure of
      [Cu(sulfisoxazole)2(H2O)4] . 2H2O.
AB  - The synthesis, characterization and comparative biological study of a series of
      antibacterial copper complexes with heterocyclic sulfonamides were reported. Two
      kinds of complexes were obtained with the stoichiometries [Cu(L)2] . H2O and
      [Cu(L)2(H2O)4] . nH2O. They were characterized by infrared and electronic
      spectroscopies and the crystal structure of [Cu(sulfisoxazole)2(H2O)4] . 2H2O was
      determined by single crystal X-ray diffraction. It crystallized in the C2/c with
      Z = 8 monoclinic space group C2/c with Z = 8. The Cu(II) is in a slightly
      tetragonal distorted octahedron formed by four oxygen atoms from water molecules
      and two nitrogen atoms from two isoxazole rings. The antimicrobial activity was
      evaluated for all the synthesized complexes and ligands using the agar dilution
      test. The results showed that the complexes with five-membered heterocyclic rings
      were more active than the free sulfonamides while the pyrimidine, pyridine and
      pyridazine complexes had similar or less activity than the free ligands. In order
      to find an explanation for this behavior lipophilicity and superoxide dismutase
      like activity were tested, showing that the [Cu(sulfamethoxazol)2(H2O)4] . 3H2O
      presented the highest antimicrobial potency and a superoxide dismutase-like
      activity comparable with pharmacological active compounds.

PMID- 16584780
TI  - Hydroxide instead of bicarbonate in the structure of the oxygen evolving complex.
AB  - The energy diagram for the catalytic cycle of dioxygen evolution in photosystem
      II has been recomputed using a slightly different model than the one used
      previously, since the results showed an erroneous trend in the critical region
      from S(2) to S(3). By replacing the bicarbonate ligand, which was bridging
      between calcium and the outer manganese, by a hydroxide a significant improvement
      of the energy diagram is obtained. Most notably, the S(2) to S(3) transition is
      now exergonic as it should be. However, for the S(2)(0) state an artificial
      constraint is needed on the hydrogen bonding, indicating that there is still some
      problem with the model used. This hydroxide model was used to study the effects
      of replacing calcium with strontium, magnesium and cadmium. The computed results
      reproduce the results observed experimentally that magnesium and cadmium suppress
      water oxidation and that strontium slows it down. For both magnesium and cadmium
      the process stops already at S(2).

PMID- 16584781
TI  - A functional model for pMMO (particulate methane monooxygenase): Hydroxylation of
      alkanes with H2O2 catalyzed by beta-diketiminatocopper(II) complexes.
AB  - The reaction of copper(II) complexes supported by a series of beta-diketiminate
      ligands ((R1,R2)L, [(Dipp)N-C(R(2))-C(R(1))-C(R(2))-N(Dipp)](-), Dipp=2,6
      diisopropylphenyl; see ) and H(2)O(2) has been examined spectroscopically at a
      low temperature. The beta-diketiminatocopper(II) complexes with R(2)=H (no
      substituent on the beta-carbon) provided a copper-oxygen intermediate that
      exhibited the same spectroscopic features as those of the bis(mu
      oxo)dicopper(III) complex generated by the reaction of corresponding beta
      diketiminatocopper(I) complex and O(2). On the other hand, the beta
      diketiminatocopper(II) complexes with methyl substituent on the beta-carbon
      (R(2)=Me) did not produce such an intermediate in the same reaction. The beta
      diketiminatocopper(II) complexes carrying an electron-withdrawing substituent on
      the alpha-carbon (R(1)=NO(2) or CN) but no beta-substituent (R(2)=H) exhibited a
      high catalytic activity in the oxygenation reaction of alkanes with H(2)O(2).
      Mechanism of the catalytic oxygenation reaction as well as the substituent
      effects of the ligands on the copper(II)-H(2)O(2) reactivity is discussed.

PMID- 16584782
TI  - Bridging-type changes facilitate successive oxidation steps at about 1 V in two
      binuclear manganese complexes--implications for photosynthetic water-oxidation.
AB  - The redox behavior of two synthetic manganese complexes illustrates a mechanistic
      aspect of importance for light-driven water oxidation in Photosystem II (PSII)
      and design of biomimetic systems (artificial photosynthesis). The coupling
      between changes in oxidation state and structural changes was investigated for
      two binuclear manganese complexes (1 and 2), which differ in the set of first
      sphere ligands to Mn (N(3)O(3) in 1, N(2)O(4) in 2). Both complexes were studied
      by electron paramagnetic resonance (EPR) and X-ray absorption spectroscopy (XAS)
      in three oxidation states which had been previously prepared either electro- or
      photochemically. The following bridging-type changes are suggested. In 1: Mn(II)
      (mu-OR)(mu-OCO)(2)-Mn(II)<-->Mn(II)-(mu-OR)(mu-OCO)(2)-Mn(III)-->Mn(III)-(mu
      OR)(mu-OCO)(mu-O)-Mn(III). In 2: Mn(II)-(mu-OR)(mu-OCO)(2)-Mn(III)<-->Mn(III)-(mu
      OR)(mu-OCO)(2)-Mn(III)-->Mn(III)-(mu-OR)(mu-OCO)(mu-O)-Mn(IV). In both complexes,
      the first one-electron oxidation proceeds without bridging-type change, but
      involves a redox-potential increase by 0.5-1V. The second one-electron oxidation
      likely is coupled to mu-oxo-bridge (or mu-OH) formation which seems to counteract
      a further potential increase. In both complexes, mu-O(H) bridge formation is
      associated with a redox transition proceeding at approximately 1V, but the mu
      O(H) bridge is observed at the Mn(2)(III,III) level in 1 and at the Mn(III,IV)
      level in 2, demonstrating modulation of the redox behavior by the terminal
      ligands. It is proposed that also in PSII bridging-type changes facilitate
      successive oxidation steps at approximately the same potential.

PMID- 16584783
TI  - Successful treatment of disseminated Fusariosis after allogeneic hematopoietic
      stem cell transplantation with the combination of voriconazole and liposomal
      amphotericin B.
AB  - Fusarium is an opportunistic fungal pathogen which is emerging as a significant
      cause of morbidity and mortality in the immunocompromised host [Fleming RV, Walsh
      TJ, Anaissie EJ. Emerging and less common fungal pathogens. Infect Dis Clin North
      Am 2002;16:915-34]. This disease can be localized, focally invasive or
      disseminated, when two or more noncontiguous sites are involved. Therapeutic
      options are scarce and mortality reaches 80-90% in patients subjected to
      allogeneic hematopoietic stem cell transplant (allo-SCT) [Nucci M, Marr KA,
      Queiroz-Telles F, Martins CA, Trabasso P, Costa S, et al. Fusarium infection in
      hematopoietic stem cell transplant recipient. Clin Infect Dis 2004;1237-42]. We
      report a case of disseminated Fusariosis in a severe immunocompromised patient
      after allo-SCT that responded to treatment with the early combination of
      intravenous voriconazole and liposomal amphotericin B.

PMID- 16584785
TI  - Pott's disease occurring after percutaneous vertebroplasty: an unusual
      illustration of the principle of locus minoris resistentiae.
AB  - We report an unusual case of a multifocal tuberculous spondylitis that has been
      diagnosed after several percutaneous vertebroplasty. This event supports the
      theory that surgical or radiological intervention such as a percutaneous
      vertebroplasty should be considered as an intentional traumatism that can lead to
      the initiation of a locus minoris resistentiae, probably by reactivating an
      inactive tuberculous lesion.

PMID- 16584786
TI  - Receptor-independent actions of cannabinoids on cell membranes: focus on
      endocannabinoids.
AB  - Cannabinoids are a structurally diverse group of mostly lipophilic molecules that
      bind to cannabinoid receptors. In fact, endogenous cannabinoids
      (endocannabinoids) are a class of signaling lipids consisting of amides and
      esters of long-chain polyunsaturated fatty acids. They are synthesized from lipid
      precursors in plasma membranes via Ca(2+) or G-protein-dependent processes and
      exhibit cannabinoid-like actions by binding to cannabinoid receptors. However,
      endocannabinoids can produce effects that are not mediated by these receptors. In
      pharmacologically relevant concentrations, endocannabinoids modulate the
      functional properties of voltage-gated ion channels including Ca(2+) channels,
      Na(+) channels, various types of K(+) channels, and ligand-gated ion channels
      such as serotonin type 3, nicotinic acetylcholine, and glycine receptors. In
      addition, modulatory effects of endocannabinoids on other ion-transporting
      membrane proteins such as transient potential receptor-class channels, gap
      junctions and transporters for neurotransmitters have also been demonstrated.
      Furthermore, functional properties of G-protein-coupled receptors for different
      types of neurotransmitters and neuropeptides are altered by direct actions of
      endocannabinoids. Although the mechanisms of these effects are currently not
      clear, it is likely that these direct actions of endocannabinoids are due to
      their lipophilic structures. These findings indicate that additional molecular
      targets for endocannabinoids exist and that these targets may represent novel
      sites for cannabinoids to alter either the excitability of the neurons or the
      response of the neuronal systems. This review focuses on the results of recent
      studies indicating that beyond their receptor-mediated effects, endocannabinoids
      alter the functions of ion channels and other integral membrane proteins
      directly.

PMID- 16584787
TI  - Measuring spike pattern reliability with the Lempel-Ziv-distance.
AB  - Spike train distance measures serve two purposes: to measure neuronal firing
      reliability, and to provide a metric with which spike trains can be classified.
      We introduce a novel spike train distance based on the Lempel-Ziv complexity that
      does not require the choice of arbitrary analysis parameters, is easy to
      implement, and computationally cheap. We determine firing reliability in vivo by
      calculating the deviation of the mean distance of spike trains obtained from
      multiple presentations of an identical stimulus from a Poisson reference. Using
      both the Lempel-Ziv-distance (LZ-distance) and a distance focussing on coincident
      firing, the pattern and timing reliability of neuronal firing is determined for
      spike data obtained along the visual information processing pathway of macaque
      monkey (LGN, simple and complex cells of V1, and area MT). In combination with
      the sequential superparamagnetic clustering algorithm, we show that the LZ
      distance groups together spike trains with similar but not necessarily
      synchronized firing patterns. For both applications, we show how the LZ-distance
      gives additional insights, as it adds a new perspective on the problem of firing
      reliability determination and allows neuron classifications in cases, where other
      distance measures fail.

PMID- 16584788
TI  - Antigen-specific proliferation and activation of peripheral blood mononuclear
      cells from Mycobacterium bovis-infected reindeer.
AB  - To evaluate antigen-specific proliferative and activation-associated responses
      from Mycobacterium bovis-infected reindeer, blood mononuclear cells from M. bovis
      (n = 10) and non-infected reindeer (n = 4) were stimulated with a recombinant
      early secretory antigenic target-6 and culture filtrate protein-10 fusion protein
      (rESAT6:CFP10), M. bovis purified protein derivative, pokeweed mitogen, or medium
      alone and evaluated by flow cytometry using dye tracker analysis and cell surface
      marker staining. gammadelta TCR+ and CD8+ cells, but not CD4+ cells, from M.
      bovis-infected reindeer proliferated in response to specific antigen stimulation.
      Expression (i.e., mean fluorescence intensity) of CD44 was increased and CD62L
      decreased on proliferative as compared to non-proliferative fractions in antigen-
      and mitogen-stimulated cultures. In response rESAT6:CFP10 stimulation, MHC II
      fluorescence intensity was increased on CD4+, gammadelta TCR+, CD172a+, and IgM+
      cells from infected reindeer as compared to that of non-stimulated cells from the
      same reindeer. Recombinant ESAT6:CFP10 stimulation also induced expansion of a
      CD172a+, MHC II+ population within mononuclear cell cultures from M. bovis
      infected reindeer. Despite a moderate challenge dose and extended duration of
      incubation, experimental infection of reindeer was generally limited to lymph
      nodes draining the inoculation site, suggestive of host resistance to progressive
      disease. Present in vitro findings, therefore, may be predictive of host
      responses by reindeer that limit progression to disseminated disease.

PMID- 16584789
TI  - Mouse follicular and marginal zone B cells show differential expression of Dnmt3a
      and sensitivity to 5'-azacytidine.
AB  - Mature B cells in the spleen of mouse and human comprise of two main subsets, the
      follicular (Fo) B cells and the marginal zone (MZ) B cells. In this study, we
      report that Fo and MZ B cells express different levels of DNA methyltransferase
      Dnmt3a. By using RT-PCR and immunohistochemistry, we found that Fo B cells
      expressed high level of Dnmt3a while MZ B cells expressed little. Treatment of
      mice by in vivo administration of 5'-azacytidine, an inhibitor of DNA
      methyltransferases, induced B cell loss in both the bone marrow and the spleen.
      We noticed that this treatment resulted in a much faster and more severe
      disappearance of Fo B cells than MZ B cells in the spleen. Further analysis
      showed that MZ progenitors increased significantly in mice treated with 5'
      azacytidine. These results suggest that epigenetic mechanisms involving Dnmt3a
      might participate in the development of B cells including the differentiation of
      Fo B cells and MZ B cells in the periphery.

PMID- 16584790
TI  - The hypothalamic H1 receptor: a novel therapeutic target for disrupting diurnal
      feeding rhythm and obesity.
AB  - Histamine-containing neurons and histamine H1 receptors are distributed within
      the brain and peripheral tissues. The results of physiological and
      pharmacological studies have revealed that brain histamine and H1 receptors are
      involved in the regulation of feeding and obesity in rodents. The adipocytokine
      leptin regulates feeding and obesity, partially through brain histamine.
      Furthermore, recent studies have provided evidence that regulation of the diurnal
      rhythm of feeding through H1 receptors is a crucial factor in the development of
      obesity. Thus, the regulation of H1 receptors is important for the control of
      energy metabolism, feeding rhythms and obesity in rodents.

PMID- 16584791
TI  - Corticosteroid effects in the brain: U-shape it.
AB  - The existence of U-shaped dose dependencies has been known for a long time. With
      regard to corticosteroid action in brain cells, a dual receptor system that works
      in opposing directions can explain the occurrence of a U-shaped dose dependency.
      However, recent evidence indicates that many cell- and tissue-specific factors
      (e.g. the local availability of corticosterone, the expression of receptor
      variants and the cellular content of other proteins and molecules) also determine
      the effectiveness of the hormone. This could result in dose dependencies with a
      different shape, despite the local presence of two receptor types.

PMID- 16584792
TI  - Novel, rapid assay for measuring entry of diverse enveloped viruses, including
      HIV and rabies.
AB  - Entry is the first and essential step in virus replication and is a target for
      therapeutic intervention. However, current knowledge on entry mechanism for the
      majority of viruses is poor, partly due to lack of a simple, sensitive and
      accurate entry assay that can be applied to diverse viruses. To overcome this
      obstacle, a novel contents-mixing-based virus entry assay is described that can
      be broadly applied to many enveloped viruses. By fusing firefly luciferase to the
      HIV Nef protein, luciferase was directly packaged into HIV particles pseudotyped
      with envelope proteins of diverse viruses including HIV, rabies and others. Upon
      cell entry, the luciferase-fusion protein was released into the cell cytoplasm,
      reacted with its substrates and was detected by light emission. The assay was
      validated by demonstrating its versatility in measuring virus entry. Entry was
      detected much more rapidly (in real-time) with higher sensitivity (a multiplicity
      of infection <0.1 gives a robust signal) and lower background (signal/noise
      ration >1000) than other comparable assays. In addition to its utility in
      studying virus entry mechanisms, the assay will aid in screening potential
      entry/fusion inhibitors and in diagnosis of virus infections.

PMID- 16584793
TI  - Incentive-compatible guaranteed renewable health insurance premiums.
AB  - Theoretical models of guaranteed renewable insurance display front-loaded premium
      schedules. Such schedules both cover lifetime total claims of low-risk and high
      risk individuals and provide an incentive for those who remain low-risk to
      continue to purchase the policy. Questions have been raised of whether actual
      individual insurance markets in the US approximate the behavior predicted by
      these models, both because young consumers may not be able to "afford" front
      loading and because insurers may behave strategically in ways that erode the
      value of protection against risk reclassification. In this paper, the optimal
      competitive age-based premium schedule for a benchmark guaranteed renewable
      health insurance policy is estimated using medical expenditure data. Several
      factors are shown to reduce the amount of front-loading necessary. Indeed, the
      resulting optimal premium path increases with age. Actual premium paths exhibited
      by purchasers of individual insurance are close to the optimal renewable schedule
      we estimate. Finally, consumer utility associated with the feature is examined.

PMID- 16584794
TI  - Adverse effect of a distended rectum in intensity-modulated radiotherapy (IMRT)
      treatment planning of prostate cancer.
AB  - BACKGROUND AND PURPOSE: The retrospective planning study for intensity-modulated
      radiotherapy (IMRT) of prostate cancer evaluated whether proximal rectum and
      supra-anal rectum/anal canal should be delineated as separated organs-at-risk
      (OARs) to achieve optimal dose distributions to the anorectal region. PATIENTS
      AND METHODS: For 10 patients with localized prostate cancer IMRT plans were
      generated with the rectum and anal canal as separated OARs (Rec-sep) and as one
      single OAR (Rec-tot). Two different treatment planning systems (TPS) were
      utilized. Influence on dose distributions to target and OARs was analyzed.
      RESULTS: Results from both TPS showed significantly increased doses to the distal
      rectum/anal canal for plans Rec-tot compared with Rec-sep in case of a distended
      rectum in the planning CT study: doses were increased by up to mean 31% (P =
      0.02) and 18% (P = 0.03), respectively, in both TPS. For the patient with the
      largest rectum, the maximum dose increase was 61%. No significant differences in
      doses to target, bladder, femoral head and proximal rectum were seen.
      CONCLUSIONS: For patients with a distended rectum in the planning CT, delineation
      of separated OARs for proximal rectum and distal rectum/anal canal resulted in
      superior dose distributions to the anorectal region and therefore, we recommend
      this as standard procedure for IMRT planning of prostate cancer.

PMID- 16584795
TI  - Effects of aging on motor cortex excitability.
AB  - To determine whether aging is associated with changes in excitability of the
      cerebral cortex, we evaluated the excitability of the motor cortex with
      transcranial magnetic stimulation (TMS). We compared TMS related measures
      obtained in a group of young people with those of a group of old people. Motor
      evoked potential (MEP) amplitude was significantly smaller in older than in
      younger controls (1.3+/-0.8 mV versus 2.7+/-1.1 mV; p<0.0071). Mean cortical
      silent period (CSP) duration was shorter in older than in younger controls (87+/
      29 ms versus 147+/-39 ms; p<0.0071). SP duration/MEP amplitude ratios were
      similar in both groups. Our results are consistent with an impaired efficiency of
      some intracortical circuits in old age.

PMID- 16584796
TI  - Accumulation of hEGF and hEGF-fusion proteins in chloroplast-transformed tobacco
      plants is higher in the dark than in the light.
AB  - Chloroplast transformation has many potential advantages for the production of
      recombinant proteins in plants. However, it has been reported that heterologous
      protein accumulation in chloroplasts could be hindered by post-transcriptional
      mechanisms not yet characterized. Here, we describe the development and
      characterization of transplastomic tobacco plants transformed with four different
      transformation vectors for the expression of human epidermal growth factor
      (hEGF). We showed that, although the corresponding transcript was present in all
      of the analyzed plants, hEGF could only be detected when fused to the first 186
      amino acids of bacterial beta-glucuronidase (GUS). In addition, we observed that
      the expression levels of recombinant protein increased when plants were placed in
      the dark or when leaves were incubated in the presence of electron transport
      inhibitors, such as methyl viologen (MV) and 3-(3,4-dichlorophenyl)-1,1
      dimethylurea (DCMU). These results suggest that the mechanism responsible for
      hEGF instability in chloroplasts is regulated by light.

PMID- 16584797
TI  - The feruloyl esterase system of Talaromyces stipitatus: determining the
      hydrolytic and synthetic specificity of TsFaeC.
AB  - The active site of the recombinant Talaromyces stipitatus type-C feruloyl
      esterase (TsFaeC) was probed using a series of C1-C4 alkyl ferulates and methyl
      esters of phenylalkanoic and cinnamic acids. The enzyme was active on 23 of the
      34 substrates tested. Lengthening or shortening the aliphatic side chain while
      maintaining the same aromatic substitutions completely abolished the enzyme
      activity. Maintaining the phenylpropenoate structure but altering the
      substitutions of the aromatic ring demonstrated the importance of hydroxyl groups
      on meta and/or para position of the benzoic ring. The highest catalytic
      efficiency of TsFaeC for methyl cinnamates was shown on methyl 3,4-dihydroxy
      cinnamate and on its hydro form (3,4-dihydroxy-phenyl-propionate). Maintaining
      the ferulate structure but altering the esterified alkyl group, the comparison of
      k(cat) and k(cat)/K(m) values showed that the enzyme hydrolysed faster and more
      efficiently than ethyl ferulate. Alkyl ferulates were applied also for substrate
      selectivity mapping of feruloyl esterase to catalyze feruloyl group transfer to l
      arabinose, using as a reaction system a ternary water-organic mixture consisting
      of n-hexane, t-butanol and water. The reaction parameters affecting the
      feruloylation rate and the conversion of the enzymatic synthesis, such as the
      composition of the reaction media, temperature, substrate and enzyme
      concentration have been investigated.

PMID- 16584798
TI  - Regulation of transduction efficiency by pegylation of baculovirus vector in
      vitro and in vivo.
AB  - In this study, poly(ethylene glycol) (PEG) was coupled to baculovirus to regulate
      transduction efficiency of baculovirus in vitro and in vivo. The degree of
      pegylation in virions was measured by the loss of free amines via a fluorescamine
      based assay. The efficiency of green fluorescent protein (GFP) expression was
      used to monitor transduction efficiency. As the results, the transduction
      efficiency in pegylated baculovirus was decreased with an increase of pegylation
      in baculovirus in vitro and in vivo. Interestingly, the transduction efficiency
      of the pegylated baculovirus for the lung and brain was increased compared with
      baculovirus itself possibly owing to increased stability of baculovirus by
      pegylation.

PMID- 16584799
TI  - Characterization of a metagenome-derived halotolerant cellulase.
AB  - Metagenomes of uncultured microorganisms represent a sheer unlimited resource for
      discovery of novel biocatalysts. Here, we report on the biochemical
      characterisation of a novel, soil metagenome-derived cellulase (endoglucanase),
      Cel5A. The deduced amino acid sequence of Cel5A was similar to a family 5, single
      domain cellulase with no distinct cellulose binding domain from Cellvibrio
      mixtus. The 1092bp ORF encoding Cel5A was overexpressed in Escherichia coli and
      the corresponding 42.1 kDa protein purified using three-step chromatography. The
      recombinant Cel5A protein was highly active against soluble cellulose substrates
      containing beta-1,4 linkages, such as lichenan and barley beta-glucan, and not
      active against insoluble cellulose. Glucose was not among the initial hydrolysis
      products, indicating an endo mode of action. Cel5A displayed a wide range of pH
      activity with a maximum at pH 6.5 and at least 60% activity at pH 5.5 and 9.0.
      The enzyme was highly stable at 40 degrees C for up to 11 days, and retained 86
      87% activity after incubation with 3M NaCl, 3M RbCl or 4M KCl for 20 h. Cel5A was
      also active in the presence of diverse divalent cations, detergents and EDTA.
      This highly stable, salt and pH tolerant cellulase is an ideal candidate for
      industrial applications.

PMID- 16584800
TI  - Elevation of monocyte-derived microparticles in patients with diabetic
      retinopathy.
AB  - Diabetic retinopathy is associated with microvascular damage and capillary
      occlusions which are common features of the microangiopathy in diabetes. Monocyte
      derived microparticles (MDMPs) are released from activated monocytes and enhance
      the procoagulant activity, and also activate adhesion reactions. These are key
      events in the development of capillary occlusion. The MDMPs level in the blood,
      and platelet activation markers (platelet-derived microparticles (PDMPs), CD62P
      and CD63) were measured by flow cytometry in 72 diabetic patients. The plasma
      levels of intracellular adhesion molecule-1 (ICAM-1) and P-selectin were analyzed
      by ELISA. The level of MDMPs was significantly correlated with the levels of
      PDMPs (r=0.52, P<0.001), CD62P (r=0.37, P=0.001), CD63 (r=0.31 and P=0.007), P
      selectin (r=0.38, P=0.001), and ICAM-1 (r=0.31, P=0.009). The MDMPs level
      increased with the progression of the diabetic retinopathy: 81+/
      14/10(4)platelets (plts) in patients without retinopathy (n=10); 88+/-8/10(4)plts
      with mild or moderate non-proliferative diabetic retinopathy (NPDR, n=12); 95+/
      8/10(4)plts with severe NPDR (n=24); and 112+/-9/10(4)plts with proliferative
      diabetic retinopathy (PDR) (n=26). The MDMPs level in patients with areas of
      capillary occlusion (123+/-10/10(4)plts, n=25) was significantly higher than that
      in patients without areas of capillary occlusion (84+/-5/10(4)plts, n=25;
      P=0.0008). These correlations suggest that increased levels of MDMPs may
      accelerate the progression of diabetic retinopathy.

PMID- 16584801
TI  - Psychosocial and non-psychosocial risk factors for the new diagnosis of diabetes
      in elderly women.
AB  - OBJECTIVES: Determine psychosocial variables associated with the new diagnosis of
      diabetes in elderly women. Examine whether variables remained significant
      predictors after controlling for non-psychosocial risk factors and the frequency
      of doctor visits. RESEARCH DESIGN AND METHODS: A longitudinal cohort study was
      conducted using data from 10300 women who completed a survey in 1996 and 1999.
      The women were aged between 70 and 74 years of age in 1996. The were asked to
      provide self-reports on a number of psychosocial and non-psychosocial variables
      in 1996 and on whether they had been diagnosed for the first time with diabetes
      in the 3-year period. The relationships between the potential risk factors and
      new diagnosis of diabetes were examined using binary logistic regression
      analysis. RESULTS: Univariate results showed that not having a current partner,
      having low social support and having a mental health index score in the clinical
      range were all associated with higher risks of being diagnosed with diabetes for
      the first time. However the multivariate results showed that only a mental health
      index score in the clinical range and not having a current partner provided
      unique prediction of being newly diagnosed with diabetes. Of the non-psychosocial
      variables measured, only having a high BMI and hypertension were associated with
      increased risks of new diagnosis, while there was also evidence of a U shaped
      relationship between alcohol consumption and new diagnosis. Even after adjusting
      for frequency of doctor visits and non-psychosocial risk factors, a mental health
      index in the clinical range proved to still be a significant risk factor.
      CONCLUSIONS: A score on the mental health index that is within the clinical range
      is an independent risk factor for the new diagnosis of diabetes in elderly women.

PMID- 16584802
TI  - Six year incidence and progression of diabetic retinopathy: results from the
      Mauritius diabetes complication study.
AB  - AIMS: To determine the incidence, progression and risk factors for diabetic
      retinopathy in the multiethnic population of Mauritius. METHOD: A longitudinal,
      population-based study was conducted in Mauritius, during 1987, 1992 and 1998.
      Participants identified through the study as having diabetes (both known and
      newly diagnosed, by self-report and oral glucose tolerance test) and one in four
      participants with impaired glucose tolerance (IGT) underwent complications
      screening in 1992 and 1998. Retinal photographs were taken using a TRC-50VT
      retinal camera in three fields of the right eye (centred on the optic disc;
      macula (temporal to the optic disc); and nasal to disc). Photographs were graded
      according to a simplified version of the Wisconsin grading system. RESULTS: The 6
      year incidence of diabetic retinopathy was 23.8% (sight-threatening in 0.4%).
      Among those with known diabetes mellitus (KDM) and free of retinopathy at
      baseline the incidence of non-proliferative diabetic retinopathy (NPDR) was 29.2%
      and proliferative diabetic retinopathy (PDR) was 1.0%. Among those with newly
      diagnosed diabetes mellitus (NDM) at baseline the incidence of NPDR was 19.1% (no
      incident cases of PDR were found). Independent risk factors for retinopathy using
      the baseline population characteristics were duration of diabetes and fasting
      plasma glucose. CONCLUSIONS: This is one of the few recent population-based
      studies of diabetic retinopathy undertaken in a developing nation. The incidence
      of retinopathy in Mauritius was high among those with NDM at baseline, with one
      in five developing retinopathy over 6 years. These results support the concept
      that screening for diabetes is important.

PMID- 16584803
TI  - Progressivity and horizontal equity in health care finance and delivery: what
      about Africa?
AB  - This paper applies concentration curves and indices, that have been previously
      used to analyze progressivity in health care finance and horizontal equity in
      health care delivery in developed countries, to a 1998-1999 household survey
      about health care expenditures and utilization carried out in four francophone
      West African capitals (Abidjan, Bamako, Conakry and Dakar). The paper also uses
      statistical inference for testing stochastic dominance relationship between
      curves, a technique already applied in the literature about equity in taxation,
      as the criterion for making rigorous inequality comparisons. In all four
      capitals, the results strongly suggest a regressive pattern of payments for
      health care, with lower income groups bearing an higher burden of health
      expenditures as a proportion of their income than do the higher income segments
      of the population. As soon as dominance between concentrations curves is
      statistically tested, results appear less conclusive, notably for the groups of
      population affected by severe morbidity, on the issue of horizontal inequity in
      health care delivery, which requires that persons with similar medical need be
      treated equally. Some recommendations are made for the use of equity measurements
      in access to care for future evaluations of the impact of health care reforms in
      Africa.

PMID- 16584804
TI  - Seeking a second opinion: do patients need a second opinion when practice
      guidelines exist?
AB  - INTRODUCTION: Patients often search for a second opinion (i.e., a search for
      additional information on the diagnosis and/or treatment options and the
      potential prognosis, which will help the patient decide what to do or not to do,
      where, with whom and how). The scope of this phenomenon is not well documented.
      Also it is not clear if this is warranted or not. This paper aims to explore
      whether knowing that his clinician follows practice guidelines eliminates the
      need of a patient's to seek a second opinion. Given that practice guidelines
      should allow each patient to benefit from the best current clinical evidence, one
      might wonder if in such a context a second opinion is still necessary, and if so,
      for what reasons? METHODS: We review the literature to find the reasons that may
      prompt a patient to seek a second opinion before the implementation of practice
      guidelines. We then analyse, from a conceptual point of view, whether for
      'informed patient' (i.e., one who knows about and understands practice
      guidelines) these reasons still hold after the implementation of practice
      guidelines and if new reasons for seeking a second opinion have emerged. We also
      discuss practical limitations to searching for a second opinion. RESULTS: We show
      that even if some reasons, like the search for a second opinion to check whether
      the treatment prescribed by the first physician is appropriate or not, can be
      questioned after the implementation of practice guidelines, an 'informed patient'
      may still wish to seek a second opinion stemming from new reasons which have
      emerged after the introduction of practice guidelines, e.g., to determine which
      practice guidelines his physician follows and whether they are appropriate to his
      case. SUMMARY AND CONCLUSION: We conclude that the implementation of practice
      guidelines will not eliminate the need for a second opinion consultation. On the
      contrary, the use of guidelines can even stimulate a broader request for second
      opinions. This conclusion however needs to be validated in an empirical study.

PMID- 16584805
TI  - Role of vinculin in regulating focal adhesion turnover.
AB  - Although vinculin (-/-) mouse embryo fibroblasts assemble focal adhesions (FAs),
      they spread more slowly, less extensively, and close a wound more rapidly than
      vinculin (+/+) cells. To investigate the structure and dynamics of FAs in these
      cells, we used real-time interference reflection microscopy (IRM) thus avoiding
      the need to express exogenous GFP-tagged FA proteins which may be misregulated.
      This showed that the FAs were smaller, less abundant and turned over more rapidly
      in vinculin null compared to wild-type cells. Expression of vinculin rescued the
      spreading defect and resulted in larger and more stable FAs. Phosphatidylinositol
      4,5-bisphosphate (PIP2) is thought to play a role in vinculin activation by
      relieving an intramolecular association between the vinculin head (Vh) and tail
      (Vt) that masks the ligand binding sites in Vh and Vt. To investigate the role of
      the vinculin/PIP2 interaction in FA dynamics, we used a vinculin mutant lacking
      the C-terminal arm (residues 1053-1066) and referred to as the deltaC mutation.
      This mutation reduced PIP2 binding to a Vt deltaC polypeptide by >90% compared to
      wild type without affecting binding to Vh or F-actin. Interestingly, cells
      expressing the vinculin deltaC mutant assembled remarkably stable FAs. The
      results suggest that vinculin inhibits cell migration by stabilising FAs, and
      that binding of inositol phospholipids to Vt plays an important role in FA
      turnover.

PMID- 16584807
TI  - Expression of HMGA2 variants during oogenesis and early embryogenesis of Xenopus
      laevis.
AB  - The high mobility group proteins A2 (HMGA2) have been implicated in the control
      of cell proliferation and differentiation, in particular during embryogenesis.
      Here, we used Xenopus laevis to analyze HMGA2 gene expression patterns during
      oogenesis and early embryogenesis. We found two functional XlHMGA2 isoforms,
      which we named XlHMGA2alpha and XlHMGA2beta. As revealed by RT-PCR, real-time PCR
      and whole-mount in situ hybridization both mRNAs are maternally produced and
      stored in eggs. Whole-mount in situ hybridizations revealed a conspicuous
      redistribution of the XlHMGA2 transcripts during early embryogenesis. Initially,
      during oogenesis and in eggs, the transcripts are uniformly distributed in the
      cytoplasm. With activation of the eggs the transcripts accumulate near the animal
      pole and remain in the juxtanuclear regions of animal pole blastomeres until
      midblastula transition. According to real-time PCR data, XlHMGA2alpha appears to
      be preferentially expressed during oogenesis and after midblastula transition,
      whereas XlHMGA2beta expression predominates after neurulation, suggesting an
      individual transcriptional regulation.

PMID- 16584806
TI  - The slaty mutation affects eumelanin and pheomelanin synthesis in mouse
      melanocytes.
AB  - The slaty (Dct(slt)) mutation is known to reduce the activity of dopachrome
      tautomerase (DCT) in melanocytes. However, it is unknown whether the reduced DCT
      activity leads to a defect in the proliferation and differentiation of mouse
      melanocytes. To address this point, the proliferation and differentiation of
      neonatal melanocytes from Dct(slt)/Dct(slt) congenic mice in serum-free primary
      culture were investigated in detail. The proliferation of slaty epidermal
      melanoblasts/melanocytes in culture did not differ from that of wild-type mice.
      However, the differentiation was greatly inhibited. Tyrosinase (TYR) activity
      detected by dopa reaction as well as staining of DCT in slaty melanocytes was
      greatly reduced. The content of eumelanin in cultured slaty melanocytes was
      reduced, whereas the content of pheomelanin in media derived from cultured 7.5
      day-old slaty melanocytes was greatly increased. The contents of eumelanin and
      pheomelanin in the neonatal slaty epidermis and dermis were reduced, except that
      the pheomelanin content in 3.5-day-old dermis was increased. These results
      suggest that the slaty mutation affects both eumelanin and pheomelanin synthesis
      in developmental stage-specific and skin site-specific manners, and, in addition,
      the gene controls the differentiation of melanocytes via the regulation of
      activity of TYR in addition to its own DCT.

PMID- 16584808
TI  - The release of Hsp70 from A431 carcinoma cells is mediated by secretory-like
      granules.
AB  - In our earlier work we have demonstrated that the treatment of squamous carcinoma
      cell line A431 with a pharmacological inhibitor of phospholipase C activity,
      U73122, resulted in fast release of stress-inducible heat shock protein 70
      (Hsp70) into the extracellular medium (Evdonin et al., Cancer Cell Int., 4, 2,
      2004). The purpose of the present study was to identify cellular organelles
      involved in the release of Hsp70 from A431 cells. We determined that Hsp70 is
      present in granules located at the periphery of cells, which had been treated
      with U73122 or subjected to heat shock. An inhibitor of the classical protein
      export pathway, brefeldin A was found to prevent the U73122-induced appearance of
      Hsp70 in the extracellular medium and in the peripheral granules. These findings
      suggest that vesicular transport is involved in Hsp70 release. The Hsp70
      containing granules did not carry markers specific for lipid bodies, endosomes,
      or lysosomes. However, they were positive for a marker of secretory granules,
      i.e. chromogranin A. The levels of extracellular Hsp70 and chromogranin A were
      found to increase simultaneously. The secretory-like granule-dependent transport
      of Hsp70 was also studied in minimally transformed human HaCaT keratinocytes. We
      found that after U73122 and heat stress treatment, HaCaT cells secreted Hsp70 in
      a manner similar to A431 cells. Collectively our results suggest that human
      keratinocyte-derived cells release Hsp70 in the extracellular medium through a
      pathway involving secretory-like granules.

PMID- 16584809
TI  - TNF-alpha mediated transport of NF-kappaB to the nucleus is independent of the
      cytoskeleton-based transport system in non-neuronal cells.
AB  - In unstimulated cells, proteins of the nuclear factor kappaB (NF-kappaB)
      transcription factor family are sequestered in the cytoplasm through interactions
      with IkappaB inhibitor proteins. Tumor necrosis factor alpha (TNF-alpha)
      activates the degradation of IkappaB-alpha and the nuclear import of cytoplasmic
      NF-kappaB. Nuclear localization of numerous cellular proteins is mediated by the
      ability of the cytoskeleton, usually microtubules, to direct their perinuclear
      accumulation. In a former study we have shown that activated NF-kappaB rapidly
      moves from distal processes in neurons towards the nucleus. The fast transport
      rate suggests the involvement of motor proteins in the transport of NF-kappaB.
      Here we address the question how NF-kappaB arrives at the nuclear membrane before
      import in non-neuronal cells, i.e., by diffusion alone or with the help of active
      transport mechanisms. Using confocal microscopy imaging and analysis of nuclear
      protein extracts, we show that NF-kappaB movement through the cytoplasm to the
      nucleus is independent of the cytoskeleton, in the three cell lines investigated
      here. Additionally we demonstrate that NF-kappaB p65 is not associated with the
      dynein/dynactin molecular motor complex. We propose that cells utilize two
      distinct mechanisms of NF-kappaB transport: (1) signaling via diffusion over
      short distances in non-neuronal cells and (2) transport via motor proteins that
      move along the cytoskeleton in neuronal processes where the distances between
      sites of NF-kappaB activation and nucleus can be vast.

PMID- 16584810
TI  - Identification of a cytochrome P450 cDNA (CYP98A5) from Phaseolus vulgaris,
      inducible by 3,5-dichlorosalicylic acid and 2,6-dichloro isonicotinic acid.
AB  - To investigate the involvement of cytochrome P450s in the metabolism of plants
      treated with xenobiotic agrochemicals, bean leaves were treated with 3,5
      dichlorosalicylic acid (DC-SA), a priming agent of plant defense and 2,6
      dichloroisonicotinic acid (DC-INA), a chemical inducer of systemic acquired
      resistance. Through the use of directed differential display reverse
      transcription polymerase chain reactions, a differentially expressed cDNA
      amplicon, found to be up-regulated by both DC-SA and DC-INA treatment, was
      identified as a cytochrome P450 cDNA, CYP98A5. The nucleotide sequence indicates
      extensive homology to 3'-hydroxylases of p-coumaroyl esters. Dot blot analysis of
      leaves treated with various SA and isonicotinic acid derivatives showed enhanced
      expression of CYP98A5 due to DC-SA and DC-INA. Northern blot analysis of a time
      dependent induction study of CYP98A5 in treated bean leaves indicated that DC-SA
      induces CYP98A5 mRNA transcripts earlier than DC-INA. Both inducers resulted in
      high transcript levels 24-48 h after treatment. The up-regulation of CYP98A5 is
      supportive of the conditioning and sensitizing effects of DC-SA and DC-INA to
      elicit a more rapid and effective defense response.

PMID- 16584811
TI  - Perceptions of food risk management among key stakeholders: results from a cross
      European study.
AB  - In designing and implementing appropriate food risk management strategies, it is
      important to examine how key stakeholders perceive both the practice and
      effectiveness of food risk management. The objective of this study is to identify
      similarities and differences in perceptions of, and attitudes to, food risk
      management practices held by consumers and experts with an interest in food
      safety. Focus groups were conducted in five European countries chosen for their
      (hypothesised) cultural differences in attitudes towards risk: Denmark, Germany,
      Greece, Slovenia and the UK. Content analysis was carried out on the resulting
      texts and (sub) categories were identified within the analysis framework to
      facilitate the capture of emerging themes. Five key themes were identified as
      common to the perceptions of both consumers and experts, although these are not
      represented in the same way by both groups. These key themes are: (1) efforts
      made by the responsible authorities to manage food risks; (2) responsibility for
      prevention and management of food risks; (3) how priorities are established
      within regulatory systems; (4) scientific progress and its implications for food
      risk management; and (5) media attention and food safety incidents. Although some
      similarities emerged between the groups, differences were also identified. For
      example, experts appeared to be highly negative about media influences, whereas
      consumers appeared more indifferent about media influences and motives. These
      different perspectives need to be addressed in order to reduce the perceptual
      distance between key stakeholders, and in particular, to enhance consumer
      confidence in the food risk management system. Based on the study findings,
      recommendations for food risk management policies are outlined.

PMID- 16584812
TI  - Functional interaction between nociceptin/orphanin FQ and alpha-melanocyte
      stimulating hormone in the regulation of feeding.
AB  - Nociceptin/orphanin FQ (N/OFQ), an endogenous agonist of the opioid N/OFQ (NOP)
      receptor, increases food intake when administered centrally. As N/OFQ is part of
      a larger neural network that governs consummatory behavior, presumably its
      orexigenic properties stem from interplay with other neuropeptidergic components
      of the feeding-related circuitry. One such peptide may be the ligand of the
      melanocortin-3 and -4 receptors, alpha-melanocyte-stimulating hormone (alpha
      MSH), which is known to inhibit food intake. The aim of the present study was to
      establish whether there is a functional "interaction" between N/OFQ and alpha-MSH
      in the regulation of feeding. By using double immunostaining for c-Fos and alpha
      MSH, we found that intracerebroventricular (i.c.v.) injection of N/OFQ at a
      10nmol dose that moderately prolongs deprivation-induced food intake in rats,
      decreases activation of alpha-MSH neurons involved in feeding termination.
      However, i.c.v. injections of alpha-MSH at doses previously established to reduce
      deprivation-induced feeding, do not decrease hyperphagia generated by N/OFQ in ad
      libitum-fed animals. Our results suggest that while alpha-MSH does not appear to
      modify the orexigenic response to N/OFQ in sated rats, the NOP receptor ligand
      promotes a decrease in activation of neurons synthesizing the anorexigenic
      peptide, alpha-MSH, at the time of re-feeding. Thus, to some degree, the
      stimulatory effect of N/OFQ on consumption may arise from this peptide's
      inhibitory influence on activity of anorexigenic pathways containing alpha-MSH.

PMID- 16584813
TI  - Synthesis and cancer antiproliferative activity of new histone deacetylase
      inhibitors: hydrophilic hydroxamates and 2-aminobenzamide-containing derivatives.
AB  - New series histone deacetylase inhibitors comprising a hydroxamic acid or 2
      aminobenzamide group as a zinc-chelating function were synthesized and evaluated
      for antiproliferative activities against a panel of human cancer cells. The 2
      aminobenzamide series inhibitors generally had the potency in cell growth
      inhibitions comparable to that of MS-275. Among them, the compound having a (3,4
      difluorobenzyl)(2-hydroxyethyl)amino group at one end and a 2-aminobenzamide
      group at the other of molecule showed the most promising profile as an anticancer
      drug candidate, since it had a comparatively low toxicity as did MS-275 against a
      normal fibroblast cell CCD-1059SK. Additionally, the derivative exhibited a high
      recovery in human plasma stability test.

PMID- 16584814
TI  - A short report on clinical evaluation of RIX4414: highlights of world-wide
      development.

PMID- 16584815
TI  - Attenuated aroA Salmonella enterica serovar Typhimurium does not induce
      inflammatory response and early protection of gnotobiotic pigs against parental
      virulent LT2 strain.
AB  - Cytokine and inflammatory response against virulent LT2 strain and its attenuated
      aroA deletion mutant of Salmonella enterica serovar Typhimurium were compared in
      gnotobiotic pigs. Contrary to the parental strain, the auxotrofic mutant did not
      induce IL-1beta, IL-18, TNF-alpha, and IFN-gamma in the ileum and plasma 24h
      after the infection, did not cause pathological changes in ileal epithelium and
      mesenteric lymph nodes or immunoreactivity of gp91 phox and peroxynitrite and was
      not immunostained for GroEL stress protein. The absence of induction of
      proinflammatory cytokines may be a reason why aroA mutant was unable to elicit
      any inflammatory response and protect pigs against challenge with virulent LT2
      strain administered 24h later.

PMID- 16584816
TI  - Natural radioactivity and radon exhalation in building materials used in Italian
      dwellings.
AB  - Forty-two samples of building materials commonly used in Italian dwellings were
      surveyed for natural radioactivity. External (gamma), as defined and used by the
      European Commission, and internal (alpha) hazard indexes were calculated and
      radon specific exhalation rate and emanation fraction were measured. The
      accumulation method, by using the E-PERM electret ion chambers, was employed to
      determine specific exhalation rates of 222Rn. Several of the materials had hazard
      indexes that exceeded the European Commission limit values. However, it was
      evident that limit values for internal hazard indexes set based on Rn emanation
      should take into account the properties and use of the materials. For example, Rn
      emanation from basalt and glazed tiles was substantially lower than the Rn
      emanation from other materials with similar hazard indexes. Clearly there is need
      for improved guidelines and regulations in this area.

PMID- 16584817
TI  - Treatment of iatrogenic submandibular sialocele with botulinum toxin. Case
      report.
AB  - We report the case of a 40-year-old woman with a submandibular sialocele
      (diagnosed by ultrasonography and magnetic resonance sialography) after
      sialoadenectomy for sialolithiasis. Type A botulinum toxin was injected
      percutaneously under colour Doppler ultrasonographic guidance into the sialocele
      and the residual salivary gland. Five months later the submandibular swelling had
      gone, and we gave a second injection of botulinum toxin to block any residual
      secretory activity. There were no side effects. This is, as far as we know, the
      first published report of the use of botulinum toxin to treat an iatrogenic
      submandibular sialocele.

PMID- 16584818
TI  - Nodular fasciitis: restitutio ad integrum.

PMID- 16584819
TI  - Behavioral changes in fish exposed to phytoestrogens.
AB  - We investigated the behavioral effects of exposure to waterborne phytoestrogens
      in male fighting fish, Betta splendens. Adult fish were exposed to a range of
      concentrations of genistein, equol, beta-sitosterol, and the positive control
      17beta-estradiol. The following behaviors were measured: spontaneous swimming
      activity, latency to respond to a perceived intruder (mirror reflection),
      intensity of aggressive response toward a perceived intruder, probability of
      constructing a nest in the presence of a female, and the size of the nest
      constructed. We found few changes in spontaneous swimming activity, the latency
      to respond to the mirror, and nest size, and modest changes in the probability of
      constructing a nest. There were significant decreases, however, in the intensity
      of aggressive behavior toward the mirror following exposure to several
      concentrations, including environmentally relevant ones, of 17beta-estradiol,
      genistein, and equol. This suggests that phytoestrogen contamination has the
      potential to significantly affect the behavior of free-living fishes.

PMID- 16584820
TI  - Use of bone meal amendments to immobilise Pb, Zn and Cd in soil: A leaching
      column study.
AB  - The aim of this study is to test the stabilisation of metals in contaminated
      soils via the formation of low-solubility metal phosphates. Bone apatite, in the
      form of commercially available bone meal, was tested as a phosphate source on a
      mine waste contaminated made-ground with high levels of Pb, Zn and Cd. Triplicate
      leaching columns were set up at bone meal to soil ratios of 1:25 and 1:10, in
      addition to unamended controls, and were run for 18 months. The columns were
      irrigated daily with a synthetic rain solution at pH of 2, 3, and 4.4. After 100
      days, the leachate Pb, Zn and Cd concentrations of all amended columns were
      significantly reduced. For 1:10 treatments, release of these metals was
      suppressed throughout the trial. For 1:25 treatments, Zn and Cd concentrations in
      the leachates began to increase after 300 days. DTPA and water extractions showed
      that Pb and Cd were more strongly held in the amended soils. This study concludes
      that the complexity of soil processes and the small quantities of metals
      sequestered precluded determination of a metal immobilisation mechanism.

PMID- 16584821
TI  - Diagnostic indicators of elevated nitrogen deposition.
AB  - Tissue N content of mosses, which has been shown to be an indicator of enhanced
      N, was studied at a range of locations dominated either by wet or dry deposited
      and oxidised and reduced forms of N. Tissue N responded differently to wet and
      dry deposited N. For a 1 kg ha(-1) y(-1) increase in N deposition, tissue N
      increased by 0.01% at wet deposition sites but by 0.03% at sites dominated by dry
      deposited NH3. Tissue N at wet deposition sites responded more to concentrations
      of NO3- and NH4+ in precipitation (r(2) 0.63) than to total N deposition (r(2)
      0.27), concentration explaining 66% of the variation in tissue N, wet deposition
      33%. The study clearly concludes that tissue N concentration in mosses provides a
      good indication of N deposition at sites where deposition is dominated by NH3,
      and is also valuable in identifying vegetation exposed to large concentrations of
      NH4+ or NO3-, in wet deposition dominated areas, such as hilltops and wind
      exposed woodland edges.

PMID- 16584822
TI  - Does lipophilicity of toxic compounds determine effects on drought tolerance of
      the soil collembolan Folsomia candida?
AB  - The ability of Collembola to survive drought stress is crucial for their
      distribution in the terrestrial environment. Previous studies have suggested that
      several toxic compounds affect the drought tolerance of Folsomia candida in a
      synergistic manner and that these compounds have the feature in common that they
      elicit their toxicity by causing membrane damage. We hypothesised that the
      detrimental effect of toxic chemicals on drought tolerance in F. candida depends
      on the lipophilicity (log K(ow)) of the compound because a higher log K(ow) would
      mean a closer interaction with membranes. In this study the three chemicals 4
      nonylphenol, pyrene and p,p'-DDE were tested. Surprisingly, 4-nonylphenol, with
      the lowest log K(ow), was the most potent with respect to reducing drought
      tolerance followed by pyrene, suggesting that interactions between drought
      tolerance and chemical stress do not depend on lipophilicity alone.

PMID- 16584823
TI  - Influences of wetland plants on weathered acidic mine tailings.
AB  - Establishment of Carex rostrata, Eriophorum angustifolium and Phragmites
      australis on weathered, acidic mine tailings (pH approximately 3) and their
      effect on pH in tailings were investigated in a field experiment. The amendments,
      sewage sludge and an ashes-sewage sludge mixture, were used as plant nutrition
      and their influence on the metal and As concentrations of plant shoots was
      analysed. An additional experiment was performed in greenhouse with E.
      angustifolium and sewage sludge as amendments in both weathered and unweathered
      tailings. After one year, plants grew better in amendments containing ashes in
      the field, also in those plants the metal and As shoot concentrations were
      generally lower than in other treatments. After two years, the only surviving
      plants were found in sewage sludge mixed with ashes. No effect on pH by plants
      was found in weathered acidic mine tailings in either field- or greenhouse
      experiment.

PMID- 16584824
TI  - Cultural context and impact of alcohol use in the Sundarban Delta, West Bengal,
      India.
AB  - Hazardous alcohol consumption is a worldwide problem with many locally
      distinctive features across cultures, but studies to guide policy in developing
      countries are notably lacking. This community study aimed to clarify local
      patterns of alcohol use in six villages of West Bengal, India. It considered the
      variety of local alcoholic preparations, who consumed them, when, and where. It
      sought to determine how social changes in the region influence changing patterns
      of acceptable and problem use of alcohol. Ethnographic methods included
      participant observation and focus group discussions. The qualitative data
      analysis of field notes and transcripts included a review of full texts and a
      computer-assisted analysis of thematically coded segments with reference to a
      structured agenda. We found that drinking is an integral feature of the cultural
      landscape. Locally brewed rice beer (handia), palm wine (tadi), distilled country
      liquor (chullu), and so-called Indian-made foreign liquor (IMFL) are consumed in
      these villages. Each is identified with particular segments of society and
      settings in these communities. Reported effects of problem drinking included
      social disturbances, family discord, and domestic violence. Increasing problem
      alcohol use was attributed by villagers to social changes resulting from
      development, which were otherwise valued, such as improved transportation and
      communications. In a field dominated by Western and urban studies, this research
      clarifies features of alcohol availability, use, and acceptance in a neglected
      rural area of India. It illustrates the limitations of western clinical models of
      dependence and the importance of clarifying sociocultural conditions that define
      locally acceptable and problem use.

PMID- 16584825
TI  - Psychological distress among adolescents, and its relationship to individual,
      family and area characteristics in East London.
AB  - This paper identifies factors associated with variation in psychosocial distress
      among adolescents in a relatively deprived and ethnically diverse inner city
      setting in London, UK. The research draws on literature which discusses whether
      neighbourhood socio-economic conditions are associated with mental health, as
      well as attributes of individual adolescents and their families. We report an
      analysis of data from the Research with East London Adolescents: Community Health
      Survey (RELACHS). The survey collected data on mental health measured by the
      Strengths and Difficulties Questionnaire (SDQ), and on various aspects of
      individual and family circumstances. These data were linked with information
      about social and economic conditions in 'middle layer standard output areas'
      (MSOA) used for the population Census 2001, having a mean total population of
      6767 in the study area. Census statistics including the Indices of Deprivation
      for 2004 proposed by the Office of the Deputy Prime Minister, were used to
      describe the socio-economic conditions within these areas. Although the socio
      economic disparities among small areas were not typical of those across the whole
      of the country, there were differences in levels of deprivation and crime, social
      fragmentation, and ethnic composition. A Bayesian regression analysis using Gibbs
      sampling in the programme WinBugs investigated whether there was variability in
      SDQ at both individual and area (MSOA) level, and whether the predictor variables
      at both levels were significantly associated with SDQ. Individuals from Asian or
      Black ethnic groups, and those in families with harmonious relationships and no
      financial stress had significantly lower SDQ scores, i.e. better health. Those
      who had special educational needs or long standing illness, or were from
      reconstituted families had significantly worse SDQ scores. About 6% of the
      variation in SDQ was associated with area differences. However, this area
      variation was not related to differences in area indicators of socio-economic
      deprivation, crime or social fragmentation. There was a complex association
      between SDQ and ethnic composition of neighbourhoods.

PMID- 16584826
TI  - Quantification of extrapulmonary translocation of intratracheal-instilled
      particles in vivo in rats: effect of lipopolysaccharide.
AB  - Particulate air pollution is associated with respiratory and cardiovascular
      morbidity and mortality. However, important uncertainties remain in the
      quantification of extrapulmonary translocation of ultrafine particles into blood
      circulation. Therefore, the widely used radioiodinated technique was applied to
      radiolabel polystyrene particles with an average diameter of 56.4 and 202 nm,
      respectively. The extrapulmonary distribution of these particles (3.7 x 10(5)
      Bq/rat) was quantified at 0.5, 2, 24 and 120 h after intratracheal instillation
      in rats. Moreover, we have taken into account the possible involvement of
      pulmonary inflammation in this process. Rats which received a single
      intratracheal instillation of free 125I or a single intravenous injection of
      labeled ultrafine particles served as control. The results indicated that the
      pulmonary deposition of radioactivity was almost unchanged for both sizes. Only
      small amounts of radioactivity (1.64-2.49%) were recovered in blood shortly after
      administration of both types of particle, in healthy rats. However, the extent of
      particle translocation into the blood of the ultrafine size following the
      pretreatment with lipopolysaccharides was significantly higher (from 1.96 +/-
      0.67 to 4.73 +/- 0.31%) compared to larger particles (from 2.19 +/- 0.77 to 2.21
      +/- 0.64%). In conclusion, our findings suggest that only a small fraction of
      intratracheal-instilled ultrafine particles can pass rapidly into systemic
      circulation, but this translocation is markedly increased following LPS
      pretreatment. Thus, pulmonary inflammation seems to play a major role in
      enhancing the extrapulmonary translocation of particles.

PMID- 16584827
TI  - Regulation of the cadmium stress response through SCF-like ubiquitin ligases:
      comparison between Saccharomyces cerevisiae, Schizosaccharomyces pombe and
      mammalian cells.
AB  - Saccharomyces cerevisiae has developed several mechanisms to cope with exposure
      to cadmium. In particular, the sulfur compound glutathione plays a pivotal role
      in cadmium detoxification, and exposure to cadmium leads to a wide reorganization
      of S. cerevisiae transcriptome and proteome, resulting in a significant increase
      in glutathione synthesis. Met4, the transcriptional activator of the sulfur
      metabolism enzymes, is a critical actor in this reorganization. Recent work has
      uncovered a part of the mechanism of cadmium-induced Met4 regulation, and showed
      that it occurs trough the SCF ubiquitin ligase complex SCF(Met30). We discuss
      this regulation in S. cerevisiae and compare it with the regulation of two other
      transcriptional activators involved in cadmium detoxification: the
      Schizosaccharomyces pombe Zip1, regulated by SCF(Pof1), and the mammalian Nrf2,
      regulated by the SCF-like ubiquitin ligase Cul3:Rbx1:Keap1.

PMID- 16584828
TI  - Mortality after trauma intubation without drugs in Scottish emergency
      departments.
AB  - BACKGROUND: Trauma patients who are intubated without anaesthetic drugs in the
      pre-hospital phase of care have universally poor outcomes. This study aimed to
      determine the mortality of trauma patients intubated without drugs in emergency
      departments in Scotland. METHODS: This retrospective cohort study used the
      prospective Scottish Trauma Audit Group (STAG) database to identify how many
      patients were intubated and how many required drugs for intubation between 1
      January 1999 and 31 December 2002. The mortality of those intubated with drugs
      and without drugs was determined from the database. RESULTS: 24,756 patients were
      included in the STAG database. There were 1469 intubations: 1287 with drugs and
      182 without drugs. 92.5% of all intubations were for blunt trauma. There was no
      difference in the proportion of males or median age between groups. Median GCS
      was 8 (E1M5V2) in the drugs group and 3 (E1M1V1) in the no drugs group (p<0.001).
      Median ISS was higher in those intubated without drugs (33 versus 25, p<0.001).
      Median RTS and probability of survival were lower in those intubated without
      drugs (both p<0.001). Mortality was higher in those intubated without drugs
      (91.2% versus 29.4%, p<0.001). Sixteen patients, intubated without drugs,
      survived. These patients had a higher median respiratory rate (9 versus 0,
      p=0.013) and higher median systolic blood pressure (80 mmHg versus 0 mmHg,
      p=0.041) than non-survivors. CONCLUSION: Trauma patients in Scottish emergency
      departments who are intubated without drugs have high mortality rates. Outcomes
      are not universally fatal and aggressive resuscitation efforts may be of benefit
      to a small number of such patients.

PMID- 16584829
TI  - Concentrations of plasminogen activators and their inhibitors in blood
      preconceptionally, during and after pregnancy.
AB  - BACKGROUND: Haemostasis is a complex balance of activating and inhibitory
      pathways resulting in coagulation and lysis. Normal pregnancy is associated with
      hypercoagulation that is even more profound in complicated pregnancies.
      OBJECTIVE: To study the role of the plasminogen-activator system in complicated
      pregnancy with regard to haemostasis, it is essential to have reference values of
      components of this system during uneventful pregnancy. In this study we
      investigated the concentrations of six different components of the plasminogen
      activator system preconceptionally, during and after uncomplicated pregnancies.
      MATERIAL AND METHODS: Tissue-type and urokinase-type plasminogen activator (tPA
      and uPA), plasminogen inhibitor type-1 and -2 (PAI-1 and-2), and the complexes
      between tPA and PAI-1, and between uPA and PAI-1 (tPA-PAI-1, uPA-PAI-1) were
      measured by ELISAs in blood obtained preconceptionally, at 6, 10, 20, 32 weeks of
      gestation, and 6 weeks after delivery in uncomplicated pregnancies (n=41; all six
      parameters n=22). RESULTS: tPA and uPA concentrations decreased in the first 10
      weeks of pregnancy and subsequently increased in the third trimester. PAI-1
      concentrations increased in the third trimester and PAI-2 concentrations
      increased throughout pregnancy (preconception versus 32 weeks of gestation; 38.73
      versus 102.23ng/ml, and 0.024 versus 151.06ng/ml, respectively). tPA-PAI-1 and
      uPA-PAI-1 complex concentrations decreased in the first trimester, followed by an
      increase in the third trimester. The concentrations of all components returned to
      the preconception values 6 weeks after delivery. CONCLUSION: This study provides
      longitudinal data on activating and inhibitory components of the plasminogen
      activator system during pregnancy. Insight in the longitudinal changes in these
      concentrations may be of help in the understanding of the thrombotic tendency in
      pregnancy complications such as preeclampsia.

PMID- 16584830
TI  - Interleukin-18 gene promoter polymorphisms and recurrent spontaneous abortion.
AB  - BACKGROUND: IL-18 is a multifunctional cytokine capable of inducing either Th1 or
      Th2 polarization depending on the immunologic milieu. IL-18 is detected at the
      materno-fetal interface very soon in early pregnancy. Two polymorphisms in the
      promoter region of the IL-18 gene at positions of -607 and -137 appear to have
      functional impacts. OBJECTIVE: This study attempts to evaluate the frequency of
      these two polymorphisms in the IL-18 gene promoter in patients with recurrent
      spontaneous abortion (RSA) and normal pregnant women. SUBJECTS AND METHODS: One
      hundred and two RSA patients and 103 healthy pregnant women were enrolled in this
      study. Single nucleotide polymorphisms of the IL-18 gene at positions -607 (C/A)
      and -137 (G/C) were analyzed by the sequence-specific PCR method. RESULTS: There
      was no significant association between the allele, genotype, and haplotype
      frequencies of the two single nucleotide polymorphisms (SNPs) in the IL-18 gene
      promoter and RSA. CONCLUSION: The results of this study showed that IL-18 gene
      promoter polymorphisms at positions -607 and -137 did not confer susceptibility
      to RSA in southern Iranian patients.

PMID- 16584831
TI  - Patients with three or less dominant follicles may not be associated with reduced
      pregnancy rate of in vitro fertilization treatment.
AB  - OBJECTIVES: The management of poor ovarian responders remains a great challenge
      in in vitro fertilization (IVF) treatment. This study compared implantation and
      pregnancy rates among women who developed <or=3 dominant follicles of >or=16 mm
      in diameter and those who had >3 dominant follicles after ovarian stimulation.
      STUDY DESIGN: Retrospective study. RESULTS: Out of 911 consecutive patients
      receiving ovarian stimulation between January 2000 and December 2002, 894 (98.1%)
      patients underwent oocyte retrieval. Women with <or=3 dominant follicles were
      significantly older, required a longer duration and a higher dosage of
      gonadotrophin but produced lesser number of developing follicles, number of
      oocytes aspirated and number of embryos frozen when compared with those with >3
      dominant follicles. Despite a significantly higher percentage of non-elective
      single embryo transfer in women with <or=3 dominant follicles, implantation rate,
      pregnancy rate and pregnancy outcomes were comparable for women with <or=3 and >3
      dominant follicles. CONCLUSION: Implantation and pregnancy rates appeared to be
      comparable for women who developed <or=3 and >3 dominant follicles during IVF
      treatment.

PMID- 16584832
TI  - Kinetic analysis of the anaerobic digestion of untreated vinasses and vinasses
      previously treated with Penicillium decumbens.
AB  - A kinetic study was carried out on the anaerobic digestion of untreated vinasses
      and vinasses previously fermented with Penicillium decumbens. Two 1-l volume
      continuous-flow stirred tank reactors (CFSTR) operating at mesophilic temperature
      (35 degrees C) were used for the study. One reactor was fed with untreated
      vinasses (COD concentration of 80.5 g/l) and the other with vinasses previously
      fermented (COD concentration of 23.0 g/l). Both reactors were operated at organic
      loading rates in the range of 1.5-7.5 g chemical oxygen demand (COD)/l-d. The
      results obtained were evaluated using the Chen-Hashimoto methane production model
      to determine the values of the maximum specific growth rate (micromax) and the
      model kinetic constant (K) of the process for each case studied. The kinetic
      constants (micromax and K) were affected by the pre-treatment, and the respective
      values were 9.6 and 6.9 times higher for pretreated vinasses than those of
      untreated vinasses. This was significant at the 95% confidence level. This
      behaviour is believed to be due to the lower levels of phenolic compounds present
      in the pretreated vinasses, as compared to untreated vinasses, resulting in an
      improved process performance, kinetics and stability. Finally, the experimental
      values of methane production were reproduced with deviations equal to or less
      than 4% and 10% for pretreated and untreated vinasses, respectively.

PMID- 16584833
TI  - Statistical approach for evaluating the significance of generating new data to
      the management of the brackish groundwater fields in Kuwait.
AB  - The brackish groundwater production fields in Kuwait have been drilled
      intensively during the past three decades. However, poor spatial distribution of
      some of the measured parameters and limited measurements of others are forcing
      extended extrapolation during numerical simulations of management schemes. On the
      other hand, operational, time and budget constraints allow only limited
      additional field-generated data, raising the question of the significance of
      their impact on numerical modeling results. This study evaluates this
      significance by using nearest neighbor statistics and a synthesized data set to
      assess the impacts of a proposed field investigation on the spatial distribution
      and kriged values of transmissivity and storage coefficient arrays of the
      brackish groundwater production fields. A scale for the significance of the
      impacts was prepared based on the sensitivity of the aquifer system towards the
      studied properties. The transmissivity data array indicated a 25% reduction in
      the maximum distance and an 8% increase in the interquartile of the nearest
      neighbor analysis. The storage coefficient data arrays indicated the extension of
      the covered area to reach the southern boundary of the study area, which was
      reflected in more than doubling the maximum distance between the nearest
      neighbors. For the kriged values of the transmissivity, about 35% of the study
      area was significantly changed due to the addition of the new data points, while
      only 10% of the study area was significantly changed for the storage coefficient
      values. Overall, while the spatial distribution indicators were not conclusive,
      the significance of the new data was clear in the changes in the kriged values of
      the aquifer properties. Additionally, this approach highlights the aquifer test
      locations where the generated data had no impact on the kriged values, which may
      be utilized for optimizing the allocation and number of the aquifer tests.

PMID- 16584834
TI  - Aerobic treatment of palm oil mill effluent.
AB  - In this study treatment of palm oil mill effluent (POME) was investigated using
      aerobic oxidation based on an activated sludge process. The effects of sludge
      volume index, scum index and mixed liquor suspended solids during the
      acclimatizing phase and biomass build-up phase were investigated in order to
      ascertain the reactor stability. The efficiency of the activated sludge process
      was evaluated by treating anaerobically digested and diluted raw POME obtained
      from Golden Hope Plantations, Malaysia. The treatment of POME was carried out at
      a fixed biomass concentration of 3900+/-200mg/L, whereas the corresponding sludge
      volume index was found to be around 105+/-5mL/g. The initial studies on the
      efficiency of the activated sludge reactor were carried out using diluted raw
      POME for varying the hydraulic retention time, viz: 18, 24, 30 and 36h and
      influent COD concentration, viz: 1000, 2000, 3000, 4000 and 5000mg/L,
      respectively. The results showed that at the end of 36h of hydraulic retention
      time for the above said influent COD, the COD removal efficiencies were found to
      be 83%, 72%, 64%, 54% and 42% whereas at 24h hydraulic retention time they were
      57%, 45%, 38%, 30% and 27%, respectively. The effectiveness of aerobic oxidation
      was also compared between anaerobically digested and diluted raw POME having
      corresponding CODs of 3908 and 3925mg/L, for varying hydraulic retention time,
      viz: 18, 24, 30, 36, 42, 48, 54 and 60h. The dissolved oxygen concentration and
      pH in the activated sludge reactor were found to be 1.8-2.2mg/L and 7-8.5,
      respectively. The scum index was found to rise from 0.5% to 1.9% during the
      acclimatizing phase and biomass build-up phase.

PMID- 16584835
TI  - E-NTPDase 3 (ATP diphosphohydrolase) from cardiomyocytes, activity and expression
      are modulated by thyroid hormone.
AB  - Degradation of adenine nucleotides by myocardial cells occurs, in part, by a
      cascade of surface-located enzymes converting ATP into adenosine that has
      important implications for the regulation of the nucleotide/nucleoside ratio
      modulating the cardiac functions. Thyroid hormones have profound effects on
      cardiovascular system, as observed in hypo- and hyperthyroidism. Combined
      biochemical parameters and gene expression analysis approaches were used to
      investigate the influence of tri-iodothyronine (T3) on ATP and ADP hydrolysis by
      isolated myocytes. Cultures of cardiomyocytes were submitted to increasing doses
      of T3 for 24h. Enzymatic activity and expression were evaluated. T3 (0.1 nM)
      caused an increase in ATP and ADP hydrolysis. Experiments with specific
      inhibitors suggest the involvement of an NTPDase, which was confirmed by an
      increase in NTPDase 3 messenger RNA (mRNA) levels. Since T3 promotes an increase
      in the contractile protein, leading to cardiac hypertrophy, it is tempting to
      postulate that the increase in ATP hydrolysis and the decrease in the
      extracellular levels signify an important factor for prevention of excessive
      contractility.

PMID- 16584836
TI  - Activation of the rat scavenger receptor class B type I gene by PPARalpha.
AB  - Peroxisomal proliferator activated receptor alpha (PPARalpha) is activated by
      fibrate drugs which are known to protect against atherosclerosis. The present
      study examines the effects of PPARalpha on SR-BI expression. For this study, a
      rat SR-BI promoter-luciferase reporter gene construct was co-transfected into
      different cell lines with expression vectors that encode for PPARalpha+/-retinoic
      X receptor alpha (RXRalpha). PPARalpha/RXR increased the activity of the SR-BI
      promoter, an effect that was enhanced by clofibrate. Sequence analysis of the rat
      SR-BI promoter revealed the presence of a putative peroxisomal proliferator
      response element (PPRE) at bp -1,622. Electrophoretic mobility shift assays
      demonstrated that PPARalpha and RXRalpha are able to bind to the SR-BI PPRE
      motif. In addition, mutational analysis studies confirmed that this PPRE motif is
      responsible for the PPARalpha/RXRalpha-dependent activation of the rat SR-BI
      promoter in the cell lines examined.

PMID- 16584838
TI  - Doxycycline-regulated co-expression of GDNF and TH in PC12 cells.
AB  - Current gene therapy models for Parkinson's disease (PD) have adapted two
      treatment strategies. One is to restore dopamine (DA) production by delivering
      the genes of DA-synthesizing enzymes such as tyrosine hydroxylase (TH) to the
      striatum to relieve motor symptoms of PD. Another is to block or slow down
      progressive degenerative changes by delivering neurotrophic factors such as glial
      cell line-derived neurotrophic factor (GDNF) to protect the remained neurons. To
      test the assumption that the combination of the two strategies may have a
      compound or synergistic effect, we had constructed tetracycline-inducible (tet
      off) AAV vector carrying GDNF and TH. After co-transfection of PC12 cells with
      this vector and the inducer plasmid, the expression of GDNF and TH protected
      these cells from 1-methyl-4-phenyl-pyridinium-induced injury, and significantly
      increased the content of dopamine in GDNF/TH-expressing cells compared with the
      control. Furthermore, mRNA expression of GDNF and TH could be effectively and
      reversibly regulated by doxycycline (Dox) and the function of GDNF and TH could
      be repressed by Dox. These results suggest that the tet-off AAV vector carrying
      GDNF and TH may be a useful tool for gene therapy in the treatment of PD.

PMID- 16584837
TI  - Specific inhibition of AKT2 by RNA interference results in reduction of ovarian
      cancer cell proliferation: increased expression of AKT in advanced ovarian
      cancer.
AB  - The protein kinase AKT is involved in several signaling pathways that are
      important for tumor development and progression, suggesting that AKT might be an
      interesting target for a molecular tumor therapy. In this study, we investigated
      the AKT expression in ovarian carcinomas and the role of the AKT isoforms to
      ovarian cancer cell proliferation. We observed an increased AKT expression in 58%
      of the primary ovarian carcinomas as compared to normal ovaries by
      immunohistochemistry. AKT expression was significantly associated with positive
      lymph node status (P=0.002) and advanced FIGO stage (P=0.009). In western blot
      analysis, total AKT was expressed in all ovarian cancer cell lines and HOSE
      cells, while phosphorylated AKT was only observed in OVCAR-3 and SKOV-3 cells.
      The isoforms AKT1 and AKT2 were expressed at the mRNA level in all cell lines,
      while no relevant AKT3 mRNA levels were detected by conventional and quantitative
      RT-PCR. To determine the effects on cell proliferation, we used the unselective
      PI3K-inhibitor LY294002 as well as RNA interference to selectively inhibit the
      AKT isoforms. Treatment with LY294002 and the AKT2 siRNA reduced proliferation of
      OVCAR-3 cells. Our results show that AKT is expressed in a subpopulation of
      advanced ovarian carcinomas suggesting a role for this protein in the progression
      of this entity. Deactivation of AKT, especially AKT2 can result in reduction of
      cell growth. Accordingly, AKT is an interesting target for therapeutic
      intervention in ovarian cancer.

PMID- 16584839
TI  - An association study of catechol-O-methyltransferase and monoamine oxidase A
      polymorphisms and personality traits in Koreans.
AB  - Catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA) are both
      involved in the degradation of various biogenic amines which have been
      hypothesized to have a relationship with personality traits. The present study
      investigated the possible relationships between the genotypes of COMT Val158Met
      and MAOA-uVNTR polymorphisms and personality traits measured by the Temperament
      and Character Inventory (TCI). We recruited 286 normal, unrelated Korean subjects
      (138 males and 148 females). There were no associations between the COMT
      Val158Met genotypes or the TCI subscales in the male subjects. However, a
      significant correlation was observed between the COMT genotype and harm avoidance
      (HA, F=6.0, p=0.003) in females. Post hoc analyses showed that the subjects with
      the Met/Met genotype had the lowest mean HA (HA=13.8+/-5.7, p=0.02), Val/Met
      group had an intermediate mean HA score (HA=16.3+/-7.0, p=0.02), and Val/Val
      group had the highest mean HA value (HA=19.6+/-7.0, p=0.02). There were no
      associations between the MAOA-uVNTR and the TCI subscales in either the male or
      female subjects. These results suggest that genetic variants of the COMT
      Val158Met gene may play a role in HA in Korean females but not in males.

PMID- 16584840
TI  - Proteasomal inhibition hypersensitizes differentiated neuroblastoma cells to
      oxidative damage.
AB  - Parkinson's disease (PD) is a multifactorial disease caused by both genetic and
      environmental factors. Alpha-synuclein is of particular interest in PD since it
      is a major component of Lewy bodies and mutations in the alpha-synuclein gene
      were identified in familial PD. Oxidative stress and proteasomal dysfunction are
      implicated in the pathogenesis of PD but their interactions as well as their
      effect on aggregates formation are not yet clear. We therefore examined the roles
      of oxidative stress and proteasomal inhibition on protein aggregates induction in
      naive and neuronally differentiated neuroblastoma SH-SY5Y cells. Neuroblastoma
      cells were stably transfected with wild type (WT) and A53T mutant alpha
      synuclein. Naive and transfected cells were exposed to oxidative stress induced
      by rotenone, SIN-I, FeCl(2,) and to proteasomal inhibition by lactacystin.
      Proteasomal inhibition caused a dose-dependent decrease in viability and induced
      protein aggregates formation containing alpha-synuclein and ubiquitin.
      Proteasomal inhibition induced significantly increased alpha-synuclein
      aggregation in cells expressing mutant alpha-synuclein. Exposure to reactive
      oxygen species (ROS) combined with proteasomal inhibition increased aggregates
      formation. Inclusion body formation and cell death of differentiated
      neuroblastoma cells overexpressing alpha-synuclein can serve as a valuable model
      for elucidating the molecular components that cause neurodegeneration in PD as
      well as evaluating pharmacological interventions.

PMID- 16584841
TI  - Capsaicin-induced vasoconstriction in the mouse knee joint: a study using TRPV1
      knockout mice.
AB  - Capsaicin is the pungent component of chilli peppers that concomitantly activates
      and desensitizes C-fibre and Adelta sensory nerve fibres. Stimulation causes an
      acute neurogenic response including vasodilation, plasma extravasation and
      hypersensitivity. However, in the present study we have shown that capsaicin
      produces a dose-dependent vasoconstrictor effect in the mouse knee joint via
      Transient Receptor Potential Vanilloid 1 (TRPV1) receptor activation. A (125)I
      albumin accumulation technique showed that the intravascular volume of capsaicin
      treated joints in wild type (WT) mice was significantly reduced compared to TRPV1
      knockout mice (p<0.01). Similarly, a laser Doppler technique showed significantly
      reduced blood flow in the capsaicin-treated joints of WT compared to TRPV1
      knockout mice (p<0.001). Pretreatment with guanethinidine (50 mg kg(-1), i.p.)
      had no effect on the vasoconstriction. These data are important considering the
      involvement of TRPV1 receptors in joint disease. The mechanisms underlying the
      vasoconstriction therefore require further investigation.

PMID- 16584842
TI  - Variants in the RAB3A gene are not associated with mental retardation in the
      Chinese population.
AB  - Mental retardation is a common form of cognitive impairment among children. The
      underlying causes of mental retardation are extremely heterogeneous, and include
      significant genetic factors. The coexistence of neuropathology and cognitive
      deficits supports the view that mental retardation is a disorder of brain
      development and plasticity. Rab3A, a member of the Rab small G protein family, is
      a key molecule in modulating basal neurotransmission and contributes to synaptic
      plasticity. The RAB3A gene is located on chromosome 19p13.11, near a region shown
      by a linkage study to be involved in the etiology of mental retardation. Because
      of both its function and chromosomal location, RAB3A is a potential candidate
      susceptibility gene for mental retardation. To investigate the possible genetic
      contribution of the RAB3A gene, we performed a case-control association study
      focused on the Han population of northwestern China using four common SNPs in the
      gene (rs7259012, rs17683539, rs2271882, and rs874628). Pairwise linkage
      disequilibrium analysis showed that the four SNPs were in linkage disequilibrium.
      However, there were no significant differences of either allele or genotype
      frequencies at any of the SNPs nor any significant differences in haplotype
      distributions between cases and controls. In conclusion, we have found no
      evidence for RAB3A conferring susceptibility on mental retardation in the Han
      Chinese population.

PMID- 16584843
TI  - First molecular diagnosis of Babesiavogeli in domestic dogs from Turkey.
AB  - Microscopic examination of Giemsa-stained peripheral blood smears collected from
      three naturally infected dogs originating from Turkey revealed the presence of
      large (around 4.5-5.0 microm) intraerythrocytic Babesia parasites in all dogs.
      DNA was extracted from the three infected blood samples and an around 410 bp
      portion of the 18S rDNA gene of Babesia species was PCR amplified for subsequent
      molecular characterization. RFLP analysis of the PCR products suggested the
      presence of the species B. vogeli in all infected dogs and sequencing of the PCR
      products from two of the three samples revealed 100% identity among the two
      Turkish isolates. Comparisons with the equivalent 410 bp portions of the 18S rDNA
      gene of Babesia species confirmed the affiliation of these isolates to the B.
      vogeli species. This is the first report and molecular characterization of dog
      infection with a large Babesia species in Turkey.

PMID- 16584844
TI  - Comparison of the reproductive biology between acaricide-resistant and acaricide
      susceptible Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).
AB  - The reproductive fitness of Rhipicephalus (Boophilus) microplus (Canestrini)
      strains resistant to organophosphate (OP), pyrethroid (P), or formamidine (F)
      acaricides was compared to an acaricide-susceptible (SUS) strain to determine
      whether the acquisition of resistance affected reproductive fitness in the
      resistant strains. The SUS strain females had a 3.0 days preoviposition period, a
      12.1 days oviposition period, a 22.5 days egg incubation period, a mean of 3670
      eggs per female, and a mean percentage egg hatch of 78.1%, which were all
      remarkably similar to these same parameters reported for this species throughout
      the world. The reproductive biology of the P-resistant strain (PYR) and the F
      resistant strain (FOR) were, for the most part, similar to those of the SUS
      strain. In the few instances where statistical differences did occur there was
      little evidence that the variation had any biological basis that could be
      attributed to a reduction in fitness related to resistance to P or F acaricides.
      Although the comparison of reproductive parameters of the OP-resistant strain
      (OPR) and the SUS strain identified statistical differences between the mean egg
      incubation and oviposition periods, the magnitude of the differences was not
      sufficient to conclude that the OPR strain was biologically less fit than the SUS
      strain. However, the OPR strain produced 30% fewer eggs (2562 eggs per female)
      than the SUS strain (3670 eggs per female) indicating the acquisition of
      resistance placed the OPR at a selective disadvantage relative to the SUS strain.
      This coupled with a lower, though non-significant, egg hatch was used to predict
      there would be a reduction of at least 34.1% in larval numbers available to
      potentially re-infest subsequent cattle than were available from the SUS strain.
      These data may aid the development of management strategies that can be used to
      control OP-resistant ticks.

PMID- 16584845
TI  - Fatal cytauxzoonosis in a Kentucky cat (Felis domesticus).
AB  - A male domestic shorthair cat was presented with lethargy, anorexia, pyrexia and
      respiratory harshness. Diagnostic clinical chemistries, viral identification and
      tissue fluorescent antibody testing were negative or revealed no underlying
      system failure. Histopathology examination revealed multifocal, variable sized
      and shaped protozoal life forms in the brain, heart, lung, intestine, spleen,
      lymph node and kidney consistent with the intraleukocytic schizonts of Cytauxzoon
      felis.

PMID- 16584846
TI  - The role of glucocorticoids in the uncontrollable stress-induced potentiation of
      nucleus accumbens shell dopamine and conditioned place preference responses to
      morphine.
AB  - Exposure to stressors can impact on the responsiveness to drugs of abuse, and
      glucocorticoid hormones (CORT) may interact with dopamine (DA) within the nucleus
      accumbens shell (NAcs) to mediate these responses. We have previously shown that
      the CORT response to morphine, but not to a previous uncontrollable stressor, is
      necessary for the stress-induced potentiation of morphine's rewarding effects.
      Here, we test (1) the necessity of CORT during inescapable stress (IS) and/or
      morphine for IS potentiation of morphine-induced NAcs DA and (2) the sufficiency
      of enhanced CORT, in the absence of prior IS, to potentiate morphine-induced NAcs
      DA as well as morphine conditioned place preference (CPP) in male Sprague-Dawley
      rats. In the first experiment, we administered the CORT synthesis inhibitors
      metyrapone and aminoglutethimide (100mg/kg each, sc) to suppress the CORT
      response to either IS (100 1 mA tailshocks) or subsequent morphine (3 mg/kg, sc)
      treatment. Twenty-four hour after IS, microdialysis was performed and morphine
      was administered. In the next experiments, CORT (1 mg/kg, sc) was injected 20 or
      30 min before morphine during either microdialysis or CPP testing, respectively,
      in non-stressed rats. We found that IS potentiated subsequent morphine-induced
      NAcs DA and this was completely blocked by CORT suppression before morphine, but
      not before IS. However, elevated levels of CORT concurrent with morphine, but in
      the absence of a stressor, failed to potentiate NAcs DA or CPP. These results
      suggest that the CORT response to morphine is necessary, but not sufficient in
      the absence of prior IS, for sensitized NAcs DA and CPP responding to morphine,
      and provide further evidence that CORT is involved in the expression, but not the
      induction, of this sensitization.

PMID- 16584848
TI  - Normative data on the daily profile of urinary 6-sulfatoxymelatonin in healthy
      subjects between the ages of 20 and 84.
AB  - Although the hormone melatonin is a key factor for the proper functioning of the
      circadian timing system (CTS) and exogenous melatonin has been shown to be
      beneficial in cases of CTS disturbances, a deficit of melatonin has yet to be
      defined as a disorder. The aim of our study was to collect a normative data set
      on 24-h melatonin excretion in healthy human adults living in a natural
      environment. Urine samples were collected from 75 healthy subjects (45 women/30
      men; mean age 47.2, SD 19.5, range 20-84) after five consecutive periods: 2300
      0700, 0700-1100, 1100-1800, 1800-2300 and 2300-0700 h. 6-Sulfatoxymelatonin
      (aMT6s) concentrations were analyzed in duplicate by IBL (Hamburg) using a highly
      sensitive, competitive ELISA kit. Twenty-four hour-aMT6s total amount (rho=-0.68,
      p<0.001), aMT6s nighttime excretion (rho=-0.69, p<0.001), aMT6s morning excretion
      (rho=-0.66, p<0.001) and evening excretion (r=-0.26, p=0.023) were negatively
      associated with age, whereas daytime excretion (r=-0.17, p=0.15) was not. The
      intra-subject night-day ratio varied up to 10.5 (mean 6.0) in young subjects
      (aged 20-35) and up to 5.4 (mean 2.8) in older individuals (age>65). The total
      amount of 24 h-aMT6s (range 7.5-58 microg) as well as the amount of aMT6s
      excreted during the nighttime period (range 327-6.074 ng/h) varied as much as 20
      fold between individuals. Our data show an age-related decline in melatonin
      excretion in healthy subjects living in a natural environment. The high inter
      individual variability of excretion rates may explain why a normative data set is
      of no use in replacement strategies.

PMID- 16584847
TI  - Transactions among adolescent trait and state emotion and diurnal and momentary
      cortisol activity in naturalistic settings.
AB  - In a community sample of 52 adolescents, multilevel growth curve modeling was
      utilized to examine whether within-person changes in momentary mood states, and
      individual differences in trait emotional functioning, were related to adolescent
      cortisol levels in naturalistic settings. Salivary cortisol levels were measured
      seven times a day on two typical weekdays in conjunction with diary reports of
      adolescent mood states. Questionnaire reports of trait emotional functioning
      (depression, anxiety, and anger) were obtained, as were reports of demographic,
      developmental, and health control variables. After accounting for the effects of
      time of day and a wide range of control variables, within-person increases in
      state negative mood (worry/stress and anger/frustration) were significantly
      associated with within-person increases in cortisol. When examining trait
      emotional functioning, adolescents with higher levels of depressive symptoms had
      slightly lower basal cortisol levels, and adolescents with higher levels of trait
      anger had a significantly stronger cortisol response to awakening. Several
      developmental effects were found-adolescents at higher stages of pubertal
      development had daytime basal cortisol curves that were more elevated, had a
      steeper diurnal decline, and showed a lesser cortisol awakening response, and
      cortisol responses to worry/stress increased with age. Cortisol levels were also
      higher at moments adolescents were alone rather than with others, an effect that
      declined significantly with age. Cortisol levels were also higher at moments
      adolescents were alone rather than with others, an effect that declined
      significantly with age. Results suggest that ongoing transactions occur between
      adolescents' everyday emotional experiences and their cortisol levels, and that
      adolescent cortisol activity is modified by age/pubertal stage and by trait
      emotional functioning.

PMID- 16584849
TI  - Lithium and antidepressants: potential agents for the treatment of Rett syndrome.
AB  - Rett syndrome (RTT) is a severe neurodevelopmental disorder occurring almost
      exclusively in females. It is caused by mutations in gene encoding methyl-CpG
      binding protein 2 (MECP2) in the majority of cases. MECP2 was originally thought
      to be a global transcriptional repressor, but recent evidence from studies of
      animals suggests that it may have a role in regulating neuronal activity
      dependent expression of specific genes such as Bdnf. A recent report demonstrated
      that deletion of Bdnf in Mecp2 mutants caused earlier onset/accelerated disease
      progression, whereas BDNF overexpression in the Mecp2 mutant brain led to later
      onset/slower disease progression, suggesting that manipulation of BDNF
      expression/signaling in the brain could be therapeutic for this disease. Lithium
      and antidepressants have been demonstrated to increase central BDNF levels or
      signaling in human as well as animal studies. Thus, it is proposed that these
      agents could have therapeutic potential for RTT subjects. Several points
      regarding the use of these agents in RTT are discussed. Further evaluation of the
      therapeutic effects of these drugs in RTT animal models is needed before clinical
      trials can begin.

PMID- 16584850
TI  - Is systemic hypertension only a sign of chronic sodium chloride intoxication?
AB  - The most important obstacle for preventing hypertension is the belief that
      systemic hypertension has no identifiable cause. This belief, hiding the main
      offender, sodium chloride, causes too much time wasting for combating against
      hypertension. Accepting that sodium chloride is a drug and re-evaluating the
      situation at the light of current pharmacologic rules, it can be possible to get
      rid of the suspicions about the etiologic role of sodium chloride for developing
      systemic hypertension. It is apparent that systemic hypertension is a chronic
      intoxication produced by a drug (sodium chloride) whose dose is between minimal
      and maximal effective dose. Based on epidemiologic studies, minimal effective
      dose of salt, producing hypertension is estimated as 1.76 g/d. This suggests that
      the aim in this context should be removal of table salt from the human diet. Re
      evaluating salt-hypertension relation by means of dose-response relation suggests
      that "salt sensitivity" is a baseless notion, because when the dose is between
      minimal and maximal effective dose, there are a number of individuals which
      respond up or down of any selected level, similar to other drugs. Another
      standpoint of refuting removal of salt is the belief that saltless diet is not
      palatable. According to the self-experiences of the Author, this belief is valid
      only for some time (for a few months), even a few years later saltless meals were
      perceived more palatable. The present paper describes evidences showing that
      systemic hypertension is formed by the chronic exposure to salt and it also
      answers contrary opinions.

PMID- 16584851
TI  - Epoetin alfa improves survival after chemoradiation for stage III esophageal
      cancer: final results of a prospective observational study.
AB  - PURPOSE: This prospective, nonrandomized study evaluates the effectiveness of
      epoetin alfa to maintain the hemoglobin levels at 12 to 14 g/dL (optimal range
      for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and
      its impact on overall survival (OS), metastatic-free survival (MFS), and
      locoregional control (LC). METHODS AND MATERIALS: Ninety-six patients were
      included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week)
      during radiotherapy, which was started at hemoglobin less than 13 g/dL and
      stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT.
      RESULTS: Both groups were balanced for age, sex, performance status, tumor
      length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment
      schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk
      with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of
      hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively
      (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2
      years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not
      significantly different (42% vs. 18% at 2 years, p = 0.09). CONCLUSIONS: The
      findings suggest that epoetin alfa when used to maintain the hemoglobin levels at
      12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

PMID- 16584853
TI  - Inhibition of porcine reproductive and respiratory syndrome virus replication by
      short hairpin RNA in MARC-145 cells.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most
      important contagious agents of swine in the world. The current vaccines cannot
      provide highly effective protection. In this study, the ability of specific short
      hairpin RNA directed against different genomic regions of PRRSV to inhibit virus
      replication in MARC-145 cells was examined. Seven plasmids expressing shRNA
      targeted to GP5 and nucleocapsid (N) protein coding region of PRRSV S1 strain RNA
      were constructed and delivered into MARC-145 cells. After infection, these cells,
      transfected with plasmids pSUPER-N3 or pSUPER-G1, showed a significant decrease
      in virus yield when compared to control cells, by detection using virus titers
      (TCID50), indirect immunofluorescence assay and real-time RT-PCR. The antiviral
      effect was sequence-specific and dose-dependent and could sustain for 96 h.
      Furthermore, by combination of treatment with plasmid pSUPER-N3 and pSUPER-G1,
      the viral inhibition cloud be significantly increased. In addition, the viral
      suppression efficiency by shRNA in previously infected cells was not significant
      different from that induced by shRNA before viral infection. It indicated that
      administration of the two different shRNA could have a synergistic effect. RNA
      interference targeting to the various regions of PRRSV might be a potential
      alternative virus control strategy.

PMID- 16584852
TI  - Pulsed-field gel electrophoresis genotyping of Salmonella gallinarum and
      comparison with random amplified polymorphic DNA.
AB  - Salmonella gallinarum is gram-negative bacteria that cause fowl typhoid (FT) in
      chickens. Since the first outbreak of FT reported in 1992 in Korea, it has widely
      spread throughout the country. Today, FT is one of the most devastating diseases
      of poultry. The aim of the present study was to ascertain a genetic relationship
      among S. gallinarum isolates collected from different regions of Korea over a 10
      year period. We examined a total of 38 isolates of S. gallinarum obtained in 29
      regions of Korea from 1992 to 2001 including the 9R vaccine strain and the
      standard strain of S. gallinarum (ATCC 9184). The PFGE profiles produced 12
      different patterns with the XbaI-digestion and 11 different patterns with the
      SpeI-digestion. The RAPD using URP-6 primers showed eight different genotypes
      with the same Salmonella isolates. The PFGE patterns of the 9R vaccine strain and
      ATCC 9184 of S. gallinarum were different from the identical type A, the most
      common genotype among field isolates in our study. In conclusion, a low genetic
      heterogeneity was observed among Korean S. gallinarum isolates. In addition, PFGE
      appeared to be a more accurate and reproducible method for genotyping of S.
      gallinarum isolates than RAPD.

PMID- 16584854
TI  - Selection of immunodominant mimics of IROMP-99 of rabbit Pasteurella multocida
      from a random 12-peptide library.
AB  - A random 12-peptide library was used to screen immunodominant mimics of 99kDa
      iron-regulated outer membrane protein (IROMP-99) of rabbit Pasteurella multocida.
      In the present study, expression of IROMPs of rabbit P. multocida strain C51-12
      were analyzed by SDS-PAGE, and Western blot to determine the specificity of rat
      antiserum antibodies against IROMP-99. Only IROMP-99 whose expression was induced
      under iron-restricted conditions was detected on nitrocellulose paper. The phage
      display library was screened with rat normal and IROMP-99-specific antiserum. The
      positive phage clones were identified using enzyme-linked immunoadsorbent assay
      (ELISA) and inhibition assays for their reactivity to the antiserum. Out of the
      18 randomly selected positive clones that showed higher reactivity to rat
      antiserum, only ten clones efficaciously inhibited binding of rat antisera to
      IROMPs and their displayed peptides were determined. Alignment using DNAStar
      MegAlign software, results showed that motif WHxTxP was highly conserved among
      nine clones, only clone A7 had no obvious linear homology with either. Our
      findings suggest that the motif WHxTxP could be an immunodominant mimic epitope
      of IROMP-99 of rabbit P. multocida strain C51-12.

PMID- 16584855
TI  - Emitted dose estimates from Seretide Diskus and Symbicort Turbuhaler following
      inhalation by severe asthmatics.
AB  - The dose emitted from dry powder inhalers may be inhalation flow-dependent. Using
      an ex vivo method, the Electronic Lung, we have measured the aerodynamic
      characteristics of the emitted dose for both active constituents from Seretide
      Diskus (salmeterol xinafoate 50 mcg; fluticasone propionate 500 mcg) and
      Symbicort Turbuhaler (formoterol 6 mcg; budesonide 200 mcg). Electronic
      inhalation profiles were collected from 20 severe asthmatics (mean PEFR 53%
      predicted) when they inhaled using a placebo Seretide Diskus and a placebo
      Symbicort Turbuhaler. These were replayed in the Electronic Lung with the
      respective active inhaler in situ. Mean(S.D.) peak inhalation flow rates (PIFR)
      through the Diskus and Turbuhaler were 94.7(32.9) and 76.8(26.2) l min(-1),
      respectively. From the Electronic Lung the Diskus inhalation profiles provided a
      mean(S.D.) fine particle dose (FPD) for fluticasone propionate and salmeterol of
      20.4(4.8) and 18.4(4.4)% labelled dose. For Turbuhaler inhalation profiles the
      FPD was 23.1(12.9) and 20.7(11.1)% labelled dose for budesonide and formoterol,
      respectively. The linear (p < 0.001) relationships between FPD against PIFR for
      budesonide and formoterol were 3 (p = 0.002) and 2.8 (p = 0.007) times steeper
      than fluticasone propionate and salmeterol, respectively. The results highlight a
      more significant effect of inspiratory flow on variable dosage emission when
      using the Symbicort Turbuhaler compared with the Seretide Diskus.

PMID- 16584856
TI  - Development and optimization of a novel sustained-release dextran tablet
      formulation for propranolol hydrochloride.
AB  - A novel oral controlled delivery system for propranolol hydrochloride (PPL) was
      developed and optimized. The in vitro dissolution profiles of sustained-release
      matrix tablets of racemic PPL were determined and compared with the United States
      Pharmacopeia (USP) tolerance specifications for Propranolol Hydrochloride
      Extended-Release Capsules. The influence of matrix forming agents (native
      dextran, hydroxypropyl methylcellulose (HPMC), cetyl alcohol) and binary mixtures
      of them on PPL release in vitro was investigated. A central composite design was
      applied to the optimization of a sustained-release tablet formulation. The
      sustained-release matrix tablets with good physical, mechanical and technological
      properties were obtained with a matrix excipient:PPL ratio of 60:40 (w/w), with a
      dextran:HPMC ratio of 4:1 (w/w) and with a cetyl alcohol amount of 15% (w/w). A
      comparative kinetic study of the present matrix tablets and commercial SUMIAL
      RETARD capsules (Spain) was established. The value for the similarity factor
      (f(2)=69.6) suggested that the dissolution profile of the present two sustained
      release oral dosage forms are similar. Higuchi (diffusion) and Hixon-Crowell
      (erosion) kinetic profiles were achieved and this codependent mechanism of drug
      release was established.

PMID- 16584857
TI  - Immunomodulatory effect of Glossogyne tenuifolia in murine peritoneal macrophages
      and splenocytes.
AB  - Glossogyne tenuifolia Cass., a medicinal plant native to Taiwan, is traditionally
      used as an anti-inflammatory remedy. Oleanolic acid and luteolin-7-glucoside have
      been previously identified as active components of Glossogyne tenuifolia in the
      murine macrophage-like cell line, RAW264.7. Current study investigates the effect
      and mechanism of the ethanol extract of Glossogyne tenuifolia (GT) and its major
      constituents on the release of inflammatory mediators in activated elicited
      murine peritoneal macrophages and splenocytes. Our results showed that GT (up to
      0.15 mg/ml) inhibited the production of proinflammatory mediators, TNF-alpha, IL
      1beta, IL-6, nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in LPS-activated
      macrophages, and IFN-gamma in PHA-activated splenocytes. GT also inhibited LPS
      activated murine iNOS and COX-2 promoter activities in transiently transfected
      RAW264.7 cells. The major constituents, oleanolic acid and luteolin-7-glucoside,
      as well as its aglycone, luteolin, inhibited the release of NO, PGE(2), TNF-alpha
      and IL-1beta in activated peritoneal macrophages. However, only luteolin-7
      glucoside and luteolin were able to reduce IFN-gamma release in PHA-stimulated
      splenocytes. To further investigate the possible mechanisms that interfere with
      LPS- and PHA-signaling, this study focused on nuclear factor-kappaB activation
      signaling pathways. Our results demonstrate that GT (0.075-0.15 mg/ml) treatment
      reduces nuclear factor-kappaB (NF-kappaB) DNA binding activity, as demonstrated
      by electrophoretic mobility shift assay (EMSA). Collectively, the results suggest
      that GT inhibits proinflammatory mediator synthesis in activated murine
      peritoneal macrophages and splenocytes, in part through NF-kappaB-dependent
      pathways.

PMID- 16584858
TI  - Role of mangiferin on biochemical alterations and antioxidant status in
      isoproterenol-induced myocardial infarction in rats.
AB  - The current study dealt with the protective role of mangiferin, a polyphenol from
      Mangifera indica Linn. (Anacardiaceae), on isoproterenol (ISPH)-induced
      myocardial infarction (MI) in rats through its antioxidative mechanism.
      Subcutaneous injection of ISPH (200 mg/kg body weight in 1 ml saline) to rats for
      2 consecutive days caused myocardial damage in rat heart, which was determined by
      the increased activity of serum lactate dehydrogenase (LDH) and creatine
      phosphokinase isoenzymes (CK-MB), increased uric acid level and reduced plasma
      iron binding capacity. The protective role of mangiferin was analyzed by
      triphenyl tetrazolium chloride (TTC) test used for macroscopic enzyme mapping
      assay of the ischemic myocardium. The heart tissue antioxidant enzymes such as
      superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase
      and glutathione reductase activities, non-enzymic antioxidants such as
      cerruloplasmin, Vitamin C, Vitamin E and glutathione levels were altered in MI
      rats. Upon pretreatment with mangiferin (100 mg/kg body weight suspended in 2 ml
      of dimethyl sulphoxide) given intraperitoneally for 28 days to MI rats protected
      the above-mentioned parameters to fall from the normal levels. Activities of
      heart tissue enzymic antioxidants and serum non-enzymic antioxidants levels rose
      significantly upon mangiferin administration as compared to ISPH-induced MI rats.
      From the present study it is concluded that mangiferin exerts a beneficial effect
      against ISPH-induced MI due to its antioxidant potential, which regulated the
      tissues defense system against cardiac damage.

PMID- 16584859
TI  - Adenoviral mediated MyoD gene transfer into fibroblasts: myogenic disease
      diagnosis.
AB  - MyoD, a master regulatory gene for myogenesis, converts mesoderm derived cells to
      the skeletal muscle phenotype MyoD gene transfer into skin fibroblasts has been
      attempted in an effort to diagnose genetic muscle diseases. Although the gene
      transduction efficiency of adenoviral gene delivery systems is higher than that
      of various other systems, the rate of myo-conversion is insignificant. Since high
      adenovirus doses are cytotoxic and exogenous MyoD expression is insufficient for
      skin fibroblasts to re-differentiate into muscle cells, we constructed the novel
      adeno-MyoD vector, Ad.CAGMyoD using the recombinant CAG promoter. Even at a lower
      multiplicities of infection most skin fibroblasts infected with Ad.CAGMyoD could
      convert into myotubes without vector-induced cytotoxicity. The converted cells
      expressed muscle-specific desmin and full-length dystrophin, both of which were
      detected by Western blotting. Genetic and immunohistochemical analyses using skin
      fibroblasts and our vector system are reliable and useful for the clinical
      diagnosis of genetic muscle diseases.

PMID- 16584860
TI  - [Oxidatif-stress and COPD. Role of infection. Prevention].
AB  - For the next decade, COPD will become the third cause of mortality in the world.
      COPD is mainly due to cigarette smoking and presents different levels of severity
      according to people, probably linked to environmental and genetic factors, which
      are not well documented. Recent publications pointed out bacterial bronchial
      colonization and exacerbations of infectious origin as worsening factors through
      a pro-inflammatory effect and oxidative stress. This should lead to a
      comprehensive review of anti-infectious prevention tools and to discuss the role
      of prophylactic antibiotherapy and antioxidants.

PMID- 16584861
TI  - Recent aging research in Caenorhabditis elegans.
AB  - Evidence gathered over the past 15 years shows that the nematode Caenorhabditis
      elegans is excellently suited as a model to study aging processes in the entire
      organism. Genetic approaches have been used to identify and elucidate multiple
      mechanisms and their corresponding genes that limit the life span of C. elegans.
      These highly conserved pathways include the well-studied insulin/IGF-1 receptor
      like signaling pathway, which is thought to be a central determinant of life
      span, since several other mechanisms depend or converge on the insulin/IGF-1
      pathway transcription factor DAF-16/FoxO. In this review we focus on new insights
      into the molecular mechanisms of aging in C. elegans, including new genes acting
      in the insulin/IGF-1 pathway and germline signaling. In addition, stress response
      pathways and mitochondrial mechanisms, dietary restriction, SIR2 deacetylase
      activity, TOR and TUBBY signaling, as well as telomere length contribution are
      discussed in relation to recent developments in C. elegans aging research.

PMID- 16584862
TI  - Occurrence of rhizobia in the gut of the higher termite Nasutitermes nigriceps.
AB  - Wood-eating termites feed on a diet highly deficient in nitrogen. They must
      complement their diet with the aid of nitrogen-fixing bacteria. Nitrogen fixation
      in the gut has been demonstrated, but information about nitrogen-fixing bacteria
      in pure culture is scarce. From the higher termite Nasutitermes nigriceps the
      symbiotic bacterial strain M3A was isolated, which thrives in the hindgut
      contents. The Gram-negative strain exhibited similarities to the species of the
      genus Ensifer (including Sinorhizobium) on the basis of morphological and
      physiological/biochemical features. The 16S rRNA gene analysis showed the highest
      sequence similarity of the isolate M3A to Ensifer adhaerens (>99%; ATCC 33499).
      The DNA-DNA hybridization revealed a similarity of 66% with E. adhaerens
      (NCIMB12342(T)). In contrast to the type strain the isolate M3A possesses the
      capacity to nodulate plant roots. This is the first report on the detailed
      identification of a rhizobia-related strain from the intestinal tract of animals.
      Strain M3A has been deposited with two culture collections (DSM10169; ATCC BAA
      396).

PMID- 16584863
TI  - Taxonomic characterization of members of the genus Corallococcus: molecular
      divergence versus phenotypic coherency.
AB  - Corallococcus coralloides DSM 2259(T), Corallococcus exiguus DSM 14696(T),
      Corallococcus macrosporus DSM 14697(T) and more than 35 strains identified as
      members of Corallococcus on the basis of morphology were subjected to partial
      sequences analysis of three housekeeping genes (lepA, fusA and rpoB),
      complementing a recent phylogenetic analysis based on genes coding for 16S rRNA
      and gyrB. Phylogenetic analysis of each gene, generated by maximum likelihood and
      two different additive treeing algorithms, resulted in the separate position of
      C. macrosporus DSM 14697(T) and a few Corallococcus strains that were more
      closely related to Myxococcus xanthus than to the other members of Corallococcus.
      The latter strains formed three clearly separate clusters by 16S rRNA gene
      phylogeny. This relationship, however, was only partially recovered by the other
      gene trees. Group 1, embracing the type strains of C. coralloides and C. exiguus,
      only emerged as a coherent cluster in the 16S rRNA gene tree. In all other gene
      trees this cluster embraced organisms of cluster 3, which either formed coherent
      subclusters (gyrB, lepA) or which appeared polyphyletic (fusA, rpoB). Group 2
      organisms consistently constituted a monophyletic cluster, though their branching
      within the gene trees differed. A concatenated tree, based on the analysis of
      about 5400 nucleotides of all five partial genes was most similar to the 16S rRNA
      gene tree. In order to determine whether the individual clusters that emerged by
      16S rRNA gene analysis (>99.1% intracluster similarities) show phenetic
      properties that would allow their description as new species, a few strains of
      each group were subjected to the analysis of whole cell fatty acid and
      physiological properties. Riboprint patterns were generated for some members of
      group 1. While the DNA-DNA reassociation values and riboprint patterns confirmed
      the genomic heterogeneity of members of cluster 1, none of the other properties
      investigated were sufficiently discriminative to allow the formal description of
      strain clusters as new species.

PMID- 16584864
TI  - Controlling ethylene responses in flowers at the receptor level.
AB  - For a vast number of ornamental species, blocking the plant's response to
      ethylene is an efficient strategy to enhance the longevity of the flowers. The
      most effective ways to conduct such interference will be reviewed in this paper.
      A large number of chemical compounds have been evaluated for their effects on
      ethylene production and perception. Among these are a range of strained olefines.
      This has resulted in the discovery that cyclopropenes, among them 1
      methylcyclopropene (1-MCP) and a number of other substituted cyclopropenes
      effectively block ethylene responses at the receptor level. A lot of testing
      remains to be done to uncover the full potential of these compounds, but they do
      offer promising new ways to extend the postharvest life of ornamentals. Also
      genetic modification appears to be a very effective way in controlling of
      ethylene synthesis and perception. Attempts to use both a reduced endogenous
      ethylene production and a reduced sensitivity to ethylene will be reviewed. Among
      these the use of the mutant ethylene receptor gene, etr1-1, from Arabidopsis
      seems most promising, especially when it is expressed under the control of a
      flower specific promoter.

PMID- 16584865
TI  - The detection of oesophageal adenocarcinoma by serum microsatellite analysis.
AB  - BACKGROUND AND AIMS: Organ-confined oesophageal cancer in an early stage can be
      cured in many patients, whereas more extensive lesions have a poor prognosis. We
      sought to develop a non-invasive test for cancer detection and evaluation of the
      prognosis of the patients by using a novel molecular approach. MATERIAL AND
      METHODS: Matched normal-, tumour- and serum-samples were obtained from 32
      patients with adenocarcinoma of the oesophagus. DNA was extracted and the samples
      were subjected to microsatellite analysis using 12 markers. Serum and normal
      samples from 10 healthy individuals served as controls. RESULTS: Twenty-seven of
      the 32 patients (84.4%) with malignant tumours were found to have one or more
      microsatellite DNA alterations in their primary tumour. Twenty-six of the 32
      patients (81.3%) had alterations in the serum by microsatellite analysis.
      Interestingly, all patients without lymphatic metastasis and three early
      carcinomas (pT1pN0) already displayed LOH alteration in the serum, while all
      serum DNA of samples from normal control subjects were negative. Survival was not
      significantly correlated with either LOH in the tumour or LOH in the serum.
      CONCLUSION: These data suggest that microsatellite DNA analysis in serum
      specimens might provide a potentially valuable tool for early detection of
      oesophageal cancer. The evidence of circulating tumour DNA reflects the
      propensity of these tumours to spread to distant sites. Up to now the follow-up
      is still too short to draw further conclusions on the prognostic impact of this
      finding.

PMID- 16584866
TI  - Thyroid hormones in relation to urinary metabolites of non-persistent
      insecticides in men of reproductive age.
AB  - Human exposure to contemporary-use insecticides is widespread, but effects of
      exposure on human endocrine function have gone largely untested to date. Samples
      of urine and blood were collected concurrently from 322 adult men between the
      years 2000 and 2003. Urine samples were analyzed for 3,5,6-trichloro-2-pyridinol
      (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, and 1-napththol
      (1N), a metabolite of carbaryl and naphthalene. Serum samples were analyzed for
      free T(4), total T(3), and thyroid stimulating hormone (TSH). There was an
      association between TCPY and TSH, where an interquartile range (IQR) increase in
      TCPY was associated with a 9% (95% confidence interval 0-18%) increase in TSH.
      There was also a suggestive inverse association between TCPY and free T(4). There
      were no associations between 1N and thyroid hormones. Environmental exposure to
      chlorpyrifos, chlorpyrifos-methyl, or its metabolite TCPY may be associated with
      altered thyroid function in human males.

PMID- 16584867
TI  - Detection of cytotoxic CD13-specific autoantibodies in sera from patients with
      ulcerative colitis and Crohn's disease.
AB  - Recent evidence suggests an association between inflammatory bowel disease (IBD)
      and human cytomegalovirus (HCMV) infection, but the exact pathogenic role of HCMV
      in this disease remains unclear. HCMV infection has for a long time been known to
      be associated with various autoimmune manifestations and the formation of
      autoantibodies. Previous studies from our group have shown that HCMV is
      associated with a human protein, CD13 (aminopeptidase N) and that autoantibodies
      against this protein are frequently found in HCMV infected bone marrow transplant
      patients with chronic graft versus host disease. We have recently observed that
      90% of IBD patients have an active HCMV infection. In this study, we examined the
      presence and cytotoxicity of CD13-specific autoantibodies in sera obtained from
      28 patients with ulcerative colitis and 26 patients with Crohn's disease, and in
      sera obtained from healthy blood donors by using flow cytometric assays against
      mouse cells transfected with human CD13 or a microcytotoxicity assay against
      different CD13 positive human cells. Cytotoxic CD13-specific autoantibodies were
      identified in 66% of the sera obtained from HCMV-IgG positive patients with
      ulcerative colitis and in 58% of the sera obtained from HCMV-IgG positive
      patients with Crohn's disease, but not in control individuals. These cytotoxic
      autoantibodies may interfere with biological cell functions and could thereby
      contribute to the chronic inflammation in patients with IBD.

PMID- 16584868
TI  - Alveolar cleft osteoplasty using tissue-engineered osteogenic material.
AB  - The use of tissue-engineered osteogenic material comprising platelet-rich plasma
      and autologous mesenchymal stem cells isolated, expanded and induced to
      osteogenic potential in bone augmentation procedures as a replacement for
      autologous bone grafts, offers predictable results with minimal donor-site
      morbidity. This material was applied for an alveolar cleft osteoplasty of a 9
      year-old female patient. Serial computed tomograms showed the regenerated bone
      extending from the cleft walls after 3 months and bridging the cleft after 6
      months, with 79.1% of the grafted region after 9 months at the time when the
      canine and lateral incisor in the affected side erupted in the reconstructed
      alveolar ridge.

PMID- 16584869
TI  - The early use of a perforator flap of the lateral lower limb in maxillofacial
      reconstructive surgery.
AB  - The development of perforator-based flaps led to new donor sites and enlarged the
      spectrum of recipient vessels using arteries and veins of very small calibres.
      Although these flaps, which are directly anastomosed at their terminal cutaneous
      branches, are becoming more and more important for reconstructions in other
      regions of the body, perforator-based flaps have not played an important role in
      maxillofacial surgery until now. This study reports the experience with 24
      consecutive perforator flaps from the lateral lower limb for intra- and extraoral
      defect coverage. Septo- or myoseptocutaneous perforators from the peroneal artery
      served as the flap pedicle having a length of 4-7 cm and diameters of 1-2 mm.
      Indications were reconstructions of the floor of the mouth (10), soft palate (3),
      tongue (6), closure of perforating cheek defects (2) and reconstruction of the
      facial skin (3). Anastomoses were performed to the lingual, facial, temporal or
      thyroid superior artery. Except for 2 cases, all perforator-based flaps were
      healed well and the morbidity of the donor site was nearly negligible. According
      to the early experience in this study, perforator-based flaps from the lateral
      lower limb may have an indication if recipient vessels available are close to the
      defect and if very low donor site morbidity is important to the patient.

PMID- 16584870
TI  - Limited regression of central giant cell granuloma by interferon alpha after
      failed calcitonin therapy: a report of 2 cases.
AB  - Central giant cell granuloma (CGCG) is a benign lesion of the jaws with a
      sometimes locally aggressive behaviour. The most common therapy is surgical
      curettage which has a high recurrence rate, especially in lesions with aggressive
      signs and symptoms (i.e. pain, paresthesia, root-resorption and rapid growth).
      Alternative therapies such as interferon alpha (INFalpha) or calcitonin are
      described in the literature. In this study 2 patients with an aggressive CGCG are
      presented who were treated with INF mono-therapy. INF mono-therapy was capable of
      terminating the rapid growth of the lesion in both patients and induced a partial
      reduction. Total resolution, however, was not obtained and alternative treatment
      is still necessary.

PMID- 16584871
TI  - Three-dimensional high-inductance birdcage coil for NQR applications.
AB  - A birdcage coil capable of operating simultaneously and independently in three
      orthogonal dimensions has been developed. A co-rotational end-ring mode producing
      an RF field in the longitudinal direction was utilized in addition to the two
      common transverse orthogonal modes. Two conductor turns were used for each of the
      coil's windows, increasing its inductance by a factor of four, thereby, making
      the coil suitable for low-frequency applications. Two or three-frequency
      detection can be easily carried out with this device. Orthogonality of the coil's
      channels allows arbitrarily close frequency positioning of each resonant mode,
      potentially useful in wide-line NQR studies, in which simultaneous
      excitation/detection of signals from three adjacent regions of a single wide line
      can be performed. The coil's performance was evaluated using a three-dimensional
      scheme, in which a circularly polarized experiment was combined with a linearly
      polarized measurement at another frequency, resulting in SNR improvement by 55%.

PMID- 16584872
TI  - Bis(trimethoxysilylpropyl)amine and tetraethoxysilane derived gels as effective
      controlled release carriers for water-soluble drugs of small molecules.
AB  - The controlled release of sodium salicylate (SS) from the gels derived from
      bis(trimethoxysilylpropyl)amine (TSPA) or the mixture of TSPA with
      tetraethoxysilane (TEOS) was investigated. The experimental results suggest that
      the release of SS can be easily controlled by adjusting the ratio between TSPA
      and TEOS. Increasing the ratio between TSPA and TEOS lowers the surface area and
      pore volume of the gels, while enhances the interactions between the drug and the
      gel matrix. Therefore, reduces the release rate of the drug effectively. The
      overall release process is found to be diffusion controlled, and the release
      behavior can be well explained by considering the effects of the textual
      properties of the gels and the interactions between the drug and the gel matrix.
      TSPA is found to be a very convenient and effective precursor for the preparation
      of gels for controlled release of both hydrophilic and hydrophobic drugs,
      especially water-soluble drugs of small molecules.

PMID- 16584873
TI  - Animal models of asthma: innovative methods of lung research and new
      pharmacological targets.
AB  - Allergic diseases like bronchial asthma are increasing in societies with western
      lifestyle. In the last years substantial progress was made in the understanding
      of the underlying mechanisms and explanations like the hygiene hypothesis were
      developed. However the exact mechanisms of the physiological and immunological
      events in the lung leading to bronchial asthma are still not fully understood.
      Therefore, animal models of asthma have been established and improved to study
      the complex cellular interactions in vivo. Since mice became the most frequently
      used animal species the methods for detecting lung physiology, e.g. lung function
      measurements were adapted to the small size of the murine lung. Laser-dissection
      and precision cut lung slices have become common techniques to get a view into
      distinct lung compartments and cells. In addition genomic and proteomic
      approaches are now used widely. On the other hand a major conclusion of the
      workshop stated that more than one species is necessary in research and for
      pharmacological screening in asthma and COPD. The resulting new understanding in
      the mechanisms of asthma pathogenesis has lead to a rapid identification of novel
      pharmaceutical targets for treatment of the disease.

PMID- 16584874
TI  - Differential expression of the neurotrophin receptors p75NTR, TrkA, TrkB and TrkC
      in human peripheral blood mononuclear cells.
AB  - Neurotrophins are involved in the pathogenesis of allergic asthma. In addition to
      their influence on afferent sensory nerves within the lung, it has been shown in
      the last years that these factors modulate allergic airway inflammation. The
      knowledge about their immunomodulatory roles on diverse subsets of immune cells
      is still fragmentary and incomplete. Since neurotrophin receptor surface
      expression is essential for neurotrophin action, the aim of our study was to
      systematically investigate the expression pattern of the low affinity pan
      neurotrophin receptor p75NTR as well as the high-affinity receptors TrkA, TrkB
      and TrkC in human peripheral blood mononuclear cells. Our results show that each
      of the receptors has an individual expression pattern in diverse immune cell
      subtypes. However, there were no differences in neurotrophin receptor expression
      in healthy controls and patients with allergies.

PMID- 16584875
TI  - Mineralized cartilage in the skeleton of chondrichthyan fishes.
AB  - The cartilaginous endoskeleton of chondrichthyan fishes (sharks, rays, and
      chimaeras) exhibits complex arrangements and morphologies of calcified tissues
      that vary with age, species, feeding behavior, and location in the body.
      Understanding of the development, evolutionary history and function of these
      tissue types has been hampered by the lack of a unifying terminology. In order to
      facilitate reciprocal illumination between disparate fields with convergent
      interests, we present levels of organization in which crystal orientation/size
      delimits three calcification types (areolar, globular, and prismatic) that
      interact in two distinct skeletal types, vertebral and tessellated cartilage. The
      tessellated skeleton is composed of small blocks (tesserae) of calcified
      cartilage (both prismatic and globular) overlying a core of unmineralized
      cartilage, while vertebral cartilage usually contains all three types of
      calcification.

PMID- 16584876
TI  - Analysis of fracture healing by large-scale transcriptional profile identified
      temporal relationships between metalloproteinase and ADAMTS mRNA expression.
AB  - The aim of this study was to validate the use of transcriptional profiling as a
      means of characterizing the complex interactions of the thousands of genes that
      are expressed during fracture healing. Standard mid-diaphyseal tibia fractures
      were generated in C57/B6 murine tibiae and the transcriptional expression of
      approximately 13,000 genes was assessed. Three time points after fracture were
      assessed: day 3, representative of the inflammatory phase; day 10, representative
      of the peak of cartilage formation; and day 21, representative of the period of
      primary bone formation and coupled remodeling. A self-organizing mapping approach
      of the data revealed the temporal relationships between the expression of mRNAs
      for extracellular matrix proteins and the proteases that degrade the proteoglycan
      and collagenous matrices. A broad group of extracellular matrix protein mRNAs
      representative of basement membranes, blood vessels and cartilage all showed
      elevated expression over the first 21 days of fracture healing. The sorting of
      the data identified an orderly temporal expression of the metalloproteinases and
      ADAMTS during the progression of fracture healing with (MMP2/MMP14/TIMP2) and
      ADAMTS4 and 15 preceding the expression of (MMP9/MMP13). Based on their patterns
      of expression, relative to the known activities of the encoded proteolytic
      enzymes, our results suggest that the dissolution of cartilage protoeglycans
      proceeds before the underlying collagenous components of the matrix are removed.
      The exclusion of several mRNAs that are normally expressed by osteoclasts in the
      profiles of mRNAs from days 3 and 10 suggests that osteoclastic activity was
      largely absent during the early periods of cartilage tissue formation and that
      proteoglycan and specific collagenase activities, precedes or is prerequisite to
      later osteoclast infiltration into the remodeling tissues.

PMID- 16584877
TI  - Association between dietary fat and antioxidant status of Tunisian type 2
      diabetic patients.
AB  - BACKGROUND: The antioxidant enzymes: superoxide dismutase (Cu/Zn SOD) and
      glutathione peroxidase (GSH-Px) provide a defense against the damage of cells by
      reactive oxygen species, which increased in diabetic state. It was demonstrated
      that dietary treatment could improve the antioxidant status in patients with type
      2 diabetes mellitus. This study was undertaken to determine if erythrocyte Cu/Zn
      SOD and GSH-Px activities correlate with dietary nutrients in 35 selected type 2
      diabetic patients (21 women and 14 men) without diabetic complications. RESULTS:
      We found that erythrocyte Cu/Zn SOD was diminished in patients with poor
      controlled diabetes and GSH-Px activity was significantly decreased in obese
      compared with non-obese type 2 diabetic patients (1.07+/-0.87 and 2.36+/-1.99
      U/ml, respectively; P=0.024). Both erythrocyte Cu/Zn SOD and GSH-Px activities
      were positively correlated to erythrocyte omega3-polyunsaturated fatty acids
      (PUFA). In non-obese diabetic patients, only GSH-Px activity was correlated
      negatively to the fraction of linoleic acid (18:2omega6) and arachidonic acid
      (20:4omega6) in erythrocytes phospholipids. CONCLUSIONS: The data of this study
      reveal that activities of erythrocyte antioxidant enzymes were altered in type 2
      diabetic patients. Further studies are needed to determine if diet supplemented
      with omega3-PUFA is required to improve antioxidant defense system in diabetic
      state.

PMID- 16584878
TI  - Routine use of pleural fluid cultures. Are they indicated? Limited yield, minimal
      impact on treatment decisions.
AB  - In pleural infection, it has been recommended that Gram stain and cultures should
      be obtained on a routine basis. However, this recommendation has not been tested
      prospectively. We evaluated the yield of microbiological studies in 259 patients
      with parapneumonic pleural effusion. Microbiological studies were positive on the
      pleural fluid of 50 patients (19.3%). In 48 of the 50 patients with positive
      microbiological results (96%), the need for pleural drainage was correctly
      predicted by pleural fluid parameters. There were no differences in hospital stay
      (9.5+/-2.5 days versus 9.9+/-3.2 days, P=0.68) or in mortality (2 deaths in each
      group, P=0.58) between the group of patients in which antibiotic treatment was
      changed according to microbiological results and the group of patients in which
      it is not. In conclusion, this study demonstrates that, at least in our
      institution, routine microbial investigation of pleural fluid adds very little to
      the standard management of parapneumonic effusions.

PMID- 16584879
TI  - Malignant pleural mesothelioma: occupational and environmental exposure.

PMID- 16584881
TI  - Exhaled nitric oxide as a diagnostic test for asthma in rhinitic patients with
      asthmatic symptoms.
AB  - BACKGROUND: Rhinitis is a major risk factor for asthma, so that evaluation of the
      lower airways is recommended in patients with rhinitis. Exhaled nitric oxide
      (FE(NO)) is considered a marker of airway inflammation and it has been found to
      be useful for the screening of patients with suspected diagnosis of asthma. Our
      aim was to assess the validity and accuracy of FE(NO) to identify patients with
      asthma in 48 non-smoking patients with persistent rhinitis and asthma-like
      symptoms. METHODS: Asthma was diagnosed on the basis of 12% improvement in FEV1
      after salbutamol or a methocholine PD(20)FEV1<800 microg. Prior to lung function
      FE(NO) was measured with the single exhalation method at 50 ml/s. RESULTS: The
      geometric mean (95% confidence interval) FE(NO) was significantly higher in the
      18/48 asthmatics than in the non-asthmatic patients (60 ppb, CI 95%: 50-89,
      versus 30 ppb, CI 95%: 28-45, P=0.001). Receiver operating characteristic (ROC)
      curve for the diagnosis of asthma indicated that FE(NO) is an acceptable
      discriminator between patients with and without asthma (area under the ROC
      curve=0.78). None of the asthmatic patients had FE(NO) values<25 ppb and all the
      patients with FE(NO)>100 ppb (n=5) were asthmatics. The sensitivity and
      specificity of FE(NO) for detecting asthma, using 36 ppb as cut-off point, were
      78% and 60% and the positive and negative predictive values were 54% and 82%,
      respectively. CONCLUSIONS: Measuring FE(NO) may be useful for the screening of
      rhinitic patients with asthma-like symptoms.

PMID- 16584880
TI  - Acute exacerbation of interstitial pneumonia following surgical lung biopsy.
AB  - STUDY OBJECTIVES: Surgical lung biopsy (SLB) plays an important role in the
      diagnosis of interstitial pneumonia, however, the occurrence of acute respiratory
      failure following SLB remains largely unreported. We evaluated the incidence,
      clinical features, therapy and prognosis of acute exacerbation of interstitial
      pneumonia following SLB. DESIGN: Retrospective study of consecutive patients who
      underwent SLB to establish a diagnosis of diffuse lung disease between May 1989
      and April 2000. Patients with an acute exacerbation following lung biopsy were
      studied, and the HRCT images of the chest before and after surgery were reviewed.
      MEASUREMENTS AND RESULTS: Among the 236 consecutive patients with interstitial
      pneumonia who underwent a surgical lung biopsy, five (2.1%) (IPF, 3; NSIP, 1;
      COP, 1) developed acute exacerbation of the diffuse lung disease in the course of
      1-18 days after SLB. The extent of parenchymal involvement on HRCT before surgery
      was not significantly different between operated and contralateral nonoperated
      lung. Significantly increased regions of parenchymal involvement on HRCT were
      seen postoperatively compared with the preoperative CT in both the operated
      (20.7+/-12.5% versus 38.2+/-10.8%, P = 0.0431) and nonoperated lung (22.7+/-13.8%
      versus 70.5+/-24.4%, P = 0.0431), but the extent of the parenchymal involvement
      was significantly greater on the nonoperated side (P = 0.0251). Two of the 3 IPF
      patients died from the acute exacerbation. CONCLUSIONS: It is important to be
      aware of the possibility of acute exacerbation of interstitial pneumonia
      following SLB even after an apparently uneventful immediate postoperative course.
      The asymmetric image findings suggest that intraoperative respiratory management
      is a possible etiologic factor.

PMID- 16584883
TI  - Arabidopsis BRICK1/HSPC300 is an essential WAVE-complex subunit that selectively
      stabilizes the Arp2/3 activator SCAR2.
AB  - The actin cytoskeleton dynamically reorganizes the cytoplasm during cell
      morphogenesis. The actin-related protein (Arp)2/3 complex is a potent nucleator
      of actin filaments that controls a variety of endomembrane functions including
      the endocytic internalization of plasma membrane , vacuole biogenesis , plasma
      membrane protrusion in crawling cells , and membrane trafficking from the Golgi .
      Therefore, Arp2/3 is an important signaling target during morphogenesis. The
      evolutionarily conserved Rac-WAVE-Arp2/3 pathway links actin filament nucleation
      to cell morphogenesis . WAVE translates Rac-GTP signals into Arp2/3 activation by
      regulating the stability and/or localization of the activator subunit Scar/WAVE .
      The WAVE complex includes Sra1/PIR121/CYFIP1, Nap1/NAP125, Abi-1/Abi-2,
      Brick1(Brk1)/HSPC300, and Scar/WAVE : Defining the in vivo function of each
      subunit is an important step toward understanding this complicated signaling
      pathway. Brk1/HSPC300 has been the most recalcitrant WAVE-complex protein and has
      no known function. In this paper, we report that Arabidopsis brick1 (brk1) is a
      member of the "distorted group" of trichome morphology mutants, a group that
      defines a WAVE-ARP2/3 morphogenesis pathway . In this paper we provide the first
      strong genetic and biochemical evidence that BRK1 is a critical WAVE-complex
      subunit that selectively stabilizes the Arp2/3 activator SCAR2.

PMID- 16584882
TI  - Carbon nanotubes-polymer-redox mediator hybrid thin film for electrocatalytic
      sensing.
AB  - Electrocatalytic sensing of NADH using a hybrid thin film derived from multi-wall
      carbon nanotubes (CNTs), Nafion (Nf) polymer and electrogenerated redox mediator
      is described. The redox mediator was electrochemically generated by the oxidation
      of serotonin on the hybrid thin film modified glassy carbon electrode (GC/Nf
      CNT). Controlled potential electrolysis of serotonin at 0.1 V in neutral solution
      results in the generation of the redox mediator 5,5'-dihydroxy-4,4'-bitryptamine
      (DHB) on the hybrid thin film. The electrogenerated DHB has redox active quinone
      imine structure and was electrochemically characterized by studying the pH
      dependent redox response. DHB on the hybrid thin film exhibits reversible redox
      peak at -0.05 V and the formal potential shifts by -55 mV while increasing the
      solution pH by 1 unit. The quinone-imine structure of DHB efficiently catalyzes
      the oxidation of NADH with a decrease in the overpotential of about 500 mV
      compared to the unmodified electrode. The CNTs of the hybrid thin film
      facilitates the mediated electrocatalytic oxidation of NADH. The hybrid thin film
      modified electrode exhibits stable amperometric response and it linearly responds
      to NADH (0.5-400 microM). This hybrid thin film modified electrode could detect
      NADH as low as 0.1 microM at -0.05 V with a sensitivity of 11.1 nA/microM in
      physiological pH.

PMID- 16584884
TI  - Integron-sequestered dihydrofolate reductase: a recently redeployed enzyme.
AB  - The introduction and wide use of antibacterial drugs has resulted in the
      emergence of resistant organisms. DfrB dihydrofolate reductase (DHFR) is a
      bacterial enzyme that is uniquely associated with mobile gene cassettes within
      integrons, and confers resistance to the drug trimethoprim. This enzyme has
      intrigued microbiologists since it was discovered more than thirty years ago
      because of its simple structure, enzymatic inefficiency and its virtual
      insensitivity to trimethoprim. Here, for the first time, a comprehensive
      discussion of genetic, evolutionary, structural and functional studies of this
      enzyme is presented together. This information supports the ideas that DfrB DHFR
      is a poorly adapted catalyst and has recently been recruited to perform a novel
      enzymatic activity in response to selective pressure.

PMID- 16584885
TI  - Assembling the bacterial segrosome.
AB  - Genome segregation in prokaryotes is a highly ordered process that integrates
      with DNA replication, cytokinesis and other fundamental facets of the bacterial
      cell cycle. The segrosome is the nucleoprotein complex that mediates DNA
      segregation in bacteria, its assembly and organization is best understood for
      plasmid partition. The recent elucidation of structures of the ParB plasmid
      segregation protein bound to centromeric DNA, and of the tertiary structures of
      other segregation proteins, are key milestones in the path to deciphering the
      molecular basis of bacterial DNA segregation.

PMID- 16584886
TI  - Activity measurements of the high-energy pure beta-emitters 89Sr and 90Y by the
      TDCR efficiency calculation technique.
AB  - The absolute activities of the pure beta-emitters 89Sr and 90Y have been
      determined by a direct method, namely the triple-to-double coincidence ratio
      (TDCR) efficiency calculation technique. This undertaking has extended further
      the number of radionuclides that have been standardized by this non-extrapolation
      liquid scintillation (LS) method. Both measurements were carried out within the
      framework of international key comparisons under the auspices of the
      International Bureau of Weights and Measures (BIPM). The TDCR results agreed well
      with those of other participating national laboratories, most using alternative
      (tracer) methods.

PMID- 16584887
TI  - Interleukin-2 in human milk: a potential modulator of lymphocyte development in
      the breastfed infant.
AB  - Development of lymphocyte subpopulations and response to antigen exposure will be
      influenced by the limited ability of neonates to produce cytokines. In the case
      of cytokines such as interleukin (IL)-2 which are potent T lymphocyte regulators
      but poorly produced by newborn infants, the supply of cytokines through human
      milk could alleviate an immunological deficit and potentially aid the maturation
      of the immune system. We analysed human milk from 52 mothers (15-357 days
      postpartum) by ELISA to determine levels of aqueous IL-2, as well as production
      by human milk cells. IL-2 was detectable (>8 pg/mL) in the aqueous phase of 81%
      of all day 1 samples with no significant difference found in the mean
      concentration over 3 consecutive days. IL-2 was produced constitutively at
      detectable levels by 57% of milk cell samples and production was significantly
      increased by stimulation with Con A (380%). No correlation was found between
      aqueous and cellular IL-2, however there was a significant correlation between
      milk aqueous IL-2 and serum IL-2. This is the first report of IL-2 in the aqueous
      phase of human milk. A supply of exogenous IL-2 in human milk may provide the
      suckling infant with important immunological signals during a significant stage
      of T cell development.

PMID- 16584888
TI  - Montelukast protects against renal ischemia/reperfusion injury in rats.
AB  - BACKGROUND: Oxygen free radicals are important components involved in the
      pathophysiological processes observed during ischemia/reperfusion (I/R).
      OBJECTIVE: This study was designed to assess the possible protective effect of
      montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (CysLT1),
      on renal I/R injury. METHODS: Wistar albino rats were unilaterally nephrectomized
      and subjected to 45 min of renal pedicle occlusion followed by 6 h of
      reperfusion. Montelukast (10 mgkg(-1), i.p.) or saline was administered at 15 min
      prior to ischemia and immediately before the reperfusion period. At the end of
      the reperfusion period, following decapitation, kidney samples were taken for
      histological examination or for determination of renal malondialdehyde (MDA), an
      end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and
      myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration.
      Formation of reactive oxygen species in renal tissue samples was monitored by
      using chemiluminescence (CL) technique with luminol and lucigenin probes.
      Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were
      measured in the serum samples, while leukotriene B4, TNF-alpha, IL-beta, IL-6 and
      total antioxidant capacity (AOC) were assayed in plasma samples. RESULTS:
      Ischemia/reperfusion caused a significant decrease in renal GSH and plasma AOC,
      which was accompanied with significant increases in MDA level, MPO activity, and
      CL levels of the renal tissue concomitant with increased levels of the pro
      inflammatory mediators, LDH activity, creatinine and BUN. On the other hand,
      montelukast treatment reversed all these biochemical indices as well as
      histopathological alterations induced by I/R. CONCLUSIONS: CysLT1 receptor
      antagonist montelukast reversed I/R-induced oxidant responses, improved
      microscopic damage and renal function. It seems likely that montelukast protects
      kidney tissue by inhibiting neutrophil infiltration, balancing oxidant
      antioxidant status, and regulating the generation of inflammatory mediators.

PMID- 16584890
TI  - High yield expression and purification of isotopically labelled human endothelin
      1 for use in NMR studies.
AB  - Human endothelin-1 (ET-1) is a potent vasocontractile 21-residue peptide hormone
      with significant pharmacological importance. An efficient and straightforward
      expression strategy that enables cost-effective incorporation of stable isotopes
      is not available thus far. In this report, we describe a cost-effective
      expression system in Escherichia coli for the production of ET-1 enriched with
      (15)N and (13)C isotopes. Employing thioredoxin as carrier protein, specific and
      nearly quantitative cleavage of ET-1 from the fusion was mediated by Factor Xa,
      and purification to homogeneity (final purity of >95%) was achieved by RP-HPLC.
      Purified recombinant ET-1 was found to be indistinguishable from the synthetic
      counterpart as determined by mass spectrometry and NMR spectroscopy. Our
      expression strategy offers the potential for production of isotopically labeled
      ET-1 in large (mg) quantities for the purpose of heteronuclear NMR experiments.
      Moreover, the method devised should be applicable for recombinant expression of
      small peptides in general.

PMID- 16584889
TI  - Expression, purification, and refolding of a novel immunotoxin containing
      humanized single-chain fragment variable antibody against CTLA4 and the N
      terminal fragment of human perforin.
AB  - Immunotoxins might be potential in treatment of cancer for their ability to kill
      selected cell populations. We constructed a novel immunotoxin hS83P34 by fusing N
      terminal 34 amino acid fragment of human perforin to the C-terminus of humanized
      single-chain fragment variable antibody against CTLA4. The fusion protein was
      inductively expressed as inclusion bodies at a high level about 30% of total
      bacterial proteins. After washing with buffer containing 2 M urea, the purity of
      inclusion body was about 71%. The washed inclusion bodies were solubilized in 8 M
      urea and further purified to homogeneity (approximately 92% purity) by cation
      exchange chromatography and Ni-agarose affinity chromatography under denaturing
      condition. The inclusion body refolding conditions were optimized following Pro
      Matrix Protein Refolding Guide. After refolded in Tris buffer (pH 8.0) containing
      1M urea, 0.8 M l-arginine, and 2 mM GSH:0.2 mM GSSG or 2 mM GSH:0.4 mM GSSG for
      18h at 4 degrees C, over 90% proteins were recovered from inclusion bodies. In
      vitro dose-dependent cytotoxicity assay demonstrates that hS83P34 is only toxic
      to CTLA4-positive cells. IC(50) of hS83P34 for leukemic cells Raji and 6T-CEM are
      about 0.85 and 1.3 microM individually. Whereas, CTLA4-negative endothelial cell
      ECV-304 is resistant to hS83P34.

PMID- 16584891
TI  - Characterization of a new AAA+ protein from archaea.
AB  - We investigated a new archaeal member of the AAA+ protein family (ATPases
      associated with various cellular activities) which is found in all methanogenic
      archaea and the sulphate-reducer Archaeoglobus fulgidus. These proteins cluster
      to COG1223 predicted to form a subgroup of the AAA+ ATPases. The gene from A.
      fulgidus codes for a protein of 40 kDa monomeric molecular weight, which we
      overexpressed in Escherichia coli and purified to homogeneity. The protein forms
      ring-shaped complexes with a diameter of 125A as determined by electron
      microscopy. Using sedimentation equilibrium analysis we demonstrate that it
      assembles into hexamers over a wide concentration range both in presence and
      absence of ATP. As suggested by homology to other members of the AAA+ family, the
      complex binds and hydrolyzes ATP. Michaelis-Menten analysis revealed a k(cat) of
      118 min(-1) and a K(M) of 1.4 mM at 78 degrees C. This hyperthermophilic archaeal
      ATPase is stable to 86 degrees C and the ATPase activity is maximal at this
      temperature. The protein is most homologous to the AAA-domain of FtsH from
      bacteria, while the N-terminal domain shows predicted structural homology to
      members of the CDC48 family of AAA proteins. Possible roles of this new AAA+
      protein are discussed.

PMID- 16584892
TI  - Thoughts, behaviour, and brain dynamics during navigation in the real world.
AB  - How does the human brain allow us to interact with and navigate through a
      constantly changing world? Whilst controlled experiments using functional brain
      imaging can give insightful snapshots of neuronal responses to relatively
      simplified stimuli, they cannot hope to mirror the challenges faced by the brain
      in the real world. However, trying to study the brain mechanisms supporting daily
      living represents a huge challenge. By combining functional neuroimaging, an
      accurate interactive virtual simulation of a bustling central London (UK), and a
      novel means of 'reading' participants' thoughts whilst they moved around the
      city, we ascertained the online neural correlates underpinning navigation in this
      real-world context. A complex choreography of neural dynamics was revealed
      comprising focal and distributed, transient and sustained brain activity. Our
      results provide new insights into the specific roles of individual brain areas,
      in particular the hippocampus, retrosplenial, and frontal cortices, as well as
      offering clues about how functional specialisations operate within dynamic brain
      systems.

PMID- 16584895
TI  - Cognitive dysfunction in epilepsy: case reports.
AB  - Cognitive dysfunction in people with epilepsy is a frequently encountered but
      also easily overlooked problem. In this article three patients with epilepsy are
      presented with cognitive problems due to a relapse of seizures, due to continuing
      absence seizures or as a consequence of deteriorating mental functions resulting
      from frequent complex partial seizures. In the last patient the decline in mental
      functioning was also demonstrated in a disseminated activation pattern on her
      fMRI, which contrasts with the localised activity as seen in controls on fMRI.
      Suggestions how to handle these problems in daily practice are given.

PMID- 16584893
TI  - The evolutionary origins of nematodes within the order Strongylida are related to
      predilection sites within hosts.
AB  - The evolutionary relationships of the different groups of nematodes within the
      order Strongylida based on morphological data have been speculative and the
      subject of conjecture. In this paper, we present a multigene phylogenetic
      analysis, using sequence data of the 18S and 28S ribosomal RNA genes from
      representatives of all four suborders and seven superfamilies of the Strongylida,
      to test existing hypotheses proposed for the relationships of the suborders based
      on morphological data sets. The results obtained demonstrated that the
      Strongylida is a monophyletic assemblage, with only the Metastrongylina (but not
      the other suborders) forming a distinct monophyletic clade. We show that, in
      contrast to all previous hypotheses, one major lineage comprises taxa which occur
      exclusively in the pulmonary, circulatory or nervous systems of marsupial and
      eutherian mammals, whereas a second lineage comprises species occurring in the
      gastrointestinal tracts or perirenal tissues of vertebrates, or in the lungs of
      birds. The findings suggest that the predilection site of adult nematodes and
      host type reflect the evolutionary origin of the different taxonomic groups
      within the Strongylida.

PMID- 16584894
TI  - Mitochondrial and nuclear phylogenies of Cervidae (Mammalia, Ruminantia):
      Systematics, morphology, and biogeography.
AB  - The family Cervidae includes 40 species of deer distributed throughout the
      northern hemisphere, as well as in South America and Southeast Asia. Here, we
      examine the phylogeny of this family by analyzing two mitochondrial protein
      coding genes and two nuclear introns for 25 species of deer representing most of
      the taxonomic diversity of the family. Our results provide strong support for
      intergeneric relationships. To reconcile taxonomy and phylogeny, we propose a new
      classification where the family Cervidae is divided in two subfamilies and five
      tribes. The subfamily Cervinae is composed of two tribes: the tribe Cervini
      groups the genera Cervus, Axis, Dama, and Rucervus, with the Pere David's deer
      (Elaphurus davidianus) included in the genus Cervus, and the swamp deer (Cervus
      duvauceli) placed in the genus Rucervus; the tribe Muntiacini contains Muntiacus
      and Elaphodus. The subfamily Capreolinae consists of the tribes Capreolini
      (Capreolus and Hydropotes), Alceini (Alces), and Odocoileini (Rangifer + American
      genera). Deer endemic to the New World fall in two biogeographic lineages: the
      first one groups Odocoileus and Mazama americana and is distributed in North,
      Central, and South America, whereas the second one is composed of South American
      species only and includes Mazama gouazoubira. This implies that the genus Mazama
      is not a valid taxon. Molecular dating suggests that the family originated and
      radiated in central Asia during the Late Miocene, and that Odocoileini dispersed
      to North America during the Miocene/Pliocene boundary, and underwent an adaptive
      radiation in South America after their Pliocene dispersal across the Isthmus of
      Panama. Our phylogenetic inferences show that the evolution of secondary sexual
      characters (antlers, tusk-like upper canines, and body size) has been strongly
      influenced by changes in habitat and behaviour.

PMID- 16584896
TI  - Link protein can retard the degradation of hyaluronan in proteoglycan aggregates.
AB  - OBJECTIVE: Loss of articular cartilage and intervertebral disc function in
      arthritis or disc degeneration is associated with degradation of the proteoglycan
      (PG) aggregates by either proteolysis of aggrecan or hyaluronan (HA) degradation.
      The aim of this work was to determine whether degradation of HA in PG aggregate
      degradation is influenced by link protein (LP) stabilization of the PG
      aggregates. METHODS: Aggrecan and LP were prepared from fetal bovine epiphyseal
      cartilage, and PG aggregates were formed in the presence or absence of LP. The PG
      aggregates were exposed to hyaluronidase or free radicals to promote HA
      degradation. Degradation of HA, aggrecan and LP were assessed by gel filtration
      chromatography and polyacrylamide gel electrophoresis. RESULTS: High
      concentrations of hyaluronidase cleaved both PG aggregates between each aggrecan
      molecule, whereas low concentrations gave much less cleavage of the LP-stabilized
      aggregate. High free radical concentrations gave extensive cleavage of all
      components of both PG aggregates, whereas low concentrations are more selective
      for HA damage and to a much lesser extent in the LP-stabilized aggregates. Thus
      the presence of LP caused a diminution in the capacity of both catabolic agents
      to degrade HA as long as levels of the degradative agents were not excessive.
      CONCLUSION: In addition to stabilizing the PG aggregates towards dissociation, LP
      may also help protect the PG aggregates from degradation under conditions where
      tissue catabolism is promoted.

PMID- 16584898
TI  - Percutaneous repair of aortic aneurysms: a prospective study of suture-mediated
      closure devices.
AB  - PURPOSE: To evaluate prospectively the safety and efficacy of totally
      percutaneous placement of abdominal and thoracic aortic endografts using the
      Prostar XL suture-mediated closure system. METHODS: From January 2002 to January
      2005, we attempted to insert percutaneously all bifurcated abdominal aortic and
      thoracic endografts. Consecutive patients (25 men, four women), with mean age
      74.9 years (range 44-84), underwent endovascular repair for 20 abdominal aortic
      aneurysms (AAA) and nine thoracic aortic aneurysms (repeat operation in one
      case). Endografts used included 21 Zenith (Cook), eight Talent (Medtronic), one
      AneuRx (Medtronic). For the <<pre-close>> technique, two Prostar XL 8F were used
      to close 22-24F access sites and one Prostar XL 10F to close 16F access sites.
      RESULTS: Procedural success was achieved in 21/29 (72.4%) patients and in 39/47
      access sites (83%). Closure of 22-24F access sites with tandem 8F Prostar devices
      was successful in 23/29 (79.3%) cases. Closure of 16F access sites with 10F
      Prostar device was successful in 16/18 (88.8%) cases. There were seven peri
      procedural failures requiring surgery to repair the femoral artery in three
      cases. Four access complications healed without intervention. Overall 25/29
      (86.2%) patients had complete percutaneous repair. No late complications were
      detected during follow-up (median 17.5 months). CONCLUSIONS: Percutaneous
      treatment of patients with AAA and thoracic aneurysms is feasible in most cases,
      with a very low risk of access-related complication, providing that the operator
      has sufficient practical experience of this technique.

PMID- 16584897
TI  - Proliferating effects of the flavonoids daidzein and quercetin on cultured
      chicken primordial germ cells through antioxidant action.
AB  - Primordial germ cells (PGCs) are undifferentiated pluripotent stem cells, whose
      proliferation is influenced by many internal and external factors. In the present
      study, a PGC-somatic cell co-culture model was established to evaluate effects of
      the flavonoids daidzein (DAI) and quercetin (QUE) on proliferation of PGCs from
      embryonic chickens. PGCs were isolated from the germinal ridge of 3.5-4day
      embryos and cultured in 5% fetal calf serum (FCS)-supplemented Medium 199. PGC
      subculture was carried out on chicken embryonic fibroblast feeder (CEF) or
      follicular granulosa cell feeder (GCF) layers. The subcultured PGCs were
      challenged with flavonoids alone or in combination with a reactive oxygen
      substance (ROS)-producing system on CEF for 48h. The results showed a better
      supporting effect of CEF than GCF. Flavonoids (1microg/ml) significantly promoted
      PGC proliferation, which could be markedly inhibited by ROS. The oxidative damage
      by ROS was further manifest by decreased superoxide dismutase activity and
      glutathione levels. In addition, activation of protein kinase A (PKA) by
      forskolin significantly stimulated PGC proliferation, but PKA inhibitor H89
      inhibited the proliferating effects induced by DAI and QUE. These results
      indicated that cultured PGCs respond to exogenous agents on proliferation and
      that antioxidant flavonoids could restore the intracellular antioxidant system
      and promote PGC proliferation via their antioxidant action involving the PKA
      signaling pathway.

PMID- 16584900
TI  - Influence of presentation on outcome in abdominal aortic aneurysm repair.
AB  - OBJECTIVES: In the absence of formal screening abdominal aortic aneurysms (AAA)
      are detected in an opportunistic manner. Many remain asymptomatic and undetected
      until they rupture. Incidentally discovered small AAAs are entered into a
      surveillance programme until they reach a suitable size for repair. The aim of
      this study was to examine trends in the management of AAA and whether the method
      of presentation had an effect on subsequent mortality. DESIGN: Observational
      study in UK district general hospital. MATERIALS/METHODS: This study reports a
      single surgeon case series identified using a prospectively maintained database.
      Data on mode of presentation, management and mortality were retrieved from case
      notes, PIMS hospital database and the Office of National Statistics. RESULTS: Two
      hundred and five patients were referred with AAAs between 1992 and 2004, 78%
      presenting in elective circumstances. The surveillance programme fed 33% of the
      operated cases. Two aneurysms ruptured whilst under surveillance. Overall
      elective operative mortality was 11.8% and has progressively decreased over time.
      Thirty-day operated mortality was significantly lower in patients having a period
      of surveillance than those having immediate elective repair (2.3 vs. 16.3%,
      p=0.018). A slight reduction in emergency AAA repairs was noted over the study
      period (r2=0.6) although registered aneurysm deaths continue to increase
      (r2=0.83). CONCLUSIONS: Elective mortality following AAA surgery decreased over
      the study period. Outcome was better in those patients who had surgery for
      aneurysms that had been under surveillance. Despite opportunistic screening the
      population adjusted mortality rate of aortic aneurysms showed a progressive
      increase. A reduction in deaths from aneurysms is unlikely without a formal
      screening programme.

PMID- 16584901
TI  - Re: Mehta T, Venkata Subramaniam A, Chetter I, McCollum P. Assessing the validity
      and responsiveness of disease-specific quality of life instruments in
      intermittent claudication. Eur J Vasc Endovasc Surg 2006;31:46-52.

PMID- 16584902
TI  - A novel R416C mutation in human DMT1 (SLC11A2) displays pleiotropic effects on
      function and causes microcytic anemia and hepatic iron overload.
AB  - A patient suffering from microcytic anemia and hepatic iron overload was found to
      be compound heterozygote for polymorphisms in the iron transporter DMT1 (Nramp2,
      SLC11A2), including a 3-bp deletion (DMT1(delCTT)) in intron 4 that partially
      impairs splicing and an amino acid substitution (DMT1(C1246T), R416C) at a
      conserved residue in transmembrane domain 9 of the protein. The functional
      properties and possible contribution to disease of the DMT1 R416C mutation were
      studied in independent mutants at that position (R416C, R416A, R416K, R416E)
      expressed in LLC-PK(1) kidney cells. Non-conservative substitutions at R416 (C,
      A, E) cause multiple functional deficiencies including defective protein
      processing, loss of transport activity, impaired cell surface targeting, and
      recycling through endosomes, concomitant with retention of the transporter in the
      endoplasmic reticulum. Conversely, a conservative isoelectric substitution
      (R416K) was less vulnerable, resulting in a functional transporter that was
      properly processed and targeted to the cell surface and to recycling endosomes.
      We propose that DMT1(C1246T) (R416C) represents a complete loss-of-function, and
      that a quantitative reduction in DMT1 expression is the cause of the microcytic
      anemia and iron overload in the patient.

PMID- 16584903
TI  - Signal transduction pathways leading to Ca2+ release in a vertebrate model
      system: lessons from Xenopus eggs.
AB  - At fertilization, eggs unite with sperm to initiate developmental programs that
      give rise to development of the embryo. Defining the molecular mechanism of this
      fundamental process at the beginning of life has been a key question in cell and
      developmental biology. In this review, we examine sperm-induced signal
      transduction events that lead to release of intracellular Ca(2+), a pivotal
      trigger of developmental activation, during fertilization in Xenopus laevis.
      Recent data demonstrate that metabolism of inositol 1,4,5-trisphosphate (IP(3)),
      a second messenger for Ca(2+) release, is carefully regulated and involves
      phospholipase C (PLC) and the tyrosine kinase Src. Roles of other potential
      regulators in this pathway, such as phosphatidylinositol 3-kinase, heterotrimeric
      GTP-binding protein, phospholipase D (PLD) and phosphatidic acid (PA) are also
      discussed. Finally, we address roles of egg lipid/membrane microdomains or
      'rafts' as a platform for the sperm-egg membrane interaction and subsequent
      signaling events of egg activation.

PMID- 16584904
TI  - Characterisation of the pig acute phase protein response to road transport.
AB  - The acute phase protein (APP) response was evaluated after prolonged
      transportation of pigs under commercial conditions. Elevated serum APP
      concentrations were observed in two groups of boars immediately after their
      arrival at a destination farm compared with within-animal control samples
      obtained one month later. The effect was more pronounced in the first group of
      pigs conveyed under average transport conditions (Transport 1, 24 h), although
      the second group was transported for a longer time period (Transport 2, 48 h) but
      in superior transport conditions. In a second trial, pigs were sampled before
      transport, on arrival at an abattoir (following 12 h transport), and at the
      slaughter-line (after 6 h lairage). Significant increases in major acute phase
      protein (Pig-MAP), haptoglobin, serum amyloid A, C-reactive protein, and a
      decrease in apolipoprotein A-I, were observed at slaughter. The results
      demonstrate that shipment of pigs by road can result in an APP response that is
      probably related to the stress of transport.

PMID- 16584905
TI  - A critical appraisal of methods used in early clinical development of novel drugs
      for the treatment of asthma.
AB  - Asthma is a heterogeneous disorder characterized by chronic airway inflammation,
      hyperresponsiveness and remodeling. Being the hallmark of asthma, airway
      inflammation has become the most important target for therapeutic agents.
      Consequently, during the past decade various semi-and non-invasive methods have
      been explored to sample the airway inflammation in asthma. In this review, we
      provide a practical overview of the current status of various sampling techniques
      including sputum induction, exhaled breath analysis, and bronchoprovocation tests
      (BPTs). We focus on their applicability for monitoring in clinical practice and
      in intervention trials in asthma.

PMID- 16584907
TI  - Linking social capital and self-rated health: a multilevel analysis of 11,175 men
      and women in Sweden.
AB  - This multilevel study included 11,175 participants interviewed 2000-2002 in
      Sweden. The association between neighbourhood linking social capital (voting in
      national elections) and self-rated health was analysed. Individuals living in
      neighbourhoods with the lowest levels of linking social capital exhibited a
      significantly higher risk of poor health than individuals living in
      neighbourhoods with the highest levels of linking social capital, after
      adjustment for individual characteristics, including individual voting. The
      neighbourhood variance indicated significant differences in self-rated health
      between neighbourhoods. Both individuals and neighbourhoods need to be targeted
      in order to enhance people's health in neighbourhoods with low linking social
      capital.

PMID- 16584906
TI  - Hydrophobic cluster analysis and modeling of the human Rh protein three
      dimensional structures.
AB  - Rh (Rhesus) is a major blood group system in man, which is clinically significant
      in transfusion medicine. Rh antigens are carried by an oligomer of two major
      erythroid specific polypeptides, the Rh (D and CcEe) proteins and the RhAG
      glycoprotein, that shared a common predicted structure with 12 transmembrane a
      helices (M0 to M11). Non erythroid homologues of these proteins have been
      identified (RhBG and RhCG), notably in diverse organs specialized in ammonia
      production and excretion, such as kidney, liver and intestine. Phylogenetic
      studies and experimental evidence have shown that these proteins belong to the
      Amt/Mep/Rh protein superfamily of ammonium/methylammonium permease, but another
      view suggests that Rh proteins might function as CO2 gas channels. Until recently
      no information on the structure of these proteins were available. However, in the
      last two years, new insight has been gained into the structural features of Rh
      proteins (through the determination of the crystal structures of bacterial AmtB
      and archeaebacterial Amt-1. Here, models of the subunit and oligomeric
      architecture of human Rh proteins are proposed, based on a refined alignment with
      and crystal structure of the bacterial ammonia transporter AmtB, a member of the
      Amt/Mep/Rh superfamily. This alignment was performed considering invariant
      structural features, which were revealed through Hydrophobic Cluster Analysis,
      and led to propose alternative predictions for the less conserved regions,
      particularly in the N-terminal sequences. The Rh models, on which an additional
      Rh-specific, N-terminal helix M0 was tentatively positioned, were further
      assessed through the consideration of biochemical and immunochemical data, as
      well as of stereochemical and topological constraints. These models highlighted
      some Rh specific features that have not yet been reported. Among these, are the
      prediction of some critical residues, which may play a role in the channel
      function, but also in the stability of the subunit structure and oligomeric
      assembly. These results provide a basis to further understand the
      structure/function relationships of Rh proteins, and the alterations occurring in
      variant phenotypes.

PMID- 16584908
TI  - Formation of a nuclear complex containing the p53 tumor suppressor, YB-1, and the
      Werner syndrome gene product in cells treated with UV light.
AB  - YB-1 is a multifunctional protein involved in the regulation of transcription,
      translation, and mRNA splicing. In recent years, several laboratories have
      demonstrated that YB-1 is also directly involved in the cellular response to
      genotoxic stress. Accordingly, one report has indicated that the Werner syndrome
      gene product (WRN) is eluted from an YB-1 affinity chromatography column. Werner
      syndrome is a rare disorder characterized by the premature onset of a number of
      age-related diseases, including cancer. The gene responsible for Werner syndrome
      encodes a DNA helicase/exonuclease protein believed to be involved in some aspect
      of DNA repair with p53. In this study, we demonstrate that the tumor suppressor,
      p53, bridges the WRN and YB-1 proteins in vitro. Microscopic analyses of
      fluorescent-tagged proteins and co-immunoprecipitation experiments confirmed the
      formation of an YB-1/p53/WRN complex in human cells, but only after treatment
      with UV light. We also confirmed that p53 is a major player in the translocation
      of GFP-YB-1 fusion proteins from the cytoplasm to several nuclear foci containing
      WRN proteins upon UV irradiation. Such translocation did not occur in cells
      treated with the topoisomerase inhibitor, etoposide, or the radiomimetic drug,
      bleomycin. Such results suggest that an YB-1/p53/WRN complex is formed in
      response to the emergence of specific DNA lesions in cells.

PMID- 16584910
TI  - Zap! Magnetic tricks on conscious and unconscious vision.
AB  - Blindsight, the remarkable capability to react to unseen visual stimuli, has thus
      far only been demonstrated in patients and monkeys with a lesion to primary
      visual cortex. A recent study by Boyer, Harrison and Ro demonstrates blindsight
      in normal human observers, using TMS to block visual processing. Combined with
      other work, this opens new vistas towards understanding mechanisms of conscious
      and unconscious vision.

PMID- 16584909
TI  - Bootstrapping conceptual deduction using physical connection: rethinking frontal
      cortex.
AB  - The age at which infants can demonstrate the ability to deduce abstract rules can
      be reduced by more than half, from 21 months to 9 months. The key is to introduce
      a physical connection between the items to be conceptually related. I argue here
      that making the same change in how items are presented might also help some
      preschoolers with learning delays, especially some children with autism. I also
      suggest that the roles of premotor and ventrolateral prefrontal cortices in
      deducing abstract rules might have been misinterpreted behaviorally and
      anatomically. The crucial brain region may be the periarcuate, which partially
      overlaps both premotor and lateral prefrontal cortex. The cognitive ability made
      possible by this region might be something far more elementary than previously
      considered: the ability to perceive conceptual connections in the absence of
      physical connection.

PMID- 16584911
TI  - Genotoxic risk assessment of pathology and anatomy laboratory workers exposed to
      formaldehyde by use of personal air sampling and analysis of DNA damage in
      peripheral lymphocytes.
AB  - A study was conducted to evaluate the genotoxic effect of occupational exposure
      to formaldehyde on pathology and anatomy laboratory workers. The level of
      exposure to formaldehyde was determined by use of passive air-monitoring badges
      clipped near the breathing zone of 59 workers for a total sampling time of 15 min
      or 8 h. To estimate DNA damage, a chemiluminescence microplate assay was
      performed on 57 workers before and after a 1-day exposure. Assessment of
      chromosomal damage was carried out by use of the cytokinesis-blocked micronucleus
      assay (CBMN) in peripheral lymphocytes of 59 exposed subjects in comparison with
      37 controls matched for gender, age, and smoking habits. The CBMN assay was
      combined with fluorescent in situ hybridization with a pan-centromeric DNA probe
      in 18 exposed subjects and 18 control subjects randomized from the initial
      populations. Mean concentrations of formaldehyde were 2.0 (range <0.1-20.4 ppm)
      and 0.1 ppm (range <0.1-0.7 ppm) for the sampling times of 15 min and 8 h,
      respectively. No increase in DNA damage was detected in lymphocytes after a one
      workday exposure. However, the frequency of binucleated micronucleated cells was
      significantly higher in pathologists/anatomists than in controls (16.90/00+/-9.3
      versus 11.10/00+/-6.0, P=0.001). The frequency of centromeric micronuclei was
      higher in exposed subjects than in controls (17.30/00+/-11.5 versus 10.30/00+/
      7.1) but the difference was not significant. The frequency of monocentromeric
      micronuclei was significantly higher in exposed subjects than in controls
      (11.00/00+/-6.2 versus 3.10/00+/-2.4, P<0.001), while that of the acentromeric
      micronuclei was similar in exposed subjects and controls (3.70/00+/-4.2 and
      4.10/00+/-2.7, respectively). The enhanced chromosomal damage (particularly
      chromosome loss) in peripheral lymphocytes of pathologists/anatomists emphasizes
      the need to develop safety programs.

PMID- 16584912
TI  - Relationship between p53 status and 5-fluorouracil sensitivity in 3 cell lines.
AB  - Mouse lymphoma L5178Ytk+/- (MOLY) cells and human lymphoblastoid TK6 and WTK-1
      cells are widely used to detect mutagens in vitro. MOLY and WTK-1 cells have a
      p53 mutation, while TK6 cells, which were derived from the same parental line as
      WTK-1 cells, do not. In this study, we tested the clastogen 5-fluorouracil (5-FU)
      in the Tk assay and the in vitro micronucleus (MN) assay in MOLY, TK6, and WTK-1
      cells to clarify whether differential responses were related to p53 gene status.
      We also determined the effect of 5-FU on the frequency of apoptotic cells and on
      cell cycle distribution in each cell line. Furthermore, we measured the activity
      of the 5-FU metabolizing enzymes (thymidylate synthetase (TS), dihydrouracil
      dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), and thymidine
      phosphorylase (TP)) in each cell line. We treated MOLY cells with 1.0-8.0
      microg/mL 5-FU for 3 h and TK6 and WTK-1 cells with 1.56-25 and 3.13-50
      microg/mL, respectively, for 4 h. In MOLY cells, the mutation frequency (MF) and
      MN frequency increased. In WTK-1 cells, the MN frequency but not the MF
      increased. In TK6 cells, neither the MF nor the MN frequency increased.
      Furthermore, the IC50 of 5-FU was lower in MOLY cells than in the human cells.
      The response to 5-FU treatment differed in other ways as well. At the same level
      of cytotoxicity, the frequency of apoptotic cell was highest in TK6 cells. The
      cell cycle was delayed just after treatment in MOLY cells while the delay
      appeared 24 h later in TK6 and WTK-1 cells. Nothing in our analysis, however,
      revealed marked differences between the cell lines that could account for the
      severe cytotoxic and mutagenic responses that 5-FU elicited only in MOLY cells. 5
      FU is phosphorylated by OPRT and TP and detoxified by DPD. MOLY cells have higher
      OPRT activity and markedly lower DPD and TP activity than TK6 and WTK-1 cells.
      The content of TS, however, the target enzyme of 5-FU, was similar in all cell
      lines, suggesting that 5-FU was more readily phosphorylated and less readily
      detoxified in MOLY cells than in TK6 and WTK-1 cells. MOLY cells were more
      sensitive to 5-FU than WTK-1 cells even though both have a mutated p53 gene,
      suggesting that the different responses to 5-FU were due to differences in 5-FU
      metabolism rather than the p53 status.

PMID- 16584913
TI  - A new cercaria and metacercaria of Acanthoparyphium (Echinostomatidae) found in
      an intertidal snail Zeacumantus subcarinatus (Batillaridae) from New Zealand.
AB  - A new 23-collar-spined cercaria and metacercaria are described from intertidal
      molluscs of the coast of New Zealand. The new cercaria found emerging from the
      mud snails Zeacumantus subcarinatus (Sowerby) (Prosobranchia: Batillariidae) is
      characterized mainly by the number and arrangement of the cephalic glands, the
      size of the suckers, and the size and number of the collar spines. The cercaria
      encysts in the cockle Austrovenus stutchburyi (Wood) (Bivalvia: Veneridae) which
      lives in sympatry with the first intermediate host throughout New Zealand.
      Laboratory infections of cockles by cercariae from naturally infected snails
      resulted in metacercariae identical to those found in naturally infected cockles.
      The main features of the cercaria and metacercaria are the presence of a reniform
      collar with 23 spines, two pairs of small cephalic glands at the oral sucker
      level, another two pairs of much longer ones posterior to the pharynx, and the
      excretory vesicle Y-shaped with the main collecting canals extending to the
      anterior level of the ventral sucker. Each of the main collecting canals had 10
      11 pairs of bilateral diverticula between the anterior edge of the ventral sucker
      and anterior body end. A brief discussion of its possible life cycle and ecology
      is also provided.

PMID- 16584914
TI  - 2-Mercaptoethane sulfonate (MESNA) protects against biliary obstruction-induced
      oxidative damage in rats.
AB  - The aim of this study was to assess the antioxidant and antifibrotic effects of
      chronic administration of 2-mercaptoethane sulfonate (MESNA) on oxidative liver
      damage and fibrosis induced by biliary obstruction in rats. Liver fibrosis was
      induced in male Wistar albino rats by bile duct ligation and scission (BDL).
      MESNA (150mg/kg, i.p.) or saline was administered for 28 days. At the end of the
      experiment, rats were killed by decapitation. Serum aspartate aminotransferase
      (AST), and alanine aminotransferase (ALT) levels were determined to assess liver
      function. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehidrogenase (LDH)
      were also assayed in serum samples. Liver tissues were taken for determination of
      the free radicals, hepatic malondialdehyde (MDA) levels, an end product of lipid
      peroxidation; glutathione (GSH) levels, a key antioxidant; myeloperoxidase (MPO)
      activity, as an indirect index of neutrophil infiltration. Hepatic collagen
      content, as a fibrosis marker was also determined. Serum AST, ALT, LDH and TNF
      alpha levels were elevated in the BDL group as compared to control group, while
      this increase was significantly decreased by MESNA treatment. BDL caused a
      significant (p<0.05-0.001) decrease in GSH levels while MDA levels and MPO
      activity were increased in the liver tissue. These changes were reversed by MESNA
      treatment. Collagen contents of the liver tissue was increased by BDL (p<0.001),
      and reversed back to the control levels with MESNA. Since MESNA administration
      alleviated the BDL-induced oxidative injury of the liver and improved the hepatic
      functions, it seems likely that MESNA with its antioxidant and antifibrotic
      properties, may be of potential therapeutic value in protecting the liver
      fibrosis and oxidative injury due to biliary obstruction.

PMID- 16584915
TI  - A comparison of subdermal wire electrodes with collodion-applied disk electrodes
      in long-term EEG recordings in ICU.
AB  - OBJECTIVE: To compare long-term electroencephalographic (EEG) recordings of
      standard collodion-applied scalp disk electrodes (SDEs) with newly developed
      subdermal wire electrodes (SWEs) in comatose intensive care unit (ICU) patients.
      METHODS: Ten comatose ICU patients had simultaneous recordings from 8 active SDEs
      and 8 active SWE for >24 h. The timing and number of 60 Hz and other electrode
      artifacts were compared for each set of electrodes by an EEGer who read the
      recordings in a blinded manner. RESULTS: Sixty Hertz artifact was seen in 16 of
      80 SDE and one of 80 SWEs within the first 6 h (P=0.0002). Large, persistent
      artifacts occurred in 30/80 SDE and 8 of 80 SWE (P=0.0001). Motion artifact with
      chest physiotherapy was more common in SWEs. CONCLUSIONS: SWE are less
      susceptible to artifacts and are more suitable for the long-term EEG monitoring
      in ICU. SIGNIFICANCE: This is the first controlled study that demonstrates the
      superiority of SWEs compared to SDEs in an ICU population.

PMID- 16584916
TI  - Activity of lysosomal exoglycosidases in the serum of patients with chronic Lyme
      arthritis.
AB  - To examine the role of lysosomal exoglycosidases in the pathogenesis of Lyme
      arthritis we studied a group of 18 patients aged 18-72 (mean: 46 yr) diagnosed
      with chronic arthritis in the course of borreliosis. The control group was
      composed of 20 healthy volunteers (health service employees) aged 25-65 (mean: 45
      yr) with no detectable serum anti-Borrelia burgdorferi antibodies. We found that
      N-acetyl-beta-d-hexosaminidase (HEX) was significantly increased and beta
      galactosidase and alpha-mannosidase also showed an increase in Lyme arthritis
      patients compared to healthy persons and normalised after treatment with
      doxycycline. Our results suggest that HEX is a sensitive enzymatic marker of Lyme
      arthritis and it may be used to monitor the course of the disease and the
      efficiency of treatment.

PMID- 16584917
TI  - Factors associated with chronic plantar heel pain: a systematic review.
AB  - Chronic plantar heel pain (CPHP) is one of the most common soft tissue disorders
      of the foot, yet its aetiology is poorly understood. The purpose of this
      systematic review was to examine the association between CPHP and the various
      aetiological factors reported in the literature. Seven electronic databases and
      the reference lists of key articles were searched in August 2005. The resulting
      list of articles was assessed by two independent reviewers according to pre
      determined selection criteria and a final list of articles for review was
      created. The methodological quality of the included articles was assessed and the
      evidence presented in each of the articles was descriptively analysed. From the
      16 included articles, body mass index in a non-athletic population and the
      presence of calcaneal spur were the two factors found to have an association with
      CPHP. Increased weight in a non athletic population, increased age, decreased
      ankle dorsiflexion, decreased first metatarsophalangeal joint extension and
      prolonged standing all demonstrated some evidence of an association with CPHP.
      Evidence for static foot posture and dynamic foot motion was inconclusive and
      height, weight and BMI in an athletic population were not associated with CPHP.
      The findings of this review should be used to guide the focus of prospective
      cohort studies, the results of which would ultimately provide a list of risk
      factors for CPHP. Such a list is essential in the development of new and improved
      preventative and treatment strategies for CPHP.

PMID- 16584918
TI  - Incidence of injuries in the New Zealand national rugby league sevens tournament.
AB  - This study investigated the incidence, site, nature and causes of injuries
      sustained in the New Zealand national rugby league sevens tournament. A total of
      218 players competing in 47 matches were studied. All injuries sustained within
      the tournament were prospectively recorded. Injuries were categorised according
      to the severity assessment at the time of the injury. Information obtained
      included the time, site, nature and cause of the injury. The incidence of injury
      was 497.6 per 1000 playing hours. More than 40% (216.1 per 1000) of injuries
      sustained occurred within the lower limbs. The shoulder was the single most
      commonly injured site (78.6 per 1000). Sprains were the most common injury type
      (189.9 per 1000). The ball-carrier sustained significantly more (p<0.05) injuries
      than the tackling player (216.1 per 1000 [43.4%] versus 117.8 per 1000 [23.7%]).
      There were significantly more injuries on the first day of competition than on
      the second day of competition (600.4 per 1000 [76.3%] versus 320.9 per 1000
      [23.7%]). The findings of higher injury rates on the first day of competition and
      during the second period of matches suggest that playing intensity and player
      fatigue may contribute to injuries in rugby league sevens.

PMID- 16584919
TI  - Adenosine signalling in airways.
AB  - Current research endeavours indicate that adenosine elicits strong inflammatory
      responses in the lung and might be involved in the pathogenic mechanisms of
      chronic inflammatory disorders of the airways such as asthma and chronic
      obstructive pulmonary disease (COPD). The contribution of adenosine-associated
      effector mechanisms to the initiation, persistence and progression of the
      inflammatory response is highly heterogeneous and is dictated by the expression
      pattern of four different adenosine receptors. Selective activation or blockade
      of these sites can therefore be exploited in an attempt to generate novel
      therapies for asthma and COPD. In addition, an important development is the use
      of adenosine (or AMP) as a diagnostic test for discriminating asthma from COPD,
      and as an accurate biomarker to monitor corticosteroid requirements in asthma. It
      is likely that therapies interfering with adenosine signalling in the airways
      will offer a considerable advance in the management of asthma and COPD.

PMID- 16584920
TI  - SLAM family receptors and SAP-related adaptors: matters arising.
AB  - The signaling lymphocytic activation molecule (SLAM) and SLAM-associated protein
      (SAP) families have key roles in normal immunity. They have also been implicated
      in diseases such as immunodeficiencies and auto-immunity. However, recent
      findings raise issues requiring examination in future investigations of these
      molecules. First, Slam-related genes have peculiar features that need to be
      considered when generating mice lacking SLAM family receptors. Second, there are
      outstanding questions concerning the functions and mechanisms of action of the
      SLAM and SAP families. Among these is the possibility that certain properties of
      these families are not conserved between humans and mice, a controversy about the
      role of SAP in B cells, gaps in our understanding of the mechanisms by which SAP
      and Ewing's sarcoma-related transcript (EAT)-2 mediate their signals, and the
      notion that SLAM family receptors might regulate components of normal immunity in
      the absence of SAP-related adaptors. We address these issues and discuss the
      recent progress in this research area.

PMID- 16584921
TI  - Apoptotic cell removal in development and tissue homeostasis.
AB  - Cell deletion is a physiological process for the development and maintenance of
      tissue homeostasis in metazoa. This is mainly achieved by the induction of
      various forms of programmed cell death followed by the recognition and removal of
      the targeted cells by phagocytes. In this review, we will discuss cell deletion
      in relation to the development and function of the innate immune system,
      particularly of the mononuclear phagocyte system (MPS), its ontogeny and
      potential role in tissue remodeling in the embryo and adult. Ongoing studies are
      addressing the roles of professional phagocytes of the MPS and neighboring tissue
      cells in dying cell removal, and candidate molecules that might attract
      mononuclear phagocytes to the dying cells. The potential phagocyte must
      discriminate between living and dying cells; current concepts for this
      discrimination derive from the observation of newly exposed ligands on the dying
      cells and new evidence for direct inhibition of uptake by viable cells.

PMID- 16584922
TI  - Waking up T cells to counteract chronic infections.
AB  - Memory T-cell responses generated in chronic viral infections can show functional
      defects contributing to poor viral control. Recently, signaling through the PD-1
      receptor on CD8+ T cells was shown to cause cells to express an exhausted
      phenotype in an animal model of chronic infection. By blocking the interaction of
      PD-1 with its ligand PD-L1, virus-specific CD8+ T cells exhibited expansion and
      improved infection control. This approach could prove valuable to manage chronic
      infections.

PMID- 16584923
TI  - The role of antibody-mediated immunity in defense against Mycobacterium
      tuberculosis: advances toward a novel vaccine strategy.
AB  - Antibody-mediated immunity has been historically considered to have no role in
      host-defense against Mycobacterium tuberculosis. In recent years, studies from
      our group as well as others have challenged this traditional thinking. Using
      monoclonal antibodies, researchers demonstrated that antibodies can modify
      various aspects of mycobacterial infection to the benefit of the host. A review
      of recent experimental evidence in support of a role for antibodies in host
      defense against mycobacterial infections is presented. Challenges to the field
      and an outline of future directions with particular attention to research leading
      to the development of a novel vaccine strategy, are emphasized.

PMID- 16584925
TI  - NAD(P)H oxidase-induced oxidative stress in sympathetic ganglia of apolipoprotein
      E deficient mice.
AB  - Superoxide anion (O2*-) is increased throughout the arterial wall in
      atherosclerosis. The oxidative stress contributes to lesion formation and
      vascular dysfunction. In the present study, we tested the hypothesis that NAD(P)H
      oxidase-derived O2*- is increased in nodose sensory ganglia and sympathetic
      ganglia of apolipoprotein E deficient (apoE-/-) mice, an established animal model
      of atherosclerosis. O2*- measured ex vivo by L-012-enhanced chemiluminescence was
      increased by 79+/-17% in whole sympathetic ganglia from apoE-/- mice (n=5)
      compared with sympathetic ganglia from control mice (n=5) (P<0.05). In contrast,
      O2*- was not elevated in nodose ganglia from apoE-/- mice. Dihydroethidium
      staining confirmed the selective increase in O2*- in sympathetic ganglia of apoE
      /- mice, and revealed the contribution of both neurons and non-neuronal cells to
      the O2*- generation. We investigated the enzymatic source of increased O2*- in
      sympathetic ganglia of apoE-/- mice. The mRNA expression of gp91phox, p22phox,
      p67phox, and p47phox subunits of NAD(P)H oxidase measured by real time RT-PCR was
      increased approximately 3-4 fold in sympathetic ganglia of apoE-/- mice (n=5)
      compared with control ganglia (n=5). NADPH oxidase activity measured by lucigenin
      chemiluminescence was increased by 68+/-12% in homogenates of sympathetic ganglia
      from apoE-/- mice (n=7) compared with control ganglia (n=7) (P<0.05). The results
      identify sympathetic ganglia as a novel site of oxidative stress in
      atherosclerosis, and suggest that upregulation of NAD(P)H oxidase is the source
      of increased O2*- generation. We speculate that oxidative stress in sympathetic
      ganglia may contribute to impaired baroreflex control of sympathetic nerve
      activity.

PMID- 16584924
TI  - Detection of cell cycle- and differentiation stage-dependent human telomerase
      reverse transcriptase expression in single living cancer cells.
AB  - Elevated telomerase activity is an important molecular signature of cancer cells
      and primitive cells in regenerative tissues. However, isolation of single living
      cells with endogenous telomerase activity has not yet been possible. Here, we
      developed adenovirus serotype 35 tropism-based vectors encoding destabilized
      enhanced green fluorescence protein with a half-life of 2 h (d2EGFP) driven by
      the human telomerase reverse transcriptase (hTERT) promoter. As assessed in
      telomerase-positive or -negative cell lines, the d2EGFP expression positively
      correlated with hTERT transcript content and telomerase activity. In retinoic
      acid-induced differentiating HL-60 cells, the d2EGFP expression is diminished in
      the same manner as the hTERT expression. Individual cells from HeLa and HL-60
      cell lines exhibited heterogeneous d2EGFP expression, which was cell cycle
      dependent, as the sorted d2EGFP+ HL-60 cells contained twice as many cells in
      S/G2/M phase of the cell cycle compared with the d2EGFP- HL-60 cells. However,
      both cell populations exhibited the same proliferation and regeneration
      capacities. Heterogeneous d2EGFP expression was also detected in xenograft
      glioblastoma multiforme cells with tumor formation capacity. Thus, d2EGFP
      expression reported cell cycle- and differentiation stage-dependent hTERT
      expression. Our study facilitates isolation and characterization of single living
      cells with telomerase activity.

PMID- 16584926
TI  - Cross-talk between the sarcoplasmic reticulum and the mitochondrial calcium
      handling systems may play an important role in the regulation of contraction in
      anococcygeus smooth muscle.
AB  - Mitochondrial Ca(2+) and its relation with the contraction induced by
      phenylephrine was investigated. In normal Ca(2+), carbonyl cyanide p-(trifluoro
      methoxy)phenyl-hydrazone (FCCP) and oligomycin produced contraction similar to
      that promoted by phenylephrine. Phenylephrine-induced contraction was reduced by
      FCCP+oligomycin. In Ca(2+)-free, FCCP+oligomycin did not induce contraction.
      Response to FCCP+oligomycin was reduced upon Ca(2+) repletion and this response
      was lower than that to phenylephrine. Ca(2+) concentration was increased by
      FCCP+oligomycin. Since a profuse net of sarcoplasmic reticulum encloses
      mitochondria, a cross-talk between the two organelles may play an important role
      in the phenylephrine-induced contraction in presence of Ca(2+) encountered in
      both sarcoplasmic reticulum and extracellular medium of anococcygeus cells.

PMID- 16584927
TI  - Regulation of cough by secondary sensory inputs.
AB  - We have reviewed the role of afferent inputs and blood chemical changes to the
      central nervous system, and the way in which they modify the cough and expiration
      reflexes (CR and ER). Slowly adapting pulmonary stretch receptors (SARs) augment
      the CR, insofar as when their activity is abolished the CRs from the
      tracheobronchial (TB) tree and larynx are abolished or weakened. However,
      stimulation of SARs by lung inflation has an inconsistent effect on the CR.
      Activation of SARs strongly potentiates the ER from the vocal folds, by a reflex
      mechanism, and inhibition of SARs weakens the ER. Bronchopulmonary C-fibre
      receptors inhibit the CR, as do capsaicin-sensitive afferents from the heart and
      splanchnic bed, cutaneous cold receptors and those that respond to chest wall
      vibration. Nasal receptors responsive to the irritant agent capsaicin potentiate
      the reflex. Acute hypoxia also augments the CR, and the reflex is down-regulated
      by carotid body resection. On the other hand, the CR is inhibited by prolonged
      hypoxia and hyperoxia, and by hypercapnia. Thus different inputs to the cough
      controlling mechanism in the brainstem have very varied effects on the CR. We
      conclude that the sensitivities of the CR and ER can be modified in a large
      variety of physiological and clinical conditions, and that there is no clear
      relationship between the reflexes and changes in breathing caused by the
      interventions.

PMID- 16584928
TI  - Modified high-performance liquid chromatography with electrochemical detection
      method for plasma measurement of levodopa, 3-O-methyldopa, dopamine, carbidopa
      and 3,4-dihydroxyphenyl acetic acid.
AB  - Plasma measurements of levodopa and its major metabolites including dopamine and
      3-O-methyldopa have been limited by cumbersome methods and poor sensitivity
      within relatively narrow ranges of plasma levels. We now report a modification of
      an HPLC method that permits concomitant measurements of a wide range of
      concentrations of levodopa, dopamine (DA), carbidopa, 3-O-methyldopa (3-OMD) and
      3,4-dihydroxyphenyl acetic acid (DOPAC) from one HPLC injection. The recoveries
      ranged from 77 to 107% with an intra-day precision around 5% (CV) and inter-day
      CV's about 10-20%. This validated method will simplify pharmacokinetic studies of
      levodopa and its metabolites for mechanistic studies or therapeutic clinical
      monitoring which play a crucial role in development of strategies to prolong
      motor benefits from individual doses and reduce involuntary movements called
      dykinesias.

PMID- 16584929
TI  - High-performance liquid chromatographic method for the determination of
      gemcitabine and 2',2'-difluorodeoxyuridine in plasma and tissue culture media.
AB  - Gemcitabine, a pyrimidine antimetabolite undergoes metabolism by plasma and liver
      cytidine deaminase to form the inactive compound, 2',2'-difluorodeoxyuridine
      (dFdU). The parent molecule is activated by intracellular phosphorylation. To
      evaluate the population pharmacokinetics in patients receiving gemcitabine, and
      to test the relation between gemcitabine infusion rate and antitumor activity in
      an in vitro bioreactor cell culture system, we developed and validated a
      sensitive and specific HPLC-UV method for gemcitabine and dFdU. Deproteinized
      plasma is vortexed, centrifuged, and 25 microL of the acidified extract sample is
      injected onto a Waters Spherisorb 4.6 mm x 250 mm, 5 microm C18 column at 40
      degrees C. The mobile phase (flow rate, 1.0 mL/min) consists of 10:90 (v/v)
      acetonitrile-aqueous buffer (50 mM sodium phosphate and 3.0 mM octyl sulfonic
      acid, pH 2.9). Gemcitabine, dFdU, and the internal standard, 2'-deoxycytidine
      (2'dC) were detected with UV wavelength set at 267 nm. The standard curves for
      gemcitabine in both matrices ranged from 2 to 200 microM, and for dFdU in plasma,
      from 2 to 100 microM. Within-run and between-run component precision (CV%) was
      <or=6.1 and 5.7%, respectively for both human plasma and tissue culture media,
      and for dFdU, 2.3 and 2.7%. Total accuracy ranged from 98.7 to 106.2% for human
      plasma and from 96.9 to 99.2% for tissue culture media, respectively, and for
      dFdU, from 96.5 to 99.6%. Tetrahydrouridine (THU), an inhibitor of cytidine
      deaminase is used to prevent breakdown in human plasma. With one method we can
      measure gemcitabine in both plasma and tissue culture media. Utility is
      demonstrated by evaluation of the disposition of gemcitabine in an in vitro
      bioreactor cell culture system.

PMID- 16584930
TI  - FOXE1 gene mutation screening by multiplex PCR/DHPLC in CHARGE syndrome and
      syndromic and non-syndromic cleft palate.
AB  - Denaturing high-performance liquid chromatography (DHPLC) has established itself
      as one of the most powerful tools for DNA variation screening. FOXE1, a highly GC
      rich gene involved in syndromic cleft palate, is under investigation in thyroid
      dysgenesis, nonsyndromic cleft palate and squamous cell carcinoma. A technique
      for fast and simultaneous detection of sequence variants in the entire coding
      region of the FOXEl gene based on multiplex PCR/DHPLC is presented here. Given
      its characteristics of high sensitivity and rapidity, the testing strategy
      developed by us appears to be a reliable approach for FOXE1 analysis in the
      screening of a large population at risk.

PMID- 16584932
TI  - Management of acute renal failure in the newborn.
AB  - Acute renal failure is common in the neonatal period. It is usually manifest by
      abnormal biochemistry and decreased urine output (<1 ml/kg/h), but non-oliguric
      renal failure is also common. A detailed understanding of the common
      pathophysiological mechanisms is rarely needed but an understanding of the common
      aetiologies (pre-renal, renal and post-renal) will enable the clinician to
      approach the problem in a logical manner. A standard approach to fluid and
      electrolyte management is described, along with a practical approach to the
      investigation and management of renal failure. A working understanding of the
      principles of peritoneal dialysis is important and a brief overview of the role
      of haemodialysis in neonatal renal failure is provided.

PMID- 16584931
TI  - Main pancreatic duct, common bile duct and sphincter of Oddi structure visualized
      by optical coherence tomography: An ex vivo study compared with histology.
AB  - BACKGROUND: Optical coherence tomography has been proposed to obtain high
      resolution imaging of tissue structure of GI tract. Up till now, the optical
      coherence tomography appearance of the common bile duct, main pancreatic duct and
      sphincter of Oddi wall structure has not yet been defined. AIMS: To compare, in a
      prospective study, optical coherence tomography images of pancreato-biliary
      ductal system with histology and identify the optical coherence tomography
      pattern of the normal wall structure of the ducts. METHODS: Multiple sections of
      non-neoplastic segments of five consecutive ex vivo human pancreatic specimens
      were investigated by optical coherence tomography scanning within 1h of
      resection. Sixty optical coherence tomography images were compared with the
      corresponding histological findings. RESULTS: Optical coherence tomography
      appearance of normal common bile duct, main pancreatic duct and sphincter of Oddi
      is characterized by a differentiated three-layer architecture with a regular
      surface and a homogeneous back-scattered signal, corresponding to the single
      layer of epithelial cells, the connective-muscular layer and the muscular or
      acinar structure, respectively. Optical coherence tomography and histology
      findings were concordant in all cases. CONCLUSIONS: Optical coherence tomography
      was able to provide in real-time images of wall structure of the normal common
      bile duct, main pancreatic duct and sphincter of Oddi that are similar to those
      obtained by histology. These results suggest that optical coherence tomography
      could enable high-resolution images to be obtained from the pancreato-biliary
      system during an ERCP procedure.

PMID- 16584933
TI  - Chemical makeup of microdamaged bone differs from undamaged bone.
AB  - Microdamage naturally occurs in bone tissue as a result of cyclic loading placed
      on the body from normal daily activities. While it is usually repaired through
      the bone turnover process, accumulation of microdamage may result in reduced bone
      quality and increased fracture risk. It is unclear whether certain areas of bone
      are more susceptible to microdamage than others due to compositional differences.
      This study examines whether areas of microdamaged bone are chemically different
      than undamaged areas of bone. Bone samples (L3 vertebrae) were harvested from 15
      dogs. Samples were stained with basic fuchsin, embedded in poly
      methylmethacrylate, and cut into 5-microm-thick sections. Fuchsin staining was
      used to identify regions of microdamage, and synchrotron infrared
      microspectroscopic imaging was used to determine the local bone composition.
      Results showed that microdamaged areas of bone were chemically different than the
      surrounding undamaged areas. Specifically, the mineral stoichiometry was altered
      in microdamaged bone, where the carbonate/protein ratio and carbonate/phosphate
      ratio were significantly lower in areas of microdamage, and the acid phosphate
      content was higher. No differences were observed in tissue mineralization
      (phosphate/protein ratio) or crystallinity between the microdamaged and undamaged
      bone, indicating that the microdamaged regions of bone were not over-mineralized.
      The collagen cross-linking structure was also significantly different in
      microdamaged areas of bone, consistent with ruptured cross-links and reduced
      fracture resistance. All differences in composition had well-defined boundaries
      in the microcrack region, strongly suggesting that they occurred after microcrack
      formation. Even so, because microdamage results in an altered bone composition,
      an accumulation of microdamage might result in a long-term reduction in bone
      quality.

PMID- 16584934
TI  - Renal insufficiency-induced bone loss is associated with an increase in bone size
      and preservation of strength in rat proximal femur.
AB  - Chronic renal insufficiency (CRI) results in phosphate retention and secondary
      hyperparathyroidism, the treatment of which is largely based on the use of
      calcium salts as phosphate binders. Advanced CRI causes bone fragility, but
      information about bone geometry and strength in moderate CRI is scarce. We
      assigned 39 8-week-old male Sprague-Dawley rats to sham-operation (Sham) or 5/6
      nephrectomy (NTX). Four weeks later, the rats were randomized to 0.3% calcium
      (Sham, NTX) or 3.0% calcium diet (Sham + Calcium, NTX + Calcium). After 8 weeks,
      the animals were sacrificed, plasma samples collected, and femora excised for
      neck and midshaft analyses: dual-energy X-ray absorptiometry, peripheral
      quantitative computed tomography, and biomechanical testing. The NTX increased
      plasma urea and PTH 1.6-fold and 3.6-fold, respectively, whereas high calcium
      intake suppressed PTH to 30% of controls. Total femoral bone mineral content
      decreased (-6.3%) in the NTX group, while this deleterious effect was reversed by
      high calcium diet. In the site-specific analysis of the femoral neck, the
      volumetric bone density (-6.5%) was decreased in the NTX group but not NTX +
      Calcium group. However, in the nephrectomized rats, there was also a concomitant
      increase in the cross-sectional area (+15%), and, despite the decrease in bone
      density, the mechanical strength of the femoral neck was maintained. In the
      midshaft, NTX decreased cortical volumetric bone density (-1.2%), but similar to
      the femoral neck, no differences were found in the mechanical strength. In
      conclusion, a decrease in bone mass in moderate experimental CRI was associated
      with a concomitant increase in bone size, and maintenance of mechanical
      competence. Although high calcium diet suppressed plasma PTH to under normal
      physiological levels, it prevented the CRI-induced loss of bone mass without an
      adverse influence on bone strength.

PMID- 16584941
TI  - Dimensionality, internal consistency, and item analysis of the National Health
      and Nutrition Examination Surveys activities of daily living instrument among
      patients with report of low back pain.
AB  - OBJECTIVE: To measure selected psychometric properties of individual item
      responses from the National Health and Nutrition Examination Surveys (NHANES)
      activities of daily living (ADL) instrument among a population of patients with
      low back pain (LBP). METHODS: The study group consisted of 926 individual
      attendees of a traditional medical appointment. All subjects had self-reported
      LBP and completed questions within the NHANES ADL instrument, a 16-item
      questionnaire designed to represent the internal latent construct of ADL. Data
      analyses included exploratory factor analysis, internal consistency measures, and
      polytomous (graded) item response theory. RESULTS: The NHANES ADL instrument is a
      unidimensional and internally consistent measure of ADL. Graded item response
      theory analyses indicated that although some variability exists, all 16 single
      items were sensitive measures of the latent construct of ADL. Most item responses
      demonstrated high discrimination. CONCLUSION: Individual use of selected items of
      the NHANES ADL instrument may further improve the capacity of the health care
      provider in measuring and recording dysfunction associated with LBP.

PMID- 16584938
TI  - Cytochemical, biochemical and molecular aspects of the process of keratinization
      in the epidermis of reptilian scales.
AB  - The characteristics of scaled skin of reptiles is one of their main features that
      distinguish them from the other amniotes, birds and mammals. The different scale
      patterns observed in extant reptiles result from a long evolutive history that
      allowed each species to adapt to its specific environment. The present review
      deals with comparative aspects of epidermal keratinization in reptiles,
      chelonians (turtles and tortoises), lepidosaurian (lizards, snakes,
      sphenodontids), archosaurians (crocodilians). Initially the morphology and
      cytology of reptilian scales is outlined to show the diversity in the epidermis
      among different groups. The structural proteins (alpha-keratins and associated
      proteins), and enzymes utilized to form the corneous layer of the epidermis are
      presented. Aside cytokeratins (alpha-keratins), used for making the cytoskeleton,
      reptilian alpha-keratinocytes produce interkeratin (matrix) and corneous cell
      envelope proteins. Keratin bundles and degraded cell organelles constitute most
      of the corneous material of alpha-keratinocytes. Matrix, histidine-rich and
      sulfur-rich proteins are produced in the soft epidermis and accumulated in the
      cornified cell envelope. Main emphasis is given to the composition and to the
      evolution of the hard keratins (beta-keratins). Beta-keratins constitute the hard
      corneous material of scales. These small proteins are synthesized in beta
      keratinocytes and are accumulated into small packets that rapidly merge into a
      compact corneous material and form densely cornified layers. Beta-keratins are
      smaller proteins (8-20 kDa) in comparison to alpha-keratins (40-70 kDa), and this
      size may determine their dense packing in corneocytes. Both glycine-sulfur-rich
      and glycine-proline-rich proteins have been so far sequenced in the corneous
      material of scales in few reptilian species. The latter keratins possess C- and N
      amino terminal amino acid regions with sequence homology with those of mammalian
      hard keratins. Also, reptilian beta-keratins possess a central core with homology
      with avian scale/feather keratins. Multiple genes code for these proteins and
      their discovery and sequentiation is presently an active field of research. These
      initial findings however suggest that ancient reptiles already possessed some
      common genes that have later diversified to produce the specific keratin
      associated proteins in their descendants: extant reptiles, birds and mammals. The
      evolution of these small proteins in lepidosaurians, chelonians and archosaurians
      represent the next step to understand the evolution of cornification in reptiles
      and derived amniotes (birds and mammals).

PMID- 16584942
TI  - Intensity mapping of pain referral areas in sacroiliac joint pain patients.
AB  - OBJECTIVE: To identify differences in pain referral areas, using intensity maps,
      between responders and nonresponders to a double diagnostic sacroiliac joint
      injection with a short- and long-acting local anesthetic in patients with chronic
      low back pain. METHODS: From a group of 140 consecutive patients with chronic low
      back pain, 60 patients who met clinical criteria were included in the study.
      Twenty-seven demonstrated a positive response to a double diagnostic
      fluoroscopically guided intra-articular sacroiliac joint block and were compared
      with 33 patients with a negative response. Each patient's preinjection pain
      diagram was used to determine areas of pain referral. The summation of these pain
      referral zones for both groups was used to construct intensity maps. RESULTS: No
      major differences were observed between responders and nonresponders with regard
      to mean size and distribution of referral pain areas. Intensity maps, however,
      showed differences in pain referral at the buttock in the areas overlying the
      sacroiliac joint (100% of the responders vs 80% of the nonresponders) and the
      ischial tuberosity (10% of the responders vs 100% of the nonresponders).
      CONCLUSIONS: Overall referred pain maps appeared not to be useful to discriminate
      patients with an identified sacroiliac joint pain from chronic low back pain
      patients with pain from other sources. Differences were only found using
      intensity maps. By implementing these data, it could be concluded that patients
      with sacroiliac joint pain are less likely to experience pain in both the
      'Fortin' and 'tuber' areas. This knowledge can be used as additional selection
      criterion for putative sacroiliac joint patients, next to sacroiliac joint pain
      provocation tests.

PMID- 16584943
TI  - The effect of sacroiliac joint manipulation on feed-forward activation times of
      the deep abdominal musculature.
AB  - OBJECTIVES: To determine the incidence of delayed feed-forward activation (FFA)
      times in a group of healthy young males; to retest those subjects who showed
      delayed FFA after 6 months to determine the reliability of the measure in the
      absence of treatment or injury in the intervening period; and to determine the
      effect of sacroiliac joint manipulation on delayed FFA times. METHODS: Ninety
      young males were assessed for the FFA of their deep abdominal muscles in relation
      to rapid upper limb movements. Those who met the criteria for delayed FFA
      (failure of deep abdominal activation within 50 milliseconds of deltoid
      activation) were then reassessed 6 months later. These subjects then underwent
      sacroiliac joint manipulation on the side demonstrating decreased joint movement
      during hip flexion and lateral flexion. Feed-forward activation times were then
      reassessed after joint manipulation. RESULTS: Seventeen (18.9%) of 90 subjects
      met the criteria of impaired FFA. Thirteen of 17 were available to be remeasured
      at 6-month follow-up. The intraclass correlation coefficient for FFA at this time
      was greater than 0.70 for all movement directions. There was a significant
      improvement (38.4%) in FFA times for this group when remeasured immediately after
      the sacroiliac joint manipulation. CONCLUSIONS: Delayed FFA is a highly
      reproducible measure at long-term follow-up. This technique appears to be a
      sensitive marker of the neural effects of sacroiliac joint manipulation. Future
      prospective studies are needed to determine if delayed FFA times are a marker for
      those at risk for developing back pain.

PMID- 16584944
TI  - Intraexaminer reliability of identifying a dysfunctional segment in the thoracic
      and lumbar spine.
AB  - OBJECTIVE: To examine the intrarater reliability of identifying a manipulable
      lesion in the lumbar and thoracic spine. METHODS: An experienced osteopath used
      dynamic and static examination to assess 12 asymptomatic subjects for signs of
      joint dysfunction in the thoracic and lumbar spine. The selected segment was
      marked with an UV invisible mark. A second examiner visualized these marks with
      an UV lamp and recorded them on acetates for analysis; this process was then
      repeated an hour later. The distance from the marks to a fixed point was measured
      and within-day intrarater reliability was calculated using intraclass correlation
      coefficients (ICCs). RESULTS: The ICC(1,1) for the thoracic spine was 0.70 (95%
      confidence interval [CI], 0.27-0.90). In the lumbar spine the ICC(1,1) was 0.96
      (95% CI, 0.87-0.99). CONCLUSION: This study shows that the lumbar spine joint
      perceived to be the joint most likely to benefit from a high-velocity low
      amplitude thrust can be identified with good within-day reliability in an
      asymptomatic sample using a defined examination protocol. However, the
      reliability in identifying a joint exhibiting signs of segmental dysfunction in
      the thoracic spine was poor.

PMID- 16584946
TI  - Sitting posture of subjects with postural backache.
AB  - OBJECTIVE: To test the construct validity of postural backache. To identify if
      individuals with backache sit for longer periods of sustained sitting and have
      more flexed relaxed sitting posture than individuals in a no backache group.
      METHODS: Following an initial questionnaire, student volunteers without a history
      of 'serious' back pain were classified as either postural backache group or no
      backache group. With the use of an activity diary that plotted activity every 5
      minutes over a 3-day period, the average time spent in different postures was
      established. Relaxed sitting posture was evaluated using Dartfish software to
      analyze videotape after 10 minutes of sitting. RESULTS: The most common daytime
      activity of both groups was sitting, with average sitting time not significantly
      different between groups. Periods of uninterrupted sustained sitting and
      uninterrupted sustained studying were significantly longer, and the degree of
      flexion in relaxed sitting was significantly greater in the postural backache
      group (all P < .024). CONCLUSION: In a group of student volunteers, half reported
      postural backache. The group with backache sat for longer periods without
      interruption and had a more flexed relaxed sitting posture than the no backache
      group. These findings appear to validate McKenzie's concept of a postural
      syndrome.

PMID- 16584945
TI  - Motion palpation of the lumbar spine--a problem with the test or the tester?
AB  - OBJECTIVES: The purpose of this study is to investigate if it is possible to
      recognize whether a specific lumbar motion segment was manipulated or not by
      using motion palpation (MP) as a diagnostic tool in ordinary clinic patients and
      by using teams of practitioners with various levels of experience. METHODS: Two
      teams were created: team A had an experienced doctor of chiropractic who palpated
      the patients and an inexperienced doctor who performed the treatment, whereas
      team B had the opposite composition. One chiropractor in each of the 2 teams
      identified a fixation with the help of MP and specified the treatment of his or
      her choice for this fixation. A few minutes later, the second chiropractor then
      randomly either manipulated or did not manipulate the indicated segment,
      according to the first chiropractor's instruction. Blinded, the first
      chiropractor repalpated the segment and determined whether or not treatment was
      provided. Results were compared with (1) chance findings, (2) the clinicians' own
      pre hoc and specific expectations in relation to the treated cases, and (3) our
      expectation in relation to the untreated cases. RESULTS: Team A failed to reach
      their own standards in relation to treated segments, not even being better than
      chance, and was also unable to detect the untreated cases. The palpating
      chiropractor in team B was able to identify the manipulated segments in 87% of 15
      cases (P < .05) and in 80% of 11 nonmanipulated cases (not significant). The
      successful palpator, therefore, reached the team's general standard of 85%
      success rate but not the specific standard of a 100% success rate. None reached
      our standard of identifying 100% of all untreated segments. CONCLUSION: It is
      possible for some practitioners to identify treated segments using MP. Gold
      standard palpators should therefore be used to calibrate other persons' ability
      to perform MP, both in the clinical setting and in future research studies.

PMID- 16584947
TI  - Plantar infrared thermography measurements and low back pain intensity.
AB  - OBJECTIVE: To study the skin temperature disorders in low back pain (LBP)
      patients compared with reference persons without LBP and to evaluate the
      relationship between pain intensity and other clinical signs and temperature
      abnormalities. METHODS: Sixty-five patients with unilateral chronic LBP with or
      without referred nonradicular leg pain (29 men and 36 women; age range, 30-51
      years) and 20 reference persons without LBP (7 men and 13 women; age range, 30-49
      years) participated in this study. The pain level was recorded by the use of a
      visual analog scale (0-100). Questionnaires and a series of spinal mobility tests
      (the modified Schober, straight leg-raising test, finger-floor distance, side
      bending) were used. Thermographic images of the low back area and legs (anterior,
      lateral, and posterior surfaces and the plantar surfaces of feet) were taken with
      an infrared video camera. RESULTS: The temperature changes in the plantar surface
      correlated with LBP intensity. The pain levels differed in the groups with the
      different types of temperature changes. There were significant lower extremity
      regional skin temperature alterations (at least 1 regional interside difference
      more than 0.3 degrees C) in most cases both in LBP patients and in reference
      persons, but plantar interside temperature difference was significantly higher in
      LBP patients. CONCLUSION: Temperature changes of the plantar surface seem to be
      connected with LBP intensity. Temperature measurements may be useful as an
      adjunctive physiological test in the evaluation and documentation of autonomic
      dysfunction in LBP patients.

PMID- 16584948
TI  - The effects of active release technique on hamstring flexibility: a pilot study.
AB  - OBJECTIVE: The aim of this study is to determine if active release technique
      (ART) significantly increases hamstring flexibility in healthy male participants.
      METHODS: Twenty physically active male participants with no current or previous
      history of lower extremity injury received ART on the origins and insertions of
      the hamstrings and dorsal sacral ligament. The sit-and-reach test was used before
      and after treatment to determine hamstring flexibility. Summary statistics were
      calculated, and pre and post hamstring flexibility scores were compared using a
      related samples t test. RESULTS: There was a significant difference between the
      pre- and posttest groups (mean pre = 35.5 cm, df = 19, SD = 7.56; mean post =
      48.3 cm, df = 19, SD = 7.07; P = .0015). All 20 participants increased their sit
      and-reach scores following the application of ART. CONCLUSIONS: This study
      demonstrated that a single ART treatment increased hamstring flexibility in a
      group of healthy, active male participants.

PMID- 16584949
TI  - Comparative study of hands-on therapy with active exercises vs education with
      active exercises for the management of upper back pain.
AB  - OBJECTIVE: The aim of this study was to compare hands-on therapy, including heat,
      massage, and active exercises with postural education that emphasized increased
      self-efficacy and postural self-awareness along with education about the
      physiology of the disorder, and prescribed daily active exercises. SUBJECTS:
      Twenty-four randomly selected women, 12 custodians and 12 students, with neck and
      shoulder pain and stiffness. METHODS: All subjects received a medical examination
      and x-ray before the study to rule out any pre-existing neurologic deficits and
      an evaluation that included history taking and self-reporting of pain according
      to a numeric pain scale. Student participants received education and exercise
      instructions to be continued daily. The custodial workers received once-per-week
      hands-on treatment. RESULTS: Data were compared using a nonparametric analysis
      (Wilcoxon signed rank test) and showed evidence of statistically significant
      reductions in neck, shoulder, and back stiffness and shoulder muscle tension for
      most of the study subjects. CONCLUSION: Treatment of repetitive stress injuries
      that combines maintenance of daily active exercises prescribed and modeled by a
      professional therapist, which emphasize postural awareness to correct poor
      posture and provide a basic physiological understanding of the disorder, is as
      crucial to reducing upper back and neck pain and stiffness as hands-on therapy
      with active exercise provided in a clinical setting.

PMID- 16584950
TI  - Manipulation in the presence of cervical spinal cord compression: a case series.
AB  - OBJECTIVE: The purpose of this study is to present information from a series of
      patients with imaging findings of encroachment on the cervical spinal cord who
      were treated with chiropractic cervical manipulation. CASE SERIES: There were 27
      patients (18 females, 9 males; age range, 23-65, mean age, 44.3 years) with neck
      and/or arm pain with findings of cervical spinal cord encroachment on magnetic
      resonance imaging. None of these patients had severe or acute myelopathy or
      advanced signal changes in the spinal cord indicative of myelomalacia. These
      patients were treated with a variety of approaches that included some form of
      cervical manipulation. The mean number of treatments that included manipulation
      was 12 (range, 2-32). Nineteen patients were treated with high-velocity, low
      amplitude "thrust" manipulation, 9 patients were treated with low-velocity muscle
      energy technique, and 1 patient was treated with both methods. The mean patient
      rated subjective improvement at the last follow-up reexamination was 70.0%
      (range, 10%-100%). From baseline to the last follow-up examination, the mean
      improvements in outcome measures were as follows: Bournemouth Neck Disability
      Questionnaire, 23.7 points (31%); Neck Disability Index, 6.4 points; and
      Numerical Pain Rating Scale, 3.9 points. In 3 patients, there was increased pain
      after manipulation that lasted from 1 to 4 days. There were no major
      complications, and in no patient did any increased pain after treatment last more
      than 4 days. No new neurologic symptoms or signs were seen in any of these
      patients. CONCLUSION: The finding of cervical spinal cord encroachment on
      magnetic resonance imaging, in and of itself, should not necessarily be
      considered an absolute contraindication to manipulation. However, because
      radicular and myelopathic complications to cervical manipulation have been
      reported in the literature, great care should be taken in all cases, particularly
      those in which anatomic conditions such as cord encroachment are present.

PMID- 16584952
TI  - Adverse reactions to chiropractic care in the UCLA neck pain study: a response.

PMID- 16584951
TI  - Gastroesophageal reflux disease in an 8-year-old boy: a case study.
AB  - OBJECTIVE: To present the diagnosis and management of gastroesophageal reflux
      disease found in a pediatric patient, to discuss the importance of a detailed
      case history, and to bring forward some of the most important clues, both verbal
      and nonverbal, that can lead to the diagnosis. CLINICAL FEATURES: An 8-year-old
      boy was brought to a chiropractic clinic by his mother complaining of headache
      and neck pain. Based on the history and physical examination, a diagnosis of
      cervicogenic headache was made. INTERVENTION AND OUTCOME: Treatment consisted of
      chiropractic manipulation of the upper cervical spine in combination with cranial
      treatment was applied in addition to dietary advice. The headache returned and
      the patient was then referred to a colleague for a second opinion. Based on a
      detailed history, gastroesophageal reflux disease was diagnosed and the patient
      was referred to a specialist for suitable treatment. CONCLUSION: Because of the
      position as first-line health practitioners, it is inevitable that doctors of
      chiropractic will be faced with complaints of a nonbiomechanical nature. It is
      important to recognize conditions, such as gastroesophageal reflux, at an early
      stage and to refer appropriately.

PMID- 16584953
TI  - High-valent iron intermediates in biology.

PMID- 16584956
TI  - Trends in geriatric emergency medicine.
AB  - To better understand future emergency department use, it is valuable to analyze
      the current emergency department use rates of the geriatric population. This
      article reviews emergency department use by demographics, causes of death,
      principal reason for emergency department visits, number of emergency department
      visits per person per year, prescription drugs used, and recent trends in
      emergency department visits.

PMID- 16584957
TI  - Resuscitation of the elderly.
AB  - The changing demographics of America's population over the past couple of decades
      have propelled geriatric medicine into the fore-front. Due to this, emergency
      medicine physicians will face numerous challenges managing an increasing number
      of critically ill elderly patients. This article will focus on success of
      resuscitation in this population, important pathophysiologic changes that occur
      with aging, as well as ethical considerations in end-of-life care.

PMID- 16584958
TI  - Geriatric neurologic emergencies.
AB  - Geriatrics is an important subspecialty within the field of emergency medicine
      and represents a burgeoning area of practice. The special vulnerability of
      elderly patients to neurologic disease and injury and the comparative subtlety of
      clinical presentation mean that physicians should have a lower threshold for
      laboratory studies, radiologic imaging, consultation, and admission. Transferring
      appropriate patients to tertiary centers that offer specialized trauma and
      neurologic and neurosurgical care greatly enhances survival and functional
      outcomes.

PMID- 16584959
TI  - Altered mental status in older emergency department patients.
AB  - This article reviews the significance of altered mental status in older emergency
      department patients. Specific diagnoses are discussed, including delirium, stupor
      and coma, and dementia, with a focus on delirium. Finally, an approach to all
      older patients is suggested that should result in increased clinician comfort
      with older patients, improved ability to communicate with other physicians,
      increased quality of care, and improved patient and family satisfaction.

PMID- 16584960
TI  - Pulmonary emergencies in the elderly.
AB  - The aging process results in changes in pulmonary physiology that make the
      elderly population more susceptible to pulmonary disease. These physiologic
      changes also alter the clinical presentation of such diseases, making the
      diagnosis and treatment of pulmonary disorders particularly challenging for the
      clinician. It is important for the clinician to have a high index of suspicion
      for pulmonary disorders to make the proper diagnosis. It is essential to keep in
      mind the subtle differences between pulmonary diseases in the elderly compared
      with younger patients.

PMID- 16584961
TI  - Cardiovascular emergencies in the elderly.
AB  - Already the major cause of mortality in the United States, cardio-vascular
      emergencies will become increasingly prevalent in the future as the geriatric
      population doubles. This article discusses five cardiovascular emergencies: acute
      coronary syndrome, congestive heart failure, dysrythmias, aortic dissection, and
      ruptured abdominal aortic aneurysm. The discussion focuses on the differences in
      presentation, management, and outcomes that characterize each disease amongst the
      elderly. As a rule, the elderly have significantly worse outcomes than younger
      patients.

PMID- 16584962
TI  - Abdominal pain in the elderly.
AB  - Elderly patients who have abdominal pain remain one of the most challenging
      patient populations. Signs and symptoms of serious disease are often nonspecific.
      Atypical presentations are common in elderly patients. In addition, the higher
      incidence of serious pathology in this population requires emergency physicians
      to be vigilant and thorough in their work-up. Vascular catastrophes are more
      likely to be seen in this population, and a broad differential diagnosis needs to
      be considered.

PMID- 16584964
TI  - Trauma and falls in the elderly.
AB  - The number of people living longer and staying active continues to rise,
      resulting in an increase in the incidence of trauma-related vis-its by older
      persons to emergency departments. The elderly sustain a disproportionate share of
      fractures and serious injury, and represent a unique subset of patients with
      special needs and considerations. This article reviews the current literature on
      the management of elderly patients with trauma, including the physiologic changes
      of aging relevant to the management of trauma, injury patterns unique to
      geriatric victims of trauma, and aspects particular to resuscitation and general
      management of geriatric trauma victims. We include a discussion of the evaluation
      and management of falls in the elderly, including assessment of fall risk.

PMID- 16584965
TI  - Infectious emergencies in the elderly.
AB  - As life expectancy continues to rise, the number of geriatric patients will
      increase and the percentages of geriatric patients seen in the emergency
      department will reflect those numbers. Emergency physicians are responsible for
      making immediate diagnoses and initiating expeditious treatment. Infectious
      diseases in the elderly are more prevalent, challenging to diagnose, and are
      associated with greater morbidity and mortality than with the younger patient
      population.

PMID- 16584963
TI  - Atraumatic joint and limb pain in the elderly.
AB  - Patients who visit the emergency department often have complaints of joint and
      limb pain. The differential diagnosis, clinical presentation, and treatment
      choices can be vastly different in the young- or middle-aged population compared
      with the elderly population, and the concerns of each group must be addressed.
      The emergency physician is in a unique position in that they are frequently the
      first to see these individuals and have the opportunity to intervene before
      permanent disability ensues. Some of the more common etiologies of atraumatic
      joint and limb pain, including crystal deposition diseases such as gout and
      pseudogout, osteoarthritis, septic arthritis, and inflammatory arthritides such
      as rheumatoid arthritis will be addressed in this article. In addition,several
      arthritides specific to the elderly population such as poly-myalgia rheumatica
      and associated giant cell arteritis will be covered. Finally a discussion of
      cervical and lumbar disc disease, as well as gait disorders, and their impact on
      the elderly, will be presented.

PMID- 16584966
TI  - Pharmacologic issues in geriatric emergency medicine.
AB  - The challenge for the practitioner is to balance incomplete evidence about
      efficacy of medications in frail older people against the problems related to
      adverse drug reactions without denying people potentially valuable
      pharmacotherapeutic interventions. Prescribers need to be diligent in reviewing
      medications periodically as well as when new medications are being considered.
      Review of updated explicit criteria is essential to understand and prescribe
      appropriately in this special population.

PMID- 16584967
TI  - Psychiatric emergencies in the elderly population.
AB  - This article reviews the most common behavioral emergencies in the geriatric
      population. Psychiatric emergencies are seen frequently by emergency physicians
      who face the challenge of assessing and managing patients presenting with
      psychosis, severe depression, agitation, suicidal intent, and substance abuse in
      the emergency department. The evaluation is frequently complicated by the
      necessity to investigate numerous domains such as underlying medical conditions,
      prior psychiatric disorders and substance abuse, as well as psychosocial factors.
      It is crucial to rule out organic causes for what appears to be psychiatric
      disease in the elderly. The assessment might be further complicated by the
      patient's limited ability to recall pertinent aspects of the history due to
      either cognitive impairment or acute distress. Emergency department personnel
      might have inadequate expertise in assessing emergencies in elderly persons,
      further impeding the ability to appropriately manage behavioral complications in
      geriatric patients. Availability of high-quality emergency care and tight
      collaboration with primary care providers, psychiatric consultants, and social
      services is crucial to optimal outcomes from acute psychiatric decompensations in
      the elderly.

PMID- 16584968
TI  - Elder abuse.
AB  - Elder abuse and neglect is a prevalent, underrecognized problem among today's
      senior citizens. Fortunately, awareness is increasing, and services are being
      provided to elders on a more ready basis. Still, the emergency care provider must
      act as a patient advocate and assume responsibility for the detection, treatment,
      and safe disposition of unfortunate victims.

PMID- 16584969
TI  - The beer campaign in Stockholm--Attempting to restrict the availability of
      alcohol to young people.
AB  - A number of Swedish studies have indicated that it is easy for underaged youths
      to purchase medium strength beer in grocery shops. The aim of this study was to
      follow the effects of a community action-based intervention involving
      information/training of parents, police, and shopkeepers, media advocacy, and
      monitoring of the sales of beer to underaged youths. Eighteen-year-old students,
      looking younger, attempted to purchase a six-pack of medium strength beer in
      grocery shops without showing ID. A questionnaire about perceived availability
      was distributed among ninth-grade students. Surveys of parental awareness and
      shopkeepers' attitudes were also conducted. A significant decrease in sales was
      observed in both the intervention area (from 73% of all purchase attempts to 44%)
      and in the comparison area (from 60% to 44%). No significant difference was found
      between the intervention and the comparison areas, in part due to a contamination
      effect in the comparison area, where similar activities were conducted by the
      local community. Perceived availability by teenagers did not change. Following
      the intervention, availability to medium strength beer for young people in the
      intervention area decreased, but remained high. It is possible that this moderate
      reduction was due to the intervention but the same is not certain, given the
      developments in the comparison area. The intervention was primarily based on
      information and training, whereas a policy of surveillance and sanctions in the
      comparison area appears to have achieved the same result, with lesser resources.
      The study also illustrates the feasibility of engaging parents in community
      action for prevention purposes.

PMID- 16584970
TI  - Alcohol consumption and plasma homocysteine.
AB  - A few reports show that consumption of spirits and of wine correlate with
      elevated plasma total homocysteine (tHcy), which is associated with the risk of
      cardiovascular disease. We analyzed the relation between tHcy and current daily
      ethanol consumption cross-sectionally in middle-aged Japanese men (n = 974, age
      51-59 years). Plasma tHcy was positively associated with consumption of whiskey
      but not with consumption of shochu (Japanese spirits), sake, beer, or wine. Odds
      ratios of an increase in daily intake of 30 ml ethanol (approximately 1 standard
      deviation) for hyperhomocysteinemia (>14.0 micromol/l) were 2.58 (95% confidence
      interval, 1.29-5.14) for whiskey, 1.08 (0.78-1.50) for shochu, 0.99 (0.59-1.66)
      for sake, 0.98 (0.58-1.63) for beer, and 1.70 (0.31-9.50) for wine in a
      multivariate logistic regression analysis adjusted for the daily number of
      cigarettes smoked, physical activity, vegetable consumption, and serum creatinine
      levels. After inclusion of plasma folate and vitamin B12 in the multivariate
      analysis model, the association between whiskey ethanol consumption and
      hyperhomocysteinemia remained significant with odds ratio of 2.79 (1.36-5.72).
      These results suggest that whiskey consumption correlates with
      hyperhomocysteinemia independently of plasma folate or vitamin B12 or lifestyle
      factors in the population studied.

PMID- 16584971
TI  - Long-term effects of neonatal alcohol exposure on photic reentrainment and phase
      shifting responses of the activity rhythm in adult rats.
AB  - In rats, neonatal alcohol (EtOH) exposure coinciding with the period of rapid
      brain growth produces structural damage in some brain regions that often persists
      into adulthood and thus may have long-term consequences in the neural regulation
      of behavior. Because recent findings indicate that the circadian clock located in
      the rat suprachiasmatic nucleus is vulnerable to alcohol-induced insults during
      development, the present study examined the long-term effects of neonatal alcohol
      exposure on the photic regulation of circadian behavior in adult rats. Rat pups
      were exposed to alcohol (3.0, 4.5, or 6.0 g x kg(-1) x day(-1)) or isocaloric
      milk formula on postnatal days 4-9 using artificial-rearing methods. At 2 months
      of age, animals were housed individually and circadian wheel-running behavior was
      continuously analyzed to determine the effects of neonatal alcohol treatment on
      the rate of reentrainment to a 6-h advance in the 12-h light:12-h dark
      photoperiod and the phase-shifting properties of free-running rhythms in response
      to discrete light pulses on a background of constant darkness. For all doses,
      neonatal alcohol exposure had a significant effect in reducing the time for
      reentrainment such that EtOH-treated rats required four to five fewer days than
      control animals for stable realignment of the activity rhythm to the shifted
      light-dark cycle. Coupled with the accelerated rate of reentrainment, the
      amplitude of light-evoked phase delays at circadian time 14 and advances at
      circadian time 22 in the 4.5 and 6.0 g x kg(-1) x day(-1) EtOH groups was almost
      twofold greater than that observed in control animals. The present observations
      indicate that the mechanisms by which photic signals regulate circadian behavior
      are permanently altered following alcohol exposure during the period of rapid
      brain development. These long-term alterations in the photic regulation of
      circadian rhythms may account, at least partially, for some neurobehavioral
      consequences of prenatal alcohol exposure in humans such as depression.

PMID- 16584972
TI  - Green tea supplementation in rats of different ages mitigates ethanol-induced
      changes in brain antioxidant abilities.
AB  - Oxidative stress induced by chronic ethanol consumption, particularly in aging
      subjects, has been implicated in the pathophysiology of many neurodegenerative
      diseases. Antioxidants with polyphenol structures, such as those contained in
      green tea, given alone for 5 weeks in liquid Lieber de Carli diet followed by
      administration with ethanol for 4 weeks with ethanol have been investigated as
      potential therapeutic antioxidant agents in the brain in rats of three ages (2,
      12, and 24 months). Ethanol consumption caused age-dependent decreases in brain
      superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase
      activities. In addition, ethanol consumption caused age-dependent decreases in
      the levels of GSH, selenium, vitamins, E, A and C, and beta-carotene and
      increases in the levels of oxidized glutathione (GSSG). Changes in the brain's
      antioxidative ability were accompanied by enhanced oxidative modification of
      lipids (increases in lipid hydroperoxides, malondialdehyde, and 4-hydroxynonenal
      levels) and proteins (increases in carbonyl groups and bistyrosine). Reduced risk
      of oxidative stress and protection of the central nervous system, particularly in
      young and adult rats, after green tea supplementation were observed. Green tea
      partially prevented changes in antioxidant enzymatic as well as nonenzymatic
      parameters induced by ethanol and enhanced by aging. Administration of green tea
      significantly protects lipids and proteins against oxidative modifications in the
      brain tissue of young and adult rats. The beneficial effect of green tea can
      result from the inhibition of free radical chain reactions generated during
      ethanol-induced oxidative stress and/or from green tea-induced increases in
      antioxidative abilities made possible by increases in the activity/concentration
      of endogenous antioxidants.

PMID- 16584973
TI  - Increased brain dopamine D4-like binding after chronic ethanol is not associated
      with behavioral sensitization in mice.
AB  - Dopaminergic D4 receptors have been hypothesized to be involved in
      neuropsychiatric disorders and substance abuse. In mice, repeated ethanol
      administration may induce behavioral sensitization, a phenomenon of increased
      sensitivity to the drug's stimulant properties. This study aimed to analyze brain
      D4 receptors binding in mice with different levels of behavioral sensitization to
      ethanol. Male Swiss mice received 2.2 g/kg ethanol (n = 64) or saline (n = 16)
      intraperitoneally daily for 21 days and were weekly tested for locomotor activity
      and for blood ethanol levels. According to the locomotor scores presented across
      test days, ethanol-treated mice were classified as "sensitized" or
      "nonsensitized." Twenty-four hours after the last administration, mice were
      sacrificed and brains were processed for autoradiography. Brain D4 binding was
      assessed by quantitative autoradiography using [3H]nemonapride + raclopride in
      three groups: saline-treated controls (n = 10), ethanol-sensitized (n = 11), and
      ethanol-nonsensitized (n = 9) mice. Both sensitized and nonsensitized mice showed
      higher D4 binding densities than saline-treated controls in the posterior caudate
      putamen and the olfactory tubercle (p < .02), but only sensitized mice presented
      higher D4 binding than controls at the lateral septal nucleus (p < .02). However,
      there were no differences between sensitized and nonsensitized mice in any of the
      brain regions analyzed. Furthermore, sensitized and nonsensitized mice presented
      similar blood ethanol levels during the treatment. The higher D4 binding levels
      observed in both ethanol-treated subgroups (sensitized and nonsensitized) suggest
      that chronic ethanol treatment may induce upregulation of D4 receptors in
      specific brain regions. However, this mechanism does not seem to be associated
      with the differential ability to develop behavioral sensitization to ethanol in
      mice.

PMID- 16584974
TI  - Effect of ethanol on follicle stimulating hormone-induced steroidogenic acute
      regulatory protein (StAR) in cultured rat granulosa cells.
AB  - Steroidogenic acute regulatory protein (StAR) plays a critical role in trophic
      hormone-stimulated steroid biosynthesis by facilitating the transfer of
      cholesterol across the mitochondrial membrane, where the cytochrome P450scc
      enzyme resides to initiate steroid hormone biosynthesis. Because follicle
      stimulating hormone (FSH) is a critically important regulator of estradiol (E2)
      synthesis in granulosa cells and because ethanol is known to suppress
      gonadotropin-stimulated ovarian steroidogenesis, we evaluated the effects of
      ethanol on FSH-stimulated StAR in ovarian granulosa cells. Granulosa cells from
      immature rats pretreated with pregnant mare serum gonadotropin were cultured for
      24 h in serum-free medium, either alone (medium only) or with FSH (25 ng/ml) in
      the presence or absence of ethanol (50 mM). Real-time polymerase chain reaction
      (PCR) analysis showed increased (p < 0.01) expression of the StAR transcript in
      FSH-treated cells, when compared with cells that received medium only. The FSH
      stimulation of StAR transcript was blocked (p < 0.01) by the presence of ethanol.
      This effect coincided with a decrease in E2 secretion into the culture medium. We
      also examined whether ethanol could affect the production of cyclic AMP (cAMP),
      the main second messenger that mediates gonadotropin action within the ovary. FSH
      treatment of granulosa cells markedly increased (p < 0.001) cAMP levels, an
      effect that was not altered by ethanol. Importantly, FSH induced an increase (p <
      0.01) in the release of prostaglandin E2 (PGE2), an effect that was blocked by
      ethanol. Real-time PCR analysis showed that ethanol had no effect on the
      expression of cyclooxygenase-1 (COX-1), but blocked (p < 0.01) FSH-stimulated
      expression of COX-2. These results demonstrate that ethanol is capable of
      inhibiting FSH-induced ovarian StAR and thus, contributing to suppressed E2
      secretion, at least in part, through an inhibitory action on the COX-2-PGE2
      pathway.

PMID- 16584975
TI  - Rib fractures in chronic alcoholic men: Relationship with feeding habits, social
      problems, malnutrition, bone alterations, and liver dysfunction.
AB  - Rib fractures are common in alcoholics. This high prevalence might be due to
      ethanol-associated malnutrition, bone disease, liver dysfunction, or the peculiar
      lifestyle of the alcoholic with frequent trauma and altercations. In this study
      we try to discern the role of these factors on rib fracture (assessed on a plain
      thoracic X-ray film) in 81 consecutive alcoholic patients, 25 of them cirrhotics.
      Serum albumin, prothrombin aspartate aminotransferase (ASAT), alanine
      aminotransferase (ALAT), gamma-glutamyl transpeptidase, C-terminal cross-linking
      telopeptide of type 1 collagen, osteocalcin, insulin growth factor 1, 1,25
      dihydroxyvitamin D, parathyroid hormone, estradiol, free testosterone, and
      corticosterone were measured, and the patients also underwent assessment of bone
      mineral density by a HOLOGIC QDR-2000 bone densitometer (Waltham, MA, USA). Body
      mass index, triceps skinfold, and brachial perimeter were also determined, and
      the patients and their families were asked about tobacco consumption, social and
      familial links, consumption of ethanol by other members of the family, kind of
      job, and feeding habits. Forty-two male nondrinker sanitary workers of similar
      age served as controls. Forty of the 81 patients showed rib fractures. There was
      a statistically significant association between rib fractures and disruption of
      social and familial links, irregular feeding habits (in bars or pubs, not at
      home), ethanol consumption by close relatives, and intensity of tobacco
      consumption, but not between rib fractures and liver function tests, nutritional
      parameters, or bone mineral density, besides a nearly significant trend (p =
      .053) with the presence of osteopenia at the femoral neck. Patients with major
      withdrawal symptoms at admission also presented more frequent rib fractures. We
      conclude that rib fractures in alcoholics are related to the peculiar lifestyle
      of these patients rather than to bone alterations, liver dysfunction, or
      nutritional status.

PMID- 16584976
TI  - A framework for evaluating image segmentation algorithms.
AB  - The purpose of this paper is to describe a framework for evaluating image
      segmentation algorithms. Image segmentation consists of object recognition and
      delineation. For evaluating segmentation methods, three factors-precision
      (reliability), accuracy (validity), and efficiency (viability)-need to be
      considered for both recognition and delineation. To assess precision, we need to
      choose a figure of merit, repeat segmentation considering all sources of
      variation, and determine variations in figure of merit via statistical analysis.
      It is impossible usually to establish true segmentation. Hence, to assess
      accuracy, we need to choose a surrogate of true segmentation and proceed as for
      precision. In determining accuracy, it may be important to consider different
      'landmark' areas of the structure to be segmented depending on the application.
      To assess efficiency, both the computational and the user time required for
      algorithm training and for algorithm execution should be measured and analyzed.
      Precision, accuracy, and efficiency factors have an influence on one another. It
      is difficult to improve one factor without affecting others. Segmentation methods
      must be compared based on all three factors, as illustrated in an example wherein
      two methods are compared in a particular application domain. The weight given to
      each factor depends on application.

PMID- 16584977
TI  - Lille Conference talk.

PMID- 16584978
TI  - Nuclear envelope proteins and chromatin arrangement: a pathogenic mechanism for
      laminopathies.
AB  - The involvement of the nuclear envelope in the modulation of chromatin
      organization is strongly suggested by the increasing number of human diseases due
      to mutations of nuclear envelope proteins. A common feature of these diseases,
      named laminopathies, is the occurrence of major chromatin defects. We previously
      reported that cells from laminopathic patients show an altered nuclear profile,
      and loss or detachment of heterochromatin from the nuclear envelope. Recent
      evidence indicates that processing of the lamin A precursor is altered in
      laminopathies featuring pre-mature aging and/or lipodystrophy phenotype. In these
      cases, pre-lamin A is accumulated in the nucleus and heterochromatin is severely
      disorganized. Here we report evidence indicating that pre-lamin A is mis
      localized in the nuclei of Emery-Dreifuss muscular dystrophy fibroblasts, either
      bearing lamin A/C or emerin mutations. Abnormal pre-lamin A-containing structures
      are formed following treatment with a farnesyl-transferase inhibitor, a drug that
      causes accumulation of pre-lamin A. Pre-lamin A-labeled structures co-localize
      with heterochromatin clumps. These data indicate that in almost all laminopathies
      the expression of the mutant lamin A precursor disrupts the organization of
      heterochromatin domains. Our results further show that the absence of emerin
      expression alters the distribution of pre-lamin A and of heterochromatin areas,
      suggesting a major involvement of emerin in pre-lamin A-mediated mechanisms of
      chromatin remodeling.

PMID- 16584979
TI  - Nuclear expression of diacylglycerol kinases: possible involvement in DNA
      replication.
AB  - The existence of intranuclear lipid-dependent signal transduction systems has
      been demonstrated by several independent groups. Remarkably, intranuclear lipid
      dependent signal transduction pathways are regulated independently from their
      membrane/cytosolic counterparts. A sizable body of evidence suggests that nuclear
      lipid signaling controls critical biological functions such as cell
      proliferation, differentiation, and apoptosis. Diacylglycerol (DG) is a
      fundamental lipid second messenger which is produced in the nucleus. Since the
      levels of nuclear DG fluctuate during the cell cycle progression, it has been
      suggested that this lipid second messenger has important regulatory roles. Most
      likely, nuclear DG serves as a chemoattractant for some isoforms of protein
      kinase C that migrate to the nucleus in response to a variety of agonists. The
      nucleus also contains diacylglycerol kinases (DGKs), i.e. the enzymes that, by
      converting DG into phosphatidic acid (PA), terminate DG-dependent events. This
      review aims at highlighting the different isozymes of DGKs present within the
      nucleus as well as at discussing their potential functions with particular
      emphasis placed on DNA replication.

PMID- 16584981
TI  - Involvement of cdks and cyclins in muscle differentiation.
AB  - Myocyte differentiation is due to transcription of genes that characterize the
      phenotypic and biochemical identity of differentiated muscle cells. These are the
      myogenic regulatory factors (MRFs) MyoD, Myf5, myogenin and MRF4. Overexpression
      of cdk/cyclins has been reported to inhibit the activity of MyoD and prevent
      myogenic differentiation by different modalities. Unlike other cdk/cyclin
      complexes, overexpression of cdk9/cyclin T2a, enhances MyoD function and promotes
      myogenic differentiation. In addition, cyclin T2a interacting with a novel
      partner, PKN alpha, is able to strongly enhance the expression of myogenic
      differentiation markers, such as myogenin and Myosin Heavy Chain. So, cyclin T2a
      could stimulate myogenic differentiation interacting with different kinase
      partners Cdk9 or PKN alpha in a synergistic or antagonistic way.

PMID- 16584980
TI  - TNF-related apoptosis-inducing ligand (TRAIL) and erythropoiesis: a role for PKC
      epsilon.
AB  - The regulation of the hematopoietic stem cell pool size and the processes of cell
      differentiation along the hematopoietic lineages involve apoptosis. Among the
      different factors with a recognized activity on blood progenitor cells, TRAIL - a
      member of the TNF family of cytokines - has an emerging role in the modulation of
      normal hematopoiesis.PKC(epsilon) levels are regulated by EPO in differentiating
      erythroid progenitors and control the protection against the apoptogenic effect
      of TRAIL. EPO-induced erythroid CD34 cells are insensitive to the apoptogenic
      effect of TRAIL between day 0 and day 3, due to the lack of specific surface
      receptors expression. Death receptors appear after day 3 of differentiation and
      consequently erythroid cells become sensitive to TRAIL up to day 9/10, when the
      EPO-driven up-regulation of PKC epsilon intracellular levels inhibits the TRAIL
      mediated apoptosis, via Bcl-2. In the time interval between day 3 and 9,
      therefore, the number of erythroid progenitors can be limited by the presence of
      soluble or membrane-bound TRAIL present in the bone marrow microenvironment.

PMID- 16584982
TI  - The value of immunohistochemical research on PCNA, p53 and heat shock proteins in
      prostate cancer management: a review.
AB  - This review addresses the significance of the expression of proliferating cell
      nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate
      carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC
      diagnosis, mainly because of the controversy regarding the significance of their
      expression during prostate cancer development and progression. At the same time,
      only few studies have shown the potential role of Hsps in carcinogenesis and
      their overexpression in pre-neoplastic and neoplastic lesions of the prostate. We
      briefly describe the physiological roles of Hsps in normal cells, and the
      significance of their immunohistochemical detection in PC as well as in pre
      cancerous lesions of the prostate. We will also discuss the possible functional
      interactions of these molecules in both dysplastic and neoplastic cells.

PMID- 16584983
TI  - Nuclear bodies domain changes with microspore reprogramming to embryogenesis.
AB  - We analysed the presence of nuclear bodies and particularly Cajal bodies during
      representative stages of gametophytic and haploid embryogenic development in
      isolated microspore and anther cultures of a model system (Brassica napus cv.
      Topas) and a recalcitrant species (Capsicum annuum L. var. Yolo Wonder B). The
      nuclear bodies domain is involved on several important roles on nuclear
      metabolism, and Cajal bodies are specifically involved on the storage and
      maturation of both snRNPs and snoRNPs, as well as other splicing factors,
      necessary for mRNA and pre-rRNA processing, but not directly on the
      transcription. In this study, immunofluorescence and immunogold labelling with
      anti-trimethylguanosine antibodies against the specific cap of snRNAs,
      ultrastructural and cytochemical analysis were performed on cryoprocessed samples
      at confocal and electron microscopy respectively. Results showed that Cajal
      bodies increase during the early stages of microspore embryogenic development
      (young pro-embryos), compared to microspore and pollen development. Our results
      suggest that Cajal bodies may have a role in the transcriptionally active,
      proliferative stages that characterise early microspore embryogenic development.

PMID- 16584984
TI  - Quantity of AgNORs in gastric endocrine carcinoid tumours as a potential
      prognostic tool.
AB  - In order to assess if the quantity of silver-stained nucleolar organizer region
      (AgNOR) proteins represents a prognostic tool in gastric carcinoids, a
      standardised AgNOR analysis was performed on 24 samples collected from the
      pathology archives of the Universities of Messina and Parma; the samples were
      taken at surgery from 11 males and 13 females (mean age 55 yrs, age range 28-77
      yrs); 13 cases were defined as Type I, 1 case as Type II and 10 cases as Type
      III; 16 cases showed a diameter <1 cm, 8 >1 cm. Only 6 tumours were deeply
      invasive, breaking through the muscularis propria or the subserosa. The
      proliferative status of carcinoids performed by Ki67 protein antibodies was
      available in 20/24 cases. The quantification of AgNORs was performed according to
      the guidelines of the Committee on AgNOR Quantification and the mean area
      (microm2) of AgNORs per nucleus (NORA) was determined by means of image analyser
      and specific software programs. The relationship between NORA values and Ki67
      data was investigated by Spearman correlation test. The mean NORA value of all 24
      gastric carcinoids was 1.279 microm2 (SD 0.404); values ranged from 0.734 to
      2.142 microm2. A significantly higher (p < 0.001) mean NORA value (1.736 microm2;
      SD 0.283) was found in tumours larger than 1 cm, in comparison to the smaller
      neoplasms (1.051 microm2; SD 0.214); moreover, cases showing deep wall invasion
      exhibited a mean NORA value of 1.765 microm2 (SD 0.276), significantly higher (p
      < 0.001) than those with superficial growth (1.118 microm2; SD 0.296). Finally, a
      similar highly significant difference was seen between type III carcinoids (1.615
      microm2; SD 0.375) and type I-II (1.040 microm2; SD 0.208). A linear relationship
      between Ki67 and corresponding NORA values was obtained by the Spearman
      correlation test (p = 0.001). No other significant correlations were found
      between mean NORA values and other clinico-pathological parameters. The AgNOR
      method seems to be an additional tool potentially able to predict the prognosis
      of this kind of endocrine tumour, facilitating the identification of fast-growing
      tumours and being able to directly correlate with the size, deep invasion of
      gastric wall and tumour type, generally considered as the best prognostic
      indicators.

PMID- 16584985
TI  - Prostatic stromal microenvironment and experimental diabetes.
AB  - The diabetes causes alterations in various organ systems, including the male
      accessory sex glands. The prostate is very important in the reproductive process
      and it is a frequent target of malignant changes. The aim of this work was to
      demonstrate the histochemical and ultrastructural alterations in the prostate of
      diabetic animals. Two groups of animals were utilized: control and non-obese
      diabetic mice (NOD). Twelve days after the characterization of diabetic status
      the ventral prostate was collected, fixed in Karnovsky and paraformaldehyde,
      processed for histochemistry and TEM associated to stereology. The results showed
      reduction of the epithelial area and increasing of the stromal area with muscular
      and collagen hypertrophy in the prostatic gland. It was characterized the
      development of prostatic intraepithelial neoplasia, inflammatory processes and
      dilation of the organelles involved in the secretory process. It was concluded
      that diabetes besides damaging the reproductive process, affects the glandular
      homeostasis favoring the development of prostatic pathologies.

PMID- 16584987
TI  - Effects of partial decerebration and hypophyseal allograft in the thymus of
      chicken embryos: thymostimulin localization and enzymatic activities.
AB  - Changes in chicken embryo thymus after partial decerebration (including the
      hypophysis) and hypophyseal allograft were investigated. Chicken embryos were
      partially decerebrated at 36-40 hr of incubation and on day 12 received a
      hypophyseal allograft from 18-day-old donor embryos. The embryonic thymuses were
      collected on day 18 and examined with histological methods, tested for the anti
      thymostimulin-like immune-reaction, and for histoenzymatic activities and
      compared with normal and sham-operated embryos at the same age. After partial
      decerebration, the thymic cortical and medullary compartments diminished markedly
      in size. Anti-thymostimulin, succinic dehydrogenase and ATPase enzymatic
      activities tested, yielded negative reactions. In partially decerebrated
      hypophyseal allografted embryos, the same thymic compartments improved and anti
      thymostimulin-like immune-reaction and enzymatic activities partially recovered.
      These findings confirmed the key role of hypophysis in thymic ontogenic
      development and provided new information in metabolic enzymatic pathways and
      synthesis of a thymostimulin-like substance in the thymus.

PMID- 16584986
TI  - An immunohistochemical study of the pancreatic endocrine cells of the nude mouse,
      Balb/c-nu/nu.
AB  - The regional distribution and frequency of the pancreatic endocrine cells in the
      nude mouse, Balb/c-nu/nu were studied by immunohistochemical (peroxidase anti
      peroxidase; PAP) methods using specific antisera against insulin, glucagon,
      somatostatin and human pancreatic polypeptide (hPP). The pancreas of the mouse
      was divided into two lobes, the splenic and duodenal lobes, and each lobe was
      subdivided into three regions, the pancreatic islets (central and peripheral
      regions), the exocrine region and the pancreatic duct region (consisting of duct
      epithelium and surrounding connective tissue--sub-epithelial connective tissue).
      In the pancreatic islets, most of insulin-immunoreactive (IR) cells were located
      in the central region, and glucagon-, somatostatin and hPP-IR cells were located
      in the peripheral region regardless of the lobe. In the splenic part, glucagon-IR
      cells were also located in the central regions, and more numerous somatostatin-IR
      cells were detected in the central regions compared to those of the duodenal
      part. hPP-IR cells were restricted to the peripheral regions in both lobes but
      more numerous cells were detected in the duodenal portion as compared to those of
      the splenic portion. In the exocrine parenchyma of the splenic lobe, only insulin
      , glucagon- and somatostatin-IR cells were detected.. Here, the insulin- and
      glucagon-IR cells formed cell clusters, while somatostatin-IR cells were present
      as solitary cells. In the exocrine region of the duodenal portion, only insulin-,
      somatostatin- and hPP-IR cells were observed, with the same distributional
      pattern as that found in the splenic lobe. However, clusters of cells consisting
      only of hPP-IR cells were distributed in the pancreas parenchyma as small islets.
      In the pancreatic duct region, only solitary hPP-IR cells were demonstrated in
      the sub-epithelial connective tissue regions of the splenic portion. In
      conclusion, some strain-dependent characteristic distributional patterns of
      pancreatic endocrine cells, especially of the hPP-IR cells, were found in the
      nude mouse. In addition, somewhat different distributional patterns were found
      between the two pancreatic lobes.

PMID- 16584988
TI  - Nuclear histochemistry: Its history in fifty volumes.

PMID- 16584989
TI  - Effects of blood withdrawal and reinfusion on biomarkers of erythropoiesis in
      humans: Implications for anti-doping strategies.
AB  - To discriminate autologous blood doping procedures from normal conditions, we
      examined the hematological response to blood withdrawal and reinfusion. We found
      that biomarkers of erythropoiesis are primarily affected in the anemic period.
      Therefore, individual variations in [Hb] exceeding 15% between samples obtained
      shortly before any major competition would be indicative of autologous blood
      manipulation.

PMID- 16585010
TI  - The place of positron emission tomography imaging in the management of patients
      with malignant lymphoma.

PMID- 16585011
TI  - The effect of prior exposure to imatinib on transplant-related mortality.
AB  - BACKGROUND AND OBJECTIVES: Imatinib is an effective treatment for chronic myeloid
      leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic
      leukemia (ALL). However, relapse is common in patients with advanced or high risk
      disease. Such patients may be eligible for allogeneic stem cell transplantation
      (SCT), raising the question whether imatinib therapy may compromise the outcome
      of subsequent SCT. DESIGN AND METHODS: We retrospectively analyzed 70 patients
      with CML and 21 with Ph+ ALL who had received imatinib prior to SCT. Data were
      retrieved by directly contacting centers. Multivariate analysis was used to
      define factors associated with major outcomes (engraftment, graft-versus-host
      disease, relapse, non-relapse mortality) in addition to descriptive statistics.
      For the CML patients major outcomes were compared with those of historical
      controls drawn from the EBMT registry. RESULTS: At SCT, 44% of CML patients were
      in accelerated phase or blast crisis and 40% of ALL patients had active disease
      compared to 84% and 95% prior to imatinib. At 24 months, estimated transplant
      related mortality was 44% and estimated relapse mortality 24%. Factors associated
      with shorter overall and progression-free survival were advanced disease at SCT
      and a female donor/male recipient pairing. No unusual organ toxicities were
      observed. Compared to historical controls, prior imatinib treatment did not
      influence overall survival, progression-free survival or non-relapse mortality,
      while there was a trend towards higher relapse mortality and significantly less
      chronic graft-versus-host disease. INTERPRETATION AND CONCLUSIONS: Within the
      limits of a heterogeneous and relatively small cohort of patients, we found no
      evidence that imatinib negatively affects major outcomes after SCT, suggesting
      that imatinib prior to SCT is safe.

PMID- 16585009
TI  - Cold agglutinin disease.

PMID- 16585012
TI  - Primary chronic cold agglutinin disease: a population based clinical study of 86
      patients.
AB  - BACKGROUND AND OBJECTIVES: Our knowledge of primary chronic cold agglutinin
      disease (CAD) is incomplete. The aim of this study was to collect comprehensive
      and precise data the on epidemiology, clinical and pathological features, course,
      and therapy of CAD. DESIGN AND METHODS: We performed a population-based
      retrospective follow-up study of as many as possible of all CAD patients in
      Norway. Eighty-six patients were studied. RESULTS: The prevalence of primary CAD
      was 16 cases per million inhabitants. The incidence rate was 1 per million per
      year. The median age at onset was 67 years (range, 30-92) and the male to female
      ratio was 0.55. The median survival was 12.5 years from onset. Autoimmune
      diseases other than CAD were reported in 8% of patients, cold-induced circulatory
      symptoms in 91%, and exacerbation of hemolytic anemia during febrile illness in
      74%. At least 51% had received red blood cell transfusions. The mean initial
      hemoglobin level was 9.2 g/dL (range, 4.5-15.6) and the median monoclonal
      immunoglobulin level 4.0 g/L (range, 0.0-47.3). Most laboratory findings did not
      change significantly during a median follow-up of 5 years. Monoclonal IgM was
      detected in 90%; IgG and IgA in 3.5% each; with kappa light chains in 94%. An
      abnormal kappa/lambda ratio in bone marrow was found in 90%, lymphoma in 76%, and
      lymphoplasmacytic lymphoma in 50%. Transformation to aggressive lymphoma occurred
      in 3.5% during 10 years. Rituximab therapy was the only treatment showing
      acceptable response rates (60%). INTERPRETATION AND CONCLUSIONS: Primary CAD
      represents a spectrum of clonal lymphoproliferative bone marrow disorders, in
      most cases with morphological signs of lymphoma. Despite a favorable prognosis
      for survival, the disease is not indolent in terms of clinical manifestations.

PMID- 16585013
TI  - PRDM1/BLIMP-1 expression in multiple B and T-cell lymphoma.
AB  - BACKGROUND AND OBJECTIVES: The positive regulatory domain I (PRDM1) protein or
      BLIMP-1, belonging to the PRDM gene family of transcriptional repressors, is a
      key regulator of terminal differentiation in B-lymphocytes and is critical for
      plasma cell differentiation. DESIGN AND METHODS: Here we document the expression
      of PRDM1 in normal and neoplastic lymphoid cells, through the use of a monoclonal
      antibody that recognizes the molecule in paraffin-embedded tissue sections. A
      large series of B and T-cell lymphomas (679 cases) was studied, using tissue
      microarrays. RESULTS: Multiple myeloma, plasmacytoma and lymphoplasmacytic
      lymphoma cases (n=19) were positive. Plasmablastic lymphoma, oral mucosa-type
      (n=15), were also found to be positive. PRDM1 protein was expressed in some cases
      of B-cell neoplasia, i.e. chronic lymphocytic leukemia/small lymphocytic lymphoma
      (15%), diffuse large B-cell lymphoma (43%), classical Hodgkin's lymphoma (41%)
      and also in T-cell lymphoma (23%). INTERPRETATION AND CONCLUSIONS: Most B
      neoplastic cells showing plasmablastic differentiation were PRDM1-positive.
      Unexpectedly, a subset of diffuse large B-cell lymphoma expressed PRDM1, lacked
      detectable plasmablastic or immunoblastic changes and displayed more aggressive
      behavior, with a shorter failure-free survival. In contrast to normal B-cells,
      diffuse large B-cell lymphoma cases with increased PRDM1 expression co-expressed
      BCL-6 and MUM1/IRF4, confirming that PRDM1 expression in these tumors is
      insufficient to drive the full genetic program associated with plasmacytic
      differentiation.

PMID- 16585014
TI  - The predictive value of positron emission tomography scanning performed after two
      courses of standard therapy on treatment outcome in advanced stage Hodgkin's
      disease.
AB  - BACKGROUND AND OBJECTIVES: We explored the predictive value on therapy outcome of
      an early evaluation of treatment response by 18F-fluorodeoxyglucose position
      emission tomography (18F-FDG-PET) scan performed after two courses of
      conventional standard-dose chemotherapy in advanced-stage Hodgkin's disease.
      DESIGN AND METHODS: One hundred and eight patients with newly-diagnosed Hodgkin's
      disease in stage IIA with adverse prognostic factors, or in stage IIB through
      IVB, were re-staged with FDG-PET after two cycles of ABVD (PET-2). The end-point
      of the study was the predictive value of PET-2 on 2-year progression-free
      survival and 2-year failure-free survival. No treatment variation based only on
      PET-2 results was allowed. RESULTS: Eighty-eight patients attained complete
      remission (CR) while 20 showed disease progression during therapy or within 6
      months after having reached CR; one patient relapsed. PET-2 was positive in 20
      patients: 17 progressed during therapy, one relapsed and two remained in CR. By
      contrast, 85/88 (97%) patients with a negative PET-2 remained in CR; three
      progressed or relapsed early after the end of the chemotherapy. Thus, the
      positive predictive value of a PET-2 was 90% and the negative predictive value
      was 97%. The sensitivity, specificity and overall accuracy of PET-2 were 86%, 98%
      and 95%, respectively. The 2-year probability of failure-free survival for PET-2
      negative and for PET-2 positive patients was 96% and 6%, respectively (log rank
      test = 116.7, p < 0.01). INTERPRETATION AND CONCLUSIONS: 18F-FDG-PET scan
      performed after two courses of conventional standard-dose chemotherapy in
      advanced-stage Hodgkin's disease was able to predict treatment outcome in 103/108
      (95%) of the patients.

PMID- 16585015
TI  - Position emission tomography with or without computed tomography in the primary
      staging of Hodgkin's lymphoma.
AB  - BACKGROUND AND OBJECTIVES: In order to receive the most appropriate therapy,
      patients with Hodgkin's lymphoma (HL) must be accurately stratified into
      different prognostic staging groups. Computed tomography (CT) plays a pivotal
      role in the conventional staging. The aim of the present study was to investigate
      the value of positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose
      (FDG-PET) and combined FDG-PET/CT for the staging of HL patients, and the impact
      on the choice of treatment. DESIGN AND METHODS: Ninety-nine consecutive,
      prospectively included patients had FDG-PET and CT in their staging work-up.
      Sixty-one of the 99 patients had combined FDG-PET/CT. A standard of reference for
      each nodal region and organ was determined using all available information
      including scan results, histology and a minimum of one year's clinical follow-up
      data. The lack of a satisfactory diagnostic gold standard limits the reliability
      of accuracy calculations. RESULTS: FDG-PET would have upstaged 19% of patients
      and downstaged 5% of patients, leading to a different treatment in 9% of
      patients. For FDG-PET/CT, the corresponding figures are 17%, 5%, and 7%. In nodal
      regions, the sensitivity of FDG-PET and FDG-PET/CT seemed higher than that of CT
      (92% and 92% vs. 83%). FDG-PET identified more false positive nodal sites than
      did CT and FDG-PET/CT (1.6% vs 0.7% and 0.5%). FDG-PET and FDG-PET/CT were highly
      sensitive for evaluating organs (86% and 73%) while CT detected 37% of involved
      organs. INTERPRETATION AND CONCLUSIONS: FDG-PET and FDG-PET/CT have a substantial
      potential impact on staging and choice of treatment and the methods tend to
      upstage rather than downstage patients. FDG-PET and FDG-PET/CT seem to have a
      higher diagnostic accuracy than CT in the staging of HL. However, care should be
      taken so patients with an excellent prognosis and at risk of over-treatment do
      not receive more intensive treatment because of these staging methods.

PMID- 16585017
TI  - 18F-fluoro-deoxyglucose positron emission tomography for post-treatment
      evaluation of malignant lymphoma: a systematic review.
AB  - Despite the increasing number of publications concerning 18F-fluorodeoxyglucose
      positron emission tomography (FDG-PET) for post-treatment evaluation of lymphoma
      and the increasing availability of this novel diagnostic modality, its exact role
      in response assessment after therapy is still unknown. The aim of this study was
      to systematically review the literature regarding the diagnostic performance of
      dedicated FDG-PET in evaluation of first-line therapy of Hodgkin's disease and
      (aggressive) non-Hodgkin's lymphoma, and to calculate summary estimates of its
      sensitivity and specificity. The databases of PubMed and Embase were searched for
      relevant studies up to January 2004. Two reviewers independently assessed the
      methodological quality of each study. As a valid reference test, histology or
      follow-up of at least 12 months were accepted. A meta-analysis of the reported
      sensitivity and specificity of each study was performed. Fifteen studies,
      involving 705 patients, met the inclusion criteria. The studies had several
      design deficiencies. The majority of studies did not describe whether the
      reference test was interpreted without knowledge of the FDG-PET findings. In all
      studies, there was a description of the spectrum of patients included, i.e. all
      patients for post-treatment evaluation or only patients with substantial residual
      masses post-treatment. Pooled sensitivity and specificity for detection of
      residual disease in Hodgkin's lymphoma were 84% (95% CI 71-9192%) and 90% (95% CI
      84-9394%), respectively. For non-Hodgkin's lymphoma, pooled sensitivity and
      specificity were 72% (95% CI 61-82%), and 100% (95% CI 97-100%), respectively.
      FDG-PET showed reasonable sensitivity and high specificity for evaluation of
      first-line therapy in Hodgkin's and in non-Hodgkin's lymphoma. Standardization of
      procedures is required before implementation in clinical practice.

PMID- 16585018
TI  - Dose-finding study of high-dose simvastatin combined with standard chemotherapy
      in patients with relapsed or refractory myeloma or lymphoma.
AB  - In vitro statins induce apoptosis in myeloma and lymphoma cells in a dose-and
      time-dependent way. In combination with dexamethasone and doxorubicin, statins
      have a chemo-sensitizing effect. Twenty-eight patients with relapsed myeloma or
      lymphoma were treated with a dose-escalating regimen of simvastatin for 7 days
      followed by VAD in myeloma patients and CHOP in lymphoma patients. The maximum
      tolerated dose was 15 mg/kg/day simvastatin. The most frequently reported side
      effects were fatigue, gastrointestinal CTC grade 1-2 and neutropenic fever. The
      dose-limiting toxicity was neutropenic sepsis and grade 3 gastrointestinal side
      effects. High-dose simvastatin given immediately prior to chemotherapy is safe
      and tolerable up to a dose of 15 mg/kg/day.

PMID- 16585016
TI  - The natural history of hepatitis C virus infection in Italian patients with von
      Willebrand's disease: a cohort study.
AB  - BACKGROUND AND OBJECTIVES: Unlike patients with hemophilia, those with von
      Willebrand's disease (VWD) have a mild to moderate bleeding tendency requiring a
      lower rate of transfusion: moreover, the use of blood products in most Italian
      patients with VWD was greatly reduced following the introduction of desmopressin
      in 1977. The main objective of this study was to compare the prevalence and
      outcome of hepatitis C virus (HCV) infection in multi-transfused patients with
      VWD and in those with hemophilia A or B. DESIGN AND METHODS: In a large cohort of
      356 patients with VWD (41% type 1, 53% type 2 and 6% type 3) and 340 with
      hemophilia A (85%) or B (15%), all of whom were negative for human
      immunodeficiency virus (HIV) serum HCV markers, liver function tests and
      abdominal ultrasound were performed every 6 months for 6 years. RESULTS: VWD
      patients were less often transfused with any type of blood products than were
      hemophiliacs (40% versus 96%) and were, therefore, less frequently infected with
      HCV (39% versus 82%). HCV infection in patients with VWD occurred at an older
      mean age (22 versus 7 years), was of shorter duration (20 versus 31 years), and
      manifested less often with elevated transaminases (58% versus 83%). The risk of
      infection by HCV genotype 1a was significantly lower in patients with VWD than in
      hemophiliacs. Despite these differences in the features of HCV infection, the
      cumulative incidences of advanced liver disease (11% versus 10 %) and
      hepatocellular carcinoma (2% versus 4%) were very similar in the two groups of
      patients. INTERPRETATION AND CONCLUSIONS: VWD patients had lower prevalences of
      HCV infection with HCV and genotype 1a infections than did hemophiliacs,
      reflecting the different source and type of transfused blood products. HCV
      infection in both groups seems to run a relatively mild course, until now, but
      the high prevalence of genotypes resistant to curative antiviral therapies is of
      concern.

PMID- 16585019
TI  - Pegfilgrastim support for full delivery of BEACOPP-14 chemotherapy for patients
      with high-risk Hodgkin's lymphoma: results of a phase II study.
AB  - The primary endpoint of this feasibility study was to determine whether
      pegfilgrastim support could enable the delivery of the full dose of BEACOPP
      chemotherapy every 14 days on schedule. Forty-one patients with high-risk
      Hodgkin's lymphoma were randomized to receive pegfilgrastim (6 mg) on day 4 or 8
      of each cycle. Eighty-one percent of cycles administered were delivered at full
      dose and on schedule (FDOS). Response was retrospectively assessed in 27 patients
      at 6 months; 23 of these 27 patients (85%) achieved a complete response and one
      (4%) achieved a partial response. Toxicities were mostly moderate in intensity.
      These results support the feasibility of delivering full dose, on schedule
      BEACOPP-14, chemotherapy with pegfilgrastim support.

PMID- 16585020
TI  - A double-blind low dose-finding phase II study of granulocyte colony-stimulating
      factor combined with chemotherapy for stem cell mobilization in patients with non
      Hodgkin's lymphoma.
AB  - The aim of the study was to define the minimal effective dose (MED) of
      granulocyte colony-stimulating factor (G-CSF) among five daily doses following
      chemotherapy for peripheral blood stem cell (PBSC) collection. Twenty-five
      patients were included in this double-blind dose-finding phase II study conducted
      according to a two-stage Bayesian design. The estimated probabilities of success
      for PBSC collection for the G-CSF doses of 50, 75, 100, 125 and 150 microg/m2/day
      were 84%, 87.7%, 91%, 93.9 and 96.4%, respectively. Low G-CSF doses may be used
      with a similar probability of success as conventional doses and could allow
      significant savings.

PMID- 16585021
TI  - High prevalence of hepatitis B virus infection in B-cell non-Hodgkin's lymphoma.
AB  - In this hospital-based, multicenter case-control study we investigated the
      prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus
      (HCV) co-infection among B-cell non-Hodgkin's lymphoma (B-NHL) cases and
      controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other
      departments of the same hospitals were studied. The prevalence of positivity for
      hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among
      controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV
      co-infection was found in four cases, but in no controls. The finding of a
      positive association between HBV infection and B-NHL raises the possibility that
      HBV may play an etiologic role in the induction of B-NHL.

PMID- 16585022
TI  - Immune tolerance induction with recombinant factor VIII in hemophilia A patients
      with high responding inhibitors.
AB  - Immune tolerance induction (ITI) eradicates inhibitors in patients with
      hemophilia A. This study was designed to investigate the success rate of ITI in
      high-responding inhibitor patients with severe hemophilia A using recombinant
      factor VIII (rFVIII). Twenty-six patients received different ITI regimens until a
      normal recovery (>66%) and half-life (>6 h) of infused FVIII was achieved. In
      order to maximize the chance of success, the initiation of ITI was deferred in
      the majority of patients until the inhibitor declined to <10 BU. Twenty-two
      patients (85%) had baseline inhibitor levels <10 BU (median 2.3 BU) when ITI
      began. Within a median of 6 months, immune tolerance was achieved in 19 of 26
      patients (73%) including 12/17 (70%) with intron 22 inversion, 5/7 (71%) with
      other null mutations and two with small deletion/insertions in the F8 gene. In
      conclusion, recombinant FVIII induces a high rate of immune tolerance even in
      carriers of null F8 mutations.

PMID- 16585023
TI  - Lipoprotein (a) in young individuals as a marker of the presence of ischemic
      heart disease and the severity of coronary lesions.
AB  - The purpose of this study was to evaluate whether high levels and small isoforms
      of lipoprotein (a) [Lp(a)] are markers of risk of early myocardial infarction and
      markers of the severity of coronary atherosclerosis. Lp(a) levels and small
      apo(a) isoforms were higher in 222 patients than in 199 controls (p<0.001). In
      patients, Lp(a)> or =30 mg/dL was associated with the presence of coronary
      lesions (p=0.007) and the severity of coronary atherosclerosis (p=0.002). The
      present study suggests that Lp(a) levels and small isoforms are markers of early
      myocardial infarction and that Lp(a) levels > or =30 mg/dL are associated with
      severe patterns of coronary atherosclerosis.

PMID- 16585024
TI  - Expression of the putatively regulatory T-cell marker FOXP3 by CD4(+)CD25+ T
      cells after pediatric hematopoietic stem cell transplantation.
AB  - FOXP3 has been proposed to be critical for the regulatory function of CD4(+)CD25+
      T cells and it has been reported that its expression correlates with protection
      from graft-versus-host-disease (GvHD) after allogeneic hematopoietic stem cell
      transplantation (HSCT). Here, by monitoring 28 pediatric HSCT recipients, we
      found that the levels of FOXP3-mRNA expression in highly enriched CD4(+)CD25+
      cells were identical to those in healthy controls irrespective of GvHD status.
      Moreover, FOXP3-mRNA was abundant in recently in vitro stimulated CD4(+)CD25+
      cells that lacked regulatory function. Together these findings suggest that FOXP3
      mRNA expression primarily reflects CD4(+)CD25+ cell frequency rather than
      defining the regulatory potential of CD4(+)CD25+ T cells and GvHD risk after
      HSCT.

PMID- 16585025
TI  - A case analysis of INFOMED: the Cuban national health care telecommunications
      network and portal.
AB  - BACKGROUND: The Internet and telecommunications technologies contribute to
      national health care system infrastructures and extend global health care
      services markets. The Cuban national health care system offers a model to show
      how a national information portal can contribute to system integration, including
      research, education, and service delivery as well as international trade in
      products and services. OBJECTIVE: The objectives of this paper are (1) to present
      the context of the Cuban national health care system since the revolution in
      1959, (2) to identify virtual institutional infrastructures of the system
      associated with the Cuban National Health Care Telecommunications Network and
      Portal (INFOMED), and (3) to show how they contribute to Cuban trade in
      international health care service markets. METHODS: Qualitative case research
      methods were used to identify the integrated virtual infrastructure of INFOMED
      and to show how it reflects socialist ideology. Virtual institutional
      infrastructures include electronic medical and information services and the
      structure of national networks linking such services. RESULTS: Analysis of
      INFOMED infrastructures shows integration of health care information, research,
      and education as well as the interface between Cuban national information
      networks and the global Internet. System control mechanisms include horizontal
      integration and coordination through virtual institutions linked through INFOMED,
      and vertical control through the Ministry of Public Health and the government
      hierarchy. Telecommunications technology serves as a foundation for a dual market
      structure differentiating domestic services from international trade.
      CONCLUSIONS: INFOMED is a model of interest for integrating health care
      information, research, education, and services. The virtual infrastructures
      linked through INFOMED support the diffusion of Cuban health care products and
      services in global markets. Transferability of this model is contingent upon
      ideology and interpretation of values such as individual intellectual property
      and confidentiality of individual health information. Future research should
      focus on examination of these issues and their consequences for global markets in
      health care.

PMID- 16585026
TI  - Physicians' use of email with patients: factors influencing electronic
      communication and adherence to best practices.
AB  - BACKGROUND: With the public's increased use of the Internet, the use of email as
      a means of communication between patients and physicians will likely increase.
      Yet, despite evidence of increased interest by patients, e-mail use by physicians
      for clinical care has been slow. OBJECTIVE: To examine the factors associated
      with physician-patient e-mail, and report on the physicians' adherence to
      recognized guidelines for e-mail communication. METHODS: Cross-sectional survey
      (March-May, 2005) of all primary care physicians (n = 10253), and a 25%
      stratified, random sample of all ambulatory clinical specialists (n = 3954) in
      the state of Florida. Physicians were surveyed on email use with patients,
      adherence to recognized guidelines, and demographics. RESULTS: The 4203
      physicians completed the questionnaire (a 28.2% participation rate). Of these,
      689 (16.6%) had personally used e-mail to communicate with patients. Only 120
      (2.9%) used e-mail with patients frequently. In univariate analysis, e-mail use
      correlated with physician age (decreased use: age > 61; P = .014), race
      (decreased use: Asian background; P < .001), medical training (increased use:
      family medicine, P = .001; or surgical specialty, P = .007; but not internal
      medicine, P = .112), practice size (> 50 physicians, P < .001), and geographic
      location (urban 17.2% vs. rural, 7.9%; P < .001). Multivariate modeling showed
      that only practice size greater than 50 (OR = 1.94; 95% CI = 1.01-3.79) and Asian
      American race (OR = 0.26; 95% CI = 0.14-0.49) were related to e-mail use with
      patients. Remarkably, only 46 physicians (6.7%) adhered to at least half of the
      13 selected guidelines for e-mail communication. CONCLUSIONS: This large survey
      of physicians, practicing in ambulatory settings, shows only modest advances in
      the adoption of e-mail communication, and little adherence to recognized
      guidelines for e-mail correspondence. Further efforts are required to educate
      both patients and physicians on the advantages and limitations of e-mail
      communication, and to remove fiscal and legal barriers to its adoption.

PMID- 16585028
TI  - Using sequential e-mail messages to promote health behaviors: evidence of
      feasibility and reach in a worksite sample.
AB  - BACKGROUND: US adults report suboptimal physical activity and fruit and vegetable
      intake. Innovative strategies to promote healthy behaviors are needed. Employee
      health promotion programs have been associated with reductions in health risks
      but are labor-intensive and costly to implement. E-mail and Web-based worksite
      programs have the potential to reach a broad adult population and to provide a
      cost-effective approach to employee wellness programming. OBJECTIVE: To assess
      the feasibility of using sequential e-mail messages to promote physical activity
      and increase fruit and vegetable intake among employed adults. METHODS: Employees
      at one worksite of a large insurance company in New York State were invited to
      participate. Interested workers provided written consent. After completing a
      baseline survey, participants received daily e-mails, Monday through Friday, for
      26 weeks. The e-mails provided (a) succinct strategies to encourage physical
      activity or increase fruit and vegetable intake and (b) links to detailed Web
      based information and tools. Program reach was assessed by the number of e-mails
      opened, measures of sustained participation over 6 months, and the number of
      health-related Web-links clicked. RESULTS: Of 960 employees, 388 (40%) consented
      to participate; of these, 345 (89%) completed the baseline health survey. After 6
      months, 70% of the 345 participants had opened 50% or more of the daily e-mails.
      In addition, 75% of participants continued to open at least one e-mail a week
      through week 26 of the study. E-mail opening rates did not vary by gender, age,
      income, education, ethnicity, or baseline health behavior. CONCLUSIONS: The rate
      of enrollment and sustained participation document the feasibility, broad reach,
      employee acceptance, and potential value of using electronic communications for
      health promotion in the workplace.

PMID- 16585029
TI  - What is eHealth (6): perspectives on the evolution of eHealth research.
AB  - BACKGROUND: The field of eHealth holds promise for supporting and enabling health
      behavior change and the prevention and management of chronic disease. OBJECTIVE:
      In order to establish areas of congruence and controversy among contributors to
      the early development, evaluation, and dissemination of eHealth applications, as
      well as the desire to inform an evaluation research funding agenda, 38
      semistructured, qualitative interviews were conducted among stakeholders in
      eHealth between May 2002 and September 2003. METHODS: Participants were asked
      about their perspectives on the credibility, value, and future potential of
      information technology for health behavior change and chronic disease management.
      Interviews were coded and analyzed for emergent themes using qualitative methods.
      RESULTS: Consistent themes were identified across stakeholder groups, with slight
      differences in emphasis. These topics included the following: (1) consensus and
      standardization-most stakeholders expressed a strong desire for a more
      coordinated, rigorous effort to define and integrate the field; (2) evaluation
      methods and challenges-demonstrating outcomes is required to establish eHealth
      quality and efficacy, but stakeholders were not satisfied with the sensitivity,
      validity, and reliability of existing outcome measures; (3) quality, value, and
      future potential-the intersection between eHealth's potential cost-effectiveness,
      efficiency, and improved clinical status among users generated a high degree of
      interest; and (4) health disparities-many stakeholders contended that
      traditionally underserved populations will particularly benefit from eHealth
      applications, although others argued that the underserved are also disadvantaged
      in terms of access to technology. CONCLUSIONS: Recommendations included the need
      for improvement and formalization of development and evaluation standards across
      private and public sectors, additional research on the technology needs and
      preferences of traditionally underserved populations, and long-term epidemiologic
      studies of the impact of eHealth on outcomes and cost-effectiveness.

PMID- 16585030
TI  - Influences of canopy photosynthesis and summer rain pulses on root dynamics and
      soil respiration in a young ponderosa pine forest.
AB  - Our first objective was to link the seasonality of fine root dynamics with soil
      respiration in a ponderosa pine (Pinus ponderosa P. & C. Lawson) plantation
      located in the Sierra Nevada of California. The second objective was to examine
      how canopy photosynthesis influences fine root initiation, growth and mortality
      in this ecosystem. We compared CO2 flux measurements with aboveground and
      belowground root dynamics. Initiation of fine root growth coincided with tree
      stem thickening and shoot elongation, preceding new needle growth. In the spring,
      root, shoot and stem growth occurred simultaneously with the increase in canopy
      photosynthesis. Compared with the other tree components, initial growth rate of
      fine roots was the highest and their growing period was the shortest. Both above
      and belowground components completed 90% of their growth by the end of July and
      the growing season lasted approximately 80 days. The period for optimal growth is
      short at the study site because of low soil temperatures during winter and low
      soil water content during summer. High photosynthetic rates were observed
      following unusual late-summer rains, but tree growth did not resume. The
      autotrophic contribution to soil respiration was 49% over the whole season, with
      daily contributions ranging between 18 and 87%. Increases in soil and ecosystem
      respiration were observed during spring growth; however, the largest variation in
      soil respiration occurred during summer rain events when no growth was observed.
      Both the magnitude and persistence of the soil respiration pulses were positively
      correlated with the amount of rain. These pulses accounted for 16.5% of soil
      respiration between Days 130 and 329.

PMID- 16585031
TI  - A comparative analysis of simulated and observed photosynthetic CO2 uptake in two
      coniferous forest canopies.
AB  - Gross canopy photosynthesis (P(g)) can be simulated with canopy models or
      retrieved from turbulent carbon dioxide (CO2) flux measurements above the forest
      canopy. We compare the two estimates and illustrate our findings with two case
      studies. We used the three-dimensional canopy model MAESTRA to simulate P(g) of
      two spruce forests differing in age and structure. Model parameter acquisition
      and model sensitivity to selected model parameters are described, and modeled
      results are compared with independent flux estimates. Despite higher photon
      fluxes at the site, an older German Norway spruce (Picea abies L. (Karst.))
      canopy took up 25% less CO2 from the atmosphere than a young Scottish Sitka
      spruce (Picea sitchensis (Bong.) Carr.) plantation. The average magnitudes of
      P(g) and the differences between the two canopies were satisfactorily represented
      by the model. The main reasons for the different uptake rates were a slightly
      smaller quantum yield and lower absorptance of the Norway spruce stand because of
      a more clumped canopy structure. The model did not represent the scatter in the
      turbulent CO2 flux densities, which was of the same order of magnitude as the non
      photosynthetically-active-radiation-induced biophysical variability in the
      simulated P(g). Analysis of residuals identified only small systematic
      differences between the modeled flux estimates and turbulent flux measurements at
      high vapor pressure saturation deficits. The merits and limitations of
      comparative analysis for quality evaluation of both methods are discussed. From
      this analysis, we recommend use of both parameter sets and model structure as a
      basis for future applications and model development.

PMID- 16585032
TI  - Changes in photosynthesis and leaf characteristics with tree height in five
      dipterocarp species in a tropical rain forest.
AB  - Variations in leaf photosynthetic, morphological and biochemical properties with
      increasing plant height from seedlings to emergent trees were investigated in
      five dipterocarp species in a Malaysian tropical rain forest. Canopy openness
      increased significantly with tree height. Photosynthetic properties, such as
      photosynthetic capacity at light saturation, light compensation point, maximum
      rate of carboxylation and maximum rate of photosynthetic electron transport, all
      increased significantly with tree height. Leaf morphological and biochemical
      traits, such as leaf mass per area, palisade layer thickness, nitrogen
      concentration per unit area, chlorophyll concentration per unit dry mass and
      chlorophyll to nitrogen ratio, also changed significantly with tree height. Leaf
      properties had simple and significant relationships with tree height, with few
      intra- and interspecies differences. Our results therefore suggest that the
      photosynthetic capacity of dipterocarp trees depends on tree height, and that the
      trees adapt to the light environment by adjusting their leaf morphological and
      biochemical properties. These results should aid in developing models that can
      accurately estimate carbon dioxide flux and biomass production in tropical rain
      forests.

PMID- 16585033
TI  - Responses of Picea mariana to elevated CO2 concentration during growth, cold
      hardening and dehardening: phenology, cold tolerance, photosynthesis and growth.
AB  - Seedlings from a northern and a southern provenance of black spruce (Picea
      mariana Mill. BSP) from eastern Canada were exposed to 37 or 71 Pa of carbon
      dioxide (CO2) during growth, cold hardening and dehardening in a greenhouse. Bud
      phenology, cold tolerance and photosynthetic efficiency were assessed during the
      growing and over-wintering periods. Bud set occurred earlier in elevated [CO2]
      than in ambient [CO2], but it was later in the southern provenance than in the
      northern provenance. An increase in seedling cold tolerance in early fall was
      related to early bud set in elevated [CO2]. Maximal photosystem II (PSII)
      photochemical efficiency (F(v)/F(m)), effective quantum yield (phi(PSII)),
      photochemical quenching (q(P)), light-saturated photosynthesis (Amax), apparent
      quantum efficiency (alpha'), light-saturated rate of carboxylation (Vcmax) and
      electron transport (Jmax) decreased during hardening and recovered during
      dehardening. Although Amax and alpha' were higher in elevated [CO2] when measured
      at the growth [CO2], down-regulation of photosynthesis occurred in elevated [CO2]
      as shown by lower F(v)/F(m), phi(PSII), Vcmax and Jmax. Elevated [CO2] reduced
      gene expression of the small subunit of Rubisco and also decreased chlorophyll
      a/chlorophyll b ratio and nitrogen concentration in needles, confirming our
      observation of down-regulation of photosynthesis. Elevated [CO2] increased the
      CO2 diffusion gradient and decreased photorespiration, which may have contributed
      to enhance Amax despite down-regulation of photosynthesis. Total seedling dry
      mass was higher in elevated [CO2] than in ambient [CO2] at the end of the growing
      season. However, because of earlier bud formation and cold hardening, and down
      regulation of photosynthesis during fall and winter in elevated [CO2], the
      treatment difference in dry mass increment was less by the end of the winter than
      during the growing season. Differences in photosynthetic rate observed during
      fall, winter and spring account for the inter-annual variations in carbon
      assimilation of black spruce seedlings: our results demonstrate that these
      variations need to be considered in carbon budget studies.

PMID- 16585034
TI  - Climate warming and the risk of frost damage to boreal forest trees:
      identification of critical ecophysiological traits.
AB  - According to a hypothesis presented in the mid-1980s, climate warming will,
      paradoxically, increase the risk of frost damage to trees in the boreal and
      temperate zones. Dehardening and even growth onset may occur in trees during mild
      spells in winter and early spring, resulting in damage during subsequent periods
      of frost. In the present study, ecophysiological traits critical to the
      occurrence of frost damage in trees in the boreal zone were identified.
      Diagnostic computer simulations were performed to examine why one simulation
      model of frost hardiness in an earlier study predicted heavy frost damage as a
      consequence of climate warming, whereas another closely related model did not.
      The modeling comparison revealed that the response of ontogenetic development to
      air temperature during quiescence is a critical factor determining the risk of
      frost damage. As the response can be readily determined in growth-chamber
      experiments, the findings of the present study can be used to guide experimental
      work on the environmental regulation of the annual cycle of frost hardiness in
      trees.

PMID- 16585035
TI  - Interspecific variation in vessel size, growth and drought tolerance of broad
      leaved trees in semi-arid regions of Kenya.
AB  - In semi-arid regions, trees often wither during the dry season. Withering is
      sometimes manifest as die-back, whereby whithering results in shoot death, which
      progresses downward from the uppermost part of the crown. In this study, we
      measured the relationships between height growth and diameter at breast height,
      die-back frequency and severity, vessel size and specific hydraulic conductivity
      of four evergreen (Senna siamea (Lamk) H.S. Irwin & Barneby, Jacaranda
      mimosifolia D. Don, Azadirachta indica A.H.L. Juss and Acacia gerrardii Benth.)
      and one deciduous (Melia volkensii Gurke) plantation tree species in Kenya, which
      has a conspicuous dry season. Die-back occurred readily in some species, but not
      in others. Senna siamea showed the highest specific hydraulic conductivity and
      the highest growth rate among the five species and was quite susceptible to die
      back. Among species, height growth and specific hydraulic conductivity were
      positively correlated with vessel size and negatively correlated with die-back
      frequency, suggesting a trade-off between growth rate and drought tolerance. This
      implies that an adaptation to rapid growth under humid conditions leads to low
      drought tolerance. However, the deciduous tree Melia volkensii showed high
      specific hydraulic conductivity and growth, with no symptoms of die-back,
      implying that a mechanism associated with the deciduous habit results in drought
      avoidance by reducing the requirement for water during the dry season.

PMID- 16585036
TI  - Terminal bud failure of black cottonwood (Populus trichocarpa) exposed to salt
      laden winter storms.
AB  - At coastal sites, trees are exposed to marine aerosols that may cause foliar
      necrosis and shoot dieback, which can result in deformed crowns and contorted
      stems. A six-year study of leaf primordia in terminal buds of black cottonwood
      trees (Populus trichocarpa Torr. & Gray) on Heimaey Island off the south coast of
      Iceland was undertaken to elucidate the physiological events associated with salt
      deposition-related bud failure. Leaf and bud lengths, dry mass, water content and
      chloride concentrations were monitored and related to four phenological stages:
      (1) bud set; (2) dormancy induction; (3) dormancy release; and (4) bud break. The
      trees set buds in July and shed their leaves by late September. Leaf primordia
      generally stopped growing by September 10 +/- 22 days and attained midwinter
      water content in late September. Leaf growth commenced in the terminal buds by
      March 2 +/- 16 days, but mean dates of bud swelling and bud break were April 29
      +/- 19 and May 10 +/- 12 days. In summer and until November, chloride
      concentrations in leaf primordia were low, but increasing. Chloride
      concentrations remained stable from December to February, even though the dormant
      trees were exposed to large amounts of marine aerosols. In February and March,
      three events occurred more or less simultaneously: (1) leaf extension growth
      commenced; (2) chloride concentration surged in the leaf primordia; and (3) the
      leaf primordia began to hydrate. Following dormancy release, growth and hydration
      of leaf primordia were negatively related to chloride concentration in the leaf
      primordia, with inhibition of leaf growth, tissue hydration and chloride
      acquisition occurring at a chloride concentration threshold estimated at 7.3 mg
      Cl- g(-1) tissue water. Necrosis of leaf primordia was observed above 14 mg Cl-
      g(-1) tissue water. Growth and hydration of leaves at bud break in mid-May was
      explained by a three-parameter logistic model of chloride concentration in leaf
      primordia at the end of March. By mid-May, 90% of all buds remained non-necrotic,
      but only 56% the terminal buds had broken. Salt alone explained the observed
      growth suppression of leaf primordia in the buds and the resultant failure of
      terminal buds to break by mid-May.

PMID- 16585037
TI  - Dark respiration rate increases with plant size in saplings of three temperate
      tree species despite decreasing tissue nitrogen and nonstructural carbohydrates.
AB  - In shaded environments, minimizing dark respiration during growth could be an
      important aspect of maintaining a positive whole-plant net carbon balance.
      Changes with plant size in both biomass distribution to different tissue types
      and mass-specific respiration rates (R(d)) of those tissues would have an impact
      on whole-plant respiration. In this paper, we evaluated size-related variation in
      R(d), biomass distribution, and nitrogen (N) and total nonstructural carbohydrate
      (TNC) concentrations of leaves, stems and roots of three cold-temperate tree
      species (Abies balsamea (L.) Mill, Acer rubrum L. and Pinus strobus L.) in a
      forest understory. We sampled individuals varying in age (6 to 24 years old) and
      in size (from 2 to 500 g dry mass), and growing across a range of irradiances
      (from 1 to 13% of full sun) in northern Minnesota, USA. Within each species, we
      found small changes in R(d), N and TNC when comparing plants growing across this
      range of light availability. Consistent with our hypotheses, as plants grew
      larger, whole-plant N and TNC concentrations in all species declined as a result
      of a combination of changes in tissue N and shifts in biomass distribution
      patterns. However, contrary to our hypotheses, whole-plant and tissue R(d)
      increased with plant size in the three species.

PMID- 16585038
TI  - In vivo and in situ rhizosphere respiration in Acer saccharum and Betula
      alleghaniensis seedlings grown in contrasting light regimes.
AB  - A perfusive method combined with an open-system carbon dioxide measurement system
      was used to assess rhizosphere respiration of Acer saccharum Marsh. (sugar maple)
      and Betula alleghaniensis Britton (yellow birch) seedlings grown in 8-l pots
      filled with coarse sand. We compared in vivo and in situ rhizosphere respiration
      between species, among light regimes (40, 17 and 6% of full daylight) and at
      different times during the day. To compute specific rhizosphere respiration,
      temperature corrections were made with either species-specific coefficients (Q10)
      based on the observed change in respiration rate between 15 and 21 degrees C or
      an arbitrarily assigned Q10 of 2. Estimated, species-specific Q10 values were 3.0
      and 3.4 for A. saccharum and B. alleghaniensis, respectively, and did not vary
      with light regime. Using either method of temperature correction, specific
      rhizosphere respiration did not differ either between A. saccharum and B.
      alleghaniensis, or among light regimes except in A. saccharum at 6% of full
      daylight. At this irradiance, seedlings were smaller than in the other light
      treatments, with a larger fine root fraction of total root dry mass, resulting in
      higher respiration rates. Specific rhizosphere respiration was significantly
      higher during the afternoon than at other times of day when temperature-corrected
      on the basis of an arbitrary Q10 of 2, suggesting the possibility of diurnal
      variation in a temperature-independent component of rhizosphere respiration.

PMID- 16585039
TI  - Plasticity of growth and sylleptic branchiness in two poplar families grown at
      three sites across Europe.
AB  - Two hybrid poplar maternal half-sib families, resulting from controlled crosses
      of the female parent Populus deltoides 'S9-2' with P. nigra 'Ghoy' and P.
      trichocarpa 'V24', were grown at three sites: northern Italy, central France and
      southern England. Juvenile stem growth traits (height, circumference and volume)
      and sylleptic branchiness (number of branches, density of branches per unit of
      stem height, percentage of the stem carrying branches and distance of the highest
      sylleptic branch to the top of the stem) were measured on 1-year-old shoots. Our
      general objectives were to determine the degree to which the expression of stem
      growth and syllepsis and the relationships between them are affected by
      environmental conditions and to evaluate the efficiency of indirect selection for
      stem growth using branching traits as secondary criteria. The performance of both
      families differed significantly within and between sites. Pronounced heterosis
      was observed and highly significant genotype x environment interactions were
      found for all traits across the sites. Syllepsis showed more marked genetic
      variation and plasticity than stem growth traits. Relationships between sylleptic
      branchiness and stem growth depended on environmental conditions. Heritability
      values at the individual level ranged between 0.09 and 0.59, but genetic gain in
      stem volume was not significantly improved when selection was based on sylleptic
      branch characteristics. However, despite strong phenotypic plasticity among
      sites, genotypic ranking among the sites was relatively stable.

PMID- 16585040
TI  - Differential light responses of Mediterranean tree saplings: linking
      ecophysiology with regeneration niche in four co-occurring species.
AB  - The ecophysiological mechanisms underlying plant-plant interactions and forest
      regeneration processes in Mediterranean ecosystems are poorly understood, and the
      experimental evidence for the role of light availability in these processes is
      particularly scant. We analyzed the effects of high and low irradiances on 31
      ecological, morphological and physiological variables in saplings of four late
      successional Mediterranean trees, two deciduous (Acer opalus subsp. granatense
      (Boiss.) Font Quer & Rothm. and Quercus pyrenaica Willd.) and two evergreen
      (Pinus nigra Arnold subsp. salzmannii (Dunal) Franco and Quercus ilex L.), which
      coexist in mature montane forests. Species differed in both their capacity to
      withstand high radiation and in their shade tolerance. The two deciduous species
      were the least tolerant to high radiation, exhibiting both dynamic and chronic
      photoinhibition in full sunlight, with severe implications for gas exchange and
      photosynthetic performance. Excess light severely limited the survival of A.
      opalus subsp. granatense, even minor reductions of excessive radiation (from full
      sunlight to 80% sunlight) being crucial for sapling survival. Among species, P.
      nigra was the most tolerant of high irradiances but showed the poorest shade
      acclimation. Interspecific differences in the mechanisms of response to light
      provide a partial explanation of the differential regeneration patterns
      previously reported for these species, with shade-tolerant plants (i.e.,
      deciduous broadleaf species) benefiting the most from associations with nurse
      plants. We conclude that light availability is an important environmental factor
      defining the regeneration niche of Mediterranean woody species.

PMID- 16585041
TI  - Leaf gas exchange characteristics of three neotropical mangrove species in
      response to varying hydroperiod.
AB  - We determined how different hydroperiods affected leaf gas exchange
      characteristics of greenhouse-grown seedlings (2002) and saplings (2003) of the
      mangrove species Avicennia germinans (L.) Stearn., Laguncularia racemosa (L.)
      Gaertn. f., and Rhizophora mangle L. Hydroperiod treatments included no flooding
      (unflooded), intermittent flooding (intermittent), and permanent flooding
      (flooded). Plants in the intermittent treatment were measured under both flooded
      and drained states and compared separately. In the greenhouse study, plants of
      all species maintained different leaf areas in the contrasting hydroperiods
      during both years. Assimilation-light response curves indicated that the
      different hydroperiods had little effect on leaf gas exchange characteristics in
      either seedlings or saplings. However, short-term intermittent flooding for
      between 6 and 22 days caused a 20% reduction in maximum leaf-level carbon
      assimilation rate, a 51% lower light requirement to attain 50% of maximum
      assimilation, and a 38% higher demand from dark respiration. Although
      interspecific differences were evident for nearly all measured parameters in both
      years, there was little consistency in ranking of the interspecific responses.
      Species by hydroperiod interactions were significant only for sapling leaf area.
      In a field study, R. mangle saplings along the Shark River in the Everglades
      National Park either demonstrated no significant effect or slight enhancement of
      carbon assimilation and water-use efficiency while flooded. We obtained little
      evidence that contrasting hydroperiods affect leaf gas exchange characteristics
      of mangrove seedlings or saplings over long time intervals; however, intermittent
      flooding may cause short-term depressions in leaf gas exchange. The resilience of
      mangrove systems to flooding, as demonstrated in the permanently flooded
      treatments, will likely promote photosynthetic and morphological adjustment to
      slight hydroperiod shifts in many settings.

PMID- 16585042
TI  - In vitro regeneration of Salix nigra from adventitious shoots.
AB  - Black willow (Salix nigra Marsh.) is the largest and only commercially important
      willow species in North America. It is a candidate for phytoremediation of
      polluted soils because it is fast-growing and thrives on floodplains throughout
      eastern USA. Our objective was to develop a protocol for the in vitro
      regeneration of black willow plants that could serve as target material for gene
      transformation. Unexpanded inflorescence explants were excised from dormant buds
      collected from three source trees and cultured on woody plant medium (WPM)
      supplemented with one of: (1) 0.1 mg l(-1) thidiazuron (TDZ); (2) 0.5 mg l(-1) 6
      benzoaminopurine (BAP); or (3) 1 mg l(-1) BAP. All plant growth regulator (PGR)
      treatments induced direct adventitious bud formation from the genotypes. The
      percentage of explants producing buds ranged from 20 to 92%, depending on
      genotype and treatment. Although most of the TDZ-treated inflorescences produced
      buds, these buds failed to elongate into shoots. Buds on explants treated with
      BAP elongated into shoots that were easily rooted in vitro and further
      established in potting mix in high humidity. The PGR treatments significantly
      affected shoot regeneration frequency (P < 0.01). The highest shoot regeneration
      frequency (36%) was achieved with Genotype 3 cultured on 0.5 mg l(-1) BAP. Mean
      number of shoots per explant varied from one to five. The ability of black willow
      inflorescences to produce adventitious shoots makes them potential targets for
      Agrobacterium-mediated transformation with heavy-metal-resistant genes for
      phytoremediation.

PMID- 16585044
TI  - Practice parameter: evaluation and treatment of depression, psychosis, and
      dementia in Parkinson disease (an evidence-based review): report of the Quality
      Standards Subcommittee of the American Academy of Neurology.

PMID- 16585048
TI  - Synthesis and structures of iron nanoparticles coated with boron nitride
      nanomaterials.
AB  - Iron (Fe) nanoparticles coated with boron nitride (BN) nanomaterials were
      synthesized by using Fe(4)N and B powders as raw materials. The Fe(4)N was
      reduced to alpha-Fe during annealing at 1000 degrees C for several hours with
      flowing 100 sccm N(2) gas. The reaction was predicted by Ellingham diagram. The
      atomic structure and magnetic properties were investigated by high-resolution
      electron microscopy and vibrating sample magnetometer system.

PMID- 16585049
TI  - Effects of armed conflict on access to emergency health care in Palestinian West
      Bank: systematic collection of data in emergency departments.
AB  - OBJECTIVE: To assess the impact of restrictions in access to hospital services
      imposed on the civilian population during the armed conflict in the Palestinian
      territories occupied by Israel. DESIGN: Consecutive registration of demographic
      and medical data, with information about transportation time, delay in access to
      hospital, and course of hospital contact. SETTING: Three hospital emergency
      departments in Bethlehem and Nablus, in the occupied Palestinian West Bank,
      during one week in each hospital. PARTICIPANTS: All patients seeking health care
      in the three hospitals during the study period. RESULTS: A total of 394 of the
      2228 emergency department contacts reported being delayed at checkpoints or by
      detours on their way to the emergency department. Hospital admission was
      significantly more common for these patients: 32% (n = 125) compared with 13% (n
      = 205) among those who were not delayed. CONCLUSION: 18% of the emergency
      department contacts were delayed because of the occupation. The higher hospital
      admission rate in this group suggests that restrictions in access to hospital
      services influence the severity of the medical conditions presented.

PMID- 16585051
TI  - Characterization of the muscle involvement in dynamin 2-related centronuclear
      myopathy.
AB  - Centronuclear myopathy (CNM) is a slowly progressive congenital myopathy
      characterized by abnormal centrally located nuclei in a large number of muscle
      fibres. Recently, different missense mutations affecting the middle domain of the
      dynamin 2 (DNM2) have been shown to cause autosomal dominant CNM. In order to
      better define the phenotype of DNM2-related CNM, we report here on the clinical
      and muscle imaging findings of 10 patients harbouring DNM2 mutations. DNM2-CNM is
      characterized by slowly progressive muscular weakness usually beginning in
      adolescence or early adulthood. In addition to bilateral ptosis, our data show
      that distal muscle weakness often exceeds proximal involvement. Furthermore,
      electrophysiological investigations frequently demonstrated signs of mild axonal
      peripheral nerve involvement, and electromyographical examination may show
      neuropathic changes in addition to the predominant myopathic changes. These
      features overlap with findings seen in the phenotype of DNM2-related autosomal
      dominant Charcot-Marie-Tooth disease type 2B. In all 10 DNM2-CNM patients, muscle
      computer tomography assessment showed a consistent pattern of muscular
      involvement and a characteristic temporal course with early and predominant
      distal muscle involvement, and later affection of the posterior thigh compartment
      and gluteus minimus muscles. The recognition of this specific imaging pattern of
      muscle involvement--distinct to the reported patterns in other congenital
      myopathies--may enable a better selection for direct genetic testing.

PMID- 16585050
TI  - Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients:
      meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: To evaluate the clinical benefit of lipid lowering drug treatment in
      patients with and without diabetes mellitus, for primary and secondary
      prevention. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane,
      Medline, Embase, and reference lists up to April 2004. STUDY SELECTION:
      Randomised, placebo controlled, double blind trials with a follow-up of at least
      three years that evaluated lipid lowering drug treatment in patients with and
      without diabetes mellitus. DATA EXTRACTION: Two independent reviewers extracted
      data. The primary outcome was major coronary events defined as coronary heart
      disease death, non-fatal myocardial infarction, or myocardial revascularisation
      procedures. RESULTS: Twelve studies were included. Lipid lowering drug treatment
      was found to be at least as effective in diabetic patients as in non-diabetic
      patients. In primary prevention, the risk reduction for major coronary events was
      21% (95% confidence interval 11% to 30%; P < 0.0001) in diabetic patients and 23%
      (12% to 33%; P = 0.0003) in non-diabetic patients. In secondary prevention, the
      corresponding risk reductions were 21% (10% to 31%; P = 0.0005) and 23% (19% to
      26%; P < or = 0.00001). However, the absolute risk difference was three times
      higher in secondary prevention. When results were adjusted for baseline risk,
      diabetic patients benefited more in both primary and secondary prevention. Blood
      lipids were reduced to a similar degree in both groups. CONCLUSIONS: The evidence
      that lipid lowering drug treatment (especially statins) significantly reduce
      cardiovascular risk in diabetic and non-diabetic patients is strong and suggests
      that diabetic patients benefit more, in both primary and secondary prevention.
      Future research should define the threshold for treatment of these patients and
      the desired target lipid concentrations, especially for primary prevention.

PMID- 16585052
TI  - Lost in semantic space: a multi-modal, non-verbal assessment of feature knowledge
      in semantic dementia.
AB  - A novel, non-verbal test of semantic feature knowledge is introduced, enabling
      subordinate knowledge of four important concept attributes--colour, sound,
      environmental context and motion--to be individually probed. This methodology
      provides more specific information than existing non-verbal semantic tests about
      the status of attribute knowledge relating to individual concept representations.
      Performance on this test of a group of 12 patients with semantic dementia (10
      male, mean age: 64.4 years) correlated strongly with their scores on more
      conventional tests of semantic memory, such as naming and word-to-picture
      matching. The test's overlapping structure, in which individual concepts were
      probed in two, three or all four modalities, provided evidence of performance
      consistency on individual items between feature conditions. Group and individual
      analyses revealed little evidence for differential performance across the four
      feature conditions, though sound and colour correlated most strongly, and motion
      least strongly, with other semantic tasks, and patients were less accurate on the
      motion features of living than non-living concepts (with no such conceptual
      domain differences in the other conditions). The results are discussed in the
      context of their implications for the place of semantic dementia within the
      classification of progressive aphasic syndromes, and for contemporary models of
      semantic representation and organization.

PMID- 16585053
TI  - Marijuana use is associated with a reorganized visual-attention network and
      cerebellar hypoactivation.
AB  - Attention and memory deficits have been reported in heavy marijuana users, but
      these effects may be reversible after prolonged abstinence. It remains unclear
      whether the reversibility of these cognitive deficits indicates that chronic
      marijuana use does not alter cortical networks, or that such changes occur but
      the brain adapts to the drug-induced changes. Blood oxygenation-level dependent
      (BOLD) functional MRI (fMRI) was performed in 24 chronic marijuana users (12
      abstinent and 12 active) and 19 age-, sex- and education-matched control subjects
      during a set of visual-attention tasks with graded levels of difficulty.
      Neuropsychological tests were also administered on each subject. The two
      marijuana user groups showed no significant difference in usage pattern
      (frequency or duration of use, age of first use, cumulative joints used, averaged
      >2000 joints) or estimated cumulative lifetime exposure of Delta-9
      tetrahydrocannabinol (THC) (mean 168 +/- 45 versus 244 +/- 135 g). Despite
      similar task and cognitive test performance compared with control subjects,
      active and abstinent marijuana users showed decreased activation in the right
      prefrontal, medial and dorsal parietal, and medial cerebellar regions, but
      greater activation in various frontal, parietal and occipital brain regions
      during the visual-attention tasks (all with P < or = 0.001, corrected, cluster
      level). However, the BOLD signals in the right frontal and medial cerebellar
      regions normalized with duration of abstinence in the abstinent users. Active
      marijuana users, with positive urine tests for THC, showed greater activation in
      the frontal and medial cerebellar regions than abstinent marijuana users and
      greater usage of the reserve network (regions with load effect), suggesting a
      neuroadaptive state. Both earlier age of first use and greater estimated
      cumulative dose of THC exposure were related to lower BOLD signals in the right
      prefrontal region and medial cerebellum. The altered BOLD activation pattern in
      the attention network and hypoactivation of the cerebellum suggest neuroadaptive
      processes or alteration of brain development in chronic marijuana users. These
      changes also may be related to marijuana-induced alteration in resting cerebral
      blood volume/flow or downregulation of cannabinoid (CB1) receptors. The greater
      activation in the active compared with abstinent marijuana users demonstrates a
      neuroadaptive state in the setting of active marijuana use, while the long-term
      chronic effect of marijuana on the altered brain network may be reversible with
      prolonged abstinence.

PMID- 16585054
TI  - Disease severity in dominant Emery Dreifuss is increased by mutations in both
      emerin and desmin proteins.
AB  - Individuals with the same genetic disorder often show remarkable differences in
      clinical severity, a finding generally attributed to the genetic background. We
      identified two patients with genetically proven Emery-Dreifuss muscular dystrophy
      (EDMD) who followed an unusual course and had uncommon clinicopathological
      findings. We hypothesized digenic inheritance and looked for additional molecular
      explanations. Mutations in additional separate genes were identified in both
      patients. The first patient was a member of a family with molecularly proven X
      linked EDMD. However, the clinical features were unusually severe for this
      condition in the propositus: he presented at 2.5 years with severe proximal
      weakness and markedly elevated serum creatine kinase. Muscle weakness rapidly
      progressed, leading to loss of independent ambulation by the age of 12. In
      addition, the patient developed cardiac conduction system disease requiring
      pacing at the age of 11 and severe dilated cardiomyopathy in the early teens.
      Despite pacing, he had several syncopal episodes attributed to ventricular
      dysrhythmias. As these resemble the cardiac features of patients with the
      autosomal dominant variant of EDMD, we examined the lamin A/C gene, identifying a
      de-novo mutation in the propositus. The second patient had a cardioskeletal
      myopathy, similar to his mother who had died more than 20 years previously.
      Because of the dominant family history, a laminopathy was suspected and a
      mutation in exon 11 of the LMNA gene was identified. This mutation, however, was
      not present in his mother, but instead, surprisingly, was identified in his
      virtually asymptomatic father. Unusual accumulations of desmin found in the
      cardiac muscle of the propositus prompted us to examine the desmin gene in this
      patient, and in so doing, we identified a desmin mutation, in addition to the
      LMNA mutation in the propositus. These cases suggest that separate mutations in
      related proteins that are believed to interact, or that represent different parts
      of a presumed functional pathway, may synergistically contribute to disease
      severity in autosomal dominant EDMD. Furthermore, digenic inheritance may well
      contribute to the clinical severity of many other neuromuscular disorders.

PMID- 16585055
TI  - A systematic review of empirical research on self-reported racism and health.
AB  - This paper reviews 138 empirical quantitative population-based studies of self
      reported racism and health. These studies show an association between self
      reported racism and ill health for oppressed racial groups after adjustment for a
      range of confounders. The strongest and most consistent findings are for negative
      mental health outcomes and health-related behaviours, with weaker associations
      existing for positive mental health outcomes, self-assessed health status, and
      physical health outcomes. Most studies in this emerging field have been published
      in the past 5 years and have been limited by a dearth of cohort studies, a lack
      of psychometrically validated exposure instruments, poor conceptualization and
      definition of racism, conflation of racism with stress, and debate about the
      aetiologically relevant period for self-reported racism. Future research should
      examine the psychometric validity of racism instruments and include these
      instruments, along with objectively measured health outcomes, in existing large
      scale survey vehicles as well as longitudinal studies and studies involving
      children. There is also a need to gain a better understanding of the perception,
      attribution, and reporting of racism, to investigate the pathways via which self
      reported racism affects health, the interplay between mental and physical health
      outcomes, and exposure to intra-racial, internalized, and systemic racism.
      Ensuring the quality of studies in this field will allow future research to
      reveal the complex role that racism plays as a determinant of population health.

PMID- 16585057
TI  - Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis
      development in ApoE-deficient mice.
AB  - The cellular composition of an atherosclerotic lesion is determined by cell
      infiltration, proliferation, and apoptosis. The tumor suppressor gene
      retinoblastoma (Rb) has been shown to regulate both cell proliferation and cell
      death in many cell types. To study the role of macrophage Rb in the development
      of atherosclerosis, we used apoE-deficient mice with a macrophage-restricted
      deletion of Rb (Rb(del) mice) and control littermates (Rb(fl) mice). After 12 wk
      feeding a cholesterol-rich diet, the Rb(del) mice showed a 51% increase in
      atherosclerotic lesion area with a 39% increase in the relative number of
      advanced lesions. Atherosclerotic lesions showed a 13% decrease in relative
      macrophage area and a 46% increase in relative smooth muscle cell area,
      reflecting the more advanced state of the lesions. The increase in
      atherosclerosis was independent of in vitro macrophage modified lipoprotein
      uptake or cytokine production. Whereas macrophage-restricted Rb deletion did not
      affect lesional macrophage apoptosis, a clear 2.6-fold increase in lesional
      macrophage proliferation was observed. These studies demonstrate that macrophage
      Rb is a suppressing factor in the progression of atherosclerosis by reducing
      macrophage proliferation.

PMID- 16585058
TI  - Nicotinic acid adenine dinucleotide phosphate and cyclic ADP-ribose regulate
      TRPM2 channels in T lymphocytes.
AB  - TRPM2 (previously designated TRPC7 or LTRPC2) is a Ca2+-permeable nonselective
      cation channel that contains a C-terminal enzymatic domain with pyrophosphatase
      activity, which specifically binds ADP-ribose. Cyclic ADP-ribose (cADPR) and
      hydrogen peroxide (H2O2) can facilitate ADPR-mediated activation of
      heterologously expressed TRPM2. Here, we show that the two Ca2+-mobilizing second
      messengers cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide
      phosphate (NAADP) strongly activate natively expressed TRPM2 channels in Jurkat T
      cells. TRPM2 activation by both agonists can be partially suppressed by the ADPR
      antagonist adenosine monophosphate (AMP), which suggests that cADPR and NAADP
      lead to mobilization of endogenous ADPR presumably via metabolic conversion. The
      remaining channel activity is due to direct gating of TRPM2 by the two agonists
      and can be completely suppressed by 8-Br-cADPR, which suggests that cADPR and
      NAADP share a common binding site on TRPM2 that can regulate TRPM2 activity in
      synergy with ADPR. We conclude that cADPR and NAADP, in combination with ADPR,
      represent physiological co-activators of TRPM2 that contribute to Ca2+ influx in
      T lymphocytes and presumably other cell types that express this channel.

PMID- 16585059
TI  - Metallothionein prolongs survival and antagonizes senescence-associated
      cardiomyocyte diastolic dysfunction: role of oxidative stress.
AB  - Senescence is accompanied by oxidative stress and cardiac dysfunction, although
      the link between the two remains unclear. This study examined the role of
      antioxidant metallothionein on cardiomyocyte function, superoxide generation, the
      oxidative stress biomarker aconitase activity, cytochrome c release, and
      expression of oxidative stress-related proteins, such as the GTPase RhoA and
      NADPH oxidase protein p47phox in young (5-6 mo) and aged (26-28 mo) FVB wild-type
      (WT) and cardiac-specific metallothionein transgenic mice. Metallothionein mice
      showed a longer life span (by approximately 4 mo) than FVB mice evaluated by the
      Kaplan-Meier survival curve. Compared with young cardiomyocytes, aged myocytes
      displayed prolonged TR(90), reduced tolerance to high stimulus frequency, and
      slowed intracellular Ca2+ decay, all of which were nullified by metallothionein.
      Aging increased superoxide generation, active RhoA abundance, cytochrome c
      release, and p47phox expression and suppressed aconitase activity without
      affecting protein nitrotyrosine formation in the hearts. These aging-induced
      changes in oxidative stress and related protein biomarkers were attenuated by
      metallothionein. Aged metallothionein mouse myocytes were more resistant to the
      superoxide donor pyrogallol-induced superoxide generation and apoptosis. In
      addition, aging-associated prolongation in TR90 was blunted by the Rho kinase
      inhibitor Y-27632. Collectively, our data demonstrated that metallothionein may
      alleviate aging-induced cardiac contractile defects and oxidative stress, which
      may contribute to prolonged life span in metallothionein transgenic mice.

PMID- 16585060
TI  - Glomerular podocytes contain neuron-like functional synaptic vesicles.
AB  - Although patients with chronic renal failure are increasing worldwide, many
      aspects of kidney biology remain to be elucidated. Recent research has uncovered
      several molecular properties of the glomerular filtration barrier, in which
      podocytes, highly differentiated, ramified cells that enwrap the glomerular
      basement membrane, have been reported to be mainly responsible for filter's
      selectivity. We previously described that podocytes express Rab3A, a GTPase
      restricted to cell types that are capable of highly regulated exocytosis, such as
      neuronal cells. Here, we first demonstrate by a proteomic study that Rab3A in
      podocytes coimmmunoprecipitates with molecules once thought to be synapse
      specific. We then show that podocytes possess structures resembling synaptic
      vesicles, which contain glutamate, coexpress Rab3A and synaptotagmin 1, and
      undergo spontaneous and stimulated exocytosis and recycling, with glutamate
      release. Finally, from the results of a cDNA microarray study, we describe the
      presence of a series of neuron- and synapse-specific molecules in normal human
      glomeruli and confirm the glomerular protein expression of both metabotropic and
      ionotropic glutamate receptors. These data point toward a synaptic-like mechanism
      of communication among glomerular cells, which perfectly fits with the molecular
      composition of the glomerular filter and puts in perspective several previous
      observations, proposing a different working hypothesis for understanding
      glomerular signaling dynamics.

PMID- 16585061
TI  - Purified human hematopoietic stem cells contribute to the generation of
      cardiomyocytes through cell fusion.
AB  - To obtain insights into the cardiomyogenic potential of hematopoietic tissue, we
      intravenously (i.v.) injected purified hematopoietic stem/progenitor cells into
      newborn recipients that may fully potentiate the developmental plasticity of stem
      cells. Transplantation of mouse bone marrow (BM) lineage antigen-negative (Lin-)
      cells resulted in the generation of the cells that displayed cardiomyocyte
      specific antigenic profiles and contractile function when transplanted into
      syngeneic newborn recipients. To clarify the mechanism underlying the
      cardiomyogenic potential, green fluorescent protein (GFP)-labeled BM Lin-ScaI+
      hematopoietic progenitors were transplanted into neonatal mice constitutively
      expressing cyan fluorescence protein (CFP). Lambda image acquisition and linear
      unmixing analysis using confocal microscopy successfully separated GFP and CFP,
      and revealed that donor GFP+ cardiomyocytes coexpressed host-derived CFP. We
      further reconstituted human hemopoietic- and immune systems in mice by injecting
      human cord blood (CB)-derived Lin-CD34+CD38- hematopoietic stem cells (HSCs) into
      neonatal T cell(-)B cell(-)NK cell- immune-deficient NOD/SCID/IL2rgamma(null)
      mice. Fluoroescence in situ hybridization analysis of recipient cardiac tissues
      demonstrated that human and murine chromosomes were colocalized in the same
      cardiomyocytes, indicating that cell fusion occurred between human hematopoietic
      progeny and mouse cardiomyocytes. These syngeneic- and xenogeneic neonatal
      transplantations provide compelling evidence that hematopoietic stem/progenitor
      cells contribute to the postnatal generation of cardiomyocytes through cell
      fusion, not through transdifferentiation.

PMID- 16585062
TI  - FAK-dependent regulation of myofibroblast differentiation.
AB  - Fibroblasts and myofibroblasts both participate in wound healing. Transforming
      growth factor beta (TGFbeta) induces fibroblasts to differentiate into
      myofibroblasts, whereas fibroblast growth factor and heparin (FGF/h) induce
      myofibroblasts to "de-differentiate" into fibroblasts. TGFbeta induces expression
      of smooth muscle alpha actin (SMalphaA) and incorporation into in stress fibers,
      a phenotype of differentiated myofibroblasts. Additionally, TGFbeta induces the
      expression of fibronectin and fibronectin integrins. Fibronectin-generated
      signals contribute to the TGFbeta-mediated myofibroblast differentiation. Because
      fibronectin signals are transmitted through focal adhesion kinase (FAK), it was
      predicted that FAK would be essential to TGFbeta-mediated myofibroblast
      differentiation. To determine whether the FAK signaling pathway is required for
      myofibroblast differentiation, we used two approaches to decrease FAK in mouse
      embryo fibroblasts (MEFs): 1) FAK +/+ MEFs, in which FAK protein expression was
      greatly decreased by short hairpin RNA (shRNA), and 2) FAK -/- MEFs, which lack
      FAK. In both cases, the majority of cells were myofibroblasts, expressing
      SMalphaA in stress fibers even after treatment with FGF/h. Furthermore, both the
      surface expression of FGFRs and FGF signaling were greatly reduced in FAK -/-
      [corrected]MEFs. We conclude that FAK does not contribute to TGFbeta-dependent
      myofibroblast differentiation. Instead, FAK was necessary for FGF/h signaling in
      down-regulating expression of SMalphaA, which is synonymous with myofibroblast
      differentiation. FAK activation could contribute to regulating myofibroblast
      differentiation, thereby ameliorating fibrosis.

PMID- 16585063
TI  - Allergen cleavage by effector cell-derived proteases regulates allergic
      inflammation.
AB  - The key event of allergic inflammation, allergen-induced crosslinking of mast
      cell-bound IgE antibodies, is accompanied by release of inflammatory mediators,
      cytokines, and proteases, in particular beta-tryptase. We provide evidence that
      protease-mediated cleavage of allergens represents a mechanism that regulates
      allergen-induced mast cell activation. When used in molar ratios as they occur in
      vivo, purified beta-tryptase cleaved major grass and birch pollen allergens,
      resulting in defined peptide fragments as mapped by mass spectrometry. Tryptase
      cleaved allergens showed reduced IgE reactivity and allergenic activity. The
      biological relevance is demonstrated by the fact that lysates from activated
      human mast cells containing tryptase levels as they occur in vivo cleaved
      allergens. Additionally, protamine, an inhibitor of heparin-dependent effector
      cell proteases, augmented allergen-induced release of mediators from effector
      cells. Protease-mediated allergen cleavage may represent an important mechanism
      for terminating allergen-induced effector cell activation.

PMID- 16585065
TI  - PowQ: a user-friendly package for the design of variance component multipoint
      linkage analysis studies.
AB  - A user-friendly, graphical package for power evaluation and enhancement planning
      through variance component linkage analysis in a multipoint framework.

PMID- 16585066
TI  - Identification of biochemical networks by S-tree based genetic programming.
AB  - MOTIVATION: Most previous approaches to model biochemical networks have focused
      either on the characterization of a network structure with a number of components
      or on the estimation of kinetic parameters of a network with a relatively small
      number of components. For system-level understanding, however, we should examine
      both the interactions among the components and the dynamic behaviors of the
      components. A key obstacle to this simultaneous identification of the structure
      and parameters is the lack of data compared with the relatively large number of
      parameters to be estimated. Hence, there are many plausible networks for the
      given data, but most of them are not likely to exist in the real system. RESULTS:
      We propose a new representation named S-trees for both the structural and
      dynamical modeling of a biochemical network within a unified scheme. We further
      present S-tree based genetic programming to identify the structure of a
      biochemical network and to estimate the corresponding parameter values at the
      same time. While other evolutionary algorithms require additional techniques for
      sparse structure identification, our approach can automatically assemble the
      sparse primitives of a biochemical network in an efficient way. We evaluate our
      algorithm on the dynamic profiles of an artificial genetic network. In 20 trials
      for four settings, we obtain the true structure and their relative squared errors
      are <5% regardless of releasing constraints about structural sparseness. In
      addition, we confirm that the proposed algorithm is robust within +/-10% noise
      ratio. Furthermore, the proposed approach ensures a reasonable estimate of a real
      yeast fermentation pathway. The comparatively less important connections with non
      zero parameters can be detected even though their orders are below 10(-2). To
      demonstrate the usefulness of the proposed algorithm for real experimental
      biological data, we provide an additional example on the transcriptional network
      of SOS response to DNA damage in Escherichia coli. We confirm that the proposed
      algorithm can successfully identify the true structure except only one relation.

PMID- 16585068
TI  - Global dynamics of biological systems from time-resolved omics experiments.
AB  - The emergent properties of biological systems, organized around complex networks
      of irregularly connected elements, limit the applications of the direct
      scientific method to their study. The current lack of knowledge opens new
      perspectives to the inverse scientific paradigm where observations are
      accumulated and analysed by advanced data-mining techniques to enable a better
      understanding and the formulation of testable hypotheses about the structure and
      functioning of these systems. The current technology allows for the wide
      application of omics analytical methods in the determination of time-resolved
      molecular profiles of biological samples. Here it is proposed that the theory of
      dynamical systems could be the natural framework for the proper analysis and
      interpretation of such experiments. A new method is described, based on the
      techniques of non-linear time series analysis, which is providing a global view
      on the dynamics of biological systems probed with time-resolved omics
      experiments.

PMID- 16585064
TI  - ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage
      oligomeric matrix protein.
AB  - Degradative fragments of cartilage oligomeric matrix protein (COMP) have been
      observed in arthritic patients. The physiological enzyme(s) that degrade COMP,
      however, remain unknown. We performed a yeast two-hybrid screen (Y2H) to search
      for proteins that associate with COMP to identify an interaction partner that
      might degrade it. One screen using the epidermal growth factor (EGF) domain of
      COMP as bait led to the discovery of ADAMTS-7. Rat ADAMTS-7 is composed of 1595
      amino acids, and this protein exhibits higher expression in the musculoskeletal
      tissues. COMP binds directly to ADAMTS-7 in vitro and in native articular
      cartilage. ADAMTS-7 selectively interacts with the EGF repeat domain but not with
      the other three functional domains of COMP, whereas the four C-terminal TSP
      motifs of ADAMTS-7 are required and sufficient for association with COMP. The
      recombinant catalytic domain and intact ADAMTS-7 are capable of digesting COMP in
      vitro. The enzymatic activity of ADAMTS-7 requires the presence of Zn2+ and
      appropriate pH (7.5-9.5), and the concentration of ADAMTS-7 in cartilage and
      synovium of patients with rheumatoid arthritis is significantly increased as
      compared to normal cartilage and synovium. ADAMTS-7 is the first
      metalloproteinase found to bind directly to and degrade COMP.

PMID- 16585069
TI  - A fast coarse filtering method for peptide identification by mass spectrometry.
AB  - MOTIVATION: We reformulate the problem of comparing mass-spectra by mapping
      spectra to a vector space model. Our search method leverages a metric space
      indexing algorithm to produce an initial candidate set, which can be followed by
      any fine ranking scheme. RESULTS: We consider three distance measures integrated
      into a multi-vantage point index structure. Of these, a semi-metric fuzzy-cosine
      distance using peptide precursor mass constraints performs the best. The index
      acts as a coarse, lossless filter with respect to the SEQUEST and ProFound
      scoring schemes, reducing the number of distance computations and returned
      candidates for fine filtering to about 0.5% and 0.02% of the database
      respectively. The fuzzy cosine distance term improves specificity over a peptide
      precursor mass filter, reducing the number of returned candidates by an order of
      magnitude. Run time measurements suggest proportional speedups in overall search
      times. Using an implementation of ProFound's Bayesian score as an example of a
      fine filter on a test set of Escherichia coli protein fragmentation spectra, the
      top results of our sample system are consistent with that of SEQUEST.

PMID- 16585070
TI  - Pandemic influenza: using evidence on vaccines and antivirals for clinical
      decisions and policy making.

PMID- 16585071
TI  - Antioxidant therapy in idiopathic pulmonary fibrosis: hope is kindled.

PMID- 16585072
TI  - The cellular impacts of diesel exhaust particles: beyond inflammation and death.

PMID- 16585073
TI  - Interleukin-10, age and acute lung injury genetics: the action is in the
      interaction.

PMID- 16585074
TI  - Obstructive sleep apnoea: time for a radical change?

PMID- 16585075
TI  - Interleukin-10 polymorphism in position -1082 and acute respiratory distress
      syndrome.
AB  - The GG genotype of the interleukin (IL)-10 promoter polymorphism in position 
      1082 (-1082GG) has been associated with increased IL-10 production. The current
      authors hypothesised that the -1082GG genotype is associated with the development
      of, and outcomes in, acute respiratory distress syndrome (ARDS). A nested case
      control study was conducted in 211 Caucasian cases of ARDS and 429 controls who
      were admitted to an intensive care unit with sepsis, trauma, aspiration or
      massive transfusions. Cases were followed for organ failure and 60-day mortality.
      The -1082GG genotype was associated with the development of ARDS, but only in the
      presence of a significant interaction between the -1082GG genotype and age. Among
      patients with ARDS, the -1082GG genotype was associated with decreased severity
      of illness on admission, lower daily organ dysfunction scores and lower 60-day
      mortality. In conclusion, the high interleukin-10-producing -1082GG genotype may
      be associated with variable odds for acute respiratory distress syndrome
      development depending on age. Among those with acute respiratory distress
      syndrome, the -1082GG genotype is associated with lower mortality and organ
      failure. Further studies are needed to confirm these findings.

PMID- 16585076
TI  - Genetic association between COPD and polymorphisms in TNF, ADRB2 and EPHX1.
AB  - There is evidence of a hereditary component in chronic obstructive pulmonary
      disease (COPD). A number of genetic association studies have been performed to
      find susceptibility genes of COPD. The current authors performed a case-control,
      genetic-association study and a meta-analysis of 16 studies, involving seven
      polymorphisms in three well-studied genes: microsomal epoxide hydroxylase
      (EPHX1); tumour necrosis factor; and beta2-adrenoreceptor. A total of 492
      Caucasian smokers and former smokers were recruited from hospital databases and
      population cohort studies. In the present study, a protective effect of the EPHX1
      Tyr113His polymorphism was found (homozygous odds ratio (OR) 0.5). In the meta
      analysis, homozygotes for this single nucleotide polymorphism (SNP) also had a
      pooled OR of 0.5. The same effect has been found in several lung cancer studies.
      Effects for other candidate SNPs were weak or statistically insignificant, and
      probable genotyping error was common. In conclusion, the present data and meta
      analysis support a role for microsomal epoxide hydroxylase in the aetiology of
      chronic obstructive pulmonary disease.

PMID- 16585077
TI  - Body weight and comorbidity predict mortality in COPD patients treated with
      oxygen therapy.
AB  - The aim of this study was to investigate the association between clinical
      variables and all-cause and respiratory mortality in patients with chronic
      obstructive pulmonary disease (COPD) undergoing long-term oxygen therapy (LTOT).
      The authors retrospectively studied a historic cohort of 128 patients with COPD
      (126 males, mean age+/-SD 68.9+/-9.7 yrs, body mass index (BMI) 25.1+/-4.5 kg.m
      2, and forced expiratory volume in one second 25.4+/-8.8% predicted), who were
      being treated with long-term oxygen therapy in a tertiary teaching hospital
      between 1992 and 1999. Comorbidity, assessed with the Charlson Index, was present
      in 38% of the patients. Vital status and cause of death were assessed through the
      population death registry. A total of 78 patients (61%) had died by the end of
      follow-up. Three-year survival was 55%. Death was due to respiratory causes in
      77% of cases. On Cox analysis, BMI<25 kg.m-2, comorbid conditions, age>or=70 yrs
      and cor pulmonale were associated with all-cause mortality. The BMI and
      comorbidity were the only significant predictive factors when the analysis was
      restricted to respiratory mortality. In conclusion, body mass index<25 kg.m-2 and
      comorbidity were predictors of all-cause and respiratory mortality in a cohort of
      chronic obstructive pulmonary disease patients treated with long-term oxygen
      therapy. These factors should be taken into account when considering the
      management and prognosis of these patients.

PMID- 16585078
TI  - Short-burst oxygen therapy for COPD patients: a 6-month randomised, controlled
      study.
AB  - Short-burst oxygen therapy (SBOT) remains widely advocated for patients with
      chronic obstructive pulmonary disease (COPD), despite a lack of supporting
      evidence. The aim of this randomised, double-blind, placebo-controlled, parallel
      group study was to determine whether SBOT improves health-related quality of life
      (HRQL) or reduces acute healthcare utilisation in patients discharged following
      an acute exacerbation of COPD. Consecutive patients were screened; 78 of 331 were
      eligible for randomisation to cylinder oxygen, cylinder air or usual care
      following discharge. Patients were elderly with high acute healthcare
      utilisation, forced expiratory volume in one second of <1 L and had dyspnoea
      limiting daily activity but were not hypoxaemic at rest. Over the 6-month study
      period, there were no significant differences between patient groups in HRQL
      (Chronic Respiratory Questionnaire (CRQ), 36-item Short-Form Health Survey,
      Hospital Anxiety and Depression Scale) except for CRQ emotion domain. There were
      no significant differences in acute healthcare utilisation. Time to readmission
      was greatest in the usual care group. Cylinder use was high initially, but
      rapidly fell to very low levels within weeks in both cylinder oxygen and air
      groups. In conclusion, the availability of short-burst oxygen therapy for chronic
      obstructive pulmonary disease patients discharged from hospital following an
      acute exacerbation did not improve health-related quality of life or reduce acute
      healthcare utilisation. These results provide no support for the widespread use
      of short-burst oxygen therapy.

PMID- 16585079
TI  - Incidence of asthma among workers exposed to sulphur dioxide and other irritant
      gases.
AB  - The aim of the present study was to investigate whether repeated peak exposure
      (gassings) to sulphur dioxide (SO2) and other irritant gases increases the risk
      of new-onset asthma. A questionnaire was sent to 4,112 sulphite workers, of whom
      1,919 completed the questionnaire and 396 completed the short-form questionnaire,
      which was sent out as a last reminder. A sample of 130 nonrespondents completed a
      telephone interview using the short-form questionnaire. The incidence of adult
      onset, physician-diagnosed asthma during employment duration was analysed in
      relation to exposure to SO2 and gassings giving rise to respiratory symptoms.
      Incidence rates, as well as incidence rate ratios with 95% confidence interval
      (CI), were calculated. Further Cox regression models were used allowing
      assessment of hazard ratios (HR) stratified for sex and adjusted for atopy,
      smoking habits and age. The incidence rate for asthma among sulphite mill workers
      reporting gassings of SO2 was 6.2 out of 1,000 person-yrs, compared with 1.9 out
      of 1,000 person-yrs among subjects unexposed to SO2 and any gassings (HR (95% CI)
      4.0 (2.1-7.7)). Among males reporting gassings to SO2, the HR (95% CI) for asthma
      was 5.8 (2.6-13) compared with unexposed males. In conclusion, repeated peak
      exposure to sulphur dioxide increased the incidence of asthma during work in
      sulphite pulp mills, which supports the hypothesis of irritant-induced asthma.

PMID- 16585080
TI  - Mechanisms of dyspnoea and its language in patients with asthma.
AB  - This study hypothesises that regardless of the global score of dyspnoea
      intensity, different descriptors may be selected by asthmatic patients during
      short cardiopulmonary exercise test (sCPET) and methacholine (Mch) inhalation. It
      also examines whether different qualitative dyspnoea sensations can help explain
      the underlying mechanisms of the symptom. Minute ventilation (V'E), tidal volume
      (VT) and inspiratory capacity (IC) were measured in 22 stable asthmatic patients,
      and the sensation of dyspnoea during Mch inhalation and sCPET was quantitatively
      (Borg scale) and qualitatively (descriptors) assessed. The work rate and oxygen
      uptake (V'O2) were also measured during sCPET. Airway obstruction and
      hyperinflation, as measured by IC reduction, were the best correlates for
      dyspnoea with Mch. During sCPET, changes in WR, V'O2, V'E and VT significantly
      correlated with Borg score, with V'E being the best predictor of dyspnoea; IC
      decreased in eight patients. Furthermore, chest tightness (68%) was the highest
      reported descriptor during Mch inhalation, whereas work/effort (72%) was the
      highest during sCPET. In conclusion, obstruction/hyperinflation and work rate are
      highly reliable predictors of Borg rating of dyspnoea during methacholine
      inhalation and short cardiopulmonary exercise testing, respectively. Regardless
      of the global score of intensity dyspnoea, different descriptors may be selected
      by patients during short cardiopulmonary exercise testing and methacholine
      inhalation. Various qualities of dyspnoea result from different
      pathophysiological abnormalities.

PMID- 16585081
TI  - Symptom burden of sleep-disordered breathing in mild-to-moderate congestive heart
      failure patients.
AB  - The symptom burden resulting from sleep-disordered breathing (SDB) in patients
      with mild-to-moderate congestive heart failure (CHF) is unclear. The current
      authors monitored 24-h activity levels and compared subjective and objective
      measures of daytime sleepiness in 39 CHF patients, New York Heart Association
      class 2-3, on optimal medication. A total of 22 patients were classified as SDB
      (apnoea/hypopnoea index (AHI) median (range) 22.3 (16.6-100) events.h-1), and 17
      as no SDB (NoSDB; AHI 3.7 (0-12.3) events.h-1). SDB was defined as AHI>or=15
      events.h-1. Patients were assessed by 24-h activity monitoring (actigraphy) for a
      period of up to 14 days, a single objective sleepiness test (Oxford Sleep
      Resistance test) and Epworth Sleepiness Scale. The duration of daytime activity
      was significantly shorter in the SDB group compared with the NoSDB group. The SDB
      group also had increased time in bed and poorer sleep quality, as shown by the
      fragmentation index. Objectively the SDB group when compared with the NoSDB group
      were significantly sleepier, subjectively the groups did not differ. The amount
      of napping was similar for both groups. Despite the lack of subjective symptoms
      of daytime sleepiness, congestive heart failure patients with sleep-disordered
      breathing were objectively sleepier during the day and had reduced daytime
      activity with longer periods in bed and poorer sleep quality when compared with
      those without sleep-disordered breathing.

PMID- 16585082
TI  - Antioxidant status in patients with sleep apnoea and impact of continuous
      positive airway pressure treatment.
AB  - The episodes of hypoxia/re-oxygenation associated with the respiratory
      disturbances observed in patients with obstructive sleep apnoea syndrome (OSAS)
      may induce the generation of oxygen free radicals. Indeed, several studies
      suggest that OSAS is associated with oxidative stress. The present study tested
      the hypothesis that patients with OSAS have an alteration in antioxidant
      defences. The plasma levels of total antioxidant status (TAS), glutathione
      peroxidase (GPX), gamma-glutamyltransferase (GGT), vitamins A, E, B12 and folate,
      and homocysteine were determined in 47 patients with OSAS and 37 healthy
      subjects. Of these, 27 patients who used continuous positive airway pressure
      (CPAP) for >4 h.night-1 were re-examined 12 months later. Patients with OSAS had
      lower TAS (1.4+/-0.16 versus 1.50+/-0.10 mmol.L-1), vitamin A (64+/-19 versus
      74+/-17 microg.dL-1) and vitamin E levels (1,525+/-499 versus 1,774+/-503
      microg.dL-1), and increased values of GGT (42+/-22 versus 32+/-16 U.L-1) than
      controls. There was no difference between groups in GPX, homocysteine, vitamin
      B12 and folate plasma levels. CPAP treatment normalised the levels of TAS (1.50+/
      0.13 mmol.L-1) and the activity of GGT (30+/-14 U.L-1) without any influence on
      vitamins levels. In conclusion, the results indicate that patients with
      obstructive sleep apnoea syndrome have a decreased antioxidant capacity that is
      partially reversed by continuous positive airway pressure treatment.

PMID- 16585083
TI  - Continuous positive airway pressure treatment for sleep apnoea: compliance
      increases with time in continuing users.
AB  - Continuous positive airway pressure (CPAP) remains the best treatment for sleep
      apnoea syndrome (SAS). In the 1990s, many authors reported on daily compliance,
      but all of the studies utilised relatively short periods of follow-up that did
      not exceed a few years. The mean annual rate of CPAP use in patients with SAS was
      prospectively recorded. In the current study, the results are presented along
      with compliance data from patients who started CPAP between 1991 and 1998 and
      were still using it by the end of 2003. The cohort was chosen in order to obtain
      >or=5 yrs of follow-up for each patient. In total, there were 204 patients. For
      the whole group, mean+/-sd compliance reached 321+/-90 and 393+/-84 min after 1
      and 10 yrs, respectively. There was no significant change in the first 2 yrs,
      with a significant increase from the third year onwards. Compliance, or its
      evolution over time, was not correlated either to the baseline polysomnographical
      data (except slightly for the CPAP pressure), to the difference of these data
      before and under CPAP therapy, to the age of retirement or to changes in the
      marital status. In conclusion, very long-term compliance with continuous positive
      airway pressure increases by a mean of 8 min.day-1 per year of follow-up in
      patients with sleep apnoea syndrome.

PMID- 16585084
TI  - Sources of variation in forced expiratory volume in one second and forced vital
      capacity.
AB  - Published prediction equations for lung function differ considerably, but the
      components of population variation responsible for the differences are unknown.
      Data were analysed for 6,323 never-smoking adults who did not report wheeze or
      asthma, from 42 centres participating in the European Community Respiratory
      Health Survey. Means and components of variance were estimated for males and
      females aged 20-24 yrs, and the relationships with age and height were examined
      in those aged 25-44 yrs. Mean lung function for those aged 20-24 yrs differed
      between centres, but variation could not be wholly attributed to differences in
      population or equipment. The maximum difference in means by equipment type was
      101 mL for FVC in males. Equipment differences were not statistically significant
      adjusted for country, but differences in mean forced expiratory volume in one
      second and forced vital capacity by country, adjusted for instrument, were
      statistically significant in males. Differences between centres in relation to
      age and height had less influence on predicted values. In conclusion, there are
      unexplained differences in lung function between ethnically similar nonsmoking
      symptom-free populations. Neither national reference curves nor those based on
      the same ethnic group can be guaranteed to give accurate norms of lung health.

PMID- 16585085
TI  - Do respiratory symptoms predict job choices in teenagers?
AB  - Existing guidelines advise adolescents with asthma and allergies against high
      risk occupations. The aim of the current authors' analyses was to investigate the
      resulting self-selection in a prospective cohort study. The participants of Phase
      II of the International Study of Asthma and Allergies in Childhood in Germany
      (aged 9-11 yrs at baseline) were re-contacted after 7 yrs (response rate was 77%)
      and were asked to complete a questionnaire, which included items on atopic
      diseases. The subjects were also asked about the type of job they would like to
      have in the future (preferred job choice). Exposure to agents with potential
      asthma risk was evaluated using a job exposure matrix. The analyses were
      restricted to those in school-based vocational training programmes without
      occupational exposures. A total of 33% of subjects chose jobs with high asthma
      risk, 23% selected low asthma risk jobs and the remaining adolescents indicated
      jobs without known asthma risk (reference category). There were no statistically
      significant associations between asthma, allergic rhinitis or atopic dermatitis
      and selecting jobs with asthma risk. Participants with allergic rhinitis tended
      to select high risk jobs less frequently. In conclusion, self-selection into low
      risk jobs seems to play a minor role in teenagers with asthma or allergies.

PMID- 16585086
TI  - The role of interleukin-17 during acute rejection after lung transplantation.
AB  - Acute rejection (AR) is an important complication that can occur after lung
      transplantation and constitutes a risk factor for bronchiolitis obliterans
      syndrome, which is characterised by a neutrophilic airway inflammation. The
      specific aim of this study was to investigate the role of interleukin (IL)-17,
      which promotes chemotaxis of neutrophils by inducing IL-8 production, in AR. Cell
      differentials, mRNA and protein levels were quantified in bronchoalveolar lavages
      (BALs) taken from patients at 28 and 90 days after lung transplantation. The
      patient's rejection status was assessed by transbronchial biopsy. An AR was found
      in nine out of the 26 patients examined, 28 days after transplantation. The
      number of BAL neutrophils and lymphocytes were increased in these patients. IL-17
      mRNA and protein levels in the BAL were increased in patients with AR. Analysis
      of BAL obtained at day 90 after transplantation, demonstrated that the increase
      in IL-17 had disappeared, whereas the increase in neutrophils and lymphocytes
      persisted. These data showed that interleukin-17 is temporarily upregulated in
      bronchoalveolar lavage during acute rejection. The number of lymphocytes and
      neutrophils are increased in bronchoalveolar lavage during acute rejection and
      may persist up to 2 months after acute rejection. These findings suggest that
      interleukin-17 is important in the pathophysiology of acute lung rejection.

PMID- 16585087
TI  - Mixed community-acquired pneumonia in hospitalised patients.
AB  - The role of mixed community-acquired pneumonia (CAP) is controversial. The aim of
      the present study was to determine the incidence, principal microbial patterns,
      clinical predictors and course of mixed CAP. The current study included 1,511
      consecutive hospitalised patients with CAP. Of these, 610 (40%) patients had an
      established aetiology. One pathogen was demonstrated in 528 patients and 82 (13%)
      patients had mixed pneumonia. Cases including CAP, by a pyogenic bacteria and a
      complete paired serology for "atypicals", revealed that 82 (13%) patients had
      definite single pyogenic pneumonia and 28 patients (5%) had mixed pyogenic
      pneumonia. In patients with mixed CAP, Streptococcus pneumoniae was the most
      prevalent microorganism (44 out of 82; 54%). The most frequent combination was S.
      pneumoniae with Haemophilus influenzae (17 out of 82; 21%). Influenza virus A and
      S. pneumoniae (five out of 28; 18%) was the most frequent association in the
      mixed pyogenic pneumonia group. No clinical predictors for mixed pneumonias could
      be identified. Patients with mixed pyogenic pneumonia more frequently developed
      shock when compared with patients with single pyogenic pneumonia (18 versus 4%).
      In conclusion, mixed pneumonia occurs in >10% of cases with community-acquired
      pneumonia requiring hospitalisation.

PMID- 16585088
TI  - Tuberculosis screening in migrants in selected European countries shows wide
      disparities.
AB  - Well-established tuberculosis screening units in Western Europe were selectively
      sampled. Three screening units in Norway, two in the UK, one in the Netherlands
      and one in Switzerland were evaluated. The aim of this study was to describe a
      range of service models used at a number of individual tuberculosis units for the
      screening of new entrants into Europe. Semi-structured interviews were conducted
      with clinicians, nurses and administrators from a selected sample of European
      tuberculosis screening units. An outline of key themes to be addressed was
      forwarded to units ahead of scheduled interviews. Themes included the history of
      the unit, structure, processes and outputs involved in screening new entrants for
      tuberculosis. Considerable variation in screening services exists in the
      approaches studied. Units are sited in transit camps or as units within hospital
      facilities. Staff capacity and administration varies from one clinic per week
      with few dedicated staff to fully dedicated units. Only one site recorded
      symptoms; tuberculin testing was universal in children, but varied in adults;
      chest radiograph screening was universal except at one site where a positive
      tuberculin skin test or symptoms were required in those <35 yrs of age before
      ordering a radiograph. Few output data are routinely and systematically
      collected, which hinders comparison and determination of effectiveness and
      efficiency. Service models for screening new immigrants for tuberculosis appear
      to vary in Western Europe. The systematic collection of data would make
      international comparisons between units easier and help draw conclusions that
      might usefully inform service development.

PMID- 16585089
TI  - Crackle-sound recording to monitor airway closure and recruitment in ventilated
      pigs.
AB  - It was hypothesised that the recruitment of atelectatic lung areas is signified
      by changes in the airway and tissue mechanics, and by the appearance of crackle
      activity attributed to the sudden reopening of collapsed airways. The authors
      also assumed that the acoustic activity is an earlier indicator of lung
      recruitment than the change in the overall mechanical state of the lungs. Six
      thoracotomised and mechanically ventilated mini-pigs were studied. Low-frequency
      pulmonary impedance was measured at end-expiratory pauses at transpulmonary
      pressures of 4 and 1 hPa to estimate airway resistance (Raw) and the coefficient
      of lung tissue elastance (H), and tracheal sounds were recorded during subsequent
      slow inflations to 30 hPa, in the control state and following increasing doses of
      i.v. methacholine (Mch). Raw and H were higher at baseline and increased more in
      response to Mch at 1 hPa than at 4 hPa. The crackles detected during the
      subsequent inflations were concentrated around and associated with the
      development of the lower knee of the pressure-volume curve. The number of
      crackles increased faster following the Mch doses and reached statistical
      significance earlier than Raw and H. Crackle recording during mechanical
      ventilation can be employed as a simple method with which to monitor lung
      recruitment-derecruitment.

PMID- 16585090
TI  - The neutrophilic and fibrinolytic response to talc can predict the outcome of
      pleurodesis.
AB  - It was hypothesised that monitoring neutrophil and D-dimer (DD) levels into the
      pleural fluid, after talc instillation, could predict the outcome of pleurodesis.
      The current authors investigated a total of 168 patients with malignant pleural
      effusion, who were treated with talc poudrage. According to the outcome the
      patients were categorised into one of two groups, either successful or failed
      pleurodesis. In all cases, pleural fluid neutrophils and DDs were determined on
      serial measurements at 0, 3, 24 and 48 h after the procedure. The time course of
      these parameters was assessed in both groups and the time point at which they
      could better predict the outcome was further explored. Neutrophils rose rapidly
      after talc poudrage in both groups, reaching a plateau at 24 h, although in
      successful pleurodesis this response was significantly higher. DD dropped
      markedly at 24 h in the group with the successful outcome, but it did not show
      significant changes in the other group. A cut-off value of 61% for neutrophils
      and 61 mg.L-1 for the DD at 24 h yielded the best prognosis for successful
      pleurodesis. The current authors conclude that serial measurements of neutrophil
      and d-dimer values into the pleural fluid after talc poudrage could be used as
      predictors of the outcome of pleurodesis.

PMID- 16585091
TI  - Outcomes and markers in the assessment of chronic obstructive pulmonary disease.
AB  - The clinical presentation of chronic obstructive pulmonary disease (COPD) is
      highly variable, reflecting the interaction of a complex range of pathological
      changes including both pulmonary and systemic effects. The consequences of COPD
      experienced by the patient (i.e. its outcomes) include: symptoms, weight loss,
      exercise intolerance, exacerbations, health-related quality of life, health
      resource use and death. No single measure can reflect the variety of pathological
      effects or adequately describe the nature or severity of COPD. Currently, there
      are few validated markers for assessing COPD and evaluating the effectiveness of
      treatment. The forced expiratory volume in one second has been used as a global
      marker of COPD, but it does not fully reflect the burden of COPD on patients. New
      markers are needed to better characterise the full clinical spectrum of the
      disease and to guide the development and assessment of new and more effective
      therapies. This article considers the distinction between outcomes and markers,
      the various ways in which markers are used and the need for new markers in the
      management of chronic obstructive pulmonary disease. The process of marker
      selection and validation is reviewed and potential new biological, physiological
      and symptomatic markers for chronic obstructive pulmonary disease are assessed.

PMID- 16585092
TI  - Increasing COPD awareness.
AB  - Early diagnosis and smoking cessation are the only available methods to stop the
      progression of chronic obstructive pulmonary disease (COPD). The aim of this
      study was to evaluate the effects of early detection of airflow limitation (AL)
      in a population with high risk for COPD, using spirometric screening. Smokers
      aged 40 yrs with a smoking history of 10 pack-yrs were invited to visit a local
      outpatient chest clinic for simple spirometry (forced expiratory volume in one
      second (FEV1) and forced vital capacity (FVC)). Smoking history was recorded,
      followed by smoking cessation advice relating the results of spirometry to the
      smoking behaviour. Subjects who did not fulfil the above criteria (younger and/or
      nonsmokers) were also screened. A total 110,355 subjects were investigated; they
      were aged 53.5+/-11.5 yrs and 58.2% were males. Of the total amount of subjects,
      64% were current smokers, 25.1% were former smokers and 10.9% were lifelong
      nonsmokers. Spirometry tests were within normal values for 70.3%, and 20.3%
      showed signs of AL: this was mild in 7.6%, moderate in 6.7% and severe in 5.9%.
      The remaining 8.3% of subjects presented with a restrictive pattern of
      ventilatory impairment. Airflow limitation was found in 23% of smokers aged 40
      yrs with a history of 10 pack-yrs. This study concluded that large-scale
      voluntary spirometry screening of the population with high risk for COPD detects
      a large number of subjects with AL.

PMID- 16585093
TI  - Walking with continuous positive airway pressure.
AB  - A ventilator-dependent child had been in the paediatric intensive care unit
      (PICU) ever since birth. As a result, she had fallen behind considerably in her
      development. After 18 months, continuous positive airway pressure was
      successfully administered via a tracheostomy tube with a novel lightweight
      device. This enabled her to walk in the PICU. With this device, the child was
      discharged home where she could walk with an action range of 10 m. Subsequently,
      her psychomotor development improved remarkably. To the authors' knowledge, this
      is the first case report of a patient, adult or paediatric, who could actually
      walk with a sufficient radius of action while receiving long-term respiratory
      support.

PMID- 16585094
TI  - A patient with pancreatitis, anaemia and an intrathoracic tumour. Diagnosis:
      tumour-simulating asymptomatic intrathoracic extramedullary haematopoiesis (EMH)
      in a patient with hereditary spherocytosis.

PMID- 16585095
TI  - Smoking cessation: a critical investigative tool in COPD.

PMID- 16585096
TI  - A day at the European Respiratory Society Congress: passive smoking influences
      both outdoor and indoor air quality.

PMID- 16585097
TI  - COPD: an inhaled corticosteroid-resistant, oral corticosteroid-responsive
      condition.

PMID- 16585098
TI  - The sulphoxidation of S-carboxymethyl-L-cysteine in COPD.

PMID- 16585099
TI  - Urinary incontinence in patients with bronchiectasis.

PMID- 16585100
TI  - Metalloptysis.

PMID- 16585102
TI  - Turn up the heat on health professions education.

PMID- 16585103
TI  - Reducing racial and ethnic disparities in health care: an integral part of
      quality improvement scholarship.

PMID- 16585104
TI  - Development of the Leapfrog methodology for evaluating hospital implemented
      inpatient computerized physician order entry systems.
AB  - The 1999 Institute of Medicine report raised public awareness of the frequency
      and cost of adverse drug events in medicine. In response, in November 2000 a
      coalition of healthcare purchasers announced the formation of the Leapfrog Group,
      an organization dedicated to making "great leaps forward" in the safety and
      quality of health care in America. Their first target-computerized physician
      order entry (CPOE)-was selected specifically for its potential to reduce harm to
      patients from medications. The Leapfrog inpatient CPOE standard included a
      requirement that the organization operating CPOE should demonstrate via a test
      that their inpatient CPOE system can alert physicians to at least 50% of common
      serious prescribing errors. This paper outlines the development of this test
      which evaluates the ability of implemented CPOE systems to prevent the occurrence
      of medication errors that have a high likelihood of leading to adverse drug
      events. A framework was developed to include 12 different categories of CPOE
      based decision support that could prevent prescribing errors leading to adverse
      drug events. A scoring system was developed based on the known frequency and
      severity of adverse drug events. Simulated test patients and accompanying
      simulated test medication orders were developed to evaluate the ability of a CPOE
      system to intercept prescribing errors in all 12 decision support categories. The
      test was validated at a number of inpatient sites using both commercially
      available and custom developed CPOE systems. A web based application was
      developed to allow hospitals to self-administer the evaluation.

PMID- 16585106
TI  - Use of a standardized protocol to decrease medication errors and adverse events
      related to sliding scale insulin.
AB  - PROBLEM: Sliding scale insulin (SSI) is frequently used for inpatient management
      of hyperglycemia and is associated with a large number of medication errors and
      adverse events including hypoglycemia and hyperglycemia. DESIGN: Observational
      before and after study evaluating the impact of implementation of a standardized
      SSI protocol and preprinted physician order form. SETTING: University Hospital in
      Pittsburgh, PA, USA. STRATEGY FOR CHANGE: Guidelines for the use of SSI were
      created by an interdisciplinary committee and implemented in non-intensive care
      units. In addition, a preprinted physician order sheet was developed which
      included the guidelines and an option for ordering one of three standardized
      insulin sliding scales or a patient specific scale. EFFECT OF CHANGE: One year
      after implementation the physician order form was used for 91% of orders and,
      overall, 86% of SSI orders followed the guidelines. The number of prescribing
      errors found on chart review was reduced from 10.3 per 100 SSI patient-days at
      baseline to 1.2 at 1 year (p = 0.03). The number of hyperglycemia episodes 1 year
      after implementation decreased from 55.9 to 16.3 per 100 SSI patient-days.
      LESSONS LEARNT: The protocol was readily accepted by hospital staff and was
      associated with decreased prescribing errors and decreased frequency of
      hyperglycemia.

PMID- 16585105
TI  - How can the principles of complexity science be applied to improve the
      coordination of care for complex pediatric patients?
AB  - Clinical and technological advances in medicine have resulted in more patients
      requiring multidisciplinary care and coordination of services. This is
      particularly challenging in pediatrics, given the dependency of children.
      Coordination of care is a key ingredient of quality care; when suboptimal,
      clinical outcomes and satisfaction can suffer. In this article we view
      coordination of care through the lens of complexity science in an effort to find
      new solutions to this healthcare challenge.

PMID- 16585107
TI  - Building safer systems by ecological design: using restoration science to develop
      a medication safety intervention.
AB  - BACKGROUND: Experts call for stronger safety cultures and transparent reporting
      practices to increase medication safety in today's strained healthcare
      environments. The field of ecological restoration is concerned with the
      effective, efficient, and sustainable repair and recovery of ecosystems that have
      been degraded, damaged, or destroyed. A study was undertaken to determine whether
      the lessons of restoration science can be adapted to the study of medication
      safety issues. METHODS: Working with 26 practitioners, the principles of good
      restoration were used to design and pilot an innovative multifaceted medication
      safety intervention. The intervention included focus groups with practitioners,
      the construction and administration of a research based medication safety
      inventory, repeat digital photography of environmental safety issues, and
      targeted environmental modifications. RESULTS: Participants were most concerned
      about staff education and the physical environment for medication administration.
      Ward staff used the research to build a healthy reporting culture, introduce
      regular discussions of near misses, develop education strategies, redesign
      delivery and storage processes, and renovate the environment. CONCLUSIONS:
      Members of a busy hospital ward successfully adapted methods of restoration
      science to study, redesign, and strengthen medication safety practices and ward
      safety culture within existing resources. Further research will be conducted to
      test the merits of restoration science for health care.

PMID- 16585108
TI  - Participating in a trial in a critical situation: a qualitative study in
      pregnancy.
AB  - BACKGROUND: Randomised controlled trials of interventions in critical situations
      are necessary to establish safety and evaluate outcomes. Pregnant women have been
      identified as a potentially vulnerable population. OBJECTIVE: To explore women's
      experiences of being recruited to ORACLE, a randomised controlled trial of
      antibiotics in pre-term labour. METHODS: Twenty qualitative interviews were
      conducted with women who had participated in ORACLE. Analysis was based on the
      constant comparative method. RESULTS: Women gave prominence to the socioemotional
      aspects of their interactions with healthcare professionals in making decisions
      on trial participation. Comments on the quality of written and spoken information
      were generally favourable, but women's accounts suggest that the stressful nature
      of the situation affected their ability to absorb the information. Women
      generally had poor understanding of trial design and practices. The main
      motivation for trial participation was the possibility of an improved outcome for
      the baby. The second and less prominent motivation was the opportunity to help
      others, but this was conditional on there being no risks associated with trial
      participation. In judging the risks of participation, women seemed to draw on
      "common sense" understandings including a perception that antibiotics were risk
      free. DISCUSSION: Recruitment to trials in critical situations raises important
      questions. Future studies should explore how rigorous governance arrangements for
      trials, particularly in critical situations, can protect participants rather than
      relying on ideals of informed consent that may be impossible to achieve. Future
      research should include a focus on interactions between research candidates and
      professionals involved in recruitment.

PMID- 16585110
TI  - Measuring safety climate in health care.
AB  - AIM: To review quantitative studies of safety climate in health care to examine
      the psychometric properties of the questionnaires designed to measure this
      construct. METHOD: A systematic literature review was undertaken to study sample
      and questionnaire design characteristics (source, no of items, scale type),
      construct validity (content validity, factor structure and internal reliability,
      concurrent validity), within group agreement, and level of analysis. RESULTS:
      Twelve studies were examined. There was a lack of explicit theoretical
      underpinning for most questionnaires and some instruments did not report standard
      psychometric criteria. Where this information was available, several
      questionnaires appeared to have limitations. CONCLUSIONS: More consideration
      should be given to psychometric factors in the design of healthcare safety
      climate instruments, especially as these are beginning to be used in large scale
      surveys across healthcare organisations.

PMID- 16585109
TI  - Unscheduled returns to the emergency department: an outcome of medical errors?
AB  - BACKGROUND: The causes of unscheduled returns to the emergency department (ED)
      within 72 hours of discharge are unclear. A study was undertaken to identify
      factors associated with this quality care indicator. METHODS: 250 cases and 250
      controls from the ED were prospectively studied. Outcomes measured were
      unscheduled returns, post-ED destination, and patient dissatisfaction. Possible
      medical errors (in diagnosis, treatment, prognosis or patient information) and
      errors in follow up care were identified. Other factors examined included chief
      complaint at presentation, discharge diagnosis, level of triage, category of
      treating physician, observation or not, application of emergency treatment,
      ancillary studies, accessibility to ED, ED time band or work shift, day of the
      week, past medical history, and demographic data (age, sex, educational level and
      economic status). RESULTS: The main factor associated with unscheduled returns
      was error in prognosis (odds ratio 18.62, 95% CI 9.60 to 36.09). Advanced age and
      a chief complaint of dyspnoea were also associated with unscheduled returns and
      with admission to hospital. Post-ED destination worsened by 0.61 (95% CI 0.33 to
      0.90) with diagnostic errors and by 0.60 (95% CI 0.30 to 0.90) with errors in
      follow up care. Patient dissatisfaction increased by 0.68 (95% CI 0.55 to 0.80)
      with information errors, by 0.63 (95% CI 0.17 to 1.09) with errors in follow up
      care, and by 0.52 (95% CI 0.09 to 0.94) with diagnostic errors. CONCLUSION:
      Unscheduled returns are associated with medical errors in prognosis, treatment,
      follow up care, and information. A worse post-ED destination is associated with
      these medical errors and patient factors (dyspnoea and advanced age). Patient
      dissatisfaction is associated with medical errors, level of triage or care zone,
      patient educational level and ED time work shift. Most of these factors are
      modifiable.

PMID- 16585112
TI  - Preventing drug related morbidity: a process for facilitating changes in
      practice.
AB  - AIM: To describe how quantitative data obtained from applying a series of
      indicators for preventable drug related morbidity (PDRM) in the electronic
      patient record in English general practice can be used to facilitate changes
      aimed at helping to improve medicines management. DESIGN: A multidisciplinary
      discussion forum held at each practice facilitated by a clinical researcher.
      SUBJECTS AND SETTING: Eight English general practices. OUTCOME MEASURES: Issues
      discussed at the multidisciplinary discussion forum and ideas generated by
      practices for tackling these issues. Progress made by practices after 1, 3, and 6
      months. RESULTS: A number of clinical issues were raised by the practices and
      ideas for moving them forward were discussed. The issues that were easiest and
      most straightforward to deal with (for example, reviewing specific patient
      groups) were quickly addressed in most instances. Practices were less likely to
      have taken steps towards addressing issues at a systems level. CONCLUSIONS: Data
      generated from applying PDRM indicators can be used to facilitate practice-wide
      discussion on medicines management. Different practices place different priority
      levels on the issues they wish to pursue. Individual practice "ownership" of
      these, together with having a central committed figure at the practice, is key to
      the success of the process.

PMID- 16585113
TI  - Reconcilable differences: correcting medication errors at hospital admission and
      discharge.
AB  - BACKGROUND: Medication errors at the time of hospital admission and discharge are
      common and can lead to preventable adverse drug events. The objective of this
      study was to describe the potential impact of a medication reconciliation process
      to identify and rectify medication errors at the time of hospital admission and
      discharge. METHODS: Sixty randomly selected patients were prospectively enrolled
      at the time of admission to a Canadian community hospital. At admission,
      patients' medication orders were compared with pre-admission medication use based
      on medication vials and interviews with patients, caregivers, and/or outpatient
      healthcare providers. At discharge, pre-admission and in-patient medications were
      compared with discharge orders and written instructions. All variances were
      discussed with the prescribing physician and classified as intended or
      unintended; unintended variances were considered to be medication errors. An
      internist classified the clinical importance of each unintended variance.
      RESULTS: Overall, 60% (95% CI 48 to 72) of patients had at least one unintended
      variance and 18% (95% CI 9 to 28) had at least one clinically important
      unintended variance. None of the variances had been detected by usual clinical
      practice before reconciliation was conducted. Of the 20 clinically important
      variances, 75% (95% CI 56 to 94) were intercepted by medication reconciliation
      before patients were harmed. DISCUSSION: Unintended medication variances at the
      time of hospital admission and discharge are common and clinically important. The
      medication reconciliation process identified and addressed most of these
      unintended variances before harm occurred. In this small study, medication
      reconciliation was a useful method for identifying and rectifying medication
      errors at times of transition. Reconciliation warrants broader evaluation.

PMID- 16585114
TI  - Treating the clock and not the patient: ambulance response times and risk.
AB  - BACKGROUND: In a qualitative study of paramedics' attitudes to pre-hospital
      thrombolysis (PHT), the government target that emergency calls should receive a
      response within 8 minutes emerged as a key factor influencing attitudes to staff
      morale and attitudes to the job as a whole. A study was undertaken to examine
      paramedics' accounts of the effects on patient care and on their own health and
      safety of attempts to meet the 8 minute target. METHODS: In-depth semi-structured
      interviews were conducted with a purposive sample of 20 experienced paramedics
      (16 men) mostly aged 30-50 years with a mean length of service of 19 years. The
      paramedics were encouraged to raise issues which they themselves considered
      salient. The interviews were tape recorded, transcribed, and analysed according
      to the constant comparative method. RESULTS: The paramedics argued that response
      time targets are inadequate as a performance indicator. They dominate ambulance
      service culture and practice at the expense of other quality indicators and are
      vulnerable to "fiddling". The targets can conflict with other quality indicators
      such as timely administration of PHT and rapid transport of patients to hospital.
      The strategies introduced to meet the targets can be detrimental to patient care
      and also have adverse effects on the health, safety, wellbeing, and morale of
      paramedics. CONCLUSIONS: The results of this study suggest that the 8 minute
      response time is not evidence based and is putting patients and ambulance crews
      at risk. There is a need for less simplistic quality indicators which recognise
      that there are many stages between a patient's call for help and safe arrival in
      hospital.

PMID- 16585115
TI  - Quality of diabetes care and coronary heart disease absolute risk in patients
      with type 2 diabetes mellitus in Australian general practice.
AB  - OBJECTIVE: To examine the quality of diabetes care and prevention of
      cardiovascular disease (CVD) in Australian general practice patients with type 2
      diabetes and to investigate its relationship with coronary heart disease absolute
      risk (CHDAR). METHODS: A total of 3286 patient records were extracted from
      registers of patients with type 2 diabetes held by 16 divisions of general
      practice (250 practices) across Australia for the year 2002. CHDAR was estimated
      using the United Kingdom Prospective Diabetes Study algorithm with higher CHDAR
      set at a 10 year risk of >15%. Multivariate multilevel logistic regression
      investigated the association between CHDAR and diabetes care. RESULTS: 47.9% of
      diabetic patient records had glycosylated haemoglobin (HbA1c) >7%, 87.6% had
      total cholesterol >or=4.0 mmol/l, and 73.8% had blood pressure (BP) >or=130/85 mm
      Hg. 57.6% of patients were at a higher CHDAR, 76.8% of whom were not on lipid
      modifying medication and 66.2% were not on antihypertensive medication. After
      adjusting for clustering at the general practice level and age, lipid modifying
      medication was negatively related to CHDAR (odds ratio (OR) 0.84) and total
      cholesterol. Antihypertensive medication was positively related to systolic BP
      but negatively related to CHDAR (OR 0.88). Referral to
      ophthalmologists/optometrists and attendance at other health professionals were
      not related to CHDAR. CONCLUSIONS: At the time of the study the diabetes and CVD
      preventive care in Australian general practice was suboptimal, even after a
      number of national initiatives. The Australian Pharmaceutical Benefits Scheme
      (PBS) guidelines need to be modified to improve CVD preventive care in patients
      with type 2 diabetes.

PMID- 16585116
TI  - Patient assessments of a hypothetical medical error: effects of health outcome,
      disclosure, and staff responsiveness.
AB  - OBJECTIVE: To assess whether patients' perceptions of a hypothetical medical
      error are influenced by staff responsiveness, disclosure of error, and health
      consequences of the error. DESIGN: Hypothetical scenario describing a medication
      error submitted by mail. Three factors were manipulated at random: rapid v slow
      staff responsiveness to error; disclosure v non-disclosure of the error; and
      occurrence of serious v minor health consequences. PARTICIPANTS: Patients
      discharged from hospital. MEASURES: Assessment of care described in the scenario
      as bad or very bad, rating of care as unsafe, and intent to not recommend the
      hospital. RESULTS: Of 1274 participants who evaluated the scenario, 71.4% rated
      health care as bad or very bad, 60.2% rated healthcare conditions as unsafe, and
      25.5% stated that they would not recommend the hospital. Rating health care as
      bad or very bad was associated with slow reaction to error (odds ratio (OR) 2.8,
      95% CI 2.1 to 3.6), non-disclosure of error (OR 2.0, 95% CI 1.5 to 2.6), and
      serious health consequences (OR 3.4, 95% CI 2.6 to 4.5). Similar associations
      were observed for rating healthcare conditions as unsafe and the intent to not
      recommend the hospital. Younger patients were more sensitive to non-disclosure
      than older patients. CONCLUSIONS: Former patients view medical errors less
      favorably when hospital staff react slowly, when the error is not disclosed to
      the patient, and when the patient suffers serious health consequences.

PMID- 16585117
TI  - Walter A Shewhart, 1924, and the Hawthorne factory.

PMID- 16585118
TI  - Making the case for more necropsies to improve patient care.

PMID- 16585119
TI  - What to do with outliers?

PMID- 16585120
TI  - Analysis of the overdispersed clock in the short-term evolution of hepatitis C
      virus: Using the E1/E2 gene sequences to infer infection dates in a single source
      outbreak.
AB  - The assumption of a molecular clock for dating events from sequence information
      is often frustrated by the presence of heterogeneity among evolutionary rates
      due, among other factors, to positively selected sites. In this work, our goal is
      to explore methods to estimate infection dates from sequence analysis. One such
      method, based on site stripping for clock detection, was proposed to unravel the
      clocklike molecular evolution in sequences showing high variability of
      evolutionary rates and in the presence of positive selection. Other alternatives
      imply accommodating heterogeneity in evolutionary rates at various levels,
      without eliminating any information from the data. Here we present the analysis
      of a data set of hepatitis C virus (HCV) sequences from 24 patients infected by a
      single individual with known dates of infection. We first used a simple criterion
      of relative substitution rate for site removal prior to a regression analysis.
      Time was regressed on maximum likelihood pairwise evolutionary distances between
      the sequences sampled from the source individual and infected patients. We show
      that it is indeed the fastest evolving sites that disturb the molecular clock and
      that these sites correspond to positively selected codons. The high computational
      efficiency of the regression analysis allowed us to compare the site-stripping
      scheme with random removal of sites. We demonstrate that removing the fast
      evolving sites significantly increases the accuracy of estimation of infection
      times based on a single substitution rate. However, the time-of-infection
      estimations improved substantially when a more sophisticated and computationally
      demanding Bayesian method was used. This method was used with the same data set
      but keeping all the sequence positions in the analysis. Consequently, despite the
      distortion introduced by positive selection on evolutionary rates, it is possible
      to obtain quite accurate estimates of infection dates, a result of especial
      relevance for molecular epidemiology studies.

PMID- 16585121
TI  - Misoprostol for cervical ripening in non-pregnant women: a randomized double
      blind controlled trial of oral versus vaginal regimens.
AB  - BACKGROUND: The objective was to compare the efficacy of oral versus vaginal
      misoprostol for cervical ripening in non-pregnant women. METHODS: Sixty non
      pregnant women scheduled for diagnostic hysteroscopy were randomized by
      computerized randomization schedule to 400 microg of misoprostol orally (n = 30)
      or 200 microg vaginally (n = 30) administered 12 h prior to surgery. The diameter
      of the cervical canal measured with a Hegar dilator, adverse events and any
      complications were recorded and compared between the two groups. RESULTS: The
      mean pre- and post-medication cervical canal diameter and cervical diameter
      difference were 2.00 +/- 1.93 versus 2.37 +/- 1.83 mm (P = 0.453), 5.10 +/- 1.75
      versus 5.60 +/- 1.69 mm (P = 0.265) and 3.10 +/- 1.79 versus 3.23 +/- 1.74 mm (P
      = 0.771) in the oral and vaginal group, respectively. Seven patients in the oral
      group and one patient in the vaginal group experienced diarrhoea within 24 h of
      administration of the misoprostol. CONCLUSION: Oral misoprostol 400 microg had
      similar efficacy in cervical ripening to 200 microg of vaginal misoprostol.

PMID- 16585122
TI  - Ovarian function and spontaneous pregnancy after combined heterotopic and
      orthotopic cryopreserved ovarian tissue transplantation in a patient previously
      treated with bone marrow transplantation: case report.
AB  - Cryopreservation of ovarian tissue has been proposed for storing gametes of young
      patients at high risk of premature ovarian failure. Autotransplantation has
      recently provided some promising results and is still the unique option to
      restore ovarian function from cryopreserved ovarian tissue in humans. In this
      article, we analyse data from the combined orthotopic and heterotopic
      transplantation of cryopreserved ovarian tissue that restored the ovarian
      function and fertility. Orthotopic transplantation of cryopreserved ovarian
      tissue at ovarian and peritoneal sites, together with a heterotopic
      transplantation at the abdominal subcutaneous site, was performed to restore the
      ovarian function of a 29-year-old woman previously treated with bone marrow
      transplantation (BMT) for Hodgkin's disease. Ovarian reserve markers
      progressively suppress within values 5 months after the transplantation (basal
      FSH 5 mUI/ml and inhibin B 119 ng/ml). Follicular development was observed at all
      transplantation sites but was predominant at the ovarian site. Six natural cycles
      were fully documented and analysed. The patient became spontaneously pregnant
      following the sixth cycle, but unfortunately she later miscarried. Combined
      orthotopic and heterotopic transplantations succeeded in the restoration of
      normal spontaneous cycles. Furthermore, this spontaneous pregnancy confirmed the
      efficiency of this procedure for restoring human fertility.

PMID- 16585123
TI  - Chromosome segregation in an infertile man carrying a unique pericentric
      inversion, inv(21)(p12q22.3), analysed using fluorescence in situ hybridization
      on sperm nuclei: significance for clinical genetics. A case report.
AB  - We report the case of a 40-year-old patient referred to our centre after 3 years
      of infertility. Karyotyping with the aid of fluorescence in situ hybridization
      (FISH) analysis showed a unique pericentric inversion of chromosome
      21:46,XY,inv(21)(p12q22.3). This type of intrachromosomal structural
      rearrangement can lead to chromosome imbalance in offspring by producing
      unbalanced gametes if an odd number of crossover events occur within the inverted
      segment. Therefore, partial trisomy/monosomy with clinical consequences can be
      observed in the progeny of carriers. Semen samples from the inversion carrier
      were analysed by FISH using a combination of probes [a subtelomeric 21q probe and
      a locus-specific Down's syndrome critical region (DSCR) probe] to evaluate the
      proportion of recombinant chromosomes. Sperm-FISH analysis of 3400 spermatozoa
      revealed a 67.4% rate of balanced chromosomes (normal or inverted). The
      frequencies of recombinant chromosomes with duplication of the long arm and
      deletion of the short arm, and vice versa, were 11.2 and 21.4%, respectively. The
      risk for the couple of conceiving a child with an unbalanced chromosome 21 is
      estimated to be around 32%. This case study shows the utility of sperm-FISH
      analysis in the genetic counselling of a pericentric inversion in a male carrier
      to assess the frequency of recombinant chromosomes and therefore evaluate the
      probability of having a normal conception.

PMID- 16585124
TI  - Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-alpha in
      menstrual endometrium and effluent in women with menorrhagia.
AB  - BACKGROUND: Heavy regular menstrual periods (menorrhagia) are an important cause
      of ill health in women and remain the leading indication for hysterectomy.
      Abnormalities of the endometrial blood vessels are among the possible causes of
      this condition. Many different factors affect endothelial cell growth, function
      and vessel remodelling. We sought to determine whether the levels of vascular
      endothelial growth factor-A (VEGF-A), tumour necrosis factor-alpha (TNF-alpha),
      matrix metalloproteinase (MMP)-2 and MMP-9 and soluble VEGF receptor-1 (VEGF-R1)
      were altered in the menstrual effluent of women with objective menorrhagia. We
      have also quantitated the VEGF-A mRNA in the menstruated endometrium. METHODS AND
      RESULTS: We recruited 37 women and determined their menstrual blood loss (MBL)
      over two cycles and collected menstrual effluent during the 2nd day of bleeding
      for 4 h. There was no difference in the total level of VEGF-A, and neither latent
      MMP. However, the concentration of VEGF-A was significantly reduced in the women
      with menorrhagia, as was the VEGF-A mRNA level. In addition, the active forms of
      both MMPs were markedly reduced and the total sVEGF-R1 as well as the TNF-alpha
      content were increased. CONCLUSIONS: This is the first study to show
      abnormalities of factors important for endothelial cell behaviour in the
      endometrium of women with menorrhagia. This may underlie the disordered vessel
      structure and/or function in this condition.

PMID- 16585125
TI  - A cost-utility analysis of hysterectomy, endometrial resection and ablation and
      medical therapy for menorrhagia.
AB  - BACKGROUND: Four types of treatment [hysterectomy, endometrial
      resection/ablation, levonorgestrel-releasing intrauterine system (LNG-IUS) and
      oral medical therapy] are available for management of menorrhagia. The objective
      of this study was to compare the cost and quality-adjusted life-years (QALYs)
      gained by these four treatment alternatives. METHODS: A Markov model was designed
      to simulate the healthcare resource utilization and QALYs of the four treatment
      alternatives for patients presenting with menorrhagia over 5 years. Clinical
      inputs were estimated from literature, and the cost analysis was conducted from
      the perspective of healthcare provider in Hong Kong. RESULTS: The base-case
      analysis showed that the hysterectomy group was the most effective (4.725 QALYs)
      alternative with the highest cost (USD6878, 1USD=7.8HKD). The incremental cost
      per additional QALY (ICER) gained by hysterectomy was USD23 500. The probability
      of extra surgery in the endometrial resection/ablation was an influential factor.
      Probabalistic sensitivity analysis of 10,000 simulations of the Monte Carlo model
      showed that the hysterectomy group gained higher number of QALYs than the LNG
      IUS, oral medical treatment and endometrial resection/ablation groups, 99, 99 and
      98% of the time, and it was more costly than the other three groups over 85% of
      the time. CONCLUSIONS: Hysterectomy appears to be cost effective, with ICER less
      than USD50,000, for management of menorrhagia.

PMID- 16585126
TI  - Assisted reproductive technology in Europe, 2002. Results generated from European
      registers by ESHRE.
AB  - European results of assisted reproductive techniques (ART) from treatments
      initiated during 2002 are presented in this sixth report. Data was mainly
      collected from already existing national registers. From 25 countries, 631
      clinics reported 324,238 treatment cycles with: IVF 122,634, ICSI 135,048, frozen
      embryo replacement (FER) 57 162, egg donation (ED) 7677, preimplantation genetic
      diagnosis/screening (PGD/PGS) 1563 and in vitro maturation (IVM) 154. Overall
      this represents a 12% increase since year 2001. For the second time, results on
      European data on intrauterine inseminations were reported from 17 countries. A
      total of 93,284 cycles [IUI-husband/partner (H), 78 505 and IUI-donor (D),
      14,779] were included. In 13 countries where all clinics reported to the
      register, a total of 177,429 cycles were performed in a population of 193.7
      million, corresponding to 916 cycles per million inhabitants. For IVF the
      clinical pregnancy rate per aspiration and per transfer was 26.0 and 29.5%,
      respectively. For ICSI the corresponding rates were 27.2 and 29.4%. These figures
      are marginally better than in 2001. After IUI-H the clinical pregnancy rate was
      11.6% in women below 40 and 7.8% in women>or=40 years of age. After IVF and ICSI
      the distribution of transfer of 1, 2, 3 and 4 or more embryos was 13.7, 54.8,
      26.9 and 4.7%, respectively. Compared with year 2001, less embryos were
      transferred, but huge differences existed between countries. The distribution of
      singleton, twin and triplet deliveries for IVF and ICSI combined was 75.5, 23.2
      and 1.3%, respectively. This gives a total multiple delivery rate of 24.5%,
      compared with 25.5% in year 2001. The range of triplet deliveries after IVF and
      ICSI varied from 0.0 to 5.2% between countries. After IUI-H in women below 40
      years of age, 10.2% were twin and 1.3% triplet gestations.

PMID- 16585127
TI  - Death receptor and mitochondrial pathways are involved in germ cell apoptosis in
      an experimental model of autoimmune orchitis.
AB  - BACKGROUND: Studies on experimental autoimmune orchitis (EAO) have helped to
      elucidate immunological mechanisms involved in testicular damage. We previously
      demonstrated that EAO is characterized by lymphomononuclear cell infiltrates and
      apoptosis of spermatocytes and spermatids expressing Fas and TNFR1. The aim of
      this work was to characterize the pathways involved in germ cell apoptosis in EAO
      and to determine the involvement of the Bcl-2 protein family in this process.
      METHODS AND RESULTS: EAO was induced in rats by immunization with testicular
      homogenate (TH) and adjuvants, whereas control (C) rats were injected with saline
      solution and adjuvants. Testis of EAO rats showed procaspase 8 cleavage products
      (western blot) with high caspase 8 activity. Cytochrome c content increased in
      the cytosol and decreased in the mitochondrial fraction of testis from EAO rats
      compared with C, concomitant with increased caspase 9 activity. Bax was mainly
      expressed in spermatocytes and spermatids and Bcl-2 in basal germ cells
      (immunohistochemistry). Baxbeta isoform content increased in EAO rat testis
      compared with C, whereas content of Baxalpha remained unchanged (western blot).
      However, Baxalpha content decreased in the cytosol and increased in the
      mitochondrial and endoplasmic reticulum (ER)-enriched fractions of testis from
      EAO rats compared with C (western blot). Bcl-2 content also increased in the
      testes of EAO rats. CONCLUSIONS: Our results demonstrated that extrinsic,
      mitochondrial and possibly ER pathways are inducers of germ cell apoptosis in EAO
      and that Bax and Bcl-2 proteins modulate this process.

PMID- 16585128
TI  - Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a
      systematic review of randomized controlled trials.
AB  - BACKGROUND: Vitamin B(12) deficiency is common, increasing with age. Most people
      are treated in primary care with intramuscular vitamin B(12). Several studies
      have reported equal efficacy of oral administration of vitamin B(12). OBJECTIVES:
      We set out to identify randomized controlled trial (RCT) evidence for the
      effectiveness of oral versus intramuscular vitamin B(12) to treat vitamin B(12)
      deficiency. METHODS: We conducted a systematic review searching databases for
      relevant RCTs. Outcomes included levels of serum vitamin B(12), total serum
      homocysteine and methylmalonic acid, haemoglobin and signs and symptoms of
      vitamin B(12) deficiency. RESULTS: Two RCTs comparing oral with intramuscular
      administration of vitamin B(12) met our inclusion criteria. The trials recruited
      a total of 108 participants and followed up 93 of these from 90 days to 4 months.
      In one of the studies, mean serum vitamin B(12) levels were significantly higher
      in the oral (643 +/- 328 pg/ml; n = 18) compared with the intramuscular group
      (306 +/- 118 pg/ml; n = 15) at 2 months (P < 0.001) and 4 months (1005 +/- 595
      versus 325 +/- 165 pg/ml; P < 0.0005) and both groups had neurological responses.
      In the other study, serum vitamin B(12) levels increased significantly in those
      receiving oral vitamin B(12) and intramuscular vitamin B(12) (P < 0.001).
      CONCLUSIONS: The evidence derived from these limited studies suggests that 2000
      microg doses of oral vitamin B(12) daily and 1000 microg doses initially daily
      and thereafter weekly and then monthly may be as effective as intramuscular
      administration in obtaining short-term haematological and neurological responses
      in vitamin B(12)-deficient patients.

PMID- 16585129
TI  - A cross-sectional study of secondary cardiac care in general practice: impact of
      personal and practice characteristics.
AB  - OBJECTIVE: To determine the impact of patient (age, gender, type of and time
      since diagnosis) and practice (rurality, number of partners, availability of
      practice nurse) characteristics on secondary cardiac care in general practice in
      a country without universal registration. METHODS: Medical and demographic data
      were gathered from the medical charts of 1611 eligible patients from 35 randomly
      selected practices. Eligible patients were aged under 80 years with a recorded
      history of acute myocardial infarction, percutaneous trans coronary arteriogram
      or angina. Self-report data about diet, exercise, smoking and alcohol consumption
      were provided from postal questionnaire (1084 patients responded; 69% response
      rate). RESULTS: Having an angina only diagnosis significantly decreased the
      likelihood of patients being prescribed aspirin (OR = 0.53; 95% CI = 0.40-0.69),
      lipid-lowering medication (OR = 0.55; 95% CI = 0.43-0.69) or ACE inhibitors (OR =
      0.62; 95% CI = 0.48-0.81). Younger patients (OR = 1.05; 95% CI = 1.04-1.06) were
      also more likely to be prescribed lipid-lowering medication. Cholesterol was
      predicted by gender only, with females having significantly higher cholesterol (B
      = -0.41; 95% CI = -0.54 to -0.27). The number of missed opportunities for
      secondary cardiac care was greater among patients with angina only (B = 0.39; 95%
      CI = 0.19-0.60). The amount of variance explained by practice and patient
      variables overall for each of the measures was small, ranging from 2 to 6%.
      CONCLUSIONS: Practice size or location appears to have little impact on secondary
      cardiac care. The most consistent significant personal characteristic finding was
      that patients with a diagnosis of angina only were significantly less likely to
      receive aspirin, statins or ACE inhibitors and more likely to have more missed
      opportunities for secondary cardiac care.

PMID- 16585132
TI  - An evaluation of the Health Promoting Health Service Framework: the
      implementation of a settings based approach within the NHS in Scotland.
AB  - In 1996 the Health Education Board for Scotland (now NHS Health Scotland) began a
      process of developing a 'settings'-based framework that would inform health
      promotion work across Scottish health services--the Health Promoting Health
      Service Framework (HPHS). It took the form of a flexible guidance document,
      attending to the foundations of integrated and sustainable health promotion
      practice via specific areas like partnership work, policy development and staff
      health. The project has subsequently been progressed over an extended period,
      comprising three phases: an initial development of the resource; piloting of the
      framework; and a wider assessment of implementation and initial impact. This
      paper reports on the latter phase. Within the context of various issues
      pertaining to the evaluation of a 'settings' approach and based on the use of
      case study methodology in nine HPHS pilot sites, this paper reports on the latter
      2 year phase. This involved ongoing concern for understanding intervention
      processes and a growing interest in intervention outcomes and the paper reports
      on findings in each of these domains. In relation to outcomes, some positive
      gains in various indicators were detected though significant problems were
      experienced in this aspect. More significantly, the work was able to gain
      insights into what we call 'necessary conditions' of implementation. We theorize
      a range of 'contextual' factors (e.g. responsiveness to health improvement policy
      agendas) and project specific 'mechanisms' (e.g. providing skilled support) and
      present these as a nexus of conditions required for effective implementation of
      health promotion practice within explanatory models. Most significantly, we
      stress the relative frailty of any settings implementation strategy based simply
      on the uncoordinated dissemination of a tool or resource.

PMID- 16585130
TI  - Tea polyphenol epigallocatechin-3-gallate inhibits ergosterol synthesis by
      disturbing folic acid metabolism in Candida albicans.
AB  - OBJECTIVES: Elucidation of the mechanism of action of epigallocatechin-3-gallate
      (EGCG) against Candida albicans and demonstration of the connection between its
      antifolate activity and other metabolic pathways involved in C. albicans survival
      are the major objectives of this study. METHODS: C. albicans ATCC 10231 and 12
      clinical isolates were used. MICs of EGCG against C. albicans were determined
      according to NCCLS. C. albicans dihydrofolate reductase (DHFR) was purified using
      methotrexate-affinity chromatography and its inhibition by EGCG studied by
      spectroscopic techniques. Synergy experiments were performed by chequerboard
      tests by combining eight doubling concentrations of EGCG with another eight
      dilutions of azole compounds or terbinafine. Reversion experiments with
      leucovorin or S-adenosylmethionine were carried out, and the content of
      ergosterol was determined by a spectrophotometric method. RESULTS: EGCG is an
      efficient inhibitor of C. albicans DHFR (K(i) = 0.7 microM). As with other
      antifolates, the effects of EGCG on C. albicans can be highly attenuated by
      growing the cells in the presence of leucovorin. EGCG showed synergy with
      inhibitors of the ergosterol biosynthesis pathway in C. albicans such as azole
      antifungals and terbinafine. We demonstrate that by disturbing the folate
      metabolism, EGCG can inhibit ergosterol production. The molecular connection
      between the pathways is discussed. CONCLUSIONS: EGCG acts as an antifolate
      compound on C. albicans, disturbing its folic acid metabolism. This effect could
      explain the molecular mechanism for the synergy between EGCG and azole
      antifungals, and could represent a starting point for therapies involving
      antifolates and azoles used as an alternative for the treatment of C. albicans
      infections.

PMID- 16585131
TI  - Fluoroquinolone resistance and plasmid addiction systems: self-imposed selection
      pressure?
AB  - Multi-antibiotic-resistant Gram-negative pathogens are becoming more prevalent
      and an association exists between chromosomally conferred fluoroquinolone
      resistance and the presence of plasmid-borne resistances, such as extended
      spectrum beta-lactamases. This link is not wholly explained by strain spread or
      the presence of fluoroquinolone-modifying enzymes. Plasmid-encoded toxin
      antitoxin addiction systems enforce plasmid maintenance in bacteria and, like
      fluoroquinolones, some toxins target DNA gyrase. Bacteria can develop resistance
      to these toxins, which would free the cell of the plasmid addiction and allow it
      to ditch the "excess baggage". We hypothesize that these plasmid-encoded gyrase
      toxins might contribute to, or predispose towards, clinically significant
      fluoroquinolone resistance, and that the plasmid-encoded quinolone resistance
      determinant, Qnr, may facilitate this. Establishing the extent and mechanisms of
      cross-resistance to toxins and fluoroquinolones will aid the management of
      resistance and may contribute to the development of novel antimicrobials.

PMID- 16585133
TI  - Association between cigarette smoking and release of tumour necrosis factor alpha
      and its soluble receptors by peripheral blood mononuclear cells in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the relationship between cigarette smoking and release
      of TNF-alpha and its soluble receptors (sTNFRI and sTNFRII) by peripheral blood
      mononuclear cells (PBMCs) from RA patients. METHODS: We studied 71 RA patients
      with established disease (mean duration 10.6 yr). Smoking history was established
      by questionnaire. T lymphocytes and monocytes were isolated from peripheral blood
      and incubated with or without stimulation (phytohaemagglutinin and
      lipopolysaccharide, respectively). Release of TNF-alpha and sTNFR into culture
      medium was measured by enzyme-linked immunosorbent assay. RESULTS: TNF-alpha
      release by stimulated T lymphocytes was significantly higher in patients with a
      history of smoking than in those who had never smoked (1416.0 vs 767.4 pg/ml, P =
      0.04), and showed a relationship with smoking duration and intensity (P for trend
      < or =0.009). Monocyte TNF-alpha release was not associated with smoking status.
      Release of sTNFR showed no clear relationships with extent of smoking, although
      release by stimulated T lymphocytes was higher in past smokers than in those who
      had never smoked (P < or = 0.03). The ratio of TNF-alpha/sTNFR released from T
      lymphocytes was higher in past and current smokers, and was associated with
      extent of smoking. No relationship was found between smoking and plasma TNF-alpha
      levels, but levels of both receptors were higher in past smokers. CONCLUSION: In
      RA patients who smoke there is an alteration in the ratio of TNF-alpha/sTNFR
      released by stimulated T cells that might favour increased TNF-alpha activity.
      The increased TNF-alpha/sTNFR ratio is associated with extent of smoking, and
      remains elevated after smoking cessation.

PMID- 16585134
TI  - Significant expansion of Vicia pannonica genome size mediated by amplification of
      a single type of giant retroelement.
AB  - Amplification and eventual elimination of dispersed repeats, especially those of
      the retroelement origin, account for most of the profound size variability
      observed among plant genomes. In most higher plants investigated so far,
      differential accumulation of various families of elements contributes to these
      differences. Here we report the identification of giant Ty3/gypsy-like
      retrotransposons from the legume plant Vicia pannonica, which alone make up
      approximately 38% of the genome of this species. These retrotransposons have
      structural features of the Ogre elements previously identified in the genomes of
      pea and Medicago. These features include extreme size (25 kb), the presence of an
      extra ORF upstream of the gag-pol region, and a putative intron dividing the prot
      and rt coding sequences. The Ogre elements are evenly dispersed on V. pannonica
      chromosomes except for terminal regions containing satellite repeats, their
      individual copies show extraordinary sequence similarity, and at least part of
      them are transcriptionally active, which suggests their recent amplification.
      Similar elements were also detected in several other Vicia species but in most
      cases in significantly lower numbers. However, there was no obvious correlation
      of the abundance of Ogre sequences with the genome size of these species.

PMID- 16585135
TI  - Multiple-interval mapping for ordinal traits.
AB  - Many statistical methods have been developed to map multiple quantitative trait
      loci (QTL) in experimental cross populations. Among these methods, multiple
      interval mapping (MIM) can map QTL with epistasis simultaneously. However, the
      previous implementation of MIM is for continuously distributed traits. In this
      study we extend MIM to ordinal traits on the basis of a threshold model. The
      method inherits the properties and advantages of MIM and can fit a model of
      multiple QTL effects and epistasis on the underlying liability score. We study a
      number of statistical issues associated with the method, such as the efficiency
      and stability of maximization and model selection. We also use computer
      simulation to study the performance of the method and compare it to other
      alternative approaches. The method has been implemented in QTL Cartographer to
      facilitate its general usage for QTL mapping data analysis on binary and ordinal
      traits.

PMID- 16585136
TI  - N-Glycosylation of the MUC1 mucin in epithelial cells and secretions.
AB  - The MUC1 mucin is an important tumor-associated antigen that shows extensive
      glycosylation in vivo. The O-glycosylation of this molecule, which has been well
      characterized in many cell types and tissues, is important in conferring the
      unusual biochemical and biophysical properties on a mucin. N-Glycosylation is
      crucial to the folding, sorting, membrane trafficking, and secretion of many
      proteins. Here, we evaluated the N-glycosylation of MUC1 derived from two
      sources: endogenous MUC1 isolated from human milk and a recombinant epitope
      tagged MUC1F overexpressed in Caco2 colon carcinoma cells. N-Glycans on purified
      MUC1F/MUC1 were analyzed by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF-MS), gas chromatography-mass spectrometry (GC
      MS), and CAD-ESI-MS/MS. The spectra indicate that MUC1F N-glycans have
      compositions consistent with high-mannose structures (Hex(5-9)HexNAc(2)) and
      complex/hybrid-type glycans (NeuAc(0-3)Fuc(0-3)Hex(3-8)HexNAc(3-7)). Many of the
      N-glycan structures are identical on MUC1F and native MUC1; however, a marked
      difference is seen between the N-glycans on membrane-bound and secreted forms of
      the native molecule.

PMID- 16585138
TI  - Creative partnerships for community health improvement: a qualitative evaluation
      of the Healthy Carolinians community micro-grant project.
AB  - This qualitative study evaluated a recent innovative strategy used to involve
      community-based organizations (CBOs) in implementing health-related projects
      through locally administered microgrants. The purpose of this study was to
      identify key elements that enabled the success of the CBO projects, barriers and
      challenges to project success, and ways to effectively engage CBOs as partners in
      local health initiatives. In addition, this study sought to identify aspects of
      this approach that can be replicated. Study findings revealed that microfinancing
      CBOs aided in building partnerships, developing local leadership and expertise,
      and providing resources that enabled progress toward CBO missions and goals.
      These positive outcomes far out-weighed barriers and challenges faced by CBOs.
      Furthermore, the results of this study revealed ideas and information that
      provide useful guidelines for establishing and administering microgrant projects
      through local organizations that encourage community groups to design and
      implement community based health initiatives.

PMID- 16585140
TI  - All or nothing... or just a hat? Farmers' sun protection behaviors.
AB  - Farmers have an increased risk for developing skin cancers and thus comprise an
      important audience for messages that address sun protection practices. This
      project examines sun protection behaviors of farmers from southeastern Georgia
      and uses those measured behaviors to conduct a cluster analysis. Farmers (N =
      480) were clustered into three groups using six variables that measured their
      frequency of sun protective and purchasing behaviors. The three groups were
      characterized as either engaging heavily in sun protective behaviors, engaging in
      none of the recommended sun protective behaviors, or only wearing hats as a sun
      protective behavior. Practitioners seeking to develop health message
      interventions that target farming populations should consider the current
      behaviors of subgroups of farmers when developing audience segments to tailor
      messages aimed at increasing sun protective behaviors. Practical recommendations
      for message content targeted toward the subgroups of farmers are provided.

PMID- 16585139
TI  - Girl World: a primary prevention program for Mexican American girls.
AB  - Theories about women's health have not traditionally been extended to include the
      healthy development of young women. This article applies a women's health
      perspective to the implementation and evaluation processes of a gender-specific
      primary prevention program that worked with 9- to 14-year-old Hispanic girls in a
      low-income community. Although community-based after-school programs can be an
      important venue for education and girls' development, long-term effects are
      elusive to evaluate. The authors used ethnographic techniques to learn more about
      girls and their interactions with the program and to assess short-term program
      impact. Three themes were found: Program environment can contribute to girls'
      expression and behavior, issues of struggling families can slide girls into early
      adulthood, and mentoring can benefit both girls and adult women. Community-based
      primary prevention programs, although an essential part of a social safety net
      available to low-income girls, provide researchers with a unique set of
      evaluation challenges.

PMID- 16585141
TI  - Using the PRECEDE model to plan men's health programs in a managed care setting.
AB  - Managed care organizations represent an important venue for delivering health
      promotion programs. However, most health plans do not employ public health
      strategies that match peoples' needs and preferences to effective behavior change
      techniques. This article focuses on the planning efforts by Blue Cross and Blue
      Shield of North Carolina (BCBSNC) to address the problem of underutilization of
      preventive health care services among adult male members--an issue that has
      received comparatively little attention in the health behavior arena. BCBSNC
      planners used the PRECEDE planning process to define issues relevant to the
      target population and determine appropriate intervention strategies. Increasing
      perceived susceptibility and severity to disease, perceived benefits of
      screening, physician recommendation for screening, and health knowledge/awareness
      emerged as intervention priorities. The PRECEDE planning process yielded
      important evidence-based information and strategies to address men's underuse of
      preventive services and led BCBSNC to adopt new systems for planning
      interventions to promote the health of its members.

PMID- 16585142
TI  - Examining the perspectives of Texas minors cited for possession of tobacco.
AB  - This study examined the personal experiences of twenty 14-to-19-year-old Texas
      youth cited for tobacco possession and attending a court-mandated tobacco
      awareness class. Guided by labeling theory, focus group questions addressed the
      process of citation, how youth viewed themselves following citation, how parents
      and peers viewed youth following citation, and youths' views on the purpose and
      effects of the policy. Many youth felt stupid for being caught or determined that
      they were unlucky. Parents were upset that youth were caught smoking; however,
      most knew their children smoked. Peers felt sympathy for cited youth or made fun
      of them for being caught. Participants felt that the law was in existence to
      deter younger children from initiating smoking or to encourage older minors to
      quit smoking. However, youth also indicated that there was no purpose to the law
      and that instead of decreasing smoking it could lead to its continuation.
      Implications for practice are discussed.

PMID- 16585143
TI  - Marketing social marketing: getting inside those "big dogs' heads" and other
      challenges.
AB  - Social marketing provides a powerful process for planning and implementing public
      health programs. Although often applied to the promotion of healthier lifestyles,
      social marketing can also be used to promote utilization of direct services or
      policy changes. Despite growing popularity among public health professionals,
      resistance by senior management, community advocates, policy makers, and others
      can create barriers to the use of the social marketing model. This article draws
      on the authors' observations, practice experiences, extensive training
      interactions, and qualitative studies with public health practitioners across the
      nation. It examines some of the key reasons that public health practitioners
      encounter resistance to using social marketing and discusses how a logic model
      can be used to market social marketing in organizations and communities.

PMID- 16585144
TI  - Demographic and past screening behaviors of men attending a free community
      screening program for prostate cancer.
AB  - This study characterizes demographic and past prostate screening behaviors of men
      who participated in a free screening for prostate cancer. Demographics, past
      prostate screening behavior, perceived risk, and cancer worry were assessed in
      1,680 men. Mean age was 58.2 years, 56% were White, and 76% had health insurance.
      Men with insurance were more likely to have had a previous prostate-specific
      antigen (PSA) test and digital rectal exam (DRE). White men were more likely to
      have had a previous PSA and DRE and to have discussed PSA testing with a
      physician than African American men. African American men reported greater
      perceived risk and more worry than White men. Screening differences between
      African American and White men were explained by insurance status. These results
      may help guide the development of and promotion for future screening programs.
      Future efforts should be directed at increasing awareness about screening
      procedures for prostate cancer.

PMID- 16585145
TI  - Out of the mainstream: low-income, lone mothers' life experiences and
      perspectives on heart health.
AB  - Cardiovascular disease remains a health issue in North America, particularly for
      marginalized citizens. Although lifestyle issues and behavioral risk reduction
      continue to dominate prevention initiatives, an emerging literature suggests that
      contextual factors such as poverty and social exclusion also influence health.
      Using group and personal interviews (N = 38), this research explored the social
      and economic contexts shaping heart health-related experiences from the
      perspectives of low-income, lone mothers. The transcripts were analyzed using
      McKinlay and Marceau's upstream-midstream-downstream framework. The overriding
      pattern characterizing lone mothers' discussions was that the women felt out of
      the mainstream of everyday life. They lacked the resources and power to effect
      change, particularly regarding heart health behaviors that were not perceived to
      be a priority compared to more pressing survival issues. Results are discussed in
      terms of concepts from the population health and social determinants literature,
      concluding with policy implications for enhancing health while living in poverty.

PMID- 16585146
TI  - Application of qualitative methods in program planning for health promotion
      interventions.
AB  - The use of qualitative methods can provide an in-depth understanding of the
      issues and barriers related to community health and can help to inform the
      planning of health promotion programs and interventions. Although there are many
      examples in the literature that describe the application of quantitative data to
      program planning, few articles explicitly describe the application of qualitative
      data, such as data gathered using focus groups, in-depth interviews, and
      windshield tours, in program planning. Using the East Side Village Health Worker
      Partnership in Detroit, Michigan, as a case study example, this article explains
      the methods of incorporating qualitative data into each stage of program planning
      and development, including community assessment, development of goals and
      objectives, implementation of activities, and program evaluation.

PMID- 16585147
TI  - A blueprint for assessing public support of citywide smoke-free legislation.
AB  - The tracking of public opinion can be a critical component of antitobacco
      campaigns, such as efforts to enact citywide Clean Indoor Air legislation.
      Grassroots tobacco control coalitions that work locally to promote smoke-free
      environments typically encompass individuals from a wide range of public health
      fields. Although knowledgeable, volunteer groups lack the financial resources to
      evaluate the impact of local efforts or determine their community's level of
      support for potential legislation. The steps taken by a grassroots organization
      to conduct a public opinion survey are outlined, including methodological,
      analytical issues, and resource requirements. A valid survey can be completed in
      4 months with minimal financial resources. Individuals willing to voluntarily
      administer and analyze a survey can be identified at the local level. Results of
      a tobacco-related public opinion survey can be instrumental in the promotion of
      smoke-free environments and an effective tool in attracting media coverage.

PMID- 16585148
TI  - Cookin' Up Health: developing a nutrition intervention for a rural Appalachian
      population.
AB  - Cookin' Up Health is a culturally targeted and individualized tailored nutrition
      intervention using a computer-based interactive format. Using a cooking show
      theme, the program demonstrates step-by-step meal preparation emphasizing healthy
      selection and portion control. Focus groups were conducted with women in two
      rural counties in West Virginia to guide the development of the intervention.
      Women felt more susceptible to heart disease because the changing role of women
      creates more stress and less time; weight loss was a greater motivator for
      dietary change than was preventing heart disease; social support is a barrier and
      facilitator for dietary change; cultural heritage and the way women were raised
      were major barriers to making health changes as adults; convenience and the cost
      of eating healthier were major factors when trying to make changes in diet; and
      women did not feel confident in their ability to maintain dietary changes.

PMID- 16585149
TI  - Survey of accredited master of public health (MPH) programs with health education
      concentrations: a resource for strengthening the public health workforce.
AB  - The authors designed survey research to assess accredited master of public health
      (MPH) programs with health education concentrations. A Web-based survey was
      distributed to program directors and was used to collect characteristics of
      program faculty, students, graduates, internships, employment, and competency
      development. Results indicate that students and graduates are diverse; 72% of
      students complete internships and 61% of graduates work in government or
      community public health-related agencies; 98% of faculty hold a doctoral degree
      and 67% have at least one degree from an accredited public health school or
      program; and 85% of programs build competencies in most of the Institute of
      Medicine-suggested areas. The authors conclude that accredited MPH programs with
      a concentration in health education train diverse public health practitioners
      highly likely to work in a government or community public health agency with
      competencies to enhance public health.

PMID- 16585150
TI  - Using chemopreventive agents to enhance the efficacy of cancer therapy.
AB  - Emerging evidence suggests that cancer preventative agents might be combined with
      chemotherapy or radiotherapy for the more effective treatment of cancer. Recent
      studies suggest that genistein and other dietary compounds that prevent cancer
      may enhance the efficacy of cancer therapeutics by modifying the activity of key
      cell proliferation and survival pathways, such as those controlled by Akt,
      nuclear factor-kappaB, and cyclooxygenase-2. In this article, we summarize the
      findings of recent investigations of chemopreventive agents in combination with
      cancer treatment regimens.

PMID- 16585151
TI  - Contributions of human tumor xenografts to anticancer drug development.
AB  - Mouse models of cancer have consistently been used to qualify new anticancer
      drugs for study in human clinical trials. The most used models include
      transplantable murine tumors grown in syngeneic hosts and xenografts of human
      tumors grown in immunodeficient mice. For the latter systems, retrospective
      preclinical-clinical correlation studies are available, which suggest that
      improvements must be made to increase their value. Transgenic, knock-out, and
      knock-in mouse models and their intercrosses are more recent developments that
      mirror defined steps of human carcinogenesis. However, their value in predicting
      clinical results remains to date poorly defined. We take the position that
      properly used and interpreted human tumor xenografts grown in immunodeficient
      mice can be useful, although not absolutely predictive of behavior in the clinic,
      and continue to make contributions to critical clinical development choices.

PMID- 16585152
TI  - Genetically engineered models have advantages over xenografts for preclinical
      studies.
AB  - Mouse models of human cancer are valuable tools for cancer research. Although
      xenografts and genetically engineered models (GEMs) possess limitations as well
      as advantages, each system plays a significant role in preclinical testing. Tumor
      xenografts are easy to use, relatively inexpensive, and reproducible. The main
      drawback of xenografts is that the genetics and histology of the tumors are
      frequently not representative of the respective human tumor and, thus far, these
      models have not been as predictive of therapeutic success as one would like. By
      contrast, GEMs are histologically and genetically accurate models of human cancer
      but have disadvantages of heterogeneity with regard to frequency, latency, and
      growth. These disadvantages are reminiscent of the variable behavior of actual
      human tumors. Recently, these shortcomings have been partly overcome with the
      development of anatomic and molecular in vivo imaging techniques such as magnetic
      resonance imaging and bioluminescence imaging. These new technologies will
      hopefully support the use of GEMs in preclinical trials and help determine if
      trials in GEMs are more predicative than xenografts of human responses.

PMID- 16585153
TI  - Onset of abnormal blood and lymphatic vessel function and interstitial
      hypertension in early stages of carcinogenesis.
AB  - Recent improvements in diagnostic methods have opened avenues for detection and
      treatment of (pre)malignant lesions at early stages. However, due to the lack of
      spontaneous tumor models that both mimic human carcinogenesis and allow direct
      optical imaging of the vasculature, little is known about the function of blood
      and lymphatic vessels during the early stages of cancer development. Here, we
      used a spontaneous carcinogenesis model in the skin of DNA polymerase eta
      deficient mice and found that interstitial fluid pressure was already elevated in
      the hyperplastic/dysplastic stage. This was accompanied by angiogenic blood
      vasculature that exhibited altered permeability, vessel compression, and
      decreased alpha-smooth muscle actin-positive perivascular cell coverage. In
      addition, the lymphatic vessels in hyperplastic/dysplastic lesions were partly
      compressed and nonfunctional. These novel insights may aid early detection and
      treatment strategies for cancer.

PMID- 16585155
TI  - Prediction of sensitivity of rectal cancer cells in response to preoperative
      radiotherapy by DNA microarray analysis of gene expression profiles.
AB  - Preoperative radiotherapy has been widely used to improve local control of
      disease and to improve survival in the treatment of rectal cancer. However, the
      response to radiotherapy differs among individual tumors. Our objective here was
      to identify a set of discriminating genes that can be used for characterization
      and prediction of response to radiotherapy in rectal cancer. Fifty-two rectal
      cancer patients who underwent preoperative radiotherapy were studied. Biopsy
      specimens were obtained from rectal cancer before preoperative radiotherapy.
      Response to radiotherapy was determined by histopathologic examination of
      surgically resected specimens and classified as responders or nonresponders. By
      determining gene expression profiles using human U95Av2 Gene Chip, we identified
      33 novel discriminating genes of which the expression differed significantly
      between responders and nonresponders. Using this gene set, we were able to
      establish a new model to predict response to radiotherapy in rectal cancer with
      an accuracy of 82.4%. The list of discriminating genes included growth factor,
      apoptosis, cell proliferation, signal transduction, or cell adhesion-related
      genes. Among 33 discriminating genes, apoptosis inducers (lumican, thrombospondin
      2, and galectin-1) showed higher expression in responders whereas apoptosis
      inhibitors (cyclophilin 40 and glutathione peroxidase) showed higher expression
      in nonresponders. The present study suggested the possibility that gene
      expression profiling may be useful in predicting response to radiotherapy to
      establish an individualized tailored therapy for rectal cancer. Global expression
      profiles of responders and nonresponders may provide insights into the
      development of novel therapeutic targets.

PMID- 16585154
TI  - N-cadherin gene expression in prostate carcinoma is modulated by integrin
      dependent nuclear translocation of Twist1.
AB  - The gain of N-cadherin expression in carcinomas has been shown to be important in
      the regulation of cell migration, invasion, and survival. Here, we show that N
      cadherin mRNA expression in PC-3 prostate carcinoma cells is dependent on beta(1)
      integrin-mediated cell adhesion to fibronectin and the basic helix-loop-helix
      transcription factor Twist1. Depletion of Twist1 mRNA by small interfering RNA
      resulted in decreased expression of both Twist1 and N-cadherin and the inhibition
      of cell migration. Whereas Twist1 gene expression was independent of beta(1)
      integrin-mediated adhesion, Twist1 protein failed to accumulate in the nuclei of
      cells cultured in anchorage-independent conditions. The increased nuclear
      accumulation of Twist1 following cell attachment was suppressed by treatment with
      an inhibitor of Rho kinase or a beta(1) integrin neutralizing antibody. The
      effect of Twist1 on induction of N-cadherin mRNA required an E-box cis-element
      located within the first intron (+2,627) of the N-cadherin gene. These data raise
      the possibility that integrin-mediated adhesion to interstitial matrix proteins
      during metastasis differentially regulates the nuclear/cytoplasmic translocation
      and DNA binding of Twist1, activating N-cadherin transcription.

PMID- 16585156
TI  - Akt-mediated phosphorylation and activation of estrogen receptor alpha is
      required for endometrial neoplastic transformation in Pten+/- mice.
AB  - PTEN is a tumor suppressor gene frequently mutated in human cancers. In vitro and
      in vivo studies have shown that PTEN can exert its tumor suppressive function
      through a variety of mechanisms, including regulation of cell death and cell
      proliferation. However, it is still unclear which of the many downstream pathways
      are critical in each different tissue, in vivo. Loss of PTEN is the earliest
      detectable genetic lesion in the estrogen-related type I (endometrioid)
      endometrial cancer. Pten(+/-) mice develop endometrial neoplastic lesions with
      full penetrance, thus providing a model system to dissect the genetic and
      biochemical events leading to the transition from normal to hyperplastic and
      neoplastic endometrial epithelium. Here, we show that loss of Pten in the mouse
      endometrium activates Akt and results in increased phosphorylation of estrogen
      receptor alpha (ERalpha) on Ser(167). ERalpha phosphorylation results, in turn,
      in the activation of this nuclear receptor both in vivo and in vitro, even in the
      absence of ligand, and in its increased ability to activate the transcription of
      several of its target genes. Strikingly, reduction of endometrial ERalpha levels
      and activity dramatically reduces the neoplastic effect of Pten loss in the
      endometrium, in contrast to complete estrogen depletion. Thus, we provide for the
      first time in vivo evidence supporting the hypothesis that loss of Pten and
      subsequent Akt activation result in the activation of ERalpha-dependent pathways
      that play a pivotal role in the neoplastic process.

PMID- 16585157
TI  - Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients
      with long-term follow-up.
AB  - B7-H1 participates in T-cell costimulation functioning as a negative regulator of
      immunity. Recent observations suggest that B7-H1 is expressed by renal cell
      carcinoma (RCC) tumor cells and is associated with poor prognosis. However,
      outcome analyses have been restricted to patients with fresh-frozen tissue and
      limited follow-up. We report the clinical effect of B7-H1 in RCC patients with a
      median of 10 years of follow-up. Between 1990 and 1994, 306 patients underwent
      nephrectomy for clear cell RCC and had paraffin tissue available for review. We
      did immunohistochemistry with anti-B7-H1 and conducted outcome analyses. Among
      the 306 patients, 73 (23.9%) harbored tumors with B7-H1 expression. Patients with
      tumor B7-H1 were at a significantly increased risk of both death from RCC [risk
      ratio (RR), 3.92; P < 0.001] and overall mortality (RR, 2.37; P < 0.001). The 5
      year cancer-specific survival rates were 41.9% and 82.9% for patients with and
      without tumor B7-H1, respectively. In a multivariate model, tumor B7-H1 remained
      associated with cancer-specific death even after adjusting for tumor-node
      metastasis stage, grade, and performance status (RR, 2.00; P = 0.003). In the
      subset of 268 patients with localized RCC, tumor B7-H1 was significantly
      associated with metastatic cancer progression (RR, 3.46; P < 0.001) and death
      from RCC (RR, 4.13; P < 0.001) even after adjusting for stage, grade, and
      performance status (RR, 1.78, P = 0.036). RCC patients with tumor B7-H1 are at
      significant risk of rapid cancer progression and accelerated rates of mortality.
      B7-H1 may function as a key determinant in RCC, abrogating immune responses
      directed against this immunogenic tumor.

PMID- 16585158
TI  - Highly efficacious nontoxic preclinical treatment for advanced metastatic breast
      cancer using combination oral UFT-cyclophosphamide metronomic chemotherapy.
AB  - Metronomic antiangiogenic chemotherapy, the prolonged administration of
      relatively low drug doses, at close regular intervals with no significant breaks,
      has been mainly studied at the preclinical level using single chemotherapeutic
      drugs, frequently in combination with a targeted antiangiogenic drug, and almost
      always evaluated on primary localized tumors. We tested a "doublet" combination
      metronomic chemotherapy treatment using two oral drugs, UFT, a 5-fluorouracil (5
      FU) prodrug administered by gavage, and cyclophosphamide, for efficacy and
      toxicity in a new mouse model of advanced, terminal, metastatic human breast
      cancer. The optimal biological dose of each drug was first determined by effects
      on levels of circulating endothelial progenitor cells as a surrogate marker for
      angiogenesis, which was assessed to be 15 mg/kg for UFT and 20 mg/kg for
      cyclophosphamide. A combination treatment was then evaluated in mice with
      advanced metastatic disease using a serially selected metastatic variant of the
      MDA-MB-231 breast cancer-cell line, 231/LM2-4. UFT or cyclophosphamide treatment
      showed only very modest survival advantages whereas a combination of the two
      resulted in a remarkable prolongation of survival, with no evidence of overt
      toxicity despite 140 days of continuous therapy, such that a significant
      proportion of mice survived for over a year. In contrast, this striking
      therapeutic effect of the combination treatment was not observed when tested on
      primary orthotopic tumors. We conclude that combination oral low-dose daily
      metronomic chemotherapy, using cyclophosphamide and UFT, is superior to
      monotherapy and seems to be a safe and highly effective experimental
      antimetastatic therapy, in this case, for advanced metastatic breast cancer.

PMID- 16585159
TI  - Mitosis-independent survivin gene expression in vivo and regulation by p53.
AB  - Survivin is an essential mitotic gene, and this has been speculated to reflect
      its primary function in development and cancer. Here, we generated a knock-in
      transgenic mouse (SVVp-GFP) in which a green fluorescent protein (GFP) reporter
      gene was placed under the control of the survivin promoter that regulates
      transcription at mitosis. The expression of endogenous survivin was widespread in
      mouse tissues during development and shortly after birth. In contrast, GFP
      reactivity was undetectable in transgenic mouse embryos, and was largely limited
      postnatally to mitotic cells in the testes. Double transgenic mice generated in
      the tumor-prone Min/+ background exhibited intestinal adenomas that strongly
      expressed endogenous survivin, but only isolated GFP-positive cells. Conversely,
      dysplastic adenomas (16%) stained intensely for GFP, and revealed focal
      reactivity for mutant, but not wild-type, p53. The expression of GFP was
      increased by approximately 10-fold in p53(-/-) as opposed to p53(+/+) HCT116
      colorectal cancer cells, and reintroduction of p53 in p53(-/-) cells abolished
      GFP expression. Therefore, the mitotic transcription of the survivin gene is
      highly restricted in vivo, and unexpectedly negatively regulated by p53. Contrary
      to a commonly held view, the dominant function(s) of survivin in development and
      tumor ontogeny are largely cell cycle-independent.

PMID- 16585160
TI  - TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer.
AB  - Although common in hematologic and mesenchymal malignancies, recurrent gene
      fusions have not been well characterized in epithelial carcinomas. Recently,
      using a novel bioinformatic approach, we identified recurrent gene fusions
      between TMPRSS2 and the ETS family members ERG or ETV1 in the majority of
      prostate cancers. Here, we interrogated the expression of all ETS family members
      in prostate cancer profiling studies and identified marked overexpression of ETV4
      in 2 of 98 cases. In one such case, we confirmed the overexpression of ETV4 using
      quantitative PCR, and by rapid amplification of cDNA ends, quantitative PCR, and
      fluorescence in situ hybridization, we show that the TMPRSS2 (21q22) and ETV4
      (17q21) loci are fused in this case. This result defines a third molecular
      subtype of prostate cancer and supports the hypothesis that dysregulation of ETS
      family members through fusions with TMRPSS2 may be an initiating event in
      prostate cancer development.

PMID- 16585161
TI  - Two transforming C-RAF germ-line mutations identified in patients with therapy
      related acute myeloid leukemia.
AB  - Mutations leading to activation of the RAF-mitogen-activated protein
      kinase/extracellular signal-regulated (ERK) kinase (MEK)-ERK pathway are key
      events in the pathogenesis of human malignancies. In a screen of 82 acute myeloid
      leukemia (AML) samples, 45 (55%) showed activated ERK and thus were further
      analyzed for mutations in B-RAF and C-RAF. Two C-RAF germ-line mutations, S427G
      and I448V, were identified in patients with therapy-related AML in the absence of
      alterations in RAS and FLT3. Both exchanges were located within the kinase domain
      of C-RAF. In vitro and in vivo kinase assays revealed significantly increased
      activity for (S427G)C-RAF but not for (I448V)C-RAF. The involvement of the S427G
      C-RAF mutation in constitutive activation of ERK was further confirmed through
      demonstration of activating phosphorylations on C-RAF, MEK, and ERK in neoplastic
      cells, but not in nonneoplastic cells. Transformation and survival assays showed
      oncogenic and antiapoptotic properties for both mutations. Screening healthy
      individuals revealed a <1/400 frequency of these mutations and, in the case of
      I448V, inheritance was observed over three generations with another mutation
      carrier suffering from cancer. Taken together, these data are the first to relate
      C-RAF mutations to human malignancies. As both mutations are of germ-line origin,
      they might constitute a novel tumor-predisposing factor.

PMID- 16585162
TI  - N-methyl-D-aspartate receptor type 2B is epigenetically inactivated and exhibits
      tumor-suppressive activity in human esophageal cancer.
AB  - Promoter hypermethylation accompanied by gene silencing is a common feature of
      human cancers. We identified previously several new tumor suppressor genes based
      on pharmacologic unmasking of the promoter region and detection of reexpression
      on microarray analysis. In this study, we modified the selection of candidates
      from our previous microarray data by excluding genes that showed basal expression
      in cancer cell lines. With the new method, we found novel methylated genes with
      90% accuracy. Among these 33 novel methylated genes that we identified in
      esophageal squamous cell carcinoma (ESCC) cell lines, N-methyl-D-aspartate
      receptor type 2B (NMDAR2B) was of particular interest. NMDAR2B was methylated in
      95% of primary human ESCC tissue specimens and 12 ESCC cell lines by sequence
      analysis. NMDAR2B expression was silenced in all 12 ESCC cell lines and was
      reactivated by the demethylating agent 5-aza-2'-deoxycytidine. Moreover,
      reintroduction of the gene was accompanied by marked Ca(2+)-independent apoptosis
      in ESCC cell lines, suggesting that NMDAR2B can suppress tumor growth. Thus,
      NMDAR2B promoter methylation is common in ESCC, abrogating gene transcription and
      leading to cellular resistance to apoptosis.

PMID- 16585163
TI  - 3p21.3 tumor suppressor gene H37/Luca15/RBM5 inhibits growth of human lung cancer
      cells through cell cycle arrest and apoptosis.
AB  - Deletion at chromosome 3p21.3 is the earliest and the most frequently observed
      genetic alteration in lung cancer, suggesting that the region contains tumor
      suppressor gene(s) (TSG). Identification of those genes may lead to the
      development both of biomarkers to identify high-risk individuals and novel
      therapeutics. Previously, we cloned the H37/Luca15/RBM5 gene from 3p21.3 and
      showed its TSG characteristics. To investigate the physiologic function of H37 in
      the lung and its mechanism of tumor suppression, we have stably transfected H37
      into A549 non-small cell lung cancer cells. A549/H37 cells show significant
      growth inhibition compared with the vector controls by in vitro and in vivo cell
      proliferation assays. Using this lung cancer cell model, we have found that the
      molecular mechanism of H37 tumor suppression involves both cell cycle (G(1))
      arrest and apoptosis. To further define H37's function in cell cycle/apoptotic
      pathways, we investigated differential expression profiles of various cell cycle
      and apoptosis regulatory proteins using Western blot analysis. Both cyclin A and
      phophorylated RB levels were decreased in H37-transfected cells, whereas
      expression of Bax protein was increased. Mitochondrial regulation of apoptosis
      further downstream of Bax was investigated, showing change in the mitochondrial
      membrane potential, cytochrome c release into the cytosol, and enhanced caspase-9
      and caspase-3 activities. We also report that H37 may mediate apoptosis in a p53
      independent manner, and Bax knockdown by small interfering RNA suggests Bax plays
      a functional role downstream of H37. Lastly, we proposed a tumor suppression
      model of H37 as a post-transcriptional regulator for cell cycle/apoptotic-related
      proteins.

PMID- 16585164
TI  - Abnormal gene expression profiles in unaffected parents of patients with
      hereditary-type retinoblastoma.
AB  - The hereditary form of retinoblastoma (Rb) is associated with a germ line
      mutation in one RB allele and is characterized by the occurrence of multiple,
      bilateral Rb tumors and a predisposition to the development of second cancers. In
      an earlier study, we observed an unexpected hypersensitivity to ionizing
      radiation in skin fibroblasts derived from unaffected parents of children with
      hereditary Rb. In at least four of these five families, there was no family
      history of Rb, indicating a new germ line mutation. We hypothesize that the
      increased parental cell sensitivity to radiation may reflect the presence of an
      as yet unrecognized genetic abnormality occurring in one or both parents of
      children with Rb. In the present study, we use DNA microarray technology to
      determine whether differences in gene expression profiles occurred in the
      unaffected parents of patients with hereditary Rb relative to normal individuals.
      Microarray analyses were validated by quantitative reverse transcription-PCR
      measurements. A distinct difference was observed in the patterns of gene
      expression between unaffected Rb parents and normal controls. By use of the
      prediction analysis for microarrays and principal component analysis
      methodologies, significant differences between the two groups were identified
      when as few as nine genes were analyzed. Further study of this phenomenon may
      offer a new insight into the genetic mechanisms of Rb and perhaps more broadly in
      cancer biology.

PMID- 16585165
TI  - SOX4 expression in bladder carcinoma: clinical aspects and in vitro functional
      characterization.
AB  - The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors
      compared with normal tissue based on whole-genome expression profiling of 166
      clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4
      specific antibody, we found that the cancer cells expressed the SOX4 protein and,
      thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using
      a tissue microarray with clinical annotation. We found a correlation (P < 0.05)
      between strong SOX4 expression and increased patient survival. When overexpressed
      in the bladder cell line HU609, SOX4 strongly impaired cell viability and
      promoted apoptosis. To characterize downstream target genes and SOX4-induced
      pathways, we used a time-course global expression study of the overexpressed
      SOX4. Analysis of the microarray data showed 130 novel SOX4-related genes, some
      involved in signal transduction (MAP2K5), angiogenesis (NRP2), and cell cycle
      arrest (PIK3R3) and others with unknown functions (CGI-62). Among the genes
      regulated by SOX4, 25 contained at least one SOX4-binding motif in the promoter
      sequence, suggesting a direct binding of SOX4. The gene set identified in vitro
      was analyzed in the clinical bladder material and a small subset of the genes
      showed a high correlation to SOX4 expression. The present data suggest a role of
      SOX4 in the bladder cancer disease.

PMID- 16585166
TI  - A single nucleotide polymorphism chip-based method for combined genetic and
      epigenetic profiling: validation in decitabine therapy and tumor/normal
      comparisons.
AB  - Progress on several unresolved issues in cancer epigenetics will benefit from
      rapid and standardized methods for profiling DNA methylation genome-wide. In the
      area of epigenetic therapy, the demethylating drug decitabine (5-aza-2'
      deoxycytidine) is increasingly used to treat acute myelogenous leukemia and
      myelodysplastic syndrome, but the mechanisms of its anticancer activity have
      remained unclear. Given the clinical efficacy of decitabine and the uncertainties
      about its mode of action, it will be useful to optimize methods for following DNA
      methylation as a biochemical response in individual patients. Here, we describe a
      single nucleotide polymorphism (SNP) chip-based method (MSNP) for profiling DNA
      methylation. Using this procedure, the extent of demethylation in bone marrow
      aspirates from patients with leukemia receiving decitabine can be assessed genome
      wide using commercially available (Affymetrix) SNP chips. We validated the
      accuracy of MSNP by comparing the results with combined bisulfite restriction
      analysis and by sequencing cloned PCR products from bisulfite-converted DNA. We
      further validated MSNP in a Wilms' tumor/normal kidney comparison, comparing the
      results with methylation-sensitive Southern blotting. MSNP simultaneously detects
      aberrations in DNA copy number and loss of heterozygosity, making it a generally
      useful approach for combined genetic and epigenetic profiling in tissue samples
      from cancer patients.

PMID- 16585167
TI  - Frequent met oncogene amplification in a Brca1/Trp53 mouse model of mammary
      tumorigenesis.
AB  - In a screen for gene copy number alterations in mouse mammary tumors initiated by
      loss of the Brca1 and Trp53 genes, we observed that the majority (11 of 15; 73%)
      had high-level amplification of wild-type Met, encoding a growth factor receptor
      implicated in tumor progression. Met amplification was localized to unstable
      double minute chromosomes and was uniquely found in mouse breast tumors driven by
      loss of Brca1 and Trp53. Whereas analogous MET amplification was not found in
      human breast cancers, the identification of a dominant somatic genetic lesion in
      the Brca1/Trp53 mouse model suggests that recurrent secondary hits may also exist
      in BRCA1-initiated human breast cancer.

PMID- 16585168
TI  - Targeted ablation of Par-4 reveals a cell type-specific susceptibility to
      apoptosis-inducing agents.
AB  - The prostate apoptosis response-4 (Par-4) protein has been shown to function as
      an effector of cell death in response to various apoptotic stimuli, and down
      regulation of this protein has been suggested to be a key event during
      tumorigenesis. Several studies suggest an essential function for the COOH
      terminal leucine repeats/death domain of Par-4 in mediating apoptosis. We
      investigated the biological role of this domain in vivo by generating knock-out
      mice expressing a Par-4 mutant protein lacking the COOH terminus domain. We found
      that the Par-4 mutant mice are viable and fertile with no overt phenotype, thus
      excluding an essential role for the COOH terminus domain of Par-4 in
      embryogenesis and developmental apoptosis. To determine the requirement of Par-4
      for apoptosis, we treated primary fibroblasts with various stimuli that trigger
      mitochondria and membrane receptor cell death pathways. Fibroblasts isolated from
      Par-4 mutant mice are as sensitive as the wild-type cells to these apoptosis
      inducing agents. Similar effects were observed following RNA interference (RNAi)
      mediated knockdown of Par-4 in these cells. In contrast, RNAi-mediated depletion
      of Par-4 in HeLa cells resulted in a significant inhibition of apoptosis induced
      by various proapoptotic agents. Taken together, our findings provide strong
      genetic evidence that the proapoptotic function of Par-4 is dependent on the
      cellular context and raise the possibility that alterations of Par-4 function may
      occur during carcinogenesis.

PMID- 16585169
TI  - Mouse double minute 2 associates with chromatin in the presence of p53 and is
      released to facilitate activation of transcription.
AB  - The tumor suppressor p53 is a potent transcription factor of which the ability to
      mediate transcription is inhibited through an interaction with the oncoprotein
      mouse double minute 2 (Mdm2). The present study has tested the hypothesis that
      Mdm2 inhibits the p53 response in normally growing cells by binding to chromatin
      associated p53. Using chromatin immunoprecipitation, we show that Mdm2 localizes
      with p53 at its responsive elements on the waf1 and mdm2 genes in human cell
      lines expressing p53, but not in cell lines lacking p53 expression, indicating
      that Mdm2 is recruited to regions of DNA in a p53-dependent manner.
      Interestingly, our results show a decrease of Mdm2 protein associated with p53
      responsive elements on the waf1 and mdm2 genes when p53-induced transcription is
      activated either by DNA damage or through controlled overexpression of p53. Rapid
      activation of p53 transcriptional activity before increasing p53 protein levels
      was observed with addition of either small-molecule inhibitors to disrupt the p53
      Mdm2 interaction or small interfering RNA to mdm2. These findings indicate Mdm2
      transiently localizes with p53 at responsive elements and suggest that latent p53
      results from the recruitment of Mdm2 to chromatin.

PMID- 16585170
TI  - Combined array-comparative genomic hybridization and single-nucleotide
      polymorphism-loss of heterozygosity analysis reveals complex changes and multiple
      forms of chromosomal instability in colorectal cancers.
AB  - Cancers with chromosomal instability (CIN) are held to be aneuploid/polyploid
      with multiple large-scale gains/deletions, but the processes underlying CIN are
      unclear and different types of CIN might exist. We investigated colorectal cancer
      cell lines using array-comparative genomic hybridization (CGH) for copy number
      changes and single-copy number polymorphism (SNP) microarrays for allelic loss
      (LOH). Many array-based CGH changes were not found by LOH because they did not
      cause true reduction-to-homozygosity. Conversely, many regions of SNP-LOH
      occurred in the absence of copy number change, comprising an average per cell
      line of 2 chromosomes with complete LOH; 1-2 terminal regions of LOH (mitotic
      recombination); and 1 interstitial region of LOH. SNP-LOH detected many novel
      changes, representing possible locations of uncharacterized tumor suppressor
      loci. Microsatellite unstable (MSI+) lines infrequently showed gains/deletions or
      whole-chromosome LOH, but their near-diploid karyotypes concealed mitotic
      recombination frequencies similar to those of MSI- lines. We analyzed p53 and
      chromosome 18q (SMAD4) in detail, including mutation screening. Almost all MSI-
      lines showed LOH and/or deletion of p53 and 18q; some near-triploid lines had
      acquired three independent changes at these loci. We found consistent results in
      primary colorectal cancers. Overall, the distributions of mitotic recombination
      and whole-chromosome LOH in the MSI- cell lines differed significantly from
      random, with some lines having much higher than expected levels of these changes.
      Moreover, lines with more LOH changes had significantly fewer copy number
      changes. These data suggest that CIN is not synonymous with copy number change
      and some cancers have a specific tendency to whole-chromosome deletion and regain
      or to mitotic recombination.

PMID- 16585171
TI  - Carcinogenic Cr(VI) and the nutritional supplement Cr(III) induce DNA deletions
      in yeast and mice.
AB  - Industrial Cr(VI) emissions contaminate drinking water sources across the U.S.,
      and many people take Cr(III) nutritional supplements. Cr(VI) is a human pulmonary
      carcinogen, but whether it is carcinogenic in the drinking water is not known.
      Due to widespread human exposure, it is imperative to determine the carcinogenic
      potential of Cr(VI) and Cr(III). DNA deletions and other genome rearrangements
      are involved in carcinogenesis. We determined the effects of Cr(VI) as potassium
      dichromate and Cr(III) as chromium(III) chloride on the frequencies of DNA
      deletions measured with the deletion assay in Saccharomyces cerevisiae and the in
      vivo p(un) reversion assay in C57BL/6J p(un)/p(un) mice. Exposing yeast and mice
      via drinking water to Cr(VI) and Cr(III) significantly increased the frequency of
      DNA deletions. We quantified intracellular chromium concentrations in yeast and
      tissue chromium concentrations in mice after exposure. Surprisingly, this
      revealed that Cr(III) is a more potent inducer of DNA deletions than Cr(VI) once
      Cr(III) is absorbed. This study concludes that both the environmental contaminant
      Cr(VI) and the nutritional supplement Cr(III) increase DNA deletions in vitro and
      in vivo, when ingested via drinking water.

PMID- 16585172
TI  - The p53 pathway promotes efficient mitochondrial DNA base excision repair in
      colorectal cancer cells.
AB  - The tumor suppressor p53 plays a central role in the DNA damage response. p53
      enhances base excision repair (BER), in part, through direct interaction with the
      repair complex. Mitochondrial DNA (mtDNA) is repaired by a mtBER pathway. Many
      colorectal cancers harbor mtDNA mutations that are associated with poor
      prognosis. In addition to modulating the apoptotic response, mitochondria
      localized p53 also stimulates mtBER. However, the mechanisms by which p53
      enhances colorectal cancer mtBER after stress remain unclear. To explore this, we
      used colorectal cancer cells isogenic for p53 (HCT116p53+/+ and HCT116p53-/-).
      p53+/+ cells more efficiently repaired H(2)O(2) damaged DNA in vivo as measured
      by semiquantitative mtDNA displacement loop PCR. Mitochondrial extracts from
      p53+/+ cells more efficiently stimulated (32)P-dCTP incorporation into a uracil
      oligonucleotide. Recombinant p53 complemented p53-/- mitochondrial extract repair
      of uracil or 8-oxo-G-containing oligonucleotides. As a measure of DNA glycosylase
      activity, p53+/+ mitochondrial extracts more efficiently incised uracil or 8-oxo
      G oligonucleotides, although recombinant p53 could not stimulate oligonucleotide
      incision. p53 did not influence mitochondrial apurinic/apyrimidinic endonuclease
      activity measured by incision of a tetrahydrofuran-oligonucleotide. p53+/+
      mitochondrial extracts had higher DNA polymerase-gamma activity measured by (32)P
      dCTP incorporation into a single-nucleotide gap oligonucleotide, and recombinant
      p53 complemented p53-/- mitochondrial extract DNA polymerase-gamma activity.
      mtDNA ligase activity was not affected by p53 status. p53 protein was detected in
      an inner mitochondrial membrane subfraction containing components of the mtBER
      complex. Our data suggest that an intact p53 pathway stimulates specific mtBER
      steps and provides mechanistic insight into the development of mtDNA mutations in
      colorectal cancer.

PMID- 16585173
TI  - Distinct tumor stage-specific inhibitory effects of 2-methoxyestradiol in a
      breast cancer mouse model associated with Id-1 expression.
AB  - 2-Methoxyestradiol (2ME(2)), a metabolite of 17-beta-estradiol, inhibits
      angiogenesis and has additional antitumor activities. We have analyzed the tumor
      stage-specific effects of 2ME(2) in the C3(1)/Tag transgenic mouse model for
      breast cancer, which spontaneously develops estrogen receptor-negative mammary
      tumors following a predictable progression of lesion formation. When given either
      as a therapeutic agent in established tumors (late intervention study) or in mice
      with pre-invasive mammary lesions (early intervention study), tumor growth was
      reduced by 60% compared with untreated controls and was associated with an
      induction of apoptosis. In a prevention study, a significant reduction in mammary
      intraepithelial neoplasia (MIN) lesions was observed in animals beginning
      treatment at 6 weeks of age, before the appearance of histopathologic
      abnormalities. However, although 2ME(2) reduced the number of MIN lesions in the
      prevention study, a paradoxical increase in tumor multiplicity and growth rate
      was observed. This was associated with unusual cystic tumor formation, in which
      significant central necrosis was observed, surrounded by an outer region of
      proliferative tumor cell growth. The characteristics of the cystic tumor
      formation in mice treated with 2ME(2) at early ages are consistent with an
      impaired angiogenic response as observed in mice deficient for inhibitor of
      differentiation (Id-1). We further show that Id-1 expression is negatively
      regulated by 2ME(2), which may be an additional mechanism for the antiangiogenic
      effect of 2ME(2). Although 2ME(2) significantly reduced tumor growth at late
      stages, these results also suggest that altered tumor morphology and accelerated
      tumor growth may occur if 2ME(2) is administered in a prevention setting for
      prolonged periods.

PMID- 16585174
TI  - Gastrin enhances the angiogenic potential of endothelial cells via modulation of
      heparin-binding epidermal-like growth factor.
AB  - This study examined whether gastrin modulates endothelial cell activity via
      heparin-binding epidermal growth factor-like growth factor (HB-EGF) expression.
      Human umbilical vascular endothelial cells (HUVEC) were assessed for tubule
      formation in the presence of amidated gastrin-17 (G17) and glycine-extended
      gastrin-17 (GlyG17) peptides. HB-EGF gene and protein expressions were measured
      by quantitative reverse transcription-PCR, immunocytochemistry, and Western
      blotting, and HB-EGF shedding by ELISA. Matrix metalloproteinases MMP-2, MMP-3,
      and MMP-9 were assessed by Western blotting. Chick chorioallantoic membrane
      studies measured the in vivo angiogenic potential of gastrin and microvessel
      density (MVD) was assessed in large intestinal premalignant lesions of
      hypergastrinaemic APC(Min) mice. MVD was also examined in human colorectal tumor
      and resection margin normals and correlated with serum-amidated gastrin levels
      (via RIA) and HB-EGF protein expression (via immunohistochemistry). HUVEC cells
      showed increased tubule and node formation in response to G17 (186%, P < 0.0005)
      and GlyG17 (194%, P < 0.0005). This was blockaded by the cholecystokinin-2
      receptor (CCK-2R) antagonists JB95008 and JMV1155 and by antiserum to gastrin and
      HB-EGF. Gastrin peptides increased HB-EGF gene expression/protein secretion in
      HUVEC and microvessel-derived endothelial cells and the levels of MMP-2, MMP-3,
      and MMP-9. G17 promoted angiogenesis in a chorioallantoic membrane assay, and MVD
      was significantly elevated in premalignant large intestinal tissue from
      hypergastrinaemic APC(Min) mice. In terms of the clinical situation, MVD in the
      normal mucosa surrounding colorectal adenocarcinomas correlated with patient
      serum gastrin levels and HB-EGF expression. Gastrin peptides, acting through the
      CCK-2R, enhance endothelial cell activity in models of angiogenesis. This may be
      mediated through enhanced expression and shedding of HB-EGF, possibly resulting
      from increased activity of matrix metalloproteinases. This proangiogenic effect
      translates to the in vivo and human situations and may add to the tumorigenic
      properties attributable to gastrin peptides in malignancy.

PMID- 16585175
TI  - Adenoviral gene transfer of stromal cell-derived factor-1 to murine tumors
      induces the accumulation of dendritic cells and suppresses tumor growth.
AB  - The human CXC chemokine, stromal cell-derived factor 1 (SDF-1alpha), is known to
      function in vitro as a chemotactic factor for lymphocytes, monocytes, and
      dendritic cells. In the context that dendritic cells are powerful antigen
      presenting cells, we hypothesized that adenoviral gene transfer of SDF-1alpha to
      tumors might inhibit growth of preexisting tumors through attracting dendritic
      cells to the tumor. AdSDF-1alpha mediated the expression of SDF-1alpha mRNA and
      protein in A549 cells in vitro, and the supernatant of the AdSDF-1alpha-infected
      A549 cells showed chemotactic activity for dendritic cells. When syngeneic murine
      CT26 colon carcinoma tumors (BALB/c) and B16 melanoma and Lewis lung cell
      carcinoma (C57Bl/6) were injected with AdSDF-1alpha (5 x 10(8) plaque-forming
      units), there was an accumulation of dendritic cells and CD8(+) cells within the
      tumor and significant inhibition of tumor growth compared with tumors injected
      with PBS or AdNull (control vector). The injection of AdSDF-1alpha into tumors
      induced the inflammatory enlargement and the accumulation of dendritic cells in
      the draining lymph node. Intratumoral AdSDF-1alpha administration elicited tumor
      specific CTLs and adoptive transfer of splenocytes from AdSDF-1alpha-treated mice
      resulted in the elongation of survival after tumor challenge. Interestingly, in
      wild-type and CD4(-/-) mice but not in CD8(-/-) mice, AdSDF-1alpha inhibited the
      growth of the tumor. These observations suggest that adenoviral gene transfer of
      SDF-1alpha may be a useful strategy to accumulate dendritic cells in tumors and
      evoke antitumor immune responses to inhibit tumor growth.

PMID- 16585176
TI  - Growth and motility inhibition of breast cancer cells by epidermal growth factor
      receptor degradation is correlated with inactivation of Cdc42.
AB  - Overexpression of epidermal growth factor receptor (EGFR) contributes to
      increased cell proliferation and migration in breast cancer. However, mechanisms
      of EGFR overexpression remain elusive and often cannot be attributed to gene
      amplification. In NIH3T3 fibroblasts, active Cdc42 inhibits c-Cbl-regulated EGFR
      degradation to induce cellular transformation. Here, we use two EGFR
      overexpressing breast cancer cell lines, MDA-MB-231 and BT20, as models to test
      the hypothesis that up-regulated Cdc42 activity impairs c-Cbl-mediated EGFR
      degradation and contributes to EGFR overexpression. We show that silencing Cdc42
      significantly reduces protein levels of EGFR, leading to a marked reduction in
      cell proliferation and migration, and c-Cbl knockdown increases the levels of
      EGFR. Expression of c-Cbl-N480, a c-Cbl mutant that is not regulated by Cdc42 and
      blocks Cdc42-induced transformation but still binds and ubiquitinates EGFR,
      enhances the rate of EGFR degradation and subsequently inhibits cell
      proliferation. Moreover, down-regulated EGFR signaling induced by c-Cbl-N480
      decreased activity of Cdc42 and Rac1, resulting in inhibition of cell migration.
      These findings indicate that Cdc42 and c-Cbl are critical components involved in
      the regulation of EGFR protein levels and that restoration of proper EGFR
      degradation by disrupting Cdc42 regulation of c-Cbl can reduce cell proliferation
      and migration in MDA-MB-231 and BT20 cells.

PMID- 16585177
TI  - hTERT-immortalized prostate epithelial and stromal-derived cells: an authentic in
      vitro model for differentiation and carcinogenesis.
AB  - Prostate cancer is the most commonly diagnosed type of cancer in men, and there
      is no available cure for patients with advanced disease. In vitro model systems
      are urgently required to permit the study of human prostate cell differentiation
      and malignant transformation. Unfortunately, human prostate cells are
      particularly difficult to convert into continuously growing cultures. We report
      here the successful immortalization without viral oncogenes of prostate
      epithelial cells and, for the first time, prostate stromal cells. These cells
      exhibit a significant pattern of authentic prostate-specific features. In
      particular, the epithelial cell culture is able to differentiate into glandular
      buds that closely resemble the structures formed by primary prostate epithelial
      cells. The stromal cells have typical characteristics of prostate smooth muscle
      cells. These immortalized cultures may serve as a unique experimental platform to
      permit several research directions, including the study of cell-cell interactions
      in an authentic prostate microenvironment, prostate cell differentiation, and
      most significantly, the complex multistep process leading to prostate cell
      transformation.

PMID- 16585178
TI  - Silenced tumor suppressor genes reactivated by DNA demethylation do not return to
      a fully euchromatic chromatin state.
AB  - Histone H3 lysine 9 (H3K9) and lysine 27 (H3K27) trimethylation are properties of
      stably silenced heterochromatin whereas H3K9 dimethylation (H3K9me2) is important
      for euchromatic gene repression. In colorectal cancer cells, all of these marks,
      as well as the key enzymes which establish them, surround the hMLH1 promoter when
      it is DNA hypermethylated and aberrantly silenced, but are absent when the gene
      is unmethylated and fully expressed in a euchromatic state. When the aberrantly
      silenced gene is DNA demethylated and reexpressed following 5-aza-2'
      deoxycytidine treatment, H3K9me1 and H3K9me2 are the only silencing marks that
      are lost. A series of other silenced and DNA hypermethylated gene promoters
      behave identically even when the genes are chronically DNA demethylated and
      reexpressed after genetic knockout of DNA methyltransferases. Our data indicate
      that when transcription of DNA hypermethylated genes is activated in cancer
      cells, their promoters remain in an environment with certain heterochromatic
      characteristics. This finding has important implications for the translational
      goal of reactivating aberrantly silenced cancer genes as a therapeutic maneuver.

PMID- 16585179
TI  - Constitutive activation of extracellular signal-regulated kinase predisposes
      diffuse large B-cell lymphoma cell lines to CD40-mediated cell death.
AB  - CD40 promotes survival, proliferation, and differentiation of normal B cells but
      can cause activation-induced cell death in malignant B lymphocytes. CD40 ligand
      and anti-CD40 antibodies have been used successfully to induce apoptosis in
      lymphoma lines both in vitro and in xenograft tumor models. Although this makes
      CD40 an attractive target for antitumor therapies, the response of malignant B
      cells to CD40 signaling is variable, and CD40 stimulation can enhance
      proliferation and can increase chemoresistance in some cell lines. It would
      therefore be useful to identify markers that predict whether a specific cell line
      or tumor will undergo apoptosis when stimulated with CD40 and to identify targets
      downstream of CD40 that affect only the apoptotic arm of CD40 signaling. We have
      analyzed gene expression patterns in CD40-sensitive and CD40-resistant diffuse
      large B-cell lymphoma (DLBCL) cell lines to identify signaling pathways that are
      involved in CD40-mediated apoptosis. CD40-resistant lines expressed pre-B-cell
      markers, including RAG and VPREB, whereas CD40-sensitive cells resembled mature B
      cells and expressed higher levels of transcripts encoding several members of the
      CD40 signaling pathway, including LCK and VAV. In addition, CD40-sensitive DLBCL
      cell lines also displayed constitutive activation of extracellular signal
      regulated kinase (ERK) and failed to undergo apoptosis when ERK phosphorylation
      was inhibited. In contrast, CD40-resistant lines showed no constitutive
      activation of ERK and no increase in ERK activity in response to CD40
      stimulation. Our results suggest that constitutive activation of ERK may be
      required for death signaling by CD40.

PMID- 16585180
TI  - Chemical enhancers of cytokine signaling that suppress microfilament turnover and
      tumor cell growth.
AB  - The transforming growth factor-beta (TGF-beta) family of cytokines regulates cell
      proliferation, morphogenesis, and specialized cell functions in metazoans.
      Herein, we screened a compound library for modifiers of TGF-beta signaling in
      NMuMG epithelial cells using a cell-based assay to measure Smad2/3 nuclear
      translocation. We identified five enhancers of TGF-beta signaling that share a
      core structure of diethyl 2-(anilinomethylene)malonate (DAM), and D(50) values of
      1 to 4 micromol/L. Taking advantage of the Mgat5 mutant phenotype of accelerated
      receptor loss to endocytosis, we determined that DAM-1976 restored the
      sensitivity of Mgat5(-/-) carcinoma cells to both TGF-beta and epidermal growth
      factor (EGF). In Mgat5 mutant and wild-type carcinoma cells, DAM-1976 enhanced
      and prolonged TGF-beta- and EGF-dependent Smad2/3 and Erk activation,
      respectively. DAM-1976 reduced ligand-dependent EGF receptor endocytosis, actin
      microfilament turnover, and cell spreading, suggesting that the compound
      attenuates vesicular trafficking. Hyperactivation of intracellular signaling has
      the potential to suppress tumor cell growth and, in this regard, DAM-1976
      represents a new pharmacophore that increases basal activation of Smad2/3 and
      Erk, inhibits microfilament remodeling, and suppresses carcinoma cell growth.

PMID- 16585181
TI  - Regulation of E-cadherin expression by VHL and hypoxia-inducible factor.
AB  - Mutations in von Hippel-Lindau tumor suppressor gene (VHL) underlie the VHL
      hereditary cancer syndrome and also occur in most sporadic clear cell renal cell
      cancers (CCRCC). Currently, the mechanism(s) by which VHL loss of function
      promotes tumor development in the kidney are not fully elucidated. Here, we show
      that VHL inactivation in precancerous lesions in kidneys from patients with VHL
      disease correlates with marked down-regulation of the intercellular adhesion
      molecule E-cadherin. Moreover, in VHL-defective cell lines (RCC4 and RCC10)
      derived from sporadic CCRCC, reexpression of VHL was found to restore E-cadherin
      expression. The product of the VHL gene has multiple reported functions, the best
      characterized of which is its role as the recognition component of an ubiquitin
      E3 ligase complex responsible for mediating oxygen-dependent destruction of
      hypoxia-inducible factor-alpha (HIF-alpha) subunits. We show that HIF activation
      is necessary and sufficient to suppress E-cadherin in renal cancer cells. Given
      the fundamental role of E-cadherin in controlling epithelial behavior, our
      findings give insight into how VHL inactivation/HIF activation may lead to kidney
      cancer and also indicate a mechanism by which reduced oxygenation could alter E
      cadherin expression in other cancers and influence normal homeostasis in other
      epithelia.

PMID- 16585182
TI  - Inactivation of conditional Rb by Villin-Cre leads to aggressive tumors outside
      the gastrointestinal tract.
AB  - We have crossed mice carrying the conditional Rb(tm2Brn) allele with a
      constitutive Villin-Cre transgenic mouse. The Villin promoter in these animals is
      highly expressed in adult intestine and kidney proximal tubules and is expressed
      in the gut and nephros anlagen during embryogenesis. We report here that these
      mice develop tumors between 12 and 17 months old outside the gastrointestinal
      (GI) tract. A high penetrance of pituitary tumors and medullar carcinoma of the
      thyroid is observed with a lower incidence of hyperplasia of pulmonary
      neuroendocrine cells and aggressive liver, bile duct, stomach, oral cavity
      tumors, and lipomas. Rb rearrangement due to ectopic Villin promoter activity in
      neural crest or neural crest stem cells during embryogenesis is most likely
      responsible for the medullar carcinoma of the thyroid phenotype. The aggressive
      nature of the medullar carcinoma of the thyroid and its ability to metastasize to
      unusual sites make the model suitable for the study of tumor progression and
      mechanism of metastasis. Observed sites of metastasis include the stomach, small
      intestine, liver, lung, kidney, pancreas, spleen, bone marrow, salivary gland,
      fat, lymph nodes, and dorsal root ganglion. Because the Villin promoter is highly
      active throughout the GI and in the nephros anlagen during development, we find
      that Rb inactivation is not sufficient to initiate tumorigenesis in the GI or
      kidneys in mice.

PMID- 16585183
TI  - Telomerase- and alternative telomere lengthening-independent telomere
      stabilization in a metastasis-derived human non-small cell lung cancer cell line:
      effect of ectopic hTERT.
AB  - In the majority of human malignancies, maintenance of telomeres is achieved by
      reactivation of telomerase, whereas a smaller fraction uses an alternative
      telomere lengthening (ALT) mechanism. Here, we used 16 non-small cell lung cancer
      (NSCLC) cell lines to investigate telomere stabilization mechanisms and their
      effect on tumor aggressiveness. Three of 16 NSCLC cell lines (VL-9, SK-LU-1, and
      VL-7) lacked telomerase activity, correlating with significantly reduced
      tumorigenicity in vitro and in vivo. Of the three telomerase-negative cell lines,
      only SK-LU-1 displayed characteristics of an ALT mechanism (i.e., highly
      heterogeneous telomeres and ALT-associated promyelocytic leukemia bodies). VL-9
      cells gained telomerase during in vitro propagation, indicating incomplete
      immortalization in vivo. In contrast, NSCLC metastasis-derived VL-7 cells
      remained telomerase and ALT negative up to high passage numbers and following
      transplantation in severe combined immunodeficient mice. Telomeres of VL-7 cells
      were homogeneously short, and chromosomal instability (CIN) was comparable with
      most telomerase-positive cell lines. This indicates the presence of an efficient
      telomere stabilization mechanism different from telomerase and ALT in VL-7 cells.
      To test the effect of ectopic telomerase reverse transcriptase (hTERT) in these
      unique ALT- and telomerase-negative tumor backgrounds, hTERT was transfected into
      VL-7 cells. The activation of telomerase led to an excessively rapid gain of
      telomeric sequences resulting in very long ( approximately 14 kb), uniform
      telomeres. Additionally, hTERT expression induced a more aggressive growth
      behavior in vitro and in vivo without altering the level of CIN. These data
      provide further evidence for a direct oncogenic activity of hTERT not based on
      the inhibition of CIN.

PMID- 16585185
TI  - A novel endocytic mechanism of epidermal growth factor receptor sequestration and
      internalization.
AB  - Cells form transient, circular dorsal ruffles or "waves" in response to
      stimulation of receptor tyrosine kinases, including epidermal growth factor
      receptor (EGFR) or platelet-derived growth factor receptor. These dynamic
      structures progress inward on the dorsal surface and disappear, occurring
      concomitantly with a marked reorganization of F-actin. The cellular function of
      these structures is largely unknown. Here we show that EGF-induced waves
      selectively sequester and internalize approximately 50% of ligand-bound EGFR from
      the cell surface. This process requires receptor phosphorylation, active
      phosphatidylinositol 3-kinase, and dynamin 2, although clathrin-coated pits or
      caveolae are not required. Epithelial and fibroblast cells stimulated with EGF
      sequestered EGFR rapidly into waves that subsequently generated numerous receptor
      positive tubular-vesicular structures. Electron microscopy confirmed that waves
      formed along the dorsal membrane surface and extended numerous tubules into the
      cytoplasm. These findings characterize a structure that selectively sequesters
      large numbers of activated EGFR for their subsequent internalization, independent
      of traditional endocytic mechanisms such as clathrin pits or caveolae.

PMID- 16585184
TI  - FoxM1B is overexpressed in human glioblastomas and critically regulates the
      tumorigenicity of glioma cells.
AB  - The transcription factor Forkhead box M1 (FoxM1) is overexpressed in malignant
      glioma. However, the functional importance of this factor in human glioma is not
      known. In the present study, we found that FoxM1B was the predominant FoxM1
      isoform expressed in human glioma but not in normal brain tissue. The level of
      FoxM1 protein expression in human glioma tissues was directly correlated with the
      glioma grade. The level of FoxM1 protein expression in human glioblastoma tissues
      was inversely correlated with patient survival. Enforced FoxM1B expression caused
      SW1783 and Hs683 glioma cells, which do not form tumor xenografts, to regain
      tumorigenicity in nude mouse model systems. Moreover, gliomas that arose from
      FoxM1B-transfected anaplastic astrocytoma SW1783 cells displayed glioblastoma
      multiforme phenotypes. Inhibition of FoxM1 expression in glioblastoma U-87MG
      cells suppressed their anchorage-independent growth in vitro and tumorigenicity
      in vivo. Furthermore, we found that FoxM1 regulates the expression of Skp2
      protein, which is known to promote degradation of the cell cycle regulator
      p27(Kip1). These results showed that FoxM1 is overexpressed in human
      glioblastomas and contributes to glioma tumorigenicity. Therefore, FoxM1 might be
      a new potential target of therapy for human malignant gliomas.

PMID- 16585186
TI  - Antibodies neutralizing hepsin protease activity do not impact cell growth but
      inhibit invasion of prostate and ovarian tumor cells in culture.
AB  - Hepsin is a type II transmembrane serine protease that is expressed in normal
      liver, and at lower levels in kidney, pancreas, and testis. Several studies have
      shown that hepsin mRNA is significantly elevated in most prostate tumors, as well
      as a significant fraction of ovarian and renal cell carcinomas and hepatomas.
      Although the overexpression of mRNA in these tumors has been extensively
      documented, there has been conflicting literature on whether hepsin plays a role
      in tumor cell growth and progression. Early literature implied a role for hepsin
      in human tumor cell proliferation, whereas recent studies with a transgenic mouse
      model for prostate cancer support a role for hepsin in tumor progression and
      metastases. To evaluate this issue further, we have expressed an activatable form
      of hepsin, and have generated a set of monoclonal antibodies that neutralize
      enzyme activity. The neutralizing antibodies inhibit hepsin enzymatic activity in
      biochemical and cell-based assays. Selected neutralizing and nonneutralizing
      antibodies were used in cell-based assays with tumor cells to evaluate the effect
      of antibodies on tumor cell growth and invasion. Neutralizing antibodies failed
      to inhibit the growth of prostate, ovarian, and hepatoma cell lines in culture.
      However, potent inhibitory effects of the antibodies were seen on invasion of
      ovarian and prostate cells in transwell-based invasion assays. These results
      support a role for hepsin in tumor cell progression but not in primary tumor
      growth. Consistent with this, immunohistochemical experiments with a mouse
      monoclonal antibody reveal progressively increased staining of prostate tumors
      with advanced disease, and in particular, extensive staining of bone metastatic
      lesions.

PMID- 16585187
TI  - Osteoprotegerin overexpression by breast cancer cells enhances orthotopic and
      osseous tumor growth and contrasts with that delivered therapeutically.
AB  - Osteoprotegerin (OPG) acts as a decoy receptor for receptor activator of NF
      kappaB ligand (RANKL), which is a pivotal molecule required for osteoclast
      formation. In vitro OPG inhibits osteoclast formation and in vivo (administered
      as Fc-OPG) it reduces hypercalcemia and the establishment of osteolytic lesions
      in mouse models of tumor cell growth in bone. Osteolysis can be induced by
      parathyroid hormone-related protein (PTHrP) produced by breast cancer cells that
      results in an increased osteoblastic RANKL/OPG ratio. We examined the effect of
      local tumor production of OPG on the ability of breast cancer cells to establish
      and grow in bone and mammary fat pad. MCF-7 cells or MCF-7 cells overexpressing
      PTHrP were transfected with full-length OPG and inoculated into the proximal
      tibiae of athymic nude mice. Mice injected with cells overexpressing PTHrP and
      OPG showed enhanced tumor growth, increased osteolysis (2-fold compared with MCF
      7 cells overexpressing PTHrP), and altered histology that was reflective of a
      less differentiated (more aggressive) phenotype compared with MCF-7 cells. In
      contrast, administration of recombinant Fc-OPG reduced tumor growth and limited
      osteolysis even in mice inoculated with OPG overexpressing cells. Similarly, OPG
      overexpression by breast cancer cells enhanced tumor growth following orthotopic
      inoculation. These results indicate that OPG overexpression by breast cancer
      cells increases tumor growth in vivo and that there are strikingly different
      responses between therapeutically administered Fc-OPG and full-length OPG
      produced by tumor cells.

PMID- 16585188
TI  - Cannibalism of live lymphocytes by human metastatic but not primary melanoma
      cells.
AB  - The phenomenon of cell cannibalism, which generally refers to the engulfment of
      cells within other cells, was described in malignant tumors, but its biological
      significance is still largely unknown. In the present study, we investigated the
      occurrence, the in vivo relevance, and the underlying mechanisms of cannibalism
      in human melanoma. As first evidence, we observed that tumor cannibalism was
      clearly detectable in vivo in metastatic lesions of melanoma and often involved T
      cells, which could be found in a degraded state within tumor cells. Then, in
      vitro experiments confirmed that cannibalism of T cells was a property of
      metastatic melanoma cells but not of primary melanoma cells. In particular,
      morphologic analyses, including time-lapse cinematography and electron
      microscopy, revealed a sequence of events, in which metastatic melanoma cells
      were able to engulf and digest live autologous melanoma-specific CD8(+) T cells.
      Importantly, this cannibalistic activity significantly increased metastatic
      melanoma cell survival, particularly under starvation condition, supporting the
      evidence that tumor cells may use the eating of live lymphocytes as a way to
      "feed" in condition of low nutrient supply. The mechanism underlying cannibalism
      involved a complex framework, including lysosomal protease cathepsin B activity,
      caveolae formation, and ezrin cytoskeleton integrity and function. In conclusion,
      our study shows that human metastatic melanoma cells may eat live T cells, which
      are instead programmed to kill them, suggesting a novel mechanism of tumor immune
      escape. Moreover, our data suggest that cannibalism may represent a sort of
      "feeding" activity aimed at sustaining survival and progression of malignant
      tumor cells in an unfavorable microenvironment.

PMID- 16585189
TI  - Targeted anti-vascular endothelial growth factor receptor-2 therapy leads to
      short-term and long-term impairment of vascular function and increase in tumor
      hypoxia.
AB  - Because antiangiogenic therapies inhibit the growth of new tumor-associated blood
      vessels, as well as prune newly formed vasculature, they would be expected to
      reduce the supply of oxygen and thus increase tumor hypoxia. However, it is not
      clear if antiangiogenic treatments lead only to consistent and sustained
      increases in hypoxia, or transient decreases in tumor hypoxia along with periods
      of increased hypoxia. We undertook a detailed analysis of an orthotopically
      transplanted human breast carcinoma (MDA-MB-231) over a 3-week treatment period
      using DC101, an anti-vascular endothelial growth factor receptor 2 antibody. We
      observed consistent reductions in microvascular density, blood flow (measured by
      high-frequency micro-ultrasound), and perfusion. These effects resulted in an
      increase in the hypoxic tumor fraction, measured with an exogenous marker,
      pimonidazole, concurrent with an elevation in hypoxia-inducible factor-1alpha
      expression, an endogenous marker. The increase in tumor hypoxia was evident
      within 5 days and remained so throughout the entire course of treatment. Vascular
      perfusion and flow were impaired at days 2, 5, 7, 8, 14, and 21 after the first
      injection, but not at 4 hours. A modest increase in the vessel maturation index
      was detected after the 3-week treatment period, but this was not accompanied by
      an improvement in vascular function. These results suggest that sustained hypoxia
      and impairment of vascular function can be two consistent consequences of
      antiangiogenic drug treatment. The implications of the results are discussed,
      particularly with respect to how they relate to different theories for the
      counterintuitive chemosensitizing effects of antiangiogenic drugs, even when
      hypoxia is increased.

PMID- 16585190
TI  - Signal transducer and activator of transcription 1 activation in endothelial
      cells is a negative regulator of angiogenesis.
AB  - To determine the role of the transcription factor signal transducer and activator
      of transcription (STAT) 1 on endothelial cell function, human umbilical vein
      endothelial cells (HUVEC) were treated with IFN-gamma, a potent activator of
      STAT1. IFN-gamma inhibited cell growth and tube formation of HUVECs. Although the
      potent proangiogenic protein vascular endothelial growth factor (VEGF) stimulated
      cell growth and tube formation, IFN-gamma could suppress these effects of VEGF.
      Transfection of HUVECs with short interfering RNA targeting STAT1 abrogated IFN
      gamma-induced inhibition of HUVEC growth and tube formation, and suppressed the
      inhibition of VEGF-induced tube formation by IFN-gamma, indicating that STAT1 is
      critical for this process. IFN-gamma blocks the biological activity of VEGF
      through inhibition of genes necessary for the VEGF response, including
      angiopoietin-2, urokinase plasminogen activator, tissue inhibitor of matrix
      metalloproteinase-1, cyclooxygenase-2, and VEGF receptor 2. To extend these
      findings in vivo, the role of STAT1 in angiogenesis was examined in STAT1
      deficient mice using the Matrigel in vivo angiogenesis assay. Substantial
      cellular infiltration and formation of vascular structures occurred in STAT1-/-
      mice compared with wild-type controls. These data indicate that STAT1 plays a key
      role in the inhibition of angiogenesis through its action within endothelial
      cells, and exploiting this process may be useful in treating cancers and vascular
      tumors.

PMID- 16585191
TI  - Immortalization of primary endothelial cells by the K1 protein of Kaposi's
      sarcoma-associated herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to three different human
      cancers: Kaposi's sarcoma, primary effusion lymphoma, and multicentric
      Castleman's disease. The Kaposi's sarcoma lesion expresses high levels of
      angiogenic factors and is comprised of a mixed cell population, including
      endothelial cells that are infected with KSHV. We find that the KSHV K1 protein
      is expressed in Kaposi's sarcoma lesions and can immortalize and extend the life
      span of primary human umbilical vein endothelial cells in culture. Vascular
      endothelial growth factor (VEGF) is critical for the survival of endothelial
      cells, and we show that expression of K1 in endothelial cells resulted in
      increased levels of secreted VEGF and the activation of key signaling pathways,
      including the VEGF/VEGF receptor and the phosphatidylinositol-3'-OH-kinase (PI3K)
      pathway. The SH2 binding motifs present in the cytoplasmic tail of K1 were
      critical for K1's ability to activate these pathways. Activation of PI3K by K1
      results in activation of Akt kinase and mammalian target of rapamycin and
      inactivation of the proapoptotic proteins FKHR, glycogen synthase kinase-3, and
      Bad, which are events indicative of cell survival. Because activation of the PI3K
      pathway is critical for transformation of many human cells, we suggest that PI3K
      activation by K1 is involved in endothelial cell immortalization and contributes
      to KSHV-associated tumorigenesis. We also report that K1 enhances angiogenesis in
      vivo and increases tumor vasculature and tumor size.

PMID- 16585192
TI  - Estrogen induces lung metastasis through a host compartment-specific response.
AB  - Direct proliferative effects of estrogen (E(2)) on estrogen receptor-positive
      tumors are well documented; however, the potential for E(2) to mediate effects
      selective for the host (i.e., angiogenesis, vascular permeability, or stromal
      effects), which influence tumor growth and/or metastasis, has received less
      attention. In this study, we examine the capacity for E(2) to promote tumor
      growth and/or metastasis independent of direct effects on tumor cells. In these
      studies, we distinguish host versus tumor compartment components of E(2) action
      in tumor growth and metastasis by analysis of E(2)-nonresponsive tumor cells
      implanted in ovariectomized (OVX) mice that contain s.c. implants of placebo
      (OVX) or E(2)-containing slow-release pellets (OVX + E(2)). We show that the D121
      lung carcinoma cell line is E(2)-nonresponsive, and following s.c. implantation
      in OVX versus OVX + E(2) mice, E(2) action on the host compartment leads to an
      increase in spontaneous metastasis but not primary tumor growth or
      neovascularization. Similarly, experimental lung metastasis of E(2)-nonresponsive
      4T1 mammary carcinoma cells also leads to increased tumor burden in the lungs of
      OVX + E(2) mice. These results suggest that the E(2) status of the host
      compartment influences late steps in tumor cell metastasis that can provide
      important insights into the role of E(2) in the tumor versus host compartments.

PMID- 16585193
TI  - High-resolution analysis of chromosomal breakpoints and genomic instability
      identifies PTPRD as a candidate tumor suppressor gene in neuroblastoma.
AB  - Although neuroblastoma is characterized by numerous recurrent, large-scale
      chromosomal imbalances, the genes targeted by such imbalances have remained
      elusive. We have applied whole-genome oligonucleotide array comparative genomic
      hybridization (median probe spacing 6 kb) to 56 neuroblastoma tumors and cell
      lines to identify genes involved with disease pathogenesis. This set of tumors
      was selected for having either 11q loss or MYCN amplification, abnormalities that
      define the two most common genetic subtypes of metastatic neuroblastoma. Our
      analyses have permitted us to map large-scale chromosomal imbalances and high
      level amplifications at exon-level resolution and to identify novel
      microdeletions and duplications. Chromosomal breakpoints (n = 467) generating
      imbalances >2 Mb were mapped to intervals ranging between 6 and 50 kb in size,
      providing substantial information on each abnormality. For example, breakpoints
      leading to large-scale hemizygous loss of chromosome 11q were highly clustered
      and preferentially associated with segmental duplications. High-level
      amplifications of MYCN were extremely complex, often resulting in a series of
      discontinuous regions of amplification. Imbalances (n = 540) <2 Mb long were also
      detected. Although the majority (78%) of these imbalances mapped to segmentally
      duplicated regions and primarily reflect constitutional copy number
      polymorphisms, many subtle imbalances were detected that are likely somatically
      acquired alterations and include genes involved with tumorigenesis, apoptosis, or
      neural cell differentiation. The most frequent microdeletion involved the PTPRD
      locus, indicating a possible tumor suppressor function for this gene.

PMID- 16585194
TI  - Gamma-secretase-dependent proteolysis of CD44 promotes neoplastic transformation
      of rat fibroblastic cells.
AB  - The metalloprotease-dependent extracellular domain cleavage of the adhesion
      molecule CD44 is frequently observed in human tumors and is thought to promote
      metastasis. This cleavage is followed by gamma-secretase-dependent release of
      CD44 intracellular domain (CD44-ICD), which exhibits nuclear signaling activity.
      Using a reversible Ret-dependent oncogenic conversion model and a restricted
      proteomic approach, we identified a positive correlation between the neoplastic
      transformation of Rat-1 cells and the expression of standard CD44. In these
      transformed cells, CD44 was found to undergo a sequential metalloprotease and
      gamma-secretase cleavage, resulting in an increase in expression of CD44-ICD. We
      showed that this proteolytic fragment possesses a transforming activity. In
      support of this role, a significant and specific reduction in Ret-induced
      transformation of Rat-1 cells was observed following drug-mediated inhibition of
      gamma-secretase. Taken together, these findings suggest that the shedding of CD44
      may not only modulate metastasis but also affects earlier events in tumorigenesis
      through the release of CD44-ICD.

PMID- 16585195
TI  - The oxygen sensor factor-inhibiting hypoxia-inducible factor-1 controls
      expression of distinct genes through the bifunctional transcriptional character
      of hypoxia-inducible factor-1alpha.
AB  - The function of the hypoxia-inducible factor-1 (HIF-1), the key transcription
      factor involved in cellular adaptation to hypoxia, is restricted to low oxygen
      tension (pO(2)). As such, this transcription factor is central in modulating the
      tumor microenvironment, sensing nutrient availability, and controlling anaerobic
      glycolysis, intracellular pH, and cell survival. Degradation and inhibition of
      the limiting HIF-1alpha subunit are intimately connected in normoxia.
      Hydroxylation of two proline residues by prolyl hydroxylase domain (PHD) 2
      protein earmarks the protein for degradation, whereas hydroxylation of an
      asparagine residue by factor-inhibiting HIF-1 (FIH-1 or FIH) reduces its
      transcriptional activity. Indeed, silencing of either PHD2 or FIH in normoxia
      partially induced hypoxic genes, whereas combined PHD2/FIH silencing generated a
      full hypoxic gene response. Given the fact that HIF-1alpha possesses two
      transcriptional activation domains [TAD; NH(2)-terminal (N-TAD) and COOH-terminal
      (C-TAD)], we hypothesized on a possible bifunctional activity of HIF-1alpha that
      could be discriminated by FIH, an inhibitor of the C-TAD. In human cell lines
      engineered to overexpress or silence FIH in response to tetracycline, we show by
      quantitative reverse transcription-PCR that a set of hypoxic genes (ca9, phd3,
      pgk1, and bnip3) respond differently toward FIH expression. This finding,
      extended to 26 hypoxia-induced genes, indicates differential gene expression by
      the N-TAD and C-TAD in response to the hypoxic gradient. We propose that the
      oxygen-sensitive attenuator FIH, together with two distinct TADs, is central in
      setting the gene expression repertoire dictated by the cell pO(2).

PMID- 16585196
TI  - Inactivation of von Hippel-Lindau gene induces constitutive phosphorylation of
      MET protein in clear cell renal carcinoma.
AB  - It is well known that inactivation of von Hippel-Lindau (VHL) gene predisposes
      for human clear cell renal carcinoma (CCRC). However, details about critical
      roles of VHL inactivation during tumorigenesis are still unknown. MET protein is
      a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF),
      which regulates cell growth, cell morphology, and cell motility. We showed that
      MET protein overexpressed in CCRC cells was phosphorylated without HGF/SF. This
      constitutive phosphorylation of MET protein in CCRC cells was inhibited by the
      rescue of exogenous wild-type VHL gene without a decrease in expression level of
      MET protein. Interestingly, wild-type VHL gene suppressed the phosphorylation of
      MET protein only under high cell density conditions. Additionally, MET protein
      activated by the inactivation of VHL gene modified cell adherence, including N
      cadherin and beta-catenin. When activation of MET protein in CCRC cells was
      inhibited by the MET inhibitor K252a, the growth of CCRC cells in vitro and the
      tumorigenesis induced by CCRC cells in nude mice were suppressed. From these
      results, we concluded that inactivation of VHL gene induced constitutive
      phosphorylation of MET protein and modified intercellular adherence structure to
      trigger the cell growth released from contact inhibition, finally resulting in
      tumorigenesis. This is one of the mechanisms of CCRC oncogenesis, and MET protein
      has potential as a molecular target for novel CCRC therapies.

PMID- 16585197
TI  - Estrogen up-regulates neuropeptide Y Y1 receptor expression in a human breast
      cancer cell line.
AB  - Normal breast tissue mainly expresses the neuropeptide Y (NPY) Y2 receptor
      whereas primary human breast carcinomas express the Y1 receptor (Y1R) subtype. We
      hypothesized that activation of estrogen signaling systems plays a role in the
      induction of Y1R. To investigate this possibility, we used estrogen receptor
      positive (ER+) human breast carcinoma cell line, MCF-7, and examined the effect
      of estrogen on Y1R gene expression and its signaling pathways. Saturation binding
      studies revealed that MCF-7 cells express high-affinity NPY receptor. NPY
      inhibited forskolin-stimulated adenosine 3'5'-cyclic monophosphate (cAMP)
      accumulation and mobilized intracellular Ca(2+) in MCF-7 cells. Chronic estrogen
      treatment enhanced NPY-mediated inhibition of cAMP accumulation by 4-fold and
      caused a significant increase in Y1R mRNA expression through ERalpha. Similarly,
      estrogen increased Y1R mRNA expression in T-47D (ER+) but not in MDA-MB231 or MDA
      MB468 (ER-) cell lines. Cycloheximide decreased basal Y1R mRNA expression;
      however, it did not affect its increase by estrogen. Moreover, estrogen treatment
      of MCF-7 cells did not increase Y1R mRNA stability. The up-regulation of Y1R
      expression by estrogen is prevented by hydroxyurea but not by nocodazole or IB
      MECA (cell cycle inhibitors). Lastly, NPY inhibited estrogen-induced cell
      proliferation through Y1R. In conclusion, MCF-7 cells express a functional Y1R
      coupled to both Ca(2+) and cAMP pathways. Estrogen up-regulates Y1R expression
      through ERalpha. This effect is independent of increased Y1R mRNA stability or
      new protein synthesis, and likely occurs during S phase completion of the cell
      cycle. Estrogen plays an important role in the up-regulation of Y1R, which in
      turn regulates estrogen-induced cell proliferation in breast cancer cells.

PMID- 16585198
TI  - ERBB2-mediated transcriptional up-regulation of the alpha5beta1 integrin
      fibronectin receptor promotes tumor cell survival under adverse conditions.
AB  - Oncogenic activation of the receptor tyrosine kinase ERBB2 is a key event in the
      development of a number of epithelial malignancies. In these tumors, high levels
      of ERBB2 are strongly associated with metastatic disease and poor prognosis.
      Paradoxically, an inherent cellular response to hypermitogenic signaling by ERBB2
      and other oncogenes seems to be growth arrest, rather than proliferation.
      Molecular characterization of this yet undefined antiproliferative state in
      independent cell lines overexpressing either wild-type ERBB2 or the mutationally
      activated receptor unveiled a dramatic induction of the alpha5beta1 integrin
      fibronectin receptor. alpha5 Integrin up-regulation is mainly a transcriptional
      response mediated by the hypoxia-inducible transcription factors (HIF), leading
      to a massive increase in membrane-resident receptor molecules and enhanced
      fibronectin adhesiveness of the respective cells. Functionally, ERBB2-dependent
      ligation of fibronectin results in improved survival of mammary adenocarcinoma
      cells under adverse conditions, like serum withdrawal, hypoxia, and chemotherapy.
      HIF-1alpha is an independent predictor of poor overall survival in patients with
      breast cancer. In particular, HIF-1alpha overexpression correlates significantly
      with early local relapse and distant metastasis, a phenotype also highly
      characteristic of ERBB2-positive tumors. As HIF-1alpha is known to be stabilized
      by ERBB2 signaling under normoxic conditions, we propose that alpha5 integrin is
      a major effector in this regulatory circuit and may represent the molecular basis
      for the HIF-1alpha-dependent aggressiveness observed in ERBB2-overexpressing
      breast carcinomas. Hypermitogenic ERBB2 signaling and tumor hypoxia may act
      synergistically to favor the establishment of chemoresistant dormant
      micrometastatic cells frequently observed in patients with breast cancer. This
      new insight could be the basis for additional approaches complementing current
      cancer therapy.

PMID- 16585199
TI  - Cyclooxygenase 2 rescues LNCaP prostate cancer cells from sanguinarine-induced
      apoptosis by a mechanism involving inhibition of nitric oxide synthase activity.
AB  - Expression of cyclooxygenase-2 (Cox-2), an inducible enzyme responsible for the
      production of prostaglandins from arachidonic acid, is elevated in human prostate
      tumor samples. The aim of this study was to investigate whether expression of Cox
      2 is effective against prostate cancer cell apoptosis triggered by sanguinarine,
      the quaternary benzophenanthridine alkaloid with antineoplastic properties.
      Sanguinarine effectively induced apoptosis in LNCaP human prostate cancer
      epithelial cells as assessed by caspase-3 activation assay, Annexin V staining
      assay, or by visual analysis for the apoptotic morphology changes. Sanguinarine
      mediated apoptosis was associated with the increase of nitric oxide (NO)
      formation in prostate cancer cells as assessed by measurements of nitrites with
      Sievers nitric oxide analyzer as well as flow cytometry analysis using NO
      fluorescent sensor. Activation of NO synthase (NOS) activity was crucial for
      sanguinarine-induced cell death because NOS inhibitor L-NMMA efficiently
      protected cells from apoptosis. Adenovirus-mediated transfer of Cox-2 into LNCaP
      cells inhibited sanguinarine-induced apoptosis and prevented an increase in NO
      production. Surprisingly, NO donors failed to induce apoptosis in LNCaP cells,
      suggesting that constitutive NO generation is not sufficient for triggering
      apoptosis in these cells. Besides NO generation, NOS is also capable of producing
      superoxide radicals. Sanguinarine-induced production of superoxide radicals, and
      the addition of MnTBAP, a scavenger of superoxide radicals, efficiently inhibited
      sanguinarine-mediated apoptosis. These results suggest that Cox-2 expression
      rescues prostate cancer cells from sanguinarine-induced apoptosis by a mechanism
      involving inhibition of NOS activity, and that coadministration of Cox-2
      inhibitors with sanguinarine may be developed as a strategy for the management of
      prostate cancer.

PMID- 16585200
TI  - Simultaneous inhibition of PDK1/AKT and Fms-like tyrosine kinase 3 signaling by a
      small-molecule KP372-1 induces mitochondrial dysfunction and apoptosis in acute
      myelogenous leukemia.
AB  - Phosphoinositol-3-kinase (PI3K)/protein kinase B (AKT) and Fms-like tyrosine
      kinase 3 (FLT3) signaling are aberrantly activated in acute myelogenous leukemia
      (AML) cells. Constitutively activated AKT and FLT3 regulate leukemia cell
      survival and resistance to chemotherapy. In this study, we investigated the
      effects of the novel multiple kinase inhibitor KP372-1 on the survival of AML
      cell lines and primary AML samples. KP372-1 directly inhibited the kinase
      activity of AKT, PDK1, and FLT3 in a concentration-dependent manner. Western blot
      analysis indicated that KP372-1 decreased the phosphorylation of AKT on both
      Ser(473) and Thr(308); abrogated the phosphorylation of p70S6 kinase, BAD, and
      Foxo3a via PI3K/AKT signaling; and down-regulated expression of PIM-1 through
      direct inhibition of FLT3. Treatment of AML cell lines with KP372-1 resulted in
      rapid generation of reactive oxygen species and stimulation of oxygen
      consumption, followed by mitochondrial depolarization, caspase activation, and
      phosphatidylserine externalization. KP372-1 induced pronounced apoptosis in AML
      cell lines and primary samples irrespective of their FLT3 status, but not in
      normal CD34(+) cells. Moreover, KP372-1 markedly decreased the colony-forming
      ability of primary AML samples (IC(50) < 200 nmol/L) with minimal cytotoxic
      effects on normal progenitor cells. Taken together, our results show that the
      simultaneous inhibition of critical prosurvival kinases by KP372-1 leads to
      mitochondrial dysfunction and apoptosis of AML but not normal hematopoietic
      progenitor cells.

PMID- 16585201
TI  - Improvement of the tumor-suppressive effect of boron neutron capture therapy for
      amelanotic melanoma by intratumoral injection of the tyrosinase gene.
AB  - Boron neutron capture therapy (BNCT) is successful when there is a sufficient
      (10)B concentration in tumor cells. In melanoma, (10)B-para-boronophenylalanine
      (BPA) accumulation is proportional to melanin-producing activity. This study was
      done to confirm enhancement of the tumor-suppressive effect of BNCT on amelanotic
      melanoma by intratumoral injection of the tyrosinase gene. D178 or FF amelanotic
      melanomas were implanted s.c. in Syrian hamsters. One group of D178- or FF
      bearing hamsters (TD178 or TFF group) received intratumoral injections of pcDNA
      Tyrs constructed as a tyrosinase expression plasmid. The other hamsters (pD178
      and pFF groups) were injected with pUC119, and control hamsters (D178 and FF
      groups) only with transfection reagents. All the groups underwent
      immunofluorescence analysis of tyrosinase expression and BPA biodistribution
      studies. BNCT experiments were done at the Kyoto University Research Reactor.
      Tyrosinase expression increased in the tumors of the TD178 and TFF groups but
      remained the same in the pD178 and pFF groups. Tumor boron concentrations in the
      TD178 and TFF groups increased significantly (TD178: 49.7 +/- 12.6 versus D178:
      27.2 +/- 4.9 microg/g, P < 0.0001; TFF: 30.7 +/- 6.6 versus FF: 13.0 +/- 4.7
      microg/g, P < 0.0001). The BNCT tumor-suppressive effect was marked in the TD178
      and TFF groups. In vivo transfection with the tyrosinase gene increased BPA
      accumulation in the tumors, the BNCT tumor-suppressive effect on amelanotic
      melanoma being significantly enhanced. These findings suggest a potential new
      clinical strategy for the treatment of amelanotic melanoma with BNCT.

PMID- 16585202
TI  - Ubiquitin-proteasome system stress sensitizes ovarian cancer to proteasome
      inhibitor-induced apoptosis.
AB  - The ubiquitin-proteasome system (UPS) mediates targeted protein degradation.
      Notably, the UPS determines levels of key checkpoint proteins controlling
      apoptosis and proliferation by controlling protein half-life. Herein, we show
      that ovarian carcinoma manifests an overstressed UPS by comparison with normal
      tissues by accumulation of ubiquitinated proteins despite elevated proteasome
      levels. Elevated levels of total ubiquitinated proteins and 19S and 20S
      proteasome subunits are evident in both low-grade and high-grade ovarian
      carcinoma tissues relative to benign ovarian tumors and in ovarian carcinoma cell
      lines relative to immortalized surface epithelium. We find that ovarian carcinoma
      cell lines exhibit greater sensitivity to apoptosis in response to proteasome
      inhibitors than immortalized ovarian surface epithelial cells. This sensitivity
      correlates with increased cellular proliferation rate and UPS stress rather than
      absolute proteasome levels. Proteasomal inhibition in vitro induces cell cycle
      arrest and the accumulation of p21 and p27 and triggers apoptosis via activation
      of caspase-3. Furthermore, treatment with the licensed proteasome inhibitor PS
      341 slows the growth of ES-2 ovarian carcinoma xenograft in immunodeficient mice.
      In sum, elevated proliferation and metabolic rate resulting from malignant
      transformation of the epithelium stresses the UPS and renders ovarian carcinoma
      more sensitive to apoptosis in response to proteasomal inhibition.

PMID- 16585203
TI  - Selective inhibition of ErbB2-overexpressing breast cancer in vivo by a novel TAT
      based ErbB2-targeting signal transducers and activators of transcription 3
      blocking peptide.
AB  - ErbB2 is an excellent target for cancer therapies. Unfortunately, the outcome of
      current therapies for ErbB2-positive breast cancers remains unsatisfying due to
      resistance and side effects. New therapies for ErbB2-overexpressing breast
      cancers continue to be in great need. Peptide therapy using cell-penetrating
      peptides (CPP) as peptide carriers is promising because the internalization is
      highly efficient, and the cargoes delivered can be bioactive. However, the major
      obstacle in using these powerful CPPs for therapy is their lack of specificity.
      Here, we sought to develop a peptide carrier that could introduce therapeutics
      specifically to ErbB2-overexpressing breast cancer cells. By modifying the HIV
      TAT-derived CPP and conjugating anti-HER-2/neu peptide mimetic (AHNP), we
      developed the peptide carrier (P3-AHNP) that specifically targeted ErbB2
      overexpressing breast cancer cells in vitro and in vivo. A signal transducers and
      activators of transcription 3 (STAT3)-inhibiting peptide conjugated to this
      peptide carrier (P3-AHNP-STAT3BP) was delivered more efficiently into ErbB2
      overexpressing than ErbB2 low-expressing cancer cells in vitro and successfully
      decreased STAT3 binding to STAT3-interacting DNA sequence. P3-AHNP-STAT3BP
      inhibited cell growth in vitro, with ErbB2-overexpressing 435.eB breast cancer
      cells being more sensitive to the treatment than the ErbB2 low-expressing MDA-MB
      435 cells. Compared with ErbB2 low-expressing MDA-MB-435 xenografts, i.p.
      injected P3-AHNP-STAT3BP preferentially accumulated in 435.eB xenografts, which
      led to more reduction of proliferation and increased apoptosis and targeted
      inhibition of tumor growth. This novel peptide delivery system provided a sound
      basis for the future development of safe and effective new-generation
      therapeutics to cancer-specific molecular targets.

PMID- 16585204
TI  - Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in
      pancreatic cancer cells.
AB  - The proteasome inhibitor bortezomib (formerly known as PS-341) recently received
      Food and Drug Administration approval for the treatment of multiple myeloma, and
      its activity is currently being evaluated in solid tumors. Bortezomib triggers
      apoptosis in pancreatic cancer cells, but the mechanisms involved have not been
      fully elucidated. Here, we show that pancreatic cancer cells exposed to
      bortezomib formed aggregates of ubiquitin-conjugated proteins ("aggresomes") in
      vitro and in vivo. Bortezomib-induced aggresome formation was determined to be
      cytoprotective and could be disrupted using histone deacetylase (HDAC) 6 small
      interfering RNA or chemical HDAC inhibitors, which resulted in endoplasmic
      reticulum stress and synergistic levels of apoptosis in vitro and in an
      orthotopic pancreatic cancer xenograft model in vivo. Interestingly, bortezomib
      did not induce aggresome formation in immortalized normal human pancreatic
      epithelial cells in vitro or in murine pancreatic epithelial cells in vivo. In
      addition, these cells did not undergo apoptosis following treatment with
      bortezomib, suberoylanilide hydroxamic acid, or the combination, showing tumor
      selectivity. Taken together, our study shows that inhibition of aggresome
      formation can strongly potentiate the efficacy of bortezomib and provides the
      foundation for clinical trials of bortezomib in combination with HDAC inhibitors
      for the treatment of pancreatic cancer.

PMID- 16585205
TI  - Rational design of the microtubule-targeting anti-breast cancer drug EM015.
AB  - We studied in silico docking of noscapine onto tubulin, combined with
      calculations of surface charge, pi-pi, van der Waals, and hydrogen bonding
      interactions, to rationally design a new compound, EM015. This tubulin-binding
      semisynthetic compound is a selective and potent anti-breast cancer agent and
      displays a 20-fold lower IC(50) against many tumor cells compared with our
      founding compound, (S)-6,7-dimethoxy-3-((R)-4-methoxy-6-methyl-5,6,7,8
      tetrahydro[1,3]-dioxolo-[4,5-g]isoquinolin-5-yl)isobenzo-furan-1(3H)-one
      (noscapine). Furthermore, EM015 is also effective against a variety of drug
      resistant cells. Surprisingly, the cell cycle profile of nontumorigenic normal
      cells is not affected. Many antimicrotubule cancer drugs in clinic today,
      particularly taxanes and Vincas, face challenges including frequent visits to the
      hospital for prolonged i.v. infusions, toxicities, and tumor recurrences due to
      drug resistance. EM015, on the other hand, is orally available, regresses breast
      tumor xenografts in nude mice models, and increases longevity. Furthermore, we
      have failed to observe any detectable toxicity in tissues, such as liver, kidney,
      spleen, lung, heart, and brain, as well as neurons, which are common targets of
      antimicrotubule drug therapy. Thus, EM015 has a great promise in the clinic.

PMID- 16585206
TI  - The influence of a human embryonic stem cell-derived microenvironment on
      targeting of human solid tumor xenografts.
AB  - The awareness of the important role that the surrounding tissue microenvironment
      and stromal response play in the process of tumorigenesis has grown as a result
      of in vivo models of tumor xenograft growth in immunocompromised mice. In the
      current study, we used human embryonic stem cells in order to study the
      interactions of tumor cells with the surrounding microenvironment of
      differentiated human cell tissues and structures. Several cancer cell types
      stably expressing an H2A-green fluorescence protein fusion protein, which allowed
      tracking of tumor cells, were injected into mature teratomas and developed into
      tumors. The salient findings were: (a) the observation of growth of tumor cells
      with high proliferative capacity within the differentiated microenvironment of
      the teratoma, (b) the identification of invasion by tumor cells into surrounding
      differentiated teratoma structures, and (c) the identification of blood vessels
      of human teratoma origin, growing adjacent to and within the cancer cell-derived
      tumor. Mouse embryonic stem cell-derived teratomas also supported cancer cell
      growth, but provided a less suitable model for human tumorigenesis studies.
      Anticancer immunotherapy treatment directed against A431 epidermoid carcinoma
      cell-related epitopes induced the complete regression of A431-derived tumor
      xenografts following direct i.m. injection in immunocompromised mice, as opposed
      to corresponding tumors growing within a human embryonic stem cell-derived
      microenvironment, wherein remnant foci of viable tumor cells were detected and
      resulted in tumor recurrence. We propose using this novel experimental model as a
      preclinical platform for investigating and manipulating the stromal response in
      tumor cell growth as an additional tool in cancer research.

PMID- 16585207
TI  - Transforming growth factor alpha expression drives constitutive epidermal growth
      factor receptor pathway activation and sensitivity to gefitinib (Iressa) in human
      pancreatic cancer cell lines.
AB  - The epidermal growth factor receptor (EGFR) is considered an important
      therapeutic target in pancreatic cancer, but it is currently impossible to
      identify those patients who are most likely to benefit from EGFR-directed
      therapy. We examined the biological effects of the EGFR tyrosine kinase inhibitor
      gefitinib (ZD1839, Iressa) in a panel of nine human pancreatic cancer cell lines.
      The drug strongly inhibited DNA synthesis and induced low levels of apoptosis at
      clinically relevant concentrations in a subset of three of the lines (L3.6pl,
      BxPC3, and Cfpac1). Sensitivity to gefitinib correlated directly with ligand
      [transforming growth factor-alpha (TGF-alpha)] expression (r(2) = 0.71, P =
      0.004) but not with surface EGFR expression. The gefitinib-sensitive cells
      displayed constitutive baseline EGFR phosphorylation, whereas the gefitinib
      resistant cells did not. Exposure to gefitinib or a small interfering RNA
      construct specific for TGF-alpha reversed the constitutive EGFR phosphorylation
      and downstream target [extracellular signal-regulated kinases (ERK), AKT]
      phosphorylation in the gefitinib-sensitive cells but had no effects on ERK or AKT
      phosphorylation in gefitinib-resistant cells. Baseline EGFR phosphorylation was
      lower in a subclone of L3.6pl selected for low TGF-alpha expression, and these
      cells were also resistant to gefitinib-mediated growth inhibition. Gefitinib
      blocked the growth of tumor xenografts derived from L3.6pl cells but had no
      effect on the growth of tumors derived from EGFR-independent MiaPaCa-2 cells.
      Together, our data show that TGF-alpha expression identifies a subset of human
      pancreatic cancer cells that is dependent on EGFR signaling in vitro and in vivo.
      Quantification of TGF-alpha expression may therefore represent an effective means
      of identifying EGFR-responsive primary tumors.

PMID- 16585208
TI  - Testicular xenografts: a novel approach to study cytotoxic damage in juvenile
      primate testis.
AB  - The underlying primary damage to the testis caused by chemotherapeutic regimens
      during childhood is largely unknown. Xenografting of monkey testes was
      successfully applied in maturation of juvenile testis to the point of complete
      spermatogenesis. This allows us to manipulate developing primate testis without
      direct treatment of patients. This new model is validated establishing the
      effects of cytotoxic treatment in the immature primate testis. Male castrated
      nude mice received eight s.c. grafts of juvenile monkey testicular tissue and, 28
      weeks later, were injected with busulfan (38 mg/kg, i.p.) or vehicle. Graft
      numbers, size, and histology were examined. Grafts showed pubertal induction of
      spermatogenesis to the level of pachytene spermatocytes at point of busulfan
      treatment and further progressed to the level of round spermatids in control
      samples at 4 weeks. Busulfan treatment caused a statistically significant
      decrease in the number of seminiferous tubules containing germ cells. Type B
      spermatogonia and more advanced stages of spermatogenesis were depleted. A
      statistically significant decrease to pretreatment level was observed in the
      number of type A pale and centrally located spermatogonia. Busulfan did not
      affect type A dark spermatogonia. Occasionally, elongating spermatids were
      detected in busulfan-treated grafts. Observations show that busulfan selectively
      destroys differentiating spermatogonia whereas some of the spermatocytes present
      at the moment of cytotoxic insult are able to continue differentiation. Data
      indicate that xenografting of testicular monkey tissue is a valid approach to
      detect the busulfan-induced germ cell damage and serves as a powerful
      experimental tool to study cytotoxic effects in developing primate testis.

PMID- 16585209
TI  - Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic
      carcinoma.
AB  - Aberrant patterns of pre-mRNA splicing have been established for many human
      malignancies, yet the mechanisms responsible for these tumor-specific changes
      remain undefined and represent a promising area for therapeutic intervention.
      Using immunohistochemistry, we have localized the expression of a central
      splicing regulator, serine-arginine protein kinase 1 (SRPK1), to the ductular
      epithelial cells within human pancreas and have further shown its increased
      expression in tumors of the pancreas, breast, and colon. Small interfering RNA
      mediated down-regulation of SRPK1 in pancreatic tumor cell lines resulted in a
      dose-dependent decrease in proliferative capacity and increase in apoptotic
      potential. Coordinately, the disruption of SRPK1 expression resulted in enhanced
      sensitivity of tumor cells to killing by gemcitabine and/or cisplatin. A dose
      dependent reduction in the phosphorylation status of specific SR proteins was
      detected following the down-regulation of SRPK1 and is likely responsible for the
      observed alterations in expression of proteins associated with apoptosis and
      multidrug resistance. These data support SRPK1 as a new, potential target for the
      treatment of pancreatic ductular cancer that at present remains largely
      unresponsive to conventional therapies. Furthermore, these results support the
      development of innovative therapies that target not only specific splice variants
      arising during tumorigenesis but also the splice regulatory machinery that itself
      may be abnormal in malignant cells.

PMID- 16585210
TI  - Targeting PIM kinases impairs survival of hematopoietic cells transformed by
      kinase inhibitor-sensitive and kinase inhibitor-resistant forms of Fms-like
      tyrosine kinase 3 and BCR/ABL.
AB  - Previous studies have shown that activation of the signal transducer and
      activator of transcription 5 (STAT5) plays an essential role in leukemogenesis
      mediated through constitutive activated protein tyrosine kinases (PTK). Because
      PIM-1 is a STAT5 target gene, we analyzed the role of the family of PIM
      serine/threonine kinases (PIM-1 to PIM-3) in PTK-mediated transformation of
      hematopoietic cells. Ba/F3 cells transformed to growth factor independence by
      various oncogenic PTKs (TEL/JAK2, TEL/TRKC, TEL/ABL, BCR/ABL, FLT3-ITD, and
      H4/PDGFbetaR) show abundant expression of PIM-1 and PIM-2. Suppression of PIM-1
      activity had a negligible effect on transformation. In contrast, expression of
      kinase-dead PIM-2 mutant (PIM-2KD) led to a rapid decline of survival in Ba/F3
      cells transformed by FLT3-ITD but not by other oncogenic PTKs tested.
      Coexpression of PIM-1KD and PIM-2KD abrogated growth factor-independent growth of
      Ba/F3 transformed by several PTKs, including BCR/ABL. Targeted down-regulation of
      PIM-2 by RNA interference (RNAi) selectively abrogated survival of Ba/F3 cells
      transformed by various Fms-like tyrosine kinase 3 (FLT3)-activating mutants
      [internal tandem duplication (ITD) and kinase domain] and attenuated growth of
      human cell lines containing FLT3 mutations. Interestingly, cells transformed by
      FLT3 and BCR/ABL mutations that confer resistance to small-molecule tyrosine
      kinase inhibitors were still sensitive to knockdown of PIM-2, or PIM-1 and PIM-2
      by RNAi. Our observations indicate that combined inactivation of PIM-1 and PIM-2
      interferes with oncogenic PTKs and suggest that PIMs are alternative therapeutic
      targets in PTK-mediated leukemia. Targeting the PIM kinase family could provide a
      new avenue to overcome resistance against small-molecule tyrosine kinase
      inhibitors.

PMID- 16585211
TI  - 5-amino-4-imidazolecarboxamide riboside potentiates both transport of reduced
      folates and antifolates by the human reduced folate carrier and their subsequent
      metabolism.
AB  - Transport is required before reduced folates and anticancer antifolates [e.g.,
      methotrexate (MTX)] exert their physiologic functions or cytotoxic effects. The
      folate/antifolate transporter with the widest tissue distribution and greatest
      activity is the reduced folate carrier (RFC). There is little evidence that RFC
      mediated influx is posttranscriptionally regulated. We show that [(3)H]MTX influx
      in CCRF-CEM human childhood T-leukemia cells is potentiated up to 6-fold by
      exogenous 5-amino-4-imidazolecarboxamide riboside (AICAr) in a AICAr and MTX
      concentration-dependent manner. Metabolism to more biologically active
      polyglutamate forms is also potentiated for MTX and other antifolates. That
      potentiation of influx by AICAr is mediated by effects on the RFC is supported by
      analyses +/-AICAr showing (a) similarity and magnitude of kinetic constants for
      [(3)H]MTX influx; (b) similarity of inhibitory potency of known RFC substrates;
      (c) lack of potentiation in a CCRF-CEM subline that does not express the RFC; and
      (d) similarity of time and temperature dependence. Potentiation occurs rapidly
      and does not require new protein synthesis. Effects of specific inhibitors of
      folate metabolism and the time and sequence of AICAr incubation with cells
      suggest that both dihydrofolate reductase inhibition and metabolism of AICAr are
      essential for potentiation. Acute folate deficiency or incubation of CCRF-CEM
      with AICAr-related metabolites (e.g., adenosine) does not initiate potentiation.
      AICAr increases growth inhibitory potency of MTX and aminopterin against CCRF-CEM
      cells when both AICAr and antifolate are present for the first 24 hours of a 120
      hour growth period. AICAr is the first small molecule that regulates RFC
      activity.

PMID- 16585212
TI  - Hydroxyurea induces bystander cytotoxicity in cocultures of herpes simplex virus
      thymidine kinase-expressing and nonexpressing HeLa cells incubated with
      ganciclovir.
AB  - Suicide gene therapy with the herpes simplex virus thymidine kinase (HSV-TK) cDNA
      and ganciclovir can elicit cytotoxicity to transgene-expressing and nonexpressing
      bystander cells via transfer of ganciclovir phosphates through gap junctions.
      HeLa cells do not exhibit bystander cytotoxicity, although we showed recently
      that they transfer low levels of ganciclovir phosphates to bystander cells. Here,
      we attempted to induce bystander cytotoxicity using hydroxyurea, an inhibitor of
      ribonucleotide reductase, to decrease the endogenous dGTP pool, which should
      lessen competition with ganciclovir triphosphate for DNA incorporation. Addition
      of hydroxyurea to cocultures of HSV-TK-expressing and bystander cells
      synergistically increased ganciclovir-mediated cytotoxicity to both cell
      populations while producing primarily an additive effect in cultures of 100% HSV
      TK-expressing cells. Whereas HSV-TK-expressing cells in coculture were
      approximately 50-fold less sensitive to ganciclovir compared with cultures of
      100% HSV-TK-expressing cells, addition of hydroxyurea restored ganciclovir
      sensitivity. Quantification of deoxynucleoside triphosphate pools showed that
      hydroxyurea decreased dGTP pools without significantly affecting ganciclovir
      triphosphate levels. Although hydroxyurea significantly increased the ganciclovir
      triphosphate:dGTP value for 12 to 24 hours in HSV-TK-expressing and bystander
      cells from coculture (1.4- to 4.9-fold), this value was increased for <12 hours
      (2.5-fold) in 100% HSV-TK-expressing cells. These data suggest that the prolonged
      increase in the ganciclovir triphosphate:dGTP value in cells in coculture
      resulted in synergistic cytotoxicity. Compared with enhancement of bystander
      cytotoxicity through modulation of gap junction intercellular communication, this
      strategy is superior because it increased cytotoxicity to both HSV-TK-expressing
      and bystander cells in coculture. This approach may improve clinical efficacy.

PMID- 16585213
TI  - Regeneration and tolerance factor: a novel mediator of glioblastoma-associated
      immunosuppression.
AB  - Regeneration and tolerance factor (RTF) was originally identified in placenta
      where it is thought to be essential for fetal allograft survival. Here we report
      that RTF mRNA and protein are also expressed in human glioma cells in vitro and
      in vivo. Suppression of RTF expression by RNA interference promotes the lysis of
      glioma cells by natural killer (NK) and T cells in vitro. Moreover, RTF-depleted
      glioma cells are less tumorigenic than control cells in nude mice in vivo.
      Depletion of NK cells in these animals abolished this effect. RTF is thus a novel
      aberrantly expressed molecule which confers immune privilege to human malignant
      gliomas.

PMID- 16585214
TI  - TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian
      cancer.
AB  - Evidence suggests that an inflammatory profile of cytokines and chemokines
      persisting at a particular site would lead to the development of a chronic
      disease. Recent studies implicate bacterial infection as one possible link
      between inflammation and carcinogenesis; however, the crucial molecular pathways
      involved remain unknown. We hypothesized that one possible upstream signaling
      pathway leading to inflammation in carcinogenesis may be mediated by Toll-like
      receptors (TLR). We describe for the first time an adaptive mechanism acquired by
      ovarian cancer cells that allows them to promote a proinflammatory environment
      and develop chemoresistance. We propose that the TLR-4-MyD88 signaling pathway
      may be a risk factor for developing cancer and may represent a novel target for
      the development of biomodulators. Our work explains how bacterial products, such
      as lipopolysaccharide, can promote, directly from the tumor, the production of
      proinflammatory cytokines and the enhancement of tumor survival. In addition, we
      provide new evidence that links TLR-4 signaling, inflammation, and
      chemoresistance in ovarian cancer cells.

PMID- 16585215
TI  - CD1d-restricted natural killer T cells can down-regulate tumor immunosurveillance
      independent of interleukin-4 receptor-signal transducer and activator of
      transcription 6 or transforming growth factor-beta.
AB  - It has been shown previously that the suppression of tumor immunosurveillance may
      be a mechanism by which tumors resist immune detection and elimination. In this
      study, we evaluated the role of the immunoregulatory natural killer T (NKT) cells
      in the biology of immunosurveillance of osteosarcoma. The K7M2 mouse osteosarcoma
      cell line was implanted orthotopically into wild-type and NKT cell-deficient CD1d
      knockout (KO) BALB/c mice, and mice were monitored for growth of primary tumors.
      Further, we examined the role of CD4(+) and/or CD8(+) cells by depleting the
      cells in vivo and measuring CTL activity in vitro. We also asked the role of
      interleukin (IL)-4 receptor alpha (IL-4Ralpha)-signal transducer and activator of
      transcription 6 (STAT6) signaling, including IL-13, and transforming growth
      factor beta (TGF-beta) by using gene-disrupted mice or treating mice with
      cytokine antagonists. We were surprised to find a high rate of rejection of
      osteosarcoma primary tumors in 88% (14 of 16) of CD1d KO mice compared with
      syngeneic wild-type BALB/c mice that showed rejection of tumor in <24% of mice.
      Further studies suggested that the rejection of tumor in CD1d KO mice was
      dependent on CD8(+) lymphocytes. Distinct from other murine tumor models, the
      negative regulation induced by CD1d-restricted NKT cells was not dependent on IL
      4Ralpha-STAT6 signaling, including IL-13, or on TGF-beta. These data suggest that
      a novel CD1d-restricted NKT cell-mediated mechanism for tumor immunosuppression
      is active in the K7M2 osteosarcoma model and that NKT cells can regulate
      immunosurveillance through more than one pathway.

PMID- 16585216
TI  - Complement activated by chimeric anti-folate receptor antibodies is an efficient
      effector system to control ovarian carcinoma.
AB  - Two chimeric monoclonal antibodies (mAb), cMOV18 and cMOV19, recognizing distinct
      epitopes of folate receptor highly expressed on epithelial ovarian cancer (EOC)
      cells were analyzed for their ability to activate complement (C) as a means to
      enhance their antitumor activity. The individual cMOVs failed to activate C on
      six EOC cell lines as documented by the marginal deposition of C components and
      the negligible C-dependent cytotoxicity (CDC). Conversely, the mixture of cMOVs
      was more effective, although the percentage of cell killing did not exceed 25%.
      Fluorescence-activated cell sorting analysis of EOC cells for surface expression
      of the membrane C regulatory proteins (mCRP) revealed high levels of CD46,
      variable expression of CD59, and absence of CD55. This finding was confirmed in
      tumor tissue specimens obtained from advanced-stage EOC patients and analyzed for
      the expression of mCRPs mRNA using a cDNA microarray and for the presence of
      proteins by immunohistochemistry. Incubation of EOC cells with neutralizing mAbs
      to CD46 and CD59 led to a significant increase in the CDC from 10%-20% to 45%
      50%. The relative contribution of antibody-dependent cell cytoxicity (ADCC) and C
      dependent killing of two EOC cell lines induced by the mixture of cMOV18 and
      cMOV19 was about 15% and 25%-35%, respectively, bringing the total killing to
      about 40%-50%. This value increased to 60%-70% after neutralization of CD46 and
      CD59 without an appreciable change of ADCC. These results suggest that C is the
      major contributor to the killing of EOC cells induced by the mixture of cMOV18
      and cMOV19.

PMID- 16585217
TI  - A genetically engineered anti-CD45 single-chain antibody-streptavidin fusion
      protein for pretargeted radioimmunotherapy of hematologic malignancies.
AB  - Acute myelogenous leukemia (AML) currently kills the majority of afflicted
      patients despite combination chemotherapy and hematopoietic cell transplantation
      (HCT). Our group has documented the promise of radiolabeled anti-CD45 monoclonal
      antibodies (Ab) administered in the setting of allogeneic HCT for AML, but
      toxicity remains high, and cure rates are only 25% to 30% for relapsed AML. We
      now show the superiority of pretargeted radioimmunotherapy (PRIT) compared with
      conventional radioimmunotherapy using a recombinant tetravalent single-chain Ab
      streptavidin (SA) fusion protein (scFv(4)SA) directed against human CD45,
      administered sequentially with a dendrimeric N-acetylgalactosamine-containing
      clearing agent and radiolabeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''
      tetraacetic (DOTA)-biotin. The scFv(4)SA construct was genetically engineered by
      fusing Fv fragments of the human CD45-specific BC8 Ab to a full-length genomic SA
      gene and was expressed as a soluble tetramer in the periplasmic space of
      Escherichia coli. The fusion protein was purified to >95% homogeneity at an
      overall yield of approximately 50% using iminobiotin affinity chromatography. The
      immunoreactivity and avidity of the fusion protein were comparable with those of
      the intact BC8 Ab, and the scFv(4)SA construct bound an average of 3.9 biotin
      molecules out of four theoretically possible. Mouse lymphoma xenograft
      experiments showed minimal toxicity, excellent tumor-specific targeting of the
      fusion protein and radiolabeled DOTA-biotin in vivo, marked inhibition of tumor
      growth, and cured 100% of mice bearing CD45-expressing tumors. These promising
      results have prompted large-scale cGMP production of the BC8 fusion protein for
      clinical trials to be conducted in patients with hematologic malignancies.

PMID- 16585218
TI  - The transcription factor ZEB1 is aberrantly expressed in aggressive uterine
      cancers.
AB  - The transcription factor ZEB1 (deltaEF1 in mice) has been implicated in cellular
      processes during development and tumor progression including epithelial to
      mesenchymal transition. deltaEF1 null mice die at birth, but heterozygotes
      expressing a LacZ reporter inserted into the deltaEF1 gene live and reproduce.
      Using these mice, we observed ZEB1 promoter activity in the virgin myometrium,
      and stroma and myometrium of the pregnant uterus. ZEB1 protein is up-regulated in
      the myometrium and endometrial stroma after progesterone or estrogen treatment of
      ovariectomized mice. In the normal human uterus, ZEB1 protein is increased in the
      myometrium and stroma during the secretory stage of the menstrual cycle. ZEB1 is
      not expressed in the normal endometrial epithelium. In malignancies of the
      uterus, we find that ZEB1 (a) is overexpressed in malignant tumors derived from
      the myometrium (leiomyosarcomas), (b) is overexpressed in tumor-associated stroma
      of low-grade endometrioid adenocarcinomas, and (c) is aberrantly expressed in the
      tumor epithelial cells of aggressive endometrial cancers. Specifically, in grade
      3 endometrioid adenocarcinomas and uterine papillary serous carcinomas, ZEB1
      could be expressed in the epithelial-derived carcinoma cells as well as in the
      stroma. In malignant mixed Mullerian tumors, the sarcomatous component always
      expresses ZEB1, and the carcinomatous component can also be positive. In summary,
      ZEB1 is normally regulated by both estrogen and progesterone receptors, but in
      uterine cancers, it is likely no longer under control of steroid hormone
      receptors and becomes aberrantly expressed in epithelial-derived tumor cells,
      supporting a role for ZEB1 in epithelial to mesenchymal transitions associated
      with aggressive tumors.

PMID- 16585219
TI  - Activation of mitogen-activated protein kinase in estrogen receptor alpha
      positive breast cancer cells in vitro induces an in vivo molecular phenotype of
      estrogen receptor alpha-negative human breast tumors.
AB  - Breast cancer presents as either estrogen receptor alpha (ERalpha) positive or
      negative, with ERalpha+ tumors responding to antiestrogen therapy and having a
      better prognosis. By themselves, mRNA expression signatures of estrogen
      regulation in ERalpha+ breast cancer cells do not account for the vast molecular
      differences observed between ERalpha+ and ERalpha- cancers. In ERalpha- tumors,
      overexpression of epidermal growth factor receptor (EGFR) or c-erbB-2, leading to
      increased growth factor signaling, is observed such that mitogen-activated
      protein (MAP) kinase (MAPK) is significantly hyperactivated compared with
      ERalpha+ breast cancer. In ERalpha+/progesterone receptor-positive, estrogen
      dependent MCF-7 breast cancer cells, we stably overexpressed EGFR or
      constitutively active erbB-2, Raf, or MAP/extracellular signal-regulated kinase
      kinase, resulting in cell lines exhibiting hyperactivation of MAPK, estrogen
      independent growth, and the reversible down-regulation of ERalpha expression. By
      global mRNA profiling, we found a "MAPK signature" of approximately 400 genes
      consistently up-regulated or down-regulated in each of the MAPK+ cell lines. In
      several independent profile data sets of human breast tumors, the in vitro MAPK
      signature was able to accurately distinguish ER+ from ER- tumors. In addition,
      our in vitro mRNA profile data revealed distinct mRNA signatures specific to
      either erbB-2 or EGFR activation. A subset of breast tumor profiles was found to
      share extensive similarities with either the erbB-2-specific or the EGFR-specific
      signatures. Our results confirm that increased MAPK activation causes loss of
      ERalpha expression and suggest that hyperactivation of MAPK plays a role in the
      generation of the ERalpha- phenotype in breast cancer. These MAPK+ cell lines are
      excellent models for investigating the underlying mechanisms behind the ERalpha-
      phenotype.

PMID- 16585221
TI  - PGP9.5 methylation in diffuse-type gastric cancer.
AB  - Diffuse-type gastric cancer (DGC) is the most deadly form of gastric cancer and
      is frequently accompanied by peritoneal dissemination and metastasis. The
      specific molecular events involved in DGC pathogenesis remain elusive.
      Accumulating evidence of epigenetic inactivation in tumor suppressor genes led us
      to conduct a comprehensive screen to identify novel methylated genes in human
      cancers using pharmacologic unmasking and subsequent microarray analysis. We
      compared differential RNA expression profiles of DGC and intestinal-type gastric
      cancer (IGC) cell lines treated with 5-aza-2'-deoxycytidine using microarrays
      containing 22,284 genes. We identified 16 methylated genes, including many novel
      genes, in DGC cell lines and studied PGP9.5 with particular interest. In primary
      gastric cancers, PGP9.5 was found to be more frequently methylated in DGCs (78%)
      than in IGCs (36%; DGC versus IGC, P < 0.05). Furthermore, real-time methylation
      specific PCR analysis of PGP9.5 showed relatively higher methylation levels in
      DGC than in IGC. Our data thus implicate a molecular event common in the DGC
      phenotype compared with IGC.

PMID- 16585220
TI  - Gonadotropins activate proteolysis and increase invasion through protein kinase A
      and phosphatidylinositol 3-kinase pathways in human epithelial ovarian cancer
      cells.
AB  - Despite evidence that gonadotropins may facilitate peritoneal metastasis of
      ovarian cancer by increasing cell adhesion, the action and molecular mechanism of
      follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in ovarian cancer
      invasion is not well characterized. In the present study, we investigated the
      effects of FSH and LH on the invasive activity and the expression of metastasis
      related proteinases in human epithelial ovarian cancer by Western blot,
      zymography, reverse transcription-PCR (RT-PCR), ELISA, and Boyden chamber assay.
      Treatment with FSH or LH (10, 100, or 1,000 ng/mL) significantly increased the
      invasion of ovarian cancer cell lines, including BG-1, CaOV-3, and SKOV-3 cells
      but not OVCAR-3 cells. In addition, treatment of SKOV-3 cells with FSH or LH (100
      or 1,000 ng/mL) enhanced the expression and activation of matrix
      metalloproteinases (MMP-2 and MMP-9) as shown by RT-PCR, gelatin zymography, and
      ELISA. Pretreatment with [(2R)-2-(hydroxamido-carbonylmethyl)-4-methylpentanoyl]
      l-tryptophan methylamide (10 micromol/L), a total MMP inhibitor, and 3-(4
      phenoxyphenylsulfonyl)-propylthiirane (20 micromol/L), a specific gelatinase
      inhibitor, neutralized the proinvasive effect of gonadotropins in SKOV-3 cells.
      In addition, the secretion of tissue inhibitor of metalloproteinases (TIMP-1 and
      TIMP-2) and plasminogen activator inhibitor-1 was significantly decreased by FSH
      and LH (100 or 1,000 ng/mL). We further showed that gonadotropins induced an
      increase in SKOV-3 invasiveness via the activation of protein kinase A (PKA) and
      phosphatidylinositol 3-kinase (PI3K) signaling pathways. Taken together, these
      results suggest that gonadotropins may contribute to ovarian cancer metastasis
      via activation of proteolysis and increase in invasion through the PKA and PI3K
      pathways.

PMID- 16585222
TI  - Transcription analysis of human equilibrative nucleoside transporter-1 predicts
      survival in pancreas cancer patients treated with gemcitabine.
AB  - Gene expression analysis may help the management of cancer patients, allowing the
      selection of subjects responding to treatment. The aim of this study was the
      characterization of expression pattern of genes involved in gemcitabine activity
      in pancreas tumor specimens and its correlation with treatment outcome. The role
      of drug transport and metabolism on gemcitabine cytotoxicity was examined with
      specific inhibitors, whereas transcription analysis of human equilibrative
      nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK), 5'-nucleotidase (5'
      NT), cytidine deaminase (CDA), and ribonucleotide reductase subunits M1 and M2
      (RRM1 and RRM2) was done by quantitative reverse transcription-PCR in tumor
      tissue isolated by laser microdissection from surgical or biopsy samples of 102
      patients. Association between clinical outcome and gene expression levels was
      estimated using Kaplan-Meier method and Cox's proportional hazards model.
      Transport and metabolism had a key role on gemcitabine sensitivity in vitro;
      moreover, hENT1, dCK, 5'-NT, CDA, RRM1, and RRM2 were detectable in most tumor
      specimens. hENT1 expression was significantly correlated with clinical outcome.
      Patients with high levels of hENT1 had a significantly longer overall survival
      [median, 25.7; 95% confidence interval (95% CI), 17.6-33.7 months in the higher
      expression tertile versus median, 8.5; 95% CI, 7.0-9.9 months in the lower
      expression tertile]. Similar results were obtained with disease-free survival and
      time to disease progression, and the multivariate analysis confirmed the
      prognostic significance of hENT1. This study suggests that the expression levels
      of hENT1 may allow the stratification of patients based on their likelihood of
      survival, thus offering a potential new tool for treatment optimization.

PMID- 16585223
TI  - Early loss of Fhit in the respiratory tract of rodents exposed to environmental
      cigarette smoke.
AB  - The Fhit gene, encompassing the most active common human chromosomal fragile
      region, FRA3B, has been shown to act as a tumor suppressor. Several studies have
      shown significant Fhit alterations or Fhit protein loss in lung cancers from
      smokers compared with lung cancers from nonsmokers. To evaluate the role of Fhit
      under controlled experimental conditions, we exposed rodents to environmental
      cigarette smoke (ECS) and evaluated Fhit expression or Fhit protein in the
      respiratory tract. After 14 days of exposure to ECS, loss of Fhit protein in the
      bronchial/bronchiolar epithelium affected half of the tested B6-129(F(1)) mice,
      either wild type or Fhit(+/-). After 28 days, it affected the vast majority of
      the tested SKH-1 hairless mice and of A/J mice and all (UL53-3 x A/J)F(1) mice,
      either wild type or P53(+/-). In Sprague-Dawley rats, exposure to ECS for up to
      30 days caused a time-dependent loss of Fhit in pulmonary alveolar macrophages.
      Moreover, ECS down-regulated Fhit expression and significantly decreased Fhit
      protein in the rat bronchial epithelium. The oral administration of N
      acetylcysteine attenuated the ECS-related loss of Fhit, whereas oltipraz, 5,6
      benzoflavone, phenethyl isothiocyanate, and indole 3-carbinol, and their
      combinations had no significant effect. Parallel studies evaluated a variety of
      molecular, biochemical, and cytogenetic alterations in the respiratory tract of
      the same animals. In conclusion, there is unequivocal evidence that Fhit is an
      early, critical target in smoke-related lung carcinogenesis in rodents, and that
      certain chemopreventive agents can attenuate the occurrence of this gene
      alteration.

PMID- 16585225
TI  - It's Erren's brainchild, folks!

PMID- 16585224
TI  - Fruit and vegetable consumption and colorectal adenomas in the Nurses' Health
      Study.
AB  - Consumption of fruits and vegetables may confer protection from colorectal
      adenomas, but the limited observational and interventional evidence is
      inconclusive. We examined the association between fruit and vegetable consumption
      and the prevalence and incidence of adenomas of the distal colon and rectum in
      the Nurses' Health Study (NHS). We used data from 34,467 women in the NHS who had
      undergone colonoscopy or sigmoidoscopy during follow-up between 1980 and 1998.
      Consumption of fruits and vegetables was assessed in 1980, 1984, 1986, 1990, and
      1994 using a semiquantitative food frequency questionnaire; 1,720 prevalent cases
      of adenoma of the distal colon and rectum were diagnosed between 1980 and 1998.
      Frequent consumption of fruit was inversely related to the risk of being
      diagnosed with polyps, whereas little association was found for vegetable
      consumption. Women who reported consuming five or more servings of fruit a day
      had an odds ratio (OR) of 0.60 [95% confidence interval (95% CI), 0.44-0.81] for
      developing colorectal adenomas compared with women who consumed only one or fewer
      servings of fruit per day, after adjustment for relevant covariates (P(trend) =
      0.001). The respective OR for vegetable consumption was 0.82 (95% CI, 0.65-1.05;
      P(trend) = 0.1). Women who consumed four or more servings of legumes per week had
      a lower incidence of colorectal adenomas than women who reported consuming one
      serving per week or less (OR, 0.67; 95% CI, 0.51-0.90; P(trend) = 0.005).
      Frequent consumption of fruit may reduce the risk of colorectal adenomas.

PMID- 16585226
TI  - Sleep duration, melatonin, and breast cancer: compliment and complement.

PMID- 16585227
TI  - Genomic analysis of tumors by array comparative genomic hybridization: more is
      better.

PMID- 16585228
TI  - Will medical ethics be a casualty of the war on terror?

PMID- 16585229
TI  - Psychiatric evidence on the ultimate issue.
AB  - Federal Rule of Evidence 704(b) prevents psychiatrists and other expert witnesses
      in federal criminal trials from testifying as to whether a defendant did or did
      not have a mental state or condition comprising either an element of the crime or
      an element of the defense. This paper describes the origins of the Rule and its
      judicial development. The Rule is an exception to a 20th century trend that has
      seen witnesses increasingly permitted to address the ultimate issue. It has been
      applied inconsistently, has been criticized in appellate decisions, and has
      spawned an idiosyncratic legal definition of "helpful." Attempts to circumvent it
      have included inviting jurors to make inferences, inventing hypothetical cases
      that mimic the one before the court, and eliciting expert testimony on what is
      "possible" or "probable." Courts have held that rendering transparent the reasons
      behind an expert's conclusions can minimize the damage done by ultimate issue
      testimony.

PMID- 16585230
TI  - Commentary: Deceptions to the rule on ultimate issue testimony.
AB  - Federal Rule of Evidence 704(b) (and state counterparts) bars opinion testimony
      on the effect of mental state on an element of a crime or defense. The
      application of the rule involves substantial judicial discretion. As the
      jurisprudence to date indicates, deceptions to the rule circumvent its
      application.

PMID- 16585231
TI  - Pejorative testimony about opposing experts and colleagues: "fouling one's own
      nest".
AB  - Circumstances sometimes require expert witnesses under oath to express opinions
      about opposing experts or professional colleagues who work within their own
      professional, geographic, or organizational circle. This requirement poses some
      common problems that have not been well discussed in the literature. This article
      addresses some of those problems and suggests some useful solutions.

PMID- 16585232
TI  - Commentary: The medical practitioner as an expert.
AB  - This brief commentary reviews the concept of nest fouling, and advances the view
      that a different approach to giving expert testimony (that of impartially
      assisting the court) will largely negate nest-fouling issues.

PMID- 16585233
TI  - Clinicians' perceptions of boundaries in Brazil and the United States.
AB  - Although there has been considerable discussion of boundary excursions in
      clinician-patient relationships, little empirical research exists. This pilot
      study adds to the existing theoretical discussion by comparing perceptions by
      mental health professionals in Brazil and the United States of what may
      constitute boundary violations. Participants rated each possible boundary
      violation according to its degree of harm and professional unacceptability. Three
      distinct groupings of boundary violations were found: (1) core, consisting of the
      most serious violations; (2) separation of therapist and client lives, involving
      encounters between therapists and clients outside of therapy; and (3) disclosure
      and greeting behavior, involving disclosure of information about the therapist
      and greeting behavior. The U.S. and Brazilian perceptions were found to be
      surprisingly similar, with only a few differences.

PMID- 16585234
TI  - Psychiatric advance directives among public mental health consumers in five U.S.
      cities: prevalence, demand, and correlates.
AB  - Psychiatric advance directives (PADs) are legal instruments that allow competent
      persons to document their preferences regarding future mental health treatment
      and to designate a surrogate decisionmaker in the event they lose capacity to
      make reliable treatment decisions during an acute episode of psychiatric illness.
      This study reports the findings of a survey of 1,011 psychiatric outpatients in
      five U.S. cities about their interest in, and completion of, PADs. Across the
      sites, only 4 to 13 percent of participants had completed a PAD; however, between
      66 and 77 percent reported wanting to complete one if given assistance.
      Significantly higher demand for PADs was found among participants who were
      female; were nonwhite; had a history of self-harm, arrest, and decreased personal
      autonomy; and those who felt pressured to take medication. Actual completion of
      PADs was more likely among participants with higher insight, those reporting
      leverage by a representative payee, and those who felt external pressure to keep
      outpatient appointments for mental health treatment.

PMID- 16585235
TI  - Commentary: Psychiatric advance directives as tools for enhancing treatment of
      the mentally ill.
AB  - In this issue of the Journal, Swanson et al. explore the demand for and
      utilization of psychiatric advance directives (PADs), and discuss some of the
      barriers to their greater acceptance. This author suggests that PADs may be more
      widely accepted and utilized if they are viewed as tools for maximizing
      individual autonomy, with an emphasis on optimizing rather than merely
      restricting care.

PMID- 16585236
TI  - Sadistic personality disorder and comorbid mental illness in adolescent
      psychiatric inpatients.
AB  - Sadistic personality disorder (SPD) is a controversial diagnosis proposed in the
      DSM-III-R, but not included in the DSM-IV. Few studies have focused on this
      disorder in adolescents. This article describes the results of a study that
      sought to determine the presence of sadistic personality characteristics in
      psychiatrically hospitalized adolescents and of comorbid Axis I or personality
      disorder patterns in those youth with SPD or SPD traits. Fifty-six adolescents
      were assessed for sadistic and other personality disorders with the Structured
      Interview for DSM-III-R Personality Disorders-Revised (SIDP-R). Axis I disorders
      were assessed using the Diagnostic Interview for Children and Adolescents,
      Adolescent Version (DICA-R-A) and portions of the Schedule for Affective
      Disorders and Schizophrenia for School Age Children, Epidemiologic (K-SADS-E).
      The youth were divided into those with SPD and SPD traits, the Sadistic Group (n
      = 18), and the Nonsadistic Group (n = 38). A significant proportion of the
      adolescents in this study met full DSM criteria for SPD (14%). The Sadistic Group
      (32%) had significantly more Axis I and personality pathology than did the
      Nonsadistic Group. However, all but one in the Sadistic Group met criteria for
      other personality disorders, confounding the interpretation of these findings and
      consistent with adult literature studies. Subjects with sadistic personality
      characteristics were identified in this adolescent inpatient sample, and they had
      more extensive Axis I and II psychopathology than the comparison group. The
      validity of this disorder in younger populations requires further study. Future
      studies should also explore the impact that the mandatory use of the
      pleasure/gratification criterion has on the validity of the SPD diagnosis and
      whether the requisite presence of this criterion decreases the overlap currently
      noted between SPD and other Axis II diagnoses.

PMID- 16585237
TI  - Forensic psychiatric assessments of behaviorally disruptive physicians.
AB  - Forensic psychiatrists may be requested by a wide range of agencies and
      committees to assess physicians alleged to be behaviorally disruptive. Many of
      the adjudicatory procedures and questions of these agencies differ substantially
      from the familiar ones in civil litigation. Proximate cause and patient harm are
      not essential elements of the forensic questions raised by these health care
      agencies. In addition to assessing past professional conduct, the examiner is
      asked to opine about the examinee's present and future professional health and
      fitness for duty and what treatment or professional supervision, if any, may be
      needed to ensure the continuance of those professional capacities.

PMID- 16585238
TI  - A case control study: White-collar defendants compared with defendants charged
      with other nonviolent theft.
AB  - We examined the clinical, criminal, and sociodemographic characteristics of all
      white-collar crime defendants referred to the evaluation unit of a state center
      for forensic psychiatry. With 29,310 evaluations in a 12-year period, we found 70
      defendants charged with embezzlement, 3 with health care fraud, and no other
      white-collar defendants (based on the eight crimes widely accepted as white
      collar offenses). In a case-control study design, the 70 embezzlement cases were
      compared with 73 defendants charged with other forms of nonviolent theft. White
      collar defendants were found to have a higher likelihood of white race (adjusted
      odds ratio (adj. OR) = 4.51), more years of education (adj. OR = 3471), and a
      lower likelihood of substance abuse (adj. OR = .28) than control defendants.
      Logistic regression modeling showed that the variance in the relationship between
      unipolar depression and white-collar crime was more economically accounted for by
      education, race, and substance abuse.

PMID- 16585239
TI  - Persistent problems with the Munchausen syndrome by proxy label.
AB  - After nearly 30 years of clinical and legal experience, the definition of
      Munchausen syndrome by proxy remains controversial. As a result, mothers who
      present the problems of their children in ways perceived as unusual or
      problematic have become entangled in legal battles that should have been resolved
      clinically. Re-labeling the disorder as Pediatric Condition Falsification
      misdirects the focus onto mistakes and misunderstandings while avoiding the more
      crucial issue of intentions. Experts have enflamed the fears of harm by confusing
      warning signs with diagnostic signs and by citing retrospective studies instead
      of the more optimistic outcome studies. Accused mothers need the support of
      multidisciplinary teams but are often forced into contentious struggles with
      legal professionals and child protection services.

PMID- 16585240
TI  - Managing risk: systems approach versus personal responsibility for hospital
      incidents.
AB  - As hospitals grapple with the intense scrutiny of medical errors, administrators
      may find themselves in the midst of conflicting approaches to improving overall
      patient safety. One approach to addressing incidents that have been caused by
      individual practitioners is to consider weaknesses in the system of care at
      multiple levels that may have enabled an incident to occur. An alternative
      approach is to hold the individuals responsible for their performance errors and
      to impose penalties that have specific consequences for those individuals. These
      two approaches, though not mutually exclusive, can produce conflict among staff.

PMID- 16585241
TI  - Commentary: Medical errors, sentinel events, and malpractice.
AB  - Medical errors do not necessarily represent negligence. Even when a mental health
      professional deviates from the standard of care, minor injury to a patient is
      unlikely to result in a lawsuit. The standard of care is not the same as the
      quality of care. Quality of care refers to the total care a patient receives, the
      patient's health care decisions, and the available mental health services. As
      defined by the Joint Commission on Accreditation of Healthcare Organizations
      (JCAHO), "sentinel events," such as a patient's suicide, do not necessarily imply
      that a deviation in the standard of care occurred. Psychiatrists and hospital
      staff are held to an "ordinarily employed" standard of practice. The Institute of
      Medicine (IOM) guidelines recommend evidence-based care related to patient needs
      and values. Both JCAHO and IOM promote best practices. Experts err when they
      testify to a best practice standard in malpractice cases.

PMID- 16585242
TI  - Commentary: Systems, sensitivity, and "sorry".
AB  - This commentary first addresses the moral atmosphere necessary for a systems view
      of adverse outcomes and discusses the theory of accidents. Patients suffering
      adverse outcomes are described as needing acknowledgment, remorse, and remedy.
      Apologizing and informing patients or families about what actually happened are
      important risk management approaches.

PMID- 16585243
TI  - Individualizing justice after Atkins.
AB  - On August 6, 2005, newspapers and other media outlets reported that Daryl Atkins
      had been determined by a Virginia jury not to be retarded and therefore was
      mentally competent to receive the death penalty. A judge immediately scheduled
      his execution for December. Atkins, of course, is the convicted murderer whose
      case three years earlier had led the U.S. Supreme Court, in a landmark ruling, to
      declare that mentally retarded offenders are constitutionally exempt from the
      death penalty. While a bitter irony for Atkins, his family, and supporters, the
      Virginia jury's finding suggests that the practical effects of the Supreme
      Court's decision are less dramatic than many had anticipated. It shows that mere
      labels need not be determinative and that judges and juries as well as mental
      health experts called to assist them in capital cases can continue to work toward
      an individualized brand of justice.

PMID- 16585254
TI  - Cross-cultural psychiatry.

PMID- 16585255
TI  - The history of forensic psychiatry.

PMID- 16585256
TI  - Pathological lying.

PMID- 16585258
TI  - Asperger's disorder and murder.

PMID- 16585257
TI  - Patients with boundary issues.

PMID- 16585259
TI  - Theories of TL systems: failures, successes, conflicts, trends: insights into
      possible future materials and techniques.
AB  - In this paper some of the many theoretical models dealing with characteristics of
      TL materials are discussed. Special attention is given to some of the models
      dealing with the effects of ionisation density, that is Modified Track Structure
      Theory (MTST) and Microdosimetric Track Structure Theory (MTT) for the
      calculation of Heavy Charged Particle relative TL efficiencies, as well as solid
      state models based on conduction band/valence band theory. Failures, successes,
      conflicts and trends are highlighted as well as a peek into future avenues of
      research for dosimetric TL materials.

PMID- 16585260
TI  - Performance of CVD diamond as an optically and thermally stimulated luminescence
      dosemeter.
AB  - Diamond is a material with extreme physical properties. Its radiation hardness,
      chemical inertness and tissue equivalence qualify it as an ideal material for
      radiation dosimetry. In the present work, the optically stimulated luminescence
      (OSL) and thermoluminescence (TL) characteristics of a 10 microm thick CVD
      diamond (polycrystalline diamond films prepared by chemical vapor deposition)
      film were studied in order to test its performance as a beta radiation dosemeter.
      The TL response is composed of four main TL glow peaks; two of these are in the
      range of 150-200 degrees C and two additional peaks in the 250-400 degrees C
      temperature range. The integrated TL as a function of radiation dose is linear up
      to 100 Gy and increases with increasing dose exposure. The dose dependence of the
      integrated OSL exhibits a similar behavior. The observed OSL/TL behavior for the
      CVD diamond film clearly demonstrate its capability for applications in radiation
      dosimetry with special relevance in medical dosimetry owing to the diamond's
      intrinsic material properties.

PMID- 16585261
TI  - The use of alpha-Al2O3:C in Riso OSL single grains attachment system for
      assessing the spatial dose rate distribution due to incorporation of 90Sr in
      human teeth.
AB  - The possibility of using a single grain OSL attachment system developed by the
      Riso National Laboratory (Roskilde, Denmark) for assessing the spatial
      distribution of radionuclides incorporated in human tissues was investigated.
      Detectors containing arrays of single grains of alpha-Al2O3)C powder (Landauer
      Inc., USA) were prepared using aluminium discs (diameter 9.7 mm), which can
      accommodate 100 single grains in 0.3 mm holes positioned in a 10 x 10 grid. The
      luminescence and dosimetric properties of each grain were investigated by
      exposing the detectors to uniform photon radiation fields. After the
      characterisation of the detectors, the systems were tested to assess the spatial
      dose rate distribution because of 90Sr incorporated in a tooth sample extracted
      from an inhabitant of the Techa River region.

PMID- 16585262
TI  - Ionisation density dependence of the optically and thermally stimulated
      luminescence from Al2O3:C.
AB  - This paper presents an overview of recent results on ionisation density
      dependence of the thermally stimulated luminescence (TL) and optically stimulated
      luminescence (OSL) signals from Al2O3:C, with emphasis on the sensitivity,
      efficiency, shape of the TL/OSL curves and the emission spectrum. High-ionisation
      densities are created uniformly by accumulated high doses of low-linear energy
      transfer radiation (gamma, beta, X rays) or non-uniformly in heavy charged
      particle tracks, even at low fluences, as in the case of space radiation fields.
      Significant deep trap filling, which occurs at these high-ionisation densities,
      ultimately results in changes in the concentration of recombination centres (F+
      centres) and, consequently, in sensitivity changes and other effects. An OSL
      emission band at 335 nm has been observed in addition to the main F-centre
      luminescence band, and the relative intensities of these bands have been observed
      to be dependent on the ionisation density. The implications of these results and
      open issues are discussed.

PMID- 16585263
TI  - Optical excitation of LiF:Mg,Ti following alpha and beta irradiation.
AB  - It is demonstrated experimentally that optical excitation of irradiated LiF:Mg,Ti
      (TLD-100) by 4 eV photons has the same effect for both alpha particle (high
      ionisation density) irradiation and photon/electron irradiation. In both cases,
      peak 5a converts to peak 4 causing peak 4 to increase following the bleach. Such
      an observation is consistent with the major premise of track structure theory
      that radiation effects following heavy changed particle (HCP)/neutron irradiation
      are due exclusively to the interaction of the secondary electrons created by the
      HCP slowing down.

PMID- 16585264
TI  - Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory
      T cells that protect from IRBP-induced retinal autoimmunity.
AB  - Susceptibility to experimental autoimmune uveitis (EAU), a model for human
      uveitis induced in mice with the retinal antigen interphotoreceptor retinoid
      binding protein (IRBP), is controlled by "natural" CD4+CD25+ regulatory T (T reg)
      cells. To examine whether endogenous expression of IRBP is necessary to generate
      these T reg cells, we studied responses of IRBP knockout (KO) versus wild-type
      (WT) mice. Unexpectedly, not only WT but also IRBP KO mice immunized with a
      uveitogenic regimen of IRBP in complete Freund's adjuvant (CFA) exhibited CD25+
      regulatory cells that could be depleted by PC61 treatment, which suppressed
      development of uveitogenic effector T cells and decreased immunological responses
      to IRBP. These EAU-relevant T reg cells were not IRBP specific, as their activity
      was not present in IRBP KO mice immunized with IRBP in incomplete Freund's
      adjuvant (IFA), lacking mycobacteria (whereas the same mice exhibited normal T
      reg cell activity to retinal arrestin in IFA). We propose that mycobacterial
      components in CFA activate T reg cells of other specificities to inhibit
      generation of IRBP-specific effector T cells in a bystander fashion, indicating
      that effective T reg cells can be antigen nonspecific. Our data also provide the
      first evidence that generation of specific T reg cells to a native autoantigen in
      a mouse with a diverse T cell repertoire requires a cognate interaction.

PMID- 16585265
TI  - Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites
      of leukocyte extravasation in experimental autoimmune encephalomyelitis.
AB  - The endothelial cell monolayer of cerebral vessels and its basement membrane (BM)
      are ensheathed by the astrocyte endfeet, the leptomeningeal cells, and their
      associated parenchymal BM, all of which contribute to establishment of the blood
      brain barrier (BBB). As a consequence of this unique structure, leukocyte
      penetration of cerebral vessels is a multistep event. In mouse experimental
      autoimmune encephalomyelitis (EAE), a widely used central nervous system
      inflammatory model, leukocytes first penetrate the endothelial cell monolayer and
      underlying BM using integrin beta1-mediated processes, but mechanisms used to
      penetrate the second barrier defined by the parenchymal BM and glia limitans
      remain uninvestigated. We show here that macrophage-derived gelatinase (matrix
      metalloproteinase [MMP]-2 and MMP-9) activity is crucial for leukocyte
      penetration of the parenchymal BM. Dystroglycan, a transmembrane receptor that
      anchors astrocyte endfeet to the parenchymal BM via high affinity interactions
      with laminins 1 and 2, perlecan and agrin, is identified as a specific substrate
      of MMP-2 and MMP-9. Ablation of both MMP-2 and MMP-9 in double knockout mice
      confers resistance to EAE by inhibiting dystroglycan cleavage and preventing
      leukocyte infiltration. This is the first description of selective in situ
      proteolytic damage of a BBB-specific molecule at sites of leukocyte infiltration.

PMID- 16585266
TI  - Suppression of experimental autoimmune encephalomyelitis by extracellular
      adherence protein of Staphylococcus aureus.
AB  - Multiple sclerosis (MS) is a devastating inflammatory disorder of the central
      nervous system (CNS). A major hallmark of MS is the infiltration of T cells
      reactive against myelin components. T cell infiltration is mediated by the
      interaction of integrins of the beta1 and beta2 family expressed by lymphocytes
      with their endothelial counter-receptors, vascular cell adhesion molecule 1 and
      intercellular adhesion molecule (ICAM)-1, respectively. We have reported
      previously that extracellular adherence protein (Eap) of Staphylococcus aureus
      exerts antiinflammatory activities by interacting with ICAM-1 and blocking beta2
      integrin-dependent neutrophil recruitment. Here, we report that Eap inhibits
      experimental autoimmune encephalomyelitis (EAE) in mice. In vitro, Eap reduced
      adhesion of peripheral blood T cells to immobilized ICAM-1 as well as their
      adhesion and transmigration of TNF-activated human endothelium under static and
      shear flow conditions. These inhibitory effects were corroborated in two mouse
      models of inflammation. In a delayed-type hypersensitivity model, both T cell
      infiltration and the corresponding tissue edema were significantly reduced by
      Eap. In addition, Eap administration prevented the development of EAE and
      markedly decreased infiltration of inflammatory cells into the CNS. Strikingly,
      intervention with Eap after the onset of EAE suppressed the disease.
      Collectively, our findings indicate that Eap represents an attractive treatment
      for autoimmune neuroinflammatory disorders such as MS.

PMID- 16585267
TI  - Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that
      bind a Borrelia burgdorferi peptide.
AB  - An association has previously been shown between antibiotic-refractory Lyme
      arthritis, the human histocompatibility leukocyte antigen (HLA)-DR4 molecule, and
      T cell recognition of an epitope of Borrelia burgdorferi outer-surface protein A
      (OspA163-175). We studied the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes in 121
      patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis and
      correlated these frequencies with in vitro binding of the OspA163-175 peptide to
      14 DRB molecules. Among the 121 patients, the frequencies of HLA-DRB1-DQA1-DQB1
      haplotypes were similar to those in control subjects. However, when stratified by
      antibiotic response, the frequencies of DRB1 alleles in the 71 patients with
      antibiotic-refractory arthritis differed significantly from those in the 50
      antibiotic-responsive patients (log likelihood test, P = 0.006; exact test, P =
      0.008; effect size, Wn = 0.38). 7 of the 14 DRB molecules (DRB1*0401, 0101, 0404,
      0405, DRB5*0101, DRB1*0402, and 0102) showed strong to weak binding of OspA163
      175, whereas the other seven showed negligible or no binding of the peptide.
      Altogether, 79% of the antibiotic-refractory patients had at least one of the
      seven known OspA peptide-binding DR molecules compared with 46% of the antibiotic
      responsive patients (odds ratio = 4.4; P < 0.001). We conclude that binding of a
      single spirochetal peptide to certain DRB molecules is a marker for antibiotic
      refractory Lyme arthritis and might play a role in the pathogenesis of the
      disease.

PMID- 16585268
TI  - RGMa inhibition promotes axonal growth and recovery after spinal cord injury.
AB  - Repulsive guidance molecule (RGM) is a protein implicated in both axonal guidance
      and neural tube closure. We report RGMa as a potent inhibitor of axon
      regeneration in the adult central nervous system (CNS). RGMa inhibits mammalian
      CNS neurite outgrowth by a mechanism dependent on the activation of the RhoA-Rho
      kinase pathway. RGMa expression is observed in oligodendrocytes, myelinated
      fibers, and neurons of the adult rat spinal cord and is induced around the injury
      site after spinal cord injury. We developed an antibody to RGMa that efficiently
      blocks the effect of RGMa in vitro. Intrathecal administration of the antibody to
      rats with thoracic spinal cord hemisection results in significant axonal growth
      of the corticospinal tract and improves functional recovery. Thus, RGMa plays an
      important role in limiting axonal regeneration after CNS injury and the RGMa
      antibody offers a possible therapeutic agent in clinical conditions characterized
      by a failure of CNS regeneration.

PMID- 16585269
TI  - Retention of function without normal disc morphogenesis occurs in cone but not
      rod photoreceptors.
AB  - It is commonly assumed that photoreceptor (PR) outer segment (OS) morphogenesis
      is reliant upon the presence of peripherin/rds, hereafter termed Rds. In this
      study, we demonstrate a differential requirement of Rds during rod and cone OS
      morphogenesis. In the absence of this PR-specific protein, rods do not form OSs
      and enter apoptosis, whereas cone PRs develop atypical OSs and are viable. Such
      OSs consist of dysmorphic membranous structures devoid of lamellae. These tubular
      OSs lack any stacked lamellae and have reduced phototransduction efficiency. The
      loss of Rds only appears to affect the shape of the OS, as the inner segment and
      connecting cilium remain intact. Furthermore, these structures fail to associate
      with the specialized extracellular matrix that surrounds cones, suggesting that
      Rds itself or normal OS formation is required for this interaction. This study
      provides novel insight into the distinct role of Rds in the OS development of
      rods and cones.

PMID- 16585270
TI  - The human Mis12 complex is required for kinetochore assembly and proper
      chromosome segregation.
AB  - During cell division, kinetochores form the primary chromosomal attachment sites
      for spindle microtubules. We previously identified a network of 10 interacting
      kinetochore proteins conserved between Caenorhabditis elegans and humans. In this
      study, we investigate three proteins in the human network (hDsn1Q9H410,
      hNnf1PMF1, and hNsl1DC31). Using coexpression in bacteria and fractionation of
      mitotic extracts, we demonstrate that these proteins form a stable complex with
      the conserved kinetochore component hMis12. Human or chicken cells depleted of
      Mis12 complex subunits are delayed in mitosis with misaligned chromosomes and
      defects in chromosome biorientation. Aligned chromosomes exhibited reduced
      centromere stretch and diminished kinetochore microtubule bundles. Consistent
      with this, localization of the outer plate constituent Ndc80HEC1 was severely
      reduced. The checkpoint protein BubR1, the fibrous corona component centromere
      protein (CENP) E, and the inner kinetochore proteins CENP-A and CENP-H also
      failed to accumulate to wild-type levels in depleted cells. These results
      indicate that a four-subunit Mis12 complex plays an essential role in chromosome
      segregation in vertebrates and contributes to mitotic kinetochore assembly.

PMID- 16585271
TI  - Nonvesicular sterol movement from plasma membrane to ER requires oxysterol
      binding protein-related proteins and phosphoinositides.
AB  - Sterols are moved between cellular membranes by nonvesicular pathways whose
      functions are poorly understood. In yeast, one such pathway transfers sterols
      from the plasma membrane (PM) to the endoplasmic reticulum (ER). We show that
      this transport requires oxysterol-binding protein (OSBP)-related proteins (ORPs),
      which are a large family of conserved lipid-binding proteins. We demonstrate that
      a representative member of this family, Osh4p/Kes1p, specifically facilitates the
      nonvesicular transfer of cholesterol and ergosterol between membranes in vitro.
      In addition, Osh4p transfers sterols more rapidly between membranes containing
      phosphoinositides (PIPs), suggesting that PIPs regulate sterol transport by ORPs.
      We confirmed this by showing that PM to ER sterol transport slows dramatically in
      mutants with conditional defects in PIP biosynthesis. Our findings argue that
      ORPs move sterols among cellular compartments and that sterol transport and
      intracellular distribution are regulated by PIPs.

PMID- 16585272
TI  - A specialized processing body that is temporally and asymmetrically regulated
      during the cell cycle in Saccharomyces cerevisiae.
AB  - RNase mitochondrial RNA processing (MRP) is an essential ribonucleoprotein
      endoribonuclease that functions in the degradation of specific mRNAs involved in
      cell cycle regulation. We have investigated where this processing event occurs
      and how it is regulated. As expected, results demonstrate that RNase MRP is
      predominantly localized in the nucleolus, where it processes ribosomal RNAs.
      However, after the initiation of mitosis, RNase MRP localizes throughout the
      entire nucleus and in a single discrete cytoplasmic spot that persists until the
      completion of telophase. Furthermore, this spot was asymmetrically found in
      daughter cells, where the RNase MRP substrate, CLB2 mRNA, localizes. Both the
      mitotic exit network and fourteen early anaphase release pathways are
      nonessential but important for the temporal changes in localization. Asymmetric
      localization was found to be dependent on the locasome. The evidence suggests
      that these spots are specialized processing bodies for the degradation of
      transcripts that are cell cycle regulated and daughter cell localized. We have
      called these TAM bodies for temporal asymmetric MRP bodies.

PMID- 16585274
TI  - Cri du chat syndrome and congenital heart disease: a review of previously
      reported cases and presentation of an additional 21 cases from the Pediatric
      Cardiac Care Consortium.
AB  - OBJECTIVES: To analyze the cases submitted to the Pediatric Cardiac Care
      Consortium (PCCC) database from 1982 to 2002 to determine the frequency and
      distribution of congenital heart disease (CHD) found in this population, to
      review the literature for previously published accounts of CHD in this
      population, and to review current genotype-phenotype associations for cri du chat
      (CDC) syndrome with CHD. METHODS: We performed a retrospective review of the
      98422 CHD cases submitted to the PCCC between 1982 and 2002, to find patients who
      had a noncardiac diagnosis of CDC syndrome. RESULTS: A total of 21 patients (15
      female and 6 male patients) were identified. Although some patients had multiple
      cardiac anomalies, they were categorized according to primary diagnoses on the
      basis of the most hemodynamically significant component. The patient groups were
      ventricular septal defect (n = 6), patent ductus arteriosus (n = 6), tetralogy of
      Fallot (n = 5), pulmonary valve atresia with ventricular septal defect (n = 2),
      pulmonary valve stenosis (n = 1), and double-outlet right ventricle (n = 1).
      Eighteen of the 21 patients underwent surgical repair of their defects. There was
      1 late operative death. To determine whether the observed frequency of these
      cardiac defects among patients with CDC syndrome was comparable to that of the
      general population of patients with CHD, data for all cases submitted to the PCCC
      from 1982 to 2002 were used. Use of these numbers to determine expected
      frequencies for these defects showed significantly greater proportions of
      patients with these specific lesions among the patients with CDC syndrome.
      CONCLUSIONS: Currently there is no clear understanding of the genomic cause of
      the prevalence of these defects in the population with CDC syndrome, although CHD
      has been noted among patients with other deletion syndromes.

PMID- 16585273
TI  - Mcp5, a meiotic cell cortex protein, is required for nuclear movement mediated by
      dynein and microtubules in fission yeast.
AB  - During meiotic prophase I of the fission yeast Schizosaccharomyces pombe,
      oscillatory nuclear movement occurs. This promotes homologous chromosome pairing
      and recombination and involves cortical dynein, which plays a pivotal role by
      generating a pulling force with the help of an unknown dynein anchor. We show
      that Mcp5, the homologue of the budding yeast dynein anchor Num1, may be this
      putative dynein anchor. mcp5+ is predominantly expressed during meiotic prophase,
      and GFP-Mcp5 localizes at the cell cortex. Moreover, the mcp5Delta strain lacks
      the oscillatory nuclear movement. Accordingly, homologous pairing and
      recombination rates of the mcp5Delta strain are significantly reduced.
      Furthermore, the cortical localization of dynein heavy chain 1 appears to be
      reduced in mcp5Delta cells. Finally, the full function of Mcp5 requires its
      coiled-coil and pleckstrin homology (PH) domains. Our results suggest that Mcp5
      localizes at the cell cortex through its PH domain and functions as a dynein
      anchor, thereby facilitating nuclear oscillation.

PMID- 16585275
TI  - Decade of experience with vascular rings at a single institution.
AB  - OBJECTIVE: Over the past decade, the diagnostic workup of vascular rings has
      changed at our institution. Despite surgical intervention, we have observed long
      term aerodigestive issues in some patients. In an effort to better characterize
      these pre- and postoperative issues, we reviewed a decade of experience at our
      institution. METHODS: We performed a complete chart review of all patients
      identified as having surgical intervention for vascular ring between January 1993
      and December 2003. A questionnaire was mailed to the family of each patient to
      ascertain a subjective assessment of long-term postoperative issues. RESULTS:
      Thirty-eight patients were reviewed and categorized as to specific arch anomaly.
      Associated cardiac anomalies were present in 29% of patients. Chronic feeding
      difficulties persisted in 18% of patients, and airway issues remained in nearly
      half of the patients. Patients with underlying genetic syndromes had less
      resolution of symptoms compared with nonsyndromic children. Chronic respiratory
      symptoms were present in 80% of patients operated <6 months, 15% if operated
      between 6 months and 3 years, and 42% of patients operated after 3 years of age.
      CONCLUSIONS: Aerodigestive issues may persist after vascular ring division
      despite initial improvement. Accurate preoperative anatomic imaging is imperative
      to surgical planning.

PMID- 16585276
TI  - Urine interleukin-8 as a marker of vesicoureteral reflux in infants.
AB  - OBJECTIVE: Vesicoureteral reflux (VUR) is a common finding in children presenting
      with urinary tract infection (UTI) and prenatally diagnosed urinary tract
      dilatation and in relatives of index patients. Children with VUR are at risk for
      ongoing renal damage with subsequent infections. Detecting VUR and renal scarring
      currently depends on imaging modalities with associated problems of radiation,
      invasiveness, and expense. Noninvasive methods would greatly facilitate diagnosis
      and would also help in identifying relatives of index cases who should be
      screened. Interleukin-8 (IL-8) is produced by epithelial cells of the renal tract
      in response to inflammatory stimuli and has been shown to increase during acute
      UTI. The objective of this study was to assess the urine levels of IL-8 as a
      noninvasive marker of VUR in infants in the absence of a recent UTI episode.
      METHODS: We evaluated urine concentrations of IL-8 in 59 infants aged 1 month to
      2 years. All infants were free of UTI for a minimum of 3 weeks before IL-8
      evaluation. Infants were divided into 3 groups: group A, subjects with proven VUR
      (24 infants aged 0.15-1.95 years, median 0.43); group B, subjects with a history
      of UTI but negative investigation for VUR (14 infants aged 0.32-1.95 years,
      median 0.57); and group C, subjects without any history of acute or chronic
      condition that might impair renal function (21 infants aged 0.08-1.92 years,
      median 0.33). IL-8 concentrations were determined by a commercially available
      quantitative enzyme-linked immunosorbent assay. To avoid dilution effects,
      urinary levels of IL-8 were expressed as the ratio of cytokine-to-urinary
      creatinine. RESULTS: Results were presented as medians and ranges. The Kruskal
      Wallis test, the Mann-Whitney rank sum U test, and the Spearman rank order
      correlation test were performed for the univariate analysis. Two-tailed P values
      were calculated and the conventional level of significance P < .05 was applied in
      all cases. Infants in groups A and B had been free of UTI for a period of 3 to 52
      weeks (median, 5.0 weeks) and 3 to 78 weeks (median, 4.5 weeks), respectively,
      before IL-8 determination. No significant difference was noted in the length of
      the UTI-free period between groups A and B (P = .469). Urine creatinine
      concentrations did not differ among groups A, B, and C (medians 1.15, 2.25, and
      1.15 micromol/mL, respectively; P = .080). The median urine IL-8/creatinine
      concentrations (pg/micromol) were 40.5 (range, 2.04-3874) in group A, 1.91
      (range, 0.001-386) in group B, and 2.47 (range, 0.002-55.6) in group C. Urine IL
      8/creatinine concentrations were significantly higher in group A than both in
      group B (P = .0003) and in group C (P < .0001). No significant difference was
      observed between groups B and C (P = .749). In group A, no significant
      correlation was shown between IL-8/creatinine concentrations and the presence of
      renal parenchymal damage (P = .506), reflux grade (P = .770), or time from UTI (P
      = .155). A receiver-operator characteristic curve was constructed by plotting the
      sensitivity versus the specificity for different cutoff concentrations of IL
      8/creatinine. With a cutoff concentration of urinary IL-8/creatinine at 5
      pg/micromol, the sensitivity of this marker in diagnosing VUR was 88%, the
      specificity 69%, the positive prognostic value 66%, and the negative prognostic
      value 89%. In higher cutoff concentrations, specificity of the marker increased
      but sensitivity rapidly decreased. CONCLUSIONS: We present evidence that urine IL
      8 concentrations remain elevated in infants with VUR even in the absence of UTI
      and that a cutoff of 5 pg/micromol IL-8/creatinine is of high sensitivity and
      adequate specificity for diagnosing VUR. Elevated urine IL-8 levels in VUR and
      renal scarring have already been reported; however, the present study is, to our
      knowledge, the first to confirm significant differences between infants with VUR
      and infants with a history of UTI alone and healthy controls, and to suggest a
      reliable cutoff concentration for diagnosing VUR. Our findings additionally
      suggest that inflammatory process in VUR is ongoing even after UTI has resolved,
      pointing against the currently held belief that sterile reflux cannot harm
      kidneys. The chronic inflammatory cell infiltrate associated with reflux
      nephropathy rather than VUR itself might offer an explanation for the secretion
      of IL-8, which may well be independent of reflux grade. Using urine IL-8 for
      diagnosing VUR is not free of limitations, because IL-8 may be elevated as a
      result of urinary tract manipulation or undetected UTI. In addition, this study
      focused on infants and not in older children with longstanding VUR. Increased
      urine IL-8 concentrations after UTI has resolved is a promising noninvasive
      marker for an initial screening for VUR in infancy with high sensitivity and
      adequate specificity.

PMID- 16585277
TI  - Who receives a diagnosis of attention-deficit/ hyperactivity disorder in the
      United States elementary school population?
AB  - OBJECTIVE: To investigate factors that are associated with the probability of
      attention-deficit/hyperactivity disorder (ADHD) diagnosis among U.S. elementary
      school children, including child, family, school, and policy factors. METHODS:
      Logistic regression was used to estimate relative risks associated with
      independent variables using a nationally representative sample of 9278 children
      in the 2002 follow-up of the Early Childhood Longitudinal Survey-Kindergarten
      Cohort. Most children in the sample were in third grade at this point. Previous
      ADHD diagnoses by professionals were reported by parent respondents. RESULTS: A
      total of 5.44% of children were reported to have received an ADHD diagnosis.
      Girls, black children, and Hispanic children were less likely to have the
      diagnosis even after controlling for other characteristics. Living with one's
      biological father was negatively associated with ADHD diagnosis. We also found
      regional variation in diagnosis with the western region of the United States
      having significantly lower instances of ADHD cases. Higher diagnosis rates were
      associated with having an older teacher, and lower rates were associated with
      having a white teacher, relative to a nonwhite teacher. In schools that were
      subject to stricter state-level performance accountability laws, we found higher
      odds of ADHD diagnoses, but we found no differences associated with larger class
      sizes or the presence of state laws that restrict school personnel from
      discussing ADHD treatment options with parents. CONCLUSIONS: ADHD diagnosis is
      likely to be influenced by a child's social and school environment as well as
      exogenous child characteristics. Concerns that increased pressures for school
      performance are associated with increased ADHD diagnoses may be justified.

PMID- 16585278
TI  - Severe pediatric influenza in California, 2003-2005: implications for
      immunization recommendations.
AB  - OBJECTIVE: The 2003-2004 influenza season was marked by both the emergence of a
      new drift "Fujian" strain of influenza A virus and prominent reports of increased
      influenza-related deaths in children in the absence of baseline data for
      comparison. In December 2003, the California Department of Health Services
      initiated surveillance of children who were hospitalized in California with
      severe influenza in an attempt to measure its impact and to identify additional
      preventive measures. METHODS: From December 2003 to May 2005, surveillance of
      children who were hospitalized in PICUs or dying in the hospital with laboratory
      evidence of influenza was performed by hospital infection control practitioners
      and local public health departments using a standardized case definition and
      reporting form. RESULTS: In the 2003-2004 and 2004-2005 influenza seasons, 125
      and 35 cases, respectively, of severe influenza in children were identified in
      California. The mean and median age of cases were 3.1 years and 1.5 years, with
      breakdown as follows: < 6 months, 39 (24%); 6 to 23 months, 53 (33%); 2 to 4
      years, 40 (25%); 5 to 11 years, 15 (9%); and 12 to 17 years, 13 (8%). Fifty-three
      percent (85 of 160) had an underlying medical condition(s), including a
      neurologic disorder (n = 36), chronic pulmonary disease (n = 26), genetic
      disorder (n = 19), cardiac disease (n = 18), prematurity (n = 14),
      immunocompromised status (n = 12), endocrine/renal disease (n = 2), and other (n
      = 1). Only 16% (15 of 96) of all patients had received influenza vaccination.
      Thirty-seven patients had an underlying illness that met existing Advisory
      Committee on Immunization Practices (ACIP) or American Academy of Pediatrics
      (AAP) recommendations for immunization, but only 8 had been vaccinated.
      CONCLUSIONS: More than 3 times as many children were reported to be hospitalized
      in intensive care with influenza in California during the 2003-2004 season
      compared with the 2004-2005 season. Because children who are younger than 6
      months remain at highest risk for severe influenza yet cannot currently be
      immunized, development and validation of preventive measures for them (eg,
      maternal immunization, breastfeeding, immunization of young infants and their
      close contacts) are urgently needed. ACIP's recent recommendation for influenza
      vaccination of children with conditions that can compromise respiratory function
      (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, other
      neuromuscular disorders) is further supported by the frequency of underlying
      neurologic disease in these cases of severe influenza. A significant proportion
      of children with severe influenza in California, including children who are aged
      2 to 4 years or have underlying genetic syndromes or prematurity, would not have
      been routinely recommended for influenza vaccination in 2005-2006 ACIP and AAP
      recommendations, calling into question whether such guidelines should be
      expanded. Continued surveillance for severe influenza-related morbidity and
      mortality is important to measure the impact of influenza on children.

PMID- 16585279
TI  - Universal newborn hearing screening and postnatal hearing loss.
AB  - OBJECTIVE: The goal of this study was to determine the percentage of children who
      have a postnatal permanent childhood hearing impairment (PCHI) and the percentage
      thereof who have risk indicators for a postnatal hearing loss. METHODS: Data were
      drawn retrospectively from the clinical charts of children who had bilateral PCHI
      (>40 dB hearing level, better ear, unaided) and had undergone universal newborn
      hearing screening (UNHS) between 1995 and 2000 in various Austrian hospitals. A
      hearing loss was recognized as postnatal when a child passed UNHS but was later
      found to have a hearing impairment. The presence of risk indicators, as suggested
      by the Year 2000 Statement of the American Joint Committee on Infant Hearing
      (JCIH), was assessed by reviewing the children's clinical charts. RESULTS: Of a
      total of 105 children with bilateral PCHI, 23 (22%) showed postnatal impairment.
      After correction of this number for underascertainment, postnatal impairment was
      estimated to account for 25% of all bilateral PCHI at age 9 years. Risk
      indicators were found in 17 children but did not fully correspond to those
      proposed by the JCIH. The risk factors found were a family history of hearing
      loss (3 children), meningitis (2), craniofacial malformation (2), persistent
      pulmonary hypertension (1), congenital cytomegaly infection (1), extracorporeal
      membrane oxygenation (1), recurrent otitis media with effusion (1), and, in
      addition to the JCIH list, ototoxic therapy (5), and birth before 33rd
      gestational week (2) (1 child had a combination of the last 2). Six children
      showed no risk indicators for the postnatal hearing loss. CONCLUSIONS: Our
      findings suggest that approximately 25% of bilateral childhood hearing loss is
      postnatal, which supports the leading role of UNHS in detecting PCHI. Provisions
      for also identifying postnatal cases nevertheless are justified. Because in some
      of these children no risk indicators are detectable and in others the hearing
      deterioration starts after age 3 years, audiologic monitoring of at-risk children
      up to this age may not be sufficient. Additional methods, such as hearing
      screening at nursery schools or schools, are recommended.

PMID- 16585280
TI  - Fathers and the well-child visit.
AB  - OBJECTIVE: Societal and economic shifts have expanded the roles that fathers play
      in their families. Father involvement is associated with positive cognitive,
      developmental, and sociobehavioral child outcomes such as improved weight gain in
      preterm infants, improved breastfeeding rates, higher receptive language skills,
      and higher academic achievement. However, father involvement in health care has
      been studied little, especially among nonmarried, minority fathers. Fathers are a
      significant part of the child's medical home, and comprehensive involvement of
      both parents is ideal for the child's well-being and health. Well-child visits
      (WCVs) represent opportunities for fathers to increase their involvement in their
      child's health care while learning valuable information about the health and
      development of their child. The objective of this study was to explore fathers'
      involvement in, experience and satisfaction with, and barriers to WCVs using
      qualitative methods. METHODS: In-depth, semistructured, qualitative interviews
      were conducted in 2 cities with a subsample of fathers who were participating in
      the national Fragile Families and Child Wellbeing Study. The 32 fathers who
      participated in our study come from a nested qualitative study called Time, Love,
      and Cash in Couples with Children. Fathers in our study reside in Chicago or
      Milwaukee and were interviewed about health care issues for 1.5 hours when the
      focal child was 3 years of age. Questions focused on the father's overall
      involvement in his child's health care, the father's attendance and experiences
      at the doctor, health care decision-making between mother and father, assessment
      of focal child's health, gender/normative roles, and the father's health. The
      open-ended questions were designed to allow detailed accounts and personal
      stories as told by the fathers. Coding and analysis were done using content
      analysis to identify themes. Particular themes that were used for this study
      focused on ideals of father involvement and dis/satisfaction, barriers to, and
      experiences in the health care system. RESULTS: Of the 50 fathers from the Time,
      Love, and Cash in Couples with Children study in the 2 cities, 3 had moved out of
      the state, 6 were in jail, 7 had been lost in earlier follow-up, and 1 had died,
      leaving 33 eligible respondents. Of those, 1 refused to participate, resulting in
      a final sample of 32 fathers and an adjusted response rate of 97%. The mean age
      was 31 years, and the sample was 56% black, 28% Hispanic, and 15% white; 53% were
      nonmarried. Only 2 fathers had attained a college degree or higher, and 84% of
      the fathers were employed at the time of the interview. The majority (53%) had
      attended a WCV and 84% had been to see a doctor with their child in the past
      year. Reasons for attending a WCV included (1) to gather information about their
      child, (2) to support their child, (3) to ask questions and express concerns, and
      (4) to gain firsthand experience of the doctor and the WCV. Fathers reported
      positive and negative experiences in their encounters with the health care
      system. The 3 main contributors to fathers' satisfaction with health care
      professionals were (1) inclusive interactions with the physician, (2) the
      perception of receiving quality care, and (3) receiving clear explanations. The
      negative experiences were often specific instances and noted along with positive
      comments. The negative experiences that were mentioned by the fathers included
      feeling viewed suspiciously by health care staff, being perceived as having a
      lesser emotional bond with their child than the mother, and the perception that
      they were receiving a lower quality of service compared with the mother. Major
      barriers to attending WCVs include employment schedules as well as their
      relationship with the focal child's mother. For example, some fathers stated that
      they did not attend WCVs because that was a responsibility that the mother
      assumed within the family. Other fathers lacked confidence in their parenting
      skills, which resulted in lower involvement levels. Also mentioned were health
      care system barriers such as inconvenient office hours and a lack of access to
      their child's records. Despite the presence of several barriers that seem to
      prevent fathers from attending WCVs, many fathers (20 of 32;63%) mentioned
      "situational flexibility," which enables them to overcome the stated barriers and
      attend doctor visits. For example, some fathers viewed the seriousness of the
      visit such as "ear surgery" as a reason to rearrange their schedules and attend a
      doctor visit with their child. CONCLUSION: The majority of fathers from our
      sample have attended a WCV, and most have been to their child's doctor in the
      past year; WCVs and doctor appointments are ways in which fathers are involved in
      their child's health care. Fathers detailed specific reasons for why they attend
      WCVs, such as to support their child, ask questions, express concerns, and gather
      information firsthand. The fathers reported more positive than negative
      experiences with the health care staff, and, overall, they are satisfied with
      their experiences with the health care system. Reasons for satisfaction include
      feeling as though their questions had been dealt with seriously and answered
      appropriately. However, the fathers in our study did report a variety of barriers
      to health care involvement, including conflicting work schedules, a lack of
      confidence in their parental role, and health care system barriers. Professionals
      who care for children and families need to explore creative ways to engage
      fathers in the structured health care of their children. For example,
      pediatricians can stress the benefits of both parents being involved in their
      child's health care while reframing the importance of WCVs. Understanding that
      many fathers have situational flexibility when it comes to health care encounters
      may encourage physicians to suggest more actively that fathers attend WCVs.
      Pediatricians can also support existing public policies such as the national 2003
      Responsible Fatherhood Act that provides grants and programs that promote the
      father's role in the family and advocate for additional policies that would
      foster quality father involvement. Continued collaboration among families,
      physicians, and other health care professionals is essential to support father
      involvement and ensure positive health outcomes for children.

PMID- 16585281
TI  - Predictors of breastfeeding duration: evidence from a cohort study.
AB  - OBJECTIVE: To report the duration of breastfeeding among a population of
      Australian women and to identify factors that are associated with the duration of
      full breastfeeding to 6 months and any breastfeeding to 12 months. METHODS:
      Participants were 587 women who were recruited from 2 maternity hospitals in
      Perth and completed a baseline questionnaire just before or shortly after
      discharge from the hospital. Women were followed up by telephone interview at 4,
      10, 16, 22, 32, 40, and 52 weeks postpartum. Data collected included
      sociodemographic, biomedical, hospital-related, and psychosocial factors
      associated with the initiation and the duration of breastfeeding. Cox's
      proportional hazards model was used to identify factors that were associated with
      the risk for discontinuing full breastfeeding before 6 months and any
      breastfeeding before 12 months. RESULTS: At 6 months of age, fewer than one half
      of infants were receiving any breast milk (45.9%), and only 12% were being fully
      breastfed. By 12 months, only 19.2% of infants were still receiving any breast
      milk. Breastfeeding duration was independently, positively associated with
      maternal infant feeding attitudes and negatively associated with breastfeeding
      difficulties in the first 4 weeks, maternal smoking, introduction of a pacifier,
      and early return to work. CONCLUSIONS: Relatively few women achieved the
      international recommendations for duration of full and overall breastfeeding.
      Women should receive anticipatory guidance while still in the hospital on how to
      prevent or manage common breastfeeding difficulties and should be discouraged
      from introducing a pacifier before 10 weeks, if at all. Improved maternity leave
      provisions and more flexible working conditions may help women to remain at home
      with their infants longer and/or to combine successfully breastfeeding with
      employment outside the home.

PMID- 16585282
TI  - Sun protection practices among offspring of women with personal or family history
      of skin cancer.
AB  - OBJECTIVE: Family history of skin cancer is an important determinant of skin
      cancer risk for offspring. No previous study of the effect of personal or family
      history of skin cancer on the sun protection behaviors of the offspring has been
      published. METHODS: A retrospective study was conducted of the sun protection
      behaviors of the adolescent participants in the Growing Up Today Study (GUTS),
      who were offspring of mothers from the Nurses Health Study II. Adolescents'
      surveys were matched with their mothers' reports of a personal or family history
      of skin cancer and compared with adolescents whose mothers did not report a
      personal or family history of skin cancer. The outcome measures were (1)
      occurrence of frequent sunburns during the past summer, (2) use of a tanning bed
      during the past year, and (3) routine use of sunscreen. Frequent sunburns were
      defined as the report of > or = 3 sunburns during the past summer. We compared
      those who reported having used a tanning bed in the past year at least once with
      those who reported no tanning bed use in the past year. Routine use of sunscreen
      was defined as a respondent who replied that he or she "always" or "often" used
      sunscreen with sun protection factor of 15 or more when he or she was outside for
      > 15 minutes on a sunny day during the past summer. General estimating equations
      were used to calculate odds ratios and 95% confidence intervals adjusted for
      gender, age, color of untanned skin, and number of friends who were tanned. We
      also conducted an additional analysis restricted to children whose mothers had
      received a diagnosis of skin cancer in which we assessed sun protection behaviors
      according to the child's age and mother's age at the time of the mother's
      diagnosis and the number of years that had passed since the diagnosis of the
      mother's skin cancer. RESULTS: In 1999, 9943 children reported their sun
      protection behaviors; 8697 of their mothers had not received a diagnosis of skin
      cancer or reported a family history of melanoma, 463 participants' mothers had
      received a diagnosis of skin cancer, and 783 participants' mothers reported a
      family history of melanoma. Between 1989 and 1999, 371 mothers of GUTS
      participants received a diagnosis of skin cancer: melanoma (n = 44), squamous
      cell (n = 39), and basal cell cancer (n = 311); 23 mothers received a diagnosis
      of > 1 type of skin cancer. Because GUTS includes siblings from the same family,
      the 371 mothers with skin cancer had 463 offspring in GUTS. Offspring of mothers
      with skin cancer were slightly more likely to report frequent sunburns in the
      past year compared with those with neither maternal diagnosis nor family history
      (39% vs 36%). Tanning bed use was not significantly different among those with
      either a maternal diagnosis of skin cancer or family history of melanoma as
      compared with nonaffected adolescents (8% vs 9% vs 10%). Sunscreen use among
      offspring of mothers with skin cancer was higher than among those whose mothers
      had a family history of melanoma or mothers with no personal history of skin
      cancer (42% vs 33% vs 34%). Tan-promoting attitudes were also similar across all
      groups. Only 25% thought that a natural skin color was most attractive, and on
      average, 25% in each group agreed that it was worth burning to get a tan.
      Children of mothers who had received a diagnosis > 2 years in the past were less
      likely to use sunscreen, more likely to sunburn, and more likely to use tanning
      beds than children of mothers with a more recent diagnosis, although the results
      did not reach statistical significance. CONCLUSION: Frequent sunburns, suboptimal
      sunscreen use, and high rates of tanning bed use are commonplace even among the
      children of health professionals who are at risk for developing skin cancer
      themselves as a result of personal or family history. With new information on
      family risk, pediatricians can use the potential of a teachable moment to ensure
      optimal sun protection for children who are at risk.

PMID- 16585283
TI  - A national survey of the acceptability of quitlines to help parents quit smoking.
AB  - OBJECTIVE: Provision of telephone smoking cessation counseling can increase the
      rate of quitting smoking. The US Public Health Service recently helped to
      establish a free national quitline enrollment service. No previous surveys have
      assessed the acceptability to parents of enrollment in quitline counseling in the
      context of their child's health care visits. Therefore, the objective of this
      study was to assess acceptability to parents of enrollment in quitline counseling
      and to compare that with the reported rate of actually being enrolled in any
      smoking cessation counseling outside the office in the context of the child's
      health care visit. METHODS: Data were collected by a national random-digit-dial
      telephone survey of households from September to November 2004. The sample is
      weighted by race and gender on the basis of the current US Census to be
      representative of the US population. RESULTS: Of 3615 eligible respondents
      contacted, 3011 (83.3%) completed surveys; 958 (31.8%) who completed the survey
      were parents with children under the age of 18 years. Of these parents, 187
      (19.7%) were self-identified smokers. Of the parents who smoked, 113 (64.2%) said
      that they would accept enrollment in a telephone cessation program if the child's
      doctor offered it to them. In contrast, of the 122 smoking parents who
      accompanied their child to the doctor in the past year, only 11 (9%) had any
      counseling recommended to them, and only 1 (0.8%) was actually enrolled. These
      results did not vary by parent age, gender, race, or child age. CONCLUSIONS: When
      interacting with parents who smoke, child health care providers have low rates of
      referring and enrolling parents in any services related to smoking. Enrollment in
      quitlines would be acceptable to the majority of parents in the context of their
      child's health care visit. Tobacco control efforts in the child health care
      setting should include implementation of office systems that can facilitate
      enrollment of parental smokers in telephone quitlines.

PMID- 16585284
TI  - Complementary feeding adequacy in relation to nutritional status among early
      weaned breastfed children who are born to HIV-infected mothers: ANRS 1201/1202
      Ditrame Plus, Abidjan, Cote d'Ivoire.
AB  - OBJECTIVE: In high HIV prevalence resource-constrained settings, exclusive
      breastfeeding with early cessation is one of the conceivable interventions aimed
      at the prevention of HIV through breast milk. Nevertheless, this intervention has
      potential adverse effects, such as the inappropriateness of complementary feeding
      to take over breast milk. The purpose of our study first was to describe the
      nature and the ages of introduction of complementary feeding among early weaned
      breastfed infants up to their first birthday and second was to assess the
      nutritional adequacy of these complementary foods by creating a child feeding
      index and to investigate its association with child nutritional status. METHODS:
      A prospective cohort study in Abidjan, Cote d'Ivoire, was conducted in HIV
      infected pregnant women who were willing to breastfeed and had received a
      perinatal antiretroviral prophylaxis. They were requested to practice exclusive
      breastfeeding and initiate early cessation of breastfeeding from the fourth month
      to reduce breast milk HIV transmission. Nature and ages of introductory
      complementary feeding were described in infants up to their first birthday by
      longitudinal compilation of 24-hour and 7-day recall histories. These recalls
      were done weekly until 6 weeks of age, monthly until 9 months of age, and then
      quarterly. We created an index to synthesize the nutritional adequacy of infant
      feeding practices (in terms of quality of the source of milk, dietary diversity,
      food, and meal frequencies) ranging from 0 to 12. The association of this feeding
      index with growth outcomes in children was investigated. RESULTS: Among the 262
      breastfed children included, complete cessation of breastfeeding occurred in 77%
      by their first birthday, with a median duration of 4 months. Most of the
      complementary foods were introduced within the seventh month of life, except for
      infant food and infant formula that were introduced at age 4 months. The feeding
      index was relatively low (5 of 12) at age 6 months, mainly as a result of
      insufficient dietary diversity, but was improved in the next 6 months (8.5 of 12
      at 12 months of age). Inadequate complementary feeding at age 6 months was
      associated with impaired growth during the next 12 months, with a 37% increased
      probability of stunting. CONCLUSION: Adequate feeding practices around the
      weaning period are crucial to achieving optimal child growth. HIV-infected women
      should turn to early cessation of breastfeeding only when they are counseled
      properly to provide adequate complementary feeding to take over breast milk. Our
      child feeding index could contribute to the assessment of the nutritional
      adequacy of complementary feeding around the weaning period and therefore help to
      detect children who are at risk for malnutrition.

PMID- 16585285
TI  - Comparison of techniques to evaluate adiposity in stunted and nonstunted
      children.
AB  - OBJECTIVE: The use of anthropometric measures (eg, skinfold thicknesses, BMI) to
      assess obesity is not without controversy and has not been explored with respect
      to the use among groups of children with growth retardation (ie, stunting).
      Therefore, the objective of this study was to determine whether growth
      retardation affects the accuracy of field methods for assessing body composition
      in children. METHODS: A cross-sectional study was conducted in 30 stunted
      children and 30 nonstunted children who were matched for age- and weight-for
      height z score and living in the shantytowns of Sao Paulo, Brazil. Body
      composition (fat mass, fat-free mass, and percentage of body fat [%BF]) was
      measured by H2(18)O dilution (reference technique) using group-specific values
      for the hydration of fat-free mass and dual-energy x-ray absorptiometry. BMI and
      body composition that were calculated from 3 pediatric skinfold prediction
      equations were evaluated for accuracy of %BF in comparison with the reference
      technique. RESULTS: Stunted children were shorter and weighed less than
      nonstunted children, but BMI did not differ significantly between groups. All 3
      skinfold equations tested resulted in a calculated %BF that was significantly
      lower than that measured by H2(18)O dilution for both stunted and nonstunted
      groups, and %BF as calculated by any of the skinfold equations tested did not
      significantly predict %BF by H2(18)O dilution. In contrast, BMI significantly
      predicted %BF in both stunted and nonstunted children, and this relationship did
      not differ by growth status. CONCLUSION: BMI but not skinfolds significantly
      predicted %BF measured by H2(18)O dilution. The relationship between BMI and %BF
      did not differ between stunted and nonstunted children; this indicates that BMI
      can be used in field studies of obesity and stunting. However, the prediction of
      %BF by BMI is relatively poor in both groups of children, and continued
      investigation of more accurate field methods for measuring %BF is warranted.

PMID- 16585286
TI  - Enrolling vulnerable, uninsured but eligible children in public health insurance:
      association with health status and primary care access.
AB  - OBJECTIVES: Given that more than two thirds of uninsured children in California
      are eligible for public health insurance coverage, this study examined
      differences in primary care access and health status between uninsured but
      eligible (UBE) children and those who were insured. METHODS: Using data on 19485
      children from the 2001 California Health Interview Survey, this study examined
      differences in primary care access and health status for UBE children versus
      those who were enrolled in public coverage. Results are stratified by profiles of
      other risk factors (RF) for poor access: nonwhite, low income, low parent
      education, and non-English speaking. RESULTS: UBE children were less likely than
      publicly enrolled children to have a physician visit in the past year, dental
      visit in the past year, and a regular source of care. On the basis of differences
      between the UBE children and enrollees in the prevalence of each dependent
      measure, UBE children with multiple RFs experienced greater disparities than UBE
      children with fewer RFs. For example, enrollees were more likely than UBE
      children to have a regular source of care among children with 2, 3, or 4 RFs
      (differences of 26, 26, and 25 percentage points, respectively) compared with 1
      RF (19 percentage points) and 0 RFs (12 percentage points). A similar pattern was
      found for dental visits but not physician visits. Although there was no
      difference in health status between UBE children and enrollees overall, enrollees
      were more likely than UBE children to have excellent/very good health status
      among children with 2 RFs (difference of 9 percentage points), 3 RFs (12
      percentage points), and 4 RFs (11 percentage points). CONCLUSIONS: This study
      demonstrates that UBE children in California have poorer access to care compared
      with enrollees, and those with the highest levels of risk have poorer health
      status. This suggests that providing insurance to these children (and
      particularly those with multiple RFs) may lead to improved access and health for
      these vulnerable children.

PMID- 16585287
TI  - Rectal bleeding in infancy: clinical, allergological, and microbiological
      examination.
AB  - OBJECTIVE: Rectal bleeding is an alarming symptom and requires additional
      investigation. In infants it has been explained mainly by hypersensitivity. In
      addition to dietary antigens, intraluminal microbial agents challenge the
      immature gut mucosa. Although controlled in the mature gut, these antigens may
      induce inflammation in the developing gastrointestinal tract. The objectives of
      this study were to evaluate prospectively the clinical course of rectal bleeding
      and evaluate the impact of cow's milk allergy and aberrant gut microbiota on the
      condition. Because withdrawal of cow's milk antigens from the infants' diet is
      used as a first treatment without evidence of its efficacy, we also aimed to
      asses the effect of a cow's milk-elimination diet on the duration of rectal
      bleeding. METHODS: The study involved 40 consecutive infants (mean age: 2.7
      months) with visible rectal bleeding during a 2-year period at the Tampere
      University Hospital Department of Pediatrics. Most of the infants (68%) were
      fully breastfed. At enrollment the infants were randomly allocated to receive a
      cow's milk-elimination diet (n = 19) or continue their previous diet (n = 21) for
      1 month. Findings of colonoscopy, fecal bacterial culture, fluorescence in situ
      hybridization of selected gut genera, specific detection of fecal enteroviruses,
      rotaviruses, and adenoviruses, fecal electron microscopy for viruses, and mucosal
      electron microscopy for viruses were assessed. During each visit the severity of
      atopic eczema, if any, was assessed according to the SCORAD method. In evaluating
      the extent of sensitization, serum total immunoglobulin E (IgE) and specific IgE
      and skin-prick tests for cow's milk, egg, and wheat were studied. Cow's milk
      allergy was diagnosed by elimination and provocation testing. Five patients were
      hospitalized; all others were treated on an outpatient basis. The follow-up
      visits were scheduled 1 month later and at the age of 1 year. Sixty-four healthy
      reference infants were selected as controls according to the following criteria:
      age and timing of fecal sampling being identical to within 1 month. RESULTS:
      Altogether, 32 (80%) infants manifested bloody stools during follow-up (mean
      [range]: 2.1 [1-15] per day). The mean number of days with rectal bleeding on
      follow-up was 6. Typically, bloody stools occurred irregularly, for which reason
      the mean time to the last occurrence of rectal bleeding was 24 (range: 1-85) days
      from admission. Atopic eczema at presentation or during follow-up was diagnosed
      in 38% of the infants. Increased specific IgE concentrations or a positive skin
      prick test were uncommon. The growth of the infants was normal on admission and
      during follow-up. Colonoscopy revealed typically focal mucosal erythema and
      aphthous ulcerations. The mucosa appeared normal in less than half of the
      patients. No anorectal fissures or colonic polyps were found. Light microscopy
      revealed that the overall architecture of the mucosa was well maintained. Acute
      inflammation or postinflammatory state and focal infiltration of eosinophils in
      the lamina propria were the most common abnormalities. A cow's milk-elimination
      diet did not affect the duration of rectal bleeding. Cow's milk allergy was
      diagnosed in 7 (18%) patients. Virus-particle aggregates were found in the
      microvillus layer of the colon epithelium in 8 cases. The surface epithelium of
      the virus-positive colon biopsy specimens regularly showed degenerative changes
      in the microvillus layer and epithelial cells. Electron microscopy study of the
      colon biopsies disclosed virus particles (30 nm in diameter) on the surface of
      epithelial cells. Virus particles or RNA were present in feces in only a minority
      of the patients. All fecal cultures were negative for Salmonella, Shigella, and
      Yersinia. Campylobacter jejuni was found in the feces of 1 patient, and fecal
      cultures were positive for Clostridium difficile in 4 patients, Staphylococcus
      aureus in 8 patients, and yeast in 2 patients. Fluorescence in situ hybridization
      revealed that at the time of admission the total numbers of bacteria and the
      numbers of bifidobacteria and lactobacilli in feces were lower in the patients
      compared with controls. The fecal concentrations of microbes characterized in
      this study (Bacteroides, bifidobacteria, Clostridium, lactobacilli, and
      enterococci) did not differ significantly between the time of admission and the
      second visit in the patients or controls. At the age of 1 year, 7 patients still
      suffered from cow's milk allergy, 5 of whom also suffered from multiple food
      allergies. Atopic eczema and histopathologically confirmed inflammation of the
      colonic mucosa at presentation were associated with persistence of cow's milk
      allergy at the age of 1 year. No patients exhibited gastrointestinal complaints
      or visible blood in stools. CONCLUSIONS: Rectal bleeding in infants is generally
      a benign and self-limiting disorder. Bloody stools occurred irregularly for only
      a few days during the following months. As in a previous report, most infants
      were exclusively breastfed. In the majority of the patients the cause of the
      condition remains unknown. An association with viruses can be seen in some
      patients. The microbes that commonly lead to bloody diarrhea in older children
      and adults, Salmonella, Shigella, and Yersinia, were absent in the present
      material. The low bifidobacterial numbers in fecal samples may indicate a
      significant aberrance that may provide a target for probiotic intervention to
      normalize gut microbiota. The gut microbiota overall seemed stable, because the
      numbers of major groups of microbiota tested did not change significantly between
      the time of admission and after 1 month. Cow's milk allergy among these patients
      is more uncommon than previously believed. Cow's milk challenge is thus essential
      in infants who become symptom-free during a cow's milk-free diet to reduce the
      number of false-positive cow's milk-allergy diagnoses.

PMID- 16585289
TI  - Breastfeeding does not increase the risk of asthma at 14 years.
AB  - OBJECTIVES: There are conflicting data regarding the impact of breastfeeding on
      the development of asthma in late childhood. Our aim with this study was to
      investigate the relationship between breastfeeding and the prevalence of asthma
      in children at 14 years. METHODS: The Mater-University of Queensland Study of
      Pregnancy is a birth cohort of 7223 women and their infants recruited from a
      public antenatal clinic in Brisbane, Australia, between 1981 and 1984. Data
      regarding breastfeeding and the duration of breastfeeding were collected through
      the use of a questionnaire completed by the mother 6 months postdelivery, and the
      prevalence of asthma was determined through the use of a questionnaire completed
      by the mother 14 years postdelivery. RESULTS: Data regarding both breastfeeding
      and asthma were available for 4964 children. The prevalence of asthma in children
      at 14 years was 28.4%. Breastfeeding for > or =4 months was not found to have a
      significant effect on the prevalence of asthma in 14-year-olds. The unadjusted
      odds ratio of developing asthma at 14 years if the child was breastfed for > or
      =4 months was 1.03. The odds ratio of developing asthma did not change
      appreciably when allowance was made for potential confounding factors.
      CONCLUSION: Data from this study indicate that breastfeeding neither increases
      nor decreases the prevalence of asthma in children at 14 years.

PMID- 16585288
TI  - Sleep-disordered breathing, behavior, and cognition in children before and after
      adenotonsillectomy.
AB  - OBJECTIVES: Most children with sleep-disordered breathing (SDB) have mild-to
      moderate forms, for which neurobehavioral complications are believed to be the
      most important adverse outcomes. To improve understanding of this morbidity, its
      long-term response to adenotonsillectomy, and its relationship to
      polysomnographic measures, we studied a series of children before and after
      clinically indicated adenotonsillectomy or unrelated surgical care. METHODS: We
      recorded sleep and assessed behavioral, cognitive, and psychiatric morbidity in
      105 children 5.0 to 12.9 years old: 78 were scheduled for clinically indicated
      adenotonsillectomy, usually for suspected SDB, and 27 for unrelated surgical
      care. One year later, we repeated all assessments in 100 of these children.
      RESULTS: Subjects who had an adenotonsillectomy, in comparison to controls, were
      more hyperactive on well-validated parent rating scales, inattentive on cognitive
      testing, sleepy on the Multiple Sleep Latency Test, and likely to have attention
      deficit/hyperactivity disorder (as defined by the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition) as judged by a child psychiatrist. In
      contrast, 1 year later, the 2 groups showed no significant differences in the
      same measures. Subjects who had an adenotonsillectomy had improved substantially
      in all measures, and control subjects improved in none. However, polysomnographic
      assessment of baseline SDB and its subsequent amelioration did not clearly
      predict either baseline neurobehavioral morbidity or improvement in any area
      other than sleepiness. CONCLUSIONS: Children scheduled for adenotonsillectomy
      often have mild-to-moderate SDB and significant neurobehavioral morbidity,
      including hyperactivity, inattention, attention-deficit/hyperactivity disorder,
      and excessive daytime sleepiness, all of which tend to improve by 1 year after
      surgery. However, the lack of better correspondence between SDB measures and
      neurobehavioral outcomes suggests the need for better measures or improved
      understanding of underlying causal mechanisms.

PMID- 16585290
TI  - Severe methemoglobinemia complicating topical benzocaine use during endoscopy in
      a toddler: a case report and review of the literature.
AB  - Severe methemoglobinemia resulting from the use of topical benzocaine has been
      reported in adults as a rare complication. Here we report a case of severe
      acquired methemoglobinemia resulting from topical use of benzocaine spray during
      diagnostic upper gastrointestinal endoscopy in a 3-year-old boy with repeated
      episodes of hematemesis 3 weeks posttonsillectomy. He developed marked cyanosis
      and became increasingly agitated immediately after completion of his unremarkable
      endoscopic procedure, which was performed under intravenous sedation. He did not
      respond to maximum supplemental oxygen and had increased respiratory effort. His
      pulse oximetry dropped to 85%, but simultaneous arterial blood-gas analysis
      showed marked hypoxemia (Po2 = 29%) and severe methemoglobinemia (methemoglobin =
      39%). His cyanosis and altered mental status promptly resolved after intravenous
      administration of methylene blue. In patients with methemoglobinemia, pulse
      oximetry tends to overestimate the actual oxygen saturation and is not entirely
      reliable. Posttonsillectomy bleeding is a rare but occasionally serious
      complication that could occur weeks after the surgery, although it more commonly
      occurs within the first few days. Physicians should remain aware of the
      possibility of its late onset. This case illustrates the severity of acquired
      methemoglobinemia that may result from even small doses of topical benzocaine and
      highlights the fact that prompt treatment of the disorder can be life saving. We
      question the rationale for routine use of topical anesthetic spray for sedated
      upper gastrointestinal endoscopy in children. By bringing the attention of
      pediatricians to this rare but serious complication, we hope that it will result
      in its improved recognition and possible prevention.

PMID- 16585291
TI  - Multifocal lymphangioendotheliomatosis with thrombocytopenia: a rare cause of
      gastrointestinal bleeding in the newborn period.
AB  - Severe gastrointestinal bleeding in the newborn period is a serious but uncommon
      phenomenon that has a broad differential diagnosis. In the following case report
      we describe a rare phenomenon in which a newborn presents with severe
      hematemesis, hematochezia, and thrombocytopenia that are resistant to repeated
      platelet and packed red blood cell transfusions. Previous cases have been
      reported, but none of the patients described presented within the first 8 days of
      life. The early age of presentation and refractory nature of this disease entity
      to multiple therapies make it a diagnostic and therapeutic dilemma for all
      physicians involved in the care of newborns.

PMID- 16585292
TI  - Bloody nipple discharge in an infant and a proposed diagnostic approach.
AB  - Bloody nipple discharge is a rare finding in infants and is associated most often
      with benign mammary duct ectasia. The rarity of this symptom in infants and its
      association with breast carcinoma in adults can lead to unnecessary investigation
      and treatment. Here we describe a 4-month-old boy with bilateral bloody nipple
      discharge that resolved spontaneously without treatment by 6 months of age.
      Furthermore, we propose a strategic method for the evaluation of such infants.

PMID- 16585293
TI  - Uptake of varicella vaccination among young children in the United States: a
      success story in eliminating racial and ethnic disparities.
AB  - OBJECTIVE: To examine uptake of varicella vaccine, a live attenuated vaccine
      licensed in 1995 and recommended in 1996 for routine vaccination of US children
      12 to 18 months of age. METHODS: Data were for 178,616 children (19-35 months of
      age) and were collected in the 1997 to 2004 National Immunization Survey. The
      main outcome measures were estimated varicella vaccine coverage from 1997 to
      2004, coverage among susceptible children (ie, those without a history of
      varicella disease), racial/ethnic disparities, risk factors for nonvaccination,
      missed opportunities to vaccinate simultaneously with other recommended vaccines,
      and projected increases in coverage after elimination of missed opportunities for
      simultaneous vaccination. RESULTS: Varicella vaccine coverage rates increased
      from 26% in 1997 to 87% in 2004. State-specific coverage rates increased 44 to 80
      percentage points and were >80% in 42 states and >90% in 13 states by 2004.
      Coverage among susceptible children increased from 62% in 1999 to 88% in 2004.
      From 1998 onward, no statistically significant differences in coverage were found
      between white and black children, whereas Hispanic children had higher coverage
      rates than white children in 1998 to 2001 and 2004. Risk factors for
      undervaccination included living in the Midwest region, living in a household
      with >1 child, living in nonmetropolitan areas, living below the poverty level,
      having a mother who did not have a college degree, and having public providers.
      If missed opportunities for simultaneous vaccination had been eliminated, then
      coverage rates would have increased from 58% to 94% in 1999 and from 87% to 96%
      in 2004. CONCLUSIONS: Uptake of varicella vaccine has been steady and is an
      example of successful elimination of racial and ethnic disparities. Additional
      focus should be placed on reducing missed opportunities for simultaneous
      vaccination, improving coverage in rural areas and the Midwest region, and
      closing remaining gaps related to maternal education, provider type, and multiple
      children households.

PMID- 16585294
TI  - Effectiveness of Centers for Disease Control and Prevention recommendations for
      outcomes of acute otitis media.
AB  - OBJECTIVES: To determine whether we could increase adherence to the Centers for
      Disease Control and Prevention (CDC) recommendations with well-accepted
      approaches to improving quality of care and adherence to the CDC recommendations
      resulted in improved outcomes for acute otitis media (AOM). METHODS: A cluster
      randomization study was conducted in 12 pediatric practices (6 intervention and 6
      control sites). The main outcome measures were adherence to the CDC
      recommendations (modified to include 2 additional antimicrobial agents) and a
      subsequent antibiotic prescription for AOM within 30 days after diagnosis.
      RESULTS: Of 3152 patients referred to research assistants, 2584 (82%) were
      eligible. Of those eligible, 1368 (99%) of 1382 at the intervention sites and
      1138 (99%) of 1146 at the control sites consented to participate. Rates of
      adherence to the CDC recommendations were not significantly higher at the
      intervention sites than at the control sites, for initial enrollment episodes
      (78.2% vs 70.6%) or second episodes (62.6% vs 59.9%). After controlling for
      clustering according to site and covariates, children who were not treated in
      adherence to the CDC recommendations for both episodes had 1.60 times the odds of
      a subsequent prescription within 12 days, compared with those treated in
      adherence at both episodes. CONCLUSIONS: Despite using evidence-based approaches
      that are known to influence physician behavior, we were unable to increase
      adherence to the CDC recommendations for treatment of AOM. However, we did
      establish that prescription of antimicrobial therapy consistent with the CDC
      recommendations for a second episode of AOM was associated with improved
      outcomes, measured as the need for subsequent antibiotic prescription. Because of
      the selection of resistant otopathogens, adherence to the CDC recommendations is
      likely more important in subsequent episodes of AOM than in the initial episode.

PMID- 16585295
TI  - Sexy media matter: exposure to sexual content in music, movies, television, and
      magazines predicts black and white adolescents' sexual behavior.
AB  - OBJECTIVE: To assess over time whether exposure to sexual content in 4 mass media
      (television, movies, music, and magazines) used by early adolescents predicts
      sexual behavior in middle adolescence. METHODS: An in-home longitudinal survey of
      1017 black and white adolescents from 14 middle schools in central North Carolina
      was conducted. Each teen was interviewed at baseline when he or she was 12 to 14
      years old and again 2 years later using a computer-assisted self interview (audio
      computer-assisted self-interview) to ensure confidentiality. A new measure of
      each teen's sexual media diet (SMD) was constructed by weighting the frequency of
      use of 4 media by the frequency of sexual content in each television show, movie,
      music album, and magazine the teen used regularly. RESULTS: White adolescents in
      the top quintile of sexual media diet when 12 to 14 years old were 2.2 times more
      likely to have had sexual intercourse when 14 to 16 years old than those who were
      in the lowest SMD quintile, even after a number of other relevant factors,
      including baseline sexual behavior, were introduced. The relationship was not
      statistically significant for black adolescents after controlling for other
      factors that were more predictive, including parental disapproval of teen sex and
      perceived permissive peer sexual norms. CONCLUSIONS: Exposure to sexual content
      in music, movies, television, and magazines accelerates white adolescents' sexual
      activity and increases their risk of engaging in early sexual intercourse. Black
      teens appear more influenced by perceptions of their parents' expectations and
      their friends' sexual behavior than by what they see and hear in the media.

PMID- 16585296
TI  - The contribution of diagnostic substitution to the growing administrative
      prevalence of autism in US special education.
AB  - OBJECTIVE: Growing administrative prevalence of autism has stirred public
      controversy and concern. The extent to which increases in the administrative
      prevalence of autism have been associated with corresponding decreases in the use
      of other diagnostic categories is unknown. The main objective of this study was
      to examine the relationship between the rising administrative prevalence of
      autism in US special education and changes in the use of other classification
      categories. METHODS: The main outcome measure was the administrative prevalence
      of autism among children ages 6 to 11 in US special education. Analysis involved
      estimating multilevel regression models of time-series data on the prevalence of
      disabilities among children in US special education from 1984 to 2003. RESULTS:
      The average administrative prevalence of autism among children increased from 0.6
      to 3.1 per 1000 from 1994 to 2003. By 2003, only 17 states had a special
      education prevalence of autism that was within the range of recent
      epidemiological estimates. During the same period, the prevalence of mental
      retardation and learning disabilities declined by 2.8 and 8.3 per 1000,
      respectively. Higher autism prevalence was significantly associated with
      corresponding declines in the prevalence of mental retardation and learning
      disabilities. The declining prevalence of mental retardation and learning
      disabilities from 1994 to 2003 represented a significant downward deflection in
      their preexisting trajectories of prevalence from 1984 to 1993. California was
      one of a handful of states that did not clearly follow this pattern. CONCLUSIONS:
      Prevalence findings from special education data do not support the claim of an
      autism epidemic because the administrative prevalence figures for most states are
      well below epidemiological estimates. The growing administrative prevalence of
      autism from 1994 to 2003 was associated with corresponding declines in the usage
      of other diagnostic categories.

PMID- 16585297
TI  - Current asthma guidelines may not identify young children who have experienced
      significant morbidity.
AB  - BACKGROUND: The current guideline for classifying asthma severity, the National
      Asthma Education Prevention Program (NAEPP) 2002, is not evidence-based. We had
      the opportunity to validate this guideline in an untreated inner-city population,
      both in those < or =5 and those >5 years of age. The basis for this retrospective
      validation model was to determine how well the NAEPP severity classification
      based on symptom-frequency criteria alone identified patients in those age groups
      demonstrating significant morbidity the previous year and thus the potential need
      for controller therapy. METHODS: Using a mobile asthma van (Breathmobile) at the
      school site, children not receiving controller medication were evaluated by an
      asthma specialist for severity according to NAEPP guideline clinical criteria.
      Validation was determined by the relationship of guideline severity to > or =2
      emergency department (ED) visits, any hospitalization, health care utilization
      (any ED visit, hospitalization), number of exacerbations, and school absenteeism
      resulting from asthma the prior year. RESULTS: Eight hundred twenty-six asthmatic
      children were evaluated; 89 (10.8%) were < or =2 years, 222 (26.9%) were 3 to 5
      years, and 515 (62.3%) were >5 years of age; 60.5% were male, and 80.9% were
      Hispanic. Classification of asthma severity included 34.4% with mild
      intermittent, 10.2% with mild persistent, 31.5% with moderate persistent, and
      24.0% with severe persistent asthma categories. There were significantly more
      Hispanic children and children < or =5 years classified as having mild
      intermittant asthma. Morbidity was clearly related to severity in the overall
      population. However, although the health care utilization was significantly
      related to severity, it was borderline in those 3 to 5 years and nonsignificant
      in children < or =2 years. CONCLUSIONS: The NAEPP guidelines 2002, based on
      symptom-frequency criteria as assessed in this study, seem to offer a valid basis
      for classifying asthma severity in those >5 years of age but may underclassify
      younger children. Our data suggest that morbidity experienced in the prior year
      may provide a useful additional criterion for classifying asthma severity,
      particularly in those children < or =5 years of age.

PMID- 16585298
TI  - A randomized, controlled trial of an interactive educational computer package for
      children with asthma.
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact and acceptability
      of an educational multimedia program designed to promote self-management skills
      in children with asthma. METHODS: We conducted a randomized, controlled trial
      with measures at baseline and 1- and 6-month follow-up. The trial was conducted
      in pediatric outpatient respiratory clinics in 3 United Kingdom hospitals.
      Participants included 101 children aged 7 to 14 years under the care of hospital
      based asthma services. The children were randomly assigned to receive an asthma
      information booklet alone or the booklet plus The Asthma Files, an interactive CD
      ROM for children with asthma. Asthma knowledge was the primary outcome measure.
      Other measures included asthma locus of control, lung function, use of oral
      steroids, and school absence. RESULTS: At the 1-month follow-up (n = 99),
      children in the computer group had improved knowledge compared with the control
      group and a more internal locus of control. There were no differences in
      objective lung-function measures, hospitalizations, or oral steroid use. The
      study participants were positive in their evaluation of the intervention. At the
      6-month follow-up (n = 90), significantly fewer children in the intervention
      group had required oral steroids and had had time off school for asthma in the
      previous 6 months. The difference did not reach statistical significance in the
      intention-to-treat analysis for both steroid use and school absence. CONCLUSION:
      The Asthma Files was found to be an effective and popular health education tool
      for promoting asthma self-management skills within pediatric care.

PMID- 16585299
TI  - Rapid tests for group B Streptococcus colonization in laboring women: a
      systematic review.
AB  - OBJECTIVES: We set out to determine the accuracy and rapidity of various
      intrapartum group B Streptococcus (GBS) colonization tests. STUDY DESIGN: We
      performed a systematic review of test-accuracy studies, which were identified
      without language restriction from Medline and Cochrane databases; bibliographies
      of known primary and review articles; and contact with authors, experts, and
      manufacturers. Studies were selected if they tested pregnant women intrapartum
      for GBS colonization and confirmed by "gold-standard" laboratory cultures. Two
      reviewers independently selected studies and extracted data on their
      characteristics, quality, and results. Accuracy data were used to form 2 x 2
      contingency tables. Heterogeneity was assessed, and LRs for positive and negative
      test results were pooled in subgroups of studies of various tests. RESULTS: There
      were 29 test-accuracy studies in 15,691 women, evaluating 6 different tests:
      polymerase chain reaction (PCR), optical immunoassay (OIA), DNA hybridization,
      enzyme immunoassay, latex agglutination, and Islam starch medium tests. The
      methodologic quality of the studies was generally poor. The most accurate was the
      real-time PCR test, but it was less rapid than OIA test. Real-time PCR took 40
      minutes to complete, whereas the OIA took 30 minutes. CONCLUSIONS: Real-time PCR
      and OIA are candidates for rapid near patient intrapartum GBS testing to
      determine the need for antibiotic prophylaxis to prevent neonatal GBS disease.
      Before implementation in practice, a robust technology assessment of their
      accuracy, acceptability, and cost-effectiveness is required.

PMID- 16585300
TI  - The role of parental preferences in the management of fever without source among
      3- to 36-month-old children: a decision analysis.
AB  - OBJECTIVES: Recent analyses assessing the impact of the conjugate pneumococcal
      vaccine on the care of febrile children do not reflect the role parental
      preferences play in physicians' decisions. The objective of this study was to
      identify the management strategy that would best suit parents, on the basis of
      their values for possible outcomes of fever of > or =39 degrees C without source
      among well-appearing, 3- to 36-month-old children. METHODS: A decision analysis
      was performed to compare the benefits and outcomes of 3 management options
      (treat: blood culture and antibiotics for all children; test: blood culture and
      complete blood count for all children, with antibiotics for selected children;
      observe: no immediate intervention). A hypothetical cohort of 100,000 children
      with fever of > or =39 degrees C with no obvious source of infection was modeled
      for each strategy. Using this model, we identified the treatment option that
      would best suit each parent's preferences, on the basis of parental utilities
      (from a prior study) for various interventions and outcomes at vaccine efficacies
      of 0% (ie, no vaccine) and 95%. In addition, we performed survival analyses to
      assess the morbidity and mortality rates associated with each treatment strategy
      at various vaccine efficacies. RESULTS: At a vaccine efficacy of 0%, the majority
      of parents' preferences suggested the treat option, the strategy with the lowest
      mortality rate. At a vaccine efficacy of 95%, mortality rates were similar for
      all 3 management options (approximately 1 in 100,000), but parental preferences
      were still aligned with different options; 50% suggested observe, 42% suggested
      test, and 8% suggested treat. CONCLUSIONS: Like physicians, parents have
      different approaches to risk. With the conjugate pneumococcal vaccine, risks of
      complications from fever without source are low regardless of treatment strategy.
      Rather than having a "one size fits all" approach, it is reasonable to
      incorporate parental preferences into the treatment decision.

PMID- 16585301
TI  - Oral sildenafil in infants with persistent pulmonary hypertension of the newborn:
      a pilot randomized blinded study.
AB  - BACKGROUND: Persistent pulmonary hypertension (PPHN) occurs in as many as 6.8 of
      1000 live births. Mortality is approximately 10% to 20% with high-frequency
      ventilation, surfactant, inhaled nitric oxide, and extracorporeal membrane
      oxygenation but is much higher when these therapies are not available. Sildenafil
      is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary
      vascular resistance. OBJECTIVE: Our goal was to evaluate the feasibility of using
      oral sildenafil and its effect on oxygenation in PPHN. DESIGN: This study was a
      proof-of-concept, randomized, masked study in infants >35.5 weeks' gestation and
      <3 days old with severe PPHN and oxygenation index (OI) >25 admitted to the NICU
      (Hospital Nino Jesus, Barranquilla, Colombia). The sildenafil solution was
      prepared from a 50-mg tablet. The first dose (1 mg/kg) or placebo was given by
      orogastric tube <30 minutes after randomization and every 6 hours. Preductal
      saturation and blood pressure were monitored continuously. OI was calculated
      every 6 hours. The main outcome variable was the effect of oral sildenafil on
      oxygenation. Sildenafil or placebo was discontinued when OI was <20 or if there
      was no significant change in OI after 36 hours. RESULTS: Six infants with an OI
      of >25 received placebo, and 7 received oral sildenafil at a median age of 25
      hours. All infants were severely ill, on fraction of inspired oxygen 1.0, and
      with similar ventilatory parameters. Intragastric sildenafil and placebo were
      well tolerated. In the treatment group, OI improved in all infants within 6 to 30
      hours, all showed a steady improvement in pulse oxygen saturation over time, and
      none had noticeable effect on blood pressure; 6 of 7 survived. In the placebo
      group, 1 of 6 infants survived. CONCLUSIONS: Oral sildenafil was administered
      easily and tolerated as well as placebo and improved OI in infants with severe
      PPHN, which suggests that oral sildenafil may be effective in the treatment of
      PPHN and underscores the need for a large, controlled trial.

PMID- 16585302
TI  - Acellular pertussis vaccine booster combined with diphtheria and tetanus toxoids
      for adolescents.
AB  - BACKGROUND: The incidence of pertussis is increasing, especially in adolescents,
      attributed in part to waning of immunity after childhood immunization. Recently
      licensed in the United States for use in adolescents, acellular pertussis
      vaccines will provide an immunogenic and safe option for booster immunization
      against pertussis. METHODS: This prospective, randomized, observer-blinded,
      multicenter, comparative study evaluated the safety and immunogenicity of a
      vaccine formulated with tetanus toxoid, reduced diphtheria toxoid, and acellular
      pertussis antigens (Tdap) compared with tetanus and diphtheria toxoids vaccine
      (Td) for booster immunization in adolescents. There were 4114 healthy adolescents
      aged 10 to 18 years who completed childhood vaccination against diphtheria,
      tetanus, and pertussis who were enrolled, randomized, and received study vaccine.
      RESULTS: Local and general symptoms were comparable between the Tdap and Td
      groups. The immune response of Tdap was comparable with Td vaccine for tetanus
      and diphtheria seroprotection and booster responses. In addition, geometric mean
      concentrations of antibody to pertussis antigens, pertussis toxoid, filamentous
      hemagglutinin, and pertactin exceeded the antibody response elicited after infant
      immunization with diphtheria and tetanus toxoids and acellular pertussis antigens
      (DTaP) that had proven efficacy against pertussis. CONCLUSIONS: In adolescents,
      the studied Tdap was safe and immunogenic and induced pertussis antibodies that
      were higher than those associated with efficacy in infants.

PMID- 16585303
TI  - Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures,
      blood cultures, and cerebrospinal fluid parameters?
AB  - BACKGROUND: Meningitis is a substantial cause of morbidity and mortality in
      neonates. Clinicians frequently use the presence of positive blood cultures to
      determine whether neonates should undergo lumbar puncture. Abnormal cerebrospinal
      fluid (CSF) parameters are often used to predict neonatal meningitis and
      determine length and type of antibiotic therapy in neonates with a positive blood
      culture and negative CSF culture. METHODS: We evaluated the first lumbar puncture
      of 9111 neonates at > or =34 weeks' estimated gestational age from 150 NICUs,
      managed by the Pediatrix Medical Group, Inc. CSF culture results were compared
      with results of blood cultures and CSF parameters (white blood cells [WBCs],
      glucose, and protein) to establish the concordance of these values in culture
      proven meningitis. CSF cultures positive for coagulase-negative staphylococci and
      other probable contaminants, as well as fungal and viral pathogens, were excluded
      from analyses. RESULTS: Meningitis was confirmed by culture in 95 (1.0%)
      neonates. Of the 95 patients with meningitis, 92 had a documented blood culture.
      Only 57 (62%) of 92 patients had a concomitant-positive blood culture; 35 (38%)
      of 92 had a negative blood culture. In neonates with both positive blood and CSF
      cultures, the organisms isolated were discordant in 2 (3.5%) of 57 cases. In each
      case, the CSF pathogen required different antimicrobial therapy than the blood
      pathogen. For culture-proven meningitis, CSF WBC counts of >0 cells per mm3 had
      sensitivity at 97% and specificity at 11%. CSF WBC counts of >21 cells per mm3
      had sensitivity at 79% and specificity at 81%. Culture-proven meningitis was not
      diagnosed accurately by CSF glucose or by protein. CONCLUSIONS: Neonatal
      meningitis frequently occurs in the absence of bacteremia and in the presence of
      normal CSF parameters. No single CSF value can reliably exclude the presence of
      meningitis in neonates. The CSF culture is critical to establishing the diagnosis
      of neonatal meningitis.

PMID- 16585304
TI  - The economic costs of congenital bilateral permanent childhood hearing
      impairment.
AB  - OBJECTIVE: The objective of this study was to estimate the economic costs of
      bilateral permanent childhood hearing impairment (PCHI) in the preceding year of
      life for children aged 7 to 9 years. METHODS: A cost analysis was conducted by
      using a birth cohort of children born between 1992 and 1997 in 8 districts of
      Southern England, of which half had been born into populations exposed to
      universal newborn screening (UNS). Unit costs were applied to estimates of
      health, social, and broader resource use made by 120 hearing-impaired children
      and 63 children in a normally hearing comparison group. Associations between
      societal costs per child and severity of hearing impairment, language ability
      score, exposure to UNS, and age of confirmation were analyzed, including
      adjustment for potential confounders in a linear regression model. RESULTS: The
      mean societal cost in the preceding year of life at 7 to 9 years of age was
      14092.5 pound sterling for children with PCHI, compared with 4206.8 pound
      sterling for the normally hearing children, a cost difference of 9885.7 pound
      sterling. After adjusting for severity and other potential confounders in a
      linear regression model, mean societal costs among children with PCHI were
      reduced by 2553 pound sterling for each unit increase in the z score for
      receptive language. Using similar regression models, exposure to a program of UNS
      was associated with a smaller cost reduction of 2213.2 pound sterling, whereas
      costs were similar between children whose PCHI was confirmed at <9 or >9 months.
      CONCLUSIONS. The study provides rigorous evidence of the annual health, social,
      and broader societal cost of bilateral PCHI in the preceding year of life at 7 to
      9 years of age and shows that it is related to its severity and has an inverse
      relationship with language abilities after adjustment for severity.

PMID- 16585305
TI  - Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth
      weight of 1000 grams or less.
AB  - OBJECTIVE: Ductus arteriosus (DA) closure occurs within 96 hours in >95% of
      neonates >1500 g in birth weight (BW). The prevalence and postnatal age of
      spontaneous ductal closure in neonates < or =1000 g in BW (extremely low birth
      weight [ELBW] neonates) remain unclear, as does the incidence of failure to close
      with indomethacin. Therefore, we prospectively examined the prevalence, postnatal
      age, and clinical variables associated with spontaneous DA closure, occurrence of
      persistent patent DA, and indomethacin failure in ELBW neonates. METHODS:
      Neonates delivered at Parkland Memorial Hospital from February 2001 through
      December 2003 were studied. Those with congenital heart defects or death <10 days
      postnatally were excluded. Echocardiograms were performed 48 to 72 hours
      postnatal and every 48 hours until 10 days postnatally. RESULTS: We studied 122
      neonates with BW of 794 +/- 118 (SD) g and estimated gestational age (EGA) of 26
      +/- 2 weeks. Spontaneous permanent DA closure occurred in 42 (34%) neonates at
      4.3 +/- 2 days postnatally, with 100% closure by 8 days. These neonates were more
      mature, less likely to have received antenatal steroids or have hyaline membrane
      disease (HMD; 52% vs 79%), and more likely to be growth restricted (31% vs 5%)
      and delivered of hypertensive women. Using regression analysis, EGA and absence
      of antenatal steroids and HMD predicted ductal closure. Ten (8%) neonates with
      early DA closure reopened and required medical/surgical closure. Eighty neonates
      had persistent patent DA; 7 were surgically ligated, and 5 remained asymptomatic,
      with 4 of 5 closing after 10 days postnatally. Sixty-eight (85%) received
      indomethacin at 6.2 +/- 4 days postnatally; 41% failed therapy and had no
      distinguishing characteristics. CONCLUSIONS: Spontaneous permanent DA closure
      occurs in >34% of ELBW neonates and is predicted by variables related to
      maturation, for example, EGA and an absence of HMD, whereas indomethacin failure
      could not be predicated.

PMID- 16585306
TI  - Pediatric hospitalists: report of a leadership conference.
AB  - OBJECTIVES: To summarize a meeting of academic pediatric hospitalists and to
      describe the current state of the field. METHODS: The Ambulatory Pediatric
      Association sponsored a meeting for academic pediatric hospitalists in November
      2003. The purpose of the meeting was to discuss and to define roles of academic
      pediatric hospitalists, including their roles as clinicians, educators, and
      researchers, and to discuss organizational issues and unique hospitalist issues
      within general academic pediatrics. Workshops were held in the areas of
      organization and administration, academic life, research, and education. A
      literature review was also conducted in the areas discussed. RESULTS: More than
      130 physicians attended. Thirteen workshops were held, and all information was
      summarized in large-group sessions for all attendees. CONCLUSIONS: Pediatric
      hospital medicine is a rapidly growing field, with an estimated 800 to 1000
      pediatric hospitalists currently practicing. Initial work has defined the
      clinical environment and has begun to stake out a unique knowledge and skill set.
      The Pediatric Hospitalists in Academic Settings conference demonstrated the
      audience for additional development and the resources to move forward.

PMID- 16585307
TI  - Treated hypotension is associated with neonatal morbidity and hearing loss in
      extremely low birth weight infants.
AB  - BACKGROUND: Neonatal hypotension may be a risk factor for neurologic impairment.
      Few studies have examined the impact of low blood pressure in extremely low birth
      weight (ELBW) infants weighing 400 to 999 g on neurodevelopmental outcome.
      OBJECTIVES: We set out to explore the relationship between treated hypotension in
      the first 72 hours of life and perinatal factors, morbidity, and mortality in
      ELBW infants and then to compare neurosensory outcome in ELBW infants with
      treated hypotension and those who never received treatment for hypotension.
      DESIGN/METHODS: We performed chart review of all 156 ELBW infants admitted to our
      level III NICU in 1998-1999. Infants had "treated hypotension" if they received
      fluid pushes, corticosteroids, and/or vasopressors during the first 72 hours of
      life in an attempt to increase blood pressure. Follow-up included neurologic
      examination, Bayley Scales of Infant Development, vision and hearing evaluation.
      Statistical analysis was performed by using SPSS 11.0. Univariate and
      multivariate analyses were conducted to determine morbidities associated with
      treated hypotension. RESULTS: Fifty-nine infants received treatment for
      hypotension. Ninety-seven infants did not. The groups had similar race, gender,
      delivery mode, chorioamnionitis, and maternal socioeconomic status. Thirty-eight
      (24%) infants expired, including 20 who received treatment for hypotension. Of
      the 156 infants in the study group, 110 underwent neurodevelopment testing, and
      103 were able to undergo complete neurodevelopment testing and Bayley
      examination. Multivariate analysis controlling for socioeconomic status and
      neonatal morbidity revealed that treated hypotension is associated with delayed
      motor development and hearing loss. CONCLUSIONS: Treated hypotension in ELBW
      infants in the first 72 hours of life is associated with significant short-term
      and long-term morbidity. Infants with treated hypotension are more likely to have
      delayed motor development, hearing loss, and death.

PMID- 16585308
TI  - Lower breastfeeding rates persist among the Special Supplemental Nutrition
      Program for Women, Infants, and Children participants, 1978-2003.
AB  - OBJECTIVE: We set out to compare rates of breastfeeding between women who
      participated in the Special Supplemental Nutrition Program for Women, Infants,
      and Children (WIC) with those of non-WIC mothers from 1978 to 2003. METHODS: The
      Ross Laboratories Mothers Survey is a national survey designed to determine
      patterns of milk feeding during infancy. Mothers were asked to recall the type of
      milk fed to their infant in the hospital and during each month of age. Rates of
      breastfeeding in the hospital and at 6 months of age were evaluated. Logistic
      regression analyses identified significant predictors of breastfeeding in 2003.
      RESULTS: From 1978 through 2003, rates for the initiation of breastfeeding among
      WIC participants lagged behind those of non-WIC mothers by an average of 23.6 +/-
      4.4 percentage points. At 6 months of age, the gap between WIC participants and
      non-WIC mothers (mean: 16.3 +/- 3.1 percentage points) steadily increased from
      1978 through 2003 and exceeded 20% by 1999. Demographic factors that were
      significant and positive predictors of breastfeeding initiation in 2003 included
      some college education, living in the western region of the United States, not
      participating in the WIC program, having an infant of normal birth weight,
      primipary, and not working outside the home. For mothers of infants 6 months of
      age, WIC status was the strongest determinant of breastfeeding: mothers who were
      not enrolled in the WIC program were more than twice as likely to breastfeed at 6
      months of age than mothers who participated in the WIC program. CONCLUSIONS:
      Breastfeeding rates among WIC participants have lagged behind those of non-WIC
      mothers for the last 25 years. The Healthy People 2010 goals for breastfeeding
      will not be reached without intervention. Food package and programmatic changes
      are needed to make the incentives for breastfeeding greater for WIC participants.

PMID- 16585309
TI  - Screening for biliary atresia by infant stool color card in Taiwan.
AB  - OBJECTIVE: We aimed to detect biliary atresia (BA) in early infancy to prevent
      additional liver damage because of the delay of referral and surgical treatment
      and to investigate the incidence rate of BA in Taiwan. METHODS: A pilot study to
      screen the stool color in infants for the early diagnosis of BA was undertaken
      from March 2002 to December 2003. We had designed an "infant stool color card"
      with 7 numbers of different color pictures and attached it to the child health
      booklet. Parents were then asked to observe their infant's stool color by using
      this card. The medical staff would check the number that the parents chose
      according to their infant's stool color at 1 month of age during the health
      checkup and then send the card back to the stool color card registry center.
      RESULTS: The average return rate was approximately 65.2% (78,184 infants). A
      total of 29 infants were diagnosed as having BA, and 26 were screened out by
      stool color card before 60 days of age. The sensitivity, specificity, and
      positive predictive value were 89.7%, 99.9%, and 28.6%, respectively. Seventeen
      (58.6%) infants with BA received a Kasai operation within 60-day age period. The
      estimated incidence of BA in screened newborns was 3.7 of 10,000. CONCLUSIONS:
      The stool color card was a simple, efficient, and applicable mass screening
      method for early diagnosis and management of BA. The program can also help in
      estimating the incidence and creating a registry of these patients.

PMID- 16585310
TI  - Health-related quality of life and depressive symptoms in adolescents with
      extreme obesity presenting for bariatric surgery.
AB  - OBJECTIVE: We sought to document health-related quality of life (HRQoL)
      impairment and depressive symptomatology in adolescents with extreme obesity
      considering surgical weight loss. STUDY DESIGN: A retrospective review of
      clinical data was conducted for 33 consecutive extremely obese adolescents
      presenting for evaluation at a bariatric surgery program for adolescents.
      Adolescents completed the PedsQL and the Beck Depression Inventory. Mothers
      completed the parent-proxy PedsQL and the Child Behavior Checklist. RESULTS:
      HRQoL scores from both informants were markedly impaired relative to published
      norms on healthy youth. Moderate agreement was found for self-reported and parent
      proxy HRQoL. Approximately 30% of youth met criteria for clinically significant
      depressive symptoms when based on self-report and 45% of youth when based on
      mother report. Only 21% of youth were currently engaged in some form of
      psychological treatment (eg, medication or therapy). CONCLUSIONS: The day-to-day
      life of adolescents with extreme obesity seeking bariatric surgery is globally
      and severely impaired. However, only some of these adolescents demonstrate
      clinically significant levels of depressive symptomatology. These data will be
      critical to the development of more informed patient selection criteria and more
      efficacious treatment paradigms for this vulnerable pediatric subgroup.

PMID- 16585311
TI  - Evaluation of nonpharmacologic methods of pain and anxiety management for
      laceration repair in the pediatric emergency department.
AB  - BACKGROUND: Nonpharmacologic interventions, such as distraction, have been shown
      to be powerful adjuncts in reducing pain and anxiety in children with both acute
      and chronic painful conditions. There are no controlled studies evaluating these
      interventions as adjuncts to facilitate completion of painful procedures in the
      pediatric emergency department (ED). OBJECTIVE: We assessed the effectiveness of
      distraction techniques in reducing the sensory and affective components of pain
      among pediatric patients undergoing laceration repair in the ED. METHODS:
      Eligible children between 6 and 18 years of age (N = 240) presenting to the ED
      for laceration repair were randomly assigned to an intervention or control arm.
      Those assigned to the intervention arm were given a choice of age-appropriate
      distracters during laceration repair. Quantitative measures of pain intensity,
      situational anxiety, and pain distress (as perceived by the parent) were assessed
      by using the 7-point Facial Pain Scale, State Trait Anxiety Inventory for
      Children, and a visual analog scale, respectively, before and after laceration
      repair. The State Trait Anxiety Inventory for Children was performed in children
      > or = 10 years of age. RESULTS: There was no difference in mean change in Facial
      Pain Scale scores between the control and the intervention groups in children <
      10 years of age. Multivariate analysis in this same age group showed that the
      intervention was independently associated with a reduction in pain distress as
      perceived by parents based on the mean change in visual analog scale scores. In
      older children, the intervention was independently associated with reduction in
      situational anxiety but not in pain intensity or in parental perception of pain
      distress. CONCLUSIONS: The use of distraction techniques is effective in reducing
      situational anxiety in older children and lowering parental perception of pain
      distress in younger children. This technique may have a role in improving the
      quality of management of procedural pain in a pediatric ED setting.

PMID- 16585312
TI  - Transcutaneous bilirubin levels in the first 96 hours in a normal newborn
      population of > or = 35 weeks' gestation.
AB  - OBJECTIVE: To obtain transcutaneous bilirubin (TcB) measurements, at 6-hour
      intervals, in the first 96 hours after birth in a normal newborn population
      (gestational age: > or =35 weeks). METHODS: We performed 9397 TcB measurements on
      3984 healthy newborn infants (gestational age: > or =35 weeks) from 6 to 96 hours
      of age. All measurements were performed in the well-infant nursery with a Draeger
      Air-Shields transcutaneous jaundice meter (model JM-103), within 2 hours of the
      designated time. RESULTS: There was a distinct pattern to the velocity of the
      increase in TcB levels over different time periods. TcB levels increased in a
      linear manner most rapidly in the first 6 to 18 hours and then less rapidly from
      18 to 42 hours, followed by a much slower increase until peak levels occurred.
      Decreasing gestational age was associated significantly with higher TcB levels.
      CONCLUSIONS: We provide data on neonatal bilirubinemia, based on TcB levels
      determined in a large, predominately white and breastfed, North American
      population. Infants who require closer evaluation and observation initially are
      those whose bilirubin levels are > or =95th percentile, ie, increasing more
      rapidly than 0.22 mg/dL per hour in the first 24 hours, 0.15 mg/dL per hour
      between 24 and 48 hours, and 0.06 mg/dL per hour after 48 hours. These data
      should be useful for detecting aberrant trends, identifying infants who need
      additional evaluation, and planning appropriate follow-up for jaundiced newborns.

PMID- 16585313
TI  - Bilirubin measurement for neonates: comparison of 9 frequently used methods.
AB  - OBJECTIVE: High blood concentrations of bilirubin are toxic to the brain and may
      cause kernicterus. Therefore, determination of bilirubin levels is performed for
      many newborns, and several different methods are available. We compared 9
      frequently used methods for bilirubin determination among newborns under routine
      conditions, to define their sequence of use. METHODS: In a prospective study,
      bilirubin concentrations were determined with 9 different methods, ie, 3 skin
      test devices, 3 nonchemical photometric devices (including 2 blood gas
      analyzers), and 3 laboratory analyzers. RESULTS: A total of 124 samples were
      obtained. All 3 laboratory methods showed very strong correlations with each
      other, and their means were used as comparison values. To these comparison
      values, the skin test devices had correlation coefficients between 0.961 and
      0.966, and the nonchemical photometric devices between 0.980 and 0.994. Bland
      Altman plots demonstrated good agreement with the comparison values for all
      nonchemical photometric devices. All skin test devices and 1 nonchemical
      photometric device underestimated bilirubin levels, particularly at high
      concentrations. CONCLUSIONS: In the routine care of newborns, the first method
      for bilirubin testing should be a skin test. If the skin test result exceeds 200
      micromol/L and other analytes are to be determined with a nonchemical photometric
      device, then bilirubin can be included in this analysis and the result trusted up
      to 250 micromol/L. If the skin test result exceeds 200 micromol/L and only
      bilirubin concentrations are needed, then a standard laboratory method is the
      first choice, to avoid repeated blood sampling. Bilirubin concentrations from
      nonchemical photometric devices that exceed 250 micromol/L should be confirmed
      with standard laboratory methods.

PMID- 16585314
TI  - Satisfaction with care and ease of using health care services among parents of
      children with special health care needs: the roles of race/ethnicity, insurance,
      language, and adequacy of family-centered care.
AB  - OBJECTIVES: To examine whether racial/ethnic disparities exist in parental
      reports of satisfaction with care and ease of using health care services among
      children with special health care needs (CSHCN) and to identify factors
      associated independently with satisfaction with care and ease of use of health
      care services among CSHCN. METHODS: We analyzed data for 38,886 CSHCN <18 years
      of age in the National Survey of CSHCN, conducted from 2000 to 2002. Outcome
      variables included perceived satisfaction with care and ease of service use.
      Covariates included sociodemographic factors, insurance, interview language,
      condition severity and stability, adequacy of family-centered care measures, and
      having a personal doctor/nurse. RESULTS: The prevalences of reported
      dissatisfaction with care and problems with ease of using services among parents
      of CSHCN were 8% and 25%, respectively. Black and Hispanic parents were
      significantly more likely than white parents to be dissatisfied with care (13%
      and 16% vs 7%) and to report problems with ease of service use (35% and 34% vs
      23%). Hispanic/white disparities in satisfaction with care and ease of use of
      services disappeared only after multivariate adjustment for parental interview
      language. Black/white disparities in satisfaction with care disappeared after
      adjustments for adequacy of family-centered care measures, but black/white
      disparities in ease of using services persisted. The severity of the child's
      condition, lack of insurance, parental interview in Spanish, and inadequate
      family-centered care were associated significantly with dissatisfaction with care
      and problems with ease of using health care services. CONCLUSIONS: Policies and
      strategies that reduce language barriers, promote insurance coverage and family
      centered care, and improve ease of use of services among minority CSHCN have the
      potential to reduce racial/ethnic disparities in satisfaction with care and to
      promote ease of use of services among families with CSHCN.

PMID- 16585315
TI  - Tipping the scales: obese children and child safety seats.
AB  - OBJECTIVE: To shed light on the extent to which childhood obesity affects the
      types of appropriate child safety seats for young children, by providing an
      estimate of the number of US children whose weight renders them unable to use
      safely the majority of child safety seat types currently available. METHODS: The
      types of appropriate child safety seats were assessed by using National Highway
      Traffic Safety Administration 2005 Child Safety Seat Ease of Use Ratings.
      Estimates of the numbers of children weighing above the maximal weight for those
      child safety seats were calculated by using the tabulations of growth curves
      based on National Health and Nutrition Examination Survey 1999 to 2000 data that
      were assembled by the National Center for Health Statistics and the US Census for
      the year 2000. RESULTS: A total of 283,305 children 1 to 6 years of age would
      have a difficult (if not impossible) time finding a safe child safety seat
      because of their age and weight. The vast majority of these children are 3 years
      of age and weigh >40 lb (182,661 children). For these children, there are
      currently only 4 child safety seat types available, each of which costs between
      $240 and $270. CONCLUSIONS: This study determined that there is limited
      availability of child safety seat types for the ever-increasing number of obese
      young children. There are substantial numbers of children who weigh more than the
      upper weight limit for most currently available child safety seats. While we
      await reductions in the childhood obesity epidemic, options for maximizing the
      protection of obese children in automobiles must be identified.

PMID- 16585316
TI  - A prospective study of psychological predictors of body fat gain among children
      at high risk for adult obesity.
AB  - OBJECTIVE: Limited data suggest that psychological factors, including binge
      eating, dieting, and depressive symptoms, may predispose children to excessive
      weight gain. We investigated the relationship between baseline psychological
      measures and changes in body fat (measured with dual-energy x-ray absorptiometry)
      over time among children thought to be at high risk for adult obesity. METHODS: A
      cohort study of a convenience sample of children (age: 6-12 years) recruited from
      Washington, DC, and its suburbs was performed. Subjects were selected to be at
      increased risk for adult obesity, either because they were overweight when first
      examined or because their parents were overweight. Children completed
      questionnaires at baseline that assessed dieting, binge eating, disordered eating
      attitudes, and depressive symptoms; they underwent measurements of body fat mass
      at baseline and annually for an average of 4.2 years (SD: 1.8 years). RESULTS:
      Five hundred sixty-eight measurements were obtained between July 1996 and
      December 2004, for 146 children. Both binge eating and dieting predicted
      increases in body fat. Neither depressive symptoms nor disturbed eating attitudes
      served as significant predictors. Children who reported binge eating gained, on
      average, 15% more fat mass, compared with children who did not report binge
      eating. CONCLUSIONS: Children's reports of binge eating and dieting were salient
      predictors of gains in fat mass during middle childhood among children at high
      risk for adult obesity. Interventions targeting disordered eating behaviors may
      be useful in preventing excessive fat gain in this high-risk group.

PMID- 16585317
TI  - Complications of central venous catheters used for the treatment of acute
      hematogenous osteomyelitis.
AB  - OBJECTIVE: To determine the complications and risk factors for complications
      associated with using central venous catheters (CVCs) for the treatment of acute
      hematogenous osteomyelitis (AHO). METHODS: We conducted a retrospective cohort
      study of all patients admitted to the Children's Hospital of Philadelphia between
      January 1, 2000, and December 31, 2003, with a diagnosis of AHO. RESULTS: Eighty
      patients with AHO met inclusion criteria. The median age was 5 years, and 66% of
      the patients were male. The most commonly affected bones were the femur (25%),
      tibia (20%), and pelvis (16%). Staphylococcus aureus was the most common organism
      identified from cultures of bone (67%) and blood (30%). Seventy-five patients
      (94%) received >2 weeks of intravenous (IV) antibiotic therapy via a CVC and 5
      (6%) received <2 weeks of IV antibiotic therapy before conversion to oral therapy
      for a median of 25 days. None of the patients who switched to oral therapy within
      2 weeks was rehospitalized or returned to the emergency department. Of the 75
      patients who received >2 weeks of IV therapy, 41% had > or =1 CVC-associated
      complication. Seventeen patients (23%) had a CVC malfunction or displacement, 8
      (11%) had a catheter-associated bloodstream infection, 8 (11%) had fever with
      negative blood culture results, and 4 (5%) had a local skin infection at the site
      of catheter insertion. Older age was protective against the development of a CVC
      associated complication, whereas the lowest median household income was
      associated with development of a CVC-associated complication. CONCLUSIONS:
      Interventions to reduce CVC-associated complications should be developed and
      evaluated, particularly for young children and those from families with low
      household incomes. Clinical trials are needed to evaluate the safety and efficacy
      of oral antibiotic therapy after a short course of IV therapy as an alternative
      to prolonged IV therapy.

PMID- 16585318
TI  - How do psychological factors influence adolescent smoking progression? The
      evidence for indirect effects through tobacco advertising receptivity.
AB  - OBJECTIVES: To determine whether novelty seeking and depressive symptoms had
      mediated or indirect effects on adolescent smoking progression through tobacco
      advertising receptivity. METHODS: More than 1000 adolescents were monitored from
      9th grade to 12th grade and completed annual surveys that measured demographic
      characteristics, smoking behavior, tobacco advertising receptivity, novelty
      seeking personality, depressive symptoms, family and peer smoking, alcohol use,
      and marijuana use. RESULTS: Latent growth modeling indicated that novelty seeking
      had a significant indirect effect on smoking progression through baseline tobacco
      advertising receptivity. For each 1-SD increase in novelty seeking, the odds of
      being more receptive to tobacco advertising increased by 12% (ie, being in a
      specific category or higher), which in turn resulted in an 11% increase in the
      odds of smoking progression from 9th grade to 12th grade. The indirect effect
      from depressive symptoms to smoking progression did not reach significance.
      CONCLUSIONS: These findings may inform future research on other factors that
      influence tobacco advertising receptivity, as well as programs aimed at
      preventing adolescent smoking initiation and progression.

PMID- 16585319
TI  - High concentrations of plasminogen activator inhibitor-1 in lungs of preterm
      infants with respiratory distress syndrome.
AB  - BACKGROUND: Among preterm infants, respiratory distress syndrome (RDS) is
      characterized by the presence of intraalveolar fibrin deposition. Fibrin monomers
      inhibit surfactant function effectively. However, little is known about potential
      disturbances of intraalveolar fibrinolysis in RDS. We studied levels of major
      plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator
      (tPA), and urokinase-type plasminogen activator (uPA) in lungs of preterm infants
      with RDS. METHODS: The antigen levels of PAI-1, tPA, and uPA were measured in 262
      samples of tracheal aspirate fluid collected from 37 intubated preterm infants
      during the first 2 postnatal weeks. To examine the expression of PAI-1, tPA, and
      uPA in lung tissue, immunohistochemical analyses were performed on autopsy
      specimens from 7 preterm infants with RDS and 6 newborn infants without pulmonary
      pathologic conditions. RESULTS: For infants with an immature surfactant profile,
      as indicated by lecithin/sphingomyelin ratios in tracheal aspirate fluid of < 10,
      PAI-1 levels and ratios of PAI-1 to uPA and tPA were significantly higher during
      postnatal days 1 to 2, compared with infants with lecithin/sphingomyelin ratios
      of > or = 10. Moreover, infants who subsequently developed bronchopulmonary
      dysplasia (BPD) (n = 15) had higher PAI-1 levels on days 3 to 4 and days 7 to 8
      than did those who survived without BPD. For preterm infants with RDS,
      immunohistochemical analyses demonstrated increased expression of PAI-1, tPA, and
      uPA predominantly in alveolar epithelium. CONCLUSIONS: High concentrations of PAI
      1 and an increased ratio of PAI-1 to uPA, with a concurrently less-increased
      ratio of PAI-1 to tPA, are associated with the severity of RDS among preterm
      infants during the first postnatal days. Pulmonary inhibition of fibrinolysis is
      a pathophysiologic feature of RDS and may play a role in the development of BPD.

PMID- 16585320
TI  - Delayed cord clamping in very preterm infants reduces the incidence of
      intraventricular hemorrhage and late-onset sepsis: a randomized, controlled
      trial.
AB  - OBJECTIVE: This study compared the effects of immediate (ICC) and delayed (DCC)
      cord clamping on very low birth weight (VLBW) infants on 2 primary variables:
      bronchopulmonary dysplasia (BPD) and suspected necrotizing enterocolitis (SNEC).
      Other outcome variables were late-onset sepsis (LOS) and intraventricular
      hemorrhage (IVH). STUDY DESIGN: This was a randomized, controlled unmasked trial
      in which women in labor with singleton fetuses <32 weeks' gestation were randomly
      assigned to ICC (cord clamped at 5-10 seconds) or DCC (30-45 seconds) groups.
      Women were excluded for the following reasons: their obstetrician refused to
      participate, major congenital anomalies, multiple gestations, intent to withhold
      care, severe maternal illnesses, placenta abruption or previa, or rapid delivery
      after admission. RESULTS: Seventy-two mother/infant pairs were randomized.
      Infants in the ICC and DCC groups weighed 1151 and 1175 g, and mean gestational
      ages were 28.2 and 28.3 weeks, respectively. Analyses revealed no difference in
      maternal and infant demographic, clinical, and safety variables. There were no
      differences in the incidence of our primary outcomes (BPD and suspected NEC).
      However, significant differences were found between the ICC and DCC groups in the
      rates of IVH and LOS. Two of the 23 male infants in the DCC group had IVH versus
      8 of the 19 in the ICC group. No cases of sepsis occurred in the 23 boys in the
      DCC group, whereas 6 of the 19 boys in the ICC group had confirmed sepsis. There
      was a trend toward higher initial hematocrit in the infants in the DCC group.
      CONCLUSIONS: Delayed cord clamping seems to protect VLBW infants from IVH and
      LOS, especially for male infants.

PMID- 16585321
TI  - Targeted short-term fluconazole prophylaxis among very low birth weight and
      extremely low birth weight infants.
AB  - OBJECTIVES: To assess whether targeted short-term fluconazole prophylaxis reduces
      late-onset (>3 days of age) invasive fungal infection (IFI) among very low birth
      weight infants and extremely low birth weight (ELBW) infants and to assess
      mortality rates, toxicity, and costs associated with this intervention. METHODS:
      An observational study of 2 subsequent epochs of inborn infants with birth weight
      of <1500 g or gestational age of <32 weeks, 1 before (control) and 1 after
      (fluconazole) initiation of routine targeted fluconazole prophylaxis in March
      2003, was performed. Targeted fluconazole (3 mg/kg) prophylaxis was administered
      to infants for whom a decision was made to administer broad-spectrum antibiotics
      for >3 days. RESULTS: IFI was observed for 13 (6.3%) of 206 infants in the
      control epoch and 2 (1.1%) of 178 in the fluconazole epoch, with a common odds
      ratio of 0.166. Logistic regression analysis taking into account all published
      factors (except for fungal colonization) showed that the fluconazole epoch was
      associated significantly with lower IFI rates. We observed no change in late (>3
      days) mortality rates (11 of 206 infants in the control epoch vs 8 of 178 infants
      in the prophylaxis epoch). The mortality rate for ELBW infants with IFI was low
      (15%) in our study. Fluconazole was administered to 81% of ELBW infants, who
      received a median of 8 doses, and 41% of larger infants, who received a median of
      5 doses. The intervention was cost-effective, and the effective number needed to
      treat to prevent 1 IFI was 10. CONCLUSIONS: This study suggests that targeted
      short-course fluconazole prophylaxis in very low birth weight and ELBW infants
      may be efficacious and cost effective.

PMID- 16585322
TI  - Growth in the neonatal intensive care unit influences neurodevelopmental and
      growth outcomes of extremely low birth weight infants.
AB  - OBJECTIVES: The objectives of this study were to assess whether (1) in-hospital
      growth velocity is predictive of neurodevelopmental and growth outcomes at 18 to
      22 months' corrected age among extremely low birth weight (ELBW) infants and (2)
      in-hospital growth velocity contributes to these outcomes after controlling for
      confounding demographic and clinical variables. METHODS: Infants 501 to 1000 g
      birth weight from a multicenter cohort study were divided into quartiles of in
      hospital growth velocity rates. Variables considered for the logistic-regression
      models included gender, race, gestational age, small for gestational age,
      mother's education, severe intraventricular hemorrhage, periventricular
      leukomalacia, age at regaining birth weight, necrotizing enterocolitis, late
      onset infection, bronchopulmonary dysplasia, postnatal steroid therapy for
      pulmonary disease, and center. RESULTS: Of the 600 discharged infants, 495 (83%)
      were evaluated at 18 to 22 months' corrected age. As the rate of weight gain
      increased between quartile 1 and quartile 4, from 12.0 to 21.2 g/kg per day, the
      incidence of cerebral palsy, Bayley II Mental Developmental Index (MDI) <70 and
      Psychomotor Developmental Index (PDI) <70, abnormal neurologic examination,
      neurodevelopmental impairment, and need for rehospitalization fell significantly.
      Similar findings were observed as the rate of head circumference growth
      increased. The in-hospital rate of growth was associated with the likelihood of
      anthropometric measurements at 18 months' corrected age below the 10th percentile
      values of the Centers for Disease Control and Prevention 2000 growth curve.
      Logistic-regression analyses, controlling for potential demographic or clinical
      cofounders, and adjusted for center, identified a significant relationship
      between growth velocity and the likelihood of cerebral palsy, MDI and PDI scores
      of <70, and neurodevelopmental impairment. CONCLUSIONS: These analyses suggest
      that growth velocity during an ELBW infant's NICU hospitalization exerts a
      significant, and possibly independent, effect on neurodevelopmental and growth
      outcomes at 18 to 22 months' corrected age.

PMID- 16585323
TI  - How does maternal and child feeding behavior relate to weight gain and failure to
      thrive? Data from a prospective birth cohort.
AB  - OBJECTIVES: The aim of this study was to study the influences of child and
      maternal feeding behavior on weight gain and failure to thrive in the first year
      of life. METHODS: The Millennium Infant Study recruited a population birth cohort
      in Northeast England shortly after birth and studied them prospectively to the
      age of 13 months. Parents completed questionnaires at 6 weeks and 4, 8, and 12
      months. Appetite was rated on a 5-point scale at each age, and a core group of
      questions was used to generate scores of oromotor dysfunction, avoidant eating
      behavior, maternal feeding anxiety, and response to food refusal. Routinely
      collected weights were used to assess weight gain using the thrive index (TI);
      weight faltering was defined as TI below the 5th percentile from birth to age 6
      weeks or 4, 8, or 12 months. RESULTS: Of 923 eligible infants, 75% of the mothers
      returned at least 1 questionnaire and > or =2 weights. Weight gain to 6 weeks was
      independently related to appetite and oromotor dysfunction rated at 6 weeks.
      Appetite rated at 6 weeks and 12 months both independently predicted weight gain
      to 12 months. Some avoidant eating behavior was seen in most children by 12
      months old, but there was no relationship with weight gain or faltering after
      adjustment for appetite. However, the extent to which caregivers responded to
      food refusal was a significant inverse predictor of weight gain, even after
      adjustment for appetite. CONCLUSIONS: Inherent child appetite characteristics
      seem to be an important risk factor for weight faltering and failure to thrive,
      but high maternal promotion of feeding may also have an adverse influence.

PMID- 16585324
TI  - The current etiologic profile and neurodevelopmental outcome of seizures in term
      newborn infants.
AB  - OBJECTIVES: The objectives of this study were to delineate the etiologic profile
      and neurodevelopmental outcome of neonatal seizures in the current era of
      neonatal intensive care and to identify predictors of neurodevelopmental outcome
      in survivors. METHODS: Eighty-nine term infants with clinical neonatal seizures
      underwent neurologic examination, electroencephalography (EEG), neuroimaging, and
      extensive diagnostic tests in the newborn period. After discharge, all infants
      underwent regular neurologic evaluations and, at 12 to 18 months, formal
      neurodevelopmental testing. We tested the prognostic value of seizure etiology,
      neurologic examination, EEG, and neuroimaging. RESULTS: Etiology was found in 77
      infants. Global cerebral hypoxia-ischemia, focal cerebral hypoxia-ischemia, and
      intracranial hemorrhage were most common. Neonatal mortality was 7%; 28% of the
      survivors had poor long-term outcome. Association between seizure etiology and
      outcome was strong, with cerebral dysgenesis and global hypoxia-ischemia
      associated with poor outcome. Normal neonatal period/early infancy neurologic
      examination was associated with uniformly favorable outcome at 12 to 18 months;
      abnormal examination lacked specificity. Normal/mildly abnormal neonatal EEG had
      favorable outcome, particularly if neonatal neuroimaging was normal.
      Moderate/severely abnormal EEG, and multifocal/diffuse cortical or primarily deep
      gray matter lesions, had a worse outcome. CONCLUSIONS: Mortality associated with
      neonatal seizures has declined although long-term neurodevelopmental morbidity
      remains unchanged. Seizure etiology and background EEG patterns remain powerful
      prognostic factors. Diagnostic advances have changed the etiologic distribution
      for neonatal seizures and improved accuracy of outcome prediction. Global
      cerebral hypoxia-ischemia, the most common etiology, is responsible for the large
      majority of infants with poor long-term outcome.

PMID- 16585325
TI  - Physical activity and sedentary behavior patterns are associated with selected
      adolescent health risk behaviors.
AB  - OBJECTIVE: Little is known about how physical activity (PA), sedentary behavior,
      and various adolescent health risk behaviors are associated. The objective of
      this study was to examine relationships between PA and sedentary behavior
      patterns and an array of risk behaviors, including leading causes of adolescent
      morbidity/mortality. METHODS: Nationally representative self-reported data were
      collected (National Longitudinal Study of Adolescent Health; wave I: 1994-1995;
      II: 1996; N = 11957). Previously developed and validated cluster analyses
      identified 7 homogeneous groups of adolescents sharing PA and sedentary
      behaviors. Poisson regression predicted the relative risk of health risk
      behaviors, other weekly activities, and self-esteem across the 7 PA/sedentary
      behavior clusters controlling for demographics and socioeconomic status. Main
      outcome measures were adolescent risk behaviors (eg, truancy, cigarette smoking,
      sexual intercourse, delinquency), other weekly activities (eg, work, academic
      performance, sleep), self-esteem. RESULTS: Relative to high television (TV) and
      video viewers, adolescents in clusters characterized by skating and video gaming,
      high overall sports and sports participation with parents, using neighborhood
      recreation center, strict parental control of TV, reporting few activities
      overall, and being active in school were less likely to participate in a range of
      risky behaviors, ranging from an adjusted risk ratio (ARR) of 0.42 (outcome:
      illegal drug use, cluster: strict parental control of TV) to 0.88 (outcome:
      violence, cluster: sports with parents). Active teens were less likely to have
      low self-esteem (eg, adolescents engaging in sports with parents, ARR: 0.73) and
      more likely to have higher grades (eg, active in school, ARR: 1.20). CONCLUSIONS:
      Participation in a range of PA-related behaviors, particularly those
      characterized by high parental sports/exercise involvement, was associated with
      favorable adolescent risk profiles. Adolescents with high TV/video viewership
      were less likely to have positive risk behavior outcomes. Enhancing opportunities
      for PA and sport may have a beneficial effect on leading adolescent risk
      behaviors.

PMID- 16585326
TI  - Longitudinal follow-up of families and young children with traumatic brain
      injury.
AB  - OBJECTIVES: To examine the stability of functional outcomes 2 years after injury
      among children who sustained a traumatic brain injury (TBI) before 2 years of age
      and to examine the characteristics of the families caring for these children.
      METHODS: All North Carolina-resident children who were hospitalized between
      January 2000 and December 2001 in any of the state's 9 PICUs and survived a TBI
      that occurred on or before their second birthday were eligible to participate in
      the prospective cohort study. Child health status, use of ancillary medical
      resources, and family characteristics were assessed through maternal caregiver
      interviews approximately 2 years after injury. Comparisons were made among injury
      types (inflicted versus noninflicted). RESULTS: There were 112 children who
      survived a TBI during the 2-year study period. Fifty-seven (79%) of the 72
      maternal caregivers who had completed an interview 1 year after the child's
      injury participated in the year 2 interview. Most children (67%) had an outcome
      of mild disability or better at year 2, with 45% functioning at an age
      appropriate level. Children's outcomes did not differ significantly at year 2
      according to the mechanism of injury. The majority (67%) of children retained
      their Pediatric Overall Performance Category scores from year 1 to year 2.
      Children who changed were as likely to show improvement as deterioration.
      Children differed very little across time, as measured with the Stein-Jessup
      Functional Status II (Revised) scale. Families tended to have multiple
      environmental factors that could put their children at risk for poor
      developmental outcomes, including living below the poverty level (22%) and low
      social capital (39%). CONCLUSIONS: The children in this cohort had relatively
      stable functional outcomes from year 1 to year 2 after injury. This population of
      children remains very vulnerable to poor developmental outcomes secondary to the
      effects of their TBI and environmental factors.

PMID- 16585327
TI  - Relation of pregnancy and neonatal factors to subsequent development of childhood
      epilepsy: a population-based cohort study.
AB  - OBJECTIVE: We examined the effect of pregnancy and neonatal factors on the
      subsequent development of childhood epilepsy in a population-based cohort study.
      PATIENTS AND METHODS: Children born between January 1986 and December 2000 in
      Nova Scotia, Canada were followed up to December 2001. Data on pregnancy and
      neonatal events and on diagnoses of childhood epilepsy were obtained through
      record linkage of 2 population-based databases: the Nova Scotia Atlee Perinatal
      Database and the Canadian Epilepsy Database and Registry. Factors analyzed
      included events during the prenatal, labor and delivery, and neonatal time
      periods. Cox proportional hazards regression models were used to estimate
      relative risks and 95% confidence intervals. RESULTS: There were 648 new cases of
      epilepsy diagnosed among 124,207 live births, for an overall rate of 63 per
      100,000 person-years. Incidence rates were highest among children <1 year of age.
      In adjusted analyses, factors significantly associated with an increased risk of
      epilepsy included eclampsia, neonatal seizures, central nervous system (CNS)
      anomalies, placental abruption, major non-CNS anomalies, neonatal metabolic
      disorders, neonatal CNS diseases, previous low birth weight infant, infection in
      pregnancy, small for gestational age, unmarried, and not breastfeeding infant at
      the time of discharge from hospital. CONCLUSIONS: Our study supports the concept
      that prenatal factors contribute to the occurrence of subsequent childhood
      epilepsy.

PMID- 16585328
TI  - In-hospital mortality for children with hypoplastic left heart syndrome after
      stage I surgical palliation: teaching versus nonteaching hospitals.
AB  - OBJECTIVES: Teaching hospitals are perceived to provide a higher quality of care
      for the treatment of rare disease and complex patients. A substantial proportion
      of stage I palliation for hypoplastic left heart syndrome (HLHS) may be performed
      in nonteaching hospitals. This study compares the in-hospital mortality of stage
      I palliation between teaching and nonteaching hospitals. METHODS: The authors
      conducted a retrospective cohort study using the Kids' Inpatient Database 1997
      and 2000. Patients with HLHS undergoing stage I palliation were identified using
      International Classification of Diseases, Ninth Revision, Clinical Modification
      diagnostic and procedural codes. RESULTS: Seven hundred fifty-four and 880
      discharges of children with HLHS undergoing stage I palliation in 1997 and 2000,
      respectively, were identified. The in-hospital mortality for the study population
      was 28% in 1997 and 24% in 2000. Twenty percent of stage I palliation operations
      were performed in nonteaching hospitals in 1997. Two percent of operations were
      performed in nonteaching hospitals in 2000. In 1997 only, in-hospital mortality
      remained higher in nonteaching hospitals after controlling for stage I palliation
      hospital volume and condition-severity diagnoses. Low-volume hospitals performing
      stage I palliation were associated with increased in-hospital mortality in 1997
      and 2000. CONCLUSIONS: Patients with HLHS undergoing stage I palliation in
      nonteaching hospitals experienced increased in-hospital mortality in 1997. A
      significant reduction in the number of stage I palliation procedures performed in
      nonteaching hospitals occurred between 1997 and 2000. This centralization of
      stage I palliation into teaching hospitals, along with advances in postoperative
      medical and surgical care for these children, was associated with a decrease in
      mortality. Patients in low-volume hospitals performing stage I palliation
      continued to experience increased mortality in 2000.

PMID- 16585329
TI  - Symptoms affecting children with malignancies during the last month of life: a
      nationwide follow-up.
AB  - OBJECTIVE: In a population-based nationwide survey, we aimed to study symptoms in
      children with malignancies during the last month of their lives. Understanding
      which symptoms affect children in the terminal phase of disease is crucial to
      improve palliative care. METHODS: We attempted to contact all parents in Sweden
      who had lost a child to cancer during a 6-year period. The parents were asked,
      through an anonymous postal questionnaire, about symptoms that affected the
      child's sense of well-being during the last month of life. RESULTS: Information
      was supplied by 449 (80%) of 561 eligible parents. The symptoms most frequently
      reported with high or moderate impact on the child's well-being were: physical
      fatigue (86%), reduced mobility (76%), pain (73%), and decreased appetite (71%).
      Irrespective of the specific malignancy, physical fatigue was the most frequently
      reported symptom, and pain was among the 3 most frequently reported. Children who
      died at 9 to 15 years of age were reported to be moderately or severely affected,
      by a number of symptoms, significantly more often than other children. The gender
      of the reporting parent had no significant bearing on any of the symptoms
      reported. CONCLUSIONS: The most frequently reported symptoms in children with
      malignancies to be aware of and possibly address during the terminal phase are
      physical fatigue, reduced mobility, pain, and decreased appetite. Children aged 9
      to 15 years are reported to be moderately or severely affected by more symptoms
      than children in other age groups. Mothers and fathers report a similar
      prevalence of symptoms.

PMID- 16585330
TI  - Cumulative social disadvantage and child health.
AB  - CONTEXT: Disparities in child health are a major public health concern. However,
      it is unclear whether these are predominantly the result of low income, race, or
      other social risk factors that may contribute to their health disadvantage.
      Although others have examined the effects of the accumulation of risk factors,
      this methodology has not been applied to child health. OBJECTIVE: We tested 4
      social risk factors (poverty, minority race/ethnicity, low parental education,
      and not living with both biological parents) to assess whether they have
      cumulative effects on child health and examined whether access to health care
      reduced health disparities. DESIGN: We analyzed data on 57,553 children <18 years
      from the 1994 and 1995 National Health Interview Survey Disability Supplement. Of
      the 4 risk factors, 3 (poverty, low parental education, and single-parent
      household) were consistently associated with child health. These were summed,
      generating the Social Disadvantage Index (range: 0-3). RESULTS: A total of 43.6%
      of children had no social disadvantages, 30.8% had 1, 15.6% had 2, and 10.0% had
      all 3. Compared with those with no social disadvantages, the odds ratios (ORs) of
      being in "good, fair, or poor health" (versus "excellent or very good") were 1.95
      for 1 risk, 3.22 for 2 risks, and 4.06 for 3 risks. ORs of having a chronic
      condition increased from 1.25 (1 risk) to 1.60 (2 risks) to 2.11 (3 risks). ORs
      for activity limitation were 1.51 (1 risk) to 2.14 (2 risks) and 2.88 (3 risks).
      Controlling for health insurance did not affect these findings. CONCLUSIONS: The
      accumulation of social disadvantage among children was strongly associated with
      poorer child health and having insurance did not reduce the observed health
      disparities.

PMID- 16585331
TI  - Do parenting and the home environment, maternal depression, neighborhood, and
      chronic poverty affect child behavioral problems differently in different racial
      ethnic groups?
AB  - OBJECTIVE: To determine whether the processes through which parenting practices,
      maternal depression, neighborhood, and chronic poverty affect child behavioral
      problems are similar or different in minority and nonminority children in the
      United States. METHODS: Data from 884 white, 538 black, and 404 Latino families
      with children who were 6 to 9 years of age in the National Longitudinal Survey of
      Youth were analyzed. The outcome, child behavioral problems, was measured using
      the Behavior Problems Index externalizing and internalizing subscales. The
      effects of chronic poverty, neighborhood, maternal depression, and parenting on
      the outcome were analyzed using multigroup structural equation modeling. RESULTS:
      Chronic poverty affected child behavioral problems indirectly through the other
      variables, and parenting practices had direct effects in each racial/ethnic
      group. The effects of maternal depression were partially mediated through
      parenting in the white and Latino samples but were direct and unmediated through
      parenting practices in the black sample. Neighborhood effects were present in the
      white and black samples but were not significant for the Latino sample.
      CONCLUSIONS: Chronic poverty, neighborhood, maternal depression, and parenting
      practices have effects on child behavioral problems in white, black, and Latino
      children, but the processes and mechanisms through which they exert their effects
      differ among the groups. The differences may be related to social stratification
      mechanisms as well as sociocultural differences in family and childrearing
      practices.

PMID- 16585332
TI  - Cigarette smoking in the adolescent children of drug-abusing fathers.
AB  - OBJECTIVE: This study examined the longitudinal predictors of cigarette smoking
      in a sample of at-risk adolescents whose fathers were drug abusers (N = 296).
      METHODS: At time 1, structured interviews were administered, separately and in
      private, to male and female youth (X age = 16.3) and their fathers; adolescents
      were reinterviewed approximately 1 year later (at time 2). Structural equation
      modeling was used to examine the interrelationship of time 1 paternal tobacco and
      illicit drug use, father-child relations, adolescent psychological adjustment,
      and peer group factors and adolescent smoking at time 2. A supplementary analysis
      assessed the same model with control on the adolescent's age, gender, frequency
      of contact with the father, and the father's treatment status. RESULTS: The
      structural equation model showed a mediational pathway linking paternal tobacco
      and drug use to a weak and conflictual father-child relationship, which was
      associated with greater adolescent maladjustment, which in turn was related to
      deviant peer affiliations, which predicted adolescent smoking at time 2. There
      was also a direct path from paternal tobacco and drug use to adolescent time 2
      smoking. The supplementary analysis found no significant differences between the
      models with and without control. CONCLUSIONS: Findings provide evidence of the
      mechanisms that underlie the association between paternal drug use
      characteristics and smoking in the adolescent child. Clinical implications
      suggest the importance of the father-child relationship to smoking prevention
      programs for at-risk youth.

PMID- 16585333
TI  - Prevalence and correlates of depressed mood among youth with diabetes: the SEARCH
      for Diabetes in Youth study.
AB  - OBJECTIVE: The objective of this study was to determine if depressed mood among
      youth with diabetes was associated with type and duration of diabetes, mean
      glycosylated hemoglobin (HbA1c) level, and the frequency of diabetic ketoacidosis
      (DKA) and hypoglycemic episodes, hospitalizations, and emergency department (ED)
      visits. METHODS: A total of 2672 youth (aged 10-21 years) who had diabetes for a
      mean duration of 5 years completed a SEARCH study visit, in which their HbA1c was
      measured and information about their demographic characteristics, diabetes type
      and duration, and episodes of DKA, hypoglycemia, hospitalizations, and ED visits
      over the previous 6 months was collected. Their level of depressed mood was
      measured using the Center for Epidemiologic Studies Depression Scale (CES-D).
      RESULTS: Among these youth, 14% had mildly (CES-D 16-23) and 8.6% had moderately
      or severely (CES-D > or =24) depressed mood. Females had a higher mean CES-D
      score than males. After adjusting for demographic factors, and duration of
      diabetes, we found the prevalence of depressed mood to be higher among males with
      type 2 diabetes than those with type 1 diabetes and to be higher among females
      with comorbidities than those without comorbidities. Higher mean HbA1c and
      frequency of ED visits were associated with depressed mood. The prevalence of
      depressed mood among youth with diabetes was similar to that of published
      estimates of depressed mood among youth without diabetes. CONCLUSIONS: Physicians
      and other health care professionals should consider screening youth with diabetes
      for depressed mood in clinical settings, particularly youth with poor glycemic
      control, those with a history of frequent ED visits, males with type 2 diabetes,
      and females with comorbidities.

PMID- 16585334
TI  - Pediatric sport-related concussion: a review of the clinical management of an oft
      neglected population.
AB  - Athletic concussion is a growing focus of attention for pediatricians. Although
      numerous literature reviews and clinical guidelines are now available pertaining
      to athletic concussion, few have focused on the pediatric athlete in particular.
      Sport-related concussions occur relatively frequently in children and
      adolescents, and primary health care providers are often responsible for
      coordinating clinical management. Here we summarize the scientific literature
      pertinent to the care of young athletes. We examine how concussion affects
      younger and older athletes differently at biomechanical, pathophysiological,
      neurobehavioral, and contextual levels. We also discuss important issues in
      clinical management, including preparticipation assessment, concussion evaluation
      and recovery tracking, and when and how to return pediatric athletes to play
      sports. We also briefly cover non-sport-related interventions (eg, school
      support). With proper management, most children and adolescents sustaining a
      sport-related concussion can be expected to recover fully.

PMID- 16585335
TI  - The role of functional neuroimaging in pediatric brain injury.
AB  - The aim of this article is to review empirical studies published in the last 10
      years that used various functional neuroimaging techniques to assess pediatric
      patients with brain injury. Overall, these studies have demonstrated the ability
      of functional neuroimaging to offer unique information concerning the diagnosis,
      clinical outcome, and recovery mechanisms after pediatric brain injury. Future
      research using functional neuroimaging is recommended to better understand the
      functional reorganization and neurodevelopmental consequences resulting from
      brain injury. Such research might allow clinicians to design tailored early
      intervention and rehabilitation programs to maximize the recovery process for
      pediatric patients. Limitations and advantages associated with the use of
      functional neuroimaging in pediatric populations are discussed.

PMID- 16585336
TI  - Do differences in the American Academy of Pediatrics and the American College of
      Obstetricians and Gynecologists positions on the ethics of maternal-fetal
      interventions reflect subtly divergent professional sensitivities to pregnant
      women and fetuses?
AB  - As therapeutic interventions that are designed for the direct benefit of the
      fetus have evolved, pediatric specialists along with obstetricians have become
      increasingly engaged in the management of pregnancies that are complicated by
      fetal disorders. Do the 2 groups of medical specialists hold differing "world
      views" on the nature of the maternal-fetal relationship that could have an impact
      on decision-making? A direct comparison of the positions of the ethics committees
      of the American Academy of Pediatrics and the American College of Obstetricians
      and Gynecologists concerning maternal-fetal conflicts and fetal therapy reveals
      subtle but telling differences. Compared with the American College of
      Obstetricians and Gynecologists policy, the American Academy of Pediatrics
      statement accords somewhat less weight to maternal decision-making and is more
      tolerant of overriding maternal refusal of interventions that are recommended for
      fetal benefit. In doing so, it may oblige pregnant patients to assume greater
      risk and tolerate diminished autonomy. We urge leaders from both disciplines to
      meet and seek consensus so that a common approach and language can guide
      treatment of the patients whom we share.

PMID- 16585337
TI  - Perspectives on the pediatric HIV/AIDS pandemic: catalyzing access of children to
      care and treatment.
AB  - The successes of the United States and other developed countries in the
      prevention and treatment of pediatric HIV/AIDS have not been replicated in the
      developing world, where children continue to become infected with HIV and die
      from HIV/AIDS at astounding rates. Children are underrepresented among recipients
      of antiretroviral therapy in almost every setting worldwide where treatment
      programs have been established. The barriers to scaling up HIV/AIDS care and
      treatment globally are substantial. Nevertheless, nearly a decade after the
      introduction of pediatric highly active antiretroviral therapy in the United
      States, the opportunity finally exists to provide treatment to huge numbers of
      HIV-infected children in the developing world, changing forever the way that
      pediatric HIV/AIDS is perceived and managed. We propose the creation of a
      Clinical Centers of Excellence Network and Pediatric AIDS Corps of US pediatric
      health professionals, increased support for pediatric research relevant to
      resource-poor settings, commitment of the US government and others to
      proportionate funding for pediatric HIV/AIDS care and treatment, expanded
      availability of pediatric antiretroviral drug formulations, and a renewed
      commitment to collaborative partnerships as practical steps that can be taken to
      dramatically expand access of HIV-infected children and families in the
      developing world to health-restoring, life-prolonging care and treatment.

PMID- 16585338
TI  - Prevalence of neural tube defects, folate status, and folate fortification of
      enriched cereal-grain products in the United States.

PMID- 16585339
TI  - The folate debate.

PMID- 16585340
TI  - Weighing the risks of consumer-driven health plans for families.

PMID- 16585341
TI  - An innovative model of home-based neonatal care and research in India.

PMID- 16585342
TI  - "Clueless": why do pediatricians underestimate the media's influence on children
      and adolescents?

PMID- 16585343
TI  - Lower breastfeeding rates among supplemental nutrition program for women,
      infants, and children participants: a call for action.

PMID- 16585344
TI  - Delayed cord clamping in preterm infants.

PMID- 16585345
TI  - Investigating diagnostic substitution and autism prevalence trends.

PMID- 16585346
TI  - Diagnostic substitution and changing autism prevalence.

PMID- 16585347
TI  - Lung lesions in children with Crohn's disease presenting as nonresolving
      pneumonias and response to infliximab therapy.
AB  - Lung lesions in children with Crohn's disease are often difficult to diagnose and
      treat. We report here 3 children (aged 13, 14, and 17 years) on immunosuppressive
      therapy for previously diagnosed Crohn's disease who presented with nonresolving
      pneumonias. All 3 had unfavorable response to empiric antibiotics and had
      progression of lesions. Cultures of sputum and blood did not yield any organisms.
      Subsequent lung biopsies revealed noncaseating granulomas with giant cells in 2
      subjects and bronchiolitis obliterans with organizing pneumonia in the third. All
      patients were treated with infliximab, a novel anti-tumor necrosis factor
      monoclonal antibody, and showed rapid clinical and radiologic response. We
      emphasize that a high index of suspicion for noninfectious etiologies needs to be
      maintained in patients with Crohn's disease who present with lung lesions to
      ensure timely intervention. Infliximab therapy seems to be effective and well
      tolerated in such patients.

PMID- 16585348
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- 16585349
TI  - Emergency contraception: to the editor.

PMID- 16585350
TI  - Emergency contraception.

PMID- 16585351
TI  - Perceived increase in mortality after process and policy changes implemented with
      computerized physician order entry.

PMID- 16585352
TI  - Perceived increase in mortality after process and policy changes implemented with
      computerized physician order entry.

PMID- 16585353
TI  - Perceived increase in mortality after process and policy changes implemented with
      computerized physician order entry.

PMID- 16585355
TI  - The folic acid debate continues.

PMID- 16585354
TI  - Failure to thrive as distinct from child neglect.

PMID- 16585356
TI  - Is appendicitis the only cause of an acute abdominal pain in childhood?

PMID- 16585357
TI  - Primary operative versus nonoperative therapy for pediatric empyema.

PMID- 16585358
TI  - Tobacco industry profits from smoking images in the movies.

PMID- 16585359
TI  - Are the costs attributable?

PMID- 16585360
TI  - Poor circulation, early brain injury, and the potential role of red cell
      transfusion in premature newborns.

PMID- 16585361
TI  - Extracorporeal shock wave therapy in the treatment of chronic tendinopathies.
AB  - Many clinical trials have evaluated the use of extracorporeal shock wave therapy
      for treating patients with chronic tendinosis of the supraspinatus, lateral
      epicondylitis, and plantar fasciitis. Although extracorporeal shock wave therapy
      has been reported to be effective in some trials, in others it was no more
      effective than placebo. The multiple variables associated with this therapy, such
      as the amount of energy delivered, the method of focusing the shock waves,
      frequency and timing of delivery, and whether or not anesthetics are used, makes
      comparing clinical trials difficult. Calcific tendinosis of the supraspinatus and
      plantar fasciitis have been successfully managed with extracorporeal shock wave
      therapy when nonsurgical management has failed. Results have been mixed in the
      management of lateral epicondylitis, however, and this therapy has not been
      effective in managing noncalcific tendinosis of the supraspinatus. Extracorporeal
      shock wave therapy has consistently been more effective with patient feedback,
      which enables directing the shock waves to the most painful area (clinical
      focusing), rather than with anatomic or image-guided focusing, which are used to
      direct the shock wave to an anatomic landmark or structure.

PMID- 16585362
TI  - Nontraumatic disorders of the clavicle.
AB  - Other than those resulting from trauma and arthritis, disorders of the clavicle
      are uncommon. Some nontraumatic disorders are found only in infancy and
      childhood, such as birth fracture, infantile cortical hyperostosis, congenital
      pseudarthrosis, cleidocranial dysplasia, and short clavicle syndrome. Other
      nontraumatic disorders occur in both children and adults; these include anterior
      subluxation of the sternoclavicular joint, Friedrich's disease, hypertrophic
      osteitis, chronic multifocal periosteitis and arthropathy, and osteomyelitis.
      Some nontraumatic clavicular disorders are found only in adults, such as distal
      osteolysis. Because the description and nomenclature of these disorders arise
      from several medical disciplines, they often are confusing. Until clear,
      distinguishing features are described, it is advisable to combine some of the
      entities. This is especially true of the nonsuppurative inflammatory disorders of
      the clavicle, which appear to fall under the heading of spondyloarthropathy.
      Treatment varies by disorder and may include symptomatic and expectant
      management, drug therapy, and nonsurgical or surgical treatment.

PMID- 16585363
TI  - Use of bisphosphonates to improve the durability of total joint replacements.
AB  - Total joint arthroplasty is very effective for improving the quality of life of
      patients with end-stage arthritis. Despite advances in materials, surgical
      technique, and rehabilitation regimens, joint replacements are still fraught with
      complications leading to their premature failure. Aseptic loosening and
      osteolysis are the primary causes of implant failure. Other reasons include early
      migration of components leading to instability, lack of ingrowth into implant
      porosities, and bone loss caused by stress shielding. Pharmaceutical agents used
      for preventing and managing postmenopausal osteoporosis (eg, bisphosphonates) may
      in the future play an important role in improving the long-term duration of joint
      arthroplasties. Early findings indicate that bisphosphonates upregulate bone
      morphogenetic protein-2 production and stimulate new bone formation. Because of
      their anabolic effect on osteoblasts, bisphosphonates have the potential to
      enhance bone ingrowth into implant porosities, prevent bone resorption under
      adverse conditions, and dramatically extend the long-term durability of joint
      arthroplasties. The long-term effects of bisphosphonate use on the mechanical
      properties of bone have not been adequately investigated. Along with improvements
      in implant design and material properties, bisphosphonates and other
      pharmaceutical agents may, in the near future, be part of the growing
      armamentarium that provides more durable joint arthroplasties.

PMID- 16585364
TI  - Spinal surgery and patient safety: a systems approach.
AB  - In every spinal procedure, identifying the specific patient, proper surgical
      site, and pathologic lesion for surgical intervention are crucial patient safety
      concerns. The 1999 Institute of Medicine report "To Err is Human" identified
      adverse events associated with surgery. Both the American Academy of Orthopaedic
      Surgeons and the North American Spine Society have had voluntary, systems-based
      programs in place for several years to address wrong patient, wrong procedure,
      and wrong site surgery. Beginning July 1, 2004, the Joint Commission on the
      Accreditation of Healthcare Organizations mandated that hospitals comply with the
      JCAHO Universal Protocol. In addition to surgical site marking, the protocol
      incorporates additional factors, such as calling a time out before skin incision
      to do a final systems check of patient identification, surgical site, records,
      imaging studies, equipment, and review of preoperative medication.

PMID- 16585365
TI  - Nontraumatic upper cervical spine instability in children.
AB  - The upper cervical spine begins at the base of the occiput, continues caudally to
      the C2-C3 disk space, and includes the occipitoatlantal and atlantoaxial joints.
      Nontraumatic upper cervical spine instability can result from abnormal
      development of osseous or ligamentous structures or from gradually increasing
      ligamentous laxity associated with connective tissue disorders. Such instability
      can lead to compression of the spinal cord during movement of the cervical spine.
      Establishing a correct diagnosis includes performing a thorough physical
      examination as well as evaluating radiographic relationships and measurements.
      Appropriate management of syndromes associated with instability of the upper
      cervical spine includes preventive care and recommendations for sports
      participation. Surgical treatment for the upper cervical spine includes a
      posterior surgical approach, used for instability, and the use of rigid plate
      implants, wiring, and bone graft materials to achieve a solid spinal fusion.

PMID- 16585366
TI  - The geographic incidence and treatment variation of common fractures of elderly
      patients.
AB  - Fractures of the hip, wrist, proximal humerus, and ankle frequently are observed
      among the elderly patient population in the United States. The Medicare patient
      population has shown dramatic geographic variation in the rates of these common
      fractures, with an increased incidence observed throughout the Southeast.
      Treatment (surgical versus nonsurgical) is also highly variable and dependent on
      the geographic location but not necessarily on the type of injury. Whereas
      regional variation in medical treatment may be attributed to variations in
      practice patterns, the etiology behind the dramatic variations in fractures is
      less well-defined and is likely multifactorial, related to environmental,
      occupational, genetic, or nutritional factors.

PMID- 16585367
TI  - On the horizon from the ORS.

PMID- 16585369
TI  - Postmastectomy lymphedema: a call for osteopathic medical research.

PMID- 16585368
TI  - Pectoralis major muscle injuries: evaluation and management.

PMID- 16585370
TI  - Avoiding antiretroviral-associated cytopenias.

PMID- 16585371
TI  - Recurring Limitations in OMT Research.

PMID- 16585372
TI  - Solving clinical problems osteopathically.

PMID- 16585374
TI  - Beyond OMT: time for a new chapter in osteopathic medicine?

PMID- 16585378
TI  - Center or periphery? The future of osteopathic principles and practices.

PMID- 16585379
TI  - Faith without works.

PMID- 16585380
TI  - Chronic kidney disease: the new silent killer.

PMID- 16585381
TI  - Gross range of motion in the cervical spine: the effects of osteopathic muscle
      energy technique in asymptomatic subjects.
AB  - Muscle energy technique is an established osteopathic manipulative intervention
      often used to treat somatic dysfunctions of the spine. There are little objective
      data to demonstrate its efficacy, however. To determine the efficacy of this
      osteopathic manipulative technique, the authors compared active cervical range of
      motion among asymptomatic young and middle-aged adults (n=18) before and after
      this treatment protocol, comparing those results against matched control subjects
      (n=14) who received sham manipulative treatment. Range of motion was measured in
      three planes (flexion/extension, lateral bending, rotation) on all subjects
      (N=32) using a motion-analysis system. Multiplanar gross cervical motion
      restrictions were diagnosed in this asymptomatic population. In the treatment
      group, cervical long restrictor muscles were treated with the muscle energy
      technique in the sagittal, frontal, and horizontal planes. The control group had
      relative restrictions addressed by means of a sham manipulative treatment
      protocol in which the barriers to motion were not challenged therapeutically. The
      muscle energy technique produced a significant increase in overall regional
      cervical range of motion in the treatment group (approximately 4 degrees) when
      compared with control subjects (P<.001). Significant differences were also
      observed in the magnitude of change in the three planes of movement (rotation,
      P<.002; lateral bending, P<.01), with flexion/extension being the least affected
      (P=.2). These data demonstrate that the application of the muscle energy
      technique can produce acute increases in the active cervical range of motion in
      asymptomatic subjects.

PMID- 16585382
TI  - New strategies for diagnosis and management of celiac disease.
AB  - Celiac disease is a gastrointestinal disorder characterized by inflammation,
      leading to injury to the mucosal lining of the small intestine. The inflammation
      occurs when gliadin, a protein found in such gluten-containing foods as wheat,
      rye, and barley, is ingested by genetically susceptible individuals. The mucosal
      damage and subsequent malabsorption of nutrients leads to various complications.
      Researchers estimate that more than 2 million people in the United States have
      celiac disease-a prevalence that is greater than was previously believed.
      Approximately 60,000 Americans are diagnosed annually with celiac disease. Until
      recently, diagnosis has been complicated by the fact that the indicators of
      celiac disease are nonspecific. However, because of the development of new, easy
      to-administer serology tests, diagnosis has become much less complicated. After
      conducting a review of the literature, the authors recommend a serologic testing
      sequence for diagnosis of celiac disease and urge that adults and children with
      an assortment of symptoms be tested for this disease. Common signs and symptoms
      of celiac disease include anemia, arthralgia, fatigue, infertility, neuropathy,
      and weight loss, in addition to such gastrointestinal symptomatology as abdominal
      pain, anorexia, bloating, constipation, and diarrhea. The only treatment for
      patients with celiac disease remains a gluten-free diet.

PMID- 16585383
TI  - Factors associated with high-severity disciplinary action by a state medical
      board: a Texas study of medical license revocation.
AB  - CONTEXT: There has been an increase in research evaluating factors associated
      with disciplinary action of physicians by state medical boards. However, factors
      related to the severity of disciplinary action are lacking. By investigating
      these factors while controlling for the type of violation, the authors sought to
      determine whether physician characteristics influenced the process of
      disciplinary action by state medical boards. METHODS: Physicians disciplined by
      the Texas Medical Board between January 1, 1989, and December 31, 1998, were
      included in this case-controlled study (N=1129). Multivariate logistic regression
      analysis was used to compute odds ratios (ORs) and 95% confidence intervals (CIs)
      for factors associated with license revocation, the most severe disciplinary
      action, compared with all other forms of disciplinary action combined. RESULTS:
      Anesthesiologists (OR, 2.45; 95% CI, 1.05-5.74), general practitioners (OR, 1.80;
      95% CI, 1.01-3.19), and psychiatrists (OR, 2.68; 95% CI, 1.41-5.13), as well as
      those with multiple disciplinary actions (OR, 1.91; 95% CI, 1.29-2.83) were most
      susceptible to license revocation. The more years a disciplined physician was in
      practice, the greater risk he or she had of license revocation (OR, 1.05; 95% CI,
      1.04-1.07). CONCLUSIONS: Factors associated with a greater likelihood of license
      revocation for physicians are: primary medical specialty, number of years in
      practice, and a history of multiple disciplinary actions.

PMID- 16585384
TI  - In vitro biophysical strain model for understanding mechanisms of osteopathic
      manipulative treatment.
AB  - CONTEXT: Normal physiologic movement, pathologic conditions, and osteopathic
      manipulative treatment (OMT) are believed to produce effects on the shape and
      proliferation of human fibroblasts. Studies of biophysically strained fibroblasts
      would be useful in producing a model of the cellular mechanisms underlying OMT.
      OBJECTIVE: To investigate the effects of acyclic in vitro biophysical strain on
      normal human dermal fibroblasts and observe potential changes in cellular shape
      and proliferation, as well as potential changes in cellular production of nitric
      oxide, interleukin (IL) 1beta, and IL-6. DESIGN AND METHODS: Randomized
      controlled trial. Human fibroblasts were subjected in vitro to control conditions
      (no strain) or biophysical strain of various magnitudes (10%-30% beyond resting
      length) and durations (12-72 hours). After control or strain stimuli, fibroblasts
      were analyzed for potential changes in cell shape, proliferative capacity, nitric
      oxide secretion, and cytokine (IL-1beta, IL-6) secretion. RESULTS: Low strain
      magnitudes (<20%) induced mild cellular rounding and pseudopodia truncation. High
      strain magnitudes (>20%) decreased overall cell viability and the mitogenic
      response, and induced cell membrane decomposition and pseudopodia loss. No basal
      or strain-induced secretion of IL-1beta was observed. Interleukin 6
      concentrations increased two-fold, while nitric oxide levels increased three
      fold, in cells strained at 10% magnitude for 72 hours (P<.05). CONCLUSION: Human
      fibroblasts respond to in vitro strain by secreting inflammatory cytokines,
      undergoing hyperplasia, and altering cell shape and alignment. The in vitro
      biophysical strain model developed by the authors is useful for simulating a
      variety of injuries, determining in vivo mediators of somatic dysfunction, and
      investigating the underlying mechanisms of OMT.

PMID- 16585385
TI  - Altered expression of ezrin in esophageal squamous cell carcinoma.
AB  - Ezrin is a membrane-cytoskeletal linker belonging to the ezrin-radixin-moesin
      (ERM) family and has been suggested to be involved in tumorigenesis. In this
      study we investigated ezrin expression pattern in normal esophageal mucosa and
      esophageal squamous cell carcinoma (ESCC) and the correlation with clinical
      characteristics. Immunohistochemical staining showed a tendency for ezrin to
      translocate from membrane to cytoplasm in the progression from normal epithelium
      to invasive carcinoma of the esophagus. By Western blot, we found that ezrin
      expression was downregulated in 13 ESCC specimens and upregulated in 36 others.
      Moreover, quantitative real-time RT-PCR demonstrated that ezrin mRNA level in
      normal esophageal mucosa was 3.60 +/- 3.60 times that in ESCC (p<0.001).
      Proliferating cell nuclear antigen (PCNA) expression level was higher in ezrin
      downregulated group compared with that in ezrin upregulated group (p<0.05).
      However, there was no significant association between ezrin expression and
      clinical characteristics. The results suggested that the localization of ezrin by
      immunohistochemistry may be useful in the diagnosis of ESCC, and ezrin may play a
      suppressive role in the tumorgenesis of ESCC.

PMID- 16585386
TI  - Caveolin-1 expression is associated with plaque formation in hypercholesterolemic
      rabbits.
AB  - Caveolin-1, the major structural protein of caveolae, is present in several cell
      types known to play a role in the development of atherosclerosis. In this study,
      the distribution and expression of caveolin-1 in the arterial walls were studied
      in hypercholesterolemic rabbits. Immunohistochemical results indicated that the
      staining intensity of caveolin-1 reached a high level in the arterial intima at 5
      weeks after high-cholesterol-diet treatment and decreased to a very low level at
      8 weeks when atheromatous plaques appeared. Western blot analysis showed that in
      rabbits fed a high-cholesterol diet for 5 weeks, the expression of caveolin-1
      reached its highest level and then decreased from 8 to 12 weeks. The
      proliferative activity of smooth muscle cells (SMCs) decreased to the lowest
      level at 5 weeks and then increased at 8 and 12 weeks. Nitric oxide synthase
      activity gradually decreased in animals fed a high-cholesterol diet throughout
      the experiment. These studies demonstrate that the change in abundance of
      caveolin-1 is associated with SMC proliferation in the formation of atheromatous
      plaque after hypercholesterolemia insult.

PMID- 16585387
TI  - Immunohistochemical study of cell proliferation, Bcl-2, p53, and caspase-3
      expression on preneoplastic changes induced by cadmium and zinc chloride in the
      ventral rat prostate.
AB  - This work was directed to evaluate immunoexpression of markers for apoptosis,
      resistance to apoptosis, and cell proliferation, as well as estimates of nuclear
      size in ventral prostate of rats treated with cadmium chloride and cadmium+zinc
      chloride because a possible protective effect of zinc has been postulated. The
      following variables were studied: volume fraction (VF) of Bcl-2 immunostaining,
      percentage of cells immunoreactive to proliferating cell nuclear antigen (LIPCNA)
      and p53 (LIp53), numerical density of caspase-3 immunoreactive cells (NV caspase
      3), and estimates of volume-weighted mean nuclear volume (upsilonV). The LIPCNA
      and VF of Bcl-2 were significantly increased in the treated animals. The
      dysplasias (independent of their origin) showed a significant increase of the
      LIp53, NV caspase-3, and upsilonV in comparison with normal acini from treated
      and control animals. It can be concluded that cell proliferation is enhanced in
      long-term cadmium-exposed rats, and exposure to zinc combined with cadmium had no
      effect on any of the variables studied when comparing with normal acini. The
      increase of nuclear upsilonV could indicate a more aggressive behavior for
      pretumoral lesions.

PMID- 16585388
TI  - Progression of plasminogen activator inhibitor-1 and fibrinogen levels in
      relation to incident type 2 diabetes.
AB  - BACKGROUND: Several studies have shown that fibrinolytic and coagulation
      abnormalities as well as low-grade inflammation predict cardiovascular disease
      and type 2 diabetes. We studied in the Insulin Resistance Atherosclerosis Study
      the relation of incident diabetes to dynamic changes of plasminogen activator
      inhibitor-1 (PAI-1) and fibrinogen. METHODS AND RESULTS: After a follow-up of 5.2
      years, diabetes developed in 140 (16.6%) of 843 individuals (57% women; mean age
      [range], 54.7 [40, 69] years) (converters versus nonconverters). Baseline and
      follow-up levels of PAI-1 and fibrinogen (demographically and smoking adjusted)
      were higher in converters versus nonconverters (mean [SE]): at baseline, 23.7
      ng/mL (1.5) versus 14.5 (0.4) and 286.2 mg/dL (4.8) versus 273.6 (2.1); at follow
      up, 45.3 ng/mL (3.2) versus 25.9 (0.8) and 292.0 mg/dL (5.6) versus 275.2 (2.5);
      all P<0.05. In a demographically and smoking-adjusted logistic regression model,
      the change in PAI-1 was related to incident diabetes (OR for a 1-SD change [CI],
      1.75 [1.37, 2.22]; P<0.001) after adjusting for baseline PAI-1 levels. After
      further adjusting for insulin sensitivity (SI) or waist, change in PAI-1 remained
      significantly related to incident diabetes (OR, 1.66 [1.28, 2.15], and 1.64
      [1.28, 2.10]; P<0.001). In contrast, change in fibrinogen was not significantly
      related to incident diabetes. CONCLUSIONS: Progression of PAI-1 levels over time,
      in addition to high baseline PAI-1 levels, is associated with incident diabetes.
      PAI-1 levels (but not fibrinogen) further increase with the rising glucose levels
      and the development of diabetes. These findings extend the current knowledge on
      the relation of fibrinolysis and coagulation abnormalities to the development of
      type 2 diabetes.

PMID- 16585389
TI  - Evidence of a dominant backward-propagating "suction" wave responsible for
      diastolic coronary filling in humans, attenuated in left ventricular hypertrophy.
AB  - BACKGROUND: Coronary blood flow peaks in diastole when aortic blood pressure has
      fallen. Current models fail to completely explain this phenomenon. We present a
      new approach-using wave intensity analysis-to explain this phenomenon in normal
      subjects and to evaluate the effects of left ventricular hypertrophy (LVH).
      METHOD AND RESULTS: We measured simultaneous pressure and Doppler velocity with
      intracoronary wires in the left main stem, left anterior descending, and
      circumflex arteries of 20 subjects after a normal coronary arteriogram. Wave
      intensity analysis was used to identify and quantify individual pressure and
      velocity waves within the coronary artery circulation. A consistent pattern of 6
      predominating waves was identified. Ninety-four percent of wave energy,
      accelerating blood forward along the coronary artery, came from 2 waves: first a
      pushing wave caused by left ventricular ejection-the dominant forward-traveling
      pushing wave; and later a suction wave caused by relief of myocardial
      microcirculatory compression-the dominant backward-traveling suction wave. The
      dominant backward-traveling suction wave (18.2+/-13.7 x 10(3) W m(-2)s(-1), 30%)
      was larger than the dominant forward-traveling pushing wave (14.3+/-17.6 x 10(3)
      W m(-2) s(-1), 22.3%, P =0.001) and was associated with a substantially larger
      increment in coronary blood flow velocity (0.51 versus 0.14 m/s, P <0.001). In
      LVH, the dominant backward-traveling suction wave percentage was significantly
      decreased (33.1% versus 26.9%, P =0.01) and inversely correlated with left
      ventricular septal wall thickness (r =-0.52, P <0.02). CONCLUSIONS: Six waves
      predominantly drive human coronary blood flow. Coronary flow peaks in diastole
      because of the dominance of a "suction" wave generated by myocardial
      microcirculatory decompression. This is significantly reduced in LVH.

PMID- 16585390
TI  - Effects of gap geometry on conduction through discontinuous radiofrequency
      lesions.
AB  - BACKGROUND: Gaps of sufficient cross-sectional dimensions within linear
      radiofrequency (RF) lesions may allow conduction through the lesion. The purpose
      of this study was to examine the effects of different gap geometries on
      conduction through discontinuous RF lesions. METHODS AND RESULTS: Radiofrequency
      lesions were created in isolated, perfused rabbit right ventricular (RV) free
      wall preparations to produce gaps with 3 different lesion geometries: straight,
      bifurcated, and angled (n=10 each group). Angled preparations contained 2 right
      angles within the conduction path. Optical mapping was used to assess
      bidirectional conduction through the myocardium before and after gap formation
      during pacing at 1000-, 400-, and 200-ms cycle lengths. Histological analysis was
      performed on each preparation after optical mapping. After lesion formation, 9 of
      10 straight gap preparations and 1 of 10 angled gap preparations demonstrated
      bidirectional conduction (P<0.001) at all cycle lengths. Nine of 10 bifurcated
      gap preparations demonstrated bidirectional conduction and 1 demonstrated
      unidirectional conduction at all cycle lengths. Two bifurcated gap preparations
      showed rate-dependent unidirectional 2:1 conduction. All unidirectional and rate
      dependent block occurred during impulse propagation in the direction of diverging
      arms of the bifurcation. The occurrence of bidirectional conduction in the gaps
      was associated with the gap geometry (P<0.0001). Histological analysis confirmed
      the continuity of viable myocardium transmurally throughout the length of the gap
      in each preparation. The sites of conduction block were demonstrated to be just
      after the first angle in the conduction path for angled gaps and at the branch
      point of a bifurcated gap. The predominant myofiber orientation was changed
      relative to the conduction path at angulations of the gaps. Flecainide (0.1
      micromol/L) produced bidirectional conduction block in straight and bifurcated
      gap preparations with bidirectional conduction at baseline. CONCLUSIONS:
      Conduction through discontinuities in RF lesions is associated with gap geometry.
      Complex gap geometry may allow for unidirectional and/or rate-dependent block.
      Gaps within RF lesions are susceptible to pharmacological blockade.

PMID- 16585391
TI  - Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular
      remodeling and failure after myocardial infarction in mice.
AB  - BACKGROUND: Mitochondrial oxidative stress and damage play major roles in the
      development and progression of left ventricular (LV) remodeling and failure after
      myocardial infarction (MI). We hypothesized that overexpression of the
      mitochondrial antioxidant, peroxiredoxin-3 (Prx-3), could attenuate this
      deleterious process. METHODS AND RESULTS: We created MI in 12- to 16-week-old,
      male Prx-3-transgenic mice (TG+MI, n=37) and nontransgenic wild-type mice (WT+MI,
      n=39) by ligating the left coronary artery. Prx-3 protein levels were 1.8 times
      higher in the hearts from TG than WT mice, with no significant changes in other
      antioxidant enzymes. At 4 weeks after MI, LV thiobarbituric acid-reactive
      substances in the mitochondria were significantly lower in TG+MI than in WT+MI
      mice (mean+/-SEM, 1.5+/-0.2 vs 2.2+/-0.2 nmol/mg protein; n=8 each, P<0.05). LV
      cavity dilatation and dysfunction were attenuated in TG+MI compared with WT+MI
      mice, with no significant differences in infarct size (56+/-1% vs 55+/-1%; n=6
      each, P=NS) and aortic pressure between groups. Mean LV end-diastolic pressures
      and lung weights in TG+MI mice were also larger than those in WT+sham-operated
      mice but smaller than those in WT+MI mice. Improvement in LV function in TG+MI
      mice was accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis,
      and apoptosis in the noninfarcted LV. Mitochondrial DNA copy number and complex
      enzyme activities were significantly decreased in WT+MI mice, and this decrease
      was also ameliorated in TG+MI mice. CONCLUSIONS: Overexpression of Prx-3
      inhibited LV remodeling and failure after MI. Therapies designed to interfere
      with mitochondrial oxidative stress including the antioxidant Prx-3 might be
      beneficial in preventing cardiac failure.

PMID- 16585392
TI  - Role of p90 ribosomal S6 kinase-mediated prorenin-converting enzyme in ischemic
      and diabetic myocardium.
AB  - BACKGROUND: Epidemiological data strongly indicate that diabetes increases the
      incidence of heart failure. Although the benefit of angiotensin-converting enzyme
      inhibitor (ACE-I) treatment during and after myocardial infarction has been found
      to be greater in diabetics than nondiabetics and activation of the renin
      angiotensin system (RAS) has been implicated, the molecular basis of these
      actions remains unclear. METHODS AND RESULTS: We generated transgenic mice with
      cardiac-specific overexpression of wild-type p90 ribosomal S6 kinase (WT-p90RSK
      Tg) and a dominant-negative form of p90RSK (DN-p90RSK-Tg). Recovery of cardiac
      function after ischemia/reperfusion in WT-p90RSK-Tg isolated mouse hearts was
      significantly impaired. Matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry revealed specific induction of prorenin-converting
      enzyme (PRECE) in WT-p90RSK-Tg mice. mRNA induction of PRECE was confirmed with
      serial angiotensinogen protein reduction after perfusion in WT-p90RSK-Tg mice,
      suggesting an increase of angiotensinogen cleavage and subsequent RAS activation
      in WT-p90RSK-Tg mice. We investigated the role of the RAS in WT-p90RSK-Tg animals
      after ischemia/reperfusion with the use of an ACE-I (captopril) and an
      angiotensin II type 1 receptor blocker (olmesartan). We did not observe any
      effect of these inhibitors in non-Tg littermate controls, thus corroborating
      other reports in rodents. In contrast, both captopril and olmesartan
      significantly improved cardiac function and reduced infarct size in WT-p90RSK-Tg
      mice. At 8 months of age, WT-p90RSK-Tg mice developed cardiac dysfunction. p90RSK
      activity and PRECE mRNA were both increased by streptozotocin-induced
      hyperglycemia in non-Tg littermate controls, whereas DN-p90RSK-Tg animals exposed
      to streptozotocin did not have PRECE induction. CONCLUSIONS: This study
      demonstrates the critical role of p90RSK in hyperglycemia-mediated myocardial
      PRECE induction, which may explain the augmentation of the RAS in diabetic hearts
      and provide an alternative therapeutic approach to treat diabetic cardiomyopathy.

PMID- 16585394
TI  - Kir3-based inward rectifier potassium current: potential role in atrial
      tachycardia remodeling effects on atrial repolarization and arrhythmias.
AB  - BACKGROUND: We previously characterized a novel K+ current (IKH) with properties
      of constitutively active acetylcholine-related current in dog atrium. I(KH) is
      sensitive to tertiapin-Q (IC50 approximately 10 nmol/L), a highly selective Kir3
      current blocker. This study assessed the role of IKH in atrial tachycardia (AT)
      remodeled canine left atrium (LA) with the use of tertiapin-Q as a probe. METHODS
      AND RESULTS: Dogs were subjected to 7 to 13 days of AT (400 bpm). Coronary
      perfused LA preparations were studied intact or subjected to cardiomyocyte
      isolation. IKH was recorded with patch-clamp methods. AT pacing increased time
      dependent hyperpolarization-activated current (IKH) at -110 mV from -1.8+/-0.3
      (control) to -3.4+/-0.5 pA/pF (AT) and the 100-nmol/L tertiapin-sensitive
      component from -1.5+/-0.4 (control) to -3.3+/-0.6 pA/pF (AT). Prolonged atrial
      tachyarrhythmias could be induced with single extrastimuli in AT-remodeled, but
      not control, preparations, reflecting the atrial fibrillation-promoting effects
      of AT remodeling. In AT-remodeled preparations, tachyarrhythmia duration averaged
      11.0+/-5.2 seconds, with a cycle length of 108+/-6 ms. Tertiapin-Q decreased
      tachyarrhythmia duration (to 0.6+/-0.1 second; P<0.001) and increased
      tachyarrhythmia cycle length (to 175+/-10 ms; P<0.001). Atrial action potential
      duration (APD) was increased 65+/-6% by tertiapin in AT-remodeled hearts versus
      19+/-2% (P<0.001) in control. In 2 AT-remodeled preparations, tachyarrhythmia
      lasted uninterrupted for >20 minutes; tertiapin-Q slowed and then terminated
      arrhythmia in both. Tertiapin had no effect on left ventricular cardiomyocyte
      currents or APD. CONCLUSIONS: AT remodeling increases IKH, and a highly selective
      Kir3 current antagonist, tertiapin-Q, increases APD and suppresses atrial
      tachyarrhythmias in AT-remodeled preparations without affecting ventricular
      electrophysiology. Constitutive acetylcholine-related K+ current contributes to
      AT-remodeling effects in dogs and is a potentially interesting antiarrhythmic
      target.

PMID- 16585393
TI  - Influence of preoperative left ventricular contractile reserve on postoperative
      ejection fraction in low-gradient aortic stenosis.
AB  - BACKGROUND: Dobutamine stress hemodynamics (DSH) has the potential to stratify
      operative risk in low-gradient aortic stenosis (AS), but little is known about
      the relation between left ventricle contractile reserve and postoperative left
      ventricular ejection fraction (LVEF). We sought to assess the value of DSH to
      predict postoperative improvement in LVEF. METHODS AND RESULTS: Sixty-six
      consecutive patients with symptomatic severe AS (aortic valve area < or =1 cm2),
      LVEF < or =40%, and mean pressure gradient < or =40 mm Hg prospectively enrolled
      in the French multicenter study on low-gradient AS and who survived to aortic
      valvular replacement (AVR) were included. Preoperative contractile reserve was
      present in 46 patients (group I; 70%) and absent in 20 patients (group II; 30%).
      In the overall sample, 58% of patients improved by 2 New York Heart Association
      (NYHA) classes after AVR. Mean LVEF improved from 29+/-6% to 47+/-11% (P<0.0001).
      LVEF improved by > or =10 EF units in 38 patients (83%) in group I and in 13
      patients (65%) in group II. Mean LVEF improvement was similar in the 2 groups
      (19+/-10% versus 17+/-11%; P=0.54). On multivariable analysis, multivessel
      coronary artery disease (P=0.05) and baseline mean transaortic pressure gradient
      (P=0.01) were related to LVEF improvement, whereas contractile reserve was not.
      CONCLUSIONS: LVEF increases in the majority of patients with low-gradient AS who
      survive after AVR. Although the absence of contractile reserve on DSH is related
      to high operative mortality, it does not predict the absence of LVEF recovery in
      patients surviving to AVR. These data further support the concept that surgery
      should not be contraindicated on the basis of absence of contractile reserve
      alone.

PMID- 16585395
TI  - Cardiology patient page. Catheter ablation of atrial fibrillation.

PMID- 16585396
TI  - Images in cardiovascular medicine. Acute myocardial infarction caused by
      extension of a proximal aortic dissection flap into the right coronary artery: an
      intracoronary ultrasound image.

PMID- 16585397
TI  - Images in cardiovascular medicine. "Shock advised": inappropriate public access
      defibrillation.

PMID- 16585398
TI  - Images in cardiovascular medicine. Magnetic resonance imaging and computed
      tomography findings in arrhythmogenic right ventricular cardiomyopathy.

PMID- 16585399
TI  - Letter regarding article by Katzen et al, "endovascular repair of abdominal and
      thoracic aortic aneurysms".

PMID- 16585400
TI  - A view from Ukraine.

PMID- 16585401
TI  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia: clinical impact of
      molecular genetic studies.

PMID- 16585402
TI  - Is clopidogrel cardiovascular medicine's double-edged sword?

PMID- 16585403
TI  - Endothelial nitric oxide synthase in vascular disease: from marvel to menace.
AB  - Nitric oxide (NO*) is an important protective molecule in the vasculature, and
      endothelial NO* synthase (eNOS) is responsible for most of the vascular NO*
      produced. A functional eNOS oxidizes its substrate L-arginine to L-citrulline and
      NO*. This normal function of eNOS requires dimerization of the enzyme, the
      presence of the substrate L-arginine, and the essential cofactor (6R)-5,6,7,8
      tetrahydro-L-biopterin (BH4), one of the most potent naturally occurring reducing
      agents. Cardiovascular risk factors such as hypertension, hypercholesterolemia,
      diabetes mellitus, or chronic smoking stimulate the production of reactive oxygen
      species in the vascular wall. Nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidases represent major sources of this reactive oxygen species and have been
      found upregulated and activated in animal models of hypertension, diabetes, and
      sedentary lifestyle and in patients with cardiovascular risk factors. Superoxide
      (O2*-) reacts avidly with vascular NO* to form peroxynitrite (ONOO-). The
      cofactor BH4 is highly sensitive to oxidation by ONOO-. Diminished levels of BH4
      promote O2*- production by eNOS (referred to as eNOS uncoupling). This
      transformation of eNOS from a protective enzyme to a contributor to oxidative
      stress has been observed in several in vitro models, in animal models of
      cardiovascular diseases, and in patients with cardiovascular risk factors. In
      many cases, supplementation with BH4 has been shown to correct eNOS dysfunction
      in animal models and patients. In addition, folic acid and infusions of vitamin C
      are able to restore eNOS functionality, most probably by enhancing BH4 levels as
      well.

PMID- 16585404
TI  - Sleep apnea in hypertension: when, how, and why should we treat?

PMID- 16585405
TI  - Alcohol and hypertension: an update.

PMID- 16585407
TI  - Retinal vessel narrowing: a prehypertensive or masked hypertensive state?

PMID- 16585408
TI  - Rho kinase polymorphism influences blood pressure and systemic vascular
      resistance in human twins: role of heredity.
AB  - The Rho/Rho kinase (ROCK) pathway is implicated in experimental hypertension. We,
      therefore, explored the role of ROCK2 genetic variation in human blood pressure
      (BP) regulation, exploiting the advantages of a human twin sample to probe
      heritability. The focus of this work is the common nonsynonymous variant at
      ROCK2: Thr431Asn. Cardiovascular and autonomic traits displayed substantial
      heritability (from approximately 33% to 71%; P<0.05). The Asn/Asn genotype
      (compared with Asn/Thr or Thr/Thr) was associated with greater resting systolic
      (P<0.001), diastolic (P<0.0001), and mean BP (P<0.0001); allelic variation at
      ROCK2 accounted for up to approximately 5% of BP variation (P<0.0001). Systemic
      vascular resistance was higher in Asn/Asn individuals (P=0.049), whereas cardiac
      output, large artery compliance, and vasoactive hormone secretion were not
      different. Coupling of the renin-angiotensin system to systemic resistance and BP
      was diminished in Asn/Asn homozygotes, suggesting genetic pleiotropy of
      Thr431Asn, confirmed by bivariate genetic analyses. The Asn/Asn genotype also
      predicted higher BP after environmental (cold) stress. The rise in heart rate
      after cold was less pronounced in Asn/Asn individuals, consistent with intact
      baroreceptor function, and baroreceptor slope was not influenced by genotype.
      Common genetic variation (Thr431Asn) at ROCK2 predicts increased BP, systemic
      vascular resistance (although not large artery compliance), and resistance in
      response to the endogenous renin-angiotensin system, indicating a resistance
      vessel-based effect on elevated BP. The results suggest that common variation in
      ROCK2 exerts systemic resistance-mediated changes in BP, documenting a novel
      mechanism for human circulatory control, and suggesting new possibilities for
      diagnostic profiling and treatment of subjects at risk of developing
      hypertension.

PMID- 16585409
TI  - Sleep and hypertension: burning the candle at both ends really is hazardous to
      your health.

PMID- 16585410
TI  - Short sleep duration as a risk factor for hypertension: analyses of the first
      National Health and Nutrition Examination Survey.
AB  - Depriving healthy subjects of sleep has been shown to acutely increase blood
      pressure and sympathetic nervous system activity. Prolonged short sleep durations
      could lead to hypertension through extended exposure to raised 24-hour blood
      pressure and heart rate, elevated sympathetic nervous system activity, and
      increased salt retention. Such forces could lead to structural adaptations and
      the entrainment of the cardiovascular system to operate at an elevated pressure
      equilibrium. Sleep disorders are associated with cardiovascular disease, but we
      are not aware of any published prospective population studies that have shown a
      link between short sleep duration and the incidence of hypertension in subjects
      without apparent sleep disorders. We assessed whether short sleep duration would
      increase the risk for hypertension incidence by conducting longitudinal analyses
      of the first National Health and Nutrition Examination Survey (n=4810) using Cox
      proportional hazards models and controlling for covariates. Hypertension
      incidence (n=647) was determined by physician diagnosis, hospital record, or
      cause of death over the 8- to 10-year follow-up period between 1982 and 1992.
      Sleep durations of < or =5 hours per night were associated with a significantly
      increased risk of hypertension (hazard ratio, 2.10; 95% CI, 1.58 to 2.79) in
      subjects between the ages of 32 and 59 years, and controlling for the potential
      confounding variables only partially attenuated this relationship. The increased
      risk continued to be significant after controlling for obesity and diabetes,
      which was consistent with the hypothesis that these variables would act as
      partial mediators. Short sleep duration could, therefore, be a significant risk
      factor for hypertension.

PMID- 16585411
TI  - Electrocardiographic QRS duration and the risk of congestive heart failure: the
      Framingham Heart Study.
AB  - Prolonged electrocardiographic QRS duration is frequently observed in congestive
      heart failure (CHF) patients. We hypothesized that CHF risk increases with longer
      QRS interval in individuals free of CHF. We evaluated 1759 Framingham Study
      participants (mean age, 69 years; 63% women) without prior myocardial infarction
      or CHF who attended a routine examination. QRS duration was analyzed as a
      continuous (log-transformed) and a categorical variable [referent, <100 ms;
      incomplete bundle branch block (BBB), 100 to 119 ms; complete BBB, > or =120 ms].
      During follow-up (mean, 12.7 years), 324 participants (205 women) developed CHF.
      CHF incidence increased across the 3 baseline QRS duration categories in both
      sexes. Each SD increment in log-QRS duration was associated with a multivariable
      adjusted 23% increase in CHF risk [95% confidence interval [CI] 8% to 38%;
      P<0.001]. In time- dependent models with QRS category and risk factors updated
      every 2 years, incomplete BBB was associated with a 1.4-fold (95% CI, 1.05 to
      1.96; P=0.03) and complete BBB with a 1.7-fold (95% CI, 1.28 to 2.35; P<0.001)
      risk of CHF. These associations were maintained on adjustment for baseline left
      ventricular mass. In our community-based sample, longer electrocardiographic QRS
      was associated with increased CHF risk, consistent with the hypothesis that
      depolarization delay may increase CHF risk.

PMID- 16585412
TI  - Effects of continuous positive airway pressure versus supplemental oxygen on 24
      hour ambulatory blood pressure.
AB  - Obstructive sleep apnea (OSA) is associated with recurrent episodes of nocturnal
      hypoxia and increased risk for development of systemic hypertension. Prior
      studies have been limited, however, in their ability to show reduction in blood
      pressure after continuous positive airway pressure (CPAP) therapy, and the effect
      of supplemental oxygen alone on blood pressure in OSA has not been evaluated. We
      performed a randomized, double-blind, placebo-controlled study comparing the
      effects of 2 weeks of CPAP versus sham-CPAP versus supplemental nocturnal oxygen
      on 24-hour ambulatory blood pressure in 46 patients with moderate-severe OSA. We
      found that 2 weeks of CPAP therapy resulted in a significant reduction in daytime
      mean arterial and diastolic blood pressure and nighttime systolic, mean, and
      diastolic blood pressure (all Ps <0.05). Although nocturnal supplemental oxygen
      therapy improved oxyhemoglobin saturation, it did not affect blood pressure. We
      conclude that CPAP therapy reduces both daytime and nighttime blood pressure in
      patients with OSA, perhaps through mechanisms other than improvement of nocturnal
      oxyhemoglobin saturation.

PMID- 16585413
TI  - Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide:
      biomarkers for mortality in a large community-based cohort free of heart failure.
AB  - Recent studies report that, in the absence of heart failure and renal failure,
      plasma B-type natriuretic peptide (BNP) has prognostic value for mortality. We
      sought to confirm and extend these previous studies to assess BNP, measured by 3
      distinct assays, as a biomarker for mortality in a strategy to enhance efforts at
      primary prevention and to better understand the clinical phenotype of such
      subjects at risk. We used a community-based cohort of 2042 subjects from Olmsted
      County, Minn, and individuals with heart or renal failure were excluded. BNP was
      assessed using 3 assays including Biosite and Shionogi for mature, biologically
      active BNP and the Roche assay for apparently nonbiologically active amino
      terminal pro-BNP (NT-proBNP). Thorough echocardiographic and clinical data were
      recorded for all of the participants. Median follow-up for mortality was 5.6
      years. BNP by all 3 of the assays was predictive of mortality. NT-proBNP and
      Biosite assays remained significant even after adjustment for traditional
      clinical risk factors and echocardiographic abnormalities including left
      ventricular hypertrophy and diastolic dysfunction. Echocardiography documented
      widespread structural changes in those with increasing BNP levels yet below
      levels observed in heart failure. We report in a large, well-characterized
      community-based cohort, free of heart failure, the first study to compare 3
      distinct BNP assays as biomarkers for mortality in the same cohort. Our findings
      confirm the potential use of NT-proBNP and BNP biomarkers for future events and
      underscore that these peptides may also serve as biomarkers for underlying
      cardiac remodeling secondary to diverse cardiovascular disease entities.

PMID- 16585414
TI  - Different impact of the metabolic syndrome on left ventricular structure and
      function in hypertensive men and women.
AB  - Metabolic syndrome (MS) is increasingly recognized as an important cardiovascular
      risk factor in hypertension, but its influence on left ventricular (LV) mass and
      function in the 2 genders has not been specifically addressed. Among 618
      nondiabetic, untreated hypertensive subjects, echocardiographically detected LV
      mass was significantly greater in subjects with MS. A significant interaction was
      observed between sex and the MS (P<0.003 for the multiplicative interaction
      term). Compared with women without the MS, those with the syndrome had a 24%
      greater LV mass (49.5+/-12 versus 40.0+/-10 g x m(-2.7); P<0.001), whereas the
      difference was only 9% in men (50.3+/-12 versus 46.1+/-10 g x m(-2.7); P=0.003).
      A greater prevalence of LV hypertrophy was found in women (37% versus 14%;
      P<0.001) but not in men (39% versus 29%; P=0.09) with the MS. After adjustment
      for the effect of age, body mass index, 24-hour systolic blood pressure, and
      several confounders, the MS was independently associated with a greater LV mass
      index in women (regression coefficient, 4.80; P<0.001) but not in men. Women with
      the MS also had a greater LV relative wall thickness (0.42+/-0.07 versus 0.39+/
      0.07; P=0.004) and a depressed afterload-corrected midwall fractional shortening
      (94.0+/-12% versus 101.0+/-13%; P<0.001) than women without the syndrome, whereas
      no differences emerged in men. We conclude that, in untreated hypertension, MS
      has a different impact on LV hypertrophy and function in men and women. The
      effect of MS is more pronounced in women and is partly independent from the
      effect of several hemodynamic and nonhemodynamic determinants of LV mass.

PMID- 16585415
TI  - Abnormalities of retinal microvascular structure and risk of mortality from
      ischemic heart disease and stroke.
AB  - Abnormalities of the retinal microcirculation are found in hypertension and
      diabetes and predict cardiovascular mortality. This study examined the
      relationship between abnormalities of the retinal microvasculature and death from
      ischemic heart disease (IHD) and stroke. A population-based, nested case-control
      study was undertaken within the Beaver Dam Eye Study. Subjects (43 to 74 years)
      who died of IHD (n=126) or stroke (n=28) over a 10-year period were age and
      gender matched with controls subjects (n=528; case:control matching,
      approximately 1:4). Retinal photographs of cases and controls were digitized and
      analyzed using a computer-based technique. Increased risk of IHD death was
      associated with a suboptimal relationship of arteriolar diameters at bifurcation
      (P=0.02 unadjusted) and decreased retinal arteriolar tortuosity (P=0.011
      unadjusted). These associations remained significant after adjustment for age,
      sex, past history of cardiovascular disease, and other known cardiovascular risk
      factors. Increased arteriolar length:diameter ratio, a measure of generalized
      arteriolar narrowing, was associated with increased stroke mortality (P=0.02
      unadjusted). This association was independent of age and gender but was
      attenuated by adjustment for systolic blood pressure (P=0.15). Other quantitative
      measures of the retinal microvascular network (eg, venular tortuosity and
      arteriolar and venular bifurcation angle) were not associated with death from IHD
      or stroke. Retinal microvascular abnormalities are predictive of death from IHD
      and stroke. A detailed assessment of the retinal microvascular network from
      digitized photographs may be useful in the noninvasive assessment of target organ
      damage and cardiovascular risk.

PMID- 16585416
TI  - Office and ambulatory blood pressure are independently associated with
      albuminuria in older subjects with type 2 diabetes.
AB  - Blood pressure strongly predicts microalbuminuria and later progression to renal
      failure in people with diabetes. Ambulatory blood pressure monitoring seems to be
      superior to office blood pressure in predicting progression to microalbuminuria
      in type 1 diabetes. The associations of ambulatory blood pressure with office
      blood pressure and microalbuminuria in type 2 diabetes remain unclear. We studied
      the association of office blood pressure taken with an automated device and
      ambulatory blood pressure with spot urine albumin:creatinine ratio in 1180 older
      people with type 2 diabetes participating in the Informatics for Diabetes
      Education and Telemedicine Study. Office and awake systolic blood pressure were
      independently associated with albuminuria (P<0.001 for both) in a multivariate
      linear regression analysis that adjusted for age, gender, duration of diabetes,
      hemoglobin A1c, number of antihypertensive medications, and use of an angiotensin
      converting enzyme inhibitor or angiotensin receptor blocker. Twelve percent of
      participants had well-controlled office blood pressure but not ambulatory blood
      pressure, whereas 14% had well-controlled ambulatory but not office blood
      pressure. The prevalence of microalbuminuria and macroalbuminuria in these
      subgroups was intermediate between those with well-controlled or uncontrolled
      blood pressure by both methods. We found, in a multiethnic group of older
      subjects with type 2 diabetes, that office systolic blood pressure and awake
      systolic ambulatory blood pressure exhibited independent associations with degree
      of albuminuria.

PMID- 16585417
TI  - Longitudinal mitral annulus velocities are reduced in hypertensive subjects with
      or without left ventricle hypertrophy.
AB  - Normotensive and hypertensive subjects with and without left ventricular (LV)
      hypertrophy (LV mass index [LVMI] >51 g/m(2.7)) were examined by conventional
      echocardiography and tissue Doppler imaging of mitral annulus motion. The
      subgroups included nonobese normotensive subjects (n=16; age 51+/-9 years; 11
      female; systolic blood pressure [SBP] 109+/-11 mm Hg, body mass index [BMI] 24+/
      2.7 kg/m2; LVMI 32+/-5.5 g/m(2.7)), nonobese hypertensive subjects without LV
      hypertrophy (n=16; age 54+/-12 years; 12 female; SBP 166+/-15 mm Hg; BMI 25+/-2.7
      kg/m2; LVMI 42+/-5.5 g/m(2.7)), and hypertensive subjects with LV hypertrophy
      (n=22; age 56+/-10 years; 10 female; SBP 181+/-19 mm Hg; BMI 26+/-2.3 kg/m2; LVMI
      69+/-16 g/m(2.7)). Ejection fraction was comparable among the subgroups, but
      midwall fractional shortening was reduced in hypertensive subjects with LV
      hypertrophy (approximately 26%). Isovolumic relaxation time was increased in
      subjects with LV hypertrophy, whereas mitral wave A velocity was increased in
      hypertensive subjects with and without LV hypertrophy. Tissue Doppler imaging
      mitral annulus systolic (SM) and diastolic (EM) velocities were reduced in
      subjects with and without LV hypertrophy compared with normotensive subjects.
      There was a positive correlation between SM and EM (r=0.68; P<0.0001) and
      negative correlations between these 2 variables and LVMI (SM, r=-0.41; P=0.002;
      EM, r=-0.56; P<0.0001). Thus, reductions in mitral annulus systolic and diastolic
      velocities parallel increases in LV mass in hypertensive subjects, beginning at
      LV mass within the clinically defined normal values.

PMID- 16585418
TI  - Prorenin: back into the arena.

PMID- 16585420
TI  - Understanding diastolic heart failure with preserved ejection fraction: choosing
      the right model.

PMID- 16585419
TI  - Nonproteolytic activation of prorenin contributes to development of cardiac
      fibrosis in genetic hypertension.
AB  - In contrast to proteolytic activation of inactive prorenin by cleavage of the N
      terminal 43 residue peptide, we found that prorenin is activated without
      proteolysis by binding of the prorenin receptor to the pentameric "handle region"
      I(11P)LLKK(15P). We hypothesized that such activation occurs in hypertensive rats
      and causes cardiac renin-angiotensin system (RAS) activation and end-organ
      damage. To test this hypothesis, we devised methods of specifically inhibiting
      nonproteolytic activation by decapeptide spanning the pentameric handle region
      peptide as a decoy. In stroke-prone spontaneously hypertensive rats (SHRsp) fed a
      high-salt diet, arterial pressure started to rise significantly with a marked
      increase in the cardiac prorenin receptor mRNA level at 8 weeks of age, and
      cardiac fibrosis had developed by 12 weeks of age. By immunohistochemistry using
      antibodies to the active site of the renin molecule, we demonstrated increased
      proteolytic or nonproteolytic activation of prorenin in the heart but not in
      plasma of SHRsp. Continuous subcutaneous administration of the handle region
      peptide completely inhibited the increased staining by antibodies to the active
      site of the renin molecule, indicating the increased nonproteolytic but not
      proteolytic activation of prorenin in the heart of SHRsp. Administration of the
      handle region peptide also inactivated tissue RAS without affecting circulating
      RAS or arterial pressure and significantly attenuated the development and
      progression of cardiac fibrosis. These results clearly demonstrate the
      significant role of nonproteolytically activated tissue prorenin in tissue RAS
      activation leading to cardiac fibrosis and significant inhibition of the cardiac
      damage produced by chronic infusion of the handle region peptide.

PMID- 16585421
TI  - New mass spectrometric assay for angiotensin-converting enzyme 2 activity.
AB  - A novel assay was developed for evaluation of mouse angiotensin-converting enzyme
      (ACE) 2 and recombinant human ACE2 (rACE2) activity. Using surface-enhanced laser
      desorption/ionization time of flight mass spectrometry (MS) with ProteinChip
      Array technology, ACE1 and ACE2 activity could be measured using natural peptide
      substrates. Plasma from C57BL/6 mice, kidney from wild-type and ACE2 knockout
      mice, and rACE2 were used for assay validation. Plasma or tissue extracts were
      incubated with angiotensin I (Ang I; 1296 m/z) or angiotensin II (Ang II; 1045
      m/z). Reaction mixtures were spotted onto the ProteinChips WCX2 and peptides
      detected using surface-enhanced laser desorption/ionization time of flight MS. MS
      peaks for the substrates, Ang I and Ang II, and the generated peptides, Ang (1-7)
      and Ang (1-9), were monitored. The ACE2 inhibitor MLN 4760 (0.01 to 100
      micromol/L) significantly inhibited rACE2 activity (IC50=3 nmol/L). Ang II was
      preferably cleaved by rACE2 (km=5 mumol/L), whereas Ang I was not a good
      substrate for rACE2. There was no detectable ACE2 activity in plasma. Assay
      specificity was validated in a model of ACE2 gene deletion. In kidney extract
      from ACE2-deficient mice, there was no generation of Ang (1-7) from Ang II.
      However, Ang (1-7) was produced when Ang I was used as a substrate. In
      conclusion, we developed a specific and sensitive assay for ACE2 activity, which
      used the natural endogenous peptide substrate Ang II. This approach allows for
      the rapid screening for ACE2, which has applications in drug testing, high
      throughput enzymatic assays, and identification of novel substrates/inhibitors of
      the renin-angiotensin system.

PMID- 16585422
TI  - Folate supplementation during pregnancy improves offspring cardiovascular
      dysfunction induced by protein restriction.
AB  - Dietary protein restriction in the rat compromises the maternal cardiovascular
      adaptations to pregnancy and leads to raised blood pressure and endothelial
      dysfunction in the offspring. In this study we have hypothesized that dietary
      folate supplementation of the low-protein diet will improve maternal vascular
      function and also restore offspring cardiovascular function. Pregnant Wistar rats
      were fed either a control (18% casein) or protein-restricted (9% casein) diet +/
      5 mg/kg folate supplement. Function of isolated maternal uterine artery and small
      mesenteric arteries from adult male offspring was assessed, systolic blood
      pressure recorded, and offspring thoracic aorta levels of endothelial nitric
      oxide (NO) synthase mRNA measured. In the uterine artery of late pregnancy dams,
      vasodilatation to vascular endothelial growth factor was attenuated in the
      protein-restricted group but restored with folate supplementation, as was
      isoprenaline-induced vasodilatation (P<0.05). In male offspring, protein
      restriction during pregnancy led to raised systolic blood pressure (P<0.01),
      impaired acetylcholine-induced vasodilatation (P<0.01), and reduced levels of
      endothelial NO synthase mRNA (P<0.05). Maternal folate supplementation during
      pregnancy prevented this elevated systolic blood pressure associated with a
      protein restriction diet. With folate supplementation, endothelium-dependent
      vasodilatation and endothelial NO synthase mRNA levels were not significantly
      different from either the control or protein-restricted groups. Maternal folate
      supplementation of the control diet had no effect on blood pressure or
      vasodilatation. This study supports the hypothesis that folate status in
      pregnancy can influence fetal development and, thus, the risks of cardiovascular
      disease in the next generation. The concept of developmental origins of adult
      disease focuses predominately on fetal life but must also include a role for
      maternal cardiovascular function.

PMID- 16585423
TI  - Development of heart failure in chronic hypertensive Dahl rats: focus on heart
      failure with preserved ejection fraction.
AB  - The impact of hypertension on left ventricular (LV) structure, pump function, and
      heart failure in Dahl salt-sensitive rats is poorly characterized but
      hypothesized to yield insights into the pathophysiology of heart failure with
      normal or preserved ejection fraction. Eighty Dahl salt-sensitive rats were fed
      either a high-salt (HS) or low-salt (LS, controls) diet starting at age 7 weeks.
      Ventricular properties were measured by echocardiography, hemodynamics and end
      systolic and end-diastolic pressure-volume relationships (ESPVR and EDPVR,
      respectively). Compared with LS controls, HS rats developed severe hypertension
      and LV hypertrophy. At week 12, HS rats developed passive diastolic dysfunction
      (leftward/upward shifted EDPVR, increased chamber stiffness) with reductions in
      end-diastolic volume. However, the ESPVR also shifted upward (enhanced end
      systolic function) so that overall pump function was enhanced compared with LS,
      and there was no change in end-diastolic pressure (EDP). At 16 and 20 weeks, HS
      hearts enlarged so that end-diastolic volumes and EDPVRs became similar to the
      respective age-matched LS controls. Concomitantly, the ESPVRs and overall pump
      function curves also moved toward controls, and ejection fraction declined.
      Despite normal or enhanced overall pump function at these times, EDP and wet lung
      weight increased, indicative of development of heart failure. In the Dahl salt
      sensitive rat, which pathophysiologically retains salt and water, the development
      of heart failure (increased EDP and wet lung weight) is dissociated from changes
      in passive diastolic and active systolic properties. These observations suggest
      that a volume overload sate plays an important pathophysiological role in
      development of heart failure despite preserved overall ventricular pump function
      in this model of chronic hypertension.

PMID- 16585424
TI  - Practical treatment information for schizophrenia.

PMID- 16585425
TI  - Recognizing traumatic dissociation.

PMID- 16585426
TI  - Free lunch?

PMID- 16585427
TI  - Conflict of interest.

PMID- 16585428
TI  - Stimulating: prescribing amidst controversy.

PMID- 16585429
TI  - Substance P: a neuropeptide.

PMID- 16585430
TI  - Recent trends in stimulant medication use among U.S. children.
AB  - OBJECTIVE: Stimulant medications, such as methylphenidate and amphetamines, are
      commonly prescribed to treat attention deficit hyperactivity disorder. Stimulant
      use increased fourfold from 1987 (0.6%) to 1996 (2.4%) among subjects 18-year-old
      and younger in the U.S. The aim of this study was to determine whether pediatric
      use of stimulants continued to rise during the period 1997-2002. METHOD: The
      Medical Expenditure Panel Survey (MEPS) database for the years 1997-2001 was
      analyzed. The MEPS is a yearly survey of a nationally representative sample of
      civilian, noninstitutionalized U.S. households, conducted by the U.S. Agency for
      Health Care Research and Quality. Previously reported estimates from the 1996
      MEPS and the 1987 National Medical Expenditure Survey, the predecessor to MEPS,
      were also replicated to compare recent trends to changes between 1987 and 1996.
      RESULTS: The prevalence use of stimulants among subjects under 19 years of age
      was 2.7% (95% C.I. 2.3-3.1) in 1997 and 2.9% (95% C.I. 2.5-3.3) in 2002, with no
      statistically significant change during these 6 years. Likewise, when pooling
      data across years and comparing the rate in 1997-1998 (2.8%) with the rate in
      2001-2002 (3.0%), no statistically significant changes emerged. Use was highest
      among 6-12 year olds (4.8% in 2002), as compared with 3.2% among 13-19 year olds
      and 0.3% among children under 6. An estimated 2.2 million (95% C.I. 1.9-2.6)
      children received stimulant medication in 2002 as compared to 2.0 million (95%
      C.I. 1.7-2.3) in 1997. CONCLUSIONS: The steep increase in the utilization of
      stimulants among children 18 years and younger that occurred over the 1987-1996
      period attenuated in the following years through 2002, and has remained stable
      among very young children.

PMID- 16585431
TI  - Posttraumatic stress disorder among military returnees from Afghanistan and Iraq.

PMID- 16585432
TI  - Prescription drug dependence and evolving beliefs about chronic pain management.

PMID- 16585433
TI  - Can psychiatrists recognize mental illness in paintings?

PMID- 16585434
TI  - Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in
      patients with chronic schizophrenia who did not respond to prior atypical
      antipsychotic treatment.
AB  - OBJECTIVE: When a schizophrenia patient has an inadequate response to treatment
      with an antipsychotic drug, it is unclear what other antipsychotic to switch to
      and when to use clozapine. In this study, the authors compared switching to
      clozapine with switching to another atypical antipsychotic in patients who had
      discontinued treatment with a newer atypical antipsychotic in the context of the
      Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE)
      investigation. METHOD: Ninety-nine patients who discontinued treatment with
      olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the
      trials, primarily because of inadequate efficacy, were randomly assigned to open
      label treatment with clozapine (N=49) or blinded treatment with another newer
      atypical antipsychotic not previously received in the trial (olanzapine [N=19],
      quetiapine [N=15], or risperidone [N=16]). RESULTS: Time until treatment
      discontinuation for any reason was significantly longer for clozapine
      (median=10.5 months) than for quetiapine (median=3.3), or risperidone
      (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation
      because of inadequate therapeutic effect was significantly longer for clozapine
      than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive
      and Negative Syndrome Scale total scores had decreased more in patients treated
      with clozapine than in patients treated with quetiapine or risperidone but not
      olanzapine. One patient treated with clozapine developed agranulocytosis, and
      another developed eosinophilia; both required treatment discontinuation.
      CONCLUSIONS: For these patients with schizophrenia who prospectively failed to
      improve with an atypical antipsychotic, clozapine was more effective than
      switching to another newer atypical antipsychotic. Safety monitoring is necessary
      to detect and manage clozapine's serious side effects.

PMID- 16585435
TI  - Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients
      with chronic schizophrenia following discontinuation of a previous atypical
      antipsychotic.
AB  - BACKGROUND: In the treatment of schizophrenia, changing antipsychotics is common
      when one treatment is suboptimally effective, but the relative effectiveness of
      drugs used in this strategy is unknown. This randomized, double-blind study
      compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had
      just discontinued a different atypical antipsychotic. METHOD: Subjects with
      schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly
      assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention
      Effectiveness (CATIE) investigation were randomly reassigned to double-blind
      treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66];
      quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or
      ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there
      were differences between these four treatments in effectiveness measured by time
      until discontinuation for any reason. RESULTS: The time to treatment
      discontinuation was longer for patients treated with risperidone (median: 7.0
      months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and
      ziprasidone (2.8 months). Among patients who discontinued their previous
      antipsychotic because of inefficacy (N=184), olanzapine was more effective than
      quetiapine and ziprasidone, and risperidone was more effective than quetiapine.
      There were no significant differences between antipsychotics among those who
      discontinued their previous treatment because of intolerability (N=168).
      CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just
      discontinued treatment with an atypical antipsychotic, risperidone and olanzapine
      were more effective than quetiapine and ziprasidone as reflected by longer time
      until discontinuation for any reason.

PMID- 16585436
TI  - Prevalence of dissociative disorders in psychiatric outpatients.
AB  - OBJECTIVE: The purpose of the study was to assess the prevalence of DSM-IV
      dissociative disorders in an inner-city outpatient psychiatric population.
      METHOD: Subjects were 231 consecutive admissions (84 men and 147 women, mean
      age=37 years) to an inner-city, hospital-based outpatient psychiatric clinic. The
      subjects completed self-report measures of dissociation (Dissociative Experiences
      Scale) and trauma history (Traumatic Experiences Questionnaire). Eighty-two
      patients (35%) completed a structured interview for dissociative disorders
      (Dissociative Disorders Interview Schedule). RESULTS: The 82 patients who were
      interviewed did not differ significantly on any demographic measure or on the
      self-report measures of trauma and dissociation from the 149 patients who were
      not interviewed. Twenty-four (29%) of the 82 interviewed patients received a
      diagnosis of a dissociative disorder. Dissociative identity disorder was
      diagnosed in five (6%) patients. Compared to the patients without a dissociative
      disorder diagnosis, patients with a dissociative disorder were significantly more
      likely to report childhood physical abuse (71% versus 27%) and childhood sexual
      abuse (74% versus 29%), but the two groups did not differ significantly on any
      demographic measure, including gender. Chart review revealed that only four (5%)
      patients in whom a dissociative disorder was identified during the study had
      previously received a dissociative disorder diagnosis. CONCLUSIONS: Dissociative
      disorders were highly prevalent in this clinical population and typically had not
      been previously diagnosed clinically. The high prevalence of dissociative
      disorders found in this study may be related to methodological factors (all
      patients were offered an interview rather than only those who had scored high on
      a screening self-report measure) and epidemiological factors (extremely high
      prevalence rates for childhood physical and sexual abuse were present in the
      overall study population).

PMID- 16585437
TI  - Hippocampal and amygdalar volumes in dissociative identity disorder.
AB  - OBJECTIVE: Smaller hippocampal volume has been reported in several stress-related
      psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline
      personality disorder with early abuse, and depression with early abuse. Patients
      with borderline personality disorder and early abuse have also been found to have
      smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes
      in patients with dissociative identity disorder, a disorder that has been
      associated with a history of severe childhood trauma. METHOD: The authors used
      magnetic resonance imaging to measure the volumes of the hippocampus and amygdala
      in 15 female patients with dissociative identity disorder and 23 female subjects
      without dissociative identity disorder or any other psychiatric disorder. The
      volumetric measurements for the two groups were compared. RESULTS: Hippocampal
      volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients
      with dissociative identity disorder, compared to the healthy subjects. The ratio
      of hippocampal volume to amygdalar volume was significantly different between
      groups. CONCLUSIONS: The findings are consistent with the presence of smaller
      hippocampal and amygdalar volumes in patients with dissociative identity
      disorder, compared with healthy subjects.

PMID- 16585438
TI  - Elevated cerebrospinal fluid substance p concentrations in posttraumatic stress
      disorder and major depression.
AB  - OBJECTIVE: The authors tested the hypothesis that concentrations of the pain
      transmitting neuropeptide substance P are elevated in the CSF of patients with
      major depression or posttraumatic stress disorder (PTSD), which have overlapping
      symptoms. The authors also sought to determine if CNS substance P concentrations
      change on provocation of symptoms in PTSD patients. METHOD: The authors measured
      CSF substance P concentrations in medication-free patients with either major
      depression or PTSD and in healthy comparison subjects. Next, using a within
      subject, crossover design, the authors sampled CSF for 6 hours through an
      indwelling subarachnoid catheter in PTSD patients before, during, and after
      exposure to a 60-minute traumatic or neutral videotape stimulus. RESULTS: Both
      depressed and PTSD patients had significantly elevated basal CSF substance P
      concentrations. In the challenge study, marked increases in CSF substance P
      concentrations were found only after precipitation of PTSD symptoms. CSF
      substance P concentrations increased by 169% and 90.6% of baseline levels at 10
      and 70 minutes, respectively, after the start of the traumatic videotape but
      changed by only 1.1% and -8.1% of baseline levels 10 and 70 minutes after the
      start of the neutral videotape. CONCLUSIONS: These results suggest that elevated
      CNS substance P concentrations are involved in both major depression and PTSD.
      The marked increase in CSF substance P concentrations during and after the
      symptom-provoking stimulus, but not after the neutral stimulus, implicates CNS
      release of substance P in the mechanism of acute PTSD symptoms. These data also
      reveal that CNS substance P responds acutely to psychological stress in humans.

PMID- 16585439
TI  - Factors affecting the diagnosis and prediction of PTSD symptomatology in children
      and adolescents.
AB  - OBJECTIVE: In a cohort that spanned all of childhood and suffered equivalent
      types of traumas, the authors examined diagnostic validity and risk factors for
      posttraumatic stress disorder (PTSD). For older children, parent-child agreement
      was investigated. METHOD: Sixty-two children ages 0-18 years who were
      hospitalized with injuries were assessed 2 months later for PTSD. Mothers were
      interviewed, and concurrent interviews were conducted with 24 adolescents.
      RESULTS: Children did not attain the DSM-IV threshold of three criterion C items
      until age 7. The 0-6-year-old group had significantly fewer criterion C symptoms
      (mean=0.43) than the 12-18-year-olds (mean=1.17). The impact of altering
      thresholds for criteria C and D was examined. Older children reported symptoms
      meeting criterion B significantly more often (79.2%) than parents (45.8%).
      Combined parent-child reports yielded significantly more symptoms and higher
      rates for criteria B, C, and D (almost a twofold increase) and for the overall
      diagnosis (37.5%) than parent report alone (4.2%). This 8.9-fold increase in
      diagnosis from combined reports suggests that the diagnostic rates for children
      who cannot make self-reports may greatly underestimate the true numbers. The
      interaction between pretrauma externalizing behavior and witnessing a threat to a
      caregiver had a significant effect on the total number of PTSD symptoms.
      CONCLUSIONS: These findings provide additional support for lowering the
      requirement of three criterion C symptoms for preschool children and raise
      questions about the appropriateness of this threshold for prepubertal children.
      The validity of studies that do not assess symptoms with combined parent and
      child reports is limited.

PMID- 16585440
TI  - Trauma, PTSD, and substance use disorders: findings from the Australian National
      Survey of Mental Health and Well-Being.
AB  - OBJECTIVE: The aim of the present study was to examine the association between
      trauma and posttraumatic stress disorder (PTSD) and substance use disorders and
      to examine the correlates of substance use disorder plus PTSD comorbidity in the
      Australian general population. METHOD: Data were collected from a stratified
      sample of 10,641 participants as part of the Australian National Survey of Mental
      Health and Well-Being. A modified version of the Composite International
      Diagnostic Interview was used to determine the presence of DSM-IV anxiety,
      affective, and substance use disorders and ICD-10 personality disorders. RESULTS:
      Substance use disorder plus PTSD was experienced by a significant minority of the
      Australian general population (0.5%). Among those with PTSD, the most common
      substance use disorder was an alcohol use disorder (24.1%), whereas among those
      with a substance use disorder, PTSD was most common among individuals with an
      opioid use disorder (33.2%). Consistent with U.S. clinical literature,
      individuals with substance use disorder plus PTSD experience significantly poorer
      physical and mental health and greater disability than those with substance use
      disorder alone. In contrast, individuals with PTSD alone and those with substance
      use disorder plus PTSD shared a remarkably similar clinical profile. CONCLUSIONS:
      It is important that individuals entering treatment for substance use disorder or
      PTSD be assessed for this comorbidity. The addition of either disorder may
      present complications that need to be considered for the provision of appropriate
      treatment. Further research is necessary to ascertain which treatments are most
      effective in treating comorbid substance use disorder plus PTSD.

PMID- 16585441
TI  - Trajectories of PTSD: a 20-year longitudinal study.
AB  - OBJECTIVE: This study assessed the psychopathological effects of combat in
      veterans with and without combat stress reaction. METHOD: Veterans (N=214) from
      the 1982 Lebanon War were assessed in a prospective longitudinal design: 131
      suffered from combat stress reaction during the war, and 83 did not. They were
      evaluated 1, 2, 3, and 20 years after the war. RESULTS: Combat stress reaction is
      an important vulnerability marker. Veterans with combat stress reaction were 6.6
      times more likely to endorse posttraumatic stress disorder (PTSD) at all four
      measurements, their PTSD was more severe, and they were at increased risk for
      exacerbation/reactivation. A qualitative analysis of the profile of PTSD symptoms
      revealed some time-related changes in the symptom configuration of veterans who
      did not suffer from combat stress reaction. In both groups, the course
      fluctuated; PTSD rates dropped 3 years postwar and rose again 17 years later; 23%
      of veterans without combat stress reaction reported delayed PTSD. CONCLUSIONS:
      These findings suggest that the detrimental effects of combat are deep and
      enduring and follow a complex course, especially in combat stress reaction
      casualties. The implications of aging and ongoing terror in impeding recovery
      from the psychological wounds of war are discussed.

PMID- 16585442
TI  - Psychological responses to continuous terror: a study of two communities in
      Israel.
AB  - OBJECTIVE: The authors evaluated psychological responses to continuous terror.
      METHOD: Data were collected after 10 months of escalating hostilities against
      civilians in Israel. The study's participants were randomly selected adults
      living in two suburbs of Jerusalem, one frequently and directly exposed to acts
      of terrorism (N=167) and the other indirectly exposed (N=89). Participants
      provided information about exposure to terror-related incidents, disruption of
      daily living, symptoms of posttraumatic stress disorder (PTSD), and general
      distress (assessed with the Brief Symptom Inventory). RESULTS: Residents of the
      directly exposed community reported more frequent exposure to terror and deeper
      disruption of daily living. Notwithstanding, the directly and indirectly exposed
      groups reported comparable rates of PTSD and similar levels of symptoms: 26.95%
      of the directly exposed group and 21.35% of the indirectly exposed group met DSM
      IV PTSD symptom criteria (criteria B through D), and about one-third of those
      with PTSD symptoms (35.7% in the directly exposed group and 31.5% in the
      indirectly exposed group) reported significant distress and dysfunction. Subjects
      who did not meet PTSD symptom criteria had very low levels of PTSD symptoms, and
      their Brief Symptom Inventory scores were within population norms. Exposure and
      disruption of daily living contributed to PTSD symptoms in the directly exposed
      group. Disruption of daily routines contributed to Brief Symptom Inventory scores
      in both groups. CONCLUSIONS: Continuous terror created similar distress in
      proximal and remote communities. Exposure to discrete events was not a necessary
      mediator of terror threat. A subgroup of those exposed developed serious
      symptoms, whereas others were surprisingly resilient. Disruption of daily
      routines was a major secondary stressor.

PMID- 16585443
TI  - Hippocampal volume, PTSD, and alcoholism in combat veterans.
AB  - Studies imposing rigorous control over lifetime alcohol intake have usually not
      found smaller hippocampal volumes in persons with posttraumatic stress disorder.
      Because the majority of negative studies have used adolescent samples, it has
      been suggested that chronicity is a necessary condition for such findings. To
      test the hypothesis that a smaller hippocampus in PTSD is unrelated to comorbid
      alcoholism or to chronicity, this study estimated hippocampal volume in a
      relatively large group (N=99) of combat veterans in which PTSD, lifetime alcohol
      abuse/dependence, and Vietnam versus Gulf War service were crossed. In subjects
      with histories of alcoholism, unadjusted hippocampal volume was 9% smaller in
      persons with PTSD than in those without PTSD. In nonalcoholic subjects, the PTSD
      related difference in hippocampal volume was 3%. The failure to observe a strong
      association between PTSD and hippocampal volume in nonalcoholic subjects was not
      ascribable to younger age, reduced PTSD chronicity, or lower PTSD symptom
      severity. The possibility that smaller hippocampal volume is limited to groups in
      which PTSD is compounded by comorbid alcoholism is not necessarily incompatible
      with results suggesting a smaller hippocampus is predispositional to PTSD.
      Further examination of the role of alcoholism and other comorbid conditions in
      studies of brain structure and function in PTSD appears warranted.

PMID- 16585444
TI  - Natural history of male psychological health, XV: retirement satisfaction.
AB  - OBJECTIVE: Although previous studies of shorter duration have identified numerous
      risks and protective factors that powerfully influence outcomes in young
      adulthood and midlife, this long-term prospective study examines the effect of
      these prognostic factors on age at retirement and satisfaction with retirement.
      METHOD: In this prospective study, a cohort of socially disadvantaged men (N=151)
      were followed from adolescence until a mean age of 75 years (SD=2). Periodic
      interviews, biennial administration of questionnaires, and physical examinations
      every 5 years were conducted to determine biopsychosocial risk variables, age at
      retirement, and satisfaction with retirement. RESULTS: Early age of retirement
      was found to be a function of preexisting mental and physical health and later
      age of retirement a function of occupational status. A surprising finding was
      that risk factors such as poor objective physical health, low income, and
      depression, which are commonly associated with poor outcomes in young adulthood
      and in midlife, were largely unrelated to satisfaction with retirement.
      CONCLUSIONS: A relatively high level of satisfaction with retirement was often
      attained by men who had reported many risk factors for poor child and midlife
      development (e.g., low IQ, dropping out of school, poor mental health, and being
      part of a multiproblem family) but who in later life had some positive resources
      (e.g., a good marriage, a low level neuroticism, enjoyment of vacations, and a
      capacity for play). In short, retirement may offer some men a fresh lease on
      life.

PMID- 16585445
TI  - Diagnosis of comorbid psychiatric disorders in substance users assessed with the
      Psychiatric Research Interview for Substance and Mental Disorders for DSM-IV.
AB  - OBJECTIVE: The authors used the Psychiatric Research Interview for Substance and
      Mental Disorders for DSM-IV (PRISM-IV) to test the reliability of DSM-IV-defined
      disorders, including primary and substance-induced disorders, in substance
      abusing subjects. METHOD: Substance-abusing patients (N=285) from substance
      abuse/dual-diagnosis treatment settings and mental health treatment settings
      participated in test and blind retest interviews with the PRISM-IV, which
      includes specific guidelines for assessment of substance abusers. RESULTS: Kappas
      for primary and substance-induced major depressive disorder ranged from 0.66 to
      0.75. Reliability for psychotic disorders, eating disorders, antisocial
      personality disorder, and borderline personality disorder was in the same range.
      Reliability for most anxiety disorders was lower. Reliability was good to
      excellent (kappas >/=0.65) for most substance dependence disorders. Continuous
      measures (severity, age at onset) had intraclass correlation coefficients >0.70
      with few exceptions. Reliability was better for primary than for substance
      induced disorders, although not greatly so. CONCLUSION: Most DSM-IV psychiatric
      disorders can be assessed in substance-abusing subjects with acceptable to
      excellent reliability by using specifically designed procedures. Good reliability
      improves the likelihood of significant study results.

PMID- 16585446
TI  - Body image and attitudes toward male roles in anabolic-androgenic steroid users.
AB  - OBJECTIVE: The authors sought to expand on previous observations suggesting that
      body-image pathology is associated with illicit use of anabolic-androgenic
      steroids (AAS). In particular, the authors compared current versus past AAS users
      and short-term versus long-term users in this respect. METHOD: The authors
      assessed 89 heterosexual men who lifted weights regularly-48 AAS users and 41
      nonusers-on measures of self-esteem, attitudes toward male roles, body image,
      eating-related attitudes and behaviors, and muscle dysmorphia ("reverse anorexia
      nervosa"). RESULTS: AAS users as a whole showed few differences from nonusers on
      most measures but showed greater symptoms of muscle dysmorphia (e.g., not
      allowing their bodies to be seen in public, giving up pleasurable activities
      because of body-appearance concerns). The current and past AAS users each
      differed only modestly from nonusers on most measures. Short-term AAS
      "experimenters" were also largely indistinguishable from nonusers, but the long
      term AAS users showed striking and significant differences from nonusers on many
      measures, including marked symptoms of muscle dysmorphia and stronger endorsement
      of conventional male roles. CONCLUSIONS: Both body-image pathology and narrow
      stereotypic views of masculinity appear to be prominent among men with long-term
      AAS use. Although our cross-sectional observations cannot confirm that these
      factors help to cause or perpetuate AAS use, a causal hypothesis is certainly
      plausible and deserving of further testing in longitudinal studies. If these
      factors are indeed causal, then AAS users might respond to cognitive behavior
      approaches that simultaneously take aim at both types of maladaptive beliefs.

PMID- 16585447
TI  - Early weaning and hospitalization with alcohol-related diagnoses in adult life.
AB  - OBJECTIVE: This study attempted to determine whether lack of breast-feeding or a
      short duration of breast-feeding during infancy is associated with an elevated
      risk of hospitalization with alcohol-related diagnoses in adult life. METHOD: The
      study was a prospective longitudinal birth cohort design conducted in a sample of
      6,562 men and women, all of whom were born in Copenhagen, Denmark, between
      October 1959 and December 1961. The sample was divided into two categories based
      on duration of breast-feeding, as assessed by a physician interview with mothers
      at a 1-year examination. Psychiatric hospitalizations with alcohol-related
      diagnoses according to ICD-8 or ICD-10 were identified in the Danish Psychiatric
      Central Register in 1999. Nine potential confounders were included as covariates:
      gender of the cohort member, maternal age, parental social status, maternal
      prenatal smoking, unwanted pregnancy, maternal and paternal psychiatric
      hospitalization with alcohol-related diagnosis, and maternal and paternal
      psychiatric hospitalization with other diagnosis. RESULTS: Alcohol-related
      diagnoses were more frequent in men, but the results were comparable for men and
      women. The adjusted predictive effect of early weaning was 1.47. Elevated
      relative risks were also associated with maternal smoking during pregnancy (1.52)
      and unwanted pregnancy status (1.59). Other independent predictors were male
      gender, maternal psychiatric hospitalization with alcohol-related diagnosis, and
      low parental social status. CONCLUSIONS: Independent of a number of other risk
      factors for alcoholism, a significant association between early weaning and
      elevated risk of hospitalization with alcohol-related diagnoses was observed.

PMID- 16585448
TI  - Brain pH response to hyperventilation in panic disorder: preliminary evidence for
      altered acid-base regulation.
AB  - OBJECTIVE: Previous findings of excess brain lactate and delayed end-tidal CO(2)
      (pCO(2)) recovery in subjects with panic disorder during hyperventilation
      suggested altered acid-base regulation. Two models were posited to explain these
      results: 1) subjects with panic disorder demonstrate greater alkalosis to
      hyperventilation, implicating increased lactate as directly compensatory, or 2)
      subjects with panic disorder demonstrate reduced or blunted alkalosis,
      implicating increased lactate as overly compensatory to a normal pH response. In
      both models, delayed pCO(2) recovery in subjects with panic disorder could
      reflect slower pH normalization in the recovery phase. METHOD: Asymptomatic
      medicated patients with panic disorder were studied during regulated
      hyperventilation. Phosphorous spectroscopy was used to measure brain pH every 2
      minutes. Nine subjects with panic disorder were compared to 11 healthy subjects
      at baseline (five scans), during regulated hyperventilation (five scans), and
      across recovery (10 scans). Anxiety symptoms were assessed with standard ratings.
      RESULTS: No subject had a panic attack before hyperventilation. Subjects with
      panic disorder had lower pCO(2) during hyperventilation and slower pCO(2)
      recovery across the posthyperventilation interval. Despite this different
      respiratory response in the panic disorder group, brain pH increases were not
      significantly greater during hyperventilation, nor was pH return to baseline
      slowed during posthyperventilation. A linear regression model derived from data
      of healthy subjects showed pH blunting in the panic disorder group. CONCLUSIONS:
      Although subjects with panic disorder had greater hypocapnea during
      hyperventilation, their observed pH response, not altered from comparison levels,
      implicated exaggerated buffering. It is suggested that increased lactate could
      account for these findings.

PMID- 16585450
TI  - Patient casemix classification for medicare psychiatric prospective payment.
AB  - OBJECTIVE: For a proposed Medicare prospective payment system for inpatient
      psychiatric facility treatment, the authors developed a casemix classification to
      capture differences in patients' real daily resource use. METHOD: Primary data on
      patient characteristics and daily time spent in various activities were collected
      in a survey of 696 patients from 40 inpatient psychiatric facilities. Survey data
      were combined with Medicare claims data to estimate intensity-adjusted daily
      cost. Classification and Regression Trees (CART) analysis of average daily
      routine and ancillary costs yielded several hierarchical classification
      groupings. Regression analysis was used to control for facility and day-of-stay
      effects in order to compare hierarchical models with models based on the recently
      proposed payment system of the Centers for Medicare & Medicaid Services. RESULTS:
      CART analysis identified a small set of patient characteristics strongly
      associated with higher daily costs, including age, psychiatric diagnosis,
      deficits in daily living activities, and detox or ECT use. A parsimonious, 16
      group, fully interactive model that used five major DSM-IV categories and
      stratified by age, illness severity, deficits in daily living activities,
      dangerousness, and use of ECT explained 40% (out of a possible 76%) of daily cost
      variation not attributable to idiosyncratic daily changes within patients. A
      noninteractive model based on diagnosis-related groups, age, and medical
      comorbidity had explanatory power of only 32%. CONCLUSIONS: A regression model
      with 16 casemix groups restricted to using "appropriate" payment variables (i.e.,
      those with clinical face validity and low administrative burden that are easily
      validated and provide proper care incentives) produced more efficient and
      equitable payments than did a noninteractive system based on diagnosis-related
      groups.

PMID- 16585449
TI  - The prevalence and correlates of adult ADHD in the United States: results from
      the National Comorbidity Survey Replication.
AB  - OBJECTIVE: Despite growing interest in adult attention deficit hyperactivity
      disorder (ADHD), little is known about its prevalence or correlates. METHOD: A
      screen for adult ADHD was included in a probability subsample (N=3,199) of 18-44
      year-old respondents in the National Comorbidity Survey Replication, a nationally
      representative household survey that used a lay-administered diagnostic interview
      to assess a wide range of DSM-IV disorders. Blinded clinical follow-up interviews
      of adult ADHD were carried out with 154 respondents, oversampling those with
      positive screen results. Multiple imputation was used to estimate prevalence and
      correlates of clinician-assessed adult ADHD. RESULTS: The estimated prevalence of
      current adult ADHD was 4.4%. Significant correlates included being male,
      previously married, unemployed, and non-Hispanic white. Adult ADHD was highly
      comorbid with many other DSM-IV disorders assessed in the survey and was
      associated with substantial role impairment. The majority of cases were
      untreated, although many individuals had obtained treatment for other comorbid
      mental and substance-related disorders. CONCLUSIONS: Efforts are needed to
      increase the detection and treatment of adult ADHD. Research is needed to
      determine whether effective treatment would reduce the onset, persistence, and
      severity of disorders that co-occur with adult ADHD.

PMID- 16585451
TI  - Psychiatric disorder and separation from military service: a 10-year
      retrospective study.
AB  - OBJECTIVE: This study investigated the association between the onset of
      psychiatric morbidity and separation from military service over a 10-year period
      (1991-2001). METHOD: The prevalence of affective, anxiety, somatic, and substance
      use disorders was assessed in 2,215 male Australian Navy personnel with the
      Composite International Diagnostic Interview. RESULTS: The onset of a psychiatric
      disorder during military service was related to a 19% greater risk of separation
      overall. The majority of those leaving military service did so in the first year
      after symptom onset. Personnel who remained in service past this period had no
      significantly elevated risk of separation in subsequent years. CONCLUSIONS:
      Psychiatric morbidity represents a significant potential cost to defense forces.
      Improved recognition and early management of mental health problems among
      military personnel may improve retention rates.

PMID- 16585452
TI  - Use of FMRI to predict recovery from unipolar depression with cognitive behavior
      therapy.
AB  - OBJECTIVE: In controlled treatment trials, 40%-60% of unmedicated depressed
      individuals respond to cognitive behavior therapy (CBT). The authors examined
      whether pretreatment neural reactivity to emotional stimuli accounted for this
      variation. METHOD: Unmedicated depressed individuals (N=14) and never depressed
      comparison subjects (N=21) underwent fMRI during performance of a task sensitive
      to sustained emotional information processing. Afterward, depressed participants
      completed 16 sessions of CBT. RESULTS: Participants whose sustained reactivity to
      emotional stimuli was low in the subgenual cingulate cortex (Brodmann's area 25)
      and high in the amygdala displayed the strongest improvement with CBT.
      CONCLUSIONS: The presence of emotion regulation disruptions, which are targeted
      in CBT, may be the key to recovery with this intervention.

PMID- 16585453
TI  - Stress responsivity and HPA axis activity in juveniles: results from a home-based
      CO2 inhalation study.
AB  - OBJECTIVE: A previous laboratory-based study found elevated cortisol levels in
      anxious children susceptible to CO(2)-induced panic, but the effects of parent
      diagnosis were not considered. The current home-based study tested the hypothesis
      that parental panic disorder and offspring response to CO(2) are associated with
      elevated cortisol levels in juvenile offspring. METHOD: A total of 131 offspring
      (ages 9-19) of parents with panic disorder, major depression, and no mental
      disorder underwent CO(2) inhalation. Parent and child diagnoses were assessed.
      Salivary cortisol was assayed before and after CO(2) inhalation. RESULTS: Neither
      parents with panic disorder, parents with major depression, or offspring anxiety
      predicted offspring cortisol levels. Independent of parent and child diagnoses,
      anxiety response to CO(2) predicted elevated cortisol levels in offspring.
      CONCLUSIONS: As in adults, anxiety response to CO(2) in juveniles is associated
      with elevated cortisol levels, but elevated cortisol levels are not related to
      parent or child diagnoses.

PMID- 16585454
TI  - Effect of metabotropic glutamate receptor 3 genotype on N-acetylaspartate
      measures in the dorsolateral prefrontal cortex.
AB  - OBJECTIVE: This study was carried out to confirm prior evidence of an effect of a
      single nucleotide polymorphism (SNP) in the metabotropic glutamate receptor 3
      (GRM3) gene (a putative risk factor for schizophrenia) on measures of N
      acetylaspartate in healthy comparison subjects. METHOD: Fifty-four carefully
      screened healthy volunteers genotyped at SNP rs6465084 underwent magnetic
      resonance spectroscopic imaging (MRSI) at 3 T and selected neuropsychological
      testing. RESULTS: The A/A genotype group exhibited a significant reduction of N
      acetylaspartate/creatine levels in the right dorsolateral prefrontal cortex
      compared to the G carriers. A tendency in the same direction was seen in the left
      dorsolateral prefrontal cortex and in the white matter adjacent to the prefrontal
      cortex. CONCLUSIONS: These findings provide further evidence that GRM3 affects
      prefrontal function and that variation in GRM3, monitored by SNP rs6465084,
      affects GRM3 function.

PMID- 16585455
TI  - Time course for antipsychotic treatment response in first-episode schizophrenia.
AB  - OBJECTIVE: The authors examined early onset of antipsychotic action and early
      prediction of nonresponse to antipsychotics in patients with first-episode
      schizophrenia. METHOD: Time to clinical response (>/=20% improvement in total
      score on the Positive and Negative Syndrome Scale [PANSS]) was determined in 522
      participants in a randomized, controlled trial comparing risperidone and
      haloperidol. Median treatment length was 206 days. RESULTS: Clinical response was
      achieved in 77% (N=400) of subjects. Among these patients, clinical response was
      achieved in 23.3%, 23.3%, 18.5%, and 12.5% at weeks 1, 2, 3, and 4, respectively,
      after treatment initiation. However, in 22.5% of patients, response was not
      achieved until after 4 weeks, and in 11.2%, it was not achieved until after 8
      weeks. In 45% of patients, response was achieved with a dose of 1-2 mg/day, in
      27% with 3 mg/day, in 17% with 4 mg/day, and in the remaining 11% with higher
      doses. Improvement in the PANSS total score of at least 30%, 40%, and 50%,
      respectively, were achieved by 63.0%, 44.8%, and 27.5% of patients. CONCLUSIONS:
      Time to antipsychotic response varied widely, suggesting that, in first-episode
      schizophrenia, longer treatment trials may be necessary.

PMID- 16585456
TI  - Classification of somatoform disorders.

PMID- 16585457
TI  - Increasing psychosis in a patient switched from clozaril to generic clozapine.

PMID- 16585458
TI  - Classification of somatoform disorders.

PMID- 16585459
TI  - The psychotherapy of sexually impulsive patients.

PMID- 16585461
TI  - Hallucinations during lamotrigine treatment of bipolar disorder.

PMID- 16585460
TI  - The psychotherapy of sexually impulsive patients.

PMID- 16585463
TI  - Self-portrait after Spanish flu.

PMID- 16585464
TI  - The neural basis of relational memory deficits in schizophrenia.
AB  - CONTEXT: Memory deficits are common in schizophrenia. Recent studies have
      demonstrated that relational memory is particularly impaired. OBJECTIVE: To study
      the neural correlates of relational memory in schizophrenia using functional
      magnetic resonance imaging. DESIGN: Cross-sectional case-control study. SETTING:
      Academic medical center. Subjects Twenty patients with schizophrenia and 17
      control subjects. MAIN OUTCOME MEASURES: Behavioral performance and brain
      activity were assessed during the discrimination of previously seen and novel
      pairs of visual stimuli, which varied in the degree of relational memory load. We
      performed whole-brain and region-of-interest (hippocampus) analyses. RESULTS:
      Schizophrenic subjects displayed normal activation of the presupplementary motor
      area and ventral prefrontal cortex, but significantly decreased recruitment of
      the right parietal cortex and anterior cingulate cortex when discriminating novel
      pairs derived from a sequence of stimuli. Discrimination accuracy was decreased
      in schizophrenia only when the flexible representation of a sequence was
      required. This selective deficit was associated with decreased activation of the
      right parietal cortex and left hippocampus. CONCLUSIONS: Schizophrenia is
      characterized by a specific deficit of relational memory, which is associated
      with impaired function of the parietal cortex and hippocampus. Abnormal
      relational memory may be at the core of 2 prominent features of schizophrenia,
      ie, cognitive deficits and psychosis.

PMID- 16585465
TI  - Variation at the DAOA/G30 locus influences susceptibility to major mood episodes
      but not psychosis in schizophrenia and bipolar disorder.
AB  - CONTEXT: Variation at the DAOA/G30 locus has been described to be associated with
      both schizophrenia and bipolar disorder, but there is little consistency between
      studies of the tested polymorphisms or variants showing association. OBJECTIVES:
      To obtain a stringent replication of association in large samples of both
      disorders using consistent clinical and laboratory methods, and to test the
      hypothesis that association at DAOA/G30 identifies an underlying domain of
      psychopathological abnormalities that cuts across traditional diagnostic
      categories. DESIGN: A systematic study of polymorphisms at DAOA/G30 using genetic
      case-control association analysis. SETTING: Subjects were unrelated and
      ascertained from general psychiatric inpatient and outpatient services.
      PARTICIPANTS: White persons from the United Kingdom meeting criteria for DSM-IV
      schizophrenia (n = 709) or bipolar I disorder (n = 706) and 1416 ethnically
      matched controls. METHODS: Nine polymorphisms that tag common genetic variations
      at DAOA/G30 were genotyped in all of the individuals, and comparisons were made
      between affected and unaffected individuals. RESULTS: We identified significant
      association (P = .01-.047) between 3 single-nucleotide polymorphisms and bipolar
      disorder but failed to find association with schizophrenia. Analyses across the
      traditional diagnostic categories revealed significant evidence (P = .002-.02)
      for association with 4 single-nucleotide polymorphisms in the subset of cases (n
      = 818) in which episodes of major mood disorder had occurred (gene-wide P =
      .009). We found a similar pattern of association in bipolar cases and in
      schizophrenia cases in which individuals had experienced major mood disorder. In
      contrast, we found no evidence for association in the subset of cases (n = 1153)
      in which psychotic features occurred (all P>.08). CONCLUSIONS: Despite being
      originally described as a schizophrenia susceptibility locus, our data suggest
      that variation at the DAOA/G30 locus does not primarily increase susceptibility
      for prototypical schizophrenia or psychosis. Instead, our results imply that
      variation at the DAOA/G30 locus influences susceptibility to episodes of mood
      disorder across the traditional bipolar and schizophrenia categories.

PMID- 16585466
TI  - Associations of hormones and menopausal status with depressed mood in women with
      no history of depression.
AB  - CONTEXT: Whether depressed mood reported in the transition to menopause by women
      with no history of depression is associated with menopausal status and changes in
      reproductive hormones is controversial and lacks scientific information.
      OBJECTIVES: To identify new onset of depressive symptoms and diagnosed depressive
      disorders in the menopausal transition and to determine the associations of
      menopausal status, reproductive hormones, and other risk factors with these
      cases. DESIGN: A within-woman, longitudinal (8-year) study to identify risk
      factors of depressed mood. SETTING: A subset of a randomly identified, population
      based cohort. PARTICIPANTS: Premenopausal women with no history of depression at
      cohort enrollment. MAIN OUTCOME MEASURES: The Center for Epidemiological Studies
      of Depression scale (CES-D) was used to assess depressive symptoms, and the
      Primary Care Evaluation of Mental Disorders (PRIME-MD) was used to identify
      clinical diagnoses of depressive disorders. RESULTS: High CES-D scores (> or=16)
      were more than 4 times more likely to occur during a woman's menopausal
      transition compared with when she was premenopausal (odds ratio, 4.29; 95%
      confidence interval, 2.39-7.72; P<.001). Within-woman change in menopausal
      status, increased levels of follicle-stimulating hormone and luteinizing hormone,
      and increased variability of estradiol, follicle-stimulating hormone, and
      luteinizing hormone around the woman's own mean levels were each significantly
      associated with high CES-D scores after adjusting for smoking, body mass index,
      premenstrual syndrome, hot flashes, poor sleep, health status, employment, and
      marital status. A diagnosis of depressive disorder was 2(1/2) times more likely
      to occur in the menopausal transition compared with when the woman was
      premenopausal (odds ratio, 2.50; 95% confidence interval, 1.25-5.02; P=.01); the
      hormone measures were also significantly associated with this outcome.
      CONCLUSION: Transition to menopause and its changing hormonal milieu are strongly
      associated with new onset of depressed mood among women with no history of
      depression.

PMID- 16585467
TI  - Risk for new onset of depression during the menopausal transition: the Harvard
      study of moods and cycles.
AB  - CONTEXT: Transition to menopause has long been considered a period of increased
      risk for depressive symptoms. However, it is unclear whether this period is one
      of increased risk for major depressive disorder, particularly for women who have
      not had a previous episode of depression. OBJECTIVE: To examine the association
      between the menopausal transition and onset of first lifetime episode of
      depression among women with no history of mood disturbance. DESIGN: Longitudinal,
      prospective cohort study. SETTING: A population-based cross-sectional sample.
      PARTICIPANTS: Premenopausal women, 36 to 45 years of age, with no lifetime
      diagnosis of major depression (N = 460), residing in 7 Boston, Mass, metropolitan
      area communities. Main Outcome Measure Incidence of new onset of depression based
      on structured clinical interviews, Center for Epidemiologic Studies Depression
      Scale scores, and an operational construct for depression. RESULTS: Premenopausal
      women with no lifetime history of major depression who entered the perimenopause
      were twice as likely to develop significant depressive symptoms as women who
      remained premenopausal, after adjustment for age at study enrollment and history
      of negative life events. The increased risk for depression was somewhat greater
      in women with self-reported vasomotor symptoms. CONCLUSIONS: The current study
      suggests that within a similarly aged population of women with no lifetime
      history of depression, those who enter the menopausal transition earlier have a
      significant risk for first onset of depression. Further studies are needed to
      determine more definitively whether other factors, such as the presence of
      vasomotor symptoms, use of hormone therapy, and the occurrence of adverse life
      events, independently modify this risk. Physical symptoms associated with the
      menopausal transition and mood changes seen during this period may affect many
      women as they age and may lead to a significant burden of illness.

PMID- 16585468
TI  - Behavioral depression and positron emission tomography-determined serotonin 1A
      receptor binding potential in cynomolgus monkeys.
AB  - CONTEXT: Current animal models of depression are inadequate to further our
      understanding of depression. New models that allow for analysis of cognitive
      function and sex differences are needed. OBJECTIVE: To characterize serotonin 1A
      (5-HT(1A)) receptor binding potential (BP) and its relationship with specific
      characteristics of behavioral depression in cynomolgus monkeys. DESIGN: A 23
      month case-control study. SETTING: Small social groups in the laboratory.
      Subjects Seventeen adult female cynomolgus monkeys. MAIN OUTCOME MEASURES:
      Serotonin 1A receptor BP was examined by positron emission tomography using the
      radioligand 4,2"-(methoxyphenyl)-1-[2"-(N-2"-pyridinyl)-p
      fluorobenzamido]ethylpiperazine in the raphe, amygdala, hippocampus, and anterior
      cingulate cortex in monkeys characterized by behavioral observation as depressed
      or not depressed. Aggression, submission, affiliation, pathologic behaviors, and
      activity levels were determined by behavioral observation. Heart rate and
      hypothalamic-pituitary-adrenal function were also determined. RESULTS: Throughout
      the brain areas examined, there was a reduction in 5-HT(1A) BP in depressed
      monkeys. The 5-HT(1A) BP in the amygdala and hippocampus was associated with
      aggression and submission. Friendly interaction, grooming, and locomotion were
      associated with 5-HT(1A) BP in the left cingulate cortex, whereas attention
      directed toward the environment was associated with 5-HT(1A) BP in the right
      cingulate cortex. The 5-HT(1A) receptor BP was inversely associated with heart
      rate in the raphe, left cingulate, and right amygdala. CONCLUSIONS: This is the
      fourth in a series of studies that suggest that depressive behavior in adult
      female cynomolgus monkeys is similar to that observed in humans. It has been
      observed in 2 large groups of monkeys randomly selected from feral populations,
      suggesting that the capacity for depression is inherent in the species. This
      animal model holds promise to further our understanding of the basic mechanisms
      of affective behavior, the neuropathophysiologic characteristics of depression
      and the cognitive dysfunction that accompanies them, genetic and environmental
      factors that may affect depression risk, and the role of reproductive function in
      the excess depression risk in women.

PMID- 16585469
TI  - Gender disadvantage and reproductive health risk factors for common mental
      disorders in women: a community survey in India.
AB  - BACKGROUND: Gender disadvantage and reproductive health are major determinants of
      women's health in developing countries. OBJECTIVE: To determine the association
      of factors indicative of gender disadvantage and reproductive health with the
      risk of common mental disorders (CMDs) in women. DESIGN: Cross-sectional survey
      from November 1, 2001, to June 15, 2003. PARTICIPANTS: A total of 3000 women
      randomly selected from a sampling frame of women aged 18 to 45 years in Goa; 2494
      women participated. MAIN OUTCOME MEASURES: The primary outcome was the presence
      of a CMD, as defined by the Revised Clinical Interview Schedule. An interview and
      blood and vaginal/urine specimens were collected to ascertain risk factors.
      RESULTS: The prevalence of CMD was 6.6% (95% confidence interval [CI], 5.7%
      7.6%). Mixed anxiety-depressive disorder was the most common diagnosis (64.8%).
      Factors independently associated with the risk for CMD were factors indicative of
      gender disadvantage, particularly sexual violence by the husband (odds ratio
      [OR], 2.3; 95% CI, 1.1-4.6), being widowed or separated (OR, 5.4; 95% CI, 1.0
      30.0), having low autonomy in decision making (OR, 1.98; 95% CI, 1.2-3.2), and
      having low levels of support from one's family (OR, 2.2; 95% CI, 1.4-3.3);
      reproductive health factors, particularly gynecological complaints such as
      vaginal discharge (OR, 3.2; 95% CI, 2.2-4.8) and dyspareunia (OR, 2.5; 95% CI,
      1.4-4.6); and factors indicative of severe economic difficulties, such as hunger
      (OR, 2.7; 95% CI, 1.6-4.6). There was no association between biological
      indicators (anemia and reproductive tract infections) and CMD. CONCLUSIONS: The
      clinical assessment of CMD in women must include exploration of violence and
      gender disadvantage. Gynecological symptoms may be somatic equivalents of CMD in
      women in Asian cultures.

PMID- 16585471
TI  - The epidemiology of panic attacks, panic disorder, and agoraphobia in the
      National Comorbidity Survey Replication.
AB  - CONTEXT: Only limited information exists about the epidemiology of DSM-IV panic
      attacks (PAs) and panic disorder (PD). OBJECTIVE: To present nationally
      representative data about the epidemiology of PAs and PD with or without
      agoraphobia (AG) on the basis of the US National Comorbidity Survey Replication
      findings. DESIGN AND SETTING: Nationally representative face-to-face household
      survey conducted using the fully structured World Health Organization Composite
      International Diagnostic Interview. PARTICIPANTS: English-speaking respondents
      (N=9282) 18 years or older. MAIN OUTCOME MEASURES: Respondents who met DSM-IV
      lifetime criteria for PAs and PD with and without AG. RESULTS: Lifetime
      prevalence estimates are 22.7% for isolated panic without AG (PA only), 0.8% for
      PA with AG without PD (PA-AG), 3.7% for PD without AG (PD only), and 1.1% for PD
      with AG (PD-AG). Persistence, lifetime number of attacks, and number of years
      with attacks increase monotonically across these 4 subgroups. All 4 subgroups are
      significantly comorbid with other lifetime DSM-IV disorders, with the highest
      odds for PD-AG and the lowest for PA only. Scores on the Panic Disorder Severity
      Scale are also highest for PD-AG (86.3% moderate or severe) and lowest for PA
      only (6.7% moderate or severe). Agoraphobia is associated with substantial
      severity, impairment, and comorbidity. Lifetime treatment is high (from 96.1% for
      PD-AG to 61.1% for PA only), but 12-month treatment meeting published treatment
      guidelines is low (from 54.9% for PD-AG to 18.2% for PA only). CONCLUSION:
      Although the major societal burden of panic is caused by PD and PA-AG, isolated
      PAs also have high prevalence and meaningful role impairment.

PMID- 16585473
TI  - Effect of team sport participation on genetic predisposition to adolescent
      smoking progression.
AB  - CONTEXT: There is much to be learned about why some adolescents progress to a
      regular smoking habit and others do not. OBJECTIVE: To evaluate whether (1) team
      sport participation buffers the effect of having 2 smoking risk genotypes (the
      dopamine reuptake transporter [SLC6A3] and the dopamine D(2) receptor [DRD2]) or
      1 of these risk genotypes vs having none on adolescent smoking progression and
      (2) the buffering effects of team sports were due to physical activity associated
      with team sport participation. DESIGN: Longitudinal cohort study. Survey data
      were collected annually from grade 9 to the end of grade 12. Self-report measures
      included smoking, team sport participation, physical activity, depression,
      smoking exposure, and alcohol and marijuana use. DNA was collected via buccal
      swabs. Data were analyzed using latent growth modeling. SETTING: Five public high
      schools in Virginia. PARTICIPANTS: A total of 361 students of European ancestry.
      Main Outcome Measure Smoking progression. RESULTS: For adolescents participating
      in at least 1 team sport, but not for adolescents with no team sport
      participation, physical activity had a significant negative effect on smoking
      progression (z = -3.85, P<.001; chi(2)(1,N = 361) = 6.73, P = .009). In addition,
      having 1 (z = 2.69; P = .007) and 2 (z = 2.22; P = .03) smoking risk genotypes
      had a positive effect on physical activity. These represented significant between
      group effects (chi(2)(1,N = 361) = 6.29, P = .01; chi(2)(1,N = 361) = 3.81, P =
      .05, respectively). Thus, having 1 or more smoking risk genotypes was related to
      higher levels of physical activity, which, in turn, was related to lower levels
      of smoking progression for adolescents participating in at least 1 team sport but
      not for adolescents with no team sport participation. CONCLUSIONS: This study
      provides the first evidence of an interaction between environmental influences
      and specific genes on adolescent smoking and may promote an understanding of
      important protective relationships in the environment.

PMID- 16585472
TI  - A randomized clinical trial of a new behavioral treatment for drug abuse in
      people with severe and persistent mental illness.
AB  - CONTEXT: Drug abuse by people with severe mental disorder is a significant public
      health problem for which there is no empirically validated treatment. OBJECTIVE:
      To evaluate the efficacy of a new behavioral treatment for drug abuse in this
      population: Behavioral Treatment for Substance Abuse in Severe and Persistent
      Mental Illness (BTSAS). DESIGN: Participants were randomly assigned to 6 months
      of treatment in either BTSAS or a manualized control condition: Supportive
      Treatment for Addiction Recovery (STAR). SETTING: Treatment was conducted in
      community-based outpatient clinics and a Veterans Affairs medical center in
      Baltimore, Md. PARTICIPANTS: Participants were 129 stabilized outpatients meeting
      DSM criteria for drug dependence (cocaine, heroin, or cannabis) and serious
      mental illness: 39.5% met DSM-IV criteria for schizophrenia or schizoaffective
      disorder; 55.8%, for major affective disorders; and the remainder met criteria
      for severe and persistent mental illness and other Axis I disorders.
      INTERVENTIONS: Both treatments were administered by trained health care
      professionals in small groups, twice a week for 6 months. The BTSAS program is a
      social learning intervention that includes motivational interviewing, a
      urinalysis contingency, and social skills training. The control condition, STAR,
      is a supportive group discussion treatment. Main Outcome Measure The primary
      outcome measure was urinalysis results from twice-weekly treatment sessions.
      RESULTS: The BTSAS program was significantly more effective than STAR in
      percentage of clean urine test results, survival in treatment, and attendance at
      sessions. The BTSAS program also had significant effects on important community
      functioning variables, including hospitalization; money available for living
      expenses; and quality of life. CONCLUSIONS: The BTSAS program is an efficacious
      treatment. Further work needs to be done to increase the proportion of eligible
      patients who are able to become engaged in treatment.

PMID- 16585474
TI  - Perceived loss of memory ability and cerebral metabolic decline in persons with
      the apolipoprotein E-IV genetic risk for Alzheimer disease.
AB  - CONTEXT: Concerns about age-related memory loss are greater in persons who have
      the apolipoprotein E-IV (APOE4) genetic risk for Alzheimer disease, but the
      correlation between the degree of concerns and future cerebral metabolic decline
      is unknown. OBJECTIVE: To investigate whether the degree of self-perceived memory
      loss is associated with regional cerebral metabolic decline. DESIGN: Longitudinal
      study. SETTING: Aging and Memory Research Center, Semel Institute for
      Neuroscience and Human Behavior, University of California, Los Angeles.
      PARTICIPANTS: Thirty right-handed, cognitively intact, middle-aged and older
      adults (age range, 50-82 years) with age-associated memory complaints, 14 of whom
      were carriers of the apolipoprotein E-IV allele, were recruited for longitudinal
      study. MAIN OUTCOME MEASURES: At baseline, we administered a standardized
      neuropsychological battery and assessed self-appraisal of memory functioning
      using the Memory Functioning Questionnaire, which yields 4 factor scores
      indicating frequency of forgetting, seriousness of forgetting, retrospective
      functioning, and mnemonics use. Regional cerebral glucose metabolism was
      determined using fluorodeoxyglucose F18-positron emission tomography at baseline
      and after 2 years. RESULTS: At baseline, APOE4 carriers and noncarriers did not
      differ significantly on objective memory measures or on Memory Functioning
      Questionnaire factor scores. However, the factor score for frequency of
      forgetting significantly correlated with global cerebral metabolic decline in all
      subjects regardless of APOE4 genetic risk (P = .01). By contrast, the factor
      score for mnemonics use significantly correlated with metabolic decline in the
      temporal regions in APOE4 carriers but not in noncarriers (P = .03). CONCLUSIONS:
      The degree of perceived memory loss correlates with subsequent global cerebral
      metabolic decline for APOE4 carriers and noncarriers; hence, memory complaints
      may reflect underlying cerebral metabolic changes. Compensatory strategies, as
      reflected by more frequent mnemonics use in APOE4 carriers, may reflect
      underlying metabolic changes in the brain regions associated with prodromal
      Alzheimer disease. Self-reported mnemonics use may be helpful in identifying
      persons for clinical monitoring.

PMID- 16585475
TI  - Monoamines and neurosteroids in sexual function during induced hypogonadism in
      healthy men.
AB  - CONTEXT: Although the behavioral effects of high-dose androgen administration may
      involve alterations in serotonergic activity, few studies have investigated the
      impact of androgen withdrawal on the central nervous system in humans. OBJECTIVE:
      To examine the effects of pharmacologically induced hypogonadism on several
      cerebrospinal fluid (CSF) systems that could mediate the behavioral concomitants
      of hypogonadism. DESIGN: Double-blind assessment of the effects of the short-term
      induction of hypogonadism and subsequent replacement with testosterone and
      placebo in a crossover design. SETTING: National Institutes of Health, Bethesda,
      Md. PARTICIPANTS: Twelve healthy male volunteers. INTERVENTIONS: We administered
      the gonadotropin-releasing hormone agonist leuprolide acetate (7.5 mg
      intramuscularly every 4 weeks) to the healthy male volunteers, creating a
      hypogonadal state, and then either replaced testosterone (200 mg intramuscularly)
      or administered a placebo every 2 weeks for 1 month. MAIN OUTCOME MEASURES: Mood
      and behavioral symptoms were monitored with daily self-ratings, and lumbar
      punctures were performed during both hypogonadal (placebo) and testosterone
      replaced conditions for CSF levels of steroids and monoamine metabolites.
      RESULTS: The CSF testosterone, dihydrotestosterone, and androsterone levels were
      significantly lower during hypogonadism (P=.002, .04, and .046, respectively),
      but no significant changes were observed in CSF measures of 5-hydroxyindoleacetic
      acid, homovanillic acid, dehydroepiandrosterone, or pregnenolone. Decreased
      sexual interest was observed during the hypogonadal state compared with both
      baseline and testosterone replacement (P=.009) and correlated significantly with
      CSF measures of androsterone during both hypogonadism and testosterone
      replacement (r = -0.76 and -0.81, respectively; P<.01). Moreover, the change in
      severity of decreased sexual interest correlated significantly with the change in
      CSF androsterone levels between testosterone replacement and hypogonadism (r = 
      0.68; P<.05). The CSF 5-hydroxyindoleacetic acid and homovanillic acid levels did
      not correlate significantly with any behavioral or CSF measure. CONCLUSION: These
      data suggest that the neurosteroid androsterone contributes to the regulation of
      sexual function in men.

PMID- 16585476
TI  - Prediction of heterogeneity in intelligence and adult prognosis by genetic
      polymorphisms in the dopamine system among children with attention
      deficit/hyperactivity disorder: evidence from 2 birth cohorts.
AB  - CONTEXT: The study and treatment of psychiatric disorders is made difficult by
      the fact that patients with identical symptoms often differ markedly in their
      clinical features and presumably in their etiology. A principal aim of genetic
      research is to provide new information that can resolve such clinical
      heterogeneity and that can be incorporated into diagnostic practice. OBJECTIVE:
      To test the hypothesis that the DRD4 seven-repeat allele and DAT1 ten-repeat
      allele would prove useful in identifying a subset of children with attention
      deficit/hyperactivity disorder (ADHD) who have compromised intellectual
      functions. DESIGN: Longitudinal epidemiologic investigation of 2 independent
      birth cohorts. SETTING: Britain and New Zealand. PARTICIPANTS: The first cohort
      was born in Britain in 1994-1995 and includes 2232 children; the second cohort
      was born in New Zealand in 1972-1973 and includes 1037 children. MAIN OUTCOME
      MEASURES: Evaluation of ADHD, IQ, and adult psychosocial adjustment. RESULTS: We
      present replicated evidence that polymorphisms in the DRD4 and DAT1 genes were
      associated with variation in intellectual functioning among children diagnosed as
      having ADHD, apart from severity of their symptoms. We further show longitudinal
      evidence that these polymorphisms predicted which children with ADHD were at
      greatest risk for poor adult prognosis. CONCLUSION: The findings indicate that
      genetic information of this nature may prove useful for etiology-based
      psychiatric nosologies.

PMID- 16585477
TI  - Effects of media violence on health-related outcomes among young men.
AB  - OBJECTIVE: To test the effects of media violence exposure on blood pressure,
      negative affect, hostile social information processing, uncooperative behavior,
      and attitudes toward health risk behaviors among young men varying in lifetime
      violence exposure within the home and community. DESIGN: Experimental laboratory
      study. SETTING: University campus situated within an urban environment.
      PARTICIPANTS: One hundred male undergraduates aged 18 to 21 years. INTERVENTION:
      Men who had previously reported differing amounts of lifetime home and community
      violence were randomly assigned to play The Simpsons: Hit and Run (low-violence
      condition) or Grand Theft Auto III (high-violence condition). MAIN OUTCOME
      MEASURES: Systolic and diastolic blood pressure; negative affect; hostile social
      information processing; uncooperative behavior; and permissive attitudes toward
      violence, alcohol use, marijuana use, and sexual activity without condom use.
      RESULTS: Men randomly assigned to play Grand Theft Auto III exhibited greater
      increases in diastolic blood pressure from a baseline rest period to game play,
      greater negative affect, more permissive attitudes toward using alcohol and
      marijuana, and more uncooperative behavior in comparison with men randomly
      assigned to play The Simpsons. Only among participants with greater exposure to
      home and community violence, play of Grand Theft Auto III led to elevated
      systolic blood pressure in comparison with play of The Simpsons (mean, 13 vs 5 mm
      Hg). CONCLUSIONS: Media violence exposure may play a role in the development of
      negative attitudes and behaviors related to health. Although youth growing up in
      violent homes and communities may become more physiologically aroused by media
      violence exposure, all youth appear to be at risk for potentially negative
      outcomes.

PMID- 16585478
TI  - Short-term and long-term effects of violent media on aggression in children and
      adults.
AB  - OBJECTIVES: To test whether the results of the accumulated studies on media
      violence and aggressive behavior are consistent with the theories that have
      evolved to explain the effects. We tested for the existence of both short-term
      and long-term effects for aggressive behavior. We also tested the theory-driven
      hypothesis that short-term effects should be greater for adults and long-term
      effects should be greater for children. DESIGN: Meta-analysis. PARTICIPANTS:
      Children younger than 18 years and adults. MAIN EXPOSURES: Violent media,
      including TV, movies, video games, music, and comic books. MAIN OUTCOME MEASURES:
      Measures of aggressive behavior, aggressive thoughts, angry feelings,
      physiological arousal (eg, heart rate, blood pressure), and helping behavior.
      RESULTS: Effect size estimates were combined using meta-analytic procedures. As
      expected, the short-term effects of violent media were greater for adults than
      for children whereas the long-term effects were greater for children than for
      adults. The results also showed that there were overall modest but significant
      effect sizes for exposure to media violence on aggressive behaviors, aggressive
      thoughts, angry feelings, arousal levels, and helping behavior. CONCLUSIONS: The
      results are consistent with the theory that short-term effects are mostly due to
      the priming of existing well-encoded scripts, schemas, or beliefs, which adults
      have had more time to encode. In contrast, long-term effects require the learning
      (encoding) of scripts, schemas, or beliefs. Children can encode new scripts,
      schemas, and beliefs via observational learning with less interference and effort
      than adults.

PMID- 16585479
TI  - Disentangling the relation between television viewing and cognitive processes in
      children with attention-deficit/hyperactivity disorder and comparison children.
AB  - OBJECTIVES: To develop causal hypotheses regarding the effects of television
      viewing on cognitive processes in children and to examine the proposition that
      deleterious effects of television may be stronger among children with attention
      deficit/hyperactivity disorder. DESIGN: Longitudinal study involving 2 phases
      occurring 18 months apart. SETTING: University research facilities in Lexington.
      PARTICIPANTS: Fifty-nine children with attention-deficit/hyperactivity disorder
      and 106 comparison children. The children's mean age was 7.18 years at phase 1
      and 8.74 years at phase 2. MAIN OUTCOME MEASURES: Laboratory measures of visual
      attention to television, cognitive engagement to televised stories, factual
      recall of televised stories, and causal recall of televised stories. Parental
      reports of a child's weekly television viewing. RESULTS: Among comparison
      children, phase 1 television viewing negatively predicted phase 2 visual
      attention and phase 2 cognitive engagement (after accounting for phase 1 levels
      of the outcome variables and any relevant demographic variables). Also among
      comparison children, phase 1 attention negatively predicted phase 2 television
      viewing, even after accounting for phase 1 levels of television viewing and
      relevant demographic variables. These patterns were not observed among children
      with attention-deficit/hyperactivity disorder. CONCLUSIONS: Contrary to recent
      arguments, television viewing was associated with cognitive abilities in
      comparison children but not children with attention-deficit/hyperactivity
      disorder, a finding that suggests more careful examinations of the relation
      between television viewing and children's cognitive abilities are in order.
      Future studies should consider the possibility that any effects of television may
      be limited to certain developmental periods.

PMID- 16585480
TI  - Does children's screen time predict requests for advertised products? Cross
      sectional and prospective analyses.
AB  - OBJECTIVE: To examine children's screen media exposure and requests for
      advertised toys and food/drinks. DESIGN: Prospective cohort study. SETTING:
      Twelve elementary schools in northern California. PARTICIPANTS: Eight hundred
      twenty-seven third grade children participated at baseline; 386 students in 6
      schools were followed up for 20 months. INTERVENTION: None. MAIN OUTCOME
      MEASURES: Child self-reported requests for advertised toys and foods/drinks.
      RESULTS: At baseline, children's screen media time was significantly associated
      with concurrent requests for advertised toys (Spearman r = 0.15 [TV viewing] and
      r = 0.20 [total screen time]; both P<.001) and foods/drinks (Spearman r = 0.16
      [TV viewing] and r = 0.18 [total screen time]; both P<.001). In prospective
      analysis, children's screen media time at baseline was significantly associated
      with their mean number of toy requests 7 to 20 months later (Spearman r = 0.21
      [TV viewing] and r = 0.24 [total screen time]; both P<.001) and foods/drinks
      requests (Spearman r = 0.14 [TV viewing] and r = 0.16 [total screen time]; both
      P<.01). After adjusting for baseline requests and sociodemographic variables, the
      relationship between screen media exposure and future requests for advertised
      foods/drinks remained significant for total TV viewing and total screen media
      exposure. The relationship with future requests for toys remained significant for
      total screen media exposure. CONCLUSIONS: Screen media exposure is a prospective
      risk factor for children's requests for advertised products. Future experimental
      studies on children's health- and consumer-related outcomes are warranted.

PMID- 16585483
TI  - Social interactions in adolescent television viewing.
AB  - OBJECTIVE: To examine whether social interactions influence the television
      viewing choices of adolescents in grades 7 through 12. DESIGN: Data from a
      nationally representative cross-sectional survey were used to examine the
      association between individual-level and school-level television choices. An
      instrumental variables approach was used to solve the simultaneity problem found
      in models that examine the association between individual and aggregate choices.
      SETTING: In-home interviews in the United States collected in 1996. PARTICIPANTS:
      A sample of 4532 students in grades 7 through 12 in 132 US public and private
      schools who participated in the National Longitudinal Study of Adolescent Health
      (Add Health). MAIN EXPOSURE: The reported television viewing choices of an
      individual's schoolmates. MAIN OUTCOME MEASURE: The number of hours of television
      individuals reported viewing in a week. RESULTS: The number of hours of
      television that adolescents report viewing per week was associated with their
      peers' reported hours of television viewing. Adjusted for other covariates, a 1
      hour increase in average school-level television viewing was associated with an
      increase in almost half an hour of television viewing at the individual level.
      CONCLUSIONS: Evidence suggests that social interactions within schools influence
      the hours of television that adolescents report viewing. This finding is
      important for both future attempts at modeling the determinants of adolescent
      television viewing and suggestions for future policy interventions. The presence
      of social interactions implies that interventions that affect the social norms of
      television viewing within schools could also change individual television
      viewing. In reducing the number of hours of television watched, these
      interventions could also positively affect adolescent obesity, emotional
      problems, and academic achievement.

PMID- 16585481
TI  - Development and validation of a smoking media literacy scale for adolescents.
AB  - OBJECTIVES: To develop a smoking media literacy (SML) scale by using empiric
      survey data from a large sample of high school students and to assess reliability
      and criterion validity of the scale. DESIGN: On the basis of an established
      theoretical framework, 120 potential items were generated, and items were
      eliminated or altered on the basis of input from experts and students. Cross
      sectional responses to scale items, demographics, smoking-related variables, and
      multiple covariates were obtained to refine the scale and determine its
      reliability and validity. SETTING: One large Pittsburgh, Pa, high school.
      PARTICIPANTS: A total of 1211 high school students aged 14 to 18 years. MAIN
      OUTCOME MEASURES: Current smoking, susceptibility to smoking, attitudes toward
      smoking, and smoking norms. RESULTS: Factor analysis demonstrated a strong 1
      factor scale with 18 items (alpha = 0.87). After controlling for all covariate
      data, SML had a statistically significant and independent association with
      current smoking (P = .01), susceptibility (P<.001), and attitudes (P<.001), but
      not norms (P = .42). Controlling for all covariates, an increase of 1 point on
      the 10-point SML scale was associated with a 22% decrease in the odds of being a
      smoker and a 31% decrease in the odds of being susceptible to smoking.
      CONCLUSIONS: Smoking media literacy can be measured with excellent reliability
      and concurrent criterion validity. Given the independent association between SML
      and smoking, media literacy may be a promising tool for future tobacco control
      interventions.

PMID- 16585482
TI  - Television viewing and risk of sexual initiation by young adolescents.
AB  - OBJECTIVE: To determine if television viewing is associated with the risk of
      initiating sexual intercourse in young adolescents. DESIGN: Secondary analysis of
      data obtained from 1994 through 1996. SETTING: The National Longitudinal Study of
      Adolescent Health. PARTICIPANTS: The 4808 students younger than 16 years who had
      not initiated intercourse before baseline interview. EXPOSURES: Primary exposure
      was self-reported daily television watching, categorized as low (< 2 hours) or
      high (> or =2 hours) use. Secondary exposure was parental regulation of
      television programming watched. MAIN OUTCOME MEASURE: Odds ratio for initiating
      intercourse by 1-year follow-up, adjusted for potential confounders. RESULTS: At
      baseline, 2414 (48.8%) subjects watched television 2 or more hours per day. By 1
      year follow-up, 791 (15.6%) subjects had initiated intercourse. Sexual initiation
      was associated with high television use (adjusted odds ratio, 1.35; 95%
      confidence interval, 1.01-1.79) and lack of parental regulation of television
      programming (adjusted odds ratio, 1.35; 95% confidence interval, 1.01-1.80). Most
      subjects (73.8%) reported strong parental disapproval of sex; their overall rate
      of initiation was 12.5%, and their risk was independently associated with high
      television use (adjusted odds ratio, 1.72; 95% confidence interval, 1.24-2.40)
      and lack of parental regulation of television programming (adjusted odds ratio,
      1.35; 95% confidence interval, 1.01-1.81). Among adolescents who did not report
      strong parental disapproval, the rate of sexual initiation was higher (24.1%) but
      unrelated to television use. CONCLUSION: Among young adolescents who reported
      strong parental disapproval of sex, watching television 2 or more hours per day
      and lack of parental regulation of television programming were each associated
      with increased risk of initiating sexual intercourse within a year.

PMID- 16585484
TI  - Is television viewing associated with social isolation? Roles of exposure time,
      viewing context, and violent content.
AB  - OBJECTIVE: To estimate associations between children's peer integration and
      amount of time they spend (1) watching television, (2) watching violent
      television, and (3) co-viewing television with friends. DESIGN: Survey using
      nationally representative data from the Panel Study of Income Dynamics-Child
      Development Supplement Wave 1. SETTING: Nationwide survey of families with young
      children performed in 1997. PARTICIPANTS: Of 3562 children, 1356 had sufficient
      data for inclusion in analyses (563 children aged 6 to 8 years and 793 children
      aged 9 to 12 years). MAIN EXPOSURE: Total time viewing television, with and
      without friends present, and time viewing violent and nonviolent television
      content. MAIN OUTCOME MEASURE: Amount of time children spent with friends as
      reported in two 24-hour activity diaries. RESULTS: Viewing violent programs (but
      not nonviolent programs) was negatively related to time children spent with
      friends (aged 6-8 years, unstandardized regression coefficient [beta] = - 0.34,
      95% confidence interval [CI], - 0.59 to - 0.08; aged 9-12 years, beta = - 0.41,
      95% CI, - 0.65 to - 0.18). More time viewing television with friends was
      associated with more time engaging in other activities with friends (aged 6-8
      years, beta = 0.98, 95% CI, 0.61 to 1.36; aged 9-12 years, beta = 1.03, 95% CI,
      0.72 to 1.34). CONCLUSIONS: The more time that children spent viewing violent
      programs, the less time they spent with their friends. While this study cannot
      determine the direction of effects for this relationship, a cyclical process
      between violent media and peer integration best explains the findings. To
      optimize social development and mental health, children's access to violent media
      should be limited.

PMID- 16585485
TI  - Parental media mediation styles for children aged 2 to 11 years.
AB  - BACKGROUND: Studies indicate that children use media (television, video, and
      computer) more than the recommended limit of 2 h/d, but little is known about
      parents' role in mediating their children's media use. DESIGN: Office-based
      survey. Data were collected on demographics, reported media behaviors, parental
      awareness about media effects, television in the bedroom, and parental concern.
      We developed logistic regression models to examine factors associated with the
      following 3 mediation approaches: restrictive, instructive, and unlimited.
      SETTING: Pediatric Research in Office Settings practices. PARTICIPANTS: Parents
      with children aged 2 to 11 years (n = 1831) presenting for a well-child visit.
      RESULTS: Almost half of parents reported a single mediation approach, including
      restrictive for 23%, instructive for 11%, and unlimited for 7%, with 59%
      reporting the use of multiple strategies. Restrictive (odds ratio [OR], 1.16;
      P<.001) and instructive (OR, 1.06; P = .02) approaches were associated with
      increased awareness about negative media effects, whereas a decreased awareness
      existed for those who used an unlimited approach (OR, 0.87; P<.001). A
      restrictive strategy also occurred with increased parental concern (OR, 1.77;
      P<.001) and 2 adults in the home (OR, 1.64; P<.01). The only strategy associated
      with the child's age was instructive mediation, noted more often with younger
      children (OR, 1.41; P<.001). Allowing unlimited media use occurred when parents
      permitted a television in the child's bedroom (OR, 2.13; P<.001) and were Latino
      (OR, 2.03; P<.01) or African American (OR, 2.20; P<.001). Mother as primary
      decision maker and maternal education were not statistically significant.
      CONCLUSIONS: Pediatric health care providers should identify parental practices
      and reinforce active media mediation strategies.

PMID- 16585486
TI  - Content and ratings of mature-rated video games.
AB  - OBJECTIVES: To quantify the depiction of violence, blood, sexual themes,
      profanity, substances, and gambling in video games rated M (for "mature") and to
      measure agreement between the content observed and the rating information
      provided to consumers on the game box by the Entertainment Software Rating Board.
      DESIGN: We created a database of M-rated video game titles, selected a random
      sample, recorded at least 1 hour of game play, quantitatively assessed the
      content, performed statistical analyses to describe the content, and compared our
      observations with the Entertainment Software Rating Board content descriptors and
      results of our prior studies. SETTING: Harvard University, Boston, Mass.
      PARTICIPANTS: Authors and 1 hired game player. MAIN EXPOSURE: M-rated video
      games. MAIN OUTCOME MEASURES: Percentages of game play depicting violence, blood,
      sexual themes, gambling, alcohol, tobacco, or other drugs; use of profanity in
      dialogue, song lyrics, or gestures. RESULTS: Although the Entertainment Software
      Rating Board content descriptors for violence and blood provide a good indication
      of such content in the game, we identified 45 observations of content that could
      warrant a content descriptor in 29 games (81%) that lacked these content
      descriptors. M-rated video games are significantly more likely to contain blood,
      profanity, and substances; depict more severe injuries to human and nonhuman
      characters; and have a higher rate of human deaths than video games rated T (for
      "teen"). CONCLUSION: Parents and physicians should recognize that popular M-rated
      video games contain a wide range of unlabeled content and may expose children and
      adolescents to messages that may negatively influence their perceptions,
      attitudes, and behaviors.

PMID- 16585487
TI  - Metabolic and physiologic responses to video game play in 7- to 10-year-old boys.
AB  - OBJECTIVE: To examine the metabolic, physiologic, and hemostatic responses to
      action video game play in a group of young boys. DESIGN: Comparison study.
      SETTING: Laboratory of Clinical and Applied Physiology, University of Miami.
      PARTICIPANTS: Twenty-one boys aged 7 to 10 years. MAIN OUTCOME MEASURES: Blood
      pressure monitored before and during game play and blood glucose and lactate
      levels measured before and immediately after game play. Measurements were
      continuously recorded throughout game play. Dependent t tests were used to
      compare measurements recorded at baseline and during or after game play. Effect
      sizes using the Cohen d were examined for comparisons. RESULTS: Significant
      increases from baseline were found for heart rate (18.8%; P<.001), systolic
      (22.3%; P<.001) and diastolic (5.8%; P = .006) blood pressure, ventilation
      (51.9%; P<.001), respiratory rate (54.8%; P<.001), oxygen consumption (49.0%;
      P<.001), and energy expenditure (52.9%; P<.001). Effect sizes for these
      comparisons were medium or large. No significant changes were found from baseline
      to after video game play for lactate (18.2% increase; P = .07) and glucose (0.9%
      decrease; P = .59) levels. CONCLUSIONS: Video game play results in significant
      increases in various metabolic and physiologic variables in young children. Thus,
      it should not be combined with television viewing for the evaluation of sedentary
      activities. The magnitude of change, however, was lower than that observed during
      standard physical exercise and below national health recommendations. As such,
      video game play should not be considered a substitute for regular physical
      activities that significantly stress the metabolic pathways required for the
      promotion of cardiovascular conditioning.

PMID- 16585488
TI  - Television exposure and overweight risk in preschoolers.
AB  - OBJECTIVE: To test the independent effect of television exposure in preschool
      aged children on overweight risk. DESIGN: Cross-sectional and longitudinal
      analysis of the National Institute of Child Health and Human Development Study of
      Early Child Care and Youth Development. SETTING: Ten US sites. PARTICIPANTS: One
      thousand sixteen children selected via conditional random sampling. MAIN
      EXPOSURE: Being awake in the room with the television on for 2 hours or more per
      day, by maternal report at age 36 months. MAIN OUTCOME MEASURES: Child overweight
      (body mass index [calculated as weight in kilograms divided by the square of
      height in meters] > or =95th percentile) calculated from measured anthropometrics
      at ages 36 and 54 months. Covariates tested included child sex and race; maternal
      marital status, education, age, and depressive symptoms; income-needs ratio,
      child behavior problems; Home Observation for Measurement of the Environment
      total score; hours per week in nonparental care; and proportion of television
      exposure that was educational. RESULTS: At age 36 months, 5.8% of children were
      overweight; at age 54 months, 10.0% were overweight. Exposure to 2 or more hours
      of television per day was associated with an increased risk of overweight at both
      age 36 months (odds ratio, 2.92; 95% confidence interval, 1.36-6.24) and age 54
      months (odds ratio, 1.71; 95% confidence interval, 1.03-2.83) in unadjusted
      analyses. Only maternal age altered the concurrent relationship, and the effect
      of television remained significant (odds ratio, 2.61; 95% confidence interval,
      1.21-5.62). Television exposure at age 36 months was no longer a significant
      predictor of overweight at age 54 months when controlling for covariates.
      CONCLUSION: Excessive television exposure is a risk factor for overweight in
      preschoolers independent of a number of potential confounders associated with the
      quality of the home environment.

PMID- 16585489
TI  - Parental weight status as a moderator of the relationship between television
      viewing and childhood overweight.
AB  - OBJECTIVE: To examine whether and to what extent the relationship between
      television viewing and children's weight status differs according to parental
      weight status. DESIGN: Population-level survey including in-home and telephone
      interview components. SETTING: United States. PARTICIPANTS: Representative sample
      of children aged 6 to 19 years in 2002 (n = 1483). MAIN EXPOSURE: Hours of
      television viewing. MAIN OUTCOME MEASURES: Child weight status (normal weight, at
      risk for overweight, overweight) as defined by current Centers for Disease
      Control and Prevention standards. RESULTS: Parental obesity increased the risk of
      child overweight for all of the children except boys aged 6 to 9 years. There
      were significant interactions between television viewing hours and parental
      obesity among boys aged 14 to 19 years and girls aged 10 to 13 years. For these 2
      groups, the odds of overweight status increased with viewing hours for children
      with at least 1 obese parent but not at all for children of normal-weight
      parents. CONCLUSIONS: Results indicate that when parental obesity is taken into
      account, television viewing hours do not significantly relate to increased odds
      of childhood overweight, and parental body mass index may serve to moderate the
      relationship between television viewing and child weight status among adolescents
      (but not among younger children). Further examination of the moderating effect of
      parental body mass index on the relationship between television viewing and child
      weight status is warranted.

PMID- 16585490
TI  - A content analysis of health and physical activity messages marketed to African
      American children during after-school television programming.
AB  - OBJECTIVE: To examine the number of food advertisements African American children
      are exposed to during children's television programming aired on predominantly
      African American and general television stations. DESIGN: A content analysis was
      conducted to identify and analyze the health-related content (HRC) and physical
      activity-related content (PARC) of food advertisements shown during children's
      television programming. SETTING: Three sets of television advertisements from 3
      stations (Black Entertainment Television, The WB [Warner Bros], and Disney
      Channel) served as the sample during a 1-week period in July 2005 (July 11-15),
      from 3 pm to 9 pm. RESULTS: In total, 1098 advertisements were recorded, with 256
      food and beverage commercials used for this study. Results indicate that 36.3% of
      all commercials were based on fast food restaurants, 31.3% were for drinks, 16.8%
      were for candy, 13.7% were for cereals, and 2.0% were for snacks (percentages do
      not total 100 because of rounding). Compared with The WB and Disney Channel,
      Black Entertainment Television had significantly (P=.001) more food and beverage
      advertisements. Few HRC or PARC advertisements were shown. Of 256 food and
      beverage commercials, only 8.2% contained HRC and 9.4% had PARC. Also, the HRC
      and PARC scenes contained messages that were implied vs explicitly talking about
      the health or physical benefits of the product. CONCLUSIONS: African American
      children are overexposed to numerous types of food and beverage advertisements.
      These advertisements do not provide an adequate level of positive HRC and PARC
      messages. Consequently, the messages that are portrayed may undermine efforts to
      teach African American children about the importance of healthy living and
      physical activity.

PMID- 16585492
TI  - Media as a public health issue.

PMID- 16585491
TI  - When children eat what they watch: impact of television viewing on dietary intake
      in youth.
AB  - OBJECTIVES: To test whether increased television viewing is associated with
      increased total energy intake and with increased consumption of foods commonly
      advertised on television, and to test whether increased consumption of these
      foods mediates the relationship between television viewing and total energy
      intake. DESIGN: Prospective observational study with baseline (fall 1995) and
      follow-up (spring 1997) measures of youth diet, physical activity, and television
      viewing. We used food advertising data to identify 6 food groups for study (sweet
      baked snacks, candy, fried potatoes, main courses commonly served as fast food,
      salty snacks, and sugar-sweetened beverages). SETTING AND PARTICIPANTS: Five
      public schools in 4 communities near Boston. The sample included 548 students
      (mean age at baseline, 11.70 years; 48.4% female; and 63.5% white). MAIN OUTCOME
      MEASURES: Change in total energy intake and intake of foods commonly advertised
      on television from baseline to follow-up. RESULTS: After adjusting for baseline
      covariates, each hour increase in television viewing was associated with an
      additional 167 kcal/d (95% confidence interval, 136-198 kcal/d; P<.001) and with
      increases in the consumption of foods commonly advertised on television.
      Including changes in intakes of these foods in regression models provided
      evidence of their mediating role, diminishing or rendering nonsignificant the
      associations between change in television viewing and change in total energy
      intake. CONCLUSIONS: Increases in television viewing are associated with
      increased calorie intake among youth. This association is mediated by increasing
      consumption of calorie-dense low-nutrient foods frequently advertised on
      television.

PMID- 16585493
TI  - Exploring the impact of media on children: the challenges that remain.

PMID- 16585494
TI  - Effect of media on children and adolescents: it's about time.

PMID- 16585495
TI  - Cranberry therapy for children's urinary tract infections.

PMID- 16585496
TI  - Needle aspiration and intramuscular vaccination.

PMID- 16585497
TI  - Dismissing families: a critical issue.

PMID- 16585498
TI  - Dismissing families: a slippery slope.

PMID- 16585499
TI  - Advocacy by any other name would smell as sweet.

PMID- 16585500
TI  - Profile of Robert W. Mahley.

PMID- 16585501
TI  - In a bovine model of onchocerciasis, protective immunity exists naturally, is
      absent in drug-cured hosts, and is induced by vaccination.
AB  - Onchocerciasis (river blindness) is a major parasitic disease of humans in sub
      Saharan Africa caused by the microfilarial stage of the nematode Onchocerca
      volvulus. Using Onchocerca ochengi, a closely related species which infects
      cattle and is transmitted by the same black fly vector (Simulium damnosum sensu
      lato) as O. volvulus, we have conducted longitudinal studies after either natural
      field exposure or experimental infection to determine whether, and under what
      circumstances, protective immunity exists in onchocerciasis. On the basis of the
      adult worm burdens (nodules) observed, we determined that cattle reared in
      endemic areas without detectable parasites (putatively immune) were significantly
      less susceptible to heavy field challenge than age-matched, naive controls (P =
      0.002), whereas patently infected cattle, cured of infection by adulticide
      treatment with melarsomine, were fully susceptible. Cattle immunized with
      irradiated third-stage larvae were significantly protected against experimental
      challenge (100% reduction in median nodule load, P = 0.003), and vaccination also
      conferred resistance to severe and prolonged field challenge (64% reduction in
      median nodule load, P = 0.053; and a significant reduction in microfilarial
      positivity rates and density, P < 0.05). These results constitute evidence of
      protective immunity in a naturally evolved host-Onchocerca sp. relationship and
      provide proof-of-principle for immunoprophylaxis under experimental and field
      conditions.

PMID- 16585502
TI  - Cytoprotective doses of erythropoietin or carbamylated erythropoietin have
      markedly different procoagulant and vasoactive activities.
AB  - Recombinant human erythropoietin (rhEPO) is receiving increasing attention as a
      potential therapy for prevention of injury and restoration of function in
      nonhematopoietic tissues. However, the minimum effective dose required to mimic
      and augment these normal paracrine functions of erythropoietin (EPO) in some
      organs (e.g., the brain) is higher than for treatment of anemia. Notably, a dose
      dependent risk of adverse effects has been associated with rhEPO administration,
      especially in high-risk groups, including polycythemia-hyperviscosity syndrome,
      hypertension, and vascular thrombosis. Of note, several clinical trials employing
      relatively high dosages of rhEPO in oncology patients were recently halted after
      an increase in mortality and morbidity, primarily because of thrombotic events.
      We recently identified a heteromeric EPO receptor complex that mediates tissue
      protection and is distinct from the homodimeric receptor responsible for the
      support of erythropoiesis. Moreover, we developed receptor-selective ligands that
      provide tools to assess which receptor isoform mediates which biological
      consequence of rhEPO therapy. Here, we demonstrate that rhEPO administration in
      the rat increases systemic blood pressure, reduces regional renal blood flow, and
      increases platelet counts and procoagulant activities. In contrast, carbamylated
      rhEPO, a heteromeric receptor-specific ligand that is fully tissue protective,
      increases renal blood flow, promotes sodium excretion, reduces injury-induced
      elevation in procoagulant activity, and does not effect platelet production.
      These preclinical findings suggest that nonerythropoietic tissue-protective
      ligands, which appear to elicit fewer adverse effects, may be especially useful
      in clinical settings for tissue protection.

PMID- 16585503
TI  - Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of
      IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis.
AB  - Administration of daclizumab, a humanized mAb directed against the IL-2Ralpha
      chain, strongly reduces brain inflammation in multiple sclerosis patients. Here
      we show that daclizumab treatment leads to only a mild functional blockade of
      CD4(+) T cells, the major candidate in multiple sclerosis pathogenesis. Instead,
      daclizumab therapy was associated with a gradual decline in circulating CD4(+)
      and CD8(+) T cells and significant expansion of CD56(bright) natural killer (NK)
      cells in vivo, and this effect correlated highly with the treatment response. In
      vitro studies showed that NK cells inhibited T cell survival in activated
      peripheral blood mononuclear cell cultures by a contact-dependent mechanism.
      Positive correlations between expansion of CD56(bright) NK cells and contraction
      of CD4(+) and CD8(+) T cell numbers in individual patients in vivo provides
      supporting evidence for NK cell-mediated negative immunoregulation of activated T
      cells during daclizumab therapy. Our data support the existence of an
      immunoregulatory pathway wherein activated CD56(bright) NK cells inhibit T cell
      survival. This immunoregulation has potential importance for the treatment of
      autoimmune diseases and transplant rejection and toward modification of tumor
      immunity.

PMID- 16585504
TI  - Determinants of specific RNA interference-mediated silencing of human beta-globin
      alleles differing by a single nucleotide polymorphism.
AB  - A single nucleotide polymorphism (SNP) in the sickle beta-globin gene (beta(S))
      leads to sickle cell anemia. Sickling increases sharply with deoxy sickle Hb
      concentration and decreases with increasing fetal gamma-globin concentration.
      Measures that decrease sickle Hb concentration should have an antisickling
      effect. RNA interference (RNAi) uses small interfering (si)RNAs for sequence
      specific gene silencing. A beta(S) siRNA with position 10 of the guide strand
      designed to align with the targeted beta(S) SNP specifically silences beta(S)
      gene expression without affecting the expression of the gamma-globin or normal
      beta-globin (beta(A)) genes. Silencing is increased by altering the 5' end of the
      siRNA antisense (guide) strand to enhance its binding to the RNA-induced
      silencing complex (RISC). Specific beta(S) silencing was demonstrated by using a
      luciferase reporter and full-length beta(S) cDNA transfected into HeLa cells and
      mouse erythroleukemia cells, where it was expressed in the context of the
      endogenous beta-globin gene promoter and the locus control region enhancers. When
      this strategy was used to target beta(E), silencing was not limited to the mutant
      gene but also targeted the normal beta(A) gene. siRNAs, mismatched with their
      target at position 10, guided mRNA cleavage in all cases except when two bulky
      purines were aligned. The specific silencing of the beta(S)-globin gene, as
      compared with beta(E), as well as studies of silencing SNP mutants in other
      diseases, indicates that siRNAs developed to target a disease-causing SNP will be
      specific if the mutant residue is a pyrimidine and the normal residue is a
      purine.

PMID- 16585506
TI  - Mitigation strategies for pandemic influenza in the United States.
AB  - Recent human deaths due to infection by highly pathogenic (H5N1) avian influenza
      A virus have raised the specter of a devastating pandemic like that of 1917-1918,
      should this avian virus evolve to become readily transmissible among humans. We
      introduce and use a large-scale stochastic simulation model to investigate the
      spread of a pandemic strain of influenza virus through the U.S. population of 281
      million individuals for R(0) (the basic reproductive number) from 1.6 to 2.4. We
      model the impact that a variety of levels and combinations of influenza antiviral
      agents, vaccines, and modified social mobility (including school closure and
      travel restrictions) have on the timing and magnitude of this spread. Our
      simulations demonstrate that, in a highly mobile population, restricting travel
      after an outbreak is detected is likely to delay slightly the time course of the
      outbreak without impacting the eventual number ill. For R(0) < 1.9, our model
      suggests that the rapid production and distribution of vaccines, even if poorly
      matched to circulating strains, could significantly slow disease spread and limit
      the number ill to <10% of the population, particularly if children are
      preferentially vaccinated. Alternatively, the aggressive deployment of several
      million courses of influenza antiviral agents in a targeted prophylaxis strategy
      may contain a nascent outbreak with low R(0), provided adequate contact tracing
      and distribution capacities exist. For higher R(0), we predict that multiple
      strategies in combination (involving both social and medical interventions) will
      be required to achieve similar limits on illness rates.

PMID- 16585505
TI  - Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic
      adenocarcinoma in the mouse.
AB  - Activating KRAS mutations and p16(Ink4a) inactivation are near universal events
      in human pancreatic ductal adenocarcinoma (PDAC). In mouse models, Kras(G12D)
      initiates formation of premalignant pancreatic ductal lesions, and loss of either
      Ink4a/Arf (p16(Ink4a)/p19(Arf)) or p53 enables their malignant progression. As
      recent mouse modeling studies have suggested a less prominent role for p16(Ink4a)
      in constraining malignant progression, we sought to assess the pathological and
      genomic impact of inactivation of p16(Ink4a), p19(Arf), and/or p53 in the
      Kras(G12D) model. Rapidly progressive PDAC was observed in the setting of
      homozygous deletion of either p53 or p16(Ink4a), the latter with intact germ-line
      p53 and p19(Arf) sequences. Additionally, Kras(G12D) in the context of
      heterozygosity either for p53 plus p16(Ink4a) or for p16(Ink4a)/p19(Arf) produced
      PDAC with longer latency and greater propensity for distant metastases relative
      to mice with homozygous deletion of p53 or p16(Ink4a)/p19(Arf). Tumors from the
      double-heterozygous cohorts showed frequent p16(Ink4a) inactivation and loss of
      either p53 or p19(Arf). Different genotypes were associated with specific
      histopathologic characteristics, most notably a trend toward less differentiated
      features in the homozygous p16(Ink4a)/p19(Arf) mutant model. High-resolution
      genomic analysis revealed that the tumor suppressor genotype influenced the
      specific genomic patterns of these tumors and showed overlap in regional
      chromosomal alterations between murine and human PDAC. Collectively, our results
      establish that disruptions of p16(Ink4a) and the p19(ARF)-p53 circuit play
      critical and cooperative roles in PDAC progression, with specific tumor
      suppressor genotypes provocatively influencing the tumor biological phenotypes
      and genomic profiles of the resultant tumors.

PMID- 16585507
TI  - Water dynamics and salt-activation of enzymes in organic media: mechanistic
      implications revealed by NMR spectroscopy.
AB  - Deuterium spin relaxation was used to examine the motion of enzyme-bound water on
      subtilisin Carlsberg co-lyophilized with inorganic salts for activation in
      different organic solvents. Spectral editing was used to ensure that the
      relaxation times were associated with relatively mobile deuterons, which were
      contributed almost entirely by D(2)O rather than hydrogen-deuteron exchange on
      the protein. The results indicate that the timescale of motion for residual water
      molecules on the biocatalyst, (tau(c))(D(2)O), in hexane decreased from 65 ns
      (salt-free) to 0.58 ns (98% CsF) as (k(cat)/K(M))(app) of the biocatalyst
      preparation increased from 0.092 s(-1) x M(-1) (salt-free) to 1,140 s(-1) x M(-1)
      (98% CsF). A similar effect was apparent in acetone; the timescale decreased from
      24 ns (salt-free) to 2.87 ns (98% KF), with a corresponding increase in
      (k(cat)/K(M))(app) of 0.140 s(-1) x M(-1) (salt-free) to 12.8 s(-1) x M(-1) (98%
      KF). Although a global correlation between water mobility and enzyme activity was
      not evident, linear correlations between ln[(k(cat)/K(M))(app)] and
      (tau(c))(D(2)O) were obtained for salt-activated enzyme preparations in both
      hexane and acetone. Furthermore, a direct correlation was evident between
      (k(cat)/K(M))(app) and the total amount of mobile water per mass of enzyme. These
      results suggest that increases in enzyme-bound water mobility mediated by the
      presence of salt act as a molecular lubricant and enhance enzyme flexibility in a
      manner functionally similar to temperature. Greater flexibility may permit a
      larger degree of local transition-state mobility, reflected by a more positive
      entropy of activation, for the salt-activated enzyme compared with the salt-free
      enzyme. This increased mobility may contribute to the dramatic increases in
      biocatalyst activity.

PMID- 16585508
TI  - Ligand-induced and nonfusogenic dissolution of a viral membrane.
AB  - Hitherto, all enveloped viruses were thought to shed their lipid membrane during
      entry into cells by membrane fusion. The extracellular form of Vaccinia virus has
      two lipid envelopes surrounding the virus core, and consequently a single fusion
      event will not deliver a naked core into the cell. Here we report a previously
      underscribed mechanism in which the outer viral membrane is disrupted by a ligand
      induced nonfusogenic reaction, followed by the fusion of the inner viral membrane
      with the plasma membrane and penetration of the virus core into the cytoplasm.
      The dissolution of the outer envelope depends on interactions with cellular
      polyanionic molecules and requires the virus glycoproteins A34 and B5. This
      discovery represents a remarkable example of how viruses manipulate biological
      membranes, solves the topological problem of how a double-enveloped virus enters
      cells, reveals a new effect of polyanions on viruses, and provides a therapeutic
      approach for treatment of poxvirus infections, such as smallpox.

PMID- 16585509
TI  - The Arabidopsis homolog of trithorax, ATX1, binds phosphatidylinositol 5
      phosphate, and the two regulate a common set of target genes.
AB  - The Arabidopsis homolog of trithorax, ATX1, regulates numerous functions in
      Arabidopsis beyond the homeotic genes. Here, we identified genome-wide targets of
      ATX1 and showed that ATX1 is a receptor for a lipid messenger,
      phosphatidylinositol 5-phosphate, PI5P. PI5P negatively affects ATX1 activity,
      suggesting a regulatory pathway connecting lipid-signaling with nuclear
      functions. We propose a model to illustrate how plants may respond to stimuli
      (external or internal) that elevate cellular PI5P levels by altering expression
      of ATX1-controlled genes.

PMID- 16585511
TI  - The expression level of the voltage-dependent anion channel controls life and
      death of the cell.
AB  - Mitochondria not only generate cellular energy, but also act as the point for
      cellular decisions leading to apoptosis. The voltage-dependent anion channel
      (VDAC), as a major mitochondrial outer-membrane transporter, has an important
      role in energy production by controlling metabolite traffic and is also
      recognized as a key protein in mitochondria-mediated apoptosis. In this study,
      the role of VDAC1 in regulating cell survival and death was investigated by
      silencing endogenous human (h)VDAC1 expression by using a short hairpin RNA
      (shRNA)-expressing vector. The shRNA effectively down-regulated the expression in
      human T-REx-293 cells of hVDAC1 but not murine (m)VDAC1. Cells in which hVDAC1
      expression was decreased by approximately 90% proliferated extremely slowly.
      Normal growth was, however, restored upon expression of mVDAC1 in a tetracycline
      regulated manner. Although low tetracycline concentrations promoted cell growth,
      high concentrations induced mVDAC1 overexpression, leading to cell death. Cells
      with low levels of VDAC1 showed 4-fold-lower ATP-synthesis capacity and contained
      low ATP and ADP levels, with a strong correlation between ATP levels and cell
      growth, suggesting limited metabolite exchange between mitochondria and cytosol.
      The possibility of suppressing endogenous hVDAC1 expression and introducing
      native and mutated mVDAC1 is used to further explore the involvement of VDAC1 in
      apoptosis. Cells suppressed for hVDAC1 but expressing either native mVDAC1 or an
      E72Q mutant underwent apoptosis induced by various stimuli that can be inhibited
      by ruthenium red in the native cells but not in the mutated cells, suggesting
      that VDAC1 regulates apoptosis independent of the apoptosis-inducing pathway.

PMID- 16585510
TI  - Identification of genes subject to positive selection in uropathogenic strains of
      Escherichia coli: a comparative genomics approach.
AB  - Escherichia coli is a model laboratory bacterium, a species that is widely
      distributed in the environment, as well as a mutualist and pathogen in its human
      hosts. As such, E. coli represents an attractive organism to study how
      environment impacts microbial genome structure and function. Uropathogenic E.
      coli (UPEC) must adapt to life in several microbial communities in the human
      body, and has a complex life cycle in the bladder when it causes acute or
      recurrent urinary tract infection (UTI). Several studies designed to identify
      virulence factors have focused on genes that are uniquely represented in UPEC
      strains, whereas the role of genes that are common to all E. coli has received
      much less attention. Here we describe the complete 5,065,741-bp genome sequence
      of a UPEC strain recovered from a patient with an acute bladder infection and
      compare it with six other finished E. coli genome sequences. We searched 3,470
      ortholog sets for genes that are under positive selection only in UPEC strains.
      Our maximum likelihood-based analysis yielded 29 genes involved in various
      aspects of cell surface structure, DNA metabolism, nutrient acquisition, and UTI.
      These results were validated by resequencing a subset of the 29 genes in a panel
      of 50 urinary, periurethral, and rectal E. coli isolates from patients with UTI.
      These studies outline a computational approach that may be broadly applicable for
      studying strain-specific adaptation and pathogenesis in other bacteria.

PMID- 16585512
TI  - Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain
      tumor cell growth and invasion and prolongs survival.
AB  - Malignant gliomas remain incurable brain tumors because of their diffuse-invasive
      growth. So far, the genetic and molecular events underlying gliomagenesis are
      poorly understood. In this study, we have identified the receptor tyrosine kinase
      Axl as a mediator of glioma growth and invasion. We demonstrate that Axl and its
      ligand Gas6 are overexpressed in human glioma cell lines and that Axl is
      activated under baseline conditions. Furthermore, Axl is expressed at high levels
      in human malignant glioma. Inhibition of Axl signaling by overexpression of a
      dominant-negative receptor mutant (AXL-DN) suppressed experimental gliomagenesis
      (growth inhibition >85%, P < 0.05) and resulted in long-term survival of mice
      after intracerebral glioma cell implantation when compared with Axl wild-type
      (AXL-WT) transfected tumor cells (survival times: AXL-WT, 10 days; AXL-DN, >72
      days). A detailed analysis of the distinct hallmarks of glioma pathology, such as
      cell proliferation, migration, and invasion and tumor angiogenesis, revealed that
      inhibition of Axl signaling interfered with cell proliferation (inhibition 30%
      versus AXL-WT), glioma cell migration (inhibition 90% versus mock and AXL-WT, P <
      0.05), and invasion (inhibition 62% and 79% versus mock and AXL-WT, respectively;
      P < 0.05). This study describes the identification, functional manipulation, in
      vitro and in vivo validation, and preclinical therapeutic inhibition of a target
      receptor tyrosine kinase mediating glioma growth and invasion. Our findings
      implicate Axl in gliomagenesis and validate it as a promising target for the
      development of approaches toward a therapy of these highly aggressive but, as
      yet, therapy-refractory, tumors.

PMID- 16585513
TI  - Single-molecule kinetics reveals signatures of half-sites reactivity in
      dihydroorotate dehydrogenase A catalysis.
AB  - Subunit activity and cooperativity of a homodimeric flavoenzyme, dihydroorotate
      dehydrogenase A (DHODA) from Lactococcus lactis, were characterized by employing
      single-molecule spectroscopy to follow the turnover kinetics of individual DHODA
      molecules, eliminating ensemble averaging. Because the enzyme-bound FMN is
      fluorescent in its oxidized state but not when reduced, a single DHODA molecule
      exhibits stepwise fluorescence changes during turnover, providing a signal to
      determine reaction kinetics and study cooperativity. Our results showed
      significant heterogeneity in the catalytic behaviors of individual dimer
      molecules, with only 40% interconverting between the three possible redox states:
      the fully fluorescent (both subunits oxidized), the half-fluorescent (one subunit
      oxidized and the other reduced), and the nonfluorescent (both subunits reduced).
      Forty percent of the single dimer traces showed turnovers between only the fully
      fluorescent and half-fluorescent states. The remaining 20% of the molecules
      interconverted only between the half-fluorescent state and the nonfluorescent
      state. Kinetic analysis revealed very similar reaction rates in both the
      reductive and oxidative half-reactions for different DHODA dimers. Our single
      molecule data provide strong evidence for half-sites reactivity, in which only
      one subunit reacts at a time. The present study presents an effective way to
      explore the subunit catalytic activity and cooperativity of oligomeric enzymes by
      virtue of single-molecule fluorescence.

PMID- 16585514
TI  - Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase.
AB  - In Anopheles gambiae, the vector for the most deadly malaria parasite Plasmodium
      falciparum, xanthurenic acid (XA) plays a key role in parasite gametogenesis and
      fertility. In mosquitoes, XA is produced by transamination of 3-hydroxykynurenine
      (3-HK), a reaction that represents the main route to prevent the accumulation of
      the potentially toxic 3-HK excess. Interfering with XA metabolism in A. gambiae
      therefore appears an attractive avenue for the development of malaria
      transmission-blocking drugs and insecticides. We have determined the crystal
      structure of A. gambiae 3-HK transaminase in its pyridoxal 5'-phosphate form and
      in complex with a newly synthesized competitive enzyme inhibitor. Structural
      inspection of the enzyme active site reveals the key molecular determinants for
      ligand recognition and catalysis. Major contributions toward inhibitor binding
      are provided by a salt bridge between the inhibitor carboxylate and Arg-356 and
      by a remarkable hydrogen bond network involving the anthranilic moiety of the
      inhibitor and backbone atoms of residues Gly-25 and Asn-44. This study may be
      useful for the structure-based design of specific enzyme inhibitors of potential
      interest as antimalarial agents.

PMID- 16585515
TI  - Dimerized Drosophila myosin VIIa: a processive motor.
AB  - The molecular mechanism of processive movement of single myosin molecules from
      classes V and VI along their actin tracks has recently attracted extraordinary
      attention. Another member of the myosin superfamily, myosin VII, plays vital
      roles in the sensory function of Drosophila and mammals. We studied the molecular
      mechanism of Drosophila myosin VIIa, using transient kinetics and single-molecule
      motility assays. Myosin VIIa moves along actin filaments as a processive, double
      headed single molecule when dimerized by the inclusion of a leucine zipper at the
      C terminus of the coiled-coil domain. Its motility is approximately 8-10 times
      slower than that of myosin V, and its step size is 30 nm, which is consistent
      with the presence of five IQ motifs in its neck region. The kinetic basis for the
      processive motility of myosin VIIa is the relative magnitude of the release rate
      constants of phosphate (fast) and ADP (slow) as in myosins V and VI. The ATPase
      pathway is rate-limited by a reversible interconversion between two distinct ADP
      bound actomyosin states, which results in high steady-state occupancy of a
      strongly actin-bound myosin species. The distinctive features of myosin VIIa
      (long run lengths, slow motility) will be very useful in video-based single
      molecule applications. In cells, this kinetic behavior would allow myosin VIIa to
      exert and hold tension on actin filaments and, if dimerized, to function as a
      processive cargo transporter.

PMID- 16585516
TI  - Quorum-sensing regulation governs bacterial adhesion, biofilm development, and
      host colonization in Pantoea stewartii subspecies stewartii.
AB  - The phytopathogenic bacterium Pantoea stewartii subsp. stewartii synthesizes
      stewartan exo/capsular polysaccharide (EPS) in a cell density-dependent manner
      governed by the EsaI/EsaR quorum-sensing (QS) system. This study analyzes biofilm
      development and host colonization of the WT and QS regulatory mutant strains of
      P. stewartii. First, we show that the cell density-dependent synthesis of
      stewartan EPS, governed by the EsaI/EsaR QS system, is required for proper
      bacterial adhesion and development of spatially defined, 3D biofilms. Second, a
      nonvirulent mutant lacking the esaI gene adheres strongly to surfaces and
      develops densely packed, less structurally defined biofilms in vitro. This strain
      appears to be arrested in a low cell density developmental mode. Exposure of this
      strain to exogenous N-acyl-homoserine lactone counteracts this adhesion
      phenotype. Third, QS mutants lacking the EsaR repressor attach poorly to surfaces
      and form amorphous biofilms heavily enmeshed in excess EPS. Fourth, the WT strain
      disseminates efficiently within the xylem, primarily in a basipetal direction. In
      contrast, the two QS mutant strains remain largely localized at the site of
      infection. Fifth, and most significantly, epifluorescence microscopic imaging of
      infected leaf tissue and excised xylem vessels reveals that the bacteria colonize
      the xylem with unexpected specificity, particularly toward the annular rings and
      spiral secondary wall thickenings of protoxylem, as opposed to indiscriminate
      growth to fill the xylem lumen. These observations are significant to bacterial
      plant pathogenesis in general and may reveal targets for disease control.

PMID- 16585517
TI  - A base-excision DNA-repair protein finds intrahelical lesion bases by fast
      sliding in contact with DNA.
AB  - A central mystery in the function of site-specific DNA-binding proteins is the
      detailed mechanism for rapid location and binding of target sites in DNA. Human
      oxoguanine DNA glycosylase 1 (hOgg1), for example, must search out rare 8
      oxoguanine lesions to prevent transversion mutations arising from oxidative
      stress. Here we report high-speed imaging of single hOgg1 enzyme molecules
      diffusing along DNA stretched by shear flow. Salt-concentration-dependent
      measurements reveal that such diffusion occurs as hOgg1 slides in persistent
      contact with DNA. At near-physiologic pH and salt concentration, hOgg1 has a
      subsecond DNA-binding time and slides with a diffusion constant as high as 5 x
      10(6) bp(2)/s. Such a value approaches the theoretical upper limit for one
      dimensional diffusion and indicates an activation barrier for sliding of only 0.5
      kcal/mol (1 kcal = 4.2 kJ). This nearly barrierless Brownian sliding indicates
      that DNA glycosylases locate lesion bases by a massively redundant search in
      which the enzyme selectively binds 8-oxoguanine under kinetic control.

PMID- 16585518
TI  - Self-assembled bifunctional surface mimics an enzymatic and templating protein
      for the synthesis of a metal oxide semiconductor.
AB  - The recent discovery and characterization of silicatein, a mineral-synthesizing
      enzyme that assembles to form the filamentous organic core of the glassy skeletal
      elements (spicules) of a marine sponge, has led to the development of new low
      temperature synthetic routes to metastable semiconducting metal oxides. These
      protein filaments were shown in vitro to catalyze the hydrolysis and structurally
      direct the polycondensation of metal oxides at neutral pH and low temperature.
      Based on the confirmation of the catalytic mechanism and the essential
      participation of specific serine and histidine residues (presenting a
      nucleophilic hydroxyl and a nucleophilicity-enhancing hydrogen-bonding imidazole
      nitrogen) in silicatein's catalytic active site, we therefore sought to develop a
      synthetic mimic that provides both catalysis and the surface determinants
      necessary to template and structurally direct heterogeneous nucleation through
      condensation. Using lithographically patterned poly(dimethylsiloxane) stamps,
      bifunctional self-assembled monolayer surfaces containing the essential catalytic
      and templating elements were fabricated by using alkane thiols microcontact
      printed on gold substrates. The interface between chemically distinct self
      assembled monolayer domains provided the necessary juxtaposition of nucleophilic
      (hydroxyl) and hydrogen-bonding (imidazole) agents to catalyze the hydrolysis of
      a gallium oxide precursor and template the condensed product to form gallium
      oxohydroxide (GaOOH) and the defect spinel, gamma-gallium oxide (gamma
      Ga(2)O(3)). Using this approach, the production of patterned substrates for
      catalytic synthesis and templating of semiconductors for device applications can
      be envisioned.

PMID- 16585519
TI  - Self-organized similarity, the evolutionary emergence of groups of similar
      species.
AB  - Ecologists have long been puzzled by the fact that there are so many similar
      species in nature. Here we show that self-organized clusters of look-a-likes may
      emerge spontaneously from coevolution of competitors. The explanation is that
      there are two alternative ways to survive together: being sufficiently different
      or being sufficiently similar. Using a model based on classical competition
      theory, we demonstrate a tendency for evolutionary emergence of regularly spaced
      lumps of similar species along a niche axis. Indeed, such lumpy patterns are
      commonly observed in size distributions of organisms ranging from algae,
      zooplankton, and beetles to birds and mammals, and could not be well explained by
      earlier theory. Our results suggest that these patterns may represent self
      constructed niches emerging from competitive interactions. A corollary of our
      findings is that, whereas in species-poor communities sympatric speciation and
      invasion of open niches is possible, species-saturated communities may be
      characterized by convergent evolution and invasion by look-a-likes.

PMID- 16585520
TI  - Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and
      functional expression of epithelial sodium channels.
AB  - The members of the cytoplasmic 70-kDa heat shock protein family are involved in
      appropriate folding and trafficking of newly synthesized proteins in the cell.
      Hsc70, which is expressed constitutively, and Hsp70, the expression of which is
      stress- and heat shock-induced, are often considered to have similar cellular
      functions in this regard, but there are suggestions that the intracellular
      functions of these homologous but not identical proteins may differ. We tested
      the hypothesis that Hsc70 and Hsp70 would have differential effects on the
      expression of the epithelial sodium channel (ENaC). In Xenopus oocytes,
      overexpression of human Hsc70 decreased the functional (defined as amiloride
      sensitive whole-oocyte current) and surface expression of murine ENaC (mENaC) in
      a concentration-dependent fashion. In contrast, coinjection of a moderate amount
      of Hsp70 cRNA (10 ng) increased the functional and surface expression of mENaC,
      whereas a higher amount of coinjected Hsp70 cRNA (30 ng) decreased mENaC
      functional and surface expression. The increase in mENaC functional expression
      with coinjection of 10 ng of Hsp70 cRNA was antagonized by the additional
      coinjection of Hsc70 cRNA in a concentration-dependent fashion. These data are
      consistent with Hsc70 and Hsp70 having differential and antagonistic effects with
      regard to the intracellular trafficking of mENaC in oocytes, which may have an
      impact on our understanding and potential treatment of diseases of aberrant ion
      channel trafficking.

PMID- 16585521
TI  - Consequences of the selective blockage of chaperone-mediated autophagy.
AB  - Chaperone-mediated autophagy (CMA) is a selective pathway for the degradation of
      cytosolic proteins in lysosomes. CMA declines with age because of a decrease in
      the levels of lysosome-associated membrane protein (LAMP) type 2A, a lysosomal
      receptor for this pathway. We have selectively blocked the expression of LAMP-2A
      in mouse fibroblasts in culture and analyzed the cellular consequences of reduced
      CMA activity. CMA-defective cells maintain normal rates of long-lived protein
      degradation by up-regulating macroautophagy, the major form of autophagy.
      Constitutive up-regulation of macroautophagy is unable, however, to compensate
      for all CMA functions. Thus, CMA-defective cells are more sensitive to stressors,
      suggesting that, although protein turnover is maintained, the selectivity of CMA
      is necessary as part of the cellular response to stress. Our results also denote
      the existence of cross-talk among different forms of autophagy.

PMID- 16585522
TI  - Adhesion of single bacterial cells in the micronewton range.
AB  - The adhesion of bacteria to surfaces plays critical roles in the environment,
      disease, and industry. In aquatic environments, Caulobacter crescentus is one of
      the first colonizers of submerged surfaces. Using a micromanipulation technique,
      we measured the adhesion force of single C. crescentus cells attached to
      borosilicate substrates through their adhesive holdfast. The detachment forces
      measured for 14 cells ranged over 0.11 to 2.26 microN, averaging 0.59 +/- 0.62
      microN. Based on the calculation of stress distribution with the finite element
      analysis method (dividing an object into small grids and calculating relevant
      parameters for all of the elements), the adhesion strength between the holdfast
      and the substrate is >68 N/mm(2) in the central region of contact. To our
      knowledge, this strength of adhesion is the strongest ever measured for
      biological adhesives.

PMID- 16585523
TI  - Short circuit of water vapor and polluted air to the global stratosphere by
      convective transport over the Tibetan Plateau.
AB  - During boreal summer, much of the water vapor and CO entering the global tropical
      stratosphere is transported over the Asian monsoon/Tibetan Plateau (TP) region.
      Studies have suggested that most of this transport is carried out either by
      tropical convection over the South Asian monsoon region or by extratropical
      convection over southern China. By using measurements from the newly available
      National Aeronautics and Space Administration Aura Microwave Limb Sounder, along
      with observations from the Aqua and Tropical Rainfall-Measuring Mission
      satellites, we establish that the TP provides the main pathway for cross
      tropopause transport in this region. Tropospheric moist convection driven by
      elevated surface heating over the TP is deeper and detrains more water vapor, CO,
      and ice at the tropopause than over the monsoon area. Warmer tropopause
      temperatures and slower-falling, smaller cirrus cloud particles in less saturated
      ambient air at the tropopause also allow more water vapor to travel into the
      lower stratosphere over the TP, effectively short-circuiting the slower ascent of
      water vapor across the cold tropical tropopause over the monsoon area. Air that
      is high in water vapor and CO over the Asian monsoon/TP region enters the lower
      stratosphere primarily over the TP, and it is then transported toward the Asian
      monsoon area and disperses into the large-scale upward motion of the global
      stratospheric circulation. Thus, hydration of the global stratosphere could be
      especially sensitive to changes of convection over the TP.

PMID- 16585524
TI  - Viral and therapeutic control of IFN-beta promoter stimulator 1 during hepatitis
      C virus infection.
AB  - Viral signaling through retinoic acid-inducible gene-I (RIG-I) and its adaptor
      protein, IFN promoter-stimulator 1 (IPS-1), activates IFN regulatory factor-3
      (IRF-3) and the host IFN-alpha/beta response that limits virus infection. The
      hepatitis C virus (HCV) NS3/4A protease cleaves IPS-1 to block RIG-I signaling,
      but how this regulation controls the host response to HCV is not known. Moreover,
      endogenous IPS-1 cleavage has not been demonstrated in the context of HCV
      infection in vitro or in vivo. Here, we show that HCV infection transiently
      induces RIG-I- and IPS-1-dependent IRF-3 activation. This host response limits
      HCV production and constrains cellular permissiveness to infection. However, HCV
      disrupts this response early in infection by NS3/4A cleavage of IPS-1 at C508,
      releasing IPS-1 from the mitochondrial membrane. Cleavage results in subcellular
      redistribution of IPS-1 and loss of interaction with RIG-I, thereby preventing
      downstream activation of IRF-3 and IFN-beta induction. Liver tissues from
      chronically infected patients similarly demonstrate subcellular redistribution of
      IPS-1 in infected hepatocytes and IPS-1 cleavage associated with a lack of ISG15
      expression and conjugation of target proteins in vivo. Importantly, small
      molecule inhibitors of NS3/4A prevent cleavage and restore RIG-I signaling of IFN
      beta induction. Our results suggest a dynamic model in which early activation of
      IRF-3 and induction of antiviral genes are reversed by IPS-1 proteolysis and
      abrogation of RIG-I signaling as NS3/4A accumulates in newly infected cells. HCV
      protease inhibitors effectively prevent IPS-1 proteolysis, suggesting they may be
      capable of restoring this innate host response in clinical practice.

PMID- 16585525
TI  - High expression of a cytokeratin-associated protein in many cancers.
AB  - We have described previously a cDNA library made from membrane-bound polysomal
      mRNA prepared from breast and prostate cancer cell lines. The library is highly
      enriched for cDNAs encoding membrane proteins, secreted proteins, and
      cytokeratins. To characterize this library, 25,277 cDNA clones were sequenced and
      aligned with various databases; 1,439 clones did not align with known genes. From
      this set of clones we identified a previously uncharacterized gene encoding a 334
      aa protein. Although protein structural motif prediction programs indicate that
      the gene encodes a membrane protein comprising a signal sequence, a series of
      leucine-rich repeats, and a single transmembrane domain with a cytoplasmic tail,
      confocal microscopy of MCF7 breast cancer cells demonstrates that the protein is
      not directly associated with the plasma membrane or intracellular membranes but
      instead colocalizes with intermediate filaments and cytokeratins within the cell.
      Immunofluorescence studies also show that protein expression is increased greatly
      in mitotic MCF7 cells, and immunohistochemistry demonstrates its expression in
      human breast cancer cells. Analysis of mRNA levels in 25 different normal tissues
      by RT-PCR shows that this gene is expressed highly in normal prostate and
      salivary gland, very weakly in colon, pancreas, and intestine, and not at all in
      other tissues. RT-PCR studies on human cancer samples show that the RNA is
      expressed highly in many cancer cell lines and cancer specimens, including 26 of
      33 human breast cancers, 3 of 3 prostate cancers, 3 of 3 colon cancers, and 3 of
      3 pancreatic cancers. We name the protein CAPC, cytokeratin-associated protein in
      cancer.

PMID- 16585526
TI  - DNA strand breaks induced by near-zero-electronvolt electron attachment to
      pyrimidine nucleotides.
AB  - To elucidate the mechanism of DNA strand breaks by low-energy electrons (LEE),
      theoretical investigations of the LEE attachment-induced C(5')-O(5') sigma bond
      breaking of pyrimidine nucleotides (5'-dCMPH and 5'-dTMPH) were performed by
      using the B3LYP/DZP++ approach. The results indicate that the pyrimidine
      nucleotides are able to capture electrons characterized by near-0-eV energy to
      form electronically stable radical anions in both the gas phase and aqueous
      solution. The mechanism of the LEE-induced single-strand bond breaking in DNA
      might involve the attachment of an electron to the bases of DNA and the formation
      of base-centered radical anions in the first step. Subsequently, these radical
      anions undergo either C-O or glycosidic bond breaking, yielding neutral ribose
      radical fragments and the corresponding phosphoric anions or base anions. The C-O
      bond cleavage is expected to dominate because of its low activation energy. In
      aqueous solutions, the significant increases in the electron affinities of
      pyrimidine nucleotides ensure the formation of electronically more stable radical
      anions of the nucleotides. The low activation energy barriers for the C(5')-O(5')
      bond breaking predicted in this work are relevant when the counterions are close
      enough to the phosphate moiety of DNA.

PMID- 16585527
TI  - Natural selection and molecular evolution in primate PAX9 gene, a major
      determinant of tooth development.
AB  - Large differences in relation to dental size, number, and morphology among and
      within modern human populations and between modern humans and other primate
      species have been observed. Molecular studies have demonstrated that tooth
      development is under strict genetic control, but, the genetic basis of primate
      tooth variation remains unknown. The PAX9 gene, which codes for a paired domain
      containing transcription factor that plays an essential role in the development
      of mammal dentition, has been associated with selective tooth agenesis in humans
      and mice, which mainly involves the posterior teeth. To determine whether this
      gene is polymorphic in humans, we sequenced approximately 2.1 kb of the entire
      four-exon region (exons 1, 2, 3 and 4; 1,026 bp) and exon-intron (1.1 kb)
      boundaries of 86 individuals sampled from Asian, European, and Native American
      populations. We provided evidence that human PAX9 polymorphisms are limited to
      exon 3 only and furnished details about the distribution of a mutation there in
      350 Polish subjects. To investigate the pattern of selective pressure on exon 3,
      we sequenced ortholog regions of this exon in four species of New World monkeys
      and one gorilla. In addition, orthologous sequences of PAX9 available in public
      databases were also analyzed. Although several differences were identified
      between humans and other species, our findings support the view that strong
      purifying selection is acting on PAX9. New World and Old World primate lineages
      may, however, have different degrees of restriction for changes in this DNA
      region.

PMID- 16585528
TI  - Immunological synapse arrays: patterned protein surfaces that modulate
      immunological synapse structure formation in T cells.
AB  - T cells are activated by recognition of foreign peptides displayed on the surface
      of antigen presenting cells (APCs), an event that triggers assembly of a complex
      microscale structure at the T cell-APC interface known as the immunological
      synapse (IS). It remains unresolved whether the unique physical structure of the
      synapse itself impacts the functional response of T cells, independent of the
      quantity and quality of ligands encountered by the T cell. As a first step toward
      addressing this question, we created multicomponent protein surfaces presenting
      lithographically defined patterns of tethered T cell receptor (TCR) ligands (anti
      CD3 "activation sites") surrounded by a field of tethered intercellular adhesion
      molecule-1 (ICAM-1), as a model substrate on which T cells could be seeded to
      mimic T cell-APC interactions. CD4(+) T cells seeded on these surfaces polarized
      and migrated; on contact with activation sites, T cells assembled an IS with a
      structure modulated by the physical pattern of ligand encountered. On surfaces
      patterned with focal spots of TCR ligand, T cells stably interacted with
      activation sites, proliferated, and secreted cytokines. In contrast, T cells
      interacting with activation sites patterned to preclude centralized clustering of
      TCR ligand failed to form stable contacts with activation sites, exhibited
      aberrant PKC- clustering in a fraction of cells, and had significantly reduced
      production of IFN-gamma. These results suggest that focal clustering of TCR
      ligand characteristic of the "mature" IS may be required under some conditions
      for full T cell activation.

PMID- 16585529
TI  - Experimental evidence for interspecific directional selection on moth pheromone
      communication.
AB  - The chemical composition of the sexual communication signals of female moths is
      thought to be under strong stabilizing selection, because females that produce
      atypical pheromone blends suffer lower success in finding mates. This
      intraspecific selection pressure cannot explain the high diversity of moth
      pheromone blends found in nature. We conducted experiments to determine whether
      communication interference from males of closely related species could exert
      strong enough directional selection to cause evolution of these signals.
      Attraction and mating success of Heliothis subflexa (Hs) females with a normal
      quantitative trait locus for production of acetate pheromone components (norm
      OAc) were compared with Hs females with an introgressed quantitative trait locus
      from Heliothis virescens (Hv) that dramatically decreased the amount of acetate
      esters in their pheromone glands (low-OAc). In field experiments with natural Hv
      and Hs populations, 10 times more Hv males were captured in traps baited with
      live low-OAc Hs females than in traps with norm-OAc Hs females. This pattern was
      confirmed in mate-choice assays in cages. Hybrids resulting from Hv-Hs matings
      have effectively zero fitness in the field. Combining our results with the
      extensive data set gathered in the past 40 years on the reproductive biology of
      Hv, we can quantitatively estimate that the directional selection exerted by Hv
      males on Hs females to produce relatively high amounts (>5%) of acetates can
      range from 0.135 to 0.231. Such intense interspecific selection may counteract
      intraspecific stabilizing selection that impedes evolutionary changes in
      pheromone blends and could lead to diversification of sexual signals.

PMID- 16585530
TI  - Overlapping hand-over-hand mechanism of single molecular motility of cytoplasmic
      dynein.
AB  - Structural differences between dynein and kinesin suggest a unique molecular
      mechanism of dynein motility. Measuring the mechanical properties of a single
      molecule of dynein is crucial for revealing the mechanisms underlying its
      movement. We measured the step size and force produced by single molecules of
      active cytoplasmic dynein by using an optical trap and fluorescence imaging with
      a high temporal resolution. The velocity of dynein movement, 800 nm/s, is
      consistent with that reported in cells. The maximum force of 7-8 pN was
      independent of the ATP concentration and similar to that of kinesin. Dynein
      exhibited forward and occasional backwards steps of approximately 8 nm,
      independent of load. It is suggested that the large dynein heads take 16-nm steps
      by using an overlapping hand-over-hand mechanism.

PMID- 16585531
TI  - Human vitamin B12 absorption measurement by accelerator mass spectrometry using
      specifically labeled (14)C-cobalamin.
AB  - There is a need for an improved test of human ability to assimilate dietary
      vitamin B(12). Assaying and understanding absorption and uptake of B(12) is
      important because defects can lead to hematological and neurological
      complications. Accelerator mass spectrometry is uniquely suited for assessing
      absorption and kinetics of carbon-14 ((14)C)-labeled substances after oral
      ingestion because it is more sensitive than decay counting and can measure levels
      of (14)C in microliter volumes of biological samples with negligible exposure of
      subjects to radioactivity. The test we describe employs amounts of B(12) in the
      range of normal dietary intake. The B(12) used was quantitatively labeled with
      (14)C at one particular atom of the dimethylbenzimidazole (DMB) moiety by
      exploiting idiosyncrasies of Salmonella metabolism. To grow aerobically on
      ethanolamine, Salmonella enterica must be provided with either preformed B(12) or
      two of its precursors, cobinamide and DMB. When provided with (14)C-DMB
      specifically labeled in the C2 position, cells produced (14)C-B(12) of high
      specific activity (2.1 GBq/mmol, 58 mCi/mmol) (1 Ci = 37 GBq) and no detectable
      dilution of label from endogenous DMB synthesis. In a human kinetic study, a
      physiological dose (1.5 microg, 2.2 kBq/59 nCi) of purified (14)C-B(12) was
      administered and showed plasma appearance and clearance curves consistent with
      the predicted behavior of the pure vitamin. This method opens new avenues for
      study of B(12) assimilation.

PMID- 16585533
TI  - Thousands of samples are needed to generate a robust gene list for predicting
      outcome in cancer.
AB  - Predicting at the time of discovery the prognosis and metastatic potential of
      cancer is a major challenge in current clinical research. Numerous recent studies
      searched for gene expression signatures that outperform traditionally used
      clinical parameters in outcome prediction. Finding such a signature will free
      many patients of the suffering and toxicity associated with adjuvant chemotherapy
      given to them under current protocols, even though they do not need such
      treatment. A reliable set of predictive genes also will contribute to a better
      understanding of the biological mechanism of metastasis. Several groups have
      published lists of predictive genes and reported good predictive performance
      based on them. However, the gene lists obtained for the same clinical types of
      patients by different groups differed widely and had only very few genes in
      common. This lack of agreement raised doubts about the reliability and robustness
      of the reported predictive gene lists, and the main source of the problem was
      shown to be the small number of samples that were used to generate the gene
      lists. Here, we introduce a previously undescribed mathematical method, probably
      approximately correct (PAC) sorting, for evaluating the robustness of such lists.
      We calculate for several published data sets the number of samples that are
      needed to achieve any desired level of reproducibility. For example, to achieve a
      typical overlap of 50% between two predictive lists of genes, breast cancer
      studies would need the expression profiles of several thousand early discovery
      patients.

PMID- 16585532
TI  - B cell clones that sustain long-term plasmablast growth in T-independent
      extrafollicular antibody responses.
AB  - Some antigens induce Ab responses without T lymphocyte help. Among these, many
      polysaccharide-based antigens cause marginal zone B cells to proliferate and
      differentiate into plasma cells. B1 cells also respond to some of these antigens.
      In this article, we report that antigen-specific B1b cells, in response to the T
      independent antigen (4-hydroxy-3-nitrophenyl)-acetyl (NP)-Ficoll, develop into
      clones that sustain Ab production for months with continued production of plasma
      cells and the accumulation of antigen-specific B cells in follicles. The
      persistence of this T-independent plasmablast response contrasts with the short
      term plasmablast growth associated with T-dependent extrafollicular responses.
      The nature of the cells responding to NP-Ficoll was probed by using chimeras that
      have B1 cells but lack primary B lymphopoietic capacity and have very few B2
      cells or T cells. The chimeras were constructed by transferring 10(5) IgM(+) IgD(
      ) peritoneal exudate cells into mice unable to produce their own T and B cells
      because of deficiency in recombinase-activating gene 1 (RAG-1). The chimeras
      mounted sustained IgM and IgG3 anti-NP Ab responses to NP-Ficoll. This finding
      was associated with continued NP-specific extrafollicular plasmablast growth and
      the accumulation of NP-specific B cells in follicles. B cells were not found in
      the marginal zones of chimeras, and they also lacked recirculating IgD(+) cells
      and CD3(+) cells. The absence of B2 and T cells confirms that hemopoietic cell
      chimerism leading to primary lymphopoiesis had not been established.

PMID- 16585534
TI  - Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid
      biosynthesis, and its knockout mice are prone to scurvy.
AB  - We originally identified senescence marker protein 30 (SMP30) as a distinctive
      protein whose expression decreases in an androgen-independent manner with aging.
      Here, we report its sequence homology found in two kinds of bacterial
      gluconolactonases (GNLs) by using the blast search. Then, through a biochemical
      study, we identify SMP30 as the lactone-hydrolyzing enzyme GNL of animal species.
      SMP30 purified from the rat liver had lactonase activity toward various
      aldonolactones, such as d- and l-glucono-delta-lactone, d- and l-gulono-gamma
      lactone, and d- and l-galactono-gamma-lactone, with a requirement for Zn(2+) or
      Mn(2+) as a cofactor. Furthermore, in SMP30 knockout mice, no GNL activity was
      detectable in the liver. Thus, we conclude that SMP30 is a unique GNL in the
      liver. The lactonase reaction with l-gulono-gamma-lactone is the penultimate step
      in l-ascorbic acid (AA) biosynthesis, and the essential role of SMP30 in this
      synthetic process was verified here by a nutritional study using SMP30 knockout
      mice. These knockout mice (n = 6), fed a vitamin C-deficient diet, did not
      thrive; i.e., they displayed symptoms of scurvy such as bone fracture and
      rachitic rosary and then died by 135 days after the start of receiving the
      deficient diet. The AA levels in their livers and kidneys at the time of death
      were <1.6% of those in WT control mice. In addition, by using the SMP30 knockout
      mouse, we demonstrate that the alternative pathway of AA synthesis involving d
      glucurono-gamma-lactone operates in vivo, although its flux is fairly small.

PMID- 16585536
TI  - Comment on "Tumor progression can occur despite the induction of very high levels
      of self/tumor antigen-specific CD8+ T cells in patients with melanoma".

PMID- 16585537
TI  - Comment on "Cutting edge: Extracellular high mobility group box-1 protein is a
      proangiogenic cytokine".

PMID- 16585539
TI  - Memory B cell survival and function in the absence of secreted antibody and
      immune complexes on follicular dendritic cells.
AB  - Ag, in the form of immune complexes retained on follicular dendritic cells, has
      been implicated in the development and maintenance of B cell memory. We addressed
      this question using a H chain transgenic (Tg) mouse model that lacks secreted Ig
      (mIg), and thus does not deposit Ag-containing immune complexes. We compared the
      ability of the mIg strain and a control Tg strain, which secretes IgM, to develop
      and maintain long-lived memory cells. After immunization, there was an increase
      of Ag-specific B cells in both strains that was maintained for at least 20 wk. We
      labeled the long-lived Ag-specific cells with BrdU and found that this population
      was similarly maintained. In addition, both Tgs were able to maintain a
      functional memory response as measured by secondary germinal center reactions.
      Our studies indicate that localization of Ag on follicular dendritic cells is not
      necessary for development and maintenance of B cell memory.

PMID- 16585540
TI  - Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded
      RNA.
AB  - Upon viral infection, host cells trigger antiviral immune responses by inducing
      type I IFN and inflammatory cytokines. dsRNA generated during viral replication
      is recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene I and
      melanoma differentiation-associated gene 5, which interact with an adaptor, IFN
      beta promoter stimulator-1, to activate the transcription factors NF-kappaB and
      IFN regulatory factor 3. In this article we demonstrate that caspase-8 and
      caspase-10 are involved in these pathways. Both caspases were cleaved during
      dsRNA stimulation, and overexpression of a cleaved form of these caspases
      activated NF-kappaB. Knockdown of caspase-10 or caspase-8 in a human cell line
      resulted in the reduction of inflammatory cytokine production. Cells derived from
      caspase-8-deficient mice also showed reduced expression of inflammatory cytokines
      as well as NF-kappaB activation. Furthermore, the Fas-associated death domain
      protein interacted with these two caspases and IFN-beta promoter stimulator 1.
      These results indicate that caspase-8 and caspase-10 are essential components
      that mediate NF-kappaB-dependent inflammatory responses in antiviral signaling.

PMID- 16585541
TI  - CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN
      receptor for clonal expansion.
AB  - The role of type I IFN signaling in CD8 T cells was analyzed in an adoptive
      transfer model using P14 TCR transgenic CD8 T cells specific for lymphocytic
      choriomeningitis virus (LCMV) but deficient in type I IFNR. In the present study,
      we demonstrate severe impairment in the capacity of P14 T cells lacking type I
      IFNR to expand in normal type I IFNR wild-type C57BL/6 hosts after LCMV
      infection. In contrast, following infection of recipient mice with recombinant
      vaccinia virus expressing LCMV glycoprotein, P14 T cell expansion was
      considerably less dependent on type I IFNR expression. Lack of type I IFNR
      expression by P14 T cells did not affect cell division after LCMV infection but
      interfered with clonal expansion. Thus, direct type I IFN signaling is essential
      for CD8 T cell survival in certain viral infections.

PMID- 16585543
TI  - Limited infiltration of exogenous dendritic cells and naive T cells restricts
      immune responses in peripheral lymph nodes.
AB  - Primary CD8 T cell responses in lymph nodes (LN) and protective immunological
      tumor control are quantitatively limited following immunization with exogenous
      peptide-pulsed dendritic cells (DC). This arises from two constraints. First, LN
      are saturated by relatively small quantities of exogenous DC. Second, circulation
      of new naive T cells into DC-infiltrated LN during the functional lifespan of the
      DC is negligible. Limits on DC and T cellularity in, and flux through, LN
      constrain the magnitude of both primary and subsequent recall responses. Enhanced
      immune responses and tumor control can be achieved using maneuvers to augment LN
      retention of DC or availability of naive T cells to Ag-presenting DC. These data
      offer an increased understanding of LN function in general and provide a
      practical basis for improvements in tumor immunotherapy.

PMID- 16585542
TI  - Insufficient perforin expression in CD8+ T cells in response to hemagglutinin
      from avian influenza (H5N1) virus.
AB  - Hypercytokinemia has been considered to be responsible for hemophagocytosis and
      multiorgan failure in severe human cases of H5N1 viral infection. In this study,
      we show a recombinant hemagglutinin (H5) from a H5N1 virus may suppress the
      perforin expression and reduce cytotoxicity of human CD8+ T cells to kill H5
      bearing cells. The persistence of H5-presenting cells provides sustained
      stimulation and leads to a marked lymphoproliferation and IFN-gamma
      hyperproduction. We propose the IFN-gamma hyperproduction may explain macrophage
      overactivation and subsequent hypercytokinemia and hemophagocytosis in severe
      human cases of avian influenza.

PMID- 16585544
TI  - Bruton's tyrosine kinase and SLP-65 regulate pre-B cell differentiation and the
      induction of Ig light chain gene rearrangement.
AB  - Bruton's tyrosine kinase (Btk) and the adapter protein SLP-65 (Src homology 2
      domain-containing leukocyte-specific phosphoprotein of 65 kDa) transmit precursor
      BCR (pre-BCR) signals that are essential for efficient developmental progression
      of large cycling into small resting pre-B cells. We show that Btk- and SLP-65
      deficient pre-B cells have a specific defect in Ig lambda L chain germline
      transcription. In Btk/SLP-65 double-deficient pre-B cells, both kappa and lambda
      germline transcripts are severely reduced. Although these observations point to
      an important role for Btk and SLP-65 in the initiation of L chain gene
      rearrangement, the possibility remained that these signaling molecules are only
      required for termination of pre-B cell proliferation or for pre-B cell survival,
      whereby differentiation and L chain rearrangement is subsequently initiated in a
      Btk/SLP-65-independent fashion. Because transgenic expression of the
      antiapoptotic protein Bcl-2 did not rescue the developmental arrest of Btk/SLP-65
      double-deficient pre-B cells, we conclude that defective L chain opening in
      Btk/SLP-65-deficient small resting pre-B cells is not due to their reduced
      survival. Next, we analyzed transgenic mice expressing the constitutively active
      Btk mutant E41K. The expression of E41K-Btk in Ig H chain-negative pro-B cells
      induced 1) surface marker changes that signify cellular differentiation,
      including down-regulation of surrogate L chain and up-regulation of CD2, CD25,
      and MHC class II; and 2) premature rearrangement and expression of kappa and
      lambda light chains. These findings demonstrate that Btk and SLP-65 transmit
      signals that induce cellular maturation and Ig L chain rearrangement
      independently of their role in termination of pre-B cell expansion.

PMID- 16585545
TI  - Antigen challenge inhibits thymic emigration.
AB  - T cell development in the thymus involves a series of TCR-mediated control points
      including TCR-beta selection and positive and negative selection. Approximately
      half of the thymic sojourn is spent in the medulla, where thymocytes undergo
      final maturation before emigrating to the periphery. Although it is acknowledged
      that thymic emigration is an active process, relatively little is known about how
      this is regulated, why it takes so long, and whether TCR-mediated signaling can
      influence this step. Using wild-type and TCR transgenic mice, we found that Ag
      injected i.v. or intrathymically led to a striking reduction in the number of
      recent thymic emigrants (RTE) in the periphery. This was caused by inhibition of
      T cell export rather than peripheral deletion, because a cohort of RTE that was
      already released before in vivo Ag challenge was not depleted, and similar
      results were observed in Bim-deficient mice, which have impaired T cell deletion.
      Within the thymus, the loss of RTE was associated with retention of medullary
      thymocytes rather than increased negative selection. In addition to Ag-specific
      inhibition of export, some TCR-independent suppression of emigration was also
      observed that appeared to be partly the result of the inflammatory cytokine TNF.
      Thus, in addition to its accepted role in intrathymic selection events, TCR
      signaling can also play an important role in the regulation of thymic emigration.

PMID- 16585546
TI  - DNA methylation by DNA methyltransferase 1 is critical for effector CD8 T cell
      expansion.
AB  - Transcriptional silencing mediated by DNA methylation is a critical component of
      epigenetic regulation during early embryonic development in animals. However, the
      requirement for DNA methylation during activation and differentiation of mature
      CD8+ T cells into effector and memory cells is not clear. Using cre-mediated
      deletion of DNA methyltransferase 1 (Dnmt1) at the time of CD8+ T cell
      activation, we investigated the obligation for maintaining patterns of DNA
      methylation during the generation of Ag-specific effector and memory CD8+ T cells
      in response to acute viral infection of mice with lymphocytic choriomeningitis
      virus. Dnmt1-/- CD8+ T cells failed to undergo the massive CD8+ T cell expansion
      characteristic of lymphocytic choriomeningitis virus infection, leading to >80%
      reductions in Ag-specific effector CD8+ T cells at the height of the response.
      Despite this, Dnmt1-/- CD8+ T cells efficiently controlled the viral infection.
      Interestingly, the number of Ag-specific Dnmt1-/- memory CD8+ T cells was
      moderately reduced compared with the reductions seen at day 8 postinfection. Our
      data suggest that ablation of Dnmt1 and subsequent DNA methylation affect the
      finite proliferative potential of Ag-specific CD8+ T cells with moderate effects
      on their differentiation to effector and memory CD8+ T cells.

PMID- 16585547
TI  - Immune complex-loaded dendritic cells are superior to soluble immune complexes as
      antitumor vaccine.
AB  - Dendritic cells (DCs) play an important role in the induction of T cell
      responses. Fc gammaRs, expressed on DCs, facilitate the uptake of complexed Ag,
      resulting in efficient MHC class I and MHC class II Ag presentation and DC
      maturation. In the present study, we show that prophylactic immunization with DCs
      loaded with Ag-IgG immune complexes (ICs) leads to efficient induction of tumor
      protection in mice. Therapeutic vaccinations strongly delay tumor growth or even
      prevent tumors from growing out. By depleting CD4+ and CD8+ cell populations
      before tumor challenge, we identify CD8+ cells as the main effector cells
      involved in tumor eradication. Importantly, we show that DCs that are preloaded
      in vitro with ICs are at least 1000-fold more potent than ICs injected directly
      into mice or DCs loaded with the same amount of noncomplexed protein. The
      contribution of individual Fc gammaRs to Ag presentation, T cell response
      induction, and induction of tumor protection was assessed. We show that Fc
      gammaRI and Fc gammaRIII are capable of enhancing MHC class I-restricted Ag
      presentation to CD8+ T cells in vitro and that these activating Fc gammaRs on DCs
      are required for efficient priming of Ag-specific CD8+ cells in vivo and
      induction of tumor protection. These findings show that targeting ICs via the
      activating Fc gammaRs to DCs in vitro is superior to direct IC vaccination to
      induce protective tumor immunity in vivo.

PMID- 16585548
TI  - Oral nickel tolerance: Fas ligand-expressing invariant NK T cells promote
      tolerance induction by eliciting apoptotic death of antigen-carrying, effete B
      cells.
AB  - Whereas oral nickel administration to C57BL/6 mice (Ni(high) mice) renders the
      animals tolerant to immunization with NiCl2 combined with H2O2 as adjuvant, as
      determined by ear-swelling assay, it fails to tolerize Jalpha18-/- mice, which
      lack invariant NKT (iNKT) cells. Our previous work also showed that Ni(high)
      splenic B cells can adoptively transfer the nickel tolerance to untreated
      (Ni(low)) recipients, but not to Jalpha18-/- recipients. In this study, we report
      that oral nickel administration increased the nickel content of splenic Ni(high)
      B cells and up-regulated their Fas expression while down-regulating expression of
      bcl-2 and Bcl-xL, thus giving rise to an Ag-carrying, apoptosis-prone B cell
      phenotype. Although oral nickel up-regulated Fas expression on B cells of both
      wild-type Ni(high) and Jalpha18-/- Ni(high) mice, only the former showed a
      reduced number of total B cells in spleen when compared with untreated, syngeneic
      mice, indicating that iNKT cells are involved in B cell homeostasis by eliciting
      apoptosis of effete B cells. Upon transfer of Ni(high) B cells, an infectious
      spread of nickel tolerance ensues, provided the recipients are immunized with
      NiCl2/H2O2. As a consequence of immunization, Fas ligand-positive (FasL+) iNKT
      cells appeared in the spleen and apparently elicited apoptosis of Ni(high) B
      cells. The apoptotic Ni(high) B cells were taken up by splenic dendritic cells,
      which thereby became tolerogenic for nickel-reactive Ni(low) T cells. In
      conclusion, FasL+ iNKT cells may act as ready-to-kill sentinels of innate
      immunity, but at the same time assist in tolerance induction by eliciting
      Fas/FasL-mediated apoptosis of effete, Ag-containing B cells.

PMID- 16585550
TI  - Insufficient APC capacities of dendritic cells in gene gun-mediated DNA
      vaccination.
AB  - Gene gun-mediated DNA immunization is a powerful mode of vaccination against
      infectious diseases and tumors. Many studies have identified dendritic cells (DC)
      as the central players in inducing immunity upon biolistic DNA vaccination;
      however, none of these studies directly quantify DC-mediated responses in
      comparison with immunity triggered by all Ag- and MHC-expressing cells. In this
      study we use two different approaches to decipher the relative role of DC vs
      other cell types in gene gun-induced immunity. First, we directly compared the
      immunization efficacy of different DNA constructs, which allow Ag expression
      ubiquitously (CMV promoter) or specifically in DC (CD11c promoter) and would
      encode either for soluble or membrane bound forms of Ag. Second, we immunized
      transgenic mice in which only DC can present MHC-restricted Ag, and directly
      compared the magnitudes of CTL activation with those obtained in wild-type mice.
      Surprisingly, our combined data suggest that, although DC-specific Ag expression
      is sufficient to induce humoral responses, DC alone cannot trigger optimal CD4
      and CD8 T cell responses upon gene gun vaccination. Therefore, we conclude that
      DC alone are insufficient to mediate optimal induction of T cell immunity upon
      gene gun DNA vaccination and that broad Ag expression rather than DC-restricted
      approaches are necessary for induction of complete immune responses.

PMID- 16585549
TI  - Targeted disruption of CD38 accelerates autoimmune diabetes in NOD/Lt mice by
      enhancing autoimmunity in an ADP-ribosyltransferase 2-dependent fashion.
AB  - Ubiquitously expressed CD38 and T cell-expressed ADP-ribosyltransferase 2 (ART2)
      are ectoenzymes competing for NAD substrate. CD38 exerts pleiotropic actions in
      hemopoietic and nonhemopoietic compartments via effects on calcium mobilization.
      ART2 is an ADP-ribosyltransferase on naive CD4+ and CD8+ T cells. ART2-catalyzed
      ADP-ribosylation of the P2X7 purinoreceptor elicits apoptosis. Transfer of a
      genetically disrupted CD38 allele into the autoimmune diabetes-prone NOD/Lt
      background accelerated diabetes onset in both sexes, whereas transfer of a
      disrupted ART2 complex had no effect. However, the fact that the accelerated
      pathogenesis mediated by CD38 deficiency required ART2 activity was demonstrated
      by combining both ART2 and CD38 deficiencies. Reciprocal bone marrow
      reconstitution studies demonstrated accelerated diabetes only when CD38-deficient
      bone marrow was transferred into CD38-deficient recipients. Neither decreases in
      beta cell function nor viability were indicated. Rather, the balance between T
      effectors and T-regulatory cells was disturbed in CD38-deficient but ART2-intact
      NOD mice. In these mice, significant reductions in total viable CD8+ T cells were
      observed. This was accompanied by an age-dependent increase in a diabetogenic CD8
      clonotype. This in turn correlated with impaired T-regulatory development (10
      fold reduction in Foxp3 mRNA expression). These changes were corrected when CD38
      deficiency was combined with ART2 deficiency. Both ART2-deficient and CD38/ART2
      combined deficient T cells were resistant to NAD-induced killing in vitro,
      whereas CD38-deficient but ART2-intact T cells showed increased sensitivity,
      particularly the CD4+ CD25+ subset. Unexpectedly, diabetes development in the
      combined CD38/ART2 stock was strongly suppressed, possibly through epistatic
      interactions between genes linked to the targeted CD38 on Chromosome 5 and the
      ART2 complex on Chromosome 7.

PMID- 16585551
TI  - Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that
      prevent experimental autoimmune diabetes.
AB  - Insulin, an autoantigen in type 1 diabetes, when administered mucosally to
      diabetes-prone NOD mice induces regulatory T cells (T(reg)) that protect against
      diabetes. Compared with protein, Ag encoded as DNA has potential advantages as a
      therapeutic agent. We found that intranasal vaccination of NOD mice with plasmid
      DNA encoding mouse proinsulin II-induced CD4+ T(reg) that suppressed diabetes
      development, both after adoptive cotransfer with "diabetogenic" spleen cells and
      after transfer into NOD mice given cyclophosphamide to accelerate diabetes onset.
      In contrast to prototypic CD4+ CD25+ T(reg), CD4+ T(reg) induced by proinsulin
      DNA were both CD25+ and CD25- and not defined by markers such as glucocorticoid
      induced TNFR-related protein (GITR), CD103, or Foxp3. Intriguingly, despite
      induction of T(reg) and reduced islet inflammation, diabetes incidence in
      proinsulin DNA-treated mice was unchanged. However, diabetes was prevented when
      DNA vaccination was performed under the cover of CD40 ligand blockade, known to
      prevent priming of CTL by mucosal Ag. Thus, intranasal vaccination with
      proinsulin DNA has therapeutic potential to prevent diabetes, as demonstrated by
      induction of protective T(reg), but further modifications are required to improve
      its efficacy, which could be compromised by concomitant induction of pathogenic
      immunity.

PMID- 16585552
TI  - Selective requirement of p38alpha MAPK in cytokine-dependent, but not antigen
      receptor-dependent, Th1 responses.
AB  - The role of the p38 MAPK pathway in Th1 development has been controversial,
      because indirect manipulations of either upstream p38 activators or modifiers of
      p38 activity have had variable effects on IFN-gamma production in CD4+ T cells.
      Uncertainties regarding the specificity of pharmacologic inhibition or p38
      dominant negative mutants diminish the strength of conclusions about the role of
      the p38alpha isoform in Th1 development. Also, the effects of some upstream p38
      activators, such as MAPK kinase 3, on Th1 development are not as strong as the
      effects of other manipulations, such as the expression of a dominant negative p38
      mutant. Finally, embryonic lethality has prevented a direct examination of
      p38alpha-deficient T cells. To test the requirement for p38alpha in Th1
      differentiation, we generated Ag-specific p38alpha+/- and p38alpha-/- CD4+ T
      cells using RAG2-/- blastocyst complementation and retroviral expression of the
      DO11.10 TCR. IFN-gamma production in response to TCR signaling is normal in
      p38alpha-/- T cells cultured in Th1 conditions, implying normal Th1 development.
      However, p38alpha-/- Th1 cells have a much greater defect in IFN-gamma secretion
      stimulated by IL-12/IL-18 compared with TCR-induced IFN-gamma secretion. These
      results suggest that the activity of p38alpha in Th1 cells is relatively
      restricted to acting in one of two alternative pathways (i.e., cytokine induced)
      that can induce the production of IFN-gamma in differentiated Th1 cells, but that
      p38alpha is not required for the process of Th1 commitment and development
      itself.

PMID- 16585553
TI  - MHC class II expression identifies functionally distinct human regulatory T
      cells.
AB  - It has been known for decades that circulating human CD4 cells can express
      functional MHC class II molecules that induce T cell nonresponsiveness with Ag
      presentation. Because there is significant expression of MHC class II (MHC-II)
      determinants (DR) on a subpopulation CD4+ CD25(high) regulatory T cells (Treg),
      we examined the function of CD4 cells expressing MHC-DR. We demonstrate that MHC
      II expression on human CD4+ CD25(high) T cells identifies a functionally distinct
      population of Treg that induces early contact-dependent suppression that is
      associated with high Foxp3 expression. In striking contrast, MHC-II- CD4+
      CD25(high) Treg induce early IL-4 and IL-10 secretion and a late Foxp3-associated
      contact-dependent suppression. The DR expressing CD25(high) Treg express higher
      levels of Foxp3 message and protein, compared with the DR- CD25(high) Treg
      population. Direct single-cell cloning of CD4+ CD25(high) Treg revealed that,
      regardless of initial DR expression, ex vivo expression of CD25(high), and not
      DR, predicted which clones would exhibit contact-dependent suppression, high
      levels of Foxp3 message, and an increased propensity to become constitutive for
      DR expression. Thus, the direct ex vivo expression of MHC-II in the context of
      CD25(high) identifies a mature, functionally distinct regulatory T cell
      population involved in contact-dependent in vitro suppression.

PMID- 16585554
TI  - Accelerated memory cell homeostasis during T cell depletion and approaches to
      overcome it.
AB  - Partial T cell depletion is used in solid organ transplantation as a valuable
      strategy of peritransplant induction immunosuppression. Using a murine cardiac
      allograft model, we recently demonstrated that this led to lymphopenia-induced
      (homeostatic) proliferation among the residual nondepleted lymphocytes. Rather
      than promoting tolerance, peritransplant T cell-depleting Abs actually resulted
      in resistance to tolerance induction by costimulatory blockade. In this study we
      show that memory T cells predominate shortly after subtotal lymphodepletion due
      to two distinct mechanisms: relative resistance to depletion and enhanced
      homeostatic proliferation. In contrast, regulatory cells (CD4+ CD25+ Foxp3+) are
      depleted as efficiently as nonregulatory cells and exhibit reduced homeostatic
      expansion compared with memory cells. The resistance to tolerance induction seen
      with subtotal T cell depletion can be overcome in two different ways: first, by
      the adoptive transfer of additional unprimed regulatory cells at the time of
      transplant, and second, by the adjunctive use of nondepleting anti-CD4 and anti
      CD8 mAbs, which effectively block homeostatic expansion. We conclude that the
      resistance to tolerance induction seen after subtotal lymphocyte depletion can be
      attributed to alterations in the balance of naive, memory, and regulatory T
      cells. These data have clinically relevant implications related to the
      development of novel strategies to overcome resistance to tolerance.

PMID- 16585555
TI  - DOCK2 is required in T cell precursors for development of Valpha14 NK T cells.
AB  - Mouse CD1d-restricted Valpha14 NKT cells are a unique subset of lymphocytes,
      which play important roles in immune regulation, tumor surveillance and host
      defense against pathogens. DOCK2, a mammalian homolog of Caenorhabditis elegans
      CED-5 and Drosophila melanogaster myoblast city, is critical for lymphocyte
      migration and regulates T cell responsiveness through immunological synapse
      formation, yet its role in Valpha14 NKT cells remains unknown. We found that
      DOCK2 deficiency causes marked reduction of Valpha14 NKT cells in the thymus,
      liver, and spleen. When alpha-galactosylceramide (alpha-GalCer), a ligand for
      Valpha14 NKT cells, was administrated, cytokine production was scarcely detected
      in DOCK2-deficient mice, suggesting that DOCK2 deficiency primarily affects
      generation of Valpha14 NKT cells. Supporting this idea, staining with CD1d/alpha
      GalCer tetramers revealed that CD44- NK1.1- Valpha14 NKT cell precursors are
      severely reduced in the thymuses of DOCK2-deficient mice. In addition, studies
      using bone marrow chimeras indicated that development of Valpha14 NKT cells
      requires DOCK2 expression in T cell precursors, but not in APCs. These results
      indicate that DOCK2 is required for positive selection of Valpha14 NKT cells in a
      cell-autonomous manner, thereby suggesting that avidity-based selection also
      governs development of this unique subset of lymphocytes in the thymus.

PMID- 16585557
TI  - Dendritic cell differentiation and immune tolerance to insulin-related peptides
      in Igf2-deficient mice.
AB  - There is some evidence that insulin-like growth factor 2 (IGF-2) may intervene in
      the control of T cell differentiation. To further study the immunoregulatory
      function of this growth factor, we analyzed the immune system of Igf2-/- mice.
      Phenotypically, some immunological parameters such as lymphoid organ morphology
      and cellularity were unaltered in Igf2-/- mice, but an increase of CD8+ cells and
      a decrease of B220+ cells were observed in spleen. In vitro, the development of
      bone marrow-derived dendritic cells was affected by the absence of Igf2
      expression. After maturation, a higher percentage of immature dendritic cells was
      observed in Igf2-/- population, together with a secondary decrease in allogenic T
      cell proliferation. Activation of T cells was also affected by the lack of
      expression of this growth factor. The profile of B cell response in mutant mice
      immunized with IGF-2 evidenced a T-dependent profile of anti-IGF-2 Abs that was
      absent in Igf2+/+ mice. The influence of IGF-2 upon tolerance to insulin was also
      assessed in this model, and this showed that IGF-2 also intervenes in tolerance
      to insulin. The presence of a T-dependent response in Igf2-deficient mice should
      allow cloning of specific "forbidden" T CD4+ lymphocytes directed against IGF-2,
      as well as further investigation of their possible pathogenic properties against
      insulin family.

PMID- 16585556
TI  - CD48 stimulation by 2B4 (CD244)-expressing targets activates human NK cells.
AB  - Human NK cells can be activated by a variety of different cell surface receptors.
      Members of the SLAM-related receptors (SRR) are important modulators of NK cell
      activity. One interesting feature of the SRR is their homophilic interaction,
      combining receptor and ligand in the same molecule. Therefore, SRR cannot only
      function as activating NK cell receptors, but also as activating NK cell ligands.
      2B4 (CD244) is the only SRR that does not show homophilic interaction. Instead,
      2B4 is activated by binding to CD48, a GPI-anchored surface molecule that is
      widely expressed in the hemopoietic system. In this study, we show that 2B4 also
      can function as an activating NK cell ligand. 2B4-expressing target cells can
      efficiently stimulate NK cell cytotoxicity and IFN-gamma production. Using
      soluble receptor fusion proteins and SRR-transfected cells, we show that 2B4 does
      not bind to any other SRR expressed on NK cells, but only interacts with CD48.
      Lysis of 2B4-expressing target cells can be blocked by anti-CD48 Abs and
      triggering of CD48 in a redirected lysis assay can stimulate NK cell
      cytotoxicity. This demonstrates that 2B4 can stimulate NK cell cytotoxicity and
      cytokine production by interacting with NK cell expressed CD48 and adds CD48 to
      the growing number of activating NK cell receptors.

PMID- 16585558
TI  - Conditioning of Langerhans cells induced by a primary CD8 T cell response to self
      antigen in vivo.
AB  - Using a previously described model of autoimmune skin disease, we addressed the
      question of how CD8 T cell responsiveness to self-Ag is regulated during chronic
      inflammation. In this model, CD8 T cells expand and induce tissue pathology
      directed at an epidermal self-Ag. However, we show here that this primary CD8 T
      cell response prevented subsequent expansion of a second CD8 T cell population
      with the same specificity. This lack of T cell accumulation was not due to Ag
      elimination, nor was it due to competition between the two T cell populations.
      However, skin-specific dendritic cells that present Ag in this model--Langerhans
      cells--underwent significant phenotypic changes associated with a compromised
      ability to stimulate naive T cells. Our study suggests that conditioning of
      dendritic cells may play a role in maintaining unresponsiveness to self-Ag during
      chronic inflammation.

PMID- 16585559
TI  - NF-kappaB-inducing kinase is involved in the activation of the CD28 responsive
      element through phosphorylation of c-Rel and regulation of its transactivating
      activity.
AB  - Previous evidence suggested that NF-kappaB-inducing kinase (NIK) might regulate
      IL-2 synthesis. However, the molecular mechanism is not understood. In this
      study, we show that NIK is involved in CD3 plus CD28 activation of IL-2
      transcription. Splenic T cells from aly/aly mice (that have a defective NIK
      protein) have a severe impairment in IL-2 and GM-CSF but not TNF secretion in
      response to CD3/CD28. This effect takes place at the transcriptional level as
      overexpression of alyNIK inhibits IL-2 promoter transcription. NIK activates the
      CD28 responsive element (CD28RE) of the IL-2 promoter and strongly synergizes
      with c-Rel in this activity. We found that NIK interacts with the N-terminal
      domain of c-Rel, mapping this interaction to aa 771-947 of NIK. Moreover, NIK
      phosphorylates the c-Rel C-terminal transactivation domain (TAD) and induces Gal4
      c-Rel-transactivating activity. Anti-CD28 activated Gal4-c-Rel transactivation
      activity, and this effect was inhibited by a NIK-defective mutant. Deletion
      studies mapped the region of c-Rel responsive to NIK in aa 456-540. Mutation of
      several serines, including Ser471, in the TAD of c-Rel abrogated the NIK
      enhancing activity of its transactivating activity. Interestingly, a Jurkat
      mutant cell line that expresses one of the mutations of c-Rel (Ser471Asn) has a
      severe defect in IL-2 and CD28RE-dependent transcription in response to CD3/CD28
      or to NIK. Our results support that NIK may be controlling CD28RE-dependent
      transcription and T cell activation by modulating c-Rel phosphorylation of the
      TAD. This leads to more efficient transactivation of genes which are dependent on
      CD28RE sites where c-Rel binds such as the IL-2 promoter.

PMID- 16585560
TI  - Nitric oxide protects macrophages from hydrogen peroxide-induced apoptosis by
      inducing the formation of catalase.
AB  - We investigated the cytoprotective effect of NO on H2O2-induced cell death in
      mouse macrophage-like cell line RAW264. H2O2-treated cells showed apoptotic
      features, such as activation of caspase-9 and caspase-3, nuclear fragmentation,
      and DNA fragmentation. These apoptotic features were significantly inhibited by
      pretreatment for 24 h with NO donors, sodium nitroprusside and 1-hydroxy-2-oxo
      3,3-bis-(2-aminoethyl)-1-triazene, at a low nontoxic concentration. The
      cytoprotective effect of NO was abrogated by the catalase inhibitor 3-amino-1,2,4
      triazole but was not affected by a glutathione synthesis inhibitor, L-buthionine
      (S,R)-sulfoximine. NO donors increased the level of catalase and its activity in
      a concentration-dependent manner. Cycloheximide, a protein synthesis inhibitor,
      inhibited both the NO-induced increase in the catalase level and the
      cytoprotective effect of NO. These results indicate that NO at a low
      concentration protects macrophages from H2O2-induced apoptosis by inducing the
      production of catalase.

PMID- 16585562
TI  - Phospholipase Cgamma2 dosage is critical for B cell development in the absence of
      adaptor protein BLNK.
AB  - B cell linker (BLNK) protein and phospholipase Cgamma2 (PLCgamma2) are components
      of the BCR signalosome that activate calcium signaling in B cells. Mice lacking
      either molecule have a severe but incomplete block in B lymphopoiesis. In this
      study, we generated BLNK-/- PLCgamma2-/- mice to examine the effect of
      simultaneous disruption of both molecules on B cell development. We showed that
      BLNK-/- PLCgamma2-/- mice had compounded defects in B cell maturation compared
      with either single mutant, suggesting that these two molecules cooperatively or
      synergistically signaled B lymphopoiesis. However, Ig H chain allelic exclusion
      was maintained in single and double mutants, indicating that signals propagated
      by BLNK and PLCgamma2 were not involved in this process. Interestingly, in the
      absence of BLNK, B cell development was dependent on plcgamma2 gene dosage. This
      was evidenced by the proportionate decrease in splenic B cell population and
      increase in bone marrow surface pre-BCR+ cells in PLCgamma2-diploid, -haploid,
      and -null animals. Intracellular calcium signaling and ERK activation in response
      to BCR engagement were also proportionately decreased and delayed, respectively,
      with stepwise reduction of plcgamma2 dosage in a BLNK(null) background. Thus,
      these data indicate the importance of BLNK not only as a conduit to specifically
      channel BCR-signaling pathways and as a scaffold for the assembling of
      macromolecular complex, but also as an efficient aggregator or concentrator of
      PLCgamma2 molecules to effect optimal signaling for B cell generation and
      activation.

PMID- 16585561
TI  - Direct stimulation of T cells by type I IFN enhances the CD8+ T cell response
      during cross-priming.
AB  - Type I IFN (IFN-alphabeta), which is produced rapidly in response to infection,
      plays a key role in innate immunity and also acts as a stimulus for the adaptive
      immune response. We have investigated how IFN-alphabeta induces cross-priming,
      comparing CD8+ T cell responses generated against soluble protein Ags in the
      presence or absence of IFN-alphabeta. Injection of IFN-alpha was found to prolong
      the proliferation and expansion of Ag-specific CD8+ T cells, which was associated
      with marked up-regulation of IL-2 and IL-15 receptors on Ag-specific cells and
      expression of IL-15 in the draining lymph node. Surprisingly, neither IL-2 nor IL
      15 was required for IFN-alpha-induced cross-priming. Conversely, expression of
      the IFN-alphabetaR by T cells was shown to be necessary for effective stimulation
      of the response by IFN-alpha. The finding that T cells represent direct targets
      of IFN-alphabeta-mediated stimulation reveals an additional mechanism by which
      the innate response to infection promotes adaptive immunity.

PMID- 16585563
TI  - Motif inference reveals optimal CTL epitopes presented by HLA class I alleles
      highly prevalent in southern Africa.
AB  - HIV-specific CTL play a central role in immune control of HIV. The basis for
      understanding the success or failure of this immune response requires
      identification of the specific epitopes targeted by CTL. However, in populations
      most severely affected by the global epidemic, this fundamental knowledge is
      hindered by the lack of characterization of many of the HLA class I alleles
      highly prevalent in such populations. Overall, the peptide-binding motif has been
      determined for a small minority (9%) of HLA class I alleles, with a strong bias
      toward those alleles prevalent in Caucasoid populations. These studies therefore
      set out to define, in a South African Zulu/Xhosa population at the epicenter of
      the epidemic, the epitopes presented by alleles highly prevalent, but for which
      the peptide-binding motif had not been characterized. Using a method of motif
      inference, epitopes presented by four such alleles prevalent in the Zulu/Xhosa
      population of Durban, South Africa, namely, B*3910, B*4201, B*8101, and Cw*1801,
      are described. Importantly, this approach may additionally facilitate
      optimization of epitopes in certain instances where conflicting reports in the
      literature exist regarding the peptide-binding motif, such as for HLA-A*2902,
      also highly prevalent in southern African populations. These data indicate that
      the previously anomalous position of HLA-A*2902 among HLA-A alleles, outside any
      recognized HLA-A supertype, is artifactual, and the true position of the A*2902
      motif overlaps those of the A1 and A24 supertypes.

PMID- 16585564
TI  - Identification of memory B cells using a novel transgenic mouse model.
AB  - Memory B cells help to protect the host from invading pathogens by maintaining
      persistent levels of Ag-specific serum Ab and generating rapid Ab responses upon
      re-exposure to Ag. Unambiguous identification of memory B cells has been a major
      obstacle to furthering our knowledge concerning both the development of B cell
      memory and secondary Ab responses due to an absence of specific cell surface
      markers. Germinal centers (GCs) are thought to be the major site of Ig
      hypermutation and Ag-driven selection of memory B cells. To develop a model that
      would identify GC-derived memory B cells, we generated transgenic mice that
      expressed cre recombinase in a GC-specific fashion. Interbreeding these mice with
      the cre-reporter strain, ROSA26R, produced progeny in which beta-galactosidase
      (beta-gal) was permanently expressed in B cells of the GC-memory pathway.
      Analysis following immunization with (4-hydroxy-3-nitrophenyl)acetyl coupled to
      chicken gamma globulin showed that long-lived beta-gal+ B cells exclusively
      contained somatically mutated lambda1 V regions and were capable of producing Ag
      specific Ab-forming cell (AFC) responses that were >100-fold higher than those
      afforded by beta-gal- B cells following adoptive transfer to naive hosts.
      Secondary challenge of immune mice showed that only approximately 20% of
      secondary AFCs expressed beta-gal. Interestingly, we found that somatic
      hypermutation of rearranged lambda1 V regions within secondary AFCs showed a
      strong correlation with beta-gal expression, suggesting that nonmutated B cells
      contribute significantly to secondary Ab responses. This model should provide
      useful insights into memory B cell development, maintenance, and differentiation
      following immunization or pathogenic infection.

PMID- 16585565
TI  - IFN-gamma acts on T cells to induce NK cell mobilization and accumulation in
      target organs.
AB  - The mechanism(s) that regulates NK cell mobilization and the significance of this
      process to NK cell activity are unknown. After Con A-induced hepatitis, NK cells
      are mobilized from the spleen and bone marrow into the periphery in an IFN-gamma
      dependent fashion. Intraperitoneal administration of IFN-gamma stimulates the
      mobilization of NK cells into the circulation, but not their cell death or
      proliferation. Increased number of circulating NK cells was coupled with their
      accumulation in the peritoneum, liver, and tumor-bearing lung tissue.
      Furthermore, increased number of NK cells in the lung reduced metastasis of Lewis
      lung carcinoma cells (3LL cell line) resulting in significantly extended NK
      dependent survival. Mobilization of NK cells was specific and required the
      presence of T cells. Moreover, mobilization and migration of spleen NK cells in
      response to IFN-gamma treatment is dependent on the chemokine receptor CXCR3.
      Mechanistic insights regarding the role of IFN-gamma in the regulation of NK cell
      mobilization and their accumulation at sites of tumor metastasis may lead to the
      development of novel immunotherapy for cancer.

PMID- 16585566
TI  - Adaptive islet-specific regulatory CD4 T cells control autoimmune diabetes and
      mediate the disappearance of pathogenic Th1 cells in vivo.
AB  - Adaptive regulatory T cells that develop from naive CD4 cells in response to
      exposure to Ag can act as immunotherapeutic agents to control immune responses.
      We show that effectors generated from murine islet-specific CD4 cells by TCR
      stimulation with IL-2 and TGF-beta1 have potent suppressive activity. They
      prevent spontaneous development of type 1 diabetes in NOD mice and inhibit
      development of pancreatic infiltrates and disease onset orchestrated by Th1
      effectors. These regulatory T cells do not require innate CD25+ regulatory cells
      for generation or function, nor do they share some characteristics typically
      associated with them, including expression of CD25. However, the adaptive
      population does acquire the X-linked forkhead/winged helix transcription factor,
      FoxP3, which is associated with regulatory T cell function and maintains
      expression in vivo. One mechanism by which they may inhibit Th1 cells is via FasL
      dependent cytotoxicity, which occurs in vitro. In vivo, they eliminate Th1 cells
      in lymphoid tissues, where Fas/FasL interactions potentially play a role because
      Th1 cells persist when this pathway is blocked. The results suggest that adaptive
      regulatory CD4 cells may control diabetes in part by impairing the survival of
      islet-specific Th1 cells, and thereby inhibiting the localization and response of
      autoaggressive T cells in the pancreatic islets.

PMID- 16585567
TI  - Early growth response gene 1 provides negative feedback to inhibit entry of
      progenitor cells into the thymus.
AB  - The size of the thymus can be greatly influenced by changes in the small number
      of early progenitors in the thymus. However, it is not known whether thymic
      cellularity feeds back to regulate the recruitment, survival, and expansion of
      progenitors. The transcription factor early growth response gene 1 (Egr1) has
      been implicated in controlling proliferation and survival in many cell types. We
      have previously shown that mice deficient in Egr1 have increased thymic
      cellularity. We now show that Egr1 regulates a negative feedback signal that
      controls the entry of cells into the thymus. Egr1-deficient mice have higher
      percentages of early T lineage progenitors in the thymus, yet Egr1-deficient mice
      have normal numbers of myelolymphoid progenitors in the bone marrow, and Egr1
      deficient thymocytes show normal rates of apoptosis and proliferation at all
      stages of development. Evidence from mixed bone marrow chimeras shows that the
      ability of Egr1 to control progenitor recruitment is mediated by bone marrow
      derived cells, but is not cell autonomous. Furthermore, Egr1-deficient thymuses
      have increased P-selectin expression. The data suggest that Egr1 mediates a
      feedback mechanism whereby the number of resident double negative thymocytes
      controls the entry of new progenitors into the thymus by regulating P-selectin
      expression on thymic endothelial cells.

PMID- 16585568
TI  - Control of autoimmune myocarditis and multiorgan inflammation by glucocorticoid
      induced TNF receptor family-related protein(high), Foxp3-expressing CD25+ and
      CD25- regulatory T cells.
AB  - Anomalies of naturally occurring CD4+ regulatory T cells (Treg) cause severe
      autoimmune/inflammatory diseases in humans and rodents. The transcription factor
      Foxp3 is currently the most specific marker for natural CD4+ Treg, but it would
      be useful if other Treg markers, particularly cell surface molecules, could be
      elucidated. We demonstrate in this study that the vast majority of Foxp3
      expressing CD4+ T cells (whether CD25+ or CD25-) show constitutive high-level
      expression of glucocorticoid-induced TNFR family-related gene/protein (GITR).
      Transfer of T cell or thymocyte suspensions depleted of GITR(high) cells produces
      in BALB/c nude mice a wider spectrum and more severe forms of autoimmune diseases
      than does transfer of similar cell suspensions depleted of CD25+ CD4+ T cells
      only. Notably, mice that receive cells depleted of GITR(high) populations develop
      severe multiorgan inflammation that includes fatal autoimmune myocarditis
      resembling giant cell myocarditis in humans, accompanying high-titer anti-myosin
      autoantibodies. Similar transfer of GITR(high)-depleted cells from prediabetic
      NOD mice to NOD-SCID mice accelerates the development of diabetes and induces
      skeletal muscle myositis and other autoimmune/inflammatory diseases. We conclude
      that GITR(high), Foxp3-expressing natural Treg, containing both CD25+ and CD25-
      cell populations, contribute to preventing a variety of autoimmune/inflammatory
      diseases, and depletion of these cells allows the activation of even weak or rare
      autoreactive T cells yielding widespread severe autoimmune disease. Diseases
      induced in this way include many which have been suspected of an autoimmune
      etiology in humans without much evidence. GITR(high), Foxp3-expressing natural
      Treg represent a potential target for the treatment and prevention of these
      diseases.

PMID- 16585569
TI  - Immunosensitization of tumor cells to dendritic cell-activated immune responses
      with the proteasome inhibitor bortezomib (PS-341, Velcade).
AB  - Proteasome inhibition results in proapoptotic changes in cancer cells, which may
      make them more sensitive to immune effector cells. We established a murine model
      to test whether the proteasome inhibitor bortezomib could sensitize established
      B16 melanoma tumors to dendritic cell (DC)-activated immune effector cells. Day 3
      established s.c. B16 tumors had significantly decreased tumor outgrowth when
      treated with a combination of bortezomib and DC, regardless of whether the DC
      were loaded or not with a tumor Ag. In vivo Ab-depletion studies demonstrated
      that the effector cells were NK and CD8+ cells, but not CD4+ cells. NF-kappaB
      nuclear transcription factor assay and gene-expression profiling of B16 treated
      with bortezomib was consistent with inhibition of NF-kappaB target genes leading
      to a proapoptotic phenotype. In vitro lytic assays demonstrated that TNF-alpha,
      but not perforin, Fas-ligand, or TRAIL, was responsible for bortezomib-sensitized
      B16 cytotoxicity. In conclusion, the proteasome inhibitor bortezomib can
      pharmacologically sensitize tumor cells to the lytic effects of DC-activated
      immune effector cells.

PMID- 16585570
TI  - Identification of novel Th2-associated genes in T memory responses to allergens.
AB  - Atopic diseases are associated with hyperexpression of Th2 cytokines by allergen
      specific T memory cells. However, clinical trials with recently developed Th2
      inhibitors in atopics have proven disappointing, suggesting underlying
      complexities in atopy pathogenesis which are not satisfactorily explained via the
      classical Th1/Th2 paradigm. One likely possibility is that additional Th2
      associated genes which are central to disease pathogenesis remain unidentified.
      The aim of the present study was to identify such novel Th2-associated genes in
      recall responses to the inhalant allergen house dust mite. In contrast to earlier
      human microarray studies in atopy which focused on mitogen-activated T cell lines
      and clones, we concentrated on PBMC-derived primary T cells stimulated under more
      physiological conditions of low dose allergen exposure. We screened initially for
      allergen-induced gene activation by microarray, and validated novel genes in
      independent panels of subjects by quantitative RT-PCR. Kinetic analysis of
      allergen responses in PBMC revealed an early wave of novel atopy-associated genes
      involved in signaling which were coexpressed with IL-4 and IL-4R, followed by a
      later wave of genes encoding the classical Th2 effector cytokines. We further
      demonstrate that these novel activation-associated Th2 genes up-regulate in
      response to another atopy-associated physiological stimulus bacterial
      superantigen, but remain quiescent in nonphysiological responses in primary T
      cells or cell lines driven by potent mitogens, which may account for their
      failure to be detected in earlier microarray studies.

PMID- 16585571
TI  - Engagement of CD28 outside of the immunological synapse results in up-regulation
      of IL-2 mRNA stability but not IL-2 transcription.
AB  - During T cell activation by APC, CD28 is colocalized with TCR in the central
      supramolecular activation cluster (cSMAC) region of the immunological synapse.
      CD28 signaling through PI3K results in the recruitment of protein kinase C
      (PKC)theta to the cSMAC, activation of NF-kappaB, and induction of IL-2
      transcription. These results suggest that localized engagement of CD28 within the
      cSMAC may be required for CD28 activation and/or signal integration with TCR
      signals. To test this model we have examined the mechanism of CD28-mediated
      induction of IL-2 secretion when CD28 is engaged outside of the immunological
      synapse. CD4 T cells were stimulated with Ag presented by B7-negative APC and
      CD28 costimulation was provided in trans by anti-CD28-coated beads or by class II
      negative, B7-positive cells. We show that induction of IL-2 secretion under these
      conditions did not require expression of PKCtheta and did not induce NF-kappaB
      activation or IL-2 transcription. In contrast, CD28 costimulation in trans did
      induce IL-2 mRNA stability, accounting for the up-regulation of IL-2 secretion.
      These data indicate that the ability of CD28 to up-regulate IL-2 transcription
      requires colocalization of TCR and CD28 at the plasma membrane, possibly within
      the cSMAC of the immunological synapse. In contrast, the ability of CD28 to
      promote IL-2 mRNA stability can be transduced from a distal site from the TCR,
      suggesting that signal integration occurs downstream from the plasma membrane.
      These data support the potential role of trans costimulation in tumor and
      allograft rejection, but limit the potential functional impact that trans
      costimulation may have on T cell activation.

PMID- 16585572
TI  - Selective regulation of IL-10 signaling and function by zymosan.
AB  - Balanced activity of pro- and anti-inflammatory cytokines during innate immune
      responses is required to allow effective host defense while avoiding tissue
      damage and autoimmunity. Induction of cytokine production after recognition of
      pathogen-associated molecular patterns (PAMPs) by innate immune cells has been
      well demonstrated, but modulation of cytokine function by PAMPs is not well
      understood. In this study we show that stimulation of macrophages with zymosan,
      which contains PAMPs derived from yeast, rapidly extinguished macrophage
      responses to IL-10, a suppressive cytokine that limits inflammatory tissue damage
      but also compromises host defense. The mechanism of inhibition involved protein
      kinase Cbeta and internalization of IL-10R, and was independent of TLR2 and
      phagocytosis. Inhibition of IL-10 signaling and function required direct contact
      with zymosan, and cells in an inflammatory environment that had not contacted
      zymosan remained responsive to the paracrine activity of zymosan-induced IL-10.
      These results reveal a mechanism that regulates IL-10 function such that
      antimicrobial functions of infected macrophages are not suppressed, but the
      activation of surrounding noninfected cells and subsequent tissue damage are
      limited. The fate of individual cells in an inflammatory microenvironment is thus
      specified by dynamic interactions among host cells, microbes, and cytokines that
      determine the balance between protection and pathology.

PMID- 16585573
TI  - Coordination of NF-kappaB and NFAT antagonism by the forkhead transcription
      factor Foxd1.
AB  - Forkhead transcription factors play critical roles in the maintenance of immune
      homeostasis. In this study, we demonstrate that this regulation most likely
      involves intricate interactions between the forkhead family members and
      inflammatory transcription factors: the forkhead member Foxd1 coordinates the
      regulation of the activity of two key inflammatory transcription factors, NF-AT
      and NF-kappaB, with Foxd1 deficiency resulting in multiorgan, systemic
      inflammation, exaggerated Th cell-derived cytokine production, and T cell
      proliferation in autologous MLRs. Foxd1-deficient T cells possess increased
      activity of both NF-AT and NF-kappaB: the former correlates with the ability of
      Foxd1 to regulate casein kinase 1, an NF-AT inhibitory kinase; the latter with
      the ability of Foxd1 to regulate Foxj1, which regulates the NF-kappaB inhibitory
      subunit IkappaB beta. Thus, Foxd1 modulates inflammatory reactions and prevents
      autoimmunity by directly regulating anti-inflammatory regulators of the NF-AT
      pathway, and by coordinating the suppression of the NF-kappaB pathway via Foxj1.
      These findings indicate the presence of a general network of forkhead proteins
      that enforce T cell quiescence.

PMID- 16585574
TI  - IFN-gamma enhances production of nitric oxide from macrophages via a mechanism
      that depends on nucleotide oligomerization domain-2.
AB  - Pattern recognition receptors are central to the responsiveness of various
      eukaryotic cell types when they encounter pathogen-associated molecular patterns.
      IFN-gamma is a cytokine that is elevated in humans and other animals with
      bacterial infection and enhances the LPS-induced production of antibacterial
      mediators by macrophages. Mice lacking the pattern recognition receptor, TLR4,
      respond very poorly to stimulation by LPS, but administration of IFN-gamma has
      been described as restoring apparent sensitivity to this stimulatory ligand. In
      this study, we show that IFN-gamma primes murine macrophages stimulated by crude
      LPS preparations to produce the antibacterial mediator NO, a proportion of which
      is independent of TLRs 2 and 4. This response is lost in tlr4-/- IFN-gamma-primed
      murine macrophages when the LPS preparation is highly purified. NO is also
      induced if chemically synthesized muramyl dipeptide, an intermediate in the
      biosynthesis of peptidoglycan, is used to stimulate macrophages primed with IFN
      gamma. This is absolutely dependent on the presence of a functional nucleotide
      oligomerization domain-2 (NOD-2) protein. IFN-gamma increases NOD-2 expression
      and dissociates this protein from the actin cytoskeleton within the cell. IFN
      gamma priming of macrophages therefore reveals a key proinflammatory role for NOD
      2. This study also shows that the effect of IFN-gamma in restoring inflammatory
      responses to gram-negative bacteria or bacterial products in mice with defective
      TLR4 signaling is likely to be due to a response to peptidoglycan, not LPS.

PMID- 16585575
TI  - Differential T cell-mediated regulation of CD23 (Fc epsilonRII) in B cells and
      follicular dendritic cells.
AB  - Differences in murine follicular dendritic cells (FDC)-CD23 expression under Th1
      vs Th2 conditions prompted the hypothesis that T cells help regulate the
      phenotype of FDCs. FDCs express CD40, suggesting that T cell-CD40L and
      lymphokines may be involved in regulating FDC-CD23. To test this, highly enriched
      FDCs were incubated with CD40L trimer or anti-CD40 to mimic T cell signaling in
      the presence of IFN-gamma or IL-4. Surface expression of CD23 was determined by
      flow cytometry, whereas mRNA levels of CD23 and its isoforms CD23a and CD23b were
      independently measured by quantitative PCR. When FDCs were incubated with either
      CD40L trimer or agonistic anti-CD40 Ab, the expression of FDC-CD23 was increased
      both at the mRNA and protein levels. Moreover, engagement of FDC-CD40 enhanced
      mRNA levels for both CD23a and CD23b isoforms. In addition, IFN-gamma
      substantially enhanced CD23a and CD23b mRNA levels in CD40-stimulated FDCs.
      Curiously, IL-4 could also up-regulate FDC-CD23a but not -CD23b. Anti-IFN-gamma
      dramatically inhibited FDC-CD23 in mice immunized with CFA, whereas anti-IL-4 had
      only a modest inhibitory effect. In contrast with FDCs, IFN-gamma inhibited
      surface expression of murine B cell-CD23 as well as mRNA for B cell CD23a and 
      CD23b, whereas IL-4 dramatically enhanced message for both isoforms as well as
      protein expression. In short, CD23 was regulated very differently in FDCs and B
      cells. Previous studies suggest that high levels of FDC-CD23 inhibit IgE
      production, and this IFN-gamma and CD40L-mediated up-regulation of FDC-CD23 may
      explain, at least in part, why Th1 responses are associated with low IgE
      responses in vivo.

PMID- 16585576
TI  - Wip1 phosphatase-deficient mice exhibit defective T cell maturation due to
      sustained p53 activation.
AB  - The PP2C phosphatase Wip1 dephosphorylates p38 and blocks UV-induced p53
      activation in cultured human cells. Although the level of TCR-induced p38 MAPK
      activity is initially comparable between Wip1-/- and wild-type thymocytes,
      phosphatase-deficient cells failed to down-regulate p38 MAPK activity after 6 h.
      Analysis of young Wip1-deficient mice showed that they had fewer splenic T cells.
      Their thymi were smaller, contained significantly fewer cells, and failed to
      undergo age-dependent involution compared with wild-type animals. Analysis of
      thymocyte subset numbers by flow cytometry suggested that cell numbers starting
      at the double-negative (DN)4 stage are significantly reduced in Wip1-deficient
      mice, and p53 activity is elevated in cell-sorted DN4 and double-positive
      subpopulations. Although apoptosis and proliferation was normal in Wip1-/- DN4
      cells, they appeared to be in cell cycle arrest. In contrast, a significantly
      higher percentage of apoptotic cells were found in the double-positive
      population, and down-regulation of thymocyte p38 MAPK activation by anti-CD3 was
      delayed. To examine the role of p38 MAPK in early thymic subpopulations, fetal
      thymic organ cultures cultured in the presence/absence of a p38 MAPK inhibitor
      did not correct the thymic phenotype. In contrast, the abnormal thymic phenotype
      of Wip1-deficient mice was reversed in the absence of p53. These data suggest
      that Wip1 down-regulates p53 activation in the thymus and is required for normal
      alphabeta T cell development.

PMID- 16585578
TI  - STAT5-mediated signals sustain a TCR-initiated gene expression program toward
      differentiation of CD8 T cell effectors.
AB  - Poorly functional effector CD8 T cells are generated in some pathological
      situations, including responses to weakly antigenic tumors. To identify the
      molecular bases for such defective differentiation, we monitored gene expression
      in naive monoclonal CD8 T cells during responses to TCR ligands of different
      affinity. We further evaluated whether responses to weak Ags may be improved by
      addition of cytokines. Transient gene expression was observed for a cluster of
      genes in response to the weak TCR agonist. Strikingly, gene expression was
      stabilized by low dose IL-2. This IL-2-sustained gene cluster encoded notably
      transcripts for CD25, cytolytic effector molecules (granzyme B) and TNF-R family
      costimulatory molecules (glucocorticoid-induced TNF-R (GITR), OX40, and 4-1BB).
      IL-2-enhanced surface expression or function was also demonstrated in vivo for
      these genes. A constitutive active form of STAT5 mimicked the IL-2 effect by
      sustaining transcripts for the same gene cluster. Consistent with this, under
      conditions of low avidity TCR engagement and IL-2 treatment, endogenous STAT5
      binding to 4-1BB and granzyme B promoters was demonstrated by chromatin
      immunoprecipitation. This study highlights those genes for which IL-2, via STAT5
      activation, acts as a stabilizer of gene regulation initiated by TCR signals,
      contributing to the development of a complete CD8 T cell effector program.

PMID- 16585579
TI  - SUMOylation interferes with CCAAT/enhancer-binding protein beta-mediated c-myc
      repression, but not IL-4 activation in T cells.
AB  - The transcription factor C/EBPbeta transactivates the IL-4 gene in murine T
      lymphocytes and facilitates Th2 cell responses. In this study, we demonstrate
      that C/EBPbeta also acts as a repressor of T cell proliferation. By binding to
      the c-myc promoter(s), C/EBPbeta represses c-Myc expression and, therefore,
      arrests T cells in the G1 phase of the cell cycle. For C/EBPbeta-mediated
      repression, the integrity of its N-terminal transactivation domain is essential
      whereas the central regulatory domain is dispensable. This central regulatory
      domain is sumoylated in vivo which leads to an alteration of the activity of
      C/EBPbeta. Whereas sumoylation does not affect the C/EBPbeta-mediated activation
      of the IL-4 gene, it relieves its repressive effect on c-Myc expression and T
      cell proliferation. Similar to several other transcription factors, sumoylation
      redistributes nuclear C/EBPbeta and targets it to pericentric heterochromatin.
      These results suggest an important role of sumoylation in adjusting the finely
      tuned balance between proliferation and differentiation in peripheral T cells
      which is controlled by C/EBPbeta.

PMID- 16585577
TI  - In vivo recognition of ovalbumin expressed by transgenic Leishmania is determined
      by its subcellular localization.
AB  - The importance of the site of Ag localization within microbial pathogens for the
      effective generation of CD8+ T cells has been studied extensively, generally
      supporting the view that Ag secretion within infected target cells is required
      for optimal MHC class I-restricted Ag presentation. In contrast, relatively
      little is known about the importance of pathogen Ag localization for the
      activation of MHC class II-restricted CD4+ T cells, despite their clear
      importance for host protection. We have used the N-terminal targeting sequence of
      Leishmania major hydrophilic acylated surface protein B to generate stable
      transgenic lines expressing physiologically relevant levels of full-length OVA on
      the surface of metacyclic promastigotes and amastigotes. In addition, we have
      mutated the hydrophilic acylated surface protein B N-terminal acylation sequence
      to generate control transgenic lines in which OVA expression is restricted to the
      parasite cytosol. In vitro, splenic dendritic cells are able to present membrane
      localized, but not cytosolic, OVA to OVA-specific DO.11 T cells. Strikingly and
      unexpectedly, surface localization of OVA is also a strict requirement for
      recognition by OVA-specific T cells (DO.11 and OT-II) and for the development of
      OVA-specific Ab responses in vivo. However, recognition of cytosolic OVA could be
      observed with increasing doses of infection. These data suggest that, even under
      in vivo conditions, where varied pathways of Ag processing are likely to operate,
      the site of Leishmania Ag localization is an important determinant of
      immunogenicity and hence an important factor when considering the likely
      candidacy of vaccine Ags for inducing CD4+ T cell-dependent immunity.

PMID- 16585580
TI  - Nuclear magnetic resonance structure-based epitope mapping and modulation of dust
      mite group 13 allergen as a hypoallergen.
AB  - IgE-mediated allergic response involves cross-linking of IgE bound on mast cells
      by specific surface epitopes of allergens. Structural studies on IgE epitopes of
      allergens are essential in understanding the characteristics of an allergen and
      for development of specific allergen immunotherapy. We have determined the
      structure of a group 13 dust mite allergen from Dermatophagoides farinae, Der f
      13, using nuclear magnetic resonance. Sequence comparison of Der f 13 with
      homologous human fatty acid-binding proteins revealed unique surface charged
      residues on Der f 13 that may be involved in IgE binding and allergenicity. Site
      directed mutagenesis and IgE binding assays have confirmed four surface charged
      residues on opposite sides of the protein that are involved in IgE binding. A
      triple mutant of Der f 13 (E41A_K63A_K91A) has been generated and found to have
      significantly reduced IgE binding and histamine release in skin prick tests on
      patients allergenic to group 13 dust mite allergens. The triple mutant is also
      able to induce PBMC proliferation in allergic patients with indices similar to
      those of wild-type Der f 13 and shift the secretion of cytokines from a Th2 to a
      Th1 pattern. Mouse IgG serum raised using the triple mutant is capable to block
      the binding of IgE from allergic patients to wild-type Der f 13, indicating
      potential for the triple mutant as a hypoallergen for specific immunotherapy.
      Findings in this study imply the importance of surface charged residues on IgE
      binding and allergenicity of an allergen, as was also demonstrated in other major
      allergens studied.

PMID- 16585581
TI  - Cloning and characterization of mannose-binding lectin from lamprey (Agnathans).
AB  - The recognition of pathogens is mediated by a set of pattern recognition
      molecules that recognize conserved pathogen-associated molecular patterns shared
      by broad classes of microorganisms. Mannose-binding lectin (MBL) is one of the
      pattern recognition molecules and activates complement in association with MBL
      associated serine protease (MASP) via the lectin pathway. Recently, an MBL-like
      lectin was isolated from the plasma of a urochordate, the solitary ascidian. This
      ascidian lectin has a carbohydrate recognition domain, but the collagen-like
      domain was replaced by another sequence. To elucidate the origin of MBLs, the aim
      of this study is to determine the structure and function of the MBL homolog in
      lamprey, the most primitive vertebrate. Using an N-acetylglucosamine (GlcNAc)
      agarose column, MBL-like lectin (p25) was isolated from lamprey serum and cDNA
      cloning was conducted. From the deduced amino acid sequence this lectin has a
      collagenous region and a typical carbohydrate recognition domain. This lectin
      also binds mannose, glucose, and GlcNAc, but not galactose, indicating that it is
      structurally and functionally similar to the mammalian MBLs. Furthermore, it
      associated with lamprey MASPs, and the MBL-MASP activated lamprey C3 in fluid
      phase and on the surface of pathogens. In conjunction with the phylogenetic
      analysis, it seems likely that the lamprey MBL is an ortholog of the mammalian
      MBL. Because acquired immunity seems to have been established only from jawed
      vertebrates onward, the lectin complement pathway in lamprey, as one of the major
      contributors to innate immunity, plays a pivotal role in defending the body
      against microorganisms.

PMID- 16585582
TI  - Expression of endoplasmic reticulum aminopeptidases in EBV-B cell lines from
      healthy donors and in leukemia/lymphoma, carcinoma, and melanoma cell lines.
AB  - Peptide trimming in the endoplasmic reticulum (ER), the final step required for
      the generation of most HLA class I-binding peptides, implicates the concerted
      action of two aminopeptidases, ERAP1 and ERAP2. Because defects in the expression
      of these peptidases could lead to aberrant surface HLA class I expression in
      tumor cells, we quantitatively assayed 14 EBV-B cell lines and 35 human tumor
      cell lines of various lineages for: 1) expression and enzymatic activities of
      ERAP1 and ERAP2; 2) ER peptide-trimming activity in microsomes; 3) expression of
      HLA class I H chains and TAP1; and 4) surface HLA class I expression. ERAP1 and
      ERAP2 expression was detectable in all of the EBV-B and tumor cell lines, but in
      the latter it was extremely variable, sometimes barely detectable, and not
      coordinated. The expression of the two aminopeptidases corresponded well to the
      respective enzymatic activities in most cell lines. A peptide-trimming assay in
      microsomes revealed additional enzymatic activities, presumably contributed by
      other unidentified aminopeptidases sharing substrate specificity with ERAP2.
      Interestingly, surface HLA class I expression showed significant correlation with
      ERAP1 activity, but not with the activity of either ERAP2 or other unidentified
      aminopeptidases. Transfection with ERAP1 or ERAP2 of two tumor cell lines
      selected for simultaneous low expression of the two aminopeptidases resulted in
      the expected, moderate increases of class I surface expression. Thus, low and/or
      imbalanced expression of ERAP1 and probably ERAP2 may cause improper Ag
      processing and favor tumor escape from the immune surveillance.

PMID- 16585583
TI  - Transcriptional regulation of CD4 gene expression by T cell factor-1/beta-catenin
      pathway.
AB  - By interacting with MHC class II molecules, CD4 facilitates lineage development
      as well as activation of Th cells. Expression of physiological levels of CD4
      requires a proximal CD4 enhancer to stimulate basic CD4 promoter activity. T cell
      factor (TCF)-1/beta-catenin pathway has previously been shown to regulate
      thymocyte survival via up-regulating antiapoptotic molecule Bcl-xL. By both loss
      and gain of function studies, in this study we show additional function of TCF
      1/beta-catenin pathway in the regulation of CD4 expression in vivo. Mice
      deficient in TCF-1 displayed significantly reduced protein and mRNA levels of CD4
      in CD4+ CD8+ double-positive (DP) thymocytes. A transgene encoding Bcl-2 restored
      survival but not CD4 levels of TCF-1(-/-) DP cells. Thus, TCF-1-regulated
      survival and CD4 expression are two separate events. In contrast, CD4 levels were
      restored on DP TCF-1(-/-) cells by transgenic expression of a wild-type TCF-1,
      but not a truncated TCF-1 that lacks a domain required for interacting with beta
      catenin. Furthermore, forced expression of a stabilized beta-catenin, a
      coactivator of TCF-1, resulted in up-regulation of CD4. TCF-1 or stabilized beta
      catenin greatly stimulated activity of a CD4 reporter gene driven by a basic CD4
      promoter and the CD4 enhancer. However, mutation of a potential TCF binding site
      located within the enhancer abrogated TCF-1 and beta-catenin-mediated activation
      of CD4 reporter. Finally, recruitment of TCF-1 to CD4 enhancer was detected in
      wild-type but not TCF-1 null mice by chromatin-immunoprecipitation analysis.
      Thus, our results demonstrated that TCF/beta-catenin pathway enhances CD4
      expression in vivo by recruiting TCF-1 to stimulate CD4 enhancer activity.

PMID- 16585584
TI  - The bovine CD1 family contains group 1 CD1 proteins, but no functional CD1d.
AB  - The CD1 family of proteins presents lipid Ags to T cells. Human CD1a, CD1b, and
      CD1c have been shown in humans to present mycobacterial lipid Ags. Cattle, like
      humans, are a natural host of several mycobacterial pathogens. In this study, we
      describe the CD1 family of genes in cattle (Bos taurus) and provide evidence that
      B. taurus expresses CD1a, CD1e, and multiple CD1b molecules, but no CD1c and CD1d
      molecules. In mice and humans, CD1d is known to present Ag to NKT cells, a T cell
      lineage that is characterized by a limited TCR repertoire, capable of rapidly
      secreting large amounts of IFN-gamma and IL-4. In cattle, two CD1D pseudogenes
      were found and no intact CD1D genes. Consistent with this, we found complete lack
      of reactivity to a potent, cross-reactive Ag for NKT cells in mice and humans,
      alpha-galactosylceramide. Our data suggest the absence of NKT cells in cattle. It
      remains open whether other cells with the NKT-like phenotype and functions are
      present in this species. With its functional CD1A and CD1B genes, B. taurus is
      well equipped to present Ags to CD1-restricted T cells other than NKT cells.
      Cattle can be used as a model to study group 1 CD1-restricted T cell immunity,
      including its role in the defense against mycobacterial infections that occur
      naturally in this species.

PMID- 16585585
TI  - TLR3 can directly trigger apoptosis in human cancer cells.
AB  - TLRs function as molecular sensors to detect pathogen-derived products and
      trigger protective responses ranging from secretion of cytokines that increase
      the resistance of infected cells and chemokines that recruit immune cells to cell
      death that limits microbe spreading. Viral dsRNA participate in virus-infected
      cell apoptosis, but the signaling pathway involved remains unclear. In this study
      we show that synthetic dsRNA induces apoptosis of human breast cancer cells in a
      TLR3-dependent manner, which involves the molecular adaptor Toll/IL-1R domain
      containing adapter inducing IFN-beta and type I IFN autocrine signaling, but
      occurs independently of the dsRNA-activated kinase. Moreover, detailed molecular
      analysis of dsRNA-induced cell death established the proapoptotic role of IL-1R
      associated kinase-4 and NF-kappaB downstream of TLR3 as well as the activation of
      the extrinsic caspases. The direct proapoptotic activity of endogenous human TLR3
      expressed by cancerous cells reveals a novel aspect of the multiple-faced TLR
      biology, which may open new clinical prospects for using TLR3 agonists as
      cytotoxic agents in selected cancers.

PMID- 16585586
TI  - Novel immunostimulatory agent based on CpG oligodeoxynucleotide linked to the
      nontoxic B subunit of cholera toxin.
AB  - In this study, we report the development of a novel, rationally designed
      immunostimulatory adjuvant based on chemical conjugation of CpG
      oligodeoxynucleotide (ODN) to the nontoxic B subunit of cholera toxin (CTB). We
      demonstrate that the immunostimulatory effects of CpG can be dramatically
      enhanced by conjugation to CTB. Thus, CpG ODN linked to CTB (CTB-CpG) was shown
      to be a more potent stimulator of proinflammatory cytokine and chemokine
      responses in murine splenocytes and human PBMCs than those of CpG ODN alone in
      vitro. The presence of CpG motif, but not modified phosphorothioate ODN backbone,
      was found to be critical for the enhanced immunostimulatory effects of CTB-CpG.
      Our mode-of-action studies, including studies on cells from specifically gene
      knockout mice suggest that similar to CpG, CTB-CpG exerts its immunostimulatory
      effects through a TLR9/MyD88- and NF-kappaB-dependent pathway. Surprisingly, and
      as opposed to CpG ODN, CTB-CpG-induced immunity was shown to be independent of
      endosomal acidification and resistant to inhibitory ODN. Furthermore,
      preincubation of CTB-CpG with GM1 ganglioside reduced the immunostimulatory
      effects of CTB-CpG to those of CpG ODN alone. Interestingly, conjugation of CpG
      ODN to CTB confers an enhanced cross-species activity to CpG ODN. Furthermore,
      using tetanus toxoid as a vaccine Ag for s.c. immunization, CTB-CpG markedly
      enhanced the Ag-specific IgG Ab response and altered the specific pattern of Ab
      isotypes toward a Th1 type response. To our knowledge, CTB is the first nontoxic
      derivative of microbial toxins discovered that when chemically linked to CpG
      remarkably augments the CpG-mediated immune responses.

PMID- 16585587
TI  - The LFA-1 adhesion molecule is required for protective immunity during pulmonary
      Mycobacterium tuberculosis infection.
AB  - Host immunity to Mycobacterium tuberculosis is mediated by T cells that recognize
      and activate infected macrophages to control intracellular bacterial replication.
      The early appearance of T cells in the lungs of infected mice correlates with
      greater resistance to infection. However, it is unknown whether the trafficking
      of T cells to the lung following infection is dependent upon the expression of
      certain adhesion molecules. To address this question, we infected knockout (KO)
      mice that have defective expression of CD11a, CD11b, CD18, CD62, CD103, or beta7.
      We found that the integrins CD11a and CD18 are absolutely required for host
      resistance following infection with aerosolized M. tuberculosis. Although Ag
      specific T cells are generated following infection of CD11a KO mice, T cell
      priming is delayed, T cell trafficking to the lung is impaired, and fewer ESAT6
      specific CD4+ T cells are found in the lungs of CD11a KO mice compared with
      control mice. Thus, LFA-1 (CD11a/CD18) plays an essential role in immunity to M.
      tuberculosis infection.

PMID- 16585588
TI  - Targeted immunomodulation of the NF-kappaB pathway in airway epithelium impacts
      host defense against Pseudomonas aeruginosa.
AB  - We investigated the impact of inflammatory signaling in airway epithelial cells
      on host defense against Pseudomonas aeruginosa, a major cause of nosocomial
      pneumonia. In mice, airway instillation of P. aeruginosa resulted in NF-kappaB
      activation in the lungs that was primarily localized to the bronchial epithelium
      at 4 h, but was present in a variety of cell types by 24 h. We modulated NF
      kappaB activity in airway epithelium by intratracheal delivery of adenoviral
      vectors expressing RelA (AdRelA) or a dominant inhibitor of NF-kappaB before P.
      aeruginosa infection. Bacterial clearance was enhanced by up-regulation of NF
      kappaB activity following AdRelA administration and was impaired by treatment
      with a dominant inhibitor of NF-kappaB. The TNF-alpha concentration in lung
      lavage was increased by AdRelA treatment and beneficial effects of NF-kappaB up
      regulation were abrogated in TNF-alpha-deficient mice. In contrast, NF-kappaB
      inhibition reduced MIP-2 expression and neutrophil influx following P. aeruginosa
      infection. Therefore, inflammatory signaling through the NF-kappaB pathway in
      airway epithelial cells critically regulates the innate immune response to P.
      aeruginosa.

PMID- 16585589
TI  - Enhanced macrophage activity in granulomatous lesions of immune mice challenged
      with Mycobacterium tuberculosis.
AB  - In this study, we evaluated the cellular influx and cytokine environment in the
      lungs of mice made immune by prior vaccination with Mycobacterium bovis bacillus
      Calmette-Guerin compared with control mice after infection with Mycobacterium
      tuberculosis to characterize composition of protective lesions in the lungs.
      Immune mice controlled the growth of the M. tuberculosis challenge more
      efficiently than control mice. In immune animals, granulomatous lesions were
      smaller and had a more lymphocytic core, less foamy cells, less parenchymal
      inflammation, and slower progression of lung pathology than in lungs of control
      mice. During the chronic stage of the infection, the bacterial load in the lungs
      of immune mice remained at a level 10 times lower than control mice, and this was
      associated with reduced numbers of CD4P(+P) and CD8P(+P) T cells, and the lower
      expression of protective (IL-12, IFN-gamma), inflammatory (TNF-alpha),
      immunoregulatory (GM-CSF), and immunosuppressive (IL-10) cytokines. The immune
      mice had higher numbers of CD11b- CD11c(high) DEC-205(low) alveolar macrophages,
      but lower numbers of CD11b+ CD11c(high) DEC-205(high) dendritic cells, with the
      latter expressing significantly lower levels of the antiapoptotic marker TNFR
      associated factor-1. Moreover, during the early stage of chronic infection, lung
      dendritic cells from immune mice expressed higher levels of MHC class II and CD40
      molecules than similar cells from control mice. These results indicate that while
      a chronic disease state is the eventual outcome in both control and immune mice
      infected with M. tuberculosis by aerosol exposure, immune mice develop a
      protective granulomatous lesion by increasing macrophage numbers and reduced
      expression of protective and inflammatory cytokines.

PMID- 16585590
TI  - CpG oligodeoxynucleotides protect newborn mice from a lethal challenge with the
      neurotropic Tacaribe arenavirus.
AB  - The innate immune system is key to limiting the early spread of most pathogens
      and directing the development of Ag-specific immunity. Recently, a number of
      synthetic molecules that activate the innate immune system by stimulating TLRs
      have been identified. Among them, synthetic oligodeoxynucleotides (ODNs)
      containing unmethylated CpG motifs (CpG ODNs) were shown to activate TLR9-bearing
      B cells, macrophages, and dendritic cells to induce a strong proinflammatory
      milieu and a type 1-biased immune response that protects mice from a variety of
      parasitic, bacterial, and viral infections. Although the protective effect of CpG
      ODN in adult mice was well established, its effectiveness in neonates, which have
      lower numbers of dendritic, B, and T cells and tend to favor Th2 responses, was
      unclear. This study uses the New World arenavirus Tacaribe, a neurotropic
      pathogen that is lethal in newborn mice, to explore the effectiveness of TLR
      mediated innate immune responses. Neonatal BALB/c mice treated with CpG ODN at
      the time of infection had reduced viral load (p < 0.01) and increased survival
      (52%, p < 0.001 i.p.; 36%, p < 0.05 intranasally). Protection was achieved in
      mice treated no later than 3 days postchallenge and appears to be mediated by an
      increase in Ag-specific Abs (IgG and IgM) and to require inducible NO synthase
      expression and NO production. To our knowledge, this is the first study assessing
      the mechanisms by which CpG ODN can protect mice from a neurotropic viral
      infection.

PMID- 16585591
TI  - Inducible activation of TLR4 confers resistance to hyperoxia-induced pulmonary
      apoptosis.
AB  - TLRs are essential mediators of host defense against infection via recognition of
      unique microbial structures. Recent observations indicate that TLR4, the
      principal receptor for bacterial LPS, may also be activated by noninfectious
      stimuli including host-derived molecules and environmental oxidant stress. In
      mice, susceptibility to ozone-induced lung permeability has been linked to the
      wild-type allele of TLR4, whereas deficiency of TLR4 predisposes to lethal lung
      injury in hyperoxia. To precisely characterize the role of lung epithelial TLR4
      expression in the host response to oxidant stress, we have created an inducible
      transgenic mouse model that targets the human TLR4 signaling domain to the
      airways. Exposure of induced transgenic mice to hyperoxia revealed a significant
      reduction in pulmonary apoptosis compared with controls. This phenotype was
      associated with sustained up-regulation of antiapoptotic molecules such as heme
      oxygenase-1 and Bcl-2, yet only transient activation of the transcription factor
      NF-kappaB. Specific in vivo knockdown of pulmonary heme oxygenase-1 or Bcl-2
      expression by intranasal administration of short interfering RNA blocked the
      effect of TLR4 signaling on hyperoxia-induced lung apoptosis. These results
      define a novel role for lung epithelial TLR4 as a modulator of cellular apoptosis
      in response to oxidant stress.

PMID- 16585592
TI  - STAT1 in peripheral tissue differentially regulates homing of antigen-specific
      Th1 and Th2 cells.
AB  - Th1 and Th2 effector CD4+ T cells orchestrate distinct counterregulatory
      biological responses. To deliver effective tissue Th1- and Th2-type responses,
      Th1 and Th2 cell recruitment into tissue must be differentially regulated. We
      show that tissue-derived STAT1 controls the trafficking of adoptively
      transferred, Ag-specific, wild-type Th1 cells into the lung. Trafficking of Th1
      and Th2 cells is differentially regulated as STAT6, which regulates Th2 cell
      trafficking, had no effect on the trafficking of Th1 cells and STAT1 deficiency
      did not alter Th2 cell trafficking. We demonstrate that STAT1 control of Th1 cell
      trafficking is not mediated through T-bet. STAT1 controls the recruitment of Th1
      cells through the induction of CXCL9, CXCL10, CXCL11, and CXCL16, whose
      expression levels in the lung were markedly decreased in STAT1-/- mice. CXCL10
      replacement partially restored Th1 cell trafficking in STAT1-deficient mice in
      vivo, and deficiency in CXCR3, the receptor for CXCL9, CXCL10, and CXCL11,
      impaired the trafficking of adoptively transferred Th1 cells in wild-type mice.
      Our work identifies that STAT1 in peripheral tissue regulates the homing of Ag
      specific Th1 cells through the induction of a distinct subset of chemokines and
      establishes that Th1 and Th2 cell trafficking is differentially controlled in
      vivo by STAT1 and STAT6, respectively.

PMID- 16585593
TI  - Role of CCR5 in the pathogenesis of IL-13-induced inflammation and remodeling.
AB  - IL-13 is a major effector at sites of Th2 inflammation and tissue remodeling. In
      these locations, it frequently coexists with the CCR5 chemokine receptor and its
      ligands MIP-1alpha/CCL3 and MIP-1beta/CCL4. We hypothesized that CCR5 induction
      and activation play important roles in the pathogenesis of IL-13-induced tissue
      responses. To test this hypothesis, we evaluated the effects of IL-13 on the
      expression of CCR5 in the murine lung. We also compared the effects of lung
      targeted transgenic IL-13 in mice treated with anti-CCR5 or an Ab control and
      mice with wild-type or null CCR5 loci. These studies demonstrate that IL-13 is a
      potent stimulator of epithelial cell CCR5 expression. They also demonstrate that
      CCR5 neutralization or a deficiency of CCR5 significantly decreases IL-13-induced
      inflammation, alveolar remodeling, structural and inflammatory cell apoptosis,
      and respiratory failure and death. Lastly, these studies provide mechanistic
      insights by demonstrating that CCR5 is required for optimal IL-13 stimulation of
      select chemokines (MIP-1alpha/CCL3, MIP-1beta/CCL4, MCP-1/CCL-2), matrix
      metalloproteinase-9 and cell death regulators (Fas, TNF, TNFR1, TNFR2, Bid),
      optimal IL-13 inhibition of alpha1-antitrypsin, and IL-13-induction of and
      activation of caspases-3, -8, and-9. Collectively, these studies demonstrate that
      CCR5 plays a critical role in the pathogenesis of IL-13-induced inflammation and
      tissue remodeling.

PMID- 16585594
TI  - ASC directs NF-kappaB activation by regulating receptor interacting protein-2
      (RIP2) caspase-1 interactions.
AB  - Receptor interacting protein-2 (RIP2) is a caspase recruitment domain (CARD)
      containing kinase that interacts with caspase-1 and plays an important role in NF
      kappaB activation. Apoptosis-associated speck-like protein containing a CARD
      (ASC) is a PYRIN and CARD-containing molecule, important in the induction of
      apoptosis and caspase-1 activation. Although RIP2 has also been linked to caspase
      1 activation, RIP2 knockout animals fail to show a defect in caspase-1-mediated
      processing of proIL-1beta to its active form. Therefore, RIP2 function in binding
      to caspase-1 remains poorly understood. We hypothesized that caspase-1 may serve
      as a scaffolding molecule that promotes RIP2 interaction with IkappaB kinase
      gamma thus inducing NF-kappaB activation. We further hypothesized that ASC, which
      also interacts with caspase-1 via its CARD, may interfere with the caspase-1 RIP2
      interaction. In HEK293 cells, ASC induced prominent activation of caspase-1 and
      proIL-1beta processing. RIP2 transient transfection induced transcription of an
      NF-kappaB reporter gene. This RIP2-induced NF-kappaB activity and caspase-1
      binding was inhibited in a dose-dependent fashion by ASC. Consistent with a role
      for caspase-1 as a scaffold for RIP2, caspase-1 knockout macrophages were
      suppressed in their ability to activate NF-kappaB, and septic caspase-1 knockout
      animals produced less IL-6, a functional marker of NF-kappaB activity. Lastly,
      THP-1 cells treated with small interfering RNA for ASC decreased their caspase-1
      activity while enhancing their NF-kappaB signal. These data suggest that ASC may
      direct caspase-1 away from RIP2-mediated NF-kappaB activation, toward caspase-1
      mediated processing of proIL-1beta by interfering with the RIP2 caspase-1
      interaction.

PMID- 16585595
TI  - Effect of D-alanylation of (lipo)teichoic acids of Staphylococcus aureus on host
      secretory phospholipase A2 action before and after phagocytosis by human
      neutrophils.
AB  - Invading bacteria such as Staphylococcus aureus induce mobilization of
      professional phagocytes (e.g., neutrophils) and extracellular antibacterial
      proteins (e.g., group IIA phospholipase A2 (gIIA PLA2)). Accumulation of gIIA
      PLA2 in inflammatory fluids confers potent extracellular antistaphylococcal
      activity and at lower concentrations promotes bacterial phospholipid degradation
      during phagocytosis of S. aureus by human neutrophils. D-alanylation of (lipo)
      teichoic acids of S. aureus increases bacterial resistance to gIIA PLA2
      approximately 100-fold, raising the possibility that the resistance of ingested
      S. aureus to related gV and gX secretory PLA2 present in human neutrophil
      granules depends on D-alanylation mediated by the dlt operon. However, we show
      that isogenic wild-type and dltA S. aureus are equally resistant to gV/X PLA2
      during phagocytosis and when exposed to the purified enzymes. The fates of wild
      type and dltA S. aureus exposed to serum and human neutrophils differed
      significantly only when extracellular gIIA PLA2 was also present before
      phagocytosis. The extreme potency of the gIIA PLA2 toward dltA S. aureus suggests
      that even small amounts of this extracellular enzyme mobilized early in
      inflammation could contribute substantially to the overall cytotoxicity of acute
      inflammatory exudates toward S. aureus when D-alanylation of (lipo)teichoic acids
      is limiting.

PMID- 16585596
TI  - Duration and intensity of NF-kappaB activity determine the severity of endotoxin
      induced acute lung injury.
AB  - Activation of innate immunity in the lungs can lead to a self-limited
      inflammatory response or progress to severe lung injury. We investigated whether
      specific parameters of NF-kappaB pathway activation determine the outcome of
      acute lung inflammation using a novel line of transgenic reporter mice. Following
      a single i.p. injection of Escherichia coli LPS, transient NF-kappaB activation
      was identified in a variety of lung cell types, and neutrophilic inflammation
      resolved without substantial tissue injury. However, administration of LPS over
      24 h by osmotic pump (LPS pump) implanted into the peritoneum resulted in
      sustained, widespread NF-kappaB activation and neutrophilic inflammation that
      culminated in lung injury at 48 h. To determine whether intervention in the NF
      kappaB pathway could prevent progression to lung injury in the LPS pump model, we
      administered a specific IkappaB kinase inhibitor (BMS-345541) to down-regulate NF
      kappaB activation following the onset of inflammation. Treatment with BMS-345541
      beginning at 20 h after osmotic pump implantation reduced lung NF-kappaB
      activation, concentration of KC and MIP-2 in lung lavage, neutrophil influx, and
      lung edema measured at 48 h. Therefore, sustained NF-kappaB activation correlates
      with severity of lung injury, and interdiction in the NF-kappaB pathway is
      beneficial even after the onset of lung inflammation.

PMID- 16585597
TI  - In vitro activation of CD8 interphotoreceptor retinoid-binding protein-specific T
      cells requires not only antigenic stimulation but also exogenous growth factors.
AB  - In a previous study, we demonstrated that immunization with the uveitogenic
      peptide interphotoreceptor retinoid-binding protein (IRBP) 1-20 induces both CD4
      and CD8 uveitogenic T cells in the B6 mouse. In the current study, we determined
      the role of the CD8 IRBP-specific T cells in the pathogenesis of experimental
      autoimmune uveitis. We also determined the conditions that facilitated the
      activation of CD8 autoreactive T cells. Our results showed that the beta2
      microglobulin(-/-) mouse had a greatly decreased susceptibility to induction of
      experimental autoimmune uveitis by adoptive transfer of IRBP-specific T cells
      from B6 mice. We also showed that unlike CD4 autoreactive T cells, activated CD8
      autoreactive T cells produced only a limited number and amounts of growth
      factors. As a result, in the absence of exogenously supplied growth factor(s),
      CD8 T cell activation and expansion were aborted. However, the growth and
      expansion of triggered CD8 autoreactive T cells could be supported by various
      cytokines. In addition to factors produced by activated CD4 autoreactive T cells,
      factors produced by nonlymphoid cells, such as IL-7 and IL-15, and unidentified
      factors in the culture supernatants of astrocytes and retinal pigment epithelial
      cells support the CD8 autoreactive T cells as well. Finally, we showed that,
      although several cytokines augmented the CD8 T cell response in vitro, different
      cytokines appeared to act on different CD8 subsets or on different
      activation/differentiation phases of CD8 autoreactive T cells. As a result,
      cytokines, such as IL-7, supported the proliferation and survival of CD8 IRBP
      specific T cells, while others had only a growth-promoting effect.

PMID- 16585598
TI  - Histone hyperacetylation is associated with amelioration of experimental colitis
      in mice.
AB  - Inhibitors of histone deacetylases (HDAC) are being studied for their
      antiproliferative effects in preclinical cancer trials. Recent studies suggest an
      anti-inflammatory role for this class of compounds. Because inflammatory bowel
      disease is associated with an increased risk of malignancies, agents with
      antiproliferative and anti-inflammatory properties would be of therapeutic
      interest. HDAC inhibitors from various classes were selected and evaluated for
      their in vitro capacity to suppress cytokine production and to induce apoptosis
      and histone acetylation. Valproic acid (VPA) and suberyolanilide hydroxamic acid
      (SAHA) were chosen for further studies in dextran sulfate sodium- and
      trinitrobenzene sulfonic acid-induced colitis in mice. In vitro, inhibition of
      HDAC resulted in a dose-dependent suppression of cytokine synthesis and apoptosis
      induction requiring higher concentrations of HDAC inhibitors for apoptosis
      induction compared with cytokine inhibition. Oral administration of either VPA or
      SAHA reduced disease severity in dextran sulfate sodium-induced colitis. The
      macroscopic and histologic reduction of disease severity was associated with a
      marked suppression of colonic proinflammatory cytokines. In parallel to the
      beneficial effect observed, a dose-dependent increase in histone 3 acetylation at
      the site of inflammation was shown under VPA treatment. Furthermore, SAHA as well
      as VPA treatment resulted in amelioration of trinitrobenzene sulfonic acid
      induced colitis, which was associated with an increase of apoptosis of lamina
      propria lymphocytes. Inhibitors of HDAC reveal strong protective effects in
      different models of experimental colitis by inducing apoptosis and suppressing
      proinflammatory cytokines, thereby representing a promising class of compounds
      for clinical studies in human inflammatory bowel disease.

PMID- 16585599
TI  - Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype.
AB  - Tumor-associated macrophages (TAM) may have tumor-promoting activity, but it is
      not clear how their phenotype is achieved. In this study, we demonstrate that
      ovarian cancer cells switch cocultured macrophages to a phenotype similar to that
      found in ovarian tumors. Tumor cells caused dynamic changes in macrophage
      cytokine, chemokine, and matrix metalloprotease mRNA, and protein-inducing
      mediators that are found in human cancer. Macrophage mannose, mannose receptor,
      and scavenger receptors (SR-As) were also up-regulated by coculture, but not by
      conditioned medium. To further validate the model, we studied SR-A regulation on
      TAM in vitro and in vivo. Coculture of murine macrophages from mice deficient in
      TNF-alpha or its receptors revealed that TNF-alpha was key to SR-A induction via
      its p75 receptor. SR-A expression was also reduced in TAM from ovarian cancers
      treated with anti-TNF-alpha Abs or grown in TNF-alpha(-/-) mice. Chemical
      communication between tumor cells and macrophages may be important in regulating
      the cancer cytokine microenvironment.

PMID- 16585600
TI  - IFN-gamma primes RAW264 macrophages and human monocytes for enhanced oxidant
      production in response to CpG DNA via metabolic signaling: roles of TLR9 and
      myeloperoxidase trafficking.
AB  - Macrophages and monocytes are activated by CpG DNA motifs to produce NO, which is
      enhanced dramatically by IFN-gamma. We hypothesize that synergistic cellular
      responses to IFN-gamma and CpG DNA are due to cross-talk between metabolic
      signaling pathways of leukocytes. Adherent RAW264.7 macrophages and human
      monocytes exhibited NAD(P)H autofluorescence oscillation periods of approximately
      20 s. IFN-gamma increased the oscillatory amplitude, which was required for CpG
      DNA-mediated metabolic changes. These alterations in metabolic dynamics required
      the appropriate combinations of murine/human TLR9 and murine/human-specific CpG
      DNA. Other factors that also promoted an increase in metabolic oscillatory
      amplitude could substitute for IFN-gamma. Because recent studies have shown that
      the metabolic frequency is coupled to the hexose monophosphate shunt, and the
      amplitude is coupled to the peroxidase cycle, we tested the hypothesis that
      myeloperoxidase (MPO) participates in IFN-gamma priming for oxidant production.
      MPO inhibitors blocked cell responses to IFN-gamma and CpG DNA. In the absence of
      IFN-gamma exposure, the effects of CpG DNA could be duplicated by MPO addition to
      cell samples. Moreover, monocytes from MPO knockout mice were metabolically
      unresponsive to IFN-gamma and CpG DNA. NAD(P)H frequency doubling responses due
      to CpG DNA were blocked by an inhibitor of the hexose monophosphate shunt.
      Because NAD(P)H participates in electron trafficking to NO and superoxide anions,
      we tested oxidant production. Although CpG DNA alone had no effect, IFN-gamma
      plus CpG enhanced NO and reactive oxygen metabolite release compared with IFN
      gamma treatment alone. We suggest that amplitude and frequency modulation of
      cellular metabolic oscillations contribute to intracellular signaling synergy.

PMID- 16585601
TI  - Contrasting roles for domain 4 of VCAM-1 in the regulation of cell adhesion and
      soluble VCAM-1 binding to integrin alpha4beta1.
AB  - Cell adhesion mediated by the interaction between integrin alpha4beta1 and VCAM-1
      is important in normal physiologic processes and in inflammatory and autoimmune
      disease. Numerous studies have mapped the alpha4beta1 binding sites in VCAM-1
      that mediate cell adhesion; however, little is known about the regions in VCAM-1
      important for regulating soluble binding. In the present study, we demonstrate
      that 6D VCAM-1 (an alternatively spliced isoform of VCAM-1 lacking Ig-like domain
      4) binds alpha4beta1 with a higher relative affinity than does the full-length
      form of VCAM-1 containing 7 Ig-like extracellular domains (7D VCAM-1). In
      indirect binding assays, the EC50 of soluble 6D VCAM-1 binding to alpha4beta1 on
      Jurkat cells (in 1 mM MnCl2) was 2 x 10(-9) M, compared with 7D VCAM-1 at 11 x
      10(-9) M. When used in solution to inhibit alpha4beta1 mediated cell adhesion,
      the IC50 of 6D VCAM-1 was 13 x 10(-9) M, compared with 7D VCAM-1 measured at 150
      x 10(-9) M. Removal of Ig-like domains 4, 5, or 6, or simply substituting Asp328
      in domain 4 of 7D VCAM-1 with alanine, caused increased binding of soluble 7D
      VCAM-1 to alpha4beta1. In contrast, cells adhered more avidly to 7D VCAM-1 under
      shear force, as it induced cell spreading at lower concentrations than did 6D
      VCAM-1. Finally, soluble 6D VCAM-1 acts as an agonist through alpha4beta1 by
      augmenting cell migration and inducing cell aggregation. These results indicate
      that the domain 4 of VCAM-1 plays a contrasting role when VCAM-1 is presented in
      solution or as a cell surface-expressed adhesive substrate.

PMID- 16585602
TI  - Substance P stimulates cyclooxygenase-2 and prostaglandin E2 expression through
      JAK-STAT activation in human colonic epithelial cells.
AB  - Substance P (SP) via its neurokinin-1 receptor (NK-1R) regulates several
      gastrointestinal functions. We previously reported that NK-1R-mediated chloride
      secretion in the colon involves formation of PG. PGE2 biosynthesis is controlled
      by cyclooxygenase-1 (COX-1) and COX-2, whose induction involves the STATs. In
      this study, we examined whether SP stimulates PGE2 production and COX-2
      expression in human nontransformed NCM460 colonocytes stably transfected with the
      human NK-1R (NCM460-NK-1R cells) and identified the pathways involved in this
      response. SP exposure time and dose dependently induced an early (1-min)
      phosphorylation of JAK2, STAT3, and STAT5, followed by COX-2 expression and PGE2
      production by 2 h. Pharmacologic experiments showed that PGE2 production is
      dependent on newly synthesized COX-2, but COX-1 protein. Inhibition of protein
      kinase Ctheta (PKCtheta), but not PKCepsilon and PKCdelta, significantly reduced
      SP-induced COX-2 up-regulation, and JAK2, STAT3, and STAT5 phosphorylation.
      Pharmacological blockade of JAK inhibited SP-induced JAK2, STAT3, and STAT5
      phosphorylation; COX-2 expression; and PGE2 production. Transient transfection
      with JAK2 short-interferring RNA reduced COX-2 promoter activity and JAK2
      phosphorylation, while RNA interference of STAT isoforms showed that STAT5
      predominantly mediates SP-induced COX-2 promoter activity. Site-directed mutation
      of STAT binding sites on the COX-2 promoter completely abolished COX-2 promoter
      activity. Lastly, COX-2 expression was elevated in colon of mice during
      experimental colitis, and this effect was normalized by administration of the NK
      1R antagonist CJ-12,255. Our results demonstrate that SP stimulates COX-2
      expression and PGE2 production in human colonocytes via activation of the JAK2
      STAT3/5 pathway.

PMID- 16585603
TI  - A severe form of human combined immunodeficiency due to mutations in DNA ligase
      IV.
AB  - DNA ligase IV (LigIV) deficiency was identified as the molecular basis for a
      severe form of combined immunodeficiency in two microcephalic siblings with
      cellular radiosensitivity. In one patient the diagnosis was made directly after
      birth, allowing analysis of the role of LigIV in the development of specific
      immune cells. Absolute numbers of B cells were reduced 100-fold and alphabeta T
      cells 10-fold, whereas gammadelta T cells were normal. Spectratyping of all three
      cell populations showed a diverse repertoire, but sequencing of IgH V(D)J
      junctions revealed shorter CDR3 regions due to more extensive nucleotide
      deletions among D and J elements and fewer N nucleotide insertions. Clonal
      restriction of IgG-expressing, but not IgM-expressing, B cells and the lack of
      primary and secondary lymph node follicles indicated impaired class switch
      recombination. Observations in the older sibling showed that this rudimentary
      immune system was able to mount specific responses to infection. However, partial
      Ab responses and extensive amplification of gammadelta T cells could not prevent
      a life-threatening course of viral and bacterial infections, the development of
      an EBV-induced lymphoma, and immune dysregulation reflected by severe autoimmune
      cytopenia. Impaired generation of immune diversity under conditions of limited
      LigIV activity can cause a human SCID variant with a characteristic immunological
      phenotype.

PMID- 16585605
TI  - Human complete Stat-1 deficiency is associated with defective type I and II IFN
      responses in vitro but immunity to some low virulence viruses in vivo.
AB  - The autosomal recessive form of human complete Stat-1 deficiency is a rare
      disorder, thus far reported in two unrelated patients, both of whom developed
      disseminated bacillus Calmette-Guerin (BCG) and subsequently died of viral
      illnesses before detailed studies of the condition could be performed. It is
      associated with impaired cellular responses to both IFN-gamma and IFN-alphabeta
      via Stat-1-containing complexes. We describe a third patient with complete Stat-1
      deficiency and disseminated BCG infection, who died 3 mo after bone marrow
      transplantation. The patient's EBV-transformed B cells did not express Stat-1
      protein and did not activate Stat-1-containing transcription factors. We also
      report the ex vivo responses of a Stat-1-deficient patient's fresh blood cells to
      IFN-gamma and the in vitro responses of a SV40-transformed fibroblastic cell line
      to IFN-gamma and IFN-alphabeta. There was no response to IFN-gamma in terms of IL
      12 production and HLA class II induction, accounting for vulnerability to BCG.
      Moreover, IFN-alphabeta did not suppress HSV and vesicular stomatitis virus
      replication in fibroblasts, although in vivo the patient was able to successfully
      clear at least some viruses. This study broadens our understanding of complete
      Stat-1 deficiency, a severe form of innate immunodeficiency. Stat-1 deficiency
      should be suspected in children with severe infections, notably but not
      exclusively patients with mycobacterial or viral diseases.

PMID- 16585604
TI  - Allergen-specific MHC class II tetramer+ cells are detectable in allergic, but
      not in nonallergic, individuals.
AB  - Allergen-specific cells are present in very low frequency in peripheral blood of
      humans, and differ in function in allergic and nonallergic individuals. We report
      in this study that soluble class II MHC tetramers can be used to directly
      identify and study such allergen epitope-specific CD4+ T cells in humans. We
      identified the major antigenic epitope of rye grass allergen Lol p 1 in HLA
      DRB1*0401 individuals using HLA-DR*0401 transgenic mice and peripheral blood
      cells from HLA-DR*0401 individuals. Using DRB1*0401 tetramers loaded with this
      major epitope of Lol p 1, we detected allergen-specific CD4+ T cells in the
      peripheral blood of DRB1*0401 rye grass allergic individuals after ex vivo
      expansion with allergen. These tetramer-positive cells produced IL-4, but little
      IFN-gamma. In contrast, we were unable to detect rye grass tetramer-positive
      cells in cultures from HLA-DR*0401 nonallergic individuals, even after expansion
      with IL-2. Thus, our results suggest that rye grass allergen-specific T cells in
      DR*0401 nonallergic subjects are present at very low levels (e.g., because of
      deletion or suppression), differ in a fundamental way in their requirement for ex
      vivo expansion (e.g., they may be anergic), or use TCRs distinct from those of
      allergic individuals. Thus, analysis using DRB1*0401 tetramers loaded with a
      major epitope of Lol p 1 indicates that allergen-specific CD4+ T cells in
      nonallergic individuals are distinct from those in allergic subjects.

PMID- 16585606
TI  - Monoclonal pathogenic antibodies to the thyroid-stimulating hormone receptor in
      Graves' disease with potent thyroid-stimulating activity but differential
      blocking activity activate multiple signaling pathways.
AB  - The thyroid target Ag for disease-inducing autoantibodies in Graves' disease is
      the receptor for thyroid-stimulating hormone (TSH), but little is known about the
      molecular basis of this pathogenic Ab response. We describe the characteristics
      of two high- affinity mAbs developed from an experimental murine model of
      hyperthyroid Graves' disease that exhibit potent thyroid-stimulating activity.
      Nanogram concentrations of the IgG mAbs KSAb1 and KSAb2 and their Fab induce full
      stimulation of the TSH receptor that is matched by the ligand TSH and, thus, act
      as full agonists for the receptor. However, KSAb1 and KSAb2 display differential
      activities in their ability to block TSH-mediated stimulation of the receptor,
      indicating subtle differences in their biological properties. In displacement
      studies, IgG and Fabs of KSAb1 and KSAb2 compete with Graves' disease
      autoantibodies as well as thyroid-blocking Abs present in some hypothyroid
      patients, indicating a close relationship between these autoimmune determinants
      on the receptor. In passive transfer studies, single injections of microgram
      quantities of KSAb1 or KSAb2 IgG led to rapid elevation of serum thyroxine and a
      hyperthyroid state that was maintained for a number of days. The thyroid glands
      showed evidence of cell necrosis, but there was no accompanying mononuclear cell
      infiltrate. In studying their receptor activation pathways, both KSAb1 and KSAb2
      provoked phosphorylation of the intracellular ERK1/2 pathway in primary
      thyrocytes, indicating that multiple signaling pathways may participate in the
      pathogenesis of Graves' disease. In summary, our findings emphasize the
      similarities of the experimental mouse model in reproducing the human disorder
      and provide improved means for characterizing the molecular basis of this
      pathogenic response.

PMID- 16585607
TI  - Identification of novel subdominant epitopes on the carcinoembryonic antigen
      recognized by CD4+ T cells of lung cancer patients.
AB  - The carcinoembryonic Ag (CEA) is an attractive target for immunotherapy because
      of its expression profile and role in tumor progression. To verify the existence
      of spontaneous anti-CEA CD4+ T cells in lung cancer patients, we first identified
      CEA sequences forming naturally processed epitopes, and then used the identified
      epitopes to test their recognition by CD4+ T cells from the patients. We had
      previously identified CEA(177-189/355-367) as an immunodominant epitope
      recognized by CD4+ T cells in association with several HLA-DR alleles. In this
      study, we identified four additional subdominant CEA sequences (CEA(99-111),
      CEA(425-437), CEA(568-582), and CEA(666-678)), recognized in association with one
      or more HLA-DR alleles. Peptide-specific CD4+ T cells produced proinflammatory
      cytokines when challenged with the native protein and CEA-expressing tumor cells,
      thus demonstrating that the identified CEA sequences contain naturally processed
      epitopes. However, CEA is expressed in the thymus and belongs to the CD66 family
      that comprises highly homologous molecules expressed on hemopoietic cells,
      raising concerns about tolerance interfering with the in vivo development of anti
      CEA immunity. We thus tested the spontaneous reactivity to the identified
      epitopes of peripheral blood CD4+ T lymphocytes from eight early-stage lung
      cancer patients bearing CEA-positive tumors. We found GM-CSF- and IFN-gamma
      producing CD4+ T cells in two patients. Our data indicate that CD4+ immune
      responses against CEA develop in neoplastic patients, suggesting that tolerance
      toward CEA or cross-reactive CD66 homologous molecules might be either not
      absolute or be overcome in the neoplastic disease.

PMID- 16585608
TI  - CDR3 spectratyping analysis of the TCR repertoire in myasthenia gravis.
AB  - Because myasthenia gravis (MG) is an autoimmune disease mediated by Abs specific
      for the acetylcholine receptor, helper T cells play a role in Ab production. In
      this study, we have performed large-scale cross-sectional and longitudinal TCR
      studies by CDR3 spectratyping using PBL and thymus tissues from MG patients. We
      found that there was no preferential usage of any particular TCR beta-chains that
      was identical among MG patients. However, the longitudinal study clearly
      demonstrated that one or more TCR Vbeta expansions persisted frequently in MG
      patients. Importantly, persistent TCR expansions correlated with clinical
      severity and high anti-acetylcholine receptor Ab titer. Finally, examinations of
      T cells expressing CXCR5, i.e., follicular B-helper T cells, revealed that
      spectratype expansions in MG patients were detected mainly in the CD4+ CXCR5+ T
      cell populations, whereas CD8+ T cells were the major source of clonal expansion
      in healthy subjects. These findings suggest that persistent clonal expansions of
      T cells in MG patients are associated with the development and maintenance of MG.
      Close examination of pathogenic T cells in MG provides useful information to
      elucidate the pathogenesis and to estimate the disease status.

PMID- 16585610
TI  - Determination of steroidal estrogens in flushed dairy manure wastewater by gas
      chromatography-mass spectrometry.
AB  - There is a critical need to accurately measure the concentrations of natural
      steroidal estrogens in flushed dairy manure wastewater (FDMW) to assess any
      potential risk of waterway contamination resulting from land application.
      Estrogens are a concern because low concentrations (10-100 ng L-1) in water can
      adversely affect aquatic vertebrate species such as fish, turtles, and frogs by
      disrupting the normal function of their endocrine systems. The objective of this
      study was to develop a sample preparation method that permits the quantification
      of four natural steroidal estrogens (17alpha-estradiol, 17beta-estradiol,
      estrone, and estriol) in FDMW by gas chromatography-mass spectrometry (GC-MS).
      Solid-phase extraction with graphitized carbon black was used for the bulk
      extraction of estrogens from FDMW and additional sample purification was
      accomplished with C-18. The sample preparation method allowed estrogens to be
      detected accurately by GC-MS in FDMW. Spiked recovery experiments indicated that
      the method is satisfactory for measuring the estrogens of interest in FDMW with
      average recovery of >90%. As expected in FDMW, characterization of the estrogen
      profile revealed a large abundance of 17alpha-estradiol relative to 17beta
      estradiol and estrone. Estriol was not detected in FDMW. The methodology
      developed in this research helps provide an analytical foundation for the
      quantification of steroidal estrogens in FDMW by GC-MS.

PMID- 16585609
TI  - BCR/ABL oncogene directly controls MHC class I chain-related molecule A
      expression in chronic myelogenous leukemia.
AB  - MHC class I chain-related molecules (MIC) participate in immune surveillance of
      cancer through engagement of the NKG2D-activating receptor on NK and T cells.
      Decreased NKG2D expression and function upon chronic exposure to NKG2D ligands
      and/or soluble forms of MIC (sMIC) may participate in immune escape. In chronic
      myeloid leukemia, a malignancy caused by the BCR/ABL fusion oncoprotein, we
      showed cell surface expression of MICA on leukemic, but not healthy, donor
      hemopoietic CD34+ cells. At diagnosis, chronic myeloid leukemia patients had
      abnormally high serum levels of sMICA and weak NKG2D expression on NK and CD8+ T
      cells, which were restored by imatinib mesylate (IM) therapy. In the BCR/ABL+
      cell line K562, IM decreased both surface MICA/B expression and NKG2D-mediated
      lysis by NK cells. Silencing BCR/ABL gene expression directly evidenced its role
      in the control of MICA expression. IM did not affect MICA mRNA levels, but
      decreased MICA protein production and release. Sucrose density gradient
      fractionation of K562 cytoplasmic extracts treated with IM showed a shift in the
      distribution of MICA mRNA from the polysomal toward the monosomal fractions,
      consistent with decreased translation. Among the major pathways activated by
      BCR/ABL that regulate translation, PI3K and mammalian target of rapamycin were
      shown to control MICA expression. These data provide evidence for direct control
      of MICA expression by an oncogene in human malignancy and indicate that
      posttranscriptional mechanisms may participate in the regulation of MICA
      expression.

PMID- 16585611
TI  - Mineralization of hormones in breeder and broiler litters at different water
      potentials and temperatures.
AB  - When poultry litter is landspread, steroidal hormones present in the litter may
      reach surface waters, where they may have undesirable biological effects. In a
      laboratory study, we determined the mineralization of [4-14C]-labeled 17beta
      estradiol, estrone, and testosterone in breeder litter at three different water
      potentials (-56, -24, and -12 MPa) and temperatures (25, 35, and 45 degrees C),
      and in broiler litter at two different water potentials (-24 and -12 MPa) and
      temperatures (25 and 35 degrees C). Mineralization was similar in both litters
      and generally increased with increasing water content and decreasing temperature.
      After 23 wk at -24 MPa, an average of 27, 11, and <2% of the radiolabeled
      testosterone applied to breeder litter was mineralized to 14CO2 at 25, 35, and 45
      degrees C, respectively. In contrast, mineralization of the radiolabeled
      estradiol and estrone was <2% after 25 wk at all water potentials, except after
      17 wk at 25 degrees C and -12 MPa, where up to 5.9% of the estradiol and 7.8% of
      the estrone was mineralized. The minimal mineralization suggests that the litters
      may still be potential sources of hormones to surface and subsurface waters.

PMID- 16585612
TI  - Modeling methyl isothiocyanate soil flux and emission ratio from a field
      following a chemigation of metam-sodium.
AB  - Metam-sodium had become the most heavily used soil fumigant in recent years as
      the deadline approached for methyl bromide to phase out in January 2005. After
      application, metam-sodium decomposes rapidly to methyl isothiocyanate (MITC), a
      highly toxic compound capable of killing a wide spectrum of soil-borne pests.
      Inhalation risk of MITC ranked high among airborne agricultural pesticides in
      California. Information about off-gassing intensity and percentage of emission is
      essential for exposure risk assessment and mitigation measures, but is limited,
      especially for new application methods such as drip chemigation. Air
      concentrations of MITC were monitored around a field treated with metam-sodium
      through surface drip irrigation system. The field was tarped with plastic films
      before the chemigation. The air concentrations at receptor locations were
      simulated for the period of air monitoring with the Industrial Source Complex
      (ISC3) Dispersion Model, and soil flux density of MITC at various periods after
      chemigation was estimated through a back-calculation procedure. The estimated
      soil flux density of MITC showed a diurnal pattern, with the daytime flux
      stronger than nighttime. However, the average air concentration at nighttime was
      higher than that at daytime. Soil flux density peaked at 4.30 microg m-2 s-1 in
      the first 12-h period after chemigation, then declined with time. The MITC
      emission percentage in the first 60-h was 2.65% of applied mass, of which 57%
      occurred in the first 24-h after chemigation. The study indicated that the tarped
      bed drip application method of metam-sodium had a relatively good control of MITC
      emission from soil.

PMID- 16585613
TI  - Tillage and field scale controls on greenhouse gas emissions.
AB  - There is a lack of understanding of how associations among soil properties and
      management-induced changes control the variability of greenhouse gas (GHG)
      emissions from soil. We performed a laboratory investigation to quantify
      relationships between GHG emissions and soil indicators in an irrigated
      agricultural field under standard tillage (ST) and a field recently converted (2
      yr) to no-tillage (NT). Soil cores (15-cm depth) were incubated at 25 degrees C
      at field moisture content and 75% water holding capacity. Principal component
      analysis (PCA) identified that most of the variation of the measured soil
      properties was related to differences in soil C and N and soil water conditions
      under ST, but soil texture and bulk density under NT. This trend became more
      apparent after irrigation. However, principal component regression (PCR)
      suggested that soil physical properties or total C and N were less important in
      controlling GHG emissions across tillage systems. The CO2 flux was more strongly
      determined by microbial biomass under ST and inorganic N content under NT than
      soil physical properties. Similarly, N2O and CH4 fluxes were predominantly
      controlled by NO3- content and labile C and N availability in both ST and NT
      soils at field moisture content, and NH4+ content after irrigation. Our study
      indicates that the field-scale variability of GHG emissions is controlled
      primarily by biochemical parameters rather than physical parameters. Differences
      in the availability and type of C and N sources for microbial activity as
      affected by tillage and irrigation develop different levels and combinations of
      field-scale controls on GHG emissions.

PMID- 16585615
TI  - Soil microbial and faunal community responses to bt maize and insecticide in two
      soils.
AB  - The effects of maize (Zea mays L.), genetically modified to express the Cry1Ab
      protein (Bt), and an insecticide on soil microbial and faunal communities were
      assessed in a glasshouse experiment. Soil for the experiment was taken from field
      sites where the same maize cultivars were grown to allow comparison between
      results under glasshouse conditions with those from field trials. Plants were
      grown in contrasting sandy loam and clay loam soils, half were sprayed with a
      pyrethroid insecticide (deltamethrin) and soil samples taken at the five-leaf
      stage, flowering, and maturity. The main effect on all measured parameters was
      that of soil type and there were no effects of Bt trait or insecticide on plant
      growth. The Bt trait resulted in more soil nematodes and protozoa (amoebae),
      whereas insecticide application increased plant Bt concentration and altered
      nematode community structure. The only significant effects on soil microbial
      community structure, microarthropods, and larvae of a nontarget root-feeding
      Dipteran, were due to soil type and plant growth stage. The results indicate
      that, although there were statistically significant effects of the Bt trait on
      soil populations, they were small. The relative magnitude of the effect could
      best be judged by comparison with the insecticide treatment, which was
      representative of current best practice. The Bt trait had no greater effect than
      the insecticide treatment. Results from this glasshouse experiment were in broad
      agreement with conclusions from field experiments using the same plant material
      grown in the same soils.

PMID- 16585614
TI  - Constitutive expression of a high-affinity sulfate transporter in Indian mustard
      affects metal tolerance and accumulation.
AB  - The Stylosanthes hamata SHST1 gene encodes a high-affinity sulfate transporter
      located in the plasma membrane. In this study the S. hamata SHST1 gene was
      constitutively expressed in Indian mustard [Brassica juncea (L.) Czern.] to
      investigate its importance for tolerance and accumulation of various oxyanions
      that may be transported by SHST1 and for cadmium, which is detoxified by sulfur
      rich compounds. The transgenic SHST1 lines SHST1-12C and SHST1-4C were compared
      with wild-type Indian mustard for tolerance and accumulation of arsenate,
      chromate, tungstate, vanadate, and cadmium. As seedlings the SHST1 plants
      accumulated significantly more Cd and W, and somewhat more Cr and V. The SHST1
      seedlings were less tolerant to Cd, Mo, and V compared to wild-type plants.
      Mature SHST1 plants were less tolerant than wild-type plants to Cd and Cr. SHST1
      plants accumulated significantly more Cd, Cr, and W in their roots than wild-type
      plants. In their shoots they accumulated significantly more Cr and somewhat more
      V and W. Shoot Cd accumulation was significantly lower than in wild-type, and As
      levels were somewhat reduced. Compared to wild-type plants, sulfur accumulation
      was enhanced in roots of SHST1 plants but not in shoots. Together these results
      suggest that SHST1 can facilitate uptake of other oxyanions in addition to
      sulfate and that SHST1 mediates uptake in roots rather than root-to-shoot
      translocation. Since SHST1 overexpression led to enhanced accumulation of Cr, Cd,
      V, and W, this approach shows some potential for phytoremediation, especially if
      it could be combined with the expression of a gene that confers enhanced metal
      translocation or tolerance.

PMID- 16585616
TI  - Behavior of an aerated submerged fixed-film reactor (ASFFR) under simultaneous
      organic and ammonium loading.
AB  - The performance of an aerated submerged fixed-film reactor (ASFFR) under
      simultaneous organic and ammonium loading and its effect on nitrification was
      studied. Organic loadings varied in the range of 1.93 to 5.29 g chemical oxygen
      demand (COD) m-2 d-1 and NH4-N loadings were in the range of 116 to 318 mg NH4-N
      m-2 d-1. Increments of loading rates were obtained both by increasing the flow
      rate and increasing the influent substrate in individual pilot runs. Results
      showed that with organic loading rates up to 3.97 g COD m-2 d-1, complete
      nitrification was achievable. Although high organic loading such as 5.29 g COD m
      2 d-1 could cause nitrification to stop, shifting to lower organic loadings made
      nitrification start and set rapidly to its previous steady-state concentrations.
      Comparison of results showed that in the ASFFR, nitrification would be severely
      affected by an organic loading rate of 5.29 g COD m-2 d-1 by increasing either
      the flow or the influent substrate. It should be noted that the average value of
      dissolved oxygen was 3.4 mg L-1 with an air supply of 15 L min-1, and there was
      no indication of oxygen limitation. The results of this study show the
      flexibility of ASFFRs under changing organic loads. Furthermore, for achieving
      complete nitrification and optimum application of these reactors for protecting
      receiving water from the environmental hazards of ammonium, the maximum organic
      loading that would present complete nitrification should be considered.

PMID- 16585617
TI  - Transport of giardia and manure suspensions in saturated porous media.
AB  - Experiments were conducted to elucidate the transport behavior of cysts of
      Giardia and manure suspensions through several aquifer sands. Decreasing the
      median grain size of the sand resulted in lower peak effluent concentrations and
      increased deposition of the Giardia and manure particles in the sand near the
      column inlet. The effluent concentration curves for the manure suspensions also
      exhibited asymmetric shapes that tended to include larger particle sizes as the
      manure suspension was continuously added. Simulations of the transport of Giardia
      and manure particles using a simple and flexible power law model for the solid
      water mass exchange term provided a satisfactory description of the effluent and
      spatial distribution data. The cumulative size distribution (CSD) of manure
      particles in the suspension initially and after passage through the packed
      columns was used to identify the mechanisms that were controlling the deposition
      of manure particles and Giardia. The CSD data indicated that manure particles
      were completely removed at early times by mechanical filtration and/or straining
      when the ratio of the particle to the median grain diameter was greater than
      0.003 to 0.017. However, the CSD changed with increasing time due to deposition
      induced filling of straining sites. The Giardia transport was controlled by
      straining. For a given sand, higher effluent concentrations of Giardia were
      observed in the presence than in the absence of manure suspension. The relative
      increase of Giardia in the effluent concentrations varied from 75 to 172%. Hence,
      pathogen transport studies conducted in the absence of manure suspension may
      underestimate transport potential in manure-contaminated environments.

PMID- 16585619
TI  - Environmental impact of irrigation in la violada district (Spain): I. Salt export
      patterns.
AB  - Salt loading in irrigation return flows contributes to the salinization of the
      receiving water bodies, particularly when originated in salt-affected areas as
      frequently found in the middle Ebro River basin (Spain). We determined the salt
      loading in La Violada Gully from the total dissolved solids (TDS) and flows (Q)
      during the 1995 to 1998 hydrological years. Since this gully collects flows from
      various sources, an end-member mixing analysis (EMMA) was performed to quantify
      the drainage flow from La Violada Irrigation District (VID). Three flow
      components were identified in La Violada Gully: drainage waters from VID (Qd);
      tail-waters from irrigation ditches, spill-over, and seepage from the Monegros
      Canal (Qo); and ground water inflows (Qg) originating in the dryland watershed.
      Gypsum in the soils of VID was the main source for salts in La Violada Gully
      (flow-weighted mean TDS=1720 mg L-1, dominated by sulfate and calcium). The
      contribution of Qg to the total gully flow during the 1996 irrigation season was
      low (6.5% of the total flow). The 1995 to 1998 annual salt load average in La
      Violada Gully was 78 628 Mg, 71% of which was exported during the irrigation
      season. The 1995 to 1998 irrigation season salt load average in Qd was 43 015 Mg
      (77% of the total load). Thus, irrigated agriculture in VID was the main source
      of salt loading in this gully, with a yield of 11.1 Mg of salts per hectare of
      irrigated land for the irrigation season. Efficient irrigation systems and
      irrigation management practices that reduce Qd are key factors for controlling
      off-site salt pollution of these gypsum-rich irrigated areas.

PMID- 16585618
TI  - Lead transport into Bayou Trepagnier wetlands in Louisiana, USA.
AB  - Establishment of a petroleum refinery in 1916 near the headwaters of Bayou
      Trepagnier with subsequent dredging of the bayou resulted in spoil banks
      containing high levels of Pb. A large swamp abuts the eastern bank of the bayou.
      Cores were taken from 15 baldcypress [Taxodium distichum (L.) Richard] trees
      growing in the swamp along a 610-m transect (nine trees) and a 183-m transect
      (six trees) running perpendicular from the spoil bank. The cores were crossdated,
      annual rings were measured, and 5-yr segments of the cores were prepared and
      analyzed for heavy metals. Soil samples were collected along one transect and
      analyzed for metals. Levels of Pb in Bayou Trepagnier swamp trees were compared
      to levels in nine baldcypress trees growing along Stinking Bayou, a reference
      area. During the last 100 yr, Pb in growth rings of swamp baldcypress trees
      averaged 8.6 mg/kg (SD 4.88) along one transect and 7.9 mg/kg (SD 5.39) along the
      other. Lead in the soil along the first transect dropped from >2700 mg/kg (spoil
      bank) to 10 mg/kg at 420 m into the swamp. Baldcypress trees growing near the
      refinery on the spoil bank along Bayou Trepagnier (covered in an earlier study)
      averaged 4.5 mg/kg Pb, and trees along Stinking Bayou averaged 2.1 mg/kg. Trees
      in the swamp soil with 10 to 425 mg/kg Pb concentrated much more Pb than trees
      growing on the heavily polluted bank. Greater uptake of Pb by trees in the swamp
      is discussed in terms of soil dynamics and Pb sources.

PMID- 16585620
TI  - Environmental impact of irrigation in La Violada District (Spain): II. Nitrogen
      fertilization and nitrate export patterns in drainage water.
AB  - Fertilizer leaching affects farm profitability and contributes to nonpoint-source
      pollution of receiving waters. This work aimed to establish nitrate nitrogen
      export from La Violada Gully in relation to nitrogen fertilization practices in
      its basin (La Violada Gully watershed, VGW, 19,637 ha) and especially in La
      Violada Irrigation District (VID, 5282 ha). Nitrogen (N) fertilization in VID
      (and VGW) was determined through interviews with local farmers for the hydrologic
      years 1995 and 1996 and NO3-N load in the gully was monitored from 1995 to 1998.
      The N fertilizer applied in VGW was 2175 Mg in 1995 and 2795 Mg in 1996. About
      43% was applied in VID (945 Mg in 1995 and 1161 Mg in 1996). The most fertilized
      crop was corn: 398 kg N ha-1 (665 Mg) in 1995 and 453 kg N ha-1 (911 Mg) in 1996.
      Nitrogen fertilization was higher than N uptake for irrigated crops, especially
      for corn and rice. Nitrate N load in La Violada Gully averaged 427.4 Mg yr-1.
      Seventy-five percent of the exports took place during the irrigation season
      (321.8 Mg). During the non-irrigation season maximum NO3-N loads (3.1 Mg NO3-N d
      1) were found after heavy rains following the N side-dressing of wheat in the
      rain-fed area of VGW (February). During the irrigation season NO3-N load was
      determined by outflow from the district (caused by irrigation) and to a lesser
      extent by changes in NO3 concentration (caused by fertilization), showing peaks
      in April (pre-sowing corn N fertilization and first irrigations) and June to
      August (highest irrigation months and corn side-dress N applications, maximum 6.3
      Mg NO3-N d-1 in July). Adjusting N fertilization to crops' needs, improving
      irrigation efficiencies, and better scheduling N fertilization and irrigation in
      corn could reduce N export from VID.

PMID- 16585622
TI  - Significant Escherichia coli attenuation by vegetative buffers on annual
      grasslands.
AB  - A study was conducted to estimate the retention efficiency of vegetative buffers
      for Escherichia coli deposited on grasslands in cattle fecal deposits and subject
      to natural rainfall-runoff conditions. The study was conducted on annual
      grasslands in California's northern Sierra Nevada foothills, a region with a
      distinct wet-dry season Mediterranean climate. We used 48, 2.0- by 3.0-m runoff
      plots to examine the efficacy of 0.1-, 1.1-, and 2.1-m buffers at three land
      slopes (5, 20, and 35%) and four dry vegetation matter levels (225, 560, 900, and
      4500 kg/ha) across 27 rainfall-runoff events during two rainfall seasons. Buffer
      width treatments were implemented by placement of cattle fecal material
      containing known loads of E. coli 0.1, 1.1, or 2.1 m upslope of the plot runoff
      collector. Mean total runoff to total rainfall ratio per plot ranged from 0.014:1
      to 0.019:1 and reflected the high infiltration capacity of these soils.
      Approximately 94.8 to 99.995% of total E. coli load applied to each plot appears
      to be either retained in the fecal pat and/or attenuated within 0.1 m downslope
      of the fecal pat, irrespective of the presence of a wider vegetated buffer.
      Relative to a 0.1-m buffer, we found 0.3 to 3.1 log10 reduction in E. coli
      discharge per additional meter of vegetative buffer across the range of residual
      dry vegetation matter levels, land slope, and rainfall and runoff conditions
      experienced during this project. Buffer efficiency was significantly reduced as
      runoff increased. These results support the assertion that grassland buffers are
      an effective method for reducing animal agricultural inputs of waterborne E. coli
      into surface waters.

PMID- 16585621
TI  - Sediment and phosphorus transport in irrigation furrows.
AB  - Sediment and phosphorus (P) in agricultural runoff can impair water quality in
      streams, lakes, and rivers. We studied the factors affecting P transfer and
      transport in irrigated furrows in six freshly tilled fallow fields, 110 to 180 m
      long with 0.007 to 0.012 m m-1 slopes without the interference of raindrops or
      sheet flow that occur during natural or simulated rain. The soil on all fields
      was Portneuf silt loam (coarse-silty, mixed, superactive, mesic Durinodic Xeric
      Haplocalcids). Flow rate, sediment concentration, and P concentrations were
      monitored at four, equally spaced locations in each furrow. Flow rate decreased
      with distance down the furrow as water infiltrated. Sediment concentration varied
      with distance and time with no set pattern. Total P concentrations related
      directly to sediment concentrations (r2=0.75) because typically >90% of the
      transported P was particulate P, emphasizing the need to control erosion to
      reduce P loss. Dissolved reactive phosphorus (DRP) concentrations decreased with
      time at a specific furrow site but increased with distance down the furrow as
      contact time with soil and suspended sediment increased. The DRP concentration
      correlated better with sediment concentration than extractable furrow soil P
      concentration. However, suspended sediment concentration tended to not affect DRP
      concentration later in the irrigation (>2 h). These results indicate that the
      effects of soil P can be overshadowed by differences in flow hydraulics,
      suspended sediment loads, and non-equilibrium conditions.

PMID- 16585623
TI  - Determining phosphorus release rates to runoff from selected Alberta soils using
      laboratory rainfall simulation.
AB  - Phosphorus losses from agricultural land can cause accelerated eutrophication of
      surface water bodies. This study evaluated the use of soil test phosphorus (STP)
      levels to predict dissolved inorganic phosphorus (DIP) concentrations in runoff
      water from agricultural soils using laboratory rainfall simulation. The
      objectives of this study were to determine (i) to what extent STP concentrations
      can be used as a basis to predict P losses from Alberta soils and (ii) how
      extended rainfall simulation run times affected DIP losses. Soil samples
      collected from a total of 38 field sites, widely scattered throughout the
      southern half of Alberta, were subjected to rainfall simulation in the
      laboratory. The STP concentrations were determined using Miller-Axley, Norwest,
      Kelowna, Modified Kelowna Mehlich-III, and distilled water extraction methods.
      Each rainfall simulation event lasted for at least 90 min. Runoff samples were
      collected in time series for the duration of each simulation, during two distinct
      runoff intervals: (i) for the first 30 min of continuous runoff (T30) and (ii)
      for 40 min during runoff equilibrium (Teq). For all the STP extractants and both
      runoff intervals, the relationship with DIP-flow-weighted mean concentration
      (FWMC) was linear and highly significant with r2 values ranging from 0.74 to
      0.96. However, the slopes of the resulting regression lines were, on average,
      1.85 times greater for the T30 runoff interval over those computed for the Teq
      interval. Thus experimental methodology greatly influenced regression parameters,
      suggesting that more work was needed to verify these relationships under natural
      conditions. In addition, with many of the r2 values greater than 0.90 there would
      be little, if any, benefit derived by including soil properties in regression
      analysis.

PMID- 16585624
TI  - Measuring runoff-suspended solids using an improved turbidometer method.
AB  - Differences in particle size distribution between runoff standards and unknown
      samples affect the accuracy of estimation of total suspended solids (TSS)
      concentration using the nephelometric turbidity (NTU) method. The objective was
      to quantify the effects of a sucrose solution as suspending medium and
      contrasting particle size distribution on nephelometric turbidity and accuracy of
      TSS estimation. Nineteen benchmark soils varying in texture and color were
      divided into particle size distribution of <250 and <2000 microm. Soils from
      these two aggregate classes were then made into suspension ranging from 0.2 to 15
      g L-1 using distilled deionized water. Runoff suspensions ranging from 0.2 to 21
      g L-1 were also collected from different watersheds. Turbidity of soil and runoff
      suspensions was measured in sucrose solution and in distilled deionized water.
      The sucrose solution density ranged from 1.10 to 1.30 kg L-1. Increasing sucrose
      solution density decreased turbidity. The TSS concentration was most sensitive to
      changes in turbidity with the 1.30 kg L-1 sucrose solution. Using the 1.30 kg L-1
      sucrose solution, particle size bias and error of TSS estimates were decreased by
      at least 20% compared to distilled deionized water. Reduction in refraction index
      differences between the suspended particles and sucrose solution combined with
      reduced particle settling and reduced Brownian motion resulted in dampening the
      effects of particle size distribution. We propose a sucrose solution of 1.30 kg L
      1 as a better suspending medium to dampen the effect of particle size
      distribution and thus improve suspension TSS concentration estimation.

PMID- 16585625
TI  - Comparing carbon substrates for denitrification of subsurface drainage water.
AB  - Nitrate in water from tile drained corn (Zea mays L.) and soybean [Glycine max
      (L.) Merr.] fields in the U.S. Midwest contributes to nitrate contamination of
      surface waters. Denitrification-based biofilters are a promising strategy for
      reducing nitrate concentrations, but these systems require an external carbon
      supply to sustain denitrification. The ability of four organic materials to serve
      as carbon substrates for denitrification biofilters was evaluated in this
      laboratory study. Wood chips, wood chips amended with soybean oil, cornstalks,
      and cardboard fibers were mixed with subsoil (oxidized till) and incubated
      anaerobically for 180 d. Periodically, 15NO3-N was added to maintain nitrate N
      concentrations between 10 and 100 mg L-1. All of the materials stimulated NO3-N
      removal and the degree of removal from highest to lowest was: cornstalks,
      cardboard fibers, wood chips with oil, and wood chips alone. Analysis of 15N
      showed that immobilization and dissimilatory nitrate reduction to ammonium
      accounted for <4% of NO3-N removal in all treatments, therefore denitrification
      was the dominant NO3-N removal process. Cardboard fibers, wood chips and oil, and
      wood chips alone did not support as much denitrification as cornstalks, but their
      rates of NO3-N removal were steady and would probably continue longer than
      cornstalks. The addition of soybean oil to wood chips significantly increased
      denitrification over wood chips alone.

PMID- 16585626
TI  - Methane production during storage of anaerobically digested municipal organic
      waste.
AB  - Anaerobic digestion of source-separated municipal organic waste is considered
      feasible in Denmark. The limited hydraulic retention in the biogas reactor
      (typically 15 d) does not allow full degradation of the organic waste. Storage of
      anaerobically digested municipal organic waste can therefore be a source of
      methane (CH4) emission that may contribute significantly to the potential global
      warming impact from the waste treatment system. This study provides a model for
      quantifying the CH4 production from stored co-digested municipal organic waste
      and estimates the production under typical Danish climatic conditions, thus
      quantifying the potential global warming impact from storage of the digested
      municipal organic waste before its use on agricultural land. Laboratory batch
      tests on CH4 production as well as temperature measurements in eight full-scale
      storage tanks provided data for developing a model estimating the CH4 production
      in storage tanks containing digested municipal organic waste. The temperatures
      measured in separate storage tanks on farms receiving digested slurry were
      linearly correlated with air temperature. In storage tanks receiving slurry
      directly from biogas reactors, significantly higher temperatures were measured
      due to the high temperatures of the effluent from the reactor. Storage tanks on
      Danish farms are typically emptied in April and have a constant inflow of
      digested material. During the warmest months the content of digested material is
      therefore low, which limits the yearly CH4 production from storage.

PMID- 16585627
TI  - Poultry litter application to loblolly pine forests: growth and nutrient
      containment.
AB  - Forestland application of poultry manure offers an alternative to the
      conventional practice of pastureland application. Before such a practice is
      considered viable, however, it must be demonstrated that the forest ecosystem is
      capable of absorbing the nutrients contained in poultry manure, especially
      nitrogen (N) and phosphorus (P). From the forestry perspective, it must also be
      demonstrated that tree growth is not diminished. We investigated these questions
      using loblolly pine (Pinus taeda L.) stands growing in central Mississippi in an
      area of high poultry production. Stockpiled broiler litter was applied to newly
      thinned, 8-yr-old stands at 0, 4.6, and 18.6 dry Mg ha-1, supplying 0, 200, and
      800 kg N ha-1 and 0, 92, and 370 kg P ha-1, respectively. Levels of nitrate in
      soil water, monitored at a 50-cm depth with porous cup tension lysimeters,
      exceeded 10 mg N L-1 during the first two years after application in the 18.6 Mg
      ha-1 rate but only on two occasions in the first year for the lower rate of
      application. Phosphate was largely absent from lysimeter water in all treatments.
      Other macronutrients (K, Ca, Mg, S) were elevated in lysimeter water in
      proportion to litter application rates. Soil extractable nitrate showed similar
      trends to lysimeter water, with substantial elevation during the first year
      following application for the 18.6 Mg ha-1 rate. Mehlich III-extractable
      phosphate peaked in excess of 100 microg P g-1 soil during the third year of the
      study for the 18.6 Mg ha-1 rate. The 4.6 Mg ha-1 rate did not affect extractable
      soil P. Tree growth was increased by the poultry litter. Total stem cross
      sectional area, or basal area, was approximately 20% greater after 2 yr for both
      rates of litter application. Overall, the nutrients supplied by the 4.6 Mg ha-1
      rate were contained by the pine forest and resulted in favorable increases in
      tree growth. The higher rate, by contrast, did pose some risk to water quality
      through the mobilization of nitrate. These results show that, under the
      conditions of this study, application of poultry litter at moderate rates of
      approximately 5 Mg ha-1 to young stands of loblolly pine offers an alternative
      disposal option with minimal impacts to water quality and potential increases in
      tree growth.

PMID- 16585628
TI  - Liming poultry manures to decrease soluble phosphorus and suppress the bacteria
      population.
AB  - Stabilizing phosphorus (P) in poultry waste to reduce P losses from manured soils
      is important to protect surface waters, while pathogens in manures are an
      emerging issue. This study was conducted to evaluate CaO and Ca(OH)2 for killing
      manure bacterial populations (pathogens) and stabilizing P in poultry wastes and
      to investigate the influence on soils following amendment with the treated
      wastes. Layer manure and broiler litter varying in moisture content were treated
      with CaO and Ca(OH)2 at rates of 2.5, 5, 10, and 15% by weight. All treated
      wastes were analyzed for microbial plate counts, pH, and water-soluble phosphorus
      (WSP), while a few selected layer manures were analyzed by phosphorus X-ray
      absorption near edge structure (XANES). A loamy sand and a silt loam were amended
      with broiler litter and layer manure treated with CaO at rates of 0, 2.5, 5, 10,
      and 15% and soil WSP and pH were measured at times 1, 8, and 29 d. Liming reduced
      bacterial populations, with greater rates of lime leading to greater reductions;
      for example 10% CaO applied to 20% solids broiler litter reduced the plate counts
      from 793,000 to 6500 mL-1. Liming also reduced the WSP in the manures by over 90%
      in all cases where at least 10% CaO was added. Liming the manures also reduced
      WSP in soils immediately following application and raised soil pH. The liming
      process used successfully reduced plate counts and concerns about P losses in
      runoff following land application of these limed products due to decreased WSP.

PMID- 16585630
TI  - Peat fire effects on some properties of an artificially drained peatland.
AB  - The management of artificially drained organic soils is a very important issue,
      since the accelerated mineralization and sometimes peat fires alter physical and
      chemical properties of soils and the availability of plant nutrients. This study
      was performed to determine relatively short- and long-term effects of peat fires
      on some physical and chemical properties of soils in the artificially drained
      Gavur Lake Peatland of Turkey. To achieve this objective, measured properties of
      soils burned in 2001, burned in 1965, and unburned were compared. The results
      indicated that soil bulk density, pH, amounts of soluble salts, CaCO3, and
      concentrations of ammonium acetate-extractable (AAE) Ca, Mg, K, and Na were
      significantly higher for both sampling depths in the burned areas. The areas
      burned in 2001 had higher pH, soluble salts, and the concentrations of AAE Ca,
      Mg, and K compared with sites burned in 1965, and this was reasoned with leaching
      losses and plant uptake of these basic cations for four decades in the latter.
      Percent saturation and organic carbon contents of soils, however, were
      significantly lower in the burned areas for both sampling depths. Olsen P levels
      were not significantly different between the sites. This work clearly shows that
      alterations in soils properties with peat fires do not recover in the long term.

PMID- 16585629
TI  - Impact of diet, moisture, location, and storage on soluble phosphorus in broiler
      breeder manure.
AB  - Decreasing dietary phosphorus (P) has the potential to reduce P excreted in
      manure and therefore alleviate the environmental degradations associated with
      intensive animal farming. We evaluated reducing dietary P for broiler breeders as
      an aid to reduce manure total and water soluble phosphorus (WSP). Broiler
      breeders were fed diets high and low in dietary P, with and without phytase, from
      22 to 64 wk of age. At the end of the 42-wk production period, manure was
      collected from four locations in each two-thirds slat, one-third litter breeder
      pen: the litter scratch area, under the drinker in the slat area, under the
      feeder in the slat area, and in a clean area of the slat area away from feeder or
      drinker. After the initial sampling, all manure was removed from pens and
      representative samples were stored for 6 mo with and without feed mixed in to
      simulate the effect of spilled feed. Total P was determined on all pen samples,
      and moisture and WSP determined on the pen and stored samples. The manure
      collected under the drinker had much greater moisture due to spilled water. This
      was associated with much greater WSP in this location, showing the importance of
      good water management. The manure from under the feeder had similar WSP as manure
      from the clean area, so spilled feed did not significantly affect WSP. Dietary
      phytase either had no effect or significantly decreased manure WSP. However,
      addition of dietary phytase to the feed led to slightly elevated manure moisture.
      Since moisture was correlated with manure WSP this may explain some of the
      variability in WSP results between studies. Over 6 mo of storage WSP increased
      and generally followed the same ranking order at 168 d as at 1 d among the
      dietary treatments (high>high+phytase>low>low+phytase). Combining decreased
      dietary P and phytase reduced both manure total P and WSP by 42%. As total P and
      WSP are indicators of the long and short term impacts manure applications can
      have on P losses from manured soils, diet modification should be seen as
      environmentally beneficial.

PMID- 16585631
TI  - Human immunodeficiency virus and hepatitis virus infection in correctional
      institutions in Africa: is this the neglected source of an epidemic?

PMID- 16585632
TI  - Cytomegalovirus infection in burns: a review.
AB  - Sepsis is responsible for significant morbidity and mortality in patients
      suffering from severe burn injuries. Burn patients are known to be
      immunocompromised, and it is generally accepted that the immunosuppressed patient
      may experience human cytomegalovirus (HCMV) infection and disease. Review of the
      very limited available literature identifies a seroconversion rate of between 18
      and 22% for burn patients who were seronegative for HCMV prior to suffering their
      burn injury. Furthermore, approximately 50% of HCMV antibody-positive patients
      may reactivate. Blood products and allografted skin have clinically been
      identified as possible sources of HCMV transmission in burn patients. Experience
      in the treatment of infection or disease in burn patients is very scarce and
      limited to immunoglobulin therapy. Animal experiments have demonstrated that
      murine cytomegalovirus (MCMV)-seropositive skin grafts are able to infect
      immunodeficient mice as well as burned mice. Murine studies have also
      demonstrated that infection with MCMV enhances susceptibility to secondary
      bacterial infection and increases mortality in these animals. Burned mice
      challenged with MCMV have a significantly higher level of bacterial translocation
      to mesenteric lymph nodes than either control thermally injured mice without MCMV
      inoculation or non-burned mice injected with MCMV alone. In summary, it remains
      controversial whether HCMV infection per se alters outcome for the majority of
      burn patients. Subgroups of severely burned, seronegative patients may benefit
      from blood products and skin from seronegative donors. Antiviral strategies are
      not yet evaluated for the burn patient. Further investigations utilizing modern
      diagnostic techniques seem necessary.

PMID- 16585633
TI  - Modulation of crystalline Proteus mirabilis biofilm development on urinary
      catheters.
AB  - The crystalline biofilms formed by Proteus mirabilis can seriously complicate the
      care of patients undergoing long-term bladder catheterization. The generation of
      alkaline urine by the bacterial urease causes calcium and magnesium phosphates to
      precipitate from urine and accumulate in the catheter biofilm, blocking the flow
      of urine from the bladder. The pH at which these salts crystallize from a urine
      sample, the nucleation pH (pH(n)), can be elevated by diluting the urine and by
      increasing its citrate content. The aim of this study was to examine whether
      manipulation of pH(n) in these ways modulated the rate at which crystalline
      biofilm developed. Experiments in laboratory models of the catheterized bladder
      infected with P. mirabilis showed that when the bladder was supplied with a
      concentrated urine (pH(n) 6.7) at a low fluid output (720 ml per 24 h), catheters
      blocked at 19-31 h. Diluting this urine 1:4 increased the pH(n) to 7.5 and models
      supplied with this urine at 2880 ml per 24 h took 110-137 h to block. When models
      were supplied with urine containing citrate at 1.5 mg ml(-1) or above (pH(n) 8.3
      9.1), the catheters drained freely for the full 7 day experimental period.
      Scanning electron microscopy revealed that the catheter biofilms that developed
      in urine with high pH(n) values were devoid of crystalline formations. These
      observations should encourage a clinical trial to examine the effect of
      increasing a patient's fluid intake with citrate-containing drinks on the
      encrustation and blockage of catheters.

PMID- 16585634
TI  - Clostridium perfringens phospholipase C-induced platelet/leukocyte interactions
      impede neutrophil diapedesis.
AB  - Clostridium perfringens gas gangrene is a fulminant necrotizing infection in
      which inflammatory cells are notably absent from infected tissues but are often
      massed within adjacent vessels. It has been shown that C. perfringens
      phospholipase C (PLC) stimulates formation of large intravascular
      platelet/leukocyte complexes and that PLC-induced activation of platelet
      gpIIbIIIa plays a major role. In vivo, such aggregates contribute to
      microvascular thrombosis and ischaemic necrosis of tissue. However, the effects
      of adherent platelets on neutrophil diapedesis have not been established. The
      present work investigated (1) the contribution of platelet P-selectin (CD62P) to
      PLC-induced cellular complex formation and (2) the effects of platelet adhesion
      on neutrophil diapedesis. The effects of anti-gpIIbIIIa and anti-CD62P strategies
      on PLC-induced complex formation were measured by flow cytometry and followed by
      light microscopy. Both platelet gpIIbIIIa and CD62P contributed to the formation
      of platelet/leukocyte complexes. Specifically, gpIIbIIIa mediated the formation
      of large platelet/platelet aggregates that were tethered to the leukocyte
      principally via CD62P. Neutrophil diapedesis, quantified by a transendothelial
      cell migration assay and visualized by electron microscopy, was significantly
      reduced (>60%) by the adherence of large platelet aggregates. It was concluded
      that the absence of a tissue inflammatory response in C. perfringens gas gangrene
      is due, in part, to impaired neutrophil mobility caused by large aggregates of
      adherent platelets induced by PLC. Further, an adjunctive immunotherapeutic
      strategy targeting both gpIIbIIIa and CD62P may improve the tissue inflammatory
      response, prevent vascular occlusion, maintain tissue viability, and reduce the
      need for radical amputation in patients with clostridial gas gangrene.

PMID- 16585635
TI  - Dependence of the lethal effect of pore-forming haemolysins of Gram-positive
      bacteria on cytolytic activity.
AB  - Among bacterial haemolysins, cholesterol-dependent cytolysins (CDCs) produced by
      various Gram-positive bacteria are known to exhibit a lethal activity in mice. In
      this study, recombinant CDCs of streptolysin O, pneumolysin, ivanolysin O,
      listeriolysin O and several listeriolysin O mutants were constructed and the
      relationship between cytolytic activity and the lethal activity of each
      recombinant protein in mice was examined. Specific activity for cytolysis was
      determined by a quantitative haemolytic assay. Each protein was injected
      intravenously into mice and the lethal activity was evaluated by measuring the
      time until death of the mice. The four full-length CDC proteins exhibited lethal
      activity and their activities were highly proportional to their cytolytic
      activities. Inhibition of haemolytic activity resulted in the loss of lethal
      activity and non-haemolytic mutants of listeriolysin O did not exhibit any lethal
      activity. These data clearly indicate that the lethal effect of CDC proteins is
      dependent on the cytolytic activity.

PMID- 16585636
TI  - Association between the Phe206Leu polymorphism of L-selectin and brucellosis.
AB  - Brucellosis remains a major zoonosis worldwide; therefore, better understanding
      of its immunology is a priority for the development of new therapeutic and
      vaccination strategies. Genetic factors appear to have an important role in the
      pathogenesis of infectious diseases such as brucellosis. Adhesion molecules, such
      as members of the selectin family, participate in the interaction between
      leukocytes and the endothelium, as well as in inflammatory cell recruitment. The
      impact of L-selectin polymorphisms on brucellosis has not so far been
      investigated. The aim of this study was to assess an L-selectin Phe206Leu (F206L)
      polymorphism in patients with active brucellosis, and to analyse its possible
      relationship with disease progression. A case-control association study was
      carried out on 619 subjects, including 374 patients with brucellosis and 245 age-
      and sex-matched healthy controls. Genomic DNA was isolated, and amplification of
      L-selectin genomic regions was performed by PCR incorporating sequence-specific
      primers (PCR-SSP) to distinguish the genotypes. The frequencies of the F206L
      polymorphism were studied. A significant difference in F206L polymorphism was
      found between patients with brucellosis and controls. The 206Leu allele was more
      frequent in patients than in healthy individuals (36.6 versus 28 %, P=0.003). In
      addition, there was an association between the presence of the 206Leu allele and
      a relapse of brucellosis (odds ratio 6.53, 95 % confidence interval 1.5-28.8,
      P=0.005). The higher frequency of L-selectin genotypes in patients with
      brucellosis than in control individuals, as well as the association between the
      206Leu allele and the occurrence of brucellosis relapse, suggest that the F206L
      polymorphism could make individuals more vulnerable to brucellosis.

PMID- 16585637
TI  - Characterization of bovine and human group B streptococci isolated in Turkey.
AB  - In the study, group B streptococci (GBS) isolated from bovines and humans in and
      around Van, eastern Turkey, were serotyped, and their haemagglutination and
      lectin-agglutination properties were also determined. This study is the first
      epidemiological survey of GBS serotypes performed in Turkey. A total of 148 GBS
      isolates, 76 from bovine milk and 72 from women attending a maternity polyclinic,
      were examined by co-agglutination, slide haemagglutination and slide lectin
      agglutination tests. By the co-agglutination test, 34 (44.7%) of bovine isolates
      and 49 (68%) of human isolates could be serotyped. In bovine isolates, type VII
      (11.8%), III (10.5%), Ic (6.5%) and VIII (3.9%) were the most frequently detected
      serotypes. The most frequent human serotypes were Ic (33.3%), IV (8.3%), VIII
      (6.9%), V (5.5%) and R (5.5%). In the haemagglutination test using rabbit
      erythrocytes, 23 (33.3%) bovine and 15 (23.4%) human isolates were found to be
      positive. The bovine GBS isolates showed a significant positive agglutination
      reaction with Dolichos biflorus lectin (30.4 %), whereas the human GBS isolates
      were found to be positive for Arachis hypogea (18.8%) and Canavalia ensiformis
      (37.5%) lectins. The treatment of GBS with trypsin was also found to be important
      for the demonstration of the haemagglutination and lectin-agglutination
      properties of GBS. The results of the study provide data on serotype distribution
      and the formulation of a possible GBS vaccine in Turkey, and the lectin
      agglutination tests may also be useful for differentiating bovine and human GBS
      strains.

PMID- 16585638
TI  - Staphylococcus equorum and Staphylococcus succinus isolated from human clinical
      specimens.
AB  - A polyphasic identification approach was applied to a group of 11 novobiocin
      resistant staphylococci isolated from human clinical materials. Phenotypic
      characteristics obtained by both commercial and conventional tests assigned eight
      strains as Staphylococcus xylosus and three strains as ambiguous S.
      xylosus/Staphylococcus equorum. In contrast to biotyping, ribotyping with EcoRI
      and HindIII restriction endonucleases and whole-cell protein fingerprinting
      assigned six analysed strains as S. equorum, and five strains as Staphylococcus
      succinus. Confirmation of the identification was done by partial 16S rRNA gene
      sequencing and S. equorum isolates were verified by a PCR assay targeting the
      sodA gene. From the data it has been implied that ribotyping and whole-cell
      protein analysis can be used to differentiate between the biochemically almost
      indistinguishable species S. xylosus, S. equorum and S. succinus. The present
      study confirms what is believed to be the first occurrence of S. equorum in a
      relevant human clinical material in the Czech Republic and describes what is
      believed to be the first-ever isolation of S. succinus from human clinical
      material.

PMID- 16585639
TI  - Diagnostic application of genotypic identification of mycobacteria.
AB  - This study evaluated conventional methods, GLC and three molecular tests,
      including 16S rRNA sequencing, for the identification of mycobacteria, and the
      experiences of the authors with the integration of these methods into a
      diagnostic clinical laboratory were also recorded. Of 1067 clinical isolates of
      mycobacteria identified by conventional tests, 365 were tested by Accuprobe
      hybridization assays and PCRs specific for Mycobacterium tuberculosis (MTB)
      complex or Mycobacterium avium complex (MAC), 202 were tested by 16S rRNA
      sequencing, and 142 were tested by GLC. Three runs of all tests were performed on
      a weekly basis. The identifications for 209 MTB complex and 118 MAC isolates
      obtained by species-specific PCR were in complete agreement with AccuProbe
      hybridization and conventional test results. The 16S rRNA sequence-based
      identification, at a similarity of > or =99 %, for 132 of 142 isolates was
      concordant with the identifications made by the biochemical methods, and for 134
      isolates was concordant with the identifications made by GLC at species, group or
      complex level. 16S rRNA sequencing resulted in fewer incorrectly identified or
      unidentified organisms than GLC or conventional tests. For the slowly growing non
      tuberculous mycobacteria, the mean turnaround times for identification were 4-5
      days for 16S rRNA sequencing, 14-29 days for GLC and 22-23 days for conventional
      methods. Considering the large proportion of some species among clinical
      isolates, a strategy of initial screening with species-specific PCR (or AccuProbe
      assays) for the MTB complex and MAC, followed by direct sequencing of the strains
      that yield negative results, should make 16S rRNA sequencing more affordable for
      routine application in diagnostic laboratories.

PMID- 16585640
TI  - Evaluation of a newly developed down-flow immunoassay for detection of serum
      mannan antigens in patients with candidaemia.
AB  - A down-flow immunoassay has been developed to detect serum mannan antigens, and
      the test was recently marketed as the Unimedi Candida monotest. Using 251 serum
      samples from 105 patients with candidaemia, a comparison of the Unimedi Candida
      monotest with the Cand-Tec latex agglutination test and 2 microplate enzyme
      immunoassay tests (Platelia Candida Ag test and Unimedi Candida) was conducted.
      One hundred and seventy-five febrile patients without clinical and
      microbiological evidence of fungal infections and pneumocytosis were examined as
      controls. The Cand-Tec test had a sensitivity of 38% and a specificity of 82%.
      The sensitivity and specificity of the Platelia Candida Ag test, the Unimedi
      Candida and the Unimedi Candida monotest were 53 and 92%, 69 and 89% and 82 and
      96%, respectively. The sensitivity of the Unimedi Candida monotest was
      significantly (P<0.01) higher than that of the Plateria Candida Ag test for
      diagnosing candidaemia caused by Candida parapsilosis. The beta-D-glucan assay
      had a high sensitivity of 95%, with a specificity of 84%. Of 74 patients with
      candidaemia whose sera were available before or on positive blood culture
      sampling, 29 (39%), 38 (51%) and 48 (65%) patients had antigenemia detected using
      the Platelia Candida Ag test, the Unimedi Candida and the Unimedi Candida
      monotest, respectively. The Unimedi Candida monotest seems to be a promising tool
      for the early diagnosis of invasive candidiasis, because the test was sensitive,
      simple, rapid (approx. 1 h) and cost-effective.

PMID- 16585641
TI  - Intraserotype diversity among Argentinian verocytotoxigenic Escherichia coli
      detected by random amplified polymorphic DNA analysis.
AB  - Most cases of diarrhoea-associated haemolytic uraemic syndrome (HUS) are caused
      by verocytotoxin-producing Escherichia coli (VTEC). Argentina has the highest
      worldwide incidence of HUS, but with a lower incidence of VTEC O157 : H7 serotype
      than non-Latin American countries. A large number of VTEC serotypes have been
      isolated from cattle and cattle-derived food products in Argentina. The aim of
      this work was to study intraserotype genetic diversity among these VTEC strains
      by random amplification of polymorphic DNA (RAPD). Strains were selected that
      belonged to the same serotype, but had been isolated from different sources
      (cattle and meat). Intraserotype genetic diversity was detected among strains
      belonging to O20 : H19, O113 : H21, O117 : H7, O157 : H7, O171 : H2 and O174 :
      H21, but only one RAPD profile corresponded to strains belonging to O91 : H21,
      although these isolates were from different sources.

PMID- 16585642
TI  - Using real-time PCR to specifically detect Burkholderia mallei.
AB  - Burkholderia mallei is the causative agent of human and animal glanders and is a
      category B biothreat agent. Rapid diagnosis of B. mallei and immediate
      prophylactic treatment are essential for patient survival. The majority of
      current bacteriological and immunological techniques for identifying B. mallei
      from clinical samples are time-consuming, and cross-reactivity with closely
      related organisms (i.e. Burkholderia pseudomallei) is a problem. In this
      investigation, two B. mallei-specific real-time PCR assays targeting the B.
      mallei bimA(ma) gene (Burkholderia intracellular motility A; BMAA0749), which
      encodes a protein involved in actin polymerization, were developed. The PCR
      primer and probe sets were tested for specificity against a collection of B.
      mallei and B. pseudomallei isolates obtained from numerous clinical and
      environmental (B. pseudomallei only) sources. The assays were also tested for
      cross-reactivity using template DNA from 14 closely related Burkholderia species.
      The relative limit of detection for the assays was found to be 1 pg or 424 genome
      equivalents. The authors also analysed the applicability of assays to detect B.
      mallei within infected BALB/c mouse tissues. Beginning 1 h post aerosol exposure,
      B. mallei was successfully identified within the lungs, and starting at 24 h post
      exposure, in the spleen and liver. Surprisingly, B. mallei was not detected in
      the blood of acutely infected animals. This investigation provides two real-time
      PCR assays for the rapid and specific identification of B. mallei.

PMID- 16585643
TI  - Sensitivity of three serum antibody tests in a large outbreak of Legionnaires'
      disease in the Netherlands.
AB  - In 1999, an outbreak involving 188 patients with Legionnaires' disease (LD)
      occurred at a flower show in the Netherlands. This large outbreak provided the
      opportunity to evaluate serum antibody tests to assay anti-Legionella
      pneumophila, since limited data are available on the sensitivity of these tests.
      The sensitivities of an indirect serotype 1-6 immunofluorescence antibody test
      (IFAT), a rapid micro-agglutination test (RMAT) IgM serotype 1 antibody assay,
      and an ELISA to detect IgM and IgG serotype 1-7 antibodies, were evaluated using
      serum samples from LD patients related to the 1999 outbreak. Sensitivity was
      calculated using positive culture and/or a positive urinary antigen test as the
      gold standard in outbreak-related patients with radiographically confirmed
      pneumonia who fulfilled the epidemiological criteria. The IFAT, RMAT and ELISA
      showed sensitivities of 61, 44 and 64%, respectively. The sensitivity of the
      three tests combined was 67%. In epidemic situations, however, high standing
      titres may be included in the laboratory evidence of LD cases. In the study
      population, high standing titres were found in 16% of cases. If the presence of
      high standing antibody titres was added to the criteria of a positive test, the
      sensitivities of IFAT, RMAT and ELISA were 86, 48 and 75%, respectively. The
      sensitivity was 91% for all tests combined. The higher sensitivity for the
      combined use of tests is offset by a reduction in specificity to 97.6%. The
      results of this study indicate that using a combination of serologic tests in
      pneumonia patients suspected to have LD does not substantially improve
      sensitivity. The results suggest that in the microbiological diagnosis of LD,
      both IFAT and ELISA are reasonably sensitive assays. In an epidemic situation,
      both tests are highly sensitive, the IFAT more so than the ELISA.

PMID- 16585644
TI  - Increase in numbers of beta-lactam-resistant invasive Streptococcus pneumoniae in
      Brazil and the impact of conjugate vaccine coverage.
AB  - A comprehensive investigation of invasive Streptococcus pneumoniae was carried
      out in Brazil as part of the programme of the national epidemiological
      surveillance system. The investigation provided data on the trends of resistance
      to antimicrobial agents. A total of 6470 isolates of S. pneumoniae collected in
      the country from 1993 to 2004 were tested. During this period of time, the number
      of penicillin-resistant strains rose from 10.2 to 27.9%. The proportions of
      intermediate and high-level resistant strains in 1993, which were 9.1 and 1.1%,
      respectively, rose to 22.0 and 5.9% in 2004. Geometric mean MICs for penicillin
      increased after the year 2000, to 0.19 microg ml(-1) in 2004; most of these
      isolates were from patients with pneumonia and from children under 5 years old,
      and belonged to serotype 14. There was a significant increase in the number of
      isolates belonging to serotypes included in the 7-valent conjugate vaccine from
      children under 5 years old: from 48.6% in 1993 to 69.6% in 2004, mainly related
      to an increase in the frequency of serotype 14 isolates. From 2000 to 2004,
      meningitis isolates showed higher resistance rates to cefotaxime (2.6%) compared
      to non-meningitis isolates (0.7%); percentages of isolates resistant to
      trimethoprim-sulfamethoxazole, tetracycline, erythromycin, chloramphenicol and
      rifampicin were 65, 14.6, 6.2, 1.3 and 0.7 %, respectively. No levoflaxin
      resistance was observed. Multidrug resistance was identified in 4.6% of isolates,
      of which 3.8% were resistant to three classes, 0.7% to four classes and 0.1% to
      five classes of antimicrobial agent. The study provides valuable information that
      may support empirical antimicrobial therapy for severe S. pneumoniae infections
      in Brazil, and emphasizes the need for conjugate pneumococcal vaccination.

PMID- 16585645
TI  - Distribution and characterization of integrons in various serogroups of Vibrio
      cholerae strains isolated from diarrhoeal patients between 1992 and 2000 in
      Kolkata, India.
AB  - A total of 133 clinical strains of Vibrio cholerae comprising 44 strains of O1,
      45 strains of O139 and 44 strains of non-O1, non-O139 serogroups isolated from
      hospitalized patients in Kolkata, India, from 1992 to 2000 was examined for the
      presence of class 1, 2 and 4 integrons. By PCR and DNA sequencing, seven strains
      of O1, one strain of O139 and six strains of non-O1, non-O139 serogroups were
      found to contain class 1 integron-harbouring genes aadA1, aadA2 (encoding
      resistance to streptomycin and spectinomycin), blaP1 (resistance to beta
      lactams), aar-3 (resistance to rifampicin), aacA4 (resistance to kanamycin and
      gentamicin), and dfrA1 and dfrA15 (resistance to trimethoprim). Most strains
      produced one or two bands using primers specific for the amplification of the
      variable region where the antibiotic-resistance genes are located, and their
      sizes ranged from 700 to 1250 bp. However, one strain of V. cholerae O1 isolated
      in 1994 gave a 2483 bp fragment, the largest fragment so far found in a class 1
      integron of V. cholerae O1. No strain was positive for the intI2 gene. All V.
      cholerae strains, regardless of serogroup, were positive for the intI4 gene by
      PCR and using a colony hybridization test. Amplification of the intI4 gene by PCR
      yielded a 2200 bp fragment (1260 bp larger than the expected size) from three V.
      cholerae O139 strains isolated in 1999. Sequence analysis of this amplicon
      revealed an insertion of IS1359 in the middle of the intI4 gene. These data
      indicate that a class 1 integron is present in some clinical strains of V.
      cholerae isolated in Kolkata, India, and that a class 4 integron is ubiquitously
      distributed among V. cholerae strains regardless of serogroup.

PMID- 16585646
TI  - Invasive multidrug-resistant non-typhoidal Salmonella infections in Africa:
      zoonotic or anthroponotic transmission?
AB  - In Africa, multidrug-resistant non-typhoidal salmonellae (NTS) are one of the
      leading causes of morbidity and high mortality in children under 5 years of age,
      second in importance only to pneumococcal disease. The authors studied NTS
      isolates from paediatric admissions at two hospitals in Nairobi, Kenya, and
      followed the index cases to their homes, where rectal swabs and stools from
      parents and siblings, and from animals in close contact, were obtained. The
      majority of NTS obtained from cases were Salmonella enterica serotype Typhimurium
      (106 out of 193; 54.9%) and Salmonella enterica serotype Enteritidis (64; 33.2%),
      a significant proportion (34.2%) of which were multiply resistant to three or
      more antibiotics, including ampicillin, tetracycline, cotrimoxazole and
      chloramphenicol. Only 23.4% of NTS were fully susceptible to all 10 antibiotics
      tested. Of the 32 NTS obtained from contacts (nine adults and 23 children) at the
      homes of index cases, 21 (65.6%) isolates were similar by antibiotic
      susceptibility profiles and plasmid content, and their XbaI- and SpeI-digested
      chromosomal DNA patterns were indistinguishable from those of the corresponding
      index cases. Only three out of 180 (1.7%) samples from environmental sources,
      including animals, soil, sewers and food, contained NTS matching those from
      corresponding index cases. The carriage of NTS in an asymptomatic population was
      represented by 6.9% of human contacts from 27 out of 127 homes sampled. This
      population of carriers may represent an important reservoir of NTS that would
      play a significant role in the epidemiology of community-acquired NTS bacteraemia
      in children.

PMID- 16585647
TI  - Prevalence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus
      and syphilis among prison inmates and officers at Nsawam and Accra, Ghana.
AB  - Although the high prevalence of blood-borne viral infections and syphilis in
      correctional facilities has been well documented globally, such data are sparse
      from Africa, and there has been no such data from Ghana. This study sought to
      estimate the prevalence of human immunodeficiency virus (HIV), hepatitis B virus
      (HBV), hepatitis C virus (HCV) and syphilis among prison inmates and officers at
      prisons in Nsawan and Accra, Ghana. Prisoners and officers in 3 of the 46 prisons
      in Ghana were surveyed from May 2004 to May 2005. Subjects voluntarily completed
      a risk-factor questionnaire and provided blood specimens for unlinked anonymous
      testing for the presence of antibodies to HIV, HCV and Treponema pallidum, the
      causative agent of syphilis, and the surface antigen of hepatitis B virus
      (HBsAg). Almost 16% (3770) of the total of 23,980 prison inmates in Ghana were
      eligible, and 281 (7.5%) of those eligible took part, whilst almost 23% (1120) of
      the total of 4910 prison officers were eligible, and 82 (7.3%) of those eligible
      took part. For the 281 inmates tested, HIV seroprevalence was 19.2%, 17.4% had
      HBsAg, HCV seroprevalence was 19.2% and reactive syphilis serology was noted in
      11%. For the 82 officers tested, HIV seroprevalence was 8.5%, 3.7% had HBsAg, HCV
      seroprevalence was 23.2% and reactive syphilis serology was noted in 4.9%. The
      data indicate a higher prevalence of HIV and HCV in correctional facilities (both
      prison inmates and officers) than in the general population in Ghana, suggesting
      their probable transmission in prisons in Ghana through intravenous drug use,
      unsafe sexual behaviour and tattooing as pertains to prisons worldwide.

PMID- 16585648
TI  - Mutations in mutT genes of Mycobacterium tuberculosis isolates of Beijing
      genotype.
AB  - Missense alterations in genes mutT4 and mutT2, which encode DNA repair enzymes,
      were sequenced from 30 clinical isolates of Mycobacterium tuberculosis of Beijing
      genotype, mostly from patients with primary tuberculosis, to evaluate their
      contribution to anti-mycobacterial drug resistance. The mutation Arg to Gly at
      codon position 48 (CGG to GGG) of mutT4 was found in 21 isolates; of these, 16
      isolates also harboured the mutation Gly to Arg at position 58 (GGA to CGA) of
      mutT2. No statistically significant association was found between mutT4 and mutT2
      mutations, and drug resistance. Furthermore, no mutations in mutT4 or mutT2 were
      found in any of 24 isolates resistant to multiple drugs, nor in 28 anti
      mycobacterial drug-susceptible isolates of different genotypes. These data
      confirm that the polymorphism of mutT genes is characteristic and unique to the
      Beijing phylogenetic lineage. The mutator phenotype does not appear to increase
      prevalence of drug resistance, but further studies are required to investigate
      the mutation rates of Beijing isolates in response to drug exposure.

PMID- 16585649
TI  - Potential role of Clostridium difficile as a cause of duodenitis-proximal
      jejunitis in horses.
AB  - Duodenitis-proximal jejunitis (DPJ) is an idiopathic condition in the horse
      characterized by inflammation and oedema of the duodenum and proximal jejunum.
      Clinical signs include colic, ileus, depression, fluid accumulation in the small
      intestine and stomach, and endotoxaemia. The objective of this study was to
      investigate prospectively the role of Clostridium difficile in this idiopathic
      disease. Nasogastric reflux from 10 consecutive cases with DPJ and 16 consecutive
      horses with other causes of nasogastric reflux was cultured for C. difficile,
      other Clostridium spp., and Salmonella. Toxigenic strains of C. difficile were
      isolated from 10/10 (100%) of horses with DPJ and 1/16 controls (P<0.0001). No
      other known pathogenic clostridia were isolated from either group. Results of
      this study suggest that C. difficile might be an important cause of this
      syndrome.

PMID- 16585650
TI  - Identification of oral bacteria associated with crevicular epithelial cells from
      chronic periodontitis lesions.
AB  - Bacterial invasion of host epithelial cells plays an important role in the
      pathogenesis of periodontal diseases; however, the interactions between
      subgingival species and the gingival crevice cells are not fully understood. This
      study determined the prevalence of a group of oral bacterial species on or in
      epithelial cells derived from periodontal pockets and the gingival crevice of
      subjects with periodontitis. Samples of epithelial cells were obtained from 120
      sites with periodontal pockets > or =4 mm and 92 periodontally healthy sites from
      49 patients (mean age 46.3+/-1.4 years; 43% males) with chronic periodontitis.
      Bacteria in or on epithelial cells were separated from unattached bacteria by
      Percoll density-gradient centrifugation. The presence and levels of 33 oral
      species were determined in epithelial cell samples by whole genomic DNA probes
      and the checkerboard method. The most frequently detected species were
      Porphyromonas gingivalis (42%), Treponema denticola (38%), Prevotella intermedia
      (37%), Streptococcus intermedius (36%), Campylobacter rectus (35%), Streptococcus
      sanguinis (35%) and Streptococcus oralis (34%). Species of Actinomyces were found
      in low prevalence and levels. The data indicated that there were more micro
      organisms on or in epithelial cells obtained from periodontal pockets than from
      healthy sulci; however, no significant differences regarding the percentage and
      level of any specific species were found between these sites. Veillonella
      parvula, S. oralis, Streptococcus gordonii and Streptococcus mitis tended to be
      more prevalent in sites without disease. These findings demonstrated that a wide
      range of oral species may be detected on or in crevicular epithelial cells from
      sites with periodontitis and from periodontally healthy sulci.

PMID- 16585651
TI  - Prevalence of Bacteroides and Prevotella spp. in ulcerative colitis.
AB  - The resident bacterial flora of the large intestine has become increasingly
      recognized as an essential component in the pathogenesis of ulcerative colitis
      (UC). However, it is still not known whether the bacterial flora in general or
      certain bacterial species of the intestinal microbial flora contribute to the
      pathogenesis of the disease. In order to investigate the composition of the
      mucosa-associated microbial flora in UC, mucosal tissue samples from patients
      with active UC and from control subjects with non-inflammatory conditions were
      analysed and compared. To cover the whole spectrum of intestinal bacteria and to
      circumvent the known bias introduced by culture-based techniques, comparative 16S
      rRNA gene sequence analysis was used to determine the bacterial composition in
      the mucosal tissue samples. The investigation revealed an abundance of sequences
      from Bacteroides spp. and Prevotella spp. in the mucosal tissue of patients with
      UC compared with individuals showing no signs of disease. The higher incidence of
      populations of members of the Bacteroidetes in UC suggests that these may have an
      influence on the pathogenesis of the disease.

PMID- 16585652
TI  - Prevalence and temporal stability of selected clostridial groups in irritable
      bowel syndrome in relation to predominant faecal bacteria.
AB  - The differences in faecal bacterial population between irritable bowel syndrome
      (IBS) and control subjects have been reported in several studies. The aim of the
      present study was to compare the predominant and clostridial faecal microbiota of
      IBS subjects and healthy controls by applying denaturing gradient gel
      electrophoresis (DGGE) and a recently developed multiplexed and quantitative
      hybridization-based technique, transcript analysis with the aid of affinity
      capture (TRAC). According to the results, the studied clostridial groups
      (Clostridium histolyticum, Clostridium coccoides-Eubacterium rectale, Clostridium
      lituseburense and Clostridium leptum) represented the dominant faecal microbiota
      of most of the studied subjects, comprising altogether 29-87% of the total
      bacteria as determined by the hybridized 16S rRNA. The C. coccoides-E. rectale
      group was the dominant subgroup of clostridia, contributing a mean of 43% of the
      total bacteria in control subjects and 30% (constipation type) to 50% (diarrhoea
      type) in different IBS symptom category subjects. The proportion of the C.
      coccoides-E. rectale group was found to be significantly lower in the
      constipation-type IBS subjects than in the control subjects. DNA-based PCR-DGGE
      and RNA-based RT-PCR-DGGE analyses targeted to the predominant bacterial
      population showed considerable biodiversity as well as uniqueness of the
      microbiota in each subject, in both control and IBS subject groups. The RT-PCR
      DGGE profiles of the IBS subjects further indicated higher instability of the
      bacterial population compared to the control subjects. The observations suggest
      that clostridial microbiota, in addition to the instability of the active
      predominant faecal bacterial population, may be involved in IBS.

PMID- 16585653
TI  - Aspergillus fumigatus tricuspid native valve endocarditis in a non-intravenous
      drug user.
AB  - Invasive aspergillosis is an emerging infection mainly affecting
      immunocompromised patients. This report details a case of Aspergillus fumigatus
      tricuspid native valve endocarditis complicated by recurrent septic pulmonary
      emboli in a young, non-intravenous drug user. He was treated by surgical
      resection of the posterior leaflet of the tricuspid valve and the vegetations, as
      well as by valvuloplasty, which was followed by a combination of liposomal
      amphotericin B and voriconazole as acute-phase therapy and voriconazole alone as
      suppression therapy.

PMID- 16585654
TI  - Detection and quantification of Legionella pneumophila DNA in serum: case reports
      and review of the literature.
AB  - Legionella pneumonia can be difficult to diagnose. Existing laboratory tests all
      have shortcomings, especially the ability to diagnose all Legionella spp. at an
      early stage. Detection of Legionella DNA in serum can be a valuable tool for the
      diagnosis of Legionnaires' disease (LD). This report describes two patients with
      LD diagnosed by PCR using serum samples. In addition, quantification of L.
      pneumophila DNA using real-time PCR during the course of illness was carried out.
      The results obtained mirrored both the clinical condition and C-reactive protein
      values during the course of the illness. Quantification of Legionella DNA in
      serum using real-time PCR could be a valuable tool to monitor the effects of
      antimicrobial therapy in patients with LD.

PMID- 16585655
TI  - Class 2 integrons in Vibrio cholerae.

PMID- 16585656
TI  - Summaries for patients. Improvements in diabetes care in the United States, 1988
      2002.

PMID- 16585657
TI  - Summaries for patients. The effects of lifestyle changes on long-term blood
      pressure control.

PMID- 16585658
TI  - Summaries for patients. Outcomes of patients with mild depression after 1 year.

PMID- 16585659
TI  - Summaries for patients. Twenty-four cases of pneumonitis in kidney
      transplantation recipients receiving sirolimus.

PMID- 16585660
TI  - Improvements in diabetes processes of care and intermediate outcomes: United
      States, 1988-2002.
AB  - BACKGROUND: Progress of diabetes care is a subject of public health concern.
      OBJECTIVE: To assess changes in quality of diabetes care in the United States by
      using standardized measures. DESIGN: National population-based, serial cross
      sectional surveys. SETTING: National Health and Nutrition Examination Survey
      (1988-1994 and 1999-2002) and the Behavioral Risk Factor Surveillance System
      (1995 and 2002). PARTICIPANTS: Survey participants 18 to 75 years of age who
      reported a diagnosis of diabetes. MEASUREMENTS: Glycemic control, blood pressure,
      low-density lipoprotein (LDL) cholesterol level, annual cholesterol level
      monitoring, and annual foot and dilated eye examination, as defined by the
      National Diabetes Quality Improvement Alliance measures. RESULTS: In the past
      decade, the proportion of persons with diabetes with poor glycemic control
      (hemoglobin A1c > 9%) showed a nonstatistically significant decrease of 3.9% (95%
      CI, -10.4% to 2.5%), while the proportion of persons with fair or good lipid
      control (LDL cholesterol level < 3.4 mmol/L [<130 mg/dL]) had a statistically
      significant increase of 21.9% (CI, 12.4% to 31.3%). Mean LDL cholesterol level
      decreased by 0.5 mmol/L (18.8 mg/dL). Although mean hemoglobin A1c did not
      change, the proportion of persons with hemoglobin A(1c) of 6% to 8% increased
      from 34.2% to 47.0%. The blood pressure distribution did not change. Annual lipid
      testing, dilated eye examination, and foot examination increased by 8.3% (CI,
      4.0% to 12.7%), 4.5% (CI, 0.5% to 8.5%), and 3.8% (CI, -0.1% to 7.7%),
      respectively. The proportion of persons reporting annual influenza vaccination
      and aspirin use improved by 6.8 percentage points (CI, 2.9 percentage points to
      10.7 percentage points) and 13.1 percentage points (CI, 5.4 percentage points to
      20.7 percentage points), respectively. LIMITATIONS: Data are self-reported, and
      the surveys do not have all National Diabetes Quality Improvement Alliance
      indicators. CONCLUSION: Diabetes processes of care and intermediate outcomes have
      improved nationally in the past decade. But 2 in 5 persons with diabetes still
      have poor LDL cholesterol control, 1 in 3 persons still has poor blood pressure
      control, and 1 in 5 persons still has poor glycemic control.

PMID- 16585661
TI  - Therapy modifications in response to poorly controlled hypertension,
      dyslipidemia, and diabetes mellitus.
AB  - BACKGROUND: Poorly controlled cardiovascular risk factors are common. Evaluating
      whether physicians respond appropriately to poor risk factor control in patients
      may better reflect quality of care than measuring proportions of patients whose
      conditions are controlled. OBJECTIVES: To evaluate therapy modifications in
      response to poor control of hypertension, dyslipidemia, or diabetes in a large
      clinical population. DESIGN: Retrospective cohort study within an 18-month period
      in 2002 to 2003. SETTING: Kaiser Permanente of Northern California. PATIENTS:
      253,238 adult members with poor control of 1 or more of these conditions.
      MEASUREMENTS: The authors assessed the proportion of patients with poor control
      who experienced a change in pharmacotherapy within 6 months, and they defined
      "appropriate care" as a therapy modification or return to control without therapy
      modification within 6 months. RESULTS: A total of 64% of patients experienced
      modifications in therapy for poorly controlled systolic blood pressure, 71% for
      poorly controlled diastolic blood pressure, 56% for poorly controlled low-density
      lipoprotein cholesterol level, and 66% for poorly controlled hemoglobin A1c
      level. Most frequent modifications were increases in number of drug classes (from
      70% to 84%) and increased dosage (from 15% to 40%). An additional 7% to 11% of
      those with poorly controlled blood pressure, but only 3% to 4% of those with
      elevated low-density lipoprotein cholesterol level or hemoglobin A1c level,
      returned to control without therapy modification. Patients with more than 1 of
      the 3 conditions, higher baseline values, and target organ damage were more
      likely to receive "appropriate care." LIMITATIONS: Patient preferences and
      suboptimal adherence to therapy were not measured and may explain some failures
      to act. CONCLUSIONS: As an additional measure of the quality of care, measuring
      therapy modifications in response to poor control in a large population is
      feasible. Many patients with poorly controlled hypertension, dyslipidemia, or
      diabetes had their therapy modified and, thus, seemed to receive clinically
      "appropriate care" with this new quality measure.

PMID- 16585662
TI  - Effects of comprehensive lifestyle modification on diet, weight, physical
      fitness, and blood pressure control: 18-month results of a randomized trial.
AB  - BACKGROUND: The main 6-month results from the PREMIER trial showed that
      comprehensive behavioral intervention programs improve lifestyle behaviors and
      lower blood pressure. OBJECTIVE: To compare the 18-month effects of 2
      multicomponent behavioral interventions versus advice only on hypertension
      status, lifestyle changes, and blood pressure. DESIGN: Multicenter, 3-arm,
      randomized trial conducted from January 2000 through November 2002. SETTING: 4
      clinical centers and a coordinating center. PATIENTS: 810 adult volunteers with
      prehypertension or stage 1 hypertension (systolic blood pressure, 120 to 159 mm
      Hg; diastolic blood pressure, 80 to 95 mm Hg). INTERVENTIONS: A multicomponent
      behavioral intervention that implemented long-established recommendations
      ("established"); a multicomponent behavioral intervention that implemented the
      established recommendations plus the Dietary Approaches to Stop Hypertension
      (DASH) diet ("established plus DASH"); and advice only. MEASUREMENTS: Lifestyle
      variables and blood pressure status. Follow-up for blood pressure measurement at
      18 months was 94%. RESULTS: Compared with advice only, both behavioral
      interventions statistically significantly reduced weight, fat intake, and sodium
      intake. The established plus DASH intervention also statistically significantly
      increased fruit, vegetable, dairy, fiber, and mineral intakes. Relative to the
      advice only group, the odds ratios for hypertension at 18 months were 0.83 (95%
      CI, 0.67 to 1.04) for the established group and 0.77 (CI, 0.62 to 0.97) for the
      established plus DASH group. Although reductions in absolute blood pressure at 18
      months were greater for participants in the established and the established plus
      DASH groups than for the advice only group, the differences were not
      statistically significant. LIMITATIONS: The exclusion criteria and the volunteer
      nature of this cohort may limit generalizability. Although blood pressure is a
      well-accepted risk factor for cardiovascular disease, the authors were not able
      to assess intervention effects on clinical cardiovascular events in this limited
      time and with this sample size. CONCLUSIONS: Over 18 months, persons with
      prehypertension and stage 1 hypertension can sustain multiple lifestyle
      modifications that improve control of blood pressure and could reduce the risk
      for chronic disease.

PMID- 16585664
TI  - Brief communication: sirolimus-associated pneumonitis: 24 cases in renal
      transplant recipients.
AB  - BACKGROUND: Interstitial pneumonitis is an ill-defined side effect of sirolimus,
      a new immunosuppressant drug recently introduced for patients having organ
      transplantation. OBJECTIVE: To evaluate clinical and laboratory features of
      sirolimus-associated pneumonitis. DESIGN: Case series. SETTING: 1 transplantation
      center in Paris, France. PATIENTS: 24 patients who had renal transplantation and
      developed sirolimus-associated pneumonitis, including 8 patients previously
      reported. MEASUREMENTS: Symptoms; laboratory tests, including bronchoalveolar
      fluid analysis; and computed tomography (CT) of the chest. INTERVENTION:
      Withdrawal or dose reduction of sirolimus. RESULTS: Clinical symptoms included
      cough (23 patients), fatigue (20 patients), fever (16 patients), and dyspnea (8
      patients). Computed tomography of the chest showed reticular and ground-glass
      opacities (4 patients), bronchiolitis obliterans-organizing pneumonia (19
      patients), and lobar consolidation (1 patient). Bronchoalveolar lavage showed
      lymphocytic (19 patients) or eosinophilic (3 patients) alveolitis or pulmonary
      hemorrhage (2 patients). A reduction in the sirolimus dose resulted in transient
      clinical improvement in 2 patients, but discontinuation of drug therapy was
      eventually necessary in all patients. All patients recovered completely within 6
      months. LIMITATIONS: The sirolimus trough level in patients from this single
      center was higher than that usually used in patients having renal
      transplantation. CONCLUSION: Lymphocytic alveolitis and radiologic bronchiolitis
      obliterans-organizing pneumonia are the key findings in sirolimus-associated
      pneumonitis. Sirolimus withdrawal was associated with recovery within 6 months.

PMID- 16585663
TI  - Outcomes of minor and subsyndromal depression among elderly patients in primary
      care settings.
AB  - BACKGROUND: Although depressive conditions in later life are a major public
      health problem, the outcomes of minor and subsyndromal depression are largely
      unknown. OBJECTIVE: To compare outcomes among patients with minor and
      subsyndromal depression, major depression, and no depression, and to examine
      putative outcome predictors. DESIGN: Cohort study. SETTING: Patients from primary
      care practices in greater New York City, and Philadelphia and Pittsburgh,
      Pennsylvania. PATIENTS: 622 patients who were at least 60 years of age and
      presented for treatment in primary care practices that provided usual care in a
      randomized, controlled trial of suicide prevention. Of the 441 (70.9%) patients
      who completed 1 year of follow-up, 122 had major depression, 205 had minor or
      subsyndromal depression, and 114 did not have depression at baseline.
      MEASUREMENTS: One year after a baseline evaluation, data were collected by using
      the following tools: Hamilton Depression Rating Scale, the depressive disorders
      section of the Structured Clinical Interview for DSM-IV (Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition), Charlson Comorbidity
      Index, Multilevel Assessment Instrument for measuring instrumental activities of
      daily living, Physical Component Summary of the Medical Outcomes Study Short Form
      36, and Duke Social Support Index. RESULTS: Patients with minor or subsyndromal
      depression had intermediate depressive and functional outcomes. Mean adjusted 1
      year Hamilton depression score was 10.9 (95% CI, 9.6 to 12.2) for those with
      initial major depression, 7.0 (CI, 5.9 to 8.1) for those with minor or
      subsyndromal depression, and 2.9 (CI, 1.6 to 4.2) for those without depression (P
      < 0.001 for each paired comparison). Compared with patients who were not
      depressed, those who had minor or subsyndromal depression had a 5.5-fold risk
      (CI, 3.1-fold to 10.0-fold) for major depression at 1 year after controlling for
      demographic characteristics (P < 0.001). Cerebrovascular risk factors were not
      associated with a diagnosis of depression at 1 year after controlling for overall
      medical burden. Initial medical burden, self-rated health, and subjective social
      support were significant independent predictors of depression outcome.
      LIMITATIONS: Participants received care at practices that had personnel who had
      been given enhanced education about depression treatment; 29.1% of participants
      withdrew from the study before completing 1 year of follow-up. CONCLUSIONS: The
      intermediate outcomes of minor and subsyndromal depression demonstrate the
      clinical significance of these conditions and suggest that they are part of a
      spectrum of depressive illness. Greater medical burden, poor subjective health
      status, and poorer subjective social support confer a higher risk for poor
      outcome.

PMID- 16585665
TI  - Computerization can create safety hazards: a bar-coding near miss.
AB  - Increasing numbers of hospitals are implementing bar-coding systems to prevent
      errors in patient identification. In the present case, a diabetic patient
      admitted to a teaching hospital was mistakenly given the bar-coded identification
      wristband of another patient who was admitted at the same time. When a laboratory
      result that documented the diabetic patient's severe hyperglycemia was entered
      into the other patient's electronic medical record, the latter patient seemed to
      have a very high glucose level and was almost given what could have been a fatal
      dose of insulin. This near miss shows that computer systems, although having the
      potential to improve safety, may create new kinds of errors if not accompanied by
      well-designed, well-implemented cross-check processes and a culture of safety.
      Moreover, computer systems may have the pernicious effect of weakening human
      vigilance, removing an important safety protection. Researchers should continue
      to study real-world implementation of computerized systems to understand their
      benefits and potential harms, and administrators and providers should seek ways
      to anticipate these harms and mitigate them.

PMID- 16585666
TI  - Adiposity of the heart, revisited.
AB  - Obesity is a major risk factor for heart disease. In the face of obesity's
      growing prevalence, it is important for physicians to be aware of emerging
      research of novel mechanisms through which adiposity adversely affects the heart.
      Conventional wisdom suggests that either hemodynamic (that is, increased cardiac
      output and hypertension) or metabolic (that is, dyslipidemic) derangements
      associated with obesity may predispose individuals to coronary artery disease and
      heart failure. The purpose of this review is to highlight a novel mechanism for
      heart disease in obesity whereby excessive lipid accumulation within the
      myocardium is directly cardiotoxic and causes left ventricular remodeling and
      dilated cardiomyopathy. Studies in animal models of obesity reveal that
      intracellular accumulation of triglyceride renders organs dysfunctional, which
      leads to several well-recognized clinical syndromes related to obesity (including
      type 2 diabetes). In these rodent models, excessive lipid accumulation in the
      myocardium causes left ventricular hypertrophy and nonischemic, dilated
      cardiomyopathy. Novel magnetic resonance spectroscopy techniques are now
      available to quantify intracellular lipid content in the myocardium and various
      other human tissues, which has made it possible to translate these studies into a
      clinical setting. By using this technology, we have recently begun to study the
      role of myocardial steatosis in the development of obesity-specific
      cardiomyopathy in humans. Recent studies in healthy individuals and patients with
      heart failure reveal that myocardial lipid content increases with the degree of
      adiposity and may contribute to the adverse structural and functional cardiac
      adaptations seen in obese persons. These studies parallel the observations in
      obese animals and provide evidence that myocardial lipid content may be a
      biomarker and putative therapeutic target for cardiac disease in obese patients.

PMID- 16585667
TI  - Improving the outcomes of metabolic conditions: managing momentum to overcome
      clinical inertia.

PMID- 16585668
TI  - Minor depression: midway between major depression and euthymia.

PMID- 16585669
TI  - The pediatric arrest.

PMID- 16585670
TI  - Efficacy and safety of inhaled insulin therapy.

PMID- 16585671
TI  - Efficacy and safety of inhaled insulin therapy.

PMID- 16585673
TI  - Evidence for vascular spread of varicella zoster-associated vasculopathy.

PMID- 16585672
TI  - Survivor costs in cost-effectiveness analysis.

PMID- 16585675
TI  - Notification that new names and new combinations have appeared in volume 56, part
      1, 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- 16585674
TI  - Reconstitution of hematin for intravenous infusion.

PMID- 16585676
TI  - Desulfovibrio frigidus sp. nov. and Desulfovibrio ferrireducens sp. nov.,
      psychrotolerant bacteria isolated from Arctic fjord sediments (Svalbard) with the
      ability to reduce Fe(III).
AB  - Strains 18T, 61T and 77 were isolated from two permanently cold fjord sediments
      on the west coast of Svalbard. The three psychrotolerant strains, with
      temperature optima at 20-23 degrees C, were able to grow at the freezing point of
      sea water, -2 degrees C. The strains oxidized important fermentation products
      such as hydrogen, formate and lactate with sulfate as the electron acceptor.
      Sulfate could be replaced by sulfite, thiosulfate or elemental sulfur. Poorly
      crystalline and soluble Fe(III) compounds were reduced in sulfate-free medium,
      but no growth occurred under these conditions. In the absence of electron
      acceptors, fermentative growth was possible. The pH optimum for the strains was
      around 7.1. The DNA G+C contents were 43.3 and 42.0 mol% for strains 18T and 61T,
      respectively. Strains 18T, 61T and 77 were most closely related to Desulfovibrio
      hydrothermalis (95.0-95.7 % 16S rRNA gene sequence similarity). Strains 18T and
      77, exhibiting 99.9 % sequence similarity, represent a novel species for which
      the name Desulfovibrio frigidus sp. nov. is proposed. The type strain is strain
      18T (=DSM 17176T = JCM 12924T). Strain 61T was closely related to strains 18T and
      77 (97.6 and 97.5 % 16S rRNA gene sequence similarity), but on the basis of DNA
      DNA hybridization strain 61T represents a novel species for which the name
      Desulfovibrio ferrireducens sp. nov. is proposed. The type strain is strain 61T
      (=DSM 16995T = JCM 12925T).

PMID- 16585677
TI  - Desulfotomaculum arcticum sp. nov., a novel spore-forming, moderately
      thermophilic, sulfate-reducing bacterium isolated from a permanently cold fjord
      sediment of Svalbard.
AB  - Strain 15T is a novel spore-forming, sulfate-reducing bacterium isolated from a
      permanently cold fjord sediment of Svalbard. Sulfate could be replaced by sulfite
      or thiosulfate. Hydrogen, formate, lactate, propionate, butyrate, hexanoate,
      methanol, ethanol, propanol, butanol, pyruvate, malate, succinate, fumarate,
      proline, alanine and glycine were used as electron donors in the presence of
      sulfate. Growth occurred with pyruvate as sole substrate. Optimal growth was
      observed at pH 7.1-7.5 and concentrations of 1-1.5 % NaCl and 0.4 % MgCl2. Strain
      15T grew between 26 and 46.5 degrees C and optimal growth occurred at 44 degrees
      C. Therefore, strain 15T apparently cannot grow at in situ temperatures of Arctic
      sediments from where it was isolated, and it was proposed that it was present in
      the sediment in the form of spores. The DNA G+C content was 48.9 mol%. Strain 15T
      was most closely related to Desulfotomaculum thermosapovorans MLF(T) (93.5 % 16S
      rRNA gene sequence similarity). Strain 15T represents a novel species, for which
      the name Desulfotomaculum arcticum sp. nov. is proposed. The type strain is
      strain 15T (=DSM 17038T = JCM 12923T).

PMID- 16585678
TI  - Clostridium ganghwense sp. nov., isolated from tidal flat sediment.
AB  - A Gram-negative, strictly anaerobic, halophilic, motile, sporulating and rod
      shaped bacterium, designated strain HY-42-06T, was isolated from tidal flat
      sediment from Ganghwa Island in South Korea. The isolate produced glycerol,
      ethanol and CO2 as fermentation end-products from glucose. Strain HY-42-06T grew
      optimally at 35 degrees C, pH 7.5 and 3 % (w/v) artificial sea salts. No growth
      was observed in the absence of sea salts. In phylogenetic analyses based on 16S
      rRNA gene sequence, strain HY-42-06T showed a distinct phyletic line within the
      members of cluster I of the order Clostridiales. The closest phylogenetic
      neighbour to strain HY-42-06T was Clostridium novyi ATCC 17861T (94.91 % 16S rRNA
      gene sequence similarity). Several phenotypic characters readily differentiate
      the tidal flat isolate from phylogenetically related clostridia. On the basis of
      polyphasic evidence, strain HY-42-06T should be classified as a representative of
      a novel species, for which the name Clostridium ganghwense sp. nov. is proposed.
      The type strain is HY-42-06T (=IMSNU 40127T = KCTC 5146T = JCM 13193T).

PMID- 16585679
TI  - Megasphaera paucivorans sp. nov., Megasphaera sueciensis sp. nov. and Pectinatus
      haikarae sp. nov., isolated from brewery samples, and emended description of the
      genus Pectinatus.
AB  - Seven unidentified strictly anaerobic, Gram-negative, non-spore-forming bacteria
      from spoiled beer or the brewery environment were characterized. Based on 16S
      rRNA gene sequence analyses, all strains were affiliated to the Sporomusa sub
      branch of the class 'Clostridia'. Three of the strains were non-motile cocci, on
      average 1.5 x 1.2 microm or 1.2 x 1.0 microm, occurring mainly singly or in
      pairs. They shared nearly identical (>99 %) 16S rRNA gene sequences, being most
      closely related to the species of the Megasphaera-Anaeroglobus group (< or =93.9
      % similarity). According to DNA-DNA hybridization results, the coccoid strains
      represented two genospecies, neither of which was related to any of the
      recognized Megasphaera species. Several phenotypic characteristics and/or DNA G+C
      content also differentiated the strains from each other and from their closest
      relatives. The other four novel strains were motile, slightly curved to helical
      rods, 0.6-0.8 x 3-50 microm or more in size. They shared identical 16S rRNA gene
      sequences and ribofragment patterns. The highest 16S rRNA gene similarity was
      found between these isolates and Pectinatus cerevisiiphilus ATCC 29359T (95.6 %)
      and Pectinatus frisingensis ATCC 33332T (93.6 %). The novel strains also differed
      from recognized Pectinatus species in their sugar utilization, proteolytic
      activity, catalase activity, antibiotic resistance and temperature tolerance. The
      results suggest that the bacteria belong to three novel species, for which the
      names Megasphaera paucivorans sp. nov. (type strain VTT E-032341T = DSM 16981T),
      Megasphaera sueciensis sp. nov. (type strain VTT E-97791T = DSM 17042T) and
      Pectinatus haikarae sp. nov. (type strain VTT E-88329T = DSM 16980T) are
      proposed.

PMID- 16585681
TI  - Pseudomonas otitidis sp. nov., isolated from patients with otic infections.
AB  - A novel Pseudomonas species, for which the name Pseudomonas otitidis sp. nov. is
      proposed, was identified from clinical specimens of infected human ears. Forty
      one pseudomonads (34 from patients with acute otitis externa, six from patients
      with acute otitis media with otorrhoea and one from a patient with chronic
      suppurative otitis media) were recovered that did not match any known species. On
      the basis of genetic analyses and biochemical characterization, these isolates
      were shown to belong to the genus Pseudomonas. 16S rRNA gene sequence analysis
      and DNA-DNA hybridization studies indicated that this novel bacterium is closely
      related to, but different from, Pseudomonas aeruginosa. A description of this
      species is based on polyphasic studies of 11 clinical isolates. The type strain
      of Pseudomonas otitidis is MCC10330T (=ATCC BAA-1130T = DSM 17224T).

PMID- 16585680
TI  - Sphingomonas soli sp. nov., a beta-glucosidase-producing bacterium in the family
      Sphingomonadaceae in the alpha-4 subgroup of the Proteobacteria.
AB  - Strain T5-04T, a Gram-negative, non-spore-forming, rod-shaped bacterium, was
      isolated from soil of a ginseng field in South Korea and characterized in order
      to determine its taxonomic position. 16S rRNA gene sequence analysis revealed
      that strain T5-04T belongs to the alpha-4 subgroup of the Proteobacteria, and the
      highest degrees of sequence similarity determined were to Sphingomonas
      asaccharolytica IFO 10564T (97.5 %), Sphingomonas koreensis JSS26T (97.1 %),
      Sphingomonas mali IFO 15500T (96.7 %) and Sphingomonas pruni IFO 15498(T) (96.6
      %). Chemotaxonomic data revealed that strain T5-04T possesses ubiquinone Q-10
      predominantly, C(18 : 1) as the predominant fatty acid and sphingoglycolipids,
      all of which corroborate its assignment to the genus Sphingomonas. The results of
      DNA-DNA hybridization and physiological and biochemical tests clearly
      demonstrated that strain T5-04T represents a distinct species. Based on
      polyphasic evidence, T5-04T (=KCTC 12210T = NBRC 100801T = IAM 15213T) should be
      classified as the type strain of a novel Sphingomonas species, for which the name
      Sphingomonas soli sp. nov. is proposed.

PMID- 16585682
TI  - Clostridium schirmacherense sp. nov., an obligately anaerobic, proteolytic,
      psychrophilic bacterium isolated from lake sediment of Schirmacher Oasis,
      Antarctica.
AB  - A novel obligately anaerobic, proteolytic bacterium, designated AP15T, was
      isolated from lake sediments of Schirmacher Oasis, Antarctica. The bacterium
      produced maximum cell mass between 5 and 10 degrees C in an anaerobic basal
      medium containing 0.5 % tryptone and peptone. The strain grew optimally at a pH
      around 8.0 and tolerated NaCl up to a concentration of 7.5 %. It contained
      diphosphatidylglycerol as the major phospholipid and C(15 : 0), C(16 : 0) and
      C(17 : 0) as the major cellular fatty acids. Several amino acids, including
      arginine, leucine, isoleucine, cysteine, glutamate and serine, supported growth.
      Glutamate was degraded to acetate, propionate, CO2 and H2. In addition, the
      strain degraded carbohydrates including glucose, raffinose, adonitol, ribose and
      rhamnose. The main fermentation products during growth on glucose were H2, CO2,
      formate, acetate, propionate and isovalerate. The DNA G+C content of the
      bacterium was 24 mol%. On the basis of a phylogenetic analysis, strain AP15(T) is
      identified as a close relative of Clostridium subterminale ATCC 25774T, with
      which it shares 99.5 % similarity at the 16S rRNA gene sequence level; however,
      it exhibits a low DNA-DNA binding value (55 %) to this strain at the whole-genome
      level. In addition to showing other major differences with respect to C.
      subterminale and other members of the genus Clostridium, AP15T also exhibits
      phenotypic differences. On the basis of these differences, strain AP15T is
      identified as representing a novel species of the genus Clostridium, for which
      the name Clostridium schirmacherense sp. nov. is proposed. The type strain is
      AP15T (=DSM 17394T = JCM 13289T).

PMID- 16585683
TI  - Sporacetigenium mesophilum gen. nov., sp. nov., isolated from an anaerobic
      digester treating municipal solid waste and sewage.
AB  - Two mesophilic, anaerobic bacterial strains (ZLJ115T and L4-2) were isolated from
      the sludge of an anaerobic digester treating municipal solid waste and sewage in
      Fujian province, China. The strains were Gram-positive, spore-forming, motile
      rods (0.9-1.0 x 3.6-7.3 microm). Growth of the strains was observed at 20-42
      degrees C and pH 6.0-9.5. Both strains fermented several mono- and disaccharides.
      The main fermentation products from glucose were acetate, ethanol, hydrogen and
      carbon dioxide. Optimal hydrogen production by the new isolates was observed at
      pH 8.8 and 39 degrees C, and 1.4 mol H2 was detected from fermentation of 1 mol
      glucose. The DNA G+C contents of strains ZLJ115T and L4-2 were 53.9 and 54.3
      mol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences
      revealed that the isolates represented a novel phyletic sublineage within cluster
      XI of the clostridia, clustering with four thermophilic species, with <93.8 % 16S
      rRNA gene sequence similarity to previously described species. Phenotypically,
      the new isolates were distinguished from their phylogenetic relatives by growing
      mesophilically and by fermenting a variety of pentoses, as well as their higher
      genome DNA G+C content. On the basis of polyphasic evidence from this study, a
      novel genus and species are proposed, Sporacetigenium mesophilum gen. nov., sp.
      nov.; strain ZLJ115T (=DSM 16796T = AS 1.5019T) is the type strain of
      Sporacetigenium mesophilum.

PMID- 16585684
TI  - Yeosuana aromativorans gen. nov., sp. nov., a mesophilic marine bacterium
      belonging to the family Flavobacteriaceae, isolated from estuarine sediment of
      the South Sea, Korea.
AB  - A marine bacterium, GW1-1T, capable of degrading benzo[a]pyrene (BaP), was
      isolated from estuarine sediments of the South Sea (the Korea Strait), Korea,
      after an enrichment culture maintained for 2 years in a medium supplemented with
      a mixture of BaP and pyrene. The strain formed yellowish-brown colonies on marine
      agar 2216. Cells were strictly aerobic, non-motile, Gram-negative rods and
      produced non-diffusible carotenoid pigments. Optimal growth occurred in the
      presence of 1 % (w/v) NaCl and at pH 7 and 33-36 degrees C. No growth occurred
      without supplementation with either CaCl2 or MgCl2, even in the presence of NaCl.
      Phylogenetic analysis based on the nearly complete sequence of the 16S rRNA gene
      revealed that the isolate formed a phyletic lineage with the genera Gelidibacter
      (93.9-94.7 % gene sequence similarity), Subsaximicrobium (93.3 %) and
      Subsaxibacter (93.9 %). The isolate also showed high sequence similarities to
      Gaetbulibacter saemankumensis (94.5 %), Algibacter lectus (94.2 %), members of
      the genus Bizionia (93.6-94.3 %) and Formosa algae (93.2 %), even though it
      belonged to a different phyletic line. The major respiratory quinones of the
      isolate were menaquinones MK-5 and MK-6. The DNA G+C content was 51.4 mol%.
      Dominant fatty acids were i-15 : 0, a-15 : 0, i-15 : 1omega10c and 16 : 1. On the
      basis of this polyphasic taxonomic evidence, strain GW1-1T is classified as a
      member of a novel genus and species in the family Flavobacteriaceae, for which
      the name Yeosuana aromativorans gen. nov., sp. nov. is proposed. The type strain
      of the type species is GW1-1T (=KCCM 42019T = JCM 12862T).

PMID- 16585685
TI  - Kocuria aegyptia sp. nov., a novel actinobacterium isolated from a saline,
      alkaline desert soil in Egypt.
AB  - A coccoid, non-motile actinobacterium, designated strain YIM 70003T, was isolated
      from a saline, alkaline, desert-soil sample from Egypt. Phylogenetic analysis
      based on 16S rRNA gene sequences revealed that the organism formed a distinct
      phyletic line within the genus Kocuria and was most closely related to Kocuria
      polaris DSM 14382T (98.6 % sequence similarity) and Kocuria rosea DSM 20447T
      (98.2 %). Chemotaxonomic data, including the Lys-Ala3 peptidoglycan type, the
      presence of phosphatidylglycerol and diphosphatidylglycerol as the predominant
      phospholipids, the presence of MK-8(H2) and MK-9(H2) as the major menaquinones,
      the predominance of fatty acids ai-C(15 : 0) and i-C(15 : 0) and the DNA G+C
      content, also supported the affiliation of the isolate to the genus Kocuria. The
      low DNA-DNA relatedness with K. polaris DSM 14382T (56.6 %) and K. rosea DSM
      20447T (15.5 %) in combination with phenotypic data show that strain YIM 70003T
      should be classified as a novel species of the genus Kocuria. The name Kocuria
      aegyptia sp. nov. is proposed, with strain YIM 70003T (=CCTCC AA203006T = CIP
      107966T = KCTC 19010T = DSM 17006T) as the type strain.

PMID- 16585687
TI  - Photobacterium ganghwense sp. nov., a halophilic bacterium isolated from sea
      water.
AB  - A marine bacterial strain, designated FR1311T, was isolated from a sea-water
      sample from Ganghwa Island, South Korea. Cells were Gram-negative, facultatively
      anaerobic, catalase- and oxidase-positive, motile, oval or rod-shaped and
      halophilic (optimum sea-salt concentration for growth of 5-6 %). Phylogenetic
      analysis of its 16S rRNA gene sequence revealed that it represented a distinct
      line of descent within the genus Photobacterium. The major fatty acids were
      straight-chain saturated (C(16 : 0)) and monounsaturated fatty acids (C(16 :
      1)omega7c and C(18 : 1)omega7c). The predominant respiratory lipoquinone was Q-8.
      The DNA G+C content was 44 mol%. The phenotypic features of strain FR1199T were
      similar to those of Photobacterium damselae subsp. damselae and Photobacterium
      damselae subsp. piscicida, but several physiological and chemotaxonomic
      properties readily distinguish the new isolate from them. On the basis of the
      polyphasic results revealed in this study, FR1311T is considered to be the type
      strain of a novel species, for which the name Photobacterium ganghwense sp. nov.
      is proposed. The type strain is FR1311T (=IMSNU 60287T = KCTC 12328T = JCM
      12487T).

PMID- 16585686
TI  - Millisia brevis gen. nov., sp. nov., an actinomycete isolated from activated
      sludge foam.
AB  - The taxonomic position of two mycolic-acid-producing actinomycetes, isolates J81T
      and J82, which were recovered from activated sludge foam, was clarified.
      Comparative 16S rRNA gene sequence studies indicated that the organisms formed a
      distinct lineage within the Corynebacterineae 16S rRNA gene tree. The taxonomic
      integrity of this group was underpinned by a wealth of phenotypic data, notably
      characteristic rudimentary right-angled branching. In addition, isolate J81T
      contained the following: meso-diaminopimelic acid, arabinose and galactose; N
      glycolated muramic acid residues; a dihydrogenated menaquinone with eight
      isoprene units as the predominant isoprenologue; a fatty acid profile rich in
      oleic and palmitoleic acids and with relatively small proportions of myristic,
      stearic and tuberculostearic acids; mycolic acids with 44-52 carbons; and
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol,
      phosphatidylinositol and phosphatidylinositol mannosides as major polar lipids.
      Strain J81T was found to have a chemotaxonomic profile that serves to distinguish
      it from representatives of all of the other taxa classified as belonging to the
      suborder Corynebacterineae. In the light of these data, it is proposed that the
      two isolates be classified in a novel monospecific genus. The name proposed for
      this taxon is Millisia brevis gen. nov., sp. nov.; strain J81T (=DSM 44463T =
      NRRL B-24424T) is the type strain of Millisia brevis.

PMID- 16585688
TI  - Peptostreptococcus stomatis sp. nov., isolated from the human oral cavity.
AB  - Seven strains of anaerobic Gram-positive cocci isolated from human oral sites
      were subjected to a comprehensive range of phenotypic and genotypic tests. 16S
      rRNA gene sequence analysis revealed that the strains constituted a homogeneous
      group that was distinct from species with validly published names, but related to
      Peptostreptococcus anaerobius. All oral strains tested belonged to this group,
      whereas all non-oral strains studied were confirmed as P. anaerobius. A novel
      species, Peptostreptococcus stomatis sp. nov., is proposed to accommodate these
      oral strains. P. stomatis is weakly saccharolytic and produces acetic, butyric,
      isobutyric, isovaleric and isocaproic acids as end products of fermentation. The
      type strain of P. stomatis is W2278T (=DSM 17678T = CCUG 51858T); the G+C content
      of the DNA of this strain is 36 mol%.

PMID- 16585689
TI  - Ethanoligenens harbinense gen. nov., sp. nov., isolated from molasses wastewater.
AB  - Two strictly anaerobic bacterial strains (YUAN-3T and X-29) were isolated from
      anaerobic activated sludge of molasses wastewater in a continuous stirred-tank
      reactor. The strains were Gram-positive, non-spore-forming, mesophilic and
      motile. Cells were regular rods (0.4-0.8 x 1.5-8.0 microm) and occurred singly,
      in pairs and sometimes in chains of up to eight. Autoaggregative and
      autofluorescent growth of strain YUAN-3T and non-aggregative growth of strain X
      29 were observed at 20-44 degrees C and pH 3.5-9.0. Both strains hydrolysed
      gelatin and aesculin and fermented several kinds of mono-, di- and
      oligosaccharides. Fermentation end products formed from glucose were acetate,
      ethanol, hydrogen and carbon dioxide. The predominant cellular fatty acids were
      the branched-chain fatty acids iso-C(16 : 0) (44.18 %) and iso-C(12 : 0) (26.67
      %). The DNA G+C contents of strains YUAN-3T and X-29 were 47.8 and 49.0 mol%,
      respectively. Phylogenetic analysis based on 16S rRNA gene sequences revealed
      that the isolates represent a novel phyletic sublineage within the Clostridium
      cellulosi rRNA cluster, with <92 % 16S rRNA gene sequence similarity to currently
      known species. On the basis of polyphasic evidence from this study, it is
      proposed that the unknown bacterium should be classified in a new genus as a
      novel species, Ethanoligenens harbinense gen. nov., sp. nov. The type strain of
      Ethanoligenens harbinense is YUAN-3T (=JCM 12961T = CGMCC 1.5033T).

PMID- 16585691
TI  - Halovivax asiaticus gen. nov., sp. nov., a novel extremely halophilic archaeon
      isolated from Inner Mongolia, China.
AB  - Strain EJ-46T, a novel pleomorphic, aerobic, extremely halophilic member of the
      Archaea was isolated from sediment of the saline Lake Ejinor, in Inner Mongolia,
      China. This organism was neutrophilic and required at least 15 % (2.5 M) NaCl for
      growth. MgCl2 was not required. The isolate was able to grow at pH 6.0-9.0.
      Optimum growth occurred in media containing 20 % (3.4 M) NaCl at pH 7.0-7.5.
      Polar lipid analysis revealed the presence of phosphatidylglycerol and
      phosphatidylglycerol phosphate methyl ester, derived from both C20C20 and C20C25
      glycerol diethers. Four glycolipids were detected, one of which may be novel. The
      DNA G+C content was 60.3 mol%. 16S rRNA gene analysis revealed that strain EJ-46T
      was a member of the phylogenetic group defined by the family Halobacteriaceae,
      and the highest 16S rRNA gene similarity values of 94.9 and 94.8 % were obtained
      with the haloalkaliphilic species of the genus Natronococcus, Natronococcus
      occultus and Natronococcus amylolyticus, respectively. Based on the phenotypic,
      genotypic and phylogenetic analyses, it is proposed that the novel isolate should
      be classified as representing a new genus and species, for which the name
      Halovivax asiaticus gen. nov., sp. nov. is proposed. The type strain is EJ-46T
      (=CGMCC 1.4248T = CECT 7098T).

PMID- 16585690
TI  - Mycoplasma iguanae sp. nov., from a green iguana (Iguana iguana) with vertebral
      disease.
AB  - Strain 2327T, first cultured from vertebral abscesses of green iguanas (Iguana
      iguana) collected in Florida, USA, was readily distinguished from all previously
      described mollicutes by 16S rRNA gene sequence comparisons. Strain 2327T lacks a
      cell wall, ferments glucose, does not hydrolyse arginine, aesculin or urea and is
      sensitive to digitonin. Western blots distinguished the novel isolate
      serologically from the most closely related members of the Mycoplasma
      neurolyticum cluster. On the basis of these data, the isolate represents a novel
      species for which the name Mycoplasma iguanae sp. nov. is proposed. The type
      strain is strain 2327T (=ATCC BAA-1050T = NCTC 11745T).

PMID- 16585692
TI  - Lutibacter litoralis gen. nov., sp. nov., a marine bacterium of the family
      Flavobacteriaceae isolated from tidal flat sediment.
AB  - A rod-shaped marine bacterium, designated strain CL-TF09T, isolated from a tidal
      flat in Ganghwa, Korea, was characterized based on its physiological and
      biochemical features, fatty acid profile and phylogenetic position. 16S rRNA gene
      sequence analysis revealed a clear affiliation with the family Flavobacteriaceae.
      Strain CL-TF09T showed the closest phylogenetic relationship with the genera
      Tenacibaculum and Polaribacter; sequence similarities between CL-TF09T and the
      type strains of Tenacibaculum and Polaribacter species ranged from 90.7 to 91.8
      %. Cells of strain CL-TF09T were non-motile and grew on solid media as yellow
      colonies. The strain grew in the presence of 1-5 % sea salts, within a
      temperature range of 5-30 degrees C and at pH 7-8. The strain had iso-C(15 : 0) 3
      OH (17.4 %), iso-C(15 : 0) (16.7 %), anteiso-C(15 : 0) (15.1 %) and iso-C(16 : 0)
      3-OH (13.4 %) as predominant fatty acids. The DNA G+C content was 33.9 mol%.
      Based on the physiological, fatty acid composition and phylogenetic data
      presented, strain CL-TF09T is considered to represent a novel genus and species
      of the family Flavobacteriaceae, for which the name Lutibacter litoralis gen.
      nov., sp. nov. is proposed. The type strain is CL-TF09T (=KCCM 42118T = JCM
      13034T).

PMID- 16585693
TI  - Algoriphagus terrigena sp. nov., isolated from soil.
AB  - A Gram-negative, non-motile, non-spore-forming bacterial strain, DS-44T, was
      isolated from soil from Dokdo in Korea, and its taxonomic position was
      investigated by using a polyphasic approach. It grew optimally at 25 degrees C
      and in the presence of 2 % (w/v) NaCl. Strain DS-44T contained MK-7 as the
      predominant menaquinone and iso-C(15 : 0) and C(16 : 1)omega7c and/or iso-C(15 :
      0) 2-OH as the major fatty acids. The DNA G+C content was 49.0 mol%. Phylogenetic
      analyses based on 16S rRNA gene sequences revealed that strain DS-44T belongs to
      the genus Algoriphagus of the phylum Bacteroidetes. Similarity values between the
      16S rRNA gene sequences of strain DS-44T and those of the type strains of
      recognized Algoriphagus species were in the range 93.8-95.7 %, making it possible
      to categorize strain DS-44T as a species that is separate from previously
      described Algoriphagus species. On the basis of its phenotypic properties and
      phylogenetic distinctiveness, strain DS-44T (=KCTC 12545T = CIP 108837T) was
      classified in the genus Algoriphagus as the type strain of a novel species, for
      which the name Algoriphagus terrigena sp. nov. is proposed.

PMID- 16585694
TI  - Cohnella thermotolerans gen. nov., sp. nov., and classification of 'Paenibacillus
      hongkongensis' as Cohnella hongkongensis sp. nov.
AB  - A Gram-positive, rod-shaped, endospore-forming organism, strain CCUG 47242T, was
      isolated from a sample of industrial starch production in Sweden. 16S rRNA gene
      sequence analysis demonstrated that this isolate was moderately related to
      species of the genus Paenibacillus, with <94.4 % sequence similarity to all other
      hitherto described Paenibacillus species. Strain CCUG 47242T showed the greatest
      sequence similarity (96.5 %) to 'Paenibacillus hongkongensis' HKU3, a strain with
      a name that has not yet been validly published. Chemotaxonomic data [major
      menaquinone, MK-7 (98 %); major polar lipids, diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine, lysyl-phosphatidylglycerol, two
      unknown phospholipids, four unknown aminophospholipids; major fatty acids, iso
      C16 : 0 and anteiso-C15 : 0] showed some significant differences when compared
      with the type species of the genus Paenibacillus, Paenibacillus polymyxa.
      Physiological and biochemical tests allowed clear phenotypic differentiation of
      strain CCUG 47242T from strain HKU3. On the basis of 16S rRNA gene sequence
      analysis, in combination with chemotaxonomic data, strains CCUG 47242T and HKU3
      represent two novel species of a new genus of endospore-forming bacteria for
      which we propose the names Cohnella thermotolerans gen. nov., sp. nov. (type
      strain CCUG 47242T = CIP 108492T = DSM 17683T) and Cohnella hongkongensis sp.
      nov. (type strain HKU3T = CCUG 49571T = CIP 107898T = DSM 17642T).

PMID- 16585695
TI  - Deinococcus ficus sp. nov., isolated from the rhizosphere of Ficus religiosa L.
AB  - A pale-pink strain (CC-FR2-10T) from the rhizosphere of the sacred tree Ficus
      religiosa L. in Taiwan was investigated by using a polyphasic taxonomic approach.
      The cells were Gram-positive, rod-shaped and non-spore-forming. Phylogenetic
      analyses using the 16S rRNA gene sequence of the isolate indicated that the
      organism belongs to the genus Deinococcus, the highest sequence similarities
      being found with Deinococcus grandis (96.1 %), Deinococcus radiodurans (94.3 %),
      Deinococcus radiopugnans (93.2 %), Deinococcus indicus (93.0 %), Deinococcus
      proteolyticus (92.5 %), Deinococcus murrayi (92.4 %) and Deinococcus geothermalis
      (90.7 %). The DNA-DNA relatedness with respect to D. grandis DSM 3963T was 17.9
      %. Chemotaxonomic data revealed that strain CC-FR2-10T contains only menaquinone
      MK-8 as the respiratory quinone, unknown phosphoglycolipids as the predominant
      polar lipids and 16 : 1omega7c, 17 : 1omega8c and 17 : 1omega9c iso as the
      predominant fatty acids. The biochemical and chemotaxonomic properties
      demonstrate that strain CC-FR2-10T represents a novel species, for which the name
      Deinococcus ficus sp. nov. is proposed. The type strain is CC-FR2-10T (=CCUG
      51391T [corrected] = CIP 108832T).

PMID- 16585696
TI  - Reclassification of Lactobacillus thermotolerans Niamsup et al. 2003 as a later
      synonym of Lactobacillus ingluviei Baele et al. 2003.
AB  - The relatedness of the species Lactobacillus ingluviei and Lactobacillus
      thermotolerans was investigated by comparing partial sequences of the 16S rRNA
      gene (99.9 % similarity over 1504 bp), the hsp60 gene (98.8 % similarity over 954
      bp) and the recA gene (98.5 % similarity over 452 bp) and by determining DNA-DNA
      binding levels (79+/-3 %) and genomic DNA G+C contents (50 and 49 mol%,
      respectively). These data, in addition to their similar biochemical
      characteristics, suggest that the two taxa constitute a single species. According
      to Rules 38 and 42 of the Bacteriological Code, they should be united under the
      name Lactobacillus ingluviei, with the name Lactobacillus thermotolerans as a
      later heterotypic synonym.

PMID- 16585697
TI  - Carboxydocella sporoproducens sp. nov., a novel anaerobic CO-utilizing/H2
      producing thermophilic bacterium from a Kamchatka hot spring.
AB  - A novel anaerobic, thermophilic, CO-utilizing bacterium, strain KarT, was
      isolated from a hot spring of Karymskoe Lake, Kamchatka Peninsula. The cells of
      the novel isolate were Gram-positive, spore-forming, short rods. The bacterium
      grew chemolithoautotrophically on CO, producing equimolar quantities of H2 and
      CO2 (according to the equation CO + H2O --> CO2 + H2), and in the absence of CO,
      under N2 in the gas phase, chemoorganoheterotrophically with yeast extract,
      sucrose or pyruvate. Growth was observed in the temperature range 50-70 degrees
      C, with an optimum at 60 degrees C, and in the pH range 6.2-8.0, with an optimum
      at pH 6.8. The micro-organism did not grow on solid media; it was able to grow
      only in semi-solid medium containing 0.5 % agar. The generation time under
      optimal conditions for chemolithoautotrophic growth was 1 h. The G+C content of
      the DNA was 46.5+/-1 mol%. Growth was completely inhibited by penicillin,
      novobiocin, streptomycin, kanamycin and neomycin. Analysis of the 16S rRNA gene
      sequence showed that the isolate should be assigned to the genus Carboxydocella.
      On the basis of the results of DNA-DNA hybridization and morphological and
      physiological analyses, strain KarT represents a novel species of the genus
      Carboxydocella, for which the name Carboxydocella sporoproducens sp. nov. is
      proposed. The type strain is KarT (=DSM 16521T = VKM B-2358T).

PMID- 16585698
TI  - Characterization of clinical isolates previously identified as Oerskovia turbata:
      proposal of Cellulosimicrobium funkei sp. nov. and emended description of the
      genus Cellulosimicrobium.
AB  - Taxonomic studies were performed on 13 clinical isolates (ten of which were
      epidemiologically related) that had been previously identified as Oerskovia
      turbata. Comparative phylogenetic analysis, based on 16S rRNA gene sequences,
      indicated that the isolates are closely related to Cellulosimicrobium cellulans
      with sequence similarity values ranging from 99.5 to 99.8 %. Chemotaxonomic
      results (fatty acid profiles and menaquinones) supported the inclusion of these
      isolates in the genus Cellulosimicrobium. The DNA G+C content was 74.5 mol%. The
      results of DNA-DNA reassociation, whole-cell sugars (with galactose as the
      characteristic whole sugar) and phenotypic properties, including antimicrobial
      resistance, indicated that these isolates are representatives of a novel species
      of the genus Cellulosimicrobium. The name Cellulosimicrobium funkei sp. nov. is
      proposed for the novel strains, with strain W6122T (=ATCC BAA-886T = DSM 16025T =
      CCUG 50705T) as the type strain. The definition of this novel Cellulosimicrobium
      species will assist in the understanding of the epidemiology and clinical
      significance of these micro-organisms.

PMID- 16585699
TI  - Oceanobacillus oncorhynchi subsp. incaldanensis subsp. nov., an alkalitolerant
      halophile isolated from an algal mat collected from a sulfurous spring in
      Campania (Italy), and emended description of Oceanobacillus oncorhynchi.
AB  - A halophilic, alkalitolerant bacterium, strain 20AGT, was isolated from an algal
      mat collected from a sulfurous spring located in Santa Maria Incaldana
      (Mondragone, Campania Region, southern Italy). The isolate is Gram-positive,
      ferments several carbohydrates and has motile, rod-shaped cells that do not
      sporulate. The isolate grows at pH 6.5-9.5 and in 5-20 % NaCl. On the basis of
      16S rRNA gene sequence similarity, the strain was shown to belong to the genus
      Oceanobacillus; strain 20AGT showed 96.6 % 16S rRNA gene sequence similarity to
      the type strain of Oceanobacillus iheyensis, DSM 14371T, and 99.5 % similarity to
      Oceanobacillus oncorhynchi NCIMB 14022T. Levels of DNA-DNA relatedness between
      strain 20AGT and O. iheyensis DSM 14371T and O. oncorhynchi NCIMB 14022T were
      respectively 29.4 and 59.0 %. The G+C content of the DNA of strain 20AGT was 40.1
      mol%. The predominant respiratory quinone was MK-7, phosphatidylglycerol and
      phosphatidylcholine were the predominant polar lipids and minor phospholipids
      were also detected. ai-C14 : 0, ai-C15 : 0 and i-C15 : 0 were the major fatty
      acids. Strain 20AGT accumulated osmolytes and produced exopolysaccharide. On the
      basis of phenotypic characteristics, phylogenetic data and DNA-DNA relatedness
      data, isolate 20AGT should be designated as the type strain of a subspecies of
      Oceanobacillus oncorhynchi, for which the name Oceanobacillus oncorhynchi subsp
      incaldanensis subsp. nov. is proposed. The type strain is 20AGT (=DSM 16557T =
      ATCC BAA-954T).

PMID- 16585700
TI  - Variovorax dokdonensis sp. nov., isolated from soil.
AB  - A Gram-negative, motile and oval- or rod-shaped bacterial strain, DS-43T, was
      isolated from soil from Dokdo, Korea, and its taxonomic position was investigated
      by using a polyphasic approach. The strain grew optimally at pH 7.0-8.0 and at 30
      degrees C in the presence of 0.5 % (w/v) NaCl. Strain DS-43T had Q-8 as the
      predominant ubiquinone and C(16 : 0), C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH,
      C(18 : 1)omega7c and C(17 : 0) cyclo as the major fatty acids, which are
      consistent with the corresponding data for the type strain (KCTC 12459T) of
      Variovorax paradoxus. The DNA G+C content was 66.0 mol%. Phylogenetic analyses
      based on 16S rRNA gene sequences showed that strain DS-43T was most closely
      related to Variovorax paradoxus, the only recognized species of the genus. The
      level of 16S rRNA gene sequence similarity between strain DS-43T and V. paradoxus
      IAM 12373T was 97.3 %. DNA-DNA relatedness data and differential phenotypic
      properties demonstrated that strain DS-43T is distinguishable from V. paradoxus.
      On the basis of phenotypic, phylogenetic and genetic data, it is proposed that
      strain DS-43T (=KCTC 12544T = CIP 108838T) be classified in the genus Variovorax
      as a member of a novel species, Variovorax dokdonensis sp. nov.

PMID- 16585701
TI  - Castellaniella gen. nov., to accommodate the phylogenetic lineage of Alcaligenes
      defragrans, and proposal of Castellaniella defragrans gen. nov., comb. nov. and
      Castellaniella denitrificans sp. nov.
AB  - Comparative 16S rRNA gene sequence analysis indicates that two distinct
      sublineages exist within the genus Alcaligenes: the Alcaligenes faecalis lineage,
      comprising Alcaligenes aquatilis and A. faecalis (with the three subspecies A.
      faecalis subsp. faecalis, A. faecalis subsp. parafaecalis and A. faecalis subsp.
      phenolicus), and the Alcaligenes defragrans lineage, comprising A. defragrans.
      This phylogenetic discrimination is supported by phenotypic and chemotaxonomic
      differences. It is proposed that the A. defragrans lineage constitutes a distinct
      genus, for which the name Castellaniella gen. nov. is proposed. The type strain
      for Castellaniella defragrans gen. nov., comb. nov. is 54PinT (=CCUG 39790T = CIP
      105602T = DSM 12141T). Finally, on the basis of data from the literature and new
      DNA-DNA hybridization and phenotypic data, the novel species Castellaniella
      denitrificans sp. nov. (type strain NKNTAUT = DSM 11046T = CCUG 39541T) is
      proposed for two strains previously identified as strains of A. defragrans.

PMID- 16585703
TI  - Emended description of the genus Phyllobacterium and description of four novel
      species associated with plant roots: Phyllobacterium bourgognense sp. nov.,
      Phyllobacterium ifriqiyense sp. nov., Phyllobacterium leguminum sp. nov. and
      Phyllobacterium brassicacearum sp. nov.
AB  - Gram-negative bacteria were isolated from the rhizoplane of Brassica napus in
      France and from root nodules of Argyrolobium uniflorum, Astragalus algerianus and
      Lathyrus numidicus growing in the infra-arid zone of southern Tunisia. Based on
      phylogenetic analysis of the 16S rRNA gene sequences, the seven isolates belong
      to the Alphaproteobacteria and are related to Phyllobacterium myrsinacearum
      strains. The isolates formed three clusters; clusters A and C consist of Tunisian
      strains, whereas cluster B consists of two strains from Brassica napus from
      France. Phylogenetic reconstruction based on the atpD gene strongly supports
      their affiliation to the genus Phyllobacterium. DNA-DNA hybridizations revealed
      that (i) none of the isolates belong to the species P. myrsinacearum, (ii)
      clusters A and C represent two distinct genomospecies and (iii) the two strains
      of cluster B represent two separate genomospecies. Distinctive phenotypic
      features were deduced from numerical analysis of phenotypic data. Based on this
      polyphasic approach, four novel species are proposed: Phyllobacterium leguminum
      sp. nov. (type strain ORS 1419T = CFBP 6745T = LMG 22833T), Phyllobacterium
      ifriqiyense sp. nov. (type strain STM 370T = CFBP 6742T = LMG 22831T),
      Phyllobacterium brassicacearum sp. nov. (type strain STM 196T = CFBP 5551T = LMG
      22836T) and Phyllobacterium bourgognense sp. nov. (type strain STM 201T = CFBP
      5553T = LMG 22837T). The description of the genus Phyllobacterium is emended
      accordingly.

PMID- 16585702
TI  - Hoeflea phototrophica sp. nov., a novel marine aerobic alphaproteobacterium that
      forms bacteriochlorophyll a.
AB  - Within a collection of marine strains that were shown to contain the
      photosynthesis reaction-centre genes pufL and pufM, a novel group of
      alphaproteobacteria was found and was characterized phenotypically. The 16S rRNA
      gene sequence data suggested that the strains belonged to the order Rhizobiales
      and were closest (98.5 % sequence similarity) to the recently described species
      Hoeflea marina. The cells contained bacteriochlorophyll a and a carotenoid,
      presumably spheroidenone, in small to medium amounts. Cells of the novel strains
      were small rods and were motile by means of single polarly inserted flagella.
      Good growth occurred in complex media with 0.5-7.0 % sea salts, at 25-33 degrees
      C (optimum, 31 degrees C) and at pH values in the range 6-9. With the exception
      of acetate and malate, organic carbon sources tested supported poor growth or no
      growth at all. Growth factors were required; these were provided by small amounts
      of yeast extract, but not by standard vitamin solutions. Growth occurred under
      aerobic to microaerobic conditions, but not under anaerobic conditions, either in
      the dark or light. Nitrate was not reduced. Photosynthetic pigments were formed
      at low to medium salt concentrations, but not at the salt concentration of sea
      water (3.5 %). On the basis of smaller cell size, different substrate utilization
      profile and photosynthetic pigment content, the novel strains can be classified
      as representatives of a second species of Hoeflea, for which the name Hoeflea
      phototrophica sp. nov. is proposed. The type strain of Hoeflea phototrophica sp.
      nov. is DFL-43T (=DSM 17068T = NCIMB 14078T).

PMID- 16585704
TI  - Sediminicola luteus gen. nov., sp. nov., a novel member of the family
      Flavobacteriaceae.
AB  - The taxonomic position of four Gram-negative, rod-shaped, golden-yellow-coloured
      bacteria isolated from marine sediments was determined. Analysis of the almost
      complete 16S rRNA gene sequences indicated that these isolates belong to the
      family Flavobacteriaceae. An unclassified bacterium, NBRC 15975, was found to be
      the closest relative, showing 16S rRNA gene sequence similarity of 93 %; other
      related genera shared only 87.9-90.5 % similarity. In contrast, the four isolates
      shared high levels of 16S rRNA gene sequence similarity (99.3-99.7 %) and high
      DNA-DNA reassociation values (93-104 %). The isolates could be differentiated
      phenotypically from other genera by the abilities to reduce nitrate and to
      degrade gelatin, casein and starch. The only respiratory quinone was MK-6, and
      the major fatty acids were iso-C(15 : 0), iso-C(15 : 1), anteiso-C(15 : 0), iso
      C(17 : 1)omega9c and iso-C(17 : 0) 3-OH. The DNA G+C content was 38-40 mol%.
      Differentiating phenotypic characteristics and large phylogenetic distances
      between the isolates and previously published genera indicated that the isolates
      constitute a novel genus, for which the name Sediminicola gen. nov. is proposed.
      The type species is Sediminicola luteus sp. nov. (type strain CNI-3T = NBRC
      100966T = LMG 23246T).

PMID- 16585706
TI  - Pelagibaca bermudensis gen. nov., sp. nov., a novel marine bacterium within the
      Roseobacter clade in the order Rhodobacterales.
AB  - A Gram-negative, chemoheterotrophic, facultatively anaerobic, slightly
      halophilic, oval-shaped marine bacterium, designated HTCC2601T, was isolated from
      the western Sargasso Sea by high-throughput culturing involving dilution to
      extinction. Although the 16S rRNA gene sequence similarity between the isolate
      and Salipiger mucosus was 96.5 %, phylogenetic analyses using different treeing
      algorithms clearly indicated that the strain forms a distinct lineage within a
      clade containing the recently classified genera Salipiger and Palleronia in the
      order Rhodobacterales of the Alphaproteobacteria. The DNA-DNA relatedness between
      strain HTCC2601T and S. mucosus was 26.3 %. Strain HTCC2601T utilized a wide
      range of carbohydrates, including hexose monomers, sugar alcohols, organic acids
      and amino acids, as sole carbon sources. The DNA G+C content of strain HTCC2601T
      was 65.4 mol%, and the predominant constituents of the cellular fatty acids were
      18 : 1omega7c (79.7 %) and 11-methyl 18 : 1omega7c (7.5 %). The strain differed
      from members of the closely related genera Salipiger and Palleronia in its
      morphological, biochemical and ecological characteristics. On the basis of the
      taxonomic data obtained in this study, a novel genus and species, Pelagibaca
      bermudensis gen. nov., sp. nov., is proposed; HTCC2601T (=KCTC 12554T = JCM
      13377T) is the type strain of Pelagibaca bermudensis.

PMID- 16585705
TI  - Sandarakinorhabdus limnophila gen. nov., sp. nov., a novel bacteriochlorophyll a
      containing, obligately aerobic bacterium isolated from freshwater lakes.
AB  - Three strains (so36, so42T and wo26) representing a novel Gram-negative,
      obligately aerobic, bacteriochlorophyll a-containing species of the alpha-4
      subgroup of the Proteobacteria were isolated from freshwater lakes using a high
      throughput cultivation technique. The non-motile and slender rod-shaped cells
      formed orange-red-pigmented colonies. The main carotenoids were nostoxanthin and
      keto-nostoxanthin. According to the absorption spectrum, two different
      photosynthetic light-harvesting complexes, an LHI complex and a B800-830-type
      peripheral LHII complex, were present in the cells. The predominant fatty acids
      of strain so42T were hexadecenoic acid (16 : 1omega7c) and octadecenoic acid (18
      : 1omega7c), whereas 17 : 1omega6c and 14 : 0 iso 2-OH were present in smaller
      amounts. The main polar lipids were phosphatidylethanolamine,
      phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, glycolipid and
      sphingoglycolipids. The major respiratory lipoquinone was ubiquinone-10, whereas
      ubiquinone-9 was present in smaller amounts. The three strains were cytochrome
      oxidase-negative and catalase-positive and formed alkaline and acid phosphatases.
      The strains grew chemoorganoheterotrophically in mineral media supplemented with
      various organic acids, amino acids or complex substrates such as peptone and
      yeast extract. The G+C content of the genomic DNA of strain so42T was 64.3 mol%.
      The three novel isolates contained the same 16S rRNA gene sequence. The 16S rRNA
      gene sequence similarity to the closest phylogenetic relative Sandaracinobacter
      sibiricus was only 92.8 %. Accordingly, the three strains represent a new genus
      and species, for which the name Sandarakinorhabdus limnophila gen. nov., sp.
      nov., is proposed, with strain so42T (=DSM 17366T = CECT 7086T) as the designated
      type strain.

PMID- 16585707
TI  - Arcanobacterium bialowiezense sp. nov. and Arcanobacterium bonasi sp. nov.,
      isolated from the prepuce of European bison bulls (Bison bonasus) suffering from
      balanoposthitis, and emended description of the genus Arcanobacterium Collins et
      al. 1983.
AB  - A taxonomic study was performed on 13 bacterial strains isolated from preputial
      swabs of European bison (Bison bonasus) bulls suffering from balanoposthitis. The
      isolates were Gram-positive, non-motile, facultatively anaerobic, diphtheroid
      shaped cells. Based on biochemical profiles and BOX-PCR-generated genomic
      fingerprints, the isolates were grouped into two clusters represented by four and
      nine strains, respectively. Strains 1(W3/01)T and 2(W106/04)T, selected as
      representatives of the two clusters, shared 97.2 % 16S rRNA gene sequence
      similarity. The highest gene sequence similarities found (95.5-96.4 %) were to
      Arcanobacterium pyogenes DSM 20630T and Arcanobacterium bernardiae DSM 9152T,
      demonstrating that the novel strains are members of the genus Arcanobacterium,
      but are not members of a recognized species. The polar lipid profiles of the two
      novel strains displayed the major characteristics also found in A. pyogenes DSM
      20630T and Arcanobacterium haemolyticum DSM 20595T. Detection of a quinone system
      with MK-10(H4) as the predominant compound confirmed phylogenetic relatedness of
      the novel strains to A. pyogenes and separated them from the type species of the
      genus, A. haemolyticum, which contains MK-9(H4) as the predominant quinone.
      Results from DNA-DNA hybridizations clearly demonstrated that strains 1(W3/01)T
      and 2(W106/04)T represent separate species. Based on these data, two novel
      species of the genus Arcanobacterium are described, for which the names
      Arcanobacterium bialowiezense sp. nov. [type strain 1(W3/01)T = DSM 17162T = NCTC
      13354T] and Arcanobacterium bonasi sp. nov. [type strain 2(W106/04)T = DSM 17163T
      = NCTC 13355T] are proposed.

PMID- 16585708
TI  - Aquitalea magnusonii gen. nov., sp. nov., a novel Gram-negative bacterium
      isolated from a humic lake.
AB  - A Gram-negative, rod-shaped, non-spore-forming betaproteobacterium (TRO-001DR8T)
      was isolated from humic-lake samples collected from northern Wisconsin, USA. On
      the basis of 16S rRNA gene sequence analysis, strain TRO-001DR8T belonged to the
      family Neisseriaceae, and the phylogenetic distance from its closest relative,
      Chromobacterium violaceum, was 95 %. Strain TRO-001DR8T lacked the violet
      pigmentation of C. violaceum and shared only 26 % DNA-DNA relatedness with C.
      violaceum. The DNA G+C content of strain TRO-001DR8T was 59 mol%. The predominant
      fatty acids were C(16 : 1)omega7c + C(16 : 1)omega7c 2-OH iso (52.5 %), C(16 : 0)
      (21.7 %), C(18 : 1)omega7c (8.0 %) and C(12 : 0) (5.1 %). Strain TRO-001DR8T grew
      optimally at 35 degrees C and pH 6.0, did not utilize sucrose, but did use
      glucose, some organic acids and most protein amino acids. Biochemical,
      physiological, chemotaxonomic and phylogenetic analyses showed that strain TRO
      001DR8T could not be assigned to any known genus of the Betaproteobacteria.
      Therefore, the isolate represents a novel genus and species, for which the name
      Aquitalea magnusonii gen. nov., sp. nov. is proposed. The type strain is TRO
      001DR8T (=ATCC BAA-1216T = BCCM/LMG 23054T).

PMID- 16585709
TI  - Delineation of Borrelia burgdorferi sensu lato species by multilocus sequence
      analysis and confirmation of the delineation of Borrelia spielmanii sp. nov.
AB  - To evaluate multilocus sequence analysis (MLSA) for taxonomic purposes in the
      delineation of species within Borrelia burgdorferi sensu lato, seven relevant
      loci of various strains for which extensive DNA-DNA reassociation data were
      available were sequenced. MLSA delineation proved to be fully concordant with
      conventional methods. Our analysis confirmed the delineation of a novel species,
      Borrelia spielmanii sp. nov., previously known as 'Borrelia spielmani' Richter et
      al. 2004, with strain PC-Eq17N5T (=DSM 16813T = CIP 108855T) as the type strain.

PMID- 16585710
TI  - Salegentibacter agarivorans sp. nov., a novel marine bacterium of the family
      Flavobacteriaceae isolated from the sponge Artemisina sp.
AB  - A sponge-associated strain, KMM 7019T, was investigated in a polyphasic taxonomic
      study. The bacterium was strictly aerobic, heterotrophic, Gram-negative, yellow
      pigmented, motile by gliding and oxidase-, catalase-, beta-galactosidase- and
      alkaline phosphatase-positive. A phylogenetic analysis based on 16S rRNA gene
      sequences revealed that strain KMM 7019T is closely related to members of the
      genus Salegentibacter, namely Salegentibacter holothuriorum, Salegentibacter
      mishustinae and Salegentibacter salegens (97.7-98 % sequence similarities). The
      DNA-DNA relatedness between the strain studied and Salegentibacter species ranged
      from 27 to 31 %, clearly demonstrating that KMM 7019T belongs to a novel species
      of the genus Salegentibacter, for which the name Salegentibacter agarivorans sp.
      nov. is proposed. The type strain is KMM 7019T (=KCTC 12560T = LMG 23205T).

PMID- 16585711
TI  - Sphingomonas azotifigens sp. nov., a nitrogen-fixing bacterium isolated from the
      roots of Oryza sativa.
AB  - Three yellow-pigmented strains associated with rice plants were characterized by
      using a polyphasic approach. The nitrogen-fixing abilities of these strains were
      confirmed by acetylene reduction assay and nifH gene detection. The three strains
      were found to be very closely related, with 99.9 % 16S rRNA gene sequence
      similarity and greater than 70 % DNA-DNA hybridization values, suggesting that
      the three strains represent a single species. 16S rRNA gene sequence analysis
      indicated that the strains were closely related to Sphingomonas trueperi, with
      99.5 % similarity. The chemotaxonomic characteristics (G+C content of the DNA of
      68.0 mol%, ubiquinone Q-10 system, 2-OH as the only hydroxy fatty acid and
      homospermidine as the sole polyamine) were similar to those of members of the
      genus Sphingomonas. Based on DNA-DNA hybridization values and physiological
      characteristics, the three novel strains could be differentiated from other
      recognized species of the genus Sphingomonas. The name Sphingomonas azotifigens
      sp. nov. is proposed to accommodate these bacterial strains; the type strain is
      Y39T (=NBRC 15497T = IAM 15283T = CCTCC AB205007T).

PMID- 16585712
TI  - Oceanisphaera donghaensis sp. nov., a halophilic bacterium from the East Sea,
      Korea.
AB  - A taxonomic study was carried out on two isolates, strains BL1(T) and BL11, from
      marine sediment collected from the East Sea, Korea. Comparative 16S rRNA gene
      sequence studies showed that these isolates clearly affiliated with the
      Gammaproteobacteria. BL1T and BL11 were most closely related to Oceanisphaera
      litoralis KMM 3654T (97.6 and 97.7 % 16S rRNA gene sequence similarity,
      respectively). The level of 16S rRNA gene sequence similarity between strains
      BL1T and BL11 was 99.7 %. The two isolates were Gram-negative, aerobic,
      moderately halophilic, and grew in 0.5-8.0 % NaCl and at 4-42 degrees C. Strains
      BL1T and BL11 shared some physiological and biochemical properties with O.
      litoralis KMM 3654T, although they differed in that BL1T and BL11 were able to
      utilize ethanol, proline and alanine. The G+C contents of the genomic DNA of
      strains BL1T and BL11 were 56.6 and 57.1 mol%, respectively. Both strains
      possessed C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH, C(16 : 0) and C(18 :
      1)omega7c as the major fatty acids. DNA-DNA relatedness data indicated that
      strains BL1T and BL11 represent a genomic species that is separate from O.
      litoralis KMM 3654T. On the basis of polyphasic evidence, it is proposed that
      strain BL1T (=KCTC 12522T = DSM 17589T) represents the type strain of a novel
      species, Oceanisphaera donghaensis sp. nov.

PMID- 16585713
TI  - Pseudidiomarina taiwanensis gen. nov., sp. nov., a marine bacterium isolated from
      shallow coastal water of An-Ping Harbour, Taiwan, and emended description of the
      family Idiomarinaceae.
AB  - Two strains of heterotrophic, aerobic, marine bacteria, designated strains PIT1T
      and PIT2, were isolated from sea-water samples collected at the shallow coastal
      region of An-Ping Harbour, Tainan, Taiwan. Both strains were Gram-negative. Cells
      grown in broth cultures were straight rods that were non-motile, lacking
      flagella. Both strains required NaCl for growth and exhibited optimal growth at
      30-35 degrees C, 1-4 % NaCl and pH 8. They grew aerobically and were incapable of
      anaerobic growth by fermentation of glucose or other carbohydrates. Cellular
      fatty acids were predominantly iso-branched, with C(15 : 0) iso and C(17 : 0) iso
      representing the most abundant components. The DNA G+C contents of strains
      PIT1(T) and PIT2 were 49.3 and 48.6 mol%, respectively. Phylogeny based on 16S
      rRNA gene sequences, together with data from phenotypic and chemotaxonomic
      characterization, revealed that the two isolates could be assigned to a novel
      genus in the family Idiomarinaceae, for which the name Pseudidiomarina gen. nov.
      is proposed. Pseudidiomarina taiwanensis sp. nov. is the type species of the
      novel genus (type strain PIT1T = BCRC 17465T = JCM 13360T).

PMID- 16585714
TI  - Tepidicella xavieri gen. nov., sp. nov., a betaproteobacterium isolated from a
      hot spring runoff.
AB  - Strains TU-16T and TU-18, two non-pigmented bacterial isolates with an optimum
      growth temperature of about 45 degrees C and an optimum pH of about 8.5-9.0, were
      recovered from the Furnas geothermal area on the Island of Sao Miguel in the
      Azores. Phylogenetic analysis of the 16S rRNA gene sequence of these strains
      indicated that they represent a novel species in a new genus of the phylum
      Betaproteobacteria. The major fatty acids of strains TU-16T and TU-18 were 16 : 0
      and 18 : 1omega7c. Ubiquinone 8 was the major respiratory quinone and the major
      polar lipids were phosphatidylethanolamine and phosphatidylglycerol. The novel
      isolates were aerobic; thiosulfate was oxidized to sulfate in the presence of a
      metabolizable carbon source. The organism assimilated organic acids and amino
      acids, but did not assimilate carbohydrates or polyols. Based on phylogenetic
      analyses and physiological and biochemical characteristics, it is proposed that
      strain TU-16T (=LMG 23030T = CIP 108724T) represents the type strain of a novel
      species in a new genus, Tepidicella xavieri gen. nov., sp. nov.

PMID- 16585715
TI  - Morphology and phylogenetic position of Spongiochrysis hawaiiensis gen. et sp.
      nov., the first known terrestrial member of the order Cladophorales (Ulvophyceae,
      Chlorophyta).
AB  - Spongiochrysis hawaiiensis gen. et sp. nov. is described from material collected
      at two sites on O'ahu, Hawaiian Islands. This alga produced golden-yellow crusts
      on the bark of Casuarina trees and consisted of globular cells with an axial
      stellate chloroplast. The only form of reproduction was a specialized type of
      autosporulation in which a budding-like division of the mother cell produced
      daughter cells of different sizes. Phylogenetic analyses of the 18S rRNA gene
      showed that Spongiochrysis hawaiiensis is a member of the freshwater clade of the
      Cladophorales/Siphonocladales lineage in the green algal class Ulvophyceae. On
      the basis of its unicellular habit and terrestrial habitat, this species is well
      differentiated from all other members of the same lineage and can be considered
      as the first known successful step of a member of the order Cladophorales into
      terrestrial habitats. The implications of the description of this species with
      regard to both green algal evolution and conservation of little-known tropical
      habitats are discussed. The holotype specimen of Spongiochrysis hawaiiensis is
      GALW015489 and isotype specimens have also been deposited in the BISH and BM
      herbaria.

PMID- 16585717
TI  - Particle matters.

PMID- 16585718
TI  - HCPBM [Heavy Charged Particles in Biology & Medicine] and ENLIGHT [European
      Network for Light Ions] meetings, Oropa (Italy), June 2005.

PMID- 16585719
TI  - What are the risks from medical X-rays and other low dose radiation?
AB  - The magnitude of the risks from low doses of radiation is one of the central
      questions in radiological protection. It is particularly relevant when discussing
      the justification and optimization of diagnostic medical exposures. Medical X
      rays can undoubtedly confer substantial benefits in the healthcare of patients,
      but not without exposing them to effective doses ranging from a few microsieverts
      to a few tens of millisieverts. Do we have any evidence that these levels of
      exposure result in significant health risks to patients? The current consensus
      held by national and international radiological protection organizations is that,
      for these comparatively low doses, the most appropriate risk model is one in
      which the risk of radiation-induced cancer and hereditary disease is assumed to
      increase linearly with increasing radiation dose, with no threshold (the so
      called linear no threshold (LNT) model). However, the LNT hypothesis has been
      challenged both by those who believe that low doses of radiation are more
      damaging than the hypothesis predicts and by those who believe that they are less
      harmful, and possibly even beneficial (often referred to as hormesis). This
      article reviews the evidence for and against both the LNT hypothesis and
      hormesis, and explains why the general scientific consensus is currently in
      favour of the LNT model as the most appropriate dose-response relationship for
      radiation protection purposes at low doses. Finally, the impact of the LNT model
      on the assessment of the risks from medical X-rays and how this affects the
      justification and optimization of such exposures is discussed.

PMID- 16585720
TI  - Diagnosing a parotid lump: fine needle aspiration cytology or core biopsy?
AB  - Fine needle aspiration cytology (FNAC) has been widely adopted for the
      cytological diagnosis of parotid lumps. FNAC does have drawbacks, even under
      optimum conditions and may be associated with poor levels of diagnostic accuracy,
      particularly outside the specialized clinic environment. Ultrasound-guided core
      biopsy (USCB) is a relatively recently described technique in the parotid gland
      which has been well tolerated and has demonstrated a high degree of diagnostic
      accuracy in several studies. This article discusses the merits and pitfalls of
      FNAC, together with the technique of USCB and also highlights the potential
      advantages benefit provided by USCB in parotid diagnosis.

PMID- 16585721
TI  - Intra-arterial MR angiography in the iliac system: initial clinical experience
      with 25 patients.
AB  - The aim of this study was to evaluate intra-arterial magnetic resonance
      angiography (MRA) of the iliac arteries. Therefore, 25 consecutive patients (17
      male, 8 female) suffering from symptomatic occlusive disease of the lower limbs
      were investigated prospectively. Catheter angiography was performed before MRA
      and served as the standard of reference. Contrast-enhanced intra-arterial MRA was
      performed using a 1.5 Tesla MRI system. Contrast agent (gadodiamide) was injected
      by a conventional pigtail-shaped angiography catheter placed in the abdominal
      aorta. Vascular lesions were assessed by four investigators. The degree of
      stenosis was compared with the findings of conventional catheter angiography.
      Additionally, the diagnostic quality of the MR angiograms was assessed by the
      investigators using a semi quantitative five-point scale. All lesions shown by
      catheter angiography were detected and correctly localized by intra-arterial MRA.
      MR angiograms exhibit a specificity of 95% and a sensitivity of 96% for stenoses
      of 50% or more. The diagnostic quality of the images was judged from good to
      excellent, on average. Intra-arterial MRA exhibits a specificity and sensitivity
      comparable with intravenous angiography. The image quality appears to be adequate
      for supporting MR-guided vascular intervention.

PMID- 16585722
TI  - Prevalence and distribution of adnexal findings suggesting endometriosis in
      patients with MR diagnosis of adenomyosis.
AB  - The purpose of this investigation was to establish the prevalence and
      distribution of MR findings associated with pelvic endometriosis in patients with
      a MRI diagnosis of adenomyosis. Retrospective review of the pelvic MRI in 59
      patients (age 32-54 years, mean 42 years) who met strict MRI criteria for
      adenomyosis was performed. T1 weighted fat saturated and T2 weighted images in
      these patients were reviewed for the presence or absence of T1 bright signal
      suggesting endometriosis in any of nine locations (uterine serosa, right and left
      ovary, right and left fallopian tube, right and left broad ligament, and right
      and left pelvic side wall). 20 (20/59) patients (34%), showed characteristic MRI
      features associated with endometriosis. A total of 54 sites of involvement were
      identified (uterine serosa n = 17, ovaries n = 14, broad ligaments n = 10,
      fallopian tubes n = 8, pelvic side walls n = 5) in 20 patients with an average of
      2.7 sites per patient. Implants (n = 43) were more common than endometriomas (n =
      11). Endometriomas occurred most often in the ovaries (ovaries n = 9, broad
      ligament n = 2) whereas implants were seen on all locations (uterine serosa n =
      17, ovaries n = 5, broad ligaments n = 8, fallopian tubes n = 8, pelvic side
      walls n = 5). One third of patients with adenomyosis diagnosed by MRI also had
      MRI findings of endometriosis, with serosal implants being the most common
      finding. Imaging protocols should routinely include T1 weighted fat saturated
      imaging sequences in order to detect coexistent endometriosis in patents
      undergoing pelvic MRI for the diagnosis of adenomyosis.

PMID- 16585723
TI  - Influence of post-treatment delay on the evaluation of the response to focused
      ultrasound surgery of breast cancer by dynamic contrast enhanced MRI.
AB  - The assessment of the effectiveness of MRI-guided focused ultrasound surgery
      (MRIgFUS) of breast carcinomas can be performed by dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) parameters which monitor the presence of
      residual tumour. The aim of this study was to evaluate the effect of the post
      treatment delay on this assessment. DCE-MRI data were acquired immediately and 3
      14 days after MRIgFUS treatment of 26 tumours (<7 days, n = 6; = or > ge;7 days,
      n = 20). The percentage of residual tumour was determined histologically on the
      resected mass and correlated with two DCE-MRI parameters: increase in signal
      intensity (ISI) and positive enhancement integral (PEI). No correlation could be
      found between DCE-MRI data acquired immediately after treatment and the
      percentage of residual tumour. Good correlation coefficients were found for data
      acquired several days after treatment (ISI, r = 0.749; PEI, r = 0.778). However,
      they were higher when the post-treatment time interval was 7 days or more (ISI, r
      = 0.962; PEI, r = 0.934). These results suggest that a post-treatment delay of 7
      days is necessary for the accurate assessment of the presence of residual tumour
      by DCE-MRI parameters.

PMID- 16585724
TI  - Introduction of grids to mobile ICU radiography in a teaching hospital.
AB  - The purpose of this study was to review the change in image quality before and
      after introducing grid use routinely to our mobile X-ray service. This was
      studied in the intensive care unit (ICU) setting, comparing images obtained over
      a 2 week period prior to and after the introduction of the change in technique.
      We introduced a 6:1 grid with appropriate changes in exposure factors. No other
      alterations were made. There were 133 patients in the preliminary group and 196
      patients in the post-grid group. We found a reduction in the proportion of images
      that were of non-diagnostic or barely diagnostic quality. Non-diagnostic
      examinations were reduced from 18% to 1%. Introducing grids to our mobile service
      resulted in improvement in image diagnostic quality, largely by reducing the
      proportion of poor and unacceptable quality images. This effect does not appear
      to have been documented in the literature.

PMID- 16585725
TI  - Colour Doppler ultrasound patterns and clinical follow-up of incidentally found
      hypoechoic, vascular tumours of the spleen: evidence for a benign tumour.
AB  - Between January 1990 and January 2005, incidental hypoechoic, vascular tumours of
      the spleen were identified in 13 patients using B-mode and colour Doppler
      ultrasound (CDS). All lesions found were well demarcated, intrasplenically
      located, and ranged in size between 1 cm and 4 cm. The increased vascular pattern
      on CDS was confirmed in 9 of the 13 cases by contrast enhanced ultrasound (CES),
      while two patients showed reduced vascularity on CES. In 10 patients, lesions
      were confirmed by contrast enhanced CT. Histological examination was performed in
      three patients with the diagnosis of capillary haemangioma (n = 2) and hamartoma
      (n = 1). In the remaining cases, ultrasound follow-up was performed (range 4
      months to 13 years) and demonstrated no evidence of tumour growth in all but one
      patient. During a 4 year follow-up, one lesion increased in size from 1.0 cm to
      1.5 cm and in the same patient an additional 0.5 cm sized hypoechoic increased
      vascular lesion was also found. In the spleen a hypoechoic lesion with an
      increased vascular pattern incidentally found by ultrasound most likely indicates
      a benign tumour with capillary haemangioma/hamartoma as the most likely
      diagnosis. However, it should be emphasised that in all cases a careful
      ultrasound follow-up is warranted.

PMID- 16585726
TI  - A review of current local dose-area product levels for paediatric fluoroscopy in
      a tertiary referral centre compared with national standards. Why are they so
      different?
AB  - A prospective single centre study has been performed to assess dose-area product
      (DAP) values in children having fluoroscopic examinations and to revise local
      diagnostic reference levels (DRLs). DAP measurements for 2658 examinations
      performed in a dedicated fluoroscopy room over a period of 21 months were
      analysed. Data for the eight most commonly performed examinations (2215 cases)
      are presented. DAPs (75th centile) for upper gastrointestinal studies and
      micturating cystograms are substantially lower (by a factor of between x 5 and x
      25) than the current national reference doses (NRDs), with some of the median
      values being 50 times lower. The small DAP values in all examinations demonstrate
      the substantial reduction in dose and consequent risk that can be achieved when
      both equipment performance and operator technique are optimized. Whilst we
      recognize that different institutions will have differing practices, it is
      important that practitioners are aware of the range of DAPs achievable and that
      NRDs do not necessarily represent best practice, and may falsely reassure.

PMID- 16585727
TI  - Peripheral dose from uniform dynamic multileaf collimation fields: implications
      for sliding window intensity-modulated radiotherapy.
AB  - The increase in the number of monitor units in sliding window intensity-modulated
      radiotherapy, compared with conventional techniques for the same target dose, may
      lead to an increase in peripheral dose (PD). PD from a linear accelerator was
      measured for 6 MV X-ray using 0.6 cm3 ionization chamber inserted at 5 cm depth
      into a 35 cm x 35 cm x 105 cm plastic water phantom. Measurements were made for
      field sizes of 6 cm x 6 cm, 10 cm x 10 cm and 14 cm x 14 cm, shaped in both
      static and dynamic multileaf collimation (DMLC) mode, employing strip fields of
      fixed width 0.5 cm, 1.0 cm, 1.5 cm, and 2.0 cm, respectively. The effect of
      collimator rotation and depth of measurement on peripheral dose was investigated
      for 10 cm x 10 cm field. Dynamic fields require 2 to 14 times the number of
      monitor units than does a static open field for the same dose at the isocentre,
      depending on strip field width and field size. Peripheral dose resulting from
      dynamic fields manifests two distinct regions showing a crest and trough within
      30 cm from the field edge and a steady exponential fall beyond 30 cm. All dynamic
      fields were found to deliver a higher PD compared with the corresponding static
      open fields, being highest for smallest strip field width and largest field size;
      also, the percentage increase observed was highest at the largest out-of-field
      distance. For 6 cm x 6 cm field, dynamic fields with 0.5 cm and 2 cm strip field
      width deliver PDs 8 and 2 times higher than that of the static open field. The
      corresponding factors for 14 cm x 14 cm field were 15 and 6, respectively. The
      factors by which PD for DMLC fields increase, relative to jaws-shaped static
      fields for out-of-field distance beyond 30 cm, are almost the same as the
      corresponding increases in the number of monitor units. Reductions of 20% and 40%
      in PD were observed when the measurements were done at a depth of 10 cm and 15
      cm, respectively. When the multileaf collimator executes in-plane (collimator 90
      degrees) motion, peripheral dose decreases by as much as a factor of 3 compared
      with cross-plane data. The knowledge of PD from DMLC field is necessary to
      estimate the increase in whole-body dose and the likelihood of radiation induced
      secondary malignancy.

PMID- 16585728
TI  - The DXL Calscan heel densitometer: evaluation and diagnostic thresholds.
AB  - The DXL Calscan (Demetech AB) is a new dual energy X-ray absorptiometry device
      for determining heel bone mineral density (BMD). The system is based on the
      standard technique of dual energy X-ray absorptiometry (DXA), using a fan beam
      configuration, but introduces an additional laser measurement of heel thickness
      intended to improve accuracy. We have examined the utility, in vitro and in vivo
      performance of the DXL Calscan and established triage thresholds based on the
      UK's National Osteoporosis Society guidelines on peripheral densitometry. The
      Calscan proved convenient, easy to use and was stable over time and within a
      range of operating temperatures. Short-term in vitro precision as %CV, with
      phantom repositioning, was 0.75% and long term precision 0.73%. Precision in
      vivo, determined from duplicate right heel scans of 67 subjects, was 1.19%.
      Effective radiation dose to the patient was <0.1 microSv per scan. 140 white
      females (70 osteoporotic and 70 non-osteoporotic), aged 55-70 years underwent
      scans of both heels. Subjects were defined as osteoporotic or non-osteoporotic on
      the basis of axial DXA (spine L2-L4 and total hip). Triage thresholds for
      reassurance-referral or referral-treatment were 0.391 g cm(-2) and 0.306 g cm(-2)
      for non-dominant and 0.395 g cm(-2), 0.294 g cm(-2) for dominant heel,
      respectively. The non-dominant heel proved slightly superior to the dominant for
      triage purposes. Of the seven non-osteoporotic subjects misclassified as
      osteoporotic by Calscan of either heel, six had severe axial osteopenia. If
      operated by trained personnel and used in appropriate populations exhibiting risk
      factors, the Calscan is well suited for use in the management of post-menopausal
      osteoporosis.

PMID- 16585729
TI  - Time-dependent observer errors in pulmonary nodule detection.
AB  - The work was carried out to investigate differences in visual search
      characteristics between groups of observers with different levels of experience
      in the task of pulmonary nodule detection in chest radiology and we report here
      on these differences in respect of time related decisions. Volunteer observers
      were divided into three groups depending on their level of expertise. There were
      eight radiologists, eight radiographers and eight novices. Their task was to
      detect pulmonary nodules in a test bank of 120 digitized posteroanterior (PA)
      chest radiographs. Five of the eight radiographers were tested twice: once before
      and once after a 6-month training programme in interpretation of the adult chest
      radiograph. During each test session the observers' eye movements were tracked.
      Data on the observers' decisions through Alternate Free Response Operating
      Characteristic (AFROC) methodology were correlated to their eye-movement and
      fixation patterns. True negative decisions from all observers were associated
      with shorter fixation times than false negative decisions. No correct negative
      decisions were made after fixations exceeding 3 s.

PMID- 16585730
TI  - Study of scattered radiation for in-air calibration by a multiple-distance method
      using ionization chambers and an HDR 192Ir brachytherapy source.
AB  - The aim of this study is to estimate the room-scatter correction when measuring
      air kerma rate of an HDR 192Ir brachytherapy source by in-air calibration. The
      variation in scattered radiation due to the specially designed jig and from the
      room walls was also studied. Two therapy ion chambers of volume 0.1 cm3 and 0.6
      cm3 were used in the present study. Air kerma was measured by placing the source
      at several distances between 10 cm and 20 cm from the chamber. The scatter
      radiation was determined by superimposing the theoretically derived model curve
      of known scatter (based on the inverse square law) over the plot of measured air
      kerma strength values. The scatter radiation was estimated in terms of percentage
      of the primary radiation at 10 cm measurement distance. The scatter estimated by
      the 0.6 cm3 chamber at two positions was 0.33% and 0.59%, respectively. Similarly
      the scatter estimated at two other positions by the 0.1 cm3 chamber was 0.58% and
      1.11%. This variation in scatter with position as well as with the chamber was
      due to the varying scatter contribution from components of the measurement set
      up. The scatter radiation becomes constant at a distance greater than 100 cm from
      the walls of the room. We conclude that a fixed chamber with changing source
      positions should be used in multiple-distance measurement of air kerma rate when
      using a measurement jig.

PMID- 16585731
TI  - Implications of quality adjusted survival for clinical trials in radiation
      oncology.
AB  - Clinical trials in radiotherapy sometimes compare changes in radiation dose
      distribution using different radiation techniques. The use of quality adjusted
      survival can, in special circumstances, reduce the requirement of large patient
      numbers in order to show a significant difference in overall outcome. The
      provisos are that marginal improvements in survival or tumour control endpoints
      and a reduction in toxicity scores are present. The converse findings would also
      be amenable to this approach. Random sampling methods are used to construct a
      patient population where the first set of conditions is met. Further work is
      necessary to refine the absolute indications for this technique.

PMID- 16585732
TI  - Response to "Radiation dose measurement and optimization".

PMID- 16585734
TI  - The angel in the marble.

PMID- 16585735
TI  - Desulfovibrio gigas flavodiiron protein affords protection against nitrosative
      stress in vivo.
AB  - Desulfovibrio gigas flavodiiron protein (FDP), rubredoxin:oxygen oxidoreductase
      (ROO), was proposed to be the terminal oxidase of a soluble electron transfer
      chain coupling NADH oxidation to oxygen reduction. However, several members from
      the FDP family, to which ROO belongs, revealed nitric oxide (NO) reductase
      activity. Therefore, the protection afforded by ROO against the cytotoxic effects
      of NO was here investigated. The NO and oxygen reductase activities of
      recombinant ROO in vitro were tested by amperometric methods, and the enzyme was
      shown to effectively reduce NO and O(2). Functional complementation studies of an
      Escherichia coli mutant strain lacking the ROO homologue flavorubredoxin, an NO
      reductase, showed that ROO restores the anaerobic growth phenotype of cultures
      exposed to otherwise-toxic levels of exogenous NO. Additional studies in vivo
      using a D. gigas roo-deleted strain confirmed an increased sensitivity to NO of
      the mutant strain in comparison to the wild type. This effect is more pronounced
      when using the nitrosating agent S-nitrosoglutathione (GSNO), which effectively
      impairs the growth of the D. gigas Deltaroo strain. roo is constitutively
      expressed in D. gigas under all conditions tested. However, real-time reverse
      transcription-PCR analysis revealed a twofold induction of mRNA levels upon
      exposure to GSNO, suggesting regulation at the transcription level by NO. The
      newly proposed role of D. gigas ROO as an NO reductase combined with the O(2)
      reductase activity reveals a versatility which appears to afford protection to D.
      gigas at the onset of both oxidative and nitrosative stresses.

PMID- 16585736
TI  - The riboflavin transporter RibU in Lactococcus lactis: molecular characterization
      of gene expression and the transport mechanism.
AB  - This study describes the characterization of the riboflavin transport protein
      RibU in the lactic acid bacterium Lactococcus lactis subsp. cremoris NZ9000. RibU
      is predicted to contain five membrane-spanning segments and is a member of a
      novel transport protein family, not described in the Transport Classification
      Database. Transcriptional analysis revealed that ribU transcription is
      downregulated in response to riboflavin and flavin mononucleotide (FMN),
      presumably by means of the structurally conserved RFN (riboflavin) element
      located between the transcription start site and the start codon. An L. lactis
      strain carrying a mutated ribU gene exhibits altered transcriptional control of
      the riboflavin biosynthesis operon ribGBAH in response to riboflavin and FMN and
      does not consume riboflavin from its growth medium. Furthermore, it was shown
      that radiolabeled riboflavin is not taken up by the ribU mutant strain, in
      contrast to the wild-type strain, directly demonstrating the involvement of RibU
      in riboflavin uptake. FMN and the toxic riboflavin analogue roseoflavin were
      shown to inhibit riboflavin uptake and are likely to be RibU substrates. FMN
      transport by RibU is consistent with the observed transcriptional regulation of
      the ribGBAH operon by external FMN. The presented transport data are consistent
      with a uniport mechanism for riboflavin translocation and provide the first
      detailed molecular and functional analysis of a bacterial protein involved in
      riboflavin transport.

PMID- 16585737
TI  - A database of bacterial lipoproteins (DOLOP) with functional assignments to
      predicted lipoproteins.
AB  - Lipid modification of the N-terminal Cys residue (N-acyl-S-diacylglyceryl-Cys)
      has been found to be an essential, ubiquitous, and unique bacterial
      posttranslational modification. Such a modification allows anchoring of even
      highly hydrophilic proteins to the membrane which carry out a variety of
      functions important for bacteria, including pathogenesis. Hence, being able to
      identify such proteins is of great value. To this end, we have created a
      comprehensive database of bacterial lipoproteins, called DOLOP, which contains
      information and links to molecular details for about 278 distinct lipoproteins
      and predicted lipoproteins from 234 completely sequenced bacterial genomes. The
      website also features a tool that applies a predictive algorithm to identify the
      presence or absence of the lipoprotein signal sequence in a user-given sequence.
      The experimentally verified lipoproteins have been classified into different
      functional classes and more importantly functional domain assignments using
      hidden Markov models from the SUPERFAMILY database that have been provided for
      the predicted lipoproteins. Other features include the following: primary
      sequence analysis, signal sequence analysis, and search facility and information
      exchange facility to allow researchers to exchange results on newly characterized
      lipoproteins. The website, along with additional information on the biosynthetic
      pathway, statistics on predicted lipoproteins, and related figures, is available
      at http://www.mrc-lmb.cam.ac.uk/genomes/dolop/.

PMID- 16585738
TI  - DNA replication during aggregation phase is essential for Myxococcus xanthus
      development.
AB  - Previous studies have demonstrated that fruiting body-derived Myxococcus xanthus
      myxospores contain two fully replicated copies of its genome, implying
      developmental control of chromosome replication and septation. In this study, we
      employ DNA replication inhibitors to determine if chromosome replication is
      essential to development and the exact time frame in which chromosome replication
      occurs within the developmental cycle. Our results show that DNA replication
      during the aggregation phase is essential for developmental progression, implying
      the existence of a checkpoint that monitors chromosome integrity at the end of
      the aggregation phase.

PMID- 16585739
TI  - A novel three-protein two-component system provides a regulatory twist on an
      established circuit to modulate expression of the cbbI region of Rhodopseudomonas
      palustris CGA010.
AB  - A novel two-component system has been identified in the cbb(I) region of the
      nonsulfur purple photosynthetic bacterium Rhodopseudomonas palustris. Genes
      encoding this system, here designated cbbRRS, are juxtaposed between the
      divergently transcribed transcription activator gene, cbbR, and the form I
      ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) genes, cbbLS. The three
      genes of the cbbRRS system represent a variation of the well-known two-component
      signal transduction systems, as there are a transmembrane hybrid sensor kinase
      and two response regulators, with no apparent DNA binding domain associated with
      any of the three proteins encoded by these genes. In this study, we showed that
      the membrane-bound full-length kinase undergoes autophosphorylation and transfers
      phosphate to both response regulators. A soluble, truncated version of the kinase
      was subsequently prepared and found to catalyze phosphorylation of response
      regulator 1 but not response regulator 2, implying that conformational changes
      and/or sequence-specific regions of the kinase are important for discriminating
      between the two response regulators. Analyses indicated that a complex network of
      control of gene expression must occur, with CbbR required for the expression of
      the cbbLS genes but dispensable for the synthesis of form II RubisCO (encoded by
      cbbM). The CbbRRS proteins specifically affected the activity and accumulation of
      form I RubisCO (CbbLS), as revealed by analyses of nonpolar, unmarked gene
      deletions. A tentative model of regulation suggested that changes in the
      phosphotransfer activity of the sensor kinase, possibly in response to a redox
      metabolic signal, cause modulation of the activity and synthesis of form I
      RubisCO.

PMID- 16585740
TI  - DNA microarray and proteomic analyses of the RpoS regulon in Geobacter
      sulfurreducens.
AB  - The regulon of the sigma factor RpoS was defined in Geobacter sulfurreducens by
      using a combination of DNA microarray expression profiles and proteomics. An rpoS
      mutant was examined under steady-state conditions with acetate as an electron
      donor and fumarate as an electron acceptor and with additional transcriptional
      profiling using Fe(III) as an electron acceptor. Expression analysis revealed
      that RpoS acts as both a positive and negative regulator. Many of the RpoS
      dependent genes determined play roles in energy metabolism, including the
      tricarboxylic acid cycle, signal transduction, transport, protein synthesis and
      degradation, and amino acid metabolism and transport. As expected, RpoS activated
      genes involved in oxidative stress resistance and adaptation to nutrient
      limitation. Transcription of the cytochrome c oxidase operon, necessary for G.
      sulfurreducens growth using oxygen as an electron acceptor, and expression of at
      least 13 c-type cytochromes, including one previously shown to participate in
      Fe(III) reduction (MacA), were RpoS dependent. Analysis of a subset of the rpoS
      mutant proteome indicated that 15 major protein species showed reproducible
      differences in abundance relative to those of the wild-type strain. Protein
      identification using mass spectrometry indicated that the expression of seven of
      these proteins correlated with the microarray data. Collectively, these results
      indicate that RpoS exerts global effects on G. sulfurreducens physiology and that
      RpoS is vital to G. sulfurreducens survival under conditions typically
      encountered in its native subsurface environments.

PMID- 16585741
TI  - Assembly of the type III secretion apparatus of enteropathogenic Escherichia
      coli.
AB  - Enteropathogenic Escherichia coli (EPEC) secretes many Esps (E. coli-secreted
      proteins) and effectors via the type III secretion (TTS) system. We previously
      identified a novel needle complex (NC) composed of a basal body and a needle
      structure containing an expandable EspA sheath-like structure as a central part
      of the EPEC TTS apparatus. To further investigate the structure and protein
      components of the EPEC NC, we purified it in successive centrifugal steps.
      Finally, NCs with long EspA sheath-like structures could be separated from those
      with short needle structures on the basis of their densities. Although the highly
      purified NC appeared to lack an inner ring in the basal body, its core structure,
      composed of an outer ring and a central rod, was observed by transmission
      electron microscopy. Matrix-assisted laser desorption ionization-time-of-flight
      mass spectrometry, Western blot, and immunoelectron microscopic analyses revealed
      that EscC was a major protein component of the outer ring in the core basal body.
      To investigate the mechanisms of assembly of the basal body, interactions between
      the presumed components of the EPEC TTS apparatus were analyzed by a glutathione
      S-transferase pulldown assay. The EscC outer ring protein was associated with
      both the EscF needle protein and EscD, a presumed inner membrane protein. EscF
      was also associated with EscJ, a presumed inner ring protein. Furthermore, escC,
      escD, and escJ mutant strains were unable to produce the TTS apparatus, and
      thereby the secretion of the Esp proteins and Tir effector was abolished. These
      results indicate that EscC, EscD, and EscJ are required for the formation of the
      TTS apparatus.

PMID- 16585742
TI  - Differences in resolution of mwr-containing plasmid dimers mediated by the
      Klebsiella pneumoniae and Escherichia coli XerC recombinases: potential
      implications in dissemination of antibiotic resistance genes.
AB  - Xer-mediated dimer resolution at the mwr site of the multiresistance plasmid
      pJHCMW1 is osmoregulated in Escherichia coli containing either the Escherichia
      coli Xer recombination machinery or Xer recombination elements from K.
      pneumoniae. In the presence of K. pneumoniae XerC (XerC(Kp)), the efficiency of
      recombination is lower than that in the presence of the E. coli XerC (XerC(Ec))
      and the level of dimer resolution is insufficient to stabilize the plasmid, even
      at low osmolarity. This lower efficiency of recombination at mwr is observed in
      the presence of E. coli or K. pneumoniae XerD proteins. Mutagenesis experiments
      identified a region near the N terminus of XerC(Kp) responsible for the lower
      level of recombination catalyzed by XerC(Kp) at mwr. This region encompasses the
      second half of the predicted alpha-helix B and the beginning of the predicted
      alpha-helix C. The efficiencies of recombination at other sites such as dif or
      cer in the presence of XerC(Kp) or XerC(Ec) are comparable. Therefore, XerC(Kp)
      is an active recombinase whose action is impaired on the mwr recombination site.
      This characteristic may result in restriction of the host range of plasmids
      carrying this site, a phenomenon that may have important implications in the
      dissemination of antibiotic resistance genes.

PMID- 16585743
TI  - Morphology of isolated Gli349, a leg protein responsible for Mycoplasma mobile
      gliding via glass binding, revealed by rotary shadowing electron microscopy.
AB  - Several species of mycoplasmas rely on an unknown mechanism to glide across solid
      surfaces in the direction of a membrane protrusion at the cell pole. Our recent
      studies on the fastest species, Mycoplasma mobile, suggested that a 349-kDa
      protein, Gli349, localized at the base of the membrane protrusion called the
      neck, forms legs that stick out from the neck and propel the cell by repeatedly
      binding to and releasing from a solid surface, based on the energy of ATP
      hydrolysis. Here, the Gli349 protein was isolated from mycoplasma cells and its
      structure was analyzed. Gel filtration analysis showed that the isolated Gli349
      protein is monomeric. Rotary shadowing electron microscopy revealed that the
      molecular structure resembles the symbol for an eighth note in music. It contains
      an oval foot 14 nm long in axis. From this foot extend three rods in tandem of
      43, 20, and 20 nm, in that order. The hinge connecting the first and second rods
      is flexible, while the next hinge has a distinct preference in its angle, near 90
      degrees. Molecular images revealed that a monoclonal antibody that can bind to
      the position at one-third of the total peptide length from the N terminus bound
      to a position two-thirds from the foot end, suggesting that the foot corresponds
      to the C-terminal region. The amino acid sequence was assigned to the molecular
      image, and the topology of the molecule in the gliding machinery is discussed.

PMID- 16585744
TI  - A novel FtsZ-like protein is involved in replication of the anthrax toxin
      encoding pXO1 plasmid in Bacillus anthracis.
AB  - Plasmid pXO1 encodes the tripartite anthrax toxin, which is the major virulence
      factor of Bacillus anthracis. In spite of the important role of pXO1 in anthrax
      pathogenesis, very little is known about its replication and maintenance in B.
      anthracis. We cloned a 5-kb region of the pXO1 plasmid into an Escherichia coli
      vector and showed that this plasmid can replicate when introduced into B.
      anthracis. Mutational analysis showed that open reading frame 45 (repX) of pXO1
      was required for the replication of the miniplasmid in B. anthracis.
      Interestingly, repX showed limited homology to bacterial FtsZ proteins that are
      involved in cell division. A mutation in the predicted GTP binding domain of RepX
      abolished its replication activity. Genes almost identical to repX are contained
      on several megaplasmids in members of the Bacillus cereus group, including a B.
      cereus strain that causes an anthrax-like disease. Our results identify a novel
      group of FtsZ-related initiator proteins that are required for the replication of
      virulence plasmids in B. anthracis and possibly in related organisms. Such
      replication proteins may provide novel drug targets for the elimination of
      plasmids encoding the anthrax toxin and other virulence factors.

PMID- 16585745
TI  - Identification of lactaldehyde dehydrogenase in Methanocaldococcus jannaschii and
      its involvement in production of lactate for F420 biosynthesis.
AB  - One of the early steps in the biosynthesis of coenzyme F(420) in
      Methanocaldococcus jannaschii requires generation of 2-phospho-L-lactate, which
      is formed by the phosphorylation of L-lactate. Preliminary studies had shown that
      L-lactate in M. jannaschii is not derived from pyruvate, and thus an alternate
      pathway(s) for its formation was examined. Here we report that L-lactate is
      formed by the NAD(+)-dependent oxidation of l-lactaldehyde by the MJ1411 gene
      product. The lactaldehyde, in turn, was found to be generated either by the
      NAD(P)H reduction of methylglyoxal or by the aldol cleavage of fuculose-1
      phosphate by fuculose-1-phosphate aldolase, the MJ1418 gene product.

PMID- 16585746
TI  - Transcriptional heat shock response in the smallest known self-replicating cell,
      Mycoplasma genitalium.
AB  - Mycoplasma genitalium is a human bacterial pathogen linked to urethritis and
      other sexually transmitted diseases as well as respiratory and joint pathologies.
      Though its complete genome sequence is available, little is understood about the
      regulation of gene expression in this smallest known, self-replicating cell, as
      its genome lacks orthologues for most of the conventional bacterial regulators.
      Still, the transcriptional repressor HrcA (heat regulation at CIRCE [controlling
      inverted repeat of chaperone expression]) is predicted in the M. genitalium
      genome as well as three copies of its corresponding regulatory sequence CIRCE. We
      investigated the transcriptional response of M. genitalium to elevated
      temperatures and detected the differential induction of four hsp genes. Three of
      the up-regulated genes, which encode DnaK, ClpB, and Lon, possess CIRCE within
      their promoter regions, suggesting that the HrcA-CIRCE regulatory mechanism is
      functional. Additionally, one of three DnaJ-encoding genes was up-regulated, even
      though no known regulatory sequences were found in the promoter region.
      Transcript levels returned to control values after 1 h of incubation at 37
      degrees C, reinforcing the transient nature of the heat shock transcriptional
      response. Interestingly, neither of the groESL operon genes, which encode the
      GroEL chaperone and its cochaperone GroES, responded to heat shock. These data
      suggest that M. genitalium selectively regulates a limited number of genes in
      response to heat shock.

PMID- 16585747
TI  - Genetic analysis of the mode of interplay between an ATPase subunit and membrane
      subunits of the lipoprotein-releasing ATP-binding cassette transporter LolCDE.
AB  - The LolCDE complex, an ATP-binding cassette (ABC) transporter, releases
      lipoproteins from the inner membrane, thereby initiating lipoprotein sorting to
      the outer membrane of Escherichia coli. The LolCDE complex is composed of two
      copies of an ATPase subunit, LolD, and one copy each of integral membrane
      subunits LolC and LolE. LolD hydrolyzes ATP on the cytoplasmic side of the inner
      membrane, while LolC and/or LolE recognize and release lipoproteins anchored to
      the periplasmic leaflet of the inner membrane. Thus, functional interaction
      between LolD and LolC/E is critically important for coupling of ATP hydrolysis to
      the lipoprotein release reaction. LolD contains a characteristic sequence called
      the LolD motif, which is highly conserved among LolD homologs but not other ABC
      transporters of E. coli. The LolD motif is suggested to be a region in contact
      with LolC/E, judging from the crystal structures of other ABC transporters. To
      determine the functions of the LolD motif, we mutagenized each of the 32 residues
      of the LolD motif and isolated 26 dominant-negative mutants, whose overexpression
      arrested growth despite the chromosomal lolD(+) background. We then selected
      suppressor mutations of the lolC and lolE genes that correct the growth defect
      caused by the LolD mutations. Mutations of the lolC suppressors were mainly
      located in the periplasmic loop, whereas ones of lolE suppressors were mainly
      located in the cytoplasmic loop, suggesting that the mode of interaction with
      LolD differs between LolC and LolE. Moreover, the LolD motif was found to be
      critical for functional interplay with LolC/E, since some LolD mutations lowered
      the ATPase activity of LolCDE without affecting that of LolD.

PMID- 16585748
TI  - Conserving a volatile metabolite: a role for carboxysome-like organelles in
      Salmonella enterica.
AB  - Salmonellae can use ethanolamine (EA) as a sole source of carbon and nitrogen.
      This ability is encoded by an operon (eut) containing 17 genes, only 6 of which
      are required under standard conditions (37 degrees C; pH 7.0). Five of the extra
      genes (eutM, -N, -L, -K, and -G) become necessary under conditions that favor
      loss of the volatile intermediate, acetaldehyde, which escapes as a gas during
      growth on EA and is lost at a higher rate from these mutants. The eutM, -N, -L,
      and -K genes encode homologues of shell proteins of the carboxysome, an organelle
      shown (in other organisms) to concentrate CO(2). We propose that carboxysome-like
      organelles help bacteria conserve certain volatile metabolites-CO(2) or
      acetaldehyde-perhaps by providing a low-pH compartment. The EutG enzyme converts
      acetaldehyde to ethanol, which may improve carbon retention by forming acetals;
      alternatively, EutG may recycle NADH within the carboxysome.

PMID- 16585749
TI  - Comparison of OG1RF and an isogenic fsrB deletion mutant by transcriptional
      analysis: the Fsr system of Enterococcus faecalis is more than the activator of
      gelatinase and serine protease.
AB  - The FsrABC system of Enterococcus faecalis controls the expression of gelatinase
      and a serine protease via a quorum-sensing mechanism, and recent studies suggest
      that the Fsr system may also regulate other genes important for virulence. To
      investigate the possibility that Fsr influences the expression of additional
      genes, we used transcriptional profiling, with microarrays based on the E.
      faecalis strain V583 sequence, to compare the E. faecalis strain OG1RF with its
      isogenic mutant, TX5266, an fsrB deletion mutant. We found that the presence of
      an intact fsrB influences expression of numerous genes throughout the growth
      phases tested, namely, late log to early stationary phase. In addition, the Fsr
      regulon is independent of the activity of the proteases, GelE and SprE, whose
      expression was confirmed to be activated at all three time points tested. While
      expression of some genes (i.e., ef1097 and ef0750 to -757, encoding hypothetical
      proteins) was activated in late log phase in OG1RF versus the fsrB deletion
      mutant, expression of ef1617 to -1634 (eut-pdu orthologues) was highly repressed
      by the presence of an intact Fsr at entry into stationary phase. This is the
      first time that Fsr has been characterized as a negative regulator. The newly
      recognized Fsr-regulated targets include other factors, besides gelatinase,
      described as important for biofilms (BopD), and genes predicted to encode the
      surface proteins EF0750 to -0757 and EF1097, along with proteins implicated in
      several metabolic pathways, indicating that the FsrABC system may be an important
      regulator in strain OG1RF, with both positive and negative effects.

PMID- 16585751
TI  - The ppuI-rsaL-ppuR quorum-sensing system regulates biofilm formation of
      Pseudomonas putida PCL1445 by controlling biosynthesis of the cyclic lipopeptides
      putisolvins I and II.
AB  - Pseudomonas putida strain PCL1445 produces two cyclic lipopeptides, putisolvin I
      and putisolvin II, which possess surface tension-reducing abilities and are able
      to inhibit biofilm formation and to break down existing biofilms of several
      Pseudomonas spp., including P. aeruginosa. Putisolvins are secreted in the
      culture medium during growth at late exponential phase, indicating that
      production is possibly regulated by quorum sensing. In the present study, we
      identified a quorum-sensing system in PCL1445 that is composed of ppuI, rsaL, and
      ppuR and shows very high similarity with gene clusters of P. putida strains IsoF
      and WCS358. Strains with mutations in ppuI and ppuR showed a severe reduction of
      putisolvin production. Expression analysis of the putisolvin biosynthetic gene in
      a ppuI background showed decreased expression, which could be complemented by the
      addition of synthetic 3-oxo-C(10)-N-acyl homoserine lactone (3-oxo-C(10)-AHL) or
      3-oxo-C(12)-AHL to the medium. An rsaL mutant overproduces AHLs, and production
      of putisolvins is induced early during growth. Analysis of biofilm formation on
      polyvinylchloride showed that ppuI and ppuR mutants produce a denser biofilm than
      PCL1445, which correlates with decreased production of putisolvins, whereas an
      rsaL mutant shows a delay in biofilm production, which correlates with early
      production of putisolvins. The results demonstrate that quorum-sensing signals
      induce the production of cyclic lipopeptides putisolvin I and II and consequently
      control biofilm formation by Pseudomonas putida.

PMID- 16585750
TI  - Functional analysis of luxS in Staphylococcus aureus reveals a role in metabolism
      but not quorum sensing.
AB  - The function of AI-2 in many bacteria and the physiological role of LuxS, the
      enzyme responsible for its production, remain matters of debate. Here, we show
      that in Staphylococcus aureus the luxS gene forms a monocistronic transcriptional
      unit under the control of a sigma(70)-dependent promoter. The gene was
      transcribed throughout growth under a variety of conditions, including
      intracellular growth in MAC-T cells. AI-2 was produced in rich media under
      aerobic and anaerobic conditions, peaking during the transition to stationary
      phase, but was hardly detectable in a sulfur-limited defined medium. In the
      presence of glucose or under anaerobic conditions, cultures retained considerable
      AI-2 activity after entry into stationary phase. Inactivation of luxS in various
      S. aureus strains did not affect virulence-associated traits, such as production
      of hemolysins and extracellular proteases, biofilm formation, and the agr
      signaling system. Conversely, AI-2 production remained unchanged in an agr
      mutant. However, luxS mutants grown in a sulfur-limited defined medium exhibited
      a growth defect. When grown together with the wild type in mixed culture, luxS
      mutants of various S. aureus strains showed reduced ability to compete for growth
      under these conditions. In contrast, a complemented luxS mutant grew as well as
      the parent strain, suggesting that the observed growth defect was of an
      intracellular nature and had not been caused by either second-site mutations or
      the lack of a diffusible factor. However, the LuxS/AI-2 system does not appear to
      contribute to the overall fitness of S. aureus RN6390B during intracellular
      growth in epithelial cells: the wild type and a luxS mutant showed very similar
      growth patterns after their internalization by MAC-T cells.

PMID- 16585752
TI  - The DtxR regulon of Corynebacterium glutamicum.
AB  - Previous studies with Corynebacterium diphtheriae and Mycobacterium species
      revealed that the transcriptional regulator DtxR and its ortholog IdeR play a
      central role in the control of iron metabolism. In the present work, we used
      genome-based approaches to determine the DtxR regulon of Corynebacterium
      glutamicum, a nonpathogenic relative of C. diphtheriae. First, global gene
      expression of a dtxR deletion mutant was compared with that of the wild type
      using DNA microarrays. Second, we used a computer-based approach to identify 117
      putative DtxR binding sites in the C. glutamicum genome. In the third step, 74 of
      the corresponding genome regions were amplified by PCR, 51 of which were shifted
      by the DtxR protein. Finally, we analyzed which of the genes preceded by a
      functional DtxR binding site showed altered mRNA levels in the transcriptome
      comparison. Fifty-one genes organized in 27 putative operons displayed an
      increased mRNA level in the DeltadtxR mutant and thus are presumably repressed by
      DtxR. The majority of these genes are obviously involved in iron acquisition,
      three encode transcriptional regulators, e.g., the recently identified repressor
      of iron proteins RipA, and the others encode proteins of diverse or unknown
      functions. Thirteen genes showed a decreased mRNA level in the DeltadtxR mutant
      and thus might be activated by DtxR. This group included the suf operon, whose
      products are involved in the formation and repair of iron-sulfur clusters, and
      several genes for transcriptional regulators. Our results clearly establish DtxR
      as the master regulator of iron-dependent gene expression in C. glutamicum.

PMID- 16585753
TI  - Aerobic benzoyl-coenzyme A (CoA) catabolic pathway in Azoarcus evansii:
      conversion of ring cleavage product by 3,4-dehydroadipyl-CoA semialdehyde
      dehydrogenase.
AB  - Benzoate, a strategic intermediate in aerobic aromatic metabolism, is metabolized
      in various bacteria via an unorthodox pathway. The intermediates of this pathway
      are coenzyme A (CoA) thioesters throughout, and ring cleavage is nonoxygenolytic.
      The fate of the ring cleavage product 3,4-dehydroadipyl-CoA semialdehyde was
      studied in the beta-proteobacterium Azoarcus evansii. Cell extracts contained a
      benzoate-induced, NADP(+)-specific aldehyde dehydrogenase, which oxidized this
      intermediate. A postulated putative long-chain aldehyde dehydrogenase gene, which
      might encode this new enzyme, is located on a cluster of genes encoding enzymes
      and a transport system required for aerobic benzoate oxidation. The gene was
      expressed in Escherichia coli, and the maltose-binding protein-tagged enzyme was
      purified and studied. It is a homodimer composed of 54 kDa (without tag) subunits
      and was confirmed to be the desired 3,4-dehydroadipyl-CoA semialdehyde
      dehydrogenase. The reaction product was identified by nuclear magnetic resonance
      spectroscopy as the corresponding acid 3,4-dehydroadipyl-CoA. Hence, the
      intermediates of aerobic benzoyl-CoA catabolic pathway recognized so far are
      benzoyl-CoA; 2,3-dihydro-2,3-dihydroxybenzoyl-CoA; 3,4-dehydroadipyl-CoA
      semialdehyde plus formate; and 3,4-dehydroadipyl-CoA. The further metabolism is
      thought to lead to 3-oxoadipyl-CoA, the intermediate at which the conventional
      and the unorthodox pathways merge.

PMID- 16585754
TI  - Green fluorescent chimeras indicate nonpolar localization of pullulanase secreton
      components PulL and PulM.
AB  - The Klebsiella oxytoca pullulanase secreton (type II secretion system) components
      PulM and PulL were tagged at their N termini with green fluorescent protein
      (GFP), and their subcellular location was examined by fluorescence microscopy and
      fractionation. When produced at moderate levels without other secreton components
      in Escherichia coli, both chimeras were envelope associated, as are the native
      proteins. Fluorescent GFP-PulM was evenly distributed over the cell envelope,
      with occasional brighter foci. Under the same conditions, GFP-PulL was barely
      detectable in the envelope by fluorescence microscopy. When produced together
      with all other secreton components, GFP-PulL exhibited circumferential
      fluorescence, with numerous brighter patches. The envelope-associated
      fluorescence of GFP-PulL was almost completely abolished when native PulL was
      also produced, suggesting that the chimera cannot compete with PulL for
      association with other secreton components. The patches of GFP-PulL might
      represent functional secretons, since GFP-PulM also appeared in similar patches.
      GFP-PulM and GFP-PulL both appeared in spherical polar foci when made at high
      levels. In K. oxytoca, GFP-PulM was evenly distributed over the cell envelope,
      with few patches, whereas GFP-PulL showed only weak envelope-associated
      fluorescence. These data suggest that, in contrast to their Vibrio cholerae Eps
      secreton counterparts (M. Scott, Z. Dossani, and M. Sandkvist, Proc. Natl. Acad.
      Sci. USA 98:13978-13983, 2001), PulM and PulL do not localize specifically to the
      cell poles and that the Pul secreton is distributed over the cell surface.

PMID- 16585755
TI  - Transcriptional control of the mycobacterial embCAB operon by PknH through a
      regulatory protein, EmbR, in vivo.
AB  - EmbR, a putative transcriptional regulator from Mycobacterium tuberculosis, is
      homologous to the OmpR class of transcriptional regulators that possess winged
      helix-turn-helix DNA binding motifs. In contrast to other OmpR-like response
      regulators that are usually phosphorylated and controlled by histidine kinases,
      EmbR was recently shown to be phosphorylated by the cognate mycobacterial
      serine/threonine kinase PknH. Despite the in vitro evidence of phosphorylation
      and interaction between the kinase and regulator, the physiological function of
      the PknH-EmbR pair is still unknown. We identify the embCAB operon encoding
      arabinosyltransferases in M. tuberculosis as the cellular target of EmbR.
      Phosphorylation of EmbR enhances its DNA binding activity towards promoter
      regions of embCAB genes. In vivo studies involving expression of PknH in
      Mycobacterium smegmatis established its positive regulatory effect on
      transcription of the embCAB operon via phosphorylation of EmbR. Interestingly,
      increased transcription of embC, catalyzing arabinosylation of lipomannan (LM) to
      lipoarabinomannan (LAM), results in a high LAM/LM ratio, which in turn is a
      crucial factor in mycobacterial virulence. The PknH-mediated increase in the
      transcription of embAB genes significantly alters resistance to ethambutol, a
      frontline antituberculosis drug known to target embAB genes. These findings and
      in vivo upregulation of PknH inside the host macrophages suggest a functionally
      relevant signaling mechanism involving the PknH-EmbR-embCAB system.

PMID- 16585756
TI  - Transcriptional analysis of long-term adaptation of Yersinia enterocolitica to
      low-temperature growth.
AB  - To analyze the transcriptional response of Yersinia enterocolitica cells to
      prolonged growth at low temperature, a collection of luxCDABE transposon mutants
      was cultivated in parallel at optimal (30 degrees C) and suboptimal (10 degrees
      C) temperatures and screened for enhanced promoter activities during growth until
      entering stationary phase. Among 5,700 Y. enterocolitica mutants, 42
      transcriptional units were identified with strongly enhanced or reduced promoter
      activity at 10 degrees C compared to 30 degrees C, and changes in their
      transcriptional levels over time were measured. Green fluorescent protein fusions
      to 10 promoter regions confirmed the data. The temporal order of induction of the
      temperature-responsive genes of Y. enterocolitica was deduced, starting with the
      expression of cold shock genes cspA and cspB and the elevated transcription of a
      glutamate-aspartate symporter. Subsequently, cold-adapted cells drastically up
      regulated genes encoding environmental sensors and regulators, such as UhpABC,
      ArcA, and methyl-accepting chemotaxis protein I (MCPI). Among the most prominent
      cold-responsive elements that were transcriptionally induced during growth in
      early and middle exponential phase are the insecticidal toxin genes tcaA and
      tcaB, as well as genes involved in flagellar synthesis and chemotaxis. The
      expression pattern of the late-exponential- to early-stationary-growth phase is
      dominated by factors involved in biodegradative metabolism, namely, a histidine
      ammonia lyase, three enzymes responsible for uptake and utilization of glycogen,
      the urease complex, and a subtilisin-like protease. Double-knockout mutants and
      complementation studies demonstrate inhibitory effects of MCPI and UhpC on the
      expression of a putative hemolysin transporter. The data partially delineate the
      spectrum of gene expression of Y. enterocolitica at environmental temperatures,
      providing evidence that an as-yet-unknown insect phase is part of the life cycle
      of this human pathogen.

PMID- 16585758
TI  - Acetylornithine transcarbamylase: a novel enzyme in arginine biosynthesis.
AB  - Ornithine transcarbamylase is a highly conserved enzyme in arginine biosynthesis
      and the urea cycle. In Xanthomonas campestris, the protein annotated as ornithine
      transcarbamylase, and encoded by the argF gene, is unable to synthesize
      citrulline directly from ornithine. We cloned and overexpressed this X.
      campestris gene in Escherichia coli and show that it catalyzes the formation of N
      acetyl-L-citrulline from N-acetyl-L-ornithine and carbamyl phosphate. We now
      designate this enzyme as an acetylornithine transcarbamylase. The K(m) values for
      N-acetylornithine and carbamyl phosphate were 1.05 mM and 0.01 mM, respectively.
      Additional putative transcarbamylases that might also be misannotated were found
      in the genomes of members of other xanthomonads, Cytophaga, and Bacteroidetes as
      well as in DNA sequences of bacteria from environmental isolates. It appears that
      these different paths for arginine biosynthesis arose very early in evolution and
      that the canonical ornithine transcarbamylase-dependent pathway became the
      prevalent form. A potent inhibitor, N(alpha)-acetyl-N(delta)-phosphonoacetyl-L
      ornithine, was synthesized and showed a midpoint of inhibition at approximately
      22 nM; this compound may prove to be a useful starting point for designing
      inhibitors specific to this novel family of transcarbamylases.

PMID- 16585757
TI  - Transcription of the contiguous sigB, dtxR, and galE genes in Corynebacterium
      diphtheriae: evidence for multiple transcripts and regulation by environmental
      factors.
AB  - The iron-dependent transcriptional regulator DtxR from Corynebacterium
      diphtheriae is the prototype for a family of metal-dependent regulators found in
      diverse bacterial species. The structure of DtxR and its action as a repressor
      have been extensively characterized, but little is known about expression of
      dtxR. In the current study, we investigated transcription of dtxR as well as the
      sigB and galE genes located immediately upstream and downstream from dtxR,
      respectively. We identified two promoters that determine transcription of dtxR.
      The first, located upstream of sigB, appears to be controlled by an
      extracytoplasmic function sigma factor. The second, located in the intergenic
      region between sigB and dtxR, is similar to promoters used by the primary
      vegetative sigma factors in other actinomycete species. Using quantitative real
      time assays, we demonstrated that the number of transcripts initiated upstream
      from sigB is affected by several environmental factors. In contrast, the presence
      of sodium dodecyl sulfate was the only factor tested that conclusively affects
      the number of transcripts initiated in the sigB-dtxR intergenic region.
      Additionally, we provided evidence for the existence of transcripts that contain
      sigB, dtxR, and galE. Our studies provide the first quantitative transcriptional
      analysis of a gene encoding a DtxR family regulator and give new insights into
      transcriptional regulation in C. diphtheriae.

PMID- 16585759
TI  - Influence of BrpA on critical virulence attributes of Streptococcus mutans.
AB  - Streptococcus mutans, the primary etiological agent of human dental caries, has
      developed multiple mechanisms to colonize and form biofilms on the tooth surface.
      The brpA gene codes for a predicted surface-associated protein with apparent
      roles in biofilm formation, autolysis, and cell division. In this study, we used
      two models to further characterize the biofilm-forming characteristics of a BrpA
      deficient mutant, strain TW14. Compared to those of the parent strain, UA159,
      TW14 formed long chains and sparse microcolonies on hydroxylapatite disks but
      failed to accumulate and form three-dimensional biofilms when grown on glucose as
      the carbohydrate source. The biofilm formation defect was also readily apparent
      by confocal laser scanning microscopy when flow cells were used to grow biofilms.
      When subjected to acid killing at pH 2.8 for 45 min, the survival rate of strain
      TW14 was more than 1 log lower than that of the wild-type strain. TW14 was at
      least 3 logs more susceptible to killing by 0.2% hydrogen peroxide than was
      UA159. The expression of more than 200 genes was found by microarray analysis to
      be altered in cells lacking BrpA (P < 0.01). These results suggest that the loss
      of BrpA can dramatically influence the transcriptome and significantly affects
      the regulation of acid and oxidative stress tolerance and biofilm formation in S.
      mutans, which are key virulence attributes of the organism.

PMID- 16585760
TI  - Role of MinD-membrane association in Min protein interactions.
AB  - Division site placement in Escherichia coli involves interactions of the MinD
      protein with MinC and MinE and with other MinD molecules to form membrane
      associated polymeric structures. In this work, as part of a study of these
      interactions, we established that heterologous membrane-associated proteins such
      as MinD can be targeted to the yeast nuclear membrane, dependent only on the
      presence of a membrane-binding domain and a nuclear targeting sequence. Targeting
      to the nuclear membrane was equally effective using the intrinsic MinD membrane
      targeting domain or the completely unrelated membrane-targeting domain of
      cytochrome b(5). The chimeric proteins differing in their membrane-targeting
      sequences were then used to establish the roles of membrane association and
      specificity of the membrane anchor in MinD interactions, using the yeast two
      hybrid system. The chimeric proteins were also used to show that the membrane
      association of MinD and MinE in E. coli cells had no specificity for the membrane
      anchor, whereas formation of MinDE polar zones and MinE rings required the
      presence of the native MinD membrane-targeting sequence.

PMID- 16585761
TI  - Differential and dynamic localization of topoisomerases in Bacillus subtilis.
AB  - Visualization of topoisomerases in live Bacillus subtilis cells showed that Topo
      I, Topo IV, and DNA gyrase differentially localize on the nucleoids but are
      absent at cytosolic spaces surrounding the nucleoids, suggesting that these
      topoisomerases interact with many regions of the chromosome. While both subunits
      of Topo IV were uniformly distributed throughout the nucleoids, Topo I and gyrase
      formed discrete accumulations, or foci, on the nucleoids in a large fraction of
      the cells, which showed highly dynamic movements. Three-dimensional time lapse
      microscopy showed that gyrase foci accumulate and dissipate within a 1-min time
      scale, revealing dynamic assembly and disassembly of subcellular topoisomerase
      centers. Gyrase centers frequently colocalized with the central DNA replication
      machinery, suggesting a major role for gyrase at the replication fork, while Topo
      I foci were frequently close to or colocalized with the structural maintenance of
      chromosomes (SMC) chromosome segregation complex. The findings suggest that
      different areas of supercoiling exist on the B. subtilis nucleoids, which are
      highly dynamic, with a high degree of positive supercoiling attracting gyrase to
      the replication machinery and areas of negative supercoiling at the bipolar SMC
      condensation centers recruiting Topo I.

PMID- 16585762
TI  - Comparative genomics of NAD biosynthesis in cyanobacteria.
AB  - Biosynthesis of NAD(P) cofactors is of special importance for cyanobacteria due
      to their role in photosynthesis and respiration. Despite significant progress in
      understanding NAD(P) biosynthetic machinery in some model organisms, relatively
      little is known about its implementation in cyanobacteria. We addressed this
      problem by a combination of comparative genome analysis with verification
      experiments in the model system of Synechocystis sp. strain PCC 6803. A detailed
      reconstruction of the NAD(P) metabolic subsystem using the SEED genomic platform
      (http://theseed.uchicago.edu/FIG/index.cgi) helped us accurately annotate
      respective genes in the entire set of 13 cyanobacterial species with completely
      sequenced genomes available at the time. Comparative analysis of operational
      variants implemented in this divergent group allowed us to elucidate both
      conserved (de novo and universal pathways) and variable (recycling and salvage
      pathways) aspects of this subsystem. Focused genetic and biochemical experiments
      confirmed several conjectures about the key aspects of this subsystem. (i) The
      product of the slr1691 gene, a homolog of Escherichia coli gene nadE containing
      an additional nitrilase-like N-terminal domain, is a NAD synthetase capable of
      utilizing glutamine as an amide donor in vitro. (ii) The product of the sll1916
      gene, a homolog of E. coli gene nadD, is a nicotinic acid mononucleotide
      preferring adenylyltransferase. This gene is essential for survival and cannot be
      compensated for by an alternative nicotinamide mononucleotide (NMN)-preferring
      adenylyltransferase (slr0787 gene). (iii) The product of the slr0788 gene is a
      nicotinamide-preferring phosphoribosyltransferase involved in the first step of
      the two-step non-deamidating utilization of nicotinamide (NMN shunt). (iv) The
      physiological role of this pathway encoded by a conserved gene cluster, slr0787
      slr0788, is likely in the recycling of endogenously generated nicotinamide, as
      supported by the inability of this organism to utilize exogenously provided
      niacin. Positional clustering and the co-occurrence profile of the respective
      genes across a diverse collection of cellular organisms provide evidence of
      horizontal transfer events in the evolutionary history of this pathway.

PMID- 16585763
TI  - Functional domains of the Bacillus subtilis transcription factor AraR and
      identification of amino acids important for nucleoprotein complex assembly and
      effector binding.
AB  - The Bacillus subtilis AraR transcription factor represses at least 13 genes
      required for the extracellular degradation of arabinose-containing
      polysaccharides, transport of arabinose, arabinose oligomers, xylose, and
      galactose, intracellular degradation of arabinose oligomers, and further
      catabolism of this sugar. AraR exhibits a chimeric organization comprising a
      small N-terminal DNA-binding domain that contains a winged helix-turn-helix motif
      similar to that seen with the GntR family and a larger C-terminal domain
      homologous to that of the LacI/GalR family. Here, a model for AraR was derived
      based on the known crystal structures of the FadR and PurR regulators from
      Escherichia coli. We have used random mutagenesis, deletion, and construction of
      chimeric LexA-AraR fusion proteins to map the functional domains of AraR required
      for DNA binding, dimerization, and effector binding. Moreover, predictions for
      the functional role of specific residues were tested by site-directed
      mutagenesis. In vivo analysis identified particular amino acids required for
      dimer assembly, formation of the nucleoprotein complex, and composition of the
      sugar-binding cleft. This work presents a structural framework for the function
      of AraR and provides insight into the mechanistic mode of action of this modular
      repressor.

PMID- 16585764
TI  - Detailed genomic analysis of the Wbeta and gamma phages infecting Bacillus
      anthracis: implications for evolution of environmental fitness and antibiotic
      resistance.
AB  - Phage-mediated lysis has been an essential laboratory tool for rapidly
      identifying Bacillus anthracis for more than 40 years, relying on the gamma phage
      derivative of a Bacillus cereus prophage called W. The complete genomic sequences
      of the temperate W phage, referred to as Wbeta, and its lytic variant gamma were
      determined and found to encode 53 open reading frames each, spanning 40,864 bp
      and 37,373 bp, respectively. Direct comparison of the genomes showed that gamma
      evolved through mutations at key loci controlling host recognition, lysogenic
      growth, and possibly host phenotypic modification. Included are a cluster of
      point mutations at the gp14 tail fiber locus of gamma, encoding a protein that,
      when fused to green fluorescent protein, binds specifically to B. anthracis. A
      large 2,003-bp deletion was also identified at the gamma lysogeny module,
      explaining its shift from a temperate to a lytic lifestyle. Finally, evidence of
      recombination was observed at a dicistronic Wbeta locus, encoding putative
      bacterial cell surface-modifying proteins, replaced in gamma with a locus, likely
      obtained from a B. anthracis prophage, encoding demonstrable fosfomycin
      resistance. Reverse transcriptase PCR analysis confirmed strong induction at the
      dicistronic Wbeta locus and at four other phage loci in B. anthracis and/or B.
      cereus lysogens. In all, this study represents the first genomic and functional
      description of two historically important phages and is part of a broader
      investigation into contributions of phage to the B. anthracis life cycle. Initial
      findings suggest that lysogeny of B. anthracis promotes ecological adaptation,
      rather than virulence, as with other gram-positive pathogens.

PMID- 16585765
TI  - Structural alterations of the cysteine desulfurase IscS of Salmonella enterica
      serovar Typhimurium reveal substrate specificity of IscS in tRNA thiolation.
AB  - The cysteine desulfurase IscS in Salmonella enterica serovar Typhimurium is
      required for the formation of all four thiolated nucleosides in tRNA, which is
      thought to occur via two principally different biosynthetic pathways. The
      synthesis of 4-thiouridine (s(4)U) and 5-methylaminomethyl-2-thiouridine
      (mnm(5)s(2)U) occurs by a transfer of sulfur from IscS via various proteins to
      the target nucleoside in the tRNA, and no iron-sulfur cluster protein
      participates, whereas the synthesis of 2-thiocytidine (s(2)C) and N(6)-(4
      hydroxyisopentenyl)-2-methylthioadenosine (ms(2)io(6)A) is dependent on iron
      sulfur cluster proteins, whose formation and maintenance depend on IscS.
      Accordingly, inactivation of IscS should result in decreased synthesis of all
      thiolated nucleosides. We selected mutants defective either in the synthesis of a
      thiolated nucleoside (mnm(5)s(2)U) specific for the iron-sulfur protein
      independent pathway or in the synthesis of a thiolated nucleoside (ms(2)io(6)A)
      specific for the iron-sulfur protein-dependent pathway. Although we found altered
      forms of IscS that influenced the synthesis of all thiolated nucleosides,
      consistent with the model, we also found mutants defective in subsets of
      thiolated nucleosides. Alterations in the C-terminal region of IscS reduced the
      level of only ms(2)io(6)A, suggesting that the synthesis of this nucleoside is
      especially sensitive to minor aberrations in iron-sulfur cluster transfer
      activity. Our results suggest that IscS has an intrinsic substrate specificity in
      how it mediates sulfur mobilization and/or iron-sulfur cluster formation and
      maintenance required for thiolation of tRNA.

PMID- 16585766
TI  - Upregulated transcription of plasmid and chromosomal ribulose monophosphate
      pathway genes is critical for methanol assimilation rate and methanol tolerance
      in the methylotrophic bacterium Bacillus methanolicus.
AB  - The natural plasmid pBM19 carries the key mdh gene needed for the oxidation of
      methanol into formaldehyde by Bacillus methanolicus. Five more genes, glpX, fba,
      tkt, pfk, and rpe, with deduced roles in the cell primary metabolism, are also
      located on this plasmid. By using real-time PCR, we show that they are
      transcriptionally upregulated (6- to 40-fold) in cells utilizing methanol; a
      similar induction was shown for two chromosomal genes, hps and phi. These seven
      genes are involved in the fructose bisphosphate aldolase/sedoheptulose
      bisphosphatase variant of the ribulose monophosphate (RuMP) pathway for
      formaldehyde assimilation. Curing of pBM19 causes higher methanol tolerance and
      reduced formaldehyde tolerance, and the methanol tolerance is reversed to wild
      type levels by reintroducing mdh. Thus, the RuMP pathway is needed to detoxify
      the formaldehyde produced by the methanol dehydrogenase-mediated conversion of
      methanol, and the in vivo transcription levels of mdh and the RuMP pathway genes
      reflect the methanol tolerance level of the cells. The transcriptional inducer of
      hps and phi genes is formaldehyde, and not methanol, and introduction of multiple
      copies of these two genes into B. methanolicus made the cells more tolerant of
      growth on high methanol concentrations. The recombinant strain also had a
      significantly higher specific growth rate on methanol than the wild type. While
      pBM19 is critical for growth on methanol and important for formaldehyde
      detoxification, the maintenance of this plasmid represents a burden for B.
      methanolicus when growing on mannitol. Our data contribute to a new and
      fundamental understanding of the regulation of B. methanolicus methylotrophy.

PMID- 16585767
TI  - A CsgD-independent pathway for cellulose production and biofilm formation in
      Escherichia coli.
AB  - Bacterial growth on a surface often involves the production of a polysaccharide
      rich extracellular matrix that provides structural support for the formation of
      biofilm communities. In Salmonella, cellulose is one of the major constituents of
      the biofilm matrix. Its production is regulated by CsgD and the diguanylate
      cyclase AdrA that activates cellulose synthesis at a posttranscriptional level.
      Here, we studied a collection of Escherichia coli isolates, and we found that the
      ability to produce cellulose is a common trait shared by more than 50% of the
      tested strains. We investigated the genetic determinants of cellulose production
      and its role in biofilm formation in the commensal strain E. coli 1094. By
      contrast with the Salmonella cellulose regulatory cascade, neither CsgD nor AdrA
      is required in E. coli 1094 to regulate cellulose production. In this strain, an
      alternative cellulose regulatory pathway is used, which involves the GGDEF domain
      protein, YedQ. Although AdrA(1094) is functional, it is weakly expressed in E.
      coli 1094 compared to YedQ, which constitutively activates cellulose production
      under all tested environmental conditions. The study of cellulose regulation in
      several other E. coli isolates showed that, besides the CsgD/AdrA regulatory
      pathway, both CsgD-independent/YedQ-dependent and CsgD-independent/YedQ
      independent pathways are found, indicating that alternative cellulose pathways
      are common in E. coli and possibly in other cellulose-producing
      Enterobacteriaceae.

PMID- 16585768
TI  - The Erwinia chrysanthemi 3937 PhoQ sensor kinase regulates several virulence
      determinants.
AB  - The PhoPQ two-component system regulates virulence factors in Erwinia
      chrysanthemi, a pectinolytic enterobacterium that causes soft rot in several
      plant species. We characterized the effect of a mutation in phoQ, the gene
      encoding the sensor kinase PhoQ of the PhoPQ two-component regulatory system, on
      the global transcriptional profile of E. chrysanthemi using cDNA microarrays and
      further confirmed our results by quantitative reverse transcription-PCR analysis.
      Our results indicate that a mutation in phoQ affects transcription of at least 40
      genes, even in the absence of inducing conditions. Enhanced expression of several
      genes involved in iron metabolism was observed in the mutant, including that of
      the acs operon that is involved in achromobactin biosynthesis and transport. This
      siderophore is required for full virulence of E. chrysanthemi, and its expression
      is governed by the global repressor protein Fur. Changes in gene expression were
      also observed for membrane transporters, stress-related genes, toxins, and
      transcriptional regulators. Our results indicate that the PhoPQ system governs
      the expression of several additional virulence factors and may also be involved
      in interactions with other regulatory systems.

PMID- 16585769
TI  - Effects of phosphorelay perturbations on architecture, sporulation, and spore
      resistance in biofilms of Bacillus subtilis.
AB  - The spore-forming bacterium Bacillus subtilis is able to form highly organized
      multicellular communities called biofilms. This coordinated bacterial behavior is
      often lost in domesticated or laboratory strains as a result of planktonic growth
      in rich media for many generations. However, we show here that the laboratory
      strain B. subtilis 168 is still capable of forming spatially organized
      multicellular communities on minimal medium agar plates, exemplified by colonies
      with vein-like structures formed by elevated bundles of cells. In line with the
      current model for biofilm formation, we demonstrate that overproduction of the
      phosphorelay components KinA and Spo0A stimulates bundle formation, while
      overproduction of the transition state regulators AbrB and SinR leads to
      repression of formation of elevated bundles. Time-lapse fluorescence microscopy
      studies of B. subtilis green fluorescent protein reporter strains show that
      bundles are preferential sites for spore formation and that flat structures
      surrounding the bundles contain vegetative cells. The elevated bundle structures
      are formed prior to sporulation, in agreement with a genetic developmental
      program in which these processes are sequentially activated. Perturbations of the
      phosphorelay by disruption and overexpression of genes that lead to an increased
      tendency to sporulate result in the segregation of sporulation mutations and
      decreased heat resistance of spores in biofilms. These results stress the
      importance of a balanced control of the phosphorelay for biofilm and spore
      development.

PMID- 16585770
TI  - EspF of enteropathogenic Escherichia coli binds sorting nexin 9.
AB  - EspF of enteropathogenic Escherichia coli targets mitochondria and subverts a
      number of cellular functions. EspF consists of six putative Src homology 3 (SH3)
      domain binding motifs. In this study we identified sorting nexin 9 (SNX9) as a
      host cell EspF binding partner protein, which binds EspF via its amino-terminal
      SH3 region. Coimmunoprecipitation and confocal microscopy showed specific EspF
      SNX9 interaction and non-mitochondrial protein colocalization in infected
      epithelial cells.

PMID- 16585771
TI  - Differential biofilm formation and motility associated with
      lipopolysaccharide/exopolysaccharide-coupled biosynthetic genes in
      Stenotrophomonas maltophilia.
AB  - Stenotrophomonas maltophilia WR-C is capable of forming biofilm on polystyrene
      and glass. The lipopolysaccharide/exopolysaccharide-coupled biosynthetic genes
      rmlA, rmlC, and xanB are necessary for biofilm formation and twitching motility.
      Mutants with mutations in rmlAC and xanB display contrasting biofilm phenotypes
      on polystyrene and glass and differ in swimming motility.

PMID- 16585772
TI  - Mechanism of hilA repression by 1,2-propanediol consists of two distinct
      pathways, one dependent on and the other independent of catabolic production of
      propionate, in Salmonella enterica serovar Typhimurium.
AB  - A glycerol dehydrogenase gene was selected as a multicopy suppressor rescuing the
      reduced hilA expression in the Salmonella enterica serovar Typhimurium cpxA
      mutant. A substrate of the enzyme, 1,2-propanediol, repressed hilA expression.
      The 1,2-propanediol-mediated repression at 150 mM, but not that at 300 mM, was
      abrogated by blocking the catabolism producing propionate from 1,2-propanediol.

PMID- 16585773
TI  - An allele of gyrA prevents Salmonella enterica serovar Typhimurium from using
      succinate as a carbon source.
AB  - A mutant gyrA allele resulting in an A271E substitution in the DNA gyrase protein
      generated a strain unable to grow on the C(4)-dicarboxylates succinate, malate,
      and fumarate. Bacteria harboring gyrA751 displayed decreased negative
      supercoiling in cells. Expression of the dctA gene, which encodes the C(4)
      dicarboxylate transporter, was reduced in a gyrA751 mutant, providing the first
      evidence that dctA expression is supercoiling sensitive and uncovering a simple
      metabolic screen for lesions in gyrase that reduce negative supercoiling.

PMID- 16585774
TI  - Sigma L is important for cold shock adaptation of Bacillus subtilis.
AB  - Although sigma factor-dependent transcriptional regulation was shown to be
      essential for adaptation to different environmental stimuli, no such sigma factor
      has been related to the regulation of the cold shock response in Bacillus
      subtilis. In this study, we present genetic evidence for participation of
      sigma(L) (sigma(54)) and the two sigma(L)-dependent transcriptional enhancers
      BkdR and YplP in the cold shock response of Bacillus subtilis JH642. Single-gene
      deletion of either sigL, bkdR, or yplP resulted in a cold-sensitive phenotype.

PMID- 16585775
TI  - Independent regulation of MucD, an HtrA-like protease in Pseudomonas aeruginosa,
      and the role of its proteolytic motif in alginate gene regulation.
AB  - Expression of mucD, encoding a homologue of the HtrA(DegP) family of endoserine
      proteases, was investigated in Pseudomonas aeruginosa. Expressed from the algT
      mucABCD operon, MucD was detected in mucoid (FRD1) and nonmucoid (PAO1) parental
      strains and also when polar insertions were placed upstream in algT or mucB. A
      transcriptional start site for a mucD promoter (PmucD) was mapped within mucC.
      Expression of single-copy mucD217, encoding MucD altered in the protease motif
      (S217A), was defective in temperature resistance and alginate gene regulation.

PMID- 16585776
TI  - Two putative c-type multiheme cytochromes required for the expression of OmcB, an
      outer membrane protein essential for optimal Fe(III) reduction in Geobacter
      sulfurreducens.
AB  - Deletion of two homologous Geobacter sulfurreducens c-type cytochrome genes, omcG
      and omcH, decreased the rate of Fe(III) reduction and decreased the level of an
      outer membrane cytochrome critical for Fe(III) reduction, OmcB, without affecting
      its transcription. Expression of either gene restored Fe(III) reduction and OmcB
      expression, suggesting functional similarity.

PMID- 16585777
TI  - BacA-mediated bleomycin sensitivity in Sinorhizobium meliloti is independent of
      the unusual lipid A modification.
AB  - Sinorhizobium meliloti bacA mutants are symbiotically defective, deoxycholate
      sensitive, and bleomycin resistant. We show that the bleomycin resistance
      phenotype is independent of the lipid A alteration and that the changes giving
      rise to both phenotypes are likely to be involved in the inability of bacA
      mutants to persist within their hosts.

PMID- 16585778
TI  - Characterization of a gene encoding an acetylase required for pyoverdine
      synthesis in Pseudomonas aeruginosa.
AB  - Strains of Pseudomonas aeruginosa secrete one of three pyoverdine siderophores
      (types I to III). We have characterized a gene, pvdY(II) (for the pvdY gene
      present in type II P. aeruginosa strains), that is only present in strains that
      make type II pyoverdine. A mutation in pvdY(II) prevented pyoverdine synthesis.
      Bioinformatic, genetic, and biochemical approaches indicate that the PvdYII
      enzyme catalyzes acetylation of hydroxyornithine. Expression of pvdY(II) is
      repressed by the presence of iron and upregulated by the presence of type II
      pyoverdine. Characterization of pvdY(II) provides insights into the molecular
      basis for production of different pyoverdines by different strains of P.
      aeruginosa.

PMID- 16585779
TI  - Levels of glycine betaine in growing cells and spores of Bacillus species and
      lack of effect of glycine betaine on dormant spore resistance.
AB  - Bacteria of various Bacillus species are able to grow in media with very high
      osmotic strength in part due to the accumulation of low-molecular-weight
      osmolytes such as glycine betaine (GB). Cells of Bacillus species grown in rich
      and minimal media contained low levels of GB, but GB levels were 4- to 60-fold
      higher in cells grown in media with high salt. GB levels in Bacillus subtilis
      cells grown in minimal medium were increased approximately 7-fold by GB in the
      medium and 60-fold by GB plus high salt. GB was present in spores of Bacillus
      species prepared in media with or without high salt but at lower levels than in
      comparable growing cells. With spores prepared in media with high salt, GB levels
      were highest in B. subtilis spores and > or =20-fold lower in B. cereus and B.
      megaterium spores. Although GB levels in B. subtilis spores were elevated 15- to
      30-fold by GB plus high salt in sporulation media, GB levels did not affect spore
      resistance. GB levels were similar in wild-type B. subtilis spores and spores
      that lacked major small, acid-soluble spore proteins but were much lower in
      spores that lacked dipicolinic acid.

PMID- 16585780
TI  - Identification of Nudix hydrolase family members with an antimutator role in
      Mycobacterium tuberculosis and Mycobacterium smegmatis.
AB  - Mycobacterium tuberculosis and Mycobacterium smegmatis MutT1, MutT2, MutT3, and
      Rv3908 (MutT4) enzymes were screened for an antimutator role. Results indicate
      that both MutT1, in M. tuberculosis and M. smegmatis, and MutT4, in M. smegmatis,
      have that role. Furthermore, an 8-oxo-guanosine triphosphatase function for MutT1
      and MutT2 is suggested.

PMID- 16585781
TI  - Thematic review series: the pathogenesis of atherosclerosis. An interpretive
      history of the cholesterol controversy, part V: the discovery of the statins and
      the end of the controversy.
AB  - The first four reviews in this series (Steinberg, D. 2004. J. Lipid Res. 45: 1583
      1593; Steinberg, D. 2005. J. Lipid Res. 46: 179-190; Steinberg, D. 2005. J. Lipid
      Res. 46: 2037-2051; Steinberg, D. 2006. J. Lipid Res. 47: 1-14) traced the
      gradual accumulation of evidence, evidence of several different kinds, supporting
      the lipid hypothesis. They tracked the history from Anitschkow's 1913 classic
      work on the cholesterol-fed rabbit model to the breakthrough 1984 Coronary
      Primary Prevention Trial, the first large, randomized, double-blind primary
      intervention trial showing that decreasing blood cholesterol (using
      cholestyramine) significantly reduces coronary heart disease events. At that
      point, for the first time, decreasing blood cholesterol levels became an official
      national public health goal. Still, only a small fraction of patients at high
      risk were getting appropriate cholesterol-lowering treatment, and a number of
      important clinical questions remained unanswered. This final review in the series
      traces the early studies that led to the discovery of the statins and briefly
      reviews the now familiar large-scale clinical trials demonstrating their safety
      and their remarkable effectiveness in reducing coronary heart disease morbidity
      and mortality.

PMID- 16585782
TI  - Enzyme activity assay for cholesterol 27-hydroxylase in mitochondria.
AB  - Mitochondrial cholesterol 27-hydroxylase (CYP27A1) plays an important role in the
      maintenance of intracellular cholesterol homeostasis. Cholesterol delivery to the
      mitochondrial inner membrane is believed to be a rate-limiting step for the
      "acidic" pathway of bile acid synthesis. This work reports that proteinase K
      treatment of mitochondria markedly increases CYP27A1 specific activity. With
      endogenous mitochondrial cholesterol, treatment with proteinase K increased
      CYP27A1 specific activity by 5-fold. Moreover, the addition of the exogenous
      cholesterol in beta-cyclodextrin plus proteinase K treatment increased the
      specific activity by 7-fold. Kinetic studies showed that the increased activity
      was time-, proteinase K-, and substrate concentration-dependent. Proteinase K
      treatment decreased the apparent K(m) of CYP27A1 for cholesterol from 400 to 150
      microM. Using this new assay, we found that during rat hepatocyte preparation and
      cell culture, mitochondria gradually lose CYP27A1 activity compared with
      mitochondria freshly isolated from rat liver tissue.

PMID- 16585783
TI  - Arachidonic acid cascade and epithelial barrier function during Caco-2 cell
      differentiation.
AB  - The small intestinal epithelium is a highly dynamic system continuously renewed
      by a process involving cell proliferation and differentiation. The intestinal
      epithelium constitutes a permeability barrier regulating the vectorial transport
      of ions, water, and solutes. Morphological changes during cell differentiation,
      as well as changes in the activity of brush-border enzymes and the expression of
      transport proteins, are well established. However, little is known about the
      arachidonic acid (AA) cascade underlying epithelial cell differentiation or its
      role in the development of epithelial barrier function. The main purpose of this
      study was to examine the activity of the high-molecular-weight phospholipases
      A(2) (PLA(2)) and cyclooxygenase (COX) pathway during differentiation, with
      particular emphasis on paracellular permeability. PLA(2) activity, AA release,
      COX-2 expression, prostaglandin E(2) (PGE(2)) production, and paracellular
      permeability were studied in preconfluent, confluent, and differentiated Caco-2
      cell cultures. Our results show that Caco-2 differentiation induces a decrease in
      both calcium-independent PLA(2) activity and COX-2 expression and, consequently,
      a decrease in AA release and PGE(2) synthesis in parallel with a reduction in
      paracellular permeability. Moreover, the addition of PGE(2) to differentiated
      cells, at concentrations similar to those detected in nondifferentiated cultures,
      induces the disruption of epithelial barrier function. These results suggest that
      AA release by calcium-independent PLA(2), COX-2 expression, and subsequent PGE(2)
      release are important for the maintenance of paracellular permeability in
      differentiated Caco-2 cells.

PMID- 16585784
TI  - Genome-wide identification of peroxisome proliferator response elements using
      integrated computational genomics.
AB  - Peroxisome proliferator-activated receptor (PPAR) agonists are currently used
      therapeutically in humans, even though many of their direct gene targets are
      unknown. Because PPARs can directly regulate gene expression through peroxisome
      proliferator response elements (PPREs), we pursued the computational prediction
      of PPREs on a genome-wide scale. Contrary to current hypotheses, PPREs are not
      isotype-specific, nor do flanking nucleotides confer additional information.
      However, a position weight matrix-based search for PPREs within upstream
      conserved elements yielded sufficient selectivity for a genome-wide search.
      Additionally, a novel motif occurring with greater prevalence than PPREs was
      revealed. Microarray and gene ontology analyses further validated our search
      technique and provided new functional clusters of genes that were not previously
      known to be directly regulated by PPARs (e.g., chromatin remodeling, DNA damage
      response, Wnt, and mitogen-activated protein kinase signaling). This first genome
      wide library of high-confidence predicted PPAR target genes will be a valuable
      resource to PPAR biologists.

PMID- 16585785
TI  - Perirhinal cortex and feature-ambiguous discriminations.

PMID- 16585787
TI  - Is extinction of fear erasure or inhibition? Why both, of course.

PMID- 16585788
TI  - SGK protein kinase facilitates the expression of long-term potentiation in
      hippocampal neurons.
AB  - Previous studies showed that the serum- and glucocorticoid-inducible kinase (sgk)
      gene plays an important role in long-term memory formation. The present study
      further examined the role of SGK in long-term potentiation (LTP). The dominant
      negative mutant of sgk, SGKS422A, was used to inactivate SGK. Results revealed a
      time-dependent increase in SGK phosphorylation after tetanization with a
      significant effect observed 3 h and 5 h later. Transfection of SGKS422A impaired
      the expression, but not the induction, of LTP. Furthermore, the constitutively
      active sgk, SGKS422D, up-regulated postsynaptic density-95 expression in the
      hippocampus. These results together support the role of SGK in neuronal
      plasticity.

PMID- 16585789
TI  - Dorsal hippocampus function in learning and expressing a spatial discrimination.
AB  - Learning to discriminate between spatial locations defined by two adjacent arms
      of a radial maze in the conditioned cue preference paradigm requires two kinds of
      information: latent spatial learning when the rats explore the maze with no food
      available, and learning about food availability in two spatial locations when the
      rats are then confined in one arm with food and the other with no food. Previous
      research showed that a functional dorsal hippocampus is not required for latent
      learning. The present experiments show that it is required for learning about
      food availability, and during retrieval of both types of information.

PMID- 16585790
TI  - A mutant mouse with a highly specific contextual fear-conditioning deficit found
      in an N-ethyl-N-nitrosourea (ENU) mutagenesis screen.
AB  - Targeted mutagenesis in mice has shown that genes from a wide variety of gene
      families are involved in memory formation. The efficient identification of genes
      involved in learning and memory could be achieved by random mutagenesis combined
      with high-throughput phenotyping. Here, we provide the first report of a
      mutagenesis screen that has generated memory mutants in the mouse. We tested a
      group of N-ethyl-N-nitrosourea (ENU) mutagenized mice in the conditioned fear
      paradigm. We screened for both dominant and recessive mutations that caused
      impairments in contextual or tone fear conditioning. Heritability testing
      confirmed three fear conditioning mutants, i.e., Forgetful, Slowlearner, and
      Scatterbrain. All three have a learning or short-term memory deficit in
      contextual fear conditioning. Forgetful was further characterized and showed a
      highly specific phenotype. The contextual fear-conditioning deficit was apparent
      when Forgetful was trained with tone-shock pairings, but not when trained with
      shock alone. The deficit was not due to changes in shock sensitivity or anxiety.
      Forgetful was not impaired in two other memory tests (hidden platform version of
      Morris water maze and object recognition). Our data show that a mutagenesis
      screen can generate mutant mice with highly specific memory phenotypes that can
      supplement existing mice with targeted mutations. Mapping of Slowlearner found
      linkage to a region of chromosome 12 (LOD score of 6.5 close to D12Mit171), which
      suggests that ENU mutants should enable the positional cloning of genes involved
      in memory formation.

PMID- 16585791
TI  - Dopamine transporter blockade increases LTP in the CA1 region of the rat
      hippocampus via activation of the D3 dopamine receptor.
AB  - Dopamine has been demonstrated to be involved in the modulation of long-term
      potentiation (LTP) in the CA1 region of the hippocampus. As monoamine transporter
      blockade will increase the actions of endogenous monoamine neurotransmitters, the
      effect of a dopamine transporter (DAT) antagonist on LTP was assessed using field
      excitatory postsynaptic potentials recorded in the CA1 region of the rat
      hippocampal slice preparation. Application of the DAT-specific blocker GBR 12,935
      produced a significant enhancement in LTP of Schaffer collateral synapses in the
      CA1 at concentrations as low as 100 nM. A selective D1/D5 dopamine receptor
      antagonist (SCH 23,390, 1 microM) did not affect the ability of GBR 12,935 to
      enhance LTP, whereas application of the D3 dopamine receptor antagonist U 99,194
      (1 microM) blocked the GBR 12,935-induced enhancement in LTP. In addition, a D3
      dopamine receptor agonist (7-OH-DPAT, 1 microM) caused a significant increase in
      LTP, an effect that was also blocked by U 99,194 (3 microM). These results
      suggest that either endogenously released dopamine (facilitated by DAT blockade)
      or exogenously applied dopamine agonist can act to increase LTP in the CA1 of the
      hippocampus via activation of the D3 subtype of dopamine receptor.

PMID- 16585792
TI  - Individual differences in dopamine efflux in nucleus accumbens shell and core
      during instrumental learning.
AB  - Combined activation of dopamine D1- and NMDA-glutamate receptors in the nucleus
      accumbens has been strongly implicated in instrumental learning, the process in
      which an individual learns that a specific action has a wanted outcome. To assess
      dopaminergic activity, we presented rats with two sessions (30 trials each) of a
      one-lever appetitive instrumental task and simultaneously measured dopamine
      efflux in the shell and core accumbens subareas using in vivo microdialysis.
      Dopamine efflux was increased during each session in all areas. The behavioral
      performance of the rats in the second session led us to divide them into a
      learning group (>90% correct trials) and a non-learning group. In the first
      session, the rats of the learning group showed significantly higher increases.
      The difference was most pronounced in the shell. In the second session, the
      dopamine increase was similar in both groups, although the learning groups now
      pressed the lever about three times more often and consequently obtained more
      rewards. We conclude that task-related activation of dopamine efflux is different
      between learning and non-learning rats only during the learning phase. These
      results support the pharmacological evidence that dopamine is of particular
      importance during the instrumental learning process.

PMID- 16585793
TI  - A temporally distinct role for group I and group II metabotropic glutamate
      receptors in object recognition memory.
AB  - Recognition memory, involving the ability to discriminate between a novel and
      familiar object, depends on the integrity of the perirhinal cortex (PRH).
      Glutamate, the main excitatory neurotransmitter in the cortex, is essential for
      many types of memory processes. Of the subtypes of glutamate receptor,
      metabotropic receptors (mGluRs) have received less study than NMDA receptors;
      thus, the reported experiments examined the role of mGluRs in familiarity
      discrimination in the rat PRH. Experiments 1 and 2 assessed the effects of
      systemic administration of MPEP, a group I mGluR (specifically mGluR5)
      antagonist, and/or LY341495, a group II mGluR antagonist, on a spontaneous object
      novelty preference task. Simultaneous antagonism of both group I and II mGluRs
      impaired familiarity discrimination following a 24-h but not a 15-min delay,
      while antagonism of either mGluR subtype alone had no effect at either delay. The
      impairment was in acquisition, as in Experiment 3 coadministration of MPEP and
      LY341495 did not affect recognition memory performance when administered either
      after the sample phase or prior to test. The impairment in long-term recognition
      memory was mediated by mGluRs in the PRH, as localized intracortical antagonism
      of group I and II mGluRs also produced a deficit (Experiment 4). No evidence was
      found for an involvement of group III mGluRs in the acquisition of long-term
      familiarity discrimination (Experiment 5). These findings establish that
      glutamatergic neurotransmission in the PRH via group I and II mGluRs is crucial
      for the acquisition, but not for the consolidation or retrieval of long-term
      object recognition memory.

PMID- 16585794
TI  - Reversible hippocampal lesions disrupt water maze performance during both recent
      and remote memory tests.
AB  - Conventional lesion methods have shown that damage to the rodent hippocampus can
      impair previously acquired spatial memory in tasks such as the water maze. In
      contrast, work with reversible lesion methods using a different spatial task has
      found remote memory to be spared. To determine whether the finding of spared
      remote spatial memory depends on the lesion method, we reversibly inactivated the
      hippocampus with lidocaine either immediately (0-DAY) or 1 mo (30-DAY) after
      training in a water maze. For both the 0-DAY and 30-DAY retention tests, rats
      that received lidocaine infusions exhibited impaired performance. In addition,
      when the 0-DAY group was retested 2 d later, (when the drug was no longer
      active), the effect was reversed. That is, rats that had previously received
      lidocaine performed as well as control rats did. These findings indicate that the
      rodent hippocampus is important for both recent and remote spatial memory, as
      assessed in the water maze. What determines whether remote spatial memory is
      preserved or impaired following disruption of hippocampal function appears to be
      the type of task used to assess spatial memory, not the method used to disrupt
      the hippocampus.

PMID- 16585795
TI  - Simultaneous training on two hippocampus-dependent tasks facilitates acquisition
      of trace eyeblink conditioning.
AB  - A common cellular alteration, reduced post-burst afterhyperpolarization (AHP) in
      CA1 neurons, is associated with acquisition of the hippocampus-dependent tasks
      trace eyeblink conditioning and the Morris water maze. As a similar increase in
      excitability is correlated with these two learning paradigms, we sought to
      determine the interactive behavioral effects of training animals on both tasks by
      using either a consecutive or simultaneous training design. In the consecutive
      design, animals were trained first on either the trace eyeblink conditioning task
      for six sessions, followed by training on the water maze task for six sessions,
      or vice versa. The simultaneous design consisted of six or 11 training days;
      animals received one session/day of both trace eyeblink conditioning and water
      maze training. Separate groups were used for consecutive and simultaneous
      training. Animals trained on both tasks simultaneously were significantly
      facilitated in their ability to acquire the trace eyeblink conditioning task; no
      effect of simultaneous training was seen on the water maze task. No effect was
      seen on acquisition for either task when using the consecutive training design.
      Taken together, these findings provide insight into how the hippocampus processes
      information when animals learn multiple hippocampus-dependent tasks.

PMID- 16585796
TI  - The cerebellum in maintenance of a motor skill: a hierarchy of brain and spinal
      cord plasticity underlies H-reflex conditioning.
AB  - Operant conditioning of the H-reflex, the electrical analog of the spinal stretch
      reflex, is a simple model of skill acquisition and involves plasticity in the
      spinal cord. Previous work showed that the cerebellum is essential for down
      conditioning the H-reflex. This study asks whether the cerebellum is also
      essential for maintaining down-conditioning. After rats decreased the soleus H
      reflex over 50 d in response to the down-conditioning protocol, the cerebellar
      output nuclei dentate and interpositus (DIN) were ablated, and down-conditioning
      continued for 50-100 more days. In naive (i.e., unconditioned) rats, DIN ablation
      itself has no significant long-term effect on H-reflex size. During down
      conditioning prior to DIN ablation, eight Sprague-Dawley rats decreased the H
      reflex to 57% (+/-4 SEM) of control. It rose after ablation, stabilizing within 2
      d at about 75% and remaining there until approximately 40 d after ablation. It
      then rose to approximately 130%, where it remained through the end of study 100 d
      after ablation. Thus, DIN ablation in down-conditioned rats caused an immediate
      increase and a delayed increase in the H-reflex. The final result was an H-reflex
      significantly larger than that prior to down-conditioning. Combined with previous
      work, these remarkable results suggest that the spinal cord plasticity directly
      responsible for down-conditioning, which survives only 5-10 d on its own, is
      maintained by supraspinal plasticity that survives approximately 40 d after loss
      of cerebellar output. Thus, H-reflex conditioning seems to depend on a hierarchy
      of brain and spinal cord plasticity to which the cerebellum makes an essential
      contribution.

PMID- 16585797
TI  - Different mechanisms of fear extinction dependent on length of time since fear
      acquisition.
AB  - Fear extinction is defined as a decline in conditioned fear responses (CRs)
      following nonreinforced exposure to a feared conditioned stimulus (CS).
      Behavioral evidence indicates that extinction is a form of inhibitory learning:
      Extinguished fear responses reappear with the passage of time (spontaneous
      recovery), a shift of context (renewal), and unsignaled presentations of the
      unconditioned stimulus (reinstatement). However, there also is evidence to
      suggest that extinction is an "unlearning" process corresponding to
      depotentiation of potentiated synapses within the amygdala. Because
      depotentiation is induced more readily at short intervals following LTP induction
      and is not inducible at all at a sufficient delay, it may be that extinction
      initiated shortly following fear acquisition preferentially engages
      depotentiation/"unlearning," whereas extinction initiated at longer delays
      recruits a different mechanism. We investigated this possibility through a series
      of behavioral experiments examining the recoverability of conditioned fear
      following extinction. Consistent with an inhibitory learning mechanism of
      extinction, rats extinguished 24-72 h following acquisition exhibited moderate to
      strong reinstatement, renewal, and spontaneous recovery. In contrast, and
      consistent with an erasure mechanism, rats extinguished 10 min to 1 h after
      acquisition exhibited little or no reinstatement, renewal, or spontaneous
      recovery. These data support a model in which different neural mechanisms are
      recruited depending on the temporal delay of fear extinction.

PMID- 16585798
TI  - Latent memory for sensitization in Aplysia.
AB  - In the analysis of memory it is commonly observed that, even after a memory is
      apparently forgotten, its latent presence can still be revealed in a subsequent
      learning task. Although well established on a behavioral level, the mechanisms
      underlying latent memory are not well understood. To begin to explore these
      mechanisms, we have used Aplysia, a model system that permits the simultaneous
      study of memory at the behavioral, cellular, and molecular levels. We first
      demonstrate that robust latent memory is induced by long-term sensitization
      training of the tail-elicited siphon withdrawal reflex. It is revealed by its
      ability to facilitate the subsequent induction of three mechanistically distinct
      temporal domains of sensitization memory: short-term, intermediate-term, and long
      term memory. Under our training conditions, the latent memory persists for at
      least 2 d following the decay of original memory expression but appears to be
      gone by 4 d. Interestingly, we also find that latent memory is induced even in
      the absence of overt memory for the original training. These findings now permit
      the analysis of the cellular and molecular architecture of a common feature of
      learning and memory.

PMID- 16585799
TI  - The effect of music on cognitive performance: insight from neurobiological and
      animal studies.
AB  - The past 50 years have seen numerous claims that music exposure enhances human
      cognitive performance. Critical evaluation of studies across a variety of
      contexts, however, reveals important methodological weaknesses. The current
      article argues that an interdisciplinary approach is required to advance this
      research. A case is made for the use of appropriate animal models to avoid many
      confounds associated with human music research. Although such research has
      validity limitations for humans, reductionist methodology enables a more
      controlled exploration of music's elementary effects. This article also explores
      candidate mechanisms for this putative effect. A review of neurobiological
      evidence from human and comparative animal studies confirms that musical stimuli
      modify autonomic and neurochemical arousal indices, and may also modify synaptic
      plasticity. It is proposed that understanding how music affects animals provides
      a valuable conjunct to human research and may be vital in uncovering how music
      might be used to enhance cognitive performance.

PMID- 16585800
TI  - The endophenotype of impulsivity: reaching consilience through behavioral,
      genetic, and neuroimaging approaches.
AB  - Impulsivity is a multidimensional construct with implications for understanding
      the etiology and treatment of multiple forms of psychopathology. As a
      multidimensional construct, however, the processes underlying impulsivity,
      particularly behavioral inhibition, must be separated to allow for investigations
      into its neurogenetic bases. Evidence from both animal and human studies supports
      the role of dopamine in impulsivity, and neuroimaging research is elucidating
      brain regions involved in behavioral inhibition. Evidence is now emerging that
      suggests an interaction between dopamine system genes and frontal brain regions
      in underlying individual differences in behavioral inhibition. However, to reach
      a comprehensive understanding of the neurogenetic bases of behavioral inhibition,
      an appropriate framework is required. Therefore, it is proposed that by
      identifying intervening variables more sensitive to the effects of genetic
      variation, known as an endophenotype approach, we will be able to overcome many
      of the methodological limitations that prevent a better understanding at present.

PMID- 16585804
TI  - "It's Only a Survey!".

PMID- 16585805
TI  - The meaning of living with spinal cord injury 5 to 10 years after the injury.
AB  - A phenomenological study was conducted with 20 spinal cord injured persons and
      their family members to examine the meaning of living with spinal cord injury 5
      to 10 years after the initial injury. Seven themes emerged from the data. The
      themes are looking for understanding to a life that is unknown, stumbling along
      an unlit path, viewing self through a stained glass window, challenging the bonds
      of love, being chained to the injury, moving forward in a new way of life, and
      reaching normalcy. The uncovered meanings enhance our understanding and
      appreciation that living with spinal cord injury is a continuous learning
      experience. The study findings may be useful in the development of self-care
      strategies and ongoing interventions that focus on maintaining physical and
      psychological health for both spinal cord injured persons and their family
      members throughout the course of living with the disability.

PMID- 16585801
TI  - Relational spatial reasoning by a nonhuman: the example of capuchin monkeys.
AB  - The authors review spontaneous manipulation and spatial problem solving by
      capuchin monkeys to illuminate the nature of relational reasoning (wherein two or
      more elements of a problem or situation are considered together to arrive at a
      course of action) that these monkeys use in goal-directed activity. Capuchin
      monkeys master problems with one, two, or three spatial relations, and if more
      than one relation, at least two relations may be managed concurrently. They can
      master static and dynamic relations and, with sufficient practice, can produce
      specific spatial relations through both direct and distal action. Examining
      capuchins' spatial problem-solving behavior with objects in the framework of a
      spatial relational reasoning model leads to new interpretations of previous
      studies with these monkeys and other nonhuman animals. The model produces a
      variety of testable predictions concerning the contribution of relational
      properties to spatial reasoning. It also provides conceptual linkages with
      neurological processes and cognitive analyses of physical reasoning.
      Understanding relational spatial reasoning, including tool use, in a wider view
      is vital to informed, principled comparison of problem solving and the use of
      technology across species, across ages within species, and across eras in human
      prehistory.

PMID- 16585806
TI  - MDS coordinator relationships and nursing home care processes.
AB  - This study describes how Minimum Data Set (MDS) coordinators' relationship
      patterns influence nursing home care processes. MDS coordinators interact with
      nursing home staff to coordinate resident assessment and care planning, but
      little is known about how they enact this role or influence particular care
      processes beyond paper compliance. Guided by complexity science and using two
      nursing home case studies, the authors describe MDS coordinators' relationship
      patterns by assessing the extent to which they used and fostered good
      connections, new information flow, and cognitive diversity. MDS coordinators at
      one site fostered new information flow, good connections, and cognitive
      diversity, which positively influenced assessment and care planning, whereas
      those at the other site did little to foster these three relationship parameters,
      with little influence on care processes. This study revealed that MDS
      coordinators are an important new source of capacity for the nursing home
      industry to improve quality of care.

PMID- 16585807
TI  - Challenges and strategies of instrument translation.
AB  - The often-cited back translation procedure used for the translation of research
      instruments has not been consistently described in cross-cultural literature.
      Translation errors resulting in conceptually dissimilar instruments can
      compromise comparisons of cross-cultural health initiatives. This report
      describes a five-step translation procedure and equivalence and reliability
      testing process used to develop the High School Questionnaire: Profile of
      Experiences (HSQ) in Mandarin. Each step of the translation process provided
      additional information and detected discrepancies between the English and
      Mandarin versions of the HSQ. Issues related to grammatical translation, cultural
      usage and experience, syntax, and concept interpretation were exposed by the
      translation process. The procedures used in this 18-month study were rigorous
      enough to create an instrument that was both linguistically appropriate and
      culturally relevant.

PMID- 16585809
TI  - Development of the purposeful action medication-taking questionnaire.
AB  - This three-phase study describes the development and psychometric properties of
      the Medication-Taking Questionnaire (MTQ) to measure the purposeful action domain
      (reasons individuals decide to accept medication treatment) in the medication
      adherence model for hypertension. During Phase I, items were evaluated for
      content validity and clarity. Item analysis, internal consistency, and
      exploratory factor analysis were preformed during Phase II to finalize the MTQ:
      Purposeful Action as 12 items and 2 subscales (treatment benefits and medication
      safety). Phase III evaluated the MTQ: Purposeful Action for temporal stability
      and construct validity. The final version MTQ: Purposeful Action demonstrated
      good internal consistency, temporal stability, and construct validity. The MTQ:
      Purposeful Action appears to have good psychometric characteristics that
      represent the decision-making process for adherence in medication treatment for
      hypertension.

PMID- 16585808
TI  - Survey response inducements for registered nurses.
AB  - The past 20 years have seen an overall decline in survey response rates and an
      even more pronounced decline in samples of health care professionals. The authors
      tested the use of a "thank you" or "reminder" postcard as a method by which to
      stem the tide of declining response rates. The authors conducted a mail and
      telephone survey of 49,605 registered nurses for the 2000 National Sample Survey
      of Registered Nurses and sent an extra mailing to a random subsample (n = 4,968).
      They then compared response rates for both groups. Contrary to prior research,
      this study found that reminder postcards did not improve response rates or rates
      of return. There may be several reasons for this finding, including the general
      familiarity with, and high saliency of, this research project for the nursing
      community. These results suggest that even widely accepted best practices for
      survey methods deserve scrutiny when applied to special subpopulations.

PMID- 16585810
TI  - Response to "The long-term phenomena of women's postabortion experiences".

PMID- 16585811
TI  - Outpatient treatment of community-acquired pneumonia: evolving trends and a focus
      on fluoroquinolones.
AB  - BACKGROUND: Increasing use of broad-spectrum antibiotics in the community,
      including fluoroquinolones, has been reported, despite concerns for developing
      antibiotic resistant organisms. Community-acquired pneumonia (CAP) is commonly
      treated on an outpatient basis, and recent treatment guidelines suggest only a
      limited role for fluoroquinolones. OBJECTIVES: To identify evolving trends in the
      outpatient treatment of CAP in adults, and to identify factors associated with
      receipt of a fluoroquinolone. METHODS: Retrospective observational design using
      population-based administrative data. Initial outpatient treatment for subjects
      diagnosed with CAP between May 1996 and March 2002 was examined. Logistic
      regression was used to examine the influence of patient characteristics on the
      receipt of a fluoroquinolone. RESULTS: A total of 31,940 outpatients with CAP
      were identified. The proportion of patients receiving fluoroquinolones increased
      from 6.6% in 1996/97 to 25.2% in 2001/02. Over the course of the study, 158
      (25.9%) of the 610 patients meeting the eligibility criteria for treatment with
      fluoroquinolones, according to treatment guidelines, received these agents. Of
      the 31,330 subjects who did not meet the eligibility criterion, 3,886 (12.4%)
      received a fluoroquinolone. Other variables that influenced the receipt of a
      fluoroquinolone included: age (for every 10-year increase) [OR=1.16 (1.14-1.19)],
      urban residence [OR=1.40 (1.30-1.51)], presentation to an emergency department
      [OR=0.80 (0.70-0.90)], high-level drug use (six or more different drugs in the
      previous year) [OR=1.50 (1.41-1.59)], and income-level (highest to lowest)
      [OR=1.20 (1.08-1.35)]. CONCLUSION: The use of fluoroquinolones for the treatment
      of CAP is increasing. However less than 4% of the subjects receiving
      fluoroquinolones met eligibility requirements according to treatment guidelines.
      Initiatives to increase the uptake of treatment guidelines appear warranted.

PMID- 16585812
TI  - Anti-diabetic drug use and the risk of motor vehicle crash in the elderly.
AB  - BACKGROUND: Studies of the risk of motor vehicle crash associated with diabetes
      have produced conflicting results. OBJECTIVES: To assess whether the use of anti
      diabetic drugs among the elderly increases the risk of motor vehicle crash.
      METHODS: The computerized databases of the various universal insurance programs
      of Quebec were linked to form a cohort of all 224,734 elderly drivers that was
      followed from 1990-1993. Using a nested case-control approach, all 5,579 drivers
      involved in an injurious crash (cases) and a random sample of 13,300 control
      subjects were identified. Exposure to anti-diabetic drugs was assessed in the
      year preceding the index date, namely the date of the crash for the cases and a
      randomly selected date during follow-up for the controls. RESULTS: The adjusted
      rate ratio of an injurious crash was 1.4 (95% CI: 1.0-2.0) for current users of
      insulin monotherapy relative to non-users and 1.3 (95% CI: 1.0-1.7) for
      sulfonylurea and metformin combined. Monotherapy, using either a sulfonylurea or
      metformin, was not associated with an increased risk. There was a dose-response
      effect in subjects using high doses of combined oral therapy (RR 1.4; 95% CI: 1.0
      2.0). For users of insulin monotherapy or of high doses of combined oral therapy,
      the increase corresponds to an excess rate of 32 crashes per 10,000 elderly
      drivers per year. CONCLUSIONS: L Elderly drivers treated with insulin monotherapy
      or a combination of sulfonylurea and metformin, especially at high doses, have a
      small increased risk of injurious crashes. There is no increased risk associated
      with any regimen of oral monotherapy.

PMID- 16585813
TI  - What can we learn from functional neuroimaging in children?

PMID- 16585815
TI  - Incidence of periventricular leucomalacia among a cohort of very low birth weight
      neonates(< 1500 g).
AB  - BACKGROUND: Periventricular leucomalacia (PVL) is the most important
      neuropathologic lesion underlying major neuro-motor deficits of pre-term very low
      birth weight (VLBW) infants. Published data regarding PVL is not available from
      our country. OBJECTIVES: A study was planned with main objectives to estimate
      incidence and describe natural history of PVL among a very low birth weight
      cohort. STUDY DESIGN: A cohort study was performed on inborn VLBW babies over one
      year period at a tertiary neonatal intensive care unit. Serial weekly cranial
      ultrasounds were performed on 97 enrolled subjects until discharge, to diagnose
      and describe natural history of PVL. RESULTS: 31 out of 97 enrolled subjects
      developed PVL. No case of PVL developed beyond 19 days of postnatal life. Serial
      ultrasounds for each baby were tracked until discharge or death. Majority of
      lesions at onset were flares. Cysts tended to develop in over one third of cases
      during course of hospital stay. About 50% of ultrasound had normalized at
      discharge and sequelae such as cerebral atrophy and ventriculomegaly had appeared
      in few, the rest of lesions being either flares or cysts of PVL. CONCLUSIONS: PVL
      is fairly common among very low birth weight neonates. Ultrasonographic lesions
      of PVL undergo dynamic evolution from time of first detection to either progress,
      regress or leave sequelae before discharge. Ultrasound remains an important
      bedside diagnostic tool for PVL.

PMID- 16585816
TI  - Deleterious functional impact of anemia on young adolescent school girls.
AB  - Iron deficiency anemia during adolescence may reduce physical work capacity and
      cognitive function. OBJECTIVES: To assess the physical work capacity and
      cognition of underprivileged anemic schoolgirls in Vadodara in early adolescence
      as compared to their non-anemic counterparts. DESIGN: Prior to initiating anemia
      control interventions, schoolgirls in early adolescence were studied with regard
      to their hemoglobin status, physical work capacity and cognitive functions.
      SETTING: Schoolgirls from four municipal primary schools in the age of 9 - 14
      years were studied. METHODS: In four Primary Municipal schools, hemoglobin of
      subjects was assessed using standard methods; physical work capacity using
      Modified Harvards Step test and cognitive functions using selected tests from the
      modified Wechsler Intelligence Scale for Children (WISC), suitably adapted for
      this group (n = 230). RESULTS: The mean hemoglobin was 11.32 g/dL, and anemia
      prevalence: 67%. A higher number of steps were climbed and a shorter time was
      taken to revert to the basal pulse rate (recovery time) by non-anemic girls
      compared to anemic girls (P < 0.001). Significantly lower scores in digit span
      and visual memory test were seen in anemic compared to non-anemic girls. The
      adverse impact of anemia remained after controlling for undernutrition (BMI).
      CONCLUSION: Anemia is likely to adversely affect physical work capacity and
      cognition in young adolescent girls undergoing pubertal development. Further
      research should be conducted in both school and community based settings to cover
      non-school going children.

PMID- 16585817
TI  - Neurocysticercosis: management issues.

PMID- 16585818
TI  - Growth hormone in turner syndrome.
AB  - We assessed the effect of one year of therapy with recombinant Human Growth
      Hormone (rhGH) on growth velocity of 16 Indian girls with Turner Syndrome (TS) in
      a prospective, open trial. Patients received rhGH in a dose of 1 IU (0.3
      mg)/kg/week. The mean pretreatment height was 117.1 cms (Z score minus 3.4),
      height velocity was 3.8 cm per year (Z score minus 2.4), and predicted height was
      140 cm. At the end of therapy mean height was 123.9 (Z score minus 3.1), height
      velocity was 6.7 cm per year (Z score + 1.7), and the predicted height was 142.4
      cm. The increment in height velocity with growth hormone therapy was
      statistically significant (P value = 0.001) and the mean increment in predicted
      height was 2.4 cm. Our study shows that girls with TS in India benefit from
      therapy with rhGH.

PMID- 16585819
TI  - Cerebral blood flow abnormalities in children with Sydenham's chorea: a SPECT
      study.
AB  - Functional imaging studies in patients with Sydenhams chorea have suggested brain
      perfusional abnormalities. In this study, we aimed to investigate the cerebral
      perfusion patterns of the cortical/subcortical structures by using Tc-99m
      hexamethylpropylenamine oxime single photon emission computed tomography in
      children with Sydenhams chorea, accompanied with magnetic resonance imaging and
      cranial Doppler studies. Brain MRI and Doppler studies of the all cases were
      normal. In the brain SPECT study, six patients were determined to have cerebral
      perfusion abnormalities. Although six patients responded well to the therapy, two
      girls who had hypoperfusion in the right frontal region as well as hypo- /
      hyperperfusion in the basal ganglia did not respond to therapy. While the chorea
      form of the patients who have cerebral perfusional abnormality was generalized,
      the clinical picture of the patients with normal cerebral perfusion was in the
      form of hemichorea.

PMID- 16585820
TI  - Hypocalcemia due to vitamin D deficiency in exclusively breastfed infants.
AB  - This report is based on observations during the conduct of a study of
      hypocalcemia in infants and children. In a study of 50 cases, 13 exclusively
      breast fed infants manifesting with hypocalcemic seizures were confirmed to have
      vitamin D deficiency. None of the 13 infants had received vitamin D
      supplementation. All of them had biochemical evidence of hyperparathyroidism and
      low levels of 25 (OH) Vit D3 and promptly responded to therapy with vitamin D and
      calcium. All the mothers of these 13 infants had low levels of 25 (OH) Vit D3.
      Mothers of 5 infants had reported reduced exposure to sunlight due to religious
      reasons. This report emphasizes the need to supplement Vitamin D in exclusively
      breast fed infants and also to encourage exposure to sunlight in them and their
      mothers.

PMID- 16585821
TI  - Safe and painless manipulation of penile zipper entrapment.
AB  - Entrapment of prepuce in a zipper is a common cause of prepuceal injury in
      children. The reported interventions include dismantling the zipper with bone or
      wire cutters, to circumcision. A quick, simple and non-traumatic approach to the
      zipper manipulation is presented in which prepuce is instantly released by
      lateral compression of the zip fastener, using a pliers.

PMID- 16585823
TI  - Ring chromosome 13 in an infant with ambiguous genitalia.
AB  - Ring chromosome is a rare chromosomal abnormality. We report a case of ring
      chromosome 13 associated with ambiguous genitalia. Karyotype is the important
      investigation in the evaluation of a case with ambiguous genitalia and
      chromosomal analysis should not be limited to only presence of X and Y
      chromosomes.

PMID- 16585822
TI  - Peripheral gangrene: an uncommon manifestation of disseminated tuberculosis.
AB  - Peripheral gangrene as a manifestation of tuberculosis is very uncommon. An 8
      year old male child presented with non-healing ulcer over the sole of left foot,
      left inguinal tubercular lymphadenopathy with scrofloderma, tubercular pleural
      effusion and gangrene of the right fore foot. The child improved on
      antitubercular treatment.

PMID- 16585824
TI  - Encephalocraniocutaneous lipomatosis.

PMID- 16585825
TI  - Uncommon manifestations of Klippel Feil syndrome.

PMID- 16585826
TI  - Torsion of vermiform appendix.

PMID- 16585827
TI  - Post intra ventricular hemorrhage neonatal cranial diabetes insipidus.

PMID- 16585828
TI  - Recurrent meningitis in a family with C3 deficiency.

PMID- 16585829
TI  - Role of DMSA in pediatric UTI.

PMID- 16585830
TI  - IAP drug formulary 2004.

PMID- 16585831
TI  - DOTS in pediatric tuberculosis.

PMID- 16585833
TI  - Comments on 'The effect of logarithmic compression on the estimation of the
      Nakagami parameter for ultrasonic tissue characterization'.
AB  - In a recently published paper (Tsui et al 2005 Phys. Med. Biol. 50 3235-44), the
      authors demonstrated estimation of the Nakagami parameter of the logcompressed
      envelopes and the application of such an approach in ultrasonic tissue
      characterization. The comments in this letter suggest that the authors ignored
      some important statistical properties of logcompressed data leading to serious
      errors in their studies and results.

PMID- 16585836
TI  - Varying MLC end projection size: an effect of the double-focused Siemens
      multileaf collimator.
AB  - Siemens linacs use multileaf collimators (MLCs) that move in an arc such that the
      flat faces of the leaf ends are always in the same plane as the radiation focus.
      An effect of this is that the magnification of the leaf end projection at the
      isocentric plane normal to the collimator rotation axis varies with the drive
      position of the leaves. This effect is quantified theoretically and empirically
      verified. A method is introduced for assessing the importance of the effect for a
      particular MLC pattern. The significance of the effect is discussed.

PMID- 16585835
TI  - Scattered dose to thyroid from prophylactic cranial irradiation during childhood:
      a Monte Carlo study.
AB  - The purpose of this study was to estimate the scattered dose to thyroid from
      prophylactic cranial irradiation during childhood. The MCNP transport code and
      mathematical phantoms representing the average individual at ages 3, 5, 10, 15
      and 18 years old were employed to simulate cranial radiotherapy using two lateral
      opposed fields. The mean radiation dose received by the thyroid gland was
      calculated. A 10 cm thick lead block placed on the patient's couch to shield the
      thyroid was simulated by MCNP code. The Monte Carlo model was validated by
      measuring the scattered dose to the unshielded and shielded thyroid using three
      different humanoid phantoms and thermoluminescense dosimetry. For a cranial dose
      of 18 Gy, the thyroid dose obtained by Monte Carlo calculations varied from 47 to
      79 cGy depending upon the age of the child. Appropriate placement of the couch
      block resulted in a thyroid dose reduction by 39 to 54%. Thyroid dose values at
      all possible positions of the radiosensitive gland with respect to the inferior
      field edge at five different patient ages were found. The mean difference between
      Monte Carlo results and thyroid dose measurements was 9.6%.

PMID- 16585837
TI  - RadSim: a program to simulate individual particle interactions for educational
      purposes.
AB  - A program was developed, RadSim, which can be used to simulate certain individual
      interactions of photons, electrons, positrons and alpha particles with a single
      atom for educational purposes. The program can be run in two modes: manual and
      simulated. In the manual mode, an individual particle undergoing a specified
      interaction with a target atom can be simulated, which essentially comes down to
      a graphical evaluation of kinematic equations. In the simulated mode, a preset
      number of identical particles are allowed to undergo a specified interaction type
      with a target atom. The exit channel of the interaction is sampled from
      probability distributions using Monte Carlo methods. The incoming and outgoing
      particles are visualized and the frequency distribution of the kinematic
      variables of the exit channel is displayed graphically. It has to be emphasized
      that RadSim was mainly developed for educational purposes.

PMID- 16585838
TI  - MRI temperature mapping during thermal balloon angioplasty.
AB  - Knowledge on the thermal dose delivered during thermal balloon angioplasty (TBA)
      is desirable to understand why TBA's outcome varies widely among patients and why
      it is subject to high restenosis rates. In its conventional implementation, TBA
      involves injection of a heated medium into a balloon positioned within a stenotic
      blood vessel. The medium injection causes flow, motion and susceptibility
      redistribution artefacts that are devastating to the proton resonance frequency
      shift (PRFS) technique of MRI temperature mapping. Here, we propose to separate
      in time medium injection and heating by first inflating a balloon with a medium
      at an initial temperature, and then by heating the medium up using laser light.
      The separation is shown to eliminate all the mentioned artefacts and to enable
      real-time MRI temperature mapping using the PRFS technique. Accurate and reliable
      temperature maps were acquired in a TBA balloon itself and in the surrounding
      phantom tissue during heat application.

PMID- 16585839
TI  - Rapid calculation of biological effects in ion radiotherapy.
AB  - We describe a method for fast calculation of biological effects after ion
      irradiation. It is an alternative derivative of the established local effect
      model (LEM) and has been integrated into GSI's TRiP98 treatment planning system.
      We show that deviations from our classic approach for treatment planning are less
      than 5% for therapeutical doses, but calculational speed can be improved by one
      to two orders of magnitude. This will allow sophisticated methods of treatment
      planning for ion irradiation, taking biological effects fully into account.

PMID- 16585840
TI  - Classification of movement intention by spatially filtered electromagnetic
      inverse solutions.
AB  - We couple standardized low-resolution electromagnetic tomography, an inverse
      solution for electroencephalography (EEG) and the common spatial pattern, which
      is here conceived as a data-driven beamformer, to classify the benchmark BCI
      (brain-computer interface) competition 2003, data set IV. The data set is from an
      experiment where a subject performed a self-paced left and right finger tapping
      task. Available for analysis are 314 training trials whereas 100 unlabelled test
      trials have to be classified. The EEG data from 28 electrodes comprise the
      recording of the 500 ms before the actual finger movements, hence represent
      uniquely the left and right finger movement intention. Despite our use of an
      untrained classifier, and our extraction of only one attribute per class, our
      method yields accuracy similar to the winners of the competition for this data
      set. The distinct advantages of the approach presented here are the use of an
      untrained classifier and the processing speed, which make the method suitable for
      actual BCI applications. The proposed method is favourable over existing
      classification methods based on an EEG inverse solution, which rely either on
      iterative algorithms for single-trial independent component analysis or on
      trained classifiers.

PMID- 16585841
TI  - A filtering approach based on Gaussian-powerlaw convolutions for local PET
      verification of proton radiotherapy.
AB  - Because proton beams activate positron emitters in patients, positron emission
      tomography (PET) has the potential to play a unique role in the in vivo
      verification of proton radiotherapy. Unfortunately, the PET image is not directly
      proportional to the delivered radiation dose distribution. Current treatment
      verification strategies using PET therefore compare the actual PET image with
      full-blown Monte Carlo simulations of the PET signal. In this paper, we describe
      a simpler and more direct way to reconstruct the expected PET signal from the
      local radiation dose distribution near the distal fall-off region, which is
      calculated by the treatment planning programme. Under reasonable assumptions, the
      PET image can be described as a convolution of the dose distribution with a
      filter function. We develop a formalism to derive the filter function
      analytically. The main concept is the introduction of 'Q' functions defined as
      the convolution of a Gaussian with a powerlaw function. Special Q functions are
      the Gaussian itself and the error function. The convolution of two Q functions is
      another Q function. By fitting elementary dose distributions and their
      corresponding PET signals with Q functions, we derive the Q function
      approximation of the filter. The new filtering method has been validated through
      comparisons with Monte Carlo calculations and, in one case, with measured data.
      While the basic concept is developed under idealized conditions assuming that the
      absorbing medium is homogeneous near the distal fall-off region, a generalization
      to inhomogeneous situations is also described. As a result, the method can
      determine the distal fall-off region of the PET signal, and consequently the
      range of the proton beam, with millimetre accuracy. Quantification of the
      produced activity is possible. In conclusion, the PET activity resulting from a
      proton beam treatment can be determined by locally filtering the dose
      distribution as obtained from the treatment planning system. The filter function
      can be calculated analytically using convolutions of Gaussians and powerlaw
      functions.

PMID- 16585842
TI  - In vitro determination of normal and neoplastic human brain tissue optical
      properties using inverse adding-doubling.
AB  - To complement a project towards the development of real-time optical biopsy for
      brain tissue discrimination and surgical resection guidance, the optical
      properties of various brain tissues were measured in vitro and correlated to
      features within clinical diffuse reflectance tissue spectra measured in vivo.
      Reflectance and transmission spectra of in vitro brain tissue samples were
      measured with a single-integrating-sphere spectrometer for wavelengths 400-1300
      nm and converted to absorption and reduced scattering spectra using an inverse
      adding-doubling technique. Optical property spectra were classified as deriving
      from white matter, grey matter or glioma tissue according to histopathologic
      diagnosis, and mean absorption and reduced scattering spectra were calculated for
      the three tissue categories. Absolute reduced scattering and absorption values
      and their relative differences between histopathological groups agreed with
      previously reported results with the exception that absorption coefficients were
      often overestimated, most likely due to biologic variability or unaccounted light
      loss during reflectance/transmission measurement. Absorption spectra for the
      three tissue classes were dominated by haemoglobin absorption below 600 nm and
      water absorption above 900 nm and generally determined the shape of corresponding
      clinical diffuse reflectance spectra. Reduced scattering spectral shapes followed
      the power curve predicted by the Rayleigh limit of Mie scattering theory. While
      tissue absorption governed the shape of clinical diffuse reflectance spectra,
      reduced scattering determined their relative emission intensities between the
      three tissue categories.

PMID- 16585843
TI  - A hyperspectral fluorescence system for 3D in vivo optical imaging.
AB  - In vivo optical instruments designed for small animal imaging generally measure
      the integrated light intensity across a broad band of wavelengths, or make
      measurements at a small number of selected wavelengths, and primarily use any
      spectral information to characterize and remove autofluorescence. We have
      developed a flexible hyperspectral imaging instrument to explore the use of
      spectral information to determine the 3D source location for in vivo fluorescence
      imaging applications. We hypothesize that the spectral distribution of the
      emitted fluorescence signal can be used to provide additional information to 3D
      reconstruction algorithms being developed for optical tomography. To test this
      hypothesis, we have designed and built an in vivo hyperspectral imaging system,
      which can acquire data from 400 to 1000 nm with 3 nm spectral resolution and
      which is flexible enough to allow the testing of a wide range of illumination and
      detection geometries. It also has the capability to generate a surface contour
      map of the animal for input into the reconstruction process. In this paper, we
      present the design of the system, demonstrate the depth dependence of the
      spectral signal in phantoms and show the ability to reconstruct 3D source
      locations using the spectral data in a simple phantom. We also characterize the
      basic performance of the imaging system.

PMID- 16585845
TI  - Focusing optics of a parallel beam CCD optical tomography apparatus for 3D
      radiation gel dosimetry.
AB  - Optical tomography of gel dosimeters is a promising and cost-effective avenue for
      quality control of radiotherapy treatments such as intensity-modulated
      radiotherapy (IMRT). Systems based on a laser coupled to a photodiode have so far
      shown the best results within the context of optical scanning of radiosensitive
      gels, but are very slow ( approximately 9 min per slice) and poorly suited to
      measurements that require many slices. Here, we describe a fast, three
      dimensional (3D) optical computed tomography (optical-CT) apparatus, based on a
      broad, collimated beam, obtained from a high power LED and detected by a charged
      coupled detector (CCD). The main advantages of such a system are (i) an
      acquisition speed approximately two orders of magnitude higher than a laser-based
      system when 3D data are required, and (ii) a greater simplicity of design. This
      paper advances our previous work by introducing a new design of focusing optics,
      which take information from a suitably positioned focal plane and project an
      image onto the CCD. An analysis of the ray optics is presented, which explains
      the roles of telecentricity, focusing, acceptance angle and depth-of-field (DOF)
      in the formation of projections. A discussion of the approximation involved in
      measuring the line integrals required for filtered backprojection reconstruction
      is given. Experimental results demonstrate (i) the effect on projections of
      changing the position of the focal plane of the apparatus, (ii) how to measure
      the acceptance angle of the optics, and (iii) the ability of the new scanner to
      image both absorbing and scattering gel phantoms. The quality of reconstructed
      images is very promising and suggests that the new apparatus may be useful in a
      clinical setting for fast and accurate 3D dosimetry.

PMID- 16585844
TI  - Effect of optical property estimation accuracy on tomographic bioluminescence
      imaging: simulation of a combined optical-PET (OPET) system.
AB  - Inevitable discrepancies between the mouse tissue optical properties assumed by
      an experimenter and the actual physiological values may affect the tomographic
      localization of bioluminescent sources. In a previous work, the simplifying
      assumption of optically homogeneous tissues led to inaccurate localization of
      deep sources. Improved results may be obtained if a mouse anatomical map is
      provided by a high-resolution imaging modality and optical properties are
      assigned to segmented tissues. In this work, the feasibility of this approach was
      explored by simulating the effect of different magnitude optical property errors
      on the image formation process of a combined optical-PET system. Some comparisons
      were made with corresponding simulations using higher spatial resolution data
      that are typically attainable by CCD cameras. In addition, simulation results
      provided insights on some of the experimental conditions that could lead to poor
      localization of bioluminescent sources. They also provided a rough guide on how
      accurately tissue optical properties need to be known in order to achieve correct
      localization of point sources with increasing tissue depth under low background
      noise conditions.

PMID- 16585846
TI  - Ambient dose equivalent and effective dose from scattered x-ray spectra in
      mammography for Mo/Mo, Mo/Rh and W/Rh anode/filter combinations.
AB  - In this study, scattered x-ray distributions were produced by irradiating a
      tissue equivalent phantom under clinical mammographic conditions by using Mo/Mo,
      Mo/Rh and W/Rh anode/filter combinations, for 25 and 30 kV tube voltages. Energy
      spectra of the scattered x-rays have been measured with a Cd(0.9)Zn(0.1)Te (CZT)
      detector for scattering angles between 30 degrees and 165 degrees . Measurement
      and correction processes have been evaluated through the comparison between the
      values of the half-value layer (HVL) and air kerma calculated from the corrected
      spectra and measured with an ionization chamber in a nonclinical x-ray system
      with a W/Mo anode/filter combination. The shape of the corrected x-ray spectra
      measured in the nonclinical system was also compared with those calculated using
      semi-empirical models published in the literature. Scattered x-ray spectra
      measured in the clinical x-ray system have been characterized through the
      calculation of HVL and mean photon energy. Values of the air kerma, ambient dose
      equivalent and effective dose have been evaluated through the corrected x-ray
      spectra. Mean conversion coefficients relating the air kerma to the ambient dose
      equivalent and to the effective dose from the scattered beams for Mo/Mo, Mo/Rh
      and W/Rh anode/filter combinations were also evaluated. Results show that for the
      scattered radiation beams the ambient dose equivalent provides an overestimate of
      the effective dose by a factor of about 5 in the mammography energy range. These
      results can be used in the control of the dose limits around a clinical unit and
      in the calculation of more realistic protective shielding barriers in
      mammography.

PMID- 16585847
TI  - Analysis and design of a coupled coaxial line TEM resonator for magnetic
      resonance imaging.
AB  - In this paper, we have successfully realized a numerical tool to analyse and to
      design an n-element unloaded coaxial line transverse electromagnetic (TEM)
      resonator. This numerical tool allows the determination of the primary
      parameters, matrices [L], [C] and [R], and simulates the frequency response of
      S11 at the RF port of the designed TEM resonator. The frequency response permits
      evaluation of the unloaded quality factor Q0. As an application, we present the
      analysis and the design of an eight-element unloaded TEM resonator for animal
      studies at 4.7 T. The simulated performance has a -62.81 dB minimum reflection
      and a quality factor of 260 around 200 MHz.

PMID- 16585848
TI  - Polymer gel dosimetry for the TG-43 dosimetric characterization of a new 125I
      interstitial brachytherapy seed.
AB  - In this work, a polymer gel-magnetic resonance (MR) imaging method is employed
      for the dosimetric characterization of a new 125I low dose rate seed (IsoSeed
      model I25.S17). Two vials filled with PABIG gel were prepared in-house and one
      new seed as well as one commercially available 125I seed of similar dose rate and
      well-known dosimetric parameters (IsoSeed model I25.S06) were positioned in each
      vial. Both seeds in each vial were MR scanned simultaneously on days 11 and 26
      after implantation. The data obtained from the known seed in each vial are used
      to calibrate the gel dose response which, for the prolonged irradiation duration
      necessitated by the investigated dose rates, depends on the overall irradiation
      time. Data for this study are presented according to the AAPM TG-43 dosimetric
      formalism. Polymer gel results concerning the new seed are compared to
      corresponding, published dosimetric results obtained, for the purpose of the new
      seed clinical implementation, by our group using the established methods of Monte
      Carlo (MC) simulation and thermo-luminescence dosimetry (TLD). Polymer gel
      dosimetry yields an average dose rate constant value of lambda = (0.921 +/-
      0.031) cGy h(-1) U(-1) relative to (MC)lambda = (0.929 +/- 0.014) cGy h(-1) U(
      1), (TLD)lambda = (0.951 +/- 0.044) cGy h(-1) U(-1) and the average value of
      Lambda = (0.940 +/- 0.051) cGy h(-1) U(-1) proposed for the clinical
      implementation of the new seed. Results for radial dose function, g(L)(r), and
      anisotropy function, F(r, theta), also agree with corresponding MC calculations
      within experimental uncertainties which are smaller for the polymer gel method
      compared to TLD. It is concluded that the proposed polymer gel-magnetic resonance
      imaging methodology could be used at least as a supplement to the established
      techniques for the dosimetric characterization of new low energy and low dose
      rate interstitial brachytherapy seeds.

PMID- 16585849
TI  - Characterization of megavoltage electron beams delivered through a photon multi
      leaf collimator (pMLC).
AB  - A study is presented that characterizes megavoltage electron beams delivered
      through an existing double-focused photon multi-leaf collimator (pMLC) using film
      measurements in a solid water phantom. Machine output stability and linearity
      were evaluated as well as the effect of source-to-surface distance (SSD) and
      field size on the penumbra for electron energies between 6 and 18 MeV over an SSD
      range of 60-100 cm. Penumbra variations as a function of field size, depth of
      measurement and the influence of the jaws were also studied. Field abutment,
      field flatness and target coverage for segmented beams were also addressed. The
      measured field size for electrons transported through the pMLC was the same as
      that for an x-ray beam up to SSDs of 70 cm. At larger SSD, the lower energy
      electron fields deviated from the projected field. Penumbra data indicated that
      60 cm SSD was the most favourable treatment distance. Backprojection of P(20-80)
      penumbra data yielded a virtual source position located at 98.9 cm from the
      surface for 18 MeV electrons. For 6 MeV electrons, the virtual source position
      was at a distance of 82.6 cm. Penumbra values were smaller for small beam slits
      and reached a near-constant value for field widths larger than 5 cm. The
      influence of the jaws had a small effect on the penumbra. The R90 values ranged
      from 1.4 to 4.8 cm between 6 and 21 MeV as measured at 60 cm SSD for a 9 x 9 cm2
      field. Uniformity and penumbra improvement could be demonstrated using weighted
      abutted fields especially useful for small segments. No detectable electron
      leakage through the pMLC was observed. Bremsstrahlung measurements taken at 60 cm
      SSD for a 9 x 9 cm2 field as shaped by the pMLC compared within 1% to
      bremsstrahlung measurements taken at 100 cm SSD for a 10 x 10 cm2 electron
      applicator field at 100 cm SSD.

PMID- 16585850
TI  - Combined anterior-to-posterior and posterior-to-anterior approach to paranasal
      sinus surgery: an update.
AB  - OBJECTIVES: To develop an anatomically and functionally based approach to
      endoscopic intranasal ethmoidectomy; to develop such an approach using the
      salient features of the anterior-to-posterior (AP) and posterior-to-anterior (PA)
      intranasal sinus operations; to assess the safety of this form of ethmoidectomy
      in a patient population. STUDY DESIGN: Retrospective chart review of patients
      undergoing ethmoidectomy by the authors or by residents under their direct
      supervision. SETTING: University teaching hospital. RESULTS: Two thousand three
      hundred and forty-four patients underwent either unilateral or bilateral
      ethmoidectomies between April 1992 and August 2005. A complication rate of 0.34%
      was observed. CONCLUSIONS: Combining an AP approach to conserve sinus anatomy
      with a PA approach to avoid surgery directed toward the skull base provides a
      functional and safe procedure, as demonstrated by the reported results.

PMID- 16585851
TI  - Effects of mitomycin-C on normal dermal fibroblasts.
AB  - OBJECTIVES: To evaluate the effects of mitomycin-C on the growth and autocrine
      growth factor production of human dermal fibroblasts from the face. STUDY DESIGN:
      In vitro study using normal adult dermal fibroblast cell lines in a serum-free
      model. METHODS: Cell cultures were exposed to 4 mg/mL, 0.4 mg/mL, 0.04 mg/mL,
      0.004 mg/mL, and 0.0004 mg/mL concentrations of mitomycin-C solution. Cell counts
      were performed, and the cell-free supernatants were collected at 0, 1, 3, and 5
      days after the initial exposure. Population doubling times were calculated and
      supernatants were quantitatively assayed for basic fibroblast growth factor
      (bFGF) and transforming growth factor (TGF)-beta1. RESULTS: Continuous exposure
      to mitomycin-C caused fibroblast cell death by day 7 at all tested
      concentrations. A 4 minute exposure to mitomycin-C at 4 mg/mL caused rapid
      fibroblast cell death. A 4-minute exposure to mitomycin-C at either 0.4 mg/mL or
      0.04 mg/mL resulted in decreased fibroblast proliferation. A 4 minute exposure to
      mitomycin-C at 0.4 mg/mL resulted in a marked increase in the production of both
      bFGF and TGF-beta1. CONCLUSIONS: A clinically ideal concentration of mitomycin-C
      would slow fibroblast proliferation yet not cause cell death to allow for a wound
      healing response. Mitomycin-C 0.4 mg/mL for 4 minutes satisfies the above
      criteria in vitro.

PMID- 16585852
TI  - Perioperative parathyroid hormone levels in thyroid surgery.
AB  - OBJECTIVE: Perioperative hypocalcemia from temporary parathyroid gland
      dysfunction is common after thyroid surgery. No reliable cutoff values for
      parathyroid hormone (PTH) and the subsequent possibility of developing
      hypocalcemia exist. The purpose of this study is to determine a criterion for
      predicting hypocalcemia based on different PTH levels as cutoff values. STUDY
      DESIGN: Retrospective chart review. METHODS: A centralized database of
      intraoperative PTH levels was analyzed. PTH values approximately 10 minutes after
      excision of the thyroid gland and in the recovery room were obtained; serial
      ionized calcium levels were also analyzed. PTH values were then compared using
      chi-square analysis with significance defined as P < .05. A receiver operator
      characteristic (ROC) curve was also constructed to define sensitivities and
      specificities of different PTH levels as potential cutoff values. RESULTS: Eighty
      patients were identified meeting the study criteria between January 1999 and
      February 2005. Fourteen of the 80 (17.5%) patients became hypocalcemic during the
      hospital stay; none experienced permanent hypocalcemia. Patients who became
      hypocalcemic during their hospitalization were more likely to have a PTH level
      below 15 pg/mL (P < .01). Patients with a PTH level less than 15 pg/mL were more
      likely to develop hypocalcemia (P < .01). Finally, an ROC curve was constructed,
      allowing the surgeon to determine acceptable sensitivities and specificities and
      various PTH cutoff values. CONCLUSION: Low perioperative PTH levels significantly
      correlate with the presence of postoperative hypocalcemia but cannot be used to
      predict it. Using the ROC curve allows different chosen cutoff values to predict
      hypocalcemia with varying sensitivity and specificity.

PMID- 16585853
TI  - Short- and long-term effects of sildenafil on skin flap survival in rats.
AB  - OBJECTIVE: Distal ischemic necrosis of the flap remains an unsolved, challenging
      problem. Phosphodiesterase (PDE) inhibitors, which include the drug sildenafil,
      are a relatively new class of U.S. Food and Drug Administration-approved
      medications whose effect on tissue viability has not been widely explored. The
      vasodilatory effects of these drugs have the potential to enhance blood flow to
      flaps and increase their survivability. The purpose of this study was to examine
      the short- and long-term effects of sildenafil, administered intraperitoneally at
      a dose of 9 mg/kg per day, on the survival of surgical skin flaps in rats.
      METHODS: A McFarlane-type random pattern skin (3 x 10-cm) flap model was used to
      evaluate the effect of sildenafil on necrosis at multiple time points. Rats were
      assigned to sildenafil-treated (9 mg/kg per day intraperitoneally; n = 34),
      vehicle control (n = 35), or sham (no injection; n = 40) groups. In each group,
      caudally based, dorsal, rectangular (3 x 10-cm) flaps were created. Flap necrosis
      was determined using orthogonal polarization spectral imaging and digital
      photography analysis on days 1, 3, 5, and 7 postsurgery. RESULTS: Orthogonal
      polarization spectral imaging results showed a significant decrease in necrosis
      and stasis in rats treated with sildenafil on days 1 and 3. Although reductions
      observed at days 5 and 7 were not as dramatic as days 1 and 3, digital
      photography analysis confirmed a decrease in the area of necrosis at all time
      points evaluated. CONCLUSIONS: These results suggest that PDE 5 inhibitors may
      play a more important role in early postoperative skin flap viability rather than
      at later time points and may be beneficial for skin flap viability as shown in
      the rat model. PDE 5 inhibitors may reduce the extent of necrosis after
      reconstructive surgeries.

PMID- 16585854
TI  - Cochlear protection by local insulin-like growth factor-1 application using
      biodegradable hydrogel.
AB  - OBJECTIVE: The aim of this experimental study was to examine the potential of
      local recombinant human insulin-like growth factor-1 (rhIGF-1) application
      through a biodegradable hydrogel for the treatment of cochleae. METHODS: A
      hydrogel immersed with rhIGF-1 was placed on the round window membrane of Sprague
      Dawley rats while a hydrogel immersed with physiological saline was applied to
      control animals. On day 3 after drug application, the animals were exposed to
      white noise at 120 dB sound pressure level (SPL) for 2 hours. Cochlear function
      was monitored using measurements of auditory brain stem responses (ABRs) at
      frequencies of 8, 16, and 32 kHz. The temporal bones were collected 7 or 30 days
      after noise exposure and the loss of hair cells was quantitatively analyzed.
      RESULTS: Local rhIGF-1 treatment significantly reduced the elevation of ABR
      thresholds on days 7 and 30 after noise exposure. Histologic analysis revealed
      that local rhIGF-1 treatment significantly prohibited the loss of outer hair
      cells. CONCLUSIONS: These findings demonstrate that local IGF-1 application
      through the biodegradable hydrogel has the potential for protection of cochleae
      from noise trauma.

PMID- 16585855
TI  - Parotidectomy for benign parotid disease at a university teaching hospital:
      outcome of 963 operations.
AB  - OBJECTIVE/HYPOTHESIS: The objective of this study was to analyze the
      perioperative and long-term complications after standardized lateral and total
      parotidectomy for benign parotid tumors and chronic parotitis with special regard
      on the training skill of the surgeons at a university teaching center. All
      teaching operations were performed under strict microscopic control and
      supervision of experienced surgeons. STUDY DESIGN: The authors conducted a
      retrospective unicentric study in a tertiary university center. METHODS: Medical
      records of 963 lateral and total parotidectomies treated from 1986 to 2004 were
      analyzed with regard to perioperative and long-term complications. The surgeons'
      expertise to perform a parotidectomy was classified as beginner (0-20
      parotidectomies performed), advanced (21-50), experienced (51-100), or highly
      experienced (>100). RESULTS: Eighty-five percent of the cases were primary
      operations (85%) and 15% revision operations. A lateral parotidectomy was
      necessary in 61% and total parotidectomy in 39%. The mean operation time was 192
      minutes. The incidence of transient facial nerve dysfunction was 25%, and 6% for
      permanent weakness, respectively. Treatment for Frey's syndrome was performed in
      5%. First recurrence for pleomorphic adenoma was observed in 2% and for Warthin's
      tumor in 3%. Significantly more complications were seen after total parotidectomy
      and in revision cases. Beginners and advanced surgeons (operated 41% of the
      cases) needed a longer operation time than experienced and highly experienced
      surgeon (59% of the cases). The surgeon's expertise had no influence on the
      incidence of complications. CONCLUSIONS: Standardized education in lateral and
      total parotidectomy for treatment of benign parotid disease under precise
      microscopic control is safe, demonstrates good results, and has low perioperative
      and long-term morbidity.

PMID- 16585856
TI  - The 30-bp deletion of Epstein-Barr virus latent membrane protein-1 gene has no
      effect in nasopharyngeal carcinoma.
AB  - OBJECTIVE: The specific 30-bp deletion of the Epstein-Barr virus (EBV)-derived
      latent membrane protein-1 gene has been suggested to be associated with the
      pathogenesis of nasopharyngeal carcinoma (NPC) and a more aggressive phenotype of
      some EBV-associated malignancies. METHODS: The authors conducted a retrospective
      cohort study. Between 1995 and 2001, 542 patients who had received complete
      courses of radiotherapy followed by at least 3 years of follow up were enrolled.
      Patients were divided into two groups according to the presence or absence of the
      30-bp deletion in their tumor samples. RESULTS: A total of 446 (82.3%) patients
      were found to feature the 30-bp deletion, whereas 88 (16.2%) did not.
      Interestingly, dual infection was found in eight (1.5%) patients. No statistical
      significance was found in age, gender, NPC-presenting stage, radiosensitivity,
      and pathologic classification between the two groups. The actuarial 5-year
      overall survival rate and the distant metastasis-free rate for the 30-bp deletion
      and nondeletion group were not statistically different (61.3% vs. 65.4% and 68.1%
      vs. 73.1%; P = .132 and .135, respectively). In multivariate analysis, older age,
      nasopharyngeal recurrence, advanced tumor stage, and the development of distant
      metastasis were shown to be poorer prognosticators for overall survival, whereas
      the presence of 30-bp deletion was not. For distant metastasis, only advanced
      tumor stage was shown to be a poor prognosticator, whereas other variables,
      including the presence of 30-bp deletion, had no statistical significance.
      CONCLUSIONS: In this retrospective cohort, we have demonstrated that this
      specific 30-bp sequence deletion might be only the predominant variant rather
      than an NPC phenotype-associated polymorphism. Additionally, dual infection is a
      rare but possible phenomenon in the endemic NPC tumors.

PMID- 16585857
TI  - Helicobacter pylori seropositivity predicts outcomes of acid suppression therapy
      for laryngopharyngeal reflux symptoms.
AB  - OBJECTIVES: Although an inverse relationship has been reported between the rates
      of reflux esophagitis and Helicobacter pylori infection in Japan, infection rates
      among patients complaining of laryngopharyngeal reflux symptoms, such as abnormal
      laryngopharyngeal sensation, chronic coughing, and hoarseness, have not
      previously been investigated. The effects of H. pylori infection on outcomes of
      acid suppression therapy have not been studied. STUDY DESIGN: Retrospective
      cohort study. METHODS: We investigated the relationships between H. pylori
      antibody positivity, laryngopharyngeal reflux symptoms, objective
      laryngopharyngeal findings, and rate of response to acid-suppression therapy in
      42 subjects who were diagnosed with gastroesophageal reflux disease, using upper
      gastrointestinal endoscopy, and were assayed for the serum H. pylori antibody.
      RESULTS: The incidence of H. pylori antibody positivity in the targeted patient
      group was 59.5%. Kaplan-Meier analysis showed that the laryngopharyngeal symptom
      improvement rate, measured using the symptom score, was significantly lower for
      H. pylori antibody-negative cases than for H. pylori antibody-positive cases
      (30.0 vs. 84.6%; P = .002) 60 days after the start of acid-suppression therapy.
      No significant differences in the esophageal symptom-improvement rate were noted
      between the two groups (76.2 vs. 89.5%; P = .576) CONCLUSIONS: By focusing on the
      involvement of H. pylori infection in laryngopharyngeal reflux, we determined the
      relationships between H. pylori antibody positivity and response to acid
      suppression therapy among patients. The laryngopharyngeal, not esophageal,
      symptom relief by acid-suppression therapy was significantly lower among H.
      pylori antibody-negative cases than among antibody-positive cases.

PMID- 16585858
TI  - Long-term results of inferior turbinate hypertrophy with radiofrequency
      treatment: a new standard of care?
AB  - OBJECTIVE: The objective of this study was to report the long-term efficacy of
      radiofrequency volumetric tissue reduction (RFVTR) and to compare this with other
      accepted surgical treatments of inferior turbinate hypertrophy. STUDY DESIGN AND
      SETTING: Prospective, 2-year follow-up of 19 patients originally enrolled in a
      prospective, randomized, single blinded, placebo controlled trial for treatment
      of inferior turbinate hypertrophy with RFVTR. Patients evaluated their severity
      of obstruction, frequency of obstruction, and overall ability to breathe by way
      of a 10 cm visual analogue scale. RESULTS: RFVTR for inferior turbinate
      hypertrophy showed continued benefit at 2 years posttreatment, with no indication
      of increasing symptomatology. The benefit demonstrated in frequency of
      obstruction, severity of obstruction, and overall ability to breathe (P < .05)
      was maintained at 2 years. No complications occurred. Review of the literature
      shows lower short- and long-term complications for RFVTR compared with other
      surgical methods CONCLUSION: RFVTR is effective in treating inferior turbinate
      hypertrophy with sustained benefit at 2 years follow-up while resulting in fewer
      complications than other surgical methods. SIGNIFICANCE: RFVTR is a relatively
      new procedure, and therefore there are few long-term evaluations of its
      effectiveness; this is the first prospective study to document successful
      outcomes at 2 years follow-up.

PMID- 16585859
TI  - Survey anatomy of the paranasal sinuses in the normal mouse.
AB  - OBJECTIVE: To provide researchers with a survey atlas of normal paranasal sinus
      anatomy in the mouse as well as to standardize the reporting of data within the
      murine nose and sinuses. STUDY DESIGN: Histologic and radiographic study in mice.
      METHODS: C57BL/6 mice were killed and their heads sectioned in the axial and
      coronal planes as well as imaged using a small animal micro-computed tomography
      (CT) scanner. Distinctive regions within the nose and paranasal sinuses were
      delineated and labeled A to G for identification. RESULTS: Definable regions
      within the normal murine nose and paranasal sinuses include A) the nasal airway,
      B) the superior nasal vault, C) the osteomeatal complex, D) the anterior ethmoid
      sinuses, E) the posterior ethmoid sinuses, F) the true maxillary sinus, and G)
      the secondary maxillary sinus. Mice also possess discernible sphenoid sinuses. CT
      scans confirmed the histologic plane of section. CONCLUSIONS: A survey atlas of
      normal murine sinonasal anatomy shall provide laboratories seeking to use mice in
      sinus research a reference for beginning their work. As new transgenic and gene
      knockout mice become available, phenotypic changes in sinonasal architecture can
      be more easily discerned using such a reference. Defining specific regions (A-G)
      within the sinuses will standardize the nomenclature used for reporting data.

PMID- 16585861
TI  - Long-term results after endoscopic sinus surgery involving frontal recess
      dissection.
AB  - OBJECTIVE: To assess long-term follow-up on a cohort of patients who underwent
      endoscopic frontal sinus surgery with identification and preservation of the
      natural frontal outflow tract. STUDY DESIGN AND SETTINGS: Retrospective chart
      review, telephone interview, and endoscopic evaluation on a previously studied
      cohort of patients at a university affiliated medical center. RESULTS: Two
      hundred patients who underwent endoscopic frontal sinus surgery were previously
      studied and reported after short-term (mean = 12.2 mo) follow-up. One hundred
      fifty-two (76%) patients were available for long-term (mean 72.3 mo) follow-up
      and assessment of subjective symptoms. Fifty-seven of 152 (37.5%) patients also
      had nasal endoscopy for evaluation of objective findings. The percentage of
      patients responding to telephone interview reporting overall improvement after
      surgery was 92.4%. Endoscopic assessment revealed patency of the frontal sinus in
      67.6% of the patients after initial surgery. Thirteen additional patients had
      patent sinuses after revision procedures, bringing overall patency rate to 71.1%.
      We found statistically significant correlation of asthma and smoking and poor
      subjective and objective outcome. CONCLUSION: Long-term assessment of subjective
      and objective findings in our previously reported cohort of patients who
      underwent frontal sinus surgery indicates that the frontal sinus, similar to any
      other sinus, can be successfully treated surgically by preserving the natural
      frontal sinus outflow tract.

PMID- 16585860
TI  - Evaluation of a navigation system for ENT with surgical efficiency criteria.
AB  - The aim of this study is the evaluation of a navigation system (NaviBase) for ENT
      surgery. For this purpose, a new methodology for the evaluation of surgical and
      ergonomic system properties has been developed. The practicability of the
      evaluation instruments will be examined using the example of the overall
      assessment of the system in comparison with the current surgical standard and
      with other systems using clinical efficiency criteria. The evaluation is based on
      102 ENT surgical applications; of these, 89 were functional endoscopic sinus
      surgeries (FESS). The evaluation of surgical and ergonomic performance factors
      was performed by seven ENT surgeons. To evaluate surgical system properties, the
      Level of Quality (LOQ) in 89 cases of the FESS was determined. It compares the
      existing information of the surgeon with that of the navigation system on a scale
      of 0 to 100 and with a mean value of 50 and places it in a relationship to the
      clinical impact. The intraoperative change of the planned surgical strategy
      (Change of Surgical Strategy) was documented. The ergonomic factors of the system
      with the categories of Overall Confidence (Trust), awareness of the situation
      (Situation Awareness), influence on the operating team, requirements for specific
      skills (Skill Set Requirement), and cognitive load (Workload Shift) were recorded
      for all surgical procedures as Level of Reliance (LOR). In the evaluation of the
      surgical system properties, an average evaluation of the quality of the
      information, as an LOQ of 63.59, resulted. Every second application of the
      navigation system (47.9%), on average, led to a change in the surgical strategy.
      An extension/enhancement of the indication of the endonasal approach through the
      use of the navigation system was shown in 7 of 102 (6.8%) cases. The completion
      of the resection in the FESS was rated by 74% of group I and 11% of group II as
      better in comparison with the standard approach. Total confidence shows a
      positive evaluation of 3.35 in the LOR. To supplement the evaluation of the
      navigation system, the technical parameters were included. The maximum deviation,
      Amax, of the displayed position of the reference value amounted to 1.93 mm. The
      average deviation was at 1.29 mm with an SD above all values, sd, of 0.29. The
      subsequent economic evaluation resulted in an effective average extra expenditure
      of time of 1.35 minutes per case. The overall evaluation of the system imparts
      application-relevant information beyond the technical details and permits
      comparability between different assistance systems.

PMID- 16585862
TI  - Impact of gland morphology and concomitant thyroid nodules on preoperative
      localization of parathyroid adenomas.
AB  - OBJECTIVES: Primary hyperparathyroidism (pHPT) is a common endocrine disease. The
      aim of this study was to assess the effect of the presence of thyroid nodules,
      adenoma weight, and ectopic localization on the sensitivity of different imaging
      studies in patients with hyperparathyroidism. STUDY DESIGN: A series of 125
      patients with pHPT who underwent low-frequency ultrasonography, high-frequency
      ultrasonography, Thallium-Technetium scintigraphy, sestamibi scintigraphy, and
      combined technique was reviewed retrospectively. Patients were divided in two
      groups depending on the presence or absence of thyroid nodules. RESULTS: The
      overall sensitivity of low-frequency ultrasonography, high-frequency
      ultrasonography, Thallium-Technetium scintigraphy, sestamibi scintigraphy, and
      combined technique was 69%, 89%, 71%, 86%, and 98%, respectively. The sensitivity
      of these imaging studies was 94%, 100%, 94%, 96%, and 100%, respectively, in our
      patients with no thyroid nodules but decreased to 54%, 84%, 54%, 81%, and 79%,
      respectively, in the presence of thyroid nodules. The parathyroid adenoma weight
      in true-positive imaging studies was significantly higher than those in false
      positive and false-negative imaging studies. The numbers of ectopic parathyroid
      adenomas were found to be higher in the group of parathyroid adenomas undetected
      with ultrasonography when compared with ultrasonographically detected adenomas.
      CONCLUSION: In patients with parathyroid adenoma, the sensitivity of imaging
      studies correlates with the presence of thyroid nodules, adenoma weight, and
      ectopic localization.

PMID- 16585863
TI  - Scanning electron microscopy of ciliae and saccharine test for ciliary function
      in septal deviations.
AB  - OBJECTIVE: To investigate the difference in mucociliary clearance and surface
      mucosal structure of the nasal septum and lateral nasal wall in patients with and
      without septal deviation. METHOD: The saccharine-dye test was used to measure the
      mucociliary clearance time in both nasal cavities of 20 patients with nasal
      septal deviation (study group) and was compared with that of 30 patients without
      septal deviation (control group). Bilateral septal and lateral nasal wall mucosal
      biopsies were taken from the study group during septoplasty, and unilateral
      biopsies were taken from 10 of the control group. These biopsies were studied
      under the scanning electron microscope. RESULTS: In the study group, mucociliary
      clearance on the side opposite the septal deviation was significantly slower than
      on the other side. Mucociliary clearance on both sides of the deviated septum of
      the study group was significantly slower than clearance in the control group.
      There was no statistically significant difference in the distribution of mucosal
      cilia of the cavities on either side of the deviated septum in the study group,
      nor between the distribution in the study group and controls. CONCLUSION:
      Patients with septal deviation display no change in mucosal surface anatomy but
      have decreased mucociliary activity on both sides of the deviation, the least
      activity being on the side opposite the deviation.

PMID- 16585864
TI  - Lidocaine block of the recurrent laryngeal nerve in adductor spasmodic dysphonia:
      a multidimensional assessment.
AB  - OBJECTIVES/HYPOTHESIS: Lidocaine block of the recurrent laryngeal nerve (RLN) has
      been reported as a procedure for surgical selection of patients with adductor
      spasmodic dysphonia (ADSD). However, its effects on phonation have not been
      rigorously assessed in a prospective fashion using strict entry criteria and
      multiple measures of phonatory function. This investigation assessed the
      phonatory effects of RLN lidocaine block in ADSD to explore its potential as a
      diagnostic tool. STUDY DESIGN: Single group, pre/postexperimental trial. METHODS:
      Twenty-one consecutive patients with suspected ADSD underwent unilateral RLN
      block, causing temporary ipsilateral vocal fold paralysis. Voices were recorded
      before and during the block. Patients completed self-ratings of overall level of
      dysphonia severity, vocal effort, and laryngeal tightness. Blinded listeners
      completed auditory-perceptual ratings, and the frequency of phonatory breaks was
      acoustically analyzed. RESULTS: During the block, patients reported significant
      reductions on overall severity (P = .045), vocal effort (P < .001), and laryngeal
      tightness (P = .002). Listeners rated the voices during the block as
      significantly more breathy (P < .001), less strained (P < .001), and less severe
      (P = .059). Acoustic analysis confirmed significantly fewer phonatory breaks
      during the block (P < .001). Patient-based ratings of improvement were more
      consistent than listener ratings, and reduction in overall severity correlated
      with perceived breathiness. CONCLUSIONS: Although individuals varied in their
      outcomes, group results suggest that response to RLN lidocaine block warrants
      further study as a possible diagnostic tool in ADSD.

PMID- 16585865
TI  - Growth suppression of human laryngeal squamous cell carcinoma by adenovirus
      mediated tissue factor pathway inhibitor gene 2.
AB  - OBJECTIVE: The purpose of this study was to explore the inhibiting role of
      adenoviral-mediated (Ad)-tissue factor pathway inhibitor (TFPI)-2 gene in the
      growth of laryngeal squamous cell carcinoma (LSCC). STUDY DESIGN: The nude mice
      bearing LSCC were prepared by intracutaneous injection of Hep-2 cell. Gene
      therapy was performed by injecting adenoviruses carrying TFPI-2 gene around
      tumors in the animal model. METHODS: Eighteen nude mice bearing Hep-2 cell tumor
      were randomly separated into the treated group and control group. The former were
      injected with recombinant adenovirus Ad-TFPI-2 around the tumor, and the later
      were injected with equivalent Ad-LacZ. After treatment, differences of tumor
      weight, volume, and ultrastructure of tumor cells between these two groups were
      observed by measuring and using transmission electron microscope. Apoptosis in
      Hep-2 xenotransplants was detected using the terminal deoxy-transferase-mediated
      dUTP nick end labeling. In addition, the expressions of TFPI-2 protein and
      proliferating cell nuclear antigen (PCNA) in tumor tissues were detected using
      Western blot and immunohistochemistry, respectively. RESULTS: The average weight
      and volume of tumor in the treated group were significantly lower than that in
      the control group (P < .01). The PCNA index was obviously lower in the tumors
      treated group than that in the control group (P < .01). In addition, cell
      apoptosis was observed in xenotransplants of the treated group but not in the
      control group. CONCLUSION: Peritumor injection of Ad-TFPI-2 can inhibit growth of
      LSCC in nude mice model, and TFPI-2 might be a desirable gene for gene therapy in
      LSCC.

PMID- 16585866
TI  - Rofecoxib versus hydrocodone/acetaminophen for postoperative analgesia in
      functional endoscopic sinus surgery.
AB  - OBJECTIVES/HYPOTHESIS: Functional endoscopic sinus surgery (FESS) is less
      invasive and more tissue sparing than extirpative techniques, with an assumed
      benefit of diminished postoperative pain. Oral opioids are commonly prescribed
      after sinus surgery but are associated with adverse effects, including
      gastrointestinal and neurologic symptoms. Nonopioid analgesics have been
      suggested to offer similar pain control efficacy with fewer adverse effects.
      STUDY DESIGN: To investigate postoperative analgesia in FESS, a prospective
      randomized, double-blinded comparison of hydrocodone/acetaminophen 7.5/750 mg (an
      opioidderivative) with rofecoxib 50 mg (a cyclooxygenase-2 inhibitor) was
      performed. METHODS: Forty subjects were enrolled, of which 28 successfully
      completed the study. Subjects recorded peak pain levels and requirement for
      rescue analgesia on the day of surgery and for 4 days thereafter. On
      postoperative day 5, subjects completed an exit survey in which adverse effects
      and overall satisfaction with pain control were recorded. RESULTS: In this study,
      there were no statistical differences in peak pain levels between the groups at
      any point in the postoperative period, regardless of extent of surgery. Adverse
      effect profiles were also similar for the two groups. CONCLUSIONS: The use of
      nonopioid analgesics after FESS may provide similar pain control to oral opioids.

PMID- 16585867
TI  - Long-term results of a multimodal intensification regimen for previously
      untreated advanced resectable squamous cell cancer of the oral cavity,
      oropharynx, or hypopharynx.
AB  - BACKGROUND: Long-term disease control of an intensified treatment regimen for
      previously untreated stage III and IV resectable oral cavity, oropharyngeal, or
      hypopharyngeal squamous cell carcinoma was analyzed. METHODS: Forty-three
      patients with previously untreated, advanced stage, resectable squamous
      carcinomas of the oral cavity, oropharynx, or hypopharynx were enrolled in a
      prospective phase II institutional clinical trial at a tertiary care National
      Cancer Institute-designated comprehensive cancer center. It includes preoperative
      accelerated hyperfractionated radiotherapy with concurrent cisplatin followed
      immediately by surgery and intraoperative radiotherapy, and completed with early
      postoperative weekly paclitaxel, two additional cisplatin cycles, and concurrent
      once-daily radiotherapy beginning on day 28 after surgery. RESULTS: Forty-three
      patients enrolled in the study. Protocol compliance was 53%. The range of time at
      risk was 10.4 to 56.23 months (median, 45 months). The locoregional (93%) and
      systemic (91%) disease control rates were excellent. Overall long-term survival
      was 79%. CONCLUSIONS: An intensive treatment regimen that improves compliance and
      long-term disease control is clearly feasible for this patient population.

PMID- 16585868
TI  - Phase II study of weekly docetaxel and cisplatin in patients with advanced
      recurrent and metastatic head and neck cancer.
AB  - OBJECTIVE: Response rates of presently used palliative chemotherapy for end-stage
      recurrent head and neck cancer are poor, but the regimes cause important
      toxicity. METHODS: A prospective phase II study was conducted to evaluate the
      activity and toxicity of a weekly combination of cisplatin and docetaxel in
      patients with recurrent head and neck cancer. From July 2003 to November 2004, 21
      patients with metastatic neck disease were enrolled. Treatment consistent of 25
      mg/m cisplatin and 35 mg/m docetaxel once a week for 3 weeks followed by 1 week
      without treatment for each cycle. The primary end point was median survival.
      Secondary end points were response rate (RECIST), time to progression, toxicity
      (NCI-CTC), and quality-of-life (EORTC QLQ-C30, QLQ-H&N35). RESULTS: Eight
      patients (42%) showed a partial response. Eight patients (42%) had stable
      disease. Progressive disease was seen in three patients (16%). The median follow
      up time was 7.2 months (95% confidence interval [CI], 5.9-9.3 months). The median
      time to progression was 3.5 months (95% CI, 2.0-5.0 months). The median overall
      survival was 10.7 months (95% CI, 6.4-15.0 months). Grade 3 toxicities occurred
      in two patients (10%). A grade 4 adverse event was not recorded. Most global
      quality-of-life scores but not head and neck-specific scores are deteriorated
      after last chemotherapy. CONCLUSION: Weekly docetaxel and cisplatin is active in
      recurrent head and neck cancer and shows an excellent toxicity profile. Its
      influence on the stabilization of quality of life is less significant.

PMID- 16585869
TI  - Petrous bone cholesteatoma: management and outcomes.
AB  - OBJECTIVE: Cholesteatoma of the petrous bone is a rare pathology that grows
      slowly and is often asymptomatic. High clinical suspect is recommended for its
      diagnosis. With the advancement of imaging, clinical diagnosis is confirmed and
      follow up is assured. The present study is presented to state our experience in
      management of petrous bone cholesteatoma (PBC) and an overview of the outcome
      results. METHODS: This study was a retrospective case review conducted at a
      private quaternary referral center. From January 1984 to October 2004, 93 of
      2,739 patients with chronic otitis media with cholesteatoma were treated
      surgically for PBC with varying location types. RESULTS: The mean age in this
      study was 46 years. Ninety-four percent of patients presented with hearing loss.
      Facial paralysis constituted 55% of the presented manifestations and grade VI
      palsy was the most common. A massive type of PBC was found to affect 45% of
      patients and it was mainly the acquired pathology. The surgical approaches varied
      according to the class type of PBC. Postoperative complications were minimal, and
      follow up was carried out after 1 year from the surgery date. CONCLUSION: Petrous
      bone cholesteatoma presents difficulties in its diagnosis and treatment. Adequate
      history-taking, high clinical suspicious, with the advancement of imaging
      techniques made its diagnosis more feasible. Improvement of the lateral skull
      base approaches rendered possible safe, adequate, and complete removal of the
      pathology.

PMID- 16585870
TI  - Protective effects of glucocorticoids on ischemia-reperfusion injury of outer
      hair cells.
AB  - OBJECTIVE: This animal study aimed to investigate effects of glucocorticoids on
      the functional recovery of outer hair cells (OHCs) after transient ischemia.
      METHODS: Distortion-product otoacoustic emission (DPOAE) was examined before,
      during, and after transient cochlear ischemia of 30 minutes using albino guinea
      pigs. RESULTS: DPOAE decreased to noise level during ischemia. On recirculation,
      DPOAE initially recovered with time until 20 minutes after the onset of
      reperfusion, but thereafter, the DPOAE level gradually decreased toward the noise
      level in the control animals. Prednisolone and methylprednisolone significantly
      improved the DPOAE level 60 minutes after the onset of reperfusion. CONCLUSIONS:
      The present findings suggest that glucocorticoids possess protective effects
      against ischemia-reperfusion injury of OHCs.

PMID- 16585871
TI  - Endoscopic laryngotracheal cleft repair without tracheotomy or intubation.
AB  - OBJECTIVES: The objectives of this study are to present the technique and results
      of endoscopic repair of laryngotracheoesophageal clefts (LTEC) extending caudally
      to the cricoid plate into the cervical trachea and to revisit the classification
      of LTEC. METHODS: The authors conducted a retrospective case analysis consisting
      of four infants with complete laryngeal clefts (extending through the cricoid
      plate in three cases and down into the cervical trachea in one case) treated
      endoscopically by CO2 laser incision of the mucosa and two-layer endoscopic
      closure of the cleft without postoperative intubation or tracheotomy. RESULTS:
      All four infants resumed spontaneous respiration without support after a mean
      postoperative period of 3 days with continuous positive airway pressure (CPAP).
      They accepted oral feeding within 5 postoperative days (range, 3-11 days). No
      breakdown of endoscopic repair was encountered. After a mean follow up of 48
      months (range, 3 mos to 7 y), all children have a good voice, have no sign of
      residual aspiration, but experience a slight exertional dyspnea. CONCLUSION: This
      limited experience on the endoscopic repair of extrathoracic LTEC shows that a
      minimally invasive approach sparing the need for postoperative intubation or
      tracheotomy is feasible and safe if modern technology (ultrapulse CO2 laser,
      endoscopic suturing, and postoperative use of CPAP in the intensive care unit) is
      available.

PMID- 16585872
TI  - Long-term follow-up results of selective laryngeal adductor denervation
      reinnervation surgery for adductor spasmodic dysphonia.
AB  - Selective laryngeal adductor denervation-reinnervation surgery for the treatment
      of adductor spasmodic dysphonia was reported in 1999 in 21 patients with
      encouraging results. Here, we report long-term results of this procedure.
      Surgical outcome was evaluated using patient surveys and perceptual voice
      assessment. Measured outcomes included Voice Handicap Index (VHI)-10 scores,
      patient questionnaire, and perceptual evaluation for voice breaks and
      breathiness. Patient survey was obtained from 83 patients, and perceptual voice
      evaluation was performed in voice samples from 46 patients. Average follow-up
      interval was 49 months. Mean VHI-10 scores improved from a mean of 35.6 to 12.7.
      Eighty-three percent showed significantly improved VHI-10 scores, representing
      improved physical, social, and emotional well-being. There was a high degree of
      patient satisfaction, with 91% agreeing that their voice is more fluent after the
      surgery. Perceptual evaluation of postoperative voice samples revealed voice
      breaks in 26% (15% mild, 4% moderate, 7% severe) and breathiness in 30% (11%
      mild, 13% moderate, 6% severe). A majority of patients had stable, long-lasting
      resolution of spasmodic voice breaks.

PMID- 16585873
TI  - Involuntary glottal closure during inspiration in muscle tension dysphonia.
AB  - OBJECTIVE/HYPOTHESIS: The purpose of this study was to examine respiratory
      function in a group of patients with muscle tension dysphonia (MTD) DESIGN: Cross
      sectional analytical study. METHODS: Participants included 15 people with a
      diagnosis of MTD referred to speech pathology for management of their voice
      disorder, fiberoptic evidence of glottal or supraglottic constriction during
      phonation with or without posterior chink, or bowing combined and deviation in
      perceptual voice quality. A second group of 15 participants with no history of
      voice disorder served as healthy controls. Baseline pulmonary function test
      measures included forced expiratory volume in the first second (FEV1), FVC, FEF25
      to 75, FIF50, FEV1/FVC, ratio and FEF50/FIF50 ratio. Hypertonic saline challenge
      test measures included FEV1 and FIF50 after provocation, dose response slope, and
      provocation dose. RESULTS: Compared with healthy controls, participants with MTD
      demonstrated a higher prevalence of glottal constriction during inspiration after
      provocation with nebulized hypertonic saline as demonstrated by a reduction in
      FIF50 after the hypertonic saline challenge. There was no significant difference
      between the MTD and healthy control groups in baseline pulmonary function
      testing. Participants with MTD demonstrated a higher prevalence than healthy
      controls of abnormal glottic closure during inspiration similar to paradoxical
      vocal fold movement (PVFM). This suggests that they either had previously
      undiagnosed coexisting PVFM or that the condition of MTD could be expanded to
      include descriptions of aberrant glottic function during respiration. This study
      enhances the understanding of PVFM and MTD by combining research advances made in
      the fields of otolaryngology and respiratory medicine.

PMID- 16585874
TI  - Laryngoscopic detection of pharyngeal carcinoma in situ with narrowband imaging.
AB  - OBJECTIVES: Narrowband imaging (NBI) is a novel optical technique that enhances
      the diagnostic capability of endoscopes in characterizing tissues by using narrow
      bandwidth filters in a video endoscope system. The purposes of this study were to
      verify the effectiveness of the NBI system in conducting endoscopic screening at
      the oropharynx and the hypopharynx. METHODS: This study was conducted between
      July 2005 and August 2005. During this period, 217 consecutive patients with
      esophageal cancer underwent endoscopic screening of the oropharynx and the
      hypopharynx with the NBI system at the Department of Otolaryngology, Keiyukai
      Sapporo Hospital. RESULTS: Among 217 patients, 6 superficial lesions, at the
      oropharynx (n = 1) and at the hypopharynx (n = 5), were discovered with the NBI
      system. On conventional electroendoscopic view, four of six lesions could be
      hardly recognized because of its small diameter measuring 5 mm or less. The NBI
      view was more beneficial in recognizing the superficial lesions than conventional
      electroendoscopic view. Endoscopic mucosal resection was performed for all six
      patients under general anesthesia in the operation room. The histologic
      examination exhibited a histologically proven squamous cell carcinoma (SCC) in
      situ. In our series, the NBI system might improve the sensitivity by about
      twofold over the conventional method. CONCLUSION: NBI may play an important role
      in the diagnosis of SCCs of the oropharynx and hypopharynx.

PMID- 16585875
TI  - Laser-assisted voice adjustment (LAVA) in transsexuals.
AB  - OBJECTIVE: The objective of this study was to evaluate results of laser-assisted
      voice adjustment (LAVA) surgery in male-to-female (MTF) transsexual patients with
      androphonia. METHODS: The authors conducted a prospective case-control study of
      MTFs who underwent CO2 laser vocal fold vaporization between 1997 and 2003.
      Thirty-one patients were self-referred for voice feminization. Pre- and
      postoperative evaluations were completed. Patients' voices were recorded to
      obtain Fo before and after surgery. Voice Handicap Index (VHI) questionnaires
      were completed by post-LAVA patients. A panel of blinded listeners identified
      patients as male or female based on samples of connected speech recorded over the
      telephone. RESULTS: Mean follow-up (23 weeks) revealed pitch increases averaging
      26 Hz. Self-evaluations revealed increases in voice femininity, congruity with
      self-image, and satisfaction. However, the evaluations also showed decreased
      vocal quality, loudness, and vocal range. Mean VHI was consistent with VHI scores
      associated with Reinke's edema. Six of 10 patients were consistently perceived as
      female. CONCLUSION: LAVA provides a conservative treatment for androphonia.
      Postoperative voice therapy may optimize outcomes.

PMID- 16585876
TI  - Sinonasal adenoid cystic carcinoma seeding to the tracheostomy site.
AB  - Neoplastic seeding of head and neck carcinomas is a well-documented but
      relatively rare occurrence. We report a rare case of seeding of a sinonasal
      adenoid cystic carcinoma to a tracheostomy site.

PMID- 16585877
TI  - Subglottic stenosis in Erdheim-Chester disease: a previously unrecognized site of
      involvement.
AB  - We describe a case of laryngeal stenosis secondary to an etiology not previously
      described. A patient with Erdheim-Chester disease presented with airway
      obstruction and was found to have subglottic stenosis. Biopsy results confirmed
      Erdheim-Chester nodules as the cause of the obstruction. This case illustrates
      the need for biopsy to rule out malignancy and less common etiologies of
      subglottic stenosis.

PMID- 16585878
TI  - Pseudoaneurysm of the lingual artery after temperature-controlled radiofrequency
      tongue base reduction: a severe complication.
AB  - Temperature-controlled radiofrequency reduction (TCRF) of the tongue base has
      been developed as an alternative option for the treatment of patients with
      obstructive sleep apnea syndrome. The technique is propagated as an easy and safe
      surgical method. The case of a 34-year-old male patient with obstructive sleep
      apnea syndrome who underwent TCRF is reported. Fourteen days after surgery was
      performed, heavy bleeding at the base of the tongue occurred. Computed tomography
      and digital subtraction angiography imaging revealed a pseudoaneurysm of the
      lingual artery, which was treated endovascularly by detachable and free platinum
      coils during the same session. The article reports the first case of
      pseudoaneurysm under TCRF of the tongue base and discusses the diagnostic and
      therapeutic procedure to handle and avoid life-threatening complications under
      this method of treatment.

PMID- 16585879
TI  - Lingual tonsillectomy in a child with obstructive sleep apnea: a novel technique.
AB  - We report on a case of lingual tonsillar hyperplasia contributing to refractory
      obstructive sleep apnea in a 5-year-old patient. We describe a novel technique
      utilizing suspension laryngoscopy and a laryngeal angled shaver to remove
      obstructive lingual tonsillar tissue. We review the available techniques for
      lingual tonsillectomy and propose theoretical advantages to the novel approach.

PMID- 16585880
TI  - In-office determination of cricoarytenoid joint mobility.

PMID- 16585881
TI  - Seldinger technique for insertion of a nasogastric tube.

PMID- 16585882
TI  - [Evolution of the concept of transient ischaemic attacks].

PMID- 16585883
TI  - [The neurology of pregnancy].

PMID- 16585884
TI  - [Fatigue and episodic exhaustion as a feature of multiple sclerosis].

PMID- 16585885
TI  - [Multiple sclerosis and pregnancy].
AB  - The influence of pregnancy in multiple sclerosis (MS) has been a matter of
      controversy for a long time. Women with MS were often discouraged to envisage
      pregnancy. The Pregnancy in Multiple Sclerosis (PRIMS) study was the first large
      scale prospective study aimed at assessing the possible influence of pregnancy
      and delivery on the clinical course of MS. Two hundred and fifty-four women with
      a diagnosis of MS were included during pregnancy and followed-up till the end of
      the second year post partum. The results were a reduction in the relapse rate
      during pregnancy, in comparison to the year before pregnancy, especially marked
      in the third trimester, and a significant increase in the relapse rate in the
      first trimester post partum. From the second trimester post partum on however,
      the relapse rate did not significantly differ from the pre-pregnancy rate. About
      one third of the women experienced a post partum relapse. Pregnancy did not
      influence disability progression. The clinical factors likely to predict a
      relapse in the three months after delivery were analyzed by logistic regression
      analysis. Women with a greater disease activity in the year before pregnancy and
      during pregnancy had a higher risk of relapse in the post partum three months.
      Neither breast-feeding, nor epidural analgesia correlated with presence of a post
      partum relapse. When comparing the predicted and observed status however, only 72
      percent of the women were correctly classified by the multivariate model. It
      seems unwise therefore to use this kind of model to select women that would
      benefit from a putative preventive therapy. The PRIMS study had other major
      consequences: it fostered the development of specific therapeutic strategies to
      prevent post partum relapses (IV immunoglobulins, IV methylprednisolone), and
      suggested a potential role of sexual hormones in the natural history of MS during
      pregnancy and the post partum, therefore identifying them as a preferential
      target for prevention. The preventive effect of progesterone combined with
      estradiol on post partum relapses will be tested in a large-scale randomized and
      placebo-controlled European trial, the POPART'MUS study.

PMID- 16585886
TI  - [Pathophysiology and treatment of fatigue in multiple sclerosis].
AB  - Patients suffering from multiple sclerosis (MS) frequently complain of fatigue
      (53 to 92 percent depending on studies). Fatigue can be one of the most disabling
      symptoms of MS and presents as physical or mental fatigue in daily living
      activities. Besides this permanent feeling of exhaustion, MS patients can suffer
      from an abnormal tiredness and lack of energy after a given motor or mental task,
      which defines fatigability. A number of studies explored the origins of fatigue
      and fatigability by means of subjective and objective tools. The implication of
      central nervous system dysfunctions has been established in several studies;
      however the contribution of peripheral nervous system factors and systemic
      abnormalities associated with inflammatory and immunological parameters was also
      suggested. The aim of this review is to present the different types of fatigue
      and fatigability occurring in MS patients, their origins, the investigation tools
      which allow the quantification of fatigue and fatigability and characterization
      of their mechanisms. The currently available therapeutic strategies that have
      been proposed to relieve this disabling symptom are presented.

PMID- 16585887
TI  - [Management of malignant gliomas diagnosed during pregnancy].
AB  - INTRODUCTION: Glioma is seldom diagnosed during pregnancy. In this situation
      management presents difficult problems for both neuro-oncologists and
      obstetricians. We report four cases and discuss the management of this unusual
      situation. CASE REPORT: The first patient was admitted to hospital at 29 weeks'
      gestation because of a generalized seizure and a right hemiparesis. MRI showed a
      left fronto-insular lesion. A stereotactic biopsy was obtained and revealed an
      anaplastic oligodendroglioma. With corticosteroids the patient remained stable
      until cesarean delivery at 36 weeks. In post-partum additional treatment with
      chemotherapy was started. The second patient was hospitalized at 26 weeks'
      gestation because of cranial hypertension, right hemiparesis and aphasia. MRI
      showed an important left fronto-parietal lesion. Partial resection was performed
      at 28 weeks. Histology revealed a glioblastoma multiforme. With corticosteroids
      the patient remained stable until cesarean delivery at 33 weeks. In post-partum
      additional treatment with radiotherapy and chemotherapy was started. The third
      patient was admitted to the hospital at 12 weeks' gestation because of cranial
      hypertension. MRI showed a left frontal lesion. A subtotal resection was done at
      13 weeks. Histology revealed a glioblastoma multiforme. Two weeks after surgery
      the patient's neurological condition worsened and in agreement with the patient a
      therapeutic abortion was decided. Afterwards additional treatment with
      radiotherapy and chemotherapy was started. The last patient received combined
      treatment with radiotherapy and chemotherapy for local recurrence of a
      mesencephalic high-grade glioma. A posteriori it was discovered that the patient
      was at 4 months' gestation during this treatment. Cesarean delivery was done at
      36 weeks. The child was normal at birth and is still in good health 5 years
      later. CONCLUSION: The management of gliomas diagnosed during pregnancy should
      not be different from the standard management of gliomas in young non-pregnant
      adults. Pregnant women because of their young age can have a long survival. Their
      pregnancy should not prevent them from receiving the best treatment for their
      glioma. Treatment will depend upon clinico-radiological presentation, histology,
      gestational age and the patient's desires. Generally speaking, surgical resection
      of high-grade gliomas should not be delayed during pregnancy. Progress in
      anesthesia and neurosurgery have greatly reduced the risks for the foetus. After
      delivery, if the delay between surgery and delivery is too long it is possible to
      begin cerebral radiotherapy during pregnancy. After the first trimester of
      gestation this treatment can be given without any important risks for the child.

PMID- 16585888
TI  - [Myasthenia gravis and pregnancy: clinical course and management of delivery and
      the postpartum phase].
AB  - OBJECTIVES: To study influences of pregnancy on the time-course of myasthenia
      gravis (MG) and of MG on pregnancy, delivery, postpartum and newborn. METHODS: We
      retrospectively collected data from 100 women affected with MG, hospitalized
      between 1994 and 2003 in departments of Neurology of Lille University Hospital.
      RESULTS: Eighteen patients had a total of 36 pregnancies, occurring 7.2 years on
      average after MG onset. MG exacerbation occurred in 7 patients (26 percent)
      during pregnancy and in 4 (14.8 percent) during postpartum. One patient died of
      acute respiratory failure during postpartum. Delay between the onset of MG and
      pregnancy was the only variable significantly associated with MG exacerbation:
      5.8 years when exacerbation and 9.5 years when no exacerbation (p=0.03). Seven
      miscarriages, two therapeutic abortions and no death at birth were reported.
      Levels of anti-acetylcholine receptor antibodies were abnormal in 3 of 27
      newborns (11 percent), but only one (3.7 percent) developed seronegative
      transient neonatal myasthenia gravis. DISCUSSION: During pregnancy, the clinical
      course of MG is variable but exacerbations were associated with a shorter delay
      between MG diagnosis and pregnancy. The risk of transient neonatal myasthenia
      gravis is relatively small but exists even when the parturient has stable MG
      without elevated levels of anti-acetylcholine receptor antibodies. CONCLUSION:
      Our study confirms pregnancy is more difficult to manage at the beginning of MG.
      Given the unpredictable course of MG during pregnancy, we recommend women
      affected with MG to begin a pregnancy when the disease is stable.

PMID- 16585889
TI  - [Misdiagnosis of mitochondrial myopathies: a study of 12 thymectomized patients].
AB  - INTRODUCTION: Myasthenia gravis and mitochondrial myopathies have common symptoms
      (fatigability, ophthalmoplegia) that could lead to diagnosis confusion. METHODS:
      We systematically reviewed medical history and ancillary investigations regarding
      12 patients (7F/5M, mean age 47+/-14 years) having a mitochondrial myopathy but
      who were previously misdiagnosed as autoimmune myasthenia gravis and in whom a
      thymectomy was performed. RESULTS: Ocular palsy, ptosis and bulbar palsy were
      present in all patients. Limb fatigability was present in 9 cases. Symptoms were
      fluctuant but without remission. The misdiagnosis of myasthenia was based on the
      following arguments: 1) decremental EMG response (2 cases); 2) positive
      injectable anticholinesterase drugs test (3 cases); 3) partial response to oral
      anticholinesterase medications (2 cases); 4) AChR antibodies titer of 0.6 nM
      considered as positive (1 case). A multisystemic involvement was present in 5
      patients: peripheral neuropathy (2 cases), deafness (2 cases), cardiopathy (3
      cases), cerebellar involvement (2 cases) and myoclonia (1 case). The diagnosis of
      mitochondrial myopathy (at a mean age of 38+/-12 years) has been certified on the
      results of muscle biopsy showing mitochondrial proliferation (12 cases) and
      deleted mitochondrial DNA (8 cases). CONCLUSIONS: In a patient presenting with
      oculomotor symptoms and muscle fatigability, progressive course and multisystemic
      involvement are major arguments for a mitochondrial myopathy. In the absence of
      relevant criteria arguing for Myasthenia Gravis (significant variability of
      muscle weakness, positive titer of anti-AChR or anti-MuSK antibodies, decremental
      EMG response), a muscle biopsy is required before indication of thymectomy to
      exclude a mitochondrial disease.

PMID- 16585890
TI  - [Patterns of prescription and usage of triptans in Alsace (France): misuse is
      frequent and avoidable].
AB  - AIMS: To analyze use of triptans in the Alsace region of France: patients,
      disorders motivating, doses, analgesics and migraine prophylactics associated
      treatments, contra-indications. To study major consumers (more than 144 intakes
      per year) and to determine among them the proportion who suffering from chronic
      headache. METHOD: Data concerning all prescriptions of triptans and analgesics as
      well as migraine prophylaxis prescriptions were obtained from the computer
      databases of five of the French National Health's local health agencies in
      Alsace, recorded between April 1, 2003 and March 31, 2004. Data about motivating
      disorders and the clinical context were obtained using a questionnaire sent to
      prescribers. Data about patients with more than 144 intakes per year were
      provided by medical advisors of French Health insurance. RESULTS: We founded
      20686 users: 92.1 percent used between 0 and 6 intakes per month. 11.5 percent of
      disorders motivating the prescription that were mentioned by prescribers were for
      off-label use: tension-type headache 2.7 percent, mixed headache, 8.8 percent.
      Prescribers declared at least one contra-indication for triptan use for 7.8
      percent of patients. Over all, prescriptions were off-label for 16.1 percent of
      patients. Patients who used more than 144 intakes per year accounted for 1.9
      percent of the total number and self-medication accounted for 19.2 percent of all
      triptan intakes. Half of the patients were suffering from daily chronic headache
      (chronic migraine in 66 percent). 15.6 percent of these patients presented at
      least one contraindication (high blood pressure or ischemic disease). All in all
      we estimate that use of triptan is a misuse for 25 percent to 30 percent of the
      intakes. Quantities of other analgesics used increased simultaneously with
      triptan use: on average 65, 119 and 244 Defined Daily Doses (DDD)/person/year for
      patients who used between 1 and 72, 73 and 144 and more than 144 intakes
      respectively. On average 35.4 percent (in DDD) of analgesics used were opiates
      (dextropropoxyphene, codeine, tramadol). This proportion increased simultaneously
      with triptan use: 58.9 percent for major users. Prophylactic treatment for
      migraine was used by 27.9 percent of the patients: lack of prophylaxis was a
      prescriber's choice in 90 percent of the cases. CONCLUSIONS: The high rate of
      triptan misuse emphasizes the importance of improving prescription of these
      drugs.

PMID- 16585891
TI  - [Severe Guillain-Barre syndrome and pregnancy: two cases with rapid improvement
      post-partum].
AB  - INTRODUCTION: Guillain-Barre syndrome can occur at any time of pregnancy with the
      same incidence as in the general population. Observations. We report two cases of
      patients who developed a progressive ascending paralysis during the second
      trimester of pregnancy. The worsening of the respiratory insufficiency for one of
      them required a transfer to an intensive care unit for artificial ventilation
      lasting 102 days. In the two cases, cerebrospinal fluid examination revealed
      albumin-cytological dissociation and repeated electrophysiological studies showed
      typical features of demyelinating neuropathy with conduction blocks. Biological
      investigations, especially CMV and Campylobacter jejuni serologies, were all
      negative. Intravenous immunoglobulin infusions, in one case associated with high
      doses of corticosteroids, were ineffective. Rapid improvement was observed in the
      two patients after delivery. CONCLUSION: These cases raise the question of the
      relationships between the Guillain-Barre syndrome and pregnancy. The occurrence
      of the disease, as well as the rapid recovery in post-partum, could be
      consecutive to a partial failure of the maternal immunological tolerance toward
      the fetus.

PMID- 16585892
TI  - [Subthalamic stimulation in a patient with multiple system atrophy: a
      clinicopathological report].
AB  - INTRODUCTION: Efficacy of high frequency subthalamic nucleus (STN) stimulation
      has been demonstrated in idiopathic Parkinson's disease (IPD). However, since it
      may be difficult to differentiate IPD from multiple system atrophy with
      parkinsonian presentation (MSA-P), a few cases of MSA-P has been treated by deep
      brain stimulation (DBS) and showed no sustained improvement of clinical signs. We
      report a patient with a clinical misdiagnosed MSA-P, later confirmed by
      neuropathological study, who was improved by DBS for one year. CASE REPORT: A 63
      year-old parkinsonian patient had been treated by levodopa for 6 years with a
      persistent good response. Over one year he progressively developed disabling
      fluctuations with severe axial syndrome and vegetative non motor symptoms in off
      periods. After checking usual contraindications, he was included in surgical
      procedure protocol (bilateral STN stimulation). During the first year after
      surgery, the clinical status improved with disappearance of non motor
      fluctuations, a 45 percent decrease of the OFF UPDRS III score, and a 39 percent
      reduction of the treatment. However after one year, axial symptoms reappeared
      with recurrent falls, as well as increasing dysarthry and swallowing difficulties
      which were only slightly improved by levodopa. He developed severe urinary
      disorders increased by a prostatic adenoma which led to surgical treatment.
      During the post operative period, 2 years after DBS, he died suddenly from an
      unexplained cause. A cerebral autopsy was performed and showed a good position of
      the two electrodes in the STN. Microscopic studies revealed severe neuronal
      depletion in the substantia nigra but no Lewy bodies. Immunohistochemical methods
      demonstrated numerous argyrophilic glial cytoplasmic inclusions positive for
      alpha-synuclein and ubiquitin in the STN, putamen, globus pallidus, pontine
      nuclei and cerebellar white matter, significant of MSA. CONCLUSION: This case
      shows that DBS can improve parkinsonian signs in MSA-P with persistent dopa
      sensitivity. However, probably because of striatal degeneration progression, this
      improvement is time limited and STN DBS cannot be recommended in MSA.

PMID- 16585893
TI  - [Dorsal medulla oblongata stroke after a wasp sting].
AB  - INTRODUCTION: Although wasp stings can cause local reactions such as pain, flare,
      edema, swelling and severe reactions, including anaphylaxis; neurological
      vascular complications are rare. CASE REPORT: We report a case of a 36-year-old
      male who developed focal neurological symptoms after a wasp sting. The brain MRI
      showed an infarct in the left dorsal medulla. The blood test has showed an
      elevated level of venom-specific IgE antibodies and the skin test with wasp venom
      was highly positive. Improvement occurred rapidly after treatment with
      methylprednisone. The postulated mechanisms include vasoconstriction and platelet
      aggregation secondary to an injection of distinct allergens contained in wasp
      venom. CONCLUSION: It would thus be important to ask patients about any recent
      wasp sting, in order to provide appropriate treatment.

PMID- 16585894
TI  - [A case of neuropathy mimicking Guillain-Barre syndrome after arsenic
      intoxication].
AB  - INTRODUCTION: Chronic arsenic toxicity is a global health problem affecting
      millions of people. Acute arsenic poisoning is less frequent and it is most often
      lethal. Therefore, its consequences are not well known, more precisely its
      neurological consequences. OBSERVATION: We report a case of Guillain-Barre-like
      syndrome and encephalopathy after acute arsenical poisoning in a 50 year-old man.
      After 4 month follow-up, the improvement was slow and limited with persistent
      motor and proprioceptive deficits. DISCUSSION: The most frequent neurological
      complication induced by acute arsenical poisoning is a distal, symmetrical,
      sensory, axonal polyneuropathy. Yet the clinical course and the
      electrophysiological findings may also suggest a Guillain-Barre like syndrome.
      Moreover, the chelating is not very effective on the neurological complications.
      CONCLUSION: Any discrepancies in the clinical course of a Guillain-Barre syndrome
      shall lead to reconsider the diagnosis. The association of gastro-intestinal
      disorders, skin lesions, and encephalopathy and mood disorders leads to discuss
      intoxication with heavy metal and more precisely with arsenic. Moreover, the
      chelating is not very effective on the neurological complications.

PMID- 16585895
TI  - [Pupil-sparing painful oculomotor neuropathy due to a carotico-cavernous
      aneurysm].
AB  - INTRODUCTION: In third cranial nerve palsy, the lack of mydriasis evokes a
      noncompressive mechanism. Case report. We report a case of a slightly painful,
      pure extrinsic third-nerve palsy, complete except for the partial ptosis
      secondary to the compression by an intracavernous carotid aneurysm. Percutaneous
      endovascular embolization was followed by complete regression of the palsy within
      4 weeks. The pupil may have been spared by the mechanism of compression after the
      separation of the pupillomotor and extrinsic fibers or the ischemia of the third
      nerve by its arterial trunk lesion. CONCLUSION: This case report underlines that
      brain radiological explorations are necessary in some third-nerve pupil-sparing
      palsies.

PMID- 16585898
TI  - [Subacute deterioration of imbalance associated with headaches in an 81-year-old
      male].

PMID- 16585899
TI  - [Neurological basis of the emotional dimension of pain].
AB  - Feeling pain is in the same time a sensory and an affective experience. Pain
      asymbolia and prefrontal lobotomy, two distinct neurological pictures, help to
      better understand the cerebral basis of the emotional dimension of pain. In pain
      asymbolia, the selective alteration of the affective dimension of pain is
      associated with a loss of the sense of threat and danger. Following prefrontal
      lobotomy, the emotional impact of chronic pain is dramatically reduced, while
      affective responses to acute pain are paradoxically increased. Such clinical
      observations allow to make a clear distinction between immediate pain
      unpleasantness on the one hand, and secondary pain affect, linked to the
      significance of the pain experience in terms of the self and of the future, on
      the other hand. Moreover, recent functional neuroimaging data allow to better
      define the neural substrates of the affective dimension of pain and to highlight
      the shared neuro-anatomical networks between physical and psychic suffering.

PMID- 16585900
TI  - [A history of the controversy between Charcot and Bouchard on the subject of
      miliary aneurysms].

PMID- 16585901
TI  - [Proceedings of the XVII Neuromuscular Meeting, Marseille, France, 22-23
      September 2005].

PMID- 16585904
TI  - [Neuromuscular disorders - assessment of the respiratory muscles].
AB  - Involvement of respiratory muscles is a nearly constant feature of neuromuscular
      disorders, leading to respiratory failure. A careful respiratory follow up
      adapted to the variable time course of each disease is therefore mandatory. As
      the first step, a systematic clinical evaluation is essential to detect the
      subtle respiratory symptoms and signs related to respiratory muscle failure.
      Dyspnea and orthopnea are often late findings in patients with a usually severe
      functional impairment due to peripheral muscle weakness. Nocturnal respiratory
      events (obstructive sleep apnea syndrome and hypoventilation) are strongly
      suggested by daytime hypersomnolence and frequent morning headaches. Physical
      evaluation is essential to detect accessory muscle recruitment, supine abdominal
      paradox, and encumbrance of upper or lower airways. Vital capacity (VC) is the
      most classical lung function test. The major limitation of spirometry is its poor
      sensitivity to detect a moderate inspiratory muscle weakness. Supine VC may
      improve the detection of diaphragmatic involvement. Peak expiratory flow during
      cough (cough PEF) gives an overall evaluation of cough efficiency, values below
      160 to 270 L/min suggesting poor airway clearance. Arterial blood gases are
      performed in case of clinical signs, significant deterioration of lung function
      tests, or sleep desaturations. Hypercapnia is weakly related to lung function
      results in patients with Steinert dystrophy and those with bulbar involvement. A
      specific evaluation of respiratory muscle strength is mandatory, as these tests
      are both sensitive and highly prognostic. Possible discrepancies (particularly in
      bulbar patients) between maximal inspiratory pressure (PImax) and sniff nasal
      inspiratory pressure (SNIP) justify to perform both measurements and to select
      the highest pressure. A maximal expiratory pressure (PEmax) below 45 cm H2O may
      indicate a compromised cough efficiency but the correlation with cough PEF may be
      poor. A screening nocturnal oxymetry is useful to detect sleep apneas and
      hypoventilation. Criteria defining significant desaturations remain however
      controversial. Suspicion of obstructive sleep apnea syndrome on clinical grounds
      or oxymetry findings should be confirmed by a conventional polysomnography.

PMID- 16585903
TI  - [Manual and quantitative muscle testing in neuromuscular disorders. How to assess
      the consistency of strength measurements in clinical trials?].
AB  - Evaluation of functional capacities of patients suffering of neuromuscular
      disorders, particularly muscle strength, is a critical issue for their diagnosis
      and follow-up. Within the framework of the natural history of any given disease,
      such an evaluation may improve the clinician's knowledge of the
      pathophysiological processes involved, and may help to anticipate and sometimes
      prevent deleterious consequences as the disease progresses. It is also helpful
      for identifying correlation between the severity of organic damage and the
      functional impact of the disease. The measurement of functional capacities must
      be done with accuracy, sensitivity and reliability, essentially when used as an
      outcome measure for therapeutic trials. Several evaluation tools for measuring
      muscle strength are available. They are usually classified into two groups:
      manual muscle testing (MMT) methods and quantified muscle testing (QMT) methods.
      In this article, we present the principles of strength measurements, and the
      different tools and materials that are commonly used in clinical settings. Their
      limitations and drawbacks are illustrated through several examples. Although QMT
      is theoretically and potentially more consistent than MMT to precisely follow the
      muscle capacities of the patients, precise and robust procedures must be
      elaborated and validated for each tested muscle function. Strength measurements
      must be performed by trained and experimented clinical evaluators. This issue is
      critical in the follow up of multicentric therapeutic trials. Inter-rater
      reliability must be assessed to guarantee the statistical power of the trial.

PMID- 16585905
TI  - [Assessment of dysarthria and dysphagia in ALS patients].
AB  - Swallowing and speech disorders are the dramatic consequences of bulbar and
      pseudo-bulbar syndrome in ALS. Evaluation is necessary to guide speech therapy
      and to measure the effects of treatment. This article revues the different
      examinations used to assess bulbar and pseudobulbar involvement in an ALS
      patient: oromotor assessment, evaluation of the functions with self assessment,
      perceptive and objective evaluation of speech disorders, fiberoptic endoscopic
      evaluation of dysphagia (FEES) and videofluoroscopy.

PMID- 16585906
TI  - [Therapeutic trials and muscular diseases].
AB  - Recent advances in knowledge of muscle diseases has opened new perspectives for
      clinical trials. Because of the small number of patients available for study and
      the requirement for homogeneous study groups, multicentric trials must be
      conducted on a national or international basis. Moreover, because of the
      variability of clinical course of muscle diseases therapeutic protocols must be
      preceded by an assessment of the natural history of the disease. Analytic methods
      available include manual testing, quantitative muscle testing (QMT), functional
      scales, and evaluation of cardiac and respiratory function. Based on experience
      acquired with earlier protocols, we present methodologies currently used and the
      difficulties encountered. We discuss the potential ways for improving therapeutic
      trials.

PMID- 16585907
TI  - [Assessment of muscle function in pathology with surface electrode EMG].
AB  - Surface electromyography (SEMG) had been and is still widely used in kinesiology
      and fatigue studies. Its use in routine clinical neurophysiology remains limited.
      Patients are requiring non-invasive EMG, which could also benefit to physicians
      and health care system looking for tools to evaluate muscle function in
      neuromuscular diseases as well as for therapeutic trials. This is the aim of our
      clinical studies. We apply SEMG envelope signal analysis acquired from maximal
      voluntary contractions, and the related compound muscle action potential (CMAP).
      These unspecific parameters cannot be used for neuromuscular diseases diagnosis,
      objective under study by many research teams. In nerve lesions follow-up studies,
      our SEMG procedure is related to motor clinical progression. We are currently
      evaluating it in chronic neuromuscular diseases. The respective contribution in
      neuromuscular disorders of the different neurophysiology techniques has still to
      be confirmed, and compared to force measurement by manual or quantitative
      testing, dynamometry, other suggested techniques (spectroscopy, imaging) as well
      as functional scales.

PMID- 16585909
TI  - [A motor function measurement scale for neuromuscular diseases - description and
      validation study].
AB  - A new scale for motor function measurement has been developed for neuromuscular
      diseases. After the study of a preliminary and a first version, the validation
      study included 303 patients, aged 6 to 62 years. Seventy-two patients had
      Duchenne muscular dystrophy, 32 Becker muscular dystrophy, 30 limb-girdle
      muscular dystrophy, 39 facio-scapulo-humeral dystrophy, 29 myotonic dystrophy, 21
      congenital myopathy, 10 congenital muscular dystrophy, 35 spinal muscular atrophy
      and 35 hereditary neuropathy. The sensitivity for change was evaluated with 152
      patients one year after. The scale comprised 32 items, in three dimensions:
      standing position and transfers, axial and proximal motor function, distal motor
      function. High correlations (>0.80) were found between the total score and other
      scores: Vignos and Brooke grades, Functional Independence Measure, the global
      severity of disability evaluated with visual analog scales by physicians and
      physiotherapists. This scale is reliable, does not require any special equipment
      and is well accepted by patients. It takes an average of 36 min (range 8-75) to
      complete the scale. Preliminary results of the second evaluation showed good
      sensitivity to change since last visit, considering rating by patient,
      investigator or physiotherapist. Also, significant differences in scores are
      obtained with the greatest deterioration observed in Duchenne patients.

PMID- 16585910
TI  - [Dysimmune peripheral neuropathies].
AB  - The usefulness of functional scales has become clear in the past few years, to
      evaluate patients with dysimmune peripheral neuropathies. Functional scales which
      measure the real impact of the disease process in our patients will probably be
      increasingly used in future therapeutic trials. By contrast with neurological
      disorders leading to pure motor involvement, peripheral neuropathies are
      difficult to evaluate, due to their clinical polymorphism. However, efforts have
      been made in the past ten years in order to validate functional scales that may
      be routinely used by neurologists for dysimmune neuropathies. New scales will
      probably arise in the next few years, to be used in neuropathies from other
      causes. These scales will have to be strictly validated to be used in the daily
      medical practice.

PMID- 16585908
TI  - [Non-invasive investigation of muscle function using 31P magnetic resonance
      spectroscopy and 1H MR imaging].
AB  - 31P MRS and 1H MRI of skeletal muscle have become major new tools allowing a
      complete non invasive investigation of muscle function both in the clinical
      setting and in basic research. The comparative analysis of normal and diseased
      muscle remains a major requirement to further define metabolic events surrounding
      muscle contraction and the metabolic anomalies underlying pathologies. Also,
      standardized rest-exercise-recovery protocols for the exploration of muscle
      metabolism by P-31 MRS in healthy volunteers as well as in patients with
      intolerance to exercise have been developed. The CRMBM protocol is based on a
      short-term intense exercise, which is very informative and well accepted by
      volunteers and patients. Invariant metabolic parameters have been defined to
      characterize the normal metabolic response to the protocol. Deviations from
      normality can be directly interpreted in terms of specific pathologies in some
      favorable cases. This protocol has been applied to more than 4,000 patients and
      healthy volunteers over a period of 15 years. On the other hand, MRI
      investigations provide anatomical and functional information from resting and
      exercising muscle. From a diagnostic point of view, dedicated pulse sequences can
      be used in order to detect and quantify muscle inflammation, fatty replacement,
      muscle hyper and hypotrophy. In most cases, MR techniques provide valuable
      information which has to be processed in conjunction with traditional invasive
      biochemical, electrophysiological and histoenzymological tests. P-31 MRS has
      proved particularly useful in the therapeutic follow-up of palliative therapies
      (coenzyme Q treatment of mitochondriopathies) and in family investigations. It is
      now an accepted diagnostic tool in the array of tests which are used to
      characterize muscle disorders in clinical routine. As a research tool, it will
      keep bringing new information on the physiopathology of muscle diseases in animal
      models and in humans and should play a role in the metabolic characterization of
      gene and cell therapy.

PMID- 16585911
TI  - [Functional rating scales for amyotrophic lateral sclerosis].
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of the
      peripheral and central motor neurons. The principal consequence is a loss of
      motor functions. Evaluation of motor deficit implies an assessment of the
      resulting deficiency or incapacity and final disability. Many evaluation are
      proposed for patient follow-up in order to analyze the state of motor function
      and their consequences on activities of everyday life. Few recommendations can be
      formulated. Scales must be validated and relatively simple to use and generate
      ordinate results allowing statistical analysis. The choice of which scale to use
      depends on the clinical objective. Global scales (ALS Functional rating Scale,
      ALS Severity Scale, Appel scale, Norris scale and Honda scale) can be used to
      evaluate progression of the disability. Some of these scales are strongly
      correlated with patient survival. Other scales (ALS Health State Scale, global
      clinical impression) are used to classify patients by homogeneous stage of
      gravity. Still other scales, such as the Sadoul and Borg scales and the Epworth
      score are designed for more specific evaluation of a given function. The
      clinician should be aware of these different scales and their relative utility.
      Knowledge of these scales, their validity, their sensitivity to modification, and
      their specificity and interpretation pitfalls is a prerequisite to good
      evaluation in daily practice and clinical research.

PMID- 16585912
TI  - [Quality of life measurement: a fashion or a valid assessment?].
AB  - During 20 last years, there has been an exponential growth in the literature
      related to quality of life (QoL). The usual indicators of results are not always
      responsive to new strategies or new systems of care organization. While
      assessment of QoL by patients and by the medical community is an old concern, the
      issue of standardized instruments is more recent. Despite the need, the use of
      QoL questionnaires remains rare because of the lack of sufficiently dedicated
      tools. In the specific field of motoneuron diseases, a search of the literature
      should be helpful to clarify the definition of quality of life. It should also be
      helpful in determining the limits of the debate on quantification of an
      impression considered to be subjective. The goal is to clarify methods for
      standardizing QoL evaluation, to specify nosographic notions affecting the choice
      of measuring instruments, to recall the prerequisite of validation before use,
      and finally to specify the fields of application of such tools. Thus in the field
      of motoneuron diseases, recognizing the limitations of QoL instruments should
      enable a more enlightened approach to overall assessment of the burden of these
      diseases.

PMID- 16585913
TI  - [Historical evolution of the concept of chronic polyradiculoneuropathy].

PMID- 16585914
TI  - [The extent of the clinical manifestations of chronic polyradiculoneuropathy].
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy is an
      autoimmune disease that target myelin sheats of peripheral nerves. Its diagnosis
      is often difficult to make, and a number of cases are probably not identified
      because of the clinical heterogeneity. Numerous sets of diagnostic criteria have
      sought to define CIDP but clinical criteria are generally not detailed.
      OBJECTIVES: To review the main clinical characteristics suggestive of CIDP (that
      means not compatible with a length-dependent axonal process) and the critical
      clinical points of the neuropathy which make the differential diagnosis with the
      main other forms of chronic auto immune neuropathy sometimes difficult. RESULTS:
      The main clinical characteristic are: a symmetric proximal and distal motor
      weakness predominantly affecting the lower limbs, a diffuse areflexia, a sensory
      deficit characterized by a preferential involvement of large fibers, an evolution
      which may be either chronic progressive or recurrent. These aspects raise many
      questions concerning overlap with other inflammatory neuropathies such as
      Guillain Barre syndrome, Lewis-Sumner neuropathy, chronic ataxic neuropathy. The
      distinction of a subgroup of CIDP associated with other diseases such as diabetes
      or HIV are also controversial. CONCLUSION: The growing body of knowledge on the
      pathogenesis of CIDP and clinical or electrophysiological differentiation of
      subforms may help to develop more effective therapies for CIDP in the next few
      years.

PMID- 16585915
TI  - [Electrophysiological manifestations of chronic inflammatory demyelinating
      polyradiculoneuropathy].
AB  - There are four basic electrophysiological parameters of demyelination: reduced
      motor conduction velocity, prolonged distal motor latency and F waves, and motor
      conduction blocks. These parameters are combined to determine an
      electrophysiological set of criteria for chronic inflammatory demyelinating
      polyneuropathy (CIDP). Whereas their specificity is good, their sensitivity level
      does not exceed 75 percent. However, these sets of criteria are not commonly used
      especially in benign forms, at the beginning of the disease, in associated forms
      or in case of secondary axonal degeneration. We can push the limits using others
      criteria such as the terminal latency index, sensory criteria, or by the
      contribution of others electrophysiological procedures such as the radicular
      stimulation or sensory evoked potentials. Due to the therapeutic implications,
      any axonal neuropathy without aetiologia, with at least one demyelinating
      electrophysiological criteria, could be considered as a putative CIDP.

PMID- 16585916
TI  - [Histopathological features of chronic inflammatory demyelinating
      polyradiculoneuropathy].
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) was proposed by Dyck et
      al. in 1975. Diagnosis was based mainly on nerve biopsy features with segmental
      demyelination, onion bulb formation and inflammatory infiltrates. In many
      pathological studies, frequencies of these features of CIDP were not observed in
      the same percentages. Limitations on the nerve biopsy were explained by the study
      of small, distal, only sensory nerve specimens in the lower limb. In recent
      years, the usefulness of nerve biopsy has been reconsidered. If electron
      microscopy and teased-fiber studies are used, the examination can recognize CIDP
      erroneously classified as chronic idiopathic axonal polyneuropathy. Therapeutic
      options should be guided by suggestive abnormalities of demyelination and or
      inflammation on nerve biopsy even in the presence of a electrophysiologic axonal
      pattern.

PMID- 16585917
TI  - [Biochemical features of chronic inflammatory demyelinating
      polyradiculoneuropathy].
AB  - Although there are no specific biological markers of chronic inflammatory
      demyelinating polyneuropathies (CIDP), biological investigations have played an
      important role in determining the limits of the concept of CIDP. This is best
      exemplified by the individualisation of demyelinating neuropathies associated
      with IgM monoclonal proteins reacting with glycolipids. The signification of CIDP
      associated with diabetes mellitus, monoclonal IgG or IgA, or mutations of myelin
      proteins has recently been discussed as they may have implications in our
      understanding of the pathophysiology of CIDP and raise the question of knowing
      whether they confer to CIDP a particular clinical presentation or evolution.

PMID- 16585918
TI  - [Treatment options for chronic inflammatory demyelinating polyradiculoneuropathy
      (CIDP)].
AB  - Limits of treatment in chronic inflammatory demyelinating
      poly(radiculo)neuropathies (CIDP) patients are better known thanks to recent
      Cochrane reviews. (1) Randomized controlled trials have only focused on short
      term effects, but most patients need long-term therapy, (2) There are three
      proven effective treatments available (prednisone; intravenous immunoglobulin or
      IVIg and plasma exchange or PE) which are useful in more than 60 p. 100 of
      patients, (3) New open studies indicated possible efficacy for mycophenolate,
      rituximab, etanercept, ciclosporine and interferons, and (4) Whether CIDP
      variants need specific treatment is still unknown. Many CIDP patients need
      treatment for years. The fear of side effects during long-term steroid treatment,
      the high costs of IVIg, the necessity for specialized equipment and the invasive
      nature of PE, are important factors determining the choice for one of these
      treatments. In most up-to-date treatment options, patients are initially treated
      with IVIg at a dosage of 2 g/kg administered for 25 days, clinical improvement
      can be judged within 10 days. The percentage of patients responding seems to be
      approximately 70 percent, with a very high chance (approximately 85 percent) that
      repeated administration of IVIg will be necessary, explaining why most
      neurologists add an immunosuppressive drug at this stage, but there is no
      consensus concerning the best drug to be used. Combinations of drugs are most
      likely to be useful in the next future, using IVIg, prednisone, and a
      immunosuppressor agent, such as mycophenolate, rituximab, etanercept, or
      ciclosporine. General measures to rehabilitate patients and to manage symptoms
      like fatigue and other residual findings are important.

PMID- 16585919
TI  - [Case management of amyotrophic lateral sclerosis patients. Consensus development
      conference, Nice, France, 23-24 November 2005. French Neurology Society.
      Association of Independent French-speaking Neurologists].

PMID- 16585920
TI  - Breast imaging. Picturing the latest breast cancer detection methods.

PMID- 16585921
TI  - Alcohol use, with hormone therapy, may increase breast cancer risk.

PMID- 16585922
TI  - Heart may benefit from replacing some carbohydrates with protein.

PMID- 16585923
TI  - Drinking tea every day reported to reduce ovarian cancer risk.

PMID- 16585924
TI  - Treating uterine fibroids. New therapies provide more choices.

PMID- 16585926
TI  - Mayo Clinic office visit. What's new with hormone therapy? An interview with
      Julie Abbott, M.D., M.P.H., and Lynne Shuster, M.D.

PMID- 16585925
TI  - Human papillomavirus. A major cause of cervical cancer.

PMID- 16585927
TI  - Eating less and often. Does it help weight control?

PMID- 16585928
TI  - How can I avoid getting diarrhea while traveling abroad?

PMID- 16585929
TI  - Are there any health risks to not washing new clothes before wearing them?

PMID- 16585930
TI  - I love milk, but I notice that as I get older I seem to tolerate it less-
      experiencing gas and bloating. Is this normal?

PMID- 16585931
TI  - Life science infrastructures are different.

PMID- 16585932
TI  - Cell 'guidling'.

PMID- 16585933
TI  - All the evidence.

PMID- 16585934
TI  - Bioethics for the world.

PMID- 16585935
TI  - Mind-body research moves towards the mainstream.

PMID- 16585938
TI  - A Bex-cycle built for two.

PMID- 16585939
TI  - Psychrophilic microorganisms: challenges for life.
AB  - The ability of psychrophiles to survive and proliferate at low temperatures
      implies that they have overcome key barriers inherent to permanently cold
      environments. These challenges include: reduced enzyme activity; decreased
      membrane fluidity; altered transport of nutrients and waste products; decreased
      rates of transcription, translation and cell division; protein cold-denaturation;
      inappropriate protein folding; and intracellular ice formation. Cold-adapted
      organisms have successfully evolved features, genotypic and/or phenotypic, to
      surmount the negative effects of low temperatures and to enable growth in these
      extreme environments. In this review, we discuss the current knowledge of these
      adaptations as gained from extensive biochemical and biophysical studies and also
      from genomics and proteomics.

PMID- 16585941
TI  - Glucose enhances mesangial cell apoptosis.
AB  - Mesangial cell apoptosis occurs in experimental diabetic nephropathy, and this
      correlates with worsening albuminuria. This study examines the mechanism by which
      glucose modulates mesangial cell apoptosis. Apoptosis was induced in mesangial
      cells by serum deprivation in the presence of 5 or 25 mM D-glucose, and examined
      by expression of Annexin-V and disruption of mitochondrial transmembrane
      potential. Involvement of Bax, Bcl-2 and NF-kappaB were examined by RT-PCR and
      EMSA. Involvement of TGF-beta1 was sought by determining the effect of
      recombinant TGF-beta1on apoptosis and the mediators of the apoptotic pathway
      (Bcl2/Bax and NF-kappaB). Culture of cells in the presence of 25 mM D-glucose (i)
      enhanced apoptosis stimulated by serum depletion, (ii) enhanced activation of
      caspase-3, (iii) inhibited NF-kappaB activation, and (iv) decreased Bcl-2:Bax
      ratio. Inhibition of NF-kappaB using SN50, also increased mesangial cell
      apoptosis, and decreased Bcl-2:Bax ratio. Addition of TGF-beta1 to mesangial
      cells mimicked the effect of high glucose reducing NF-kappaB expression and Bcl
      2:Bax ratio. Furthermore glucose-mediated enhanced apoptosis was inhibited by the
      addition of a blocking antibody to TGF-beta1. Exposure of mesangial cells to 25
      mM D-glucose stimulated the generation of both total and active TGF-beta1 in the
      cell culture supernatant, this increase was only significant after 48-72 h, that
      is at a time point later than enhanced apoptosis. Addition of 25 mM D-glucose,
      however, increased sensitivity of mesangial cells to TGF-beta1 as assessed by
      luciferase activity of a Smad sensitive reporter construct. The data suggest that
      elevated glucose concentration enhanced the pathway leading to apoptosis
      following serum deprivation. Furthermore, it is likely that this is dependent on
      glucose-mediated enhanced sensitivity to endogenous TGF-beta1 rather than glucose
      stimulated de novo TGF-beta1 synthesis.

PMID- 16585943
TI  - The role of phospholipases A2 in schizophrenia.
AB  - A range of neurotransmitter systems have been implicated in the pathogenesis of
      schizophrenia based on the antidopaminergic activities of antipsychotic
      medications, and chemicals that can induce psychotic-like symptoms, such as
      ketamine or PCP. Such neurotransmitter systems often mediate their cellular
      response via G-protein-coupled release of arachidonic acid (AA) via the
      activation of phospholipases A2 (PLA2s). The interaction of three PLA2s are
      important for the regulation of the release of AA--phospholipase A2 Group 2 A,
      phospholipase A2 Group 4A and phospholipase A2 Group 6A. Gene variations of these
      three key enzymes have been associated with schizophrenia with conflicting
      results. Preclinical data suggest that the activity of these three enzymes are
      associated with monoaminergic neurotransmission, and may contribute to the
      differential efficacy of antipsychotic medications, as well as other biological
      changes thought to underlie schizophrenia, such as altered neurodevelopment and
      synaptic remodelling. We review the evidence and discuss the potential roles of
      these three key enzymes for schizophrenia with particular emphasis on published
      association studies.

PMID- 16585942
TI  - A systematic review: antipsychotic augmentation with treatment refractory
      obsessive-compulsive disorder.
AB  - As many as half of obsessive-compulsive disorder (OCD) patients treated with an
      adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to
      treatment and continue to exhibit significant symptoms. Many studies have
      assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD.
      In this systematic review, we evaluate the efficacy of antipsychotic augmentation
      in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967
      2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials
      (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials
      using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive
      disorder'. Search results and analysis were limited to double-blind, randomized
      control trials involving the adult population. The proportion of subjects
      designated as treatment responders was defined by a greater than 35% reduction in
      Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of
      augmentation therapy. Nine studies involving 278 participants were included in
      the analysis. The meta-analysis of these studies demonstrated a significant
      absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22
      (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with
      comorbid tics have a particularly beneficial response to this intervention,
      ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients
      should be treated with at least 3 months of maximal-tolerated therapy of an SRI
      before initiating antipsychotic augmentation owing to the high rate of treatment
      response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI
      refractory OCD is indicated in patients who have been treated for at least 3
      months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of
      treatment-refractory OCD patients show a meaningful treatment response to
      antipsychotic augmentation. There is sufficient evidence in the published
      literature, demonstrating the efficacy of haloperidol and risperidone, and
      evidence regarding the efficacy of quetiapine and olanzapine is inconclusive.
      Patients with comorbid tics are likely to have a differential benefit to
      antipsychotic augmentation.

PMID- 16585944
TI  - Behavioural food labelling.

PMID- 16585945
TI  - Content comparison of health status measures for obesity based on the
      international classification of functioning, disability and health.
AB  - OBJECTIVE: To compare the content covered by twelve obesity-specific health
      status measures using the International Classification of Functioning, Disability
      and Health (ICF). DESIGN: Obesity-specific health status measures were identified
      and then linked to the ICF separately by two trained health professionals
      according to standardized guidelines. The degree of agreement between health
      professionals was calculated by means of the kappa (kappa) statistic.
      Bootstrapped confidence intervals (CI) were calculated. The obesity-specific
      health-status measures were compared on the component and category level of the
      ICF. MEASUREMENTS: welve condition-specific health-status measures were
      identified and included in this study, namely the obesity-related problem scale,
      the obesity eating problems scale, the obesity-related coping and obesity-related
      distress questionnaire, the impact of weight on quality of life questionnaire
      (short version), the health-related quality of life questionnaire, the obesity
      adjustment survey (short form), the short specific quality of life scale, the
      obesity-related well-being questionnaire, the bariatric analysis and reporting
      outcome system, the bariatric quality of life index, the obesity and weight loss
      quality of life questionnaire and the weight-related symptom measure. RESULTS: In
      the 280 items of the eight measures, a total of 413 concepts were identified and
      linked to the 87 different ICF categories. The measures varied strongly in the
      number of concepts contained and the number of ICF categories used to map these
      concepts. Items on body functions varied form 12% in the obesity-related problem
      scale to 95% in the weight-related symptom measure. The estimated kappa
      coefficients ranged between 0.79 (CI: 0.72, 0.86) at the component ICFs level and
      0.97 (CI: 0.93, 1.0) at the third ICF's level. CONCLUSION: The ICF proved highly
      useful for the content comparison of obesity-specific health-status measures. The
      results may provide clinicians and researchers with new insights when selecting
      health-status measures for clinical studies in obesity.

PMID- 16585946
TI  - Genetic variation at the perilipin locus is associated with changes in serum free
      fatty acids and abdominal fat following mild weight loss.
AB  - OBJECTIVE: Perilipin (PLIN) is a class of protein-coating lipid droplets in
      adipocytes. We aimed to examine the association between common single-nucleotide
      polymorphisms (SNPs) at PLIN locus with circulating free fatty acid (FFA) and
      abdominal fat distribution in response to weight loss. METHODS: Non
      diabetic/overweight-obese Koreans (n=177) participated in a 12-week calorie
      restriction (-300kcal/day) program. Seven SNPs (6209T>C, 10076C>G, 10171A>T,
      11482G>A, 13042A>G, 13048C>T and 14995A>T), abdominal fat areas
      (visceral/subcutaneous fat areas at 1st lumbar and 4th lumbar levels), serum
      lipids, glucose, insulin, FFA, oxidized low-density lipoprotein (LDL) and urinary
      8-epi-prostaglandin F(2alpha) (PGF(2alpha)) were examined. RESULTS: Single
      nucleotide polymorphisms 10076C>G/10171A>T showed the strongest positive linkage
      disequilibrium (LD) (D'=0.923, R (2)=0.839, P<0.001) and SNPs11482G>A/14995A>T
      showed moderate positive LD (D'=0.824, R (2)=0.578, P<0.001). Calorie restriction
      induced 4.6% weight loss with significant abdominal fat reduction. In response to
      weight loss, subjects with nCA/nCA haplotypes at SNPs 10076C>G/10171A>T showed
      greater reduction in FFA levels than those with CA/CA haplotype (CA/CA: C/C at
      SNP 10076 and A/A at SNP 10171, nCA: non-CA haplotype carrier). On the other
      hand, subjects with nGA/nGA haplotype at SNPs 11482G>A/14995A>T had increased FFA
      levels with a rapid loss in abdominal fat, whereas GA/GA haplotype carriers had
      reduction in FFA levels. These results still remained significant after adjusting
      for age, gender and BMI. Prostaglandin F(2alpha) and oxidized LDL were also more
      reduced in GA/GA haplotype carriers than in nGA haplotype carriers. This effect
      remained significant after adjusting for baseline level, age, gender and BMI.
      Paradoxically, nGA haplotype carriers had increased levels of urinary PGF(2alpha)
      after weight reduction. CONCLUSION: Fasting plasma FFA changes following a modest
      weight loss in overweight-obese subjects are influenced by the genetic
      variability at the PLIN locus. Furthermore, circulating FFA changes rather than
      body fat itself may determine changes in lipid peroxides such as urinary
      PGF(2alpha) and oxidized LDL.

PMID- 16585947
TI  - Dephosphorylation specificities of protein phosphatase for cardiac troponin I,
      troponin T, and sites within troponin T.
AB  - Protein dephosphorylation by protein phosphatase 1 (PP1), acting in concert with
      protein kinase C (PKC) and protein kinase A (PKA), is a pivotal regulatory
      mechanism of protein phosphorylation. Isolated rat cardiac myofibrils
      phosphorylated by PKC/PKA and dephosphorylated by PP1 were used in determining
      dephosphorylation specificities, Ca(2+)-stimulated Mg(2+)ATPase activities, and
      Ca(2+) sensitivities. In reconstituted troponin (Tn) complex, PP1 displayed
      distinct substrate specificity in dephosphorylation of TnT preferentially to TnI,
      in vitro. In situ phosphorylation of cardiomyocytes with calyculin A, a protein
      phosphatase inhibitor, resulted in an increase in the phosphorylation
      stiochiometry of TnT (0.3 to 0.5 (67%)), TnI (2.6 to 3.6 (38%)), and MLC2 (0.4 to
      1.7 (325%)). These results further confirmed that though MLC2 is the preferred
      target substrate for protein phosphatase in the thick filament, the Tn complex
      (TnI and TnT) from thin filament and C-protein in the thick filament are also
      protein phosphatase substrates. Our in vitro dephosphorylation experiments
      revealed that while PP1 differentially dephosphorylated within TnT at multiple
      sites, TnI was uniformly dephosphorylated. Phosphopeptide maps from the in vitro
      experiments show that TnT phosphopeptides at spots 4A and 4B are much more
      resistant to PP1 dephosphorylation than other TnT phosphopeptides. Mg(2+)ATPase
      assays of myofibrils phosphorylated by PKC/PKA and dephosphorylated by PP1
      delineated that while PKC and PKA phosphorylation decreased the Ca(2+)-stimulated
      Mg(2+)ATPase activities, dephosphorylation antagonistically restored it. PKC and
      PKA phosphorylation decreased Ca(2+) sensitivity to 3.6 microM and 5.0 microM
      respectively. However, dephosphorylation restored the Mg(2+)ATPase activity of
      PKC (99%) and PKA (95%), along with the Ca(2+) sensitivities (3.3 microM and 3.0
      microM, respectively).

PMID- 16585948
TI  - NAD(H) recycling activity of an engineered bifunctional enzyme galactose
      dehydrogenase/lactate dehydrogenase.
AB  - A chimeric bifunctional enzyme composing of galactose dehydrogenase (galDH; from
      Pseudomonas fluorescens) and lactate dehydrogenase (LDH; from Bacillus
      stearothermophilus) was successfully constructed. The chimeric galDH/LDH
      possessed dual characteristics of both galactose dehydrogenase and lactate
      dehydrogenase activities while exhibiting hexameric rearrangement with a
      molecular weight of approximately 400 kDa. In vitro observations showed that the
      chimeric enzyme was able to recycle NAD with a continuous production of lactate
      without any externally added NADH. Two fold higher recycling rate (0.3 mM/h) than
      that of the native enzyme was observed at pH values above 8.5. Proximity effects
      became especially pronounced during the recycling assay when diffusion hindrance
      was induced by polyethylene glycol. All these findings open up a high feasibility
      to apply the NAD(H) recycling system for metabolic engineering purposes e.g. as a
      model to gain a better understanding on the molecular proximity process and as
      the routes for synthesizing of numerous high-value-added compounds.

PMID- 16585950
TI  - Rescuing the NIH before it is too late.
AB  - In the Coen brothers' The Big Lebowski the hero, who calls himself "The Dude,"
      has just had his apartment broken into by some dumb thugs. One of the thugs lifts
      the Dude's prized bowling ball and says, "What . . . is this?" The Dude replies,
      "Obviously you are not a golfer." The current state of the NIH prompts me to say
      to its director, Dr. Elias Zerhouni, "Obviously you are not a scientist."

PMID- 16585949
TI  - The effects of sympathectomy and dexamethasone in rats ingesting sucrose.
AB  - Both high-sucrose diet and dexamethasone (D) treatment increase plasma insulin
      and glucose levels and induce insulin resistance. We showed in a previous work
      (Franco-Colin, et al. Metabolism 2000; 49:1289-1294) that combining both
      protocols for 7 weeks induced less body weight gain in treated rats without
      affecting mean daily food intake. Since such an effect may be explained by an
      increase in caloric expenditure, possibly due to activation of the sympathetic
      nervous system by sucrose ingestion, in this work, and using 10% sucrose in the
      drinking water, male Wistar rats were divided into 4 groups. Two groups were
      sympathectomized using guanethidine (Gu) treatment for 3 weeks. One of these
      groups of rats received D in the drinking water. Of the 2 groups not receiving
      Gu, one was the control (C) and the other received D. After 8 weeks a glucose
      tolerance test was done. The rats were sacrificed and liver triglyceride (TG),
      perifemoral muscle lipid, and norepinephrine (NE) levels in the liver spleen,
      pancreas, and heart were determined. Gu-treated rats (Gu and Gu+D groups) showed
      less than 10% NE concentration compared to C and D rats, less daily caloric
      intake and body-weight gain, more sucrose intake, and better glucose tolerance.
      The area under the curve after glucose administration correlated significantly
      with the mean body weight gain of the rats, except for D group. Groups D (D and
      Gu+D) also showed less caloric intake and body-weight gain but higher liver
      weight and TG concentration and lower peripheral muscle mass. The combination of
      Gu+D treatments showed some peculiar results: negative body weight gain, a fatty
      liver, and low muscle mass. Though the glucose tolerance test had the worst
      results for the D group, it showed the best results in the Gu+D group. There were
      significant interactions for Guan X Dex by two-way ANOVA test for the area under
      the curve in the glucose tolerance test, muscle mass, and muscle lipids. The
      results suggest that dexamethasone catabolic effect is not caused by sympathetic
      activation.

PMID- 16585952
TI  - Childhood lead poisoning: the torturous path from science to policy.
AB  - The long history of lead poisoning provides many lessons about the process by
      which scientific knowledge is translated into public health policy. In the United
      States, lead was added to paint and to gasoline in enormous quantities long after
      medical evidence clearly showed that excessive lead exposure caused considerable
      morbidity in the population. This article discusses some of the factors that
      contributed to the slow pace of efforts to address this problem, including the
      ubiquity and magnitude of lead exposure during much of the twentieth century,
      which produced a distorted notion about the blood lead level that can be
      considered "normal"; the prevailing model of disease during this period, notably
      the novelty of the concept of subclinical disease; the fact that childhood lead
      poisoning affected mostly families that were politically and economically
      disenfranchised, fostering a "blame the victim" attitude; and that controlling
      lead exposure would have impeded efforts to achieve other desirable goals,
      illustrating the role that value trade-offs often play in policy decisions.

PMID- 16585951
TI  - Harnessing preclinical mouse models to inform human clinical cancer trials.
AB  - The urgent need for better cancer treatments has stimulated interest in employing
      small-animal models to evaluate potential drug therapies. Robust mouse models of
      many human cancers have been generated using sophisticated technologies for
      engineering germ-line mutations. As we enter into an age of targeted
      therapeutics, these strains provide novel platforms for validating new anticancer
      drugs, assessing therapeutic index, identifying surrogate markers of tumor
      progression, and defining epigenetic and environmental influences on
      tumorigenesis.

PMID- 16585953
TI  - Adult T cell leukemia: a tale of two T cells.
AB  - Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent for the
      development of an aggressive hematologic neoplasia termed adult T cell
      leukemia/lymphoma (ATLL). Although the virus infects T cell subsets that display
      either CD4 or CD8 cell surface markers, the leukemic cell is exclusively of the
      CD4+ subtype. In the article by Sibon et al. in this issue of the JCI, the
      authors demonstrate that the molecular basis for clonal expansion differs between
      these 2 infected T cell populations (see the related article beginning on page
      974). The molecular events associated with a preleukemic state, such as genomic
      instability, polynucleation, and cell cycle redistribution, were only observed in
      CD4+ T cells. This finding provides a molecular-based mechanism for the
      restriction of the leukemic phenotype to the CD4+ T cell subtype.

PMID- 16585954
TI  - Oxidative stress in sepsis: a redox redux.
AB  - Sepsis and sepsis syndrome are leading causes of mortality throughout the world.
      It is widely held that sepsis represents a dysregulated innate immune response to
      an offending pathogen. This immune response is often initiated via microbial
      products signaling through TLRs expressed on host immune cells. There is
      increasing evidence that this innate response can be dramatically influenced by
      the cellular redox state, and thus a better understanding of oxidative regulation
      of innate immunity could lead to new treatments for sepsis. In this issue of the
      JCI, Thimmulappa et al. show that nuclear factor-erythroid 2-related factor 2
      (Nrf2), a member of the "cap'n'collar" family of basic region-leucine zipper
      transcription factors, which has previously been shown to be involved in the
      transcription of antioxidant gene expression in response to xenobiotic stress, is
      also a critical regulator of cellular oxidative stress in sepsis (see the related
      article beginning on page 984).

PMID- 16585955
TI  - The alchemy of tendon repair: a primer for the (S)mad scientist.
AB  - During vertebrate development, mesenchymal progenitors capable of forming bone,
      cartilage, muscle, fat, or tendon arise from either neural crest or somitic
      mesoderm. Transcriptional programs that specify mesenchymal cell fates are
      initiated and modified by paracrine cues provided by TGF-beta superfamily members
      and mediated in part via the regulated assembly of Smad-containing multiprotein
      transcription factor complexes. In this issue of the JCI, Hoffmann and colleagues
      have identified that Smad8 activation drives tendon formation from C3H10T1/2
      cells, a murine cell line that recapitulates many features of normal multipotent
      mesenchymal cells (see the related article beginning on page 940). Cells
      programmed to the tenocyte cell fate in vitro formed tenogenic grafts in vivo.
      These results add to the accumulating evidence that proliferating, multipotent
      mesenchymal progenitor cells can be programmed to yield multiple cell types-
      e.g., osteoblasts, myocytes, chondrocytes, and tenocytes--that may be useful in
      cell-based therapeutic approaches to musculoskeletal diseases.

PMID- 16585956
TI  - A new cardiac MASTer switch for the renin-angiotensin system.
AB  - The aspartyl protease renin was first isolated from the kidney by Tigerstedt more
      than a century ago. In the kidney, renin secretion is tightly linked to sodium
      intake and renal perfusion pressure, reflecting the important role of the renin
      angiotensin system (RAS) in controlling body fluid volume and blood pressure. The
      study by Mackins et al. in this issue of the JCI describes a novel source of
      renin: the mast cell (see the related article beginning on page 1063). This
      discovery suggests a distinct pathway for activation of the RAS that may have a
      particular impact on the pathogenesis of chronic tissue injury as well as more
      acute pathology such as arrhythmias in the heart.

PMID- 16585957
TI  - Pathomechanisms in rheumatoid arthritis--time for a string theory?
AB  - RA is a quintessential autoimmune disease with a growing number of cells,
      mediators, and pathways implicated in this tissue-injurious inflammation. Now
      Kuhn and colleagues have provided convincing evidence that autoantibodies
      reacting with citrullinated proteins, known for their sensitivity and specificity
      as biomarkers in RA, enhance tissue damage in collagen-induced arthritis (see the
      related article beginning on page 961). This study adds yet another soldier to
      the growing army of autoaggressive mechanisms that underlie RA. With great
      success researchers have dismantled the pathogenic subunits of RA, adding gene to
      gene, molecule to molecule, and pathway to pathway in an ever more complex scheme
      of dysfunction. The complexity of the emerging disease model leaves us
      speechless. It seems that with this wealth of data available, we need to develop
      a new theory for this disease. We may want to seek guidance from our colleagues
      in physics and mathematics who have successfully integrated their knowledge of
      elementary particles and the complexity of their interacting forces by
      formulating the string theory.

PMID- 16585958
TI  - Ontogeny of adrenal steroid biosynthesis: why girls will be girls.
AB  - Male and female external genitalia appear identical early in gestation.
      Testosterone exposure at 8-12 weeks' gestation causes male differentiation.
      Female fetuses virilize if their adrenals secrete excessive levels of androgens,
      as occurs in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
      This can be ameliorated by administering dexamethasone to the mother. A study by
      Goto et al. in this issue of the JCI provides a rationale for this treatment by
      demonstrating that the fetal hypothalamic-pituitary-adrenal axis is fully
      functional when the genitalia differentiate (see the related article beginning on
      page 953). Dexamethasone suppresses this axis, reducing abnormal secretion of
      adrenal androgens. Their results also show that cortisol synthesis by the fetal
      adrenal decreases after this period, allowing the adrenal to secrete high levels
      of dehydroepiandrosterone, an androgen precursor. However, this does not virilize
      female fetuses because androgens are aromatized to estrogens in the placenta.
      Thus normal sexual differentiation requires exquisite timing of fetal cortisol
      and androgen secretion versus placental capacity for aromatization.

PMID- 16585959
TI  - Cardiac 7-transmembrane-spanning domain receptor portfolios: diversify,
      diversify, diversify.
AB  - Enhanced signaling in myocytes by the G protein Gq has been implicated in cardiac
      hypertrophy and the transition to heart failure. alpha1-Adrenergic receptors
      (alpha1-ARs) are members of the 7-transmembrane-spanning domain (7-TM) receptor
      family and signal via interaction with Gq in the heart. The specific effects of a
      loss of alpha1-AR signaling in the heart are explored by O'Connell et al. in this
      issue of the JCI (see the related article beginning on page 1005). Paradoxically,
      gene ablation of the alpha 1A and alpha 1B subtypes in mice results in a
      maladaptive form of reactive cardiac hypertrophy from pressure overload, with a
      predisposition to heart failure. Thus signaling to the alpha1-AR (compared with
      signaling from other receptors such as angiotensin receptors, which also couple
      to Gq) appears to be specifically required for a normal hypertrophic response.
      This represents another example of how receptors that share common G proteins
      have diversified, developing unique signaling programs. These findings may have
      particular clinical relevance because of the widespread use of alpha1-AR
      antagonists in the treatment of hypertension and symptomatic prostate
      enlargement.

PMID- 16585960
TI  - Neotendon formation induced by manipulation of the Smad8 signalling pathway in
      mesenchymal stem cells.
AB  - Tissue regeneration requires the recruitment of adult stem cells and their
      differentiation into mature committed cells. In this study we describe what we
      believe to be a novel approach for tendon regeneration based on a specific
      signalling molecule, Smad8, which mediates the differentiation of mesenchymal
      stem cells (MSCs) into tendon-like cells. A biologically active Smad8 variant was
      transfected into an MSC line that coexpressed the osteogenic gene bone
      morphogenetic protein 2 (BMP2). The engineered cells demonstrated the
      morphological characteristics and gene expression profile of tendon cells both in
      vitro and in vivo. In addition, following implantation in an Achilles tendon
      partial defect, the engineered cells were capable of inducing tendon regeneration
      demonstrated by double quantum filtered MRI. The results indicate what we believe
      to be a novel mechanism in which Smad8 inhibits the osteogenic pathway in MSCs
      known to be induced by BMP2 while promoting tendon differentiation. These
      findings may have considerable importance for the therapeutic replacement of
      tendons or ligaments and for engineering other tissues in which BMP plays a
      pivotal developmental role.

PMID- 16585961
TI  - In humans, early cortisol biosynthesis provides a mechanism to safeguard female
      sexual development.
AB  - In humans, sexual differentiation of the external genitalia is established at 7
      12 weeks post conception (wpc). During this period, maintaining the appropriate
      intrauterine hormone environment is critical. In contrast to other species, this
      regulation extends to the human fetal adrenal cortex, as evidenced by the
      virilization that is associated with various forms of congenital adrenal
      hyperplasia. The mechanism underlying these clinical findings has remained
      elusive. Here we show that the human fetal adrenal cortex synthesized cortisol
      much earlier than previously documented, an effect associated with transient
      expression of the orphan nuclear receptor nerve growth factor IB-like (NGFI-B)
      and its regulatory target, the steroidogenic enzyme type 2 3beta-hydroxysteroid
      dehydrogenase (HSD3B2). This cortisol biosynthesis was maximal at 8-9 wpc under
      the regulation of ACTH. Negative feedback was apparent at the anterior pituitary
      corticotrophs. ACTH also stimulated the adrenal gland to secrete androstenedione
      and testosterone. In concert, these data promote a distinctive mechanism for
      normal human development whereby cortisol production, determined by transient
      NGFI-B and HSD3B2 expression, provides feedback at the anterior pituitary to
      modulate androgen biosynthesis and safeguard normal female sexual
      differentiation.

PMID- 16585962
TI  - Antibodies against citrullinated proteins enhance tissue injury in experimental
      autoimmune arthritis.
AB  - Antibodies against citrullinated proteins are specific and predictive markers for
      rheumatoid arthritis although the pathologic relevance of these antibodies
      remains unclear. To investigate the significance of these autoantibodies,
      collagen-induced arthritis (CIA) in mice was used to establish an animal model of
      antibody reactivity to citrullinated proteins. DBA/1J mice were immunized with
      bovine type II collagen (CII) at days 0 and 21, and serum was collected every 7
      days for analysis. Antibodies against both CII and cyclic citrullinated peptide,
      one such citrullinated antigen, appeared early after immunization, before joint
      swelling was observed. Further, these antibodies demonstrated specific binding to
      citrullinated filaggrin in rat esophagus by indirect immunofluorescence and
      citrullinated fibrinogen by Western blot. To evaluate the role of immune
      responses to citrullinated proteins in CIA, mice were tolerized with a citrulline
      containing peptide, followed by antigen challenge with CII. Tolerized mice
      demonstrated significantly reduced disease severity and incidence compared with
      controls. We also identified novel murine monoclonal antibodies specific to
      citrullinated fibrinogen that enhanced arthritis when coadministered with a
      submaximal dose of anti-CII antibodies and bound targets within the inflamed
      synovium of mice with CIA. These results demonstrate that antibodies against
      citrullinated proteins are centrally involved in the pathogenesis of autoimmune
      arthritis.

PMID- 16585964
TI  - Nrf2 is a critical regulator of the innate immune response and survival during
      experimental sepsis.
AB  - Host genetic factors that regulate innate immunity determine susceptibility to
      sepsis. Disruption of nuclear factor-erythroid 2-related factor 2 (Nrf2), a basic
      leucine zipper transcription factor that regulates redox balance and stress
      response, dramatically increased the mortality of mice in response to endotoxin-
      and cecal ligation and puncture-induced septic shock. LPS as well as TNF-alpha
      stimulus resulted in greater lung inflammation in Nrf2-deficient mice. Temporal
      analysis of pulmonary global gene expression after LPS challenge revealed
      augmented expression of large numbers of proinflammatory genes associated with
      the innate immune response at as early as 30 minutes in lungs of Nrf2-deficient
      mice, indicating severe immune dysregulation. The expression profile indicated
      that Nrf2 has a global influence on both MyD88-dependent and -independent
      signaling. Nrf2-deficient mouse embryonic fibroblasts showed greater activation
      of NF-kappaB and interferon regulatory factor 3 in response to LPS and
      polyinosinic-polycytidylic acid [poly(I:C)] stimulus, corroborating the effect of
      Nrf2 on MyD88-dependent and -independent signaling. Nrf2's regulation of cellular
      glutathione and other antioxidants is critical for optimal NF-kappaB activation
      in response to LPS and TNF-alpha. Our study reveals Nrf2 as a novel modifier gene
      of sepsis that determines survival by mounting an appropriate innate immune
      response.

PMID- 16585963
TI  - HTLV-1 propels untransformed CD4 lymphocytes into the cell cycle while protecting
      CD8 cells from death.
AB  - Human T cell leukemia virus type 1 (HTLV-1) infects both CD4+ and CD8+
      lymphocytes, yet it induces adult T cell leukemia/lymphoma (ATLL) that is
      regularly of the CD4+ phenotype. Here we show that in vivo infected CD4+ and CD8+
      T cells displayed similar patterns of clonal expansion in carriers without
      malignancy. Cloned infected cells from individuals without malignancy had a
      dramatic increase in spontaneous proliferation, which predominated in CD8+
      lymphocytes and depended on the amount of tax mRNA. In fact, the clonal expansion
      of HTLV-1-positive CD8+ and CD4+ lymphocytes relied on 2 distinct mechanisms-
      infection prevented cell death in the former while recruiting the latter into the
      cell cycle. Cell cycling, but not apoptosis, depended on the level of viral
      encoded tax expression. Infected tax-expressing CD4+ lymphocytes accumulated
      cellular defects characteristic of genetic instability. Therefore, HTLV-1
      infection establishes a preleukemic phenotype that is restricted to CD4+ infected
      clones.

PMID- 16585968
TI  - The first homoleptic bis(trifluoromethanesulfonyl)amide complex compounds of
      trivalent f-elements.
AB  - The synthesis and crystal structures of the first true homoleptic
      bis(trifluoromethanesulfonyl)amide complex compounds of trivalent f-elements are
      reported with [bmpyr]2[Ln(Tf2N)5], Ln = Nd, Tb and [bmpyr][Ln(Tf2N)4], Ln = Tm,
      Lu.

PMID- 16585967
TI  - Metallabenzenes and metallabenzenoids.
AB  - Metallabenzenes are analogues of benzene in which one of the benzene CH groups
      has been formally replaced by a transition metal and its ancillary ligands. This
      article summarises some of the important recent highlights of metallabenzene
      chemistry including the synthesis of the first platinabenzene, the synthesis of
      the first metallanaphthalene (an iridanaphthalene) and the development of new
      synthetic routes to metallabenzenes. The results of a number of theoretical
      studies that provide important insights into the nature and reactivity of
      metallabenzenes are discussed and in the concluding section some of the immediate
      goals and challenges in this field are identified.

PMID- 16585969
TI  - Crystal structure and thermochemical reactivity of an unusual copper complex that
      contains copper in four different coordination geometries.
AB  - According to X-ray single-crystal structure analysis,
      {[Cu(II)(en)2]2[Cu(I)2(CN)6]}[Cu(II)(en)2]2[Cu(I)(CN)3]2.2H2O contains copper in
      four different coordination environments: trigonal planar, square planar, square
      pyramidal and tetrahedral. The different coordination geometries of copper were
      investigated by quantum chemical calculations of model compounds, thus allowing
      to tentatively assign the different CN-bands in the IR spectrum. The thermolysis
      led to sub-microm sized rod-like copper(II) oxide particles.

PMID- 16585965
TI  - Alpha1-adrenergic receptors prevent a maladaptive cardiac response to pressure
      overload.
AB  - An alpha1-adrenergic receptor (alpha1-AR) antagonist increased heart failure in
      the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT), but it is unknown whether this adverse result was due to alpha1-AR
      inhibition or a nonspecific drug effect. We studied cardiac pressure overload in
      mice with double KO of the 2 main alpha1-AR subtypes in the heart, alpha 1A
      (Adra1a) and alpha 1B (Adra1b). At 2 weeks after transverse aortic constriction
      (TAC), KO mouse survival was only 60% of WT, and surviving KO mice had lower
      ejection fractions and larger end-diastolic volumes than WT mice.
      Mechanistically, final heart weight and myocyte cross-sectional area were the
      same after TAC in KO and WT mice. However, KO hearts after TAC had increased
      interstitial fibrosis, increased apoptosis, and failed induction of the fetal
      hypertrophic genes. Before TAC, isolated KO myocytes were more susceptible to
      apoptosis after oxidative and beta-AR stimulation, and beta-ARs were
      desensitized. Thus, alpha1-AR deletion worsens dilated cardiomyopathy after
      pressure overload, by multiple mechanisms, indicating that alpha1-signaling is
      required for cardiac adaptation. These results suggest that the adverse cardiac
      effects of alpha1-antagonists in clinical trials are due to loss of alpha1
      signaling in myocytes, emphasizing concern about clinical use of alpha1
      antagonists, and point to a revised perspective on sympathetic activation in
      heart failure.

PMID- 16585966
TI  - Cardiac mast cell-derived renin promotes local angiotensin formation,
      norepinephrine release, and arrhythmias in ischemia/reperfusion.
AB  - Having identified renin in cardiac mast cells, we assessed whether its release
      leads to cardiac dysfunction. In Langendorff-perfused guinea pig hearts, mast
      cell degranulation with compound 48/80 released Ang I-forming activity. This
      activity was blocked by the selective renin inhibitor BILA2157, indicating that
      renin was responsible for Ang I formation. Local generation of cardiac Ang II
      from mast cell-derived renin also elicited norepinephrine release from isolated
      sympathetic nerve terminals. This action was mediated by Ang II-type 1 (AT1)
      receptors. In 2 models of ischemia/reperfusion using Langendorff-perfused guinea
      pig and mouse hearts, a significant coronary spillover of renin and
      norepinephrine was observed. In both models, this was accompanied by ventricular
      fibrillation. Mast cell stabilization with cromolyn or lodoxamide markedly
      reduced active renin overflow and attenuated both norepinephrine release and
      arrhythmias. Similar cardioprotection was observed in guinea pig hearts treated
      with BILA2157 or the AT1 receptor antagonist EXP3174. Renin overflow and
      arrhythmias in ischemia/reperfusion were much less prominent in hearts of mast
      cell-deficient mice than in control hearts. Thus, mast cell-derived renin is
      pivotal for activating a cardiac renin-angiotensin system leading to excessive
      norepinephrine release in ischemia/reperfusion. Mast cell-derived renin may be a
      useful therapeutic target for hyperadrenergic dysfunctions, such as arrhythmias,
      sudden cardiac death, myocardial ischemia, and congestive heart failure.

PMID- 16585970
TI  - Dimetallo[3.3]para- and metacyclophanes by self-assembly of pyridylmethyl armed
      monoazatrithia- and monoazadithiaoxa-12-crown-4 ethers with Ag+ ions.
AB  - New pyridylmethyl armed-monoazadithiaoxa- and monoazatrithia-12-crown-4 have been
      prepared. The structures of the Ag+ complexes of the new ligands were
      investigated by X-ray crystallography, 1H NMR titrations, and FAB-MS
      measurements. In all cases, the Ag+ complexes form dimetallo[3.3]para- or
      metacyclophane structures depending on the position of the N atom of the pyridine
      rings.

PMID- 16585971
TI  - Dioxomolybdenum(VI) complexes as catalysts for the hydrosilylation of aldehydes
      and ketones.
AB  - The dioxomolybdenum(VI) complexes [MoO2Cl2] (1), [MoO2(acac)2] (2),
      [MoO2(S2CNEt2)2] (3), [CpMoO2Cl] (4), [MoO2(mes)2] (5) and the polymeric
      organotin-oxomolybdates [(R3Sn)2MoO4] [R = n-Bu (6), t-Bu (7), Me (8)] were
      examined as catalysts for the hydrosilylation of aldehydes and ketones with
      dimethylphenylsilane. Of these, [MoO2Cl2] (1) was the most efficient catalyst,
      affording quantitative yields of the corresponding silylated ethers at room
      temperature in acetonitrile. Complexes 2, 4-8 also catalyzed the same reaction
      but required heating at 80 degrees C and longer reaction times compared with 1.
      Compound 3 is inactive. The wide scope of molybdenum oxide-mediated
      hydrosilylation was established with a variety of aldehydes and ketones. Counter
      intuitively, the activity of is 1 highest in NCMe. In the absence of a carbonyl
      substrate, [MoO2Cl2(NCBu(t))] (10) reacts with HSiMe2Ph affording
      [MoO(OSiMe2Ph)Cl2]2 (11) which has been fully characterized by NMR and IR
      spectroscopy, elemental analyses and mass spectrometry. Addition of radical
      scavengers strongly slows down the [MoO2Cl2]-based hydrosilylation suggesting the
      intermediacy of oxygen-centered radicals.

PMID- 16585973
TI  - Chemical speciation in concentrated alkaline aluminate solutions in sodium,
      potassium and caesium media. Interpretation of the unusual variations of the
      observed hydroxide activity.
AB  - A detailed electrochemical investigation using H2/Pt electrode potentiometry as
      well as Raman and NMR spectroscopy was carried out to develop a comprehensive
      chemical explanation for the unusual patterns of hydroxide concentrations
      observed in strongly alkaline, highly concentrated aluminate solutions (Bayer
      liquors). For this, aluminate solutions with various alkaline metal background
      cations were investigated. The effect of the temperature on the observed patterns
      was also studied, and for comparison with solutions of similar concentrations,
      the chemical speciation of borate solutions was also studied. The formation of
      the NaOH 0 ion-pair has been proven with the formation constant (defined in terms
      of activities) beta 0 = 0.78 +/- 0.08. The formation of analogous KOH 0 or CsOH 0
      ion-pairs under the experimental conditions applied is negligible. Assuming the
      formation of the NaAl(OH)4 (0) ion-pair is not necessary for modeling the
      experimental findings, as its formation causes only secondary effects on the
      potentiometric patterns. It has also been shown that all experimental data can be
      interpreted quantitatively if the formation of the doubly charged dimeric
      aluminate species is included in the calculation of the changes in the mean
      activity coefficients. The formation constant of the aluminate dimer could not be
      estimated purely from the H2/Pt potentiometric data but a lower limit for its
      formation constant (defined in terms of activities) has been derived. These
      conclusions are in full congruency with those derived from the Raman spectra of
      solutions with similar concentrations, so the two independent experimental
      methods lead to the same set of chemical species in highly concentrated alkaline
      aluminate solutions.

PMID- 16585972
TI  - Insights into the making of a stable silylene.
AB  - Reduction of Cl2Si[(NR)2C6H4-1,2] (R = CH2Bu(t)) with potassium is known to lead
      to the stable silylene Si[(NR)2C6H4-1,2] (1). However, silylene is now shown to
      react further with an alkali metal (Na or K) to yield the (1)(2)2-, c-(1)(3)-*, c
      (1)(3)2- or c-(1)(4)2- derivatives. Reduction of Cl2Si[(NR)2C6H4-1,2] (R = CH2CH3
      or CH2CHMe2) with potassium does not lead to an isolable silylene, but such a
      silylene is proposed to be an intermediate and, as for 1, reacts further to
      afford the potassium salts of c-[Si{(NR)2C6H4-1,2}]4-* and c-[Si{(NR)2C6H4
      1,2}](4)2-. The pathways leading to the anionic cyclotri- and cyclotetrasilanes
      are discussed and supported experimentally; including by X-ray structures of
      relevant intermediates.

PMID- 16585974
TI  - A computational study of oxidation of ruthenium porphyrins via ORu(IV) and
      ORu(VI)O species.
AB  - An unrestricted density functional theory (UDFT) was applied to study the
      oxidation of ruthenium porphyrins, [RuP], via an interaction with molecular
      oxygen. The important role of dimeric [RuP] complexes, i.e. [RuP]-O2-[RuP], in
      the oxidation mechanism and particular in the cleavage of O-O bond of molecular
      oxygen has been studied. Geometries and relative Gibbs free energies of the
      intermediate Ru-complexes, i.e. dimeric oxo-Ru-porphyrins and O2Ru(II)-(or O2-
      Ru(III))-, ORu(IV)- and ORu(VI)O-porphyrins, were evaluated along the proposed
      reaction pathway. The detailed thermodynamic data of the oxidation reaction
      [Ru(II)P] --> O[Ru(IV)P] --> O[Ru(VI)P]O and important aspects of the vibrational
      spectra of an oxo-[RuP] has been presented.

PMID- 16585976
TI  - Theoretical investigation of paramagnetic group 13 diazabutadiene radicals:
      insights into the prediction and interpretation of EPR spectroscopy parameters.
AB  - The electronic structures and the spin density distributions of the group 13 1,4
      diaza(1,3)butadiene (DAB) radicals [(R-DAB)2M]*, [(R-DAB)MX2] and {[(R
      DAB)MX]2}** (M = Al, Ga, In; X = F, Cl, Br, I; R = H, Me, tBu, Ph) are studied
      using density functional theory at both non-relativistic and relativistic levels
      of theory. The calculations demonstrate that all systems share a qualitatively
      similar electronic structure and are primarily ligand centred pi-radicals. The
      calculated metal, nitrogen and hydrogen hyperfine couplings are found to be
      independent of the identity of the R-group and the halogen atom. They are,
      however, dependent on the geometry and oxidation state of the metal centre. Both
      observed trends contrast what has previously been deduced from the interpretation
      of experimental EPR and ENDOR spectra. Good agreement between the calculated and
      experimentally determined hyperfine coupling constants is found only for some of
      the studied systems. Instances where significant discrepancies between the
      calculated and experimental values exist can be attributed to the tendency of
      these systems toward complex solution behaviour, which results in differences
      between the solid state and solution structures of certain complexes. A careful
      re-evaluation of the experimental data as well as calculated reaction energies
      lends strong support to this hypothesis. However, further studies are needed
      before the identity of some of the studied radical species in solution can be
      unambiguously determined.

PMID- 16585975
TI  - 4-Methoxy- and 4-cyano-substituted lithium aryloxides: electronic effects of
      substituents on aggregation.
AB  - The para-substituted lithium aryloxides [{4-NC-C6H4OLi.(Pyr)2}2.Pyr] 1a, [{4-NC
      C6H4OLi.(THF)2}2] 1b, [{4-MeO-C6H4OLi.Pyr}4] 2a, [4-MeO-C6H4OLi.(THF)n] 2b, [{4
      NC-2,6-(t-Bu)2-C6H2OLi.(Pyr)2}infinity] 3a, [{4-NC-2,6-(t-Bu)2
      C6H2OLi.(THF)2}infinity] 3b, [{4-MeO-2,6-(t-Bu)2-C6H2OLi.Pyr}2.(Pyr)2] 4a, and [4
      MeO-2,6-(t-Bu)2-C6H2OLi.(THF)n] 4b were prepared by the direct deprotonation of
      the corresponding phenol with an alkyllithium base (BuLi or MeLi) in the
      appropriate solvent, either pyridine or THF. All compounds were characterized by
      1H and 13C NMR spectroscopy, and the crystal structures of 1a, 1b, 2a, 3a, 3b and
      4a were elucidated. The cyano derivatives 1a and 1b adopt discrete tetrasolvated
      Li2O2 ring dimers whereas the methoxy analogue 2a crystallizes as a tetrasolvated
      molecular tetramer with a pseudo cubic Li4O4 core. The sterically encumbered
      cyano derivatives 3a and 3b form isostructural 1D polymeric chains of monomers
      via bridging of the phenolate ligands through Li...NC and Li-O contacts. In
      comparison, the crystal structure of the methoxy counterpart 4a is a disolvated
      molecular Li2O2 ring dimer. Solution NMR spectroscopic studies of 1-4 in d5
      pyridine and d8-THF indicate that the methoxy complexes are more highly
      aggregated than the cyano derivatives, consistent with the solid-state studies.
      Ab initio molecular orbital calculations at the HF/6-31G* level of theory
      indicate that the origin of the aggregation state variations between the cyano
      and methoxy complexes is due to electronic effects.

PMID- 16585977
TI  - Models of hypoxia activated prodrugs: Co(III) complexes of hydroxamic acids.
AB  - Co(III) complexes of simple hydroxamic acids have been evaluated as models of
      hypoxia activated prodrugs containing MMP inhibitors. The complexes are based
      upon a proposed carrier system comprising the tripodal tetradentate ligand tris(2
      methylpyridyl)amine (tpa) with the hydroxamate functionality occupying the
      remaining coordination sites of the Co centre. Acetohydroxamato (aha),
      propionhydroxamato (pha), and benzohydroxamato (bha) complexes were synthesised
      and characterised by single crystal X-ray diffraction. For aha and pha both the
      hydroxamato and hydroximato (deprotonated) forms were obtained and were readily
      interconverted by pH manipulation; for bha only the hydroximato complex was
      obtained as a stable species. Electrochemical analysis was used to probe the
      redox chemistry of the complexes and assess their ease of reduction. All of the
      complexes displayed irreversible reduction and had low cathodic peak potentials.
      This suggests that the Co-tpa carrier system would provide a suitably inert
      framework to deliver the drugs to target sites intact yet would release the
      ligands upon reduction to the more labile Co(II) oxidation state.

PMID- 16585978
TI  - Multinuclear copper complexes of pyridylmethylamide ligands.
AB  - Copper complexes of a family of pyridylmethylamide ligands HL(Ph), HL(Me3) and
      HL(Ph3) were synthesized and characterized [HL(Ph) = 2-phenyl-N-(2
      pyridylmethyl)acetamide; HL(Me3) = 2,2-dimethyl-N-(2-pyridylmethyl)propionamide;
      HL(Ph3) = 2,2,2-triphenyl-N-(2-pyridylmethyl)acetamide]. The reaction of
      copper(II) salts with the HL family and triethylamine in methanol yields
      copper(II) complexes [Cu4(L(Ph))4(OH)2](ClO4)2 (1),
      [Cu2(HL(Me3))2(OMe)2(MeOH)2](OTf)2 (2) and [Cu2(HL(Ph3))2(OMe)2(MeOH)2](OTf)2
      (3). The complexes have different nuclearity owing to varying steric properties
      of the ligands used. Complex 1 self-assembles in the presence of excess base to
      form a tetranuclear complex. Complexes 2 and 3 are binuclear and are bridged by a
      pair of methoxide ligands. Steric encumbrance of the ligands in 2 and 3 prevent
      cluster formation.

PMID- 16585979
TI  - Organometallic chemistry on periodic mesoporous organosilicas: generation of
      surface-confined zinc and yttrium centres.
AB  - Periodic mesoporous ethylenesilicas with hexagonal P6mm and cubic Fm3m/Pm3n
      symmetry were prepared by using divalent surfactant C(16-3-1) and binary
      surfactant mixtures C(18-3-1) and C18TABr as structure-directing agents,
      respectively, under basic conditions. A tetramethyldisilazane-based surface
      silylation was carried out under mild conditions affording hybrid materials
      SiHMe2@PMO[MCM-41], SiHMe2@PMO[KIT-5] and SiHMe2@PMO[SBA-1], corresponding to
      silanol group populations of ca. 1.46, 0.67 and 1.63 mmol g(-1), respectively.
      New molecular zinc precursor compounds Zn[N(SiHMe2)2]2 and EtZn(OSiHtBu2) were
      synthesized via salt metathesis and alkane elimination procedures from ZnCl2 and
      LiN[SiH(CH3)2]2, HOSiHtBu2 and ZnEt2, respectively. Organozinc and organoyttrium
      complexes were reacted with the surface silanol groups according to a
      heterogeneously performed silylamide route, aswell as an alkane elimination
      reaction, yielding Zn[N(SiHMe2)2]@PMO[MCM-41], Zn[N(SiHMe2)2]@PMO[KIT-5],
      Zn[N(SiHMe2)2]@PMO[SBA-1], Zn[N(SiMe3)2]@PMO[MCM-41], Zn[N(SiMe3)2]@PMO[KIT-5],
      Zn[N(SiMe3)2]@PMO[SBA-1], Y[N(SiHMe2)2]x(THF)y@PMO[MCM-41],
      Y[N(SiHMe2)2]x(THF)y@PMO[KIT-5], Y[N(SiHMe2)2]x(THF)y@PMO[SBA-1] and
      Zn(OSiHtBu2)@PMO[MCM-41]. The metal loading mainly depended on the surface
      silanol group population, size and shape of metal-coordinated ligand, and
      reaction time as shown for Zn contents in the range of 4.2 to 10.6 wt%. In
      addition, a preferred N(SiHMe2)2/OC6H2tBu2-2,6-Me-4 ligand exchangeability was
      found for the large yttrium surface centres. The parent and functionalized
      materials were characterized by powder X-ray diffraction, elemental analysis, N2
      physisorption, FTIR, 13C CP and 1H MAS NMR spectroscopy.

PMID- 16585980
TI  - Phenotypic variation and allelic heterogeneity in young patients with Papillon
      Lefevre syndrome.
AB  - Papillon-Lefevre syndrome is an autosomal recessive disorder characterized by
      palmoplantar hyperkeratosis and aggressive periodontitis. The aim of the study
      was to identify underlying cathepsin C mutations in 39 subjects with Papillon
      Lefevre syndrome and to explore any phenotypic associations. Genotyping and
      mutation analyses were performed using standard molecular techniques, and
      dermatological and oral characteristics were assessed with a semiquantitative
      clinical score. Three genotypes were present at microsatellite marker D11S1780
      and two underlying mutations were identified. The most common genotype (183/183)
      was associated with an 815G --> C mutation in exon 6 resulting in an arginine to
      proline change at amino acid 272 (R272P). Patients with the 173/173 genotype
      revealed an exon 7 G300D mutation resulting in a glycine to aspartic acid change
      at amino acid 300. The mutation in a family with 189/189 genotype remained
      unknown. A significant difference in hyperkeratosis of the feet was found between
      the patients with mutations G300D and R272P ( p < 0.05), but not regarding hands
      or periodontal condition. Young girls displayed significantly less palmoplantar
      hyperkeratosis ( p < 0.05) than young boys. In conclusion, considerable
      phenotypic heterogeneity was observed within the two cardinal mutations and in
      the 189/189 genotype.

PMID- 16585981
TI  - Increased retest reactivity by both patch and use test with
      methyldibromoglutaronitrile in sensitized individuals.
AB  - Hyperreactivity on re-exposure of previous allergic contact dermatitis skin areas
      has been previously demonstrated. This study aimed to investigate in
      methyldibromoglutaronitrile (MDBGN) allergic patients whether skin with previous
      allergic dermatitis from MDBGN showed an augmented response on re-exposure by
      both a patch test challenge and a use test with a liquid soap preserved with
      MDBGN. MDBGN dermatitis was elicited on the back and arms of sensitized
      individuals. One month later the previously eczematous areas were challenged with
      MDBGN. On the back, the test sites were patch-tested with a serial dilution of
      MDBGN and a use test was performed on the arms with an MDBGN-containing soap. A
      statistically significant increased response was seen on the areas with previous
      dermatitis on the back. Eight of the nine patients who developed dermatitis on
      the arms from the MDBGN-containing soap had an augmented response on areas with
      prior allergic contact dermatitis. Even though the allergic dermatitis appeared
      to be healed, an increased reactivity to allergen re-exposure was demonstrated
      both by patch test and use test challenge.

PMID- 16585982
TI  - Prolonged topical application of tacrolimus inhibits immediate hypersensitivity
      reactions by reducing degranulation of mast cells.
AB  - We studied the effects of prolonged topical application of tacrolimus on
      immediate hypersensitivity reactions. Tacrolimus, betamethasone or petrolatum was
      applied to the footpad of mice for up to 28 days after immunization, and the foot
      swelling response to allergen was estimated. The reactions in tacrolimus-treated
      mice decreased significantly from day 14, while those in betamethasone-treated
      mice decreased significantly from day 7. Although the number of mast cells in the
      foot skin of each group did not differ significantly, the percentage of
      degranulated mast cells decreased in the tacrolimus-treated group on days 7 and
      14. The TUNEL method indicated that there were no apoptotic mast cells in the
      foot skin of tacrolimus-treated mice. Continuous application of topical
      tacrolimus ointment may suppress immediate hypersensitivity reactions by reducing
      the degranulation of mast cells, rather than by decreasing their number.

PMID- 16585983
TI  - Effect of psoriasis activity on metalloproteinase-1 and tissue inhibitor of
      metalloproteinase-1 in plasma and lesional scales.
AB  - The aim of this study was to evaluate the association between psoriasis severity
      and concentrations of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of
      metalloproteinase-1 (TIMP-1) in plasma and scales from psoriatic lesions,
      measured with an enzyme immunoassay in 24 patients and analysed with respect to
      psoriasis area and severity index (PASI). The mean plasma concentrations of both
      proteins in psoriatic patients significantly exceeded the control values. The
      proteins were also detectable in scales. There was a significant correlation
      between plasma MMP-1 concentration and the disease duration. The PASI values
      showed significant positive correlation with plasma TIMP-1 and significant
      negative correlation with MMP-1 content in scales. The highest plasma MMP-1
      concentration was observed in patients with mild forms whereas the highest plasma
      TIMP-1 concentrations were demonstrated in severe forms of psoriasis. Our results
      confirm the role of these proteins in pathogenesis of psoriasis. In severe forms,
      a decrease in both MMP-1 and TIMP-1 was observed in scales, suggesting their
      insufficient tissue expression, which can be a crucial element of psoriasis
      aggravation.

PMID- 16585984
TI  - Treatment of palmoplantar psoriasis with monochromatic excimer light (308-nm)
      versus cream PUVA.
AB  - Palmoplantar psoriasis is a chronic disease, which is very resistant to treatment
      and often leads to severe disabilities. Photochemotherapy employing psoralens
      combined with UVA irradiation (PUVA) is a well-accepted therapy for palmoplantar
      psoriasis. Its topical application (bath PUVA; cream PUVA) avoids the typical
      side effects of orally applied psoralens. We compared the efficacy of cream PUVA
      therapy with monochromatic excimer light therapy, a treatment modality employing
      308-nm UVB radiation generated by a new kind of light source. Ten patients with
      psoriasis of the palms and soles were randomly assigned to receive cream PUVA on
      one side and 308-nm UVB on the contralateral side. Based on the psoriasis area
      and severity index (PASI) score, clinical assessment was carried out before and 5
      weeks after the beginning of the study. At the end of the treatment period both
      test groups showed a remarkable PASI score reduction (308-nm UVB, 63.57%; cream
      PUVA, 64.64%). No relevant adverse effects were observed, except for mild
      irritation in a few patients. After a 12-week follow-up, a relapse of the disease
      was only observed in one patient. Thus, mono-chromatic excimer light cleared
      palmoplantar psoriasis as rapidly as cream PUVA. In contrast to cream PUVA,
      monochromatic excimer light therapy is not associated with prior drug
      application. This might lead to a lower incidence of adverse reactions and better
      compliance. Therefore, monochromatic excimer light therapy seems to be a useful
      new therapeutic option for palmoplantar psoriasis.

PMID- 16585985
TI  - Topical photodynamic therapy for prevention of new skin lesions in renal
      transplant recipients.
AB  - Preclinical data suggest that topical methyl aminolevulinate photodynamic therapy
      may have potential in preventing new skin lesions in transplant recipients. An
      open intra-patient randomized study investigated the prevention potential of this
      treatment in 27 renal transplant patients with actinic keratoses and other skin
      lesions in two circular contralateral areas (5 cm diameter). The treatment area
      surface was debrided and methyl aminolevulinate cream (160 mg/g) was applied for
      3 h prior to illumination by non-coherent red light (570-670 nm, light dose 75
      J/cm2). The control area was not treated. The mean time to occurrence of the
      first new lesion was significantly longer in treated than control areas (9.6 vs
      6.8 months, treatment difference 2.9 [95% confidence interval 0.2 to 5.5] months,
      p = 0.034). Over 12 months, 62% (16/26) of treated areas were free from new
      lesions compared with 35% (9/26) in control areas. These findings indicate that
      topical methyl aminolevulinate photodynamic therapy is a promising preventive
      treatment against new skin lesions in immunosuppressed patients.

PMID- 16585987
TI  - Pimecrolimus and narrowband UVB as monotherapy or combination therapy in children
      and adolescents with atopic dermatitis.
AB  - Topical pimecrolimus and narrowband ultraviolet B (UVB) are both known to be
      effective in treating atopic dermatitis. We compared the clinical efficacy of
      monotherapy with either twice daily topical 1% pimecrolimus cream or twice weekly
      narrowband UVB, and combination therapy in 26 children and adolescents with
      moderate to severe atopic dermatitis in a half-side manner for 6 weeks. Twenty
      four patients completed the study. Monotherapy and combination therapy notably
      reduced the scores of the Eczema Area and Severity Index ( p = 0.002) and the
      severity of pruritus ( p < or = 0.004). There was no significant difference in
      therapeutic efficacy among the treatment regimens at week 6. In conclusion,
      because of the lack of short-term additive therapeutic efficacy, concomitant use
      of pimecrolimus and narrowband UVB is inadvisable in treating moderate to severe
      atopic dermatitis in children and adolescents.

PMID- 16585986
TI  - 0.3% Tacrolimus gel and 0.5% Tacrolimus cream show efficacy in mild to moderate
      plaque psoriasis: Results of a randomized, open-label, observer-blinded study.
AB  - The efficacy and safety of 0.3% tacrolimus gel and 0.5% tacrolimus cream compared
      with calcipotriol ointment were evaluated in adults (n = 124) with mild to
      moderate plaque psoriasis. Treatment was twice daily for a maximum of 12 weeks.
      Clinical efficacy was assessed by the percentage change in the local psoriasis
      severity index of a target lesion between baseline and week 12. By week 12, the
      median percentage changes in local psoriasis severity index of the target lesions
      in the tacrolimus gel, tacrolimus cream and calcipotriol groups were 55.6%, 50.0%
      and 58.6%, respectively (no statistically significant differences). Clinical
      improvement was observed after one week and increased throughout the study.
      Tacrolimus-treated patients experienced more application site skin burning
      (tacrolimus gel and cream both 31.0% versus 7.5% for calcipotriol; p = 0.011).
      Skin burning was mostly mild in intensity and decreased substantially after 1
      week of treatment. There were no differences in the nature and incidence of
      infections and no clinically relevant changes in laboratory values.

PMID- 16585988
TI  - Clinical spectrum of cutaneous Langerhans' cell histiocytosis mimicking various
      diseases.
AB  - Langerhans' cell histiocytosis summarizes a spectrum of diseases on the basis of
      histogenetic criteria. These are characterized by an accumulation of cells with
      Langerhans' cell phenotype in one or multiple organs. Up to 50% of patients with
      either single or multi-organ manifestation of Langerhans' cell histiocytosis
      initially present with cutaneous symptoms. Nevertheless, cutaneous Langerhans'
      cell histiocytosis is rare and heterogeneous in its clinical features and
      therefore prone to misdiagnosis. We report on five patients, two infants and
      three adults, suffering from cutaneous Langerhans' cell histiocytosis, either
      singly or as part of multi-organ disease. The different skin features
      morphologically mimicking other entities are shown and the differential diagnoses
      are discussed. The correct diagnosis in all presented cases is based on
      immunohistological examination, showing a histiocytic infiltrate positively
      staining with anti-S100 antibodies, CD1a and--apart from one case--with CD207
      (langerin).

PMID- 16585989
TI  - Metastasis of a malignant melanoma 2 years after carbon dioxide laser treatment
      of a pigmented lesion: case report and review of the literature.
AB  - A 64-year-old woman with a clinically diagnosed 'lentigo simplex' on her right
      cheek was dermatologically treated several times with a CO2 laser. Three years
      later she showed a metastasis of a malignant melanoma in her right parotid gland.
      Considering this case, as well as other published cases reporting malignant
      melanomas occurring after laser treatment, we again underscore that
      naevomelanocytic lesions are not a routine indication for laser treatment.

PMID- 16585990
TI  - Clinicopathological analysis of 1571 cutaneous malignant melanomas in Valencia,
      Spain: factors related to tumour thickness.
AB  - Epidemiological studies on cutaneous melanoma in Mediterranean countries are
      scarce. Our aim was to perform a descriptive analysis of melanoma cases diagnosed
      in Valencia, Spain, and to evaluate the relationship between Breslow thickness
      and some clinical features. A total of 1571 patients with histologically
      confirmed cutaneous malignant melanoma diagnosed at the two main referral
      melanoma centres were evaluated retrospectively. For each patient the following
      clinical and pathological characteristics were selected: age, gender, anatomic
      site, histogenetic type, Breslow thickness, presence of ulceration, the stage,
      and symptoms such as bleeding, changes in size and colour, altered sensations and
      previous traumas. Chi-squared tests were performed together with logistic
      regression to evaluate the relationship of variables with tumour thickness.
      Tumour thickness was independently correlated with increasing age, presence of
      bleeding, location on hand or foot, and presence of altered sensations. Female
      sex and presence of a change in colour were associated with thin melanomas.
      Ideally, public awareness campaigns concerning the risks that exist should be
      aimed at subgroups such as men and people of an advanced age who generally
      present with thicker tumours. Emphasis should be placed on irregularities or
      changes in pigmentation, as these appear to be the first indicators of the
      development of a melanoma.

PMID- 16585991
TI  - Dovobet ointment under occlusion overnight for troublesome scalp psoriasis.

PMID- 16585992
TI  - Darier's disease associated with cutis verticis gyrata, hyperprolactinaemia and
      depressive disorder.

PMID- 16585993
TI  - Cyclin A expression in chronic leg ulcers.

PMID- 16585994
TI  - Tumoral macroglobulinosis of the skin: In situ release of IgM.

PMID- 16585995
TI  - Systemic absorption of topical tacrolimus in Pyoderma gangrenosum.

PMID- 16585996
TI  - An incomplete circle of alopecia: a new case of halo scalp ring?

PMID- 16585998
TI  - Pimecrolimus cream 1% is effective in seborrhoeic dermatitis refractory to
      treatment with topical corticosteroids.

PMID- 16585997
TI  - Churg-Strauss syndrome with cutaneous and neurological manifestations preceding
      asthma.

PMID- 16585999
TI  - Pimecrolimus cream 1% is effective in a case of granulomatous rosacea.

PMID- 16586000
TI  - Postherpetic paresis mimicking an abdominal herniation.

PMID- 16586001
TI  - Bullous lesions in chronic lymphocytic leukaemia: pemphigoid or insect bites?

PMID- 16586002
TI  - Point mutation in the STS gene in a severely affected patient with X-linked
      recessive ichthyosis.

PMID- 16586003
TI  - Neurofibromatosis 1/Noonan syndrome associated with Hashimoto's thyroiditis and
      vitiligo.

PMID- 16586004
TI  - Digital arteriovenous malformation.

PMID- 16586005
TI  - Successful treatment of Pyoderma gangrenosum with potassium iodide.

PMID- 16586006
TI  - Giant dermatofibroma appearing during pregnancy.

PMID- 16586007
TI  - Long-lasting remission of pemphigus vulgaris treated with rituximab.

PMID- 16586008
TI  - Strawberry gingivitis: an isolated manifestation of Wegener's granulomatosis?

PMID- 16586009
TI  - Naevus lipomatosus cutaneous superficialis of Hoffmann-Zurhelle with
      angiokeratoma of Fordyce.

PMID- 16586011
TI  - A multi-center phase II study of BMS-247550 (Ixabepilone) by two schedules in
      patients with metastatic gastric adenocarcinoma previously treated with a taxane.
AB  - PURPOSE: Ixabepilone is one of the epothilones, a new class of cytotoxics, that
      function as microtubule-stabilizing agents. With the primary endpoint of
      assessing ixabepilone's response rate against metastatic gastric cancer
      previously treated with a taxane, we performed a multi-center phase II trial.
      PATIENTS AND METHODS: Patients with histologically documented metastatic gastric
      or gastroesophageal adenocarcinoma, who had previously received a taxane, were
      eligible. Patients were required to have near normal organ function, > or =18
      years of age, ECOG performance status of 0 or 1. A written informed consent was
      obtained from all patients. Ixabepilone was administered over one hour
      intravenously at a dose of 50 mg/m2 every 21 days (23 patients; cohort A) and 24
      subsequent patients were treated with an amended protocol schedule to receive 6
      mg/m2 intravenously on days 1-5 every 21 days (cohort B). RESULTS: A total of 47
      patients were treated. Most patients were men with a median performance status of
      1. Two of 23 patients in cohort A achieved a confirmed partial response (9%, 95%
      CI 1.1-28%) but none of the 24 patients in cohort B achieved a response. A higher
      proportion of patients in cohort A experienced Grade 3/4 toxicities compared with
      those in cohort B. CONCLUSIONS: Ixabepilone, on a once every 21-day schedule, is
      modestly active against metastatic gastric cancer previously treated with a
      taxane. The days 1-5 every 21 days schedule had a more favorable safety profile
      but no activity. The results of this study suggest that once every 21-day
      ixabepilone schedule should be pursued further in untreated gastric or
      gastroesophageal adenocarcinoma patients.

PMID- 16586012
TI  - Studies on reaction of amino acids and triplet thioxanthone derivatives by laser
      flash photolysis.
AB  - Excitation of the thioxanthone derivatives (TXs), 2, 4-diethylthioxanthone (DETX)
      and 2-(2,3-epoxypropyloxy) thioxanthone (ETX) in acetonitrile/water mixture
      solution (1:1, v/v) upon 355 nm laser flash produced the triplet of TXs
      ((3)TXs(*)). Characteristic absorption spectra of (3)TXs(*)(590 nm) were recorded
      and rate constants of (3)TXs(*) quenched by O(2) and by its ground state were
      determined (9.8 x 10(9) M(-1) s(-1), 7.3 x 10(9) M(-1) s(-1) and 2.6 x 10(8) M(
      1) s(-1), 2.2 x 10(8) M(-1) s(-1) respectively). The reactions of some amino
      acids oxidized by (3)TXs(*) were carried out. It has been found that tryptophan
      (Trp) and tyrosine (Tyr) can quench (3)TXs(*) via electron transfer process and
      related quenching rate constants were obtained. (3)TXs(*) induced protein damage
      was investigated using electrophoresis and significant levels of dimerisation
      were observed under aerobic and anaerobic conditions. The influence of photo
      sensitizer's structure on photo-oxidation of amino acid and protein has been
      discussed.

PMID- 16586014
TI  - DNA electrophoresis in designed channels.
AB  - We present a simple description on the electrophoretic dynamics of
      polyelectrolytes going through designed channels with narrow constrictions of
      slit geometry. By analyzing rheological behaviours of the stuck chain, which is
      coupled to the effect of solvent flow, three critical electric fields (permeation
      field E((per)) approximately N(-1), deformation field E((def)) approximately N(
      3/5) and injection field E((inj)) approximately N(0), with N polymerization
      index) are clarified. Between E((per)) and E((inj)), the chain migration is
      dictated by the driven activation process. In particular, at E > E((def)), the
      stuck chain at the slit entrance is strongly deformed, which enhances the rate of
      the permeation. From these observations, electrophoretic mobility at a given
      electric field is deduced, which shows non-monotonic dependence on N. For long
      enough chains, mobility increases with N, in good agreement with experiments. An
      abrupt change in the electrophoretic flow at a threshold electric field is
      formally regarded as a nonequilibrium phase transition.

PMID- 16586015
TI  - The role of the amorphous fraction for the equilibrium shape of polymer single
      crystals.
AB  - The equilibrium state of polymer single crystals is considered by explicitly
      taking into account the amorphous fraction formed by loops and tails of the
      chains using a statistical model introduced by Muthukumar (Philos. Trans. R. Soc.
      London, Ser. A 361, 539 (2003)). We show that under realistic conditions below
      the equilibrium melting temperature, tight loops and close re-entries are
      favored, and that the amorphous fraction can be mapped into an excess surface
      free energy. The model is extended to many-chain crystals where it is shown that
      the lamellar thickness increases with the number of chains in the crystal and
      extended-chain conformations are thermodynamically favored if the number of
      chains in the crystal is sufficiently large. The number of chains necessary to
      form an extended-chain crystal in thermodynamic equilibrium scales with the
      square of the degree of polymerization of the chains. We discuss the temperature
      behavior of the equilibrium crystal thickness in the under-cooled state.

PMID- 16586016
TI  - Evidence for a diverse Cys-loop ligand-gated ion channel superfamily in early
      bilateria.
AB  - The genome sequences of Caenorhabditis elegans and Drosophila melanogaster reveal
      a diversity of cysteine-loop ligand-gated ion channels (Cys-loop LGICs) not found
      in vertebrates. To better understand the evolution of this gene superfamily, I
      compared all Cys-loop LGICs from rat, the primitive chordate Ciona intestinalis,
      Drosophila, and C. elegans. There are two clades of GABA receptor subunits that
      include both vertebrate and invertebrate orthologues. In addition, I identified
      nine clades of anion channel subunits found only in invertebrates, including
      three that are specific to C. elegans and two found only in Drosophila. One well
      defined clade of vertebrate cation channel subunits, the alpha 7 nicotinic
      acetylcholine receptor subunits (nAChR), includes invertebrate orthologues. There
      are two clades of invertebrate nAChRs, one of alpha-type subunits and one of non
      alpha subunits, that are most similar to the two clades of vertebrate neuronal
      and muscle alpha and non-alpha subunits. There is a large group of divergent C.
      elegans nAChR-like subunits partially resolved into clades but no orthologues of
      5HT3-type serotonin receptors in the invertebrates. The topology of the trees
      suggests that most of the invertebrate-specific Cys-loop LGIC clades were present
      in the common ancestor of chordates and ecdysozoa. Many of these disappeared from
      the chordates. Subsequently, selected subunit genes expanded to form large
      subfamilies.

PMID- 16586018
TI  - Induction of plant defense enzymes and phenolics by treatment with plant growth
      promoting rhizobacteria Serratia marcescens NBRI1213.
AB  - In greenhouse experiments, plant growth-promoting rhizobacteria (PGPR) Serratia
      marcescens NBRI1213 was evaluated for plant growth promotion and biologic control
      of foot and root rot of betelvine caused by Phytophthora nicotianae.
      Bacterization of betelvine (Piper betle L.) cuttings with S. marcescens NBRI1213
      induced phenylalanine ammonia-lyase, peroxidase, and polyphenoloxidase activities
      in leaf and root. Qualitative and quantitative estimation of phenolic compounds
      was done through high-performance liquid chromatography (HPLC) in leaf and root
      of betelvine after treatment with S. marcescens NBRI1213 and infection by P.
      nicotianae. Major phenolics detected were gallic, protocatechuic, chlorogenic,
      caffeic, ferulic, and ellagic acids by comparison of their retention time with
      standards through HPLC. In all of the treated plants, synthesis of phenolic
      compounds was enhanced compared with control. Maximum accumulation of phenolics
      was increased in S. marcescens NBRI1213-treated plants infected with P.
      nicotianae. In a greenhouse test, bacterization using S. marcescens NBRI1213
      decreased the number of diseased plants compared with nonbacterized controls.
      There were significant growth increases in shoot length, shoot dry weight, root
      length, and root dry weight, averaging 81%, 68%, 152%, and 290%, respectively,
      greater than untreated controls. This is the first report of PGPR-mediated
      induction of phenolics for biologic control and their probable role in protecting
      betelvine against P. nicotianae, an important soil-borne phytopathogenic fungus.

PMID- 16586017
TI  - Protein evolutionary rates correlate with expression independently of synonymous
      substitutions in Helicobacter pylori.
AB  - In free-living microorganisms, such as Escherichia coli and Saccharomyces
      cerevisiae, both synonymous and nonsynonymous substitution frequencies correlate
      with expression levels. Here, we have tested the hypothesis that the correlation
      between amino acid substitution rates and expression is a by-product of selection
      for codon bias and translational efficiency in highly expressed genes. To this
      end, we have examined the correlation between protein evolutionary rates and
      expression in the human gastric pathogen Helicobacter pylori, where the absence
      of selection on synonymous sites enables the two types of substitutions to be
      uncoupled. The results revealed a statistically significant negative correlation
      between expression levels and nonsynonymous substitutions in both H. pylori and
      E. coli. We also found that neighboring genes located on the same, but not on
      opposite strands, evolve at significantly more similar rates than random gene
      pairs, as expected by co-expression of genes located in the same operon. However,
      the two species differ in that synonymous substitutions show a strand-specific
      pattern in E. coli, whereas the weak similarity in synonymous substitutions for
      neighbors in H. pylori is independent of gene orientation. These results suggest
      a direct influence of expression levels on nonsynonymous substitution frequencies
      independent of codon bias and selective constraints on synonymous sites.

PMID- 16586019
TI  - Broken hyphae of the basidiomycete Crinipellis perniciosa allow quantitative
      assay of toxicity.
AB  - Breaking of hyphae derived from growth of the phytopathogenic fungus Crinipellis
      perniciosa in liquid media yielded cell aggregates that performed as "quasi
      single cell" in toxicity assays. When treated with the chemical mutagens 4
      nitroquinoleine-1-oxide (4NQO), hydrogen peroxide (H2O2), or paraquat (PAQ) as
      well as with ultraviolet light (UVC), broken hyphae of C. perniciosa gave a
      single cell-like response, i.e., survival curves similar to those obtained when
      treating single-cell suspensions. C. perniciosa had significantly higher UVC
      resistance than haploid bakers yeast but was more sensitive to 4NQO and extremely
      sensitive to PAQ and H2O2 when compared to likewise-treated yeast. Haploid C.
      perniciosa basidiospores (monokaryotic) were significantly more UVC resistant
      than C. perniciosa broken hyphae and than haploid and diploid yeast wild-type
      strains. This suggests a high capacity in C. perniciosa for repair of UVC-induced
      DNA lesions or, alternatively, an efficient protection from UVC irradiation,
      especially in basidiospores. The pronounced sensitivity of the dikaryotic form of
      C. perniciosa to PAQ and H2O2 points to a weak protection from oxidative stress
      inducing agents.

PMID- 16586020
TI  - Genotypic characterization and phylogenetic relations of Pseudomonas sp.
      (Formerly P. stutzeri) OX1.
AB  - Pseudomonas sp. OX1, an aromatic compound-degrading bacterium that was
      tentatively identified by conventional biochemical methods as P. stutzeri, has
      now been investigated at the molecular level to clarify its taxonomic position.
      Amplified ribosomal DNA restriction analysis and multiple enzyme restriction
      fragment length polymorphism (MERFLP) analysis suggested that Pseudomonas sp. OX1
      could not be classified as P. stutzeri. Phylogenetic analyses based on 16S rRNA
      and gyrB genes further confirmed that this strain belongs to the Pseudomonas
      (sensu stricto) genus, but not to the stutzeri species. The data obtained
      demonstrated that Pseudomonas sp. OX1 belongs to intrageneric cluster II and is
      related to the P. fluorescens-P. syringae complex.

PMID- 16586021
TI  - Rhizobium-mediated induction of phenolics and plant growth promotion in rice
      (Oryza sativa L.).
AB  - Qualitative and quantitative estimation of phenolic compounds was done through
      reverse phase-high performance liquid chromatography (RP-HPLC) from different
      parts (leaf, stem, and root) of rice plants after inoculation with two rhizobial
      strains, RRE6 (Rhizobium leguminosarum bv. phaseoli) and ANU 843 (R.
      leguminosarum bv. trifolii) and infection by Rhizoctonia solani. On the basis of
      their retention time, the major phenolic acids detected in HPLC analysis were
      gallic, tannic, ferulic, and cinnamic acids. Furthermore, in all Rhizobium
      inoculated rice plants, synthesis of phenolic compounds was more consistently
      enhanced than in control (uninoculated plants), where the maximum accumulation of
      phenolic compounds was observed in plants inoculated with RRE6 and infection with
      R. solani. Under pathogenic stress, RRE6 performed better because a relatively
      higher amount of phenolics was induced as compared with plants treated with ANU
      843. Phenolic acids mediate induced systemic resistance and provide bioprotection
      to plants during pathogenic stresses. In addition, both rhizobial strains promote
      growth and productivity of rice plants in greenhouse conditions. This report on
      Rhizobium-mediated defense responses and growth promotion of nonlegume (such as
      rice) provides a novel paradigm of symbiotic plant-microbe interaction.

PMID- 16586023
TI  - Proteinase activity of prevotella species associated with oral purulent
      infection.
AB  - Prevotella intermedia and Prevotella nigrescens are often regarded as principal
      causes of acute dentoalveolar infection; however, other species within the genus
      are also known to be associated with such infection. The aim of this study was to
      determine the in vitro proteolytic activity of these different Prevotella species
      that have been implicated with dentoalveolar infection. A total of 234 strains
      were obtained from pus specimens from dentoalveolar infection and from the plaque
      of healthy volunteers. Prevotella loescheii, Prevotella oralis, Prevotella
      melaninogenica, Prevotella buccae, and Prevotella denticola were all shown to
      have a proteolytic activity (8.5-10.5 x 10(-8) A-units) lower than that of P.
      intermedia and P. nigrescens (21.1-23.5 x 10(-8) A-units). In the case of P.
      loescheii, P. melaninogenica, and P. intermedia, the level of proteolytic
      activity for clinical strains was significantly (P < 0.05) higher than that
      recorded for commensal strains. Proteolytic activity for all species of
      Prevotella examined was inhibited by N-ethylmaleimide and phenymethylsulfonyl
      fluoride. This study suggests that Prevotella species associated with oral
      purulent infection produce cysteine and serine proteinases and that in certain
      species of Prevotella, the strains involved in infection exhibit higher
      proteolytic activity when compared with strains from healthy sites.

PMID- 16586022
TI  - Evaluation of herpes simplex detection in corneal scrapings by three molecular
      methods.
AB  - Herpes simplex virus (HSV)-1 keratitis (HSK) is a sight-threatening ocular
      infection with worldwide occurrence. A prompt laboratory diagnosis is often very
      useful. The purpose of this study was to evaluate molecular methods as rapid
      diagnostic tools compared with cell culture of HSK. Corneal scrapings from
      patients with clinically suspected HSK were tested by direct immunofluorescence
      assay (IFA) for HSV-1 antigen and by polymerase chain reaction (PCR) for HSV-1
      DNA, and an attempt for viral isolation was performed on Vero cell line culture.
      Positive samples by cell culture were 20.8%, whereas PCR was positive in 29.2%,
      and IFA was positive in 33.3%. IFA had better sensitivity (80%) and negative
      predictive value (81.8%) than PCR (70% and 76.9%, respectively); however, PCR had
      better specificity (71.4%) and positive predictive value (63.6%). This indicates
      that a combination of cell culture, IFA and PCR constitutes the best set of tools
      for diagnosis of clinically suspected cases of HSK. Documented infection can be
      further assessed by cell-culture technique or PCR depending laboratory
      availability.

PMID- 16586024
TI  - Bacteriocins Pep5 and epidermin inhibit Staphylococcus epidermidis adhesion to
      catheters.
AB  - Pep5 and epidermin bacteriocins were tested on clinical strains of Staphylococcus
      epidermidis and S. aureus isolated from catheter-related infections. These
      bacteriocins were inhibitory to several isolates at a concentration of 640
      activity units mL(-1). The ability of bacteriocins in inhibiting adhesion of S.
      epidermidis to silicone catheters was evaluated. When Pep5 and epidermin were
      added to in vitro catheter colonization experiments, there was a significant
      decrease in the cell number of S. epidermidis adhered to silicone catheters.
      Bacteriocins used to decrease bacterial attachment to medical devices may
      represent a novel strategy to control catheter-related infections.

PMID- 16586025
TI  - Isolation and identification of natural endophytic rhizobia from rice (Oryza
      sativa L.) through rDNA PCR-RFLP and sequence analysis.
AB  - Three novel endophytic rhizobial strains (RRE3, RRE5, and RRE6) were isolated
      from naturally growing surface-sterilized rice roots. These isolates had the
      ability to nodulate common bean (Phaseolus vulgaris). Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and sequencing of 16S rDNA of
      these isolates revealed that RRE3 and RRE5 are phylogenetically very close to
      Burkholderia cepacia complex, whereas RRE6 has affinity with Rhizobium
      leguminosarum bv. phaseoli. Plant infection test using gusA reporter gene-tagged
      construct of these isolates indicated that bacterial cells can go inside and
      colonize the rice root interiors. A significant increase in biomass and grain
      yield was also recorded in greenhouse-grown rice plants inoculated with these
      isolates.

PMID- 16586026
TI  - Accelerated degradation of dipentyl phthalate by Fusarium oxysporum f. sp. pisi
      cutinase and toxicity evaluation of its degradation products using bioluminescent
      bacteria.
AB  - The efficiency of two lipolytic enzymes (fungal cutinase and yeast esterase) in
      the degradation of dipentyl phthalate (DPeP) was investigated. The DPeP
      degradation rate of fungal cutinase was surprisingly high, i.e., almost 60% of
      the initial DPeP (500 mg/L) was decomposed within 2.5 hours, and nearly 40% of
      the degraded DPeP disappeared within the initial 15 minutes. With the yeast
      esterase, despite the same concentration, >87% of the DPeP remained even after 3
      days of treatment. The final chemical composition after 3 days was significantly
      dependent on the enzyme used. During degradation with cutinase, most DPeP was
      converted into 1,3-isobenzofurandione (IBF) by diester hydrolysis. However, in
      the degradation by esterase, pentyl methyl phthalate, in addition to IBF, was
      produced in abundance. Toxicity monitoring using various recombinant
      bioluminescent bacteria showed that the degradation products from yeast esterase
      contained a toxic hazard, causing oxidative stress and damage to protein
      synthesis.

PMID- 16586027
TI  - Factors affecting perioperative mortality and wound-related complications
      following major lower extremity amputations.
AB  - Major lower extremity amputations continue to be associated with significant
      morbidity and mortality, yet few recent large series have evaluated factors
      associated with perioperative mortality and wound complications. The purpose of
      this study was to examine factors affecting perioperative mortality and wound
      related complications following major lower extremity amputation. A retrospective
      review was conducted of all adult patients who underwent nontraumatic major lower
      extremity amputations over a 5-year period at a single tertiary-care center in
      southern West Virginia. Demographic and clinical data, perioperative data, and
      outcomes were collected and analyzed to identify any relationship with
      perioperative mortality, as well as wound complications and early revisions
      (within 90 days) to a more proximal level. Variables were examined using chi
      squared, two-tailed t-tests, and logistic regression. Three hundred eighty
      patients (61% male) underwent 412 major lower extremity amputations during 1999
      2003. The initial level of amputation included 230 below-knee (BKA), 149 above
      knee (AKA), and one hip disarticulation. Perioperative mortality was 15.5% (n =
      59). From a regression model, age, albumin level, AKA, and lack of a previous
      coronary artery bypass graft (CABG) were independently related to mortality.
      Patients who did not have a previous CABG were nearly three times more likely to
      die than those who did (p = 0.038). Overall early wound complications were noted
      in 13.4% (n = 51). Four factors were independently related to experiencing a 90
      day wound complication: BKA, community (rather than care facility) living, type
      of anesthesia, and preoperative hematocrit >30%. Major lower extremity amputation
      in patients with peripheral vascular disease continues to be associated with
      considerable perioperative morbidity and mortality. Even though the surgical
      procedure itself may not be challenging from a technical standpoint, underlying
      medical conditions put this group at high risk for perioperative death. Wound
      healing problems are frequently encountered and must be minimized to facilitate
      early mobilization and hospital discharge.

PMID- 16586028
TI  - Spontaneous Iliac vein rupture: case report and comprehensive review of the
      literature.
AB  - Iliac vein rupture is a rare cause of retroperitoneal hemorrhage. It is
      occasionally lethal, with no clear precipitating factors. We report a case of
      spontaneous left common iliac vein rupture in a 56-year-old man with a history of
      deep vein thrombophlebitis (DVT). To date, 32 cases have been reported in the
      literature. The 32 existing cases and the case presented here were analyzed. A
      comparative review was performed for chief complaints, basic demographics,
      potential predisposing factors, treatment modalities, and outcomes. Possible
      etiological factors to explain this phenomenon were formulated. The patient
      presented with abdominal pain of 4 hr duration and a near-syncope episode. In the
      emergency room, he was found to be in hypovolemic shock that was responsive to
      crystalloids. An urgent exploratory laparotomy was performed for a suspected
      iliac artery rupture. An uncontrollable hemorrhage from a spontaneous
      posteromedial tear of the left common iliac vein resulted in intraoperative
      death. Interestingly, 85% of reported cases occurred in women with an overall
      average age of 60.6 +/- 13.4 years; 94% of cases were left-sided; 79% reported
      clinical or histological evidence of DVT or thrombophlebitis; 94% were treated
      operatively, with a survival rate of 71%. Only one reported case was treated
      conservatively, with success, and one reported case of endovascular repair
      resulted in significant morbidity. Iliac vein rupture is an uncommon diagnosis
      associated with trauma and even rarer when it is spontaneous. We report the
      thirty-third documented case in the literature since 1961. There is a clear
      predominance in females and on the left side and a probable association with
      thrombophlebitis. Our calculated operative success may be overestimated due to a
      biased literature reporting of favorable outcomes.

PMID- 16586029
TI  - [Sigismund Albicus (ca. 1358-1427). The first "rheumatologist" at the Charles
      University in Prague].

PMID- 16586030
TI  - Anatomy of the hypophysiotropic somatostatinergic and growth hormone-releasing
      hormone system minireview.
AB  - The central control of growth hormone (GH) secretion from the pituitary gland is
      ultimately achieved by the interaction between two hypothalamic neurohormones,
      somatostatin which inhibits and growth hormone-releasing hormone (GHRH) which
      stimulates GH release. The regulation of the somatostatin and GHRH release from
      the hypothalamus is regulated by a range of other neuropeptides,
      neurotransmitters, neurohormones. In this mini review we attempt to provide a
      short summary covering the anatomy and chemical characteristics of the various
      cell populations regulating GH secretion as a tribute to Miklos Palkovits who
      pioneered the field of functional neuroanatomy of hypothalamic networks.

PMID- 16586031
TI  - A short estrogen-responsive N-terminal galanin homologue found in rat brain and
      gut with antiserum raised against rat galanin(1-16).
AB  - Galanin-like peptide (GALP) is currently the only known galanin(1-29) homologue.
      However, three different galanin receptors, of which GalR3 exhibits comparatively
      low affinity for galanin(1-29), and molecular heterogeneity of immunoreactive
      galanin are arguments for presence of other endogenous galanin homologues. Since
      antibodies recognize three-dimensional structures of 3-5 amino acids in a
      peptide, we raised antibodies in rabbits against galanin(1-16) conjugated to
      bovine serum albumin, looking for the presence of endogenous N-terminal galanin
      homologues in rat tissues. The antiserum selected had 7,830 times higher avidity
      for galanin(1-16) compared to galanin(1-29). A single immunoreactive component
      with a Stokes radius of about 8 amino acids was found. Immunohistochemistry
      strongly suggested that this immunoreactivity is localised in the same neurons as
      galanin(1-29). Furthermore, its concentration was increased in response to
      estrogen treatment in the same brain regions as galanin(1-29), although not as
      rapidly. The present results indicate the presence of a novel endogenous N
      terminal galanin homologue.

PMID- 16586033
TI  - Ethanol and (-)-alpha-pinene: attractant kairomones for some large wood-boring
      beetles in southeastern USA.
AB  - Ethanol and alpha-pinene were tested as attractants for large wood-boring pine
      beetles in Alabama, Florida, Georgia, North Carolina, and South Carolina in 2002
      2004. Multiple-funnel traps baited with (-)-alpha-pinene (released at about 2 g/d
      at 25-28 degrees C) were attractive to the following Cerambycidae: Acanthocinus
      nodosus, A. obsoletus, Arhopalus rusticus nubilus, Asemum striatum, Monochamus
      titillator, Prionus pocularis, Xylotrechus integer, and X. sagittatus sagittatus.
      Buprestis lineata (Buprestidae), Alaus myops (Elateridae), and Hylobius pales and
      Pachylobius picivorus (Curculionidae) were also attracted to traps baited with (
      )-alpha-pinene. In many locations, ethanol synergized attraction of the
      cerambycids Acanthocinus nodosus, A. obsoletus, Arhopalus r. nubilus, Monochamus
      titillator, and Xylotrechus s. sagittatus (but not Asemum striatum, Prionus
      pocularis, or Xylotrechus integer) to traps baited with (-)-alpha-pinene.
      Similarly, attraction of Alaus myops, Hylobius pales, and Pachylobius picivorus
      (but not Buprestis lineata) to traps baited with (-)-alpha-pinene was synergized
      by ethanol. These results provide support for the use of traps baited with
      ethanol and (-)-alpha-pinene to detect and monitor common large wood-boring
      beetles from the southeastern region of the USA at ports-of-entry in other
      countries, as well as forested areas in the USA.

PMID- 16586032
TI  - Chemical defenses promote persistence of the aquatic plant Micranthemum umbrosum.
AB  - Five of the most common macrophytes from an aquaculture facility with high
      densities of the herbivorous Asian grass carp (Ctenopharyngodon idella) were
      commonly unpalatable to three generalist consumers-grass carp and the native
      North American crayfishes Procambarus spiculifer and P. acutus. The rooted
      vascular plant Micranthemum umbrosum comprised 89% of the total aboveground plant
      biomass and was unpalatable to all three consumers as fresh tissues, as
      homogenized pellets, and as crude extracts. Bioassay-guided fractionation of the
      crude extract from M. umbrosum led to four previously known compounds that each
      deterred feeding by at least one consumer: 3,4,5-trimethoxyallylbenzene (1) and
      three lignoids: beta-apopicropodophyllin (2); (-)-(3S,4R,6S)-3-(3',4'
      methylenedioxy-alpha-hydroxybenzyl)-4-(3'',4''-dimethoxybenzyl)butyrolactone (3);
      and (-)-hibalactone (4). None of the remaining four macrophytes produced a
      chemically deterrent extract. A 16-mo manipulative experiment showed that the
      aboveground biomass of M. umbrosum was unchanged when consumers were absent, but
      the biomass of Ludwigia repens, a plant that grass carp preferentially consumed
      over M. umbrosum, increased over 300-fold. Thus, selective feeding by grass carp
      effectively eliminates most palatable plants from this community and promotes the
      persistence of the chemically defended M. umbrosum, suggesting that plant
      defenses play critical yet understudied roles in the structure of freshwater
      plant communities.

PMID- 16586034
TI  - Experience induces a phytophagous insect to lay eggs on a nonhost plant.
AB  - Experience of nonhost plants by phytophagous insects may alter their foraging and
      oviposition responses to these plants. Using the diamondback moth (DBM) Plutella
      xylostella (L.), its host-plant Chinese cabbage, and a nonhost-plant Pisum
      sativum (pea) as a model system, we examined whether experience of the nonhost
      plant by adults can induce oviposition on the nonhost plant. Naive DBM females
      did not accept pea for oviposition in either no-choice or choice conditions,
      whereas females with prior experience of pea laid up to 20% of their eggs on this
      plant. Naive females reduced their oviposition, but experienced females did not
      refrain from laying eggs in a nonhost-plant environment. Such habituation to
      nonhost plants could lead to host range expansion in phytophagous insects and
      increase mortality of pest insects in diversified crop systems.

PMID- 16586035
TI  - Beyond 9-ODA: sex pheromone communication in the European honey bee Apis
      mellifera L.
AB  - The major component of the mandibular gland secretion of queen honeybees (Apis
      mellifera L.), 9-ODA ((2E)-9-oxodecenoic acid), has been known for more than 40
      yr to function as a long-range sex pheromone, attracting drones at congregation
      areas and drone flyways. Tests of other mandibular gland components failed to
      demonstrate attraction. It remained unclear whether these components served any
      function in mating behavior. We performed dual-choice experiments, using a
      rotating drone carousel, to test the attractiveness of 9-ODA compared to mixtures
      of 9-ODA with three other most abundant components in virgin queen mandibular
      gland secretions: (2E)-9-hydroxydecenoic acid (9-HDA), (2E)-10-hydroxydecenoic
      acid (10-HDA), and p-hydroxybenzoate (HOB). We found no differences in the number
      of drones attracted to 9-ODA or the respective mixtures over a distance. However,
      adding 9-HDA and 10-HDA, or 9-HDA, 10-HDA, and HOB to 9-ODA increased the number
      of drones making contact with the baited dummy. On the basis of these results, we
      suggest that at least 9-HDA and 10-HDA are additional components of the sex
      pheromone blend of A. mellifera.

PMID- 16586036
TI  - Dimethylfuran-lactone pheromone from males of Galerucella calmariensis and
      Galerucella pusilla.
AB  - Male Galerucella calmariensis and Galerucella pusilla (Coleoptera: Chrysomelidae)
      emit an aggregation pheromone while feeding on host foliage. Isolation of the
      compound from collected volatiles was guided by comparisons of gas chromatograms
      of extracts from males and females and by gas chromatography
      electroantennographic detection. The compound was identified by a combination of
      spectrometric methods and microchemical tests as the novel dimethylfuran lactone,
      12,13-dimethyl-5,14-dioxabicyclo[9.2.1]tetradeca-1(13),11-dien-4-one. The
      structure was confirmed by synthesis, and the synthetic compound attracted males
      and females of both species in field bioassays. These beetles were previously
      introduced into North America as biological control agents for the invasive
      wetland weed, purple loosestrife Lythrum salicaria, and the pheromone could
      become a tool for monitoring populations. A new method is described for
      distinguishing the two species based on the tibial spurs of the males.

PMID- 16586037
TI  - Attraction of Piezodorus hybneri to the aggregation pheromone components of
      Riptortus clavatus.
AB  - The aggregation pheromone of Riptortus clavatus (Heteroptera: Alydidae) consists
      of (E)-2-hexenyl (Z)-3-hexenoate (E2HZ3H), (E)-2-hexenyl (E)-2-hexenoate
      (E2HE2H), and myristyl isobutyrate (MI). Experiments were conducted to examine
      the attraction of Piezodorus hybneri (Heteroptera: Pentatomidae) to the pheromone
      components of R. clavatus, individually and in combination, and to determine if
      P. hybneri produces these compounds. Electroantennogram (EAG) responses of P.
      hybneri to E2HE2H were significant in a dose dependent manner, while those to
      E2HZ3H were not significantly different from those to hexane and air. Field
      trapping tests using E2HZ3H, E2HE2H, and MI, individually or in combination,
      showed that only E2HE2H was attractive to P. hybneri. E2HE2H was not detected in
      whole-body extracts or volatile collections from either sex of P. hybneri adults.
      We propose that the response of P. hybneri adults to the R. clavatus aggregation
      pheromone may be related to finding suitable host plants.

PMID- 16586038
TI  - Epicuticular factors involved in host recognition for the aphid parasitoid
      Aphidius rhopalosiphi.
AB  - In insect parasitoids, fitness is dependent on the host finding and recognition
      abilities of the female. Host recognition cues have been described for various
      host-parasitoid systems, but are still under investigation in aphid parasitoids.
      Our study aimed to clarify the respective role of physical and chemical cues in
      recognition of the aphid cuticle. Shed aphid exuviae were used as an elicitor in
      order to avoid any influence of color, movement, or volatiles present in a living
      aphid. We assessed the effect of chemical and heat treatments on the texture of
      the cuticle by using scanning electron microscopy and tested the recognition of
      treated cuticles by the parasitoid. We showed that recognition cues of the
      cuticle can be removed chemically (using combined treatments with n-hexane and
      methanol). Moreover, heat treatment destroyed the physical texture of the cuticle
      without significantly reducing parasitoid recognition. In a second step, we
      showed that epicuticular extracts deposited on pieces of paper triggered female
      attack behavior. First results concerning the chemical composition of the active
      extract are presented. This study shows that chemical compounds extractable by
      organic solvents mediate cuticle recognition by aphid parasitoids.

PMID- 16586039
TI  - Leaf epicuticular wax chemicals of the Japanese knotweed Fallopia japonica as
      oviposition stimulants for Ostrinia latipennis.
AB  - Extraction, fractionation, and gas chromatography-mass spectrometry analyses
      guided by bioassays have shown that n-alkanes and free fatty acids in leaf
      epicuticular wax of the Japanese knotweed Fallopia (Reynoutria) japonica
      stimulate oviposition in the Far-Eastern knotweed borer, Ostrinia latipennis
      (Lepidoptera: Crambidae). n-Alkanes made up 48.1% of the total amount of
      epicuticular wax, and their carbon chain length was in the C(16)-C(33) range,
      with n-nonacosane (n-C(29)) most abundant, followed by n-C(27), n-C(25), and n
      C(31). Free fatty acids with C(9)-C(22) accounted for 22.3%, and hexadecanoic
      acid was predominant. A mixture of authentic n-alkanes and fatty acids of the
      composition found in the epicuticular wax, a mixture of n-alkanes, and a mixture
      of fatty acids significantly enhanced oviposition. Thus, it was demonstrated that
      both n-alkanes and free fatty acids in leaf epicuticular wax of F. japonica are
      naturally occurring oviposition stimulants for O. latipennis.

PMID- 16586040
TI  - Hard clams (Mercenaria mercenaria) evaluate predation risk using chemical signals
      from predators and injured conspecifics.
AB  - Hard clams, Mercenaria mercenaria, are sessile, filter-feeding organisms that are
      heavily preyed upon by blue crabs, which find their clam prey using chemical
      cues. Clams may evade blue crabs by reducing their pumping (feeding) behavior
      when a threat is perceived. The purpose of this study was to determine the type
      of signals that clams use to detect consumers. Clams decreased their pumping time
      in response to blue crabs and blue crab effluent, but not to crab shells,
      indicating that chemical signals and not mechanical cues mediated the response of
      clams to distant predators. Because predator diet can influence prey evaluation
      of predatory threats, we compared clam responses to blue crabs fed a steady diet
      of fish, clams, or that were starved prior to the experiment. In addition, we
      used injured clams as a stimulus because many organisms detect predators by
      sensing the odor of injured con- or heterospecifics. Clams reduced feeding in
      response to injured conspecifics and to blue crabs that had recently fed. Clams
      reacted similarly to fed crabs, regardless of their diet, but did not respond to
      starved blue crabs. Because blue crabs are generalist predators and the threat
      posed by these consumers is unrelated to the crab's diet, we should expect clam
      reactions to blue crabs to be independent of the crab's diet. The failure of
      clams to react to starved blue crabs likely increases their vulnerability to
      these consumers, but clam responses to injured conspecifics may constitute a
      strategy that allows animals to detect an imminent threat when signals emanating
      from blue crabs are not detectable.

PMID- 16586041
TI  - Heritable variation in the sex pheromone of the almond moth, Cadra cautella.
AB  - The sex pheromone of the female almond moth, Cadra cautella, constitutes a highly
      variable signal. Age and period of the L/D cycle had significant effects on the
      variation in titers of (Z,E)-9,12-tetradecadienyl acetate (Z9,E12-14:Ac) and (Z)
      9-tetradecenyl acetate (Z9-14:Ac) and the ratio of Z9,E12-14:Ac to Z9-14:Ac.
      Across age classes, minimum and maximum mean titers (ng +/- SE) of Z9,E12-14:Ac
      and Z9-14:Ac ranged from 8.7 +/- 0.46 to 21 +/- 1.0 and from 2.0 +/- 0.14 to 2.9
      +/- 0.15, respectively; the mean ratio of Z9,E12-14:Ac to Z9-14:Ac ranged from
      5.2 +/- 0.21 to 11 +/- 0.40. The titers of Z9,E12-14:Ac and Z9-14:Ac and the
      ratio of Z9,E12-14:Ac to Z9-14:Ac were highest at the onset of the scotophase and
      lowest at the onset of the photophase. Similarly, the titer of Z9,E12-14:Ac and
      the ratio of Z9,E12-14:Ac to Z9-14:Ac were highest in females sampled 1 d
      postemergence and declined over all age classes. The titer of Z9-14:Ac increased
      from day 1 to day 2, and then declined to levels equivalent to day 1. Analysis of
      pupal and adult mass demonstrated a positive correlation (r = 0.874, P < 0.001);
      however, the titer of neither Z9,E12-14:Ac or Z9-14:Ac nor the ratio of Z9,E12
      14:Ac to Z9-14:Ac were significantly correlated with pupal mass. Age-related
      variations in pheromone titer and ratios were heritable. The narrow-sense
      heritability of the observed variation in 1-d-old females, 1 hr into the
      scotophase is 1.2 +/- 0.32, 0.75 +/- 0.24, and 0.46 +/- 0.17 for the titer of
      Z9,E12-14:Ac and Z9-14:Ac and the ratio of Z9,E12-14:Ac to Z9-14:Ac,
      respectively. A significant additive genetic correlation was observed between
      that of Z9,E12-14:Ac and Z9-14:Ac, but not between that of either Z9,E12-14:Ac or
      Z9-14:Ac and the ratio of Z9,E12-14:Ac to Z9-14:Ac. The results of the genetic
      analyses suggest that the traits of titer of Z9,E12-14:Ac and Z9-14:Ac have a
      greater potential to respond to selection than the trait of ratio of Z9,E12-14:Ac
      to Z9-14:Ac.

PMID- 16586042
TI  - Tacrolimus and cyclosporine A inhibit human osteoclast formation via targeting
      the calcineurin-dependent NFAT pathway and an activation pathway for c-Jun or
      MITF in rheumatoid arthritis.
AB  - In the present study, we aimed to determine whether tacrolimus (FK506) and
      cyclosporine A act directly on human osteoclast precursors obtained from patients
      with rheumatoid arthritis (RA) and influence monocyte-osteoclast differentiation
      induced by receptor activator of NF-kappaB ligand (RANKL) in vitro, the stage at
      which differentiation was affected and the manner in which tacrolimus or
      cyclosporine A affected the osteoclast signaling pathway. Peripheral blood
      mononuclear cells (PBMCs) were isolated from RA patients and cultured in the
      presence of RANKL and macrophage-colony stimulating factor (M-CSF). Tacrolimus or
      cyclosporine A was added to these cultures to determine the effect on the
      osteoclast differentiation. Osteoclast formation was determined by assessing the
      number of tartrate resistant acid phosphatase (TRAP) staining cells and measuring
      the extent of lacunar resorption. The expression of osteoclast transcription
      factors, such as TNF receptor-associated factor 6 (TRAF6), nuclear factor of
      activated T cells c1 (NFATc1), c-Fos, c-Jun, microphthalmia transcription factor
      (MITF) and PU.1 in mononuclear cells (MNCs) was assayed by quantitative reverse
      transcription-polymerase chain reaction. Addition of tacrolimus or cyclosporine A
      resulted in a decrease in the number of TRAP-positive multinucleated cells (TRAP+
      MNCs) and a decrease in the extent of lacunar resorption pit formation as
      compared to the control cultures; thus, human monocyte-osteoclast differentiation
      was more effectively inhibited at the late stage and addition of tacrolimus or
      cyclosporine A resulted in a decrease in the mRNA expression of NFATc1, c-Jun,
      and MITF at the late stage. Our results suggest that tacrolimus or cyclosporine A
      acts directly on human osteoclast precursors in RA patients and exerts their
      immunosuppressive effects on human monocyte-osteoclast formation via targeting
      both the calcineurin-dependent NFAT pathway and activation pathway for c-Jun or
      MITF.

PMID- 16586043
TI  - Recurrent congenital heart block in neonatal lupus.
AB  - Congenital heart block (CHB) is the main complication of neonatal lupus (NL) and
      is strongly associated with the presence of anti-SSA/Ro and anti-SSB/La
      antibodies. The recurrence of CHB in subsequent pregnancies in mothers with these
      antibodies is uncommon, occurring in approximately 15% of cases. We describe here
      a case of recurrent CHB in a previously asymptomatic mother with Sjogren syndrome
      and discuss the current strategies for the prevention and treatment of CHB in NL.

PMID- 16586044
TI  - Childhood vasculitides in Turkey: a nationwide survey.
AB  - AIM: The aims of this study were to evaluate the characteristics of childhood
      vasculitides and to establish the first registry in Turkey, an eastern
      Mediterranean country with a white population. PATIENTS AND METHODS: A
      questionnaire was distributed to the main referral centers asking for the
      registration of the Henoch-Schonlein purpura (HSP) patients in the last calendar
      year only and 5 years for other vasculitides. Demographic, clinical, and
      laboratory data were assessed. RESULTS: Vasculitic diseases were registered from
      15 pediatric centers. These centers had a fair representation throughout the
      country. In the last calendar year, incidences were as follows: HSP 81.6%,
      Kawasaki disease (KD) 9.0%, childhood polyarteritis nodosa (C-PAN) 5.6%, Takayasu
      arteritis (TA) 1.5%, Wegener's granulomatosis 0.4%, and Behcet disease 1.9%.
      There was no clear gender dominance. The mean age was 11.05+/-4.89 years. Acute
      phase reactants were elevated in almost all, highest figures being in C-PAN.
      Renal involvement was present in 28.6% of HSP and 53% of the C-PAN patients.
      Abdominal aorta was involved in all TA patients. Among the C-PAN patients, 25%
      had microscopic PAN with necrotizing glomerulonephritis; antineutrophil
      cytoplasmic antibody was positive in those who were studied. Among the patients,
      12.5% and 15% had classic PAN and cutaneous PAN, respectively. The remaining
      majority were classified as systemic C-PAN diagnosed with biopsies and/or
      angiograms demonstrating small to midsize artery involvement. The overall
      prognosis was better than reported in adult series. CONCLUSION: This is the
      largest multicenter study defining the demographic data for childhood
      vasculitides. The distribution of childhood vasculitides was different in our
      population where KD is much less frequent, whereas HSP constitutes an
      overwhelming majority. C-PAN was more frequent as well.

PMID- 16586045
TI  - Chronic monoarthritis and previous history of cancer: think about synovial
      metastasis.
AB  - Synovial metastases are rare events. Only 37 cases diagnosed by synovial fluid
      cytologic examination and/or by microscopic investigation of synovial biopsies
      have been previously reported in the literature. We report another case of
      shoulder chronic arthritis due to a recurrence of rectal adenocarcinoma and
      review previous published observations. Generally, this condition carries a poor
      prognosis with average patients survival of less than 5 months. The possibility
      of metastatic disease should be considered when an elderly person or patient with
      a history of previous malignancy presents with a chronic arthritis.

PMID- 16586047
TI  - A still image of a transient rash captured by a mobile phone.
AB  - The diagnosis of adult onset Still's disease (AOSD) can be difficult as the
      differential diagnosis is broad, it is based on clinical criteria and the signs,
      for example rash, can be transient. Clinical photography has an obvious role, and
      with modern technology, is now in the hands of physicians. We report a case of
      AOSD where an image of a transient rash taken with a camera phone allowed the
      diagnosis to be established. Further, we discuss the controversies around
      hospital bans on mobile phones (due to potential incompatibility with medical
      devices) and the reality of their widespread use. We conclude that, providing
      safeguards of consent and data storage are in place, the camera phone is a useful
      tool in rheumatology practice.

PMID- 16586046
TI  - Delayed diagnosis of systemic lupus erythematosus due to lack of competency
      skills in musculoskeletal examination.
AB  - Deficiencies in musculoskeletal (MSK) examination skills among internal medicine
      residents can cause serious outcomes. We report a case of systemic lupus
      erythematosus with active arthritis where the diagnosis was delayed for 7 days
      after hospital admission due to the lack of basic skills in MSK examination.

PMID- 16586050
TI  - Adrenal angiomyolipoma in lymphangioleiomyomatosis.

PMID- 16586051
TI  - [Ureteroscopy (URS) for ureteric calculi].
AB  - Distal ureteral calculi (<5 mm) usually pass the ureter spontaneously.
      Ureteroscopic lithotripsy of distal ureteral calculi shows high stone-free rates
      with a low complication rate (4%) and is equal to extracorporeal shock wave
      lithotripsy (ESWL), while ESWL is the primary choice for proximal ureteric
      stones. Flexible endoscopes are more difficult to handle and should be used only
      under fluoroscopic control. They are generally used in combination with the
      holmium:YAG laser and the flexible Lithoclast in the proximal ureter or the renal
      collecting system. Overall the complication rate of URS is 9-11% with avulsion of
      the ureteric urothelium being the most common complication. Ureteral perforation,
      stricture (<1%), impaction of the instrument in the ureter with consequent
      ureteral laceration, extravasation of stones, and bleeding in the urogenital
      tract are complications of URS but are minimal in the hands of a well-trained and
      skilled surgeon.

PMID- 16586048
TI  - Plant originated glycoprotein has anti-oxidative and anti-inflammatory effects on
      dextran sulfate sodium-induced colitis in mouse.
AB  - We investigated the preventive effect of glycoprotein (27 kDa) isolated from
      Gardenia jasminoides Ellis (GJE) fruits on colitis in dextran sulfate sodium
      (DSS, 3%)-induced A/J mice which were administrated orally for 7 days. Anti
      inflammatory activity of GJE glycoprotein was assessed by neutrophil infiltration
      and colonic lipid peroxidation, and determined by myeloperoxidase (MPO) activity
      and levels of thiobarbituric acid reactive substances (TBARS), respectively in
      DSS treatment system. The activities of antioxidative enzymes [catalase (CAT),
      superoxide dismutase (SOD), and glutathione peroxidase (GPx)], activation of
      inflammation related mediators (iNOS, COX-2, and NF-kappaB), and production of
      nitric oxide (NO) and reactive oxygen species (ROS) were also measured. The
      results of this study showed that GJE glycoprotein (80 microg/ml) has a
      scavenging property to inhibit the intracellular ROS production in RAW 264.7
      cells and that GJE glycoprotein (80 mg/kg BW) significantly suppressed the
      increase in the MPO activity, TBARS level, and NO production, inflammation
      related mediators [iNOS, COX-2, and NF-kappaB (p50)] activity in DSS-induced
      mice. Interestingly, the activities of CAT, SOD, and GPx were gradually augmented
      after a supplement of GJE glycoprotein. Therefore, we suggest that GJE
      glycoprotein is preventive and therapeutic agent for the ulcerative colitis.

PMID- 16586052
TI  - [Sentinel lymph node dissection in prostate cancer. Experience after more than
      800 interventions].
AB  - There is no consensus on which prostate cancer patients should undergo lymph node
      removal and which lymph nodes should be included. Therefore, most clinicians rely
      on nomograms and dispense with lymph node dissection in patients with low-risk
      disease. Meanwhile, there are some studies which prove that there are also lymph
      node metastases in patients with low-risk prostate cancer and that lymph node
      metastases are predominantly localized outside the region of standard
      lymphadenectomy. In more than 800 men we could show that lymph node metastases
      were found more often than shown in the Partin tables. These lymph node
      metastases were detected by sentinel lymph node dissection outside the region of
      standard and extended lymphadenectomy. Because of insufficient preoperative
      diagnostics it is unclear which patients have positive lymph nodes. Therefore, it
      is useful to perform lymph node dissection in every patient. Men with positive
      nodes could have a better prognosis, when sentinel and extended lymph node
      dissection are performed.

PMID- 16586053
TI  - [Psychosocial aspects of interstitial cystitis. Do biographical factors have a
      relevant impact on the disease course?].
AB  - BACKGROUND: The present study explores the influence of psychosocial adversities
      on the etiology and progress of interstitial cystitis (IC). METHODS: A systematic
      survey of the childhood risk factors was carried out using a specially developed,
      structured interview for pain patients (MSBA-Mainzer Strukturierte Biographische
      Anamnese) and additionally the Brief Symptom Inventory (BSI). Essentially a
      descriptive evaluation was performed. Thirty IC patients who fulfilled the
      current diagnostic criteria participated in the study. RESULTS: The investigation
      showed higher values for relevant childhood adversities in IC patients. A poor
      emotional relationship with both parents, chronic diseases of the parents, and
      physical maltreatment were frequently reported. In the cumulative adverse
      childhood experience score IC patients showed higher levels than published data
      of healthy control groups. The contemporary social history did not show relevant
      psychosocial adversities. The quality of life is extremely reduced because of IC
      symptoms. The BSI showed high levels especially in the dimensions somatization,
      anxiety, and phobic anxiety. CONCLUSION: The results of this study argue for a
      participatory role of psychosomatic factors in the assumed multifactorial
      etiology of interstitial cystitis.

PMID- 16586054
TI  - [Gynaecological and obstetrical aspects of recurrent urinary tract infections].
AB  - The microbial colonization of vulva, vagina and cervix uteri represents the
      reservoir for recurrent urinary tract infection. All bacterial species of normal
      cutaneous or gastrointestinal flora can be found in the external genital tract
      even under physiological conditions. The higher concentration of microbes adds to
      the predisposition for urinary tract infection in cases of dysbiosis or
      inflammation, apart from specific infection by Trichomonas vaginalis, Neisseria
      gonorrhoeae or Chlamydia trachomatis. The specific immunological interaction
      between bacteria and host, i.e. between virulence factors and intrinsic defense,
      appears to be the major mechanism paving the way for recurrent infection. The
      elimination of predisposing factors is the clue for successful therapy as well as
      for prevention of recurrence.

PMID- 16586055
TI  - [Complex proximal humerus fractures--management with a humeral head prosthesis?
      Clinical and radiological results of a prospective study].
AB  - BACKGROUND: Proximal humerus fractures are one of the most common fractures in
      elderly patients. In the treatment of complex proximal humerus fractures, primary
      hemiarthroplasty is still discussed controversially. The present study was
      undertaken to evaluate the results of primary hemiarthroplasty in the treatment
      of proximal humerus fractures with a modular prosthesis (EPOCA, Fa. Argomedical,
      Gifhorn, Germany). MATERIAL AND METHODS: A prospective study of 24 patients with
      complex humerus fracture (NEER: IV/4, V/4, VI/4, and head split fracture) was
      performed from August 2000 to December 2002. Mean age was 75.6 years (range: 52
      92); 18 patients were seen for follow-up after 0.5 and 1 year, respectively. The
      Constant-Murley score (max. 100 points) and the UCLA Rating System (max. 35
      points) were calculated for functional assessment of the operated shoulder.
      RESULTS: Fifteen patients (83%) were pain free 1 year after the operation. The
      Constant-Murley score improved from 52 (+/-17) to 56 (+/-18) at the second follow
      up after 1 year. On the contralateral side a score of 86 (+/-10) was assessed
      (p<0.05 vs operated side). Correspondingly, shoulder function according to the
      UCLA Rating System improved [25 (+/-4); 27 (+/-5)]. CONCLUSIONS: Osteoporotic
      bone of older patients often may not permit stable internal fixation of complex
      proximal humerus fractures. In these situations primary hemiarthroplasty is the
      treatment of choice.

PMID- 16586056
TI  - [Heterotopic hand replantation following radical tumor resection in the elbow
      region. Functional results 15 months after surgery].
AB  - BACKGROUND: In a 28-year-old male who had suffered an olecranon fracture, delayed
      diagnosis was made of epithelioid sarcoma in the left upper extremity. Radical
      tumor resection was carried out which included removal of the entire elbow joint.
      MATERIAL AND METHODS: The amputated hand with the distal one-third of the forearm
      was replanted at the upper arm. It was important to ensure that all tendinous
      structures of the forearm were attached to the three muscles of the upper arm and
      the nerves of the distal forearm with the nerves of the upper arm, which are
      incongruent in diameter with the former. Details of the operation are given
      below. RESULTS: The anatomic peculiarities involved in this form of replantation,
      the early intensive therapy, reintegration of the replanted hand in the body
      scheme, and the usability of such a shortened extremity are described and the
      extremely good functional results documented in numbers and figures.

PMID- 16586057
TI  - [Contrast-enhanced diagnostics in orthopaedics].
AB  - The diagnostic competence of the orthopaedist not only allows him to perform
      adequate therapy concepts, but also to meet the current structural challenges,
      both social and health related. In addition to clinical diagnosis, machine-aided
      diagnosis is becoming more important due to technical advances. In this context,
      contrast-enhanced examination has a special place, as it has an important
      diagnostic advantage in difficult or unclear cases. Current improvements in the
      areas of phlebography, myelography, arthrography and angiography are reviewed.
      Indications, risks and complications as well as the technical procedure are
      critically discussed.

PMID- 16586059
TI  - [Traffic ophthalmology. Assessment of ability to drive in road traffic].
AB  - Assessment of an individual's ability to drive in road traffic is an important
      part of the ophthalmologist's work. It fulfils the ophthalmologist's duty to care
      for the patient and increases general road traffic safety. This assessment
      requires testing of visual acuity, visual field, mesopic vision and glare,
      motility, binocular vision and colour vision. Also the optical media and the
      fundus have to be examined. If an optical aid is necessary, it should be suitable
      for use in road traffic. In some cases restrictions are necessary, which should
      be noted in the driver's licence. Testing of visual function has to be performed
      with standardised procedures according to the recommendations of DOG and BVA.
      This article will provide readers with an overview of current practices in
      assessing the ability to drive in road traffic and enable them to render an
      accurate professional opinion regarding driver's licences.

PMID- 16586060
TI  - [Recurring asymmetric swelling of the face].

PMID- 16586061
TI  - [Stress, coping, and craniomandibular disorders].
AB  - BACKGROUND: Stress is an etiologic factor of pain-relevant craniomandibular
      disorders (CMD). Interindividual differences in coping with stress and their
      relation to CMD have rarely been examined. PATIENTS AND METHODS: A total of 72
      volunteers (20 men, 52 women) were examined according to the Research Diagnostic
      Criteria for Temporomandibular Disorders. Stress parameters and coping skills
      were assessed by questionnaires. RESULTS: Stress and one coping factor are
      correlated with CMD indices. Linear regression analysis found the Life Event
      Score and cognitive coping by changing appraisals to significantly predict CMD.
      CONCLUSION: Stress and coping skills are independent predictors of CMD.

PMID- 16586063
TI  - Comment to: Hoi-Hansen T, Pedersen-Bjergaard U, Thorsteinsson B (2005) The
      Somogyi phenomenon revisited using continuous glucose monitoring in daily life.
      Diabetologia 48:2437-2438.

PMID- 16586062
TI  - [Central pain processing in chronic low back pain. Evidence for reduced pain
      inhibition].
AB  - INTRODUCTION: A study of patients with low back pain (LBP) had revealed altered
      central pain processing. At an equal pain level LBP patients had considerably
      more neuronal activation in the somatosensory cortices than controls. In a new
      analysis of this dataset, we further investigated the differences in central pain
      processing between LBP patients and controls, looking for possible pathogenic
      mechanisms. METHODS: Central pain processing was studied by functional magnetic
      resonance imaging (fMRI), using equally painful pressure stimuli in a block
      paradigm. In this study, we reanalyzed the fMRI data to statistically compare
      pain-elicited neuronal activation of both groups. RESULTS: Equally painful
      pressure stimulation resulted in a significantly lower increase of regional
      cerebral blood flow (rCBF) in the periaqueductal gray (PAG) of the LBP patients.
      The analysis further revealed a significantly higher increase of rCBF in LBP than
      in HC in the primary and secondary somatosensory cortex and the lateral
      orbitofrontal cortex (LOFK), elicited by these same stimuli. CONCLUSIONS: These
      findings support a dysfunction of the inhibitory systems controlled by the PAG as
      a possible pathogenic mechanism in chronic low back pain.

PMID- 16586064
TI  - PEGylated glucagon-like peptide-1 displays preserved effects on insulin release
      in isolated pancreatic islets and improved biological activity in db/db mice.
AB  - AIMS/HYPOTHESIS: The rapid degradation and clearance of glucagon-like peptide-1
      (GLP-1) by the enzymes dipeptidyl peptidase-IV and neutral endopeptidase 24.11
      are the main impediments to the development of GLP-1 as a potential glucose
      lowering agent. In this study, new enzyme-resistant polyethylene glycol (PEG)
      conjugated GLP-1 analogues were designed and examined for metabolic stability and
      biological potency. MATERIALS AND METHODS: Two mono-PEGylated GLP-1 analogues, N
      terminally modified N-PEG/GLP-1 and Lys-modified Lys-PEG/GLP-1, were prepared.
      Stability was tested in plasma and tissue extracts. In vitro insulin release
      studies were performed using isolated rat pancreatic islets, while in vivo
      glycaemic responses were measured in db/db mice. RESULTS: The half-life of Lys
      PEG/GLP-1 was 40-, 10- and 28-fold longer than that of GLP-1 in plasma, liver and
      kidney homogenates, respectively. Lys-PEG/GLP-1 stimulated insulin secretion in
      the islets in a dose- and glucose-dependent manner, and was as potent as GLP-1.
      In contrast, N-PEG/GLP-1 showed extended metabolic stability but had
      significantly lower biological activity. The administration of Lys-PEG/GLP-1 (9
      nmol/kg i.p.) to non-fasted db/db mice stabilised glycaemia (p<0.001), whereas
      GLP-1 (9 nmol/kg) only caused small changes in glucose level. During OGTT in
      fasted db/db mice, Lys-PEG/GLP-1 administered at 1, 3 and 9 nmol/kg (i.p.)
      reduced the glucose AUC(0-3h) by 48.7+/-9.4, 55.0+/-2.9 and 63.4+/-2.5%,
      respectively, compared with placebo (p<0.01), whereas GLP-1 (9 nmol/kg) lowered
      the glucose level by 39.5+/-12.9% (p<0.01). CONCLUSIONS/INTERPRETATION: This
      study demonstrates that site-specific PEGylated GLP-1 analogues are resistant to
      degradation. The enhanced biological potencies of these analogues highlight their
      potential as new, GLP-1-like glucose-lowering agents.

PMID- 16586066
TI  - Rat bite as a cause of diabetic foot ulcer--a series of eight cases.

PMID- 16586065
TI  - Cardiac overexpression of catalase rescues cardiac contractile dysfunction
      induced by insulin resistance: Role of oxidative stress, protein carbonyl
      formation and insulin sensitivity.
AB  - AIMS/HYPOTHESIS: Insulin resistance leads to oxidative stress and cardiac
      dysfunction. This study examined the impact of catalase on insulin-resistance
      induced cardiac dysfunction, oxidative damage and insulin sensitivity. METHODS:
      Insulin resistance was initiated in FVB and catalase-transgenic mice by 12 weeks
      of sucrose feeding. Contractile and intracellular Ca2+ properties were evaluated
      in cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-90%
      relengthening (TR90), half-width duration (HWD), maximal velocity of
      shortening/relengthening (+/-dL/dt), fura-fluorescence intensity change
      (DeltaFFI) and intracellular Ca2+ clearance rate (tau). Reactive oxygen species
      (ROS) and protein damage were evaluated with dichlorodihydrofluorescein and
      protein carbonyl formation. RESULTS: Sucrose-fed mice displayed
      hyperinsulinaemia, impaired glucose tolerance and normal body weight. Myocytes
      from FVB sucrose-fed mice exhibited depressed PS and +/-dL/dt, prolonged TR90 and
      tau, and reduced DeltaFFI associated with normal TPS and HWD compared with those
      from starch-fed control mice. ROS and protein carbonyl formation were elevated in
      FVB sucrose-fed mice. Insulin sensitivity was reduced, evidenced by impaired
      insulin-stimulated 2-deoxy-D: -[3H]glucose uptake. Western blot analysis
      indicated that sucrose feeding: (1) inhibited insulin-stimulated phosphorylation
      of insulin receptor and Akt; (2) enhanced protein-tyrosine phosphatase 1B (PTP1B)
      expression; and (3) suppressed endothelial nitric oxide synthase (eNOS) and Na+
      Ca2+ exchanger expression without affecting peroxisome proliferator-activated
      receptor gamma (PPARgamma), sarco(endo)plasmic reticulum Ca2+-ATPase isozyme 2a
      and phospholamban. Catalase ablated insulin-resistance-induced mechanical
      dysfunction, ROS production and protein damage, and reduced eNOS, but not insulin
      insensitivity. Catalase itself decreased resting FFI and enhanced expression of
      PTP1B and PPARgamma. CONCLUSIONS/INTERPRETATION: These data indicate that
      catalase rescues insulin-resistance-induced cardiac dysfunction related to ROS
      production and protein oxidation but probably does not improve insulin
      sensitivity.

PMID- 16586067
TI  - Association study of genetic polymorphisms of SLC2A10 gene and type 2 diabetes in
      the Taiwanese population.
AB  - AIMS/HYPOTHESIS: The gene encoding solute carrier family 2, facilitated glucose
      transporter, member 10 (SLC2A10, previously known as glucose transporter 10
      [GLUT10]) is a promising candidate gene for type 2 diabetes since it is highly
      expressed in liver and pancreas and is located on human chromosome region 20q12
      q13.1, a region previously shown to harbour type 2 diabetes susceptibility genes.
      We investigated whether the SLC2A10 gene could be a type 2 diabetes
      susceptibility gene in the Taiwanese population. SUBJECTS AND METHODS: Sequencing
      of SLC2A10 gene from 48 diabetic subjects detected short tandem repeat
      polymorphisms in the promoter region, but did not detect any other sequence
      variants or new single-nucleotide polymorphisms (SNPs) other than those already
      in the SNPper database ( http://snpper.chip.org ) (30 June 2005). RESULTS: Using
      these genetic polymorphisms, we divided the SLC2A10 gene into four distinct
      linkage disequilibrium blocks and performed a case-control association study in a
      group of type 2 diabetes subjects (n = 375) and normoglycaemic individuals
      (n=377). The HapD (A-G-T-C) haplotype in block 3, a rare haplotype, which
      consisted of four SNPs (rs3092412, rs2235491, rs2425904 and rs1059217), was
      modestly associated with type 2 diabetes with a haplotype score of -2.95567 (p =
      0.012 with the haplotype-specific test). CONCLUSIONS/INTERPRETATION: Our results
      suggest that SLC2A10 genetic variations do not appear to be major determinants
      for type 2 diabetes susceptibility in the Taiwanese population.

PMID- 16586068
TI  - The expression of apolipoprotein B epitopes is normal in LDL of diabetic and end
      stage renal disease patients.
AB  - AIMS/HYPOTHESIS: When LDLs are exposed to glucose in vitro, glycation of
      apolipoprotein B100 (apoB) leads to a loss in its affinity for the LDL receptor
      and reproducible alterations in the immunoreactivity of specific apoB epitopes,
      including several epitopes close to the LDL receptor binding site. The aim of
      this work was to determine if similar immunological changes are observed in vivo
      in LDLs of diabetic and end-stage renal disease (ESRD) patients. SUBJECTS,
      MATERIALS AND METHODS: The immunoreactivity of LDLs isolated from 14 diabetic
      patients with normal renal function and 13 patients with ESRD was studied with a
      panel of 25 well-characterised anti-apoB monoclonal antibodies. RESULTS: Although
      diabetic and ESRD LDLs showed evidence of glycation modification, none of the
      changes in the apoB immunoreactivity induced by glucose in vitro was observed in
      vivo, including those for epitopes close to the LDL receptor binding domain.
      CONCLUSIONS/INTERPRETATION: These results suggest that in vivo glycation of LDLs
      is a complex process that is not mimicked by in vitro exposure of LDLs to high
      concentrations of glucose. This questions the clinical significance of the in
      vitro glycation studies used to understand the pathophysiological consequences of
      LDL glycation in diabetes and ESRD.

PMID- 16586069
TI  - Anaemia in diabetes: Is there a rationale to TREAT?
AB  - BACKGROUND: Anaemia is a common finding in patients with diabetes, particularly
      in those with overt nephropathy or renal impairment. In tertiary clinics, at
      least one outpatient in five with diabetes has anaemia, for whom it constitutes a
      significant additional burden. DISCUSSION: Anaemia is associated with an
      increased risk of diabetic complications including nephropathy, retinopathy and
      macrovascular disease. Anaemia may also be significant in determining the outcome
      of heart failure and hypoxia-induced organ damage in diabetes. While several
      factors contribute to the increased prevalence of anaemia in diabetes, the
      failure of the kidney to increase erythropoietin in response to falling
      haemoglobin appears to be the dominant factor. Although there is a clear
      rationale for correcting anaemia in people with diabetes, it remains to be
      established whether this will lead to improved outcomes. Moreover, the balance of
      risks, costs, and benefits remains to be established in patients with diabetes.
      The Trial to Reduce Cardiovascular Events with Aranesp (darbepoetin alpha)
      Therapy (TREAT) is a randomised controlled trial designed to determine the impact
      of anaemia correction on mortality and non-fatal cardiovascular events in
      patients with type 2 diabetes and stage 3-4 nephropathy. CONCLUSION: It is
      anticipated that TREAT will help to define the optimal approach to the management
      of anaemia in diabetes.

PMID- 16586070
TI  - A dose-response study on the estrogenic activity of benzophenone-2 on various
      endpoints in the serum, pituitary and uterus of female rats.
AB  - The tetrahydroxylated biphenyl-ketone 2,2',4,4'-tetrahydroxybenzophenone (BP2),
      one of twelve benzophenone-derived UV-filters, is used in cosmetic products and
      in packaging materials to protect these products from light induced damage.
      Recently published studies showed that BP2 exerts estrogenic activity; thus, it
      is an endocrine active chemical. We present data from a pharmacodynamic dose
      response experiment with five dosages of BP2 applied per gavage to adult
      ovariectomized (ovx) rats for 5 days. Estradiol-valerate (E2) served as a control
      compound. The uterotrophic assay, proposed by the OECD, was modified to have a
      broader view on endocrine activity outside the urogenital tract to prevent that
      undesirable actions in other organs regulated by estrogens are missed. The gene
      expression levels of marker genes of estrogenic action were measured by semi
      quantitative RT-PCR. Metabolic parameters were assessed by determination of the
      serum concentrations of leptin, cholesterol, high- and low-density lipoproteins,
      and triglycerides in the serum. Administration of BP2 at dosages of 10-1,000
      mg/kg bodyweight led to changes of these parameters comparable to the changes in
      the E2 group with 0.6 mg/kg bodyweight. For the observed estrogenic activities of
      BP2, the "no observed adverse effect levels" were determined. Additionally, the
      data were further analyzed using the benchmark approach. If BP2 is
      transcutaneously absorbed in the human, the obtained threshold values would
      suggest refraining from the further use of BP2 as UV-filter in cosmetic products
      although additional toxicological studies should be conducted to clarify possible
      adverse effects.

PMID- 16586071
TI  - Prospective randomized trial of natural interferon-alpha versus natural
      interferon-alpha plus cimetidine in advanced renal cell carcinoma with pulmonary
      metastasis.
AB  - PURPOSE: In a preliminary non-randomized study, combination therapy with natural
      (i.e. non-recombinant) interferon-alpha plus cimetidine obtained a high response
      rate in patients with advanced renal cell carcinoma. We conducted a prospective
      randomized phase III trial to determine whether combination therapy with natural
      interferon-alpha plus cimetidine is superior to natural interferon-alpha alone in
      patients with advanced renal cell carcinoma with pulmonary metastasis. METHODS:
      Patients received 5 million units (MU) natural interferon-alpha per day, five
      times a week, or the 5 MU natural interferon-alpha regimen plus a daily oral
      cimetidine. The primary and secondary end points were the response rate, and the
      time to progression (TTP), respectively. RESULTS: Between April 1998 and March
      2002, 71 patients from 32 institutions were randomly assigned to the 2 treatment
      groups. One patient in each group did not receive any natural interferon-alpha
      whatsoever. Two patients in the natural interferon-alpha alone group stopped
      treatment: on day 9 and on day 10, respectively. In the intent-to-treat analysis,
      1 complete response (CR), 4 partial responses (PRs), 16 no changes (NCs), and 12
      progressive diseases (PDs) were observed among the 36 patients in the interferon
      alpha alone group with a response rate of 13.9%. Of the 35 patients in the
      natural interferon-alpha plus cimetidine group, there were two CRs, 8 PRs, 13
      NCs, and 11 PDs, yielding a response rate of 28.6% (P=0.13). TTP ranged from 9 to
      845 days (median 112 days) in the natural interferon-alpha-alone group, and from
      31 to 1,568 days (median 125 days) in the natural interferon-alpha plus
      cimetidine group (P=0.87). CONCLUSIONS: Combined treatment with natural
      interferon-alpha plus cimetidine for advanced renal cell carcinoma did not result
      in a significant improvement in response rates or TTP compared to natural
      interferon-alpha therapy alone.

PMID- 16586072
TI  - Early diagnosis of SARS: lessons from the Toronto SARS outbreak.
AB  - The clinical presentation of SARS is nonspecific and diagnostic tests do not
      provide accurate results early in the disease course. Initial diagnosis remains
      reliant on clinical assessment. To identify features of the clinical assessment
      that are useful in SARS diagnosis, the exposure status and the prevalence and
      timing of symptoms, signs, laboratory and radiographic findings were determined
      for all adult patients admitted with suspected SARS during the Toronto SARS
      outbreak. Findings were compared between patients with laboratory-confirmed SARS
      and those in whom SARS was excluded by laboratory or public health investigation.
      Of 364 cases, 273 (75%) had confirmed SARS, 30 (8%) were excluded, and 61 (17%)
      remained indeterminate. Among confirmed cases, exposure occurred in the
      healthcare environment (80%) or in the households of affected patients (17%);
      community or travel-related cases were rare (<3%). Fever occurred in 97% of
      patients by the time of admission. Respiratory findings including cough, dyspnea
      and pulmonary infiltrates evolved later and were present in only 59, 37 and 68%
      of patients, respectively, at admission. Direct exposure, fever on the first day
      of illness, and elevated temperature, pulmonary infiltrates, lymphopenia and
      thrombocytopenia at admission were associated with confirmed cases. Rhinorrhea,
      sore throat, and an elevated neutrophil count at admission were associated with
      excluded cases. In the absence of fever or significant exposure, SARS is
      unlikely. Other clinical, laboratory and radiographic findings further raise or
      lower the likelihood of SARS and provide a rational basis for estimating the
      likelihood of SARS and directing initial management.

PMID- 16586073
TI  - Increased nerve growth factor and its receptors in atopic dermatitis: an
      immunohistochemical study.
AB  - Evidence suggests that neurotrophins may regulate certain immune functions and
      inflammation. In the present study, the localization and distribution of nerve
      growth factor (NGF) and its receptors were explored using immunohistochemical
      methods, with the aim of detecting the cause of the neurohyperplasia in early
      lesions of atopic dermatitis (AD). In AD involved skin, strong NGF-immunoreactive
      (IR) cells were observed in the epidermis. In some cases, a huge number of
      infiltrating cells with stronger NGF immunoreactivity was seen mainly in the
      dermal papillae. Some trkA immunoreactivity was observed in the outer membrane of
      cells in the basal and spinal layers of the epidermis. In the papillary dermis, a
      larger number of cells demonstrated strong trkA immunoreactivity. The p75 NGFr-IR
      nerve fibre profiles were increased (900 per mm(2); p<0.001) compared to normal
      [the involved skin also differed from the uninvolved skin (p<0.05)] in the dermal
      papillae. These nerve fibres were larger, coarser and branched, some of them
      terminated at p75 NGFr-IR basal cells, and also revealed a stronger fluorescence
      staining than the controls or the uninvolved skin. In normal healthy volunteers
      and AD uninvolved skin, the NGF immunoreactivity was weak in the basal layer of
      epidermis. Only a few trkA positive cells were seen in the basal layer of the
      epidermis and upper dermis. The IR epidermal basal cells revealed a striking
      patchy arrangement with strong p75 NGFr immunostaining in the peripheral part of
      the cells, and short and thick NGFr-IR nerve fibre profiles appeared as smooth
      endings scattered in the dermis including the cutaneous accessory organs. Using
      NGF and p75 NGFr double staining, both immunoreactivities showed a weak staining
      in the epidermis and dermis in normal and uninvolved skin. In the involved dermis
      of AD, the intensity of p75 NGFr-IR nerves was stronger in areas where there were
      also increased numbers of NGF-IR cells. These findings indicate that NGF and its
      receptors may contribute to the neurohyperplasia of AD.

PMID- 16586074
TI  - Thymol derivatives from hairy roots of Arnica montana.
AB  - Five known thymol derivatives were isolated from roots of Arnica montana
      transformed with Agrobacterium rhizogenes LBA 9402. The compounds were
      characterized by spectral methods. The pattern of thymol derivatives in light
      grown hairy roots was slightly different from that in dark-grown ones. This is
      the first report on the presence of thymol derivatives in hairy roots of the
      plant.

PMID- 16586076
TI  - The fate of the rectal stump after subtotal colectomy for ulcerative colitis.
AB  - OBJECTIVE: To review the outcome of patients who had undergone subtotal colectomy
      for ulcerative colitis with formation of a rectal stump. To specifically look at
      the fate of the rectal stump, whether patients underwent emergency colectomy as
      opposed to urgent or elective resection. PATIENTS AND METHODS: Between January
      1990 and August 2000, a total of 31 patients underwent subtotal colectomy for
      ulcerative colitis. Patients were identified using the computerized coding system
      for the years 1995 to 2000, supplemented by pathology records, discharge letters,
      and operation notes. Postal and telephone surveys were undertaken using a
      standard questionnaire assessing social, physical, sexual, and bowel activities
      of patients. RESULTS: In 28 out of 31 patients, the follow-up was complete.
      Twenty-four of 28 patients (86%) underwent excision of rectal stump. Four
      patients (14%) preferred to undergo excision of rectum only, resulting in a
      permanent ileostomy; 20/28 (71%) had attempted ileal pouch-anal anastomosis, with
      success in 85%. In four patients (14%), the rectal stump remained in situ and was
      associated with a decrease in the quality of life. There were no perioperative
      deaths and morbidity was low for all procedures. CONCLUSION: These data show that
      after subtotal colectomy, the majority of our ulcerative colitis patients undergo
      ileal pouch-anal anastomosis. Patients' satisfaction is high with reasonable
      social and excellent sexual function on quality of life assessment. During its
      retention, the rectal stump causes considerable symptoms. When left in situ, it
      is associated with a decrease in the quality of life.

PMID- 16586075
TI  - Isolation and genetic mapping of a Coffea canephora phenylalanine ammonia-lyase
      gene (CcPAL1) and its involvement in the accumulation of caffeoyl quinic acids.
AB  - Biosynthesis of caffeoylquinic acids occurs via the phenylpropanoid pathway in
      which the phenylalanine ammonia-lyase (PAL) acts as a key-control enzyme. A full
      length cDNA (pF6), corresponding to a PAL gene (CcPAL1), was isolated by
      screening a Coffea canephora fruit cDNA library and its corresponding genomic
      sequence was characterized. Amplification of total DNA from seven Coffea species
      revealed differences in intronic length. This interspecific polymorphism was used
      to locate the gene on a genetic map established for a backcross progeny between
      Coffea pseudozanguebariae and C. dewevrei. The CcPAL1 gene was found on the same
      linkage group, but genetically independent, as a caffeoyl-coenzyme A-O
      methyltransferase gene, another gene intervening in the phenylpropanoid pathway.
      In the same backcross, a lower caffeoylquinic acid content was observed in seeds
      harvested from plants harbouring the C. pseudozanguebariae CcPAL1 allele.
      Involvement of the CcPAL1 allelic form in the differential accumulation of
      caffeoylquinic acids in coffee green beans is then discussed.

PMID- 16586077
TI  - Primary marginal zone B-cell lymphoma of gastrointestinal tract presenting as
      multiple lymphomatoid polyposis.

PMID- 16586078
TI  - Routine use of FDG-PET scans in melanoma patients with positive sentinel node
      biopsy.
AB  - PURPOSE: Positron emission tomography (PET) scanning is an efficient and well
      known diagnostic tool in various malignant disorders. However, the utility of PET
      as a clinical routine screening procedure for the detection of subclinical
      metastases in stage III melanoma patients has not yet been established. METHODS:
      Thirty-three patients with cutaneous malignant melanoma and subclinical lymph
      node metastases diagnosed by sentinel node biopsy (SNB) were submitted to( 18)F
      fluoro-2-deoxy-D: -glucose (FDG) whole-body PET scanning within 100 days after
      SNB and wide local excision. Before PET scanning, patients were screened
      conventionally and found to be without evidence of further dissemination.
      Positive PET scan findings were evaluated by computed tomography scanning,
      magnetic resonance imaging and ultrasonography. Biopsy was performed whenever
      possible. The median follow-up was 15 months (range 6-39 months). RESULTS: Nine
      patients (27%) had a positive PET scan performed after SNB and WLE. On
      verification, four cases (12%) were found to be true positive for melanoma
      metastasis and were thus upgraded from stage III to stage IV. Furthermore, one
      patient (3%) had another primary malignancy (prostate carcinoma), and two (6%)
      were found to have non-malignant lesions. Two PET-positive patients (6%) refused
      further investigations. In one case (3%) the PET scan was false negative. Twenty
      three (69%) PET scans were true negative. CONCLUSION: In a number of stage III
      melanoma patients with positive SNB, postoperative whole-body FDG-PET scanning
      revealed further melanoma dissemination not found by conventional screening
      methods and thus identified these cases as stage IV. Relevant therapy can
      accordingly be instituted earlier on the basis of FDG-PET scanning.

PMID- 16586079
TI  - Comparative assessment of 18F-fluorodeoxyglucose PET and 99mTc-tetrofosmin SPECT
      for the prediction of functional recovery in patients with reperfused acute
      myocardial infarction.
AB  - PURPOSE: Although preserved glucose metabolism is considered to be a marker of
      myocardial viability in the chronic stage, it has not been fully elucidated
      whether this is also true with regard to reperfused acute myocardial infarction
      (AMI). The aim of this study was to compare the diagnostic performance of(99m)Tc
      tetrofosmin SPECT and(18)F-fluorodeoxyglucose (FDG) PET for the prediction of
      functional recovery in reperfused AMI. METHODS: The study population comprised 28
      patients. Both tetrofosmin SPECT and FDG PET were performed in all 28 patients at
      ca. 2 weeks and in 23 at 6 months. The tetrofosmin and FDG findings in infarct
      related segments were compared with the regional wall motion score assessed by
      left ventriculography over 6 months to determine the predictive value for
      functional recovery. RESULTS: Of 120 infarct-related segments, 83 had preserved
      flow (tetrofosmin uptake >/=50%) and 81 had preserved glucose metabolism (FDG
      uptake >/=40%). The sensitivity and specificity of tetrofosmin SPECT for the
      prediction of functional recovery tended to be superior to those of FDG PET
      (90.0% and 72.5% vs 85.0% and 67.5%, respectively). Thirteen segments with
      preserved flow and decreased glucose metabolism demonstrated marked recovery of
      contractile function from 2.5+/-1.0 to 1.4+/-1.4 (p<0.01), with restoration of
      glucose metabolism at 6 months. In contrast, 11 segments with decreased flow and
      preserved glucose metabolism demonstrated incomplete functional improvement from
      3.0+/-0.8 to 2.2+/-1.2. CONCLUSION: In the subacute phase, preserved myocardial
      blood flow is more reliable than glucose metabolism in predicting functional
      recovery in reperfused myocardium.

PMID- 16586080
TI  - Mapping of treatment-induced apoptosis in normal structures: 99mTc-Hynic-rh
      annexin V SPECT and CT image fusion.
AB  - PURPOSE: The purpose of this study was to map treatment-induced (99m)Tc-Hynic-rh
      annexin V uptake in normal tissues using co-registration of SPECT and CT.
      METHODS: Nineteen patients (11 male, 8 female, mean age 57 years) with various
      malignant tumours (12 lymphomas, four non-small cell lung cancers and three head
      and neck squamous cell carcinomas) underwent (99m)Tc-Hynic-rh-annexin V
      scintigraphy and CT before and within 48 h after the start of anticancer therapy.
      SPECT and CT were performed separately, with the patient in a reproducible
      position. Volume-based automated and manual methods were used to match functional
      and anatomical data. SPECT/CT co-registration was used to evaluate treatment
      induced changes in the normal structures. RESULTS: A significant radiation field
      related increase in early post-treatment (99m)Tc-Hynic-rh-annexin V uptake in
      salivary glands and bone marrow was detected in eight of nine patients. Radiation
      field-related increase in bone marrow activity above the baseline value was
      detected in all 13 irradiated patients. A minimal, symmetrical increase in
      activity in the salivary glands was detected after the initial course of platinum
      based chemotherapy, and a diffuse prominent increase in (99m)Tc-Hynic-rh-annexin
      V in the bone marrow was detected in all cases. Precise delineation between the
      tumour and normal tissue tracer accumulation was accomplished in all cases using
      SPECT/CT co-registered volumes, enhanced by the "colourwash" technique.
      CONCLUSION: Mapping of early treatment-related changes in annexin V uptake by
      SPECT/CT co-registration permits accurate evaluation of tracer distribution in
      normal structures and precise delineation from tumour uptake. The associations
      between tracer distribution in the normal tissues and treatment regimen found in
      this study may contribute to the evaluation of dose-effect relations in various
      treatment schedules.

PMID- 16586081
TI  - Elemental composition and source characterization of airborne PM(10) at
      residences with relative proximities to metal-industrial complex.
AB  - OBJECTIVES: Exposure estimates based solely on proximity to air pollution sources
      are not robust and require confirmation. Consequently, the present study was
      designed to scientifically evaluate the atmospheric particulate pollution in
      residences relative to their proximity to a Korean major metal-industrial complex
      (MIC). METHODS: This purpose was achieved by concurrently measuring the
      concentrations and elemental composition of particulate matter with aerodynamic
      diameters equal to or less than 10 microm (PM(10)) and characterizing the PM(10
      )source types in industrial ambient air from MIC and residential ambient air with
      relative proximities to MIC. Trace metals were analyzed using an inductively
      coupled plasma-atomic emission spectroscopy (ICP-AES). The elemental composition
      data were employed to calculate enrichment factors and statistically analyzed
      using a principal component analysis (PCA) to characterize the PM(10) source
      types. The source contributions were quantitatively analyzed using an absolute
      PCA (APCA). RESULTS: The most enriched elements for which a significant
      anthropogenic origin can be suggested were Cd, Cu, Pb, Sb, Tl, and Zn. For PCA,
      four or five factors with eigenvalues greater than unity were obtained for each
      sampling site, and those having high loadings with the same variables represented
      similar source types. The APCA result yielded significant regression
      coefficients, explaining 74-85% of the variability in the PM(10), which depends
      on the sampling site. The industrial mean values exceeded the Korean year/70
      microg/m(3) standard for PM(10), whereas the residential mean values did not.
      However, the maximum residential values did exceed or were close to the Korean
      PM(10 )year standard. For individual elements, the ambient concentrations ranged
      widely from values in the order of a few ng/m(3 )to thousands of ng/m(3). The
      residential mean mass concentrations in the PM(10) measured in the present study
      were higher than or similar to those reported in earlier studies. CONCLUSIONS:
      The present study confirmed that residents in neighborhoods near the MIC are
      exposed to elevated particulate and metal levels compared to residents living
      further away from such a source, thereby supporting that proximity to air
      pollution sources can be employed to indicate environmental exposure.

PMID- 16586082
TI  - The determinants of prevalence of health complaints among young competitive
      swimmers.
AB  - OBJECTIVES: Chloramines, which are produced by the reaction of chlorine with the
      organic matter present in indoor pools, are potential airway irritants in
      swimmers. The objective of this study was to compare the prevalence of health
      complaints of young swimmers and young indoor soccer players and to evaluate the
      relationship between chloramine concentrations and the athletes' health
      complaints. METHODS: Health complaints were first (Part 1) documented by
      questionnaire in 305 competitive swimmers and 499 indoor soccer players of the
      Quebec City region (Canada). Then, (Part 2) health complaints were documented
      during five training sessions in 72 competitive swimmers in comparison to 73
      soccer players. The chloramines in the swimming pool air and water were measured
      as well as the peak expiratory flow (PEF) before and after the training session.
      RESULTS: In Part 1, the swimmers reported more lower (adjusted OR: 1.5; IC95%=
      1.0-2.2) and upper respiratory symptoms (adjusted OR: 3.7; IC95%= 2.4-5.8). In
      Part 2, the swimmers experienced more frequent lower (adjusted OR: 3.5; IC95%=
      2.0-6.0) and upper respiratory symptoms (adjusted OR: 3.1; IC95%= 1.8-5.4).
      Overall, swimmers exposed to the highest levels of chloramines in the air and
      water had more respiratory complaints. CONCLUSIONS: Swimmers exposed to
      chlorination by-products in both the water and air of indoor swimming pools
      experience frequent respiratory symptoms that could potentially be reduced by
      limiting exposure to these products.

PMID- 16586085
TI  - Orientation response of haematophagous bugs to CO2: the effect of the temporal
      structure of the stimulus.
AB  - Carbon dioxide is generally recognized as an important cue used by haematophagous
      insects to locate a food source. When the mammalian hosts of these insects
      breathe, they normally emanate considerable amounts of CO2 at discrete intervals,
      i.e. with each exhalation. In this work, we analysed the effect of temporally
      pulsing CO2 on the host-seeking behaviour of Triatoma infestans. We investigated
      the ability of T. infestans to follow continuous and intermittent air pulses of
      0.25, 0.5 and 1 Hz that included different concentrations of CO2. We found that
      insects were attracted to pulsed airstreams of 0.25 and 0.5 Hz transporting 400
      ppm of CO2 above the ambient levels and to continuous streams added with the same
      amount of CO2. On the other hand, insects walked away from streams pulsed at
      rates of 1 Hz regardless of the amount of CO2 they bear. The walking trajectories
      displayed by bugs to attractive CO2-pulsed streams were as rectilinear and
      accurate as those to CO2-continuous streams. Our results are discussed in the
      frame of the interaction between olfactory and mechanoreceptive inputs as
      affecting the behavioural response of bugs.

PMID- 16586084
TI  - Mechanical reconfiguration mediates swallowing and rejection in Aplysia
      californica.
AB  - Muscular hydrostats, such as tongues, trunks or tentacles, have fewer constraints
      on their degrees of freedom than musculoskeletal systems, so changes in a
      structure's shape may alter the positions and lengths of other components (i.e.,
      induce mechanical reconfiguration). We studied mechanical reconfiguration during
      rejection and swallowing in the marine mollusk Aplysia californica. During
      rejection, inedible material is pushed out of an animal's buccal cavity. The
      grasper (radula/odontophore) closes on inedible material, and then a posterior
      muscle, I2, pushes the grasper toward the jaws (protracts it). After the material
      is released, an anterior muscle complex (the I1/I3/jaw complex) pushes the
      grasper toward the esophagus (retracts it). During swallowing, the grasper is
      protracted open, and then retracts closed, pulling in food. Grasper closure
      changes its shape. Magnetic resonance images show that grasper closure lengthens
      I2. A kinetic model quantified the changes in the ability of I2 and I1/I3 to
      exert force as grasper shape changed. Grasper closure increases I2's ability to
      protract during rejection, and increases I1/I3's ability to retract during
      swallowing. Motor neurons controlling radular closure may therefore affect the
      behavioral outputs of I2's and I1/I3's motor neurons. Thus, motor neurons may
      modulate the outputs of other motor neurons through mechanical reconfiguration.

PMID- 16586086
TI  - Enhanced acquisition of cocaine self-administration by increasing percentages of
      C57BL/6J genes in mice with a nonpreferring outbred background.
AB  - RATIONALE: Individual differences in the propensity to acquire drug self
      administration may have a substantial genetic basis. OBJECTIVES: To study the
      genetic contribution to cocaine self-administration by comparing hybrids of
      cocaine preferring (C57BL/6J) and nonpreferring (ICR) mice. METHODS: ICR and
      C57BL/6J parental strains were compared to hybrids with 75% ICR:25% C57BL/6J, 50%
      ICR:50% C57BL/6J, and 25% ICR:75% C57BL/6J genetic backgrounds for acquisition of
      sucrose pellet and intravenous cocaine self-administration in 1-h test sessions.
      Mice that acquired cocaine self-administration were subsequently tested in a
      between-session self-administration dose-response procedure. RESULTS: Increasing
      presence of C57BL/6J genes increased the percentage of mice that acquired sucrose
      pellet self-administration in the first test session. In lever-trained mice, only
      19% of ICR mice met acquisition criteria for cocaine self-administration after 15
      sessions, whereas 76% of C57BL/6J mice met acquisition criteria, although both
      strains initially sampled a similar number of cocaine injections. Increasing the
      percentage of C57BL/6J genes in the nonpreferring ICR background to 50 and 75%
      led to increasing percentages of mice that met acquisition criteria to 31 and
      52%, respectively. In mice that acquired self-administration, only mice with 75%
      C57BL/6J genes showed a typical inverted U-shaped self-administration dose
      response curve, whereas the curve was flat across doses for mice with < or = 50
      and 100% C57BL/6J genes. CONCLUSIONS: The findings are consistent with a
      genetically based dose-dependent enhancement of cocaine reinforcement by C57BL/6J
      genes. These results suggest that heritable traits impart a substantial genetic
      load that facilitates the propensity for cocaine addiction among individuals in
      outbred populations.

PMID- 16586083
TI  - Cardiovascular risk with cyclooxygenase inhibitors: general problem with
      substance specific differences?
AB  - Randomised clinical trials and observational studies have shown an increased risk
      of myocardial infarction, stroke, hypertension and heart failure during treatment
      with cyclooxygenase inhibitors. Adverse cardiovascular effects occurred mainly,
      but not exclusively, in patients with concomitant risk factors. Cyclooxygenase
      inhibitors cause complex changes in renal, vascular and cardiac prostanoid
      profiles thereby increasing vascular resistance and fluid retention. The
      incidence of cardiovascular adverse events tends to increase with the daily dose
      and total exposure time. A comparison of individual selective and unselective
      cyclooxygenase inhibitors suggests substance-specific differences, which may
      depend on differences in pharmacokinetic parameters or inhibitory potency and may
      be contributed by prostaglandin-independent effects. Diagnostic markers such as N
      terminal pro brain natriuretic peptide (NT-proBNP) or high-sensitive C-reactive
      protein might help in the early identification of patients at risk, thus avoiding
      the occurrence of serious cardiovascular toxicity.

PMID- 16586087
TI  - Impairment of contrast sensitivity in long-term lorazepam users.
AB  - RATIONALE: Oculomotor balance and contrast sensitivity are known to be impaired
      after an intake of a single dose of lorazepam. To the best of our knowledge,
      these effects have not been explored in long-term users of lorazepam, despite the
      potential importance of such deficits in everyday life. OBJECTIVE: We tested the
      ophthalmological effects and contrast sensitivity for static stimuli in long-term
      lorazepam users. MATERIALS AND METHODS: There were 15 lorazepam users and 15 sex
      , age- and education level-matched control subjects tested, using a simple blind
      procedure. RESULTS: The ophthalmological effects were scarce, with a discrete
      exophoria. Visual acuity was preserved. Contrast sensitivity, however, was more
      markedly impaired, consistent with the effects of an acute dose of lorazepam. The
      effects were not correlated with anxiety or sedation. CONCLUSIONS: The results
      are discussed in terms of their possible impact on everyday life. As visual
      acuity does not allow the detection of the impairments that are observed in the
      present study, it is suggested that a more systematic exploration of contrast
      sensitivity be carried out in long-term users of benzodiazepines.

PMID- 16586088
TI  - Periadolescent and adult rats respond differently in tests measuring the
      rewarding and aversive effects of nicotine.
AB  - RATIONALE: Initiation of tobacco use typically begins during adolescence, and the
      nature of these first experiences with nicotine may affect the probability of
      continued use. In rodents, a number of studies suggest that periadolescents are
      more responsive to the rewarding effects of nicotine compared to adults.
      OBJECTIVES: This study was designed to determine if there are age differences in
      the rewarding and aversive effects of nicotine by using the conditioned place
      preference (CPP) and conditioned taste avoidance (CTA) paradigms, respectively.
      We also examined age differences in locomotor responses to nicotine. METHODS: In
      the CPP paradigm, male periadolescent and adult Wistar rats received nicotine
      (0.2, 0.4, or 0.8 mg/kg, s.c.) or vehicle prior to place conditioning trials. In
      the CTA paradigm, in separate groups of rats, periadolescents and adults were
      exposed to a 0.1% saccharin solution, followed by the administration of nicotine
      (0.2, 0.4, or 0.8 mg/kg, s.c.) or vehicle. Four saccharin-nicotine pairings were
      followed by a preference test and three extinction sessions. RESULTS: In the CPP
      paradigm, nicotine produced a dose-dependent place preference in periadolescent,
      but not in adult, rats. In the CTA paradigm, adult rats expressed a dose
      dependent avoidance of saccharin after pairings with nicotine, whereas
      periadolescents were resistant to CTA formation. With regard to locomotor
      activity, adults and periadolescents showed comparable locomotor responses to
      nicotine. CONCLUSIONS: These results suggest that periadolescent rats find
      nicotine more rewarding and less aversive, compared to adult rats. This shift in
      the balance between the rewarding and aversive effects of nicotine may make
      adolescents more susceptible to continued nicotine use.

PMID- 16586089
TI  - Antidepressant-like effects of PDE4 inhibitors mediated by the high-affinity
      rolipram binding state (HARBS) of the phosphodiesterase-4 enzyme (PDE4) in rats.
AB  - RATIONALE: Phosphodiesterase-4 (PDE4) has two conformation states based on
      rolipram binding, the high-affinity rolipram binding state (HARBS) and the low
      affinity rolipram binding state (LARBS); their functions remain to be fully
      explained. OBJECTIVE: Experiments were carried out to determine the roles of the
      HARBS and LARBS in the mediation of antidepressant-like effects on behavior.
      MATERIALS AND METHODS: Two animal models sensitive to antidepressant drugs, the
      forced-swim test (FST), and the differential-reinforcement-of-low-rate (DRL) 72-s
      operant schedule, were used to examine the antidepressant-like effects of
      rolipram, CDP840, and piclamilast, PDE4 inhibitors that interact differentially
      with the HARBS and LARBS, and MEM1018 and MEM1091, two novel PDE4 inhibitors.
      Drug discrimination vs rolipram and rolipram competition binding assays also were
      carried out. RESULTS: In the FST, rolipram and piclamilast, both at 0.1 mg/kg,
      produced an antidepressant-like effect, i.e., reduced immobility and increased
      swimming, whereas, 1 mg/kg of CDP840 or 0.5 mg/kg of MEM1018 or MEM1091 was
      required to produce a similar effect. Consistent with this, only rolipram and
      piclamilast produced antidepressant-like effects in rats under the DRL schedule
      of reinforcement, as evidenced by decreased response rates and increased
      reinforcement rates. In addition, in rats trained to discriminate rolipram from
      its vehicle, only rolipram and piclamilast substituted. Finally, [(3)H]rolipram
      and [(3)H]piclamilast binding analysis revealed that CDP840 and the two novel
      PDE4 inhibitors MEM1018 and MEM1091 exhibited a lower affinity for the HARBS than
      did rolipram. CONCLUSION: These results suggest that the HARBS of PDE4 is the
      primary conformation important for antidepressant-like effects on behavior.

PMID- 16586090
TI  - Neonatal neurosteroid administration results in development-specific alterations
      in prepulse inhibition and locomotor activity: neurosteroids alter prepulse
      inhibition and locomotor activity.
AB  - RATIONALE: Early life exposure to stress and to GABAA receptor modulators have
      well-defined and persistent behavioral effects. A single neonatal injection of
      the GABAergic neurosteroid allopregnanolone (3alpha-hydroxy,5alpha-pregnane-20
      one, 10 mg/kg, i.p.) alters the localization of prefrontal cortex (PFC)
      interneurons in adulthood. Such displacement could result in disinhibited
      behavior associated with impaired development of the mesocortical dopamine
      system. OBJECTIVES: To determine if there is a critical window in which
      allopregnanolone levels may impact the development and mature function of the
      mesocorticolimbic circuitry. METHODS: Behavioral measures, including prepulse
      inhibition (PPI) and total locomotor activity, after amphetamine exposure were
      assessed at postnatal day 20 (P20) (prepuberty), P40 (puberty), P60
      (postpuberty), and P80 (adulthood) in animals previously exposed to
      allopregnanolone (10 mg/kg) on P2 and P5. PFC tyrosine hydroxylase
      immunoreactivity was stereologically measured. RESULTS: P2 administration of
      allopregnanolone resulted in an increased locomotor response to amphetamine (14,
      28% on P20 and P80, respectively) and reduced PPI (28, 22% on P20 and P80,
      respectively) at P20 and P80, whereas allopregnanolone administration on P5
      increased locomotor response to amphetamine (20%) and reduced PPI (37%) at P80.
      Clozapine (7.5 mg/kg) pretreatment reversed the PPI deficit in P2-exposed
      animals. The total length of tyrosine hydroxylase immunopositive fibers in PFC
      was not altered by neonatal neurosteroid exposure, but more fibers were located
      in layers V/VI vs I-III. CONCLUSIONS: Altering neonatal allopregnanolone levels
      disrupts PFC-dependent behavior, indicating that allopregnanolone might be
      important for normal PFC circuitry development. The temporal exposure differences
      (P2 vs P5) and ontological-dependent effects (P20 and P80, but not P40 or P60)
      suggest critical windows of vulnerability to neurosteroid insult across
      development.

PMID- 16586091
TI  - Postmortem cytokine levels and severity of traumatic injuries.
AB  - The relationship between postmortem serum cytokine levels and severity of
      traumatic injuries was studied. The postmortem serum levels of interleukin-6 (IL
      6) and interleukin-8 (IL-8) of 131 victims who died from traumatic injury were
      measured by an enzyme-linked immunosorbent assay method and compared with scores
      of total abbreviated injury scale (total AIS) and injury severity score (ISS)
      calculated from detailed autopsy reports. A significant positive correlation was
      observed between IL-6 and total AIS (rs=0.4508, p<0.0001), between IL-6 and ISS
      (rs=0.3337, p<0.0001), between IL-8 and total AIS (rs=0.6593, p<0.0001), and
      between IL-8 and ISS (rs=0.5305, p<0.0001). The significant correlation between
      cytokine levels and anatomical traumatic severity indicated that the cytokine
      levels are useful objective indexes of traumatic severity. In addition, the total
      AIS is a suitable marker to evaluate traumatic severity as the coefficient of
      correlation between the cytokine levels and the total AIS was higher than that
      for the ISS values.

PMID- 16586092
TI  - Contribution of I Ks to ventricular repolarization in canine myocytes.
AB  - The role of the slow delayed rectifier K(+) current (I (Ks)) in cardiac
      repolarization seems to be largely influenced by the experimental conditions
      including the species and tissue studied. The aim of this study was to determine
      the contribution of I (Ks) to repolarization in canine ventricular myocytes by
      measuring the frequency dependent action potential lengthening effect of 10
      microM chromanol 293B using sharp microelectrodes. Pretreatment with
      isoproterenol (2 nM), E-4031 (1 microM), and injection of inward current pulses
      were applied to modify action potential configuration. Chromanol alone caused
      moderate but statistically significant lengthening of action potentials at cycle
      lengths longer than 500 ms. The lengthening effect of chromanol, which was
      strongly enhanced in the presence of either isoproterenol or E-4031, was
      proportional to the amplitude of plateau, whereas poor correlation was found with
      action potential duration. Similar results were obtained when action potential
      configuration was modified by injection of depolarizing current pulses. Computer
      simulations revealed that activation of I (Ks) is a sharp function of the plateau
      amplitude within the physiological range, while elongation of repolarization may
      enhance I (Ks) only when it is excessive. It was concluded that the effect of I
      (Ks) on ventricular repolarization critically depends on the level of action
      potential plateau; however, other factors, like action potential duration, cycle
      length, or suppression of other K(+) currents can also influence its
      contribution.

PMID- 16586094
TI  - Effects of insulin-like growth factor-I on the maturation of metabolism in
      neonatal rat cardiomyocytes.
AB  - Myocardial metabolism shifts during the perinatal period from predominant
      utilization of glucose towards oxidation of fatty acids. Expression of enzymes of
      the fatty acid oxidation (FAO) pathway is under the control of the nuclear
      receptor/transcription factor peroxisome proliferator-activated receptor alpha
      (PPARalpha). Insulin-like Growth Factor-I (IGF-I) plays an important role in the
      post-natal growth and differentiation of the heart. We determined the influence
      of IGF-I on the maturation of myocardial metabolism. In neonatal rat cardiac
      myocytes, expression of the FAO enzymes MCAD and M-CPT I was induced by treatment
      with the specific PPARalpha agonist WY-14643. Concomitant treatment with IGF-I
      enhanced the expression of both FAO enzymes. By comparison, treatment with FGF-2,
      which is required for myocyte differentiation of cardiac precursors, did not
      increase WY-14643-induced expression of FAO enzymes. Despite stimulation of FAO
      enzyme expression, IGF-I did not further enhance WY-14643-stimulated palmitate
      oxidation. In contrast, IGF-I relieved WY-14643-mediated inhibition of glucose
      uptake and promoted storage of fatty acids into cellular neutral lipids. In
      conclusion, IGF-I promotes a more mature pattern of FAO gene expression but,
      because of insulin-like metabolic effects, does not concomitantly enhance
      oxidation of fatty acids.

PMID- 16586095
TI  - Acute and prolonged effects of TNF-alpha on the expression and secretion of
      inflammation-related adipokines by human adipocytes differentiated in culture.
AB  - The pro-inflammatory cytokine TNF-alpha has multiple effects on adipocyte
      function, including the production of adipokines. In this paper, we have examined
      the acute vs prolonged effects of TNF-alpha on the expression and secretion of
      key inflammation-related adipokines by human adipocytes. Adipocytes
      differentiated in culture were treated with TNF-alpha for 1-24 h, mRNA
      quantitated by real-time polymerase chain reaction (PCR) and secreted adipokines
      by ELISA. Treatment of adipocytes with TNF-alpha for up to 24 h had little effect
      on MIF, MT-2 and PAI-1 mRNA levels. TNF-alpha decreased adiponectin, adipsin,
      haptoglobin and leptin mRNA levels by 24 h, but adiponectin and haptoglobin mRNA
      was initially increased. In contrast, TNF-alpha induced rapid and substantial
      increases in expression of the genes encoding IL-6, MCP-1, NGF and TNF-alpha
      itself; IL-6 and TNF-alpha mRNA levels peaked at 2 h with 75-fold and 600-fold
      increases, respectively. The elevated MCP-1, NGF and VEGF mRNA levels were
      sustained between 4 and 24 h. The adipokine secretion pattern largely paralleled
      cellular mRNA levels; IL-6 (transiently), MCP-1, NGF and VEGF release were
      stimulated by TNF-alpha, with an accelerating rate of MCP-1 secretion over 24 h.
      TNF-alpha has rapid and substantial effects on the synthesis of key inflammation
      related adipokines in human adipocytes, with highly gene-specific responses.

PMID- 16586093
TI  - P2 receptors: intracellular signaling.
AB  - P2 receptors for extracellular nucleotides are divided into two categories: the
      ion channel receptors (P2X) and the G-protein-coupled receptors (P2Y). For the
      P2X receptors, signal transduction appears to be relatively simple. Upon
      activation by extracellular ATP, a channel comprised of P2X receptor subunits
      opens and allows cations to move across the plasma membrane, resulting in changes
      in the electrical potential of the cell that, in turn, propagates a signal. This
      regulated flux of ions across the plasma membrane has important signaling
      functions, especially in impulse propagation in the nervous system and in muscle
      contractility. In addition, P2X receptor activation causes the accumulation of
      calcium ions in the cytoplasm, which is responsible for activating numerous
      signaling molecules. For the P2Y receptors, signal transduction is more complex.
      Intracellular signaling cascades are the main routes of communication between G
      protein-coupled receptors and regulatory targets within the cell. These signaling
      cascades operate mainly by the sequential activation or deactivation of
      heterotrimeric and monomeric G proteins, phospholipases, protein kinases,
      adenylyl and guanylyl cyclases, and phosphodiesterases that regulate many
      cellular processes, including proliferation, differentiation, apoptosis,
      metabolism, secretion, and cell migration. In addition, there are numerous ion
      channels, cell adhesion molecules and receptor tyrosine kinases that are
      modulated by P2Y receptors and operate to transmit an extracellular signal to an
      intracellular response. These intracellular signaling pathways and their
      regulation by P2 receptors are discussed in this review.

PMID- 16586097
TI  - The ABCA subfamily--gene and protein structures, functions and associated
      hereditary diseases.
AB  - To date, 12 members of the human ABCA subfamily are identified. They share a high
      degree of sequence conservation and have been mostly related with lipid
      trafficking in a wide range of body locations. Mutations in some of these genes
      have been described to cause severe hereditary diseases related with lipid
      transport, such as fatal surfactant deficiency or harlequin ichthyosis. In
      addition, most of them are hypothesized to participate in the subcellular
      sequestration of drugs, thereby being responsible for the resistance of several
      carcinoma cell lines against drug treatment. The objective of this review is to
      summarize the literature for this subfamily of ABC transporter proteins,
      excluding ABCA1 and ABCA4, which will be discussed in other chapters of this
      issue.

PMID- 16586096
TI  - Multidrug resistance-associated proteins 3, 4, and 5.
AB  - We summarize in this paper the recently published results on multidrug resistance
      associated proteins 3, 4, and 5 (MRPs 3-5). MRP3 can transport organic compounds
      conjugated to glutathione, sulfate, or glucuronate, such as estradiol-17beta
      glucuronide, bilirubin-glucuronides, and etoposide-glucuronide, and also bile
      salts and methotrexate. Studies in knockout mice have shown that Mrp3 contributes
      to the transport of morphine-3-glucuronide and acetaminophen-glucuronide from the
      liver into blood. There is no evidence for a major role of MRP3 in bile salt
      metabolism, at least in mice. The function of MRP3 in other tissues, notably the
      gut and the adrenal cortex, remains to be defined. MRP4 and MRP5 have attracted
      attention by their ability to transport cyclic nucleotides and many nucleotide
      analogs. The initial reports that MRP4 and 5 can transport cGMP with microM
      affinity have not been confirmed in recent work and the physiological importance
      of cyclic nucleotide transport by MRP4 and 5 remains to be determined.
      Transfected cells containing high concentrations of MRP4 and 5 are moderately
      resistant to base, nucleoside, and nucleotide analogs. The affinity of both
      transporters for nucleotide analogs is low (K (m) around 1 mM) and there is no
      evidence that the transport of these compounds results in resistance in vivo. The
      physiological function of MRP4 and 5 remains to be found.

PMID- 16586100
TI  - The chemokine SDF-1 regulates blastema formation during zebrafish fin
      regeneration.
AB  - The work presented in this study focuses on blastema formation in epimorphic
      regeneration. We describe the expression pattern of Sdf1a and Sdf1b (the
      chemokines stromal-cell-derived factor-1a and 1b) and their two receptors Cxcr4a
      and Cxcr4b during zebrafish fin regeneration. We demonstrate that Sdf1a/Cxcr4a
      plays a critical role in fin regeneration and more precisely in epidermal cell
      proliferation, an important process for blastema formation. In mammals, a single
      cxcr4 gene is involved both in chemotaxis and cell proliferation and survival; we
      discuss in this study a possible functional division of the two cxcr4 zebrafish
      genes.

PMID- 16586098
TI  - The Na+/H+ exchanger NHE1 in stress-induced signal transduction: implications for
      cell proliferation and cell death.
AB  - The ubiquitous plasma membrane Na+/H+ exchanger NHE1 is highly conserved across
      vertebrate species and is extensively characterized as a major membrane transport
      mechanism in the regulation of cellular pH and volume. In recent years, the
      understanding of the role of NHE1 in regulating cell function has expanded from
      one of a household protein involved in ion homeostasis to that of a multifaceted
      regulator and/or modulator of a wide variety of cell functions. NHE1 plays
      pivotal roles in response to a number of important physiological stress
      conditions which, in addition to cell shrinkage and acidification, include
      hypoxia and mechanical stimuli, such as cell stretch. It has recently become
      apparent that NHE1-mediated modulation of, e.g., cell migration, morphology,
      proliferation, and death results not only from NHE1-mediated changes in pHi, cell
      volume, and/or [Na+]i, but also from direct protein-protein interactions with,
      e.g., ezrin/radixin/moesin (ERM) proteins and regulation of cellular signaling
      events, including the activity of mitogen-activated protein kinases (MAPKs) and
      Akt/protein kinase B (PKB). The aim of this review is to present and discuss new
      findings implicating NHE1 activation as a central signaling event activated by
      stress conditions and modulating cell proliferation and death. The
      pathophysiological importance of NHE1 in modulating the balance between cell
      proliferation and cell death in cancer and in ischemia/severe hypoxia will also
      be briefly addressed.

PMID- 16586099
TI  - Phenotype analysis of mice deficient in the peptide transporter PEPT2 in response
      to alterations in dietary protein intake.
AB  - The peptide transporter PEPT2 mediates cellular uptake of di- and tripeptides
      driven by an inwardly directed electrochemical proton gradient. In mammals PEPT2
      is found in a variety of organs such as kidney, lung, brain, enteric nervous
      system, and mammary gland. Highest expression levels are observed in renal
      proximal tubules where PEPT2 contributes to reabsorption of filtered di- and
      tripeptides. To assess the physiological importance of the transporter in overall
      metabolism, we have generated a Pept2-/- mouse line that lacks a functional PEPT2
      protein. Here we present data on body weight, organ weights, and blood pressure.
      Mice were then fed diets containing either 10, 20, or 30% (w/w) protein, and food
      and water intake rates as well as plasma and urine parameters were determined. In
      spite of PEPT2 expression in a variety of tissues, only subtle phenotypic changes
      were observed. Male PEPT2 null mice displayed lower bodyweight and lower relative
      heart weight, whereas, relative kidney weight was lower in female Pept2-/- mice.
      No differences were found in blood pressure. When fed diets with different
      protein contents, Pept2-/- mice adapted food intake to dietary protein content
      with higher consumption rates on low protein and reduced food intake rates on the
      high protein diet.

PMID- 16586101
TI  - Using dual-process theory and analogical transfer to explain facilitation on a
      hypothetico-deductive reasoning task.
AB  - Using the analogical transfer paradigm, the present study investigated the
      competing explanations of Girotto and Legrenzi (Psychological Research 51: 129
      135, 1993) and Griggs, Platt, Newstead, and Jackson (Thinking and Reasoning 4: 1
      14, 1998) for facilitation on the SARS version of the THOG problem, a hypothetico
      deductive reasoning task. Girotto and Legrenzi argue that facilitation is based
      on logical analysis of the task [System 2 reasoning in Evans's (Trends in
      Cognitive Sciences 7: 454-459, 2003) dual-process account of reasoning] while
      Griggs et al. maintain that facilitation is due to an attentional heuristic
      produced by the wording of the problem (System 1 reasoning). If Girotto and
      Legrenzi are correct, then System 2 reasoning, which is volitional and
      responsible for deductive reasoning, should be elicited, and participants should
      comprehend the solution principle of the THOG task and exhibit analogical
      transfer. However, if Griggs et al. are correct, then System 1 reasoning, which
      is responsible for heuristic problem solving strategies such as an attentional
      heuristic, should occur, and participants should not abstract the solution
      principle and transfer should not occur. Significant facilitation (68 and 82%
      correct) was only observed for the two SARS source problems, but significant
      analogical transfer did not occur. This lack of transfer suggests that System 1
      reasoning was responsible for the facilitation observed in the SARS problem,
      supporting Griggs et al.'s attentional heuristic explanation. The present results
      also underscore the explanatory value of using analogical transfer rather than
      facilitation as the criterion for problem understanding.

PMID- 16586102
TI  - Analysis of a processing system for proteases using yeast cell surface
      engineering: conversion of precursor of proteinase A to active proteinase A.
AB  - The display of a protease, carboxypeptidase Y (CPY) or procarboxypeptidase Y
      (proCPY), which is the vacuolar protease, on the yeast-cell surface was
      successfully performed using yeast-cell-surface engineering for the first time.
      Through that we could confirm the processing of vacuolar proteases containing
      proteinase A (PrA) and proteinase B (PrB) which are related to the maturation of
      proCPY, using a novel cell-surface engineering technique. Various protease
      knockout strains of Saccharomyces cerevisiae with the CPY-displaying system were
      constructed to evaluate the operation of the activation process of CPY. The
      display of CPY (CPY-agg, which is a fusion protein of CPY with C-terminal half of
      alpha-agglutinin) on the cell surface was confirmed by immunofluorescence
      staining. The activity of the CPY-agg was determined after the conversion of
      proCPY to active CPY by treatment of whole cells with proteinase K. In the proCPY
      displaying CPY-knockout strain and PrB-knockout strain, CPY was displayed as an
      active (mature) form, but in the proCPY-displaying PrA-knockout strain, CPY was
      present as an inactive form (proCPY). These facts indicate that PrA had been
      already activated before its transport to the vacuole and that active mature PrA
      might convert proCPY to CPY before the transport of proCPY to the vacuole. From
      these results, it was suggested that by using the yeast-cell-surface engineering
      at the location of the initial step, the autocatalytic activation from proPrA to
      PrA might occur before the vacuolar branch separates from the main secretory
      pathway.

PMID- 16586103
TI  - Biocatalytic production of enantiopure cyclohexane-trans-1,2-diol using
      extracellular lipases from Bacillus subtilis.
AB  - Two extracellular lipases from Bacillus subtilis, B. subtilis lipase A and lipase
      B, have been expressed in the heterologous host Escherichia coli, biochemically
      characterized and used for the kinetic resolution of (rac)-trans-1,2
      diacetoxycyclohexane. Both enzymes were selectively acting on the (R,R)
      enantiomer of the racemic substrate, highly specifically hydrolyzing only one of
      the two ester groups present, thus allowing the preparation of enantiopure (R,R)-
      and (S,S)-cyclohexane-trans-1,2-diol. The reaction conditions for the use of
      purified enzyme and crude cell lyophilizate were optimized and reactions in batch
      and repetitive batch modes were carried out on a preparative scale to yield
      enantiopure product (>99% enantiomeric excess).

PMID- 16586104
TI  - Molecular plant breeding: achievements in green biotechnology and future
      perspectives.
AB  - Since one decade ago, transgenic crop plants are globally grown; in 2004, it was
      estimated to cover a total of 81 Mio ha in 17 countries. At present, four plant
      species (soybean, maize, cotton and rapeseed) dominate with two traits (herbicide
      tolerance and insect resistance). The traits on which research concentrates and
      the constructs which might come next onto the market are outlined. The procedure
      on how to clone such genes of interest, e.g. via map-based cloning, and some
      other helpful approaches of green biotechnology, like high throughput techniques
      and functional markers, are summarised, and a rough calculation about the market
      value of transgenic crops in US dollars is quoted.

PMID- 16586105
TI  - Growth of Pleurotus ostreatus on wheat straw and wheat-grain-based media:
      Biochemical aspects and preparation of mushroom inoculum.
AB  - Mycelial growth, intracellular activity of proteases, laccases and beta-1,3
      glucanases, and cytoplasmic protein were evaluated in the vegetative phase of
      Pleurotus ostreatus grown on wheat straw and in wheat-grain-based media in Petri
      dishes and in bottles. The productivity of the wheat straw and wheat-grain-based
      spawn in cylindrical polyethylene bags containing 5 kg of chopped straw was also
      determined. We observed high activity of proteases and high content of
      intracellular protein in cultures grown on wheat straw. This suggests that the
      proteases are not secreted into the medium and that the protein is an important
      cellular reserve. On the contrary, cultures grown on wheat straw secreted
      laccases into the medium, which could be induced by this substrate. P. ostreatus
      grown on media prepared with a combination of wheat straw and wheat grain showed
      a high radial growth rate in Petri dishes and a high level of mycelial growth in
      bottles. The productivities of wheat straw and wheat-grain-based spawn were
      similar. Our results show that cheaper and more productive mushroom spawn can be
      prepared by developing the mycelium on wheat straw and wheat-grain-based
      substrates.

PMID- 16586106
TI  - PprA: A protein implicated in radioresistance of Deinococcus radiodurans
      stimulates catalase activity in Escherichia coli.
AB  - PprA: a pleiotropic protein promoting DNA repair, role in radiation resistance of
      Deinococcus radiodurans was demonstrated. In this study, the effect of radiation
      and oxidative stress on transgenic Escherichia coli expressing pprA has been
      studied. The pprA gene from D. radiodurans KR1 was cloned and expressed in E.
      coli. Transgenic E. coli cells expressing PprA showed twofold to threefold higher
      tolerance to hydrogen peroxide as compared to control. The 2.8-fold in vivo
      stimulation of catalase activity largely contributed by KatE was observed as
      compared to nonrecombinant control. Furthermore, the purified PprA could
      stimulate the E. coli catalase activity by 1.7-fold in solution. The effect of
      PprA on catalase activity observed both in vivo and in vitro was reverted to
      normal levels in the presence of PprA antibodies. The results suggest that
      enhanced oxidative stress tolerance in E. coli expressing PprA was due to the
      PprA stimulation of catalase activity, perhaps through the interaction of these
      proteins.

PMID- 16586107
TI  - Expression of Helicobacter pylori cag12 gene in Lactococcus lactis MG1363 and its
      oral administration to induce systemic anti-Cag12 immune response in mice.
AB  - To develop an oral vaccine against Helicobacter pylori infection, we have
      expressed the H. pylori cag12 (HP0532) gene, encoding the outer membrane protein
      Cag12 (31 kDa), in a live delivery vehicle Lactococcus lactis. The cag12 gene was
      amplified by polymerase chain reaction (PCR) using the genomic DNA of H. pylori
      K51 isolated from Korean patients. DNA sequence analysis revealed that the cag12
      gene of H. pylori K51 has 98.1 and 97.4% identity with individual cag12 genes of
      the H. pylori 26695 and J99, respectively. The GST-Cag12 fusion protein, produced
      using the Escherichia coli expression system, was used to raise a rat polyclonal
      anti-Cag12 antibody. The PCR-amplified cag12 gene of H. pylori K51 was cloned in
      the E. coli-L. lactis shuttle vector (pMG36e) and transformed into L. lactis.
      Western blot analysis demonstrated that the Cag12 protein was expressed in the L.
      lactis transformant, with a maximum level at the log phase without extracellular
      secretion. The oral administration of the transformant into mice resulted in the
      generation of the anti-Cag12 antibody in serum in two out of five cases. These
      results suggest that the recombinant L. lactis, which expresses Cag12, may be
      applicable as an oral vaccine to induce protective immunity against H. pylori.

PMID- 16586108
TI  - Correction of flexible thoracic scoliosis below 65 degrees--a radiological
      comparison of anterior versus posterior segmental instrumentation applied to
      similar curves.
AB  - Direct comparison of the correction of scoliosis achieved by different surgical
      methods is usually limited by the heterogeneity of the patients analyzed (their
      age, curve pattern, curve magnitude, etc.). The hypothesis is that an analysis of
      comparable scoliotic curves treated by different implant systems could detect
      subtle differences in outcome. The objective of this study was therefore: (1) to
      measure the 3D radiological parameters of scoliotic deformity and to quantify
      their postoperative changes, and (2) to compare the radiographic results achieved
      with one anterior and one posterior instrumentation methods applied to similar
      curves but representing different mechanisms of correction. MATERIAL AND METHODS:
      The clinical notes and radiographs of 46 patients operated on for adolescent
      idiopathic scoliosis were reviewed. The inclusion criteria consisted of: a single
      thoracic curve, right convex, a frontal Cobb angle minimum of 45 degrees and a
      maximum of 65 degrees , flexibility on a lateral bending test of more than 30%,
      and a Risser test value of between 1 and 4. The operative procedures were: Cotrel
      Dubousset instrumentation (CDI) for 25 patients (the CD group) and correction by
      anterior instrumentation (Pouliquen plate) for 21 patients (the ANT group).
      Preoperative and postoperative long cassette standing antero-posterior and
      lateral radiographs were examined. The frontal and sagittal thoracic Cobb angle,
      apical vertebra transposition (AVT), apical vertebra rotation (AVR), lowest
      instrumented vertebra (LIV) tilt, C7 vertebra shift and rib cage shift (RCS) were
      all compared. A computed reconstruction was produced with Rachis-91 software.
      Vertebral axial rotation angle was evaluated throughout the spine. RESULTS:
      Postoperative assessment revealed a mean correction of the frontal Cobb angle of
      37.0 degrees for the CD group and 41.0 degrees for the ANT group. The AVT
      operative correction was 45.8 and 42.7 mm, respectively, and AVR correction was
      1.8 and 12.6 degrees , respectively. The postoperative change of the sagittal Th4
      Th12 Cobb angle was not significant for any method but it was significant
      (P=0.05) for the CD group if the curves were divided preoperatively into
      hypokyphotic and normokyphotic subgroups and then analyzed separately. Computed
      assessment demonstrated a correction of segmental axial rotation of more than 50%
      in the main thoracic curve in the ANT group, significantly more than that in the
      CD group (P<0.001). CONCLUSIONS: Anterior instrumentation provided better
      correction of the vertebral axial rotation and of the rib hump. CD
      instrumentation was more powerful in translation and more specifically addressed
      the sagittal plane: the postoperative thoracic kyphosis angle increased in the
      hypokyphotic curves and slightly decreased in the normokyphotic curves.

PMID- 16586109
TI  - Epstein-Barr viral load in whole blood of adults with posttransplant
      lymphoproliferative disorder after solid organ transplantation does not correlate
      with clinical course.
AB  - Posttransplant lymphoproliferative disease (PTLD) is closely linked to primary
      Epstein-Barr virus (EBV) infection. A defect of EBV specific cellular immunity is
      postulated to play a pivotal role in the etiology of PTLD, but there is some
      debate as to whether EBV load in the peripheral blood of transplant patients
      predicts onset of PTLD or relapse after treatment. The current prospective,
      single-center study was undertaken to investigate the impact of therapy on EBV
      load in adult patients with PTLD. Fifteen patients with PTLD after solid organ
      transplantation were included and of these, seven had EBV-associated PTLD. All 15
      patients received Rituximab as primary therapy. In cases of treatment failure or
      relapse after Rituximab treatment, patients received polychemotherapy according
      to the cyclophosphamide, vincristine, doxorubicin, and prednisone regimen. At
      onset of PTLD, the median EBV load in the peripheral blood of patients was higher
      in EBV-associated PTLD than PTLD with no associated EBV infection. After
      Rituximab therapy, four of seven patients with EBV-associated PTLD achieved long
      lasting complete remissions. However, in two of these patients, EBV load
      increased to reach levels as high as those recorded at onset of PTLD. Another
      patient showed a dramatic decline of EBV load after the first dose of Rituximab
      while suffering from progressive disease. The other patient relapsed after
      Rituximab monotherapy, but his viral load stayed low. In total, discordance in
      EBV load and clinical course was observed in five of the seven patients with EBV
      associated PTLD. We conclude that in adult patients with PTLD, EBV load does not
      correlate with treatment response and is not suitable as a predictive marker for
      PTLD relapse.

PMID- 16586110
TI  - Involvement of cytoskeletal proteins and growth factor receptors during
      development of the human eye.
AB  - The spatial and temporal distribution of nestin, cytokeratins (CKs), vimentin,
      glial fibrillary acidic protein (GFAP), neurofilaments (NFs), beta-tubulin as
      well as fibroblast growth factor receptors (FGFRs) and platelet-derived growth
      factor receptor beta (PDGF-Rbeta) were investigated in the developing human eye
      in eight conceptuses of 5-9 postovulatory weeks using immunostaining. Nestin was
      found in the neuroglial precursors and the radial glial fibres of the optic
      nerve. In the pigmented retina, nestin was present only in the 5th week, while at
      later stages (6-9th week), co-expression of CKs and vimentin was seen. Nestin,
      CKs, vimentin, and GFAP were observed in the precursors to various cell types in
      the neural retina. Additionally, their expression was also apparent in the lens
      epithelium, showing its gradual fading following the lens fibre elongation. They
      appeared in the mesenchymal cells of the cornea, the choroid, the sclera, and the
      corpus vitreum, too. In the corneal epithelium, co-expression of nestin and CKs
      was detected. NFs and beta-tubulin were confined to the differentiating retinal
      neuroblasts. Growth factor receptors were seen in the retina, the lens epithelium
      while less intensely in the lens fibres, the corneal epithelium, and the
      mesenchymal cells. During the early eye development (5-9th week), IFs expressing
      normal pattern of distribution as well as acting in concert might contribute to
      the normal developmental processes occurring in certain parts of the human eye.
      Additionally, NFs and beta-tubulin seem to have an important role in the retinal
      ganglion cell differentiation, while FGFRs and PDGF-Rbeta may regulate the cell
      proliferation, differentiation, and survival in various parts of the developing
      eye.

PMID- 16586111
TI  - Leaf strategies and soil N across a regional humidity gradient in Patagonia.
AB  - We analyzed leaf traits related to carbon-fixation, nutrient conservation
      strategies, and decomposability and their relationships with potential N
      mineralization and microbial N in soil in 19 species of 5 dominant life forms
      growing in 40 sites across a regional humidity gradient in northern Patagonia. We
      hypothesized that (1) the shifting of species and life forms across the humidity
      gradient is related to a shifting in traits of green and senesced leaves with
      some overlapping among life forms, and (2) leaf traits associated with litter
      decomposition are related to the potential dynamics of soil-N across the humidity
      gradient. LMA in green leaves and P-resorption efficiency decreased with humidity
      while concentrations of lignin and total phenolics in green and senesced leaves
      and P concentration in senesced leaves increased with humidity. Soil C and N
      concentrations were positively correlated to humidity. Increasing soil N
      concentration was related to increasing rates of absolute (per unit soil mass)
      potential net N-mineralization and microbial-N flush. Relative (per unit N mass)
      potential net N-mineralization and microbial-N flush decreased with soil N and
      were inversely correlated to lignin concentration and C/N ratio in senesced
      leaves. We found overlapping in N concentration and C/N ratio in green and
      senesced leaves, P concentration in green leaves, and N resorption among species
      and life forms across the humidity gradient. We concluded that (1) leaf traits
      related to carbon fixation and the decomposition pathway significantly varied
      with humidity and were not overlapped between plant life forms from dry and humid
      habitats, (2) the largest overlapping among species and plant life forms across
      the gradient occurred in those leaf traits related to N conservation in the
      plant, and (3) life forms from humid habitats produce more recalcitrant litter
      that induce lower rates of relative potential net N mineralization (per unit N)
      than those of dry habitats.

PMID- 16586112
TI  - Plankton motility patterns and encounter rates.
AB  - Many planktonic organisms have motility patterns with correlation run lengths
      (distances traversed before direction changes) of the same order as their
      reaction distances regarding prey, mates and predators (distances at which these
      organisms are remotely detected). At these scales, the relative measure of run
      length to reaction distance determines whether the underlying encounter is
      ballistic or diffusive. Since ballistic interactions are intrinsically more
      efficient than diffusive, we predict that organisms will display motility with
      long correlation run lengths compared to their reaction distances to their prey,
      but short compared to the reaction distances of their predators. We show motility
      data for planktonic organisms ranging from bacteria to copepods that support this
      prediction. We also present simple ballistic and diffusive motility models for
      estimating encounter rates, which lead to radically different predictions, and we
      present a simple criterion to determine which model is the more appropriate in a
      given case.

PMID- 16586114
TI  - Inactivation of an invertebrate acetylcholinesterase by sulfhydryl reagents: the
      roles of two cysteines in the catalytic gorge of the enzyme.
AB  - We have used site-directed mutagenesis and molecular modeling to investigate the
      inactivation of an invertebrate acetylcholinesterase (AChE), ChE2 from amphioxus,
      by the sulfhydryl reagents 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and N
      ethylmaleimide (NEM), creating various mutants, including C310A and C466A, and
      the double mutants C310A/C466A and C310A/F312I, to assess the relative roles of
      the two cysteines and a proposal that the increased rate of inactivation in the
      F312I mutant is due to increased access to Cys310. Our results suggest that both
      cysteines may be involved in inactivation by sulfhydryl reagents, but that the
      cysteine in the vicinity of the acyl pocket is more accessible. We speculate that
      the inactivation of aphid AChEs by sulfhydryl reagents is due to the presence of
      a cysteine homologous to Cys310. We also investigated the effects of various
      reversible cholinergic ligands, which bind to different subsites of the active
      site of the enzyme, on the rate of inactivation by DTNB of wild type ChE2 and
      ChE2 F312I. For the most part the inhibitors protect the enzymes from
      inactivation by DTNB. However, a notable exception is the peripheral site ligand
      propidium, which accelerates inactivation in the wild type ChE2, but retards
      inactivation in the F312I mutant. We propose that these opposing effects are the
      result of an altered allosteric signal transduction mechanism in the F312I mutant
      compared to the wild type ChE2.

PMID- 16586113
TI  - The heme environment of mouse neuroglobin: histidine imidazole plane orientations
      obtained from solution NMR and EPR spectroscopy as compared with X-ray
      crystallography.
AB  - The 1H NMR chemical shifts of the heme methyl groups of the ferriheme complex of
      metneuroglobin (Du et al. in J. Am. Chem. Soc. 125:8080-8081, 2003) predict
      orientations of the axial histidine ligands (Shokhirev and Walker in J. Biol.
      Inorg. Chem. 3:581-594, 1998) that are not consistent with the X-ray data
      (Vallone et al. in Proteins Struct. Funct. Bioinf. 56:85-94, 2004), and the EPR
      spectrum (Vinck et al. in J. Am. Chem. Soc. 126:4516-4517, 2004) is only
      marginally consistent with these data. The reasons for these inconsistencies
      appear to be rooted in the high degree of aqueous solution exposure of the heme
      group and the fact that there are no strong hydrogen-bond acceptors for the
      histidine imidazole N-H protons provided by the protein. Similar inconsistencies
      may exist for other water-soluble heme proteins, and 1H NMR spectroscopy provides
      a simple means to verify whether the solution structure of the heme center is the
      same as or different from that in the crystalline state.

PMID- 16586115
TI  - Construction of a quinoa (Chenopodium quinoa Willd.) BAC library and its use in
      identifying genes encoding seed storage proteins.
AB  - Quinoa (Chenopodium quinoa Willd.) is adapted to the harsh environments of the
      Andean Altiplano region. Its seeds have a well-balanced amino acid composition
      and exceptionally high protein content with respect to human nutrition. Quinoa
      grain is a staple in the diet of some of the most impoverished people in the
      world. The plant is an allotetraploid displaying disomic inheritance (2n=4x=36)
      with a di-haploid genome of 967 Mbp (megabase pair), or 2C=2.01 pg. We
      constructed two quinoa BAC libraries using BamHI (26,880 clones) and EcoRI
      (48,000 clones) restriction endonucleases. Cloned inserts in the BamHI library
      average 113 kb (kilobase) with approximately 2% of the clones lacking inserts,
      whereas cloned inserts in the EcoRI library average 130 kb and approximately 1%
      lack inserts. Three plastid genes used as probes of high-density arrayed blots of
      73,728 BACs identified approximately 2.8% of the clones as containing plastid DNA
      inserts. We estimate that the combined quinoa libraries represent at least 9.0 di
      haploid nuclear genome equivalents. An average of 12.2 positive clones per probe
      were identified with 13 quinoa single-copy ESTs as probes of the high-density
      arrayed blots, suggesting that the estimate of 9.0x coverage of the genome is
      conservative. Utility of the BAC libraries for gene identification was
      demonstrated by probing the library with a partial sequence of the 11S globulin
      seed storage protein gene and identifying multiple positive clones. The presence
      of the 11S globulin gene in four of the clones was verified by direct comparison
      with quinoa genomic DNA on a Southern blot. Besides serving as a useful tool for
      gene identification, the quinoa BAC libraries will be an important resource for
      physical mapping of the quinoa genome.

PMID- 16586116
TI  - Silent microemboli related to diagnostic cerebral angiography: a matter of
      operator's experience and patient's disease.
AB  - INTRODUCTION: The aim of the present investigation was to elucidate in a large
      consecutive patient cohort whether the level of training has an effect on the
      number of microemboli detected by diffusion-weighted imaging (DWI) and which
      additional risk factors can be identified. METHODS: A total of 107 consecutive
      patients in whom a diagnostic cerebral angiography had been performed were
      prospectively investigated with DWI; 51 angiographies were performed by
      experienced neuroradiologists, 56 by neuroradiologists in training. RESULTS: In
      12 patients (11.1%), a total of 17 new lesions without any clinically overt
      neurological symptoms were identified. Of these, 12 patients, 11 (91.7%) with 16
      lesions were investigated by junior neuroradiologists. In 11 of 12 patients with
      DWI abnormalities (91.7%), risk factors could be identified (atherosclerotic
      vessel wall disease, vasculitis, hypercoagulable states). Experienced
      neuroradiologists performed 21 of 48 angiographies (43.8%) on patients with the
      above-mentioned risk factors, whereas junior neuroradiologists performed 27
      angiographies in this subgroup (46.2%). The rate of diffusion abnormalities in
      patients with risk factors was 11/48 (22.9%) - considerably higher than in
      patients without risk factors (1/59; 1.7%). CONCLUSION: The level of experience
      and the nature of the underlying disease are predictors of the occurrence of
      cerebral ischemic events following neuroangiography. Alternative diagnostic
      modalities should be employed in patients who are investigated for diseases with
      the highest risk of angiographic complications (i.e., vasculitis, and
      arteriosclerotic vessel wall disease). If diagnostic angiography remains
      necessary in these patients, the highest level of practitioner training is
      necessary to ensure good patient outcome.

PMID- 16586117
TI  - Expanding the treatment window with mechanical thrombectomy in acute ischemic
      stroke.
AB  - INTRODUCTION: Acute ischemic stroke is a common disease associated with high
      mortality and significant long-term disability. Treatment options for acute
      ischemic stroke continue to evolve and include pharmaceutical and mechanical
      therapies. With the recent US Food and Drug Administration approval of a new
      device for mechanical thrombectomy, the options available for treatment of acute
      ischemic stroke have been expanded. Thrombolytic therapy is generally given
      intravenously in the first 3 h and up to 6 h via the intraarterial route for
      pharmacological clot disruption. The maximum time-frame for mechanical
      thrombectomy devices has yet to be determined. METHODS: A 78-year-old female
      presented to the emergency room with a dense right hemiparesis, leftward gaze
      preference and dense global aphasia. Eight hours after symptom onset, left
      carotid angiography confirmed a left internal carotid artery terminus occlusion.
      A single pass was made through the clot with an X6 Merci Retriever device.
      RESULTS: After a single pass, the vessel was reopened and normal flow in the left
      internal carotid artery was demonstrated. At the time of discharge, her
      neurological deficits had improved significantly. Furthermore, the final infarct
      area, as demonstrated on magnetic resonance imaging, was probably much smaller
      than it would have been if the vessel had not been recanalized. CONCLUSION: We
      report the use of a new mechanical thrombectomy device 8 h after onset of
      ischemic symptoms, with substantial subsequent improvement in neurological
      outcome. In selected cases, use of the Merci Retriever can result in improved
      outcomes beyond the traditional 6-h window used for intraarterial pharmacological
      thrombolysis.

PMID- 16586118
TI  - Serial MRI of limbic encephalitis.
AB  - INTRODUCTION: The aim of the study was to analyze serial magnetic resonance
      imaging (MRI) scans in patients with various forms of limbic encephalitis (LE) in
      order to evaluate whether, and at what time point, MRI findings support the
      diagnosis of LE. METHODS: Serial MRI scans (1 day to 15 years after the onset of
      symptoms) of 20 patients with LE were retrospectively evaluated. Of these 20
      patients, 16 had definite LE (histopathological limbic inflammation, n=6;
      onconeural antibodies, n=5; voltage-gated potassium channel antibodies, n=3;
      malignant tumors, n=5), and 4 possible LE because they met the clinical criteria
      but had no typical antibodies or tumors. RESULTS: Of 13 patients who were studied
      with MRI within 3 months after the onset of symptoms, 11 had swollen
      temporomesial structures (unilateral, n=7; bilateral, n=4). After up to 9 months,
      the swelling had resolved in nine of ten re-evaluated patients. Of seven patients
      who were initially studied with MRI more than 3 months after disease onset, three
      had swollen temporomesial structures, one had a hyperintense, normal-sized
      hippocampus, and three had hyperintense and atrophic temporomesial structures.
      CONCLUSION: LE starts as an acute disease with uni- or bilateral swollen
      temporomesial structures that are hyperintense on fluid attenuation inversion
      recovery and T2-weighted sequences. Swelling and hyperintensity may persist over
      months to years, but in most cases progressive temporomesial atrophy develops.

PMID- 16586119
TI  - Positive correlations between cerebral choline and renal dysfunction in chronic
      renal failure.
AB  - INTRODUCTION: Cerebral metabolism in chronic renal failure (CRF) patients has not
      been fully evaluated. This study examined cerebral metabolites in CRF, using
      proton magnetic resonance spectroscopy (MRS). METHODS: Subjects comprised 19 CRF
      patients and 21 healthy volunteers. Spectra were acquired from voxels of interest
      positioned in the parietal gray and white matter, and concentrations of the
      following cerebral metabolites were measured: N-acetyl group (NA), creatine +
      phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol and
      glutamate + glutamine. Among the 19 CRF patients, 9 who were started on
      hemodialysis (HD) underwent careful follow-up. Proton MRS was performed before
      and about 2 weeks after starting HD. In six patients in whom follow-up was
      possible, a third MRS was performed after about 18 months. RESULTS: The NA/Cr
      ratio was not significantly changed in CRF. However, elevations in the Cho/Cr
      ratio were found in both gray and white matter compared with controls. To the
      best of our knowledge, this is the first report of positive correlations between
      the Cho/Cr ratio in both regions and serum osmotic pressure. Compared with
      baseline data, no significant changes in cerebral metabolite ratios were found
      about 2 weeks after starting HD. About 18 months after starting HD, however, the
      elevated Cho/Cr ratio was significantly reduced in the gray matter and tended to
      be reduced in the white matter. CONCLUSIONS: Cho appear to play an important role
      in the regulation of cerebral metabolism to compensate for alterations in serum
      osmotic pressure in CRF, and HD may correct this abnormal cerebral metabolism.

PMID- 16586120
TI  - Avian magnetic compass: fast adjustment to intensities outside the normal
      functional window.
AB  - To determine how fast birds can adapt to magnetic intensities outside the normal
      functional window of their magnetic compass, we tested migratory birds in a
      magnetic field of 92,000 nT, twice the intensity of the local geomagnetic field
      at the test site in Frankfurt a.M., Germany. In the local field, robins showed a
      significant preference of their southerly migratory direction, whereas in the
      92,000-nT field, they were initially disoriented. However, when the birds were
      preexposed to 92,000 nT for 1 h before being tested, they were able to orient
      under this intensity, and their behavior did not differ from that in the
      geomagnetic field. These data show that birds require only a short time to adjust
      to magnetic intensities, which they cannot spontaneously use for orientation.
      Interpreting these findings in view of the radical pair model (Ritz et al. 2000),
      this means that they can learn rather quickly to interpret novel activation
      patterns on their retina.

PMID- 16586121
TI  - The concept of constant emission yield in GDOES.
AB  - This review paper describes the evolution of the quantification procedure for
      compositional depth profiling (CDP) in glow discharge optical emission
      spectrometry (GD-OES), based on the constant emission yield concept. The concept
      of emission yield (EY) is defined and ways of measuring it experimentally are
      discussed. The history of the development of quantitative CDP is reviewed, which
      shows that all of the different approaches depend on the assumption that the EY
      is essentially a matrix-independent quantity. Particular emphasis is placed on
      the dependence of the EY on the plasma parameters of current, voltage, power and
      pressure. In short, impedance changes (current voltage) can significantly affect
      the emission yield and should either be corrected mathematically or the impedance
      should be kept constant by pressure regulation in order to obtain reliable
      results from GDOES CDP. On the other hand, the effect of varying the pressure on
      the emission yield can be considered to be minor within the limits of practical
      operating conditions for most CDP applications. It is worth, however, bearing in
      mind that varying the discharge pressure has a significant effect on the plasma
      processes, and does affect the emission yield when these variations are large.
      The experimental results obtained for the emission yield are related to the
      results from theoretical model calculations published on the subject.

PMID- 16586122
TI  - Amifostine in the management of radiation-induced and chemo-induced mucositis.
AB  - INTRODUCTION: Mucositis is a significant complication of cancer therapy, with
      important clinical and economic implications. In June 2005, the Mucositis Study
      Group of the Multinational Association of Supportive Care in Cancer/International
      Society for Oral Oncology (MASCC/ISOO) conducted an evidence-based update review
      of the literature on mucositis. The goal of this literature review is to update
      previously published guidelines for the management of mucositis. RESULTS: This
      article reports the findings of the subgroup charged with reviewing the
      literature related to amifostine.

PMID- 16586129
TI  - [Meeting of the Department of Dermatology, University of Aachen].

PMID- 16586131
TI  - [Is activated protein C useful in low mortality risk?].

PMID- 16586130
TI  - [Hyperuricemia and gout: diagnosis and therapy].
AB  - In our modern society hyperuricemia is one of the most frequent metabolism
      disturbances. So far, every fourth man and every tenth woman suffer from an
      asymptomatic or a symptomatic hyperuricemia named gout. Mostly, over nutrition
      and malnutrition as well as other secondary factors with a genetically determined
      renal secretion disturbance of uric acid lead to an increase of serum uric acid.
      By deposition of uric acid crystals in tissues with intermittent immunologic
      activation of inflammation cells a manifestation of gout can be seen. The
      clinical image of gout varies widely. It may manifest as acute or chronic
      arthritis, tophi on the skin, subcutaneous tissue and the skeletal system as well
      as urate nephropathy. To eliminate the consequences of hyperuricemia in the long
      term, apart from a thorough anamnesis of nutritional habits a general examination
      of metabolic parameters is necessary to exclude a metabolic syndrome and other
      causes for a secondarily caused hyperuricemia. As gout is very often primarily
      caused by a renal secretion disturbance of uric acid special diagnostics should
      be done. Basing on literature research and inclusion of experts opinions this
      article represents the therapeutically options in treatment of hyperuricemia and
      gout with their resulting side effects and contraindications.

PMID- 16586134
TI  - Floating knee injuries: more than what meets the eye.

PMID- 16586132
TI  - Outcome following deep wound contamination in cemented arthroplasty.
AB  - Infection remains a devastating complication of joint replacement surgery causing
      a significant burden to both patient and surgeon. However, despite exhaustive
      prophylactic measures, intraoperative contamination still occurs during cemented
      arthroplasty with current infection rates of 1-2%. A study was undertaken to
      determine the incidence of perioperative contamination in cemented arthroplasty
      patients, to identify contaminating organisms, to identify contaminated regions
      within the operative wound, to identify factors associated with increased
      contamination, and finally to assess the medium-term clinical outcome in patients
      with confirmed intraoperative wound contamination. Eighty consecutive patients
      undergoing hip and knee cemented arthroplasty were prospectively enrolled over a
      6-month period. All scrubbed personnel wore total body exhaust isolation suits
      and procedures were carried out in ultra-clean air theatres. Of 441 samples,
      contamination was identified at 21 sites (4.8%) representing a cohort of 18
      patients (22.5%). Longer duration of surgery predisposed to higher contamination
      rates while lower contamination rates were significantly related to fewer gowned
      personnel within the ultra-clean system, and fewer total personnel in theatre
      during the procedure. None of the patients developed clinical evidence of deep
      prosthetic infection at follow-up. We noted a high incidence of intraoperative
      contamination despite standard prophylaxis. However, this was not reflected by a
      similar rate of postoperative infection. This may be due to a small bacterial
      inoculum in each case or may be due to the therapeutic effect of perioperative
      intravenous antibiotic prophylaxis.

PMID- 16586133
TI  - The alpha2 type IX collagen tryptophan polymorphism is associated with the
      severity of disc degeneration in younger patients with herniated nucleus pulposus
      of the lumbar spine.
AB  - Tryptophan alleles in COL9A2 (Trp2) and COL9A3 (Trp3) have been linked to lumbar
      disc diseases in the Finnish population. Although such diseases consist of
      various pathogenetically different conditions, detailed analysis of each has not
      been well documented. The aim of this study was to clarify whether the collagen
      IX tryptophan alleles influence the symptomatic degeneration of the lumbar disc
      in Japanese patients with herniated nucleus pulposus. We performed a prospective
      study of 84 patients who underwent lumbar discectomy. The degree of disc
      degeneration was evaluated by magnetic resonance images in relation to the
      collagen IX genotype. Twenty patients (21.4%) had the Trp2 allele and no patients
      had the Trp3 allele. Patients under 40 years with the Trp2 allele showed more
      severe disc degeneration at the surgical level than did those without the Trp2
      allele (odds ratio 6.00, P=0.043). In contrast, patients aged 40 years or over
      did not show significant association between disc degeneration and collagen IX
      genotype. Our results suggest that the Trp2 allele is an age-dependent risk
      factor for the severity of disc degeneration in younger patients with symptomatic
      herniated nucleus pulposus of the lumbar spine.

PMID- 16586135
TI  - Stability of anterior vertebral body screws after kyphoplasty augmentation. An
      experimental study to compare anterior vertebral body screw fixation in soft and
      cured kyphoplasty cement.
AB  - The goal of this cadaver study was to compare the stability of anterior vertebral
      body screws after implantation in soft or cured kyphoplasty cement. Anterior
      vertebral body screws were inserted in a total of 30 thoracolumbar vertebrae of
      ten different human specimens: ten screws were implanted in non-augmented
      vertebrae (group 1), ten screws were placed in soft cement (group 2), and ten
      screws were placed in cured cement (group 3). The screws were then tested for
      biomechanical axial pullout resistance. Mean axial pullout strength was 192 N
      (range: 10-430 N) in group 1, 364 N (range: 65-875 N) in group 2, and 271 N
      (range: 35-625 N) in group 3. The paired Student's t-test demonstrated a
      significant difference between pullout strength of groups 1 and 2 (p= 0.0475). No
      significant difference was seen between pullout strength of groups 1 and 3 (p=
      0.2646) and between groups 2 and 3 (p= 0.3863). We achieved a 1.9 times higher
      pullout strength with kyphoplasty augmentation of osteoporotic vertebrae compared
      with the pullout strength of non-augmented vertebrae. Implantation of anterior
      vertebral body screws in cured cement is a satisfactory method. With this method
      we found a 1.4 times higher pullout strength than non-augmented vertebrae.

PMID- 16586136
TI  - Follow-up assessment of CPAP efficacy in patients with obstructive sleep apnea
      using an ambulatory device based on peripheral arterial tonometry.
AB  - This study aimed to assess the accuracy of a wrist-worn device based on
      peripheral arterial tonometry (Watch_PAT 100) to detect residual episodes of
      respiratory disturbance during continuous positive airway pressure (CPAP)
      therapy. Concurrent polysomnography was used as the reference standard to
      identify sleep disordered breathing (SDB) events. The study was conducted in
      three sleep laboratories affiliated with tertiary care academic medical centers.
      Seventy patients using CPAP to treat obstructive sleep apnea for at least 3
      months, following an in-laboratory titration to determine the optimal therapeutic
      positive airway pressure, participated in this study. Symptoms indicating
      suboptimal therapy were not required for participation, but self-reported
      adherence to CPAP therapy was necessary for inclusion. Interventions are not
      applicable in this study. The accuracy of the PAT-derived respiratory disturbance
      index (PAT RDI scored by automated algorithm) to detect residual SDB on CPAP was
      assessed against polysomnography (PSG) using Bland-Altman analysis, receiver
      operator characteristic (ROC) curves, and likelihood ratios for increasing (LR+)
      and decreasing (LR-) the probability of moderate-severe SDB in the study
      population. Respiratory events on the PSG were quantified using standard criteria
      for research investigations ("Chicago criteria") to yield a PSG RDI.C. Based on
      the PSG results, 19% of the participants had moderate-severe SDB (PSG RDI.C>15
      events per hour) on their prescribed pressure. For PAT RDI >15 events per hour,
      the area under the ROC curve was 0.95 (SE 0.03, p < 0.0001, 95% CI 0.89 to 1.00),
      the LR+ was 8.04 (95% CI 3.64-17.7), and the LR- was 0.17 (95% CI 0.05-0.62). The
      mean difference between the PAT RDI and PSG RDI.C was three (2SD 14.5) events per
      hour. Therefore, residual moderate-severe SDB on CPAP was not uncommon in a
      multicenter population self-reporting adherence to CPAP therapy to treat
      obstructive sleep apnea. The Watch_PAT device accurately identified participants
      with moderate-severe SDB while using CPAP in the attended setting of a sleep
      laboratory.

PMID- 16586137
TI  - Prognostic factors affecting urologic outcome after untethering surgery for
      lumbosacral lipoma.
AB  - OBJECTS: The authors report results of preoperative and postoperative urodynamic
      studies (UDS) and prognostic factors of urologic outcome in cases of lumbosacral
      lipomas for which prolonged follow-up data were available. MATERIALS AND METHODS:
      The present series includes 42 consecutive cases of lumbosacral lipoma in
      patients aged 2 months to 15 years who underwent untethering operation during the
      period from 1986 to 1997. All of them underwent preoperative and postoperative
      UDS. At the last follow-up (mean duration of follow-up 108 months, range 44 to
      176 months), 26 cases maintained social continence with or without intermittent
      catheterization. Young age (< or =12 months) at operation, preoperative absence
      of urologic symptoms, and absence of neurologic abnormalities were significantly
      correlated with favorable urologic outcome. CONCLUSION: UDS in cases with
      lumbosacral lipomas is a valuable tool for detecting neurourologic abnormalities
      as well as for monitoring the postoperative course and guiding management.
      History taking and neurologic examination are also proved to be important aspects
      in the evaluation of children with lumbosacral lipomas, predictive of urologic
      outcome. Better urologic results are anticipated if surgery is performed when the
      child is 12 months old or younger.

PMID- 16586138
TI  - Spinal arteriovenous shunts presenting before 2 years of age: analysis of 13
      cases.
AB  - BACKGROUND AND PURPOSE: A minority of patients with spinal arteriovenous
      malformations (SAVM) are symptomatic as neonates or infants. We analyzed the
      clinical and anatomic factors associated with this early presentation, and
      reviewed our experience in treating patients with these lesions. METHODS: A
      retrospective review of clinical records and imaging studies was performed for
      patients with SAVM who presented at less than 2 years of age and who were
      examined by the diagnostic and interventional neuroradiology service at our
      institution. Clinical, imaging and treatment data had been entered prospectively
      into a department database. RESULTS: Thirteen patients were identified that had
      SAVMs that were either diagnosed or that became symptomatic before 2 years of age
      (nine boys, four girls). These represented 13% of the SAVM seen during the same
      period of time. The mean age at presentation was 6.9+/-6.4 months. Of the 13
      patients, 11 had neurologic symptoms attributable to the spinal lesion. The
      presentation was nonhemorrhagic in ten patients and associated with hemorrhage in
      three. Ten lesions were fistulas [spinal cord arteriovenous fistulas (SCAVFs)]
      (77%); two were of the nidus type of malformation. There were syndromic
      associations in eight patients: hereditary hemorrhagic telangectasia (HHT) in six
      patients, all but one of these lesions were intradural high-flow perimedullary
      SCAVFs (46% of overall SAVM and 56% of SCAVF), and spinal arteriovenous metameric
      syndrome in two patients. One patient had Hirschprung's anomaly. Eight patients
      underwent endovascular treatment alone, one had surgery and embolization, and
      four were not treated. In all patients undergoing embolization, n-butyl
      cyanoacrylate liquid adhesive was used. Of those patients who underwent
      endovascular treatment, the lesion was completely obliterated in 7 and a 90%
      reduction in nidal size was achieved in the remaining 2. There was one treatment
      complication (infection) which resolved with medical therapy. No procedure
      related permanent morbidity or mortality was seen. Follow-up data were available
      (mean 31.4 months) in ten patients (nine treated). All treated patients were
      either stable or improved, with none showing further deterioration following
      treatment. CONCLUSION: Factors associated with early presentation in neonates and
      infants with spinal arteriovenous shunts include the presence of high-flow,
      solitary fistulas and HHT. Specifically, the presence of SCAVF in a child less
      than 2 years of age is highly suggestive of HHT. Despite the aggressive nature of
      these lesions, many are amenable to endovascular treatment, and this is
      associated with a favorable posttreatment course in most cases.

PMID- 16586140
TI  - Managing tree-of-heaven (Ailanthus altissima) in parks and protected areas: a
      case study of Rondeau Provincial Park (Ontario, Canada).
AB  - The Carolinian Life Zone in southwestern Ontario, Canada is valued because it
      represents an almost disjunct ecosystem (i.e., one that is typical of the mid
      Atlantic United States, rather than the rest of Canada or the nearby states in
      the United States). The landscape of the Carolinian Life Zone has undergone
      dramatic transformation, especially in recent decades as agriculture,
      urbanization, and recreation have intensified. One of the most apparent changes
      is the invasion of exotic plant species that exacerbates the need for mass
      restoration efforts. Within the Carolinian Life Zone, Rondeau Provincial Park has
      experienced an influx of nonindigenous, invasive species in recent years. Tree-of
      heaven (Ailanthus altissima) is one example. The infestation is still relatively
      localized to (mainly) the park, slowly spreading, and manageable as long as
      something is done immediately. We examined the effects of hand-pulling and
      mulching, cut stump and glyphosate application, cut stump alone, and the EZJect
      Capsule Injection System (using glyphosate) on the management of A. altissima
      within the park. Cut stump and glyphosate treatment was most effective and
      efficient in its control of young A. altissima shoots because it limits
      disturbance and has acceptable capital and operating costs. Hand-pulling and
      mulching was the second choice, mainly because of the risk of additional
      disturbance that increased shoot densities 1 year after treatment. Cut stump
      alone was not effective, worsened the infestation, and is not recommended for
      this species. The EZJect system was effective at managing mature, seed-producing
      shoots, although the somewhat higher capital costs mean that the system probably
      should be purchased for management of several invasive tree species to make it
      more cost-effective.

PMID- 16586141
TI  - Successful voiding after trial without catheter is not synonymous with recovery
      of bladder function after colorectal surgery.
AB  - PURPOSE: The need for monitoring postoperative urine output and the possibility
      of lower urinary tract dysfunction following colorectal surgery necessitates
      temporary urinary drainage. Current practice assumes recovery of lower urinary
      tract function to coincide with successful micturition after removal of urethral
      catheter. The aim of this study was to analyze the recovery of bladder function
      following colorectal surgery. METHODS: Patients undergoing colorectal operations
      underwent preoperative and postoperative uroflowmetry and residual urine
      estimation. All patients were catheterized suprapubically at surgery.
      Uroflowmetry and postvoid residual volumes were recorded postoperatively until
      recovery of bladder function was complete. RESULTS: Thirty consecutive patients
      underwent suprapubic catheterization, 25 of whom completed the study. Seventeen
      (68 percent) patients were able to pass urine within 72 hours of surgery.
      Recovery of lower urinary tract function was delayed in patients undergoing
      rectal vs. colonic resections (median, 6 vs. 3 days, P = 0.0015). Postvoid
      residual volumes greater than 200 ml were noted in three (20 percent) patients
      following rectal resections beyond the tenth postoperative day, with complete
      emptying achieved by six weeks. CONCLUSIONS: Apparent successful micturition
      following rectal resections does not always indicate recovery of bladder
      function. The use of suprapubic catheters, in addition to being safe and
      effective, allows assessment of residual volumes postoperatively and smoothes the
      path to full recovery of lower urinary tract function.

PMID- 16586142
TI  - 13th International Congress of the European Association for Endoscopic Surgery
      and other Interventional Techniques (E.A.E.S.), Venice, Lido, Italy, 1-4 June
      2005. Abstracts.

PMID- 16586144
TI  - Association of Laparoscopic Surgeons of Great Britain and Ireland (ALSGBI),
      Galway, Ireland, United Kingdom, 17-18 November 2005. Abstracts.

PMID- 16586145
TI  - 2006 Scientific Session of the Society of American Gastrointestinal and
      Endoscopic Surgeons (SAGES), Dallas, Texas, USA, 26-29 April 2006. Abstracts.

PMID- 16586149
TI  - Is dopamine behind the health benefits of red wine?
AB  - BACKGROUND: The contribution of biologically active non-nutrient chemicals to the
      health benefits of the Mediterranean diet is controversial because of their low
      dietary concentrations. Hydroxytyrosol is a dopamine metabolite, and also a very
      active naturally occurring phenol compound in olive oil. AIM OF THE STUDY: To
      examine the disposition of hydroxytyrosol in humans, given that we discovered its
      presence in red wine in the frame of the study. METHODS: The pharmacokinetics of
      hydroxytyrosol from two clinical trials, designed to assess the short-term and
      postprandial effects of moderate doses of wine and olive oil in healthy
      volunteers, were compared. RESULTS: Despite a five-fold difference in the doses
      of hydroxytyrosol administered (0.35 mg for red wine and 1.7 mg for olive oil),
      urinary recoveries of hydroxytyrosol were higher after red wine administration.
      An interaction between ethanol and dopamine after red wine ingestion leading to
      the formation of hydroxytyrosol was observed. CONCLUSIONS: Biological effects
      after red wine ingestion should be re-examined on the basis of combined
      hydroxytyrosol concentrations from red wine and dopamine turnover.

PMID- 16586150
TI  - Entire potato consumption improves lipid metabolism and antioxidant status in
      cholesterol-fed rat.
AB  - BACKGROUND: Vegetables and fruits are rich sources of a variety of nutrients,
      including vitamins (E and C), trace minerals, and dietary fibers, and many other
      classes of biologically active compounds such as carotenoids and polyphenols,
      which are often assumed to protect against degenerative pathologies such as
      cardiovascular diseases. Although potato is considered as a starchy food, it is
      also included in the category of vegetables by its micronutrient content. AIM OF
      THE STUDY: In the present study, we investigated in the rat the effect of a
      potato-enriched diet on lipid metabolism and antioxidant protection. RESULTS:
      Feeding rats a potato-enriched diet for 3 weeks led to a significant decrease in
      cholesterol and triglyceride levels in plasma (respectively, -30%, P<0.0001 and 
      36%, P<0.05) and cholesterol level in liver (-42%, P<0.0001). Antioxidant status
      was also improved by potato consumption. TBARS levels in heart were decreased and
      vitamin E/triglycerides ratio in plasma was improved. CONCLUSIONS: Our present
      results suggest that consumption of cooked potatoes (consumed with skin) may
      enhance antioxidant defense and improve the lipid metabolism. These effects could
      be interesting for prevention of cardiovascular disease.

PMID- 16586151
TI  - A method for analyzing strain differences in acquisition of IV cocaine self
      administration in mice.
AB  - The techniques currently available for studying drug self-administration in
      animals offer the unique opportunity to carry out micro-analysis of initial
      episodes of drug use which are extremely difficult to obtain for human subjects.
      Nonetheless, traditional self-administration techniques do not allow a cost
      effective output of large sample sizes needed for genetic analysis. Additionally,
      the statistical techniques that allow the integration of within-subject temporal
      data with genetic information are scant. We therefore propose a two-stage method
      for analyzing strain differences in dynamic phenotypes for a high-throughput
      version of the self-administration procedure. On a first phenotype-refinement
      stage, a change-point algorithm (Gallistel et al. (2004) Proc. Natl Acad. Sci.
      USA 101:13124-13131) was used to separate individual drug self-administration
      response curves into three distinct components. In a second stage, strains
      differences in these indexes were assessed. This two-stage approach is
      illustrated with drug self-administration data and through a computer simulation.

PMID- 16586153
TI  - Laterality in persons with intellectual disability. I--do patients with trisomy
      21 and Williams-Beuren syndrome differ from typically developing persons?
AB  - Persons with trisomy 21 (T21) and Williams-Beuren syndrome (WBS) have different
      brain abnormalities which may affect manual laterality. We assessed 45 persons
      with T21 and 34 with WBS (mean age 13) and 81 typically developing children (TD).
      Manual laterality was assessed with a fifteen-item task administered two times,
      and Bishop's card-reaching task. We found more left-handers in the T21 group
      compared to the other two groups. Inconsistent laterality was higher in the two
      groups with genetic diseases than in the TD group. For Bishop's test, both T21
      and WBS participants were less right-oriented than the TD group. They displayed
      different response patterns in midline crossing when reaching for the cards, but
      did not display more midline crossing inhibition than the TD group. Is atypical
      handedness linked to specific genetic syndromes and, more specifically for
      persons with T21, to the trisomy of some of the genes?

PMID- 16586152
TI  - Genetic and environmental influences on stages of alcohol use across adolescence
      and into young adulthood.
AB  - The progression to alcohol dependence unfolds across multiple stages, including
      the decision to initiate use, the development of regular patterns of use, and
      (for some individuals) the subsequent development of problems associated with
      alcohol use. Using data from two population-based, longitudinal twin studies,
      FinnTwin16 (FT16) and FinnTwin12 (FT12), we applied multiple stage genetic models
      (Heath et al., Twin Res. 5 (2002) 113) to better understand the extent to which
      genetic and environmental influences impact the initiation of alcohol use,
      frequency of use in adolescence and young adulthood, and alcohol problems in
      young adulthood. Shared environmental factors played a large role in initiation,
      and a more moderate role on frequency of use, and it was largely the same
      influences acting across these stages of use. However, there was no significant
      evidence of shared environmental influences on alcohol problems in early
      adulthood. Problems were largely influenced by genetic factors that overlapped
      with genetic influences on frequency of use. Unique environmental factors were
      largely specific to each stage, with some overlap between alcohol problems and
      frequency of use at age 25.

PMID- 16586154
TI  - Brief report: A theory-of-mind-based social-cognition training program for school
      aged children with pervasive developmental disorders: an open study of its
      effectiveness.

PMID- 16586156
TI  - Ask the editor.

PMID- 16586155
TI  - Medicaid expenditures for children with autistic spectrum disorders: 1994 to
      1999.
AB  - This study used data from 1994 to 1999 from one large county in Pennsylvania to
      estimate the Medicaid expenditures of children diagnosed with autism spectrum
      disorders (ASD) and to compare these expenditures with those of other Medicaid
      eligible children. On average, children diagnosed with ASD had expenditures 10
      times those of other children. Differences in expenditures were driven in large
      part by inpatient psychiatric care. Further research is required to determine
      whether hospitalized children could be served in less restrictive and less
      expensive settings. Lack of differences in ambulatory care expenditures suggests
      that children with ASD are not receiving additional primary care services that
      would be indicative of appropriately coordinated services as suggested by the
      medical home model.

PMID- 16586157
TI  - The Autism-Spectrum Quotient (AQ) in Japan: A cross-cultural comparison.
AB  - The AQ (Autism-Spectrum Quotient) is a self-administered instrument for measuring
      the degree to which an adult with normal intelligence has the traits associated
      with the autistic spectrum. The AQ was administered in Japan to test whether the
      UK results would generalize to a very different culture. Three groups of
      subjects, adults with AS or HFA (n = 57), adult controls (n = 194), and
      University students (n = 1050) were assessed. The adults with AS/HFA had a mean
      AQ score which was significantly higher than both the controls and the University
      students. Among the controls, males scored significantly higher than females. The
      similarity of results in both the general population and the clinical group
      across the two cultures was remarkable.

PMID- 16586162
TI  - Peer coaching shows promise for residents as teachers.

PMID- 16586163
TI  - Research in family medicine.

PMID- 16586164
TI  - Documenting competency in the mini mental state exam.

PMID- 16586165
TI  - The "aha!" moment.

PMID- 16586166
TI  - "We must test the blood for antigens".

PMID- 16586167
TI  - Teaching the new competencies using the gap analysis approach.

PMID- 16586168
TI  - "Interacts well with patients".

PMID- 16586169
TI  - The wizard in you.

PMID- 16586170
TI  - The diverse functions of role models across primary care specialties.
AB  - BACKGROUND AND OBJECTIVES: This study investigated the relationship of role
      models to primary care specialty and gathered information on the attributes and
      functions of role models. METHODS: A questionnaire on medical school experiences
      and attitudes was administered to primary care graduates from 24 US medical
      schools. RESULTS: Questionnaires were completed by 1,457 physicians. Sixty-three
      percent of primary care respondents had a role model. Having a role model was
      significantly related to current specialty and ethnicity. Respondents most valued
      their role models' patient relationships. For family medicine and internal
      medicine graduates, having a role model was related to more contact and more
      positive views of faculty in their specialty. Those with a role model reported
      that primary care was encouraged at their medical school and were more satisfied
      with their specialty choice. CONCLUSIONS: Role models may be more important to
      students who are not well represented among medical school faculty, namely women,
      underrepresented ethnic minorities, and those interested in family medicine. For
      family medicine graduates, role models function to moderate negative stereotypes.
      Role models may also make explicit the values of physicians in that specialty,
      making students more informed when choosing a specialty and as a consequence more
      satisfied with the decision.

PMID- 16586171
TI  - Residents in trouble: an in-depth assessment of the 25-year experience of a
      single family medicine residency.
AB  - BACKGROUND AND OBJECTIVES: Graduate medical education program directors struggle
      with resident trainees who develop problems in academic and personal spheres
      leading to probation, resignation, or termination of training. These "residents
      in trouble" generate a disproportionate amount of work and can demoralize faculty
      and residents. Only two prior studies have identified the prevalence of residents
      in trouble. In both studies, the prevalence was based on nonvalidated program
      director self-report. In contrast, our study uses a review of primary data
      sources to describe the prevalence, types of problems, remediation methods, and
      outcomes for residents in trouble over the 25-year experience of a residency
      program. METHODS: Five primary data sources were reviewed for every trainee who
      was enrolled from 1978-2003 at the David Grant Medical Center Family Medicine
      Residency, looking for any of eight types of occurrences previously identified in
      the literature as marking a resident in trouble. RESULTS: Over this 25-year
      period, 230 residents entered training and 209 graduated. The prevalence of
      residents in trouble was 9.1%. The types of problems encountered included
      divorce, psychiatric illness, substance abuse, attitudinal problems,
      interpersonal conflict, excessive patient complaints, and insufficient knowledge.
      A variety of remediation approaches were used, and 90% of the residents in
      trouble graduated. CONCLUSIONS: The 9.1% provides a point of comparison for
      program directors to know if their residency has a disproportionate rate of
      problems requiring organizational reform or if they are dealing with the
      normative experience of a training program. Our program's experience supports
      five suggestions for the management of residents in trouble.

PMID- 16586172
TI  - A national survey of family medicine residency education in geriatric medicine:
      comparing findings in 2004 to 2001.
AB  - BACKGROUND AND OBJECTIVES: We compared findings from this 2004 survey with our
      2001 survey to determine progress in family medicine residency programs' efforts
      to better train residents to care for America's aging population. METHODS: A
      survey was mailed and made available on-line to all 470 family medicine residency
      directors in the United States. RESULTS: The response rate was 71%. Ninety-six
      percent of family medicine residencies have a required geriatrics curriculum,
      compared to 92% in 2001. There was a significant increase in the number of
      required lecture hours in geriatrics in 2004 as compared to 2001. Since 2001, the
      median number of MD geriatrics faculty per program has nearly doubled from .5
      full-time equivalent (FTE) to .9 FTE. Conflicting time demands with other
      curricula was ranked as the most significant barrier to geriatrics education in
      both 2004 and 2001. However, in 2001, the attitude of residents was listed as a
      significant barrier by 32.1% of the program directors as compared to just 3.6% in
      2004. CONCLUSIONS: Family medicine educators are continuing to improve the
      training of residents to provide state-of-the-art care for the aging population.
      Faculty must take advantage of this period of experimentation in residency
      education to identify best practices for geriatrics education.

PMID- 16586174
TI  - Implementation of curriculum by family medicine fellows: what factors help and
      what factors hinder?
AB  - BACKGROUND AND OBJECTIVES: The need for change in medical curricula is
      increasing, due partially to tougher curriculum and evaluation standards.
      Participants in our academic medicine fellowship learn to develop curricula, but
      not all are successful at fully implementing them. This study looked for
      facilitators of and barriers to curriculum implementation by individual fellows.
      A literature review uncovered studies identifying institutional variables
      relating to successful curriculum innovation but little that identified variables
      pertaining to the individual curriculum developer. METHODS: We interviewed alumni
      of the curriculum development track of the Primary Care Faculty Development
      Fellowship at Michigan State University, asking what promoted or hindered their
      curriculum implementation. We analyzed interview notes to identify themes
      according to a theoretical framework. RESULTS: Common facilitators were (1)
      having a strong advocate, (2) perception of need for the curriculum by both
      fellow and institution, and (3) having a curriculum plan. Common barriers were
      (1) no time slot for curriculum, (2) fellow had left job, and (3) curriculum was
      too large or complex. CONCLUSION: Successful curriculum developers have powerful
      advocates of well-designed curriculum plans that address recognized institutional
      needs.

PMID- 16586173
TI  - Health care disparities in postmenopausal women referred for DXA screening.
AB  - BACKGROUND: Racial disparities have been identified in a number of areas in
      clinical medicine. Limited data are available on osteoporosis screening rates
      between races. We assessed the racial distribution in Dual Energy X-ray
      Absorptiometry (DXA) screening rates among African American and Caucasian women
      referred from our primary care clinics. METHODS: We obtained DXA results during
      the years 1998-2002 for all 546 women ages >50 years referred for bone mineral
      density (BMD) testing from a primary care population. We compared the DXA
      screening rates between African American and Caucasian women with the racial
      demographics of the referring primary care clinic population. RESULTS: African
      American women represented 45.9% and Caucasian women 51.7% of our primary care
      clinic population. Yet, only 14.5% (n=79) of the DXA screened women were African
      American, while 82.8% (n=452) were Caucasian. Age and recognized risk factors
      only explained a small portion of this difference. In women 65 years and older
      with universal screening recommendations, 19.4% (n=46) of the screened women were
      African American, and 80.6% (n=191) were Caucasian. The prevalence of
      osteoporosis was similar in both populations, 21.5% and 20.1% for African
      American and Caucasian women, respectively. CONCLUSIONS: Significantly fewer
      African American women had BMD screening even though national guidelines do not
      differentiate by race. The large disparity between the proportion of African
      American and Caucasian women screened calls for more equitable BMD screening
      among races.

PMID- 16586176
TI  - Leaving rural practice.

PMID- 16586175
TI  - How well are practice management curricula preparing family medicine residents?
AB  - BACKGROUND: While emphasis has been placed on practice management curricula in
      residency, studies indicate that residents are not adequately prepared. To assess
      the effectiveness of current practice management skills training in residency, we
      examined the confidence levels of family medicine residents and recent graduates
      in practice management skills. METHODS: A survey was sent to family medicine
      residency programs within South Carolina. Participants ranked their confidence
      level in 13 practice management skills on a 5-point Likert scale. Analysis of
      covariance compared confidence levels in their skills while controlling for
      program, gender, and age. Residency directors of these programs were also
      surveyed about the content of their practice management programs. RESULTS:
      Residents and graduates rated their confidence in all areas moderately high.
      Graduates rated themselves significantly more confident than residents did in
      seven practice management skills. CONCLUSIONS: Family medicine practice
      management curricula appear to be effective in establishing confidence regarding
      practice management skills in residents and recent graduates.

PMID- 16586177
TI  - On being a young teacher-much to learn, much to teach.

PMID- 16586178
TI  - J.R.'s Choices.

PMID- 16586181
TI  - Breast cancer: The chronic disease.

PMID- 16586182
TI  - Improving quality of life for Department of Veterans Affairs nursing home
      residents through music and art.

PMID- 16586183
TI  - Prevalence and characteristics of chronic pain in veterans with spinal cord
      injury.
AB  - To assess prevalence and characteristics of individual chronic (>6 mo) pain
      components in the veteran spinal cord injury (SCI) population, we conducted a
      telephone survey with 348 (66%) of 530 veterans with SCI who received care from
      one regional Department of Veterans Affairs SCI center during a 3 yr period. The
      short-form McGill Pain Questionnaire was used to assess qualitative properties of
      the pain experience. Other questions were used to assess frequency, duration,
      intensity, exacerbating factors, and effects on daily activities. Of the
      participants, 75% reported at least one chronic pain component. The majority
      (83%) of the chronic pain components occurred daily (mean = 27.4 d/mo) and lasted
      most of the day (mean = 17.4 h/d). Mean pain intensity in the week before the
      interview averaged 6.7 (on a 0 to 10 scale), while worst pain intensity averaged
      8.6. Two-thirds (67%) of the chronic pain components interfered with daily
      activities. The most commonly selected pain descriptors were "aching," "sharp,"
      "hot-burning," and "tiring-exhausting." More research is needed to identify
      better ways to prevent, assess, and treat chronic pain in the veteran SCI
      population.

PMID- 16586184
TI  - Chronicity of pain associated with spinal cord injury: A longitudinal analysis.
AB  - This study determined the stability of self-reported clinical pain
      characteristics and pain-induced interference with sleep and daily activities in
      people with spinal cord injury. The study followed up a previous survey that
      identified clinical pain patterns (i.e., neuropathic pain below the level of
      injury; upper-limb pain in tetraplegia; and severe, persistent pain). A
      confirmatory factor analysis (CFA) of the present study's data confirmed the
      previously observed pain patterns. The CFA also confirmed positive correlations
      between the surveys on individual pain characteristics (i.e., number of pain
      locations [r = 0.63, p < 0.001], number of descriptors [r = 0.61, p < 0.001],
      pain intensity [r = 0.68, p < 0.001], and temporal aspects [r = 0.47, p <
      0.001]). Despite an overall stable clinical picture of pain, "aching" pain (p <
      0.001) and sleep interference caused by pain (p < 0.001) significantly increased
      over time.

PMID- 16586185
TI  - Video-capture virtual reality system for patients with paraplegic spinal cord
      injury.
AB  - This article presents results from a feasibility study of a video-capture virtual
      reality (VR) system used with patients who have paraplegic spinal cord injury
      (SCI) and who need balance training. The advantages of the VR system include
      providing the user with natural control of movements, the ability to use as many
      parts of the body as are deemed suitable within the context of therapeutic goals,
      and flexibility in the way the system can be adapted to suit specific therapeutic
      objectives. Thirteen participants with SCI experienced three virtual environments
      (VEs). Their responses to a Short Feedback Questionnaire showed high levels of
      presence. We compared performance in the environments with a group of 12
      nondisabled participants. Response times for the patient group were significantly
      higher and percentage of success was significantly lower than that for the
      nondisabled group. In addition, significant moderate correlations were found
      between performance within a VE and static balance ability as measured by the
      Functional Reach Test. This study is a first step toward future studies aimed at
      determining the potential of using this VR system during the rehabilitation of
      patients with SCI.

PMID- 16586186
TI  - Effects of vibratory stimulation on sexual response in women with spinal cord
      injury.
AB  - Women with spinal cord injuries (SCIs) have predictable alterations in sexual
      responses. They commonly have a decreased ability to achieve genital sexual
      arousal. This study determined whether the use of vibratory stimulation would
      result in increased genital arousal as measured by vaginal pulse amplitude in
      women with SCIs. Subjects included 46 women with SCIs and 11 nondisabled control
      subjects. Results revealed vibratory clitoral stimulation resulted in increased
      vaginal pulse amplitude as compared with manual clitoral stimulation in both SCI
      and nondisabled subjects; however, these differences were not statistically
      significant. Subjective levels of arousal were also compared between SCI and
      nondisabled control subjects. Both vibratory and manual clitoral stimulation
      resulted in significantly increased arousal levels in both groups of subjects;
      however, statistically significant differences between the two conditions were
      only noted in nondisabled subjects. Further studies of the effects of repetitive
      vibratory stimulation are underway.

PMID- 16586187
TI  - Heart rate as a predictor of energy expenditure in people with spinal cord
      injury.
AB  - This study evaluated the accuracy of heart rate calibrated from a maximum
      exercise test for predicting energy expenditure during five activities of daily
      living (ADL) in participants with spinal cord injury (SCI). Thirteen individuals
      with SCI underwent maximum exercise testing, followed by portable heart rate and
      metabolic testing during five ADL. A regression equation was developed from heart
      rate and oxygen uptake responses during the maximum exercise test for each
      subject. Based on this individualized equation, heart rate measured during the
      ADL was used to estimate energy expenditure for each participant. Predicted
      energy expenditure from heart rate was compared with that measured by indirect
      calorimetry with the use of oxygen uptake. Heart rate derived from the
      individualized regression equations explained 55% of the variance in measured
      energy expenditure, compared with only 8.3% from heart rate alone. However,
      calibrated heart rate consistently overestimated the actual kilocalories used; on
      average, the estimated energy expenditure was roughly 25% higher than that
      measured by oxygen uptake. Heart rate can be used as a gross estimate of energy
      expenditure during higher-intensity ADL in people with SCI when individual
      calibration of heart rate from maximum exercise testing is used.

PMID- 16586189
TI  - A multicriteria decision analysis of augmentative treatment of upper limbs in
      persons with tetraplegia.
AB  - This study supported the evaluation by a rehabilitation team of the performance
      of two treatment options that improve the arm-hand function in subjects with
      sixth cervical vertebra (C6) level Motor Group 2 tetraplegia. The analytic
      hierarchy process, a technique for multicriteria decision analysis, was used by a
      rehabilitation team and potential recipients to quantitatively compare a new
      technology, Functional Elec trical Stimulation (FES), with conventional surgery.
      Perform-ance was measured by functional improvement, treatment load, risks, user
      friendliness, and social outcomes. Functional improvement after FES was
      considered better than that after conventional surgery. However, the
      rehabilitation team's overall rating for conventional surgery was slightly higher
      than that for FES (57% vs 44%). Compared with the rehabilitation team, potential
      recipients gave greater weight to burden of treatment and less weight to
      functional improvement. This study shows that evaluation of new technology must
      be more comprehensive than the evaluation of functional improvement alone, and
      that patient preferences may differ from those of the rehabilitation team.

PMID- 16586188
TI  - Effect of a vitamin D analog on leg bone mineral density in patients with chronic
      spinal cord injury.
AB  - A randomized, placebo-controlled trial was performed to determine the effect of a
      vitamin D analog (1-alpha-hydroxyvitamin D(2) [1-alpha D(2)]) on the bone mineral
      density (BMD) in patients with chronic spinal cord injury (SCI). Forty subjects
      with chronic complete motor SCI were enrolled. The mean plus or minus standard
      deviation age and duration of injury were 42 plus or minus 12 yr and 11 plus or
      minus 10 yr, respectively. Either 4 micrograms 1-alpha D(2) (n = 19) or placebo
      (n = 21) was administered daily for 24 mo. Metabolic markers of bone resorption
      and formation were obtained. Regional lower-limb dual-energy x-ray absorptiometry
      was performed at baseline and at 6, 12, 18, and 24 mo. Leg BMD and percent change
      from baseline significantly increased at 6 (percent change only), 12, 18, and 24
      mo in the treatment group, but not in the placebo group. Urinary N-telopeptide, a
      marker of bone resorption, was significantly reduced during treatment with 1
      alpha D(2), but markers of bone formation were not changed.

PMID- 16586190
TI  - Efficacy of gabapentin in treating chronic phantom limb and residual limb pain.
AB  - Twenty-four adults with phantom limb pain (PLP) and/or residual limb pain (RLP)
      participated in a double-blind crossover trial. Participants were randomly
      assigned to receive gabapentin or placebo and later crossed over to the other
      treatment, with a 5-week washout interval in which they did not receive
      medication. Gabapentin was titrated from 300 mg to the maximum dose of 3,600 mg.
      Measures of pain intensity, pain interference, depression, life satisfaction, and
      functioning were collected throughout the study. Analyses revealed no significant
      group differences in pre- to posttreatment change scores on any of the outcome
      measures. More than half of the participants reported a meaningful decrease in
      pain during the gabapentin phase compared with about one-fifth who reported a
      meaningful decrease in pain during the placebo phase. In this trial, gabapentin
      did not substantially affect pain. More research on the efficacy of gabapentin to
      treat chronic PLP and RLP is needed.

PMID- 16586191
TI  - Colorimetric analysis of silicone cosmetic prostheses for upper-limb amputees.
AB  - Every year the Italian National Insurance Institute of Accidents on Work (INAIL)
      Prosthesis Centre manufactures more than 300 silicone cosmetic upper-limb
      prostheses that are aesthetically similar to patients' missing limbs; however,
      the prostheses have the following drawbacks: subjectivity in color choice, high
      production costs, and long time frames for patient tests and prosthesis
      production. In an attempt to minimize these factors, we performed a study to test
      various systems that automatically detect the color of human skin. Such a system
      would allow us to reproduce a patient's exact skin color for silicone cosmetic
      prostheses. We analyzed the color identification systems available on the market
      and assessed the possibility of introducing such a system into the production
      cycle of the prostheses. We found that because of intrinsic factors of the
      materials, automatic color detection for prosthesis production is complex.
      Therefore, any of the systems we tested will require further development for full
      satisfaction of the needs of prostheses manufacturers.

PMID- 16586192
TI  - Relationship between foot type, foot deformity, and ulcer occurrence in the high
      risk diabetic foot.
AB  - We hypothesized an association between foot type, foot deformity, and foot
      ulceration and conducted an analysis of a well-characterized, high-risk diabetic
      population of 398 subjects. The average age was 62 years of age and 74% of the
      study population were males. Foot-type distributions were 19.5% pes cavus (high
      arch), 51.5% neutrally aligned (normal arch), and 29.0% pes planus (low arch). We
      quantified the presence of hallux valgus (23.9%), hammer/claw toes (46.7%), and
      hallux limitus (24.4%). A significant association was found between foot type and
      hallux valgus (p = 0.003); pes planus feet had the highest prevalence as compared
      with neutrally aligned feet (odds ratio [OR] = 2.43, p = 0.0006). Foot type was
      also significantly associated with fixed hammer/claw toes (p = 0.01); pes cavus
      feet had the highest prevalence as compared with neutrally aligned feet (OR =
      3.89, p = 0.001). Foot type was also significantly associated with hallux limitus
      (p = 0.006) with pes planus feet having the highest prevalence as compared with
      neutrally aligned feet (OR = 2.19, p = 0.003). However, foot type was not
      significantly related to any ulcer outcome (p = 0.7). Fixed hammer/claw toes (OR
      = 3.91, p = 0.003) and hallux limitus (OR = 3.02, p = 0.006) were associated with
      increased risk of any ulcer occurrence. This study affirms that foot type and
      foot deformity are related and that foot deformities are associated with ulcer
      occurrence.

PMID- 16586193
TI  - Enhanced cognitive-behavioral therapy for vocational rehabilitation in
      schizophrenia: Effects on hope and work.
AB  - To address the effects of dysfunctional cognitions on vocational outcome of
      people with schizophrenia spectrum disorders, we developed the Indianapolis
      Vocational Intervention Program (IVIP), a cognitive-behavioral program of group
      and individual interventions. Fifty participants with schizophrenia or
      schizoaffective disorder were offered 6-month work placements and randomized to
      receive IVIP (n = 25) or standard support services (n = 25). Hours worked were
      measured weekly, and work performance was assessed biweekly with the use of the
      Work Behavior Inventory. Hope and self-esteem were assessed at baseline and at 5
      months with the Beck Hopelessness Scale and the Rosenberg Self-Esteem Schedule.
      Analysis of variance (ANOVA) revealed that the IVIP group worked significantly
      more weeks and had better average work performance than the standard support
      group. Repeated measures ANOVA of baseline and follow-up scores indicated that
      the IVIP group sustained baseline levels of hope and self-esteem through follow
      up, while the standard support group experienced declines. Results provide
      initial evidence of the effectiveness of the IVIP.

PMID- 16586194
TI  - Short-duration robotic therapy in stroke patients with severe upper-limb motor
      impairment.
AB  - Chronic motor deficits in the upper limb (UL) are a major contributor to
      disability following stroke. This study investigated the effect of short-duration
      robot-assisted therapy on motor impairment, as measured by clinical scales and
      robot-derived performance measures in patients with chronic, severe UL
      impairments after stroke. As part of a larger study, 15 individuals with chronic,
      severe UL paresis (Fugl-Meyer < 15) after stroke (minimum 6 mo postonset)
      performed 18 sessions of robot-assisted UL rehabilitation that consisted of goal
      directed planar reaching tasks over a period of 3 weeks. Outcome measures
      included the Fugl-Meyer Assessment, the Motor Power Assessment, the Wolf Motor
      Function Test, the Stroke Impact Scale, and five robot-derived measures that
      reflect motor control (aiming error, mean speed, peak speed, mean:peak speed
      ratio, and movement duration). Robot-assisted training produced statistically
      significant improvements from baseline to posttreatment in the Fugl-Meyer and
      Motor Power Assessment scores and the quality of motion (quantified by a
      reduction in aiming error and movement duration with an increase in mean speed
      and mean:peak speed ratio). Our findings indicate that robot-assisted UL
      rehabilitation can reduce UL impairment and improve motor control in patients
      with severe UL paresis from chronic stroke.

PMID- 16586195
TI  - Use of the Delphi Technique for developing national clinical guidelines for
      prescription of lower-limb prostheses.
AB  - The aim of this project was the development of evidence- and consensus-based
      clinical practice guidelines for lower-limb prosthesis prescription for achieving
      transparency and consensus among clinicians, manufacturers, and insurance
      companies. This article describes a modified Delphi Technique, which is based on
      different methods of collecting evidence, and its role in the development of
      national clinical guidelines for prosthesis prescription. We used a multimethod
      approach to develop guidelines for the clinical practice of prosthesis
      prescription for lower-limb amputees. The Delphi Technique was central in the
      process, and the panel was made up of experts from three key disciplines on a
      national level. Our approach involved various methods: a systematic review, a
      survey of national clinical practice on prosthesis prescription, and interviews
      with experts. These activities resulted in 45 postulates about prosthesis
      prescription. The views of the national expert panel were then presented at a
      consensus development conference. The participants in the Delphi Technique
      sessions reached a consensus on 37 of the postulates on prosthesis prescription
      for lower-limb amputees. The postulates were categorized according to amputation
      level and partitioned into different domains. The total process resulted in the
      development of draft clinical guidelines comprising guidance for prescribing
      prostheses for the lower limb. The scope and applicability of these guidelines
      will have to be measured and evaluated in future work.

PMID- 16586201
TI  - [Definitions of respiratory failure].

PMID- 16586196
TI  - An initial study on lip perception of electrotactile array stimulation.
AB  - We conducted an initial study on tactile sensory characteristics of the lips by
      applying electrotactile array stimulation on the center surfaces of the upper and
      lower lips. We performed experiments of threshold measurement and rating of two
      line separation to evaluate the tactile sensitivity and spatial discriminating
      ability of the lips, respectively. Three stimulator arrays of different sizes
      presented electrotactile patterns on the lips of eight subjects (six male, two
      female) to measure the electrotactile performance in relation to stimulator size
      and spacing. Experimental results showed that the lips required very low
      intensities for effective electrotactile stimulation. As the stimulator diameter
      increased from 75 micrometers to 1.55 millimeters, the average stimulation
      intensity at the threshold level decreased from 12.5 to 6.3 V for the lower lip
      and from 13.3 to 7.1 V for the upper lip. Meanwhile, the two-line separation
      rating experiment showed that both upper and lower lips possessed high spatial
      discriminating ability. The average percentages of correct rating of two adjacent
      lines ranged from 80.5% to 88.2% on the two stimulator arrays with center-to
      center spacing of at least 2.40 mm. In addition, sensitivity analysis indicated
      that the upper lip slightly outperformed the lower lip in spatial discrimination.

PMID- 16586202
TI  - [Six-minute-walking-test with and without oxygen in patients with COPD:
      comparison of walking distance and oxygen saturation in varying forms of
      application].
AB  - BACKGROUND: Patients afflicted with COPD and respiratory Failure often experience
      a decrease of oxygen saturation (SaO (2)) under physical strain. The aim of our
      study was to find out which changes occur in walking distance and SaO (2) under
      the application of Oxygen (O (2)) 2 l/min continous flow, under demand (D) and
      under normal air (RL) when performing the Six-Minute-Walking-Test (6MWT) and
      further, in which way do the 10 patients of the shortest walking distance group
      (group I) differ from the eo patients with the longest walking distance (group
      II) concerning the starter 6 MWT (under CF). METHOD AND PATIENTS: 27 patients
      undertook a 6MWT three days in a row with CF, D and (RL), 6 minutes before (phase
      I), during (phase II) and after (phase III) the 6MWT oxygen was applied in CF
      (day I), D (day II) and RL (day III), the mean oxygen saturation in each phase
      was measured and the change (DeltaSaO (2)) during and after the 6MWT was
      calculated. Additionally we measured the DeltaSaO (2) between start and middle,
      as well as between middle and end of each phase. In close proximity to the tests
      FEV (1) and pO (2) was determined. RESULTS: In the total of all test persons
      there was no significant difference in the walking distance tetween the 3 forms
      of application. There was, however, a highly significant decrease of the oxygen
      saturation. The decrease in the two forms of oxygen application did not differ
      significantly. The decrease of SaO (2) under strain and the consecutive rise
      under rest occurred within the first 3 minutes of each phase. Patients of group
      II were often able to increase their walking distance under RL, whereas patients
      of group I decreased their walking distance further. In group II FEV (1) abs. was
      significantly higher, but FEV (1) % debit and pO (2) did not differ significantly
      between both groups. CONCLUSIONS: Patients with a long walking distance showed a
      marked learning effect even under RL, they presented a higher FEV (1), but not an
      increased pO (2). The phase of resaturation after the end of strain is short.
      Oxygen application through a demand valve with a flow rate of 2 l/min is not
      inferior to a continuous flow. In more than half of all patients the SaO (2) fell
      below 90 % under both forms of oxygen application, in conclusion the flow rate
      should be increased in these cases.

PMID- 16586203
TI  - [The angiofollicular lymph node hyperplasia Castleman--casuistic and review of
      the literature].
AB  - The Castleman Disease, also known as angiofollicular lymph node hyperplasia is a
      rare disorder that results in abnormal proliferation of B-lymphocytes and plasma
      cells in lymphoid organs. It was first described as a pathologic entity in 1954
      and later defined by Castleman et al. in 1956. The Castleman's disease is
      characterised by lymph node hyperplasia with vascular proliferation and
      endothelial hyperplasia. On the basis of histologic criteria it has been divided
      into hyaline-vascular and plasma cell variant. The hyaline-vascular type (90 % of
      cases), generally benign, occurs in younger patients with a localised mediastinal
      mass - surgical excision is curative. The plasma cell variant (10 % of cases),
      localised or multicentric, is generally aggressive, and occurs in older patients
      with generalised lymphadenopathy, hepatosplenomegaly, systemic symptoms, anaemia,
      elevated inflammatory indices, and a polyclonal rise in immunoglobulins. The
      prognosis is poor despite the Chemotherapy. Surgery is not indicated. We present
      two cases of unicentric Castleman Tumor of hyaline-vascular type. The patients
      were cured by surgical resection.

PMID- 16586204
TI  - [Silicosis or chronical obstructive bronchitis/emphysema as compensatory
      occupational disease].
AB  - We report on a 73-year-old man, who developed chronical bronchitis after 15 years
      of working as a coal miner. About 3 decades later a manifest COPD, and
      additionally a silicosis, were diagnosed. The silicosis was rated as an accepted
      case for the hazard insurance, but not as a reason for pension. The reasoning for
      the declining of pension for the applicant is refuted by the literature which
      defines occupational diseases and is generally accepted by the legislation. In
      this case the insurance argued that in low- to medium-grade spread of silicosis
      functional deficits of the lung and/or the cardio-vascular system are not to be
      expected. Thus the recognition and recompensation of a BK 4101 (grinders'
      disease, silicosis) was proposed, in contrast to the social court which demanded
      an expert's opinion on causality.

PMID- 16586205
TI  - [Efficacy and safety of sublingual immunotherapy--a detailed analysis].
AB  - Sublingual immunotherapy (SLIT) was developed to avoid the risk of severe
      systemic side effects which occur in subcutaneous immunotherapy. Data from more
      than 20 controlled studies clearly show the efficacy and safety of this type of
      immunotherapy in patients with allergic rhino-conjunctivitis due to pollen and
      mites. The data for allergic asthma still need confirmation. Sublingual
      immunotherapy is no substitute for subcutaneous immunotherapy but an additional
      option for defined groups of patients. The application of a sufficient amount of
      allergen is important for the efficacy of SLIT. According to the recommendation
      of the ARIA working group, a 50- to 100-fold cumulative dose should be applied as
      compared to subcutaneous immunotherapy. SLIT can be used preseasonally, during
      the saison or perennially. Therapy starts with a daily increase of the dose. In
      some cases, e. g., in adult patients with pollen allergy, doses can be increased
      within hours. The well-tolerated maintenance dose should be taken three times a
      week or daily. The sublingual seasonal short-time immunotherapy may become an
      additional option for subgroups of patients, e. g., for adolescents.

PMID- 16586207
TI  - [Curriculum Pneumologicum 2005. Part 4].

PMID- 16586206
TI  - [Principles and function of mechanical ventilation: classification and modes of
      ventilators].
AB  - A spectrum of diseases is associated with the necessity for partial or total
      support of pulmonary ventilation. The insight into the function of ventilators
      and their modes reduces the spectrum of ventilatory support to a few basic
      principles. The knowledge enables the pulmonary intensivist to adapt mechanical
      ventilation to the individual patient's needs. This overview describes the
      technical aspects of mechanical ventilation and summarizes the variety of
      specific modes implied.

PMID- 16586227
TI  - Safety and success of vaginal birth after cesarean delivery in patients with
      preeclampsia.
AB  - The objective of this study was to determine if preeclampsia (PRE) or gestational
      hypertension (GH) affects the rate of success of vaginal birth after cesarean
      delivery (VBAC), VBAC-related complications, or patient election to attempt VBAC.
      We performed a retrospective cohort study of all women who were offered VBAC from
      1996 to 2000 in 17 community and university hospitals. Demographic, medical, and
      obstetric history, complications, treatment, and index pregnancy outcome
      information was collected on all patients in the database. Bivariate analysis and
      multivariable logistic regression were used to assess the independent association
      between GH and PRE and the rate of success of VBAC, VBAC-related complications,
      or patient election to attempt VBAC. A total of 25,005 patients were registered
      in the database. 13,706 (54.81%) attempted VBAC and 11,299 (45.19%) elected
      repeat cesarean delivery. After adjusting for confounding variables using
      multivariable logistic regression, patients with PRE were more likely to fail
      VBAC (relative risk [RR], 1.56; 95% CI, 1.22 to 2.00). Patients with GH were less
      likely to attempt VBAC (RR, 0.39; 95% CI, 0.34 to 0.46). A total of 304 (1.46%)
      patients had a uterine rupture. The VBAC group had a rupture rate of 0.93% and
      the elective cesarean group had a rupture rate of 0.04%. There was no difference
      in uterine rupture rates between the cohorts. Patients with gestational
      hypertension were less likely to attempt a VBAC. Patients with PRE, if they
      attempted a VBAC trial, had a higher VBAC failure rate. Patients with PRE or GH
      do not have increased uterine rupture rates. These findings can be used to
      improve mode of delivery counseling for VBAC candidate patients with
      preeclampsia.

PMID- 16586228
TI  - Profile of serum S100beta levels during maturation in fetal and neonatal sheep.
AB  - Serum levels of the protein S-100beta are dependent on three factors: rate of
      production, permeability of the blood-brain barrier, and rate of clearance. In
      the developing fetus and neonate all of these factors change at different rates.
      This study was performed to determine how serum S-100 levels varied during fetal
      and early postnatal life. Blood samples were obtained from 41 fetal and neonatal
      lambs. The blood was separated in a centrifuge and the serum drawn off and
      assayed for S-100beta using a commercially available radioimunoassay kit. S
      100beta did not appear in the blood until halfway through pregnancy. Thereafter,
      levels steadily increased until 1 month after birth. Following this, S-100beta
      levels decreased progressively until by 1 year of age, they had reached a
      plateau. S-100beta levels change significantly with normal fetal and neonatal
      maturation. Valid interpretation of other data from subjects of similar
      developmental stage must take into consideration this physiological variation.

PMID- 16586229
TI  - Prevalence of new maternal alloantibodies after intrauterine transfusion for
      severe Rhesus disease.
AB  - Limited information is published on the frequency of new maternal alloantibodies
      found in patients treated for isoimmunization. The purpose of this study was to
      determine the prevalence of additional maternal red cell alloantibodies, found
      after the initiation of treatment for Rhesus (Rh) disease. A retrospective review
      of all patients treated for severe Rh disease was undertaken. Rh disease
      requiring intrauterine blood transfusion was defined as severe. Gravidas with
      alloantibodies in addition to Rh were included, but those without Rh antibodies
      were excluded. New alloantibodies were defined as antibodies absent in previous
      pregnancies and on initial pregnancy screening, and found after the onset of
      invasive treatment. There were a total of 84 intrauterine blood transfusions
      performed in 31 gravidas with severe Rh disease. Seven patients (23%) were found
      to develop additional red cell alloantibodies after treatment during the
      pregnancy. Induction of additional maternal red cell alloantibodies after
      treatment for severe Rh disease is relatively common. This may have significant
      implications for future pregnancies in this high-risk population.

PMID- 16586230
TI  - Acute onset of severe hemolysis, elevated liver enzymes, and low platelet count
      syndrome in a patient with a partial hydatidiform mole at 17 weeks gestation.
AB  - Preeclampsia is uncommon prior to 24 weeks gestation and has been associated with
      partial and complete hydatidiform moles. We present an unusual case in which a
      patient was diagnosed with preeclampsia at 17 weeks gestation. Ultrasound
      findings were consistent with a partial hydatidiform mole. Within 24 hours of the
      onset of symptoms, the patient developed severe hemolysis, elevated liver
      enzymes, and low platelet count syndrome, with a platelet count of 20 x 10 (9)
      cells/L. Termination of pregnancy was performed with rapid resolution of signs,
      symptoms, and laboratory abnormalities. Triploid 69,XXY was confirmed at
      karyotype analysis. This case demonstrates the acuteness in which life
      threatening maternal conditions can arise with this uncommon complication of
      pregnancy, and the importance of correct identification of the characteristic
      ultrasonographic findings associated with a partial hydatidiform mole.

PMID- 16586231
TI  - Clinical concepts of futility and ethically justified limits on neonatal care: a
      case presentation of an infant with Apgar scores of 0 at 1, 5, and 10 minutes.
AB  - Appropriate length of delivery room resuscitative efforts for infants born
      without signs of life is controversial. We present the case of a preterm infant
      with Apgar scores of 0 at 1, 5, and 10 minutes but with a recovered heartbeat at
      15 minutes. Using the clinically relevant conceptions of the principle of
      futility, we examine the ethical justification for the successive decisions to
      initiate, continue, and ultimately limit care for this patient. This difficult
      case highlights the importance of understanding the ethical justification for
      clinical interventions that are made in the neonatal intensive care unit.

PMID- 16586232
TI  - Congenital cerebellar primitive neuroectodermal tumor in a newborn.
AB  - Neonatal primitive neuroectodermal tumor is a rare clinical entity. The initial
      presentation in affected newborns is often subtle, nonspecific, and rarely
      includes neurological signs. Here we report a newborn with congenital cerebellar
      primitive neuroectodermal tumor. We had detected hydrocephalus and enlarged
      biparietal diameter at the 36th week of gestational age by fetal ultrasonography.

PMID- 16586233
TI  - Persistent right umbilical vein associated with complex congenital cardiac
      malformation.
AB  - Umbilical venous catheterization is frequently used for vascular access during
      neonatal resuscitation. The differentiation between umbilical artery and vein,
      specifically during the resuscitation procedure, is clinically neither always
      easy nor unambiguous. A preterm infant of 35 weeks of gestational age was born
      after an uneventful course of his mother's pregnancy. Severe postnatal cyanosis
      led to the placement of presumed arterial and venous umbilical catheters. Chest x
      ray was suggestive of the presence of a persistent right umbilical vein (PRUV).
      Echocardiography showed a double outlet right ventricle with mitral atresia and a
      levo-atrial cardinal vein draining the left atrium into the azygos vein. The
      foramen ovale was firmly closed and conventional balloon atrioseptostomy failed.
      Several attempts of transseptal puncture and subsequent creation of an atrial
      septal defect were unsuccessful and the infant eventually died. There is an
      association of PRUV and congenital cardiac malformation. PRUV can be diagnosed
      prenatally if specifically looked for. The presence of PRUV can be the only clue
      prenatally alerting to the presence of congenital heart disease. Postnatal
      diagnosis of PRUV may justify echocardiography and cardiologic assessment even in
      the absence of clinical cyanosis.

PMID- 16586234
TI  - Risk of third-trimester amniocentesis: a case-control study.
AB  - Risks of third-trimester amniocentesis are considered minimal; however, only case
      series have been reported. We performed a case-control study in which women
      undergoing third-trimester amniocentesis were matched with controls undergoing
      antenatal testing for similar indications to determine adverse outcomes
      associated with the procedure. Cases undergoing amniocentesis at > 32 weeks for
      fetal lung maturity assessment followed by antepartum testing with nonstress test
      and amniotic fluid index determination were matched with controls undergoing only
      antepartum testing based on gestational age at testing and maternal age. The main
      outcome variable was a composite occurrence of obstetric complications within 48
      hours of testing, including urgent delivery, placental abruption, premature
      rupture of membranes (PROM), perinatal death, or Apgar score at 5 minutes < 7.
      Statistical analysis included Fisher's exact test and Student T-test, with P <
      0.05 considered significant. A total of 167 matched pairs of patients fulfilled
      the study criteria. Indications for both amniocentesis and antepartum testing,
      which included diabetes, preterm labor, and cholestasis, were similar in the two
      groups. As expected, gestational age at sampling/testing (36.4 +/- 1.4 [mean +/-
      standard deviation] versus 36.6 +/- 1.7 weeks; P = 0.2) and maternal age (31.4 +/
      5.8 versus 31.5 +/- 6.3 years; P = 0.9) were not different between cases and
      controls. The rate of the main outcome variable within 48 hours of testing was 0
      of 167 among cases and 1 of 167 among controls. Amniocentesis in the third
      trimester is not associated with increased risk of urgent delivery, placental
      abruption, PROM, Apgar score at 5 minutes < 7, or perinatal death within 48 hours
      of the procedure.

PMID- 16586235
TI  - Do serum beta-human chorionic gonadotropin levels on day 4 following methotrexate
      treatment of patients with ectopic pregnancy predict successful single-dose
      therapy?
AB  - The purpose of this study is to assess whether serum beta-human chorionic
      gonadotropin (beta-hCG) levels on day 4 following methotrexate (MTX) treatment in
      patients with ectopic pregnancy predict successful single-dose therapy or the
      need for subsequent surgical intervention. Retrospective analysis of patients
      with ectopic pregnancies treated with MTX (50 mg/m (2)) was conducted. Inclusion
      criteria for MTX management were serum beta-hCG < 15,000 mU/mL, absent fetal
      cardiac activity, ultrasonographic gestational sac < 3.5 cm, normal liver
      function tests, hemodynamically stable patient with no evidence of
      hemoperitoneum, and informed consent. Day 1, 4, and 7 serum beta-hCG levels were
      obtained. Outcome parameters included successful single-dose MTX management, the
      requirement for multiple treatments, and whether subsequent surgery was required.
      Receiver operator characteristic (ROC) curves were used. P < 0.05 was considered
      significant throughout. Eighty-three patients were studied. Of these, 60 patients
      were treated successfully with single doses, 16 patients required two doses, and
      two patients required three doses of MTX, and five underwent surgical management.
      Mean day 1 serum beta-hCG levels of patients successfully treated with single
      dose MTX was 3938.5 (+/- 589.2 [standard deviation]) versus 1767.65 (+/- 1237.8)
      mU/mL in patients requiring multiple doses of MTX therapy, ( P < 0.0001). ROC
      curves for serum beta-hCG levels on days 1, 4, and 7 were 0.449, 0.592, and
      0.754, respectively, indicating that only day 7 serum beta-hCG levels were
      associated with successful single-dose MTX therapy. Serum beta-hCG levels on day
      4 of MTX in patients with ectopic pregnancy do not predict successful single-dose
      therapy or the need for surgery.

PMID- 16586236
TI  - Adams-Oliver syndrome associated with cutis marmorata telangiectatica congenita
      and congenital cataract: a case report.
AB  - A female infant presented with Adams-Oliver syndrome (AOS), intrauterine growth
      retardation, severe cutis marmorata telangiectatica congenita, bilateral
      congenital cataract, and periventricular lesions. The here-reported association
      of bilateral congenital cataract with AOS is original. Adams-Oliver syndrome is a
      genetic defect that causes a vasculopathy and leads to a variety of phenotypes.
      This observation further supports the current understanding of the
      physiopathology of AOS.

PMID- 16586237
TI  - Comparison of cervical volume and cervical length to predict preterm delivery by
      transvaginal ultrasound.
AB  - The objective of this study was to evaluate predictive value of cervical volume
      and length measurement for preterm delivery in low-risk pregnancies by
      transvaginal ultrasound. Two hundred fifty pregnant women were underwent
      ultrasound examination at 22 weeks of gestation by transvaginal route. Cervical
      length, width, and anteroposterior diameters were measured and cervical volume
      was calculated. All subjects were observed until term. Predictive values of
      cervical length and cervical volume were calculated and compared with predict
      preterm delivery. Preterm delivery occurred in 18 patients (7.2%). Mean cervical
      length and volume were statistically different between term and preterm delivered
      patients ( P = 0.001). Areas under curves were 0.913 for cervical volume and
      0.923 for cervical length; this difference was not statistically significant ( P
      = 0.289). Sensitivity of cervical volume was 73.3% for 32-mL cut-off value with
      12.85% false-positive rate and cervical length had 80% sensitivity at the 33.15
      mm cut-off value with 12.7% false-positive rate. Cervical volume measurement by
      two-dimensional ultrasound did not add any benefit compared with the cervical
      length measurement for prediction of preterm delivery.

PMID- 16586238
TI  - Sudden fetal death associated with both duodenal atresia and umbilical cord
      ulcer: a case report and review.
AB  - We encountered one case of duodenal atresia complicated by massive intrauterine
      hemorrhage due to the perforation of an umbilical cord ulceration (UCU). UCU is
      an extremely rare complication in the perinatal period. Although the prenatal
      diagnosis of upper intestinal atresia has been established, little is known about
      the association between UCU and upper intestinal atresia. In this article, we
      report our case, review past articles, and discuss the underlying
      pathophysiological mechanisms of the cause of an UCU. Given the characteristic
      sites of upper intestinal atresia, we speculate that regurgitation of gastric or
      intestinal juice into the amniotic fluid could be responsible for the development
      of UCU. We also believe that close observation is required for patients who have
      upper intestinal atresia.

PMID- 16586240
TI  - Flexible sigmoidoscopy performed by nurses.
AB  - Flexible sigmoidoscopy by nurses has rapidly become a widely accepted technique
      for distal colonic investigation. This review explores the issues of training and
      application of nurse performed flexible sigmoidoscopy, including the limitations,
      complications and cost issues.

PMID- 16586239
TI  - Mitomycin C: an alternative conservative treatment for refractory esophageal
      stricture in children?
AB  - BACKGROUND AND STUDY AIMS: Mitomycin C is an antiproliferative agent that has
      been used successfully as an adjunct treatment in ophthalmological procedures, in
      the management of laryngeal and tracheal stenosis, and more recently to prevent
      the recurrence of caustic esophageal strictures in children. The aim of this
      study was to assess the efficacy and safety of local application of mitomycin C
      to refractory esophageal strictures in children. PATIENTS AND METHODS: We
      performed a preliminary prospective study of local application of mitomycin C in
      four children, aged between 1 year and 6 years, who had refractory esophageal
      strictures. Two of the children presented with strictures caused by caustic
      ingestion and the other two children had anastomotic strictures following
      surgical repair of congenital esophageal atresia. The patients had required
      between four and ten esophageal dilations over a 5-24-month period before
      mitomycin C application. After an endoscopic dilation, mitomycin C was applied
      onto the dilation wound using a rigid endoscope. RESULTS: No complications were
      observed after the procedure. One child required a second application of
      mitomycin C 2 weeks after the first application because of recurrence of
      dysphagia. All the children remained asymptomatic and none of them required
      further dilation over a mean follow-up period of 24 months. Radiological control
      examinations revealed that there was no recurrence of the esophageal strictures
      and esophageal biopsies performed during follow-up showed no signs of dysplasia.
      CONCLUSIONS: Local application of mitomycin C is a potential alternative to
      iterative dilations, surgery, or stent placement for the treatment of refractory
      esophageal strictures in children. However, prospective, long-term assessment of
      outcomes is needed before any definitive conclusion can be drawn about the
      usefulness of mitomycin C in these patients.

PMID- 16586241
TI  - Biliary metal stents and air embolism: a note of caution.
AB  - Metal stents are a valuable treatment modality for patients with biliary
      obstruction. However, we present here two patients whose cases may serve as a
      warning about an unusual complication associated with these stents. We
      encountered this complication after endoscopic retrograde cholangiography for
      obstructed metal biliary stents. The first patient, an 87-year-old man with a
      benign biliary stricture, failed to regain consciousness after clearing of his
      stent using a Dormia basket and balloon catheter. Cerebral air embolism was
      diagnosed on cerebral computed tomography, and transesophageal echocardiography
      revealed a patent foramen ovale as a precipitating factor for paradoxical air
      embolism. He survived and was discharged with a residual hemiparesis. In the
      second patient, a 54-year-old man who had a history of a Billroth II operation
      and chronic pancreatitis and who had a portal cavernoma with biliary obstruction
      due to collateral veins, electromechanical dissociation complicated the balloon
      catheter stent revision. Echocardiography performed during cardiopulmonary
      resuscitation showed major air embolism to the right heart. The patient died.
      These cases demonstrate that air may gain access to the venous system during
      therapeutic endoscopic procedures of this type. It is likely that the large
      diameter of metal stents and the potential for these stents to lacerate venous
      structures facilitate the entry of air into the venous circulation, an event
      which may have life-threatening consequences.

PMID- 16586242
TI  - Endoscopic management of persistent biliary leakage resulting from complete
      transection of the bile duct at cholecystectomy.
AB  - BACKGROUND AND STUDY AIMS: Injuries to the bile duct are not uncommon during
      cholecystectomy. While minor injuries are amenable to endoscopic therapy, major
      ones, such as complete transection of the duct, require surgical intervention. We
      report on the endoscopic management of such injuries. PATIENTS AND METHODS: We
      included in the study ten patients who had persistent postoperative bile drainage
      (either through a surgically placed catheter or through a biliocutaneous fistula)
      after their cholecystectomy procedure had been complicated by complete
      transection of the bile duct. Plastic biliary endoprostheses were placed in the
      bilioma through the papilla of Vater. In one patient, both the right and the left
      hepatic ducts were opacified by injecting contrast material through the drainage
      catheter and it was possible to place stents in both the ducts. RESULTS: All the
      patients improved clinically after the procedure. In one patient the stent became
      dislodged and an elective Roux-en-Y hepaticojejunostomy was performed, but it was
      possible to remove the stents from all the other patients. Two patients were
      referred for surgery but in both cases the bile flow through the bile duct was
      shown to be so good on nuclear imaging that they were not operated on. All the
      non-operated patients are well after a mean +/- SD follow-up of 22.3 +/- 5.5
      months. CONCLUSIONS: Placement of biliary stents in the bilioma is a useful
      adjunct to percutaneous drainage in patients with complete transection of the
      bile duct. After placement of a biliary stent in the bilioma the percutaneous
      drainage catheter may be removed. In one of our study patients it was also
      possible to place stents in the intrahepatic ducts and the bile duct was
      reconstructed. Long-term follow-up of these patients and further studies are
      required to assess the role of endoscopic management as an alternative to surgery
      in patients with this condition.

PMID- 16586243
TI  - Intestinal necrosis as a complication of epinephrine injection therapy during
      double-balloon enteroscopy.

PMID- 16586245
TI  - Fine-needle aspiration of peritumoral lymph nodes in esophageal cancer with
      endobronchial ultrasound.

PMID- 16586244
TI  - Endoscopic ultrasound diagnosis of Liesegang rings.

PMID- 16586246
TI  - Balantidiasis in a patient with suspected Crohn's disease.

PMID- 16586247
TI  - Nasal fossa hemorrhage mimicking a post-endoscopic sphincterotomy bleed.

PMID- 16586248
TI  - Esophageal intramural pseudodiverticulosis with symptomatic stricture:
      mediastinitis and papillomatosis as a complication of endoscopic intervention.

PMID- 16586249
TI  - Guidelines of the French Society for Digestive Endoscopy (SFED).

PMID- 16586250
TI  - Intussusception of the appendix resected at colonoscopy.

PMID- 16586251
TI  - Formation of an aortic graft-enteric fistula 20 years after aortic graft
      placement.

PMID- 16586252
TI  - Endoscopic management of pancreaticopleural fistulas: a report of three patients.
AB  - Pancreaticopleural fistulas are a rare complication of acute or chronic
      pancreatitis, and are usually treated by surgery. We report three patients whose
      pancreaticopleural fistulas were successfully treated by endoscopic retrograde
      cholangiopancreatography and drainage (stenting, nasopancreatic drainage). In one
      patient a pancreatic pseudocyst persisted despite successful initial closure of
      the leak using this method and, as it was also suspected to be infected,
      additional drainage of the pseudocyst was required. Endotherapy of
      pancreaticopleural fistulas could obviate the need for surgery when conventional
      medical treatment has failed in this condition.

PMID- 16586253
TI  - [The concept of working memory in schizophrenia: current evidence and future
      perspectives].
AB  - Working memory (WM) deficits are core symptoms of cognitive impairment in
      schizophrenia. The psychological concept of WM offers a theoretical and empirical
      framework for the investigation of perceptual and attentional dysfunction as well
      as of deficits of higher cognitive functions in schizophrenia. From a theoretical
      perspective, schizophrenic psychopathology and cognitive dysfunction can be both
      integrated and experimentally validated within the concept of WM-impairment. In
      the last years investigation of WM has been a major issue in neuropsychiatric
      research, not least because of the association of prefrontal cortex and WM
      function. The advent of functional imaging techniques, e. g. functional magnetic
      resonance imaging (fmri) has additionally contributed in generating
      neurobiological WM-models. Regarding the neuronal basis of WM-deficits in
      schizophrenia, prefrontal cortex dysfunction has been of major interest. This
      review provides a short overview on the concept of WM and its relevance for
      cognitive psychology, discussing both recent behavioral and functional
      neuroimaging evidence on WM-dysfunction in schizophrenia.

PMID- 16586254
TI  - [Recurrent depressive disorder in Caspar David Friedrich. A pathographical
      approach with operationalized diagnosis].
AB  - Caspar David Friedrich (1774 - 1840) is one of the most important German Romantic
      painters. In his paintings, he prototypically represents the melancholy, which
      has been mentioned by his contemporaries and later biographers. Art scientists
      have also referred to his melancholy for the interpretation of his work. From a
      medical point of view, there are only two pathographies which remain
      inconclusive. Having applied diagnostic criteria for psychiatric disorders to his
      letters and publications, to statements of his contemporaries and to his art, we
      propose that he had suffered from a recurrent major depression which occurred in
      1799 for the first time. At least three depressive episodes followed before he
      was struck by a stroke in 1835. There are epidemiological, psychodynamic and
      personality-typological reasons supporting our diagnostic assumption. The course
      of his depression corresponds to phases of reduced creativity, to the chosen
      techniques and motives. Finally we discuss the implications of our approach for
      the pathographical method in general.

PMID- 16586255
TI  - [Substance-induced disorders: moving towards DSM-V and ICD-11].
AB  - The development of substance abuse disorders (SUD) for DSM-V is put into
      perspective according to an expert meeting organized by APA and chaired by M.A.
      Schuckit and J.B. Saunders. Substantial compatibility with ICD-11 of WHO was
      expected to be achieved. A dependence syndrome, a non-dependence category as well
      as a subthreshold condition is supposed to be included in the SUD section in DSM
      V. Categorical criteria will possibly be supplemented by dimensions
      conceptualized as quantitative formulations of criteria content. General and
      substance-specific criteria may be included for dependence. The comorbidity
      problem requires more research to separate substance-induced from substance
      independent mental disorders in patients with SUDs. It was an open discussion,
      whether the aim to include biological criteria for better defining of SUDs will
      be achieved in DSM-V.

PMID- 16586256
TI  - [Felix Mendelssohn Bartholdy (1809 - 1847): the mystery of his early death].
AB  - Composer and director of music at Leipzig's Gewandhaus Felix Mendelssohn
      Bartholdy died remarkably young, on 4 November 1847, at the age of 38. The cause
      of his early death has been a mystery ever since. Three contemporary doctors
      diagnosed Nervenschlag ("nervous stroke"). Starting with a short outline of
      Mendelssohn's pathography, this paper includes and quotes for the first time all
      the contemporary accounts of his death. After considering the older medical
      interpretations, the paper considers these reports from the point of view of
      present-day neurological and psychiatric expertise. It reveals that all the
      accounts had been filed by medical laymen, so their personal impressions had
      played a major role in their reports. However, it is indisputable that it was
      pathologic brain alterations that lead to Mendelssohn's death. Weighing up and
      carefully considering the sources, the authors regard subarachnoidal hemorrhage
      (SAH) as a likely cause of death. There may even have been some kind of genetic
      predisposition, since what is reported in this paper regarding Mendelssohn's
      death also applies to the very similar symptoms and circumstances surrounding his
      sister Fanny's death.

PMID- 16586257
TI  - [Correlation of clinical aspects as well as genotype and phenotype in Wilson's
      disease on the basis of epidemiologic, clinical and cranial MRI findings].
AB  - Wilson's disease, a rare autosomal recessive disorder of hepatic copper
      transport, is characterized by a varying pattern of hepatic, neurologic and
      psychiatric symptoms. Currently, about 250 causative mutations of the ATP 7B gene
      are known. However, a correlation between genotype and phenotype according to
      these mutations is not yet clear. To elucidate a possible correlation in this
      study 39 patients with Wilson's disease were subdivided into three groups
      according to the underlying mutation in group I for homocygote respectively group
      II for compound heterocygote mutation in H1069Q and group III for other
      mutations. Clinical subtype and extent of neurologic disturbance as well as
      epidemiologic aspects, presence of psychiatric symptoms, results of acustically
      evoked potentials (Wave III, interpeak latency III-V) and findings of cranial MRI
      were considered. While psychopathological symptoms, the results of acustically
      evoked potentials and cranial MRI show a correlation to the clinical subtype of
      Wilson's disease there was no genotype-phenotype correlation on the basis of the
      mutation in H1069Q. The qualitative and quantitative pattern of results do not
      show any significant differences in the three groups of genotype. Thus, the time
      of treatment onset still has most influence on the extent of clinical
      manifestation and reversibility of the toxic copper accumulation.

PMID- 16586258
TI  - [Stress and progression in multiple sclerosis].
AB  - The hypothesis that stress might be connected to causation or exacerbation of
      multiple sclerosis has been under discussion for a long time. The current studies
      indicate that there is a coincidence between stress and disease progression.
      Besides the state of art in research different stress models will be introduced
      in the paper and the relations between disease, resources and coping will be
      discussed. Besides the influence of distressing life events on disease, the
      effect of illness-related characteristics on the coping behaviour will be
      considered in this regard. From the results of the presented studies and the
      described stress models it was concluded that the possibilities of stress
      avoiding intervention programs should be taken into account more strongly in the
      future.

PMID- 16586259
TI  - [Stability of the "amok runner syndrome"].
AB  - BACKGROUND: Running amok is considered a rare but dangerous act of violence which
      has been investigated predominantly on a case by case basis. German-wide data on
      amok cases covering the decades 1980 - 1989 and 1991 - 2000 were used to perform
      the first epidemiological study world-wide on the stability of socio-demographic,
      criminological and psychiatric variables of amok behaviour. METHODS: A content
      analysis study on nation-wide press reports of amok cases included a total of 104
      subjects who were identified by combined homicidal-suicidal acts of violence and
      fulfilled structured criteria originally defined according to former Malayan amok
      events. RESULTS: Amok cases in both decades were comparable except for the
      significant increase of weapon use, especially of firearms. Total prevalence
      showed a tendency to decline from 1 : 5.5 million to 1 : 8.5 million men per
      year, females were involved in rare single cases only. The male offenders showed
      a bimodal age distribution with a mean of 35 years. They were professionally well
      qualified, but had a 5 - 7fold higher risk of unemployment than the normal
      population. Motives and reasons for running amok were serious but not unusual,
      they varied widely and addressed all areas of daily life. Most offenders were
      characterized by abnormal personality patterns such as passive, aggressive,
      impulsive and paranoid and were in possession of firearms and previously
      convicted. Psychiatric diseases such as psychosis, paranoia, depression or
      personality disorders were present in more than 50 % of cases; further 20 % were
      intoxicated. The presence of psychiatric disorders influenced patterns of violent
      behaviour in individual subjects. Victims were predominantly unknown to the
      offenders. Close to one third of the amok runners committed suicide or were
      killed by legal authorities. CONCLUSION: Amok represents a temporarily stable
      syndrome of extreme violent behaviour even in modern industrialized societies.
      Subjects exhibit a complex combination of serious causative motives, social
      burden and psychiatric diseases which do not explain common causes of amok rather
      than the origin of amok behaviour in individual cases. Amok joins the wide
      spectrum of human homicidal-suicidal acts which show similarities in many
      aspects.

PMID- 16586260
TI  - [Drug addiction in young prison inmates with and without attention deficit
      hyperactivity disorder (ADHD)].
AB  - Prospective studies of children with ADHD have shown a high level of substance
      use disorder comorbidity, particularly when associated with social maladaptation
      and antisocial behavior. Conversely, studies of drug abusing participants and
      delinquents revealed a high prevalence of ADHD comorbidity. In this study 129
      young male prison inmates were systematically examined for ADHD and substance use
      disorders. 64,3 % showed harmful alcohol consumption. 67,4 % fulfilled DSM-IV
      criteria for any drug abuse or dependence. 28,8 % of these participants were
      diagnosed with ADHD, combined type, other 52,1 % showed ADHD residual type.
      Opioid dependence was more common in delinquents without ADHD. Addicted
      delinquents with ADHD showed worse social environment and a higher degree of
      psychopathology, including externalizing and internalizing behavior, compared to
      addicted delinquents without ADHD. Neuroticism and conscientiousness ratings of
      the addicted ADHD group, but not of those without ADHD, differed from non
      addicted delinquents. The results underline the need of adequate therapeutic
      programs for addicted young prison inmates considering ADHD comorbidity, which is
      associated with additional psychopathology and social problems.

PMID- 16586261
TI  - [Psychotropic drug-induced change of weight: a review].
AB  - OBJECTIVE: The purpose of this study is to give a systematic review of change of
      weight associated with commonly used psychotropic drugs. METHODS: Mainly based on
      a MEDLINE-supported review until April 2005, data from clinical studies with
      antidepressants, anticonvulsants, mood stabilizers and neuroleptics were scanned
      for change of weight during treatment. RESULTS: Among antidepressants
      amitryptiline and nortriptyline have the highest incidence of weight gain
      followed by imipramine. Maprotiline and mirtazapine have an intermediate weight
      increasing potential. SSRI (except paroxetine) and MAOI had no or only slight
      weight inducing effects. In contrary, bupropion was associated with weight
      reduction. Regarding mood stabilizers and anticonvulsants, a marked gain in
      weight with lithium and sodium valproate was reported frequently. With gabapentin
      and vigabatrin a slight to moderate gain in weight was found. Minor changes of
      weight were found with carbamazepine and lamotrigine. Treatment with topiramate
      and felbamate reportedly lead to weight loss. The atypical neuroleptics clozapine
      and olanzapine were frequently related to a strong gain in weight followed by
      risperidone. Quetiapine has intermediate effects. Stable weight was found with
      aripiprazole and ziprasidone. A gain in weight is less frequent with
      older/typical neuroleptics. CONCLUSION: Beside some methodological restrictions
      like inconsistent information of weight changes (e. g. percent vs. mass) and the
      small sample of available long term studies, this review specifies the incidence
      of weight changes for commonly used psychotropic drugs and might be helpful to
      look for alternatives.

PMID- 16586262
TI  - [On the history of taking up the word "irre" and its derived forms into the
      nomenclature of German psychiatry].
AB  - At the threshold from the 18th to the 19th century, the development of the
      psychiatry in Germany - as a subject of science and as a health service - made it
      necessary to find adequate terms for the new perception of mental illness and
      people suffering from it. At that time, some more or less discriminating
      expressions with origins in the medieval or early modern German, some words
      derived from the Latin language of scientists, and some new terms used in
      contemporary theories on the explanation of psychic disorder, constituted "eine
      verwirrende Vielfalt der Gattungsnamen fur psychische Krankheit" (a confusing
      multiplicity of names for mental illness) - (F. Nasse 1818). To make an end to
      this multiplicity, in the last decade of the 18th century some experts proposed
      to use terms derived from the word "irre" as standard expressions for illness,
      symptoms and patients in psychiatry as well as for the new elements of the
      emerging psychiatric health sector. The word "irre" with the meaning "geistig
      gestort" (mentally disordered) was part of the German vocabulary since the end of
      the Middle Ages. According to its advocates, it seemed to be suitable as new
      standard term, because it was not linked to discriminating prejudices with
      respect to its origin and to the understanding of that time. Therefore it met the
      contemporary demand for a more humanitarian behaviour towards ill people. But it
      took 20 years of discussion and clarification until this nomenclature was
      accepted in the new subject psychiatry and rested well established for nearly the
      next 100 years.

PMID- 16586263
TI  - [The Leipzig Magistrates Court's death sentences in the Woyzeck case].
AB  - The trial of Johann Christian Woyzeck for murder is among the most significant
      for forensic psychiatry in the 19 (th) century. The case gained worldwide fame,
      not only because of Georg Buchner's eponymous drama. A thorough analysis and
      reconstruction of the proceedings would allow more light to be shed on one of the
      major events in the evolution of modern psychiatric positions regarding criminal
      responsibility. To support this effort, this paper presents two original sources
      that have just been rediscovered in the archives, and which are of major
      importance in respect of both the Woyzeck case and the history of forensic
      psychiatry. Until now only transcripts had been available. The two documents in
      question relate to the death sentences issued by the Leipzig magistrates court
      (Schoppenstuhl). They clearly show the ruling feudal and municipal authorities'
      efforts to exploit both the general rules of procedure as well as the forensic
      testimony given by Leipzig's medical officer and professor, Johann Christian
      August Clarus, for their own restorative political interests. This is revealed by
      the fact, among others, that the legal procedures are interpreted in the
      narrowest possible way and the crux of the problem, namely the culprit's criminal
      responsibility, is not really the focus of attention. The defence does not really
      have a chance, the more so since it makes pleas that are both contradictory and
      amateurist from a psychiatric point of view. Moreover, its efforts to garner
      support from reformist forces, above all among scholars, are undermined by the
      defence team's manipulation of the facts.

PMID- 16586264
TI  - [Relevance of childhood trauma for later drug dependence].
AB  - There are various publications on the impact of the experience of violence and
      abuse during childhood as it relates to future substance abuse. This study aims
      to examine how childhood abuse differentiated by type and severity, impacts on
      future potential for substance abuse. Particular attention is paid to specific
      psychological symptoms and degree of addiction. METHODS: 100 patients being
      treated for substance abuse completed a questionnaire where they were questioned
      about a childhood history of sexual, physical and emotional abuse, neglect and
      family violence. Psychopathology and severity of addiction were assessed using
      the EuropASI and SCL-90. RESULTS: The results demonstrated that the respondents
      had been exposed to multiple risk factors in their childhood. The subjects were
      differentiated into groups according to type of abuse. The type and severity of
      psychological symptoms were measured by the SCL-90-R. The type and severity of
      psychosocial and environmental problems were measured by the EuropASI. It was
      shown that patients with a history of abuse had a significantly higher incidence
      of symptomatology, particularly of co-morbid psychological conditions. When
      differentiating victims of abuse by sex, women showed a significantly stronger
      impairment in 2 categories. These were insecurity in social contact and phobic
      fear. For all other variables of impairment, there were no differences between
      men and women. The severity of the various types of abuse was then correlated to
      the course of the disease. A strong correlation was found between severe forms of
      abuse where victims were involved in sexual abuse or family violence and future
      severe psychological symptoms.

PMID- 16586265
TI  - [Two simple questions to diagnose post-stroke depression].
AB  - BACKGROUND AND PURPOSE: Many patients develop a depression after having suffered
      a stroke. Such a Post-Stroke Depression (PSD) impairs rehabilitation and quality
      of life. PSD is underdiagnosed in spite of available treatment. Several
      questionnaires have been created to diagnose a PSD. But questionnaires have been
      considered cumbersome and time-consuming. The aim of this study was to find out
      whether two simple, standardised questions will identify those stroke patients,
      who have developed a PSD. METHODS: The two case-finding questions and the Beck
      Depression Inventory (BDI) were sent to patients of the Berlin Acute Stroke Study
      (BASS) four years after their stroke. Incomplete questionnaires were complemented
      via mail or telephone. Severity of depression was assessed by means of BDI.
      RESULTS: Out of 211 patients, 199 responded to the questionnaire (94 %). 193
      questionnaires were complete (97 %). Forty-two patients affirmed both case
      finding questions (22 %). Compared to patients, who did not affirm both
      questions, these patients had a higher BDI score (19 +/- 8 vs. 7 +/- 5; p <
      0.001). The sensitivity and specificity of the two questions were 89 % and 90 %,
      respectively. The positive and negative predictive value were 60 % and 98 %
      respectively. The number of confirmed questions (0, 1, 2) correlated well with
      the BDI score (r (2) = 0.67, p < 0.001). CONCLUSIONS: Two standardized questions
      can identify patients with PSD for further diagnostic evaluation and therapy.
      Diagnosis of PSD might be facilitated by using them as screening instrument.

PMID- 16586266
TI  - [Functional outcome after decompressive craniectomy: a retrospective and
      prospective clinical study].
AB  - Decompressive craniectomy has been revived as a radical surgical treatment in
      increased ICP. While the life saving effect is undisputable, reports about the
      functional outcome are controversial. Furthermore, there are no data comparing
      the outcome of craniectomised patients with different aetiologies. In a
      retrospective and prospective study we assessed the functional outcome of
      craniectomised patients (41 stroke and 24 traumatic brain injury (TBI) patients).
      The majority of patients considerably benefits from the rehabilitation process.
      Nevertheless, most of them remained dependent upon caregivers. In stroke patients
      there was a significant negative correlation between age and outcome. Even though
      TBI were younger than stroke patients there were no outcome differences between
      these groups. We found no correlation between the side of the hemisphere injured
      and outcome.

PMID- 16586267
TI  - [Human Metapneumovirus in hospitalized children - a review].
AB  - The human Metapneumovirus (HMPV) has been discovered by von den Hoogen et al. in
      2001 and seems to play an important role as etiologic agent in childhood
      respiratory tract infections in particular involving infants after the 6th month
      of life and toddlers. Duly considering the hitherto published studies and
      retrospective analysis of two HMPV seasons (2002-2004) at our institution this
      review focuses on children, who had to be hospitalized due to HMPV infection. The
      analysis confirmed, that among those patients there is a high proportion of
      children with pre-existing risk factors for a complicated clinical course, a high
      proportion of children with bronchiolitis or pneumonia and a relevant proportion
      of children with HMPV related apnoeas, most prevalent in the prematurely born.
      Although the first HMPV infection takes place somewhat later in infancy, the data
      do not show that HMPV infection is in general milder than RSV infection in
      hospitalized children. Clinical symptoms and radiological signs do not permit
      tentative conclusions on the causative agent. This underlines the necessity of
      specific diagnostic efforts (in case of HMPV with PCR). HMPV may cause lobar or
      segmental pneumonias difficult to distinguish from bacterial lower respiratory
      tract infection. Children admitted to the hospital with an acute exacerbation of
      asthma bronchiale or cystic fibrosis should not only be tested for RSV but also
      for HMPV. Prospective studies investigating specific therapeutic interventions or
      describing the impact and prevention of nosocomial HMPV in fection are awaited
      for. There has been one report of a meningoencephalitis possibly related to HMPV.
      Thus, liquor samples in such cases should be tested for HMPV too.

PMID- 16586268
TI  - [Therapy of monosymptomatic nocturnal enuresis in childhood and adolescence: what
      is the evidence?].
AB  - Nocturnal enuresis (bedwetting) is one of the most frequent urological symptoms
      in children, affecting about 20% of five year olds. It is a heterogeneous
      disorder with a whole variety of etiologic factors (genetic, endocrinological,
      neurobiological), particularly a dysfunction of the lower urinary tract. Despite
      the prevalence of enuresis many questions regarding the complex
      pathophysiological mechanisms remain unanswered. While nocturnal enuresis per se
      is clearly not a disease, psychosocial problems have been reported in up to 40%
      of affected children. Management strategies comprise behavioural and
      pharmacological approaches, either in isolation or combined. Although
      expectations were high, especially with pharmacological interventions, the
      results are usually disappointing with high recurrence rates. Extensive analyses
      of the available literature on the efficacy of enuresis treatment modalities
      reveal a poor quality of many trials with a whole range of methodological flaws.
      Therefore, further comparative studies of adequate methodological quality are
      needed.

PMID- 16586269
TI  - [Congenital intestinal lymphangiectasia: a rare differential diagnosis in
      hypoproteinemia in infants].
AB  - BACKGROUND: Congenital intestinal lymphangiectasia is a rare disease in
      childhood, which may already cause protein-losing enteropathy in newborns.
      PATIENT, METHODS AND RESULTS: This is a case report of an infant with generalized
      edema and protein-losing enteropathy, in whom intestinal lymphangiectasia was
      diagnosed at the age of two months. Following repetitive intravenous albumin und
      gamma globulin infusions, the elimination of long-chain fats from the diet and
      the substitution with medium-chain triglycerides (MCT) led to an improvement of
      the protein-losing enteropathy. CONCLUSION: In newborns with low level of serum
      protein and edema protein-losing enteropathy caused by congenital
      lymphangiectasia might be considered as a differential diagnosis.

PMID- 16586270
TI  - [Cow's milk allergy: guidelines for the diagnostic evaluation].
AB  - About 2% of the general population and up to 6% of children suffer from food
      allergy. Cow's milk is charged with a important role in infancy after weaning,
      since conventional formula are based on its procession. IgE-mediated and Non-IgE-
      mediated allergic reactions, which are different in manifestation and
      pathogenesis, can be distinguished. A special role play the exacerbation of
      atopic dermatitis and the gastrointestinal-food-hypersensitivity-reactions. Skin
      prick-test and determination of specific IgE are important diagnostic tools
      beside medical history. The golden standard of diagnosis is the double-blind
      placebo-controlled-food- challenge. The clear result from food-challenge allows
      to verify suspected food allergies or, on the other hand, to avoid unnecessary
      diets. Extensively-hydrolysed-formula or Amino-acidformula are a high nutritional
      value alternative in case of proved cow's milk allergy in infancy.

PMID- 16586271
TI  - Neurodevelopmental outcome at 2 years in 23 to 26 weeks old gestation infants.
AB  - BACKGROUND: Assessment of neurologic and developmental outcome at 2 years age of
      infants with gestational age (GA)<27 weeks, born between 1996-2001. PATIENTS: A
      total of 110 live-born preterm infants with GA<27 weeks. METHODS: Main outcome
      criterions: Neurologic examination (according to Touwen) and classification of
      cerebral palsy by using the Gross Motor Function Classification System (GMFCS) at
      the corrected age of 1 and 2 years; assessment of mental and psychomotor
      development by using the Griffith Mental Development scales at the corrected age
      of 2 years; growth assessment at birth, 1 and 2 years. RESULTS: Mortality was
      52%. Regular follow up was performed in 48 (91%) of the 53 surviving infants.
      Neurologic outcome: at 1 year age: 2% nonambulant cerebral palsy, 25% mild
      neurologic signs and 73% normal; at 2 years age: 4% nonambulant cerebral palsy,
      2% ambulant cerebral palsy, 4% mild neurologic signs and 90% normal neurology.
      Developmental outcome at 2 years age: 40% DQ>-1 SD, 6% DQ between -1 SD and -2 SD
      (mild delay), 35% DQ between -2 SD and -3 SD (moderate delay) and 19% DQ<-3 SD
      (severe delay). Overall disability was found in 64%, severe disability in 27% of
      the infants. Profound growth failure in weight and head circumference<3rd centile
      at 2 years age was recorded in 39 and 19% of the infants, respectively.
      CONCLUSION: Developmental delay is very common in preterm infants<27 GA and
      exceeds the number of neurological disabilities (including cerebral palsy).

PMID- 16586273
TI  - Disastrous course of recurrent infective endocarditis after tooth extraction in a
      young patient with bicuspid aortic valve.
AB  - In a patient with moderate malformations of the left-ventricular valves disregard
      of antibiotic prophylaxis after tooth extraction resulted in massive mitral- and
      aortic regurgitation. After surgical reconstruction a relapse produced an aorto
      left-ventricular fistula with septic embolizations and cardiac decompensation.
      Valve replacement with a homograft reconstituted the hemodynamic situation.
      During both episodes the Duke criteria for infective endocarditis supported the
      diagnosis.

PMID- 16586274
TI  - [3M syndrome: case history].
AB  - BACKGROUND: This case report shall draw attention to a still little known
      syndrome of primordial nanism. It is important for the differential diagnosis on
      the genetic counselling, specially with regard to the Silver-Russell syndrome.
      CASE REPORT: A striking mentally retarded (I. Q. 54) 9-year-old boy with
      primordial proportionate short stature exhibited characteristic features of the
      3M syndrome (MMM): pseudohydrocephalic dolichocephalia, short neck with
      protruding muscles, transversal furrow in the lower thorax, muscular hypotonia
      with joint laxity - "falling hands", radiographic manifestations included the
      tall vertebral bodies and gracile long bones. Furthermore there was a dent
      temporal at the left. But this feature is found on many other syndromes with
      nanosomia frontotemporal, less frequent the low position of the navel on these
      patients. The karyotype was normal, the case apparently sporadic. CONCLUSION: MMM
      can be differentiated from other types of nanosomia by clinical criterias; a
      molecular genetic proof is not yet possible.

PMID- 16586275
TI  - [Cochlear protection and surgical precision in stapedotomy with Er:YAG laser].
AB  - BACKGROUND: Using laser in stapedotomy has attracted a lot of attention since the
      nineties. It aims at minimizing complications due to hand-operated equipment,
      especially inner ear lesions, and achieving higher precision. We analyzed the
      clinical effect of Er:YAG laser with the question whether the postulated cochlea
      protection and foot plate perforation, optimized for better sound conduction, are
      achieved, compared to conventional stapedotomy. PATIENTS AND METHODS: We
      evaluated retrospectively audiometrical data including pre- and postoperative
      bone and air conduction thresholds of 114 consecutive patients, on whom we had
      performed stapedotomy and had inserted platinum-teflon prostheses. The
      intervention was done conventionally in 72 cases and in 42 cases with Er:YAG
      laser. RESULTS: In the lower and middle frequencies, laser technique resulted in
      a more pronounced improvement of bone conduction thresholds compared to
      conventional stapedotomy. The improvement of air conduction was more distinct in
      ears after laser surgery; also, the difference between air and bone conduction
      was reduced at a higher degree. CONCLUSION: Er:YAG laser in stapedotomy is
      coupled with cochlea protection, as demonstrated under clinical conditions, and
      allows higher hearing benefit of air conduction compared to conventional
      stapedotomy. Our results emphasize the impact of innovative laser technique on
      stapedotomy.

PMID- 16586276
TI  - [Three-dimensional visualization of CT of the neck for surgical planning].
AB  - BACKGROUND: Surgical planning in ENT profits from computer assisted preoperative
      visualization and planning. The informative capability is to be improved by three
      dimensional illustrating of the preoperative available data. The possibility of a
      3-D-visualization of lymph nodes stands in the center of the interest. METHODS:
      16 CT data sets with a tumor-classification of T1N1 or higher were included.
      Altogether 720 pseudo-3-D-illustrations were provided with an average of 9.3
      objects. Current algorithms were used for the segmentation and visualization and
      the results were divided in three classes. RESULTS: The average time requirement
      for visualization and segmenting amounted to 122 minutes, the minimum value is at
      61 minutes per data set. Automatic segmenting succeeded only with structures with
      clear grey tone differences to the environment. In all other cases an additional
      manual interaction had to take place. CONCLUSIONS: 3-D-Visualising of CT of the
      neck represents a new quality in preoperative planning. A clear trend at
      increasing detail loyalty and information efficiency showed up in the groups of B
      and C. It is possible to make from these pictures a quantitative statement on
      surgery relevant infiltration. Likewise conceivable are the postoperative quality
      control or planning and process control of a postoperative radio-chemotherapy.
      The automatic algorithms can be estimated as reliable. Application is still far
      from a clinically efficient use. With the rising efficiency of the computing
      systems, the improved software and the imaging systems the problems mentioned
      are, however, solvable.

PMID- 16586277
TI  - [Bilateral tumor of the nasal vestibule--a case report].
AB  - The authors report a case of a bilateral tumor of the nasal vestibule with a six
      year history of progressive impairment of nasal breathing. After microsurgical
      transnasal excision, the finding was diagnosed as bilateral nasolabial cyst.

PMID- 16586278
TI  - [Doubling of the pinna, a rare branchial arch developmental disorder].
AB  - BACKGROUND: Auricular appendices are not unusual, but doubling of the pinna is
      rare. There is still a controversy if these are derivates from the first or the
      second branchial arch. PATIENT: The case of a 3 year old girl is described with
      doubling of the pinna and hemi facial atrophia. The second pinna was on third of
      the orthotop regular auricle. It seemed to come from the tragus anlage i. e.
      originating from the first otic hillock. RESULTS: The accessory pinna was
      resected, an aesthetic result could be achieved. CONCLUSION: Morphology and
      position of accessory pinnas arise again the question of the origin of the
      auricular hillocks. This case supports the opinion of Otto that the first hillock
      only belongs to the first branchial arch and the major part of the auricle is
      originating from the hillock 2-6 i. e. to the second branchial arch.

PMID- 16586279
TI  - [Salivary duct carcinoma of the sublingual gland--a case report].
AB  - RATIONALE: Pleomorphic adenoma is the most common neoplasm of major and minor
      salivary gland origin, followed by infectious reasons and sialolithiasis. Less
      common are adenocarcinomas presented. The salivary duct carcinoma represents a
      rare variant of the group of adenocarcinomas originated from the salivary glands,
      especially extremely rare from minor salivary gland origin. CASE REPORT: We
      report about a 52 year old male patient presenting with painless, non-ulcerating
      tumor at the floor of the mouth. Since 2 weeks ingestion was painful. Further ENT
      investigations including endoscopy and scans (MRT, ultrasound) showed no
      pathology. In particular, growth of cervical lymph nodes and distant metastases
      were not revealed. A biopsy showed a rare salivary duct carcinoma of comedo-type
      originated from the left sublingual salivary gland. The patient underwent an
      operation: the tumor was extirpated in toto, and, as the pathohistological
      investigation confirmed, in sano. Additionally a neck dissection at the left side
      was performed, followed by the radiation of the tumor region and the lymphatic
      neck regions, after sufficient reconvalescence. The tumor-classification was pT3,
      pN0. Since 3 years no recurrence of the tumor was confirmed. DISCUSSION: Salivary
      duct carcinoma is a rare, high-grade malignant epithelial neoplasm, which occurs
      almost exclusively in the parotid. As presented, it can also occur in minor
      salivary glands. Histologically it is composed of structures that resemble
      expanded salivary glands. Comedonecrosis of these structures is a frequent
      feature. There is some histologic similarity to intraductal carcinoma of the
      breast. Differential diagnosis comprises adenoid cystic carcinoma, metastases of
      other adenocarcinomas, such as the carcinoma of the thyroid gland and the
      comedocarcinoma of the breast. Because of its poor prognosis a rapid and radical
      therapy is recommended. CONCLUSION: A rare case of a salivary duct carcinoma of
      sublingual salivary gland origin is presented. Usually the prognosis is poor. The
      adequate therapy is the complete surgical extirpation including the surgery of
      the regional lymphatic nodes and the additional radiotherapy.

PMID- 16586280
TI  - [Model oriented assessment of literacy performance in children with cochlear
      implants].
AB  - BACKGROUND: Although most hearing-impaired children lag behind normally hearing
      children in literacy acquisition, this aspect has hardly been addressed in the
      evaluation of language acquisition after cochlear implantation. The present study
      investigated written language abilities in 8 school-age children with cochlear
      implants. Neurolinguistic dual-route-models of written language processing
      indicate that literacy acquisition leads to the establishment of two distinct
      reading and writing strategies: a lexical one for the quick processing of known
      words and a sublexical one for decoding unfamiliar words or nonwords letter by
      letter. PATIENTS: 8 school-aged children were investigated, a very heterogeneous
      group concerning age of onset of hearing impairment, educational placement, and
      competences in sign language. However, this range is typical of the group of CI
      children. METHODS: The aim was to investigate if children with cochlear implants
      are able to establish both strategies or if they need to find a differential and
      individual access to written language. Performance within the Salzburger Lese
      Rechtschreib-Test was evaluated. Individual performance of each subject was
      analysed. RESULTS: Performance varied substantially ranging from only rudimentary
      spoken and written language abilities in two children to age-equivalent
      performance in three of them. Severe qualitative differences in written language
      processing were shown in the remaining three subjects. Suggestions for
      remediation were made and a re-test was carried out after 12 months. Their
      individual profiles of performance are described in detail. CONCLUSIONS: The
      present study stresses the importance of a thorough investigation of written
      language performance in the evaluation of language acquisition after cochlear
      implantation. The results draw a very heterogeneous picture of performance. Model
      oriented testing and analysis of performance prove to be sensible in at least a
      subpopulation of children with cochlear implants. Based on a better understanding
      of their acquired word-processing strategies, remediation programs meeting the
      needs of each individual child can be derived.

PMID- 16586282
TI  - [Subcranial resection of malignant tumors infiltrating the anterior skull base].
AB  - BACKGROUND: Survival and quality of life after subcranial resection of malignant
      tumors infiltrating the anterior skull base should be evaluated. METHODS: Data
      were acquired retrospectively from patient charts and by telephone interview.
      Quality of life was assessed with the EORTC QLQ30 and H&N35 modules. RESULTS:
      From 1996 to 2004, 19 patients (mean age 52 years, 4 woman, 15 men) were
      surgically treated via a subcranial approach. Fifteen patients suffered from
      advanced carcinoma, 3 from advanced esthesioneuroblastoma, and 1 patient had a
      fibrosarcoma. Fifteen patients received adjuvant radiotherapy. During the mean
      follow-up period of 44 months (12-109 months), 6 patients died, 1 unrelated to
      the tumor. The probability to survive 5 years was 50 %, the mean survival time
      was 72 months. Anosmia was reported by 18 of 19 patients. A tension
      pneumocephalus was observed in 2 patients, one with lethal outcome, decreased
      vision in 1 patient, loss of vision in 1, persisting diplopia in 1, deep wound
      infections in 2, and CSF leak in 2 patients. Quality of life was assessed on the
      average 36 months following end of therapy and did not differ substantially from
      other patients with head-neck malignancies. CONCLUSION: Most, malignant tumors
      infiltrating the anterior skull base can be treated curatively. The treatment
      outcome is well comparable to other head and neck tumors of corresponding stage.

PMID- 16586281
TI  - [Intraoperative bronchospasm during paranasal sinus surgery -- indicator of
      aspirin intolerance syndrome?].
AB  - BACKGROUND: The aim of this study was to evaluate whether an intraoperative
      bronchospasm is more frequent in sinus surgery than in non-sinus surgery, whether
      its appearance after application of a non-steroidal anti-inflammatory drug
      (NSAID) is an indicator of an aspirin intolerance syndrome, and whether its
      appearance can be interpreted as an aspirin provocation test. METHODS:
      Anaesthesia charts from 5 years were retrospectively analysed whether
      anaphylactic/allergic reactions or bronchospasm were observed intraoperatively.
      In these cases the ENT charts of the patients were analysed and the occurrence of
      an analgesic-induced bronchospasm was assumed according to a probability
      algorithm. PATIENTS: All operations in general anaesthesia of an
      otorhinolaryngology clinic were analysed. RESULTS: An intraoperative bronchospasm
      was observed significantly more often in patients undergoing sinus surgery than
      during other ENT operations. In 17 of 23 patients a possible/probable analgesic
      induced bronchospasm after application of NSAID was found. Diclofenac was
      intraoperatively given in 3 patients, diclofenac and metamizole in 5 patients,
      metamizole in 7 patients, paracetamol in 1 patient, and paracetamol and
      metamizole in 1 patient. CONCLUSIONS: An intraoperative bronchospasm during sinus
      surgery is not a clear indicator of an aspirin intolerance syndrome. An analgesic
      induced bronchospasm can also be observed after paracetamol and metamizole. It
      can not be interpreted analogous to an aspirin provocation test.

PMID- 16586284
TI  - [Therapy of postoperative nausea and vomiting in ENT--tardive dyskinesia as an
      adverse effect of metoclopramid--a case report].
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) are among the most common
      complications in operative medicine. Especially patients undergoing middle ear
      surgery or stapedectomy are frequently suffering from PONV. On the other hand
      vertigo might be a symptom of an operative complication. For symptomatic therapy
      a various number of different drugs is available. PATIENT: We describe the
      clinical course of a 25-years-old female patient, who presented with massive
      orofacial tardive dsykinesia after therapy with metoclopramide (MCP). She had
      stapedectomy in general anaesthesia and suffered from PONV. The dyskinesia was
      treated successfully with Biperiden 5 mg i. v. DISCUSSION: Tardive dyskinesia is
      a potential and in rare cases irreversible complication of MCP-therapy. The
      efficiacy of MCP is in controversy. Studies with 5-HT3-antagonists like
      Ondansetron or neuroleptics like Droperidol show good results in PONV especially
      after middle ear surgery. CONCLUSION: Tardive dyskinesia is a rare but possible
      drug-related adverse effect of MCP. After review of the literature we can not
      recommend MCP as an antiemetic drug in PONV.

PMID- 16586283
TI  - [Endonasal micro-endoscopic resection of sinonasal inverted papilloma].
AB  - BACKGROUND: The goal of this study was to assess the potentials and limitations
      of endonasal micro-endoscopic surgery in the treatment of sinonasal inverted
      papilloma (IP) and to demonstrate long-term results. PATIENTS AND METHODS: From
      1989 to 2005, 64 patients underwent resection of IP via an endonasal approach
      using either the endoscope or microscope. Charts were reviewed retrospectively
      for presenting symptoms, radiological and intraoperative data. All patients were
      followed by endoscopic and MRI control during a period of up to 174 months,
      median follow-up was 78 months. RESULTS: Our study group consisted of 26 male and
      38 female patients with an average age of 54.3 years. The majority of the
      patients (67 %) complained of unilateral nasal obstruction. 52 patients (81 %)
      were referred for primary surgery. In 12 cases (19 %) recurrent tumors were
      operated. According to the Krouse classification for IP the tumors were staged as
      T1 = 11 (17 %) cases, T2 = 37 (58 %) and T3 = 14 (22 %). In two patients a
      squamous cell carcinoma was associated with an IP ( = T4 stage). Most tumors were
      localized within the nasal cavity (72 %) or the anterior ethmoid (62 %). In 10
      patients an infiltration of the bony skull base was present. During the follow-up
      period 6 patients developed recurrencies corresponding to an overall recurrence
      rate of 9.4 %. CONCLUSIONS: The advances in endonasal micro-endoscopic surgery
      allow both safe and effective removal of IP with low morbidity, and therefore it
      should be the approach of the first choice. The osteoplastic approach combined
      with endonasal surgery is suitable in far lateral located IP. Close follow-up is
      mandatory to ensure the surgical success.

PMID- 16586285
TI  - [Experiences with the subfrontal approach to manage extensive fractures of the
      frontal skull base].
AB  - BACKGROUND: Surgical management of multiple traumatized patients with head and
      neck trauma is highly individualized and depends on a number of factors including
      etiology, intracranial pressure, concomitant injuries, patient age and the
      possibility of an interdisciplinary procedure. Severe head and neck trauma are
      often connected with fractures of the frontal skull base or nasoethmoido-orbital
      complex and CSF leakage. If there is suspicion of a CSF leakage surgical
      management to cover the dura-defect is essential. An intradural approach is
      necessary in case of concomitant intradural injuries while primary extradural
      access provides excellent exposure of the rhinobasis with low morbidity and good
      results. METHODS AND MATERIAL: We report about our surgical experiences of 55
      patients with severe frontobasal trauma, who were operated between 1/1999 and
      11/2003. The subfrontal approach according to Raveh we had chosen in 20 patients
      which were operated by an interdisciplinary team together with the neurosurgeons.
      With an average follow up of 36 month we report about early and late
      complications. RESULTS: 19/20 patients showed sufficient coverage of the CSF
      leakage, once a revision surgery was necessary. Finally this patient had also an
      unobjectionable coverage of the CSF leakage. We saw no major complication like
      meningitis or brain abscess, intracerebral haematoma or surgical injury of the
      orbital wall. The most important complication was an anosmia, which depending on
      the extension of the approach results in any patients. CONCLUSIONS: Our results
      show that the subfrontal approach is a reliable method to explore extensive
      frontal dural defects and to reconstruct fractures of the frontal skull base
      without additional trauma to the frontal lobe.

PMID- 16586286
TI  - [Subjective and objectifying olfactometry by means of flow-olfactometer].
AB  - BACKGROUND: Is the flow-olfactometer OM2S suitable for subjective and
      objectifying screening of olfactory function, additional to its use for
      chemosensory evoked potentials? METHODS: 53 normosmics were challenged prenasally
      and synchronously with inspiration by two short weak, moderate and strong
      hydrogen sulfide (H (2)S)- and phenylethyl alcohol (PEA)-stimuli. The subject
      pressed a button if there was an olfactory perception. The respiratory nasal
      pressure changes were recorded continuously via a differential pressure
      transducer. The alterations of breathing pattern during olfactory stimulation
      were calculated using a custom made LabView software. The interstimulus interval
      was at least 3 minutes, the respiration had to be regular. RESULTS: The detection
      rate (79 - 98 %) was dependent on quality of odor and its concentration during
      stimulation. H (2)S-stimuli were detected more frequently than PEA-stimuli. The
      frequency of detection with simultaneous alteration of breathing pattern was
      independent of quality of odor and strength of odor concentration. 64 % of the
      subjects detected both weak H (2)S as well as changed synchronously their first
      poststimulatory breath. CONCLUSION: The H (2)S-detection threshold was estimated
      both by subjective data and by data of olfactory evoked respiration changes. The
      flow-olfactometer by Kobal is very well suitable for subjective and respiration
      olfactometry, too.

PMID- 16586287
TI  - [The custom-fit voice prosthesis, for treatment of periprothetic leakage after
      tracheoesophageal voice restoration].
AB  - BACKGROUND: Leakage around an indwelling voice prosthesis is detected during 13%
      up to 27% of all replacement procedures of voice prosthesis and causes serious
      complications in further voice restoration of the laryngectomee. Lots of
      therapeutic options to stop periprothetic leakage have been described (Injection
      of Bioplastique, autologous fat or collagen, suture techniques, spacer therapy)
      without convincing success rates. METHODS: Custom-fit voice prostheses are
      ordinary indwelling voice prostheses (Blom-Singer low pressure Indwelling 20 fr)
      with enlarged flanges and reduced shaft length that are individually sized for
      the shunt of the laryngectomee. Especially enlarging the esophageal flange
      provides a tight sealing of leakage around the prosthesis. PATIENTS: In a one
      year lasting clinical trial 692 voice prostheses were changed. In 77 cases
      periprothetic leakage was detected and fistulas were fitted with individually
      sized voice prostheses. RESULTS: In 76 cases total control of leakage was
      achieved without any specific complications taking place. Moreover two types of
      leaking tracheoesophageal fistulas were distinguished, a dilated-atrophic and an
      infected-necrotic type. 57% of the fistulas were dilated-atrophic type and 43% of
      the fistulas were classified infected-necrotic type. Infected-necrotic fistulas
      needed enlarged flanges tracheal an esophageal for tight sealing in 91% of the
      cases whereas dilated-atrophic fistulas needed double flanges only in 45%. 70% of
      infected-necrotic type fistulas needed only one singular history of a custom-fit
      prosthesis and could be changed back to ordinary indwelling prostheses after
      healing had taken place. CONCLUSIONS: As the insertion of a modified prosthesis
      is only slightly more effort than an ordinary voice prosthesis insertion, the
      success rate is high und complications are rare we recommend the custom-fit voice
      prosthesis for treatment of periprothetic leakage.

PMID- 16586288
TI  - [Improved accuracy and precision of the automated shaver (navigated control) in
      functional endoscopic sinus surgery].
AB  - BACKGROUND: The feasibility of a navigate-controlled Shaver for the paranasal
      sinus surgery was proven in an initial study. Deficits showed up in the
      conversion of the planed cavity. Goal of this study is (1) the development and
      evaluation of a FESS demonstrator for the investigations to the surgical accuracy
      and (2) the evaluation of the resulting surgical accuracy for registration and
      conversion of the work space with an improved rigidity of the Shaver and a
      completely revised study design. METHODS: As a demonstrator for the navigate
      controlled resection of a volume through the Shaver a two-piece plastic head with
      an anatomical head and soft tissue model was designed. The investigation of the
      surgical accuracy takes place with 417 measurements to 4 different fiducial
      markers on the demonstrator head. The measurements for the deviation of the
      resulting cavity from the planned volume was realised with a work space by 24 x
      24 x 30 mm. The 5 walls of the cavity were seized with 80 measuring points for
      each level and thus altogether 2000 measured values (5 models x 5 levels x 200
      points). RESULTS: The described demonstrator showed itself suitable for the close
      to-application attempts to the surgical accuracy. The maximum deviation A (max)
      indicated position of the Shaver from the reference value amounted to 1,93 mm.
      The maximum average value of the exceeding of a planned cavity amounts to 1,62
      mm. CONCLUSIONS: Based on these results a virtual safety passage of 2.00 mm is
      sufficient. The study refers the clinical serviceability of the navigate
      controlled Shaver in paranasal sinus surgery.

PMID- 16586289
TI  - [Adenoid cystic carcinoma secondary to heterotopic salivary gland tissue of the
      cervical lymph nodes].
AB  - BACKGROUND: The presence of heterotopic salivary gland tissue in intra-,
      periparotideal and cervical lymph nodes is not an uncommen finding. In some rare
      cases the salivary gland inclusions in lymph nodes may undergo neoplastic
      transformation. PATIENT AND METHODS: An isolated and indolent tumor was detected
      in level III in the right cervical area in a 60 year-old male patient. The
      histological assessment of the extirpated node seemed to indicate lymph node
      metastasis of an adenoid cystic carcinoma. The radiological and endoscopic
      findings did not reveal a primary tumor. RESULTS: Due to the fact of missing of a
      primary tumor, the diagnosis of an adenoid cystic carcinoma in heterotopic
      salivary gland tissue of the cervical lymph node was established after long-term
      observation. CONCLUSION: After exclusion of an occult carcinoma of the salivary
      glands, the possibility of malignant transformation of heterotopic intranodal
      salivary gland inclusions should be considered in patients suffering from
      salivary gland carcinoma in the area of the cervical lymph nodes.

PMID- 16586290
TI  - [Extraosseous osteosarcoma of the thyroid gland].
AB  - Extraosseous osteosarcomas are very rare malignant neoplasms that have been
      published in 300 cases so far. Manifestation within the thyroid gland was
      described in 6 cases only. We report a 69 year old female who suffered from
      enlarged recurrent struma after primary resection and radiotherapy 5 years ago.
      Histology revealed a high grade extraosseous osteosarcoma. Presenting the
      patient's clinical, radiological and histological findings the therapeutical
      options of this rare tumor entity are discussed.

PMID- 16586291
TI  - [Extramedullary manifestation of plasmocytoma in ENT].
AB  - Plasmocytomas are non-Hodgkin's tumors which occur with an incidence of
      4/100,000. Malignant plasma cells in bone marrow produce monoclonal antibodies
      which are typically found in urine and blood samples. In rare instances
      plasmocytoma occur exclusively in extramedullary locations preferring head and
      neck region. We report about two patients with extramedullary plasmocytoma, one
      of them with an extremely rare triple manifestation in the upper airway.

PMID- 16586292
TI  - [Simultaneous papillary carcinoma in a thyroglossal duct remnant and the thyroid
      gland].
AB  - BACKGROUND: In 1 % of the thyroglossal duct cysts malignant transformation is
      found with predomination of the papillary carcinoma (80 %). CASE REPORT: We
      present the case of a 51 year old man with a synchronic papillary carcinoma in a
      thyroglossal duct remnant and a microcarcinoma of the thyroid gland. After
      exstirpation of a thyroglossal duct cyst histological examination identified a
      papillary carcinoma. Postoperative staging uncovered enlarged lymph nodes but no
      abnormalities in the thyroid gland. Cervical lymphadenectomy and total
      thyroidectomie was performed. On histological examination a synchronic
      microcarcinoma of the thyroid was shown. CONCLUSION: Only 7 similar cases have
      been published in literature before. Because of the rare incidence no therapeutic
      standard could be established so far. We discuss our therapeutic approach as well
      as the relevant literature.

PMID- 16586293
TI  - [Diagnostic and therapeutic management of a big cyst at the floor of the mouth--a
      case report].
AB  - BACKGROUND: The growth of dysontogenetic cysts at the floor of the mouth is
      considered as a rare condition. Cysts of the floor of the mouth may be
      differentiated depending on location or on histopathologic-embryological criteria
      into dermoids, epidermoids and teratomas. PATIENTS AND METHODS: We report a case
      of a large cyst at the floor of the mouth and present the results of clinical
      examination, preoperative diagnostics and surgical approach. RESULTS: The tumour
      was resected by an enoral operation. Histological findings confirmed a large
      sublingual epidermoid cyst. There were no complication or relaps during
      postoperative course. The case is discussed within the framework of scientific
      literature. CONCLUSIONS: Dysontogenetic cysts should be considered in
      differential diagnosis of tumours of the floor of the mouth. Diagnostic and
      surgical management depends first of all on size and location of dysontogenetic
      cysts.

PMID- 16586304
TI  - [Insights and questions of a reconstructive and process analytical counselling
      research].
AB  - The author discusses some phenomena which can become the object of investigation
      in a counselling research which is reconstructive and tries to discover social
      processes. These phenomena become visible in some excerpts from qualitative data:
      a narrative interview with a social worker on his work with a client, an
      autobiographical narrative interview with a client of a counselling centre, and
      transcriptions of an initial contact with clients and the subsequent professional
      case discussion. He attempts to show which insights can be achieved in applying
      procedures of narrative and interaction analyses and in triangulating different
      types of data - insights which are relevant for research on counselling. When
      (future and currently practicing) professionals become familiar with such
      procedures they can acquire a self-critical and self-reflexive stance on their
      own practice.

PMID- 16586305
TI  - [Group therapy following lung transplantation -- first experiences with a theme
      centered "life management group"].
AB  - Lung transplantation is a drastic life event that usually takes place in the
      preterminal phase of a lung disease. Although a lung transplantation increases
      the quality of life considerably, patients still face a range of physical and
      psychosocial strains. This article presents experiences made with a "Life
      Management Group" for lung transplantation patients. The aim of the eight group
      meetings was to encourage the sharing of experiences between patients and to
      support them in their active and competent realizations of desires and plans.
      Physical health, self-identity of lung transplant recipients, growing problems
      financing medical treatment and the forming of doctor-patient-relationships were
      the important issues. Patients were able to reach a higher level of self
      efficiency; they could use active coping strategies and develop their social
      networks. Positive experiences were made with the implementation of group therapy
      for lung transplantation patients. Lung transplant recipients have to deal with
      specific problems of identity. On the other hand, there are growing health
      economic questions also from the patient's point of view.

PMID- 16586306
TI  - [Surrogate end point fallacies -- the urge for randomized trials with clinical
      endpoints].
AB  - Evidence increases that reliance on surrogate endpoints may be detrimental. This
      is particularly relevant for preventive medicine. Most impressive examples are
      hormone replacement therapy, vitamin therapy, and drug treatment of
      cardiovascular risk factors. Only a few of the oral antidiabetic agents have been
      studied in randomised trials using clinically relevant outcome measures. Most of
      these drugs or drug combinations turned out to be more dangerous than beneficial.
      They increased morbidity and mortality despite their blood glucose lowering
      effects (surrogate endpoints). New compounds are used without evidence of
      clinical benefit in millions of people worldwide. There is also an increasing
      number of examples on surrogate end point fallacies related to non-drug
      interventions (psychological, nursing, educational, social policy).

PMID- 16586307
TI  - ["Knowing--enjoying--better living". A seminar for persons with psychosis to
      improve their quality of life and reduce their vulnerability].
AB  - As a result of a recent paradigm change in medicine the improvement of quality of
      life has become a central goal of treatment next to reducing symptoms. In order
      to address this demand we designed a new psychoeducational program for
      outpatients, which -- in contrast to traditional psychoeducation -- attaches as
      much importance to quality of life topics as it does to illness related topics.
      The seminar was developed especially in view of the score resources available
      today. First results of the evaluation are presented. METHOD: Psychiatrists in
      the community are encouraged to refer patients suffering from schizophrenia or
      schizoaffective disorders to this psychoeducational program as an additional
      component to regular treatment. The program is carried out in 9 group sessions at
      weekly intervals with 6-8 group members. At the beginning and at the end of the
      seminar different objective and subjective outcomes were assessed and predictors
      for seminar success were identified. RESULTS: 98 participants could be included
      in data analysis. After completing the program the seminar participants had
      significantly more knowledge about the illness, a significantly better quality of
      life and significantly more competence and control. Furthermore there were
      changes in the illness concept: prejudices about medication decreased, confidence
      in medication increased, and beliefs about susceptibility to illness and to
      relapse increased. CONCLUSIONS: First experiences with a psychoeducational
      seminar for persons with psychosis, putting equal stress on disease related and
      quality of life topics are encouraging, but require further confirmation through
      a randomised controlled trial.

PMID- 16586308
TI  - [Patients' assessments of acute psychiatric day hospital and inpatient care.
      Analyses of open questions within the context of a randomised controlled trial].
AB  - OBJECTIVE: Within the context of the EDEN-study, a multi-centre randomised
      controlled trial comparing acute psychiatric day hospital with inpatient care,
      patients' assessments of treatment as well as their setting-preferences for
      future treatment have been studied. METHOD: Patients' assessments were collected
      using the Clients' Scale for Assessment of Treatment (CAT). The quantitative
      content analysis refers to the answers to the open questions of the CAT by all
      day hospital patients and inpatients in the Dresden project centre who completed
      the questionnaire one week after admission and again at discharge. RESULTS: Day
      hospital patients as well as inpatients assessed their treatment altogether as
      pleasant and effective. Interpersonal contact to the staff and other patients was
      evaluated as sound and helpful. Differences between the settings appeared
      primarily with regard to criticisms: Day hospital patients were mainly
      dissatisfied with their daily routine, inpatients criticized particularly
      structural conditions such as premises and food. In case of a hospital
      readmission, the majority of the patients would prefer that setting they had been
      randomised to within the EDEN-study. However, a tendency to prefer treatment in
      the day hospital was found. CONCLUSIONS: Acute mentally ill patients provide a
      substantially favourable assessment of both day hospital and inpatient care.
      Particularly the criticism of the day hospital patients contains important
      information for improving the quality of psychiatric care.

PMID- 16586309
TI  - [Cardiac MR tagging: optimization of sequence parameters and comparison at 1.5 T
      and 3.0 T in a volunteer study].
AB  - PURPOSE: The aim of this study was the optimization of a gradient echo (GRE) MR
      tagging sequence at 3.0 T in comparison to 1.5 T in order to obtain the best
      image contrast between the myocardium, tag lines and blood signal. Theoretically
      expected improvements of signal-to-noise (SNR) and contrast-to-noise ratios (CNR)
      were also calculated. MATERIALS AND METHODS: 14 healthy volunteers (8 male, 6
      female; mean age 43.4 +/- 10.3 years) were scanned using a 3.0 T as well as a 1.5
      T whole-body system. A GRE flash-2 D tagging sequence was evaluated
      (midventricular short axis view) by varying the flip angle (8 - 16 degrees ),
      slice thickness (4 - 8 mm; fixed flip angle 1.5/3.0 T: 12 degrees /8 degrees ,
      tag size 8 mm) and tag size (4 - 8 mm, fixed flip angle 1.5/3.0 T: 12 degrees /8
      degrees , slice thickness 6 mm). The field of view, acquisition time and temporal
      resolution (45 ms) were kept constant. Qualitative and quantitative image
      analysis was performed by calculating the SNR, CNR (tag) as well as the relative
      contrast between the myocardium and tag lines (RCMT). RESULTS: Based on
      individual comparison, the best imaging protocol was found at a slice thickness
      of 6 mm, tag size of 8 mm, optimized flip angle of 8 degrees (3.0 T) and 12
      degrees (1.5 T), respectively. Compared to 1.5 T, a significantly higher overall
      image score was determined (mean +/- sd; 3.2 +/- 0.2 vs. 2.7 +/- 0.4) and a
      strong correlation between the CNR (tag) and RCMT for flip angle alpha and the
      slice thickness was found. A higher field strength resulted in an 80 % increase
      in the CNR (tag) compared to 1.5 T (mean 10.7/6.1). Furthermore, the SNR was
      improved by 35 % (mean 20.6/15.3) and the RCMT by 35 % (mean 0.47/0.35).
      CONCLUSION: Myocardial tagging at 3.0 T has shown superior image quality in
      comparison to 1.5 T due to a higher baseline SNR and an improved CNR as well as
      RCMT. The suppressed fading of the tags enables the accessibility to the
      diastolic phase of the cardiac cycle.

PMID- 16586310
TI  - [Eosinophilic granuloma of the spine].

PMID- 16586312
TI  - [Retroperitoneal solitary fibrotic tumor with primary liver metastases].

PMID- 16586311
TI  - [Hypodense kidney lesion and nonspecific clinical symptoms--differential infarct,
      abscess, lymphoma diagnosis].

PMID- 16586313
TI  - [Malignant cyst transformation of the Mullerian ducts: a rare tumor in the
      child].

PMID- 16586314
TI  - [MR coronary angiography with MS-325, a blood pool contrast agent: comparison of
      an inversion recovery steady-state free precession with an inversion recovery
      fast low angle shot sequence in volunteers].
AB  - PURPOSE: To compare the signal-to-noise and contrast-to-noise ratio as well as
      the image quality of 3D inversion recovery steady-state free precession (IR-SSFP)
      and 3D inversion recovery fast low angle shot (IR-FLASH) sequences for contrast
      enhanced breath-hold MRCA. MATERIALS AND METHODS: 24 healthy volunteers (10
      female, 14 male, mean age 29.8 +/- 6.1 years) were involved in this study. All
      examinations were performed on a 1.5 T MR scanner (Magnetom Sonata, Siemens,
      Germany) after injection of 0.05 mmol/kg body weight MS-325 (EPIX
      Pharmaceuticals, Cambridge, MA and Schering AG, Berlin, Germany). MRCA was
      performed using IR-SSFP (TR 3.8 ms, TE 1.6 ms, FA 65 degrees , 35 phase encoded
      steps, bandwidth 540 Hz/pixel, slice thickness 1.5 mm, in-plane resolution 1.2 x
      0.9 - 1.4 x 1.0 mm) and IR-FLASH (TR 3.8 ms, TE 1.6 ms, FA 25 degrees , bandwidth
      490 Hz/pixel, slice thickness 1.5 mm, in-plane resolution 1.2 x 0.9 - 1.4 x 1.0
      mm) sequences. For all scans the inversion time was set to null the signal
      intensity of the myocardium. Signal-to-noise ratio (SNR) as well as contrast-to
      noise ratio (CNR) measurements (blood versus myocardium) were performed. The
      image quality was assessed based on a 5-point scale ranging from 1 (excellent) to
      5 (non-diagnostic) by two radiologists in consensus. RESULTS: The mean signal-to
      noise ratio of blood (27.7 +/- 4.7 vs. 22.6 +/- 4.9, P < 0.0001) and the contrast
      to-noise ratio (21.0 +/- 4.3 vs. 15.8 +/- 4.3, P < 0.0001) showed significantly
      higher values for IR-SSFP sequences. The mean image quality scores were
      significantly higher for SSFP (3.6 +/- 0.7) than FLASH (2.8 +/- 0.9) sequences (P
      < 0.05). CONCLUSION: IR-SSFP sequences show a considerable overall improvement in
      image quality compared to IR-FLASH sequences for MRCA after injection of a
      gadolinium-based blood pool contrast agent.

PMID- 16586316
TI  - [Preoperative diagnosis of concealed duodenal diverticulum].

PMID- 16586315
TI  - [Whole-body MR angiography: comparison of two protocols for contrast media
      injection].
AB  - PURPOSE: To compare two injection strategies for contrast media injection in
      whole-body MR angiography quantitatively and qualitatively with regard to
      contrast and image quality. MATERIAL AND METHODS: 40 patients were examined at
      1.5 Tesla using either a single injection protocol or a double injection protocol
      with two separate bolus injections. Vessel regions I (supraaortic/thoracic), II
      (abdominal/pelvic), III (upper legs) and IV (lower legs) were examined in the
      following order: single injection: I, II, III, IV, double injection: I and IV
      after the first injection, II and III after the second bolus injection.
      Quantitative evaluation: SI measurements were carried out in 2 arteries per
      region. Contrast values were calculated. Qualitative evaluation: Evaluation of
      regions I-IV regarding vessel contrast, venous overlay and image quality on a
      five-point scale by two reviewers in consensus. The Mann-Whitney-U test was used
      to test the differences for significance. RESULTS: Quantitative evaluation: Using
      the double injection protocol, significantly higher contrast values in regions I
      and II and significantly lower contrast values in the subregions IIIa (upper part
      of III) and IVb (lower part of IV) were obtained (p < 0.05). The mean contrast
      values in subregions IIIb (lower part of III) and IVa (upper part of IV) were
      lower using the double injection protocol, but not significantly. Qualitative
      evaluation: Using the double injection protocol, region II was rated
      significantly higher (mean ratings: 3.55, 3.45 and 3.5 versus 2.7, 2.5 and 2.55;
      p < 0.05) and region III significantly lower (mean ratings: 3.1, 2, 2.5 versus
      3.9, 3.1 and 3.55; p < 0.05) for all three examined criteria. When using the
      double injection protocol, ratings were significantly lower in region IV
      regarding vessel contrast and image quality (mean ratings: 2.4 and 2.15 versus
      3.45 and 3.15; p < 0.05). The ratings regarding venous overlay in region IV
      showed no significant differences (mean ratings: 2.15 versus 2.75; p > 0.05).
      CONCLUSION: Due to the better results in the supraaortic/thoracic and
      abdominal/pelvic regions, the double injection protocol is preferred. However,
      both protocols require further improvement.

PMID- 16586317
TI  - [Tuberculous sepsis -- nothing really new and still a challenge!].

PMID- 16586318
TI  - [Tuberculous osteomyelitis of the skull cap with epidural and subgaleal
      tuberculoma].

PMID- 16586320
TI  - Bone augmentation: past, present, and future.
AB  - Painful skeletal and vertebral conditions caused by degeneration, fractures,
      infection, and neoplasm are common and associated with high morbidity and
      mortality. Since the introduction of modern orthopedic surgery these conditions
      have been treated with a multitude of techniques. Bone augmentation and grafting
      have emerged as integral parts of orthopedic reconstructive, reparative, and
      palliative surgery. As imaging-guided therapy has developed, image-guided
      procedures to achieve bone augmentation have also emerged. It is important for
      the radiologist to understand the materials and methods used to achieve bone
      augmentation. A variety of materials are available for the application of hone
      augmentation. Methods used to accomplish bone augmentation often are performed
      under image guidance. Applications in the axial skeleton include vertebroplasty,
      kyphoplasty (balloon-assisted vertebroplasty), sacroplasty, and acetabuloplasty.
      This article discusses the development, current trends, and possible future
      directions of bone augmentation.

PMID- 16586321
TI  - Intradiscal therapies for discogenic pain.
AB  - Since the first injection of chymopapain in 1963, percutaneous intradiscal
      therapies have been used to treat discogenic back and leg pain. The percutaneous
      discectomy techniques treat contained disc herniations not by resecting the
      prolapsed disc material but rather through central decompression of the disc. By
      removing a small volume of tissue from the disc nucleus, a large reduction in
      overall disc pressure is achieved with consequent relief of neural compression.
      DISC Nucleoplasty and Dekompressor are the two leading percutaneous discectomy
      technologies currently. Although rigorous clinical testing of their efficacy is
      ongoing, there has now been a 40-year history confirming the concept of
      percutaneous disc decompression, and initial results are very promising.
      Discogenic low back pain can also arise from annular tears and other forms of
      internal disc derangement (IDD). Annuloplasty techniques, such as IntraDiscal
      Electrothermal Therapy (IDET) and discTRODE, have been developed over the past
      decade that thermally treat the lesions of IDD. Although the therapeutic
      mechanisms of thermal annuloplasty have yet to be fully elucidated, research
      studies demonstrate that the procedure can be effective for appropriately
      selected patients with degenerative disc disease characterized by
      discographically proven painful annular fissures. Other novel intradiscal
      therapies are emerging for percutaneous treatment of discogenic pain and await
      more widespread clinical evaluation.

PMID- 16586322
TI  - Magnetic resonance--guided musculoskeletal interventional radiology.
AB  - As an imaging modality, magnetic resonance (MR) guidance has great potential to
      direct diagnostic and therapeutic procedures performed in the musculoskeletal
      region and influence patient management. MR-guided interventional procedures
      involving bone, soft tissue, intervertebral discs, and joints are safe and
      sufficiently effective for use in clinical practice. This article discusses and
      illustrates the procedural characteristics and techniques when performing MR
      guided musculoskeletal interventions. Biopsy procedures are similar to other
      modalities for bone and soft tissue lesions. MR guidance is advantageous if the
      lesion is not visible by other modalities and for regions adjacent to hardware
      and implants, subselective targeting, intra-articular locations, and
      periarticular cyst aspiration. MR guidance has also been used for a host of spine
      injections and pain management procedures such as sacroiliac joint injections,
      discography, transforaminal epidural injection, selective nerve block,
      sympathetic block, celiac plexus block, and facet joint cryotherapy neurotomies.
      Future directions of clinical applications include tumor ablation and
      multimodality procedure suites. MR-guided musculoskeletal procedures will
      continue to be a growth area particularly for the diagnosis and treatment of bone
      and soft tissue neoplasia.

PMID- 16586323
TI  - Maximal accumulated oxygen deficit and blood responses of ammonia, lactate and pH
      after anaerobic test: a comparison between international and national elite
      karate athletes.
AB  - The purpose of this study was to compare maximal accumulated oxygen deficit
      (MAOD) and the time course of blood markers of the anaerobic metabolism in
      response to exhaustive supramaximal test in two elite (international vs.
      national) class karate athletes. Ten male international competitors from the
      French national team (Int, age 21.2 +/- 3.1 years, 71.9 +/- 11.4 kg) and eight
      national class (Nat, 23.7 +/- 2.4 years, 70.7 +/- 12.2 kg) athletes with a
      similar maximal oxygen uptake of 57.6 and 59.4 ml . kg (-1) . min (-1),
      respectively, were involved in this study. The MAOD was determined after an
      exhaustive supramaximal exercise (2 - 3 min at 140 % of their VO2max velocity) on
      a treadmill ergometer. Blood lactate, pH and plasma ammonia were determined at
      rest, immediately at the end of exercise and during the recovery period at 2, 4,
      6, 8, 10 and 15 min. After the supramaximal exercise, a dramatic higher increase
      in the blood concentration of ammonia until its peak was observed in the Nat
      compared with the Int. Time course of [NH4+] and [La] reveals significant (p <
      0.01) differences between the two groups. Peak values for [H+] (89.2 +/- 6.7 vs.
      75.9 +/- 8.8 nmol . l (-1); p < 0.01), [NH4+] (180 +/- 67.9 vs. 118.7 +/- 22.7
      micromol . l (-1); p < 0.05) and [La] (20.7 +/- 2.7 vs. 17.9 +/- 1.1 mmol.l (-1);
      p < 0.05) were higher in Nat compared with Int group, respectively. However, the
      MAOD was similar in both groups (67.8 +/- 8 ml . kg (-1) and 64.5 +/- 6.4 for Int
      and Nat groups, respectively). These data suggest that ammonia and lactate
      accumulation are sensitive to the level of performance in karate. Higher
      concentrations of these metabolites in blood after supramaximal exhaustive
      exercise may be related to either higher anaerobic contribution to energy supply
      in Nat or higher removal ability in the Int group.

PMID- 16586324
TI  - Concentric and eccentric muscle fatigue of the shoulder rotators.
AB  - Previous research has demonstrated fatigue resistance for eccentric compared with
      concentric muscle contractions in the lower extremity. The purpose of this study
      was to determine if eccentric fatigue resistance was also evident in the internal
      and external rotators of the shoulder. Ten subjects performed three sets of 32
      maximum isokinetic contractions in shoulder internal and external rotation at 120
      degrees /s. One arm performed eccentric contractions and the contralateral arm
      performed concentric contractions. Subjects were also tested for isometric
      strength prior to and immediately following the isokinetic contractions. Percent
      change in isokinetic torque (first five repetitions versus last five for each
      set) and isometric torque was compared between the arms performing eccentric and
      concentric contractions. Fatigue with isokinetic contractions was not different
      between eccentric and concentric internal rotation (25 % vs. 26 %, p = 0.76) and
      external rotation (24 % vs. 32 %, p = 0.11). Similarly, fatigue with isometric
      contractions was not different between eccentric and concentric internal rotation
      (11 % vs. 5 %. p = 0.33) and external rotation (15 % vs. 7 %, p = 0.07). These
      results indicate that unlike previously described fatigue resistance for
      eccentric muscle contractions in the quadriceps, dorsiflexors and plantarflexors,
      fatigue was not different between eccentric and concentric muscle contractions of
      the internal and external rotators of the shoulder.

PMID- 16586325
TI  - Characteristics of inline speedskating--incremental tests and effect of drafting.
AB  - Competitive inline speedskating combines a movement pattern similar to
      speedskating on ice with pack-oriented competition modes known from cycling. The
      deep-seated body position leads to high static load and, thus, restricted blood
      flow within propulsive muscles. This condition may affect lactate kinetics and
      limit V.O (2peak). The present study compares physiologic reactions to graded
      cycling and skating exercise among top-level inline speedskaters and quantifies
      the effect of drafting. Eight male inline speedskaters of the top national level
      were examined. The study consisted of two graded exhaustive exercise tests
      (cycling and speedskating) and a pairwise drafting test. All tests were carried
      out with simultaneous gas exchange (MetaMax 2, Cortex, Germany) and heart rate
      measurements as well as determination of blood lactate concentrations. Maximal
      values of oxygen consumption (cycling: 4.91 +/- 0.60; skating: 4.85 +/- 0.50 l .
      min (-1); p = 0.78), lactate concentration, or heart rate were similar for
      cycling and skating. At workloads corresponding to blood lactate concentrations
      of 4 mmol . l (-1) oxygen uptake (cycling: 3.24 +/- 0.65; skating: 3.97 +/- 0.40
      l . min (-1); p < 0.05) and heart rate (cycling: 162 +/- 9; skating: 173 +/- 6
      min (-1); p < 0.05) were significantly higher during skating. The differences in
      heart rate ranged between - 2 and 23 min (-1). The drafting effect was 15 +/- 6 %
      at 30 km . h (-1) (3.34 +/- 0.19 vs. 2.83 +/- 0.29 l . min (-1)) and 14 +/- 5 %
      at 33 km . h (-1) (3.87 +/- 0.26 vs. 3.32 +/- 0.27 l . min (-1)). During inline
      speedskating the attainment of VO2peak is not impaired when compared to cycling
      exercise. However, the derivation of exercise prescriptions from a stepwise
      cycling test does not seem appropriate. The drafting effect of inline
      speedskating is within the range known from cycling.

PMID- 16586326
TI  - Effects of the time of day on repeated all-out cycle performance and short-term
      recovery patterns.
AB  - The effect of the time of day on repeated cycle sprint performance and short-term
      recovery patterns was investigated in 12 active male subjects (23+/-2 years,
      76.4+/-4.2 kg, 1.80+/-0.06 m, 9.5+/-4.5 h . week (-1) of physical activity).
      Subjects performed ten 6-s maximal sprints inter-spaced by 30 s rest in the
      morning (08 : 00-10 : 00 h) and in the evening (17 : 00-19 : 00 h) on separate
      days. During the intermittent exercise, peak power output (P (PO), watts), total
      mechanical work (W, kJ), peak pedalling rate (P (PR), rev . min (-1)), and peak
      efficient torque (P (TCK), Nm) were recorded. The values at the 1st, the 5th, and
      the 10th sprints were used as mechanical indices of fatigue occurrence. Intra
      aural temperature and maximal voluntary contraction of knee extensors muscles
      (MVC) were measured before (pre), immediately after (post) the cycle bouts and
      following a 5-min passive recovery period (post 5). The MVC indices were used to
      further confirm occurrence of neuromuscular fatigue and to assess short-term
      recovery patterns from all-out intermittent effort. During the MVC,
      electromyographic activity of the vastus lateralis muscle was recorded and
      analysed as its root mean square (RMS). The torque produced per unit RMS was
      calculated and used as index of neuromuscular efficiency (NME). A main effect for
      the sprint number was observed for all cycle performance parameters (p<0.05). The
      main effect for the time of day was not significant for any biomechanical indices
      of neuromuscular performance. A significant interaction effect of the time of day
      and the sprint repetition was demonstrated on P (TCK) ( F(2,22)=4.3, p<0.05). The
      decrease in P (TCK) consecutive to sprint repetition was sharper in the evening
      compared to the morning (sprint 10[% of sprint 1]:-9.5 % in the evening vs. - 2.2
      % in the morning, p<0.05). Significant interaction effects of the time of day and
      the condition (i. e. pre, post, post 5) were also demonstrated for RMS (
      F(2,22)=3.6, p<0.05) and NME ( F(2,22)=4.5, p<0.05) during MVC. These
      interactions were characterised by similar patterns of fatigue occurrence (i. e.
      post vs. pre condition) in the morning (+7.5 % for RMS, - 19.6 % for NME) as in
      the evening (+10.2 % for RMS, -19.4 % for NME) but different patterns of short
      term recovery (i. e. post 5 vs. post condition; p<0.05) in the morning (-7.3 %
      for RMS, +13.7 % for NME) compared to the evening (+3.3 % for RMS, -1.8 % for
      NME). These results suggest that short-term recovery patterns of neuromuscular
      function are slower in the evening compared to the morning.

PMID- 16586327
TI  - Exercise mode affects the time to achieve VO2max without influencing maximal
      exercise time at the intensity associated with VO2max in triathletes.
AB  - The objective of this study was to analyze, in triathletes, the possible
      influence of the exercise mode (running x cycling) on time to exhaustion (TTE)
      and oxygen uptake (VO2) response during exercise performed at the intensity
      associated with the achievement of maximal oxygen uptake (IVO2max). Eleven male
      triathletes (21.8 +/- 3.8 yr) performed the following tests on different days on
      a motorized treadmill and on a cycle ergometer: 1) incremental tests in order to
      determine VO2max and IVO2max and, 2) constant work rate tests to exhaustion at
      IVO2max to determine TTE and to describe VO2 response (time to achieve VO2max -
      TAVO2max, and time maintained at VO2max-TMVO2max). No differences were found in
      VO2max, TTE and TMVO2max obtained on the treadmill tests (63.7 +/- 4.7 ml . kg (
      1) . min (-1); 324.6 +/- 109.1 s; 178.9 +/- 93.6 s) and cycle ergometer tests
      (61.4 +/- 4.5 ml . kg (- 1) . min (-1); 390.4 +/- 114.4 s; 213.5 +/- 102.4 s).
      However, TAVO2max was influenced by exercise mode (145.7 +/- 25.3 vs. 176.8 +/-
      20.1 s; in treadmill and cycle ergometer, respectively; p = 0.006). It is
      concluded that exercise modality affects the TAVO2max, without influencing TTE
      and TMVO2max during exercise at IVO2max in triathletes.

PMID- 16586328
TI  - Comparison of the type of substrate oxidation during exercise between pre and
      post pubertal markedly obese boys.
AB  - The aim of this study was to investigate, in markedly obese children, the effect
      of puberty on substrate oxidation during an acute bout of exercise. Two groups of
      markedly obese boys (7 pre pubertal, 8 post pubertal, matched for adiposity)
      performed an exercise-test designed for measuring carbohydrate and fat oxidation
      with indirect calorimetry, and consisting of five six-minute steady-state
      workloads at 20, 30, 40, 50, and 60 % of the theoretical maximal aerobic power.
      Fat oxidation (mg . min (-1)) is correlated to fat free mass (FFM) (r = 0.7, p =
      0.02). When expressed in crude flow rate units, fat oxidation is slightly higher
      in PostP than PreP children (p < 0.05). However, when expressed per unit of FFM
      or as a percentage of total fuel oxidation, fat oxidation is lower in PostP than
      PreP children (p < 0.05). Multivariable analysis shows that the influence of age
      on the ability to oxidize fat at exercise is explained by the pubertal increase
      in FFM. In markedly obese children during puberty, the ability of each kg of FFM
      to oxidize fat at exercise decreases (- 28% at 20%Wmax th), but the pubertal
      increase in FFM overcomes this effect, resulting in an increase in whole body
      ability to oxidize fat at exercise (+ 17,3% at 20%Wmax th).

PMID- 16586329
TI  - Effects of kayak ergometer training on motor performance in paraplegics.
AB  - The purpose of this study was to assess the effects of kayak ergometer training
      on functional tests performed in wheelchair by persons with spinal cord injury.
      Ten post-rehabilitated persons with thoracic spinal cord injury volunteered for
      the study and performed 30 sessions of kayak ergometer training during a 10-week
      period. The ergometer was modified with an additional balance demand in the medio
      lateral direction. Before and after the training period the subjects performed
      functional tests in the wheelchair: Sit-and-reach tests (distance), mounting a
      platform, transfer to a bench (height), propelling the wheelchair: 5 m on the
      rear wheels; in a figure-8; 15 m on a level surface and 50 m on a 3 degrees
      inclined surface (time). Test-retests were performed for all tests before the
      training began. A written questionnaire was distributed to evaluate the
      subjective experiences of the training. The test-retest resulted in coefficient
      of variation of 1.3 - 4.6 %. There were significant improvements in sit-and-reach
      (14 %), mounting a platform (7 %), transfer to a bench (10 %), propelling on
      level (3 %), and inclined surface (6 %). Furthermore, the training, did not cause
      any shoulder pain or other problems. This, and the positive subjective experience
      expressed by the subjects after the training indicate that this type of training
      is a suitable activity for persons with thoracic spinal cord injury.

PMID- 16586330
TI  - Brain serotonin reuptake did not change during one year in overtrained athletes.
AB  - Brain 5-HT neurotransmission has been described to be down-regulated in depressed
      people, and also suspected to be changed in overtraining state, the consequence
      of long-term physical overloading and stress in athletes. We studied brain
      serotonin (5-HT) transporter binding i.e., 5-HT reuptake with the specific
      radioligand (123-I-labelled 2beta-carbomethoxy-3beta[4-iodopenyl]-nortropane, Nor
      beta-CIT), and with single photon emission tomography (SPET) in severely
      overtrained athletes and their controls at the baseline and after a one-year
      recovery period. Twelve overtrained (6 women and 6 men, mean age 27 yrs, range 16
      - 39 yrs) and 11 healthy (6 women, 5 men, 26 yrs, 20 - 39 yrs) athletes were
      examined. Overtrained athletes 1) had suffered from an unexplained decrement in
      physical performance and fatigue for several weeks to many months and continued
      to have the same symptoms even after a recovery time of weeks to months, 2) had
      been examined to be otherwise healthy, and 3) had a suitable training history for
      overtraining. Nor-beta-CIT SPET was acquired 5 min, and 3, 6, and 24 h after the
      injection of the radioligand. 5-HT reuptake in ml/ml in midbrain (raphe nuclei)
      was calculated as (midbrain - cerebellum)/cerebellum. According to two-way
      analysis of variance, no changes inside the groups or group differences in 5-HT
      reuptake were found. Male athletes had significantly higher 5-HT reuptake than
      female athletes at the baseline (p = 0.034). The overtrained athletes were
      moderately depressed, while their scores in standardized Hamilton and Montgomery
      Asberg Depression Rating Scales were 16 +/- 2 (mean +/- SEM, range 8 - 29) and 17
      +/- 2 (7 - 28), respectively. In the CA, the scores were 6 +/- 1 (range 2 - 18)
      and 6 +/- 2 (1 - 19), respectively. 5-HT reuptake did not correlate with the
      depression scores either in the whole group or in the OA. The finding of the
      present study does not support the idea of long-term changes in 5-HT
      neurotransmission in overtraining state, in this case serotonin reuptake in
      midbrain, the regulating area of brain serotonin neurotransmission. Furthermore,
      depression of overtrained athletes may be its own variant having no correlation
      with 5-HT reuptake in midbrain. Sex may have effect on chronic stress response at
      the brain level in athletes, which may be a confusing factor in the overtraining
      studies, and has to be taken into consideration in the future.

PMID- 16586331
TI  - Short-term training is accompanied by a down regulation of ACC2 mRNA in skeletal
      muscle.
AB  - Recently, we showed that short-term training induced a rapid increase in IMCL
      whilst insulin sensitivity tended to improve. Here we investigate molecular
      adaptations accompanying this physiological training-induced accumulation of
      IMCL. Nine untrained men (age: 23.3 +/- 3.2 y; maximal power output: 3.8 +/- 0.6
      W/kg body weight) trained for two weeks. Before and after training, subjects
      cycled for three hours and biopsies were taken before and after exercise. mRNA
      concentrations of ACC2, HSL, LPL, Glut4 and HKII were quantified by RT-PCR and
      association of Glut4 with the membrane was quantified by immunohistochemical
      method. Endurance training resulted in a decrease of 29.1 % in ACC2 mRNA (p =
      0.02). After training, ACC2 mRNA tended to decrease with acute exercise (- 24.4 %
      [p = 0.06]). HSL mRNA decreased with acute exercise after training (- 37.3 % [p =
      0.002]). LPL mRNA concentrations increased with acute exercise before training (+
      42.4 % [p = 0.05]) and HKII mRNA increased with acute exercise before (+ 72.5 %
      [p = 0.025]) and after training (+ 99.3 % [p = 0.05]). After acute exercise, more
      Glut4 was associated with the membrane than before exercise, but it was not
      affected by training. We conclude that the training-induced increase in IMCL was
      accompanied by molecular adaptations in muscle to improve fat oxidative capacity,
      while markers of glucose metabolism were not yet changed. The present data are in
      line with the hypothesis that the fat oxidative capacity might be more important
      than the IMCL content in determining insulin sensitivity.

PMID- 16586332
TI  - Heart rate, thermoregulatory and humoral responses during a 9-day cycle race in a
      hot and humid climate.
AB  - Seven acclimated elite road cyclists were recruited from among the participants
      in the Tour de Guadeloupe, a 9-day cycle race (D1-D9) held in hot/humid climate
      (approximately 31 degrees C dry temperature and 76 % relative humidity). Each day
      of the competition, heart rate (HR) was recorded every 15 s, tympanic temperature
      (Ttym) was recorded before exercise and immediately at the end of each stage, and
      body mass loss (BML) was measured by changes in nude body mass at rest and after
      each stage. Blood lactate concentration [La] was measured at rest and 5 min after
      each stage. Venous blood samples were collected before the competition and on the
      4 th and 8 th days (D4, D8) for hematological and serum determinations and
      biochemical analyses. No significant differences were found in cardiac,
      thermoregulatory, or [La] parameters at rest over the 9 days. The subjects spent
      31 +/- 6 % of their time below the lactate threshold (LT), 52 +/- 8 % between LT
      and the onset of blood lactate accumulation (OBLA), and 18 +/- 6 % above OBLA.
      The increase in Ttym at D3 (0.48 +/- 0.3 degrees C) was significantly lower (p <
      0.05) than at D1, D4, D5, and D6. No difference was found for BML between the
      different stages. Significant increases (p < 0.05) were observed in monocytes at
      D8 vs. D4 and pre-race values (D0) and in serum Cl-concentration at D4 vs. D0 and
      D8 (p < 0.05). A significant reduction was observed in mean corpuscular
      hemoglobin concentration (MCHC) at D8 and D4 vs. D0 (p < 0.01). No difference was
      found in other blood parameters at D0, D4, or D8. Taken together, these results
      suggest that a consecutive 9-day cycle competition in hot/humid climate did not
      alter homeostasis at rest in acclimated well-trained cyclists. No major effect of
      repeated cycling stages on thermoregulatory and blood parameters was observed
      during the Tour de Guadeloupe. Further research is needed to compare the cardiac
      adaptations of natives to tropical climate and un-acclimated subjects during long
      duration exercise.

PMID- 16586333
TI  - Leg heating and cooling influences running stride parameters but not running
      economy.
AB  - To evaluate the effect of temperature on running economy (RE) and stride
      parameters in 10 trained male runners (VO2peak 60.8 +/- 6.8 ml . kg (-1) . min (
      1)), we used water immersion as a passive temperature manipulation to contrast
      localised pre-heating, pre-cooling, and thermoneutral interventions prior to
      running. Runners completed three 10-min treadmill runs at 70 % VO2peak following
      40 min of randomised leg immersion in water at 21.0 degrees C (cold), 34.6
      degrees C (thermoneutral), or 41.8 degrees C (hot). Treadmill runs were separated
      by 7 days. External respiratory gas exchange was measured for 30 s before and
      throughout the exercise and stride parameters were determined from video analysis
      in the sagittal plane. RE was not affected by prior heating or cooling with no
      difference in oxygen cost or energy expenditure between the temperature
      interventions (average VO2 3rd-10th min of exercise: C, 41.6 +/- 3.4 ml . kg (-1)
      . min (-1); TN, 41.6 +/- 3.0; H, 41.8 +/- 3.5; p = 0.94). Exercise heart rate was
      affected by temperature (H > TN > C; p < 0.001). During minutes 3 - 5 of running
      the respiratory-exchange and minute ventilation/oxygen consumption ratios were
      greater in cold compared with thermoneutral (p < 0.05). Averaged over the full 10
      min of exercise, stride length was shorter and stride frequency higher for the C
      trial compared to TN and H (p < 0.01). Leg temperature manipulation did not
      influence running economy despite changes in stride parameters that might
      indicate restricted muscle-tendon elasticity after pre-cooling. Larger changes in
      stride mechanics than those produced by the current temperature intervention are
      required to influence running economy.

PMID- 16586334
TI  - Non-linear analyses of heart rate variability during heavy exercise and recovery
      in cyclists.
AB  - We investigated the time course of RR interval variability during exercise and
      subsequent 50 minutes of recovery in seven well-trained male cyclists who
      performed an exercise with 3 successive 8 min stages at 40 %, 70 % and 90 % of
      their maximal oxygen uptake. The goal of the study was to check whether the
      decrease in the amplitude of heart rate variability during heavy exercise was
      accompanied by changes in the chaotic structure of the fluctuations. Heart rate
      variability was analysed in the temporal and frequency domain using traditional
      tools and using non-linear methods (Largest Lyapunov Exponent, Detrended
      Fluctuation Analysis, Minimum Embedding Dimension). When compared to rest,
      variability at the heaviest exercise intensity was significantly lower (RR: 0.94
      +/- 0.22 vs. 0.34 +/- 0.01 ms; SDRR: 0.11 +/- 0.04 vs. 0.01 +/- 0.00 ms) due to a
      decrease in both LF (2101 +/- 1450 vs. 0.14 +/- 0.09 ms (2) . Hz (-1)) and HF
      spectral energy (1148 +/- 1126 vs. 7.88 +/- 9.24 ms (2) . Hz (-1)). Non-linear
      analyses showed that heart rate variability remained chaotic whatever the
      exercise intensity (the largest Lyapunov exponent was positive at 90 % of the
      maximal oxygen uptake), with a fractal organisation that tended towards white
      noise (DFA value close to 0.5) during heavy exercise. During recovery, temporal
      and spectral variables came back to their rest values within about 30 minutes
      following an exponential pattern. Non-linear analyses revealed that heartbeat
      dynamics were disorganised at the beginning of recovery, and involved more
      regulating systems than at rest, even after 50 minutes of recovery. We concluded
      that, during heavy exercise, heart rate variability was mainly influenced by
      other factors than autonomous nervous system, and suggest that mechanical or
      neurological couplings between the cardiac, locomotor and respiratory systems
      could play an important part in the observed changes.

PMID- 16586335
TI  - Effect of exercise, body composition, and nutritional intake on bone parameters
      in male elite rock climbers.
AB  - A low body mass index is considered essential for high performance in rock
      climbing; however its effect on bone may be negative. In this study we compared
      the BMD of competitive male rock climbers (n = 20) and age- and BMI-matched non
      training controls (n = 11). Subjects with any medication or illness affecting
      bone metabolism or a family history of osteoporosis were not included in the
      analysis. Total body BMD was measured by dual-energy X-ray absorptiometry.
      Quantitative computed tomographic scans were made from the femoral neck and the
      lumbar spine. Dietary intake was assessed by a 5-day protocol. BMD of the TB-scan
      was significantly higher in the climbers group for all sub-regions except the
      skull (p = 0.191) and the lower extremities (p = 0.079). Trabecular and cortical
      BMD of the LS were significantly higher (p = 0.036 and p = 0.004) in the
      climbers. The same was true for total (p = 0.005) and cortical (p = 0.002) BMD of
      the FN. Trabecular BMD (p = 0.054), CSA (p < 0.343) and cortical thickness (p =
      0.065) of the FN was non-significantly higher for the climbers. Our study
      indicates that the effect of climbing on bone parameters PER SE is not
      detrimental in elite male athletes. Contrarily climbers demonstrated
      significantly higher BMD values at all loaded regions without "steal effects" at
      skeletal sites with low mechanical impact. Although we determined a moderately
      negative effect of low BMI on BMD we could not decide whether a low BMI value
      should be used as an exclusion criterion in high level climbing competitions as
      practized by the Austrian Sportclimbing Organization.

PMID- 16586336
TI  - Competition and food restriction effects on oxidative stress in judo.
AB  - We examined the effects of weight loss induced by restricting energy and fluid
      intake on antioxidant status and oxidative stress of judo athletes. Twenty male
      judoka were randomly assigned to one of two groups (Group A: called diet, n = 10;
      height 174.8 +/- 1.9 cm, body weight 75.9 +/- 3.1 kg; they were asked to lose
      approximately 5 % of their body weight through self-determined means during the
      week before the competition; Group B: called control, n = 10; height 176.4 +/-
      1.1 cm, body weight 73.3 +/- 6.3 kg maintained their body weight during the week
      before the competition). A battery of tests was performed during a baseline
      period (T1) on the morning of a simulated competition (T2) and 10 minutes after
      the end of the competition (T3). These tests included assessment for body
      composition, determination of lag phase (Lp) before free radical induced
      oxidation, maximum rate of oxidation (Rmax) during the propagating chain reaction
      and maximum amount of conjugated dienes (CDmax) accumulated after the propagation
      phase, and lipidic profile. Uric acid concentrations were also evaluated in
      plasma. Dietary data were collected using a 7-day diet record. We noted that the
      athletes followed a low carbohydrate diet whatever the period of the
      investigation. Concerning antioxidant nutrients, we can notice that mean
      nutritional intakes are in the normal range values for vitamin A, C and E at T1
      and T2. Rapid weight loss induced a significant increase in Lp values (p < 0.05)
      and uric acid concentrations without alterations in oxidative stress. Our data
      also showed that the competition induced the same changes of oxidative
      antioxidant status whatever the dietary intake during the seven days before the
      competition. Moreover, the effect of the competition on the antioxidant and
      oxidant parameters was more pronounced than the diet. Theses results could be
      linked to the food containing a large proportion of PUFA and a relative low
      proportion of carbohydrates.

PMID- 16586337
TI  - Distribution of caffeine levels in urine in different sports in relation to
      doping control before and after the removal of caffeine from the WADA doping
      list.
AB  - Caffeine concentrations were measured in the urine of 4633 athletes tested for
      doping control in the Ghent Doping Control Laboratory in 2004. Determination of
      these concentrations was done using an alkaline extraction with a mixture of
      dichloromethane and methanol (9 : 1; v/v) followed by high performance liquid
      chromatography and ultraviolet detection (HPLC-UV). The method was validated
      according to ISO 17 025 standards (International Organisation for
      Standardisation). Quantification was done by using a linear calibration curve in
      the range from 0 to 20 microg/ml. The limit of quantification (LOQ) was 0.10
      microg/ml. Because the results were not normally distributed, transformation of
      the data was done to evaluate the difference in detected concentrations in
      several sports. This resulted in an overall average concentration of 1.12 +/-
      2.68 microg/ml. Comparison of the most frequently tested sports in 2004
      demonstrated that caffeine concentrations in samples originating from power
      lifters are significantly higher in comparison to urines taken in other sports.
      Also, a significant difference between caffeine concentrations found in cycling
      and concentrations found in other sports, including athletics and some ball
      sports, was observed. A comparison was made between results obtained in 2004 and
      results obtained before the removal of caffeine from the WADA (World Anti-Doping
      Agency) doping list indicating that average caffeine concentrations decreased
      after the withdrawal of caffeine from the list of prohibited substances. The
      overall percentage of positive samples between the two periods remained the same
      although the percentage of positive samples noticed in cycling increased after
      the removal of caffeine from the doping list.

PMID- 16586338
TI  - Self-reported attitudes of elite athletes towards doping: differences between
      type of sport.
AB  - Although athletes' beliefs and values are known to influence whether or not an
      athlete will use banned drugs, little is known about the athletes' beliefs and
      attitudes in different sports. The aim of this study was to clarify the beliefs
      and attitudes of elite athletes towards banned substances and methods in sports.
      A total of 446 athletes (response rate 90.3 %; 446/494) financially supported by
      the National Finnish Olympic Committee completed a structured questionnaire
      during their national team camps in 2002. More than 90 % of the athletes reported
      to believe that banned substances and methods have performance enhancing effects,
      and 30 % reported that they personally know an athlete who uses banned
      substances. Of the male athletes 35 %, and 23 % of females reported they
      personally know an athlete using banned substances. A total of 15 % of the
      athletes reported that they had been offered banned substances: 21 % of the speed
      and power athletes, 14 % of the team sport athletes and of the athletes in motor
      skills demanding events, and 10 % of the endurance athletes. Stimulants were the
      most often offered substance group (to 7 % of all the athletes) followed by
      anabolic steroids (4 %). Subjects who regarded doping as a minor health risk
      seemed to be more often associated with doping users than those regarding doping
      as a significant health risk. Athletes in different sports have a different
      approach to doping. Risk of doping appears to be highest in speed and power
      sports and lowest in motor skills demanding sports. Males are at higher risk than
      females. Controlling doping only by tests is not sufficient. A profound change in
      the attitudes is needed, which should be monitored repeatedly.

PMID- 16586339
TI  - Sports exercise effect on shortening of saccadic reaction time associated with
      neck extensor muscle activity.
AB  - We investigated sports exercise effect on shortening of saccadic reaction time
      associated with neck extensor muscle activity. Saccadic reaction time was
      measured in neck rest position, 20 degrees neck flexion, and 30 % muscle
      contraction of the shoulder girdle elevators for two groups. These groups were an
      untrained group that has never belonged to any sports club (UT group) and a group
      that has belonged to high-speed ball sports clubs (HS group). In the neck flexion
      and 30 % muscle contraction conditions, there was a significant shortening of the
      reaction time for the HS group. For the UT group, no significant shortening was
      found in those conditions, and the reaction time in the 30 % contraction was
      rather significantly longer than that in the rest position. Sports experience
      pursuing a high-speed ball will be effective in the shortening of the saccadic
      reaction time associated with the activity of neck extensors.

PMID- 16586340
TI  - Reproducibility of time at or near VO2max during intermittent treadmill running.
AB  - The purpose of this study was to determine the reproducibility of time at or
      above 90 % (t (90 % )VO (2max)) and 95 % (t (95 % )VO (2max)) maximal oxygen
      uptake during an intermittent treadmill run to exhaustion. Twenty-two distance
      runners (age 38.0 +/- 7.1 yrs) performed two identical incremental and two
      identical intermittent tests on four separate days. Respiratory exchange was
      measured continuously throughout each test by an automated open-circuit gas
      analysis system. The incremental test consisted of increases in treadmill speed
      every minute until volitional exhaustion. The highest averaged 30-s oxygen uptake
      (VO (2)) value was defined as VO (2max) and the minimum speed that elicited VO
      (2max) was defined as vVO (2max). The intermittent test consisted of 30-s work
      intervals ran at 105 % vVO (2max) interspersed by 30-s relief intervals ran at 60
      % vVO (2max) and was continued until volitional exhaustion. The time that VO (2)
      was at or above 90 % and 95 % of the mean maximum values elicited during the two
      previous incremental tests was determined for the intermittent tests. The mean t
      (95 % )VO (2max) was 232 (SD 174) s and 244 (SD 195) s and the mean t (90 % )VO
      (2max) was 480 (SD 220) s and 488 (SD 252) s, for trial 1 and trial 2,
      respectively. Reproducibility statistics for t (95 % )VO (2max) and t (90 % )VO
      (2max), respectively, were: 95 % limits of agreement 12 +/- 227 s and 8 +/- 328
      s; coefficient of variation 34.5 % and 24.5 %; and intraclass correlation
      coefficient 0.80 and 0.75. Statistical power analysis indicated that this level
      of reproducibility would allow mean differences of 15 - 20 % between intermittent
      training protocols to attain statistical significance in future experimental
      research, with sample sizes probably within the resources of most researchers.

PMID- 16586341
TI  - The 24 h urinary cortisol/cortisone ratio and epinephrine/norepinephrine ratio
      for monitoring training in young female tennis players.
AB  - The effect of training variations on the 24 h urinary cortisol/cortisone (C/Cn)
      ratio and the epinephrine/norepinephrine (E/NE) ratio in relation with mood
      (evaluated using the Brunel Mood Scale: BRUMS) and performance was investigated
      in seven trained young female tennis players (12.8 +/- 1.7 years). Like the
      proposed model in adults, the monitoring of hormonal and mood parameters could be
      a useful index in training follow-up in young sportswomen. Assessment of
      nutritional intake, nitrogen excretion rate and nitrogen balance were also
      determined to measure the dietary practice of these athletes. Nitrogen balance
      was calculated from the mean daily protein intake and the urinary nitrogen
      excretion. Data were collected after a 1-month rest (September, T1), 3 months
      after T1 (after technical and endurance training: December, T2) and 7 months
      after T1 (after 4 months of increasing-volume/high-intensity training: March,
      T3). A significant increase in C/Cn ratio (+ 30 %, p < 0.05) were noted from T1
      to T3. In the same time, urinary NE concentrations decreased significantly. The
      E/NE ratio increased from T1 to T2 and decreased at T3 (T1 vs. T3: - 30 %, p <
      0.05). The BRUMS inventory at T3 reflected changes in specific mood states with a
      significant increase in fatigue and anger scores, while vigor scores decreased
      significantly compared to T1. This period also corresponded with the lowest
      percentage of matches won and with the highest training load. Energy intake was
      about 16 % lower than the French recommendations for girls of the same age.
      However, a positive nitrogen balance was observed from a mean intake of 1.0 g x
      kg (-1) x day (-1). Our results reveal that an increase of overnight urinary C/Cn
      ratio and a decrease of E/NE ratio are concomitant with alterations in mood state
      and performance, all these parameters being associated with physical and
      psychological stress.

PMID- 16586342
TI  - Ample use of physician-prescribed medications in Finnish elite athletes.
AB  - The present study aimed at determining the use of physician-prescribed medication
      in a large number of elite athletes compared with a representative control sample
      of the general population. Of all the athletes (N = 494) financially supported by
      the National Olympic Committee, 446 completed a structured questionnaire
      (response rate 90.3 %) in 2002. A control group (N = 1503, response rate 80.1 %)
      comprised an age-matched sample from the population-based study collected by the
      National Public Health Institute. Any prescribed medication was used by 34.5 % of
      the athletes and 24.9 % of the controls during the past seven days. The most
      frequently reported physician-prescribed medications among athletes during the
      previous seven days were anti-allergic medicines (12.6 % of the respondents), non
      steroidal anti-inflammatory drugs (NSAIDs; 8.1 %), anti-asthmatic medicines (7.0
      %), and oral antibiotics (2.7 %). The adjusted odds ratios (95 % CI) for the
      physician-prescribed medications used during the previous seven days was 2.42
      (1.69 - 3.46), 3.63 (2.25 - 5.84), 3.42 (2.05 - 5.70), and 2.15 (1.03 - 4.45) for
      use of anti-allergic medication, NSAIDs, anti-asthmatic medication, and oral
      antibiotics, respectively, in the athletes compared with controls. Every fifth
      athlete reported some NSAID-related adverse effect. In conclusion, the athletes
      used NSAIDs, antibiotics, anti-asthmatic and anti-allergic medication
      significantly more often than a representative sample of age-matched controls.
      All these medicines have potential adverse effects that may have a deleterious
      impact on the maximum exercise performance of elite athletes. Adverse effects
      were commonly reported in connection with NSAID use.

PMID- 16586343
TI  - Salivary IgA response to intermittent and continuous exercise.
AB  - Current evidence would support a view that intense exercise increases whereas
      moderate exercise reduces the susceptibility to illness, predominately upper
      respiratory tract infections. Concentrations of IgA and cortisol in saliva may be
      used to reflect changes in immune function. The aim of this study was to
      determine if the type of exercise (soccer-specific intermittent or continuous
      exercise at the same average work-rate and duration) affects salivary IgA (s-IgA)
      and cortisol responses. In a randomized, counterbalanced design, eight healthy
      males completed two trials one week apart at the same time of day on a motorized
      treadmill. One session entailed soccer-specific intermittent exercise, the other
      involved continuous exercise at the same overall work-rate. Diet and activity
      were standardized for 48 hours prior to and following each trial. Unstimulated
      saliva samples were collected via passive expectoration during the week prior to
      commencement of exercise, before, at half-time, immediately post-exercise, and 6
      hours, 24 hours, and 48 hours post-exercise. No significant difference was
      observed in heart rate between the two exercise conditions (Intermittent: 142 +/-
      14; Continuous: 141 +/- 16 beats x min (-1)). Average rating of perceived
      exertion was higher (p < 0.05) in intermittent exercise (11.9 +/- 0.8) than
      during continuous exercise (10.8 +/- 1.2). The pattern of change in salivary
      responses, including solute secretion rate, IgA concentration, IgA secretion
      rate, IgA to osmolality ratio, cortisol, and cortisol secretion rate did not
      differ between the two trials (p > 0.05). Concentrations of s-IgA for the
      intermittent and continuous protocols were 131.6 +/- 61.2 vs. 146.4 +/- 107.6
      before, 148.4 +/- 82.5 vs. 229.2 +/- 159.6 after, and 125 +/- 78.7 vs. 131.1 +/-
      80.7 48 h post-exercise, respectively. Saliva flow rate decreased and osmolality
      increased significantly across all time points (p < 0.05). In conclusion, soccer
      specific intermittent exercise did not suppress the salivary IgA response or
      alter cortisol secretion compared to continuous exercise performed at the same
      overall work-rate.

PMID- 16586344
TI  - August Rauber (1841-1917): from the primitive streak to Cellularmechanik.
AB  - In the early 19th century Karl Ernst von Baer initiated a new research program
      searching for the mechanisms by which an egg transforms itself into an embryo.
      August Rauber (1841-1917) took up this challenge. He considered the phylogenetic
      principle as the right tool to explain the similitude of embryogenetic processes.
      In extending Baer's approach, he combined comparative embryology and histology in
      his studies of avian and mammalian embryos. His earlier work demonstrated that
      the two-layered chick embryo is a modified gastrula and not a "disc" as Wilhelm
      His had claimed. From the 1880s onwards, he concentrated on the issue of how the
      development of germ layers is related to tissue differentiation. To address this,
      he studied the blastopore, epiblast, primitive streak, teratology and the
      relative importance of nucleus and cytoplasm in heredity. This paper reconstructs
      some of Rauber's work and concludes that his observations and reflections
      constituted a new approach combining embryology and histology with "phylogenetic"
      reasoning.

PMID- 16586345
TI  - Evolutionary embryology resurrected in Japan with a new molecular basis: Nori
      Satoh and the history of ascidian studies originating in Kyoto during the 20th
      century.
AB  - This article briefly summarizes the scientific contributions of Nori Satoh, the
      winner of the 2005 edition of the Kowalevsky Medal, to Developmental Biology and
      especially to Evo-Devo with his 30 years of research on tunicates - a primitive
      chordate species. His research began with his pure developmental interest in the
      clock mechanism of cell differentiation and later expanded into various aspects
      of evolutionary and developmental phenomena. He is not only known as a founder of
      molecular biology-based tunicate studies, but also for his world-wide service to
      education and his prestigious publications in international scientific journals.

PMID- 16586346
TI  - Dynamic distribution of the replacement histone variant H3.3 in the mouse oocyte
      and preimplantation embryos.
AB  - Upon fertilization, the gametes undergo a drastic reprogramming that includes
      changes in DNA methylation and histone modifications. Currently, it is not known
      whether replacement of the major histones by histone variants is also involved in
      these processes. Here we have examined the expression and localization of the
      histone variant H3.3 in early mouse embryogenesis. We show that H3.3 is present
      in the oocyte as a maternal factor. It is then incorporated preferentially into
      the male pronucleus before genome activation, pointing towards an asymmetry in
      histone composition between the two pronuclei. This is in line with the male
      pronucleus bearing transcriptional activation first. The same distribution was
      observed when we followed the localisation of a tagged version of H3.3. We
      detected H3.3 in the nuclei of mouse embryos in all of the stages analysed, from
      the zygote to the blastocyst stage, suggesting that the epigenetic mechanisms in
      the early embryo not only involve changes in histone modifications but may also
      include histone replacement.

PMID- 16586347
TI  - Two modes of action by which Xenopus hairy2b establishes tissue demarcation in
      the Spemann-Mangold organizer.
AB  - The Hairy and Enhancer-of-Split (HES) family of transcriptional repressors plays
      important roles in pattern formation during development throughout the animal
      kingdom. Generally, HES proteins repress the expression of genes specific for
      neighboring tissues to maintain the nature of cells expressing HES proteins,
      resulting in pattern formation. Xhairy2b, a Xenopus HES, establishes the
      prospective anterior prechordal mesoderm identity in the Spemann-Mangold
      organizer by both inducing specific genes and repressing the genes specific for
      neighboring tissues. Here we report that Xhairy2b has two modes of action, each
      of which corresponds to inductive and repressive functions. We show that the
      inductive function is independent of direct transcriptional regulation and is
      exhibited by the C-terminal WRPW tetrapeptide motif alone, although it induces
      the expression of a wide variety of the organizer genes that Xhairy2b represses.
      The transcriptional repression by Xhairy2b is responsible for only the repressive
      function. We propose that the activity of the WRPW motif intrinsically induces
      the expression of genes specific for the organizer in a rather non-specific
      manner to ensure the organizer environment. Then, the transcriptional repression
      selectively down-regulates the expression of some of these genes, resulting in
      the regionalization of the axial mesoderm. Our study provides new insight into
      how a region of the vertebrate embryo is demarcated by one dual-functional
      transcription factor in the early stages of development.

PMID- 16586348
TI  - Bowline, a novel protein localized to the presomitic mesoderm, interacts with
      Groucho/TLE in Xenopus.
AB  - Cells in the prospective somite of Xenopus laevis embryos rotate in an
      orchestrated manner to form a segregated somite. The prospective somite
      boundaries are prepatterned by gene expressions in the unsegmented presomitic
      mesoderm (PSM). However, the roles of polarized gene expression in this boundary
      formation are not well elucidated. Here we identified a novel gene, bowline,
      which localizes to the anterior halves of S-II, III in the PSM of X. laevis.
      Bowline associated with corepressor XGrg-4, a Xenopus homolog of Groucho/TLE
      protein. A WRPW tetrapeptide motif in Bowline was prerequisite for
      coprecipitation with XGrg-4 and for downregulation of X-Delta-2 by bowline RNA
      injection. This study indicates that Bowline is a novel protein interacting with
      Groucho/TLE and may play a role in somitogenesis in X. laevis.

PMID- 16586349
TI  - Proliferation and apoptosis in early molar morphogenesis-- voles as models in
      odontogenesis.
AB  - Proliferation and apoptosis play crucial roles in the development of
      multicellular organisms. Their precise balance is necessary for tissue
      homeostasis throughout life. The developing dentition is a suitable model to
      study proliferation and apoptosis during embryogenesis, but the corresponding
      studies have been carried out principally in the mouse. The present study aimed
      to examine proliferation and apoptosis in the vole (Microtus sp., Rodentia)
      during the early morphogenesis of the first upper molar and compare it to what is
      known from the mouse. To this end, apoptosis and proliferation were investigated
      using histology and computer-aided 3D reconstruction. Mitoses accumulated
      predominantly in the developing cervical loop. Apoptosis during early
      odontogenesis showed highly specific spatio-temporal patterns in the dental
      epithelium. Apoptotic bodies were localised in non-dividing cell populations.
      They accumulated in the same places as described in the mouse: antemolar vestiges
      (ED 12.5 15.5), enamel knot (ED 14.5 15.5), stalk and palatally along the whole
      first molar tooth germ longitudinal axis (ED 15 - 15.5). Early tooth development
      in the field vole, including the distribution of apoptosis and mitosis, is very
      similar to that reported in the mouse, with the exception of the antemolar
      region. The microtine antemolar vestige is preserved longer than the murine one.
      It is conceivable that additional distinct differences in morphogenetic processes
      appear later in tooth development.

PMID- 16586350
TI  - Molar tooth development in caspase-3 deficient mice.
AB  - Tooth morphogenesis is accompanied by apoptotic events which show restricted
      temporospatial patterns suggesting multiple roles in odontogenesis. Dental
      apoptosis seems to be caspase dependent and caspase-3 has been shown to be
      activated during dental apoptosis.Caspase-3 mutant mice on different genetic
      backgrounds were used to investigate alterations in dental apoptosis and molar
      tooth morphogenesis. Mouse embryos at E15.5 were analyzed to reveal any changes
      in enamel knots, which are transient structures eliminated by apoptosis. In
      caspase-3(-/-) mice on the B57BL/6 background, disorganization of the epithelium
      was found in the original primary enamel knot area and confirmed by altered
      expression of Shh. Despite this early defect in molar tooth development, these
      mutants showed correct formation of secondary enamel knots as indicated by Fgf-4
      expression. Analyses of adult molar teeth did not reveal any major alterations in
      tooth shape, enamel structure or pattern when compared to heterozygote
      littermates. In caspase-3(-/-) mice on the 129X1/SvJ background, no defects in
      tooth development were found except the position of the upper molars which
      developed more posteriorly in the oral cavity. This is likely, however, to be a
      secondary defect caused by a physical squashing of the face by the malformed
      brain. The results suggest that although caspase-3 becomes activated and may be
      essential for dental apoptosis, it does not seem fundamental for formation of
      normal mineralised molar teeth.

PMID- 16586351
TI  - Msx1 and Msx2 have shared essential functions in neural crest but may be
      dispensable in epidermis and axis formation in Xenopus.
AB  - The homeodomain factors Msx1 and Msx2 are expressed in essentially identical
      patterns in the epidermis and neural crest of Xenopus embryos during neurula
      stages. Disruption of Msx1 and Msx2 RNA splicing with antisense morpholino
      oligonucleotides shows that both factors are also required for expression of the
      neural crest gene Slug. Loss of Msx1 can be compensated by overexpression of Msx2
      and vice versa. Loss of Msx factors also leads to alterations in the expression
      boundaries for neural and epidermal genes, but does not prevent or reduce
      expression of epidermal keratin in ventrolateral ectoderm, nor is there a
      detectable effect on dorsal mesodermal marker gene expression. These results
      indicate that Msx1 and Msx2 are both essential for neural crest development, but
      that the two genes have the same function in this tissue. If Msx genes have
      important functions in epidermis or axial mesoderm induction, these functions
      must be shared with other regulatory proteins.

PMID- 16586352
TI  - Tbx1 is expressed at multiple sites of epithelial-mesenchymal interaction during
      early development of the facial complex.
AB  - TBX1 encodes a T-box-containing transcription factor, which is thought to be a
      key player in the aetiology of the DiGeorge and Velocardiofacial syndromes
      (DGS/VCFS). In addition to defects affecting structures derived from the
      pharyngeal pouches, these patients exhibit varying degrees of facial
      dysmorphology and cleft palate. We have analysed the expression of murine Tbx1
      during early facial development and found transcripts at sites of known
      epithelial-mesenchymal interaction. In particular, Tbx1 was expressed in
      epithelium of the early facial processes, including the fronto-nasal, medial and
      lateral nasal and palatine. Transcripts were also localised to the epithelium of
      developing tooth germs and hair follicles at several stages during their early
      development. Together, these expression domains suggest a role for Tbx1 in
      mediating epithelial-mesenchymal signalling in regions of the developing face, a
      finding which is consistent with the spectrum of facial deformity encountered
      amongst subjects affected by DGS/VCFS.

PMID- 16586353
TI  - Protease inhibitor use during pregnancy: is there an obstetrical risk?

PMID- 16586354
TI  - Is antiretroviral therapy during pregnancy associated with an increased risk of
      preterm delivery, low birth weight, or stillbirth?
AB  - BACKGROUND: Data on complications of pregnancy associated with antiretroviral
      therapy are limited. Some small studies have demonstrated an increased preterm
      delivery rate, but a recent retrospective United States multisite study did not
      concur with these findings. Our objective was to investigate whether
      antiretroviral therapy was associated with adverse pregnancy outcome at a single
      site. METHODS: Using prospectively gathered data, women were identified who were
      determined to be human immunodeficiency virus positive before or during pregnancy
      who sought care at our prenatal clinic and who gave birth at the University of
      Miami/Jackson Memorial Medical Center from 1990 through 2002. The outcome
      measures were preterm delivery, low birth weight, and stillbirth. RESULTS: The
      cohort included 999 women who received antiretroviral therapy during pregnancy
      (monotherapy in 492, combination therapy without a protease inhibitor [PI] in
      373, and combination therapy with a PI in 134) and 338 women who did not receive
      therapy. After adjustment for possible confounders, only combination therapy with
      a PI was associated with an increased risk of preterm delivery, compared with any
      other combination (odds ratio, 1.8 [95% confidence interval, 1.1-3.0]). There
      were no differences in rates of low birth weight and stillbirth, regardless of
      therapy. CONCLUSION: Compared with monotherapy and combination therapy without a
      PI, only combination therapy with a PI was associated with an increased risk of
      preterm delivery.

PMID- 16586355
TI  - Evaluating the impact of hepatitis C virus (HCV) on highly active antiretroviral
      therapy-mediated immune responses in HCV/HIV-coinfected women: role of HCV on
      expression of primed/memory T cells.
AB  - OBJECTIVE: To evaluate the impact of hepatitis C virus (HCV) on the immune system
      before receipt of highly active antiretroviral therapy (HAART) and on immune
      recovery after receipt of HAART among human immunodeficiency virus (HIV)/HCV
      coinfected women enrolled in the Women's Interagency HIV Study. METHODS: The
      study included 294 HIV-infected women who initiated HAART and attended 2 follow
      up visits. The women were grouped on the basis of positive HCV antibody and HCV
      RNA tests. There were 148 women who were HCV antibody negative, 34 who were HCV
      antibody positive but RNA negative, and 112 who were HCV antibody and RNA
      positive. Immune recovery was measured by flow-cytometric assessment for markers
      of activation and maturation on CD4+ and CD8+ T cells. Data analysis used
      repeated measures of variance.Results. HIV/HCV coinfection is associated with an
      increased number of CD4+ and CD8+ primed/memory T cells. HIV/HCV coinfection,
      however, did not affect any further decreases in CD4+ or CD4+ and CD8+
      naive/memory T cell counts or enhanced T cell activation. HIV/HCV coinfection
      also did not affect HAART responses in the CD4+ and CD8+ T cell compartment.
      CONCLUSIONS: HCV does not affect immune responses to HAART in HIV/HCV-coinfected
      individuals but is associated with an expansion of CD4+ and CD8+ memory T cell
      subsets. Functional impairment in the CD4+ and CD8+ T cell compartments still
      needs to be assessed in coinfected patients.

PMID- 16586356
TI  - HIV infection and antiretroviral therapy: effect on hepatitis C virus
      quasispecies variability.
AB  - BACKGROUND: Hepatitis C virus (HCV) quasispecies variability has been associated
      with liver disease progression. The effects of human immunodeficiency virus (HIV)
      coinfection and highly active antiretroviral therapy (HAART) on HCV quasispecies
      variability have not been firmly established. METHODS: We determined HCV
      quasispecies complexity and diversity in 69 subjects, 28 of whom were HIV
      infected, using clonal frequency analysis via heteroduplex mobility analysis of
      the second envelope gene hypervariable region. Nucleotide sequencing was
      performed for a small subset of subjects. RESULTS: HIV-positive, HAART-naive
      subjects had significantly lower HCV quasispecies complexity and diversity than
      did both HIV-negative and HIV-positive HAART-treated subjects. In multivariate
      analysis, HIV infection predicted decreased complexity (P < .0001) and diversity
      (P = .001) of HCV quasispecies, whereas HAART predicted increased complexity (P =
      .013) and diversity (P = .026). For 4 of 6 patients, sequence analysis yielded
      data supporting the model that positive host pressure drives HCV quasispecies
      heterogeneity, although data favoring the hypothesis of selective outgrowth of
      the most fit variants were also observed. CONCLUSION: HIV coinfection is
      associated with decreased HCV quasispecies variability, which appears to be
      reversed by effective HAART. Although HIV- and HAART-related effects on host
      immune pressure are likely to play a role in the observed differences in HCV
      genetic heterogeneity, other mechanisms may be operative.

PMID- 16586357
TI  - Frequency and treatment-related predictors of thymidine-analogue mutation
      patterns in HIV-1 isolates after unsuccessful antiretroviral therapy.
AB  - We investigated, in patients tested between 1991 and 2004, the patterns of
      mutually exclusive human immunodeficiency virus-1 thymidine-analogue mutations
      (TAMs) in 4039 reverse-transcriptase sequences with > or = 1 TAM. TAM pattern 1,
      which included M41L and L210W and excluded K70R and is coupled with more
      extensive cross-resistance to drugs, became the most frequent pattern after 1996.
      In 1465 genotypes from 684 patients in whom highly active antiretroviral therapy
      (HAART) was unsuccessful, predictors of this pattern were the number of previous
      HAART regimens undergone (adjusted odds ratio [OR], 1.09 [95% confidence interval
      {CI}, 1.02-1.16]), use of stavudine/lamivudine (adjusted OR, 1.42 [95% CI, 1.05
      1.99]), use of nevirapine (adjusted OR, 1.60 [95% CI, 1.14-2.24]), use of
      efavirenz (adjusted OR, 1.56 [95% CI, 1.08-2.27]), and use of ritonavir (adjusted
      OR, 1.35 [95% CI, 1.04-1.75]).

PMID- 16586358
TI  - Dose-related safety and immunogenicity of a trivalent baculovirus-expressed
      influenza-virus hemagglutinin vaccine in elderly adults.
AB  - BACKGROUND: Influenza-virus hemagglutinin (HA) protein expressed in insect cells
      by recombinant baculovirus is a candidate influenza vaccine. METHODS: In a
      randomized, double-blind trial conducted in 399 adults > or = 65 years of age,
      the efficacy of trivalent inactivated influenza vaccine (TIV) licensed for
      intramuscular injection was compared with that of trivalent baculovirus-expressed
      HA vaccine administered at doses of 15 microg, 45 microg, or 135 microg of each
      HA. RESULTS: Compared with TIV, baculovirus-expressed HA vaccine was safe and
      induced better serum antibody responses to the H3 component when administered at
      doses of 45 microg or 135 microg of each HA. CONCLUSIONS: Baculovirus-expressed
      HA is a safe and immunogenic influenza vaccine in elderly adults.

PMID- 16586359
TI  - Clinical features of influenza C virus infection in children.
AB  - BACKGROUND: Seroepidemiological studies have revealed that influenza C virus is
      widely distributed globally. However, because the isolation of this virus is
      difficult, there have been few reports on its clinical features. METHODS: Between
      December 1990 and November 2004, 84,946 respiratory-tract specimens were obtained
      from patients < or = 15 years old. On the basis of the results of isolation of
      virus, we examined the clinical data on children infected with influenza C virus.
      RESULTS: Of 170 children infected with influenza C virus, 157 (92.4%) were < 6
      years old. Fever (frequency, 90.0%), cough (frequency, 74.1%), and rhinorrhea
      (frequency, 61.8%) were the most frequent symptoms. The mean duration of fever
      was 2.88 days (standard deviation, 1.66 days). Of the 170 children, 29 were
      hospitalized, and 21 (72.4%) of these 29 had lower-respiratory-tract illness such
      as pneumonia, bronchitis, and bronchiolitis. The rate of hospital admission was
      significantly higher in children < 2 years old than in children 2-5 years old
      (30.4% vs. 11.9%; P = .0043). CONCLUSIONS: Influenza C virus is a significant
      cause of upper-respiratory-tract illness in children < 6 years old, and the risk
      of complications with lower-respiratory-tract illness is particularly high in
      children < 2 years old.

PMID- 16586360
TI  - Pneumococcal coinfection with human metapneumovirus.
AB  - BACKGROUND: Infection with the newly discovered human metapneumovirus (hMPV) may
      lead to hospitalization of children with lower respiratory tract infection
      (LRTI), although the pathogenesis thereof remains to be elucidated. METHODS: This
      hypothesis-generating study involved a cohort of children randomized to receive 9
      valent conjugate pneumococcal vaccine or placebo and who were tested for hMPV
      infection when hospitalized for LRTI. By use of a nested reverse-transcription
      polymerase chain reaction assay targeted at amplifying a fragment of the hMPV
      fusion (F) protein gene, 202 such infections were identified among 2715 episodes
      of LRTI in children. RESULTS: Among human immunodeficiency virus (HIV)-uninfected
      children who had received 3 doses of conjugate pneumococcal vaccine, the
      incidence of hMPV-associated LRTI was reduced by 45% (95% confidence interval
      [CI], 19%-62%; P = .002), and the incidence of clinical pneumonia was reduced by
      55% (95% CI, 22%-74%; P = .003). Similarly, in fully vaccinated HIV-infected
      children, the incidence of hMPV-associated LRTI was reduced by 53% (95% CI, 3%
      77%; P = .035), and that of clinical pneumonia was reduced by 65% (95% CI, 19%
      85%; P = .020). CONCLUSIONS: The pathogenesis of hMPV-associated LRTI that
      results in hospitalization of both HIV-infected and -uninfected children involves
      bacterial coinfection with pneumococcus, and a significant proportion of these
      hospitalizations may be prevented by vaccination with pneumococcal conjugate
      vaccine.

PMID- 16586361
TI  - Anti-severe acute respiratory syndrome coronavirus immune responses: the role
      played by V gamma 9V delta 2 T cells.
AB  - Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS
      CoV) strain. Analyses of T cell repertoires in health care workers who survived
      SARS-CoV infection during the 2003 outbreak revealed that their effector memory V
      gamma 9V delta 2 T cell populations were selectively expanded ~3 months after the
      onset of disease. No such expansion of their alpha beta T cell pools was
      detected. The expansion of the V gamma 9V delta 2 T cell population was
      associated with higher anti-SARS-CoV immunoglobulin G titers. In addition, in
      vitro experiments demonstrated that stimulated V gamma 9V delta 2 T cells display
      an interferon- gamma -dependent anti-SARS-CoV activity and are able to directly
      kill SARS-CoV-infected target cells. These findings are compatible with the
      possibility that V gamma 9V delta 2 T cells play a protective role during SARS.

PMID- 16586362
TI  - Molecular evidence for mother-to-child transmission of Kaposi sarcoma-associated
      herpesvirus in Uganda and K1 gene evolution within the host.
AB  - BACKGROUND: Epidemiological studies of Kaposi sarcoma (KS)-related herpesvirus
      (KSHV) indicate that having a KSHV-seropositive mother is a risk factor for KSHV
      infection in children. METHODS: We determined the KSHV K1 sequences in
      concordantly polymerase chain reaction-positive Ugandan mother-child pairs, to
      ascertain whether they shared the same viral strain. We also examined sequences
      amplified from saliva and buffy coat samples from the same subjects, to
      investigate potential intrasubject sequence differences. RESULTS: We obtained K1
      sequences from 6 of 10 mother-child pairs. In 1 pair, the subtypes differed
      between mother and child. The mother and child in 2 other pairs shared the same
      subtype, but the sequences differed. The mother and child in 2 pairs shared KSHV
      strains with exact (100%) nucleotide homology. The last pair showed evidence of
      viral strain concordance between mother and child but also showed evidence of
      evolution of the viral sequence within the child. Of 26 study subjects, 19 showed
      no evidence of intrasubject K1 sequence variability, but, in 7 subjects, all of
      whom were children, amino acid variation of 1%-4% was observed. CONCLUSIONS: Our
      findings are consistent with KSHV transmission from maternal and nonmaternal
      sources in KS-endemic regions. Our results also provide evidence for ongoing
      evolution of the K1 gene in KSHV-infected children.

PMID- 16586363
TI  - Role of hepatitis B viral load and basal core promoter mutation in hepatocellular
      carcinoma in hepatitis B carriers.
AB  - BACKGROUND: Several hepatitis B viral factors correlate with the progression of
      chronic liver disease. However, the independent and interactive effects of each
      known viral factor on the development of hepatocellular carcinoma (HCC) remain
      largely unknown. METHODS: In a cross-sectional, retrospective, hospital-based
      setting, we comprehensively compared viral factors in 160 chronic hepatitis B
      virus (HBV) carriers and 200 patients with HCC, to clarify the independent and
      joint effect of each factor. RESULTS: In univariate analysis, statistically
      significant odds ratios (ORs) were obtained for male sex (P < .001), advanced age
      (P < .001), HBV genotype C infection (P = .005), the precore A1896 mutation (P <
      .001), and the basal core promoter (BCP) T1762/A1764 mutation (P < .001).
      According to the results of multiple logistic-regression analysis, advanced age,
      male sex, the precore A1896 mutation, the BCP T1762/A1764 mutation, and an HBV
      load > or = 10(5) copies/mL were independently associated with the development of
      HCC. Compared with patients with an HBV load < 10(5) copies/mL and the BCP
      A1762/G1764 wild-type strain, the adjusted OR of developing HCC was > or = 30 in
      patients with an HBV load > or = 10(5) copies/mL and the BCP T1762/A1764 mutant,
      irrespective of the presence of the precore A1896 mutation and viral genotype.
      CONCLUSIONS: HBV load and the BCP T1762/A1764 mutation are important in
      hepatocarcinogenesis.

PMID- 16586364
TI  - Antigenic shift and increased incidence of meningococcal disease.
AB  - BACKGROUND: The incidence of serogroup C and Y meningococcal disease increased in
      the United States during the 1990s. The cyclical nature of endemic meningococcal
      disease remains unexplained. The purpose of this study was to investigate the
      mechanisms associated with the increase in the incidence of meningococcal
      disease. METHODS: We characterized an increasing incidence of invasive serogroup
      C and Y meningococcal disease using population-based surveillance from 1992
      through 2001. Isolates were characterized by multilocus sequence typing and
      antigen sequence typing of 3 outer membrane protein (OMP) genes: porA variable
      regions (VRs) 1 and 2, porB, and fetA VR. RESULTS: For both serogroups, OMP
      antigenic shifts were associated with increased incidence of meningococcal
      disease. For serogroup Y, antigenic shift occurred through amino acid
      substitutions at all 3 OMPs--PorA VR 1 and 2, PorB, and FetA VR. For serogroup C,
      antigenic shift involved amino acid substitutions at FetA VR and, in some cases,
      deletion of the porA gene. On the basis of deduced amino acid sequences, the
      antigenic changes likely occurred by horizontal gene transfer. CONCLUSIONS:
      Antigenic shifts were associated with increased incidence of serogroup C and
      serogroup Y meningococcal disease. For serogroup Y, the changes involved all OMP
      genes that were studied. Increases in the incidence of meningococcal disease may
      be caused, in part, by antigenic shift.

PMID- 16586365
TI  - Staphylococcus aureus carriers neutralize superantigens by antibodies specific
      for their colonizing strain: a potential explanation for their improved prognosis
      in severe sepsis.
AB  - Staphylococcus aureus is one of the most common causes of hospital-acquired
      infections. At the same time, 25% of healthy persons are symptom-free S. aureus
      carriers, and they have an increased risk of developing nosocomial S. aureus
      septicemia. Paradoxically, their prognosis is much better than that of
      noncarriers. We compared the antibody profiles for carriers and noncarriers
      toward S. aureus superantigens. In carriers, we found high titers of neutralizing
      antibodies specific for those superantigens that are expressed by their
      colonizing strain. The results show that carriage status confers strain-specific
      humoral immunity, which may contribute to protection during S. aureus septicemia.

PMID- 16586366
TI  - Mycobacterium africanum elicits an attenuated T cell response to early secreted
      antigenic target, 6 kDa, in patients with tuberculosis and their household
      contacts.
AB  - BACKGROUND: Mycobacterium africanum, a member of the M. tuberculosis complex that
      is infrequently found outside of western Africa, is the cause of up to half of
      the tuberculosis cases there. METHODS: We genotyped mycobacterial isolates
      obtained from a study of patients with tuberculosis and their household contacts
      and compared T cell responses and tuberculin skin test results by infecting
      genotype. RESULTS: The T cell response to early secreted antigenic target, 6 kDa
      (ESAT-6), was attenuated in patients with tuberculosis (odds ratio [OR], 0.41
      [95% confidence interval {CI}, 0.19-0.89]; P = .024) and household contacts (OR,
      0.56 [95% CI, 0.38-0.83]; P = .004) infected with M. africanum, compared with the
      response in those infected with M. tuberculosis. In these same groups, responses
      to culture filtrate protein, 10 kDa (CFP-10), were nonsignificantly attenuated (P
      = .22 and P = .16, respectively), as were tuberculin skin test results (P = .30
      and P = .46, respectively). Sequencing of region of difference 1 of M. africanum
      revealed that Rv3879c is a pseudogene in M. africanum; however, this finding does
      not provide an obvious mechanism for the attenuated ESAT-6 response. CONCLUSIONS:
      This is the first evidence, to our knowledge, that strain differences affect
      interferon- gamma -based T cell responses. Our findings highlight the need to
      test new diagnostic candidates against different strains of mycobacteria.
      Integrating additional immunologic and genomic comparisons of M. tuberculosis and
      M. africanum into further studies may provide fundamental insights into the
      interactions between humans and mycobacteria.

PMID- 16586368
TI  - Incremental increase in fitness cost with increased beta -lactam resistance in
      pneumococci evaluated by competition in an infant rat nasal colonization model.
AB  - BACKGROUND: We evaluated the impact of resistant penicillin-binding protein (PBP)
      allele acquisition on the ability of penicillin-resistant (PEN-R) pneumococcal
      strains to compete with penicillin-susceptible (PEN-S) ancestors for upper
      respiratory-tract (URT) colonization. METHODS: PEN-S serotype 2, 6B, and 9V
      strains were transformed into derivatives expressing an increasing number of PEN
      R PBP forms (2X, 2X-1A, and 2X-1A-2B for serotype 2 and 2X, 2X-2B, and 2X-2B-1A
      for 6B and 9V). Infant rats were inoculated intranasally with a mix of a PEN-R
      and PEN-S strains. For consecutive days, samples were collected for assessment of
      the ratio of PEN-S to PEN-R cells colonizing the URT. The selective index (SI),
      defined as the change in the natural logarithm of the ratio of PEN-S to PEN-R
      strains from the inoculum to the nasal-wash samples, quantified differences in
      fitness. RESULTS: SIs significantly > 0 (indicating a cost of resistant allele
      acquisition) were observed 4-5 days after colonization in all but serotype 6B
      pbp2x transfomants. Additional replacements with low-affinity forms of pbp2b and
      pbp1a genes reduced further ability to compete in all strains. CONCLUSIONS: The
      cost of penicillin-resistance acquisition for the Streptococcus pneumoniae strain
      competing with its susceptible ancestor to colonize the URT increases with the
      number of resistant pbp alleles acquired.

PMID- 16586367
TI  - Mycobacterium tuberculosis invasion and traversal across an in vitro human blood
      brain barrier as a pathogenic mechanism for central nervous system tuberculosis.
AB  - BACKGROUND: Central nervous system (CNS) tuberculosis is a serious, often fatal
      disease that disproportionately affects young children. It is thought to develop
      when Mycobacterium tuberculosis breaches the blood-brain barrier (BBB), which is
      composed of tightly apposed brain microvascular endothelial cells. However, the
      mechanism(s) involved in this process are poorly understood. METHODS: To better
      understand these processes, we developed an in vitro model of M. tuberculosis BBB
      infection using primary human brain microvascular endothelial cells. RESULTS: M.
      tuberculosis was found to both invade and traverse the model BBB significantly
      more than did M. smegmatis (a nonpathogenic mycobacterium). Invasion by M.
      tuberculosis across the BBB required host-cell actin cytoskeletal rearrangements.
      By microarray expression profiling, we found 33 M. tuberculosis genes to be
      highly up-regulated during the early stages of invasion of the BBB by M.
      tuberculosis; 18 of them belong to a previously described in vivo-expressed
      genomic island (Rv0960-Rv1001). Defined M. tuberculosis isogenic transposon
      mutants for the up-regulated genes Rv0980c, Rv0987, Rv0989c, and Rv1801 were
      found to be deficient in their ability to invade the BBB model. CONCLUSIONS: We
      developed an in vitro model of M. tuberculosis BBB infection and identified M.
      tuberculosis genes that may be involved in CNS invasion.

PMID- 16586369
TI  - Progressive increase in point mutations associated with chloroquine resistance in
      Plasmodium falciparum isolates from India.
AB  - BACKGROUND: Effective malaria control programs require continuous monitoring of
      drug pressure in the field, using molecular markers. METHODS: We used sequence
      analysis to investigate the pfcrt and pfmdr1 mutations in Indian Plasmodium
      falciparum isolates. To evaluate the chloroquine drug pressure in the field,
      isolates were collected from 5 different areas at 2 time points, with an interval
      of 2 years. RESULTS: In 265 P. falciparum isolates, pfcrt mutations were observed
      at codons 72, 74, 75, 76, and 220, resulting in 8 different genotypes: SMNTS
      (61.89%), CIETS (12.08%), CMNKS (0.38%), CMNTA (2.64%), CMNTS (4.91%), SMNTA
      (0.38%), CIDTS (2.26%), and wild-type CMNKA (15.47%). During the 2-year period,
      there was a significant decrease in the number of isolates with the SMNTS
      genotype and an increase in the number of isolates with the highly chloroquine
      resistant pfcrt genotype CIETS (P < .05). The N86Y mutation was less prevalent
      (30.13%) than the Y184F mutation (99.16%) in the pfmdr1 gene in 239 isolates, but
      the number of isolates with the N86Y mutation increased significantly during the
      2-year period (P < .05). The number of isolates with higher total numbers of
      pfcrt and pfmdr1 2-loci mutations, therefore, increased significantly during this
      period. There was a regional bias in the mutation rate of these genes, because
      isolates from areas where chloroquine resistance was high had higher numbers of 2
      loci mutations, and areas where chloroquine resistance was low had isolates with
      lower numbers of 2-loci mutations. CONCLUSION: There was a temporal increase in
      the number of pfcrt and pfmdr1 2-loci mutations, and this led to the higher level
      of chloroquine resistance. This is a cause for concern for the antimalarial drug
      policy in India.

PMID- 16586370
TI  - CD4+CD25+ T cells in skin lesions of patients with cutaneous leishmaniasis
      exhibit phenotypic and functional characteristics of natural regulatory T cells.
AB  - Endogenous regulatory T (Treg) cells are involved in the control of infections,
      including Leishmania infection in mice. Leishmania viannia braziliensis is the
      main etiologic agent of cutaneous leishmaniasis (CL) in Brazil, and it is also
      responsible for the more severe mucocutaneous form. Here, we investigated the
      possible involvement of Treg cells in the control of the immune response in human
      skin lesions caused by L. viannia braziliensis infection. We show that functional
      Treg cells can be found in skin lesions of patients with CL. These cells express
      phenotypic markers of Treg cells--such as CD25, cytotoxic T lymphocyte-associated
      antigen 4, Foxp3, and glucocorticoid-induced tumor necrosis factor receptor--and
      are able to produce large amounts of interleukin-10 and transforming growth
      factor- beta . Furthermore, CD4+CD25+ T cells derived from the skin lesions of 4
      of 6 patients with CL significantly suppressed in vitro the phytohemagglutinin
      induced proliferative T cell responses of allogeneic peripheral-blood mononuclear
      cells (PBMCs) from healthy control subjects at a ratio of 1 Treg cell to 10
      allogeneic PBMCs. These findings suggest that functional Treg cells accumulate at
      sites of Leishmania infection in humans and possibly contribute to the local
      control of effector T cell functions.

PMID- 16586371
TI  - Both CD4+ and CD8+ T cells can mediate vaccine-induced protection against
      Coccidioides immitis infection in mice.
AB  - To determine which lymphocytes are required for vaccine-induced immunity to
      coccidioidomycosis, we used a temperature-sensitive mutant of Coccidioides
      immitis to immunize mice lacking subsets of lymphocytes or specific cytokines and
      infected the mice 4 weeks later with virulent C. immitis. After 2 weeks, we
      determined the number of fungi in their lungs and spleens. Vaccine-induced
      immunity required alpha beta T lymphocytes. beta -2 microglobulin knockout (KO)
      mice were protected by immunization, and we transferred protection using CD4+ T
      cells from immunized mice. However, vaccination also protected CD4+ KO mice,
      which suggests that CD8+ T cells played a role in vaccine-induced immunity, even
      though they were not required. We adaptively transferred protection using spleen
      cells from immunized CD4+ KO mice to nonimmune B6 mice, but CD8+ -depleted spleen
      cells did not protect against infection. Recipients of spleen cells from
      immunized CD4+ KO mice had 6 times more tumor necrosis factor (TNF)- alpha mRNA
      in their lungs than did mice that received nonimmune spleen cells, and TNF
      receptor-1 KO mice were not fully protected by immunization. These results show
      that both CD4+ and CD8+ T cells can protect against coccidioidomycosis and that
      TNF- alpha is a necessary component of the acquired immune response.

PMID- 16586372
TI  - Polymorphisms in Pneumocystis jirovecii strains in Spanish children with cystic
      fibrosis.

PMID- 16586373
TI  - Legionella bacteria in aerosols: sampling and analytical approaches used during
      the legionnaires disease outbreak in Pas-de-Calais.

PMID- 16586374
TI  - Viremia and clinical manifestations in children with rotavirus infection.

PMID- 16586375
TI  - Issues in Chlamydia trachomatis testing by nucleic acid amplification test.

PMID- 16586376
TI  - The decline in clinical sequelae of genital Chlamydia trachomatis infection
      supports current control strategies.

PMID- 16586378
TI  - Family outbreaks of invasive community-associated methicillin-resistant
      Staphylococcus aureus infection.
AB  - Outbreaks of invasive methicillin-resistant Staphylococcus aureus infection
      within families are unusual. We investigated 2 family clusters of invasive
      methicillin-resistant Staphylococcus aureus infection, including 1 in which a
      young mother died of fulminant pneumonia. Although surveillance via culture of
      family contacts of patients with invasive methicillin-resistant Staphylococcus
      aureus infection is not currently recommended, such clusters should stimulate
      reevaluation of preventive measures.

PMID- 16586379
TI  - The Antimicrobial Treatment Strategies (MIKSTRA) program: a 5-year follow-up of
      infection-specific antibiotic use in primary health care and the effect of
      implementation of treatment guidelines.
AB  - BACKGROUND: A national 5-year follow-up study of infection-specific antibiotic
      use in primary care was conducted to see if prescribing practices change after
      implementing new treatment guidelines. METHODS: The data were collected during 1
      week of November each year from 1998 to 2002 from 30 health care centers that
      covered a total population of 819,777 persons and in 2002 from 20 control health
      care centers that covered a population of 545,098 persons. National guidelines
      for 6 major infections (otitis media, sinusitis, throat infection, acute
      bronchitis, urinary tract infection, and bacterial skin infection) were published
      in 1999-2000. Multifaceted interventions were performed by local trainers
      teaching his or her coworkers, supported by feedback and patient and public
      information. RESULTS: The 6 infections targeted for intervention, together with
      unspecified upper respiratory tract infection constituted 80%-85% of all
      infections. The proportion of patients who received prescriptions for antibiotics
      did not change significantly. However, use of first-line antibiotics increased
      for all infections, and the change was significant for sinusitis (P<.001), acute
      bronchitis (P=.015), and urinary tract infections (P=.009). Also, the percentage
      of antibiotic treatments prescribed for the recommended duration increased
      significantly. Correct prescribing for respiratory tract infections improved by
      6.4 percentage units (P<.001). However, there was no statistically significant
      difference in performance between study and control health care centers at follow
      up. CONCLUSIONS: Moderate qualitative improvements in antibiotic use were
      observed after multifaceted intervention, but prescribing for unjustified
      indications, mainly acute bronchitis, did not decrease. Obtained infection
      specific information on management of patients with infections in primary health
      care is an important basis for planning targeted interventions in the future.

PMID- 16586380
TI  - Modifying antibiotic prescribing in primary care.

PMID- 16586381
TI  - West Nile virus disease: a descriptive study of 228 patients hospitalized in a 4
      county region of Colorado in 2003.
AB  - BACKGROUND: Risk factors for complications of West Nile virus disease and
      prognosis in hospitalized patients are incompletely understood. METHODS:
      Demographic characteristics and data regarding potential risk factors,
      hospitalization, and dispositions were abstracted from medical records for
      residents of 4 Colorado counties who were hospitalized in 2003 with West Nile
      virus disease. Univariate and multivariate analyses were used to identify factors
      associated with West Nile encephalitis (WNE), limb weakness, or death by
      comparing factors among persons with the outcome of interest with factors among
      those without the outcome of interest. RESULTS: Medical records of 221 patients
      were reviewed; 103 had West Nile meningitis, 65 had WNE, and 53 had West Nile
      fever. Respiratory failure, limb weakness, and cardiac arrhythmia occurred in all
      groups, with significantly more cases of each in the WNE group. Age, alcohol
      abuse, and diabetes were associated with WNE. Age and WNE were associated with
      limb weakness. The mortality rate in the WNE group was 18%; age,
      immunosuppression, requirement of mechanical ventilation, and history of stroke
      were associated with death. Only 21% of patients with WNE who survived returned
      to a prehospitalization level of function. The estimated incidence of West Nile
      fever cases that required hospitalization was 6.0 cases per 100,000 persons; West
      Nile fever was associated with arrhythmia, limb weakness, and respiratory
      failure. CONCLUSIONS: Persons with diabetes and a reported history of alcohol
      abuse and older persons appear to be at increased risk of developing WNE.
      Patients with WNE who have a history of stroke, who require mechanical
      ventilation, or who are immunosuppressed appear to be more likely to die.
      Respiratory failure, limb weakness, and arrhythmia occurred in all 3 categories,
      but there were significantly more cases of all in the WNE group.

PMID- 16586382
TI  - Dengue-related deaths in Puerto Rico, 1992-1996: diagnosis and clinical alarm
      signals.
AB  - BACKGROUND: Dengue, although endemic in Puerto Rico, is often not mentioned in
      the death certificates of decedents with laboratory results positive for dengue.
      Because confirmatory results are usually not available during hospitalization, we
      examined the utility of 2 instruments for diagnosis on the basis of clinical
      findings: the definition of dengue hemorrhagic fever (DHF) and the publicized
      (but unevaluated) clinical alarm signals for impending dengue shock. METHODS: We
      studied data from all patients with laboratory test results positive for dengue
      who died (23 patients) and from the 8 patients whose death certificates listed
      dengue as a cause of death but whose laboratory test results were negative for
      dengue in Puerto Rico from 1992 through 1996. We examined hospital records to
      determine whether the clinical criteria for DHF were fulfilled and evaluated the
      incidence and timing of clinical alarm signals (intense, sustained abdominal
      pain; persistent vomiting; sudden change from fever to hypothermia; and marked
      restlessness or lethargy) and the hematocrit/hemoglobin ratio as an indicator of
      hemoconcentration. RESULTS: A similar proportion of patients with laboratory test
      results positive for dengue (18 [78%] of 23) and negative for dengue (6 [75%] of
      8) fulfilled the criteria for DHF. Clinical alarm signals were found only among
      patients with laboratory test results positive for dengue and were usually noted
      on the day that the patient's condition deteriorated. The hematocrit/hemoglobin
      ratio identified 1 (6%) of 16 patients with dengue who had significant
      hemoconcentration. Important comorbidities were present in 16 (70%) of the
      patients with laboratory test results positive for dengue and in 4 (50%) of the
      patients with dengue-related deaths with laboratory test results negative for
      dengue. CONCLUSIONS: Dengue-related deaths in Puerto Rico often occur in patients
      with comorbidities. Among such patients, the DHF definition and the
      hematocrit/hemoglobin ratio were not useful in identifying patients with
      laboratory test results positive for dengue. In contrast, the clinical alarm
      signals for shock supported the dengue diagnosis and should alert clinicians to
      the severity of the disease.

PMID- 16586383
TI  - Salmonella enterica serovar Paratyphi A and S. enterica serovar Typhi cause
      indistinguishable clinical syndromes in Kathmandu, Nepal.
AB  - BACKGROUND: Enteric fever is a major global problem. Emergence of antibacterial
      resistance threatens to render current treatments ineffective. There is little
      research or public health effort directed toward Salmonella enterica serovar
      Paratyphi A, because it is assumed to cause less severe enteric fever than does
      S. enterica serovar Typhi. There are few data on which to base this assumption,
      little is known of the serovar's antibacterial susceptibilities, and there is no
      readily available tolerable vaccination. METHODS: A prospective study was
      conducted of 609 consecutive cases of enteric fever (confirmed by blood culture)
      to compare the clinical phenotypes and antibacterial susceptibilities in S. Typhi
      and S. Paratyphi A infections. Variables independently associated with either
      infection were identified to develop a diagnostic rule to distinguish the
      infections. All isolates were tested for susceptibility to antibacterials.
      RESULTS: Six hundred nine patients (409 with S. Typhi infection and 200 with S.
      Paratyphi A infection) presented during the study period. The infections were
      clinically indistinguishable and had equal severity. Nalidixic acid resistance,
      which predicts a poor response to fluoroquinolone treatment, was extremely common
      (75.25% of S. Paratyphi A isolates and 50.5% of S. Typhi isolates; P < .001). S.
      Paratyphi A was more likely to be resistant to ofloxacin (3.6% vs. 0.5%; P =
      .007) or to have intermediate susceptibility to ofloxacin (28.7% vs. 1.8%; P <
      .001) or ciprofloxacin (39.4% vs. 8.2%; P < .001). MICs for S. Paratyphi A were
      higher than for S. Typhi (MIC of ciprofloxacin, 0.75 vs. 0.38 microg/mL [P <
      .001]; MIC of ofloxacin, 2.0 vs. 0.75 microg/mL [P < .001]). CONCLUSIONS: The
      importance of S. Paratyphi A has been underestimated. Infection is common, the
      agent causes disease as severe as that caused by S. Typhi and is highly likely to
      be drug resistant. Drug resistance and lack of effective vaccination suggest that
      S. Paratyphi A infection may become a major world health problem.

PMID- 16586384
TI  - Selective transmission of hepatitis C virus quasi species through a needlestick
      accident in acute resolving hepatitis.
AB  - BACKGROUND: Little is known about the transmission of variant hepatitis C virus
      (HCV) genome through needlestick injuries. METHODS: To demonstrate how HCV quasi
      species are transmitted and adapt to the new host in acute resolving infection,
      we analyzed the nucleotide and deduced amino acid sequences of the hypervariable
      region 1 (HVR-1) in the E2 domain of HCV in both the source of the virus
      ("donor") and the person who received the virus through a needlestick accident
      ("recipient"). In addition, we also performed phylogenetic analysis of HCV quasi
      species in these patients to document the viral transmission. RESULTS: We
      obtained a total of 33 clones at different time points by using polymerase chain
      reaction amplification and cloning and sequencing of HVR-1. A predominant HVR-1
      variant (in 4 of 10 isolates) in the donor was not present in the recipient 6 and
      14 weeks after the accident. In contrast, a minor variant (in 1 of 10 isolates)
      in the donor became the predominant strain in the recipient 6 weeks (in 10 of 12
      isolates) and 14 weeks (in 6 of 11 isolates) after the accident. Additional
      phylogenetic analysis showed high homology of nucleotide sequences between
      isolates obtained from the donor and isolates obtained from the recipient. In
      addition, the variants in the recipient's virus showed substantial genetic
      preservation in the course of acute resolving hepatitis. CONCLUSIONS: These data
      suggested that a minor HCV variant from a donor was transmitted to the recipient
      through a needlestick injury and that it prevailed as the dominant species. The
      preserved genetic homogeneity of the transmitted viral variants in patients with
      acute HCV infection may account for their clinical outcomes of resolving
      hepatitis.

PMID- 16586385
TI  - Detection of antibodies against free-living amoebae Balamuthia mandrillaris and
      Acanthamoeba species in a population of patients with encephalitis.
AB  - BACKGROUND: Balamuthia mandrillaris and Acanthamoeba species are 2 free-living
      amoebae responsible for granulomatous amoebic encephalitis in humans and animals.
      We have screened serum samples from hospitalized patients with encephalitis for
      antibodies against these 2 amoebae as a means of detecting a disease with few
      defining symptoms and a poor prognosis. METHODS: Indirect immunofluorescence
      antibody (IFA) staining of serum samples from patients with encephalitis was
      conducted over a period of 6 years to detect amoeba antibodies. More than 250
      serum samples from patients hospitalized with encephalitis were screened. Most of
      the samples were from patients in California and were screened as part of the
      California Encephalitis Project, with a small number of specimens from other
      states. RESULTS: During the course of the study, 7 cases of Balamuthia
      encephalitis were detected; all cases were detected in Hispanic individuals, and
      all cases were fatal. Examination of hematoxylin-eosin-stained and immunostained
      sections of brain tissue obtained at biopsy or autopsy for amoebae confirmed
      balamuthiasis in all serum samples with positive IFA results. One case of
      Acanthamoeba encephalitis was detected in an immunocompromised individual with a
      normal antibody titer by identification of amoebae in immunostained brain tissue
      obtained at autopsy. CONCLUSIONS: IFA can be successfully used in screening for
      balamuthiasis and acanthamoebiasis in patients whose clinical presentation,
      laboratory results, and neuroimaging findings are suggestive of amoebic
      encephalitis. Ideally, this can lead to an earlier definitive diagnosis and
      earlier start of antimicrobial therapy. Without IFA staining, the balamuthiasis
      cases in our study would have been diagnosed as neurocysticercosis, tumor,
      tuberculosis, or viral encephalitis or would have been undiagnosed.

PMID- 16586386
TI  - Use of real-time quantitative polymerase chain reaction to monitor the evolution
      of Brucella melitensis DNA load during therapy and post-therapy follow-up in
      patients with brucellosis.
AB  - BACKGROUND: We performed quantitative real-time polymerase chain reaction (Q-PCR)
      to monitor the evolution of Brucella melitensis DNA load from initial diagnosis
      through post-therapy follow-up in patients with brucellosis. METHODS: On the
      basis of real-time fluorometric quantification of PCR products, we used the ultra
      rapid LightCycler system (Roche Diagnostics). We collected 180 peripheral blood
      samples from 18 patients with brucellosis. Analysis of bacterial DNA loads was
      performed for 2 groups: 11 patients who did not experience relapse and 7 patients
      who experienced relapse in the follow-up phase. RESULTS: Q-PCR was 100% specific
      for B. melitensis and showed an analytical sensitivity of 15 fg. Sensitivity of Q
      PCR for both initial infections and relapses was 100%. There were no
      statistically significant differences between groups with respect to bacterial
      DNA load from initial diagnosis to the end of post-treatment follow-up (P > .05).
      Evolution of the bacterial DNA load throughout the treatment phase was similar
      among patients who relapsed and did not relapse. Despite positive response to
      treatment and a sharp decrease in bacterial DNA load after initiating therapy,
      the results of Q-PCR on finalizing treatment for 50% of the patients (7 from the
      relapse group and 2 from the nonrelapse group) were low-level positive. At the
      conclusion of follow-up, almost 40% of the patients (4 from the relapse group and
      3 from the nonrelapse group), most of them asymptomatic, still maintained low
      bacterial DNA loads. CONCLUSIONS: Using Q-PCR techniques, we consistently
      detected B. melitensis DNA in the blood samples of patients with brucellosis
      throughout treatment and follow-up, despite apparent recovery from infection.
      These findings may have diagnostic, pathogenic, and therapeutic implications.

PMID- 16586387
TI  - Prediction of bacteremia using TREAT, a computerized decision-support system.
AB  - BACKGROUND: Prediction of bloodstream infection at the time of sepsis onset
      allows one to make appropriate and economical management decisions. METHODS: The
      TREAT computerized decision-support system uses a causal probabilistic network,
      which is locally calibrated, to predict cases of bacteremia. We assessed the
      system's performance in 2 independent cohorts that included patients with
      suspected sepsis. Both studies were conducted in Israel, Italy, and Germany. Data
      were collected prospectively and were entered into the TREAT system at the time
      that blood samples were obtained for culture. Discriminative power was assessed
      using a receiver-operating characteristics curve. RESULTS: In the first cohort,
      790 patients were included. The area under the receiver-operating characteristics
      curve for prediction of bacteremia using the TREAT system was 0.68 (95%
      confidence interval [CI], 0.63-0.73). We used TREAT's prediction values to draw
      thresholds defining a low-, intermediate-, and high-risk groups for bacteremia,
      in which 3 (2.4%) of 123, 62 (12.8%) of 483, and 55 (29.9%) of 184 patients were
      bacteremic, respectively. In the second cohort, 1724 patients were included. The
      area under the receiver-operating characteristics curve was 0.70 (95% CI, 0.67
      0.73). The prevalence of bacteremia observed in the low-, intermediate-, and high
      risk groups defined by the first cohort were 1.3% (4 of 300 patients), 13.2% (150
      of 1139 patients), and 28.1% (80 of 285 patients), respectively. The low-risk
      groups in the 2 cohorts comprised 15%-17% of all patients. Performance was stable
      in the 3 sites. CONCLUSIONS: Using variables available at the time that blood
      cultures were performed, the TREAT system successfully stratified patients on the
      basis of the risk for bacteremia. The system's predictions were stable in 3
      locations. The TREAT system can define a low-risk group of inpatients with
      suspected sepsis for whom blood cultures may not be needed.

PMID- 16586389
TI  - Antifungal therapy: lessons learned over the past 27 years.
AB  - As principal investigator of the National Institute of Allergy and Infectious
      Diseases-sponsored Mycoses Study Group for the past 27 years, I have been
      fortunate to play a role in the many advances in the field of clinical mycology
      and antifungal therapy. For the Finland lecture, I will briefly discuss the
      development of the Mycoses Study Group, provide an overview of the currently
      available antifungal agents, and describe advances and lessons related to the
      treatment and management of cryptococcal meningitis (the most common form of
      fungal meningitis), 3 important endemic mycoses (namely, blastomycosis,
      histoplasmosis, and coccidioidomycosis), candidemia and invasive candidiasis (the
      most common forms of nosocomial fungal disease), and invasive aspergillosis (the
      most common form of invasive mould disease). My concluding remarks will address
      the increasing hurdles and challenges, as well as the rewards, facing
      investigators who focus on clinical trials.

PMID- 16586390
TI  - Food safety guidance for older adults.
AB  - Aging is associated with loss of the physical barriers and immune efficiency that
      typically control pathogens' access to and multiplication within the body, thus
      making infection more likely in elderly persons. Chronic diseases and other
      health factors, such as malnutrition and immobility, may increase susceptibility
      to and severity of infections, including foodborne illnesses, in elderly persons,
      as well as associated morbidity and mortality. Prevention is the best way to
      avoid foodborne illnesses, but older adults have long-established food
      preparation and handling practices, some of which may increase the likelihood of
      illness. Elderly persons rely on physicians as trusted sources of health
      information. Physicians and other health care professionals can help prevent and
      control foodborne diseases by educating their patients about the risks of
      foodborne illness, providing sound advice on safe food-handling and consumption
      practices, making rapid appropriate diagnoses, and reporting cases promptly to
      public health authorities.

PMID- 16586388
TI  - Rifaximin, a nonabsorbed oral antibiotic, prevents shigellosis after experimental
      challenge.
AB  - BACKGROUND: This double-blind, placebo-controlled study was conducted to assess
      the efficacy of the nonabsorbed oral antibiotic rifaximin to prevent shigellosis
      in volunteers challenged with Shigella flexneri. METHODS: Volunteers were
      randomized to receive either prophylactic rifaximin (200 mg 3 times daily for 3
      days; n = 15) or placebo (n = 10) on days 0, 1, and 2. On day 1, volunteers were
      challenged with approximately 1500 colony-forming units of S. flexneri 2a strain
      2457T given orally in sodium bicarbonate buffer. RESULTS: The incidence of
      diarrhea was 0 with rifaximin, compared with 60% with placebo (P = .001). The
      median time to onset of diarrhea was 78.5 h with placebo (P < .001). The
      incidence of dysentery was 0 for rifaximin and 10% for placebo (P = .4). The
      incidence of colonization with Shigella was 0 with rifaximin, compared with 50%
      with placebo (P < .005). A significant serum or mucosal immune response after
      challenge by at least 1 indicator (immunoglobulin A titer, immunoglobulin G
      titer, and immunoglobulin A antibody-secreting cell count) was 0 with rifaximin
      and 80% with placebo (P < .001). CONCLUSIONS: Rifaximin was effective and well
      tolerated, compared with placebo, in preventing shigellosis in this double-blind
      study of volunteers challenged with S. flexneri 2a.

PMID- 16586391
TI  - Psychotropic medications and HIV.
AB  - Patients with human immunodeficiency virus (HIV) infection and acquired immune
      deficiency syndrome have high rates of psychiatric illness. The effective
      management of these psychiatric conditions can improve a patient's quality of
      life and may improve antiretroviral adherence. Care providers for patients with
      HIV infection frequently encounter clinical situations in which psychotropic
      medications are needed or are being used. Those clinical situations require
      familiarity with the broad category of medications termed "psychotropic." That
      familiarity should include a basic understanding of indications, adverse effects,
      and drug interactions. In particular, it is very important to recognize the many
      potential interactions based on cytochrome P450 metabolism, which is common to
      many psychotropics, the protease inhibitors, and the nonnucleoside reverse
      transcriptase inhibitors. In a brief review of the use of psychotropic
      medications in patients with HIV infection, we discuss indications, adverse
      effects, and drug interactions for commonly used antidepressants, mood
      stabilizers, anxiolytics, antipsychotics, psychostimulants, and drugs of abuse.

PMID- 16586392
TI  - Use of sentinel laboratories by clinicians to evaluate potential bioterrorism and
      emerging infections.
AB  - With the persistent threat of emerging infectious diseases and bioterrorism, it
      has become increasingly important that clinicians be able to identify the
      diseases that might signal the occurrence of these unusual events. Essential to a
      thoughtful diagnostic approach is understanding when to initiate a public health
      investigation and how to appropriately use commonly performed microbiology
      procedures in the sentinel laboratory to evaluate potential pathogens. Although
      diagnostic test development is evolving rapidly, recognizing many of these
      pathogens continues to challenge the capabilities of most sentinel laboratories.
      Therefore, effective, ongoing communication and education among clinicians,
      infection control personnel, sentinel laboratorians, public health authorities,
      and Laboratory Response Network reference laboratorians is the key to
      preparedness.

PMID- 16586394
TI  - Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1)
      illness predict mortality among high-risk HIV-1-infected African women.
AB  - BACKGROUND: There is limited information on the natural history of human
      immunodeficiency virus type 1 (HIV-1) infection in Africa, especially from
      individuals with well-defined dates of infection. We used data from a prospective
      cohort study of female sex workers in Mombasa, Kenya, who were followed up
      monthly from before the date of HIV-1 infection. METHODS: Antiretroviral-naive
      women who had a well-defined date of HIV-1 infection were included in this
      analysis. The effects of set point plasma viral load (measured 4-24 months after
      infection), early CD4+ cell count, and symptoms of acute HIV-1 infection on
      mortality were assessed using Cox proportional hazards analysis. RESULTS: Among
      218 women, the median duration of follow-up after HIV-1 infection was 4.6 years.
      Forty women died, and at 8.7 years (the time of the last death), the cumulative
      survival rate was 51% by Kaplan-Meier analysis. Higher set point viral load,
      lower early CD4+ cell count, and more-symptomatic acute HIV-1 illness each
      predicted death. In multivariate analysis, set point viral load (hazard ratio
      [HR], 2.28 per 1 log10 copies/mL increase; P=.001) and acute HIV-1 illness (HR,
      1.14 per each additional symptom; P=.05) were independently associated with
      higher mortality. CONCLUSION: Among this group of African women, the survival
      rate was similar to that for HIV-1-infected individuals in industrialized nations
      before the introduction of combination antiretroviral therapy. Higher set point
      viral load and more-severe acute HIV-1 illness predicted faster progression to
      death. Early identification of individuals at risk for rapid disease progression
      may allow closer clinical monitoring, including timely initiation of
      antiretroviral treatment.

PMID- 16586395
TI  - Polymorphonuclear leukocytes mainly contribute to human herpesvirus-6 load in the
      peripheral blood of patients.

PMID- 16586393
TI  - Endothelial function in HIV-infected persons.
AB  - BACKGROUND: Several reports have suggested an increased risk of coronary disease
      in human immunodeficiency virus (HIV)-infected patients receiving protease
      inhibitors (PIs). Impaired endothelium-dependent vasodilation is a putative
      surrogate marker of coronary atherosclerotic disease. METHODS: The present study
      evaluated the effect of HIV infection and antiretroviral treatment on endothelial
      vasomotor function, by assessing brachial artery flow-mediated dilation (FMD). A
      total of 75 HIV-infected patients were compared with 223 control subjects who
      were presumed to be HIV uninfected. RESULTS: HIV-infected patients had
      significantly impaired FMD, compared with control subjects (mean +/- SD, 7.3% +/-
      4.4% vs. 11.1% +/- 6.3%; P < .0001). When adjustments were made for smoking
      status, sex, and body mass index, the difference between the 2 groups remained
      statistically significant (P < .01). In a cross-sectional analysis of the HIV
      infected patients, we found significant associations between FMD and current
      injection drug use, hazardous drinking, HIV load, and alpha-high-density
      lipoprotein triglyceride levels, but not PI therapy. In a multivariate analysis,
      only current injection drug use and a lower alpha-high-density lipoprotein
      triglyceride level were significantly associated with FMD. CONCLUSIONS: HIV
      infected patients have significant impairment of endothelial function, and this
      impairment is worse among those with elevated levels of HIV replication,
      particularly injection drug users.

PMID- 16586396
TI  - Methicillin resistance and its relation to prognosis in patients with ventilator
      associated pneumonia: still an unsolved issue.

PMID- 16586397
TI  - Queen of Punt.

PMID- 16586398
TI  - Ritonavir-boosted atazanavir may be efficacious in HIV-infected patients
      concurrently receiving omeprazole.

PMID- 16586399
TI  - Improvement of dyslipidemia during different HAART regimens: tenofovir- versus
      stavudine-containing antiretroviral combinations.

PMID- 16586400
TI  - Reply to Bodi et al.

PMID- 16586402
TI  - Anomalously low probabilities for rotational excitation in HD-surface scattering.

PMID- 16586403
TI  - Testing for genetic heterogeneity in the genome search meta-analysis method.
AB  - The Genome Search Meta-Analysis (GSMA) method is widely used to detect linkage by
      pooling results of previously published genome-wide linkage studies. The GSMA
      uses a non-parametric summed rank statistic in 30 cM bins of the genome.
      Zintzaras and Ioannidis ([2005] Genet. Epidemiol. 28:123-137) developed a method
      of testing for heterogeneity of evidence for linkage in the GSMA, with three
      heterogeneity statistics (Q, Ha, B). They implement two testing procedures,
      restricted versus unrestricted for the summed rank within the bin. We show here
      that the rank-unrestricted test provides a conservative test for high
      heterogeneity and liberal test for low heterogeneity in linked regions. The rank
      restricted test should therefore be used, despite the extensive simulations
      needed. In a simulation study, we show that the power to detect heterogeneity is
      low. For 20 studies of affected sib pairs, simulated assuming linkage in all
      studies to a gene with sibling relative risk of 1.3, the power to detect low
      heterogeneity using the Q statistic was 14%. With linkage present in 50% of the
      studies (to a gene with sibling relative risk of 1.4), the Q heterogeneity
      statistic had power of 29% to detect high heterogeneity. The power to detect
      linkage using the summed rank was high in both of these situations, at 98% and
      79%, respectively. Although testing for heterogeneity in the GSMA is of interest,
      the currently available method provides little additional information to that
      provided by the summed rank statistic.

PMID- 16586404
TI  - Hypersensitivity pneumonitis due to metal working fluids: Sporadic or under
      reported?
AB  - BACKGROUND: Occupational exposure to metal working fluids (MWF) is common with
      over 1.2 million workers in the United States involved in machine finishing,
      machine tooling, and other metalworking operations. MWF is a known cause of
      hypersensitivity pneumonitis (HP). Recent reports of outbreaks of
      hypersensitivity HP secondary to exposure to MWF are reported. DESIGN: Cases were
      identified through the Occupational Disease surveillance system in the State of
      Michigan and from referrals for evaluation to the Division of Occupational and
      Environmental Medicine at Michigan State University (MSU). Each patient underwent
      a clinical examination including an occupational history, lung function studies,
      radiographic imaging, and in some cases lung biopsies. Following the diagnosis of
      definite HP, an industrial hygiene investigation was carried out, which included
      a plant walk-through, and review of the "Injury and Illness" log. Air monitoring
      and microbial sampling results were reviewed. RESULTS: As part of Michigan's
      mandatory surveillance system for occupational illnesses, seven cases of
      suspected HP were identified in 2003-2004 from three facilities manufacturing
      automobile parts in Michigan. Each plant used semi-synthetic MWFs, and conducted
      a MWF management program including biocide additions. Two facilities had recently
      changed the MWF before the cases arose. Growth of mycobacteria was found in these
      two MWFs. Breathing zone samples for particulates of two employees in plant A
      (two cases) ranged from 0.48 to 0.56 mg/m3. In plant B (four cases), two
      employees' sampling results ranged from 0.10 to 0.14 mg/m3. No air sampling data
      were available from plant C. CONCLUSION: Hypersensitivity pneumonitis due to
      exposure to MWFs is under-recognized by health care providers, and current
      surveillance systems are inadequate to provide a true estimate of its occurrence.
      HP arose from environments with exposures well below the Occupational Safety and
      Health Administration (OSHA) permissible exposure limit (PEL) for MWF, and in one
      case from exposures well below the National Institute of Occupational Safety and
      Health (NIOSH) recommended exposure limit (REL). The sporadic nature of reports
      of HP in relationship to MWF probably represents a combination of workplace
      changes that cause the disease and inadequate recognition and reporting of the
      disease when it does occur. Physician awareness of HP secondary to MWF and an
      effective medical surveillance program are necessary to better understanding the
      epidemiology and prevention of this disease.

PMID- 16586405
TI  - Occupational endotoxin-exposure and possible health effects on humans.
AB  - BACKGROUND: Endotoxins are commonly found at workplaces where large amounts of
      bioaerosols are generated. In Germany, especially since the Ordinance on Safety
      and Health Protection related to work involving biological agents (Biostoff
      Verordnung) became effective (1999), threshold limit values are widely discussed.
      Up to the present, endotoxin values are measured with non-uniform methods and
      therefore values are of limited benefit for classification of exposure groups. In
      Germany there is no threshold limit value for endotoxin. METHODS: Relevant
      literature of the last 20 years was selected from Medline and discussed. RESULTS:
      In this review we focused on the impact of endotoxin exposure on human health
      with special respect to the measurements on workplace and methodological aspects
      of endotoxin determination. Methods for sampling and endotoxin determination have
      to be validated, optimized, and standardized first. CONCLUSION: The adverse
      health effects of endotoxins are known, standardization of measurements is a
      necessary goal and protection measures should be established immediately.

PMID- 16586406
TI  - A cohort mortality study of leather tanners in Tuscany, Italy.
AB  - BACKGROUND: Work in leather tanning may involve exposure to a wide range of
      chemicals. Some of these are carcinogens or suspected carcinogens. Increased risk
      for a number of cancers have been reported, although there are considerable
      inconsistencies between studies. The present study investigates the mortality of
      leather tanners in Tuscany, Italy. METHODS: Tanneries were selected from the 1996
      Valdarno Inferiore Tanneries Census and were in operation since December 31,
      1970. Employees were followed until December 31, 1998 through company records,
      and the National and Regional Death Index. Demographic and work history data were
      abstracted from company payrolls. Regional mortality rates were used to calculate
      Standardized Mortality Ratio (SMR). Analyses were completed for the overall
      cohort (men and women) and for men who ever worked as of finisher, chrome
      tanners, and vegetable tanner (only men). RESULTS: The cohort consisted of 4,874
      workers (4,150 males and 724 females) employed in 92 tanneries active in 1996 and
      operating on December 31, 1970. Ascertainment of vital status and cause of death
      were completed for all individuals by the end of follow-up, December 31, 1998.
      Males showed increases for cancer of the endocrine glands (SMR 5.67, 4 observed
      (obs), 90% Confidence Intervals (CI) 195-1,308), blood diseases (SMR 3.29, 4 obs,
      90% CI 112-753), mental disorders (SMR 1.95, 6 obs, 90% CI 85-385), violence and
      accidents (SMR 1.30, 54 obs, 90% CI 102-163). Mortality from myeloid leukemia was
      increased in males (SMR 2.08, 5 obs, 90% CI 82-437) and in females (SMR 5.99, 2
      obs, 90% CI 106-1,887). One death from nasal cancer was observed versus 0.2
      expected. Mortality from lung cancer was increased among finishers (SMR 1.45, 19
      obs, 90% CI 95-212), an increase was observed also for bladder cancer (SMR 1.25,
      2 obs, 90% CI 22-393) and pancreatic cancer (SMR 1.20, 2 obs, 90% CI 21-379).
      CONCLUSIONS: The study confirms previous observations among tanners of increased
      mortality from lung, bladder, and pancreatic cancer. Noteworthy are the increased
      mortality from myeloid leukemia together with the new findings of an increased
      mortality from endocrine glands tumors, blood diseases, and psychiatric disorders
      which should be considered with caution because of the small number of cases and
      the novelty of the observation.

PMID- 16586407
TI  - How many work-related injuries requiring hospitalization in British Columbia are
      claimed for workers' compensation?
AB  - BACKGROUND: Workplace compensation claims datasets represent an important source
      of information on work-related injuries. This study investigated the concordance
      between hospital discharge records and workers' compensation records for work
      related serious injuries among a cohort of sawmill workers in British Columbia
      (BC), Canada. It also examined the extent to which workers' compensation
      capturing patterns varied by cause, severity of injuries, and demographic
      characteristics of workers. METHODS: Work-related injuries were identified in
      hospitalization records between April 1989 and December 1998, and were matched by
      dates and description of injury to compensation records. RESULTS: The agreement
      between the hospital records and compensation records was good (kappa = 0.84, P <
      0.01). A lower claim reporting rate for work-related hospitalization was observed
      for older and non-white workers. More serious injuries defined by longer length
      of stay and emergency admissions were more likely to be reported. Falls, struck
      against, and overexertion injuries had lower reporting rates; whereas, machinery
      related, cutting/piercing, and caught in/between injuries had higher reporting
      rates. CONCLUSIONS: When compared with hospital discharge records, the
      compensation agency underreported incidents of serious work-related injuries by
      10-15% among the sawmill workers.

PMID- 16586408
TI  - Parental exposure to lead and small for gestational age births.
AB  - BACKGROUND: Previous studies about the effect of lead exposure on adverse birth
      outcomes are still inconsistent and few studies estimate the relationship between
      parental lead exposure and small for gestational age (SGA) infants. An
      occupational cohort study to assess whether parental lead exposure would be
      related to decreased birth weight and shortened gestational ages of their
      offspring was conducted. Whether higher lead exposure doses would increase risks
      of low birth weight (LBW), preterm delivery, and SGA births was also
      investigated. METHODS: A Program to Reduce Exposure by Surveillance System-Blood
      Lead Levels (Press-BLLS) was established in Taiwan in July 1993. The names of
      workers exposed to lead was collected from this occupational blood-lead
      notification database. The birth outcomes of their offspring were determined by
      linking to the Taiwan birth registration database from 1993 to 1997. Only
      singleton births whose parental blood-lead concentrations were tested during
      pregnancy or prior to conception, or within a 1-year span before these two
      periods were included. RESULTS: Among 1,611 eligible births, 72 births were LBW,
      74 were preterm deliveries, and 135 were SGA. Maternal blood-lead concentrations
      (PbBs) equal to or more than 20 microg/dl had a higher risk of mothering a SGA
      child (risk ratio (RR) = 2.15; 95% confidence interval (CI), 1.15-3.83).
      CONCLUSIONS: Additional evidence of the effects of lead on adverse birth
      outcomes, especially for SGA births is reported. Maternal exposure to lead plays
      a more important role in the adverse effect on birth outcome than does paternal
      exposure.

PMID- 16586409
TI  - Risk of lung cancer from exposure to dusts and fibers in Leningrad Province,
      Russia.
AB  - BACKGROUND: Exposures to several dusts and fibers (DFs) have been established or
      suggested as etiologic factors for lung cancer. METHODS: To investigate lung
      cancer risk in relation to exposure to DFs, we identified 540 pathologically
      diagnosed lung cancer cases and 582 controls from the 1993-1998 autopsy records
      of the 88 hospitals of Leningrad Province, Russia. Lifetime job-specific exposure
      measurements were available for 15 organic, 15 man-made and 28 natural-inorganic
      agents. RESULTS: In male workers, increased risks were found for linen dust (OR =
      3.68, 95% CI 1.00-13.6, adjusted for age, smoking and residence), and unspecified
      DFs (OR = 1.44, 95% CI 1.07-1.94). Small non-significant excess risks were
      observed for quartz dust (OR = 1.27; 95% CI 0.83-1.93) and man-made vitreous
      fibers (MMVFs) (OR = 1.82, 95% CI 0.88-3.75). In female subjects, risks were non
      significantly associated with paper dust (OR = 1.77, 95% CI 0.74-4.20), and
      unspecified DFs (OR = 1.52, 95% CI 0.77-3.03). CONCLUSIONS: The study showed
      increased lung cancer risk for selected categories of DFs.

PMID- 16586410
TI  - A new quasi-interpenetrating network formed by poly(N-acryloyl-tris
      (hydroxymethyl)aminomethane and polyvinylpyrrolidone: separation matrix for
      double-stranded DNA and single-stranded DNA fragments by capillary
      electrophoresis with UV detection.
AB  - The preparation of a new separation matrix, quasi-interpenetrating networks
      (quasi-IPNs) formed by poly(N-acryloyl-Tris) (poly(tris-A)) and PVP, and its
      application for dsDNA and ssDNA fragments separation by CE with UV detection, are
      presented. This new quasi-IPN exhibited high sieving performance, good dynamic
      coating ability, and low viscosity. Single-base resolutions of dsDNA fragments
      (Rs = 0.92 for 123/124 bp) and ssDNA fragments (Rs = 0.65 for 123/124 base, Rs =
      0.48 for 309/310 base) were achieved by using the quasi-IPN of poly(tris-A)/PVP
      (2% + 2%) solution in a 31 cm effective length linear polyacrylamide (LPA)-coated
      column. Single-base separation of dsDNA fragments (Rs = 0.92 for 123/124 bp) was
      also obtained within 28 min in a 46.7 cm effective length bare column at higher
      160 V/cm electric field strength by using the same quasi-IPN solution. The RSD of
      the migration time measured for each DNA fragments was less than 1.5% in the bare
      column for nine continuous runs. The effects of temperature and electric field
      strength on the DNA separation were also investigated.

PMID- 16586411
TI  - A multiplex assay with 52 single nucleotide polymorphisms for human
      identification.
AB  - A total of 52 SNPs reported to be polymorphic in European, Asian and African
      populations were selected. Of these, 42 were from the distal regions of each
      autosome (except chromosome 19). Nearly all selected SNPs were located at least
      100 kb distant from known genes and commonly used STRs. We established a highly
      sensitive and reproducible SNP-typing method with amplification of all 52 DNA
      fragments in one PCR reaction followed by detection of the SNPs with two single
      base extension reactions analysed using CE. The amplicons ranged from 59 to 115
      bp in length. Complete SNP profiles were obtained from 500 pg DNA. The 52 loci
      were efficiently amplified from degraded samples where previously only partial
      STR profiles had been obtained. A total of 700 individuals from Denmark,
      Greenland, Somalia, Turkey, China, Germany, Taiwan, Thailand and Japan were
      typed, and the allele frequencies estimated. All 52 SNPs were polymorphic in the
      three major population groups. The mean match probability was at least 5.0 x 10(
      19) in the populations studied. Typical paternity indices ranged from 336 000 in
      Asians to 549 000 in Europeans. Details of the 52 SNP loci and population data
      generated in this work are freely available at http://www.snpforid.org.

PMID- 16586412
TI  - Optimization of protein extraction and solubilization for mature grape berry
      clusters.
AB  - Protein extraction from grape berries has been challenging, particularly in
      mature berries, which can have sugar concentrations as high as 26%. Grape skins
      and seeds contain large amounts of polyphenols, which can also interfere with
      efficient protein extraction. In plants, two extraction protocols, TCA/acetone
      based and phenol-based methods, have been mainly used to extract proteins from
      different organs or tissues on many species. However, few results have been
      reported for grape berry clusters. We wanted to determine which of these
      protocols was optimal for berry clusters in order to achieve both efficient
      protein extraction and high spot resolution on 2-D gels. Four protocols, derived
      from either TCA/acetone or phenol procedures, were tested on mature Cabernet
      Sauvignon whole berry clusters. The phenol-based protocols were superior to the
      TCA/acetone methods, showing larger protein yields and greater spot resolution on
      2-D gels. One method was clearly superior to the rest, a phenol-based extraction
      method combined with resuspension in the presence of both urea and thiourea as
      chaotropes. A total of 81 spots were excised and identified following MALDI
      TOF/TOF MS analyses. Their identification helped further characterize the
      specificity of each extraction procedure.

PMID- 16586413
TI  - A new approach for separating low-molecular-weight RNA molecules by staircase
      electrophoresis in non-sequencing gels.
AB  - Low-molecular-weight (LMW) RNA profiles, which include ribosomal and transfer RNA
      molecules with similar small sizes, are molecular signatures of microorganisms
      with a great potential in microbial identification. The greatest resolution of
      these profiles was achieved by staircase electrophoresis in sequencing gels.
      Nevertheless, this technique is difficult to use because it takes 7 h, the gels
      have large sizes and it is necessary to heat the system and to recycle the buffer
      to maintain the denaturing conditions and avoid smile effects. Most available
      sequencing slabs have no internal temperature control or homogenizing devices,
      which by contrast are present in some newly designed non-sequencing slabs.
      Nevertheless, these slabs present two important problems for separating LMW RNA
      molecules, the size of gels is only 20 cm (instead of 40 cm) and the maximum
      voltage that can be reached is only 840 V (instead 2400 V). Staircase
      electrophoresis follows a model in which the external polarization is
      incrementally modified with a constant time step value. In the present work, we
      experimentally confirmed that by reducing the time step and increasing the total
      number of steps a suitable resolution is achieved. Under these conditions,
      despite the smaller size of the gels and the lower values of the electric field,
      the intensity reaches higher values than in sequencing gels and the LMW RNA
      profiles are correctly separated in 5 h. The resolution of these profiles
      obtained in non-sequencing gels is similar to that obtained in sequencing ones
      facilitating the analysis of large populations of microorganisms in any
      laboratory.

PMID- 16586414
TI  - Electrophoretic mobility and molecular distribution studies of poly(amidoamine)
      dendrimers of defined charges.
AB  - Generation 5 ethylenediamine (EDA)-cored poly(amidoamine) (PAMAM) dendrimers (E5,
      E denotes the EDA core and 5 the generation number) with different degrees of
      acetylation and carboxylation were synthesized and used as a model system to
      investigate the effect of charge and the influence of dendrimer surface
      modifications on electrophoretic mobility (EM) and molecular distribution. The
      surface-modified dendrimers were characterized by size-exclusion chromatography,
      1H NMR, MALDI-TOF-MS, PAGE, and CE. The focus of our study was to determine how
      EM changes as a function of particle charge and molecular mass, and how the
      molecular distribution changes due to surface modifications. We demonstrate that
      partially modified dendrimers have much broader migration peaks than those of
      fully surface functionalized or unmodified E5 dendrimers due to variations in the
      substitution of individual dendrimer surfaces. EM decreased nonlinearly with
      increases in surface acetylation for both PAMAM acetamides and PAMAM succinamic
      acids, indicating a complex migration activity in CE separations that is not
      solely due to charge/mass ratio changes. These studies provide new insights into
      dendrimer properties under an electric field, as well as into the
      characterization of dendrimer-based materials being developed for medical
      applications.

PMID- 16586415
TI  - Supramolecular hybrids of [60]fullerene and single-wall carbon nanotubes.
AB  - Noncovalent interactions between purified HiPCO single-wall carbon nanotubes
      (SWNT) and a [60]fullerene-pyrene dyad, synthesized through a regioselective
      double-cyclopropanation process, produce stable suspensions in which the tubes
      are very well dispersed, as evidenced by microscopy characterization. Cyclic
      voltammetry experiments and photophysical characterization of the suspensions in
      organic solvents are all indicative of sizeable interactions of the pyrene moiety
      with the SWNT and, therefore, of the prevalence in solution of [60]fullerene
      pyreneSWNT hybrids.

PMID- 16586416
TI  - Crystallographic analysis of primary visual photochemistry.

PMID- 16586417
TI  - Allosterically coupled double induced fit for 1+1+1+1 self-assembly of a
      calix[6]trisamine, a calix[6]trisacid, and their guests.

PMID- 16586418
TI  - Formation of a methyleneimine moiety by reaction of a RuII-coordinated azide ion
      with methyl iodide.

PMID- 16586419
TI  - A PH-functionalized polyphosphazene: a macromolecule with a highly flexible
      backbone.

PMID- 16586420
TI  - Palladium-catalyzed coupling reactions for the stereoselective synthesis of tri-
      and tetrasubstituted alkenes.

PMID- 16586421
TI  - A near-infrared-fluorescent chemodosimeter for mercuric ion based on an expanded
      porphyrin.

PMID- 16586422
TI  - Adsorption of functionalized benzoic acids on MgSO4.H2O (100).
AB  - Using a combination of ab initio and semiempirical methods, adsorption problems
      on surfaces with large unit cells and low symmetry can still be studied. Here, a
      hybrid approach of density functional theory (DFT) and Hartree-Fock (HF) was
      used. As an example, we determined the geometry and the electronic properties of
      benzoic acid (BA), salicylic acid (SA) and para-salicylic acid (p-SA) adsorbed on
      MgSO(4).H(2)O (100), which are used as conditioner molecules for the
      electrostatic separation of minerals. Contrary to general expectations, these
      molecules are chemisorbed, with binding energies around 1.9 eV, forming bonds
      through the carboxylic O atom of the COOH groups in a nonplanar geometry,
      although the surface is a stoichiometric wide-band-gap insulator and the
      molecules stay intact. In contrast, a planar adsorption geometry turned out to be
      nonbonding. Bonding takes place by means of surface-molecule resonances due to
      the overlap of the valence band with molecular orbitals, assisted by a small
      charge-transfer molecule to the surface of around 0.15e. These combined
      interactions cause an intramolecular twist between the COOH group and the benzene
      ring.

PMID- 16586423
TI  - Photoexcitation and relaxation dynamics of catecholato-iron(III) spin-crossover
      complexes.
AB  - The photophysical properties of the ferric catecholate spin-crossover compounds
      [(TPA)Fe(R-Cat)]X (TPA=tris(2-pyridylmethyl)amine; X=PF(6) (-), BPh(4) (-); R
      Cat=catecholate dianion substituted by R=NO(2), Cl, or H) are investigated in the
      solid state. The catecholate-to-iron(III) charge-transfer bands are sensitive
      both to the spin state of the metal ion and the charge-transfer interactions
      associated with the different catecholate substituents. Vibronic progressions are
      identified in the near-infrared (NIR) absorption of the low-spin species.
      Evidence for a low-temperature photoexcitation process is provided. The
      relaxation dynamics between 10 and 100 K indicate a pure tunneling process below
      approximately 40 K, and a thermally activated region at higher temperatures. The
      relaxation rate constants in the tunneling regime at low temperature, k(HL)(T-
      >0), vary in the range from 0.58 to 8.84 s(-1). These values are in qualitative
      agreement with the inverse energy-gap law and with structural parameters. A
      comparison with ferrous spin-crossover complexes shows that the high-spin to low
      spin relaxation is generally faster for ferric complexes, owing to the smaller
      bond length changes for the latter. However, in the present case the
      corresponding rate constants are smaller than expected based on the single
      configurational coordinate model. This is attributed to the combined influence of
      the electronic configuration and the molecular geometry.

PMID- 16586424
TI  - Automatic identification of the left ventricle in cardiac cine-MR images: dual
      contrast cluster analysis and scout-geometry approaches.
AB  - PURPOSE: To evaluate the technical feasibility of two approaches--dual-contrast
      (DC) cluster analysis, and scout geometry (SG)--for automatic identification of
      the left ventricular (LV) cavity in short-axis (SA) cine-MR images. MATERIALS AND
      METHODS: The DC algorithm uses Fuzzy C-Means (FCM) cluster analysis of SA images
      from a black-blood double-inversion recovery turbo spin-echo (dual IR TSE)
      sequence, and bright-blood images from a steady-state free precession (SSFP)
      sequence. The SG algorithm employs geometric information from scout views (i.e.,
      vertical long-axis (VLA) and four-chamber (4CH) views). Both algorithms
      incorporate additional geometric continuity constraints along with LV region
      segmentation to identify the LV. The performance of both algorithms was compared
      on images of eight healthy volunteers, and the SG algorithm was further evaluated
      on images of 13 clinical patients. RESULTS: The DC algorithm identified the LV in
      89% (72/75 at end-diastole (ED) and 47/59 at end-systole (ES)) of the images from
      healthy volunteers, compared to 98% (74/75 at ED and 57/59 at ES) by the SG
      algorithm. Both methods are robust against interslice signal variations and
      misalignment. The DC method suffers from misregistration between the dual IR TSE
      and SSFP images near the apex at ES. The SG method identified the LV in 91%
      (112/122 at ED and 91/102 at ES) of the images from clinical patients.
      CONCLUSION: The SG method requires no additional scan, is robust and accurate,
      and performs better than the DC method for automatic identification of the LV.

PMID- 16586425
TI  - Synthesis of non-nucleosides: 7- and 1,3-substituents of new pyrrolo[2,3
      d]pyrimidin-4-ones on antiviral activity.
AB  - A series of non-nucleosides 9-47 were synthesized. Compounds 1-4 were reacted
      with formic acid (85%) to afford compounds 5-8. Then, the latter compounds were
      reacted with alkyl halides a-f (2-bromopropane, 2-bromobutane, benzyl bromide,
      benzyl chloromethyl ether, chloromethyl ethyl ether, phenacyl bromide) in the
      presence of NaH in dry DMF to give the desired compounds 9-47, which were
      evaluated for activity against herpes simplex virus type-II (HSV-II).

PMID- 16586426
TI  - Synthesis of some novel azo derivatives of 3,5-dimethyl-1-(2
      hydroxyethyl)pyrazole as potent analgesic agents.
AB  - A series of 1-(2-hydroxyethyl)-3,5-dimethylpyrazolylazo derivatives,
      incorporating thiosemicarbazide 2a-c, 1,3,4-thiadiazole 3a-c, and 1,2,4-triazole
      3-thione 4a-c were synthesized. The structure of these novel synthesized
      compounds 2a-c, 3a-c, and 4a-c was confirmed by spectral analysis. All these
      compounds were screened for their analgesic activity. Hot-plate and tail
      immersion tests were used for the determination of the analgesic activity.
      Morphine, an analgesic through both spinal and supraspinal pathways, was used as
      a standard test drug. All compounds were administered at a dose of 100 mg/kg i.p.
      Among the compounds, 2-(butylamino)-5-[((1-(2-hydroxyethyl)-3,5-dimethylpyrazole
      4-yl)azo)phenyl]-1,3,4-thiadiazole 3a and 4-[((1-(2-hydroxyethyl)-3,5
      dimethylpyrazole-4-yl)azo)phenyl]-4-(2-phenethyl)-2,4-dihydro-3H-1,2,4-triazole-3
      thione 4c showed analgesic effects in both tests. Especially 4c exerted strong
      analgesia starting at 30 min after injection.

PMID- 16586427
TI  - In vitro and in vivo antimalarial activity of derivatives of 1,10-phenanthroline
      framework.
AB  - A series of trisubstituted 1,10-phenanthrolines was prepared. These compounds
      exhibited mild to high biological activities in vitro both toward chloroquino
      resistant FcB1-Columbia and FcM29-Cameron strains and Nigerian chloroquino
      sensitive strain of Plasmodium falciparum. Cytotoxicity of the most active
      compounds was estimated showing that one compound (10) exhibited a selective
      activity against malaria parasite (selectivity indexes of 52 and 144).
      Antiplasmodial activity of this derivative was optimized by N-10 alkylation and
      the phenanthrolinium salt (15) submitted to an in vivo study using mice infected
      by P. vinckei petteri showing an ED50 of 7.86 mg/kg/day.

PMID- 16586428
TI  - Identification of differentially expressed proteins in colorectal cancer by
      proteomics: down-regulation of secretagogin.
AB  - To identify proteins with colorectal cancer-specific regulation, comparative 2-DE
      of individual-matched normal and neoplastic colorectal tissue specimens was
      performed. We found 15 protein spots with concordantly increased and 20 protein
      spots with concordantly decreased intensity in tumor tissue (expression
      regulation more than fivefold). Nine of these proteins were identified by MS/MS.
      Interestingly, one of the proteins, which exhibited a marked down-regulation in
      colorectal cancer tissues, was the recently identified endocrine cell-expressed
      protein secretagogin. The reduction of the secretagogin content in colorectal
      cancer tissues was confirmed by comparative immunoblotting (n = 17) and RT-PCR (n
      = 22) as well as by immunohistochemistry (n = 45) of individual-matched
      neoplastic and normal colorectal tissue specimens. Immunohistochemistry revealed
      absence of secretagogin-expressing cells in most of the colorectal cancer tissue
      specimens. However, some colorectal cancers were characterized by secretagogin
      expressing cells. In normal mucosa, positively stained cells exhibited a
      neuroendocrine cell-characteristic morphology and mucosal location. In colorectal
      cancer tissues, secretagogin-expressing cells were characterized by a malignant
      morphology. Our findings might represent the basis for the clinical application
      of secretagogin as a biomarker for a distinct subgroup of colorectal cancers.

PMID- 16586429
TI  - Changes in the rat heart proteome induced by exercise training: Increased
      abundance of heat shock protein hsp20.
AB  - Chronic exercise training elicits adaptations in the heart that improve pump
      function and confer cardioprotection. To identify molecular mechanisms by which
      exercise training stimulates this favorable phenotype, a proteomic approach was
      employed to detect rat cardiac proteins that were differentially expressed or
      modified after exercise training. Exercise-trained rats underwent six weeks of
      progressive treadmill training five days/week, 0% grade, using an interval
      training protocol. Sedentary control rats were age- and weight-matched to the
      exercise-trained rats. Hearts were harvested at various times (0-72 h) after the
      last bout of exercise and were used to generate 2-D electrophoretic proteome maps
      and immunoblots. Compared with hearts of sedentary rats, 26 protein spot
      intensities were significantly altered in hypertrophied hearts of exercise
      trained rats (p <0.05), and 12 spots appeared exclusively on gels from hearts of
      exercise-trained rats. Immunoblotting confirmed that chronic exercise training,
      but not a single bout of exercise, elicited a 2.5-fold increase in the abundance
      of one of the candidate proteins in the heart, a 20 kDa heat shock protein
      (hsp20) that persisted for at least 72 h of detraining. Thus, exercise training
      alters the cardiac proteome of the rat heart; the changes include a marked
      increase in the expression of hsp20.

PMID- 16586430
TI  - Mass spectrometric profiling of O-linked glycans released directly from
      glycoproteins in gels using in-gel reductive beta-elimination.
AB  - Glycosylation is a widespread PTM of proteins; the carbohydrate moieties provide
      various functional, immunological and structural aspects of both eukaryotic and
      prokaryotic glycoproteins. Traditional strategies used to analyse glycoprotein O
      glycans involve glycoprotein isolation, followed by glycan release using solution
      phase base-catalysed beta-elimination. However, in a proteomics context, mixtures
      of proteins and glycoproteins are routinely separated using SDS-PAGE. We have
      therefore developed a method to enable the profiling of O-linked glycans directly
      from glycoproteins on gels. This is achieved using in-gel reductive beta
      elimination followed by mass spectrometric analysis of the released glycans. Here
      we describe our demonstration of the feasibility of this approach, our
      development and optimisation of the procedure using bovine submaxillary gland
      glycoproteins as a standard, and then show its usefulness by applying the
      developed procedure to the analysis of the O-glycans from a glycoprotein band
      from a Coomassie-stained SDS-PAGE separation of a mixture of Mycobacterium avium
      capsular proteins and glycoproteins. The procedure has been shown to be
      applicable to both CBB- and silver-stained gels. The method offers a quick and
      easy way to identify the O-glycans from gel-separated glycoproteins within gel
      based proteomics workflows.

PMID- 16586431
TI  - Enrichment of low molecular weight fraction of serum for MS analysis of peptides
      associated with hepatocellular carcinoma.
AB  - A challenging aspect of biomarker discovery in serum is the interference of
      abundant proteins with identification of disease-related proteins and peptides.
      This study describes enrichment of serum by denaturing ultrafiltration, which
      enables an efficient profiling and identification of peptides up to 5 kDa. We
      consistently detect several hundred peptide-peaks in MALDI-TOF and SELDI-TOF
      spectra of enriched serum. The sample preparation is fast and reproducible with
      an average CV for all 276 peaks in the MALDI-TOF spectrum of 11%. Compared to
      unenriched serum, the number of peaks in enriched spectra is 4 times higher at an
      S/N ratio of 5 and 20 times higher at an S/N ratio of 10. To demonstrate utility
      of the methods, we compared 20 enriched sera of patients with hepatocellular
      carcinoma (HCC) and 20 age-matched controls using MALDI-TOF. The comparison of
      332 peaks at p < 0.001 identified 45 differentially abundant peaks that
      classified HCC with 90% accuracy in this small pilot study. Direct TOF/TOF
      sequencing of the most abundant peptide matches with high probability des-Ala
      fibrinopeptide A. This study shows that enrichment of the low molecular weight
      fraction of serum facilitates an efficient discovery of peptides that could serve
      as biomarkers for detection of HCC as well as other diseases.

PMID- 16586432
TI  - C-(2-chloroquinoline-3-yl)-N-phenyl nitrone: new synthetic antioxidant inhibits
      proliferation and induces apoptosis of breast carcinoma MCF-7 cells.
AB  - In this work, a new quinoline nitrone derivative, C-(2-chloroquinoline-3-yl)-N
      phenyl nitrone (CQPN) was successfully prepared and proved by spectral analysis.
      The antioxidant activity of CQPN against various radicals was investigated and
      its anti-cancer properties against different human tumor cell lines including the
      solid tumor cell lines hepatocarcinoma (Hep-G2) and breast carcinoma (MCF-7); the
      hematopoietic tumor cell line lymphoblastic leukemia (1301) was also explored.
      CQPN activities were compared to that of the known nitrone C-phenyl-N-tert-butyl
      nitrone (PBN). Our results showed that although PBN was the stronger antioxidant
      than CQPN, the latter was an effective scavenger of different non-physiological
      (1,1-diphenyl-2-picrylhyrazyl) and physiological (peroxyl and hydroxyl) radicals.
      Both of CQPN and PBN possess a significant inhibitory property against LPS
      stimulated NO production in macrophage. CQPN and PBN treatment resulted in a
      growth inhibition in Hep-G2 cells (IC50 31.42 microM and 18.6 microM,
      respectively). Unlike PBN, CQPN strongly inhibited the growth of MCF-7 cells
      (IC50 14.01 microM) in a dose-dependent manner. On contrary, CQPN and PBN
      exhibited a proliferative stimulatory activity of the immune cells including
      macrophages and lymphocytes. Exploring the cytotoxic effect of CQPN against MCF-7
      cells indicated that CQPN led to a major time-dependent disturbance in the cell
      cycle phases including progressive arrest in both S- and G2/M-phases. This
      disturbance was found to be associated with a kinetic induction of apoptosis. The
      novel nitrone derivative CQPN is a strong antioxidant, though less than PBN, and
      it may be an effective anti-proliferative compound against breast carcinoma.

PMID- 16586433
TI  - Identification of complement C3a as a candidate biomarker in human chronic
      hepatitis C and HCV-related hepatocellular carcinoma using a proteomics approach.
AB  - Although the significant risk factors for hepatocellular carcinoma (HCC) are well
      known from epidemiological studies, diagnosis of this disease at an early stage
      is difficult, and HCC remains one of the leading causes of cancer death
      worldwide. Thus, to identify any useful HCC-related biomarkers is still a need.
      We performed SELDI-TOF MS to identify differentially expressed proteins in HCC
      serum using weak cation exchange protein chips. Protein characterization was
      performed by 2-DE separation and nano flow LC-MS/MS. A total of 55 sera were
      collected from HCC patients and compared with those from 48 patients with chronic
      hepatitis and 9 healthy individuals. A candidate marker of about 8900 Da was
      detected as differentially expressed in patients with chronic hepatitis C and
      hepatitis C virus (HCV)-related HCC. We identified this differentially expressed
      protein as complement C3a. The expression of C3a in HCC sera was further
      validated by PS20 chip immunoassay and Western blotting. Complement C3a was found
      to be elevated in patients with chronic hepatitis C and HCV-related HCC. The
      combination of SELDI-TOF MS and 2-DE provides a solution to identify disease
      associated serum biomarkers.

PMID- 16586434
TI  - Systematical evaluation of the effects of sample collection procedures on low
      molecular-weight serum/plasma proteome profiling.
AB  - Blood is an ideal source for biomarker discovery. However, little has been done
      to address the effects of sampling, handling and storage procedures on
      serum/plasma proteomes. We used magnetic bead-based MALDI-TOF MS to
      systematically evaluate the influence of each procedure on low-molecular-weight
      serum/plasma proteome profiling on the basis of the whole spectra. We found that
      sampling procedures, including the selection of blood collection tubes and
      anticoagulants, variations in clotting time or time lag before centrifugation,
      and hemolysis, displayed significant effects on the proteomes. Moreover, serum
      and plasma were mutually incompatible for proteome comparison. By contrast,
      overnight fasting, handling procedures, including centrifugation speeds (1500 x g
      vs. 3000 x g) or time (15 min vs. 30 min), and storage conditions, such as at 4
      degrees C or 25 degrees C for up to 24 h or at -80 degrees C for up to 3 months,
      and repeated freeze/thaw of up to ten cycles, had relatively minor effects on the
      proteomes based upon our analysis of about 100 peaks. We concluded that low
      molecular-weight serum/plasma proteomes were diversely affected by sampling,
      handling and storage with most change from variations of sampling procedures. We
      therefore suggest the necessity of standardizing sampling procedure for proteome
      comparison and biomarker discovery.

PMID- 16586435
TI  - Identification of proteins released by follicular lymphoma-derived cells using a
      mass spectrometry-based approach.
AB  - The recent advent of mass spectrometry-based methodologies for the analysis of
      complex protein mixtures opens new opportunities for the discovery of biomarkers
      that may aid in the diagnostic work-up of cancer. Follicular lymphoma (FL) is the
      most common form of low-grade non-Hodgkin lymphoma in the Western Hemisphere.
      Identification of tumor markers that facilitate early disease detection would be
      a significant advance in the management of FL. We have employed a strategy that
      entailed propagation of a follicular-derived cell line in serum-free media,
      protein extraction, and reverse-phase liquid chromatography, with subsequent
      electrospray ionization and tandem mass spectrometry analysis for the
      identification of proteins that are released by FL. Using a two-peptide minimum
      per protein and standard criteria, 209 proteins (5.6% maximum predicted error
      rate) released from the FL cells were identified. The released proteins included
      several growth factors, cytokines, acute phase reactants and cellular components
      previously known to be present in FL cells. Importantly, a greater proportion of
      proteins previously unassociated with FL were identified with high statistical
      confidence. Our studies provide a list of proteins, which may be candidates for
      early screening, diagnosis and therapeutic monitoring of patients with a
      suspected or biopsy-confirmed diagnosis of FL.

PMID- 16586436
TI  - Proteomic analysis of injured spinal cord tissue proteins using 2-DE and MALDI
      TOF MS.
AB  - Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell
      survival and neurological integrity via complex and evolving molecular cascades
      whose interrelationships are not fully understood. Acute injury to the spinal
      cord undergoes sequential pathological change including hemorrhage, edema, axonal
      and neuronal necrosis, and demyelination. In the present study, we aimed to
      establish the proteomic profiles and characterization of the total protein
      expressed in traumatic injured spinal cord tissue by using 2-DE and matrix
      assisted laser desorption/ionization-TOF MS (MALDI-TOF MS). We performed
      proteomic analysis using 2-DE and MS to describe total proteins and differential
      proteins expression between normal and traumatic injured spinal cord tissues. The
      study discovered 947 total proteins and analyzed 219 and 270 proteins from normal
      and injured tissue, respectively. After 24 h of traumatic damage induction, the
      injured spinal cord tissue up-regulated over 39 proteins including neurofilament
      light chain, annexin 5, heat shock protein, tubulin beta, peripherin, glial
      fibrillary acidic protein delta, peroxiredoxin 2, and apolipoprotein A. Twenty
      one proteins showed reduction. The majority of the modulated proteins belonged to
      the 13 functional categories. Proteins that were identified with neural
      functional category in injured tissue were considered most likely to be involved
      in wound healing response coupled with neurogenesis and gliogenesis.

PMID- 16586437
TI  - Functional analysis of the nuclear proteome of human A549 alveolar epithelial
      cells by HPLC-high resolution 2-D gel electrophoresis.
AB  - The airway epithelial cell plays a central role in coordinating airway
      inflammatory responses, where significant changes in the proteome occur in
      response to infectious stimuli. To further understand the spectrum of proteins
      and the biological processes they control, we have initially determined the
      nuclear proteome of human type II-like alveolar epithelial cells (A549) using a
      sequential method of organellar enrichment followed by HPLC prefractionation
      prior to 2-DE-based protein identification using MALDI-TOF MS. This approach
      yielded 719 high-confidence identifications, 433 mapping to unique gene
      identifiers. Expert classification showed that these proteins controlled
      chromatin remodeling, protein refolding, cytoskeletal structure, membrane
      function, metabolic processes, mitochondrial function, RNA binding, protein
      synthesis, signaling, and transcription factor activities. The proteins were
      mapped to gene ontology classifications, where metabolism and catalytic activity
      functions were significantly enriched, representing 43 and 32% of the protein
      set, respectively. Pathways analysis indicated a protein network affecting tumor
      necrosis factor-nuclear factor-kappaB signaling pathway interacting with
      intermediate cytoskeletal filaments. Forty-five proteins of unknown function were
      subjected to domain analysis and inferred to have additional nuclear functions
      controlling purine nucleotide metabolism and protein-protein interactions. This
      database represents the most comprehensive data set of mammalian nuclear proteins
      and will serve as a foundation for further discovery.

PMID- 16586438
TI  - Poly(epsilon-caprolactone) biomaterial sterilized by E-beam irradiation.
AB  - The effects of ionizing radiation (electron beam) on poly(epsilon-caprolactone)
      (PCL) were studied by analyzing changes in viscosity-average and weight-average
      molecular weight and radius of gyration, and by performing sol-gel analysis and
      swelling tests. Samples were irradiated under various conditions: solid and
      molten PCL in the presence or absence of air. The overall efficiency of
      crosslinking is higher for samples irradiated in the molten state than in the
      solid state, and is reduced in the presence of oxygen. Based on three kinds of
      experiments (molecular weight dependence on the dose in the pre-gelation region,
      sol-gel analysis, and swelling study), radiation-chemical yields of
      intermolecular crosslinking and scission were determined and are discussed in
      terms of the mechanism of radiation-induced reactions in PCL. Properties of the
      gels formed by high-dose irradiation and mechanical properties of irradiated PCL
      were analyzed. Irradiation causes an increase in the compression modulus of PCL.
      This process occurs at the pre-gelation stage and continues in the gel-containing
      system. We have demonstrated, for the first time, that irradiation of solid PCL
      is accompanied by a pronounced post-effect, which manifests itself by changes in
      the average molecular weight. EPR data indicate that this effect, at least in
      part, is caused by the presence of long-lived radicals trapped in the crystalline
      regions. Irradiation with the sterilizing dose does not cause a statistically
      significant change in the biocompatibility of PCL after subsequent storage for 79
      d, as determined by preliminary osteoblast vitality tests.

PMID- 16586439
TI  - Timing and expression pattern of carbonic anhydrase II in pancreas.
AB  - In the search for genetic markers for assessing the role of duct cells in
      pancreas growth, we examined whether carbonic anhydrase II (CAII) has ductal cell
      specificity. We determined the distribution and timing of CAII expression in
      mouse pancreas from embryonic stage to adult. The pancreatic ducts only start
      expressing CAII at embryonic day (E) 18.5, with increases after birth. Around
      E15.5, glucagon-positive cells, but not insulin-positive cells, also express
      CAII, with further increases by adult. CAII expression was restricted to cells
      within ductal structures and glucagon-positive cells with no colocalization with
      any insulin-positive cells at any time. In the human pancreas, CAII expression is
      restricted to the ducts. Furthermore, the activity of a 1.6-kb fragment of the
      human promoter with Luciferase assays was moderately strong compared with the
      cytomegalovirus promoter in human pancreatic duct cell line (PANC-1). Thus, we
      believe that the CAII gene could serve as a useful pancreatic duct cell marker.

PMID- 16586440
TI  - Distant regulatory elements in a Sox10-beta GEO BAC transgene are required for
      expression of Sox10 in the enteric nervous system and other neural crest-derived
      tissues.
AB  - Sox10 is an essential transcription factor required for development of neural
      crest-derived melanocytes, peripheral glia, and enteric ganglia. Multiple
      transcriptional targets regulated by Sox10 have been identified; however, little
      is known regarding regulation of Sox10. High sequence conservation surrounding 5'
      exons 1 through 3 suggests these regions might contain functional regulatory
      elements. However, we observed that these Sox10 genomic sequences do not confer
      appropriate cell-specific transcription in vitro when linked to a heterologous
      reporter. To identify elements required for expression of Sox10 in vivo, we
      modified bacterial artificial chromosomes (BACs) to generate a Sox10betaGeoBAC
      transgene. Our approach leaves endogenous Sox10 loci unaltered, circumventing
      haploinsufficiency issues that arise from gene targeting. Sox10betaGeoBAC
      expression closely approximates Sox10 expression in vivo, resulting in expression
      in anterior dorsal neural tube at embryonic day (E) 8.5 and in cranial ganglia,
      otic vesicle, and developing dorsal root ganglia at E10.5. Characterization of
      Sox10betaGeoBAC expression confirms the presence of essential regulatory regions
      and additionally identifies previously unreported expression in thyroid
      parafollicular cells, thymus, salivary, adrenal, and lacrimal glands. Fortuitous
      deletions in independent Sox10betaGeoBAC lines result in loss of transgene
      expression in peripheral nervous system lineages and coincide with evolutionarily
      conserved regions. Our analysis indicates that Sox10 expression requires the
      presence of distant cis-acting regulatory elements. The Sox10betaGeoBAC transgene
      offers one avenue for specifically testing the role of individual conserved
      regions in regulation of Sox10 and makes possible analysis of Sox10+ derivatives
      in the context of normal neural crest development.

PMID- 16586441
TI  - Retinoids and spermatogenesis: lessons from mutant mice lacking the plasma
      retinol binding protein.
AB  - Using Rbp4-null mice as models, we have established for the first time the
      kinetics of the spermatogenetic alterations during vitamin A deficiency (VAD).
      Our data demonstrate that the VAD-induced testicular degeneration arises through
      the normal maturation of germ cells in a context of spermatogonia differentiation
      arrest. They indicate that retinoic acid (RA) appears dispensable for the
      transition of premeiotic to meiotic spermatocytes, meiosis, and spermiogenesis.
      They confirm that RA plays critical roles in controlling spermatogonia
      differentiation, spermatid adhesion to Sertoli cells, and spermiation, and
      suggest that the VAD-induced arrest of spermatogonia differentiation results from
      simultaneous blocks in RA-dependent events mediated by RA receptor gamma
      (RARgamma) in spermatogonia and by RARalpha in Sertoli cells. They also provide
      evidence that expression of major RA-metabolizing enzymes is increased in mouse
      Sertoli cells upon VAD and that vitamin A-deficient A spermatogonia differ from
      their RA-sufficient counterparts by the expression of the Stra8 gene.

PMID- 16586442
TI  - Morphoregulation of avian beaks: comparative mapping of growth zone activities
      and morphological evolution.
AB  - Avian beak diversity is a classic example of morphological evolution. Recently,
      we showed that localized cell proliferation mediated by bone morphogenetic
      protein 4 (BMP4) can explain the different shapes of chicken and duck beaks (Wu
      et al. [2004] Science 305:1465). Here, we compare further growth activities among
      chicken (conical and slightly curved), duck (straight and long), and cockatiel
      (highly curved) developing beak primordia. We found differential growth
      activities among different facial prominences and within one prominence. The duck
      has a wider frontal nasal mass (FNM), and more sustained fibroblast growth factor
      8 activity. The cockatiel has a thicker FNM that grows more vertically and a
      relatively reduced mandibular prominence. In each prominence the number, size,
      and position of localized growth zones can vary: it is positioned more rostrally
      in the duck and more posteriorly in the cockatiel FNM, correlating with beak
      curvature. BMP4 is enriched in these localized growth zones. When BMP activity is
      experimentally altered in all prominences, beak size was enlarged or reduced
      proportionally. When only specific prominences were altered, the prototypic
      conical shaped chicken beaks were converted into an array of beak shapes
      mimicking those in nature. These results suggest that the size of beaks can be
      modulated by the overall activity of the BMP pathway, which mediates the growth.
      The shape of the beaks can be fine-tuned by localized BMP activity, which
      mediates the range, level, and duration of locally enhanced growth. Implications
      of topobiology vs. molecular blueprint concepts in the Evo-Devo of avian beak
      forms are discussed.

PMID- 16586443
TI  - Microtubule polarity and axis formation in the Drosophila oocyte.
AB  - The body axes of the fruit fly are established in mid-oogenesis by the
      localization of three mRNA determinants, bicoid, oskar, and gurken, within the
      oocyte. General mechanisms of RNA localization and cell polarization, applicable
      to many cell types, have emerged from investigation of these determinants in
      Drosophila oogenesis. Localization of these RNAs is dependent on the germline
      microtubules, which reorganize to form a polarized array at mid-oogenesis in
      response to a signaling relay between the oocyte and the surrounding somatic
      follicle cells. Here we describe what is known about this microtubule
      reorganization and the signaling relay that triggers it. Recent studies have
      identified a number of ubiquitous RNA binding proteins essential for this
      process. So far, no targets for any of these proteins have been identified, and
      future work will be needed to illuminate how they function to reorganize
      microtubes and whether similar mechanisms also exist in other cell types.

PMID- 16586444
TI  - Overview of the European and North American studies on HPV testing in primary
      cervical cancer screening.
AB  - Several studies suggest that HPV testing is more sensitive than cytology in
      primary cervical screening. These studies had different designs and were reported
      in different ways. Individual patient data were collected for all European and
      North American studies in which cytology was routinely performed and HPV testing
      was included as an additional parallel test. More than 60,000 women were
      included. The sensitivity and specificity of HPV testing were compared with
      routine cytology, both overall and for ages <35, 35-49 and 50+. The age-specific
      prevalence of high risk HPV (hr-HPV) was also analysed. HPV testing was
      substantially more sensitive in detecting CIN2+ than cytology (96.1% vs. 53.0%)
      but less specific (90.7% vs. 96.3%). The sensitivity of HPV testing was similar
      in all studies carried out in different areas of Europe and North America,
      whereas the sensitivity of cytology was highly variable. HPV sensitivity was
      uniformly high at all ages, whereas the sensitivity of cytology was substantially
      better in women over the age of 50 than in younger women (79.3% vs. 59.6%). The
      specificity of both tests increased with age. Positivity rates for HPV testing in
      women without high-grade CIN were region dependent. These results support the use
      of HPV testing as the sole primary screening test, with cytology reserved for
      women who test HPV positive. Large demonstration projects are needed to fully
      evaluate this strategy.

PMID- 16586445
TI  - Evidence for the regulation of left-right asymmetry in Ciona intestinalis by ion
      flux.
AB  - Vertebrate embryos develop distinct left-right asymmetry under the control of a
      conserved pathway involving left-sided deployment of the nodal and Pit x 2 genes.
      The mechanism that initiates asymmetric expression of these genes is less clear,
      with cilia, ion flux, and signalling molecules all implicated. Vertebrates share
      the chordate phylum with urochordates such as the sea squirt Ciona intestinalis.
      We have explored the role of ion flux in regulating left-right asymmetry in
      Ciona, using an assay in which perturbation of left-sided Ci-Pitx expression
      provides a read-out for the disruption of asymmetry. Our data show that
      omeprazole, which specifically inhibits H(+)K(+)ATPase activity, disrupts
      asymmetry in Ciona. The vertebrate H(+)K(+)ATPase is composed of two subunits,
      alpha and beta. We identified one Ciona beta ortholog and two Ciona alpha
      orthologs of the vertebrate H(+)K(+)ATPase genes, and show that one of these is
      expressed in dorsal and ventral embryonic midline cells shortly before the
      activation of left-sided Ci-Pitx expression. Furthermore, we show that omeprazole
      exerts its effect on asymmetry at this point in development, and additionally
      implicate K(+) channels in the regulation of asymmetry in Ciona. These
      experiments demonstrate a role for ion flux in the regulation of asymmetry in
      Ciona, and show a conserved, ancestral role for the H(+)K(+)ATPase ion pump in
      this process.

PMID- 16586446
TI  - Stop-flow kinetics studies of the interaction of surfactant, sodium dodecyl
      sulfate, with acid-denatured cytochrome c.
AB  - Interactions of sodium dodecyl sulfate (SDS) at submicellar and micellar
      concentration, with the globular protein, horse heart cytochrome c, at low pH
      have been shown to stabilize two molten globule-like intermediates. These dynamic
      studies were performed using far-UV, near-UV, and Soret-band circular dichroism
      (CD) as well as fluorescence methods. Stopped-flow CD and fluorescence studies of
      acid-denatured cytochrome c refolding with SDS were performed at both submicellar
      and micellar concentrations. Distinctive refolding mechanisms (from analysis of
      both CD and fluorescence) were found under these two conditions, and an obvious
      refolding intermediate was evident in the fluorescence traces. In addition,
      stopped-flow CD in the Soret region showed multistep kinetics, suggesting that
      the spectral changes in this region are not only solvent effect related but also
      connected with the change of secondary structure. A possible folding mechanism is
      proposed to rationalize the kinetics results.

PMID- 16586447
TI  - Clomiphene and hypospadias on a detailed level: signal or chance?
AB  - BACKGROUND: Clomiphene, a drug used to induce ovulation, is chemically related to
      diethylstilbestrol (DES). DES is associated with vaginal cancer and infertility
      among daughters and with hypospadias among second-generation male offspring.
      Because clomiphene has a long half-life and metabolites have been found in feces
      up to 6 weeks after administration, fetal exposure is possible if the mother took
      this drug prior to becoming pregnant. METHODS: Case-control analyses were
      performed to investigate the association between clomiphene exposure and
      hypospadias. Cases were all male subjects registered in the European Concerted
      Action on Congenital Anomalies and Twins (EUROCAT) Northern Netherlands registry
      for congenital anomalies with nonsyndromal hypospadias. Controls were all male
      children born without hypospadias, including those with chromosomal and monogenic
      defects. Logistic regression analyses were performed to calculate odds ratios
      (ORs) and 95% confidence intervals (CIs). RESULTS: Of 392 cases, 7 (1.8%) were
      exposed to clomiphene compared with 64 of 4538 controls (1.4%). For penoscrotal
      hypospadias, we found that the OR was significantly increased (6.08; 95% CI, 1.40
      26.33); for the mild and moderate forms of hypospadias, the ORs were not
      increased. CONCLUSIONS: Because penoscrotal hypospadias is rare, the effect is
      diluted when all forms of hypospadias are studied as a group. Therefore, our
      study stresses the importance of studying birth defects on as detailed a level as
      possible. Other studies should be conducted to confirm our findings.

PMID- 16586448
TI  - Expression of folate pathway genes in the cartilage of Hoxd4 and Hoxc8 transgenic
      mice.
AB  - BACKGROUND: Hox transcription factors are well known for their role in skeletal
      patterning in vertebrates. They regulate gene expression during the development
      of cartilage, the precursor to mature bone. We previously reported that
      overexpression of the homeobox genes Hoxc8 and Hoxd4 results in severe cartilage
      defects, reduced proteoglycan content, accumulation of immature chondrocytes, and
      decreased maturation to hypertrophy. We have also shown that Hoxd4 transgenic
      mice whose diets were supplemented with folate had their skeletal development
      restored. Since folate is required for growth and differentiation of
      chondrocytes, we hypothesized that the beneficial effect of folate in Hoxd4
      transgenic mice might indicate a local deficiency in folate utilization, possibly
      caused by deregulation of genes encoding folate transport proteins or folate
      metabolic enzymes. METHODS: We assayed the prevalence of transcripts for 22
      folate transport proteins and metabolizing enzymes, here collectively referred to
      as folate pathway genes. Quantitative real-time PCR was performed on cDNA samples
      derived from RNA isolated from primary chondrocytes of individual rib cartilages
      from Hoxd4 and Hoxc8 transgenic mice, respectively. RESULTS: This study shows
      that the Hox transgenes produce overexpression of Hoxd4 and Hoxc8 in primary
      chondrocytes from perinatal transgenic mice. However, no differences were found
      in expression levels of the folate pathway genes in transgenic cells compared to
      littermate controls. CONCLUSIONS: Our results provide evidence that folate
      pathway genes are only indirect targets of Hox transgene overexpression in our
      transgenic animals. These expression studies provide a baseline for future
      studies into the role of folate metabolism in chondrocyte differentiation.

PMID- 16586449
TI  - Long-circulating liposomal contrast agents for magnetic resonance imaging.
AB  - Contrast-enhanced magnetic resonance imaging (CE-MRI) is a dynamic technique for
      imaging vasculature. However, the currently used gadolinium (Gd) chelates, such
      as Gd-DTPA, restrict the time window for image acquisition due to their rapid
      elimination from blood and their rapid diffusion into the extravascular space,
      which prevents their use in steady-state imaging, particularly for MR angiography
      (MRA). The goal of this study was to prepare long-circulating polyethylene glycol
      bearing ((PEG)ylated) liposomes encapsulating Gd chelate, and characterize and
      demonstrate their utility for MRA. The liposomes were prepared by hydrating a
      mixture of lipids with gadodiamide (Omniscan). The liposomes were sized down to
      around 100 nm by extruder and exhaustively dialysed to remove the unencapsulated
      gadodiamide. The Gd liposomes exhibited a significant sustained (>4 hr) contrast
      enhancement of the vasculature with improved spatial details in a rat model with
      little leakage relative to Gd-DTPA controls as shown by MRI. We suggest that such
      long-circulating liposomal formulations allow for high spatial resolution imaging
      without the confounding effects of clearance and extravascular diffusion of the
      agent complicating the data and image analysis.

PMID- 16586450
TI  - Interactive continuously moving table (iCMT) large field-of-view real-time MRI.
AB  - Continuously moving table (CMT) MRI is a new method that is capable of generating
      3D, seamless, large field-of-view (FOV) images by acquiring readouts along the
      patient superior-inferior axis as the subject is translated through the scanner.
      For applications that require artifact-free images, such as arterial-phase
      contrast-enhanced (CE) angiography of the legs, a major challenge is to match the
      MR data acquisition and patient table motion with the dynamics of blood flow in
      the region of interest (ROI). Instead of restricting the CMT to predetermined
      constant table speeds, we adopted a more general approach in which the table
      motion is decoupled from the phase-encoding order. In our approach the table
      moves adaptively and in response to operator-provided feedback obtained from
      viewing real-time preview (or fluoroscopic) images. This interactivity is
      accomplished by integrating high temporal-spatial resolution encoding of the
      table position with real-time hybrid-space filling and image reconstruction.
      Experimental results obtained using our prototype interactive CMT (iCMT) system
      on a peripheral vascular phantom and five healthy volunteers demonstrate the
      feasibility of this robust and rapid imaging method for acquiring 3D large-FOV
      continuous images with patient-specific adaptive table motion profiles.

PMID- 16586451
TI  - Fast CT-PRESS-based spiral chemical shift imaging at 3 Tesla.
AB  - A new sequence is presented that combines constant-time point-resolved
      spectroscopy (CT-PRESS) with fast spiral chemical shift imaging. It allows the
      acquisition of multivoxel spectra without line splitting with a minimum total
      measurement time of less than 5 min for a field of view of 24 cm and a nominal
      1.5x1.5-cm2 in-plane resolution. Measurements were performed with 17 CS encoding
      steps in t1 (Deltat1=12.8 ms) and an average echo time of 151 ms, which was
      determined by simulating the CT-PRESS experiment for the spin systems of
      glutamate (Glu) and myo-inositol (mI). Signals from N-acetyl-aspartate, total
      creatine, choline-containing compounds (Cho), Glu, and mI were detected in a
      healthy volunteer with no or only minor baseline distortions within 14 min on a 3
      T MR scanner.

PMID- 16586452
TI  - Quantification of vitamin C in the rat brain in vivo using short echo-time 1H
      MRS.
AB  - Both ultrashort echo-time STEAM and MEGA-PRESS-edited spectroscopy were used to
      validate noninvasive quantification of vitamin C (ascorbate) in the developing
      rat brain, where changes in ascorbate concentration have been reported. Despite
      strong overlap with resonances from glutamine, glutamate, glutathione, and
      macromolecules, reliable quantification of ascorbate (Cramer-Rao lower bounds<0.2
      micromol/g) by LCModel analysis of STEAM (TE=2 ms) spectra was possible at 9.4 T.
      Ascorbate concentrations quantified from the STEAM spectra were in very good
      agreement with concentrations calculated from fully resolved ascorbate resonances
      in MEGA-PRESS-edited spectra measured from identical volumes of interest.
      Ascorbate concentrations measured using STEAM decreased with increasing postnatal
      rat age, in agreement with published brain ascorbate concentrations measured in
      vitro using high-performance liquid chromatography (HPLC).

PMID- 16586454
TI  - The historiography of Swedish sociology and the bounding of disciplinary
      identity.
AB  - Bounding a scientific discipline is a way of regulating its cognitive direction
      as well as its relations to neighboring disciplines and extra-academic
      authorities. In this process of identity making, disciplinary history often is a
      crucial element. In this article, focusing on the historiography of Swedish
      sociology and the reception of Gustaf Steffen, Sweden's first professional
      sociologist, it is argued that Steffen's marginalized role in the traditional
      accounts should be understood not only with reference to his supposed theoretical
      shortcomings, but also in the historical context of the early postwar
      reestablishment of sociology as an academic discipline and its prevalent need for
      a new disciplinary identity, strategically adjusted to the contemporary
      institutional and political settings.

PMID- 16586455
TI  - "A new deal for the drug addict": the Addiction Research Center, Lexington,
      Kentucky.
AB  - This article describes the social organization of knowledge production in the
      formative moments of the substance abuse research enterprise. It describes the
      institutional arrangements and material conditions of a U.S. Public Health
      Service laboratory that was housed in a facility run jointly with the federal
      Bureau of Prisons. The Addiction Research Center (ARC) in Lexington, Kentucky,
      was dedicated to elucidating the basic underlying mechanisms of drug addiction.
      The ARC was housed on the rural campus of a prison-hospital called "Narco," one
      of two "narcotics farms" in Lexington, Kentucky, and Fort Worth, Texas. For its
      studies on drug effects, the ARC had access to a pool of drug-experienced human
      subjects drawn from the ranks of convicted felons. Given their unparalleled
      access to human subjects, the scientists who worked at the ARC made conceptual
      contributions still acknowledged today. Based on archival work as well as dozens
      of oral history interviews with individuals who began their research careers at
      Lexington, the article presents an analytic, intellectual history of the early
      work of Abraham Wikler, whose lifelong pursuit of the underlying mechanisms of
      opiate addiction led him to hypothesize the role of conditioning in relapse, as
      an exemplar of the kind of scientific research that depended on closely listening
      to and observing "post-addicts," as subject participants were called.

PMID- 16586456
TI  - "A gold mine and a tool for democracy": George Gallup, Elmo Roper, and the
      business of scientific polling, 1935-1955.
AB  - "Scientific" public opinion polls arrived on the American scene in 1936.
      Examining the work of opinion surveyors George Gallup and Elmo Roper, this essay
      tracks the early career of a new social scientific technology, one that
      powerfully shaped conceptions of "the public." Pollsters described their craft as
      a democratic one that could accurately represent the U.S. populace. Yet, their
      assumptions about that same public-and the techniques they employed to measure it
      undermined such claims, and even risked calling the polling profession into
      question. To understand why Gallup and Roper fell short of their stated
      ambitions, one must turn not only to the state of midcentury sampling methods but
      also to the corporate sponsors and commercial pressures underlying their
      enterprise.

PMID- 16586457
TI  - Advantages of parallel imaging in conjunction with hyperpolarized helium--a new
      approach to MRI of the lung.
AB  - Hyperpolarized helium (3He) gas MRI has the potential to assess pulmonary
      function. The non-equilibrium state of hyperpolarized 3He results in the
      continual depletion of the signal level over the course of excitations. Under non
      equilibrium conditions the relationship between the signal-to-noise ratio (SNR)
      and the number of excitations significantly deviates from that established in the
      equilibrium state. In many circumstances the SNR increases or remains the same
      when the number of data acquisitions decreases. This provides a unique
      opportunity for performing parallel MRI in such a way that both the temporal and
      spatial resolution will increase without the conventional decrease in the SNR. In
      this study an analytical relationship between the SNR and the number of
      excitations for any flip angle was developed. Second, the point-spread function
      (PSF) was utilized to quantitatively demonstrate the unconventional SNR behavior
      for parallel imaging in hyperpolarized gas MRI. Third, a 24-channel (24ch)
      receive and two-channel (2ch) transmit phased-array system was developed to
      experimentally prove the theoretical predictions with 3He MRI. The in vivo
      experimental results prove that significant temporal resolution can be gained
      without the usual SNR loss in an equilibrium system, and that the entire lung can
      be scanned within one breath-hold (approximately 13 s) by applying parallel
      imaging to 3D data acquisition.

PMID- 16586458
TI  - Linear combination filtering for T2-selective imaging of the knee.
AB  - Recently a novel T2 selective imaging method based on linear combination (LC)
      filtering was developed. By linearly combining images acquired with different
      echo times LC filtering is able to generate images showing only tissues with a
      preselected range of T2 relaxation times. In this study the use of LC filtering
      in knee imaging was investigated. Three LC filters were designed: a short LC
      filter for imaging the knee meniscus, a medium LC filter for articular cartilage,
      and a long LC filter for synovial fluid. To verify the filter designs, eight
      phantoms with different T2 relaxation times were imaged. In addition, in vivo
      images were acquired from four asymptomatic volunteers and a subject with
      cartilage damage. T2 maps were also generated using the same source images.
      Signal-to-noise ratio (SNR) measurements were made of the meniscus, cartilage,
      and fluid regions on the three LC filtered images. The highest SNR was seen in
      the target tissue on each of the LC filtered images. LC filtering is a new method
      that can selectively image knee tissues based on their T2.

PMID- 16586459
TI  - Metabolism of a new P-glycoprotein inhibitor HM-30181 in rats using liquid
      chromatography/electrospray mass spectrometry.
AB  - HM-30181, 4-oxo-4H-chromene-2-carboxylic acid, [2-(2-{4-[2-(6,7-dimethoxy-3,4
      dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl}-2H-tetrazol-5-yl)-4,5
      dimethoxyphenyl]amide, is a new P-glycoprotein inhibitor. This study was
      performed to identify the in vitro and in vivo metabolic pathway of HM-30181 in
      rats. Rat liver microsomal incubation of HM-30181 in the presence of NADPH
      resulted in the formation of four metabolites, M1-M4. M1 and M2 were identified
      as 2-(2-{4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl}-2H
      tetrazol-5-yl)-4,5-dimethoxyaniline and 4- or 5-O-desmethyl-HM-30181,
      respectively, on the basis of liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) analysis with the synthesized authentic standards. M3 and M4 were
      suggested to be 6- or 7-O-desmethyl-HM-30181 and hydroxy-HM-30181, respectively.
      These in vitro metabolites were also detected in feces and urine samples after an
      intravenous administration of HM-30181 to male rats. The metabolic routes for HM
      30181 were O-demethylation of the methoxy group to M2 and M3, hydrolysis of the
      amide group to M1, and hydroxylation to M4.

PMID- 16586460
TI  - A high-performance liquid chromatography/tandem mass spectrometry method for the
      determination of artemisinin in rat plasma.
AB  - Artemisinin is a widely used antimalarial drug. To evaluate the pharmacokinetics
      of artemisinin in rats, a sensitive and specific liquid chromatography/tandem
      mass spectrometric (LC/MS/MS) method was developed and validated for the
      determination of artemisinin in rat plasma. For detection, a Sciex API 4000
      LC/MS/MS instrument with an electrospray ionization (ESI) TurboIonSpray inlet in
      the positive ion multiple reaction monitoring (MRM) mode was used to monitor
      precursor ([M+NH4]+) --> product ions of m/z 300.4 --> 209.4 for artemisinin and
      m/z 316.4 --> 163.4 for artemether, the internal standard (IS). The plasma
      samples were pretreated by a simple liquid-liquid extraction with ether. The
      standard curve was linear (r > 0.99) over the artemisinin concentration range of
      1.0-200.0 ng/mL in plasma. The method had a lower limit of quantification of 1.0
      ng/mL for artemisinin in 100 microL of plasma, which offered a satisfactory
      sensitivity for the determination of artemisinin. The intra- and inter-day
      precisions were measured to be within +/-5.3% and accuracy between -2.6% and 1.2%
      for all quality control samples, lower limit of quantification and upper limit of
      quantification samples. The extraction recoveries of artemisinin and the IS were
      95.4 +/- 4.5% and 92.8 +/- 3.9%, respectively. This present method was
      successfully applied to the characterization of the pharmacokinetic profile of
      artemisinin in rats after oral administration.

PMID- 16586461
TI  - Bioavailability of an extemporaneous suspension of propafenone made from tablets.
AB  - Propafenone is an effective antiarrhythmic agent used in children, while in
      Mexico no specific formulation for children is available, which causes errors in
      adequate dosage. The aim of this study was to determine the bioavailability of a
      suspension prepared extemporaneously using commercial tablets of propafenone. The
      bioavailability was determined in two groups of rabbits (n = 8): the first group
      received a single intravenous dose of 2 mg/kg of propafenone; the second was
      orally administered an extemporaneous suspension of propafenone prepared from
      commercial tablets. Blood samples were drawn at several times during the next 24
      h and analysed by HPLC to determine drug levels. The extemporaneous suspension
      was tested previously with satisfactory results regarding physicochemical and
      microbiologic stability. The area under the curve (AUC) for the i.v. route was
      5600.6 ng/ml.h and for oral administration the AUC was 3327.6 ng/ml.h. The
      bioavailability was calculated at 59.41%. These results are consistent with
      previous reports for solid dosage forms. The propafenone suspension prepared
      extemporaneously using commercial tablets is bioavailable using an animal model;
      nevertheless, it is necessary to carry out human studies either in volunteers or
      in patients to confirm these results.

PMID- 16586462
TI  - Investigation of the potential pharmacokinetic and pharmaco-dynamic drug
      interaction between AHN 1-055, a potent benztropine analog used for cocaine
      abuse, and cocaine after dosing in rats using intracerebral microdialysis.
AB  - PURPOSE: AHN 1-055, a benztropine (BZT) analog, binds with high affinity to the
      dopamine transporter (DAT), possesses behavioral, pharmacokinetic (PK) and brain
      microdialysate dopamine (DA) profiles distinct from cocaine. Accordingly, the
      objectives of this study were to evaluate the pharmacokinetics and dopamine
      release of AHN 1-055, in the presence of cocaine. METHODS: Male Sprague Dawley
      rats ( approximately 300 g) were administered 5 mg/kg of AHN 1-055 and cocaine
      i.v. and blood and brain samples were collected over 36 h. In addition, dialysis
      probes were stereotaxically implanted into the nucleus accumbens and
      extracellular fluid (ECF) DA levels were measured. PK and PD models were used to
      describe the relationship between the AHN 1-055, cocaine and DA levels. RESULTS:
      No significant (p< 0.05) differences were found in the PK parameters of AHN 1-055
      alone (V(dss) = 18.7 l/kg, Cl = 1.8 l/h/kg and t(1/2) = 7.69 h) or AHN 1-055 with
      cocaine (V(dss)=17.4 l/kg, Cl = 1.9 l/h/kg and t(1/2) = 6.82 h). The brain-to
      plasma (B/P) ratios (B/P(AHN 1-055) = 4.8 vs B/P(with cocaine) = 4.4) and half
      lives (t(1/2(AHN 1-055)) = 6.2 h vs t(1/2(cocaine) = )5.6 h for AHN 1-055 alone
      and with cocaine were comparable. AHN 1-055 DA profiles were significantly
      different after co-administration with cocaine. There were no differences in the
      IC(50) for AHN 1-055, with cocaine, however, the IC(50) for cocaine was
      significantly reduced with AHN 1-055. CONCLUSIONS: The PK parameters of AHN 1-055
      were not changed, however, the effect on DA levels was affected when cocaine was
      administered with AHNDA profile is affected when dosed with cocaine. This latter
      effect is a desirable attribute in the development of a medication as a potential
      substitute therapeutic medication for the treatment of cocaine abuse.

PMID- 16586463
TI  - Rat strain differences in stereospecific 2-oxidation of RS-8359, a reversible and
      selective MAO-A inhibitor, by aldehyde oxidase.
AB  - Aldehyde oxidase catalysed 2-oxidation activity of the (S)-enantiomer of RS-8359,
      a selective and reversible monoamine oxidase A (MAO-A) inhibitor, was
      investigated in liver cytosolic fractions from ten rat strains. Remarkably large
      strain differences were observed with approximately a 230 variation between the
      highest activity in the Wistar-Imamichi strain and the lowest activity in the
      Slc:Wistar strain. The activities of Crj:SD and Slc:SD strain rats were
      considerably low, and that of the F344/DuCrj strain was very low. Among six
      Wistar strains, Crj:Wistar, Slc:Wistar, WKY/Izm, WKAH/Hkm, Jcl:Wistar and Wistar
      Imamichi, the Slc:Wistar strain rats showed exceptionally low 2-oxidation
      activity that was comparable to that of the F344/DuCrj strain. The rat strain
      differences in the catalytic activity of aldehyde oxidase could correlate in part
      with the expressed levels of protein based on the mRNA of aldehyde oxidase.
      However, no small discrepancy existed in the almost negligible catalytic activity
      and the fairly high expression levels of protein and mRNA in the F344/DuCrj and
      Slc:Wistar strain rats. Some genetic factors might possibly be one of reasons for
      the discrepancy.

PMID- 16586464
TI  - Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous
      omeprazole in rats.
AB  - A series of experiments using various inducers and inhibitors of the hepatic
      microsomal cytochrome P450 (CYP) isozymes were conducted to find CYP isozymes
      responsible for the metabolism of omeprazole in male Sprague-Dawley rats.
      Omeprazole, 20 mg/kg, was administered intravenously. In rats pretreated with SKF
      525-A (a nonspecific CYP isozyme inhibitor in rats), the time-averaged nonrenal
      clearance (Cl(nr)) was significantly slower (77.1% decrease) than that in
      untreated rats. This indicated that omeprazole is metabolized via CYP isozymes in
      rats. Hence, rats were pretreated with various enzyme inducers and inhibitors. In
      rats pretreated with 3-methylcholanthrene and dexamethasone (main inducers of
      CYP1A1/2 and 3A1/2 in rats, respectively), the Cl(nr) values were significantly
      faster (43.8% and 26.3% increase, respectively). In rats pretreated with
      troleandomycin and quinine (main inhibitors of CYP3A1/2 and 2D1 in rats,
      respectively), the Cl(nr) values were significantly slower (20.9% and 12.9%
      decrease, respectively). However, the Cl(nr) values were not significantly
      different in rats pretreated with orphenadrine, isoniazid and sulfaphenazole
      (main inducers of CYP2B1/2 and 2E1, and a main inhibitor of 2C11, respectively,
      in rats) compared with those of respective control rats. The above data suggested
      that omeprazole could be mainly metabolized via CYP1A1/2, 3A1/2 and 2D1 in male
      rats.

PMID- 16586465
TI  - Initial non-compliance with antihypertensive monotherapy is followed by complete
      discontinuation of antihypertensive therapy.
AB  - PURPOSE: Discontinuation with treatment is a major problem in the treatment of
      hypertension. The objective of our study was to assess the association between
      non-compliance and discontinuation in patients who started using antihypertensive
      monotherapy. METHODS: A nested case-control study within a cohort of new users of
      antihypertensive drugs between 1st January 1999 and 31st December 2002 was
      performed. We used data from the PHARMO database, a record linkage system
      containing drug-dispensing records from community pharmacies and linked hospital
      discharge records of approximately 950,000 subjects. Cases discontinued their use
      of antihypertensive monotherapy and were not switched to other antihypertensive
      treatment, controls stayed on their initially prescribed monotherapy. Conditional
      logistic regression was used to calculate odds ratios (OR) and their 95%
      confidence intervals (CI). RESULTS: In a cohort of 39,714 new users of
      antihypertensive drugs, we identified 9111 cases and 9111 matched controls. The
      percentage of non-compliant patients (compliance < 80%) among cases and controls
      was 14.0% and 5.8%, respectively [OR 2.86 (95%CI: 2.52-3.24)]. Patients who used
      less than 90 days had a higher risk on discontinuation [OR 3.10 (95%CI: 2.67
      3.59)] than patients who used more than 90 days [OR 2.28 (95%CI: 1.79-2.92)]. The
      association was generally similar among males and females, among the different
      types of antihypertensives and among the different age groups. CONCLUSION: In
      patients who start antihypertensive monotherapy, non-compliance is often followed
      by discontinuation of this antihypertensive treatment. The pharmacy medication
      history is a valuable tool for physicians to identify patients who have a high
      risk on discontinuation with antihypertensive treatment.

PMID- 16586466
TI  - Factors associated with the pharmacist counselling without dispensing.
AB  - PURPOSE: To describe the pharmacist counselling without dispensing and to
      analysed the characteristics of pharmacies and pharmacists that provide this type
      of counselling, and the characteristics of customers that receive it to a greater
      extent. METHODS: We carried out a cohort study on a sample of 166 pharmacists in
      North West Spain. Different characteristics of pharmacists and clients and other
      variables related to counselling were measured (who initiates the consultation;
      type of consultation; whether or not the patient consulted with a doctor
      previously and who is the receptor of the counselling) were included in the
      models as independent variables. Pharmacist Counselling without dispensing
      (PhCwD) were included as dependent variable. We constructed logistic regression
      models. RESULTS: The response rate to the first questionnaire was 98.8% and the
      participation rate in the follow-up was 60%. Out of 7010 registered pharmacist
      counselling, 6034 were included in the final analysis (86.1%). The proportion of
      PhCwD is 26.3% (95%IC: 25.2-27.4). CONCLUSIONS: Our results show the number of
      working hours of the pharmacist and the amount of customers are associated with
      PhCwD. So working hours and amount customers should be reduced. Other factor that
      should be taken into account is the fact that pharmacists with less experience
      should give less counsels. Thus during the university period pharmacist
      counselling should be studied. Finally, our results show that an important
      proportion of counselling is given regardless the dispensation process, and this
      should be taken into account when defining the pharmacists remuneration system.

PMID- 16586467
TI  - Spontaneous resolution of prenatally diagnosed dural sinus thrombosis: a case
      report.
AB  - Fetal thrombosis of the dural sinus is an extremely rare congenital
      cerebrovascular condition that is potentially fatal. We report a case of dural
      sinus thrombosis diagnosed by prenatal ultrasonography and fetal magnetic
      resonance imaging (MRI) in the second trimester. The thrombosis showed partial
      resolution during pregnancy and resolved spontaneously after birth without
      neurological complications. This is the first report of spontaneous postnatal
      resolution, and may provide helpful information on the natural history and
      prenatal counseling of fetal thrombosis of the dural sinus.

PMID- 16586468
TI  - Differentiation of estriol glucuronide isomers by chemical derivatization and
      electrospray tandem mass spectrometry.
AB  - This paper describes a way of differentiating between the three isomers of
      estriol glucuronide by the use of chemical derivatization and liquid
      chromatography/electrospray tandem mass spectrometry (MS/MS). In their native
      form, these isomers gave rise to almost identical product ion spectra, involving
      the neutral loss of 176 Da (i.e. monodehydrated glucuronic acid), which made it
      impossible to determine the position of conjugation by MS/MS alone. In order to
      change the fragmentation pathways, positive charges were introduced into the
      analytes by chemical derivatization. The following reagents were tested: 2-chloro
      1-methylpyridinium iodide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 2
      picolylamine. Interestingly, derivatization using a combination of all three
      reagents gave a selective fragmentation pattern that could differentiate between
      the isomers estriol-16-glucuronide and estriol-17-glucuronide. Estriol-3
      glucuronide, which lacks a free phenolic group, could be differentiated through a
      different type of reaction product when exposed to 2-chloro-1-methylpyridinium
      iodide. Furthermore, in order to assist structural assignment of the fragments,
      their accurate masses were determined using a hybrid quadrupole time-of-flight
      mass spectrometer and fragmentation pathways were elucidated by the use of MS3 on
      an ion trap mass spectrometer.

PMID- 16586469
TI  - Characterization of a mini membrane inlet mass spectrometer for on-site detection
      of contaminants in both aqueous and liquid organic samples.
AB  - A mini membrane inlet mass spectrometer (mini-MIMS) of a total weight of 12 kg
      was constructed using a miniature Multipole mass spectrometer, a small vacuum
      system and a flexible flat sheet membrane inlet, where the exposed membrane area
      can be changed by a factor of 80. The variable membrane area together with the
      possibility of operating the Multipole at pressures up to 1 x 10(-3) Torr made it
      possible to test the system with three microporous membranes (cellulose,
      polyether sulfone and polypropylene) normally not compatible with standard
      electron ionization MIMS systems and a standard non-porous polydimethylsiloxane
      membrane. We found that the hydrophilic cellulose and polyether sulfone membranes
      had selectivity characteristics opposite to those of the standard silicone
      membrane. They demonstrated preferential detection of hydrophilic compounds in
      hydrophobic organic solvents, whereas the silicone membrane preferentially
      detects hydrophobic organic compounds in aqueous solution. Using the cellulose
      membrane, organic contaminants and water could be detected in organic solvents at
      10-100 ppm levels by weight, the relative high detection limits primarily caused
      by interference from a high chemical background from the solvent. When being used
      with the standard silicone membrane the mini-MIMS behaved just like most standard
      MIMS systems with detection limits of volatile organic compounds in water at
      concentrations just below 1 ppm. The hydrophobic microporous polypropylene
      membrane was not found to be useful with the mini-MIMS.

PMID- 16586470
TI  - Use of prescription medications with a potential for fetal harm among pregnant
      women.
AB  - PURPOSE: To estimate the prevalence of use of prescription drugs with a potential
      for fetal harm among pregnant women in the United States. METHODS: A
      retrospective study was conducted using the automated databases of eight health
      maintenance organizations involved in the HMO Research Network Center for
      Education and Research on Therapeutics (CERT). Women who delivered an infant from
      January 1996 to December 2000 were identified. The frequency of use of
      prescription drugs with a potential for fetal harm was based upon the expert
      review of a clinical teratologist and the U.S. Food and Drug Administration (FDA)
      risk classification system, assuming a gestational duration of 270 days. RESULTS:
      Among the 114 165 women with no documentation of a diagnosis suggesting potential
      pre-term birth or dispensing of ovulation stimulants in the 270 days before
      delivery, 1305 (1.1%) received a teratogenic drug during the 270 days before
      delivery, based upon the expert review of a clinical teratologist. A larger
      proportion of women received U.S. FDA category D or X drugs (5.8%; N = 6600).
      However, the general patterns of use were similar, with higher use in early
      pregnancy compared to later trimesters. The proportion of women dispensed a
      teratogen during pregnancy was substantially higher among women who received a
      teratogen in the 90 days before pregnancy compared to women who did not (adjusted
      RR = 38.9, 95%CI, 33.5, 45.3). CONCLUSIONS: Our results suggest that further
      efforts directed at physicians to counsel women or at the women themselves about
      the potential risks of particular medications appear warranted.

PMID- 16586471
TI  - Derivatization by 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate for enhancing
      the ionization yield of small peptides and glycopeptides in matrix-assisted laser
      desorption/ionization and electrospray ionization mass spectrometry.
AB  - The characterization of glycosylation in proteins by mass spectrometry (MS) is
      often impeded by strong suppression of ionization of glycopeptides in the
      presence of non-glycosylated peptides. Glycopeptides with a large carbohydrate
      part and a short peptide backbone are particularly affected by this problem. To
      meet the goal of generating mass spectra exhibiting glycopeptide coverages as
      complete as possible, derivatization of glycopeptides offers a practical way to
      increase their ionization yield. This paper investigated derivatization with 6
      aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) which is a rapid labeling
      technique commonly used for fluorescence detection in high-performance liquid
      chromatography (HPLC) and capillary electrophoresis (CE). As test samples we used
      peptides and glycopeptides obtained by enzymatic digestion of three different
      glycoproteins, i.e., human antithrombin, chicken ovalbumin, and bovine alpha1
      acid-glycoprotein. It was found that AQC derivatization resulted in strongly
      increased signal intensities when analyzing small peptides and glycopeptides by
      matrix-assisted laser desorption/ionization (MALDI)-MS. For these compounds the
      limit of detection could be reduced to low fmol amounts. Without derivatization
      only glycopeptides containing large peptide backbones were detected by MALDI-MS.
      This effect was even significant when glycopeptides were pre-separated and
      enriched by means of lectin affinity chromatography before MALDI-MS analysis and
      when using electrospray ionization (ESI). This labeling method, applied in
      combination with MS detection for the first time, was found to be well suited for
      the enhancement of detection sensitivity for small glycopeptides in MALDI-MS
      analysis and thus for reducing the need for pre-separation steps.

PMID- 16586472
TI  - Accurate neurosonographic prediction of brain injury in the surviving fetus after
      the death of a monochorionic cotwin.
AB  - OBJECTIVE: To assess the feasibility of the prenatal diagnosis using fetal
      neurosonography of brain injuries in the surviving fetus after the demise of a
      monochorionic cotwin. METHODS: This was a retrospective observational study in
      the period 1990-2004 of monochorionic twin pregnancies with a single fetal
      demise. A detailed sonographic evaluation of the intracranial anatomy of the
      surviving twin had been performed whenever possible using a multiplanar approach
      and from 1999, fetal magnetic resonance imaging was offered as well. Postnatal
      follow-up was obtained in all cases. RESULTS: In six of nine cases, abnormal
      neurosonographic findings were identified including intracranial hemorrhage,
      brain atrophy, porencephaly and periventricular echogenicities evolving into
      polymicrogyria. Prenatal diagnosis of brain lesions was confirmed postnatally and
      all affected infants who survived had severe neurological sequelae. Two fetuses
      had normal cerebral structures both on the prenatal neurosonogram and on
      postnatal imaging and were following normal developmental milestones, one at 1
      and the other at 5 years of age. In one case the neurosonographic examination was
      suboptimal and the infant was found at birth to have a porencephalic cyst. Fetal
      magnetic resonance imaging was performed in two cases and confirmed the
      ultrasound diagnosis. CONCLUSIONS: Prenatal neurosonography is a valuable tool
      for the prediction of neurological outcome in fetuses surviving after the
      intrauterine death of a monochorionic cotwin. Although our experience is limited,
      we suggest that magnetic resonance imaging should also be offered.

PMID- 16586473
TI  - Relationship between lung-to-head ratio and lung volume in normal fetuses and
      fetuses with diaphragmatic hernia.
AB  - OBJECTIVE: To examine the relationship between the fetal lung area and lung area
      to head circumference ratio (LHR) and lung volume by three-dimensional (3D)
      ultrasonography in normal fetuses and in fetuses with unilateral congenital
      diaphragmatic hernia (CDH). METHODS: In 64 fetuses with CDH at median 26 (range,
      20-32) weeks of gestation the contralateral lung volume, lung area and LHR were
      measured and the values were compared to those of 650 normal fetuses at 12-32
      weeks. In the normal fetuses both lungs were assessed but in the 64 fetuses with
      CDH only the contralateral lung was measured because the ipsilateral lung could
      be visualized adequately in only 40 (62.5%) of the cases. Regression analysis was
      used to assess the significance of the association between lung volume and lung
      area or LHR. In the fetuses with CDH, the observed to expected ratios for lung
      area and LHR were calculated. The expected lung area and LHR were the normal
      median for a given lung volume. The significance of the differences between the
      observed to expected lung area and LHR in fetuses with CDH and normal fetuses was
      determined. In the 64 fetuses with CDH and in 64 normal fetuses, matched for
      gestational age, the lung length between the apex and the superior aspect of the
      diaphragm dome was also recorded. RESULTS: In normal fetuses the median lung area
      and LHR in both the left and right lungs increased significantly with lung
      volume. In the fetuses with CDH, the lung area and lung volume for gestation were
      substantially lower than in normal fetuses and the ratios of observed to expected
      lung area and LHR for a given lung volume were significantly lower than the
      respective values in normal fetuses. Additionally, the mean lung length was 13%
      greater and the mean lung area was 44% smaller than the respective values in the
      normal controls matched for gestational age. CONCLUSIONS: The finding of a
      significant association between LHR and lung volume has validated the use of LHR
      in the assessment of lung growth. However, the study has also demonstrated that
      in fetuses with CDH, LHR underestimates the actual lung volume, because the
      herniated viscera cause a greater lateral, rather than vertical, compression of
      the contralateral lung.

PMID- 16586474
TI  - Examination of the fetal brain by transabdominal three-dimensional ultrasound:
      potential for routine neurosonographic studies.
AB  - OBJECTIVE: To evaluate the role of transabdominal three-dimensional (3D)
      ultrasound in the assessment of the fetal brain and its potential for routine
      neurosonographic studies. METHODS: We studied prospectively 202 consecutive
      fetuses between 16 and 24 weeks' gestation. A 3D ultrasound volume of the fetal
      head was acquired transabdominally. The entire brain anatomy was later analyzed
      using the multiplanar images by a sonologist who was expert in neonatal cranial
      sonography. The quality of the conventional planes obtained (coronal, sagittal
      and axial, at different levels) and the ability of the 3D multiplanar neuroscan
      to visualize properly the major anatomical structures of the brain were
      evaluated. RESULTS: Acceptable cerebral multiplanar images were obtained in 92%
      of the cases. The corpus callosum could be seen in 84% of the patients, the
      fourth ventricle in 78%, the lateral sulcus (Sylvian fissure) in 86%, the
      cingulate sulcus in 75%, the cerebellar hemispheres in 98%, the cerebellar vermis
      in 92%, the medulla oblongata in 97% and the cavum vergae in 9% of them. The
      thalami and the cerebellopontine cistern (cisterna magna) were identified in all
      cases. At or beyond 20 weeks, superior visualization (in > 90% of cases) was
      achieved of the cerebral fissures, the corpus callosum (97%), the supracerebellar
      cisterns (92%) and the third ventricle (93%). Some cerebral fissures were seen
      initially at 16-17 weeks. CONCLUSION: Multiplanar images obtained by
      transabdominal 3D ultrasound provide a simple and effective approach for detailed
      evaluation of the fetal brain anatomy. This technique has the potential to be
      used in the routine fetal anomaly scan.

PMID- 16586475
TI  - The use of recently described ionisation techniques for the rapid analysis of
      some common drugs and samples of biological origin.
AB  - Three ionisation techniques that require no sample preparation or extraction
      prior to mass analysis have been used for the rapid analysis of pharmaceutical
      tablets and ointments. These methods were (i) the novel direct analysis in real
      time (DART), (ii) desorption electrospray ionisation (DESI), and (iii) desorption
      atmospheric pressure chemical ionisation (DAPCI). The performance of the three
      techniques was investigated for a number of common drugs. Significant differences
      between these approaches were observed. For compounds of moderate to low polarity
      DAPCI produced more effective ionisation. Accurate DESI and DAPCI tandem mass
      spectra were obtained and these greatly enhance the selectivity and information
      content of the experiment. The detection from human skin of the active
      ingredients from ointments is reported together with the detection of ibuprofen
      metabolites in human urine.

PMID- 16586477
TI  - Diagnosis of midline anomalies of the fetal brain with the three-dimensional
      median view.
AB  - OBJECTIVE: To investigate the effectiveness of a simplified approach to the
      evaluation of the midline structures of the fetal brain using three-dimensional
      (3D) ultrasound. METHODS: Sonographic examinations were performed in normal
      fetuses and in cases with anomalies involving the midline cerebral structures.
      Two-dimensional (2D) median planes were obtained by aligning the transducer with
      the anterior fontanelle and midline sutures by either transabdominal or
      transvaginal scans. Median planes were also reconstructed using 3D
      ultrasonography from volumes acquired from transabdominal axial planes of the
      fetal head (3D median planes), by either multiplanar analysis of static volumes
      or volume contrast imaging in the coronal plane (VCI-C). 2D and 3D median planes
      were compared qualitatively and quantitatively by measuring the corpus callosum
      and cerebellar vermis. RESULTS: 2D median planes could be visualized in 54/56
      normal fetuses. 3D median planes were obtained in all, usually more easily and
      rapidly. There was a good correlation between 2D and 3D images. Measurements of
      the corpus callosum and cerebellar vermis were highly correlated, with mean
      variations of 6% and 14%, respectively. The abnormal group included 13 fetuses
      (five with partial or complete agenesis of the corpus callosum, six with
      posterior fossa malformations, two with a combination of these two anomalies). In
      all cases the diagnosis could be made by both 2D and 3D views and was always
      confirmed by postnatal investigation. Although 2D median views were of better
      quality, 3D images were always adequate for diagnosis, both in normal and
      abnormal fetuses. CONCLUSIONS: 3D median planes are obtained more easily than 2D
      ones, and allow an accurate diagnosis of normal cerebral anatomy and anomalies.
      The 3D approach may be valuable particularly for rapid assessment of fetal
      cerebral anatomy in standard examinations.

PMID- 16586478
TI  - Development of a liquid chromatography/time-of-flight mass spectrometric method
      for the simultaneous determination of trichothecenes, zearalenone and aflatoxins
      in foodstuffs.
AB  - A liquid chromatography/atmospheric pressure chemical ionization mass
      spectrometry (LC/APCI-MS) method based on time-of-flight MS (TOFMS) with a real
      time reference mass correction technique was developed for the simultaneous
      determination of Fusarium mycotoxins (nivalenol, deoxynivalenol, fusarenon X, 3
      acetyldeoxynivalenol, 15-acetyldeoxynivalenol, HT-2 toxin, T-2 toxin,
      diacetoxyscirpenol, zearalenone) and Aspergillus mycotoxins (aflatoxin B1,
      aflatoxin B2, aflatoxin G1, aflatoxin G2) in corn, wheat, cornflakes and
      biscuits. Samples were cleaned up with a MultiSep #226 column. Detection of the
      mycotoxins was carried out in exact mass chromatograms with a mass window of 0.03
      Th. Calibration curves were linear from 2 to 200 ng x mL(-1) for trichothecenes
      and zearalenone, and 0.2 to 20 ng x mL(-1) for aflatoxins, by 20 microL
      injection. The limits of detection ranged from 0.1 to 6.1 ng x g(-1) in
      foodstuffs analyzed in this study. The LC/TOFMS method was found to be suitable
      for the screening of multiple mycotoxins in foodstuffs rapidly and with high
      sensitivity, and its performance was demonstrated for the confirmation for target
      mycotoxins.

PMID- 16586479
TI  - Left and right lung volumes in fetuses with diaphragmatic hernia.
AB  - OBJECTIVE: To compare the volume of the ipsilateral and contralateral lungs in
      fetuses with congenital diaphragmatic hernia (CDH). METHODS: Left and right lung
      volumes were measured using three-dimensional (3D) ultrasonography in 42 fetuses
      with CDH at median 26 (range, 20-32) weeks of gestation. Each value was then
      expressed as a difference, in standard deviations, from the normal mean for
      gestation, previously established from the study of 650 normal fetuses at 12-32
      weeks (Z-score). The Mann-Whitney U-test was used to determine the significance
      of the differences between the measurements in fetuses with CDH and normal
      fetuses and between the ipsilateral and contralateral lungs in fetuses with left-
      and right-sided CDH. RESULTS: There were 34 fetuses with left-sided CDH and eight
      with right-sided CDH. In CDH both the ipsilateral and contralateral lung volumes
      were substantially lower than in normal fetuses. In left CDH the left lung volume
      was 4.03 (median; range, 3.11-4.78) SDs below the normal mean for gestation, and
      the respective values for the right lung were 3.04 (median; range, 1.78-4.31) SDs
      (P < 0.001 for both). In right CDH, the left lung volume was 2.91 (median; range,
      1.62-4.07) SDs below the normal mean for gestation and the respective values for
      the right lung were 4.35 (median; range, 3.07-4.99) SDs (P < 0.001 for both). In
      both left and right diaphragmatic hernia the deficit in the volume of the
      ipsilateral lung was significantly greater than the deficit in the contralateral
      lung. CONCLUSIONS: In fetuses with CDH both the ipsilateral and contralateral
      lung volumes are substantially lower than in normal fetuses.

PMID- 16586480
TI  - Prenatal diagnosis of campomelic dysplasia with three-dimensional ultrasound.

PMID- 16586481
TI  - Analysis of fluorescence from algae fossils of the Neoproterozoic Doushantuo
      formation of China by confocal laser scanning microscope.
AB  - Chinese algae fossils can provide unique information about the evolution of the
      early life. Thin sections of Neoproterozoic algae fossils, from Guizhou, China,
      were studied by confocal laser scanning microscopy, and algae fossils were
      fluorescenced at different wavelengths when excited by laser light of 488 nm, 476
      nm, and 568 nm wavelength. When illuminated by 488 nm laser light, images of the
      algae fossils were sharper and better defined than when illuminated by 476 nm and
      568 nm laser light. The algae fossils fluoresce at a wide range of emission
      wavelengths. The three-dimensional images of the fluorescent algae fossils were
      compared with the transmission images taken by light microscope. We found that
      the fluorescence image of the confocal laser scanning microscope in a single
      optical section could pass for the transmission image taken by a light
      microscope. We collected images at different sample depths and made a three
      dimensional reconstruction of the algae fossils. And on the basis of the
      reconstruction of the three-dimensional fluorescent images, we conclude that the
      two algae fossils in our present study are red algae.

PMID- 16586482
TI  - Composition of nasal airway surface liquid in cystic fibrosis and other airway
      diseases determined by X-ray microanalysis.
AB  - The ionic composition of the airway surface liquid (ASL) in healthy individuals
      and in patients with cystic fibrosis (CF) has been debated. Ion transport
      properties of the upper airway epithelium are similar to those of the lower
      airways and it is easier to collect nasal ASL from the nose. ASL was collected
      with ion exchange beads, and the elemental composition of nasal fluid was
      determined by X-ray microanalysis in healthy subjects, CF patients, CF
      heterozygotes, patients with rhinitis, and with primary ciliary dyskinesia (PCD).
      In healthy subjects, the ionic concentrations were approximately isotonic. In CF
      patients, CF heterozygotes, rhinitis, and PCD patients, [Na] and [Cl] were
      significantly higher compared when compared with those in controls. [K] was
      significantly higher in CF and PCD patients compared with that in controls.
      Severely affected CF patients had higher ionic concentrations in their nasal ASL
      than in patients with mild or moderate symptoms. Female CF patients had higher
      levels of Na, Cl, and K than male patients. As higher salt concentrations in the
      ASL are also found in other patients with airway diseases involving chronic
      inflammation, it appears likely that inflammation-induced epithelial damage is
      important in determining the ionic composition of the ASL.

PMID- 16586483
TI  - Distinguishing the medicinal herb Oldenlandia diffusa from similar species of the
      same genus using fluorescence microscopy.
AB  - The light microscope is routinely used for microscopic identification of Chinese
      Materia Medica (CMM). However, the fluorescence microscope has not been used for
      this purpose until now. The CMM, Baihuasheshecao, mostly used as a component of
      herb tea, is a well known folk-medicine in China. According to the Chinese
      Pharmacopoeia, its source is the species Oldenlandia diffusa (Willd.) Roxb. Two
      other species of the same genus, namely O. corymbosa (L.) Lam and O. tenelliflora
      Bl., had been found in use as Baihuasheshecao. To find a quick and easy method to
      distinguish O. diffusa from these similar species of the same genus, the
      fluorescence microscope was used to investigate the fluorescence emission
      characteristics of the three tissues, which were compared with light microscopy
      images of the same material. The results showed that some tissues of the three
      herbs emit autofluorescence. Specially, the wall of endoderm cells of O. diffusa
      and O. tenelliflora emit autofluorescence, while similar tissue of O. corymbosa
      does not. Hence, fluorescence microscopy can be helpful in the identification of
      CMM.

PMID- 16586484
TI  - Leishmaniosis--a report about the microvascular and cellular architecture of the
      infected spleen in Canis familiaris.
AB  - Leishmaniosis is an anthropozoonosis caused by an intracellular protozoan
      parasite that causes a wide spectrum of diseases in humans and dogs worldwide. In
      the Mediterranean basin, Portugal, Central and South America, and in the Middle
      East, visceral leishmaniosis is caused by Leishmania infantum. In these areas,
      dogs are believed to be the natural reservoirs of this parasite. In the case of
      visceral leishmaniosis, the spleen is one of the several hematopoietic and
      immunocompetent organs involved. Since this viscera is a blood filter, the
      authors investigated the expression of the morphological and microvascular
      environment and modifications of the spleen cell population related to
      immunological responses to this parasitic condition. The tools used to perform
      this study were scanning electronic microscopy of intact tissue and corrosion
      casts, transmission electronic microscopy, histology and immunohistochemistry.
      The results reveal three important modifications concerning the spleen's
      microvascular architecture when compared with its normal pattern, independently
      of the serological titer obtained with indirect immunofluorescence. (1) A marked
      scarcity of the sinusoidal system sheet that surrounds the central
      artery/arteriole of the white pulp; (2) A huge development of pulp venules and
      veins; (3) The presence of a surprising development of reticular fibers. The
      authors postulate that independent of the virulence of the parasite involved and
      the type of immunity prevalent in a particular host, the spleen develops blood
      dynamic conditions that permit reduction in the speed of blood flow so that cells
      involved in immunological processes can proliferate and differentiate, and also
      contributes to trapping lymphocytes within the area through the differentiation
      of characteristics that resemble those of HEV endothelial cells.

PMID- 16586486
TI  - Richardson-Lucy algorithm with total variation regularization for 3D confocal
      microscope deconvolution.
AB  - Confocal laser scanning microscopy is a powerful and popular technique for 3D
      imaging of biological specimens. Although confocal microscopy images are much
      sharper than standard epifluorescence ones, they are still degraded by residual
      out-of-focus light and by Poisson noise due to photon-limited detection. Several
      deconvolution methods have been proposed to reduce these degradations, including
      the Richardson-Lucy iterative algorithm, which computes maximum likelihood
      estimation adapted to Poisson statistics. As this algorithm tends to amplify
      noise, regularization constraints based on some prior knowledge on the data have
      to be applied to stabilize the solution. Here, we propose to combine the
      Richardson-Lucy algorithm with a regularization constraint based on Total
      Variation, which suppresses unstable oscillations while preserving object edges.
      We show on simulated and real images that this constraint improves the
      deconvolution results as compared with the unregularized Richardson-Lucy
      algorithm, both visually and quantitatively.

PMID- 16586485
TI  - Comparative analysis of dental enamel polyvinylsiloxane impression and
      polyurethane casting methods for SEM research.
AB  - Dental casting is a very common procedure for making high-quality replicas of
      paleo-anthropological remains. Replicas are frequently used, instead of original
      remains, to study both fossil and extant Primate teeth in morphological and
      metrical analyses. Several commercial products can be used in molds. This study
      analyzed SEM image resolution and enamel surface feature definition of tooth
      molds at various magnification levels and obtained, with both Coltene and 3M low
      viscosity body polyvinylsiloxane impression, materials and polyurethane casts.
      Results, through comparison with the original teeth, show that both the negative
      molds and the positive casts are highly reliable in replicating enamel surfaces.
      However, positive cast quality is optimal for SEM observation only till the
      fourth consecutive replica from the original mold, especially at high SEM
      magnification levels.

PMID- 16586487
TI  - In-situ thickness measurement of porous alumina by atomic force microscopy and
      the reflectance wavelength measurement from 400-1000 nm.
AB  - This article presents a novel method to measure the in situ thickness of porous
      alumina (PA) films. The PA films were prepared in oxalic acid at 30, 40, and 60 V
      direct current. Based on the atomic force microscope measurements, PA film
      porosities and refractive indexes measurements were acquired. With the
      observation of the reflectance spectra of PA films over the wavelength range 400
      1000 nm, the nondestructive thickness measurement of the PA films were accurate
      and were found to be 3.66, 7.76, and 11.38 mum, respectively. Experiments showed
      that when the applied voltage increased, the pores diameters and interpore
      distances were enlarged, and the interference pattern was stronger and exhibited
      a greater number of oscillations over the given wavelength range, which indicated
      that the PA film's thickness increased. Our results match with the theoretical
      predictions and analysis quite well.

PMID- 16586489
TI  - Dynamic study of intramembranous particles in human fresh erythrocytes using an
      "in vitro cryotechnique".
AB  - For analyses of dynamic ultrastructures of erythrocyte intramembranous particles
      (IMPs) in situ, a quick-freezing method was used to stabilize the flow behavior
      of erythrocytes embedded in vitreous ice. Fresh human blood was jetted at various
      pressures through artificial tubes, in which the flowing erythrocytes were
      elongated from biconcave discoid shapes to elliptical ones, and quickly frozen in
      liquid isopentane-propane cryogen (-193 degrees C). They were freeze-fractured
      using a scalpel in liquid nitrogen, and routinely prepared for replica membranes.
      Many IMPs were observed on the protoplasmic freeze-fracture face (P-face) of the
      erythrocyte membranes. Some control erythrocytes under nonflowing or stationary
      conditions showed IMPs with their random distribution. However, other jetted
      erythrocytes under flowing conditions showed variously sized IMPs with much
      closer distribution. They were also arranged into parallel rows in some parts,
      and aggregated together. This quick-freezing method enabled for the first time
      the visualization of time-dependent topology and the molecular alteration of IMPs
      in dynamically flowing erythrocytes.

PMID- 16586488
TI  - Immunogold detection of types I and II chondrocyte collagen fibrils: an in situ
      atomic force microscopic investigation.
AB  - Chondrocyte tissue engineering is a major challenge in the field of cartilage
      repair. The phenotype of chondrocytes consists of cartilage specific proteoglycan
      and type II collagen. During serial passages, chondrocytes dedifferentiate into
      cells, presenting a fibroblast-like phenotype consisting predominately of type I
      collagen synthesis. Observation of native collagen fibers could be visualized by
      atomic force microscope. Here, we developed an original and useful atomic force
      microscopy-based immunogold technique allowing biochemical distinction between
      types I and II collagen fibers. Imaging of 40-nm gold particles staining collagen
      fibers was performed in tapping mode. Rat 1 fibroblasts and human chondrosarcoma
      cells were used as positive models for types I and II collagen, respectively. As
      demonstrated by our data, primary rat chondrocytes adhering for 48 h on a glass
      substrate synthesize type II collagen native fibers. This technique allows
      analyses of local areas of the extracellular matrix of fixed cells, providing
      complementary data about cartilage phenotype. This simple approach could be of
      major interest for the biologist community in routine laboratory investigations,
      to localize in situ, macromolecules of the extracellular matrix.

PMID- 16586490
TI  - Postembryonic development of hard jaws (trophi) in a species belonging to the
      Brachionus plicatilis complex (Rotifera, Monogononta): a morphometric analysis.
AB  - The presence of hard jaws (trophi), with species-specific shape and size, is a
      taxonomic feature of Rotifera, a group of microscopic metazoans. Since trophi are
      used to discriminate among species, it is important to know whether these
      structures change in taxonomically important ways during postembryonic
      development. Using both SEM and optical images, we analyzed more than 100
      individuals of a single clonal lineage of a monogonont rotifer, Brachionus
      plicatilis, in order to describe body and trophi development after hatching. Body
      size, expressed as lorica width and length, was isometrically related to age of
      the animals only during preadult stages. Trophi size, expressed as length of the
      different parts, was unrelated to either age or body size. Therefore, trophi
      elements do not grow after hatching in B. plicatilis. Despite the dimensional
      invariance with age, some differences in trophi size among individuals of the
      same clone were recorded. No difference in left-right asymmetry of the trophi was
      shown; the asymmetric elements of the trophi named rami consistently had the
      right ramus longer than the left. This constancy is in contrast to the reported
      trophi asymmetries in bdelloid rotifers, in which left-right asymmetries are not
      constant within clonal lineages. In conclusion, we suggest that also trophi size,
      constant within the analyzed clone, may be used as an additional taxonomic
      feature to help in the discrimination of taxa within the B. plicatilis complex of
      cryptic species.

PMID- 16586491
TI  - An autonomous phase-boundary detection technique for colloidal hard sphere
      suspension experiments.
AB  - Colloidal suspensions of monodisperse spheres are used as physical models of
      thermodynamic phase transitions and as precursors to photonic band gap materials.
      Current techniques for identifying the phase boundaries involve manually
      identifying the phase transitions, which is very tedious and time-consuming. In
      addition, current image analysis techniques are not able to distinguish between
      densely packed phases within conventional microscope images, which are mainly
      characterized by degrees of randomness or order with similar grayscale value
      properties. We have developed an intelligent machine vision technique that
      automatically identifies colloidal phase boundaries. The technique utilizes
      intelligent image processing algorithms that accurately identify and track phase
      changes vertically or horizontally for a sequence of colloidal hard sphere
      suspension images. This technique is readily adaptable to any imaging application
      wherein regions of interest are distinguished from the background by differing
      patterns of motion over time.

PMID- 16586492
TI  - Insulin-like growth factor binding protein-4 (IGFBP-4) is a novel anti-angiogenic
      and anti-tumorigenic mediator secreted by dibutyryl cyclic AMP (dB-cAMP)
      differentiated glioblastoma cells.
AB  - cAMP has been shown to reverse the transformed phenotype of various cancer cells.
      Human glioblastoma U87MG cells exposed to 500 microM dB-cAMP for 6 days showed
      reduced proliferation, attenuated invasiveness, and inability to induce
      angiogenic responses in human brain endothelial cells (HBECs) grown in
      Matrigeltrade mark. VEGF was the principal mediator of angiogenic actions of
      U87MG conditioned media (CM), since VEGF neutralizing antibody completely
      inhibited U87MG-induced angiogenic responses and no detectable levels of IGF,
      bFGF, and PlGF were found in U87MG CM. VEGF release was induced ( approximately
      20%) in dB-cAMP-treated U87MG cells, suggesting a simultaneous induction of anti
      angiogenic mediators. Down-stream effectors of dB-cAMP actions in U87MG were
      investigated by microarray gene expression analysis. Detected increases in
      differentiation genes, staniocalcin-1 and Wnt-5a, and angiogenesis-related genes,
      PAI-1, SPARC, IGFBP-4, IGFBP-7, PAPP-A, and PRSS-11 in dB-cAMP-treated U87MG
      cells were validated by real-time PCR, Western blot, and/or ELISA. A subsequent
      series of experiments identified IGFBP-4 as the principal anti-angiogenic
      mediator secreted by glioblastoma cells in response to dB-cAMP. Human recombinant
      IGFBP-4 inhibited the angiogenic response of HBEC induced by U87MG CM, whereas
      anti-human IGFBP-4 antibody restored the pro-angiogenic activity of dB-cAMP
      treated U87MG CM. Since neither U87MG nor HBEC cells secreted detectable levels
      of IGF-I, and there are no known cellular IGFBP-4 receptors, the anti-angiogenic
      effect of IGFBP-4 was likely IGF-I-independent and indirect. IGFBP-4 also
      antagonized angiogenic effects of VEGF(165), PlGF, and bFGF, and reduced U87MG
      colony formation in soft-agar. IGFBP-4 is a novel dB-cAMP-induced anti-angiogenic
      and anti-tumorigenic mediator that may be a promising candidate for glioblastoma
      therapy.

PMID- 16586493
TI  - Induction of chemokine and cytokine genes in astrocytes following infection with
      Theiler's murine encephalomyelitis virus is mediated by the Toll-like receptor 3.
AB  - Theiler's murine encephalomyelitis virus (TMEV) infection in the central nervous
      system (CNS) induces a demyelinating disease similar to human multiple sclerosis.
      TMEV infection results in activation of various chemokine and cytokine genes that
      are important in the initiation of an inflammatory response. We have previously
      shown that the production of these chemokines and cytokines in astrocytes is
      induced via the NF-kappaB pathway following TMEV and Coxsackie virus infection.
      In this study, we investigated whether the NF-kappaB-dependent inflammatory
      responses after TMEV infection is triggered through TLR3 and/or TLR7. The
      activation of NF-kappaB or IRF/ISRE, as well as the production of both MCP-1/CCL2
      and IL-8/CXCL8, was observed in only TLR3-transfected HEK 293 cells, but not in
      TLR7-tranfected cells. The potential involvement of TLR3 in mouse embryonic
      fibroblasts and primary astrocytes was further investigated following
      transfection with wildtype or dominant negative form of TLRs and MyD88, as well
      as astrocytes from TLR3- and MyD88-deficient mice. Similarly, the activation of
      transcription factors and chemokine genes is induced in these mouse cells through
      primarily TLR3 signaling pathway, but not TLR7 or other MyD88-mediated pathways
      following TMEV infection. However, the TLR3-mediated cellular activation does not
      appear to affect the level of viral replication in astrocytes. These results
      strongly suggest that TLR3-signaling by TMEV alone is sufficient to induce the
      initial inflammatory cytokine responses that could be very important for the
      outcome of virus-induced encephalitis and/or demyelinating diseases, such as
      multiple sclerosis.

PMID- 16586494
TI  - Genetic mapping of a putative tumor suppressor locus that influences
      tumorigenesis and metastasis in mice.
AB  - The tumor suppressor TP53 is mutated in approximately 70% of Li-Fraumeni syndrome
      (LFS) families; however, other genes may lead to the predisposition to tumors in
      other families. We developed a mouse model to search for other tumor suppressors
      that may be involved in the syndrome. Inbred CE/J mice, which succumb to multiple
      types of tumors similar to those found in LFS, were crossed with the Trp53-null
      129-Trp53tm1Tyj mouse. We monitored the tumor onset and type and found a
      significant earlier tumor onset in the CE/J:129-Trp53tm1Tyj mice compared with
      129-Trp53tm1Tyj mice with a Trp53-null allele. Additionally, in CE/J:129
      Trp53tm1Tyj-Trp53+/- mice, the tumors metastasize, which does not occur in other
      strains of mice. Using simple-sequence length polymorphism analysis for loss of
      heterozygosity in tumors, we identified a putative tumor suppressor locus within
      1 cM on mouse chromosome 11, which encompasses 12 mapped genes.

PMID- 16586495
TI  - Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein
      in patients with previously treated chronic lymphocytic leukemia.
AB  - BACKGROUND: The safety and efficacy of the interleukin-2 diphtheria toxin fusion
      protein (DAB(389)IL2; denileukin diftitox) directed against the IL-2 receptor (IL
      2R) was tested in patients with recurrent or refractory chronic lymphocytic
      leukemia (CLL). METHODS: Denileukin diftitox was administered as 60-minute
      intravenous infusions for 5 days every 21 days at a dose of 18 mug/kg per day for
      up to 8 cycles. In total, 28 patients were treated in 2 multiinstitutional
      studies with similar eligibility criteria and treatment protocols. Twenty-two
      patients receive > or = 2 cycles of denileukin diftitox and were evaluable for
      response. RESULTS: Twelve of 22 patients achieved reductions of peripheral CLL
      cells, with 5 of 12 patients achieving >80% reductions. Six of 22 patients
      achieved reductions in the size of lymph node on examination and computed
      tomography scans, and all 6 of those patients met the criteria for a partial or
      complete response that lasted > or = 2 months. Bone marrow biopsies before and
      after treatment confirmed a complete remission that lasted for 1 year in 1
      patient. Overall, denileukin diftitox produced complete remission in 1 of 22
      patients (4%) and partial remission in 5 of 22 patients (23%) for a total
      remission rate of 27%. Progression-free intervals in the responders were 2 months
      in 2 patients and 4 months, 6 months, 7 months, and 12 months in 1 patient each.
      Toxicities were moderate. No infections associated with immunosuppression were
      seen. There was no significant correlation of response or toxicities with the
      numbers of denileukin diftitox cycles received or with CD25 levels. CONCLUSIONS:
      Follow-up studies will be required to identify predictors of response that may
      improve the response rate to denileukin diftitox in patients with CLL.

PMID- 16586497
TI  - Patterns of exercise across the cancer trajectory in brain tumor patients.
AB  - BACKGROUND: Exercise may represent a supportive intervention that may complement
      existing neurooncologic therapies and address a multitude of therapy-induced
      debilitating side effects in patients with brain tumors. Given the limited
      evidence, the authors conducted a survey to examine the exercise patterns of
      brain tumor patients across the cancer trajectory. METHODS: Using a cross
      sectional design, 386 brain tumor patients who received treatment at the Brain
      Tumor Center at Duke University were sent a questionnaire that assessed self
      reported exercise behavior prior to diagnosis, during adjuvant therapy, and after
      the completion of therapy. RESULTS: The response rate was 28% (106 of 383
      patients). Descriptive analyses indicated that 42%, 38%, and 41% of participants,
      respectively, met national exercise prescription guidelines prior to diagnosis,
      during treatment, and after the completion of adjuvant therapy. Repeated measures
      analyses indicated no significant changes in the majority of exercise behavior
      outcomes over the cancer trajectory. However, exploratory analyses indicated that
      males and younger participants may be at the greatest risk of reducing exercise
      levels after a brain tumor diagnosis. These analyses remained unchanged after
      controlling for relevant demographic and medical covariates. CONCLUSIONS: A
      relatively high percentage of brain tumor patients are exercising at recommended
      levels across the cancer trajectory. Moreover, these patients have unique
      exercise patterns that may be modified by select demographic variables. This
      preliminary study provides important informative data for future studies
      examining the potential role of exercise in patients diagnosed with neurologic
      malignancies.

PMID- 16586496
TI  - International study on low-grade primary central nervous system lymphoma.
AB  - OBJECTIVE: The aim of this study was to characterize the clinical presentation,
      course, and outcome of low-grade primary central nervous system lymphoma.
      METHODS: Cases were assessed in a retrospective series collected from 18 cancer
      centers in 5 countries. RESULTS: Forty patients (18 men, 22 women; median age, 60
      years [range, 19-78]) were identified. Involvement of a cerebral hemisphere or
      deeper brain structures was seen in 37 patients, only leptomeningeal involvement
      in 2 patients, and spinal cord disease in 1 patient. Chemotherapy/radiotherapy
      was conducted in 15 patients, radiotherapy alone in 12, chemotherapy alone in 10,
      and tumor resection alone in 2, whereas 1 patient received no treatment. The
      median progression-free, disease-specific, and overall survival were 61.5 (range,
      0-204), 130 (range, 1-204), and 79 (range, 1-204) months, respectively. Only age
      60 years or older was associated with shorter progression-free (p = 0.009),
      disease-specific (p = 0.015), and overall survival (p = 0.001) in multivariate
      analysis. INTERPRETATION: Low-grade primary central nervous system lymphoma
      differs from the high-grade subtype in its pathological, clinical, and
      radiological features. It has a better long-term outcome than primary central
      nervous system lymphoma in general with age 60 years or older adversely affecting
      survival.

PMID- 16586498
TI  - Conditional survival of patients with diffuse large B-cell lymphoma.
AB  - BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of
      diagnosis and the estimates are guided by the International Prognostic Index
      (IPI). However, conditional survival estimates are more informative clinically,
      as they consider those patients only who have already survived a period of time
      after treatment. Conditional survival data have not been reported for lymphoma
      patients. METHODS: Conditional survival was estimated for 1209 patients with
      diffuse large B-cell lymphoma (DLBCL) from the population-based LYFO registry of
      the Danish Lymphoma Group. The Kaplan-Meier method was used to estimate
      conditional survival at 0-5 years after diagnosis. RESULTS: The probability of
      surviving 5 years increases with each year survived for the first 3 years after
      diagnosis, after which the increase is minimal. The median survival increases
      from 38 months for all patients to between 108 and 120 months, conditioned on
      survival for at least 3-5 years. The prognostic capacity of the IPI and the age
      adjusted IPI was high at diagnosis, but the significance gradually declined in
      the first years after diagnosis. Furthermore, the prognostic impact of the
      individual clinical variables of the IPI was also significant at diagnosis, but 2
      years after diagnosis only age had prognostic impact. Multivariate analysis of
      patients who survived > or = 3 years identified only age as a prognostic factor.
      CONCLUSION: For patients with DLBCL who have survived more than 1 year after
      diagnosis, the conditional survival probability provides more accurate prognostic
      information than the conventional survival rate estimated from the time of
      diagnosis.

PMID- 16586499
TI  - ACTIBIND, an actin-binding fungal T2-RNase with antiangiogenic and
      anticarcinogenic characteristics.
AB  - BACKGROUND: ACTIBIND is an Aspergillus niger extracellular ribonuclease (T2
      ribonuclease [RNase]) that possesses actin-binding activity. In plants, ACTIBIND
      inhibits the elongation and alters the orientation of pollen tubes by interfering
      with the intracellular actin network. The question rose whether ACTIBIND can also
      affect mammalian cancer development. METHODS: Cell colony formation was performed
      in human colon (HT-29, Caco-2, RSB), breast (ZR-75-1), and ovarian (2780) cancer
      cells in the presence or absence of 1 muM ACTIBIND. In HT-29 and ZR-75-1 cells,
      the effect of ACTIBIND on cell migration was studied by microscopic observations
      and by invasion assay through Matrigel. Tube formation was assessed in human
      umbilical vein endothelial cells (HUVEC) in the presence of angiogenin or basic
      fibroblast growth factor (bFGF) (1 microg/mL each) following overnight incubation
      with 1 or 10 microM ACTIBIND. In an athymic mouse xenograft model, HT-29 cells
      were injected subcutaneously, followed by subcutaneous (0.4-8 mg/mouse/injection)
      or intraperitoneal (0.001-1 mg/mouse/injection) injections of ACTIBIND. In a rat
      dimethylhydrazine (DMH)-colorectal carcinogenesis model, ACTIBIND was released
      directly into the colon via osmotic micropumps (250 microg/rat/day) or given
      orally via microcapsules (1.6 mg/rat/day). Aberrant crypt foci, tumors in the
      distal colon, and tumor blood vessels were examined. RESULTS: ACTIBIND had an
      anticlonogenic effect unrelated to its ribonuclease activity. It also inhibited
      angiogenin-induced HUVEC tube formation in a dose-responsive manner. ACTIBIND was
      found to bind actin in vitro. It also bound to cancer cell surfaces, leading to
      disruption of the internal actin network and inhibiting cell motility and
      invasiveness through Matrigel-coated filters. In mice, ACTIBIND inhibited HT-29
      xenograft tumor development, given either as a subcutaneous or intraperitoneal
      treatment. In rats, ACTIBIND exerted preventive and therapeutic effects on
      developing colonic tumors induced by DMH. It also reduced the degree of tumor
      observation. CONCLUSIONS: This study indicated that ACTIBIND is an effective
      antiangiogenic and anticarcinogenic factor.

PMID- 16586500
TI  - In vivo genotoxic effects of industrial waste leachates in mice following oral
      exposure.
AB  - Contamination of ground water by industrial waste poses potential health hazards
      for man and his environment. The improper disposal of toxic wastes could allow
      genotoxic chemicals to percolate into ground waters, and these contaminated
      ground waters may produce toxicity, including mutation and eventually cancer, in
      exposed individuals. In the present study, we evaluated the in vivo genotoxic
      potential of leachates made from three different kinds of industrial waste
      (tannery waste, metal-based waste, and waste containing dyes and pigments) that
      are disposed of in areas adjoining human habitation. Three different doses of
      test leachates were administered by oral gavage for 15 consecutive days to Swiss
      albino mice; their bone marrow cells were examined for chromosome aberrations
      (CAs), micronucleated polychromatic erythrocytes (MNPCEs), and DNA damage using
      the alkaline Comet assay. Exposure to the leachates resulted in significant (P <
      0.05 or P < 0.001) dose-dependent increases in chromosome and DNA damage.
      Fragmented chromosomes and chromatid breaks were the major CAs observed. Chemical
      analysis of the leachates indicated that chromium and nickel were elevated above
      the limits established by health organizations. The highest levels of
      genotoxicity were produced by the metal-based leachate and the tannery-waste
      leachate, while the dye-waste leachate produced weaker genotoxic responses. The
      cytogenetic abnormalities and DNA damage produced by the leachates indicate that
      humans consuming water contaminated with these materials are at increased risk of
      developing adverse health consequences.

PMID- 16586501
TI  - Surgical treatment for spinal accessory nerve injury.
AB  - We report on the surgical results of spinal accessory nerve injuries between 1992
      2003. We operated on 10 patients (9 female, and 1 male) who had injuries of the
      spinal accessory nerve. All injuries were iatrogenic. The mean age of patients
      was 39.2 years (range, 20-57 years). The average interval between date of injury
      and surgery was 7 months (range, 4-12 months). All patients had stiffness and
      pain in the shoulder girdle. The average active abduction of the shoulder joint
      was 79.5 degrees (range, 60-100 degrees ) before surgery. End-to-end repairs were
      performed in 7 cases, and graft repairs were indicated in 3 cases. The mean
      follow-up period was 18.4 months (range, 8-36 months). The average active
      abduction of the shoulder joint was 171 degrees (range, 140-180 degrees ) at time
      of final follow-up.

PMID- 16586502
TI  - Concepts of nerve regeneration and repair applied to brachial plexus
      reconstruction.
AB  - Brachial plexus injury is a serious condition that usually affects young adults.
      Progress in brachial plexus repair is intimately related to peripheral nerve
      surgery, and depends on clinical and experimental studies. We review the rat
      brachial plexus as an experimental model, together with its behavioral
      evaluation. Techniques to repair nerves, such as neurolysis, nerve coaptation,
      nerve grafting, nerve transfer, fascicular transfer, direct muscle neurotization,
      and end-to-side neurorraphy, are discussed in light of the authors' experimental
      studies. Intradural repair of the brachial plexus by graft implants into the
      spinal cord and motor rootlet transfer offer new possibilities in brachial plexus
      reconstruction. The clinical experience of intradural repair is presented.
      Surgical planning in root rupture or avulsion is proposed. In total avulsion, the
      authors are in favor of the reconstruction of thoraco-brachial and abdomino
      antebrachial grasping, and on the transfer of the brachialis muscle to the wrist
      extensors if it is reinnervated. Surgical treatment of painful conditions and new
      drugs are also discussed.

PMID- 16586503
TI  - Model of the mass transport to the surface of animal cells cultured in a rotating
      bioreactor operated in micro gravity.
AB  - A mathematical model is used to investigate the transport of dissolved oxygen
      from the bulk fluid to the surface of aggregates of animal cells cultured in a
      rotating bioreactor. These aggregates move through different regions of the
      bioreactor with a local flow field and concentration distribution that vary with
      time. The time variation of the Sherwood number and the surface concentration for
      a range of parameters typical of a cell science experiment executed in the
      Rotating Wall Perfused Vessel (RWPV) bioreactor in space are investigated. The
      Reynolds numbers experienced by the aggregate are generally low (Re < 1) and the
      Peclet numbers range from O(1) to O(100). Comparison of the results from the
      numerical solution of the mathematical model with those from a quasi-steady
      model, using a steady-state correlation for mass transport on a sphere, indicate
      that the quasi-steady assumption is not a good model to compute the instantaneous
      Sherwood number. This indicates a significant history effect in the Sherwood
      number response to the variations of acceleration of the aggregates in the
      bioreactor. A high resistance to the mass transport from the bulk fluid to the
      surface of the aggregate exists for the bioreactor operated in micro gravity. The
      difference between the surface concentration and the free stream concentration
      was as high as 30% for aggregates larger than 3 mm. Diffusion reduces the
      variations of the free stream concentration resulting in a nearly constant value
      for the concentration at the surface of the aggregates.

PMID- 16586504
TI  - Model-based analysis and design of a microchannel reactor for tissue engineering.
AB  - Recently developed perfusion micro-bioreactors offer the promise of more
      physiologic in vitro systems for tissue engineering. Successful application of
      such bioreactors will require a method to characterize the bioreactor environment
      required to elicit desired cell function. We present a mathematical model to
      describe nutrient/growth factor transport and cell growth inside a microchannel
      bioreactor. Using the model, we first show that the nature of spatial gradients
      in nutrient concentration can be controlled by both design and operating
      conditions and are a strong function of cell uptake rates. Next, we extend our
      model to investigate the spatial distributions of cell-secreted soluble
      autocrine/paracrine growth factors in the bioreactor. We show that the convective
      transport associated with the continuous cell culture and possible media
      recirculation can significantly alter the concentration distribution of the
      soluble signaling molecules as compared to static culture experiments and hence
      needs special attention when adapting static culture protocols for the
      bioreactor. Further, using an unsteady state model, we find that spatial
      gradients in nutrient/growth factor concentrations can bring about spatial
      variations in the cell density distribution inside the bioreactor, which can
      result in lowered working volume of the bioreactor. Finally, we show that the
      nutrient and spatial limitations can dramatically affect the composition of a co
      cultured cell population. Our results are significant for the development,
      design, and optimization of novel micro-channel systems for tissue engineering.

PMID- 16586505
TI  - Engineering of protein thermodynamic, kinetic, and colloidal stability: Chemical
      Glycosylation with monofunctionally activated glycans.
AB  - In this work we establish the relationship between chemical glycosylation and
      protein thermodynamic, kinetic, and colloidal stability. While there have been
      reports in the literature that chemical glycosylation modulates protein
      stability, mechanistic details still remain uncertain. To address this issue, we
      designed and coupled monofunctional activated glycans (lactose and dextran) to
      the model protein alpha-chymotrypsin (alpha-CT). This resulted in a series of
      glycoconjugates with variations in the glycan size and degree of glycosylation.
      Thermodynamic unfolding, thermal inactivation, and temperature-induced
      aggregation experiments revealed that chemical glycosylation increased protein
      thermodynamic (Delta G(25 degrees C)), kinetic (t(1/2)(45 degrees C)), and
      colloidal stability. These results highlight the potential of chemical
      glycosylation with monofunctional activated glycans as a technology for
      increasing the long-term stability of liquid protein formulations for industrial
      and biotherapeutic applications.

PMID- 16586506
TI  - Responses of defense signals, biosynthetic gene transcription and taxoid
      biosynthesis to elicitation by a novel synthetic jasmonate in cell cultures of
      Taxus chinensis.
AB  - Recently novel synthetic jasmonate derivatives were shown to have very powerful
      stimulating effects on the biosynthesis of taxuyunnanine C (Tc) by Taxus
      chinensis cells (Biotech Bioeng, 86:595; ibid. 86: 809, 2004). To provide an
      insight into the elicitation mechanism of the newly synthesized elicitors, by
      taking 2-hydroxyethyl jasmonate (HEJ, at 100 microM) as a typical example, in
      this work the defense signals were detected and their influences on the
      expression of important genes in taxoid biosynthetic pathway were examined in
      cell cultures of T. chinensis. The oxidative burst (induced H2O2 production) was
      confirmed, and the induction of lipoxygenase (LOX) activity and intracellular
      jasmonate acid (JA) synthesis was found. The gene transcription of geranylgeranyl
      diphosphate synthase (GGPPs) and taxa-4(5),11(12)-diene synthase (TS) was up
      regulated by HEJ elicitation compared to control. Inhibition of JA biosynthesis
      by a putative LOX inhibitor, ibuprofen (IBU), effectively depressed the HEJ
      induced up-regulation of GGPPs and TS gene transcription levels. In contrast, the
      inhibition of H2O2 production by membrane NADPH oxidase inhibitor, diphenylene
      iodonium (DPI), did not affect the transcriptions of those genes. For the HEJ
      induced Tc production, it was suppressed with addition of DPI or IBU. The results
      suggest that both H2O2 and JA signals were involved in HEJ-induced Tc
      biosynthesis, and JA mediated the induction of GGPPs and TS genes expression, but
      H2O2 was not essential to activate them. Finally, a signal transduction cascade
      from defense signal response to activated transcription of taxoid biosynthetic
      genes and enhanced Tc production is proposed.

PMID- 16586507
TI  - Effect of the plant peptide regulator, phytosulfokine-alpha, on the growth and
      Taxol production from Taxus sp. suspension cultures.
AB  - Phytosulfokine-alpha (PSK-alpha) is a small plant peptide (5 amino acids) that
      displays characteristics typically associated with animal peptide hormones. PSK
      alpha was originally isolated based on its mitogenic activity with plant
      cultures; it has been reported to increase production of tropane alkaloids from
      Atropa belladonna, although its general influence on secondary metabolite
      production is unknown. The studies reported in this article were initiated to
      evaluate the effects of PSK-alpha supplementation on production of Taxol
      (paclitaxel) from plant cell cultures of Taxus sp. particularly when methyl
      jasmonate (MeJA) is added as an elicitor of secondary metabolism. The response to
      PSK-alpha supplementation was cell line dependent. Taxus cuspidata P93AF showed
      no statistically significant response to PSK-alpha supplementation while Taxus
      canadensis C93AD and T. cuspidata PO93X displayed a concentration-dependent
      response (up to 100 nM PSK-alpha added in first 24 h of culture) with a decrease
      in initial growth rate, an increase in cell density (dry weight/fresh weight),
      and increased Taxol production. More remarkably with T. canadensis (C93AD), a
      very strong synergistic response of PSK-alpha (100 nM) and methyl jasmonate
      (MeJA, 100 microM) elicitation was observed, resulting in Taxol level of 35.3 +/-
      2.1 mg/L or 1.83 +/- 0.02 mg Taxol/g dry cell weight achieved at day 21, a level
      of approximately 10-fold higher than for either treatment by itself. Although the
      level of Taxol production achieved is not remarkable, this synergistic treatment
      was able to partially revive taxane production in cultures that have lost
      productivity due to extended time (over 10 years) in continuous subculture.

PMID- 16586509
TI  - Analysis of cell growth and diffusion in a scaffold for cartilage tissue
      engineering.
AB  - Developments in tissue engineering over the past decade have offered promising
      future for the repair and reconstruction of damaged tissues. To regenerate three
      dimensional and weight-bearing implants, advances in biomaterials and
      manufacturing technologies prompted cell cultivations with natural or artificial
      scaffolds, in which cells are allowed to proliferate, migrate, and differentiate
      in vitro. In this article, we develop a mathematical model for cell growth in a
      porous scaffold. By treating the cell-scaffold construct as a porous medium, a
      continuum model is set up based on basic principles of mass conservation. In
      addition to cell growth kinetics, we incorporate cell diffusion in the model to
      describe the effects of cell random walks. Computational results are compared to
      experimental data found in the literature. With this model, we are able to
      investigate cell motility, heterogeneous cell distributions, and non-uniform
      seeding for tissue engineering applications. Results show that random walks tend
      to enhance uniform cell spreads in space, which in turn increases the
      probabilities for cells to acquire nutrients; therefore random walks are likely
      to be a positive contribution to the overall cell growth on scaffolds.

PMID- 16586508
TI  - Impact of long-term partial aeration on the removal of 2,4,6-trichlorophenol in
      an initially methanogenic fluidized bed bioreactor.
AB  - A fluidized bed bioreactor (FBBR) was operated for more than 1000 days under two
      regimes, Methanogenic (M) and Methanogenic-Aerobic (M-A), to remove 2,4,6
      trichlorophenol (TCP) and phenol (Phe) from a synthetic wastewater, containing
      different amounts of TCP and Phe, using different aeration flow-rates (0, 2.13,
      and 1.06 NL O(2)/L.day). M conditions (80:20 mg/L of TCP:Phe, 0 NL O(2)/L.day)
      showed similar TCP and Phe removal (>95%). Nevertheless accumulation of 4
      chlorophenol (4CP) up to 16 mg/L and Phe up to 4 mg/L was observed, while in M-A
      conditions (80:20 mg/L of TCP:Phe, 2.13 NL O(2)/L.day) TCP and Phe removal
      achieved 99.9(+)% and after 70 days no accumulation of intermediates were
      detected. The increase of TCP and Phe in the influent under M-A conditions from
      80:20 to 120:30 mg/L of TCP:Phe did not negatively affect the removal of TCP,
      intermediates and Phe; in fact, they were similar to those in previous M-A
      conditions. The decrease in the oxygen flow rate from 2.13 to 1.06 NL O(2)/L.day
      had no negative effect on pollutant removals, which were as high as in previous
      two M-A conditions. The specific methanogenic activity of bioparticles of the
      fluidized bed decreased with long-term partial aeration, starting from 1.097 mmol
      CH(4)/h.g(TKN) in the M regime (day 60) to <0.02 mmolCH(4)/h.g(TKN) at day 1050,
      suggesting aerobic regime in the bioreactor rather than an M-A regime. In
      conclusion, complete removal of TCP and less chlorinated intermediates could be
      achieved in an initially methanogenic FBBR under conditions of partial aeration,
      although long-term operation seemed to negatively affect the methanogenic
      activity of biomass. It is also likely that after extended aeration the microbial
      community was finally enriched with strains with the ability to attack 2,4,6-TCP
      under aerobic conditions. This report represents the first evidence of a long
      exposure to oxygen of an anaerobic microbial consortium that efficiently remove
      TCP.

PMID- 16586511
TI  - Expression of viral capsid protein antigen against Epstein-Barr virus in plastids
      of Nicotiana tabacum cv. SR1.
AB  - Epstein-Barr virus (EBV) infects nearly 90% of adults worldwide and is the
      pathogenic source of a broad spectrum of malignancies originating from lymphoid
      and epithelial cells. Currently, no vaccine has been developed to immunologically
      inactivate this virus. In infected patients, anti-EBV viral capsid antigen (VCA)
      immunoglobins represent some of the useful diagnostic markers for carcinoma
      development. To demonstrate that the EBV VCA antigen can be produced in plants,
      the plastid genome of tobacco (Nicotiana tabacum cv. SR1) was transformed with a
      VCA-expressing cassette. The EBV VCA mRNA was actively transcribed in the
      transplastomic plants and antigen production was detected. This study indicates
      that plastid transformation could be a promising strategy in EBV VCA antigen
      production.

PMID- 16586510
TI  - Siderophore production by using free and immobilized cells of two pseudomonads
      cultivated in a medium enriched with Fe and/or toxic metals (Cr, Hg, Pb).
AB  - Pseudomonads are serious candidates for siderophore production applied to toxic
      metal (TM) solubilization. The bioaugmentation of contaminated soils by these TM
      solubilizing bacteria combined with phytoextraction is an emerging clean-up
      technology. Unfortunately, siderophore synthesis may be drastically reduced by
      soluble iron in soils and bacteria can suffer from TM toxicity. In this study, we
      compared siderophore production by Pseudomonas aeruginosa and Pseudomonas
      fluorescens by using free and immobilized cells in Ca-alginate beads incubated in
      a medium containing Fe and/or TM (mixture of Cr, Hg, and Pb in concentrations
      which represented the soluble fraction of a contaminated agricultural soil). Free
      cell growth was stimulated by Fe, whatever the microorganism, the inoculum size
      and the presence or not of TM might have been. P. aeruginosa was less sensitive
      to TM than P. fluorescens. By comparison with free cells, immobilization with the
      high inoculum size showed less sensitivity to TM most probably because of lower
      metal diffusion in beads. Indeed, a maximum of 99.1% of Cr, 57.4% of Hg, and
      99.6% of Pb were adsorbed onto beads. The addition of iron in the culture medium
      reduced significantly siderophore production of free cells while it led only to a
      low decrease with their immobilized counterparts, in particular with P.
      aeruginosa. In culture medium enriched with Fe and/or TM, siderophore-specific
      production of immobilized cells was higher than for free cells.

PMID- 16586512
TI  - Assaying CO2 release for determination of formate dehydrogenase activity in
      entrapment matrices and aqueous-organic two-phase systems.
AB  - Formate dehydrogenase is an important enzyme for NADH-regeneration in enzyme
      catalysed reductions. Methods to determine the activity of this biocatalyst
      during reaction in aqueous-organic two-phase systems or after immobilisation were
      therefore investigated. Determination of gaseous CO2 in the headspace of reaction
      vessels either by gas chromatography or by pressure sensors was found to be a
      suitable way for deduction of FDH-activity in either of these reaction systems.
      In the presence of organic solvents, gas chromatography yielded more precise data
      than pressure sensors, while pressure measurements offer the opportunity to assay
      continuously the activity of entrapped FDH throughout the whole course of
      reaction.

PMID- 16586515
TI  - Percutaneous replacement of pulmonary valve using the Edwards-Cribier
      percutaneous heart valve: first report in a human patient.
AB  - We report on the use of the Edwards-Cribier percutaneous heart valve (PHV) in a
      stenotic right ventricle to pulmonary artery homograft in a 16-year old patient
      who underwent the Ross operation. Initially, the homograft was stented and at the
      same procedure, the PHV was deployed inside it. This is the first human case of
      the application of this valve in the pulmonary valve position.

PMID- 16586516
TI  - Taking a bite out of the femoral artery: vascular closure and vascular
      obstruction.

PMID- 16586518
TI  - Functionalized chiral ionic liquids as highly efficient asymmetric
      organocatalysts for Michael addition to nitroolefins.

PMID- 16586519
TI  - Broadband femtosecond fluorescence spectroscopy of [Ru(bpy)3]2+.

PMID- 16586517
TI  - Claudication secondary to Perclose use after percutaneous procedures.
AB  - The use of suture-mediated arterial closure devices has dramatically increased
      with the increased number of percutaneous procedures being performed.
      Complications from suture-mediated closure devices have been underreported.
      Specifically, arterial stenosis resulting in claudication has not been previously
      described in detail. We present nine patients who presented with various leg
      symptoms after Perclose was used to achieve arterial hemostasis following
      percutaneous procedures. All cases were found to have significant arterial
      stenoses from the Perclose sutures. Once diagnosis was correctly made, the
      patients either underwent surgical repair or percutaneous balloon angioplasty and
      in all cases the symptoms abated.

PMID- 16586520
TI  - A bis(pyridyl)allenylidene complex of ruthenium: a "molecular clip" that displays
      intense near-infrared absorption upon coordination to a ruthenium(II) center.

PMID- 16586522
TI  - Dynamic combinatorial chemistry: the unexpected choice of receptors by guest
      molecules.

PMID- 16586521
TI  - Confined synthesis of a cis-isotactic ladder polysilsesquioxane by using a pi
      stacking and H-bonding superstructure.

PMID- 16586523
TI  - Microwave-assisted Suzuki coupling reactions with an encapsulated palladium
      catalyst for batch and continuous-flow transformations.
AB  - This article describes the design, optimisation and development of a Suzuki cross
      coupling protocol mediated by an efficient palladium-encapsulated catalyst (Pd
      EnCat) under microwave irradiation. The methodology has been used in both batch
      mode for classical library preparation and in continuous-flow applications
      furnishing multigram quantities of material. Described is a method that uses
      direct focused microwave heating whilst applying an external cooling source. This
      enables a lower than normal bulk temperature to be maintained throughout the
      reaction period leading to significant improvements in the overall yield and
      purity of the reaction products. Additional aspects of this novel heating
      protocol are discussed in relation to the prolonged lifetime and enhanced
      reactivity of the immobilised catalyst system.

PMID- 16586524
TI  - In search of ionic liquids incorporating azolate anions.
AB  - Twenty-eight novel salts with tetramethyl-, tetraethyl-, and tetrabutylammonium
      and 1-butyl-3-methylimidazolium cations paired with 3,5-dinitro-1,2,4-triazolate,
      4-nitro-1,2,3-triazolate, 2,4-dinitroimidazolate, 4,5-dinitroimidazolate, 4,5
      dicyanoimidazolate, 4-nitroimidazolate, and tetrazolate anions have been prepared
      and characterized by using differential scanning calorimetry (DSC),
      thermogravimetric analysis (TGA), and single-crystal X-ray crystallography. The
      effects of cation and anion type and structure on the physicochemical properties
      of the resulting salts, including several ionic liquids, have been examined and
      discussed. Ionic liquids (defined as having m.p.<100 degrees C) were obtained
      with all combinations of the 1-butyl-3-methylimidazolium cation ([C(4)mim](+))
      and the heterocyclic azolate anions studied, and with several combinations of
      tetraethyl or tetrabutylammonium cations and the azolate anions. The [C(4)mim](+)
      azolates were liquid at room temperature exhibiting large liquid ranges and
      forming glasses on cooling with glass-transition temperatures in the range of -53
      to -82 degrees C (except for the 3,5-dinitro-1,2,4-triazolate salt with m.p. 33
      degrees C). Six crystal structures of the corresponding tetraalkylammonium salts
      were determined and the effects of changes to the cations and anions on the
      packing of the structure have been investigated.

PMID- 16586525
TI  - pK(a) Switching induced by the change in the pi-conjugated system based on
      photochromism.
AB  - Two diarylethene derivatives 1 a and 2 a containing a 2,5-diaryl-3-thienyl group
      have been designed and synthesized. The pK(a) values of these compounds change
      upon photoirradiation. They have a phenol group as a proton source and a
      pyridinium group as an acceptor unit at each end of the pi-conjugated chain. The
      cyclization/cycloreversion reactions can be used to control the length of the pi
      conjugated chain between the proton source and the acceptor. The change in the pi
      conjugated chain length caused the pK(a)-switching.

PMID- 16586526
TI  - Quantification of ultrasound-induced chain scission in PdII-phosphine
      coordination polymers.
AB  - A kinetically inert, reversible coordination polymer (3) was obtained through
      complexation of dicyclohexylphosphine telechelic poly(tetrahydrofuran) with
      palladium(II) dichloride. This coordination polymer is unreactive towards
      palladium(II) dichloride bis(1-diphenylphosphino)dodecane (4), because ligand
      dissociation in the coordination polymer is slow. However, upon ultrasonication
      of solutions of 3 in toluene in the presence of 4, formation of palladium(II)
      heterocomplexes was observed with (31)P NMR spectroscopy. Heterocomplex
      formation, the consumption of 4, and changes in molecular weight were used to
      quantify the scission process. In the presence of 60 equivalents of the
      alkyldiphenylphosphine stopper complex, the reduction in molecular weight was
      strongly enhanced; over a period of eight hours the weight-averaged molecular
      weight was reduced from 1.1x10(5) to 2.3x10(4) g mol(-1) while 47 % of the
      palladium(II) complexes in the coordination polymer had been converted into
      heterocomplexes. These results show that the system of 3 in combination with
      scavenger 4 is a suitable system to study the efficiency of ultrasound-induced
      chain scission of coordination polymers.

PMID- 16586527
TI  - Rationally designed chemical modulators convert a bacterial channel protein into
      a pH-sensory valve.

PMID- 16586528
TI  - On the joint time-frequency characteristics of chemical oscillations.
AB  - A method of time-frequency transformations of nonstationary signals has been
      discussed and applied to the analysis of oscillatory Belousov-Zhabotinsky (BZ)
      reaction. Selected registers of BZ reactions, that represent regular and complex
      dynamic behavior, have been submitted to the detailed spectral analysis using the
      short time Fourier transform (STFT). It has been demonstrated that the STFT is an
      accurate and suitable method for decomposition of chemical oscillations in the
      joint time and frequency domain. The energy distribution via STFT, presented in
      this article, revealed some specific characteristics of transitions between
      different regimes in the closed system of BZ reaction.

PMID- 16586529
TI  - Rapidly convergent procedure to solve the density profile equation in the
      classical density functional theory.
AB  - An efficient recursive procedure to solve the density profile equation in the
      classical density functional theory (DFT) using an inverse Broyden method is
      described. The present iterative procedure is free of calculation of the Jacobian
      matrix, and its inversion unavoidable for the well-known Newton-Raphson (NR)
      method and its variants. Numerical calculation indicates that only the
      approximate solution and iterative matrix of the lower bulk density case are
      employed as the corresponding initial guesses of the higher bulk density case,
      the present recursive procedure can converge quickly to the physical solution
      with an accuracy of epsilon = 10(-14); therefore, the procedure provides an
      efficient numerical algorithm for the theory in which acquirement of a density
      profile of high accuracy is a key step. Extensive numerical calculation shows the
      advantage of the present inverse Broyden method over Broyles' mixing procedure
      and a modified Powell hybrid algorithm (a variation of the NR method).

PMID- 16586530
TI  - Intra- and intermolecular interactions between cyclic-AMP receptor protein and
      DNA: ab initio fragment molecular orbital study.
AB  - The ab initio fragment molecular orbital (FMO) calculations were performed for
      the cAMP receptor protein (CRP) complexed with a cAMP and DNA duplex to elucidate
      their sequence-specific binding and the stability of the DNA duplex, as
      determined by analysis of their inter- and intramolecular interactions.
      Calculations were performed with the AMBER94 force field and at the HF and MP2
      levels with several basis sets. The interfragment interaction energies (IFIEs)
      were analyzed for interactions of CRP-cAMP with each base pair, DNA duplex with
      each amino acid residue, and each base pair with each residue. In addition, base
      base interactions were analyzed including hydrogen bonding and stacking of DNA.
      In the interaction between DNA and CRP-cAMP, there was a significant charge
      transfer (CT) from the DNA to CRP, and this CT interaction played an important
      role as well as the electrostatic interactions. It is necessary to apply a
      quantum mechanical approach beyond the "classical" force-field approach to
      describe the sequence specificity. In the DNA intramolecular interaction, the
      dispersion interactions dominated the stabilization of the base-pair stacking
      interactions. Strong, attractive 1,2-stacking interactions and weak, repulsive
      1,3-stacking interactions were observed. Comparison of the intramolecular
      interactions of free and complexed DNA revealed that the base-pairing
      interactions were stronger, and the stacking interactions were weaker, in the
      complexed structure. Therefore, the DNA duplex stability appears to change due to
      both the electrostatic and the CT interactions that take place under conditions
      of DNA-CRP binding.

PMID- 16586531
TI  - Determination of the DeltapKa between the active site cysteines of thioredoxin
      and DsbA.
AB  - Thioredoxin superfamily members share a considerable degree of structural
      similarity, with a conserved CX(i)X(j)C motif at the active site, where C stand
      for two cysteines that alternate between a reduced thiol and oxidized disulfide
      states, and X(i)and X(j) are two amino acids different in each family member.
      Despite these similarities, they display very different redox potentials and pKas
      for the active site dithiol, and fulfill different physiological roles.
      Thioredoxin, for example, promotes the reduction of disulfide bonds, while DsbA
      promotes their oxidation in prokaryotic cells. The factors that promote these
      differences are still not fully understood. However, it is generally accepted
      that the different stabilities of the redox active disulfide bond depends on the
      degree of stabilization, in the reduced state, of the thiolate of one of the
      active site cysteines (nucleophilic cysteine). In this work we have used QM/MM
      methods to compare and characterize the active site dithiols of both enzymes, and
      to shed some light on the structural features responsible for the large
      differences in pKa and redox potential between two homologous enzymes,
      thioredoxin and DsbA. We have also analyzed the main factors pointed out in the
      literature as responsible for their different properties. We obtained the value
      of 4.5 for pKa difference (DeltapKa) between the nucleophilic cysteines of both
      enzymes, which is in excellent agreement with most of the experimental values.
      Additionally, we found that the principal differentiating factor responsible for
      this observed DeltapKa are the alpha2-alpha helices, which greatly contribute to
      the mentioned value, by stabilizing the DsbA thiolate in a much greater extend
      than the thioredoxin thiolate. A double mutation of the conserved residues Asp26
      and Lys57, in thioredoxin, and Glu24 Lys58, in DsbA, by alanines did not change
      the DeltapKa value; this supports the hypothesis that these residues are not
      involved in the differentiation of the properties of the active centre dithiol.
      However, we found out that these residues are important for the stabilization of
      the nucleophilic thiolate. The X(i) and X(j) residues also do not seem to promote
      the stabilization of the thiolates. In fact, the corresponding double alanine
      mutants are more stable than the wild-type enzymes. However, these residues are
      involved in the differentiation between thioredoxin and DsbA, stabilizing the
      DsbA thiolate by a larger extent than the thioredoxin thiolate.

PMID- 16586532
TI  - Intestinal sugar transport.
AB  - Carbohydrates are an important component of the diet. The carbohydrates that we
      ingest range from simple monosaccharides (glucose, fructose and galactose) to
      disaccharides (lactose, sucrose) to complex polysaccharides. Most carbohydrates
      are digested by salivary and pancreatic amylases, and are further broken down
      into monosaccharides by enzymes in the brush border membrane (BBM) of
      enterocytes. For example, lactase-phloridzin hydrolase and sucrase-isomaltase are
      two disaccharidases involved in the hydrolysis of nutritionally important
      disaccharides. Once monosaccharides are presented to the BBM, mature enterocytes
      expressing nutrient transporters transport the sugars into the enterocytes. This
      paper reviews the early studies that contributed to the development of a working
      model of intestinal sugar transport, and details the recent advances made in
      understanding the process by which sugars are absorbed in the intestine.

PMID- 16586534
TI  - Interleukin-10 and chronic liver disease.
AB  - Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many
      cell populations. Numerous investigations suggest that IL-10 plays a major role
      in chronic liver diseases. IL-10 gene polymorphisms are possibly associated with
      liver disease susceptibility or severity. Recombinant human IL-10 has been
      produced and is currently tested in clinical trials. These trials may give new
      insights into the immunobiology of IL-10 and suggest that the IL-10/IL-10
      receptor system may become a new therapeutic target.

PMID- 16586533
TI  - Helicobacter pylori eradication to prevent gastric cancer: underlying molecular
      and cellular mechanisms.
AB  - Numerous cellular and molecular events have been described in development of
      gastric cancer. In this article, we overviewed roles of Helicobacter pylori (H
      pylori) infection on some of the important events in gastric carcinogenesis and
      discussed whether these cellular and molecular events are reversible after cure
      of the infection. There are several bacterial components affecting gastric
      epithelial kinetics and promotion of gastric carcinogenesis. The bacterium also
      increases risks of genetic instability and mutations due to NO and other reactive
      oxygen species. Epigenetic silencing of tumor suppressor genes such as RUNX3 may
      alter the frequency of phenotype change of gastric glands to those with
      intestinal metaplasia. Host factors such as increased expression of growth
      factors, cytokines and COX-2 have been also reported in non-cancerous tissue in H
      pylori-positive subjects. It is noteworthy that most of the above phenomena are
      reversed after the cure of the infection. However, some of them including
      overexpression of COX-2 continue to exist and may increase risks for
      carcinogenesis in metaplastic or dysplastic mucosa even after successful H pylori
      eradication. Thus, H pylori eradication may not completely abolish the risk for
      gastric carcinogenesis. Efficiency of the cure of the infection in suppressing
      gastric cancer depends on the timing and the target population, and warrant
      further investigation.

PMID- 16586535
TI  - Association of smoking, alcohol drinking and dietary factors with esophageal
      cancer in high- and low-risk areas of Jiangsu Province, China.
AB  - AIM: To study the main environmental and lifestyle factors that account for the
      regional differences in esophageal cancer (EC) risk in low- and high-risk areas
      of Jiangsu Province, China. METHODS: Since 2003, a population-based case-control
      study has been conducted simultaneously in low-risk (Ganyu County) and high-risk
      (Dafeng County) areas of Jiangsu Province, China. Using identical protocols and
      pre-tested standardized questionnaire, following written informed consent,
      eligible subjects were inquired about their detail information on potential
      determinants of EC, including demographic information, socio-economic status,
      living conditions, disease history, family cancer history, smoking, alcohol
      drinking, dietary habits, frequency, amount of food intake, etc. Conditional
      logistic regression with maximum likelihood estimation was used to obtain Odds
      ratio (OR) and 95 % confidence interval (95% CI), after adjustment for potential
      confounders. RESULTS: In the preliminary analysis of the ongoing study, we
      recruited 291 pairs of cases and controls in Dafeng and 240 pairs of cases and
      controls in Ganyu, respectively. In both low-risk and high-risk areas, EC was
      inversely associated with socio-economic status, such as level of education, past
      economic status and body mass index. However, this disease was more frequent
      among those who had a family history of cancer or encountered misfortune in the
      past 10 years. EC was also more frequent among smokers, alcohol drinkers and fast
      eaters. Furthermore, there was a geographic variation of the associations between
      smoking, alcohol drinking and EC risk despite the similar prevalence of these
      risk factors in both low-risk and high-risk areas. The dose-response relationship
      of smoking and smoking related variables, such as age of the first smoking,
      duration and amount were apparent only in high-risk areas. On the contrary, a
      dose-response relationship on the effect of alcohol drinking on EC was observed
      only in low-risk areas. CONCLUSION: The environmental risk factors, together with
      genetic factors and gene-environmental interactions might be the main reason for
      this high-risk gradient in Jiangsu Province, China.

PMID- 16586536
TI  - Effects of tachyplesin and n-sodium butyrate on proliferation and gene expression
      of human gastric adenocarcinoma cell line BGC-823.
AB  - AIM: To investigate the effects of tachyplesin and n-sodium butyrate on
      proliferation and gene expression of human gastric adenocarcinoma cell line BGC
      823. METHODS: Effects of tachyplesin and n-sodium butyrate on proliferation of
      BGC-823 cells were determined with trypan blue dye exclusion test and HE
      staining. Effects of tachyplesin and n-sodium butyrate on cell cycle were
      detected by flow cytometry. Protein levels of c-erbB-2, c-myc, p53 and p16 were
      examined by immunocytochemistry. RESULTS: The inhibiting effects were similar
      after 2.0 mg/L tachyplesin and 2.0 mmol/L n-sodium butyrate treatment, the
      inhibitory rate of cellular growth was 62.66% and 60.19% respectively, and the
      respective maximum mitotic index was decreased by 49.35% and 51.69% respectively.
      Tachyplesin and n-sodium butyrate treatment could markedly increase the
      proportion of cells at G(0)/G(1) phase and decrease the proportion at S phase.
      The expression levels of oncogene c-erbB-2, c-myc, and mtp53 proteins were down
      regulated while the expression level of tumor suppressor gene p16 protein was up
      regulated after the treatment with tachyplesin or n-sodium butyrate. The effects
      of 1.0 mg/L tachyplesin in combination with 1.0 mmol/L n-sodium butyrate were
      obviously superior to their individual treatment in changing cell cycle
      distribution and expression of c-erbB-2, c-myc, mtp53 and p16 protein. The
      inhibitory rate of cellular growth of BGC-823 cells after combination treatment
      was 62.29% and the maximum mitotic index was decreased by 51.95%. CONCLUSION:
      Tachyplesin as a differentiation inducer of tumor cells has similar effects as n
      sodium butyrate on proliferation of tumor cells, expression of correlative
      oncogene and tumor suppressor gene. It also has a synergistic effect on
      differentiation of tumor cells.

PMID- 16586537
TI  - Assessment of metastatic liver disease in patients with primary extrahepatic
      tumors by contrast-enhanced sonography versus CT and MRI.
AB  - AIM: To evaluate contrast-enhanced ultrasonography (CEUS) using SonoVue in the
      detection of liver metastases in patients with known extrahepatic primary tumors
      versus the combined gold standard comprising CT, MRI and clinical/histological
      data. METHODS: It is an international multicenter study, and there were 12
      centres and 125 patients (64 males, 61 females, aged 59+/-11 years) involved,
      with 102 patients per protocol. Primary tumors were colorectal in 35%, breast in
      27%, pancreatic in 17% and others in 21%. CEUS using SonoVue was employed with a
      low-mechanical-index technique and contrast-specific software using Siemens
      Elegra, Philips HDI 5000 and Acuson Sequoia; continuous scanning for at least
      five minutes. RESULTS: CEUS with SonoVue increased significantly the number of
      focal liver lesions detected versus unenhanced sonography. In 31.4% of the
      patients, more lesions were found after contrast enhancement. The total numbers
      of lesions detected were comparable with CEUS (55), triple-phase spiral CT (61)
      and MRI with a liver-specific contrast agent (53). Accuracy of detection of
      metastatic disease (i.e. at least one metastatic lesion) was significantly higher
      for CEUS (91.2%) than for unenhanced sonography (81.4%) and was similar to that
      of triple-phase spiral CT (89.2%). In 53 patients whose CEUS examination was
      negative, a follow-up examination 3-6 mo later confirmed the absence of
      metastatic lesions in 50 patients (94.4%). CONCLUSION: CEUS is proved to be
      reliable in the detection of liver metastases in patients with known extrahepatic
      primary tumors and suspected liver lesions.

PMID- 16586538
TI  - Protocol liver biopsies in long-term management of patients transplanted for
      hepatitis B-related liver disease.
AB  - AIM: To evaluate the long-term histological outcome of patients transplanted for
      HBV-related liver disease and given HBIg prophylaxis indefinitely after LT.
      METHODS: Forty-two consecutive patients transplanted for hepatitis B were
      prospectively studied. HBsAg, HBV-DNA and liver function tests were evaluated in
      the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo
      after LT and yearly thereafter. Chronic hepatitis (CH) B after LT was classified
      as minimal, mild, moderate or severe. RESULTS: HBV recurred in 7/42 (16.6%)
      patients after 6-96 mo of follow-up. A hundred and eighty-seven LB were
      evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA
      status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB
      obtained from 28 HBsAg+/HCV- recipients with no HBV recurrence after LT, all
      biopsies were completely normal in only 2 patients (7.1%), minimal/non-specific
      changes were observed in 18 (64.2%), and at least 1 biopsy showed CH in the
      remaining 8 (28.5%). Twenty-nine LB obtained from 7 patients transplanted for HBV
      HCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial
      survival was similar in patients with HBsAg+ or HBsAg- liver diseases.
      CONCLUSION: Though protocol biopsies may enable the detection of graft
      dysfunction at an early stage, the risk of progression and the clinical
      significance of these findings remains to be determined.

PMID- 16586539
TI  - Inter-observer variability in histopathological assessment of liver biopsies
      taken in a pediatric open label therapeutic program for chronic HBV infection
      treatment.
AB  - AIM: To our knowledge, the inter-observer variability of the liver biopsy
      findings in HBV-infected children have not been studied as yet. Hence, we aimed
      to compare different pathologist's assessment of grading and staging in liver
      biopsies obtained from children prior to interferon treatment. METHODS: We
      collected 920 biopsies from 11 medical centers. The biopsies were independently
      reviewed by 6 pathologists from academic centers who assessed Batts-Ludwig score
      for grading and staging. Satisfactory agreement among observers was defined as at
      least 60% of observers having the same opinion. Satisfactory dispersion between
      maximal and minimal score for the same biopsy specimen was defined as a maximum 1
      point. RESULTS: Satisfactory inter-observer agreement for grading was obtained in
      51.6% and for staging in 75.7% of biopsies. Satisfactory dispersion for grading
      scores was observed in 44.5% and for staging in 72.7% of cases. CONCLUSION: Our
      study demonstrates that: (1) pathologists differ in their assessment of grading
      and staging of liver biopsies; (2) inter-observer variability for staging is
      lower than that for grading; and (3) regardless of the inter-observer variability
      of assessments, the majority of children with chronic HBV infection have mild to
      moderate inflammation and mild to moderate fibrosis.

PMID- 16586540
TI  - Effects of betaine on ethanol-stimulated secretion of IGF-I and IGFBP-1 in rat
      primary hepatocytes: involvement of p42/44 MAPK activation.
AB  - AIM: To evaluate the effects of betaine on the ethanol-induced secretion of IGF-I
      and IGFBP-1 using radioimmunoassay and Western blotting, respectively, in primary
      cultured rat hepatocytes. METHODS: Hepatocytes isolated from male Sprague-Dawley
      rats were incubated with various concentrations of ethanol and PD98059
      procedures. The hepatocytes were also treated with different doses of betaine
      (10(-5), 10(-4), and 10(-3) mol/L). We measured IGF-I and IGFBP-1 using
      radioimmunoassay and Western blotting, respectively. RESULTS: The ethanol-induced
      inhibition of IGF-I secretion was attenuated by betaine in a concentration
      dependent manner in primary cultured rat hepatocytes. At 10(-3) mol/L, betaine
      significantly increased IGF-I secretion but decreased IGFBP-1 secretion. In
      addition, p42/44 mitogen-activated protein kinase (MAPK) activity was accelerated
      significantly from 10 min to 5 h after treatment with 10(-3) mol/L betaine.
      Furthermore, the changes in IGF-1 and IGFBP-1 secretion resulting from the
      increased betaine-induced p42/44 MAPK activity in primary cultured rat
      hepatocytes was blocked by treatment with the MAPK inhibitor PD98059. Betaine
      treatment blocked the ethanol-induced inhibition of IGF-I secretion and p42/44
      MAPK activity, and the ethanol-induced increase in IGFBP-1 secretion. CONCLUSION:
      Betaine modulates the secretion of IGF-I and IGFBP-1 via the activation of p42/44
      MAPK in primary cultured rat hepatocytes. Betaine also alters the MAPK
      activations induced by ethanol.

PMID- 16586541
TI  - Cerebral processing of auditory stimuli in patients with irritable bowel
      syndrome.
AB  - AIM: To determine by brain functional magnetic resonance imaging (fMRI) whether
      cerebral processing of non-visceral stimuli is altered in irritable bowel
      syndrome (IBS) patients compared with healthy subjects. To circumvent spinal
      viscerosomatic convergence mechanisms, we used auditory stimulation, and to
      identify a possible influence of psychological factors the stimuli differed in
      their emotional quality. METHODS: In 8 IBS patients and 8 controls, fMRI
      measurements were performed using a block design of 4 auditory stimuli of
      different emotional quality (pleasant sounds of chimes, unpleasant peep (2000
      Hz), neutral words, and emotional words). A gradient echo T2*-weighted sequence
      was used for the functional scans. Statistical maps were constructed using the
      general linear model. RESULTS: To emotional auditory stimuli, IBS patients
      relative to controls responded with stronger deactivations in a greater variety
      of emotional processing regions, while the response patterns, unlike in controls,
      did not differentiate between distressing or pleasant sounds. To neutral auditory
      stimuli, by contrast, only IBS patients responded with large significant
      activations. CONCLUSION: Altered cerebral response patterns to auditory stimuli
      in emotional stimulus-processing regions suggest that altered sensory processing
      in IBS may not be specific for visceral sensation, but might reflect generalized
      changes in emotional sensitivity and affective reactivity, possibly associated
      with the psychological comorbidity often found in IBS patients.

PMID- 16586542
TI  - Effect of IBD sera on expression of inducible and endothelial nitric oxide
      synthase in human umbilical vein endothelial cells.
AB  - AIM: To study the expression of endothelial and inducible nitric oxide synthases
      (eNOS and iNOS) and their role in inflammatory bowel disease (IBD). METHODS: We
      examined the effect of sera obtained from patients with active Crohn's disease
      (CD) and ulcerative colitis (UC) on the function and viability of human umbilical
      vein endothelial cells (HUVEC). HUVECs were cultured for 0-48 h in the presence
      of a medium containing pooled serum of healthy controls, or serum from patients
      with active CD or UC. Expression of eNOS and iNOS was visualized by
      immunofluorescence, and quantified by the densitometry of Western blots.
      Proliferation activity was assessed by computerized image analyses of Ki-67
      immunoreactive cells, and also tested in the presence of the NOS inhibitor, 10(
      4) mol/L L-NAME. Apoptosis and necrosis was examined by the annexin-V-biotin
      method and by propidium iodide staining, respectively. RESULTS: In HUVEC
      immediately after exposure to UC, serum eNOS was markedly induced, reaching a
      peak at 12 h. In contrast, a decrease in eNOS was observed after incubation with
      CD sera and the eNOS level was minimal at 20 h compared to control (18%+/-16% vs
      23%+/-15% P<0.01). UC or CD serum caused a significant increase in iNOS compared
      to control (UC: 300%+/-21%; CD: 275%+/-27% vs 108%+/-14%, P<0.01).
      Apoptosis/necrosis characteristics did not differ significantly in either
      experiment. Increased proliferation activity was detected in the presence of CD
      serum or after treatment with L-NAME. Cultures showed tube-like formations after
      24 h treatment with CD serum. CONCLUSION: IBD sera evoked changes in the ratio of
      eNOS/iNOS, whereas did not influence the viability of HUVEC. These involved down
      regulation of eNOS and up-regulation of iNOS simultaneously, leading to increased
      proliferation activity and possibly a reduced anti-inflammatory protection of
      endothelial cells.

PMID- 16586544
TI  - Expression of Ets-1 proto-oncoprotein in gastrointestinal stromal tumors,
      leiomyomas and schwannomas.
AB  - AIM: Gastrointestinal stromal tumors (GISTs) are rare. GISTs differ from other
      mesenchymal tumors of the gastrointestinal tract (e.g. leiomyomas and
      schwannomas). The purpose of this study was to investigate the role of Ets-1 in
      the growth and differentiation of GISTs. METHODS: Twenty-eight GISTs, nine
      leiomyomas and six schwannomas were examined by immunohistochemical staining
      method for Ets-1 in this study. Specimens were selected from surgical pathology
      archival tissues at Nagasaki University Hospital. RESULTS: Ets-1 protein was
      expressed in the cytoplasm of cells in all of these tumors. Immunohistochemical
      staining revealed that 27 GISTs (96.4%), six leiomyomas (66.7%), and five
      schwannomas (83.3%) were positive for Ets-1. Ets-1 expression was statistically
      different between GISTs and leiomyomas (P<0.005). However, there was no
      correlation between Ets-1 expression and clinical risk categories. CONCLUSION:
      Ets-1 plays an important role in the growth and differentiation of GISTs,
      leiomyomas and schwannomas.

PMID- 16586543
TI  - Role of bile acids, prostaglandins and COX inhibitors in chronic esophagitis in a
      mouse model.
AB  - AIM: To develop a new experimental model of esophagitis that serves a
      complementary tool to clinical investigation in an insight into the mechanism of
      the damage to the esophagus mucosa by aggressive factors, and role of COX
      inhibitors in this process. METHODS: The study was conducted in 56 male mice.
      Animals were divided into seven groups: (1) perfused with HCl, (2) perfused with
      HCl and physiologic concentration of pepsin (HCl/P), (3) perfused with similar
      HCl/P solution enriched with conjugated bile acids (glycho- and tauro-sodium
      salts) designated esophageal infusion catheter under the general anesthesia, (4)
      perfused as in group 2 treated with indometacin, (5) perfused as in group 2
      treated with NS-398, (6) perfused as in group 3 treated with indometacin, and (7)
      perfused as in group 3 treated with NS-398. The esophagus was divided into 3
      parts: upper, middle and lower. The PGE2 concentration was measured in all parts
      of esophagus using RIA method. Esophagus of sacrificed animals was
      macroscopically evaluated using a low power dissecting microscope (20x).
      Specimens, representing the most frequently seen changes were fixed, stained with
      H&E and assessed microscopically using the damage score, and inflammatory score.
      RESULTS: The macroscopic changes were significantly severer in HCl/P than those
      in HCl animals (77%) and in HCl/P/BA group (43%). In HCl/P NS-398 group we
      noticed significantly less changes than those in not treated group (42%) and in
      analogical group treated with indometacin (45%). In HCl/P/BA INDO group we
      observed significantly severer changes than that in not treated group (52%). We
      noticed less changes in HCl/P NS-398 than that in group with indometacin (46%).
      In HCl/P/BA NS-398 group we had less changes than that in indometacin group
      (34%). The microscopic changes observed in HCl/P/BA INDO group were severer than
      that in not treated group (48%). Esophagitis index in HCl group was significantly
      lower than in HCl/P and also HCl/P/BA group (32% and 33%). In HCl/P/BA/INDO group
      the esophagitis surface was larger than that in not treated group (33%). In HCL/P
      group the surface of esophagus with ulceration was significantly larger (10-fold)
      than that in HCl/P/BA group. The PGE2 concentration was significantly higher in
      HCl/P group than in HCl/P/BA group. The PGE2 concentration in lower part of
      esophagus was also significantly higher in middle than those in HCl and HCl/P/BA
      groups. In upper part of esophagus the PGE2 concentration was significantly
      higher in HCl/P/BA group than that in group treated with indometacin (46%). We
      also observed higher PGE2 concentration in middle part of esophagus in HCl/P/BA
      group than those in group treated with indometacin and in group treated with
      indometacin and NS-398 (by 52% and 43% respectively). CONCLUSION: Pepsin is the
      pivotal factor in the development of chronic esophageal injury. Bile acids
      diminish chronic esophageal injury induced by HCl/P, indicating its potential
      negative impact on pepsin proteolytic potential, pivotal for mucosal injury in
      low pH. The role of selective COX inhibitors is still unclear, and needs more
      investigations. This novel chronic experimental esophagitis is an excellent model
      for further study on the role of cytokines in genetically modified animals.

PMID- 16586545
TI  - Roles of adipocyte derived hormone adiponectin and resistin in insulin resistance
      of type 2 diabetes.
AB  - AIM: To detect plasma levels of new adipocyte derived hormone adiponectin and
      resistin in type 2 diabetes patients and to explore their potential roles in
      insulin resistance in type 2 diabetes. METHODS: According to the body mass index
      (BMI), 60 type 2 diabetes patients were divided into two groups, one group was
      non-obese diabetes patients with BMI<25Kg/M(2) (30 cases) and the other group was
      obese diabetes patients with BMI>25Kg/M(2) (30 cases). There were 28 healthy
      persons in the control group. ELISA technique was employed to determine the
      plasma adiponectin and resistin concentrations. The fasting blood glucose,
      insulin and blood lipid were detected respectively by electrocheminescence
      immunoassay and immunoturbidimetric assay. Insulin resistance index and insulin
      sensitive index were calculated by the homeostasis model assessment (HOMO).
      RESULTS: The levels of plasma adiponectin were decreased significantly in
      diabetes group compared to that in control group (non-obese: 8.58+/-0.86, obese:
      6.22+/-1.34 vs 10.53+/-1.47 P<0.05); moreover, adiponectin concentration in obese
      diabetes group was significantly decreased compared to that in non-obese diabetes
      group (6.22+/-1.34 vs 8.58+/-0.86, P<0.05). The levels of plasma resistin were
      increased significantly in diabetes group compared to that in control group
      (obese: 18.64+/-4.65, non-obese: 24.05+/-9.07 vs 14.16+/-5.25, P<0.05, P<0.05);
      furthermore, the levels of resistin in obese diabetes group were increased
      significantly compared to that in non-obese diabetes group (P<0.05). Plasma
      adiponectin was correlated negatively with BMI, blood glucose, insulin resistance
      index and triglyceride (respectively, r=-0.55, P<0.01; r=-0.51, P<0.05; r=-0.52,
      P<0.05ur=-0.39, P<0.05), while it was positively correlated with insulin
      sensitive index (r=0.45, P<0.05). Conversely, plasma resistin correlated
      positively with BMI, blood glucose, triglyceride and insulin resistance index
      (respectively, r=0.40, P<0.05; r=0.52, P<0.05; r=0.46, P<0.01; r=0.27, P<0.05),
      and negatively correlated with insulin sensitive index (r=-0.32, P<0.05).
      CONCLUSION: Plasma adiponectin and resistin are associated with the disorder of
      metabolism of glucose and lipid in diabetes. The relationship between these
      hormone and insulin sensitivity suggests that they may take part in the
      development of insulin resistance of type 2 diabetes.

PMID- 16586546
TI  - Chronic hepatitis B serum promotes apoptotic damage in human renal tubular cells.
AB  - AIM: To investigate the effect of the serum of patients with chronic hepatitis B
      (CHB) on apoptosis of renal tubular epithelial cells in vitro and to study the
      role of hepatitis B virus (HBV) and transforming growth factor-beta (1) (TGF-beta
      (1)) in the pathogenesis of hepatitis B virus associated glomerulonephritis (HBV
      GN). METHODS: The levels of serum TGF-beta(1) were measured by specific enzyme
      linked immunosorbent assay (ELISA) and HBV DNA was tested by polymerase chain
      reaction (PCR) in 44 patients with CHB ,and 20 healthy persons as the control.
      The normal human kidney proximal tubular cell (HK-2) was cultured together with
      the sera of healthy persons, CHB patients with HBV-DNA negative (20 cases) and
      HBV-DNA positive (24 cases) for up to 72 h. Apoptosis and Fas expression of the
      HK-2 were detected by flow cytometer. RESULTS: The apoptosis rate and Fas
      expression of HK-2 cells were significantly higher in HBV DNA positive serum
      group 19.01%+/-5.85% and 17.58%+/-8.35%, HBV DNA negative serum group 8.12%+/
      2.80% and 6.96%+/-2.76% than those in control group 4.25%+/-0.65% and 2.33%+/
      1.09%, respectively (P<0.01). The apoptosis rate and Fas expression of HK-2 in
      HBV DNA positive serum group was significantly higher than those in HBV DNA
      negative serum (P<0.01). Apoptosis rate of HK-2 cells in HBV DNA positive serum
      group was positively correlated with the level of HBV-DNA (r = 0.657). The level
      of serum TGF-beta (1) in CHB group was 163.05+/-91.35 microg/L, significantly
      higher as compared with 81.40+/-40.75 microg/L in the control group (P<0.01).
      CONCLUSION: The serum of patients with chronic hepatitis B promotes apoptotic
      damage in human renal tubular cells by triggering a pathway of Fas up-regulation.
      HBV and TGF-beta (1) may play important roles in the mechanism of hepatitis B
      virus associated glomerulonephritis.

PMID- 16586547
TI  - Morphological observation of tumor infiltrating immunocytes in human rectal
      cancer.
AB  - AIM: To investigate the morphological characterization of tumor infiltrating
      dendritic cells (TIDCs) and tumor infiltrating lymphocytes (TILs) in human rectal
      cancer. METHODS: Light and electron microscopy as well as immunohistochemistry
      were used to observe the distributive and morphological changes of TIDCs and
      TILs. RESULTS: TIDCs were mainly located in tumor-surrounding tissue. The number
      of TIDCs in the earlier stage was higher than that in the later stage (P<0.01).
      TILs were mainly seen in adjacent tissue of cancers and tumor-surrounding tissue.
      There were more TILs in the earlier stage than that in the later stage (P<0.01).
      Under electron microscope, TIDCs were irregular in shape and exhibited many
      dendritic protrusions. It is not obvious that cancer cells perforated the
      basement membrane and TILs were arranged along the basement membrane in the
      earlier stage. In the later stage, it is explicit that cancer cells perforated
      the basement membrane and surrounded by TILs. There were contacts among TIDCs,
      TILs and tumor cell. One TIDCs contacted one or several TILs which clustered
      around TIDCs. Glycogen granules were seen between TIDCs and TILs. CONCLUSION: The
      number of TIDCs and TILs is related with tumor progression There exist close
      relationships among TIDCs, TILs and tumor cell.

PMID- 16586548
TI  - Effect of electro-acupuncture at Foot-Yangming Meridian on somatostatin and
      expression of somatostatin receptor genes in rabbits with gastric ulcer.
AB  - AIM: To discuss the protective effect of electroacupuncture at the Foot-Yangming
      Meridian on gastric mucosal lesion, somatostatin (SS) and the expression of SS
      receptor genes (SSR(1)mRNA ) in rabbits with gastric ulcer and to further explore
      the relative specificity of meridians and viscera at gene expression level.
      METHODS: Forty rabbits were randomly divided into control group (A), gastric
      ulcer model group (B), Foot-Yangming Meridian group (C), Foot-Shaoyang Meridian
      group (D) and Foot-Taiyang Meridian group (E). The gastric ulcer model was
      prepared by infusing alcohol into stomach. Groups C-E were treated with electro
      acupuncture at points along the above meridians using meridian stimulating
      instruments for 7 d respectively. By the end of treatment, the index of gastric
      ulcer was determined, the amount of epidermal growth factor(EGF) and somatostatin
      was measured by radioimmunoassay (RIA). SS-R(1)mRNA expression in gastric mucosa
      was determined by RT-PCR. RESULTS: The value of EGF in model group was obviously
      lower (73.6+/-14.8 vs 91.3+/-14.9 pg/mL, P<0.01) than that in control group. The
      index of gastric ulcer, content of SS and expression of SSR1mRNA in gastric
      mucosa were significantly higher than those in control group (24.88+/-6.29 vs
      8.50+/-2.98 scores, P<0.01; 2978.6+/-587.6 vs 1852.4+/-361.7 mIU/mL, P<0.01;
      2.56+/-0.25 vs 1.04+/-0.36, P<0.01). The value of EGF in Foot-Yangming Meridian
      group was higher than that in model group (92.2+/-6.7 vs 73.6+/-14.8 pg/mL,
      P<0.01). The index of gastric ulcer, content of SS and expression of SS-R(1)mRNA
      in gastric mucosa were significantly lower than those in control group (10.88+/
      3.23 vs 24.88+/-6.29 scores, P<0.01; 1800.2+/-488 vs 2978.6+/-587.6 mIU/mL,
      P<0.01; 1.07+/-0.08 vs 2.56+/-0.25 mIU/mL, P<0.01). Compared to the model group,
      the content of SS and expression of SSR1mRNA in gastric mucosa in Foot-Shaoyang
      Meridian group decreased (2441.0+/-488.vs 2978.6+/-587.6 mIU/mL, P<0.05;1.73+/
      0.16 vs 2.56+/-0.25 mIU/mL, P<0.01). But the above parameters in Foot-Taiyang
      Meridian group did not improve and were significantly different from those in
      Foot-Yangming Meridian group (P<0.05). CONCLUSION: Electro-acupuncture at Foot
      Yangming Meridian can protect gastric mucosa against injury. The mechanism may be
      related to the regulation of brain-gut peptides and the expression of SSR(1)mRNA.

PMID- 16586549
TI  - Cyclin D1 antisense oligodexoyneucleotides inhibits growth and enhances
      chemosensitivity in gastric carcinoma cells.
AB  - AIM: To examine the effects of cyclin D1 antisense oligodexoyneucleotides (ASODN)
      on growth and chemosensitivity of gastric carcinoma cell lines SGC7901 and its
      mechanism. METHODS: Phosphorothioate modified cyclin D1 ASODN was encapsulated by
      LipofectAMINE2000 (LF2000) and transfected into cells, the dose-effect curves and
      growth curves were observed. 5-FU, MTX, CDDP of different concentrations were
      given after transfecting cells with cyclin D1 ASODN for 24 h the dose-effect
      responses were observed and IC50s were calculated. The mRNA expression of cyclin
      D1, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydrofolate
      reductase (DHFR) was detected by reverse transcription-PCR (RT-PCR) at 24 h and
      48 h after transfection. RESULTS: Dose-dependent inhibitory effect was caused by
      cyclin D1 ASODN in SGC7901 cells. Transfecting gastric carcinoma cells with 0.2
      micromol/L cyclin D1 ASODN for 24 h could inhibit growth significantly and reduce
      expression of cyclin D1 mRNA. Cyclin D1 ASODN could increase the chemosensitivity
      to 5-FU, MTX, CDDP in cells. The IC50s of different chemotherapeutic agents in
      ASODN plus chemotherapy groups were significantly lower than those in controls.
      Transfection with cyclin D1 ASODN leaded to an increase in TS and DHFR mRNA and a
      decrease in TP mRNA as determined by RT-PCR at 24 h, the alterations were more
      significant at 48 h. CONCLUSIONS: Cyclin D1 ASODN can decrease mRNA expression of
      cyclin D1, inhibit growth and enhance the chemosensitivity by changing the
      expression of enzymes related to metabolism of chemotherapeutic agents in SGC7901
      gastric carcinoma cells.

PMID- 16586550
TI  - Effect of drug treatment on hyperplastic gastric polyps infected with
      Helicobacter pylori: a randomized, controlled trial.
AB  - AIM: To study the effects of drug treatment on hyperplastic gastric polyps
      infected with Helicobacter pylori (H pylori). METHODS: Forty-eight patients with
      hyperplastic gastric polyps (3-10 mm in diameter) infected with H pylori were
      randomly assigned to a treatment group (n = 24) which received proton-pump
      inhibitor (omeprazole or lansoprazole), clarithromycin, bismuth citrate and
      tinidazole, and a control group (n = 24) which received protective agent of
      gastric mucosa (tepretone). Patients underwent endoscopy and H pylori examination
      regularly before enrollment and 1-12 mo after treatment. RESULTS: Twenty-two
      patients in the treatment group and 21 in the control group completed the entire
      test protocol. In the treatment group, polyps disappeared 1-12 mo (average, 6.5+/
      1.1 mo) after the treatment in 15 of 22 patients (68.2%) and H pylori infection
      was eradicated in 19 of the 22 patients (86.4%). However, 12 months after the
      study, no change in polyps or H pylori status was seen in any controls
      ((b)P<0.01). CONCLUSION: Most hyperplastic gastric polyps disappear after
      eradication of H pylori.

PMID- 16586551
TI  - Melanoma differentiation-associated gene-7, MDA-7/IL-24, selectively induces
      growth suppression, apoptosis in human hepatocellular carcinoma cell line HepG2
      by replication-incompetent adenovirus vector.
AB  - AIM: To investigate the effect of replication-incompetent adenovirus vector
      expressing MDA-7/IL-24 on tumor growth and apoptosis in human hepatocellular
      carcinoma (HCC) cell line HepG2 and normal liver cell line L02. METHODS: We
      constructed the recombinant replication-incompetent Ad.mda-7 virus vector and
      infected it into the human HCC cell line HepG2 and normal liver cell line L02. RT
      PCR was performed to detect the mRNA expressing in cells. by ELISA was used to
      detect MDA-7/IL-24 protein expression in the culture supernatant. The effect of
      apoptosis induced by Ad.mda-7 was confirmed by Hoechst staining and flow
      cytometry assay with Annexin-V and PI staining. MTT assay was used to determine
      growth inhibition of HepG2 cells, and cell-cycle and hypodiploidy analyses were
      performed by flow cytometry. RESULTS: Recombinant replication-defective virus
      expressing MDA-7/IL-24 was constructed successfully. RT-PCR showed that the
      Ad.mda-7 could mediate the expression of the exogenous gene MDA-7/IL-24 into
      HepG2 and L02. The concentration of MDA-7/IL-24 protein in supernatant was 130
      pg/mL and 110 pg/mL in Ad.mda-7-infected L02 and HepG2 cells, respectively.
      Ad.mda-7 infection obviously induced apoptosis (from 2.60%+/-0.72% to 33.6%+/
      13.2%, P=0.00012) and growth suppression in HepG2 (inhibition ratio IR=68%) and
      an increase in the percentage of specific cancer cell types at the G2/M phase of
      the cell cycle (from 6.44% to 32.29%, P<0.01), but not in L02 cells. CONCLUSION:
      These results confirm selectively induction of apoptosis and growth suppression
      by the mda-7/IL-24 gene with replication-incompetent adenovirus vector in human
      hepatocellular carcinoma cell line HepG2.

PMID- 16586552
TI  - Tubulovillous adenoma of anal canal: a case report.
AB  - Tumors arising from the anal canal are usually of epithelial origin and are
      mostly squamous cell carcinoma or basal cell carcinoma. We present a case of
      benign anal adenomas arising from the anus, an extremely rare diagnosis. A 78
      year-old white man presented with rectal bleeding of several months duration.
      Examination revealed a 4 cm friable mass attached to the anus by a stalk. At
      surgery, the mass was grasped with a Babcock forceps and was resected using
      electrocautery. Microscopic examination revealed a tubulovillus adenoma with no
      areas of high grade dysplasia or malignant transformation. The squamocolumnar
      junction was visible at the edges of the lesion confirming the anal origin of the
      tumor. We believe the tubulovillus adenoma arose from either an anal gland or its
      duct that opens into the anus. Although seen rarely, it is important to recognize
      and treat these tumors at an early stage because of their potential to transform
      into adenocarcinoma.

PMID- 16586553
TI  - Acute biliary pancreatitis and cholecystolithiasis in a child: one time treatment
      with laparoendoscopic "rendez-vous" procedure.
AB  - Acute biliary pancreatitis (ABP) is rare in childhood and endoscopic
      sphincterotomy should be avoided in the child due to the risk of both early and
      late complications but, when necessary, the optimal timing between endoscopic
      procedure and cholecystectomy is still uncertain. A nine years old child with
      acute biliary pancreatitis underwent successful laparo-endoscopic "Rendez-Vous"
      procedure in which endoscopic drainage of the common bile duct and laparoscopic
      cholecystectomy were performed simultaneously. This is the first case reported of
      laparo-endoscopic Rendez-Vous in a child. The excellent outcome of this patient
      and the review of the literature concerning other available options for the
      treatment of such cases suggest that this procedure offers great advantages,
      especially in children, of reducing the required number of treatments, the risk
      of ineffectiveness, the number of anaesthesia, the length of hospital stay and
      the risk of iatrogenic morbidity.

PMID- 16586554
TI  - Complete pancreatic heterotopia of gallbladder with hypertrophic duct simulating
      an adenomyoma.
AB  - The gallbladder is an unusual location of pancreatic heterotopia, defined as the
      presence of pancreatic tissue lacking anatomical and vascular continuity with the
      main body of the gland. A 28-year-old man presented with anorexia, nausea and
      pain in the right upper abdomen. On physical examination, the abdomen was tender
      to palpation and Murphy sign was positive. The patient underwent a
      cholecystecomy. This case, in our opinion, is very interesting since it permits
      to consider a controversial issue in the pathology of the gallbladder. The
      histological appearance of ductal structure in pancreatic heterotopia resembles
      the histological picture of both Aschoff-Rokitansky (AR) sinuses and adenomyomas.
      This finding suggests that these lesions are linked by a common histogenetic
      origin. We suggest that the finding of an adenomyoma in the gallbladder should
      prompt an extensive sampling of the organ in order to verify the coexistence of
      pancreatic rests.

PMID- 16586555
TI  - Fatty liver in H63D homozygotes with hyperferritinemia.
AB  - To study the clinical correlates of the H63D mutation we have analysed the
      phenotype of H63D homo-zygotes identified through mutation analysis in a referral
      laboratory. A total of 366 blood samples referred for HFE analysis were screened
      for C282Y and H63D mutations. Four H63D homozygotes were identified. All had
      raised serum ferritin but normal transferrin saturation. They were negative for
      hepatitis B and C and only one patient consumed excess alcohol. In all 4 cases
      ultrasonography revealed fatty liver. In two patients a liver biopsy was done and
      showed mild siderosis with an unusual distribution and macrovesicular steatosis.
      These data confirm the association between fatty liver, hyperferritinaemia and
      increased hepatic iron, but do not clarify whether siderosis was related to
      steatosis rather than homozygosity for the H63D mutation. Patients with fatty
      liver may complicate the interpretation of data in population studies of the
      expression of H63D homozygosity.

PMID- 16586556
TI  - Hepatic encephalopathy with status epileptics: a case report.
AB  - A 62-year-old male with decompensated liver cirrhosis due to hepatitis C virus
      developed severe hepatic encephalopathy with status epilepticus. The blood
      ammonia level on admission was more than twice the normal level. Brain computed
      tomography and magnetic resonance imaging were normal. In addition,
      electroencephalogram showed diffuse sharp waves, consistent with hepatic
      encephalopathy. The status epilepticus was resolved after antiepileptic therapy
      (phenytoin sodium) and treatment for hepatic encephalopathy (Branched chain amino
      acids). The blood ammonia level normalized with the clinical improvement and the
      patient did not have a recurrence of status epilepticus after the end of the
      antiepileptic treatment. Additionally, the electroencephalogram showed normal
      findings. Thus, we diagnosed the patient as hepatic encephalopathy with status
      epilepticus. We consider the status epilepticus of this patient to a rare and
      interesting finding in hepatic encephalopathy.

PMID- 16586557
TI  - Left paraduodenal hernia in an adult complicated by ascending colon cancer: a
      case report.
AB  - Paraduodenal hernia is the most common internal hernia. The clinical symptoms of
      paraduodenal hernia may be intermittent and nonspecific. Therefore, it is
      difficult to diagnose preoperatively. Abdominal computed tomography (CT) scan
      currently plays an important role in the evaluation and management of
      paraduodenal hernia before surgical operation. We report one unique case of
      preoperatively diagnosed left paraduodenal hernia complicated by advanced
      ascending colon cancer and reviews of Japanese literature.

PMID- 16586558
TI  - Destructive granuloma derived from a liver cyst: a case report.
AB  - We herein report the case of an idiopathic liver cystic mass which aggressively
      infiltrated the thoraco-abdominal wall. A 74-year-old woman who had a huge cystic
      lesion in her right hepatic lobe was transferred to our hospital for further
      examinations. Imaging studies revealed a simple liver cyst, and the cytological
      findings of intracystic fluid were negative. She was followed up periodically by
      computed tomography (CT) scans. Seven years later, she complained of a prominence
      and dull pain in her right thoraco-abdominal region. CT revealed an enlargement
      of the cystic lesion and infiltration into the intercostal subcutaneous tissue.
      We suspected the development of a malignancy inside the liver cyst such as
      cystadenocarcinoma, and she therefore underwent surgery. A tumor extirpation was
      performed, including the chest wall, from the 7th to the 10th rib, as well as a
      right hepatic lobectomy. Pathologically, the lesion consisted of severe
      inflammatory change with epithelioid cell granuloma and bone destruction without
      any malignant neoplasm. No specific pathogens were evident based on further
      histological and molecular examinations. Therefore the lesion was diagnosed to be
      a destructive granuloma associated with a long-standing hepatic cyst. Since
      undergoing surgery, the patient has been doing well without any signs of
      recurrence.

PMID- 16586559
TI  - Acute pancreatitis associated with peroral double-balloon enteroscopy: a case
      report.
AB  - A 58-year-old Japanese man had tarry stool and severe anemia. Neither upper nor
      lower gastrointestinal (GI) endoscopy showed any localized lesions. Thus, the
      source of his GI bleeding was suspected to be in the small intestine, and he
      underwent peroral double-balloon enteroscopy (DBE) using EN-450T5 (Fujinon
      Toshiba ES System Co., Tokyo, Japan). There were no lesions considered to be the
      source of GI bleeding. After the procedure, the patient began to experience
      abdominal pain. Laboratory tests revealed hyperamylasemia and abdominal computed
      tomography revealed an inflammation of the pancreas and the peripancreas. He was
      thus diagnosed to have acute pancreatitis. Conservative treatments resulted in
      both clinical and laboratory amelioration. He had no history of alcohol
      ingestion, gallstone disease or pancreatitis. Magnetic resonance
      cholangiopancreatography demonstrated no structural alterations and no stones in
      the pancreatobiliary ductal system. As his abdominal pain started after the
      procedure, his acute pancreatitis was thus thought to have been related to the
      peroral DBE. This is the first reported case of acute pancreatitis probably
      associated with peroral DBE.

PMID- 16586561
TI  - Autoimmune pancreatitis: functional and morphological recovery after steroid
      therapy.
AB  - Autoimmune pancreatitis, a recently recognized type of chronic pancreatitis, is
      not rare in Japan, but reports of it elsewhere are relatively uncommon. We report
      the first preoperatively diagnosed case of autoimmune pancreatitis in Hungary,
      which responded well to steroid treatment and provided radiographic and
      functional evidence of this improvement. A 62-year-old female presented with a 4
      month history of recurrent epigastric pain and a 5-kg weight loss. The oral
      glucose tolerance test (OGTT) indicated diabetes mellitus and the result of the
      fecal elastase test was abnormal. Ultrasonography (US) and the CT scan
      demonstrated a diffusely enlarged pancreas, and endoscopic retrograde
      cholangiopancreatography (ERCP) an irregular main pancreatic duct with long
      strictures in the head and tail. Autoimmune pancreatitis was diagnosed. The
      patient was started on 32 mg prednisolone daily. After 4 wk, the OGTT and faecal
      elastase test results had normalized. The repeated US and CT scan revealed a
      marked improvement of the diffuse pancreatic swelling, while on repeated ERCP,
      the main pancreatic duct narrowing was seen to be ameliorated. It is important to
      be aware of this disease and its diagnosis, because AIP can clinically resemble
      pancreatobiliary malignancies, or chronic or acute pancreatitis. However, in
      contrast with chronic pancreatitis, its symptoms and morphologic and laboratory
      alterations are completely reversed by oral steroid therapy.

PMID- 16586560
TI  - Living-related liver transplantation for multiple liver metastases from rectal
      carcinoid tumor: a case report.
AB  - A 42-year-old woman was admitted to our hospital because of multiple liver tumors
      detected by ultrasonography. Colonoscopy revealed submucosal tumor in the rectum,
      which was considered the primary lesion. Endoscopic mucosal resection followed by
      histopathological examination revealed that the tumor was carcinoid. The resected
      margin of the tumor was positive for malignant cells. Two courses to
      transcatheter arterial chemotherapy for liver metastasis were ineffective.
      Accordingly, the rectal tumor and metastatic lymph nodes were surgically
      resected. One month after the operation, she received liver transplantation (left
      lateral segment and caudate lobe) from her son. No recurrent lesion has been
      observed at two years after the liver transplantation. Liver transplantation
      should be considered as a treatment option even in advanced case of carcinoid
      metastasis to the liver. We also discuss the literature on liver transplantation
      for metastatic carcinoid tumor.

PMID- 16586562
TI  - Sporadic somatic mutation of c-kit gene in a family with gastrointestinal stromal
      tumors without cutaneous hyperpigmentation.
AB  - We described two members in a family with gastrointestinal stromal tumors (GISTs)
      without cutaneous hyperpigmentation. The patients were father and son who did not
      have cutaneous hyperpigmentation. Histological examination showed that these
      tumors were GISTs expressing CD34 and CD117. Tumor DNA extracted from paraffin
      embedded specimens revealed somatic mutation with a deletion mutation at
      different codons in exon 11 of c-kit gene after direct sequencing analysis. No
      germline mutation was detected in DNA extracted from peripheral leukocytes
      obtained from the father and son. We propose that GISTs could be caused by
      sporadic somatic mutation in a family without germline mutation and
      hyperpigmentation.

PMID- 16586564
TI  - Merkel's move on science.

PMID- 16586563
TI  - The Black Report: health inequalities 25 years on.

PMID- 16586565
TI  - Big moth numbers dwindle.

PMID- 16586566
TI  - Paul Katz.

PMID- 16586567
TI  - Years of "frozen conflict" leave Abkhazia isolated and poor.

PMID- 16586568
TI  - Czech health workers call for minister to be sacked.

PMID- 16586569
TI  - [9th Conference of Francophone Mycobacteriology, Montpellier, September 28-30,
      2005].

PMID- 16586571
TI  - A la carte coverage turns benes into bargain hunters.

PMID- 16586573
TI  - Preliminary Note on Nebular Proper Motions.

PMID- 16586572
TI  - Recent Progress in the Theories of Modular and Formal Invariants and in Modular
      Geometry.

PMID- 16586574
TI  - Discovery of the Ninth Satellite of Jupiter.

PMID- 16586575
TI  - Spherical Abberation in Astronomical Objectives Due to the Changes of
      Temperature.

PMID- 16586576
TI  - On the Relation Between the Proper Motions and the Radial Velocities of the Stars
      of the Spectral Types F, G, K, and M.

PMID- 16586577
TI  - Critique of the Hypothesis of Anomalous Dispersion in Certain Solar Phenomena.

PMID- 16586578
TI  - A Revision of the Atomic Weight of Cadmium.

PMID- 16586579
TI  - Phoradendron.

PMID- 16586580
TI  - The Morphology and Relationships of Podomitrium Malaccense. (Steph.).

PMID- 16586581
TI  - The Feebly Inhibited: I. Violent Temper and Its Inheritance.

PMID- 16586582
TI  - The English Rabbit and the Question of Mendelian Unit-Character Constancy.

PMID- 16586583
TI  - The Synthesis of Triad Systems Delta in t Elements in Particular for t = 31.

PMID- 16586584
TI  - On the Identity of Heliotropism in Animals and Plants.

PMID- 16586585
TI  - Archaeology of Barbados.

PMID- 16586586
TI  - Culture of the North American Indians Occupying the Caribou Area and its Relation
      to Other Types of Culture.

PMID- 16586587
TI  - The phi-Subgroup of a Group of Finite Order.

PMID- 16586588
TI  - On the Radial Velocities of Nebulae.

PMID- 16586589
TI  - The Basal Caloric Output of Vegetarians as Compared with that of Non-Vegetarians
      of Like Weight and Height.

PMID- 16586590
TI  - The Influence of Athletic Training Upon Basal Metabolism.

PMID- 16586591
TI  - A Comparison of the Basal Metabolism of Normal Men and Women.

PMID- 16586592
TI  - The Factors Affecting Normal Basal Metabolism.

PMID- 16586593
TI  - On the Nature of the Nerve Impulse.

PMID- 16586594
TI  - A Point Scale for Measuring Mental Ability.

PMID- 16586595
TI  - Color Vision in the Ring-Dove (Tutur risorius).

PMID- 16586596
TI  - The Feebly Inhibited: II. Nomadism or the Wandering Impulse with Special
      Reference to Heredity.

PMID- 16586597
TI  - Conjugate Systems of Space Curves with Equal Laplace-Darboux Invariants.

PMID- 16586598
TI  - Transformation of Surfaces.

PMID- 16586599
TI  - Potassium Ammono Argenate, Barate, Calciate, and Sodate.

PMID- 16586600
TI  - Metallic Salts of Ammono Acids.

PMID- 16586601
TI  - Ammonobasic Iodides of Aluminium.

PMID- 16586602
TI  - A Revision of the Atomic Weight of Lead: The Analysis of Lead Bromide and
      Chloride.

PMID- 16586604
TI  - On the Earth Considered as a Heat Engine.

PMID- 16586603
TI  - A Revision of the Atomic Weight of Praseodymium.

PMID- 16586605
TI  - A Phylogenetic Study of Cycads.

PMID- 16586607
TI  - An Interpretation of Self-Sterility.

PMID- 16586606
TI  - Dimorphism in Size of Spermatozoa and its Relation to the Chromosomes.

PMID- 16586608
TI  - Discovery of Eight Variable Stellar Spectra.

PMID- 16586609
TI  - On the Linear Dependence of Functions of Several Variables, and Certain
      Completely Integrable Systems of Partial Differential Equations.

PMID- 16586610
TI  - Systematic Motion among Stars of the Helium Type.

PMID- 16586611
TI  - The Abundance of the Elements in Relation to the Hydrogen-Helium Structure of the
      Atoms.

PMID- 16586612
TI  - The Genetic Relations of Certain Forms in American Aboriginal Art.

PMID- 16586613
TI  - The Situation in Regard to Rowland's Preliminary Table of Solar Spectrum Wave
      Lengths.

PMID- 16586614
TI  - Changes in the Form of the Nebula N. G. C. 2261.

PMID- 16586615
TI  - On the Effect of Removal of the Pronephros of the Amphibian Embryo.

PMID- 16586616
TI  - On the Presence of a Median Eye in Trilobites.

PMID- 16586617
TI  - The Nature of Mechanical Stimulation.

PMID- 16586618
TI  - Hereditary Reaction-System Relations: An Extension of Mendelian Concepts.

PMID- 16586619
TI  - Point Sets and Allied Cremona Groups: Part II.

PMID- 16586620
TI  - On a Theorem of Lucas.

PMID- 16586621
TI  - Interpretation of the Simplest Integral Invariant of Projective Geometry.

PMID- 16586623
TI  - The Absorption Coefficients of Soft X Rays.

PMID- 16586622
TI  - Size Inheritance in Guinea-Pig Crosses.

PMID- 16586624
TI  - Further Evidence as to the Relation Between Crown Gall and Cancer.

PMID- 16586625
TI  - Locomotion of Sea-Anemones.

PMID- 16586626
TI  - The Behavior of Sea-Anemones.

PMID- 16586627
TI  - A Contribution to the Petrography of Japan.

PMID- 16586628
TI  - Is There a Temperature Coefficient for the Duration of Life?

PMID- 16586629
TI  - On the Suggested Mutual Repulsion of Fraunhofer Lines.

PMID- 16586631
TI  - Synthesis of the Base C(3)H(4)ON(2) Derived from Methyl-Aminomethyl-3,4
      Dihydroxyphenylcarbinol.

PMID- 16586630
TI  - An Attempt to Detect the Mutual Influence of Neighboring Lines in Electric
      Furnace Spectra Showing Anomalous Dispersion.

PMID- 16586632
TI  - Extinguished and Resurgent Coral Reefs.

PMID- 16586633
TI  - The Origin of Certain Fiji Atolls.

PMID- 16586635
TI  - On the Inheritance of Certain Glume Characters in the Cross Avena Fatua x A.
      Sativa var. Kherson.

PMID- 16586634
TI  - Interferometer Methods Based on the Cleavage of a Diffracted Ray.

PMID- 16586636
TI  - A Comparison of the Rates of Regeneration from Old and from New Tissue.

PMID- 16586638
TI  - The Geologic Role of Phosphorus.

PMID- 16586637
TI  - The Effect of Successive Removal Upon the Rate of Regeneration.

PMID- 16586639
TI  - Dominantly Fluviatile Origin Under Seasonal Rainfall of the Old Red Sandstone.

PMID- 16586640
TI  - The Influence of Silurian-Devonian Climates on the Rise of Air-Breathing
      Vertebrates.

PMID- 16586642
TI  - The Mechanism of Diffusion of Electrolytes Through Animal Membranes.

PMID- 16586641
TI  - Density of Radio-Lead from Pure Norwegian Cleveite.

PMID- 16586643
TI  - The Rotation and Radial Velocity of the Spiral Nebula N. G. C. 4594.

PMID- 16586644
TI  - A Simple Method for Determining the Colors of the Stars.

PMID- 16586645
TI  - Studies of Magnitudes in Star Clusters: III. The Colors of the Brighter Stars in
      Four Globular Systems.

PMID- 16586647
TI  - A Proof of White's Porism.

PMID- 16586646
TI  - The Effect of an Electric Field on the Lines of Lithium and Calcium.

PMID- 16586648
TI  - A Contribution to the Petrography of the Philippine Islands.

PMID- 16586649
TI  - Salt Antagonism in Gelatine.

PMID- 16586651
TI  - On Certain Asymptotic Expressions in the Theory of Linear Differential Equations.

PMID- 16586650
TI  - Similarity in the Behavior of Protoplasm and Gelatin.

PMID- 16586652
TI  - On Newton's Method of Approximation.

PMID- 16586653
TI  - The Origin of Veins of the Asbestiform Minerals.

PMID- 16586654
TI  - A New Test of the Subsidence Theory of Coral Reefs.

PMID- 16586655
TI  - A New Thermometer Scale.

PMID- 16586656
TI  - On the Immunity Coloration of Some Nudibranchs.

PMID- 16586657
TI  - Some Effects of the Continued Administration of Alcohol to the Domestic Fowl,
      with Special Reference to the Progeny.

PMID- 16586659
TI  - Physiological Studies on Rhizophora.

PMID- 16586658
TI  - An Ionization Manometer.

PMID- 16586660
TI  - On the Hydrogen Ion Concentration of Sea Water, and the Physiological Effects of
      the Ions of Sea Water.

PMID- 16586661
TI  - Some Interrelations Between Diet, Growth, and the Chemical Composition of the
      Body.

PMID- 16586662
TI  - Further Study of the Atomic Weight of Lead of Radioactive Origin.

PMID- 16586663
TI  - On Some Anomalies in Geographic Distribution of Pacific Coast Mollusca.

PMID- 16586664
TI  - Some Psycho-Physiological Processes as Affected by Alcohol.

PMID- 16586665
TI  - The Influence of the Marginal Sense Organs on Metabolic Activity in Cassiopea
      Xamachana Bigelow.

PMID- 16586666
TI  - New Evidence in Regard to the Instability of Human Types.

PMID- 16586667
TI  - A Revision of the Atomic Weight of Tin.

PMID- 16586668
TI  - Further Studies of Nerve Conduction in Cassiopea.

PMID- 16586669
TI  - The Earliest Fresh-Water Arthropods.

PMID- 16586670
TI  - Observations upon Tropical Fishes and Inferences from their Adaptive Coloration.

PMID- 16586671
TI  - Notices of Biographical Memoirs.

PMID- 16586673
TI  - Research Grants from the Trust Funds of the Academy.

PMID- 16586672
TI  - Scientific Research for National Defense as Illustrated by the Problems of
      Aeronautics.

PMID- 16586674
TI  - Inferences Concerning Auroras.

PMID- 16586676
TI  - The Rate of Discharge of Central Neurones.

PMID- 16586675
TI  - The Resistance of Metals Under Pressure.

PMID- 16586677
TI  - A Physiological Study of Noctiluca, With Special Reference to Light Production,
      Anaesthesia and Specific Gravity.

PMID- 16586678
TI  - Physiographic Subdivision of the United States.

PMID- 16586680
TI  - Studies of the Magnitudes in Star Clusters: IV. On the Color of Stars in the
      Galactic Clouds Surrounding Messier II.

PMID- 16586679
TI  - On the Composition of the Medusa, Cassiopea Xamachana and the Changes in it After
      Starvation.

PMID- 16586681
TI  - The Color of the Standard Polor Stars Determined by the Method of Exposure
      Ratios.

PMID- 16586682
TI  - Terracing of Bajada Belts.

PMID- 16586683
TI  - Relation of the Apex of Solar Motion to Proper Motion and on the Cause of the
      Differences of its Position From Radial Velocities and Proper Motions.

PMID- 16586684
TI  - Hydrology of the Isthmus of Panama.

PMID- 16586685
TI  - The Meteor System of Pons-Winnecke's Comet.

PMID- 16586686
TI  - Improvements in Calorimetric Combustion, and the Heat of Combustion of Toluene.

PMID- 16586687
TI  - The Mass of the Electric Carrier in Copper, Silver and Aluminium.

PMID- 16586688
TI  - The Silver Voltameter as an International Standard for the Measurement of
      Electric Current.

PMID- 16586689
TI  - Application of the Laws of Action, Reaction and Interaction in Life Evolution.

PMID- 16586691
TI  - A Contribution to the Petrography of the Island of Bawean, Netherlands Indies.

PMID- 16586690
TI  - The Share of Egg and Sperm in Heredity.

PMID- 16586692
TI  - The Phylogenetic Development of Subapterous and Apterous Castes in the
      Formicidae.

PMID- 16586693
TI  - Refractivity Determined Irrespective of Form, by Displacement Interferometry.

PMID- 16586694
TI  - The Food of Drosophila Melanogaster Meigen.

PMID- 16586695
TI  - Temperature Optima for Human Energy.

PMID- 16586696
TI  - The Parallax of the Planetary Nebulae N. G. C. 7662.

PMID- 16586697
TI  - Adult Hymenopterous Parasites Attached to the Body of Their Host.

PMID- 16586698
TI  - Atlantis and the Permanency of the North Atlantic Ocean Bottom.

PMID- 16586699
TI  - The Responses of Hydroids to Gravity.

PMID- 16586700
TI  - The Lips and the Nasal Apertures in the Gnathostome Fishes, and Their Homologues
      in the Higher Vertebrates.

PMID- 16586701
TI  - Natural and Isogonal Families of Curves on a Surface.

PMID- 16586702
TI  - Some Problems of Diophantine Approximation: The Series Sigma e (lambdan) and the
      Distribution of the Points (lambdan alpha).

PMID- 16586703
TI  - On Moseley's Law for X-Ray Spectra.

PMID- 16586704
TI  - A Note on the Fitting of Parabolas.

PMID- 16586705
TI  - Axes of Symmetry in Globular Clusters.

PMID- 16586706
TI  - A Re-determination of the Value of the Electron and of Related Constants.

PMID- 16586707
TI  - Body Pigmentation and Egg Production in the Fowl.

PMID- 16586708
TI  - Variability of Germ Cells of Sea Urchins.

PMID- 16586709
TI  - Transplantation of Limbs.

PMID- 16586710
TI  - The Shapes of Group Molecules Forming the Surfaces of Liquids.

PMID- 16586711
TI  - The Importance of the Water Contained in the Deeper Portions of the Subsoil.

PMID- 16586712
TI  - The Transformation of Pseudoglobulin into Euglobulin.

PMID- 16586713
TI  - A Case of Normal Embryonic Atresia of the Esophagus.

PMID- 16586714
TI  - Studies of Magnitudes in Star Clusters: V. Further Evidence of the Absence of
      Scattering of Light in Space.

PMID- 16586715
TI  - The History of the Primordial Germ Cells in the Loggerhead Turtle Embryo.

PMID- 16586716
TI  - Studies of Magnitudes in Star Clusters: VI. The Relation of Blue Stars and
      Variables to Galactic Planes.

PMID- 16586717
TI  - Zuni Chronology.

PMID- 16586718
TI  - The Age of the Bolivian Andes.

PMID- 16586719
TI  - Large Current-Ripples as Indicators of Paleogeography.

PMID- 16586720
TI  - The Bearing of Selection Experiments with Drosophila upon the Frequency of
      Germinal Changes.

PMID- 16586721
TI  - Pressure Phenomena Accompanying the Growth of Crystal.

PMID- 16586722
TI  - A New Method of Transforming Esters of alpha-Aminoacids into their Corresponding
      Isothiocyanate.

PMID- 16586723
TI  - The Geology of the Fiji Islands.

PMID- 16586724
TI  - Dominance of Linked Factors as a Means of Accounting for Heterosis.

PMID- 16586725
TI  - Chemically Induced Crowngalls.

PMID- 16586726
TI  - Dynamical Systems with Two Degrees of Freedom.

PMID- 16586727
TI  - Membership of the Committees of the Council.

PMID- 16586728
TI  - The Laws of Elastico-Viscous Flow.

PMID- 16586729
TI  - A New Equation of Continuity.

PMID- 16586730
TI  - The Classification of Vascular Plants.

PMID- 16586731
TI  - Displacement Interferometry in Connection with U-Tubes.

PMID- 16586732
TI  - Attempt to Separate the Isotopic Forms of Lead by Fractional Crystallization.

PMID- 16586733
TI  - Hybrids of Zea Tunicata and Zea Ramosa.

PMID- 16586734
TI  - Distribution of Gall Midges.

PMID- 16586736
TI  - A Kinetic Hypothesis to Explain the Function of Electrons in the Chemical
      Combination of Atoms.

PMID- 16586735
TI  - Fertility and Age in the Domestic Fowl.

PMID- 16586737
TI  - Transverse Displacement Interferometry.

PMID- 16586738
TI  - The Proteins of the Peanut, Arachis Hypogaea.

PMID- 16586740
TI  - The Equilibrium Between Carbon Monoxide, Carbon Dioxide, Sulfur Dioxide, and Free
      Sulfur.

PMID- 16586739
TI  - A Design-Sequence from New Mexico.

PMID- 16586741
TI  - Physiological Effect on Growth and Reproduction of Rations Balanced from
      Restricted Sources.

PMID- 16586742
TI  - What Determines the Duration of Life in Metazoa?

PMID- 16586743
TI  - The Interrelation Between Diet and Body Condition and the Energy Production
      During Mechanical Work in the Dog.

PMID- 16586744
TI  - Heliotropic Animals as Photometers on the Basis of the Validity of the Bunsen
      Roscoe Law for Heliotropic Reactions.

PMID- 16586745
TI  - The Appearance of Reverse Mutations in the Bar-Eyed Race of Drosophila Under
      Experimental Control.

PMID- 16586746
TI  - The Part Played by Alcyonaria in the Formation of Some Pacific Coral Reefs.

PMID- 16586747
TI  - Observations Upon the Alkalinity of the Surface Water of the Tropical Pacific.

PMID- 16586748
TI  - The Effect of Temperature on Linkage in the Second Chromosome of Drosophila.

PMID- 16586749
TI  - Genetic Factors Affecting the Strength of Linkage in Drosophila.

PMID- 16586750
TI  - Further Evidence on the Concentration of the Stars Toward the Galaxy.

PMID- 16586751
TI  - Theoretical Relations in the Interferometry of Small Angles.

PMID- 16586752
TI  - Inter-Periodic Correlation in the Egg Production of the Domestic Fowl.

PMID- 16586753
TI  - Two Laws Governing the Ionization of Strong Electrolytes in Dilute Solutions and
      a New Rule for Determining Equivalent Conductance at Infinite Dilution Derived
      from Conductivity Measurements with Extremely Diluted Solutions of Potassium
      Chlorite.

PMID- 16586754
TI  - On the Growth and Fecundity of Alcoholized Rats.

PMID- 16586755
TI  - On the General Theory of Curved Surfaces and Rectilinear Congruences.

PMID- 16586756
TI  - A Contribution to the Petrography of Southern Celebes.

PMID- 16586757
TI  - On the Non-Existence of Nervous Shell-Shock in Fishes and Marine Invertebrates.

PMID- 16586758
TI  - Chemical Differentiation of the Central Nervous System in Invertebrates.

PMID- 16586760
TI  - Changeable Coloration in Brachyura.

PMID- 16586759
TI  - Proof of the Muscle Tension Theory of Heliotropism.

PMID- 16586761
TI  - The Equilibrium of Tortugas Sea Water with Calcite and Aragonite.

PMID- 16586762
TI  - An Oenothera-Like Case in Drosophila.

PMID- 16586763
TI  - Is Death from High Temperature Due to the Accumulation of Acid in the Tissues?

PMID- 16586764
TI  - Incompatibility of Mutant Races in Drosophila.

PMID- 16586765
TI  - Absorption Effects in the Spiral Nebulae.

PMID- 16586766
TI  - The Synergetic Action of Electrolytes.

PMID- 16586767
TI  - Appetites and Aversions as Constituents of Instincts.

PMID- 16586768
TI  - Rapid Respiration after Death.

PMID- 16586769
TI  - The Means of Locomotion in Planarians.

PMID- 16586770
TI  - Diurnal Changes in the Sea at Tortugas, Florida.

PMID- 16586771
TI  - Note on Interfermometer Methods of Measuring the Elastics of Small Bodies.

PMID- 16586772
TI  - Sublacustrine Glacial Erosion in Montana.

PMID- 16586773
TI  - The Effect of Stretching on the Rate of Conduction in the Neuro-Muscular Network
      in Cassiopea.

PMID- 16586774
TI  - A Criticism of the Evidence for the Mutation Theory of De Vries from the Behavior
      of Species of Oenothera in Crosses and in Selfed Lines.

PMID- 16586775
TI  - The Spectra of Isotopes and the Vibration of Electrons in the Atom.

PMID- 16586776
TI  - The Effect of Oxygen Tension on the Metabolism of Cassiopea.

PMID- 16586777
TI  - Scientific Publications from Germany.

PMID- 16586778
TI  - The Scope and Work of the Botanical Raw Products Committee.

PMID- 16586779
TI  - The Basal Katabolism of Cattle and Other Species.

PMID- 16586780
TI  - The Validity of the Equation P = Tdv/dT in Thermo-Electricity.

PMID- 16586782
TI  - The Brain Weight in Relation to the Body Length and also the Partition of Non
      Protein Nitrogen, in the Brain of the Gray Snapper (Neomaenis griseus).

PMID- 16586781
TI  - On the Equations of the Rectangular Interferometer.

PMID- 16586783
TI  - The Rotation and Radial Velocity of the Central Part of the Andromeda Nebula.

PMID- 16586784
TI  - The Location of the Sun's Magnetic Axis.

PMID- 16586785
TI  - Resonance and Ionization Potentials for Electrons in Cadmium, Zinc, and Potassium
      Vapors.

PMID- 16586786
TI  - Terrestrial Temperature and Atmospheric Absorption.

PMID- 16586787
TI  - Mobilities of Ions in Vapors.

PMID- 16586788
TI  - A Contribution to the Petrography of the South Sea Islands.

PMID- 16586789
TI  - The Law Controlling the Quantity and Rate of Regeneration.

PMID- 16586791
TI  - Mobilities of Ions in Air, Hydrogen, and Nitrogen.

PMID- 16586790
TI  - Dynamical Aspects of Photosynthesis.

PMID- 16586792
TI  - Thermo-Electric Action with Dual Conduction of Electricity.

PMID- 16586793
TI  - Metaliferous Laterite in New Caledonia.

PMID- 16586794
TI  - A Comparison of Growth Changes in the Nervous System of the Rat with
      Corresponding Changes in the Nervous System of Man.

PMID- 16586795
TI  - Variation and Heredity During the Vegetative Reproduction of Arcella dentata.

PMID- 16586796
TI  - The Importance of Nivation as an Erosive Factor, and of Soil Flow as a
      Transporting Agency, in Northern Greenland.

PMID- 16586797
TI  - On the alpha-Holomorphisms of a Group.

PMID- 16586799
TI  - A Comparison of White and Colored Troops in Respect to Incidence of Disease.

PMID- 16586798
TI  - Note on the Self-Adjusting Interferometer in Relation to the Achromatic Fringes.

PMID- 16586800
TI  - Perturbations and Tables of the Minor Planets Discovered by James C. Watson.

PMID- 16586801
TI  - Congenital Arterio-Venous and Lymphatico-Venous Fistulae. Unique Clinical and
      Experimental Observations.

PMID- 16586802
TI  - Tables of the Zonal Spherical Harmonic of the Second Kind Q(1)(z) and Q(1)'(z).

PMID- 16586803
TI  - On the Mean Age at Death of Centenarians.

PMID- 16586804
TI  - Calculating Ancestral Influence in Man: A Mathematical Measure of the
      Demonstrated Facts of Bi-Sexual Heredity.

PMID- 16586805
TI  - The Effect of Anesthetics on Living Cells.

PMID- 16586806
TI  - A General Sinking of Sea-Level in Recent Time.

PMID- 16586807
TI  - A Note on the Human Sex Ratio.

PMID- 16586808
TI  - The Existence of Homogeneous Groups of Large Ions.

PMID- 16586809
TI  - The Relation Between the Iso-Electric Point of a Globulin and Its Solubility and
      Acid Combining Capacity in Salt Solution.

PMID- 16586810
TI  - The Carbon Dioxide: Heat Ratio in Cattle.

PMID- 16586811
TI  - On Kummer's Memoir of 1857 Concerning Fermat's Last Theorem.

PMID- 16586812
TI  - An Improved Form of High Tension D. C. Apparatus.

PMID- 16586813
TI  - The Effect of the Concentration of Nitrates on the Reducing Powers of Bacteria.

PMID- 16586814
TI  - Positive Ray Analysis of Magnesium.

PMID- 16586815
TI  - The Energy Content of the Diapason.

PMID- 16586816
TI  - A Preliminary Note on the Results of Crossing Certain Varieties of Nicotiana
      Tabacum.

PMID- 16586817
TI  - The Correlation of Compound Formation, Ionization and Solubility in Solutions:
      Outline of a Modified Ionization Theory.

PMID- 16586818
TI  - The Pelter Effect.

PMID- 16586819
TI  - On the Roots of Bessel's Functions.

PMID- 16586820
TI  - The Diffusion of Air through Water in the Lapse of Years.

PMID- 16586821
TI  - The Influence of Age on Fertility in Swine.

PMID- 16586823
TI  - Measurement of the Diameter of Alpha-Orionis by the Interferometer.

PMID- 16586822
TI  - Variation and Inheritance in Size in Trypanosoma lewisi: 1. Life-cycle in the Rat
      and a Study of Size and Variation in "Pure Line" Infections.

PMID- 16586824
TI  - An Overlooked Infinite System of Groups of Order pq.

PMID- 16586825
TI  - The Globe, a Simple Trisomic Mutant in Datura.

PMID- 16586826
TI  - Studies of Magnitudes in Star Clusters: XIII. Variable Stars in N. G. C. 7006.

PMID- 16586827
TI  - The Skin Temperature of Pachyderms.

PMID- 16586829
TI  - Variation and Inheritance in Size in Trypanosoma Lewisi: II. The Effects of
      Growing "Pure Lines" in Different Vertebrate and Invertebrate Hosts and a Study
      of Size and Variation in Infections Occurring in Nature.

PMID- 16586828
TI  - Feeding Experiments with Mixtures of Foodstuffs in Unusual Proportions.

PMID- 16586830
TI  - Note on Moving Equilibra.

PMID- 16586831
TI  - A Formula for the Vicosity of Liquids.

PMID- 16586833
TI  - Changes Observed in the Crab Nebula in Taurus.

PMID- 16586832
TI  - The Angular Diameter of Alpha Bootis by the Interferometer.

PMID- 16586834
TI  - Linkage Variation and Chromosome Maps.

PMID- 16586835
TI  - Origin and History of the Bear Family in the Western Hemisphere, with Particular
      Reference to the Relation of This Question to Problems of Geographical History.

PMID- 16586836
TI  - An Unidentified Base among the Hydrolytic Products of Gelatin.

PMID- 16586837
TI  - Genetical and Cytological Proof of Non-disjunction of the Fourth Chromosome of
      Drosophila Melanogaster.

PMID- 16586838
TI  - Note on the Economic Conversion Factors of Energy.

PMID- 16586839
TI  - The Behavior of Homologous Chromosomes in a Triploid Canna.

PMID- 16586840
TI  - The Destruction of Phosphorescent Zinc Sulfides by Ultra Violet Light.

PMID- 16586841
TI  - Acoustic Pressure Distributions, Chiefly in Reservoirs and in Pipes.

PMID- 16586842
TI  - The Prediction of Annual Egg Production from the Records of Limited Periods.

PMID- 16586843
TI  - The Growth and Decay of Photo-thermionic Currents from Oxide Coated Filaments.

PMID- 16586844
TI  - Group of Isomorphisms of a Transitive Substitution Group.

PMID- 16586845
TI  - Einstein Static Fields Admitting a Group G(2) of Continuous Transformations into
      Themselves.

PMID- 16586846
TI  - Geometric Aspects of the Abelian Modular Functions of Genus Four (II).

PMID- 16586847
TI  - The Relation of Chalcedony to the Other Forms of Silica.

PMID- 16586848
TI  - Experiments with the Vacuum Gravitation Needle.

PMID- 16586849
TI  - The Frequency-sensitivity of Normal Ears.

PMID- 16586850
TI  - Coral Reefs of the Louisiade Archipelago.

PMID- 16586851
TI  - Structural Changes Associated with Factor Mutations and with Chromosome Mutations
      in Datura.

PMID- 16586853
TI  - Ricci's Principal Directions for a Riemann Space and the Einstein Theory.

PMID- 16586852
TI  - The Riemann Geometry and Its Generalization.

PMID- 16586854
TI  - Note on the Definition of a Lineal Functional.

PMID- 16586856
TI  - On Steering an Automobile around a Corner.

PMID- 16586855
TI  - Skin Transplantation in Frog Tadpoles.

PMID- 16586857
TI  - The Probable Error of the Vital Index of a Population.

PMID- 16586858
TI  - The Average Chemical Composition of Igneous Rocks.

PMID- 16586859
TI  - Dark Nebulae.

PMID- 16586860
TI  - Note on X-Ray Spectra.

PMID- 16586862
TI  - Acoustic Topography Varying with the Position of the Organ Pipe.

PMID- 16586861
TI  - A New Method of Using X-Rays in Crystal Analysis.

PMID- 16586863
TI  - The Physical Examination of Hearing and Binaural Aids for the Deaf.

PMID- 16586864
TI  - The Production of an E. M. F. on Closed Circuit by a Light Effect on Argentite.

PMID- 16586865
TI  - Positive and Negative Pinhole Resonators.

PMID- 16586866
TI  - The Evaluation of Quantum Integrals.

PMID- 16586867
TI  - Invisible Sun-Spots.

PMID- 16586868
TI  - Comparison of Theory with Observation for the Minor Planets 10 Hygiea and 175
      Andromache with Respect to Perturbations by Jupiter.

PMID- 16586869
TI  - A Method of Deriving the Distance of the A-Type Stars.

PMID- 16586870
TI  - The Larger Results of 20 Years of Solar Radiation Observations.

PMID- 16586871
TI  - Replantation of Entire Limbs without Suture of Vessels.

PMID- 16586872
TI  - Degeneration and Regeneration of the Lateral-line Organs in Amiurus Nebulosus.

PMID- 16586873
TI  - The Isolation of Pyrimidines from the Nucleic Acid of Tubercle Bacillus.

PMID- 16586874
TI  - The Relative Sensitivity of the Ear at Different Levels of Loudness.

PMID- 16586875
TI  - Normal Coordinates for the Geometry of Paths.

PMID- 16586876
TI  - Principal Directions in a Riemannian Space.

PMID- 16586877
TI  - Principal Directions in the Einstein Solar Field.

PMID- 16586878
TI  - Fields of Parallel Vectors in the Geometry of Paths.

PMID- 16586880
TI  - Animal Evolution.

PMID- 16586879
TI  - On the Influence of Density of Population Upon the Rate of Reproduction in
      Drosophila.

PMID- 16586881
TI  - The Correlation of Time Units and Climatic Changes in Peat Deposits of the United
      States and Europe.

PMID- 16586882
TI  - The Spectral Energy Distribution and Opacity of Wire Explosion Vapors.

PMID- 16586884
TI  - Number of Substitutions Omitting at Least one Letter in a Transitive Group.

PMID- 16586883
TI  - Spaces with Corresponding Paths.

PMID- 16586885
TI  - Photic Orientation in Insects.

PMID- 16586886
TI  - Hesperopithecus, the First Anthropoid Primate Found in America.

PMID- 16586887
TI  - Recent Discoveries on the Antiquity of Man.

PMID- 16586888
TI  - On the Measurement of a Physical Quantity Whose Magnitude is Influenced by
      Primary Causes beyond the Control of the Observer and on the Method of
      Determining the Relation between Two Such Quantities.

PMID- 16586889
TI  - Electronic Bombardment of Nickel.

PMID- 16586890
TI  - The Crystal Structure of Potassium.

PMID- 16586891
TI  - Preliminary Report on the Ionization of Potassium Vapor by Light.

PMID- 16586892
TI  - The Absorption of Light by Sodium and Potassium Vapors.

PMID- 16586893
TI  - The Meaning of Rotation in the Special Theory of Relativity.

PMID- 16586894
TI  - The Energy Losses Accompanying Ionization and Resonance in Mercury Vapor.

PMID- 16586895
TI  - The Crystal Structure of Beryllium and of Beryllium Oxide.

PMID- 16586896
TI  - Some Cases of Nerve Deafness and Their Bearing on Resonance Theories of Audition.

PMID- 16586897
TI  - The Quantitative Influences of Certain Factors Involved in the Production of
      Cyanosis.

PMID- 16586898
TI  - New Properties of All Real Functions.

PMID- 16586899
TI  - Generalized Limits in General Analysis.

PMID- 16586900
TI  - A Preliminary Note on Tetramitus, a Stage in the Life Cycle of a Coprozoic
      Amoeba.

PMID- 16586901
TI  - A Further Note on the Age Index of a Population.

PMID- 16586902
TI  - The Thermal Ionization of Gaseous Elements at High Temperatures: A Confirmation
      of the Saha Theory.

PMID- 16586903
TI  - An Electron Theory of Electric Conduction in Metals.

PMID- 16586905
TI  - On Riemann Spaces Conformal to Euclidean Space.

PMID- 16586904
TI  - Static Deflection, Logarithmic Decrement and First Semi-Period of the Vacuum
      Gravitation Needle.

PMID- 16586906
TI  - Some Extensions in the Mathematics of Hydromechanics.

PMID- 16586907
TI  - Hydrohepatosis, a Condition Analogous to Hydronephrosis.

PMID- 16586908
TI  - Novocaine and Curarisation.

PMID- 16586909
TI  - Undernutrition and Its Influence on the Metabolic Plane of Steers.

PMID- 16586910
TI  - A Quantum Theory of Optical Dispersion.

PMID- 16586911
TI  - Equiaffine Geometry of Paths.

PMID- 16586912
TI  - Circus Movements of Limulus.

PMID- 16586913
TI  - Affine Geometries of Paths Possessing an Invariant Integral.

PMID- 16586914
TI  - Closed Connected Sets Which Are Disconnected by the Removal of a Finite Number of
      Points.

PMID- 16586915
TI  - Note on an Experimental Problem of the Late A. G. Webster.

PMID- 16586916
TI  - A New Kind of Representation of Surfaces.

PMID- 16586917
TI  - The Electromagnetic Field and Curvature.

PMID- 16586918
TI  - On the Deformation of an n Cell.

PMID- 16586919
TI  - Control of the Appearance of Pupa-Larvae in Paedogenetic Diptera.

PMID- 16586920
TI  - The Wave-Lengths of Secondary X-Rays.

PMID- 16586921
TI  - The Wave-Lengths of Secondary X-Rays (Second note).

PMID- 16586922
TI  - Symbiosis between Termites and Their Intestinal Protozoa.

PMID- 16586923
TI  - The Absolute Weight of the Heart and the Spleen.

PMID- 16586924
TI  - The Nature of Resistance to Seedling Blight of Cereals.

PMID- 16586925
TI  - Election to the National Academy of Sciences: Pathways to membership.

PMID- 16586926
TI  - The Formation of the Lesser Antilles.

PMID- 16586927
TI  - Radio Fog Signals for the Protection of Navigation; Recent Progress.

PMID- 16586928
TI  - Selective Fertilization among the Gametes from the Same Individuals.

PMID- 16586929
TI  - The Japanese Rabbit and Gametic Purity.

PMID- 16586930
TI  - The Nature of Size Inheritance.

PMID- 16586932
TI  - The Influence of Alcohol on Duration of Life.

PMID- 16586931
TI  - A Statistical Discussion of Sets of Precise Astronomical Measurements: II.-Proper
      Motions.

PMID- 16586933
TI  - Two Extraordinary Larval Myrmecophiles from Panama.

PMID- 16586934
TI  - The Role of Adrenal Secretion in the Chemical Control of Body Temperature.

PMID- 16586935
TI  - Increase of Adrenal Secretion in Fever.

PMID- 16586936
TI  - An Explanation of the Gaps in the Distribution of the Asteroids According to
      Their Periods of Revolution.

PMID- 16586937
TI  - Note on the Difference in Velocity between Absolutely Bright and Faint Stars.

PMID- 16586938
TI  - On a Possible Relation between Globular Clusters and Stars of High Velocity.

PMID- 16586939
TI  - Note on Some Statistical Consequences of the Luminosity Law.

PMID- 16586940
TI  - Atmospheric Pulsation of the Cepheid Variable nu Aquilae.

PMID- 16586942
TI  - The Wave-Length of Molybdenum K(alpha) Rays when Scattered by Light Elements.

PMID- 16586941
TI  - On Parametric Representations of Continuous Surfaces.

PMID- 16586943
TI  - Quantization in Space and the Relative Intensities of the Components of Infra-Red
      Absorption Bands.

PMID- 16586944
TI  - The Ballistic (Air Resistance) Function.

PMID- 16586945
TI  - Ruppia and Its Environmental Factors.

PMID- 16586946
TI  - The Secondary Electrons Produced by Hard X-Rays in Light Elements.

PMID- 16586947
TI  - The Diffusion of Hydrogen into Air Measured by the Interferometer U-Gauge.

PMID- 16586948
TI  - White Light Interference Fringes with a Thick Glass Plate in One Path.

PMID- 16586950
TI  - On the Possibility of Identifying Chemical Processes in Living Matter.

PMID- 16586949
TI  - The Separation of Isotopes by the Ionic Migration Method.

PMID- 16586951
TI  - Concerning Sets of Segments Which Cover a Point Set in the Vitali Sense.

PMID- 16586952
TI  - Time Constants for Engineering Purposes in Simple Exponential Transient
      Phenomena.

PMID- 16586953
TI  - The Cordierite-Anthophyllite Mineralization at Blue Hill, Maine and Its Relation
      to Similar Occurrences.

PMID- 16586954
TI  - Resin Canals in the Evolution of the Conifers.

PMID- 16586955
TI  - The Origin of Parenchyma in Geological Time.

PMID- 16586956
TI  - Mortar Strength, A Problem of Practical Statistics.

PMID- 16586957
TI  - Skew-Growth Curves.

PMID- 16586958
TI  - Chemical Studies on Tuberculin.

PMID- 16586959
TI  - On Scattered Radiation Due to X-Rays from Molybdenum and Tungsten Targets.

PMID- 16586960
TI  - An Application of the Quantum Theory of Band Spectra to the First Negative
      Deslandres Group of Carbon.

PMID- 16586961
TI  - New Measurements of Planetary Radiation and Planetary Temperatures.

PMID- 16586962
TI  - The Number of Free Electrons with a Metal.

PMID- 16586963
TI  - Recent Measurements of the Joule Effect for CO(2).

PMID- 16586964
TI  - The Comet Tail Spectrum and Deslandres' First Negative Group.

PMID- 16586965
TI  - The Periodic Structural Regularities in Spectra as Related to the Periodic Law of
      the Chemical Elements.

PMID- 16586966
TI  - Notes on Neodymium Oxide.

PMID- 16586967
TI  - Gel Replacement, A New Aspect of Metasomatism.

PMID- 16586968
TI  - Halogen Isotopes and Infra-Red Reflection Spectra.

PMID- 16586969
TI  - The Compton Effect with No Box around the Tube.

PMID- 16586970
TI  - Compton Effect: Evidence on Its Relation to Duane's Box Effect.

PMID- 16586971
TI  - The Nature of the Association between Anthozoa and Zooxanthellae.

PMID- 16586972
TI  - The Mechanism of Reactions in the Urea Series.

PMID- 16586973
TI  - An Equation for the Haber Equilibrium.

PMID- 16586974
TI  - A Critical Potential of Methane and Its Absorption in the Ultra-Violet.

PMID- 16586975
TI  - Studies in Catalysis.

PMID- 16586977
TI  - Microchemical Color Reactions as an Aid to the Identification and Classification
      of Brain Tumors.

PMID- 16586976
TI  - On the Measurement of Critical Thermal Increment for Biological Processes.

PMID- 16586978
TI  - Virus Encephalitis in the Rabbit.

PMID- 16586979
TI  - Notes on Stellar Statistics: II: The Mathematical Expression of the Law of
      Tangential Velocities.

PMID- 16586980
TI  - Economics and the Calculus of Variations.

PMID- 16586981
TI  - Separable Quadratic Differential Forms and Einstein Solutions.

PMID- 16586982
TI  - On a New Method of Factorization.

PMID- 16586983
TI  - Functionals of Curves Admitting One-Parameter Groups of Infinitesimal Point
      Transformation.

PMID- 16586984
TI  - Conditions of Electric Equilibrium at Boundary Surfaces; Volta Effect.

PMID- 16586985
TI  - The Effect of a Surrounding Box on the Spectrum of Scattered X-Rays.

PMID- 16586986
TI  - The Significance of the Discovery of X-Ray Laws in the Field of Optics.

PMID- 16586987
TI  - The Compton Effect and Tertiary X-Radiation.

PMID- 16586988
TI  - The Age of the Stars.

PMID- 16586989
TI  - Notes on Stellar Statistics: III. On the Calculation of a Mean Absolute Magnitude
      from Apparent Magnitudes, Angular Proper Motions and Linear Radial Velocities.

PMID- 16586990
TI  - The Frequency Distribution on Apparent Magnitude of the Non-Magellanic O-Type
      Stars.

PMID- 16586991
TI  - The Population of New York City and Its Environs.

PMID- 16586993
TI  - The Rotating Disc.

PMID- 16586992
TI  - On the Intersection Invariants of a Manifold.

PMID- 16586994
TI  - Transitive Groups Involving Direct Products of Lower Degree.

PMID- 16586995
TI  - The Respiratory Function of the Hemocyanins.

PMID- 16586996
TI  - Prolonged Fasting as Affecting the Composition of Steer's Urine.

PMID- 16586997
TI  - The Torsion Problem of Curved Beams.

PMID- 16586998
TI  - A New Interpretation of the Hereditary Behavior of Self-Sterile Plants.

PMID- 16586999
TI  - A Note on the Abundance of Differential Combinants in a Fundamental System.

PMID- 16587000
TI  - On the Application of Borel's Method to the Summation of Fourier's Series.

PMID- 16587002
TI  - Continuous Transformations of Manifolds.

PMID- 16587001
TI  - Intersections of Complexes on Manifolds.

PMID- 16587003
TI  - Laws of Reciprocity and the First Case of Fermat's Last Theorem.

PMID- 16587004
TI  - A Species of Musa in the Tertiary of South America.

PMID- 16587005
TI  - Outlines of the History of the Recent Fauna of Palaearctic Asia.

PMID- 16587006
TI  - On the Mechanism of X-Ray Scattering.

PMID- 16587007
TI  - Ether-Drift Experiments at Mount Wilson.

PMID- 16587008
TI  - The Intensities of Lines in Multiplets: I. Theory.

PMID- 16587009
TI  - The Intensities of Lines in Multiplets: II. Observed Data.

PMID- 16587010
TI  - New Light on Two-Electron Jumps.

PMID- 16587011
TI  - The Anti-Sterility Vitamine Fat Soluble E.

PMID- 16587012
TI  - The Racial Factor in Metabolism.

PMID- 16587014
TI  - Activities of Colonial Animals: III. The Interrelation of Zooids in Soft Corals.

PMID- 16587013
TI  - Protoplasmic Action of Copper and Gold.

PMID- 16587015
TI  - Periodicity of Reproduction, Infection and Resistance in Bird Malaria.

PMID- 16587016
TI  - The Chromosomes of Zea Mays.

PMID- 16587017
TI  - Measurement of the Spectroscopic Binary Star Mizar with the Interferometer.

PMID- 16587018
TI  - Distribution of the Stars with Respect to Brightness and Distance from the Milky
      Way.

PMID- 16587019
TI  - The General Distribution of Cosmical Velocities.

PMID- 16587020
TI  - Human Metabolism in an Environment of Heated Air.

PMID- 16587021
TI  - Invariable Occurrence of Male Sterility with Dietaries Lacking Fat Soluble
      Vitamine E.

PMID- 16587022
TI  - A Histological Study of Sterility in the Albino Rat Due to a Dietary Deficiency.

PMID- 16587024
TI  - The Basin Range Problem.

PMID- 16587023
TI  - The Relativity Displacement of the Spectral Lines in the Companion of Sirius.

PMID- 16587025
TI  - The Separation of Rare Earths by the Ionic Migration Method.

PMID- 16587026
TI  - A Note on the Principle of Detailed Balancing.

PMID- 16587028
TI  - Fossil Plants from the Tertiary of Patagonia and Their Significance.

PMID- 16587027
TI  - The Measurement of the Absolute Charge on the Earth's Surface.

PMID- 16587029
TI  - Human Blood Groups and Their Bearing on Racial Relationships.

PMID- 16587030
TI  - Inductance Treated Acoustically by Differential Telephones.

PMID- 16587031
TI  - X-Ray Radiation from Hot Sparks.

PMID- 16587032
TI  - The Four Transverse Effects and Their Relations in Certain Metals.

PMID- 16587033
TI  - The Distribution of Energy in Thermal Radiation and the Law of Entire
      Equilibrium.

PMID- 16587034
TI  - Ionic Mobilities in Ether as a Function of Pressure.

PMID- 16587035
TI  - The Principle of Microscopic Reversibility.

PMID- 16587036
TI  - The Dynamical Function of the Tympanic Membrane and Its Associated Ossicles.

PMID- 16587037
TI  - A New Crystal for Wave-Length Measurements of Soft X-Rays.

PMID- 16587038
TI  - On Quasi-Analytic Functions.

PMID- 16587039
TI  - Sur le Calcul Approche des Integrales Definies.

PMID- 16587040
TI  - The Fixity of Basal Metabolism.

PMID- 16587041
TI  - Announcement of a Projective Theory of Affinely Connected Manifolds.

PMID- 16587042
TI  - Transformations of Einstein Spaces.

PMID- 16587043
TI  - On the Equi-projective Geometry of Paths.

PMID- 16587044
TI  - On Fluorescence Radiation of Nitrogen.

PMID- 16587045
TI  - X-Ray Spectra from a Ruled Reflection Grating.

PMID- 16587046
TI  - An Attempt to Test the Quantum Theory of X-Ray Scattering.

PMID- 16587047
TI  - The Viscosity of Liquids under Pressure.

PMID- 16587048
TI  - The Aging Effect in the Mobility of Positive Ions.

PMID- 16587049
TI  - Thermal Conductivity and Thermo-Electromotive Force of Single Metal Crystals.

PMID- 16587050
TI  - On the Quantum Theory of the Polarization of Resonance Radiation in Magnetic
      Fields.

PMID- 16587051
TI  - The Structure of the Hydrogen Molecule Ion.

PMID- 16587052
TI  - The Mechanism of Carbohydrate Utilization.

PMID- 16587053
TI  - The Separation of Chlorine into Isotopes (Isotopic Elements) and the Whole Number
      Rule for Atomic Weights.

PMID- 16587054
TI  - The Radioactivity of Potassium, Rubidium and Other Elements.

PMID- 16587055
TI  - The Oriented Wedge Theory of Emulsions.

PMID- 16587056
TI  - Polymolecular and Monomolecular Films.

PMID- 16587057
TI  - The Isotopic Composition of the Element Chlorine in the Meteorites: The Atomic
      Weight of Meteoric and Terrestrial Chlorine.

PMID- 16587058
TI  - The Effect of X-Rays on the Platinum Catalyst in the Contact Sulfuric Acid
      Reaction.

PMID- 16587060
TI  - A Statistical Approach to the Epidemiology of Cholera in Madras Presidency.

PMID- 16587059
TI  - The Japanese Waltzing Mouse, Its Origin and Genetics.

PMID- 16587061
TI  - The Distribution of Correlation Ratios Calculated from Random Data.

PMID- 16587062
TI  - The Life History of a Micro-Parasite Isolated from Carcinomatous Growths.

PMID- 16587063
TI  - Summary of Results and Proofs Concerning Fermat's Last Theorem.

PMID- 16587065
TI  - Concerning Certain Solvable Equations with Functional Derivatives.

PMID- 16587064
TI  - Mass in Curved Space-Time.

PMID- 16587066
TI  - First Integrals in the Geometry of Paths.

PMID- 16587068
TI  - Evidence for the Existence of Activated Molecules in a Chemical Reaction.

PMID- 16587067
TI  - Einstein's Recent Theory of Gravitation and Electricity.

PMID- 16587069
TI  - Crystalline Insulin.

PMID- 16587070
TI  - The Red Shift of Solar Lines and Relativity.

PMID- 16587072
TI  - Infra-Red Absorption of the N-H Bond.

PMID- 16587071
TI  - Some Relations of Environment to the Epidemiology and Control of Apple Scab.

PMID- 16587073
TI  - A Possible Explanation of the Relativity Doublets and Anomalous Zeeman Effect by
      Means of a Magnetic Electron.

PMID- 16587074
TI  - Theory of the Specific Heat of Electrolytes.

PMID- 16587075
TI  - The Spectrum of Neon in the Extreme Ultra-Violet.

PMID- 16587077
TI  - Subsidence Rate of Reef-Encircled Islands.

PMID- 16587076
TI  - The Free Path of Protons in Helium.

PMID- 16587078
TI  - The Compressibilities of Dunite and of Basalt Glass and Their Bearing on the
      Composition of the Earth.

PMID- 16587079
TI  - Radial Velocities of 368 Helium Stars.

PMID- 16587080
TI  - Visual Observations of the Solar Atmosphere.

PMID- 16587081
TI  - Capillary Condensation and Adsorption.

PMID- 16587082
TI  - The Physiological Principle of Minimum Work: II. Oxygen Exchange in Capillaries.

PMID- 16587083
TI  - Nuclear Division in the Trophozoites of Endamoeba Histolytica.

PMID- 16587084
TI  - The Effect of Hydrogen-Ion Concentration on Locomotion and Other Life-Processes
      in Amoeba Proteus.

PMID- 16587085
TI  - Pollen Abortion in Chromosomal Types of Datura.

PMID- 16587086
TI  - Remarks on Penetrating Radiation.

PMID- 16587087
TI  - New Evidence in Favor of a Dual Theory of Metallic Conduction.

PMID- 16587088
TI  - The Magnetic Moment of the Electron.

PMID- 16587089
TI  - A Theorem on Space Quantization.

PMID- 16587090
TI  - On the Heat Capacity of Non-Polar Solid Compounds.

PMID- 16587091
TI  - Systematic Relations between Electronic Structure and Band-Spectrum Structure in
      Diatomic Molecules: III. Molecule Formation and Molecular Structure.

PMID- 16587093
TI  - On Laguerre's Series: Third Note.

PMID- 16587092
TI  - On the Nature of Light.

PMID- 16587094
TI  - On Conformal Geometry.

PMID- 16587095
TI  - Concerning Indecomposable Continua and Continua Which Contain No Subsets That
      Separate the Plane.

PMID- 16587096
TI  - The Inquiline Fish Fierasfer at Key West, Florida.

PMID- 16587097
TI  - The Growth of Turtles.

PMID- 16587098
TI  - The Elder Peirce's.

PMID- 16587099
TI  - The Molecular Weights of Proteins in Phenol.

PMID- 16587101
TI  - Effects of an Electric Field upon the Radiating Hydrogen Atom.

PMID- 16587100
TI  - The Path of Light Quanta in an Interference Field.

PMID- 16587102
TI  - The Secondary Spectrum of Hydrogen and the Occurrence of H(3).

PMID- 16587103
TI  - Ionization of Mercury Vapor as a Function of the Intensity of Exciting Light.

PMID- 16587104
TI  - Doublets of Stripped Atoms of the Potassium Type.

PMID- 16587106
TI  - The Quantum Theory and the Behavior of Slow Electrons in Gases.

PMID- 16587105
TI  - The Electromagnetic Mass and Momentum of a Spinning Electron.

PMID- 16587107
TI  - Transfer of Energy from Electrons to Atoms.

PMID- 16587108
TI  - Form of the Number of the Prime Power Subgroups of an Abelian Group.

PMID- 16587110
TI  - The Absorption of X-Rays in Crystalline Compounds.

PMID- 16587109
TI  - The Solution of the Problem of the Simple Oscillator by a Combination of the
      Schroedinger and the Lanczos Theories.

PMID- 16587111
TI  - Acoustic Pressures in Case of Soap Bubbles.

PMID- 16587112
TI  - Acoustic Pressure Promoted by Cooperating Quill Tubes without Pinholes.

PMID- 16587113
TI  - Note on the Temperature Relations of Photo-Electric Emission and Thermionic
      Emission of Electrons.

PMID- 16587114
TI  - The Dielectric Constant of Diatomic Dipole-Gases on the New Quantum Mechanics.

PMID- 16587115
TI  - A Photo-Ionization Experiment with Hydrogen.

PMID- 16587116
TI  - Series and Ionization Potentials in the Iron Spectrum.

PMID- 16587117
TI  - The Location of the Electromotive Force in a Photo-Active Cell Containing a
      Fluorescent Electrolyte.

PMID- 16587119
TI  - The Mean Free Path of Electrons in Mercury Vapor.

PMID- 16587118
TI  - Remarks on Professor Lewis's Note on the Path of Light Quanta in an Interference
      Field.

PMID- 16587120
TI  - The Organic Content of Lake Water.

PMID- 16587121
TI  - The Stratigraphic Horizon of the Beds Containing Lepidocyclina Chaperi on Haut
      Chagres, Panama.

PMID- 16587122
TI  - The Electrical Conductivity of Liquid Cyanogen Bromide.

PMID- 16587123
TI  - On the Free Energy of Hydration of Ions.

PMID- 16587124
TI  - An Effect of Temperature and Age on Crossing-Over in the First Chromosome of
      Drosophila Melanogaster.

PMID- 16587125
TI  - Foraminifera from the Upper Eocene Deposits of the Coast of Ecuador.

PMID- 16587126
TI  - Maxwell's Equations and Atomic Dynamics.

PMID- 16587127
TI  - The Spectrum of Krypton in the Extreme Ultra-Violet.

PMID- 16587128
TI  - Some Thermionic Experiments with a New Source of Positive.

PMID- 16587129
TI  - The Dielectric Constant and Diamagnetism of Hydrogen and Helium in the New
      Quantum Mechanics.

PMID- 16587130
TI  - On the Equilibrium between Radiation and Matter.

PMID- 16587131
TI  - Extension of Doublet Laws in the First Long Period to chromium and Manganese.

PMID- 16587132
TI  - Ionic Mobilities in Ammonia-Hydrogen Mixtures and an Anomalous Effect of Ammonia.

PMID- 16587133
TI  - Note on the Correspondence Principle in the New Quantum Theory.

PMID- 16587135
TI  - Genetic Evidence of a Selective Segregation of Chromosomes in Sciara (Diptera).

PMID- 16587134
TI  - Miniature-alpha-A Second Frequently Mutating Character in Drosophila Virilis.

PMID- 16587136
TI  - Decomposition of Ammonia by Optically Excited Mercury Atoms.

PMID- 16587137
TI  - The Concentration and Identification of the Element of Atomic Number 61.

PMID- 16587138
TI  - The Density of Oxygen and Its Compressibility below One Atmosphere: II.

PMID- 16587139
TI  - The Density, Compressibility and Atomic Weight of Nitrogen.

PMID- 16587141
TI  - Photosensitized Decompositions by Excited Mercury Atoms.

PMID- 16587140
TI  - The Synthesis and Disintegration of Atoms as Revealed by the Photography of
      Wilson Cloud Tracks.

PMID- 16587142
TI  - Some Applications of the Ionization Formula.

PMID- 16587143
TI  - On the Spectra of Stars of Class c F8.

PMID- 16587144
TI  - The Apparition Dates of the Andromede (or Bielid) Meteor Swarms.

PMID- 16587145
TI  - Larval Stages in a Protozoon.

PMID- 16587146
TI  - Transformations of Manifolds with a Boundary.

PMID- 16587147
TI  - A Possible Way to Discuss the Fundamental Principles of Relativity.

PMID- 16587148
TI  - Concerning Paths That Do Not Separate a Given Continuous Curve.

PMID- 16587149
TI  - On Simply Transitive Primitive Groups.

PMID- 16587150
TI  - Quadractic Forms Which Represent All Integers.

PMID- 16587152
TI  - Concerning Certain Types of Continuous Curves.

PMID- 16587151
TI  - Congruences of Parallelism of a Field of Vectors.

PMID- 16587153
TI  - Summary of Results and Proofs Concerning Fermat's Last Theorem (Second Note).

PMID- 16587154
TI  - Absorption Bands in Nitrogen.

PMID- 16587155
TI  - Action of Radiation and Perturbations on Atoms.

PMID- 16587156
TI  - The Periodicity of Photoelectric Thresholds.

PMID- 16587157
TI  - Microsporogenesis in the Cucumber.

PMID- 16587158
TI  - Further Studies on Biochemical Differences between Sexes in Plants.

PMID- 16587159
TI  - Inheritance of Trimorphism in Lythrum Salicaria.

PMID- 16587160
TI  - The Fasting of Large Ruminants.

PMID- 16587161
TI  - The Basal Metabolism of Steers.

PMID- 16587162
TI  - The Metabolic Stimulus of Food in the Case of Steers.

PMID- 16587163
TI  - Studies on the Effect of Potassium Alum-Hydrochloric Acid Solutions on the Growth
      and Fate of Neoplastic Tissue: 1. Effect on a Slow-Growing Adeno-Carcinoma of the
      Mouse.

PMID- 16587164
TI  - Dynamical Economics.

PMID- 16587165
TI  - On the Proof of Sheppard's Corrections.

PMID- 16587166
TI  - Note on a Generalization of Taylor's Series.

PMID- 16587167
TI  - A Theory of Matter and Electricity.

PMID- 16587169
TI  - Groups Generated by Two Operators of Order Three Whose Product Is of Order Six.

PMID- 16587168
TI  - The Hydrogen Atom and the Balmer Formula.

PMID- 16587170
TI  - Pinhole Probe Experiments with Massive Air Columns.

PMID- 16587171
TI  - The Fine Structure of the Helium Arc Spectrum.

PMID- 16587172
TI  - Two Remarks on Schrodinger's Quantum Theory.

PMID- 16587173
TI  - On King's Classical Theory of Radiation.

PMID- 16587174
TI  - Mineralogical Content of Maine Sands in Relation to Mortar Strength.

PMID- 16587175
TI  - On the Mechanics of Blood Flow, with Special Reference to the Influence of Change
      of Posture.

PMID- 16587176
TI  - The Nature of the Insensible Perspiration.

PMID- 16587177
TI  - Hermaphroditism in a Dioicous Hepatic.

PMID- 16587178
TI  - Modifications of Nerve Centers Due to the Transplantation of the Eye and
      Olfactory Organ in Anuran Embryos.

PMID- 16587179
TI  - On the Growth, Care and Behavior of Loggerhead Turtles in Captivity.

PMID- 16587180
TI  - Magnetic Hydrogen Atoms and Non-Magnetic Molecules.

PMID- 16587181
TI  - The Relation of the Octet of Electrons to Ionization.

PMID- 16587183
TI  - On the Distance of the Sun from the Galactic Plane.

PMID- 16587182
TI  - Ultra-Violet Solar Radiation.

PMID- 16587184
TI  - The Relationship of Spectral Type to Period among Variable Stars.

PMID- 16587185
TI  - High Dispersion Stellar Spectra and Some Results of a Study of gamma Cygni.

PMID- 16587186
TI  - Groups of Collineations in a Space of Paths.

PMID- 16587187
TI  - Remarks on the Quantum Theory of Diffraction.

PMID- 16587188
TI  - Absolute Intensities in the Hydrogen-Chloride Rotation Spectrum.

PMID- 16587189
TI  - Note on "Pendulum" Orbits in Atomic Models.

PMID- 16587190
TI  - Measurement of the Mo.K Doublet Distances by Means of the Double X-Ray
      Spectrometer.

PMID- 16587191
TI  - The Structure of the Helium Atom: I.

PMID- 16587192
TI  - The Zeeman Effect of the Hyper-Fine Structure Components of lambda 2537 of
      Mercury.

PMID- 16587193
TI  - The Dielectric Constant of Atomic Hydrogen in Undulatory Mechanics.

PMID- 16587194
TI  - The Dielectric Constant of Atomic Hydrogen from the Point of View of Bohr's
      Quantum Theory.

PMID- 16587196
TI  - Mucronate Electrode with Micrometer.

PMID- 16587195
TI  - Direct and Indirect Production of Characteristic X-Rays.

PMID- 16587197
TI  - The Reflection of Electrons from Crystals.

PMID- 16587198
TI  - Coupling of Electronic and Nuclear Motions in Diatomic Molecules.

PMID- 16587200
TI  - A New Equation for the Distribution of Radiant Energy.

PMID- 16587199
TI  - Wave Mechanics and the Normal State of the Hydrogen Molecule.

PMID- 16587201
TI  - The Hydrogen Atom with a Spinning Electron in Wave Mechanics.

PMID- 16587202
TI  - Additional Evidence as to the Intercellular Formation of Connective Tissue.

PMID- 16587204
TI  - Vision and Retinal Structure in Mice.

PMID- 16587203
TI  - Results of Heteroplastic Transplantations of the Heart Rudiment in Amblystoma
      Embryos.

PMID- 16587205
TI  - Zeeman Effect and Structure in the Spark Spectra of Tin.

PMID- 16587206
TI  - The Structure of Certain Bands in the Visible Spectrum of Boron Monoxide.

PMID- 16587207
TI  - Pressure Phenomena of the Mucronate Anode.

PMID- 16587208
TI  - On the Lag of the Kerr Effect.

PMID- 16587209
TI  - Mobilities of Ions in Acetylene Hydrogen Mixtures.

PMID- 16587210
TI  - Current Distribution in Supraconductors.

PMID- 16587211
TI  - On the Reflection of Electrons from Crystal Lattices.

PMID- 16587212
TI  - Displacement of Certain Multiplets and Multiple Levels for Elements in the First
      Long Period.

PMID- 16587213
TI  - Energy Relationships and Ionization Potentials of Atoms of the First Row of the
      Periodic Table in All Stages of Ionization.

PMID- 16587214
TI  - Polarization of Light Reflected from Rough Surfaces with Special Reference to
      Light Reflected by the Moon.

PMID- 16587216
TI  - The Uni-Molecular Decomposition of Azo-Methane; the Adequacy of Activation by
      Collision.

PMID- 16587215
TI  - The Trails of Two Periodically Flickering Meteors.

PMID- 16587217
TI  - On X-Ray Diffraction Patterns from Liquids and Colloidal Gels.

PMID- 16587218
TI  - The Effect of Tubercle Bacilli and the Chemical Fractions Obtained from Analysis
      on the Cells of the Connective Tissues in Rabbits.

PMID- 16587219
TI  - The Embryology of Equisetum Debile Roxb.

PMID- 16587221
TI  - The Architectural Evolution of Pueblo Bonito.

PMID- 16587222
TI  - A New Genus of Brazilian Characin Fishes Allied to Bivibranchia.

PMID- 16587220
TI  - The Effect of Small Amounts of Chemicals in Increasing the Life Activities of
      Plants.

PMID- 16587223
TI  - Nervous Control of Xanthophore Changes in Fundulus.

PMID- 16587224
TI  - A Quantitative Basis for the Relation between Visual Acuity and Illumination.

PMID- 16587226
TI  - Linkage of Short Ear and Density in the House Mouse.

PMID- 16587225
TI  - The Flora of the Hermit Shale in the Grand Canyon, Arizona.

PMID- 16587227
TI  - Note on Corrections to H. A. Newton's "1850 Dates" of Meteor Showers.

PMID- 16587229
TI  - Explanation of the Incomplete Polarization of Mercury Resonance Radiation.

PMID- 16587228
TI  - Reciprocating Acoustic Vibration on Opposite Sides of the Pinhole, in Long Quill
      Tubes.

PMID- 16587230
TI  - The Space-Distribution of the Photo-Electrons Ejected by X-Rays.

PMID- 16587231
TI  - Surface Tension of Molten Metals: I. Copper.

PMID- 16587232
TI  - The Relation between Temperature and Work Function in Thermionic Emission.

PMID- 16587233
TI  - On the Spectrum of Argon in the Extreme Ultra-Violet.

PMID- 16587234
TI  - A Redetermination of the Newtonian Constant of Gravitation.

PMID- 16587235
TI  - Contact Transformations of Three-Space Which Convert a System of Paths into a
      System of Paths.

PMID- 16587237
TI  - Felix Klein and the History of Modern Mathematics.

PMID- 16587236
TI  - Motion and Collineations in General Space.

PMID- 16587238
TI  - The Residual Set of a Complex on a Manifold and Related Questions.

PMID- 16587239
TI  - A Disproof of the Radiation Theory of Chemical Activation.

PMID- 16587240
TI  - Radiation and Collision in Gaseous Chemical Reactions.

PMID- 16587241
TI  - Note on a Correction Formula for Artificially Deformed Crania.

PMID- 16587242
TI  - The Interrelation of the Eyes of Palaemonetes as Concerns Retinal Pigment
      Migration.

PMID- 16587243
TI  - The Blood-Vessels of Annelids.

PMID- 16587245
TI  - Remark on a Theorem of R. L. Moore.

PMID- 16587244
TI  - The Effect of a Rotation of the Galaxy on Proper Motions in Right Ascension and
      Declination.

PMID- 16587246
TI  - Concerning the Open Subsets of a Plane Continuous Curve.

PMID- 16587247
TI  - On the Functional Independence of Ratios of Theta Functions.

PMID- 16587248
TI  - The Direction of Ejection of X-Ray Electrons.

PMID- 16587249
TI  - The Character of the General or Continuous Spectrum Radiation.

PMID- 16587250
TI  - The Structure of the Atmospheric Absorption Bands of Oxygen.

PMID- 16587251
TI  - Revision of Rowland's Preliminary Tables of Solar Spectrum Wave-Lengths.

PMID- 16587252
TI  - Application of the Law of Similitude to Hydraulic Laboratory Research.

PMID- 16587254
TI  - The Application of Experimental Methods to the Study of Developing Fundulus
      Embryos.

PMID- 16587253
TI  - Some Factors Influencing the Ignition of Carbon Monoxide and Oxygen.

PMID- 16587255
TI  - The Action of Na, K and Ca Chlorides on the Egg of Fundulus.

PMID- 16587256
TI  - Absorption of Ultra-Sonic Waves by Hydrogen and Carbon Dioxide.

PMID- 16587257
TI  - On the Fine Structure of Some Mercury Lines.

PMID- 16587258
TI  - On the Duration of the Existence of Doubly Charged Positive Ions in Gases, and
      Their Detection.

PMID- 16587259
TI  - Groups Generated by Two Operators of Order Three, the Cube of Whose Product is
      Invariant.

PMID- 16587260
TI  - Some Separation Theorems.

PMID- 16587261
TI  - A Working Hypothesis for Segmental Interchange between Homologous Chromosomes.

PMID- 16587262
TI  - The Heterogeneous Thermal Decomposition of Ammonia in Strong Electric Fields.

PMID- 16587263
TI  - The Photochemical Decomposition of Hydrogen-Iodide; the Mode of Optical
      Dissociation.

PMID- 16587264
TI  - The Detection of Uranium by a Photoluminescence Test.

PMID- 16587265
TI  - Cancer Studies in Massachusetts: 1. The Relationship between Cancer and Density
      of Population in Massachusetts.

PMID- 16587266
TI  - A Periodic Table of the Structure of Atoms and Its Relation to Ion-Formation and
      Valence.

PMID- 16587268
TI  - General Arithmetic.

PMID- 16587267
TI  - The Magnetic Behavior of Ozone.

PMID- 16587269
TI  - On the Structure of a Plane Continuous Curve.

PMID- 16587270
TI  - On the Arithmetic of Abelina Functions.

PMID- 16587271
TI  - Groups Whose Operators Are of the Form st.

PMID- 16587272
TI  - The Continuous Spectrum of Hydrogen.

PMID- 16587273
TI  - The Impulse Moment of the Light Quantum.

PMID- 16587274
TI  - The Symmetry of the Stress-Tensor Obtained by Schroedinger's Rule.

PMID- 16587276
TI  - X-Ray Diffraction in Liquids: Saturated Normal Fatty Acids. Isomers of Primary
      Normal Alcohols and Normal Paraffins.

PMID- 16587275
TI  - Some Extensions of Theory and Measurements of Shot-Effect in Periodic Circuits.

PMID- 16587277
TI  - The Structure and Dimensions of the Benzene Ring.

PMID- 16587278
TI  - The Space Group of Potassium, Rubidium and Caesium Sulphates.

PMID- 16587279
TI  - The Diamagnetic Susceptibility of Hydrogen Molecule and of Helium in the New
      Quantum Mechanics.

PMID- 16587280
TI  - On the Quantum Theory of the Polarization of Impact Radiation.

PMID- 16587281
TI  - The Residual Set of a Complex on a Manifold and Related Questions (Second Note).

PMID- 16587282
TI  - Power Series Expansions in the Neighborhood of a Point on a Surface.

PMID- 16587283
TI  - The Analysis and Analysis Situs of Regular n-Spreads in (n + r)-Space.

PMID- 16587284
TI  - On Certain Properties of Frequency Distributions of the Powers and Roots of the
      Variates of a Given Distribution.

PMID- 16587285
TI  - The Penetration of Methylene Blue into Living Cells.

PMID- 16587287
TI  - The Influence of a Power Dam in Modifying Conditions Affecting the Migration of
      the Salmon.

PMID- 16587286
TI  - Studies on the Effect of Potassium Alum-Hydrochloric Acid Solutions on the Growth
      and Fate of Neoplastic Tissue: II. Result Obtained on a Rapidly Growing
      Transplantable Sarcoma of the Mouse.

PMID- 16587288
TI  - A Note on the Triple System, lambda Tauri.

PMID- 16587289
TI  - Quantitative Aspects of Tonic Immobility in Vertebrates.

PMID- 16587290
TI  - Sensori-Motor Consequences of Passive Rotary and Rectilinear Oscillation of the
      Body.

PMID- 16587291
TI  - Foster Parent-Foster Child Comparisons as Evidence upon the Nature-Nurture
      Problem.

PMID- 16587292
TI  - The Thermal and Photochemical Decomposition of Azo Compounds and the Problem of
      Reaction Rates.

PMID- 16587293
TI  - The Growth of Seedlings of the Canteloup, Cucumis Melo, in the Absence of
      Exogenous Food and Light.

PMID- 16587294
TI  - The Photochemical Union of Hydrogen and Chlorine.

PMID- 16587295
TI  - The Quantum Levels and Resulting Constants of the Hydrogen Molecule.

PMID- 16587296
TI  - The Scattering of X-Rays from Gases.

PMID- 16587297
TI  - The Distribution of Energy in Molecules.

PMID- 16587298
TI  - The Life of Atomic States and the Intensity of Spectral Lines.

PMID- 16587299
TI  - THE SPECTRA OF SINGLY AND DOUBLY IONIZED GERMANIUM (GE II AND III).

PMID- 16587300
TI  - The Structure and Dimensions of the Ethane Molecule.

PMID- 16587301
TI  - The Lattice Structure of Ethane.

PMID- 16587302
TI  - Relations of Field-Currents to Thermionic-Currents.

PMID- 16587303
TI  - Some Factors in Rock Metamorphism.

PMID- 16587304
TI  - The Density, Compressibility and Atomic Weight of Neon.

PMID- 16587305
TI  - The Density, Compressibility and Atomic Weight of Argon.

PMID- 16587306
TI  - The Chromosomes of Pellia Neesiana.

PMID- 16587307
TI  - The Production of Variation in Nicotiana Species by X-Ray Treatment of Sex Cells.

PMID- 16587308
TI  - Genetic Effects of X-Rays in Maize.

PMID- 16587310
TI  - General Theory of Polygenic or Non-Monogenic Functions: The Derivative Congruence
      of Circles.

PMID- 16587309
TI  - Late Tertiary Thrust Faults in the Mojave Desert, California.

PMID- 16587311
TI  - Number of Systems of Imprimitivity of Transitive Substitution Groups.

PMID- 16587312
TI  - Concerning Triods in the Plane and the Junction Points of Plane Continua.

PMID- 16587313
TI  - On Methods and Applications in Spectrophotometry.

PMID- 16587314
TI  - The Effect of Posture upon the Composition and Volume of the Blood in Man.

PMID- 16587315
TI  - Sterility in American Marriages.

PMID- 16587316
TI  - On the Separation of Points of a Continuous Curve by Arcs and Simple Closed
      Curves.

PMID- 16587317
TI  - On Some Properties of One-Valued Transformations of Manifolds.

PMID- 16587318
TI  - Harmony as a Principle of Mathematical Development.

PMID- 16587319
TI  - Note on the Behavior of Certain Power Series on the Circle of Convergence with
      Application to a Problem of Carleman.

PMID- 16587320
TI  - Intra-Seasonal Cycles of Growth.

PMID- 16587321
TI  - Studies on the Biochemical Differences between Sexes in Mucors: 4. Enzymes Which
      Act upon Carbohydrates and Their Derivatives.

PMID- 16587322
TI  - Induced Immunity in Plants.

PMID- 16587323
TI  - On the Binocular Fusion of Colors and Its Relation to Theories of Color Vision.

PMID- 16587325
TI  - Artificial Production of Janus Embryos of Chaetopterus.

PMID- 16587324
TI  - On the Motion of the Magellanic Clouds.

PMID- 16587326
TI  - Anode and Cathode Sparks Differentiated by the Mucronate Electrode.

PMID- 16587327
TI  - A Spectroscopic Criterion for the Benzenoid Structure in Some Types of
      Triphenylmethane Derivatives.

PMID- 16587328
TI  - The Dispersion by Hydrogen-Like Atoms in Undulatory Mechanics.

PMID- 16587329
TI  - The Production of Active Nitrogen.

PMID- 16587330
TI  - On the Quantum Theory of the Ramsauer Effect.

PMID- 16587331
TI  - The Fifth Dimension in Relativistic Quantum Theory.

PMID- 16587332
TI  - On the Extension of Thermodynamics to General Relativity.

PMID- 16587333
TI  - On the Variation of the Electromotive Force in a Photoactive Cell, Containing a
      Fluorescent Electrolyte, with the Intensity of Illumination.

PMID- 16587334
TI  - A Note on Corona at High Humidity.

PMID- 16587335
TI  - The Spark Spectrum of Neon.

PMID- 16587336
TI  - On Hierarchical Correlation Systems.

PMID- 16587338
TI  - On the Distortion of the Continuous Background by Wide Absorption Lines.

PMID- 16587337
TI  - Dynamic Relations between Plant and Soil, with Special Reference to the Supply of
      Water and Oxygen.

PMID- 16587339
TI  - A Case of Streaming in a Valve.

PMID- 16587340
TI  - Studies on Biochemical Differences between Sexes in Mucors: 5. Quantitative
      Determinations of Sugars in (+) and (-) Races.

PMID- 16587341
TI  - Reflection of Electrons by a Crystal of Nickel.

PMID- 16587342
TI  - The Limits of Accuracy in Physical Measurements.

PMID- 16587344
TI  - Direct and Indirect Characteristic X-Rays: Their Ratio as a Function of Cathode
      Ray Energy.

PMID- 16587343
TI  - A Critical Experiment on the Statistical Interpretation of Quantum Mechanics.

PMID- 16587345
TI  - K-Electron Ionization by Direct Impact of Cathode Rays.

PMID- 16587346
TI  - Analysis of Spectra Arising from Quadruply Ionized Tin, Sn V.

PMID- 16587347
TI  - On the Energy and Entropy of Einstein's Closed Universe.

PMID- 16587348
TI  - On the Equilibrium between Radiation and Matter in Einstein's Closed Universe.

PMID- 16587350
TI  - The Shared-Electron Chemical Bond.

PMID- 16587349
TI  - Photochemical Ozonization and Its Relation to the Polymerization of Oxygen.

PMID- 16587351
TI  - A Stratification of Remains at an Early Maya Site.

PMID- 16587352
TI  - The Degree of Association of Sodium Vapor.

PMID- 16587353
TI  - The Interrelation between Diatoms, Their Chemical Environment, and Upwelling
      Water in the Sea, Off the Coast of Southern California.

PMID- 16587354
TI  - Transformation of Conjugate Elements or of Conjugate Subgroups.

PMID- 16587355
TI  - Observations upon Complement Fixation in Infections with Endamoeba Histolytica.

PMID- 16587356
TI  - Reversible Crystallization in Tendons and Its Functional Significance.

PMID- 16587357
TI  - An Interpretation of Excitation, Exhaustion and Death in Terms of Physical
      Constants.

PMID- 16587358
TI  - The Polarization of Characteristic Radiation.

PMID- 16587359
TI  - The Repulsion between Electric Currents and Their Induced Eddy Currents in
      Parallel.

PMID- 16587360
TI  - Apparent Evidence of Polarization in a Beam of beta-Rays.

PMID- 16587361
TI  - The Spectrum and State of Polarization of Fluorescent X-Rays.

PMID- 16587362
TI  - An Interpretation of Dirac's Theory of the Electron.

PMID- 16587364
TI  - Angular Scattering of Electrons in Hydrogen and Helium.

PMID- 16587363
TI  - Regularities Exhibited between Certain Multiplets for Elements in the Second Long
      Period.

PMID- 16587365
TI  - Thermodynamics Based on Statistics: I.

PMID- 16587366
TI  - Thermodynamics Based on Statistics: II.

PMID- 16587367
TI  - A Proposed Experiment on the Nature of Light.

PMID- 16587368
TI  - The Spectrum of X-Rays from the Back of a Tungsten Target.

PMID- 16587369
TI  - Absolute X-Ray Wave-Length Measurements.

PMID- 16587370
TI  - On the Thermodynamic Equilibrium in the Universe.

PMID- 16587371
TI  - Algal Deposits of Unkar Proterozoic Age in the Grand Canyon, Arizona.

PMID- 16587372
TI  - The Thermal Decomposition of Ammonia upon Mixed Surfaces of Tungsten and
      Platinum.

PMID- 16587373
TI  - The Crystal Structure of Topaz.

PMID- 16587374
TI  - The Intensive Drying of Liquids.

PMID- 16587375
TI  - A Progression Relation in the Molecular Spectrum of Oxygen Occurring in the
      Liquid and in the Gas at High Pressure.

PMID- 16587377
TI  - The Crystal Structures of the Alkaline Earth Metals.

PMID- 16587376
TI  - The Heat of Dissociation of Oxygen as Estimated from Photochemical Ozonization.

PMID- 16587378
TI  - Reflection and Refraction of Electrons by a Crystal of Nickel.

PMID- 16587379
TI  - Oscillations in Ionized Gases.

PMID- 16587380
TI  - Evidence That the Cosmic Rays Originate in Interstellar Space.

PMID- 16587381
TI  - The Displacement Interferometry of Barometric Pressure.

PMID- 16587382
TI  - The Structure of Acetylene.

PMID- 16587384
TI  - Radiation and Relativity: II.

PMID- 16587383
TI  - On Derivatives of Non-Analytic Functions.

PMID- 16587385
TI  - Concerning Plane Closed Point Sets Which Are Accessible from Certain Subsets of
      Their Complements.

PMID- 16587386
TI  - Incomplete Systems of Partial Differential Equations.

PMID- 16587387
TI  - The Effect of Temperature on the Viability of Superfemales in Drosophila
      Melanogaster.

PMID- 16587388
TI  - Preliminary Note on the Elastic Hysteresis of the Human Aorta.

PMID- 16587389
TI  - Intensities of K-Series X-Rays from Thin Targets.

PMID- 16587390
TI  - The Spectrum of the Hydrogen Molecular Ion.

PMID- 16587391
TI  - The Absorption Spectrum of Nitrogen Dioxide.

PMID- 16587392
TI  - The Relation of Hydrolysis to the Validity of Beer's Law.

PMID- 16587393
TI  - Further Remarks on the Second Law of Thermodynamics in General Relativity.

PMID- 16587395
TI  - The Hypostase: Its Presence and Function in the Ovule of the Onagraceae.

PMID- 16587394
TI  - Series Spectra of Cadmium-Like Atoms.

PMID- 16587396
TI  - Glycogen as a Means of Ciliary Reversal.

PMID- 16587397
TI  - The Production of Mutations by X-Rays.

PMID- 16587398
TI  - On the Roots of the Derivative of a Polynomial.

PMID- 16587399
TI  - Concerning the [unk] Group of Transformations.

PMID- 16587400
TI  - Conformal Tensors and Connections.

PMID- 16587401
TI  - The Group Manifold of Finite Continuous Point and Functional Transformation
      Groups.

PMID- 16587402
TI  - Is It Possible to Test by a Direct Experiment the Hypothesis of the Spinning
      Electron?

PMID- 16587403
TI  - On the Distribution Law in Locally Rapidly Fluctuating Fields Which Are Steady
      When Averaged over a Sufficient Time Interval.

PMID- 16587404
TI  - The Crystal Structure of Potassium Sulphate.

PMID- 16587405
TI  - Further Experiments in Microbarometry.

PMID- 16587406
TI  - Reflection of Soft X-Rays.

PMID- 16587407
TI  - Fluorescence and Solid Solution.

PMID- 16587409
TI  - Systematic Variations of the Constant A in Thermionic Emission.

PMID- 16587408
TI  - Note on the Lyman Bands of Hydrogen.

PMID- 16587410
TI  - The Photoelectric Long Wave Limit of Potassium Vapor.

PMID- 16587411
TI  - Emergent Energy of Photoelectrons in Potassium Vapor.

PMID- 16587412
TI  - Electric Conductivity and Optical Absorption of Metals.

PMID- 16587414
TI  - A Fifth Allelomorph in the Agouti Series of the House Mouse.

PMID- 16587413
TI  - A Description of the Ontogenetic Development of Retinal Action Currents in the
      House Mouse.

PMID- 16587415
TI  - Determination of All the Groups Which Contain a Given Group as an Invariant
      Subgroup of Prime Index.

PMID- 16587416
TI  - Color Changes in Excised Pieces of the Integument of Anolis Equestris under the
      Influence of Light.

PMID- 16587417
TI  - The Form of the Growth Curve of the Canteloup (Cucumis Melo) under Field
      Conditions.

PMID- 16587418
TI  - Invariant Sequences.

PMID- 16587419
TI  - Normal Division Algebras Satisfying Mild Assumptions.

PMID- 16587420
TI  - The Group of the Rank Equation of Any Normal Division Algebra.

PMID- 16587421
TI  - Postulates for an Abstract Arithmetic.

PMID- 16587422
TI  - On the Characteristic Values of Linear Integral Equations.

PMID- 16587423
TI  - On the Summability of Fourier Series.

PMID- 16587424
TI  - Groups Involving a Cyclic, a Dicyclic, or a Dihedral Group as an Invariant
      Subgroup of Prime Index.

PMID- 16587425
TI  - The Weight-Length Relation in Fishes.

PMID- 16587426
TI  - A Cross-over between the Genes for Short-Ear and Density in the House Mouse.

PMID- 16587427
TI  - Evidence that the Female Is Responsible for the Sex Ratio in Sciara (Diptera).

PMID- 16587428
TI  - Observations on Sex-Ratio Determination in Sciara (Diptera).

PMID- 16587429
TI  - The Relation between Polarization and Association.

PMID- 16587430
TI  - pH Measurement with the Glass Electrode and Vacuum Tube Potentiometer.

PMID- 16587431
TI  - Chemical Reaction in the Interferometer U-Gauge.

PMID- 16587432
TI  - Resistance and Thermo-Electric Phenomena in Metal Crystals.

PMID- 16587433
TI  - Angular Distribution of Intensity of Resonance Radiation.

PMID- 16587434
TI  - Some Multiplets of Singly Ionized Thallium.

PMID- 16587435
TI  - The Influence of the Presence of Hydrogen on the L(111) X-ray Absorption Edge of
      Palladium.

PMID- 16587436
TI  - Studies of the Galactic Center: III. The Absolute Magnitudes of Long Period
      Variables.

PMID- 16587437
TI  - The Absolute Magnitudes of Long Period Variable Stars.

PMID- 16587438
TI  - THE CRYSTAL STRUCTURE OF ANHYDROUS SILICOTUNGSTIC ACID AND RELATED COMPOUNDS AND
      THEIR PROBABLE MOLECULAR FORMULAS.

PMID- 16587439
TI  - A NEW EQUATION OF STATE.

PMID- 16587440
TI  - THE EFFECT OF DIFFUSION AT A MOVING BOUNDARY BETWEEN TWO SOLUTIONS OF
      ELECTROLYTES.

PMID- 16587441
TI  - ADIABATIC EXPANSION IN CASE OF VANISHING INCREMENTS.

PMID- 16587442
TI  - THE CONDITION OF SELF-OSCILLATION OF A GENERAL TRIODE SYSTEM.

PMID- 16587443
TI  - ON THE SYMMETRY OF PROTONIC WAVE FUNCTIONS.

PMID- 16587444
TI  - POSITIVE ION CURRENTS IN THE POSITIVE COLUMN OF THE GLOW-DISCHARGE IN THE NOBLE
      GASES.

PMID- 16587445
TI  - NOTE ON THE D LINE EXCITATION BY THE GREEN SODIUM BAND AND THE DISSOCIATION
      POTENTIAL OF SODIUM VAPOR.

PMID- 16587446
TI  - ON THE SUMMABILITY OF FOURIER SERIES. SECOND NOTE.

PMID- 16587447
TI  - SUMMARY OF RESULTS AND PROOF CONCERNING FERMAT'S LAST THEOREM (THIRD PAPER).

PMID- 16587448
TI  - THE DIRECT EFFECT OF TEMPERATURE CHANGES UPON THE MELANOPHORES OF THE LIZARD
      ANOLIS EQUESTRIS.

PMID- 16587449
TI  - FURTHER STUDIES ON THE INFLUENCE OF A POWER DAM IN MODIFYING CONDITIONS AFFECTING
      THE MIGRATION OF THE SALMON.

PMID- 16587450
TI  - PHARMACOLOGICAL SYNERGISM OF STEREOISOMERS.

PMID- 16587451
TI  - BINARY SOLUTIONS OF CONSOLUTE LIQUIDS.

PMID- 16587452
TI  - POTENTIALS OF GENERAL MASSES IN SINGLE AND DOUBLE LAYERS. THE RELATIVE BOUNDARY
      VALUE PROBLEMS.

PMID- 16587453
TI  - SUMMARY OF RESULTS AND PROOFS ON FERMAT'S LAST THEOREM (FOURTH PAPER).

PMID- 16587454
TI  - THE ANALYSIS OF A CONCRETE CASE OF INTERGRADATION BETWEEN TWO SUBSPECIES.

PMID- 16587455
TI  - NOTE ON C. S. PEIRCE'S EXPERIMENTAL DISCUSSION OF THE LAW OF ERRORS.

PMID- 16587456
TI  - PHOTO-ELECTRIC EMISSION AND THERMIONIC EMISSION ONCE MORE.

PMID- 16587457
TI  - THE QUANTUM LAWS AND THE UNCERTAINTY PRINCIPLE OF HEISENBERG.

PMID- 16587458
TI  - THE TRANSFORMATION SPECTRUM OF THE RUBY.

PMID- 16587459
TI  - THE EFFECTS OF AN HOMOLOGOUS SERIES OF AMINES ON THE MOBILITIES OF IONS IN
      HYDROGEN GAS.

PMID- 16587460
TI  - LATE GEOLOGIC DEFORMATION OF THE APPALACHIAN PIEDMONT AS DETERMINED BY RIVER
      GRAVELS.

PMID- 16587461
TI  - CONTROL OF SEX IN CLADOCERA. III. LOCALIZATION OF THE CRITICAL PERIOD FOR CONTROL
      OF SEX.

PMID- 16587462
TI  - GENETIC IDENTIFICATION OF THE SEX CHROMOSOMES IN SCIARA (DIPTERA).

PMID- 16587464
TI  - POSSIBLE alpha-AUTOMORPHISMS OF NON-ABELIAN GROUPS.

PMID- 16587463
TI  - A SPONTANEOUS MUTATION IN THE HOUSE MOUSE.

PMID- 16587465
TI  - ON CONTINUOUS CURVES HAVING CERTAIN PROPERTIES.

PMID- 16587466
TI  - ON SIMPLE CLOSED CURVES AND OPEN CURVES.

PMID- 16587467
TI  - ON A RELATION BETWEEN CONFORMAL AND PROJECTIVE GROUPS IN FUNCTION SPACE.

PMID- 16587469
TI  - ON THE POSSIBLE LINE ELEMENTS FOR THE UNIVERSE.

PMID- 16587468
TI  - ON ELEMENTS OF CONTENT IN METRICAL GEOMETRY.

PMID- 16587470
TI  - THE EXISTENCE OF RADIOACTIVE RECOIL IONS OF HIGH MOBILITY.

PMID- 16587471
TI  - AN INTENSITY GAUGE FOR "SUPERSONIC" RADIATION IN LIQUIDS.

PMID- 16587472
TI  - HYDROGEN-ION WAVE FUNCTION.

PMID- 16587473
TI  - LATENT CARRIERS OF ELECTRICITY IN THE GASEOUS DISCHARGE.

PMID- 16587474
TI  - GRAVITATION AND THE ELECTRON.

PMID- 16587475
TI  - RAMAN SPECTRA OF SOLUTIONS OF SOME IONIZED SUBSTANCES.

PMID- 16587477
TI  - SELECTIVE SEGREGATION OF CHROMOSOMES IN MALES OF A THIRD SPECIES OF SCIARA.

PMID- 16587476
TI  - THE CRYSTAL STRUCTURE OF STRONTIUM.

PMID- 16587478
TI  - THE OCCURRENCE OF CHROMOSOME VARIANTS IN NICOTIANA ALATA LK. ET OTTO.

PMID- 16587479
TI  - AN EOGENE TROPICAL FOREST IN THE PERUVIAN DESERT.

PMID- 16587481
TI  - ON THE SPHERICALLY SYMMETRICAL STATICAL FIELD IN EINSTEIN'S UNIFIED THEORY OF
      ELECTRICITY AND GRAVITATIONS.

PMID- 16587480
TI  - ON THE STABILITY OF GASEOUS STELLAR STRUCTURES.

PMID- 16587482
TI  - UNIMOLECULAR REACTIONS.

PMID- 16587483
TI  - A GENERALIZATION OF ROLLE'S THEOREM WITH APPLICATION TO ENTIRE FUNCTIONS.

PMID- 16587484
TI  - DUALITY RELATIONS IN TOPOLOGY.

PMID- 16587485
TI  - GROUPS WHICH ADMIT THREE-FOURTHS AUTOMORPHISMS.

PMID- 16587486
TI  - THE RANK FUNCTION OF ANY SIMPLE ALGEBRA.

PMID- 16587487
TI  - CONFORMAL GEOMETRY OF GENERALIZED METRIC SPACES.

PMID- 16587488
TI  - THE MEAN SQUARE ANGULAR MOMENTUM AND DIAMAGNETISM OF THE NORMAL HYDROGEN
      MOLECULE.

PMID- 16587489
TI  - EFFECTS OF A CRYSTALLOGRAPHIC TRANSFORMATION ON THE PHOTOELECTRIC AND THERMIONIC
      EMISSION FROM COBALT.

PMID- 16587490
TI  - THE REFLECTING POWER OF SOME SUBSTANCES IN THE EXTREME ULTRA-VIOLET.

PMID- 16587491
TI  - THE PROBLEM OF THE IONIZED HYDROGEN MOLECULE.

PMID- 16587492
TI  - NOTE ON THE VELOCITIES AND MAGNITUDES OF EXTERNAL GALAXIES.

PMID- 16587493
TI  - WATER-INTAKE AND ITS RELATION TO THE SURFACE AREA OF THE BODY.

PMID- 16587494
TI  - THE INFLUENCE OF THYROID GLAND FEEDING ON THE ACCELERATION OF THE GROWTH OF
      LARVAE OF DROSOPHILA MELANOGASTER.

PMID- 16587495
TI  - ON THE GEOTROPIC RESPONSE IN YOUNG RATS.

PMID- 16587497
TI  - THE TEMPERATURE COEFFICIENT OF RADIOACTIVE DISINTEGRATION.

PMID- 16587496
TI  - DIELECTRIC LOSS IN ELECTROLYTE SOLUTIONS IN HIGH FREQUENCY.

PMID- 16587498
TI  - SOME STUDIES ON HOMOGENEOUS CATALYSIS.

PMID- 16587499
TI  - UNIMOLECULAR REACTIONS.

PMID- 16587500
TI  - THE ROCK SUITES OF THE PACIFIC AND THE ATLANTIC BASINS.

PMID- 16587501
TI  - A METHOD FOR THE DETERMINATION OF THE ACTIVITY OF ANTIPOLIOMYELITIC SERUM.

PMID- 16587502
TI  - THE CHROMOSOMES OF SOME DIOECIOUS ANGIOSPERMS.

PMID- 16587503
TI  - CHARACTERIZATION OF CONTINUOUS CURVES THAT ARE PERFECTLY CONTINUOUS.

PMID- 16587504
TI  - DOES NATURAL IONIZING RADIATION CONTROL RATE OF MUTATION?

PMID- 16587505
TI  - CHEMICAL INVESTIGATION OF BIOLOGICALLY ACTIVE LIPOIDS OF TUBERCLE BACILLI.

PMID- 16587506
TI  - A HOMOZYGOUS TRANSLOCATION IN DROSOPHILA MELANOGASTER.

PMID- 16587507
TI  - MAGNETIC SUSCEPTIBILITY OF NITRIC OXIDE AT 296 degrees K. AND 216 degrees K.

PMID- 16587508
TI  - HYPER-FINE STRUCTURE IN SPECTRAL LINES- ESPECIALLY THOSE OF SINGLY IONIZED
      PRASEODYMIUM.

PMID- 16587509
TI  - A METHOD OF PRODUCING LONG SINGLE-CRYSTALS OF METAL AND A STUDY OF THE FACTORS
      INFLUENCING CRYSTAL-ORIENTATION AND PERFECTION.

PMID- 16587510
TI  - HIGHER SPARK SPECTRA OF NEON AND ARGON IN THE EXTREME ULTRA-VIOLET.

PMID- 16587512
TI  - THE INVALIDITY OF A COMMON USED METHOD FOR COMPUTING A CERTAIN PROBABLE ERROR.

PMID- 16587511
TI  - RELATIVE PROBABILITIES OF THE IONIZATION OF K AND L ELECTRONS OF EQUAL IONIZATION
      ENERGY.

PMID- 16587513
TI  - ON CERTAIN FOURIER SERIES EXPANSIONS OF DOUBLY PERIODIC FUNCTIONS OF THE THIRD
      KIND.

PMID- 16587514
TI  - AUTOMORPHISM COMMUTATORS.

PMID- 16587515
TI  - ARITHMETIZED TRIGONOMETRICAL EXPANSIONS OF DOUBLY PERIODIC FUNCTIONS OF THE THIRD
      KIND.

PMID- 16587516
TI  - THE ENTROPY OF HYDROGEN.

PMID- 16587517
TI  - IRREVERSIBLE TRANSFORMATIONS OF ORGANIC COMPOUNDS UNDER HIGH PRESSURES:
      (Preliminary Paper).

PMID- 16587518
TI  - PROGRESS REPORT ON WEIGHT INCREASES IN LAMBS WITH AND WITHOUT RUMEN INFUSORIA.

PMID- 16587519
TI  - THE METHOD BY WHICH RUMINANTS ACQUIRE THEIR FAUNA OF INFUSORIA, AND REMARKS
      CONCERNING EXPERIMENTS ON THE HOST-SPECIFICITY OF THESE PROTOZOA.

PMID- 16587520
TI  - UNISEXUAL PROGENIES AND THE SEX CHROMOSOME MECHANISM IN SCIARA.

PMID- 16587521
TI  - FURTHER STUDIES ON THE CHROMOSOME MECHANISM RESPONSIBLE FOR UNISEXUAL PROGENIES
      IN SCIARA. TESTS OF EXCEPTIONAL MALES.

PMID- 16587522
TI  - CHANGES IN THE RATE OF MUTABILITY OF THE MUTABLE MINIATURE GENE OF DROSOPHILA
      VIRILIS.

PMID- 16587524
TI  - A PROPOSED PHYLOGENY OF THE ONAGRACEAE BASED PRIMARILY ON NUMBER OF CHROMOSOMES.

PMID- 16587523
TI  - CHROMOSOME NUMBER AND THE MUTATION RATE IN AVENA AND TRITICUM.

PMID- 16587525
TI  - THE CHROMOSOMES OF BUGINVILLAEA.

PMID- 16587526
TI  - NEW RESULTS FROM THE STUDY OF COELENTERATE NEMATOCYSTS: (Preliminary Note).

PMID- 16587527
TI  - AN INTERFEROMETER METHOD OF OBSERVING THE VIBRATIONS OF AN OSCILLATING QUARTZ
      PLATE.

PMID- 16587528
TI  - PERTURBATIONS IN BAND SPECTRA. II.

PMID- 16587529
TI  - ON GROUPS DEFINED BY A = 1, B AB = A, B = A.

PMID- 16587530
TI  - ON THE EXISTENCE OF INTEGRALS OF EINSTEIN'S GRAVITATIONAL EQUATIONS FOR FREE
      SPACE AND THEIR EXTENSION TO n VARIABLES.

PMID- 16587531
TI  - The First Two Cases of Crossing-Over between Old-Gold and Bullata Factors in the
      Third Linkage Group of Oenothera.

PMID- 16587532
TI  - Somatic Segregation Produced by X-Rays in Drosophila Melanogaster.

PMID- 16587534
TI  - Solid Protein Hydrochlorides.

PMID- 16587533
TI  - The Radial Velocities of Globular Clusters.

PMID- 16587535
TI  - The Structure of the Micas and Related Minerals.

PMID- 16587536
TI  - The Decomposition of Nitrogen Pentoxide at Low Pressures.

PMID- 16587537
TI  - Adsorption of Ammonia by Proteins.

PMID- 16587538
TI  - Determination of Some Properly Irregular Cyclotomic Fields.

PMID- 16587539
TI  - On an Extension of the Fourier Theorem Giving Rapid Methods for Calculating the
      Constant Part and the Coefficient of Any Periodic Term in the Disturbing
      Function.

PMID- 16587540
TI  - Content-Preserving Transformations.

PMID- 16587541
TI  - Simplicity with Respect to Certain Quadratic Forms.

PMID- 16587542
TI  - The Differential Geometry of a Continuous Infinitude of Contravariant functional
      Vectors.

PMID- 16587544
TI  - Non-Abelian Groups Admitting More Than Half Inverse Correspondencies.

PMID- 16587543
TI  - Projective Functional Tensors and Other Allied Functionals.

PMID- 16587545
TI  - Linear Transformations in Hilbert Space: III. Operational Methods and Group
      Theory.

PMID- 16587546
TI  - On the Diamagnetism of Electrons in Metals.

PMID- 16587547
TI  - On the Experimental Evidence of the Mosaic Structure of Bi-Single Crystals.

PMID- 16587548
TI  - Circle Formation in Datura and Oenothera.

PMID- 16587549
TI  - Interaction between Complexes as Evidence for Segmental Interchange in Oenothera.

PMID- 16587550
TI  - Pollen-Tube Growth of the Primary Mutant of Datura Rolled, and Its Two
      Secondaries.

PMID- 16587551
TI  - Operational Calculus in Quantum Mechanics. Some Critical Comments and the
      Solution of Special Problems.

PMID- 16587552
TI  - Physical Problems with Discontinuous Initial Conditions.

PMID- 16587553
TI  - On the Possible Influence of the Mosaic Structure of Crystals on the
      Determination of Avogadro's Number.

PMID- 16587555
TI  - The Implantation of Additional Hypophyseal Rudiments in Urodele Embryos.

PMID- 16587554
TI  - The Problem of Preparing Optically Active Free Radicals.

PMID- 16587556
TI  - The Cultivation of Treponemata from the Blood of Normal Monkeys (Macacus Rhesus)
      and from the Blood of Monkeys Infected with Yellow Fever.

PMID- 16587557
TI  - The Problems of Lagrange and Mayer Under General End Conditions.

PMID- 16587558
TI  - Concerning Perfect Continuous Curves.

PMID- 16587559
TI  - Combinatory Topology of Convex Regions.

PMID- 16587560
TI  - Some Remarks on the Problem of Plateau.

PMID- 16587561
TI  - The Problem of the Calculus of Variations in m-Space with End-Points Variable on
      Two Manifolds.

PMID- 16587562
TI  - On Some Statistical Properties of Double Stars in Space: I. A Formula for the
      Estimation of the Period in a Relatively Fixed System.

PMID- 16587563
TI  - On Some Statistical Properties of Double Stars in Space: II. On the Mean Period
      of Double Stars in Space.

PMID- 16587564
TI  - THE VELOCITIES OF B-TYPE STARS.

PMID- 16587565
TI  - GENETICAL AND CYTOLOGICAL STUDIES OF SEMISTERILITY AND RELATED PHENOMENA IN
      MAIZE.

PMID- 16587566
TI  - EVIDENCE THAT NATURAL RADIOACTIVITY IS INADEQUATE TO EXPLAIN THE FREQUENCY OF
      "NATURAL" MUTATIONS.

PMID- 16587567
TI  - THE INFLUENCE ON THE IDEAL SOLUTION LAWS OF THE DISTRIBUTION OF POLARITY WITHIN
      THE MOLECULE.

PMID- 16587568
TI  - PENTAVALENT NITROGEN IN ORGANIC COMPOUNDS.

PMID- 16587569
TI  - THE TAUTOMERIC FORM OF MALIC ACID.

PMID- 16587570
TI  - ON THE OVERCONVERGENCE OF SEQUENCES OF POLYNOMIALS OF BEST APPROXIMATION.

PMID- 16587571
TI  - SUMMARY OF RESULTS AND PROOFS ON FERMAT'S LAST THEOREM: (Fifth Paper).

PMID- 16587572
TI  - GROUPS GENERATED BY TWO GIVEN GROUPS.

PMID- 16587573
TI  - ON THE STRUCTURE OF PURE RIEMANN MATRICES WITH NON-COMMUTATIVE MULTIPLICATION
      ALGEBRAS.

PMID- 16587574
TI  - ON DIRECT PRODUCTS, CYCLIC DIVISION ALGEBRAS, AND PURE RIEMANN MATRICES.

PMID- 16587575
TI  - THE NEAR INFRA-RED ABSORPTION SPECTRUM OF CALCITE.

PMID- 16587576
TI  - THE EFFECT OF THE ANNIHILATION OF MATTER ON THE WAVE-LENGTH OF LIGHT FROM THE
      NEBULAE.

PMID- 16587578
TI  - ACTION CURRENTS IN THE AUDITORY NERVE IN RESPONSE TO ACOUSTICAL STIMULATION.

PMID- 16587577
TI  - ON THE DISTRIBUTION OF TABULAR ROOTS IN CEIBA (BOMBACACEAE).

PMID- 16587579
TI  - MUTATIONS AND ALLELOMORPHISM IN THE GROUSE LOCUSTS (TETTIGIDAE, ORTHOPTERA).

PMID- 16587580
TI  - THE ELECTROMAGNETIC FIELD EXTERIOR TO A SYSTEM OF PERFECTLY REFLECTING SURFACES.

PMID- 16587582
TI  - ON THE PREDICTIONS OF TRANS-NEPTUNIAN PLANETS FROM THE PERTURBATIONS OF URANUS.

PMID- 16587581
TI  - THE RATES OF SECOND-ORDER GAS REACTIONS.

PMID- 16587583
TI  - THE "REACTION-ISOCHORE" EQUATION FOR IONIZATION WITHIN METALS.

PMID- 16587584
TI  - THE EFFECT OF LOW TEMPERATURES ON THE SENSITIVITY OF RADIOMETERS.

PMID- 16587585
TI  - THE ORIGIN OF THE PLANTS OF MATERNAL TYPE WHICH OCCUR IN CONNECTION WITH
      INTERSPECIFIC HYBRIDIZATIONS.

PMID- 16587586
TI  - MELANOPHORE PULSATIONS IN THE ISOLATED SCALES OF FUNDULUS HETEROCLITUS.

PMID- 16587587
TI  - DIURNAL RHYTHM OF THE DISTAL PIGMENT CELLS IN THE EYES OF CERTAIN CRUSTACEANS.

PMID- 16587588
TI  - THE COLOR CHANGES OF THE TREE TOAD IN RELATION TO NERVOUS AND HUMORAL CONTROL.

PMID- 16587589
TI  - GROUP OF ISOMORPHISMS OF AN ABELIAN GROUP.

PMID- 16587591
TI  - AN EXTENSION OF THE ALEXANDER DUALITY THEOREM.

PMID- 16587592
TI  - MORE COMPLETE DISCUSSION OF THE TIME-DEPENDENCE OF THE NON-STATIC LINE ELEMENT
      FOR THE UNIVERSE.

PMID- 16587590
TI  - COALESCENCE OF PARTS OF A COMPLEX.

PMID- 16587593
TI  - THE SIGNIFICANCE OF RECENT COSMIC-RAY EXPERIMENTS.

PMID- 16587594
TI  - MOTION ON A LATTICE.

PMID- 16587595
TI  - THE ABSORPTION COEFFICIENT OF HARD gamma-RAYS.

PMID- 16587596
TI  - ON THE CONDITIONS OF ELICITATION OF CERTAIN EATING REFLEXES.

PMID- 16587597
TI  - THE ENERGY REQUIREMENTS OF INTENSE MENTAL EFFORT.

PMID- 16587598
TI  - BENDING OF CURVED TUBES.

PMID- 16587599
TI  - GROUPS WHICH ARE DECOMPOSABLE INTO TWO NON-INVARIANT CYCLIC SUBGROUPS.

PMID- 16587600
TI  - ON THE DUALITY THEOREMS FOR THE BETTI NUMBERS OF TOPOLOGICAL MANIFOLDS.

PMID- 16587601
TI  - RECIPROCAL TRANSLOCATIONS IN DROSOPHILA AND THEIR BEARING ON OENOTHERA CYTOLOGY
      AND GENETICS.

PMID- 16587603
TI  - THE NATURE OF THE PROSTHETIC GROUP IN LIMULUS HEMOCYANIN.

PMID- 16587602
TI  - NOTES ON THE PLASTID AND OTHER CYTOPLASMIC BODIES DURING SPOROGENESIS AND
      SPERMATOGENESIS IN POLYTRICHUM COMMUNE.

PMID- 16587604
TI  - THE PHOTOCHEMICAL DISSOCIATION OF NITROGEN PEROXIDE.

PMID- 16587605
TI  - THE STUDY OF ABSORPTION SPECTRA OF ORGANIC COMPOUNDS AT LIQUID AIR TEMPERATURES.

PMID- 16587606
TI  - THE ROLE OF CHEMICAL STIMULATION IN THE SPAWNING REACTIONS OF OSTREA VIRGINICA
      AND OSTREA GIGAS.

PMID- 16587607
TI  - ON THE FREE ENERGY OF GLUCOSE AND OF TRIPALMITIN.

PMID- 16587608
TI  - CLAUDE BERNARD'S THEORY OF NARCOSIS.

PMID- 16587609
TI  - THE STRUCTURE OF THE CHLORITES.

PMID- 16587611
TI  - ON THE SUMMABILITY OF FOURIER SERIES. THIRD NOTE.

PMID- 16587610
TI  - DISCUSSION OF VARIOUS TREATMENTS WHICH HAVE BEEN GIVEN TO THE NON-STATIC LINE
      ELEMENT FOR THE UNIVERSE.

PMID- 16587612
TI  - THE ARCHITECTURE OF LIVING CELLS-RECENT ADVANCES IN METHODS OF BIOLOGICAL
      RESEARCH-OPTICAL SECTIONING WITH THE ULTRA-VIOLET MICROSCOPE.

PMID- 16587613
TI  - A FUNDAMENTAL THEOREM ON ONE-PARAMETER CONTINUOUS GROUPS OF PROJECTIVE FUNCTIONAL
      TRANSFORMATIONS.

PMID- 16587614
TI  - A SPECIAL TYPE OF UPPER SEMI-CONTINUOUS COLLECTION.

PMID- 16587615
TI  - ON EXPANSIONS OF ARITHMETICAL FUNCTIONS.

PMID- 16587616
TI  - QUADRATIC FUNCTIONAL FORMS IN A COMPOSITE RANGE.

PMID- 16587617
TI  - THE MIXED PROBLEM FOR LAPLACE'S EQUATION IN THE PLANE DISCONTINUOUS BOUNDARY
      VALUES.

PMID- 16587618
TI  - The Independence of Dominant Spotting and Recessive Spotting ("Piebald") in the
      House Mouse.

PMID- 16587619
TI  - The Interpretation of the Thermal Decomposition of Nitrous Oxide.

PMID- 16587620
TI  - Reversible Coagulation in Living Tissue: I.

PMID- 16587621
TI  - On the Unified Field Theory: IV.

PMID- 16587622
TI  - The Arithmetic of Polynomials in a Galois Field.

PMID- 16587623
TI  - The Coloring of Graphs.

PMID- 16587624
TI  - Non-Separable and Planar Graphs.

PMID- 16587625
TI  - The Principle of Maupertuis.

PMID- 16587626
TI  - Notes on Scalar Extensions of Tensors and Properties of Local Coordinates.

PMID- 16587628
TI  - The California Earthquakes of Nov. 28, 1929, and the Surface Layers of the Earth
      in California.

PMID- 16587627
TI  - On the Specific Dynamic Action of Protein.

PMID- 16587629
TI  - Immunity to Sugar Cane Mosaic Acquired by the Host.

PMID- 16587630
TI  - Cytological Evidence for Segmental Interchange between Non-Homologous Chromosomes
      in Maize.

PMID- 16587631
TI  - The Behavior of the Virus of Yellow Fever in Monkeys and Mice.

PMID- 16587632
TI  - The Heat of Combustion of Methyl Alcohol.

PMID- 16587633
TI  - A Potentiometric Study of Epinephrine.

PMID- 16587634
TI  - The Distribution of Stresses in Welded and Riveted Connections.

PMID- 16587635
TI  - The Relative Effectiveness of Spectral Radiation for the Vision of the Sun-Fish,
      Lepomis.

PMID- 16587636
TI  - Systems of Algebraic Differential Equations.

PMID- 16587637
TI  - The Number of Representations Function for Positive Binary Quadratic Forms.

PMID- 16587638
TI  - Dynamical Trajectories and the infinity Plane Sections of a Surface.

PMID- 16587639
TI  - On the Summability of Fourier Series. Fourth Note.

PMID- 16587641
TI  - Normal Division Algebras of 2.

PMID- 16587640
TI  - On the Stability of the Motion of a Viscous Fluid.

PMID- 16587642
TI  - Electric Conductivity and Optical Absorption in Metals, Once More.

PMID- 16587643
TI  - The Spectral Erythemic Reaction of the Human Skin to Ultra-Violet Radiation.

PMID- 16587644
TI  - The Physical Basis of Modern Hydrographic Surveying.

PMID- 16587645
TI  - A Metric for the Space of Measurable Functions.

PMID- 16587646
TI  - The Euler Equations of Problems of the Calculus of Variations with Prescribed
      Transversality Conditions.

PMID- 16587647
TI  - Theorems Relating to the History of Mathematics.

PMID- 16587648
TI  - On the Intensity of Total Scattering of X-Rays by Gases: I.

PMID- 16587649
TI  - On the Intensity of Total Scattering of X-Rays by Gases: II.

PMID- 16587650
TI  - Note on Scattering by Diatomic Gases.

PMID- 16587651
TI  - The Solid Solution Theory of Dyeing.

PMID- 16587652
TI  - Reversible Coagulation in Living Tissue: V.

PMID- 16587653
TI  - The Order of the Genes C, Sh and Wx in Zea Mays with Reference to a Cytologically
      Known Point in the Chromosome.

PMID- 16587655
TI  - A Reverse Mutation from "Dilute" to "Intense" Pigmentation in the House Mouse.

PMID- 16587654
TI  - A Correlation of Cytological and Genetical Crossing-Over in Zea Mays.

PMID- 16587656
TI  - Matthiola Incana: Trisomic Inheritance of Doubleness, Complicated by Lethals, in.

PMID- 16587657
TI  - The Chromosomes of Lathyrus Tuberosus.

PMID- 16587658
TI  - Evidence for Multiple Sex Factors in the X-Chromosome of Drosophila Melanogaster.

PMID- 16587659
TI  - Body Pattern as Related to Mammary Gland Secretion.

PMID- 16587660
TI  - Why Crystals Exist.

PMID- 16587661
TI  - On the Air Resistance of Projectiles.

PMID- 16587662
TI  - High Vacuum Pressure Control Apparatus.

PMID- 16587663
TI  - On the Relation between the Expansion and the Mean Density of the Universe.

PMID- 16587664
TI  - Azo Derivatives of the Pyrimidines.

PMID- 16587665
TI  - Some Effects of High Temperature on Polyploidy and Other Variations in Maize.

PMID- 16587666
TI  - Note on the Quantum Dynamical Correction of the Equation of State.

PMID- 16587667
TI  - Effect of Nuclear Spin on the Radiation Excited by Electron Impact.

PMID- 16587668
TI  - Entropy, Reversible Processes and Thermo-Couples.

PMID- 16587670
TI  - On the Field of Values of a Square Matrix.

PMID- 16587669
TI  - Comments on the Note by E. H. Kennard on "Entropy, Reversible Processes and
      Thermo-Couples".

PMID- 16587671
TI  - Remarks on the Ergodic Theory of Birkhoff.

PMID- 16587672
TI  - A Geometrical Determination of the Canonical Quadric of Wilczynski.

PMID- 16587674
TI  - Physical Applications of the Ergodic Hypothesis.

PMID- 16587673
TI  - Dynamical Systems of Continuous Spectra.

PMID- 16587675
TI  - Complex Geometry and Relativity; Theory of the "Rac" Curvature.

PMID- 16587676
TI  - Regular Families of Curves: I.

PMID- 16587677
TI  - Recent Contributions to the Ergodic Theory.

PMID- 16587679
TI  - The Miocene Flora of Idaho.

PMID- 16587678
TI  - On the Numerations of the Continued Fraction.

PMID- 16587680
TI  - Interatomic Distances in Covalent Molecules and Resonance between Two or More
      Lewis Electronic Structures.

PMID- 16587681
TI  - The Penetration of 1-Naphthol-2-Sulphonate Indophenol, o-Chloro Phenol Indophenol
      and o-Cresol Indophenol into Species of Valonia from the South Seas.

PMID- 16587682
TI  - Studies on Mouse Leukemia: VI. The Predominating Cell Type in Line I.

PMID- 16587683
TI  - A Critique of Recent Quantum Theories: II.

PMID- 16587684
TI  - The Ionization of Argon and Neon by Neutral Argon Beams.

PMID- 16587685
TI  - Ionization in Gases by Ions and Atoms.

PMID- 16587687
TI  - An Instrument for the Photometering of the New X-Ray Lines.

PMID- 16587686
TI  - The Mass of the Electron.

PMID- 16587688
TI  - The Pressure Variation of the Heat Function as a Direct Measure of the van der
      Waals Forces.

PMID- 16587689
TI  - Proof of Gibbs' Hypothesis on the Tendency toward Statistical Equilibrium.

PMID- 16587690
TI  - Regular Families of Curves: II.

PMID- 16587691
TI  - Interaction of Ruffled and Rounded Genes of Drosophila Virilis.

PMID- 16587692
TI  - The Maturation Divisions and Fertilization in Eggs of Sciara Coprophila: Lint.

PMID- 16587693
TI  - Elimination of Chromosomes during Cleavage in the Eggs of Sciara (Diptera).

PMID- 16587694
TI  - Xenia and Metaxenia in Apples: II.

PMID- 16587695
TI  - Notes on Stellar Statistics: V. On the Use of the First Laplacean Error Curve.

PMID- 16587696
TI  - The Application of Photoelectric Cells Sensitive in the Infra-Red to Stellar
      Photometry.

PMID- 16587698
TI  - The Ciliation of the Oviducts of Reptiles.

PMID- 16587697
TI  - The Rotational Structure of the Ultra-Violet Absorption Bands of Formaldehyde.

PMID- 16587699
TI  - The Combination of Carbon Monoxide and Oxygen under the Influence of Radon.

PMID- 16587700
TI  - "Feather Joints" as Indicators of the Direction of Movements on Faults, Thrusts,
      Joints and Magmatic Contacts.

PMID- 16587702
TI  - Sphere Geometry and the Conformal Group in Function Space.

PMID- 16587701
TI  - On Certain Criteria for Fourier Constants of L Integrable Functions.

PMID- 16587703
TI  - Concerning Uniordered Spaces.

PMID- 16587704
TI  - Remarks on a Theorem of D. V. Widder.

PMID- 16587705
TI  - On the Scattering of Light by Supersonic Waves.

PMID- 16587706
TI  - The Additivity of the Energies of Normal Covalent Bonds.

PMID- 16587707
TI  - Investigations in the Retene Field: II. alpha-Retene Carboxylic Acid and Some of
      Its Derivatives.

PMID- 16587708
TI  - Changes in the Cells of Spirogyra Associated with the Presence of Water Polymers.

PMID- 16587709
TI  - Character Recombination in Drosophila.

PMID- 16587710
TI  - Effect of Temperature on the Rate of Change of the Unstable Miniature-3 Gamma
      Gene of Drosophila Virilis.

PMID- 16587711
TI  - An Interchange in Maize Giving Low Sterility and Chain Configurations.

PMID- 16587712
TI  - A Strain of Maize Homozygous for Segmental Interchanges Involving Both Ends of
      the P-br Chromosome.

PMID- 16587713
TI  - Chromosome Rings in Maize and Oenothera.

PMID- 16587714
TI  - On the Stability of Physiological Characters of Bacteria.

PMID- 16587715
TI  - Concerning Sequences of Homeomorphisms.

PMID- 16587716
TI  - An Improved Equal-Frequency Map of the Normal Correlation Surface, Using Circles
      Instead of Ellipses.

PMID- 16587717
TI  - Modular Homology Characters.

PMID- 16587718
TI  - Orders for Which a Given Number of Groups Exist.

PMID- 16587719
TI  - Geometry of the Heat Equation: First Paper.

PMID- 16587720
TI  - Minnesota Pleistocene Homo-An Interim Communication.

PMID- 16587721
TI  - The Behavior of Interchange Heterozygotes in Oenothera.

PMID- 16587722
TI  - Prime Types in Datura.

PMID- 16587723
TI  - Methods of Synthesizing Pure-Breeding Types with Predicted Characters in the
      Jimson Weed, Datura Stramonium.

PMID- 16587724
TI  - Eversporting as a Function of the Y-Chromosome in Drosophila Melanogaster.

PMID- 16587725
TI  - The Higher Crystalline Plateau of Southeastern Brazil.

PMID- 16587726
TI  - Structure of the "Ellicott City Granite," Maryland.

PMID- 16587727
TI  - Xenohelix in the Maryland Miocene.

PMID- 16587728
TI  - Conference of the Symbols, Units and Nomenclature (S. U. N.) Commission of the
      International Union of Pure and Applied Physics (I. P. U.) at Paris, in July,
      1932, and Its Results.

PMID- 16587729
TI  - Higher Processes in the Behavior of Rats.

PMID- 16587730
TI  - A Phylogenetic Consideration of the Optic Tectum.

PMID- 16587731
TI  - The in Vitro Respiration of Nerve.

PMID- 16587732
TI  - Observations on the Nervous Control of Respiratory Movements.

PMID- 16587733
TI  - On the Metabolism of the Pancreas.

PMID- 16587734
TI  - Paleozoic Planktonic Faunas of North America.

PMID- 16587735
TI  - Biological Inductions from the Evolution of the Proboscidea.

PMID- 16587736
TI  - The Time of Embryonic Segregation in Aphids as Determined from Intermediate
      Types.

PMID- 16587737
TI  - The Cellular Transmission of Neurohumoral Substances in Melanophore Reactions.

PMID- 16587738
TI  - Preliminary Account of Deep Sea Dives in the Bathysphere with Especial Reference
      to One of 2200 Feet.

PMID- 16587739
TI  - A Step-Polygon of a Denumerable Infinity of Sides Which Bounds No Finite Area.

PMID- 16587740
TI  - Crescent-Shaped Minimal Surfaces.

PMID- 16587742
TI  - Interpolation and an Analogue of the Laurent Development.

PMID- 16587741
TI  - Groups Generated by Two Operators of Order 3 Whose Commutator Is of Order 2.

PMID- 16587743
TI  - Experiments upon the Segmentation of Spinal Nerves in Salamander Embryos.

PMID- 16587744
TI  - A Contribution to the Study of Galactic Dimensions.

PMID- 16587746
TI  - A Simple Derivation of the Dissociation Formula.

PMID- 16587745
TI  - The Theoretical Frequency Distribution of Photographic Meteors.

PMID- 16587747
TI  - A Suggested Mechanism of Class Be Stars.

PMID- 16587748
TI  - Host Specialization of Erysiphe graminis Tritici.

PMID- 16587749
TI  - Regeneration in Mutilated Seedlings.

PMID- 16587750
TI  - The Use of Non-Aqueous Solvents in the Study of the Rare Earth Group.

PMID- 16587751
TI  - The Determination of the Structures of the Hexafluorides of Sulfur, Selenium and
      Tellurium by the Electron Diffraction Method.

PMID- 16587752
TI  - The Functions of the Olfactory Parts of the Cerebral Cortex.

PMID- 16587753
TI  - The Agglomeration Theory of Sleep.

PMID- 16587754
TI  - The Zero Point Energy and the Separation of Isotopes.

PMID- 16587755
TI  - The Reaction of Hydrogen Atoms with Oxygen and the Hydrogen Chlorine Reaction.

PMID- 16587756
TI  - Reversible Coagulation in Living Tissue: XI.

PMID- 16587757
TI  - Blood Group Inheritance in the Rabbit.

PMID- 16587759
TI  - The Newton-Denning Method for Computing Meteor Paths with a Celestial Globe.

PMID- 16587758
TI  - Tests for Linkage between the Blood-Group Genes and Other Known Genes of the
      Rabbit.

PMID- 16587760
TI  - A Study of Meteor Light Curves.

PMID- 16587761
TI  - Absorption and Space Reddening in the Galaxy as Shown by the Colors of Globular
      Clusters.

PMID- 16587762
TI  - Available Food, Relative Growth and Duration of Life in Seedlings of Cucumis
      Melo.

PMID- 16587763
TI  - An X-Ray Induced Chromosomal Translocation in Apotettix eurycephalus Hancock
      (Grouse Locusts).

PMID- 16587765
TI  - Characters of Abelian Groups.

PMID- 16587766
TI  - Geometry of the Heat Equation: Second Paper. The Three Degenerate Types of
      Laplace, Poisson and Helmholtz.

PMID- 16587764
TI  - The Geology of the Beartooth Mountain Front in Park County, Wyoming.

PMID- 16587767
TI  - Theory of Elastic Systems Vibrating under Transient Impulse with an Application
      to Earthquake-Proof Buildings.

PMID- 16587769
TI  - On Lacunary Power Series.

PMID- 16587768
TI  - A Jordan Space Curve Which Bounds No Finite Simply Connected Area.

PMID- 16587770
TI  - A Matrix Knot Invariant.

PMID- 16587771
TI  - Akhissar Spotting of the House Mouse.

PMID- 16587772
TI  - A Miacid from the Sespe Upper Eocene, California.

PMID- 16587773
TI  - Effect of Methylthionine Chloride on Phytotoxic Reaction of Normal and
      Pathological Blood.

PMID- 16587775
TI  - Notes on Blood-Groups and Race in the Pacific.

PMID- 16587774
TI  - A Physical Analysis of Wolf-Rayet Spectra.

PMID- 16587776
TI  - The Excitation Potential of the lambda 2883 and lambda 2895 Bands of Carbon
      Dioxide.

PMID- 16587777
TI  - Geometry of Four-Component Spinors.

PMID- 16587778
TI  - Contribution to the Theory of Scattering by a Force Center.

PMID- 16587779
TI  - The Influence of Intensity, Color and Retinal Location on the Fusion Frequency of
      Intermittent Illumination.

PMID- 16587780
TI  - Color Changes in Fundulus with Special Reference to the Color Changes of the
      Iridosomes.

PMID- 16587781
TI  - The Cauchy-Goursat Theorem for Rectifiable Jordan Curves.

PMID- 16587782
TI  - An Inequality for Legendre Series Coefficients.

PMID- 16587783
TI  - The Geometry of Degenerate Heat Families.

PMID- 16587784
TI  - On Statistical Methods in the Theory of Almost-Periodic Functions.

PMID- 16587785
TI  - Sylow Subgroups and the Number of Operators Whose Orders Are Powers of the Same
      Prime.

PMID- 16587786
TI  - Values of T(mu) and Christoffel Symbols for a Line Element of Considerable
      Generality.

PMID- 16587787
TI  - On Non-Factorable Transformations of Double Sequences.

PMID- 16587788
TI  - The Method of Spectral Reduction in Classical Dynamics.

PMID- 16587789
TI  - Questions of Relative Inclusion in the Domain of Hausdorff Means.

PMID- 16587790
TI  - Finite Ova.

PMID- 16587791
TI  - Forbidden Lines in Astrophysical Sources.

PMID- 16587792
TI  - Luminosity Distribution and Average Density of Matter in Twenty-Five Groups of
      Galaxies.

PMID- 16587793
TI  - Absorption and Space Reddening in the Galaxy from the Colors of B-Stars.

PMID- 16587794
TI  - Preliminary Studies of Chromosome Rings in Brodiaea Lactea.

PMID- 16587795
TI  - Absence of the Corpus Callosum as a Mendelizing Character in the House Mouse.

PMID- 16587796
TI  - The Topology of Involutions.

PMID- 16587797
TI  - On Supraconductivity and the Hall Effect.

PMID- 16587798
TI  - The Katabolism of the Non-Volatile Organic Acids of Tobacco Leaves during Curing.

PMID- 16587799
TI  - The Energy of Urea Synthesis.

PMID- 16587800
TI  - On the Inheritance of Diabetes Mellitus.

PMID- 16587801
TI  - Growth-Promoting Substance and Illumination.

PMID- 16587802
TI  - The Effect of Ice and Steam Water on Euglena.

PMID- 16587804
TI  - Transformations Preserving the Tetrad Equations.

PMID- 16587803
TI  - Neon Absorption Lines in Stellar Spectra.

PMID- 16587805
TI  - Color Changes in the Isolated Scale Iridocytes of the Squirrel Fish, Holocentrus
      Ascensionis (Osbeck).

PMID- 16587806
TI  - Multiple Tests in the Foraminifera.

PMID- 16587807
TI  - An Extremal Problem in Analytic Functions.

PMID- 16587809
TI  - On the Theory of Laplace Integrals.

PMID- 16587808
TI  - On Moment Functions.

PMID- 16587810
TI  - A Lower Limit for the Species of a Pfaffian System.

PMID- 16587811
TI  - A Property of Recurring Series.

PMID- 16587812
TI  - Intensities in Atomic Spectra.

PMID- 16587813
TI  - The Biogeographic Relations of the Orbitoid Foraminifera.

PMID- 16587814
TI  - On the Linear Diameters of 125 Large Galaxies.

PMID- 16587815
TI  - Linkage Interrelations of Three Genes for Rex (Short) Coat in the Rabbit.

PMID- 16587816
TI  - The Gene Theory in Relation to Blending Inheritance.

PMID- 16587818
TI  - The Specific Formula of Heredity.

PMID- 16587817
TI  - The Effect of X-Ray Dosage on Sterility and Number of Lethals in Drosophila
      melanogaster.

PMID- 16587819
TI  - A Cytogenetical Study of a Reciprocal Translocation in Zea.

PMID- 16587820
TI  - A Secondary Trisome in Maize.

PMID- 16587821
TI  - The Color Changes of Elasmobranch Fishes.

PMID- 16587822
TI  - On Overlap.

PMID- 16587823
TI  - On the Temperature Dependence of Ferro-Magnetic Saturation.

PMID- 16587824
TI  - A Duality in Interpolation to Analytic Functions by Rational Functions.

PMID- 16587825
TI  - Groups Involving a Small Number of Squares.

PMID- 16587826
TI  - A Theory for -Operators Analogous to the Theory of Reducibility for Self-Adjoint
      Transformations in Hilbert Space.

PMID- 16587827
TI  - Separation of Hydrogen Isotopes by Diffusion through Palladium.

PMID- 16587828
TI  - Summary of a Variable Star Survey in an External Galaxy.

PMID- 16587830
TI  - Polyisomerism and Anisomerism in Cranial and Dental Evolution among Vertebrates.

PMID- 16587829
TI  - The Terrestrial Abundance of the Permanent Gases.

PMID- 16587831
TI  - Evolution of the Expanding Universe.

PMID- 16587832
TI  - An Investigation of the Stresses in Longitudinal Welds.

PMID- 16587833
TI  - On the Dynamical Theory of Electrical Commutator Machines.

PMID- 16587834
TI  - The Nature of the Depressor Substance of the Blood.

PMID- 16587835
TI  - Effect of X-Rays on the Rate of Change in the Unstable Miniature-3 Gene of the
      Drosophila virilis.

PMID- 16587837
TI  - On the Occurrence of Translocations and Autosomal Non-Disjunction in Drosophila
      melanogaster.

PMID- 16587836
TI  - Evidence Indicating that in Sciara the Sperm Regularly Transmits Two Sister Sex
      Chromosomes.

PMID- 16587838
TI  - Unisexual Maize Plants and Their Relation to Dioecism in Other Organisms.

PMID- 16587839
TI  - Concerning Compact Continua Which Contain No Continuum That Separates the Plane.

PMID- 16587840
TI  - Does Instability Imply Transitivity?

PMID- 16587841
TI  - On Distribution Functions and Their Laplace-Fourier Transforms.

PMID- 16587842
TI  - On the Asymptotic Formulae of Riemann and of Laplace.

PMID- 16587843
TI  - Functions Orthogonal in the Hermitian Sense. A New Application of Basic Numbers.

PMID- 16587844
TI  - The Expansion of the Universe and the Intensity of Cosmic Rays.

PMID- 16587845
TI  - Scientific Work in the "Century of Progress" Stratosphere Balloon.

PMID- 16587846
TI  - Analysis of Non-Commuting Vectors with Application to Quantum Mechanics and
      Vector Calculus.

PMID- 16587847
TI  - Projective Differentiation in Spinors.

PMID- 16587848
TI  - Active and Passive Immunization in Typhus Fever.

PMID- 16587849
TI  - Possible Cytoplasmic as Well as Chromosomal Control of Sex in Haploid Males.

PMID- 16587850
TI  - Mutation Rate Increased by Aging Seeds as Shown by Pollen Abortion.

PMID- 16587852
TI  - Notes on Intensities in the Spectrum O II.

PMID- 16587851
TI  - Three Cases of Deficiency in Chromosome 9 of Zea mays.

PMID- 16587853
TI  - On the Vector Model for Almost Closed Shells.

PMID- 16587854
TI  - Can Mammalian Eggs Undergo Normal Development in Vitro?

PMID- 16587855
TI  - Achromobacter Ichthyodermis, N. Sp., The Etiological Agent of an Infectious
      Dermatitis of Certain Marine Fishes.

PMID- 16587857
TI  - General Theorems on Trajectories and Lines of Force.

PMID- 16587856
TI  - Minimum Number of Squares in a Group When Not All of Them Are Relatively
      Commutative.

PMID- 16587858
TI  - On the Metrical Transitivity of the Geodesics on a Surface of Constant Negative
      Curvature.

PMID- 16587859
TI  - On the Theory of Laplace Integrals: II.

PMID- 16587860
TI  - The Diameter of the Andromeda Nebula.

PMID- 16587862
TI  - Survival of Young Rabbit Embryos on Artificial Media.

PMID- 16587861
TI  - Haploids in Hordeum Vulgare.

PMID- 16587863
TI  - A Diploid Female Gametophyte of Sphaerocarpos.

PMID- 16587864
TI  - A Second Eocene Primate from California.

PMID- 16587865
TI  - Coincidence and Interference in Drosophila melanogaster.

PMID- 16587866
TI  - The Role of the "Chromosome Sheath" in Mitosis, and Its Possible Relation to
      Phenomena of Mutation.

PMID- 16587867
TI  - Development of the Embryo Sac of Lilium Henryi.

PMID- 16587868
TI  - The Ultra-Violet Absorption Spectrum of Carbon Suboxide Gas.

PMID- 16587869
TI  - Effect of Inhomogeneity on Cosmological Models.

PMID- 16587870
TI  - Elastic Wave Analogies to the Motion of Electrons in Force Fields.

PMID- 16587871
TI  - A Theory of Protein Metabolism in Man.

PMID- 16587872
TI  - On the Motion of Growth: VIII. The Connection between Growth and Heat Production
      in the Amphibian, Bufo vulgaris, from Fertilization to Metamorphosis.

PMID- 16587873
TI  - The Resolution of Four Tests.

PMID- 16587874
TI  - On Resolution into Generals and Specifics.

PMID- 16587875
TI  - Boolean Algebras and Their Application to Topology.

PMID- 16587876
TI  - Groups Whose Squares Constitute Cyclic Subgroups.

PMID- 16587877
TI  - Average Distribution of Arbitrary Masses under Group Translations.

PMID- 16587878
TI  - Entire Functions and Borel's Directions.

PMID- 16587879
TI  - The Reduction of Degenerate Quadratic Differential Forms.

PMID- 16587880
TI  - Causes of Color Change in Blue-Green Algae.

PMID- 16587882
TI  - Cosmic Rays from Super-Novae.

PMID- 16587883
TI  - The Velocity-Distance Relation for Isolated Extragalactic Nebulae.

PMID- 16587881
TI  - On Super-Novae.

PMID- 16587884
TI  - Heat Induced Mutations in Drosophila.

PMID- 16587885
TI  - Blood-Group Incompatibility in Rabbit Embryos and in Man.

PMID- 16587886
TI  - Linkage Studies of Brachyury (Short Tail) in the House Mouse.

PMID- 16587887
TI  - Miocene Patagonia.

PMID- 16587888
TI  - On Certain Invariants of Closed Extremals.

PMID- 16587889
TI  - Confusions in the Use of the Mathematical Term Group.

PMID- 16587890
TI  - The Strontium II and Barium II Spectra.

PMID- 16587891
TI  - The Effect of Intensity and Wave-Length on the Response of Avena to Light.

PMID- 16587892
TI  - Temperature Coefficient of Nerve Degeneration.

PMID- 16587893
TI  - The Prolonged Activity of Momentarily Stimulated Nerves.

PMID- 16587894
TI  - The Central Nervous Mechanism for Emotional Responses: II. A Technique for
      Destroying the Deeper Nuclear Regions within the Cerebrum with a Minimal
      Destruction of the Intervening Cortex.

PMID- 16587895
TI  - Raiding and Other Outstanding Phenomena in the Behavior of Army Ants.

PMID- 16587897
TI  - Ammonium and Potassium Molybdo-Tellurates, Two Homeomorphous Orthorhombic
      Substances.

PMID- 16587896
TI  - The Energies of the Atomic Linkages in the Normal Paraffin Hydrocarbons.

PMID- 16587899
TI  - The Structure of the Carboxyl Group: II. The Crystal Structure of Basic Beryllium
      Acetate.

PMID- 16587898
TI  - The Structure of the Carboxyl Group: I. The Investigation of Formic Acid by the
      Diffraction of Electrons.

PMID- 16587900
TI  - Neglected Factors in the Development of Thermal Springs.

PMID- 16587901
TI  - Microsyopsinae and Hyopsodontidae in the Sespe Upper Eocene, California.

PMID- 16587902
TI  - Biological Action of Small Deficiencies of X-Chromosome of Drosophila
      melanogaster.

PMID- 16587903
TI  - Ontogeny and Phylogeny of Man's Appendages.

PMID- 16587904
TI  - The Reaction of the Stigmatic Tissue against Pollen-Tube Growth in Selfed Self
      Sterile Plants.

PMID- 16587906
TI  - Groups of Order 2 Whose Squared Elements Constitute a Cyclic Subgroup.

PMID- 16587905
TI  - On the Summability of Fourier Series. Fifth Note.

PMID- 16587907
TI  - Stochastic Processes and Statistics.

PMID- 16587908
TI  - Remarks on the Possible Failure of Energy Conservation.

PMID- 16587909
TI  - The Dirac Equation in Projective Relativity.

PMID- 16587910
TI  - The Potentialities of Extreme Old Age.

PMID- 16587911
TI  - Studies on the Growth Hormone of Plants: V. The Relation of Cell Elongation to
      Cell Wall Formation.

PMID- 16587912
TI  - A Test of the Possible Effect of Visual Stimuli upon the Hair Color of Mammals.

PMID- 16587913
TI  - The Accuracy of Least Squares Solutions: Part II: The Standard Deviation of the
      Errors of Linear Equations of Condition.

PMID- 16587914
TI  - CHROMOSOME NUMBERS IN CERTAIN RICCIACEAE.

PMID- 16587916
TI  - Genetics of Hermaphroditism in Drosophila virilis.

PMID- 16587915
TI  - Reversible Coagulation in Living Tissue: XIII.

PMID- 16587917
TI  - Internal Organization of Salivary Gland Chromosomes of Sciara in Relation to
      Genes.

PMID- 16587918
TI  - Body Size of Reciprocal Hybrids in Rabbit Crosses.

PMID- 16587919
TI  - A Hypertragulid from the Sespe Uppermost Eocene, California.

PMID- 16587921
TI  - On the Expansion or Contraction of a Symmetrical Cloud under the Influence of
      Gravity.

PMID- 16587920
TI  - Ultra-Violet Transmission Changes in Glass as a Function of the Wave-Length of
      the Radiation Stimulus.

PMID- 16587922
TI  - To What Extent Is Developmental Block Dependent upon the Metabolic Activity of
      the Embryonic Cell?

PMID- 16587923
TI  - A Theoretical Basis for Intensity Discrimination in Vision.

PMID- 16587924
TI  - The Development of Rat Embryos in Tissue Culture.

PMID- 16587925
TI  - Eye-Stalk Hormone and the Movement of Distal Retinal Pigment in Palaemonetes.

PMID- 16587926
TI  - The Dissection of Closed Surfaces and the Phragmen-Brouwer-Alexandroff Theorem.

PMID- 16587927
TI  - The Intersection of Arbitrary Chains and Its Boundary.

PMID- 16587928
TI  - The General Case of Linear Integro-Differential Equations.

PMID- 16587929
TI  - Conformal Tensor Invariants.

PMID- 16587930
TI  - Involutorial Simple Algebras and Real Riemann Matrices.

PMID- 16587931
TI  - Subsumption of the Theory of Boolean Algebras under the Theory of Rings.

PMID- 16587933
TI  - Electrical Resistances and Volume Changes up to 20,000 Kg./Cm.

PMID- 16587932
TI  - Locally Compact Rings.

PMID- 16587934
TI  - Separation of Rotational Coordinates from the Schrodinger Equation for N
      Particles.

PMID- 16587935
TI  - Plesiomiacis, a New Creodont from the Sespe Upper Eocene, California.

PMID- 16587936
TI  - Protoplasmic Potentials in Halicystis: V. The Reversal of Potential by Unbalanced
      NaCl.

PMID- 16587937
TI  - How Do Electrolytes Enter the Cell?

PMID- 16587938
TI  - Degeneration of Xanthophores in Fundulus Majalis.

PMID- 16587939
TI  - Regeneration of Chromatophore Nerves.

PMID- 16587940
TI  - Inert Regions of Chromosomes as the Temporary Products of Individual Genes.

PMID- 16587941
TI  - Observations on the Structure of Living Salivary Gland Chromosomes in Sciara.

PMID- 16587942
TI  - Genetics of Sensory Thresholds: Variations within Single Individuals in Taste
      Sensitivity for PTC.

PMID- 16587943
TI  - Genetics of Sensory Thresholds: Individual Taste Reactions for Different
      Substances.

PMID- 16587945
TI  - Generalized Minimax Principle in the Calculus of Variations.

PMID- 16587944
TI  - Somatic Segregation Due to Hemizygous and Missing Genes and Its Bearing on the
      Problem of Atypical Growth.

PMID- 16587947
TI  - Preliminary Note Concerning a New Theory of the Motions of the Stars.

PMID- 16587946
TI  - Natural Isoperimetric Conditions in the Calculus of Variations.

PMID- 16587948
TI  - The Correlation of Cytological and Genetical Crossing-Over in Zea Mays. A
      Corroboration.

PMID- 16587949
TI  - Two Hereditary Types of Hydrocephalus in the House Mouse (Mus musculus).

PMID- 16587950
TI  - Studies on the "Diffusion Effect" upon Ionic Distribution. Some Theoretical
      Considerations.

PMID- 16587951
TI  - On the Foundation of a Constructive Theory of Discrete Commutative Algebra
      (Second Paper).

PMID- 16587952
TI  - Conformal-Affine Connections.

PMID- 16587953
TI  - Formalism for Conformal Geometry.

PMID- 16587954
TI  - Some Expansion Associated with Bessel Functions.

PMID- 16587955
TI  - New Varieties of Western Willows.

PMID- 16587956
TI  - The Oxygen Equilibrium of Hemoglobin and Its Structural Interpretation.

PMID- 16587957
TI  - The Rate and Extent of Anaerobic Decomposition of Sulfite Waste Liquor by
      Bacteria of Sea Bottom Mud: II. Bacteriological.

PMID- 16587958
TI  - Identification of the Salivary Gland Chromosomes in Drosophila Pseudoobscura.

PMID- 16587959
TI  - The Behavior of Unstable Genic Loci-An Hypothesis.

PMID- 16587960
TI  - Pollen-Tube Growth of a Translocation of the 1.2 Chromosome in Datura.

PMID- 16587961
TI  - Insectivora from the Sespe Uppermost Eocene, California.

PMID- 16587962
TI  - Application of Chain-Deformations to Critical Points and Extremals.

PMID- 16587963
TI  - Note on Pontrjagin's Topological Theorem of Duality.

PMID- 16587965
TI  - The Sensitive-Volume of the Meiotic Chromonemata of Gasteria as Determined by
      Irradiation with X-Rays.

PMID- 16587964
TI  - Connections between Differential Geometry and Topology.

PMID- 16587966
TI  - Movement of Sensory Hairs in the Ear.

PMID- 16587967
TI  - Panothenic Acid and the Nodule Bacteria-Legume Symbiosis.

PMID- 16587968
TI  - Lability of the Basal Metabolism of the Dairy Cow.

PMID- 16587970
TI  - Equatorial Longitude Effects on Cosmic Rays.

PMID- 16587969
TI  - The Provincetown, Massachusetts, Earthquake of April 23, 1935, and Data for
      Investigating New England's Seismicity.

PMID- 16587971
TI  - Spheroidal Functions of the Second Kind.

PMID- 16587972
TI  - Thermal Equilibrium in a General Gravitational Field.

PMID- 16587973
TI  - On the Expansion of Green's Function.

PMID- 16587975
TI  - Some Rare Amphibians and Reptiles of the United States.

PMID- 16587974
TI  - Studies of Carotenoid Pigments in Fishes: III. The Effects of Ingested
      Carotenoids upon the Xanthophyll Content of Fundulus Parvipinnis.

PMID- 16587976
TI  - Studies of Protective Color Change: III. Experiments with Fishes Both as
      Predators and Prey.

PMID- 16587978
TI  - The Automorphisms of Cayley's Non-Associative Algebra.

PMID- 16587977
TI  - Summation of Multiple Fourier Series by Spherical Means.

PMID- 16587979
TI  - On a Topological Characterization of Compact Convex Point Sets.

PMID- 16587980
TI  - Generalized Concavity Theorems.

PMID- 16587981
TI  - A Theorem of Extremals: II.

PMID- 16587982
TI  - A Certain Region in Euclidean 3-Space.

PMID- 16587983
TI  - On Normal Operators.

PMID- 16587985
TI  - The Effect of Yellow-Scute Gene Deficiency on Somatic Cells of Drosophila.

PMID- 16587984
TI  - Chromosome Ends in Datura Discolor.

PMID- 16587986
TI  - Headdot: An Incompletely Recessive White Spotting Character of the House Mouse.

PMID- 16587988
TI  - Linkage Studies of the Rat (Rattus Norvegicus).

PMID- 16587987
TI  - X Chromosome Inversions and Meiosis in Drosophila Melanogaster.

PMID- 16587989
TI  - X-Ray and Abnormalities: Increased Abnormality of Segments in Drosophila Due to X
      Raying of Gametes.

PMID- 16587990
TI  - The Ancestral Tree of the Proboscidea. Discovery, Evolution, Migration and
      Extinction Over a 50,000,000 Year Period.

PMID- 16587991
TI  - The Tempo of Growth of Fraternities.

PMID- 16587992
TI  - Analysis of 18,000 Proper Motions Derived at the Leander McCormick Observatory.

PMID- 16587993
TI  - Microincineration Studies: I. Localization of Inorganic Elements in Plant Cell
      Walls.

PMID- 16587994
TI  - Relation of Food to Regularity of Nutritional Response.

PMID- 16587995
TI  - Quadratic Wave Equation-Flood Waves in a Channel with Quadratic Friction.

PMID- 16587996
TI  - Maternal Effect as a Cause of the Difference between the Reciprocal Crosses in
      Drosophila Pseudoobscura.

PMID- 16587997
TI  - The Determination of Sex in Habrobracon.

PMID- 16587998
TI  - The Inheritance and Linkage Relations of Kinky Coat, a New Mutation in the Norway
      Rat.

PMID- 16587999
TI  - Titanothere Remains the Sespe of California.

PMID- 16588001
TI  - Sphere-Spaces.

PMID- 16588000
TI  - Differentiable Manifolds in Euclidean Space.

PMID- 16588002
TI  - Groups Which Are the Products of Two Permutable Proper Sub-Groups.

PMID- 16588004
TI  - On a Metric Property of Fuchsian Groups.

PMID- 16588003
TI  - Abstract Absolute Values Which Give New Irreducibility Criteria.

PMID- 16588005
TI  - Largest Groups Determined by the Squares of Their Operators.

PMID- 16588006
TI  - On Universal Homology Groups.

PMID- 16588007
TI  - A Conformal Wave Equation.

PMID- 16588008
TI  - The Kinetics of Penetration: X. Guanidine.

PMID- 16588009
TI  - The Correlation between Excess Calories and Excess Urinary Nitrogen in the
      Specific Dynamic Action of Protein in Animals.

PMID- 16588010
TI  - Relation of the Regulatory Mechanism of Respiration to Clinical Dyspnea.

PMID- 16588011
TI  - On Two Remarkable Ciliate Protozoa from the Caecum of the Indian Elephant.

PMID- 16588013
TI  - The Angular Diameters of Globular Clusters.

PMID- 16588012
TI  - A Study of 7900 External Galaxies.

PMID- 16588014
TI  - Increased Mutation Rate from Aged Datura Pollen.

PMID- 16588015
TI  - The Probability-Resultant.

PMID- 16588016
TI  - How to Use the Specific Formula of Heredity.

PMID- 16588017
TI  - The Problem of Dirichlet for an Ellipsoid.

PMID- 16588018
TI  - Three Theorems on the Envelop of Extremals.

PMID- 16588019
TI  - Groups of Order 2 Determined by Subgroups Generated by Their Squares.

PMID- 16588020
TI  - Sex-Modification in the Chick Embryo Resulting from Injections of Male and Female
      Hormones.

PMID- 16588021
TI  - Heights and Weights of 275 Public School Girls for Consecutive Ages 7 to 16
      Years, Inclusive.

PMID- 16588022
TI  - Transplantation of Fetal Tissues between Rabbits and Rats.

PMID- 16588023
TI  - The Torsion of a Circular Cylinder.

PMID- 16588024
TI  - Transplantation in Drosophila.

PMID- 16588025
TI  - The Temperature-Effective Period of the Scute-1 Phenotype.

PMID- 16588026
TI  - Pollen-Tube Growth of Ten Species of Datura in Interspecific Pollinations.

PMID- 16588027
TI  - Densities of Rocks Calculated from Their Chemical Analyses.

PMID- 16588028
TI  - The Ideal-Decomposition of Rational Primes in Terms of Absolute Values.

PMID- 16588029
TI  - On Pseudo-Linear Transformations.

PMID- 16588030
TI  - Formulas Giving the Number of the Groups Determined by Squares.

PMID- 16588031
TI  - On the Zeros of the Successive Derivatives of Integral Functions.

PMID- 16588032
TI  - Color Changes in Cancroid Crabs of Bermuda.

PMID- 16588033
TI  - Note on the Effect of Light on the Bioelectric Potentials in the Avena
      Coleoptile.

PMID- 16588034
TI  - Experiments on Young Chick Embryos Cultured in Vitro.

PMID- 16588035
TI  - Prismatic Deviation as a Function of Cosmical Orientation.

PMID- 16588036
TI  - Irradiation of Plant Viruses and of Microorganisms with Monochromatic Light: III.
      Resistance of the Virus of Typical Tobacco Mosaic and Escherichia Coli to
      Radiation from lambda 3000 to lambda 2250 A.

PMID- 16588037
TI  - Calcium as a Factor in the Nutritional Improvement of Health.

PMID- 16588038
TI  - Variegation in Drosophila and the Inert Chromosome Regions.

PMID- 16588040
TI  - Discontinuous Groups and Allied Topics: I.

PMID- 16588039
TI  - Special Regions of Regularity of Functions of Several Complex Variables.

PMID- 16588041
TI  - Discontinuous Groups and Allied Topics: II.

PMID- 16588042
TI  - A New Prehistoric Culture in Haiti.

PMID- 16588043
TI  - Concepts of Negative Degree.

PMID- 16588044
TI  - Extensions of Partially Ordered Sets.

PMID- 16588045
TI  - Further Studies of the Carotenoids of Two Pacific Marine Fishes, Fundulus
      Parvipinnis and Hypsypops Rubicunda, and of a Marine Annelid, Thoracophelia Sp.

PMID- 16588046
TI  - Color Changes in Elasmobranchs.

PMID- 16588047
TI  - Experimental and Clinical Study of Cobra Venom as an Analgesic.

PMID- 16588048
TI  - Structural Age Determination of Piedmont Intrusives in Maryland.

PMID- 16588049
TI  - Summary of Investigations of Variable Stars.

PMID- 16588050
TI  - Examples of Continuous Geometries.

PMID- 16588051
TI  - Complete Differential Systems.

PMID- 16588052
TI  - On General Manifolds.

PMID- 16588053
TI  - General Theorems Applying to All the Groups of Order 32.

PMID- 16588055
TI  - On the Explosiveness and Destructiveness of the 1918 Epidemic.

PMID- 16588054
TI  - Minimax Principle for Functions.

PMID- 16588056
TI  - Sespe Eocene Didelphids.

PMID- 16588057
TI  - The Biological Action of Neutron Rays.

PMID- 16588058
TI  - Relative Effectiveness of X-Rays and Fast Neutrons in Retarding Growth.

PMID- 16588059
TI  - On the Color of Crater Lake Water.

PMID- 16588060
TI  - The Visual Cycle and Protein Denaturation.

PMID- 16588061
TI  - Comparison of Statically and Dynamically Determined Young's Modulus of Rocks.

PMID- 16588062
TI  - Continuous Geometry.

PMID- 16588063
TI  - The Excess of Females among the Cree Indians.

PMID- 16588064
TI  - Anaerobic Fermentations of Sulphite Waste Liquor by Bacteria of Fresh Water Muds.

PMID- 16588065
TI  - The Magnetic Properties and Structure of the Hemochromogens and Related
      Substances.

PMID- 16588066
TI  - Segregation of Color and Growth-Regulating Genes in Somatic Tissue of Maize.

PMID- 16588067
TI  - Convergence Factors for Double Series Summable by Norlund Means.

PMID- 16588068
TI  - Functional Differential Equations and Inequalities.

PMID- 16588069
TI  - A Complete Characterization of the Derivative of a Polygenic Function.

PMID- 16588070
TI  - Hesperomeryx, a New Artiodactyl from the Sespe Eocene, California.

PMID- 16588071
TI  - Absorption of Cosmic Rays in the Milky Way.

PMID- 16588072
TI  - Observations on the Relation between Salivary Gland Chromosomes and Multiple
      Chromosome Complexes.

PMID- 16588073
TI  - Different Action of Auxin-A and of Heter-Auxin (Preliminary Note).

PMID- 16588074
TI  - The Double Motor Innervation of a Crayfish Muscle.

PMID- 16588076
TI  - Selective Absorption of Starlight by Interstellar Clouds.

PMID- 16588075
TI  - The Kinetics of Penetration: XIII. Effect of pH on the Entrance of Potassium into
      Nitella at Low Concentrations.

PMID- 16588077
TI  - On the Physical Condition of the Supernovae.

PMID- 16588078
TI  - A Model Imitating the Origin of Spiral Wall Structure in Certain Plant Cells.

PMID- 16588080
TI  - The System Albite-Fayalite.

PMID- 16588079
TI  - A New Red Alga from New Zealand.

PMID- 16588081
TI  - Frequency of "Cell-Lethals" among Lethals Obtained at Random in the X-Chromosome
      of Drosophila Melanogaster.

PMID- 16588082
TI  - Puberty in Eskimo Girls.

PMID- 16588084
TI  - Torsion of Rectangular Tubes.

PMID- 16588083
TI  - Eskimo Chronology.

PMID- 16588085
TI  - On the Problem of Plateau.

PMID- 16588086
TI  - On the Theory of Conformal Mapping.

PMID- 16588087
TI  - Regular Subgroups of a Transitive Substitution Group.

PMID- 16588088
TI  - Generalized Integrals and Differential Equations.

PMID- 16588089
TI  - On the Connectivity Ring of a Bicompact Space (Second Note).

PMID- 16588090
TI  - Phytopharmacological Reactions of Normal, Toxic and Atoxic Sera.

PMID- 16588091
TI  - Changing Direct Current to Alternating Current by Means of Thyratrons.

PMID- 16588092
TI  - Chimpanzee Metabolism.

PMID- 16588093
TI  - A Determination of the Magnitude of the Cell "Sensitive Volume" Associated with
      the White-Eye Mutation in X-Rayed Drosophila-: II.

PMID- 16588094
TI  - Dark Adaptation after Varying of Light Adaptation.

PMID- 16588095
TI  - Studies on the Body Temperature of Elephants.

PMID- 16588096
TI  - Differential Sensitivity in Sound Localization.

PMID- 16588097
TI  - On the Sensory Discrimination of Intensities.

PMID- 16588098
TI  - On Auditory Intensity Discrimination.

PMID- 16588099
TI  - Light Growth Response and Auxin Curvatures of Avena.

PMID- 16588100
TI  - Plant Tissue Cultures from a Hormone Point of View.

PMID- 16588101
TI  - Inhibition of Reinforcement' and Phenomena of Experimental Extinction.

PMID- 16588102
TI  - Demonstration of a Hatching Secretion in Rana Pipiens Schreber.

PMID- 16588103
TI  - Meteor Heights from the Arizona Expedition.

PMID- 16588104
TI  - Inter-Specific Hybrids in Platypoecilus: One Species ZZ-WZ; the Other XY-XX.

PMID- 16588106
TI  - Groups Containing a Relatively Large Number of Operators of the Same Order.

PMID- 16588105
TI  - Development of Eye Colors in Drosophila: Transplantation Experiments with
      Suppressor of Vermilion.

PMID- 16588107
TI  - Comparative Effects of X-Rays and Neutrons on Normal and Tumor Tissue.

PMID- 16588108
TI  - Characteristic Temperatures in Super-Novae.

PMID- 16588109
TI  - Interaction across Modalities: Simultaneous Stimulation.

PMID- 16588110
TI  - A Qualitative Study of the Bacterial Flora of Sea and Land Breezes.

PMID- 16588111
TI  - Genetic Effects of Ultra-Violet Radiation in Maize: I. Unfiltered Radiation.

PMID- 16588112
TI  - Genetic Effects of Ultra-Violet Radiation in Maize: II. Filtered Radiations.

PMID- 16588113
TI  - Genetic Effects of Ultra-Violet Radiation in Maize: III. Effects of Nearly
      Monochromatic lambda 2537, and Comparison of Effects of X-Ray and Ultra-Violet
      Treatment.

PMID- 16588114
TI  - A Terminal Inversion in Drosophila Ananassae.

PMID- 16588115
TI  - Observations on Mitosis in Opalinids (Protozoa, Ciliata): I. The Behavior and
      Individuality of Chromosomes and Their Significance.

PMID- 16588116
TI  - Observations on Mitosis in Opalinids (Protozoa, Ciliata): II. The Association of
      Chromosomes and Nucleoli.

PMID- 16588118
TI  - Intrinsic Properties of Light and Corpuscles from Distant Sources.

PMID- 16588117
TI  - Progressive Waves of Finite Amplitude and Some Steady Motions of an Elastic
      Fluid.

PMID- 16588119
TI  - Spectroscopic Absolute Magnitudes of Three Hundred and Seventy Southern Stars.

PMID- 16588120
TI  - Changes of Period in Variable Stars of Long Period.

PMID- 16588121
TI  - The Synthesis of Gamma-Methyl-5,6-Cyclopentenoretene, a Compound Structurally
      Related to "Diels' Hydrocarbon".

PMID- 16588122
TI  - The Intermediate Nucleus in the Disintegrative Synthesis of Atomic Nuclei:
      Disintegration in Steps.

PMID- 16588123
TI  - Reproductive Behavior and Haploid Parthenogenesis in the Grass Mite, Pediculopsis
      Graminum (Reut.) (Acarina, Tarsonemidae).

PMID- 16588124
TI  - The Genera of the Articulated Corallines.

PMID- 16588125
TI  - An Eocene Titanothere from San Diego County, California, with Remarks on the Age
      of the Poway Conglomerate.

PMID- 16588127
TI  - Linkage Studies of the Rat (Rattus Norvegicus): II.

PMID- 16588126
TI  - Relations between Chromosome Size and Effects of Inversions on Crossing-Over in
      Drosophila Melanogaster.

PMID- 16588128
TI  - The Coefficient of Prediction-Accuracy.

PMID- 16588129
TI  - Strength-Duration Curves and the Theory of Electrical Excitation.

PMID- 16588130
TI  - A Convergent Series for the Partition Function p(n).

PMID- 16588131
TI  - Note on the Curvature of Level Curves of Green's Function.

PMID- 16588132
TI  - Representations Induced in an Invariant Subgroup.

PMID- 16588133
TI  - On the Mean Value of r for Keplerian Systems.

PMID- 16588134
TI  - On the Equation of Diffusion.

PMID- 16588135
TI  - On the Statistical Theory of Turbulence.

PMID- 16588136
TI  - Chromosomal Deficiencies and the Embryonic Development of Drosophila
      Melanogaster.

PMID- 16588137
TI  - Deficiencies and Structural Variations within the Giant Chromosomes in Relation
      to the Problem of Gene Structure.

PMID- 16588138
TI  - Development of the Eye Colors in Drosophila: Extraction of the Diffusible
      Substances Concerned.

PMID- 16588139
TI  - Development of Eye Colors in Drosophila: Fat Bodies and Malpighian Tubes as
      Sources of Diffusible Substances.

PMID- 16588140
TI  - The Regeneration of Plate Rows in Mnemiopsis Leidyi, Agassiz.

PMID- 16588141
TI  - Immersion of the Fourier Transform in a Continuous Group of Functional
      Transformations.

PMID- 16588142
TI  - Lattices and Bicompact Spaces.

PMID- 16588143
TI  - Note on the Curvature of Orthogonal Trajectories of Level Curves of Green's
      Function.

PMID- 16588144
TI  - Iridophycus in the Northern Hemisphere.

PMID- 16588145
TI  - Effect of Auxin on Chlorella Vulgaris.

PMID- 16588146
TI  - On the Origin of Interstellar Radio Disturbances.

PMID- 16588147
TI  - New Evidence Pertaining to Puerto Rican Prehistory.

PMID- 16588148
TI  - Ionization Theory and Radio-Biological Reactions.

PMID- 16588149
TI  - Effects of the Length of X-Ray Waves on Seeds.

PMID- 16588150
TI  - Symmetry of the Transmission Coefficients for the Passage of Particles through
      Potential Barriers.

PMID- 16588151
TI  - Polymorphic Transitions of Inorganic Compounds to 50,000 kg./cm.

PMID- 16588153
TI  - Some Quantitative Relations between Visual Stimuli and the Production or
      Destruction of Melanin in Fishes.

PMID- 16588152
TI  - Color Changes Due to Erythrophores in the Squirrel Fish Holocentrus.

PMID- 16588154
TI  - A Remarkable Parallelism.

PMID- 16588155
TI  - The Relation of Gene to Character in Quantitative Inheritance.

PMID- 16588156
TI  - The Instantaneous Visual Threshold after Light Adaptation.

PMID- 16588157
TI  - The Groups of Order p Which Have m - 1 Independent Generators.

PMID- 16588158
TI  - On the Regular Representations of Algebras.

PMID- 16588159
TI  - Simple Lie Algebras of Type A.

PMID- 16588160
TI  - The Iterated Stieltjes Transform.

PMID- 16588161
TI  - Metric Methods in Calculus of Variations.

PMID- 16588162
TI  - Compressed Deficiency and the Location of the Spindle Attachment in the X
      Chromosome of Drosophila Pseudoobscura.

PMID- 16588163
TI  - Ovary Transplants in Drosophila Melanogaster: Meiosis and Crossing-Over in
      Superfemales.

PMID- 16588164
TI  - An Effect of the Y-Chromosome on the Sex-Ratio of Interracial Hybrids of
      Drosophila Pseudoobscura.

PMID- 16588165
TI  - The Effect of X-Rays on Chromosomes in Mitosis.

PMID- 16588166
TI  - The Action of Certain Substituted Phenols on Marine Eggs in Relation to Their
      Dissociation.

PMID- 16588167
TI  - The Production of Sterility in Male Mice by Irradiation with Neutrons.

PMID- 16588168
TI  - Sex, Sex Inheritance and Sex Determination in Paramecium Aurelia.

PMID- 16588169
TI  - Thiazole and the Growth of Excised Tomato Roots.

PMID- 16588170
TI  - Pyrimidine and Thiazole Intermediates as Substitutes for Vitamin B(1).

PMID- 16588171
TI  - The Structure of Langmuir-Blodgett Films of Stearic Acid.

PMID- 16588172
TI  - A Peccary Skull from the Barstow Miocene, California.

PMID- 16588174
TI  - Some Results in the Arithmetic Theory of Algebraic Functions of Several
      Variables.

PMID- 16588173
TI  - Note on Galactic Structure: The Milky Way from Aquila to Cygnus.

PMID- 16588175
TI  - Binary Quadratic Discriminants with a Single Class of Reduced Forms in Each
      Genus.

PMID- 16588177
TI  - Asymmetry of Light Curves in the Great Sequence as a Function of Frequency of
      Period.

PMID- 16588176
TI  - The Cancellation, Reinforcement and Measurement of Subjective Tones.

PMID- 16588178
TI  - The Present State of Our Knowledge Concerning the Life Cycle of the Foraminifera.

PMID- 16588179
TI  - Groups Having a Maximum Number Set of Independent Generators.

PMID- 16588180
TI  - Special Homology Groups.

PMID- 16588181
TI  - Log pi and Other Basic Constants.

PMID- 16588182
TI  - Einstein Spaces in a Space of Constant Curvature.

PMID- 16588183
TI  - Classification of Element Transformations by Means of Isogonal and Equi
      Tangential Series.

PMID- 16588184
TI  - Abstract Self-Adjoint Boundary Conditions.

PMID- 16588185
TI  - Note on the Stellar Distribution in the Vicinity of a Southern Galactic Window.

PMID- 16588186
TI  - A Simplified Method for Auxin Extraction.

PMID- 16588187
TI  - Light Intensity and the Nitrogen Hunger Period in the Manchu Soybean.

PMID- 16588188
TI  - The Continuumproblem.

PMID- 16588189
TI  - On the Existence of a Closed Convex Surface Realizing a Given Riemannian Metric.

PMID- 16588190
TI  - Organisms Requiring Vitamin B(1).

PMID- 16588191
TI  - A Cytological Study of Colchicine Effects in the Induction of Polyploidy in
      Plants.

PMID- 16588192
TI  - Chemical Stratification and Lake Morphology.

PMID- 16588193
TI  - Ascorbic Acid and the Growth of Plant Embryos.

PMID- 16588194
TI  - Potentials in Halicystis as Affected by Non-Electrolytes.

PMID- 16588195
TI  - A Comparison of the Diffusible Substances Concerned with Eye Color Development in
      Drosophila, Ephestia and Habrobracon.

PMID- 16588196
TI  - The Effect of pH on the Development of Ultra-Centrifuged Fucus Eggs.

PMID- 16588197
TI  - Chromosome Numbers in Nodules and Roots of Red Clover, Common Vetch and Garden
      Pea.

PMID- 16588198
TI  - Groups Having a Maximum Set of Independent Generators of the Same Order.

PMID- 16588199
TI  - Groups Having a Maximum Number Set of Conjugate Independent Generators.

PMID- 16588200
TI  - The Existence of a Minimal Surface of Least Area Bounded by Prescribed Jordan
      Arcs and Prescribed Surfaces.

PMID- 16588201
TI  - The Bar "Locus" and the v Reaction in Drosophila Melanogaster.

PMID- 16588202
TI  - Sex Reaction Types and Their Interrelations in Paramecium Bursaria: I.

PMID- 16588204
TI  - The Role of the Melanophore-Dispersing Hormone of the Pituitary in the Color
      Changes of the Catfish.

PMID- 16588203
TI  - Sex Reaction Types and Their Interrelations in Paramecium Bursaria: II. Clones
      Collected from Natural Habitats.

PMID- 16588205
TI  - On the Duplexity Theory of Visual Response in Vertebrates.

PMID- 16588206
TI  - On the Law for Minimal Discrimination of Intensities: III.

PMID- 16588207
TI  - A Determination of the Magnitude of the Cell "Sensitive Volume" Associated with
      the White-Eye Mutation in X-Rayed Drosophila: III.

PMID- 16588208
TI  - The Specificity of Pyrimidine for Phycomyces Blakesleeanus.

PMID- 16588209
TI  - The Specificity of Thiazole for Phycomyces Blakesleeanus.

PMID- 16588210
TI  - Note on the Problem of the Expanding Universe.

PMID- 16588211
TI  - Dependent Probabilities and Spaces (L).

PMID- 16588212
TI  - On Semi-Groups of Transformations in Hilbert Space.

PMID- 16588213
TI  - Residuated Lattices.

PMID- 16588214
TI  - Intersexuality in Drosophila Virilis and Its Bearing on Sex Determination.

PMID- 16588215
TI  - The Sedimentation Constant of Visual Purple.

PMID- 16588216
TI  - Biological Differences in the Action of Synthetic Male Hormones on the
      Differentiation of Sex in the Chick Embryo.

PMID- 16588217
TI  - The Generalized Clebsch-Gordan Formula.

PMID- 16588218
TI  - The Analysis of Representations of the Real Orthogonal Group.

PMID- 16588219
TI  - Natural Systems.

PMID- 16588220
TI  - Extensions of Measure.

PMID- 16588222
TI  - Evidence for a Second Thiamin.

PMID- 16588221
TI  - Representation and Equivalence of Forms.

PMID- 16588223
TI  - An Astacene-Like Carotenoid from a Pacific Coast Anemone, Epiactis Prolifera.

PMID- 16588224
TI  - The Structure of the Ring-Gland (Corpus Allatum) in Normal and Lethal Larvae of
      Drosophila Melanogaster.

PMID- 16588225
TI  - On Normal Division Algebras of Index 5.

PMID- 16588226
TI  - The Lift and Drag Functions for an Elastic Fluid in Two Dimensional Irrotational
      Flow.

PMID- 16588227
TI  - The Origin of Maize.

PMID- 16588228
TI  - Calculations of Bioelectric Potentials: III. Variation in Partition Coefficients
      and Ion Mobilities.

PMID- 16588229
TI  - Rayleigh Waves.

PMID- 16588230
TI  - Coulomb's Function.

PMID- 16588231
TI  - Functional Topology and Abstract Variational Theory.

PMID- 16588232
TI  - On Criteria Concerning Singular Integers in Cyclotomic Fields.

PMID- 16588233
TI  - Groups of Degree n Involving only Substitutions of Lower Degrees.

PMID- 16588234
TI  - On the Derivatives of Functions Analytic in the Unit Circle.

PMID- 16588236
TI  - Minimal Surfaces of Higher Topological Structure.

PMID- 16588235
TI  - Differential Calculus in Linear Topological Spaces.

PMID- 16588237
TI  - Green's Function and the Problem of Plateau.

PMID- 16588238
TI  - The Most General Form of the Problem of Plateau.

PMID- 16588239
TI  - Facet Number and the v Hormone in the Bar Eye of Drosophila Melanogaster.

PMID- 16588240
TI  - An X-Ray Induced Intercalary Duplication in Drosophila Involving Union of Sister
      Chromatids.

PMID- 16588242
TI  - The Mechanism of Delayed Killing of Maize Seeds with X-Radiation.

PMID- 16588241
TI  - The Distribution of Gene Frequencies in Populations of Polyploids.

PMID- 16588243
TI  - Contact Effects between Plant Roots and Soil Colloids.

PMID- 16588244
TI  - On Locally Connected Sets and Retracts.

PMID- 16588245
TI  - Conformal Geometry of Horn Angles of Second Order.

PMID- 16588247
TI  - Preliminary Report on Recent Geological and Archaeological Discoveries Relating
      to Early Man in Southeast Asia.

PMID- 16588246
TI  - A Skeleton Life Table.

PMID- 16588248
TI  - The Time Course of Photosynthesis as Shown by the Glass Electrode, with Anomalies
      in the Acidity Changes.

PMID- 16588249
TI  - The Time Course of Photosynthesis as Shown by a Rapid Electrode Method for
      Oxygen.

PMID- 16588251
TI  - Syntheses Carried Out in Vivo by Isolated Pea Roots: I.

PMID- 16588250
TI  - Reversal of the Potassium Effect in Nitella.

PMID- 16588252
TI  - Chromsome Phylogeny.

PMID- 16588253
TI  - Feather Characterization as Studied in Host-Graft Combinations Between Chick
      Embryos of Different Breeds.

PMID- 16588254
TI  - Concerning the Origin of the Polytene Chromosomes of Diptera.

PMID- 16588255
TI  - Some Effects of Light Intensity and Shade of Background Upon the Melanin Content
      of Gambusia.

PMID- 16588256
TI  - The Effects of Light and Dark Backgrounds Upon the Incidence of a Seemingly
      Infectious Disease in Fishes.

PMID- 16588257
TI  - Theory of Transversal Curves and the Connections Between the Calculus of
      Variations and the Theory of Partial Differential Equations.

PMID- 16588258
TI  - The Relative Numbers of the Subgroups and Operators of Certain Groups.

PMID- 16588259
TI  - On Interpolation and Approximation by Functions Analytic and Bounded in a Given
      Region.

PMID- 16588260
TI  - A New Foundation of Non-Euclidean, Affine, Real Projective and Euclidean
      Geometry.

PMID- 16588261
TI  - A Jordan Space Curve Having the Infinite Area Property at Each of Its Points.

PMID- 16588262
TI  - Partial Self-Incompatibility in Medicago Sativa.

PMID- 16588263
TI  - Mitotic Behavior of Induced Chromosomal Fragments Lacking Spindle Attachments in
      the Neuroblasts of the Grasshopper.

PMID- 16588264
TI  - A Titanothere from the Type Sespe of California.

PMID- 16588265
TI  - Autosomal Linkage in Man-The Recombination Ratio between Congenital Tooth
      Deficiency and Hair Color.

PMID- 16588266
TI  - Remarks on Plateau's and Douglas' Problem.

PMID- 16588267
TI  - Curvature Element Transformations Which Preserve Integrable Fields.

PMID- 16588268
TI  - Growth and Differentiation in Living Plant Meristems.

PMID- 16588269
TI  - Quantitative Analysis of the Interaction of Individuals.

PMID- 16588270
TI  - Astrophysical Consequences of Metastable Levels in Hydrogen and Helium.

PMID- 16588271
TI  - The Resolution of Six Tests into Three General Factors.

PMID- 16588273
TI  - Expressions for the Current in the Bloch Approximation of "Tight Binding" for
      Metallic Electrons.

PMID- 16588272
TI  - Temperature and the Critical Intensity for Response to Visual Flicker: II.

PMID- 16588274
TI  - The Oxidation-Reduction Potentials of Lake Waters and Their Ecological
      Significance.

PMID- 16588275
TI  - On Ideals of Differential Polynomials.

PMID- 16588276
TI  - Generalizations to Space of the Cauchy and Morera Theorems.

PMID- 16588277
TI  - An Equivalence Theorem for Series of Orthogonal Polynomials.

PMID- 16588278
TI  - The Occurrence of Parthenogenetic Diploids in Tetraploid Maize.

PMID- 16588279
TI  - The Synthesis and Destruction of Vitamin B(1) by Phycomyces.

PMID- 16588280
TI  - Temperature and the Critical Intensity for Response to Visual-Flicker: III. On
      the Theory of the Visual Response Contour, and the Nature of Visual Duplexity.

PMID- 16588281
TI  - Specific Constants for Visual Excitation: IV. On the Nature of Genetic
      Differences.

PMID- 16588282
TI  - A Note on Polarity Potentials from the Human Eye.

PMID- 16588283
TI  - Leaf Growth Factors II-The Activity of Pure Substances in Leaf Growth.

PMID- 16588284
TI  - Centrioles and Chromosomes in the Atypical Spermatogenesis of Vivipara.

PMID- 16588285
TI  - An Ergodic Theorem for n-Parameter Groups.

PMID- 16588287
TI  - General Self-Adjoint Boundary Conditions for Certain Partial Differential
      Operators.

PMID- 16588286
TI  - On Analogues of the Bernoulli and Allied Numbers.

PMID- 16588288
TI  - On the Gaussian Law of Errors in the Theory of Additive Functions.

PMID- 16588289
TI  - On the Connectivity Ring of a Lattice.

PMID- 16588290
TI  - Characterization of the Moebius Group of Circular Transformations.

PMID- 16588291
TI  - On the Intersections of Algebraic Differential Manifolds.

PMID- 16588292
TI  - The Plateau Problem for Non-Relative Minima.

PMID- 16588293
TI  - Consistency-Proof for the Generalized Continuum-Hypothesis.

PMID- 16588294
TI  - The Relation of the Eyes to the Integumentary Color Changes in the Catfish
      Ameiurus.

PMID- 16588295
TI  - The Nature of Chromosome Division and the Duration of the Nuclear Cycle.

PMID- 16588296
TI  - A Comparison of the Sensitivity of Mitotic and Meiotic Chromosomes of Vicia Faba
      and Its Bearing on Theories of Crossing-Over.

PMID- 16588297
TI  - The Magnetic Properties of the Compounds Ethylisocyanide-Ferrohemoglobin and
      Imidazole-Ferrihemoglobin.

PMID- 16588298
TI  - Crystalline Echinochrome and Spinochrome: Their Failure to Stimulate the
      Respiration of Eggs and of Sperm of Strongylocentrotus.

PMID- 16588299
TI  - The Finite Stieltjes Momentum Problem.

PMID- 16588300
TI  - The Non-Linear Boundary Value Problem of the Buckled Plate.

PMID- 16588301
TI  - Groups Which Contain Ten or Eleven Proper Subgroups.

PMID- 16588302
TI  - Linear Operations among Summable Functions.

PMID- 16588303
TI  - On a Method for Testing Linkage between Lethal Genes.

PMID- 16588304
TI  - The Gas Exchange of Drosophila Larvae.

PMID- 16588305
TI  - Scattering of Slow Neutrons by Protons.

PMID- 16588306
TI  - On the Formation of Clusters of Nebulae and the Cosmological Time Scale.

PMID- 16588308
TI  - Occurrence of Cretaceous Reptiles in the Moreno Shales of the Southern Coast
      Ranges, California.

PMID- 16588307
TI  - Bodily Constitution and Human Longevity.

PMID- 16588309
TI  - On Cauchy's Integral Theorem in the Real Plane.

PMID- 16588310
TI  - An Ergodic Theorem for General Semi-Groups.

PMID- 16588311
TI  - General Ergodic Theorems.

PMID- 16588312
TI  - Solution of the Inverse Problem of the Calculus of Variations.

PMID- 16588313
TI  - The Generality of Finite Abstract Complexes.

PMID- 16588314
TI  - Groups Having a Small Number of Sets of Conjugate Subgroups.

PMID- 16588316
TI  - Concerning Accessibility.

PMID- 16588315
TI  - The Algebraic Structure of Complexes.

PMID- 16588317
TI  - A New Inherited Character in Man.

PMID- 16588318
TI  - Influence of Female Stock on the Functioning of Small Pollen Male Gametes.

PMID- 16588319
TI  - Galactic and Extragalactic Studies: V. The Period Frequency of Classical Cepheids
      in the Magellanic Clouds.

PMID- 16588321
TI  - The Opacity of Extended Stellar Atmospheres.

PMID- 16588320
TI  - Remarks on Zwicky's Paper "On the Formation of Clusters of Nebulae and the
      Cosmological Time Scale".

PMID- 16588322
TI  - Normal Algebraic Number Fields.

PMID- 16588323
TI  - On an Ergodic Analysis of the Remainder Term of Mean Motions.

PMID- 16588324
TI  - Groups Which Contain Less Than Fourteen Proper Subgroups.

PMID- 16588325
TI  - On the Decomposition of Transitive Permutation Groups Generated by the Symmetric
      Group.

PMID- 16588326
TI  - General Expansion Theorems.

PMID- 16588327
TI  - Some Combinatorial Properties of Complexes.

PMID- 16588329
TI  - On the Synthesis of Cleavage Chromosomes.

PMID- 16588328
TI  - On the Theory of Sphere-Bundles.

PMID- 16588330
TI  - The Experimental Production of Melanin Pigment on the Lower Surface of Summer
      Flounders (Paralichthys Dentatus).

PMID- 16588331
TI  - A Respiratory Pigment from the Eggs of a Marine Worm.

PMID- 16588332
TI  - Further Studies on the Parthenogenetic Activation of Rabbit Eggs.

PMID- 16588333
TI  - Galactic and Extragalactic Studies: VI. Summary of a Photometric Survey of 35,000
      Galaxies in High Southern Latitudes.

PMID- 16588334
TI  - Studies in Calcium Metabolism with the Aid of Its Induced Radioactive Isotope: I.

PMID- 16588335
TI  - Some Biological Effects of Nuclear Disintegration Products on Neoplastic Tissue.

PMID- 16588336
TI  - A Decomposition of Compact Continua and Related Theorems on Fixed Sets under
      Continuous Transformations.

PMID- 16588337
TI  - Minimal Surfaces Spanning Closed Manifolds.

PMID- 16588338
TI  - On Cauchy's Integral Theorem and on the Law of the Mean for Non-Derivable
      Functions.

PMID- 16588339
TI  - Recalculation and Extension of the Modulus and of the Logarithms of 2, 3, 5, 7
      and 17.

PMID- 16588340
TI  - The Green's Function for a Differential System of Infinite Order.

PMID- 16588341
TI  - Theorems in the Inverse Problem in the Calculus of Variations.

PMID- 16588342
TI  - Cytoplasmic Behavior during Division of Vacuolate Plant Cells.

PMID- 16588343
TI  - Further Observations on the Mechanism of Induced Chromosome Rearrangement in
      Sciara.

PMID- 16588345
TI  - Polyploidy in Paramecium Bursaria.

PMID- 16588344
TI  - Conjugation of Three Animals in Paramecium Bursaria.

PMID- 16588346
TI  - Evidences of Exchange of Pronuclei during Conjugation in Paramecium Bursaria.

PMID- 16588347
TI  - Conjugation in Paramecium Bursaria between Animals with Very Different Chromosome
      Numbers and between Animals with and without Micronuclei.

PMID- 16588348
TI  - Novel Types of Nerve Reflexes.

PMID- 16588349
TI  - Agglutination of Sea-Urchin Eggs by Means of a Substance Extracted from the Eggs.

PMID- 16588350
TI  - Diurnal Variation of Intermedin in the Blood of the Albino Rat.

PMID- 16588351
TI  - The Absolute Magnitudes of Stars of High Luminosity.

PMID- 16588352
TI  - Synthetic Spectra for Supernovae.

PMID- 16588353
TI  - Micelle Formation in Aqueous Solutions of Digitonin.

PMID- 16588354
TI  - A Set of Postulates for Bolyai-Lobatchevsky Geometry.

PMID- 16588355
TI  - A General Theory of Spectra. I: I.

PMID- 16588356
TI  - The Groups Which Contain Exactly Fourteen Proper Subgroups.

PMID- 16588357
TI  - Equilong Symmetry with Respect to Any Curve.

PMID- 16588359
TI  - On the Distribution of Normal Point Groups.

PMID- 16588358
TI  - Partially Ordered Sets and Topology.

PMID- 16588360
TI  - The Effect of an "Emotional State" on the Initial Stages of Acquisition in a
      Conditioned Operant Response.

PMID- 16588361
TI  - Note on the Problem of the Distribution of Stress in a Thin Stiffened Elastic
      Sheet.

PMID- 16588362
TI  - On Some Periodic Properties of the System of Isotopes.

PMID- 16588363
TI  - Mechanism of Long Wave-Length Absorption of the Carbonyl Group.

PMID- 16588364
TI  - Mutations and Reversions in Reproductivity of Aspergilli with Nitrite, Colchicine
      and d-Lysine.

PMID- 16588365
TI  - A Comparison of Chromosomal Aberrations Induced by X-Ray and Ultra-Violet
      Radiation.

PMID- 16588366
TI  - Cytology and Development of the Embryos of X-Rayed Adult Drosophila Melanogaster.

PMID- 16588367
TI  - On the Law for Minimal Discrimination of Intensities: IV. DeltaI as a Function of
      Intensity.

PMID- 16588368
TI  - Differences between Men and Women in Their Response to Heat and Cold.

PMID- 16588369
TI  - On Possible Changes in the Solar "Constant".

PMID- 16588370
TI  - On Solar Faculae and Solar Constant Variations.

PMID- 16588371
TI  - The Course of Thiamin Metabolism in Man as Indicated by the Use of Radioactive
      Sulfur.

PMID- 16588372
TI  - Radioactive Carbon in the Study of Respiration in Heterotrophic Systems.

PMID- 16588373
TI  - CO(2) Assimilation by Propionic Acid Bacteria Studied by the Use of Radioactive
      Carbon.

PMID- 16588374
TI  - The Reduction of Radioactive Carbon Dioxide by Methane-Producing Bacteria.

PMID- 16588375
TI  - The Coronaviser, an Instrument for Observing the Solar Corona in Full Sunlight.

PMID- 16588376
TI  - A Pathological Case in the Numerical Solution of Integral Equations.

PMID- 16588377
TI  - The Conformal Theory of Curves.

PMID- 16588378
TI  - Traumatic Acid and Thiamin as Growth Factors for Algae.

PMID- 16588379
TI  - Some Trabeculate Codiums (Including Two New Species).

PMID- 16588380
TI  - Studies in Mineral Metabolism with the Aid of Induced Radioactive Isotopes: IV
      Manganese.

PMID- 16588381
TI  - A REVERSION TO WILD-TYPE ASSOCIATED WITH CROSSING-OVER IN DROSOPHILA
      MELANOGASTER.

PMID- 16588382
TI  - HD 167362, an Object Similar to Campbell's Hydrogen Envelope Star.

PMID- 16588383
TI  - The Spectrum of RW Hydrae.

PMID- 16588384
TI  - Compound Multiplicative Diophantine Systems.

PMID- 16588385
TI  - On Laguerre Series.

PMID- 16588386
TI  - Equilong and Conformal Transformations of Period Two.

PMID- 16588387
TI  - Radioactive Carbon as an Indicator of Carbon Dioxide Reduction: IV. The Synthesis
      of Acetic Acid from Carbon Dioxide by Clostridium Acidi-Urici.

PMID- 16588388
TI  - A Comparison of the Metabolism of Iodine and of Element 85 (Eka-Iodine).

PMID- 16588389
TI  - Surfaces of Minimal Capacity.

PMID- 16588390
TI  - The Polynomial of Mittag-Leffler.

PMID- 16588392
TI  - Subgroups of the Groups Whose Orders Are Below Thirty.

PMID- 16588391
TI  - Binary Forms.

PMID- 16588393
TI  - A General Theorem on Conformal Mapping of Multiply Connected Domains.

PMID- 16588394
TI  - Ribonucleic Acids in Both Nucleus and Cytoplasm, and the Function of the
      Nucleolus.

PMID- 16588395
TI  - THE GENETIC CONTROL OF NUCLEOLAR COMPOSITION.

PMID- 16588396
TI  - ARE DIFFERENCES IN SIZE BETWEEN PARTS OF THE BODY DUE TO GENERAL OR SPECIFIC
      FACTORS?

PMID- 16588397
TI  - A PENTAPLOID LARVA OF THE NEWT, TRITURUS VIRIDESCENS.

PMID- 16588398
TI  - UNEQUAL BREAKS IN TWO SISTER CHROMATIDS INDUCED BY X-RAYS IN DROSOPHILA
      MELANOGASTER.

PMID- 16588399
TI  - A Note on the Variation of Delta Scuti.

PMID- 16588400
TI  - Galactic and Extragalactic Studies: VIII. A New Determination of the Period
      Luminosity Curve.

PMID- 16588401
TI  - The Spectrum of BD +30 degrees 3639.

PMID- 16588402
TI  - Galactic and Extragalactic Studies: IX. A Photometric Survey of 22,000 Galaxies
      in the Zone from delta = +41 degrees to delta = +46 degrees.

PMID- 16588403
TI  - Inhibition of Carboxylase by Thiazole Pyrophosphate.

PMID- 16588404
TI  - On Homotopy Groups.

PMID- 16588405
TI  - On a General Rule Concerning the Half-Value Periods of Electron-Emitting Nuclei.

PMID- 16588406
TI  - THE EFFECT OF FAST NEUTRONS ON THE CHROMOSOMES OF TRADESCANTIA.

PMID- 16588407
TI  - CHROMOSOME HOMOLOGIES IN TWO SUB-SPECIES OF DROSOPHILA VIRILIS.

PMID- 16588408
TI  - LINKAGE STUDIES OF THE RAT (RATTUS NORVEGICUS): III.

PMID- 16588409
TI  - Synthesis of Thiamin by Excised Roots of Maize.

PMID- 16588410
TI  - The Development of Melanophores from Embryonic Mouse Tissues Grown in the Coelom
      of Chick Embryos.

PMID- 16588411
TI  - Galactic and Extragalactic Studies: XI. Note on the Period-Frequency of Galactic
      Cepheids.

PMID- 16588412
TI  - The Absorption of Bicarbonate Ion by Barley Plants as Indicated by Studies with
      Radioactive Carbon.

PMID- 16588413
TI  - A Remark on General Fuchsian Groups.

PMID- 16588414
TI  - The Distance in General Fuchsian Geometries.

PMID- 16588416
TI  - Unstable Minimal Surfaces of Higher Topological Types.

PMID- 16588415
TI  - Abstract Definite Boundary Value Problems.

PMID- 16588418
TI  - The Twelfth Primary Trisomic Type in Nicotiana Sylvestris.

PMID- 16588417
TI  - Purine and Pyrimidine as Growth Substances for Lactic Acid Bacteria.

PMID- 16588419
TI  - Isolating Mechanisms in Tree Frogs.

PMID- 16588420
TI  - The Time Interval between X-Radiation of Sperm of Drosophila and Chromosome
      Recombination.

PMID- 16588421
TI  - Mechanism of the Origin of X-Ray Induced Notch Deficiencies in Drosophila
      Melanogaster.

PMID- 16588422
TI  - Another Case of Unequal Crossing-Over in Drosophila Melanogaster.

PMID- 16588423
TI  - Position of Adult Testes in Drosophila Melanogaster Meigen.

PMID- 16588424
TI  - An Analysis of X-Ray Induced Single Breaks in Neuroblast Chromosomes of the
      Grasshopper (Chortophaga Viridifasciata).

PMID- 16588425
TI  - Discovery of a Predicted Gene Arrangement in Drosophila Azteca.

PMID- 16588426
TI  - Critical Points and Unstable Minimal Surfaces.

PMID- 16588427
TI  - A Note on Conformal Geometry.

PMID- 16588428
TI  - Homotopy Relations in Fibre Spaces.

PMID- 16588429
TI  - Note on Linear Difference and Differential Equations.

PMID- 16588430
TI  - Maximal Subgroups of a Given Group.

PMID- 16588431
TI  - Contact and Measles.

PMID- 16588432
TI  - A Unified Theory of Integration.

PMID- 16588433
TI  - On Improperly Irregular Cyclotomic Fields.

PMID- 16588434
TI  - A General Theory of Spectra: II.

PMID- 16588435
TI  - General Invariants of Irregular Analytic Elements.

PMID- 16588436
TI  - A New Form of Culture on the Arctic Coast.

PMID- 16588437
TI  - Effects of Eye-Stalk Removal on Decapod Crustaceans.

PMID- 16588438
TI  - The Oxidation of Estrogens by Phenolases.

PMID- 16588439
TI  - Studies in Mineral Metabolism with the Aid of Artificial Radioactive Isotopes:
      VI. Cobalt.

PMID- 16588440
TI  - The Isolation in Culture of Grahamellae from Various Species of Small Rodents.

PMID- 16588441
TI  - Mechanism of Biological Nitrogen Fixation: VI. Inhibition of Azotobacter by
      Hydrogen.

PMID- 16588442
TI  - Notes on Binary Stars: IV. A Source of Spurious Eccentricity in Spectroscopic
      Binaries.

PMID- 16588443
TI  - Notes on Binary Stars: V. The Determination by Least-Squares of the Elements of
      Spectroscopic Binaries.

PMID- 16588444
TI  - On Real Closed Curves of Order n + 1 in Projective n-Space.

PMID- 16588445
TI  - Concerning Relatively Non-Alternating Transformations.

PMID- 16588447
TI  - Existence, Convergence and Equivalence in the Unified Theory of Eigenvalues of
      Plates and Membranes.

PMID- 16588446
TI  - The Minimal Number Problem of Binary Forms.

PMID- 16588448
TI  - Two Interesting Nuclei of Planetary Nebulae: IC 418 and NGC 40.

PMID- 16588449
TI  - Radioactive Carbon as an Indicator of Carbon Dioxide Utilization: V. Studies on
      the Propionic Acid Bacteria.

PMID- 16588451
TI  - On the First Variation of the Dirichlet-Douglas Integral and on the Method of
      Gradients.

PMID- 16588450
TI  - Relation between Genes and Carotenoids of the Tomato.

PMID- 16588452
TI  - Dominant vs. Recessive Lethal Mutation.

PMID- 16588453
TI  - Linkage Studies of the Rat (Rattus Norvegicus): IV.

PMID- 16588454
TI  - The Effect of Adult Body Color Mutations upon the Larva of Drosophila
      Melanogaster.

PMID- 16588455
TI  - The Spermatophores of Triturus Torosus and Triturus Rivularis.

PMID- 16588456
TI  - On a Cluster of Nebulae in Hydra.

PMID- 16588457
TI  - Enzymes in Ontogenesis: XVI. Activation of Protyrosinase by Sodium Alkyl
      Sulfates.

PMID- 16588458
TI  - Field Properties of the Developing Frog's Egg.

PMID- 16588459
TI  - Invariant Forms of Interaction between Nuclear Particles.

PMID- 16588460
TI  - Riboflavin Contents of Tissues as Stabilized in the Adult at Liberal Levels of
      Intake.

PMID- 16588461
TI  - The Physico-Chemical Structure of the Salivary Gland Chromosomes: II.

PMID- 16588463
TI  - A Generalization of the Euclidian Algorithm to Several Dimensions.

PMID- 16588462
TI  - Certain Singular Points on Crystallization Curves of Solid Solutions.

PMID- 16588464
TI  - On the Problem of Analyticity in Dynamics.

PMID- 16588465
TI  - A Generalization of Frechet's Differential.

PMID- 16588466
TI  - A Generalization of the Dirac Equations.

PMID- 16588467
TI  - Generalization of Completely Convex Functions.

PMID- 16588469
TI  - The Method of the Minimum Integral and Analytic Continuation of Functions of
      Complex Variables.

PMID- 16588468
TI  - Natural Systems: The Structure of Abstract Monotone Sequences.

PMID- 16588470
TI  - The Form of Gaseous Configurations Rotating with Non-Uniform Angular Velocity.

PMID- 16588471
TI  - Remarks on the Pegasus Cluster of Nebulae.

PMID- 16588472
TI  - The Inactivation of Bacteriophages by X-Rays-Influence of the Medium.

PMID- 16588473
TI  - Binghamia, The Alga, versus Binghamia, the Cactus.

PMID- 16588474
TI  - Growth Regulators of Plants and Formative Effects Induced with beta-Naphthoxy
      Compounds.

PMID- 16588475
TI  - The Effects of Wounding and Wound Hormones on Root Formation.

PMID- 16588476
TI  - Sterility in Crosses of Geographical Races of Drosophila Micromelanica.

PMID- 16588477
TI  - Linkage Studies of the Rat (Rattus Norvegicus): V.

PMID- 16588478
TI  - Maximal Subgroups Whose Orders Are Divisible by Two or Three.

PMID- 16588479
TI  - Metric Foundations of Geometry.

PMID- 16588480
TI  - Lineal Element Transformations Which Preserve the Isothermal Character.

PMID- 16588481
TI  - Lineal Element Transformations Which Preserve the Dual-Isothermal Character.

PMID- 16588482
TI  - Non-Linear Equations of the Electromagnetic Field.

PMID- 16588483
TI  - Distorted Equilibrium Configuration of a Perfect Compressible Fluid Mass.

PMID- 16588484
TI  - Some Lethal Effects of Ultra-Violet Radiation of Fungus Spores.

PMID- 16588485
TI  - Prolycopene, a Naturally Occuring Stereoisomer of Lycopene.

PMID- 16588486
TI  - Radioactive Carbon as an Indicator of Carbon Dioxide Utilization: VI. On the
      Possibility of Carbon Dioxide Reduction via the Carboxylase System.

PMID- 16588487
TI  - Visibility of the Primary Spindle Fibres and the Course of Mitosis in the Living
      Blastomeres of the Mite, Pepiculopsis Graminum (Reut.).

PMID- 16588488
TI  - Germ Cell Movements and Sex Differentiation of the Gonads in the Drosophila
      Embryo.

PMID- 16588489
TI  - On the Independence of Line Integrals on the Path.

PMID- 16588490
TI  - Terminal Adhesions of Salivary Gland Chromosomes in Drosophila.

PMID- 16588491
TI  - An Experiment in Olfactory Conditioning in Drosophila Guttifera.

PMID- 16588492
TI  - Genetic Control of Biochemical Reactions in Neurospora.

PMID- 16588493
TI  - The Frequency of Polyploidy and Other Spontaneous Aberrations of Chromosome
      Number among Larvae of the Newt, Triturus Viridescens.

PMID- 16588494
TI  - A White-flowered Race of Datura Which is Genetically Distinct.

PMID- 16588495
TI  - Genetic Linkage in the Rabbit.

PMID- 16588496
TI  - Formation and Reduction of Indophenol Blue in Development of an Echinoderm.

PMID- 16588497
TI  - The Provitamin A Content of American Whole Wheat Flour and Whole Wheat Bread.

PMID- 16588498
TI  - Metric Conditions for Symmetric Finsler Spaces.

PMID- 16588499
TI  - Infinite Cycles and Homologies.

PMID- 16588500
TI  - Some Properties of Real Linear Topological Spaces.

PMID- 16588501
TI  - The Concept of Ecospecies in Tertiary Paleobotany.

PMID- 16588502
TI  - Patterns of Growth in Human Intelligence.

PMID- 16588503
TI  - Intersexes in Drosophila Pseudoobscura.

PMID- 16588504
TI  - The Origin of Jerker, a New Gene Mutation of the House Mouse, and Linkage Studies
      Made with It.

PMID- 16588505
TI  - Genic Effects on Serum Proteins.

PMID- 16588506
TI  - On the Motion of Vortices in Two Dimensions: I. Existence of the Kirchhoff-Routh
      Function.

PMID- 16588507
TI  - On the Motion of Vortices in Two Dimensions: II. Some Further Investigations on
      the Kirchhoff-Routh Function.

PMID- 16588509
TI  - The Generation of Inseparable Fields.

PMID- 16588508
TI  - Concerning the Differential Equations of Some Boundary Layer Problems.

PMID- 16588510
TI  - Maximal Invariant Proper Subgroups of a Finite Group.

PMID- 16588511
TI  - Radioactive Carbon as an Indicator of Carbon Dioxide Utilization: VII. The
      Assimilation of Carbon Dioxide by Molds.

PMID- 16588513
TI  - Representation of Measurable Flows in Euclidean 3-Space.

PMID- 16588512
TI  - Prehistoric Contact between South America and the West Indies.

PMID- 16588514
TI  - Inversion of a Generalized Laplace Integral.

PMID- 16588515
TI  - On Formal Exponential Differentiation in Rings.

PMID- 16588516
TI  - Guanine and Factor Z(1), Growth Substances for Phycomyces.

PMID- 16588517
TI  - Radioactive Carbon as an Indicator of Carbon Dioxide Utilization: VIII. The Role
      of Carbon Dioxide in Cellular Metabolism.

PMID- 16588519
TI  - Comparative Rates of Division in Large and Small Cells of Developing Fruits.

PMID- 16588518
TI  - Relative Effects of X-Rays and Neutrons on Chromosomes in Different Parts of the
      "Resting Stage".

PMID- 16588520
TI  - Chromosome Degeneration in Relation to Growth and Hybrid Vigor.

PMID- 16588522
TI  - A General Theorem on the Initial Curvature of Dynamical Trajectories.

PMID- 16588521
TI  - Temperature and "Sex-Ratio" in Drosophila Pseudoobscura.

PMID- 16588523
TI  - Generalized Transformation Theory of Isothermal and Dual Families.

PMID- 16588524
TI  - Concerning Separability.

PMID- 16588525
TI  - The Coefficients of Stirling's Series for Log Gamma(x).

PMID- 16588526
TI  - Oscillations of the Derivatives of a Function.

PMID- 16588528
TI  - "Ataxia," a Hereditary Nervous Disorder of the Rabbit.

PMID- 16588527
TI  - An Autosomal Recessive Factor Inducing Semi-Sterility in Drosophila Melanogaster
      Females.

PMID- 16588529
TI  - The Identification and Characterization of Bacteriophages with the Electron
      Microscope.

PMID- 16588530
TI  - Concentration of Growth Hormone and Fruitfulness in the Montmorency Cherry.

PMID- 16588531
TI  - The Calculation of Rotation Factors for Eclipsing Binary Systems.

PMID- 16588532
TI  - Certain Direct Products of the Groups of Self-Isometries.

PMID- 16588533
TI  - Certain Congruence Criteria Connected with Fermat's Last Theorem.

PMID- 16588534
TI  - On the Physical Characteristics of the Hydra Cluster of Nebulae.

PMID- 16588535
TI  - Radioactive Carbon as an Indicator of Carbon Dioxide Utilization: IX. The
      Assimilation of Carbon Dioxide by Protozoa.

PMID- 16588536
TI  - The Energy Equation for a Viscous Compressible Fluid.

PMID- 16588537
TI  - Sensitization of Melanophores by Nerve Cutting.

PMID- 16588538
TI  - On Generalized Biorthogonal Expansions in Metric and Unitary Spaces.

PMID- 16588539
TI  - Representation of One-Parameter Semi-Groups of Linear Transformations.

PMID- 16588540
TI  - On a Class of Surfaces.

PMID- 16588541
TI  - Galactic and Extragalactic Studies: XIII. Note on the Comparative Diameters of
      Spheroidal and Spiral Galaxies.

PMID- 16588542
TI  - Galactic and Extragalactic Studies: XIV. On the Magnitude Dispersion in the
      Period-Luminosity Relation.

PMID- 16588543
TI  - Galactic and Extragalactic Studies: XV. On the Distribution of Periods for 343
      Cepheids in the Small Magellanic Cloud.

PMID- 16588544
TI  - Close Linkage between Mutations with Similar Effects.

PMID- 16588545
TI  - The Effect of pH on Inactivation of Tobacco Mosiac Virus by X-Rays.

PMID- 16588546
TI  - Diffusion of Gene Products.

PMID- 16588547
TI  - The Effect of X-Ray Stimulation on the Bioelectric Potentials of the Avian Egg.

PMID- 16588548
TI  - Nucleic Acid Storage in the Toad's Egg.

PMID- 16588549
TI  - On the Perseus Cluster of Nebulae.

PMID- 16588550
TI  - A Reversible Growth Inhibition of Isolated Tomato Roots.

PMID- 16588551
TI  - General Congruences Involving the Bernoulli Numbers.

PMID- 16588552
TI  - Transformation Theory of Isogonal Trajectories of Isothermal Families.

PMID- 16588553
TI  - Differential Equations of the Type: y''' = Gy'' + Hy''.

PMID- 16588554
TI  - Oxidation-Reduction Patterns in Amphibian and Teleost Development.

PMID- 16588555
TI  - Nucleoproteins of Cell Nuclei.

PMID- 16588556
TI  - A Pyrimidine Analog of Thiamine and the Growth of Fungi.

PMID- 16588557
TI  - On the Physical Characteristics of the Perseus Cluster of Nebulae.

PMID- 16588558
TI  - The Epidemic Curve.

PMID- 16588559
TI  - Automorphisms of the Dihedral Groups.

PMID- 16588560
TI  - Some Asymptotic Relations.

PMID- 16588562
TI  - Contingency Tables.

PMID- 16588561
TI  - An Orthogonal Property of the Hypergeometric Polynomial.

PMID- 16588563
TI  - The Association of Three Attributes.

PMID- 16588564
TI  - A Complement-Release Reaction; The Neutralization of the Anticomplementary Action
      of Sea-Urchin Fertilizin by Antifertilizin.

PMID- 16588565
TI  - White Pigmentary Effectors (Leucophores) in Killifishes.

PMID- 16588566
TI  - Distortion of Stratigraphic Thicknesses Due to Folding.

PMID- 16588568
TI  - The Structure of Algebraic Moduls.

PMID- 16588567
TI  - The Permutation Groups of a General Degree.

PMID- 16588569
TI  - Synthetic Solution of the Inverse Problem of Dynamics.

PMID- 16588570
TI  - On the Theory of Analytic Curves.

PMID- 16588571
TI  - On the Analytical Theory of Semi-Groups.

PMID- 16588572
TI  - Generalization of Sundman's Fundamental Equality to the Case of More Than Three
      Bodies.

PMID- 16588573
TI  - Generalization of the Inequality of Sundman to the Case of More Than Three Bodies
      and to the Case of a Gravitational Gas.

PMID- 16588574
TI  - On the Anaphase Movement of Chromosomes.

PMID- 16588575
TI  - Heat-Induced Triploidy in the Newt, Triturus Viridescens.

PMID- 16588576
TI  - The Increase of B Vitamins in Germinating Seeds.

PMID- 16588577
TI  - Notes on Algal Nomenclature: I. Pollexfenia, Jeannerettia and Mesotrema.

PMID- 16588578
TI  - Sexual Hormones in Achlya: V. Hormone A', a Male-Secreted Augmenter or Activator
      of Hormone A.

PMID- 16588579
TI  - Oxidized Cotton, an Immunologically Specific Polysaccharide.

PMID- 16588580
TI  - The Genetic Nature of X-Ray Induced Changes in Pollen.

PMID- 16588581
TI  - The Lower Hydrates of Soap.

PMID- 16588582
TI  - The Characteristics of Soap Hemihydrate Crystals.

PMID- 16588583
TI  - Statistical Metrics.

PMID- 16588584
TI  - Natural Isomorphisms in Group Theory.

PMID- 16588585
TI  - Concerning Intersecting Continua.

PMID- 16588586
TI  - Concerning a Continuum and Its Boundary.

PMID- 16588587
TI  - Concerning Domains Whose Boundaries Are Compact.

PMID- 16588588
TI  - On Sets of Integers Which Contain No Three Terms in Arithmetical Progression.

PMID- 16588589
TI  - Some Advances in the Combinatory Theory of Quantification.

PMID- 16588590
TI  - Chromosome Ends in Datura Pruinosa.

PMID- 16588591
TI  - Mechanism of Induction of Gross Chromosomal Rearrangements in Drosophila Sperms.

PMID- 16588592
TI  - The Effect of Centrifuging Upon the Production of X-Ray Induced Chromosomal
      Aberrations.

PMID- 16588593
TI  - Increase in Mammary Carcinoma Incidence Following Inoculations of Whole Blood.

PMID- 16588594
TI  - Determination of the Subgroups of Small Index.

PMID- 16588595
TI  - Existence of Periodic Solutions for Certain Differential Equations.

PMID- 16588596
TI  - On the Euclidean Connections in a Finsler Space.

PMID- 16588597
TI  - A Generalization of the Projective Geometry of Linear Spaces.

PMID- 16588598
TI  - The Epidemic Curve: II.

PMID- 16588600
TI  - Possible Groups of Automorphisms.

PMID- 16588599
TI  - A Complex Induced Rearrangement of Drosophila Chromosomes and Its Bearing on the
      Problem of Chromosome Recombination.

PMID- 16588601
TI  - Fixed Elements and Periodic Types for Homeomorphisms on S. L. C. Continua.

PMID- 16588602
TI  - Atropinesterase, a Genetically Determined Enzyme in the Rabbit.

PMID- 16588603
TI  - Note on the Time-Intensity Factor in Radiobiology.

PMID- 16588604
TI  - Some Interrelationships of Pyridoxine, Alanine and Glycine in Their Effect on
      Certain Lactic Acid Bacteria.

PMID- 16588605
TI  - Strain Specificity and Production of Antibiotic Substances.

PMID- 16588606
TI  - The Determination of L.D.50 and Its Sampling Error in Bio-Assay.

PMID- 16588607
TI  - Mastophora and the Mastophoreae: Genus and Subfamily of Corallinaceae.

PMID- 16588608
TI  - The Pedigreed Culture of Paramecium Aurelia at Yale University.

PMID- 16588609
TI  - High Mutation Frequency in Drosophila Pseudoobscura, Race B.

PMID- 16588611
TI  - Bio-Assay on a General Curve.

PMID- 16588610
TI  - On the Physical Basis for Genetic Resistance to Mouse Typhoid, Salmonella
      Typhimurium.

PMID- 16588612
TI  - Relations between Homology and Homotopy Groups.

PMID- 16588613
TI  - A Stress Function for the Membrane Theory of Shells of Revolution.

PMID- 16588614
TI  - Colchicine-Induced Allo- and Autopolyploidy in Nicotiana.

PMID- 16588615
TI  - Chromosomal Aberrations in Brazilian Drosophila Ananassae.

PMID- 16588617
TI  - Special Invariant Subgroups.

PMID- 16588616
TI  - A New Method for Hybridizing Yeast.

PMID- 16588618
TI  - Subgroups Transformed According to a Group of Prime Order.

PMID- 16588619
TI  - On Convex Topological Linear Spaces.

PMID- 16588620
TI  - Natural Logarithms of Small Prime Numbers.

PMID- 16588621
TI  - Genic Induction of an Inherited Cytoplasmic Difference.

PMID- 16588622
TI  - Gene and Cytoplasm: I. The Determination and Inheritance of the Killer Character
      in Variety 4 of Paramecium Aurelia.

PMID- 16588623
TI  - Gene and Cytoplasm: II. The Bearing of the Determination and Inheritance of
      Characters in Paramecium Aurelia on the Problems of Cytoplasmic Inheritance,
      Pneumococcus Transformations, Mutations and Development.

PMID- 16588624
TI  - The Relation between Number of Nucleoli and Number of Chromosome Sets in Animal
      Cells.

PMID- 16588625
TI  - On Primary Attributes of Alleles in Drosophila Melanogaster.

PMID- 16588626
TI  - On Wild-Type Iso-Alleles in Drosophila Melanogaster.

PMID- 16588628
TI  - A Type of Universal Arithmetical Forms.

PMID- 16588627
TI  - Chromosome Complements of Some South-Brazilian Species of Drosophila.

PMID- 16588629
TI  - The Apollonian Packing of Circles.

PMID- 16588631
TI  - Concerning Webs in the Plane.

PMID- 16588630
TI  - Concerning Continua Which Have Dendratomic Subsets.

PMID- 16588632
TI  - Efficient Computation of the Latent Vectors of a Matrix.

PMID- 16588633
TI  - A Simple Method of Interpolation.

PMID- 16588634
TI  - The Effect of X-Rays upon Dominant Mutation in Maize.

PMID- 16588635
TI  - Graphical Method of Factoring the Correlation Matrix.

PMID- 16588637
TI  - Remark on a Distortion Tensor for Elastic Displacements.

PMID- 16588636
TI  - The Development of Normal and Homozygous Brachy (T/T) Mouse Embryos in the
      Extraembryonic Coelom of the Chick.

PMID- 16588638
TI  - The Minimum Rank of a Correlation Matrix.

PMID- 16588639
TI  - A Specific Abnormality Associated with a Variety of Genotypes.

PMID- 16588640
TI  - Can Specific Mutations Be Induced by Serological Methods?

PMID- 16588641
TI  - The Induction of Mutations by Antibodies.

PMID- 16588642
TI  - A Reconsideration of the Mechanism of Position Effect.

PMID- 16588643
TI  - Materials for the Study of the Position Effect of Normal and Mutant Genes.

PMID- 16588644
TI  - Comparison of a Degenerate Form of Einstein's with Birkhoff's Theory of
      Gravitation.

PMID- 16588645
TI  - Scale Curves in General Cartography.

PMID- 16588646
TI  - Genetic Linkage of Blood Types in the Rabbit.

PMID- 16588647
TI  - Concerning Linkage of Waltzing in Rats.

PMID- 16588648
TI  - Linkage of Waltzing in the Rat.

PMID- 16588649
TI  - X-Ray Inhibition of Mitosis in Relation to Chromosome Number.

PMID- 16588650
TI  - Experiments on Sexual Isolation in Drosophila: I. Geographic Strains of
      Drosophila Willistoni.

PMID- 16588651
TI  - The Compressibility of Media under Extreme Pressures.

PMID- 16588652
TI  - Note on the Discovery of Red Stars.

PMID- 16588653
TI  - Antibiotic Activity of Lichens.

PMID- 16588654
TI  - Activity and Nutritional Deprivation.

PMID- 16588655
TI  - The Epidemic Curve with No Accession of Susceptibles.

PMID- 16588656
TI  - Integral Formulas for the Characteristic Classes of Sphere Bundles.

PMID- 16588657
TI  - On Groups of Automorphism of Lie Groups.

PMID- 16588658
TI  - Groups Containing Less Than Twenty-Eight Non-Invariant Operators.

PMID- 16588659
TI  - A Group-Theoretic Characterization of the General Projective Collineation Group.

PMID- 16588660
TI  - Experiments on Sexual Isolation in Drosophila: III. Geographic Strains of
      Drosophila Sturtevanti.

PMID- 16588661
TI  - Experiments on Sexual Isolation in Drosophila: II. Geographic Strains of
      Drosophila Prosaltans.

PMID- 16588662
TI  - Mendelian Inheritance of Adaptive Enzymes.

PMID- 16588663
TI  - Apomixis in Guayule.

PMID- 16588664
TI  - A Method in Rational Diophantine Analysis.

PMID- 16588665
TI  - Groups Involving a Small Number of Sets of Conjugate Operators.

PMID- 16588666
TI  - Some Theorems in Finite Field Theory with Applications to Fermat's Last Theorem.

PMID- 16588667
TI  - On Trinomial Congruences and Fermat's Last Theorem.

PMID- 16588668
TI  - On the Integral Equations of Continuous Dynamical Systems.

PMID- 16588669
TI  - The Mechanism of Bioluminescence.

PMID- 16588670
TI  - On the Theory of the Tension of an Elastic Cylinder.

PMID- 16588671
TI  - The Synapsis of the Sex Chromosomes of Drosophila Miranda in Relation to Their
      Directed Segregation.

PMID- 16588672
TI  - Visible Expression of Cytoplasmic Pattern in the Differentiation of Xylem
      Strands.

PMID- 16588673
TI  - A Growth-Delaying Effect of Ultraviolet Radiation.

PMID- 16588674
TI  - Incidence of Metabolic Changes among Virus-Resistant Mutants of a Bacterial
      Strain.

PMID- 16588675
TI  - X-Ray Induced Growth Factor Requirements in Bacteria.

PMID- 16588676
TI  - The Amounts of Acetylcholine in the Dark Skin and in the Pale Skin of the
      Catfish.

PMID- 16588677
TI  - Production of Staphylococcus Strains Resistant to Various Concentrations of
      Penicillin.

PMID- 16588678
TI  - The Law of Mass Action in Epidemiology.

PMID- 16588679
TI  - A Letter from Lord Rayleigh to J. Willard Gibbs and His Reply.

PMID- 16588680
TI  - Studies on Geodesics in Vibrations of Elastic Beams.

PMID- 16588681
TI  - An Extension of Lie's Theorem on Isothermal Families.

PMID- 16588682
TI  - New Types of Relations in Finite Field Theory.

PMID- 16588683
TI  - Fermat's Quotient and Related Arithmetic Functions.

PMID- 16588684
TI  - Non-Linear Integral Equations of the Hammerstein Type.

PMID- 16588685
TI  - Inadequacies in Present Knowledge of the Relation Between Photosynthesis and the
      O Content of Atmospheric Oxygen.

PMID- 16588686
TI  - Concerning Tangents to Continua in the Plane.

PMID- 16588687
TI  - Torus Homotopy Groups.

PMID- 16588688
TI  - Experiments on Sexual Isolation in Drosophila: IV. Modification of the Degree of
      Isolation Between Drosophila Pseudoobscura and Drosophila Persimilis and Sexual
      Preferences in Drosophila Prosoltans.

PMID- 16588689
TI  - Dominance Modification and Physiological Effects of Genes.

PMID- 16588690
TI  - Relative Sensitivity of Chromosomes to Neutrons and X-Rays: III. Comparison of
      Carcinoma and Lymphosarcoma in the Rat.

PMID- 16588691
TI  - X-Ray Induced Mutant Strains of Escherichia Coli.

PMID- 16588692
TI  - Carbon Dioxide Utilization in the Synthesis of Acetic Acid by Clostridium
      Thermoaceticum.

PMID- 16588693
TI  - The Crystalline Phases of Soap.

PMID- 16588694
TI  - Willard Gibbs on Soaring Flight.

PMID- 16588695
TI  - Effects of Exposure to Ultra-Violet Light on Visual Thresholds.

PMID- 16588696
TI  - On Plateau's Problem with Free Boundaries.

PMID- 16588697
TI  - The Laplace Equation in Space.

PMID- 16588698
TI  - Algebraic Curves, Symmetries and Satellites.

PMID- 16588699
TI  - Differential Equations in Frechet Differentials Occurring in Integral Equations.

PMID- 16588700
TI  - On the Projective Theory of Two Dimensional Riemann Spaces.

PMID- 16588701
TI  - On Convergence in Length.

PMID- 16588702
TI  - Structure of the Salivary Gland Chromosomes of Diptera.

PMID- 16588703
TI  - The Spread of an Epidemic.

PMID- 16588704
TI  - A Topology for the Set of Primitive Ideals in an Arbitrary Ring.

PMID- 16588705
TI  - Converse of Ptolemy's Theorem on Stereographic Projection.

PMID- 16588706
TI  - The Synthesis of Butyric and Caproic Acids from Ethanol and Acetic Acid by
      Clostridium Kluyveri.

PMID- 16588707
TI  - The Differential Equation of the Distribution of Gene Frequencies.

PMID- 16588708
TI  - Effect of Smoking on Taste Thresholds for Phenyl-Thio-Carbamide (PTC).

PMID- 16588709
TI  - Respiratory Enzymes in Paramecium: 1. Cytochrome Oxidase.

PMID- 16588710
TI  - Offspring from Unborn Mothers.

PMID- 16588711
TI  - Induction of Conjugation in Paramecium Bursaria Among Animals of One Mating Type
      by Fluid from Another Mating Type.

PMID- 16588713
TI  - Generalized Arc-Sets.

PMID- 16588712
TI  - Markoff Chains with Reverse Transitions.

PMID- 16588714
TI  - Two Mean Theorems in Hilbert Space.

PMID- 16588715
TI  - On Classes of Diophantine Equations of Higher Degrees Which Have No Solutions.

PMID- 16588716
TI  - The Transformation of Dynamical Systems of Two Degrees of Freedom.

PMID- 16588717
TI  - The Coefficients of Schlicht Functions: III.

PMID- 16588718
TI  - Growth Correlates of Electromotive Forces in Maize Seeds.

PMID- 16588719
TI  - Intersexes Dependent on a Maternal Effect in Hybrids Between Drosophila Repleta
      and D. Neorepleta.

PMID- 16588720
TI  - The Mechanism of Position Effect-Experiments on the Phenotypic Expression of
      Position Effects in Relation to Changes in Pairing of Neighboring Chromosome
      Regions.

PMID- 16588721
TI  - The Distortion of Angles in General Cartography.

PMID- 16588722
TI  - A Generalization of the Wiener-Hopf Integral Equation.

PMID- 16588723
TI  - Strain Specificity and Production of Antibiotic Substances: VII. Production of
      Actinomycin by Different Actinomycetes.

PMID- 16588724
TI  - Growth Requirements of Virus-Resistant Mutants of Escherichia Coli Strain "B".

PMID- 16588725
TI  - Experiments on Sexual Isolation in Drosophila: VII. The Nature of the Isolating
      Mechanisms Between Drosophila Pseudoobscura and Drosophila Persimilis.

PMID- 16588726
TI  - Two Types of Heterochromatin in Drosophila Nebulosa.

PMID- 16588728
TI  - Prime Number of Operators in Sets of Conjugates.

PMID- 16588727
TI  - Genes Which Divide Species or Produce Hybrid Vigor.

PMID- 16588729
TI  - Comparison of Union-Preserving and Contact Transformations.

PMID- 16588730
TI  - An Ergodic Theorem.

PMID- 16588732
TI  - Rational Functions of a Complex Variable and Related Potential Curves.

PMID- 16588731
TI  - Determination of the Second Homology and Cohomology Groups of a Space by Means of
      Homotopy Invariants.

PMID- 16588733
TI  - Integral and Rational Numbers in the Nuclear Domain and Their Significance.

PMID- 16588734
TI  - On Behrbohm and Pinl's Linearization of the Equation of Two-Dimensional Steady
      Polytropic Flow of a Compressible Fluid.

PMID- 16588735
TI  - Kynurenine as an Intermediate in the Formation of Nicotinic Acid from Tryptophane
      by Neurospora.

PMID- 16588736
TI  - On the Evolution of the Genus Nicotiana.

PMID- 16588737
TI  - Antibiotic Substances from Basidiomycetes: I. Pleurotus griseus.

PMID- 16588738
TI  - Antibiotics from Basidiomycetes: II. Polyporus biformis.

PMID- 16588739
TI  - The Pole Cells of Diptera, Their Fate and Significance.

PMID- 16588740
TI  - A General Class of Problems in Conformal Mapping.

PMID- 16588741
TI  - Continuous Particles.

PMID- 16588742
TI  - Radio-Wave Propagation and Electromagnetic Surface Waves.

PMID- 16588743
TI  - Forces Between Polyatomic Molecules.

PMID- 16588744
TI  - Urethane (Ethyl Carbamate) Therapy in Spontaneous Leukemias in Mice.

PMID- 16588745
TI  - Influence of Humidity on the Survival of Different Chromosomal Types in
      Drosophila Pseudoobscura.

PMID- 16588746
TI  - Perturbations of Discontinuous Solutions of Non-Linear Systems of Differential
      Equations.

PMID- 16588747
TI  - A Minimum Problem About the Motion of a Solid Through a Fluid.

PMID- 16588748
TI  - Reactivation of Irradiated Bacteriophage by Transfer of Self-Reproducing Units.

PMID- 16588749
TI  - Nutritional Life History as Influenced by Dietary Enrichments: I.

PMID- 16588750
TI  - Further Studies of the Influence of Nutrition Upon the Chemical Composition of
      the Body.

PMID- 16588752
TI  - Multiply Valued Harmonic Functions.

PMID- 16588751
TI  - Cytological Phenomena and Sex in Hypomyces Solani F. Cucurbitae.

PMID- 16588753
TI  - On Complexes Over a Ring and Restricted Cohomology Groups.

PMID- 16588754
TI  - The Relationship of Growth Hormones and Fruit Development.

PMID- 16588755
TI  - Nutritional Life History as Influenced by Dietary Enrichments: II. Body Weight
      and Body Calcium in Cases of Protein-Accelerated Growth.

PMID- 16588756
TI  - Depletion Mutation in Saccharomyces.

PMID- 16588757
TI  - Wind-Driven Currents in a Baroclinic Ocean; with Application to the Equatorial
      Currents of the Eastern Pacific.

PMID- 16588758
TI  - The Problems of Congruent Numbers and Concordant Forms.

PMID- 16588759
TI  - On a Theorem of von Neumann.

PMID- 16588760
TI  - Note on Continuous Representations of Lie Groups.

PMID- 16588761
TI  - On Lacunary Trigonometric Series.

PMID- 16588762
TI  - Transformation Theory of Physical Curves.

PMID- 16588763
TI  - The Energy Source for Bioluminescence in an Isolated System.

PMID- 16588764
TI  - Studies on the Biochemistry of Tetrahymena: X. Quantitative Response to Essential
      Amino Acids.

PMID- 16588765
TI  - Effect of Increasing Food Protein Upon the Calcium Content of the Body.

PMID- 16588766
TI  - The Effects of Isolates on the Frequency of a Rare Human Gene.

PMID- 16588767
TI  - The Nature of Gene Action as Shown by Cell-Limited and Cell-Diffusible Gene
      Products.

PMID- 16588768
TI  - The Influence of X-Rays and Near Infra-Red Rays on Recessive Lethals in
      Drosophila Melanogaster.

PMID- 16588769
TI  - On Infinite Complexes with Automorphisms.

PMID- 16588770
TI  - An Oscillation Theorem for Continuous Spectra.

PMID- 16588771
TI  - On the Composition of Quadratic Forms.

PMID- 16588772
TI  - On the Problem of Similar Regions.

PMID- 16588773
TI  - A Proof of Lower Semicontinuity.

PMID- 16588775
TI  - A Simple Second Order Differential Equation with Singular Motions.

PMID- 16588774
TI  - Hydroxyanthranilic Acid as a Precursor of Nicotinic Acid in Neurospora.

PMID- 16588776
TI  - The Number of Zeros of a Polynomial in a Circle.

PMID- 16588777
TI  - Infinite Dimensional Differential Metrics with Constant Curvature.

PMID- 16588778
TI  - The Identification of a Natural Precursor of Nicotinic Acid.

PMID- 16588779
TI  - On Line Congruences.

PMID- 16588780
TI  - Some Remarks on the Weights of Unknowns as Determined by the Method of
      Differential Corrections.

PMID- 16588781
TI  - Galactic and Extragalactic Studies: XVIII. The Pulse Index for Eighty-Nine
      Variable Stars in the Magellanic Clouds.

PMID- 16588782
TI  - The p-Aminobenzoic Acid Requirement of the "Sulfonamide-Requiring" Mutant Strain
      of Neurospora.

PMID- 16588783
TI  - Directed Fertilization in Maize.

PMID- 16588784
TI  - Abstract Ergodic Theorems.

PMID- 16588786
TI  - The Completeness of the Irreducible Unitary Representations of a Locally Compact
      Group.

PMID- 16588785
TI  - Closed Surfaces Without Conjugate Points.

PMID- 16588787
TI  - On Lacunary Trigonometric Series, II.

PMID- 16588788
TI  - Applications of Cyclotomy to the Theory of Non-Homogeneous Equations in a Finite
      Field.

PMID- 16588789
TI  - A Special Class of Solutions of the Equations of the Gravitational Field Arising
      from Certain Gauge-Invariant Action Principles.

PMID- 16588790
TI  - Physical Families of Curves in Space.

PMID- 16588791
TI  - A Physiological Basis for Some Suppressor Mutations and Possibly for One Gene
      Heterosis.

PMID- 16588792
TI  - The Protein of the Salivary Gland Secretion in Drosophila.

PMID- 16588793
TI  - Linkage Studies of the Rat: IX. Cataract.

PMID- 16588794
TI  - The Suppression of Crossing Over in Inversion Heterozygotes of Drosophila
      Pseudoobscura.

PMID- 16588795
TI  - The Role of Mutation and of Selection in the Frequency of Mutants Among
      Microorganisms Grown on Irradiated Substrate.

PMID- 16588796
TI  - On the Average Value of Arithmetic Functions.

PMID- 16588797
TI  - An Inversion and Representation Theory for Convolution Transforms with Totally
      Positive Kernels.

PMID- 16588798
TI  - The Laplace Transform for Locally Compact Abelian Groups.

PMID- 16588799
TI  - On the Asymptotic Distribution of the Sum of a Random Number of Random Variables.

PMID- 16588800
TI  - On Variation-Diminishing Integral Operators of the Convolution Type.

PMID- 16588801
TI  - Physical Curves in Generalized Fields of Force.

PMID- 16588802
TI  - The Effect of Irradiation on Recombination in Escherichia Coli.

PMID- 16588803
TI  - Strain Specificity and Production of Antibiotic Sub-stances: VIII. Production of
      a Grisein-Like Antibiotic by a Strain of Streptomyces Griseus.

PMID- 16588804
TI  - The Gas Turbine and Its Significance as a Prime Mover.

PMID- 16588805
TI  - New Facts on Sex Determination in Drosophila Melanogaster.

PMID- 16588807
TI  - On the Existence of Solutions of Certain Equations in a Finite Field.

PMID- 16588806
TI  - Pigments of Yellow-Eyed Races of the Black-Eyed Susan (Rudbeckia Hirta).

PMID- 16588808
TI  - Groups, Categories and Duality.

PMID- 16588809
TI  - Methods of Symmetry and Critical Points of Harmonic Functions.

PMID- 16588810
TI  - Tuberculosis in Germany.

PMID- 16588811
TI  - Some Relations Between the F's and F's of X-Ray Diffraction.

PMID- 16588812
TI  - Stability of the Laminar Flow Through a Straight Pipe of Circular Cross-Section
      to Infinitesimal Disturbances Which are Symmetrical about the Axis of the Pipe.

PMID- 16588813
TI  - The Mechanism of Flow for Solid Metals.

PMID- 16588814
TI  - Evidence for Aging as a Consequence of Growth Cessation.

PMID- 16588815
TI  - Radial Oscillations of the Limiting Models of Polytropic Gas Spheres.

PMID- 16588816
TI  - Effects of Different Protein and Riboflavin Contents of Diet upon the Chemical
      Composition of the Body.

PMID- 16588817
TI  - On the Frequency and Transmitted Chromosome Alterations and Gene Mutations
      Induced by Atomic Bomb Radiations in Maize.

PMID- 16588818
TI  - The Relation Between Nicotinic Acid and Carbohydrates in a Series of Maize
      Endosperm Genotypes.

PMID- 16588819
TI  - A Gene-Controlled Reaction in Neurospora Involving the Synthesis of Pantothenic
      Acid.

PMID- 16588820
TI  - Multiplicative Systems: I.

PMID- 16588821
TI  - On the Zeros of the Derivative of an Entire Function of Finite Genre.

PMID- 16588822
TI  - Twenty Exact Factorials Between 304! and 401!

PMID- 16588823
TI  - The Determination of Hereditary Antigenic Differences in Genically Identical
      Paramecium Cells.

PMID- 16588824
TI  - The Process of Transformation of Antigenic Type in Paramecium Aurelia, Variety 4.

PMID- 16588825
TI  - Enzymatic Fixation of Carbon Dioxide in alpha-Ketoglutaric Acid.

PMID- 16588826
TI  - Antibiotic Substances from Basidiomycetes: III. Coprinus Similis and Lentinus
      Degener.

PMID- 16588827
TI  - The Bearing of the Living Metasequoia on Problems of Tertiary Paleo-Botany.

PMID- 16588829
TI  - On the Stability and Instability of Shock Waves.

PMID- 16588828
TI  - Influence of Amino Acids on Growth of Datura Embryos in Culture.

PMID- 16588830
TI  - Progress in the Statistical Theory of Turbulence.

PMID- 16588831
TI  - Note on the Law of Decay of Isotropic Turbulence.

PMID- 16588832
TI  - The Cytological Mechanism of the Triploidy-Inducing Effect of Heat on Eggs of the
      Newt, Triturus Viridescens.

PMID- 16588833
TI  - On the Relationships Between the Frequency Functions of Stellar Velocities.

PMID- 16588834
TI  - Amino Acid Constituents of Tissues and Isolated Chromasomes of Drosophila.

PMID- 16588835
TI  - Studies on the Biochemistry of Tetrahymena: XIV. The Activity of Natural Purines
      and Pyrimidines.

PMID- 16588836
TI  - On Leaf Arrangement in Metasequoia Glyptostroboides.

PMID- 16588837
TI  - An Ascent of Koroyanitu.

PMID- 16588838
TI  - Nutritional Life History as Influenced by Dietary Enrichments: III. Full-Life
      Data of 1946-1948 Experiments.

PMID- 16588839
TI  - On the Proteins of aa and aa Ephestia.

PMID- 16588840
TI  - The Rayleigh-Ritz and the Weinstein Methods for Approximation of Eigenvalues: II.
      Differential Operators.

PMID- 16588841
TI  - On the Theory of Age-Dependent Stochastic Branching Processes.

PMID- 16588842
TI  - Conformal Mapping and Convergence of a Power Series.

PMID- 16588843
TI  - Essential Multiplicity and Lebesgue Area.

PMID- 16588844
TI  - Some New Results on Partitions.

PMID- 16588845
TI  - The Isolation of Biochemically Deficient Mutants of Bacteria by Means of
      Penicillin.

PMID- 16588846
TI  - Riboflavin-Sensitized Photooxidation of Indoleacetic Acid and Related Compounds.

PMID- 16588847
TI  - Aggregation Phenomena in Egg Albumin Solutions as Determined by Light Scattering
      Measurements.

PMID- 16588849
TI  - A Theorem on Convex Bodies of the Brunn-Minkowski Type.

PMID- 16588848
TI  - Unusual Gene-Controlled Combinations of Carbohydrate Fermentations in Yeast
      Hybrids.

PMID- 16588850
TI  - The n-Ality Theory of Rings.

PMID- 16588851
TI  - On A Theorem of Dieudonne.

PMID- 16588852
TI  - Osculating Conics of the Integral Curves of Third Order Differential Equations of
      the Type (G).

PMID- 16588853
TI  - Remark Concerning Integration.

PMID- 16588854
TI  - Notes on Integration: IV.

PMID- 16588855
TI  - On the Degree of Convergence of Harmonic Polynomials to Harmonic Functions.

PMID- 16588856
TI  - A Simple Analytical Proof of a Fundamental Property of Birational
      Transformations.

PMID- 16588857
TI  - The Nucleoprotein Content of Whole Nuclei.

PMID- 16588858
TI  - Pharmacological Modification of Resistance to Radiation-A Preliminary-Report.

PMID- 16588859
TI  - Physical Systems of Curves in Space.

PMID- 16588860
TI  - Conjugation Between Double Monsters and Single Animals in Paramecium Bursaria.

PMID- 16588861
TI  - The Nature of the Specificity of Methyl Green for Chromatin.

PMID- 16588862
TI  - Effect of Visible Light on the Recovery of Streptomyces Griseus Conidia from
      Ultra-violet Irradiation Injury.

PMID- 16588863
TI  - The Mode of Action of the Metal-Peptidases.

PMID- 16588865
TI  - On Difference Sets.

PMID- 16588864
TI  - Further Experiments with Vitamin A in Relation to Aging and to Length of Life.

PMID- 16588866
TI  - Characters over Certain Types of Rings with Applications to the Theory of
      Equations in a Finite Field.

PMID- 16588867
TI  - Bayes Solutions of Sequential Decision Problems.

PMID- 16588868
TI  - National Academy of Sciences (Distribution and Ages of Membership).

PMID- 16588869
TI  - The Miocene Occurrence of Sequoia and Related Conifers in the John Day Basin.

PMID- 16588870
TI  - A Note on Centromere Organization.

PMID- 16588871
TI  - Primary Ideals in Group Algebras.

PMID- 16588872
TI  - Integral Representations of Bilinear Functionals.

PMID- 16588873
TI  - The Coefficients of Schlicht Functions: IV.

PMID- 16588874
TI  - On Zermelo's and Von Neumann's Axioms for Set Theory.

PMID- 16588875
TI  - The Culture of Paramecium Aurelia in the Absence of Other Living Organisms.

PMID- 16588876
TI  - Some Problems of the Evolution of Stars.

PMID- 16588877
TI  - The Action of Alleic Forms of the Gene A in Maize: II. The Relation of Crossing
      over to Mutation of A.

PMID- 16588878
TI  - Aberrant Heterozygotes in Escherichia Coli.

PMID- 16588879
TI  - The In Vitro Synthesis of Pantothenic Acid by Pantothenicless and Wild Type
      Neurospora.

PMID- 16588880
TI  - Bounds for the Solutions of a Second-Order Linear Differential Equation.

PMID- 16588881
TI  - Principal Quadratic Functionals and Self-Adjoint Second-Order Differential
      Equations.

PMID- 16588883
TI  - Crystallographic Symmetry in Reciprocal Space.

PMID- 16588882
TI  - The Mechanism of Proteinuria.

PMID- 16588884
TI  - Physical Curves in Space of n Dimensions.

PMID- 16588885
TI  - On Bending of Curved Thin-Walled Tubes.

PMID- 16588886
TI  - Note on the Theory of Lifting Surfaces.

PMID- 16588887
TI  - Responses of the Proximal Retinal Pigment of the Isolated Crustacean Eyestalk to
      Light and to Darkness.

PMID- 16588888
TI  - The Surface Gel Layer of Fundulus Eggs in Relation to Epiboly.

PMID- 16588889
TI  - Values as a Subject of Natural Science Inquiry.

PMID- 16588890
TI  - Individual Metabolic Patterns, Alcoholism, Genetotrophic Diseases.

PMID- 16588891
TI  - Inhibition of Plant Growth by Protoanemonin and Coumarin, and Its Prevention by
      Bal.

PMID- 16588892
TI  - Developmental Analysis of Genetic Differences in Pigmentation in the Axolotl.

PMID- 16588893
TI  - Inheritance of Carotenoid Differences in Lycopersicon Esculentum Strains.

PMID- 16588894
TI  - Infrared Absorption in Field Studies of Olfaction in Honeybees.

PMID- 16588895
TI  - The Beaded Minute combination and sex-determination in Drosophila.

PMID- 16588896
TI  - The Intersexual Males of the Beaded Minute Combination in Drosophila
      Melanogaster.

PMID- 16588897
TI  - A Theory of Trace-Admissible Algebras.

PMID- 16588898
TI  - The Homotopy Groups of a Triad.

PMID- 16588899
TI  - On the "Central" Probability Problem.

PMID- 16588900
TI  - On Congruences which relate the Fermat and Wilson Quotients to the Bernoulli
      Numbers.

PMID- 16588901
TI  - Second Order Differential Equations of Rank 2 in Physics.

PMID- 16588902
TI  - Antibiotic Substances from Basidiomycetes: IV. Marasmius Conigenus.

PMID- 16588903
TI  - Chromosome Segregation in Maize Translocations in Relation to Crossing Over in
      Interstitial Segments.

PMID- 16588904
TI  - Early Tertiary Ecotones in Western North America.

PMID- 16588905
TI  - The Dissociation Energy of Carbon Monoxide and the Heat of Sublimation of
      Graphite.

PMID- 16588906
TI  - Aggregation Phenomena in Polyvinyl Alcohol-Acetate Solutions.

PMID- 16588907
TI  - Diffusion Equation and Stochastic Processes.

PMID- 16588908
TI  - On Epstein's Zeta Function (I).

PMID- 16588909
TI  - On a New Method in Elementary Number Theory Which Leads to An Elementary Proof of
      the Prime Number Theorem.

PMID- 16588910
TI  - On the Structure of Locally Compact Groups.

PMID- 16588911
TI  - On the Automorphisms of a Sfield.

PMID- 16588912
TI  - Lie Rings in Path Space.

PMID- 16588913
TI  - The Frechet Variation and the Convergence of Multiple Fourier Series.

PMID- 16588914
TI  - On the Zeros of Successive Derivatives of Entire Functions.

PMID- 16588915
TI  - Homotopy Groups of Certain Algebraic Systems.

PMID- 16588916
TI  - Inequalities between the Two Kinds of Eigenvalues of a Linear Transformation.

PMID- 16588917
TI  - Separation of the Variables in the One-Particle Schroedinger Equation in 3-Space.

PMID- 16588918
TI  - Physical Families in Conservative Fields of Force.

PMID- 16588919
TI  - A Method of Effecting Zygospore Germination in Certain Chlorophyceae.

PMID- 16588920
TI  - Studies on the Biochemical Genetics of Yeast.

PMID- 16588921
TI  - Variation in the Amount of Desoxyribose Nucleic Acid in Different Tissues of
      Tradescantia.

PMID- 16588922
TI  - Chromosomes of a Fox Hybrid (Alopex-Vulpes).

PMID- 16588923
TI  - Continued Fractions, Algebraic Functions and the Pade Table.

PMID- 16588924
TI  - On the Number of Solutions of Some Trinomial Equations in a Finite Field.

PMID- 16588926
TI  - Superconductivity and the Bohr Magneton.

PMID- 16588925
TI  - On the Nature of the Solutions of Certain Equations in a Finite Field.

PMID- 16588927
TI  - Separation of the Variables of the Two-Particle Wave Equation.

PMID- 16588928
TI  - On the Stability of the S(8) Molbcule and the Structure of Fibrous Sulfur.

PMID- 16588929
TI  - Evidence for a Tryptophane Cycle in Neurospora.

PMID- 16588930
TI  - The Correlation in Shape and Size Between Epidermal and Subepidermal Cells.

PMID- 16588931
TI  - The Effect of Nitrogen Mustard Pretreatment on the Ultra-Violet-Induced
      Morphological and Biochemical Mutation Rate.

PMID- 16588932
TI  - The Principles of Time Series Analyses Applied to Ocean Wave Data.

PMID- 16588933
TI  - The Class Number of the Cyclotomic Field.

PMID- 16588934
TI  - Some Properties of a Sfield.

PMID- 16588935
TI  - Imprimitivity for Representations of Locally Compact Groups I.

PMID- 16588936
TI  - Linkage studies of the Rat: X.

PMID- 16588937
TI  - A Generalization of the Schwarz-Christoffel Transformation.

PMID- 16588938
TI  - On Some Generalizations of the Cauchy-Frullani Integral.

PMID- 16588939
TI  - Antibiotic Substances from Basidiomycetes: V. Poria Corticola, Poria Tenuis and
      an Unidentified Basidiomycete.

PMID- 16588940
TI  - Note on a Relation in Dirac's Theory of the Electron.

PMID- 16588941
TI  - The Influence of Size of Test-Field Surround on Visual Intensity Discrimination.

PMID- 16588943
TI  - On a Theorem of Weyl Concerning Eigenvalues of Linear Transformations: II.

PMID- 16588942
TI  - Homogeneous Contact Transformations.

PMID- 16588944
TI  - A Commutativity Theorem for Normal Operators.

PMID- 16588945
TI  - On the 3-Type of a Complex.

PMID- 16588946
TI  - Equilibrium Points in N-Person Games.

PMID- 16588947
TI  - Remark on Weyl's Note "Inequalities Between the Two Kinds of Eigenvalues of a
      Linear Transformation".

PMID- 16588948
TI  - Singular Points of Functions Defined by C-Fractions.

PMID- 16588949
TI  - The Secondary Boundary Operator.

PMID- 16588950
TI  - Theorems on Quadratic Partitions.

PMID- 16588951
TI  - Factors Determining Solubility among Non-Electrolytes.

PMID- 16588952
TI  - Antibiotic Substances from Basidiomycetes: VI. Agrocybe Dura.

PMID- 16588954
TI  - Distribution of Pressure on Curved Profiles in Supersonic Gas Flow with Variable
      Entropy.

PMID- 16588953
TI  - Quantitative Effects of Protein Enrichment of Diet upon Growth and Early Adult
      Life.

PMID- 16588955
TI  - The Selective Advantage of an Adenineless Double Mutant Over One of the Single
      Mutants Involved.

PMID- 16588956
TI  - Higher Properties of Physical Systems of Curves.

PMID- 16588957
TI  - Theoretical Relationships Among Some Measures of Conditioning.

PMID- 16588958
TI  - Partial Differential Equations and Generalized Analytic Functions.

PMID- 16588959
TI  - The Exceptional Simple Lie Algebras F(4) and E(6).

PMID- 16588960
TI  - A Topologized Fundamental Group.

PMID- 16588961
TI  - On a Generalization of a Jacobi Exponential Sum Associated with Cyclotomy.

PMID- 16588963
TI  - A Note on the Mean Square Velocity in Stellar Statistics.

PMID- 16588962
TI  - On Distortion at the Boundary of a Conformal Map.

PMID- 16588964
TI  - Radial Oscillations of Compressible Gas Spheres.

PMID- 16588965
TI  - The Synthesis of Rhodopsin from Retinene(1).

PMID- 16588966
TI  - The Synthesis of Rhodopsin from Vitamin A(1).

PMID- 16588967
TI  - Galactic and Extragalactic Studies: XX. On the Distribution of 78,000 of the
      Brighter Northern Galaxies.

PMID- 16588968
TI  - Evidence for the Participation of Kynurenine as a Normal Intermediate in the
      Biosynthesis of Niacin in Neurospora.

PMID- 16588969
TI  - The Effect of Oxygen Concentration on the Rate of X-Ray Induced Mutations in
      Drosophila.

PMID- 16588970
TI  - Some Remarks on the Infinite De Sitter Space.

PMID- 16588972
TI  - Absolute and Unconditional Convergence in Normed Linear Spaces.

PMID- 16588971
TI  - The Effect of Seminal Plasma on Fertilized Rabbit Ova.

PMID- 16588973
TI  - The Region of Values of the Derivative of a Schlicht Function.

PMID- 16588974
TI  - A Generalization of Poisson's Distribution for Markoff Chains.

PMID- 16588976
TI  - On Membranes and Plates.

PMID- 16588975
TI  - Almost Periodic Invariant Vector Sets in a Metric Vector Space.

PMID- 16588977
TI  - Sphere-Geometrical Unitary Field Theory.

PMID- 16588978
TI  - Cohomology Theory of Abelian Groups and Homotopy Theory II.

PMID- 16588979
TI  - Arcs in Locally Compact Groups.

PMID- 16588980
TI  - Pseudo-Conformal Geometry of Polygenic Functions of Several Complex Variables.

PMID- 16588981
TI  - The Element of Volume of the Rotation Group.

PMID- 16588982
TI  - Schwarz' Inequality and Lorentz Spaces.

PMID- 16588984
TI  - On the Origin of the Solar System.

PMID- 16588983
TI  - On the Derivation of Space Densities in Globular Clusters.

PMID- 16588985
TI  - Proxima Centauri as a Flare Star.

PMID- 16588986
TI  - The Theory of Micro-Meteorites: Part II. In Heterothermal Atmospheres.

PMID- 16588987
TI  - Partial Differential Equations and Generalized Analytic Functions: Second Note.

PMID- 16588989
TI  - On the Analysis of Representations of the Linear Group.

PMID- 16588988
TI  - The Harmonic Operator for Exterior Differential Forms.

PMID- 16588990
TI  - The Characters of the Symmetric Group.

PMID- 16588992
TI  - Many-Figure Approximations to radical2, and Distribution of Digits in radical2
      and 1/ radical2.

PMID- 16588991
TI  - Vector Fields on the n-Sphere.

PMID- 16588993
TI  - Magellanic Clouds: I. Transparency.

PMID- 16588994
TI  - Magellanic Clouds: II. Supergiant Red Variable Stars in the Small Cloud.

PMID- 16588996
TI  - The Jacobson Radical of a Semiring.

PMID- 16588995
TI  - A Condition For a Real Lattice to Define a Zeta Function.

PMID- 16588997
TI  - Representations of Semisimple Lie Groups on a Banach Space.

PMID- 16588998
TI  - A Non-Reflexive Banach Space Isometric With Its Second Conjugate Space.

PMID- 16588999
TI  - Probabilistic Theories of Relations.

PMID- 16589000
TI  - Harmonic Forms and Heat Conduction: I: Closed Riemannian Manifolds.

PMID- 16589001
TI  - Galactic and Extragalactic Studies: XXI. Distribution of 95,000 Galaxies in the
      North Galactic Cap.

PMID- 16589002
TI  - Curve of Growth Polarization.

PMID- 16589003
TI  - Concerning Non-Continuable, Transcendentally Transcendental Power Series.

PMID- 16589004
TI  - Simple Waves in the Complete General Problem of Plasticity Theory.

PMID- 16589005
TI  - Continuous Games.

PMID- 16589006
TI  - Theory of Turns and Slides Upon a Surface.

PMID- 16589008
TI  - Numerical Results for Pressure-Velocity Correlations in Homogeneous Isotropic
      Turbulence.

PMID- 16589007
TI  - Probabilistic Geometry.

PMID- 16589009
TI  - On the Generating Functions of Totally Positive Sequences.

PMID- 16589010
TI  - Cohomology Theory of Abelian Groups and Homotopy Theory III.

PMID- 16589011
TI  - Generalized Riemann Spaces.

PMID- 16589012
TI  - Weierstrass Transforms of Positive Functions.

PMID- 16589013
TI  - Simultaneous Use of Molecular Nitrogen and Ammonia by Clostridium Pasteurianum.

PMID- 16589014
TI  - The Virus of Vaccinia in Chick Embryo Membrane.

PMID- 16589015
TI  - Antibiotic Substances From Basidiomycetes: VIII. Pleurotus Multilus (Fr.) Sacc.
      and Pleurotus Passeckerianus Pilat.

PMID- 16589016
TI  - Immunologic Adsorbents: I. Isolation of Antibody by Means of a Cellulose-Protein
      Antigen.

PMID- 16589017
TI  - The Potential of an Infinite Rod-Like Molecule and the Distribution of the
      Counter Ions.

PMID- 16589018
TI  - The Effect of Ultra-Violet Radiation on a Ring Chromosome in Zea Mays.

PMID- 16589020
TI  - On Finite Groups With Two Independent Generators: I.

PMID- 16589019
TI  - Sound Waves in the Atmosphere Generated by a Small Earthquake.

PMID- 16589021
TI  - On the Basis Theorem for Finite Abelian Groups (Third Note).

PMID- 16589022
TI  - Harmonic Tensors on Manifolds with Boundary.

PMID- 16589023
TI  - A Summary of New Results Concerning the Solutions of Equations in Finite Fields.

PMID- 16589024
TI  - Compact Subgroups.

PMID- 16589025
TI  - Differential Invariants and Invariant Partial Differential Equations Under
      Continuous Transformation Groups in Normed Linear Spaces.

PMID- 16589026
TI  - A Factorial Study of the Supreme Court.

PMID- 16589027
TI  - A Third Abnormal Hemoglobin Associated with Hereditary Hemolytic Anemia.

PMID- 16589028
TI  - Spontaneous and Ultra-Violet-Induced Mutations to Phage Resistance in Escherichia
      Coli.

PMID- 16589029
TI  - Experiments on Sexual Isolation in Drosophila: X. Reproductive Isolation Between
      Drosophila Pseudoobscura and Drosophila Persimilis Under Natural and Under
      Laboratory Conditions.

PMID- 16589030
TI  - The Induction of Activated, Stable States in the Chromosomes of Tradescantia by
      Infra-red and X-Rays.

PMID- 16589031
TI  - The Interaction of a Minute Mutation with a Sex-linked Lethal of Drosophila
      Melanogaster.

PMID- 16589032
TI  - Theta Relations with Spherical Harmonics.

PMID- 16589033
TI  - On Finite Groups with Two Independent Generators: IV. Conjugate Substitutions.

PMID- 16589035
TI  - Alternative Division Rings of Characteristic 2.

PMID- 16589034
TI  - Plancherel Formula for Complex Semisimple Lie Groups.

PMID- 16589036
TI  - Note on Approximation by Bounded Analytic Functions.

PMID- 16589037
TI  - On a Theorem of Hardy, Littlewood, Polya, and Blackwell.

PMID- 16589039
TI  - Electron-Neutron Interaction.

PMID- 16589038
TI  - Radiation Capacity.

PMID- 16589040
TI  - Finding the Signs of the F's from the Shifted Patterson Product.

PMID- 16589041
TI  - The Optical Theory of Willard Gibbs.

PMID- 16589042
TI  - Oxidative and Phosphorylative Activity of Plant Mitochondria.

PMID- 16589043
TI  - Hybridization and Embryonic Temperature Adaptation Studies of Rana Temporaria and
      Rana Sylvatica.

PMID- 16589044
TI  - A New Discussion of the Changes in the Earth's Rate of Rotation.

PMID- 16589045
TI  - Gastric Anion Exchange: Its Relation to the Immediate Mechanism of Hydrochloric
      Acid Secretion.

PMID- 16589046
TI  - A Hemochromogen Component of Liver Microsomes.

PMID- 16589047
TI  - Incomplete Genetic Blocks in Biochemical Mutants of Neurospora.

PMID- 16589048
TI  - The Effects of Carbon Monoxide and Oxygen on the Frequency of X-Ray Induced
      Chromosome Aberrations in Tradescantia.

PMID- 16589049
TI  - Studies on a Suppressor of Non-Allelic Acetate-Requiring Mutants of Neurospora.

PMID- 16589050
TI  - Carotenoid Differences in Tomatoes.

PMID- 16589051
TI  - On Certain Diophantine Equations in Rings and Fields.

PMID- 16589052
TI  - A Remark on Cavitational Flow.

PMID- 16589053
TI  - Nuclear Studies on the Myxophyceae, a Preliminary Report.

PMID- 16589054
TI  - Inequalities for Complex Linear Differential Systems of the Second Order.

PMID- 16589055
TI  - A Topological Characterization of the Length of Paths.

PMID- 16589056
TI  - The Element of Volume of the Rotation Group.

PMID- 16589057
TI  - Effect of Bilateral Adrenalectomy on Certain Human Tumors.

PMID- 16589058
TI  - Cauchy's Formula on Kahler Manifolds.

PMID- 16589059
TI  - Spectral Sensitivity of the Cones in the Dark Adapted Human Eye.

PMID- 16589060
TI  - Configurations of Polypeptide Chains with Equivalent Cis Amide Groups.

PMID- 16589061
TI  - The Production of Indole Acetic Acid by Ustilago Zeae, and Its Possible
      Significance in Tumor Formation.

PMID- 16589062
TI  - The Structure of Chlorine Hydrate.

PMID- 16589063
TI  - On the Homomorphism Theorem for Semirings.

PMID- 16589064
TI  - A Note on pi(r)(V).

PMID- 16589065
TI  - Fixed-point and Minimax Theorems in Locally Convex Topological Linear Spaces.

PMID- 16589066
TI  - On a Convenient System of Parameters for the Unitary Group.

PMID- 16589067
TI  - On the Modular Representations of the Symmetric Group (II).

PMID- 16589068
TI  - The Place Principle in Auditory Theory.

PMID- 16589069
TI  - The Isolation and Chemical Properties of the Nucleoli of Starfish Oocytes.

PMID- 16589070
TI  - Potential Theory in Space of n Dimensions (Part I).

PMID- 16589071
TI  - Some Observations on the Error of Bio-Assay.

PMID- 16589072
TI  - Variation in the Amounts of Desoxyribose Nucleic Acid (DNA) in Cells of the Same
      Tissue and its Correlation with Secretory Function.

PMID- 16589073
TI  - Chemical Valence Forces and Binding Energy Calculations.

PMID- 16589074
TI  - Superposition of Configurations: The Helium Atom.

PMID- 16589075
TI  - A Comparative Survey of Approximate Ground State Wave Functions of Helium Atom
      and Hydrogen Molecule.

PMID- 16589076
TI  - The Radiation Sensitivity of Catalase as a Function of Temperature.

PMID- 16589077
TI  - The Physical Inactivation of Invertase.

PMID- 16589078
TI  - Ionizing Particle Evidence for the Molecular Weight of the Pneumococcus
      Transforming Principle.

PMID- 16589079
TI  - Studies on the Hemoglobin of Cooley's Anemia and Cooley's Trait.

PMID- 16589080
TI  - Threonine Inhibition in a Strain of Neurospora.

PMID- 16589081
TI  - Observations on the Behavior of Suppressors in Neurospora.

PMID- 16589082
TI  - The Effects of Gene Change on Tryptophan Desmolase Formation.

PMID- 16589083
TI  - Partial Differential Equations and Analytic Continuations.

PMID- 16589084
TI  - The Dirichlet Problem for Linear Elliptic Equations of Arbitrary Even Order with
      Variable Coefficients.

PMID- 16589085
TI  - Integration of Stiff Equations.

PMID- 16589086
TI  - The Elementary Basic Principles of the Unified Theory of Relativity.

PMID- 16589087
TI  - Homology Relations on Regular Orientable Manifolds.

PMID- 16589088
TI  - Criteria for Linear Equivalence.

PMID- 16589089
TI  - Rapid Effects Upon the Renal Circulation Produced by Nephrotoxic Globulin
      Administration in the Rat.

PMID- 16589090
TI  - Shape and Movement of Mesenchyme Cells as Functions of the Physical Structure of
      the Medium: Contributions to a Quantitative Morphology.

PMID- 16589091
TI  - Magellanic Clouds: III. Differential Absorption Within the Large Cloud.

PMID- 16589092
TI  - Magellanic Clouds: IV. On the Period Frequency Anomalies.

PMID- 16589093
TI  - Breakage of Chromosomes by Oxygen.

PMID- 16589094
TI  - Mutant Isoalleles at the Vermilion Locus in Drosophila Melanogaster.

PMID- 16589095
TI  - The Paracompactness of the Weak Simplicial Complex.

PMID- 16589096
TI  - Some Problems Involving Primitive Roots in a Finite Field.

PMID- 16589097
TI  - On Analytic Surfaces with Two Independent Meromorphic Functions.

PMID- 16589098
TI  - Cohomology Groups of Abelian Groups and Homotopy Theory IV.

PMID- 16589099
TI  - The Apparition Problem for Equianharmonic Divisibility Sequences.

PMID- 16589101
TI  - Plancherel Formula for the 2 x 2 Real Unimodular Group.

PMID- 16589100
TI  - Some Theorems on Piecewise Linear Embedding.

PMID- 16589102
TI  - On Solutions of Maxwell's Equations in an Exterior Region.

PMID- 16589103
TI  - On Cohomology Theories.

PMID- 16589104
TI  - On the Early Chemical History of the Earth and the Origin of Life.

PMID- 16589105
TI  - Some Comments on the London-Brooks Treatment of Diamagnetic Anisotropy.

PMID- 16589106
TI  - pi-Electrons and sigma-Electrons.

PMID- 16589107
TI  - On the Anomalous Transparency of Thick Crystals to X-Rays.

PMID- 16589108
TI  - Antibiotic-Producing Properties of Streptomyces 3560, A Member of the S. Flavus
      Group.

PMID- 16589109
TI  - The Relationship Between Photosynthesis and Nitrogen Fixation.

PMID- 16589110
TI  - Oxidation-Reduction Potentials of the Diphosphopyridine Nucleotide System.

PMID- 16589111
TI  - On the Distribution of Charge in the CO Bond of CO(2).

PMID- 16589112
TI  - A New Theory of Vortex Streets.

PMID- 16589113
TI  - Complex Fiber Bundles.

PMID- 16589114
TI  - The Einstein Connection of the Unified Theory of Relativity.

PMID- 16589115
TI  - Some Remarks on Representations of Connected Groups.

PMID- 16589116
TI  - On the Modular Representations of the Symmetric Group (III).

PMID- 16589117
TI  - Fiber Spaces and the Eilenberg Homology Groups.

PMID- 16589118
TI  - On an Application of Tarski's Theory of Truth.

PMID- 16589119
TI  - On the Existence of Subsonic Flows of a Compressible Fluid.

PMID- 16589120
TI  - Group Invariant Integration and the Fundamental Theorem of Algebra.

PMID- 16589121
TI  - Small Subgroups of Finite-Dimensional groups.

PMID- 16589122
TI  - A Case of "Maternal" Inheritance in Neurospora Crassa.

PMID- 16589123
TI  - On the Law of Conservation of Heavy Particles.

PMID- 16589124
TI  - On the Sodium and Potassium Balance of Isolated Frog Muscles.

PMID- 16589125
TI  - Transplantation of Living Nuclei From Blastula Cells into Enucleated Frogs' Eggs.

PMID- 16589126
TI  - Cytochemical Studies of the Action of Trypsin: I. Digestion of Salivary-Gland
      Chromosomes.

PMID- 16589127
TI  - Experiments on the Effects in Heterozygous Condition of Second Chromosomes from
      Natural Populations of Drosophila Willistoni.

PMID- 16589128
TI  - Selection Against Heterozygotes for Autosomal Lethals in Natural Populations of
      Drosophila Willistoni.

PMID- 16589129
TI  - The Accumulation of alpha-Phenylglycine by Mutants of Neurospora Crassa
      Stimulated by Phenylalanine and Tyrosine.

PMID- 16589130
TI  - The Effect of Oxygen Concentration on X-ray Induced Chromosome Breakage in Maize.

PMID- 16589131
TI  - New White Dwarfs in the Southern Hemisphere: Second List.

PMID- 16589132
TI  - The Spatial Correlation of Electrons in Atoms and Molecules II.

PMID- 16589133
TI  - Growth of Analytic Functions Along a Line.

PMID- 16589134
TI  - Generalized Riemann Spaces: II.

PMID- 16589135
TI  - On the Statistical Theory of Turbulent Diffusion.

PMID- 16589136
TI  - The Number of Solutions of Certain Equations in a Finite Field.

PMID- 16589137
TI  - On Spectral Analysis of Stationary Time Series.

PMID- 16589138
TI  - On the Theorem of Riemann-Roch for Adjoint Systems on Kahlerian Varieties.

PMID- 16589139
TI  - Arithmetic Genera of Algebraic Varieties.

PMID- 16589140
TI  - A Generalization of a Theorem of Hodge.

PMID- 16589141
TI  - Power-Associative Commutative Algebras of Degree Two.

PMID- 16589142
TI  - Some Results on Abelian Groups.

PMID- 16589143
TI  - Nature of Inherited Resistance to Viruses Affecting the Nervous System.

PMID- 16589144
TI  - On Quantum-Mechanical Methods in Valence Theory.

PMID- 16589145
TI  - Antibiotic Substances from Basidiomycetes: IX. Drosophila Subtarata. (Batsch Ex
      Fr.) Quel.

PMID- 16589146
TI  - Arginosuccinic Acid from Chlorella.

PMID- 16589147
TI  - The Mechanism of Polymerization of Fibrinogen.

PMID- 16589148
TI  - Pseudo-Wild Types in Neurospora Crassa.

PMID- 16589149
TI  - The Genotype of the Endosperm and Embryo as it Influences Vivipary in Maize.

PMID- 16589150
TI  - Substrate Stabilization of Enzyme-Forming Capacity During the Segregation of a
      Heterozygote.

PMID- 16589151
TI  - An Algebra of Unbounded Operators.

PMID- 16589152
TI  - Commutative Operator Algebras.

PMID- 16589153
TI  - On the Poincare Polynomial of the full Linear Group.

PMID- 16589154
TI  - On the Poincare Polynomials of the Classical Groups.

PMID- 16589155
TI  - An Inequality with Alternating Signs.

PMID- 16589156
TI  - Poliomyelitis and the Weather.

PMID- 16589157
TI  - Antibiotic Substances from Basidiomycetes: X. Fomes Juniperinus Schrenk.

PMID- 16589158
TI  - Sexuality in the Acrasiales.

PMID- 16589159
TI  - A Reversible Photoreaction Controlling Seed Germination.

PMID- 16589160
TI  - Absolute Rate Theory for Isolated Systems and the Mass Spectra of Polyatomic
      Molecules.

PMID- 16589161
TI  - The Structure of Stable Pentaborane.

PMID- 16589162
TI  - An Induced Maternal Effect on the Stability of the Ring-X-Chromosome of
      Drosophila Melanogaster.

PMID- 16589163
TI  - The Virulence of Biochemical Mutants of Klebsiella Pneumoniae.

PMID- 16589164
TI  - The Role of Oxygen Concentration in Determining the Effectiveness of X-Rays on
      the Action of a Specific Gene in Drosophila Melanogaster.

PMID- 16589165
TI  - A Genetic Analysis of the Adaptive Values of Populations.

PMID- 16589166
TI  - On the Theory of Dynamic Programming.

PMID- 16589167
TI  - The Iteration of the Steenrod Squares in Algebraic Topology.

PMID- 16589169
TI  - On the Spectral Representation of Ordinary Self-Adjoint Differential Operators.

PMID- 16589168
TI  - Local Transformations with Fixed Points on Complex Spaces with Singularities.

PMID- 16589170
TI  - On the Multiplication of Representations of the Linear Group.

PMID- 16589171
TI  - The Dirichlet and Vibration Problems for Linear Elliptic Differential Equations
      of Arbitrary Order.

PMID- 16589172
TI  - Production of Plaques in Monolayer Tissue Cultures by Single Particles of an
      Animal Virus.

PMID- 16589173
TI  - Sign and Symbol in Bee Communications.

PMID- 16589174
TI  - Viscosities of Solutions of Bi-Bolaform Electrolytes.

PMID- 16589175
TI  - Theory of the Chemical Reaction Rate Constant.

PMID- 16589176
TI  - The Effect of Auxin on Growth and Respiration of Artichoke Tissue.

PMID- 16589177
TI  - Analysis of the Biochemical Mechanism of Drug Resistance in Certain Bacterial
      Mutants.

PMID- 16589178
TI  - Production of an Altered Pantothenate-Synthesizing Enzyme by a Temperature
      Sensitive Mutant of Escherichia Coli.

PMID- 16589179
TI  - Transduction of Multiple Nutritional Requirements in Salmonella Typhimurium.

PMID- 16589180
TI  - A Comparison of the Effects of X-Rays and Thermal Neutrons on Dormant Seeds of
      Barley.

PMID- 16589181
TI  - The Effects of Carbon Dioxide on the Frequency of X-Ray Induced Chromosome
      Aberrations in Tradescantia.

PMID- 16589182
TI  - Competition Between Drosophila Melanogaster and Drosophila Simulans: II. The
      Improvement of Competitive Ability Through Selection.

PMID- 16589183
TI  - A Morphological Basis for Higher Niacin in Sugary Maize.

PMID- 16589184
TI  - The Fourier Heat Equation in Riemannian Space.

PMID- 16589185
TI  - The Isolation and Biochemical Characterization of the Mitotic Apparatus of
      Dividing Cells.

PMID- 16589186
TI  - Galactic and Extragalactic Studies: XXII. Extent of the Galaxy in the Anticenter
      Octant.

PMID- 16589187
TI  - Natural and Acquired Resistance of Escherichia coli to Neomycin.

PMID- 16589188
TI  - A New type of Periodic Structure Obtained by Reconstitution of Paramyosin from
      Acid Solutions.

PMID- 16589189
TI  - The Influence of Dipole Moment Fluctuations on the Dielectric Increment of
      Proteins in Solution.

PMID- 16589190
TI  - Forces between Protein Molecules in Solution Arising from Fluctuations in Proton
      Charge and Configuration.

PMID- 16589191
TI  - An Association of Hereditary Eye Defects with White Spotting.

PMID- 16589192
TI  - "Bent-Tail," A Dominant, Sex-Linked Mutation in the Mouse.

PMID- 16589193
TI  - The Insolubility of Sets of Diophantine Equations in the Rational Numbers.

PMID- 16589194
TI  - On the Normal Order of Arithmetic Functions.

PMID- 16589195
TI  - A Social Equilibrium Existence Theorem.

PMID- 16589196
TI  - A Relation between Poles and Zeros of a Simple Meromorphic Differential Form and
      a Calculation of Chern's Characteristic Classes of an Algebraic Variety.

PMID- 16589197
TI  - A Note on Automorphic Varieties.

PMID- 16589198
TI  - Barnard's CSM Test of Significance.

PMID- 16589199
TI  - The Newtonian Potential of a Sphere of Euclidean Space E Embedded in a Euclidean
      Universe E.

PMID- 16589201
TI  - Conformal Relativity.

PMID- 16589200
TI  - The Copper Metabolism of Drosophila.

PMID- 16589202
TI  - Production of Illudin M and of a Fourth Crystalline Compound by Clitocybe
      Illudens.

PMID- 16589203
TI  - The Reaction Controlling Floral Initiation.

PMID- 16589204
TI  - Electron Exchange-Polymers.

PMID- 16589205
TI  - The Thermal Decomposition of Cyclobutane.

PMID- 16589207
TI  - The Beadex Locus in Drosophila Melanogaster: The Genotypic Constitution of Bx.

PMID- 16589206
TI  - An Ultracentrifuge Cell for Producing Boundaries Synthetically by a Layering
      Technique.

PMID- 16589209
TI  - On the Number of Bound States in a Central Field of Force.

PMID- 16589208
TI  - The Pseudoallelism of White and Apricot in Drosophila Melanogaster.

PMID- 16589210
TI  - On the Invariant Theory of the Classical Groups.

PMID- 16589211
TI  - On the Decomposition of Tensors by Contraction.

PMID- 16589212
TI  - The Hypothesis that all Classes are Nameable.

PMID- 16589213
TI  - On Cyclotomy and Extensions of Gaussian Type Quadratic Relations Involving
      Numbers of Solutions of Conditional Equations in Finite Fields.

PMID- 16589214
TI  - Preliminary Report on the Experimental Induction of Metastases from a
      Heterologous Cancer Graft in Mice.

PMID- 16589215
TI  - An Invariant Force Function in Muscle Activity.

PMID- 16589216
TI  - A Theory Concerning the Mechanism of Fatty Acid Oxidation and of Carbon Dioxide
      Fixation.

PMID- 16589218
TI  - Conductance of Solutions of Salts in Bromine.

PMID- 16589217
TI  - Auxin-Induced Growth Inhibition a Natural Consequence of Two-Point Attachment.

PMID- 16589219
TI  - Velocity Ultracentrifugation of Heteropoly Acids.

PMID- 16589220
TI  - On Variations of the Geomagnetic Field, Fluid Motions, and the Rate of the
      Earth's Rotation.

PMID- 16589221
TI  - On the Quotient Variety of an Abelian Variety.

PMID- 16589222
TI  - A Theorem About Characteristics of Differential Equations on Closed Manifolds.

PMID- 16589223
TI  - On the Completeness of Quantification Theory.

PMID- 16589224
TI  - The Schrodinger Final Affine Field Laws.

PMID- 16589225
TI  - Degree of Approximation on a Jordan Curve.

PMID- 16589226
TI  - Studies on the Metabolism of Plant Neoplasms: V. Auxin as a Promoting Agent in
      the Transformation of Normal to Crown-Gall Tumor Cells.

PMID- 16589227
TI  - The Rare Occurrence of Mitosis Without Spindle Apparatus ("Colchicine Mitosis")
      Producing Endopolyploidy in Embryos of the Axolotl.

PMID- 16589228
TI  - Magellanic Clouds: V. Fifty Eclipsing Stars.

PMID- 16589229
TI  - Phenomena in the Liquid-Liquid Critical Region.

PMID- 16589230
TI  - Chromatographic Separation and Identification of Some Peptides in Partial
      Hydrolysates of Gelatin.

PMID- 16589231
TI  - Viability of Hybrids Between Local Populations of Drosophila Pseudoobscura.

PMID- 16589232
TI  - On Complexes with Operators.

PMID- 16589233
TI  - Minimax Theorems.

PMID- 16589234
TI  - On the Poincare Polynomials of the Classical Groups-Addendum.

PMID- 16589235
TI  - On Eigenfunction Expansions.

PMID- 16589236
TI  - Abnormality of Down Pigmentation Associated with Experimentally Produced Skeletal
      Defects of Chicks.

PMID- 16589237
TI  - Evidence for the Synthesis of Vitamin B(12) by Spontaneous Tumors.

PMID- 16589238
TI  - New White Dwarfs in the Southern Hemisphere: Third List.

PMID- 16589239
TI  - A Kinetic Treatment of Saturation and Condensation Statistics.

PMID- 16589240
TI  - The High Field Conductance of Some Symmetrical Valence-Type Strong Electrolytes.

PMID- 16589241
TI  - The Basis of the Oxygen Effect on X-Irradiated Drosophila Sperm.

PMID- 16589242
TI  - The Genetics of Homeostasis in Drosophila.

PMID- 16589243
TI  - Heterogeneity of Clones of Saccharomyces Derived from Haploid Ascospores.

PMID- 16589244
TI  - Assumption of Boundary Values and the Green's Function in the Dirichlet Problem
      for the General Linear Elliptic Equation.

PMID- 16589245
TI  - Linear Parabolic Differential Equations of Arbitrary Order; General Boundary
      Value Problems for Elliptic Equations.

PMID- 16589247
TI  - A Property of Minimal Surfaces.

PMID- 16589246
TI  - Stochastic Processes with Finite and Non-Finite Variance.

PMID- 16589248
TI  - Second Order Elliptic Systems of Differential Equations.

PMID- 16589249
TI  - Spirals in the Plane.

PMID- 16589250
TI  - Homology Groups of Symmetric Groups and Reduced Power Operations.

PMID- 16589251
TI  - Cyclic Reduced Powers of Cohomology Classes.

PMID- 16589252
TI  - Oxidation of Intermediates of the Tricarboxylic Acid Cycle by Extracts of
      Azotobacter Agile.

PMID- 16589254
TI  - The Solubility of the Dimethyletherate of Aluminum Bromide in Methyl Bromide in
      the Presence of Saturated Hydrocarbons.

PMID- 16589253
TI  - A Biochemically Specific Method for Enzyme Isolation.

PMID- 16589255
TI  - The Potential Usefulness of Natural Tritium.

PMID- 16589256
TI  - Two Pleated-Sheet Configurations of Polypeptide Chains Involving Both Cis and
      Trans Amide Groups.

PMID- 16589257
TI  - Two Rippled-Sheet Configurations of Polypeptide Chains, and a Note about the
      Pleated Sheets.

PMID- 16589258
TI  - On the Inclination of Plastic Slip Bands in Flat Bars in Tension Tests.

PMID- 16589259
TI  - The Effect of Compressibility on the Inclination of Plastic Slip Bands in Flat
      Bars.

PMID- 16589260
TI  - Nonlinear Multipoles.

PMID- 16589261
TI  - A Study of Mutability in Streptomycin-Dependent Strains of Escherichia Coli.

PMID- 16589262
TI  - Induced Pollen Lethals from Seeds of Datura Stramonium Treated with Thermal
      Neutrons.

PMID- 16589263
TI  - The Effect of Thermal Neutron Radiation on the Chromosomes of Datura.

PMID- 16589264
TI  - On Some Variational Problems Occurring in the Theory of Dynamic Programming.

PMID- 16589265
TI  - Fourier Transforms of Time Series.

PMID- 16589266
TI  - On the Basis Theorem for Finite Abelian Groups: IV.

PMID- 16589267
TI  - Games with Equilibrium Points.

PMID- 16589268
TI  - On the Number of Husimi Trees: I.

PMID- 16589269
TI  - Studies in the Conformal Mapping of Riemann Surfaces: I.

PMID- 16589270
TI  - The Parametrisation and Element of Volume of the Unitary Symplectic Group.

PMID- 16589271
TI  - Heat Conduction on Arbitrary Riemannian Manifolds.

PMID- 16589272
TI  - Absolute Valued Algebras.

PMID- 16589273
TI  - An Analysis of the Synthesis and Distribution of the Contractile Protein, Myosin,
      in the Development of the Heart.

PMID- 16589274
TI  - The Structure of the Macronucleus of Paramecium Aurelia.

PMID- 16589275
TI  - Magellanic Clouds: VI. Revised Distances and Luminosities.

PMID- 16589276
TI  - Magellanic Clouds: VII. Star Colors and Luminosities in Five Constellations.

PMID- 16589277
TI  - Aromatic Biosynthesis: VI. Resistance to Inhibition by an Accumulated Metabolite,
      5-Dehydroshikimic Acid, and Its Significance for the Mechanism of Drug
      Resistance.

PMID- 16589278
TI  - The Effect of Ultraviolet Irradiation on Cell Division and Elongation in Timothy
      Roots.

PMID- 16589279
TI  - Enzymes, Specific Substrates and Competitive Inhibitors as Multifunctional
      Entities.

PMID- 16589280
TI  - Paper Chromatographic Patterns of Genetically Different Tissues: A Contribution
      to the Biochemical Study of Individuality.

PMID- 16589281
TI  - Alleles at a Mutable Locus Found in Populations of Wild House Mice (Mus
      Musculus).

PMID- 16589283
TI  - Serological Differentiation of the Homozygotes and Heterozygotes in Back-Cross
      Birds Following a Species Cross in Columbidae.

PMID- 16589282
TI  - Effects of Alkali Metal Ions on Development of Drosophila, with Special Reference
      to Lithium-Induced Abnormalities.

PMID- 16589284
TI  - Interaction Between Alleles Affecting Cellular Antigens Following a Species Cross
      in Columbidae.

PMID- 16589285
TI  - Genetic Exchange in Escherichia Coli K(12): Evidence for Three Linkage Groups.

PMID- 16589286
TI  - Effects of Temperature on Spontaneous and Induced Mutations in Escherichia Coli.

PMID- 16589288
TI  - On Differential Geometry in the Large.

PMID- 16589287
TI  - On the Eigenfunctions and Eigenvalues of the General Linear Elliptic Differential
      Operator.

PMID- 16589289
TI  - A Classical Model of a Roton.

PMID- 16589290
TI  - Serological Reactivity of Synthetic Polyglucoses.

PMID- 16589291
TI  - A New Particle Type in Certain Connective Tissue Extracts.

PMID- 16589292
TI  - Hydrogen Bonded Helical Configurations of the Polypeptide Chain.

PMID- 16589293
TI  - The Effect of a Suppressor on Allelic Inositolless Mutants in Neurospora Crossa.

PMID- 16589295
TI  - A Theory of N-Person Games with Perfect Information.

PMID- 16589294
TI  - The Effect of Pretreatment with Infra-Red Radiation on the X-ray Induced Sex
      Linked Recessive Lethal and Visible Mutation Rate in Drosophila Melanogaster.

PMID- 16589296
TI  - The Spinor Connection in the Unified Einstein Theory of Relativity.

PMID- 16589297
TI  - Connections Between Einstein's Two Unified Theories of Relativity.

PMID- 16589298
TI  - On the Contraction of Groups and Their Representations.

PMID- 16589300
TI  - Omnibus Checking of the 61-Place Table of Denary Logarithms Compiled by Peters
      and Stein, by Callet, and by Parkhurst.

PMID- 16589299
TI  - Ergodic Property of the Brownian Motion Process.

PMID- 16589301
TI  - Significance Levels for a Skew Distribution.

PMID- 16589302
TI  - Generalized Riemann Spaces and General Relativity.

PMID- 16589304
TI  - Equal Ratios of Energies of Nuclear Excited States of Even-Even Isotopes.

PMID- 16589303
TI  - A Theory of Ferromagnetism.

PMID- 16589305
TI  - The Effect Upon Heart Rate Conditioning of Randomly Varying the Interval Between
      Conditioned and Unconditioned Stimuli.

PMID- 16589306
TI  - The Effect of Antibiotics on Urea Breakdown in Mice.

PMID- 16589307
TI  - Path of Ornithine Synthesis in Escherichia Coli.

PMID- 16589308
TI  - Pulcherrimin, The Pigment of Candida Pulcherrima.

PMID- 16589309
TI  - Taxonomic Significance of Root-Hair Development in the Gramineae.

PMID- 16589310
TI  - The Molecular Weight of Some Long Chain Salts in Benzene by the Cryoscopic
      Method.

PMID- 16589311
TI  - Action of Boron Trifluoride Etherate on beta-Carotene.

PMID- 16589312
TI  - Mendelian and Non-Mendelian Factors Affecting the Cytochrome System in Neurospora
      Crassa.

PMID- 16589313
TI  - Induction of Chromosome Breakage at Meiosis by a Magnesium Deficiency in
      Tradescantia.

PMID- 16589314
TI  - Unity of the Vegetative Pool in Phage-Infected Bacteria.

PMID- 16589315
TI  - Induction of Mutations in a Bacterial Virus.

PMID- 16589316
TI  - Relations on Iterated Reduced Powers.

PMID- 16589317
TI  - Constrained Games and Linear Programming.

PMID- 16589318
TI  - On Arithmetic Genera of Algebraic Varieties.

PMID- 16589319
TI  - Extension Theorems for Solutions of Irreflexive Relations.

PMID- 16589320
TI  - A First Approximation to Homotopy Theory.

PMID- 16589321
TI  - Cohomology and the Riemann-Roch Theorem.

PMID- 16589322
TI  - Image Theory of Superposed Vector Sets.

PMID- 16589323
TI  - Solution Functions for Solving Superposed Patterson Syntheses.

PMID- 16589324
TI  - An Intersection Function and Its Relations to the Minimum Function of X-Ray
      Crystallography.

PMID- 16589325
TI  - About Space-Time Asymmetry in the Realm of Classical General and Crystal Physics.

PMID- 16589326
TI  - Action Potentials from an Arthropod Ocellus: The Median Eye of Limulus.

PMID- 16589327
TI  - Frequency of Separation and of Interlocking of Clusters of Galaxies.

PMID- 16589328
TI  - The Influence of Temperature Upon the Inactivation of a Bacterial Virus By X
      Rays.

PMID- 16589329
TI  - Electron Microscopy of the Nucleic Acid Released from Individual Bacteriophage
      Particles.

PMID- 16589330
TI  - Transfer of C By Lupine Mitochondria Through Reactions of the Tricarboxylic Acid
      Cycle.

PMID- 16589331
TI  - Subcellular Fractionation of Mouse Spleen Radiation Protection Activity.

PMID- 16589332
TI  - The Mechanism of Propionic Acid Formation by Succinate Decarboxylation: I. The
      Activation of Succinate.

PMID- 16589333
TI  - The Mechanism of Propionic Acid Formation by Succinate Decarboxylation: II. The
      Formation and Decarboxylation of Succinyl-CoA.

PMID- 16589334
TI  - Generalized Mathematical Relationships for Polypeptide Chain Helices: The
      Coordinates of the II Helix.

PMID- 16589335
TI  - Conductance and Viscosity of Concentrated Aqueous Salt Solutions at 50.5 degrees.

PMID- 16589336
TI  - Development and Genetics of a Sex-Influenced Trait in the Livers of Mice.

PMID- 16589337
TI  - Mutation Rates and Lethal Gene Frequencies in Populations of Drosophila
      Melanogaster.

PMID- 16589338
TI  - Anti-f and the "New" Rh Antigen it Defines.

PMID- 16589339
TI  - Further Studies on the Effects of Carbon Dioxide and Oxygen on the Frequency of X
      Ray Induced Chromosome Aberrations in Tradescantia.

PMID- 16589341
TI  - Travel Times of Longitudinal Waves From Surface Foci.

PMID- 16589340
TI  - Gene Action in Relation to Growth and Development: I. Phenotypic Variability.

PMID- 16589342
TI  - Approximate Methods in Mathematics.

PMID- 16589343
TI  - Ergodic Theory of Markov Chains Admitting an Infinite Invariant Measure.

PMID- 16589345
TI  - Groups of Complex Line Bundles Over Compact Kahler Varieties.

PMID- 16589344
TI  - On Cohomology Groups of Compact Analytic Varieties with Coefficients in Some
      Analytic Faisceaux.

PMID- 16589346
TI  - Divisor Class Groups on Algebraic Varieties.

PMID- 16589347
TI  - The Growth of Amblystoma Chimeras.

PMID- 16589348
TI  - Development of the Fine Structure of the Myelin Sheath in Sciatic Nerves of Chick
      Embryos.

PMID- 16589349
TI  - Acoustic Orientation in the Oil Bird, Steatornis.

PMID- 16589350
TI  - Alteration of the Kinetic Properties of an Enzyme by the Binding of Buffer,
      Inhibitor, or Substrate.

PMID- 16589351
TI  - A Light Activation Phenomenon in the Enzymatic and Nonenzymatic Reduction of
      Tetrazolium Salts.

PMID- 16589352
TI  - The Interaction of Auxin and Light in the Growth Responses of Plants.

PMID- 16589353
TI  - The Conductance of Solutions of Salts in Orthodichlorobenzene.

PMID- 16589354
TI  - The Effect of Indole-3-Acetic Acid on Datura Embryos.

PMID- 16589355
TI  - On the Origin of Continents and Mountains.

PMID- 16589356
TI  - Bottleneck Problems and Dynamic Programming.

PMID- 16589357
TI  - On Steenrod's Reduced Powers, the Index of Inertia, and the Todd Genus.

PMID- 16589358
TI  - The Ideas of Variable and Function.

PMID- 16589359
TI  - Pairs of Matrices with Property L.

PMID- 16589360
TI  - On Restricted Partitions and a Generalization of the Euler phi Number and the
      Moebius Function.

PMID- 16589361
TI  - Characterization of Quadratic Forms Over Local Fields.

PMID- 16589362
TI  - The Axiom of Choice in Quine's New Foundations for Mathematical Logic.

PMID- 16589363
TI  - Nuclear Reactions with Energetic Nitrogen Ions.

PMID- 16589364
TI  - The Differentiation of Gastrula Ectoderm in Medium Conditioned by Axial Mesoderm.

PMID- 16589365
TI  - Acetylation of Glutamic Acid by Extracts of Escherichia Coli.

PMID- 16589366
TI  - Release of Mitochondria from Yeast Cells by the Action of Metal-Chelating Agents.

PMID- 16589367
TI  - The Role of the Tricarboxylic Acid Cycle in Amino Acid Synthesis in Escherichia
      Coli.

PMID- 16589368
TI  - Synthesis of the Aspartic and Glutamic Families of Amino Acids in Escherichia
      Coli.

PMID- 16589369
TI  - Indispensable Gene Functions in Neurospora.

PMID- 16589370
TI  - Immunogenetic Studies of Pseudoallelism in Drosophila Melanogaster.

PMID- 16589371
TI  - A Relationship of Homocysteine Metabolism to Thiamin, Serine, and Adenine
      Biosynthesis in a Mutant Strain of Neurospora.

PMID- 16589372
TI  - Induced Host-Range Mutations in Bacteriophage.

PMID- 16589373
TI  - Mating Type Determination in Tetrahymena Pyriformis.

PMID- 16589374
TI  - The Effect of the Previous Generation on the Distribution of Gene Frequencies in
      Populations.

PMID- 16589375
TI  - A General Principle Involving Baire Category, with Applications to Function
      Theory and Other Fields.

PMID- 16589376
TI  - On A Generalization of Classical Probability Theory: I. Markoff Chains.

PMID- 16589377
TI  - Some Functional Equations in the Theory of Dynamic Programming.

PMID- 16589378
TI  - Closure Classes Originating in the Theory of Probability.

PMID- 16589379
TI  - Completely Integrable Partial Differential Equations in Normed Linear Spaces.

PMID- 16589381
TI  - Existence of Generalized Local Class Fields.

PMID- 16589380
TI  - Stochastic Games.

PMID- 16589382
TI  - A Selective Staining Method for the Basic Proteins of Cell Nuclei.

PMID- 16589383
TI  - The Evaluation of the Kinetic Constants of Enzyme Catalyzed Reactions.

PMID- 16589384
TI  - A Theory of Auxin Action Involving Coenzyme A.

PMID- 16589385
TI  - Experimental Coupling of Indoleacetic Acid to Pea Root Protein In Vivo and In
      Vitro.

PMID- 16589386
TI  - The Viscosity and the Conductance-Viscosity Product of Electrolyte Solutions in
      Bromine.

PMID- 16589387
TI  - The Effects of Temperature on Ultraviolet-Induced Mutability in Escherichia Coli.

PMID- 16589388
TI  - The Effects of Infra-Red Radiation and Desiccation on Crossingover in Drosophila
      Melanogaster.

PMID- 16589389
TI  - Homology and Cohomology of Compact Connected Lie Groups.

PMID- 16589390
TI  - Ascites Tumor-Virus System as a Biological Tool.

PMID- 16589391
TI  - The Development of Transplanted Fragments of Fundulus Gastrulae.

PMID- 16589393
TI  - Note on the Origin of the Asteroids.

PMID- 16589392
TI  - Satellites, Comets, and Interplanetary Material.

PMID- 16589394
TI  - Magellanic Clouds: VIII. On the Population Characteristics of the Two Clouds.

PMID- 16589395
TI  - Magellanic Clouds: IX. The Nebulosities of the Small Coud.

PMID- 16589396
TI  - The Enzymatic Synthesis of Porphyrins from Porphobilinogen.

PMID- 16589397
TI  - Competition Among Ionic Species in Cation Activation of Enzymes.

PMID- 16589398
TI  - Enzymatic Reactions in Purine Decomposition by Preparations of Clostridium Acidi
      Urici.

PMID- 16589399
TI  - Effect of Amino Acids, Especially Asrartic and Glutamic Acid and Their Amides, on
      the Growth of Datura Stramonium Embryos in Vitro.

PMID- 16589400
TI  - The Behavior of Micellar Electrolytes in the Neighborhood of the Critical
      Concentration.

PMID- 16589401
TI  - On the Effect of Pretwisting on Bending.

PMID- 16589402
TI  - The Effect of Generation Time on the Delayed Appearance of Induced Mutants in
      Escherichia Coli.

PMID- 16589403
TI  - The Relationship between Kappa and Paramecin in Paramecium Aurelia.

PMID- 16589404
TI  - Cross Reactivation of Genetic Loci of T2 Bacteriophage after Decay of
      Incorporated Radioactive Phosphorus.

PMID- 16589405
TI  - Effect of X-Rays on Chromatid Aberrations in Air and in Nitrogen.

PMID- 16589406
TI  - Spiral and Other Asymptotic Paths, and Paths of Complete Indetermination, of
      Analytic and Meromorphic Functions.

PMID- 16589407
TI  - The Global Behavior of Differential Equations on N-Dimensional Manifolds.

PMID- 16589408
TI  - Conjugate Nets, Conformal Structure, and Interior Transformations on Open Riemann
      Surfaces.

PMID- 16589409
TI  - On a Differential-Geometric Method in the Theory of Analytic Stacks.

PMID- 16589410
TI  - On a Theorem of Lefschetz and the Lemma of Enriques-Severi-Zariski.

PMID- 16589411
TI  - On a New Problem Concerning Trinomial Congruences Involving Rational Integers.

PMID- 16589412
TI  - Mechanochemical Properties of Fibers of Surface-Spread Actomyosin.

PMID- 16589413
TI  - Phosphomonoesterases in Reef-Building Corals.

PMID- 16589414
TI  - Vital Statistics of our Foreign Associates.

PMID- 16589415
TI  - MAGELLANIC CLOUDS, X. AN EVALUATION OF THE ZERO POINT CORRECTION.

PMID- 16589416
TI  - THE LUMINESCENT OXIDATION OF REDUCED RIBOFLAVIN OR REDUCED RIBOFLAVIN PHOSPHATE
      IN THE BACTERIAL LUCIFERIN-LUCIFERASE REACTION.

PMID- 16589417
TI  - THE INFRARED ASSOCIATION SPECTRA OF AMIDES IN SOLUTION AND THEIR RELATION TO THE
      SPECTRA OF POLYPEPTIDES.

PMID- 16589418
TI  - THE SOLUBILITY OF HYDROCARBONS IN WATER.

PMID- 16589419
TI  - ON THE INTEGRATION OF KOLMOGOROFF'S DIFFERENTIAL EQUATIONS.

PMID- 16589421
TI  - GEODESIC FLOWS AND UNITARY REPRESENTATIONS.

PMID- 16589420
TI  - AN APPLICATION OF HIGH-SPEED COMPUTING TO FERMAT'S LAST THEOREM.

PMID- 16589423
TI  - ENVIRONMENTAL RELATIONS OF MODIFICATION COMPOSITIONS OF CERTAIN CARBONATE
      SECRETING MARINE INVERTEBRATES.

PMID- 16589422
TI  - ORAL ADMINISTRATION OF POLIOMYELITIS VIRUS TO MAN AND APE-A COMPARATIVE STUDY.

PMID- 16589424
TI  - INACTIVATION AND REACTIVATION OF B. MEGATHERIUM PHAGE.

PMID- 16589425
TI  - SOME PHYSICAL CHEMICAL EXPERIMENTS WITH HEMOGLOBINS FROM NORMAL AND GENETICALLY
      ANEMIC MICE.

PMID- 16589426
TI  - ARITHMETIC GENERA AND THE THEOREM OF RIEMANN-ROCH FOR ALGEBRAIC VARIETIES.

PMID- 16589427
TI  - ON THE CONTINUOUS GOLD-MINING EQUATION.

PMID- 16589429
TI  - ON NON-NEGATIVE-VALUED MATRICES.

PMID- 16589428
TI  - ON A PARTICULAR TYPE OF CONVERGENCE TO A SINGULAR MATRIX.

PMID- 16589430
TI  - SOME RELATIONS FOR CRYSTALS WITH SUBSTRUCTURES.

PMID- 16589431
TI  - ON DIFFRACTION BY A STRIP.

PMID- 16589432
TI  - THE QUANTUM CORRECTION IN THE RADIATION BY ENERGETIC ACCELERATED ELECTRONS.

PMID- 16589433
TI  - CYCLICAL BEHAVIOR IN PNEUMOCOCCAL GROWTH AND TRANSFORMABILITY OCCASIONED BY
      ENVIRONMENTAL CHANGES.

PMID- 16589434
TI  - DOUBLE MARKER TRANSFORMATIONS AS EVIDENCE OF LINKED FACTORS IN DESOXYRIBONUCLEATE
      TRANSFORMING AGENTS.

PMID- 16589435
TI  - THE ISOLATION AND IDENTIFICATION OF THE MAJOR ANION FRACTION OF THE AXOPLASM OF
      SQUID GIANT NERVE FIBERS.

PMID- 16589436
TI  - DIELECTRIC INCREMENTS IN AQUEOUS SOLUTIONS OF SYNTHETIC POLYELECTROLYTES.

PMID- 16589438
TI  - SONIC POINT ON SUPERSONIC AIRFOILS.

PMID- 16589437
TI  - THE RATES OF REACTION BETWEEN ALKYL HALIDES AND TERTIARY AMINES AS DETERMINED
      CONDUCTOMETRICALLY.

PMID- 16589439
TI  - REAR SHOCK AND PRESSURE ON SUPERSONIC AIRFOILS.

PMID- 16589440
TI  - GENETIC CHANGES IN AMERICAN POPULATIONS OF DROSOPHILA MELANOGASTER.

PMID- 16589441
TI  - PSEUDO-ALLELISM AT THE VERMILION LOCUS IN DROSOPHILA MELANOGASTER.

PMID- 16589442
TI  - NUMERICAL PREDICTION OF CYCLOGENESIS.

PMID- 16589443
TI  - NEW WHITE DWARFS IN THE SOUTHERN HEMISPHERE: FOURTH LIST.

PMID- 16589444
TI  - RELATION OF POLYPHENOL OXIDASES TO FUNGITOXICITY.

PMID- 16589445
TI  - A REFINEMENT OF THE PAULING THEORY OF FERROMAGNETISM.

PMID- 16589446
TI  - ON MOST PROBABLE DISTRIBUTIONS.

PMID- 16589447
TI  - RECENT TECHNICAL MANIFESTATIONS OF VON KARMAN'S VORTEX WAKE.

PMID- 16589448
TI  - HIGH-STRENGTH PLASTICS.

PMID- 16589449
TI  - THE EFFECTS OF DNA AND ENZYME-TREATED DNA ON BACTERIAL POPULATION CHANGES.

PMID- 16589450
TI  - THE PRODUCTION OF MUTATIONS IN DROSOPHILA MELANOGASTER BY THE FAST NEUTRON
      RADIATION OF AN ATOMIC EXPLOSION.

PMID- 16589451
TI  - PROTECTIVE PROPERTIES OF CYSTEINE, SODIUM HYPOSULFITE, AND SODIUM CYANIDE AGAINST
      RADIATION INDUCED CHROMOSOME ABERRATIONS.

PMID- 16589452
TI  - THE DELAYED APPEARANCE OF MUTANTS IN BACTERIAL CULTURES.

PMID- 16589453
TI  - INDEPENDENT X-RAY EFFECTS ON CHROMOSOME BREAKAGE AND REUNION.

PMID- 16589454
TI  - THE SEPARATION AND ISOLATION OF PARTICULAR BIOCHEMICAL MUTANTS OF NEUROSPORA BY
      DIFFERENTIAL GERMINATION OF CONIDIA, FOLLOWED BY FILTRATION AND SELECTIVE
      PLATING.

PMID- 16589456
TI  - PROOF OF A CONJECTURE OF STEINHAUS.

PMID- 16589455
TI  - ON THE PLANCHEREL FORMULA FOR THE RIGHT-INVARIANT FUNCTIONS ON A SEMISIMPLE LIE
      GROUP.

PMID- 16589457
TI  - ON CERTAIN INEQUALITIES RELATING THE BETTI NUMBERS OF A MANIFOLD AND ITS SUBSETS.

PMID- 16589458
TI  - THE PHASE CHARACTERISTICS OF THE EAR.

PMID- 16589459
TI  - CONFERENCE ON BIOCHEMISTRY, PALEOECOLOGY, AND EVOLUTION.

PMID- 16589460
TI  - THE INHIBITION OF HYDROGENASE BY NITRIC OXIDE.

PMID- 16589461
TI  - A BIOCHEMICAL AND PHARMACOLOGICAL SUGGESTION ABOUT CERTAIN MENTAL DISORDERS.

PMID- 16589462
TI  - DYNAMIC PROGRAMMING AND A NEW FORMALISM IN THE CALCULUS OF VARIATIONS.

PMID- 16589463
TI  - A CHARACTERIZATION OF TAME CURVES IN THREE-SPACE.

PMID- 16589464
TI  - CONFORMAL GEOMETRY AND ELEMENTARY PARTICLES.

PMID- 16589465
TI  - APPROXIMATION BY BOUNDARY VALUES OF ANALYTIC FUNCTIONS.

PMID- 16589466
TI  - A NOTE ON THE ABSTRACT CAUCHY PROBLEM.

PMID- 16589467
TI  - NEW TYPES OF TRINOMIAL CONGRUENCE CRITERIA APPLYING TO FERMAT'S LAST THEOREM.

PMID- 16589468
TI  - DIRECTIONAL SENSITIVITY OF SINGLE OMMATIDIA IN THE COMPOUND EYE OF LIMULUS.

PMID- 16589469
TI  - POLARIZED LIGHT AND ANGLE OF STIMULUS INCIDENCE IN THE COMPOUND EYE OF LIMULUS.

PMID- 16589470
TI  - NUCLEIC ACID PRECURSORS AND PROTEIN SYNTHESIS.

PMID- 16589471
TI  - SYNTHESIS OF AROMATIC COMPOUNDS BY NEUROSPORA.

PMID- 16589472
TI  - EFFECT OF LOCAL-ACTION CURRENTS ON THE IRON POTENTIAL.

PMID- 16589473
TI  - THE NATURAL C CONTENTS OF MATERIALS FROM HARD-WATER LAKES.

PMID- 16589474
TI  - BOUNDEDNESS AND STATIONARITY OF TIME SERIES.

PMID- 16589475
TI  - ANALYTIC ALMOST-PERIODIC FUNCTIONS. I.

PMID- 16589476
TI  - POLYADIC BOOLEAN ALGEBRAS.

PMID- 16589477
TI  - STUDIES IN THE CONFORMAL MAPPING OF RIEMANN SURFACES. II.

PMID- 16589478
TI  - ON THE LIE RING OF A SIMPLE RING.

PMID- 16589479
TI  - ON A THEOREM BY MURNAGHAN.

PMID- 16589480
TI  - ON THE ARITHMETIC NORMALITY OF THE GRASSMANN VARIETY.

PMID- 16589481
TI  - ON KAHLER VARIETIES OF RESTRICTED TYPE.

PMID- 16589483
TI  - DETERMINATION OF THE PLASTIC YIELD CONDITION AS A VARIATIONAL PROBLEM.

PMID- 16589482
TI  - ON THE DERIVATION OF THE EQUATIONS OF HYDRODYNAMICS FROM STATISTICAL MECHANICS.

PMID- 16589484
TI  - NOTE ON THE DISTRIBUTION OF ZEROS OF EXTREMAL POLYNOMIALS.

PMID- 16589485
TI  - THE EFFECTS OF CHORIOALLANTOIC TRANSPLANTS OF ADULT CHICKEN TISSUES ON HOMOLOGOUS
      TISSUES OF THE HOST CHICK EMBRYO.

PMID- 16589486
TI  - NEURAL BASIS OF DIURNAL PERIODICITY IN RELEASE OF OVULATION-INDUCING HORMONE IN
      FOWL.

PMID- 16589487
TI  - MENDELIAN AND NON-MENDELIAN INHERITANCE OF STREPTOMYCIN RESISTANCE IN
      CHLAMYDOMONAS REINHARDI.

PMID- 16589488
TI  - MAGELLANIC CLOUDS. XI. SURVEY OF THE NOVAE.

PMID- 16589489
TI  - MAGELLANIC CLOUDS. XII. OBSERVATIONS OF A NOVA IN THE SMALL CLOUD.

PMID- 16589490
TI  - MECHANISM OF ACQUIRED IMMUNITY TO A PLANT RUST.

PMID- 16589491
TI  - RADIAL DISTRIBUTION FUNCTIONS OF SOME STRUCTURES OF THE POLYPEPTIDE CHAIN.

PMID- 16589492
TI  - DEVIATION OF AQUEOUS ELECTROLYTE SOLUTIONS FROM ONSAGER'S EQUATION.

PMID- 16589494
TI  - PLASTIC FLOW IN THE CUTTING AND GRINDING OF MATERIALS.

PMID- 16589493
TI  - THE DYNAMIC ANALYSIS OF LOW-ASPECT-RATIO AIRPLANE WINGS.

PMID- 16589495
TI  - ON THE ROTATION OF GRID LINES PRODUCED BY THE FORMATION OF PLASTIC BANDS IN
      TENSION TESTS.

PMID- 16589496
TI  - ENVIRONMENTAL MODIFICATION OF HETEROSIS IN DROSOPHILA PSEUDOOBSCURA.

PMID- 16589497
TI  - POSTZYGOTIC ELIMINATION OF GENETIC FACTORS IN ESCHERICHIA COLI.

PMID- 16589498
TI  - EVIDENCE FOR ACTIVELY ACQUIRED TOLERANCE TO Rh ANTIGENS.

PMID- 16589499
TI  - ON THE NATURE OF THE EMBRYO INHIBITOR IN OVULAR TUMORS OF DATURA.

PMID- 16589500
TI  - SOMATIC MUTATIONS IN THE CARNATION, DIANTHUS CARYOPHYLLUS L.

PMID- 16589501
TI  - A PARTIAL MAP OF LINKAGE GROUP D IN NEUROSPORA CRASSA.

PMID- 16589502
TI  - INDUCED POLLEN LETHALS FROM SEEDS OF DATURA STRAMONIUM EXPOSED TO RADIATION FROM
      A NUCLEAR DETONATION.

PMID- 16589504
TI  - BOUNDS FOR DETERMINANTS.

PMID- 16589503
TI  - THE EFFECTS OF FAST-NEUTRON RADIATION FROM A NUCLEAR DETONATION ON CHROMOSOME
      ABERRATION IN DATURA.

PMID- 16589505
TI  - THE EIGENFUNCTION EXPANSION THEOREM FOR THE GENERAL SELF-ADJOINT SINGULAR
      ELLIPTIC PARTIAL DIFFERENTIAL OPERATOR. I. THE ANALYTICAL FOUNDATION.

PMID- 16589506
TI  - EIGENFUNCTION EXPANSIONS FOR SINGULAR ELLIPTIC OPERATORS. II. THE HILBERT SPACE
      ARGUMENT; PARABOLIC EQUATIONS ON OPEN MANIFOLDS.

PMID- 16589507
TI  - GENERALIZED RIEMANN SPACES AND GENERAL RELATIVITY. II.

PMID- 16589508
TI  - SUR LES GROUPES D'EILENBERG-MAC LANE H(II, n): I. METHODE DES CONSTRUCTIONS.

PMID- 16589509
TI  - TOPOLOGICAL VECTOR SPACES OF CONTINUOUS FUNCTIONS.

PMID- 16589510
TI  - THE RELATION OF SOME DATA OBTAINED FROM RAPID COMPUTING MACHINES TO THE THEORY OF
      CYCLOTOMIC FIELDS.

PMID- 16589511
TI  - ON THE FORMATION OF PROTOGALAXIES IN THE TURBULENT PRIMORDIAL GAS.

PMID- 16589512
TI  - ON THE PROGRAM OF A SYSTEMATIZATION OF PARTICLES AND INTERACTIONS.

PMID- 16589513
TI  - THE BIOSYNTHESIS OF ISOLEUCINE AND VALINE. I. ENZYMATIC TRANSFORMATION OF THE
      DIHYDROXY ACID PRECURSORS TO THE KETO ACID PRECURSORS.

PMID- 16589514
TI  - A NONENZYMATIC ILLUSTRATION OF "CITRIC ACID TYPE" ASYMMETRY: THE MESO-CARBON
      ATOM.

PMID- 16589515
TI  - A NOTE ON RECENT DEVELOPMENTS IN AUDITORY THEORY.

PMID- 16589516
TI  - SOLUBILITY OF PROTYROSINASE AND TYROSINASE.

PMID- 16589517
TI  - OVARIAN HORMONES AND THE IONIC BALANCE OF UTERINE MUSCLE.

PMID- 16589518
TI  - THE PARTICULATE ORGANIZATION OF THE CHROMOSOME.

PMID- 16589519
TI  - ELECTRON-MICROSCOPIC STUDY OF THE TEXTURE OF THE BASEMENT MEMBRANE OF LARVAL
      AMPHIBIAN SKIN.

PMID- 16589521
TI  - MAGELLANIC CLOUDS. XIII. COMPARISON OF MAGELLANIC AND GALACTIC ECLIPSING
      VARIABLES.

PMID- 16589520
TI  - FLUCTUATIONS IN THE SPACE DISTRIBUTION OF THE GALAXIES.

PMID- 16589522
TI  - THE DIFFUSION COEFFICIENTS OF THE ALKALI METAL CHLORIDES AND POTASSIUM AND SILVER
      NITRATES IN DILUTE AQUEOUS SOLUTIONS AT 25 degrees.

PMID- 16589523
TI  - THE SHOCK TUBE IN AERODYNAMIC AND STRUCTURAL RESEARCH.

PMID- 16589524
TI  - GRID ROTATION IN LUDERS BANDS.

PMID- 16589526
TI  - THE RELATION BETWEEN X-RAY DOSAGE AND THE FREQUENCY OF SIMULATED HEALING OF
      CHROMOSOME BREAKAGES IN DROSOPHILA MELANOGASTER FEMALES.

PMID- 16589525
TI  - A DISCUSSION OF THE LOAD DROP AND RELATED MATTERS ASSOCIATED WITH THE FORMATION
      OF A LUDERS BAND.

PMID- 16589527
TI  - ON TORSION IN LIE GROUPS.

PMID- 16589528
TI  - VALUATION EQUILIBRIUM AND PARETO OPTIMUM.

PMID- 16589529
TI  - INTERDEPENDENCE OF THE YIELD CONDITION AND THE STRESS-STRAIN RELATIONS FOR
      PLASTIC FLOW.

PMID- 16589530
TI  - A GENERALIZATION OF THE FRECHET DISTANCE OF TWO CURVES.

PMID- 16589531
TI  - ESTIMATION OF THE COMPONENTS OF STOCHASTIC STRUCTURES.

PMID- 16589533
TI  - REPRESENTATIONS OF THE ANTICOMMUTATION RELATIONS.

PMID- 16589532
TI  - THE TEMPERATURE-PRESSURE-INHIBITOR RELATIONS OF BACTERIAL LUMINESCENCE IN VITRO.

PMID- 16589534
TI  - REPRESENTATIONS OF THE COMMUTATION RELATIONS.

PMID- 16589535
TI  - NOTE ON A "PERMANENT" EXPERIMENTAL ALTERATION OF GENETIC CONSTITUTION IN A
      NATURAL POPULATION.

PMID- 16589536
TI  - NATIONAL ACADEMY OF SCIENCES: July 1, 1954.

PMID- 16589537
TI  - THE EFFECT OF DIABETES AND FASTING ON LIVER GLUCOSE-6-PHOSPHATASE.

PMID- 16589538
TI  - COLLAGEN STRUCTURES CONSIDERED AS STATES OF AGGREGATION OF A KINETIC UNIT. THE
      TROPOCOLLAGEN PARTICLE.

PMID- 16589539
TI  - ON THE GLUTAMATE-PROLINE-ORNITHINE INTERRELATION IN NEUROSPORA CRASSA.

PMID- 16589540
TI  - CAROTENOID DIFFERENCES IN LYCOPERSICON: HYBRIDS OF AN UNUSUAL RACE OF L.
      PIMPINELLIFOLIUM.

PMID- 16589541
TI  - LIMIT THEOREMS FOR HOMOGENEOUS STOCHASTIC PROCESSES.

PMID- 16589542
TI  - SUR LES GROUPES D'EILENBERG-MAC LANE. II.

PMID- 16589543
TI  - A NONLINEAR DIFFERENTIAL-DIFFERENCE EQUATION OF GROWTH.

PMID- 16589544
TI  - A NEW CLASS OF SIMPLE LIE ALGEBRAS.

PMID- 16589545
TI  - GENERAL EXISTENCE AND UNIQUENESS PROOF FOR SPATIALLY HOMOGENEOUS SOLUTIONS OF THE
      MAXWELL-BOLTZMANN EQUATION IN THE CASE OF MAXWELLIAN MOLECULES.

PMID- 16589546
TI  - ON THE ANALYSES OF {m} [unk] {1} AND {m} [unk] {k}.

PMID- 16589547
TI  - THE REDUCTION OF THE INNER PRODUCT OF TWO IRREDUCIBLE REPRESENTATIONS OF S(n).

PMID- 16589548
TI  - ON A CLASS OF SEMISIMPLE RESTRICTED LIE ALGEBRAS.

PMID- 16589550
TI  - EXAMINATION OF METHODS OF ATTACK ON THE SECOND CASE OF FERMAT'S LAST THEOREM.

PMID- 16589549
TI  - HAMARTIEXERESIS AS APPLIED TO TABLES INVOLVING LOGARITHMS.

PMID- 16589551
TI  - THE AGGLUTINATING AND SENSITIZING CAPACITY OF ANTISERA TO SHEEP RED CELLS AFTER
      VARYING DEGREES OF PHOTO-OXIDATION.

PMID- 16589552
TI  - SOME PHYSICAL ASPECTS OF THE STABILITY OF PARALLEL FLOWS.

PMID- 16589553
TI  - CHEMICAL STRUCTURE OF THE NUCLEIC ACIDS.

PMID- 16589554
TI  - THE COMPLEMENTARY STRUCTURE OF DNA.

PMID- 16589555
TI  - SOME RELATIONS BETWEEN DNA AND RNA.

PMID- 16589556
TI  - BIOSYNTHESIS OF NUCLEIC ACID IN ESCHERICHIA COLI.

PMID- 16589557
TI  - GLUCOSAMINE KINASE OF SCHISTOSOMA MANSONI.

PMID- 16589558
TI  - DIFFERENTIAL TITRATION BY MEANS OF PAPER ELECTROPHORESIS AND THE STRUCTURE OF
      HUMAN HEMOGLOBINS.

PMID- 16589560
TI  - THE VAPOR PRESSURE OF SMALL DROPS.

PMID- 16589559
TI  - ON THE REPLICATION OF DESOXYRIBONUCLEIC ACID (DNA).

PMID- 16589561
TI  - COMMENTS ON A "MESO-CARBON ATOM".

PMID- 16589562
TI  - RADIATION-INDUCED EXCHANGES IN DROSOPHILA FEMALES.

PMID- 16589563
TI  - GLOBAL VERSIONS OF THE CENTRAL LIMIT THEOREM.

PMID- 16589564
TI  - ON THE QUOTIENT OF AN ANALYTIC MANIFOLD BY A GROUP OF ANALYTIC HOMEOMORPHISMS.

PMID- 16589565
TI  - ON EXTREMAL QUASI-CONFORMAL MAPPINGS. I.

PMID- 16589566
TI  - REGRESSION ANALYSIS OF TIME SERIES WITH STATIONARY RESIDUALS.

PMID- 16589567
TI  - ON POSITIVE GREEN'S FUNCTIONS.

PMID- 16589568
TI  - A SIMPLE DEFINITION OF ANALYTIC FUNCTIONS AND GENERAL MULTIFUNCTIONS.

PMID- 16589569
TI  - ON THE SYMMETRY PROPERTIES OF POWERS OF REPRESENTATIONS OF THE TWO-DIMENSIONAL
      UNIMODULAR UNITARY GROUP.

PMID- 16589570
TI  - A VON STERNECK ARITHMETICAL FUNCTION AND RESTRICTED PARTITIONS WITH RESPECT TO A
      MODULUS.

PMID- 16589571
TI  - SPHERICAL SPINORS IN A EUCLIDEAN 4-SPACE.

PMID- 16589572
TI  - A REMARK ON THE EXTREMAL DISTANCE OF TWO BOUNDARY COMPONENTS.

PMID- 16589573
TI  - IRREVERSIBLE SYSTEMS, ENTROPY, AND RIEMANN SPACES.

PMID- 16589574
TI  - HIGH-TONE STIMULATION AND HEARING LOSS.

PMID- 16589575
TI  - A QUANTITATIVE THEORY OF VISUAL EXCITATION FOR THE SINGLE PHOTORECEPTOR.

PMID- 16589576
TI  - THE STRUCTURE OF THE SCHWANN CELL AND ITS RELATION TO THE AXON IN CERTAIN
      INVERTEBRATE NERVE FIBERS.

PMID- 16589577
TI  - NOTE ON A PAPER BY MURNAGHAN.

PMID- 16589579
TI  - A NOTE ON THE ENUMERATION AND LISTING OF ALL POSSIBLE TREES IN A CONNECTED LINEAR
      GRAPH.

PMID- 16589578
TI  - A REMARK ON DETACHED SHOCKS.

PMID- 16589580
TI  - ON TRINOMIAL EQUATIONS IN A FINITE FIELD.

PMID- 16589581
TI  - A SECOND GENERALIZATION OF THE FRECHET DISTANCE OF TWO CURVES.

PMID- 16589582
TI  - A NERVE GROWTH-STIMULATING FACTOR ISOLATED FROM SARCOM AS 37 AND 180.

PMID- 16589583
TI  - ON TEMPERATURE INDEPENDENCE IN THE CLOCK SYSTEM CONTROLLING EMERGENCE TIME IN
      DROSOPHILA.

PMID- 16589584
TI  - SPATIAL DISTRIBUTION OF GALAXIES-ANALYSIS OF THE THEORY OF FLUCTUATIONS.

PMID- 16589585
TI  - AMINO ACID INCORPORATION BY ISOLATED THYMUS NUCLEI. I. THE ROLE OF
      DESOXYRIBONUCLEIC ACID IN PROTEIN SYNTHESIS.

PMID- 16589586
TI  - STUDIES ON UNBALANCED GROWTH IN ESCHERICHIA COLI.

PMID- 16589587
TI  - ON THE MACROMOLECULAR STRUCTURE OF DEOXYRIBONUCLEIC ACID: AN INTERRUPTED TWO
      STRAND MODEL.

PMID- 16589588
TI  - THE UNCOUPLING OF RESPIRATION AND PHOSPHORYLATION BY THYROID HORMONES.

PMID- 16589589
TI  - ON THE FLOW OF A PERFECT FLUID THROUGH A POLYGONAL NOZZLE. I.

PMID- 16589590
TI  - ON THE FLOW OF A PERFECT FLUID THROUGH A POLYGONAL NOZZLE. II.

PMID- 16589591
TI  - HARMONIC MAPPINGS.

PMID- 16589592
TI  - ON EXTREMAL QUASI-CONFORMAL MAPPINGS. II.

PMID- 16589593
TI  - THE DERIVED ALGEBRA OF A BANACH ALGEBRA.

PMID- 16589594
TI  - ON THE MEAN INVERSION OF FOURIER AND HANKEL TRANSFORMS.

PMID- 16589595
TI  - Interstellar Hydrogen and the Local System.

PMID- 16589596
TI  - On the Origin of the Lunar Surface Features.

PMID- 16589597
TI  - The Role of Nutrition in the Host-Parasite Relationship.

PMID- 16589598
TI  - The Relation between Modulator and Activator in Maize.

PMID- 16589599
TI  - An Allele of the S(s) Blood Group Genes.

PMID- 16589600
TI  - Chromosome Shattering by Ultraviolet Radiation (2650 A).

PMID- 16589601
TI  - The Nature of the Pigment Induced by Chromogenic Inductors of Serratia
      Marcescens.

PMID- 16589602
TI  - The Effects of Pre- and Postirradiation Centrifugation on the Chromosomes of
      Tradescantia and Vicia.

PMID- 16589603
TI  - Positive Zonal Functions on Spheres.

PMID- 16589604
TI  - Kahlerian Coset Spaces of Semisimple Lie Groups.

PMID- 16589605
TI  - The Green's and Neumann's Problems for Differential Forms on Riemannian
      Manifolds.

PMID- 16589606
TI  - Ergodic Property of the Brownian Motion Process.

PMID- 16589607
TI  - On the Possibility of Electromagnetic Surface Waves.

PMID- 16589609
TI  - A TEST FOR RECOMBINATIONAL LETHALS IN THE X-CHROMOSOME OF DROSOPHILA
      MELANOGASTER.

PMID- 16589610
TI  - WAVES WITH Pn AND Sn VELOCITY AT GREAT DISTANCES.

PMID- 16589608
TI  - EXTRACTION OF COLLAGEN FROM CONNECTIVE TISSUE BY NEUTRAL SALT SOLUTIONS.

PMID- 16589611
TI  - ON THE ORIGIN OF TEKTITES.

PMID- 16589612
TI  - DYNAMIC PROGRAMMING AND A NEW FORMALISM IN THE THEORY OF INTEGRAL EQUATIONS.

PMID- 16589613
TI  - ARITHMETIC GENERA OF NORMAL VARIETIES IN AN ALGEBRAIC FAMILY.

PMID- 16589615
TI  - ON THE TRANSCENDENTAL MODULI OF ALGEBRAIC RIEMANN SURFACES.

PMID- 16589614
TI  - ON GENERATING FUNCTIONS FOR RESTRICTED PARTITIONS OF RATIONAL INTEGERS.

PMID- 16589616
TI  - ON MONOTONIC FUNCTIONS WHOSE SPECTRUM IS A CANTOR SET WITH CONSTANT RATIO OF
      DISSECTION.

PMID- 16589617
TI  - RADIOAUTOGRAPHIC STUDIES OF KERATIN FORMATION.

PMID- 16589618
TI  - THE CEPHALOCARIDA, A NEW SUBCLASS OF CRUSTACEA FROM LONG ISLAND SOUND.

PMID- 16589619
TI  - TOPOLOGICAL PROPERTIES OF COILED HELICAL SYSTEMS.

PMID- 16589620
TI  - THE ASSOCIATION OF IONS IN DIOXANE-WATER MIXTURES AT 25 degrees.

PMID- 16589621
TI  - BIOCHEMICAL CHARACTERISTICS OF ALDEHYDE AND LUCIFERASE MUTANTS OF LUMINOUS
      BACTERIA.

PMID- 16589622
TI  - INTERACTIONS AMONG VARIANT AND WILD-TYPE STRAINS OF CELLULAR SLIME MOLDS ACROSS
      THIN AGAR MEMBRANES.

PMID- 16589624
TI  - SPLITTING OF VALUATIONS IN EXTENSIONS OF LOCAL DOMAINS.

PMID- 16589623
TI  - STRUCTURAL AND FUNCTIONAL ASPECTS OF THE A COMPLEXES IN MAIZE. I. EVIDENCE FOR
      STRUCTURAL AND FUNCTIONAL VARIABILITY AMONG COMPLEXES OF DIFFERENT GEOGRAPHIC
      ORIGIN.

PMID- 16589625
TI  - INVARIANTS D'UNE APPLICATION CONTINUE.

PMID- 16589626
TI  - PROOF FOR AN ENDOGENOUS COMPONENT IN PERSISTENT SOLAR AND LUNAR RHYTHMICITY IN
      ORGANISMS.

PMID- 16589627
TI  - ISOELECTRIC SPECTRA AND MOBILITY SPECTRA: A NEW APPROACH TO ELECTROPHORETIC
      SEPARATION.

PMID- 16589628
TI  - A FURTHER STUDY OF THE APPARENT SYNTHESIS OF VITAMIN B(12) BY MAMMARY CANCERS OF
      MICE.

PMID- 16589630
TI  - INVESTIGATIONS ON LIGNIN AND LIGNIFICATION. XV. HETEROGENEITY OF NATIVE AND
      ENZYMATICALLY LIBERATED LIGNINS AS ESTABLISHED BY ELECTROPHORESIS AND PAPER
      CHROMATOGRAPHY.

PMID- 16589629
TI  - A GENERALIZED THEORY OF PLASTICITY INVOLVING THE VIRIAL THEOREM.

PMID- 16589631
TI  - THE COSMIC ABUNDANCES OF POTASSIUM, URANIUM, AND THORIUM AND THE HEAT BALANCES OF
      THE EARTH, THE MOON, AND MARS.

PMID- 16589632
TI  - SOLUTION OF A PROCESS OF RANDOM GENETIC DRIFT WITH A CONTINUOUS MODEL.

PMID- 16589633
TI  - AN X-RAY ANALYSIS OF CHROMOSOME DUPLICATION.

PMID- 16589634
TI  - BREAKAGE OF CHROMOSOMES IN Tradescantia WITH A CALCIUM DEFICIENCY.

PMID- 16589635
TI  - ON THE NICKEL, COBALT, AND COPPER CONTENTS OF DEEP-SEA SEDIMENTS.

PMID- 16589636
TI  - BOUNDS FOR THE RATIOS OF THE CO-ORDINATES OF THE CHARACTERISTIC VECTORS OF A
      MATRIX.

PMID- 16589637
TI  - AN EXTENSION OF THE MAXWELL THEORY.

PMID- 16589638
TI  - MULTIPLICITY THEORY FOR OPERATOR ALGEBRAS.

PMID- 16589639
TI  - ABELIAN VARIETIES OVER FINITE FIELDS.

PMID- 16589640
TI  - ON MODULI IN CONFORMAL MAPPING.

PMID- 16589641
TI  - POSSIBLE SEPARATION OF INTERTWINED NUCLEIC ACID CHAINS BY TRANSFER-TWIST.

PMID- 16589642
TI  - THE MAGELLANIC CLOUDS. XIV. THE BAR OF THE LARGE CLOUD.

PMID- 16589644
TI  - THE MODE OF GROWTH OF EPIDERMAL CELLS OF THE Avena Coleoptile.

PMID- 16589643
TI  - ACETYL-CHYMOTRYPSIN.

PMID- 16589645
TI  - THE CRYSTAL STRUCTURE AND TWINNING OF Co(2)S(3).

PMID- 16589646
TI  - THE STRUCTURE OF LIQUID HELIUM.

PMID- 16589647
TI  - MATERNAL AGING AND SOMATIC CROSSING OVER OF ATTACHED-X CHROMOSOMES.

PMID- 16589648
TI  - ABERRANT RECOMBINATION OF PYRIDOXINE MUTANTS OF Neurospora.

PMID- 16589649
TI  - SPLITTING OF VALUATIONS IN EXTENSIONS OF LOCAL DOMAIN II.

PMID- 16589650
TI  - ON THE EXISTENCE OF THE DERIVATIVE OF MARKOFF TRANSITION PROBABILITY FUNCTIONS.

PMID- 16589651
TI  - ON SOME NONLINEAR INTEGRAL EQUATIONS OCCURRING IN THE THEORY OF DYNAMIC
      PROGRAMMING.

PMID- 16589652
TI  - CONVERGENCE ALMOST EVERYWHERE OF OPERATOR AVERAGES.

PMID- 16589653
TI  - UNIFORMLY BOUNDED REPRESENTATIONS OF GROUPS.

PMID- 16589654
TI  - ON CANONICAL CONSTRUCTIONS. I.

PMID- 16589655
TI  - ON THE MODULI OF RIEMANN SURFACES.

PMID- 16589656
TI  - NONANALYTIC FUNCTIONS OF ABSOLUTELY CONVERGENT FOURIER SERIES.

PMID- 16589657
TI  - ON THE GENERATING PARAMETRIX OF THE STOCHASTIC PROCESSES.

PMID- 16589658
TI  - AN APPLICATION OF THE POISSON-BOLTZMANN EQUATION TO NONIDENTICAL, CHARGED
      PARTICLES.

PMID- 16589659
TI  - THE ENZYMATIC SYNTHESIS IN VITRO OF HYALURONIC ACID CHAINS.

PMID- 16589660
TI  - ELECTRON-MICROSCOPIC EVIDENCE FOR THE LOCALIZATION OF RIBONUCLEIC ACID IN THE
      PARTICLES OF TOBACCO MOSAIC VIRUS.

PMID- 16589661
TI  - NONVISUAL FUNCTIONING OF OCCIPITAL CORTEX IN THE MONKEY.

PMID- 16589662
TI  - DO FUCUS EGGS INTERACT THROUGH A CO(2)-pH GRADIENT?

PMID- 16589663
TI  - RESISTANCE AND SUSCEPTIBILITY OF CARROT ROOTS TO CROWN-GALL TUMOR FORMATION.

PMID- 16589664
TI  - CONDUCTANCE OF STRONG ELECTROLYTES AT FINITE DILUTIONS.

PMID- 16589665
TI  - AN INTERACTION BETWEEN ALLELES AT THE RH LOCUS IN MAN WHICH WEAKENS THE
      REACTIVITY OF THE RH(0) FACTOR (D).

PMID- 16589666
TI  - AN EXTREME CASE OF HETEROSIS IN A CENTRAL AMERICAN POPULATION OF DROSOPHILA
      TROPICALIS.

PMID- 16589667
TI  - THE EFFECT OF CHRONIC GAMMA RADIATION ON THE PRODUCTION OF SOMATIC MUTATIONS IN
      CARNATIONS.

PMID- 16589668
TI  - SPECULATIONS ON GENE ACTION AND PROTEIN SPECIFICITY.

PMID- 16589670
TI  - A CLOSURE PROBLEM RELATED TO THE RIEMANN ZETA-FUNCTION.

PMID- 16589669
TI  - INDUCED POLLEN LETHALS FROM SEEDS OF DATURA STRAMONIUM EXPOSED TO DIFFERENT
      RADIATIONS.

PMID- 16589671
TI  - INTEGRABLE AND SQUARE-INTEGRABLE REPRESENTATIONS OF A SEMISIMPLE LIE GROUP.

PMID- 16589672
TI  - A FUNDAMENTAL INEQUALITY IN THE THEORY OF PICARD VARIETIES.

PMID- 16589673
TI  - A PATH SPACE AND THE STIEFEL-WHITNEY CLASSES.

PMID- 16589674
TI  - CHANGES IN THE NUCLEI OF DIFFERENTIATING GASTRULA CELLS, AS DEMONSTRATED BY
      NUCLEAR TRANSPLANTATION.

PMID- 16589675
TI  - ZINC, A COMPONENT OF YEAST ALCOHOL DEHYDROGENASE.

PMID- 16589676
TI  - PRODUCTION OF ABNORMAL (PSYCHOTIC?) BEHAVIOR IN MICE WITH LYSERGIC ACID
      DIETHYLAMIDE, AND ITS PARTIAL PREVENTION WITH CHOLINERGIC DRUGS AND SEROTONIN.

PMID- 16589677
TI  - FINE STRUCTURE OF A GENETIC REGION IN BACTERIOPHAGE.

PMID- 16589678
TI  - CHROMOSOMAL ABERRATIONS IN DATURA DUE TO VARIOUS KINDS OF IRRADIATION.

PMID- 16589679
TI  - EVIDENCE OF COMPLEX LOCI IN SALMONELLA.

PMID- 16589680
TI  - GENETICALLY CONDITIONED METABOLIC ANTAGONISM AND SUPPRESSOR ACTION IN Neurospora.

PMID- 16589681
TI  - NUCLEO-CYTOPLASMIC RELATIONS IN SALIVARY-GLAND CELLS OF Drosophila.

PMID- 16589682
TI  - PHENOTYPIC VARIATION AND PSEUDO-ALLELISM AT THE FORKED LOCUS IN Drosophila
      Melanogaster.

PMID- 16589683
TI  - CURVILINEAR CLUSTER SETS OF ARBITRARY FUNCTIONS.

PMID- 16589684
TI  - ON A CHARACTERIZATION OF THE NORMAL LAW.

PMID- 16589685
TI  - ON THE ADDITIVITY OF THE TRACE IN FINITE FACTORS.

PMID- 16589686
TI  - REPRESENTATION OF A CLASS OF STOCHASTIC Processes.

PMID- 16589687
TI  - A VARIATIONAL METHOD IN THE THEORY OF HARMONIC INTEGRALS.

PMID- 16589688
TI  - ON THE CHARACTERS OF THE SYMMETRIC GROUP.

PMID- 16589689
TI  - CLUSTER SETS OF FUNCTIONS MEROMORPHIC IN THE UNIT CIRCLE.

PMID- 16589690
TI  - INTERACTIONS BETWEEN ELECTRONS AND WAVES.

PMID- 16589691
TI  - NOTE ON THE SIMPLE COLLISION THEORY OF BIMOLECULAR REACTIONS.

PMID- 16589692
TI  - A THEORY CONCERNING THE MECHANISM OF ALLERGIC DISEASES.

PMID- 16589693
TI  - SOME CRITICISMS OF "ON THE ORIGIN OF THE LUNAR SURFACE FEATURES" BY G. P. KUIPER.

PMID- 16589694
TI  - EFFECT OF ADENINE MONONUCLEOTIDES ON NEURAL TUBE FORMATION OF FROG EMBRYO.

PMID- 16589695
TI  - A RAPID METHOD FOR VIABLE CELL TITRATION AND CLONE PRODUCTION WITH HELA CELLS IN
      TISSUE CULTURE: THE USE OF X-IRRADIATED CELLS TO SUPPLY CONDITIONING FACTORS.

PMID- 16589696
TI  - HINDERED CIS ISOMERS OF VITAMIN A AND RETINENE: THE STRUCTURE OF THE NEO-B
      ISOMER.

PMID- 16589697
TI  - ISOTOPE SEPARATION BY IONIC EXPANSION IN A MAGNETIC FIELD.

PMID- 16589698
TI  - GRAVITY ANOMALIES AT CONTINENTAL MARGINS.

PMID- 16589699
TI  - THE SEISMIC SURFACE PULSE.

PMID- 16589700
TI  - ON INVOLUTORIAL ALGEBRAS.

PMID- 16589702
TI  - STATIONARY SPACE-TIME IN GENERAL RELATIVITY.

PMID- 16589701
TI  - FUNCTIONAL EQUATIONS IN THE THEORY OF DYNAMIC PROGRAMMING. II. NONLINEAR
      DIFFERENTIAL EQUATIONS.

PMID- 16589703
TI  - THE COHOMOLOGY RING OF G/T.

PMID- 16589704
TI  - GEOMETRIC ASPECTS OF CURRENTS AND DISTRIBUTIONS.

PMID- 16589706
TI  - DIGITAL COMPUTATIONAL METHODS IN SYMBOLIC LOGIC, WITH EXAMPLES IN BIOCHEMISTRY.

PMID- 16589705
TI  - GENERAL FACTORS OF AUTOMORPHY.

PMID- 16589707
TI  - THE BEHAVIOR OF A COMPLEX FUNCTION AT INFINITY.

PMID- 16589708
TI  - ON THE GENERATION OF THE IRREDUCIBLE REPRESENTATIONS OF THE SYMMETRIC GROUP.

PMID- 16589709
TI  - ON THE ANALYSIS OF THE KRONECKER PRODUCT OF IRREDUCIBLE REPRESENTATIONS OF S(n).

PMID- 16589710
TI  - AN APPLICATION OF ALGEBRAIC TOPOLOGY TO NUMERICAL ANALYSIS: ON THE EXISTENCE OF A
      SOLUTION TO THE NETWORK PROBLEM.

PMID- 16589711
TI  - THE ROLES OF THE OPTIC VESICLE AND OTHER HEAD TISSUES IN LENS INDUCTION.

PMID- 16589712
TI  - NATIONAL ACADEMY OF SCIENCES: July 1, 1955.

PMID- 16589713
TI  - PATHWAY OF SERINE FORMATION FROM CARBOHYDRATE IN RAT LIVER.

PMID- 16589714
TI  - DERIVATIVES OF MENADIONE AS ELECTRON ACCEPTORS IN THE OXIDATION OF REDUCED
      DIPHOSPHOPYRIDINE NUCLEOTIDE.

PMID- 16589715
TI  - METABOLIC PECULIARITIES IN NORMAL YOUNG MEN AS REVEALED BY REPEATED BLOOD
      ANALYSES.

PMID- 16589716
TI  - NYBOMYCIN, A NEW ANTIBIOTIC WITH ANTIPHAGE AND ANTIBACTERIAL PROPERTIES.

PMID- 16589717
TI  - THE SYNERGISM BETWEEN ULTRAVIOLET LIGHT AND TERTIARYBUTYL HYDROPEROXIDE IN THEIR
      MUTAGENIC EFFECTIVENESS IN DROSOPHILA.

PMID- 16589718
TI  - THE SEISMIC BURIED PULSE.

PMID- 16589719
TI  - ON HERMITIAN OPERATORS OVER THE CAYLEY ALGEBRA.

PMID- 16589720
TI  - RELATIONS BETWEEN THE COHOMOLOGY GROUPS OF DOLBEAULT AND TOPOLOGICAL INVARIANTS.

PMID- 16589721
TI  - THE INTEGRAL OF THE ASSOCIATED LEGENDRE FUNCTION.

PMID- 16589722
TI  - SIMPLE SUBVARIETIES OF ANALYTIC VARIETIES.

PMID- 16589723
TI  - ON THE PROPERTIES OF CERTAIN TRINOMIAL EQUATIONS IN A FINITE FIELD.

PMID- 16589724
TI  - REDISTRIBUTION OF CLASSICAL AND QUANTUM DENSITIES.

PMID- 16589725
TI  - SOLUTION OF THE BOLTZMANN-HILBERT INTEGRAL EQUATION.

PMID- 16589727
TI  - SOCIAL BEHAVIOR IN FRESH-WATER FISH AND ITS EFFECT ON RESISTANCE TO TRYPANOSOMES.

PMID- 16589726
TI  - EXPERIMENTAL REVERSAL OF SEX IN THE GON ADS OF THE OPOSSUM DIDELPHIS VIRGINIANA.

PMID- 16589728
TI  - ECTOPIC DIFFERENTIATION OF EARS IN SECONDARY EMBRYOS OF FUNDULUS.

PMID- 16589729
TI  - THE MAGELLANIC CLOUDS. XV. ON THE TILT OF THE LARGE CLOUD.

PMID- 16589730
TI  - RECONSTITUTION OF ACTIVE TOBACCO MOSAIC VIRUS FROM ITS INACTIVE PROTEIN AND
      NUCLEIC ACID COMPONENTS.

PMID- 16589731
TI  - ENZYME FORMATION IN PROTOPLASTS OF BACILLUS MEGATERIUM.

PMID- 16589732
TI  - THE DISTRIBUTION OF PARENTAL PHOSPHORUS ATOMS AMONG BACTERIOPHAGE PROGENY.

PMID- 16589733
TI  - STUDIES OF MOLECULAR INTERACTION IN ISOIONIC PROTEIN SOLUTIONS BY LIGHT
      SCATTERING.

PMID- 16589734
TI  - A NOTE ON THE ORIGIN OF LIFE.

PMID- 16589735
TI  - ON THE STRUCTURE OF THE STRESS-STRAIN RELATIONS.

PMID- 16589736
TI  - COMBINED ELASTIC AND PRANDTL-REUSS STRESS-STRAIN RELATIONS.

PMID- 16589737
TI  - CHROMOSOME STRUCTURE AND THE MECHANISM OF CROSSING OVER.

PMID- 16589739
TI  - REGULAR FUNCTIONS WITH PRESCRIBED MEASURABLE BOUNDARY VALUES ALMOST EVERYWHERE.

PMID- 16589738
TI  - THE GULF STREAM AS AN INERTIAL BOUNDARY LAYER.

PMID- 16589740
TI  - FUNCTIONAL EQUATIONS IN THE THEORY OF DYNAMIC PROGRAMMING. V. POSITIVITY AND
      QUASI-LINEARITY.

PMID- 16589741
TI  - EXISTENCE OF FUNCTIONALLY INDEPENDENT AUTOMORPHIC FUNCTIONS.

PMID- 16589742
TI  - SOME SPECIAL EQUATIONS IN A FINITE FIELD.

PMID- 16589743
TI  - THE LOCAL STRUCTURE OF THE ARTIN ROOT NUMBER.

PMID- 16589745
TI  - DEGENERATE SCALAR INVARIANTS AND THE GROUPS OF MOTION OF A RIEMANN SPACE.

PMID- 16589744
TI  - THE DIVISION PROBLEM FOR DISTRIBUTIONS.

PMID- 16589746
TI  - KINEMATICALLY PREFERRED CO-ORDINATE SYSTEMS.

PMID- 16589747
TI  - RELATION OF THE THEORY OF CERTAIN TRINOMIAL EQUATIONS IN A FINITE FIELD TO
      FERMAT'S LAST THEOREM.

PMID- 16589748
TI  - ON CYCLOTOMIC RELATIONS AND TRINOMIAL EQUATIONS IN A FINITE FIELD.

PMID- 16589749
TI  - ON THE DIVISORS OF THE SECOND FACTOR OF THE CLASS NUMBER OF A CYCLOTOMIC FIELD.

PMID- 16589750
TI  - INHERITANCE AND REGENERATION OF CYTOPLASMIC DAMAGE IN Paramecium Aurelia.

PMID- 16589751
TI  - DIFFERENTIATION IN CULTURE OF MIXED AGGREGATES OF DISSOCIATED TISSUE CELLS.

PMID- 16589753
TI  - APPLICATION OF STATISTICAL METHODS IN WEATHER PREDICTION.

PMID- 16589752
TI  - PHOTOREACTIVATION EXPERIMENTS ON THE NUCLEUS AND CYTOPLASM OF THE Habrobracon
      EGG.

PMID- 16589754
TI  - THE LUNAR SURFACE-FURTHER COMMENTS.

PMID- 16589755
TI  - THE MAGELLANIC CLOUDS. XVI. INFRARED STARS AND STELLAR EVOLUTION.

PMID- 16589756
TI  - MAGELLANIC CLOUDS. XVII. SEVEN NOTES ON THE CEPHEID VARIABLES.

PMID- 16589757
TI  - GALACTIC AND EXTRAGALACTIC STUDIES, XXIII. OPACITY OF THE SOUTHERN MILKY WAY DUST
      CLOUDS.

PMID- 16589758
TI  - ENZYME LOCALIZATION IN Azotobacter Vinelandii.

PMID- 16589760
TI  - THE INFLUENCE OF PLOIDY AND DIVISION STAGE ON THE ANOXIC PROTECTION OF
      Saccharomyces Cerevisiae AGAINST X-RAY INACTIVATION.

PMID- 16589759
TI  - THE NATURAL-SELECTION THEORY OF ANTIBODY FORMATION.

PMID- 16589761
TI  - TRYPTOPHAN BIOSYNTHESIS IN Salmonella Typhimurium.

PMID- 16589762
TI  - AMINO ACID ADSORPTION AND PROTEIN SYNTHESIS IN Escherichia Coli.

PMID- 16589763
TI  - VIRULENT-AVIRULENT CONVERSIONS OF Rickettsia Rickettsii IN VITRO.

PMID- 16589764
TI  - DIRECT EVIDENCE FOR NUCLEAR SYNTHESIS OF CYTOPLASMIC RIBOSE NUCLEIC ACID.

PMID- 16589765
TI  - THE ENZYMATIC ACTIVATION OF SULFATE.

PMID- 16589766
TI  - THE ROLE OF PURINE BASES AS HISTIDINE PRECURSORS IN Lactobacillus Casei.

PMID- 16589767
TI  - OVERNIGHT NUTRITIONAL RESPONSES OF CHICKS.

PMID- 16589768
TI  - IRREVERSIBLE THERMODYNAMICS AND RATE THEORY.

PMID- 16589769
TI  - COMBINED ELASTIC AND VON MISES STRESS-STRAIN RELATIONS.

PMID- 16589770
TI  - INTERCHROMOSOMAL EFFECTS AND SEGREGATION.

PMID- 16589771
TI  - FREQUENCIES OF INVERSION COMBINATIONS IN THE THIRD CHROMOSOME OF WILD MALES OF
      Drosophila Pseudoobscura.

PMID- 16589772
TI  - FUNCTIONAL AND SPATIAL PSEUDOALLELISM AT THE SINGED LOCUS IN Drosophila.

PMID- 16589773
TI  - A MODEL FOR INTRACELLULAR TRANSFER OF DNA (GENE) SPECIFICITY.

PMID- 16589774
TI  - FURTHER EVIDENCE OF ABERRANT RECOMBINATION IN Neurospora.

PMID- 16589775
TI  - A DISCREPANCY BETWEEN CALCULATION AND MEASUREMENT OF SUBMARINE ILLUMINATION.

PMID- 16589776
TI  - A CLASS OF ARITHMETICAL FUNCTIONS.

PMID- 16589777
TI  - COMPLETELY INVERSIBLE OPERATORS.

PMID- 16589778
TI  - FULLY CONVEX NORMED LINEAR SPACES.

PMID- 16589779
TI  - NOTE ON THE DEFINITE INTEGRAL OVER PRODUCTS OF THREE LEGENDRE FUNCTIONS.

PMID- 16589780
TI  - ON THE CONCEPT OF FIBER SPACE.

PMID- 16589781
TI  - ON THE SPECTRAL SEQUENCE OF A FIBER SPACE.

PMID- 16589782
TI  - ON SOME PROBLEMS IN ABSTRACT ALGEBRAIC GEOMETRY.

PMID- 16589783
TI  - ON THE CONJUGACY OF REAL CARTAN SUBALGEBRAS. I.

PMID- 16589784
TI  - PROOF OF FERMAT'S LAST THEOREM FOR ALL PRIME EXPONENTS LESS THAN 4002.

PMID- 16589785
TI  - RELATIVE QUASI-COMPACTNESS OF MAPPINGS.

PMID- 16589786
TI  - CHRONOLOGIC ASSOCIATION OF POLIOMYELITIS AND COXSACKIE VIRUS INFECTIONS.

PMID- 16589787
TI  - MICROWAVE SPECTROSCOPY OF BIOLOGICAL SUBSTANCES. I. PARAMAGNETIC RESONANCE IN X
      IRRADIATED AMINO ACIDS AND PROTEINS.

PMID- 16589788
TI  - MICROWAVE SPECTROSCOPY OF BIOLOGICAL SUBSTANCES. II. PARAMAGNETIC RESONANCE IN X
      IRRADIATED CARBOXYLIC AND HYDROXY ACIDS.

PMID- 16589789
TI  - STATISTICAL CORRELATION OF PROTEIN AND RIBONUCLEIC ACID COMPOSITION.

PMID- 16589790
TI  - CRYSTALLIZATION OF PURIFIED MEF-1 POLIOMYELITIS VIRUS PARTICLES.

PMID- 16589791
TI  - INFLUENCE OF AUXIN ON CELL-WALL METABOLISM.

PMID- 16589792
TI  - THE PERMEABILITY OF POTATO TISSUE TO WATER.

PMID- 16589793
TI  - THE ION-PAIR EQUILIBRIUM OF ELECTROLYTE SOLUTIONS IN DIOXANE-WATER MIXTURES.

PMID- 16589794
TI  - ON THE CHEMICAL STRUCTURE OF THE REACTIVE SITES OF ANTIBODY MOLECULES.

PMID- 16589795
TI  - RADIATION DAMAGE IN THE DEVELOPING GERM CELLS OF Drosophila Virilis.

PMID- 16589796
TI  - A POSSIBLE MECHANISM FOR THE REPLICATION OF THE HELICAL STRUCTURE OF
      DESOXYRIBONUCLEIC ACID.

PMID- 16589797
TI  - SUPPRESSIVENESS: A NEW FACTOR IN THE GENETIC DETERMINISM OF THE SYNTHESIS OF
      RESPIRATORY ENZYMES IN YEAST.

PMID- 16589798
TI  - A CYTOGENETIC STUDY OF THE X CHROMOSOME OF Drosophila Busckii AND ITS RELATION TO
      PHYLOGENY.

PMID- 16589799
TI  - Dystrophia Muscularis: A HEREDITARY PRIMARY MYOPATHY IN THE HOUSE MOUSE.

PMID- 16589800
TI  - RECOMBINATION INCREASE DUE TO HETEROLOGOUS INVERSIONS AND THE RELATION TO
      CYTOLOGICAL LENGTH.

PMID- 16589801
TI  - ABSTRACT HOMOTOPY.

PMID- 16589802
TI  - ON THE IRREDUCIBLE REPRESENTATIONS OF THE SYMMETRIC GROUP.

PMID- 16589803
TI  - UNIQUENESS OF THE FINE-STRUCTURE CONSTANT.

PMID- 16589804
TI  - ON FORCE-FREE MAGNETIC FIELDS.

PMID- 16589805
TI  - CHANGES IN THE COMPOSITION OF AN ACTINOMYCIN COMPLEX DURING GROWTH OF A
      STREPTOMYCES CULTURE.

PMID- 16589806
TI  - ON THE MECHANISM OF HYDROGENASE ACTION.

PMID- 16589807
TI  - PIGMENT CONVERSION IN THE FORMATIVE RESPONSES OF PLANTS TO RADIATION.

PMID- 16589808
TI  - PROGRESSIVE CONFIGURATIONAL CHANGES, DURING CELL DIVISION, OF CELLS WITHIN THE
      APICAL MERISTEM.

PMID- 16589810
TI  - HOMOLOGICAL DIMENSION IN NOETHERIAN RINGS.

PMID- 16589809
TI  - THE OPTICAL ROTATORY POWER OF HELICAL MOLECULES.

PMID- 16589811
TI  - GENERAL THEORY OF ELLIPTIC EQUATIONS.

PMID- 16589812
TI  - SPECTRAL SYNTHESIS FOR THE CANTOR SET.

PMID- 16589813
TI  - A CENTRAL LIMIT THEOREM AND A STRONG MIXING CONDITION.

PMID- 16589814
TI  - THE EQUILIBRIUM OF MAGNETIC STARS.

PMID- 16589815
TI  - GALACTOSEMIA, A CONGENITAL DEFECT IN A NUCLEOTIDE TRANSFERASE: A PRELIMINARY
      REPORT.

PMID- 16589816
TI  - THE COMBINING POWER OF MYOGLOBIN FOR ALKYL ISOCYANIDES AND THE STRUCTURE OF THE
      MYOGLOBIN MOLECULE.

PMID- 16589817
TI  - THE CONTROL OF A CANCER GROWTH IN EMBRYONATED EGGS.

PMID- 16589818
TI  - HYDROGEN-BONDED HELICAL CONFIGURATIONS OF POLYNUCLEOTIDES.

PMID- 16589819
TI  - PHASE RELATIONS IN SYSTEMS COMPRISING BROMINE AND QUATERNARY AND TERNARY ALKYL
      AMMONIUM BROMIDES OR CHLORIDES.

PMID- 16589820
TI  - CHEMICAL ALTERATION OF CROSSING-OVER FREQUENCY IN CHLAMYDOMONAS.

PMID- 16589821
TI  - A FURTHER ANALYSIS OF THE FORKED LOCUS IN DROSOPHILA MELANOGASTER.

PMID- 16589822
TI  - THE EFFECTS OF THERMAL-NEUTRON RADIATION ON MUTATION OF ENDOSPERM LOCI IN MAIZE.

PMID- 16589823
TI  - THE THERMAL CLASSIFICATION OF LAKES.

PMID- 16589824
TI  - GAMMA FACTORS IN FUNCTIONAL EQUATIONS.

PMID- 16589825
TI  - THE REPRESENTATION OF A C-BIMEASURE ON A GENERAL RECTANGLE.

PMID- 16589826
TI  - ON THE KRONECKER PRODUCT OF IRREDUCIBLE REPRESENTATIONS OF THE SYMMETRIC GROUP.

PMID- 16589827
TI  - ON GENERALIZED TCHEBYCHEFF POLYNOMIALS.

PMID- 16589828
TI  - ON COWLING'S THEOREM ON THE IMPOSSIBILITY OF SELF-MAINTAINED AXISYMMETRIC
      HOMOGENEOUS DYNAMOS.

PMID- 16589829
TI  - EQUATIONS TO OBTAIN, FOR EQUILIBRIUM REACTIONS, FREE-ENERGY, HEAT, AND ENTROPY
      CHANGES FROM TWO CALORIMETRIC MEASUREMENTS.

PMID- 16589830
TI  - THE ARRANGEMENT OF ATOMS IN CRYSTALS OF THE WOLLASTONITE GROUP OF METASILICATES.

PMID- 16589831
TI  - ALGEBRAIC VARIETIES WITH RATIONAL DISSECTIONS.

PMID- 16589832
TI  - BINARY CONGRUENCES IN ALGEBRAIC NUMBER FIELDS.

PMID- 16589833
TI  - COMBINATORIAL PROBLEMS IN THE THEORY OF GRAPHS. I.

PMID- 16589834
TI  - NOTE ON PROJECTIVELY EUCLIDEAN HERMITIAN MANIFOLDS.

PMID- 16589836
TI  - PROOF OF AN IDENTITY ON JORDAN ALGEBRAS.

PMID- 16589835
TI  - PREDICATES, TERMS, OPERATIONS, AND EQUALITY IN POLYADIC BOOLEAN ALGEBRAS.

PMID- 16589837
TI  - A THEOREM ON THE STRUCTURE OF JORDAN ALGEBRAS.

PMID- 16589838
TI  - ON INVARIANT SKEW-TENSORS.

PMID- 16589839
TI  - REMARK ON KINEMATICALLY PREFERRED CO-ORDINATE SYSTEMS.

PMID- 16589840
TI  - ON CONSISTENT ESTIMATES OF THE SPECTRAL DENSITY OF A STATIONARY TIME SERIES.

PMID- 16589841
TI  - ON WEYL'S IMBEDDING PROBLEM.

PMID- 16589842
TI  - THE BEHAVIOR IN TRANSPLANT OF LYMPHOCYTIC NEOPLASMS ARISING FROM PARENTAL THYMIC
      GRAFTS IN IRRADIATED, THYMECTOMIZED HYBRID MICE.

PMID- 16589843
TI  - PISCIVOROUS GASTROPODS OF THE GENUS CONUS.

PMID- 16589844
TI  - ELEMENT-BUILDING REACTIONS IN STARS.

PMID- 16589846
TI  - GROWTH RESPONSE OF SINGLE-GENE DWARF MUTANTS IN MAIZE TO GIBBERELLIC ACID.

PMID- 16589845
TI  - A COMPARISON OF THE HYDROGENASE ACTIVITIES OF DIFFERENT MICROORGANISMS.

PMID- 16589847
TI  - THE q LOCUS OF NEUROSPORA CRASSA.

PMID- 16589849
TI  - ON COVERING A CIRCLE BY RANDOMLY PLACED ARCS.

PMID- 16589848
TI  - A CASE OF POLYPLOIDY IN DIPTERA.

PMID- 16589850
TI  - COMBINATORIAL PROBLEMS IN THE THEORY OF GRAPHS. II.

PMID- 16589851
TI  - ON THE LITTLEWOOD-PALEY FUNCTION g (theta).

PMID- 16589852
TI  - THE SENSITIVITY OF THE TURTLE'S EAR AS SHOWN BY ITS ELECTRICAL POTENTIALS.

PMID- 16589853
TI  - ON THE MECHANISM AND OPTICAL SPECIFICITY OF TRANSAMINATION REACTIONS.

PMID- 16589855
TI  - MICROWAVE ABSORPTION AND MOLECULAR STRUCTURE IN LIQUIDS. XVII. DIELECTRIC
      RELAXATION TIMES AND SHAPES OF RIGID MOLECULES.

PMID- 16589854
TI  - THE DISTRIBUTION OF POLIO ANTIBODIES IN SERUM PROTEINS.

PMID- 16589856
TI  - THE MUTATION OF LINKED MAIZE ENDOSPERM LOCI INDUCED BY THERMAL-NEUTRON, X-,
      GAMMA, AND ULTRAVIOLET RADIATION.

PMID- 16589857
TI  - A BINARY MUTABILITY SYSTEM IN ESCHERICHIA COLI.

PMID- 16589858
TI  - A UNIFIED THEORY OF GENERAL RELATIVITY OF GRAVITATION AND ELECTROMAGNETISM.

PMID- 16589859
TI  - INVARIANT DIFFERENTIAL OPERATORS ON A SEMISIMPLE LIE ALGEBRA.

PMID- 16589860
TI  - HARMONIC ANALYSIS FOR CERTAIN SEMIGROUPS.

PMID- 16589861
TI  - ABSTRACT HOMOTOPY. II.

PMID- 16589863
TI  - IMPLICIT FUNCTION THEOREM FOR QUASI-ANALYTIC AND RELATED CLASSES OF FUNCTIONS.

PMID- 16589862
TI  - ON DIFFERENTIAL GEOMETRY AND HOMOGENEOUS SPACES. I.

PMID- 16589865
TI  - A GENERALIZATION OF THE PONTRJAGIN SQUARE COHOMOLOGY OPERATION.

PMID- 16589864
TI  - ON DIOPHANTINE EQUATIONS WHICH HAVE NO SOLUTIONS.

PMID- 16589867
TI  - ON THE STABILITY OF THE SIMPLEST SOLUTION OF THE EQUATIONS OF HYDROMAGNETICS.

PMID- 16589866
TI  - COURSE OF PRODUCTION OF AN ISOANTISERUM EFFECTING TUMOR HOMOGRAFT SURVIVAL IN
      MICE.

PMID- 16589868
TI  - WAVES IN A LATTICE OF SPHERICAL SCATTERERS.

PMID- 16589869
TI  - DETERMINATION OF CRYSTAL STRUCTURES BY MEANS OF ANOMALOUSLY SCATTERED X-RAYS.

PMID- 16589870
TI  - SOUND TRANSMISSION IN THE TURTLE'S EAR.

PMID- 16589871
TI  - NEW EXPERIMENTS ON CHEMICAL PHENOCOPIES.

PMID- 16589872
TI  - ANTISERA THAT BLOCK CELL DIVISION IN DEVELOPING EGGS OF SEA URCHINS.

PMID- 16589873
TI  - INHIBITION OF DIVISION AND DEVELOPMENT OF SEA-URCHIN EGGS BY ANTISERA AGAINST
      FERTILIZIN.

PMID- 16589874
TI  - NEUTRALIZATION OF BACTERIOPHAGE BY THE PROPERDIN SYSTEM.

PMID- 16589875
TI  - THE MECHANISM OF DNA REPLICATION AND GENETIC RECOMBINATION IN PHAGE.

PMID- 16589876
TI  - THE PHYTOENE CONTENT OF TOMATOES.

PMID- 16589877
TI  - ON THE COBAR CONSTRUCTION.

PMID- 16589878
TI  - A CLASS OF STATIONARY PROCESSES AND A CENTRAL LIMIT THEOREM.

PMID- 16589879
TI  - MARKOFF PROCESSES AND POTENTIALS.

PMID- 16589880
TI  - ABSTRACT HOMOTOPY. III.

PMID- 16589882
TI  - A TOPOLOGICAL PROOF OF A THEOREM OF COMPLEX ANALYSIS.

PMID- 16589881
TI  - L-SERIES OF A COVERING.

PMID- 16589883
TI  - DISTRIBUTION FUNCTIONS OF ADDITIVE ARITHMETIC FUNCTIONS.

PMID- 16589884
TI  - THE REES-SUSCHKEWITSCH STRUCTURE THEOREM FOR COMPACT SIMPLE SEMIGROUPS.

PMID- 16589885
TI  - THE CHARACTERISTIC CLASSES OF AN ALGEBRAIC FIBER BUNDLE. I.

PMID- 16589886
TI  - ON THE UNWINDING OF DNA.

PMID- 16589887
TI  - SOLUTION OF AN INTEGRAL EQUATION OCCURRING IN IMPULSIVE WAVE PROPAGATION
      PROBLEMS.

PMID- 16589888
TI  - NATIONAL ACADEMY OF SCIENCES: July 1, 1956.

PMID- 16589889
TI  - PHOSPHORYLATIVE AND NONPHOSPHORYLATIVE PATHWAYS OF ELECTRON TRANSFER IN RAT LIVER
      MITOCHONDRIA.

PMID- 16589890
TI  - CONDUCTANCE, VISCOSITY, AND VAPOR DENSITY FOR SEVERAL SALTS IN BROMINE AT 25
      degrees.

PMID- 16589891
TI  - STUDIES OF TYROSINASE PRODUCTION BY A HETEROCARYON OF NEUROSPORA.

PMID- 16589892
TI  - THE GLUCOSE CONTENT OF THE DEOXYRIBONUCLEIC ACIDS OF CERTAIN BACTERIOPHAGES.

PMID- 16589893
TI  - PROPERTIES OF BACTERIOPHAGES T2 AND T4 WITH UNUSUAL INHERITANCE.

PMID- 16589894
TI  - THE PRODUCTION OF TWO CHEMICALLY DIFFERENT TYPES OF CHROMOSOMAL BREAKS BY
      IONIZING RADIATIONS.

PMID- 16589895
TI  - FREQUENCY OF SOMATIC MUTATION TO SELF COLOR IN MAIZE PLANTS HOMOZYGOUS AND
      HETEROZYGOUS FOR VARIEGATED PERICARP.

PMID- 16589896
TI  - ON MAUTNER'S EIGENFUNCTION EXPANSION.

PMID- 16589899
TI  - COMPATIBLE SEMINORMS IN A VECTOR LATTICE.

PMID- 16589898
TI  - COMBINATORIAL PROBLEMS IN THE THEORY OF GRAPHS. III.

PMID- 16589897
TI  - ON THE DISTRIBUTION OF CERTAIN FUNCTIONALS OF MARKOFF CHAINS AND PROCESSES.

PMID- 16589901
TI  - ANALYTIC GROUPS OVER COMPLETE FIELDS.

PMID- 16589900
TI  - A FORMULA FOR SEMISIMPLE LIE GROUPS.

PMID- 16589902
TI  - ABSTRACT HOMOTOPY. IV.

PMID- 16589903
TI  - FOUNDATIONS OF QUASIGROUPS.

PMID- 16589905
TI  - ON THE APPROACH TO THE FINAL PERIOD OF DECAY IN ISOTROPIC TURBULENCE ACCORDING TO
      HEISENBERG'S TRANSFER THEORY.

PMID- 16589904
TI  - SOME MOLECULAR COLLISION INTEGRALS FOR POINT ATTRACTION AND REPULSION POTENTIALS.

PMID- 16589906
TI  - ON THE CLASSIFICATION OF REINFORCEMENT SCHEDULES.

PMID- 16589907
TI  - A NERVE GROWTH-STIMULATING FACTOR ISOLATED FROM SNAKE VENOM.

PMID- 16589908
TI  - BACTERIAL PROTOPLASTS INDUCED BY PENICILLIN.

PMID- 16589909
TI  - HINDERED CIS ISOMERS OF VITAMIN A AND RETINENE: THE STRUCTURE OF THE NEO-b
      ISOMER.

PMID- 16589910
TI  - ON THE SYNTHESIS OF ANTIBODY PROTEIN IN VITRO.

PMID- 16589911
TI  - PRODUCTION OF PROTOPLASTS OF ESCHERICHIA COLI BY LYSOZYME TREATMENT.

PMID- 16589912
TI  - ION ASSOCIATION IN AQUEOUS SOLUTIONS OF 1-1 ELECTROLYTES AT 25 degrees.

PMID- 16589913
TI  - THE OPTICAL ROTATORY DISPERSION OF SIMPLE POLYPEPTIDES. I.

PMID- 16589914
TI  - ISOTROPIC MATERIALS WHOSE DEFORMATION AND DISTORTION ENERGIES ARE EXPRESSIBLE BY
      SCALAR INVARIANTS.

PMID- 16589915
TI  - CYTOLOGICAL DEMONSTRATION OF THE HELICAL STRUCTURE OF GIANT CHROMOSOMES.

PMID- 16589916
TI  - HETEROCARYOSIS AND PROTOPLASMIC INCOMPATIBILITY IN NEUROSPORA CRASSA.

PMID- 16589917
TI  - THE ORIENTATION AND EXTENT OF GENE TRANSFER IN ESCHERICHIA COLI.

PMID- 16589918
TI  - A PROPERTY OF SPECIAL JORDAN ALGEBRAS.

PMID- 16589919
TI  - ON A CLASS OF FUNCTIONAL EQUATIONS OF MODULAR TYPE.

PMID- 16589920
TI  - ON THE PRINCIPLE OF INVARIANT IMBEDDING AND PROPAGATION THROUGH INHOMOGENEOUS
      MEDIA.

PMID- 16589921
TI  - ON MULTIPLICATIVE IDEMPOTENTS OF A POTENT SEMIRING.

PMID- 16589923
TI  - CAUCHY'S PROBLEM FOR LINEAR DIFFERENTIAL EQUATIONS WITH CONSTANT COEFFICIENTS.

PMID- 16589922
TI  - GENERALIZED RESOLUTIONS OF THE IDENTITY FOR CLOSED SYMMETRIC ORDINARY
      DIFFERENTIAL OPERATORS.

PMID- 16589924
TI  - A UNIFIED THEORY OF GENERAL RELATIVITY OF GRAVITATION AND ELECTROMAGNETISM. II.

PMID- 16589925
TI  - SINGULAR INTEGRAL EQUATIONS FOR DIFFERENTIAL FORMS ON RIEMANNIAN MANIFOLDS.

PMID- 16589926
TI  - MEASURES OF THE VALUE OF INFORMATION.

PMID- 16589928
TI  - A FUNDAMENTAL THEORY OF SUPERCONDUCTIVITY.

PMID- 16589927
TI  - DIOPHANTINE EQUATIONS IN CERTAIN RINGS.

PMID- 16589929
TI  - CONVERGENT APPROACH TO THE THEORY OF ELEMENTARY PARTICLE INTERACTIONS.

PMID- 16589930
TI  - TEMPERATURE INDEPENDENCE IN A UNICELLULAR "CLOCK".

PMID- 16589931
TI  - INFLUENCE OF PROTEIN AND CALCIUM ADDITIONS TO ALREADY ADEQUATE DIET.

PMID- 16589932
TI  - MEASUREMENT OF IMPOSED VOLTAGE GRADIENT ADEQUATE TO MODULATE NEURONAL FIRING.

PMID- 16589933
TI  - IN VITRO AND IN VIVO EFFECTS OF A NERVE GROWTH-STIMULATING AGENT ISOLATED FROM
      SNAKE VENOM.

PMID- 16589934
TI  - ON TIME LAGS IN EQUATIONS OF GROWTH.

PMID- 16589935
TI  - OBSERVATIONS ON THE STRUCTURE OF DEOXYRIBONUCLEOPROTEIN GELS.

PMID- 16589936
TI  - THE EFFECT OF LIPOIC ACID ON RECOVERY IN INDUCED LYSOGENIC ORGANISMS.

PMID- 16589937
TI  - LIGHT-INDUCED PARAMAGNETISM IN CHLOROPLASTS.

PMID- 16589938
TI  - THE MECHANISM OF CHYMOTRYPSIN-CATALYZED REACTIONS.

PMID- 16589939
TI  - STUDIES ON SIALIC ACID OF SUBMAXILLARY MUCOID.

PMID- 16589940
TI  - AN IDENTICAL DUPLEX STRUCTURE FOR POLYNUCLEOTIDES.

PMID- 16589941
TI  - THE OPTICAL ROTATORY DISPERSION OF SIMPLE POLYPEPTIDES. II.

PMID- 16589942
TI  - SYNERGISM OF TWO CYTOPLASMICALLY INHERITED MUTANTS IN NEUROSPORA CRASSA.

PMID- 16589943
TI  - MUTATION RATES OF SEVERAL GENE LOCI IN NEUROSPORA.

PMID- 16589945
TI  - ONE-DIMENSIONAL CONTINUOUS CURVES.

PMID- 16589944
TI  - SQUARE-INTEGRABLE DIFFERENTIALS ON OPEN RIEMANN SURFACES.

PMID- 16589946
TI  - ON POWER SERIES WITH UNBOUNDED CLUSTER SETS, AND FUNCTIONS OF CLASS H(2) WITH
      MEAGER SETS OF RADIAL CONTINUITY.

PMID- 16589947
TI  - SINGULARITIES OF ANALYTICAL DIFFERENTIAL SYSTEMS IN THE PLANE.

PMID- 16589948
TI  - DYNAMIC PROGRAMMING AND LAGRANGE MULTIPLIERS.

PMID- 16589949
TI  - EIGENFUNCTION EXPANSIONS FOR FORMALLY SELF-ADJOINT PARTIAL DIFFERENTIAL
      OPERATORS. I.

PMID- 16589950
TI  - ON THE IMBEDDING OF A FINITE COMMUTATIVE SEMIGROUP OF IDEMPOTENTS IN A UNIQUELY
      FACTORABLE SEMIGROUP.

PMID- 16589951
TI  - PARTIAL FOURIER SYNTHESES AND THEIR APPLICATION TO THE SOLUTION OF CERTAIN
      CRYSTAL STRUCTURES.

PMID- 16589952
TI  - A NEW THEORY OF LIMB INDUCTION.

PMID- 16589953
TI  - ABNORMAL BRAIN SIZE AND FUNCTIONAL REGULATION IN FUNDULUS.

PMID- 16589954
TI  - THE FORMATION OF INFECTIOUS NUCLEOPROTEIN FROM TOBACCO MOSAIC VIRUS PROTEIN AND
      TOBACCO LEAF DNA.

PMID- 16589955
TI  - REVERSAL OF THE LIGHT INHIBITION OF PEA STEM GROWTH BY THE GIBBERELLINS.

PMID- 16589956
TI  - THE CONTINUOUS SUBMERGED CULTIVATION OF PLANT TISSUE AS SINGLE CELLS.

PMID- 16589957
TI  - ON THE UNIQUENESS OF IDEAL GAS FLOWS WITH A STRAIGHT STREAMLINE.

PMID- 16589958
TI  - AN ESTIMATE OF THE MUTATIONAL DAMAGE IN MAN FROM DATA ON CONSANGUINEOUS
      MARRIAGES.

PMID- 16589959
TI  - TWO LATE-GLACIAL DEPOSITS IN SOUTHERN CONNECTICUT.

PMID- 16589960
TI  - HYDRODYNAMICAL STABILITY AND POINCARE-LYAPUNOV THEORY. I.

PMID- 16589961
TI  - EIGENFUNCTION EXPANSIONS FOR FORMALLY SELF-ADJOINT PARTIAL DIFFERENTIAL
      OPERATORS. II.

PMID- 16589962
TI  - THE PROPAGATION OF DISCONTINUITIES IN WAVE MOTION.

PMID- 16589963
TI  - MARKET EQUILIBRIUM.

PMID- 16589964
TI  - A UNIFIED THEORY OF GENERAL RELATIVITY OF GRAVITATION AND ELECTROMAGNETISM. III.

PMID- 16589965
TI  - ON CANONICAL CONSTRUCTIONS. II.

PMID- 16589966
TI  - ASYMPTOTIC SPOTS OF ENTIRE AND MEROMORPHIC FUNCTIONS.

PMID- 16589967
TI  - THE UNIQUENESS OF DOUBLE TRIGONOMETRIC SERIES UNDER CIRCULAR CONVERGENCE.

PMID- 16589968
TI  - THE COSMIC ABUNDANCES OF POTASSIUM, URANIUM, AND THORIUM AND THE HEAT BALANCES OF
      THE EARTH, THE MOON, AND MARS.

PMID- 16589969
TI  - THE ISOLATION OF A NEW VIRUS ASSOCIATED WITH RESPIRATORY CLINICAL DISEASE IN
      HUMANS.

PMID- 16589970
TI  - REVERSIBILITY AND EQUILIBRIUM OF THE GLUTAMINASE REACTION OBSERVED
      CALORIMETRICALLY TO FIND THE FREE ENERGY OF ADENOSINE TRIPHOSPHATE HYDROLYSIS.

PMID- 16589971
TI  - ON THE FUNCTIONS OF X-IRRADIATED "FEEDER" CELLS IN SUPPORTING GROWTH OF SINGLE
      MAMMALIAN CELLS.

PMID- 16589973
TI  - A NEW METHOD FOR THE MEASUREMENT OF SELF-DIFFUSION.

PMID- 16589972
TI  - THE PRODUCTION OF TUMOROUS ABNORMALITIES IN FERN PROTHALLI BY IONIZING
      RADIATIONS.

PMID- 16589974
TI  - PARABOLIC SYSTEMS OF DIFFERENTIAL EQUATIONS WITH TIME-DEPENDENT COEFFICIENTS.

PMID- 16589975
TI  - ON ABSOLUTE CONVERGENCE OF FOURIER SERIES.

PMID- 16589976
TI  - A SEQUENTIAL DECISION PROBLEM WITH A FINITE MEMORY.

PMID- 16589977
TI  - SLIP SURFACES IN PLASTIC SOLIDS.

PMID- 16589978
TI  - NOTE ON DEGREE OF APPROXIMATION TO ANALYTIC FUNCTIONS BY RATIONAL FUNCTIONS WITH
      PREASSIGNED POLES.

PMID- 16589979
TI  - SIMPLIFIED MODEL TO DEMONSTRATE THE ENERGY FLOW AND FORMATION OF TRAVELING WAVES
      SIMILAR TO THOSE FOUND IN THE COCHLEA.

PMID- 16589980
TI  - CURRENT RESEARCH FINDINGS ON RADIOACTIVE FALLOUT.

PMID- 16589981
TI  - AUDITORY RESPONSES IN THE COMMON BOX TURTLE.

PMID- 16589982
TI  - ARE CHLOROPLASTS SEMICONDUCTORS?

PMID- 16589983
TI  - STUDIES ON THE IMMUNOLOGICAL OVERLAP AMONG CERTAIN ARTHROPOD-BORNE VIRUSES. II.
      THE ROLE OF SEROLOGIC RELATIONSHIPS IN EXPERIMENTAL VACCINATION PROCEDURES.

PMID- 16589984
TI  - THE ORGANIZATION AND DUPLICATION OF CHROMOSOMES AS REVEALED BY AUTORADIOGRAPHIC
      STUDIES USING TRITIUM-LABELED THYMIDINEE.

PMID- 16589985
TI  - A METHOD FOR INCREASING BRAIN SEROTONIN WITHOUT INCURRING SOME OF THE PERIPHERAL
      EFFECTS OF THE HORMONE.

PMID- 16589986
TI  - SOME FACTORS INFLUENCING THE LONG-WAVE LIMIT OF PHOTOSYNTHESIS.

PMID- 16589987
TI  - THE SYMMETRY OF DENDRITIC SNOW CRYSTALS.

PMID- 16589988
TI  - EXCITATIONS AND POLYMERIZATION.

PMID- 16589989
TI  - MALE SEGREGATION RATIO ADVANTAGE AS A FACTOR IN MAINTAINING LETHAL ALLELES IN
      WILD POPULATIONS OF HOUSE MICE.

PMID- 16589990
TI  - EVIDENCE OF EVOLUTIONARY FORCES LEADING TO THE SPREAD OF LETHAL GENES IN WILD
      POPULATIONS OF HOUSE MICE.

PMID- 16589991
TI  - COMBINATORIAL PROBLEMS IN THE THEORY OF GRAPHS. IV.

PMID- 16589992
TI  - INDICES OF RANK AND OF SINGULARITY ON ABELIAN VARIETIES.

PMID- 16589993
TI  - ON DEHN'S LEMMA AND THE ASPHERICITY OF KNOTS.

PMID- 16589994
TI  - FUNCTION RINGS ON THE CIRCLE.

PMID- 16589995
TI  - INFLUENCE OF THE TYPE OF INSEMINATED FEMALE ON THE LETHAL FREQUENCY IN THE X
      CHROMOSOME FROM THE MALE.

PMID- 16589997
TI  - THE METABOLISM OF L-THREONINE AND GLYCINE BY Escherichia coli.

PMID- 16589996
TI  - THE DEVELOPMENT IN VITRO OF CHIMERIC AGGREGATES OF DISSOCIATED EMBRYONIC CHICK
      AND MOUSE CELLS.

PMID- 16589998
TI  - STERILE INDUCTION OF CROWN-GALL TUMORS ON CARROT TISSUES IN VITRO.

PMID- 16589999
TI  - THE STRUCTURE OF ALPHA KERATIN.

PMID- 16590000
TI  - THE STRUCTURE OF COLLAGEN.

PMID- 16590002
TI  - CONTRIBUTIONS TO THE THEORY OF THE CONTINUOUS BACTERIAL GROWTH APPARATUS: I.
      KINETICS OF GROWTH OF HOMOGENEOUS POPULATIONS.

PMID- 16590001
TI  - THE CONTRIBUTION OF THE alpha-HELICAL CONFIGURATION TO THE OPTICAL ROTATION OF
      POLYPEPTIDES AND PROTEINS.

PMID- 16590003
TI  - HETEROSIS AND ELIMINATION OF WEAK HOMOZYGOTES IN NATURAL POPULATIONS OF THREE
      RELATED SPECIES OF Drosophila.

PMID- 16590004
TI  - REGULARITY THEOREMS FOR SOLUTIONS OF PARTIAL DIFFERENTIAL EQUATIONS WITH VARIABLE
      COEFFICIENTS.

PMID- 16590005
TI  - TWO RECURSIVELY ENUMERABLE SETS OF INCOMPARABLE DEGREES OF UNSOLVABILITY
      (SOLUTION OF POST'S PROBLEM, 1944).

PMID- 16590006
TI  - A THEOREM ON STABILITY OF COMPLEX STRUCTURES.

PMID- 16590008
TI  - INTEGRATION OF A DIFFERENTIAL FORM ON AN ANALYTIC COMPLEX SUBVARIETY.

PMID- 16590007
TI  - ON THE SPECTRAL SEQUENCE OF A FIBER SPACE. II.

PMID- 16590009
TI  - APPLICATION OF HILBERT SPACE METHODS TO LIE GROUPS ACTING ON A DIFFERENTIABLE
      MANIFOLD.

PMID- 16590010
TI  - EFFECT OF RIBONUCLEASE ON CROSSING OVER IN Drosophila.

PMID- 16590011
TI  - THE NATURE OF THE CHANGES EFFECTED IN CHROMOSOMAL MATERIALS BY THE CHELATING
      AGENT EDTA.

PMID- 16590012
TI  - THE ASYMPTOTIC DISTRIBUTION OF EIGENFUNCTIONS AND EIGENVALUES FOR SEMI-ELLIPTIC
      DIFFERENTIAL OPERATIONS.

PMID- 16590014
TI  - ZEROS OF NEIGHBORING HOLOMORPHIC FUNCTIONS.

PMID- 16590013
TI  - IRREDUCIBLE OPERATOR ALGEBRAS.

PMID- 16590015
TI  - A PRELIMINARY NOTE ON EXCITATION-CONTRACTION COUPLING.

PMID- 16590017
TI  - THREE DIPLOID CHROMOSOME NUMBERS OF MAN.

PMID- 16590016
TI  - THE PROBLEM OF DOMINANT LETHALS IN Drosophila Melanogaster FEMALES.

PMID- 16590018
TI  - ON THE RELATIVE ABUNDANCE OF BIRD SPECIES.

PMID- 16590019
TI  - THE OXIDATION OF REDUCED TRIPHOSPHOPYRIDINE NUCLEOTIDE AS MEDIATED BY THE
      TRANSHYDROGENASE REACTION AND ITS INHIBITION BY THYROXINE.

PMID- 16590020
TI  - INTERRELATIONSHIP BETWEEN VITAMIN E AND LIPIDE COFACTOR IN THE CYTOCHROME C
      REDUCTASE SYSTEM.

PMID- 16590021
TI  - MEIOTROPHIC MUTANTS OF Pasteurella Pestis AND THEIR USE IN THE ELUCIDATION OF
      NUTRITIONAL REQUIREMENTS.

PMID- 16590022
TI  - COMPETITIVE BINDING OF ATP AND ACRIDINE ORANGE BY MUSCLE.

PMID- 16590023
TI  - THE BEHAVIOR OF TWO FOREIGN PROTEIN ANTIGENS IN MICE DURING INHIBITION OF
      ANTIBODY FORMATION BY CORTISONE.

PMID- 16590024
TI  - PHOTO SPIN RESONANCE IN CHLOROPHYLL-CONTAINING PLANT MATERIAL.

PMID- 16590025
TI  - BIOCHEMICAL BASIS FOR THE TOXICITY OF PENTACHLOROPHENOL.

PMID- 16590026
TI  - EVIDENCE FOR "GIBBERELLIN-LIKE" SUBSTANCES FROM FLOWERING PLANTS.

PMID- 16590027
TI  - THE EFFECT OF HETEROZYGOSITY FOR NEW MUTATIONS ON VIABILITY IN Drosophila: A
      PRELIMINARY REPORT.

PMID- 16590028
TI  - SPHERICAL FUNCTIONS ON A SEMISIMPLE LIE GROUP.

PMID- 16590029
TI  - ON THE HOMOLOGY OF K(pi, n).

PMID- 16590030
TI  - THE DIVERGENCE THEOREM WITHOUT DIFFERENTIABILITY CONDITIONS.

PMID- 16590031
TI  - DIFFUSION OF PARTICLES WITH MEMORY.

PMID- 16590032
TI  - CODES WITHOUT COMMAS.

PMID- 16590033
TI  - STRAIN ELECTROMETRY AND CORROSION I. GENERAL CONSIDERATIONS ON INTERFACIAL
      ELECTRICAL TRANSIENTS.

PMID- 16590034
TI  - VARIATION OF REACTION RATE WITH VIBRATIONAL STATE.

PMID- 16590035
TI  - INFLUENCE OF NOTOCHORD ON DIFFERENTIATION OF STRIATED MUSCLE IN AMBYSTOMA.

PMID- 16590036
TI  - A STUDY OF ASYMMETRY IN THE DEVELOPING GUT.

PMID- 16590037
TI  - OCCURRENCE OF URINARY ACID MUCOPOLYSACCHARIDES IN THE HURLER SYNDROME.

PMID- 16590038
TI  - ASYMMETRIC DISTRIBUTION OF C IN SUGARS FORMED DURING PHOTOSYNTHESIS.

PMID- 16590039
TI  - MULTIPLICATION OF ANIMAL CELLS IN SUSPENSION MEASURED BY COLONY COUNTS.

PMID- 16590040
TI  - ON THE DISTRIBUTION OF PURINE AND PYRIMIDINE BASES IN THE NUCLEIC ACID OF TOBACCO
      MOSAIC VIRUS.

PMID- 16590041
TI  - MOLECULAR BASIS OF BIOLOGICAL STABILITY TO HIGH TEMPERATURES.

PMID- 16590042
TI  - ON EXCITATION OF BIOLOGICAL SUBSTANCES.

PMID- 16590043
TI  - REPRESSED AND INDUCED ENZYME FORMATION: A UNIFIED HYPOTHESIS.

PMID- 16590045
TI  - THE NORM FORM OF A RATIONAL DIVISION ALGEBRA.

PMID- 16590044
TI  - THE SITES OF ORTHOPHOSPHATE UPTAKE BY BARLEY ROOTS.

PMID- 16590046
TI  - THE RANDOM FUNCTIONS OF COSMIC-RAY CASCADES.

PMID- 16590047
TI  - THE IDENTITY OF THE WEAK AND STRONG EXTENSIONS OF A LINEAR ELLIPTIC DIFFERENTIAL
      OPERATOR.

PMID- 16590048
TI  - ON THE PRINCIPLE OF INVARIANT IMBEDDING AND DIFFUSE REFLECTION FROM CYLINDRICAL
      REGIONS.

PMID- 16590049
TI  - ON THE PRINCIPLE OF INVARIANT IMBEDDING AND ONE-DIMENSIONAL NEUTRON
      MULTIPLICATION.

PMID- 16590050
TI  - ON THE EXPANSION OF FUNCTIONS WHICH SATISFY FOUR BOUNDARY CONDITIONS.

PMID- 16590051
TI  - ELECTROMAGNETIC DETERMINATION OF REGIONAL BLOOD FLOW IN UNANESTHETIZED ANIMALS.

PMID- 16590052
TI  - ON THE BINDING OF ADENOSINE TRIPHOSPHATE BY ACTOMYOSIN.

PMID- 16590053
TI  - RESULTS OF INVERSION OF NEURAL PLATE MATERIAL.

PMID- 16590054
TI  - THE PROSTHETIC GROUP OF PHOSPHORYLASE.

PMID- 16590055
TI  - ENZYME INDUCTION AS AN ALL-OR-NONE PHENOMENON.

PMID- 16590056
TI  - THE ISOLATION OF LYSOLECITHIN FROM HUMAN SERUM.

PMID- 16590057
TI  - APICAL MERISTEMS OF VEGETATIVE SHOOTS AND STROBILI IN CERTAIN GYMNOSPERMS.

PMID- 16590058
TI  - STRONTIUM 90 IN NORTH ATLANTIC SURFACE WATER.

PMID- 16590059
TI  - EQUILIBRIUM SEDIMENTATION OF MACROMOLECULES IN DENSITY GRADIENTS.

PMID- 16590060
TI  - THE ROLE OF DEOXYRIBONUCLEIC ACID AND OTHER POLYNUCLEOTIDES IN ATP SYNTHESIS BY
      ISOLATED CELL NUCLEI.

PMID- 16590061
TI  - TRANSMISSIBLE VARIATIONS IN THE CYTOPLASM WITHIN SPECIES OF HIGHER PLANTS.

PMID- 16590062
TI  - FREE AMINO ACID DIFFERENCES BETWEEN CYTOPLASMIC MALE STERILE AND NORMAL FERTILE
      ANTHERS.

PMID- 16590063
TI  - THE EFFECT OF X-RAYS ON THE Drosophila TESTIS AND A METHOD FOR OBTAINING
      SPERMATOGONIAL MUTATION RATES.

PMID- 16590064
TI  - ON A WEDDERBURN-ARTIN STRUCTURE THEORY OF A POTENT SEMIRING.

PMID- 16590065
TI  - ON THE BASIC APPROXIMATION THEOREM FOR SEMIGROUPS OF LINEAR OPERATORS.

PMID- 16590066
TI  - PROOF OF A THEOREM DISCOVERED BY MURNAGHAN.

PMID- 16590068
TI  - N.A.S. Organization: July 1, 1957.

PMID- 16590067
TI  - THE IDENTITY OF THE WEAK AND STRONG EXTENSIONS OF A LINEAR ELLIPTIC DIFFERENTIAL
      OPERATOR: II.

PMID- 16590069
TI  - ON THE IMPOSSIBILITY OF ALL OVERLAPPING TRIPLET CODES IN INFORMATION TRANSFER
      FROM NUCLEIC ACID TO PROTEINS.

PMID- 16590070
TI  - INFECTION OF PROTOPLASTS BY DISRUPTED T2 VIRUS.

PMID- 16590071
TI  - INCORPORATION OF RADIOACTIVE CARBON INTO A PTERIDINE OF A BLUE-GREEN ALGA.

PMID- 16590072
TI  - IONIC SEMIPERMEABILITY AS A BULK PROPERTY.

PMID- 16590073
TI  - THE EFFECT OF GIBBERELLIN UPON FLOWER FORMATION.

PMID- 16590074
TI  - CHANGES IN PROTEIN TOPOGRAPHY UPON OXYGENATION.

PMID- 16590075
TI  - VECTOR MODEL FOR INDIRECT PROTON HYPERFINE INTERACTIONS IN pi-ELECTRON RADICALS.

PMID- 16590076
TI  - CRITIQUE OF THE THEORY OF OPTICAL ACTIVITY OF HELICAL POLYMERS.

PMID- 16590077
TI  - A REMARKABLE ACTION OF THE MUTANT "RUDIMENTARY" IN Drosophila Melanogaster.

PMID- 16590078
TI  - SPECIAL PROBLEMS INHERENT IN THE STUDY OF HUMAN GENETICS WITH PARTICULAR
      REFERENCE TO THE EVALUATION OF RADIATION RISKS.

PMID- 16590079
TI  - THE SCOPE OF GENETICS.

PMID- 16590080
TI  - DYNAMIC PROGRAMMING AND STATISTICAL COMMUNICATION THEORY.

PMID- 16590081
TI  - SOLUTION OF THE BURNSIDE PROBLEM FOR EXPONENT 6.

PMID- 16590082
TI  - PARABOLIC EQUATIONS.

PMID- 16590083
TI  - RADIOACTIVE FALLOUT.

PMID- 16590085
TI  - A LABORATORY STUDY OF THE EFFECT OF REMOVAL OF NEW BORN ANIMALS FROM A
      POPULATION.

PMID- 16590084
TI  - THE LOCALIZATION OF BASIC PROTEINS IN THE NUCLEI OF LARVAL Drosophila SALIVARY
      GLANDS.

PMID- 16590086
TI  - TISSUE STORAGE OF MUCOPOLYSACCHARIDES IN HURLER-PFAUNDLER'S DISEASE.

PMID- 16590087
TI  - VACCINE FOR THE PREVENTION IN HUMANS OF COLDLIKE SYMPTOMS ASSOCIATED WITH THE JH
      VIRUS.

PMID- 16590088
TI  - OCCURRENCE OF ORNITHINE delta-TRANSAMINASE: A DICHOTOMY.

PMID- 16590089
TI  - ON THE MECHANISM OF TEMPERATURE INDEPENDENCE IN A BIOLOGICAL CLOCK.

PMID- 16590091
TI  - ON THE ORIGIN OF POTENTIAL BARRIERS TO INTERNAL ROTATION IN MOLECULES.

PMID- 16590090
TI  - CATALYTIC AND POLYMERIZATION-DIRECTING PROPERTIES OF MINERAL SURFACES.

PMID- 16590092
TI  - SOME ASPECTS OF RIBONUCLEIC ACID SYNTHESIS IN ISOLATED CELL NUCLEI.

PMID- 16590093
TI  - SEQUENTIAL BLOCKADE IN ADENINE BIOSYNTHESIS BY GENETIC LOSS OF AN APPARENT
      BIFUNCTIONAL DEACYLASE.

PMID- 16590094
TI  - BLUE RIDGE TECTONICS BETWEEN HARRISBURG, PENNSYLVANIA AND ASHEVILLE, NORTH
      CAROLINA.

PMID- 16590095
TI  - FUNCTIONAL EQUATIONS IN THE THEORY OF DYNAMIC PROGRAMMING: VIII. THE VARIATION OF
      GREEN'S FUNCTIONS FOR THE ONE-DIMENSIONAL CASE.

PMID- 16590096
TI  - TWO THEOREMS IN GRAPH THEORY.

PMID- 16590097
TI  - MATHEMATICS: POLYNOMIALS OF BEST APPROXIMATION ON A REAL FINITE POINT SET.

PMID- 16590098
TI  - SPECIFICITY OF INTERMOLECULAR FORCES DUE TO QUANTUM-MECHANICAL AND THERMAL CHARGE
      FLUCTUATIONS.

PMID- 16590099
TI  - STUDIES ON RIBONUCLEIC ACID ISOLATED FROM EHRLICH ASCITES TUMOR CELLS.

PMID- 16590100
TI  - MACROMOLECULAR AGGREGATION STATES IN RELATION TO MINERALIZATION: THE COLLAGEN
      HYDROXYAPATITE SYSTEM AS STUDIED IN VITRO.

PMID- 16590101
TI  - SPERMINE AND RELATED POLYAMINES AS GROWTH STIMULANTS FOR Lactobacillus Casei.

PMID- 16590102
TI  - A RELATION OF NUCLEIC ACID SYNTHESIS TO RADIATION-INDUCED MUTATION FREQUENCY IN
      BACTERIA.

PMID- 16590103
TI  - THE FORMATION OF ANTIBODIES IN MAN AFTER INJECTION OF PNEUMOCOCCAL
      POLYSACCHARIDES.

PMID- 16590104
TI  - CELL DIVISION IN ISOLATED SINGLE PLANT CELLS IN VITRO.

PMID- 16590105
TI  - EVIDENCE FOR AN UNSTABLE CO(2) FIXATION PRODUCT IN ALGAL CELLS.

PMID- 16590106
TI  - THE LUMINESCENCE OF CHLOROPHYLL-CONTAINING PLANT MATERIAL.

PMID- 16590107
TI  - INHERITANCE IN Nicotiana Tabacum. XXVIII. THE CYTOGENETICS OF INTROGRESSION.

PMID- 16590108
TI  - CONTROL OF SEX RATIO IN RABBITS BY ELECTROPHORESIS OF SPERMATOZOA.

PMID- 16590109
TI  - EXTRANUCLEAR TRANSMISSION IN YEAST HETEROKARYONS.

PMID- 16590110
TI  - A SEMIGRAPHICAL METHOD FOR THE ANALYSIS OF COMPLEX PROBLEMS.

PMID- 16590111
TI  - TERMINAL CONTROL, TIME LAGS, AND DYNAMIC PROGRAMMING.

PMID- 16590112
TI  - RANDOM WALK, SCATTERING, AND INVARIANT IMBEDDING I. ONE-DIMENSIONAL DISCRETE
      CASE.

PMID- 16590113
TI  - THE STABLE HOMOTOPY OF THE CLASSICAL GROUPS.

PMID- 16590114
TI  - A GENERALIZATION OF WHITNEY'S THEOREM ON IDEALS OF DIFFERENTIABLE FUNCTIONS.

PMID- 16590115
TI  - PROTEIN SYNTHESIS AND TISSUE INTEGRITY IN THE CORNEA OF THE DEVELOPING CHICK
      EMBRYO.

PMID- 16590116
TI  - SPECTRAL LUMINOSITY CURVES FOR PROTANOPIC, DEUTERANOPIC, AND NORMAL SUBJECTS.

PMID- 16590117
TI  - ON SOME PHENOMENA IN DROSOPHILA RELATED TO SO-CALLED GENIC CONVERSION.

PMID- 16590118
TI  - THE INFECTION OF SUB-CELLULAR ESCHERICHIA COLI, STRAIN B, WITH A DNA PREPARATION
      FROM T2 BACTERIOPHAGE.

PMID- 16590119
TI  - GENETIC INTERACTION AMONG STREPTOMYCETES: HETEROKARYOSIS AND SYNKARYOSIS.

PMID- 16590120
TI  - THE ACTIVATION OF METABOLIC SYSTEMS DURING CROWN-GALL TUMOR-CELL FORMATION.

PMID- 16590121
TI  - INDUCTION OF BOLTING AND FLOWERING IN HYOSCYAMUS AND SAMOLUS BY A GIBBERELLIN
      LIKE MATERIAL FROM A SEED PLANT.

PMID- 16590122
TI  - DISPROPORTIONATE SYNTHESIS OF DNA IN A POLYTENE CHROMOSOME REGION.

PMID- 16590123
TI  - HYPOTHESIS FOR THE MECHANISM OF ACTION OF CHYMOTRYPSIN.

PMID- 16590124
TI  - MODIFICATION OF RADIATION-INDUCED INJURY BY POSTTREATMENT WITH OXYGEN.

PMID- 16590125
TI  - TRANSFORMATION GROUPS WITH TWO CLASSES OF ORBITS.

PMID- 16590126
TI  - ON UNITARY REPRESENTATIONS OF NILPOTENT LIE GROUPS.

PMID- 16590127
TI  - PRODUCTS IN HOMOTOPY AND HOMOLOGY GROUPS.

PMID- 16590128
TI  - THE MULTIDIMENSIONAL PREDICTION PROBLEM.

PMID- 16590129
TI  - UNIFORM CONVERGENCE FOR MONOTONE MAPPINGS.

PMID- 16590130
TI  - SOLUTION OF THE BOLTZMANN-HILBERT INTEGRAL EQUATION II. THE COEFFICIENTS OF
      VISCOSITY AND HEAT CONDUCTION.

PMID- 16590131
TI  - MUTAGENIC EFFECTS OF HIGH OXYGEN TENSIONS ON ESCHERICHIA COLI.

PMID- 16590132
TI  - MOLECULAR STRIAE FROM AN INDANTHRENE DYE.

PMID- 16590133
TI  - THE INCORPORATION OF C-ADENINE AND C-PHENYLALANINE BY DEVELOPING ROOT-TIP CELLS.

PMID- 16590134
TI  - THE OPTICAL ROTATORY DISPERSION OF THE alpha-HELIX.

PMID- 16590135
TI  - INVARIABLE GENETIC CHANGE IN MAIZE PLANTS HETEROZYGOUS FOR MARBLED ALEURONE.

PMID- 16590136
TI  - SIBLING RECOMBINANTS IN ZYGOTE PEDIGREES OF ESCHERICHIA COLI.

PMID- 16590137
TI  - CONGRUENCES INVOLVING COMBINATIONS OF THE BERNOULLI AND FIBONACCI NUMBERS.

PMID- 16590138
TI  - GENERAL SOLUTION FOR THE STRESSES IN A CURVED MEMBRANE.

PMID- 16590140
TI  - ON THE MAGNETIC ASYMMETRY OF MUSCLE FIBERS.

PMID- 16590139
TI  - SOME STATISTICAL OBSERVATIONS ON A CO-OPERATIVE STUDY OF HUMAN PULMONARY
      PATHOLOGY.

PMID- 16590141
TI  - THE MECHANISM OF ACTION OF ALDOLASE AND THE ASYMMETRIC LABELING OF HEXOSE.

PMID- 16590142
TI  - ACTIVATION OF HYDROGEN TRANSFER BETWEEN PYRIDINE NUCLEOTIDES BY STEROID HORMONES.

PMID- 16590143
TI  - CONDUCTANCE OF TETRABUTYLAMMONIUM TETRAPHENYLBORIDE.

PMID- 16590144
TI  - MODIFICATION OF CELL-MIGRATION PATTERNS IN THE EARLY CHICK EMBRYO.

PMID- 16590145
TI  - CHROMOSOMAL POLYMORPHISM IN CARIBBEAN ISLAND POPULATIONS OF DROSOPHILA
      WILLISTONI.

PMID- 16590146
TI  - MOLECULAR GROWTH REQUIREMENTS OF SINGLE MAMMALIAN CELLS: THE ACTION OF FETUIN IN
      PROMOTING CELL ATTACHMENT TO GLASS.

PMID- 16590147
TI  - ON THE CONCEPT OF SURFACE INTEGRAL.

PMID- 16590148
TI  - SPECTRAL REPRESENTATION OF SEMIGROUPS OF NORMAL OPERATORS.

PMID- 16590150
TI  - CHEMICAL AERONOMY.

PMID- 16590149
TI  - THE SPECTRAL LUMINOSITY CURVES FOR A DICHROMATIC EYE AND A NORMAL EYE IN THE SAME
      PERSON.

PMID- 16590151
TI  - INDUCTION OF SPECIFIC MUTATIONS WITH 5-BROMOURACIL.

PMID- 16590152
TI  - A THEORY OF OPTIMUM CONDITIONS FOR PHASE TRANSITIONS.

PMID- 16590153
TI  - THE VISUAL SYSTEM OF THE HONEYBEE.

PMID- 16590154
TI  - THE LUCIFERIN-LUCIFERASE REACTION IN A FISH, PARAPRIACANTHUS BERYCIFORMIS, OF
      NEWLY DISCOVERED LUMINESCENCE.

PMID- 16590155
TI  - THE ACTION OF LIGHT ON RHODOPSIN.

PMID- 16590156
TI  - ON RESONANCE TRANSFER OF EXCITATION ENERGY BETWEEN AROMATIC AMINOACIDS IN
      PROTEINS.

PMID- 16590157
TI  - THE DEPENDENCE OF PNEUMOCOCCAL TRANSFORMATION ON THE MOLECULAR WEIGHT OF
      DEOXYRIBOSE NUCLEIC ACID.

PMID- 16590158
TI  - OBSERVATIONS IN MYELIN STRUCTURE: INCISURES AND NODAL REGIONS.

PMID- 16590159
TI  - THE INACTIVATION OF GROWTH-PROMOTING DISLOCATIONS WITH TEMPERATURE, PRESSURE, AND
      POISONS.

PMID- 16590160
TI  - ON THE ENZYMIC ACTIVITY OF SUBTILISIN-MODIFIED RIBONUCLEASE.

PMID- 16590161
TI  - ON THE MECHANISM OF SQUALENE BIOGENESIS.

PMID- 16590162
TI  - THE INCORPORATION OF AMINO ACIDS INTO RIBONUCLEIC ACID.

PMID- 16590163
TI  - FLUORESCENCE STUDIES OF COENZYME BINDING TO DEHYDROGENASES.

PMID- 16590164
TI  - INACTIVATION OF HUMAN ERYTHROCYTE AGGLUTINOGENS M AND N BY INFLUENZA VIRUSES AND
      RECEPTOR-DESTROYING ENZYME.

PMID- 16590165
TI  - AMINO ACID INCORPORATION IN PIGEON PANCREAS FRACTIONS.

PMID- 16590166
TI  - A PROBABLE MECHANISM OF ACTION OF SEROTONIN.

PMID- 16590167
TI  - EXTREMAL PRINCIPLES FOR SIMULATING TRAFFIC FLOW IN A NETWORK.

PMID- 16590168
TI  - EARLY UNSTABLE CO(2) FIXATION PRODUCTS IN PHOTOSYNTHESIS.

PMID- 16590169
TI  - THE NATURE OF BOND ORBITALS AND THE ORIGIN OF POTENTIAL BARRIERS TO INTERNAL
      ROTATION IN MOLECULES.

PMID- 16590170
TI  - IDENTIFICATION OF BLOOD CHARACTERISTICS COMMON TO ALCOHOLIC MALES.

PMID- 16590171
TI  - AN EXAMPLE OF A NONNORMAL DISTRIBUTION WHERE THE QUOTIENT FOLLOWS THE CAUCHY LAW.

PMID- 16590172
TI  - SPIN, STATISTICS, AND THE TCP THEOREM.

PMID- 16590173
TI  - SOME MECHANISMS OF CONSCIOUSNESS DISCOVERED DURING ELECTRICAL STIMULATION OF THE
      BRAIN.

PMID- 16590174
TI  - Chairman's Introduction: Some Facts and Problems.

PMID- 16590175
TI  - Intermediate Reactions in Amino Acid Incorporation.

PMID- 16590176
TI  - An Enzymatic Mechanism for Linking Amino Acids to RNA.

PMID- 16590177
TI  - Some Problems Concerning the Activation of Amino Acids.

PMID- 16590178
TI  - Tracing of the In Vivo Path from Amino Acid to Protein.

PMID- 16590180
TI  - CONCERNING THE ORIGIN OF BACTERIAL VIRUSES.

PMID- 16590179
TI  - Application of a Theory of Enzyme Specificity to Protein Synthesis.

PMID- 16590181
TI  - DEHYDRATED MUSCLE FIBERS.

PMID- 16590182
TI  - PTERIDINES IN PHOTOSYNTHESIS.

PMID- 16590183
TI  - THE ENZYMATIC ACTIVITY ASSOCIATED WITH THE PROTEIN IMMUNOLOGICALLY RELATED TO
      TRYPTOPHAN SYNTHETASE.

PMID- 16590184
TI  - A PRELIMINARY INVESTIGATION OF PSEUDOALLELISM AT THE NOTCH LOCUS OF Drosophila
      Melanogaster.

PMID- 16590185
TI  - PRINCIPLE OF MINIMUM BENDING OF LOCALIZED AND DELOCALIZED ORBITALS; ETHANE
      BARRIER AND RELATED EFFECTS.

PMID- 16590186
TI  - THE PATH OF CARBON IN PHOTOSYNTHESIS. XXII. THE IDENTIFICATION OF CARBOXY
      KETOPENTITOL DIPHOSPHATES AS PRODUCTS OF PHOTOSYNTHESIS.

PMID- 16590187
TI  - MEASURES ORTHOGONAL TO POLYNOMIALS.

PMID- 16590188
TI  - NON-PARALLELIZABILITY OF THE n-SPHERE FOR n > 7.

PMID- 16590189
TI  - ON FORCE-FREE MAGNETIC FIELDS.

PMID- 16590190
TI  - MONTHLY CYCLES IN AN ORGANISM IN CONSTANT CONDITIONS DURING 1956 AND 1957.

PMID- 16590191
TI  - DEVELOPMENT OF COLLAGEN IN THE FROG EMBRYO.

PMID- 16590192
TI  - AMINO ACID INCORPORATION AND THE REVERSION OF ITS INITIAL PHASE WITH CELL-FREE
      TETRAHYMENA PREPARATIONS.

PMID- 16590193
TI  - SOLUTION OF A PAIR OF INTEGRAL EQUATIONS FROM ELASTOSTATICS.

PMID- 16590195
TI  - NOTE TO MY PAPER "ON MEMBRANES AND PLATES".

PMID- 16590194
TI  - CLASS NUMBER OF A DEFINITE QUATERNION WITH PRIM DISCRIMINANT.

PMID- 16590196
TI  - INVARIANT IMBEDDING, WAVE PROPAGATION, AND THE WKB APPROXIMATION.

PMID- 16590197
TI  - IVARIANT IMBEDDING RELATION FOR THE PRINCIPLES OF INVARIANCE.

PMID- 16590198
TI  - FUNCTIONAL RELATIONS FOR THE R AND T OPERATORS ON PLANE-PARALLEL MEDIA.

PMID- 16590199
TI  - TIME-DEPENDENT PRINCIPLES OF INVARIANCE.

PMID- 16590200
TI  - ABERRANT SEGREGATION AND PSEUDOALLELISM AT THE GARNET LOCUS IN DROSOPHILA
      MELANOGASTER.

PMID- 16590201
TI  - PLANT TUMORS: Introduction.

PMID- 16590202
TI  - A Tree Tumor of Unknown Origin.

PMID- 16590203
TI  - A Physiological Basis for Autonomous Growth of the Crown-Gall Tumor Cell.

PMID- 16590204
TI  - Activation of Metabolic Systems During Tumor-Cell Formation.

PMID- 16590206
TI  - Wound-Tumor.

PMID- 16590205
TI  - Stimulation or Inhibition of Virus of Infected and Insect-Gall Tissues and Single
      Cell Clones.

PMID- 16590207
TI  - Conclusions.

PMID- 16590208
TI  - PROTEIN TURNOVER IN MICRO-ORGANISMS.

PMID- 16590209
TI  - THE TRANSFER OF IRRADIATION-ELICITED INDUCTION IN A LYSOGENIC ORGANISM.

PMID- 16590210
TI  - EVIDENCE FROM TETRAD ANALYSIS FOR BOTH NORMAL AND ABERRANT RECOMBINATION BETWEEN
      ALLELIC MUTANTS IN Neurospora Crassa.

PMID- 16590211
TI  - MODIFICATION OF ULTRAVIOLET-INDUCED MUTATION FREQUENCY AND SURVIVAL IN BACTERIA
      BY POST-IRRADIATION TR000EATMENT.

PMID- 16590212
TI  - THE INITIATOR CELL FOR SLIME MOLD AGGREGATION.

PMID- 16590213
TI  - THE SONIC FRAGMENTATION OF COLLAGEN MACROMOLECULES.

PMID- 16590214
TI  - INTERACTION PROPERTIES OF SONICALLY FRAGMENTED COLLAGEN MACROMOLECULES.

PMID- 16590215
TI  - THE SOLUTION PROPERTIES AND CONFIGURATIONS OF A POLYAMPHOLYTIC POLYPEPTIDE:
      COPOLY-L-LYSINE-L-GLUTAMIC ACID.

PMID- 16590216
TI  - THE PROPERTIES OF SONIC FRAGMENTS OF DEOXYRIBOSE NUCLEIC ACID.

PMID- 16590217
TI  - LABELING OF PROTEINS BY ISOTOPIC AMINO ACID DERIVATIVES.

PMID- 16590218
TI  - THE MECHANISM OF CHEMICAL MUTAGENESIS. I. KINETIC STUDIES ON THE ACTION OF
      TRIETHYLENE MELAMINE (TEM) AND AZASERINE.

PMID- 16590219
TI  - TRIVIALITY OF VECTOR BUNDLES OVER THE AFFINE SPACE K.

PMID- 16590220
TI  - THE RAPID COMPUTING MACHINE AS AN INSTRUMENT IN THE DISCOVERY OF NEW RELATIONS IN
      THE THEORY OF NUMBERS.

PMID- 16590221
TI  - On the Invariance of Openness.

PMID- 16590222
TI  - l-TYPE DOUBLING IN NH(3).

PMID- 16590223
TI  - ACETATE AS A CALCIUM-SPARING FACTOR IN NITROGEN FIXATION BY AZOTOBACTER
      VINELANDII.

PMID- 16590224
TI  - CELLULAR PROLIFERATION IN THE MOUSE AS REVEALED BY AUTORADIOGRAPHY WITH TRITIATED
      THYMIDINE.

PMID- 16590225
TI  - DIFFERENCE IN ELECTRIC POTENTIAL ACROSS THE PLACENTA OF GOATS.

PMID- 16590226
TI  - A THEOREM ON FORCE-FREE MAGNETIC FIELDS.

PMID- 16590227
TI  - THE EFFECTS OF HYDROXYLAMINE ON THE CO(2) FIXATION PATTERN DURING PHOTOSYNTHESIS.

PMID- 16590229
TI  - VITAMIN K, AN ESSENTIAL FACTOR FOR THE PHOTOCHEMICAL ACTIVITY OF ISOLATED
      CHLOROPLASTS.

PMID- 16590228
TI  - PROTEIN BIOSYNTHESIS BY A CELL-FREE BACTERIAL SYSTEM.

PMID- 16590230
TI  - IONIZATION OF INDIVIDUAL GROUPS IN DIBASIC ACIDS, WITH APPLICATION TO THE AMINO
      AND HYDROXYL GROUPS OF TYROSINE.

PMID- 16590231
TI  - PTERIDINES IN PHOTOSYNTHESIS-AN ARTIFACT OF PAPER CHROMATOGRAPHY.

PMID- 16590232
TI  - ON THE EMISSION OF TRYPTOPHAN.

PMID- 16590233
TI  - ON DISSOCIATION AND RECOMBINATION OF HUMAN ADULT HEMOGLOBINS A, S, AND C.

PMID- 16590234
TI  - EFFECT OF AGE ON THE ENZYME ACTIVITY IN ERYTHROCYTES.

PMID- 16590235
TI  - SPONTANEOUS NUCLEATION IN SUPERSATURATED VAPORS.

PMID- 16590236
TI  - STUDIES ON THE EXCITED STATES OF PROTEINS.

PMID- 16590237
TI  - WALL THICKENING IN SIEVE ELEMENTS.

PMID- 16590238
TI  - INFLUENCE OF THE NUCLEOLUS ON MITOSIS AS REVEALED BY ULTRAVIOLET MICROBEAM
      IRRADIATION.

PMID- 16590239
TI  - THE IMMUNE STATUS OF LONG-TERM SURVIVORS OF LETHALLY X-IRRADIATED MICE PROTECTED
      WITH ISOLOGOUS, HOMOLOGOUS, OR HETEROLOGOUS BONE MARROW.

PMID- 16590240
TI  - GENETIC STUDIES OF IRRADIATED NATURAL POPULATIONS OF DROSOPHILA. II. 1957 TESTS.

PMID- 16590241
TI  - A NEW PROOF OF THE STRONG MARKOV THEOREM OF CHUNG.

PMID- 16590242
TI  - DYNAMIC PROGRAMMING, SUCCESSIVE APPROXIMATIONS, AND MONOTONE CONVERGENCE.

PMID- 16590243
TI  - ON THE THEOREM OF BERTINI FOR LOCAL DOMAINS.

PMID- 16590244
TI  - THE STRUCTURE OF PRIME RINGS WITH MAXIMUM CONDITIONS.

PMID- 16590246
TI  - A FORMULA FOR THE MULTIPLICITY OF A WEIGHT.

PMID- 16590245
TI  - ON THE STRUCTURE OF COMPACT RIEMANNIAN MANIFOLDS.

PMID- 16590247
TI  - TRANSDUCTION BY BACTERIOPHAGE P1: ABNORMAL PHAGE FUNCTION OF THE TRANSDUCING
      PARTICLES.

PMID- 16590248
TI  - THE FUNCTION OF EXTRACELLULAR ENZYMES OF DUTCH ELM DISEASE PATHOGEN.

PMID- 16590249
TI  - NOMENCLATURE OF THE ACTINOMYCINS.

PMID- 16590250
TI  - ON THE NATURE OF FREE RADICALS DETECTED BY PARAMAGNETIC RESONANCE IN BIOLOGICAL
      SUBSTANCES.

PMID- 16590251
TI  - THE RELATION BETWEEN LONGEVITY AND OBESITY IN HUMAN BEINGS.

PMID- 16590252
TI  - INTERRACIAL HYBRIDIZATION AND BREAKDOWN OF COADAPTED GENE COMPLEXES IN DROSOPHILA
      PAULISTORUM AND DROSOPHILA WILLISTONI.

PMID- 16590253
TI  - ENZYMATIC SYNTHESIS OF DEOXYRIBONUCLEIC ACID. III. THE INCORPORATION OF
      PYRIMIDINE AND PURINE ANALOGUES INTO DEOXYRIBONUCLEIC ACID.

PMID- 16590254
TI  - ENZYMATIC SYNTHESIS OF DEOXYRIBONUCLEIC ACID. IV. LINKAGE OF SINGLE
      DEOXYNUCLEOTIDES TO THE DEOXYNUCLEOSIDE ENDS OF DEOXYRIBONUCLEIC ACID.

PMID- 16590255
TI  - VITAMIN A DEFICIENCY AND NIGHT BLINDNESS.

PMID- 16590256
TI  - MOLECULAR INTERACTION OF ISOALLOXAZINE DERIVATIVES.

PMID- 16590257
TI  - PRODUCTION, REPRODUCTION, AND REVERSION OF PROTOPLAST-LIKE STRUCTURES IN THE
      OSMOTIC STRAIN OF NEUROSPORA CRASSA.

PMID- 16590258
TI  - THE REPLICATION OF DNA IN ESCHERICHIA COLI.

PMID- 16590259
TI  - SIGNIFICANT STRUCTURES IN THE LIQUID STATE. I.

PMID- 16590260
TI  - OCCURRENCE OF CHROMOSOMAL ABERRATIONS IN PRE-SPERMATOCYTIC CELLS OF IRRADIATED
      MALE MICE.

PMID- 16590261
TI  - SPACES FOR WHICH THE RICCI SCALAR R IS EQUAL TO ZERO.

PMID- 16590262
TI  - ON THE OPERATIONAL CALCULUS WITH DIFFERENTIABLE FUNCTIONS.

PMID- 16590263
TI  - CYTOLOGICAL AND CYTOCHEMICAL CHANGES IN LIVERS OF WHITE MICE FOLLOWING
      INTRAPERITONEAL INJECTIONS OF DNA PREPARATIONS FROM BREAST CANCERS OF AGOUTI C3H
      MICE.

PMID- 16590264
TI  - A MECHANISM OF CELLULAR THERMOGENESIS IN COLD-ADAPTATION.

PMID- 16590266
TI  - NATIONAL ACADEMY OF SCIENCES: July 1, 1958.

PMID- 16590265
TI  - EPIGENETIC CONTROL SYSTEMS.

PMID- 16590267
TI  - ENZYMATIC FORMATION OF ADENYL TRYPTOPHAN: ISOLATION AND IDENTIFICATION.

PMID- 16590268
TI  - A PSEUDOVECTOR NUCLEAR HYPERFINE INTERACTION.

PMID- 16590269
TI  - ON THE NATURE OF THE GARNET LOCUS IN DROSOPHILA MELANOGASTER.

PMID- 16590270
TI  - ACTION OF RADIATION ON MAMMALIAN CELLS III. RELATIONSHIP BETWEEN REPRODUCTIVE
      DEATH AND INDUCTION OF CHROMOSOME ANOMALIES BY X-IRRADIATION OF EUPLOID HUMAN
      CELLS IN VITRO.

PMID- 16590271
TI  - SEISMIC SURFACE WAVES AT PALISADES FROM EXPLOSIONS IN NEVADA AND THE MARSHALL
      ISLANDS.

PMID- 16590272
TI  - SURFACE OF GIVEN SPACE-CURVE BOUNDARY.

PMID- 16590273
TI  - NOTE ON A CLASS OF DIFFUSION EQUATIONS.

PMID- 16590274
TI  - ON THE PURITY OF THE BRANCH LOCUS OF ALGEBRAIC FUNCTIONS.

PMID- 16590275
TI  - REMARKS ON A PAPER OF ZARISKI ON THE PURITY OF BRANCH-LOCI.

PMID- 16590276
TI  - RADIOACTIVE FALLOUT.

PMID- 16590277
TI  - THE HUMAN ELECTROHYSTEROGRAM: WAVE FORMS AND IMPLICATIONS.

PMID- 16590279
TI  - ON HYDROMAGNETIC EQUILIBRIUM.

PMID- 16590278
TI  - ACTION OF INSECT NEUROSECRETION UPON CENTRAL NERVOUS SYSTEM IN VITRO AND UPON
      BEHAVIOR.

PMID- 16590280
TI  - ON THE EQUILIBRIUM CONFIGURATIONS OF AN INCOMPRESSIBLE FLUID WITH AXISYMMETRIC
      MOTIONS AND MAGNETIC FIELDS.

PMID- 16590281
TI  - THIOLATION OF PROTEINS.

PMID- 16590282
TI  - THE INTERPRETATION OF BACTERIAL TRANSFORMATION DATA.

PMID- 16590283
TI  - FREE RADICAL FORMATION IN RIBOFLAVIN COMPLEXES.

PMID- 16590285
TI  - ISOLATION OF ADENOSINE AMINO ACID ESTERS FROM A RIBONUCLEASE DIGEST OF SOLUBLE,
      LIVER RIBONUCLEIC ACID.

PMID- 16590284
TI  - ON A COENZYMATIC FUNCTION OF ESTRADIOL-17beta.

PMID- 16590286
TI  - THE GENETIC STRUCTURE OF THE INCOMPATIBILITY FACTORS IN SCHIZOPHYLLIUM COMMUNE.

PMID- 16590288
TI  - FUNCTIONAL EQUATIONS IN THE THEORY OF DYNAMIC PROGRAMMING. IX: VARIATIONAL
      ANALYSIS, ANALYTIC CONTINUATION, AND IMBEDDING OF OPERATORS.

PMID- 16590289
TI  - ON THE SEMIRADICAL OF A SEMIRING.

PMID- 16590287
TI  - RADIATION-INDUCED MUTATION RATES IN FEMALE MICE.

PMID- 16590290
TI  - THE STRONG MINKOWSKI FARKAS-WEYL THEOREM FOR VECTOR SPACES OVER ORDERED FIELDS.

PMID- 16590291
TI  - SUPPLEMENT TO A PAPER ENTITLED "A VON STERNECK ARITHMETICAL FUNCTION AND
      RESTRICTED PARTITIONS WITH RESPECT TO A MODULUS".

PMID- 16590292
TI  - ON THE NATURE OF THE SELECTIVE EFFECTS OF DEOXYRIBONUCLEIC ACID DIGESTS UPON
      PNEUMOCOCCI OF DIFFERENT VIRULENCE.

PMID- 16590293
TI  - EFFECTS OF REDUCED OXYGEN TENSION ON GROWTH RESPONSES OF METHIONINE AND VITAMIN
      B(12) STIMULATED MUTANTS OF COLIFORM BACTERIA.

PMID- 16590294
TI  - ON THE DIFFUSE REFLECTION OF A PENCIL OF RADIATION BY A PLANE-PARALLEL
      ATMOSPHERE.

PMID- 16590295
TI  - REMARKS ON THE LONG-WAVE-LENGTH LIMITS OF PHOTOSYNTHESIS AND CHLOROPHYLL
      FLUORESCENCE.

PMID- 16590296
TI  - CRYSTAL STRUCTURE AND INFORMATION THEORY.

PMID- 16590297
TI  - ON THE EUCLIDEAN STRUCTURE OF RELATIVISTIC FIELD THEORY.

PMID- 16590299
TI  - TETRAPOD EXTINCTIONS AT THE END OF THE TRIASSIC PERIOD.

PMID- 16590298
TI  - ON THE SIGNIFICANCE OF TRANSIENTS IN DAILY RHYTHMS.

PMID- 16590300
TI  - THE MODE OF ACTION OF 5-FLUOROURACIL AND ITS DERIVATIVES.

PMID- 16590301
TI  - CREVICE STRUCTURES IN HEMOPROTEIN REACTIONS.

PMID- 16590302
TI  - THE SYNTHESIS OF HEMOGLOBIN IN A CELL-FREE SYSTEM.

PMID- 16590303
TI  - DELAYED LIGHT EMISSION IN GREEN PLANT MATERIALS: TEMPERATURE-DEPENDENCE AND
      QUANTUM YIELD.

PMID- 16590304
TI  - THE BIOSYNTHESIS OF ISOLEUCINE AND VALINE IN NEUROSPORA CRASSA.

PMID- 16590305
TI  - THE PRESENCE OF A(2) ERYTHROCYTES IN A(1) BLOOD.

PMID- 16590306
TI  - GENERATING FUNCTIONS AND THE SEMIGROUP THEORY OF BRANCHING MARKOV PROCESSES.

PMID- 16590307
TI  - THE WORD PROBLEM.

PMID- 16590308
TI  - NON-ADDITIVE FUNCTORS, THEIR DERIVED FUNCTORS, AND THE SUSPENSION HOMOMORPHISM.

PMID- 16590309
TI  - DIFFERENTIABLE MAPPINGS IN THE SCHOENFLIES PROBLEM.

PMID- 16590310
TI  - TRANSFORMATION OF BIOCHEMICALLY DEFICIENT STRAINS OF BACILLUS SUBTILIS BY
      DEOXYRIBONUCLEATE.

PMID- 16590311
TI  - THE APPLICATION OF THE FICK PRINCIPLE TO THE MEASUREMENT OF PULMONARY BLOOD FLOW.

PMID- 16590312
TI  - COCHLEAR POTENTIALS IN THE CAT IN RESPONSE TO HIGH-FREQUENCY SOUNDS.

PMID- 16590313
TI  - SOME EFFECTS OF SUBSTITUTING THE DEOXYRIBONUCLEIC ACID OF ISOLATED NUCLEI WITH
      OTHER POLYELECTROLYTES.

PMID- 16590314
TI  - A NEW WAY FOR THE SYNTHESIS OF 3-AMINO SUGARS.

PMID- 16590315
TI  - THE ENZYMATIC SYNTHESIS OF FATTY ACIDS BY ALDOL CONDENSATION.

PMID- 16590316
TI  - PHOSPHORYLATED INTERMEDIATES IN THE SYNTHESIS OF SQUALENE.

PMID- 16590317
TI  - A COENZYME CONTAINING PSEUDOVITAMIN B(12).

PMID- 16590318
TI  - ON THE REGULATION OF FATTY ACID BIOSYNTHESIS BY LIPOGENIN.

PMID- 16590319
TI  - ELECTRON-SPIN RESONANCE STUDIES OF FREE-RADICAL INTERMEDIATES IN OXIDATION
      REDUCTION ENZYME SYSTEMS.

PMID- 16590320
TI  - LIGHT-INDUCED FREE RADICALS IN FMN AND FLAVOPROTEIN ENZYMES.

PMID- 16590321
TI  - LINEAR ANALYSIS OF TOBACCO MOSAIC VIRUS.

PMID- 16590322
TI  - A SYNTHESIS OF RIBOTHYMIDINE-5'-PYROPHOSPHATE AND ITS CONVERSION TO
      POLYRIBOTHYMIDYLIC ACID.

PMID- 16590323
TI  - PARAMAGNETIC RESONANCE STUDY OF IRRADIATION DAMAGE IN CRYSTALLINE CARBOHYDRATES.

PMID- 16590324
TI  - INCREASE IN FITNESS IN EXPERIMENTAL POPULATIONS RESULTING FROM HETEROSIS.

PMID- 16590325
TI  - DISSOCIATION OF RUBIDIUM UPTAKE BY NEUROSPORA CRASSA INTO ENTRY AND BINDING
      PHASES.

PMID- 16590326
TI  - THE THERMAL CONDUCTIVITY OF CARBON DIOXIDE IN THE REGION OF THE CRITICAL POINT.

PMID- 16590327
TI  - PROTEIN BIOSYNTHESIS BY A CELL-FREE BACTERIAL SYSTEM. II. FURTHER STUDIES ON THE
      AMINO ACID INCORPORATION ENZYME.

PMID- 16590328
TI  - ON THE SEPARATION OF THE TRYPTOPHAN SYNTHETASE OF ESCHERICHIA COLI INTO TWO
      PROTEIN COMPONENTS.

PMID- 16590329
TI  - DORMANCY OF BACTERIAL ENDOSPORES: REGULATION OF ELECTRON TRANSPORT BY DIPICOLINIC
      ACID.

PMID- 16590330
TI  - OBSERVATIONS ON THE FUNCTION OF PYRIDOXAL-5-PHOSPHATE IN PHOSPHORYLASE.

PMID- 16590331
TI  - ENZYMATIC SYNTHESIS OF DEOXYRIBONUCLEIC ACID. V. CHEMICAL COMPOSITION OF
      ENZYMATICALLY SYNTHESIZED DEOXYRIBONUCLEIC ACID.

PMID- 16590332
TI  - ELECTRON-DONOR AND -ACCEPTOR PROPERTIES OF BIOLOGICALLY IMPORTANT PURINES,
      PYRIMIDINES, PTERIDINES, FLAVINS, AND AROMATIC AMINO ACIDS.

PMID- 16590334
TI  - SUCROSE AND GROWTH OF EXCISED ROOTS OF AN INBRED ZEA MAYS.

PMID- 16590335
TI  - THE VISCOSITY OF HIGH POLYMERS-THE RANDOM WALK OF A GROUP OF CONNECTED SEGMENTS.

PMID- 16590333
TI  - SEROTONIN RECEPTORS. I. EXTRACTION AND ASSAY OF A SUBSTANCE WHICH RENDERS
      SEROTONIN FAT-SOLUBLE.

PMID- 16590337
TI  - THE SOMATIC CHOMOSOMES OF MAN.

PMID- 16590336
TI  - BIOLOGICAL DAMAGE IN DEVELOPING GERM CELLS OF DROSOPHILA VIRILIS IN OXYGEN AND
      NITROGEN WITH 14-MEV NEUTRONS.

PMID- 16590338
TI  - COMPLEMENTATION AT THE AD-4 LOCUS IN NEUROSPORA CRASSA.

PMID- 16590339
TI  - COHOMOLOGY THEORY OF VARIETIES OVER RINGS.

PMID- 16590340
TI  - ON THE FOUNDATIONS OF THE THEORY OF DISTRIBUTIONS.

PMID- 16590341
TI  - ON THE SPECTRAL THEORY OF SINGULAR INTEGRAL OPERATORS.

PMID- 16590342
TI  - INDIVIDUAL DIFFERENCES IN SUSCEPTIBILITY TO HYPNOSIS.

PMID- 16590343
TI  - DIRECT EVIDENCE FOR THE TRANSFER OF MATERIALS FROM SYMBIOTIC ALGAE TO THE TISSUES
      OF A COELENTERATE.

PMID- 16590344
TI  - THYMUS RIBONUCLEIC ACID AND EMBRYONIC DIFFERENTIATION.

PMID- 16590345
TI  - CARTILAGE FORMATION IN SOMITE GRAFTS OF CHICK BLASTODERM.

PMID- 16590346
TI  - A MITOCHONDRIAL FACTOR PRODUCING "LOOSE-COUPLING" OF RESPIRATION.

PMID- 16590347
TI  - DISSOCIATION OF HUMAN CARBONMONOXYHEMOGLOBIN AT HIGH pH.

PMID- 16590348
TI  - RADIATION INDUCED REVERSE MUTATIONS IN DROSOPHILA MELANOGASTER.

PMID- 16590349
TI  - DEPENDENCE OF MUTATION FREQUENCY ON RADIATION DOSE RATE IN FEMALE MICE.

PMID- 16590351
TI  - ON THE NATURE OF THE AGING PROCESS.

PMID- 16590350
TI  - MODIFICATION OF IRRADIATION EFFECTS IN THE PIGEON, COLUMBA LIVIA. I. EFFECTS OF
      HOMOLOGOUS AND HETEROLOGOUS BONE MARROW TRANSPLANTS.

PMID- 16590352
TI  - ON IDENTICAL VANISHING OF HOLOMORPHIC FUNCTIONS IN SEVERAL COMPLEX VARIABLES.

PMID- 16590354
TI  - LINE-ELEMENT FIELDS ON THE TORUS.

PMID- 16590353
TI  - LINEAR AND ALGEBRAIC DEPENDENCE OF FUNCTIONS ON COMPACT COMPLEX SPACES WITH
      SINGULARITIES.

PMID- 16590355
TI  - ON A PROBLEM OF MAZURKIEWICZ CONCERNING THE BOUNDARY OF A COVERING SURFACE.

PMID- 16590356
TI  - THE EFFECTS OF STRONTIUM-90 ON MICE.

PMID- 16590358
TI  - GRAVITATIONAL PROPERTIES OF ANTIMATTER.

PMID- 16590357
TI  - GLYCOGEN SYNTHESIS FROM GLUCOSE, GLUCOSE-6-PHOSPHATE, AND URIDINE DIPHOSPHATE
      GLUCOSE IN MUSCLE PREPARATIONS.

PMID- 16590359
TI  - SPECIFIC INTRACELLULAR BINDING OF RUBIDIUM BY RAT DIAPHRAGM MUSCLE.

PMID- 16590360
TI  - INTERACTION BETWEEN PTERIDINES AND TRYPTOPHAN.

PMID- 16590361
TI  - THE ELECTRONIC STRUCTURE OF THE RESPIRATORY COENZYMES.

PMID- 16590362
TI  - ON THE SIZE OF GENETIC DETERMINANTS IN PNEUMOCOCCUS AND THE NATURE OF THE
      VARIABLES INVOLVED IN TRANSFORMATION.

PMID- 16590363
TI  - SIZE OF PORES AND THEIR CONTENTS IN SIEVE ELEMENTS OF DICOTYLEDONS.

PMID- 16590365
TI  - A THEOREM ON ZERO-FIELD SPLITTINGS.

PMID- 16590364
TI  - THE GENERATION OF LATENT-ION-TRANSPORT CAPACITY.

PMID- 16590366
TI  - ON THE ASYMMETRICAL DISSOCIATION OF HUMAN HEMOGLOBIN.

PMID- 16590367
TI  - EFFECT OF ELECTRIC FIELD ON EQUILIBRIUM SEDIMENTATION OF MACROMOLECULES IN A
      DENSITY GRADIENT OF CESIUM CHLORIDE.

PMID- 16590368
TI  - THE MUTATION RATE IN DROSOPHILA AFTER HIGH DOSES OF GAMMA RADIATION.

PMID- 16590369
TI  - ON A MECHANISM OF SUPPRESSOR GENE REGULATION OF TRYPTOPHAN SYNTHETASE ACTIVITY IN
      NEUROSPORA CRASSA.

PMID- 16590370
TI  - GENETIC ALTERATION OF PYRROLINE-5-CARBOXYLATE REDUCTASE IN NEUROSPORA CRASSA.

PMID- 16590371
TI  - INDUCED ELECTROMAGNETIC FIELDS IN THE EARTH.

PMID- 16590372
TI  - DIRICHLET SPACES.

PMID- 16590373
TI  - A RELATIVIZED FATOU THEOREM.

PMID- 16590374
TI  - A THEOREM ON CONVEX BODIES AND APPLICATIONS TO BANACH SPACES.

PMID- 16590375
TI  - SPACES FOR WHICH THE RICCI SCALAR R IS EQUAL TO ZERO. II.

PMID- 16590376
TI  - ON INEQUALITIES OF SZEGO AND BELLMAN.

PMID- 16590377
TI  - THE APPLICATION OF A FIXED-POINT THEOREM TO A VARIETY OF NONLINEAR STABILITY
      PROBLEMS.

PMID- 16590378
TI  - CROSS-REACTIONS OF STREPTOCOCCAL A AND V CARBOHYDRATES IN TYPE II
      ANTIPNEUMOCOCCAL HORSE SERA.

PMID- 16590380
TI  - BONE DOSES FROM STRONTIUM-90.

PMID- 16590379
TI  - GLUTATHIONE AND SULFUR OXIDATION BY THIOBACILLUS THIOOXIDANS.

PMID- 16590381
TI  - SET OF CO-ORDINATE SYSTEMS WHICH DIAGONALIZE THE KINETIC ENERGY OF RELATIVE
      MOTION.

PMID- 16590382
TI  - ELECTRON-SPIN RESONANCE STUDIES OF RADIATION DAMAGE TO CERTAIN LIPIDS, HORMONES,
      AND VITAMINS.

PMID- 16590383
TI  - ELECTRON-SPIN RESONANCE STUDIES OF RADIATION DAMAGE TO THE NUCLEIC ACIDS AND
      THEIR CONSTITUENTS.

PMID- 16590384
TI  - THE CHEMICAL NATURE OF THE RNA-AMINO ACID COMPOUND FORMED BY AMINO ACID
      ACTIVATING ENZYMES.

PMID- 16590385
TI  - A PROCEDURE FOR DETECTING CARRIERS OF GALACTOSEMIA.

PMID- 16590386
TI  - THE SEDIMENTATION PROPERTIES OF THE LARGE SUBUNIT OF DNA RELEASED FROM LABELED
      T(4) BACTERIOPHAGE.

PMID- 16590387
TI  - THE PHYSIOLOGY OF ETHYLENE FORMATION IN APPLES.

PMID- 16590389
TI  - EXTENSIVE DEEP SEA SUB-BOTTOM REFLECTIONS IDENTIFIED AS WHITE ASH.

PMID- 16590388
TI  - PHOTOCONTROL OF PLANT DEVELOPMENT BY THE SIMULTANEOUS EXCITATIONS OF TWO
      INTERCONVERTIBLE PIGMENTS.

PMID- 16590390
TI  - SIGNIFICANCE OF THE WORZEL DEEP SEA ASH.

PMID- 16590391
TI  - ON THE NUMBER OF IRREDUCIBLE CHARACTERS OF FINITE GROUPS IN A GIVEN BLOCK.

PMID- 16590392
TI  - ESTIMATES AND EXISTENCE THEOREMS FOR ELLIPTIC BOUNDARY VALUE PROBLEMS.

PMID- 16590393
TI  - ON THE HOMOLOGY AND HOMOTOPY DECOMPOSITION OF CONTINUOUS MAPS.

PMID- 16590395
TI  - EVIDENCE FOR THE SORTING OUT OF CELLS IN THE DEVELOPMENT OF THE CELLULAR SLIME
      MOLDS.

PMID- 16590394
TI  - A CHARACTERIZATION OF BIRTH AND DEATH PROCESSES.

PMID- 16590397
TI  - SOME STATISTICAL OBSERVATIONS ON A COOPERATIVE STUDY OF HUMAN PULMONARY
      PATHOLOGY. II.

PMID- 16590396
TI  - AN INHIBITOR OF VIRAL ACTIVITY APPEARING IN INFECTED CELL CULTURES.

PMID- 16590398
TI  - BROKEN BOTTLENECKS AND THE FUTURE OF MOLECULAR QUANTUM MECHANICS.

PMID- 16590399
TI  - THE HISTORY OF DOUBLE SCATTERING OF ELECTRONS AND EVIDENCE FOR THE POLARIZATION
      OF BETA RAYS.

PMID- 16590400
TI  - SECRETION AND REABSORPTION IN SWEAT GLANDS.

PMID- 16590401
TI  - AVERAGE BEHAVIOR OF SWEAT GLANDS AS INDICATED BY IMPEDANCE CHANGES.

PMID- 16590402
TI  - THE AUDITORY SENSITIVITY OF ORTHOPTERA.

PMID- 16590403
TI  - DROSOPHILA PAULISTORUM, A CLUSTER OF SPECIES IN STATU NASCENDI.

PMID- 16590404
TI  - SECONDARY STRUCTURE IN RIBONUCLEIC ACIDS.

PMID- 16590405
TI  - THE BIOSYNTHESIS OF MEVALONIC ACID.

PMID- 16590406
TI  - BINDING OF AMINO ACIDS TO THE END GROUP OF A SOLUBLE RIBONUCLEIC ACID.

PMID- 16590407
TI  - ON THE ABSORPTION OF HETEROCYCLIC ELECTRON DONORS AND ACCEPTORS.

PMID- 16590409
TI  - ELECTRON MAGNETIC RESONANCE OF CH(COOH)(2).

PMID- 16590408
TI  - ISOLATION AND PROPERTIES OF B(12) COENZYMES CONTAINING BENZIMIDAZOLE OR
      DIMETHYLBENZIMIDAZOLE.

PMID- 16590410
TI  - HIGH-ACCURACY MECHANICAL INTEGRATION BY SHEAR IN VISCOUS LIQUIDS.

PMID- 16590411
TI  - THE DISCRIMINATION OF WILD-TYPE ISOALLELES AT THE WHITE LOCUS OF DROSOPHILA
      MELANOGASTER.

PMID- 16590412
TI  - EXCEPTIONAL INHERITANCE OF A SEX-LINKED GENE IN THE MOUSE EXPLAINED ON THE BASIS
      THAT THE X/O SEX-CHROMOSOME CONSTITUTION IS FEMALE.

PMID- 16590414
TI  - REACTOR CRITICALITY IN TRANSPORT THEORY.

PMID- 16590413
TI  - THE Y-CHROMOSOME AS THE BEARER OF MALE DETERMINING FACTORS IN THE MOUSE.

PMID- 16590415
TI  - A CLASS OF DIOPHANTINE EQUATIONS.

PMID- 16590416
TI  - AUTOMORPHIC FORMS ON A SEMISIMPLE LIE GROUP.

PMID- 16590417
TI  - TIME OPTIMAL CONTROL SYSTEMS.

PMID- 16590418
TI  - FINITE GROUPS WITH FIXED-POINT-FREE AUTOMORPHISMS OF PRIME ORDER.

PMID- 16590419
TI  - PRODUCTION OF STERILITY IN MICE BY DEUTERIUM OXIDE.

PMID- 16590420
TI  - NOTE ON THE LATERAL DENDRITES OF PLANTAR MOTONEURONS.

PMID- 16590421
TI  - TEMPERATURE AND DENDRITIC RESPONSE OF SPINAL MOTONEURONS.

PMID- 16590422
TI  - DECREMENTAL CONDUCTION IN PERIPHERAL NERVE. INTEGRATION OF STIMULI IN THE NEURON.

PMID- 16590423
TI  - COMPARISON OF POPULATION ENERGY FLOW OF A HERBIVOROUS AND A DEPOSIT-FEEDING
      INVERTEBRATE IN A SALT MARSH ECOSYSTEM.

PMID- 16590424
TI  - THE DIFFERENCE BETWEEN SPONTANEOUS AND BASE-ANALOGUE INDUCED MUTATIONS OF PHAGE
      T4.

PMID- 16590425
TI  - SOME EXAMPLES ON n-DIMENSIONAL STRUCTURAL STABILITY.

PMID- 16590426
TI  - COLOR VISION AND THE NATURAL IMAGE PART II.

PMID- 16590427
TI  - ON PHYSICAL HEAT REGULATION AND THE SENSE OF TEMPERATURE IN MAN.

PMID- 16590428
TI  - METABOLIC ACTIVITIES OF SUBCELLULAR PARTICLES FROM AZOTOBACTER VINELANDII.

PMID- 16590429
TI  - DIHYDROTHIOCTYL DEHYDROGENASE-A FLAVOPROTEIN.

PMID- 16590430
TI  - THE ATP-DEPENDENT REDUCTION OF SULFATE WITH HYDROGEN IN EXTRACTS OF DESULFOVIBRIO
      DESULFURICANS.

PMID- 16590431
TI  - MUTATION INDUCTION AND MACROMOLECULAR SYNTHESIS IN BACTERIA.

PMID- 16590432
TI  - TRANSDUCTION BY STAPHYLOCOCCAL BACTERIOPHAGE.

PMID- 16590433
TI  - ABERRANT TETRADS IN SORDARIA FIMICOLA.

PMID- 16590434
TI  - UNIQUE FACTORIZATION IN REGULAR LOCAL RINGS.

PMID- 16590435
TI  - ON THE FALSITY OF EULER'S CONJECTURE ABOUT THE NON-EXISTENCE OF TWO ORTHOGONAL
      LATIN SQUARES OF ORDER 4t + 2.

PMID- 16590436
TI  - WHICH LIE GROUPS ARE HOMOTOPY-ABELIAN?

PMID- 16590437
TI  - A QUANTITATIVE FORMULATION OF SYLVESTER'S LAW OF INERTIA.

PMID- 16590438
TI  - ENERGY ABSORPTION BY CHARGE CARRIERS OF NEGATIVE EFFECTIVE MASS IN CRYSTALS.

PMID- 16590439
TI  - SEX INDUCED WITH ECDYSONE.

PMID- 16590440
TI  - MULTIPLE FORMS OF ENZYMES: TISSUE, ONTOGENETIC, AND SPECIES SPECIFIC PATTERNS.

PMID- 16590441
TI  - INTERACTION BETWEEN FORMALDEHYDE AND TOBACCO MOSAIC VIRUS.

PMID- 16590442
TI  - HYDROMAGNETIC EQUILIBRIUM II. STABILITY IN THE VARIATIONAL FORMULATION.

PMID- 16590443
TI  - ENZYMATIC SYNTHESIS OF DEOXYRIBONUCLEIC ACID. INFLUENCE OF BACTERIOPHAGE T2 ON
      THE SYNTHETIC PATHWAY IN HOST CELLS.

PMID- 16590444
TI  - PURIFIED MUSCLE PROTEINS AND THE WALKING RATE OF ANTS.

PMID- 16590445
TI  - A FUNCTIONAL DISORDER OF MUSCLE ASSOCIATED WITH THE ABSENCE OF PHOSPHORYLASE.

PMID- 16590446
TI  - ACTION SPECTRA FOR THE POSITIVE AND NEGATIVE PHOTOTROPISM OF PHYCOMYCES
      SPORANGIOPHORES.

PMID- 16590447
TI  - THE FUOSS-ONSAGER CONDUCTANCE EQUATION AT HIGH CONCENTRATIONS.

PMID- 16590448
TI  - DEPENDENCE OF THE WALDEN PRODUCT ON DIELECTRIC CONSTANT.

PMID- 16590449
TI  - MECHANISM OF CONTRACTION IN THE MUSCLE FIBER-ATP SYSTEM.

PMID- 16590450
TI  - PARAMUTATION AT THE R LOCUS IN MAIZE PLANTS TRISOMIC FOR CHROMOSOME 10.

PMID- 16590451
TI  - A REGULAR AND CONTINUING CONVERSION-TYPE PHENOMENON AT THE B LOCUS IN MAIZE.

PMID- 16590452
TI  - RECOVERY IN STATIONARY-PHASE PARAMECIA FROM RADIATION EFFECTS LEADING TO
      MUTATION.

PMID- 16590453
TI  - CHROMOSOME BREAKAGE PRODUCED BY TRITIUM-LABELED THYMIDINE IN TRADESCANTIA
      PALUDOSA.

PMID- 16590454
TI  - ENZYME COMPLEMENTATION IN VITRO BETWEEN ADENYLOSUCCINASELESS MUTANTS OF
      NEUROSPORA CRASSA.

PMID- 16590455
TI  - LOWER BOUNDS FOR EIGENVALUES WITH APPLICATION TO THE HELIUM ATOM.

PMID- 16590456
TI  - FUNCTIONAL EQUATIONS AND THETA-FUNCTIONS-I.

PMID- 16590457
TI  - GENERALIZED CONJUGATE AND ANALYTIC FUNCTIONS WITHOUT EXPANSIONS.

PMID- 16590458
TI  - A COVERING HOMOTOPY THEOREM AND THE CLASSIFICATION OF G-SPACES.

PMID- 16590459
TI  - ORTHOGONAL LATIN SQUARES.

PMID- 16590460
TI  - A DEMONSTRATION OF ANTIBODY ACTIVITY ON MICROSOMES.

PMID- 16590461
TI  - ISOLATION AND STUDY OF MUTANTS FROM MAMMALIAN CELLS IN CULTURE.

PMID- 16590462
TI  - ESTIMATION OF MUTATION RATES WITH MAMMALIAN CELLS IN CULTURE.

PMID- 16590463
TI  - AN INFECTIOUS RIBONUCLEIC ACID DERIVED FROM INFLUENZA-INFECTED CELLS.

PMID- 16590464
TI  - ON A SYMMETRY IN WEAK INTERACTIONS.

PMID- 16590465
TI  - CHANGES IN PLASMA 17-HYDROXYCORTICOSTEROIDS ACCOMPANYING SEXUAL MATURATION AND
      SPAWNING OF THE PACIFIC SALMON (ONCORHYNCHUS TSCHAWYTSCHA) AND RAINBOW TROUT
      (SALMO GAIRDNERII).

PMID- 16590466
TI  - THYROID RADIATION DOSES FROM FALLOUT.

PMID- 16590467
TI  - THE ELIMINATION OF DNA FROM SOMA CELLS.

PMID- 16590468
TI  - PARENTAL CONTROL OF POSITION-EFFECT VARIEGATION: I. PARENTAL HETEROCHROMATIN AND
      EXPRESSION OF THE WHITE LOCUS IN COMPOUND-X DROSOPHILA MELANOGASTER.

PMID- 16590469
TI  - THE SOMATIC CHROMOSOMAL CONSTITUTION OF SOME HUMAN SUBJECTS WITH GENETIC DEFECTS.

PMID- 16590470
TI  - THE EFFECTS OF DELETIONS, POINT MUTATIONS, REVERSIONS AND SUPPRESSOR MUTATIONS ON
      THE TWO COMPONENTS OF THE TRYPTOPHAN SYNTHETASE OF ESCHERICHIA COLI.

PMID- 16590471
TI  - ON THE LIMIT OF SOLUTIONS OF DIFFERENTIAL-DIFFERENCE EQUATIONS AS THE RETARDATION
      APPROACHES ZERO.

PMID- 16590472
TI  - THE RICCI PRINCIPAL DIRECTION VECTORS.

PMID- 16590473
TI  - AN EXTENSION OF CERTAIN RESULTS IN FUNCTION THEORY TO A CLASS OF SURFACES.

PMID- 16590474
TI  - THE PROPAGATION OF MULTIPLE VIRUSES IN CHICK KIDNEY CULTURES.

PMID- 16590475
TI  - THE RELATIVE HOMOGENEITY OF MICROBIAL DNA.

PMID- 16590476
TI  - STRAIN SPECIFICITY AND PRODUCTION OF ANTIBIOTIC SUBSTANCES. X. CHARACTERIZATION
      AND CLASSIFICATION OF SPECIES WITHIN THE STREPTOMYCES GRISEUS GROUP.

PMID- 16590477
TI  - COMPENSATIONS IN ELECTRON EXCITATION EFFECTS IN p-p AND p-n SCATTERING.

PMID- 16590478
TI  - A SURVEY OF OUR PRESENT SOURCES OF INFORMATION ON THE CONVERSION CONSTANT,
      A(=lambda(g)/lambda(s)) AND THE ABSOLUTE WAVELENGTHS OF X-RAY EMISSION LINES.

PMID- 16590479
TI  - LASTING AFTER-EFFECTS PRODUCED IN RATS BY SEVERAL COMMONLY USED DRUGS AND
      HORMONES.

PMID- 16590480
TI  - REPRODUCTIVE CYCLES IN AN EQUATORIAL SPARROW.

PMID- 16590481
TI  - NATIONAL ACADEMY OF SCIENCES.

PMID- 16590482
TI  - SUGAR NUCLEOTIDES IN THE INTERCONVERSION OF CARBOHYDRATES IN HIGHER PLANTS.

PMID- 16590483
TI  - EFFECT OF SOLVENTS AND OF TEMPERATURE ON THE OPTICAL ROTATORY PROPERTIES OF
      PEPSIN.

PMID- 16590484
TI  - UNITY IN THE SPECIFICITY OF ENZYME AND ANTIBODY INDUCTION BY THE SAME DETERMINANT
      GROUPS.

PMID- 16590485
TI  - AN EARLY PHASE IN THE BACTERICIDAL ACTION OF 5-FLUOROURACIL ON E. COLI K(12).
      OSMOTIC IMBALANCE.

PMID- 16590486
TI  - A DEMONSTRATION OF THE RECOVERY OF THE CROWN-GALL TUMOR CELL WITH THE USE OF
      COMPLEX TUMORS OF SINGLE-CELL ORIGIN.

PMID- 16590487
TI  - EQUILIBRIUM SEDIMENTATION IN A DENSITY GRADIENT OF MATERIALS HAVING A CONTINUOUS
      DISTRIBUTION OF EFFECTIVE DENSITIES.

PMID- 16590488
TI  - AGGREGATION OF DYES BOUND TO POLYANIONS.

PMID- 16590489
TI  - SEARCH FOR UNSTABLE CO(2) FIXATION PRODUCTS IN ALGAE USING LOW TEMPERATURE LIQUID
      SCINTILLATORS.

PMID- 16590490
TI  - RADIOACTIVE FALLOUT PARTICULARLY FROM THE RUSSIAN OCTOBER SERIES.

PMID- 16590491
TI  - GENETIC RECOMBINATION BETWEEN ESCHERICHIA COLI AND SALMONELLA TYPHIMURIUM.

PMID- 16590492
TI  - ROLE OF EPISTASIS AND OVERDOMINANCE IN STABILITY OF EQUILIBRIA WITH SELECTION.

PMID- 16590493
TI  - STABLE EQUILIBRIA FOR THE OPTIMUM MODEL.

PMID- 16590494
TI  - PLEIOTROPY AND COMPETITION AT THE VERMILION LOCUS IN DROSOPHILA MELANOGASTER.

PMID- 16590496
TI  - ON CHARGE TRANSFER COMPLEXES BETWEEN SUBSTANCES OF BIOCHEMICAL INTEREST.

PMID- 16590495
TI  - INCORPORATION OF H CYTIDINE AND H THYMIDINE INTO GIANT CHROMOSOMES OF DROSOPHILA
      DURING PUFF FORMATION.

PMID- 16590497
TI  - ON THE ELECTRON PARAMAGNETIC RESONANCE OF ADENOSINE TRIPHOSPHATE.

PMID- 16590498
TI  - ENZYMES IN A GLYCOGEN STORAGE MYOPATHY.

PMID- 16590499
TI  - GLYCOGEN SYNTHESIS IN MUSCLE LACKING PHOSPHORYLASE.

PMID- 16590500
TI  - HYDROXYMETHYLDEOXYCYTIDYLATE KINASE FORMATION AFTER BACTERIOPHAGE INFECTION OF
      ESCHERICHIA COLI.

PMID- 16590501
TI  - THE ROLE OF ORGANIC SUBSTRATES IN BACTERIAL PHOTOSYNTHESIS.

PMID- 16590502
TI  - SUBCELLULAR PARTICULATE SYSTEMS AND THE PHOTOCHEMICAL APPARATUS OF RHODOSPIRILLUM
      RUBRUM.

PMID- 16590503
TI  - A CRITERION FOR ORBITAL HYBRIDIZATION AND CHARGE DISTRIBUTION IN CHEMICAL BONDS.

PMID- 16590504
TI  - THE EFFECTS OF SPREADING TECHNIQUE AND PURITY OF SAMPLE ON THE EVAPORATION
      RESISTANCE OF MONOLAYERS.

PMID- 16590505
TI  - THE FORMATION OF A NEW ENZYMATICALLY ACTIVE PROTEIN AS A RESULT OF SUPPRESSION.

PMID- 16590507
TI  - PARTITIONS IN HOMOGENEOUS, FINITE ABELIAN GROUPS.

PMID- 16590506
TI  - A MATHEMATICAL THEORY OF ADAPTIVE CONTROL PROCESSES.

PMID- 16590508
TI  - ON ENTIRE SOLUTIONS OF NONLINEAR DIFFERENTIAL EQUATIONS.

PMID- 16590509
TI  - CRITICAL SIGNIFICANCE OF BREAST STRUCTURE IN THE INDUCTION OF MAMMARY CANCER IN
      THE RAT.

PMID- 16590510
TI  - MICROSCOPIC TESTS OF SYMMETRY PRINCIPLES.

PMID- 16590511
TI  - MINIATURIZATION OF THE ELECTROMAGNETIC BLOOD FLOW METER AND ITS USE FOR THE
      RECORDING OF CIRCULATORY RESPONSES OF CONSCIOUS ANIMALS TO SENSORY STIMULI.

PMID- 16590512
TI  - CONTRASTS IN THE METABOLIC STABILITY OF DIFFERENT NUCLEOTIDES IN THE RIBONUCLEIC
      ACIDS OF ISOLATED NUCLEI.

PMID- 16590513
TI  - LINKED FUNCTIONS IN HEME SYSTEMS: OXIDATION-REDUCTION POTENTIALS AND ABSORPTION
      SPECTRA OF A HEME PEPTIDE OBTAINED UPON PEPTIC HYDROLYSIS OF CYTOCHROME C.

PMID- 16590514
TI  - AMINO ACID SEQUENCE SELECTION IN PROTEIN SYNTHESIS.

PMID- 16590515
TI  - PYRIDOXAL KINASE OF HUMAN BRAIN AND ITS INHIBITION BY HYDRAZINE DERIVATIVES.

PMID- 16590516
TI  - INHIBITION OF IODIDE OXIDATION BY THYROXINE AND OTHER ANTIOXIDANTS.

PMID- 16590517
TI  - ANALYSIS OF CONDUCTANCE DATA FOR 1-1 IONOPHORES.

PMID- 16590518
TI  - SOME ASPECTS OF PHOSPHATE CHEMISTRY.

PMID- 16590519
TI  - GENETIC RADIATION DAMAGE REVERSAL BY NITROGEN, METHANE, AND ARGON.

PMID- 16590520
TI  - STUDIES ON NORMAL AND GENETICALLY ALTERED TRYPTOPHAN SYNTHETASE FROM NEUROSPORA
      CRASSA.

PMID- 16590522
TI  - ON THE SPECTRAL THEORY OF STRONGLY ELLIPTIC DIFFERENTIAL OPERATORS.

PMID- 16590521
TI  - MEIOTIC DRIVE IN NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER. II. GENETIC
      VARIATION AT THE SEGREGATION-DISTORTER LOCUS.

PMID- 16590523
TI  - MAPPING NORMS.

PMID- 16590524
TI  - SYNTHESIS OF NASCENT PROTEIN BY RIBOSOMES IN ESCHERICHIA COLI.

PMID- 16590525
TI  - THE LOWER RANGE OF THE COCHLEAR POTENTIALS.

PMID- 16590526
TI  - COORDINATE REPRESSION OF THE SYNTHESIS OF FOUR HISTIDINE BIOSYNTHETIC ENZYMES BY
      HISTIDINE.

PMID- 16590527
TI  - AMINO ACID ACTIVATION AND TRANSFER TO RIBONUCLEIC ACIDS IN THE CELL NUCLEUS.

PMID- 16590528
TI  - A GENERAL METHOD FOR THE LABELING OF THE ACTIVE SITE OF ANTIBODIES AND ENZYMES.

PMID- 16590529
TI  - ON THE METABOLIC BREAKDOWN OF HEMOGLOBIN AND THE ELECTRONIC STRUCTURE OF THE BILE
      PIGMENTS.

PMID- 16590530
TI  - A STATISTICAL ANALYSIS OF DEOXYRIBONUCLEIC ACID DISTRIBUTION IN DENSITY GRADIENT
      CENTRIFUGATION.

PMID- 16590531
TI  - THE BIOSYNTHESIS OF p-AMINOBENZOIC ACID.

PMID- 16590532
TI  - GLUCOSE INHIBITION AND THE DIAUXIE PHENOMENON.

PMID- 16590533
TI  - MUTATIONAL HETEROZYGOTES IN BACTERIOPHAGES.

PMID- 16590534
TI  - NON-RANDOM GENE DISTRIBUTION AMONG TOMATO CHROMOSOMES.

PMID- 16590535
TI  - ON THE RADICAL OF A POSITIVE SEMIRING.

PMID- 16590536
TI  - ON SUBMANIFOLDS OF CERTAIN FUNCTION SPACES.

PMID- 16590537
TI  - EXTERIOR DIFFERENTIAL SYSTEMS AND ELLIPTIC EQUATIONS.

PMID- 16590538
TI  - POLYNOMIALS OF BEST APPROXIMATION ON AN INTERVAL.

PMID- 16590539
TI  - NOTE ON INVARIANCE OF DEGREE OF POLYNOMIAL AND TRIGONOMETRIC APPROXIMATION UNDER
      CHANGE OF INDEPENDENT VARIABLE.

PMID- 16590540
TI  - BIOASSAY OF ORGANIC MICRONUTRIENTS IN THE SEA.

PMID- 16590542
TI  - ON INEQUALITIES OF SZEGO AND BELLMAN.

PMID- 16590541
TI  - THE ALGEBRA OF MICROSCOPIC MEASUREMENT.

PMID- 16590543
TI  - ON THE SIMILARITY OF CHAIN LENGTH OF NUCLEIC ACIDS.

PMID- 16590544
TI  - THE EFFECT OF HYDRODYNAMIC SHEAR ON THE DEOXYRIBONUCLEIC ACID FROM T(2) AND T(4)
      BACTERIOPHAGES.

PMID- 16590545
TI  - THE PHOTOCHEMICAL OXIDATION OF DPNH WITH RIBOFLAVIN PHOSPHATE.

PMID- 16590546
TI  - ELEMENTS OF A GENERAL THEORY OF ENZYMATIC HYDROLYSIS.

PMID- 16590547
TI  - A SULFOLIPID IN PLANTS.

PMID- 16590548
TI  - AN EFFECT OF AUXINS ON THE HEAT COAGULABILITY OF THE PROTEINS OF GROWING PLANT
      CELLS.

PMID- 16590549
TI  - ANOMALOUS OPTICAL ROTATORY DISPERSION OF DYE: POLYPEPTIDE COMPLEXES.

PMID- 16590550
TI  - SIGNIFICANT STRUCTURES IN LIQUIDS. II.

PMID- 16590551
TI  - HYPERFINE ABSORPTION SPECTRUM OF CH(COOH)(2).

PMID- 16590552
TI  - DETERMINATION OF THE PARAMETERS FOR HELIX FORMATION IN POLY-gamma-BENZYL-L
      GLUTAMATE.

PMID- 16590553
TI  - ON THE TOPOLOGY OF THE GENETIC FINE STRUCTURE.

PMID- 16590554
TI  - MUTATION INDUCTION AND EXPRESSION IN BACTERIA.

PMID- 16590556
TI  - CONFORMALLY INVARIANT METRICS ON RIEMANN SURFACES.

PMID- 16590555
TI  - THE RELATIONSHIP OF GENE CONVERSION TO CROSSING OVER IN NEUROSPORA.

PMID- 16590557
TI  - INVARIANT SETS OF STRUCTURALLY STABLE DIFFERENTIAL SYSTEMS.

PMID- 16590558
TI  - ON DISTRIBUTION PROBLEMS INVOLVING THE NUMBERS OF SOLUTIONS OF CERTAIN TRINOMIAL
      CONGRUENCES.

PMID- 16590559
TI  - SPECTROPHOTOMETRIC STUDIES OF THE EFFECTS OF NITROGEN ON SOYBEAN NODULE EXTRACTS.

PMID- 16590560
TI  - THE REACTIVITY OF A NATURALLY OCCURRING QUINONE (Q-255) IN PHOTOCHEMICAL
      REACTIONS OF ISOLATED CHLOROPLASTS.

PMID- 16590561
TI  - DETECTION, ASSAY, AND PRELIMINARY PURIFICATION OF THE PIGMENT CONTROLLING
      PHOTORESPONSIVE DEVELOPMENT OF PLANTS.

PMID- 16590562
TI  - MOLECULAR INTERACTION OF ISOALLOXAZINE DERIVATIVES. II.

PMID- 16590563
TI  - ON BIOCHEMICAL EVOLUTION: LYSINE FORMATION IN HIGHER PLANTS.

PMID- 16590564
TI  - INHIBITION BY PUROMYCIN OF AMINO ACID INCORPORATION INTO PROTEIN.

PMID- 16590566
TI  - MAXIMUM GROWTH RATES OF CHLORELLA IN STEADY-STATE AND IN SYNCHRONIZED CULTURES.

PMID- 16590565
TI  - INHIBITION OF THE ENZYMIC OXIDATION OF DPNH BY STER HORMONES.

PMID- 16590567
TI  - PARAMAGNETIC RESONANCE SPECTRA OF FREE RADICALS TRAPPED ON IRRADIATION OF
      CRYSTALLINE CARBOHYDRATES.

PMID- 16590568
TI  - CHARACTERISTICS OF A HIGH FREQUENCY OF RECOMBINATION (HFR) STRAIN OF SALMONELLA
      TYPHOSA COMPATIBLE WITH SALMONELLA, SHIGELLA, AND ESCHERICHIA SPECIES.

PMID- 16590569
TI  - ON FINITE GROUPS OF EVEN ORDER WHOSE 2-SYLOW GROUP IS A QUATERNION GROUP.

PMID- 16590571
TI  - SOME RESULTS ON DIFFERENTIAL EQUATIONS AND THEIR APPLICATIONS.

PMID- 16590570
TI  - GENERALIZED SPACES OF GENERAL RELATIVITY.

PMID- 16590572
TI  - SPECTRAL REPRESENTATIONS AND UNBOUNDED CONVOLUTION OPERATORS.

PMID- 16590573
TI  - LOWER BOUNDS FOR RISK FUNCTIONS IN ESTIMATION.

PMID- 16590574
TI  - ORBIT SPACES OF ABELIAN p-GROUPS.

PMID- 16590575
TI  - HEREDITARY DEFECTS IN GALACTOSE METABOLISM IN ESCHERICHIA COLI MUTANTS, I.
      DETERMINATION OF ENZYME ACTIVITIES.

PMID- 16590576
TI  - HEREDITARY DEFECTS IN GALACTOSE METABOLISM IN ESCHERICHIA COLI MUTANTS, II.
      GALACTOSE-INDUCED SENSITIVITY.

PMID- 16590577
TI  - THE RELATIONSHIP OF SODIUM, POTASSIUM, AND DEOXYCORTICOSTERONE IN NEUROSPORA
      CRASSA.

PMID- 16590578
TI  - SULFOLIPID FROM VIRULENT TUBERCLE BACILLI.

PMID- 16590579
TI  - ISOLATION OF INFECTIOUS DEOXYRIBONUCLEIC ACID FROM SE POLYOMA-INFECTED TISSUE
      CULTURES.

PMID- 16590580
TI  - DISTRIBUTION AND MOTION OF INTERSTELLAR HYDROGEN IN THE GALACTIC SYSTEM WITH
      PARTICULAR REFERENCE TO THE REGION WITHIN 3 KILOPARSECS OF THE CENTER.

PMID- 16590581
TI  - EFFECTS OF HEATING DRY BACTERIA AND SPORES ON THEIR PHENOTYPE AND GENOTYPE.

PMID- 16590582
TI  - FIELDS OF GEODESICS ISSUING FROM A POINT.

PMID- 16590584
TI  - A SIMPLE PROOF OF THE CUP PRODUCT REDUCTION THEOREM.

PMID- 16590583
TI  - FUNDAMENTAL GROUPS ON A LORENTZ MANIFOLD.

PMID- 16590585
TI  - MECHANICAL GERMINATION OF BACTERIAL SPORES.

PMID- 16590586
TI  - INVARIANT IMBEDDING AND NEUTRON TRANSPORT IN A ROD OF CHANGING LENGTH.

PMID- 16590587
TI  - INTERNATIONAL COOPERATIVE EFFORTS DIRECTED TOWARD OPTICAL IDENTIFICATION OF RADIO
      SOURCES.

PMID- 16590588
TI  - HYDROMAGNETIC WAVES IN A COMPRESSIBLE FLUID CONDUCTOR.

PMID- 16590589
TI  - THE HYDRODYNAMIC STABILITY OF INVISCID FLOW BETWEEN COAXIAL CYLINDERS.

PMID- 16590590
TI  - THE HYDRODYNAMIC STABILITY OF VISCID FLOW BETWEEN COAXIAL CYLINDERS.

PMID- 16590591
TI  - ON THE RELATION BETWEEN REPRODUCTIVE VALUE AND OPTIMAL PREDATION.

PMID- 16590592
TI  - ON THE MECHANISM OF CHLOROPHYLL-CYTOCHROME INTERACTION: THE TEMPERATURE
      INSENSITIVITY OF LIGHT-INDUCED CYTOCHROME OXIDATION IN CHROMATIUM.

PMID- 16590593
TI  - STUDIES ON THE BIOSYNTHESIS OF PRODIGIOSIN IN SERRATIA MARCESCENS.

PMID- 16590594
TI  - THE ROLE OF TRANSCARBOXYLATION IN PROPIONIC ACID FERMENTATION.

PMID- 16590595
TI  - HOW STABLE IS BALANCED POLYMORPHISM?

PMID- 16590596
TI  - THE OCCURRENCE OF PARTIALLY FERTILE TRIPLOID METAFEMALES IN DROSOPHILA
      MELANOGASTER.

PMID- 16590597
TI  - THE BEHAVIOR OF NONHOMOLOGOUS CHROMOSOMAL ELEMENTS INVOLVED IN NONRANDOM
      ASSORTMENT IN DROSOPHILA MELANOGASTER.

PMID- 16590598
TI  - THE EFFECT OF ACRIDINE DYES ON MATING TYPE FACTORS IN ESCHERICHIA COLI.

PMID- 16590599
TI  - EVOLUTION AND PTERIDINE METABOLISM IN THE GENUS DROSOPHILA.

PMID- 16590600
TI  - HYBRIDIZATION BETWEEN LYCOPERSICON ESCULENTUM AND SOLANUM PENNELLII: PHYLOGENETIC
      AND CYTOGENETIC SIGNIFICANCE.

PMID- 16590601
TI  - MITOTIC REPLICATION OF DEOXYRIBONUCLEIC ACID IN CHLAMYDOMONAS REINHARDI.

PMID- 16590602
TI  - GENETIC STRUCTURE OF RECOMBINANT CHROMOSOMES FORMED AFTER MATING IN ESCHERICHIA
      COLI K12.

PMID- 16590603
TI  - SOLAR FEATURES ASSOCIATED WITH ELLERMAN'S "SOLAR HYDROGEN BOMBS".

PMID- 16590604
TI  - STUDIES ON S-RNA SYNTHESIS, I. PURIFICATION AND GENERAL CHARACTERISTICS OF THE
      RNA-ENZYME COMPLEX.

PMID- 16590605
TI  - BIOCHEMICAL AND NUTRITIONAL STUDIES ON THE INDUCTION OF FATTY LIVERS BY DIETARY
      OROTIC ACID.

PMID- 16590606
TI  - THE CHARGE PROFILE OF THE TROPOCOLLAGEN MACROMOLECULE AND THE PACKING ARRANGEMENT
      IN NATIVE-TYPE COLLAGEN FIBRILS.

PMID- 16590607
TI  - THE EFFECTS OF PROTEASES ON THE TROPOCOLLAGEN MACROMOLECULE AND ON ITS
      AGGREGATION PROPERTIES.

PMID- 16590608
TI  - ON THE SITES OF ATTACHMENT AND REACTION OF ALDEHYDE DEHYDROGEN ASES.

PMID- 16590609
TI  - ORGANIC MATTER IN THE ATMOSPHERE, AND ITS POSSIBLE RELATION TO PETROLEUM
      FORMATION.

PMID- 16590610
TI  - NONRANDOM ASSORTMENT IN PRIMARY NONDISJUNCTION IN DROSOPHILA MELANOGASTER.

PMID- 16590611
TI  - THE EFFECT OF POSTTREATMENT WITH OHLORAMPHENICOL VARIOUS ULTRAVIOLET-INDUCED
      MUTATIONS IN ESCHERICHIA COLI.

PMID- 16590612
TI  - TRANSIENT EFFECTS IN THE DISTRIBUTION OF CARBON-14 IN NATURE.

PMID- 16590613
TI  - CARBON-14 PRODUCTION FROM NUCLEAR EXPLOSIONS.

PMID- 16590614
TI  - A NOTE ON THE CONTINUITY OF CHARACTERISTIC EXPONENTS.

PMID- 16590615
TI  - LINEAR DIOPHANTINE INEQUALITIES APPLIED TO GENERALIZED FABER POLYNOMIALS.

PMID- 16590616
TI  - THE STABILITY OF NON-DISSIPATIVE COUETTE FLOW IN HYDROMAGNETICS.

PMID- 16590617
TI  - THE GEOMETRY OF QUANTUM STATES.

PMID- 16590618
TI  - INDIGENOUS ORGANIC MATTER ON THE MOON.

PMID- 16590619
TI  - BIOLOGICAL CONTAMINATION OF THE MOON.

PMID- 16590620
TI  - INTRAMOLECULAR MODELS DEPICTING THE KINETIC IMPORTANCE OF "FIT" IN ENZYMATIC
      CATALYSIS.

PMID- 16590621
TI  - FREE RADICALS IN HEART MUSCLE MITOCHONDRIAL PARTICLES: GENERAL CHARACTERISTICS
      AND LOCALIZATION IN THE ELECTRON TRANSPORT SYSTEM.

PMID- 16590622
TI  - FREE RADICALS IN HEART MUSCLE MITOCHONDRIAL PARTICLES: MECHANISM OF FORMATION.

PMID- 16590623
TI  - THE SUSTAINED GROWTH OF HUMAN AND ANIMAL CELLS IN A PROTEIN-FREE ENVIRONMENT.

PMID- 16590624
TI  - METABOLISM AND MORPHOLOGY OF RIBONUCLEOPROTEIN PARTICLES FROM THE CELL NUCLEUS OF
      LYMPHOCYTES.

PMID- 16590625
TI  - EVIDENCE FOR HELICAL STRUCTURE IN POLYURIDYLIC ACID.

PMID- 16590626
TI  - INHIBITION OF MAMMALIAN GLUCOSE-6-PHOSPHATE DEHYDROGENASE BY STEROIDS.

PMID- 16590627
TI  - STRAND SEPARATION AND SPECIFIC RECOMBINATION IN DEOXYRIBONUCLEIC ACIDS:
      BIOLOGICAL STUDIES.

PMID- 16590628
TI  - STRAND SEPARATION AND SPECIFIC RECOMBINATION IN DEOXYRIBONUCLEIC ACIDS: PHYSICAL
      CHEMICAL STUDIES.

PMID- 16590629
TI  - THE RELATION OF UREA TO THE MOVEMENT OF WATER IN LIVER TISSUE.

PMID- 16590630
TI  - THE INCORPORATION OF LEUCINE-C INTO PROTEIN BY A CELL-FREE PREPARATION FROM MAIZE
      KERNELS.

PMID- 16590631
TI  - REPRESSION OF AN ACETYLORNITHINE PERMEATION SYSTEM.

PMID- 16590632
TI  - THE BALANCE BETWEEN COHERENCE AND VARIATION IN EVOLUTION.

PMID- 16590633
TI  - PARAMAGNETIC DEFECTS IN IRRADIATED KClO(4).

PMID- 16590634
TI  - CONTINUOUS ELECTROPHORETIC FRACTIONATION STABILIZED BY ELECTROMAGNETIC ROTATION.

PMID- 16590635
TI  - A NEW HETEROCHROMATIN EFFECT IN DROSOPHILA MELANOGASTER.

PMID- 16590636
TI  - INHERITANCE OF ANTI-A(1) HEMAGGLUTINATING ACTIVITY IN LIMA BEANS, PHASEOLUS
      LUNATUS.

PMID- 16590637
TI  - THE HUMAN CHROMOSOMAL SATELLITES IN NORMAL PERSONS AND IN TWO PATIENTS WITH
      MARFAN'S SYNDROME.

PMID- 16590638
TI  - DIFFERENTIALS AND EXTREMAL LENGTH ON RIEMANN SURFACES.

PMID- 16590639
TI  - HOMOLOGY AND HOMOTOPY OF H-SPACES.

PMID- 16590640
TI  - ON THE USE OF ABSTRACT ALGEBRA AS A METHOD FOR OBTAINING RESULTS INVOLVING
      RATIONAL INTEGERS ONLY AND THE REVERSE OF THIS PROCEDURE.

PMID- 16590641
TI  - HOMOLOGY THEORIES AND DUALITY.

PMID- 16590642
TI  - CONTRIBUTIONS TO INFORMATION THEORY.

PMID- 16590644
TI  - ON A THEORY OF DISPERSION BY CONTINUOUS MOVEMENTS.

PMID- 16590643
TI  - SOME STATISTICAL OBSERVATIONS ON A COOPERATIVE STUDY OF HUMAN PULMONARY
      PATHOLOGY. III.

PMID- 16590645
TI  - UNITARY OPERATOR BASES.

PMID- 16590646
TI  - ESTRADIOL-17beta, ESTRONE, AND PROGESTERONE IN THE OVARIES OF DOGFISH (SQUALUS
      SUCKLEYI).

PMID- 16590647
TI  - THE BIOLOGICAL FUNCTION OF VITAMIN A ACID.

PMID- 16590648
TI  - EVIDENCE FOR A VICINAL DITHIOL IN OXIDATIVE PHOSPHORYLATION.

PMID- 16590649
TI  - THEORETICAL ANALYSIS OF TRANSPORT PROCESSES IN LIVING SYSTEMS.

PMID- 16590650
TI  - ENZYMIC MECHANISM OF INCREASED UTILIZATION OF GLUCOSE DURING VIRUS MULTIPLICATION
      IN THE CHORIOALLANTOIC MEMBRANE OF THE CHICK EMBRYO.

PMID- 16590651
TI  - THE SYNTHESIS OF 5-METHYLURIDINE 5'-PHOSPHATE IN RAT EMBRYO EXTRACTS.

PMID- 16590652
TI  - THE AMINO ACID COMPOSITION AND C-TERMINAL SEQUENCE OF A CHEMICALLY EVOKED MUTANT
      OF TMV.

PMID- 16590653
TI  - NON-VIABILITY OF STALK CELLS IN DICTYOSTELIUM.

PMID- 16590654
TI  - SIGNIFICANT STRUCTURES IN LIQUIDS, V. THERMODYNAMIC AND TRANSPORT PROPERTIES OF
      MOLTEN METALS.

PMID- 16590655
TI  - COMPARATIVE COMPLEMENTATION AND GENETIC MAPS OF THE PAN-2 LOCUS IN NEUROSPORA
      CRASSA.

PMID- 16590656
TI  - AN ENZYMATIC DIFFERENCE AMONG PYR-3 MUTANTS OF NEUROSPORA CRASSA.

PMID- 16590657
TI  - ANTAGONISM BETWEEN SUBSTRATE AND REPRESSOR IN CONTROLLING THE FORMATION OF A
      BIOSYNTHETIC ENZYME.

PMID- 16590658
TI  - THE REPLICATION OF DESOXYRIBONUCLEIC ACID IN HEPATOCYTES.

PMID- 16590659
TI  - THE EFFECT OF IRRADIATION ON THE REPLICATION OF DESOXY-RIBONUCLEIC ACID IN
      HEPATOCYTES.

PMID- 16590661
TI  - SOME MATHEMATICAL ASPECTS OF OPTIMAL PREDATION IN ECOLOGY AND BOVICULTURE.

PMID- 16590660
TI  - GENE STRUCTURE AND FUNCTION IN NEUROSPORA.

PMID- 16590662
TI  - CLASSES OF HOLOMORPHIC FUNCTIONS OF SEVERAL VARIABLES IN CIRCULAR DOMAINS.

PMID- 16590663
TI  - BETTI AND PICARD NUMBERS OF ABSTRACT ALGEBRAIC SURFACES.

PMID- 16590664
TI  - NITROGEN FIXATION BY CELL-FREE PREPARATIONS FROM MICROORGANISMS.

PMID- 16590666
TI  - THE NUCLEON-NUCLEON SPIN-ORBIT POTENTIAL.

PMID- 16590665
TI  - THE INHIBITION OF NUCLEIC ACID AND PROTEIN SYNTHESIS IN TRYPANOSOMA LEWISI BY THE
      ANTIBODY ABLASTIN.

PMID- 16590667
TI  - STUDIES IN A TEMPORAL CLASSIFICATION OF REINFORCEMENT SCHEDULES: SUMMARY AND
      PROJECTION.

PMID- 16590668
TI  - PHOSPHORYLATION COUPLED TO NITRITE OXIDATION BY PARTICLES FROM THE
      CHEMOAUTOTROPH, NITROBACTER AGILIS.

PMID- 16590669
TI  - THE FIRST STEP IN PHOTOSYNTHESIS: EVIDENCE FOR ITS ELECTRONIC NATURE.

PMID- 16590670
TI  - ANOMALOUS GROWTH OF MICROORGANISMS PRODUCED BY CHANGES IN ISOTOPES IN THEIR
      ENVIRONMENT.

PMID- 16590671
TI  - MODIFICATION OF THE STRUCTURE OF WATER IN AGAR GELS.

PMID- 16590672
TI  - STUDIES ON BEEF SPLEEN CATHEPSIN A.

PMID- 16590673
TI  - EVIDENCE FOR THE EXISTENCE OF A SINGLE-STRANDED STAGE OF T2 BACTERIOPHAGE DURING
      REPLICATION.

PMID- 16590674
TI  - ON ENZYME-SUBSTRATE RELATIONSHIPS DURING BIOCHEMICAL DIFFERENTIATION.

PMID- 16590675
TI  - A RIBONUCLEIC ACID FRACTION FROM YEAST RELATED IN COMPOSITION TO
      DESOXYRIBONUCLEIC ACID.

PMID- 16590676
TI  - PARTIAL PURIFICATION OF SOLUBLE RNA.

PMID- 16590677
TI  - A NEW REACTION OF CYCLIC ALIPHATIC ANHYDRIDES.

PMID- 16590678
TI  - URBAN PLANNING, TRANSPORTATION, AND SYSTEMS ANALYSIS.

PMID- 16590679
TI  - SYNTHETIC STERILITY IN DROSOPHILA WILLISTONI.

PMID- 16590680
TI  - THE GENETIC STRUCTURE OF THE INCOMPATIBILITY FACTORS OF SCHIZOPHYLLUM COMMUNE:
      THE A-FACTOR.

PMID- 16590682
TI  - A QUANTITATIVE FORMULATION OF SYLVESTER'S LAW OF INERTIA, II.

PMID- 16590681
TI  - CYTOLOGICAL AND PHYLOGENETIC RELATIONSHIPS IN THE REPLETA GROUP OF THE GENUS
      DROSOPHILA.

PMID- 16590683
TI  - SPECTRAL THEORY OF SMOOTHING OPERATORS.

PMID- 16590684
TI  - A NEW TYPE OF SIMPLE GROUPS OF FINITE ORDER.

PMID- 16590685
TI  - MOTION OF A GYROSCOPE ACCORDING TO EINSTEIN'S THEORY OF GRAVITATION.

PMID- 16590686
TI  - UNITARY TRANSFORMATIONS AND THE ACTION PRINCIPLE.

PMID- 16590687
TI  - CAFFEINE CONTRACTURE.

PMID- 16590688
TI  - THE EFFECT OF K, CA, I, AND TEMPERATURE ON THE CONTRACTURE OF TURTLE MUSCLE.

PMID- 16590689
TI  - THE SENSITIVITY OF NONPROPAGATING MUSCLE TO LONGITUDINAL CURRENT.

PMID- 16590690
TI  - ON THE OCCURRENCE OF CLADOCERAN REMAINS IN LAKE SEDIMENTS.

PMID- 16590691
TI  - NATIONAL ACADEMY OF SCIENCES.

PMID- 16590692
TI  - HARD SPHERE BOSE GAS: AN EXACT MOMENTUM SPACE FORMULATION.

PMID- 16590693
TI  - RADIOANGIOGRAPHIC STUDIES OF CIRCULATION IN THE MATERNAL PLACENTA OF THE RHESUS
      MONKEY: PRELIMINARY REPORT.

PMID- 16590694
TI  - EXPLORATION OF THE INTERRELATIONSHIP OF SEROTONIN WITH THE EPINEPHRINES AND
      HISTAMINE.

PMID- 16590695
TI  - A HIGH-ENERGY INTERMEDIATE OF OXIDATIVE PHOSPHORYLATION.

PMID- 16590696
TI  - DIFFERENT ENZYMIC EXPRESSIONS OF MUTANTS OF HUMAN GLUCOSE-6-PHOSPHATE
      DEHYDROGENASE.

PMID- 16590697
TI  - PRODUCTS OBTAINED BY DIGESTION OF THE NUCLEIC ACIDS OF SOME STRAINS OF TOBACCO
      MOSAIC VIRUS WITH PANCREATIC RIBONUCLEASE.

PMID- 16590698
TI  - ASSOCIATION CONSTANTS OF COMPLEX IONS: THE EVALUATION OF FREE LIGAND
      CONCENTRATION FROM MEASUREMENTS OF FREE METAL-ION CONCENTRATION.

PMID- 16590699
TI  - DESIGN AND SYNTHESIS OF A CATALYST FOR THE AEROBIC OXIDATION OF CYTOCHROME C.

PMID- 16590700
TI  - TISSUE CULTURE POPULATIONS AND THEIR RELATION TO THE TISSUE OF ORIGIN.

PMID- 16590701
TI  - GENETIC CONTROL OF PHOTOSYNTHESIS IN CHLAMYDOMONAS REINHARDI.

PMID- 16590702
TI  - THE FACTORIZATION OF CYCLIC REDUCED POWERS BY SECONDARY COHOMOLOGY OPERATIONS.

PMID- 16590703
TI  - NOTE ON POLYNOMIAL APPROXIMATION ON A JORDAN ARC.

PMID- 16590705
TI  - MOLECULAR REORIENTATION AS UNIFYING PRINCIPLE UNDERLYING CELLULAR SELECTIVITY.

PMID- 16590704
TI  - OXYGEN AND NITRIC OXIDE AS MODIFIERS OF RADIATION INJURY IN SPORES OF BACILLUS
      MEGATERIUM.

PMID- 16590706
TI  - SOIL FERTILITY, POPULATION, AND THE ANCIENT MAYA.

PMID- 16590707
TI  - FEATURES OF THE ELECTRONIC STRUCTURE OF THE IRON-PORPHYRIN COMPLEXES WITH SPECIAL
      REFERENCE TO THE OXIDO-REDUCTIVE PROPERTIES OF CYTOCHROMES.

PMID- 16590708
TI  - ENZYMATIC INCORPORATION OF RIBONUCLEOSIDE TRIPHOSPHATES INTO THE
      INTERPOLYNUCLEOTIDE LINKAGES OF RIBONUCLEIC ACID.

PMID- 16590709
TI  - FORMATION OF THE PEPTIDE CHAIN OF HEMOGLOBIN.

PMID- 16590710
TI  - SPECIFIC ANTIBODIES TO THERMALLY DENATURED DEOXYRIBONUCLEIC ACID OF PHAGE T4.

PMID- 16590711
TI  - A HYBRID HELIX CONTAINING BOTH DEOXYRIBOSE AND RIBOSE POLYNUCLEOTIDES AND ITS
      RELATION TO THE TRANSFER OF INFORMATION BETWEEN THE NUCLEIC ACIDS.

PMID- 16590712
TI  - ADENOSINE 5'-PHOSPHOSULFATE AS AN INTERMEDIATE IN THE OXIDATION OF THIOSULFATE BY
      THIOBACILLUS THIOPARUS.

PMID- 16590713
TI  - ON THE INTERACTION OF COLLOIDAL PARTICLES.

PMID- 16590714
TI  - MOUSE MACROPHAGES AS HOST CELLS FOR THE MOUSE HEPATITIS VIRUS AND THE GENETIC
      BASIS OF THEIR SUSCEPTIBILITY.

PMID- 16590715
TI  - FREQUENCY OF DELETIONS AMONG SPONTANEOUS AND INDUCED MUTATIONS IN SALMONELLA.

PMID- 16590716
TI  - STUDIES ON THE HISTOCOMPATIBILITY GENES OF THE SYRIAN HAMSTER.

PMID- 16590717
TI  - CONVEX TYPE VARIETIES.

PMID- 16590718
TI  - THE PATHS OF RAYS OF LIGHT IN GENERAL RELATIVITY.

PMID- 16590719
TI  - ON TAYLOR'S THEOREM IN SEVERAL VARIABLES.

PMID- 16590720
TI  - A SINGULARITY IN THE SCHOENFLIES EXTENSION.

PMID- 16590721
TI  - ON UNSTABLE HOMOTOPY OF SPHERES AND CLASSICAL GROUPS.

PMID- 16590722
TI  - A VIRUS IN CHICK EMBRYOS WHICH INDUCES RESISTANCE IN VITRO TO INFECTION WITH ROUS
      SARCOMA VIRUS.

PMID- 16590723
TI  - IMMUNOLOGICAL RELATIONSHIPS OF MEASLES, DISTEMPER, AND RINDERPEST VIRUSES.

PMID- 16590724
TI  - STRUCTURE AND ORIENTATION OF FREE RADICALS FORMED BY IONIZING RADIATIONS IN
      CERTAIN NATIVE PROTEINS.

PMID- 16590725
TI  - TEMPERATURE EFFECTS ON FREE RADICAL FORMATION AND ELECTRON MIGRATION IN
      IRRADIATED PROTEINS.

PMID- 16590726
TI  - DISSIPATION FUNCTIONS AND INVARIANT IMBEDDING, I.

PMID- 16590727
TI  - ON A THEORY OF DISPERSION BY CONTINUOUS MOVEMENTS, II. STATIONARY ANISOTROPIC
      PROCESSES.

PMID- 16590728
TI  - EXPERIMENTS ON THE STABILITY OF SPIRAL FLOW BETWEEN ROTATING CYLINDERS.

PMID- 16590729
TI  - STUDIES ON THE FORMATION OF AN ENZYME-SUBSTRATE COMPLEX BETWEEN MYOSIN AND
      ADENOSINETRIPHOSPHATE.

PMID- 16590730
TI  - KINETIC CONSTANTS OF THE INTERACTION BETWEEN MYOSIN AND ADENOSINETRIPHOSPHATE.

PMID- 16590731
TI  - RECONSTITUTION OF COMPLETE ORGANS FROM SINGLE-CELL SUSPENSIONS OF CHICK EMBRYOS
      IN ADVANCED STAGES OF DIFFERENTIATION.

PMID- 16590732
TI  - REAPPEARANCE OF CERTAIN STRUCTURAL FEATURES OF NATIVE COLLAGEN AFTER THERMAL
      TRANSFORMATION.

PMID- 16590733
TI  - CHEMICAL AND ENZYMATIC SYNTHESIS OF CARBAMYL PHOSPHATE.

PMID- 16590734
TI  - AMINO ACID SUPPRESSION OF RADIATION-INDUCED TUMORIZATION OF FERN PROTHALLI.

PMID- 16590735
TI  - GENETIC STUDIES ON MUTANT ENZYMES IN MAIZE: SYNTHESIS OF HYBRID ENZYMES BY
      HETEROZYGOTES.

PMID- 16590736
TI  - DIVERSE RATIOS OF MUTATIONS TO CHROMOSOME ABERRATIONS IN BARLEY TREATED WITH
      DIETHYL SULFATE AND GAMMA RAYS.

PMID- 16590737
TI  - THE THERMODYNAMICS OF SEA WATER.

PMID- 16590739
TI  - ALMOST PERIODIC SOLUTIONS OF THE INHOMOGENEOUS WAVE EQUATION.

PMID- 16590738
TI  - BEST APPROXIMATORS WITHIN A LINEAR FAMILY ON AN INTERVAL.

PMID- 16590740
TI  - CLUSTER SETS OF ARBITRARY FUNCTIONS.

PMID- 16590741
TI  - SIMPLE CURVES ON COMPACT SURFACES.

PMID- 16590742
TI  - NON-OBSTRUCTING SETS AND RELATED MAPPINGS.

PMID- 16590743
TI  - STUDIES ON EXPERIMENTAL FEVER WITH PARTICULAR REFERENCE TO THE PATHOGENETIC ROLE
      AND CHEMICAL PROPERTIES OF LEUCOCYTIC PYROGEN.

PMID- 16590744
TI  - AN UNIDENTIFIED, FILTRABLE AGENT ISOLATED FROM TRANSPLANTED HUMAN TUMORS.

PMID- 16590745
TI  - INVARIANT IMBEDDING, CONSERVATION RELATIONS, AND NONLINEAR EQUATIONS WITH TWO
      POINT BOUNDARY VALUES.

PMID- 16590746
TI  - RECENT DEVELOPMENTS IN SOLAR RADIO ASTRONOMY.

PMID- 16590747
TI  - ON THE MECHANISM OF ACTION OF THE ANTIDIURETIC HORMONE (VASOPRESSIN).

PMID- 16590748
TI  - STUDIES ON THE MECHANISM OF ACTION OF VASOPRESSIN.

PMID- 16590749
TI  - RELATION OF CHEMICAL ATTACHMENT TO PHYSIOLOGICAL ACTION OF VASOPRESSIN.

PMID- 16590750
TI  - NUCLEIC ACIDS AND METALS, II: TRANSITION METALS AS DETERMINANTS OF THE
      CONFORMATION OF RIBONUCLEIC ACIDS.

PMID- 16590751
TI  - SPIN RESONANCE STUDY OF SEROTONIN-FMN INTERACTION.

PMID- 16590752
TI  - MAMMALIAN METHYLMALONYL ISOMERASE AND VITAMIN B(12) COENZYMES.

PMID- 16590753
TI  - BIOTIN AND PROPIONYL CARBOXYLASE.

PMID- 16590754
TI  - THE FUNCTION OF ACETATE IN PHOTOSYNTHESIS BY GREEN BACTERIA.

PMID- 16590755
TI  - ON THE ELECTRON-DONATING PROPERTIES OF INDOLES.

PMID- 16590756
TI  - THE FUNCTION OF RNA IN T2-INFECTED BACTERIA.

PMID- 16590757
TI  - A COMPARISON OF ANIMAL HEMOGLOBINS BY TRYPTIC PEPTIDE PATTERN ANALYSIS.

PMID- 16590758
TI  - THE KINETICS OF DOUBLE HELIX FORMATION FROM POLYRIBOADENYLIC ACID AND
      POLYRIBOURIDYLIC ACID.

PMID- 16590759
TI  - THE CRYSTAL STRUCTURE OF TERRAMYCIN HYDROCHLORIDE.

PMID- 16590760
TI  - POPULATION STUDIES IN PREDOMINANTLY SELF-POLLINATED SPECIES, I. EVIDENCE FOR
      HETEROZYGOTE ADVANTAGE IN A CLOSED POPULATION OF BARLEY.

PMID- 16590761
TI  - GENETIC CONTROL OF SERUM TRANSFERRIN TYPE IN MICE.

PMID- 16590762
TI  - A NOTE ON LOCAL PROPERTIES OF SOLUTIONS OF ELLIPTIC DIFFERENTIAL EQUATIONS.

PMID- 16590763
TI  - DEGREE OF APPROXIMATION BY BOUNDED HARMONIC FUNCTIONS.

PMID- 16590764
TI  - CRITIQUE OF CRITICAL TABLES.

PMID- 16590765
TI  - THE SPECIAL CANONICAL GROUP.

PMID- 16590766
TI  - OPPOSITE MECHANICAL RESPONSES OF TONIC MUSCLES TO ACETYLCHOLINE STIMULATION IN
      NON-IONIC AND IONIC SOLUTIONS.

PMID- 16590767
TI  - EFFECT OF ULTRAVIOLET IRRADIATION OF BACTERIOPHAGE T2 ON ENZYME SYNTHESIS IN HOST
      CELLS.

PMID- 16590768
TI  - A POSSIBLE ROLE FOR ARGININE IN ENZYME MECHANISMS.

PMID- 16590769
TI  - THE BIOGENESIS OF THE MOLD TROPOLONES.

PMID- 16590770
TI  - ON THE ELECTRON DONATING PROPERTIES OF CARCINOGENS.

PMID- 16590771
TI  - AMINO ACID INCORPORATION INTO PROTEINS BY ESCHERICHIA COLI RIBOSOMES.

PMID- 16590772
TI  - THE COMPLETE AMINO ACID SEQUENCE OF THE PROTEIN OF TOBACCO MOSAIC VIRUS.

PMID- 16590773
TI  - EXCITATION ENERGY TRANSFER AND THE QUANTITATIVE STUDY OF THE ANTIBODY HAPTEN
      REACTION.

PMID- 16590774
TI  - STRUCTURAL ALTERATIONS IN CRYSTALLINE GLUTAMIC DEHYDROGENASE INDUCED BY STEROID
      HORMONES.

PMID- 16590775
TI  - POTASSIUM GLUCONATE AND ATP EFFECTS ON CHROMOSOME ABERRATION YIELD.

PMID- 16590776
TI  - GENETIC CONTROL OF THE alpha- AND beta-CHAINS OF HEMOGLOBIN.

PMID- 16590777
TI  - STUDIES ON THE EFFECT OF CARBON DIOXIDE ON X-RAY INDUCED CHROMOSOME ABERRATIONS
      IN TRADESCANTIA, I. DURATION OF THE PRETREATMENT EFFECT.

PMID- 16590778
TI  - BIOLOGICAL CLOCKS IN MEDICINE AND PSYCHIATRY: SHOCK-PHASE HYPOTHESIS.

PMID- 16590779
TI  - THE LOSS OF PHENOTYPIC TRAITS BY DIFFERENTIATED CELLS IN VITRO, I.
      DEDIFFERENTIATION OF CARTILAGE CELLS.

PMID- 16590780
TI  - SOME OBSERVATIONS ON THE SYNTHESIS AND FUNCTION OF THE PHOTOSYNTHETIC APPARATUS
      IN RHODOSPIRILLUM RUBRUM.

PMID- 16590781
TI  - INTERACTION OF SOLUBLE RIBONUCLEIC ACID AND MICROSOMES.

PMID- 16590782
TI  - ANALYSIS OF SEQUENCE PATTERNS IN RIBONUCLEASE, I. SEQUENCE VECTORS AND VECTOR
      MAPS.

PMID- 16590783
TI  - RECONSTITUTION OF THE DINITROPHENOL-SENSITIVE ATP-ADP EXCHANGE REACTION OF
      OXIDATIVE PHOSPHORYLATION.

PMID- 16590784
TI  - A FACTOR WHICH INCREASES THE DINITROPHENOL-SENSITIVITY OF THE ATP-ADP EXCHANGE
      REACTION OF OXIDATIVE PHOSPHORYLATION.

PMID- 16590786
TI  - SOME SINGULAR MIXED PROBLEMS.

PMID- 16590785
TI  - ON THE MUTAGENIC EFFECT OF ALKYLATING AGENTS.

PMID- 16590787
TI  - OPTIMAL GAMBLING SYSTEMS.

PMID- 16590788
TI  - FIELDS OF UNIT VECTORS IN THE FOUR-SPACE OF GENERAL RELATIVITY.

PMID- 16590789
TI  - GENERALIZED SPACES OF GENERAL RELATIVITY, II.

PMID- 16590790
TI  - SPACES WHICH ADMIT FIELDS OF NORMAL NULL VECTORS.

PMID- 16590791
TI  - A METHOD FOR DEFINING PRINCIPAL MODES OF NONLINEAR SYSTEMS UTILIZING INFINITE
      DETERMINANTS.

PMID- 16590792
TI  - INVESTIGATIONS ON FINITE GROUPS.

PMID- 16590793
TI  - CONVERGENCE IN NORM.

PMID- 16590794
TI  - SIGNIFICANCE OF CONTINUED VIRUS PRODUCTION IN TISSUE CULTURES RENDERED NEOPLASTIC
      BY POLYOMA VIRUS.

PMID- 16590795
TI  - THE SPARING EFFECT OF RMC POLIOVIRUS ON PRIMARY AMNION CELL CULTURES.

PMID- 16590796
TI  - REGULATION BY COLIPHAGE LAMBDA OF THE EXPRESSION OF THE CAPACITY TO SYNTHESIZE A
      SEQUENCE OF HOST ENZYMES.

PMID- 16590797
TI  - INVARIANT IMBEDDING AND THE REDUCTION OF TWO-POINT BOUNDARY VALUE PROBLEMS TO
      INITIAL VALUE PROBLEMS.

PMID- 16590798
TI  - TESTS OF FORM OF THE ONE-PION EXCHANGE POTENTIAL.

PMID- 16590799
TI  - A MODEL OF GROWTH AND GROWTH CONTROL IN MATHEMATICAL TERMS, II. COMPENSATORY
      ORGAN GROWTH IN THE ADULT.

PMID- 16590801
TI  - EXEMPLES DE VARIETES PROJECTIVES EN CARACTERISTIQUE p NON RELEVABLES EN
      CARACTERISTIQUE ZERO.

PMID- 16590800
TI  - LOCALLY UNKNOTTED COMBINATORIAL n-1 MANIFOLDS IN E HAVE SHELL NEIGHBORHOODS.

PMID- 16590802
TI  - A FAVORABLE STRATEGY FOR TWENTY-ONE.

PMID- 16590803
TI  - STRENGTHENING OF SPERNER'S LEMMA APPLIED TO HOMOLOGY THEORY.

PMID- 16590804
TI  - ON THE BOUND STATES OF A GIVEN POTENTIAL.

PMID- 16590805
TI  - ON THE PRESERVATION OF ANTIGENIC DETERMINANTS DURING FIXATION AND EMBEDDING FOR
      ELECTRON MICROSCOPY.

PMID- 16590806
TI  - THE ESSENTIALITY OF COBALT FOR SOYBEAN PLANTS GROWN UNDER SYMBIOTIC CONDITIONS.

PMID- 16590807
TI  - AUXIN-KINETIN INTERACTION REGULATING THE SCOPOLETIN AND SCOPOLIN LEVELS IN
      TOBACCO TISSUE CULTURES.

PMID- 16590808
TI  - NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY: ABNORMAL SPLITTING OF ETHYL GROUPS DUE
      TO MOLECULAR ASSYMETRY.

PMID- 16590809
TI  - INHIBITION BY PERIODATE OF MATING IN ESCHERICHIA COLI K-12.

PMID- 16590810
TI  - COMPARISON OF THEORETICAL WITH OBSERVED VALUES OF THE PERIODS OF FREE OSCILLATION
      OF THE EARTH.

PMID- 16590811
TI  - RINGS AND QUASICONFORMAL MAPPINGS IN SPACE.

PMID- 16590812
TI  - FORMATION OF HETEROZYGOTES BY ANNEALING A MIXTURE OF TRANSFORMING DNAS.

PMID- 16590813
TI  - THE KINETICS OF CARRIER-MEDIATED ACTIVE TRANSPORT OF AMINO ACIDS.

PMID- 16590814
TI  - A KINETIN-LIKE COMPOUND IN MAIZE.

PMID- 16590815
TI  - STABILIZATION OF NH IN HYDROCARBON MATRICES AND ITS RELATION TO COMETARY
      PHENOMENA.

PMID- 16590816
TI  - THE FUNDAMENTAL FREE MODE OF THE EARTH'S INNER.

PMID- 16590817
TI  - THE CATEGORY OF TOPOLOGICAL OBJECTS.

PMID- 16590818
TI  - DEGREE OF APPROXIMATION TO A CONTINUOUS FUNCTION ON A NON-ANALYTIC CURVE.

PMID- 16590819
TI  - SOME ASPECTS OF THE FERMAT PROBLEM (FIRST PAPER).

PMID- 16590820
TI  - THE POSSIBILITY OF TSCHEBYCHEFF QUADRATURE ON INFINITE INTERVALS.

PMID- 16590821
TI  - A RADIOBIOLOGICAL ANALOGY BETWEEN MEASLES VIRUS AND TEMPERATURE PHAGES.

PMID- 16590823
TI  - EFFECT OF SURFACE TENSION ON THE KELVIN-HELMHOLTZ INSTABILITY OF TWO ROTATING
      FLUIDS.

PMID- 16590822
TI  - INVESTIGATION OF DISEASE RESISTANCE AND THE MATHEMATICAL PROBLEM OF PATTERNS.

PMID- 16590824
TI  - ON A MANY-DIMENSIONAL BWK APPROXIMATION.

PMID- 16590825
TI  - THE EFFECTS OF REDUCED COMPETITION IN BIRDS.

PMID- 16590826
TI  - ANALYSIS OF SEQUENCE PATTERNS IN RIBONUCLEASE, II. PRIMITIVE GROUPS, THEIR
      COORDINATIONS, AND PERIODICITY.

PMID- 16590827
TI  - METHYLMALONYL ISOMERASE, II. PURIFICATION AND PROPERTIES OF THE ENZYME FROM
      PROPIONIBACTERIA.

PMID- 16590828
TI  - THE IONIC CENTRIFUGE AND FUSION NUCLEAR POWER.

PMID- 16590829
TI  - PRESSURE SHOCKS IN VISCOUS HEAT-CONDUCTING GASES.

PMID- 16590830
TI  - SOME RESULTS ON THE MODULI OF RIEMANN SURFACES.

PMID- 16590831
TI  - THE SCHOENFLIES THEOREM FOR POLYHEDRA.

PMID- 16590832
TI  - ON SUMS OF INDEPENDENT RANDOM VARIABLES WITH INFINITE MOMENTS AND "FAIR" GAMES.

PMID- 16590833
TI  - ON THE FUNDAMENTAL EQUATIONS OF INVARIANT IMBEDDING, I.

PMID- 16590834
TI  - DYNAMIC PROGRAMMING, SEQUENTIAL ESTIMATION AND SEQUENTIAL DETECTION PROCESSES.

PMID- 16590835
TI  - THE GEODESICS IN GODEL'S UNIVERSE.

PMID- 16590836
TI  - ABSENCE OF DISPERSIVE PROPERTIES OF SPACE FOR ELECTROMAGNETIC RADIATION TESTED TO
      +/- 14 x 10; COMMENTS ON A PROPOSAL OF SOFTKY AND SQUIRE.

PMID- 16590837
TI  - CRITICALITY ESTIMATES FOR SPHERES AND SLABS.

PMID- 16590838
TI  - THE ROTATIONAL SPLITTING OF THE FREE OSCILLATIONS OF THE EARTH.

PMID- 16590839
TI  - EQUATION OF RADIATIVE TRANSFER IN A PLANETARY SPHERICAL ATMOSPHERE.

PMID- 16590840
TI  - ON THE TOPOGRAPHY OF THE GENETIC FINE STRUCTURE.

PMID- 16590841
TI  - FURAZAN OXIDES, I. THE STRUCTURE OF BENZOFURAZAN OXIDE.

PMID- 16590842
TI  - A CHEMICAL SYNTHESIS OF ISOMALTOSE.

PMID- 16590844
TI  - A CHARACTERIZATION OF ABELIAN eta(alpha)-GROUPS IN TERMS OF THEIR NATURAL
      VALUATION.

PMID- 16590843
TI  - A MATHEMATICAL AID IN OPTIMIZING ENGINEERING DESIGNS, II.

PMID- 16590845
TI  - NEGATIVE ENTROPY AND PHOTOSYNTHESIS.

PMID- 16590846
TI  - REMARKS ON LORENTZ CONTRACTION.

PMID- 16590847
TI  - THE THERMOSTATIC CONTROL OF HUMAN METABOLIC HEAT PRODUCTION.

PMID- 16590848
TI  - NATIONAL ACADEMY OF SCIENCES.

PMID- 16590849
TI  - AMBIVALENT rII MUTANTS OF PHAGE T4.

PMID- 16590851
TI  - AN ALGEBRA OF ADDITIVE RELATIONS.

PMID- 16590850
TI  - TRANSPLANTATION IMMUNITY, IMMUNOLOGICAL TOLERANCE, AND CHICKEN x TURKEY
      INTERSPECIFIC HYBRIDS.

PMID- 16590852
TI  - REMARKS ON SPECTRA OF OPERATORS ON A LOCALLY CONVEX SPACE.

PMID- 16590853
TI  - ON THE WEIGHTED POLYNOMIAL APPROXIMATION IN A LOCALLY COMPACT SPACE.

PMID- 16590854
TI  - ON A NEW COMPUTATIONAL SOLUTION OF TIME-DEPENDENT TRANSPORT PROCESSES, I. ONE
      DIMENSIONAL CASE.

PMID- 16590855
TI  - QUANTUM VARIABLES AND THE ACTION PRINCIPLE.

PMID- 16590856
TI  - PHOTORECEPTORS IN THE AMPHIBIAN FRONTAL ORGAN.

PMID- 16590858
TI  - THE CLASSIFICATION OF CLUSTERS OF GALAXIES.

PMID- 16590857
TI  - OBSERVATION OF LOOP-TYPE PROMINENCES IN PROJECTION AGAINST THE DISK AT THE TIME
      OF CERTAIN SOLAR FLARES.

PMID- 16590859
TI  - THE IDENTIFICATION OF PHYSIOLOGICAL RACES OF A FUNGAL PHYTOPATHOGEN USING STRAINS
      OF THE SLIME MOLD ACRASIS ROSEA.

PMID- 16590860
TI  - EVIDENCE FOR HYDROGEN BONDING IN THIOLS FROM N.M.R. MEASUREMENTS.

PMID- 16590861
TI  - A NEW TYPE OF BORON HYDRIDE, B(10)H(16).

PMID- 16590862
TI  - A THREE-COMPONENT THEORY OF SEDIMENTATION EQUILIBRIUM IN A DENSITY GRADIENT.

PMID- 16590863
TI  - THE OCCURRENCE OF NATURAL DNA-RNA COMPLEXES IN E. COLI INFECTED WITH T2.

PMID- 16590864
TI  - CORRELATION BETWEEN BASE COMPOSITION OF DEOXYRIBONUCLEIC ACID AND AMINO ACID
      COMPOSITION OF PROTEIN.

PMID- 16590866
TI  - ON THERMODYNAMIC COUPLING OF CHEMICAL REACTIONS.

PMID- 16590865
TI  - ON THE SPECIES SPECIFICITY OF ACCEPTOR RNA AND ATTACHMENT ENZYMES.

PMID- 16590867
TI  - THEORETICAL STRUCTURE OF PLASMA EQUATIONS AND APPLICATION TO A SIMPLE PROBLEM.

PMID- 16590868
TI  - RENORMALIZATION TECHNIQUES AND MEAN SQUARE AVERAGING, I. DETERMINISTIC EQUATIONS.

PMID- 16590869
TI  - ON GROUP REPRESENTATIONS OVER A VALUATION RING.

PMID- 16590870
TI  - SOLUTION OF THE [unk]-NEUMANN PROBLEM ON STRONGLY PSEUDO-CONVEX MANIFOLDS.

PMID- 16590871
TI  - EXAMPLES FOR DIFFERENTIABLE GROUP ACTIONS ON SPHERES.

PMID- 16590872
TI  - DEFORMATION OF PSEUDOGROUP STRUCTURES.

PMID- 16590873
TI  - GRAPHICAL ANALYSIS OF MULTI-RESPONSE EXPERIMENTAL DATA USING ORDERED DISTANCES.

PMID- 16590874
TI  - MANY-ELECTRON THEORY OF ATOMS AND MOLECULES.

PMID- 16590875
TI  - RESPIRATORY ENZYME CHANGES DURING FROG EMBRYOGENESIS.

PMID- 16590876
TI  - INTRODUCTION-SURVEY OF RESEARCH FIELDS AND NEEDS.

PMID- 16590877
TI  - SOLAR ENERGY IN THE EXPLORATION OF SPACE.

PMID- 16590878
TI  - IDENTIFICATION OF 5' LINKED ADENOSINE AS END GROUP OF TMV-RNA.

PMID- 16590879
TI  - THE ENZYMATIC SYNTHESIS OF RNA: NEAREST-NEIGHBOR BASE FREQUENCIES.

PMID- 16590880
TI  - BIOCHEMICAL CONTROL OF STOMATAL OPENING IN LEAVES.

PMID- 16590881
TI  - THE PROTON IRRADIATION OF METHANE, AMMONIA, AND WATER AT 77 degrees K.

PMID- 16590882
TI  - THE STAGE OF THE GENOME-PLASMON INTERACTION IN THE RESTORATION OF FERTILITY TO
      CYTOPLASMICALLY POLLEN-STERILE MAIZE.

PMID- 16590883
TI  - ON THE SUPERSOLVABILITY OF BICYCLIC GROUPS.

PMID- 16590884
TI  - A SIMPLIFIED PROOF OF VON NEUMANN'S COORDINATIZATION THEOREM.

PMID- 16590885
TI  - WAVE BRANCHING PROCESSES AND INVARIANT IMBEDDING, I.

PMID- 16590886
TI  - SYSTEMS OF DIFFERENTIAL EQUATIONS WITHOUT LINEAR TERMS.

PMID- 16590887
TI  - ON 2-SPHERES IN 4-MANIFOLDS.

PMID- 16590888
TI  - AN ALGORITHM FOR EQUILIBRIUM POINTS IN BIMATRIX GAMES.

PMID- 16590889
TI  - ORBIT SPACES OF FINITE ABELIAN TRANSFORMATION GROUPS.

PMID- 16590891
TI  - TWO CHANGES IN THE USUAL EQUATIONS OF A PLASMA REQUIRED FOR MAGNETODYNAMIC WORK.

PMID- 16590890
TI  - ON THE DIFFERENT MOLECULAR FORMS OF ANTIBODY SYNTHESIZED BY RABBITS DURING THE
      EARLY RESPONSE TO A SINGLE INJECTION OF PROTEIN AND CELLULAR ANTIGENS.

PMID- 16590892
TI  - WOODRING CONFERENCE ON MAJOR BIOLOGIC INNOVATIONS AND THE GEOLOGIC RECORD.

PMID- 16590893
TI  - EVOLUTION OF GASEOUS NEBULAE.

PMID- 16590894
TI  - AN EVALUATION OF STUDIES ON ULTRASTRUCTURE OF SIEVE PLATES.

PMID- 16590895
TI  - IN SITU DETECTION AND ESTIMATION OF CHLOROPHYLL AND OTHER PIGMENTS IN THE OCEAN.

PMID- 16590896
TI  - POLARIZATION OF THE ULTRAVIOLET ABSORPTION BANDS IN alpha-HELICAL POLYPEPTIDES.

PMID- 16590897
TI  - EXTENSIONS OF THE VALENCE THEORY OF BORON COMPOUNDS.

PMID- 16590898
TI  - INTERACTIONS OF BORANES AND THEIR IONS WITH PARAMAGNETIC S-STATE IONS.

PMID- 16590899
TI  - THE OCCURRENCE OF GAS HYDRATES IN THE SOLAR SYSTEM.

PMID- 16590900
TI  - MODES IN SEQUENCES OF LENSES.

PMID- 16590901
TI  - THE PATHS OF RAYS OF LIGHT IN GENERAL RELATIVITY OF THE NONSYMMETRIC FIELD V(4).

PMID- 16590902
TI  - A NEW TECHNIQUE FOR THE CONSTRUCTION OF SOLUTIONS OF NONLINEAR DIFFERENTIAL
      EQUATIONS.

PMID- 16590903
TI  - SOME ASPECTS OF THE FERMAT PROBLEM (THIRD PAPER).

PMID- 16590904
TI  - CONFORMAL MAPS OF SMALL DISKS.

PMID- 16590905
TI  - COMPRESSIBILITY AND UNIFORM CONVERGENCE.

PMID- 16590906
TI  - ACHIEVEMENT OF SEDIMENTATION EQUILIBRIUM.

PMID- 16590907
TI  - RELATIVISTIC UNIVERSES WITH SHEAR.

PMID- 16590908
TI  - AN EVALUATION OF STUDIES ON ULTRASTRUCTURE OF TONOPLAST IN SIEVE ELEMENTS.

PMID- 16590909
TI  - THE INDUCTION OF BALANCED HETEROTHALLISM IN SORDARIA FIMICOLA.

PMID- 16590911
TI  - SPACES IN WHICH THE GEODESICS ARE MINIMAL CURVES.

PMID- 16590910
TI  - SUBORDINATION OF NON-GAUSSIAN STOCHASTIC PROCESSES.

PMID- 16590912
TI  - SOME FUNCTION CLASSES CONNECTED WITH PARTIALLY HYPOELLIPTIC DIFFERENTIAL
      OPERATORS.

PMID- 16590913
TI  - THE CONFORMAL TRANSFORMATION GROUP OF A COMPACT RIEMANNIAN MANIFOLD.

PMID- 16590914
TI  - DEGREE OF POLYNOMIAL APPROXIMATION TO AN ANALYTIC FUNCTION AS MEASURED BY A
      SURFACE INTEGRAL.

PMID- 16590915
TI  - MASS SPECTROMETRY IN STRUCTURAL AND STEREOCHEMICAL PROBLEMS, IV. VINDOLININE.

PMID- 16590916
TI  - MECHANISMS UNDERLYING THE EQUILIBRIUM REACTIONS BETWEEN IONS AND ION-PAIRS IN
      SOLUTIONS OF ELECTROLYTES, I. SOLUTIONS IN p-XYLENE AT 52 degrees C AND BENZENE
      AT 25 degrees C.

PMID- 16590917
TI  - INDEPENDENCE OF CONTAINMENT TIME OF A PLASMA UPON THE STRENGTH OF A MAGNETIC
      FIELD.

PMID- 16590918
TI  - NEW TECHNIQUES IN ANALYSIS OF COMPLEX NATURAL HYBRIDIZATION.

PMID- 16590919
TI  - EFFECTS OF FLUORODEOXYURIDINE ON DNA REPLICATION, CHROMOSOME BREAKAGE, AND
      REUNION.

PMID- 16590920
TI  - REMARKS ON A HILBERT SPACE OF ANALYTIC FUNCTIONS.

PMID- 16590921
TI  - ABSTRACT ERGODIC THEOREMS.

PMID- 16590922
TI  - A THEOREM ON CURVATURE TENSOR FIELDS.

PMID- 16590923
TI  - AN APPARENT LUNAR PERIODICITY IN THE SEXUAL CYCLE OF CERTAIN PROSIMIANS.

PMID- 16590925
TI  - OBSERVATIONS OF RUBY-LASER BEAM-INTENSITY PATTERNS WITH DYE-SENSITIZED
      PHOTOPOLYMERS.

PMID- 16590924
TI  - PROPIONIC ACID METABOLISM: MECHANISM OF THE METHYLMALONYL ISOMERASE REACTION AND
      THE REDUCTION OF ACRYLYL COENZYME A TO PROPIONYL COENZYME A IN PROPIONIBACTERIA.

PMID- 16590926
TI  - THUNDERSTORMS AS RELATED TO ORGANIC MATTER IN THE ATMOSPHERE.

PMID- 16590927
TI  - EVAPORATION RESISTANCE AS A SENSITIVE MEASURE OF THE PURITY AND MOLECULAR
      STRUCTURE OF MONOLAYERS.

PMID- 16590928
TI  - ON THE DERIVATION OF HISTONE SPECIFICITY.

PMID- 16590929
TI  - CONVOLUTION OPERATORS ON BANACH SPACE VALUED FUNCTIONS.

PMID- 16590930
TI  - ENTSCHEIDUNGSPROBLEM REDUCED TO THE AEA CASE.

PMID- 16590931
TI  - RADIATION DAMPING OF SPINNING PARTICLES.

PMID- 16590932
TI  - BIMODAL OCCURRENCE OF BREEDING IN AN EQUATORIAL SPARROW.

PMID- 16590933
TI  - METABOLISM OF MYO-INOSITOL IN PLANTS: CONVERSION TO PECTIN, HEMICELLULOSE, D
      XYLOSE, AND SUGAR ACIDS.

PMID- 16590934
TI  - A THEORY ON THE MECHANISM OF MESSENGER-RNA SYNTHESIS.

PMID- 16590935
TI  - AN RNA-PROTEIN CODE BASED ON REPLACEMENT DATA.

PMID- 16590936
TI  - EFFECTS OF REDUCED OXYGEN TENSION ON VASCULAR PLANTS, IV. WINTER RYE GERMINATION
      UNDER NEAR-MARTIAN CONDITIONS AND IN OTHER NONTERRESTRIAL ENVIRONMENTS.

PMID- 16590937
TI  - REACTIONS OF B(10)H(10) ION.

PMID- 16590938
TI  - THE STEREOCHEMISTRY OF FUMAGILLIN.

PMID- 16590939
TI  - ON THE CAUSE OF THE TEMPERATURE-SALINITY CURVE IN THE OCEAN.

PMID- 16590940
TI  - ON THE SMALLNESS OF SINKING REGIONS IN THE OCEAN.

PMID- 16590941
TI  - THE PATHS OF RAYS OF LIGHT IN GENERALIZED GENERAL RELATIVITY OF THE NONSYMMETRIC
      FIELD V(4).

PMID- 16590942
TI  - THE MARTIN BOUNDARY.

PMID- 16590943
TI  - ON CERTAIN HOMOGENEOUS COMPLEX MANIFOLDS.

PMID- 16590944
TI  - DUALITY, HAAR PROGRAMS, AND FINITE SEQUENCE SPACES.

PMID- 16590945
TI  - GLOBAL CROSS SECTIONS OF COMPACT DYNAMICAL SYSTEMS.

PMID- 16590946
TI  - PROBABILITIES ON LIE GROUPS.

PMID- 16590947
TI  - NOTE ON SECOND-ORDER W. K. B. PHASE SHIFTS.

PMID- 16590948
TI  - INDETERMINISM IN INTERSPECIFIC COMPETITION.

PMID- 16590949
TI  - FINE STRUCTURE OF PHOTORECEPTORS IN THE HYDROMEDUSAN, POLYORCHIS PENICILLATUS.

PMID- 16590950
TI  - A FATTY ACID SYNTHETASE FROM E. COLI.

PMID- 16590951
TI  - THE SPECIFICITY OF INCORPORATION OF GLUTAMIC ACID AND GLUTAMINE INTO PROTEIN.

PMID- 16590953
TI  - OPTICAL ROTATORY DISPERSION AND THE TWIST CONFORMATION OF CYCLOHEXANONES.

PMID- 16590952
TI  - EPR IN CHROMATOPHORES FROM RHODOSPIRILLUM RUBRUM AND IN QUANTASOMES FROM SPINACH
      CHLOROPLASTS.

PMID- 16590955
TI  - GROWTH, ORIENTATION, AND X-RAY DIFFRACTION OF SINGLE CRYSTALS NEAR LIQUID HELIUM
      TEMPERATURES.

PMID- 16590954
TI  - SIMPLIFIED ROTATING CYLINDER VISCOMETER FOR DNA.

PMID- 16590956
TI  - SOME CALCULATIONS OF THE CURRENTS IN THE IONIC CENTRIFUGE.

PMID- 16590957
TI  - ORIGIN OF INDOCHINITE TEKTITES.

PMID- 16590958
TI  - ROTATION OF THE CRYSTAL LATTICE IN KINK BANDS, DEFORMATION BANDS, AND TWIN
      LAMELLAE OF STRAINED CRYSTALS.

PMID- 16590959
TI  - ON THE MARTIN BOUNDARY FOR MARKOV CHAINS.

PMID- 16590960
TI  - A SOLVABILITY CRITERION FOR FINITE GROUPS AND SOME CONSEQUENCES.

PMID- 16590961
TI  - ON INCREASING MARKOV PROCESSES.

PMID- 16590962
TI  - RAPIDLY RUNNING TRANSITIONS AT HIGH PRESSURE.

PMID- 16590963
TI  - MAGNETOHYDRODYNAMIC WAVES IN A CONSTANT DIPOLE MAGNETIC FIELD.

PMID- 16590965
TI  - EFFECT OF CHEMICAL CONTROL OF STOMATA ON TRANSPIRATION AND PHOTOSYNTHESIS.

PMID- 16590964
TI  - SURFACE RECONSTRUCTION CAUSED BY ADSORPTION.

PMID- 16590966
TI  - NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY: ABNORMAL SPLITTING OF ETHYL GROUPS DUE
      TO MOLECULAR ASYMMETRY, III.

PMID- 16590967
TI  - ON GAUSSIAN SUMS.

PMID- 16590968
TI  - ON A CLASS OF PERTURBATIONS IN QUANTUM FIELD THEORY.

PMID- 16590969
TI  - ON A HILBERT SPACE WITH NONASSOCIATIVE SCALARS.

PMID- 16590970
TI  - THE MAXIMUM CONNECTIVITY OF A GRAPH.

PMID- 16590971
TI  - LOCALLY PERIPHERALLY EUCLIDEAN SPACES ARE LOCALLY EUCLIDEAN, II.

PMID- 16590972
TI  - WEAK TOPOLOGIES FOR STOCHASTIC PROCESSES.

PMID- 16590973
TI  - EXTREMA FOR GAP POWER SERIES OF POSITIVE REAL PART.

PMID- 16590974
TI  - A COORDINATIZATION THEOREM FOR JORDAN ALGEBRAS.

PMID- 16590975
TI  - NATIONAL ACADEMY OF SCIENCES.

PMID- 16590976
TI  - EFFECT OF CHEMICAL CONTROL OF STOMATA ON TRANSPIRATION OF INTACT PLANTS.

PMID- 16590977
TI  - HYDROGEN CYANIDE DIMER AND CHEMICAL EVOLUTION.

PMID- 16590978
TI  - THE CURRENT INDUCED BY A MAGNETIC FIELD IN A PHYSICALLY BOUNDED PLASMA.

PMID- 16590979
TI  - PRELIMINARY GENETIC MAP OF SEVENTEEN GALACTOSE MUTATIONS IN E. COLI K-12.

PMID- 16590980
TI  - POPULATION STUDIES IN PREDOMINANTLY SELF-POLLINATED SPECIES, III. A MATRIX MODEL
      FOR MIXED SELFING AND RANDOM OUTCROSSING.

PMID- 16590981
TI  - ON A NEW APPROACH TO THE COMPUTATIONAL SOLUTION OF PARTIAL DIFFERENTIAL
      EQUATIONS.

PMID- 16590982
TI  - ORBIT DETERMINATION AS A MULTI-POINT BOUNDARY-VALUE PROBLEM AND
      QUASILINEARIZATION.

PMID- 16590983
TI  - A FLOQUET THEORY FOR FUNCTIONAL DIFFERENTIAL EQUATION.

PMID- 16590984
TI  - THE CAUCHY INEQUALITY IN TOPOLOGICAL ANALYSIS.

PMID- 16590985
TI  - THE LIGHT RESPONSE AND THE RHYTHMIC POTENTIALS OF HYDRA.

PMID- 16590986
TI  - CONSTITUENTS OF THE THYMUS GLAND AND THEIR RELATION TO GROWTH, FERTILITY, MUSCLE,
      AND CANCER.

PMID- 16590987
TI  - MICROENVIRONMENTS FOR LIFE ON MARS.

PMID- 16590988
TI  - HIGH PRESSURE CHEMISTRY, I: ULTRA RAPID RATES AT VERY HIGH PRESSURES.

PMID- 16590989
TI  - THE PARAMAGNETIC RESONANCE OF WURSTER'S BLUE PERCHLORATE.

PMID- 16590990
TI  - MOLECULAR STRUCTURE OF B(18)H(22).

PMID- 16590991
TI  - DIFFERENCES IN FREE AMINO ACID CONTENT OF SEEDLINGS OF AWNED AND HOODED BARLEY,
      AND THEIR ALTERATION BY CHLORAMPHENICOL TREATMENT.

PMID- 16590992
TI  - A COMPUTATIONAL PROCEDURE FOR OPTIMAL SYSTEM DESIGN AND UTILIZATION.

PMID- 16590993
TI  - GENERALIZED RIEMANNIAN GEOMETRY.

PMID- 16590994
TI  - THE SOLUTION OF SETS OF EQUATIONS IN GROUPS.

PMID- 16590995
TI  - POLYNOMIALS OF BEST APPROXIMATION ON AN INTERVAL, II.

PMID- 16590996
TI  - RELATIVISTIC QUANTUM THEORY OF PARTICLES WITH VARIABLE MASS, I.

PMID- 16590997
TI  - ON THE GEODESIC HYPOTHESIS IN THE THEORY OF GRAVITATION.

PMID- 16590998
TI  - ON THOMAS' RESULT CONCERNING THE GEODESIC HYPOTHESIS.

PMID- 16590999
TI  - INCORPORATION OF GLUTAMATE INTO RIBONUCLEIC ACID.

PMID- 16591000
TI  - ACTION OF AMYLO-1,6-GLUCOSIDASE ON LOW MOLECULAR WEIGHT SUBSTRATES AND THE ASSAY
      OF THIS ENZYME IN GLYCOGEN STORAGE DISEASE.

PMID- 16591001
TI  - LINEAR BIOSYNTHESIS OF TOBACCO MOSAIC VIRUS: EVIDENCE THAT SHORT VIRUS RODS ARE
      NATURAL PRODUCTS OF TMV BIOSYNTHESIS.

PMID- 16591002
TI  - THE APPLICATION OF PROTON SPIN-SPIN DECOUPLING TO ORGANIC STRUCTURAL PROBLEMS:
      INFORMATION ON THE STRUCTURE OF ACTINOSPECTACIN.

PMID- 16591003
TI  - "SELFERS"-ATTRIBUTED TO UNEQUAL CROSSOVERS IN SALMONELLA.

PMID- 16591004
TI  - SELECTION FOR GEOTAXIS IN MONOMORPHIC AND POLYMORPHIC POPULATIONS OF DROSOPHILA
      PSEUDOOBSCURA.

PMID- 16591006
TI  - DYNAMIC PROGRAMMING APPLIED TO CONTROL PROCESSES GOVERNED BY GENERAL FUNCTIONAL
      EQUATIONS.

PMID- 16591005
TI  - THE AGE OF SALT MARSH PEAT AND ITS RELATION TO RECENT CHANGES IN SEA LEVEL AT
      BARNSTABLE, MASSACHUSETTS.

PMID- 16591007
TI  - RELATIVISTIC QUANTUM THEORY OF PARTICLES WITH VARIABLE MASS, II.

PMID- 16591008
TI  - AN APPROXIMATE CELL MODEL FOR LIQUID HYDROGEN, I.

PMID- 16591009
TI  - ON THE MECHANISM OF TISSUE RECONSTRUCTION BY DISSOCIATED CELLS, III. FREE ENERGY
      RELATIONS AND THE REORGANIZATION OF FUSED, HETERONOMIC TISSUE FRAGMENTS.

PMID- 16591010
TI  - IN VIVO AND IN VITRO STUDIES OF HISTOCOMPATIBILI ANTIGENS ISOLATED FROM A
      CULTURED MOUSE CELL LINE.

PMID- 16591012
TI  - ELECTRON SPIN RESONANCE OF X-IRRADIATED ORGANIC INCLUSION COMPOUNDS.

PMID- 16591011
TI  - ROLE OF FERREDOXIN IN PYRIDINE NUCLEOTIDE REDUCTION.

PMID- 16591013
TI  - SOME GENERALIZED THEOREMS OF NATURAL SELECTION.

PMID- 16591014
TI  - THE CONWAY GRANITE OF NEW HAMPSHIRE AS A MAJOR LOW-GRADE THORIUM RESOURCE.

PMID- 16591015
TI  - THE CHRONOLOGY OF CALEDONIAN FOLDING IN THE BRITISH ISLES.

PMID- 16591016
TI  - A NEW FORMALISM IN PERTURBATION THEORY USING CONTINUED FRACTIONS.

PMID- 16591017
TI  - ON THE CHARACTERISTIC OF POSITIVELY-PINCHED RIEMANNIAN MANIFOLDS.

PMID- 16591018
TI  - AN EXAMPLE FOR SO(3).

PMID- 16591019
TI  - A MEASURE DISTORTION MAPPING.

PMID- 16591021
TI  - STELLAR DYNAMICS OF SPHERICAL GALAXIES.

PMID- 16591020
TI  - RNA-INDUCED BIOSYNTHESIS OF SPECIFIC ENZYMES.

PMID- 16591022
TI  - TWO PHOTOREACTIONS IN PHOTOSYNTHESIS: EVIDENCE FROM THE DELAYED LIGHT EMISSION OF
      CHLORELLA.

PMID- 16591023
TI  - THE DISTRIBUTION OF POTENTIAL ACROSS THE LOW-INDEX CRYSTAL PLANES OF GERMANIUM
      CONTACTING AN AQUEOUS.

PMID- 16591024
TI  - A CRITERION FOR THE EXISTENCE OF INERTIAL BOUNDARY LAYERS IN OCEANIC CIRCULATION.

PMID- 16591025
TI  - A NEW APPROACH TO ALMOST PERIODICITY.

PMID- 16591026
TI  - AN APPRAISAL OF THE CANCER DEATH RECORD.

PMID- 16591027
TI  - SOME FURTHER REMARKS ON THE GEODESIC HYPOTHESIS IN THE THEORY OF GRAVITATION.

PMID- 16591028
TI  - INSULIN-GROSS MOLECULAR STRUCTURE: TRIAL-AND-ERROR STUDIES USING TRANSFORM AND
      PATTERSON FUNCTION TECHNIQUES.

PMID- 16591029
TI  - CONTROL OF GLUCOSE OXIDATION IN ANTERIOR PITUITARY BY HORMONALLY SENSITIVE
      PYRIDINE NUCLEOTIDE TRANSHYDROGENASE.

PMID- 16591030
TI  - PROTEIN SYNTHESIS IN ERYTHROID CELLS, I. RETICULOCYTE RIBOSOMES ACTIVE IN
      STIMULATING AMINO ACID INCORPORATION.

PMID- 16591031
TI  - THE EFFECT OF POLYAMINES AND OF POLY U SIZE ON PHENYLALANINE INCORPORATION.

PMID- 16591034
TI  - CRYSTAL STRUCTURE OF POTASSIUM OZONIDE.

PMID- 16591032
TI  - THE CELLULAR SITES OF SYNTHESIS OF RIBOSOMAL AND 4S RNA.

PMID- 16591035
TI  - GENERALIZED RIEMANNIAN GEOMETRY, II.

PMID- 16591036
TI  - RELATIVE HOMOLOGICAL ALGEBRA MADE ABSOLUTE.

PMID- 16591037
TI  - THE SAMPLING DISTRIBUTION OF PRIMES.

PMID- 16591038
TI  - ON A PLANE ISING LATTICE WITH FIRST AND SECOND INTERACTIONS.

PMID- 16591039
TI  - NOTE ON THE SQUARE-INTEGRABILITY OF THE KERNEL OF THE LINEARIZED BOLTZMANN
      INTEGRAL EQUATION FOR RIGID SPHERE MOLECULES.

PMID- 16591040
TI  - THE DETERMINATION OF THE ELECTROPHORETIC CONTRIBUTION TO CONDUCTANCE FROM THE
      CONCENTRATION DEPENDENCE OF TRANSFERENCE NUMBERS.

PMID- 16591041
TI  - EFFECTS OF MECHANICAL SHEAR ON GENETIC ACTIVITY OF BACILLUS SUBTILIS DNA.

PMID- 16591042
TI  - INSULIN-A PROBABLE GROSS MOLECULAR STRUCTURE.

PMID- 16591043
TI  - MECHANISMS UNDERLYING THE EQUILIBRIUM REACTIONS BETWEEN IONS AND ION-PAIRS IN
      SOLUTIONS OF ELECTROLYTES, II. THE EFFECT OF TEMPERATURE.

PMID- 16591044
TI  - USE OF AN ULTRAMICROTOME FOR THE PREPARATION OF THIN SECTIONS OF SINGLE CRYSTALS
      FOR ABSORPTION SPECTROSCOPY.

PMID- 16591045
TI  - APPARENT CYTOPLASMIC STERILITY IN DROSOPHILA PAULISTORUM.

PMID- 16591046
TI  - A DISCUSSION AND PROPOSALS CONCERNING FOSSIL DINOFLAGELLATES, HYSTRICHOSPHERES,
      AND ACRITARCHS, I.

PMID- 16591047
TI  - SPIN (1/2) WAVE EQUATION IN DE-SITTER SPACE.

PMID- 16591048
TI  - LYAPUNOV FUNCTIONS FOR THE PROBLEM OF LUR'E IN AUTOMATIC CONTROL.

PMID- 16591049
TI  - REGULARITY AT THE BOUNDARY OF THE delta-NEUMANN PROBLEM.

PMID- 16591050
TI  - ON THEORIES CATEGORICAL IN UNCOUNTABLE POWERS.

PMID- 16591051
TI  - BOUNDS OF ANALYTIC FUNCTIONS OF TWO COMPLEX VARIABLES IN DOMAINS WITH THE BERGMAN
      SILOV BOUNDARY.

PMID- 16591052
TI  - IDENTIFICATION OF THE IMMUNE SYSTEM RESPONSIBLE FOR THE SPECIFICITY OF ACTIVELY
      ACQUIRED TOLERANCE IN MICE.

PMID- 16591053
TI  - ILLEGITIMACY AND SPECIFIC FACTOR TRANSFER IN SCHIZOPHYLLUM COMMUNE.

PMID- 16591054
TI  - THE DEPENDENCE OF VIABILITY EFFECTS CAUSED BY IRRADIATION ON THE TYPE OF MATING.

PMID- 16591055
TI  - A DISCUSSION AND PROPOSALS CONCERNING FOSSIL DINOFLAGELLATES, HYSTRICHOSPHERES,
      AND ACRITARCHS, II.

PMID- 16591056
TI  - RESTRICTED INFRAPOLYNOMIALS AND TRIGONOMETRIC INFRAPOLYNOMIALS.

PMID- 16591057
TI  - BIOSYNTHESIS OF VALINE AND ISOLEUCINE, VI. ENZYME REPRESSION IN SALMONELLA.

PMID- 16591058
TI  - AN APPROACH TO THE EVOLUTION OF METABOLISM.

PMID- 16591060
TI  - DIRECT AND OPTICAL ASSAY OF LEAF MASS OF THE LOWER MONTANE RAIN FOREST OF PUERTO
      RICO.

PMID- 16591059
TI  - CHLORAMPHENICOL-PROMOTED REPRESSION OF beta-GALACTOSIDASE SYNTHESIS IN
      ESCHERICHIA COLI.

PMID- 16591061
TI  - INCORPORATION OF 5-IODODEOXYURIDINE INTO DNA OF PLANT CELLS.

PMID- 16591062
TI  - DUALITY FOR COMPACT GROUPS.

PMID- 16591063
TI  - ON SPRAYS AND HIGHER ORDER CONNECTIONS.

PMID- 16591064
TI  - ALMOST AUTOMORPHIC FUNCTIONS.

PMID- 16591065
TI  - AN APPROXIMATE CELL MODEL FOR LIQUID HYDROGEN, II.

PMID- 16591066
TI  - MOLECULAR GENETICS OF AVIAN PROTEINS, II. CONTROL GENES AND STRUCTURAL GENES FOR
      EMBRYONIC AND ADULT HEMOGLOBINS.

PMID- 16591067
TI  - DYNAMIC ROLE OF TRIPLET STATES IN PHOTOSYNTHESIS.

PMID- 16591068
TI  - THE SPECIES VARIATION OF RNA METHYLASE.

PMID- 16591069
TI  - HUMAN SEX CHROMOSOME ABNORMALITIES IN RELATION TO DNA REPLICATION AND
      HETEROCHROMATINIZATION.

PMID- 16591070
TI  - INCORPORATION OF PARENTAL DNA INTO GENETIC RECOMBINANTS OF E. COLI.

PMID- 16591072
TI  - ROTATION TENSORS AND IRROTATIONAL MOTIONS IN EINSTEIN-RIEMANN SPACES.

PMID- 16591071
TI  - GENETICS OF A GAMMA GLOBULIN ISOANTIGEN (ALLOTYPE) IN THE MOUSE.

PMID- 16591073
TI  - SOME ASPECTS OF THE FERMAT PROBLEM (FOURTH PAPER).

PMID- 16591074
TI  - THE VIRAL THEOREM IN GENERAL RELATIVITY IN THE POST-NEWTONIAN APPROXIMATION.

PMID- 16591075
TI  - IMMUNOASSAY OF BOVINE AND HUMAN PARATHYROID HORMONE.

PMID- 16591076
TI  - GLIAL RNA CHANGES DURING A LEARNING EXPERIMENT IN RATS.

PMID- 16591077
TI  - MATING BEHAVIOR IN MALE RATS AFTER REMOVAL OF THE SEMINAL VESICLES.

PMID- 16591078
TI  - THE DEVELOPMENT OF SOMATIC MUTATIONS IN MICE WITH AGE.

PMID- 16591079
TI  - REPRESSION OF THE VALINE-ISOLEUCINE PATHWAY IN SALMONELLA.

PMID- 16591080
TI  - ON THE LIGHT-INDUCED BLEACHING OF PHOTOSYNTHETIC PYRIDINE NUCLEOTIDE REDUCTASE IN
      THE PRESENCE OF CHLOROPLASTS.

PMID- 16591081
TI  - PIG HEART GLUTAMIC ASPARTIC TRANSAMINASE MECHANISM OF TRANSAMINATION.

PMID- 16591082
TI  - THE IDENTIFICATION OF A SULFATED MUCOPOLYSACCHARIDE IN CHICK EMBRYOS, STAGES 11
      23.

PMID- 16591083
TI  - MOLECULAR FACETS OF MITOTIC REGULATION, I. SYNTHESIS OF THYMIDINE KINASE.

PMID- 16591084
TI  - POLYRIBOSOMES IN NORMAL AND POLIOVIRUS-INFECTED HELA CELLS AND THEIR RELATIONSHIP
      TO MESSENGER-RNA.

PMID- 16591085
TI  - PYRIMIDINE-SPECIFIC ANTIBODIES WHICH REACT WITH DEOXYRIBONUCLEIC ACID (DNA).

PMID- 16591086
TI  - THE FUNCTION OF sRNA AS AMINO ACID ADAPTOR IN THE SYNTHESIS OF HEMOGLOBIN.

PMID- 16591087
TI  - PHOTOELECTRIC SPECTROPHOTOMETRY OF PLANETARY NEBULAE.

PMID- 16591088
TI  - QUANTIZATION AND METASTABILITY OF SUPERCURRENTS.

PMID- 16591089
TI  - RESOLUTION OF DUAL MECHANISMS OF POTASSIUM ABSORPTION BY BARLEY ROOTS.

PMID- 16591090
TI  - SYNTHESIS OF TRANSFER RNA BY ISOLATED NUCLEI.

PMID- 16591091
TI  - THE SYNTHESIS OF MESSENGER RNA WITHOUT PROTEIN SYNTHESIS IN NORMAL AND PHAGE
      INFECTED THYMINELESS STRAINS OF ESCHERICHIA COLI.

PMID- 16591092
TI  - THE SECONDARY STRUCTURE OF REOVIRUS RNA.

PMID- 16591093
TI  - SEPARATION OF LIGHT AND DARK STAGES IN PHOTOPHOSPHORYLATION.

PMID- 16591094
TI  - THE AMINO ACID SEQUENCE OF A TETRADECAPEPTIDE CONTAINING THE REACTIVE SERINE IN
      E. COLI ALKALINE PHOSPHATASE.

PMID- 16591095
TI  - SEPARATION OF THE RNA MESSAGE TRANSCRIBED IN RESPONSE TO A SPECIFIC INDUCER.

PMID- 16591096
TI  - FORMATION OF ADENINE BY ELECTRON IRRADIATION OF METHANE, AMMONIA, AND WATER.

PMID- 16591097
TI  - DECOMPOSITION AND EQUIVALENCE OF LOCAL VECTOR FIELDS.

PMID- 16591098
TI  - STUDIES ON CELL AGGREGATION: DEMONSTRATION OF MATERIALS WITH SELECTIVE CELL
      BINDING ACTIVITY.

PMID- 16591099
TI  - COHESION OF DNA MOLECULES ISOLATED FROM PHAGE LAMBDA.

PMID- 16591100
TI  - CHAIRMAN'S INTRODUCTION.

PMID- 16591101
TI  - TOPOTACTIC REACTIONS IN ORGANIC CRYSTALS.

PMID- 16591103
TI  - SOME REMARKS ON AUTOMORPHISMS, ANALYTIC BUNDLES, AND EMBEDDINGS OF COMPLEX
      ALGEBRAIC VARIETIES.

PMID- 16591102
TI  - ON CURVATURE AND EULER-POINCARE CHARACTERISTIC.

PMID- 16591104
TI  - A NONLOCAL FUNCTION ALGEBRA.

PMID- 16591105
TI  - ON MODULAR CORRESPONDENCES FOR SP(N, Z) AND THEIR CONGRUENCE RELATIONS.

PMID- 16591106
TI  - A UNIFYING PRINCIPAL IN QUANTIFICATION THEORY.

PMID- 16591107
TI  - CHIMPANZEE BEHAVIOR: REMOVAL OF FOREIGN BODY FROM CAMPANION'S EYE.

PMID- 16591109
TI  - INFORMATION CONTENTS OF DISTRIBUTIONS.

PMID- 16591108
TI  - BIOPHYSICAL CHARACTERISTICS OF THE RNA-CONTAINING BACTERIAL VIRUS R17.

PMID- 16591110
TI  - THE EINSTEIN GENERALIZED RIEMANNIAN GEOMETRY.

PMID- 16591111
TI  - EVIDENCE FOR A REQUIREMENT FOR PROTEIN SYNTHESIS FOR AUXIN-INDUCED CELL
      ENLARGEMENT.

PMID- 16591112
TI  - HYPERSONIC CHEMOSYNTHESIS AND POSSIBLE FORMATION OF ORGANIC COMPOUNDS FROM IMPACT
      OF METEORITES ON WATER.

PMID- 16591113
TI  - MECHANISM FOR SELF-DIFFUSION IN ICE.

PMID- 16591114
TI  - ON THE STRUCTURE OF COMPACT COMPLEX ANALYTIC SURFACES.

PMID- 16591116
TI  - A GENERALIZATION OF BOUNDED HAAR MEASURE.

PMID- 16591115
TI  - INVARIANT IMBEDDING AND RAREFIED GAS DYNAMICS.

PMID- 16591117
TI  - COMPUTER-COMPILED OCEANOGRAPHIC ATLAS: AN EXPERIMENT IN MAN-MACHINE INTERACTION.

PMID- 16591118
TI  - THE INTEGRATION OF THE FIRST-ORDER PERTURBED WAVE EQUATION FOR EXCITED STATES OF
      ONE-DIMENSIONAL SYSTEMS.

PMID- 16591119
TI  - NOTE ON THE CONVERGENCE OF APPROXIMATING RATIONAL FUNCTIONS OF PRESCRIBED TYPE.

PMID- 16591121
TI  - SOME EFFECTS OF SOLVATION UPON OPTICALLY ACTIVE MOLECULES.

PMID- 16591120
TI  - VARIATIONAL BOUNDARY VALUE PROBLEMS FOR QUASI-LINEAR ELLIPTIC EQUATIONS, III.

PMID- 16591122
TI  - NOTE ON THE LINEARIZED BOLTZMANN INTEGRAL EQUATION FOR RIGID SPHERE MOLECULES.

PMID- 16591123
TI  - THE EFFECT OF MITOTIC CYCLE DURATION ON CHROMOSOME BREAKAGE IN MERISTEMATIC CELLS
      OF PISUM SATIVUM.

PMID- 16591124
TI  - TREE LINES AND GERM PLASM-A STUDY IN EVOLUTIONARY LIMITATIONS.

PMID- 16591125
TI  - FUNCTORIAL SEMANTICS OF ALGEBRAIC THEORIES.

PMID- 16591127
TI  - A NEW TYPE OF NON ASSOCIATIVE ALGEBRAS.

PMID- 16591126
TI  - A STABILITY THEOREM FOR FUNCTIONAL-DIFFERENTIAL EQUATIONS.

PMID- 16591128
TI  - THE EULER CLASS AS AN OBSTRUCTION IN THE THEORY OF FOLIATIONS.

PMID- 16591129
TI  - A STOCHASTIC MODEL FOR THE INTERPRETATION OF CLINICAL TRIALS.

PMID- 16591130
TI  - ON DIFFERENTIAL SYSTEMS, II.

PMID- 16591131
TI  - THE ENERGY RATE-DEPTH FUNCTION FOR EARTHQUAKES.

PMID- 16591133
TI  - SPLINE INTERPOLATION AND THE HIGHER DERIVATIVES.

PMID- 16591132
TI  - THE INDEPENDENCE OF THE CONTINUUM HYPOTHESIS, II.

PMID- 16591134
TI  - THE BOWL THEOREM AND A MODEL NONDEGENERATE FUNCTION.

PMID- 16591135
TI  - LONG DISTANCE HOMING IN THE NEWT TARICHA RIVULARIS.

PMID- 16591136
TI  - STRAIN ELECTROMETRY AND PASSIVATION OF ALUMINUM ELECTRODES.

PMID- 16591137
TI  - THE TUNICATE LOCUS IN MAIZE DISSECTED AND RECONSTITUTED.

PMID- 16591138
TI  - FERTILITY OF TARICHA SPECIES-HYBRIDS AND VIABILITY OF THEIR OFFSPRING.

PMID- 16591140
TI  - INTERPOLATION OF GENERAL BOUNDED AND OF ALMOST PERIODIC SEQUENCES BY FUNCTIONS OF
      STRATIFIED EXPONENTIAL TYPE.

PMID- 16591139
TI  - MINIMIZATION OF SYSTEM COSTS IN TERMS OF SUBSYSTEM COSTS.

PMID- 16591141
TI  - ATTENUATION IN THE MANTLE AND RIGIDITY OF THE CORE FROM MULTIPLY REFLECTED CORE
      PHASES.

PMID- 16591142
TI  - A SOLVABLE CASE OF THE TRAVELING SALESMAN PROBLEM.

PMID- 16591143
TI  - ON DECOMPOSITIONS OF A RECTANGLE INTO TWO QUADRILATERALS.

PMID- 16591144
TI  - DIFFERENTIAL RATES OF DEVELOPMENT OF HETEROTIC AND NONHETEROTIC YOUNG MAIZE
      SEEDLINGS, I. CORRELATION OF DIFFERENTIAL MORPHOLOGICAL DEVELOPMENT WITH
      PHYSIOLOGICAL DIFFERENCES IN GERMINATING SEEDS.

PMID- 16591145
TI  - INFERENCES CONCERNING THE TERTIARY AMERICAN BIRD FAUNAS.

PMID- 16591146
TI  - COMPARATIVE EXPERIMENT AND OBSERVED ASSOCIATION.

PMID- 16591147
TI  - CORRELATION BETWEEN THE SIGNIFICANT LIQUID STRUCTURE THEORY AND THE CELL THEORY.

PMID- 16591148
TI  - THE PERFECT RELATIVISTIC GAS.

PMID- 16591149
TI  - MATERIAL MOMENTUM-ENERGY TENSORS AND THE CALCULUS OF VARIATIONS.

PMID- 16591150
TI  - ANALYTIC CONTINUATION AND THE SCHWARZ REFLECTION PRINCIPLE.

PMID- 16591151
TI  - SUFFICIENT CONDITIONS FOR THE VALIDITY OF CAUCHY'S INTEGRAL FORMULA.

PMID- 16591152
TI  - COMPACTIFICATIONS OF HOMOGENEOUS SPACES AND CONTRACTIONS OF LIE GROUPS.

PMID- 16591154
TI  - ON THE SIGNIFICANCE OF AVERAGE MOLECULAR WEIGHTS FROM SEDIMENTATION EQUILIBRIUM
      EXPERIMENTS.

PMID- 16591153
TI  - DIFFRACTION OF SCALAR ELASTIC WAVES BY A CLAMPED FINITE STRIP.

PMID- 16591155
TI  - COMPARATIVE EXPERIMENT AND OBSERVED ASSOCIATION, II.

PMID- 16591156
TI  - EIGENVALUES OF THE LAPLACE OPERATOR ON CERTAIN MANIFOLDS.

PMID- 16591157
TI  - TRANS-15,16-DIMETHYLDIHYDROPYRENE: A NEW TYPE OF AROMATIC SYSTEM HAVING METHYL
      GROUPS WITHIN THE CAVITY OF THE pi-ELECTRON CLOUD.

PMID- 16591158
TI  - IMMUNOCHEMICAL IDENTIFICATION OF THE ALDOBIURONIC ACID OF THE SLIME OF
      SPHAEROTILUS NATANS.

PMID- 16591159
TI  - COMMENT ON "SINGLE-PARTICLE CYCLOTRON RADIATION NEAR WALLS AND SHEATHS," BY A.
      SIMON AND M. N. ROSENBLUTH.

PMID- 16591160
TI  - DIFFRACTION OF SCALAR ELASTIC WAVES BY A FINITE CRACK.

PMID- 16591161
TI  - DIRECT PRODUCT BRANCHING PROCESSES AND RELATED MARKOV CHAINS.

PMID- 16591162
TI  - A SECOND HYBRID ENZYME IN MAIZE.

PMID- 16591163
TI  - A UNIFORM COHOMOLOGY THEORY FOR ALGEBRAS.

PMID- 16591164
TI  - QUANTUM CELL MODEL FOR HARD SPHERES.

PMID- 16591165
TI  - THE REAL K-THEORY OF CLASSIFYING SPACES.

PMID- 16591166
TI  - ON SEMI-MARKOV PROCESSES.

PMID- 16591167
TI  - THE ORDER OF ELECTRON SHELLS IN IONIZED ATOMS.

PMID- 16591168
TI  - IN SITU DETECTION AND ESTIMATION OF CHLOROPHYLL AND OTHER PIGMENTS-PRELIMINARY
      RESULTS.

PMID- 16591169
TI  - EVIDENCE FOR A COMET BELT BEYOND NEPTUNE.

PMID- 16591170
TI  - OUTLINE OF A THEORY OF THE UNIVERSE.

PMID- 16591171
TI  - AN ENERGY-MOMENTUM TENSOR FOR COLLAPSING STARS.

PMID- 16591173
TI  - EXTENSION OF QUASICONFORMAL MAPPINGS FROM TWO TO THREE DIMENSIONS.

PMID- 16591172
TI  - THE EFFECT OF BRANCHING AT C-1 ON THE BIOLOGICAL ACTIVITY OF ALCOHOLS.

PMID- 16591174
TI  - DECOMPOSITION OF VECTOR MEASURES.

PMID- 16591175
TI  - A REMARK ON A CONJECTURE OF C. L. SIEGEL.

PMID- 16591176
TI  - INTRODUCTION.

PMID- 16591177
TI  - INTRODUCTION.

PMID- 16591178
TI  - SYMMETRY AND CONSERVATION LAWS.

PMID- 16591179
TI  - ELEMENTARY PARTICLES.

PMID- 16591180
TI  - THE STRUCTURE OF NUCLEI.

PMID- 16591181
TI  - THE ARCHITECTURE OF MOLECULES.

PMID- 16591182
TI  - RADIAL DISCRETIZATION IN SPHERICAL GALAXIES.

PMID- 16591183
TI  - HORMONAL CONTROL OF ENZYME SYNTHESIS IN BARLEY ENDOSPERM.

PMID- 16591184
TI  - BEHAVIOR OF PLANTS UNDER EXTRATERRESTRIAL CONDITIONS: SEED GERMINATION IN
      ATMOSPHERES CONTAINING NITROGEN OXIDES.

PMID- 16591185
TI  - HYDROSTATIC PRESSURE AND OSMOTIC POTENTIAL IN LEAVES OF MANGROVES AND SOME OTHER
      PLANTS.

PMID- 16591186
TI  - THE ENVIRONMENTAL CONTROL OF INSULAR VARIATION IN BIRD SPECIES ABUNDANCE.

PMID- 16591187
TI  - NATIONAL ACADEMY OF SCIENCES.

PMID- 16591188
TI  - CHEMICAL CONTROL OF VASCULAR CAMBIUM INITIATION IN ISOLATED RADISH ROOTS.

PMID- 16591189
TI  - NEW EVIDENCE ON RIGIDITY IN THE EARTH'S CORE.

PMID- 16591190
TI  - MORSE THEORY AND STABILITY BY LIAPUNOV'S DIRECT METHOD.

PMID- 16591191
TI  - THE EVENNESS OF THE NUMBER OF EDGES OF A CONVEX POLYHEDRON.

PMID- 16591192
TI  - ON CONSISTENCY OF BAYES PROCEDURES.

PMID- 16591193
TI  - A NEW CASE OF CONVECTION IN THE PRESENCE OF COMBINED VERTICAL SALINITY AND
      TEMPERATURE GRADIENTS.

PMID- 16591194
TI  - ON THE DIFFERENTIAL EQUATIONS OF BRILLOUIN-WIGNER PERTURBATION THEORY.

PMID- 16591195
TI  - THE COLORS OF FIREFLY BIOLUMINESCENCE: ENZYME CONFIGURATION AND SPECIES
      SPECIFICITY.

PMID- 16591196
TI  - DIFFRACTION OF VECTOR ELASTIC WAVES BY A CLAMPED FINITE STRIP.

PMID- 16591197
TI  - STABLE BUNDLES AND UNITARY BUNDLES ON A COMPACT RIEMANN SURFACE.

PMID- 16591198
TI  - RELATIVE CYTOGENETIC EFFICIENCY OF MUONS AND pi- MESONS IN ZEA MAYS (L.).

PMID- 16591199
TI  - GENETIC STUDIES ON MUTANT ENZYMES IN MAIZE, V. IN VITRO INTERCONVERSION OF
      ALLELIC ISOZYMES.

PMID- 16591200
TI  - A POSSIBLE FUNCTIONING IN VIVO OF PLASTOCYANIN IN PHOTOSYNTHESIS AS REVEALED BY A
      LIGHT-INDUCED ABSORBANCE CHANGE.

PMID- 16591202
TI  - ON ELEMENT SYNTHESIS AND THE INTERPRETATION OF THE ABUNDANCES OF HEAVY NUCLIDES.

PMID- 16591201
TI  - INTEGRATED MAGNETIC AND SUPERCONDUCTIVE MEMORIES.

PMID- 16591203
TI  - THE SINGULARITY OF GAUSSIAN MEASURES IN FUNCTION SPACE.

PMID- 16591204
TI  - UPPER AND LOWER BOUNDS FOR RAYLEIGH-SCHRODINGER PERTURBATION ENERGIES.

PMID- 16591205
TI  - THE DEVELOPMENT OF DIFFERENTIAL PERMEABILITY IN ISOLATED STELES OF CORN ROOTS.

PMID- 16591206
TI  - INTRODUCTION.

PMID- 16591207
TI  - THE ORIGIN OF THE ELEMENTS.

PMID- 16591208
TI  - THE HISTORY OF STARS AND GALAXIES.

PMID- 16591209
TI  - THE HISTORY OF THE SOLAR SYSTEM.

PMID- 16591210
TI  - THE ORIGINS OF THE CONTINENTS, OCEANS, AND ATMOSPHERE.

PMID- 16591211
TI  - THE ORIGINS OF LIFE.

PMID- 16591212
TI  - INTENSITY-DEPENDENT ABSORPTION OF LIGHT.

PMID- 16591213
TI  - SPECIFICATION OF MATERIALS FOR THE RETARDATION OF EVAPORATION OF WATER-THE
      SPREADING OF HEXADECANOL MONOLAYERS.

PMID- 16591214
TI  - GREEN'S FUNCTIONS FOR ONE-VELOCITY NEUTRON TRANSPORT IN A ONE-DIMENSIONAL SLAB
      AND SPHERE.

PMID- 16591215
TI  - THE MINIMUM NUMBER OF INTERSECTIONS IN COMPLETE GRAPHS.

PMID- 16591217
TI  - DURATION OF THE QUATERNARY AND ITS SUBDIVISIONS.

PMID- 16591216
TI  - STRUCTURE OF THE CENTRAL COMPONENT OF CENTAURUS A.

PMID- 16591218
TI  - X-RAY ANALYSIS OF PREFERRED ORIENTATION OF QUARTZ CRYSTALS IN THREE LINEATED
      QUARTZITES.

PMID- 16591219
TI  - A TWO-QUANTASOME THEORY OF CHLOROPHYLL-a FLUORESCENCE IN GREEN PLANT
      PHOTOSYNTHESIS.

PMID- 16591220
TI  - BEHAVIOR OF SOLUTIONS OF A LINEAR DIFFERENTIAL EQUATION OF SECOND ORDER.

PMID- 16591221
TI  - DISCRETIZED STRUCTURE IN THE DISTRIBUTION OF CLUSTERS OF GALAXIES.

PMID- 16591222
TI  - ORGANIZATION IN A GAMETOPHYTE CALLUS OF LYCOPODIUM AND ITS MORPHOGENETIC
      IMPLICATIONS.

PMID- 16591223
TI  - H CLASSES OF HOLOMORPHIC FUNCTIONS IN TUBE DOMAINS.

PMID- 16591224
TI  - DIFFRACTION OF VECTOR ELASTIC WAVES BY A FINITE CRACK.

PMID- 16591225
TI  - A THEOREM ON THE ISOTROPY GROUPS OF A HYPERELASTIC MATERIAL.

PMID- 16591226
TI  - DRIFTING CONTINENTS AND LATE PALEOZOIC GEOGRAPHY.

PMID- 16591227
TI  - SIGNIFICANT STRUCTURE THEORY OF BINARY LIQUID MIXTURES: CARBON TETRACHLORIDE AND
      CYCLOHEXANE.

PMID- 16591228
TI  - EXTENDED HUCKEL THEORY AND MOLECULAR HARTREE-FOCK SCF THEORY.

PMID- 16591229
TI  - SECONDARY DEUTERIUM ISOTOPE EFFECTS IN SOLVOLYSES OF SMALL-RING COMPOUNDS.

PMID- 16591231
TI  - RANDOM POLYGONS DETERMINED BY RANDOM LINES IN A PLANE.

PMID- 16591230
TI  - SURPLUS FREE POLES OF APPROXIMATING RATIONAL FUNCTIONS.

PMID- 16591232
TI  - CONTINUOUS MAPPINGS OF ALMOST AUTOMORPHIC AND ALMOST PERIODIC FUNCTIONS.

PMID- 16591233
TI  - SPLINE FUNCTIONS AND THE PROBLEM OF GRADUATION.

PMID- 16591234
TI  - ION UPTAKE BY PLANT MITOCHONDRIA.

PMID- 16591235
TI  - ON GRAVITATIONAL COLLAPSE AND THE CREATION OF ENERGY.

PMID- 16591236
TI  - REQUIREMENT FOR THE SYNTHESIS OF DNA-LIKE RNA FOR GROWTH OF EXCISED PLANT TISSUE.

PMID- 16591237
TI  - SINGULARITIES IN SPATIALLY HOMOGENEOUS, DUST-FILLED COSMOLOGICAL MODELS.

PMID- 16591238
TI  - DISTAL FUNCTIONS.

PMID- 16591240
TI  - ON COMPACTNESS OF MAPPINGS.

PMID- 16591239
TI  - FUNDAMENTAL PROPERTIES OF GENERALIZED SPLINES.

PMID- 16591241
TI  - THE SINGULARITIES OF INTEGRABLE STRUCTURALLY STABLE PFAFFIAN FORMS.

PMID- 16591242
TI  - ICE VII, THE DENSEST FORM OF ICE.

PMID- 16591244
TI  - THE CONSTRUCTION OF FORMAL COHOMOLOGY SHEAVES.

PMID- 16591243
TI  - AN ELEMENTARY THEORY OF THE CATEGORY OF SETS.

PMID- 16591245
TI  - COORDINATES FOR THE QUANTUM-MECHANICAL THREE-BODY PROBLEM.

PMID- 16591246
TI  - FLUORESCENCE CHANGES IN PORPHYRIDIUM EXPOSED TO GREEN LIGHT OF DIFFERENT
      INTENSITY: A NEW EMISSION BAND AT 693 mmu AND ITS SIGNIFICANCE TO PHOTOSYNTHESIS.

PMID- 16591247
TI  - RNA METABOLISM IN PUPAE OF THE OAK SILKWORM, ANTHERAEA PERNYI: THE EFFECTS OF
      DIAPAUSE, DEVELOPMENT, AND INJURY.

PMID- 16591248
TI  - THE CYTOCHROMES OF CHLOROPLASTS.

PMID- 16591249
TI  - GALACTIC DISCRETIZATION AND THE FUTURE OF THE UNIVERSE.

PMID- 16591250
TI  - STUDIES OF THE CYCLIZATIONS OF AN O-(alpha-METHYLALLYL)PHENOL AND THE
      CORRESPONDING METHYL ETHER INDUCED BY ELECTROPHILIC REAGENTS.

PMID- 16591252
TI  - ON THE APPLICATION OF DYNAMIC PROGRAMING TO THE DETERMINATION OF OPTIMAL PLAY IN
      CHESS AND CHECKERS.

PMID- 16591251
TI  - REDESIGN OVERCOMPENSATION.

PMID- 16591253
TI  - ON THE SOLUTIONS OF LINEAR SECOND-ORDER DIFFERENTIAL EQUATIONS.

PMID- 16591254
TI  - ON THE PROPAGATION OF ENERGY IN A STRATIFIED GASEOUS MEDIUM.

PMID- 16591255
TI  - LIFTING DISKS AND CERTAIN LIGHT OPEN MAPPINGS.

PMID- 16591256
TI  - ON THE RELATION BETWEEN INTEGER AND NONINTEGER SOLUTIONS TO LINEAR PROGRAMS.

PMID- 16591257
TI  - FINITELY PRESENTED GROUP WHOSE WORD PROBLEM HAS THE SAME DEGREE AS THAT OF AN
      ARBITRARILY GIVEN THUE SYSTEM (AN APPLICATION OF METHODS OF BRITTON).

PMID- 16591258
TI  - HARMONIC FUNCTIONS WITH GIVEN VALUES AND MINIMUM NORMS IN RIEMANNIAN SPACES.

PMID- 16591259
TI  - A TCHEBYCHEFF-LIKE INEQUALITY FOR STOCHASTIC PROCESSES.

PMID- 16591260
TI  - HYDROGEN EXCHANGE STUDIES OF sRNA.

PMID- 16591262
TI  - THE ACTUAL MASS OF POTENTIAL ENERGY, A CORRECTION TO CLASSICAL RELATIVITY.

PMID- 16591261
TI  - CARBOXYPEPTIDASE A, II. THE THREE-DIMENSIONAL ELECTRON DENSITY MAP AT 6 A
      RESOLUTION.

PMID- 16591263
TI  - A GENERALIZATION OF THE LEBESGUE-BOCHNER-STIELTJES INTEGRAL AND A NEW APPROACH TO
      THE THEORY OF INTEGRATION.

PMID- 16591264
TI  - RESULTS ON FINITE SEMIGROUPS DERIVED FROM THE ALGEBRAIC THEORY OF MACHINES.

PMID- 16591265
TI  - LIAPUNOV FUNCTIONS FOR THE PROBLEM OF LUR'E.

PMID- 16591266
TI  - ISOLATION OF LARGE OLIGONUCLEOTIDE FRAGMENTS FROM THE ALANINE RNA.

PMID- 16591268
TI  - MAGNETIC CIRCULAR DICHROISM STUDIES: A PRELIMINARY REPORT.

PMID- 16591267
TI  - NUCLEAR QUADRUPOLE AND SPIN-ROTATION INTERACTION OF O IN FORMALDEHYDE.

PMID- 16591269
TI  - A NEW FINITE SIMPLE GROUP WITH ABELIAN 2-SYLOW SUBGROUPS.

PMID- 16591270
TI  - A FAMILY OF SPECTRAL OPERATIONS.

PMID- 16591271
TI  - A DIFFERENTIAL EQUATION FOR THE THETA FUNCTION.

PMID- 16591273
TI  - COMMUTATORS OF SINGULAR INTEGRAL OPERATORS.

PMID- 16591272
TI  - NONEMPIRICAL MOLECULAR ORBITAL THEORY FROM MOLECULAR HARTREE-FOCK THEORY.

PMID- 16591274
TI  - EXISTENCE OF PERIODIC SOLUTIONS FOR NONLINEAR EQUATIONS OF EVOLUTION.

PMID- 16591275
TI  - AN EXPERIMENTAL METHOD FOR DETERMINING A-VALUES: THE METHYL GROUP.

PMID- 16591276
TI  - INTRINSIC ANALYTIC CONTINUATION AND ENVELOPES OF HOLOMORPHY.

PMID- 16591277
TI  - ON THE IDENTIFICATION OF SYSTEMS AND THE UNSCRAMBLING OF DATA, I. HIDDEN
      PERIODICITIES.

PMID- 16591278
TI  - ON THE IDENTIFICATION OF SYSTEMS AND THE UNSCRAMBLING OF DATA, II. AN INVERSE
      PROBLEM IN RADIATIVE TRANSFER.

PMID- 16591279
TI  - ON CONTINUOUS MARTINGALES.

PMID- 16591280
TI  - A CONJECTURE ON CONFORMATIONS LEADING TO ENERGY TRAPPING IN HELICAL POLYMERS.

PMID- 16591281
TI  - ELECTRON MICROSCOPY OF THE GUNFLINT MICROFLORA: PRELIMINARY RESULTS.

PMID- 16591282
TI  - STATISTICAL MECHANICS AND IRREVERSIBILITY.

PMID- 16591283
TI  - QUANTUM CORRECTIONS TO THE EQUATION OF STATE FOR A STEEP REPULSIVE POTENTIAL.

PMID- 16591284
TI  - ON CHANDRASEKHAR'S LIMITING MASS FOR ROTATING WHITE DWARF STARS.

PMID- 16591285
TI  - SYNTHESIS OF SERUM PROTEINS BY A CELL-FREE SYSTEM FROM RAT LIVER.

PMID- 16591286
TI  - A GENERALIZATION OF CONVEXITY, AND MARTINGALES IN LINEAR SPACES.

PMID- 16591287
TI  - ON CROSS SECTIONS TO FIBER SPACES.

PMID- 16591288
TI  - EXISTENCE OF COMPLETE MINIMAL SURFACES OF ARBITRARY CONNECTIVITY AND GENUS.

PMID- 16591289
TI  - ON THE STABILITY OF SYSTEMS DEFINED OVER A FINITE TIME INTERVAL.

PMID- 16591290
TI  - RECONNAISSANCE OF THE SOMALI CURRENT DURING THE SOUTHWEST MONSOON.

PMID- 16591291
TI  - MAPPING THEOREMS FOR NONCOMPACT NONLINEAR OPERATORS IN BANACH SPACES.

PMID- 16591292
TI  - STOKES' THEOREM ON REAL ANALYTIC VARIETIES.

PMID- 16591293
TI  - CONVERGENCE PROPERTIES OF GENERALIZED SPLINES.

PMID- 16591294
TI  - INTEGRAL REPRESENTATION OF LINEAR CONTINUOUS OPERATORS FROM THE SPACE OF LEBESGUE
      BOCHNER SUMMABLE FUNCTIONS INTO ANY BANACH SPACE.

PMID- 16591295
TI  - A REMARK ON THE CENTRAL LIMIT THEOREM.

PMID- 16591296
TI  - DEFORMATIONAL KINKS IN BRUCITE AND GYPSUM.

PMID- 16591297
TI  - OSCILLATIONS OF THE EARTH: NEW CORE-MANTLE BOUNDARY MODEL BASED ON LOW-ORDER FREE
      VIBRATIONS.

PMID- 16591298
TI  - DYNAMIC VISCOELASTIC BEHAVIOR OF DILUTE PARAMYOSIN SOLUTIONS.

PMID- 16591300
TI  - FIXATION IMAGES OF SIEVE ELEMENT PLASTIDS IN BETA.

PMID- 16591299
TI  - CHEMICAL ENHANCEMENT OF SUPERCONDUCTIVITY.

PMID- 16591301
TI  - CARBON ASSIMILATION OF MARINE PHYTOPLANKTON IN ANTARCTICA.

PMID- 16591302
TI  - STRUCTURED COSMOLOGICAL MODELS.

PMID- 16591303
TI  - QUANTUM CHEMICAL STUDIES OF CHARGE-TRANSFER COMPLEXES OF INDOLES.

PMID- 16591304
TI  - THE FORMATION OF CONDENSED PHOSPHATE IN AQUEOUS SOLUTION.

PMID- 16591305
TI  - TWO METHODS FOR ESTIMATING COMPRESSION AND SOUND VELOCITY AT VERY HIGH PRESSURES.

PMID- 16591306
TI  - LOCALLY OPTIMAL TEST FOR HOMOGENEITY WITH RESPECT TO VERY RARE EVENTS.

PMID- 16591307
TI  - THE POWER GROUP OF TWO PERMUTATION GROUPS.

PMID- 16591308
TI  - A PROBLEM OF BING.

PMID- 16591309
TI  - DIRECTED FAMILIES OF SETS AND CLOSEDNESS OF FUNCTIONS.

PMID- 16591310
TI  - SHADOW SCATTERING AT LARGE ANGLES.

PMID- 16591311
TI  - FREE RADICALS FORMED BY HYDROGEN ATOM BOMBARDMENT OF THE NUCLEIC-ACID BASES.

PMID- 16591312
TI  - ON A NEW APPROACH TO THE NUMERICAL SOLUTION OF A CLASS OF PARTIAL DIFFERENTIAL
      INTEGRAL EQUATIONS OF TRANSPORT THEORY.

PMID- 16591313
TI  - ELECTRON SPIN RESONANCE OF FREE RADICALS IN PERHYDROTRIPHENYLENE INCLUSION
      COMPOUNDS.

PMID- 16591314
TI  - OCCURRENCE OF BIOGENIC STERANES AND PENTACYCLIC TRITERPANES IN AN EOCENE SHALE
      (52 MILLION YEARS) AND IN AN EARLY PRECAMBRIAN SHALE (2.7 BILLION YEARS): A
      PRELIMINARY REPORT.

PMID- 16591315
TI  - THE SIGNIFICANT STRUCTURE THEORY APPLIED TO META- AND PARA-XYLENE.

PMID- 16591316
TI  - SOME NEW METHODS FOR PLANETARY EXPLORATION.

PMID- 16591317
TI  - ABIOGENIC SYNTHESIS IN THE MARTIAN ENVIRONMENT.

PMID- 16591318
TI  - CONTINUITY OF MULTIFUNCTIONS.

PMID- 16591319
TI  - A NEW APPROACH TO THE NUMERICAL SOLUTION OF A CLASS OF LINEAR AND NONLINEAR
      INTEGRAL EQUATIONS OF FREDHOLM TYPE.

PMID- 16591320
TI  - ALGEBRAIC STRUCTURE OF LINEAR DYNAMICAL SYSTEMS, I. THE MODULE OF Sigma.

PMID- 16591321
TI  - ON THE GROUP OF CONFORMAL TRANSFORMATIONS OF A COMPACT RIEMANNIAN MANIFOLD.

PMID- 16591322
TI  - A GENERAL WEDDERBURN THEOREM.

PMID- 16591323
TI  - QUANTUM CORRECTIONS TO THE EQUATION OF STATE OF GASES AT HIGH TEMPERATURES AND
      DENSITIES.

PMID- 16591325
TI  - THE REDUCTION OF A FUNCTION NEAR A NONDEGENERATE CRITICAL POINT.

PMID- 16591324
TI  - THE USE OF HOT PHENOL IN PREPARING DNA.

PMID- 16591326
TI  - PLANAR GRAPHS AND RELATED TOPICS.

PMID- 16591327
TI  - On the spiral structure of disk galaxies, ii. Outline of a theory of density
      waves.

PMID- 16591329
TI  - COMPLEX STRUCTURES ON S x S.

PMID- 16591328
TI  - On the stress-strain relations for cubic crystals.

PMID- 16591330
TI  - Structure theory for a class of jordan algebras.

PMID- 16591331
TI  - Fundamental polyhedrons and limit point sets of kleinian groups.

PMID- 16591332
TI  - Investigation on groups of even order, ii.

PMID- 16591333
TI  - Shrinking a manifold in a manifold.

PMID- 16591334
TI  - On the culture of a microorganism similar to the precambrian microfossil
      kakabekia umbellata barghoorn in nh(3)-rich atmospheres.

PMID- 16591336
TI  - On the controllability of a nonlinear system.

PMID- 16591335
TI  - Observations concerning magnetoaerodynamic drag and shock standoff distance.

PMID- 16591337
TI  - On the symmetries of certain hyperelastic simple liquid crystals.

PMID- 16591338
TI  - On riemannian manifolds with constant scalar curvature admitting a conformal
      transformation group.

PMID- 16591339
TI  - Analogy between body force and inelastic strain gradient in cubic crystals and
      isotropic bodies.

PMID- 16591340
TI  - Recent advances in the prehistoric archaeology of formosa.

PMID- 16591341
TI  - Late pleistocene vegetation and climate in taiwan (formosa).

PMID- 16591342
TI  - PHOTOELECTRIC SPECTROPHOTOMETRY OF eta CARINAE.

PMID- 16591343
TI  - On the mathematical mechanism of phase transition.

PMID- 16591344
TI  - Further remarks on nonlinear p-compact operators in banach space.

PMID- 16591345
TI  - The classification of the complex primitive infinite pseudogroups.

PMID- 16591346
TI  - On the construction of division rings by the deformation of fields.

PMID- 16591347
TI  - Algebraic complexes applied to chemistry.

PMID- 16591348
TI  - Quantum corrections to the third and fourth virial coefficients using the 6:12
      potential.

PMID- 16591349
TI  - Apparent lunar activity: historical review.

PMID- 16591350
TI  - Longitudinal waves in cubic crystals.

PMID- 16591351
TI  - Significant structure theory of molecules having hindered intermolecular rotation
      in the condensed phases.

PMID- 16591352
TI  - The category of noetherian modules.

PMID- 16591353
TI  - Connectivity of peripherally continuous functions.

PMID- 16591354
TI  - Hyperfunctions and linear partial differential equations.

PMID- 16591355
TI  - The plemelj formulas with unrestricted approach, and the continuity of cauchy
      type integrals.

PMID- 16591356
TI  - The founder principle and competitive ability of tribolium.

PMID- 16591357
TI  - The residue calculus and some transcendental results in algebraic geometry, I.

PMID- 16591359
TI  - Connected-diagram expansion of transport coefficients, ii. Quantum gas obeying
      boltzmann statistics.

PMID- 16591358
TI  - Correlation of nuclear quadrupole coupling constants with molecular electronic
      structure using molecular orbital theory.

PMID- 16591360
TI  - Biochemical studies on adenovirus multiplication, xi. Evidence of a cytoplasmic
      site for the synthesis of viral-coded proteins.

PMID- 16591361
TI  - National academy of sciences.

PMID- 16591362
TI  - The dielectric constant of liquid water and various forms of ice according to
      significant structure theory.

PMID- 16591363
TI  - Studies in irreversible thermodynamics, vi.

PMID- 16591364
TI  - On the compact homogeneous minimal submanifolds.

PMID- 16591365
TI  - Interaction of nonallelic genes on cellular antigens in species hybrids of
      columbidae, iii. Further identification of interacting genes.

PMID- 16591366
TI  - A study of the optical rotation of lipids extracted from soils, sediments, and
      the orgueil carbonaceous meteorite.

PMID- 16591367
TI  - The effects of rotor deceleration on equilibrium sedimentation experiments.

PMID- 16591369
TI  - Some results on locally homogeneous complex manifolds.

PMID- 16591368
TI  - Whyburn'S conjecture for some differentiable maps.

PMID- 16591370
TI  - On a conjecture of marshall Hall.

PMID- 16591371
TI  - On the unification of the calculus of variations and the theory of monotone
      nonlinear operators in banach spaces.

PMID- 16591372
TI  - On the mechanism of action of adenosine 3',5' cyclophosphate.

PMID- 16591373
TI  - Role of cyclic-3',5'-amp in the response of adipose tissue to insulin.

PMID- 16591374
TI  - Probability generating functions of absolute difference of two random variables.

PMID- 16591375
TI  - Convergence rates for the central limit theorem.

PMID- 16591376
TI  - General necessary conditions for optimization problems.

PMID- 16591377
TI  - A general theory of jordan rings.

PMID- 16591378
TI  - Existence and approximation of solutions of nonlinear variational inequalities.

PMID- 16591379
TI  - On the creation of mass in an expanding universe.

PMID- 16591380
TI  - Interaction of hydrogen atoms and hydroxyl radicals with 5-halogen uracils.

PMID- 16591381
TI  - A convex approximant method for nonconvex extensions of geometric programming.

PMID- 16591382
TI  - Chemical trapping of a primary quantum conversion product in photosynthesis.

PMID- 16591383
TI  - Acid-base indicator properties of sulfonephthaleins and benzeins in acetonitrile.

PMID- 16591384
TI  - Magnetic circular dichroism studies, ii. Preliminary results with some aromatic
      compounds.

PMID- 16591385
TI  - Ozonolysis of "polymer-type" material in coal, kerogen and in the orgueil
      meteorite: a preliminary report.

PMID- 16591386
TI  - Some observations on the faraday effect.

PMID- 16591387
TI  - On volumes generating the same lebesgue-bochner integration.

PMID- 16591388
TI  - Approximation by polynomials: uniform convergence as implied by mean convergence,
      iii.

PMID- 16591389
TI  - The fire areas on santa rosa island, california.

PMID- 16591390
TI  - The genetic control of alcohol dehydrogenase in maize: gene duplication and
      repression.

PMID- 16591391
TI  - Manifestation of linear organization in molecules of pneumococcal transforming
      DNA.

PMID- 16591392
TI  - Heat conservation in tuna fish muscle.

PMID- 16591394
TI  - Solar variation, a weather element.

PMID- 16591393
TI  - Xylan synthesis from uridine-diphosphate-d-xylose by particulate preparations
      from immature corncobs.

PMID- 16591395
TI  - Gravitational waves and the creation of mass.

PMID- 16591396
TI  - On moulton's orbits in the restricted problem of three bodies.

PMID- 16591397
TI  - The structure and properties of graphite and boron nitride.

PMID- 16591398
TI  - The slow rates of solvolysis of endo-5,6-trimethylene-endo-(2 and 8)-norbornyl
      tosylates: steric hindrance to ionization and the foote-schleyer correlation.

PMID- 16591399
TI  - The binding of nicotinamide-adenine dinucleotide to yeast d-glyceraldehyde-3
      phosphate dehydrogenase: temperature-jump relaxation studies on the mechanism of
      an allosteric enzyme.

PMID- 16591400
TI  - Singular integral operators on a half-line.

PMID- 16591402
TI  - Baryon resonances as rotational States.

PMID- 16591401
TI  - Harmonic semifields.

PMID- 16591403
TI  - The fire areas on santa rosa island, california, ii.

PMID- 16591404
TI  - Behavioral assay procedures for transfer of learned behavior by brain extracts,
      ii.

PMID- 16591405
TI  - The effect of RNA on the recovery of spinal-sectioned carp (cyprinus carpio).

PMID- 16591406
TI  - A frame-shift mutation involving the addition of two base pairs in the lysozyme
      gene of phage t4.

PMID- 16591407
TI  - Precipitating antibody in human serum to an antigen present in cultured burkitt's
      lymphoma cells.

PMID- 16591408
TI  - The difference in contact inhibition of cell replication between normal cells and
      cells transformed by different carcinogens.

PMID- 16591409
TI  - Patterns of synthesis of DNA-like RNA in parts of developing frog embryos.

PMID- 16591410
TI  - Hormonal requirements for myogenesis of striated muscle in vitro: insulin and
      somatotropin.

PMID- 16591411
TI  - The initiation of protein synthesis in eggs of rana pipiens.

PMID- 16591412
TI  - Circular dichroism of visual pigments in the visible and ultraviolet spectral
      regions.

PMID- 16591413
TI  - Cytokinetic analysis of tumor growth.

PMID- 16591414
TI  - The effects of erythorbic Acid treatments on melanin synthesis and on the adult
      life span in Drosophila melanogaster: preliminary report.

PMID- 16591415
TI  - Studies of insulin crystals at low temperatures: effects on mosaic character and
      radiation sensitivity.

PMID- 16591416
TI  - Liver acetyl coa carboxylase: the dissociation-reassociation process and its
      relation to catalytic activity.

PMID- 16591417
TI  - Examination of the nucleohistone from mouse liver and intestine for RNA
      covalently linked to histone.

PMID- 16591418
TI  - The evolutionary origins of the immunoglobulins.

PMID- 16591419
TI  - Ribosome activation and polysome formation in vitro: requirement for ATP.

PMID- 16591420
TI  - The in vitro synthesis of a noninfectious complex containing biologically active
      viral RNA.

PMID- 16591421
TI  - The initiation of viral protein synthesis in e. Coli extracts.

PMID- 16591422
TI  - A ribosome-catalyzed reaction between N-formylmethionyl-trna and puromycin.

PMID- 16591423
TI  - Binding of hormone to tissue: the first step in polypeptide hormone action.

PMID- 16591424
TI  - The subunit structure of fructose 1,6-diphosphatase.

PMID- 16591425
TI  - Specific inactivation of pepsin by a diazo ketone.

PMID- 16591426
TI  - Regulation of L-isoleucine biosynthesis in the photosynthetic bacterium
      rhodospirillum rubrum.

PMID- 16591427
TI  - Protein conformation in cell membrane preparations as studied by optical rotatory
      dispersion and circular dichroism.

PMID- 16591428
TI  - Mitochondrial DNA from sheep heart.

PMID- 16591429
TI  - Bacteriophage-specific proteins in e. Coli infected with an RNA bacteriophage.

PMID- 16591430
TI  - Inactivation of phage c21 by various preparations from lipopolysaccharide of e.
      Coli k-12.

PMID- 16591431
TI  - Studies on biosynthesis of the linkage region of chondroitin sulfate-protein
      complex.

PMID- 16591432
TI  - Structural basis for inhibition of protein synthesis by emetine and cycloheximide
      based on an analogy between ipecac alkaloids and glutarimide antibiotics.

PMID- 16591433
TI  - Comparison of amino Acid polymerization in B. Subtilis and e. Coli cell-free
      systems; hybridization of their ribosomes.

PMID- 16591434
TI  - Infectious nucleic acids of e. Coli bacteriophages, ix. Sedimentation constants
      and strand integrity of infectious m12 phage replicative-form RNA.

PMID- 16591435
TI  - Isolation of the lac repressor.

PMID- 16591436
TI  - Studies on polynucleotides, lix. Further codon assignments from amino Acid
      incorporations directed by ribopolynucleotides containing repeating trinucleotide
      sequences.

PMID- 16591437
TI  - A class of markov processes associated with nonlinear parabolic equations.

PMID- 16591438
TI  - Probability generating functions and their iterates.

PMID- 16591439
TI  - MOLECULAR STRUCTURE OF m-B(10)Cl(10)C(2)H(2).

PMID- 16591440
TI  - Endomitosis and polyribosome formation.

PMID- 16591441
TI  - The nuclear energy revolution-1966.

PMID- 16591442
TI  - Spin-state-dependent hemoprotein ultraviolet-absorption bands.

PMID- 16591443
TI  - Faces of an integer polyhedron.

PMID- 16591444
TI  - Asymptotic normality of linear rank statistics under alternatives.

PMID- 16591445
TI  - More about the maximal ergodic lemma of brunel.

PMID- 16591446
TI  - On the littlewood-paley and lusin functions in higher dimensions.

PMID- 16591447
TI  - Completeness and function-theoretic degeneracy of riemannian spaces.

PMID- 16591449
TI  - Does gravity change with time?

PMID- 16591448
TI  - Nondegenerate real-valued differentiable functions.

PMID- 16591450
TI  - Positive-energy particle models with mass splitting.

PMID- 16591451
TI  - Heat transfer solely by molecular conduction in the metalimnion.

PMID- 16591453
TI  - ASYMPTOTIC THEORY OF ESTIMATES OF kTH-ORDER SPECTRA.

PMID- 16591452
TI  - Quasi-closed sets and fixed points.

PMID- 16591454
TI  - On the rigidity of hyperbolic space forms under quasi-conformal mappings.

PMID- 16591455
TI  - There is no tenth complex quadratic field with class-number one.

PMID- 16591456
TI  - Convolutions of vector fields and interpolation.

PMID- 16591457
TI  - Phase transition in a one-dimensional system.

PMID- 16591458
TI  - THE USE OF t-BUTYLCARBONIC DIETHYLPHOSPHORIC ANHYDRIDE FOR ACYLATING AMINES: A
      NEW WAY OF PREPARING, t-BUTOXYCARBONYL DERIVATIVES.

PMID- 16591459
TI  - The photoviscosity effect.

PMID- 16591460
TI  - THE ACTIVE SITE IN alpha-CHYMOTRYPSIN: METHYL 3,4-DIHYDROISOCOUMARIN-3
      CARBOXYLATE I.

PMID- 16591461
TI  - The effect of substituents on the hydrogen bonding of adenine and uracil
      derivatives.

PMID- 16591462
TI  - Neuronal dynamics and axonal flow, ii. The olfactory nerve as model test object.

PMID- 16591463
TI  - An ideal preparation of animals (on single-food-choice diet) for dissection of
      nerves and glands and for bone growth studies.

PMID- 16591464
TI  - The inhibition of splenic ribonuclease by liver cell extract.

PMID- 16591465
TI  - THE STRUCTURAL GENE FOR lambda EXONUCLEASE.

PMID- 16591466
TI  - in vitro MORPHOGENESIS OF PHAGE P22 FROM HEADS AND BASE-PLATE PARTS.

PMID- 16591467
TI  - Chromosome structure in phage t4, iii. Terminal redundancy and length
      determination.

PMID- 16591468
TI  - THE COMPLETE AMINO ACID SEQUENCE OF THE TRYPTOPHAN SYNTHETASE A PROTEIN (alpha
      SUBUNIT) AND ITS COLINEAR RELATIONSHIP WITH THE GENETIC MAP OF THE A GENE.

PMID- 16591469
TI  - Properties of hybrids between polyoma-transformed and normal mouse cells.

PMID- 16591470
TI  - ISOLATION OF THE lambda PHAGE REPRESSOR.

PMID- 16591471
TI  - Messenger RNA synthesis by a "coated" viral genome.

PMID- 16591472
TI  - MINIATURE escherichia coli CELLS DEFICIENT IN DNA.

PMID- 16591473
TI  - Cell size, nuclear content, and the development of polyploidy in the Mammalian
      liver.

PMID- 16591474
TI  - On the cooperativity of biological membranes.

PMID- 16591475
TI  - Initial homeward orientation after long-distance displacements in the newt
      taricha rivularis.

PMID- 16591476
TI  - Constitution of a compound with a pronounced juvenile hormone activity.

PMID- 16591477
TI  - Somatic recombination of duplicated genes: an hypothesis on the origin of
      antibody diversity.

PMID- 16591478
TI  - Identification of a tumor-specific determinant on neoplastic cell surfaces.

PMID- 16591479
TI  - ON THE MONOHEME NATURE OF CYTOCHROME c' (Rhodopseudomonas palustris).

PMID- 16591480
TI  - Inhibition of amino Acid transport in rat kidney cortex by puromycin.

PMID- 16591481
TI  - Prostatic nuclear chromatin: an effect of testosterone on the synthesis of
      ribonucleic Acid rich in cytidylyl(3',5')guanosine.

PMID- 16591483
TI  - Quantum requirement of the light-induced proton uptake by spinach chloroplasts.

PMID- 16591482
TI  - Translation of the genetic message, ii. Effect of initiation factors on the
      binding of formyl-methionyl-trna to ribosomes.

PMID- 16591484
TI  - Formation of imine bonds between transported sugars and lysyl residues of
      specific membrane proteins of erythrocytes and fat cells.

PMID- 16591485
TI  - The cytoplasmic synthesis of histones in hela cells and its temporal relationship
      to DNA replication.

PMID- 16591486
TI  - THE SYNTHESIS AND SECRETION OF gamma-GLOBULINS BY LYMPH NODE CELLS, I. THE
      MICROSOMAL COMPARTMENTALIZATION OF gamma-GLOBULINS.

PMID- 16591487
TI  - Single-stranded oligomers and polymers of cytidylic and 2'-deoxycytidylic acids:
      comparative optical rotatory studies.

PMID- 16591488
TI  - An altered pattern of RNA synthesis in serially propagated human diploid cells.

PMID- 16591489
TI  - The amino Acid sequence of spinach ferredoxin.

PMID- 16591490
TI  - Acetylcholinesterase, I. Large-scale purification, homogeneity, and amino Acid
      analysis.

PMID- 16591491
TI  - Mitochondrial transfer ribonucleic acids.

PMID- 16591492
TI  - Base-pairing configurations between purines and pyrimidines in the solid state: a
      2:1 crystalline complex containing 1-methyl-5-iodouracil and 9-ethyl-2,6
      diaminopurine.

PMID- 16591493
TI  - Concerning the mechanism of formation of uv-induced thymine photoproducts in DNA.

PMID- 16591494
TI  - The biosynthesis of insulin and a probable precursor of insulin by a human islet
      cell adenoma.

PMID- 16591495
TI  - Fine structure in fossil collagen.

PMID- 16591496
TI  - Solutions of gases in normal liquids.

PMID- 16591497
TI  - The structure of showdomycin, a novel carbon-linked nucleoside antibiotic related
      to uridine.

PMID- 16591498
TI  - The melting and pyrolysis of teflon and the melting of silver chloride and iodine
      under high pressure.

PMID- 16591499
TI  - A rotating cartesian-diver viscometer.

PMID- 16591500
TI  - On the nature of the hydrogen bond and the structure of water.

PMID- 16591501
TI  - On the inversion of the density gradient at the fringe of the convection zone.

PMID- 16591502
TI  - Probabilistic functions of finite-state markov chains.

PMID- 16591503
TI  - Jordan algebras of capacity two.

PMID- 16591504
TI  - Differential geometry of grassmann manifolds.

PMID- 16591505
TI  - The effects of juvenile hormone analogues on the embryonic development of
      silkworms.

PMID- 16591506
TI  - Temperature-dependent decay of RNA and of protein synthesis in a heat
      synchronized protozoan.

PMID- 16591507
TI  - MACRONUCLEAR DNA SYNTHESIS IN Stentor: REGULATION BY A CYTOPLASMIC INITIATOR.

PMID- 16591508
TI  - RETENTION OF MULTIPLE DEVELOPMENTAL POTENTIALITIES BY CELLS OF A MOUSE TESTICULAR
      TERATOCARCINOMA DURING PROLONGED CULTURE in vitro AND THEIR EXTINCTION UPON
      HYBRIDIZATION WITH CELLS OF PERMANENT LINES.

PMID- 16591509
TI  - The presence of antibodies in human serum to early (T) adenovirus antigens.

PMID- 16591510
TI  - A fluorochromatic test for immunocytotoxicity against tumor cells and leucocytes
      in agarose plates.

PMID- 16591511
TI  - Replication of poliovirus I in chick embryo and hamster cells exposed to sendai
      virus.

PMID- 16591512
TI  - FREQUENCY-DEPENDENT SELECTION AT THE ESTERASE 6 LOCUS IN Drosophila melanogaster.

PMID- 16591513
TI  - On the specificity of DNA polymerase.

PMID- 16591514
TI  - NONAUTONOMY IN DIFFERENTIATION OF PATTERN-DETERMINING GENES IN Drosophila, I. THE
      SEX COMB OF EYELESS-DOMINANT.

PMID- 16591516
TI  - The appearance of new species of RNA in the mouse spleen after immunization as
      detected by molecular hybridization.

PMID- 16591515
TI  - THE PHYSIOLOGICAL ROLE OF THE LYMPHOID SYSTEM, II. ERYTHROPHILIC gamma-GLOBULIN
      AND THE SURVIVAL OF THE ERYTHROCYTE.

PMID- 16591517
TI  - AUDITORY SENSITIVITY IN THE FAN-TOED GECKO, Ptyodactylus hasselquistii BOUTAN.

PMID- 16591518
TI  - Inferences from visual perception and reaction time to requisites for a collision
      preventing cyberlite stop lamp.

PMID- 16591519
TI  - Surface tension and the contraction of muscles.

PMID- 16591520
TI  - GENETIC CONTROL OF THE MEMBRANE PROTEIN COMPONENT OF THE LACTOSE TRANSPORT SYSTEM
      OF Escherichia coli.

PMID- 16591521
TI  - Binding properties and specificity of C-reactive protein.

PMID- 16591522
TI  - Antibodies to hapten-conjugated proteins which cross-react with RNA.

PMID- 16591523
TI  - POLYAMINES, RNA SYNTHESIS, AND STREPTOMYCIN LETHALITY IN A RELAXED MUTANT OF E.
      coli STRAIN 15 TAU.

PMID- 16591524
TI  - Translation of the genetic message, iii. Formylmethionine as initiator of
      proteins programed by polycistronic messenger RNA.

PMID- 16591525
TI  - The protein-synthetic lesion in unfertilized eggs.

PMID- 16591526
TI  - Modification of ribonucleic Acid synthesis in nuclei isolated from normal and
      regenerating liver: some effects of salt and specific divalent cations.

PMID- 16591527
TI  - Studies on polynucleotides, lxviii the primary structure of yeast phenylalanine
      transfer RNA.

PMID- 16591529
TI  - Bacitracin: an inhibitor of the dephosphorylation of lipid pyrophosphate, an
      intermediate in the biosynthesis of the peptidoglycan of bacterial cell walls.

PMID- 16591528
TI  - Role of guanosine 5'-triphosphate in the initiation of Peptide synthesis, I.
      Synthesis of formylmethionyl-puromycin.

PMID- 16591530
TI  - Characterization of cytoplasmic and chloroplast polysomes in plants: evidence for
      three classes of ribosomal RNA in nature.

PMID- 16591531
TI  - Enzymatic hydroxylation of proline and lysine in protocollagen.

PMID- 16591532
TI  - HYBRIDIZATION BETWEEN THE NUCLEAR AND KINETOPLAST DNA'S OF Leishmania enriettii
      AND BETWEEN NUCLEAR AND MITOCHONDRIAL DNA'S OF MOUSE LIVER.

PMID- 16591533
TI  - On the mechanism of electron transfer in complex iii of the electron transfer
      chain.

PMID- 16591534
TI  - Mechanism of viral carcinogenesis by DNA Mammalian viruses, ii. Viral-specific
      RNA in tumor cells induced by "weakly" oncogenic human adenoviruses.

PMID- 16591535
TI  - THE ABORTIVE REPLICATION OF PhiX174 DNA IN A RECOMBINATION-DEFICIENT MUTANT OF
      Escherichia coli.

PMID- 16591536
TI  - Preparation and properties of thymostatin, a new thymic inhibitor of DNA and RNA
      synthesis.

PMID- 16591537
TI  - Argininosuccinate synthetase activity and citrulline metabolism in cells cultured
      from a citrullinemic subject.

PMID- 16591538
TI  - A single amino Acid substitution (asparagine to aspartic Acid) between normal
      (b+) and the common negro variant (a+) of human glucose-6-phosphate
      dehydrogenase.

PMID- 16591539
TI  - Priming of DNA polymerase in nuclei of sea urchin embryos by native DNA.

PMID- 16591541
TI  - Virtual coulomb excitation in nucleon transfer.

PMID- 16591540
TI  - Stomata and the hydrologic cycle.

PMID- 16591542
TI  - Viscosity measurements of alcohol-water mixtures and the structure of water.

PMID- 16591543
TI  - On the rate with which a holomorphic function in a disk can tend radially to
      zero.

PMID- 16591544
TI  - E-points of games.

PMID- 16591545
TI  - Weak solutions of abstract differential equations.

PMID- 16591546
TI  - Interactions between superconductors and organic molecules.

PMID- 16591547
TI  - Faradaic rectification study of cadmium amalgam electrodes.

PMID- 16591548
TI  - A nuclear magnetic resonance study of water-ethanol mixtures.

PMID- 16591549
TI  - On visual hulls of sets.

PMID- 16591550
TI  - The decomposition of stable homotopy.

PMID- 16591551
TI  - Notes toward the construction of nonlinear relativistic quantum fields, I. The
      hamiltonian in two space-time dimensions as the generator of a C-automorphism
      group.

PMID- 16591552
TI  - Sufficient conditions for a family of probabilities to be exponential.

PMID- 16591553
TI  - Iterated logarithm inequalities.

PMID- 16591554
TI  - The analytic calculation of the index of elliptic equations.

PMID- 16591555
TI  - Theoretical effect of large hydrostatic pressures on the tensile strength of
      materials.

PMID- 16591556
TI  - Magnetic resonance of nitroxide probes in micelle-containing solutions.

PMID- 16591557
TI  - A single variable variational approximation for a perturbed schrodinger equation.

PMID- 16591558
TI  - Perturbation of eigenfunction expansions.

PMID- 16591559
TI  - General relativity theory of gravitation and experiments.

PMID- 16591560
TI  - Note on electric and magnetic polarization in moving media.

PMID- 16591561
TI  - Association of 1-1 salts in water.

PMID- 16591562
TI  - The hyperfine splitting of the interaction energy of two hydrogen atoms.

PMID- 16591564
TI  - Entropy, a complete metric invariant for automorphisms of the torus.

PMID- 16591563
TI  - On an improved partition function of significant structure theory.

PMID- 16591565
TI  - Inequalities for the sequence of sample means.

PMID- 16591566
TI  - A contribution to the theory of policy decisions.

PMID- 16591567
TI  - Effect of pressure on the ductility of solids.

PMID- 16591568
TI  - Electron spin resonance of an irradiated single crystal of Guanine hydrochloride
      dihydrate.

PMID- 16591569
TI  - Stereochemically nonrigid organometallic molecules, vii. Fluxional behavior of
      cyclooctatetraeneruthenium tricarbonyl.

PMID- 16591570
TI  - Ring opening and reclosure in a cyclic phosphorane.

PMID- 16591571
TI  - Introductory remarks.

PMID- 16591572
TI  - The iqsy and solar-terrestrial research.

PMID- 16591573
TI  - Radiations from the sun.

PMID- 16591574
TI  - Particles and fields in the interplanetary medium.

PMID- 16591575
TI  - Particles and fields in the magnetosphere.

PMID- 16591576
TI  - Developments in upper atmospheric science during the iqsy.

PMID- 16591577
TI  - Magnetic-moment evidence for the polyspheron structure of the lighter atomic
      nuclei.

PMID- 16591578
TI  - Thermal cosmic radiation and the formation of protogalaxies.

PMID- 16591579
TI  - Partly gentle perturbation with application to perturbation by annihilation
      creation operators.

PMID- 16591580
TI  - A noncompact dirichlet norm.

PMID- 16591581
TI  - Significant structure theory of isotope effect.

PMID- 16591582
TI  - Minimization of polypeptide energy, iii. Application of a rapid energy
      minimization technique to the calculation of preliminary structures of gramicidin
      s.

PMID- 16591583
TI  - Systematic analysis of chemical shifts in the nuclea magnetic resonance spectra
      of Peptide chains, I. Glycine-containing dipeptides.

PMID- 16591584
TI  - The structure of carboxypeptidase a, vi. Some results at 2.0-a resolution, and
      the complex with glycyl-tyrosine at 2.8-a resolution.

PMID- 16591585
TI  - The abundance of lead in the sun.

PMID- 16591586
TI  - CYTOKININS: SYNTHESIS OF 6-(3-METHYL-3-BUTENYLAMINO)-9-beta-D-RIBOFURANOSYLPURINE
      (3IPA), AND THE EFFECT OF SIDE-CHAIN UNSATURATION ON THE BIOLOGICAL ACTIVITY OF
      ISOPENTYLAMINOPURINES AND THEIR RIBOSIDES.

PMID- 16591587
TI  - Prebiotic porphyrin genesis: porphyrins from electric discharge in methane,
      ammonia, and water vapor.

PMID- 16591588
TI  - Organic geochemical studies, ii. A preliminary report on the distribution of
      aliphatic hydrocarbons in algae, in bacteria, and in a recent lake sediment.

PMID- 16591589
TI  - Structure of the photohydration products of cytidine and uridine.

PMID- 16591590
TI  - A two-structure model for electrolytic solutions.

PMID- 16591591
TI  - On the mechanism of thymine photodimerization.

PMID- 16591592
TI  - Relations between two kinds of theta constants on a riemann surface.

PMID- 16591593
TI  - Homogeneous complex manifolds and representations of semisimple lie groups.

PMID- 16591594
TI  - Souslin'S problem.

PMID- 16591595
TI  - A contribution to profit maximization.

PMID- 16591596
TI  - Dissipative processes, quantum States, and entropy.

PMID- 16591597
TI  - A challenge to the scientific community.

PMID- 16591598
TI  - Numerology of the constants of nature.

PMID- 16591599
TI  - An inerative procedure for the solution of perturbation equations.

PMID- 16591600
TI  - Fundamental equations of electrom agnetodynamics of fluids: various consequences.

PMID- 16591601
TI  - Spin-coupled wave functions for atoms and molecules.

PMID- 16591602
TI  - The surface tension of binary liquid mixtures.

PMID- 16591603
TI  - Retracting multifunctions.

PMID- 16591604
TI  - Ergodic theory and translation-invariant operators.

PMID- 16591605
TI  - A square integrability criterion for the cohomology of arithmetic groups.

PMID- 16591607
TI  - Subintegrals of set-valued functions with semianalytic graphs.

PMID- 16591606
TI  - On quasi-complemented subspaces of banach spaces.

PMID- 16591608
TI  - Some nonlinear networks capable of learning a spatial pattern of arbitrary
      complexity.

PMID- 16591609
TI  - On a new computing technique in optimal control theory and the maximum principle.

PMID- 16591610
TI  - A rapid photoreversible response of barley root tips in the presence of 3
      indoleacetic Acid.

PMID- 16591611
TI  - LIGHT-EMITTING MOLECULE IN A NEW PHOTOPROTEIN TYPE OF LUMINESCENCE SYSTEM FROM
      THE EUPHAUSID SHRIMP Meganyctiphanes norvegica.

PMID- 16591612
TI  - Photosynthetic phosphorylation as energy source for protein synthesis and carbon
      dioxide assimilation by chloroplasts.

PMID- 16591613
TI  - Theory of the physical characteristics of tensile fracture under pressure.

PMID- 16591614
TI  - Some new conditions for the strong law.

PMID- 16591616
TI  - Asymptotic normality of linear combinations of functions of order statistics, ii.

PMID- 16591615
TI  - Some consequences of the axiom of definable determinateness.

PMID- 16591617
TI  - On the jahn-teller effect in binuclear cu(ii) complexes.

PMID- 16591618
TI  - Entropy balance in photosynthesis.

PMID- 16591619
TI  - Theory of quantum-mechanical description.

PMID- 16591620
TI  - CHEMICAL INDUCTION OF HAPLOID FRUITING BODIES IN Schizophyllum commune.

PMID- 16591621
TI  - APOSPOROUS DIPLOID GAMETOPHYTES FROM SPOROPHYTES OF THE LIVERWORT Blasia pusilla
      L.

PMID- 16591622
TI  - Intramolecular hydrogen bonding of azo dyes in aqueous solution.

PMID- 16591623
TI  - Preferred orientation of quartz in a chert breccia.

PMID- 16591625
TI  - On the law of the iterated logarithm without assumptions about the existence of
      moments.

PMID- 16591624
TI  - Elliptic operators of higher order in divergence form.

PMID- 16591626
TI  - Decompositions of triply connected domains.

PMID- 16591627
TI  - An analysis of scientific productivity.

PMID- 16591628
TI  - CELL DIVISION AND THE DIFFERENTIATION OF WOUND-VESSEL MEMBERS IN CULTURED STEM
      SEGMENTS OF Coleus.

PMID- 16591629
TI  - MECHANISM OF MOVEMENTS OF GRANULES IN MELANOCYTES OF Fundulus heteroclitus.

PMID- 16591630
TI  - Phase transition in the sliding-filament model of muscular contraction.

PMID- 16591631
TI  - THE FUNCTION OF THE ACCESSORY SEX GLANDS IN Periplaneta americana (L.), I. A
      QUANTITATIVE BIOASSAY FOR THE JUVENILE HORMONE.

PMID- 16591632
TI  - Cytoplasmic particles carrying rapidly labeled RNA in developing insect
      epidermis.

PMID- 16591633
TI  - Size and structural variations of mitochondrial DNA.

PMID- 16591634
TI  - Studies on polynucleotides, lxxxiv. On the role of ribosomal subunits in protein
      synthesis.

PMID- 16591635
TI  - On stellar rotation.

PMID- 16591636
TI  - The resonating-valence-bond theory of superconductivity: crest superconductors
      and through superconductors.

PMID- 16591637
TI  - On the convergence of approximants to a markov chain, I.

PMID- 16591638
TI  - On generalized standard algebras.

PMID- 16591639
TI  - Sectional curvatures of grassmann manifolds.

PMID- 16591641
TI  - A trireticulate crystal structure: trihydrogen cobalticyanide and trisilver
      cobalticyanide.

PMID- 16591640
TI  - Theoretical distribution of two-dimensional projections in electron-microscopic
      sections.

PMID- 16591642
TI  - On the validity of the kirkwood-riseman theory.

PMID- 16591643
TI  - The significant structure theory applied to some liquid rocket fuels.

PMID- 16591644
TI  - The structure of a crystalline complex containing one phenobarbital molecule and
      two adenine derivatives.

PMID- 16591645
TI  - Influence of atmospheric stability layers on the effect of ground-based cloud
      seeding, I. Empirical results.

PMID- 16591646
TI  - Influence of atmospheric stability layers on the effect of ground-based cloud
      seeding, ii. Hypotheses in explanation.

PMID- 16591647
TI  - The nonimmersion problem for rp and higher-order cohomology operations.

PMID- 16591649
TI  - On the convergence of approximants to a markov chain, ii.

PMID- 16591648
TI  - Solution of the heawood map-coloring problem.

PMID- 16591650
TI  - Electron spin resonance of an irradiated single crystal of deoxyadenosine
      monohydrate.

PMID- 16591651
TI  - THE ELEMENTARY COMPOSITION OF Latimeria chalumnae SMITH.

PMID- 16591652
TI  - The biological and mechanical role of soil fungi.

PMID- 16591653
TI  - EXPERIMENTAL BIOLOGY OF AMMONIA-RICH ENVIRONMENTS: OPTICAL AND ISOTOPIC EVIDENCE
      FOR VITAL ACTIVITY IN Penicillium IN LIQUID AMMONIA-GLYCEROL MEDIA AT -40 degrees
      C.

PMID- 16591654
TI  - Planetary model for rapidly pulsating radio sources.

PMID- 16591655
TI  - Kinematic waves in the gulf stream.

PMID- 16591656
TI  - The time of appearance of cold water off somalia.

PMID- 16591657
TI  - Incompressibility at the earth's mantle-core boundary.

PMID- 16591658
TI  - Tensile strength of cubic crystals under pressure.

PMID- 16591659
TI  - Quantum-thermodynamic definition of electronegativity.

PMID- 16591660
TI  - Relaxation times for a hard-sphere gas.

PMID- 16591661
TI  - A "try simplest cases" resolution of the abraham-minkowski controversy on
      electromagnetic momentum in matter.

PMID- 16591662
TI  - Mycoplasma: SUSPECTED ETIOLOGIC AGENT OF CORN STUNT.

PMID- 16591663
TI  - The two juvenile hormones from the cecropia silk moth.

PMID- 16591664
TI  - Studies on the nature of messenger RNA in germinating wheat embryos.

PMID- 16591665
TI  - Introduction.

PMID- 16591666
TI  - Stress-strain relations for crystals containing plastic deformation.

PMID- 16591667
TI  - Momentum operators in quantum mechanics.

PMID- 16591668
TI  - How good is the born-oppenheimer approximation?

PMID- 16591669
TI  - Partial molar rotatory powers and optical activity in proteins and polypeptides,
      ii. The alpha-helix of poly-L-alanine.

PMID- 16591670
TI  - Conformations of polypeptides with ionized side chains of equal length.

PMID- 16591671
TI  - Application of a new modulation method for linear dichroism studies of oriented
      biopolymers in the vacuum ultraviolet.

PMID- 16591672
TI  - Ion distribution in concentrated electrolytes.

PMID- 16591673
TI  - A proton magnetic resonance study of the interaction of adenosine with
      polyuridylic Acid: evidence for both adenine-uracil base-stacking and base
      pairing.

PMID- 16591674
TI  - Natural-abundance C nuclear magnetic resonance spectra of medium-molecular-weight
      organic compounds.

PMID- 16591675
TI  - BOWLS, f-FIBER BUNDLES, AND THE ALTERATION OF CRITICAL VALUES.

PMID- 16591676
TI  - Convergence of poisson integrals for bounded symmetric domains.

PMID- 16591677
TI  - A kronecker-weyl theorem modulo 2.

PMID- 16591678
TI  - On complemented and quasi-complemented subspaces of quotients of c(s) for stonian
      s.

PMID- 16591679
TI  - On some functional equations associated with semigroups of operators.

PMID- 16591680
TI  - Some further remarks on inequalities for sample sums.

PMID- 16591681
TI  - Time-free continuous processes.

PMID- 16591682
TI  - On equations with sets as unknowns.

PMID- 16591683
TI  - The degree of convergence of sequences of linear positive operators.

PMID- 16591684
TI  - Extending the domain of the laplacian operator with the use of delta functions.

PMID- 16591685
TI  - Enzyme induction in embryonic retina: the role of transcription and translation.

PMID- 16591686
TI  - Circular dichroism spectra and the molecular arrangement of bacteriochlorophylls
      in the reaction centers of photosynthetic bacteria.

PMID- 16591687
TI  - Random numbers fall mainly in the planes.

PMID- 16591688
TI  - Chlorophyll energy levels and electron flow in photosynthesis.

PMID- 16591689
TI  - Temperature dependence of intersystem crossing: lifetime and intensity of so(2)
      phosphorescence in low-temperature solids.

PMID- 16591690
TI  - A possible relation between cosmological quantities and the characteristics of
      elementary particles.

PMID- 16591691
TI  - Correspondence of liquid and gaseous metals.

PMID- 16591692
TI  - Optimality and strong stability of control systems.

PMID- 16591693
TI  - Iteration and recursion.

PMID- 16591694
TI  - Cut points in general topological spaces.

PMID- 16591695
TI  - Nonlinear monotone and accretive operators in banach spaces.

PMID- 16591696
TI  - Determination of a for the simple flexible algebras.

PMID- 16591697
TI  - A perfect group of order 8,315,553,613,086,720,000 and the sporadic simple
      groups.

PMID- 16591698
TI  - HIGH-PRESSURE MOSSBAUER RESONANCE STUDIES OF THE CONVERSION OF Fe(III) TO Fe(II)
      IN FERRIC HALIDES.

PMID- 16591699
TI  - The crystal and molecular structure of the potassium salt of 2,2,5,5-tetramethyl
      3-carboxypyrroline-1-oxyl.

PMID- 16591700
TI  - The determination of intermolecular potentials from crystal data, I. General
      theory and application to crystalline benzene at several temperatures.

PMID- 16591701
TI  - The dual mechanisms of alkali cation absorption by plant cells: their parallel
      operation across the plasmalemma.

PMID- 16591702
TI  - Microspectrophotometric evidence for phytochrome in plant nuclei.

PMID- 16591703
TI  - THE INDUCTION OF delta-AMINOLEVULINIC ACID SYNTHETASE in vivo IN CHICK EMBRYO
      LIVER BY NATURAL STEROIDS.

PMID- 16591704
TI  - A THREE-CELL INTERACTION REQUIRED FOR THE INDUCTION OF THE PRIMARY IMMUNE
      RESPONSE in vitro.

PMID- 16591705
TI  - SUPERCONDUCTIVITY OF NB(3)(AL, GE) ABOVE 20.5 degrees K.

PMID- 16591706
TI  - Low-temperature studies on phytochrome: light and dark reactions in the red to
      far-red transformation and new intermediate forms of phytochrome.

PMID- 16591707
TI  - Microbiotas of the banded iron formations.

PMID- 16591708
TI  - Ocean bottom photographs in the area of the oldest known outcrops, north atlantic
      ocean.

PMID- 16591709
TI  - Optimality criteria in structural design.

PMID- 16591710
TI  - Meromorphic functions, covering properties, and cluster sets.

PMID- 16591712
TI  - An inequality for the hilbert transform.

PMID- 16591711
TI  - Some nonparametric sequential tests with power one.

PMID- 16591713
TI  - The effect of pressure on the oxidation state of iron, ii. Oxygen ligands.

PMID- 16591714
TI  - On the limitation of brood size in passerine birds by the ability of adults to
      nourish their young.

PMID- 16591715
TI  - Mating frequency in natural population of skippers and butterflies as determined
      by spermatophore counts.

PMID- 16591716
TI  - The significant structure theory of liquids applied to the shock compression of
      argon.

PMID- 16591717
TI  - Addition compounds of water and phenols.

PMID- 16591718
TI  - Remarks on a stopping time.

PMID- 16591719
TI  - Orders of convergence of the rayleigh-ritz and weinstein-bazley methods.

PMID- 16591720
TI  - On probabilities of large deviations.

PMID- 16591721
TI  - THE LIMITING DISTRIBUTION OF THE LAST TIME s(n) >/= nin.

PMID- 16591722
TI  - Characters of the discrete series of representations of sl(2) over a local field.

PMID- 16591723
TI  - Simplicial approximation of fixed points.

PMID- 16591724
TI  - On the structure of a gene for disease resistance in maize.

PMID- 16591725
TI  - Nuclear gene control of mitochondrial malic dehydrogenase in maize.
AB  - The isozymes of malic dehydrogenase (MDH) of maize have been separated by starch
      gel zone electrophoresis. The MDH isozyme pattern was the same in different
      organs and developmental stages. The subcellular distribution of the different
      isozymes was established by means of differential centrifugation. The MDH
      isozymes were found to be differentially distributed in the cytoplasm, the
      mitochondria, and the glyoxysomes. The latter proved the only exception to the
      pattern constancy among organs insofar as they are present only in the scutella.
      Among several inbred maize strains examined, only variants of the mitochondrial
      isozymes were found. Crosses between strains with different isozyme patterns gave
      Mendelian inheritance: thus, these mitochondrial isozymes are under nuclear-gene
      control.

PMID- 16591726
TI  - Probability distributions related to the law of the iterated logarithm.
AB  - Let W(t) denote a standard Wiener process for 0 </= t < infinity. We compute the
      probability that W(t) >/= t((1/2))A(t) for some t >/= 1 (or for some t >/= 0) for
      a certain class of functions A(t), including functions which are approximately (2
      log log t)((1/2)) as t --> infinity. We also give an invariance principle which
      states that this probability is the limit as m --> infinity of the probability
      that s(n) >/= n((1/2))A(n/m) for some n >/= m (or for some n >/= 1), where s(n)
      is the sum of n independent and identically distributed random variables with
      mean 0 and variance 1.

PMID- 16591727
TI  - Differences in leucyl-transfer rna's and synthetase in soybean seedlings.
AB  - Charged leucyl-transfer RNA (leucyl-tRNA) of soybean cotyledons can be
      fractionated into six radioactive peaks on a Freon column. Four leucyl-tRNA peaks
      are observed with the homologous hypocotyl system. Hypocotyl synthetase
      preparations only slightly acylate the other two leucyl-tRNA's (species 5 and 6).
      Further, leucyl-tRNA(5 and 6) of the hypocotyl are present in small amounts in
      comparison to the cotyledon. Therefore, the rate-limiting quantities of
      synthetase and tRNA(5 and 6) obtained from the hypocotyl prevent the detection of
      these two species of tRNA when a homologous hypocotyl system is used. To measure
      the relative amounts of hypocotyl tRNA's, the cotyledon synthetase preparation is
      employed. Preliminary results show that 6-benzyladenine increases the acylation
      of leucyl-tRNA(5 and 6) and decreases acylation of tRNA(1) in the hypocotyl.
      Synthetase preparations from cytokinin-treated plants are not significantly
      affected.

PMID- 16591728
TI  - The effect of pressure on the oxidation state of iron, iv. Thiocyanate and
      isothiocyanate ligands.
AB  - The effect of pressure on the Mossbauer resonance spectra of Fe(III) with
      thiocyanate (M-SCN) and isothiocyanate (M-NCS) ligands has been studied.
      Fe(NCS)(3).6H(2)O, which has the isothiocyanate structure, reduces with
      increasing pressure, reversibly, and with a pressure dependence for the
      conversion very similar to that shown by a wide variety of ionic ferric
      compounds. K(3)Fe(SCN)(6) has the thiocyanate structure. At low pressures, it
      exhibits a significantly larger reduction than the Fe(NCS)(3). With increasing
      pressure the thiocyanate complexes isomerize, each complex apparently exhibiting
      about the same degree of conversion at a given pressure. At 150 kb the
      isomerization is essentially complete. The reduction of the Fe(III) to Fe(II) is
      reversible but the isomerization is not, and the sample, when powdered and
      reloaded in the high-pressure cell, exhibits the isomer shift, quadrupole
      splitting, and Fe(III) to Fe(II) conversion characteristic of an isothiocyanate.
      Heating the thiocyanate to 110 degrees C at 5 kb yields a mixture of thiocyanate
      and isothiocyanate that converts with pressure completely to the isothiocyanate.

PMID- 16591729
TI  - Cyclic oxonium ions and related structures.
AB  - This paper describes the preparation by several methods of trialkyloxonium ions
      containing five-membered rings and the study of their structures by observing the
      nuclear magnetic resonance (NMR) spectra in several solvents. This provides
      independent evidence for these compounds, whose existence has been shown by
      kinetic, preparative, and stereochemical studies.The following SbCl(6) oxonium
      salts have been prepared, isolated, and characterized as crystalline solids: the
      1,2,5-trimethyltetrahydrofuranium (IIa), the 1,2,2,5-tetramethyl (IIb), the trans
      1-methylperhydrobenzofuranium (IVa), the trans-1,2-dimethyl (IVb), and the trans
      1,2,2-trimethyl (IVc) compounds. The trifluoroacetate salts IIc, IId, IVd, and
      IVe have been made in acid solution, and all the salts II and IV have been
      characterized by their NMR spectra as cyclic oxonium salts, with the charged 1
      CH(3) group downfield from an uncharged -OCH(3). Spectra of all the SbCl(6) salts
      in nitrobenzene solution are reported. Further evidence for the cyclic structure
      is given by the identification of 2,2,5-trimethyltetrahydrofuran (VIII) from the
      action of pyridine and lithium chloride on the 1,2,2,5
      tetramethyltetrahydrofuranium salt IIb. Solvolysis of this salt by ethanol gave 2
      ethoxy-2-methyl-5-methoxyhexane (VII) by attack at the tertiary carbon of the
      oxonium ion. The structure of VII was established by its synthesis and that of
      the other possible isomer. The trifluoroacetate oxonium ion (IVe) gave, after
      three days in 5 per cent sulfuric-trifluoroacetic acid, trans-2,2
      dimethylperhydrobenzofuran and methyl trifluoroacetate.

PMID- 16591731
TI  - On the Thomas-fermi equation.
AB  - A study has been made of some mathematical aspects of the Thomas-Fermi equation.
      This is a preliminary report on the results obtained, including (1) convergence
      of relevant series, (2) existence of unbounded solutions, (3) existence of
      solutions having an arbitrary branch point, (4) determination of a class of
      solutions bounded for large values of the variable, and (5) determination of a
      class of solutions unbounded for small values.

PMID- 16591730
TI  - A new chroococcacean alga from the proterozoic of queensland.
AB  - Nannofossils section sign here described are from the middle Proterozoic Paradise
      Creek Formation, along Paradise Creek in northwestern Queensland, Australia.
      These fossils, in chert blebs associated with branched stromatolites, comprise
      cubic colonies analogous to living Eucapsis, a member of the blue-green algal
      family Chroococcaceae. The age of the enclosing rocks, bracketed by the ages of
      older and younger granitic events, is about 1.6 x 10(9) years. We record,
      therefore, a new chronological and biological datum in the currently accumulating
      sequence of pre-Paleozoic microbiotas.

PMID- 16591732
TI  - Proterozoic eucaryotes from eastern california.
AB  - Both procaryotic and eucaryotic nannofossils occur in chert from the upper Beck
      Spring Dolomite (Pahrump Group) in northeastern San Bernardino County,
      California. These fossils include the oldest reasonably certain records to date
      of chlorophycean and chrysophycean algae, and hence of the eucaryotic or mitosing
      cell. Associated with these are cyanophycean procaryotes of still more ancient
      affinities. Indirect radiometric evidence implies an age of 1.2 to 1.4 aeons (1.2
      to 1.4 x 10(9) years) for the enclosing rocks. Associated stromatolites are
      consistent with such an age assignment.

PMID- 16591733
TI  - Fatigue crack nucleation in metals.
AB  - One of the unanswered questions in the study of fatigue is how cracks nucleate at
      stresses far below the static fracture strength. Previous theories show possible
      qualitative mechanisms that may operate in a crystal at room and low temperatures
      but none provides a quantitiative theory of this phenomenon. We show here a
      quantitative mechanism of fatigue crack initiation.With a small initial stress
      field, two closely located thin slices slide in opposite directions under cyclic
      loading. The increase of the local plastic strain with cycles of loading is
      calculated. The local plastic shear strain, positive in one slice and negative in
      the other, reaches 100 per cent at the free surface in a few hundred cycles.
      These large strains clearly cause the start of an extrusion or intrusion and
      fatigue crack nucleation.

PMID- 16591735
TI  - THE DIFFERENTIABILITY OF THE RIEMANN FUNCTION AT CERTAIN RATIONAL MULTIPLES OF
      pi.
AB  - It is shown that a continuous function which Riemann is said to have believed to
      be nowhere differentiable is in fact differentiable at certain points.

PMID- 16591734
TI  - Flexibility of supposed "rigid" molecules: substituted 2,5-piperazinediones
      (diketopiperazines).
AB  - The relevant results of accurate X-ray analyses of both the trans-and the L-cis
      3,6-dimethyl-2,5-piperazinediones (diketopiperazines) are reported. We note that
      a large variability of conformations for the ring system can be accomplished by
      coupling small bond-angle deformations with large variations of the internal
      rotation angles. The experimental molecular models are discussed in terms of
      these changes and in terms of nonbonded intramolecular interactions.

PMID- 16591736
TI  - The radical of a jordan algebra.
AB  - In this paper we define a Jacobson radical for Jordan algebras analogous to that
      for associative algebras and show that it enjoys many of the properties of the
      associative radical. We then relate the corresponding notion of "semisimplicity"
      to the previously defined notion of "nondegeneracy" (Jacobson, N., these
      Proceedings, 55, 243-251 (1966)).

PMID- 16591737
TI  - Two kinds of theta constants and period relations on a riemann surface.
AB  - It was recognized in Riemann's work more than one hundred years ago and proved
      recently by Rauch (cf. Bull. Am. Math. Soc., 71, 1-39 (1965) that the g(g + 1)/2
      unnormalized periods of the normal differentials of first kind on a compact
      Riemann surface S of genus g >/= 2 with respect to a canonical homology basis are
      holomorphic functions of 3g - 3 complex variables, "the" moduli, which
      parametrize the space of Riemann surfaces near S and, hence, that there are (g -
      2)(g - 3)/2 holomorphic relations among those periods. Eighty years ago, Schottky
      exhibited the one relation for g = 4 as the vanishing of an explicit homogeneous
      polynomial in the Riemann theta constants. Sixty years ago, Schottky and Jung
      conjectured a result which implies Schottky's earlier one and some
      generalizations for higher genera.Here, we formulate Schottky and Jung's
      conjecture precisely and, on the basis of a recent result of Farkas (these
      PROCEEDINGS, 62, 320 (1969)), prove it. We then derive Schottky's result (we
      believe for the first time correctly) and exhibit a typical relation of this kind
      for g = 5 (we can do this for any genus). We do not prove that our relations
      imply all relations, but there are some indications that they do.

PMID- 16591738
TI  - Fake tori, the annulus conjecture, and the conjectures of kirby.
AB  - The main result of this note (Theorem A) is that the set of piecewise linear
      (P.L.) manifolds of the same homotopy type as the n-torus, T(n), n >/= 5, is in
      one-to-one correspondence with the orbits of A(n-3)(pi(1)T(n)) [unk] Z(2) under
      the natural action of the automorphism group of pi(1)T(n). Every homotopy torus
      has a finite cover P.L. homeomorphic to T(n); hence the generalized annulus
      conjecture holds in dimension >/=5 (Kirby, R. C., "Stable homeomorphisms,"
      manuscript in preparation). The methods of this classification are also used to
      study some conjectures of R. C. Kirby (manuscript in preparation) related to
      triangulating manifolds.

PMID- 16591739
TI  - Total synthesis of the racemic form of the second juvenile hormone (methyl 12
      homojuvenate) from the cecropia silk moth.
AB  - Methyl cis-10-epoxy-3,7,11-trimethyl-trans,trans-2,6-tridecadienoate has been
      stereoselectively synthesized in 12 steps starting from methyl trans-gamma-bromo
      beta,beta-dimethylacrylate and 1-acetyl-1-methylcyclopropane. The final product
      proved to be identical with the second, less abundant juvenile hormone (methyl 12
      homojuvenate) isolated from the Cecropia silk moth. The biological activities of
      the compound were evaluated in various insects.

PMID- 16591740
TI  - Translation operators on the half-line.
AB  - The self-adjoint algebra of operators generated by the semigroup of translation
      operators acting on the Hilbert space of functions supported on the half-line is
      studied. A real-valued index is introduced and is used to determine the spectrum
      of the Wiener-Hopf integral operators with distribution kernel having an almost
      periodic Fourier transform. Further, the algebra is shown to contain no nonzero
      compact operators, and the quotient of the algebra by its commutator ideal is
      shown to be isometrically isomorphic to the Banach algebra of almost periodic
      functions on the line.

PMID- 16591741
TI  - Schwarz'S lemma in normed linear spaces.
AB  - In this paper we show that any Frechet holomorphic function mapping the open unit
      ball of one normed linear space into the closed unit ball of another must be a
      linear mapping if the Frechet derivative of the function at zero is a surjective
      isometry. From this fact we deduce a Banach-Stone theorem for operator algebras
      which generalizes that of R. V. Kadison.

PMID- 16591742
TI  - Interference of moonlight with the photoperiodic measurement of time by plants,
      and their adaptive reaction.
AB  - Threshold values of photoperiodic time-measurements correspond approximately to
      moonlight intensities. Experiments with Glycine and Euglena reveal that this is
      also the threshold value for synchronization of the circadian cycle. Saturation
      of this reaction is reached with 10 lx in 12:12 hr light-dark cycles. Thus,
      moonlight might disturb time measurement.In Glycine, Arachis, and Trifolium the
      intensity of the light coming from the moon to the upper surface of the leaf is
      reduced by circadian leaf movement to values between 5 and 20 per cent (or even
      less than 5 per cent) of full-moon light intensity. Such a reduction eliminates
      the disturbing effects of moonlight. This finding indicates that leaf movements
      have an adaptive value of the kind that Darwin sought to identify. It also
      indicates that the behavior of the upper leaf epidermis as a "sense organ for
      light"(13) has an adaptive value.In the short-day plants Perilla ocymoides and
      Chenopodium amaranticolor, a specific photoperiodic phenomenon was found that
      counteracts the disturbing effect of moonlight. Here light intensities similar to
      those of moonlight, introduced during the night, promote flowering instead of
      inhibiting it.

PMID- 16591743
TI  - Developmental phases of the biocoenosis.
AB  - Species number and diversity increase log-linearly with time during the early
      development of a biocoenosis. This period may be divided into three phases. In
      the first phase, diversity increases with the rapid immigration of species into
      the newly established habitat. In the second phase, diversity increases as common
      species become less common and rare species less rare. This period ends with the
      attainment of a maximum diversity pattern. In the third phase, rare species
      continue to invade the habitat until it is saturated. In each phase there is a
      maximal number of species that can invade the habitat.

PMID- 16591744
TI  - Motion of steroid spin labels in membranes.
AB  - Steroid spin labels have been found to undergo rapid and sometimes anisotropic
      rotational motion in membranes and phospholipid vesicle preparations. N-oxyl
      4',4'-dimethyloxazolidine derivatives of 5alpha-androstan-3-one-17beta-ol, 5beta
      androstan-3-one-17beta-ol, and 5alpha-androstan-3-one were prepared according to
      the procedure described by Keana. The paramagnetic five-membered ring is rigidly
      attached to the steroid nucleus at the 3-position, and thus the resonance
      spectrum of the nitroxide group reflects the motion of the entire steroid
      nucleus. This rapid motion, with rotational diffusion frequencies of the order of
      10(7) to 10(8) second(-1) is considered to lend plausibility to models of
      membrane transport involving rotations and/or translations of carriers within the
      hydrophobic region of the membrane. The steroid spin labels also form a
      convenient class of probes for studying conformational changes in membranes,
      since (a) their resonance spectra often fall in the category of "intermediate
      immobilization," which is most sensitive to small changes, and (b) these labels
      are quite soluble in a wide variety of membranes.

PMID- 16591746
TI  - Scientific program and abstracts of contributed papers.

PMID- 16591745
TI  - Cytokinins: synthesis, mass spectra, and biological activity of compounds related
      to zeatin.
AB  - Compounds related to dihydrozeatin that define the influence of the location of
      the hydroxyl group along the side chain have been synthesized and tested for
      cytokinin activity. The compounds compared are in the series: 6-(X-hydroxy-3
      methylbutylamino)purines and their ribosides, where X = 2, 3, and 4.Hydroxy
      substitution on the 4-position of the side chain enhances, but in the 2-, 3-, or
      2- and 3- positions, decreases cytokinin activity as compared with the
      unsubstituted isopentyl (or isopentenyl) chains. This differential influence of
      the position of the hydroxyl group in the N(6)-chain holds also for the similarly
      related 9-beta-D-ribofuranosides. The relatively higher activity of 3,4-dihydroxy
      as compared with 2,3-dihydroxy derivatives is consistent with this position
      effect.Compounds related to zeatin possessing side-chain ester moieties have also
      been synthesized and tested comparatively. Among these, 6-(4-acetoxy-3-methyl
      trans-2-butenylamino)purine is at least as active as zeatin, the most active
      presently known cytokinin in the tobacco bioassay, whereas the analog, methyl 2
      methyl-4-(purin-6-ylamino)-trans-crotonate, with the ester function effectively
      reversed, has vastly lower activity, and its riboside is practically inactive.

PMID- 16591747
TI  - Dependence of the kinetics of singlet-singlet energy transfer on spectral
      overlap.
AB  - Electronic excitation energy can be transferred between chromophores separated by
      distances of the order of 30 A. Forster proposed that the transfer occurs by a
      dipole-dipole resonance interaction which depends on certain spectroscopic and
      geometric properties of the donor-acceptor pair. His prediction that the rate of
      transfer depends on the inverse sixth power of the distance between the
      chromophores was verified previously. In this work, we tested a second prediction
      of Forster's theory, namely, that the transfer rate is proportional to J, the
      magnitude of the overlap between the emission spectrum of the energy donor and
      the absorption spectrum of the energy acceptor.The energy donor was an N
      methylindole moiety, and the acceptor was a ketone. These chromophores were fused
      to a rigid steroid that separated them by 10.2 A. Rate constants for singlet
      singlet energy transfer in this system were obtained by nanosecond flash
      spectroscopy. J was varied over a 40-fold range simply by altering the solvent.
      We found that the transfer rate is proportional to J, as predicted by Forster's
      theory. The results bear on the potential use of this energy transfer process to
      measure distances in biological macromolecules. It is evident that the length of
      such a spectroscopic ruler can readily be controlled by varying the magnitude of
      the spectral overlap integral of the energy donor-acceptor pair.

PMID- 16591748
TI  - A stationary state approach to radiationless transitions: radiation bandwidth
      effect on excitation processes in polyatomic molecules.
AB  - Excitation processes associated with photon absorption by a molecule are
      considered in terms of the stationary states of the molecule and the bandwidth of
      the incident radiation. The conditions of validity of the usual interpretation
      that transitions occur to excited Born-Oppenheimer states followed by
      radiationless transitions to other B-O states are examined in terms of the
      various correlation and relaxation times of the system. In contrast to the usual
      case, for sufficiently narrow radiation bandwidths, it is demonstrated that
      excitation should be regarded as occuring to molecular stationary states.

PMID- 16591749
TI  - A curvilinear extension of the maximum modulus principle.
AB  - The classical maximum principle is extended to the case where at frontier points
      the assumed global upper limit of the function is replaced by an upper limit
      along merely an arc, provided that the function does not have infinity as an
      asymptotic value.

PMID- 16591750
TI  - An example in surface area.
AB  - For length and area, a central fact is that the value of the length of a curve or
      the area of a surface, as given by the Lebesgue theory, is at least as great as
      that given by the classical formula, whenever the latter has meaning. This is now
      found not to be valid in higher dimensions. We give an example of a continuous
      mapping of the unit cube into itself for which the value given by the formula
      exceeds the three-dimensional Lebesgue area of the corresponding suface.

PMID- 16591751
TI  - Flexible power-associative algebras of degree 1.
AB  - It is shown here that there are essentially two different types of simple
      flexible, strictly power-associative finite dimensional algebras of degree 1;
      namely, the fields and the algebras of Kokoris. This follows readily from the
      perhaps more basic result that characterizes the simple commutative power
      associative finite dimensional algebras of degree 1 as fields.

PMID- 16591752
TI  - THE EFFECT OF REDOX POTENTIAL ON P870 FLUORESCENCE IN REACTION CENTERS FROM
      Rhodopseudomonas spheroides.
AB  - We have prepared photosynthetic reaction centers from Rhodopseudomonas spheroides
      and have studied the fluorescence of the photochemical electron donor, P870. The
      yield of this fluorescence rises at low redox potential, presumably because the
      photochemical electron acceptor becomes reduced and the photochemical utilization
      of excitation energy is then prevented. The redox titration curve for this
      increase in the fluorescence has a shape corresponding to the transfer of one
      electron. The midpoint potential is -0.05 volt, independent of the pH from 6.5 to
      8.8. The amplitude of a light-induced absorbance change at 280 nanometers varies
      with redox potential and shows, at pH 7.5, a midpoint potential of 0.00 volt.
      These studies indicate that the primary photochemical electron acceptor is not
      ubiquinone and is not the substance responsible for the absorbance change at 280
      nanometers.

PMID- 16591753
TI  - Minimization of polypeptide energy, vi. Systematic searches for low-energy
      conformations of deca-L-alanine and the octapeptide loop of ribonuclease.
AB  - A succession of apparent local energy minima, in which the energies decrease
      successively, have been located for deca-L-alanine and the octapeptide loop of
      ribonuclease. The lowest energy minima were approximately 40 kcal/mole lower than
      the highest ones. The results suggest that the computational methods used here
      might be of considerable use in searching for the global energy minimum of larger
      polypeptides.

PMID- 16591754
TI  - On the decomposition of stress and strain tensors into spherical and deviatoric
      parts.
AB  - It is well known that Hooke's law for a linearly elastic, isotropic solid may be
      written in the form of two relations that involve only the spherical or only the
      deviatoric parts of the tensors of stress and strain. The example of the linearly
      elastic, transversely isotropic solid is used to show that this decomposition is
      not, in general, feasible for linearly elastic, anisotropic solids. The
      discussion is extended to a large class of work-hardening rigid, plastic solids,
      and it is shown that the considered decomposition can only be achieved for the
      incompressible solids of this class.

PMID- 16591755
TI  - Representations of weak and strong integrals in banach spaces.
AB  - We establish a representation of the Gelfand-Pettis (weak) integral in terms of
      unconditionally convergent series. Moreover, absolute convergence of the series
      is a necessary and sufficient condition in order that the weak integral coincide
      with the Bochner integral. Two applications of the representation are given. The
      first is a simplified proof of the countable additivity and absolute continuity
      of the indefinite weak integral. The second application is to probability theory;
      we characterize the conditional expectation of a weakly integrable function.

PMID- 16591756
TI  - Inward motions in connected spaces.
AB  - The concept of an A-set(1) is broadened and developed in an arbitrary connected
      T(1)-space X. Movements of such sets under arbitrary functions and under mildly
      restricted functions from X to itself are analyzed. Areas of constricted action
      are located which are imposed on the function by the structure of the space.
      Applications are made to the case where X is a dendrite. In this case existence
      of points of restricted motion is proved for arbitrary functions which yield
      actual fixed points in case of partly continuous functions.

PMID- 16591757
TI  - Toward a stochastic calculus, I.
AB  - Differential equations, deduced by physical theory for systems subjected to
      practically possible (Lipschitzian) random disturbances, can also be solved for
      martingale (e.g., Brownian-motion) disturbances by interpreting integrals as Ito
      integrals. But the two theories are not unified, and disconcerting differences
      appear. In this note and the next, we present the foundations of a unified
      theory, developed far enough to eliminate the discrepancies. Here we develop the
      tools; stochastic integration is extended to apply to a class of random functions
      including Lipschitzian and Brownian-motion processes, and a new kind of integral,
      called "doubly stochastic," is defined and shown to exist under adequately
      general hypotheses.

PMID- 16591758
TI  - Singular integrals and the principal series.
AB  - The L(2) theory of singular integral operators on nilpotent Lie groups is
      studied, extending known results for IR(n). The intertwining operators for the
      representations of the simple Lie groups of real rank one turn out to be of this
      type. As a result we determine which representations of the principal series of
      these groups are irreducible.

PMID- 16591759
TI  - Remarks on sequential point estimation.
AB  - We consider utilizing a sequential experiment for estimating the mean of a normal
      distribution when the variance of the distribution is unknown. For a suitable
      choice of the design constants of the experiment and for loss structures of
      practical interest, it is shown that the difference in the expected loss with
      optional stopping and the expected loss which would be incurred if sigma were
      known is a bounded function of sigma.

PMID- 16591760
TI  - On the law of the iterated logarithm.
AB  - The law of the iterated logarithm provides a family of bounds all of the same
      order such that with probability one only finitely many partial sums of a
      sequence of independent and identically distributed random variables exceed some
      members of the family, while for others infinitely many do so. In the former
      case, the total number of such excesses has therefore a proper probability
      distribution, and it is shown here that whenever the law applies this
      distribution possesses no moments of positive order. This result further
      elucidates the celebrated precision of this law of probability concerning
      fluctuations of sums of random variables.

PMID- 16591761
TI  - On the behavior of a capillary surface in a wedge.
AB  - Estimates above and below are obtained for the height of the equilibrium-free
      surface of a liquid when the liquid partially fills a cylindrical container whose
      cross section contains a corner with interior angle 2alpha. The surface is
      characterized by the condition that its mean curvature be proportional to its
      height above a reference plane (or, in the case of zero gravity, that the mean
      curvature be constant), and by the requirement that it meet the container wall
      with prescribed contact angle gamma. It turns out that the qualitative behavior
      of such a surface near the vertex changes markedly, according as alpha + gamma <
      (1/2)pi, or alpha + gamma >/= (1/2)pi. In the former case, the surface is either
      unbounded or fails to exist, while in the latter case every such surface is
      bounded. Some experimental comparisons are indicated, and an application to the
      problem of describing the mechanism of water rise in trees is discussed.The above
      results describe a limiting case among corresponding properties that hold for
      surfaces defined over domains with smooth boundaries. This extension is
      indicated, as well as a formal extension to n-dimensional surfaces; here the
      interest centers on the fact that it is the mean curvature of an (n-1)
      dimensional boundary element that controls the local behavior of the n
      dimensional solution surface.

PMID- 16591762
TI  - CULTURE OF CALLUS OF Hedera canariensis, WILLD.
AB  - Callus from stems of adult Hedera canariensis has been maintained on synthetic
      media for 29 successive passages over a period of three years. Callus from
      petioles of adult H. canariensis and from cotyledons has also been grown in
      culture.

PMID- 16591763
TI  - High efficiency, heterosis, and homeostasis in mitochondria of wheat.
AB  - Mitochondria of a wheat hybrid 31MS x 28 when assayed polarographically exceeded
      mitochondria of parents of the hybrid in ADP:O ratios and in respiratory control
      when they utilized alpha-ketoglutarate, malate, and succinate. The ADP:O ratios
      of the hybrid mitochondria for the three substrates were 5.8 +/- 0.2, 3.8 +/-
      0.15, and 3.4 +/- 0.2, respectively. High P:O ratios were also observed in
      manometric assays. Mixtures of parental mitochondria exceeded averages of the
      parents, i.e., they exhibited complementation and approached activities of hybrid
      mitochondria. Complementation was observed only with NAD-linked substrates.
      Dinitrophenol uncoupled all mitochondria, but uncoupling was smallest in hybrid
      mitochondria. Hybrid mitochondria had the greatest ATPase activity. Mixtures
      exhibited complementation in ATPase activity. ATPase activity was stimulated
      least in hybrid mitochondria and in parental mixtures. The results were discussed
      from the point of view that the high P:) ratios gave us direct evidence that
      heterosis is indeed characterized by high efficiency. It is also pointed out that
      because of consistent repeatability and their specificity to hybrids, P:O ratios
      studied in rapidly isolated mitochondria of hybrids may give us revealing
      information on supramaximal efficiency of oxidative phosphorylation.

PMID- 16591764
TI  - LOCALIZATION AND SECRETION OF SALT BY THE SALT GLANDS OF Tamarix aphylla.
AB  - Analysis of salt secreted by the salt glands of Tamarix aphylla shows that the
      composition of the secreted salt is dependent on the salt composition of the root
      environment. Rubidium ion, if added to culture solutions in which the plants were
      growing, is also taken up by the plants and subsequently secreted by the glands.
      Electron micrographs of glands from the ribidium-secreting plants show
      accumulations of electron-dense material in the microvacuoles of the secretory
      cells. It is concluded that rubidium is accumulated in the microvacuoles and
      subsequently secreted by their fusion with the plasmalemma.

PMID- 16591765
TI  - Computer-assisted learning: introduction and general considerations.

PMID- 16591766
TI  - The psychological heuristics of learning.

PMID- 16591767
TI  - Computer-assisted learning in action.

PMID- 16591768
TI  - Computers and the schools in modern society.

PMID- 16591769
TI  - Geometric programming, chemical equilibrium, and the anti-entropy function.
AB  - THE CULMINATION OF THIS PAPER IS THE FOLLOWING DUALITY PRINCIPLE OF
      THERMODYNAMICS: maximum S = minimum S(*). (1) The left side of relation (1) is
      the classical characterization of equilibrium. It says to maximize the entropy
      function S with respect to extensive variables which are subject to certain
      constraints. The right side of (1) is a new characterization of equilibrium and
      concerns minimization of an anti-entropy function S(*) with respect to intensive
      variables. Relation (1) is applied to the chemical equilibrium of a mixture of
      gases at constant temperature and volume. Then (1) specializes to minimum F =
      maximum F(*), (2) where F is the Helmholtz function for free energy and F(*) is
      an anti-Helmholtz function. The right-side of (2) is an unconstrained
      maximization problem and gives a simplified practical procedure for calculating
      equilibrium concentrations. We also give a direct proof of (2) by the duality
      theorem of geometric programming. The duality theorem of geometric programming
      states that minimum cost = maximum anti-cost. (30).

PMID- 16591770
TI  - On the fluctuations of sums of independent random variables.
AB  - If X(1), X(2),... are independent random variables with zero expectation and
      finite variances, the cumulative sums S(n) are, on the average, of the order of
      magnitude S(n), where S(n) (2) = E(S(n) (2)). The occasional maxima of the ratios
      S(n)/S(n) are surprisingly large and the problem is to estimate the extent of
      their probable fluctuations.Specifically, let S(n) (*) = (S(n) - b(n))/a(n),
      where {a(n)} and {b(n)}, two numerical sequences. For any interval I, denote by
      p(I) the probability that the event S(n) (*) epsilon I occurs for infinitely many
      n. Under mild conditions on {a(n)} and {b(n)}, it is shown that p(I) equals 0 or
      1 according as a certain series converges or diverges. To obtain the upper limit
      of S(n)/a(n), one has to set b(n) = +/- epsilon a(n), but finer results are
      obtained with smaller b(n). No assumptions concerning the under-lying
      distributions are made; the criteria explain structurally which features of
      {X(n)} affect the fluctuations, but for concrete results something about
      P{S(n)>a(n)} must be known. For example, a complete solution is possible when the
      X(n) are normal, replacing the classical law of the iterated logarithm. Further
      concrete estimates may be obtained by combining the new criteria with some
      recently developed limit theorems.

PMID- 16591771
TI  - Minimal immersions of spheres into spheres.
AB  - In this paper we announce a qualitative description of an important class of
      closed n-dimensional submanifolds of the m-dimensional sphere, namely, those
      which locally minimize the n-area in the same way that geodesics minimize the arc
      length and are themselves locally n-spheres of constant radius r; those r that
      may appear are called admissible. It is known that for n = 2 each admissible r
      determines a unique element of the above class. The main result here is that for
      each n >/= 3 and each admissible r >/= [unk]8 there exists a continuum of
      distinct such submanifolds.

PMID- 16591772
TI  - Applications of the radon transform to representations of semisimple lie groups.
AB  - From the point of view of the duality between points and horocycles in a
      symmetric space, the counterparts to the spherical functions on the symmetric
      space are the conical distributions on the manifold of horocycles. While the
      conical functions are closely related to certain finite-dimensional
      representations of semisimple Lie groups, in the present work the conical
      distributions are found to play various roles in the principal series of
      infinitedimensional representations of these groups.

PMID- 16591773
TI  - Direct solution of general one-dimensional linear parabolic equation via an
      abstract plancherel formula.
AB  - We use the formalism of Fourier transformation to derive a functional calculus
      for the generator of an abstract group. As an application we obtain a new direct
      solution of Cauchy's problem for one-dimensional stationary parabolic equations
      of arbitrary order with bounded coefficients.

PMID- 16591774
TI  - Cohomology of kleinian groups.
AB  - Let [unk] be a (nonelementary) Kleinian group and q >/= 2 an integer. The group
      [unk] acts in a natural way on the vector space II(2q-2) of complex polynomials
      in one variable of degree </= 2q - 2. One can thus form H(1)([unk],II(2q-2)), the
      first cohomology group of [unk] with coefficients in II(2q-2). There are
      essentially two ways of constructing cohomology classes. One construction
      originated with Eichler and has recently been extended by Ahlfors. Another
      construction is due to Bers. We show that for finitely generated [unk], every
      cohomology class pepsilon H(1)([unk],II(2q-2)) can be written uniquely (if one
      chooses an invariant union of components of [unk]) as a sum of a Bers cohomology
      class and an Eichler cohomology class. Similar decompositions are obtained for
      the subgroups of parabolic cohomology classes introduced by Ahlfors. Some
      information on the structure of H(1)([unk],II(2q-2)) for infinitely generated
      groups [unk] is also obtained.

PMID- 16591775
TI  - The plancherel formula for sl(2) over a local field.
AB  - More than two decades ago, in his classical paper on the irreducible unitary
      representations of the Lorentz group, V. Bargmann initiated the concrete study of
      Fourier analysis on real Lie groups and obtained the analogue of the classical
      Fourier expansion theorem in the case of the Lorentz group. Since then the
      general theory for real semisimple Lie groups has been extensively developed,
      chiefly through the work of Harish-Chandra. More generally, one may consider
      groups defined by algebraic equations over locally compact fields, in particular
      local fields, and ask for an explicit Fourier expansion formula. In the present
      article the authors obtain this formula for the group SL(2).

PMID- 16591776
TI  - Photorespiratory-induced senescence of plants under conditions of low carbon
      dioxide.
AB  - A light-induced senescence of soybeans at low carbon dioxide concentration has
      been characterized and ascribed to photorespiration. It is suggested that this
      system can be used to screen large numbers of plants for photorespiratory
      deficient individuals of photorespiratory species. Optimal conditions for this
      senescence include a low CO(2) concentration, a temperature near 34 degrees ,
      high light intensity, and a high oxygen concentration.

PMID- 16591777
TI  - ADAPTIVE SIGNIFICANCE OF PIGMENT POLYMORPHISMS IN COLIAS BUTTERFLIES, II.
      THERMOREGULATION AND PHOTOPERIODICALLY CONTROLLED MELANIN VARIATION IN Colias
      eurytheme.
AB  - The butterfly Colias eurytheme requires body temperatures above 30 degrees C for
      flight. When cold, it orients its exposed wing undersides to present maximum
      surface area to sunlight; when too warm, it orients for minimum exposure. Dark
      winged color forms heat faster in sunlight than light ones. The seasonal color
      polymorphism of Colias appears to have been evolved to maximize solar heating in
      cold seasons and minimize overheating in warm seasons.

PMID- 16591778
TI  - Partially purified photosynthetic reaction centers from plant tissues.
AB  - The prior removal of carotenoids from photosynthetic membranes of plants by means
      of organic extraction allows Triton X-100 to remove and solubilize small
      particles that are greatly enriched in reaction center Chl, P700. Four plant
      species have been examined: spinach, bush bean (Phaseolus vulgaris), the blue
      green alga Anabaena variabilis, and Euglena. The particles obtained are generally
      similar and have a ratio of one P700 to approximately 30 chlorophylls (in spinach
      the ratio is 1 to 28). Exposure of such particles to light or to ferrycyanide
      causes absorbance changes that are maximal in the vicinity of 700 and 680 nm. The
      former represents a bleaching (oxidation) of P700, and the latter appears to be
      caused by a red shift of some Chl closely associated with P700 in the reaction
      center. The kinetics of P700 oxidation and the fluorescent properties of such
      preparations indicate a decreased efficiency of energy transfer to the reaction
      center from the bulk Chl found on the particle.

PMID- 16591779
TI  - LIGHT-INDUCED OXIDATION OF A CHLOROPLAST B-TYPE CYTOCHROME AT -189 degrees C.
AB  - The b-type cytochromes of chloroplasts have heretofore been viewed as
      photosynthetic electron carriers that probably occupy an intermediate position in
      a light-induced electron flow. The oxidation-reduction of such intermediate
      electron carriers, being removed from the primary photochemical reaction linked
      to photon capture by chlorophyll, would be expected to show a temperature
      dependence. Evidence has now been obtained that cytochrome b(559) is
      photooxidized at -189 degrees C and that this photooxidation can be induced only
      by "short-wavelength" monochromatic light which activates the oxygen-evolving
      system in chloroplasts (photosystem II). In appears, therefore, that
      photooxidation of cytochrome b(559) is closely linked with photon capture by the
      chlorophyll pigments characteristic of photosystem II.

PMID- 16591780
TI  - Spectral evidence for a new photoreactive component of the oxygen-evolving system
      in photosynthesis.
AB  - On illuminating chloroplasts with "short-wavelength" monochromatic light that
      supports oxygen evolution, spectral evidence was obtained for a new photoreactive
      chloroplast component, provisionally designated C550, which shows a reversible
      decrease of absorbance with a maximum at 550 mmu. The light-induced absorbance
      changes in C550 have been separated from those due to cytochromes in the same
      spectral region.The light-induced decrease of absorbance in C550 appears to be
      independent of temperature, persisting even at -189 degrees and is therefore
      likely to be linked to the primary light reaction associated with oxygen
      evolution in photosynthesis.

PMID- 16591781
TI  - National academy of sciences: officers, council, and members.

PMID- 16591782
TI  - The relation between peroxidase activity and the morphological expression of the
      hooded gene in barley.
AB  - Reproductive meristems of the hooded (KK) genotype of barley at the stage of
      young lemma primordia were injected with the inhibitors sodium azide, hydrazine,
      and hydroxylamine at concentrations of 10(-3), 10(-4), and 10(-5)M, as well as
      with phenylboric acid. These treatments all brought about an altered expression
      of the adult phenotype in the direction of awned (kk) genotype. Analysis of
      tissues treated with the same reagents revealed a reduction in peroxidase
      activity which was proportional to the effect of each inhibitor in modifying the
      phenotypic expression of the gene. Exogenous IAA injected in the same manner
      brought about a similar modification of the phenotype and parallel reduction of
      peroxidase activity, but to a lesser degree. These results are believed to be
      caused by modifications of the action of the IAA oxidase system in the developing
      meristems.

PMID- 16591783
TI  - Avifaunal equilibria and species turnover rates on the channel islands of
      california.
AB  - Insular species diversities, and their dependence on island size and isolation,
      have been postulated to represent a dynamic equilibrium between species
      immigration rates and species extinction rates. This interpretation has been
      tested by determining the land and freshwater birds breeding on the nine Channel
      Islands off southern California in 1968 and comparing the results with a similar
      survey for the years up to 1917. Most of the islands were found to be in
      equilibrium as to number of species, but between 17 and 62 per cent of the 1917
      breeding species had disappeared by 1968, and an approximately equal number of
      new immigrant species had become established. Percentage turnover rates vary
      inversely as insular species diversities, with no effect of distance apparent.

PMID- 16591784
TI  - The origin of the nucleic Acid bases found in the royal jelly of the honeybee.
AB  - The discovery that the royal jelly of the honeybee contains large quantities of
      nucleic acids raises the question, "Where do these nucleic acids come from?" A
      review of pertinent literature strongly suggests that the same mechanism is
      involved as in the case of the extrachromosomal DNA of amphibian oocytes.

PMID- 16591785
TI  - An improved iteration method for the calculation of surface tension using the
      significant structure theory of liquids.
AB  - An improved iteration method for calculating the surface tension developed by
      Chang et al. is presented. To test it, the surface tensions of the following
      liquids are calculated: A, N(2), CH(4), PH(2), Br(2), C(6)H(6), HgCl(2), and
      TiCl(4).The calculated results show the present method is an improvement over
      that of Chang et al. In addition to the change in the energy of sublimation of a
      molecule in a surface layer, which Chang et al. considered, the less important
      but not negligible effects on the number of nearest neighbors, eta(i), and the
      characteristic temperature, theta(i), are now included. eta(i) is proportional to
      the effective local density, and theta(i) is proportional to the square root of
      the effective local density. The calculated values fit the experimental data
      somewhat more closely than those calculated by the original method of Chang et
      al.

PMID- 16591786
TI  - Ferromagnetism and superconductivity in uranium compounds.
AB  - The intimate correlation between the mechanisms causing magnetism and
      superconductivity in uranium compounds has been verified again-in novel systems.

PMID- 16591787
TI  - Some bilinear generating functions.
AB  - In the present paper, the author applies some of his earlier results which extend
      the well-known Hille-Hardy formula for the Laguerre polynomials to certain
      classes of generalized hypergeometric polynomials in order to derive various
      generalizations of a bilinear generating function for the Jacobi polynomials
      proved recently by Carlitz. The corresponding results for the polynomials of
      Legendre, Gegenbauer (or ultraspherical), Laguerre, etc., can be obtained fairly
      easily as the specialized or limiting cases of the generating functions presented
      here. It is also shown how the formula of Carlitz follows rather rapidly from a
      result of Weisner involving the Gaussian hypergeometric functions.

PMID- 16591788
TI  - Classification of the real infinite simple and real infinite primitive lie
      algebras.
AB  - In this paper the real infinite simple and real infinite primitive Lie algebras
      are classified.

PMID- 16591789
TI  - On the vitali-hahn-saks and nikodym theorems.
AB  - We present simplified proofs of the well-known Vitali-Hahn-Saks and Nikodym
      theorems for measures.

PMID- 16591790
TI  - Temperature and manganese as determining factors in the presence of diatom or
      blue-green algal floras in streams.
AB  - Diatoms are usually the major component of the algal flora in many streams,
      although green and blue-green algae may be present. These experiments were
      designed to determine if high temperature or a shift in the chemical composition
      of the water might bring about a dominance of blue-green algae and/or green algae
      rather than a dominance of diatoms in the algal flora.The results of these
      experiments indicate that an average temperature of 34 degrees to 38 degrees C
      results in a shift of dominance in the algal flora from diatoms to blue-green
      algae. Furthermore, a blue-green and green algal flora of species typically found
      in organically polluted water in favored if the manganese content is a few parts
      per billion. If the manganese content averaged 0.02-0.043 mg/liter in the natural
      stream to 0.04-0.28 mg/liter in the recycled water experiment, a diatom flora
      remained dominant.

PMID- 16591791
TI  - The high-energy light action controlling plant responses and development.
AB  - Evidence is advanced for a network of three photoreactions and five dark
      reactions in control of plant growth and development by phytochrome.

PMID- 16591792
TI  - QUANTITATIVE STUDY OF CLINAL VARIATION IN Juniperus virginiana USING TERPENOID
      DATA.
AB  - Nine populations of Juniperus virginiana were sampled at approximately 150-mile
      intervals along a 1500-mile transect from northeastern Texas to Washington, D.C.
      Individual plants were examined for terpenoids by gas liquid chromatography and
      the resulting data analyzed by numerical classification methods using characters
      weighted according to their estimated variance in the natural populations.The
      results of the analysis show that these populations of J. virginiana cluster
      clinally from northeast to southwest, the more homogeneous populations occurring
      in the Appalachian region of North America; the more divergent populations found
      in progressively more distant regions, as measured along the transect from the
      northeast toward the southwest. No biochemical evidence could be found to support
      the hypothesis that hybridization with J. ashei might be causing this
      variability, as had been widely supposed previously.

PMID- 16591793
TI  - AUXIN AND GROWTH OF EXCISED ROOTS OF Bryophyllum calycinum.
AB  - Exogenous auxin (alpha-naphthalene acetic acid, indole acetic acid, or 2,4
      dichlorophenoxyacetic acid) was essential for the growth of single excised root
      tips of Bryophyllum calycinum in 50 ml of a mineral salt-sucrose medium
      supplemented with vitamins. Large inocula with a dry weight of 2.0 mg or more
      grew with no auxin added to the medium. Evidence for the synthesis of auxin by
      the excised roots grown from the larger inocula is presented. Leaching of auxin
      from single root tips cultivated in 15 or 50 ml of basal medium is considered to
      account for their failure to grow.

PMID- 16591794
TI  - Correlated effects of ecdysone and neurosecretion in puparium formation
      (pupariation) of flies.
AB  - A neurohormone accelerates the formation and tanning of the fly puparium in the
      presence of ecdysone. When larvae of Phormia regina are divided by ligation into
      two parts before the critical period, the hind part remains untanned, unless
      injected with blood from a pupariating larva. This confirms earlier observations
      and is in contrast to recent data with another genus. When Sarcophaga bullata
      larvae are ligated after the critical period, the anterior part starts to tan
      about two hours before the posterior part. Injecting neurosecretory material from
      the brain, the pars intercerebralis, or the corpora cardiaca of S. bullata, or
      from the brain or c. cardiaca of Periplaneta or Pyrrhocoris into the posterior
      part induces it to tan before the anterior part. Injection of the same material
      into normal larvae after the critical period similarly accelerates puparium
      formation and onset of tanning. Injection of ecdysone or ecdysterone does not
      have these effects. Thus, the neurosecretory material does not act by causing the
      release of ecdysone from the ring gland and its function is different from that
      of the classical brain ("activating") hormone. When injected before the critical
      period together with ecdysone it potentiates the effect of ecdysone. It is
      suggested that its biological significance is to coordinate puparial contraction
      and tanning.

PMID- 16591795
TI  - ISOLATION OF beta-GLUCAN SYNTHETASE PARTICLES FROM PLANT CELLS AND IDENTIFICATION
      WITH GOLGI MEMBRANES.
AB  - A variety of particle-bound synthetases that use sugar nucleotides as glycosyl
      donors for the formation of polysaccharides similar to those of the cell wall
      have been demonstrated in mung beans and other plant tissues,(1) but the
      particles in question have not been previously identified.(2, 3) The
      polysaccharide synthetase particles from peas that form mainly beta-1,4-glucan
      from UDPG and GDPG have now been separated from other cell particles by
      combinations of velocity and isopycnic density gradient centrifugation. The
      particles have an effective density of about 1.15 gm cm(-3), exhibit latent
      nucleoside diphosphatase activity upon IDP, UDP, GDP, and to a lesser extent upon
      ADP, and also possess acid phosphatase and weak ATPase activity. The isolated
      synthetase particles consist of somewhat condensed Golgi dictyosomes and free
      dictyosomal membranes bearing vesicles. It is concluded that the synthetase
      particles are Golgi membranes. The nucleoside diphosphatase activity of these
      particles may represent inactivated polysaccharide synthetase.

PMID- 16591796
TI  - A concept of three light reactions in photosynthesis by green plants.
AB  - It has generally been accepted that plant photosynthesis involves two light
      reactions, one that proceeds best in short-wavelength light and is identified
      with oxygen evolution (System II) and another that proceeds best in long
      wavelength light and is identified with a cycle electron flow (System I). This
      paper presents a concept of three light reactions in photosynthesis, based on new
      evidence that System II comprises two rather than one short-wavelength light
      reaction. These appear to operate in series and to be connected by an electron
      transport chain peculiar to System II. Parallel to System II is the long
      wavelength light reaction of System I.

PMID- 16591797
TI  - Comparison of lunar with terrestrial and meteoritic rocks.
AB  - This note examines critically recent attempts to identify or closely correlate
      lunar surface samples-on the basis of alpha-scattering analysis-with terrestrial
      igneous rocks (basalts) or with eucrite meteorites. Basalts show considerable
      variety; but all have chemical characteristics inherited from terrestrial mantle
      rock melted under a limited range of terrestrial pressure-temperature conditions.
      What is characteristic is not so much the content of any particular element or
      oxide-e.g., SiO(2) 47-52 per cent-but rather a complete chemical pattern in which
      such ratios as Fe/Mg and Ca/(Na + K) show consistent relationships to Si content.
      These are the chemical criteria that might be useful in comparing terrestrial
      basalt with extraterrestrial rocks. Basalts also have distinctive mineralogical
      and textural characteristics; and if a lunar or meteoritic rock is to be
      identified as basalt it must possess these, too.Turkevich's analysis of alpha
      scattering data for lunar samples (Surveyor V) show significant departure from
      basaltic composition: Very high (Ca + K)/Na associated with distinctly high
      Fe/Mg. In basalts relatively high (Ca + K)/Na-in no case approaching the reported
      lunar values-tends to be associated with Fe/Mg values lower than average. The
      same "lunar" pattern of high (Ca + K)/Na and Fe/Mg appears in recorded analyses
      of eucrite meteorites. In the lunar samples, Ti is notably higher than in
      basalts, and even more so than in eucrites. If eucrites are of lunar origin their
      Ti values are, so far, a real anomaly.

PMID- 16591798
TI  - The unextractable organic fraction of the pueblito de allende meteorite: evidence
      for its indigenous nature.
AB  - The Pueblito de Allende meteorite contains only 0.1-0.5 ppm of solvent
      extractable carbon, most or all of which is due to terrestrial contamination.
      Determinations of the total carbon content gives values from 0.23 to 0.35 per
      cent. The presumed indigenous insoluble carbon is thus present in a ratio of
      2300:1 relative to contaminant carbon. A sample of the meteorite was extracted
      with a deuterated solvent containing benzene:methanol (4:1 w/w) to remove
      contaminants and then was subjected to pyrolysis-gas chromatography-mass
      spectrometry to investigate the nature of the remaining carbon. The pyrolysis
      products (about 20 ppm) consisted chiefly of aromatic and substituted aromatic
      hydrocarbons. The pyrolysis results were confirmed by oxidative thermal analysis
      which showed that the bulk of the carbon present was a macromolecular structure
      and not graphite. This suggests that an insoluble nongraphitic condensed aromatic
      polymer is indigenous to the meteorite. The origin and precise chemical structure
      of this material has not been determined, but it bears a superficial resemblance
      to coal-like structures.

PMID- 16591799
TI  - Orbiting clusters in atomic nuclei.
AB  - As an alternative to their description as vibrational levels, the low excited
      states of even-even nuclei can be described as rotational states of a helion,
      dineutron, diproton, or other cluster about the rest of the nucleus, leading to
      reasonable values of the average distance between centers of the clusters. Some
      states involve rotational excitation of two or more helions or other clusters.
      The nature of the rotating clusters is determined by the relation of the neutron
      and proton numbers to the magic numbers.

PMID- 16591800
TI  - Wind directions aloft and effects of seeding on precipitation in the whitetop
      experiment.
AB  - The subdivision of all the experimental days of the Whitetop project into two
      approximately equal groups, group W with predominantly westerly winds aloft and
      group E with frequent easterly winds, shows a remarkable difference in the
      apparent effect of seeding. On W days there was no detectable effect of seeding
      on rainfall. On E days with seeding, the average 24 hour precipitation in an area
      of about 100,000 square miles was significantly less than that without seeding by
      46 per cent of the latter. The decrease resulted from a "decapitation" of the
      usual afternoon rise in rainfall. It may be significant that the afternoon
      maximum of natural precipitation on E days occurs some two hours later than on W
      days. If the actual cause of the differences in rainfall was seeding, then the
      loss of water resulting from operational, rather than experimental, seeding would
      have averaged eight million acre-feet per summer.

PMID- 16591801
TI  - Algebraic characterization of polynomials whose zeros lie in certain algebraic
      domains.
AB  - A new algebraic criterion is given for a polynomial phi with complex coefficients
      to have all its zeros in a certain type of algebraic region T of the complex
      plane. In particular, T may be any circle or half plane. The criterion is
      effectively computable from the coefficients of the polynomial phi. The classical
      results of Hermite, Hurwitz, Lyapunov, Schur-Cohn, and others appear as special
      cases of the new criterion.

PMID- 16591802
TI  - Structure and optical activity in metal complexes, vi. Interaction of histidine
      with copper(ii) in solution.
AB  - The species existing in aqueous solution at pH 8.3 when copper(II) interacts with
      two equivalents of L-histidine has been studied by a variety of techniques. The
      evidence is consistent with a fluctuating type of coordination for the
      histidinato-copper(II) complex, which varies according to conditions and other
      coordinating ligands involved.

PMID- 16591803
TI  - Sedimentation equilibrium of polydisperse nonideal solutes: a comparison of three
      approximations.
AB  - In the evaluation of sedimentation equilibrium data for polydisperse nonideal
      solutions, extrapolation procedures are required for the determination of the
      true solute weight-average molecular weight and of the light-scattering second
      virial coefficient. In an attempt to decide just which concentration-dependent
      parameter should be used in making these extrapolations, Van Holde and Williams,
      J. Polym. Sci., 11, 243 (1953), and Fujita, J. Phys. Chem., 63, 1326 (1959), and
      ibid., 73, 1759(1969), have derived relations between apparent and true weight
      average molecular weights which, starting from approximate forms of the same
      differential equations, appear to give different working expressions. The present
      analysis of these results will demonstrate new and perhaps unexpected relations
      between them.Further, these approximations are discussed in terms of certain of
      the available experimental data, the purpose being to clarify the conditions
      under which the behavior of a polydisperse nonideal solution in the
      ultracentrifuge may be treated as if a nonideal two-component system were
      involved.

PMID- 16591804
TI  - Induction of fern spore germination.
AB  - Light-induced germination of Anemia spores can be inhibited by AMO-1618, a
      selective inhibitor of gibberellin biosynthesis. The inhibitor has no effect on
      gibberellin-induced dark germination and its inhibition of light-induced
      germination can be reversed by supplying gibberellin. Barley-endosperm bioassay
      of concentrates of medium in which spores are imbibed in light reveals the
      presence of substances with gibberellin-like activity; assay of medium from dark
      imbibed spores does not. Simultaneous exposure of spores to sub-optimal levels of
      light and gibberellin leads to additivity of effect on germination level. Uptake
      of labeled gibberellin by spores in light is similar to that in darkness. The
      implications of these findings for the light-dependent synthesis of a gibberellin
      like germination substance are discussed. The bearing of the observations upon
      understanding the interaction of light and gibberellins in seeds of higher plants
      is considered.

PMID- 16591805
TI  - Rare Earth impurities in yb(6) and zrb(12).
AB  - We present data on the depression of the superconducting transition temperatures
      of YB(6) and ZrB(12) by rare earth impurities. These data show unusual features.
      Ce in YB(6) is in some ways analogous to Yb in ZrB(12), and this analogy also
      appears to hold between Ce in CeB(6) and YB in YbB(12).

PMID- 16591806
TI  - Right-shift processes.
AB  - We present a class of Markov processes with multidimensional finite state space
      on which the infinitesimal transition movement is a shifting of one unit from one
      coordinate to some other to its right. We show how to represent the Kolmogorov
      forward equations as a triangular system.

PMID- 16591807
TI  - Studies of isozyme patterns in nullisomic-tetrasomic combinations of hexaploid
      wheat.
AB  - Thirty-eight wheat strains, each nullisomic for one chromosome and tetrasomic for
      a homoeologous (related) one, were analyzed electrophoretically for 12 different
      enzymes, and a gene (or genes) for alkaline phosphatase was localized to
      chromosomes 4B and 4D. The other 11 enzymes showed no significant electrophoretic
      variation. The fact that the only mutants observed affect the same enzyme favors
      the concept that rigorous selection operates in the polyploids both to preserve
      certain types of variants and to eliminate others.

PMID- 16591808
TI  - Relative diffusivities of methane in water and carbon tetrachloride.
AB  - Methane diffuses in water at 25 degrees C 3/5 as fast as it does in carbon
      tetrachloride. Since diffusivity depends mainly upon temperature, viscosity of
      the solvent, and molecular cross section of the diffusant, and since viscosities
      of H(2)O and CCl(4) at 25 degrees C are almost identical, one may infer that
      molecules of CH(4) in H(2)O are not imprisoned in "icebergs," and are retarded
      only by hydrogen bonds, not by encounters with "ice-like" aggregates.

PMID- 16591809
TI  - Thermodynamic parameters for dissolved gases.
AB  - In 1958 and subsequently we correlated properties of solutions of gases in
      liquids by using the "force constants," epsilon/k, and collision diameters,
      sigma, which serve as parameters in equations for molecular pair potential energy
      such as that of Lennard-Jones or its variants. Unfortunately, however, the
      figures for these parameters that have been published are so scattered for the
      same gas as to make it difficult to select "best" values; in 1967, therefore, I
      substituted for these indirectly determined molecular parameters the directly and
      accurately known molal energy of vaporization, DeltaE(b) (v), and the molal
      volume, v(b), of the liquefied gas, both at its boiling point. A plot of values
      of DeltaE(2) (v) against the most trustworthy values of epsilon/k reveals direct
      proportionality. The same is true for V(b) (1/3) versus sigma.Recent examples
      will be shown of excellent linear correlations with these parameters of
      thermodynamic properties of different gases in the same solvent.It is no less
      "scientific" and far more practical to regard molecules of a solute as immersed
      in the potential energy field of its solvent than it is to split this field into
      imperfectly known pair potentials of questionable additivity and to try to
      integrate them over an undetermined distribution function.

PMID- 16591810
TI  - Species packing, and what competition minimizes.
AB  - Species competing exclusively for renewing resources are shown to obey
      simultaneous differential equations equivalent to the conditions for minimizing a
      certain quadratic form. In this sense competition acts to select species
      abundances giving the best least-squares fit in an expression [Formula: see text]
      Thus the number of species which can coexist competitively is limited mostly by
      the inequality of the interspecies competition coefficients and not appreciably
      by their magnitude. Seasonality and number of resources become the main factors
      limiting the number of coexisting species.

PMID- 16591811
TI  - Scientific program and abstracts of contributed papers.

PMID- 16591812
TI  - Inference from inadequate and inaccurate data, I.
AB  - Having measured D numerical properties of a physical object E which requires many
      more than D parameters for its complete specification, an observer seeks to
      estimate P other numerical properties of E. This paper describes how he can
      proceed when E is adequately described by one member m(E) of a Hilbert space
      [unk] of possible models of E, when he believes that the Hilbert norm of m(E) is
      very likely rather smaller than some known number M, and (except for section 6)
      when all the observed and sought-after properties of E are continuous linear
      functionals on [unk]. Section 6 treats Frechet-differentiable non-linear
      functionals. A later paper will reduce unbounded functionals on arbitrary
      topological linear spaces to the present case.

PMID- 16591813
TI  - Noncommutative jordan algebras with commutators satisfying an alternativity
      condition.
AB  - The theorems of this paper show that the main results in the structure and
      representation theory of Jordan algebras and of alternative algebras are valid
      for a larger class of algebras defined by simple identities which obviously hold
      in the Jordan and alternative cass. A new unification of the Jordan and
      associative theories is also achieved.

PMID- 16591814
TI  - Fourier Analysis on GL(n,R).
AB  - Two problems of Fourier analysis on GL(n,R) are studied. The first concerns the
      decomposition of the additive Fourier operator in terms of the group
      representation theory of G. The second concerns the analytic continuation of
      certain zeta-functions defined on G. It is found that the generalized Gamma
      functions of Gelfand and Graev arise naturally in the solution of both these
      problems.

PMID- 16591815
TI  - A setting for a theorem of bott.
AB  - Inspired by Theorem A of Raoul Bott,(1) Morse and Cairns(2) have stated Corollary
      23.3 below, a theorem of essentially the same character as Theorem A of Bott. The
      symbol [unk] in Corollary 23.3 means that the sets to the left and right of [unk]
      have the same homotopy type in the sense of Hilton (ref. 3, p. 3). Corollary 23.3
      gives a setting to Bott's theorem in the theory of "bowls" introduced by Morse.
      The object of this note is to clarify and reinterpret the analysis presented as
      proof of Corollary 23.3 in reference 2.

PMID- 16591816
TI  - Biscalar and Bivector Green's Functions in de Sitter Space Time.
AB  - Biscalar and bivector Green's functions of wave equations are calculated
      explicitly in de Sitter space time. The calculation is performed by considering
      the electromagnetic field generated by the spontaneous creation of an electric
      charge.

PMID- 16591817
TI  - Higher dimensional mappings for which the area formula holds.
AB  - For each continuous mapping of 2 space into n space, n >/= 2, the Lebesgue area
      is given by the classical formula provided that the partial derivatives exist
      almost everywhere and belong to the class L(2). The analogous question for
      mappings of m space into n space, 2 < m </= n, has been open for a long time. We
      answer this question in the affirmative in a more general setting. Accordingly,
      as a special case, we show that if a continuous mapping of m space into n space,
      m </= n, has partial derivatives which belong to L(m) then the Lebesgue area is
      given by the classical formula.

PMID- 16591818
TI  - A differential equation for an eisenstein series of genus two.
AB  - A nonlinear differential equation of order 8 satisfied by the Eisenstein series
      of weight 4 for Siegel's modular group of genus two is presented. This equation
      plays a role in the theory of modular functions of genus two similar to that
      played by the differential equation of the Weierstrass [unk]-function associated
      with elliptic curve.

PMID- 16591819
TI  - Report on the teichmuller metric.
AB  - Let T(g) be the Teichmuller space of compact Riemann surfaces of genus g. Then
      T(g) is the space of conformal structures on a fixed surface W modulo equivalence
      under conformal maps homotopic to the identity. The Teichmuller modular group
      [unk] is the group of all orientation preserving homeomorphisms of W onto itself
      modulo those which are homotopic to the identity. Each element of [unk] induces a
      biholomorphic map of T(g) onto itself, and the present note outlines a proof of
      the converse statement: Every biholomorphic map of T(g) onto itself is induced by
      an element of [unk]. It is first shown that every isometry of T(g) with the
      Teichmuller metric arises from an element of [unk]. The Teichmuller metric is
      then shown to be the Kobayashi metric for T(g) and hence invariant under
      biholomorphic maps.

PMID- 16591820
TI  - Effect of rectangle length on velocity thresholds for real movement.
AB  - New data are reported on the influence of size on the velocity threshold for real
      movement. As the length of a narrow stimulus object increases, width remaining
      constant, the velocity threshold also increases. These findings are discussed in
      relation to some psychophysical experiments on contrast and some physiological
      experiments on motion.

PMID- 16591821
TI  - Control of nitrate reductase activity in barley aleurone layers.
AB  - Nitrate reductase activity in barley (Hordeum vulgare L. cv. Himalaya) aleurone
      layers has been determined in the intact tissue, using two different methods. The
      first method measures the rate of appearance of H(2) (18)O produced during the
      reduction of KN(18)O(3). The second assay measures excreted nitrite resulting
      from nitrate reduction under anaerobic conditions. Nitrite production in this
      anaerobic, intact-tissue assay was dependent upon the presence of phosphate (pH
      7.5) and was increased by ethanol and bisulfite.After ten hours of nitrate
      induction, nitrate reductase activities measured by the KN(18)O(3) assay are one
      sixth, and those measured by the anaerobic intact-tissue assay are one-third, of
      those observed in cell-free extracts of aleurone layers. Addition of ethanol to
      the anaerobic intact-tissue medium increased the rate of nitrate reduction to a
      level greater than that found in the cell-free assay.Oxygen inhibited nitrite
      release in the anaerobic intact-tissue assay. However, under aerobic conditions
      and in the presence of 2-heptyl-4-hydroxyquinoline-N-oxide or antimycin A,
      nitrate reduction increased to rates comparable to those observed under
      anaerobiosis. Neither of these electron transport inhibitors affected anaerobic
      nitrate reduction, though they were effective in inhibiting oxygen uptake in
      separate experiments.

PMID- 16591822
TI  - The [NeIV] Lines in High Excitation Gaseous Nebulae.
AB  - The "forbidden" lines of three times ionized neon are among the most precious
      indicators of electron temperature and excitation. They are also predicted to be
      among the strongest lines observed in the far ultraviolet spectra of high
      excitation nebulae.

PMID- 16591823
TI  - Dynamics of systems with large number of degrees of freedom and generalized
      transformation theory.
AB  - A generalized transformation theory which leads to a non-Hamiltonian description
      of dynamics is introduced. The transformation is such that all averages of
      observables remain invariant. However, the time evolution of the density matrix
      can no longer be expressed in terms of a commutator with the Hamiltonian.
      Therefore such transformations are not canonical in the usual sense. An explicit
      "two components" representation of the equations of motion is given which has the
      following properties: (a) each of the components satisfies a separate equation of
      motion, and (b) one component satisfies a kinetic equation of a generalized
      Boltzmann type.WE OBTAIN, THEREFORE, THE MOST REMARKABLE RESULT THAT THE RELATION
      BETWEEN DYNAMICS AND STATISTICAL MECHANICS (OR THERMODYNAMICS) TAKES A SPECIALLY
      TRANSPARENT AND SIMPLE FORM: thermodynamics appears in a precise sense as the
      random phase approximation of dynamics.Other problems such as the meaning of
      diagonalization of the Hamiltonian and definition of excitations will be treated
      in a forthcoming paper.

PMID- 16591824
TI  - The anomalous deuterium isotope effect on the chemical shift of the bridge
      hydrogen in the enol tautomer of 2,4-pentanedione.
AB  - The nature of the intramolecular hydrogen bond in the enol tautomer of 2,4
      pentanedione has been investigated by high resolution proton and deuteron
      magnetic resonance spectroscopy. An unusually large deuterium isotope effect on
      the chemical shift of the bridge hydrogen has been observed. This unexpected
      result, together with the observation of a pronounced temperature dependence for
      both the proton and deuteron resonances, suggests that two states with different
      chemical shifts for the bridge hydrogen are involved in rapid equilibrium and
      that the anomalous deuterium isotope effect has its origin in the effect of
      deuterium substitution on the energy separation between these states. It is
      proposed that these states correspond to the symmetrical and asymmetrical
      structures of the intramolecular hydrogen bond.

PMID- 16591825
TI  - Failure of Energy Transfer between Identical Aromatic Molecules on Excitation at
      the Long Wave Edge of the Absorption Spectrum.
AB  - Electronic energy transfer among identical molecules has been followed by the
      depolarization of the fluorescence in concentrated solutions as well as in
      dimers, polymers, and micelle systems. In the many aromatic fluorophores
      examined, unlike a few nonaromatic ones, transfer is much decreased or altogether
      undetectable on excitation at the red edge of the absorption spectrum. The
      phenomenon is not due to the transfer taking place during a small fraction of the
      total fluorescence lifetime, nor is it explainable by a decrease in overlap of
      absorption and emission upon edge excitation.

PMID- 16591826
TI  - Mixtures and characteristic functions.
AB  - Let g(u|c,y) = exp {ySigmac(k)(u(k) - 1)} with y > 0, Sigma(k=0) (infinity)c(k) =
      1,|u| < 1, and c standing for {c(k)}, be a probability generating function of a
      nonnegative integer-valued random variable. Let S be a distribution function on
      (0, infinity) non-degenerate at zero. The functions g and S determine another
      probability generating function, G(u|Sc) = integral(0) (infinity)gdS(y). One of
      the results obtained asserts that, if the sequence c is finite and the
      characteristic function of S is entire, then G determines uniquely both S and c.
      The assertion does not hold if these conditions are not satisfied. Another group
      of results refers to properties of characteristic functions. Let P(z) be a
      polynomial of degree m and f(z|y) = exp- {yP(z)}. The theorem of Marcinkiewicz
      asserts that with m > 2 the function f cannot be a characteristic function. It is
      shown that, if the characteristic function of S is entire, then F(z) =
      integral(0) (infinity)f(z|y)dS(y) can be characteristic function only if m </= 2.
      Again the assertion need not be true if the characteristic function of S is not
      entire.

PMID- 16591827
TI  - Simplifying intersections of surfaces.
AB  - Suppose mu and v are arcs whose union is an arc alpha and whose intersection is
      an arc beta. Suppose further that mu and v, respectively, lie in the boundaries
      of the disks M and N. It is shown that either alpha lies on the boundary of a
      disk or mu and v, respectively, lie in the boundaries of disks M' and N' which
      meet only in the arc beta. The construction is basic to recent results exploring
      new questions formerly considered only in the piecewise linear category.

PMID- 16591828
TI  - Light pulse propagation in nonlinear dispersive medium.
AB  - We investigate the evolution of an optical pulse in a dispersive, nonlinear
      dielectric material. The technique exploits two adiabatic invariants, action and
      wave number. The analysis is performed in detail for a nonlinear variant of the
      Lorentz model. We find that there are two nonlinear generalizations of the linear
      group velocity. From this we predict that optical shocks can form on either the
      front or back edge of the wave form.

PMID- 16591829
TI  - Interpretation of the [ClIII] Lines in Gaseous Nebulae.
AB  - The intensity ratio of the green lambdalambda5517 and 5537 lines of [ClIII]
      serves as an indicatrix of the electron density in many gaseous nebulae whose
      spectra can be observed with an image converter. Quantitative interpretation of
      the line ratio requires accurate values of the collisional strengths and
      transition probabilities. With improved values of these parameters we have
      revised electron densities for a number of nebulae; the results seem to be in
      good accord with those derived from other criteria.

PMID- 16591830
TI  - Singular Integrals and the Principal Series, II.
AB  - A further study is made of the intertwining operators for the representations of
      the simple Lie groups of real rank one. We extend and apply this to the higher
      rank case, obtaining various results dealing with reducibility of principal
      series and existence of complementary series.

PMID- 16591831
TI  - Cyclic Changes in Thylakoid Membranes of Synchronized Chlamydomonas reinhardi.
AB  - Cyclic variations in the activity of photosystems I and II occur during the cell
      cycle of wild-type Chlamydomonas reinhardi. These variations have been localized
      to chloroplast thylakoid membranes and correlated with corresponding changes in
      the ratio of chloroplast cytochromes to chlorophyll.

PMID- 16591832
TI  - Statistical theories of success.
AB  - The Pareto and the log-normal distributions are commonly used to describe the
      statistical distribution of success. A detailed comparison of these distributions
      is made with Lotka's extensive observations on success as measured by rate of
      publication. These distributions are found to adequately describe the observed
      distribution only for low and moderate success. Contrariwise, the flat factor
      analysis of performance recently developed by the author in these Proceedings
      (59, 1078 (1968)) is shown to give an excellent agreement over the whole range of
      success. Lotka's data allows a determination of the number of environmental
      factors.The Pareto distribution does give an excellent agreement with the tail of
      the success distribution where success is defined as income. An interpretation of
      this distribution is here presented based upon the expected behavior of
      entrepreneurs.

PMID- 16591833
TI  - Axonal growth from insect neurons in glia-free cultures.
AB  - Mechanical dissociation of nerve and glial cells from 16-day embryos of the
      cockroach Periplaneta americana and their subsequent culture in a Co(2)
      conditioned, chemically defined medium results in the survival of neurons but not
      of glial cells. The dissociated nerve cells remain alive and in excellent
      condition for many months and build a dense fibrillar network in presence of
      foregut explants from the same embryos. These explants are invaded by numerous
      and large fiber bundles emerging from the fibrillar network. The morphological
      characteristics of nerve cells and the structural and ultrastructural features of
      nerve bundles in long-term glia-free culture are described.

PMID- 16591834
TI  - Search for Positronium Lyman alpha-Radiation from Positrons Stopped in Inert
      Gases.
AB  - An attempt to detect the positronium Lyman alpha-radiation at 2430 A is reported.
      Positrons from an intense (64)Cu source (20 Ci) were stopped in high purity A,
      Ne, and He at pressures ranging from 0.01 to 3.0 atm. Light from the stopping
      region was collected by a large solid-angle light pipe and directed to a
      photomultiplier. Spectra were obtained by inserting a series of optical
      interference filters in front of the photomultiplier. Identical spectra were
      obtained with an intense electron emitter replacing the (64)Cu source. These
      results indicate that any Lyman alpha-radiation present at the photomultiplier is
      masked by a large background continuum associated with gas excitation processes.
      The data were employed to set an upper limit of 1 in 2000 on those positrons
      stopping in the gas which result in Lyman alpha-radiation.

PMID- 16591835
TI  - Premeiotic DNA Synthesis and the Time of Chromosome Pairing in Locusta
      migratoria.
AB  - Labeled spermatocytes from locusts killed 0, 1, 2, 3, 4, and 6 days after
      exposure to tritiated thymidine were examined with the electron microscope to
      determine their meiotic stage. It was found that tritiated thymidine uptake in
      young spermatocyte nuclei is completed some 24 hours before synaptinemal
      complexes are formed. It is concluded that in the locust, premeiotic DNA
      synthesis is completed well in advance of pairing of homologous chromosomes as
      marked by the formation of synaptinemal complexes. The G-1 and the S-phase are in
      the order of 24 hours each, while meiotic prophase lasts four to five days under
      the conditions used.

PMID- 16591836
TI  - Active Site of alpha-Chymotrypsin Activation by Association-Desolvation.
AB  - High reactivity toward alpha-chymotrypsin is observed for derivatives of beta
      arylpropionic acids of varied structure-L-alpha-acylamido compounds, D-cyclized
      compounds, and, now, L-glycolamide esters. Compensating enthalpy and entropy
      effects are observed which appear to be caused by changes in water of solvation.
      High reactivity with varied structure, and physical evidence, appear to rule out
      induced fit and distortion as important for this enzyme. The high reactivity
      results from precise fit of the hydrolyzing group at the critical serine
      imidazole junction, resulting from binding of the aryl group and restriction of
      rotation. Part of the energy of binding is used to desolvate the reactant groups
      of substrate and enzyme, decreasing activation energies by several kilocalories
      and raising reactivity by 10(3) or more. Solvation by water stabilizes many
      compounds, allowing them to be present in solution in biological systems. Their
      reactions may occur as their reactivity is increased when they are desolvated and
      brought from solution into association with reactive groups in enzymes,
      membranes, and structured particles.

PMID- 16591837
TI  - Is the breakdown of the born-oppenheimer approximation responsible for internal
      conversion in large molecules?
AB  - Vibronic radiationless transitions in large polyatomic molecules can be thought
      of as a process whereby the molecule, initially prepared in a discrete
      quasistationary state, makes a transition to an adjoining vibronic continuum
      belonging to a lower electronic state of the same multiplicity. In many instances
      the transition is analogous to penetration through a barrier between two "nested"
      potential sheets far away from an actual intersection of the sheets. Simultaneous
      distortions of vibrational and electronic parts of the wavefunction are required
      for such a tunneling process. The vibrational distortion manifests itself in the
      familiar Franck-Condon effect. The electronic distortion can be caused by
      nontotally symmetric vibrations of the molecule either because of the displaced
      nuclear configuration, to which the electrons instantly respond (Herzberg-Teller
      effect), or because of the protracted response of the electrons to the kinetic
      energy of nuclear motion (nonadiabatic effect or the breakdown of the Born
      Oppenheimer approximation). It is found here that Herzberg-Teller coupling is
      more effective in causing radiationless transitions than the breakdown of the
      Born-Oppenheimer approximation when the potential surfaces involved are not close
      to an intersection.

PMID- 16591838
TI  - Characteristic classes and weyl tensor: applications to general relativity.
AB  - In a recent paper, Chern and Simons proved that the Pontrjagin forms of a
      Riemannian manifold remain invariant under a conformal deformation. We show that
      these forms can be expressed uniquely in terms of the conformal curvature tensor:
      this provides a new proof of their result. Similar techniques can be applied to
      Euler-Poincare characteristic class, as suggested to me by A. Taub. We obtain the
      following: If the Weyl tensor of a compact space time is of type III of Bel
      Petrov, then it cannot carry a perfect fluid + electromagnetic field.

PMID- 16591839
TI  - A singular abstract cauchy problem.
AB  - In this note a singular abstract Cauchy problem is considered. A solution is
      obtained for this problem in terms of a regular abstract Cauchy problem. As an
      application we obtain a new solution of the initial value problem for a class of
      singular partial differential equations.

PMID- 16591840
TI  - Theory of a class of locally convex vector lattices which include the lebesgue
      spaces.
AB  - In this paper is presented the theory of a class of locally convex lattices (L
      lattices) of real functions which generalize the classical Lebesgue spaces. The
      monotone and dominated convergence theorems for convergence almost everywhere and
      sequential and order completeness of such lattices are established. These results
      are obtained through characterization of linear lattices of functions closed
      under pointwise or dominated convergence everywhere and closed under Stone's
      operation f --> f[unk]1. Such lattices are characterized in terms of
      measurability with respect to sigma or delta rings.Application to the theory of
      Lebesgue integrals is given, permitting one to obtain the classical theory of the
      integral and of the L(p) spaces directly from the axioms of the integral.
      Representations of L-lattices in terms of Lebesgue integrals and extensions of L
      lattices through addition of null functions are given.

PMID- 16591841
TI  - Excitation of Metastable Levels in Low Density Nebular Plasmas: [SII] and [ArIV].
AB  - Diagnostics of low density nebular plasma by means of its forbidden line spectrum
      require not only a knowledge of certain intensity ratios as a function of its
      density and temperature but also a knowledge of the occupation numbers of
      relevant ionic levels. We present the necessary data for important levels of
      ionized sulfur and triply ionized argon.

PMID- 16591842
TI  - Temporal phenotypic heterogeneity as a substrate for selection.
AB  - The interaction of temporal phenotypic heterogeneity with a population level
      fitness function was explored through the use of a simple model. The model, based
      upon experimental data, assumes that the exploitation of pollinators, and seed
      set within plant populations are dependent upon the frequency of a pink flower
      morph in populations composed of pink and white morphs. An increase in pink
      frequency is accompanied by an increase in seed-set for both morphs. The model
      also assumes that seed-set within a population is the same for pink and white
      individuals. In perennials and annuals with long-lived seeds, fluctuations in
      morph balance from one season to another may lead to reproductive pulses or
      drags, depending upon which morph was in excess. The reproductive differential
      which stems from different levels of pollinator service leads to an increase in
      pink frequency and an attendant fitness gain. The perennial habit and long-lived
      seeds provide a population with a memory which permits the current population
      image to compete with images of previous years. As a consequence, fitness gains
      may be achieved in the absence of interplant or interpopulation selection.

PMID- 16591843
TI  - A source for the special catalytic power of enzymes: orbital steering.
AB  - The velocities of acid catalyzed esterification and gamma-lactonizations were
      studied to test the sensitivity of a chemical reaction to the orientation of the
      reacting atoms. Variation in orientation of the attacking oxygen atom relative to
      the carbon atom of the carboxylic acid was achieved by using bicyclic ring
      systems to limit the conformational mobility of the gamma-hydroxy acids. Factors
      as high as 2 x 10(4) were observed for the acceleration of a reaction due to this
      "orientation factor" even after corrections for proximity and torsional strain
      have been made. The orientation factor is related to the shape of the electron
      orbitals and must have an angular preference far greater than previously
      estimated. Such sensitivity to orientation would provide factors large enough to
      explain the gap in our understanding of enzyme catalysis. It is suggested that
      the catalytic efficiency of enzymes depends on their ability not only to
      juxtapose the reacting atoms but also to "steer" their orbitals along a path
      which takes advantage of this strong directional preference.

PMID- 16591844
TI  - Theoretical investigations of automimicry, I. Single trial learning.
AB  - The theory of automimicry is explored mathematically on the assumption that
      predators can learn to avoid noxious prey by sight for some finite period after a
      single noxious experience. Automimetic advantage is an inevitable consequence of
      the evolution of an unpalatability dimorphism. An established automimetic
      situation is analogous to an established perfect Batesian mimicry situation,
      although the evolutionary bases of the two phenomena are different. In both
      situations, the mimetic advantage depends upon the proportion of unpalatable
      prey, the memory span of the predators, and the abundance of the prey relative to
      the predators. Automimetic advantage is maximal when the prey are neither too
      common nor too rare. Remarkably low proportions of unpalatable prey can confer
      very substantial immunity to the population. A surprising prediction of the model
      is that the evolution of unpalatability will not occur in rare prey species
      unless they first become Batesian mimics. This in turn could lead to the
      evolution of mimicry complexes containing many species forming a whole spectrum
      of unpalatability.

PMID- 16591845
TI  - Acetylene reduction assay for determination of phosphorus availability in
      wisconsin lakes.
AB  - Phosphorus-starved cells of Anabaena flos-aquae rapidly increase their capacity
      to reduce acetylene to ethylene when they receive phosphorus. This response may
      be used as a bioassay for detecting available phosphorus in aquatic ecosystems.
      The sensitivity of the method compares favorably with conventional methods for
      measuring dissolved orthophosphate, and has the additional advantage that it
      measures available phosphorus. Studies on Wisconsin lakes show that available
      phosphorus generally is present, that the concentrations are higher at the lower
      depths than at the surface, and that there may be diurnal variations in the
      available phosphorus content of surface waters. Important sources of available
      phosphorus in Lake Mendota are the waters below the thermocline and the input
      from storm sewers.

PMID- 16591846
TI  - A FURTHER ASSESSMENT OF THE ROLE OF FOUNDER EFFECTS IN THE OUTCOME OF Tribolium
      COMPETITION EXPERIMENTS.
AB  - A novel experimental design was employed to further investigate the importance of
      founder effects in determining the outcome of competition between the flour
      beetles Tribolium castaneum and T. confusum. Each of 10 replicate cultures in
      seven competition series was started with 10 pairs of adults of each species that
      were, in turn, the progeny of 1, 2, 4, 8, 16, 32, or 64 pairs of adults,
      respectively, from the foundation population. Thus the founder effect occurred
      one generation prior to the initiation of competition. An analysis of variability
      among replicate cultures for the first eight monthly censuses showed a
      significant increase in variation with smaller numbers of original pairs,
      confirming the hypothesis previously proposed to explain the indeterminate
      outcome of replicate competition cultures initiated with small numbers of
      founders. In addition, there was a significant reduction in the rate of
      elimination of T. confusum with smaller numbers of original pairs. It is
      suggested that T. castaneum is more sensitive to inbreeding, and that the
      differential response of the two populations to inbreeding reflects a difference
      in their homeostatic properties.

PMID- 16591847
TI  - Evidence for triplicate genes for alcohol dehydrogenase in hexaploid wheat.
AB  - The alcohol dehydrogenase zymogram phenotypes of 40 wheat strains, each
      possessing a distinctive chromosomal constitution, were determined. Genes
      involved in the production of alcohol dehydrogenase were located on the beta arm
      of chromosome 4A and on chromosomes 4B and 4D. The results support the hypothesis
      that the active alcohol dehydrogenase isozymes are dimers composed of the six
      possible combinations of subunits coded by triplicate structural genes.

PMID- 16591848
TI  - Application of I mossbauer effect to biological systems: studies with heme
      models.
AB  - The Mossbauer effect associated with (129)I, (125)Te, and (57)Fe has been applied
      to investigate structural properties of the axial ligands in ferric-high spin
      hematoheme-I, hematoheme-Te, and hematoheme-histidine-iodide. The magnitude and
      sign of the (129)I quadrupole coupling constant (e(2)qQ) and the isomer shift, as
      deduced from the Mossbauer effect spectra, are consistent with an axial, s-p
      hybridized bond of overwhelming sigma-character. Identical coupling constant
      (e(2)qQ((127)I) = -1826 +/- 3 MHz) were measured for both heme-I and hematoheme
      histidine-iodide. Implications of this result to the nature of ferric-high spin
      heme-histidine complexing are discussed. A stable heme (125)Te species formed in
      the electron-capture decay of heme-(125)I is observed, and structural properties
      of this singly bonded telluride ligand are discussed.

PMID- 16591849
TI  - Flows with cross sections.
AB  - Let M be a compact connected C(infinity)-manifold, of dimension n, without
      boundary. Let f(t): M --> M be a C(r)-flow with cross section. Let D(r)(M) be the
      topological group of diffeomorphisms of M with C(r)-topology (1 </= r </=
      infinity) and let D(o) (r)(M) be its connected component of the identity. Let
      [unk](M) be the group of I-cobordism classes in D(r)(M) generated by orientation
      preserving diffeomorphisms. For fepsilonD(r)(M) denote by [f] its I-cobordism
      class. Theorem 1 deals with the dependence of M(f) on [f]. Theorem 2: S(6) x S(1)
      has at least 28 distinct differentiable structures.Let x(o)epsilonS(1) and let
      [unk](r) be the set of C(r)-flows (r >/= 1) in M x S(1) with cross section M x
      {x(o)} and inducing in it the identity. Theorem 3: Intuitively to a loop in D(o)
      (r) based at the identity there corresponds a flow in [unk](r), and to homotopic
      loops correspond isotopic flows.COROLLARY. complete analysis of [unk](r)/ [unk]
      for dim M = 2.Theorems 4 and 5 refer to Anosov flows for dim M > 3.

PMID- 16591850
TI  - NATIONAL ACADEMY OF SCIENCES July 1, 1970.

PMID- 16591851
TI  - Correlation of isotope effects with molecular forces, I. The diatomic molecule.
AB  - The convergence properties of the individual terms in the finite orthogonal
      polynomial expansion of the partition function of a harmonic oscillator are
      examined as a function of the energy of the oscillator and the temperature of the
      system (u = epsilon/kT). The convergence of each term depends on the number of
      terms in the polynomial and the variable u. The jth term approaches within 1% of
      its asymptotic value when the order of the polynomial, n, equals (u/pi) + j +
      1.These favorable convergence properties of the finite polynomials are used to
      relate the partition function of an oscillator and the difference in chemical
      properties of isotopes directly to molecular and intermolecular forces. A
      detailed discussion is given for the diatomic molecule. In this case it is
      possible to treat the quantum corrections of any order in terms of a single
      particle function multiplied by kinetic energy-coupling factors. The latter are
      formulated as simple mass ratios of the order of unity.

PMID- 16591852
TI  - A class of neutral equations with the fixed point property.
AB  - For a neutral functional differential equation with a stable operator, D, it is
      shown that the solution operator is the sum of a contraction and a completely
      continuous operator.

PMID- 16591853
TI  - Deficient Photosystem II in Agranal Bundle Sheath Chloroplasts of C(4) Plants.
AB  - A method is described for separating mesophyll and bundle sheath chloroplasts
      from the leaves of C(4) plants. The agranal bundle sheath chloroplasts are
      inactive in the Hill reaction, whereas granal bundle sheath and granal mesophyll
      chloroplasts exhibit normal photosystem II activity. The agranal bundle sheath
      chloroplasts are deficient in photosystem II; they lack cytochrome b-559 and the
      fluorescence bands associated with photosystem II. All the chloroplasts exhibit
      photosystem I activity.

PMID- 16591854
TI  - Specific Assay for Differentiation in the Stalked Bacterium Caulobacter
      crescentus.
AB  - The bacterium Caulobacter crescentus carries out a distinct differentiation
      process during its life cycle. Cultures of the bacterium have been synchronized
      and an assay has been developed for monitoring the course of morphogenesis by the
      selective adsorption of radioactive RNA bacteriophage.

PMID- 16591855
TI  - Subelliptic estimates for complexes.
AB  - New results are announced linking properties of the symbol module and
      characteristic variety of a differential complex with test estimates near the
      characteristic variety of the type considered by Hormander ((1/2)-estimate). The
      first result is the invariance of the test estimates under pseudo-differential
      change of coordinates, and this leads to the introduction of a normal form for
      the complex in the neighborhood of a Cohen-MacCauley point of the symbol module.
      If the characteristic variety V is a manifold near the Cohen-MacCauley point
      (x(0),zeta(0)) with parametrizing functions p(1),...,p(q), where q is the
      codimension of the characteristic variety in the complexified contangent bundle,
      the matrix [Formula: see text] of Poisson brackets defines invariantly a
      Hermitian form Q on the normal space to V at (x(0),zeta(0)) when the
      dp(zeta)(x(0),zeta(0)) are used as basis, and the test estimates are satisfied at
      the ith stage of the complex if sig. Q (signature of Q) is >/= n - i + 1 (n the
      dimension of the base manifold) or rank Q - sig. Q >/= i + 1. Finally, conditions
      are given in order that, on a manifold with smooth boundary, the associated
      boundary complexes satisfy the (1/2)-estimate.

PMID- 16591856
TI  - Inference from Inadequate and Inaccurate Data, III.
AB  - Having measured D numerical properties of a physical object E which requires many
      more than D parameters for its complete description, we want to estimate P other
      numerical properties of E. Continuing the discussion in papers I(1) and II,(2)
      the present paper gives estimates when we believe it likely that we can guess an
      upper bound M on the Hilbert norm not of h(E), the model representing E in some
      Hilbert space, but of the orthogonal projection of h(E) onto a sufficiently large
      subspace. In addition, the present paper simplifies the notation of I, and makes
      explicit the application of Bayesian subjective probability when there are errors
      in the data and we want to find the joint probability distribution of more than
      one prediction.

PMID- 16591857
TI  - Measure-theoretic properties of arbitrary point sets.
AB  - Consider an arbitary point set S on the real number line or in Euclidean n-space
      (the limitation to Euclidean space is unessential). The set S has an interior
      Lebesgue measure m(i)(S) and an exterior Lebesgue measure m(e)(S). There are the
      following well known inequalities for two disjoint sets S(1) and S(2):
      m(i)(S(1)US(2)) [unk] m(i)(S(1)) + m(i)(S(2)), m(e)(S(1)US(2)) </= m(e)(S(1)) +
      m(e)(S(2)). These state the superadditivity of interior measure for disjoint
      sets, and the subadditivity of exterior measure. The question is posed as to what
      conditions, besides these, are there on the six quantities m(i)() and m(e)() for
      the disjoint sets S(1),S(2) and for their union S(1)US(2).The present paper
      obtains a complete set of conditions on these six quantities. These are in the
      form of inequalities. The variability can be expressed in terms of six
      independent nonnegative quantities, and the six quantities m(i)() and m(e)() for
      the disjoint sets S(1), S(2) and for S(1)US(2) can be expressed as suitable sums
      of these.There appears the interesting property that the "average measure"
      m(a)(S), defined by m(a)(S) = (m(i)(S) + m(e)(S))/2, is subadditive. Also, any
      linear combination alpham(i)(S) + betam(e)(S) is discussed.

PMID- 16591858
TI  - Superconductivity: the transition temperature peak below four electrons per atom.
AB  - It is shown that the superconducting transition temperature for compounds in
      seven different structure types exhibits a peak at about 3.7 to 3.9 valence
      electrons per atom.

PMID- 16591859
TI  - On existence theorems for nonlinear equations involving noncompact mappings.
AB  - In this note we present two new theorems concerning the solvability of nonlinear
      equations in normed linear spaces involving either K-coercive pseudo-A-proper
      mappings (Theorem 1) or their uniform limits (Theorem 2). These theorems are then
      used to obtain certain known as well as new existence results for various special
      classes of equations involving, for example, A-proper and P-compact operators; K
      monotone, quasi-K-monotone and pseudo-K-monotone operators; monotone and others.

PMID- 16591860
TI  - Overt and covert effects of endogenous and exogenous ecdysone in puparium
      formation of flies.
AB  - Mature larvae of Sarcophaga argyrostoma fail to form puparia when kept in contact
      with water, but pupariate after having been subsequently exposed to dryness for
      30 hr. They become increasingly more sensitive to injected ecdysone the longer
      the exposure to dry conditions. A second wet treatment halts the production of
      hormone that had occurred during the dry period, and reduces a sensitization to
      injected ecdysone during the intervening dry treatment. Apparently, injected
      ecdysone had cumulative effects not with the endogenous or exogenous hormone, but
      with its covert effects which had arisen during the dry period and persisted
      throughout the second wet period. The hind parts of larvae ligated at the end of
      a wet period pupariate when injected with either one massive dose of ecdysone, or
      a far smaller total of several subsequent doses. In the case of two unequal
      doses, the effect was greater when the smaller dose was injected first. In order
      to get pupariation with minimal effective doses, a continuous supply of the
      hormone during a certain period is required. It is suggested that the inhibition
      of pupariation by moisture has arisen as an adaptation to unfavorable conditions.

PMID- 16591861
TI  - A capillarity mechanism for diatom gliding locomotion.
AB  - It is proposed that the diatom raphe is a parallel-plate capillary containing a
      fluid which reacts at the trailing end, turning into a form which no longer
      "wets" the raphe walls, and which is left behind as a trail. More unreacted raphe
      fluid is drawn by capillary pressure from a source near the leading end of the
      raphe. This fluid sticks out from the raphe along its length, adhering to
      surfaces, thus causing gliding locomotion. Formulae are given for the maximum
      velocity and force of a moving diatom in terms of the raphe dimensions and the
      surface tension and viscosity of the fluid. An a priori estimate of the force
      exerted by a moving diatom, 1-50 millidynes, agrees with measured values. Five
      experimental tests of the theory are proposed.

PMID- 16591862
TI  - On a third kind of characteristic numbers of the spheroidal functions.
AB  - A set of real positive numbers gamma(alphan)(c) was found recently to be
      associated with the spheroidal functions of real order alpha > -1 as a
      consequence of their double orthogonality on (-1, 1) and (- infinity, infinity).
      In the range -1 < alpha < 0 these numbers are shown to be determined by the
      eigenvalues of a new integral equation for the spheroidal functions. Thus they
      represent a third kind of characteristic numbers. The new equation ceases to be
      an integral equation above the range -1 < alpha < 0 but it leads to computational
      formulas for gamma(alphan)(c) that appear from numerical results to be valid for
      all real alpha > -1.

PMID- 16591863
TI  - A Perturbation Series for Cauchy's Problem for Higher-Order Abstract Parabolic
      Equations.
AB  - The application of Phillips' perturbation theorem to Cauchy's problem for higher
      order parabolic equations is justified by an argument from the theory of Fourier
      transforms of entire functions.

PMID- 16591864
TI  - The "transformation" from marxian "values" to competitive "prices": a process of
      rejection and replacement.
AB  - The well-known transformation procedure for transforming from Marxian values to
      competitive prices is shown to be logically of the form: "Anything" equals
      "anything else" multiplied by "anything/anything else."

PMID- 16591865
TI  - Crystal and molecular structure of n,n'-diethyl-n,n'-diphenylurea.
AB  - N,N'-diphenyl-N,N'-diethylurea (C(17)H(20)N(2)O) crystallizes in the space group
      P2(1)/c. The unit cell constants are: a = 10.42 +/- 0.01 A, b = 16.86 +/- 0.02 A,
      c = 10.66 +/- 0.001 A, beta = 125 degrees 16' +/- 5'; Z = 4, D(x) = 1.16 g.cm(
      3), D(meas) = 1.16 +/- 0.01 g.cm(-3). Data for 1392 reflections were collected at
      room temperature on a Picker automated diffractometer. The crystal structure was
      solved by direct methods and refined by bloc-diagonalized matrix least-squares
      calculations. The molecule is characterized by a pseudo C(2) symmetry; both
      phenyl groups are trans with respect to the oxygen atom. The hybridization of the
      two nitrogen atoms is intermediate between trigonal and tetrahedral; the
      nonplanar distortion of the amide groups is about 30 degrees . The amide C-N bond
      lengths are 1.37 A.

PMID- 16591866
TI  - Differentiable cohomology on locally compact groups.
AB  - In this paper the notions of vector field and differential form are extended to
      locally compact groups which are the inverse limit of Lie groups. This is done
      using Bruhat's definition of [unk](c) (infinity) functions on such a group.
      Vector fields are defined as derivations on the [unk](c) (infinity) functions.
      Then tangent vectors at a point are defined as elements of the inverse limit of
      the tangent spaces of the Lie groups. Tangent vectors then are put together to
      form vector fields, corresponding to a bundle definition, and the two notions are
      shown to be equivalent. Differential forms are defined using a bundle type
      definition from continuous linear functional on the tangent space. An existence
      and uniqueness theorem is proven for the exterior differential. Then an analog of
      the Poincare lemma leads to the de Rham theorem relating the Cech cohomology with
      real coefficients to the cohomology of the differential forms.

PMID- 16591867
TI  - Electron-Nuclear Double Resonance of a Protein That Contains Copper: Evidence for
      Nitrogen Coordination to Cu(II) in Stellacyanin.
AB  - Electron-nuclear double resonance has been used to study ligand hyperfine
      interactions of the copper (II) complex in a frozen solution of the blue protein
      stellacyanin. It is shown that the copper ion coordinates with at least one
      nitrogen ligand, and probably more than one, and that the copper ion is in a
      hydrophobic environment.

PMID- 16591868
TI  - Biology of the Precambrian Genus Kakabekia: New Observations on Living Kakabekia
      barghoorniana.
AB  - Kakabekia barghoorniana Siegel, living species of a fossil genus Kakabekia, has
      now been cultured from Alaskan soil samples obtained from the Mendenhall Glacier
      near Juneau and from the Point Barrow region above the Arctic Circle.
      Morphological comparisons, especially of mantle variations, show that fossil and
      living populations overlap in many details. Cytochemical tests demonstrate that
      living Kakabekia has no storage forms of lipid or polysaccharide and no
      phenoloxidase. Some individuals (19-33%) contain heme enzymes but most do not;
      hence they cannot utilize O(2) even in air.

PMID- 16591869
TI  - A generating function for certain coefficients involving several complex
      variables.
AB  - In an attempt to unify a number of generating functions for certain classes of
      generalized hypergeometric polynomials, Lagrange's expansion formula is applied
      to prove a generating relation for an n-dimensional polynomial with arbitrary
      coefficients. It is also shown how these coefficients can be specialized to
      obtain the generalized Lauricella function as a generating function for a class
      of generalized hypergeometric polynomials of several complex variables.

PMID- 16591870
TI  - On the Fundamental Group of Manifolds of Non-positive Curvature.
AB  - We prove theorems on the structure of the fundamental group of a compact
      riemannian manifold of non-positive curvature. In particular, a conjecture of J.
      Wolf [J. Differential Geometry, 2, 421-446 (1968)] is proved.

PMID- 16591871
TI  - Ecological consequences of island colonization by southwest pacific birds, I.
      Types of niche shifts.
AB  - The land and fresh-water birds of the southwest Pacific islands derive mainly
      from New Guinea and offer a favorable situation for studying ecological
      consequences of island invasions. The reduction of competition on species-poor
      islands permits some colonizing species to expand their niches spatially, by
      occupying altitudinal bands, types of habitats, and/or vertical strata of the
      forest from which they are excluded by other species on species-rich islands.
      Expansions to higher altitudes, or from second-growth into forest, are especially
      frequent. Other colonists become more abundant in the same type of habitat
      preferred on New Guinea. Instances of a change in diet are rare. Changes in
      foraging technique are noted mainly for those colonists that have been isolated
      long enough to have undergone morphological divergence. Approximately half of the
      colonizing populations experience no niche shift.

PMID- 16591872
TI  - Loss due to missing data in efficiency of a locally optimal test for homogeneity
      with respect to very rare events.
AB  - With reference to observations of supernovae in galaxies, a locally optimal test
      for the hypothesis of homogeneity of the observational units with respect to
      occurrence of supernovae (treated as a very rare event) is obtained for the case
      where the data are available only for those galaxies where at least one supernova
      is observed. It is shown that the loss in the asymptotic efficiency of the test
      due to lack of reporting of galaxies with no supernovae is very heavy and in fact
      is infinite for the case of very rare events.

PMID- 16591874
TI  - Symposium on AIDS and threats to society from technology: foreword.

PMID- 16591873
TI  - The pi-Cation Radical of Chlorophyll a.
AB  - Chlorophyll a undergoes reversible one-electron oxidation in dichloromethane and
      butyronitrile. Removal of the electron by controlled potential electrolysis or by
      stoichiometric charge transfer to a known cation radical yields a radical (epr
      line width = 9 gauss, g = 2.0025 +/- 0.0001) whose optical spectrum is bleached
      relative to that of chlorophyll. Upon electrophoresis this bleached species
      behaves as a cation. By comparison with the known properties of pi-cation
      radicals of porphyrins and chlorins, the chlorophyll radical is also identified
      as a pi-cation. Further correlation of optical and epr properties with published
      studies on photosynthesis leads to the conclusion that oxidized P700, the first
      photochemical product of photosystem I in green plants, contains a pi-cation
      radical of the chlorin component of chlorophyll a. This radical is the likely
      source of the rapidly-decaying, narrow epr signal of photosynthesis.

PMID- 16591875
TI  - Priorities of attack on urban problems.

PMID- 16591876
TI  - Recent technological developments in industrialized production of housing.

PMID- 16591877
TI  - A property of legendre polynomials.

PMID- 16591878
TI  - Role of heterogeneity of the solvation site in electronic spectra in solution.
AB  - The emission spectra of polar aromatic molecules in rigid, polar solution are
      shown to depend on the exciting wavelength. Occurrence of the phenomenon depends
      on both the excited-state lifetime of the chromophore and the degree of rigidity
      of the medium. The results are interpreted in terms of a model which stresses the
      contribution of micro-environmental heterogeneity to electronic absorption and
      emission spectra.

PMID- 16591879
TI  - Note on degree of convergence of sequences of rational functions of prescribed
      type.
AB  - This note studies the degree of convergence of various sequences of rational
      functions of given types which are of best approximation to a given function
      analytic on a given point set and meromorphic on a larger set. The sequences are
      conveniently represented by the analog of the Pade table.

PMID- 16591880
TI  - On finitely additive vector measures.
AB  - In this paper we extend the well-known Vitali-Hahn-Saks and Nikodym theorems for
      measures to finitely additive vector-valued set functions.

PMID- 16591881
TI  - Evidence from chloroplast fragments for three photosynthetic light reactions.
AB  - Previous reports from this laboratory described a new concept of three light
      reactions in plant photosynthesis comprising two short-wavelength (lambda < 700
      nm) photoreactions belonging to Photosystem II and one long-wavelength (lambda >
      700 nm) photoreaction belonging to Photosystem I. Among the electron carriers
      assigned to Photosystem II were cytochrome b(559) and plastocyanin and to
      Photosystem I, cytochrome f.According to a widely held view, the light-induced
      reduction of NADP by water requires the collaboration of Photosystems I and II
      and involves specifically cytochrome f and P700 (a portion of chlorophyll a
      peculiar to Photosystem I). By contrast, the new concept ascribes the light
      induced reduction of NADP by water solely to the two photoreactions of
      Photosystem II, without the participation of Photosystem I and its components,
      cytochrome f and P700.Further evidence in support of the new concept has now been
      obtained from chloroplast fragments. Two kinds of chloroplast fragments have been
      prepared: (a) one with Photosystem II activity, capable-in the presence of
      plastocyanin-of photoreducing NADP with water but lacking P700 and functional
      cytochrome f and (b) another having only Photosystem I activity, lacking
      plastocyanin, and enriched in P700.

PMID- 16591882
TI  - Law of conservation of the capital-output ratio.
AB  - Just as simple harmonic motion, definable by a variational condition, delta [unk]
      ((1/2) x(2) - (1/2) x(2)) dt = 0, has motions which must conserve the sum of
      kinetic and potential energies, (1/2) x(2) + (1/2)x(2) congruent with constant,
      so in a neoclassical von Neumann economy, where all output is saved to provide
      capital formation for the system's growth, it will be true that there exists a
      conservation law-namely the constancy along any intertemporally-efficient motion
      of the capital-output ratio SigmaP(t) (j)K(t) (j)/SigmaP(t) (j)K(t) (j). This is
      derived as an "energy" integral of a time-free integrand(1) in an optimal-control
      problem of variational type.

PMID- 16591883
TI  - Darboux problem for a polyvibrating equation: solution as an f-equation.
AB  - In this paper we investigate a Darboux problem for a polyvibrating equation with
      analytic data. It is solved by the F-function approach of C. Truesdell, extending
      his F-equations to functions with several variables.

PMID- 16591884
TI  - Photodestruction of chloroplast ultrastructure by red light: location of
      chlorophyll.
AB  - A lethal dose (1 Mrad) of gamma rays was given to wheat leaf tissue to restrict
      migration of the energy of red light photoexcitation to the photosynthetic
      pigment system. This dose of gamma radiation had no apparent effect on
      chloroplast ultrastructure in tissue that received no illumination. Subsequent
      illumination with red light, used to induce chlorophyll-sensitized
      photodestruction of ultrastructure, permitted inferences about the location of
      chlorophyll within the chloroplast. The red light produced extensive disruption
      in chloroplasts but not in any other cellular organelles. The sequence of events
      in this photodestruction was different from that which occurs when chloroplasts
      are destroyed by methods that do not involve illumination. The red light caused
      peculiar abnormalities only in the internal lamellar system of the chloroplast
      and not in the envelope or any other regions. These findings support other
      studies which suggest that chlorophyll is located exclusively in grana and stroma
      lamellae.

PMID- 16591885
TI  - Mutations Altering Chloroplast Ribosome Phenotype in Chlamydomonas, II. A New
      Mendelian Mutation.
AB  - A new mutation of Chlamydomonas reinhardi, cr-1, is characterized. The mutation
      exhibits Mendelian inheritance and affects the sedimentation velocity and
      formation of intact chloroplast ribosomes. The mutant grows reasonably well when
      supplied with sodium acetate as a carbon source, but poorly when forced to grow
      photosynthetically using carbon dioxide. Since the mutant cr-1 accumulates large
      subunits of the chloroplast ribosome, we postulate that it is blocked in the
      formation of the small subunit. A tentative model explaining the behavior of the
      several mutants in Chlamydomonas now known to have altered chloroplast ribosomal
      phenotypes is presented.

PMID- 16591886
TI  - Nuclear Magnetic Resonance Spectroscopy. Variable-Temperature C and F Study of
      the Chair-Chair Interconversion of 1,1,3,3-Tetramethylcyclohexane and gem
      Difluoro-1,1,3,3-Tetramethylcyclohexanes.
AB  - A variable-temperature, proton noise-decoupled, (13)C nmr spectral study of the
      chair-chair interconversion in 1,1,3,3-tetramethylcyclohexane has demonstrated
      the utility of (13)C spectra for probing conformational equilibria. There is a
      much larger chemical-shift difference between the carbons of axial and equatorial
      methyl groups than between the protons of these methyl groups, 133 Hz compared to
      7.5 Hz. Comparison of the activation parameters determined from the (13)C spectra
      of 1,1,3,3-tetramethylcyclohexane with those determined from a variable
      temperature (19)F study on 2,2,6,6-tetramethyl-1,1-difluorocyclohexane shows that
      the introduction of a gem-difluoro group into the ring causes significant steric
      interactions. The (13)C chemical shifts for 1,1,3,3-tetramethylcyclohexane
      reflect the importance of the methyl-methyl 1,3-diaxial interactions.

PMID- 16591887
TI  - Protein Chain-Initiating Methionine tRNAs in Chloroplasts and Cytoplasm of Wheat
      Leaves.
AB  - The role of methionine in protein chain initiation in wheat has been studied. Two
      chain-initiating methionine tRNAs have been found. One of these is located in the
      cytoplasm of the wheat cell. This methionyl-tRNA is not formylated by wheat
      extracts and appears to function in protein chain initiation in the cytoplasm
      without prior formylation. The other initiating tRNA is from chloroplasts. This
      methionyl-tRNA is formylated by a transformylase present in wheat extracts and
      functions in chain initiation in chloroplasts as formylmethionyl-tRNA.

PMID- 16591888
TI  - Nuclear Magnetic Resonance Spectroscopy. A Stereospecific J(CF) Coupling in the
      Low-Temperature C Nmr Spectrum of 1,1-Difluorocyclohexane.
AB  - The proton-decoupled (13)C nmr spectrum of 1,1-difluorocyclohexane has been
      examined at room temperature and at -90 degrees C. There are only minor changes
      in the one-bond and two-bond carbon-fluorine scalar coupling constants at the
      lower temperature; however, the triplet observed for C-3 ((3)J(CF) = 4.7 Hz)
      collapses to a doublet ((3)J(CF) = 9.5 Hz) at -90 degrees C. It is proposed that
      only the equatorial fluorine is coupled with the C-3 carbon as the result of
      operation of a back-lobe orbital interaction.

PMID- 16591889
TI  - Current induced in a plasma by a penetrating electron beam.
AB  - The passage of a single pulse of relativistic electrons through a plasma is
      considered, and the total current in the axial direction it induces in the plasma
      is calculated. This calculation is valid for an injected beam current density
      that has arbitrary functional dependence on the radial and azimuthal coordinates.
      For the special case of a beam current density that is uniform in the radial
      direction out to the beam radius a, these results agree with results of others
      published previously.This calculation is simple because the equation for the
      variation with time of the plasma charge density at any point, independent of
      what happens at other points, is only slightly more complicated than the familiar
      equation for an ohmic conduction.

PMID- 16591890
TI  - Configuration Interaction in the Calculation of Oscillatory and Rotatory
      Intensities of Nonplanar pi-Electronic Systems.
AB  - The interaction of configurations, including all possible singly excited
      configurations, is incorporated into the calculation of oscillatory and rotatory
      intensities of simple nonplanar pi-electronic systems such as skewed butadiene
      and acrolein. The results are discussed in terms of the reliability of the (self
      consistent field)-(linear combination of atomic orbitals)-(molecular orbital)
      wave functions employed.

PMID- 16591891
TI  - Embedding trees in the rationals.
AB  - An example is presented of a simple algebraic statement whose truth cannot be
      decided within the framework of ordinary mathematics, i.e., the statement is
      independent of the usual axiomatizations of set theory. The statement asserts
      that every tree-like ordering of power equal to or less than the first
      uncountable cardinal can be embedded homomorphically into the rationals.

PMID- 16591892
TI  - One- and two-fluid van der waals theories of liquid mixtures, I. Hard sphere
      mixtures.
AB  - The equation of state of a mixture of hard spheres is calculated using the one-
      and two-fluid van der Waals theories and the three-fluid theory. The one-fluid
      theory is found to be in the best agreement with the machine-simulation results.

PMID- 16591893
TI  - A negative partition relation.
AB  - If the continuum hypothesis is assumed, there is a graph G whose vertices form an
      ordered set of type omega(1) (2); G does not contain triangles or complete even
      graphs of form [[unk](0),[unk](0)], and there is no independent subset of
      vertices of type omega(1) (2).

PMID- 16591894
TI  - Further studies of the whitetop cloud-seeding experiment.
AB  - By means of two stratifications of experimental days of the Whitetop Project-into
      categories E and W and into categories air mass and frontal-the effects of cloud
      seeding on precipitation downwind, upwind, and to the sides, up to 180 miles from
      the seeding line, were investigated. No significant effects were found for W and
      frontal days. On the other hand, for E and airmass days, significant and highly
      significant apparent effects of seeding were found in all directions and in areas
      at distances up to 180 miles. All these significant apparent effects are
      negative, the largest of them indicating that seeding reduced precipitation to
      one quarter of its unseeded value.

PMID- 16591895
TI  - Stability of Plane Poiseuille Flow to Periodic Disturbances of Finite Amplitude,
      II.
AB  - The stability of plane Poiseuille flow to periodic disturbances of finite
      amplitude was investigated by expanding each harmonic of the solution in terms of
      the Orr-Sommerfeld eigenfunctions with coefficients which are functions of time.
      The system of nonlinear ordinary differential equations for the coefficients was
      solved, and the number of harmonics N was extended from 3, of the previous
      investigation, to 5. The shift in the neutral curve in going from N = 3 to N = 5
      is considerable, indicating insufficient convergence. The higher-order harmonics
      are effective because the zone of mode-coalescence rises with increasing N.

PMID- 16591896
TI  - Lacunarity for compact groups.
AB  - Let G be a compact Abelian group with character group X. A subset Delta of X is
      called a [unk](q) set (1 < q < infinity) if for all trigonometric polynomials f =
      [unk](k=1) (n) alpha(k)chi(k) (chi(1),...,chi(n) [unk] Delta) an inequality
      parallelf parallel(q) [unk] [unk] parallelf parallel(1) obtains, where [unk] is a
      positive constant depending only on Delta. The subset Delta is called a Sidon set
      if every bounded function on Delta can be matched by a Fourier-Stieltjes
      transform. It is known that every Sidon set is a [unk](q) set for all q. For G =
      T, X = Z, Rudin (J. Math. Mech., 9, 203 (1960)) has found a set that is [unk](q)
      for all q but not Sidon. We extend this result to all infinite compact Abelian
      groups G: the character group X contains a subset Delta that is [unk](q) for all
      q, 1 < q < infinity, but Delta is not a Sidon set.

PMID- 16591897
TI  - Instabilities of high temperature superconductors.
AB  - We have observed the transition temperature of both the cubic and tetragonal
      phases of several high-temperature beta-W superconductors. The instability of the
      cubic lattice appears to be characteristic of high-temperature superconductors.

PMID- 16591898
TI  - Solution of the time-dependent schrodinger equation by the laplace transform
      method.
AB  - The time-dependent Schrodinger equation for two quite general types of
      perturbation has been solved by introducing the Laplace transforms to eliminate
      the time variable. The resulting time-independent differential equation can then
      be solved by the perturbation method, the variation method, the variation
      perturbation method, and other methods.

PMID- 16591899
TI  - Germination and growth of neurospora at low water activities.
AB  - When the water activity (a(w)) of the medium is lowered by the addition of NaCl
      or nonelectrolytes, an inhibition of germination, growth rate, and total growth
      is observed in Neurospora crassa. Inhibition of conidial germination is separable
      from the other effects and is caused, in large measure, by the loss from conidia
      in media of low water activity of a substance that is essential for their
      germination. The substance is detectable in the medium and is also extractable
      from cultures. It is dialysable and thermostable, and it appears to be highly
      active. It is not detectable in complete medium.

PMID- 16591900
TI  - Synthetic derivatives of polyethyleneimine with enzyme-like catalytic activity
      (synzymes).
AB  - A synthetic polymer has been prepared which contains dodecyl groups (to bind
      small substrate molecules) and methyleneimidazole side chains (as nucleophilic
      catalytic sites) linked to a polyethyleneimine framework. This macromolecule,
      with a high local concentration of binding and catalytic groups, catalyzes the
      hydrolysis of uncharged nitrophenyl esters in water at pH 7 with rates markedly
      greater than previously observed with any other synthetic substances under
      similar conditions.

PMID- 16591901
TI  - Cyanophycin Granules from the Blue-Green Alga Anabaena cylindrica: A Reserve
      Material Consisting of Copolymers of Aspartic Acid and Arginine.
AB  - The cyanophycin granules from two-week-old cultures of the blue-green alga
      Anabaena cylindrica were isolated by sonication of the cells followed by
      differential centrifugation. These particles are composed of polypeptides
      containing only two amino acids, aspartic acid and arginine, and have a molecular
      weight between about 25,000 and 100,000.

PMID- 16591902
TI  - Optimal solutions to a linear inverse problem in geophysics.
AB  - This paper is concerned with the solution of the linear system obtained in the
      Backus-Gilbert formulation of the inverse problem for gross earth data. The
      theory of well-posed stochastic extensions to illposed linear problems, proposed
      by Franklin, is developed for this application. For given estimates of the
      statistical variance of the noise in the data, an optimal solution is obtained
      under the constraint that it be the output of a prescribed linear filter. Proper
      specification of this filter permits the introduction of information not
      contained in the data about the smoothness of an acceptable solution. As an
      example of the application of this theory, a preliminary model is presented for
      the density and shear velocity as a function of radius in the earth's interior.

PMID- 16591903
TI  - Stochastic speculative price.
AB  - Because a commodity like wheat can be carried forward from one period to the
      next, speculative arbitrage serves to link its prices at different points of
      time. Since, however, the size of the harvest depends on complicated probability
      processes impossible to forecast with certainty, the minimal model for
      understanding market behavior must involve stochastic processes. The present
      study, on the basis of the axiom that it is the expected rather than the known
      for-certain prices which enter into all arbitrage relations and carryover
      decisions, determines the behavior of price as the solution to a stochastic
      dynamic-programming problem. The resulting stationary time series possesses an
      ergodic state and normative properties like those often observed for real-world
      bourses.

PMID- 16591904
TI  - Terrestrial and meteorite carbon appear to have the same isotopic composition.
AB  - The carbon-isotope ratio recently obtained for the carbon found in the Murchison
      meteorite, which has been shown (by the racemic nature of twelve component amino
      acids) to be free of terrestrial contamination, agrees with that for average
      terrestrial sediments. This finding indicates that the earth and the stony
      meteorites contain carbon of the same isotopic composition.

PMID- 16591905
TI  - The characters of the symmetric group.
AB  - A short and simple derivation of the formula of Frobenius, which gives the
      dimensions of the irreducible representations of S(n), the symmetric group on any
      number, n, of symbols, is given. These dimensions are the characters of the
      identity element of the group, i.e., of the element all of whose cycles are
      unary. It is shown how a slight modification of Frobenius' formula yields, when n
      = 2p is even, the characters of an element of S(n) all of whose cycles are binary
      and, when n = 3p is a multiple of 3, the characters of an element of S(n) all of
      whose cycles are ternary and, generally, when n = kp is a multiple of any
      positive integer k, the characters of an element of S(n) all of whose cycles are
      of length k. It is noteworthy that the calculations become simpler, rather than
      more complicated, as k increases. Finally, this paper shows how to derive from
      Frobenius' formula the characters of an element of S(n) which has at least one
      unary cycle and, from the present modifications of Frobenius' formula, the
      characters of an element of S(n) which has at least one cycle of length k, k = 2,
      3,..., n.

PMID- 16591906
TI  - Calculation of the reaction cross section from a rate constant by the method of
      steepest-descent.
AB  - The reaction cross section of a bimolecular reaction has been calculated from the
      corresponding rate constant by the inverse Laplace transform. In carrying out the
      inverse Laplace transform, the method of steepest-descent has been used. As
      applications, the reaction cross sections for the rate constant of k(T) = k'
      T(n)e(-E0/kT) and for the rate constant of the absolute reaction rate theory have
      been calculated. The computation of the energy density function associated with
      the definition of the weighted-average cross section has also been discussed.

PMID- 16591907
TI  - Induction of Staphylococcus aureus Lactose Permease in the Absence of
      Glycerolipid Synthesis.
AB  - Glycerol auxotrophs of S. aureus were isolated and shown to cease phospholipid
      synthesis immediately when deprived of glycerol. Second-step mutants with
      temperature-sensitive inducibility of the lac system were also isolated. When
      cells were induced by temperature shift to produce the products of the lac system
      in the absence of glycerol, the permease activity, relative to 6-phospho-beta
      galactosidase activity, was between 30 and 50% that of glycerol-supplemented
      cultures. However, the phosphotransferase activity for beta-galactosides in
      isolated membranes was found to be normal when compared to the level of beta
      galactosidase. This indicated that the permeation system was induced and
      integrated into the membrane, but did not function efficiently for transport.
      Readdition of glycerol in the presence of chloramphenicol resulted in a slow
      increase in efficiency of the transport activity. Glycerol deprivation after
      induction led to a small loss of permease efficiency.

PMID- 16591908
TI  - Nonprotein amino acids in the murchison meteorite.
AB  - Twelve nonprotein amino acids appear to be present in the Murchison meteorite.
      The identity of eight of them has been conclusively established as N
      methylglycine, beta-alanine, 2-methylalanine, alpha-amino-n-butyric acid, beta
      amino-n-butyric acid, gamma-amino-n-butyric acid, isovaline, and pipecolic acid.
      Tentative evidence is presented for the presence of N-methylalanine, N
      ethylglycine, beta-aminoisobutyric acid, and norvaline. These amino acids appear
      to be extraterrestrial in origin and may provide new evidence for the hypothesis
      of chemical evolution.

PMID- 16591909
TI  - Performance of an automated computerized plate scanner.
AB  - A brief summary is given of the initial performance of an automated computerized
      plate-measuring machine, and it is seen that the machine is working entirely
      satisfactorily.

PMID- 16591910
TI  - The weierstrass-laguerre transform.
AB  - An elegant expression is obtained for the product of the inverse Weierstrass
      Laguerre transforms of two functions in terms of their convolution. It is also
      shown how the main result can be extended to hold for the product of the inverse
      Weierstrass-Laguerre transforms of several functions.

PMID- 16591911
TI  - Photocatalytic Production of Organic Compounds from CO and H(2)O in a Simulated
      Martian Atmosphere.
AB  - [(14)C]CO(2) and [(14)C]organic compounds are formed when a mixture of [(14)C]CO
      and water vapor diluted in [(12)C]CO(2) or N(2) is irradiated with ultraviolet
      light in the presence of soil or pulverized vycor substratum. The [(14)C]CO(2) is
      recoverable from the gas phase, the [(14)C]organic products from the substratum.
      Three organic products have been tentatively identified as formaldehyde,
      acetaldehyde, and glycolic acid. The relative yields of [(14)C]CO(2) and
      [(14)C]organics are wavelength- and surface-dependent. Conversion of CO to CO(2)
      occurs primarily at wavelengths shorter than 2000 A, apparently involves the
      photolysis of water, and is inhibited by increasing amounts of vycor substratum.
      Organic formation occurs over a broad spectral ranger below 3000 A and increases
      with increasing amounts of substratum. It is suggested that organic synthesis
      results from adsorption of CO and H(2)O on surfaces, with excitation of one or
      both molecules occurring at wavelengths longer than those absorbed by the free
      gases. This process may occur on Mars and may have been important on the
      primitive earth.

PMID- 16591912
TI  - Subordinate quadratic forms and their complementary forms.
AB  - Theorem 1. For alpha, beta on the range 1,..., mu, let Q(z) =
      (*)aalphabetazalphazbeta be a real valued, nonsingular, symmetric quadratic form.
      For positive integers r and s such that mu = r + s set (z(1),..., z(mu)) =
      (u(1),..., u(r):S(1),..., S(n)), Q(z) = P(u, s) and [Formula: see text] Let B =
      (z((1)),..., z((r))) be a base "over R" for points z epsilon pi(r). For an
      arbitrary r-tuple omega(1),..., omega(r) set [Formula: see text] index
      H(B)(omega) = kappa and nullity H(B)(omega) = nu. Then [Formula: see text].

PMID- 16591913
TI  - One- and Two-Fluid van der Waals Theories of Liquid Mixtures, II. 6:12 Molecules.
AB  - The equation of state of mixture of 6:12 molecules is calculated using the one-
      and two-fluid van der Waals theories, the three-fluid theory, and the Flory
      theory. The one-fluid van der Waals theory is found to be in the best agreement
      with the quasi-experimental, machine-simulation results.

PMID- 16591914
TI  - Evidence of widespread effects of cloud seeding at two Arizona experiments.
AB  - The average effect of two cloud seeding experiments (1957-1960; 1961, 1962, and
      1964) over the Santa Catalina Mountains, Arizona, on the 24-hr precipitation at
      Walnut Gulch, 65 miles away, was an apparent 40% loss of rainfall (P = 0.025) on
      seeded, as opposed to not-seeded, experimental days. Larger apparent losses, some
      highly significant, were found for experimental days on which Walnut Gulch was
      downwind from the seeding site (but not on upwind days), and also on "second
      days" of the randomized pairs (but not on "first days"). The timing of
      significant apparent effects indicated that the afternoon maximum of
      precipitation, which is very pronounced on days without seeding, is either absent
      or weakened on days with seeding. This phenomenon was observed earlier in a study
      of the Whitetop Project.

PMID- 16591915
TI  - On the concept of orbital steering in catalytic reactions.
AB  - Angular displacement from linear overlap of but a few degrees in the transition
      state of the enzyme-substrate complex has been postulated to be of great kinetic
      significance ("orbital steering"). The concept of orbital steering is shown to
      have evolved from the orientation parameters of an equation previously proposed
      to evaluate the kinetic importance of propinquity. This equation is shown to be
      naive. Arguments provided against the concept of orbital steering include: (a)
      force constants predicted from orbital steering are about 100 times those
      experimentally determined from displacement of nuclei in a direction normal to
      the axis of a covalent bond (for example, at room temperature vibrational bending
      amplitudes of +5 degrees or more are common); (b) because of the lessened
      directionality of orbitals containing nonbonded electron pairs, the force
      constants in transition states should be even smaller than in the case of a
      covalent bond; and (c) molecular orbital calculations predict shallow total
      energy minima for orbital alignment. The experimental rate data offered as a
      basis for the concept of orbital steering are shown to find rationalization in
      the previously observed dependence of DeltaSdouble dagger on kinetic order and
      the energy requirements for the freezing-out of single bonds in the transition
      state leading to the formation of medium-size ring compounds from extended ground
      states. It is concluded that if orbital steering does exist, experimental and
      theoretical evidence to support this concept have yet to be presented.

PMID- 16591916
TI  - Some cohomology classes in principal fiber bundles and their application to
      riemannian geometry.
AB  - We define some new global invariants of a fiber bundle with a connection. They
      are cohomology classes in the principal fiber bundle that are defined when
      certain characteristic curvature forms vanish. In the case of the principal
      tangent bundle of a riemannian manifold, they are invariant under a conformal
      transformation of the metric. They give necessary conditions for conformal
      immersion of a riemannian manifold in euclidean space.

PMID- 16591917
TI  - Differentiable pseudo-free circle actions.
AB  - The circle group G is said to act pseudofreely if it is not free and if every
      orbit is one-dimensional and if the isotropy group is the identity except on
      isolated exceptional orbits where the isotropy group is the finite cyclic group
      Z(k), k > 1. We consider differentiable actions of this kind on homotopy seven
      spheres and classify all such actions. As a corollary, it follows that there can
      be any finite number of exceptional orbits, in contrast to the linear case where
      there can be at most four.

PMID- 16591918
TI  - Improvements in tests of long-range charge independence.
AB  - The procedure used to determine the pionnucleon coupling constant g(2) from multi
      energy fits to nucleon-nucleon (N-N) scattering data has been shortened without a
      material loss of accuracy. The g(2) presetting effect is discussed in connection
      with the limited accuracy of g(2) determinations in general and the possibilities
      of the "optimized polynomial expansions". The desirability of the Yale graded
      introduction of one-pion exchange (OPE)-to-"searched" transition energies (E(tr))
      is brought out. Corrections for virtual discontinuities in phase-shift-energy
      dependence at the E(tr) decreased the violation of long-range charge independence
      (LRCI). The effect of two-pion exchange (TPE) has been calculated on the ps
      theory as approximately 1 for go(2)(p-p) - go(2)(n-p), go(2) = g(2)/[unk]c; a
      result consistent with LRCI. Searching all phase parameters including g(2) for
      both isospin values I in g(2) determinations from n-p data, but with fixed I = 1
      non-OPE phases as deduced from p-p data in the base search with frozen g(2), the
      OPE effect of the neutral pion, pi degrees , was separated from that of the
      charged pion, pi(c). The g(2) for pi(c) in n-p scattering is determined with much
      better statistical accuracy than that for pi degrees . The overall n-p value of
      g(2) is nearly equal to that for pi(c). The results suggest that the distinction
      between p-p and n-p values of g(2), if present, is in first approximation that
      arising from the difference between pi degrees -N and pi(c)-N couplings. Some
      limitations on the validity of the conclusions are mentioned.

PMID- 16591919
TI  - Model families of quadratic forms.
AB  - Let [unk] be the subinterval of R of values sigma </= gamma. Let there be given a
      family F of real valued symmetric quadratic forms [Formula: see text] in real
      variables z(1),...,z(mu). If for fixed sigma[unk][unk] a nonnull mu-tuple z is a
      critical point of Q(sigma), sigma will be called a characteristic root of F. When
      F satisfies Conditions I, II, and III below, the index of Q(sigma) is the "count"
      of characteristic roots of F less than sigma.

PMID- 16591920
TI  - Multipliers on compact lie groups.
AB  - Sufficient conditions are found for a biinvariant operator on a compact Lie group
      to be bounded on L(p), 1 < p < infinity. The proof uses properties of g-functions
      on such a group, and an analog to the familiar relationship between
      differentiation and multiplication under the Fourier transform.

PMID- 16591921
TI  - Experiments on osmosis with magnetic fluid.
AB  - Experiments on a ferromagnetic colloidal fluid at equilibrium showed equality
      between magnetic and osmotic force; this result identifies solute pressure
      against the free surface as the cause of the negative solvent pressure. Except
      for water of hydration, there is no other osmotic interaction between solute and
      solvent.

PMID- 16591922
TI  - The magnetic field induced by the bodily tide in the core of the Earth.
AB  - The motion in the liquid core of the earth due to the bodily tide can induce a
      periodic magnetic field having the frequency sigma of the tide as well as
      multiple frequencies, including a steady term. The coupling coefficient for the
      steady term between the convectively inducing and induced fields is estimated to
      be of the order of sigmaH(2)/lambda, where H denotes the height of the
      equilibrium tide, and lambda = 1/4pikappa, kappa denoting the electrical
      conductivity of the core. With sigma = 1.4 x 10(-4) sec(-1), H = 20 cm, and kappa
      = 3 x 10(-6) emu, the coupling coefficient comes out only of the order of 10(-6),
      as against unity in the case of the dynamo theory.

PMID- 16591923
TI  - Tricubic polynomial interpolation.
AB  - A new triangular "finite element" is described; it involves the 12-parameter
      family of all quartic polynomial functions that are "tricubic" in that their
      variation is cubic along any parallel to any side of the triangle. An
      interpolation scheme is described that approximates quite accurately any smooth
      function on any triangulated domain by a continuously differentiable function,
      tricubic on each triangular element.

PMID- 16591924
TI  - Induction of cytokinin-independent tobacco tissues by substituted fluorenes.
AB  - Two morphactins and three aminofluorenes initiated the formation of compact
      tissue nodules in hormone-dependent tobacco callus cultures. These nodules, upon
      subculture, behaved like partially transformed plant tumors. They grew on
      cytokinin-free media, while control callus and nonnodule tissue still required an
      exogenous cytokinin source. The data indicate that substituted fluorenes,
      including carcinogenic aminofluorenes, can cause a neoplastic growth response in
      cultured tobacco tissues. Of particular interest in this study is the finding
      that a directed and heritable cellular change is induced in tobacco tissue in
      which a specific (the endogenous cytokinin) biosynthetic system is regularly and
      persistently activated.

PMID- 16591925
TI  - The ages of the lunar seas.
AB  - Two ages are attributed to each circular lunar sea, the age of formation of the
      circular basin, probably by impact, and the age of the filling of the basin by
      lava-like effusions.Each lunar-sea surface displays a range of geomorphic
      indices. This is interpreted as being due to the presence of effusions of
      different ages on the surface of each sea. The landing sites of Apollo 11 and 12
      have geomorphic indices of value 10.3 and 8.4. The radiometric ages of the rocks
      are, respectively, approximately 3.65 x 10(9) and 3.36 x 10(9) years. The range
      of geomorphic indices on sea surfaces is from less than 5 to more than 14, which
      indicates that the two Apollo crafts landed on surfaces formed about in the
      middle of the total span of time of sea-surface formation. Using four possible
      relationships between geomorphic index and age, I conclude that the age of the
      youngest effusions is less than 3 x 10(9) years and the age of the oldest
      effusions is more than 4 x 10(9) years. The results of the analyses of the
      Russian Luna 16 samples, although preliminary, fit in this interpretation.

PMID- 16591926
TI  - A new labor theory of value for rational planning through use of the bourgeois
      profit rate.
AB  - To maximaze steady-state per capita consumptions, goods should be valued at their
      "synchronized labor requirement costs", which are shown to deviate from Marx's
      schemata of "values" but to coincide with bourgeois prices calculated at dated
      labor requirements, marked-up by compound interest, at a profit or interest rate
      equal to the system's rate of exponential growth. With capitalists saving all
      their incomes for future profits, workers get all there is to get. Departures
      from such an exogenous, or endogenous, golden-rule state are the rule in history
      rather than the exception. In the case of exponential labor-augmenting change, it
      is shown that competitive prices will equal historically embodied labor content.

PMID- 16591927
TI  - Conformation of cyclolinopeptide a observed by circular dichroism.
AB  - A stereochemical investigation, by circular dichroism, of a synthetic nonapeptide
      (cyclolinopeptide A) in several organic and organic-sulfuric acid solvents is
      presented. From this examination, and results found for a conformationally rigid
      model compound, 1,7,7-trimethyl-3-azabicyclo [2.2.1] heptan-2
      one(camphorolactam), it is concluded that cyclolinopeptide A may exist in several
      conformations in solution. None of these conformations is believed to be
      stabilized by intramolecular hydrogen bonds. Some details on an x-ray analysis of
      the cyclic nonapeptide are also presented.

PMID- 16591928
TI  - Conformation of cyclolinopeptide a observed by nuclear magnetic resonance
      spectroscopy.
AB  - The 220 MHz spectrum of the cyclic nonapeptide Phe-Phe-Leu-Ile-Ile-Leu-Val-Pro
      Pro (all L), designated cyclolinopeptide A, is analyzed by decoupling, exchange
      of peptide NH protons with deuterium, and measurement of the temperature
      dependence of the NH chemical shift. Measurement of the NH doublet spacings gives
      values of J(Nalpha), the vicinal coupling of alpha-CH and NH protons of specific
      amino acid residues. These in turn provide estimates of the rotation angles [unk]
      about the HN-C(alpha)H(alpha) bonds, which in combination with energy
      minimization studies, allow the determination of the conformation of the main
      chain. It is concluded that this polypeptide in dimethylsulfoxide solution does
      not contain intramolecular hydrogen bonds. Deuterium-exchange rates and
      temperature-dependence studies indicate that of the seven peptide NH protons,
      five are exposed to solvent, while two, which exchange somewhat more slowly than
      the others, may be situated in the interior of the ring.

PMID- 16591929
TI  - Approximate treatment of the conformational characteristics of a cyclic
      nonapeptide, cyclolinopeptide a.
AB  - Possible conformations for a cyclic nonapeptide that are consistent with
      conformation-dependent information obtained from an NMR investigation of the
      peptide in solution are presented. These several conformations are deduced from
      the myriad of possible conformations by eliminating from consideration all cyclic
      species having one or more residues in a conformation that does not correspond to
      the vicinal coupling constants observed by NMR between the amide and alpha
      protons. A Karplus-like relation connecting the dihedral angle [unk]' and the
      vicinal coupling J(Nalpha) between N-H and C(alpha)-H(alpha) is used to test this
      correspondence. A further reduction in the number of cyclic conformations under
      consideration is made possible by rejecting the conformations that have a high
      intramolecular conformational energy. The intramolecular conformational energy of
      the cyclic nonapeptide is estimated by summing the independent residue energies.
      These have been calculated by others with approximate potential functions to
      account for the intrinsic torsional potentials and the nonbonded steric (6-12
      potential) and electrostatic (monopole-monopole) interactions solely dependent
      upon one or both of the residue rotations, [unk] and Psi, about the N-C(alpha)
      and C(alpha)-C bonds, respectively.

PMID- 16591930
TI  - Beginnings of village-farming communities in southeastern Turkey.
AB  - Since the end of World War II, much evidence has accrued of the primary phase of
      village-farming community life in Southwestern Asia, which began about 7000 B.C.
      The remains of (usually) several of the positively domesticated animals (dog,
      sheep, goat, pig) and plants (wheat, barley, legumes such as peas and lentils)
      assure us that these settlements were based on effective food production,
      although collected wild foods also remained a significant portion of the human
      diet. Evidence of a transitional phase (or phases) that must have immediately
      preceded the primary phase of effective food production has, however, remained
      very elusive. Part of a breakthrough appears to have been made in the autumn 1970
      field campaign at Cayonu Tepesi in southeastern Turkey, where the expansion and
      deepening of earlier exposures has yielded evidence that may span a significant
      portion of the transition.

PMID- 16591931
TI  - Interactions in Colonies of Primitively Social Bees: Artificial Colonies of
      Lasioglossum zephyrum.
AB  - Lasioglossum zephyrum usually lives in small colonies but is facultatively
      solitary. Lone bees and colonies produced from female pupae of the same
      generation were established in artificial indoor nests. Both the length of the
      prereproductive period and the number of cells produced per bee per day decreased
      with increasing colony size. In most colonies, ovarially and behaviorally
      recognized castes arose, a queen and workers, but with all intergradations. The
      mean size of queens was larger than that of workers. Nearly all queens mated
      although few workers did so in rooms with a few males, but mating had no effect
      on subsequent behavior or ovarian development. In groups of diverse age there was
      a tendency for the oldest bees to be queens; queens also were larger on the
      average than workers. In groups of equal age, the largest bee was most often
      queen. As would be expected for a scarcely social species, mechanisms of social
      integration (resulting in division of labor and differentiation of castes) mostly
      appear to involve behavioral features of the solitary ancestors and accidental
      results of joint occupancy of nests. There is no evidence of direct food or
      pheromone transfer among adult bees.

PMID- 16591932
TI  - Regional Coexistence of Species and Competition between Rare Species.
AB  - A model is developed for the coexistence and exclusion of species over a region
      of similar habitable patches. Since the balance of local extinction and
      colonization would leave some patches unoccupied even without competitors,
      species may coexist even when all the patches are the same. Regional competition
      coefficients are found when species affect the local extinction or migration
      rates of each other. Rare species can regulate each other and even exclude other
      species completely.

PMID- 16591933
TI  - Interconnected patterns of biogeography and evolution.
AB  - Analysis of the fauna of the carabid beetles of New Guinea reveals both a broad
      dispersal pattern and a local turnover pattern that together fit into a world
      wide pattern of successive dispersals and replacements that run from large to
      small areas and from more to less favorable climates. This pattern coincides
      broadly with a world-wide pattern of species numbers. Evolution by group
      selection, proceeding most rapidly and effectively where species are most
      numerous, connects the patterns and can supply the force that gives direction to
      the dispersal pattern. Directional change at any level of complexity involves
      movement that results in the formation of diverse groups of units (which are
      themselves groups of smaller units) and differential survival. This process
      generalized group selection-has been continuous from chemical evolution on the
      earth's surface, through the origin of life, and into successive interacting
      levels of organic evolution. A corollary is that evolution should make situations
      favorable to itself, by group selection, and has probably done so in (for
      example) tropical rain forest, where new information about group evolution may be
      sought.

PMID- 16591934
TI  - Temperature Physiology of the Sea Snake Pelamis platurus: An Index of Its
      Colonization Potential in the Atlantic Ocean.
AB  - The yellow-bellied sea snake Pelamis platurus occurs throughout the tropical
      Indian and Pacific Oceans from east Africa to Central America. Its latitudinal
      distribution limits coincide with the 18 degrees C surface isotherm. P. platurus
      has upper and lower thermal tolerances of 36.0 and 11.7 degrees C. With rapid
      cooling, P. platurus stops feeding at 16-18 degrees C; however, it has a high
      resistance to cold temperature and can withstand 5 degrees C for 1 hr. After 10
      days' exposure, P. platurus does not acclimate to 17 degrees C and, thus, would
      not be able to survive for long periods in water this cold.In the event of its
      transit through the proposed Central American Sea-Level Canal, P. platurus would
      colonize the Atlantic Ocean and, during the summer months, would be able to
      extend its north Atlantic distribution to as far as Cape Cod and the English
      Channel.

PMID- 16591935
TI  - Stability of Plane Poiseuille Flow to Periodic Disturbances of Finite Amplitude,
      III.
AB  - The stability of plane Poiseuille flow to periodic disturbances of finite
      amplitude was reinvestigated by the use of 55 harmonics instead of five in the
      Orr-Sommerfeld expansion, but all the (20) overtones in each harmonic were
      dropped. The fundamental mode was chosen as the one of lowest phase velocity
      c(r), so as to enhance the wall effects. The neutral curve obtained gives values
      of the critical amplitude lambda(c) that are considerably higher than in the
      previous calculation. Near the critical Reynolds number, the neutral curve
      approaches the values derived previously by an analytical method.

PMID- 16591936
TI  - Effect of gravity on osmotic equilibria.
AB  - Experiments with colloidal suspensions of oil and iron oxide at equilibrium show
      that the buoyancy of the suspended particles is additive to the osmotic pressure
      and that the relation remains with the free surface and not with the membrane.
      The experiments contribute to the general concept that osmotic pressure is caused
      by the dispersal pressure of solute molecules and that the osmotic interaction
      with the water at equilibrium is due solely to a coupling at the free surface.

PMID- 16591937
TI  - Attenuation of seismic waves by grain boundary relaxation.
AB  - Experimental observations of the attenuation of elastic waves in polycrystalline
      ceramics and rocks reveal an attenuation mechanism, called grain boundary
      relaxation, which is likely to be predominant cause of seismic attenuation in the
      earth's mantle. For this mechanism, the internal friction (the reciprocal of the
      "intrinsic Q" of the material) depends strongly upon frequency and is in good
      agreement with Walsh's theory of attenuation (J. Geophys. Res., 74, 4333, 1969)
      in partially melted rock. When Walsh's theory is extended to provide a model of
      the anelasticity of the earth, using the experimental values of physical
      parameters reported here, the results are in excellent agreement with seismic
      observations.

PMID- 16591938
TI  - Natural Hybridization between the Cholla Cactus Species Opuntia spinosior and
      Opuntia versicolor.
AB  - The sexually reproducing cholla cactus species, Opuntia spinosior and O.
      versicolor, hybridize naturally in Arizona to produce hybrid swarms and
      segregating introgressive populations with a high degree of individual variation.
      The pattern of variation in these hybrid populations can be compared with that in
      populations derived from crossing of O. spinosior and O. fulgida, where the
      hybrids reproduce vegetatively rather than by seeds. The latter hybrid
      combination, in marked contrast to the former, results in clonal colonies with
      little or no observable individual variation.

PMID- 16591939
TI  - Tunnel model for hard-sphere bosons in their ground state.
AB  - In the tunnel model, a fluid is regarded as being composed of rows of molecules,
      which move almost in one dimension along lines or tunnels, the walls of which are
      formed by neighboring rows of molecules. This model provides a simple and
      reliable theory for a classical system of dense hard spheres. The tunnel model
      has also been applied to quantum hard spheres. However, until recently, there
      have been no reliable results for dense quantum hard spheres, so that the
      accuracy of the quantum tunnel model could not be judged. Comparison with a
      recent variational determination of the ground-state energy of a system of hard
      spheres shows that the tunnel model is reliable for this system.

PMID- 16591940
TI  - New Integral Representations for Solutions of Cauchy's Problem for Abstract
      Parabolic Equations.
AB  - A study has been made of Cauchy's problem for a class of abstract parabolic
      differential equations. Our study is based upon a transformation that maps
      solutions of second-order abstract Cauchy problems into solutions of first-order.
      This is a preliminary report on some of the results obtained. These results
      include (1) new representations for solutions of abstract parabolic equations,
      (2) applications to the heat equation, (3) a discussion of solution
      representations for second-order abstract Cauchy problems, and (4) applications
      to nonwell posed (in the sense of Hadamard) Cauchy problems.

PMID- 16591941
TI  - The spiral wave of our galaxy near inner lindblad resonance.
AB  - The dispersion relationship for short-wavelength spiral density waves in our
      Galaxy has been refined to remove the divergences that occurred in wave number
      and in amplitude as inner Lindblad resonance is approached. The wave is found to
      be evanescent in an annular region near 4 kpc. By 3 kpc, the inward propagating
      trailing wave is completely absorbed. The outgoing leading wave is suppressed
      compared to the trailing one because it begins in the evanescent state.
      Throughout this region of inner Lindblad resonance, a smooth wave amplitude has
      been obtained, and it has a sharp peak correlating well with the observed density
      of ionized hydrogen.

PMID- 16591942
TI  - Determination of distance distribution functions by singlet-singlet energy
      transfer.
AB  - The efficiency of energy transfer between two chromophores can be used to define
      an apparent donor-acceptor distance, which in flexible systems will depend on the
      R(0) of the chromophores. If efficiency is measured as a function of R(0), it
      will be possible to determine the actual distribution function of donor-acceptor
      distances. Numerical procedures are described for extracting this information
      from experimental data. They should be most useful for distribution functions
      with mean values from 20-30 A (2-3 nm). This technique should provide
      considerably more detailed information on end-to-end distributions of oligomers
      than has hitherto been available. It should also be useful for describing, in
      detail, conformational flexibility in other large molecules.

PMID- 16591943
TI  - Fluctuations in nonequilibrium systems.
AB  - The theory of fluctuations is extended to nonlinear systems far from equilibrium.
      Systems whose evolution involves two separate time scales, e.g., chemically
      reacting mixtures near a local equilibrium regime, are studied in detail. It is
      shown that the usual stochastic description of chemical kinetics based on a
      "birth and death" model is inadequate and has to be replaced by a more detailed
      phase-space description. This enables one to develop for such systems a plausible
      mechanism for the emergence of instabilities, in which the departure from the
      steady state is governed by large fluctuations of macroscopic size, while small
      thermal fluctuations are still described by a generalization of Einstein's
      equilibrium theory. On the other hand, far from a local equilibrium regime,
      infinitesimal fluctuations may increase and attain macroscopic values. In this
      case the system evolves to a state of "generalized turbulence", in which the
      distinction between macroscopic averages and fluctuations becomes meaningless.

PMID- 16591944
TI  - Theoretical analysis of emission spectra of electronic transitions of molecules
      in dense media.
AB  - The purpose of this paper is to investigate the nature of band shapes of emission
      spectra and their relation to the rate of nonradiative processes. Two cases are
      discussed, one in which the Franck-Condon principle applies and the other in
      which the electronic transition is symmetry-forbidden but vibronic-allowed. The
      moment relations of emission spectra have been derived and their applications
      demonstrated.The vibrational structuring in emission spectra is discussed and
      empirical equations for calculation of the shapes of vibrational bands are
      derived. It is found that from the shapes of vibrational bands one can obtain the
      information of intermolecular vibration and from the areas under vibrational
      bands one can determine the Franck-Condon factors of intramolecular vibration.

PMID- 16591945
TI  - The 24th mersenne prime.
AB  - The 24th Mersenne prime M(p) = 2(p) - 1, and currently the largest known prime,
      is 2(19937) - 1. Primality was shown by the Lucas-Lehmer test on an IBM 360/91
      computer. The 24th even perfect number is (2(19937) - 1).2(19936).

PMID- 16591946
TI  - Conformal solution theory: hard-sphere mixtures.
AB  - Conformal solution theory is examined. It is suggested that most difficulties
      associated with previous applications of this theory arise from the use of
      concentration-indepenent reference fluids. For the particular case of hard-sphere
      mixture, it is shown that if the reference fluid is chosen so as to make the
      first-order term in the theory vanish, good results are obtained.

PMID- 16591947
TI  - The Cochlea of the Dolphin, Tursiops truncatus: General Morphology.
AB  - The anatomy of the cochlea of the dolphin Tursiops truncatus was studied in a
      number of specimens after fixation by vital perfusion, cellodin embedding, and
      serial sectioning. The results reveal the general structural relations and
      cellular detail up to the limits of light microscopy. A description is given of
      the variations of structure along the course of the cochlea, in which there are
      many departures from the typical mammalian form, especially in the compact
      quality of the tissues and the sturdiness of its elements. Apparently these
      features represent an adaptation of the cetacean ear to the reception of high
      frequency sounds.

PMID- 16591948
TI  - Immunocytochemical localization of phytochrome.
AB  - An immunocytochemical assay, which localizes phytochrome in situ, indicates that
      this plant chromoprotein is associated with both nuclei and plastids, in addition
      to the cytoplasm. In an etiolated oat shoot, phytochrome is most abundant just
      behind the apex of the coleoptile, where it is associated with parenchyma cells;
      it is apparently absent at the extreme apx of the coleoptile. Further back from
      the tip, phytochrome is found in the epidermal cells of the coleoptile; it
      decreases in concentration toward the node, where it is again abundant.
      Phytochrome is also abundant in the extreme apical cells of young adventitious
      roots and in association with the procambium of the mesocotyl.

PMID- 16591949
TI  - The "fallacy" of maximizing the geometric mean in long sequences of investing or
      gambling.
AB  - Because the outcomes of repeated investments or gambles involve products of
      variables, authorities have repeatedly been tempted to the belief that, in a long
      sequence, maximization of the expected value of terminal utility can be achieved
      or well-approximated by a strategy of maximizing at each stage the geometric mean
      of outcome (or its equivalent, the expected value of the logarithm of principal
      plus return). The law of large numbers or of the central limit theorem as applied
      to the logs can validate the conclusion that a maximum-geometric-mean strategy
      does indeed make it "virtually certain" that, in a "long" sequence, one will end
      with a higher terminal wealth and utility. However, this does not imply the false
      corollary that the geometric-mean strategy is optimal for any finite number of
      periods, however long, or that it becomes asymptotically a good approximation. As
      a trivial counter-example, it is shown that for utility proportional to
      x(gamma)/gamma, whenever gamma not equal 0, the geometric strategy is suboptimal
      for all T and never a good approximation. For utility bounded above, as when
      gamma < 0, the same conclusion holds. If utility is bounded above and finite at
      zero wealth, no uniform strategy can be optimal, even though it can be that the
      best uniform strategy will be that of the maximum geometric mean. However,
      asymptotically the same level of utility can be reached by an infinity of nearby
      uniform strategies. The true optimum in the bounded case involves nonuniform
      strategies, usually being more risky than the geometric-mean maximizer's strategy
      at low wealths and less risky at high wealths. The novel criterion of maximizing
      the expected average compound return, which asymptotically leads to maximizing of
      geometric mean, is shown to be arbitrary.

PMID- 16591950
TI  - The Order of the Antipode of Finite-dimensional Hopf Algebra.
AB  - Examples of finite-dimensional Hopf algebras over a field, whose antipodes have
      arbitrary even orders >/=4 as mappings, are furnished. The dimension of the Hopf
      algebra is q(n+1), where the antipode has order 2q, q >/= 2, and n is an
      arbitrary positive integer. The algebras are not semisimple, and neither they nor
      their dual algebras are unimodular.

PMID- 16591951
TI  - Hypothetical explanations of the negative apparent effects of cloud seeding in
      the whitetop experiment.
AB  - In order to explain the apparent losses of rain ascribable to seeding at the
      Whitetop trial, particularly large and highly significant in the stratum E (but
      not in the opposite stratum W) of experimental days, it has been hypothesized
      that seeding causes widespread cloudiness and subsequent lowering of ground
      temperatures. This hypothesis is flatly contradicted by the observations: the
      seeded E-days (but not W-days) were uniformly less cloudy and hotter than those
      without seeding. Curiously, these differences prevailed not only from the
      scheduled time of seeding but also for several hours beforehand. The average
      rainfall for the 10 hr that preceded the time of seeding was investigated in
      eight "cells", defined by the day's wind direction to be downwind, upwind, and to
      the sides and "far" and "near" the center of seeding. Highly significant
      decreases were found in the far-upwind and far-left cells, indicating an
      earlymorning disparity between those E-days that later were declared as
      experimental to be seeded and those E-days that were declared as experimental not
      to be seeded. This disparity, difficult to explain by chance variation, suggests
      that particular caution be used in treating differences in the rainfall between
      seeded and not-seeded days in the Whitetop trial as having been caused by
      seeding.

PMID- 16591952
TI  - Hormonal Control of Lecithin Synthesis in Barley Aleurone Cells: Regulation of
      the CDP-Choline Pathway by Gibberellin.
AB  - The enzymes of the cytidine diphosphate-choline pathway, which is involved in
      lecithin biosynthesis, are present in imbibed barley aleurone cells. The first
      enzyme, choline kinase (EC 2.7.1.32), is found in the soluble protein fraction.
      Its activity is not affected by prior treatment of aleurone layers with
      gibberellin. The second and third enzymes of the pathway, phosphorylcholine
      cytidyl (EC 2.7.7.15) and phosphorylcholine-glyceride (EC 2.7.8.2) transferases,
      are associated with the particulate fractions. Their activities are greatly
      increased by gibberellin treatment during the lag phase (0-8 hr) of gibberellin
      effected alpha-amylase synthesis. The hormonal effects are evident two hours
      after gibberellin treatment. Inhibitors that block gibberellin-effected alpha
      amylase formation also inhibit the stimulation of these membrane-bound enzymes by
      the hormone.

PMID- 16591953
TI  - Synthesis and discharge of the coupling factor.adenosine diphosphate complex in
      spinach chloroplast lamellae.
AB  - The formation of a coupling factor.ADP complex is shown to be dependent on
      photoinduced electron transport, AMP, and P(i), and sensitive to arsenate and
      sulfate. The stability of the complex is unaffected by subsequent addition of
      arsenate, but is quite markedly sensitive to the addition of ADP. The data are
      discussed in relation to possible models of photophosphorylation, and in
      particular, to one in which coupling factor-bound, photosynthetically generated,
      ADP serves as a phosphoryl donor to substrate ADP.

PMID- 16591954
TI  - Comparison of faunal equilibrium turnover rates on a tropical island and a
      temperate island.
AB  - Rates of immigration and extinction of bird species on a tropical island, Karkar
      in the southwest Pacific Ocean, have been estimated from surveys made in 1914 and
      in 1969. Compared to a temperate-zone island of similar size and isolation (Santa
      Cruz off southern California), Karkar has a similar extinction rate, but a lower
      immigration rate expressed as a fraction of the mainland species pool, due to the
      sedentariness of many tropical forest birds. The probability of extinction is
      highest for species that are rare (due to narrow habitat requirements, large
      territory size, competition, recency of colonization, or marginal suitability of
      habitat), species with "in-and-out" tactics, and populations on small islands.

PMID- 16591955
TI  - Postulational basis of the law of increase of entropy.
AB  - The law increase of entropy is shown to be a consequence of the central
      assumption, in the manner of Gibbs, for the construction of the ensemble that
      represents the physical system. It is no longer necessary to make two separate
      assumptions in the Gibbs-Tolman development of the bases of statistical
      mechanics.

PMID- 16591956
TI  - Abstracts of papers presented at the autumn meeting of the national academy of
      sciences (USA), washington, d.C., 25-27 october 1971.

PMID- 16591957
TI  - A note on the ground state energy of an assembly of interacting electrons.
AB  - The ground state energy of an assembly of charged particles of density rho
      imbedded in a continuum of charge of the other sign in an electrically neutral
      system is considered. Asymptotic formulae for the ground state energy of such
      systems are known in the high- and low-density regimes. An interpolation formula
      covering the entire density range is derived using the method of two-point Pade
      approximants. A phase transition from an electron lettice to an electron gas
      seems to occur at r(3) congruent with 14, r(3) being the radius of a sphere
      which, on the average, contains a single charge, in units of the Bohr radius of
      the electron in a hydrogen atom.

PMID- 16591958
TI  - Van der waals interactions and exciton condensation.
AB  - It is shown that the van der Waals interaction can lead at low temperatures to a
      condensed state of excitons with properties in qualitative agreement with the
      observations of exciton droplets. Our calculation gives a binding energy of the
      correct sign and magnitude for the exciton condensate. In a diclectric medium,
      the strong enhancement of the exciton polarizability leads to a giant van der
      Waals interaction, and this interaction appears to make possible a condensed
      exciton phase.

PMID- 16591959
TI  - Evidence for hydrogen abstraction by classical radicals in the norbornenyl
      nortricyclyl system.
AB  - Studies of product compositions and deuterium-label rearrangements at various
      concentrations of tri-n-butyltin hydride in the reductions of exo-and endo-5
      bromonorbornene and 2-bromonortricyclcne to mixtures of norbornene and
      nortricyclene lead to three main conclusions: (i) at least two radical
      intermediates contribute to product formation; (ii) each intermediate yields
      predominantly (80% or more) one product; and (iii) nortricyclene is predominantly
      derived from a symmetrical intermediate. This constitutes strong evidence for
      hydrogen abstraction by classical (i.e., single-product) norbornenyl and
      nortricyclyl radicals. It is argued that the norbornenyl-nortricyclyl system is
      exceptionally well suited for the generation of a nonclassical (dual-product)
      radical; hence, the existence of a nonclassical radical in any other system is
      rather unlikely.

PMID- 16591960
TI  - Pyrolysis of organomercury compounds: investigation by the method of matrix
      isolation.
AB  - The method of matrix isolation has been used to investigate mechanisms of gas
      phase chemical reactions, in particular the pyrolysis of some organomercury
      compounds. A molecular beam of pyrolysis products was condensed simultaneously
      with a large excess of rare gas at temperatures from 5 to 15 degrees K to form a
      matrix that was subsequently studied by infrared spectroscopy. In the case of
      C(6)H(5)HgCCl(3), we found that pyrolysis in the temperature range 220-400
      degrees C produced mainly dichlorocarbene. In addition, some trichloromethyl
      radical was observed and increased in relative importance at increased
      temperatures. Another identified product of pyrolysis was C(6)H(5)HgCl. In
      general, the same reactive intermediates, CCl(2) and CCl(3), were found from
      pyrolysis of Hg(CCl(3))(2) in the temperature range 250-500 degrees C, along with
      CCl(3)HgCl and HgCl(2). The identity of CCl(2) and CCl(2) was demonstrated by
      measurement of the relative intensities and isotopic splittings of stretching
      vibrations due to the chlorine isotopes. Isotopic patterns found for CCl(2) are:
      v(3) (745.8, 744.0, 741.8 cm(-1)), v(1) (719.5, 717.0, 714.9 cm(-1)) and for
      CCl(3) are: v(3) (897.8, 896.4, 895.2, 893.9 cm(-1)). Less dilution with the rare
      gas or warming of the matrix produced a decrease of CCl(2) and CCl(3) spectral
      bands and an increase of bands due to C(2)Cl(4), C(2)Cl(6), and other products.
      These results show the usefulness of matrix isolation in the study of such
      reactive species as CCl(2) produced by pyrolysis in the gas phase.

PMID- 16591961
TI  - Harmonic Analysis and H-Functions on Siegel Domains of Type II.
AB  - It is known that the distinguished boundary of a Siegel domain of type II can be
      identified with a simply connected nilpotent Lie group of step two. The
      Plancherel formula for this group and the irreducible unitary representations
      which enter into that formula are determined. The H(2)-space of the domain and
      its Szego kernel are characterized in terms of the harmonic analysis of the above
      group, in particular, the integral representations for H(2)-functions due to
      Gindikin and Koranyi-Stein are shown to be instances of the Fourier inversion
      formula.

PMID- 16591962
TI  - Ramsey's Theorem for a Class of Categories.
AB  - Ramsey's Theorem states that for a sufficiently large set S, and for any
      splitting of the k-element subsets of S into r classes, there is a subset T [unk]
      S, [unk]T[unk] = l, such that all k-element subsets of T are in the same class.
      This paper establishes a theorem for certain categories that generalizes Ramsey's
      Theorem. In particular, it is strong enough to establish G-C. Rota's conjecture
      that the vector space analogue to Ramsey's Theorem is true. It also implies the
      Ramsey theorem for n-parameter sets, which has as corollaries, among others, the
      theorem of van der Waerden on arithmetic progressions and several results of R.
      Rado on regularity in systems of linear equations.

PMID- 16591963
TI  - Molecular orbital studies of ethylenediamine conformations.
AB  - Semiempirical quantum mechanical treatments are applied to the ethylenediamine di
      cation, mono-action, and neutral molecule by the use of the extended Huckel
      theory.The minimum energies of conformations of molecules for rotation about the
      CH(2)-CH(2) axis is found. The theoretical predictions for the conformation with
      minimum values. The importance of the ethylenediamine conformations are
      discussed.

PMID- 16591964
TI  - Preparation of amorphous solid water.
AB  - A method of preparation of solid amorphous water is reported, along with a
      demonstration of the absence of crystalline ice. The samples described are the
      first to be completely free of contamination with crystalline ice.

PMID- 16591965
TI  - Molecular buoyancy and osmotic equilibrium.
AB  - Measurements of osmotic equilibrium of colloidal solutions, ranging from 170,000
      to 20,000 in molecular weight, show that the negative buoyancy of the solute
      molecules is additive to the osmotic pressure. Seen together with earlier
      measurements of positive buoyancy of oil suspensions, these data confirm that the
      osmotic interaction between solute and solvent at equilibrium is purely a force
      coupling at the free surface.

PMID- 16591966
TI  - Airey's Converging Factor.
AB  - Asmptotic series for the calculation of functions, for values of the argument
      numerically >1, start off with terms whose numerical values decrease but, at a
      certain stage, the terms begin to increase in numerical value and must be
      ignored. At this stage, there may be two adjacent terms of equal numerical value;
      when the least term of the asymptotic series is spoken of, it is in reference to
      the first of these two terms. The sum of the initial terms of the asymptotic
      series up to, and including, the least term often furnishes a fair approximation
      to the desired value of the function being evaluated. It was early observed by
      computers that if the terms of the asymptotic series alternate in sign, this
      approximation was often improved by replacing the least term by its half. The
      factor by which the least term of the asymptotic series must be multiplied so
      that the true value of the function being evaluated is obtained by addition of
      this modified least term to the remaining initial terms of the asymptotic series
      is known as the converging factor for the asymptotic series. The converging
      factor for the asymptotic series involved in the calculation of the exponential
      integral, for large negative values of the argument, was given as a power series
      in the reciprocal of the argument by Airey; the first term of this series is
      (1/2). A method for the determination of the coefficients of this series is
      given.

PMID- 16591967
TI  - Holomorphic embedding of complex curves in spaces of constant holomorphic
      curvature.
AB  - A special case of Wirtinger's theorem asserts that a complex curve (two
      dimensional) holomorphically embedded in a Kaehler manifold is a minimal surface.
      The converse is not necessarily true. Guided by considerations from the theory of
      moduli of Riemann surfaces, we discover (among other results) sufficient
      topological and differential-geometric conditions for a minimal (Riemannian)
      immersion of a 2-manifold in complex projective space with the Fubini-Study
      metric to be holomorphic.

PMID- 16591968
TI  - Approximations to self-consistent field molecular wavefunctions.
AB  - Unparameterized and parameterized versions are outlined of a new method for
      approximating self-consistent field wavefunctions from first principles at the
      minimum basis set level for complex molecules containing hydrogen and first-row
      atoms. The Hartree-Fock self-consistent field equations for closed-shell
      molecules are solved, retaining all one-electron integrals, and approximating the
      two-electron Coulomb integrals, hybrid integrals, and exchange integrals of the
      form (i(A)j(A)[unk]i(A)j(A)) and (i(A)j(B)[unk]i(A)j(B)) for centers A and B. A
      symmetrically orthogonalized basis set is used and rotational invariance is
      achieved by transformation to local axes that are unique for atoms in anisotropic
      environments. Parameterization based upon first-principle self-consistent field
      wavefunctions for a large number of molecules yields F-matrix elements to 0.007
      atomic units (au), density matrix elements to 0.007 electrons, orbital
      populations and atomic charges to 0.01-0.02 electrons, orbital energies to 0.01
      au, and total energies to 0.02 au (all standard deviations), in computational
      times only a few times larger than those required for complete neglect of
      differential overlap calculations.

PMID- 16591969
TI  - Cochlear Structure in the Dolphin, Lagenorhynchus obliquidens.
AB  - The cochleas of five specimens of the Pacific white-sided dolphin, Lagenorhynchus
      obliquidens, that had been fixed by intravital perfusion, embedded in celloidin,
      and sectioned in a continuous series, were studied with particular attention to
      the numbers and distribution of hair cells and ganglion cells. The number of
      inner hair cells is estimated as 3272 and the number of outer hair cells is
      estimated as 12,899, for a total of 16,171 cells. The ganglion-cell population is
      estimated as 50,412 after correction for cell splitting in the sectioning
      process.

PMID- 16591970
TI  - Surface photometry of celestial sources from a space vehicle: introduction and
      observational procedures.
AB  - Diffuse celestial sources of relatively low surface brightness such as the Milky
      Way, zodiacal light, and gegenschein (or contre lumiere) can be studied most
      reliably from above the earth's atmosphere with equipment flown in artificial
      satellites. We review the techniques used and some of the difficulties
      encountered in day-time observations from satellites by the use of a special
      photometer and polarimeter flown in the orbiting skylab observatory, OSO-6.

PMID- 16591971
TI  - Ethylene: A Natural Regulator of Sex Expression of Cucumis melo L.
AB  - Sex expression in cucumber (Cucumis sativus L.) and muskmelon (C. melo L.) was
      correlated with endogenous ethylene production. Plants of gynoecious (all female)
      sex types of the two species produced more ethylene than monoecius (male-female)
      plants. C. melo plants of a gynoecious sex type that normally produce only
      pistillate (female) flowers, when grown with hypobaric ventilation to facilitate
      removal of endogenous gases by diffusion, produced perfect (hermaphroditic)
      flowers. When either the plant was returned to atmospheric pressure or when the
      reduced-pressure ventilating stream was supplemented with ethylene, the same
      plants produced pistillate flowers. Enrichment of the atmosphere at either normal
      or reduced pressure with CO(2), a competitive inhibitor of ethylene action, also
      resulted in development of perfect flowers. Foliar application of a
      benzothiadiazole, a postulated inhibitor of ethylene action, resulted in
      formation of perfect flowers on gynoecious plants of C. melo and of staminate
      (male) flowers on gynoecious C. sativus. Based on these findings, it is proposed
      that ethylene is an endogenous regulator of sex expression in C. sativus and C.
      melo.

PMID- 16591972
TI  - New Method to Prepare N-t-Butoxycarbonyl Derivatives and the Corresponding Sulfur
      Analogs from di-t-Butyl Dicarbonate or di-t-Butyl Dithiol Dicarbonates and Amino
      Acids.
AB  - Di-t-butyl dicarbonate and one of its dithiol analogs, practical methods of
      preparation for which are given, react with amino-acid esters to form the N-t
      butoxycarbonyl (t-BOC) derivatives and the thiol analogs in good yield under mild
      conditions. The thiol analogs are stable to acidic conditions, which rapidly
      remove the t-BOC group itself. t-Butyl trimethylsilyl carbonate forms a
      (CH(3))(3)Si ether from a N-thiol-t-BOC serine methyl ester. The N-thiol-t-BOC
      group can be removed from the -NHCOSR (R = t-butyl) by heating with peroxide
      acetic acid.Action of the dicarbonates described above has not been attended by
      racemization in the cases examined. The two dicarbonates may be useful as agents
      for selective blocking and deblocking of amino or other groups.

PMID- 16591973
TI  - Nonprotein amino acids from spark discharges and their comparison with the
      murchison meteorite amino acids.
AB  - All the nonprotein amino acids found in the Murchison meteorite are products of
      the action of electric discharge on a mixture of methane, nitrogen, and water
      with traces of ammonia. These amino acids include alpha-amino-n-butyric acid,
      alpha-aminoisobutyric acid, norvaline, isovaline, pipecolic acid, beta-alanine,
      beta-amino-n-butyric acid, beta-aminoisobutyric acid, gamma-aminobutyric acid,
      sarcosine, N-ethylglycine, and N-methylalanine. In addition, norleucine,
      alloisoleucine, N-propylglycine, N-isopropylglycine, N-methyl-beta-alanine, N
      ethyl-beta-alanine alpha,beta-diaminopropionic acid, isoserine, alpha,gamma
      diaminobutyric acid, and alpha-hydroxy-gamma-aminobutyric acid are produced by
      the electric discharge, but have not been found in the meteorite.

PMID- 16591974
TI  - A new proof of the interior gradient bound for the minimal surface equation in N
      dimensions.
AB  - An interior gradient bound for classical solutions of the minimal surface
      equation in n variables was established by Bombieri, De Giorgi, and Miranda in
      1968. We provide a new and simpler derivation of this estimate and partly develop
      in the process some new techniques applicable to the study of hypersurfaces in
      general.

PMID- 16591975
TI  - Conductance in Water-Poly(vinyl alcohol) Mixtures.
AB  - The conductance of 0.02-0.10 N potassium chloride in poly(vinyl alcohol)-water
      mixtures at 25 degrees decreases by about 50% as the polymer content increases
      from zero to 20% by weight, while the bulk viscosity increases from 0.0089 to
      over 1000 poises. Further increases in polymer concentration transform the highly
      viscous liquid into an elastomeric solid, in which the conductance still remains
      relatively high; it decreases significantly only after the glass composition (75%
      polymer at 25 degrees ) is reached. The internal viscosity, which controls ionic
      mobility, was estimated from the conductance data: it ranges from 0.01 to about
      0.14 over the range 0-55% polymer, similar to the viscosity of many ordinary
      liquids. Rates of diffusion-controlled processes involving small molecules in
      macromolecular media can, therefore, be expected to be similar to those in usual
      solution.

PMID- 16591976
TI  - A reassessment of the course of evolution of wheat.
AB  - Chromosome pairing in hybrids involving Triticum aestivum and new accessions of
      T. speltoides, and in an amphiploid of these species, indicates that T.
      speltoides can no longer be considered to be the donor of the B genome of the
      polyploid wheats. This necessitates a reconsideration of the genome relationships
      and evolutionary processes that gave rise to cultivated wheats.

PMID- 16591977
TI  - Optical versus thermal transitions in solids at high pressure.
AB  - Pressure-induced electronic transitions have been observed in a wide variety of
      materials. In particular, Mossbauer resonance studies under high pressure have
      revealed changes of oxidation state and spin state of iron as a function of
      pressure. These processes involve the thermal transfer of an electron to a new
      ground state of the system. The difference in energy between states is frequently
      measured by optical absorption. In this paper, we relate the energy of the
      optical absorption peak and its half-width to the difference in thermal energy
      between the two states as a function of pressure. We show that the optical peak
      will broaden with pressure only if there is a difference between the force
      constants of the ground and excited states. These relationships permit the
      prediction from optical absorption data of the pressure at which a new ground
      state will be obtained. We demonstrate that the predictions are qualitatively
      correct for the reduction of Fe(III) in a series of ferric hydroxamates, and for
      the low-spin to high-spin transition of Fe(II) in ferrous phenanthroline
      complexes.

PMID- 16591978
TI  - Formation of binaries from triple systems.
AB  - The dynamical behavior of three masses moving under their mutual gravitational
      attraction in a plane is investigated by a systematic series of numerical
      experiments. It is shown that in 73% of the cases, a triple system disintegrates
      in less than 150 time units (corresponding to about 150 crossing times), and a
      binary is formed with the third star that escapes at hyperbolic velocity. The
      average time for disintegration is of the order of 10(9) years for triple stellar
      systems, as well as for triple galaxies. The statistics of the escaping masses
      show that the escaping mass is usually, but not always, the smallest in the
      system. A simple equation, giving the balance between the negative energy stored
      in the binary and the positive energy necessary for escape, explains the results
      qualitatively.

PMID- 16591979
TI  - On zeta functions associated with prehomogeneous vector spaces.
AB  - In this note, we construct certain families of Dirichlet series that satisfy
      functional equations. We shall also indicate an arithmetical application of our
      results. The work presented here depends upon the theory of prehomogeneous vector
      spaces.

PMID- 16591980
TI  - Weak compactness and control measures in the space of unbounded measures.
AB  - We present a synthesis theorem for a family of locally equivalent measures
      defined on a ring of sets. This theorem is then used to exhibit a control measure
      for weakly compact sets of unbounded measures. In addition, the existence of a
      local control measure for locally strongly bounded vector measures is proved by
      means of the synthesis theorem.

PMID- 16591981
TI  - The size of localized States near the mobility edge.
AB  - The "mobility edge" is the critical point at which a transition from localized to
      extended character of the eigenfunctions occurs in the random lattice problem. We
      study the behavior of the eigenfunctions as this critical point is approached,
      and produce arguments that suggest that they fall off, on the average, as exp(
      alpha)R with range R, and that alpha alpha [E - E(c)](0.6).

PMID- 16591982
TI  - The [unk]-Neumann Problem on (Weakly) Pseudo-Convex Two-Dimensional Manifolds.
AB  - When the Levi-form vanishes at boundary points of a pseudo-convex manifold, more
      delicate invariants are required to describe the function theoretic properties of
      the manifold. These are introduced here; the proof of the main theorem and other
      results, which will be described in more detail elsewhere, are described.

PMID- 16591983
TI  - Significant structure theory of surface tension of the alkali metals.
AB  - The volume and temperature dependence of the solid-like structure in liquids has
      been properly taken into account in calculations of surface tension of the liquid
      alkali metals. The surface tension equation derived from the significant
      structure theory of liquids is used. The results are quite satisfactory when
      compared with observed values.

PMID- 16591984
TI  - Powers of representations of the rotation group (their symmetric, alternating,
      and other parts).
AB  - It has been known for more than three quarters of a century that the square of
      the irreducible representation D(j), of dimension 2j + 1, of the 3-dimensional
      rotation group R(3) contains the representations D(2j),D(2j - 1),...,D(1),D(0) of
      R(3), each occurring once. I give in this paper a method, involving no more than
      the expansion of (1 + x +... + x(2j))(n-1), of analyzing (D(j))(n), the nth power
      of D(j), n = 3, 4, 5,..., into the sum of the irreducible representations D(nj),
      D(nj - 1),..., D(1), D(0) of R(3), each occurring a stated number of times. When
      n = 2, the part D(2j) + D(2j - 2) +... + D(2) + D(0) of (D(j))(2) is associated
      with the partition (2) of 2 and is termed the symmetric part of (D(j))(2), while
      the remaining part, D(2j - 1) + D(2j - 3) +... + D(3) + D(1), of (D(j))(2) is
      associated with the partition (1(2)) of 2 and is termed the alternating part of
      (D(j))(2). For any value of n, (D(j))(n) contains various parts, each associated
      with a k-part partition of n, where k </= 2j + 1, the part associated with the l
      part partition (n) of n being termed the symmetric part of (D(j))(n) and the part
      associated with the n-part partition (1(n)) of n, where n </= 2j + 1, being
      termed the alternating part of (D(j))(n). If n > 2j + 1, (D(j))(n) has no
      alternating part. I show how to determine these various parts giving full details
      when j = 1 and n is arbitary, and when j is arbitrary and n = 3 or 4. I also show
      that when n = 2m + 1 is odd the alternating part of (D(j))(n) is, when it exists,
      i.e., when m </= j, the same as the symmetric part of (D(j - m))(n) and that the
      alternating part of (D(j))(n) is the same as the alternating part of (D(j))(n'),
      where n + n' = 2j + 1. This implies that, when n is even and <2j + 1, the
      alternating part of (D(j))(n) is the same as the symmetric part of (D(n/2))(2j+1
      n).

PMID- 16591985
TI  - A class of bounded pseudo-differential operators.
AB  - Pseudo-differential operators of order -M and type rho, delta(1), delta(2) are
      shown to be bounded in L(2) provided that 0 </= rho </= delta(1) < 1, 0 </= rho
      </= delta(2) < 1, and [Formula: see text].

PMID- 16591986
TI  - Molecular complexes of methoxyindoles with 1,3,5-trinitrobenzene and
      tetracyanoethylene.
AB  - Association constants for 1:1 molecular complexes formed between 1,3,5
      trinitrobenzene and various methoxy-substituted indoles have been determined by
      chemical-shift measurements in their nuclear magnetic resonance spectra. The
      values of association constants for the molecular complexes are comparable to
      those obtained by optical spectroscopy. The effect on the association constants
      and relative chemical shifts of the acceptor protons of the pure complexes of
      various donors is considered. The association constants and relative chemical
      shifts of the complexes determined by different protons on the nidoles in the
      presence of an excess of 1,3,5-trinitrobenzene are different. The possible
      structure of the complexes is discussed. The molecular complexes between
      tetracyanoethylene and various methoxyindoles have also been studied.

PMID- 16591987
TI  - Proof that unsuccessful speculators confer less benefit to society than their
      losses.
AB  - It is well known that successful speculation can be a boon to society, whether or
      not the successful speculator is ruled to be the legitimate appropriator of his
      profits. It is also understood that unsuccessful speculation can naturally impose
      losses on the unsuccessful speculator himself. Little, however, is known about
      the effect of the unsuccessful speculator on the rest of society: one view is
      that the others gain what he loses, so that in a sense he is their benefactor and
      only his own enemy; a more plausible view is that his loss must in some sense
      exceed the gain splashed on others. Nothing seems to have been proved in a
      rigorous way in this matter.Here, the problem is subjected to mathematical
      analysis. It is shown that others do definitely gain from an act of unsuccessful
      speculation, thus providing rigorous proof of what has long been surmised. But it
      is also shown that their gain is necessarily less, in an objective sense, than
      the loss to the speculator himself. Indeed, in the model of unnecessary positive
      carryover of grain into the future, the gain to the nonspeculators is proved to
      be actually of a second-order of smallness of infinitesimals compared to the
      speculator's loss.

PMID- 16591988
TI  - A limit theorem on the cores of large standard exchange economies.
AB  - This note introduces a new mathematical tool, nonstandard analysis, for the
      analysis of an important class of problems in mathematical economics-the relation
      between bargaining and the competitive price system.

PMID- 16591989
TI  - Pseudo-Poles in the Theory of Emden's Equation.
AB  - It is known that Emden's equation y'' = x(1-m)y(m) has movable singularities
      where the solution becomes infinite for one-sided approach. If m = (p + 2)/p, p
      positive integer, the singularities look like poles of order p. In this note
      expansions in terms of powers and logarithms are obtained from which the nonpolar
      nature of these "pseudo-poles" becomes evident. Various extensions are
      considered. Convergence proofs are deferred to a more detailed publication.

PMID- 16591990
TI  - Significant liquid-structure theory of viscosity and self-diffusion of the alkali
      metals.
AB  - Significant liquid-structure theory has been used to calculate the transport
      properties of the alkali metals. Unlike previous calculations, the volume and
      temperature dependence of the solid-like structure has been taken into
      consideration. Equations for the potential energy as a function of volume of the
      alkali metals, which lead to agreement between calculated and experimental values
      of thermodynamic and transport properties, are given. The calculated results are
      in satisfactory agreement with the experimental data.

PMID- 16591991
TI  - Re-evaluation of the Arizona cloud-seeding experiment.
AB  - The apparent effect of cloud seeding on the average 24-hr precipitation in the
      Santa Catalina Mountains during the two programs of the 7-year-long Arizona
      experiment was found to be a 30% loss of rain (P = 0.06). Considering rainy days
      only, the apparent effect is a 34% loss of rain (P = 0.03). On South-East days
      the apparent loss was 40% (P = 0.03). The analysis of the diurnal variation in
      the amounts of hourly precipitation brought out two suggestions: (i) more active
      silver iodide enters the clouds through seeding at their bases than at the -6
      degrees C level; (ii) the population of experimental days includes two categories
      with opposite responses to seeding: augmentations of rain in one case and losses
      in the other. These suggestions require independent confirmation.

PMID- 16591992
TI  - Pollen feeding and reproductive biology of heliconius butterflies.
AB  - Butterflies of the neotropical Genus Heliconius feed on pollen. This is the first
      known instance in butterflies of a habit that is well known for other insects.
      The butterflies remove amino acids and proteins from pollen; this feeding
      innovation plays a role in the reproductive and population biology of these
      insects. It is suggested that other animals may use pollen in a similar fashion.

PMID- 16591993
TI  - A new characterization of quasi-analytic classes of C-functions.
AB  - It is shown that a basic class C{M(n)} of C(infinity)-functions contains only
      quasi-analytic functions if, and only if, every function in C{M(n)} maps Borel
      sets onto Borel sets.

PMID- 16591994
TI  - Dissipative properties of quantum systems.
AB  - We consider the dissipative properties of large quantum systems from the point of
      view of kinetic theory. The existence of a nontrivial collision operator imposes
      restrictions on the possible collisional invariants of the system. We consider a
      model in which a discrete level is coupled to a set of quantum states and which,
      in the limit of a large "volume," becomes the Friedrichs model. Because of its
      simplicity this model allows a direct calculation of the collision operator as
      well as of related operators and the constants of the motion. For a degenerate
      spectrum the calculations become more involved but the conclusions remain simple.
      The special role played by the invariants that are functions of the Hamiltonion
      is shown to be a direct consequence of the existence of a nonvanishing collision
      operator. For a class of observables we obtain ergodic behavior, and this
      reformulation of the ergodic problem may be used in statistical mechanics to
      study the ergodicity of large quantum systems containing a small physical
      parameter such as the coupling constant or the concentration.

PMID- 16591995
TI  - omega-Theorems for Riemann's Zeta-Function at Harmonic Combinations of Points.
AB  - For integer r >/= 2 there are arbitrarily large T for which [Formula: see text]
      With s = sigma + it, corresponding results hold for sigma = c, 1/2 </= c < 1, and
      for 1/zeta(1 + it). A similar result holds for [Formula: see text].

PMID- 16591996
TI  - Physical adsorption of the quantum gas.
AB  - The significant structure theory of quantum liquids such as hydrogen, deuterium,
      and helium has been applied to the physical adsorption occurring in the
      submonolayer region. The partition function for the two-dimensional adsorbed
      fluid has been derived. The properties of isothermal and isosteric heat show good
      agreement with the available data from the literature.

PMID- 16591997
TI  - Bifurcation theory and the type numbers of marston morse.
AB  - Let H be a real Hilbert space and f(x,lambda) be a C(2) operator mapping a small
      neighborhood U of (x(0),lambda(0)) epsilon (H x R(1)) into itself. We investigate
      the solutions of the equation f(x,lambda) = 0 near a solution (x(0),lambda(0)),
      assuming that f(x,lambda) is a gradient mapping and 0 < dim Ker
      f(x)(x(0),lambda(0)) < infinity. In particular, we show that the type numbers of
      Marston Morse for an isolated critical point can be used to prove the existence
      of a point of bifurcation at (x(0),lambda(0)). An application of this result is
      given to the discovery of periodic motions near a stationary point for a large
      class of nonlinear Hamiltonian systems in "resonant" cases.

PMID- 16591998
TI  - Experimental evidence of an x-ray laser.
AB  - A three-stage neodymium:glass laser has been used to produce collimated x
      radiation from an aqueous copper(II) sulfate gel. The 1.06-mum Q-switch pulse
      from the neodymium laser was focused by a cylindrical lens to a horizontal line
      traversing a microscope slide sandwich that contained a thin film of gel. The
      emission from the gel was detected as a 0.2-mm spot on shielded, standard x-ray
      photographic film at distances that varied from 30 to 110 cm from the sandwich.
      Spot size did not increase with distance, suggesting coherence of the x-rays.

PMID- 16591999
TI  - Patterns of Genetic Differentiation in the Slender Wild Oat Species Avena
      barbata.
AB  - Allozyme frequencies at five enzyme loci were determined for 14 California
      populations of Avena barbata, a species introduced to California from the
      Mediterranean Basin during the colonization of North America. Allelic frequencies
      at these loci were also determined in Mediterranean collections of this species.
      The pattern of divergence of the California populations from the ancestral gene
      pool was not random and was strongly correlated with environment; thus, the
      pattern is not in accord with the hypothesis that most electrophoretically
      detectable variants are adaptively neutral. Rates of gene substitution in
      California were also not in accord with the neutrality hypothesis. The
      observations are, however, compatible with predictions of Neo-Darwinian
      evolutionary theory. We interpret these observations to indicate that natural
      selection plays a major role in determining the unique patterns of distribution
      of genetic variability in the slender wild oat in California.

PMID- 16592000
TI  - Magnetic circular dichroism of molecules in dense media: benzene.
AB  - This paper presents some calculated results on the vibrational structuring of the
      magnetic circular dichroism of the benzene (1)A(1g)"(1)B(2u) transition. The good
      agreement between the experimental and calculated relative intensities of the B
      bands (positive magnetic circular dichroism bands) indicates that these bands are
      mainly induced by the e(2g) 1596 cm(-1) mode. The unfavorable results obtained by
      comparison of the theoretical results with experimental results for the A-bands
      (negative magnetic circular dichroism bands) is presumably due to neglect of the
      contribution from the e(2g) 3056 cm(-1) mode, from hot bands, and from the
      transitions of normal modes other than the A(1g) 992 cm(-1) mode. It should be
      noticed that while the e(2g) 608 cm(-1) mode plays a dominating role in the
      ultraviolet spectrum of benzene, in the magnetic circular dichroism of benzene,
      the e(2g) 1596 cm(-1) mode is, if not more important, at least as important as
      the e(2g) 608 cm(-1) mode.

PMID- 16592001
TI  - In Vitro Photoreactions of Chlorophyll and Photosynthetic Energy Conversion:
      Chlorophyll-Quinone-Ethanol at Low Temperature as an Analog of Photosystems I and
      II.
AB  - Illumination at low temperatures of ethanol solutions of p-benzoquinone, alone or
      in the presence of chlorophyll or pheophytin, leads to the reversible formation
      of radical complexes. Based on g-value determinations and deuterium-substitution
      effects, the radicals are identified as a semiquinone and an ethoxy radical. In
      the porphyrin-sensitized system, ternary complexes are produced. Chlorophyll also
      forms a cation radical upon illumination, whereas pheophytin does not. The
      generation of this cation radical is independent of the presence of quinone, and
      proceeds via the chlorophyll singlet state, as opposed to quinone and ethoxy
      radical production, which involve triplet states. The significance of these
      reactions to photosynthetic energy conversion is discussed.

PMID- 16592002
TI  - Microgeographical Variation in Allozyme Frequencies in Avena barbata.
AB  - Microgeographical distribution of alleles of five enzyme loci and one
      morphological variant has been determined within populations of A. barbata
      occupying sites that are transitional between different vegetational zones. The
      results show that the spatial distribution of alleles is nonrandom and highly
      correlated with habitat in patterns that parallel the distribution of the same
      alleles in major climatic zones in California. It is concluded that the observed
      patterns of variation are best explained by Neo-Darwinian evolutionary models, in
      which selection plays a predominant role.

PMID- 16592003
TI  - Phytochrome and photosystem I interaction in a high-energy photoresponse.
AB  - AT LEAST TWO PHOTOREACTIONS CAN BE DEMONSTRATED IN PLANT DEVELOPMENTAL RESPONSES:
      the low-energy requiring phytochrome system and the high energy reaction. The
      action of these photoreactions on the formation of anthocyanin by turnip
      seedlings is discussed. The synthesis of small amounts of anthocyanin can be
      controlled solely by phytochrome, as evidenced by the red-far-red photoreversible
      effect of brief irradiations. Appreciable synthesis requires prolonged
      irradiations, the duration of irradiation being more important than intensity.
      The data presented suggest that the energy dependence of anthocyanin synthesis
      arises through photosynthesis. A mechanism for the interaction between
      photosynthesis and phytochrome is suggested. Under conditions of natural
      illumination of plants, the concentration of the species of phytochrome that
      absorbs far-red light may be lower than previously realized.

PMID- 16592004
TI  - Catalytic accelerations of 10-fold by an enzyme-like synthetic polymer.
AB  - A synthetic polymer, polyethyleneimine containing dodecyl (C(12)H(25))-chains for
      binding sites and imidazole moieties for functional catalytic groups, catalyzes
      the hydrolysis of phenolic sulfate esters by a two-step mechanism resembling that
      of the corresponding natural enzyme. Quantitative rate studies give kinetic
      parameters that show that the polymer (synzyme) accelerates the rate 10(12)-fold
      compared to unbound imidazole, and 10(2)-fold compared to a type IIA aryl
      sulfatase enzyme.

PMID- 16592005
TI  - Sensitivity of the contact chemoreceptors of the blowfly to vapors.
AB  - Contact chemoreceptors on the mouthparts and legs of the blowfly Phormia regina
      that normally respond to aqueous solutions of sapid substances also respond to
      compounds in the gaseous state. Effective vapors include organic and inorganic
      acids and various unrelated nonpolar compounds. In general, the acids stimulate
      the salt receptor. Some nonpolar compounds stimulate the salt receptor while
      others inhibit it. Others stimulate the water, sugar, or "fifth" receptor.
      Differential action cannot be attributed to pH or solubility. Not all compounds
      that are irritating to mammalian mucous membranes or amphibian skin stimulate the
      contact chemoreceptors of the fly. Sensitivity to these vapors is a phenomenon
      analogous to the common chemical sense of vertebrates.

PMID- 16592006
TI  - Entanglement coupling in linear polymers demonstrated by networks crosslinked in
      States of strain.
AB  - Linear 1,2-polybutadiene is crosslinked at 0 degrees by gamma-irradiation while
      strained in simple extension, with extension ratios from 1.3 to 2.0. During
      irradiation times up to several hours, entanglement slippage is slight, since the
      temperature is only slightly above the glass transition. Subsequently, samples
      are released and reach their equilibrium states of ease at room temperature. From
      the extension ratio at state of ease, the ratio of nu(x) (effective network
      strands terminated by crosslinks introduced) to nu(N) (effective network strands
      terminated by entanglements) is calculated by composite network theories of Flory
      and others; and from the extension ratios together with the modulus, measured at
      small extensions, nu(N) is calculated explicitly. It appears that nu(x) increases
      approximately proportional to irradiation time; nu(N) is approximately
      independent of irradiation, and it corresponds to a molecular weight between
      effective entanglement loci of about 13,000. This figure, however, which is
      larger than that deduced from rheological properties of the uncrosslinked
      polymer, is subject to future downward correction for partial entrapment of the
      entanglements and other refinements.

PMID- 16592007
TI  - Somatic mutational transients: models of response to acute and distributed doses
      of radiation applied to growing plants.
AB  - After limited exposures of whole plants to gamma radiation, the induced-mutation
      frequency, measured in somatic tissue of successively blooming flowers, is a
      transient function of time. Quantitative interpretation of the data is aided by
      construction of a cell-generation model. Seven theoretical models are designed to
      represent interaction between the cell-generation model and seven different modes
      of application of the radiation treatment. The models provide a structure for
      integration of the mutational contributions from different floral primordia.
      These different contributions are distributed over the array of mature flowers by
      the quantitative relationships of each model. A mathematical expression for the
      average response of a model can be equated to the average observed response and
      solved for the implied mutation rate per cell per roentgen.

PMID- 16592008
TI  - Evaluation of the distribution of distances between energy donors and acceptors
      by fluorescence decay.
AB  - When transfer of electronic excitation energy occurs between a donor-acceptor
      pair by the Forster mechanism, the decay of fluorescence of the donor follows
      first-order kinetics, with a rate constant that depends on the distance from
      donor to acceptor. In a system that contains donor-acceptor pairs of different
      separations, the fluorescence decay of the donors will not be exponential, but
      will depend on the distribution function of donor-acceptor distances, f(r).
      Various approaches are outlined for the extraction of information about f(r) from
      the decay curve of donor fluorescence. Specifically, if a plausible expression
      with adjustable parameters is assumed for f(r), numerical methods can be used to
      evaluate the parameters that yield the closest fit between the observed decay
      curve and that calculated from the assumed f(r). The technique of fluorescence
      decay may prove to be useful for determination of distribution functions of end
      to-end distances of polymers to the edges of which suitable donor-acceptor
      chromophore pairs have been attached.

PMID- 16592009
TI  - Parasexual interspecific plant hybridization.
AB  - Interspecific plant hybrids have been produced by parasexual procedures.
      Protoplasts of Nicotiana glauca and N. langsdorffii were isolated, fused, and
      induced to regenerate into plants. The somatic hybrids were recovered from a
      mixed population of parental and fused protoplasts by a selective screening
      method that relies on differential growth of the hybrid on defined culture media.
      The biochemical and morphological characteristics of the somatically produced
      hybrid were identical to those of the sexually produced amphiploid.

PMID- 16592010
TI  - Stationary spherical vortices in a perfect fluid.
AB  - Necessary conditions are derived for a spherical vortex in a perfect fluid to be
      stationary in the case when the velocities depend on a single surface harmonic.
      The motion is indeterminate unless an additional condition is imposed. In the
      case when this condition is incompressibility, the equations are solved, yielding
      a class of stationary spherical vortices.

PMID- 16592011
TI  - omega-Theorems for Quotients of Zeta-Functions at Combinations of Points.
AB  - Theorem A. Let q >/= O and r >/= O be integers. Let s = sigma + it, let zeta(s)
      be the Riemann zeta-function, let G(o)(s) = 1, and [Formula: see text] and let
      F(s) = G(q)(s)/H(r)(s). Then as t --> infinity lim sup [unk]F(1 + it)[unk]/(log
      log t)(q+r+1) >/= (6/pi)(2))(r+1) exp {(q + r + 1)gamma}, where gamma is Euler's
      constant.Stronger results such as proved in [1] are valid, and in particular q
      and r can be allowed to increase with t as in [1]. Results involving the real
      part of the sum of the factors of G(q) and of the reciprocals of the factors of
      H(r) can be proved much as in [3].

PMID- 16592012
TI  - Parallel subtraction of matrices.
AB  - A new Hermitian semidefinite matrix operation is studied. This operation-called
      parallel subtraction-is developed from the theory of parallel addition. Since the
      theory of parallel addition is motivated by the analysis of interconnected
      electrical networks, parallel subraction may be interpreted in terms of the
      synthesis of electrical networks. The idea of subtraction is also extended to
      hybrid addition.

PMID- 16592013
TI  - On coupled rate equations with quadratic nonlinearities.
AB  - Rate equations with quadratic nonlinearities appear in many fields, such as
      chemical kinetics, population dynamics, transport theory, hydrodynamics, etc.
      Such equations, which may arise from basic principles or which may be
      phenomenological, are generally solved by linearization and application of
      perturbation theory. Here, a somewhat different strategy is emphasized.
      Alternative nonlinear models that can be solved exactly and whose solutions have
      the qualitative character expected from the original equations are first searched
      for. Then, the original equations are treated as perturbations of those of the
      solvable model. Hence, the function of the perturbation theory is to improve
      numerical accuracy of solutions, rather than to furnish the basic qualitative
      behavior of the solutions of the equations.

PMID- 16592014
TI  - Cohomology of various completions of quasicoherent sheaves on affines.
AB  - Let O be a complete discrete valuation ring and let A be a commutative O-algebra.
      Let M be any A-module. In this paper, a class of completions M on the affine X
      corresponding to A, which includes, e.g., the Washnitzer-Monsky completion [1],
      and the full completion is studied. We then prove that for all of these
      completions we have, H(i)(X,M(+)) = O for i >/= 1, H degrees (X,M(+)) = M(+).

PMID- 16592015
TI  - Unification theorem for the two basic dualities of homothetic demand theory.
AB  - When income elasticities of demand are all unity, every dollar being spent in the
      same proportions at all levels of income, a homogeneous-first-degree, concave
      utility function exists to serve as an unequivocal measure of real output. Dual
      to it, and with identical concavity and homogeneity properties, is the minimized
      cost-per-unit-of-output, a function of prices. Distinct from this production dual
      is the indirect-utility dual, representing, except for algebraic sign, the
      maximized level of utility attainable as a function of prices relative to income.
      These basic alternative dualities are shown to be related by a unifying theorem:
      The logarithm of either of the pair of production-dual functions has for its
      indirect-utility dual the logarithm of the other function. What is shown to be
      the same thing, the indirect-utility dual of the output function is, except for
      sign, the reciprocal of the output's production-dual.

PMID- 16592016
TI  - Conformally flat manifolds.
AB  - This note describes some new examples of conformally flat manifolds, as a step
      toward a classification of such manifolds up to conformal equivalence.

PMID- 16592017
TI  - Group selection on the boundary of a stable population.
AB  - A model of group selection is constructed for the case of differential extinction
      acting on small boundary populations of a large, fixed population. Consideration
      is restricted to extinction operators acting at or near to carrying capacity.
      Under the assumption that the extinction rate is large relative to individual
      genetic parameters affecting gene frequencies in boundary populations, we discuss
      the conditions under which differential extinction is most likely to produce a
      significant effect. In particular, a condition for bimodality in the distribution
      of gene frequencies in boundary populations (population polymorphism) is that
      there be some critical allele frequency at which the extinction rate jumps from
      high to low. An extinction operator linear in allele frequency produces no
      qualitative effect of this kind. In consequence, we are able to make precise
      rather limited circumstances under which group selection is likely to have a
      significant effect.

PMID- 16592018
TI  - Stochastic Model of Unimolecular Reactions and the RRKM Theory.
AB  - A stochastic model of unimolecular reactions has been adopted for investigation
      of the validity and limitation of the RRKM theory. The error caused by the steady
      state approximation for distribution of energized molecules is small, while the
      assumption of the internal energy equilibration of energized molecules might
      cause serious errors for reactions of low activation energies.

PMID- 16592019
TI  - Distribution function inequalities for singular integrals.
AB  - This paper describes some distribution function inequalities between maximal
      functions and singular integral operators.

PMID- 16592020
TI  - Computation of large molecules with the hartree-fock model.
AB  - The usual way to compute Hartree-Fock type functions for molecules is by an
      expansion of the one-electron functions (molecular orbitals) in a linear
      combination of analytical functions (LCAO-MO-SCF, linear combination of atomic
      orbitals-Molecular Orbital-Self Consistent field). The expansion coefficients are
      obtained variationally. This technique requires the computation of several
      multicenter two-electron integrals (representing the electron-electron
      interaction) proportional to the fourth power of the basis set size. There are
      several types of basis sets; the Gaussian type introduced by S. F. Boys is used
      herein. Since it requires from a minimum of 10 (or 15) Gaussian-type functions to
      about 25 (or 30) Gaussian functions to describe a second-row atom in a molecule,
      the fourth power dependency of the basis set has been the de facto bottleneck of
      quantum chemical computations in the last decade.In this paper, the concept is
      introduced of a "dynamical" basis set, which allows for drastic computational
      simplifications while retaining full numerical accuracy. Examples are given that
      show that computational saving in computer time of more than a factor of one
      hundred is achieved and that large basis sets (up to the order of several hundred
      Gaussian functions per molecule) can be used routinely.It is noted that the
      limitation in the Hartree-Fock energy (correlation energy error) can be easily
      computed by use of a statistical model introduced by Wigner for solid-state
      systems in 1934.Thus, large molecules can now be simulated by computational
      techniques without reverting to semi-empirical parameterization and without
      requiring enormous computational time and storage.

PMID- 16592021
TI  - Note on the convergence of sequences of rational functions of best approximation
      to a meromorphic function.
AB  - If the function f(z) is meromorphic at every finite point of the plane, analytic
      on C: [unk]z[unk] </= 1, there are results that can be established concerning the
      convergence of the sequence R(n)(z) of rational functions of each degree n of
      best approximation to f(z) on C. However, we need to assume certain additional
      conditions on the convergence of the sequence R(n)(z) itself. The results
      generalize to more general sets C and to more general functions.

PMID- 16592022
TI  - A manner of characterizing the development of countries.
AB  - An attempt is made to characterize the socio-economic state and the temporal
      evolution of countries by the use of labor force distribution data on a
      multidimensional phase plot so that the development of a country is represented
      by an evolutionary track of a phase point. The evolutionary tracks of several
      countries are examined, and the phase points of many countries are compared.
      Snowflake diagrams, which make easy comparison of the socio-economic character of
      various countries, have also been developed.

PMID- 16592023
TI  - Quantum statistical theory of rate processes.
AB  - A general quantum mechanical approach for treating a great number of rate
      processes is developed and the temperature dependence of the rate constants is
      discussed.

PMID- 16592024
TI  - Biogeographic kinetics: estimation of relaxation times for avifaunas of southwest
      pacific islands.
AB  - When species diversity S on an island is displaced from the equilibrium value by
      injection or removal of species, S relaxes to equilibrium by an imbalance between
      immigration and extinction rates. Estimates of exponential relaxation times,
      t(r), for avifaunas of New Guinea satellite islands are calculated from analysis
      of four "experiments of nature": recolonization of exploded volcanoes,
      contraction in island area due to rising sea level, severing of land bridges, and
      disappearance of landbridge relict species. t(r) is in the range 3,000-18,000
      years for avifaunas of islands of 50-3000 square miles (130-7800 km(2)), and
      increases with island area. Immigration coefficients decrease and extinction
      coefficients increase with increasing S. The results may be relevant to the
      design of rainforest preserves.

PMID- 16592025
TI  - Thermal effect in opal below room temperature.
AB  - Opal, once believed to be amorphous silica, was shown by Levin and Ott (1932, J.
      Amer. Chem. Soc. 54, 828-829) to give an x-ray powder pattern of the high
      temperature form of cristobalite. The early explanation of this anomalous
      existence of a phase below its high-low transition temperature is now known to be
      untenable. One of us suggested that the tiny sizes of the component cristobalite
      crystals might explain the anomaly; if so, the transition might be expected below
      ambient temperatures. The record of a du Pont 900 Thermoanalyzer indeed revealed
      heat effects in opal below ambient temperatures, with an exotherm having a
      maximum at about -40 degrees on cooling and an endotherm that began about -50
      degrees on heating. This was not a latent-heat effect due to the high-low
      transition of cristobalite, however, for the low-cristobalite pattern persisted
      to below -50 degrees . Opal normally contains 4-9% water, which is tenaciously
      held; water loss is nearly linear with temperatures up to about 422 degrees ,
      when water loss is abruptly complete. Water-free opal does not display the
      thermal effect, but the same opal rehydrated does display it. Water is housed in
      minute voids, judged to be a few hundred Angstroms across, between minute
      particles of cristobalite. This water behaves differently from water in bulk, for
      its begins to melt at about -50 degrees .

PMID- 16592026
TI  - One-parameter equation of state for metals and certain other solids.
AB  - A GENERAL ISOTHERMAL EQUATION OF STATE FOR METALS AND CERTAIN OTHER SOLIDS
      [FORMULA: see text] Where BT(0) is the bulk modulus at zero pressure, P is the
      pressure, and V(0) and V are the volumes at zero pressure and pressure P,
      respectively, has been discovered empirically. The fit to a straight line for
      twenty metals and twelve metallic halides is within a few percent mean deviation.
      The rationale leading to this particular relation is that of the Virial Theorem,
      as applied to those solids for which the potential energy scales as the mean
      inverse of the inter-atomic distance, and for which on compression the entropy
      change is small.

PMID- 16592027
TI  - Purification of an ion-stimulated adenosine triphosphatase from plant roots:
      association with plasma membranes.
AB  - A membrane-bound adenosine triphosphatase (EC 3.6.1.3) that requires Mg(++) and
      that is stimulated by monovalent ions has been purified 7- to 8-fold from
      homogenates of oat (Avena sativa L. Cult. Goodfield) roots by discontinuous
      sucrose-gradient centrifugation. The enzyme was substrate specific; adenosine
      triphosphate was hydrolyzed 25 times more rapidly than other nucleoside
      triphosphates. The membrane fraction containing adenosine triphosphatase was
      enriched in plasma membranes, which were identified by the presence of a glucan
      synthetase (EC 2.4.1.12), a high sterol to phospholipid ratio, and by a stain
      consisting of periodic acid, chromic acid, and phosphotungstic acid that is
      specific for plant plasma membranes. Oat-root plasma membranes and the associated
      adenosine triphosphatase were purified on either a 6-layer discontinuous sucrose
      gradient or on a simplified gradient consisting of only two sucrose layers.These
      results represent the first demonstration that plant plasma membranes contain an
      adenosine triphosphatase that is activated by monovalent ions, and this finding
      further implicates the enzyme in the absorption of inorganic ions by plant roots.

PMID- 16592028
TI  - Circulation on the continental shelf.
AB  - A simple analysis is presented of a hypothetical shelf-circulation that could
      apply to the eastcoast continental shelf of North America under winter
      conditions.

PMID- 16592029
TI  - Algebraic Structure of Linear Dynamical Systems. III. Realization Theory Over a
      Commutative Ring.
AB  - The realization theory linear dynamical systems, previously developed over a
      field, are extended to a large class of commutative rings. The principal result
      is that the existence criterion for a finite realization extends without
      modification from a field to a Noetherian integral domain.

PMID- 16592030
TI  - On the primary nature of fluorescence yield changes associated with
      photosynthesis.
AB  - Absorbance changes of C-550 and cytochrome b(559), and fluorescence-yield changes
      were measured during irradiation of chloroplasts at -196 degrees . The photo
      reduction of C-550 proceeded more rapidly than the photo-oxidation of cytochrome
      b(559), and the fluorescence-yield change had similar kinetics to the cytochrome
      b(559) change. The fluorescence yield of chloroplasts exposed to a 16-musec flash
      at -196 degrees did not increase during the flash, but increased in the dark
      after the flash. Both of these experiments indicate that the fluorescence yield
      follows the dark reduction of the primary electron donor of Photosystem II, not
      the photoreduction of the acceptor. This explanation would also account for the
      recent results of Mauzerall [Proc. Nat. Acad. Sci. USA (1972) 69, 1358-1362]
      showing that the fluorescence yield of chloroplasts at room temperature requires
      about 20 musec to reach a maximum after a very brief flash.

PMID- 16592031
TI  - Fluidity: a general theory.
AB  - The equation varphi = B(V - V(o))/V(o), which reproduces the fluidity of simple
      liquids accurately over ranges between freezing and boiling points, is here shown
      to hold to pressures of at least 500 atm, and nearly to critical volumes.
      Fluidity can vary continuously above the critical region into that of compressed
      gas, where the parameter B becomes a function of temperature.The parameter V(o)
      is a "corresponding states" fraction of the critical molal volume. It is
      identical with the molal volume of the solid only in cases where molecules are
      free to rotate as they do in the liquid.Parameter B is a measure of the extent to
      which the external momentum that produces viscous flow is absorbed by the
      molecules of the liquid. Such damping can result from molecular mass, e.g., Ne,
      Ar, Kr; flexibility, normal alkanes; or rotational inertia, SiBr(4) against
      SiCl(4).

PMID- 16592032
TI  - Some thermodynamic relations at the critical point in liquid-vapor systems.
AB  - The relation of the symmetry of the thermodynamic functions with respect to the
      critical density rho(c) to the analyticity of the chemical potential above the
      critical temperature is discussed with the aid of thermo-dynamic considerations.
      Special consideration is given to the differential coefficients
      ([unk](2)mu/[unk]T(2))rho and ([unk](2)P/[unk]T(2))rho. The discussion is
      extended to the two-phase region, and some of the relations between critical
      exponents are analyzed. A proof is given that the vapor-pressure curve joins
      smoothly with the critical isochore. The behavior of the entropy along the
      coexistence curve is considered. Finally, an argument is presented that the
      Griffiths-Liberman inequality gamma' >/= beta(delta - 1) is an equality.

PMID- 16592033
TI  - An asymbiotic nitrogen-fixing bacterium from the root environment of corn.
AB  - Examination of root systems and adhering soil associated with unusually green
      corn plants from nitrogen-deficient areas in fields has revealed higher acetylene
      reducing activities than comparable root systems of chlorotic plants that
      appeared to be nitrogen deficient. From the root systems with acetylene-reducing
      activity, N(2)-fixing Enterobacter cloacae were isolated. Pure cultures of the
      organism grown in a medium lacking added fixed nitrogen reduced acetylene to
      ethylene and used N(2) as a sole source of nitrogen under anaerobic conditions.
      Acetylene reduction was strikingly inhibited by 0.04 atm or greater partial
      pressures of O(2); however, the bacteria maintained appreciable acetylene
      reducing rates in medium exposed to partial pressures of O(2) ranging from 0.005
      to 0.015 atm. Nitrogenase activity in cell-free extracts of the bacterium was
      dependent upon Na(2)S(2)O(4) and an ATP-generating system. Some environmental
      conditions expected to influence N(2) fixation by free-living N(2)-fixing
      bacteria on root surfaces of nonlegumes are discussed.

PMID- 16592034
TI  - Specificity of the cis-Isomers of Inhibitors of Uredospore Germination in the
      Rust Fungi.
AB  - The cis- but not the trans-isomers of the natural inhibitors, methyl ferulate and
      methyl 3,4-dimethoxycinnamate, inhibit germination of the uredospores of wheat
      stem rust. Minimum concentrations for 50% inhibition are about 7 and 140 nM,
      respectively. Ultraviolet radiation activates the trans-isomers by partial
      conversion to the cis-forms, and partially inactivates the cis-form by the
      reverse transformation. About 100 molecules of the germination stimulant, n-nonyl
      alcohol, are required per molecule of methyl cis-ferulate to overcome inhibition
      and restore 50% germination. Seasonal and age differences in sensitivity of
      spores to inhibitor may be related to variations in content of stimulant.

PMID- 16592035
TI  - Mutants that produce nitrogenase in the presence of ammonia.
AB  - Mutants of Azotobacter vinelandii that fix N(2) in the presence of excess NH(4)
      (+) have been isolated. A mutant that was unable to synthesize component I and
      component II of nitrogenase was spontaneously reverted to the N(2)-fixing
      phenotype. Of 21 revertants picked, 7 revertants were not as sensitive as the
      wild type to repression. A derepressed mutant is as sensitive as the wild type to
      growth inhibition by 2-methylalanine in the presence of glucose.

PMID- 16592036
TI  - Axial Presentations of Regular Arcs on M(n).
AB  - THEOREM 1. Let M(n) be a Riemannian manifold of class C(m), m > 0. On M(n) let g
      be a simple compact, sensed, regular arc whose local coordinates are functions of
      class C(m) of the algebraic arc length s, measured along g from a prescribed
      point of g. There then exists a presentation (F: U, X) [unk] [unk]M(n) such that
      g [unk] X, and each point p(s) of g is represented in the euclidean domain U by
      coordinates (x(1),...,x(n)) = (s,0,...,0).

PMID- 16592037
TI  - Systematics for elastic scattering of elementary particles.
AB  - The function (do/dlnt)((1/2)) against (t)((1/2)) gives rise to a scaling law for
      elastic scattering of elementary particles on protons, for barycentral angles
      from 0 to 90 degrees , and for laboratory momenta from 5 to 25 GeV/c.

PMID- 16592038
TI  - Stereochemical Control of Valence and Its Application to the Reduction of
      Coordinated NO and N(2).
AB  - The electronic structures of transition metal complexes of NO are controlled by
      the stereochemistry about the metal atom (stereochemical control of valence). The
      six-coordinate complex, trans-[CoNO(NCS)-(C(6)H(4) [As(CH(3))(2)](2))(2)](+),
      consists of [Co(III)-(N=O(-))](2+) (angle(Co-N-O) = 135 degrees ), while the
      pentacoordinate trigonal bipyramidal complex,
      [CoNO(C(6)H(4)[As(CH(3))(2)](2))(2)] (2+), is best formulated as [Co(I)-(N
      identical withO(+)](2+) (angle(Co-N-O) = 179 degrees ). Evidence indicates that
      complexes of (NO)(+) and N(2) are electronically similar. Hence, the principles
      of stereochemical control of valence may be applied to metal complexes of N(2).
      In a linearly coordinated M(n) m(N identical withN) complex, valence electrons
      can be transferred from the metal to the N(2) ligand producing a bent,
      protonated, and/or metallated M(n+2)-(N=N(2-)) complex. This reduction of N(2)
      can be effected by the addition of an appropriate ligand to M or by a change in
      the coordination geometry about M. Stereo-chemical control of valence leads to
      the rejection of one of the previously proposed mechanisms for reduction by
      nitrogenase.

PMID- 16592039
TI  - Computer simulation of fluorescence depolarization due to brownian motion.
AB  - A computer program has been written to simulate the Brownian motion of rigid
      fluorescent molecules. The time dependence of the fluorescence polarization
      anisotropy as generated by this simulation is in agreement with that predicted by
      the recent theoretical treatment of Belford, Belford, and Weber (Proc. Nat. Acad.
      Sci. USA (1972) 69, 1392-1393). The program thus serves as a verification of
      their equation. It is being generalized to cover the case of nonrigid molecules.

PMID- 16592040
TI  - Hilbert transforms in yukawan potential theory.
AB  - If H denotes the classical Hilbert transform and Hu(x) = v(x), then the functions
      u(x) and v(x) are the values on the real axis of a pair of conjugate functions,
      harmonic in the upper half-plane. This note gives a generalization of the above
      concepts in which the Laplace equation Deltau = 0 is replaced by the Yukawa
      equation Deltau = mu(2)u and in which the Cauchy-Riemann equations have a
      corresponding generalization. This leads to a generalized Hilbert transform
      H(mu). The kernel function of this new transform is expressable in terms of the
      Bessel function K(0). The transform is of convolution type.

PMID- 16592041
TI  - Perturbed angular correlation study of a haptenic molecule.
AB  - The angular correlation of the 173-247 keV gamma-ray cascade after the electron
      capture decay of (111)In is strongly perturbed when the 1-p-nitrophenyl
      ethylenediaminetetraacetate chelate of (111)In(8+) is added to a solution
      containing rabbit antibody to dinitrophenyl groups. The radioactive chelate can
      be displaced by the addition of dinitrophenyllysine or unlabeled chelate. The
      average association constant between the antibody and the labeled chelate has
      been estimated from perturbed angular correlation measurements; this value is
      compared to the results of equilibrium dialysis. These experiments provide good
      evidence that information concerning macromolecular behavior can be obtained from
      perturbed angular correlation experiments that use chemically specific labels.

PMID- 16592042
TI  - Problems on periodic simple continued fractions.
AB  - Let N be a positive non-square integer and a(1),a(2),...,a(3) be the partial
      denominators in the period of length s = s(N) of the continued fraction for
      radicalN. Also let Sigma(N) = a(3) - a(3-1) + -... +/- a(1), and let h(d) be the
      class-number of Q( radicald). Hirzebruch (unpublished) recently found the
      surprising theorem (which is a special case of more general results): If p is a
      prime identical with3(4) and p > 3, then h(p) = 1 implies that Sigma(p) = 3h(
      p).This result led to related conjectures presented herein.

PMID- 16592043
TI  - Notes on "doomsday models".

PMID- 16592044
TI  - Extranuclear Temperature-Sensitive Lethality in Nicotiana tabacum L.
AB  - Tobacco seedlings from progeny of a single aberrant plant, either self-fertilized
      or used as the female in crosses, failed to become autotrophic at 13 degrees day
      and 8 degrees night temperatures, but grew normally at 26 degrees day and 20
      degrees night temperatures. After initial normal growth at 26 degrees day and 20
      degrees night temperatures, autotrophic plants from the aberrant line also died
      after subsequent exposure to 13 degrees day and 8 degrees night temperatures. The
      temperature-sensitive lethality was transmitted only through the female parent.
      When seedlings were grown at normal 26 degrees day and 20 degrees night
      temperatures, mutant selfs, normal selfs, and reciprocal F(1) hybrids were
      indistinguishable.

PMID- 16592045
TI  - Structure and chemical synthesis of a biologically active form of renilla (sea
      pansy) luciferin.
AB  - The structure of a biologically active form of Renilla (sea pansy) luciferin has
      been elucidated; this structure, confirmed by total chemical synthesis, is 3,7
      dihydro-2-methyl-6-(p-hydroxyphenyl)-8-benzylimidazo [1,2-a] pyrazin-3-one. In
      the natural compound the methyl group at the 2 position is replaced by an
      unknown, more complex group. For this reason the synthetic compound is 10% as
      active as the natural compound in producing light with Renilla luciferase.
      However, the spectral properties of the two compounds are identical. In addition
      the rates of the luminescent reaction with both compounds are similar, and the
      color of the light produced is identical in each case.A compound isolated from
      the calcium-triggered photoprotein aequorin has been identified by Shimomura and
      Johnson [(1972) Biochemistry 11, 1602] to be 2-amino-3-benzyl-5-(p
      hydroxyphenyl)pyrazine. This compound forms an integral part of the structure of
      Renilla luciferin. This, and other evidence, suggests that the structure
      elucidated for Renilla luciferin is a more general one associated with the
      luciferins of most, if not all, bioluminescent coelenterates.

PMID- 16592046
TI  - Thermal motion and forced migration of colloidal particles generate hydrostatic
      pressure in solvent.
AB  - A colloidal solution of ferrite particles in an osmometer has been used to
      demonstrate that the property that propels water across the semipermeable
      membrane is the decrease in hydrostatic pressure in the water of the solution. A
      magnetic field gradient directed so as to force the ferrite particles away from
      the semipermeable membrane of the osmometer and toward the free surface of the
      solution enhanced the colloidal osmotic pressure. The enhancement of this
      pressure was always exactly equal to the augmentation of the pressure as measured
      by the outward force of the particles, against the area of the free surface.
      Contrariwise, directing the magnetic field gradient so as to force the ferrite
      particles away from the free surface and toward the semipermeable membrane
      diminished the colloidal osmotic pressure of the solution. For a sufficiently
      forceful field gradient, the initial colloidal osmotic pressure could be
      negative, followed by an equilibrium pressure approaching zero regardless of the
      force of the particles against the membrane. Thus, the osmotic pressure of a
      solution is to be attributed to the pressure in the solvent generated in
      opposition to the pressure of the solute particles caused by their interaction
      with the free surface (Brownian motion and/or an external field force), or by
      their viscous shear when they migrate through the solvent, or both.

PMID- 16592047
TI  - Biosynthesis of the photosystem I chlorophyll-protein complex in greening leaves
      of higher plants.
AB  - Biosynthesis of photosystem I chlorophyll-protein complex, derived from
      chloroplast lamellae solubilized with Triton X-100, was examined in rapidly
      greening primary leaves of the jack bean. It was found that the chlorophyll/P700
      ratio of the complex was low (35/1) in the early stages of greening, and
      increased steadily to a stable level (75/1) during continued chloroplast
      development. It is suggested from these results that in the initial stages of
      greening, and probably throughout synthesis, the P700-chlorophyll-protein
      molecules are first inserted into the developing lamellae, and those photosystem
      I chlorophyll-protein molecules functioning solely in a light-harvesting capacity
      are added subsequently.

PMID- 16592048
TI  - Photooxidation of chlorophyll B by quinones studied by chemically-induced dynamic
      nuclear polarization.
AB  - The photooxidation of chlorophyll b by 1,4-benzoquinone and 2,6-dimethyl-1,4
      benzoquinone was investigated by the technique of chemically-induced dynamic
      nuclear polarization. Polarization of the proton magnetic resonance lines of the
      quinone was detected. A mechanism for the photooxidation was postulated that
      invokes the reaction of the quinone with the excited singlet state of the
      chlorophyll to form a radical pair. This mechanism, together with a theoretical
      model and parameters taken from the literature, yields a theoretical proton
      magnetic resonance spectrum for the polarized quinone that agrees well with that
      observed experimentally.

PMID- 16592049
TI  - The crystal structures of 2,5-piperazinediones having epipolysulfide bridges
      between c3 and c6: the structures of n,n'-dimethyl-3,6-epitetrathio-2,5
      piperazinedione.
AB  - The crystal and molecular structure of N,N'-dimethyl-3,6-epitetrathio-2,5
      piperazinedione (C(6)H(8)O(2)N(2)S(4)) has been determined from three-dimensional
      x-ray diffraction data collected by counter techniques. The substance
      crystallizes in the orthorhombic space group Fdd2, with a = 15.352(5), b =
      20.432(7), and c = 6.635(2) A; V = 2081.2(8) A(3), D(meas) = 1.72(2) g/cm(3), and
      z = 8 molecules per unit cell. The molecule lies on a crystallographic 2-fold
      axis, the piperazinedione ring is in the boat conformation, and the deviation
      from planarity is 18 degrees . The bonds of the tetrasulfide chain alternate in
      length so that the S-S distances are 2.0244(9), 2.076(1), and 2.0244(9) A. The
      structural data were refined by least-squares methods to an R(F) of 2.5% by use
      of the 1089 independent reflections (2theta </= 71 degrees ; MoKalpha) for which
      F(0) (2) >/= 3sigma (F(0) (2)). Since this molecule is chemically identical with
      the active center of the recently isolated natural product sporidesmin G, our
      structural study constitutes a description of the epitetrathio-2,5
      piperazinedione fragment of that molecule.

PMID- 16592050
TI  - Photophosphorylation by monomolecular films at an air-water interface.
AB  - An acetone extract of chloroplast particles, when layered on an aqueous surface,
      exhibited light-dependent phosphorylation. Studies with the firefly-tail enzyme
      assay, as well as with (32)P-labeled inorganic phosphate, show an initial release
      of adenosine triphosphate (a step that is apparently only light-triggered),
      followed by a light-dependent uptake of the labeled inorganic phosphate into
      adenosine diphosphate and adenosine triphosphate.

PMID- 16592051
TI  - Surface circulation of lakes and nearly land-locked seas.
AB  - The pattern of surface circulation has been mapped for more than 40 lakes,
      marginal seas, estuaries, and lagoons. All are within the northern hemisphere,
      and all except one are known to have a counterclockwise pattern. This consistent
      pattern is attributed to the drag of wind blowing across the bodies of water.
      Warmer surface water is displaced to the right-hand shore zone (facing downwind),
      where it produces greater surface turbulence and, thus, greater wind drag. This
      effect leads to counterclockwise water circulation regardless of the direction
      and, within limits, the duration of the wind.

PMID- 16592052
TI  - Hydrophobicity of Long Chain n-Alkyl Carboxylic Acids, as Measured by Their
      Distribution Between Heptane and Aqueous Solutions.
AB  - Previous data for the distribution of the n-alkyl carboxylic acids between
      aqueous buffers and heptane have suggested that the free energy of transfer
      between the two solvents does not increase with the length of the alkyl chain
      beyond palmitic acid, indicating a limit to the hydrophobicity of the alkyl chain
      at a length of about 15 carbon atoms. It is shown in this paper that previous
      measurements were influenced by unexpectedly strong pH-dependent association of
      the long-chain acids in the aqueous phase. Under conditions where such
      association becomes negligible, the free energy of transfer becomes a strictly
      linear function of alkyl chain length for all acids up to behenic acid
      (C(21)H(43)COOH).

PMID- 16592053
TI  - Detection of a Free Radical in the Primary Reaction of Chloroplast Photosystem
      II.
AB  - Electron paramagnetic resonance (EPR) spectroscopy has revealed a new free
      radical signal produced by illumination of spinach chloroplasts at 77 degrees K.
      This signal is observed only when an oxidant (ferricyanide) is added to the
      chloroplast suspension in the dark before illumination. The EPR signal is
      produced at 77 degrees K by illumination with 645-nm monochromatic light capable
      of activating Photosystem II but not with 715-nm illumination capable of
      activating Photosystem I. Furthermore, since the signal shows a relative increase
      in chloroplast fragments enriched in Photosystem II but is absent in chloroplast
      fragments enriched in Photosystem I, we conclude that this new EPR signal is
      associated with the primary photoact of Photosystem II in chloroplasts. On the
      basis of the measured EPR parameters (g = 2.0026 +/- 0.0002, linewidth = 8 G), it
      is suggested that the signal may be associated with the reaction-center
      chlorophyll of Photosystem II.

PMID- 16592054
TI  - A stable solid model for protein sulfenyl iodides.
AB  - The first simple sulfenyl iodide that is a pure stable crystalline solid is
      reported. This product, ISCMe(2)CH(NHCbz)CONH-Ph-p-Cl(10), contains linkages that
      simulate the two peptide linkages vicinal to the -SI moiety in a protein sulfenyl
      iodide. Unlike typical simple sulfenyl iodides, solid 10 remains unchanged at
      ambient conditions for more than ten weeks; however, it is quite reactive in
      solution. Under proper circumstances, therefore, a sulfenyl iodide is proved to
      be a stable but highly reactive species. The model 10 and related compounds
      should afford prospects for better understanding of the unusual stabilities of
      certain protein sulfenyl iodides and of ways in which other such compounds may
      function in mediating iodination reactions in the thyroid gland.

PMID- 16592055
TI  - Reduction of acetylene and hydrazine with a molybdenum-glutathione complex.
AB  - Crystalline preparations of a molybdenum-glutathione complex catalyze the
      reduction of acetylene to ethylene in the presence of borohydride. The reaction
      proceeds at rates up to 6 mol of C(2)H(2) produced per min per mol of bound Mo,
      which is 4% of the activity of a quantity of nitrogenase with an equivalent
      amount of Mo. The activity of the complex is enhanced 100-fold by ATP, but the
      addition of ADP has no effect. Stimulation in activity by GTP is about the same
      as that by ATP, and the effects of CTP or UTP are considerably less. Inhibition
      of acetylene-reduction activity by the addition of 32 mM orthophosphate was 14%,
      by 32 mM pyrophosphate 62%, by 0.2 atm of O(2) 65%, and by 0.5 atm of CO 12%; 0.5
      atm of H(2) had no effect. The molybdenum-glutathione complex also catalyzes the
      reduction of hydrazine to ammonia in a reaction that is dependent upon
      borohydride. The reaction is enhanced about 7-fold by ATP and proceeds at a rate
      of 2 mol of NH(3) produced per min per mol of bound Mo.

PMID- 16592056
TI  - Downwind and upwind effects in the Arizona cloud-seeding experiment.
AB  - The principal subject of this report is a comparison of precipitation on days
      with seeding with that without seeding, averaged over those rain gauges that on
      each particular day were "downwind," "upwind," or to the sides. Two estimates of
      relevant wind directions are used, based on successive radiosondes at Tucson that
      bracketed the scheduled time of seeding. By use of these radiosondes, the
      apparent effects of seeding on rain in downwind localities 90-180 miles (145-290
      km) away from target were found to be an apparent 45% loss of rain (P = 0.002)
      and an apparent 34% loss of rain (P = 0.028), respectively. Other results
      indicate considerable geographic heterogeneity.

PMID- 16592057
TI  - "Metodo rapido" for finding real quadratic fields of class-number 1.
AB  - The authors state and prove a rapid criterion to determine whether the class
      number of certain real quadratic fields is 1.

PMID- 16592058
TI  - 8-bromoadenosine 3':5'-cyclic monophosphate as a promoter of cell division in
      excised tobacco pith parenchyma tissue.
AB  - 8-Bromoadenosine 3':5'-cyclic monophosphate, when used in association with an
      auxin, can completely replace the cell-division-promoting activity of either a
      cytokinesin or a 6-substituted adenylyl cytokinin in excised tobacco pith
      parenchyma tissue. The 8-bromo derivative of adenosine 3':5'-cyclic monophosphate
      was found to be far more resistant to degradation by plant adenosine 3':5'-cyclic
      monophosphate phosphodiesterases than was adenosine 3':5'-cyclic monophosphate.
      These findings appear to provide further support for the suggestion made earlier
      that the cytokinesins, which are potent inhibitors of both plant and animal
      adenosine 3':5'-cyclic monophosphate phosphodiesterases, exert their cell
      division-promoting effects as regulators of adenosine 3':5'-cyclic monophosphate.

PMID- 16592059
TI  - Influence of Leaving-Group Electronic Effect on alpha-Chymotrypsin: Catalytic
      Constants of Specific Substrates.
AB  - Rate constants and binding constants for the alpha-chymotrypsin-catalyzed
      hydrolysis of N-acetyltyrosine, tryptophan, and phenylalanine anilides are
      presented. Both k(cat) and K(m) are independent of electronic effects in the
      substrate over a range of 9.8 orders of magnitude (as measured by pK of the
      leaving group). Similarly, K(m) is independent of charge and orientation about
      the alpha-carbon for various substrates and pseudo-substrates. These results are
      not consistent with the pretransition state protonation hypothesis; instead, they
      are discussed in terms of a tetrahedral intermediate that is thermodynamically
      less stable than the Michaelis complex.

PMID- 16592060
TI  - The energy of substituted ethanes. Asymmetry orbitals.
AB  - The leading terms in the energy of a general substituted ethane are derived in
      explicit form as a function of the torsional angle theta, the substituent
      electronegativities, and their mutual overlaps. The energy is found to be the sum
      of all four overlaps between pairs of asymmetry orbitals, and satisfies the
      requisite symmetry properties.

PMID- 16592061
TI  - p-Algebras of Arbitrary Exponents.
AB  - To a purely inseparable Galois field extension C over A we associate a certain
      differential polynomial ring D. We show that all central simple A-algebras that
      contain C as a maximal commutative subalgebra can be obtained from D by factoring
      out certain ideals determined by Witt vectors.

PMID- 16592062
TI  - Nuclear Magnetic Resonance Shift Reagents: Abnormal C Shifts Produced by
      Complexation of Lanthanide Chelates with Saturated Amines and n-Butyl Isocyanide.
AB  - Lanthanide-induced shfits of (13)C nuclear magnetic resonances are reported for
      several amines and n-butyl isocyanide. Contact contributions to such shifts,
      especially of beta carbons, are clearly important for the chelates of Eu(+3) and
      Pr(+3). The importance of contact terms is shown to change in a rather
      predictable manner with the structure of the amine.

PMID- 16592064
TI  - Competition among plants.

PMID- 16592063
TI  - Nicotinic Acid as a ligand affecting leghemoglobin structure and oxygen
      reactivity.
AB  - A small molecule, hitherto called X, which is present in legume root nodules and
      ligates reversibly to the monomeric protein, leghemoglobin, with formation of a
      hemochrome structure, is identified as nicotinic acid. The binding constants at
      pH 5.3 are K = 7.3 x 10(5) M(-1) and K = 3.0 x 10(4) M(-1) for combination of
      nicotinic acid with ferric and ferrous leghemoglobin, respectively. This high
      affinity binding of ligand requires an unsubstituted pyridine ring nitrogen atom
      and an ionized carboxyl group in the 3-position of the ring. Binding of nicotinic
      acid is favored at acid pH and is reflected by diminished apparent affinity of
      leghemoglobin for oxygen.

PMID- 16592065
TI  - Ethylene in plant growth.
AB  - Ethylene inhibits cell division, DNA synthesis, and growth in the meristems of
      roots, shoots, and axillary buds, without influencing RNA synthesis. Apical
      dominance often is broken when ethylene is removed, apparently because the gas
      inhibits polar auxin transport irreversibly, thereby reducing the shoot's auxin
      content just as if the apex had been removed. A similar mechanism may underly
      ethylene-induced release from dormancy of buds, tubers, root initials, and seeds.
      Often ethylene inhibits cell expansion within 15 min, but delays differentiation
      so that previously expanding cells eventually grow to enormous size. These cells
      grow isodiametrically rather than longitudinally because their newly deposited
      cellulose microfibrils are laid down longitudinally rather than radially.
      Tropistic responses are inhibited when ethylene reversibly and rapidly prevents
      lateral auxin transport. In most of these cases, as well as certain other
      instances, ethylene action is mimicked by application of an auxin, since auxins
      induce ethylene formation. Regulation by ethylene extends to abscission, to
      flower formation and fading, and to fruit growth and ripening. Production of
      ethylene is controlled by auxin and by red light, auxin acting to induce a labile
      enzyme needed for ethylene synthesis and red light to repress ethylene
      production. Numerous cases in which a response to red light requires an
      intervening step dependent upon inhibition of ethylene production have been
      identified. Ethylene action requires noncovalent binding of the gas to a metal
      containing receptor having limited access, and produces no lasting product. The
      action is competitively inhibited by CO(2), and requires O(2). Ethylene is
      biosynthesized from carbons 3 and 4 of methionine, apparently by a copper
      containing enzyme in a reaction dependent upon an oxygen-requiring step with a
      K(m) = 0.2% O(2). The oxidative step appears to be preceded by an energy
      requiring step subsequent to methionine formation.

PMID- 16592066
TI  - The use of protoplasts for genetic research.

PMID- 16592067
TI  - Unipotent groups in invariant theory.
AB  - The finite generation of the ring of invariants of a special class of unipotent
      groups is established-namely, unipotent radicals of parabolic subgroups.

PMID- 16592068
TI  - Biosynthesis of cytokinins in cytokinin-autotrophic tobacco callus.
AB  - A cytokinin-autotrophic strain of tobacco callus contained cytokinin-active
      compounds with chromatographic mobilities on Sephadex LH-20 corresponding to
      ribosylzeatin, zeatin, and 6-Delta(2)-isopentenylaminopurine. Zeatin, the
      apparent major cytokinin, was estimated to be present at a concentration of 10(
      4) mumol/kg of tissue. Cytokinin-autotrophic callus supplied with [(14)C]adenine
      produced radioactive components with the same chromatographic properties as
      zeatin and 6-Delta(2)-isopentenylaminopurine. These components were not obtained
      from cytokinin-dependent tissue supplied with [(14)C]adenine in the same manner.

PMID- 16592069
TI  - Biological and molecular evidence for the transgenosis of genes from bacteria to
      plant cells.
AB  - Specialized transducing phages (lambda and varphi80) have been used as vectors in
      the transfer of genes (wild type and mutant) from the bacterium Escherichia coli
      to haploid cell lines of the plants Lycopersicon esculentum and Arabidopsis
      thaliana. The overall phenomenon of transfer, gene maintenance, transcription,
      translation, and function has been termed transgenosis. Transgenosis of galactose
      and lactose operon genes was detected by survival and growth of the plant cells
      on defined medium with galactose and lactose as sole sources of bulk carbon.
      Phages carrying a defective operon, unrelated bacterial genes, or no bacterial
      genes, do not affect the normal result of death on these media, nor do they
      prevent growth on optimal growth media. Transgenosis of the E. coli gene z (lac
      operon) was confirmed by a biochemical-immunological test specific for E. coli
      beta-galactosidase. Plant cells were unable to effectively suppress an E. coli
      nonsense mutation. The E. coli mutant suppressor gene, supF(+), specifies
      insertion of tyrosine at amber (UAG) nonsense codons. Introduction of supF(+)
      results in a lethal transgenosis on medium normally optimal for plant cell
      growth. It is concluded that amber codons are vital to the life of plant cells.
      Differentiating cells of A. thaliana were not affected by supF(+).

PMID- 16592070
TI  - Higher-Order Curvature and Local Solvability of D(theta).
AB  - Let E and F be vector bundles and D:E --> F an operator of order k. We associate
      a sequence of invariants ((l))(D), l >/= 0 with D which generalize the concept of
      curvature in a natural way. In the case where D = D(theta) is the differential
      operator of a connection theta on a vector bundle E, ((1))(D(theta)) is the
      classical curvature. Furthermore, we find an interesting geometric interpretation
      for ((2))(D(theta)). Finally, given regularity assumptions, we find, with the aid
      of these invariants, necessary and sufficient conditions for local solvability of
      D(theta).

PMID- 16592071
TI  - Fluctuation spectroscopy: determination of chemical reaction kinetics from the
      frequency spectrum of fluctuations.
AB  - The kinetic parameters of a chemical reaction were obtained from analysis of the
      frequency spectrum of the fluctuations (i.e., "noise") in the concentrations of
      the reactants. In "fluctuation spectroscopy," no external perturbation is applied
      and the system remains in macroscopic chemical equilibrium during the experiment.
      Results obtained by this method for the dissociation reaction of beryllium
      sulfate agree well with those obtained by relaxation methods in which the
      approach to equilibrium is analyzed. Other noise sources not originating from a
      chemical reaction were observed and analyzed. The most prominent of these arose
      from the flow of an electrolyte through a capillary. The method of fluctuation
      spectroscopy should be applicable to problems of physical, chemical, and
      biological interest.

PMID- 16592072
TI  - Facilitation of inhibition in the compound lateral eye of limulus.
AB  - In the compound eye of Limulus the inhibitory effect of a burst of impulses from
      one group of ommatidia on the response of a neighboring ommatidium is greater
      when that burst is preceded by another burst of impulses. This facilitation of
      inhibition decays slowly, with a time constant of several seconds. Facilitation
      of inhibition accumulates as the number of impulses in the first burst increases,
      but there is a maximum that it cannot exceed. The facilitation is localized; one
      group of ommatidia does not facilitate the inhibition exerted by another group.
      The mechanism of this facilitation may be similar to that which has been
      postulated for facilitation of excitatory influences at the neuromuscular
      junction.

PMID- 16592073
TI  - Nuclear magnetic resonance shift reagents: evidence for different mechanisms of
      contact contributions to C shifts induced by nickel and cobalt acetylacetonates
      with saturated amines and alcohols.
AB  - The pattern of (13)C and (1)H nuclear magnetic resonance (NMR) shift changes
      produced by complexation of cobalt and nickel acetylacetonates with amines and
      alcohols indicates that there is more than one mode of operation of the contact
      interaction. A large effect with alternating signs is important at the alpha and
      beta carbons, but this effect seems to be overlaid by another influence that
      appears to fall off monotonically as one proceeds away from the site of
      complexation.

PMID- 16592074
TI  - Ultraviolet patterns on rear of flowers: basis of disparity of buds and blossoms.
AB  - Flowers of Jasminium primulinum and Hypericum spp. have ultraviolet patterns on
      the reverse surface of the corolla. Those areas of the surface that are exposed
      to the outside in the bud are ultraviolet absorbent, whereas the portions that
      come into view at maturity in the open blossom are ultraviolet reflectant. Buds
      and blossoms, as a result, appear different in color to insects sensitive to
      ultraviolet light. Experimental evidence indicates that the ultraviolet-absorbent
      quality of the outer surface of the bud is a consequence of exposure itself,
      attributable possibly to a "sun tanning" effect.

PMID- 16592075
TI  - Generalized isoperimetric inequalities.
AB  - A new class of isoperimetric inequalities is described and illustrated.

PMID- 16592076
TI  - Adenosine 3':5'-Cyclic Monophosphate in Chlamydomonas reinhardtii: Isolation and
      Characterization.
AB  - Chlamydomonas reinhardtii contains a factor that can replace adenosine 3':5'
      cyclic monophosphate (cAMP) in the stimulation of rabbit-muscle protein kinase.
      The factor cochromatographs and coelectrophoreses with authentic cAMP, and is
      inactivated by beef heart cyclic nucleotide phosphodiesterase. When C.
      reinhardtii is exposed to aminophylline (theophylline(2) ethylenediamine), the
      concentration of the factor in the cells increases within 1 hr, from about 25
      pmol of cAMP equivalents per g dry weight to more than 250 pmol. Cyclic
      nucleotide phosphodiesterase activity is present in crude extract of C.
      reinhardtii and is inhibited by theophylline. We conclude that cAMP occurs in C.
      reinhardtii and that the endogenous concentration is governed at least in part by
      a theophylline-sensitive cyclic nucleotide phosphodiesterase. These findings
      provide a sound basis for attributing the effects of methylxanthines on flagellar
      function and regeneration in C. reinhardtii to the resultant elevation of
      endogenous cAMP.

PMID- 16592077
TI  - Polymorphism for interspecific cross-compatibility in phlox.
AB  - Extensive polymorphism for the cross-compatibility of Phlox pilosa with P.
      glaberrima occurs within Illinois populations. The polymorphism is genetically
      determined. Thus, there is an opportunity for selection to enhance existing cross
      compatibility barriers in areas of species contact. There is no evidence that
      selection has favored the reinforcement of such barriers.

PMID- 16592078
TI  - Self-fertilization and genetic population structure in a colonizing land snail.
AB  - The pulmonate land snail Rumina decollata in its native Mediterranean range is a
      complex of monogenic or weakly polygenic strains generated by a breeding system
      of facultative self-fertilization. One strain colonized North America and now
      occupies much of the southern United States and northern Mexico. No genetic
      variation within or among populations in the United States was detected in an
      electrophoretic analysis of proteins encoded by 25 loci. These findings emphasize
      the potential for adaptive convergence in the genetic systems of hermaphroditic
      animals and plants.

PMID- 16592079
TI  - On the Relation Between lambda Lines and Phase Separations.
AB  - It has often been assumed that the slope of the isotherm involving a pair of
      secondary variable vanishes along a lambda line [for example, along a lambda line
      in the pressure-volume plane ([unk]P/[unk]V)(T) vanishes], and therefore that the
      specific heat for constant extensive variable (e.g., C(V)) has the greatest
      possible value on the lambda line and so obeys the Buckingham-Fairbank relation.
      It is shown here by a heuristic theoretical argument that in (3)He-(4)He
      solutions ([unk]mu(4)/[unk]x(3))(T) and ([unk]mu(3)/[unk]x(3))(T) probably do not
      vanish and C(x3) does not have its maximum possible value, although it may become
      infinite when x(3) --> 0. (mu(4) and mu(3) are chemical potentials of (4)He and
      (3)He and x(3) is the molefraction of (3)He). Only at the tricritical point does
      ([unk]mu(4)/[unk]x(3))(T) finally vanish and C(x3) have a value, which cannot be
      exceeded without the system's becoming unstable. In the case of the transition in
      solid NH(4)Cl the experimental facts seem to indicate that at the higher
      temperatures, where the transition is of higher order, ([unk]P/[unk]V)(T) does
      not become zero along the transition line. A statistical thermodynamic
      description of tricritical points is given, and shown to accord qualitatively
      with the experimental results for the (3)He-(4)He solutions. There is evidence
      that any singular behavior at the tricritical point in (3)He-(4)He is already
      present along the lambda line. Finally, an analysis is made of the possible
      behavior of binary liquid solutions, and it is shown that a tendency of C(V) to
      exceed its maximum value can result in a flat top on the coexistence curve.

PMID- 16592080
TI  - A 5'-Adenosine Monophosphate-Dependent Adenylate Cyclase and an Adenosine 3':5'
      Cyclic Monophosphate-Dependent Adenosine Triphosphate Pyrophosphohydrolase in
      Dictyostelium discoideum.
AB  - Cell aggregation in Dictyostelium discoideum appears to involve the production
      and detection of 3':5'-cyclic AMP. Two pertinent catalytic activities have been
      studied in concentrates from D. discoideum purified 50- to 100-fold. They are (i)
      adenylate cyclase and (ii) ATP pyrophosphohydrolase. ATP pyrophosphohydrolase
      activity converts ATP to 5'-AMP and pyrophosphate. The presence of 5'-AMP is an
      absolute requirement for adenylate cyclase activity. The presence of 3':5'-cyclic
      AMP is an absolute requirement for ATP pyrophosphohydrolase activity. Both
      activations, particularly that of ATP pyrophosphohydrolase, show narrow ranges of
      specificity and display significant cooperativities.

PMID- 16592081
TI  - Asymptotic Formula for the Coordinates of the Zeros of Sections of the Zeta
      Function, zeta(N)(s), Near s = 1.
AB  - The sum, Sigma1(N)n(-8) = zetaN(s), s = sigma + it, is called a section of the
      Riemann zeta function, zeta(s). Here an asymptotic formula, for large N, giving
      the location of the zeros of zetaN(s) near s = 1 will be demonstrated. In
      particular these zeros will lie in sigma < 1. Relationships between the location
      of the zeros of zetaN(s) and the zeros of zeta(s) were discovered by Turan. The
      location in sigma < 1 will also be demonstrated directly, without the asymptotic
      formula, together with results valid also when s - 1 is not small.

PMID- 16592082
TI  - Racemization reaction of aspartic Acid and its use in dating fossil bones.
AB  - In the time interval datable by radiocarbon, and at the temperatures of most
      archeological sites, a substantial amount of racemization of aspartic acid takes
      place. By determination of the amount of racemization of aspartic acid in bones
      from a particular location which have been dated by the radiocarbon technique, it
      is possible to calculate the in situ first-order rate constant for
      interconversion of the L- and D enantiomers of aspartic acid. Once this
      "calibration" has been calculated, the reaction can be used to date other bones
      from the deposit that are either too old to be dated by radiocarbon or that are
      too small for radiocarbon dating. The only assumption required with this approach
      is that the average temperature experienced by the "calibration" sample is
      representative of the average temperature experienced by older samples. This
      "calibration" technique is used herein to date bones from the Olduvai Gorge area
      in Tanzania, Africa.

PMID- 16592083
TI  - An informative solution to a seismological inverse problem.
AB  - Preliminary results are presented that infer that 2 sec should be added to the
      tabular values for P phases and 4 sec to the tabular values for S phases of
      seismic travel times. From seismic evidence, the radius of the inner core of the
      Earth is 1229-1250 km; the radius of the outer core is 3482-3485 km. Data are
      presented relating resolving power with error of measurement for the Earth's
      mantle.

PMID- 16592084
TI  - An ecological theory for the sudden origin of multicellular life in the late
      precambrian.
AB  - According to modern ecological theory, high diversity at any trophic level of a
      community is possible only under the influence of cropping. Until herbivores
      evolved, single-celled algae of the Precambrain were resource-limited, and a
      small number of species saturated aquatic environments. In the near-absence of
      vacant niches, life diversified slowly. Because the changes required to produce
      the first algae-eating heterotrophs were therefore delayed, the entire system was
      self-limiting. When the "heterotroph barrier" was finally crossed in the late
      Precambrian, herbivorous and carnivorous protists arose almost simultaneously,
      for no major biological differences separate the two groups. These events
      automatically triggered the formation of a series of self-propagating feedback
      systems of diversification between adjacent trophic levels. Comparable systems
      arose among multi-cellular groups, which radiated rapidly from the newly
      diversifying protist taxa. The sudden proliferation of complex food webs formed
      by taxa invading previously vacant adaptive zones produced an explosive
      diversification of life over a period of a few tens of millions of years. The
      rapid appearance of skeletons in various groups, though of special geological
      importance, was no more dramatic than other aspects of the radiation. The overall
      rate of diversification was comparable to rates for less-extensive adaptive
      radiations of the Phanerozoic.

PMID- 16592085
TI  - Classes of spatially inhomogeneous pseudodifferential operators.
AB  - One can obtain sharp information on a pseudodifferential operator p(x,D) by
      embedding the symbol p in a symbolic calculus specially designed to reflect the
      behavior of p. We sketch the development of symbolic calculi arising in this
      connection, and use our results to give simple proofs of the sharp Garding
      inequality and of sufficiency of Nirenberg-Traves' condition (P) for local
      solvability of equations of principal type.

PMID- 16592086
TI  - Isolation, Structure, and Absolute Configuration of a New Natural Insect Juvenile
      Hormone from Manduca sexta.
AB  - Two juvenile hormones are isolated from organ cultures of corpora allata of the
      tobacco hornworm moth, Manduca sexta Johannson, and are purified by high
      resolution liquid chromatography. These are identified as methyl (2E, 6E)-(10R)
      10,11-epoxy-3,7,11-trimethyl-2,6-dodecadienoate, a new natural hormone, and
      methyl (2E,6E) - (10R,11S) - 10,11 - epoxy - 3,7,11 - trimethyl-2,6
      tridecadienoate. [(14)C]Methionine is incorporated only into their
      methoxycarbonyl group. Details of the in vitro techniques and the chemical proof
      of structures are presented. The significance of the occurrence of a new juvenile
      hormone and the new techniques used for production, isolation, and identification
      are discussed.

PMID- 16592087
TI  - Minimax principles for the solution of semilinear gradient operator equations in
      hilbert space.
AB  - A new variational characterization of solutions for an important class of
      nonlinear operator equations is obtained. The result obtained is used to derive
      sharp necessary and sufficient conditions for the solvability of such operator
      equations. Examples of the applicability of the results obtained to nonlinear
      Dirichlet problems and global differential geometry are discussed.

PMID- 16592088
TI  - Application of the singular perturbation method to reaction kinetics.
AB  - The purpose of this paper is to show how to apply the singular perturbation
      method to the rate equations in reaction kinetics that involve different time
      scales. The Lindemann scheme has been chosen for illustration, and the steady
      state and equilibrium approximations used in the Lindemann scheme are discussed.

PMID- 16592089
TI  - F-deformations and f-tractions.
AB  - Let M(n) be a compact, connected topological manifold and F a continuous mapping
      of M(n) into R that is "topologically nondegenerate" in the sense of (Morse, M.
      (1959) J. d'Analyse Math., 7, 189-208). Let c be a value of F and set F(c) =
      {pinM(n)|F(p) </= c}. The topological critical points of F on F(c) are finite in
      number and can be related to the invariants of the homology groups of F(c) as in
      the differentiable case. F-Deformations and F-tractions make this possible. F
      Tractions are here defined and replace retracting deformations used in the
      differentiable case. The final relations will serve as a model for similar
      relations between critical extremals of Weierstrass integrals on Riemannian
      manifolds.

PMID- 16592090
TI  - The Role of 1N-Ethenoadenosine Triphosphate and 1N-Ethenoadenosine Monophosphate
      in Firefly Luminescence.
AB  - 1,N(6)-Ethenoadenosine triphosphate (epsilon-ATP) has been found to be inactive
      as a substrate for firefly luciferase. However, chemically synthesized luciferyl
      epsilonAMP is oxidized by luciferase and light is emitted. The color of the light
      is red in contrast to the normal yellow-green observed with luciferyladenylate.
      Although epsilonATP will not serve as a substrate in the activation reaction, the
      reversal of the activation, pyrophosphorolysis of dehydroluciferyladenylate, will
      occur with the ethenoadenosine analog.

PMID- 16592091
TI  - Biochemical basis of the resistance of sugarcane to eyespot disease.
AB  - Helminthosporoside is the host-specific toxin produced by Helminthosporium
      sacchari, the organism causing eyespot disease on sugarcane. Clones of sugarcane
      susceptible to the toxin posses a membrane protein that binds the toxin.
      Membranes of resistant clones do not bind the toxin. In this study, a binding
      protein from a susceptible clone was compared with its counterpart from a
      resistant clone. The protein from the resistant clone did not bind the toxin
      unless it was first treated with mild detergent. The two proteins are
      antigenically identical, have the same molecular weight, and each contains four
      subunits. They differ slightly in their electrophoretic mobility and vary with
      respect to four different aminoacid residues. The basis of resistance of clone
      H50-7209 to eyespot disease is directly associated with the structurally altered
      membrane-binding protein.

PMID- 16592092
TI  - A Cytoplasmic Regulatory Mutant of Euglena: Constitutivity for the Light
      Inducible Chloroplast Transfer RNAs.
AB  - An ultraviolet-induced cytoplasmic mutant (G(1)BU) of Euglena gracilis Klebs var.
      bacillaris Pringsheim is described. G(1)BU, in addition to being golden in color
      and containing smaller amounts of chlorophyll than wild type when grown in the
      light, is a regulatory constitutive mutant for the light-inducible chloroplast
      isoleucine and methionine tRNAs; i.e., these two tRNAs are present in dark-grown
      G(1)BU cells at approximately the levels present in light-grown wild-type cells.
      Six other mutants were also examined for normal control of plastid tRNA
      biosynthesis; all four of the aplastidic mutants (lacking appreciable plastid
      structures and detectable plastid DNA) are incapable of chloroplast tRNA
      biosynthesis, whereas two other color mutants that do contain plastids and
      chloroplast DNA have normal plastid tRNA regulation.

PMID- 16592093
TI  - Maximal functions and h spaces defined by ergodic transformations.
AB  - Suppose an ergodic flow acts on a probability space enabling us to introduce the
      Ergodic Hilbert transform f of f in L(p)(), 1 <== p <== infinity. H(1) is the
      class of all functions of the form f + if in L(1)(). We show that H(1) can be
      characterized in terms of a class of maximal functions; moreover, the dual space
      of H(1) is identified with a space of functions of bounded mean oscillation
      defined in terms of the flow.

PMID- 16592094
TI  - Moments of the End-to-End Vector of a Chain Molecule, Its Persistence and
      Distribution.
AB  - The persistence vector a is defined as the configurational average of the chain
      vector r connecting the ends of the molecule and expressed in a reference frame
      fixed with respect to the first two skeletal bonds. Moments of second and higher
      orders in the components of r may readily be calculated for real chains in the
      rotational isomeric state approximation, and from them the corresponding moments
      of the vector rho = r - a measured from the terminus of a. Development of the
      density distribution of rho about a is proposed as an alternative to the
      customary treatment of the density distribution of r about r = 0 on the
      assumption that this latter distribution should be (approximately) symmetric.
      Past difficulties in the analysis of cyclization equilibria involving rings of
      moderate size, such as occur in single strands of polynucleotide chains,
      conceivably may be overcome by adoption of this alternative.

PMID- 16592095
TI  - Mating Types and Macrocyst Formation in Dictyostelium discoideum.
AB  - Strains of Dictyostelium discoideum were paired in various combinations. Certain
      pairings resulted in the production of macrocysts, which are thought to be the
      sexual stage in the cellular slime molds. One selfcompatible strain was found.
      Other strains produced macrocysts only when paired with an alternate mating type.
      Two strains were found to form macrycysts when paired with either mating type but
      not alone or with each other. Several strains did not form macrocysts under any
      circumstances. Strains were graded according to their mating competency based on
      the number of macrocysts produced relative to the aggregated myxamoebae observed
      in the pairings.

PMID- 16592096
TI  - Conformations of the li-antamanide complex and na-[phe, val]antamanide complex in
      the crystalline state.
AB  - Antamanide, a cyclic decapeptide isolated from the poisonous mushroom Amanita
      phalloides, preferably complexes with Na(+), but in less polar solvents, e.g.,
      acetonitrile, also with Li(+) or K(+). The selectivity of complexation makes it
      an important model for the study of conformational requirements of ion binding.
      The conformations of the lithium antamanide complex and the Na-[Phe(4),
      Val(6)]antamanide complex have been established by x-ray diffraction analyses of
      single crystals. The two compounds are isostructural, but not isomorphous. The
      complexes are folded into a globular shape with an approximate 2-fold axis. Two
      of the peptide linkages are in the cis conformation, Pro(2)-Pro(3) and Pro(7)
      Pro(8). There are only two intramolecular hydrogen bonds. Four C==O groups have
      their O atoms directed inward to form four Li-O or Na-O ligands. The fifth ligand
      to the metal ion is provided by a solvent molecule. The conformation found in the
      crystalline state is different from any of the conformations proposed for the
      sodium antamanide complex in solution on the basis of nuclear magnetic resonance
      data.

PMID- 16592097
TI  - Heat exchnage in the black skipjack, and the blood-gas relationship of warm
      bodied fishes.
AB  - The black skipjack, Euthynnus lineatus, uses a centrally located vascular heat
      exchanger to maintain core body temperatures warmer than ambient sea water. The
      heat exchanger is composed of the dorsal aorta, the posterior cardinal vein, and
      a large vertical rete. The dorsal aorta is embedded in the posterior cardinal
      vein and is completely bathed in venous blood. Skipjack hemoglobin appears
      similar to that of the bluefin tuna in that oxygen capacity is unaffected by
      changing temperature. Temperature-insensitive hemoglobin may function in warm
      bodied fishes to prevent the premature dissociation of oxygen from hemoglobin as
      blood is warmed en route to the muscles.

PMID- 16592098
TI  - A robust confidence interval for location for symmetric, long-tailed
      distributions.
AB  - A procedure called the wave-interval is presented for obtaining a 95% confidence
      interval for the center (mean, median) of a symmetric distribution that is not
      only highly efficient when the data have a Normal distribution but also performs
      well when some or all of the data come from a long-tailed distribution such as
      the Cauchy. Use of the wave-interval greatly reduces the risk of asserting much
      less than one's data will support. The only table required is the usual t-table.
      The wave-interval procedure is definitely recommended for samples of ten or more,
      and appears satisfactory for samples of nine or eight.

PMID- 16592099
TI  - Characteristics of polarographic catalytic waves observed with bovine-serum
      albumin: kinetic or diffusion control.
AB  - Conditions are described under which the catalytic Brdicka currents observed in
      ammoniacal buffer solutions containing cobalt(III) hexammine chloride or
      cobalt(II) and very little bovine-serum albumin (0.1-0.2 muM) are purely
      kinetically controlled. Under these conditions the kinetic current at pH 9.3-10.3
      exhibits a sharp maximum followed by a decrease of the current to a well-defined
      minimum. The maximum and minimum are eliminated in the presence of 5 mM or more
      concentrated calcium chloride when a short plateau occurs at the potential of the
      maximum followed by a well-defined second wave. Both currents are kinetically
      controlled. When the albumin concentration is 2 muM or greater, the kinetic
      currents approach diffusion control, the rate of diffusion of cobalt(III) or (II)
      being close to rate determining. Under these conditions the currents become
      proportional to the cobalt(III) or (II) concentration in the concentration range
      between 25 and 200 muM.

PMID- 16592100
TI  - Predator-prey patterns.
AB  - A graph-theoretic condition is given for the existence of stable solutions to the
      Volterra-Lotka equations.

PMID- 16592101
TI  - Chlorophyll composition and photochemical activity of photosystems detached from
      chloroplast grana and stroma lamellae.
AB  - A stroma fraction that has photosystem 1 activity and grana lamellae fractions
      that have activities for both photosystems were isolated by differential
      centrifugation of a needle valve homogenate. Subsequent fractions, corresponding
      to photosystems 1 (F-1D) and 2 (F-2D) were isolated by digitonin treatment of the
      grana lamellae (P-10K) and compared with respect to their chlorophyll composition
      and electron transport activities.Fraction F-2D from grana lamellae having
      photosystem 2 activity is primarily active in photosystem 2 and contains only the
      four major forms of chlorophyll a with a predominance of chlorophyll a 677 nm.
      This fraction differs from the original grana membranes in the absence of the
      longwavelength form of chlorophyll a and in the widening of the absorption band
      of chlorophyll a 682 nm from 10.9 to 15.6 nm.Photosystem 1 particles from grana
      and stroma both have high photosystem 1 activity but differ from each other in
      the proportions of the four major forms of chlorophyll a. The short-wavelength
      forms of chlorophyll a and also chlorophyll b 650 nm in particles from grana
      lamellae comprise relatively more total area than these same forms in the
      particles from stroma. In addition, the fraction corresponding to photosystem 1
      from grana lamellae is not shifted to the long-wavelength side of the main
      absorption maximum, as compared to the photosystem 2 particles from grana and the
      original grana membrane fraction; this is usually observed in fractions that have
      photosystem 1 activity. Furthermore, the longest wavelength form of chlorophyll a
      in the photosystem 1 particles from grana is at 700 nm, while in the same
      fraction from stroma, it is at 706 nm.The half-width of the four main forms of
      chlorophyll a and both forms of chlorophyll b in the photosystem 1 fraction from
      grana is narrower than that of the corresponding forms in the same fraction from
      stroma. This may indicate a different packing of pigment molecules that are
      aggregated on the surface of membranes of these two fractions.

PMID- 16592102
TI  - Optimality of profit-including prices under ideal planning.
AB  - Although prices calculated by a constant percentage markup on all costs (nonlabor
      as well as direct-labor) are usually admitted to be more realistic for a
      competitive capitalistic model, the view is often expressed that, for optimal
      planning purposes, the "values" model of Marx's Capital, Volume I, is to be
      preferred. It is shown here that an optimal-control model that maximizes
      discounted social utility of consumption per capita and that ultimately
      approaches a steady state must ultimately have optimal pricing that involves
      equal rates of steady-state profit in all industries; and such optimal pricing
      will necessarily deviate from Marx's model of equal rates of surplus value
      (markups on direct-labor only) in all industries.

PMID- 16592103
TI  - Theoretical investigations of automimicry: multiple trial learning and the
      palatability spectrum.
AB  - We previously explored automimicry assuming that a species of prey was so
      unpalatable as to promote conditioned avoidance for a period of time after a
      predator encountered a single individual (Case 1). In this paper, we assume that
      the prey is less noxious and that two encounters are required. Case 2 allows the
      two encounters with unpalatables to be separated by any number of palatables,
      while in Case 3 the predator must encounter two unpalatables, consecutively.The
      general relationships in the three cases are similar, but the automimetic
      advantage is reduced moderately in Case 2 and greatly in Case 3. To attain the
      same automimetic advantage as in Case 1 requires an increase in the proportion of
      unpalatables, or in the induced rejection period, or both. Consequently,
      selection will tend to increase the unpalatability so that Cases 2 and 3 converge
      to Case 1.Species that are uniformly and highly unpalatable can afford to be more
      dispersed than automimetic species. Case-2 and -3 automimetic species will
      benefit greatly from gregariousness, while in Case-1 automimicry situations this
      is less important.

PMID- 16592104
TI  - Hydrogen evolution by a chloroplast-ferredoxin-hydrogenase system.
AB  - Spinach chloroplast preparations were mixed with Clostridium kluyveri hydrogenase
      and ferredoxin. Hydrogen evolution could be measured in the light in the absence
      of any added electron donors. Inhibition of the water-splitting reaction or of
      photosystem II reduced the amount of H(2) evolved more than 95%, indicating that
      H(2)O was the electron donor in this reaction. The rates of H(2) evolution
      observed were up to 20% of those measured in the presence of an oxygen-consuming
      reaction or of photosystem I electron donors. These findings indicate that
      hydrogen evolution from water and sunlight by photosynthetic processes could be a
      method for solar energy conversion.

PMID- 16592105
TI  - Internal swash and surf.
AB  - 114 temperature sections, each containing an average of 10 bathythermograms, show
      that internal waves commonly become altered on crossing the shoaling bottom of
      the continental shelf in Santa Monica Bay, Calif. The alteration takes the form
      of internal swash (in which the lower isotherms reach farther landward than would
      be expected from their depth above the outer shelf or above deeper bottom) and of
      internal surf (that is, denoted by temperature inversions, isolated boluses of
      colder water at the bottom, and complex short wave-length variations of
      isotherms).

PMID- 16592106
TI  - Neutron diffraction structure of melampodin: its role in the reclassification of
      the germacranolides.
AB  - The precise crystal and molecular structure of melampodin, C(21)H(24)O(9), was
      determined from three-dimensional neutron diffraction data collected by counter
      techniques and phases by direct statistical methods. Crystals are orthorhombic,
      P2(1)2(1)2(1), a = 8,990(9), b = 14.352(14), c = 16.294(16) A, V = 2102 A(3),
      d(calc.) = 1.328 g.cm(-3), Z = 4 molecules per unit cell. The structural model
      was refined by full matrix least-squares of 2303 observed independent
      reflections, with all 54 atoms treated anisotropically, to R(F) = 5.0%. Hydrogen
      bonds link melampodin molecules together in the solid state. The conformation of
      the cyclodeca-1,5-diene ring is such that one intraannular hydrogen atom
      interacts strongly with one double bond, but there is little or no transannular
      interaction between double bonds. Strain in the ten-membered ring and in the
      trans-fused lactone ring is discussed, as are chemical implications of the
      unsymmetric epoxide in the epoxyangelic acid side chain. The previously suggested
      reclassification of germacranolide sesquiterpene lactones into four subgroups is
      supported, and a new convention for configurational representations of the four
      subgroups is proposed.

PMID- 16592107
TI  - Resonance Raman studies of the electronic state of oxygen in hemerythrin.
AB  - Excitation of oxyhemerythrin with radiation within the envelope of its strong
      oxygen --> iron chargetransfer band generates two Raman frequencies, at 844 cm(
      1) and 500 cm(-1). These are assigned to O-O and Fe-O stretching modes.
      Confirmation of these assignments is provided by the observed shifts in frequency
      when (16)O(2) is substituted by (18)O(2) as ligand. Comparison of the position of
      the 844-cm(-1) band with band positions of small molecules of known oxidation
      state clearly establishes that the bound oxygen is in an O(2) (2-), peroxide
      type, electronic state.

PMID- 16592108
TI  - Disulfide bond dihedral angles from Raman spectroscopy.
AB  - Raman spectra of several compounds containing the CS-SC moiety were obtained (in
      the solid phase) from 450-800 cm(-1) to investigate the S-S and C-S stretching
      behavior. The S-S stretching frequency varied linearly with the CS-SC dihedral
      angle (obtained from either x-ray or neutron diffraction or ultraviolet
      absorption) for compounds whose CC-SS dihedral angles were not very different.
      The ratio of the intensities of the S-S and C-S stretching bands exhibited no
      recognizable correlation with either the CS-SC dihedral angle or the CSS bond
      angle, probably because this ratio is sensitive to the crystalline environment.
      The linear dependence of the S-S stretching frequency on dihedral angle leads to
      a dihedral angle for the plant hormone, malformin A, that is in excellent
      agreement with that estimated from the longest wavelength CS-SC ultraviolet
      absorption band.

PMID- 16592109
TI  - Setae of the First Antennae of the Copepod Cyclops scutifer (Sars): Their
      Structure and Importance.
AB  - Ultrastructural studies of the setae of the first antennae of Cyclops scutifer
      (Sars) have revealed their sensory function. The setae are the extension of
      modified ciliary structures which function as mechanoreceptors. The setae
      apparently act to detect gravitational and inertial forces. This is of particular
      importance in sensing disturbances generated by prey or predators.

PMID- 16592110
TI  - Habituation of tobacco pith cells for factors promoting cell division is
      heritable and potentially reversible.
AB  - A type of heritable cellular change, known as habituation, occurs spontaneously
      in plant tissue and cell culture. This phenomenon is characterized by a newly
      acquired capacity of plant cells to produce growth regulatory substances. Using
      cloned lines of tobacco pith parenchyma cells, we demonstrated that a newly
      acquired character, in this instance an ability to produce a factor promoting
      cell division, is inherited by individual cells, that it persists for long
      periods of time, but that it is regularly reversible under completely defined
      experimental conditions. Evidence is presented that suggests that habituation
      results from heritable alterations in the pattern of gene expression and that it
      can, therefore, be used as a model for study of cell differentiation. The
      significance of these findings to the tumor problem is discussed.

PMID- 16592111
TI  - Sodium dynamics in a northern ecosystem.
AB  - Analyses of terrestrial sources of sodium and estimates of the sodium requirement
      of moose (Alces alces) on Isle Royale, Lake Superior, suggest that availability
      of the element controls the moose population. The terrestrial vegetation is very
      poor in the element, but, as elsewhere, submerged and floating leaved water
      plants are relatively rich. Consumption of such plants in summer would provide an
      adequate source, if the animal can store the element. The fairly high sodium
      contents of freshwater vegetation have been little appreciated. In general,
      sodium concentration in water-plants, unlike that of potassium, is not correlated
      with chloride but the latter is ordinarily in excess of the sodium, so that
      uptake of the latter implies an equivalent supply of NaCl.

PMID- 16592112
TI  - Biosynthesis of the Juvenile Hormones of Manduca sexta: Labeling Pattern from
      Mevalonate, Propionate, and Acetate.
AB  - Using organ culture, high-resolution liquid chromatography, and microchemical
      techniques, we demonstrated the efficient incorporation in vitro of several
      radiolabeled precursors into the two juvenile hormones of Manduca sexta. JH II, a
      homosesquiterpene hormone, reported from M. sexta as well as several other
      insects, incorporates radiolabel from acetate, mevalonate, and propionate. JH
      III, a sesquiterpene hormone recently reported as a natural product of M. sexta,
      incorporates label from acetate and mevalonate, but not from propionate. Based on
      the position of the labeled atoms in the precursors and upon the position of
      incorporation obtained from label-distribution data, a scheme for juvenile
      hormone biosynthesis is advanced.

PMID- 16592113
TI  - Oxidation-reduction potentials of bound iron-sulfur proteins of photosystem I.
AB  - Digitonin - fractionated photosystem - I subchloroplasts were titrated
      potentiometrically between -450 and -610 mV at pH 10. Examination of the titrated
      subchloroplasts by low-temperature (13 degrees K) electron paramagnetic resonance
      spectroscopy revealed resonances centered at values of 2.05, 1.94, 1.92, 1.89,
      and 1.86 on the g-factor scale. The peak heights depended on the potentials at
      which the chloroplasts were poised. The resonances of at least three iron-sulfur
      centers can be recognized: one with lines at g = 2.05 and 1.94; one with lines at
      g = 2.05, 1.92, and 1.89; and one for which only a line at g = 1.86 has been
      resolved. The midpoint potentials of the iron-sulfur species fall into two
      distinctly separate regions: the titration profile of the g = 1.94 signal, the
      first segment of the g = 2.05 plot, and the rise phase of the g = 1.86 signal had
      a value of -530 +/- 5 mV; the upper segment of the g = 2.05 plot, the decrease
      phase of the g = 1.86 signal, and the g = 1.89 profile had a midpoint potential
      estimated to be [unk] -580 mV. The oxidation-reduction reaction of each of the
      bound iron-sulfur species, as represented by the changes of the electron
      paramagnetic resonance spectra, was reversible and apparently involved a two
      electron change.Titration at pH 9 could only be carried to -560 mV, and
      essentially only the first half of the titration behavior as found at pH 10 was
      seen. At any given potential more positive than -560 mV, the part of the iron
      sulfur protein that was not reduced electrochemically could be reduced
      photochemically, but only to the maximum extent reduced electrochemically at -560
      mV. Whereas, chloroplasts illuminated at room temperature and then frozen while
      still being illuminated developed a signal similar to that produced by
      electrochemical reduction at -610 mV, illumination at 77 degrees K did not bring
      about photoreduction beyond that accomplished electrochemically at about -560
      mV.Dithionite alone in the dark and under anaerobic conditions brought about a
      partial reduction to the extent of the first electrochemical reduction step.
      Dithionite plus illumination at room temperature or dithionite plus methyl
      viologen in the dark produced the maximum signal. Electron paramagnetic resonance
      spectra due to either light or electrochemically reduced iron-sulfur proteins
      showed no detectable decay for at least 3 days when samples were stored in the
      dark at 77 degrees K.

PMID- 16592114
TI  - A new elastic potential function for rubbery materials.
AB  - A new four-parameter elastic potential function is proposed which represents data
      on the elastic deformation of rubbery materials with the same parameters in
      various deformation fields up to break.

PMID- 16592115
TI  - High-pressure spectral studies of mixed valence compounds of antimony.
AB  - In Cs(2)SbCl(6) and related compounds antimony appears as Sb(III) and Sb(V) in
      alternate halide octahedra. The optical spectrum contains "mixed valence" peaks
      assigned to Sb(III) --> Sb(V) transfer near 18 and 27 kK (cm(-1)). In addition
      there is a peak near 31 kK assigned to an internal transition on Sb(III) and one
      near 37 kK assigned to Sb(V), mixed with the absorption edge of the crystal. The
      mixed valence peaks shift strongly to lower energy with pressure (about 5 kK in
      120 kbar), and decrease rapidly in integrated intensity, as does the Sb(III) peak
      near 31 kK. A new peak appears near 33-34 kK, tentatively assigned to Sb(IV). The
      ground state apparently transforms from Sb(III)-Sb(V) to Sb(IV)-Sb(IV) at high
      pressure. Similar behavior is observed for Cs(2)Sb(0.3)Sn(0.7)Cl(6) and
      (CH(3)CH(2)NH(3))(2)Sb(0.5)Sn(0.5)Cl(6).

PMID- 16592116
TI  - Auxin-induced hydrogen ion excretion from Avena coleoptiles.
AB  - Avena coleoptiles excrete hydrogen ions in response to the hormone auxin. Both
      auxin-induced cell elongation and hydrogen ion excretion occur after only a short
      lag, and both are prevented by either carbonyl cyanide m-chlorophenylhydrazone or
      cycloheximide. These results support the idea that hydrogen ions act as a second
      messenger in auxin-induced cell elongation and can be the wall-loosening factor.

PMID- 16592117
TI  - Role of allophycocyanin as light-harvesting pigment in cyanobacteria.
AB  - Photosynthetic action spectra of several cyanobacteria show a peak at about 650
      nm, the height of which is correlated with allophycocyanin content in the strains
      examined. Allophycocyanin harvests light more efficiently than do phycocyanin and
      phycoerythrin. The contribution of chlorophyll a absorption to photosynthetic
      activity is barely detectable in cells of normal pigment composition. Chlorophyll
      a becomes the major light-harvesting pigment in cells that have been
      physiologically depleted of phycobiliproteins.

PMID- 16592118
TI  - Magnetofluid-dynamic spectrum and low shear stability.
AB  - For a perfectly conducting, cylindrical plasma equilibrium ("screw-pinch"), the
      spectrum contains four distinct continua, three of which can extend to the
      origin. This implies the existence of irreversible damping and heating in the
      nondissipative model. The continuum becomes (Suydam) unstable by instantly
      shedding an infinite number of point eigenvalues. More generally, any local
      instability implies an infinity of unstable eigenvalues. Spectral analysis of a
      new class of low shear, semilocal unstable modes provides a connection between
      Suydam modes, found only in sheared systems, and interchanges, found only in
      closed line (shearless) systems, and gives rise to the concept of an effective
      marginal stability threshold. Study of the spectrum should also provide a unified
      picture of many other plasma phenomena.

PMID- 16592119
TI  - Light-induced phase shifts of circadian leaf movements of phaseolus: comparison
      with the effects of potassium and of ethyl alcohol.
AB  - Leaves of Phaseolus coccineus were exposed to high concentrations of KCl (0.1-0.3
      M) for periods of 4-5 hr, or to ethyl alcohol (5-30%) for periods of 2 hr. The
      treatment started at various phases of the free-running circadian rhythm in
      continuous light. Whereas the K(+) pulses induced only advance phase shifts,
      i.e., shortening of the periods, the alcohol pulses caused stronger advances and
      also slight delays, i.e., lengthening of the periods. These delays became
      stronger with lower concentrations of alcohol (1.7%) applied for a longer time.
      The lengthening effect by alcohol supplied continuously depends on the intensity
      of light. The rather high intensity of 3500 lux, resulting in very long free
      running periods of about 29 hr, inhibits a further strong lengthening by alcohol.
      The phases reacting with advances to K(+) and to alcohol are about the same
      phases that respond to light pulses with advances. The advances are reached at
      earlier phases of the circadian cycle when the concentration of alcohol or the
      strength of the light pulse is increased. The phases that respond with advances
      are those which, according to earlier publications, are within the energy
      independent part of the cycle. The phases responding with delays belong to the
      energy-requiring part of the cycle. Consequently, it is suggested that advances
      are due to accelerated membrane depolarization and delays are due to stabilizing
      effects on membranes.

PMID- 16592120
TI  - Stereochemical Correspondence among Chemically Disparate Systems: Spirocyclic
      Phosphoranes, Diarylmethanes, and Cognates.
AB  - Certain chemical systems which differ greatly in many of their chemical
      properties may nevertheless exhibit stereochemically isomorphic behavior, i.e.,
      they may be stereochemically correspondent. Two such systems are spirocyclic
      pentacoordinate molecules and molecules of the type Ar(2)ZX. The consequences of
      stereochemical correspondence between these two systems are explored in depth.

PMID- 16592121
TI  - Spectral properties of an oxygenated luciferase-flavin intermediate isolated by
      low-temperature chromatography.
AB  - Bacterial luciferase catalyzes the oxidation of reduced flavin mononucleotide by
      molecular oxygen; long-chain aldehyde is required for light emission. At 20
      degrees the bioluminescence has a lifetime of tens of seconds, while excess
      reduced flavin is removed by way of nonenzymatic autoxidation in less than a
      second. This observation indicates the existence of a long-lived enzyme
      intermediate, which has been postulated to be a peroxide of the enzyme-bound
      reduced flavin. This intermediate was isolated and studied at low temperature (
      20 degrees ), where it has a lifetime measured in days. It has an absorption with
      a single band peaking at 372 nm, and fluorescence emission centered at about 485
      nm, which might be expected for the postulated flavin peroxide. Upon conversion
      to product, flavin mononucleotide-like absorption and fluorescence appear,
      supporting the postulate that flavin turns over in the reaction. Upon injection
      into buffer at 20 degrees with added aldehyde, bioluminescence occurs. Based on a
      stoichiometry of one flavin per luciferase molecule, the specific activity of the
      intermediate is equal to that of pure luciferase.

PMID- 16592122
TI  - Hybridization of leucyl-transfer ribonucleic Acid isoacceptors from green leaves
      with nuclear and chloroplast deoxyribonucleic Acid.
AB  - Chromatographically distinct isoacceptors of leucyl-tRNA from mature bean leaves
      were all observed to hybridize with bean chloroplast and nuclear DNA in a ratio
      similar to that exhibited by the unfractionated leucyl-tRNA. Under the same
      hybridization conditions, maize tRNA failed to form a stable hybrid with bean
      DNA, and levels of hybridization between bean-leaf leucyl-tRNA and nuclear or
      chloroplast DNAs from tobacco and maize were relatively small.

PMID- 16592123
TI  - Asymptotics of some relativistic markov processes.
AB  - Markov processes in special-relativistic position-velocity phase space are proved
      to have converging velocities as t --> + infinity under some mild assumptions on
      transition probabilities. This offers a possible mechanism to explain the
      recession of galaxies.

PMID- 16592124
TI  - 3-bromo-2-butanone 1,4-bisphosphate as an affinity label for ribulosebisphosphate
      carboxylase.
AB  - 3-Bromo-2-butanone 1,4-bisphosphate has been synthesized in an attempt to find a
      reactive analog of ribulose 1,5-bisphosphate for labeling the active site of
      ribulosebisphosphate carboxylase (EC 4.1.1.39). The reagent irreversibly
      inactivates the carboxylase from spinach, and several observations suggest that
      the inactivation results from modification of an active-site residue: (1)
      Ribulose 1,5-bisphosphate protects against inactivation. (2) The extent of
      reagent incorporation shows that modification of one residue per catalytic site
      can account for the inactivation. (3) Comparisons of autoradiograms of peptide
      maps prepared from carboxylase treated with the (32)P-labeled reagent in the
      absence and presence of substrate indicate that inactivation results from a
      fairly selective modification. (4) Although the reagent's greatest inherent
      reactivity is toward sulfhydryl groups, inactivation of the enzyme is due to
      alteration of an amino-acid residue other than cysteine.

PMID- 16592125
TI  - Oxaloacetate as the hill oxidant in mesophyll cells of plants possessing the c(4)
      dicarboxylic Acid cycle of leaf photosynthesis.
AB  - Isolated mesophyll cells from leaves of plants that use the C(4) dicarboxylic
      acid pathway of CO(2) fixation have been used to demonstrate that oxaloacetic
      acid reduction to malic acid is coupled to the photochemical evolution of oxygen
      through the presumed production of NADPH. The major acid-stable product of light
      dependent CO(2) fixation is shown to be malic acid. In the presence of
      phosphoenolpyruvate and bicarbonate the stoichiometry of CO(2) fixation into acid
      stable products to O(2) evolution is shown to be near 1.0. Thus oxaloacetic acid
      acts directly as the Hill oxidant in mesophyll cell chloroplasts. The experiments
      are taken as a firm demonstration that the C(4) dicarboxylic acid cycle of
      photosynthesis is the major pathway for the fixation of CO(2) in mesophyll cells
      of plants having this pathway.

PMID- 16592126
TI  - Isolation of cis-Zeatin from Corynebacterium fascians Cultures.
AB  - Three cytokinin-active constituents have been isolated from the culture medium of
      Corynebacterium fascians, a plant pathogen causing fasciation. One constituent is
      now identified as cis-zeatin [6-(4-hydroxy-3-methyl-cis-2-butenylamino)purine].
      It represents the first unequivocal demonstration of the production of a zeatin
      isomer by a bacterial species. Another constituent was identified earlier as 6-(3
      methyl-2-butenyl-amino)purine. The third constituent, distinct, on Sephadex LH-20
      column chromatography, from the above two and their ribosides, has not yet been
      identified.

PMID- 16592127
TI  - Binding properties in vitro of phytochrome to a membrane fraction.
AB  - Brief irradiation of a buffer extract of dark-grown zucchini squash seedlings
      with red light results in the binding of the far-red-absorbing form of
      phytochrome to a particulate fraction. A low concentration of magnesium (0.1 mM)
      permits partial far-red reversal of the binding. A higher concentration (10 mM)
      yields actually enhanced binding after the far-red treatment. Both magnesium and
      calcium have a strong effect on the vesicularization of the phytochrome-binding
      particles and on their aggregation into readily sedimentable complexes. At
      concentrations above 10 mM, binding of the far-red-absorbing form of phytochrome
      is inhibited. These effects were not observed with sodium or potassium.
      Increasing the H(+) concentration led to increased binding of the far-red
      absorbing form. This form of phytochrome bound at pH 6.5 and 10 mM magnesium is
      released if either the pH is raised to 8.0 or the magnesium concentration is
      raised to 50 mM. These properties suggest a new method for phytochrome
      purification.

PMID- 16592128
TI  - Barrier Height for the Exchange Reaction F + HF --> FH + F.
AB  - There exists a body of conflicting data as to the existence or nonexistence of
      FHF, ClHCl, BrHBr, and IHI as chemically bound molecular species. Ab initio
      quantum mechanical electronic structure calculations are presented which predict
      linear symmetric FHF to be unstable. The barrier height for the F + HF exchange
      reaction is suggested to be no less than 18 kcal/mol, much larger than expected
      either intuitively or on the basis of certain experiments on related systems. The
      expected reliability of the calculations is based upon comparable results for
      diatomic molecules and the F + H(2) and H + F(2) potential energy surfaces.

PMID- 16592129
TI  - A new general estimate of the rate of convergence in the central limit theorem in
      R.
AB  - A general theorem is proved which gives an estimate of the rate of convergence on
      convex sets in the multidimensional central limit theorem for identically
      distributed summands. The estimate depends on the distance of the boundary of the
      convex set from the origin (the larger the distance, the better the estimate).
      The estimate makes sense under minimal requirements on the moments. Furthermore,
      the dependence on the distribution of a summand in it is in terms of pseudo
      moment type quantities which may be small even if the moments are large.

PMID- 16592130
TI  - Low Temperature Electronic Absorption Spectra of Oxidized and Reduced Spinach
      Ferredoxins. Evidence for Nonequivalent Iron(III) Sites.
AB  - The electronic absorption spectra of oxidized and reduced spinach ferredoxins
      have been measured between 1200 and 600 nm at low temperature in D(2)O/ethylene
      glycol glasses. Relatively weak absorption bands are observed at 720, 820, and
      920 nm in oxidized ferredoxin, and at 652, 820, and 920 nm in reduced ferredoxin.
      The spectral results show that the two Fe(III) centers in oxidized ferredoxin are
      not equivalent, and that the 820- and 920-nm bands are associated with the
      nonreducible site. Assignment of the reducible site as tetrahedral Fe(III) is
      indicated. The 720-nm (13.9 kcm(-1)) band in oxidized ferredoxin is attributed to
      an intensity-enhanced (6)A(1) --> (4)T(1)d-d transition, whereas the 652-nm (15.3
      kcm(-1)) feature of reduced ferredoxin could be due either to (5)E --> (3)T(1) in
      tetrahedral Fe(II)S(4) or an Fe(II) --> Fe(III) intervalence excitation.

PMID- 16592131
TI  - The selectivity principle and the question of the bridged structure of the 2
      norborynyl cation.
AB  - Low exo/endo rate ratios in the solvolysis of certain norbornyl derivatives have
      been attributed to the involvement of classical (unbridged) 2-norbornyl cations.
      Consequently, the high exo/endo rate ratio in the parent system, 2-norbornyl
      arenesulfonates, has been interpreted as involving rate enhancement in the exo
      isomer arising from sigma-participation. It is pointed out that this treatment
      involves neglect of the Selectivity Principle. Taking the relative reactivity of
      cyclopentyl to cyclohexyl as a representative test system, it is pointed out that
      those reactions which reveal low exo/endo rate ratios in norbornyI also reveal
      low cyclopentyl/cyclohexyl rate ratios. It is proposed that the low exo/endo rate
      ratios in norbornyl, observed in the above reactions, arise from the low
      selectivities of the test reactions. Consequently, the results cannot be utilized
      to support the argument that low exo/endo rate ratios reflect the absence of
      sigma-participation and high exo/endo rate ratios reflect the presence of sigma
      participation.

PMID- 16592132
TI  - Qualms regarding the range of validity of the glansdorff-prigogine criterion for
      stability of non-equilibrium States.
AB  - Doubt is raised concerning the range of validity of a stability criterion for non
      equilibrium states which has been proposed by Glansdorff and Prigogine. In the
      case of a particular autocatalytic reaction, the stability analysis presented by
      Glansdorff and Prigogine, and by Eigen and by Katchalsky in their reviews of this
      problem, does not agree with our analysis, which is based upon exact solution of
      the relevant rate equations. We also find disagreement between the analysis based
      upon the Glansdorff-Prigogine criterion and our analysis of a second example
      which involves non-equilibrium steady states. The situation is quite delicate
      because seemingly innocent approximations (e.g., the use of specialized
      conditions in the autocatalytic reaction X + Y right arrow over left arrow 2X
      discussed in the sequel) may lead to the impression that the scope of validity of
      the criterion is wider than it actually is. By considering the stability of the
      equilibrium state, we conclude that the second differential of the entropy, which
      is at the heart of the Glansdorff-Prigogine criterion, is likely to be relevant
      for stability questions close to equilibrium only.

PMID- 16592133
TI  - The thermodynamic stability theory of non-equilibrium States.
AB  - The paper by J. Keizer and R. F. Fox entitled "Qualms Regarding the Range of
      Validity of the Glansdorff-Prigogine Criterion for Stability of Non-Equilibrium
      States" [(1974) Proc. Nat. Acad. Sci. USA 71, 192-196.] is shown to be based on a
      misunderstanding of the work of the Brussels group. In order to avoid further
      confusion, we summarize the formulation of the stability criterion in accordance
      with our published work. The differences with the presentation by Keizer and Fox
      are pointed out and it is shown that, when correctly applied, our approach does
      not lead to any contradiction with other methods available for studying
      stability.

PMID- 16592134
TI  - Effect of chemical substitution on absorption spectra and magnetic circular
      dichroism of molecules in dense media.
AB  - The purpose of this paper has been to study the effect of chemical substitution
      on the magnetic circular dichroism and absorption spectra for the parent molecule
      which has the C(2v) symmetry. Four electronic transitions, A(1) --> A(1), A(1) -
      > B(1), A(1) --> B(2), and A(1) --> A(2) have been considered. In each case, the
      intensity changes in magnetic circular dichroism and absorption spectra due to
      substitution have been expressed in terms of number of substituents and positions
      of substitution.

PMID- 16592135
TI  - Atmospheric corrosion.
AB  - A model of electrolytic corrosion is developed. It is shown that electrically
      conducting channels threading through the oxide layer and connecting anodic and
      cathodic areas, obey the equation for a reactant being catalyzed by its product.
      The resulting autocatalytic equation is compared with available experimental data
      and found to be widely applicable and capable of unifying many experimental
      observations.

PMID- 16592136
TI  - The Crystal and Molecular Structure of Ethyl Chlorophyllide a.2H(2)O and Its
      Relationship to the Structure and Aggregation of Chlorophyll a.
AB  - Determination of the crystal structure of ethyl chlorophyllide a.2H(2)O by single
      crystal x-ray diffraction techniques has provided the first detailed molecular
      structural data available for a magnesium-containing derivative of chlorophyll.
      At the same time the aggregation observed in this structure serves as the basis
      for a model of chlorophyll aggregation in vitro and in vivo. The magnesium atom
      in ethyl chlorophyllide is displaced 0.4 A from the plane of the chlorin ring in
      the same direction as the methyl ester substituent. A water molecule occupies the
      fifth coordination site. A second water molecule is hydrogen bonded to the
      coordinated water molecule and also to the carbonyl oxygen atom of the methyl
      ester. Hydrogen bonds between the water molecules and carbonyl oxygen atoms link
      the chlorophyllide molecules into a two-dimensional aggregate of crosslinked one
      dimensional polymers. The relationship of this aggregate to aggregates of
      chlorophyll both in vitro and in vivo is discussed, as is the efficiency of
      exciton transport within the polymer.

PMID- 16592137
TI  - Ribosyl-trans-Zeatin, A Major Cytokinin Produced by Crown Gall Tumor Tissue.
AB  - A cell division factor in crystalline form has been isolated from ethanolic
      extracts of cultured Vinca rosea L. crown gall tumor tissue. The crystalline
      material shows the melting point, mass spectrum, ultraviolet-light absorbancy
      spectra, solubilities, chromatographic migration values, ion-exchange behavior,
      and growth activities expected of ribosyl-trans-zeatin, that is, 6-(4-hydroxyl-3
      methyl-trans-2-butenylamino)-9-beta-D- ribofuranosylpurine. This compound, which
      appears to be a major cell-division factor in the extracts, has also been
      crystallized from liquid media in which the tumor tissue had been growing and
      apparently was the only active compound in such media.

PMID- 16592138
TI  - Migration and species diversity in the tropics.
AB  - If the young of a dominant species are subjected to disproportionately heavy
      predation, this, together with a limitation on food, can promote a high species
      diversity. This is seen among tropical birds, which are simultaneously exposed to
      both conditions to a far greater degree than are Temperate Zone species.
      Migration to the Temperate Zones during the spring provides a release from these
      restraints, while also precluding breeding in the Tropics.

PMID- 16592139
TI  - Asymptotic of the Green's Function of a Riemannian Manifold and Ito's Stochastic
      Integrals.
AB  - Quantitative estimates are obtained by comparison with ordinary differential
      equations associated to a subharmonic exhaustion function q. We associate with q
      a ratio a, which can be considered as the heat flow in an intrinsic time, and the
      sup and the inf of a, namely a(+) and a(-), on the level hypersurfaces of q. Then
      a(+) and a(-) define heat flows on the real line. Comparison between the heat
      flow on the manifold and heat flows on the line are obtained by stochastic
      integrals.

PMID- 16592140
TI  - Poly(A) polymerase and poly(g) polymerase in wheat chloroplasts.
AB  - Extracts of wheat chloroplasts contain a poly(A) polymerase which can polymerize
      AMP residues from ATP onto an RNA primer. Whole extracts of wheat leaves also
      contain another poly(A) polymerase which is present in much larger amount and is
      probably derived from the nuclei. Both polymerases can utilize as primer poly(A),
      poly(C), transfer RNA, and ribosomal RNA, but only the chloroplast polymerase can
      utilize poly(U) and poly(G). Both enzymes have a specific requirement for ATP.
      Extracts of wheat chloroplasts contain, in addition to the poly(A) polymerase, a
      poly(G) polymerase which can polymerize GMP residues from GTP onto primers such
      as poly(G), poly(A), or ribosomal RNA. The poly(G) polymerase cannot utilize ATP
      but can slowly polymerize CMP from CTP. When the two chloroplast polymerases are
      present together in an in vitro incubation with ATP plus GTP and poly(A), the
      polymerization product is a mixed poly(A,G) tract.

PMID- 16592141
TI  - The Juvenile Hormone Binding Protein in the Hemolymph of Manduca sexta Johannson
      (Lepidoptera: Sphingidae).
AB  - C(18):juvenile hormone is quite soluble in water, yielding a monomeric solution
      greater than 10(-5) M. In vivo injection or addition of aqueous juvenile hormone
      to the hemolymph in vitro shows the complexation of juvenile hormone to a
      protein, as demonstrated by gel permeation chromatography and disc-gel
      electrophoresis. The protein has an apparent molecular weight of 3.4 x 10(4) and
      is present in the hemolymph at a concentration in the micromolar range. The
      binding of the hormone to the protein can be described as a simple thermodynamic
      equilibrium with a dissociation constant of 3 x 10(-7) M, and the protein has a
      much higher affinity for the hormone than for the hydrolysis products.

PMID- 16592142
TI  - Detection and quantitation of octopine in normal plant tissue and in crown gall
      tumors.
AB  - Octopine has been detected in normal tobacco leaf and stem tissue, normal
      sunflower stem tissue, pinto bean leaves, and normal tobacco callus tissue in
      culture. Octopine was identified in extracts by means of electrophoresis and
      chromatography in several solvent systems. Tobacco and sunflower tumor lines
      induced by various strains of Agrobacterium tumefaciens were found to contain
      from 1 to 240 times as much octopine as the normal plant tissues examined.
      Several strains of A. tumefaciens produce undifferentiated tobacco tumors
      containing high levels of octopine, but produce undifferentiated sunflower tumors
      containing normal levels of octopine and high levels of arginine. Further, strain
      CGIC of A. tumefaciens produces in tobacco an undifferentiated tumor which
      contains high levels of octopine and a teratoma which contains normal levels of
      octopine. This evidence shows that there is no consistent relationship between
      the causative strain of A. tumefaciens and the octopine content of the resulting
      crown gall tumor.

PMID- 16592143
TI  - Beginnings of village-farming communities in southeastern Turkey-1972.
AB  - The mound known as Cayonu Tepesi (38 degrees 16' N; 39 degrees 43' E) in
      southeastern Turkey is one of the increasing number of early village sites which,
      since World War II, have been excavated archeologically in greater southwestern
      Asia. The evidence recovered in the autumn 1972 campaign of the Joint Istanbul
      Chicago Prehistoric Project is briefly described, with particular attention to
      Cayonu's architectural remains, which are most remarkable, considering the site's
      date of about 7000 B.C. There was evidence of domesticated food plants from the
      beginning but animal domesticates were not present (save the dog) until later in
      the major prehistoric phase of occupation.

PMID- 16592144
TI  - Were workers of eusocial hymenoptera initially altruistic or oppressed?
AB  - Studies of a primitively eusocial halictid bee, Lasioglossum zephyrum, strongly
      suggest that a major factor in originating a worker caste is selection at the
      individual level for queens that control associated adult females. Even in this
      scarcely social form, the queen inhibits other adult females from becoming
      queens, perhaps by her high level of activity and frequent nudging in the nest.
      Queens are behaviorally less varied than workers and show specialization,
      particularly in frequency of nudging (which is concentrated on the worker with
      largest ovaries) and of backing. Backing draws workers, especially those with
      slender ovaries, down to lower parts of the burrows where the stimuli for cell
      construction and provisioning probably operate. Eating of worker-laid eggs by
      queens was also noted. In spite of the suggestion that queens have evolved to
      control their workers rather than that workers have evolved to help their queens,
      both may well have occurred, for these processes are not mutually exclusive;
      moreover, social attributes mutually beneficial to both castes no doubt have
      arisen.

PMID- 16592145
TI  - A variant of special relativity and long-distance astronomy.
AB  - THE REDSHIFT, MICROWAVE BACKGROUND, AND OTHER OBSERVABLE ASTRONOMICAL FEATURES
      ARE DEDUCED FROM TWO THEORETICAL ASSUMPTIONS: (1) global space-time is a certain
      variant of Minkowski space, locally indistinguishable in causality and covariance
      features but globally admitting the full conformal group as symmetries although
      having a spherical space component; (2) the true energy operator corresponds to a
      certain generator of this group which is not globally scale-covariant, whereas
      laboratory frequency measurements are inevitably such and correspond to the
      conventional energy operator [unk]/i[unk]/[unk]t.

PMID- 16592146
TI  - The Secretion of alpha-Ecdysone by the Prothoracic Glands of Manduca sexta In
      Vitro.
AB  - Prothoracic glands of tobacco hornworm larvae cultured in vitro secrete into the
      culture medium a substance which was active in ecdysone bioassays and determined
      to be ecdysone-like by radioimmunoassay. The prothoracic glands appear to be the
      sole source of this substance. The material was identified as alpha-ecdysone by
      thin-layer, gas-liquid, and high-resolution liquid chromatography and mass
      spectrometry. No other active moulting principles were present in the medium. It
      appears that the prothoracic gland secretes a prohormone, alpha-ecdysone, which
      is subsequently converted into the active moulting hormone, beta-ecdysone, in
      other insect tissues.

PMID- 16592147
TI  - Carotenoid transformations in the chloroplast envelope.
AB  - The envelope of the spinach chloroplast is a yellow membrane system with a unique
      carotenoid composition. Envelopes prepared from dark-treated leaves had a
      violaxanthin content up to 3.5 times the lutein plus zeaxanthin content, whereas
      in chloroplast envelopes from illuminated leaves this ratio was only 0.75. Light
      catalyzed changes in violaxanthin content also occurred in the thylakoid
      fraction.The role of this reversible light-catalyzed de-epoxidation of
      violaxanthin in the function of the envelope of the chloroplast is discussed.

PMID- 16592148
TI  - Four peroxidase Loci in red-fruited tomato species: genetics and geographic
      distribution.
AB  - The banding patterns of certain anodal peroxidase variants of red-fruited tomato
      species are governed by alleles at four loci-two alleles per locus. Alleles at
      three loci code for modified enzyme migration patterns and are codominant in
      heterozygotes; those at the fourth locus code for presence or absence of a band.
      No evidence of linkage was detected in preliminary tests between four of the six
      possible combinations of loci. All variant alleles-i.e., those not represented in
      the standard genotype of Lycopersicon esculentum-exist in the wild L.
      pimpinellifolium from coastal Peru; all but Prx-3(n) are also known in L.
      esculentum from the sympatric region but are rare or absent elsewhere. Between
      the distributions of alleles of Prx-1 and those of Ge, the gamete-eliminator
      locus, a significant association exists, which probably does not owe to genetic
      linkage. The tendency of alleles of Prx loci, as well as those of cm, Ge, h, and
      Od, to be shared between wild and cultivated taxa in the sympatric region but
      seldom elsewhere, in addition to published correlated evidence, suggests that the
      wild alleles tend to substitute in cultivated forms as a result of introgression.
      In respect to the number of common alleles, cultivated tomatoes more closely
      resemble the wild L. esculentum var. cerasiforme than L. pimpinellifolium.

PMID- 16592149
TI  - Olfactory Basis of Homing Behavior in the Giant Garden Slug, Limax maximus.
AB  - Time lapse photography of slugs living in an experimental enclosure shows that
      these animals can return to a homesite from over 90 cm by a direct route. Slime
      trail following and vision are not involved in this behavior. In the presence of
      a low velocity wind, homing occurs upwind. Surgical disconnection of the
      presumptive olfactory apparatus (digitate ganglion) from the central nervous
      system eliminates homing. Neurophysiological recordings from the receptor surface
      associated with the digitate ganglion and the olfactory nerve demonstrate the
      olfactory function of the digitate ganglion. The olfactory acuity and capacity
      for directed locomotion via olfactory cues are also relevant to studies of slug
      feeding behavior, ecology, and learning ability.

PMID- 16592150
TI  - The cation radicals of free base and zinc bacteriochlorin, bacteriochlorophyll,
      and bacteriopheophytin.
AB  - One-electron oxidation of zinc tetraphenylbacteriochlorin and its metal-free base
      yielded stable cation radicals. Electron spin resonance hyperfine splittings were
      assigned by selective deuterations. These results indicate that the protons of
      the saturated rings of the bacteriochlorins carry large spin densities, in accord
      with molecular orbital calculations. Comparison in vitro of the optical spectra
      of bacteriochlorins and their cation radicals with those of bacteriochlorophyll
      show close correspondence and suggest that the electron spin resonance data from
      the former may also prove a guide to the biological molecule. The surprising
      similarity in properties between the radicals of free base and zinc
      bacteriochlorins is maintained in the chlorophylls: cation radicals of
      bacteriopheophytin and methyl pheophorbide (the free bases of bacteriochlorophyll
      and methyl chlorophyllide, respectively) exhibit electron spin resonance
      properties similar to those of their magnesium-containing derivatives. The
      possibility that metal-free chlorophylls participate in photosynthesis is
      discussed.

PMID- 16592151
TI  - At Least One-Third of Zeros of Riemann's Zeta-Function are on sigma = (1/2).
AB  - Starting from the derivative of the functional equation of the zeta-function, it
      is shown that at least one-third of the zeros of the zeta-function are on the
      line sigma = (1/2).

PMID- 16592152
TI  - A Simple Proof of Siegel's Theorem.
AB  - A brief and simple proof of Siegel's celebrated theorem that h(d) >> d(1/2
      [unk]), as d --> infinity, is given. Here h(d) denotes the class number of the
      quadratic field Q([unk]-d). Simple proofs that do not make use of algebraic
      number theory have been previously given by Estermann and Chowla.

PMID- 16592153
TI  - Solution by recursion of the N-body electrostatic schrodinger equation.
AB  - A generalized partial wave expansion of atomic wavefunctions has been shown to
      allow exact solution of the many-electron Schrodinger equation. This solution is
      constructed here by an algebraic recursion method, and several analytical
      properties of such wave-functions are easily obtained. Eigenstates of the atom
      correspond to such solutions which satisfy certain boundary conditions for
      infinite extension of the system. A method of locating these states is presented.

PMID- 16592154
TI  - Eulerian graphs and polynomial identities for sets of matrices.
AB  - Let the standard identity of degree m be given by [Formula: see text] Then the
      minimum standard identity is determined for the set of all n x n skew-symmetric
      matrices over a field of characteristic 0.

PMID- 16592155
TI  - Investigation of the composition and formation constant of molecular complexes.
AB  - It has been the purpose of the present paper to investigate and explore the
      conditions under which the linear relation between Delta/C(D) (0) and Delta in
      the Hanna-Ashbaugh-Foster-Fyfe equation for the evaluation of equilibrium
      constants holds, (C(D) (0) is initial concentration of a donor and Delta is the
      observed chemical shift relative to the chemical shift of the acceptor) to obtain
      the equation representing the exact linear relation between Delta/C(D) (0) and
      Delta, when the linear relation between Delta/C(D) (0) and Delta holds, and to
      discuss how to use the Job method in nuclear magnetic resonance measurements to
      determine the stoichiometry of molecular complexes. We have found that the
      conventional belief that C(D) (0) should always be chosen to be much greater than
      C(A) (0) (initial concentration of acceptor) is not necessarily always true and
      the exact linear relation between Delta/C(D) (0) and Delta is represented by the
      equation Delta/C(D) (0) = K(1)Delta(0)/(1 + K(1)C(A) (0)) - K(1)Delta/(1 +
      K(1)C(A) (0))(2), where K(1) is the formation constant of the complex. It is
      shown that in the Job method of nuclear magnetic resonance measurements one has
      to plot DeltaC(A) (0) against the mole fraction, and the mole fraction at the
      maximum should give us the composition of the complex. Theoretical results have
      been verified experimentally on the weak interaction between naphthalene and
      methyl iodide.

PMID- 16592156
TI  - An invariant for certain operator algebras.
AB  - It is shown that the so-called principal function invariant, which is associated
      in a unitarily invariant way to operators with trace class self commutator TT(*) 
      T(*)T, is invariant under trace class perturbations of T and is an extension of
      the index of T-z to the whole plane. The connection of the principal function,
      under additional hypothesis, with the determination of the maximal ideal space of
      the C(*) algebra generated by T is discussed, and it is shown that the principal
      function, even when it takes noninteger values, plays a role in establishing the
      existence of invariant subspaces for T and in determining the point spectrum of
      T.

PMID- 16592157
TI  - Localized molecular orbital description of nitrogen lone pairs.
AB  - The Boys localization procedure is applied to several molecules possessing
      nitrogen lone pairs. The Boys structures show a tendency for the N lone pairs to
      participate in bonding to nearby electron sinks. For example, the Boys structure
      for planar formamide has two equivalent tau-bond orbitals between the carbonyl
      carbon and nitrogen atoms. The change in this description with variation of
      geometry at nitrogen is treated, and analogous Edmiston-Ruedenberg localizations
      on formamide are included for comparison.

PMID- 16592158
TI  - The psychological concept of "losing move" in a game of perfect information.
AB  - From a game-theoretic standpoint, in any two-person game of perfect information,
      each position is won, lost, or drawn, and a move is to be considered an error
      only when it transfers the game from a more favorable to a less favorable state.
      A psychological concept of error is quite different, in that it must take into
      account the fallibility of the players as information processing systems. This
      paper introduces a psychological concept of error in such games based on the
      distinction between "obvious" and "problematic" moves, and proposes a formalism
      for this concept that appears to capture, at least to a first approximation, the
      notion of "losing move" as that phrase is actually used by players in games like
      chess.

PMID- 16592159
TI  - Ambient pyrite in precambrian chert: new evidence and a theory.
AB  - Ambient pyrites of two distinct types were described from middle Precambrian
      rocks of the Lake Superior area. A new class of this phenomenon is here described
      from middle Precambrian chert from western Australia. The newly found ambient
      pyrites are quite minute and characteristically occur in groups forming a
      "starburst" pattern. All three types of ambient pyrite may be explained in terms
      of pressure solution initiated by gas evolution from organic material attached to
      the pyrite. Thermal degradation of the kerogen produces the gases which, due to
      the impermeability of the encompassing chert, build up the pressures necessary to
      initiate solution. Pyrite appendages bear a striking resemblance to micro
      organisms and, thus, constitute the smallest pseudofossils known.

PMID- 16592160
TI  - The derivation of ecological relationships from physical and chemical principles.
AB  - Organic reaction networks are formalized by representing chemical species as
      points in a space and representing reactions by connectivity rules. Using the
      generalized network, the behavior of the system is investigated under conditions
      of electronically exciting input and output to a thermal reservoir. Under steady
      state conditions the system undergoes material cycles of the type shown by the
      major ecological cycles. A consideration of the attractor nature of the
      equilibrium state of the system leads to the conclusion that the energetically
      lowest-lying molecules must be inputs into the material cycles. Certain general
      features of the ecological system are thus shown to follow from the physical and
      chemical properties of an organic reaction network.

PMID- 16592161
TI  - On some isospectral second order differential operators.
AB  - A method of exhibiting potentials which are uniquely determined by their spectra
      is discussed and illustrated in an example.

PMID- 16592162
TI  - A characterization of banach spaces containing L.
AB  - It is proved that a Banach space contains a subspace isomorphic to l(1) if (and
      only if) it has a bounded sequence with no weak-Cauchy subsequence. The proof
      yields that a sequence of subsets of a given set has a subsequence that is either
      convergent or Boolean independent.

PMID- 16592163
TI  - Temperature dependence of isotope ratios in tree rings.
AB  - The stable isotope ratios of carbon, oxygen, and hydrogen have been measured for
      a German oak in wood samples of roughly three years each, for the years 1712-1954
      A.D., and correlated with the existing weather records from England, Basel, and
      Geneva to evaluate the empirical temperature coefficients. Isotope ratios in a
      second official oak, measured for the years 1530-1800 A.D., show the cold
      temperatures of the Little Ice Age interspersed with warm intervals.

PMID- 16592164
TI  - K(pin)-Torsors and the Interpretation of "Triple" Cohomology.
AB  - A categorical, semi-simplicial interpretation theory for "triple" cohomology is
      outlined which uses the groups TORS(U) (n)[X;pi] of connected components of
      certain categories of K(pi,n)-torsors (higher dimensional generalizations of
      locally trivial principal fiber bundles) to interpret the cohomology groups,
      i.e., TORS(U) (n)[X;pi] [unk] H(n)(X;pi), n >/= 1.

PMID- 16592165
TI  - From knowledge to action: science and its uses.

PMID- 16592166
TI  - Entropy, dynamics, and molecular chaos.
AB  - With the help of simple probabilistic models of Kac and McKean, we discuss the
      meaning of the generalized expression for entropy that was recently introduced by
      our group and compare it with Boltzmann's expression. We emphasize the fact that
      Boltzmann's formulation in terms of the single particle distribution function,
      f(1), requires very restricted assumptions about the preparation of the system
      (chaos) and the nature of the collision mechanism (Markov processes).Our
      generalized [unk]-theorem, however, refers to the complete system; in general, it
      does not lead to an [unk]-theorem for the single particle distribution function,
      f(1). It is valid whatever the preparation of the system. In McKean's model,
      situations exist where it gives the correct behavior while the Boltzmann's
      expression for entropy becomes meaningless. In addition, in Kac's model, we show
      that correlations reach equilibrium more rapidly than f(1) and that there is an
      asymptotic regime where both formulations give the same result.

PMID- 16592167
TI  - The second law of thermodynamics in bioenergetics.
AB  - Bioenergetic processes are viewed as processes of free energy transduction. The
      free energies of both local equilibrium and fluctuation states are being
      considered. It is shown that the exchange of thermal energy with the surrounding
      medium, acting as a reservoir, does not violate the second law of thermodynamics
      within broad limits. There is sufficient latitude for proteins to carry out their
      function of transduction utilizing thermal energy in the process.

PMID- 16592168
TI  - The evaluation of configuration coordinate parameters from high pressure
      absorption and luminescence data.
AB  - A configuration coordinate model was previously developed for relating the
      energies involved in optical and thermal electron excitations between two states
      and the effect of pressure on these energies. In the course of this development,
      expressions were presented for hv(max), the optical absorption peak maximum, and
      (E((1/2)))(a) the peak half-width, as functions of pressure, and of the
      parameters defined in the model. The analysis was later extended to emission. We
      elaborate on the equations for the change of hv(max) and E((1/2)) with pressure
      and discuss some of the problems involved in evaluating and using peak half
      widths. Various combinations of absorption and emission data for evaluating the
      parameters describing the excitation are discussed and are compared for
      phenanthrene in various environments.

PMID- 16592169
TI  - Some new asymptotic fixed point theorems.
AB  - For a continuous self mapping f of a locally convex topological vector space
      which is locally compact (i.e., f maps a neighborhood of each point into a
      relatively compact set), it is shown that a sufficient condition for the
      existence of a fixed point is the existence of a compact attractor K(0) such that
      each orbit under f has a point of K(0) in its closure. The proof is based upon
      the circle of ideas of the Lefschetz fixed point theorem.

PMID- 16592170
TI  - Dissipative structures, catastrophes, and pattern formation: a bifurcation
      analysis.
AB  - A model chemical network involving reactions and diffusion is studied. Spatially
      and temporally ordered solutions of the equations are found by bifurcation
      theory. These solutions are calculated analytically and their stability is
      studied. Properties of these dissipative structures are discussed, and a
      comparison with Thom's theories of morphogenesis is outlined.

PMID- 16592171
TI  - Nonasymptotic species richness models and the insects of british trees.
AB  - Nonasymptotic models of species diversity are those that do not consider negative
      feedback between number of species in a biota and the net rate of species
      addition. These models propose species richness differences to be primarily the
      product of geologic age differences among biotas. Nonasymptotic explanations are
      traditional for various diversity difference spectra, including latitudinal
      diversity gradients and the greater species richness of ancient compared to young
      lakes. I review new evidence that renders these nonasymptotic explanations
      doubtful.The only uncontested evidence in favor of nonasymptotic species
      accumulation is Southwood's correlation between the number of insect species
      associated with British tree taxa and the number of Quaternary fossil records of
      these taxa. I show that nonasymptotic explanations of species richness variation
      are unacceptable for this system also. The variation in insect species richness
      among these taxa is well accounted for by a species-area relationship. The
      species richness asymptote is attained within a few hundred years, and the
      influence of cumulative host taxon abundance (number of fossil records) upon
      insect species richness is insignificant after the statistical influence of
      present-day host plant range is removed. I conclude Southwood's correlation to
      lack causality; it probably derives from a correlation between the number of
      fossil records of the host taxa and their present range.

PMID- 16592172
TI  - The pairwise correlated generalized valence bond model of electronic structure I;
      the estimation of pair energies from orbital overlaps.
AB  - A new method for the accurate a priori calculation of atomic and molecular
      energies is proposed. The new method agrees with experiment to within less than 1
      kcal/mole in all cases examined thus far, and is applicable to excited states and
      to transition states for chemical reactions. Since the new method corrects the
      results of generalized valence bond calculations for the effects of electron pair
      correlations, we call the new method the pairwise correlated generalized valence
      bond method.

PMID- 16592173
TI  - Resonance between a Prolate and a Superprolate Structure of the Er Nucleus.
AB  - Observed energy levels of (162)Er from the normal state J = 0 to the excited
      rotational state J = 18 correspond to values of the moment of inertia and
      rotational frequency that indicate that a pronounced change in structure occurs
      at about J = 14. It is shown that the observed values agree well with the values
      calculated on the assumption that there is resonance between a more stable
      prolate structure with a core of two spherons and a less stable superprolate
      structure with a core of three spherons in line.

PMID- 16592174
TI  - Subellipticity on pseudo-convex domains with isolated degeneracies.
AB  - Previous work has lead the author to conjecture necessary and sufficient
      conditions for the subellipticity of the [unk]-Neumann problem on pseudoconvex
      domains. Here we outline a general method which reduces the problem of
      subellipticity to inequalities between germs of C(infinity) functions. We then
      describe how this method can be applied to prove the sufficiency of the
      conditions on domains whose boundaries have an isolated set of points on which
      the Levi form degenerates and such that in a neighborhood of these points the
      boundary is real analytic.

PMID- 16592175
TI  - Diffusivity of gases in liquids.
AB  - Diffusion coefficients of H(2), Ne, N(2), Ar, CH(4), Cl(2), CF(4), C(2)H(6),
      SF(6), I(2), and isotopic CCl(4), all in CCl(4), determined at atmospheric
      pressure, are linear functions of temperature, converging to zero at the
      temperature where CCl(4) ceases to be fluid. The slopes of these lines increase
      with decreasing molecular cross-section of the diffusants, and with increasing
      entropy of expansion of the diffusants in CCl(4). Diffusivities in
      (C(4)F(9))(2)N, whose molecules are very large and three-armed, do not converge
      as temperature is decreased. Molecules of H(2), Ne, and, to a lesser extent, Ar,
      are able to diffuse in (C(4)F(9))(2)N even at temperatures where fluidity is low.

PMID- 16592176
TI  - Study of vibronic and born-oppenheimer couplings.
AB  - The purpose of this paper has been to develop a systematic approach for
      classifying and distinguishing the relative orders of approximation of various
      types of couplings like the vibronic (Herzberg-Teller) couplings and Born
      Oppenheimer couplings, and for studying the importance of the anharmonicity in
      the quantitative calculation of the spectral intensity and electronic relaxation.
      It will be shown that the perturbation parameter introduced by Born and
      Oppenheimer in separating the electronic and nuclear motion involved in the
      molecular Schrodinger equation, lambda = (m/M)(1/4), can be used for this purpose
      by expanding wavefunctions and energies in power series of lambda.

PMID- 16592177
TI  - Multivariate approximation by locally blended univariate interpolants.
AB  - A method is given for constructing simple new "finite elements" that seem well
      suited to approximating smooth functions in rectangular polygons decomposed into
      rectangular cells. Some of the key properties of the elements are derived, and
      analogous three-dimensional "bricks" are constructed.

PMID- 16592178
TI  - Electron transfer between biological molecules by thermally activated tunneling.
AB  - A theory of electron transfer between two fixed sites by tunneling is developed.
      Vibronic coupling in the individual molecules produces an activation energy to
      transfer at high temperatures, and temperature-independent tunneling (when
      energetically allowed) at low temperature. The model is compared with known
      results on electron transfer in Chromatium and in Rhodopseudomonas spheroides. It
      quantitatively interprets these results, with parameters whose scale is verified
      by comparison with optical absorption spectra. According to this description, the
      separation between linking sites for electron transfer is 8-10 A in Chromatium,
      far smaller than earlier estimates.

PMID- 16592179
TI  - Molecular basis for the photosynthetic primary process.
AB  - In this paper, the molecular details for the primary reaction in photosynthesis
      are deduced from several recent critical experimental observations. A symmetrical
      structure is proposed for the basic unit of the reaction center in plant
      photosynthesis. A mathematical consequence of the symmetrical arrangement is the
      creation of an anomalously long-lived trap state, which makes possible the
      summation of a reaction-center triplet excitation and an antenna chlorophyll
      singlet excitation to bring the photoactive chlorophylls to a charge-transfer
      state prior to entering into a primary photochemical reaction.

PMID- 16592180
TI  - Refinement of the X-ray Structure of Rubredoxin by Conformational Energy
      Calculations.
AB  - The x-ray structure of rubredoxin has been refined by energy minimization. The
      computed structure is constrained to have standard bond lengths, bond angles, and
      planar trans peptide groups. Also, since most of the steric overlaps have been
      relieved, it has a very low energy. As judged by the root mean square (RMS)
      deviation of the computed coordinates from those of the x-ray structure, the two
      are very similar. The reliability index R for the computed structure (determined
      from the structure factors for the calculated conformation) is 0.37, which is
      comparable to that for other proteins.

PMID- 16592181
TI  - Critical length of the transport-dominated region for oscillating non-linear
      reactive processes.
AB  - Beyond an instability, non-linear processes can give rise to reactive modes
      exhibiting sustained oscillations in particle numbers. The coupling of such an
      oscillatory mode to diffusional transport in a system can cause coherent spatio
      temporal structures to arise and persist indefinitely, far from thermal
      equilibrium, provided the system is above some critical size and is maintained
      open to mass and energy transfer.In the case of one spatial dimension, the
      critical size of the system, following Goldbeter [Proc. Nat. Acad. Sci. USA 70,
      3255-3259 (1973)], can be defined as that size up to which there exists exactly
      one unique time-independent solution (which is completely transport dominated) to
      the macroscopic equation that characterizes the coupling of the reactive mode to
      diffusional transport and which is subject to inhomogeneous boundary conditions.
      A theoretical estimate of the critical size is derived (valid for arbitrary
      systems involving multicomponent non-linear reactive processes possessing an
      oscillatory mode) by making use only of the parameter-dependent period of the
      oscillatory mode and of the elements of the diffusion tensor. This estimate
      specifically takes cross-diffusion into account. In the special case of simple
      diagonal diffusion, an illustrative comparison is made with the prediction of a
      more model-specific estimate of Goldbeter that involves a model for glycolytic
      oscillations.

PMID- 16592182
TI  - Diffusivity of Methane in a Mixture of CCl(4) and c-C(6)F(11)C(2)F(5) of the
      Critical Composition in the Region above the Temperature of Separation.
AB  - The diffusivity of CH(4) in a mixture of CCl(4) and c-C(6)F(11)C(2)F(5) of the
      critical composition in the region of temperature close to that of unmixing,
      decreases as in a homogeneous liquid from 36 degrees to about 32 degrees . It
      then passes through a minimum of 10(5)D approximately 4.15 cm(2)/sec at about
      27.5 degrees , then rises to 10(5)D = 4.61 at 25.00 degrees , then steeply to
      6.36 cm(2)/sec in the further drop of only 0.3 degrees to 24.71 degrees .

PMID- 16592183
TI  - Study of the franck-condon and herzberg-teller approximations.
AB  - Using the Born-Oppenheimer parameter lambda = (m/M)(1/4) as a perturbation
      parameter, we find that for allowed transitions, the zeroth order approximation
      of the spectral intensity gives rise to the Condon approximation, the first order
      vibronic coupling and anharmonic effect appear in the first order approximation
      of the spectral intensity, which gives us the non-Condon scheme, and only the
      intensity of the transitions of totally-symmetric modes with nonvanishing normal
      coordinate displacements is affected by the inclusion of the first order vibronic
      coupling and anharmonic effect. For symmetry-forbidden but vibronic-allowed
      transitions, the first nonvanishing term of the spectral intensity is second
      order with respect to lambda and the B-O couplings do not appear in the
      calculation of the spectral intensity until the fourth order approximation with
      respect to lambda; in this case, other high order vibronic couplings and
      anharmonic effect are competing with the B-O couplings.

PMID- 16592184
TI  - L-multipliers for Noncompact Symmetric Spaces.
AB  - Let G be a real noncompact semi-simple Lie group with finite center and K a
      maximal compact sub-group. The symmetric space M = G/K carries a measure
      invariant under the action of G. The operators which map L(p)(M) continuously
      into itself and commute with the action of G, can be easily characterized when p
      = 2 or p = 1. This note gives some results on "singular integrals" which map L(p)
      into itself (1 < p < + infinity).

PMID- 16592185
TI  - Geographical coincidence of high heat flow, high seismicity, and upwelling, with
      hydrocarbon deposits, phosphorites, evaporites, and uranium ores.
AB  - Oil deposits occur in deep sediments, and appear to be organic matter that has
      been transformed through the action of geothermal heat and pressure. Deep
      sediments, rich in biological remains, are created by ocean upwelling, caused in
      part by high geothermal heat flow through the sea bottom. Such regions correlate
      with enhanced seismic activity. We look for correlations of seismicity, high heat
      flux, petroleum, uranium, phosphates, and salts, deposited from abundant plant
      life. These may be useful in discovering more petroleum and coal. We estimate
      that the known world reserves of petroleum and coal are about 10(-4) of the total
      of buried biogenic carbon.

PMID- 16592186
TI  - Generalization of Recent Method Giving Lower Bound for N(o)(T) of Riemann's Zeta
      Function.
AB  - Let h(s) = pi(-s/2)tau(s/2). Then, h(s)zeta(s) approximately h(s)H(s) + h(1 -
      s)H(1 - s) where H(s) = Sigma(1 - (log n)/log t/2pi)n(-s), n </= t/2pi, led to
      N(o)(T) >/= N(T)/3. Here the extension to H(s) approximately Sigma P (1 - (log
      n)/log t/2pi) n(-s) is made where P(x) is a polynomial such that P(0) = 0 and
      P(x) + P(1 - x) = 1. The earlier case is P(x) = x. The relevant formulas in the
      general case can be obtained explicitly by the earlier method used for P(x) = x,
      and, indeed, in some respects there is greater simplicity for the general case.

PMID- 16592187
TI  - An analytic generalization of the rogers-ramanujan identities for odd moduli.
AB  - A (k - 1)-fold Eulerian series expansion is given for II(1 - q(n))(-1), where the
      product runs over all positive integers n that are not congruent to 0,i or - i
      modulo 2k + 1. The Rogers-Ramanujan identities are the cases k = i = 2 and k = i
      + 1 = 2.

PMID- 16592188
TI  - Giemsa C-banding and the evolution of wheat.
AB  - The somatic chromosomes of common wheat, Triticum aestivum L. (2n = 6x = 42), and
      those of two of its diploid progenitors and T. speltoides, have been individually
      identified by a Giemsa staining technique. In wheat, telocentric chromosomes were
      used to aid the recognition of individual chromosomes, and an ideogram has been
      constructed depicting the C-band positions. There is no similarity in the C
      banding of chromosomes within a homoeologous group, with the possible exception
      of group 5. Comparisons of the C-banding of the diploid species T. monococcum, T.
      speltoides, and T. tauschii with that of the A, B, and D genomes, respectively,
      in hexaploid wheat corroborate that T. speltoides could not be the donor of the B
      genome to wheat and that T. monococcum and T. tauschii are the probable donors of
      the A and D genomes, respectively.

PMID- 16592189
TI  - Characterization of fourier transforms of hardy spaces.
AB  - Characterizations of Fourier transforms of boundary distributions of functions in
      H(p)(R) or H(p)(T), 0 < p </= 1, are given. These results are applied to obtain
      Fourier multiplier theorems on H(p).

PMID- 16592190
TI  - The compression hypothesis and temporal resource partitioning.
AB  - Contingency models of feeding compare the energy per unit time gained from
      utilizing a resource unit of a particular kind (food types, habitat patches, time
      periods) against that energy/time expected if the unit is skipped. Optimally, an
      animal should reject the particular unit if and only if the former energy/time is
      less than the latter. Consequently, food or habitat types should be excluded if
      the prospect of finding and consuming better types is sufficiently high. In
      contrast, feeding periods should be skipped only if it is less costly to wait
      than to feed.In situations of high food abundance, contingency models imply that
      animals should be maximally specialized with respect to food or habitat type, but
      maximally generalized with respect to time period. As food decreases in
      abundance, food and habitat types should be added to the diet or itinerary, but
      time periods should be omitted from feeding activity. In contrast, animals with
      fixed caloric intake should broaden diet, habitat, and feeding times as abundance
      decreases.According to contingency models, competitors cannot cause item kinds to
      be dropped from the diet, but because they can affect the values of patches once
      found, can cause habitat kinds to be dropped from the itinerary. Competitors also
      reduct the value of feeding during particular time periods, but ordinarily fairly
      severe depletion must occur before it is optimal to feed no longer in a period
      frequented by competitors.These arguments imply that temporal resource
      partitioning on a diel basis should be relatively rare. In fact, specialization
      according to feeding period should differentially occur in animals of limited
      abilities to use or process available food, whereas that need not be the case for
      food-type or habitat specialization. It should also occur in animals sensitive to
      and found in variable climates.

PMID- 16592191
TI  - The toxin-binding protein of sugarcane, its role in the plant and in disease
      development.
AB  - The toxin-binding protein of sugarcane susceptible to eyespot disease also
      possesses raffinose-binding activity. The K(m)'s for binding are:
      helminthosporoside (toxin) 6.8 x 10(-5) M, raffinose 2.5 x 10(-5) M, and
      melibiose 2.6 x 10(-5) M. Evidence obtained by administering [(14)C]raffinose to
      sugarcane protoplasts suggests that this protein participates in alpha
      galactoside transport. Cells from a resistant clone of sugarcane do not possess
      an active-binding protein, and likewise, do not actively take up raffinose.
      Interestingly, the K(+), Mg(++) ATPase (ATP phosphohydrolase, EC 3.6.1.3.) on the
      plasma membrane of the susceptible sugarcane is 30% activated by the toxin at 3
      mM. In addition, toxin-treated tissue slices show a rapid uptake of (86)Rb(+)
      K(+) which is in agreement with the toxin activation of the membrane K(+), Mg(++)
      ATPase. Since the ATPase does not directly interact with the toxin, the
      activation effect occurs by means of the toxin-binding protein. Membrane proteins
      may be influenced by the toxin-binding protein acting by one of several different
      mechanisms.

PMID- 16592192
TI  - Applications of the survival theory to ecology.
AB  - The Eyring-Stover theory of survival developed in earlier papers can be readily
      applied to a wide diversity of ecological phenomena, with implications for
      identifying basic responses of organisms to their environment. We report several
      examples to demonstrate the generality of the theory.

PMID- 16592193
TI  - Serendibite, a complicated, new, inorganic crystal structure.
AB  - Serendibite with very similar analyses is known from Ceylon and New York. The
      triclinic cell of symmetry P[unk] and volume 670.9 A(3) contains
      2Ca(1.64)Mg(2.64)Fe(0.27) (II)Al(4.64)B(1.66)Si(3)O(20), with 14 metal atoms and
      20 oxygen atoms in the asymmetric unit. It was solved by the "direct" method of
      transforming the ordinary three-dimensional Patterson function into an
      approximation of the electron density by using conjugate peaks and minimum
      functions, followed by successive Fourier syntheses and least-squares refinement
      to R = 7.1%. This new structure is composed of interrupted brucite-type layers
      which form an octahedral framework, and winged single chains of tetrahedra. The
      structure has units of similar, but not identical, geometry to those of the
      minerals sapphirine and aenigmatite, and these similar units are assembled in a
      different way.

PMID- 16592194
TI  - Alignment of the Earth's Magnetic Field with the Axis of Rotation and Reversals
      of Polarity: Laboratory Experiments on a Mechanism.
AB  - A mechanism that can cause the earth's external magnetic field to be aligned with
      the axis of rotation and to reverse at random times is described. It depends upon
      two arbitrary assumptions: (a) A dipole magnetic source, of unspecified nature,
      deep within the core, wanders randomly in direction. (b) The conducting fluid at
      the outer boundary of the core circulates in a pattern that is symmetrical with
      respect to the earth's axis of rotation. It is shown that such a circulating
      layer will act as an anisotropic screen, which will suppress the field of the
      transverse component of the source dipole. The field observed outside the core
      will be mainly that of the axial component of the source, and it will reverse
      abruptly whenever the direction of the source crosses the equatorial plane.
      Quantitative experimental studies, made on small-scale models, of the effects and
      their properties are described. The only datum that even suggests a value that
      may be used for the angular velocity of the circulating outer layer with respect
      to the source is the angular velocity of the westward drift of the earth's
      nondipolar field. If that value is used, the anisotropic screening effect comes
      out to be strong enough to give alignment and reversal characteristics that are
      similar to those found from paleomagnetic studies.

PMID- 16592195
TI  - Closed leaves in foliated 3-manifolds.
AB  - The purpose of this note is to sketch some results on the existence and
      properties of multi-holed toral leaves in foliations of closed, orientable 3
      manifolds. The complete proofs of these results will appear elsewhere.

PMID- 16592196
TI  - A sequential test for two binomial populations.
AB  - A sequential procedure is proposed for deciding which of two sequences of
      Bernoulli trials has the greater success probability. The procedure covers cases
      in which the two sequences are being observed at different rates, whether by
      design or otherwise, as well as the case of pairwise observation. The error
      probability of the procedure depends approximately only on the odds ratio of the
      two probabilities, a desirable property in deciding which of two medical
      treatments has the greater probability of success.

PMID- 16592197
TI  - On the mechanism of oscillations in the "beating mercury heart".
AB  - The discovery of a class of electrochemical-mechanical oscillators-similar to the
      beating mercury heart -are reported and characterized. Chemical and physical
      effects on the voltage-time oscillations in these systems have been measured and
      a mechanism consistent with these effects is given. Interesting cross-catalytic
      effects involving the electrocapillarity of mercury are proposed to be the origin
      of the oscillations in these systems.

PMID- 16592198
TI  - Parametric analysis of conductance data.
AB  - It is shown that three and only three parameters are sufficient to generate a
      function Lambda (c; Lambda(0), K(A), R) which reproduces observed equivalent
      conductance Lambda as a function of concentration c within experimental error up
      to concentrations of about 2 x 10(-7)D(3) eq/liter (D = dielectric constant). The
      three parameters are: Lambda(0), the limit of Lambda(c) at zero concentration;
      K(A), the association constant; and R, a distance. Realization that conductance
      data can provide only one distance parameter suggests a model for electrolytic
      solutions in which R is defined as the radius of the sphere inside of which a
      unique partner can be found for a paired ion, and outside of which continuum
      theory may be applied. All system-specific effects (ion-ion and ion-solvent
      interactions, and the inherent spatial discontinuity of real solutions) appear
      within the spheres of radius R centered at the cations of the ion pairs. The
      association constant therefore depends not only on electrostatic attraction but
      also on the multiplicity of molecular parameters that are needed to describe
      short range interactions.

PMID- 16592199
TI  - Chemical composition of nebulosities in the magellanic clouds.
AB  - From photoelectric spectrophotometric data secured at Cerro Tololo Interamerican
      Observatory we have attempted to derive electron densities and temperatures,
      ionic concentrations, and chemical abundances of He, C, N, O, Ne, S, and Ar in
      nebulosities in the Magellanic Clouds. Although 10 distinct nebulosities were
      observed in the Small Cloud and 20 such objects in the Large Cloud, the most
      detailed observations were secured only for the brighter objects. Results for 30
      Doradus are in harmony with those published previously and recent work by
      Peimbert and Torres-Peimbert. Nitrogen and heavier elements appear to be less
      abundant in the Small Cloud than in the Large Cloud, in accordance with the
      conclusions of Dufour. A comparison with the Orion nebula suggests He, N, Ne, O,
      and S may all be less abundant in the Megellanic Clouds, although adequate
      evaluations will require construction of detailed models. For example, if we
      postulate that the [NII], [OII], and [SII] radiations originate primarily in
      regions with electron temperatures near 8000 degrees K, while the [OIII],
      [NeIII], [ArIII], and H radiations are produced primarily in regions with
      T(epsilon) = 10,000 degrees K, the derived chemical abundances in the clouds are
      enhanced.

PMID- 16592200
TI  - A new method for congressional apportionment.
AB  - The problem of Congressional apportionment is explained together with a brief
      history of the methods used or considered for its solution. Reasons are given for
      rejecting the presently used method of equal proportions and for accepting a new
      method, the quota method, which is the unique method satisfying three essential
      axioms.

PMID- 16592201
TI  - Singular Integrals and the Principal Series, III.
AB  - The intertwining operators for nonunitary principal series representations of a
      real semisimple Lie group are used to construct intertwining operators for all
      the series of unitary representations appearing in the Plancherel formula. The
      resulting machinery reduces computations with Harish-Chandra's c-functions and
      the Plancherel measure to computations with those c-functions and measures
      obtained from a minimal parabolic subgroup.

PMID- 16592202
TI  - A statistical study of optical rotation for synthetic d,l-copolypeptide
      solutions.
AB  - The right-handed helical fraction H(L) in a D,L-copolypeptide chain is evaluated
      by a simple probability theory for each L-fraction, p. The curves of optical
      rotation at a single wavelength against p for poly(gamma-benzyl-D,L-glutamate)
      and D,L-copolyleucine of a series of different D:L ratios in several positive
      helix-solvents are calculated with a modified semi-empirical Moffitt equation.
      From the comparison between the rotations calculated by us and observed by Downie
      et al., it is shown that to reproduce the observed rotations, the minimum number
      of right-handed helical nuclei or sequences of L-residues appropriate to the
      Moffitt equation are eight and four for degrees of polymerization 320 and 1860,
      respectively.

PMID- 16592203
TI  - The effect of bicarbonate on photosynthetic oxygen evolution in flashing light in
      chloroplast fragments.
AB  - The ability of bicarbonate ion (HCO(3) (-)) to stimulate photosynthetic oxygen
      evolution in maize chloroplast fragments exposed to continuous light depends on
      light intensity. Stimulation by HCO(3) (-) is less at low intensities. In HCO(3)
      (-)-depleted chloroplasts exposed to brief saturating light flashes, period 4
      oscillations (in O(2) yield per flash) are damped within three cycles. Readdition
      of HCO(3) (-) to these preparations restores the oscillatory pattern to higher
      flash numbers, indicating that HCO(3) (-) reduces the probability of "misses" in
      the photosystem II reaction center. The rate of the dark relaxation reaction S(n)
      (') --> S(n+1) (where S refers to the oxidation state of the oxygen-evolving
      mechanism and n = 0, 1, or 2), after a photoact in the photosystem II reaction
      center, is retarded in HCO(3) (-)-depleted chloroplasts compared to the rate for
      this reaction in depleted chloroplasts to which HCO(3) (-) has been resupplied.
      However, the final oxygen-evolving reaction after the accumulation of four
      positive charges appears to be independent of HCO(3) (-). Bicarbonate has no
      effect on the dark deactivation of the higher oxidation states (S(2) and S(3)) of
      the positive charge-accumulating system. We propose two alternate ways in which
      the kinetic model of oxygen evolution developed by Kok et al. [(1970) Photochem.
      Photobiol. 11, 457-475] can be extended to include the action of HCO(3) (-).

PMID- 16592204
TI  - High pressure studies of solvent effects on anthracene spectra.
AB  - Measurements have been made of the effect of pressure on the peak location and
      peak shape for anthracene in a variety of liquid and plastic environments; both
      absorption and fluorescence studies were made. The results are discussed from two
      standpoints: in terms of the dielectric model and of a configuration coordinate
      model. For the latter model, the change of configuration coordinate (volume
      decrease of the system upon electronic excitation) is shown to correlate well
      with the product of the compressibility and polarizability of the solvent. For
      the dielectric model, it is found that the change of cavity volume with density
      is complex. However, the relative cavity volume obtained from emission
      measurements was consistently 10-15% smaller than that obtained from absorption.
      The cavity volume decreased with increasing polarizability of the solvent, and
      results obtained from absorption and emission were quite consistent in this
      regard.

PMID- 16592205
TI  - The stars of low luminosity.
AB  - A search has been made among the faint stars with large proper motion found on
      the Palomar Survey plates for objects that, statistically-judging from their
      magnitude, color, and proper motion-would appear to be fainter than one ten
      thousandth of the sun's luminosity. A total of 122 such objects have been found,
      and an analysis made for solar motion among them does, indeed, indicate that they
      must be of exceedingly low luminosity.

PMID- 16592206
TI  - An electron-nuclear double resonance (ENDOR) study of the special pair model for
      photo-reactive chlorophyll in photosynthesis.
AB  - A comparison of hyperfine coupling constants obtained by electron-nuclear double
      resonance spectroscopy of in vitro monomer chlorophyll and bacteriochlorophyll
      free radicals with those of the photoesr (electron spin resonance) signal
      associated with light conversion in photosynthesis provides convincing support
      for the special pair model for the in vivo photo-reaction center.

PMID- 16592207
TI  - Photon propagation function: a comparison of asymptotic functions.
AB  - An earlier paper asserts the logarithmic asymptotic identity of various
      asymptotic functions associated with the photon propagation function, including
      the spectral weight function and the Gell-Mann-Low function. This note exhibits
      explicit expressions for the deviations between pairs of functions. It is
      emphasized that the differences are quantitatively small, and that the various
      functions have common qualitative characteristics. The discussion refers to a
      particular method for comparing the functions, which has no special physical
      status. When that restriction is removed, it becomes possible to prove the
      general existence of a transformation of variable that will produce the Gell-Mann
      Low function from the spectral weight function. This supplies a physical
      interpretation that has otherwise been missing in the Gell-Mann-Low approach.

PMID- 16592208
TI  - Source theory viewpoints in deep inelastic scattering.
AB  - The phenomena of deep inelastic electron scattering on single nucleons, viewed as
      virtual photon absorption, are reexamined with the nonspeculative,
      phenomenological attitude of source theory. The use of a double spectral
      representation for forward scattering, and of experimental inputs from the low
      energy resonance region and the high energy real photon diffraction region, lead
      naturally to the general observed characteristics of deep inelastic scattering. A
      reasonably successful description of deviations from simple scaling behavior is
      also presented.

PMID- 16592209
TI  - Kinetics of the decomposition of hydrogen peroxide catalyzed by ferric
      ethylenediaminetetraacetate complex.
AB  - Added substrates, acetone and t-butyl alcohol, strongly retard the decomposition
      of H(2)O(2) brought about by ferric ethylenediaminetetraacetate (EDTA) at pH 8
      9.5. Their relative effectiveness and the kinetic form of the retardation are
      consistent with their interruption of a hydroxyl radical chain that is propagated
      by HO. attack both upon H(2)O(2) and on complexed and uncomplexed EDTA. Similar
      retardation is observed with decompositions catalyzed by ferric nitrilotriacetate
      and hemin, and it is proposed that such redox chains may be quite a general path
      for transition metal ion catalysis of H(2)O(2) decomposition.

PMID- 16592210
TI  - Sequential Estimation of p with Squared Relative Error Loss.
AB  - We consider the sequential estimation of p, the probability of success in an
      infinite sequence of Bernoulli trials, when the loss incurred in stopping after n
      trials and estimating p by some function delta(n) of the first n outcomes is
      taken to be [Formula: see text] The loss due to error of estimation is thus the
      symmetrized relative squared error, which is appropriate in applications when p
      may be near 0 or 1.We begin by finding a heuristic procedure for sequentially
      determining the sample size n which, with the usual terminal estimator of p,
      performs well for any fixed 0 < p < 1 as the cost per observation c --> 0. For
      any fixed c > 0, however, this procedure is poor as p --> 0 or 1. To remedy this
      defect, the uniform prior on p is introduced. The corresponding Bayes procedure
      is found and is shown to have a Bayes risk approximately 2pi radicalc as c --> 0.

PMID- 16592211
TI  - The Acid-Base Properties, Hydrolytic Mechanism, and Susceptibility to O(2)
      Oxidation of Fe(4)S(4)(SR)(4) Clusters.
AB  - The iron-sulfur cluster compounds Fe(4)S(4)(SR)(4) (-2) [where -SR = -SCH(3), -S
      C(CH(3))(3), and -S- CH(2)-CH(CH(3))(2)] have been found to represent the base
      species of weak acids of pK(a) comparable to that of carboxylic acids. The acid
      species Fe(4)S(4)(SR)(4)H(-) is most subject to reaction with O(2) and to acid
      catalyzed solvolysis, while the base species Fe(4)S(4)(SR)(4) (-2) most readily
      undergoes ligand exchange. The kinetics for hydrolysis of the isobutyl mercaptide
      cluster salt has been investigated in detail and a mechanism involving the
      stepwise process [Formula: see text] has been proposed. The importance of the
      acid-base equilibria in determining the reactivity of the iron-sulfur clusters
      and its possible importance as a factor in the determination of the potentials of
      ferredoxins and high potential iron protein are discussed.

PMID- 16592212
TI  - The Alkali Ion-DNA Interaction as Reflected in the Nuclear Relaxation Rates of Na
      and Rb.
AB  - Longitudinal relaxation rates of (23)Na and (87)Rb in aqueous solutions of DNA
      were measured and interpreted in terms of contributions of "bound" and free
      species. The frequency dependence of the (23)Na relaxation rate sets an upper
      limit of 5.5 nsec for the correlation time characteristic of the alkali ion-DNA
      interaction. The plausible description of the alkali ion-DNA interaction emerging
      from the results is one in which the "bound" ions comprise a highly mobile ionic
      cloud around the lattice of phosphate groups with a population characterized by
      an apparent dissociation constant of 10.9 mM. Any specific binding to phosphate
      groups involving severe restrictions of motional freedom must be much (at least
      two orders of magnitude) weaker and of a very short duration (<5.5 nsec).

PMID- 16592213
TI  - Condensation time of the solar nebula from extinct I in primitive meteorites.
AB  - Mineral separates from five carbonaceous chondrites were dated by extinct 16
      million year (129)I, in an attempt to establish the condensation time of the
      solar nebula. Two Fe(3)O(4) or Fe(3)O(4)-FeS samples from the Murchison and
      Orgueil meteorites are older than any other material dated thus far, and
      apparently formed within 2 x 10(5) years of each other. The great age, close
      isochronism, and primitive nature of the samples suggest that the event recorded
      was the condensation stage of the solar nebula. It provides a suitable zero point
      for the chronology of the early solar system. The (129)I/(127)I ratio during
      condensation of the nebula was (1.46 +/- 0.04) x 10(-4). The recrystallized C4
      chondrite Karoonda began to retain (129)Xe 1.8 +/- 0.5 million years after the
      above event. This short cooling time implies rapid aceretion (</=1 million years)
      and a shallow origin (</=10 km) below the surface of its parent body.

PMID- 16592214
TI  - Deduction of Semi-Optimal Mollifier for Obtaining Lower Bound for N(0)(T) for
      Riemann's Zeta-Function.
AB  - A mollifier played a key role in showing N(0)(T) > 1/3N(T) for large T in ref. 1
      [Levinson, N. (1974) Advan. Math. 13, 383-436]. A basic problem in ref. 1 was
      that of obtaining an upper bound for a sum of two terms, one larger than the
      other. Here a deductive procedure is given for finding a mollifier that actually
      minimizes the larger term. An Euler-Lagrange equation is obtained. (Optimization
      of the sum of both the major and minor terms appears to be formidable.) The
      actual improvement effected by the optimized mollifier over the ad hoc mollifier
      of ref. 1 is unfortunately only 1.4%. To obtain a usable mollifier it is
      necessary to blur the optimization procedure by smoothing at several stages of
      the deduction. The procedure is of more interest than the particular application
      because of the small improvement in this case.

PMID- 16592215
TI  - Neutron diffraction studies on the location of water in lecithin bilayer model
      membranes.
AB  - Lamellar neutron diffraction from oriented multilayers of hydrated dipalmitoyl
      lecithin was phased by isomorphous H(2)O-D(2)O exchange and swelling techniques.
      Bound water sites were located in the polar head group region of the bilayer
      profile. A 6-A resolution structure based on the neutron scattering density
      profile is proposed for the bilayer. It is consistent with the electron density
      profile from x-ray diffraction.

PMID- 16592216
TI  - Crystallization and crystal data of monellin.
AB  - Crystals of monellin, a sweet protein from Dioscoreophyllum cumminsii, were grown
      by vapor diffusion of 20% ethanol into buffered protein solution. The crystals
      are orthorhombic, belonging to space group P2(1)2(1)2, with a = 54.4 A, b = 113.0
      A, c = 40.8 A, and V = 250,300 A(3). The asymmetric unit contains two complete
      molecules of monellin. The diffraction pattern of this crystal form extends to at
      least 2.5 A, indicating that x-ray structural analysis is possible to near-atomic
      resolution.

PMID- 16592217
TI  - The significant structure theory applied to a mesophase system.
AB  - The significant structure theory of liquids is extended to the mesophase system
      with p-azoxyanisole as an example. This compound has two different structures, a
      nematic phase and an isotropic phase, in its liquid state. In this study the
      nematic phase is treated as subject to a second volume and temperature-dependent
      degeneracy formally like that due to melting. The isotropic phase is treated as a
      normal liquid. The specific heat, thermal expansion coefficient, compressibility,
      volume, entropy of transitions, and heat of transitions are calculated and
      compared to the observed values. This analysis differs from previous ones in
      including the volume dependence as well as the temperature dependence in one
      explicit expression for the Helmholtz free energy.

PMID- 16592218
TI  - Magnetic Circular Dichroism of Molecules in Dense Media: Relation Between
      Magnetic Circular Dichroism and Hammett's Constants.
AB  - The linear relation between the magnetic circular dichroism (benzene (1)A(1g) -->
      (1)B(2u) transition) of monosubstituted and 1,4-disubstituted benzenes and the
      substituent constants sigma and sigma(R) are compared. In all cases, better
      linear correlations were found between the magnetic circular dichroism and
      sigma(R). Three series of 1,4-disubstituted benzenes, XC(6)H(4)I, XC(6)H(4)NO(2),
      and XC(6)H(4)CO(2)H, have been chosen for the magnetic circular dichroism
      measurements.

PMID- 16592219
TI  - Insertion Compounds of 2H-TaS(2).NH(3).
AB  - A new method of intercalating metals into layer compounds has been developed
      using electrolytic generation from the salt solution in ammonia. The results
      suggest that metals that are soluble in ammonia will form a homogeneous metal
      ammonia intercalate layer, NH(3).M(x), when x is less than the limiting
      solubility of M in NH(3). The superconducting transition temperature (T(c)) was
      found to increase as the c-axis expansion [2delta = c(TaS(2).NH(3).M(x)) - c(2H
      TaS(2))] decreased when M = lithium, sodium, and potassium. Of all the alkali
      metals, potassium gave the most stable compounds and the highest T(c), 4.7
      degrees K.

PMID- 16592220
TI  - Motion of a slightly compressible fluid.
AB  - We show that the motion of a slightly compressible fluid is near that of an
      incompressible fluid. That is, for a given initial velocity field, the motion of
      a compressible fluid with large sound speed is near to that of an idealized
      incompressible fluid. We consider the compressible fluid motion in Lagrangian
      coordinates and show that it can be defined by two functions giving the kinetic
      and potential energies. The minimal set for the potential energy is the
      configuration space of incompressible fluid motion. If the equation of state of
      the compressible fluid is changed so that the sound speed increases, the minimum
      of the potential energy function becomes sharper. The compressible fluid motion
      approaches a curve in the minimal set and this curve defines an incompressible
      fluid motion.

PMID- 16592221
TI  - A new approach to empirical intermolecular and conformational potential energy
      functions. I. Description of model and derivation of parameters.
AB  - An empirical potential energy function based on the interactions of the electrons
      and nuclei in molecules has been developed and tested. The potential energy of
      interaction is approximated by the sum of the coulombic interactions between all
      point charge centers (electrons and nuclei), an exponential repulsion to
      represent electron-electron overlap repulsion, and an R(-6) (R = distance)
      attraction to simulate dispersion and other attractive energies between the heavy
      atom fragments of the molecules. The parameters of the potential energy function
      have been determined from experimental gas-phase and crystal data.The results
      indicate that both intramolecular and intermolecular interaction energies can be
      treated with the same set of parameters. In comparison to other empirical
      interaction potentials now in use, there are fewer independent parameters, there
      is no need for intrinsic torsional potentials to obtain the correct rotational
      barriers, and there is no need for special hydrogen bonding functions to account
      for the directionality and energetics of hydrogen bonding.

PMID- 16592222
TI  - The power of the optimal asymptotic tests of composite statistical hypotheses.
AB  - The easily computable asymptotic power of the locally asymptotically optimal test
      of a composite hypothesis, known as the optimal C(alpha) test, is obtained
      through a "double" passage to the limit: the number n of observations is
      indefinitely increased while the conventional measure xi of the error in the
      hypothesis tested tends to zero so that xi(n)n((1/2)) --> tau not equal 0.
      Contrary to this, practical problems require information on power, say
      beta(xi,n), for a fixed xi and for a fixed n. The present paper gives the upper
      and the lower bounds for beta(xi,n). These bounds can be used to estimate the
      rate of convergence of beta(xi,n) to unity as n --> infinity. The results
      obtained can be extended to test criteria other than those labeled C(alpha). The
      study revealed a difference between situations in which the C(alpha) test
      criterion is used to test a simple or a composite hypothesis. This difference
      affects the rate of convergence of the actual probability of type I error to the
      preassigned level alpha. In the case of a simple hypothesis, the rate is of the
      order of n(-(1/2)). In the case of a composite hypothesis, the best that it was
      possible to show is that the rate of convergence cannot be slower than that of
      the order of n(-(1/2)) ln n.

PMID- 16592223
TI  - Inequalities in fourier analysis on R.
AB  - THIS NOTE DESCRIBES TWO RESULTS: (i) a sharp Hausdorff-Young inequality for the
      Fourier transform on L(p)(R(n)) which extends an earlier result of Babenko; and
      (ii) a sharp form of Young's inequality for the convolution of functions on R(n).
      That is, best possible constants are obtained for the following L(p)(R(n))
      inequalities: [Formula: see text].

PMID- 16592224
TI  - On the homology of congruence subgroups and k(3)(z).
AB  - Let Gamma(n;p) be the congruence subgroup of SL(n;Z) of level p. We study the
      homology and cohomology of Gamma(n;p) as modules over SL(n;F(p)) and apply our
      results to obtain an upper bound for the order of K(3)(Z).

PMID- 16592225
TI  - The description of molecular structure.

PMID- 16592226
TI  - Properties of molten magnesium oxide.
AB  - The Significant Structure Theory of Liquids has been used to calculate the
      thermodynamic properties, viscosity, self-diffusion coefficient, and specific
      conductance of molten magnesium oxide, taking account of the decomposition of MgO
      to Mg and O(2) species in the gas-like part of the partition function.

PMID- 16592227
TI  - Gibberellic-Acid-induced cell elongation in lettuce hypocotyls.
AB  - Gibberellic acid (10 muM) causes lettuce hypocotyl cells to elongate by 400-500%
      more than water controls in 72 hr. Kinetic data indicate that whereas in water
      controls cell elongation occurs between 24 and 48 hr, in gibberellic-acid-treated
      material it starts at 8 hr and continues to 72 hr. Dry weight of the cell wall
      shows a corresponding increase with cell elongation. Two-hour pulse labeling with
      [(14)C]glucose, however, indicates a peak in the incorporation of label in the
      wall fraction at 8 hr, when growth has only just begun, and a progressive decline
      later, when elongation is occurring at maximum rate. The peak coincides with
      extensive dictyosomal activity, proliferation of endoplasmic reticulum and
      polyribosomes, and connections between the endoplasmic reticulum and plasmalemma
      in both water- and gibberellic-acid-treated hypocotyls. At later times, the cells
      contain only a thin layer of cytoplasm and no special cytological features are
      observed. These observations indicate that, although cell growth in lettuce
      hypocotyls is accompanied by wall synthesis, nevertheless the cells undergo their
      most rapid polysaccharide and protein synthesis prior to extension growth. They
      also explain the earlier reported "enhanced sensitivity" of lettuce hypocotyls to
      gibberellic acid application at 8 hr after the beginning of the experiment.

PMID- 16592228
TI  - Evolution of social behavior through interpopulation selection.
AB  - Under certain special conditions natural selection can be effective at the level
      of local populations, or demes. Such interpopulation selection will favor
      genotypes that reduce the probability of extinction of their parent population
      even at the cost of a lowered inclusive fitness. Such genotypes may be
      characterized by altruistic traits only in a viscous population, i.e., in a
      population in which neighbors tend to be closely related. In a non-viscous
      population the interpopulation selection will instead favor spiteful traits when
      the populations are susceptible to extinction through the overutilization of the
      habitat, and cooperative traits when it is the newly established populations that
      are in the greatest danger of extinction.

PMID- 16592229
TI  - Abiotic, Graphitic Microstructures in Micaceous Metaquartzite about 3760 Million
      Years Old from Southwestern Greenland: Implications for Early Precambrian
      Microfossils.
AB  - An Early Precambrian micaceous metaquartzite subjected to low to moderate
      metamorphism in the Isua area of Southwestern Greenland was derived from the
      erosion of preexisting rocks which were probably sialic in composition. This
      metaquartzite may have been formed before the emergence of life. It contains
      globular particles of graphite arranged in narrow veins or along foliation or
      bedding planes. This rock contains no organic compounds besides traces of methane
      and no biologically significant elements associated with the graphite
      microstructures. Reaction of primitive methane with ferric oxides appears to have
      oxidized the methane to the vein graphite and reduced the ferric oxides to
      ferrous-ferric oxide (magnetite). The graphitic microstructures are likely to be
      abiotic in origin, although a biological origin is not impossible. Somewhat
      younger microstructures found in other locations on earth have often been
      described as microfossils; this origin should be reexamined on the basis of the
      above mentioned conclusions.

PMID- 16592230
TI  - X and y operators for general linear transport processes.
AB  - This note presents the derivation of generalized Ambartsumian-Chandrasekhar X and
      Y functions for stationary transfer in a plane-parallel slab. An algebraic
      formula relating these functions to the usual reflection function is also
      presented, together with the appropriate generalization of the Chandrasekhar H
      equations for the semi-infinite medium. The planetary problem will also be
      briefly discussed.

PMID- 16592231
TI  - On a variational formula for the principal eigenvalue for operators with maximum
      principle.
AB  - In this paper a variational formula is obtained for the principal eigenvalue for
      operators with maximum principle. This variational formula does not require the
      operators to be self-adjoint. But if they are self-adjoint this formula reduces
      to the classical Rayleigh-Ritz formula.

PMID- 16592232
TI  - Genetic control of endosperm amylase activity and gibberellic Acid responses in
      standard-height and short-statured wheats.
AB  - In contrast to standard-height wheat genotypes, short-statured wheats having
      major genes for dwarfness do not show increased seedling growth after treatment
      with gibberellic acid. Endogenous gibberellic acid induces synthesis of amylase
      in the endosperm of germinating seeds, but the amount of amylase synthesized is
      greatly increased by exogenous gibberellic acid treatment in standard-height and
      in short-statured wheats that have dwarfing genes from the variety "Norin 10."
      "D6899," which has the "Tom Thumb" gene for height reduction, had about one
      fourth of the amylase activity of standard-height and Norin 10-derived, short
      statured wheats. This genotype showed little or no increased amylase activity
      after gibberellic acid treatment. Genetic analyses showed that the amount of
      amylase synthesized was controlled by a single gene and was dependent on the
      number of copies of the structural gene present in the endosperm. Dwarfism in
      wheat may be related to a blockage in gibberellic acid utilization because other
      workers have found that the amount of endogenous amylase synthesized in Norin 10
      derived, short-statured wheats is not growth-limiting, but it is not known if low
      amylase synthesis is related to dwarfism in the Tom Thumb derivative. No
      recombinants were recovered in a small population, suggesting that the Tom Thumb
      gene may pleiotropically affect plant height and the lack of response to
      gibberellic acid in amylase synthesis and seedling growth.

PMID- 16592233
TI  - Computer simulation of the toroidal equilibrium and stability of a plasma in
      three dimensions.
AB  - A computer program has been written to solve the equations for sharp boundary
      magnetohydrodynamic equilibrium of a toroidal plasma in three dimensions without
      restriction to axial symmetry. The numerical method is based on a variational
      principle that indicates whether the equilibria obtained are stable. Applications
      have been made to Tokamak, Stellarator, and Scyllac configurations.

PMID- 16592234
TI  - Evolutionary Changes in the Mating System of an Experimental Population of Barley
      (Hordeum vulgare L.).
AB  - An analysis is presented of the reproductive cycle in an experimental population
      of barley. The experimental design included growing three different generations
      of the population in the same year and environment, thus permitting an assessment
      of the mating system at three stages in the evolutionary history of the
      population, unconfounded by environmental differences. Gene frequencies sometimes
      differed significantly in adults and in the effective pollen pool. It was also
      found that out-crossing rate more than doubled during the twenty generations
      spanned by the study. These results provide evidence for selection during
      reproductive phases of the life cycle. They also demonstrate that evolution in
      this predominantly self-pollinating population was in the direction of increased
      recombinational potential.

PMID- 16592236
TI  - Almost All Roots of zeta(s) = a Are Arbitrarily Close to sigma = 1/2.
AB  - Let s = sigma + it. For any complex a, all but O(1/log log T) of the roots of
      zeta(s) = a in T < t < 2T lie in|sigma - 1/2| < (log log T)(2)/log T. The results
      extend easily to other functions satisfying a functional equation such as the
      Dirichlet L-functions, the Lerch functions, etc.

PMID- 16592235
TI  - Theory of rate processes and the compensation rule.
AB  - The rate of intermolecular charge transfer as involved in the theory of rate
      processes is derived for a quadratic generalization of Holstein's one-dimensional
      linear polaron theory. The activation energy and the activation entropy are shown
      to be proportional to the number of vibrational degrees of freedom associated
      with each molecular site. The activation entropy is found to be negative in this
      model, thus decreasing the reaction rate. A spin-polaron model is introduced
      where the electron is coupled in a specific way to N spins at each site. In this
      model both the activation parameters are positive and are proportional to N.
      Thus, the oscillator model gives a negative and the spin model gives a positive
      compensation temperature.

PMID- 16592237
TI  - Interwining operators and automorphic forms for the metaplectic group.
AB  - The local results announced in this paper concern the analytic continuation of
      interwining operators for the metaplectic covering group of SL(2) over an
      arbitrary local field and the decomposition of Weil's representation attached to
      the quadratic form q(x) = x(2). The global results concern Eisenstein series on
      the metaplectic group and a Siegel-Weil type formula relating the residues of
      these series to certain generalized theta functions.

PMID- 16592238
TI  - "Spshing noise": biological significance of its attraction and nonattraction by
      birds.
AB  - Many New World passerine birds, especially migrants which join mixed flocks of
      local species in the Neotropics, are attracted to a noise termed "spshing" used
      by humans to attract birds into view. The noise is effective because it mimics
      the vocalizations of certain bird species which play a central bonding role in
      mixed species flocks. Migrants join these flocks to gain local expertise about
      food sources and/or potential enemies in unfamiliar environments. Old World
      passerine migrants do not react to "spshing." In Africa, they do not join mixed
      flocks of local species because of more favorable environmental conditions
      negating the need to do so. In tropical Asia, many migrants join mixed flocks but
      the local bonding species give vocalizations unlike those of their counterparts
      in the Neotropics, and thus not like "spshing."

PMID- 16592239
TI  - On equimultiple subvarieties of algebroid hypersurfaces.
AB  - We deal with a finite projection piv of a hypersurface V in (r + 1)-space onto an
      affine r-space A(r) and with the critical variety Delta of piv in A(r). We show
      that if Delta is equimultiple along a smooth subvariety W(0), then W(0) admits a
      unique lifting to a subvariety W of V (necessarily isomorphic to W(0)) and that
      also V is then equimultiple along W.

PMID- 16592240
TI  - Theory of homogeneous dynamos in a rotating liquid sphere.
AB  - A spherical harmonic analysis is made of the hydrodynamic equation governing the
      flow of an incompressible liquid in a rotating sphere in the presence of the
      magnetic Lorentz force. Nonlinear partial differential equations are derived for
      the functions S(n)(r,t) and T(n)(r,t) entering the spherical harmonic
      representation of the velocity field.

PMID- 16592241
TI  - Photoassisted electrolysis of water by irradiation of a titanium dioxide
      electrode.
AB  - Ultraviolet irradiation (351, 364 nm) of the n-type semiconductor TiO(2) as the
      single crystal electrode of an aqueous electrochemical cell evolves O(2) at the
      TiO(2) electrode and H(2) at the Pt electrode. The gases are typically evolved in
      a two: one (H(2):O(2)) volume ratio. The photoassisted reaction seems to require
      applied voltages, but values as low as 0.25 V do allow the photoassisted
      electrolysis to proceed. Prolonged irradiation in either acid or base evolves the
      gaseous products in amounts which clearly demonstrate that the reaction is
      catalytic with respect to the TiO(2). The wavelength response of the TiO(2) and
      the correlation of product yield and current are reported. The results support
      the claim that TiO(2) is a true photoassistance agent for the electrolysis of
      water. Minimum optical storage efficiencies of the order of 1% can be achieved by
      the production of H(2).

PMID- 16592242
TI  - Gross thermodynamics of heat engines in deep interior of Earth.
AB  - From the gross conservation laws of thermodynamics in a convecting material we
      derive a bound on the ratio of the rate of production of mechanical or magnetic
      energy to the rate of internal radioactive heating which drives the convection.
      Our bound for this "efficiency" depends on the temperatures in the material, and
      can exceed unity. Whether the bound can be attained by "efficiencies" in real
      fluids is not known, but a simple machine shows that "efficiencies" larger than
      unity are physically realizable. Our bound gives upper limits on the viscous
      dissipation in the earth's mantle and ohmic heating in the core, but these limits
      are too large to be physically interesting.

PMID- 16592243
TI  - Source theory discussion of deep inelastic scattering with polarized particles.
AB  - A general phenomenological framework is provided for the discussion of the
      inelastic scattering of polarized electrons (muons) on polarized nucleons, when
      regarded as the absorption of polarized virtual photons. The relevant cross
      sections compare parallel and antiparallel orientations of the photon helicity
      and nucleon spin, and also deal with linear combinations of longitudinal and
      transverse polarization. The polarization asymmetry for transverse polarization,
      P, assumes a scaling form in the deep inelastic scattering region, and should go
      to zero as omega(-1) for large omega. The latter behavior is connected, through
      the use of the improved scaling variable omega(s), with the high energy real
      photon situation. A sum rule is exhibited which implies that P must change sign
      in the deep inelastic region. This sum rule also yields the known Drell-Hearn sum
      rule for real photon Compton scattering, when combined with another, new, sum
      rule for the anomalous magnetic moment. The latter is verified in the context of
      pure electrodynamics to the lowest order in alpha. Finally, it is conjectured
      that P specifically changes from negative to positive values as omega varies from
      1 to infinity.

PMID- 16592244
TI  - On some periodic toda lattices.
AB  - A discrete version of Floquet's theory is developed and applied to a system of
      non-linear differential equations related to the periodic Toda lattice. A special
      solution previously found by Toda is thus seen to fit into the formalism of
      inverse scattering problems.

PMID- 16592245
TI  - On the possibility of a hydrodynamic model of the electron.
AB  - We explore the possibility that the mutual repulsive forces of a uniformly
      charged sphere could be kept in balance dynamically by a steady circulation of
      the material, which is assumed to be a nonconducting perfect fluid of uniform
      density. An exact solution is obtained of Maxwell's equations and of the
      hydrodynamic equations in the nonrelativistic approximation, which satisfies the
      boundary conditions on the surface of the sphere. In this solution all the
      components of the velocity and of the magnetic field are found to vanish on the
      surface, but not the electric field. The pressure can also be made to vanish on
      the surface, but in the interior it turns out to be negative, which makes the
      present solution unacceptable.

PMID- 16592246
TI  - Connectivities R(i) of Frechet Spaces in Variational Topology.
AB  - A global study of geodesics, joining points A(1) [unk] A(2) on a Riemannian
      manifold N(n), is oriented by the answers given to two questions. How does the
      concept of a nondegenerate geodesic enter, and what topological invariants best
      condition the geodesics joining A(1) to A(2)? We answer the first question by
      defining and exploiting nondegenerate point pairs A(1) [unk] A(2) on N(n). The
      connectivities R(i) of M(n) used in ordinary critical point theory should be
      replaced by the connectivities R(i) of the pathwise components of the Frechet
      metric space [unk](A(1) ) (A(2) ) defined in this paper. These components are
      homeomorphic. Their connectivities R(i) condition the geodesics joining A(1) to
      A(2) on N(n) in a way to be disclosed. Detailed proofs are found in the
      references listed, or will be presented later.

PMID- 16592247
TI  - Concerning jahn-teller effects.
AB  - Jahn-Teller effects are grouped into two categories. The first arises from
      incomplete shells of degenerate orbitals. It includes the first-order Jahn-Teller
      effect, and the pseudo Jahn-Teller effect. The second arises from filled and
      empty molecular orbitals that are close in energy, and is the second-order Jahn
      Teller effect. The two categories have quite different physical bases. As a
      result, geometric distortions produced by the first are quite small and normally
      lead to dynamic effects only. In favorable cases, the second-order Jahn-Teller
      effect produces very large distortions, including complete dissociation of a
      molecule. This can occur even when the relevant molecular orbitals are separated
      in energy by as much as 4 eV.

PMID- 16592248
TI  - Species richness of the parasitic fungi of british trees.
AB  - The species richness of fungi associated with British trees is described by a
      significant species/area curve (r = 0.53, 0.01 > P > 0.001). Introduced tree
      species cannot be shown to have fewer fungal species than natives, per unit
      distributional range about Britain. Also, among natives and among introductions,
      older host taxa do not have more fungal species than do younger ones. This
      indicates the species richness of fungi to rapidly reach the limit set by host
      range, within ecological time. The slope of the species/area relationship for
      fungi is one-fourth that for insects; we propose that this is due to the
      inherently greater dispersability of fungi. Finally, the species/area regression
      residuals for fungi are correlated with those for insects (r = 0.65, 0.001 > P),
      suggesting plant defense mechanisms may be generally effective to plant
      parasites, be they insects or fungi.

PMID- 16592249
TI  - Satellite-rich DNA in cucumber: hormonal enhancement of synthesis and subcellular
      identification.
AB  - Cucumber hypocotyl DNA in neutral CsCl distributes into a mainband comprising 59%
      of the total, and two large satellite bands which contribute 41% to the DNA
      pattern. Organelle enrichment studies show that the densities of mitochondrial
      and chloroplast DNA coincide with those of the satellite bands. At least 12-19%
      of total cucumber DNA is associated with the cytoplasmic organelles. These
      values, which are several times larger than those usually quoted for higher
      plants, are correlated with an unusually low amount of DNA per haploid nucleus in
      cucumber. Synthesis of the satellite DNAs, as well as mainband DNA, is
      appreciably stimulated in vivo by application of the plant hormone, gibberellin.
      Endogenous and hormone-enhanced synthesis of the satellite DNAs is
      proportionately greater in target tissue showing a high rate of organelle
      synthetic activity.

PMID- 16592250
TI  - An algebraic description of stereochemical correspondence.
AB  - It is shown that a stereochemical correspondence between two molecular systems
      can be represented by a commuting diagram of the point groups and permutation
      groups involved. The effect of the diagrammatic condition on the mappings of the
      cosets, double cosets, subgroup lattice, and double coset algebra determined for
      the two molecular systems by point group to permutation group homomorphisms is
      detailed. Chemical similarities implied by a stereochemical correspondence are
      indicated, and six examples are provided and discussed.

PMID- 16592251
TI  - Potential for nitrogen fixation in maize genotypes in Brazil.
AB  - N(2) fixation in field-grown maize (Zea mays L.) plants was estimated by a
      nondestructive acetylene reduction method which permitted the plants to continue
      growing and produce seeds. Samples from six areas revealed mean nitrogenase
      activities of 74-2167 nmol of C(2)H(4)/(g of dry roots x hr) for 10 plants. Among
      276 S(1) lines planted in two field experiments, 17 lines were selected for
      further nitrogenase activity assays after prescreening. Variability within lines
      was high but significant differences among lines were obtained in one experiment.
      The best lines showed mean nitrogenase activities of 2026, 2315, and 7124 nmol of
      C(2)H(4)/(g of dry roots x hr), whereas the original cultivar reduced only 313
      nmol. The highest value approaches the nitrogenase activity of soybean. If the
      theoretical 3:1 (C(2)H(4)/N(2) reduced) conversion factor is used, a potential
      daily N(2) fixation of 2 kg of N(2)/hectare can be calculated. Periodic sampling
      within a brachytic maize cultivar revealed that maximum nitrogenase activity
      occurred at about the 75% silking stage. Soil effects also were pronounced. N(2)
      fixing Spirillum sp. could be isolated from all active root pieces when they were
      surface sterilized. These organisms appear to be primarily responsible for root
      nitrogenase activity in maize.

PMID- 16592252
TI  - Circadian Rhythm of Neuron R15 of Aplysia californica: In Vivo Photoentrainment.
AB  - (1) The neuron R15 in the parietovisceral ganglion of Aplysia has a circadian
      rhythm of spiking activity when recorded in the isolated ganglion. The rhythm is
      entrained in vivo by light-dark cycles. (2) The phase of the R15 rhythm is a
      function not only of the entraining light schedule, but also of the time of
      dissection. Changes in the dissection time during the light portion of the light
      dark cycle yield little change in the subsequent R15 peak time. Dissections
      during the dark portion produce peak times that vary with dissection time with a
      slope that is approximately one. (3) The circadian rhythm of R15 can be phase
      shifted in vivo by changes in the phase of the entraining light-dark cycle in one
      to two weeks. R15 neurons of blinded Aplysia, however, show little or no phase
      shift in this time. (4) It is concluded that the eyes are important as receptors
      for the photoentrainment of the R15 rhythm in vivo, but that neural connections
      from the eyes to R15 are not required.

PMID- 16592253
TI  - Pseudoconformal geometry of hypersurfaces in C.
AB  - The pseudoconformal geometry (CR structure) of a real hypersurface M in C(n+1) is
      reviewed. We give an alternative formulation of a theorem of Cartan-Tanaka-Chern
      on the existence of a unique normalized Cartan connection on a principal bundle Y
      over M. A family of curves defined by this connection, called chains, is shown to
      be the projection of light rays of a conformal equivalence class of Lorentz
      metrics on a trivial circle bundle over M. The simply connected homogeneous
      manifolds locally CR equivalent to the sphere are classified. A theorem on moduli
      for deformations of the complex structure on the ball in C(n+1) is given.

PMID- 16592254
TI  - Singular Integrals and the Principal Series, IV.
AB  - The intertwining operators that have been constructed for all the series of
      unitary representations appearing in the Plancherel formula of a connected real
      semisimple Lie group of matrices are given a new normalization and then applied
      in two ways. The first is to obtain dimension formulas for the commuting algebras
      of the unitary representations in question. The second is to establish the
      existence of complementary series. These bear the same relationship to the
      unitary representations under study that the complementary series found earlier
      bear to the principal series.

PMID- 16592255
TI  - Observational validation of the chronometric cosmology: I. Preliminaries and the
      redshift-magnitude relation.
AB  - Results of comprehensive observational tests of the cosmological theory proposed
      by Segal in 1972 are summarized in this and succeeding notes. Within a framework
      of natural and general causality and symmetry considerations, the theory is
      mathematically essentially unique. It implies definite relations between directly
      observed quantities (redshift, apparent magnitude and diameter, number counts,
      and the like) which are entirely free of adjustable parameters, such as the q(0)
      and Lambda of general relativistic cosmologies. Rigorous statistical analysis of
      large ( greater, similar100) or systematically defined samples of galaxies or
      quasars accepts these relations at substantial probability levels. Note I
      establishes uniform statistical procedures and compares the redshift-magnitude
      relations of major samples with the theoretical relations of the present and
      expansion theories.

PMID- 16592256
TI  - Iron-sulfur clusters II: Kinetics of ligand exchange studied on a water-soluble
      Fe(4)S(4)(SR)(4) cluster.
AB  - The water-soluble tetranuclear iron-sulfur cluster ion Fe(4)S(4)(SCH(2)CH(2)CO(2)
      (-))(4) (6-) (II) has been prepared. The stability of II in water is sufficient
      to allow the spectrotitrimetric determination of the pK(a) of its Fe(4)S(4) core
      as 7.4. In our hands the one-electron reductions of compounds I [Fe(4)S(4)(SR)(4)
      (2-), R = alkyl or aryl,] are thermodynamically irreversible with associated
      E(1/2) values greater than those for one-electron reduction of ferredoxins. In
      contrast, the one-electron reduction of II is thermodynamically reversible and
      the associated potential (-0.58 V versus hydrogen electrode) approaches closely
      that of the ferredoxins. The kinetics for ligand exchange of II as a function of
      pH and thiol concentration are in accord with four reversible mercaptan/lyate
      species exchange reactions followed by product formation via specific acid and
      base catalysis. Preliminary experiments indicate the nucleophilic order towards
      II to be Cl(-) [unk] Br(-) < HO(-) < CN(-).

PMID- 16592257
TI  - Paleopleurocapsa wopfnerii gen. et sp. nov.: A Late Precambrian alga and its
      modern counterpart.
AB  - Silicified dolomite of the approximately one billion year old Skillogalee
      Dolomite of the Adelaide Geosyncline, South Australia, contains organically
      preserved microfossils of a structurally complex, crustose pleurocapsalean
      cyanophyte, herein described as Paleopleurocapsa wopfnerii. Although actual cell
      contents have been degraded, lamellar sheath material faithfully preserves the
      morphology of the alga. Comparison with specimens of the modern genus Pleurocapsa
      Thuret demonstrates affinities at the family level and quite possibly even
      generic identity.

PMID- 16592258
TI  - Dedekind's eta-function and the cohomology of infinite dimensional Lie algebras.
AB  - We compute the cohomology of certain infinite dimensional Lie algebras which are
      subalgebras of Lie algebras introduced by Moody and Kac. We note a relation
      between our results and the cohomology of loop spaces of compact groups. Finally,
      we derive, by Euler-Poincare, identities of Macdonald for powers of the Dedekind
      eta-function.

PMID- 16592259
TI  - Well-posed inverse spectral problems.
AB  - It is known that if complete spectral data are provided, the potential function
      in a Sturm-Liouville operator is uniquely determined almost everywhere. If two
      such operators have spectra that differ in a finite number of eigenvalues, then
      the corresponding potential functions will no longer be the same. However, as is
      demonstrated when the nonidentical eigenvalues are almost equal, then the
      corresponding potential functions will also be nearly equal almost everywhere.
      Furthermore, if an operator and its spectrum are given and the potential is
      presumably known and if a second operator is defined in such a way such that its
      eigenvalues agree with the eigenvalues of the first operator except for a finite
      set, then the potential corresponding to the second operator can be explicitly
      found by solving a set of nonlinear ordinary differential equations. Lastly, it
      is shown that the procedures discussed here and the Gelfand-Levitan procedures
      are significantly different, and in fact that the Gelfand-Levitan procedure is
      almost certainly not well posed.

PMID- 16592261
TI  - National Science Foundation: Origins, hopes, and aspirations.

PMID- 16592260
TI  - Infinitesimal generators and quasi-units in potential theory.
AB  - The underlying structure is taken as a strongly superharmonic cone [unk], defined
      as a partially ordered abelian semigroup with identity 0 which admits a
      multiplication by nonnegative scalars and satisfies two fundamental axioms of a
      potentialtheoretic character. In terms of a fixed nonzero element e there is
      introduced on [unk] a one-parameter family of nonlinear operators S(lambda)
      (lambda >/= 0) closely connected with the abstract theory of quasibounded and
      singular elements. The semigroup {S(lambda)} admits an infinitesimal generator A,
      and the elements invariant under A, called quasi-units, generalize the Yosida
      quasi-units in the theory of Riesz spaces. Quasi-units in [unk] are studied, both
      from a potentialtheoretic and a function-alanalytic viewpoint, culminating in a
      spectral representation theorem for quasi-bounded elements which extends the
      classical Freudenthal spectral theorem of Riesz space theory.

PMID- 16592262
TI  - A foundation for research.

PMID- 16592263
TI  - Whither NSF?-The higher derivatives.

PMID- 16592264
TI  - A topological theorem for nonlinear dynamics in chemical and ecological networks.
AB  - A topological theorem is given which places restrictions on the numbers and types
      of critical points in nonlinear chemical and ecological systems, provided certain
      stringent conditions on the flows on the boundary of the concentration space are
      satisfied. The sets of critical points that are found for stable and unstable
      oscillations, and for competitive exclusion, represent the simplest sets of
      critical points that satisfy the topological theorem. The restrictions that are
      imposed on bifurcations of the dynamics are discussed.

PMID- 16592265
TI  - Reaction of tris(bipyridine)ruthenium(III) with hydroxide and its application in
      a solar energy storage system.
AB  - Irradiation of Ru(bipy)(3) (2+) (bipy = 2,2'-bipyridine) with light below 560 nm
      results in the formation of a charge-transfer excited state potentially capable
      of reducing water to dihydrogen with concomitant production of Ru(bipy)(3) (3+).
      The latter may be reduced by hydroxide [Formula: see text] to form dioxygen and
      regenerate the starting complex. The use of these reactions in a cell designed to
      bring about the photochemical decomposition of water is proposed.The
      stoichiometry, kinetics, and mechanism of the Ru(bipy)(3) (3+)-hydroxide reaction
      have been investigated by conventional and stopped-flow spectrophotometry. The
      dioxygen yield is a sharp function of pH, attaining its maximum value (about 80%)
      at pH 9. At low pH (3 and 4.8) the production of ruthenium(II) is first order
      with k(obsd) = (1.41 +/- 0.04) x 10(-4) sec(-1) (25 degrees , ionic strength mu =
      1.00 M with sodium sulfate). In the intermediate pH range (7.9-10.0) complex
      kinetics are observed. In the hydroxide range 0.01-0.50 M, ruthenium(II)
      production is predominantly first order with k(obsd) = k(a)[OH(-)] + k(b)[OH(
      )](2) sec(-1); k(a) = 148 M(-1) sec(-1) and k(b) = 138 M(-2) sec(-1) (25 degrees
      , mu = 1.00 M, sodium sulfate). For the k(a) term, the activation parameters are
      DeltaH(double dagger) = 15.3 +/- 1.0 kcal mol(-1) and DeltaS(double dagger) = 7
      +/- 3 cal deg(-1) mol(-1) (1 cal = 4.184 J). An intermediate species (lambda(max)
      800 nm) forms at the same rate as ruthenium(II) in this hydroxide range. It
      disappears with k(obsd) = 1.2 + 1.1 x 10(2) [OH(-)] sec(-1) at 25 degrees .
      Similarly absorbing (lambda(max) 750 to 800 nm) species are generated by the
      addition of hydroxyl radical to M(bipy)(3) (2+/3+) [M = Fe(II), Os(II), Ru(II),
      Cr(III), Ru(III)] in pulse radiolysis experiments. The kinetics above pH 7 are
      described in terms of rate-determining nucleophilic attack by hydroxide on the
      bound bipyridine ring. The hydroxide adduct so generated is tentatively
      identified with that observed in the pulse radiolysis experiments with
      Ru(bipy)(3) (2+).For reduction of Ru(bipy)(3) (3+) by hydrogen peroxide
      ruthenium(II) production is first order with k(obsd) = k(c)[HO(2) (-)] +
      k(d)[H(2)O(2)] where k(c) = 5.4 x 10(7) M(-1) sec(-1) and k(d) = 8.3 M(-1) sec(
      1) (25 degrees , mu = 1.00 M, pH 3.5 to 9.7). This reaction produces dioxygen in
      83 +/- 15% yield at pH 6.8 and in 1.0 N sulfuric acid.

PMID- 16592266
TI  - The disjunction property implies the numerical existence property.
AB  - Any recursively enumerable extension of intuitionistic arithmetic which obeys the
      disjunction property obeys the numerical existence property. Any recursively
      enumerable extension of intuitionistic arithmetic proves its own disjunction
      property if and only if it proves its own inconsistency.

PMID- 16592267
TI  - A complete solution of the periodic Toda problem.
AB  - The motion of the periodic Toda lattice is explicitly determined in terms of
      Abelian integrals.

PMID- 16592268
TI  - General model for osmotic and pressure-induced flow in plant roots.
AB  - This paper presents a general model to describe coupled solute and water flow
      through plant roots when they are subjected to osmotic or hydrostatic pressure
      gradients, or both simultaneously. The model is based on well-established
      membrane transport equations derived from irreversible thermodynamic
      considerations. A variety of experimentally observed phenomena such as changes in
      root resistance with flow rate, apparent negative resistance effects, xylem sap
      dilution, and apparent non-osmotic water transport can be adequately explained
      with this model. The model also predicts that an exuding excised root system will
      be very insensitive to changes in the hydraulic conductivity coefficient.
      Previous work with a flat membrane of unit surface area and uniform properties is
      confirmed for a cylindrical coordinate system of nonuniform characteristics.

PMID- 16592269
TI  - Photooxidation of chlorins by quinones studied by nuclear magnetic resonance
      techniques.
AB  - The reactions of photo-excited chlorophylls and pheophytins with quinones have
      been investigated by nuclear magnetic resonance techniques. In slightly alkaline
      solutions the quinone signals showed line broadening which is explained by
      degenerate electron transfer between semiquinone radical ions and their
      benzoquinone parents. In neutral solutions, chemically induced dynamic nuclear
      polarization was observed which is ascribed to the pair, chlorophyll cation
      semiquinone anion. A kinetic analysis of the dependence of these effects upon the
      quinone concentration suggests that only the reactions of triplet-chlorophyll
      with the quinones give rise to chemically induced dynamic nuclear polarization
      effects.

PMID- 16592270
TI  - The triplet state in bacterial photosynthesis: Possible mechanisms of the primary
      photo-act.
AB  - In vitro and in vivo triplet state electron paramagnetic resonance (epr) spectra
      of bacteriochlorophylls (Bchls) show important differences in (a) electron spin
      polarization (esp), and (b) zero field splitting (ZFS) parameters. The unusual
      esp and ZFS properties of the observed in vivo triplet state are best interpreted
      as arising from a short-lived radical pair precursor (not directly observable by
      epr) formed in or with the special pair of bacteriochlorophyll molecules involved
      in the primary photo-act.

PMID- 16592271
TI  - The characters of the holomorphic discrete series.
AB  - This paper summarizes the derivation of an explicit and global formula for the
      character of any holomorphic discrete series representation of a reductive Lie
      group G which satisfies certain conditions. The only very restrictive condition
      is that G/K be a Hermitian symmetric space. (Here K is the maximal compact
      subgroup of G.).

PMID- 16592272
TI  - An inequality among determinants.
AB  - WE PROVE THAT FOR ANY TRACE CLASS OPERATORS, [FORMULA: see text].

PMID- 16592273
TI  - Exhaustion functions and Stein neighborhoods for smooth pseudoconvex domains.
AB  - A strictly plurisubharmonic exhaustion function with negative values is
      constructed for arbitrary relatively compact pseudoconvex domains with smooth
      boundary in a Stein manifold. It is applied to verify the Serre conjecture in a
      special case. A sufficient condition is given that guarantees the existence of a
      neighborhood-basis of Stein domains for certain bounded pseudoconvex domains on a
      Stein manifold.

PMID- 16592274
TI  - Some fundamental groups in the arithmetic of algebraic curves over finite fields.
AB  - Associated with some systems of unramified coverings of algebraic curves over
      finite fields there are spaces analogous to the universal covering transformation
      spaces. These spaces have also arithmetic features; they represent all the
      Frobeniuses in the systems. This theory can be applied to the reduction mod [unk]
      of the Shimura curves.

PMID- 16592275
TI  - Spectra of convolution operators on L spaces.
AB  - Let 1 < p < infinity with p not equal 2. Let G denote the n-torus or Euclidean n
      space, and let Gamma be the dual group of G. We show the existence of a
      multiplier transformation T on L(p)(G) which satisfies the following properties:
      (a) the transform T of T is smooth and vanishes at infinity on Gamma; (b) the
      spectrum of T on L(p) properly contains T(Gamma) union or logical sum{0}.

PMID- 16592276
TI  - Necessary and sufficient conditions for solvability of the Lewy equation.
AB  - We find the necessary and sufficient conditions for the local solvability of
      Lewy's equation, ([unk]/[unk]z + iz [unk]/[unk]t) u = f. If R(3) is realized as
      the boundary of the generalized "upper-half-space" in C(2), then the conditions
      are, near a point P [unk] R(3), the analytic continuability of the Cauchy-Szego
      integral of f past P. In case the sufficient condition is satisfied, solutions
      are found that satisfy optimal regularity properties. Various generalizations are
      also given.

PMID- 16592277
TI  - Anticytokinin activity of substituted pyrrolo[2,3-d]pyrimidines.
AB  - Ten substituted pyrrolo[2,3-d]pyrimidines were tested as cytokinins and
      anticytokinins in the tobacco bioassay. Eight new anticytokinins were identified
      and two were found to be highly active. The most potent species were 4
      cyclohexylamino- and 4-cyclopentylamino-2-methylthiopyrrolo[2,3-d]pyrimidine, of
      which 0.05 and 0.009 muM concentrations, respectively, were required to produce
      detectable inhibition of the growth of tobacco callus cultured on a medium
      containing 0.003 muM 6-(3-methyl-2-butenylamino)purine. The inhibition of growth
      by moderate (</=6.6 muM) concentrations of these compounds was reversible by
      equal or higher concentrations of 6-(3-methyl-2-butenylamino)purine, but not by
      indole-3-acetic acid or gibberellic acid. These substituted pyrrolo[2,3
      d]pyrimidines were also found to enhance bud formation at high cytokinin
      concentrations, suggesting that a cytokinin may act at more than one cellular
      site in exerting its growth-promoting and morphogenetic effects.

PMID- 16592278
TI  - Solar abundance of platinum.
AB  - Three lines of neutral platinum, located at lambda 2997.98 A, lambda 3064.71 A,
      and lambda 3301.86 A have been used to determine the solar platinum abundance by
      the method of spectral synthesis. On the scale, log A(H) = 12.00, the thus
      derived solar platinum abundance is 1.75 +/- 0.10, in fair accord with Cameron's
      value of log A(Pt) = 1.69 derived by Mason from carbonaceous chondrites and
      calculated on the assumption that log A(Si) = 7.55 in the sun.

PMID- 16592279
TI  - Valence-bond theory of compounds of transition metals.
AB  - An equation relating the strength (bondforming power) of an spd hybrid bond
      orbital to the angles it makes with other bond orbitals is formulated and applied
      in the discussion of the structures of transition-metal carbonyls and other
      substances by the valence-bond method. The rather simple theory gives results
      that agree well with those obtained by the complicated and laborious calculation
      of sets of orthogonal hybrid bond orbitals with maximum strength.

PMID- 16592280
TI  - Absence of interference in photoexcitation of triplets.
AB  - Kinetics of growth and decay of triplet states of molecules at known orientation
      in a magnetic field have been measured. Amplitudes of the zero field eigenstates
      in each of the eigenstates at finite field were varied by choice of orientation.
      No interference between the amplitudes of the zero field states was found in the
      observed kinetics. It is concluded that excitations into the individual zero
      field components proceed via independent channels.

PMID- 16592281
TI  - Collisional energy transfer and quenching of electronic excitation.
AB  - The purpose of this paper has been to explore in a preliminary way the nature and
      mechanism of collisional energy transfer and quenching of electronic excitation.
      For this purpose, the Born approximation has been used, and the triplet-triplet
      and singlet-singlet transfer, and the triplet-triplet and singlet-singlet
      quenching have been studied. It has been shown theoretically that (i) the singlet
      singlet transfer constants (or cross sections) are always larger than the triplet
      triplet transfer constants (or cross sections) for the same system of donor and
      acceptor; (ii) for the singlet-singlet transfer, the observed cross section
      varies linearly with respect to the spectral overlap between the donor emission
      and the acceptor absorption; (iii) the reason that the quenching constants (or
      cross sections) are always smaller than the energy transfer constants (or cross
      sections) is due to the fact that for the quenching the vibration of the acceptor
      hardly participates in accepting the electronic excitation and for the energy
      transfer only part of the excited electron energy of the donor is converted into
      the energy of nuclear motion; and (iv) the polar acceptor molecules are better
      quenchers than nonpolar acceptor molecules.

PMID- 16592282
TI  - Limits of zeroes of recursively defined polynomials.
AB  - Let {P(n)(z)} be a sequence of polynomials satisfying a linear homogeneous
      recursion whose coefficients are polynomials in z. Necessary and sufficient
      conditions are found, subject to mild nondegeneracy conditions, that a number x
      be a limit of zeroes of {P(n)} in the sense that there is a sequence {z(n)} with
      P(n)(z(n)) = 0, z(n)-->x. An application is given to a family of polynomials
      arising in a map-coloring problem.

PMID- 16592283
TI  - On complexifications of real manifolds.
AB  - This paper studies the problem of obtaining complexifications of a differentiable
      manifold which have desirable analytic or algebraic properties and which are
      minimal in the sense described below. It is seen that there is a significant
      difference between analytic and algebraic complexifications.

PMID- 16592284
TI  - Pion spectrum in decay of Psi'(3.7) to Psi(3.1).
AB  - The decay of Psi' --> Psi + pipi is described by a chiral epsilon model. The
      general features of the observed dipion spectrum are well reproduced. Comparison
      with the hadronic decay rho' --> rho + pipi indicates that the Psi'Psiepsilon
      coupling is relatively suppressed by a factor approximately 10(-2).

PMID- 16592285
TI  - Absence of an intracellular cobalamin-binding protein in cultured fibroblasts
      from patients with defective synthesis of 5'-deoxyadenosylcobalamin and
      methylcobalamin.
AB  - Three distinct classes of human mutations (cbl A, cbl B, and cbl C) cause
      defective synthesis of cobalamin (Cbl; vitamin B(12)) coenzymes. Cultured
      fibroblasts from that unique class (cbl C) deficient in the synthesis of both Cbl
      coenzymes, 5'-deoxyadenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), were
      used to explore the underlying defect. We compared the uptake of transcobalamin
      II(TC II)-bound cyano[(57)Co]cobalamin (CN-Cbl) by cbl cells with that of other
      control and mutant cell lines. Although the cbl C cells initially took up CN
      [(57)Co]Cbl normally, they were unable to retain it. To characterize this "leak"
      further, cell extracts were prepared following incubation and chromatographed on
      Sephadex G-150. After incubations of 1-2 hr, most of the CN-[(57)Co]Cbl
      accumulated by control cells was still bound to TC II; the remainder was free.
      Thereafter, an ever-increasing fraction of the labeled Cbl eluted with an
      intracellular cobalamin-binding protein (ICB); more than 80% of the total was so
      bound after 76 hr incubations. ICB had an apparent molecular weight similar to
      that of several Cbl "R" binders (about 120,000), but was distinguished from them
      by its failure to react with specific anti-"R"binder antiserum. Significantly, no
      ICB was detected in extracts of three different cbl C lines even aftr prolonged
      incubations, whereas its appearance in cbl A, cbl B, and mutase apoenzyme mutants
      was normal. We propose: that ICB is required for retention of cobalamins by
      cells; and that cbl C cells "leak" cobalamins and show defective synthesis of Cbl
      coenzymes because they lack this intracellular binder.

PMID- 16592286
TI  - Trophic radiation through polymorphism in cichlid fishes.
AB  - Several morphologically defined species of cichlid fishes (Cichlasoma) endemic to
      the Cuatro Cienegas basin of Mexico and differing in tooth structure, body shape,
      and diet are allelically identical at 27 gene loci. The presence of only one
      Mendelian population in each of three drainage systems studied and the occurrence
      of two of the morphotypes in the same broods indicate that the supposed species
      are morphs. That trophic radiation in the Cuatro Cienegas cichlids has been
      achieved through ecological polymorphism rather than speciation raises questions
      regarding the genetic basis for the extensive intralacustrine radiation of
      cichlids in Africa and elsewhere.

PMID- 16592287
TI  - Isolation of mRNA coding for immunoglobulin heavy chain.

PMID- 16592288
TI  - Progress and prospects in high energy astrophysics.

PMID- 16592289
TI  - Phenomenological analysis of observed relations for low-redshift galaxies.
AB  - Maximum-likelihood estimates are made for the exponent p in the phenomenological
      redshift-distance relation z [unk] r(p) for galaxies at redshifts less,
      similar0.03, on the basis of redshift (z)-magnitude (m)-apparent diameter (theta)
      observations given in the Reference Catalogue of Bright Galaxies [de Vaucouleurs,
      G. & de Vaucouleurs, A. (1964)]. The estimates are in the range 1.96 </= p </=
      2.04 for the full sample of 742 galaxies having m - z - theta data, with
      dispersions less, similar0.08, and in a similar but broader range for various
      subsamples. Explicit allowance for an observational cut-off in apparent magnitude
      in the m - z relation reinforces the result that p approximately 2. Independent
      estimation based on a cut-off independent generalized Kafka-Schmidt V/V(m) test
      for a subsample in conservatively limited redshift and magnitude ranges, yields p
      = 2.05.

PMID- 16592290
TI  - A model for the hydrogen bond.
AB  - A MODEL OF THE LINEAR HYDROGEN BOND HAS BEEN DEVISED WHICH IS CHARACTERIZED BY
      THREE PHYSICAL PARAMETERS OF THE ISOLATED ELECTRON DONOR AND PROTON DONOR
      MOLECULES: mu(A-H), the bond dipole moment; DeltaI, the difference in ionization
      potential between that of the electron donor and the corresponding noble gas
      atom; and l, the length of the electron donor lone-pair of electrons. The model
      is able to explain dimerization energy, charge transfer, internuclear separation,
      directionality, stretching force constants, dimer dipole moment, and infrared
      intensity enhancement.

PMID- 16592291
TI  - Nonprevalence of biochemical fossils in kerogen from pre-Phanerozoic sediments.
AB  - Evidence of biochemical and geochemical evolution was sought in insoluble
      carbonaceous matter from 30 selected pre-Phanerozoic sediments ranging in age
      from about 3.8 to about 0.7 x 10(9) years. The carbon isotope ratios observed
      were in the range of -20 to -32 per mil with reference to the Peedee belemnite
      standard, similar to those previously reported. No systematic trends are obvious
      to us. Stepwise pyrolysis-gas-chromatography showed only molecules with fewer
      than 8 carbon atoms at the level of sensitivity of 10(-9) g of organics in a 10
      mg rock sample. Carbon, hydrogen, and nitrogen analyses showed noncarbonate
      carbon from less than 0.1% to more than 3%, with very small amounts of N. The H/C
      (atomic) ratios on HCl-leached and HF-treated samples were generally less than
      0.3. Evidence of low pyrolysis yields (micro-analysis) and low H/C atomic ratios
      (macro-analysis) implies that the carbonaceous solids in even the least
      metamorphosed of these ancient sediments have evolved far toward amorphous carbon
      or graphite and do not yield useful "biochemical fossils."

PMID- 16592292
TI  - A Bruhat decomposition for the loop space of a compact group: A new approach to
      results of Bott.
AB  - We give a new proof of Bott's result, that the loop space of a compact, simply
      connected, simple Lie group has a cellular decomposition of a certain type. In
      particular, one obtains the Poincare polynomial for the loop space and Bott
      periodicity for the unitary group.

PMID- 16592293
TI  - A theorem on the Schwartz space of a reductive Lie group.
AB  - The purpose of this paper is to define the Fourier transform of an arbitrary
      tempered distribution on a reductive Lie group. To this end we define a
      topological vector space, [unk](G), in terms of the classes of irreducible
      unitary representations of G, which plays role of a dual Schwartz space. Our main
      theorem then asserts that the usual L(2) Fourier transform, when restricted to
      functions in the Schwartz space, [unk](G) defined by Harish-Chandra, provides a
      topological isomorphism from [unk](G) onto [unk](G).

PMID- 16592294
TI  - Analysis of the subtractive algorithm for greatest common divisors.
AB  - The sum of all partial quotients in the regular continued fraction expansions of
      m/n, for 1 </= m </= n, is shown to be 6pi(-2)n(ln n)(2) + O(n log n(log log
      n)(2)). This result is applied to the analysis of what is perhaps the oldest non
      trivial algorithm for number-theoretic computations.

PMID- 16592295
TI  - On some modified spherical models.
AB  - A one parameter family of models is considered which for zero value of the
      parameter alpha reduces to the familiar spherical model. The models for alpha > 0
      have a symmetry close to that of an Ising model. A heuristic discussion of phase
      transitions in these models leads to the conjecture that, if the spherical model
      (alpha = 0) exhibits a phase transition, then so do the models with alpha > 0,
      and that moreover the critical temperature remains the same, at least for
      sufficiently small alpha. The conjecture is checked on a mean field model.

PMID- 16592296
TI  - Source theory analysis of electron-positron annihilation experiments.
AB  - The phenomenological viewpoint already applied to deep inelastic scattering is
      extended to the discussion of electron-positron annihilation experiments. Some
      heuristic arguments lead to simple forms for the pion differential cross section
      that are in reasonable accord with the published experimental data in the energy
      interval 3-4.8 Gev.

PMID- 16592297
TI  - Transition dipole coupling in Amide I modes of betapolypeptides.
AB  - Our previous introduction of transition dipole coupling helped to explain the
      splittings in the Amide I modes of antiparallel chain pleated sheet polyglycine
      I. This mechanism has now been applied to the more likely rippled sheet structure
      of this polypeptide as well as to the pleated sheet structure of poly(L-alanine).
      A satisfactorily consistent explanation of the splittings in both polypeptides is
      obtained. Since a previously incorporated interaction constant has not been used
      in the present treatment, these results show that transition dipole coupling
      alone can provide the physical basis for understanding these splittings. It is
      therefore now possible to predict with confidence the hitherto unidentified
      v(pi,pi) frequency of the antiparallel chain pleated sheet as well as the
      characteristic frequencies of the parallel chain pleated sheet.

PMID- 16592298
TI  - Alleopathy and spatial competition among coral reef invertebrates.
AB  - Species of ectoprocts and solitary encrusting animals were subjected in aquaria
      to homogenates of 11 sympatric species of sponges and colonial ascidians. Five of
      the nine sponge species and one of the two ascidian species exhibited species
      specific allelochemical effects. Evidence suggests that alleochemical provide a
      wide-spread, specific, and complex mechanism for interference competition for
      space among natural populations of coral reef organisms. The existence of such
      species-specific mechanisms may provide a basis for maintenance of diversity in
      space-limited systems in the absence of high levels of predation and physical
      disturbance.

PMID- 16592299
TI  - Bounds for a joint distribution function with fixed sub-distribution functions:
      Application to competing risks.
AB  - This paper gives sharp bounds for the joint survival function G(t(1),
      t(2),...,t(r)) identical with P(X(1) > t(1), X(2) > t(2),...,X(r) > t(r)), and
      for the marginal survival functions S(j)(t) identical with P(X(j) > t), j =
      1,2,...,r, when the sub-survival functions S(j) (*)(t) identical with P(X(j) > t,
      X(j) = min(k=1,2),...,(r)X(k)) are fixed. Theorem 1 gives the bounds for r = 2,
      and Theorem 2 gives the bounds for general r. Theorem 3 applies the result to the
      competing risks problem, and presents empirical bounds based on the observations.
      Finally, an example illustrates the bounds.

PMID- 16592300
TI  - Localization of phytochrome in etioplasts and its regulation in vitro of
      gibberellin levels.
AB  - Etioplasts isolated from barley leaves and purified on a Sephadex G-50 (coarse)
      column were characterized by electron microscopy and nucleic acid analysis. The
      majority of etioplasts retained an intact outer envelope, and contamination by
      other fragments was extremely low. The level of gibberellin-like substances
      extractable from intact etioplast suspensions was enhanced within 5 min of the
      termination of a saturating red irradiation, and the response was far-red
      reversible. Ultra-sonication caused a 3-fold increase in extractable activity
      both in dark control suspension and suspensions treated with red light. It is
      concluded that phytochrome, as a function of its interconversions, probably
      causes the transport of gibberellin from inside the etioplast into the
      surrounding medium. This leads to increased production of active gibberellins,
      possibly by release of feedback control of late steps of the biosynthetic
      pathway. Dual wavelength difference spectrophotometry has demonstrated the
      presence of a proportion of total cellular phytochrome within the etioplast.

PMID- 16592301
TI  - Species-area relation for birds of the Solomon Archipelago.
AB  - Accurate values of number of breeding bird species have been obtained for 50
      islands of the Solomon Archipelago. From information about species altitudinal
      distributions on each island, the values are apportioned into number of montane
      species (S(mt)) and of species present at sea-level (S(low)). S(low) increases
      linearly with the logarithm of island area A over a million-fold range of areas
      (correlation coefficient 0.99) and with a comparatively low slope, while the log
      S-log A relation is markedly curved. With increasing isolation of an archipelago,
      the species-area relation decreases in slope and may shift in form from a power
      function to an exponential. Comparison of Pacific archipelagoes at different
      distances from the colonization source of New Guinea shows that the decrease in
      slope is due to increasing intra-archipelago immigration rates, arising from
      overrepresentation of the most vagile inter-archipelago immigrants in more
      distant archipelagoes. When colonists are sorted into sets correlated with their
      dispersal abilities, the slope of the species-area relation for the most vagile
      set is close to zero, but for the least vagile set is close to the value
      predicted by Preston for "isolated universes."

PMID- 16592302
TI  - Bedload measurements, East Fork River, Wyoming.
AB  - A bedload trap in the riverbed provided direct quantitative measurement of debris
      transport rate in the East Fork River, Wyoming, a basin of 466 km(2) drainage
      area. Traction load moves only during the spring snow melt season. Data collected
      in three spring runoff seasons during which a peak flow of 45 m(3)/s occurred
      showed that transport rate is correlated with power expenditure of the flowing
      water and at high flows becomes directly proportional to power as suggested by
      Bagnold.

PMID- 16592303
TI  - On computing the Discrete Fourier Transform.
AB  - New algorithms for computing the Discrete Fourier Transform of n points are
      described. For n in the range of a few tens to a few thousands these algorithms
      use substantially fewer multiplications than the best algorithm previously known,
      and about the same number of additions.

PMID- 16592304
TI  - Relativized problems with abelian phase group in topological dynamics.
AB  - Let (X, T) be the equicontinuous minimal transformation group with X =
      pi(infinity)Z(2), the Cantor group, and S = [unk](infinity)Z(2) endowed with the
      discrete topology acting on X by right multiplication. For any countable group T
      we construct a function F:X x S --> T such that if (Y, T) is a minimal
      transformation group, then (X x Y, S) is a minimal transformation group with the
      action defined by (x, y)s = [xs, yF(x, s)]. If (W, T) is a minimal transformation
      group and varphi:(Y, T) --> (W, T) is a homomorphism, then identity x varphi:(X x
      Y, S) --> (X x W, S) is a homomorphism and has many of the same properties that
      varphi has. For this reason, one may assume that the phase group is abelian (or
      S) without loss of generality for many relativized problems in topological
      dynamics.

PMID- 16592305
TI  - On the structure of complete simply-connected Kahler manifolds with nonpositive
      curvature.
AB  - We prove that a complete simply-connected Kahler manifold with nonpositive
      sectional curvature is biholomorphic to the complex Euclidean space if the
      curvature is suitably small at infinity.

PMID- 16592306
TI  - Proton relaxation and charge accumulation during oxygen evolution in
      photosynthesis.
AB  - The water proton spin-spin (transverse) relaxation rate of chloroplast
      suspensions has been measured after each of a series of 2.4 musec light flashes.
      The sequence of relaxation rates shows a damped oscillatory pattern with a period
      of four and peaks after the 3rd, 7th, 11th, and 15th flashes. This result
      indicates that water proton relaxation can be used to monitor the charge
      accumulating states as postulated by Kok and coworkers for the oxygen-evolving
      mechanism in green plants [(1970) Photochem. Photobiol. 11, 457-475]. Other
      experiments [Wydrzynski et al. (1975) Biochim. Biophys. Acta 408, 349-354] have
      shown that the proton relaxation rate is strongly influenced by membrane-bound
      manganese in various oxidation states, suggesting that manganese participates in
      the charge accumulation process during oxygen evolution.

PMID- 16592307
TI  - Hydrogen evolution: A major factor affecting the efficiency of nitrogen fixation
      in nodulated symbionts.
AB  - Nitrogenase-dependent hydrogen evolution from detached legume nodules and from
      reaction mixtures containing cell-free nitrogenase has been well established, but
      the overall effect of hydrogen evolution on the efficiency of nitrogen fixation
      in vivo has not been critically assessed. This paper describes a survey which
      revealed that hydrogen evolution is a general phenomenon associated with nitrogen
      fixation by many nodulated nitrogen-fixing symbionts. An evaluation of the
      magnitude of energy loss in terms of the efficiency of electron transfer to
      nitrogen, via nitrogenase, in excised nodules suggested that hydrogen production
      may severely reduce nitrogen fixation in many legumes where photosynthate supply
      is a factor limiting fixation. With most symbionts, including soybeans, only 40
      60% of the electron flow to nitrogenase was transferred to nitrogen. The
      remainder was lost through hydrogen evolution. In situ measurements of hydrogen
      evolution and acetylene reduction by nodulated soybeans confirmed the results
      obtained with excised nodules. In an atmosphere of air, a major portion of the
      total electron flux available for the reduction of atmospheric nitrogen by either
      excised nodules or intact nodulated plants was utilized in the production of
      hydrogen gas. Some non-leguminous symbionts, such as Alnus rubra, and a few
      legumes (i.e., Vigna sinensis) apparently have evolved mechanisms of minimizing
      net hydrogen production, thus increasing their efficiency of electron transfer to
      nitrogen. Our results indicate that the extent of hydrogen evolution during
      nitrogen reduction is a major factor affecting the efficiency of nitrogen
      fixation by many agronomically important legumes.

PMID- 16592308
TI  - Ploy and counterploy in predator-prey interactions: Orb-weaving spiders versus
      bombardier beetles.
AB  - Bombardier beetles (Brachinus spp.) offered to orb-weaving spiders are either
      captured or lost, depending on the attack strategy of the spider. Nephila
      clavipes grasps a beetle directly and attempts to bite it outright, but is
      repelled by the beetle's defensive spray. As the spider recovers from the spray,
      the beetle makes its escape from the web. Argiope first imprisons the beetle by
      wrapping it delicately in silk, without causing it to spray. When the spider then
      proceeds to bite, the wrapping protects it against the full effects of the spray.
      The wrapping strategy may be generally effective against chemically protected
      insects, and it is suggested that this may be one of its principal adaptive
      justifications.

PMID- 16592309
TI  - Time-dependent response of soft polymers in moderately large deformations.
AB  - We present a theory that successfully describes the time-dependent mechanical
      behavior of soft incompressible isotropic polymers in moderately large
      deformations. The theory is based on the introduction of a generalized measure of
      strain into the Boltzmann superposition integral.

PMID- 16592310
TI  - Equilibrium and stability code for a diffuse plasma.
AB  - A computer code to investigate the equilibrium and stability of a diffuse plasma
      in three dimensions is described that generalizes earlier work on a sharp free
      boundary model. Toroidal equilibria of a plasma are determined by considering
      paths of steepest descent associated with a new version of the variational
      principle of magnetohydrodynamics that involves mapping a fixed coordinate domain
      onto the plasma. A discrete approximation of the potential energy is written down
      following the finite element method, and the resulting expression is minimized
      with respect to the values of the mapping at points of a rectangular grid. If a
      relative minimum of the discrete analogue of the energy is attained, the
      corresponding equilibrium is considered to be stable.

PMID- 16592312
TI  - The inverse problem for convex bodies.
AB  - A completely rigorous study of the high frequency asymptotics for the scattering
      matrix in the exterior of convex bodies is developed. These results are then
      applied to a variety of inverse problems for convex bodies.

PMID- 16592311
TI  - Viscosity of liquid metals: An interpretation.
AB  - The fluidity of liquid metals, like that of simple nonmetallic liquids, is a
      linear function of the ratio of unoccupied volume to intrinsic volume over long
      ranges as expressed by the equation varphi = B[(V/V(0)) - 1]. Values of V(0)
      obtained by extrapolating to varphi = 0 agree well with molal volumes of compact
      crystals at 20 degrees C calculated from densities.Values of the ratio
      varphi/[(V/V(0)) - 1] range from 27.0 for Na to 1.55 reciprocal centipoise for
      Ni. Viscosities at ratios of expansion V/V(0) = 1.10 vary linearly with squares
      of solubility parameters DeltaE(v)/V(0), where DeltaE(v) is molal energy of
      vaporization at the melting point. Viscosities at 10% expansion range from 0.037
      cP for Na to 5.38 cP for Co, with some divergence for metals with values of eta
      in the neighborhood of unity. The good agreement in the case of the transition
      metals Cu, Fe, Co, and Ni we attribute to distribution of vector momentum among
      quasi-chemical bonds between d-electrons and vacant orbitals.

PMID- 16592313
TI  - Unstable spiral modes in disk-shaped galaxies.
AB  - The mechanisms for the maintenance and the excitation of trailing spiral modes of
      density waves in diskshaped galaxies, as proposed by Lin in 1969 and by Mark
      recently, are substantiated by an analysis of the gas-dynamical model of the
      galaxy. The self-excitation of the unstable mode in caused by waves propagating
      outwards from the corotation circle, which carry away angular momentum of a sign
      opposite to that contained in the wave system inside that circle. Specifically, a
      simple dispersion relationship is given as a definite integral, which allows the
      immediate determination of the pattern frequency and the amplification rate, once
      the basic galactic model is known.

PMID- 16592314
TI  - Solar abundance of osmium.
AB  - The abundance parameter, log gfA, where g is the statistical weight of the lower
      level, f is the oscillator strength, and A is the abundance (by numbers of atoms
      with respect to hydrogen), has been derived for three lines of osmium by a method
      of spectrum synthesis. An apparent discordance of the derived abundance with that
      found from the carbonaceous chondrites is probably to be attributed primarily to
      errors in the f-values, and blending with unknown contributors.

PMID- 16592316
TI  - Lifting derivations from quotients of separable C-algebras.
AB  - If pi: A-->B is a surjective morphism between separable C(*)-algebras, then for
      each derivation delta of B there is a derivation [unk]delta of A such that
      pi([unk]delta(a)) for each a in A.

PMID- 16592315
TI  - Angles between orthogonal spd bond orbitals with maximum strength.
AB  - An equation is derived for values of bond angles for two equivalent best spd
      hybrid bond orbitals with given amounts of s, p, and d character, and is applied
      in the discussion of structures of transargononic compounds, including the xenon
      and halogen fluorides. Bond orbitals with a rather small amount of d character
      tend to lie at angles 90 degrees and 180 degrees , and those with a larger
      amount, at somewhat smaller angles.

PMID- 16592317
TI  - A maximal function associated to the curve (t, t).
AB  - THE AUTHORS PROVE THAT [FORMULA: see text] is bounded from L(P)(R(2)) to
      L(P)(R(2)) for 1 < p </= infinity.

PMID- 16592318
TI  - An extension of the concept of inertial frame and of Lorentz transformation.
AB  - It is shown how particular kinds of fractional-linear (or projective)
      transformations generalize the notion of inertial frame in that they ensure that
      free-particle motion goes over into free-particle motion. A ten-parameter group
      of such transformations is produced which generalize Lorentz transformations, and
      which involve besides c (velocity of light) a new fundamental length b; they
      encompass the ordinary Lorentz group in the limit that b becomes infinite. These
      extended Lorentz transformations are most simply understood as a type of rotation
      in the space of homogeneous coordinates, a rotation that unifies 3-space
      rotations, frame-shifts to moving frames, and space- as well as time
      translations. The structure of the invariant differential line element and of the
      wave operator that generalize those of special relativity are discussed, and
      implications for the possible revision of usual physical statements are pointed
      out.

PMID- 16592319
TI  - Birds on islands in the sky: Origin of the montane avifauna of Northern
      Melanesia.
AB  - Biogeographers have long been fascinated by the disjunct distributions of species
      stranded on mountaintops. This paper analyzes, for the montane bird populations
      of Northern Melanesian islands, how many such populations there are, why they are
      restricted to mountains, and how they dispersed to mountains. The number of
      populations increases with island elevation and with montane area, and decreases
      with lowland area, exemplifying the problem of continental species diversity.
      Most species with montane populations on some island(s) have sea-level
      populations on some other island(s). These altitudinal niche shifts can be
      variously related to interisland differences either in altitudinal distribution
      of area or else in competitive pressure in the lowlands or mountains. Restriction
      of Northern Melanesian bird populations to mountains is more often due to lowland
      competitors than to inability to survive under the physical conditions of the
      lowlands. Of four possible mechanisms for the origin of a montane population
      (referred to as jumping, land-bridge crossing, trickling, and push-pull shifts),
      only the first and last have been significant for Northern Melanesian birds.

PMID- 16592320
TI  - A van der Waals-type equation of state for fluids with associating molecules.
AB  - The basic assumptions of van der Waals theory are contained in two well-known
      concepts: excluded volume (repulsive forces) and a homogeneous, isotropic field
      potential (attractive forces). We have superimposed on these, one more well-known
      concept: the existence of dimers, trimers, etc., at chemical equilibrium. With
      reasonable simplifying assumptions, we obtain a closed-form equation of state,
      applicable to all fluid densities, and potentially useful for fluids containing
      strongly polar or hydrogen-bonded molecules. At all temperatures and at high
      densities, the equation of state suggests a phase transition where, because of
      extensive association, a new (solid-like) phase is in equilibrium with a "normal"
      fluid phase. The boundary between these phases has no critical point.

PMID- 16592321
TI  - New proposal for structure of special-pair chlorophyll.
AB  - A new model is proposed for the structure of the special pair of chlorophyll a
      molecules believed to correspond to the P700 species in green plants and algae.
      The proposed model, although admittedly speculative, is based upon exciton
      theoretical considerations and on in vitro infrared and visible absorption
      spectra of a 700 nm absorbing ethanol adduct of chlorophyll a. In the new model,
      two chlorophyll a molecules are held together by (a) two strong ring V keto
      C[unk]O[unk]H[unk]O (or keto C[unk]O[unk]H[unk]N, or keto C[unk]O[unk]H[unk]S)
      hydrogen bonds and by (b) pi-pi van der Waals stacking interactions between the
      two chlorophyll a macrocycles. Macrocycle stacking provides the intermolecular pi
      pi overlap necessary to promote the (experimentally observed) delocalization of
      the unpaired electron of the in vivo radical over two chlorophyll pi systems. The
      new model provides an explicit role for the participation of protein in the
      formation of the chlorophyll special pair. The in vitro system yields an electron
      spin resonance signal indistinguishable from that of oxidized P700 in Chlorella
      vulgaris.

PMID- 16592322
TI  - High dimensional cohomology of discrete groups.
AB  - For a large class of discrete groups Gamma, relations are established between the
      high dimensional cohomology of Gamma and the cohomology of the normalizers of the
      finite subgroups of Gamma. The results are stated in terms of a generalization of
      Tate cohomology recently constructed by F. T. Farrell. As an illustration of
      these results, it is shown that one can recover a cohomology calculation of Lee
      and Szczarba, which they used to calculate the odd torsion in K(3)(Z).

PMID- 16592323
TI  - On vector-valued asymptotic martingales.
AB  - In contrast to the vector-valued martingale which converges strongly almost
      everywhere if and only if the Banach space E has the Radon-Nikodym property, the
      vector-valued asymptotic martingale converges strongly almost everywhere if and
      only if E is of finite dimension.

PMID- 16592324
TI  - Conjugate points on a limiting extremal.
AB  - Theorem 1, together with the author's extensions of the Sturmian Comparison
      Theorems, will suffice to establish the basic Theorem 27.3, p. 211 of Global
      Variational Analysis: Weierstrass Integrals on a Riemannian Manifold.
      Mathematical Notes, Princeton University Press, Princeton, N.J., 1976. Here and
      in the preceding reference there is given a Weierstrass Integral on a compact,
      connected, Riemannian manifold M(n), conditioned as in the above reference. Let
      gamma be an arbitrary extremal of J joining a point P to a point Q, not equal P
      on M(n). An extremal zeta of J joining A to B is termed nondegenerate if A and B
      are not conjugate on zeta. The index of zeta is by definition the "count" of
      conjugate points of A on zeta definitely preceding B.THEOREM 1. When the extremal
      gamma is nondegenerate, extremals of J issuing from P with the same length as
      gamma and sufficiently near gamma in the sense of Frechet, are nondegenerate and
      have the same index as gamma.

PMID- 16592325
TI  - Kinetic theory and ergodic properties.
AB  - It is often assumed that the justification of kinetic theory lies in ergodic
      theory. From the properties of the collision operator, which plays a basic role
      in our kinetic description of dynamical systems, we show that this is not the
      case. We deduce that the asymptotic behavior of a class of states and observables
      is determined by the collisional invariants, independently of the ergodicity of
      the system. The relation between our conclusion and the stability concepts for
      classical Hamiltonian systems, introduced by Moser and others, is briefly
      indicated.

PMID- 16592326
TI  - Transcriptional origin of Euglena chloroplast tRNAs.
AB  - tRNA.DNA hybridization studies indicate that Euglena chloroplast tRNAs are
      transcriptional products of the chloroplast genome, which contains approximately
      26 tRNA cistrons. Hybridization with purified chloroplast tRNA(Phe) and tRNA(Asp)
      shows that the chloroplast genome contains one cistron for each of these two
      species. No hybridization of chloroplast tRNA with nuclear DNA was observed.
      tRNAs from Euglena cytoplasm, Escherichia coli, and Agmenellum quadraduplicatum
      do not compete with chloroplast tRNA for hybridization with chloroplast DNA.
      Evidence is presented that photoinduction of chloroplast tRNAs is at the level of
      transcription rather than maturation of tRNA precursor molecules.

PMID- 16592327
TI  - Rates of evolution in seed plants: Net increase in diversity of chromosome
      numbers and species numbers through time.
AB  - An approach was made to the problem of estimating rates of chromosomal evolution
      in plants. This was done by considering variability in chromosome number within
      genera whose ages are known approximately from fossil and biogeographic evidence.
      The relative increases in chromosome number diversity per lineage per unit time
      were as follows: herbaceous angiosperms, 100; woody angiosperms, 14; conifers, 2;
      and cycads, 0. Rates of increase in species diversity were estimated in an
      analogous way. These rates were strongly correlated with the karyotypic
      rates.These evolutionary rate differences between major groups of seed plants are
      largely explicable in terms of the breeding structures of populations. Herbs
      usually have small to moderate effective population sizes, and relatively high
      dispersability. By contrast, woody angiosperms and gymnosperms are usually
      obligate outbreeders with large effective population sizes and low
      dispersability. Thus the probability of fixing and dispersing new karyotypes or
      novel character ensembles is higher in herbs than in other seed plants.

PMID- 16592328
TI  - Species-distance relation for birds of the Solomon Archipelago, and the paradox
      of the great speciators.
AB  - For scattered remote islands and for likely forms of immigration and extinction
      curves, the equilibrium theory of island biogeography leads to the prediction
      [unk](2) log S/[unk]A[unk]D > 0, where S is the number of species on an island, A
      island area, and D island distance from the colonization source. This prediction
      is confirmed for birds of the Solomon Archipelago. Bird species can be classified
      into three types according to how distance affects their distributions: non-water
      crossers, which are stopped completely (usually for psychological reasons) by
      water gaps of even 1 mile; short-distance colonists, successful at colonizing
      close but not remote islands; and long-distance colonists, successful at
      colonizing remote as well as close islands. Almost all of the "great speciators",
      the species for whose inter-island geographic variation the Solomons are famous,
      prove to be short-distance colonists. Lack's interpretation of the decrease in S
      with D is shown to rest on incorrect assumptions.

PMID- 16592329
TI  - Maximal functions: Spherical means.
AB  - Let [unk](f)(x) denote the supremum of the averages of f taken over all (surfaces
      of) spheres centered at x. Then f --> [unk](f) is bounded on L(p)(R(n)), whenever
      p > n/(n - 1), and n >/= 3.

PMID- 16592330
TI  - Maximal functions: Homogeneous curves.
AB  - Let t --> gamma(t) be a homogeneous curve in R(n). For suitable f, define
      [unk](f)(x) = sup(h > 0)|(1/h) [unk](0) (h)f(x - gamma(t)) dt|. Then
      parallel[unk](f) parallel(p) </= A(p) parallelf parallel(p), 1 < p </= infinity.

PMID- 16592331
TI  - Classification of irreducible tempered representations of semisimple Lie groups.
AB  - For each connected real semisimple matrix group, one obtains a constructive list
      of the irreducible tempered unitary representations and their characters. These
      irreducible representations all turn out to be instances of a more general kind
      of representation, here called basic. The result completes Langland's
      classification of all irreducible admissible representations for such groups.
      Since not all basic representations are irreducible, a study is made of character
      identities relating different basic representations and of the commuting algebra
      for each basic representation.

PMID- 16592332
TI  - Redox titration of fluorescence yield of photosystem II.
AB  - The variable fluorescence yield of photosystem II is dependent on the redox state
      of the fluorescence quencher molecule or the primary electron acceptor of the
      system. We have carried out redox titrations of fluorescence yield of a
      photochemically active photosystem-II reaction-center particle and have measured
      the redox potential of the photosystem-II primary acceptor.During reductive
      titrations using dithionite as the reductant, only a single quenching transition
      was observed. For instance, at pH 7.0, the midpoint potential of the fluorescence
      transition is -325 mV, and those at a pH between 6.0 and 7.5 are consistent with
      a pH dependence of about 60 mV/pH unit. At a given pH, the midpoint potential of
      the transition closely corresponds to that of the most negative transition
      previously measured in unfractionated chloroplasts (both by chemical reductive
      titration). Oxidative titrations using ferricyanide as the oxidant yielded
      hysteresis in the titration curves.Similar changes in fluorescence yield were
      observed in redox titrations by electrochemical reduction or oxidation.
      Electrochemical reductive and oxidative titrations yielded reversible
      transitions, contrary to the hysteresis observed during chemical oxidative
      titration. From coulometric-titration data, we have estimated that most likely
      one electron is involved in the redox transition of the fluorescence-quencher or
      primary-electron-acceptor molecule of photosystem II. These findings are
      consistent with the current proposal that a membrane-bound plastoquinone
      functions as the primary acceptor of photosystem II.

PMID- 16592333
TI  - Chloroplast coupling factor 1: A species-specific receptor for tentoxin.
AB  - Tentoxin, a cyclic tetrapeptide, induces chlorosis in certain plant species. It
      inactivated photophosphorylation and coupling factor 1 (CF(1)) ATPase in lettuce,
      a sensitive species. This effect was due to binding of tentoxin with CF(1) at a
      single site (affinity constant 1.3 to 20 x 10(7) M(-1)). Neither AMP nor adenyl
      5'-yl imidodiphosphate appeared to bind to this site. In radish, an insensitive
      species, 20 times more tentoxin was required for 50% inhibition of
      photophosphorylation. In this species CF(1) ATPase was unaffected by tentoxin,
      and its CF(1) bound tentoxin only weakly (affinity constant less than 1 x 10(4)
      M(-1)). Sensitivity of photophosphorylation to tentoxin was correlated with
      chlorosis sensitivity in six other species examined.

PMID- 16592334
TI  - Influence of growth conditions upon the number of chloroplast DNA molecules in
      Euglena gracilis.
AB  - The number of chloroplast DNA molecules in Euglena gracilis cells was measured by
      determining the shift in the observed second-order rate constant for the
      reassociation of (125)I-labeled chloroplast DNA in the presence of unlabeled
      total cell DNA. Cells grown to stationary phase in the dark contained 217
      molecules of chloroplast DNA. Cells grown to stationary phase in the light in
      either heterotrophic or autotrophic medium contained 590 and 1014 chloroplast DNA
      molecules, respectively. The observed second-order rate constant for the
      reassociation of (125)I-labeled chloroplast DNA was not significantly altered in
      the presence of total cell DNA from a heat-bleached mutant, ZHB, which lacks
      chloroplast DNA. This evidence suggests that there is less than 0.3 of a
      chloroplast DNA molecule present in the nucleus of Euglena.

PMID- 16592335
TI  - Hybridization of potato spindle tuber viroid to cellular DNA of normal plants.
AB  - Molecular hybridization experiments of (125)I-labeled potato spindle tuber viroid
      (PSTV) with DNA from uninfected or PSTV-infected tomato plants showed that
      infrequent DNA sequences complementary to PSTV exist in both uninfected and
      infected cells. DNA titration experiments revealed that at least 60% of PSTV is
      represented by sequences in DNA of several normal solanaceous host species.
      Phylogenetically diverse plants contain sequences related to less of the PSTV.
      PSTV-infected tomato or Gynura aurantiaca plants did not possess new PSTV
      sequences at detectable levels. These results support the hypothesis that PSTV
      may have originated from genes in normal solanaceous plants.

PMID- 16592336
TI  - Medium-induced radiationless transitions and effect of solvent on radiationless
      transitions.
AB  - The purpose of this paper has been to investigate the effect of solvent on
      radiationless transitions. Two types of the solvent effect have been studied: one
      is the so-called medium-induced radiationless transition, i.e., the radiationless
      transition induced by the interaction between the solute and solvent, and the
      other is the effect of solvent on the radiationless transition through the change
      in energy gap induced by the solute-solvent interaction.

PMID- 16592337
TI  - Bernstein polynomials and Milnor algebras.
AB  - Let f be an analytic germ on C(n+1). Then there is an analytic linear partial
      differential operator P with polynomial dependence on s, and a polynomial b(s),
      such that Pf(s+1) = b(s)f(s). This paper contains a simple existence proof and
      geometric interpretation in the case when f has an isolated critical zero at the
      origin, and is contained in its Jacobian ideal of first partial derivatives.

PMID- 16592338
TI  - Maximal functions: Poisson integrals on symmetric spaces.
AB  - Let u be a harmonic function on a symmetric space which is the Poisson integral
      of a function f in L(p), 1 </= p </= infinity. Then u converges restrictedly and
      admissibly to f almost everywhere. This result is proved by obtaining an
      appropriate maximal theorem which takes into account the structure of the Poisson
      kernel.

PMID- 16592339
TI  - Extended x-ray-absorption fine structure-Auger process for surface structure
      analysis: Theoretical considerations of a proposed experiment.
AB  - A method for surface structure analysis is proposed. The proposed process
      combines x-ray photoabsorption and Auger electron emission. The extended x-ray
      absorption fine structure, occurring for photon energies above an atomic
      absorption edge, contains structural information of the microscopic environment
      due to the coupling of the photoelectron final state with the atomic initial
      state. Measurement of the variations in the intensity of particular Auger lines,
      as a function of the incident radiation energy, provides a surface sensitive
      measure of the photoabsorption cross section in the media. Theoretical
      considerations of the physical processes underlying the proposed experiment and
      its feasibility, and a discussion of background contributions are presented.

PMID- 16592340
TI  - Charge pair model of bioenergetics: Energy transfer.
AB  - The electron tunnelling distance between redox enzymes is estimated. The energy
      transfer mechanism between a pair of charges is described. The dielectric degrees
      of freedom are incorporated into the electron transfer rate formula.

PMID- 16592341
TI  - Experimental examination of the "energy upconversion" theory for green plant
      photosynthesis.
AB  - Spinach chloroplasts, dark adapted for periods of three days to three months,
      yield P700(+) formation (electron spin resonance signal 1) on the first as well
      as the following flashes in an actinic series of xenon light flashes of 10 mus
      duration. These data are in contradiction with the prediction of the "energy
      upconversion" theory [F. K. Fong (1975) Appl. Phys. 6, 151-156] that only the
      second flash would be effective.

PMID- 16592342
TI  - Cell recognition in plants: Determinants of the stigma surface and their pollen
      interactions.
AB  - The interaction between compatible pollen grains and the female stigma of
      Gladiolus gandavensis has been used as a model system for investigation of cell
      recognition in plants. The molecular architecture of the receptive stigma surface
      has been investigated, and determinants binding to both concanavalin A and beta
      glucosyl artificial carbohydrate antigen, as well as esterase activity, have been
      characterized, and conditions for their isolation have been established. The
      stigma surface, before and after modification, was found to bind (125)I-labeled
      proteins nonspecifically. Pollen tube penetration of the papillar cuticle is
      prevented when the receptor sites for concanavalin A are occupied. The
      concanavalin-A-binding determinants of the stigma surface have been fractionated
      to reveal several glycoproteins in the molecular weight range 43,000-93,000 and a
      group of glycolipids of molecular weight approximately 22,000. These results are
      interpreted in terms of two major recognition events regulating pollination.

PMID- 16592343
TI  - The unusual Favorskii-Nazarov reaction of dicyclopropyl ketone.
AB  - Dicyclopropyl ketone under Favorskii-Nazarov reaction conditions neither gave
      tetracyclopropylethylene glycol nor 1,1,4,4-tetracyclopropyl-1,4-butanediol by
      ether incorporation as expected. The hitherto unknown 1,1,5-tricyclopropyl-1
      hydroxypentan-5-one is obtained, presumably through the intermediacy of a dianion
      which nucleophilically attacks the neutral ketone through the cleavage of the
      cyclopropyl bond.

PMID- 16592344
TI  - Separation of hydrogenase-catalyzed hydrogen-evolution system from electron
      donating system by means of enzymic electric cell technique.
AB  - An enzymic electric cell was constructed in which the anode was composed of a
      zinc plate inserted in aqueous NH(4)Cl solution and the cathode was composed of
      an electrode made of a glassy carbon stick inserted in a reaction mixture
      containing cytochrome c(3) hydrogenase (H(2):ferricytochrome c(3) oxidoreductase,
      EC 1.12.2.1) and methylviologen under an atmosphere of N(2). When the circuit was
      closed, the electric cell formulated as [Formula: see text] was composed, and
      hydrogenase-catalyzed H(2)-evolution was observed in the cathode of the cell with
      concomitant flow of an electric current. Thus, the hydrogenase-catalyzed reaction
      and the electron-donating reaction proceeded at different parts of the cell. This
      enables us to protect the hydrogenase from the byproducts of the electron
      donating system, which might be hazardous to the enzyme.

PMID- 16592345
TI  - An equation of state describing hydrophobic interactions.
AB  - Several thermodynamic properties for the process of dissolution of pure
      hydrocarbons into water are found to be linearly related to the number of
      hydrogens on the hydrocarbon molecule. From the correlations found for the Gibbs
      energy change, enthalpy change, and heat capacity change, along with the use of
      an average minimum solubility temperature, an equation of state for the
      hydrophobic effect is derived. The entropy change upon dissolution per
      hydrocarbon hydrogen atom is close to -R ln 2. A model based upon a
      "tetrahedrally" localized water molecule with one corner defined by a carbon
      hydrogen group and the other three corners defined by water molecules is used to
      estimate the observed entropy and heat capacity changes.

PMID- 16592346
TI  - Magnetic circular dichroism of molecules in dense media: Spin-forbidden
      transitions of carbonyl molecules.
AB  - The purpose of this paper has been to calculate the magnetic rotational strength
      of the spin-forbidden (1)A(1) --> (3)A(2) transition of the carbonyl group. For
      this purpose, simple molecular orbitals have been used and only one-center
      integrals have been considered. The calculated results have been compared with
      the experimental measurements.

PMID- 16592347
TI  - Amine-catalyzed hydrolyses of cyclodextrin cinnamates.
AB  - Hydrolyses of beta-cyclodextrin cinnamate (betaCDC) and alpha-cyclodextrin
      cinnamate were catalyzed by amines such as 1,4-diazabicyclo(2.2.2)octane,
      triethylamine, quinuclidine, piperidine, diisobutylamine, and n-butylamine. The
      rate constant of hydrolyses of the betaCDC-amine complexes follows the order: 1,4
      diazabicyclo(2.2.2)octane > n-butylamine > quinuclidine > piperidine >
      triethylamine >> diisobutylamine. The ratio of the catalytic rate constant for
      the betaCDC/1,4-diazabicyclo(2.2.2)octane complex to the spontaneous rate
      constant for betaCDC is about 6-fold and is almost independent of pH below pH
      11.5; but, it then drastically increases with pH above pH 11.5, up to 57-fold at
      pH 13.6 which is much higher than previous attempts. The pH-rate constant profile
      and isotope effect with deuterium oxide solvent indicate that 1,4
      diazabicyclo(2.2.2)octane, included in betaCDC, assists the catalytic
      nucleophilic attack by hydroxide ion toward the carbonyl carbon of betaCDC.
      Acceleration of deacylation of acyl-cyclodextrins, by amines, has made the
      cyclodextrin-catalyzed hydrolysis of esters an even better model of hydrolytic
      enzyme reactions than those developed previously.

PMID- 16592348
TI  - Fossil microorganisms from the approximately 2800 to 2500 million-year-old
      Bulawayan stromatolite: Application of ultramicrochemical analyses.
AB  - Microfossils, probably representing members of Precambrian photosynthetic
      communities of bacteria and blue-green algae, have been found in the
      approximately 2800-2500 million-year-old Bulawayan stromatolites from Rhodesia.
      Several populations of coccoid and elongate microfossils have been observed in
      the dark, carbon-rich stromatolite laminae. Some of these elongate forms are
      morphologically similar to modern bacterial spores. These microfossils were
      studied in petrographic thin sections and identified by combined scanning
      electron microscopy-electron microprobe and by analyses of energy dispersive
      spectra of individual microfossils. The microfossils contain 1-20% organic
      carbon; some morphotypes contain traces of sulfur and one other, traces of
      phosphorus. The polymeric nature of the organic carbon was established by
      analyzing aggregates of microfossils at elevated temperatures in the solid inlet
      system of an organic mass spectrometer. The coccoid microfossils range in size
      from 1.2 to 4.3 mum, the elongate microfossils are from 2.4 to 9.8 mum. They are
      mineralized with dolomite, embedded in a calcite matrix, and are shown to be both
      indigenous and syngenous with the rock. Identical microfossils also containing
      organic carbon but mineralized with quartz have been observed in the
      stromatolites from Belingwe which are part of the Bulawayan Group from Rhodesia.
      Caution must be used in the interpretation of what these forms are because of
      their great age and relatively simple morphologies. However, based on morphology
      and chemical analyses, they represent fossilized bacteria, blue-green algae, or,
      most likely, both.

PMID- 16592349
TI  - Regulation of reserve protein metabolism in the cotyledons of mung bean
      seedlings.
AB  - Seedling growth in mung beans (Phaseolus aureus, Roxb.) is accompanied by the
      metabolism of the reserve proteins, and the appearance in the cotyledons of a
      proteolytic enzyme with endopeptidase activity. Enzyme activity increases 25-fold
      during the first 5 days of growth. Cotyledon extracts prepared from seeds imbibed
      for 24 hr with water do not react with rabbit endopeptidase antiserum, which
      suggests that the enzyme is not present in the seeds as a zymogen. Labeling
      experiments show that the enzyme is synthesized in the course of seedling growth.
      The endopeptidase is localized in the protein bodies, and the specific activity
      of the enzyme in these organelles increases 30-fold. Ultrastructural studies show
      that the rough endoplasmic reticulum proliferates and may give rise to vesicles
      which fuse with the protein bodies prior to reserve protein digestion. These
      vesicles could be the primary lysosomes which transport the enzyme from its site
      of synthesis to its site of action.

PMID- 16592350
TI  - Mechanism of nuclear DNA replication in radicles of germinating cotton.
AB  - The mechanism of nuclear DNA replication in radicles of germinating cotton
      (Gossypium barbadense) was investigated. Pulse-labeling with [(3)H]thymidine
      indicates that replication intermediates are of small molecular weight (4-10S)
      and behave as if single-stranded. Prolonged labeling indicates that intermediates
      are of discrete size, suggesting a mechanism of discontinuous replication.
      Electron microscopy of nuclear DNA demonstrates a complex architecture which may
      include "eye forms" and "forks" similar to those reported in prokaryotes and
      animal systems. The possible universality of DNA replication mechanisms is
      discussed.

PMID- 16592351
TI  - A relation between automorphic forms on GL(2) and GL(3).
AB  - Let rho(n) denote the standard n-dimensional representation of GL(n,C) and rho(n)
      (2) its symmetric square. For each automorphic cuspidal representation pi of
      GL(2,A) we introduce an Euler product L(s,pi,rho(2) (2)) of degree 3 which we
      prove is entire. We also prove that there exists an automorphic representation II
      of GL(3)-"the lift of pi"-with the property that L(s,II,rho(3)) = L(s,pi,rho(2)
      (2)). Our results confirm conjectures described in a more general context by R.
      P. Langlands [(1970) Lecture Notes in Mathematics, no. 170 (Springer-Verlag,
      Berlin-Heidelberg-New York)].

PMID- 16592352
TI  - Deep inelastic scattering of leptons.
AB  - The description of deep inelastic scattering as an extrapolation between
      resonance production and diffractive scattering is extended to give successful
      quantitative representations for the structure functions of unpolarized electron
      scattering on protons and neutrons, and of neutrino, antineutrino scattering on
      nucleons. The same ideas also supply a prediction for the polarization asymmetry
      in deep inelastic electron-proton scattering (paper no. 2, to be published).

PMID- 16592353
TI  - Interacting quantum fields and the chronometric principle.
AB  - A form of interaction in quantum field theory is described that is physically
      intrinsic rather than superimposed via a postulated nonlinearity on a
      hypothetical free field. It derives from the extension to general symmetries of
      the distinction basic for the chronometric cosmology between the physical
      (driving) and the observed energies, together with general precepts of quantum
      field theory applicable to nonunitary representations. The resulting interacting
      field is covariant, causal, involves real particle production, and is devoid of
      nontrivial ultraviolet divergences. Possible physical applications are discussed.

PMID- 16592354
TI  - Studies on the recovery of crown gall tumor cells.
AB  - Our previous studies have shown that, while a persistent but potentially
      reversible suppression of the tumorous state appears to be a characteristic
      feature of the vegetative phase of teratoma shoot growth in the crown gall
      disease of plants, a recovery from that state occurs during the reproductive
      phase. An analysis has now been made of the reproductive process in an attempt to
      define the precise stage at which recovery occurs. The results of this analysis
      have shown that diploid somatic cells of teratoma-derived flower parts such as
      those found in petals and filaments are inherently neoplastic. On the other hand,
      haploid cells of plants grown from anthers of the same flowers and diploid cells
      of F(1) generation plants grown from teratoma-derived seed have, by generally
      accepted criteria, recovered from the tumorous state. These findings have been
      interpreted to mean that the loss of neoplastic properties occurs in crown gall
      teratoma cells during meiosis rather than during fertilization or later stages of
      the reproductive process.An analysis of more than 2000 teratoma-derived tumor
      shoots has shown, moreover, that a recovery from the tumorous state may also
      occur, although apparently as a very rare event, during the vegetative phase of
      teratoma shoot growth.

PMID- 16592355
TI  - Relationship of gliadin protein components to chromosomes in hexaploid wheats
      (Triticum aestivum L.).
AB  - The synthesis of the A-gliadin protein fraction derived from the endosperm of the
      grain of hexaploid bread wheats (Triticum aestivum L.), which is toxic in celiac
      disease, was associated with the alpha arm of the 6A chromosome through use of
      the substitution lines of "Cheyenne" chromosomes in "Chinese Spring". The
      association was made through the use of ditelocentric stocks of Chinese Spring.
      The synthesis of many other gliadin components in the gel electrophoretic
      patterns of these two varieties could be associated with particular chromosomes
      as well. All genes detected were located in the chromosomes of homoeologous
      groups 1 and 6. It is possible to remove some of the proteins toxic to people
      with celiac disease from wheat (flour) by chromosome manipulation. If the toxic
      factor is not widely distributed among the storage protein components, it may be
      possible to produce a wheat that would be safe for celiac patients to eat.

PMID- 16592356
TI  - A theorem on homogeneous functions and extended Cobb-Douglas forms.
AB  - A form for homogeneous functions is presented which shows them to be a very
      simple extension of the wellknown Cobb-Douglas functions with similar properties
      in production (and distribution) economics. This form thus suggests new
      possibilities for interpreting a wide variety of empirical and theoretical
      results in economics; it also provides contact with developments in other fields,
      such as information theory and geometric programming.

PMID- 16592357
TI  - Unstable spiral modes in disk-shaped galaxies: Enhancement of growth rate.
AB  - An additional effect not considered in our earlier papers is found to enhance the
      rate of growth of spiral modes in disk-shaped galaxies. This enhanced growth
      appears to be attributable to the combined influence of differential rotation and
      tangential forces. For certain galaxy models, rapid temporal growths are possible
      (comparable to those found in numerical experiments), but in many real galaxies,
      these tendencies to extreme growth rates are probably reduced to lower levels by
      competing effects such as wave absorption at inner Lindblad resonance.

PMID- 16592358
TI  - Deep inelastic scattering of charged leptons.
AB  - The concept of a model based on the hypothesis of smooth extrapolation rather
      than explicit dynamical speculation is expounded. The existing body of successful
      applications is extended to the longitudinal cross section in deep inelastic
      scattering, and predictions are made for the asymmetry in scattering of polarized
      electrons on polarized protons.

PMID- 16592359
TI  - Conductivity and structure of bilinear organic addition compounds.
AB  - The relationship between crystal structures and metallic conductivities of linear
      organic materials such as tetrathiafulvalene-tetracyanoquinodimethane is
      explained in terms of strong lateral elastic interactions between chains. A
      microdomain model is presented in which at high temperatures there are, in
      general, two coexisting phases on each stacked molecular chain. The ordering of
      (in general, four) phases on two interacting chains leads to a variety of phase
      transitions at low temperatures. By examining temperature-dependent electrical
      conductivities and magnetic susceptibilities one can establish the character of
      each such transition.

PMID- 16592360
TI  - Intracellular site of synthesis and localization of leghemoglobin in root
      nodules.
AB  - A majority of the total protein synthesis in host cell cytoplasm is inhibited by
      cycloheximide. Because leghemoglobin represents a large proportion of total
      cellular protein in the nodule, this observation suggests that leghemoglobin may
      be translated on the 80S-type ribosomes. Analysis of the nascent peptides
      isolated from free and membrane-bound polysomes showed that free polysomes
      contain more immunoreactive material against antibodies to leghemoglobin as
      compared to that of membrane-bound polysomes. When free and membrane-bound
      polysomes were incubated in a wheat embryo cell-free protein-synthesizing system,
      a larger percentage of the released polypeptides from free polysomes was found to
      be immunoreactive. Similar results were obtained by translation in vitro of the
      poly(A)-containing mRNA isolated from free and membrane-bound polysomes. For
      immunocytochemical localization of leghemoglobin, the antibodies were conjugated
      with ferritin. Antibody conjugates were strictly localized in the host cell
      cytoplasm and adjacent to the outer surface of the membrane surrounding the
      bacteroids. Ferritin was not found on the inner surface of the membrane or within
      the membrane sac. These data suggest that leghemoglobin is synthesized
      preferentially on the free polysomes in the host cell cytoplasm, directed by a
      poly(A)-containing 9S mRNA that is most likely of plant origin, and that its
      location is restricted to the host cell cytoplasm.

PMID- 16592361
TI  - Efficiency of energy transfer from photosystem II to photosystem I in
      Porphyridium cruentum.
AB  - The yield of energy transfer from photosystem II to photosystem I in Porphyridium
      cruentum varies from a minimum value of about 0.50 when the photosystem II
      reaction centers are all open to a maximum value between 0.90 and 0.95 when the
      centers are all closed.

PMID- 16592362
TI  - Serinol as an activator of toxin production in attenuated cultures of
      Helminthosporium sacchari.
AB  - Successive transfer in synthetic medium of spores and mycelial fragments from
      original toxin-producing cultures of Helminthosporium sacchari results in
      attenuated cultures which do not produce the host-specific toxin
      helminthosporoside. When attenuated cultures are grown on material obtained from
      the water wash of sugarcane leaves susceptible to this fungus, the production of
      heminthosporoside resumes. Compounds that activate toxin production in the fungus
      are present on the leaf surface and presumably arise via plant metabolism. One
      activator was identified as a novel free amine, serinol (2-amino-1,3
      propanediol). It activates toxin production in attenuated cultures at 1 muM.
      Several experiments described in this report argue against the selection theory
      for the attenuation of cultures. The biological significance and some possible
      mechanisms for the activation of toxin biosynthesis are discussed.

PMID- 16592363
TI  - Phytochrome-mediated de novo synthesis of phenylalanine ammonia-lyase: An
      approach using pre-induced mustard seedlings.
AB  - The molecular mechanism of enzyme (phenylalanine ammonia-lyase; EC 4.3.1.5)
      formation mediated by phytochrome in mustard seedlings was investigated by
      labeling the enzyme with deuterium followed by high resolution CsCl density
      gradient analysis. A favorable relationship between induced rise of activity and
      turnover of this short-lived enzyme (half-life 3-4 hr) was achieved by labeling
      pre-irradiated seedlings. The time course of deuterium incorporation during the
      light-mediated rise in enzyme activity that can be derived independently from
      density shifts and bandwidth changes demonstrates a stimulation of synthesis and
      degradation by phytochrome. When synthesis is faster than degradation, enzyme
      accumulates.

PMID- 16592364
TI  - Calculation of immigration and extinction curves from the species-area-distance
      relation.
AB  - Quantitative models of the species-area-distance relation, based on equilibria
      between immigration and extinction rates, have been tested against data for birds
      on 52 Solomon islands. Biologically reasonable models account for 98% of the
      variance in species number. The data are adequate to permit determination of
      immigration and extinction curves and the values of seven associated parameters.
      The resulting curves are very concave. Extinction rates vary almost exactly as
      the reciprocal of area, but the effect of area on immigration rates is slight.
      Recognition of major differences among species in immigration and extinction
      rates and in dispersal distances proves essential to a successful model.

PMID- 16592365
TI  - Allende meteorite: Isotopically anomalous xenon is accompanied by normal osmium.
AB  - The (184)Os/(190)Os ratio of six Allende meteorite samples was determined by
      neutron activation analysis. Four chromite concentrates gave a ratio differing
      from the terrestrial ratio by only -0.1 +/- 0.4%, although they contained highly
      anomalous xenon enriched by up to 67% in (124)Xe and 93% in (136)Xe. In view of
      this result and the normal isotopic composition of carbon and oxygen in these
      fractions, it seems very unlikely that the xenon anomalies were produced in a
      supernova by the p and r processes. More probably, the xenon anomalies were
      established in the early solar system, by mass fractionation during trapping of
      noble gases in solids and by spontaneous fission of a superheavy element.Two
      other samples, containing osmium from the calcium,aluminum-rich inclusions, also
      gave an (184)Os/(190)Os ratio within -0.1 +/- 0.5% of the terrestrial value,
      although these inclusions show well-established anomalies in the light elements
      oxygen and magnesium, which appear to be due to pre-solar dust grains of
      distinctive nuclear history. Apparently the stellar source of the anomalous
      oxygen and magnesium did not synthesize heavier elements.

PMID- 16592366
TI  - Metal clusters in catalysis: Hydrocarbon reactions.
AB  - A set of metal carbonyl clusters, Ru(3)(CO)(12), Os(3)(CO)(12), and
      Ir(4)(CO)(12), has been evaluated as catalysts for a series of hydrocarbon
      reactions which comprise skeletal rearrangement, metathesis, dehydrogenation,
      hydrogenation, isomerization, and H-D exchange. None was especially effective as
      a hydrogenation catalyst even for olefins. Os(3)(CO)(12) was a catalyst for H-D
      exchange between C(6)H(6) and D(2) at 195 degrees but the ruthenium congener was
      inactive at temperatures below 175 degrees , a temperature where ruthenium metal
      formed at an appreciable rate. Deuterium incorporation in the benzene was a
      single-step process. Ir(4)(CO)(12) was an effective catalyst for the conversion
      of cyclohexadiene to cyclohexene and benzene. A similar reaction occurred with
      cyclohexene but the rate was extremely low at 160 degrees . The ruthenium and
      osmium clusters catalyzed the isomerization of linear hexenes, with the former
      the more active. Relative rates for the hexenes were 1 > 2 > 3. At high
      temperatures, the osmium and iridium clusters catalyzed skeletal reactions of 2
      hexene, as evidenced by the formation of pentenes, heptenes, heptanes, and small
      amounts of propane.

PMID- 16592367
TI  - Covalently linked chlorophyll a dimer: A biomimetic model of special pair
      chlorophyll.
AB  - The synthesis of a covalent dimer of chlorophyll a which possesses properties
      strikingly similar to those exhibited by P700 special pair chlorophyll in vivo is
      described. The covalent dimer is characterized by several spectroscopic
      techniques. Hydrogen bonding nucleophiles, such as water, primary alcohols, and
      primary thiols, are effective in generating a species from solutions of 10 muM
      covalent dimer in hydrophobic solvents which absorbs light near 700 nm. Formation
      of this in vitro special pair is a rapid, spontaneous process at room
      temperature. The range of nucleophiles which promote this process suggests that
      amino acid residues may function in a similar fashion to form P700 in chlorophyll
      protein complexes. The photochemical properties of this in vitro special pair
      mimic those of in vivo P700 species. The 697 nm absorption of the in vitro
      special pair undergoes photo-bleaching rapidly in the presence of iodine that
      results in the production of a cation radical which exhibits an electron spin
      resonance signal similar to that of oxidized P700 observed in Chlorella vulgaris.

PMID- 16592368
TI  - Metal-metal bond lengths in complexes of transition metals.
AB  - In complexes of the transition metals containing clusters of metal atoms the
      cobalt-cobalt bond lengths are almost always within 1 pm of the single-bond value
      246 pm given by the enneacovalent radius of cobalt, whereas most of the observed
      iron-iron bond lengths are significantly larger than the single-bond value 248
      pm, the mean being 264 pm, which corresponds to a half-bond. A simple discussion
      of the structures of these complexes based on spd hybrid orbitals, the
      electroneutrality principle, and the partial ionic character of bonds between
      unlike atoms leads to the conclusion that resonance between single bonds and no
      bonds would occur for iron and its congeners but not for cobalt and its
      congeners, explaining the difference in the bond lengths.

PMID- 16592369
TI  - On completeness of the Bergman metric and its subordinate metric.
AB  - It is proved that on any bounded domain in the complex Euclidean space C(n) the
      Bergman metric is always greater than or equal to the Caratheodory distance. This
      leads to a number of interesting consequences. Here two such consequences are
      given. (i) The Bergman metric is complete whenever the Caratheodory distance is
      complete on a bounded domain. (ii) The Weil-Petersson metric is not uniformly
      equivalent to the Bergman metric in the Teichmuller space T(g) of any Riemann
      surface of genus g >/= 2.

PMID- 16592370
TI  - Maximal functions associated to smooth curves.
AB  - Let t --> gamma(t), 0 </= t </= 1, be a smooth curve in IR(n). Define the maximal
      function [unk](f) by [unk](f)(x) = sup(0<h</=1) (1/h) (0) (h) f(x - gamma(t)) dt.
      We state conditions under which parallel[unk](f) parallel(p) </= A(p) parallelf
      parallel(p), for 1 < p </= infinity.

PMID- 16592371
TI  - A moment equation description of magnetic reversals in the earth.
AB  - Low order moments of the alpha dynamo equations in a geophysical regime are
      related to the dependent variables in a reversing disk dynamo. The link suggests
      that nonperiodic reversal is an intrinsic feature of the alpha dynamo equations
      provided the forcing is vigorous and the toroidal and poloidal magnetic fields
      are sufficiently out of phase. The nonuniformities in reversal frequency are then
      attributable to subcritical instability.

PMID- 16592372
TI  - Viscosity of dilute gases and vapors.
AB  - The well-known formula for calculating the viscosity of hard sphere gases, eta(o)
      = 2(mkT)(1/2)/3pi(3/2)sigma(2), where sigma(2) is molecular cross section, is
      altered to eta(o) = K(MT)(1/2)/V(t) (2/3), where V(t) is the molal volume of a
      liquid that has expanded sufficiently to permit mean free paths long enough to
      have significant fractions of the random thermal momenta of molecules in free
      flight and M is molal mass.This formulation places upon a single straight line
      points for all nonpolar molecules, mono- and polyatomic molecules alike, over
      long ranges of temperature.

PMID- 16592373
TI  - Endonuclease recognition sites mapped on Zea mays chloroplast DNA.
AB  - The closed-circular DNA molecules of 85 x 10(6) daltons from Zea mays
      chloroplasts were isolated, digested with the restriction endonucleases Sal I,
      Bam I, and EcoRI, and the resulting fragments sized by agarose gel
      electrophoresis. A map of maize chloroplast DNA showing the relative location of
      all the Sal I recognition sequences and many of the Bam I and EcoRI recognition
      sites was determined. A DNA sequence representing approximately 15% of the Zea
      mays chloroplast genome is repeated. The two copies of this sequence are in an
      inverted orientation with respect to one another and are separated by a
      nonhomologous sequence representing approximately 10% of the genome length. The
      inverted repeats contain the genes for chloroplast ribosomal RNAs.

PMID- 16592374
TI  - Demonstration of a transitory tight binding of ATP and of committed P(i) and ADP
      during ATP synthesis by chloroplasts.
AB  - Rapid mixing, quenching, and filtration experiments with chloroplast thylakoid
      membranes, with energization by acid-base transition, demonstrate that an ATP
      tightly bound to the isolated membranes is a transient intermediate in the
      catalytic sequence for ATP synthesis. The experiments also show that most of the
      P(i) and ADP bound at a catalytic site is committed to ATP formation without
      interchange with medium P(i) or ADP. Other results give evidence that upon
      energization, the tightly bound ADP that is detectable in isolated thylakoid
      membranes or coupling factor ATPase is rapidly released to the medium from a
      catalytic site. These findings support an alternating site model in which an
      energy-requiring conformational transition loosens ATP binding at one site and
      simultaneously promotes P(i) and ADP binding at the other site in a manner
      favoring ATP formation.

PMID- 16592375
TI  - Path of electrons in photosynthesis.
AB  - Electrons, from the oxidation of water, inside the grana disks (thylakoids) are
      transferred across the membrane to the outside, to the Calvin cycle or the Hill
      oxidant. The span in redox level may be 2.3 V. Part of the system II chlorophyll
      is on the inside of the membrane and part on the outside. An electron trap is
      embedded in the membrane. Alternately, an excited chlorophyll on the inside gives
      an electron to the trap, and an excited chlorophyll on the outside gives a hole
      to the trap. Two quanta move an electron from inside to outside. The charging of
      this condenser drives the redox levels on the inside positive and those on the
      outside negative. The final voltages depend upon the electron flow and a carotene
      diode. A voltage of 0.3 is involved. Delayed light is the exact reverse of the
      light reaction. System I makes ATP.

PMID- 16592376
TI  - Development of the photosynthetic unit in lettuce.
AB  - A comparative study of polypeptide composition and freeze-fracture morphology of
      chloroplast membranes isolated from different, but photosynthetically active,
      regions of a romaine lettuce shoot is presented. Chloroplasts prepared from outer
      dark-green leaves possess a fully developed light-harvesting chlorophyll-protein
      complex, have low chlorophyll a:b ratios and display fracture faces similar to
      those found in other higher plant chloroplast membranes; chloroplasts from leaves
      more to the interior of the shoot, have a much lower content of chlorophyll, show
      high chlorophyll a:b ratios, are depleted in components of the light-harvesting
      chlorophyll-protein complex, and exhibit extensive modifications of their
      fracture faces. We have also re-examined the freeze-fracture morphology of
      chloroplast membranes from a barley b-deficient mutant that lacks the light
      harvesting chlorophyll-protein complex. A tentative interpretation of our
      findings suggests correlating the assembly of the light-harvesting chlorophyll
      protein complex into the chloroplast membranes with the appearance of large
      freeze-fracture B face particles in the stacked interior-membrane region, and
      differentiation of typical fracture faces.

PMID- 16592377
TI  - Significant structure theory applied to phase separation.
AB  - The significant structure theory of liquids has been applied to the partially
      miscible system of the O(3)-O(2) mixture, which exhibits partial miscibility in
      the temperature range from -195.5 degrees C to -179.9 degrees C. The
      thermodynamic condition for phase separation is given by the following
      inequality: [Formula: see text] A partition function for the binary liquid
      mixture is developed using significant liquid structure theory. Here X(i) is the
      mole fraction of either of the two components. We obtain the coexistence curve of
      the O(3)-O(2) system by varying the mole fractions of the components to find the
      temperature at which the two liquids separate. The agreement between theory and
      experiment is satisfactory.

PMID- 16592379
TI  - Calcium control of actin-activated myosin adenosine triphosphatase from
      Dictyostelium discoideum.

PMID- 16592378
TI  - Convex programs having some linear constraints.
AB  - The problem of concern is the minimization of a convex function over a normed
      space (such as a Hilbert space) subject to the constraints that a number of other
      convex functions are not positive. As is well known, there is a dual maximization
      problem involving Lagrange multipliers. Some of the constraint functions are
      linear, and so the Uzawa, Stoer, and Witzgall form of the Slater constraint
      qualifications is appropriate. A short elementary proof is given that the infimum
      of the first problem is equal to the supremum of the second problem.

PMID- 16592380
TI  - A potassium ionophore (valinomycin) inhibits lymphocyte proliferation by its
      effects on the cell membrane.

PMID- 16592381
TI  - Stereochemistry of polymerization by DNA-dependent RNA-polymerase from
      Escherichia coli: An investigation with a diastereomeric ATP-analogue.

PMID- 16592382
TI  - Chlorophyll lasers: Stimulated light emission by chlorophylls and Mg-free
      chlorophyll derivatives.
AB  - Stimulated emission and lasing have been demonstrated for chlorophyll a,
      chlorophyll b, and bacteriochlorophyll a as well as for the Mg-free chlorophyll
      derivatives pheophytin a and methyl pheophorbide a. Population inversion was
      obtained by optically pumping with an N(2) laser. For the three chlorophylls,
      lasing was observed for only the (0,0) vibronic region of the S(1) --> S(0)
      fluorescence band. In contrast, lasing was observed for both the (0,0) and (0,1)
      vibronic regions of the S(1) --> S(0) fluorescence band of pheophytin a and
      methyl pheophorbide a. Differences between the lasing behavior of the
      chlorophylls and the Mg-free derivatives probably reflect differences in
      aggregation behavior. Laser pulses of duration shorter than the fluorescence
      lifetimes were generated. This result suggests that stimulated emission must be
      considered in the interpretation of fluorescence lifetime data for in vitro and
      in vivo chlorophyll-containing systems.

PMID- 16592383
TI  - A method of computational magnetohydrodynamics defining stable Scyllac
      equilibria.
AB  - A computer code has been developed for the numerical calculation of sharp
      boundary equilibria of a toroidal plasma with diffuse pressure profile. This
      generalizes earlier work that was done separately on the sharp boundary and
      diffuse models, and it allows for large amplitude distortions of the plasma in
      three-dimensional space. By running the code, equilibria that are stable to the
      so-called m = 1, k = 0 mode have been found for Scyllac, which is a high beta
      toroidal confinement device of very large aspect ratio.

PMID- 16592384
TI  - Electron affinity of the methyl radical: Structures of CH(3) and CH(3)-.
AB  - Ab initio self-consistent field and configuration interaction calculations are
      presented for the methyl radical and anion. The methyl radical is shown to be
      planar (D(3h)), while the anion is pyramidal (C(3v)). The methyl anion is
      unstable with respect to the limit of CH(3) plus an electron by 2-8 kcal/mole.
      Potential curves for the out-of-plane bending motions of both molecules are
      presented.

PMID- 16592385
TI  - On the equivalence between the boundedness of certain classes of maximal and
      multiplier operators in Fourier analysis.
AB  - The relationship between certain multipliers generalizing the Hilbert transform
      and maximal operators generalizing the Hardy-Littlewood maximal function is
      studied and some consequences of this relation are derived.

PMID- 16592386
TI  - MacMahon's conjecture on symmetric plane partitions.
AB  - In 1898, P. A. MacMahon conjectured that the generating function for symmetric
      plane partitions with at most s rows and each part at most j has an especially
      simple closed form. An outline of the proof of this conjecture is given here.

PMID- 16592387
TI  - Random walks and generalized master equations with internal degrees of freedom.
AB  - We present an extension of the continuous-time random walk formalism to include
      internal states and to establish the connection to generalized master equations
      with internal states. The theory allows us to calculate physical observables from
      which we can extract the characteristic parameters of the internal states of the
      system under study.

PMID- 16592388
TI  - Robust nonlinear data smoothers: Definitions and recommendations.
AB  - Nonlinear data smoothers provide a practical method of finding smooth traces for
      data confounded with possibly long-tailed or occasionally "spikey" noise. While
      they are natural tools for analyzing time-series data, they can be applied to any
      data set for which a sequencing order can be established. Their resistance to the
      effects of unsupported extreme observations and their ability to respond rapidly
      to well-supported patterns make them valuable as tools for finding patterns not
      constrained to specific parametric form and as versatile data-cleaning
      algorithms. This paper defines some robust nonlinear smoothers that have
      performed well in Monte-Carlo trials and makes brief recommendations based upon
      that study.

PMID- 16592389
TI  - Structure of ribulose-1,5-bisphosphate carboxylase-oxygenase: Form III crystals.
AB  - A new crystal form (III) of tobacco leaf ribulosebisphosphate carboxylase [3
      phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39] has been grown by
      dialysis procedures, and is suitable for structural studies at near atomic
      resolution. The crystals exhibit birefringence, grow as pseudo-regular rhombic
      dodecahedrons, and belong to the tetragonal space group P4(2)2(1)2 with a = b =
      149 A, c = 138 A, and V = 3.04 x 10(6) A(3). Each unit cell contains two
      molecules, with two large and two small subunits per asymmetric unit. At low
      resolution (>10 A) the crystal structure is body centered belonging to space
      group 1422 with one large/small pair in the asymmetric unit. Thus, at low
      resolution the molecular symmetry is D(4), the highest possible symmetry for an
      oligomer of stoichiometry large(8)small(8). Form III crystals may be identical to
      crystalline inclusions found in chloroplasts.

PMID- 16592390
TI  - Surface, catalytic, and magnetic properties of small iron particles: The effect
      of chemisorption of hydrogen on magnetic anisotropy.
AB  - The superparamagnetic behavior of very small particles of metallic iron (ca 1.5
      nm), with about half of their atoms at the surface, is changed reversibly by
      adsorption and desorption of hydrogen below the superparamagnetic transition
      temperature. The change after adsorption implies a lowering of the anisotropy
      energy barrier for the magnetic relaxation of iron and is ascribed to a change in
      crystalline shape. No such changes are observed for larger particles of iron (ca
      8 nm) with about 10% of their atoms at the surface.

PMID- 16592391
TI  - Explicit Plancherel theorem for ground state representation of the Heisenberg
      chain.
AB  - In its ground state representation, the infinite spin 1/2 Heisenberg chain
      provides a model for spin wave scattering that entails many features of the
      quantum mechanical N-body problem. Here, we give a complete eigenfunction
      expansion for the Hamiltonian of the chain in this representation, for all
      numbers of spin waves. Our results resolve the questions of completeness and
      orthogonality of the eigenfunctions given by Bethe for finite chains, in the
      infinite volume limit.

PMID- 16592392
TI  - Absorbing boundary conditions for numerical simulation of waves.
AB  - In practical calculations, it is often essential to introduce artificial
      boundaries to limit the area of computation. Here we develop a systematic method
      for obtaining a hierarchy of local boundary conditions at these artifical
      boundaries. These boundary conditions not only guarantee stable difference
      approximations, but also minimize the (unphysical) artificial reflections that
      occur at the boundaries.

PMID- 16592393
TI  - Outstanding problems and instrumental prospects for the coming decade (A Review).
AB  - After a review of the discovery of external galaxies and the early classification
      of these enormous aggregates of stars into visually recognizable types, a new
      classification scheme is suggested based on a measurable physical quantity, the
      luminosity of the spheroidal component. It is argued that the new one-parameter
      scheme may correlate well both with existing descriptive labels and with
      underlying physical reality.Two particular problems in extragalactic research are
      isolated as currently most fundamental. (i) A significant fraction of the energy
      emitted by active galaxies (approximately 1% of all galaxies) is emitted by very
      small central regions largely in parts of the spectrum (microwave, infrared,
      ultraviolet and x-ray wavelengths) that were previously inaccessible to
      observation. The physical processes by which regions with less, similar 10(-9)
      the volume of the luminous stellar parts of galaxies produce such enormous
      quantities of energy are currently the subject of much speculative debate. (ii)
      It appears that most of the mass of ordinary galaxies resides far from the
      central luminous region, with the volume containing most of this mass greater,
      similar 10(3) times the volume containing most of the light-emitting stars; the
      nature, amount, and extent of this mass are quite unknown.New instruments that
      will be operating in the next decade and that may be helpful in solving these two
      problems are briefly mentioned with particular emphasis on the advances expected
      in angular resolution at wavelengths for which picture-taking ability has
      historically been poor or nonexistent.

PMID- 16592394
TI  - Calabi's conjecture and some new results in algebraic geometry.
AB  - We announce a proof of Calabi's conjectures on the Ricci curvature of a compact
      Kahler manifold and then apply it to prove some new results in algebraic geometry
      and differential geometry. For example, we prove that the only Kahler structure
      on a complex projective space is the standard one.

PMID- 16592395
TI  - Extended Watson integrals for the cubic lattices.
AB  - The known exact expressions for extended Watson integrals relating to various
      cubic and modified cubic lattices are summarized. A new closed form expression
      for Watson's result on the simple cubic lattice is given in terms of gamma
      functions.

PMID- 16592396
TI  - Direct observations of atomic diffusion by scanning transmission electron
      microscopy.
AB  - The feasibility of using a high-resolution scanning transmission electron
      microscope to study the diffusion of heavy atoms on thin film substrates of low
      atomic number has been investigated. We have shown that it is possible to
      visualize the diffusion of individual uranium atoms adsorbed to thin carbon film
      substrates and that the observed motion of the atoms does not appear to be
      induced by the incident electron beam.

PMID- 16592397
TI  - Light collection and harvesting processes in bacterial photosynthesis
      investigated on a picosecond time scale.
AB  - Fluorescence lifetimes have been determined for four strains of Rhodopseudomonas
      sphaeroides. Chromatophore samples were excited with a single picosecond flash,
      and the fluorescence was detected with a streak camera. The decay times are 100
      psec in strains 2.4.1 and Ga, and 300 psec in the carotenoidless strain R-26.
      These times are related to the transfer of energy from the light-harvesting
      antenna pigment molecules to the photochemical reaction center. In strain PM-8
      dpl, which lacks reaction centers, the lifetime is 1.1 nsec. In addition, we have
      obtained curves relating the quantum yield of fluorescence to the photon density
      of the excitation pulse. These curves can be fit with a simple model that relates
      excitonic processes to properties of the photosynthetic unit and that
      qualitatively describes differences between the mutant strains.

PMID- 16592398
TI  - Quantum yields for oxygenic and anoxygenic photosynthesis in the cyanobacterium
      Oscillatoria limnetica.
AB  - A comparison of the quantum yield spectra of the oxygenic (H(2)O as the electron
      donor) with the anoxygenic (H(2)S as the electron donor) photosynthesis of the
      cyanobacterium, Oscillatoria limnetica reveals that anoxygenic photosynthesis is
      driven by photosystem I only. The highest quantum yields of the latter (maximum;
      0.059 CO(2) molecules/quantum of absorbed light) were obtained with wavelengths
      which preferentially excite photosystem I (<550, >650) in which chlorophyll a and
      carotenoids are the major pigments. The addition of 3-(3,4-dichlorophenyl)-1,1
      dimethylurea had no effect on anoxygenic photosynthesis, and no enhancement in
      quantum efficiency was observed by a superimposition of light preferentially
      exciting photosystem II.Oxygenic photosynthesis efficiently utilizes only a
      narrow range of the absorption spectrum (550-650 nm) where light is provided in
      excess to photosystem II via phycocyanin. The quantum yield (0.033 CO(2)
      molecules/quantum of absorbed light) is lower than the theoretical yield by a
      factor of 3, possibly due to inefficient light transfer from photosystem II to I.
      Thus, 3-fold enhancement of oxygenic photosynthesis by superimposition of
      photosystem I light, and low quantum yields for anoxygenic photosynthesis, were
      obtained in this region. These results are consonant with the suggestion that
      such a cyanobacterium represents an intermediate stage in phototrophic evolution.

PMID- 16592399
TI  - On the cyclonic mean circulation of large lakes.
AB  - In large lakes, during the heating season, the combination of surface wind drift
      and solar heating results in the horizontal transport of some of the absorbed
      heat into the coastal zone. Large-scale vertical movements associated with
      alternating upwellings and downwellings distribute the heat over a deeper water
      mass than at mid-lake. As a result, the mean shape of isotherm surfaces is
      "domed" and, correspondingly, the lake surface is slightly raised near shore and
      depressed over the center thermocline dome. The mean circulation in geostrophic
      equilibrium with this surface elevation field is a cyclonic gyre. In Lake
      Ontario, the amplitude of the mean surface velocity associated with this gyre is
      of the order of 3 cm sec(-1).

PMID- 16592400
TI  - Tubular presentations pi of subsets of manifolds.
AB  - In this note the Weierstrass integral J is taken as L, the Riemann integral of
      length. Here M(n), n > 1, is a compact, connected manifold of class C(infinity)
      with a positive definite Riemann structure. Presentations (phi, U(phi)) in M(n)
      and geodesics (with the aid of the Euler-Riemann equations) are defined in Morse,
      M. (1976) "Global variational analysis: Weierstrass integrals on a Riemannian
      Manifold," Mathematical Notes (Princeton University Press, Princeton, NJ).
      Christoffel terminology is not suitable for our purposes. Conjugate points on a
      geodesic need a definition that does not distinguish between simple and nonsimple
      geodesics. Tubular presentations pi of an open neighborhood of a geodesic lead to
      such a definition. These presentations are locally biunique and "compatible" with
      the earlier biunique presentations in M(n). We shall use a presentation pi in
      proving Theorem A below. Theorem A is essential in computing the Frechet numbers
      of product manifolds as we shall show in a later paper.

PMID- 16592401
TI  - On differentiation of integrals.
AB  - A technique is introduced to relate differentiation and covering properties of a
      basis. In particular, we find that the basis associated with a sparse set of
      directions differentiates integrals of functions locally in L(2).

PMID- 16592403
TI  - Nomenclature of phosphorus-containing compounds of biochemical importance
      (Recommendations 1976).

PMID- 16592402
TI  - Sufficient conditions for subellipticity on weakly pseudo-convex domains.
AB  - Herein is outlined a method for studying a priori estimates by using the theory
      of ideals of functions. With this method a criterion is obtained for subelliptic
      estimates for the delta-Neumann problem. In case the boundary is real analytic,
      the theory of ideals of real-analytic functions gives a geometric interpretation
      of the criterion. For forms of type (p,n - 1), in which n is the complex
      dimension of the domain, we obtain necessary and sufficient conditions for
      subellipticity on pseudo-convex domains. The study of propagation of
      singularities for delta leads one to conjecture that, for pseudo-convex domains,
      with real-analytic boundaries, subellipticity for (p,q)-forms holds if and only
      if there are no complex-analytic varieties of dimension greater than or equal to
      q in the boundary. The methods described here give results concerning the
      sufficiency of the condition in this conjecture.

PMID- 16592404
TI  - Promotion and inhibition of flower formation in a dayneutral plant in grafts with
      a short-day plant and a long-day plant.
AB  - Flower formation in the dayneutral tobacco (Nicotiana tabacum L.) cultivar
      "Trapezond" was accelerated by graft union with the short-day tobacco "Maryland
      Mammoth" when the grafts were kept on short days and by graft union with the long
      day plant N. silvestris L. when they were kept on long days. When Maryland
      Mammoth/Trapezond grafts were kept on long days, flower formation in Trapezond
      was not, or only slightly, delayed compared to Trapezond/Trapezond controls; but
      when N. silvestris/Trapezond grafts were kept on short days, flower formation in
      Trapezond was inhibited and its growth changed to dwarf-like habit. The former
      results indicate transmission of flower-promoting material(s) ("florigen") from
      photoperiodic plants maintained under flower-promoting daylength conditions to a
      dayneutral graft partner; the latter indicate the presence in the long-day plant
      N. silvestris under short-day conditions of potent flower-inhibiting and growth
      regulating material(s) that can also be transmitted to a day-neutral partner.
      Analogous flower-inhibitory materials seem not to be present, or to be present to
      a much lesser extent, in the short-day plant Maryland Mammoth under long-day
      conditions.

PMID- 16592405
TI  - General variational principles applicable to the hybrid element method.
AB  - Functional valued operators are used to formulate diffraction problems in a
      general abstract form. Variational principles for this formulation are developed.
      They are then applied to derive results on the linearized theory of free surface
      flows previously reported. Applications are also made to potential theory and
      elasticity.

PMID- 16592406
TI  - Single partition function for three phases.
AB  - The significant structures theory of liquids has been extended to take into
      account (i) translational degrees of freedom in the degeneracy term and (ii) the
      perturbation term which becomes important near the critical region. With these
      improvements, the calculated thermodynamic properties of argon agree very well
      with experimental results from the melting point through the critical point,
      along the coexistence curve as well as along the critical isochore and for the
      solid and the vapor.

PMID- 16592407
TI  - Covalence of atoms in the heavier transition metals.
AB  - The observed magnetic properties of the heavier transition metals permit them to
      have larger metallic valences than their iron-group congeners. With 0.72 metallic
      orbital, as found for the iron-group metals, the maximum metallic valence and
      minimum interatomic distance would occur for 8.28 transargononic electrons. The
      curves of observed interatomic distances for the close-packed metals of the
      second and third long periods have minima at this point, supporting the
      assignment of high valences to these metals. Values of the single-bond radii
      corresponding to these valences are calculated.

PMID- 16592408
TI  - Mathematical description of molecular structure: Molecular topology.
AB  - The concepts of the topology of finite point sets are applied to a mathematical
      description of molecular structure. The combinatorial properties of the "bond
      topology," which arises naturally from atomic adjacency relationships within a
      molecule, are investigated in detail. The collection of closed sets, the
      cotopology, is found to be related to bonding. Combinatorial weights of bonds
      over the cotopology are defined and explicit expressions for a general molecule
      are derived. The bond weights are found to parallel molecular orbital bond
      orders. It is concluded that much of the variation in pi bond orders is
      topological in origin.

PMID- 16592409
TI  - 1976 bedload measurements, East Fork River, Wyoming.
AB  - Quantitative measurements of bedload-transport rate in the East Fork River,
      Wyoming, show large spatial and temporal variabilities in traction load. The
      standard deviation for 1-min increments of the mean transport rate is commonly 50
      100% of the mean transport rate. The transport rates measured individually over
      eight equal-length increments of channel width indicate greater than 10-fold
      variations in transport rates from subwidth sections of minimum transport to
      subwidth sections of maximum transport.

PMID- 16592410
TI  - Classification of the irreducible representations of semisimple Lie groups.
AB  - We obtain a classification of the irreducible (nonunitary) representations of a
      connected semisimple Lie group G, in terms of their restriction to a maximal
      compact subgroup K of G. (A classification in terms of analytic properties of the
      representations has been given by R. P. Langlands [(1973), mimeographed notes,
      Institute for Advanced Study, Princeton, NJ] for linear groups.) We first define
      a norm on the representations of K: if mu in K, mu is a nonnegative real number.
      Then if pi in G, mu is called a lowest K-type of pi if mu is minimal among the K
      types occurring in pi. We announce a parameterization of the set of
      representations containing mu as a lowest K-type by the orbits of a finite group
      acting in a complex vector space (the dual of the vector part of a certain Cartan
      subgroup of G), and the result that mu necessarily occurs with multiplicity one
      in such representations.

PMID- 16592411
TI  - Analytic torsion and Reidemeister torsion.
AB  - We announce a proof of the conjecture of Ray and Singer that for a compact
      Riemannian manifold the analytic torsion and Reidemeister torsion are equal. The
      proof involves studying the heat equation for certain manifolds M, equipped with
      metrics g(u), 0 < u < 1 which degenerate in a prescribed way at the boundary
      deltaM, as u --> 0,1.

PMID- 16592412
TI  - A new class of counterexamples to the integrability problem.
AB  - For many years, it was believed that the solvability of the integrability problem
      for a transitive Lie pseudogroup depends only on the local solvability of linear
      differential operators arising from the abelian quotients in Guillemin's Jordan
      Holder decomposition for the transitive Lie algebra associated to the
      pseudogroup. We provide an example of a transitive pseudogroup for which the
      integrability problem is not solvable and whose corresponding Jordan-Holder
      sequence has only non-abelian quotients.

PMID- 16592413
TI  - Pseudo-monotone operators and nonlinear elliptic boundary value problems on
      unbounded domains.
AB  - A general boundary value problem of variational type is considered for a general
      quasi-linear elliptic partial differential operator of order 2m in generalized
      divergence form. Such problems are considered on an arbitrary domain in a
      Euclidean space without hypotheses of boundedness on the domain or smoothness on
      its boundary. Contrary to the prevailing doctrine in the literature, it is shown
      that the corresponding operator between Banach spaces is pseudo-monotone, and
      that a wide variety of existence results can be derived from this fact.

PMID- 16592414
TI  - Deformations of instantons.
AB  - A study is made of the self-dual Yang-Mills fields in Euclidean 4-space. For
      SU(2) gauge theory it is rigorously shown that the solutions depend on 8k - 3
      parameters, where k is the Pontrijagin index.

PMID- 16592415
TI  - Electromagnetism and gravitation.
AB  - Generation of electric fields in rapidly rotating insulators is discussed and
      calculated. An interesting effect is expected in TlCl. A possible appearance of
      magnetic fields near rapidly rotating gravitating bodies is proposed. The simple
      suggestion made here would lead to magnetic fields of negligible magnitude.

PMID- 16592416
TI  - Strong consistency of least-squares estimates in regression models.
AB  - A general theorem on the limiting behavior of certain weighted sums of i.i.d.
      random variables is obtained. This theorem is then applied to prove the strong
      consistency of least-squares estimates in linear and nonlinear regression models
      with i.i.d. errors under minimal assumptions on the design and weak moment
      conditions on the errors.

PMID- 16592417
TI  - Prediction and estimation for the compound Poisson distribution.
AB  - An empirical Bayes method is proposed for predicting the future performance of
      certain subgroups of a compound Poisson population.

PMID- 16592418
TI  - Source of oxygen in the CO(2) produced in the bioluminescent oxidation of firefly
      luciferin.
AB  - Incorporation of (18)O into the CO(2) produced in the bioluminescent oxidation of
      firefly luciferin was studied. In H(2) (16)O medium with (18)O(2) gas, the
      product CO(2) contained up to 75% C(16)O(18)O, showing that one O of the product
      CO(2) arose from the O(2) that oxidized luciferin. This result is consistent with
      a dioxetane mechanism. Analysis of the mass spectral data of the CO(2) obtained
      in high-enrichment H(2) (18)O medium with (16)O(2) gas indicated the presence of
      about 20% contaminating CO(2), which contributes approximately 70% of the total
      incorporated (18)O. Thus the values of incorporated (18)O in H(2) (18)O medium
      with (16)O(2) gas have no significance in the present context. Data obtained with
      luciferases of the American firefly Photinus and Japanese firefly Luciola were
      similar.

PMID- 16592419
TI  - Thermosensitive step associated with transfer of the Ti plasmid during
      conjugation: Possible relation to transformation in crown gall.
AB  - It is reported here that transfer by means of a conjugative process of an
      oncogenic plasmid from a virulent strain of Agrobacterium tumefaciens to a strain
      of that organism that had been cured of the plasmid is thermosensitive. Since the
      thermosensitive step found in the conjugative process appears similar in every
      respect to a thermosensitive step that is involved in the transformation of a
      normal cell to a tumor cell in the crown gall disease of plants, it is suggested
      that the observed results may reflect the existence of a thermosensitive step
      that is common to these two processes.

PMID- 16592420
TI  - Unique DNA associated with mitochondria in the "S"-type cytoplasm of male-sterile
      maize.
AB  - Mitochondrial DNAs were prepared from maize lines with normal cytoplasm and with
      the T, C, S, and EP sources of male-sterile cytoplasms. Agarose gel
      electrophoresis of these preparations revealed a main high-molecular-weight DNA
      band. In addition, the S cytoplasm was characterized by the presence of two
      faster migrating DNAs of molecular weight 3.42 to 3.48 x 10(6) and 4.01 to 4.10 x
      10(6). Electron microscopy showed these unique DNAs to be of different length,
      but their molecular configuration was not clearly established. It is possible
      that these unique DNAs represent physical evidence of an episomal system
      previously postulated to function in the S male-sterile cytoplasm.

PMID- 16592421
TI  - Replication of pea enation mosaic virus RNA in isolated pea nuclei.
AB  - Isolated nuclei from healthy pea plants were primed with pea enation mosaic virus
      (PEMV), southern bean mosaic virus (SBMV), radish mosaic virus (RdMV), tobacco
      mosaic virus (TMV), PEMV RNA, SBMV RNA, RdMV RNA, or TMV RNA. RNA replication
      occurred only with PEMV RNA and not with intact PEMV or any of the other viruses
      or RNAs, as judged by ensuing actinomycin D-insensitive polymerase activity.
      Molecular hybridization experiments showed that some of the product of the
      polymerase was PEMV-specific (-)RNA. The substrate and ionic requirements of this
      polymerase were the same as those for the RNA-dependent RNA polymerase present in
      nuclei isolated from PEMV-infected pea plants. No virus particles could be
      recovered from nuclei primed with PEMV RNA. These results are discussed in
      relation to the possible mechanism for in vivo infection of pea cells.

PMID- 16592422
TI  - Cell-to-cell stimulation of movement in nonmotile mutants of Myxococcus.
AB  - A large number of nonmotile mutants of the gliding bacterium Myxococcus xanthus
      have been isolated and partly characterized. About [unk] of these mutants are
      conditional mutants of a novel kind: mutant cells become transiently motile after
      contact with nonmutant cells or with cells of a different mutant type. These
      "stimulatable" mutants fall into five phenotypic classes (types B, C, D, E, and
      F). Most mutants are nonstimulatable (type A) and never become motile, but type A
      cells (and wild-type cells) can stimulate cells of any of the other five types.
      Stimulatable mutants of different types are capable of stimulating each other.
      For example, in a mixture of B and C cells, both become motile. Linkage analysis
      using a generalized transducing phage has shown that each of types B, C, D, E,
      and F corresponds to a single distinct genetic locus. Type A mutants, by
      contrast, belong to at least 17 different loci. Stimulation depends on close
      apposition of interacting cells, because stimulation does not occur when contact
      between cells is prevented. It is possible that the stimulatable mutants are
      defective in components of the gliding mechanism that can be exchanged between
      cells. Alternatively, they may be defective in a system of cell communication
      controlling the coordinated cell movements observed in Myxococcus.

PMID- 16592423
TI  - Reduction of pore area of the avian eggshell as an adaptation to altitude.
AB  - Standard measurements of water vapor conductance in units of mg of H(2)O . day(
      1) . torr(-1) (SI equivalent is mg of H(2)O . day(-1) . pascal(-1)) of fresh eggs
      of the red-winged blackbird (Agelaius phoeniceus) and the native chicken of India
      (Gallus gallus) collected at altitude are significantly less than those of eggs
      of the same species collected near sea level. This decrease is caused by a
      reduction of the total effective pore area of the eggshell at altitude. It
      appears to be proportional to the reduction in barometric pressure and the
      simultaneous increase in the diffusion coefficient of water vapor. Thus,
      reduction in pore area offsets increased diffusivity at altitude, and water vapor
      loss through the eggshell at any altitude remains the same as at sea level. The
      data suggest a structural adaptation of the shell to altered diffusivity of gases
      at altitude in order to prevent excessive water loss of eggs during natural
      incubation.

PMID- 16592424
TI  - Quantum statistical theory of optical phenomena.
AB  - The purpose of this paper is to develop a density matrix formulation for optical
      phenomena that can be applied to both steady and transient states and to both
      resonance and off-resonance regions. To demonstrate the application, this theory
      has been applied to the steady-state one-photon and two-photon processes. We have
      found that, in the resonance region, the conventional equation used is
      incomplete; other terms that are comparable in importance have been ignored.

PMID- 16592425
TI  - Detailed electronic description of triple bonds between transition metal atoms
      and verification by photoelectron spectroscopy.
AB  - Using the SCF-Xalpha-SW method the ground state electronic structures of
      (HO)(3)Mo identical withMo(OH)(3), (H(2)N)(3)Mo identical withMo(NH(2))(3), and
      (Me(2)N)(3)Mo identical withMo(NMe(2)) have been calculated. The results provide
      a detailed description of the metal-to-metal triple bonds present; some of the
      more important molecular orbitals are shown in detail as contour diagrams. The
      energy levels of all filled valence shell/molecular orbitals and the lower
      virtual orbitals are presented in diagrams. The pi(e(u)) and sigma(a(1g))
      orbitals which have large amounts of metal character can be identified as the
      orbitals primarily responsible for Mo-Mo bonding. Using the transition state
      technique to allow for relaxation effects, the photoelectron spectra (up to 12
      eV) have been calculated for Mo(2)(OH)(6) and Mo(2)(NH(2))(6) and found to
      compare very well, after applying a constant downshift to correct for inductive
      effects, with experimental spectra for Mo(2)[OCH(2)C(CH(3))(3)](6) and
      Mo(2)[N(CH(3))(2)](6). The experimental photoelectron spectra are reported.

PMID- 16592426
TI  - Blue copper proteins: Synthesis, spectra, and structures of CuN(3)(SR) and
      CuN(3)(SR) active site analogues.
AB  - The reaction of Cu(SR) or [Cu(SR)][ClO(4)] derivatives (SR = p
      nitrobenzenethiolate or O-ethylcysteinate) with potassium hydrotris(3,5-dimethyl
      1-pyrazolyl)borate produces redox pairs of the stoichiometry Cu(I)N(3)(SR) and
      Cu(II)N(3)(SR). These complexes are well-defined synthetic approximations to the
      proposed N(3)S binding sites of blue (type 1) copper electron transfer proteins.
      The compounds were investigated by a variety of chemical and spectral (optical,
      resonance Raman, and electron paramagnetic resonance) techniques; the complex
      K[Cu(hydrotris(3,5-dimethyl-1-pyrazolyl)borate)(p- NO(2)C(6)H(4)S]-2 acetone was
      also studied by single-crystal x-ray diffraction methods. The spectrochemical
      characteristics of the Cu(II)N(3)(SR) species are in large part similar to the
      native system and thus provide some perspective regarding the origin of the
      unique type 1 spectral parameters and electron transfer properties.

PMID- 16592427
TI  - Hyperbolic almost periodic solutions and toroidal limit sets.
AB  - We consider an almost periodic solution phi(t) of an autonomous differential
      equation x' = f(x). Let k denote the topological dimension of the hull H(phi). By
      considering the linearized equation x' = A(t)x alone [where A(t) is the Jacobian
      matrix of f evaluated along phi(t)], one can derive a sufficient condition in
      order that phi(t) be quasi-periodic and that the hull H(phi) be diffeomorphic to
      a k-dimensional torus T(k). The proof is based upon an extension of the center
      manifold theorem to nonautonomous nonperiodic differential systems.

PMID- 16592428
TI  - Complex submanifolds in real-analytic pseudoconvex hypersurfaces.
AB  - A theorem is given that guarantees the existence of nontrivial complex analytic
      submanifolds in real-analytic pseudoconvex boundaries near real-analytic
      submanifolds with holomorphic vectorfields on which the Levi form vanishes.
      Applications to the delta-Neumann problem and to the existence of Stein
      neighborhoods are discussed.

PMID- 16592429
TI  - An observation concerning electronically excited retinal.
AB  - The observation of Mathies and Stryer of highly polar excited electronic states
      of all-trans-retinal, its unprotonated Schiff base, a salt of the protonated
      Schiff base, and 11-cis-retinal leads us to propose a possible consequence of the
      existence of such species. The highly polar excited molecule may have sufficient
      potential to oxidize its surroundings, thus achieving a transfer of one electron.
      Experimental evidence is combined with crude model calculations to support the
      possible role of these excited states as electron transfer agents.

PMID- 16592430
TI  - Genetic instability in Drosophila melanogaster: De novo induction of putative
      insertion mutations.
AB  - The capacity of a so-called male recombination (MR) chromosome in Drosophila
      melanogaster to generate mutations at 14 X-chromosome loci specifying visible
      phenotypes was investigated. Appreciable increases in mutation were found at
      three loci y, sn, and ras. Tests of represnetative mutants generated at each
      locus establish all to be putative insertion mutants, as judged by their
      spontaneous mutability. These facts suggest that insertion mutation production
      may be a general function of MR chromosomes. The relationship of the MR
      chromosomes to established insertion elements (IS and Mu) is discussed.

PMID- 16592431
TI  - Pathways of genetic transfer from Tripsacum to Zea mays.
AB  - The cytogenetic interactions in maize x Tripsacum hybrid derivatives can be
      remarkably complex. The number of viable, somewhat female fertile chromosome
      combinations is astonishing. Fifty-four different combinations are listed in this
      paper, and others are certainly possible. In successive backcrosses to maize,
      chromosome numbers scale both up and down with ease, sometimes stabilizing for a
      few generations via apomixis, but in most cases finally generate balanced maize
      genomes and emerge as recovered maize. The maize, however, can produce strange
      and unusual phenotypes as a result of genetic transfers from Tripsacum. Highly
      tripsacoid maize lines with 2n = 20 chromosomes were recovered in pathways where
      the maize genome had first contaminated the Tripsacum genome in early backcross
      generations. In other pathways interaction of the two genomes is rare. Dominant
      resistances to six maize diseases were found in BC(8) populations.

PMID- 16592432
TI  - Gene regulation in Drosophila mulleri, D. arizonensis, and their hybrids: The
      nucleolar organizer.
AB  - Typically, Drosophila have nucleolar organizer regions (NORs) confined to the sex
      chromosomes. Salivary gland cells of hybrids between Drosophila mulleri females
      and D. arizonensis males exhibit features in nucleolar organizer regulation that
      differentiate the species on one hand, and which show an interplay between the X
      and the microchromosome on the other hand.In the hybrid females only the X
      chromosome from D. arizonensis appears to be attached to the nucleolus. In the
      hybrid males the X chromosome, from D. mulleri, also does not seem to contain a
      functional NOR. However, in hybrid males the microchromosome from D. arizonensis
      increases greatly in size and appears to be associated with the nucleolus. The
      increase in size of the microchromosome involves a 4-fold increase in DNA
      content. In D. arizonensis and in hybrid females the NOR of the microchromosome
      appears to be suppressed. In the absence of an arizonensis X chromosome, the NOR
      of the microchromosome typically is active, while the NOR on the mulleri X
      chromosome remains suppressed. Therefore, the ribosomal cistrons and
      interchromosomal regulator element appears to be duplicated on both the X
      chromosome and microchromosome of D. arizonensis, but with epistatic suppression
      of the microchromosomal NOR by the arizonensis X-linked NOR. Either arizonensis
      NOR, X linked or microchromosomal, suppresses the mulleri NOR.

PMID- 16592433
TI  - Occurrence of somatostatin-like immunoreactivity in some peripheral sympathetic
      noradrenergic neurons.
AB  - By means of the indirect immunofluorescence technique of Coons and collaborators,
      somatostatin-like immunoreactivity has been demonstrated in principal ganglion
      cells of some sympathetic ganglia. The noradrenergic nature of these cells was
      established by "staining" of the same or consecutive sections with antiserum to
      dopamine beta-hydroxylase [dopamine beta-monooxygenase; 3,4
      dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating),
      EC 1.14.17.1], the enzyme converting dopamine to noradrenaline (norepinephrine).
      In guinea pigs the somatostatin immunoreactive material was found in almost two
      thirds of all principal ganglion cells of the coeliac-superior mesenteric
      ganglion complex (anterior inferior part) and of the inferior mesenteric
      ganglion, but only in a few cells of the superior cervical ganglion. It appeared
      to be localized close to the Golgi complex. The present findings may represent a
      concomitant storage of a biogenic amine and a small peptide in a neuron. Because
      both noradrenaline and somatostatin may fulfill a role as a neurotransmitter or
      modulator, the sympathetic neurons described in this study may represent an
      example of mammalian nerve cells not conforming to Dale's hypothesis, i.e., the
      one neuronone transmitter concept.

PMID- 16592434
TI  - A general treatment of relaxation phenomena.
AB  - The singular perturbation method has been applied to solve the quantum mechanical
      Liouville equation for the relaxation phenomenon of the system in thermal contact
      with a heat bath. The master equation derived gives the proper expressions for
      both diagonal and off-diagonal elements of the density matrix and is capable of
      describing the time-dependent behavior of the system in the time range comparable
      with the reciprocal of the damping constants and the time range t --> infinity
      compared with the reciprocal of the damping constants.

PMID- 16592435
TI  - An observation on the structure of production sets with indivisibilities.
AB  - A subset of the constraints of an integer programming problem is said to be
      binding if, when the remaining constraints are eliminated, the smaller problem
      has the same optimal solution as the original problem. It is shown that an
      integer programming problem with n variables has a set of binding constraints of
      cardinality less than or equal to 2(n)-1. The bound is sharp.

PMID- 16592436
TI  - n-Type Si-based photoelectrochemical cell: New liquid junction photocell using a
      nonaqueous ferricenium/ferrocene electrolyte.
AB  - n-Type Si has been shown to serve as a stable photoanode in a cell for the
      conversion of light to electricity. The other components of the cell are a Pt
      cathode and an electrolyte consisting of an ethanol solution of [n-Bu(4)N]ClO(4)
      with a redox couple of ferricenium/ferrocene. Data from a two-compartment cell
      show that ferrocene is oxidized to ferricenium with 100 +/- 2% current efficiency
      at the Si photoanode. Furthermore, prolonged irradiation of the Si in a one
      compartment cell yields constant photocurrent and output characteristics. The
      maximum open-circuit photopotential is approximately 700 mV, and the short
      circuit quantum yield for electron flow at low light intensity exceeds 0.5.
      Conversion of monochromatic 632.8-nm light to electricity with approximately 2%
      power efficiency at an output voltage of approximately 200 mV has been sustained.
      These results represent a stable n-type Si-based photoelectrochemical cell.

PMID- 16592437
TI  - Electrophilic mercuration and thallation of benzene and substituted benzenes in
      trifluoroacetic acid solution.
AB  - The mercuration and thallation of benzene and substituted benzenes was studied
      with mercuric and thallic trifluoroacetate, respectively, in trifluoroacetic
      acid. With the shortest reaction time (1 sec) at 0 degrees , the relative rate of
      mercuration of toluene compared to that of benzene was 17.5, with the isomer
      distribution in toluene of: ortho, 17.4%; meta, 5.9%; and para, 76.7%. The isomer
      distribution in toluene varied with the reaction time, significantly more at 25
      degrees than at 0 degrees . The competitive thallation of benzene and toluene
      with thallic trifluoroacetate in trifluoroacetic acid at 15 degrees showed the
      relative rate, toluene/benzene, to be 33, with the isomer distribution in toluene
      of: ortho, 9.5%; meta, 5.5%; and para, 85.0%. With increasingly higher reaction
      temperatures in both mercuration and thallation reactions of aromatics,
      isomerization (both intramolecular and intermolecular) within the relevant ortho-
      and para-metallated intermediate ions and/or of the isomers becomes more
      important. Competitive rates and isomer distributions of mercuration and
      thallation of benzene and substituted benzenes were also determined. The
      predominant para substitution in both mercuration and thallation of
      methylbenzenes reflects, besides some steric factors, the strong stabilizing
      effect of para methyl groups on the arenium ion intermediates. Under
      predominantly kinetically controlled conditions, no anomalous increase in the
      amount of meta substitution was observed.

PMID- 16592438
TI  - Picosecond dynamics of iron proteins.
AB  - The excitation of hemoproteins containing either Fe(2+) or Fe(3+) with a
      picosecond light pulse resulted in the bleaching and recovery of the iron
      absorbance bands within 6 psec. A new absorbance band also was observed whose
      formation and decay rate of less than 6 psec suggests that it is probably due to
      S(1)-->S(n) absorbance. The Soret band relaxation time is deduced to be
      approximately 0.5 psec whereas the free base hemoprotein does not show any of the
      above fast-decay characteristics. Therefore, there is a strong influence of the
      metal on the energy dissipation process.

PMID- 16592439
TI  - Use of solvent cavity area and number of packed solvent molecules around a solute
      in regard to hydrocarbon solubilities and hydrophobic interactions.
AB  - Two currently used methods of calculating the area of contact between a solute
      molecule and the solvent are examined and some important differences are pointed
      out. Some pitfalls and uncertainties in the application of the concept of
      molecular surface area to the quantitative estimation of unitary free energies of
      solution are discussed.

PMID- 16592440
TI  - Resonance coherent anti-Stokes Raman scattering spectra of fluorescent biological
      chromophores: Vibrational evidence for hydrogen bonding of flavin to glucose
      oxidase and for rapid solvent exchange.
AB  - Coherent anti-Stokes Raman scattering (CARS) spectra are reported for flavin
      adenine dinucleotide (FAD) and glucose oxidase (beta-D-glucose:oxygen 1
      oxidoreductase; EC 1.1.3.4), in resonance with the 450 nm flavin absorption band.
      Several isoalloxazine ring modes were observed (1635, 1584, 1507, 1416, and 1359
      cm(-1)). A 12 cm(-1) increase in one component of the 1359 cm(-1) band upon
      binding to glucose oxidase was attributed to hydrogen bonding of the N3 proton to
      a protein acceptor. This interpretation is consistent with deuteration results.
      Smaller decreases (5-7 cm(-1)) on binding were observed for the 1635 and 1416 cm(
      1) modes (and also a 1297 cm(-1) mode of deuterated FAD) and were attributed to
      environmental effects. Deuteration of bound FAD was observed within 5 min of
      mixing glucose oxidase with D(2)O, demonstrating ready access to solvent.
      Lorentzian CARS peaks were observed with omega(as) at the peak of the 450 nm
      absorption band, a condition which corresponds to maximum resonance enhancement
      if the peak corresponds to the envelope of 0-1 vibronic transitions. If omega(1)
      was tuned to the peak, then dispersion lineshapes were observed, reflecting a
      loss of Raman enhancement relative to the electronic background.

PMID- 16592441
TI  - Restrictions on the coefficients of hyperbolic systems of partial differential
      equations.
AB  - THE PAPER DEALS WITH HYPERBOLIC HOMOGENEOUS SYSTEMS [FORMULA: see text] of
      partial differential equations with constant coefficients for an N-vector
      u(t,x(1),...,x(n)). Here, P is a matrix form of order N and degree m. In the
      scalar case (N = 1), every hyperbolic P is limit of strictly hyperbolic ones.
      This does not hold for systems as is shown here for the special case N = n = 3, m
      = 2. Assuming P(1,0,...,0) to be the unit matrix, we represent P by a point in
      R(81). The hyperbolic P form a closed set H in R(81), the strictly hyperbolic
      ones an open subset H(s) of H. An example is given for a P in H which is not in
      the closure of H(s). Moreover, it is shown that near that P the set H coincides
      with an algebraic manifold of codimension 4.

PMID- 16592442
TI  - Microscopic theory of irreversible processes.
AB  - The microscopic theory of irreversible processes that we developed is summarized
      and illustrated, using as a simple example the Friedrichs model. Our approach
      combines the Poincare's point of view (dynamical interpretation of
      irreversibility) with the Gibbs-Einstein ensemble point of view. It essentially
      consists in a nonunitary transformation theory based on the symmetry properties
      of the Liouville equation and dealing with continuous spectrum. The second law
      acquires a microscopic content in terms of a Liapounov function which is a
      quadratic functional of the density operator. In our new representation of
      dynamics, which is defined for a restricted set of observables and states, this
      functional takes a universal form. We obtain, in this way, a semi-group
      description, the generator of which contains a part directly related to the
      microscopic entropy production. The Friedrichs model gives us a simple field
      theoretical example for which the entropy production can be evaluated. The
      thermodynamical meaning of life-times is explicitly displayed. The transition
      from pure states to mixtures, as well as the occurrence of long tails in
      thermodynamic systems, are also briefly discussed.

PMID- 16592443
TI  - Gravitational interaction of hadrons: Band-spinor representations of GL(n,R).
AB  - We demonstrate the existence of double-valued linear (infinite) spinorial
      representations of the group of general coordinate transformations. We discuss
      the topology of the group of general coordinate transformations and its subgroups
      GA(nR), GL(n,R), SL(nr) for n = 2,3,4, and the existence of a double covering. We
      present the construction of band-spinor representations of GL(n,R) in terms of
      Harish-Chandra modules.It is suggested that hadrons interact with gravitation as
      band-spinors of that type. In the metric-affine extension of general relativity,
      the hadron intrinsic hypermomentum is minimally coupled to the connection, in
      addition to the coupling of the energy momentum tensor to the vierbeins. The
      relativistic conservation of intrinsic hypermomentum fits the observed
      regularities of hadrons: SU(6) ( approximately spin independence), scaling, and
      complex-J trajectories. The latter correspond to volume-preserving deformations
      (confinement?) exciting rotational bands.

PMID- 16592444
TI  - Structure of native Renilla reinformis luciferin.
AB  - The structure of native luciferin from the bioluminescent coelenterate Renilla
      reniformis is shown to be 3,7-dihydro-2-(p-hydroxybenzyl)-6-(p-hydroxyphenyl)-8
      benzylimidazo[1,2-a]pyrazin-3-one by mass spectral analysis of synthetic
      luciferin and the luciferin derived from a protein directly involved in the
      bioluminescent system. A previous report of the molecular weight of luciferin is
      shown to be incorrect by reexamination of the spectral data and by synthesis of
      two derivatives. Detailed analysis of kinetic, emission, and quantum yield data
      for the isolated and synthetic luciferins confirms this structure. Confirmation
      of this structure in a number of species from different phyla suggests a common
      substrate for a variety of bioluminescent marine organisms.

PMID- 16592445
TI  - New pathway for the metabolism of pentitols.
AB  - Certain strains of Lactobacillus casei can grow at the expense of one or more
      pentitols. These microorganisms possess a pentitol phosphate pathway that appears
      to be analogous to the hexitol phosphate pathway found in many facultatively
      anaerobic bacteria. Pentitol is transported into the cell by a phospho
      enolpyruvate phosphotransferase system that converts it to pentitol phosphate,
      whereupon a specific dehydrogenase oxidizes the intermediate product to
      ketopentose phosphate. The ketopentose phosphate is subsequently converted to
      xylulose-5-P and enters one of the pathways of central metabolism.

PMID- 16592446
TI  - DNA sequence organization in the water mold Achlya.
AB  - Experiments are described that characterize the organization of DNA sequences in
      the water mold Achlya bisexualis. These experiments demonstrate that repetitive
      and single copy sequences in the Achlya genome are arranged in a long-period
      interspersion pattern. Estimates of the spacing intervals between repetitive and
      single copy DNA indicate, however, that the interspersion pattern in Achlya is
      longer than has been previously reported in other eukaryotes. These data and
      measurements of structural gene expression in Achlya [Timberlake, W.E., Shumard,
      D. S. & Goldberg, R. B. (1977) Cell 10, 623-632] make it difficult to propose a
      regulatory function for repeated DNA in this eukaryote.

PMID- 16592447
TI  - Developmental defects associated with glucosamine auxotrophy in Saccharomyces
      cerevisiae.
AB  - Saccharomyces cerevisiae mutants, unable to make D-glucosamine owing to a defect
      in the enzyme 2-amino-2-deoxy-D-glucose-6-phosphate ketol-isomerase (amino
      transferring) (EC 5.3.1.19), show aberrations both in sporulation and in
      vegetative growth. They grow normally on a medium of yeast extract, peptone, and
      dextrose (YEPD) containing D-glucosamine (1 mg/ml), and such cells accumulate 4
      to 5 times the amount of D-glucosamine present in wild-type cells cultured on
      YEPD alone. When such mutant cells are shifted to YEPD alone, they continue to
      increase in cell mass for about 10 hr (three to four cell cycles) and produce
      strings of beads in which the cells fail to separate. Although each of the
      "cells" contains a nucleus, electron micrographs of thin sections reveal that
      septation is defective apparently owing to the inability to synthesize chitin,
      which forms the primary septum in S. cerevisiae. The viability of such cultures
      drops rapidly after 3-5 hr, a fact attributable to lysis of the cells through
      wall defects in the septum region where gross disorganization is apparent. When
      the mutant cells grown on YEPD plus D-glucosamine are transferred to sporulation
      medium (1% potassium acetate), they proceed through meiosis to produce viable
      spores that appear to be altered only in the nature of the spore wall. The spores
      lack a dark-staining surface layer that is visible in thin sections prepared from
      wild-type cells, they are notably less hydrophobic than wild-type spores, and
      they are digested and lysed by glucanases that do not affect normal spores. All
      of these properties suggest that D-glucosamine is required for spore maturation
      and is used to synthesize a glucanase-resistant hydrophobic surface layer on the
      primary glucan spore wall. In agreement with this postulate, D-glucosamine
      synthesis and the activity of the isomerase do not appear until late in meiosis
      when tetranucleate cells are abundantly present in the sporulation culture.

PMID- 16592448
TI  - Simultaneous measurements of viscosity and density in solutions undergoing
      change.
AB  - The magnetic suspension densimeter-viscometer has been modified so that the
      variations of viscosity and density in solutions undergoing change are determined
      continuously as a function of time. The changes in values for both of these
      properties are also obtained when solutions of varying composition are passed
      through the sample cell (<0.5 ml). The new method measures the torque on the
      magnetically suspended buoy which is held stationary in a stable velocity
      gradient; this procedure also facilitates the measurement of the density with
      greater accuracy. Preliminary results relating to the conformation changes of
      ribonuclease A in the presence of guanidinium chloride and a disulfide cleaving
      agent are presented.

PMID- 16592449
TI  - Organic acid and potassium accumulation in guard cells during stomatal opening.
AB  - Leaflets of Vicia faba L. with either open or closed stomata were quick-frozen
      and freeze-dried. Individual guard cell pairs and pure samples of palisade
      parenchyma, spongy parenchyma, and epidermis lacking guard cells were dissected
      from the leaflets, weighed, and assayed for organic acids or K(+).K(+) was
      measured by a new enzymatic method. In guard cells of open stomata, as compared
      to closed stomata, K(+) was 2- to 4-fold higher, malic acid 6-fold higher, and
      citric acid 3-fold higher. Both aspartic and glutamic acids were also higher, but
      the amounts present were low compared to malic and citric acids. Isocitric acid
      was significantly higher in one experiment, but not in another. Glyceric acid was
      not increased. Succinic acid was too low to detect by the method used; but in
      guard cells of open stomata the concentration must have been less than 2% of that
      of malic acid. Malic acid was higher in the palisade parenchyma from the leaflet
      with open stomata. The ion balance shows that malic and citric acids provide much
      of the counter ion for the K(+) taken up during stomatal opening.

PMID- 16592450
TI  - Use of I-labeled phytochrome to quantitate phytochrome binding to membranes of
      Avena sativa.
AB  - Purified oat phytochrome was labeled with (125)I without altering the
      photoreversibility or absorbance properties of the pigment. The radiolabeled
      phytochrome was used in experiments in vitro to quantitate the binding of the
      pigment to both crude and purified membrane preparations from oat tissue. After
      the membranes were allowed to react with (125)I-labeled phytochrome, washed free
      of unbound material, and pelleted, they were found to have significant levels of
      radioactivity bound to them. Qualitative identification of phytochrome as the
      bound radioactive species was confirmed by autoradiography of sodium dodecyl
      sulfate gels after electrophoresis of the proteins contained in the washed
      membranes. Data supporting the specificity of the binding are that the binding
      shows saturation kinetics and that unlabeled phytochrome, but not bovine serum
      albumin, will competitively inhibit the binding of labeled phytochrome. This
      technique permits the detection of less than a nanogram of phytochrome and
      provides a new method for quantifying bound phytochrome that is independent of
      the spectral detectability of the pigment. It should be useful in elucidating the
      nature of phytochrome attachment to cellular membranes.

PMID- 16592451
TI  - Food webs and the dimensionality of trophic niche space.
AB  - If the trophic niche of a kind of organism is a connected region in niche space,
      then it is possible for trophic niche overlaps to be described in a one
      dimensional niche space if and only if the trophic niche overlap graph is an
      interval graph. An analysis of 30 food webs, using the combinatorial theory of
      interval graphs, suggests that a niche space of dimension 1 suffices, with
      unexpectedly high frequency and perhaps always, to describe the trophic niche
      overlaps implied by real food webs in single habitats. Consequently, real food
      webs fall in a small subset of the set of mathematically possible food webs. That
      real food webs are compatible with one-dimensional trophic niche spaces, more
      often than can be explained by chance alone, has not been noticed previously.

PMID- 16592452
TI  - Classification of methanogenic bacteria by 16S ribosomal RNA characterization.
AB  - The 16S ribosomal RNAs from 10 species of methanogenic bacteria have been
      characterized in terms of the oligonucleotides produced by T(1) RNase digestion.
      Comparative analysis of these data reveals the methanogens to constitute a
      distinct phylogenetic group containing two major divisions. These organisms
      appear to be only distantly related to typical bacteria.

PMID- 16592453
TI  - How does selection reconcile individual advantage with the good of the group?
AB  - An individual's advantage often conflicts with the good of its group, as when an
      allele spreads by meiotic drive through a population whose death rate it
      increases, or when an asexual genotype derives immediate advantage at the expense
      of future adaptability. We show how selection within populations may reconcile
      individual and group advantage, as in the evolution of "honest meioses" resistant
      to segregation distortion, and the avoidance of the "cost of sex." Selection
      between species, whose evolutionary importance we document, presumably favors the
      survival and multiplication of species whose genetic systems or social
      organizations favor the evolution of mechanisms reconciling individual with group
      advantage: in other words, species with genetic or social systems where a gene's
      long-term selective advantage most nearly matches its contribution to the good of
      the species.

PMID- 16592454
TI  - Size-mediated onset of genetically determined maturation in the platyfish,
      Xiphophorus maculatus.
AB  - A single sex-lined gene that controls the maturation process had previously been
      identified in Xiphophorus maculatus. It was presumed that this gene controls the
      age of onset of maturation. We demonstrate that the gene is either activated or
      not inhibited from activity by the attainment of a critical weight rather than
      age.

PMID- 16592455
TI  - Perturbation of chloroplast DNA amounts and chloroplast gene transmission in
      Chlamydomonas reinhardtii by 5-fluorodeoxyuridine.
AB  - 5-Fluorodeoxyuridine selectively decreases the rate of chloroplast DNA
      replication in Chlamydomonas resulting after several generations of growth in
      equilibrium levels as low as one-seventh of normal. When the maternal parent is
      treated prior to mating, the decrease of chloroplast DNA appears to perturb the
      normal maternal transmission of chloroplast genes, dramatically increasing the
      proportion of exceptional zygotes transmitting chloroplast genes from the
      paternal parent.

PMID- 16592456
TI  - Evolution of primate oncornaviruses: An endogenous virus from langurs (Presbytis
      spp.) with related virogene sequences in other Old World monkeys.
AB  - Gene sequences related to a retrovirus (oncornavirus type D) isolated from a lung
      cell culture from spectacled langur (Presbytis obscurus) are found in multiple
      copies (20-40 per haploid genome) in langur cellular DNA; partially homologous
      virogene sequences are present in the DNA of related Old World monkey species.
      Primates thus contain gene sequences for at least two distinct classes of
      genetically transmitted oncornaviruses, the type C class (isolated from baboons)
      and the type D class described here. The langur virus is partially related to
      Mason-Pfizer monkey virus, a type D retrovirus isolated from rhesus monkeys.
      Nucleic acid hybridization studies suggest that Mason-Pfizer monkey virus, now
      infectious among primates, was derived from an endogenous virus of langurs or
      from another member of the primate sub-family Colobinae.

PMID- 16592457
TI  - Calcitonin: Its hormonal action on the gill.
AB  - When isolated salmon gills were perfused under simulated in vivo conditions,
      norepinephrine increased and calcitonin decreased the rate of flow of perfusate
      and the influx of calcium and phosphate through the gill. Only the increased
      water flow was mediated by beta-adrenergic receptors. Differences in sensitivity
      to both hormones were observed with gills from prespawning and postspawning
      salmon; gills from freshwater-adapted fish were less sensitive to norepinephrine
      and more sensitive to calcitonin, suggesting a decreased production of this
      hormone in the late stage of the life cycle. The antagonistic effects of
      calcitonin and norepinephrine on the gill strongly implicate their regulatory
      role for calcium homeostasis in vivo; the major process being regulated is the
      influx of calcium into the gill. In fish, calcitonin performs an important role
      in regulating gill function.

PMID- 16592458
TI  - Role of ecdysone, pupariation factors, and cyclic AMP in formation and tanning of
      the puparium of the fleshfly Sarcophaga bullata.
AB  - Two pupariation factors, anterior retraction factor (ARF) and puparium tanning
      factor (PTF), are absent from the hemolymph of larvae at the time of tanning
      accelerated by ARF/PTF, cyclic AMP, or dopamine. ARF and PTF are not involved in
      derepression of dopa decarboxylase (aromatic L-amino-acid decarboxylase, aromatic
      L-amino-acid carboxy-lyase, EC 4.1.1.28) synthesis initiated by ecdysone. Tanning
      is entirely inhibited by injection of two transcriptional inhibitors, actinomycin
      and BrdUrd, and two translational inhibitors, puromycin and cycloheximide.
      Retraction activity is more severely inhibited by the transcriptional than by the
      translational inhibitors. A tanning response is initiated by cyclic AMP in the
      presence of the transcriptional but not the translational inhibitors. Dihydric
      tanning substances (dopa, dopamine) initiate tanning in the presence of both
      types of inhibitors. Release of ARF and PTF from the central nervous system is
      inhibited by the four inhibitors. ARF totally reverses the inhibitory effects on
      retraction, whereas PTF does not reverse inhibition of tanning. These data are
      interpreted to mean that PTF is concerned with the regulation of two components
      of the tanning response: (i) acceleration of synthesis of a particular protein
      (associated with the tyrosine hydroxylation complex), and (ii) activation via
      cyclic AMP of a component of the tyrosine hydroxylating system.

PMID- 16592459
TI  - Theory of connectivity for formally symmetric operators.
AB  - A previous paper introduced the notion of complete connectivity conditions and
      developed variational principles for diffraction problems subjected to such
      restrictions. Here, an abstract definition of formally symmetric operators is
      given and it is shown that the problem of connecting solutions of equations
      associated with this kind of operators leads to complete connectivity conditions.
      The variational principles previously developed as well as a present more general
      one are thus applicable. The problem of connecting solutions defined in different
      regions is basic for finite element formulations. Formally symmetric operators
      occur in many branches of science and engineering. Applications are given here to
      potential theory, wave propagation, elasticity, and a general class of boundary
      integral equations.

PMID- 16592460
TI  - Discrete spiral modes in disk galaxies: Some numerical examples based on density
      wave theory.
AB  - Discrete growing spiral modes are calculated, on the basis of principles of
      stellar dynamics, according to the recently developed asymptotic theory of
      density waves for spiral structure in galaxies. From the growth rates obtained,
      it appears likely that several spiral modes coexist in a given disk galaxy.
      General properties of these modes are described for two galaxy models, and some
      of their important observational implications are discussed.

PMID- 16592461
TI  - A valid model for the mechanism of oxidation of tryptophan to formylkynurenine-25
      years later.
AB  - The dye-sensitized photooxygenation of DL-tryptophan in aqueous solution leads to
      the tricyclic compound 2-carboxy-3a-hydroperoxy-1,2,3,3a,8,8a
      hexahydropyrrolo[2,3-b]indole which, on reduction with dimethyl sulfide,
      furnishes two diastereoisomeric alcohols separable by fractional crystallization
      into a higher melting (mp 254 degrees -256 degrees ) and a lower melting (mp 228
      degrees ) diastereoisomer. Each of these alcohols was correlated with one of the
      analogous pair of isomeric 1,2-dicarbomethoxy analogs by alkaline hydrolysis and
      by x-ray analysis. In this way, the 3a-hydroxy-1,2-dimethoxycarbonyl-
      1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole, mp 163 degrees -164 degrees , was
      shown to have the trans configuration with regard to the relative positions of
      the hydroxyl and carbomethoxy groups and that, on alkaline hydrolysis, it
      produced the isomer with mp 228 degrees , which therefore also has the trans
      configuration. The mechanism of the smooth thermal rearrangement of the
      (presumably ring-chain tautomeric) tryptophan hydroperoxy intermediates to
      formylkynurenine is discussed with its implications for the biological oxidation
      by tryptophan 2,3-dioxygenase.

PMID- 16592462
TI  - Biogenic amine-ionophore interactions: Structure and dynamics of lasalocid
      (X537A) complexes with phenethylamines and catecholamines in nonpolar solution.
AB  - The ionophore lasalocid A forms 1:1 complexes with phenethylamines (1-amino-1
      phenylethane and 1-amino-2-phenylethane) and catecholamines (dopamine and
      norepinephrine) in nonpolar solution. We have undertaken high-resolution proton
      nuclear magnetic resonance studies to deduce structural and kinetic information
      on the ionophore-biogenic amine complexes in chloroform solution. The coupling
      constant, chemical shift, and relaxation time data demonstrate that the lasalocid
      backbone conformation and the primary amine binding sites in the complexes are
      similar to those determined earlier for the alkali and alkaline earth complexes
      of this ionophore in solution. The exchange of lasalocid between the free acid
      (HX) and the primary amine complexes (RNH(3)X) in chloroform solution have been
      evaluated from the temperature-dependent line shapes at superconducting fields.
      The kinetic parameters associated with the unimolecular dissociation [Formula:
      see text] and the bimolecular exchange [Formula: see text] reactions have been
      deduced from an analysis of the lifetime of the complex as a function of the
      reactant concentrations. The relative stability of the complex decreases in the
      order phenyl > n-pentyl for substituents on the carbon alpha to the amino group
      (1-amino-1-phenylethane and 2-aminoheptane) and phenyl > 3,4-dihydroxyphenyl for
      substituents on the carbon beta to the amino group (1-amino-2-phenylethane and
      dopamine). These results suggest that nonpolar interactions between the biogenic
      amine side chain and the lasalocid molecule contribute to the stability of the
      complex in solution.

PMID- 16592463
TI  - Significant structure theory applied to liquid helium-3.
AB  - The significant structure theory of liquids is successfully applied to the
      quantum liquid (3)He. The partition function uses the Debye partition function
      for the solid-like molecules and the Fermi-Dirac partition function for the gas
      like degrees of freedom. To evaluate the gas-like partition function, numerical
      calculations are performed and some integral functions appearing in the equation
      of state of the ideal Fermi-Dirac gas are tabulated. In the solid-like molecules,
      the molar volume V(s) depends on the temperature, and a linear dependence is
      used.The thermodynamic properties, such as molar volume, vapor pressure, entropy,
      heat capacity, and the critical constants as well as the surface tension of
      liquid (3)He are calculated. The agreement between theory and experiment is
      satisfactory.

PMID- 16592464
TI  - Transient magnetic effects in a scale model of the earth's core.
AB  - Scale model experiments are described in which the contribution to the dipole
      magnetic field of a conducting sphere (simulating the earth's core) by initially
      closed, internal flux loops is measured. A magnetic loop is maintained by
      constant current in a toroidal coil, in a mercury sphere. The circuit is then
      opened, which allows the magnetic loop to diffuse and dissipate. The time
      development of the magnetic effects outside the sphere is recorded, especially
      the contribution in the dipole mode of the sphere. In a sample application of the
      result, a doughnut-shaped flux loop, of major and minor radii 0.17 and 0.053 R(c)
      (R(c) = earth's core radius) and centered at 0.68 R(c), of field strength 100
      gauss, in optimal orientation and in a core of conductivity 3 x 10(-6) emu is
      assumed. If one such flux loop is set free on the average of every 40 years, the
      earth's dipole field is maintained. The relative intensity of the short-lived
      nondipole component that would accompany the process in the simplified example is
      estimated from the data and found not to be inconsistent with that observed in
      the real earth. Only the basic process of the feeding of a poloidal field by
      initially closed free flux loops in a static conducting sphere is investigated.
      The requirement that, in a real situation, the loops would have to be set free in
      a preferred orientation is discussed, and an existing model of a system that in
      some degree answers the requirement is cited.

PMID- 16592465
TI  - On a sharpened form of the Schauder fixed-point theorem.
AB  - If K is a compact convex subset of a locally convex topological vector space X,
      we consider a continuous mapping f of K into X. A fixed-point theorem is proved
      for such a map f under the assumption that for a given continuous realvalued
      function p on K x X with p(x,y) convex in y and for each point x in K not fixed
      by f, there exists a point y in the inward set I(K)(x) generated by K at x with
      p(x,y - f(x)) less than p(x,x - f(x)). For X a Banach space, in particular, this
      yields a sharp extension and a drastic simplification of the fixed point theory
      of weakly inward (and weakly outward) mappings. The result comes close in the
      domain of mappings of compact convex sets to the thrust of fixed point conditions
      of the Leray-Schauder type for compact maps of sets with interior in X.

PMID- 16592466
TI  - Roles of ecdysone in Drosophila development.
AB  - A temperature-sensitive lethal mutant of Drosophila melanogaster called ecd(1)
      becomes deficient in ecdysone, as measured by a radioimmunoassay, when there is a
      shift in temperature from 20 degrees to 29 degrees at various stages of
      development. Associated with the ecdysone deficiency at 29 degrees , there are
      abnormalities in larval and imaginal development and the adult functions. When
      the shift occurs early in third-instar stage, the mutant larvae grow to full size
      but fail to pupariate, and instead remain living larvae for as long as 3 weeks.
      These larvae, which have only about 5% as much ecdysone as the wild-type at the
      time of pupariation, can be induced to pupariate at 29 degrees by ecdysone in
      their food, indicating that the pupariation block results from an ecdysone
      deficiency. A shift to 29 degrees later in the third-instar stage does not
      prevent pupariation of the mutant, but the imaginal discs fail to complete
      differentiation, although the discs can differentiate at 29 degrees after
      transplantation to the normal environment of a wild-type host. A shift to 29
      degrees early in the first-instar stage blocks a subsequent rise in ecdysone
      titer and results in extensive developmental defects. Mutant adults become
      sterile at 29 degrees , and the ecdysone titer in the females concomitantly
      decreases to 13% of the wild-type value. Mutant larval ovaries transplanted to
      wild-type female hosts continue to develop and produce competent eggs at 20
      degrees , but when the adult hosts are put at 29 degrees the transplanted ovaries
      become sterile, suggesting that the ecdysone needed for female fertility is
      synthesized autonomously by ovarian tissue. In contrast to these effects of a
      shift to 29 degrees during larval, pupal, and adult stages, there is a normal
      increase in ecdysone titer and normal development in mutant embryos grown at 29
      degrees . The insensitivity of the embryo to the ecd(1) mutation might be due to
      a maternal contribution of components needed for ecdysone synthesis during the
      embryonic stage.

PMID- 16592467
TI  - Inheritance of selected pathotoxin resistance in maize plants regenerated from
      cell cultures.
AB  - Texas male-sterile cytoplasm (cms-T) maize is susceptible to Helminthosporium
      maydis race T and its pathotoxin, whereas nonsterile cytoplasm maize is
      resistant. Callus cultures initiated from immature embryos of a cms-T genotype,
      BC(1)A188(T), were susceptible to the toxin and were capable of plant
      regeneration. Toxin-resistant cell lines were selected by a sublethal enrichment
      procedure in which cms-T callus was grown for several selection cycles
      (subculture transfers) in the presence of progressively higher concentrations of
      toxin. Periodically during the selection process, plants were regenerated from
      the cms-T cultures to determine their susceptibility or resistance to the toxin.
      Plants regenerated after four cycles of selection were male-sterile and toxin
      susceptible as shown by leaf bioassays. All plants regenerated from cell lines
      isolated from the fifth selection cycle onward, however, were toxin-resistant and
      52 of 65 were fully male-fertile. The remaining 13 "male-sterile" resistant
      plants did not shed pollen and did not resemble cms-T plants in tassel
      morphology. Some "male-sterile" plants produced anthers containing a small amount
      of starch-filled pollen, suggesting that the sterility of these 13 plants was not
      the result of the cms-T trait. Leaf bioassays on F(1) progeny from regenerated
      resistant plants indicated that resistance to the toxin was inherited only
      through the female. The male-fertility trait also was inherited only through the
      female. After inoculation with H. maydis race T spores, leaf lesion size for
      progeny from regenerated resistant plants coincided with their reaction to the
      toxin. This result indicated that plant resistance to the pathogen was closely
      correlated with the toxin resistance obtained through cell culture selection.

PMID- 16592468
TI  - Chemical compositions of Magellanic Clouds' HII regions based on photoelectric
      spectrophotometry.
AB  - Detailed line intensity measurements secured at Cerro Tololo Interamerican
      Observatory and corrected for interstellar extinction are presented for 19 HII
      regions in the Large Magellanic Cloud and 6 in the Small Magellanic Cloud. The
      elemental abundances derived by simple methods appear to be in good accord with
      those found by other observers. Detailed discussion is deferred to a later paper.

PMID- 16592469
TI  - C nuclear magnetic resonance study of five- and six-coordinated carbon in
      nonclassical organometallic compounds: Dimeric trialkyl-, tricyclopropyl-, and
      triarylaluminums and some nido and closo carboranes.
AB  - A (13)C nuclear magnetic resonance spectroscopic study of dimeric trimethyl-,
      triethyl-, tricyclopropyl-, and triarylaluminums is reported. The five
      coordinated bridging carbons are found consistently more shielded than the
      terminal carbons, in accordance with the increased p-character of the former. The
      nature of bridging two-electron three-centered Al-C-Al bonds is discussed. (13)C
      nuclear magnetic resonance shifts of several nido and closo carboranes containing
      five and six coordinated carbons and their (13)C-(1)H spin-spin coupling
      constants were also obtained. The relationship between the carbon chemical shifts
      and coordination number of the carbon atom is discussed. There is approximately a
      20- to 40-ppm shielding of the (13)C chemical shifts of five- and six-coordinated
      carbons, compared with those of four valent carbons, with a simultaneous general
      increase of J(C-H) coupling constants.

PMID- 16592470
TI  - Structure of transition-metal cluster compounds: Use of an additional orbital
      resulting from the f, g character of spd bond orbitals.
AB  - A general theory of the structure of complexes of the transition metals is
      developed on the basis of the enneacovalence of the metals and the requirements
      of the electroneutrality principle. An extra orbital may be provided through the
      small but not negligible amount of f and g character of spd bond orbitals, and an
      extra electron or electron pair may be accepted in this orbital for a single
      metal or a cluster to neutralize the positive electric charge resulting from the
      partial ionic character of the bonds with ligands, such as the carbonyl group.
      Examples of cluster compounds of cobalt, ruthenium, rhodium, osmium, and gold are
      discussed.

PMID- 16592471
TI  - A reducibility criterion for generalized principal series.
AB  - We give necessary and sufficient conditions for the reducibility of
      representations of semisimple Lie groups induced from discrete series
      representations of parabolic subgroups, when the inducing parameters are
      nonsingular.

PMID- 16592472
TI  - Minimal coupling and the symplectic mechanics of a classical particle in the
      presence of a Yang-Mills field.
AB  - This note is to show how to use symplectic geometry to write equations of motion
      of a "classical particle" in the presence of a Yang-Mills field, for any gauge
      group, G, and any differentiable manifold, M. In the case that M is Minkowski
      space and G = U(1), the equations reduce to the Lorentz equations for a charged
      particle in an electromagnetic field. Our procedure in the general case uses the
      connection form as defined on the principle bundle to introduce a symplectic
      structure on certain associated bundles and is automatically gauge invariant.

PMID- 16592473
TI  - Maize chloroplast DNA fragment encoding the large subunit of ribulosebisphosphate
      carboxylase.
AB  - In vitro linked transcription-translation of chloroplast DNA has been used to
      show that the large subunit of ribulose-1,5-bisphosphate carboxylase [3-phospho-D
      glycerate carboxy-lyase (dimerizing), EC 4.1.1.39] is encoded by Zea mays
      chloroplast DNA. A BamHI-generated chloroplast DNA sequence cloned in Escherichia
      coli is shown to direct the in vitro synthesis of this protein identified as
      large subunit by its size, serological properties, and limited proteolytic
      digestion products.

PMID- 16592474
TI  - Controlling element-induced alterations in UDPglucose:flavonoid
      glucosyltransferase, the enzyme specified by the bronze locus in maize.
AB  - The bz locus in maize, which directs synthesis of the enzyme UDPglucose:flavonoid
      glucosyltransferase (UFGT) in the endosperm, is one of many loci at which
      controlling element-induced phenotypic changes are known. To characterize the
      nature of such modifications, several bz mutants derived by transposition of the
      controlling element Ds to the Bz gene were analyzed. Three mutants were found to
      lack UFGT at all stages of endosperm development. Two others appeared to make an
      altered UFGT, and in one of these the enzyme showed an altered developmental
      profile.

PMID- 16592475
TI  - Generalizing Fisher's "reproductive value": Nonlinear, homogeneous, biparental
      systems.
AB  - Biparental demographic models violate linearity. However, in their early "dilute"
      stages before limited environment resources bring need for competitive selection,
      first-degree-homogeneous relations obtain. For them, a reproductive-value
      function of the initial coordinates is defined to recapitulate their contribution
      to the asymptotically dominating mode of exponential growth: now the generalized
      Fisher reproductive value of one sex is altered by relative numbers of the other
      sex. The new reproductive-value function is also derived for general systems of
      homogeneous-first-degree differential and difference equations, and is shown to
      grow from the start at the asymptotic growth rate.

PMID- 16592476
TI  - Chemical composition of gaseous nebula NGC 6302.
AB  - The irregular emission nebula NGC 6302 exhibits a rich spectrum of lines ranging
      in excitation from [NI] to [FeVII]. An assessment of available spectroscopic
      data, covering a large intensity range, indicates excess of helium and nitrogen
      as compared with average planetary nebulae, but deficiencies in iron and calcium.
      These metals are presumably tied up in solid grains, as suggested by Shields for
      iron in NGC 7027.

PMID- 16592477
TI  - Bond angles in transition-metal tricarbonyl compounds: A test of the theory of
      hybrid bond orbitals.
AB  - The theory of hybrid bond orbitals is used to calculate equations giving the
      value of the bond angle OC-M-CO in relation to the bond number of the metal
      carbonyl bond for tricarbonyl groups in which the transition-metal atom is
      enneacovalent or octacovalent and the group has approximate trigonal symmetry.
      For cobalt and iron and their congeners the average experimental values lie
      within about 1 degrees of the theoretical values for enneacovalence, which are
      101.9 degrees for Co(CO)(3) and 94.5 degrees for Fe(CO)(3). This agreement
      provides strong support for the theory. For Mn(CO)(3) and Cr(CO)(3) the
      experimental values indicate the average covalence to be about 8.4 and 7.7,
      respectively, in agreement with considerations based on the electroneutrality
      principle.

PMID- 16592478
TI  - Paired ions: Dipolar pairs as subset of diffusion pairs.
AB  - Previous models for which theories of electrolytic conductance have been
      developed are reviewed. Discrepancies between theoretically derived values of
      parameters and parameters characteristic of real physical systems suggested the
      following revised model. Ions are counted as diffusion pairs if their center-to
      center distance r is in the range a </= r </= R, in which a is contact distance
      and R is the diameter of the Gurney cosphere. A fraction alpha of these pairs
      diffuse to contact to form nonconducting dipolar pairs; alpha/(1-alpha) = exp(
      E(s)/kT), in which E(s) is the difference in energy between a diffusion pair at r
      = R and a contact pair, k is the Boltzmann constant, and T is the absolute
      temperature. This model permits separate treatment of long-range and short-range
      interionic effects. The former (relaxation field and electrophoresis) depend on R
      and the values of the dielectric constant and viscosity of the pure solvent. The
      latter (formation of dipolar pairs) is described by E(s), or alternatively by
      K(s) = exp(-E(s)/kT) in which K(s) is the constant describing the steady state
      between solvent-separated diffusion pairs and dipolar (contact) pairs. For
      solutions of the alkali halides, a simple empirical correlation is found between
      R and the Pauling radii of the cations, and also between E(s) and the sum of the
      radii of cation and anion.

PMID- 16592479
TI  - Specificity of the juvenile hormone binding protein: The geometrical isomers of
      juvenile hormone I.
AB  - The binding of the geometrical isomers (>/=99% pure) of juvenile hormone I to the
      hemolymph juvenile hormone binding protein of Manduca sexta (Lepidoptera,
      Sphingidae) was analyzed. A technique is described for isomer separation by
      micropreparative high-resolution liquid chromatography. Analysis of competition
      was performed by using a "batch adsorption" hydroxylapatite binding assay.
      Competition studies indicate that the naturally occurring isomer, 2E,6E,10cis, is
      bound with the highest affinity. Optimal binding appears to depend most heavily
      upon the configuration of the 2,3 double bond. Juvenile hormone binding protein
      shows a higher affinity for the 2E than for the 2Z configuration. The 6,7 double
      bond is of less importance in determining binding activity, and isomerism about
      the epoxide appears least important in conferring binding activity. The binding
      site may be a groove along the surface of the binding protein interacting with
      the side chains of juvenile hormone, including the ester methyl group. The
      grouping of the side chains and the ester methyl group thus constitutes a
      distinct hydrophobic face, and the hydrophobic interactions are essential in
      maintenance of the bound ligand.

PMID- 16592480
TI  - On some global problems of geophysical fluid dynamics (A Review).

PMID- 16592481
TI  - A geometric model describing a quasi-equilibrium of energy flow in populations of
      stream insects.
AB  - Studies of growth, population structure, and metabolism for the mayfly nymph
      Ephemerella dorothea suggest that in natural streams this species maintains a
      nearly uniform weight-specific metabolic rate from the time of hatching (0.002
      mg) to maturity (4.0 mg) as average stream temperature increases from 0.5 degrees
      to 15 degrees . The observed homeostasis represents a central tendency between
      two opposing factors that affect metabolism (size and temperature) and is
      achieved because any increase in metabolic rate due to warming of streams from
      winter to late spring is almost completely compensated by the increase in nymphal
      size from hatching to emergence. Results indicate that natural selective
      processes have favored individuals whose growth rates are proportional to
      seasonal changes in temperature. The model suggests a possible mechanism for
      explaining synchronous larval growth, pulsed adult emergence, and progressive
      decreases in adult weight of individuals emerging after the main cohort.

PMID- 16592482
TI  - Silane/iodine-based cleavage of esters and ethers under neutral conditions.
AB  - New, efficient cleavage of carboxylic esters with iodotrimethylsilane or a
      mixture of phenyltrimethylsilane and iodine is described. Essentially neutral
      conditions can be maintained throughout the reactions. Ethers can be dealkylated
      by the latter method in high yields. The mechanism of the cleavage reactions is
      considered to include six-membered ring homopolar transition states.

PMID- 16592483
TI  - Decision procedure for indefinite hypergeometric summation.
AB  - Given a summand a(n), we seek the "indefinite sum" S(n) determined (within an
      additive constant) by [Formula: see text] or, equivalently, by [Formula: see
      text] An algorithm is exhibited which, given a(n), finds those S(n) with the
      property [Formula: see text] With this algorithm, we can determine, for example,
      the three identities [Formula: see text] [Formula: see text] and [Formula: see
      text] and we can also conclude that [Formula: see text] is inexpressible as S(m) 
      S(0), for any S(n) satisfying Eq. 2.

PMID- 16592484
TI  - Random genetic drift in a cline.
AB  - A diffusion model is derived for random genetic drift in a cline. The monoecious
      organism occupies an unbounded linear habitat with constant, uniform population
      density. Migration is homogeneous, symmetric, and independent of genotype. The
      analysis applies to a single diallelic locus without dominance or mutation.
      Assuming that Hardy-Weinberg proportions obtain locally, partial differential
      equations are deduced for the expected gene frequency at each location and the
      covariance between gene frequencies at any two points of the habitat. For most
      selection gradients, the population density, rho, selection intensity, s, and
      migration variance, sigma(2), appear only combined in the single dimensionless
      parameter, beta, the ratio of the characteristic length for migration and random
      drift to the natural distance for migration and selection. Random drift is highly
      significant if beta << 1; it causes only relatively small variations of order
      1/beta around the deterministic cline if beta >> 1. With beta >> 1, the
      correlation between the gene frequencies at any two points is very nearly
      independent of beta, and hence is parameter-free for particular forms of the
      selection gradient. For a very steep selection gradient, beta = 2 [unk]
      2srhosigma, i.e., essentially the product of the square root of the selection
      intensity and the neighborhood size.

PMID- 16592485
TI  - On unstable cohomology classes of SL(Z).
AB  - From algebraic K-theory, we show that there exists a spectral sequence that has
      real cohomology of SL(n)(Z) as its E(1)-terms and converges to the tensor product
      of a polynomial algebra and an exterior algebra. On the basis of this spectral
      sequence, we discovered several families of real unstable cohomology classes of
      SL(n)(Z).

PMID- 16592486
TI  - Nerve growth factor increases activity of ornithine decarboxylase in rat brain.
AB  - Intraventricular administration of nanogram quantities of nerve growth factor to
      adult rats results in a marked increase in the activity of ornithine
      decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) in the brain. The increase
      occurs in all major brain regions and the activity is maximal by 7.5 hr after
      administration. The enzyme response to nerve growth factor increases in magnitude
      during maturation; the relative increase in ornithine decarboxylase activity in
      adult animals is much greater than that in young. Neither insulin nor bovine
      growth hormone was able to increase ornithine decarboxylase activity to the same
      extent as did nerve growth factor. When brain was separated into neuronal- and
      glial-enriched fractions, induction of ornithine decarboxylase was found in both,
      but a greater increase was observed in the glial fraction.

PMID- 16592487
TI  - Observational validation of the chronometric cosmology: The redshift-magnitude
      relation for quasi-stellar objects.
AB  - A statistical study is made of the redshift-magnitude relation for a recent
      comprehensive catalogue of quasi-stellar objects. The chronometric theory,
      although devoid of free parameters such as the q(0) and Lambda of the expansion
      theory, provides an excellent fit to the observed relation. The expansion theory
      does not provide an empirically meaningful fit.

PMID- 16592488
TI  - Observational model of the ionized gas in Seyfert and radio-galaxy nuclei.
AB  - Equivalent widths of the total emission-line Hbeta in Seyfert 1, Seyfert 2, and
      intermediate-type Seyfert galaxies, expressed in terms of the featureless
      continuum, all have approximately the same frequency distribution. This suggests
      that the energy-input mechanism to both the narrow-line, low-density gas and the
      broad-line, high-density gas is photoionization by the featureless continuum. The
      reason for the weakness of the narrow emission lines in extreme Seyfert 1
      galaxies is then the absorption of most of the ionizing photons in the dense gas
      near the central source. The statistics of line widths can be fitted by a model
      in which the dense gas has typical rotational velocity 5000 km/sec and typical
      turbulent velocity 2000 km/sec. A model is proposed in which the dense gas forms
      a rotating, turbulent disk with dimension approximately 0.1 pc and
      height/diameter approximately 2/5. Seyfert 2 galaxies are objects with little
      dense gas, and intermediate-type Seyfert galaxies are objects in which the dense
      gas is optically thin to ionizing radiation at least along the poles. Most radio
      galaxies have strong narrow emission lines, suggesting that escape of radio
      plasma can only occur where some ionizing photons can also escape from the dense
      gas. Other predictions, implications, and tests of this model are discussed.

PMID- 16592489
TI  - Variation of isomer distribution in electrophilic nitration of toluene, anisole,
      and o-xylene: Independence of high regioselectivity from reactivity of reagent.
AB  - The nitration of toluene and anisole was studied with nitrating systems of
      varying reactivity. High regioselectivity of ortho-para over meta substitution
      was maintained in all nitrations, regardless of the reactivity of the nitrating
      system. At the same time, the amount of meta substitution stayed low (3% or
      less), even when the fast reactions may have reached the encounter-controlled
      limit. Because the nitration of o-xylene, in which both ring positions are
      activated by the effect of a methyl group, also does not show any diminishing of
      regioselectivity, the possibility of a dual mechanistic pathway, in which the
      activated position would react by a fast, encounter-controlled path, whereas the
      nonactivated meta position by a slower sigma-type path, can be ruled out. The
      data unambiguously prove that the high regioselectivity of electrophilic aromatic
      nitration is independent of the reactivity of the reagent, because no significant
      increase of meta substitution of toluene or anisole was observed, regardless of
      the activity of the nitrating system. No selectivity-reactivity relationship is
      thus evident and the ortho-para directing effect of primary substituents over
      meta substitution is always maintained. The variation in the amount of the meta
      isomer, up to the observed limit of about 3% in the case of toluene and <2% for
      anisole, is probably significant but, at the present time, cannot be
      quantitatively evaluated with the +/-0.5% overall reproducible accuracy of the
      nitrations. Steric factors, such as increasing bulkiness of the nitrating agent,
      also can affect the ortho-para isomer ratios but are not considered to be the
      only reason for the observed variations, which reflect the specific nitrating
      systems, affecting the nature and position of the transition state of highest
      energy on the reaction pathway.

PMID- 16592490
TI  - Bond angles in transition metal tetracarbonyl compounds: A further test of the
      theory of hybrid bond orbitals.
AB  - An equation for the bond angles OC-M-CO for tetracarbonyl groups in which the
      transition metal atom M is enneacovalent, derived from the simple theory of
      hybrid sp(3)d(5) bond orbitals, is tested by comparison of the calculated values
      of the angles with the experimental values reported for many compounds containing
      M(CO)(4) groups, especially those with M = Fe, Mn, Re, Cr, or Mo. The importance
      of the energy of resonance of single bonds and double bonds in stabilizing
      octahedral complexes of chromium and manganese with carbonyl, phosphine, arsine,
      and thio groups is also discussed.

PMID- 16592491
TI  - Lie algebras and classical partition identities.
AB  - In this paper we interpret Macdonald's unspecialized identities as multivariable
      vector partition theorems and we relate the well-known Rogers-Ramanujan partition
      identities to the Weyl-Kac character formula for an infinite-dimensional
      Euclidean generalized Cartan matrix Lie algebra.

PMID- 16592492
TI  - On localization for double Fourier series.
AB  - The localization theorems for Fourier series of functions of a single variable
      are classical and easy to prove. The situation is different for Fourier series of
      functions of several variables, even if one restricts consideration to
      rectangular, in particular square, partial sums. We show that the answer to the
      problem can be obtained by considering the notion of generalized bounded
      variation, which we introduced. Given a nondecreasing sequence {lambda(n)} of
      positive numbers such that Sigma 1/lambda(n) diverges, a function g defined on an
      interval I of R(1) is said to be of Lambda-bounded variation (LambdaBV) if
      Sigma|g(a(n)) - g(b(n))|/lambda(n) converges for every sequence of nonoverlapping
      intervals (a(n), b(n)) [unk]I. If lambda(n) = n, we say that g is of harmonic
      bounded variation (HBV). The definition suitably modified can be extended to
      functions of several variables. We show that in the case of two variables the
      localization principle holds for rectangular partial sums if LambdaBV = HBV, and
      that if LambdaBV is not contained in HBV, then the localization principle does
      not hold for LambdaBV even in the case of square partial sums.

PMID- 16592493
TI  - A new class of pseudo-differential operators.
AB  - We describe a class of pseudo-differential operators and their singular integral
      realizations and show how these may be used to give precise estimates in various
      function spaces. Application will be given in particular to several situations in
      which subelliptic estimates arise for partial differential equations.

PMID- 16592494
TI  - Adaptive design in regression and control.
AB  - When y = M(x) + epsilon, where M may be nonlinear, adaptive regression designs of
      the levels x(1), x(2),... at which y(1), y(2),... are observed lead to
      asymptotically efficient estimates of the value theta of x for which M(theta) is
      equal to any desired value y(*). More importantly, these designs also make the
      "cost" of the observations, defined at the nth stage to be Sigma(1) (n) (x(i) -
      theta)(2), to be of the order of log n instead of n, an obvious advantage in
      medical and other applications.

PMID- 16592495
TI  - Cell-free synthesis of leaf protein: Identification of an apparent precursor of
      the small subunit of ribulose-1,5-bisphosphate carboxylase.
AB  - Cytoplasmic mRNA has been isolated from the leaves of pea seedlings. Translation
      of this RNA in the wheat germ cell-free system produces two major products, RI
      and RII, with molecular weights of 33,000 and 20,000, respectively. Both of these
      products are considerably larger than the small subunit of ribulose-1,5
      bisphosphate carboxylase [3-phospho-D-glycerate carboxy-lyase (dimerizing), EC
      4.1.1.39], which is the major product of cytoplasmic protein synthesis in vivo
      and has a molecular weight of 14,000. Antiserum prepared against the small
      subunit of ribulose-1,5-bisphosphate carboxylase precipitates from the cell-free
      products, in 2-3% yield, three polypeptides of molecular weights 18,000, 16,000
      and 14,000. The smallest of these polypeptides is indistinguishable, by sodium
      dodecyl sulfate/polyacrylamide gel electrophoresis, from the small subunit of
      ribulose-1,5-bisphosphate carboxylase. Although the cell-free product RII is not
      precipitated with antiserum prepared against the small subunit of ribulose-1,5
      bisphosphate carboxylase, the two polypeptides do show extensive sequence
      homology, as indicated by ion exchange chromatography of their tryptic peptides.
      The production of RII can also be achieved in a polysome-primed cell-free system,
      where protein synthesis is restricted to the completion of polypeptide chains
      that have already been initiated in vivo. These results indicate that RII is
      apparently a precursor of the small subunit of ribulose-1,5-bisphosphate
      carboxylase. We suggest that the selective transport of cytoplasmically
      synthesized organelle proteins, like animal secretory proteins, may be achieved
      via the production of precursor polypeptides.

PMID- 16592496
TI  - Purification and translation of zein messenger RNA from maize endosperm protein
      bodies.
AB  - The messenger RNAs coding for the zein storage protein have been purified from
      other contaminating RNAs. The average molecular lengths are 1.1-1.2 kilobases, as
      determined by polyacrylamide gel electrophoresis and by electron microscopy.
      Products of messenger-dependent protein synthesis in vitro appear to be 1100 and
      2000 daltons heavier than the native polypeptides. Zein is like secretory
      proteins in having a precursor with an additional amino-terminal sequence.
      Although only one mRNA is seen in polyacrylamide gel electrophoresis, the
      combined size of the polypeptide products formed exceeds the coding capacity for
      one message of the size determined in this study. This suggests that there are at
      least two mRNAs of similar sizes for the zein polypeptides rather than one
      dicistronic message.

PMID- 16592497
TI  - Isolation of the in vivo emitter in bacterial bioluminescence.
AB  - A blue fluorescence protein has been isolated and purified from extracts of the
      luminous bacterium Photobacterium phosphoreum. It is a single polypeptide of
      molecular weight 22,000 with absorption maxima at 274 and 418 nm. It is
      efficiently fluorescent (varphi(F) 0.45), with a fully corrected spectral maximum
      (476 nm) and distribution identical to the in vivo bioluminescence from this same
      type of bacterium. At low concentration this fluorescence shifts towards the red
      and becomes identical to the in vitro bioluminescence emission. This spectral
      shift apparently results from a change in the protein pulled by dissociation of
      the chromophore (K(d) [unk] 10(-7) M). If the blue fluorescence protein is
      included in the in vitro bioluminescence reaction with reduced FMN, oxygen,
      aldehyde, and luciferase (P. phosphoreum), the bioluminescence spectrum is
      shifted towards the blue from its maximum at 490 nm to one at 476 nm, where it is
      again identical in all respects to the in vivo bioluminescence spectrum. This is
      accompanied by an increase in the initial light intensity by an order of
      magnitude at saturating levels of blue fluorescence protein, and the specific
      light yield of the luciferase is increased 4-fold. It is suggested that the blue
      fluorescence protein acts as a sensitizer of the bacterial bioluminescence
      reaction.

PMID- 16592498
TI  - Messenger RNA is conserved during drying of the drought-tolerant moss Tortula
      ruralis.
AB  - On rehydration after complete drying, the drought-tolerant moss Tortula ruralis
      (Hedw.) Gaertn., Meyer, and Scherb reforms its polyribosomes and can resume
      protein synthesis without new RNA synthesis. Results obtained with the double
      label ratio technique coupled with polyacrylamide disc gel electrophoresis show
      that (i) the proteins synthesized on rehydration are largely similar to those
      synthesized at the time of dehydration and (ii) inhibition of RNA synthesis does
      not alter the rate or the pattern of protein synthesis during rehydration of
      slowly dried moss. Poly(A)-rich RNA has been isolated from fresh and dried moss
      by chromatography on oligo(dT)-cellulose and has been translated in vitro in the
      cell-free wheat germ system. It is concluded that mRNA is conserved during
      complete drying of T. ruralis and supports protein synthesis on subsequent
      rehydration. This ability to conserve mRNA is a characteristic held in common by
      vegetative drought-tolerant tissue of T. ruralis and air-dried seeds of higher
      plants.

PMID- 16592499
TI  - Cytochemical studies on GERL, provacuoles, and vacuoles in root meristematic
      cells of Euphorbia.
AB  - The genesis of plant vacuoles has been studied by high-voltage and conventional
      electron microscopy. Vacuole genesis is a lysosomal multistep process: (i) GERL
      (Golgi-associated Endoplasmic Reticulum from which Lysosomes apparently form)
      produces provacuoles into which lysosomal enzymes and probably other materials
      appear to be concentrated and packaged; (ii) GERL-derived provacuoles cooperate
      to drive a programmed cellular autophagy leading to young vacuoles; and (iii) the
      young vacuoles swell and fuse together into a few large mature vacuoles which
      continue to collect the GERL-derived provacuoles throughout the life of the cell.

PMID- 16592500
TI  - RNA sequences complementary to citrus exocortis viroid in nucleic acid
      preparations from infected Gynura aurantiaca.
AB  - Molecular hybridization with (125)I-labeled citrus exocortis viroid RNA has been
      used to survey nucleic acid preparations from Gynura aurantiaca for viroid
      complementary molecules. A differential hybridization effect was detected between
      nucleic acid extracts from healthy and infected tissue in which significant RNase
      resistant (125)I-labeled citrus exocortis viroid resulted in hybridization
      studies with the infected tissue extracts. Subsequent characterization indicated
      that RNA from infected tissue was involved in the formation of a duplex molecule
      with citrus exocortis viroid RNA and had properties of an RNA.RNA hybrid.
      Subcellular fractionation of infected tissue indicates that the complementary RNA
      is present in nuclear and soluble RNA fractions. This RNA may represent an
      intermediate molecule in the replication of the viroid or a pathogenic expression
      and may have a regulatory role in the host cell.

PMID- 16592501
TI  - Lucibufagins: Defensive steroids from the fireflies Photinus ignitus and P.
      marginellus (Coleoptera: Lampyridae).
AB  - Feeding tests with thrushes (Hylocichla spp.) led to the isolation of three novel
      steroid pyrones from fireflies (Photinus ignitus and P. marginellus) responsible,
      in part at least, for the unpalatability of these insects to the birds. The term
      lucibufagin is coined for these steroidal pyrones. The closest known relatives of
      lucibufagins are the familiar cardiotonic bufadienolides, found in certain toads
      and plants.

PMID- 16592502
TI  - Potato spindle tuber and citrus exocortis viroids undergo no major sequence
      changes during replication in two different hosts.
AB  - Potato spindle tuber viroid and citrus exocortis viroid, each purified from
      tomato (Lycopersicon esculentum) and from Gynura aurantiaca, were iodinated in
      vitro with (125)I, digested with ribonuclease T1, and subjected to two
      dimensional RNA fingerprinting analysis. With the exception of minor variations,
      each viroid retained its distinctive fingerprint pattern irrespective of the host
      species from which it was isolated. We conclude that the nucleotide sequences of
      these viroids are principally determined by the infecting viroid and not by the
      host.

PMID- 16592503
TI  - Electrophilic and free radical nitration of benzene and toluene with various
      nitrating agents.
AB  - Electrophilic nitration of toluene and benzene was studied under various
      conditions with several nitrating systems. It was found that high orthopara
      regioselectivity is prevalent in all reactions and is independent of the
      reactivity of the nitrating agent. The methyl group of toluene is predominantly
      ortho-para directing under all reaction conditions. Steric factors are considered
      to be important but not the sole reason for the variation in the ortho/para
      ratio. The results reinforce our earlier views that, in electrophilic aromatic
      nitrations with reactive nitrating agents, substrate and positional selectivities
      are determined in two separate steps. The first step involves a pi-aromatic-NO(2)
      (+) ion complex or encounter pair, whereas the subsequent step is of arenium ion
      nature (separate for the ortho, meta, and para positions). The former determines
      substrate selectivity, whereas the latter determines regioselectivity. Thermal
      free radical nitration of benzene and toluene with tetranitromethane in sharp
      contrast gave nearly statistical product distributions.

PMID- 16592504
TI  - Intramolecular energy transfer in molecules with a large number of conformations.
AB  - The equations representing the decay kinetics of fluorescence of a donor
      luminophore in the presence of an acceptor in the same flexible molecule are
      discussed. The assumption that distances between luminophores attached to chain
      ends are not correlated with the relative orientations of luminophores is tested
      by theoretical calculations for the unperturbed chains Tyr-(Ala)(n)-Tyr with n
      equal to 4 and 9. It appears that for these chains, in which the conformation is
      dominated by entropic factors, the above assumption is satisfactory even for
      chains with a small number of repeating units (n = 4).

PMID- 16592505
TI  - Chemistry of low-valent molybdenum phosphite complexes: Models of seven
      coordinate reaction intermediates.
AB  - A simple synthesis of the zerovalent complex Mo[P(OCH(3))(3)](6) has been devised
      from a potassium reduction of MoCl(4)(tetrahydrofuran)(2) followed by reaction
      with trimethyl phosphite at 70 degrees . Protonation of this octahedral complex
      gave only low yields of the expected seven-coordinate hydride,
      HMo[P(OCH(3))(3)](6) (+). The major product was an octahedral nonhydridic cation,
      Mo[P(OCH(3))(3)](5)P(OCH(3))(2) (+), derived from proton cleavage of the P-O
      phosphite ester bond. This octahedral cation was stereochemically nonrigid,
      apparently through facile methoxy group migration. Close packing by methoxy
      groups in this fluxional cation was established through an x-ray crystallographic
      study of Mo[P(OCH(3))(3)](5)P(OCH(3))(2) (+)-PF(6) (-). Extended reaction of
      trifluoroactic acid with Mo[P(OCH(3))(3)](6) yielded the seven-coordinate
      hydride, HMo[P(OCH(3))(3)](4)(O(2)CCF(3)), which was near pentagonal bipyramidal
      and was stereochemically nonrigid.

PMID- 16592506
TI  - Differentiation in lacunary directions.
AB  - Let {theta(j)} be a lacunary sequence going to zero. Let [Formula: see text].
      Define [Formula: see text]. We prove [Formula: see text].

PMID- 16592507
TI  - On the algebraic construction and classification of Harish-Chandra modules.
AB  - Let G be a connected real semisimple Lie group. In this article a functor is
      defined which assigns to each irreducible finite dimensional representation of a
      Cartan subgroup of G a Harish-Chandra module for G. This functor is described by
      an explicit construction of modules and a sufficient condition is given for the
      image module to be irreducible. In the case when G is a linear group, this
      functor is used to exhibit all irreducible Harish-Chandra modules of G.

PMID- 16592508
TI  - Crystal structures of the alpha''-cerium phases.
AB  - Endo et al. [Endo, S., Sasaki, H. & Mitsui, T. (1972) J. Phys. Soc. Jpn. 42, 882
      885] have reported x-ray diffraction data for an unidentified phase of cerium
      metal observed in the 50- to 100-kbar range. It is shown that the unknown phase
      is a variant of the metastable monoclinic phase, alpha''-Ce, previously observed.
      The complete structure of the new form of alpha''-Ce is deduced.

PMID- 16592509
TI  - Limit theorems for weighted sums and stochastic approximation processes.
AB  - By establishing certain limit theorems for martingale transforms and weighted
      sums, a Marcinkiewicz-Zygmund strong law together with weak and strong invariance
      principles is developed for stochastic approximation processes, under minimal
      conditions on the errors.

PMID- 16592510
TI  - ATP-dependent Ca uptake into plant membrane vesicles.
AB  - Membrane vesicles were extracted from etiolated and light-grown plants, a plant
      cell suspension culture, and an alga. Upon addition of ATP and Mg(2+), active
      Ca(2+) uptake into the vesicles against a concentration gradient was shown. The
      dependence of this uptake on ATP and Mg(2+) concentrations, pH, and temperature
      is described. In the absence of oxalate, equilibrium between Ca(2+) uptake and
      efflux was reached after about 30 min. In the presence of oxalate, Ca(2+)
      accumulation continued for at least 120 min. Ca(2+) efflux from preloaded
      vesicles did not depend on ATP. Addition of the ionophores A23187 and Ro 20
      0006/006 caused an immediate release of accumulated free Ca(2+). ATP-dependent
      Ca(2+) uptake was not inhibited by 10 muM oligomycin.

PMID- 16592511
TI  - Inactivation and chemical alteration of mating factor alpha by cells and
      spheroplasts of yeast.
AB  - Mating factor alpha isolated from yeast culture filtrates was radiolabeled by
      lactoperoxidase-catalyzed iodination, with full retention of biological activity.
      The (125)I-labeled alpha factor bound at low levels to cells of both mating types
      (a and alpha) but not to spheroplasts. Despite the low level of binding, large
      quantities of alpha factor activity were lost by incubation with a cells and a
      spheroplasts, but not with alpha or a/alpha diploid cells. The amount of activity
      removed from the culture medium was much larger than the amount of (125)I-labeled
      alpha factor bound to the cells and was correlated with the appearance of
      radiolabeled derivatives separable by thin-layer chromatography. Upon removal of
      the cell wall of alpha and a/alpha cells, the spheroplasts acquired the ability
      to remove alpha factor activity from culture medium, to generate derivatives of
      alpha factor, and to respond to alpha factor by a morphological alteration
      resembling the response of a cells. These findings raise the possibility that the
      specific enzyme capable of altering alpha factor, possibly a peptidase, is
      associated with both a and alpha cells but is masked by the alpha cell wall. This
      suggestion is consistent with the observation that the alpha factor activities of
      G(1) arrest and cell elongation were blocked by preincubation of a cells with the
      protease inhibitor Trasylol.

PMID- 16592512
TI  - Symmetry and causality properties of physical fields.
AB  - Representations of groups of causality-preserving transformations on locally
      Minkowskian space-times, by actions on classes of wave functions of designated
      transformation properties, are analyzed, in extension of the conventional
      theoretical treatment of free relativistic particles. In particular, the
      constraints of positivity of the energy and finiteness of propagation velocity
      are developed, and the concept of mass is explored, within the indicated
      framework.

PMID- 16592513
TI  - Automorphic L-functions of half-integral weight.
AB  - We describe a theory of Whittaker models and L-functions for irreducible
      representations of a metaplectic covering group of GL(2). We explain how to use
      these L-functions to establish an arithmetical correspondence between "genuine"
      cuspidal representations of the metaplectic group and cuspidal representations of
      GL(2). When our ground field is Q, this correspondence generalizes and
      reformulates recent results of G. Shimura [(1973) Ann. Math. 97, 440-481]. A
      crucial role in our theory is played by what we call "exceptional" cusp forms
      those that are completely determined by just one Fourier coefficient.

PMID- 16592514
TI  - Clark's Theorem on linear programs holds for convex programs.
AB  - Given a linear minimization program, then there is an associated linear
      maximization program termed the dual. F. E. Clark proved the following theorem.
      "If the set of feasible points of one program is bounded, then the set of
      feasible points of the other program is unbounded." A convex program is the
      minimization of a convex function subject to the constraint that a number of
      other convex functions be nonpositive. As is well known, a dual maximization
      problem can be defined in terms of the Lagrange function. The dual objection
      function is the infimum of the Lagrange function. The feasible Lagrange
      multipliers are those satisfying: (i) the multipliers are nonnegative and (ii)
      the dual objective function is not negative infinity. It is found that Clark's
      Theorem applies unchanged to dual convex programs. Moreover, the programs have
      equal values.

PMID- 16592515
TI  - Nonequilibrium entropy, Lyapounov variables, and ergodic properties of classical
      systems.
AB  - We discuss the problem of defining (nonequilibrium) entropy in terms of the
      concepts of mechanics and of reconciling its monotonic increase with the
      Hamiltonian evolution of the dynamical system. This leads to investigating
      necessary and sufficient conditions for the existence of monotonically increasing
      quantities or the so-called Lyapounov variables of classical systems. It is found
      that the condition of "mixing" is necessary and the property of being K-flow is
      sufficient for the existence of a Lyapounov variable. The significance of the
      study of Lyapounov variables for the elucidation of the fundamental questions of
      statistical mechanics is briefly discussed. It is seen that every Lyapounov
      variable must fail to commute with at least some of the operators of
      multiplication by phase space functions. The uncertainty relations implied by
      this necessary noncommutativity would then set a limit on the simultaneous
      determination of entropy and trajectories in phase space. These considerations
      thus support and sharpen the view that the thermodynamical and the (microscopic)
      dynamical descriptions of classical systems could be consistently reconciled as
      being complementary descriptions analogous to the complementary descriptions
      encountered in quantum mechanics.

PMID- 16592516
TI  - On the derivation of linear irreversible thermodynamics for classical fluids.
AB  - We consider the microscopic derivation of the linearized hydrodynamic equations
      for an arbitrary simple fluid. Our discussion is based on the concept of
      hydrodynamical modes, and use is made of the ideas and methods of the theory of
      subdynamics. We also show that this analysis leads to the Gibbs relation for the
      entropy of the system.

PMID- 16592517
TI  - Brillouin light scattering measurement of the elastic properties of aligned
      multilamella lipid samples.
AB  - Brillouin measurements of the elastic properties are presented for aligned
      multilamella samples of both pure dipalmitoyl phosphatidylcholine at various
      temperatures and water concentrations and for the same compound containing 33
      mol% cholesterol at various temperatures and two water concentrations. For pure
      dipalmitoyl phosphatidylcholine the elastic moduli change significantly at the
      gel transition and the modulus for area compression of individual bilayers is
      inferred to be an order of magnitude larger below the gel transformation than
      above. The presence of cholesterol is shown to influence the elastic behavior of
      dipalmitoyl phosphatidylcholine.

PMID- 16592518
TI  - Photosynthetic characteristics and organization of chlorophyll in marine
      dinoflagellates.
AB  - The photosystem I reaction center complex, the P-700-chlorophyll a-protein, has
      been isolated from the photosynthetic membranes of two marine dinoflagellates,
      Gonyaulax polyedra and Glenodinium sp., by detergent solubilization with Triton X
      100. The complexes isolated from the two species were indistinguishable,
      exhibiting identical absorption properties (400-700 nm) at both room (300 K) and
      low (77 K) temperature. The room temperature, red wavelength maximum was at 675
      nm. The absorption properties, kinetics of photobleaching, sodium dodecyl sulfate
      electrophoretic mobilities, and chlorophyll a/P-700 ratio (50 +/- 10) of the P
      700-chlorophyll a-protein complexes from the two species also were essentially
      the same and similar to those properties characterizing P-700-chlorophyll a
      protein complexes of higher plants and green algae.Photosynthetic unit sizes were
      determined for cells grown at 1000 muW/cm(2). Both dinoflagellates had unit sizes
      (total chlorophyll/P-700 ratios) of about 600, even though the distribution of
      chlorophyll a, chlorophyll c, and peridinin in the light-harvesting components
      differed in Gonyaulax and Glenodinium. The number of photosynthetic units per
      cell in the two species correlates directly with their photosynthetic activities.
      A model is presented for the distribution of chlorophyll in the photosynthetic
      apparatus of these dinoflagellates which accounts for the known role of the
      isolated pigment-protein complexes and for the known photoadaptive physiology in
      pigmentation and photosynthesis for these species.

PMID- 16592519
TI  - Alternative mating strategies in the digger wasp Philanthus zebratus Cresson.
AB  - Males of at least six species of the digger wasp genus Philanthus are
      territorial, defending areas on the ground and evidently marking these with a
      pheromone. This is also true of P. zebratus at two widely separate localities in
      Colorado. However, males in an aggregation in Jackson Hole, Wyoming, are
      nonterritorial and participate in flights serving to intercept females leaving
      and entering the nesting area. The evidence suggests that this novel strategy may
      have arisen de novo as a result of unknown ecological and historical factors.

PMID- 16592520
TI  - Mathematical theory of group selection: Structure of group selection in founder
      populations determined from convexity of the extinction operator.
AB  - Genetic analysis for group selection is developed for the case of a biallelic
      locus (A, a) undergoing group selection of founder populations only. By contrast
      to R. Levins"E = E(x) models, extinction now depends on genetics at the propagule
      stage but acts uniformly on larger populations. Biological evidence supports this
      hypothesis, which also allows mathematical treatment at once simpler and
      biologically more general than the Fokker-Planck partial differential equation
      formalism adopted by Levins. It is presently possible to handle cytogenetics of
      both diploid and haplodiploid type. The model is set up as a quasideterministic
      recursion in the 5-simplex Sigma(5), collapsing both drift and mendelian
      selection effects into a single parameter u, which is a Fisher-Kimura-Ohta
      fixation probability. In the analysis, it is shown that the stability of the
      fixed points is determined by the convexity of the extinction operator acting on
      propagules, assumed to be of size 2.THUS, [FORMULA: see text] in which E(1) and
      E(3) are extinction probabilities for phenotypically uniform founder populations
      and E(2) is the corresponding probability for founder populations of mixed
      phenotype. Further parameter regions are defined where fixation of the group
      selected gene is globally stable, and this is still possible even when extinction
      pressure acting on carrying capacity populations becomes weak relative to a fixed
      mendelian selection strength.

PMID- 16592521
TI  - Mathematical aspects of divergent beam radiography.
AB  - At the present time, largely because of a breakthrough in radiology called
      computed tomography, the attenuation of x-ray beams is measured in extremely
      sensitive quantitative ways, and the information from many x-ray sources is
      assembled and analyzed on a computer. In this situation mathematics can make
      significant contributions concerning the nature of the information conveyed by x
      rays from many sources, the extent to which this information determines the
      object x-rayed, suitable configurations of sources, methods for using the data to
      build a detailed reconstruction of the object, etc. This article announces
      results on these topics for the divergent x-ray beam. The three-dimensionally
      divergent beam, or cone beam, presents new problems that do not appear in the two
      dimensional, or fan beam, case.

PMID- 16592522
TI  - Connectivity as an alternative to boundary integral equations: Construction of
      bases.
AB  - In previous papers Herrera developed a theory of connectivity that is applicable
      to the problem of connecting solutions defined in different regions, which occurs
      when solving partial differential equations and many problems of mechanics. In
      this paper we explain how complete connectivity conditions can be used to replace
      boundary integral equations in many situations. We show that completeness is
      satisfied not only in steady-state problems such as potential, reduced wave
      equation and static and quasi-static elasticity, but also in time-dependent
      problems such as heat and wave equations and dynamical elasticity. A method to
      obtain bases of connectivity conditions, which are independent of the regions
      considered, is also presented.

PMID- 16592523
TI  - Statistics of self-avoiding walks confined to strips and capillaries.
AB  - A long self-avoiding chain confined to a narrow strip or thin tube tends to be
      elongated in the direction of the strip or tube. The mean end-to-end separation
      of a long chain so confined becomes asymptotically proportional to the number of
      links in the chain as the contour chain length becomes infinite. By use of
      scaling arguments, it is shown that the mean end-to-end separation also becomes
      proportional to D(-1/3) for chains confined to two-dimensional strips and
      proportional to D(-2/3) for three-dimensional capillaries, where D is the width
      or diameter of the strip or capillary. These predictions have been verified by
      Monte Carlo studies of self-avoiding walks. The agreement is excellent for two
      dimensional systems, but less certain for those of three dimensions since less
      data are available for verification.

PMID- 16592524
TI  - Coherent stimulated light emission (lasing) in covalently linked chlorophyll
      dimers.
AB  - The covalently linked chlorophyll a dimer exhibits remarkably different
      properties in the folded and open configurations. In the folded configuration the
      absorption maximum is at 695 nm and the fluorescence maximum is at 730 nm. Laser
      output at 733 and 735 nm is obtained for solutions in wet benzene and 0.1 M
      ethanol/toluene, respectively. Measurements of fluorescence lineshapes, made with
      a transverse excited atmospheric (TEA) nitrogen laser for excitation, show the
      lifetime shortening associated with stimulated emission resulting from
      appreciable concentrations of molecules in S(1) excited states. In contrast, the
      open dimer has absorption and fluorescence spectra essentially the same as those
      of chlorophyll a monomer. Unlike either the folded dimer or chlorophyll a
      monomer, the open dimer shows no laser emission or fluorescene lifetime
      shortening. It does not appear that the behavior of the open dimer can be
      explained in terms of excimer or triplet formation or by nonradiative decay
      processes. It is suggested that absorption of the exciting radiation by S(1),
      leading to the formation of an exciplex or charge transfer state, may be
      involved. Significantly, no large changes in fluorescence quantum yield or
      fluorescence lifetime are observed for these dimers as compared to monomer
      chlorophyll. This suggests that concentration quenching and lifetime shortening
      in condensed chlorophyll systems involve more than the simple proximity of two
      chlorophyll molecules.

PMID- 16592525
TI  - Asymptotic representation of conformal maps of strip domains without boundary
      regularity.
AB  - Many parts of the subject of the boundary behavior of conformal mappings can be
      subsumed under the general heading of asymptotic representations of the Riemann
      mapping function near a boundary point. Asymptotic representations have, up to
      now, required that the boundary of the domain satisfy various types of regularity
      conditions. The results announced here give a method for obtaining asymptotic
      representations when the domain fails to satisfy such regularity conditions.

PMID- 16592526
TI  - The one-phase Stefan problem and the porous medium diffusion equation: Continuity
      of the solution in n space dimensions.
AB  - THE FOLLOWING PROBLEMS ARE CONSIDERED: (i) the one-phase Stefan problem, which
      describes the melting of ice, and (ii) the flow of gas in a porous medium. Both
      problems are considered in the n-dimensional space. The main result asserts that
      the solution [i.e., the temperature in problem (i) and the density in problem
      (ii)] is continuous.

PMID- 16592527
TI  - RNA-dependent RNA polymerase of tobacco plants.
AB  - Several properties of RNA polymerase (nucleosidetriphosphate:RNA
      nucleotidyltransferase, EC 2.7.7.6) active fractions obtained from tobacco
      plants, be they uninfected, infected with tobacco mosaic virus, or infected with
      tobacco necrosis virus, were compared. By the seven criteria tested, the RNA
      dependent RNA polymerase from these three sources behaved the same, although its
      activity is greatly but variably stimulated by the two virus infections. It thus
      appears probable that these two viruses do not code for this enzyme, but rely for
      their replication on their ability to stimulate production of a host enzyme. The
      conclusion that cells contain RNA replicating capability represents a
      modification of the central dogma of molecular biology.

PMID- 16592528
TI  - Photosynthetic unit size, carotenoids, and chlorophyll-protein composition of
      Prochloron sp., a prokaryotic green alga.
AB  - Six samples of the prokaryotic, unicellular algae Prochloron sp., which occur in
      association with didemnid ascidians, were collected from various localities in
      the tropical Pacific Ocean, and their pigments and chlorophyll-protein complexes
      were identified and characterized. No phycobilin pigments were detected in any of
      the species. Chlorophylls a and b were present in ratios of a/b = 4.4-6.9. The
      major carotenoids were beta-carotene (70%) and zeaxanthin (20%). Minor
      carotenoids of one isolate were identified as echinenone, cryptoxanthin,
      isocryptoxanthin, mutachrome, and trihydroxy-beta-carotene; no epsilon-ring
      carotenoids were found in any sample. Except for the absence of glycosidic
      carotenoids, the overall pigment composition is typical of cyanobacteria. A
      chlorophyll a/b-protein complex was present in Prochloron; it was
      electrophoretically and spectrally indistinguishable from the light-harvesting
      chlorophyll a/b-protein of higher plants and green algae. It accounted for 26%
      (compared to approximately 50% in green plants) of the total chlorophyll; 17% was
      associated with a P700-chlorophyll a-protein. The photosynthetic unit size of 240
      +/- 10 chlorophylls per P700 in Prochloron was about half that of eukaryotic
      green plants. A model is proposed for the in vivo organization of chlorophyll in
      Prochloron.

PMID- 16592529
TI  - Mutant strains of clover rhizobium (Rhizobium trifolii) that form nodules on
      soybean (Glycine max).
AB  - Mutant strains of Rhizobium trifolii that induce nitrogenase activity in the free
      living state were isolated. These strains, unlike the wild type, nodulated
      soybean and mungbean plants, producing effective nodules. One of the strains,
      strain DT72, also nodulated clover but the nodules were ineffective. Strain DT125
      consumed hydrogen gas from the gas phase, which can be coupled to nitrogenase
      activity under appropriate conditions.

PMID- 16592530
TI  - High accuracy finite difference approximation to solutions of elliptic partial
      differential equations.
AB  - A flexible finite difference method is described that gives approximate solutions
      of linear elliptic partial differential equations, Lu = G, subject to general
      linear boundary conditions. The method gives high-order accuracy. The values of
      the unknown approximation function U are determined at mesh points by solving a
      system of finite difference equations L(h)U = I(h)G. L(h)U is a linear
      combination of values of U at points of a standard stencil (9-point for two
      dimensional problems, 27-point for three-dimensional) and I(h)G is a linear
      combination of values of the given function G at mesh points as well as at other
      points. A local calculation is carried out to determine the coefficients of the
      operators L(h) and I(h) so that the approximation is exact on a specific linear
      space of functions. Having the coefficients of each difference equation, one
      solves the resulting system by standard techniques to obtain U at all interior
      mesh points. Special cases generalize the well-known 0(h(6)) approximation of
      smooth solutions of the Poisson equation to 0(h(6)) approximation for the
      variable coefficient equation -div(p grad[u]) + Fu = G. The method can be applied
      to other than elliptic problems.

PMID- 16592531
TI  - Joint probability distribution of the invariants comprising determinantal
      inequalities: Heuristic derivation.
AB  - Joint probability distributions are derived that are expressed in terms of the
      determinants that form the determinantal inequalities associated with the non
      negative Fourier series that represent crystal structures. The derivation
      involves heuristic considerations. It is therefore appropriate to test the
      distributions extensively by making comparisons with results obtained by other
      theoretical means and evaluations of the implications of the distributions. Those
      performed thus far on the low-order determinants (third and fourth orders) have
      provided satisfactory results. The determinantal probability distributions imply
      a general maximum determinant rule, contain a wealth of information, and provide
      numerous paths that may be followed for future development.

PMID- 16592532
TI  - Electric double layer dynamics by high-field electroluminescence in aqueous
      solution (Destriau effect).
AB  - Transient luminescence induced by high electric fields (>2.5 x 10(4) V/cm) was
      observed in aqueous solutions of 6,8-dihydroxypyrene-1,3-disulfonic acid. The
      light emission takes place both at the leading and the trailing edges of the
      perturbing electric square pulse. It occurs only during the variation of the
      applied field and disappears with a time constant of 0.5 musec at constant field.
      In solid state phosphors, where this phenomenon has been reported previously, it
      is known as the Destriau effect. The mechanisms of excitation and emission can be
      explained by the electron injection model, in which the time constant of the
      luminescence decay is associated with the rate of formation of the space charge.
      This space charge appears as a separation of positive and negative charges into a
      double layer stabilized by the applied potential.

PMID- 16592533
TI  - Photoprocesses in covalently linked pyrochlorophyllide dimer: Triplet state
      formation and opening and closing of hydroxylic linkages.
AB  - Covalently linked pyrochlorophyllide a dimers exist in solution in either
      "pinned" or unfolded form, depending on the concentration of hydroxylic (H
      bonding) or non-H-bonding Lewis bases. Laser flash photolysis studies have been
      made on these dimer forms and on pyrochlorophyllide monomer at 30-nsec
      resolution. Spectra and recovery kinetics, including observation of both the
      triplet decay and ground state folding reactions, show that the flash transient
      obtained from the pinned form consists of a triplet and ground state moiety in
      the unpinned configuration. A charge-transfer excited state is not seen.

PMID- 16592534
TI  - Incompressible minimal surfaces, three-dimensional manifolds with nonnegative
      scalar curvature, and the positive mass conjecture in general relativity.
AB  - We study three-dimensional Riemannian manifolds with nonnegative scalar
      curvature. We find new topological obstruction for such manifolds. Our method
      turns out to be useful in studying the positive mass conjecture in general
      relativity.

PMID- 16592535
TI  - General relativity, the Dirac equation, and higher symmetries.
AB  - An invariant derived from the curvature of a Sp(2) fiber bundle over a Riemannian
      manifold reduces to the Dirac Lagrangian for flat space-time.

PMID- 16592536
TI  - Dispersal in relation to carrying capacity.
AB  - Dispersal of the herbivorous vole Microtus pennsylvanicus from grassland to
      woodland was studied in an experimental field system during spring to autumn
      1969. Dispersal first occurred when there was at least 100 times more energy
      available than was required by the population. Sodium and phosphorus were in
      short supply in the food. By feeding selectively or copiously, voles could make
      up nutrient deficits and still consume only 10% of what was available. However,
      calculations show that depletion of the food was potentially severe in the
      forthcoming winter; consumption of energy- and nutrient-sufficient food had the
      potential of approaching 100%. These results suggest the following explanation of
      presaturation dispersal. Nutrients may be more limiting to herbivores than is
      total energy. Selective or copious harvesting becomes increasingly necessary as
      density increases. Natural selection, acting upon known genetic variation in
      dispersal propensity, has favored a dispersal response to environmental
      conditions that presage food shortage. Aggressive behavior and other forms of
      interactive behavior are the means by which land-tenured breeding individuals
      control their access to food resources and by which nontenured individuals are
      excluded and induced to disperse. Herbivore populations in general are limited
      well below carrying capacity. Carrying capacity may have been overestimated by
      ignoring chemical quality of the food, but the relationship is still probably
      true. The above explanation helps us to understand it. Because animals need to
      feed selectively, exploitation is based on cost-benefit balances and is less than
      total.

PMID- 16592537
TI  - Maxwell-type constructions for multiple nonequilibrium steady states.
AB  - A stochastic analysis is used to obtain Maxwell-type constructions for multiple
      nonequilibrium steady states in homogeneous systems. The stochastic theory shows
      that homogeneous molecular fluctuations can nucleate the Maxwell construction
      only on a time scale that is the order of a Poincare recurrence time and
      indicates that hysteresis should be observed. The nonrelevance of homogeneous
      fluctuations for systems that undergo phase separation or in which spatial
      structures occur is discussed.

PMID- 16592538
TI  - Local analytic hypoellipticity for square(b) on nondegenerate Cauchy-Riemann
      manifolds.
AB  - The local real analytic regularity of solutions to square(b), the complex
      boundary Laplacian, and related operators is proved for (p,q) forms on a
      nondegenerate, abstract, real analytic Cauchy-Riemann (C-R) manifold of dimension
      2n - 1 satisfying J. J. Kohn's condition Y(q). The problem is reduced to the
      study of general, "variable coefficient" operators, satisfying the same a priori
      estimates, on the Heisenberg group. L(2) methods only are used.

PMID- 16592539
TI  - Existence of a nonarithmetic lattice in SU(2,1).
AB  - The proof of the well-known conjecture that lattices in groups of R-rank greater
      than 1 are arithmetic has raised speculation about the existence of nonarithmetic
      lattices in the R-rank 1 group SU(n,1), n > 1. This paper presents an example of
      such a lattice Gamma(1). Gamma(1) consists of the intersection with SU(2,1) of a
      group Gamma generated by three complex reflections of order 5. The quotient
      SU(2,1)/Gamma(1) is compact.

PMID- 16592540
TI  - Strong consistency of least squares estimates in multiple regression.
AB  - The strong consistency of least squares estimates in multiple regression models
      with independent errors is obtained under minimal assumptions on the design and
      weak moment conditions on the errors.

PMID- 16592541
TI  - Maize plastid gene expressed during photoregulated development.
AB  - RNAs larger than about 6 S prepared from etioplasts of dark-grown maize
      seedlings, and from plastids at later stages of light-induced development, were
      labeled in vitro and hybridized to separated fragments of maize chloroplast DNA
      digested with endonucleases. The major nonribosomal RNA present in developing
      plastids, but virtually undetectable in etioplasts, hybridizes to chloroplast DNA
      Bam fragment 8 and has been mapped on the maize plastid chromosome. Other
      aliquots of RNA from plastids were translated in a rabbit reticulocyte-derived
      system. Developing plastids, and mature chloroplasts, but not etioplasts, contain
      mRNA for an approximately 34,500 dalton polypeptide. The simultaneous appearance,
      during light-induced maize plastid development, of RNA which hybridizes to Bam 8
      and is translated into a 34,500 dalton protein indicates that photoregulated
      expression of a single gene is being observed.

PMID- 16592542
TI  - Nucleotide sequence at the 5' extremity of turnip yellow mosaic virus genome RNA.
AB  - The sequence of the first 110 nucleotides at the 5' extremity of turnip yellow
      mosaic virus genome RNA has been determined. The sequence is blocked at its 5'
      terminus with the group pppm(7)G and contains two AUG triplets. The determined
      sequence bears a strong resemblance to the 5' noncoding region of rabbit beta
      globin mRNA. Region 95-103 of the sequence can base-pair with part of the 3'
      extremity of either the genome RNA or the coat protein mRNA.

PMID- 16592543
TI  - Messenger RNA for G1 protein of French bean seeds: Cell-free translation and
      product characterization.
AB  - The fraction of poly(A)-containing RNA isolated from ripening bean (Phaseolus
      vulgaris) cotyledons that sedimented at 16 S in linear logarithmic sucrose
      gradients was at least as active a messenger as viral RNA when added to a cell
      free protein-synthesizing system from wheat germ. The major products synthesized
      in vitro were polypeptides of about 47,000 and 43,000 daltons, corresponding to
      two of the three subunits of G1 protein, the most abundant bean seed storage
      protein. No trace of the largest (53,000 daltons) subunit was found among the
      polypeptides synthesized in vitro. Proof that the 47,000- and 43,000-dalton
      polypeptides coded by the 16S RNA were indeed subunits of G1 protein was obtained
      by immunoprecipitation with monovalent antibody to G1 protein and by
      electrophoretic mapping of peptides on acrylamide gels after digestion of
      mixtures of authentic protein and radioactive translation products with protease
      V8, chymotrypsin, and trypsin. The subunits synthesized in vitro were slightly
      smaller than the native subunits, probably because they lacked the sugar residues
      present on the holoprotein.

PMID- 16592544
TI  - Expression of hydrogenase activity in free-living Rhizobium japonicum.
AB  - A medium is described on which selected Rhizobium japonicum strains express
      hydrogenase (H(2) uptake) activity under free-living conditions. Low
      concentrations of carbon substrates, decreased oxygen tension, and the quantity
      of combined nitrogen in the medium were major factors influencing hydrogenase
      expression. Hydrogenase activity was dependent upon a preincubation period in the
      presence of H(2) under conditions such that the cells did not exhibit nitrogenase
      activity. H(2) uptake rates were easily measured amperometrically in aerobically
      or anaerobically prepared suspensions from free-living cultures. Six R. japonicum
      strains that formed nodules with the ability to utilize H(2) oxidized this gas
      when grown in free-living cultures. In comparison six randomly chosen strains
      forming nodules that lost H(2) in air either showed no or low capacity to take up
      H(2) under free-living conditions. The reduction of triphenyltetrazolium chloride
      in an agar medium was used to detect strains capable of oxidizing H(2). This
      method has enabled us to isolate a spontaneous R. japonicum mutant strain that
      has lost the ability to utilize H(2). This mutant strain forms nodules that
      evolve H(2) but other symbiotic characteristics appear normal. This strain will
      be useful in evaluating the importance of the hydrogenase system in the nitrogen
      fixing process of legumes.

PMID- 16592545
TI  - Ultrastructure and cytochemistry of Miocene angiosperm leaf tissues.
AB  - Angiosperm leaf fossils (16.7-25 x 10(6) years by potassium/argon dating)
      referable to Zelkova were isolated from pyroclastic deposits in the Succor Creek
      Formation, Oregon. These fossils reveal a three-dimensional structure in
      mesophyll cell layers and vascular bundles, while transmission electron
      microscopy of fixed tissues reveals well-preserved chloroplasts with grana stacks
      and starch, as well as nuclei with condensed chromatin. Transmission electron
      microscopy indicates that cell walls retain a cellulosic microfibrillar
      architecture, while ultrastructural and cytochemical confirmation is presented
      for chloroplast starch and the presence of native cellulose. The preservation of
      cell walls and cytologic structures in fossil materials of this age indicates an
      unusually mild fossilization process attending the post-depositional maturation
      of associated sediments. The preservation observed appears to be associated with
      rapid physical dehydration coupled with endogenous fixation by organic acids
      (possibly tannins and/or chlorophyll derivatives).

PMID- 16592546
TI  - Group selection on a quantitative character.
AB  - We derive a model of group and individual selection on a quantitative character
      that is similar to the single-locus "metapopulation" models of group selection.
      Two alternative methods for the colonization of new or vacant habitats are
      examined and their effects are contrasted. In one model, all populations
      contribute migrants to a common pool, the "migrant pool," from which colonists
      are drawn at random to fill vacant sites. In the migrant pool there is complete
      mixing of individuals from different populations. This model of colonization is
      the one used in all previous models of group selection. In the other model, the
      "propagule pool" model, each propagule is made up of individuals derived from a
      single population and there is no mixing of colonists from different populations
      during propagule formation. The analysis shows that much more between-population
      genetic variance can be maintained with the propagule pool model than with the
      migrant pool model. Consequently, group selection can be much more effective in
      natural populations than is commonly supposed.

PMID- 16592547
TI  - Quota methods for congressional apportionment are still non-unique.
AB  - Balinski and Young described a "quota method" for congressional apportionment and
      recommended it as "the only method satisfying three essential axioms" [Balinski,
      M. L. & Young, H. P. (1974) Proc. Natl. Acad. Sci. USA 71, 4602-4606]. This paper
      points out and repairs a slight defect in one of those axioms, producing a quota
      method slightly different from that described previously. It also presents an
      alternative to the "consistency" axiom of the paper and describes the "dual
      quota" method, uniquely satisfying the alternative axioms (which have exactly as
      much justification as the originals).

PMID- 16592548
TI  - Internal charge transfer in proteins to the Schiff bases of their lysine side
      chains.
AB  - Stereochemical investigations carried out with the aid of molecular models show
      that the Schiff bases formed between methylglyoxal and the primary amino groups
      of the lysine side chains of proteins can bend back in such a way to the N atoms
      of the peptide groups that a charge transfer can occur between these groups and
      the oxygen atoms of the Schiff bases. Ab initio molecular orbital calculations
      support this finding.

PMID- 16592549
TI  - Pompeiu's problem on discrete space.
AB  - Let [unk] be a finite family of finite subsets of the n-dimensional lattice Z(n),
      and let tau denote the group of all translations of Z(n). We shall here consider
      the Pompeiu problem for the family [unk]-namely, to determine when the only
      function f:Z(n) --> C such that [Formula: see text] is the zero function.

PMID- 16592550
TI  - Decomposition of the linking number of a closed ribbon: A problem from molecular
      biology.
AB  - A closed duplex DNA molecule relaxed and containing nucleosomes has a different
      linking number from the same molecule relaxed and without nucleosomes. What does
      this say about the structure of the nucleosome? A mathematical study of this
      question is made, representing the DNA molecule by a ribbon. It is shown that the
      linking number of a closed ribbon can be decomposed into the linking number of a
      reference ribbon plus a sum of locally determined "linking differences."

PMID- 16592551
TI  - The N-soliton solution of the Benjamin-Ono equation.
AB  - A theorem is deduced that reduces the problem of finding the N-soliton solution
      of the Benjamin-One equation to that of solving an algebraic equation of degree
      N.

PMID- 16592552
TI  - High yield photoreagents for protein crosslinking and affinity labeling.
AB  - 4-Nitrophenyl ethers are proposed as new high-yield photoreagents for protein
      crosslinking and affinity labeling. These are totally unreactive in the dark
      under biological conditions, but react quantitatively with amines at pH 8 upon
      irradiation with 366-nm light. The reaction of monoalkoxy-p-nitrobenzenes with an
      amine yields the corresponding free alcohol and substituted nitrophenylamine. In
      essence, the nitrophenyl group is transferred from the alcohol to the amine.
      Bifunctional affinity reagents of this type could be especially useful for
      placing the p-nitrophenyl chromophore adjacent to a binding site without blocking
      it. The corresponding 2-methoxy-4-nitrophenyl ethers react with amines by
      displacement of the methoxyl group. Thus, bifunctional reagents of this class
      could be photocrosslinkers. A maleimide-containing 2-methoxy-4-nitrophenyl ether
      was attached to human fetal hemoglobin at gamma-cysteine F9 stoichiometrically.
      Subsequent ultraviolet irradiation yielded a gamma-gamma crosslinked hemoglobin
      in 80% yield. The oxygenation properties of the derivative indicate that it is
      locked in a high affinity conformation and that all cooperativity is lost.

PMID- 16592553
TI  - Kinetic analysis of receptor-controlled tracer efflux from sealed membrane
      fragments.
AB  - A detailed kinetic analysis is presented for activator-receptor-mediated efflux
      of tracer substances from vesicular membrane systems in general and from sealed
      fragments of excitable membranes in particular. Rate constants and amplitudes, as
      the primary measurable quantities of the efflux kinetics, are expressed in terms
      of fundamental properties of vesicular membrane systems containing receptors of
      chemical gating systems. The experimental determination and theoretical analysis
      of single contributions to a complex receptor-controlled efflux has been treated
      for the acetylcholine receptor system; also the effect of "pharmacological
      densensitization" on efflux is explicitly formulated. The dependence of the
      measured efflux parameters on the concentration of activators can be used to
      derive the kinetic and thermodynamic constants for receptor activation and
      inactivation processes; a general kinetic scheme and two limiting cases are
      analyzed. The efflux of (22)Na from "excitable microsacs" of Torpedo marmorata is
      treated as an example, and the power of the rigorous analytical method is
      demonstrated. In particular, the analysis of efflux amplitudes from only a few
      data points offers an alternative to the longer lasting measurements for
      obtaining efflux curves when a safety factor is involved, as in the case of
      tracer ions like (22)Na.

PMID- 16592554
TI  - Variation in mitochondrial translation products associated with male-sterile
      cytoplasms in maize.
AB  - Mitochondria were isolated under sterile conditions from maize lines with normal
      cytoplasm and with T, C, and S sources of cytoplasmic male sterility. Protein
      synthesis by these mitochondria was dependent upon the presence of ADP and an
      oxidizable substrate or an energy generating system and displayed characteristic
      sensitivity towards inhibitors of protein synthesis. Approximately 20
      polypeptides were detected by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis of the [(35)S]methionine-labeled mitochondrial translation
      products. Mitochondria from the T and C cytoplasms were characterized by the
      synthesis of a single additional or variant polypeptide.These observations are
      discussed with reference to the possible mechanisms of male sterility and the
      susceptibility of plants with T cytoplasm to Helminthosporium maydis, race T. Our
      results also suggest a potentially rapid method of classifying sources of
      cytoplasmic male sterility that could be used in conjunction with existing
      methods, which depend on patterns of fertility restoration after an extended
      breeding program.

PMID- 16592555
TI  - Determination of lipid A and endotoxin in serum by mass spectroscopy.
AB  - A quantitative technique for determining lipid A content of endotoxin added to
      serum by combined gas chromatography-mass spectrometry is described. This
      technique uses detection of the beta-hydroxymyristic acid content of Salmonella
      minnesota R595 lipopolysaccharide by selected ion monitoring at atomic mass unit
      of 315.4 The fatty acids produced on hydrolysis of serum containing
      lipopolysaccharide were extracted and the methyl esters were made. Silica gel
      chromatography was used to separate methyl esters of hydroxy fatty acids from
      other fatty acid methyl esters. Trimethylsilyl ether derivatives of the hydroxy
      fatty acid methyl ester fraction were quantitated by this technique. As little as
      200 fmol of beta-hydroxymyristic acid could be detected.

PMID- 16592556
TI  - Steering responses of flying crickets to sound and ultrasound: Mate attraction
      and predator avoidance.
AB  - We investigated the steering responses of tethered, flying adult female crickets
      (Teleogryllus oceanicus) to acoustic stimulation. Crickets responded
      directionally to directional sound stimulation by bending their abdomens and hind
      legs to one side. We interpret this response as an attempt to turn. When
      stimulated with a model of conspecific calling song with a carrier frequency of
      from 3 to 9 kHz, crickets turned toward the sound source. We believe that this
      indicates a positive phonotactic response of flying females to calling,
      conspecific males. When offered a choice between conspecific song and the song of
      another species, females turned exclusively toward conspecific song,
      demonstrating that the response is species specific. The direction of the
      response is dependent on the carrier frequency of the song, and it demonstrates
      frequency discrimination. Females turned toward calling song when it was played
      at carrier frequencies from 3 to 9 kHz, but they turned away from the same song
      pattern played at carrier frequencies from 30 to 70 kHz. This negative phonotaxis
      to ultrasonic stimuli suggests that crickets, like some other nocturnal flying
      insects, can evade bats by acoustic detection.

PMID- 16592557
TI  - Characterization of the blue copper site in oxidized azurin by extended x-ray
      absorption fine structure: Determination of a short Cu-S distance.
AB  - The primary coordination environment of the "blue" copper ion in oxidized azurin
      has been elucidated by x-ray absorption spectroscopy. The most striking feature
      is the unambiguous presence of a very short copper-sulfur distance at 2.10 +/-
      0.02 A. Nitrogen ligands, presumed to be from imidazoles, are found at 1.97 A.
      There is some evidence that the copper coordination sphere may be completed by a
      second sulfur, the distance of which is determined with much less certainty.

PMID- 16592558
TI  - Phospholipid synthesis: Oxazaphospholanes and dioxaphospholanes as intermediates.
AB  - The synthesis of phospholipids described herein allows an almost quantitative
      conversion of 1,2-diacylglycerols to phospholipids via cyclic intermediates such
      as oxazaphospholanes or dioxaphospholanes, which are the only products observed
      when ethanolamine or ethylene glycol is allowed to react with phosphatidic acid
      dichlorides. The acidic hydrolysis of the cyclic intermediates occurs rapidly
      without the formation of by-products and results in phospholipids differing in
      the structure of the polar part depending on which vicinal aminoalcohols or diols
      are used. For instance, phosphatidylethanolamines, -(N-methyl)ethanolamines, and 
      serine benzyl esters are directly formed from the corresponding
      oxazaphospholanes. Phosphatidyl(N,N-dimethyl)ethanolamines and -cholines are
      prepared by amination of the bromoethyl esters of phosphatidic acids, which can
      be obtained by treatment of dioxaphospholanes with sodium bromide. A similar
      sequence of reactions starting from 1-acyl-2-benzylglycerols or monoacylpropane
      1,3-diols will result in the respective monoacyl analogues such as
      lysophospholipids or the so-called desoxylysophospholipids. The mild reaction
      conditions, good yields (>90% based on diacylglycerol), and high purity of the
      products make this route an attractive procedure for phospholipid synthesis; in
      addition, it avoids the need for chromatography and thus can be utilized on a
      large scale.

PMID- 16592559
TI  - One class of meromorphic solutions of general two-dimensional nonlinear
      equations, connected with the algebraic inverse scattering method.
AB  - For systems of nonlinear equations having the form [L(n) - ( partial
      differential/ partial differentialt), L(m) - ( partial differential/ partial
      differentialy)] = 0 the class of meromorphic solutions obtained from the linear
      equations [Formula: see text] is presented.

PMID- 16592560
TI  - Stability of local rings of dimension 2.
AB  - The notion of stability of a local ring arises naturally in investigating
      completed moduli spaces via geometric invariant theory. A scheme corresponding to
      a boundary point of a moduli space of nonsingular varieties cannot have unstable
      singular points. This paper reports some results concerning the stability of
      surface singularities. If a two-dimensional Cohen-Macaulay local ring R is
      semistable, its multiplicity must be less than seven and either equal to or 1
      less than its embedding dimension. If the multiplicity of R is equal to its
      embedding dimension, the singularity of R must be a simple or cyclic elliptic
      singularity or the nonnormal limit of such a singularity. The results for the
      case when the multiplicity of R is less than its embedding dimension are still
      incomplete; the possible singularities that may arise when the multiplicity of R
      is equal to 2 or 3 are described.

PMID- 16592561
TI  - Spectroscopic sensitivity of linear-benzoadenine nucleotides to divalent metal
      counterions, side chain conformations, micelles, and enzymes.
AB  - From pK(a) data for lin-benzoadenosine 5'-mono-, 5'-di-, and 5'-triphosphates,
      which are fluorescent "stretched-out" analogues of adenine nucleotides, it was
      possible to designate the cases of interaction of phosphate with the
      heteroaromatic moiety. The addition of divalent metal cations or quaternary
      ammonium micelles diminishes the direct intramolecular interaction between the
      phosphate(s) and base and consequently brings the pK(a) values close to that of
      lin-benzoadenosine. Fluorescence spectroscopy was used to investigate the
      interaction of lin-benzoadenine nucleotides with Mg(2+), Mn(2+), and Co(2+). The
      association constants for the formation of such complexes were obtained from
      measurements of steady-state fluorescence quenching. Phase and modulation
      measurements of the fluorescence lifetimes of lin-benzoadenine nucleotides as a
      function of Co(2+) concentration permitted determination of the static component
      of the quenching due to intramolecular complex formation. The association
      constants of the lin-benzoadenine nucleotides with all of the divalent metal ions
      studied were greater than those observed for the corresponding adenine
      nucleotides and were in the order: lin-benzo-ATP > lin-benzo-ADP > lin-benzo-AMP.
      Fourier transform (1)H NMR of lin-benzo-ATP in the presence of Co(2+) showed
      broadening of the aromatic proton signals, the 2-H signal (corresponding to the 8
      H in ATP) being the most affected. Models are proposed to explain the phosphate
      base interaction, the influence of metal ions on base protonation, and the
      intramo- the intramolecular quenching observed in the complexes due to
      paramagnetic ion (Co(2+), Mn(2+)) and base interaction.

PMID- 16592562
TI  - Arsoniumphospholipid in algae.
AB  - A novel phospholipid containing arsenic was formed by all marine algae cultured
      in [(74)As]arsenate. Components of the labeled algal extracts readily separated
      by two-dimensional paper radiochromatography. Base-catalyzed deacylation of the
      major lipid yielded a phosphodiester identical to one of the two major water
      soluble compounds. Acid or enzymic hydrolysis of the phosphodiester produced a
      product identified as trimethylarsoniumalactic acid. The structure of the
      phospholipid therefore is O-phosphatidyltrimethylarsoniumlactic acid.
      Detoxication of arsenate by marine algae leads to accumulation of the
      arsoniumphospholipid as a major reservoir for arsenic. Its degradation to
      trimethylarsoniumbetaine, dimethylarsinic acid, methanearsonic acid, and arsenate
      in marine food chains and its metabolism in human beings are of considerable
      interest.

PMID- 16592563
TI  - Rhynchosporoside, a host-selective toxin produced by Rhynchosporium secalis, the
      causal agent of scald disease of barley.
AB  - Rhynchosporoside, a phytotoxic compound, has been isolated from cultures of
      Rhynchosporium secalis, the causal agent of scald disease of barley. The toxin is
      a cello-bioside of 1,2-propanediol. The compound may play some role in symptom
      expression because it was isolated from diseased plants in concentrations similar
      to those that could cause symptoms in toxin-treated plants. The toxin causes leaf
      tip and marginal necrosis and subsequent chlorosis of the entire leaf. The toxin
      affects only certain cultivars and lines of barley and rye; however, it also
      affects certain nonhosts of R. secalis. The genetic factor controlling host
      resistance to the fungus is not identical to that controlling insensitivity to
      the toxin.

PMID- 16592564
TI  - Social dynamics and the quantifying of social forces.
AB  - SOCIAL AND INDUSTRIAL EVOLUTIONARY PROCESSES ARE CONSIDERED TO BE A SEQUENCE OF
      REPLACEMENTS OR SUBSTITUTIONS: new ideas for old, new labor patterns for old, new
      technologies for old. The logistic equation has often been used to describe
      population growth processes and replacement processes. It sometimes suffers from
      contradicting observational data. It is shown here that the deviations are often
      associated with unusual intermittent events-wars, strikes, economic panics, etc.
      and that in many cases a few years after the event it can be abstracted as an
      instantaneous delta function impulse. After the event, the evolutionary process
      continues along its normal course. A formula is derived to use the observational
      data to determine the strength of the impulse modeling an event.

PMID- 16592565
TI  - General properties of the Yang-Mills equations in physical space.
AB  - With the formulation of the gauge group as a Banach-Lie group of suitable Sobolev
      type, the Cauchy problem for the Yang-Mills equation in physical space-time
      reduces rigorously to the case of the temporal gauge. In this gauge there exist
      spatially global strong solutions for given data for field and potential that are
      L(2) together with one or two derivatives (respectively). Regarding global
      existence in time, there is strong unicity, strong existence unless the potential
      becomes unbounded, and existence of a quasi-solution for arbitrary finite-energy
      Cauchy data. The variety of solutions of the equations is endowed with a
      canonical symplectic structure. This structure is degenerate to an extent
      precisely reflecting gauge-invariance and is conformally invariant.

PMID- 16592566
TI  - Kinematics of faint white dwarfs.
AB  - An analysis has been made for solar motion for 128 very faint white dwarfs of
      color class b or a. While about 40% of these stars may be high-velocity objects,
      it seems definitely indicated that the luminosity of all of them is considerably
      lower than that for the "normal" white dwarf of the same color.

PMID- 16592567
TI  - Experimental evidence for secondary protein-chromophore interactions at the
      Schiff base linkage in bacteriorhodopsin: Molecular mechanism for proton pumping.
AB  - Resonance Raman spectroscopy of the retinylidene chromophore in various
      isotopically labeled membrane environments together with spectra of isotopically
      labeled model compounds demonstrates that a secondary protein interaction is
      present at the protonated Schiff base linkage in bacteriorhodopsin. The data
      indicate that although the interaction is present in all protonated
      bacteriorhodopsin species it is absent in unprotonated intermediates.
      Furthermore, kinetic resonance Raman spectroscopy has been used to monitor the
      dynamics of Schiff base deprotonation as a function of pH. All our results are
      consistent with lysine as the interacting group. A structure for the interaction
      is proposed in which the interacting protein group in an unprotonated
      configuration is complexed through the Schiff base proton to the Schiff base
      nitrogen. These data suggest a molecular mechanism for proton pumping and ion
      gate molecular regulation. In this mechanism, light causes electron
      redistribution in the retinylidene chromophore, which results in the
      deprotonation of an amino acid side chain with pK >10.2 +/- 0.3 (e.g., arginine).
      This induces subsequent retinal and protein conformational transitions which
      eventually lower the pK of the Schiff base complex from >12 before light
      absorption to 10.2 +/- 0.3 in microseconds after photon absorption. Finally, in
      this low pK state the complex can reprotonate the proton-deficient high pK group
      generated by light, and the complex is then reprotonated from the opposite side
      of the membrane.

PMID- 16592568
TI  - Protected homo-oligopeptide structure: Model for preferred conformation of a
      linear methionine heptapeptide in chloroform.
AB  - The (1)H nuclear magnetic resonance spectra for a protected linear heptapeptide
      of methionine, Boc-Met(7)-OMe, were measured in dimethyl-d(6) sulfoxide and
      C(2)HCl(3) solutions. In the former, the peptide is disordered. In C(2)HCl(3),
      preferred (short-range) interactions exist that dominate the overall secondary
      structure of the peptide. A model is proposed in which seven-membered ring
      structures are initiated at the NH(2)-terminus and propagate toward the carboxyl
      terminus. The first seven-membered ring contains a strong hydrogen bond between
      the amide NH of residue 2 and the carbonyl oxygen atom of the urethane blocking
      group. As one proceeds toward the carboxyl terminus the hydrogen bond strength of
      succeeding rings decreases, and at residue 5 the peptide chain assumes an
      extended structure that is stabilized by intermolecular hydrogen bonds. The model
      accounts for most of the results from (1)H NMR and infrared studies on the
      heptapeptide and is consistent with conformational energy calculations on homo
      oligopeptides. It suggests that the COOH-terminal residues may serve as the
      nucleus for intermolecular peptide-peptide associations.

PMID- 16592569
TI  - Nonexponential fluorescence decay of aqueous tryptophan and two related peptides
      by picosecond spectroscopy.
AB  - Time-resolved fluorescence spectroscopy of tryptophan and two related dipeptides,
      tryptophylalanine and alanyltryptophan, has been carried out on the subnanosecond
      time scale by using picosecond exciting pulses at a wavelength of 264 nm.
      Detection was with an ultrafast streak camera coupled to an optical multichannel
      analyzer. The zwitterions of these molecules show a definite nonexponential
      fluorescence decay which can be analyzed in terms of two exponentials. The two
      decay rates increase strongly with increasing temperature, as does the weight of
      the faster component. In tryptophan at pH 11, where the amino group is
      deprotonated, there remains only a single temperature-dependent exponential. The
      results are interpreted in terms of two kinds of trapped conformers in the
      excited state that interconvert no quicker than the time scale of the
      fluorescence. A model is suggested in which the nonradiative processes in one
      conformer approximate those in the bare indole moiety. The nonradiative decay
      rate of the other conformer is substantially faster. It is believed that the
      process responsible for this fast decay is intramolecular electron transfer from
      the indole to the amino acid side chain. The predilection for this electron
      transfer depends on steric relationships as well as on the electron-attracting
      power of the carbonyl group. This picture is consistent with earlier fluorescence
      quantum yield results. In fact, a self-consistent picture emerges from the
      temporal and yield data that quantitatively explains most important facets of
      tryptophan photochemistry in aqueous solution.

PMID- 16592570
TI  - Deuterium nuclear magnetic resonance investigation of the effects of proteins and
      polypeptides on hydrocarbon chain order in model membrane systems.
AB  - Deuterium Fourier-transform nuclear magnetic resonance spectra have been obtained
      of 1-myristoyl 2-(14,14,14-trideutero)myristoyl phosphatidylcholine bilayers at
      34.1 MHz by using the quadrupole echo pulse technique. Thereby, we have
      investigated the effects upon the deuterated dimyristoyl phosphatidylcholine
      bilayers of the following proteins and polypeptides: gramicidin A, bacteriophage
      f1 coat protein, beef brain myelin proteolipid apoprotein, cytochrome b(5), and
      cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). Above
      T(c), the transition temperature between the gel and liquid crystal phases, the
      quadrupole splitting of the deuterium-labeled methyl group is reduced or
      collapsed in the presence of protein or polypeptide. No evidence has been found
      for ordered "boundary lipid." Below T(c), the spectra show that the hydrocarbon
      chains are prevented from crystallizing by the protein (or polypeptide)
      incorporated in the membrane. Similar disordering effects above T(c) are also
      seen when an unsaturated lipid, 1-(16,16,16-trideutero)palmitoyl 2-palmitoleyl
      phosphatidylcholine is complexed with cytochrome oxidase.

PMID- 16592571
TI  - A photochemical technique for measuring lateral diffusion of spin-labeled
      phospholipids in membranes.
AB  - A technique is described for the measurement of lateral diffusion of any spin
      labeled molecule in planar phospholipid multilayers, using low probe
      concentrations and a photochemical reaction to generate the initial concentration
      gradient. Features of the technique include simplicity of data analysis,
      versatility, and applicability over a wide range of motional rates. Measurements
      have been made on dimyristoyl phosphatidylcholine and dipalmitoyl
      phosphatidylcholine in the fluid phase (using a phospholipid with head-group spin
      label), and excellent agreement is found with recent nuclear magnetic resonance
      spin-echo measurements, as well as with other spin-label and fluorescence
      photobleaching results.

PMID- 16592572
TI  - Hysteresis effects of CH(4) and CH(4) in the regions of the solid-phase
      transitions.
AB  - The thermodynamic model of hysteresis in phase transitions based on the regular
      solution theory, previously developed, was applied to the solid phases of
      C(1)H(4) and C(2)H(4). The width and height of the hysteresis loops for these
      systems were calculated and compared with the experimental data; agreement was
      satisfactory.

PMID- 16592573
TI  - Second Leray spectral sequence of relative hypercohomology.
AB  - A second Leray spectral sequence of relative hypercohomology is constructed.
      (This is skew in generality to an earlier one constructed by S. Lubkin [(1968)
      Ann. Math. 87, 105-255].) The Mayer-Vietoris sequence of relative hypercohomology
      [Lubkin, S. (1968) Ann. Math. 87, 105-255] is also generalized.

PMID- 16592574
TI  - Inversion problem for singular integral operators: C-approach.
AB  - The inversion problem is solved for a wide class of singular integral operators,
      in particular for Wiener-Hopf operators in several variables, Mihlin-Calderon
      Zygmund operators on bounded domains, and Folland-Stein operators on compact
      nondegenerate Cauchy-Riemann manifolds.

PMID- 16592575
TI  - The dimension of product spaces.
AB  - The covering dimension of a product space can exceed the sum of the dimensions of
      its factors. A separable metric space X and a paracompact space Y are constructed
      such that dim X + dim Y = 0 < 1 = dim(X x Y). Related results are also discussed.

PMID- 16592576
TI  - On positivity of pseudo-differential operators.
AB  - In this paper we obtain new lower bounds for pseudo-differential operators with
      non-negative symbols, thus providing a sharper form of Garding's inequality.

PMID- 16592577
TI  - Light regulation of specific mRNA species in Lemna gibba L. G-3.
AB  - Polyadenylated RNA was isolated from Lemna gibba L. G-3 and translated in a cell
      free system from wheat germ. When plants were placed into complete darkness for 4
      days, then returned to light for 18 hr, increased amounts of polyadenylated mRNA
      for at least two polypeptides were detected by in vitro translation over those
      amounts present in the dark. These two polypeptides have molecular weights of
      32,000 and 20,000. The 20,000 dalton polypeptide was identified by
      immunoprecipitation as the precursor to the small subunit of the photosynthetic
      enzyme ribulose-1,5-bisphosphate carboxylase [3-phospho-D-glycerate carboxy-lyase
      (dimerizing), EC 4.1.1.39]. The polyadenylated mRNA that codes for the small
      subunit is not detectable by immunoprecipitation of translation products in the
      dark-treated tissue. Plants growing in the light actively synthesize both
      subunits of ribulose-1,5-bisphosphate carboxylase, but synthesis of these
      proteins was found to be greatly diminished in plants placed in darkness for 4
      days. These results indicate that white light can dramatically affect the steady
      state levels of specific polyadenylated mRNAs.

PMID- 16592578
TI  - Room-temperature magnetic properties of oxy- and carbonmonoxyhemoglobin.
AB  - The magnetic susceptibility and the density of human oxy-(HbO(2)) and
      carbonmonoxyhemoglobin (HbCO) solutions of various concentrations have been
      measured at room temperature, with pure water used as a calibrant. Solutions of
      unstripped and stripped HbO(2) at pH 7.2 in unbuffered water solvent were always
      found to be less diamagnetic than pure water, whereas solutions of HbCO in
      identical conditions were always found to be more diamagnetic than pure water.
      After correcting for concentration-dependent density changes and assuming the
      HbCO samples to be fully diamagnetic, the paramagnetic reduction of the
      diamagnetic susceptibility of HbO(2) corresponds to a molar susceptibility per
      heme (chi(M) (heme)) of 2460 +/- 600 x 10(-6) cgs/mol.

PMID- 16592579
TI  - Bacteriochlorophyll electronic transition moment directions in
      bacteriochlorophyll a-protein.
AB  - The low-temperature 800-nm band absorption and circular dichroism spectra of the
      bacteriochlorophyll (Bchl) a-protein from Prosthecochloris aestuarii strain 2K
      are analyzed theoretically. These spectra show considerable structure that is
      attributed primarily to resonance (exciton) interactions among the lowest singlet
      transitions of the Bchl a molecules contained in each protein. We calculate these
      spectra from the known arrangement of the Bchl molecules in the protein. With the
      conventional assignment of the lowest singlet transition of Bchl a as Q(y) (y
      polarized), agreement of calculated spectra with experiment is poor. All of our
      attempts, based on this conventional assignment, to improve the theoretical fits
      to absorption and circular dichroism spectra simultaneously are unsuccessful.
      However, by making the simple but unconventional assumption that the lowest
      singlet transition in each of the Bchl a molecules in each protein is x-polarized
      rather than y-polarized, we find good agreement between calculated and observed
      spectra. If these results are not fortuitous, they indicate that there is a
      systematic error in the protein structural model, that the conventional
      assignments of Bchl a transitions are incorrect, or that the protein environment
      provides a sufficiently strong perturbation to rotate the lowest singlet
      transition moment direction by approximately 90 degrees , presumably by changing
      the order of certain of the Bchl a orbitals.

PMID- 16592580
TI  - Reaction to phytotoxins in a potato population derived from mesophyll
      protoplasts.
AB  - Alternaria solani, the causal agent of early blight disease in potato, produces
      two host-specific, lipidlike toxins in culture. Both compounds are required in
      the leaf bioassay for the elicitation of typical early blight symptoms, but the
      compounds are individually inactive. The procedures for the preparation of both
      compounds are outlined. These compounds can be used effectively to select for
      toxin-insensitive and sensitive clones of a Russet Burbank potato cultivar that
      have been regenerated from single mesophyll protoplasts. Furthermore, both
      sensitivity and insensitivity to the toxins in these clones is well correlated
      with susceptibility and resistance to A. solani. Potato clones that have been
      produced by somatic cell regeneration techniques maintain their reaction type to
      these fungal toxins for at least two generations of vegetative propagation. The
      genetic basis for this variation among these potato clones remains to be
      explained.

PMID- 16592581
TI  - Does environmental variability limit niche overlap?
AB  - A stochastic theory of limiting similarity is presented that attempts to quantify
      the relationship between tolerable niche overlap among competing species and the
      degree of environmental fluctuation. The theory is based on a heuristic
      analytical approximation that provides conditions under which a rare invading
      species can increase in the presence of a community of established competitors.
      The major qualitative conclusion, derived from investigating two symmetric,
      discrete-time, stochastic analogs of the Lotka-Volterra competition equations, is
      that weak to moderate stochastic variation does not appear to limit significantly
      the similarity of competing species. This result is in sharp contrast to the
      conclusions of May and MacArthur's pioneering study of stochastic limiting
      similarity. A possible reason for this discrepancy is explored.

PMID- 16592582
TI  - Estimation of expected number of rare alleles of a locus and calculation of
      mutation rate.
AB  - An approach is described for the estimation of the number of rare variants in the
      population from the number in a sample drawn at random from the population. This
      quantity is used to derive an estimate of the mutation rate. The data required
      are the number of rare variants in the sample and the distribution of offspring
      within a population of well-defined size with little or no immigration.
      Application of this approach to data on 28 loci assayed in the Yanamamo, a tribe
      of South American Indians, yields an average mutation rate of 0.1 approximately
      0.2 x 10(-5). Determination of this figure is subject to several assumptions
      concerning the nature of the rare variants and the structure of the population.
      Violation of these assumptions will generally result in the underestimate of the
      true mutation rate.

PMID- 16592583
TI  - Direct selection in vitro for herbicide-resistant mutants of Nicotiana tabacum.
AB  - Seven cell lines of Nicotiana tabacum resistant to the herbicide picloram were
      isolated from cell cultures. In crosses of plants regenerated from four cell
      lines, resistance was inherited as a single dominant Mendelian allele. Plants
      could not be regenerated from one cell line, and expression of resistance proved
      unstable in two others.

PMID- 16592584
TI  - Sequence variability of immunoglobulins considered from the standpoint of
      population genetics.
AB  - The probability of gene identity between members of a multigene family was
      investigated, assuming mutation, random genetic drift, and unequal crossing-over.
      The theoretical results on the equilibrium and transient behavior of the identity
      probability were applied to the analyses of sequence variability in the variable
      regions of immunoglobulins. The probability of amino acid identity between
      corresponding residue sites at different but homologous immunoglobulin sequences
      was computed both within and between species from data reported by other workers.
      The average probability of amino acid identity was obtained for the hypervariable
      regions and also for the framework regions. From statistical analyses based on
      population genetics theory it is concluded that somatic mutations cannot be the
      major cause of hypervariability and that the results can readily be explained by
      the germ line theory.

PMID- 16592585
TI  - Colored lattices.
AB  - Combinations of translations and color permutations are derived that leave a
      periodic array of colored points-a colored lattice-apparently unchanged. It is
      found that there are three types of colored lattices: (1) those in which all rows
      and nets have more than one color, (2) those in which there are rows with only
      one color, and (3) those in which there are both rows and nets with only one
      color. The color permutation groups of colored lattices are all Abelian. The
      direct product of three independent cyclic subgroups is required by type 1, but
      only two are required by type 2; in type 3 the color permutation group consists
      of the n powers of a cyclic permutation of all n colors present-i.e., the group
      consists of a single cycle.

PMID- 16592586
TI  - Some new singular Fourier-Stieltjes series.
AB  - Singular continuous probability measures on the circle group are constructed
      whose Fourier-Stieltjes transforms converge to zero very rapidly and also have
      positive partial sums. Partial results for the line and for arbitary compact
      infinite Abelian groups are also obtained.

PMID- 16592587
TI  - Locality principle in wave mechanics.
AB  - This paper proves a locality principle for a wave-mechanical particle governed by
      the Schrodinger equation. It is shown that rho(r,beta), the Laplace transform of
      the local density of states n(r,E), depends significantly only on the potential
      V(r') at points r' near r. The effect of changes of V(r') at distant points r'
      (|x(i)' - x(i)| > a) on rho(r,beta) decay in a Gaussian fashion with a. This
      result sheds some light on the locality of physical properties of extended
      systems and provides general support for various local methods of calculation.

PMID- 16592588
TI  - K-resistant mutants and "adaptation" in Paramecium.
AB  - A class of mutants of Paramecium tetraurelia has been isolated by adding a
      critical amount of K(+) to mutagenized, autogamized cultures. Adding 35 mM K(+)
      to the medium kills the wild type. The mutants can grow at 35 mM K(+) and some
      survive an addition of up to 80 mM K(+). Thirty-three lines of such mutants have
      been studied. These mutants have few or no behavioral abnormalities in culture
      medium.Paramecia can "adapt." Hildebrand and Dryl showed that P. caudatum
      incubated in 15 mM K(+) for over 15 min fail to give avoiding reactions when
      challenged with Ba(2+) or a thermal gradient [Hildebrand, E. & Dryl, S. (1976)
      Bioelectrochem. Bioenerg. 3, 543-544]. We have observed a similar phenomenon in
      wild-type P. tetraurelia. However, the K(+)-resistant mutants show little or no
      such "adaptation," i.e., they perform avoiding reactions when challenged with
      Ba(2+) after prolonged incubation in 15 mM K(+). The K(+) resistance and the lack
      of "adaptation" are strictly correlated. Because all 33 lines of mutants show
      this correlation, "adaptation" and killing by K(+) must share a mechanism. This
      mechanism may be studied by finding the basis of the K(+) resistance in the
      mutants. The possible ionic bases of "adaptation" are discussed.

PMID- 16592589
TI  - Stability in dynamical astronomy.
AB  - Hill's concept of stability is generalized and its relation to bifurcation theory
      is shown. A quantitative measure of stability is introduced that allows the
      comparison of the stability of different astronomical systems. Theoretical
      stability limits for triple stellar systems, for planetary systems, and for
      satellite systems are established. The measure of stability is evaluated for
      several known triple stellar systems as well as for the planets and for the
      natural satellites of the solar system. The model of the restricted problem of
      three bodies and values of the Jacobian constant are used to study planetary and
      satellite systems. The model of the general problem of three bodies is used to
      establish criteria for triple stellar systems.IN GENERAL, THE RESULTS SHOW A
      HIERARCHY OF STABILITY: the existing triple systems are more stable than the
      planetary orbits of the solar system. The satellites of the solar system are
      least stable; in fact, some of the satellites are close to the line of
      instability (the Earth's Moon) and some are actually unstable (the four outermost
      satellites of Jupiter).

PMID- 16592590
TI  - Fluorescence energy transfer in the rapid-diffusion limit.
AB  - Energy transfer is enhanced by translational diffusion of the donor and acceptor
      [Steinberg, I. Z. & Katchalski, E. (1968) J. Chem. Phys. 48, 2404-2410]. The
      effect of diffusion on energy transfer depends on Dtau(0)/s(2), in which D is the
      sum of the diffusion coefficients of the donor and acceptor, tau(0) is the
      lifetime of the donor in the absence of transfer, and s is the mean distance
      between donors and acceptors. In most previous studies, Dtau(0)/s(2) << 1,
      corresponding to the static limit. We report here steady-state and kinetic
      fluorescence experiments showing that Dtau(0)/s(2) >> 1, the rapid-diffusion
      limit, can be attained by using Tb(3+) chelated to dipicolinate as a long-lived
      energy donor (tau(0) = 2.2 msec). The concentration of rhodamine B, the energy
      acceptor, resulting in 50% transfer was 0.67 muM, which is three orders of
      magnitude less than the concentration giving 50% transfer in the static limit.
      The dependence of the transfer efficiency on diffusion coefficients varying from
      5 x 10(-11) to 1.5 x 10(-4) cm(2)/sec, spanning the range from the static limit
      to the rapid-diffusion limit, is in excellent agreement with theory. It is
      evident that energy donors with millisecond or longer excited state lifetimes can
      be used to probe translational motions in membranes and other assemblies. Energy
      transfer in the rapid diffusion limit is sensitive to the distance of closest
      approach (a) of the donor and acceptor. For a Tb.(DPA)(3) chelate trapped inside
      the aqueous space of a membrane vesicle containing eosin
      phosphatidylethanolamine, a = 10 A. The transverse location of chromophores in
      model membranes and biological membranes can be determined by this technique.

PMID- 16592591
TI  - Effect of rotational symmetry on colored lattices.
AB  - A colored lattice L(c) has a geometrical lattice L. A subgroup lattice L' of L
      and each of its cosets consist of like-colored points, each coset having a
      different color. The index of L' in L is given by Delta, the determinant of the
      matrix (t(jk)) that converts L into L'. This is the order of the factor group
      {L/L'}, and is also the number n of colors present. The crystal systems-i.e., the
      combinations of rotational symmetry axes-of L(c), L, and L' are all the same, but
      L and L' may have different centerings; this results in 39 combinations of
      centerings, called here the 39 symmetry types of colored lattices. These types
      are tabulated here, together with the special forms taken by (t(jk)) and the
      formulas for Delta. In only 7 of the 39 types can the number of colors be
      arbitrary; in most types certain numbers of colors are impossible.

PMID- 16592592
TI  - On the failure of the Drell-Yan parton model to account for production of the
      J/Psi in nucleon-nucleon interactions.
AB  - We calculate the cross sections for the production of the J/Psi in nucleon
      nucleon interactions on the basis of a naive Drell-Yan-type parton model where
      the Psi production is considered as production through the resonant or fusion
      interaction of quarks and antiquarks resident in the colliding nucleons. The
      interacting quarks are assumed to act as free point Dirac particles obeying the
      Bethe-Heitler description of annihilation to lepton pairs. Unitarity limits on
      Psi production established by calculations conducted on this basis are shown to
      be much smaller than the measured cross section, indicating that such models are
      unsatisfactory. Similar considerations suggest that the Psi production cannot be
      described by the interactions of nearly free gluons.

PMID- 16592593
TI  - Brilliant total reflection from a liquid-liquid interface.
AB  - In this paper I describe total reflection of great brilliancy that seems to
      indicate that an interface can be very thin.

PMID- 16592594
TI  - An amino-terminal fragment of lac repressor binds specifically to lac operator.
AB  - We have examined the effect of an aminoterminal peptide from the lac repressor
      (residues 1-59) on the methylation of purines in the lac operator with dimethyl
      sulfate. The peptide perturbs the methylation of the operator, and the peptide
      induced pattern of inhibition and enhancement of methylation, across the
      operator, closely resembles the pattern induced by intact repressor. This
      demonstrates that this small amino-terminal peptide binds specifically to the lac
      operator and that the mechanism of recognition and binding is basically the same
      as that of intact repressor.

PMID- 16592595
TI  - Structure of the oxygen adduct intermediate in the bacterial luciferase reaction:
      C nuclear magnetic resonance determination.
AB  - By using FMN enriched in (13)C (90%) at position C-4a, we have conclusively shown
      that the reaction of molecular oxygen with bacterial luciferase-bound FMNH(2)
      forms an adduct at the 4a position. Consistent with this are (13)C NMR studies of
      FMN and other flavin compounds which show that this carbon should be unusually
      reactive in the reduced 1,5-dihydroflavins with respect to electrophilic attacks.

PMID- 16592596
TI  - A third site of porton translocation in green plant photosynthetic electron
      transport.
AB  - Prereduction of the intersystem pool in isolated spinach chloroplasts leads to
      the appearance of a slow phase in the field-indicating 515-nm change induced by a
      flash. Measurements with the pH-indicator dye cresol red show that a proton
      uptake is associated with this slow 515-nm change. When water is the electron
      donor to photosystem II, electron transfer to ferricyanide is associated with the
      uptake of more than one proton per electron. Tetraphenylboron upon oxidation by
      system II releases a proton directly into the medium; yet, flash-induced electron
      transport from tetraphenylboron to ferricyanide is accompanied by a net uptake of
      protons from the medium. The above four results demonstrate the existence of two
      proton translocation sites in the chain between the two photoacts; the first two
      observations locate the new site at the oxidizing side of the plastoquinone pool.

PMID- 16592597
TI  - Post-translational transport into intact chloroplasts of a precursor to the small
      subunit of ribulose-1,5-bisphosphate carboxylase.
AB  - A precursor to the small subunit of ribulose-1,5-bisphosphate carboxylase [3
      phospho-D-glycerate carboxylyase (dimerizing), EC 4.1.1.39] has been identified
      among the products of cell-free translation of polyadenylated RNA from spinach
      and pea. In both cases, the precursor is larger than the mature protein by 4000
      5000 daltons. Upon incubation of post-ribosomal supernatants of the in vitro
      protein synthesis mixtures with purified intact chloroplasts, the pea and spinach
      precursors are transported interchangeably into the chloroplasts and processed to
      the mature size and charge. Moreover, the newly transported small subunits are
      found to assemble with endogenous large subunits to form the holoenzyme. In
      contrast, a precursor to the Chlamydomonas reinhardtii small subunit is not taken
      up by higher plant chloroplasts, indicating the specificity of the transport
      events. Together, these results demonstrate that the in vitro reconstruction of
      the post-translational transport of the higher plant precursors is
      physiologically significant.

PMID- 16592598
TI  - Kin selection: A classical approach and a general solution.
AB  - The necessary conditions for the spread of genes that determine social behaviors
      and the rate of spread of these genes are derived for a simple model (single
      locus, two alleles, random mating, discrete generations) by using the classical
      population genetics approach pioneered by Haldane and the linear fitness function
      used previously by D. S. Wilson. These results are derived for social behaviors
      that are manifested by individuals within families, within pairs of families, or
      within groups of k families, for both diploid and haplodiploid organisms. I show
      that, when the groups of socially interacting individuals consist of the members
      of more than one family, severe restrictions are placed on the evolution of
      altruistic and social behaviors. Specifically, in these instances, the necessary
      conditions for the evolution of social behaviors are more stringent and the rate
      of evolution is greatly reduced.

PMID- 16592599
TI  - High recovery of nitrogenase activity and of Fe-labeled nitrogenase in
      heterocysts isolated from Anabaena variabilis.
AB  - Heterocysts were isolated from the N(2)-fixing cyanobacterium Anabaena variabilis
      after vegetative cells were disrupted by treatment with lysozyme and cavitation
      in a sonic cleaning bath. The acetylene-reducing (nitrogenase) activity of the
      isolated heterocysts, ca. 5.0 mumol (mg of chlorophyll a)(-1) min(-1) in the
      presence of H(2) and light, accounted for an average of 60% of the nitrogenase
      activity of whole filaments, and was relatively insensitive to inactivation by
      oxygen. Soluble extracts derived from intact filaments grown with (55)Fe, and
      from their heterocysts and vegetative cells, were subjected to electrophoresis.
      The nitrogenase and nitrogenase reductase bands (MoFe protein and Fe protein, or
      component 1 and component 2, respectively) were identified in these nondenaturing
      gels, and their radioactivities were quantitated. The isolated heterocysts
      accounted for an average of 91% of the nitrogenase and 69% of the nitrogenase
      reductase of the original filaments.

PMID- 16592600
TI  - Generalizing Fisher's "reproductive value": "Incipient" and "penultimate"
      reproductive-value functions when environment limits growth; linear approximants
      for nonlinear Mendelian mating models.
AB  - In the usual Darwinian case in which struggle for existence leads to density
      limitations on the environment's carrying capacity, R. A. Fisher's reproductive
      value concept reduces to zero for every initial age group. To salvage some
      meaning for Fisher's notion, two variant reproductive-value concepts are defined
      here: an "incipient reproductive-value function," applicable to a system's early
      dilute stage when density effects are still ignorable; and a "second-order
      penultimate reproductive-value function," linking to a system's initial
      conditions near equilibrium its much later small deviations from carrying
      capacity equilibrium. Also, slowly changing age-structured mortality and
      fertility parameters of Lotka and Mendelian mating systems are shown to suggest
      linear reproductive-value surrogates that provide approximations for truly
      nonlinear diploid and haploid models.

PMID- 16592601
TI  - Classifications and comparisons of multilocus recombination distributions.
AB  - Various classifications and representations of multilocus recombination
      structures are delineated based on generalized notions of linkage values and
      recombination rates. An important class of recombination distributions (called
      the count-location chiasma process) is parameterized by a distribution of the
      number of crossover events and, for each such crossover count, by a conditional
      distribution of crossover locations. A number of properties of this recombination
      structure are developed. A multilocus definition of a "natural" recombination
      range is set forth. Orderings among recombination distributions in the multilocus
      setting are also discussed. Comparisons are made in terms of complete linkage,
      free assortment and noninterference schemes serving as standards.

PMID- 16592602
TI  - Benjamin-Ono-related equations and their solutions.
AB  - It is shown that the Benjamin-Ono equation is one of a hierarchy of nonlinear
      partial differential singular integral equations. Explicit multisoliton solutions
      are constructed for all equations of the hierarchy.

PMID- 16592603
TI  - 2,5-Dimethylfuran from approximately 2.7 x 10-year-old Rupemba-Belingwe
      stromatolite, Rhodesia: Potential evidence for remnants of carbohydrates.
AB  - 2,5-Dimethylfuran, 2-methylfuran, and C(9)-C(20)n-alkanes have been isolated from
      the kerogen of a Rupemba stromatolite. These furans could be the oldest known
      stable remnants of biological carbohydrates if it is possible to prove that their
      progenitors are as old as the rock. Experiments showed that it is improbable that
      these compounds are analytical artifacts or laboratory contaminations.
      Postdepositional contaminations caused by fluids flowing through the rocks seem
      doubtful because of minimal permeability, which is supported by petrographic
      observations. Contamination by diffusion also appears to be unlikely. Because the
      rock had a mild temperature history, these molecules could have survived since
      Archean time. Because of all the evidence, the furans and alkanes are quite
      likely biochemical fossils.

PMID- 16592604
TI  - Lithium dodecyl sulfate/polyacrylamide gel electrophoresis of thylakoid membranes
      at 4 degrees C: Characterizations of two additional chlorophyll a-protein
      complexes.
AB  - Lithium dodecyl sulfate/polyacrylamide gel electrophoresis of Chlamydomonas
      reinhardtii thylakoid membranes at room temperature gave two chlorophyll-protein
      complexes, CP I and CP II, as had been reported previously. However, when the
      electrophoresis was performed at 4 degrees C, there was an increase in the amount
      of chlorophyll associated with CP I and CP II, and in addition, three other
      chlorophyll-protein complexes appeared. Two of these complexes, designated CP III
      and CP IV, were characterized and found to be similar in their compositions. Each
      complex contains four to five molecules of chlorophyll a, one molecule of beta
      carotene, and one polypeptide chain. The apoprotein of CP III is polypeptide 5
      (M(r) 50,000) and that of CP IV is polypeptide 6 (M(r) 47,000); the two
      polypeptides are structurally unrelated. Chlorophyll-protein complexes similar to
      C. reinhardtii CP III and CP IV were also detected in higher plants (e.g., Pisum
      sativum). The apoproteins of the higher plant complexes are immunochemically
      related to those of the C. reinhardtii complexes, as shown by crossed
      immunoelectrophoresis. Absorption spectra of CP III and CP IV at -196 degrees C
      revealed a component at 682 nm. This observation, together with the previous
      results on photosystem II mutants [Chua, N.-H. & Bennoun, P. (1975) Proc. Natl.
      Acad. Sci. USA 72, 2175-2179], provides indirect evidence that CP III and CP IV
      may be involved in the primary photochemistry of photosystem II.

PMID- 16592605
TI  - Ethylene biosynthesis: Identification of 1-aminocyclopropane-1-carboxylic acid as
      an intermediate in the conversion of methionine to ethylene.
AB  - L-[U-(14)C]Methionine fed to apple tissue was efficiently converted to ethylene
      when the tissue was incubated in air. In nitrogen, however, it was not
      metabolized to ethylene but was instead converted to 1-aminocyclopropane-1
      carboxylic acid (ACC). When apple tissues were fed with L-[methyl
      (14)C]methionine or L-[(35)S]methionine and incubated in nitrogen, radioactivity
      was found subsequently in methylthioribose. This suggests that methionine is
      first converted to S-adenosylmethionine which is in turn fragmented to ACC and
      methylthioadenosine. Methylthioadenosine is then hydrolyzed to methylthioribose.
      The conclusion that ACC is an intermediate in the conversion of methionine to
      ethylene is based on the following observations: Labeled ACC was efficiently
      converted to ethylene by apple tissue incubated in air; the conversion of labeled
      methionine to ethylene was greatly decreased in the presence of unlabeled ACC,
      but the conversion of labeled ACC to ethylene was little affected by the presence
      of unlabeled methionine; and 2-amino-4-(2'-aminoethoxy)trans-3-butenoic acid, a
      potent inhibitor of pyridoxal phosphate-mediated enzyme reactions, greatly
      inhibited the conversion of methionine to ethylene but did not inhibit conversion
      of ACC to ethylene. These data indicate the following sequence for the pathway of
      ethylene biosynthesis in apple tissue: methionine --> S-adenosylmethionine -->
      ACC --> ethylene. A possible mechanism accounting for these reactions is
      presented.

PMID- 16592606
TI  - Is there a "hydrophobic effect"?
AB  - This paper presents facts that disagree with the hypothesis of "a hydrophobic
      effect."

PMID- 16592607
TI  - Purification of soluble guanylate cyclase from rat liver.
AB  - Soluble guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] has
      been purified from rat liver and exhibited a single protein band on
      polyacrylamide gels coincident with activity and indicative of a molecular weight
      of 150,000. The apparent specific activity of the purified enzyme was 276 nmol of
      cyclic GMP formed per mg per min with Mn(2+) as the cation cofactor and 23.8 nmol
      of cyclic GMP formed per mg per min with Mg(2+). This represented 9200-fold and
      7400-fold purifications of Mn(2+) and Mg(2+) activities, respectively. The
      specific activity of soluble guanylate cyclase was not constant with protein
      concentration. At all stages of purification, increasing the enzyme concentration
      in the guanylate cyclase assay increased the apparent specific activity of the
      preparation. The purified enzyme could be activated by nitroprusside, nitric
      oxide, arachidonate, linoleate, oleate, and superoxide dismutase. However, the
      degree of activation was dependent upon the concentration of enzyme protein
      assayed.

PMID- 16592608
TI  - Chloroplast membrane alterations in triazine-resistant Amaranthus retroflexus
      biotypes.
AB  - The effectiveness of diuron, atrazine, procyazine, and cyanazine were compared in
      controlling growth of redroot pigweed (Amaranthus retroflexus L.) in hydroponic
      culture. A very marked differential inhibition response was observed for atrazine
      between resistant and susceptible biotypes. Procyazine and cyanazine exhibited
      less dramatic differential responses, whereas diuron was equally effective in
      controlling growth in both biotypes. Photosystem II activity of chloroplasts from
      both triazine-resistant and triazine-susceptible biotypes was inhibited by diuron
      but only the chloroplasts from triazine-susceptible biotypes were inhibited
      significantly by atrazine. The photochemical activity of chloroplasts from
      triazine-resistant biotypes was partially resistant to procyazine or cyanazine
      inhibition. The parallel lack of diuron differential effects, partial procyazine
      and cyanazine differential response, and very marked atrazine differential
      response in both whole plant and chloroplast assays indicates that the
      chloroplast is the site of selective herbicide tolerance in these triazine
      resistant redroot pigweed biotypes.Photosystem II photochemical properties were
      characterized by analysis of chlorophyll fluorescence transients in the presence
      or absence of herbicides. Data with susceptible chloroplasts indicated that both
      diuron and atrazine inhibit electron flow very near the primary electron acceptor
      of photosystem II. Only diuron altered the fluorescence transient in resistant
      chloroplasts. In untreated preparations there were marked differences in the fast
      phases of the fluorescence increase in resistant vs. susceptible chloroplasts;
      these data are interpreted as showing that the resistant plastids have an
      alteration in the rate of reoxidation of the primary photosystem II electron
      acceptor. Electrophoretic analysis of chloroplast membrane proteins of the two
      biotypes showed small changes in the electrophoretic mobilities of two
      polypeptide species. The data provide evidence for the following herbicide
      resistance mechanism: genetically controlled modification of the herbicide target
      site.

PMID- 16592609
TI  - Strongly nonlinear parabolic initial-boundary value problems.
AB  - An existence and uniqueness result is presented for the solution of a parabolic
      initial-boundary value problem under Dirichlet null boundary conditions for a
      general parabolic equation of order 2m with a strongly nonlinear zeroth-order
      perturbation. This is the parabolic generalization of a class of elliptic results
      considered earlier by the writers and others and is based upon a new compactness
      theorem.

PMID- 16592610
TI  - Efficiency of truncation selection.
AB  - Truncation selection is known to be the most efficient form of directional
      selection. When this is modified so that the fitness increases linearly over a
      range of one or two standard deviations of the value of the selected character,
      the efficiency is reduced, but not greatly. When truncation selection is compared
      to a system in which fitness is strictly proportional to the character value, the
      relative efficiency of truncation selection is given by f(c)/sigma, in which f(c)
      is the ordinate of the frequency distribution at the truncation point and sigma
      is the standard deviation of the character. It is shown, for mutations affecting
      viability in Drosophila, that truncation selection or reasonable departures
      therefrom can reduce the mutation load greatly. This may be one way to reconcile
      the very high mutation rate of such genes with a small mutation load. The
      truncation model with directional selection is appropriate for this situation
      because of the approximate additivity of these mutations. On the other hand, it
      is doubtful that this simple model can be applied to all genes affecting fitness,
      for which there are intermediate optima and antagonistic selection among
      components with negative correlations. Whether nature ranks and truncates, or
      approximates this behavior, is an empirical question, yet to be answered.

PMID- 16592611
TI  - Unstable spiral modes in disk-shaped galaxies: A general fluid dynamical theory
      with some preliminary results.
AB  - A numerical scheme has been devised to calculate discrete spiral modes in a fluid
      dynamical model of disk galaxies. The procedure is free from the usual
      restrictions imposed upon the asymptotic theory. A radiation condition has been
      formulated as one of the boundary conditions. For a test model galaxy with
      moderately low surface density, quantitative agreement is found between the
      asymptotic spiral modes and the corresponding ones obtained from the present
      scheme. The present scheme should find ready application to the study of open
      spiral modes.

PMID- 16592612
TI  - Inverted repeats in chloroplast DNA from higher plants.
AB  - The circular chloroplast DNAs from spinach, lettuce, and corn plants have been
      examined by electron microscopy and shown to contain a large sequence repeated
      one time in reverse polarity. The inverted sequence in spinach and lettuce
      chloroplast DNA has been found to be 24,400 base pairs long. The inverted
      sequence in the corn chloroplast DNA is 22,500 base pairs long. Denaturation
      mapping studies have shown that the structure of the inverted sequence is highly
      conserved in these three plants. Pea chloroplast DNA does not contain an inverted
      repeat. All of the circular dimers of pea chloroplast DNA are found to be in a
      head-to-tail confirmation. Circular dimers of spinach and lettuce were also found
      to have head-to-tail conformation. However, approximately 70-80% of the circular
      dimers in preparations of lettuce and spinach chloroplast DNA were found to be in
      a head-to-head conformation. We propose that the head-to-head circular dimers are
      formed by a recombination event between two circular monomers in the inverted
      sequence.

PMID- 16592613
TI  - Dynamics of density- and frequency-dependent selection.
AB  - The evolution of a multiallelic locus in a diploid monoecious population is
      investigated for weak selection in both discrete and continuous time. It is
      assumed that in the absence of selection the rate of change of population size N
      is a function only of N, and N converges exponentially to a unique, globally
      stable equilibrium, ;N. With arbitrary density- and frequency-dependent
      selection, after several generations have elapsed, N differs from ;N by terms of
      O(s) (i.e., bounded by a constant times s), where s is the selection intensity.
      The mean absolute fitness deviates from its equilibrium value (1 in discrete, 0
      in continuous time) by only O(s(2)); its rate of change is O(s(3)). The evolution
      of the gene frequencies may be approximated with an error of O(s) by assuming
      that N = ;N and Hardy-Weinberg proportions obtain. When the frequency dependence
      is weaker than the selection intensity, the mean absolute fitness generally
      exceeds its equilibrium value by a quantity approximately proportional to the
      genic variance, the constant of proportionality being simply related to the rate
      of convergence of N to ;N in the absence of selection. Thus, after a short time,
      the population generally increases, and the rate of growth is proportional to the
      genic variance.

PMID- 16592614
TI  - Principles of polymorphism and epistasis for multilocus systems.
AB  - The nature of stable equilibrium configurations is described for general
      nonepistatic and generalized symmetric viability regimes in multilocus systems
      under conditions of tight and loose linkage. The influence of epistasis and
      symmetry can be better understood in terms of these standards. A dichotomy in the
      nature of stable polymorphisms emerges. More recombination, bisexuality, and
      multideme interactions facilitate the establishment of central type
      polymorphisms.

PMID- 16592615
TI  - Self-avoiding random walks at finite concentrations: The bulk phase limit.
AB  - In infinitely dilute solutions, macromolecules exhibit non-Gaussian distributions
      for their end-to-end separations. This occurs under such circumstances because
      intramolecular interactions are more important than intermolecular forces. On the
      other hand, when a macromolecular solution becomes so concentrated that it
      approaches its bulk phase, then the end-to-end length distribution becomes
      substantially Gaussian. A theoretical explanation for the observed behavior is
      obtained by taking cognizance of a balance between inter-and intramolecular
      forces acting on self-avoiding random chains. Such a balance causes the chains to
      behave very much like random walks of order 2-that is to say, walks for which the
      only restriction against double occupancy is that identified with immediate
      return steps. This is demonstrated by taking Monte Carlo data for chains of
      various concentrations and analyzing the distributions of a component of length
      by using expansions involving orthogonal vectors. Although Gaussian behavior is
      more or less achieved for bulk polymers, slight deviations from that behavior
      still persist at the origin.

PMID- 16592616
TI  - Gravitational interaction of hadrons and leptons: Linear (multiplicity-free)
      bandor and nonlinear spinor unitary irreducible representations of SL(4R).
AB  - We review two possible affine extensions of gravity connected to the strong
      interactions. In the metric affine theory, torsion and nonmetricity do not
      propagate, gravitation is effectively unmodified, and the observed approximate
      conservation of hadron intrinsic hypermomentum-i.e., scaling, SU(6), and Regge
      trajectories-is due to the GL(4,R) band-spinor structure of the hadrons. In the
      second approach, the new gravitational Lagrangian density generates propagating
      but confined torsion and nonmetricity, presumably the main contributions to quark
      confinement. Leptons are represented nonlinearly as Poincare spinors with the
      metric field as "realizer" and Higgs boson, and are unconfined. We present a
      construction for all linear multiplicity-free (= bandor) representations of
      GL(4,R) and in particular the [Formula: see text] fitting the hadron manifield.
      We also construct the Hilbert space hadron states [irreps (irreducible
      representations) of GA(4,R)] and the nonlinear realizations of GL(4,R) for lepton
      fields.

PMID- 16592617
TI  - Localized deposition of chitin on the yeast cell surface in response to mating
      pheromone.
AB  - Treatment of a mating-type Saccharomyces cerevisiae cells with the pheromone
      alpha-factor (secreted by alpha mating-type cells) induces the synthesis of
      chitin. Small daughter cells, which start with no detectable chitin, make 3 times
      more chitin when grown in the presence of alpha-factor than do untreated
      exponentially growing cells. Budding cells accumulate chitin in the nascent
      division septum [Cabib, E. & Bowers, B. (1975) J. Bacteriol. 124, 1586), as
      detected by staining with the fluorescent dye primulin. In the absence of a
      division septum, alpha-factor-treated cells accumulate chitin in the area of
      pheromone-stimulated growth. Enzymatic lysis of budding and pheromone-treated
      cells allows the separation of membrane-bound chitin synthase (UDP-2-acetamido-2
      deoxy-D-glucose: chitin 4-beta-acetamidodeoxyglucosyltransferase, EC 2.4.1.16)
      activity from a dense particulate fraction containing chitin. Chitin synthase
      activity is associated with both the plasma membrane and small intracellular
      particles. During pheromone treatment, the levels of chitin synthase in the
      plasma membrane and in intracellular particle fractions increase 11- and 4-fold,
      respectively. Although chitin synthase is made as zymogen that requires
      proteolytic activation, the plasma membrane of pheromone-treated cells shows a
      significant fraction of preactivated enzyme; intracellular membrane-bound
      synthase is found exclusively in the zymogen form.

PMID- 16592618
TI  - C nuclear magnetic resonance study of the CO(2) activation of
      ribulosebisphosphate carboxylase from Rhodospirillum rubrum.
AB  - Ribulosebisphosphate carboxylase [3-phospho-D-glycerate carboxy-lyase
      (dimerizing), EC 4.1.1.39] from Rhodospirillum rubrum is activated by CO(2) and
      Mg(2+). (13)C NMR spectra were determined for the unactivated enzyme and for
      enzyme that had been activated by (13)CO(2) and Mg(2+). In addition to the
      expected resonance for H(13)CO(3) (-)/CO(3) (2-) at 161.8 ppm downfield from
      tetramethylsilane, the spectrum of the activated enzyme shows a broad resonance
      at 164.9 ppm. Analogy with previous NMR studies of (13)CO(2) binding to
      hemoglobin [Morrow, J. S., Keim, P., Visscher, R. B., Marshall, R. C. & Gurd, F.
      R. N. (1973) Proc. Natl. Acad. Sci. USA 70, 1414-1418], to myoglobin, and to
      amino acids [Morrow, J. S., Keim, P. & Gurd, F. R. N. (1974) J. Biol. Chem. 249,
      7484-7494] suggests that the CO(2) activation of ribulosebisphosphate carboxylase
      involves formation of a carbamate between an enzyme amino group and CO(2).

PMID- 16592619
TI  - Cryoenzymology in aqueous media: Micellar solubilized water clusters.
AB  - Amphiphilic compounds dissolved in nonpolar organic solvents form inverted
      micelles whose aqueous centers can solubilize relatively large amounts of
      enzymes. The solutions are homogeneous and optically transparent and have low
      viscosity and freezing points; they provide unique and favorable systems to
      perform the main cryoenzymologic studies previously carried out in mixed
      solvents. The preparation and properties of such micelles are described. The
      absorbance spectra of cytochrome c at various temperatures from -38 degrees C to
      20 degrees C are given. The pH dependence of trypsin-catalyzed hydrolysis of
      benzoylarginine ethyl ester in inverted micelles, as well as kinetic properties
      and activation energy, is described. Some problems are analyzed.

PMID- 16592620
TI  - Steady-state phase or cooperative transitions between biochemical cycles.
AB  - In a steady-state lattice of interacting enzyme molecules that have a multicycle
      kinetic diagram, a cooperative or phase transition may involve not only the
      conventional sudden change in the relative importance of the different states of
      a molecule but also a sudden change in the dominant cycles of the diagram. The
      latter effect implies a sudden switch in the dominant biochemistry (e.g., a
      sudden onset of active transport). An explicit example is discussed.

PMID- 16592621
TI  - Spectral and kinetic evidence for two early electron acceptors in photosystem I.
AB  - Triton-fractionated photosystem-I particles poised at -625 mV, where the two
      bound iron-sulfur proteins are reduced, have been studied by optical and electron
      paramagnetic resonance spectroscopies from 293 to 5 K. At 5-9 K, these particles
      exhibit two decay components with lifetimes of 1.3 and 130 msec in the laser
      pulse-induced absorption and electron paramagnetic resonance signal changes.
      Spectral properties of the 130-msec decay component reflect the charge separation
      between P-700 and some iron-sulfur center having a broad optical absorbance in
      the 400- to 550-nm region and a previously reported electron paramagnetic
      resonance signal with g = 1.78, 1.88, and 2.08. Spectral properties of the 1-msec
      decay component indicate photoinduced charge separation between P-700 and a
      chlorophyll a dimer having absorption bands at 420, 450, and 700 nm. It is
      assumed that these two acceptors participate in the electron transfer from P
      700(*) to the bound iron-sulfur proteins.

PMID- 16592622
TI  - Vibrational analysis of peptides, polypeptides, and proteins: Characteristic
      amide bands of beta-turns.
AB  - Normal vibration calculations have been done for a type I beta-turn of CH(3)-CO
      (Ala)(4)-NH-CH(3) and a type II beta-turn of CH(3)-CO-(Ala)(2)-Gly-Ala-NH-CH(3).
      The force field was the one we refined for beta-sheet and alpha-helical
      structures. A calculation was also done for CH(3)-O-CO-Gly-(Ala)(2)-Gly-O-CH(3),
      which is an appropriate model for two tetrapeptides for which infrared data are
      available. The agreement between observed and calculated frequencies in this case
      is good, thus supporting the conclusions drawn from the above beta-turn
      calculations. The most important result of the calculations is the prediction of
      bands near 1690 cm(-1), a region heretofore associated only with the antiparallel
      chain pleated sheet structure. This means that bands observed in proteins near
      1690 cm(-1) should be associated with the presence of beta-turns as well as of
      beta-sheets. We also find that a band near 1665 cm(-1) is characteristic of type
      II turns.

PMID- 16592623
TI  - Dependence of thermal responses of seeds on membrane transitions.
AB  - Transitions at 28-32 degrees C in membranes of many kinds of seeds influence
      their germination and subsequent growth. Changes at 28-32 degrees C in the rates
      of loss of endogenous amino acids from imbibed Barbarea verna and Lactuca sativa
      seeds indicate permeation of the plasma membrane. A transition in the same
      temperature range is shown by the change in fluorescence with temperature of
      substituted naphthalenesulfonate probe molecules associated with membrane
      fragments isolated from the seeds. Some other plant responses that appear to be
      causally connected with the membrane(s) transition(s) in the 28-32 degrees C
      region are growth of maize seedlings and tomato roots, flowering of some bulbs,
      and control of seed and fern spore germinations by light. Generality of the
      control is indicated.

PMID- 16592624
TI  - Apparent dependence of sporulation on synthesis of highly phosphorylated
      nucleotides in Bacillus subtilis.
AB  - Bacillus subtilis contains an enzyme that synthesizes the highly phosphorylated
      nucleotide adenosine 5',3'(2')-bis(triphosphate), abbreviated p(3)Ap(3). This
      enzyme can be demonstrated to be present in the cytoplasmic membrane of B.
      subtilis at all stages of growth and development. During vegetative growth its
      enzymatic activity is inhibited by phosphorylated metabolites of energy-rich
      carbon sources, as was shown with the aid of conditional sporulation mutants. The
      finding that a temperature-sensitive sporulation mutant with a mutation in the
      spoOF gene, an early sporulation gene, shows a temperature-sensitive activity of
      p(3)Ap(3)-synthetase indicates that p(3)Ap(3) plays an important role in
      sporulation, probably initiation of sporulation.

PMID- 16592625
TI  - Maximum geographic range of a mutant allele considered as a subtype of a Brownian
      branching random field.
AB  - A rare allelic type is modeled as a field of individuals diffusing independently
      in d-dimensional space (d = 1,2,...), in which individuals are replaced by random
      numbers of offspring at a constant rate. In an infinite-allele model with
      selectively identical alleles, the offspring distribution would have mean 1 - u,
      in which u is the mutation rate; otherwise mean (1 - u)w, in which w is the
      relative fitness of the allele. Let p(x) be the probability that some descendent
      of an individual initially at zero diffuses unilaterally as far as x(d = 1), or
      else the probability that some descendent of an individual at x diffuses within a
      > 0 of the origin (d >/= 2). A nonlinear differential equation is found for p(x)
      that is solvable for d = 1 and related to Emden's equation for d >/= 2. For p(x)
      >/= 10(-4) and u </= 10(-5), genetic drift is more important than mutation in the
      behavior of p(x) (d = 1). If u = 0 and w = 1, p(x) approximately C/x(2) as x -->
      infinity for d </= 3. As a mathematical application, it is shown that if the
      initial distribution is uniform Poisson, a bounded open set K is visited by
      individuals in the field at arbitrarily large times if d >/= 2 but not if d = 1.

PMID- 16592626
TI  - Regularity of the Dirichlet problem for the complex Monge-Ampere equation.
AB  - Regularity up to the boundary of the solutions of a boundary value problem for a
      complex Monge-Ampere equation on perturbations of an annulus in C(n) is proven.
      The result can be applied to the classification of such domains.

PMID- 16592627
TI  - Complete manifolds with nonnegative scalar curvature and the positive action
      conjecture in general relativity.
AB  - We find some integrability conditions for low-dimensional manifolds to admit
      metrics with nonnegative scalar curvature. In particular, we solve the positive
      action conjecture in general relativity in the affirmative.

PMID- 16592628
TI  - H theory for the poly-disc.
AB  - We show that the H(p) spaces on the bi-disc can be characterized in terms of
      either the nontangential maximal function and the area integral or their
      probabilistic analogues resulting by introducing two-time Brownian motion (i.e.,
      the martingale maximal function) and the corresponding square function.

PMID- 16592629
TI  - Higher plant chloroplasts: Evidence that all the chlorophyll exists as
      chlorophyll-protein complexes.
AB  - By using the polyacrylamide gel electrophoresis system described in this report,
      it was possible to fractionate all the photosynthetic pigments of maize (Zea mays
      L.) thylakoids into chlorophyll-protein complexes with negligible formation of
      free or detergent-complexed chlorophyll. Identical sodium dodecyl sulfate
      extracts of thylakoids have previously resulted in up to 50% of the chlorophyll
      migrating as free chlorophyll after electrophoresis. The major difference from
      previous gel electrophoresis systems is the replacement of sodium dodecyl sulfate
      in the electrophoresis buffer by Deriphat 160 (disodium N-lauryl-beta
      iminodipropionate), a zwitterionic detergent. The results suggest that: (i) no
      significant amount of free chlorophyll exists in the chloroplast thylakoid
      membranes in vivo, and (ii) most of the free pigment seen previously on gels was
      generated during the electrophoresis and was not a result of the solubilization
      technique. Additionally, the new chlorophyll-protein complexes resolved appear to
      have different characteristics (pigment content and size) that those observed in
      former systems.

PMID- 16592630
TI  - Large electrical currents traverse developing Ceropia follicles.
AB  - An intense (up to 20 muA/cm(2)) steady electrical current enters the anterior or
      nurse cell end of the growing follicle (or oocyte-nurse cell complex) of the
      Cecropia moth and is balanced by a more diffuse current leaving elsewhere. In
      late growth stages, the total transfollicular current is about 100 nA. Moreover,
      a separate small current, of about 1 nA, seems to leave the furrow between the
      oocyte and the nurse cells. After the nurse cells collapse, but before shell
      formation, the transfollicular current is redistributed so that a second
      relatively localized inward current appears at the posterior pole of the
      follicle. Thus, at this later stage currents enter both poles of the follicle and
      leave its sides. Previous measurements, with intracellular microelectrodes, seem
      to imply a very large (order of 1000 nA) back current across the cytoplasmic
      bridge between the oocyte and nurse cells. A simple model is presented that
      attributes the apparent bridge current, and the more directly measured
      transfollicular and furrow currents, to the action of an ion pump lying within
      the nurse cell face of the furrow membrane.

PMID- 16592631
TI  - Bird niches in a subalpine forest: An indirect ordination.
AB  - Multivariate techniques that are tolerant of the curvilinearity in population
      responses can be used to ordinate bird species in a niche hyperspace and to
      quantify niche relationships. Multidimensional scaling, secondary reciprocal
      averaging, and reciprocal averaging followed by principal components analysis
      give similar results in an ordination of 20 bird species in a spruce-fir forest.
      The ordination represents the organization of the bird community in relation to
      niche axes and suggests grouping of the bird species into guilds. A group of
      foliage-gleaning insectivores that finely divide their resource base is central
      to the bird community; other groups of species (ground feeders, aerial feeders,
      conifer specialists, and bark probers and peckers) have broader niches.

PMID- 16592632
TI  - Allelic pairing and gene regulation: A model for the zeste-white interaction in
      Drosophila melanogaster.
AB  - Data are presented that indicate that the z locus of Drosophila melanogaster
      represses w locus activity, but the repression is effective only on paired or
      physically adjacent w loci. Various mutant alleles of z and w were combined in a
      series of different doses to determine the effect of dosage and physical position
      in the nucleus on gene expression. In z/z individuals, paired white alleles fail
      to be expressed, while unpaired alleles are expressed normally. The results are
      discussed in terms of a model postulating that the z gene product represses the
      transcription of w(+) by complexing with an RNA produced by part of the white
      locus itself. In order to be effective in repression, there must be two w(+)
      genes producing the RNA in a limited volume in the nucleus. Such a model
      necessarily imposes a specific architecture on the chromatin of interphase
      nuclei.

PMID- 16592633
TI  - Model nebulae and determination of the chemical composition of the Magellanic
      Clouds.
AB  - An analysis of previously presented photoelectric spectrophotometry of HII
      regions (emission-line diffuse nebulae) in the two Magellanic Clouds is carried
      out with the aid of theoretical nebular models, which are used primarily as
      interpolation devices. Some advantages and limitations of such theoretical models
      are discussed. A comparison of the finally obtained chemical compositions with
      those found by other observers shows generally a good agreement, suggesting that
      it is possible to obtain reliable chemical compositions from low excitation
      gaseous nebulae in our own galaxy as well as in distant stellar systems.

PMID- 16592634
TI  - Self-avoiding random walks on lattice strips.
AB  - A self-avoiding walk on an infinitely long lattice strip of finite width will
      asymptotically exhibit an end-to-end separation proportional to the number of
      steps. A proof of this proposition is presented together with comments concerning
      an earlier attempt to deal with the matter. In addition, some unproved, yet
      "obvious," conjectures concerning self-avoiding walks are cited as basic
      propositions requiring study.

PMID- 16592635
TI  - Conformation of uncomplexed natural antamanide crystallized from CH(3)CN/H(2)O.
AB  - Natural antamanide, a cyclic decapeptide from Amanita phalloides, has been shown
      to have the same conformation for the backbone and comparable side groups as the
      biologically active synthetic [Phe(4), Val(6)]antamanide. Packing in the crystal
      is quite different for the two compounds. Large channels with a polar lining are
      formed in the crystals of [Phe(4), Val(6)]antamanide, whereas in natural
      antamanide large channels in the crystal are completely surrounded by the
      lipophilic side groups of the Pro, Phe, and Ala residues. Antamanide,
      C(64)H(78)N(10)O(10).8H(2)O.X, crystallizes in space group P2(1)2(1)2(1) with a =
      15.88 A, b = 34.88 A, and c = 13.61 A.

PMID- 16592636
TI  - Secular change in the variability of temperature.
AB  - The mean temperatures for January, April, summer and October at New Haven,
      Connecticut, for 1781-1970 were analyzed for evidence of a secular change in
      several indices of variability. The January-July difference decreased
      significantly. Although the standard deviation (SD) of the summer temperature
      within decades decreased significantly, the SDs of January, April, and October
      did not, and none of the SDs were correlated with means. The SD about trends
      within decades was not correlated with the magnitude of the trends except in
      April. There was no significant trend in the January-to-January persistence
      during the 19 decades.

PMID- 16592637
TI  - Stability and gap phenomena for Yang-Mills fields.
AB  - It is shown that any weakly stable Yang-Mills field of type SU(2) or SU(3) on the
      four-sphere must be self-dual or anti-self-dual. Any Yang-Mills field on S(n), n
      >/= 5, is unstable. Examples of stable fields on S(4) and S(n)/Gamma for n >/= 5
      and Gamma not equal {e} are given. It is also shown that, for any Yang-Mills
      field R on S(4), the pointwise condition parallelR(-) parallel (2) < 3 (or
      parallelR(+) parallel (2) < 3) implies that R(-) = 0 (or respectively that R(+) =
      0). In general, any Yang-Mills field R on S(n), n >/= 3, that satisfies the
      pointwise condition parallelR parallel(2) < (1/2)((2) (n)) is trivial. If n = 3
      or 4, the condition parallelR parallel(2) </= (1/2)((2) (n)) implies that either
      R is the trivial field or it is the direct sum of a trivial field with a field of
      tangent spinors carrying the standard connection.

PMID- 16592638
TI  - On integral representations for the Neumann operator.
AB  - This paper is devoted to the derivation of an approximate formula for the kernel
      of the Neumann operator N on strongly pseudo-convex domains. In particular, a new
      class of singular integral operators arises that are infinitely smoothing in the
      interior and preserve singular supports at the boundary and whose kernels are
      products of isotropic kernels with parabolic ones.

PMID- 16592639
TI  - Blow-up of solutions of nonlinear wave equations in three space dimensions.
AB  - Solutions u(x, t) of the inequality squareu >/= A|u|(p) for x epsilon R(3), t >/=
      0 are considered, where square is the d'Alembertian, and A,p are constants with A
      > 0, 1 < p < 1 + radical2. It is shown that the support of u is compact and
      contained in the cone 0 </= t </= t(0) -|x - x(0)|, if the "initial data" u(x,
      0), u(t)(x, 0) have their support in the ball|x - x(0)| </= t(0). In particular,
      "global" solutions of squareu = A|u|(p) with initial data of compact support
      vanish identically. On the other hand, for A > 0, p > 1 + radical2, global
      solutions of squareu = A|u|(p) exist, if the initial data are of compact support
      and "sufficiently" small.

PMID- 16592640
TI  - Evolution of olfactory receptor in oriental fruit fly Dacus dorsalis.
AB  - Male oriental fruit flies (Dacus dorsalis) from colonies in Taiwan and Hawaii
      were evaluated for limit of response to various analogues of methyl eugenol. The
      results are interpreted in terms of the geometry and allosteric requirements of
      the antennal receptor that triggers the characteristic methyl eugenol reflex.
      This receptor has evolved for complementarity to all portions of the methyl
      eugenol molecule and responds only to ortho-substituted benzenes with adjacent
      oxygen atoms or isoelectronic equivalents. Substantial differences in responses
      of Taiwan and Hawaiian D. dorsalis suggest that perceptible evolution of the
      receptor protein has occurred during the past 50 years. A plausible scheme for
      the coevolution of dacini flies with plants containing phenylpropionoid essential
      oils is outlined.

PMID- 16592641
TI  - Xylem and nonxylem cell formation in cytokinin-stimulated root tissue:
      Quantitative analysis of temperature effects.
AB  - Xylogenesis in mature root parenchyma is elicited in vitro by the concerted
      action of the hormones cytokinin and auxin. Decreasing the temperature delayed
      the initiation of xylogenesis relative to the initiation of nonxylem cell
      formation. Once xylem or nonxylem cell formation was initiated, its rate was not
      temperature-sensitive within the 10-25 degrees C range. Lowering the temperature
      after xylem formation had been initiated had little effect on xylem cell
      formation. Xylogenesis sensitivity to low temperature was demonstrable from the
      time cultures were established, even though cell division did not occur until 48
      72 hr later and overt xylogenesis did not occur until 6 or 7 days later. The cold
      sensitivity of xylogenesis is not limited to a unique or early phase of culture.

PMID- 16592642
TI  - Change in a secondary sexual character as evidence of incipient speciation in
      Drosophila silvestris.
AB  - Search for genetic changes that are pivotal in species formation has led to
      intraspecific studies of Drosophila silvestris, a giant species found only on the
      geologically new island of Hawaii. Males bear large, curved, modified bristles or
      cilia on the dorsal surface of the foreleg tibia and tarsus. In males from the
      south and west parts of the island there are two rows of cilia separated by a
      naked area, but in males from the north and east there is a mean of between 20
      and 30 additional cilia between the two major rows on the tibia. These extra
      cilia are absent in closely related species of this subgroup, including the
      sympatric species D. heteroneura and three species from adjacent islands. Males
      use the foreleg tibiae in vibratory movements against the female's abdomen during
      courtship, so this character difference is likely to be important in the
      reproductive biology of the species. Inversion polymorphisms are similar in both
      northeast and southwest populations; they show large and strikingly parallel
      altitudinal shifts in frequency distributions involving the same inversions.
      Populations from various parts of the island cannot be distinguished by routine
      electrophoresis of soluble proteins encoded by 25 loci. Thus the "extra cilia"
      character is superimposed on a more ancient genetic background of similarity
      involving both chromosomal and electrophoretic polymorphisms. We interpret the
      extra cilia as a specific new embellishment of a secondary sexual character
      brought about by altered sexual selection occurring very recently in one part of
      the species range. This suggests incipient speciation.

PMID- 16592644
TI  - Triplet phase invariants: Formula for centric case from fourth-order
      determinantal joint probability distributions.
AB  - A formula is derived for centrosymmetric crystals from fourth-order determinantal
      joint probability distributions that provides, for the triplet invariants, values
      of P(+)/P(-), the ratio of the probability that an invariant has a plus sign
      associated with it to the probability that it has a minus sign. The formula makes
      use of the entire data set in the computations for each invariant. Test
      calculations indicate that many hundreds of invariants can be selected by use of
      the formula with essential certainty that their value is equal to zero. Several
      invariants whose value is equal to pi can also be selected on occasion with very
      high reliability.

PMID- 16592643
TI  - Mutation of the non-Mendelian suppressor, Psi, in yeast by hypertonic media.
AB  - The Psi(+) extrachromosomal determinant in the yeast Saccharomyces cerevisiae
      suppresses certain UAA markers and increases the efficiency of suppression of UAA
      suppressors and certain frameshift suppressors. Although the exact nature of
      Psi(+) determinant is unknown, it is believed to be a self-replicating
      cytoplasmic factor affecting some component of the translational machinery. In
      this report we describe growth conditions for efficient mutation or elimination
      of the Psi(+) determinant. Incubation of Psi(+) cultures in hypertonic nutrient
      medium resulted in rapid conversion to a culture containing predominantly Psi(-)
      cells during the growth cycle. The kinetics of Psi(+) to Psi(-) conversion
      established that the occurrence of Psi(-) cells was due to induction and not to
      selection of pre-existing Psi(-) cells. The results suggest that the replication
      of the Psi(+) determinant is sensitive to hypertonic conditions.

PMID- 16592645
TI  - Metal cluster chemistry: Structure and stereochemistry in the polynuclear rhodium
      hydrides H(n)Rh(n)[P(OR)(3)](2n).
AB  - Crystallographic analyses of x-ray and neutron diffraction data have provided a
      definitive structural representation of {HRh[P(O-i-C(3)H(7))(3)](2)}(2) and
      {HRh[P(OCH(3))(3)](2)}(3). These polynuclear hydrides are generated from square
      planar H(2)Rh[P(OR)(3)](2) units by edge (hydrogen atom) sharing and by vertex
      (hydrogen atom) sharing to form the dimeric and trimeric structures,
      respectively. The square-planar units are held together through four-center and
      three-center two-electron Rh-H-Rh bonds in the dimer and trimer, respectively.
      The dimer and trimer molecules each add one molecule of hydrogen to form H[(i
      C(3)H(7)O)(3)P](2)RhH(3)Rh [P(O-i-C(3)H(7))(3)](2) and
      H(5)Rh(3)[P(OCH(3))(3)](6), respectively. NMR spectral information has served to
      define the stereochemical features of these polyhydrides. The significance of
      this chemistry in the metal cluster-metal surface analogy is described.

PMID- 16592646
TI  - On the spectral geometry of spaces with cone-like singularities.
AB  - I describe an extension of a portion of the theory of the Laplace operator on
      compact riemannian manifolds to certain spaces with singularities. Although this
      approach can be extended to include quite general spaces, this paper will confine
      itself to the case of manifolds with cone-like singularities. These singularities
      are geometrically the simplest possible, but they already serve to illustrate new
      phenomena that are typical of the more general situation. Moreover, by inductive
      arguments, the study of simplicial complexes whose simplices have constant
      curvature and totally geodesic faces (e.g., p.l. manifolds) can in large measure
      be reduced to the study of cone-like singularities.

PMID- 16592647
TI  - Complex-analyticity of harmonic maps and strong rigidity of compact Kahler
      manifolds.
AB  - A harmonic map f between two compact Kahler manifolds is shown to be either
      holomorphic or conjugate holomorphic under a suitable negativity condition on the
      curvature of the image manifold and a condition on the rank of df. As a
      consequence, a compact Kahler manifold of dimension >/=2 that is of the same
      homotopy type as a compact Kahler manifold with suitable negative curvature
      condition or as a compact quotient of an irreducible classical bounded symmetric
      domain must be either biholomorphic or conjugate biholomorphic to it.

PMID- 16592648
TI  - Numerical analysis of weakly nonlinear wave turbulence.
AB  - We consider the propagation of weakly nonlinear waves such as plasma waves,
      surface water waves, the interaction of laser beams with matter, particle
      accelerators, etc. Specifically, we study internal waves in the ocean. Hamilton's
      principle is used to write the fluid equations in Hamiltonian form in terms of
      linear eigenmode amplitudes. Numerical studies are made of the effect of Fourier
      grid size and resonance widths. Statistical information is generated from an
      ensemble of initial states of the random wave field.

PMID- 16592649
TI  - Irreversible processes at nonequilibrium steady states.
AB  - It is shown that a Liapunov criterion exists for the stability of nonequilibrium
      steady states. This criterion is based upon the fluctuation-dissipation relation,
      as was first pointed out by Keizer. At steady states, the Liapunov function is
      constructed from the covariance matrix for the thermodynamic variables. Unlike
      the situation around equilibrium, at steady states the covariance matrix and the
      "excess entropy" matrix are not equivalent. The excess entropy, which serves as
      the Liapunov function around equilibrium, does not work in this capacity at
      steady states. Keizer's Liapunov function must be viewed as the first correct
      candidate for a proper Liapunov function for steady states.

PMID- 16592650
TI  - Transcription program of the chloroplast genome of Euglena gracilis during
      chloroplast development.
AB  - RNA transcription in Euglena gracilis chloroplasts has been characterized by
      hybridization of RNA from cells at different stages of chloroplast development to
      (3)H-labeled chloroplast DNA restriction endonuclease fragments. Chloroplast DNA
      was digested into five fragments of 53,000, 35,000, 25,000, 10,000, and 6900 base
      pairs with Pst I. The 53,000-base-pair DNA was further cleaved by BamHI
      digestion. Eight different DNA fragments, of known restriction nuclease map
      location and accounting for the entire genome, were labeled in vitro by means of
      the nick translation reaction of DNA polymerase I with [(3)H]dTTP as a substrate.
      RNA was isolated from dark-adapted Euglena cells, and from cells at an early (4
      hr) and a late (72 hr) stage of light-induced chloroplast development. The RNAs
      were hybridized in solution to each (3)H-labeled chloroplast DNA fragment. From
      the extents and kinetics of the reactions, a temporal program for RNA
      transcription from defined regions of the chloroplast genome could be described.
      Different classes of transcription units are present, including RNAs (i)
      continuously present throughout development, (ii) induced at the onset of
      development, (iii) repressed early in development, and (iv) induced late in
      development.

PMID- 16592651
TI  - Relation between leaf senescence and stomatal closure: Senescence in light.
AB  - Senescence of isolated oat seedling leaves, floating on water or solutions in
      white light, has been followed by the disappearance of chlorophyll and the
      liberation of free amino nitrogen. In parallel, measurements of stomatal aperture
      were made with a diffusion resistance porometer, and borne out also by changes in
      fresh weight. The stomata open as expected in the light but slowly begin to close
      after the first day; correspondingly, in the dark they close at once but
      gradually begin to open on successive days. Abscisic acid causes closure and this
      is accompanied by senescence. Phenylmercuric nitrate also causes closure and
      again the reaction is closely paralleled by senescence. Kinetin maintains
      stomatal opening even more than does light alone, and this is accompanied by
      complete prevention of chlorophyll loss for at least 5 days. Covering the leaf
      surface with a film of Vaseline, especially when detergents are added,
      accelerates senescence. Merely floating the leaf segments on hypertonic solutions
      of sucrose or mannitol suffices to bring the rate of senescence in light up to
      the rate in darkness. It is concluded that the effect of light in delaying
      senescence is primarily due to its effect on the stomatal aperture, and, more
      generally, that stomatal aperture is the principal controlling agent in leaf
      senescence.

PMID- 16592652
TI  - Tabanomyces milkoi (Dudka and Koval) emended, genus novum, a fungal pathogen of
      horseflies.
AB  - A fungus originally described as a new species of Coelomomyces (C. milkoi) from
      larval Tabanidae in the Ukraine, USSR, is transferred to a new genus,
      Tabanomyces, and described in detail. The zygospores germinate to form a linear
      four-celled conidiophore, each cell producing a spherical conidium ejected as in
      Conidiobolus, thus confirming that the organism belongs in the Entomophthorales.
      The resemblance between the conidiophore of Tabanomyces milkoi and the basidium
      of the rusts supports the old concept that the rust fungi may be related to the
      Entomophthorales.

PMID- 16592653
TI  - Roles of actin during sporocarp culmination in the simple mycetozoan
      Planoprotostelium aurantium.
AB  - Developing unicellular fruiting bodies of the protostelid Planoprotostelium
      aurantium examined by electron microscopy are shown to have a cortical zone of
      microfilaments that surrounds the lower portion of the sporogenic cell and
      extends into a cytoplasmic plug that fills the lumen of the tubular,
      microfibrillar stalk. Labeling with the S-1 fragment of myosin indicates that the
      microfilaments are actin. A model is proposed in which the actin is involved both
      in a contractile process that serves to raise the sporogen off the substrate at
      the tip of the stalk and in a cytoskeletal role by either directly or indirectly
      localizing the synthesis and orientation of the stalk tube microfibrils. The
      process of culmination in protostelids is compared to that of the multicellular
      dictyostelid cellular slime molds.

PMID- 16592654
TI  - Darwin's finches: Population variation and sympatric speciation.
AB  - The classical model of the adaptive radiation of Darwin's finches is one of
      repeated speciation in allopatry. Evidence presented here suggests that sympatric
      specification may have contributed to the radiation. On Isla Genovesa Geospiza
      conirostris displays several features that are consistent with a model of
      sympatric speciation. Males are polymorphic in song type. Those singing song A
      have significantly longer bills than those singing song B. The two groups of
      males forage in different ways that are functionally associated with the bill
      differences, particularly in the nonbreeding season when food is probably
      limiting. Territories of mated song A and song B males alternate in space,
      whereas territories of unmated males do not. This suggests that females can
      discriminate between males on the basis of song and position, and the pattern is
      consistent with a hypothesis of assortative mating within song groups. The
      population is therefore polymorphic; the morphs occupy different niches in which
      they may be separately regulated and they could be on the way to achieving full
      reproductive isolation through assortive mating. It is suggested that the
      population may oscillate between fission and fusion tendencies due to a changing
      selection regime in this variable and unpredictable environment. There is no
      evidence that one of the morphs originated allopatrically and then immigrated to
      Genovesa. The possibility of sympatric speciation being partly responsible for
      the adaptive radiation, dismissed more than 30 years ago, should be reinstated.

PMID- 16592655
TI  - Heterogeneous flavonoid glucosyltransferases in purple derivatives from a
      controlling element-suppressed bronze mutant in maize.
AB  - The Ds(Dissociation)-suppressed bronze mutant bz-m2(DI), which is extremely
      stable in the absence of the regulatory element Ac (Activator), becomes both
      somatically and germinally unstable when Ac is present. Instability in the germ
      line may result in the generation of stable (Ac-nonresponding), colored Bz'
      derivatives. The characterization of several properties of the Bz-controlled
      enzyme UDPglucose: flavonoid 3-O-glucosyltransferase from mature kernel
      endosperms of 15 such Bz' derivatives has revealed two distinct groups. The
      enzyme in group I Bz' derivatives does not differ from the normal enzyme in the
      Bz progenitor allele of bz-m2(DI). Group II Bz' derivatives, on the other hand,
      make altered, labile UDPglucose:flavonoid glucosytransferases different from the
      normal enzyme and probably different from each other. The significance of these
      two classes of derivatives and possible mechanisms involved in their origin are
      discussed.

PMID- 16592656
TI  - Simultaneous hermaphroditism and sexual selection.
AB  - Theory about the evolution of sexual behavior in dioecious species is based on
      the general assumption that egg production is limited by a female's ability to
      garner resources to make eggs, not by a lack of sperm to fertilize them.
      Reproductive success for males is thus limited by access to females (and their
      eggs). I suggest that egg production by simultaneous hermaphrodites also obeys
      this principle-that fertilized egg production by an individual is not limited by
      sperm availability, but by resources allocated to eggs. If true, this suggests
      that sperm competition (reproduction success through male function) and a form of
      male-female conflict have played important roles in the evolution of
      hermaphroditism.

PMID- 16592657
TI  - Statistics of flexible chain configurations.
AB  - When Monte Carlo methods are employed to study the statistical dimensions of
      flexible polymer chains, it is necessary that the sampling be statistically
      unbiased. One Monte Carlo procedure is the so-called "slithering snake"
      technique, which has proved to be very useful. A question arises, however, as to
      how long it takes for a "slithering snake" to be completely regenerated to avoid
      biasing the samples around a particular configuration. It is demonstrated
      theoretically and verified by Monte Carlo studies that the number of iterations
      required to completely regenerate a sample polymer is a quadratic function of the
      chain length. This verification applies to chains in dilute solution but may not
      hold for bulk polymers.

PMID- 16592658
TI  - Multiple transitions induced by light intensity fluctuations in illuminated
      chemical systems.
AB  - The influence of external noise on the steady-state properties of a chemical
      system with very simple kinetics was studied. We dealt with an isomerization
      reaction, in a closed system, coupled to a light absorption and radiationless
      deexcitation process involving only one of the isomers. The theoretical analysis
      established that external noise deeply modified the macroscopic properties of the
      system and even induced transition phenomena that are totally unexpected from the
      usual deterministic description.

PMID- 16592659
TI  - Thermodynamic properties of solid CH(4).
AB  - The significant structures procedure of liquids has been used to calculate the
      thermodynamic properties of solid C(2)H(4). Two degeneracy terms were used to
      describe the behavior in the vicinities of the two phase transitions. The
      calculated entropy and specific heat agree well with experimental results from a
      few kelvins to the melting point. Less satisfactory agreement is obtained for
      compressibility and thermal expansion coefficients. This simple model represents
      surprisingly well the phase transitions in the solid state.

PMID- 16592660
TI  - Integrated spatial electron populations in molecules: The electron projection
      function.
AB  - A "projection function," P(x,z), is defined as the partial integral of the
      molecular electron density, rho(x,y,z), over the region -infinity < y <
      +infinity. The projection provides a three-dimensional representation of
      molecular electron distributions. Chemically useful information can be discerned
      from graphical displays in either perspective plot or contour format. Numerical
      integration of the function gives the integrated spatial electron population for
      any region of interest. The use of the projection function and difference
      functions is exemplified by application to acetaldehyde.

PMID- 16592661
TI  - Bedload transport associated with high stream power, Jordan River, Israel.
AB  - During a flood of a magnitude that recurs once in 100 years, boulders up to 1700
      mm in size were transported in the Jordan and Meshushim Rivers, northern Israel.
      Bedload discharge rates were estimated for periods of 3-72 hr of peak flow by a
      combination of hydrologic and geomorphic methods. Bedload transport rate is
      proportional to unit stream power in excess of that necessary for initial motion,
      raised to the power 3/2, as has been shown for data on other rivers.

PMID- 16592662
TI  - Oceanic warming of western Europe.
AB  - In the northern North Atlantic off Europe, deep convection flushes buoyancy and
      heat out of the upper ocean each winter. It is replaced by horizontal advection
      during the remainder of the year. Absolute geostrophic currents can be computed
      from an application of the heat conservation equation. A remarkable spiral with
      depth emerges as a key feature in the process. The computed field of flow appears
      to be consistent with several buoyancy and heat flux requirements, with the
      independent physical information of locally vanishing curl of the wind-stress,
      and with its implications through the Sverdrup relation.

PMID- 16592663
TI  - Local density functional theory of atoms and molecules.
AB  - A LOCAL DENSITY FUNCTIONAL THEORY OF THE GROUND ELECTRONIC STATES OF ATOMS AND
      MOLECULES IS GENERATED FROM THREE ASSUMPTIONS: (i) The energy functional is
      local. (ii) The chemical potential of a neutral atom is zero. (iii) The energy of
      a neutral atom of atomic number Z is -0.6127 Z(7/3). The energy functional is
      shown to have the form [Formula: see text] where A(0)=6.4563 and B(0)=1.0058. The
      first term represents the electronic kinetic energy, the second term represents
      the electron-electron repulsion energy for N electrons, and the third term is the
      nucleus-electron attraction energy. The energy E and the electron density rho are
      obtained and discussed in detail for atoms; their general properties are
      described for molecules. For any system the density becomes zero continuously at
      a finite distance from nuclei, and contours of the density are contours of the
      bare-nuclear potential v. For an atomic species of fractional charge q = 1 -
      (N/Z), an energy formula is obtained, [Formula: see text] which fits Hartree-Fock
      energies of 625 atoms and ions with root-mean-square error of 0.0270. A more
      general local density functional involving a coefficient B(N) = B(0)N(2/3) + B(1)
      is briefly considered.

PMID- 16592664
TI  - Nuclear gene iojap conditions a programmed change to ribosome-less plastids in
      Zea mays.
AB  - The recessive nuclear gene iojap of Zea mays conditions a permanent, heritable
      deficiency in the ability of the plastid to differentiate. iojap-affected
      plastids contain a normal genome as evidenced by comparison of the restriction
      endonuclease digestion patterns of affected and normal plastids. iojap-affected
      plastids contain neither detectable ribosomes nor high molecular weight RNA; the
      affected plastids do not incorporate exogenous amino acids into protein. The
      lesion in plastid ribosome content occurs early in organ ontogeny because iojap
      mediated albino stripes can occupy entire clones within affected leaves.

PMID- 16592665
TI  - Relation between senescence and stomatal opening: Senescence in darkness.
AB  - THE SENESCENCE (PROTEOLYSIS AND LOSS OF CHLOROPHYLL) OF ISOLATED LEAVES OF OAT
      SEEDLINGS IN THE DARK IS INHIBITED OR DELAYED BY COMPOUNDS OF SIX DIFFERENT
      TYPES: phenazine methosulfate, fusicoccin, alpha,alpha'-dipyridyl, cycloheximide,
      spermidine, and two cytokinins. In every case but the last, these compounds in
      optimum concentration caused the stomata to open and remain partly or completely
      open throughout the 72- or 96-hr experimental period. The cytokinins caused only
      a partial opening, which is ascribed to their exerting two different effects.
      Taken together with the previous report that five different treatments that
      accelerated or promoted senescence in the light caused stomatal closure or
      occlusion, these data establish a general parallel between stomatal aperture and
      senescence, with strong indication that the stomatal aperture is the causal
      factor. A possible explanation of the relationship is proposed.

PMID- 16592666
TI  - Disparity of gene conversion in frameshift mutants located in locus b2 of
      Ascobolus immersus.
AB  - The frequency of conversion and the disparity in the direction of conversion were
      studied for six frameshift mutants lying in locus b2 of Ascobolus immersus and
      giving more 2 wild type:6 mutant (2+6m) than 6 wild type:2 mutant (6+2m) aberrant
      asci (type B). The frequency of conversion decreased from left to right in the
      locus. The disparity steadily increased from left to right and then reached a
      plateau. Twenty-two frameshift mutants giving more 6+2m than 2+6m aberrant asci
      (type A) and closely linked to three type B mutants were also studied; they
      showed the same frequency of conversion and the same disparity (but in the
      opposite direction) as the type B mutant to which they are linked. The polar
      variation of both the frequency of conversion and the disparity as a function of
      position were expected on the basis of a previous study of 15 mutants giving
      postmeiotic segregations and located in locus b2. This variation is assumed to
      reflect the existence of a preferential region for the initiation of hybrid DNA
      (HDNA) during recombination and a duality in the distribution of this HDNA, with
      preponderant asymmetrical HDNA near the starting point and preponderant
      symmetrical HDNA farther from it.

PMID- 16592667
TI  - Pattern recognition in genetic sequences.
AB  - This paper announces an algorithm for finding pattern similarities between two
      given finite sequences. Two portions, one from each sequence, are similar if they
      are close in the metric space of evolutionary distances. In its most general form
      the algorithm allows a complete list to be made of all pairs of intervals, one
      from each of the two given sequences, such that each pair displays a maximum
      local degree of similarity; if the lengths of the sequences are m and n, then the
      algorithm requires on the order of mn steps. This result lends itself to
      detecting similarities by computer between pairs of biological sequences, such as
      proteins and nucleic acids.

PMID- 16592668
TI  - Density matrix method for orbital localization.
AB  - A method is presented for localizing molecular orbitals, based on diagonalizing
      subunits of the density matrix. First, nonbonding orbitals are found by
      diagonalizing the monatomic subunits; then, diatomic sigma or pi bonding and
      antibonding orbitals are obtained from the diatomic subunits for all bonded pairs
      of atoms; finally, the delocalized pi-orbitals for particular chromophores are
      found by projecting the first set out of the self-consistent field (SCF)
      Hamiltonian. The results show good general agreement with other localization
      methods, with advantages in the ability to display group orbitals in complex
      molecules which most closely resemble the SCF orbitals for simple prototypes.

PMID- 16592670
TI  - Determination of water mass properties of water pumped down from the Ekman layer
      to the geostrophic flow below.
AB  - In a subtropical gyre, the convergent Ekman layer forces water downward into the
      geostrophic flow below. The properties and depth of the mixed layer vary
      considerably during the course of the year, but this variability does not
      penetrate into the geostrophic region. Evidently there is some process at work
      that selects only late winter water for actual net downward pumping. It is a
      process much like that performed by Maxwell's Demon. Arguing from a particular
      example in a North Atlantic region where Sverdrup dynamics is presumed to
      prevail, an elementary description is given as to how the Demon works and a
      sample set of profiles by season is computed. Present day mixed layer models
      involve a local vertical mixing process. Thermocline theories involve adiabatic
      flow from high latitudes. There is an intermediate depth range at which the two
      processes operate alternatively, according to season.

PMID- 16592669
TI  - Time-resolved resonance Raman spectroscopy of intermediates of bacteriorhodopsin:
      The bK(590) intermediate.
AB  - We have combined microbeam and flow techniques with computer subtraction methods
      to obtain the resonance Raman spectrum of the short lived batho-intermediate
      (bK(590)) of bacteriorhodopsin. Comparison of the spectra obtained in (1)H(2)O
      and (2)H(2)O, as well as the fact that the bK(590) intermediate shows large
      optical red shifts, suggests that the Schiff base linkage of this intermediate is
      protonated. The fingerprint region of the spectrum of bK(590), sensitive to the
      isomeric configuration of the retinal chromophore, does not resemble the
      corresponding region of the parent bR(570) form. The resonance Raman spectrum of
      bK(590) as well as the spectra of all of the other main intermediates in the
      photoreaction cycle of bacteriorhodopsin are discussed and compared with
      resonance Raman spectra of published model compounds.

PMID- 16592671
TI  - Neodymium isotopes in flood basalts from the Siberian Platform and inferences
      about their mantle sources.
AB  - The initial isotopic compositions of Nd and Sr in basalts from the Central
      Siberian Plateau and other major continental flood basalts are reported. The
      continental flood basalts appear to be the product of partial melting of mantle
      sources that consist of relatively primitive undifferentiated material and are
      clearly distinct from midocean ridge basalts, which sample mantle reservoirs that
      have been modified by extraction of continental crust earlier in earth history.
      These observations provide fundamental constraints on models of mantle structure
      and dynamics. Isotopic effects of crustal contamination are clearly recognizable
      in some continental flood basalts, but these effects can be distinguished from
      isotopic patterns inherited from the mantle magma sources.

PMID- 16592672
TI  - An L form of Bernstein's inequality.
AB  - Suppose P is a pth degree real polynomial function in n variables and f=PS(n-1)
      is the restriction of P to the unit sphere S(n-1) in R(n). Bernstein's inequality
      asserts that ([unk](0) (k)f)(2) + p(2)([unk](0) (k-1)f)(2) </= p(2k) parallelf
      parallelinfinity(2), where k >/= 1 and differentiation is with respect to arc
      length theta along any geodesic in S(n-1). We find the constant corresponding to
      p(2k) when parallelf parallelinfinity is replaced by parallelf parallel(2). One
      application is a condition on the coefficients of the expansion in surface
      spherical harmonics of any g: S(n-1) --> R, which condition suffices to assure
      that g is k times differentiable.

PMID- 16592673
TI  - Local convergence theorems for adaptive stochastic approximation schemes.
AB  - For the regression model y = M(x) + epsilon, adaptive stochastic approximation
      schemes of the form x(n+1) = x(n) - y(n)/(nb(n)) for choosing the levels
      x(1),x(2),... at which y(1),y(2),... are observed converge with probability 1 to
      the unknown root theta of the regression function M(x). Certain local convergence
      theorems that relate the convergence rate of x(n) - theta to the limiting
      behavior of the random variables b(n) are established.

PMID- 16592674
TI  - Separation and structure of the prosthetic group of the blue fluorescence protein
      from the bioluminescent bacterium Photobacterium phosphoreum.
AB  - The highly fluorescent prosthetic group of the blue fluorescence protein purified
      from the bioluminescent bacterium Photobacterium phosphoreum has been dissociated
      and separated from its apoprotein by affinity chromatography on Cibacron Blue
      Sepharose. It has been identified as 6,7-dimethyl-8-(1'-D-ribityl)lumazine by
      several methods of characterization, all of which gave results identical to those
      for an authentic sample. In neutral solution, absorption maxima are at 407, 275
      (shoulder), and 256 nm, with a single fluorescence maximum at 491 nm. The proton
      magnetic resonance spectrum exhibits a singlet at 2.66 ppm corresponding to the
      methyl substituted at the 6 position of lumazine and a multiplet centered at 3.85
      ppm corresponding to the C-2'-5' protons of the ribityl group. A Raman spectrum
      was obtained by the technique of coherent anti-Stokes Raman scattering and the
      R(F) values by paper chromatography were determined in four solvent systems. The
      isolated compound was readily transformed into riboflavin by riboflavin
      synthetase. Fifty grams (dry weight) of P. phosphoreum contains at least 20 mg of
      this lumazine derivative, an amount comparable to that found in other
      microorganisms classified as riboflavin overproducers. The overproduction of this
      lumazine in this case apparently has to do with its function in the generation of
      bioluminescence.

PMID- 16592675
TI  - Sites of intermolecular crosslinking of fatty acyl chains in phospholipids
      carrying a photoactivable carbene precursor.
AB  - Sonicated vesicles of 1-fatty acyl-2-omega-(2-diazo-3,3,3-trifluoropropionoxy)
      fatty acyl sn-glycero-3-phosphoryl-cholines were shown recently to form
      intermolecular crosslinks by insertion of the photogenerated carbene into a C-H
      bond of a neighboring hydrocarbon chain. We now report that photolysis of
      multilamellar dispersions gives a second series of products in which carbene
      insertion is accompanied by elimination of a molecule of hydrogen fluoride. The
      sites of crosslinking in the latter compounds have been studied by mass
      spectrometry using phospholipids with varying chain lengths of the fatty acyl
      groups carrying the carbene precursor. The patterns observed show that the point
      of maximum crosslinking is consistent with the recent conclusion that in
      phospholipids the sn-2 fatty acyl chain trails the sn-1 chain by 2-4 atoms.

PMID- 16592676
TI  - Favin versus concanavalin A: Circularly permuted amino acid sequences.
AB  - We have determined the tentative amino acid sequence of the beta chain (M(r)
      20,000) of the lectin favin. In previous studies, we have shown that the alpha
      chain (M(r) 5600) of this lectin is homologous to a region in the middle of the
      concanavalin A (Con A) sequence (residues 70-119). Now we present evidence that
      the beta chain is homologous to two discrete segments of Con A. The homology
      begins at residue 120 of Con A, extends to the COOH terminus (residue 237) and
      continues without interruption through the NH(2)-terminal 69 residues of Con A.
      Together, the alpha and beta chains of favin account for a polypeptide chain
      equivalent in size to that of Con A. The comparison of the two proteins thus
      reveals a circular permutation of extensive homologous sequences. The favin
      molecule contains residues identical to many of the residues postulated to be
      involved in sugar binding by Con A, and contains all of the direct metal ligands
      as well as residues homologous to most of the residues that form the beta-pleated
      sheets of Con A. These homologies suggest that the three-dimensional structures
      of the two lectins are likely to be very similar. Moreover, favin appears to be
      even more closely related in primary structure and sugar specificity to the
      lectins from pea and lentil, raising the possibility that all of these lectins
      may have structures that resemble Con A. Some of these similarities may also
      extend to the lectins from soybean, peanut, and red kidney bean, which have
      different sugar specificities but share sequence homologies with the favin beta
      chain.

PMID- 16592677
TI  - Hydrostatic pressure in small phospholipid vesicles.
AB  - The internal solvent-filled cavity of a singlewalled spherical phospholipid
      vesicle must be at essentially the same pressure as the aqueous medium outside
      the vesicle. Whether or not the bilayer itself is under elevated pressure cannot
      at present be determined.

PMID- 16592678
TI  - Pollen-stigma interactions: Identification and characterization of surface
      components with recognition potential.
AB  - Male-female recognition in flowering plants is initiated by mutual contact of
      pollen and stigma surface components. Analysis of the surface macromolecules of
      both stigma and pollen of Gladiolus gandavensis revealed a complex mixture of
      proteins, glycoproteins, and glycolipids. The carbohydrate-containing components
      amounted to 6% in pollen and 23% in stigma and contained the monosaccharides
      galactose, arabinose, glucose, mannose, and rhamnose. All the mannose of both
      preparations was associated with a fraction that bound to concanavalin A. The
      stigma surface contained an arabinogalactan or arabinogalactan protein as a major
      component. This component has been isolated by affinity chromatography on
      tridacnin-Sepharose and shown to be similar in composition to a style canal
      component isolated in the same way. The capacity of the stigma surface
      preparations to bind nonspecifically to macromolecules from pollen and other
      sources has been demonstrated in vivo and in vitro. Specific binding of
      concanavalin A to the stigma surface decreases the adhesive capacity for pollen
      protein. The arabinogalactan of the stigma surface may act as an adhesive base.
      The pollen and stigma surfaces apparently complement one another to provide all
      the components of an ideal adhesive.

PMID- 16592679
TI  - Iron-dextran antibody conjugates: General method for simultaneous staining of two
      components in high-resolution immunoelectron microscopy.
AB  - We report the preparation and properties of an electron-dense antibody conjugate,
      made by the covalent bonding of an iron-dextran (Imposil) particle to an antibody
      molecule. Transmission electron microscopic experiments with the Imposil-antibody
      conjugates demonstrate their suitability as specific immunostains at high
      resolution, particularly for simultaneous double staining experiments in
      conjunction with ferritin-antibody conjugates.

PMID- 16592680
TI  - Interior remodeling of the shell by a gastropod mollusc.
AB  - As the Conus shell grows by spiraling of the outer lip around the axis, profound
      internal shell dissolution thins the walls of the protected penultimate whorl
      from several millimeters to <50mum. Shell material is added to the inside of the
      spire and the anterior part of the columella. The resulting shell has a uniformly
      thick last whorl and thickened spire that enhance defense against crushing
      predators and a greatly expanded interior living space for the animal.

PMID- 16592681
TI  - Healing of mat mutations and control of mating type interconversion by the mating
      type locus in Saccharomyces cerevisiae.
AB  - Homothallic yeasts switch cell types (mating types a and alpha) at high frequency
      by changing the alleles of the mating type locus, MATa and MATalpha. We have
      proposed in the cassette model that yeast cells contain silent MATa and MATalpha
      blocs ("cassettes"), copies of which can be substituted at the mating type locus
      for the resident information. The existence of silent cassettes was originally
      proposed to explain efficient switching of a defective MATalpha locus (matalpha)
      to a functional MATalpha locus. We report here that this "healing" of mat
      mutations is a general property of the mating type interconversion system and is
      not specific to the class of matalpha mutations studied earlier: a defective MATa
      (mata1) switches readily to MATa and various matalpha loci switch readily to
      MATalpha. These observations satisfy the prediction of the cassette model that
      all mutations within MATa and MATalpha be healed. These studies also identify MAT
      functions that control the switching process: the same functions known to promote
      sporulation and prevent mating in a/alpha cells also inhibit the switching system
      in a/alpha cells. Finally, we present additional characterization of a natural
      variant of MATalpha, MATalpha-inc [Takano, I., Kusumi, T. & Oshima, Y. (1973)
      Mol. Gen. Genet. 126, 19-28] that is insensitive to switching. Our observation
      that MATalpha-inc acts in cis suggests that it may be altered in a site concerned
      with excision of MATalpha-inc or its replacement by another cassette.

PMID- 16592682
TI  - Conditioned responses in courtship behavior of normal and mutant Drosophila.
AB  - Male courtship behaviour in Drosophila melanogaster is modified by prior sexual
      experience. Whereas naive males nearly always court virgin females persistently,
      males previously paired with unreceptive fertilized females subsequently court
      virgin females in an abbreviated manner, if at all. The probability of diminished
      male courtship is directly related to the duration of the prior "conditioning"
      period with a fertilized female. Naive males court fertilized females less
      vigorously than they court virgins; this depression of male behavior occurs even
      if the male is blind or if the fertilized female cannot actively reject his
      courtship. These results suggest that fertilized females are a source of both
      courtship-provoking and courtship-inhibiting olfactory cues and that the central
      association of these cues in males is sufficient to bring about the retention of
      modified courtship behavior. Mutant "amnesiac" males, selected as memory
      deficient in a learning test unrelated to courtship [Quinn, W. G., Sziber, P. P.
      & Booker, R. (1979) Nature (London) 277, 212-214], are trainable by exposure to
      fertilized females, but the experience-dependent behavior-diminished courtship
      performance-wanes abnormally rapidly-i.e., less than 1 hour, compared to 2-3 hr
      for wild-type flies.

PMID- 16592683
TI  - A pseudoduplication in Lycopersicon pimpinellifolium.
AB  - A double-banded variant of Prx-2 encountered in a single wild plant in a previous
      survey of the peroxidases of Lycopersicon pimpinellifolium was subjected to
      genetic analysis. Segregations obtained from crosses of this true-breeding type
      with various alleles of Prx-2 yielded anomalous segregations that are not
      compatible with a single locus model and suggest activity of alleles of a gene at
      another, independent locus. A critical test was afforded by studying simultaneous
      segregation for the apparent duplication and for two alleles at the neighboring
      Prx-3, a gene which proves to be very tightly linked with Prx-2. The results of
      the new test revealed independence between the double-banded type and Prx-3,
      hence also between the former and Prx-2. The most tenable hypothesis stipulates
      that an independent gene mPx2(1) modifies post-translationally the product coded
      by Prx-2(+) to yield two electrophoretically separable isozymes. These results
      reveal the risk of assuming, without appropriate genetic tests, that gene
      duplication is necessarily the cause of multiple banding.

PMID- 16592684
TI  - Model of effectively neutral mutations in which selective constraint is
      incorporated.
AB  - Based on the idea that selective neutrality is the limit when the selective
      disadvantage becomes indefinitely small, a model of neutral (and nearly neutral)
      mutations is proposed that assumes that the selection coefficient (s') against
      the mutant at various sites within a cistron (gene) follows a Gamma distribution;
      f(s') = alpha(beta)e(-alphas')s'(beta-1)/Gamma(beta), in which alpha = beta/ s'
      and s' is the mean selection coefficient against the mutants ( s' > 0; 1 [unk]
      beta > 0). The mutation rate for alleles whose selection coefficients s' lie in
      the range between 0 and 1/(2N(e)), in which N(e) is the effective population
      size, is termed the effectively neutral mutation rate (denoted by v(e)). Using
      the model of "infinite sites" in population genetics, formulas are derived giving
      the average heterozygosity ( h(e)) and evolutionary rate per generation (k(g)) in
      terms of mutant substitutions. It is shown that, with parameter values such as
      beta = 0.5 and s' = 0.001, the average heterozygosity increases much more slowly
      as N(e) increases, compared with the case in which a constant fraction of
      mutations are neutral. Furthermore, the rate of evolution per year (k(1)) becomes
      constant among various organisms, if the generation span (g) in years is
      inversely proportional to radicalN(e) among them and if the mutation rate per
      generation is constant. Also, it is shown that we have roughly k(g) = v(e). The
      situation becomes quite different if slightly advantageous mutations occur at a
      constant rate independent of environmental conditions. In this case, the
      evolutionary rate can become enormously higher in a species with a very large
      population size than in a species with a small population size, contrary to the
      observed pattern of evolution at the molecular level.

PMID- 16592685
TI  - Equivalence of maximizing reproductive value and fitness in the case of
      reproductive strategies.
AB  - The proposed equivalence of maximizing reproductive value and fitness is examined
      for two model life histories. In the first instance, it is assumed that offspring
      are fledged before the start of the next breeding season. In this case the
      proposed equivalence is verified. In the second model, parents care for their
      progeny for more than 1 year. In this case the optimal reproductive expenditure
      at a particular age is shown to depend on both current reproductive value and the
      diminution in survival rates of previously conceived young still dependent on
      parental protection.

PMID- 16592686
TI  - Effect of molecular rotation on the vibration-vibration energy transfer in
      condensed media.
AB  - The purpose of the present communication has been to present the derivation of
      the vibrational relaxation rate constant for the case in which both phonons and
      the molecular rotation (three-dimensional) participate in the vibrational
      relaxation and to study the effect of molecular rotation on the vibration
      vibration energy transfer in the condensed phase. The experimental results of
      vibration-vibration energy transfer between donors, NH and ND, and acceptors, CO
      and (13)CO, have been analyzed.

PMID- 16592687
TI  - Brasilenyne and cis-dihydrorhodophytin: Antifeedant medium-ring haloethers from a
      sea hare (Aplysia brasiliana).
AB  - Two straight-chain C(15) fish antifeedants have been isolated from the sea hare
      Aplysia brasiliana. Chemical, spectral, and x-ray diffraction studies led to the
      characterization of these medium-ring ethers as brasilenyne (2) and cis
      dihydrorhodophytin (3). The oxonin ring system of 2 is novel in nature.
      Biosynthetic considerations permit the postulation that a third compound, a
      noncrystalline congener of these compounds, is cis-isodihydrohodophytin (4).

PMID- 16592688
TI  - Models of earth structure inferred from neodymium and strontium isotopic
      abundances.
AB  - A simplified model of earth structure based on the Nd and Sr isotopic
      characteristics of oceanic and continental tholeiitic flood basalts is presented,
      taking into account the motion of crustal plates and a chemical balance for trace
      elements. The resulting structure that is inferred consists of a lower mantle
      that is still essentially undifferentiated, overlain by an upper mantle that is
      the residue of the original source from which the continents were derived.

PMID- 16592689
TI  - Characterization of parallel subtraction.
AB  - Parallel subtraction is an operation defined on pairs of positive operators. In
      terms of electrical networks, one may pose the following problem: Given an
      electrical network, represented by a specified positive operator, determine the
      set of positive operators which when connected in parallel with the specified
      operator yield another prescribed operator. The set of solutions of this
      electrical network problem is shown to have a minimum. The minimum is termed "the
      parallel difference of the fixed operators," and the operation is termed
      "parallel subtraction." The parallel difference is used to obtain explicit error
      estimates for an iteration procedure which approximates the geometric mean of
      positive operators. This concept of the geometric mean reduces to the square root
      of the product of the operators if the operators commute. Finally, by using the
      geometric mean, an operator version of the Gaussian mean is presented.

PMID- 16592690
TI  - The zero dispersion limit for the Korteweg-deVries KdV equation.
AB  - We use the inverse scattering method to determine the weak limit of solutions of
      the Korteweg-deVries equation as dispersion tends to zero. The limit, valid for
      all time, is characterized in terms of a quadratic programming problem which can
      be solved with the aid of function theoretic methods. For large t, the solutions
      satisfy Whitham's averaged equations at some times and the equations found by
      Flaschka et al. at other times.

PMID- 16592691
TI  - From deterministic dynamics to probabilistic descriptions.
AB  - THE PRESENT WORK IS DEVOTED TO THE FOLLOWING QUESTION: What is the relationship
      between the deterministic laws of dynamics and probabilistic description of
      physical processes? It is generally accepted that probabilistic processes can
      arise from deterministic dynamics only through a process of "coarse graining" or
      "contraction of description" that inevitably involves a loss of information. In
      this work we present an alternative point of view toward the relationship between
      deterministic dynamics and probabilistic descriptions. Speaking in general terms,
      we demonstrate the possibility of obtaining (stochastic) Markov processes from
      deterministic dynamics simply through a "change of representation" that involves
      no loss of information provided the dynamical system under consideration has a
      suitably high degree of instability of motion. The fundamental implications of
      this finding for statistical mechanics and other areas of physics are discussed.
      From a mathematical point of view, the theory we present is a theory of
      invertible, positivity-preserving, and necessarily nonunitary similarity
      transformations that convert the unitary groups associated with deterministic
      dynamics to contraction semigroups associated with stochastic Markov processes.
      We explicitly construct such similarity transformations for the so-called
      Bernoulli systems. This construction illustrates also the construction of the so
      called Lyapounov variables and the operator of "internal time," which play an
      important role in our approach to the problem of irreversibility. The theory we
      present can also be viewed as a theory of entropy-increasing evolutions and their
      relationship to deterministic dynamics.

PMID- 16592692
TI  - Characterization of double-stranded ribonucleic acid in tobacco leaves.
AB  - Double-stranded RNA was isolated from tobacco leaves and characterized in terms
      of base composition, density, and nuclease resistance. Although its role in the
      plant's physiology is not clear, evidence was adduced that it is the product of
      the RNA-dependent RNA polymerase previously shown to occur in this and other
      plants. The fact that twice as much fully than partially double-stranded RNA
      appears to be made favors a regulatory role for the double-stranded RNA rather
      than a transcriptional intermediate role.

PMID- 16592693
TI  - Ratio of tree branch lengths: The equitable distribution of leaf clusters on
      branches.
AB  - The theoretical optimal ratios of branch lengths, which produce the most
      equitable distribution (minimum deviation) of leaf clusters in a computer
      stimulated branch system, are similar to the observed ratios in real trees of
      Terminalia. In another study, observed values for branch angles in this species
      were shown to be similar to theoretical optimal values that produce the maximum
      effective leaf area. The relationship between these two fundamental parameters of
      bifurcation and tree geometry and their effect on effective leaf area and
      distribution of leaves are discussed.

PMID- 16592694
TI  - Induction of cytokinin autonomy by N,N'-diphenylurea in tissue cultures of
      Phaseolus lunatus L.
AB  - The ability of N,N'-diphenylurea (Ph(2)urea) to substitute for cytokinin-active
      adenine derivatives in promoting callus growth of Phaseolus lunatus has been
      examined. In general, Ph(2)urea stimulated callus growth at high concentrations,
      although the growth of most callus tissues was irregular. Variability in the
      sensitivity and uniformity of the growth response to Ph(2)urea was found among
      different genotypes of P. lunatus. Most importantly, tissues cultured on
      Ph(2)urea-containing medium for one passage had acquired the ability to
      proliferate in subsequent passages in the absence of either Ph(2)urea or
      cytokinin-active adenine derivatives. Corresponding tissues maintained on kinetin
      containing medium remained cytokinin-dependent. It appears that the effect of
      Ph(2)urea in promoting the growth of P. lunatus callus tissue resides in its
      ability to induce cytokinin autonomy. This result suggests that the cytokinin
      activity of Ph(2)urea may be due to promotion of endogenous cytokinin
      biosynthesis in the bioassay systems in which it is active.

PMID- 16592695
TI  - Further examination of presumptive Rhizobium trifolii mutants that nodulate
      Glycine max.
AB  - Two recent reports described the isolation of derivatives of a Rhizobium trifolii
      strain that had gained the ability to nodulate Glycine max and Vigna radiata and
      that had demonstrated altered patterns of carbon source utilization, free-living
      nitrogen fixation, and hydrogen uptake. More extensive characterization of these
      strains now supports the conclusion that these strains are R. japonicum and are
      not derived from the putative parent R. trifolii.

PMID- 16592696
TI  - Bed load transport by submerged jets.
AB  - Some similarities are presented between the bed load transport of noncohesive
      grains in long rivers and at a local, jet-induced scour. Experiments are
      described in which a submerged two-dimensional slot nozzle, inclined downward,
      eroded a deep sand bed. The rate of erosion at the very beginning of a scour was
      evaluated and compared with river data by use of the idea of "stream-power."
      Empirical relationships for the two cases are similar, although the geometry of
      the boundaries is quite different.

PMID- 16592697
TI  - A theory of light-induced explosion.
AB  - This paper presents a theoretical analysis, based on a simplified one-dimensional
      model, of the response of an explosive to a wide range of light intensities. A
      primary result has been the identification and development of a relationship
      among the important critical parameters. Numerical results illustrating the
      relationship among the critical light intensity, sample dimension, and ambient
      temperature have been obtained, with lead azide as the example.

PMID- 16592698
TI  - Ligated chlorophyll cation radicals: Their function in photosystem II of plant
      photosynthesis.
AB  - Magnesium tetraphenylchlorin, a synthetic model for chlorophyll, exhibits
      significant variations in the unpaired spin densities of its cation radicals with
      concomitant changes in oxidation potentials as a function of solvent and axial
      ligand. Similar effects are observed for chlorophyll (Chl) a and its cation
      radicals. Oxidation potentials for Chl --> Chl(+.) as high as +0.9 V (against a
      normal hydrogen electrode) are observed in nonaqueous solvents, with linewidths
      of the electron spin resonance signals of monomeric Chl(+.) ranging between 9.2
      and 7.8 G in solution. These changes in electronic configuration and ease of
      oxidation are attributed to mixing of two nearly degenerate ground states of the
      radicals theoretically predicted by molecular orbital calculations. Comparison of
      the properties of chlorophyll in vitro with the optical, redox, and magnetic
      characteristics attributed to P-680, the primary donor of photosystem II which
      mediates oxygen evolution in plant photosynthesis, leads us to suggest that P-680
      may be a ligated chlorophyll monomer whose function as a phototrap is determined
      by interactions with its (protein?) environment.

PMID- 16592699
TI  - Interfacial free energy and the hydrophobic effect.
AB  - Interfacial free energies demonstrate clearly that the antipathy between
      hydrocarbon and water rests on the strong attraction of water for itself.
      However, the unfavorable free energy associated with this antipathy, per unit
      area of contact between bulk hydrocarbon and water, is about 3-fold larger than a
      similar figure derived from solubility data per unit area of contact between a
      single dissolved hydrocarbon molecule and water. The discrepancy illustrates the
      difficulty in applying macroscopic concepts such as "interfacial surface" at the
      molecular level and can be formally resolved, at least qualitatively, by the
      predicted effect of surface curvature on surface tension.

PMID- 16592700
TI  - On spin-exchange and electron-transfer rates in bacterial photosynthesis.
AB  - A discrepancy is explored regarding the spin exchange integral estimated from
      magnetic field effects on recombination of the bacteriochlorophyll dimer cation
      (Bchl)(2)+ and the bacteriopheophytin anion Bph(-) and the measured electron
      transfer rate between Bph and electronically excited (Bchl)(2). In one
      explanation considered here there are two sites for the electron or for the hole,
      with a hopping between sites.

PMID- 16592701
TI  - Earth science and earth resources-A centenary salute to the U.S. Geological
      Survey: Introduction to the symposium.

PMID- 16592702
TI  - Role of the U.S. Geological Survey in federal and national science.

PMID- 16592703
TI  - Structural geology of the Earth's interior.
AB  - Seismology is providing a more sharply focused picture of the Earth's internal
      structure that should lead to improved models of mantle dynamics. Lateral
      variations in seismic wave speeds have been documented in all major layers of the
      Earth external to its core, with horizontal scale lengths ranging from 10 to
      10(4) km. These variations can be described in terms of three types of
      heterogeneity: compositional, aeolotropic, and thermobaric. All three types are
      represented in the lithosphere, but the properties of the deeper inhomogeneities
      remain hypothetical. It is argued that sublithospheric continental root
      structures are likely to involve compositional as well as thermobaric
      heterogeneities. The high-velocity anomalies characteristic of subduction zones
      seismic evidence for detached and sinking thermal boundary layers-in some areas
      appear to extend below the seismicity cutoff and into the lower mantle or
      mesosphere. Mass exchange between the upper and lower mantles is implied, but the
      magnitude of the flux relative to the total mass flux involved in plate
      circulations is as yet unknown. Other observations, such as the vertical travel
      time anomalies seen in the western Pacific, may yield additional constraints on
      the flow geometries, but further documentation is necessary. Thermobaric
      heterogeneities associated with a thermal boundary layer at the base of the
      mantle could provide the explanation for some of the observations of
      heterogeneities in the deep mantle. The evidence for very small scale
      inhomogeneities (<50 km) in region D'' and for topography on the core-mantle
      interface motivate the speculation that there is a chemical boundary layer at
      this interface, as well as a thermal one.

PMID- 16592704
TI  - Structural geology of the Earth's exterior.
AB  - Plate tectonics offers an explanation for the present motions and heterogeneity
      of the rocks that form the external part of the Earth. It explains the origin of
      the first-order heterogeneity of oceanic and continental lithospheres.
      Furthermore, it explains the youth and simplicity of the oceanic lithosphere and
      offers the potential to explain the antiquity, complexity, and evolution of the
      continental lithosphere. The framework of plate tectonics must be used carefully,
      because there are geological features within continents, particularly in the more
      ancient rocks, that may require alternative explanations. The task of
      understanding lithospheric motions through geologic time must be focused on the
      continents, where the major evidence for 95% of Earth history resides.IN
      INTERPRETING EARTH MOTIONS FROM THE GEOLOGIC RECORD, THREE NEEDS SEEM PARAMOUNT:
      (i) to develop a three-dimensional understanding of the kinematics, dynamics, and
      thermal structure of modern plate boundary systems and at the same time to
      recognize those geological and geophysical features that are unrelated to plate
      interaction; (ii) to use this understanding to reconstruct the extent and
      evolution of ancient systems that form the major elements of continental crust;
      and (iii) to determine the dynamics and evolution of systems that have no modern
      analogs. Decoupling along subhorizontal zones within the lithosphere may be
      widespread in all types of plate boundary systems. Thus, in order to interpret
      the motion and dynamics of the mantle correctly, it is important to know if upper
      lithospheric motion within boundary systems is controlled directly or indirectly
      by or is independent of deeper mantle motions.

PMID- 16592705
TI  - Earth history at the century mark of the U.S. Geological Survey.
AB  - Earth history involves all aspects of geological and biological evolution,
      especially paleontology and stratigraphy. Early paleontological exploration of
      the western United States by and before the U.S. Geological Survey featured the
      dramatic discoveries and rivalries of the great vertebrate paleontologists Leidy,
      Cope, Marsh, and Osborn. Invertebrate paleontology and paleobotany in the U.S.
      Geological Survey blossomed with emphasis on practical missions. The most
      illuminating and useful earth history, nevertheless, emerges where there is a
      high degree of interaction with academic scholars. Despite a good knowledge of
      its broad features, the drama of earth history remains obscure in detail. Whereas
      it speaks conclusively for the reality of organic evolution, it is less
      conclusive about mechanisms and many important transitions. Current
      investigations, however, especially in pre-Phanerozoic, mammalian, and human
      paleontology, promise improved insights. New techniques in collecting, sample
      preparation, and research are revealing previously unknown kinds of fossils and
      exquisite details of preservation. Plate tectonic theory provides a new framework
      for historical geography and biogeography. Emerging techniques in geochronology
      matching paleopolarity sequences, for example-promise to resolve old problems of
      the synchroneity or heterochroneity of different biotal provinces. As it splits
      into subfields, the teaching and practice of paleontology expand to cover all of
      them. The fossils themselves, however, remain the basic objective evidence. All
      hypotheses about them must answer to this court of appeal. But nature rarely
      responds in an either-or way. The most probable hypotheses are those that have
      repeatedly confronted objective reality and survived all opportunity for
      disproof.

PMID- 16592706
TI  - Earth resources.
AB  - Reliable supplies of metals have historically been the keys to industrial and
      technological development. But many metals are subject to the possible exhaustion
      of traditional kinds of deposits. A continued supply of such metals, which
      include tin, tungsten, silver, lead, zinc, and many others, will require their
      recovery from common rocks, in which they are found in solid solution in common
      silicate minerals. Recovery from unconventional sources will be so energy
      intensive that we may eventually have to stop mining such metals. The greatest
      challenge facing the U.S. Geological Survey in its second century will be the
      problem of resource limitations.

PMID- 16592707
TI  - The homogeneity conjecture.
AB  - We show that, for any function f in which Kleene's O is computable, the ordering
      of Turning degrees (i.e., degrees of difficulty of computation of functions) is
      not isomorphic to the ordering of degrees of functions from which f is
      computable. This refutes a well-known conjecture of H. Rogers, Jr., and others.

PMID- 16592708
TI  - Organelle DNA variation and systematic relationships in the genus Zea: Teosinte.
AB  - Chloroplast and mitochondrial DNAs from six races of annual teosinte (Guatemala,
      Huehuetenango, Balsas, Central Plateau, Chalco, and Nobogame), perennial
      teosinte, and maize were compared and grouped by restriction endonuclease
      fragment analyses. Three groups of chloroplast DNAs were detected: (i) perennial
      teosinte and Guatemala; (ii) Balsas and Huehuetenango; and (iii) all other
      teosintes. Four groups of mitochondrial DNAs were separated: (i) perennial
      teosinte; (ii) Guatemala; (iii) Nobogame; and (iv) all other teosintes.
      Separation of the teosinte and maize organelle DNAs into five groups (Guatemala;
      perennial teosinte; Balsas and Huehuetenango; Central Plateau and Chalco;
      Nobogame and maize) approximated the biosystematic relationships of the taxa. It
      was suggested that the evolutions of the chloroplast and mitochondrial DNAs may
      be independent of each other, that variation of organelle DNA within a species
      complex of an organism may be the common condition, and that the DNAs of the
      organelle and nuclear systems evolve in reasonable harmony.

PMID- 16592709
TI  - Cytoplasmic phase separation in formation of galactosemic cataract in lenses of
      young rats.
AB  - We have determined the age dependence of the characteristics of the cytoplasmic
      phase separation of lenses from normal and galactosemic young rats. In the normal
      lens, the temperature at which the phase separation occurs decreases
      monotonically with age. In the lenses of rats fed with a high galactose diet, the
      phase separation temperature becomes increasingly higher with the development of
      galactosemia. When the phase separation temperature becomes higher than the
      ocular temperature, the nuclear opacity appears in vivo. The opacity is the
      result of light scattering by spatial fluctuations of the refractive index formed
      by interspersed regions of two separated phases in the fiber cell cytoplasm. This
      shows that the nuclear opacity that develops in the lens of galactosemic rats is
      the manifestation of phase separation of the lens fiber cytoplasm.

PMID- 16592710
TI  - Photooxidation of the high-potential iron-sulfur center in chloroplasts.
AB  - The high-potential iron-sulfur center associated with the g = 1.89-1.90 electron
      paramagnetic resonance signal in spinach chloroplasts is fully reduced in the
      dark. It is photooxidized in the presence of 3-(3,4-dichlorophenyl)-1,1
      dimethylurea and reduced after illumination with red actinic light in the absence
      of inhibitors. The light-induced redox changes of the high-potential iron-sulfur
      center are shown to correlate with those of plastocyanin detected at g = 2.05.
      Demonstration of light-induced redox changes in the high-potential iron-sulfur
      center provides support for a functional role of this component in the
      chloroplast electron transport chain.

PMID- 16592711
TI  - Experimental hybridization of Coelomomyces dodgei and Coelomomyces punctatus.
AB  - Two closely related fungi, Coelomomyces dodgei and C. punctatus
      (Chytridiomycetes; Blastocladiales), showing considerable potential for mosquito
      control, have been hybridized. Both species have life cycles involving an
      obligate alteration of sexual and asexual generations between an intermediate
      copepod host and a definitive mosquito host, respectively. Hybridization was
      accomplished by making reciprocal crosses of gametes derived from infected
      copepods. In both cases, C. dodgei [unk] x C. punctatus [unk] and C. punctatus
      [unk] x C. dodgei [unk], zygotes infective for mosquito larvae were formed. Most
      sporangia produced by the hybrids in infected larvae were not typical of either
      parental species but resembled C. dodgei more than C. punctatus. Additionally,
      the majority of the sporangia formed in several larvae exhibited surface
      structures similar to C. lativittatus, indicating this species may be a naturally
      occurring hybrid of C. dodgei and C. punctatus. The experimental methods
      described provide a system to aid in the study of taxonomic relationships among
      closely related species of Coelomomyces, and furthermore they may contribute to
      the development of strains efficacious for mosquito control.

PMID- 16592712
TI  - Photooxidation of antenna bacteriochlorophyll in chromatophores from
      carotenoidless mutant Rhodopseudomonas sphaeroides and the attendant loss of
      dimeric exciton interaction.
AB  - Intense continuous illumination of purified chromatophores from carotenoidless
      mutant Rhodopseudomonas sphaeroides results in progressive photooxidative loss of
      the near infrared absorption band near 860 nm assigned to antenna
      bacteriochlorophyll. The quantum yield of this reaction is low, approximately 1.7
      x 10(-5). The loss in near infrared absorption is accompanied by a proportional
      shift in the absorption maximum to shorter wavelengths. The double circular
      dichroism feature in the near infrared decreases at a faster rate than does the
      absorbance. These results are explained by a model in which the antenna
      bacteriochlorophyll, initially associated as dimers (lambda(max) = 860.2 nm), is
      progressively converted to the monomeric state (lambda(max) = 851.9 nm). The
      wavelength shift is attributed to disruption of exciton coupling in the dimer.
      Acetone/methanol extraction indicates that the maximum molar extinction
      coefficients of the dimer and monomer do not differ by more than 4%. The
      occurrence of an absorption maximum at 852 nm for monomeric bacteriochlorophyll
      in a protein complex demonstrates that it is not necessary to invoke aggregation
      of the chromophores as the origin of the shift from 770 nm in typical organic
      solvents.

PMID- 16592713
TI  - Race-specific molecules that protect soybeans from Phytophthora megasperma var.
      sojae.
AB  - Phytophthora megasperma var. sojae (A. A. Hildebrand) is a fungal stem and root
      rot-causing pathogen of soybeans. Glycoproteins secreted into the medium of the
      aseptically cultured fungus have been partially purified by (NH(4))(2)SO(4)
      precipitation and by column chromatography on norleucine-substituted Sepharose 4B
      and on DEAE-cellulose. Glycoprotein preparations from P. megasperma var. sojae
      races 1, 2, and 3 have been tested on four cultivars of soybeans. The partially
      purified glycoproteins from incompatible races of the pathogen (races that cannot
      successfully infect the plant), but not those from compatible races (races that
      can kill the plant), protect soybean seedlings from attack by compatible races.
      The seedlings are protected by introducing the glycoproteins into hypocotyl
      wounds of seedlings either 90 min prior to or at the time of inoculation of the
      wounds with mycelia of one of the pathogens. The glycoprotein preparations are
      poor nonspecific elicitors of phytoalexin accumulation; the glycoproteins have
      less than 1.0% of the elicitor activity of the glucans present in the mycelial
      walls of the pathogen.

PMID- 16592714
TI  - Role of environmental variability in the evolution of life history strategies.
AB  - We reexamine the role of environmental variability in the evolution of life
      history strategies. We show that normally distributed deviations in the quality
      of the environment should lead to normally distributed deviations in the
      logarithm of year-to-year survival probabilities, which leads to interesting
      consequences for the evolution of annual and perennial strategies and
      reproductive effort. We also examine the effects of using differing criteria to
      determine the outcome of selection. Some predictions of previous theory are
      reversed, allowing distinctions between r and K theory and a theory based on
      variability. However, these distinctions require information about both the
      environment and the selection process not required by current theory.

PMID- 16592715
TI  - Growth of complex systems can be related to the properties of their underlying
      determinants.
AB  - Growth-increase in size, number, or amount-in many cases appears to follow simple
      empirical laws. Such laws have been noted in a wide variety of fields for many
      years. Until now these laws have never been related to the underlying
      determinants of these systems. By starting with fundamental properties of the
      component mechanisms in such systems, one can derive a basic growth equation for
      which the well-known laws of growth are special cases.

PMID- 16592716
TI  - Sulfur base ligation to iron(II) and cobalt(II) porphyrins.
AB  - Equilibrium constants for the binding of sulfur bases to cobalt(II) porphyrins
      were measured in toluene solution by a spectrophotometric method. The order of
      decreasing binding strength of sulfur ligands to cobalt(II) porphyrins was found
      to be mercaptide ions >> thioethers > mercaptans. It is suggested that a similar
      stability order of these sulfur ligands should exist towards iron(II) porphyrins,
      but formation constants could be obtained only for the mercaptide ions.

PMID- 16592717
TI  - Significant structure theory applied to electrolyte solution.
AB  - The significant structure theory has been successfully applied to an aqueous NaCl
      solution. Liquid water is assumed to have a domain structure and the ions are
      hydrated by water molecules. The partition function is composed of the partition
      function for the water and that for the salt, and the excess free energy term
      from the Debye-Huckel theory is also added. The thermodynamic properties, such as
      molar volume, vapor pressure, entropy of vaporization, and heat capacity, as well
      as the dielectric constant are calculated over the whole concentration ranges and
      wide temperature ranges. The agreement between theory and experiment is
      satisfactory.

PMID- 16592718
TI  - Lower bounds for eigenvalues of self-adjoint problems.
AB  - The equation y'' + [lambda - q(x)]y = 0 on (0, infinity) or (-infinity,
      infinity), in which q(x) --> infinity as x --> infinity or x --> +/- infinity,
      has a complete set of eigenfunctions with discrete eigenvalues {lambda(n)}(n=0)
      (infinity). We derive an inequality that contains lambda(n), by using a quick and
      elementary method that does not employ a comparison theorem or assume anything
      special. Explicit lower bounds for lambda(n) can often be easily obtained, and
      three examples are given. The method also gives respectable lower bounds for
      lambda(n) in the classical Sturm-Liouville case.

PMID- 16592719
TI  - Phosphorus in Connecticut lakes predicted by land use.
AB  - The concentration of phosphorus in parts per billion (ppb) in 33 Connecticut
      lakes was predicted from information on land use and simple models for
      concentration decreases in lakes. The best predictions were obtained from
      [Formula: see text] where P is the concentration of phosphorus in ppb, Q is the
      water load on the lake in meters per year, D is the water export from the entire
      watershed in meters per year, and U, A, and W are the fractions of urban,
      agricultural, and wooded land, respectively, in the watershed. The phosphorus
      export coefficients and SEM, estimated by least squares regression, were 170 +/-
      21 mg per m(2)/yr for urban, 54 +/- 15 mg per m(2)/yr for agricultural, and 10 +/
      3 mg per m(2)/yr for wooded land. P +/- (SEM) 6.9 ppb was predicted.

PMID- 16592720
TI  - Chromophore organization in photosynthetic reaction centers: High-resolution
      magnetophotoselection.
AB  - The electron spin resonance spectrum of the triplet excited state of
      Rhodopseudomonas spheroides R-26 reaction centers has been studied after
      excitation with the polarized narrow-bandwidth output of a tunable dye laser from
      520 to 670 nm. A theory is developed relating experimental observables to the
      angles between the electronic transition dipole moment of the excited chromophore
      and the principle magnetic axis system of the triplet state of the dimeric trap.
      Data is presented which demonstrates that the treatment is correct and useful,
      and angles are obtained for the Q(x) transitions of bacteriopheophytin. High
      resolution magnetophotoselection data in the region of the bacteriochlorophyll
      Q(x) transitions can be combined with polarized photobleaching experiments to
      provide direct information on the structure of dimeric trap.

PMID- 16592721
TI  - Photoreversible absorbance changes in solutions of allophycocyanin purified from
      Fremyella diplosiphon: Temperature dependence and quantum efficiency.
AB  - Preparations of allophycocyanin isolated from the alga Fremyella diplosiphon show
      light-induced optical absorbance changes that suggest the presence of a
      photoconvertible component [Formula: see text] similar to the algal pigments
      described by J. Scheibe [(1972) Science 176, 1037-1039]. At pH < 4 the
      allophycocyanin has an absorption maximum at 620 nm. Red illumination causes a
      loss of absorbance in the red, centered at 620 nm, and subsequent green
      illumination restores the lost absorbance. We have studied this photoconversion
      at temperatures between 200 K and 307 K, analyzing the results in terms of
      photostationary states established under red (640 nm) and green (550 nm) light.
      As the temperature was lowered to 260 K, the state P(r) became progressively
      favored; the reaction P(r) --> P(g) induced by red light was attenuated but the
      reaction P(g) --> P(r) induced by green light was not. Decreasing the temperature
      from 260 K to 200 K had no further effect. Two distinct and simple models can
      account for this curious temperature dependence. By analyzing the kinetic and
      steady-state data, with reasonable estimates of the molar extinction coefficients
      of P(r) and P(g), we computed quantum efficiencies greater than 15% for the
      photoconversion at 300 K. We deduced that a conversion of "all P(r)" to "all
      P(g)" should produce a fractional absorbance change DeltaA/A at 620 nm equal to
      0.1. If the chromatic adaptation response of intact F. diplosiphon shows the
      unusual temperature dependence reported here, the system P(r) right harpoon over
      left harpoon P(g) will be implicated in mediating this response.

PMID- 16592722
TI  - Cellular localization of the insect prothoracicotropic hormone: In vitro assay of
      a single neurosecretory cell.
AB  - The distribution of prothoracicotropic hormone in the pupal brain of Manduca
      sexta has been determined by an in vitro assay for prothoracic gland activation.
      Prothoracicotropic activity was observed in both the brain and retrocerebral
      complex, but predominantly in the dorosolateral regions of the protocerebrum. Of
      the two groups of neurosecretory cells present in this area of the brain, only
      the two lateral type III neurosecretory cells exhibited significant
      prothoracicotropic hormone activity. Further analysis revealed that the
      neurohormone was localized in only one of the two type III cells, suggesting that
      a single neurosecretory cell in each hemisphere is the source of the hormone at
      the stage examined (day 0). Prothoracicotropic hormone activity was detected in
      both the corpora allata and the corpora cardiaca, but the corpora allata
      contained 2 to 9 times the activity of the corpora cardiaca, depending on
      developmental stage. The significantly higher level of activity in the corpora
      allata suggests that they may be the neurohemal organs through which the
      prothoracicotropic hormone of Manduca is released.

PMID- 16592723
TI  - Evolution of eusociality in termites.
AB  - A model is presented that demonstrates that asymmetries in relatedness such that
      individuals are more closely related to siblings than to offspring develop in
      diploid pedigrees under conditions of inbreeding. Given also certain incestuous
      conditions, the model predicts that eusocial-type helping behavior can be favored
      by natural selection. Three cases of the model are discussed along with
      implications for termite eusociality. Several aspects of termite biology,
      particularly the existence of replacement reproductives, are interpreted as
      evidence that termite eusociality may have arisen under the special conditions
      specified in the models.

PMID- 16592724
TI  - Methylation of chloroplast DNAs in the life cycle of Chlamydomonas.
AB  - Methylation patterns of Chlamydomonas chloroplast DNAs (chlDNAs) were examined in
      the vegetative, gametic, and zygotic stages of the life cycle. Restriction endo
      nuclease fragment patterns produced by EcoRI, BamHI, Hpa II, and Msp I were
      compared; the last two cleave DNA at the sequence C-C-G-G, but Hpa II is blocked
      by prior methylation of the internal cytidine whereas Msp I is not. chlDNAs from
      vegetative cells of both mating types showed no evidence of methylation at C-C-G
      G. Gametic mt+ chlDNA was heavily methylated at C-C-G-G, whereas the homologous
      chlDNA from mt- gametes showed very slight methylation at C-C-G-G. Methylation of
      additional sites in chlDNA from mt+ gametes but not from mt- gametes was shown by
      blockage of some EcoRI and BamHI sites that were cleaved in the chlDNA from
      vegetative cells. chlDNA from 6-hr zygotes was much more methylated than gametic
      mt+ DNA, as shown by its almost total resistance to cleavage by all four
      restriction enzymes. These findings support and extend previous evidence that
      chlDNA of mt+ cells is methylated during gametogenesis and that further
      methylation occurs after gametic fusion in the young zygotes.

PMID- 16592725
TI  - Genetic variability maintained in a finite population under mutation and
      autocorrelated random fluctuation of selection intensity.
AB  - By using the diffusion equation method, the level of genetic variability
      maintained under mutation pressure in a finite population is investigated,
      assuming autocorrelated random fluctuation of selection intensity. An appropriate
      mathematical model was formulated to treat the change of gene frequencies,
      incorporating mutation pressure and fluctuating selection. Extensive Monte Carlo
      simulation experiments were also performed to supplement the theoretical
      treatments. Excellent agreement between the two results suggests the validity of
      the present diffusion model for the autocorrelated selection. One of the most
      important findings from the simulation studies is that mutations and random
      sampling drift largely determine the level of genetic variability, and that the
      presence of autocorrelated selection can significantly lower genetic variability
      only when its strength, as measured by the cumulative variance of selection
      intensity, is larger than about 10(3) times the mutation rate. It is pointed out
      that the effects of both mutations and random sampling drift have to be
      incorporated in order to assess the role of various factors for the maintenance
      of genetic variability in natural populations.

PMID- 16592726
TI  - Allometric morphogenesis of complex systems: Derivation of the basic equations
      from first principles.
AB  - Allometric morphogenesis is the generation of form or pattern as a result of
      differential growth according to power-law relationships among the elements of a
      complex system. This phenomenon has been noted in a variety of fields for many
      years, in some cases for centuries, and yet it has never been related to the
      underlying determinants of the systems. By starting with fundamental properties
      of the component mechanisms in such systems, one can derive a basic growth
      equation from which the well-known law of allometric morphogenesis follows
      naturally.

PMID- 16592727
TI  - Dynamics of technological evolution: Random walk model for the research
      enterprise.
AB  - Technological evolution is a consequence of a sequence of replacements. The
      development of a new technology generally follows from model testing of the basic
      ideas on a small scale. Traditional technologies such as aerodynamics and naval
      architecture involved feasibility experiments on systems characterized by only
      one or two dimensionless constants. Technologies of the "future" such as
      magnetically confined fusion depend upon many coupled dimensionless constants.
      Research and development is modeled and analyzed in terms of random walks in
      appropriate dimensionless constant space.

PMID- 16592728
TI  - An improvement in the theory of regular solutions.
AB  - In constructing the theory of regular, nonpolar, binary solutions, the partial
      molal energy of mixing has been expressed by the square of difference between
      "solubility parameters," usually evaluated by the molal energy of vaporization
      per cubic centimeter, (DeltaE(v)/V)(1/2) = delta, at approximately 25 degrees C.
      We have found, however, that liquids whose molecules contain methyl groups do not
      conform to these parameters; to account for their solvent power for iodine
      requires parameters increased in proportion to the number of methyl groups per
      molecule. The anomaly may be attributed to the absence of outer nonbonded
      electrons able to exert London attractive force between neighboring molecules.
      Parameters derived from solubility for iodine in both methyl-containing liquids
      and fluorochemicals greatly improve the predictive power of the theory of regular
      solutions.

PMID- 16592729
TI  - Direct spectroscopic observation of singlet oxygen emission at 1268 nm excited by
      sensitizing dyes of biological interest in liquid solution.
AB  - The direct observation of dye-photosensitized 1268-nm emission of the (1)Delta(g)
      --> (3)Sigma(g) transition of molecular oxygen in liquid solution at room
      temperature is reported. Singlet oxygen was photosensitized by UV excitation of
      perfluorobenzophenone in fluorocarbon solvent, by 3,4-benzpyrene and
      hematoporphyrin in carbon tetrachloride, and by methylene blue in water. Also
      reported is the development of an extremely sensitive near-infrared
      spectrophotometer that uses a thermoelectrically cooled lead sulfide detector,
      optimized optics, and a boxcar integrator as a data processor.

PMID- 16592730
TI  - On the lowest eigenvalue of a pseudo-differential operator.
AB  - Positive lower bounds for pseudo-differential operators with nonnegative symbols
      are derived; the bounds in particular yield subelliptic estimates for operators
      arising as sums of squares of vector fields.

PMID- 16592731
TI  - Completely integrable systems and groups generated by reflections.
AB  - We introduce a class of quantum Hamiltonian systems with delta-function
      potential, related to groups generated by reflections. They generalize the system
      of equal elastic particles on the line. We show that these systems are completely
      integrable and we integrate them explicitly. Then we apply our technique to
      obtain identities for groups generated by reflections.

PMID- 16592732
TI  - Irreversible processes at nonequilibrium steady states and Lyapounov functions.
AB  - Nonequilibrium stability theory is reviewed. In answer to recent comments by Fox
      [Fox, R. F. (1979) Proc. Natl. Acad. Sci. USA 76, 2114-2117], it is pointed out
      that various choices of Lyapounov functions are possible in the nonlinear range
      of irreversible phenomena.

PMID- 16592733
TI  - Universal variational functionals of electron densities, first-order density
      matrices, and natural spin-orbitals and solution of the v-representability
      problem.
AB  - Universal variational functionals of densities, first-order density matrices, and
      natural spin-orbitals are explicitly displayed for variational calculations of
      ground states of interacting electrons in atoms, molecules, and solids. In all
      cases, the functionals search for constrained minima. In particular, following
      Percus [Formula: see text] is identified as the universal functional of Hohenberg
      and Kohn for the sum of the kinetic and electron-electron repulsion energies of
      an N-representable trial electron density rho. Q[rho] searches all antisymmetric
      wavefunctions Psi(rho) which yield the fixed. rho. Q[rho] then delivers that
      expectation value which is a minimum. Similarly, [Formula: see text] is shown to
      be the universal functional for the electron-electron repulsion energy of an N
      representable trial first-order density matrix gamma, where the actual external
      potential may be nonlocal as well as local. These universal functions do not
      require that a trial function for a variational calculation be associated with a
      ground state of some external potential. Thus, the v-representability problem,
      which is especially severe for trial first-order density matrices, has been
      solved. Universal variational functionals in Hartree-Fock and other restricted
      wavefunction theories are also presented. Finally, natural spin-orbital
      functional theory is compared with traditional orbital formulations in density
      functional theory.

PMID- 16592734
TI  - Characterization of cyanobacterial phycobilisomes in zwitterionic detergents.
AB  - Properties of cyanobacterial phycobilisomes (from Synechococcus spp. 6301 and
      6312 and Synechocystis sp. 6701) prepared in the presence of two different
      zwitterionic detergents were compared to those of phycobilisomes detached from
      membranes with the nonionic detergent Triton X-100 and then freed from Triton by
      sedimentation through high-salt sucrose density gradients. The absorption
      spectra, polypeptide composition, and ultrastructure of phycobilisomes were
      independent of the detergent used during the preparation. Phycobilisomes from
      certain cyanobacteria aggregated in the absence of detergent. Such aggregation
      was not seen in preparations containing zwitterionic detergents. Aggregation of
      phycobilisomes led to a partial quenching of their fluorescence. Electron
      microscopy showed the three types of phycobilisomes to have a hemi-disc
      appearance, although their detailed structures were quite different.

PMID- 16592735
TI  - Isolation and structure of pro-methionine-enkephalin: Potential enkephalin
      precursor from porcine hypothalamus.
AB  - A hexapeptide that we have named pro-methionine-enkephalin has been isolated from
      acid extracts of porcine hypothalami and found to have the amino acid sequence H
      Tyr-Gly-Gly-Phe-Met(O)-Arg-OH. This peptide is not a fragment of either porcine
      beta-lipotropin or beta-endorphin, which suggests that it could be a precursor of
      [Met]enkephalin in the brain by a pathway differing from the one usually
      postulated. The existence of still larger precursors of [Met]enkephalin, perhaps
      related to the recently reported alpha-neo-endorphin, is strongly implied by
      these studies. Synthetic H-Tyr-Gly-Gly-Phe-Met-Arg-OH exhibited low, but
      significant, opiate activity in vitro.

PMID- 16592736
TI  - Hormone-induced increase in levels of functional mRNA and alpha-amylase mRNA in
      barley aleurones.
AB  - Incubation of barley aleurone cells with gibberellic acid produces a progressive
      increase in the RNA content of the cells. The activity of poly(A)-containing RNA,
      measured in an in vitro wheat germ protein-synthesizing system, reaches a maximum
      approximately 12 hr after hormone addition and declines thereafter. The
      structurally intact functional mRNA content in these cells, measured as poly(A)
      RNA with 5' "caps," also shows a maximum at 12 hr and correlates with the
      translational capacity of poly(A)-RNA. Activation of mRNA by guanylylation or
      methylation after addition of gibberellic acid is ruled out. Available evidence
      indicates that gibberellic acid stimulates protein synthesis by increasing the
      synthesis of mRNA. Studies with cycloheximide suggest that the induction of
      synthesis of alpha-amylase mRNA by gibberellic acid requires protein synthesis
      after hormone addition.

PMID- 16592737
TI  - Functional reconstitution of photosynthetic reaction centers in planar lipid
      bilayers.
AB  - Planar lipid bilayers containing reaction centers from Rhodopseudomonas
      sphaeroides R-26 were formed by apposing two reaction center-lipid monolayers
      formed from a reaction center-lipid complex in hexane. Secondary donors
      (cytochrome c) and acceptors (ubiquinone-0) were added on opposite sides of the
      membrane. Upon illumination, this system generated transient and steady-state
      voltages and currents. The wavelength dependence of the photoresponse matched the
      absorption spectrum of reaction centers. A simple model based on the transfer of
      charges across the membrane that explains the salient features of the
      photoresponse is presented.

PMID- 16592738
TI  - A general ellipsoid cannot always serve as a model for the rotational diffusion
      properties of arbitrarily shaped rigid molecules.
AB  - An ellipsoidally shaped body, or more commonly, an ellipsoid of revolution, is
      generally assumed to serve as a convenient model for evaluating the rotational
      diffusion properties of macromolecules. If Perrin's equations for the rotational
      diffusion coefficients of general ellipsoids can be shown to generate all
      possible rotational diffusion coefficients, then there would exist at least one
      equivalent ellipsoidal shape for every arbitrarily shaped rigid body. We
      investigated the problem by first generating a space, r-space, representing all
      possible ellipsoidal shapes. We then generated another space, D-space,
      representing all possible combinations of rotational diffusion coefficients. We
      then mapped r-space into D-space by using Perrin's equations. Ellipsoidal shapes
      map into diffusion space in a well-defined manner. The mapping is either 1:1,
      2:1, or 3:1; several distinctly different regions of r-space map onto the same
      regions of D-space. Thus, for some combinations of rotational diffusion
      coefficients, more than one ellipsoid can be used as a model. Not all of D-space
      is covered by the mapping of r-space. Therefore, there are combinations of
      rotational diffusion coefficients that cannot be generated from ellipsoidally
      shaped bodies. Several examples of rigid body shapes with nonellipsoidal
      diffusion properties are described.

PMID- 16592739
TI  - Nonhormonal induction of H efflux from plant tissues and its correlation with
      growth.
AB  - When the esterase substrate alpha-naphthyl acetate is added to segments from
      coleoptiles of oat (Avena sativa L., var. Victory) or corn (Zea mays L., Bear
      hybrid WF 9 x 38) or to roots of lentil (Lens culinaris Med.), it is rapidly
      taken up and hydrolyzed to alpha-naphthol and acetic acid. This technique was
      used to generate intracellular acid and to study the effect of its efflux on
      growth. With corn coleoptile segments, treatment with alpha-naphthyl acetate
      induced more rapid and more prolonged growth than did exposure to external acidic
      buffers. Dose-response studies of alpha-naphthyl acetate induction of H(+)
      secretion and growth indicated the existence of a distinct threshold rate of H(+)
      efflux below which growth is not enhanced. The rate of H(+) efflux induced by
      optimal levels of auxin appears to be at or below this threshold level in corn
      coleoptile tissue. These data indicate that the relationship between external
      acidification and elongation is not a simple one and that the effectiveness of
      H(+) entering the cell wall may depend on factors not directly correlated with
      the appearance of H(+) in the external medium.

PMID- 16592740
TI  - Photosynthetic carbon reduction pathway is absent in chloroplasts of Vicia faba
      guard cells.
AB  - Four cell types from Vicia faba Linnaeus "Long Pod" leaflets were assayed for
      three enzymes unique to the photosynthetic carbon reduction pathway. The enzymes
      were ribulosebisphosphate carboxylase [3-phospho-D-glycerate carboxy-lyase
      (dimerizing), EC 4.1.1.39], phosphoribulokinase (ATP:D-ribulose-5-phosphate 1
      phosphotransferase, EC 2.7.1.19), and glyceraldehyde-phosphate dehydrogenase
      (NADP(+)) (phosphorylating) [D-glyceraldehyde-3-phosphate:NADP(+) oxidoreductase
      (phosphorylating), EC 1.2.1.13]. On a dry weight basis, these enzyme activities
      were about twice as high in palisade as in spongy parenchyma. Two of the enzymes
      were not detected in epidermal cells and the other was present in only a trace
      amount. In guard cells, these enzyme activities were absent or present at les
      than 1% of the amount in palisade cells. Immunoelectrophoresis showed that
      ribulosebisphosphate carboxylase was absent in extracts of guard cell
      protoplasts. Microscopy confirmed the abundance of typical guard cell
      chloroplasts. These results demonstrate the absence of the photosynthetic carbon
      reduction pathway in guard cell chloroplasts. This is the only chloroplast type
      known to be deficient in this pathway in plants whose primary CO(2) acceptor is
      ribulose bisphosphate. Possible reasons for the absence of this pathway in guard
      cells are discussed.

PMID- 16592741
TI  - Structure of a bacterial photosynthetic membrane.
AB  - The internal photosynthetic membranes of a photosynthetic bacterium,
      Rhodopseudomonas viridis, have been studied with a variety of electron microscope
      techniques. The membranes are composed of a sheet of apparently identical
      subunits arranged in a hexagonal fashion. The individual subunits repeat at a
      distance of 110 A. Optical transforms have been used to enhance micrographs of
      this ordered membrane, and the images synthesized in this way show details of
      each subunit. The individual subunits are asymmetric, differing slightly in
      appearance at the outer and inner surfaces of the membrane, and these surface
      patterns seem to be combined in the image of the thylakoid membrane in negative
      stain. These studies fix a maximum size for the photosynthetic unit of R. viridis
      and suggest the suitability of this membrane for further diffraction analysis.

PMID- 16592742
TI  - Kinetics of the cycloheximide-induced phase changes in the biological clock in
      Gonyaulax.
AB  - Cycloheximide, an inhibitor of protein synthesis on cytoplasmic ribosomes in
      eukaryotes, is shown to shift the phase of the circadian rhythm in stimulated
      bioluminescence in the marine dinoflagellate Gonyaulax polyedra. Kinetic analysis
      of the phase changes shows that this effect may be subdivided into two distinctly
      different and well-separated parts. The first (early) phase change occurs with 15
      min exposure to cycloheximide and is saturated at low concentrations (
      approximately 10 nM). The second (late) phase changes requires about 150 min of
      exposure to cycloheximide and is saturated at 0.36 muM cycloheximide. Twenty
      times-higher concentrations cause no further phase changes. The magnitudes of
      both early and late phase changes depend on the time of day when the cells are
      exposed to cycloheximide. Early phase changes vary from 5 hr advance at circadian
      time (CT) 20 to 1 hr delay at CT 12; late phase changes are larger, the maximal
      advance being 12 hr at CT 16 and the greatest delay, 10 hr at CT 14. It is
      proposed that the early phase changes are caused by alterations in the ion
      distribution across membranes as a consequence of the permeation of
      cycloheximide. Late phase changes may be the result of inhibition of protein
      synthesis.The phase response curve for the late phase change is identical to that
      obtained with saturating light pulses in otherwise constant darkness in
      Gonyaulax. Maximal phase changes drive the clock into the part of the circadian
      cycle between CTs 4 and 9. Perturbations in this part of the circadian cycle are
      without effect on phase. Incubation of Gonyaulax with cycloheximide for a
      critical duration at a critical time induces arhythmicity, but longer exposures
      to the inhibitor at the same time do not. This observation suggests the existence
      of a singularity in the circadian clock of Gonyaulax.

PMID- 16592743
TI  - Synthesis and processing of maize storage proteins in Xenopus laevis oocytes.
AB  - Xenopus oocytes injected with zein mRNAs efficiently synthesized maize storage
      proteins for prolonged periods. Under optimal conditions, zein was synthesized at
      3 ng/hr and represented approximately 10% of the total protein synthesized in the
      oocyte. The mRNA from the normal maize inbred line directed synthesis of all the
      major zein components; however, products of mRNA from the opaque-2 mutant did not
      contain the largest zein component. Zein proteins synthesized in the oocyte were
      2000 daltons smaller than proteins synthesized by cell-free translation of mRNAs
      in the wheat germ and reticulocyte systems. This result, which suggested that the
      oocyte processed prezein polypeptides into native zein proteins, was confirmed by
      amino-terminal sequence analysis of zein proteins from the oocytes. Cyanogen
      bromide cleavage of translation products from oocytes and the wheat germ system
      confirmed the existence of several proteins within each of the major zein
      components. However, we were unable to detect the presence of signal sequences on
      zein peptides by this technique.

PMID- 16592744
TI  - The Webster method of apportionment.
AB  - Several results concerning the problem of U.S. Congressional apportionment are
      given which, together, indicate that a method first proposed by Daniel Webster
      (also known as the "Major Fractions" method) seems fairest when judged on the
      basis of criteria suggested by common sense and precedent.

PMID- 16592745
TI  - Some recent tests of the chronometric cosmology.
AB  - Two papers comparing particular samples of galaxies and quasars with certain
      predictions of the chronometric cosmology, and reporting significant deviations,
      are shown not to be altogether correct in their theoretical procedures. It is
      shown in addition that although the data employed in these papers are in part
      privately held, published data on similar samples fit the chronometric
      predictions satisfactorily, and fail to fit nonevolutionary Friedmann models with
      conventional values for q(0). As a check on and a refinement of our statistical
      analysis, the magnitude bias was removed from several well-documented samples by
      maximum-likelihood estimation of the individual probabilities in the differential
      luminosity function, without constraint on its form. The same conclusions as
      earlier follow, both in the classic regime of bright low-redshift galaxies and
      that of quasars.

PMID- 16592746
TI  - Optical polarization and infrared spectrum of a possible protostar in a
      reflection nebula.
AB  - The star HD 200775 illuminates the reflection nebula NGC 7023. This star is one
      of a small group of Ae and Be stars associated with nebulosity and proposed by
      Herbig as candidates for newly formed stars of moderately large mass. The system
      is a part of a large dust complex more than a degree in extent. Structural
      features in the nebulosity can be traced very near to the star (several are
      seconds away) and some of these structures are highly polarized in the sense
      expected for scattered light from the central object. Although the star is
      classified as an early spectral type (B2-B8) of moderate luminosity (class IV or
      V), its energy distribution does not resemble a black body characteristic of a
      stellar photosphere. Instead, the radiated flux has the appearance of free free
      radiation (thermal bremsstrahlung) usually considered to arise in astrophysical
      situations involving optically thin plasmas of ions and free electrons. Our
      observations are consistent with the belief that HD 200775 is a protostar and
      that the surrounding material is the cocoon from which it formed. The complex
      polarized structures probably originate in material ejected by radiation pressure
      and plasma processes as the star rose in luminosity after its gravitational
      collapse.

PMID- 16592747
TI  - Significant structure theory applied to liquid He.
AB  - The large kinetic zero-point motion of (4)He molecules has been properly taken
      into account in the significant structure theory of liquids in order to describe
      the liquidity of liquid (4)He. The Debye and the Bose-Einstein partition
      functions are used for the solid-like molecules of the normal fluid component and
      for the whole gas-like molecules, respectively. The solid-like molecules of the
      superfluid component are considered as ground state molecules without having
      positional degeneracies. The Bragg-Williams approximation of an order/disorder
      phase transition has been applied to the lambda transition of liquid (4)He.
      Thermodynamic and surface properties of liquid (4)He have been calculated up to
      the critical point. The results are satisfactory when compared with the observed
      values.

PMID- 16592749
TI  - Substituent effects on the nitrogen-15 and carbon-13 shieldings of some N
      arylguanidinium chlorides.
AB  - The (13)C and (15)N chemical shifts of five N-arylguanidinium chlorides carrying
      polar substituents, ranging in character from 4-methoxy to 4-nitro groups, have
      been determined by NMR spectroscopy at the natural-abundance level of (13)C and
      (15)N in dimethyl sulfoxide solution. Comparison of the (13)C shifts of these
      salts with those of monosubstituted benzenes shows that the guanidinium group
      induces an average downfield shift of -5.8 ppm of the resonance of the aryl
      carbon to which it is attached (C1), an average upfield shift of +4.2 ppm for C2
      and C6, and a small upfield shift of +1.9 ppm for C4. The shifts of C3 and C5 are
      small and erratic relative to the corresponding carbons in monosubstituted
      benzenes. The (15)N resonances of the guanidinium nitrogens are quite sensitive
      to electric effects resulting from substitution of polar groups at C4. The (15)N
      shift of the [unk]NAr nitrogen relative to that of the salts suggests that the
      predominant tautomer for N-arylguanidines is (H(2)N)(2)C[unk]NAr. The (15)N
      shifts of the (NH(2))(2) nitrogens correlate rather well with sigma(p) (-)
      parameters, whereas the shifts of the -NHAr nitrogens seem to correlate only with
      R values derived from the sigma(p) (-) substituent constants.

PMID- 16592748
TI  - Identification of blue-green algal nitrogen fixation genes by using heterologous
      DNA hybridization probes.
AB  - In the filamentous blue-green alga Anabaena 7120, aerobic nitrogen fixation is
      linked to the differentiation of specialized cells called heterocysts. In order
      to study control of heterocyst development and nitrogen fixation in Anabaena, we
      have used cloned fragments of the Klebsiella pneumoniae nitrogen fixation (nif)
      genes as probes in DNA.DNA hybridizations with restriction endonuclease fragments
      of Anabaena DNA. Using this technique, we were able to identify and clone
      Anabaena nif genes, demonstrating the feasibility of using heterologous probes to
      identify genes for which no traditional genetic selection exists. From the
      patterns of hybridization observed, we deduced that although DNA sequence
      homology has been retained between some of the nif genes of these divergent
      organisms, the nif gene order has been rearranged.

PMID- 16592750
TI  - Photochemical dimerization of parinaric acid in lipid bilayers.
AB  - Parinaric acid (9,11,13,15-octadecatetraenoic acid), a conjugated tetraene fatty
      acid, undergoes a second-order photochemical reaction in phospholipid bilayers.
      The reaction results in the loss of the characteristic absorption of this
      chromophore and the development of new absorption demonstrating the presence of a
      triene chromophore. The progress of this reaction is easily monitored by
      measurement of the decrease in the fluorescence intensity from a uniformly
      illuminated sample. The reaction rate measured in this way is sensitive to the
      thermal phase transition of the bilayer and to the presence of cholesterol. The
      relationship of the second-order rate constant to the lipid diffusion coefficient
      is discussed. This relationship differs from that previously used for the
      analysis of similar photochemical processes.

PMID- 16592751
TI  - cis-trans photoisomerization of 1,3,5,7-octatetraene in n-hexane at 4.2 K.
AB  - Photoisomerization of the linear polyene 1,3,5,7-octatetraene has been observed
      in an n-hexane matrix maintained at the boiling point of helium. To a good
      approximation, only the trans,trans and cis,trans isomers participate in the
      photochemistry. These compounds have been unambiguously identified by comparing
      the observed high-resolution fluorescence spectra to those of chromatographically
      purified reference compounds. Although the quantum yield of this process is
      probably low, its microscopic rate seems to compete favorably with vibrational
      deactivation.

PMID- 16592752
TI  - Conductimetric determination of thermodynamic pairing constants for symmetrical
      electrolytes.
AB  - Earlier theories of electrolytic conductance are reviewed; all of these, with the
      exception of the Arrhenius-Ostwald theory, are based on physical models. Their
      theory failed to describe the conductance of strong electrolytes because it did
      not include the effects (then unsuspected) of long-range forces on mobility.
      Thermodynamic derivations are independent of model; applied to the postulated
      equilibrium A(+) + B(-) right arrow over left arrow A(+)B(-) between free ions
      and nonconducting paired ions, the thermodynamic pairing constant K(a) equals
      a(p)/(a+/-)(2), and DeltaG, the difference in free energy between paired ions
      (activity = a(p)) and free ions (activity = a(+/-)), equals (-RT ln K(a)).
      Converting to the molarity scale, K(a) = (1000 rho/M)[1 - gamma)/cy(2)(y(+/
      ))(2)]. Here rho is the density of the solvent of molecular weight M, c is
      stoichiometric concentration of electrolyte (mol/liter), gamma is the fraction of
      solute present as unpaired ions, and y(+/-) is their activity coefficient. The
      corresponding conductance function Lambda = Lambda(c;Lambda(0),R, big up tri,
      openG)involves three parameters: Lambda(0), the limiting equivalent conductance;
      R, the sum of the radii of the cospheres of the ions; and DeltaG. Conductance
      data for cesium bromide and for lithium chloride in water/dioxane mixtures and
      for the alkali halides in water are analyzed to determine these parameters.
      Correlations between the values found for R and DeltaG and properties
      characteristic of salt and solvent are then discussed.

PMID- 16592753
TI  - Electron spin resonance of O-labeled protein-peroxide radicals: Zein and edestin.
AB  - Hyperfine structure due to (17)O has been measured in irradiated zein and edestin
      after exposure to gaseous oxygen with (17)O concentrated to 24%. The observations
      prove that the free radicals produced by ionizing irradiation under vacuum at 300
      K are converted by the oxygen to protein-peroxide free radicals X-O((1))-O((2)),
      with the unpaired electron density in a pi-type orbital predominantly on the
      peroxide group. From the observed couplings, the 2p(pi) spin densities on zein
      peroxide are found to be 0.29 and 0.45 for O((1)) and O((2)), respectively; those
      on edestin-peroxide are 0.26 and 0.48 for O((1)) and O((2)), respectively.

PMID- 16592754
TI  - Supramolecular structure of stacked and unstacked regions of the photosynthetic
      membranes of Prochloron sp., a prokaryote.
AB  - Freeze-fracture replicas of the photosynthetic prokaryote Prochloron sp.,
      collected at Coconut Island, Hawaii, show that the thylakoids are differentiated
      into stacked and unstacked regions much like the thylakoids of green algae and
      higher plants. On the exoplasmic (E) fracture face, the particle density is
      greater in stacked regions ( approximately 3100 particles/mum(2)) than in
      unstacked regions ( approximately 925 particles/mum(2)). On the complementary
      protoplasmic (P) fracture face, the particle density is lower in stacked regions
      ( approximately 2265 particles/mum(2) than in unstacked regions ( approximately
      4980 particles/mum(2)). The histogram of the diameters of E face particles in
      unstacked regions shows a single broad peak centered at 80 A. In stacked regions,
      four distinct peaks, at 75, 105, 130, and 160 A, are observed. These size classes
      are virtually identical to those found on E faces of thylakoids of the green alga
      Chlamydomonas and of greening pea chloroplasts. In the latter systems, the
      different size classes of E face particles are believed to represent photosystem
      II units surrounded by variable amounts of chlorophyll a/b light-harvesting
      complex. We propose that the same interpretation applies to the thylakoids of
      Prochloron, which contain a similar chlorophyll a/b complex. Our results add to
      the evidence supporting the view of the chlorophyll a/b complex as both a light
      harvesting complex and a membrane adhesion factor. The similarity of the
      architecture of the thylakoids of Prochloron to that of green algal and plant
      chloroplasts also provides additional evidence of an evolutionary relationship
      between Prochloron and the chloroplasts of green plants.

PMID- 16592755
TI  - Auxin-induced changes in the patterns of protein synthesis in soybean hypocotyl.
AB  - The patterns of protein synthesis in elongating and mature (basal) sections of
      soybean hypocotyl were examined after incubation in a medium containing auxin
      (auxin-treated) or a medium lacking auxin (untreated). The hypocotyl sections
      (1.2 cm) were labeled with [(35)S]methionine, and polypeptide patterns were
      analyzed by one- and two-dimensional polyacrylamide gel electrophoresis. Auxin
      treatment altered the pattern of protein synthesis in both elongating and basal
      soybean hypocotyl sections. Excision of terminal segments from incubated sections
      was required to clearly observe auxin-induced changes in the synthesis of
      polypeptides. Polypeptides synthesized in terminal segments, possibly in response
      to wounding, can mask subtle changes in the spectrum of polypeptides synthesized
      in response to auxin. Cytokinin treatment caused a decrease in [(35)S]methionine
      incorporation into polypeptides and altered the pattern of protein synthesis in
      untreated and auxin-treated elongating hypocotyl sections.

PMID- 16592756
TI  - Principles of liquids working in heat engines.
AB  - The thermodynamic and thermophysical properties of liquids suggest that they
      should be powerful working fluids in heat engines. Their use requires heat
      engines based conceptually on the Stirling and Malone principles. The principles
      are explained, and then experiments on propylene are presented that demonstrate
      the principles and confirm the thermodynamic analysis.

PMID- 16592757
TI  - Nuclear and cytoplasmic genes controlling synthesis of variant mitochondrial
      polypeptides in male-sterile maize.
AB  - The polypeptides synthesized in vitro by mitochondria isolated from etiolated
      maize shoots of a number of different nuclear and cytoplasmic genotypes have been
      compared by using polyacrylamide gel electrophoresis. We have previously shown
      that mitochondria from maize plants carrying the T or C forms of cytoplasmically
      inherited male sterility (cms-T and cms-C mitochondria) can be distinguished from
      each other and from the mitochondria of normal (N) plants by the synthesis of a
      single additional or variant polypeptide species. Using lines that carry the T
      cytoplasm, and that differ principally in the presence or absence of nuclear
      "restorer" alleles that suppress the male-sterile phenotype, we find that these
      nuclear genes specifically suppress synthesis of the 13,000 M(r) variant
      polypeptide. A 21,000 M(r) polypeptide that is synthesized by N mitochondria is
      not detectable among the translation products of cms-T mitochondria from either
      restored or nonrestored lines. Results obtained with a number of lines possessing
      dominant restorer alleles from different sources indicate that it is the restorer
      gene at the Rf(1) locus that is primarily responsible for regulating synthesis of
      the 13,000 M(r) polypeptide. Mitochondria from lines with the S form of
      cytoplasmic male sterility (cms-S) were found to synthesize a group of minor
      polypeptides, ranging in molecular weight from 42,000 to 88,000, which were not
      detected in N, cms-T, or cms-C mitochondria. In the case of the S and C forms of
      male sterility no differences were found between the translation products of
      mitochondria from restored and nonrestored lines.

PMID- 16592758
TI  - Protein bodies of mung bean cotyledons as autophagic organelles.
AB  - We present evidence that protein bodies constitute the principal lytic
      compartment in storage parenchyma cells of mung bean cotyledons and propose that
      they play a role in cellular autophagy. We developed a method to isolate protein
      bodies by incubating tissue slices with cell wall-degrading enzymes and
      fractionating the cellular organelles on a Ficoll gradient. About 75-80% of the
      protein bodies present in the protoplasts were recovered intact in a band at the
      5/25% Ficoll interface. This band contained a similar proportion of the cellular
      alpha-mannosidase, N-acetyl-beta-glucosaminidase, ribonuclease, acid phosphatase,
      phosphodiesterase, and phospholipase D. beta-Amylase was present in the cells but
      not in the protein bodies. Ultrastructural observations showed that on the 3rd
      day of seedling growth protein bodies contain small vesicles (0.3-1.0 mum) with a
      cytoplasmic content (ribosomes, membrane vesicles, mitochondria). Later in
      seedling growth these vesicles appeared empty. We believe that these are
      autophagic vesicles resulting from invaginations of the protein body membrane and
      that their cytoplasmic contents are digested by the acid hydrolases present in
      the protein bodies.

PMID- 16592759
TI  - Do energetic heavy nuclei penetrate deeply into Earth's atmosphere?
AB  - We calculate the expected fluxes of cosmic ray nuclei with charge 5 </= Z </= 28
      at various depths in the earth's atmosphere, taking into account the initial
      charge distribution, ionization loss, and various modes of fragmentation. The
      flux of surviving heavy nuclei is too low by a factor approximately 10(-10) to
      account for the ultra-high-energy Centauro events. We describe an experiment to
      search for highly ionizing particles that may or may not be nuclei.

PMID- 16592760
TI  - Relation between the local field at large distances from a charge or dipole and
      the dielectric constant.
AB  - The local field at large distances from a charged or dipolar impurity in a
      nonpolar polarizable fluid is related to the dielectric constant of the medium.
      The predicted local field agrees accurately with molecular dynamics results. In
      contrast, the usual continuum theory prediction is only accurate to first order
      in the polarizability and leads to serious error for realistic values of the
      polarizability. At smaller distances these relations cannot be used to define a
      physically reasonable local dielectric constant and consequently the local field
      is more satisfactorily described in terms of a screening function.

PMID- 16592761
TI  - "Sexual" behavior in parthenogenetic lizards (Cnemidophorus).
AB  - All-female, parthenogenetic species afford a unique test of hypotheses regarding
      the nature and evolution of sexuality. Basic data on the behavior of parthenogens
      are lacking, however. We have discovered, from observations of captive
      Cnemidophorus uniparens, C. velox, and C. tesselatus, behavior patterns
      remarkably similar to the courtship and copulatory behavior of closely related
      sexual species. Briefly, in separately housed pairs, one lizard was repeatedly
      seen to mount and ride its cagemate and appose the cloacal regions. Dissection or
      palpation revealed that, in each instance, the courted animal was reproductively
      active, having ovaries containing large, preovulatory follicles, while the
      courting animal was either reproductively inactive or postovulatory, having
      ovaries containing only small, undeveloped follicles. These observations are
      significant for the questions they raise. For example, is this behavior a
      nonfunctional vestige of the species' ancestry, or is this behavior necessary for
      successful reproduction in the species (e.g., by priming reproductive
      neuroendocrine mechanisms as has been demonstrated in sexual species)?

PMID- 16592762
TI  - Triplet phase invariants: Formula for acentric case from fourth-order
      determinantal joint probability distributions.
AB  - A conditional probability distribution for triplet invariants is derived for
      noncentrosymmetric crystals from fourth-order determinantal joint probability
      distributions. The formula makes use of the entire data set in the computations
      for each invariant. Test calculations indicate that the formula can be used to
      help select invariants whose values are distributed close to zero and also to
      evaluate special invariants associated with seminvariant phases.

PMID- 16592763
TI  - An optimal multiple decision rule for signs of parameters.
AB  - The problem of simultaneously deciding the signs of p parameters based on
      normally distributed estimators is considered. A decision that a parameter is too
      close to zero to decide its sign is allowed in order that the probability of at
      least one incorrect decision can be kept less than a preassigned value. Concepts
      of upper-convexity and local optimality are defined, and for p = 2 or 3 the
      locally optimal rules in the class of upper-convex rules are found. Critical
      values and operating characteristics are given for the locally optimal rule and
      some other plausible rules when p = 2.

PMID- 16592764
TI  - Average time until fixation of a mutant allele in a finite population under
      continued mutation pressure: Studies by analytical, numerical, and pseudo
      sampling methods.
AB  - We consider a single locus, and denote by A the wild-type allele and by A' the
      mutant allele that is produced irreversibly in each generation from A at the rate
      v. Let 1 + s, 1 + h, and 1 be, respectively, the relative fitnesses of mutant
      homozygote A'A', mutant heterozygote A'A, and wild-type homozygote AA. Then, it
      is shown, on the basis of the diffusion equation method, that the average time
      until fixation of the mutant allele (A') in a randomly mating population of
      effective size N(e), given that the initial frequency is p, is [Formula: see
      text] in which B(x) = (S/2)x(2) + Hx(1 - x), S = 4N(e)s, H = 4N(e)h, and V =
      4N(e)v. Of particular interest are the cases in which the mutant allele is
      deleterious (s = -s', s' > 0). Three cases are considered; the mutant is: (i)
      completely dominant s = h = -s', (ii) completely recessive s = -s', h = 0, and
      (iii) semidominant s = -s', h = -s'/2, in which s' is the selection coefficient
      against the mutant homozygote. It is shown that the average time until fixation
      is shorter when the deleterious mutant allele is dominant than when it is
      recessive if 4N(e)v is larger than 1. On the other hand, the situation is
      reversed if 4N(e)v is smaller than 1. It is also shown that for a mutant allele
      for which N(e)s' > 10, it takes such a long time until fixation that we can
      practically ignore the occurrence of random fixation of a deleterious allele
      under continued mutation pressure. To supplement the analytical treatment,
      extensive simulation experiments were performed by using a device called the
      pseudo-sampling variable, which can enormously accelerate the process of
      simulation by a computer. This method simulates the diffusion process itself
      rather than the binominal sampling process (in population genetics the diffusion
      model is usually regarded as an approximation of the discrete binomial sampling
      process).

PMID- 16592765
TI  - Selection limits and strategies.
AB  - Strategies are analyzed for maximizing the ultimate limit to truncation selection
      for a quantitative trait in finite populations. By using a formulation of Kimura
      and Crow [Kimura, M. & Crow, J. F. (1978) Proc. Natl. Acad. Sci. USA 75, 6168
      6171], it is shown that the limit is maximized by truncating at the mode with the
      highest ordinate of the phenotypic distribution. This implies 50% selection for
      the normal or any unimodal symmetric distribution and, for skewed distributions,
      selection of more than one-half if desired phenotypes are in the long tail of the
      distribution, less than one-half if in the short tail. For dioecious populations,
      the optimal procedure requires, in addition, equal numbers recorded and selected
      of each sex. For monoecious populations the limit can be improved by using the
      best individuals mated to the next-best individuals. Limitations of the results
      are discussed.

PMID- 16592766
TI  - Relationships between cytokinin production, presence of plasmids, and fasciation
      caused by strains of Corynebacterium fascians.
AB  - Cytokinin activity in the culture medium of four pathogenic strains of
      Corynebacterium fascians varied from 168 to 0.4 mug of kinetin (6
      furfurylaminopurine) equivalents per liter, as compared to 0.2 in an avirulent
      control. N(6)-Isopentenyladenine was the predominant cytokinin in the medium of
      all five strains, and its increased production was correlated with the degree of
      pathogenicity; however, the virulent strains also produced 8-13 times more cis
      zeatin [6-(4-hydroxy-3-methyl-cis-2-butenylamino)purine] than the avirulent
      strain. The three most virulent strains (with the higher cytokinin contents in
      the medium) contained a large (M(r) approximately 10(8)) plasmid. The barely
      virulent strain contained a smaller plasmid. No plasmid was detected in the
      avirulent control. The total cytokinin content (mole%) and biological activity
      (mug of kinetin equivalent per mg of tRNA) in tRNA were about the same in all
      three virulent strains and in the avirulent control. Five cytokinins were
      isolated from each strain. Four were rigorously characterized as 6-(4-hydroxy-3
      methyl-cis-2-butenylamino)-9-beta-D-ribofuranosylpurin e, 6-(3-methyl-2
      butenylamino)-9-beta-D-ribofuranosylpurine, and their 2-methylthio derivatives.
      The fifth cytokinin was tentatively identified as 6-(4-hydroxy-3-methyl-trans-2
      butenylamino)-9-beta-D-ribofuranosylpur ine. Ribosyl-cis-zeatin was 3-fold higher
      and N(6)-isopentenyladenosine was correspondingly lower in the plasmid-containing
      strains than in the plasmidless control. Because the entire syndrome of
      fasciation caused by infection can be induced with synthetic cytokinins, the
      disease would appear to be caused by plasmid-induced high rates of cytokinin
      production by the bacteria.

PMID- 16592767
TI  - Self-fertilization and monogenic strains in natural populations of terrestrial
      slugs.
AB  - Electrophoretic studies of genetic variation in 14 species of terrestrial slugs
      of the families Arionidae, Philomycidae, and Limacidae in the eastern United
      States indicate that self-fertilization, either facultative or obligatory, is the
      normal breeding system in six of the species. Three of these six species are
      single monogenic strains; one consists of three monogenic strains; one includes a
      highly heterozygous form and two monogenic strains; and one has a moderate amount
      of polymorphism but little heterozygosity and strong linkage disequilibrium.
      Eight species are outcrossers, being highly polymorphic and panmictic within
      local populations. Niche breadth, assessed in terms of extent of geographic
      distribution and variety of habitats occupied and measured on an experimental
      plot of woodland, is greater in some monogenic strains than in highly
      heterozygous, outcrossing species. Colonizing success apparently is independent
      of the amount of genetic variation carried by a species.

PMID- 16592768
TI  - L-Glutamic acid as a mediator of sexual morphogenesis in Volvox capensis.
AB  - In Volvox capensis the development of sexual individuals is in response to low
      concentrations (68 nM) of L-glutamic acid rather than to such species-specific
      glycoproteins as have been isolated in Volvox carteri or are believed to exist in
      a number of other species. V. capensis grows equally as well in light and in
      darkness in a medium supplemented with sodium acetate; however, L-glutamic acid
      is active as an inducer of the sexual form only in populations grown in the
      light. The site of action of L-glutamic acid and its biochemical role in the
      sexual response are unknown. Attempts to induce the sexual response by using the
      other L-amino acids, various analogs of glutamic acid, compounds of similar
      structure (e.g., gamma-aminobutyric acid), and intermediates of biochemical
      pathways known to involve L-glutamic acid (e.g., alpha-ketoglutarate or
      pyroglutamic acid) have been unsuccessful. L-Glutamic acid is produced by V.
      capensis as a natural product of the digestion of the glycoproteinaceous parental
      matrix at the time young spheroids escape. As a population increases, so does the
      level of L-glutamic acid produced at each succeeding generation until the
      threshold of sensitivity is reached and the induction of sexual forms is
      effected. This serves as a mechanism for ensuring the production of sexual
      spheroids and their zygotes, the only phase in the life cycle resistant to
      drying. Thus, Volvox is especially adapted to an existence in ephemeral pools of
      water resulting from seasonal rains.

PMID- 16592769
TI  - Quantitative genetic variation of enzyme activities in natural populations of
      Drosophila melanogaster.
AB  - The genetic component of variation of enzyme activity in natural populations of
      Drosophila melanogaster was investigated by using two sets of chromosome
      substitution lines. The constitution of a line of each type is: i(1)/i(1);+(2)/
      +(2);i(3)/i(3) and i(1)/i(1);i(2)/ i(2);+(3)/+(3), where i refers to a chromosome
      from a highly inbred line and + refers to a chromosome from a natural population.
      The + but not the i chromosomes vary within a set of lines. By use of a
      randomized block design to test and estimate components of variance, 50 of the
      second- and 50 of the third- chromosome substitution lines have been screened for
      variation in the activity levels of seven enzymes. Six of the seven enzymes show
      a significant genetic component in at least one set of lines, and five of the
      seven enzymes show activity variations attributable to factors that are not
      linked to the structural gene. These unlinked activity modifiers identify
      possible regulatory elements. Analyses of covariance show that most of the
      genetic variation of enzyme activities cannot be accounted for by genetic
      variation of live weight or protein content. These results and the lack of strong
      correlations between the genetic effects on the activities of different enzymes
      indicate that the effects are mainly specific for individual enzymes.

PMID- 16592770
TI  - Enzyme null alleles in natural populations of Drosophila melanogaster:
      Frequencies in a North Carolina population.
AB  - A Raleigh, NC, population of Drosophila melanogaster was sampled for the presence
      of enzyme null alleles at 25 loci. No nulls were found at any of five X-linked
      loci. Nulls were recovered at 13 of 20 autosomal loci; the weighted mean
      frequency for all 20 autosomal loci was estimated to be 0.0025. A consideration
      of the effects of these null alleles on viability strongly suggests that,
      although they may contribute to so-called polygenic variation, they are not
      representative of the entire genome.

PMID- 16592771
TI  - Conserved densities.
AB  - Conserved densities for Hamiltonian systems are shown to satisfy simple linear
      equations. These are essentially the original equations linearized around a
      particular solution. A number of examples are displayed, which pertain to many
      systems of physical interest.

PMID- 16592772
TI  - Properties of some three-state, steady-state Ising systems, according to the
      Bragg-Williams approximation.
AB  - We consider the steady-state properties of a lattice of three-state, cycling
      enzyme molecules, with nearest-neighbor interactions treated by the Bragg
      Williams (mean field) approximation. Only a few particular cases are examined,
      but these illustrate the rich phase-transition possibilities of this class of
      systems. "Bifurcation" cases were treated in a previous paper; the present
      examples are of the nonbifurcation type. However, a few new theoretical
      properties of bifurcation cases are included.

PMID- 16592773
TI  - Hydroboration kinetics: Unusual kinetics for the reaction of 9
      borabicyclo[3.3.1]nonane with representative alkenes.
AB  - The kinetics of hydroboration of alkenes with 9-borabicyclo[3.3.1]nonane dimer,
      (9-BBN)(2), exhibit interesting characteristics. With more reactive alkenes, such
      as 1-hexene, 2-methyl-1-pentene, 3,3-dimethyl-1-butene, and cyclopentene, the
      reaction exhibits first-order kinetics, first order in (9-BBN)(2) and zero order
      in alkene. On the other hand, with less reactive alkenes, such as cyclohexene, 1
      methylcyclohexene, and 2,3-dimethyl-2-butene, the reaction exhibits three-halves
      order kinetics, first order in alkene and one-half order in (9-BBN)(2). These
      kinetics can be accounted for in terms of the following mechanism:(9-BBN)(2)
      right arrow over left arrow 2 9-BBN9-BBN + alkene --> B-alkyl-9-BBNIn the case of
      the more reactive alkenes, the rate-determining step is the dissociation of the
      dimer. With less reactive alkenes, the reaction of the alkene with the monomer
      becomes the rate-determining step. For certain alkenes, such as 2-methyl-2-butene
      and cis-3-hexene, neither of the two steps is a decisive rate-determining step.
      Therefore, the reaction exhibits kinetic behavior between that of first- and
      three-halves-order kinetics.

PMID- 16592774
TI  - Comparison of rotational barriers of related diphenylmethyl anions and cations
      studied by C NMR spectroscopy: Mechanistic and structural considerations.
AB  - The rotational barriers of diphenylmethyl anions and cations were measured
      through their temperature-dependent (13)C NMR spectra. The ground state
      structures were found to possess a symmetrical propeller nature. The mechanism
      for phenyl rotation involves a nonsynchronous process, in which in the transition
      state one ring is coplanar with, and the other is perpendicular to, the plane
      formed by the central carbon and its bonds. The barriers of rotation in the
      carbanions vary with the strength of chelation of the potassium gegenion, whereas
      the (13)C NMR shifts remain unaffected. Changing substituents in the para
      position of the aromatic rings allowed both the elucidation of structure and
      mechanism and the observation of effects of changes in electron distribution on
      the height of the barrier and the (13)C NMR shifts.

PMID- 16592775
TI  - Anticholinergic substances: A single consistent conformation.
AB  - An interactive computer-graphics analysis of 24 antagonists of acetylcholine at
      peripheral autonomic post-ganglionic (muscarinic) nervous junctions and at
      similar junctions in the central nervous system, the crystal structures of which
      are known, has led to the determination of a single, consistent, energetically
      favorable conformation for all 24 substances, although their observed crystal
      structure conformations vary widely. The absolute configuration and the single,
      consistent (ideal) conformation of the chemical groups required for maximum
      anticholinergic activity are described quantitatively.

PMID- 16592776
TI  - Strongly nonlinear parabolic variational inequalities.
AB  - An existence and uniqueness result is established for a general class of
      variational inequalities for parabolic partial differential equations of the form
      partial differentialu/ partial differentialt + A(u) + g(u) = f with g
      nondecreasing but satisfying no growth condition. The proof is based upon a type
      of compactness result for solutions of variational inequalities that should find
      a variety of other applications.

PMID- 16592777
TI  - Nonlinear wave equations and constrained harmonic motion.
AB  - The study of the Korteweg-deVries, nonlinear Schrodinger, Sine-Gordon, and Toda
      lattice equations is simply the study of constrained oscillators. This is likely
      to be true for any nonlinear wave equation associated with a second-order linear
      problem.

PMID- 16592778
TI  - Geometrical gauge theory of ghost and Goldstone fields and of ghost symmetries.
AB  - We provide a geometrical identification of the ghost fields, essential to the
      renormalization procedure in the non-Abelian (Yang-Mills) case. These are some of
      the local components of a connection on a principal bundle. They multiply the
      differentials of coordinates spanning directions orthogonal to those of a given
      section, whereas the Yang-Mills potential multiplies the coordinates in the
      section itself. In the case of a supergroup, the ghosts become commutative for
      the odd directions, and represent Nambu-Goldstone fields. We apply the results to
      chiral "flavor" SU(3)(L) x SU(3)(R) and to SU(2/1). The latter reproduces a
      highly constrained Weinberg-Salam model.

PMID- 16592779
TI  - Preferential transcription of cloned maize chloroplast DNA sequences by maize
      chloroplast RNA polymerase.
AB  - Zea mays chloroplast DNA-dependent RNA polymerase in vitro preferentially
      transcribes maize chloroplast DNA sequences incorporated in cloned chimeric
      bacterial plasmids. Preferential transcription is dependent on the presence of a
      27.5-kilodalton polypeptide, the S factor, which has been purified from maize
      chloroplasts, and also on the template's being in the supercoiled form.

PMID- 16592780
TI  - Purification of a manganese-containing protein involved in photosynthetic oxygen
      evolution and its use in reconstituting an active membrane.
AB  - Extraction of thylakoid membranes with cholate in the presence of ammonium
      sulfate inactivated oxygen evolution and liberated a managanese-containing
      protein. This protein could be combined with preformed liposomes containing the
      depleted thylakoid membranes to restore 85% of the original oxygen-evolution
      activity. The protein did not affect the primary photochemical events of
      photosystem I or photosystem II, and it was required only for electron transport
      in which water was the electron donor. The protein has been purified to
      homogeneity and has an apparent molecular weight of 65,000 (polyacrylamide gel
      electrophoresis in the presence of sodium dodecyl sulfate). Atomic absorption
      revealed two atoms of manganese bound to each 65,000-dalton protein molecule.
      Treatment with alkaline Tris removed the bound manganese and rendered the protein
      incapable of restoring oxygen evolution; however, Tris treatment of the depleted
      membranes before reconstitution had no effect. Thus, this manganese protein is
      probably the site of Tris action in isolated chloroplasts and is at least part of
      the water-oxidation enzyme system.

PMID- 16592781
TI  - International Ultraviolet Explorer satellite observations of seven high
      excitation planetary nebulae.
AB  - Observations of seven high-excitation planetary nebulae secured with the
      International Ultraviolet Explorer (IUE) satellite were combined with extensive
      ground-based data to obtain electron densities, gas kinetic temperatures, and
      ionic concentrations. We then employed a network of theoretical model nebulae to
      estimate the factors by which observed ionic concentrations must be multiplied to
      obtain elemental abundances. Comparison with a large sample of nebulae for which
      extensive ground-based observations have been obtained shows nitrogen to be
      markedly enhanced in some of these objects. Possibly most, if not all, high
      excitation nebulae evolve from stars that have higher masses than progenitors of
      nebulae of low-to-moderate excitation.

PMID- 16592782
TI  - Mechanisms of triboluminescence.
AB  - The purpose of this paper has been to develop the theoretical treatment of the
      triboexcitation mechanisms due to the electric field effect and the pressure
      effect and to show how to analyze the triboluminescent spectra to determine the
      external factors that affect or induce the triboluminescence.

PMID- 16592783
TI  - Index theory for the boundaries of complex analytic varieties.
AB  - A result of boundary p-index is presented for a vector bundle on a complex
      analytic variety with boundary. A characterization of which odd-dimensional, real
      submanifolds of [unk](N) are boundaries of complex subvarieties (respectively
      submanifolds) in [unk](N) is given.

PMID- 16592784
TI  - Generic Galois extensions.
AB  - We define the notion of a generic Galois extension with group G over a field F.
      Let R be a communtative ring of the form F[x(1),..., x(n)](1/s) and let S be a
      Galois extension of R with group G. Then S/R is generic for G over F if the
      following holds. Assume K/L is a Galois extension of fields with group G and such
      that L superset, dbl equals F. Then there is an F algebra map f:R --> L such that
      K congruent with S [unk](R)L. We construct generic Galois extensions for certain
      G and F. We show such extensions are related to Noether's problem and the
      Grunwald-Wang theorem. One consequence is a simple proof of known counter
      examples to Noether's problem. On the other hand, we have an elementary proof of
      a chunk of the Grunwald-Wang theorem, and in a more general context. In fact, we
      have a Grunwald-Wang-type theorem whenever there is a generic extension for a
      group G over a field F.

PMID- 16592785
TI  - X-ray scattering by cybotactic nematic mesophases.
AB  - A structural model is proposed to account fully for observed x-ray scattering by
      certain nematic mesophases above their transition to smectic-C phases. In an
      external magnetic field, the constituent molecules tend to align into nearly
      periodic parallel chains that give rise to disc-like intensity distributions
      along the meridian in reciprocal space. Close to the transition temperature, the
      chains aggregate into parallel sheets which cause a ring-shaped intensity rise in
      these dises. The planar array in the cybotactic nematic bears a close similarity
      to that in cholesteric mesophases.

PMID- 16592786
TI  - Biosynthesis and assembly of the proton-translocating adenosine triphosphatase
      complex from chloroplasts.
AB  - The H(+)-translocating ATPase complex of chloroplasts consists of at least eight
      nonidentical subunits. Five of these (alpha, beta, gamma, delta, and epsilon
      subunits) collectively constitute the globular extramembranous CF(1) portion of
      the complex. The remaining three subunits (I-III) represent the membrane-embedded
      portion. Biosynthesis and assembly of these subunits were studied by pulse
      labeling isolated spinach chloroplasts in the presence of cycloheximide or
      chloramphenicol and by translating total leaf RNA in a rabbit reticulocyte
      system. The labeled products were analyzed by immunoprecipitation with subunit
      specific antisera or by isolating the entire H(+)-translocating ATPase complex in
      a nearly pure state. We found that chloroplasts synthesize the alpha, beta,
      gamma, and epsilon subunits of CF(1), the membrane-embedded subunit I, and
      probably also the membrane-embedded subunit III. The delta subunit (and probably
      also subunit II) are imported from the cytoplasm via larger precursor forms.
      After isolated chloroplasts are labeled in the presence of cycloheximide, the
      chloroplast-made H(+)-ATPase subunits are assembled into a complex that is
      indistinguishable from the authentic H(+)-ATPase complex. This assembly indicates
      that isolated chloroplasts contain excess pools of the cytoplasmically made
      subunits.

PMID- 16592787
TI  - Crossreactivity between the light-emitting systems of distantly related
      organisms: Novel type of light-emitting compound.
AB  - Dinoflagellate luciferin has been found to crossreact and emit light with
      euphausid photoprotein; and euphausid fluorescent substance gives luminescence
      with dinoflagellate luciferase. Luciferin and the fluorescent substance, both
      highly unstable and fluorescent compounds, are biochemically similar but not
      identical. Preliminary spectral and chemical data suggest that both compounds
      contain an open-chain polypyrrole structure, novel among compounds so far known
      to be involved in light emission in any biological system. The dinoflagellates
      and euphausids are phylogenetically distant; the possibility that the latter
      obtain the molecule nutritionally from the former is suggested.

PMID- 16592788
TI  - Population oscillations and energy reserves in planktonic cladocera and their
      consequences to competition.
AB  - Time lags in an individual's response to decreased food densities are responsible
      for oscillations in laboratory populations of Daphnia galeata mendotae. Visible
      energy reserves of triacylglycerols accumulate in the body of animals at low
      population densities when food is abundant and are later metabolized at high
      population densities when food is scarce to temporarily sustain activity and
      reproduction. After these energy reserves are metabolized many individuals,
      primarily juveniles, starve and die. The length of the time lags is a function of
      the amount of energy reserve accumulated in the individual. Because this
      sustained activity and reproduction further decreases food concentrations to very
      low levels, individuals of a second smaller-body-sized species, Bosmina
      longirostris, that do not have sufficient energy reserves quickly starve and die.
      Thus the accumulation of energy reserves in individuals underlies the time lags
      important in causing population oscillations and has consequences to
      interspecific competition.

PMID- 16592789
TI  - Guided solitary waves.
AB  - Transversely periodic solitary-wave solutions of the Boussinesq equations (which
      govern wave propagation in a weakly dispersive, weakly nonlinear physical system)
      are determined. The solutions for negative dispersion (e.g., gravity waves) are
      singular and therefore physically unacceptable. The solutions for positive
      dispersion (e.g., capillary waves or magnetosonic waves in a plasma) are
      physically acceptable except in a limited parametric interval, in which they are
      complex. The two end points of this interval are associated with (two different)
      resonant interactions among three basic solitary waves, two of which are two
      dimensional complex conjugates and the third of which is one-dimensional and
      real.

PMID- 16592790
TI  - Electron density functions for simple molecules.
AB  - Trial electron density functions have some conceptual and computational
      advantages over wave functions. The properties of some simple density functions
      for H(+) (2) and H(2) are examined. It appears that for a diatomic molecule a
      good density function would be given by rho = N(A(2) + B(2)), in which A and B
      are short sums of s, p, d, etc. orbitals centered on each nucleus. Some examples
      are also given for electron densities that are appropriate for excited states.

PMID- 16592791
TI  - Elementary transition state theory of the Soret and Dufour effects.
AB  - The elementary transition state approach has been used to obtain a simple model
      theory for the Soret effect (thermal diffusion) and the Dufour effect. The flow
      of heat in the Dufour effect is identified as the transport of the enthalpy
      change of activation as molecules diffuse. The theory as now formulated applies
      only to thermodynamically ideal mixtures of substances with molecules of nearly
      equal size. The results of the theory conform to the Onsager reciprocal
      relationship. When the results were fit to data on thermal diffusion for two
      liquid systems, a close fit was obtained and yielded reasonable values of between
      2 and 3 kcal mol(-1) for enthalpy changes of activation and differences between
      the entropy changes of activation for the two components of between 0 and 1 cal
      K(-1) mol(-1).

PMID- 16592792
TI  - Benzocyclobutene-o-xylylene valence tautomerization: Oxygen and sulfur analogs.
AB  - Gas phase pyrolysis of o-hydroxybenzyl alcohol at 750 degrees C gave o
      quinonemethide, which, on isolation, formed a mixture of the corresponding dimer
      and trimer. However, pyrolysis of o-hydroxy-[1-(4-pentenyl)]benzyl alcohol
      permitted intramolecular trapping of the intermediate o-quinonemethide, giving
      3,4-trimethylene-3,4-dihydrobenzochroman. In contrast, gas phase pyrolysis of o
      mercaptobenzyl alcohol readily gave benzo[b]thiete in good yield. The pyrolysis
      makes this interesting highly strained molecule readily available for study and
      synthetic application. Preliminary results showed that benzo[b]thiete readily
      undergoes thermal dimerization, ring-opening reactions with nucleophiles, and a
      variety of Diels-Alder reactions.

PMID- 16592793
TI  - Analytical approximation to the accessible surface area of proteins.
AB  - We propose an analytical substitute to the geometrical construction that is
      commonly used in calculating the protein surface area that is accessible to the
      solvent. A statistical approach leads to an expression of accessible surface
      areas as a function of distances between pairs of atoms or of residues in the
      protein structure, assuming only that these atoms or residues are randomly
      distributed in space but not penetrating each other. This function gives good
      estimates of the accessible surface area and of the area buried in subunit
      contacts for a number of proteins. Its evaluation is very fast, and the function
      can be differentiated, which opens the way to new applications of accessibility
      measurements in the study of proteins. As an example, we show that the presence
      of domains is easily detected by an automatic procedure based on surface areas
      only.

PMID- 16592794
TI  - Structure-sensitive resonance Raman bands of capped tetraphenylporphyrinatoiron
      complexes.
AB  - Resonance Raman spectra have been determined for the capped
      tetraphenylporphyrinatoiron complexes and their base adducts. The five-coordinate
      mono-base complexes of these porphyrin complexes display Raman spectra that are
      nearly identical to those previously determined for five-coordinate iron(II)
      tetraphenylporphyrin complexes in the marker regions around 1540, 1345, and 370
      cm(-1). A similar correspondence is found between Raman bands of iron(II)
      complexes of the capped complexes and those of tetraphenylporphyrin. By contrast,
      the unusual pseudo-six-coordinate iron(II) complexes more closely resemble high
      spin five-coordinate systems in the 1540 and 1345 cm(-1) regions, but in the 380
      cm(-1) region the resemblance is closer to the low-spin six-coordinate
      tetraphenylporphyrin complexes. These results provide spectroscopic confirmation
      for the unique nature of these pseudo-six-coordinate complexes.

PMID- 16592796
TI  - Geometrical model for the energy of semicoherent interphase interfaces.
AB  - The basis for the considerations given in this paper is the O-lattice description
      of crystalline interfaces of Bollmann. In the development of his approach
      presented here, all possible interfacial planes between two crystal phases having
      a defined orientation relationship are considered. The energies of these
      interfaces are then computed in terms of the energies of the primary intrinsic
      dislocations. A number of modeling interactions are incorporated into this
      approach, and a better agreement with experimental data is thus obtained.

PMID- 16592795
TI  - Self-assembled chlorophyll a systems as studied by californium-252 plasma
      desorption mass spectroscopy.
AB  - Self-assembled chlorophyll a and pheophytin a systems in thin solid films have
      been studied by (252)Cf plasma desorption mass spectrometry (PDMS). The (252)Cf
      PDMS spectra of these films show monomer cation and anion molecular ions, ions of
      molecular aggregates, and positive and negative ion fragmentation patterns
      arising from the loss of various aliphatic side chains from the chlorin ring.
      Chlorophyll a films cast from dry carbon tetrachloride solution, in which
      chlorophyll a is known to occur as the dimer, produced an abundant dimer ion. The
      highest degree of chlorophyll a self-assembly was observed in chlorophyll a films
      cast from n-octane solutions. Oligomer ions extending upwards in size to the
      heptamer were detected in this system.

PMID- 16592797
TI  - Bathymetry and temperature of some glacial lakes in Wyoming.
AB  - On the west flank of the Wind River Mountains, Wyoming, are several large lakes
      occupying glacially scoured depressions dammed by terminal moraines. Fremont,
      Willow, and New Fork Lakes, having maximal depths of 185, 85, and 62 m,
      respectively, are not only deep, but in 1970-1978 they had no measurable
      coliform. They have exceptionally low values of total dissolved solids; Fremont
      Lake has only 12.8 mg/liter, probably the second most dilute large lake in
      coterminus United States. Summer mixing is restricted to the uppermost 10 m,
      below which the lakes are essentially isothermal at the maximum density
      temperature, about 3.9 degrees C.

PMID- 16592798
TI  - Nonexistence of global solutions of squareu = F(u) and of squarev = F'(v)v in
      three space dimensions.
AB  - The symbol square denotes the operator partial differential(2)/ partial
      differential(2) - Delta in three space dimensions, and F denotes a function with
      F(0) = F'(0) = 0, inf F'' > 0. It is shown that u(x,t) identical with 0, if
      squareu = F(u(tt)) for xin R(3), t >/= 0, provided u,u(t),u(tt) for t = 0 have
      compact support. Similarly v(x,t) identical with 0 if squarev = F'(v(t))v(tt) for
      x in R(3), t >/=0, provided v,v(t) for t = 0 have compact support and satisfy
      integral[v(t) - F(v(t))]dx >/= 0. This shows that the global existence theorem
      proved by S. L. Klainerman [(1980) Commun. Pure Appl. Math. 33, in press] in more
      than five space dimensions is not valid for three dimensions. The theorems also
      imply instability at rest of certain hyperelastic materials.

PMID- 16592799
TI  - Mode of inhibition of electron transport by orthophenanthroline in chromatophores
      and reaction centers of Rhodopseudomonas sphaeroides.
AB  - In Rhodopseudomonas sphaeroides, light causes the transfer of electrons from
      bacteriochlorophyll to ubiquinone in the photochemical reaction centers.
      Electrons from this "primary" ubiquinone move on to a secondary ubiquinone. We
      have studied the manner in which o-phenanthroline inhibits the transfer of
      electrons from primary to secondary ubiquinone in chromatophores
      (intracytoplasmic membrane fragments) and isolated reaction centers of Rp.
      sphaeroides. The formation of anionic semiquinones, both primary and secondary,
      is signaled by an absorption band at 450 nm and by band shifts of
      bacteriopheophytin and bacteriochlorophyll in the near infrared. The pattern of
      band shifts is different for primary and secondary semiquinone, allowing us to
      distinguish which quinone has become semireduced. This point was established for
      isolated reaction centers [Vermeglio, A. & Clayton, R. K. (1977) Biochim.
      Biophys. Acta 461, 159-165] and is confirmed here for chromatophores. By adding o
      phenanthroline at various times during a sequence of actinic light flashes and
      monitoring the resulting optical absorbance changes, we have found that o
      phenanthroline inhibits electron transfer from primary semiquinone to secondary
      quinone if the latter is in its oxidized form, but not if the latter is
      semireduced. Our findings can explain the decay kinetics of delayed fluorescence
      from bacteriochlorophyll in Rp. sphaeroides as measured by R. P. Carithers and W.
      W. Parson [(1976) Biochim. Biophys. Acta 440, 215-232].

PMID- 16592800
TI  - Sizes, locations, and directions of transcription of two genes on a cloned maize
      chloroplast DNA sequence.
AB  - mRNA for the large subunit (LS) of ribulose-1,5-bisphosphate carboxylase [3
      phospho-D-glycerate carboxylase (dimerizing), EC 4.1.1.39] of Zea mays is
      complementary to an uninterrupted 1600-base-pair-long chloroplast DNA sequence
      that has been mapped precisely within the 4350-base-pair-long chloroplast DNA
      fragment Bam 9 to which it had been traced earlier [Bedbrook, J. R., Coen, D. M.,
      Beaton, A. R., Bogorad, L. & Rich, A. (1979) J. Biol. Chem. 254, 905-910]. An
      additional 1400-base-pair-long uninterrupted region that is colinear with a
      chloroplast RNA has been detected on Bam 9. The transcript from this region is
      part of a 2200-nucleotide-long RNA. The remainder of the DNA sequence for the
      2200-base-pair RNA maps outside Bam 9. The 1600-base-pair LS gene and the gene
      for the 2200-nucleotide transcript are close to one another. They are separated
      by an untranscribed intercistronic "gap" about 330 base pairs long. These two
      closely packed genes are inverted on the chromosome-i.e., their 3' termini are at
      opposite ends of the untranscribed gap and they map on opposite strands.

PMID- 16592801
TI  - Isolation and characterization of calmodulin from spinach leaves and in vitro
      translation mixtures.
AB  - Calmodulin, a multifunctional calcium-modulated protein, has been isolated from
      spinach leaf tissue and from spinach leaf messenger RNA translation products. The
      translation protein and the spinach leaf protein have been partially
      characterized and compared to vertebrate calmodulins. Spinach leaf calmodulin
      will quantitatively activate bovine brain phosphodiesterase and will undergo a
      calcium-dependent shift in electrophoretic mobility similar to that of bovine
      brain calmodulin. In the presence of Ca(2+) the spinach and brain proteins
      comigrate, but in the presence of chelators they do not. A polyadenylylated RNA
      fraction has been isolated from spinach leaf tissue and translated in a wheat
      germ cell-free translation system. The calmodulin synthesized in vitro has been
      isolated by using calcium-dependent affinity chromatography on phenothiazine
      Sepharose conjugates. The translation protein comigrates with spinach calmodulin
      during polyacrylamide gel electrophoresis whether in the presence or the absence
      of Ca(2+). The translation protein also undergoes a calcium-dependent mobility
      shift identical to that of spinach calmodulin. Amino acid analysis of the
      translation calmodulin indicates that it does not contain N(epsilon)
      trimethyllysine, an amino acid residue that is characteristic of all calmodulins
      previously examined. These studies suggest that N(epsilon)-trimethyllysine is not
      required for the calcium-dependent interaction of calmodulin with phenothiazines
      and indicate the potential utility of phenothiazine-Sepharose conjugates as
      affinity-based adsorbents in biological and biochemical investigations.

PMID- 16592802
TI  - Cyanobacterial phycobilisomes: Selective dissociation monitored by fluorescence
      and circular dichroism.
AB  - Phycobilisomes are supramolecular assemblies of phycobiliproteins responsible for
      photosynthetic light collection in red algae and cyanobacteria. They can be
      selectively dissociated by reduction of temperature and buffer concentration.
      Phycobilisomes isolated from Fremyella diplosiphon transfer energy collected by C
      phycoerythrin and C-phycocyanin to allophycocyanin. The energy transfer to
      allophycocyanin is nearly abolished at 2 degrees C, as indicated by a blue shift
      in fluorescence emission, and is accompanied by a decrease in the circular
      dichroism in the region of allophycocyanin absorbance. Further dissociation of
      the phycobilisomes can be attained by reduction of buffer concentration and
      holding at 2 degrees C. Energy transfer to C-phycocyanin is nearly abolished, and
      decreases occur in the circular dichroism in the region of C-phycocyanin and C
      phycoerythrin absorbance. Complete dissociation of the phycobilisomes at low
      buffer concentration and 2 degrees C requires extended time. Energy transfer to C
      phycocyanin is further reduced and the circular dichroism maximum of C
      phycoerythrin at 575 nm is lost. Circular dichroism provides information on the
      hexamer-monomer transitions of the phycobiliproteins, whereas fluorescence is
      indicative of hexamer-hexamer interactions. We consider that hydrophobic
      interactions are fundamental to the maintenance of the structure and function of
      phycobilisomes.

PMID- 16592803
TI  - In vitro synthesis of pre-proteins of vacuolar compartmented proteinase
      inhibitors that accumulate in leaves of wounded tomato plants.
AB  - Two proteinase inhibitor proteins that are compartmented in leaf vacuoles
      (lysosomes) were synthesized in vitro. mRNA was isolated from 17-day-old
      expanding tomato leaves by extraction with chaotropic buffers followed by
      chromatography on oligo(dT)-cellulose and was translated with a rabbit
      reticulocyte lysate system. Preparations of mRNA from leaves of both wounded
      plants and unwounded plants directed the incorporation of equivalent amounts of
      label into trichloroacetic acid-precipitable proteins. Only mRNA from leaves of
      wounded plants directed label into proteins that could be immunoprecipitated with
      rabbit IgG specific for either inhibitor I or inhibitor II. These results
      indicate that the wound-induced accumulation of proteinase inhibitors I and II in
      leaf vacuoles is a result of the presence of translatable mRNA species not
      present in leaves of unwounded plants. Gel electrophoresis of the
      immunoprecipitates in NaDodSO(4)/urea/polyacrylamide gels revealed that
      inhibitors I and II were translated in vitro as precursors about 2000 daltons
      larger than the inhibitors found in leaves. The presence of the additional
      polypeptide sequences in the newly synthesized inhibitors indicates that the
      inhibitors are processed either during or after synthesis, and the presequences
      may be signal peptides that are part of the process of inhibitor transport into
      the vacuolar compartments of tomato leaf cells.

PMID- 16592804
TI  - Cell wall appositions and plant disease resistance: Acoustic microscopy of
      papillae that block fungal ingress.
AB  - Plant cells react to localized stress by forming wall appositions outside their
      protoplasts on the inner surface of their cellulose walls. For many years it has
      been inferred that appositions elicited by encroaching fungi, termed "papillae,"
      may subsequently also deter them and thus represent a disease-resistance
      mechanism. Recently, it has been shown that preformed, oversized papillae,
      experimentally produced in coleoptile cells of compatible barley, Hordeum
      vulgare, can completely prevent direct entry of Erysiphe graminis f. sp. hordei
      that ordinarily penetrates and causes disease. To discover how these papillae may
      function, acoustic microscopy was used to contrast their in vivo elastic
      properties with those of ineffective normal papillae and contiguous cell wall.
      Raster and line scans showed intense acoustic activity at sites of preformed
      papillae; scans in selected focal planes identified this activity with the
      papillae, not with subtending cell wall. Minimal acoustic activity was found in
      normal papillae. It is suggested that some wall appositions could serve in
      disease resistance as viscoelastic barriers to mechanical forces exerted by the
      special penetration structures of advancing pathogenic fungi.

PMID- 16592805
TI  - Changes in the abscisic acid content of oat leaves during senescence.
AB  - To investigate the possibility that experimental promotion of retardation of the
      senescence of oat leaves may be mediated by abscisic acid (AbA), determinations
      of AbA were made in leaves senescing under different conditions. The extracts
      were subjected to thin-layer chromatography, the spots were eluted and
      esterified, and the AbA was determined by gas chromatography (overall recovery,
      about 75%). In darkness, where the stomata are closed and senescence is rapid,
      the concentration of AbA increases to at least 5 times its initial value by the
      second day, the time when chlorophyll loss is most rapid. In light, where the
      stomata are open and senescence is very slow, no such increase occurs. But when,
      in light, the stomata are closed by floating the leaves on 1 M mannitol, the AbA
      level again increases to about 5 times the initial value; if the stoma response
      is prevented by kinetin, the increase in AbA is largely suppressed. Similarly,
      phenylmercuric nitrate, at a concentration that closes the stomata, causes a 4
      fold increase in AbA. It is concluded that stomatal closure itself causes AbA
      accumulation and, thus, that AbA may indeed be the proximal cause of leaf
      senescence.

PMID- 16592806
TI  - Ecological and evolutionary significance of mycorrhizal symbioses in vascular
      plants (A Review).
AB  - MYCORRHIZAE, THE SYMBIOSES BETWEEN FUNGI AND PLANT ROOTS, ARE NEARLY UNIVERSAL IN
      TERRESTRIAL PLANTS AND CAN BE CLASSIFIED INTO TWO MAJOR TYPES: endomycorrhizae
      and ectomycorrhizae. About four-fifths of all land plants form endomycorrhizae,
      whereas several groups of trees and shrubs, notably Pinaceae, some Cupressaceae,
      Fagaceae, Betulaceae, Salicaceae, Dipterocarpaceae, and most Myrtaceae form
      ectomycorrhizae. Among legumes, Papilionoideae and Mimosoideae have
      endomycorrhizae and usually form bacterial nodules. The members of the third
      subfamily, Caesalpinioideae, rarely form nodules, and one of the included groups,
      the two large, pantropical, closely related tribes Amherstieae and Detarieae,
      regularly form ectomycorrhizae. Nodules and ectomycorrhizae may well be
      alternative means of supplying organic nitrogen to the plants that form
      them.Those plants having endomycorrhizae usually occur in forests of high species
      richness, whereas those with ectomycorrhizae usually occur in forests of low
      species richness. The roots of ectomycorrhizal trees, however, support a large
      species richness of fungal symbionts, probably amounting to more than 5000
      species worldwide, whereas those of endomycorrhizal trees have low fungal species
      richness, with only about 30 species of fungi known to be involved worldwide.
      Ectomycorrhizal forests are generally temperate or occur on infertile soils in
      the tropics. They apparently have expanded in a series of ecologically important
      events through the course of time from the Middle Cretaceous onward at the
      expense of endomycorrhizal forests.

PMID- 16592807
TI  - Biological competition: Decision rules, pattern formation, and oscillations.
AB  - Competition solves a universal problem about pattern processing by cellular
      systems. Competition allows cells to automatically retune their sensitivity to
      avoid noise and saturation effects. All competitive systems induce decision
      schemes that permit them to be classified. Systems are identified that achieve
      global pattern formation, or decision-making, no matter how their parameters are
      chosen. Oscillations can occur due to contradictions in a system's decision
      scheme. The pattern formation and oscillation results are extreme examples of a
      complementarity principle that seems to hold for competitive systems. Nonlinear
      competitive systems can sometimes appear, to a macroscopic observer, to have
      linear and cooperative properties, although the two types of systems are not
      equivalent. This observation is relevant to theories about the evolutionary
      transition from competitive to cooperative behavior.

PMID- 16592808
TI  - Sex differences in cooperative silk-spinning by weaver ant larvae.
AB  - Final-instar larvae of weaver ants (Oecophylla longinoda) use their silk for nest
      construction rather than for cocoon spinning; this commitment represents a shift
      from entirely selfish to entirely cooperative behavior that occurred after the
      emergence of the phylogenetically advanced subfamily Formicinae. Male larvae were
      found to have smaller silk glands and to contribute substantially less silk to
      nest construction. The hypothesis of kin selection appears to be the most
      plausible and parsimonious explanation of this sex difference, but other,
      individual-level modes of selection have not been eliminated.

PMID- 16592809
TI  - Rotational propensities and identity of bond rupture in 1-cyano-2-methyl-3-(cis
      propenyl) cyclopropanes.
AB  - Comparison of the rate of recemization with the rates of diastereomerization in
      the title compound allows the firm conclusion to be drawn that the theoretically
      weakest of the three cyclopropane bonds is preferentially broken irrespective of
      the multiplicity of the internal rotations involved. Incidentally, the effect of
      an adjacent chiral methyl group on internal rotational propensities is
      elucidated.

PMID- 16592810
TI  - Similarity and differences between conditions for initiation and failure of
      detonation.
AB  - A theory is proposed to study the sensitivity of cylindrical explosives. Using
      the equations governing the conservation of mass, energy, and momentum, the
      equation of state, and Newtonian mechanics, we have derived the expression D =
      D(o)e(-a2/d), in which the apparent length of the reaction zone, a, takes into
      account burned and unburned explosive and pressure release through the back and
      sides of the reaction zone. D is the detonation velocity and d is the diameter of
      the cylindrical charge. From the observed D(1/d) curves and critical energy
      values, we can interpret failure and other phenomena associated with detonation.

PMID- 16592812
TI  - Very low energy cross sections for collision-induced rotational relaxation of
      I(2) seeded in a supersonic free jet.
AB  - We report a study of rotational relaxation of I(2) seeded in He, Ne, and Ar free
      jets. It is inferred that in the very low collision energy range covered by these
      experiments the cross section for rotational relaxation is independent of energy.

PMID- 16592811
TI  - Lipid-protein interaction in the glycophorin-dipalmitoylphosphatidylcholine
      system: Raman spectroscopic investigation.
AB  - Raman spectra have been recorded as a function of temperature for lipid-protein
      complexes of glycophorin isolated from erythrocyte membranes reconstituted with
      dipalmitoylphosphatidylcholine (DPPC) and its chain perdeuterated analogue
      ([(2)H(62)]DPPC). The conformation of the phospholipid hydrocarbon chains in the
      vicinity of protein is drastically altered from that in pure lipid dispersions.
      Analysis of the chain C-(2)H stretching vibrations for complexes of [(2)H(62)]
      DPPC-glycophorin shows that at lipid:protein mole ratios of 125:1, a broad
      melting event occurs that is not observable by calorimetric techniques. The
      midpoint occurs at temperatures about 15 degrees C below that of the gel/liquid
      crystal phase transition for [(2)H(62)]DPPC in multilamellar dispersions. The
      same number of gauche rotamers form in the phospholipid hydrocarbon chains during
      the melting process as in the phase transition of the unperturbed molecule.
      Analysis of the C-H stretching region of the Raman spectrum in DPPC-glycophorin
      complexes indicates that lateral interactions between phospholipid chains in the
      complex are reduced so that interchain vibrational coupling is minimized. The
      observed differences between the Raman melting curves and the calorimetric
      endothermic transitions arise because different populations of phospholipid
      molecules are sampled in the two experiments. The advantages of Raman
      spectroscopy for the study of lipid-protein interaction are demonstrated in the
      current work. Implications for the structure of the lipid in the immediate
      vicinity of membrane protein are discussed.

PMID- 16592813
TI  - 2,3-trans-3,4-trans-3,4-Dihydroxy-L-proline: An amino acid in toxic peptides of
      Amanita virosa mushrooms.
AB  - Among the four possible stereoisomers of 3,4-dihydroxy-L-proline,2,3-trans-3,4
      trans-3,4-dihydroxy-L-proline (IV) had not been found in nature previously. It
      has now been detected as a component of virotoxins, toxic peptides of Amanita
      virosa mushrooms. Because periodate failed to effect an oxidative glycol
      splitting reaction, the two hydroxyl groups in positions 3 and 4 were expected to
      be in a trans configuration. Furthermore, the formation of a 4-lactone on
      treatment with acids pointed to the carboxyl group and the hydroxyl group at
      position 4 being in a cis configuration. These results are in agreement with
      structure IV only. Final proof for structure IV was given by NMR spectroscopy and
      direct comparison with the 2,3-cis-3,4-trans-3,4-dihydroxy-L-proline isomer.

PMID- 16592814
TI  - Asymmetry of interoceanic fresh-water and heat fluxes.
AB  - According to recent hydrological and meteorological studies, the meridional flux
      of fresh water and heat is remarkably different from ocean to ocean. These fluxes
      have been found to be consistent with the temperature and salinity distribution
      in the northern hemisphere. However, an attempt to map these fluxes on the
      temperature-salinity plane of a southern latitude leads to such large amplitudes
      of water-mass volume flux that it seems that there may be something wrong about
      them.

PMID- 16592815
TI  - Estimation and prediction for mixtures of the exponential distribution.
AB  - Let x be a random variable whose distribution is an unknown mixture of
      exponentials with different means theta. From a random sample x(1),...,x(n) of x
      values we show that E(thetax > a) can be estimated for any given a > 0. We can
      therefore predict the average of all future observations taken on those x values
      in the sample that exceed a.

PMID- 16592816
TI  - A suggestion for naming faces of ring compounds.
AB  - Discussion of the topology of interaction of ring compounds with macromolecules
      and receptors requires a system for naming the faces of the cyclic compound. An
      alpha/beta-face nomenclature is suggested that is based on the
      clockwise/counterclockwise direction of ascending numbering in the ring with the
      lowest numbered unshared ring atom. This system is applicable to a very broad
      range of compounds: sugars, cyclic bases, steroids, cyclitols, porphyrins, etc.,
      and molecules with a single ring, fused rings, encompassing rings, and rings
      formed by head-to-tail polymerization.

PMID- 16592817
TI  - "Living electrode" as a long-lived photoconverter for biophotolysis of water.
AB  - Living blue-green algae (Mastigocladus laminosus), immobilized on an SnO(2)
      optically transparent electrode with calcium alginate, functioned as an anodic
      photoelectrode on continuous illumination for periods of time adequate for use in
      a conventional electrochemical cell. This "living electrode" shows promise of use
      as a long-lived photoconverter of solar radiant energy to electric energy and as
      a suitable replacement for unstable chloroplast systems.

PMID- 16592818
TI  - Localization of the amino acid substitution site in a new variant of human serum
      albumin, albumin Mexico-2.
AB  - Using an electrophoretic screening procedure, we have discovered that two species
      of human serum albumin Mexico occur that are indistinguishable by conventional
      electrophoretic methods. We suggest that these species be referred to as albumins
      Mexico-1 and Mexico-2. Isolation and determination of the partial sequence of the
      cyanogen bromide fragment of albumin Mexico-2 that differs from the corresponding
      fragment of the common albumin A revealed this variant to arise from at least a
      glycine/aspartic acid substitution at position 550. This region of the albumin
      molecule is involved in the binding of the fatty acid, palmitate.

PMID- 16592819
TI  - Proteins encoded by Agrobacterium tumefaciens Ti plasmid DNA (T-DNA) in crown
      gall tumors.
AB  - In order to detect proteins that may be produced in crown gall tumors as a result
      of expression of incorporated Agrobacterium tumefaciens Ti plasmid DNA (T-DNA),
      we have isolated mRNA complementary to T-DNA and translated this in a protein
      synthesizing system derived from wheat germ. mRNA prepared from cultured E1 tumor
      from Nicotiana tabacum hybridized with HindIII fragment 1 sequences of T-DNA
      immobilized on cellulose nitrate filters. Two proteins of 30,000 and 16,500 M(r)
      were produced when this selected RNA was released and translated. Other tumor
      lines from N. tabacum were investigated, and a protein of slightly less than
      30,000 M(r) was encoded by HindIII fragment 1 sequences of 15955/01 tumor. No
      products were observed for 15955/1 tumor line, which differs from E1/B6-806 and
      15955/01 in that it does not produce octopine. mRNA species of each of the tumor
      lines hybridized to Bst I fragment 8 sequences of T-DNA and produced a common
      protein of 15,000 M(r). Because this protein is derived from the region of the T
      DNA that is conserved in octopine- and nopaline-type crown gall tumors, it may
      play a role in oncogenicity.

PMID- 16592820
TI  - Contrasts between oxygenic and anoxygenic photoreduction of ferredoxin:
      Incompatibilities with prevailing concepts of photosynthetic electron transport.
AB  - An investigation by paramagnetic resonance spectroscopy of the photoreduction of
      ferredoxin, oxygenically by water and anoxygenically by a direct electron donor
      to photosystem I, led to the unexpected findings that different reductive
      mechanisms may be involved. Ferredoxin photoreduced by water was not reoxidized
      in the light under aerobic conditions and, under anaerobic conditions, it was
      remarkably resistant to reoxidation in the dark. By contrast, ferredoxin
      photoreduced by a donor to photosystem I was readily reoxidized in the light by
      air and, under anaerobic conditions, by exposure to darkness. Furthermore, when
      electron transport linking photosystems I and II was inhibited by a plastoquinone
      antagonist, ferredoxin was photoreduced by water with no evidence for an
      accompanying photoreduction of the more electronegative bound iron-sulfur centers
      in chloroplasts. These findings are at variance with the now prevalent concepts
      of photosynthetic electron transport.

PMID- 16592821
TI  - Photorespiration mutants of Arabidopsis thaliana deficient in serine-glyoxylate
      aminotransferase activity.
AB  - Three mutants of the crucifer Arabidopsis thaliana (Linnaeus) Heynhold were
      isolated that are completely lacking in activity catalyzed by serine-glyoxylate
      aminotransferase (EC 2.6.1.45), a peroxisomal enzyme involved in photorespiratory
      carbon metabolism. These mutants were viable and exhibited normal photosynthesis
      under conditions that suppressed photorespiration, but they were inviable and
      photosynthesized at greatly reduced rates under conditions that promoted
      photorespiration. Serine and glycine accumulated as end products of
      photosynthesis in the mutants, mostly at the expense of starch and sucrose. The
      mutants are allelic, and the segregation patterns of plant viability,
      photosynthetic activity, and enzyme activity in the F(1) and F(2) generations
      indicated that all the observed effects were caused by a single recessive nuclear
      mutation. This conclusion was confirmed by the isolation of seven revertants in
      which viability, photosynthetic capacity, and enzyme activity were simultaneously
      restored. Mutants of the type described here, in which photorespiration is
      changed from a merely wasteful process into one that is lethal, may permit the
      direct selection of secondary mutations that reduce photorespiration.

PMID- 16592822
TI  - Plasmid-dependent temperature-sensitive phase in crown gall tumorigenesis.
AB  - Two methods have been used to show that the temperature-sensitive (ts) genes for
      plasmid maintenance located on pTiC58 are responsible for the presence of a
      specific 37 degrees C ts period during crown gall tumorigenesis. Tumors induced
      by Agrobacterium tumefaciens strain C58 become resistant to 32 degrees C by 96 hr
      after infection, indicating that the "inception phase" of crown gall is complete
      at that time. However, C58 tumors remain sensitive to 37 degrees C until 168 hr
      after infection. When pTiC58 is replaced in strain C58 by a plasmid that is
      temperature resistant for maintenance within the bacterium at 37 degrees C
      (B(6)806) the tumors induced by the new strain (A277) become resistant to 37
      degrees C by 96 hr after infection. Furthermore, when pTiC58 is selected for
      temperature resistance in strain C58 at 37 degrees C, the tumors induced by the
      new strain, C58(TR), become resistant to 37 degrees C approximately 40 hr earlier
      than do tumors induced by the parent strain C58. These results prove that the 37
      degrees C ts period (96-168 hr after infection) is coded for ts plasmid
      maintenance genes located on pTiC58. Incorporation of [(3)H]-thymidine into
      pTiC58 in strain C58 is specifically inhibited at 37 degrees C compared to
      chromosomal DNA and is not inhibited at 32 degrees C. The data presented support
      a mechanism in which the 37 degrees C, ts period between 96 and 168 hr after
      infection is due to the requirement for the plasmid-coded maintenance genes
      involved in plasmid replication within incipient tumor cells. The fact that the
      37 degrees C ts period ends after 168 hr indicates a transient requirement for
      the ts gene product, perhaps due to the stable integration of plasmid DNA into
      plant genetic elements by that time.

PMID- 16592823
TI  - Agropine in "null-type" crown gall tumors: Evidence for generality of the opine
      concept.
AB  - Agrobacterium Ti (tumor-inducing) plasmids, the causative agents of crown gall
      disease, fall into four genetic groups based on the patterns of octopine and
      nopaline synthesis (by crown gall tumors) and catabolism (by Agrobacterium
      tumefaciens) for which they are responsible. Two classes of Ti plasmids induce
      tumors that synthesize neither octopine nor nopaline. The existence of these Ti
      plasmids challenged the view that opines such as octopine and nopaline play a
      central role in crown gall biology. We now report the occurrence of an opine in
      tumors induced by one of these classes of Ti plasmids, the "null-type" plasmids
      typified by pTi Bo542. The opine was purified by biological enrichment based on
      its utilization by bacteria containing pTi Bo542 but not by bacteria lacking a Ti
      plasmid. The mass spectrum and biological properties of this opine are identical
      to those of agropine, an opine recently discovered in octopine-type tumors. We
      propose that null-type Ti plasmids now be named for their signal opine, agropine
      type Ti plasmids.

PMID- 16592824
TI  - One-sided difference schemes and transonic flow.
AB  - Two one-sided conservation form difference approximations to a scalar one
      dimensional convex conservation law are introduced. These are respectively of
      first- and second-order accuracy and each has the minimum possible band-width.
      They are nonlinearly stable, they converge only to solutions satisfying the
      entropy condition, and they have sharp monotone profiles. No such stable
      approximation of order higher than two is possible. Dimensional splitting
      algorithms are constructed and used to approximate the small-disturbance equation
      of transonic flow. These approximations are also nonlinearly stable and without
      nonphysical limit solutions.

PMID- 16592825
TI  - Stationary spiral flow in polytropic stellar models.
AB  - It is shown that, in addition to the static Emden solution, a self-gravitating
      polytropic gas has a dynamic option in which there is stationary flow along
      spiral trajectories wound around the surfaces of concentric tori. The motion is
      obtained as a solution of a partial differential equation which is satisfied by
      the meridional stream function, coupled with Poisson's equation and a Bernoulli
      type equation for the pressure (density). The pressure is affected by the whole
      of the Bernoulli term rather than by the centrifugal part only, which acts for a
      rotating model, and it may be reduced down to zero at the center. The spiral type
      of flow is illustrated for an incompressible fluid (n = 0), for which an exact
      solution is obtained. The features of the dynamic constant-density model are
      discussed as a basis for future comparison with the solution for compressible
      models.

PMID- 16592826
TI  - The x-ray luminosity-redshift relationship of quasars.
AB  - Chronometric cosmology provides an excellent fit for the phenomenological x-ray
      luminosity-redshift relationship for 49 quasars observed by the Einstein
      satellite. Analysis of the data on the basis of the Friedmann cosmology leads to
      a correlation of absolute x-ray luminosity with redshift of >0.8, which is
      increased to approximately 1 in the bright envelope. Although the trend might be
      ascribed a priori to an observational magnitude bias, it persists after
      nonparametric, maximum-likelihood removal of this bias.

PMID- 16592827
TI  - Relative binding affinities of monovalent cations for double-stranded DNA.
AB  - The competition between sodium and various other monovalent cations that bind to
      helical DNA in aqueous solution has been studied by (23)Na NMR. Variations in the
      sodium linewidth with the concentration of the other ion have been analyzed with
      an equation that describes the competitive binding in terms of two parameters: r,
      the total extent of counterion binding, and D, a measure of the binding affinity
      of a cation relative to sodium. The concentration dependence of these parameters
      was found to be minimal. In the absence of a competing cation the constancy of r
      has been demonstrated over a range of DNA phosphate concentrations (0.0025-0.015
      M) and NaCl concentrations (0.003-1.3 M). For the cations investigated the range
      in D values is small (0.5-0.9), and the relative binding affinities follow the
      order: NH(4) (+) > Cs(+) > K(+) > Li(+) > Na(+).

PMID- 16592828
TI  - Mechanism of thermal rearrangement of the spiro bicyclo[2.1.0]-pentane-5,2'
      methylenecyclopropanes to 6- and 7- methylenebicyclo[3.2.0]hept-1-enes.
AB  - The thermal rearrangements of the bicyclo[2.1.0]pentane-5,2'
      methylenecyclopropanes fall into two classes. The first occurs near 80 degrees C
      and consists of a double epimerization ("bridge flip") which is initiated by
      cleavage of the bridge bond. An alternative mechanism by way of a
      trimethylenemethane intermediate is ruled out by an isotopic position-marking
      experiment. The second rearrangement begins to be detected above 120 degrees C.
      It gives the isomeric 6- and 7-methylenebicyclo[3.2.0]hept-1-enes. Two possible
      mechanisms can operate in this complex change, but a choice between them is not
      yet possible.

PMID- 16592829
TI  - Benzoate catalysis in the hydrolysis of endo-5-[4'(5')imidazolyl]
      bicyclo[2.2.1]hept-endo- 2-yl trans-cinnamate: Implications for the charge
      transfer mechanism of catalysis by serine proteases.
AB  - The acceleration, by a factor of 2500, of the hydrolysis of endo-5
      [4'(5')imidazolyl]bicyclo[2.2.1]hept-endo- 2-yl trans-cinnamate by 0.5 M sodium
      benzoate in 42 mol% dioxane in water can be explained without resort to operation
      of a "charge-relay" mechanism similar to that often postulated to account for the
      enzymatic activity of serine proteases. The degree of ionization of 4
      methylimidazole and of sodium benzoate in 42 mol% dioxane in water at 60 degrees
      C have been measured by NMR spectroscopy.

PMID- 16592830
TI  - Dielectric constant of atomic fluids with variable polarizability.
AB  - The Clausius-Mossotti function for the dielectric constant is expanded in terms
      of single atom and pair polarizabilities, leading to contributions that depend on
      both the trace and the anisotropy of the pair-polarizability tensor. The short
      range contribution of the anisotropic part to the pair polarizabilities has
      previously been obtained empirically from light scattering experiments, whereas
      the trace contribution is now empirically determined by comparison to dielectric
      experiments. For helium, the short-range trace part agrees well with electronic
      structure calculations, whereas for argon qualitative agreement is achieved.

PMID- 16592831
TI  - Phase equilibria for highly unsymmetrical plasmas and electrolytes.
AB  - The conclusion of classical Debye-Huckel theory that a phase separation may occur
      in highly unsymmetrical plasmas or electrolytes is shown to be false and to arise
      from a serious error in the treatment of the interaction of pairs of the most
      highly charged ions. After an approximate correction for this error, no phase
      separation is predicted. Specific application to iron in the solar plasmas is
      discussed.

PMID- 16592832
TI  - Role of the chlorophyll dimer in bacterial photosynthesis.
AB  - The role of a special dimer (D) of bacteriochlorophyll molecules in bacterial
      photosynthesis was examined by calculations of the rates of electron transfer
      reactions in a system of the dimer and a bacteriopheophytin (BPh) molecule. It
      was found that the dependence of the potential surfaces of D on the distance
      between the monomers allows a fast light-induced electron transfer from D to BPh
      but only a slow back reaction (reduction of D(+) by BPh(-)). The same potential
      surfaces allow efficient reduction of D(+) by cytochrome c. Possible advantages
      of greatly different values of the electronic matrix elements for the forward and
      back reactions are pointed out. It is suggested that the electrostatic
      interaction between D(+) and an ionized group of the protein might play an
      important role in the photosynthetic reaction.

PMID- 16592833
TI  - Femtosecond relaxation of an iron porphyrin observed with polarization
      spectroscopy in a three-level system.
AB  - An experimental and theoretical study is presented of the nonlinear response of a
      dilute solution being pumped by two laser fields having different frequencies
      omega(1) and omega(2) that are both in resonance with electronic transitions of
      the solute. Experimental results were obtained for the dispersion of the third
      order susceptibility chi((3))(omega(2))(2) for a dilute solution of iron(III)
      tetraphenylporphyrin chloride in chloroform with a fixed intense field (omega(1))
      resonant with the Q(o) transition and a tunable weaker field (omega(2)) resonant
      with the Soret transition. The observed Lorentzian dispersion is slightly
      narrower than the linear absorption spectrum. The theoretical model for the third
      order polarization incorporates three levels coupled to two electromagnetic
      fields and a population reservoir. The equations of motion for the density
      operator were solved in third order for the appropriate Fourier component. The
      resulting dispersion curve depends on both total dephasing and population decay
      rates, thereby demonstrating a general method for the determination of
      subpicosecond relaxation processes in systems to which the model is applicable.
      Theoretical fits to the results for iron(III) tetraphenylporphyrin chloride imply
      that the Soret transition is essentially homogeneously broadened with a total
      dephasing width of 900 +/- 200 cm(-1), and it is argued that the population decay
      time in this case is approximately 3.5 fsec. The broad linear absorption spectrum
      of the Soret band is interpreted as resulting from intramolecular perturbations
      between the Soret and lower energy excited states of iron(III)
      tetraphenylporphyrin chloride.

PMID- 16592834
TI  - Interphases of chain molecules: Monolayers and lipid bilayer membranes.
AB  - Using the lattice model for a liquid, we treat the packing of short-chain
      molecules in interphases such as bilayer membranes. The constant density in the
      interphase imposes intermolecular constraints on the configurations of the
      flexible chains. The statistical theory here presented predicts a diffuse
      distribution of chain ends near the bilayer midplane; no adjustable parameters
      are required. Inasmuch as some of the chains terminate relatively near the polar
      interface, the number of chains reaching deeper planar layers is diminished.
      Consequently, configurational freedom increases with depth. This is the source of
      the well-known disorder gradient.

PMID- 16592835
TI  - Bounds for the rth characteristic frequency of a beaded string or of an
      electrical filter.
AB  - The fundamental mode of vibration of a beaded string has a shape without change
      of sign. The rth higher normal mode of vibration has r changes of sign. Given any
      virtual shape of the string with r changes of sign, an algorithm is found that
      gives upper and lower bounds for the rth characteristic frequency as a function
      of the virtual shape. By making a certain transformation it is found that this
      algorithm holds for the characteristic frequencies of an inductor-capacitor
      network. Other transformations show that it applies to the rth eigenvalue of a
      Hermitian matrix.

PMID- 16592836
TI  - Threefolds whose canonical bundles are not numerically effective.
AB  - Let X be an arbitrary nonsingular projective 3-fold whose canonical bundle is not
      numerically effective. Then we have: (i) X contains an exceptional divisor of
      several types, which we classify explicitly, (ii) X has a morphism to a
      projective nonsingular surface whose fibers are conics, (iii) X has a morphism to
      a projective nonsingular curve whose general fibers are Del Pezzo surfaces, or
      (iv) X is a Fano 3-fold with Picard number 1.

PMID- 16592837
TI  - Internal supersymmetry and unification.
AB  - We construct a family of finite-dimensional representations of the superalgebra
      sl(n/m) that depend on an integer parameter for m > 1 and on a complex parameter,
      b, for m = 1. We describe some models of elementary particles for sl(2/1),
      sl(3/1), and sl(5/1). This involves the choice of the parameter b and the choice
      of the operators I(3) (the third component of the weak left-handed isospin) and U
      (the weak hypercharge). These must commute, and are related to the electric
      charge by the usual formula Q = I(3) + (1/2)U. In particular, taking I(3) to be
      in its standard form in su(2) subset sl(5) subset sl(5/1) and requiring that U
      commute with color su(3) subset sl(5) subset sl(5/1) leaves three free
      parameters, two for the choice of U and one for the choice of b. We show that
      there are just two possible choices of these parameters yielding exactly all 32
      quark and lepton charges: the Georgi-Glashow U in su(5), corresponding to U(1,
      (2/3)) and arbitrary b and U(0,(1/3)) negated set membership su(5), with b = 2.
      We provide a general construction of representations of sl(n/1) consisting
      exactly of sequences of generations of quarks and leptons.

PMID- 16592838
TI  - Ternary transition metal phosphides: High-temperature superconductors.
AB  - Two systems of ternary transition metal phosphides with the ordered Fe(2)P-type
      hexagonal structure are reported. They have the general formula MRuP and MOsP, in
      which M can be Ti, Zr, or Hf. An onset of the superconducting transition
      temperature as high as 13.0 K is reported for the ZrRuP compound.

PMID- 16592839
TI  - Sequential medical trials.
AB  - A model for sequential clinical trials is discussed. Three proposed stopping
      rules are studied by the Monte Carlo method for small patient horizons and
      mathematically for large patient horizons. They are shown to be about equally
      effective and asymptotically optimal from both Bayesian and frequentist points of
      view and are markedly superior to any fixed sample size procedure.

PMID- 16592840
TI  - Calculations of the circular dichroism of adenosine derivatives constrained in
      the syn form.
AB  - The rotational strengths of the four longer wavelength transitions, B(2u), B(1u),
      and the two E(1u), of adenosine derivatives constrained in the syn form have been
      investigated theoretically and experimentally. The theory combines a complete
      neglect of differential overlap version S (CNDO/S) description of the base with a
      generalized bond exciton method by means of a matrix method. Rotational strength
      wheels for these transitions showing the rotational strength as a function of the
      glycosidic rotational angles are presented and sector rules discussed. Similar
      sector rules are predicted for purine nucleoside derivatives containing the 6
      amino substituent, regardless of heteroatom content at positions 1 or 3 of the
      base. The sector rules for the B(2u) rotational strength of purine nucleosides
      lacking the 6-amino substituent are strongly influenced by aza substitution. The
      circular dichroism spectra of 3-deazaadenosine, 8-(alpha-hydroxyisopropyl)
      adenosine, and other purine nucleosides having a strong preference for the syn
      conformation are presented and compared with the theoretical results.

PMID- 16592841
TI  - cis-4-Cyclohexene-1,2-dicarboximide: Inhibitor of phytochrome-promoted seed
      germination.
AB  - cis-4-Cyclohexene-1,2-dicarboximide (CHDC) inhibits the germination of light
      requiring seeds in both light and darkness but has no effect upon the germination
      of non-light-requiring seeds. In lettuce seeds, CHDC inhibits the action of far
      red-absorbing form of phytochrome in breaking dormancy. This inhibition can be
      overcome by benzyladenine and red light together, but not by a combination of red
      light and gibberellic acid. Gibberellic acid-induced germination of lettuce seeds
      in darkness is inhibited also by CHDC. Embryos isolated from dark-imbibed lettuce
      seeds germinate on the inhibitor. CHDC was thought to be an "analogue" of
      cycloheximide, but it does not inhibit protein synthesis in lettuce seeds. Our
      results lead us to conclude that CHDC inhibits germination of seeds that require
      red light to break dormancy and interferes with some aspect of metabolism that is
      stimulated by far-red-absorbing form of phytochrome.

PMID- 16592843
TI  - Convexity properties of products of random nonnegative matrices.
AB  - Consider a sequence of N x N random nonnegative matrices in which each element
      depends on a vector u of parameters. The nth partial product is the random matrix
      formed by multiplying, from right to left, the first n of these random matrices
      in order. Under certain conditions, the elements of the nth partial product grow
      asymptotically exponentially as n increases, and the logarithms of the discrete
      long-run growth rates are convex functions of u. These conditions are met by some
      models in statistical mechanics and demography. Consequently, the Helmholtz free
      energy is concave and the population growth rate is convex in these models.

PMID- 16592842
TI  - Metabolic resource allocation vs. mating attractiveness: Adaptive pressures on
      the "alba" polymorphism of Colias butterflies.
AB  - The sex-limited "alba" genetic polymorphism in wing color of Colias butterflies
      has been studied with respect to potential selective pressures on this locus.
      Alba female pupae, carrying at least one dominant A allele, redirect resources,
      used by aa pupae for pigmentation, to other metabolic ends. Associated with this
      reallocation, alba, A-, female adults eclose earlier, retain more larva-derived
      resources in their fat bodies for somatic maintenance and for reproduction, and,
      in some conditions, mature their eggs faster than do aa females. Alba females are
      also less attractive to males than are aa females and mate less frequently.
      Evolutionary implications of these results are discussed.

PMID- 16592844
TI  - Comment on the rotational state dependence of indirect photodissociation of a
      polyatomic molecule.
AB  - The rotational state dependence of indirect photodissociation has been examined
      in the light of some recent developments in the theory of radiationless
      transitions in rotating molecules. A simple argument based on projection
      operators leads to the prediction of sequential kinetics from an initial singlet
      state through an intermediate triplet bound state and on to a final dissociative
      state. The results indicate that as long as the geometry of the molecule in the
      triplet state is not very different from that of the singlet state, only a very
      small rotational dependence will show up in the singlet state radiationless
      lifetime, in spite of the fact that the overall dissociation constitutes a large
      geometry change.

PMID- 16592845
TI  - Collinearity-preserving functions between Desarguesian planes.
AB  - Using concepts from valuation theory, we obtain a characterization of all
      collinearity-preserving functions from one affine or projective Desarguesian
      plane into another. The case in which the planes are projective and the range
      contains a quadrangle has been treated previously in the literature. Our results
      permit one or both planes to be affine and include cases in which the range
      contains a triangle but no quadrangle. A key theorem is that, with the exception
      of certain embeddings defined on planes of order 2 and 3, every collinearity
      preserving function from one affine Desarguesian plane into another can be
      extended to a collinearity-preserving function between enveloping projective
      planes.

PMID- 16592846
TI  - Field-induced trapping as a probe of dimensionality in molecular crystals.
AB  - The combined effect of an electric field and reduced dimensionality on the
      hopping motion of a charge carrier in an anisotropic molecular crystal is
      determined. New, exact expressions for S(t), the number of distinct sites
      occupied by a carrier in time t, are presented for two-dimensional and three
      dimensional anisotropic lattices. The general results are used to model the
      unusual phenomenon of field-induced charge carrier trapping reported to occur in
      a quasi-one-dimensional molecular crystal. An analytic expression for the carrier
      lifetime tau, as a function of the anisotropy in the molecular hopping rates and
      electric field, is developed and is shown to be in excellent agreement with
      experimental results. A major conclusion of the theory is that E(c), the electric
      field characterizing the E dependence of tau, can be a more direct probe of the
      intrinsic anisotropy than is the observed mobility ratio.

PMID- 16592847
TI  - The "excess entropy" around nonequilibrium steady states, (deltaS)(ss), is not a
      Liapunov function.
AB  - In a response to my recent paper [Fox, R. F. (1979) Proc. Natl. Acad. Sci. USA
      76, 2114-2117], Nicolis and Prigogine [Nicolis, G. & Prigogine, I. (1979) Proc.
      Natl. Acad. Sci. USA 76, 6060-6061] reasserted that the "excess entropy" around
      nonequilibrium steady states, (delta(2)S)(ss), is a Liapunov function. A simple,
      explicit counterexample which invalidates this claim is presented. The existence
      of an alternative theory possessing a proper Liapunov function for steady states
      is reviewed.

PMID- 16592848
TI  - Application of the Eyring-Stover survival theory to soil-related functions.
AB  - The fit of the Eyring-Stover statistical survival theory was found to be precise
      when applied to diverse soil-related functions.

PMID- 16592849
TI  - Cucurbitacins as kairomones for diabroticite beetles.
AB  - The characteristic bitter substances of the Cucurbitaceae act as kairomones for a
      large group of diabroticite beetles (Chrysomelidae, Galerucinae, Luperini),
      promoting host selection and compulsive feeding behavior. These beetles (e.g.,
      Diabrotica undecimpunctata howardi) respond to as little as 1 ng of cucurbitacin
      (Cuc) B on thin-layer plates by arrest and compulsive feeding. Six species of
      diabroticite beetles were about 10 times more responsive to Cuc B than to Cuc E
      and less responsive to Cuc D, I, and L. Chloroform extracts of 18 species of
      Cucurbita were developed on thin-layer chromatograms and exposed to diabroticite
      beetles. The feeding patterns showed pronounced beetle responses to three general
      Cuc distribution patterns: Cuc B and D as in Cucurbita andreana and C.
      ecuadorensis; Cuc E and I as in C. okeechobeensis and C. martinezii; and Cuc E
      glycoside in C. texana. All the diabroticites responded in exactly the same
      feeding patterns. The results demonstrate a coevolutionary association between
      the Cucurbitaceae and the Luperini, during which the intensely bitter and toxic
      Cucs that arose to repel herbivores and protect the plants from attack became
      specific kairomone feeding stimulants for the beetles.

PMID- 16592850
TI  - T-DNA from Agrobacterium Ti plasmid is in the nuclear DNA fraction of crown gall
      tumor cells.
AB  - The crown gall teratoma tumor line BT37, incited by Agrobacterium tumefaciens
      strain T37, has been found to contain part of the tumor-inducing plasmid, pTi
      T37, of the inciting strain. This foreign DNA segment, called T-DNA, is
      maintained at several copies per diploid tumor cell. We have examined subcellular
      DNA fractions from this tumor line in an effort to determine whether T-DNA is in
      chloroplasts, mitochondria, or nuclei. Tumor cell chloroplast DNA exhibited EcoRI
      and Bst I endonuclease cleavage patterns identical to those of normal tobacco
      chloroplast DNA. Tumor cell mitochondrial DNA exhibited a complex Bst I cleavage
      pattern that did not differ detectably from that of normal tobacco mitochondrial
      DNA. Southern blots of tumor chloroplast and mitochondrial cleavage products did
      not hybridize with labeled pTi T37 DNA, whereas blots of tumor cell nuclear DNA
      cleavage products hybridized strongly. We conclude that T-DNA is located not in
      chloroplasts or mitochondria but rather in the nuclear fraction of this tumor
      line.

PMID- 16592851
TI  - Resource variation and the structure of British bird communities.
AB  - Data on the foraging microhabitats of British birds are reanalyzed with the aim
      of understanding how fluctuations in resource abundance affect niche
      relationships and community structure. At Marley Wood, overlap in the foraging
      sites of resident bird species increased during the late spring and summer and
      decreased during the fall and winter. Among bird species coexisting in the pine
      forests at Thetford Chase, spatial overlap and spatial niche widths were
      positively correlated with food abundance over a 4-year period. These results
      suggest that in variable environments similarity in spatial niches is an inverse
      function of the intensity of competition for food. As food supplies drop,
      consumer species must apparently occupy increasingly different foraging areas in
      order to coexist. In less variable environments, however, resource stability may
      allow finer partitioning of the available foraging space and greater spatial
      overlap within a given foraging area. The results of this paper also suggest a
      reinterpretation of MacArthur's study of resource partitioning among warbler
      species in the boreal forests of New England. Rather than providing an instance
      of niche segregation in order to avoid intense competition, MacArthur's warblers
      may actually represent another example of increased spatial similarity when food
      resources are abundant and competition is reduced.

PMID- 16592852
TI  - Translation of epigenetic rules of individual behavior into ethnographic
      patterns.
AB  - The pivotal process in gene-culture coevolution is envisaged to be the evolution
      of behavioral epigenesis. From premises based on the known properties of
      enculturation and usage diffusion within societies, a probabilistic model is
      constructed to estimate the degree to which rules governing individual
      development canalize ethnographic curves (the probability density distributions
      of societies engaged in varying patterns of usage). The results indicate that
      under most conceivable conditions the translation from individual epigenesis to
      social pattern is amplified, to an extent that differences in bias too faint to
      be detected in ordinary developmental studies can generate conspicuous variation
      in the ethnographic curves. Examples are cited of sufficiently biased epigenesis
      in human behavior.

PMID- 16592853
TI  - Asymptotic form for random walk survival probabilities on three-dimensional
      lattices with traps.
AB  - The problem of calculating statistics of time-to-trapping of a random walker on a
      trap-filled lattice is of interest in solid state physics. Several authors have
      suggested approximate methods for calculating the average survival probabilities.
      Here, an exact asymptotic form for the probability that an n step random walk
      visits S(n) distinct sites is used to ascertain the validity of a simple
      approximation suggested by Rosenstock. For trap concentrations below 0.05, the
      relative error in using Rosenstock's approximation is less than 10%.

PMID- 16592854
TI  - Backlund transformations for multidimensional sine-Gordon equations.
AB  - A class of Backlund transformations for multidimensional sine-Gordon equations is
      shown to relate solutions of only one- and two-dimensional equations. Also, a
      proposed superposition principle is shown to be useless.

PMID- 16592855
TI  - Boundary methods: A criterion for completeness.
AB  - The application of methods which constitute an alternative to boundary integral
      equations to specific problems depends on development of complete systems of
      solutions, convergence of approximating procedures, and formulation of
      variational principles. This paper establishes a criterion for completeness. In
      this manner, greater flexibility of the theory is achieved; for example, systems
      of functions which are complete for different types of boundary conditions are
      developed.

PMID- 16592856
TI  - Temperature and pressure dependence of viscosity of quantum liquid He according
      to significant structure theory.
AB  - Both solid-like and gas-like flow structures are considered in the calculation of
      viscosity of liquid (4)He using the significant structure theory of liquids. The
      predominance of quantum mechanical zero-point motion over that arising from
      thermal excitation is taken into account for the solid-like motion of molecules.
      The viscosity of liquid (4)He under its own vapor pressure calculated over its
      whole temperature range is in reasonably good agreement with experimental data.
      The pressure dependence of viscosity also was obtained. The calculation does not
      yield good results at high densities where the free jumping of molecules into the
      nearest neighboring vacancies through the kinetic zero-point motion is no longer
      plausible.

PMID- 16592857
TI  - Asymptotic behavior of atomic and molecular wave functions.
AB  - The asymptotic form of bound-state wave functions is derived by analytic
      continuation of asymptotic scattering-state wave functions. The result is also
      regorously derived by using an approach that is independent of scattering theory.
      One aspect of the result is that the N electron wave function becomes the lowest
      accessible exact wave function for the remaining N - 1 electrons when one
      electron is far away from all the nuclei. This shows that the recently developed
      extended Koopmans' procedures are in principle exact for the first ionization
      energy.

PMID- 16592858
TI  - Neuroendocrine regulation of corpus allatum activity in Manduca sexta: Sequential
      neurohormonal and nervous inhibition in the last-instar larva.
AB  - The inactivation of corpora allata (CA) in the last-instar larva of the tobacco
      hornworm Manduca sexta was studied using in vivo assay methods that test the
      capacity of the glands to induce an extra larval molt. Results indicate that the
      CA are inactivated by a two-step process. In the first step, a neurohormonal
      inhibition occurs by day 1 after ecdysis, resulting in a decrease in the ability
      of the glands to respond to allatotropin. The inhibitory hormone appears to be
      secreted by the medial neurosecretory cells in the brain and remains in the
      hemolymph only for a short period of <2 days. The second step of inactivation
      occurs by day 3; it is neurally mediated and essentially terminates juvenile
      hormone secretion. Neither the neurohormonal nor the neural inhibition is
      reversible under the conditions used in our larval assays. The timing of the two
      stages of inhibition coincides with the two periods of reduction in hemolymph
      juvenile hormone titer; this suggests that the regulation of corpus allatum
      activity plays an important role in reducing the juvenile hormone titer during
      the last larval instar-a prerequisite for the transformation of the larva into
      the pupa.

PMID- 16592859
TI  - Juvenile hormone-binding protein from the cytosol of Drosophila Kc cells.
AB  - Insect cells of an established line, Drosophila Kc cells, take up and metabolize
      juvenile hormone (JH). The cytoplasm of these cells contains a protein that binds
      JH with specificity, saturability, and high affinity (K(d) = 1.56 x 10(-8) M).
      The kinetics for the specific binding and dissociation of JH I were independently
      measured, and the rate constants were found to be k(a) = 1.3 x 10(6) M(-1) min(
      1), k(d) = 1.3 x 10(-2) min(-1), respectively. All three juvenile hormones bind
      to the protein with comparable affinities; the corresponding acid or diol
      metabolites of JH I are not bound. About 2500 hormone-binding protein molecules
      are present per cell. The protein has a molecular weight of 80,000 as estimated
      by gel permeation chromatography and by sucrose gradient sedimentation. The
      properties of this protein suggest that it functions as a cytoplasmic receptor
      for juvenile hormone.

PMID- 16592860
TI  - Energy transfer between photosystem II units in a connected package model of the
      photochemical apparatus of photosynthesis.
AB  - A model of the photochemical apparatus of photosynthesis, presented previously in
      a tripartite format, is used in a bipartite format to analyze energy transfer
      between photosystem II units. The model is used to develop analytical expressions
      for the photochemical properties of chloroplasts that include a term for the
      probability for energy transfer between photosystem II units. In particular, a
      normalized plot of the fluorescence of variable yield as a function of the
      closure of photosystem II reaction centers permits the evaluation of the energy
      transfer parameter. Data from a study by Melis [Melis, A. (1978) FEBS Lett. 95,
      202-206] are used to estimate that the probability for energy transfer between
      photosystem II units in the alpha component of photosystem II was approximately
      0.57 when the photosystem II reaction centers were all open and 0.83 when the
      centers were closed. This connected package model appears to provide a better
      description of the system than the matrix model that was used previously.

PMID- 16592861
TI  - Stoichiometry of system I and system II reaction centers and of plastoquinone in
      different photosynthetic membranes.
AB  - The concentrations of photochemical centers and of plastoquinone were measured in
      several kinds of photosynthetic membranes by optical difference spectroscopy.
      Photosystem I reaction centers were measured from the light-induced absorbance
      change at 700 nm (oxidation of the primary electron donor, P700). Photosystem II
      reaction centers were estimated from the light-induced absorbance change at 325
      nm (reduction of the primary electron acceptor, Q). Spinach chloroplasts and
      membrane fractions obtained by French press treatment, mature and developing pea
      chloroplasts, and blue-green algal membranes were investigated. No loss of
      primary photochemical activity occurred during fractionation of the chloroplasts.
      The results indicated a large variability in the ratio of system II to system I
      reaction centers (from 0.43 to 3.3) in different photosynthetic membranes. Oxygen
      evolving plants may change the ratio of their photosystems in response to
      environmental light conditions. The amount of photoreducible plastoquinone was
      also measured at 263 nm. In spinach chloroplasts, seven to eight plastoquinone
      molecules were found per reaction center of system II. Most of the plastoquinone
      pool was associated with the grana. However, the ratio of chemically determined
      plastoquinone to chlorophyll was similar in the grana and stroma thylakoids.

PMID- 16592862
TI  - Cytokinin inhibition of respiration in mitochondria from six plant species.
AB  - The influence of 6-benzylaminopurine (BAP) on the respiration by mitochondria
      from bush bean (Phaseolus vulgaris L.), mung bean (P. aureus Roxburgh), soybean
      [Glycine max (L.) Merrill], maize (Zea mays L.), pea (Pisum sativum L.), and
      wheat (Triticum aestivum L.) was examined. BAP, a synthetic cytokinin,
      consistently inhibited oxygen uptake by mitochondria from all species when malate
      was used as the substrate. The decrease in respiration was especially evident in
      the presence of ADP or an uncoupler of oxidative phosphorylation. 6
      Isopentenylaminopurine and 6-furfurylaminopurine also inhibited malate oxidation,
      but zeatin and adenine did not. In certain instances, BAP reduced succinate and
      NADH oxidation. With succinate as the substrate and with antimycin A present,
      inhibition by BAP paralleled that caused by salicylhydroxamic acid, an inhibitor
      of alternative respiration. A suggested scheme features a cytokinin-inhibited
      point located between NADH dehydrogenase and cytochrome b of the electron
      transport system. Electrons from the NADH generated by malate oxidation are
      assumed to flow through this point, with electrons from externally supplied or
      cytosolic NADH and succinate doing so only under certain conditions such as when
      alternative respiration is occurring. Cytokinin effects on respiration and
      perhaps on other phenomena may be mediated by this mechanism.

PMID- 16592863
TI  - Mammalian epidermal growth factor promotes plant growth.
AB  - Application of mouse submaxillary gland epidermal growth factor to young sorghum
      seedlings at low concentrations ( approximately 0.4-4 muM) increased shoot growth
      significantly over 3- and 6-day periods. The effects were dose dependent.

PMID- 16592864
TI  - Evolution of recombination in a constant environment.
AB  - The theory of evolution at a selectively neutral locus that controls the
      recombination between two major loci that are under selection is studied. If the
      major loci are at a stable equilibrium in linkage disequilibrium under selection
      and recombination, then a mutation at the modifier locus will increase in
      frequency when rare if and only if it decreases the recombination fraction. If
      the major loci are in disequilibrium at a balance between selection against
      deleterious alleles and mutation towards them, then two new phenomena are
      observed. First, a recombination increasing mutation will succeed if the
      disequilibrium is negative and the modifier is sufficiently tightly linked to the
      major loci. Second, depending on the strength of selection, even if the
      disequilibrium is negative, recombination reduction may occur for looser linkage
      between the major and modifier loci.

PMID- 16592865
TI  - Diffusion model for genotype-dependent migration.
AB  - A diffusion model for the joint action of genotype-dependent migration and
      genotype-independent population regulation is derived and investigated. The
      diploid, monoecious population occupies a finite chain of equally spaced
      colonies; generations are discrete and nonoverlapping; mating is random in each
      colony. A boundary-value problem is deduced for the gene frequencies at a
      multiallelic locus in the absence of mutation, selection, and random drift. This
      problem is studied for two alleles and constant and uniform population density
      and drift and diffusion coefficients. All equilibria are shown to be monotone,
      and explicit conditions for a protected polymorphism are established. Two
      examples of asymptotically stable clines are presented. It is demonstrated that
      genotype dependence of the mean displacements is necessary to produce or maintain
      spatial differentiation of gene frequencies.

PMID- 16592866
TI  - Duplicated cytosolic malate dehydrogenase genes in Zea mays.
AB  - Six inbred lines of Zea mays expressing different soluble (cytosolic) malate
      dehydrogenase (sMDH) zymogram phenotypes were analyzed genetically. sMDH was
      found to be coded for by unlinked duplicated loci in four of these inbred lines.
      The remaining two lines were found not to possess these duplicated loci.
      Furthermore, the duplicated loci, sMdh1 and sMdh2, have been found to be located
      on different chromosomes: sMdh1 on chromosome 1L linked to Amp1, and sMdh2 on
      chromosome 5S linked to Cat1 and Amp3. The importance of finding sMDH encoded by
      duplicated loci is discussed in relation to the role of chromosomal
      rearrangements, the relationship between the cytoplasmic and mitochondrial
      enzymes, and the evolution of Z. mays.

PMID- 16592867
TI  - Backlund transformations and nonlinear differential difference equations.
AB  - It is shown that any Backlund transformation of a nonlinear differential equation
      integrable by the multichannel Schrodinger eigenvalue problem can be written in
      the form V(x) = U'V - VU. This allows us to interpret the Backlund transformation
      formally as a nonlinear differential difference equation for which we can
      immediately construct the soliton solutions.

PMID- 16592869
TI  - A theoretical study of resonance Raman scattering from molecules: High pressure
      effect.
AB  - The main purpose of this paper has been to study the high pressure effect on the
      resonance Raman scattering (RRS) of molecules in a dense medium. In deriving the
      RRS cross section under high pressure, a different approach from that presented
      in the previous papers has been used, and the resulting expression for the RRS
      cross section can be used to treat both pressure and temperature effects.

PMID- 16592868
TI  - Coordination environment and fluoride binding of type 2 copper in the blue copper
      protein ascorbate oxidase.
AB  - The coordination environment of the type 2 (nonblue) copper in native ascorbate
      oxidase (L-ascorbate:oxygen oxidoreductase, EC 1.10.3.3) and of a derivative of
      the enzyme having the type 1 (blue) copper reversibly bleached has been examined
      by electron paramagnetic resonance (EPR) spectroscopy. In the g[unk] region of
      the spectrum of bleached ascorbate oxidase, a seven-line superhyperfine pattern
      is seen that is attributed to the presence of three nitrogen-donor ligands to a
      type 2 copper having tetragonal geometry. The superhyperfine splitting patterns
      in the g parallel region of the EPR spectra of native and bleached ascorbate
      oxidase show that as many as two fluorides may bind to type 2 copper. Because
      fluoride inhibits the enzyme competitively with respect to ascorbic acid, it is
      proposed that the type 2 copper is part of the ascorbate binding site.

PMID- 16592870
TI  - C and Hg nuclear magnetic resonance spectroscopic study of alkenemercurinium
      ions: Effect of methyl substituents on Hg chemical shifts.
AB  - The long-lived ethylene, cyclohexene, and norbornenemercurinium ions prepared in
      superacidic, low-nucleophilic media have been studied by (13)C and (199)Hg NMR
      spectroscopy. The norbornenemercurinium ion shows temperature-dependent (13)C and
      (199)Hg NMR spectra, consistent with equilibration via rapid hydride and Wagner
      Meerwin shifts. The (199)Hg NMR shifts of a series of alkylmercury bromides were
      also obtained in order to elucidate the effect of methyl substituents on (199)Hg
      NMR chemical shifts.

PMID- 16592871
TI  - Relationship between transfer activity coefficients, gamma, of cryptate 2.2.2
      complexes and their stability constant in various solvents.
AB  - Between dipolar aprotic solvents S(1) and S(2), the transfer activity
      coefficients, (S(1) )gamma(S(2) ), of complexed sodium, potassium, thallium(I),
      and silver ions with cryptand 2.2.2 have been found to be equal to that of the
      cryptand. With reference to methanol (S(1)), this equality does not hold, the
      cryptates being more or less solvated by hydrogen bonding in this solvent. In
      water as a solvent, the cryptates are on a considerably higher level of free
      energy than in the organic solvents. This is attributed to hydrophobic hydration
      of the cryptates.

PMID- 16592872
TI  - Meridional heat flux of the North Atlantic Ocean.
AB  - Using self-consistent geostrophic general circulation estimates for the North
      Atlantic Ocean as determined by an inverse method, I calculate the geostrophic
      and total meridional heat flux. The result is to a large extent dictated by the
      assumption of a fixed volume flux through the Florida Straits. There is no
      fundamental discrepancy between oceanic heat fluxes deduced from atmospheric
      residuals and those estimated directly in the ocean, including the estimates made
      here, simply because the error bars on all calculations are very large.

PMID- 16592873
TI  - A remark on the Conway-Norton conjecture about the "Monster" simple group.
AB  - By the method of second quantization we construct an infinite-dimensional graded
      module for the centralizer of an involution of the Fischer-Griess "Monster"
      simple group F(1) so that the Thompson series are those conjectured by Conway and
      Norton. As a consequence we obtain some identities and congruences relating
      modular functions j and eta. We are hopeful that this representation can be
      extended to the whole group F(1), proving all the conjectures by Conway and
      Norton in their recent paper [Conway, J. H. & Norton, S. P. (1979) Bull. London
      Math. Soc. 11, 308-339].

PMID- 16592874
TI  - Spectral theory for domains in R of finite measure.
AB  - Let Omega be a measurable subset of R(n) of finite positive Lebesgue measures.
      The following two problems are considered: (i) Find commuting self-adjoint
      extensions of the minimal operators -i( partial differential)/ partial
      differentialx(k), k = 1,..., n (Omega open). (ii) Find a set Lambda subset R(n)
      such that the functions e(lambda) = exp(ilambda(1)x(1) +... + ilambda(n)x(n)) for
      lambda in Lambda form an orthonormal basis for L(2)(Omega). The problems are
      known to be equivalent under mild regularity conditions on Omega, and existence
      holds in two cases: (i) there is a connected open set Omega' such that the
      symmetric difference OmegaDeltaOmega' is a null set and Omega' is a fundamental
      domain for a discrete total subgroup; and (ii)Omega = [unk](ainR) (a + [unk]),
      disjoint union neglecting null sets, in which [unk] is a fundamental domain and R
      is a "set of representors" for a finite group of translations. Case i is
      equivalent to a function theoretic condition of Forelli, and case ii is
      established when the existence of a discrete covariance group is assumed.
      Generalizations of the geometric results i and ii for spectral sets in arbitrary
      Lie groups are indicated.

PMID- 16592875
TI  - Fixed points of periodic maps.
AB  - Let f be a periodic differentiable map from a sphere to itself. A well-known
      conjecture of Smith asserts that in many cases (e.g., when the fixed points are
      isolated) the derivatives of f at its fixed points, regarded as Jacobian
      matrices, are linearly similar. Here we give counterexamples to this conjecture.
      The results show that, in many cases, these Jacobian matrices are only
      nonlinearly similar. This uses our recent discovery of orthogonal matrices which
      are nonlinearly similar without being linearly similar. Some results on general
      smooth actions of finite groups on differentiable manifolds are presented; the
      topological equivalence of their tangential representations at the fixed points
      is studied.

PMID- 16592877
TI  - Molecular cloning and characterization of potato spindle tuber viroid cDNA
      sequences.
AB  - Double-stranded cDNA has been synthesized from a polyadenylylated potato spindle
      tuber viroid (PSTV) template and inserted in the Pst I endonuclease site of
      plasmid pBR322 by using the oligo(dC).oligo(dG)-tailing procedure. Tetracycline
      resistant ampicillin-sensitive transformants contained sequences complementary to
      PSTV [(32)P]cDNA, and one recombinant clone (pDC-29) contains a 460-base-pair
      insert. This cloned double-stranded PSTV cDNA contains the cleavage sites for six
      restriction endonucleases predicted by the published primary sequence of PSTV as
      well as one additional site each for Ava I, Hae III, Hpa II, and Sma I. The
      additional Ava I, Hpa II, and Sma I sites are explained by the presence of a
      second C-C-C-G-G-G sequence in the cloned double-stranded cDNA. The largest
      fragment released by Hae III digestion contains approximately 360 base pairs.
      These results suggest that we have cloned almost the entire sequence of PSTV, but
      the sequence cloned differs slightly from that published. Hybridization probes
      derived from pDC-29 insert have allowed detection and preliminary
      characterization of RNA molecules having the same size as PSTV but the opposite
      polarity. This RNA is present during PSTV replication in infected tomato cells.

PMID- 16592876
TI  - Anchorage-independent muscle cell differentiation.
AB  - Cells from embryonic chicken muscle were cultivated in serum-free medium. After
      two days, the suspended cells (almost all of which were nondividing myoblasts)
      were subcultured in serum-containing medium, either in gelatincoated tissue
      culture dishes (to promote reattachment) or in bacteriological dishes (to prevent
      reattachment). The extent of fusion was high in both suspended and reattached
      cultures. Newly synthesized proteins from day-5 cultures were resolved by two
      dimensional electrophoresis and detected by autoradiography. Not only were the
      same protein species synthesized, but also the relative intensities of the spots
      corresponding to known muscle-specific proteins as well as the patterns of the
      many unidentified spots were similar. Synthesis of creatine kinase subunits B and
      M at different times was determined. In both suspended and reattached cells there
      was, as expected for differentiating myogenic cells, a marked increase by day 5
      in the ratio of M to B subunits synthesized. Immunofluorescent staining with
      antibodies against an M-line protein with M(r) 165,000 revealed myofibrils
      partially wound about the nuclei of suspended cells; these became strung out in
      the axis of the cell as reattached cells elongated. The synthesis of muscle
      proteins, their assembly into myofilaments, and formation of well-organized
      myofibrils is evidently not anchorage dependent. However, proper alignment of
      parallel arrays of myofibrils in register does appear to require cell attachment
      to substrate.

PMID- 16592878
TI  - Competitive intransitivity and size-frequency distributions of interacting
      populations.
AB  - The competitive ranking of three marine sessile organisms was determined from
      overgrowth observations and found to be intrasitive. Overgrowth results were
      dependent upon relative vertical relief which, in turn, was related to colony
      area. Discriminant function analysis demonstrates that competitive rankings can
      be largely predicted on the basis of knowledge of the size-frequency distribution
      of interacting populations. Because size increases with age for these species,
      size-dependent competition implies age-dependent competition. The role of age
      structure in determining the results of inter-specific interactions has been
      curiously neglected, particularly as it relates to competitive ability, yet the
      age dependence of competitive ability suggests (i) the occurrence of
      intransitivity in purely exploitative systems, (ii) a mechanism for frequency
      dependent behavior, (iii) the production of limit cycles, and (iv) the
      possibility of size refugia.

PMID- 16592879
TI  - Genetic regulation of the catalase developmental program in maize scutellum:
      Identification of a temporal regulatory gene.
AB  - Genetic and biochemical analyses suggest that the developmental program of
      catalase (H(2)O(2):H(2)O(2) oxidoreductase, EC 1.11.1.6) activity in maize
      scutella is controlled by a temporal regulatory gene (Car1) that is distinct from
      the structural genes thus far identified. Recombination data show that Car1 is
      located about 37 map units from the Cat2 structural gene on the chromosome 1S.
      Turnover studies indicate that Car1 may act by regulating the rate of catalase
      synthesis.

PMID- 16592880
TI  - A theory of distortion of the reaction zone.
AB  - A cylindrical detonating explosive behaves like a non-Newtonian viscous fluid
      emerging from a cylindrical pipe. The expression for non-Newtonian viscous flow
      has been applied to detonating explosives. The resultant fit to emerging flame
      fronts from detonation is excellent for a wide variety of detonating explosives
      both for transients (at various times) and for steady state. The quantities
      k'(lambda/lambda(1))(2/B) and 1/B and the rate constant k' increase abruptly at a
      time supporting a change in mechanism from deflagration to detonation in the
      transient during initiation. All of these parameters are temperature sensitive,
      indicating an abrupt temperature increase as a condition or indicator in the
      deflagration-to-detonation transition. Furthermore, a straight line results when
      log particle velocity u is plotted against log radial distance r, indicating
      that, for the explosives studied, the hyperbolic cosine wave front can be
      replaced by a parabolic wave front within the accuracy of the available
      experimental data.

PMID- 16592881
TI  - Microwave spectrum and molecular structure of the carbon monoxide-hydrogen
      bromide molecular complex.
AB  - Rotational spectra have been assigned for five isotopic species of the OC...HBr
      hydrogen-bonded molecular complex by using pulsed microwave Fourier transform
      spectroscopy in a Fabry-Perot cavity and a pulsed supersonic nozzle as the
      molecular source. The rotational constants, centrifugal distortion constants, Br
      nuclear-quadrupole-coupling constants, and Br spin-rotation constants were
      determined and from them, the vibrationally averaged structure of OCHBr was
      derived. This structure is consistent with a linear geometry at equilibrium and
      an atomic arrangement as written above. The intermolecular potential binding CO
      to HBr is discussed.

PMID- 16592882
TI  - Hypothetical strain-free oligoradicals.
AB  - Several new classes of oligoradicals free of angle strain are suggested and
      examined by means of molecular orbital calculations. The collapse products of
      these hypothetical radicals are highly strained molecules. Various electronic
      strategies for the stabilization of these oligoradicals have been explored.

PMID- 16592883
TI  - Photophysical properties of zinc and magnesium tris(pyrochlorophyllide a) 1,1,1
      tris(hydroxymethyl)ethane triesters.
AB  - The zinc and magnesium tris(pyrochlorophyllide a) 1,1,1-tris(hydroxymethyl)ethane
      triesters have properties that are very similar to those exhibited by pairs of
      pyrochlorophyll a or chlorophyll a linked by ethylene glycol through their
      propionic acid side chains. In the open configuration, the fluorescence lifetimes
      and emission spectra of the triesters resemble those of chlorophyll a monomers.
      However, the triesters have a mechanism for energy dissipation not present in
      monomeric chlorophyll a, which prevents the build-up of significant
      concentrations of molecules in S(1) states. Optical pumping of these compounds in
      their folded configuration results in the formation of high concentrations of
      molecules in S(1) states and in laser light emission, which originates from the
      two folded macrocycles. The optical data indicate that efficient energy transfer
      occurs from the open to the folded configurations.

PMID- 16592884
TI  - Influence of intramolecular hydrogen bonding on the electronic structure of
      oxymorphone.
AB  - Approximate ab initio molecular orbital methods are used to examine the
      structural and electronic properties of oxymorphone. The most stable conformation
      of the molecule is found to include an intramolecular hydrogen bond between the C
      14 hydroxyl group and the nitrogen atom in agreement with available experimental
      data. The total molecular electron density is transformed to a set of localized
      molecular orbitals, one of which corresponds to the lone electron pair on
      nitrogen. The hydrogen bond is shown to produce substantial bending and
      stretching of the lone pair when compared to its shape when such hydrogen bonding
      is precluded.

PMID- 16592885
TI  - Theoretical prediction of the vibrational spectra of group IB trimers.
AB  - The molecular structures of the group IB trimers, Cu(3), Ag(3), and Au(3), have
      been determined by using the semi-empirical diatomics-in-molecules theory. The
      trimers are found to have C(2v) symmetry with bond angles between 65 degrees and
      80 degrees . The trimers are bound with respect to dissociation to the asymptotic
      limit of an atom plus a diatom. The binding energies per atom for Cu(3), Ag(3),
      and Au(3) are 1.08, 0.75, and 1.16 eV, respectively. The vibrational frequencies
      of the trimers have been determined for comparison with experimental results. The
      vibrational frequencies are characterized by low values for the bending and
      asymmetric stretch modes. The frequency of the symmetric stretch of the trimer is
      higher than the stretching frequency of the corresponding diatomic. A detailed
      comparison of the theoretical results with the previously measured Raman spectra
      of matrix isolated Ag(3) is presented.

PMID- 16592886
TI  - Characters of irreducible Harish-Chandra modules and Goldie ranks of their
      annihilators.
AB  - Assume that G(C) is a simply connected complex semi-simple Lie group with Lie
      algebra [unk]. Let G subset G(C) be a real form, H subset G be a maximally split
      Cartan subgroup with Lie algebra [unk](0), [unk] = [unk](0) [unk] C, and P
      subset, dbl equals [unk](*) be the weight lattice. If X is an irreducible Harish
      Chandra module with infinitesimal character lambda in [unk](*), one can associate
      to X a family {theta(mu): mu in lambda + P} of Z-linear combinations of
      distribution characters of G, so that theta(lambda) = X. theta(mu) is irreducible
      when mu lies in C(lambda), a certain positive "Weyl" chamber containing lambda.
      In this case let Ann theta(mu) be its annihilator in U([unk]) and set p(mu) =
      Goldie rank of U([unk])/ Ann theta(mu). Let d = Gelfand-Kirillov dimension of X.
      For most x in [unk](0) if exp tx is regular for small t > 0 then (i) c(mu) =
      lim(t-->0(+) )t(d) theta(mu) (exp tx) exists for all mu in lambda + P; (ii) c(mu)
      extends to a homogeneous Weyl group harmonic polynomial on [unk](*) of degree
      (1/2)(dim G - dim H) - d; (iii) up to a constant, c = the polynomial extending p
      to [unk](*). c is said to be the character polynomial of Ann X.

PMID- 16592887
TI  - Coding of correlated sources with prescribed distortion by separated encoders.
AB  - Let (X(n),Y(n)) = (X(1),Y(1)),...,(X(n),Y(n)) be n independent, identically
      distributed pairs of chance variables. Each of two separated encoders encodes a
      different sequence of (X(n),Y(n)) to within given respective distortions
      z(1),z(2). Call a region in the plane of the respective rates (R(1),R(2)) M
      convex if it is convex, closed, and, to every point (r(1),r(2)), contains all
      points such that each of their coordinates is larger than or equal to the
      corresponding coordinate of (r(1),r(2)). This paper determines the (M-convex)
      region of achievable rates by giving its boundary. For z(1) = z(2) = 0, the
      region specializes to that of Slepian and Wolf. For z(2) = infinity and R(2) =
      H(Y(i)), the minimum R(1) is that of Wyner and Ziv; for z(2) = infinity and
      general given R(2), the minimum R(1) is that of my generalization of the theorem
      of Wyner and Ziv.

PMID- 16592888
TI  - Artin relation for smooth representations.
AB  - Let G be a finite group. If G acts smoothly on a closed homotopy sphere S, we
      call S a smooth representation of G. The main result is: There is a function h(G)
      such that for every smooth representation S of G, dimension S(G) = h(G){dimension
      S(H)H proper subgroup of G} if and only if G has prime power order and G is not
      cyclic. In other words, only for a noncyclic p-group G is dimension S(G) a
      universal function of the dimensions of the fixed sets S(H) as H ranges over
      proper subgroups of G. This result is compared with an old theorem of Artin's
      dealing with dimensions of fixed sets of orthogonal representations of G.

PMID- 16592889
TI  - On the asymptotic eigenvalue distribution of a pseudo-differential operator.
AB  - A description of the number N(K) of eigenvalues less than K for a pseudo
      differential operator with positive symbol is given in terms of the number of
      unit cubes canonically imbedded in the subset of phase space where the symbol is
      less than CK. This gives back in particular the order of magnitude of N(K) for
      elliptic symbols.

PMID- 16592890
TI  - Soliton dynamics in polyacetylene.
AB  - The equations of motion of the coupled electron-phonon system are integrated in
      real time for the model of polyacetylene recently proposed. To illustrate the
      physical behavior of this nonlinear system we consider the time evolution
      starting from three physically relevant configurations: (i) end generated
      soliton, (ii) electron-hole pair generation of a charged soliton-antisoliton
      pair, and (iii) the dressing of an injected electron. The calculations show that
      the system relaxes within a time of order 10(-13) sec, converting excited
      electron-hole pairs into soliton-antisoliton pairs.

PMID- 16592891
TI  - Ambient air concentration of sulfur dioxide affects flight activity in bees.
AB  - Three long-term (16-29 days) low-level (0.14-0.28 ppm) sulfur dioxide fumigations
      showed that exposure to this gas has deleterious effects on male sweat bees
      (Lasioglossum zephrum). Although effects on mortality were equivocal, flight
      activity was definitely reduced. Because flight is necessary for successful
      mating behavior, the results suggest that sulfur dioxide air pollution could
      adversely affect this and doubtless other terrestrial insects.

PMID- 16592892
TI  - Regulation of Rhizobium nitrogen fixation by the unadenylylated glutamine
      synthetase I system.
AB  - Rhizobium sp. 32H1 glutamine auxotrophs have a complex phenotype: a highly
      adenylylated glutamine synthetase [GS; L-glutamate:ammonia ligase (ADP-forming),
      EC 6.3.1.2] I and an undetectable GS II (GS II(-)). They are defective in the
      adenylylation cascade system for GS I. Prototrophic revertants are of two
      classes: those (3204 type) which retain the adenylylated GS I phenotype but
      become GS II(+), and those (3205 type) which acquire a constitutive
      unadenylylated GS I but remain GS II(-). Like the parent auxotroph, 3204 remains
      incapable of nitrogen fixation both in culture and in root nodules of
      Macroptileum atropurpureum. In contrast, 3205 is nitrogenase constitutive. This
      implies that GS I or associated adenylylation proteins are involved in the
      control of Rhizobium 32H1 nif gene expression and that GS II is not so involved.
      Normally, rhizobia fix atmospheric N(2) only during symbiosis and, in so doing,
      only transiently synthesize nitrogenase. Moreover, whereas wild-type strains
      export ammonium, constitutive strains can assimilate ammonium produced by
      nitrogenase. This phenotype allows direct selection of nitrogen fixation
      defective mutants in Rhizobium.

PMID- 16592893
TI  - Magnetic field-induced increase in chlorophyll a delayed fluorescence of
      photosystem II: A 100- to 200-ns component between 4.2 and 300 K.
AB  - At room temperature the delayed fluorescence (luminescence) of spinach
      chloroplasts, in which the acceptor Q is prereduced, consists of a component with
      a lifetime of 0.7 mus and a more rapid component, presumably with a lifetime of
      100-200 ns and about the same integrated intensity as the 0.7- mus component.
      Between 4.2 and 200 K only a 100- to 200-ns luminescence component was found,
      with an integrated intensity appreciably larger than that at room temperature. At
      77 K the 150-ns component approached 63% of saturation at roughly the same energy
      as the variable fluorescence of photosystem II at room temperature. At 77 K the
      emission spectra of prompt fluorescence but not that of the 150-ns luminescence
      had a preponderant additional band at about 735 nm. The 150-ns emission also
      occurred in the photosystem I-lacking mutant FL5 of Chlamydomonas. These
      experiments indicate that the 150-ns component originates from photosystem II. At
      room temperature a magnetic field of 0.22 T stimulated the 0.7-mus delayed
      fluorescence by about 10%. At 77 K the field-induced increase of the 150-ns
      component amounted to 40-50%, being responsible for the observed approximately 2%
      increase of the total emission; the magnetic field increased the lifetime about
      20%. In order to explain these phenomena a scheme for photosystem II is presented
      with an intermediary acceptor W between Q and the primary donor chlorophyll P
      680; recombination of P-680(+) and W(-) causes the fast luminescence. The
      magnetic field effect on this emission is discussed in terms of the radical pair
      mechanism.

PMID- 16592894
TI  - Nigericin-stimulated ATPase activity in microsomal vesicles of tobacco callus.
AB  - The effect of ionophores on K(+)-stimulated adenosinetriphosphatase (ATPase; ATP
      phosphohydrolase, EC 3.6.1.3) activity of microsomal vesicles from tobacco callus
      was investigated. A nigericin-stimulated K(+)-ATPase activity was enriched in a
      purified microsomal fraction, which was obtained from the interphase of a dextran
      density gradient between 1.03 and 1.06 g/ml. The purified microsomal fraction was
      free of mitochondrial membranes and was composed partly of tightly sealed
      vesicles as indicated by the low K(+) permeability coefficient. The K(+)
      dependent ATPase of this fraction was stimulated slightly by either carbonyl
      cyanide m-chlorophenylhydrazone (CCCP) (29%) or valinomycin (31%) alone; this
      ATPase was significantly stimulated by a combination of CCCP and valinomycin
      (73%) or by nigericin alone (80%). The K(+)-ATPase activity was stimulated by
      nigericin at pH 6.5 but not at pH 8.5. At pH 6.5, the K(+)-ATPase was inhibited
      by N,N'-dicyclohexylcarbodiimide but not by oligomycin. Nigericin stimulated the
      ATPase activity in the absence of initial KCl or pH gradients across the vesicle
      membrane. These results suggest that nigericin stimulates the ATPase activity by
      dissipating the H(+) or K(+) gradient or both, and support the hypothesis that
      the K(+)-ATPase mediates a H(+)/K(+) transport.

PMID- 16592895
TI  - Regulation of the hexosamine biosynthetic pathway in the water mold
      Blastocladiella emersonii: Sensitivity to endproduct inhibition is dependent upon
      the life cycle phase.
AB  - Chitin, a homopolymer of N-acetylglucosamine (GlcNAc), is the major
      macromolecular constituent of Blastocladiella emersonii cell walls. Zoospores do
      not possess a wall nor do they contain sufficient total hexosamine to account for
      the chitin content of the wall abruptly formed during germination. UDPGlcNAc,
      both the endproduct of hexosamine biosynthesis and the substrate for chitin
      synthesis, is present in zoospores in sufficient concentration to inhibit the
      first hexosamine pathway-specific enzyme activity. Net chitin accumulates in
      register with dry weight during exponential growth, but does not accumulate
      appreciably during the succeeding sporulation phase. Predicted relationships
      among net rates of chitin synthesis, UDPGlcNAc concentrations, and UDP plus UTP
      concentrations throughout the life cycle are explored, as are the assumptions
      upon which the predictions were based. We find that the sensitivity of the first
      hexosamine pathway-specific enzyme to endproduct inhibition is not constant
      throughout the life cycle; sensitivity is very high in the zoospore phase,
      decreases dramatically during germination, remains very low through the growth
      phase, and increases gradually to the zoospore level during sporulation. The
      organism appears to have evolved endproduct regulation in this case as an
      adaptation to "hard-times" phases of the life cycle-i.e., as a safeguard against
      overproduction of end product (UDPGlcNAc) when its utilization in cell wall
      (specifically chitin) synthesis is curtailed. Conversely, the organism
      effectively discards this mode of regulation during "good times," when the
      demands for end product are evidently greater than endproduct inhibition would
      otherwise permit.

PMID- 16592896
TI  - Transformation in Agmenellum quadruplicatum.
AB  - A DNA-mediated transformation system for the blue-green alga Agmenellum
      quadruplicatum, strain PR-6, is described and characterized for DNA concentration
      dependence, dependence on time of exposure to DNA, phenotypic expression,
      sensitivity to various enzymes, and competence. The stability of the
      transformants has been investigated, and genetic backcross and selfing
      experiments have been performed. This system fulfills all of the criteria
      established for the well-characterized transformation systems in heterotrophic
      bacteria and demonstrates significant similarities to at least one of these
      systems for all characteristics examined. The efficiency of transformation is
      high. This system fills a need for a well-characterized genetic system in an
      oxygen-evolving photoautotroph. We have used it to transform a strain with a
      mutational lesion in assimilatory nitrogen metabolism to a wild-type genotype.

PMID- 16592898
TI  - Gene-culture translation in the avoidance of sibling incest.
AB  - A preliminary analysis is made of the relation between the epigenetic rules of
      brother-sister incest avoidance, which operate during individual development, and
      the frequency of occurrence of this form of incest among cultures.

PMID- 16592897
TI  - Inheritance of chloroplast DNA in Chlamydomonas reinhardtii.
AB  - Two symmetrically located deletions of approximately 100 base pairs each have
      been identified in chloroplast DNA of Chlamydomonas reinhardtii. Although present
      in a mutant strain that requires acetate for growth, both deletions have been
      shown to be distinct from the nonphotosynthetic phenotype of this strain. These
      physical markers in the chloroplast genome and maternally inherited genetic
      markers showed strict cotransmission in reciprocal crosses. Thus, our results are
      consistent with the location of the well-characterized maternally inherited
      genetic markers in chloroplast DNA of C. reinhardtii.

PMID- 16592899
TI  - Computers-Present and future: Introduction to the symposium.

PMID- 16592901
TI  - Computers-Small computers: Past, present, and future.

PMID- 16592900
TI  - Computers-Work in progress.

PMID- 16592902
TI  - Computers-The software situation.

PMID- 16592903
TI  - Computers-Non-numerical computation.

PMID- 16592904
TI  - Dedicated-site, interim storage of high-level nuclear waste as part of the
      management system.
AB  - Dedicated-site interim storage of high-level reprocessed nuclear waste and of
      spent fuel rods is proposed as a long-term integral part of the systems approach
      of the national nuclear waste isolation program. Separation of interim sites for
      retrievable storage from permanent-disposal repositories should enhance ensurance
      of the performance of the latter; maintenance of retrievability at separate sites
      also has many advantages in both safety and possible use of waste as resources.
      Interim storage sites probably will not be needed beyond about 100 years from
      now, so the institutional and technical considerations involved in their choice
      should be much less stringent than those for the selection of permanent sites.
      Development of interim sites must be concurrent with unabated effort to identify
      and to develop permanent repositories.

PMID- 16592905
TI  - Phase separation in mixtures of ionized iron in a hydrogen plasma.
AB  - The accuracy of the hypernetted chain theory for mixtures of iron nuclei and
      protons in a charge-neutralizing background is demonstrated by comparison with
      molecular dynamics calculations. Near critical conditions the Debye-Huckel
      approximation fails to converge, even with second-order concentration
      corrections. The critical conditions, determined by assuming a uniform electron
      gas background, have a critical temperature more than a factor of 2 lower than
      present estimates of interior solar conditions. Qualitative arguments are made
      that including the polarization of the electron gas background would not change
      this result significantly and thus phase separation of iron in the interior of
      the sun is unlikely.

PMID- 16592906
TI  - Statistical invalidation of the Hubble law.
AB  - An optimal nonparametric technique for elimination of the observation cutoff
      bias, on the assumption of a given theoretical cosmology, is applied to the
      redshift-magnitude and redshift-angular diameter relationships in objectively
      specified large galaxy samples. The estimates obtained on the assumptions of
      linear and square redshift-distance laws are uniformly and strongly favorable to
      the square law. The question of whether the relative inferiority of the linear
      law can scientifically be ascribed to ancillary extragalactic phenomena is
      addressed by nonparametric crosstesting of the alternative hypotheses. Each law
      is used to predict the results of a statistical analysis based on the alternative
      law by using the given data and computer simulations. The result is that the
      square law predicts with statistical exactitude the results of the analyses of
      the linear law; but the linear law predicts with near certainty that the fit of
      the square law will be much worse than is observed. In the absence of independent
      validation of a variety of ancillary hypotheses that have been adduced in
      connection with the linear law, it seems necessary to conclude that the Hubble
      law lacks an objective statistical foundation.

PMID- 16592907
TI  - Synthesis and characterization of a photosensitive interface for hydrogen
      generation: Chemically modified p-type semiconducting silicon photocathodes.
AB  - p-Si photocathodes functionalized first with an N,N'-dialkyl-4,4'-bipyridinium
      redox reagent, (PQ(2+/+-))(surf), and then with a Pt precursor, PtCl(6) (2-),
      give significant efficiency (up to 5%) for photoelectrochemical H(2) generation
      with 632.8-nm light. Naked p-Si photocathodes give nearly zero efficiency, owing
      to poor H(2) evolution kinetics that are improved by the (PQ(2+/+-))(surf)/Pt
      modification. The mechanism of H(2) evolution from p-Si/(PQ(2+/+-))(surf)/Pt is
      first photoexcitation of electrons to the conduction band of Si followed by
      (PQ(2+))(surf) --> (PQ(+-))(surf) reduction. The dispersion of Pt then catalyzes
      H(2)O reduction to give H(2) and regeneration of (PQ(2+))(surf). The overall
      energy conversion efficiency rivals the best direct optical to chemical
      conversion systems reported to date.

PMID- 16592908
TI  - Chemical potential, Teller's theorem, and the scaling of atomic and molecular
      energies.
AB  - FOR ATOMS AND HOMONUCLEAR DIATOMIC MOLECULES, IT IS ARGUED THAT THE ELECTRONIC
      ENERGIES HAVE THE FORMS [FORMULA: see text] and [Formula: see text] [Formula: see
      text], respectively,where Z is the atomic number, N is the number of electrons,
      and R is the internuclear distance. By using the Lieb-Simon theorem that the
      Thomas-Fermi theory is exact in the limit of large atomic number and the Teller
      theorem that molecules are not bound in the Thomas-Fermi theory, it is then
      shown, among other results, that the electron-electron repulsion energy for
      neutral systems has no term in Z(2) and that the nucleus-nucleus repulsion energy
      for neutral molecules is probably [unk](Z(5/3)). For neutral atoms, it is
      predicted and verified that the chemical potential (electronegativity) is
      [unk](Z(-1/3)) for large Z. Tetrahedral and octahedral molecules are briefly
      discussed.

PMID- 16592909
TI  - Mg NMR in DNA solutions: Dominance of site binding effects.
AB  - (25)Mg NMR spectroscopy is applied to a study of magnesium ion interactions with
      DNA, which is considered as a model for a linear polyelectrolyte. It is
      demonstrated that the magnesium ion spectrum is complicated by a non-Lorent-zian
      line shape and is dominated by the effects of chemical exchange with
      macromolecule binding sites. A distinction is made between specific-site
      interactions in which the magnesium ion loses a water molecule from the first
      coordination sphere on binding and those interactions, referred to as territorial
      binding, in which the ion maintains its first coordination sphere complement of
      solvent. The first type of site-binding interactions are shown to dominate the
      magnesium ion NMR spectrum, based on a consideration of the magnitudes of the
      observed (25)Mg relaxation rates compared with (23)Na relaxation rates, the clear
      contributions of chemical exchange-limited relaxation, and an ion displacement
      experiment employing sodium.

PMID- 16592910
TI  - Analytic construction of Hartree-Fock density matrices.
AB  - A method is presented for variational calculation of the energy and the spin
      densities derived from a single-determinant wavefunction. Sum and difference
      coordinates [unk]R = (1/2)([unk]r(1) + [unk]r(1)) and [unk]r = [unk]r(1) -
      [unk]r(1) are introduced, and the density matrix P([unk]r(1),[unk]r(1)) is
      expanded in partial waves in the new coordinate frame: [Formula: see text] The
      functions h(L)(epsilon,r) are bound or continuum hydrogenic functions with energy
      epsilon.It is shown that the spin densities depend on the s partial waves only,
      and a Euler equation for these partial waves is derived: [Formula: see text] in
      which U([unk]R) is the electrostatic potential, a(epsilon) = h(0)(epsilon,0), and
      mu is chosen to normalize the spin density to N electrons. Further, the
      electronic energy can be expressed in terms of the s partial waves and the
      constant mu in the above equations.The idempotent density matrix that ensues from
      a particular choice of functions {B(00)[unk](epsilon,[unk]R)} is generated by
      choosing partial density waves {B(LM)(epsilon,[unk]R), L > 0} so that tr[P(2)(1 -
      P)(2)] is minimized.

PMID- 16592911
TI  - A two-reservoir recycling model for mantle-crust evolution.
AB  - The exact solutions for the isotopic compositions and the concentrations of the
      two-reservoir model for mantle-crust evolution are given for arbitrary rates of
      crustal growth and of back flow to the mantle. The critical parameters are the
      chemical fractionation factors for crustal growth and refluxing and the
      integrated fractional mass-removal rates from the crust and the mantle. For the
      case where refluxing is proportional to crustal growth, all the solutions reduce
      to simple analytic expressions. The expression for the mean age of the mass of
      the crust with refluxing is given. If refluxing is significant, the model shows
      that highly incompatible elements have short residence times in the mantle. With
      plausible concentration values, material balance implies that the continents were
      derived from only a small fraction of the mantle.

PMID- 16592912
TI  - Spinor representations of affine Lie algebras.
AB  - Let [unk] be an infinite-dimensional Kac-Moody Lie algebra of one of the types
      D(l+1) ((2)), B(l) ((1)), or D(l) ((1)). These algebras are characterized by the
      property that an elimination of any endpoint of their Dynkin diagrams gives
      diagrams of types B(l) or D(l) of classical orthogonal Lie algebras. We construct
      two representations of a Lie algebra [unk], which we call spinor representations,
      following the analogy with the classical case. We obtain that every spinor
      representation is either irreducible or has two irreducible components. This
      provides us with an explicit construction of fundamental representations of
      [unk], two for the type D(l+1) ((2)), three for B(l) ((1)), and four for D(l)
      ((1)). We note the profound connection of our construction with quantum field
      theory-in particular, with fermion fields. Comparing the character formulas of
      our representations with another construction of the fundamental representations
      of Kac-Moody Lie algebras of types A(l) ((1)), D(l) ((1)), E(l) ((1)), we obtain
      classical Jacobi identities and addition formulas for elliptic theta-functions.

PMID- 16592913
TI  - Why is there no bulk specific heat anomaly at the superconducting transition
      temperature of BaPb(1-x) Bi(x) O(3)?
AB  - Caloric measurements have shown that there is no bulk specific heat anomaly at
      the superconducting transition temperature of BaPb(0.75)Bi(0.25)O(3).

PMID- 16592914
TI  - Sodium-dependent silicate transport in the apochlorotic marine diatom Nitzschia
      alba.
AB  - Silicate uptake by Nitzschia alba cells is higher in medium containing Na(+) than
      in media lacking Na(+) but containing K(+), Rb(+), NH(4) (+), Li(+), or
      choline(+). The initial rate is inhibited by monensin and gramicidin but not by
      valinomycin or nigericin and is less sensitive to inhibition by carbonyl cyanide
      m-chlorophenylhydrazone (CCCP). In isolated membrane vesicles, silicate is taken
      up when a Na(+) gradient is imposed across the membrane or is generated by
      cytoplasmic Na(+),K(+)-ATPase. H(+) or K(+) gradients in either direction do not
      stimulate uptake. Na(+)-gradient-dependent uptake is inhibited by monensin but
      not by CCCP, valinomycin, or vanadate, which inhibits the cytoplasmic Na(+),K(+)
      ATPase. Uptake increases if an internally negative potential is imposed across
      the membrane. The vesicular uptake shows saturation kinetics with a K(m) of 62
      muM and a V(max) of 4.1 nmol/mg of protein per min. In intact cells, the initial
      rate of silicate uptake increases with pH up to 9.5. Thus, in N. alba, silicate
      is symported with Na(+), and the transport system is driven by the Na(+) gradient
      that is generated and maintained across the membrane by the activity of
      Na(+),K(+)-ATPase.

PMID- 16592915
TI  - Recombination between higher plant DNA and the Ti plasmid of Agrobacterium
      tumefaciens.
AB  - The Ti plasmid sequences (T-DNA) from the octopine-producing crown gall tumor
      A6S/2 were isolated by molecular cloning, using the bacteriophage lambda vector
      Charon 4A. Analysis of the cloned DNA segments indicates that the Ti plasmid
      sequences are covalently joined to plant nuclear DNA. These data demonstrate that
      genetic recombination between a eukaryote and a prokaryote can occur as a natural
      phenomenon.

PMID- 16592916
TI  - Nucleotide sequence of a cyanobacterial nifH gene coding for nitrogenase
      reductase.
AB  - The nucleotide sequence of nifH, the structural gene for nitrogenase reductase
      (component II or Fe protein of nitrogenase) from the cyanobacterium Anabaena 7120
      has been determined. Also reported are 194 bases of the 5'-flanking sequence and
      170 bases of the 3'-flanking sequence. The predicted amino acid sequence was
      compared with that determined for the complete nitrogenase reductase of
      Clostridium pasteurianum and the cysteine-containing peptides of the protein from
      Azotobacter vinelandii. Amino acid sequences around five cysteines, located in
      the NH(2)-terminal two-thirds of the protein, are highly conserved in all three
      species. Codon usage in the first gene from a cyanobacterium to be sequenced
      shows striking asymmetries for eight amino acids.

PMID- 16592917
TI  - Regulatory coupling of nitrate and sulfate assimilation pathways in cultured
      tobacco cells.
AB  - When cultured tobacco cells are provided growth-limiting concentrations of sulfur
      as sulfate, the rate of development of nitrate reductase (NADH:nitrate
      oxidoreductase, EC 1.6.6.1) is proportional to the initial sulfate concentration.
      When the cells are provided growth-limiting concentrations of nitrogen as
      nitrate, the rate of derepression of ATP sulfurylase (ATP:sulfate
      adenylyltransferase, EC 2.7.7.4) is proportional to the initial nitrate
      concentration. These results are taken to be indicative of a reciprocal
      regulatory coupling between the nitrate and sulfate assimilation pathways.

PMID- 16592918
TI  - Cellulose biogenesis: Polymerization and crystallization are coupled processes in
      Acetobacter xylinum.
AB  - Calcofluor White ST, stilbene derivative used commerically as an optical
      brightener for cellulose, increased the rate of glucose polymerization into
      cellulose by resting cells of the gram-negative bacterium Acetobacter xylinum.
      This bacterium normally produces a ribbon of cellulose that is a composite of
      crystalline microfibrils. In concentrations above 0.1 mM, Calcofluor disrupts the
      assembly of crystalline cellulose I microfibrils and their integration into a
      composite ribbon by stoichiometric binding to glucose residues of newly
      polymerized glucan chains. Under these conditions, the rate of glucose
      polymerization increases up to 4 times the control rate, whereas oxygen uptake
      increases only 10-15%. These observed effects are readily reversible. If free
      Calcofluor is washed away or depleted below the threshold value by binding to
      cellulose as polymerization continues, ribbon production and the normal rate of
      polymerization resume. It is concluded that polymerization and crystallization
      are cell-directed, coupled processes and that the rate of crystallization
      determines the rate of polymerization. It is suggested that coupling must be
      maintained for biogenesis of crystalline cellulose I.

PMID- 16592919
TI  - Asynchronous replication of heterochromatin in maize.
AB  - Replication patterns of four classes of heterochromatin in the chromosomes of
      maize were analyzed. Centromeric heterochromatin, distal heterochromatin of the B
      chromosomes, and knob heterochromatin all have asynchronous late replication,
      knob heterochromatin being the last chromosomal DNA to complete replication.
      Nucleolus organizer heterochromatin replicates during the period of euchromatin
      DNA replication. The proportion of the S period involved in asynchronous late
      replication is directly dependent on the amount of heterochromatin in the
      nucleus. Both additional knob and B-chromosome heterochromatin participate in
      this effect. Each additional B chromosome produces an increment in the proportion
      of nuclei with asynchronous replication; in nuclei with 12 B chromosomes, the
      proportion of the S phase showing asynchronous late replication is more than 3
      times greater than that in nuclei without B chromosomes. The data are consistent
      with the hypothesis that delayed DNA replication of knob heterochromatin is
      responsible, in some genotypes, for the loss of chromosome segments and for B
      chromosome nondisjunction in the second pollen grain mitosis.

PMID- 16592920
TI  - Genetic variability and effective population size when local extinction and
      recolonization of subpopulations are frequent.
AB  - If a population (species) consists of n haploid lines (subpopulations) which
      reproduce asexually and each of which is subject to random extinction and
      subsequent replacement, it is shown that, at equilibrium in which mutational
      production of new alleles and their random extinction balance each other, the
      genetic diversity (1 minus the sum of squares of allelic frequencies) is given by
      2N(e)v/(1 + 2N(e)v), where [Formula: see text] in which N is the harmonic mean of
      the population size per line, n is the number of lines (assumed to be large),
      lambda is the rate of line extinction, and v is the mutation rate (assuming the
      infinite neutral allele model). In a diploid population (species) consisting of n
      colonies, if migration takes place between colonies at the rate m (the island
      model) in addition to extinction and recolonization of colonies, it is shown that
      effective population size is [Formula: see text] If the rate of colony extinction
      (lambda) is much larger than the migration rate of individuals, the effective
      population size is greatly reduced compared with the case in which no colony
      extinctions occur (in which case N(e) = nN). The stepping-stone type of
      recolonization scheme is also considered. Bearing of these results on the
      interpretation of the level of genetic variability at the enzyme level observed
      in natural populations is discussed from the standpoint of the neutral mutation
      random drift hypothesis.

PMID- 16592921
TI  - A cardioactive factor in human plasma with positive inotropic and positive
      chronotropic activities.
AB  - A cardioactive factor with a molecular weight of about 100,000 and that exhibits
      positive inotropic and positive chronotropic activity on isolated guinea pig
      atria has been found in human plasma. The positive inotropic activity is less
      stable than the positive chronotropic activity. The two activities move together
      in cation- and anion-exchange chromatography, gelfiltration chromatography, and
      polyethylene glycol precipitation. They may be associated with a single large
      polypeptide or with different subunits of a complex protein.

PMID- 16592922
TI  - Alternative male life histories in bluegill sunfish.
AB  - MALE BLUEGILL SUNFISH ARE SHOWN TO HAVE TWO ALTERNATIVE MATING STRATEGIES:
      cuckoldry or parental care. Cuckolder males first mature at age 2. They follow a
      developmental sequence of sneaking and then mimicking female behavior to
      deceptively gain access to spawnings. Males who become parentals (construct
      nests, attract females, provide brood care) delay maturation until age 7. The
      parental investment of these males is parasitized by the cuckolders. This system
      is an example of a truly parasitically dependent mating strategy in vertebrates.
      A natural selection model is developed to predict the equilibrium frequencies of
      the two male types. A preliminary test of the model provides qualitative
      agreement.

PMID- 16592923
TI  - Quantization of wave equations and hermitian structures in partial differential
      varieties.
AB  - Sufficiently close to 0, the solution variety of a nonlinear relativistic wave
      equation-e.g., of the form squarevarphi + m(2)varphi + gvarphi(p) = 0-admits a
      canonical Lorentz-invariant hermitian structure, uniquely determined by the
      consideration that the action of the differential scattering transformation in
      each tangent space be unitary. Similar results apply to linear time-dependent
      equations or to equations in a curved asymptotically flat space-time. A close
      relation of the Riemannian structure to the determination of vacuum expectation
      values is developed and illustrated by an explicit determination of a
      perturbative 2-point function for the case of interaction arising from curvature.
      The theory underlying these developments is in part a generalization of that of
      M. G. Krein and collaborators concerning stability of differential equations in
      Hilbert space and in part a precise relation between the unitarization of given
      symplectic linear actions and their full probabilistic quantization. The unique
      causal structure in the infinite symplectic group is instrumental in these
      developments.

PMID- 16592924
TI  - Gaseous isotope separation using solar wind phenomena.
AB  - A large evacuated drum-like chamber fitted with supersonic nozzles in the center,
      with the chamber and the nozzles corotating, can separate gaseous fluids
      according to their molecular weights. The principle of separation is essentially
      the same as that of the solar wind propagation, in which components of the plasma
      fluid are separated due to their difference in the time-of-flight. The process
      can inherently be very efficient, serving as a pump as well as a separator, and
      producing well over 10(5) separative work units (kg/year) for the
      hydrogen/deuterium mixture at high-velocity flows.

PMID- 16592925
TI  - Energy transfer from PO excited states to alkali metal atoms in the phosphorus
      chemiluminescence flame.
AB  - Phosphorus chemiluminescence under ambient conditions of a phosphorus oxidation
      flame is found to offer an efficient electronic energy transferring system to
      alkali metal atoms. The lowest resonance lines, (2)P(3 / 2),(1/2)-->(2)S((1/2)),
      of potassium and sodium are excited by energy transfer when an argon stream at 80
      degrees C carrying potassium or sodium atoms intersects a phosphorus vapor
      stream, either at the flame or in the postflame region. The lowest electronically
      excited metastable (4)II(i) state of PO or the (PO[unk]PO)(*) excimer is
      considered to be the probable energy donor. The (PO[unk]PO)(*) excimer results
      from the interaction of the (4)II(i) state of one PO molecule with the ground
      (2)II(r) state of another. Metastability of the donor state is strongly indicated
      by the observation of intense sensitized alkali atom fluorescence in the
      postflame region.

PMID- 16592926
TI  - Structural effects in solvolytic reactions; carbon-13 NMR studies of
      carbocations: Effect of increasing electron demand on the carbon-13 NMR shifts in
      substituted tert-cumyl and 1-aryl-1-cyclopentyl carbocations-correlation of the
      data by a new set of substituent constants, sigma.
AB  - The cationic carbon substituent chemical shifts (DeltadeltaC(+)) for nine
      representative meta-substituted tert-cumyl carbocations are correlated
      satisfactorily by the sigma(m) (+) substituent constants (slope rho+ = -18.18,
      correlation coefficient r = 0.990). However, the substituent chemical shifts
      (DeltadeltaC(+)) for the corresponding para derivatives are not correlated by the
      sigma(p) (+) substituent constants. The possibility of developing a set of
      substituent constants capable of correlating such (13)C NMR shifts was examined.
      The slope of the line defined by the meta substituents (rho+ = -18.18) was
      utilized to calculate sigma(C+) constants for both meta and para substituents.
      The utility of these constants was then tested by their ability to correlate the
      (13)C NMR shifts in the cations for a different system, the 1-aryl-1-cyclopentyl
      cations. Indeed, these sigma(C+) values correlate very well with the
      DeltadeltaC(+) values, yielding rho(C+) = -16.84, r = 0.999.

PMID- 16592927
TI  - Stereochemical consequences of dynamic gearing in substituted bis(9-triptycyl)
      methanes and related molecules.
AB  - Empirical force-field calculations show that bis(9-triptycyl)methane has a C(s)
      ground state and that the securely meshed triptycyl groups undergo nearly
      unhindered cogwheel rotation through a C(2) transition state, with an activation
      energy of approximately 1.0 kcal mol(-1). These features lead to note-worthy
      stereochemical attributes in appropriately substituted derivatives and analogs.
      Bis(9-triptycyl)carbinol has been prepared as an example of a compound that is
      chemically achiral, even though all conformations are chiral under the constraint
      of gear meshing. It is shown that, under the same constraint, ring substitution
      of either compound (or analogous systems) may lead to residual stereoisomerism. A
      permutational analysis of chemical isomers and isomerizations for every possible
      type of substitution pattern gives an enumeration of residual stereoisomers under
      the operation of various gearing and nongearing modes and provides information
      essential for a choice among mechanistic alternatives for a given isomer count.

PMID- 16592928
TI  - Intermolecular anti-parallel beta sheet: Comparison of predicted and observed
      conformations of gramicidin S.
AB  - A recently determined x-ray structure of the hydrated gramicidin S-urea complex
      is compared with a structure predicted by conformational energy minimization. It
      is shown that the two structures are in good general agreement, including the
      prediction of a hydrogen bond between the side-chain amino group of ornithine and
      the backbone carbonyl of phenylalanine. This agreement demonstrates the power of
      empirical potential energy methods in conformational analysis and illustrates one
      method for solution of the multiple-minimum problem for small peptides. It is
      noted that, in the crystal, gramicidin S is a dimer that forms an intermolecular
      antiparallel four-stranded beta sheet and that differences between the predicted
      and x-ray structures can be explained by this intermolecular interaction. The
      residual conformational asymmetry of the x-ray structure is shown to be due to
      the formation of the complex with urea.

PMID- 16592929
TI  - Relative sea levels from tide-gauge records.
AB  - Mean annual sea levels at 247 tide-gauge stations of the world exhibit a general
      rise of relative sea level of about 3 mm/year during the past 40 years. In
      contrast, general uplift of the land is typical of high northern latitudes, where
      unloading of the crust by melt of Pleistocene ice sheets is significant. Erratic
      movements are typical of belts having crustal overthrusting and active volcanism.
      Short-term (5- and 10-year) records reveal recent changes in rates, but such
      short time spans may be so influenced by climatic cycles that identification of
      new trends is difficult, especially with the existing poor distribution and
      reporting of tide-gauge data.

PMID- 16592930
TI  - Chemical composition of Earth, Venus, and Mercury.
AB  - Model compositions of Earth, Venus, and Mercury are calculated from the premise
      that planets and chondrites underwent four identical fractionation processes in
      the solar nebula. Because elements of similar properties stay together in these
      processes, five constraints suffice to define the composition of a planet: mass
      of the core, abundance of U, and the ratios K/U, Tl/U, and FeO/(FeO + MgO).
      Complete abundance tables, and normative mineralogies, are given for all three
      planets. Review of available data shows only a few gross trends for the inner
      planets: FeO decreases with heliocentric distance, whereas volatiles are depleted
      and refractories are enriched in the smaller planets.

PMID- 16592931
TI  - An atomic kinetic energy functional with full Weizsacker correction.
AB  - A functional is proposed for representing the electronic kinetic energy of the
      ground state of an N-electron atom or ion in terms of its electron density,
      [Formula: see text] Here T(w) is the Weizsacker quantity
      ((1/8))integral(nablarho.nablarho/rho)dtau and T(0) is the Thomas-Fermi quantity
      C(F) integral rho(5 / 3)dtau. From Hartree-Fock data on 55 neutral atoms, C =
      1.412 +/- 0.033; for 1200 atoms and ions, C = 1.332 +/- 0.053. The proposed
      functional gives the derivative deltaT/deltarho its most important correct
      properties. The term T(w) is shown to give the kinetic energy of the K shell,
      whereas the term (C/N((1/3)))T(0) gives an incorrect statistical estimate of that
      energy. An alternative correction -(C/N((1/3)))T gives even better results.

PMID- 16592932
TI  - Stationary convection in dilute solutions of He in superfluid He.
AB  - Two symmetric, convecting steady states have been observed in a novel cell of
      unity aspect ratio and studied over a range of temperature for two concentrations
      of (3)He in superfluid (4)He. An existing theory due to Parshin has been related
      to the conditions necessary for convection in this system, defining a Rayleigh
      number closely analogous to that of a classical one-component Benard system.
      Values of this Rayleigh number at the onset of convection calculated from
      experimental data are found to have little temperature dependence, with an
      average value near that for a classical one-component fluid in this geometry. The
      Prandtl number is small and temperature dependent, with a smallest calculated
      value of 0.05.

PMID- 16592933
TI  - An empirical Bayes estimation problem.
AB  - Let x be a random variable such that, given theta, x is Poisson with mean theta,
      while theta has an unknown prior distribution G. In many statistical problems one
      wants to estimate as accurately as possible the parameter E(thetax = a) for some
      given a = 0,1,.... If one assumes that G is a Gamma prior with unknown parameters
      alpha and beta, then the problem is straightforward, but the estimate may not be
      consistent if G is not Gamma. On the other hand, a more general empirical Bayes
      estimator will always be consistent but will be inefficient if in fact G is
      Gamma. It is shown that this dilemma can be more or less resolved for large
      samples by combining the two methods of estimation.

PMID- 16592934
TI  - Structure of the body-centered cubic phase of lipid systems.
AB  - A new model is proposed for the structure of the body-centered cubic phase of
      lipid systems. Infinite rods of polar groups (and water) are arranged with axes
      parallel to the four cubic [unk]1 1 1[unk] directions. The hydrocarbon chains
      fill the space between the rods to form a continuous matrix. With this unified
      topology, the model explains satisfactorily the x-ray diffraction patterns of
      strontium soaps, lecithin, galactolipids, potassium soaps, and
      hexadecyltrimethylammonium bromide and explains the transition between
      cubic/H(II) phases. The paradoxical thermal effects on the lipid cubic phase, in
      particular the decrease of unit cell dimensions with increasing temperature, can
      be explained with the proposed model by mechanisms similar to those used for the
      monodimensional and bidimensional (mesomorphic) phases.

PMID- 16592935
TI  - Interaction between the intermediary electron acceptor (pheophytin) and a
      possible plastoquinone-iron complex in photosystem II reaction centers.
AB  - Photoreduction of the intermediary electron acceptor, pheophytin (Pheo), in
      photosystem II reaction centers of spinach chloroplasts or subchloroplast
      particles (TSF-II and TSF-IIa) at 220 K and redox potential E(h) = -450 mV
      produces an EPR doublet centered at g = 2.00 with a splitting of 52 G at 7 K in
      addition to a narrow signal attributed to Pheo([unk]) (g = 2.0033, DeltaH
      approximately 13 G). The doublet is eliminated after extraction of lyophilized
      TSF-II with hexane containing 0.13-0.16% methanol but is restored by
      reconstitution with plastoquinone A (alone or with beta-carotene) although not
      with vitamin K(1). TSF-II and TSF-IIa are found to contain approximately 2
      nonheme Fe atoms per reaction center. Incubation with 0.55 M LiClO(4) plus 2.5 mM
      o-phenanthroline (but not with 0.55 M LiClO(4) alone) decreases this value to
      approximately 0.6 and completely eliminates the EPR doublet, but photoreduction
      of Pheo is not significantly affected. Partial restoration of the doublet (about
      25%) was achieved by subsequent incubation with 0.2 mM Fe(2+), but not with
      either Mn(2+) or Mg(2+). The Fe removal results in the development of a
      photoinduced EPR signal (g = 2.0044 +/- 0.0003, DeltaH = 9.2 +/- 0.5 G) at E(h) =
      50 mV, which is not observed after extraction with 0.16% methanol in hexane. It
      is ascribed to plastosemiquinone no longer coupled to Fe in photosystem II
      reaction centers. The results show that a complex of plastoquinone and Fe can act
      as the stable "primary" electron acceptor in photosystem II reaction centers and
      that the interaction of its singly reduced form with the reduced intermediary
      acceptor, Pheo([unk]), is responsible for the EPR doublet.

PMID- 16592936
TI  - Vanadate inhibition of auxin-enhanced H secretion and elongation in pea epicotyls
      and oat coleoptiles.
AB  - In experiments carried out to investigate the acid secretion theory of auxin
      action, we utilized sodium orthovanadate, an agent found to be a selective
      inhibitor of a plasma membrane-associated H(+)-pumping ATPase in Neurospora
      [Bowman, B. J. & Slayman, C. W. (1979) J. Biol. Chem. 245, 2928-2934]. At 1 mM,
      vanadate inhibited auxin-enhanced medium acidification by pea epicotyl segments
      within 5 min, whether added 0.5 or 2.5 hr after auxin. Inhibition of
      acidification was total after 10-15 min but could be reversed within 10 min after
      vanadate removal. When given as a 40-min pretreatment, vanadate completely
      prevented any auxin-enhanced acidification. Vanadate inhibition of medium
      acidification by oat coleoptile segments was also total and reversible, but both
      inhibition and reversal occurred after longer lag times than in pea. Inhibitory
      effects of vanadate on elongation in pea and oat tissue closely paralleled its
      effects on acidification, and the inhibitory effect of vanadate on elongation
      could be reversed by an acidic buffer. Vanadate did not inhibit respiration or
      protein synthesis in pea epicotyl segments, although it strongly inhibited L
      [(14)C]leucine uptake. These results indicate the importance of cell wall
      acidification for short- and long-term auxin-enhanced growth and suggest the
      participation in wall acidification of a plasma membrane-associated ATPase acting
      as an H(+) pump.

PMID- 16592937
TI  - Calmodulin activation of plant microsomal Ca uptake.
AB  - The active ATP-dependent uptake of Ca(2+) into a plasma membrane-enriched
      microsomal fraction from plants is stimulated by the addition of plant as well as
      bovine brain calmodulin. This stimulation occurs only when the microsomes are
      prepared in the presence of EDTA. Plant calmodulin also activates the bovine
      brain 3',5'-cyclic-nucleotide phosphodiesterase (EC 3.1.4.17). Mitochondrial
      Ca(2+) accumulation is not affected by calmodulin. The calmodulin-mediated
      activation of microsomal Ca(2+) uptake is abolished by the antipsychotic drug
      fluphenazine, whereas the calmodulin-independent Ca(2+) uptake is only slightly
      decreased.

PMID- 16592938
TI  - A species near its equilibrium size in a fluctuating environment can evolve a
      lower intrinsic rate of increase.
AB  - In one specific model of a density-regulated population undergoing natural
      selection in a fluctuating environment there is a systematic evolutionary
      pressure favoring a lower intrinsic rate of increase, which can sometimes even
      overcome an evolutionary pressure favoring a higher carrying capacity.

PMID- 16592939
TI  - Density-dependent selection in a random environment: An evolutionary process that
      can maintain stable population dynamics.
AB  - A theoretical analysis of natural selection is presented in which fitnesses
      depend on population density and randomly varying environmental processes. The
      theory is based on a general, heuristic analysis of a pair of coupled, nonlinear,
      stochastic difference equations that describe the joint dynamics of allele
      frequencies and population size. Four main conclusions emerge from the
      investigation of a particular class of models: (i) growth rates at low population
      densities tend to increase; (ii) individual selection, given sufficient genetic
      flexibility, will mold growth rates at higher densities so that in spite of i,
      stable deterministic population dynamics are maintained; (iii) "more fit"
      genotypes cannot be simply characterized-in particular, the mean population size
      need not be increased; and (iv) genetic polymorphisms can be maintained in both
      haploid and diploid organisms.

PMID- 16592940
TI  - Effect of phenotypic variation on kin selection.
AB  - An expression for the equilibrium of the mean phenotypic value of a quantitative
      character is derived for a model in which the fitness of an individual depends on
      its own phenotype and the mean phenotypic value of a group of related
      individuals. When selection is weak the equilibrium mean is well predicted by
      Hamilton's k > 1/r rule (k is the ratio of mean fitness gained by recipient of
      altruistic behavior to mean fitness lost by donor; r is mean coefficient of
      relationship between donor and recipient). When selection is strong, however, the
      equilibrium mean depends on the heritability of the character. Low heritability
      can lead to substantially more "altruism" than predicted by the k > 1/r rule.

PMID- 16592941
TI  - Beta limits for torsatrons.
AB  - An ideal magnetohydrodynamic equilibrium and stability code is used to study
      ballooning modes in torsatrons. The most dangerous modes turn out to be those
      with low poloidal and toroidal wave numbers. Beta limits for equilibrium and
      stability are determined for an [unk] = 2 ultimate torsatron with large [unk] = 1
      and [unk] = 3 sidebands.

PMID- 16592942
TI  - Ring contraction of hydroporphinoid to corrinoid complexes.
AB  - Crystalline nickel(II) and dicyanocobalt(III) complexes of a racemic
      1,2,2,7,7,12,12,17,17,20-decamethyl-20-hydroxy-1,2,3,7,8,12,13,20-octahydro- 17H
      porphyrin rearrange to the corresponding complexes of racemic 19-acetyl
      1,2,2,7,7,12,12,17,17-nonamethyl-trans-corrin on melting (approximately 290
      degrees C and 260 degrees C, respectively). The nickel(II) 19-acetylcorrinate
      formed in this way is shown to deacetylate to racemic nickel(II)
      1,2,2,7,7,12,12,17,17-nonamethyl-trans-corrinate on treatment with 2 M KOH. These
      reactions are being studied as potentially biomimetic chemical models for the
      elusive ring contraction step in vitamin B(12) biosynthesis.

PMID- 16592943
TI  - On the importance of changes in the gravity field on seismic recording at
      ultralong periods.
AB  - The effect of changes in gravity induced by the Earth's deformation on seismic
      recording at ultralong periods is studied quantitatively for the low-order
      spheroidal modes of the Earth. Because this effect can either enhance or reduce
      the recorded amplitude of a mode, depending on its geometry, it may become
      nontrivial at the longest free-oscillation periods, and contribute to relative
      deviations of up to 17%.

PMID- 16592944
TI  - Random walk theory of a trap-controlled hopping transport process.
AB  - A random walk theory of hopping motion in the presence of a periodic distribution
      of traps is presented. The solution of the continuous-time random walk equations
      is exact and valid for arbitrary intersite interactions and trap concentration.
      The treatment is shown to be equivalent to an exact solution of the master
      equation for this trapping problem. These interactions can be a general function
      of electric field and are not restricted to nearest neighbors. In particular,
      with the inclusion of trap-to-trap interactions, as well as trap-to-host
      interactions, an exact treatment of the change from one hopping channel to
      another has been obtained. The trap-modulated propagator has been derived in
      terms of a type of Green's function that is introduced. The results are
      specialized to spatial moments of the propagator, from which expressions for the
      drift velocity and diffusion coefficient are obtained. Numerical results for the
      drift velocity are presented and shown to account for the change in hopping
      channels in recent transport measurements in mixed molecularly doped polymers.

PMID- 16592945
TI  - Mechanism of tobacco mosaic virus assembly: Incorporation of 4S and 20S protein
      at pH 7.0 and 20 degrees C.
AB  - The mechanism of assembly of tobacco mosaic virus (TMV) has been investigated at
      pH 7.0 and 20 degrees C by analytical ultracentrifugation. Under these conditions
      the overall rates of interconversion of 4S and 20S TMV coat protein are
      sufficiently slow to make possible measurements of the concentrations of
      remaining 4S and 20S TMV coat protein after addition of homologous RNA to
      solutions containing, initially, various mass ratios of 20S protein to 4S
      protein. It has been possible to measure, by schlieren boundary analysis, the
      relative rates of incorporation of 4S and 20S TMV protein into the growing
      nucleoprotein rod over the range of initial 20S:4S protein mass ratios from 93:7
      to 18:82. The results show that the amount of incorporation of 20S TMV protein
      depends on the initial 20S:4S mass ratio between approximately 100% and 60% 20S
      protein but that reconstitution can proceed with approximately 100% 20S TMV
      protein to form full virus-size rods. However, when the initial protein solutions
      have less than 60% 20S protein, approximately 80% of the reconstituted
      nucleoprotein is preferentially formed from 4S coat protein. The remaining
      approximately 20% appears to require preformed 20S coat protein. These results
      suggest that a larger region of RNA than previously estimated is involved in the
      rate-limiting nucleation step in assembly and may explain previously conflicting
      results concerning the elongation phase of assembly when starting with partially
      assembled rods.

PMID- 16592946
TI  - Replacement of riboflavin by an analogue in the blue-light photoreceptor of
      Phycomyces.
AB  - Under suitable conditions, roseoflavin [7-methyl-8-dimethylamino-10-(1'-D
      ribityl)isoalloxazine] replaces riboflavin to about 80% in the photoreceptor of
      Phycomyces. The substitute-bearing photoreceptor functions with an efficiency of
      about 0.1% of that of the normal receptor. The substitution is proven by (i) a
      decrease of the effective light flux by a factor of 4.7, expressed as a
      corresponding increase in threshold, and (ii) an increase of the effectiveness of
      529-nm light relative to 380-nm light. It has also been shown that roseoflavin is
      taken up by the mycelium, translocated to the sporangiophore, and effectively
      phosphorylated by the riboflavin kinase of Phycomyces.

PMID- 16592947
TI  - Magnetic order and energetics of dipolar coupling in magnetic superconductors.
AB  - The exact (not just nearest-neighbor) dipolar coupling energy densities for the
      observed structures of the rare earth Chevrel compounds are calculated by the
      method of Luttinger and Tisza. The dipolar coupling energy density for the most
      probable spin configuration is comparable to the observed magnetic transition
      temperature, T(M), but the most probable ground state is not found
      experimentally. The discrepancy between the observed magnetic ground state and
      that predicted from dipole coupling may arise from conduction electron effects or
      possibly from some strong crystal field effect and should be included in any
      electronic theory of the superconductive state below T(M).

PMID- 16592948
TI  - Chemical potential of bound ligand, an important parameter for free energy
      transduction.
AB  - The chemical potential (mu(L,b)) of a ligand L bound to a protein or enzyme can
      be rigorously defined, and this paper describes some of its properties in
      relation to other thermodynamic parameters, with emphasis on thermodynamic
      parameters that may be used in the elucidation of the mechanism of biological
      free energy transduction. Free energy transduction involves the transfer of free
      energy from one molecule to another, and the actual transfer may often occur
      while both molecules are bound to the transducer enzyme, which means that mu(L,b)
      for one bound ligand increases at the expense of mu(L,b) for the other. The free
      energy change for the overall reaction may be very small, and it is not possible
      to express the phenomenon of transfer, in thermodynamic terms, without the
      explicit use of mu(L,b) as a parameter.

PMID- 16592949
TI  - Intermediates of a polynuclear manganese center involved in photosynthetic
      oxidation of water.
AB  - Electron paramagnetic resonance of spinach chloroplasts given a series of laser
      flashes, n = 0, 1,..., 6, at room temperature and rapidly cooled to -140 degrees
      C reveals a signal possessing at least 16 and possibly 21 or more hyperfine lines
      when observed below 35 K. The spectrum is consistent with a pair of
      antiferromagnetically coupled Mn ions, or possibly a tetramer of Mn ions, in
      which Mn(III) and Mn(IV) oxidation states are present. The intensity of this
      signal peaks on the first and fifth flashes, suggesting a cyclic change in
      oxidation state of period 4. The multiline signal produced on the first flash is
      not affected by the electron transport inhibitor 3-(3,4-dichlorophenyl)-1,1
      dimethylurea but is abolished by agents that influence the state of bound
      manganese, such as incubation with alkaline Tris, or dithionite, and by
      extraction with cholate detergent in the presence of ammonium sulfate. These
      results indicate that the paramagnetic signal is monitoring oxidation state
      changes in the enzyme involved in oxidation of water.

PMID- 16592950
TI  - Formation of hybrid complexes between Ca and the ionophores bromolasalocid (Br
      X537A) and A23187.
AB  - The ionophores A23187 and bromolasalocid (Br-X537A) acted synergistically in
      translocating Ca(2+) from an aqueous into an organic immiscible phase or in
      mediating Ca(2+) transport across the organic phase, the effects obtained in the
      simultaneous presence of both ionophores being greater than those expected from a
      summation of the individual effects of each ionophore. The nuclear magnetic
      resonance spectrum obtained when the complexation of Ca(2+) occurred in the
      presence of both ionophores differed strikingly from the individual spectra
      obtained with the A23187-Ca and Br-X537A-Ca complexes. These findings indicate
      that the two ionophores are able to form hybrid complexes with Ca(2+).

PMID- 16592951
TI  - Phytochrome induces photoreversible calcium fluxes in a purified mitochondrial
      fraction from oats.
AB  - Previous studies have indicated that phytochrome regulates Ca(2+) fluxes across
      the plasma membrane of plant cells. In this study we investigated whether
      phytochrome can also regulate such fluxes across mitochondrial membranes, using
      the Ca(2+)-sensitive dye murexide to monitor the uptake and release of Ca(2+) by
      mitochondria. The results showed that Ca(2+) fluxes in these organelles could be
      photoreversibly altered, red light diminishing the net uptake rate and far-red
      light restoring this rate to its dark control level. Treatment of the
      mitochondria with ruthenium red blocked their Ca(2+) uptake. In the presence of
      this inhibitor, red light induced a net efflux of Ca(2+) from the mitochondria,
      and subsequent far-red light reduced this efflux to nearly zero, the dark control
      level. Light-induced rate changes in Ca(2+) flux, both with and without the
      inhibitor, persisted for several minutes in the dark and remained photoreversible
      through several irradiations for as long as 30 min. The purity of the
      mitochondrial preparation was judged to be about 80% by electron microscopic
      morphometry; most of the phytochrome present was localized on the mitochondria in
      the preparation by using immunocytochemical methods. Taken together with previous
      findings, the results suggest that red light activation of phytochrome would
      initiate an increase in the cytosolic Ca(2+) concentration. The results are
      integrated with the fact that calmodulin is a component of plant cell cytoplasms
      to construct a model postulating that phytochrome directs photomorphogenesis in
      part through its regulation of Ca(2+) and calmodulin-controlled enzyme
      activities.

PMID- 16592952
TI  - Some heat engine cycles in which liquids can work.
AB  - Liquids can work in heat engine cycles that employ regeneration. Four such cycles
      are discussed: Stirling, Malone, Stirling-Malone, and Brayton. Both regeneration
      and the role of the second thermodynamic medium are treated, and the principles
      are verified by quantitative measurements with propylene in a Stirling-Malone
      cycle.

PMID- 16592953
TI  - Sequence arrangement of a highly methylated satellite DNA of a plant, Scilla: A
      tandemly repeated inverted repeat.
AB  - G+C-rich satellite DNA, representing about 19% of total nuclear DNA, was isolated
      from various tissues of the monocotyledonous plant, Scilla siberica, by using
      Ag(+)-Cs(2)SO(4) gradient techniques. This satellite DNA had an unusually high
      melting point and a high methylcytosine (m(5)C) content ( approximately 25% of
      total bases; m(5)C/cytosine ratio approximately 1.5) and was localized, by in
      situ hybridization, in the heterochromatin regions of the chromosomes. Digestion
      with restriction endonuclease Hae III yielded a series of fragments ranging from
      35 to several hundred nucleotide pairs. The major fragments, I-IV (35, 50, 59,
      and 69, nucleotide pairs, respectively), were isolated, and their nucleotide
      sequences were determined. The dominant fragment I was a highly symmetrical
      molecule, with a basically palindromic arrangement. This sequence represented the
      basic unit of Scilla satellite DNA and was tandemly repeated many times, with
      some base substitutions and multiple successive insertions of the tetranucleotide
      G-T-C-C. The dinucleotide CpG was the commonest nearest-neighbor sequence. Thin
      layer chromatography, DNA sequence analysis, and gas chromatography combined with
      mass spectrometry showed the high m(5)C content (m(5)C/Cyt = 2.2 and 2.8,
      respectively, for fragments II and III). Identical cleavage fragments were found
      in satellite DNAs from two other species of this genus (S. amoena and S.
      ingridae), which suggests that this constitutively methylated sequence is
      evolutionarily stable. The sequence arrangement of this plant satellite DNA is
      compared with those reported for several animal satellite DNAs.

PMID- 16592954
TI  - Serologically distinguishable alterations in the molecular specificity of cell
      cohesion during morphogenesis in Dictyostelium discoideum.
AB  - Cells of the mutant strain JC-5 of the slime mold Dictyostelium discoideum
      exhibit at a specific, late developmental stage a temperature-sensitive
      morphogenetic defect associated with the loss of cell cohension. We show that at
      the restrictive temperature, the loss of cohesion and attendant dispersal of
      multicellular aggregates is associated with the disappearance or sequestration of
      a plasma membrane-bound moiety capable of reacting with and, hence, absorbing
      cohesion-blocking Fab. At the permissive temperature, the maintenance of
      cohesiveness past the critical stage or the recovery of lost cohesiveness is
      correlated with the presence or reappearance of the Fab-reactive moiety.This
      moiety is absent or sterically incapable of reaction with Fab preparations at an
      earlier developmental stage in either mutant or wild-type cells-i.e., at a time
      when they have just entered into multicellular aggregates. Conversely, a
      serologically distinguishable membrane-bound moiety present in the early mutant
      or wild-type cells, whose reaction with homologous Fab also precludes their
      cohesion, is absent or serologically unreactive in either mutant or wild-type
      cells that are at comparable late developmental stages. We conclude that the
      cohesive moiety responsible for initiation of cell aggregates is supplanted by or
      transformed into a serologically distinct, cohesive complex responsible for the
      maintenance of the aggregate's integrity through the later stages of development.

PMID- 16592955
TI  - On the dynamics of the Ising model of cooperative phenomena.
AB  - A two-dimensional (and to some degree three-dimensional) version of Glauber's one
      dimensional spin relaxation model is described. The model is constructed to yield
      the Ising model of cooperative phenomena at equilibrium. A complete hierarchy of
      differential equations for multispin correlation functions is constructed. Some
      remarks are made concerning the solution of them for the initial value problem of
      determining the relaxation of an initial set of spin distributions.

PMID- 16592956
TI  - Three-state, steady-state Ising systems: Monte Carlo and Bragg-Williams
      treatments.
AB  - In two earlier papers, the steady-state critical and phase-transition properties
      of a lattice of three-state enzyme molecules were studied by using the "closed"
      Bragg-Williams (BW), or mean field, approximation. The "open" BW and Monte Carlo
      methods are applied to the same problem in this paper by using finite lattices.
      The open BW treatment provides a way of locating the cut across a van der Waals
      type of loop encountered in a phase transition in the closed BW system.
      Thermodynamic-like methods cannot be used for this purpose as they can with two
      state, steady-state systems.

PMID- 16592957
TI  - Leaf folding in a sensitive plant: A defensive thorn-exposure mechanism?
AB  - Quantitative photographic evidence is presented indicating that in the sensitive
      plant Schrankia microphylla the leaf-folding response that accompanies the
      sensitive reaction results in a pronounced increase in thorn exposure. It is
      argued that in sensitive plants that are thorny, including other species of
      Schrankia, as well as Mimosa pudica, the plant in which the sensitive reaction is
      traditionally demonstrated, leaf folding may be a defensive adaptation.

PMID- 16592958
TI  - Introduction of transposon Tn5 into Myxococcus for analysis of developmental and
      other nonselectable mutants.
AB  - The transposon Tn5, which carries a gene for kanamycin resistance, can be
      introduced into Myxococcus xanthus, an organism that undergoes a primitive cycle
      of development, from Escherichia coli by the specialized transducing phage
      P1::Tn5. Tn5 DNA sequences, but no P1 sequences, are found in the stable
      kanamycin-resistant transductants. Tn5 transposes from P1 to many different
      chromosomal sites in Myxococcus. In each independent transductant of Myxococcus
      examined, the Tn5 element is found in a different DNA fragment produced by
      cleaving cell DNA with a restriction endonuclease. Moreover, different Tn5
      insertions have been found linked to the first 20 different genetic sites tested.
      Once inserted into the Myxococcus chromosome, Tn5 remains fixed in position
      during growth and when transferred to another strain by generalized transduction.
      To analyze developmental or other mutants that have no selectable phenotype
      themselves, a general method has been devised, and tested, for the systematic
      isolation of a Tn5 insertion near any arbitrary locus.

PMID- 16592959
TI  - Multivariate analysis of Drosophila courtship.
AB  - Courtship records of 15 pairs of Drosophila melanogaster were analyzed for
      temporal stationarity of courtship behaviors, behavioral diversity, behavioral
      intercorrelations, sequential properties, and information transmission for both
      sexes. Durations of one male behavior, "orient-back," and two female behaviors,
      "preen" and "stand still," were found to change from the first to the second half
      of courtship. Male diversity was greater than female diversity, and both were
      stationary over time. Correlation analyses failed to single out any particular
      male or female behaviors as being influential in controlling courtship duration.
      Male behavior sequences formed several multibehavior loops; female behavior
      consisted of only a few terminal two-tuple transitions. Transmission analysis
      carried out on the joint male/female transition matrix showed a higher
      transmission rate from males to females (12%) than from females to males (7%).
      Potential applications of this multivariate analysis to investigations of
      neurobiological and evolutionary aspects of Drosophila courtship behavior are
      proposed.

PMID- 16592960
TI  - One-trial associative learning modifies food odor preferences of a terrestrial
      mollusc.
AB  - We present evidence of rapid and reliable associative learning by the terrestrial
      mollusc, Limax maximus. Slugs were exposed once to a pairing of a highly
      attractive food odor (potato or carrot) and a saturated solution of quinidine
      sulfate, a bitter-tasting plant substance. In comparison with control slugs, the
      exposed slugs subsequently displayed a markedly reduced preference for the odor
      paired with quinidine. This reduced odor preference was limited to the specific
      odor paired with quinidine and did not generalize to other food odors.

PMID- 16592961
TI  - Enzymatic hydrolysis of cellulose: Visual characterization of the process.
AB  - Cellulose from the Gram-negative bacterium Acetobacter xylinum has been used as a
      model substrate for visualizing the action of cellulase enzymes from the fungus
      Trichoderma reesei. High-resolution electron microscopy reveals that A. xylinum
      normally produces a ribbon of cellulose that is a composite of bundles of
      crystalline microfibrils. Visual patterns of the process of cellulose degradation
      have been established. Enzymes are initially observed bound to the cellulose
      ribbon. Within 10 min, the ribbon is split along its long axis into bundles of
      microfibrils which are subsequently thinned until they are completely dissolved
      within 30 min. Incubations with purified components of the cellulase enzyme
      system produced less dramatic changes in ribbon structure. Purified 1,4-beta-D
      glucan cellobiohydrolase I (D) (EC 3.2.1.91) produced no visible change in
      cellulose structure. Purified endo-1,4-beta-D-glucanase IV (EC 3.2.1.4) produced
      some splaying of ribbons into microfibril bundles. In both cases, whole ribbons
      were present even after 60 min of incubation, visually confirming the synergistic
      mode of action of these enzymes.

PMID- 16592962
TI  - Structural brain mutant of Drosophila melanogaster with reduced cell number in
      the medulla cortex and with normal optomotor yaw response.
AB  - KS58, one out of six known alleles of the small optic lobes (sol) gene in
      Drosophila melanogaster, reduces the cell number in the medulla cortex by
      degeneration of ganglion cells in the pupae to about 50%. Also, about half the
      volume of the medulla and lobula complex neuropils is missing. Many Golgistained
      cells in the mutant optic lobes resemble their homologues in wild type. However,
      special classes of transmedullary columnar neurons projecting to the lobula or to
      both lobula and lobula plate are not seen in the mutant. Some neurons linking the
      lobula complex to the central brain send branches to the medulla (the branches do
      not exist in wild type); some other types seem to be missing. The fate mapping of
      the KS58 focus reveals a location ventral to the head bristles and in sine oculis
      (so) flies the mutation further reduces the rudiments of the optic lobes normally
      seen. Therefore the sol phenotype is not induced by mutant eyes and the primary
      gene action seems to be on nervous tissue. The structural alterations of the
      small optic lobes are reflected in visual orientation behavior. The optomotor yaw
      response, however, is almost quantitatively preserved. The respective neural
      network should still be present in the mutant optic lobes.

PMID- 16592963
TI  - A multilocus estimator of mating system parameters in plant populations.
AB  - A multilocus method of estimating mating system parameters in populations is
      presented that recovers information from classification over multiple loci that
      single-locus estimators do not detect. It is shown that the multilocus estimator
      provides a standard of reference (null hypothesis) that can be useful in
      analyzing the effects of factors such as population heterogeneity and post-mating
      zygotic selection on the transmission of genetic information at the population
      level.

PMID- 16592964
TI  - Trade-off between r-selection and K-selection in Drosophila populations.
AB  - Density-dependent genetic evolution was tested in experimental populations of
      Drosophila melanogaster subject for eight generations to natural selection under
      high (K-selection) or low (r-selection) population density regimes. The test
      consisted of determining at high and at low densities the per capita rate of
      population growth of the selected populations. At high densities, the K-selected
      populations showed a higher per capita rate of population growth than did r
      selected populations, but the reverse was true at low densities. These results
      corroborate the predictions derived from formal models of density-dependent
      selection. However, no evidence of a trade-off in per capita rate of growth was
      observed in 25 populations of D. melanogaster, each homozygous for a different
      second chromosome sampled from a natural population.

PMID- 16592965
TI  - Sex choice and the size advantage model in jack-in-the-pulpit (Arisaema
      triphyllum).
AB  - Arisaema triphyllum is a perennial herb whose sex and size often change from one
      growing season to the next. The proportional gain in reproductive success (RS)
      with size is much greater for female (carpellate) plants than it is for male
      (staminate) plants. I constructed RS-size curves for males and females; the
      curves intersect at a point t = 398 mm. According to theory derived from the size
      advantage model, t is the point below which the plants should be male and above
      which they should be female. Plots of size-frequency distributions of males and
      females show that below 380 mm the proportion of males is greater than the
      proportion of females, whereas above that point the proportion of females is
      greater than the proportion of males. Thus prediction and observed results are in
      very close conformity.

PMID- 16592966
TI  - Symmetry breaking and pattern selection in far-from-equilibrium systems.
AB  - A mechanism enabling nonequilibrium systems to select spatially asymmetric
      solutions is outlined. It operates when a macroscopic mode undergoing a symmetry
      breaking bifurcation can interact with a polar or a chiral field not explicitly
      involved in the bifurcation. The perturbation of the bifurcation induced by the
      field allows the system to capture the external asymmetry and build patterns of
      preferred polarity or preferred chirality. The chemical and biological
      implications of forming such an asymmetric medium are discussed.

PMID- 16592967
TI  - Extended x-ray absorption fine structure of copper in cytochrome c oxidase:
      Direct evidence for copper-sulfur ligation.
AB  - The copper x-ray fluorescence excitation spectrum of cytochrome c oxidase
      (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) has been recorded in the
      245-270 K range. The beat pattern observed in the extended x-ray absorption fine
      structure can be accounted for only by postulating a combination of sulfur and
      nitrogen (or oxygen) ligands to the copper. The average Cu-S distance is 2.27 +/-
      0.02 A and the average Cu-N (or Cu-O) distance is 1.97 +/- 0.02 A. The amplitudes
      require ca, 1-1.5 sulfurs and 2 nitrogens (or oxygens) per copper. The
      distribution of sulfur ligands between Cu(A) and Cu(B) sites is not known,
      although there is some evidence that two sulfur atoms are bound to Cu(A).

PMID- 16592968
TI  - Structure and chemistry of a metal cluster with a four-coordinate carbide carbon
      atom.
AB  - Molecular metal clusters with carbide carbon atoms of low coordination number
      have been prepared; they are the anionic [HFe(4)C(CO)(12) (-)] and
      [Fe(4)C(CO)(12) (2-)] clusters. An x-ray crystallographic analysis of a
      tetraaminozinc salt of the latter has established a butterfly array of iron atoms
      with the carbide carbon atom centered above the wings of the Fe(4) core. Each
      iron atom was bonded to three peripheral carbonyl ligands. The distances from the
      carbide carbon to iron were relatively short, particularly those to the apical
      iron atoms (1.80 A average). Protonation of the anionic carbide clusters
      reversibly yielded HFe(4)(CH)(CO)(12), and methylation of the dianion gave
      {Fe(4)[CC(O)CH(3)](CO)(12) (-)}. Oxidation of [Fe(4)C(CO)(12) (2-)] yielded the
      coordinately unsaturated Fe(4)C(CO)(12) cluster, which was extremely reactive.
      Hydrogen addition to this iron cluster was rapid below 0 degrees C, and a C-H
      bond was formed in this transformation.

PMID- 16592969
TI  - Solution conformation of gramicidin S: An intramolecular nuclear Overhauser
      effect study.
AB  - The solution conformation of gramicidin S in deuterated dimethyl sulfoxide was
      investigated by using the intramolecular nuclear Overhauser effect experiment.
      Experimental Overhauser enhancements were compared with predicted values for each
      of the nine most-stable conformations (M1-M9) calculated by Dygert et al. on the
      basis of energy-minimization procedures [Dygert, M., Go, N. & Scheraga, H. A.
      (1975) Macromolecules 8, 750-761]. By using statistical hypothesis testing, the
      three lowest-energy conformations (M1, M2, and M3) were shown to give the best
      fit with the experimental data. All other conformations (M4-M9) were found to be
      inconsistent with the experimental data.

PMID- 16592970
TI  - Molecular organization in micelles and vesicles.
AB  - The configurations of the hydrocarbon chains in micelles are severely constrained
      by the space-filling requirements of the chain segments, by the continuity of the
      chains, and by the micellar geometry. A statistical theory that takes full
      account of these constraints is developed by using a lattice model. The chain
      ends are deduced to be nonuniformly distributed, with maximal incidence
      approximately midway between the center of the micelle and the outer surface.
      Whereas the chain disorder near the outside of the hydrophobic core may approach
      that of a liquid, crowding of the chains near the core center imposes a degree of
      order approaching that in a crystal. These results are at variance with the
      prevailing view that the micellar interior resembles a "liquid hydrocarbon
      droplet." Also discussed are the effects of curvature on the chain configurations
      in monolayers and bilayers. It is found, for example, that the "disorder
      gradients" in inner and outer half-bilayers of small vesicles should be
      substantially different. Implications of these results are discussed.

PMID- 16592971
TI  - Conformation of cyclo(Gly-L-Pro-L-Pro-Gly-L-Pro-L-Pro)(2)Mg complex crystallized
      from CH(3)CN solution.
AB  - The cyclic hexapeptides (Gly-L-Pro-L-Pro-Gly-L-Pro-L-Pro) in the (peptide-Mg
      peptide)(2+) complex have nearly identical asymmetric conformations. Each has two
      cis Pro-Pro linkages and lacks any intraring hydrogen bonds. The Mg(2+) ion forms
      six ligands in a regular octahedral array with the carbonyl oxygen atoms of the
      two Gly residues and one Pro residue of each peptide. The "sandwich" complex has
      an approximate 2-fold rotation axis through the Mg(2+) relating the two peptide
      moieties. Cyclo(Gly-Pro-Pro-Gly-Pro-Pro)(2)Mg(ClO(4))(2). 4C(2)H(3)CN
      crystallizes in space group P3(1) with a = b = 15.744(4) A, c = 24.002(6) A,
      gamma = 120 degrees , and Z = 3. A highlight of the structure determination is
      the ready location of the Mg self-vector in a Harker section and the development
      of the entire structure by use of the tangent formula starting with the known
      position of the Mg atom.

PMID- 16592972
TI  - Nonbonded interaction potentials in methyl-substituted butanes, obtained from
      high-energy overtone spectra.
AB  - The observed decrease in local mode anharmonicity with increasing methyl
      substitution in butane is related to a change in potential energy along a methyl
      CH-stretching coordinate. The potential energy change is modeled by Lennard-Jones
      6-12 and Morse potentials and the resultant potential parameters are discussed.

PMID- 16592973
TI  - A construction of F(1) as automorphisms of a 196,883-dimensional algebra.
AB  - In this note, I announce the construction of the finite simple group F(1), whose
      existence was predicted independently in 1973 by Bernd Fischer and by me. The
      group has order 2(46)3(20)5(9)7(6)11(2)13(3)17.19.23.29.31.41. 47.59.71 =
      808,017,424,794,512,875,886,459,904,961,710,757,005,754,368,000,000,000 and is
      realized as a group of automorphisms of a 196,883-dimensional commutative
      nonassociative algebra over the rational numbers, which has an associative form.
      Equivalently, it is a group of automorphisms of a cubic form in 196,883
      variables. It turns out that all the relevant arguments and calculations may be
      done by hand. Furthermore, existence of the group F(1) implies the existence of a
      number of other sporadic simple groups for which existence proofs formerly
      depended on work with computers. We are beginning to look upon this group as a
      "friendly giant."

PMID- 16592974
TI  - Enumeration of structure-sensitive graphical subsets: Theory.
AB  - THE NECESSARY MATHEMATICAL MACHINERY IS DEVELOPED FOR ENUMERATION OF THE
      FOLLOWING TYPES OF SPECIAL SUBSETS OF THE VERTICES OR EDGES OF A GENERAL GRAPH:
      (i) independent sets, (ii) connected sets, (iii) point and line covers, (iv)
      externally stable sets, (v) kernels, and (vi) irredundant sets.

PMID- 16592975
TI  - A Gauss measure on the set of interval exchange transformations.
AB  - An interval exchange transformation is a piece-wise order-preserving isometry of
      a finite interval. In previous works the author has reduced certain questions
      about interval exchange transformations to questions about the ergodic behavior
      of a related class of transformations, with domain the body of all interval
      exchange transformations. The latter questions can be answered with the aid of
      Gauss measures for the related transformations; by Gauss measure is understood a
      conservative, ergodic invariant measure whose density is a rational function. The
      present note describes the construction of such Gauss measures.

PMID- 16592976
TI  - Equipartition of energy for higher-order hyperbolic equations.
AB  - Let A(0), A(1),...,A(2(N)-1) be commuting skew-adjoint operators on a Hilbert
      space [unk]. Then the equation Pi(j=0) (2(N)-1) (d/dt - A(j))v(t) = 0 (t real)
      admits equipartition of energy [in the sense that the jth partial energy E(j)(t)
      of any solution at time t satisfies lim(t-->+/-infinity)E(j)(t) = 2(-N).(total
      energy) for each of the 2(N) values of j] if and only if the closure B(jk) of
      A(j) - A(k) satisfies weak-operator-limit exp(tB(jk)) = 0 as t --> +/-infinity
      whenever j not equal k.

PMID- 16592977
TI  - The Rogers-Ramanujan identities: Lie theoretic interpretation and proof.
AB  - The two Rogers-Ramanujan identities, which equate certain infinite products with
      infinite sums, are among the most intriguing of the classical formal power series
      identitites. It has been found by Lepowsky and Milne that the product side of
      each of them differs by a certain factor from the principally specialized
      character of a certain standard module for the Euclidean Kac-Moody Lie algebra
      A(1) ((1)). On the other hand, the present authors have introduced an infinite
      dimensional Heisenberg subalgebra [unk] of A(1) ((1)) which leads to a
      construction of A(1) ((1)) in terms of differential operators given by the
      homogeneous components of an "exponential generating function." In the present
      announcement, we use [unk] to formulate a natural "abstract Rogers-Ramanujan
      identity" for an arbitrary standard A(1) ((1))-module which turns out to coincide
      with the classical identities in the cases of the two corresponding standard
      modules. The abstract identity equates two expressions, one a product and the
      other a sum, for the principally specialized character of the space Omega of
      highest weight vectors or "vacuum states" for [unk] in the module. The
      construction of A(1) ((1)) leads to a concrete realization of Omega as the span
      of certain spaces of symmetric polynomials occurring as the homogeneous
      components of exponential generating functions. The summands in the Rogers
      Ramanujan identities turn out to "count" the dimensions of these spaces. For
      general standard A(1) ((1))-modules, we conjecture that the abstract identities
      agree with generalizations of the Rogers-Ramanujan identities due to Gordon,
      Andrews, and Bressoud.

PMID- 16592978
TI  - Visible absorption spectrum of liquid ethylene.
AB  - The visible absorption spectrum of liquid ethylene at approximately 108 K from
      5500 A to 7200 A was measured by using a pulsed tunable dye laser, immersed
      transducer, gated-detection opto-acoustic spectroscopy technique. The absorption
      features show the strongest band with an absorption coefficient of approximately
      2 x 10(-2) cm(-1) and the weakest band with an absorption coefficient of
      approximately 1 x 10(-4) cm(-1). Proposed assignments of the observed absorption
      peaks involve combinations of overtones of local and normal modes of vibration of
      ethylene.

PMID- 16592979
TI  - Bacterial bioluminescence: Spectral study of the emitters in the in vitro
      reaction.
AB  - Transient fluorescent species are observed in the bioluminescent reactions of
      three reduced flavin mononucleotides with aliphatic aldehydes and oxygen,
      catalyzed by bacterial luciferase. In each case the fluorescence spectral
      distribution is similar to that of the bioluminescence but is readily
      distinguishable from it on the basis of a significantly greater signal strength.
      The corrected bioluminescence maxima using Beneckea harveyi luciferase are 479 nm
      (iso-FMNH(2)), 490 nm (FMNH(2)), and 560 nm (2-thio-FMNH(2)). In an ethanol glass
      at 77 K, 2-thioriboflavin is fluorescent (varphi(F) = 0.03, lambda(max) = 562
      nm). These results are interpreted by a sensitized chemiluminescence mechanism in
      which the flavins bound to luciferase act as acceptors of excitation energy. For
      2-thio-FMNH(2), this acceptor species appears to be the oxidized 2-thio-FMN on
      the basis of the spectral evidence, whereas for the other flavins, some form of
      reduced species is a more likely candidate.

PMID- 16592980
TI  - Energies and kinetics of radical pairs involving bacteriochlorophyll and
      bacteriopheophytin in bacterial reaction centers.
AB  - Absorbance changes reflecting the formation of a transient radical-pair state,
      P(F), were measured in reaction centers from Rhodopseudomonas sphaeroides under
      conditions that blocked electron transfer to a later carrier (a quinone, Q). The
      temperature dependence of the absorbance changes suggests that P(F) is an
      equilibrium mixture of two states, which appear to be mainly
      (1)[P([unk])B([unk])] and (1)[P([unk])H([unk])]. P is a bacteriochlorophyll
      dimer, B is a bacteriochlorophyll absorbing at 800 nm, and H is a
      bacteriopheophytin. In the presence of Q([unk]), the energy of
      (1)[P([unk])B([unk])] is about 0.025 eV above that of (1)[P([unk])H([unk])],
      (1)[P([unk])H([unk])] can decay to a triplet state, P(R), which also is an
      equilibrium mixture of two states, separated by about 0.03 eV. The lower of these
      appears to be mainly a locally excited triplet state of P, (3)P; the upper state
      contains a major contribution from a triplet charge-transfer state,
      (3)[P([unk])B([unk])]. The temperature dependence of delayed fluorescence from
      P(R) indicates that (3)P lies 0.40 eV below the excited singlet state, P(*),
      which is about 0.05 eV above (1)[P([unk])H([unk])]. The (1,3)[P([unk])B([unk])]
      charge-transfer states thus appear to interact with the locally excited states of
      P and B to give singlet and triplet states that are separated in energy by about
      0.35 eV. This is 10(6) times larger than the splitting between
      (1)[P([unk])H([unk])] and (3)[P([unk])H([unk])] and implies strong orbital
      overlap between P([unk]) and B([unk]). This is consistent with recent picosecond
      studies which suggest that electron transfer from P(*) to B occurs within 1 ps
      and is followed in 4 to 10 ps by electron transfer from B([unk]) to H.

PMID- 16592981
TI  - Continuous fluorescence microphotolysis: A sensitive method for study of
      diffusion processes in single cells.
AB  - Continuous fluorescence microphotolysis is a sensitive method for the study of
      translational diffusion in the plasma membrane of single living cells and related
      systems. In this communication the conceptual basis of the method and its
      theoretical framework and experimental realization, as well as applications, are
      reported. In continuous fluorescence microphotolysis a microscopic membrane area
      of a single fluorescently labeled cell is irradiated by a laser beam while the
      fluorescence emitted from the area is monitored. The decay of the measuring
      signal reflects the competition of two processes: (i) the elimination of
      fluorophores by irreversible photolysis, and (ii) the entrance of new
      fluorophores into the area by diffusion. Rate constants for the two processes can
      be derived from the measuring data by mathematical analysis. As compared to our
      initial approach, fluorescence microphotolysis [Peters, R., Peters, J., Tews, K.
      H. & Bahr, W. (1974) Biochim. Biophys. Acta 367, 282-294], the main advantage of
      the method described here is an improvement of data quality and detection limit
      by orders of magnitude. From the practical point of view the main advantage is a
      simplification of the experimental setup. Results obtained by this method are
      encouraging and support the contention that continuous fluorescence
      microphotolysis may disclose new aspects of diffusion processes in biological
      systems.

PMID- 16592982
TI  - Stochastic flows in integral and fractal dimensions and morphogenesis.
AB  - The effect of dimensionality and spatial extent on the dynamics of an
      irreversible reaction confined to a finite system was studied by a Monte Carlo
      simulation. Stochastic flows on surfaces of integral and fractal dimensions and
      the consequences of reducing the dimensionality of the reaction space are
      described. As regards the timing and efficiency of chemical reactions in small
      systems, our simulations show that placing the reactive site at a central
      location may be favored at an early stage of growth but, as the system evolves in
      size, a location on the boundary becomes favored. The possible relevance of these
      calculations to the problem of morphogenesis is brought out.

PMID- 16592983
TI  - Mathematical analysis of the chemosmotic polar diffusion of auxin through plant
      tissues.
AB  - Equations have been developed to describe the diffusional movement of a weak acid
      such as the auxin indoleacetic acid through a long file of vacuolated cells,
      where cellular accumulation is driven by the pH gradients across the cell
      membranes. If the permeability to the auxin anion is greater at one end of the
      cell than at the other, diffusional movement takes the form of polar transport,
      which exhibits: a nearly constant velocity either for the front or for a pulse of
      radioactive auxin, the capacity to move auxin against an external gradient of
      concentration, and a polar ratio that increases exponentially with the length of
      the section. The determinants of velocity include both diffusion through the
      vacuole and permeation steps at the cell membranes. Except for the permeabilities
      of the membranes to the anion, values are now available for all of the physical
      parameters in the equations. With reasonable estimates of permeability
      coefficients for the anion, the equations predict a velocity of transport of
      about 1 cm hr(-1), which agrees well with measured values. The analysis
      indicates, however, that the underlying cellular polarity may be greater than has
      been heretofore assumed. We thus demonstrate that the hypothesis of chemosmotic
      polar diffusion is capable of accounting quantitatively for the major features of
      auxin transport and provides a theoretical framework whose elements can be tested
      in future experiments.

PMID- 16592984
TI  - Photoaffinity labeling of an herbicide receptor protein in chloroplast membranes.
AB  - 2-Azido-4-ethylamino-6-isopropylamino-s-triazine (azido-atrazine) inhibits
      photosynthetic electron transport at a site identical to that affected by
      atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine). The latter is a
      well-characterized inhibitor of photosystem II reactions. Azido-atrazine was used
      as a photoaffinity label to identify the herbicide receptor protein; UV
      irradiation of chloroplast thylakoids in the presence of azido[(14)C]atrazine
      resulted in the covalent attachment of radioactive inhibitor to thylakoid
      membranes isolated from pea seedlings and from a triazine-susceptible biotype of
      the weed Amaranthus hybridus. No covalent binding of azido-atrazine was observed
      for thylakoid membranes isolated from a naturally occurring triazine-resistant
      biotype of A. hybridus. Analysis of thylakoid polypeptides from both the
      susceptible and resistant A. hybridus biotypes by sodium dodecyl
      sulfate/polyacrylamide gel electrophoresis, followed by fluorography to locate
      (14)C label, demonstrated specific association of the azido[(14)C]atrazine with
      polypeptides of the 34- to 32-kilodalton size class in susceptible but not in
      resistant membranes.

PMID- 16592985
TI  - Seismology and geodesy of the sun: Solar geodesy.
AB  - Measurements of the elliptical figure of the sun made in 1966 are analyzed on an
      hourly basis. This analysis yields an improved measure of the previously found
      solar distortion, rotating rigidly with a sidereal period of 12.38+/-0.10 days.
      It also yields a set of residuals used to search for signals due to low-frequency
      solar oscillations.

PMID- 16592986
TI  - Picosecond resonance Raman spectroscopic evidence for excited-state spin
      conversion in carbonmonoxy-hemoglobin photolysis.
AB  - The structure of the carbonmonoxy-hemoglobin (COHb) photoproduct has been studied
      on the picosecond time scale with resonance Raman spectroscopy, by tightly
      focusing the 30-ps pulses of a synchronously pumped mode-locked cavitydumped dye
      laser on a jet stream of COHb solution. The spectrum of the photoproduct is
      similar to that of deoxy Hb, but the frequencies 1603 cm(-1) (depolarized), 1552
      cm(-1) (anomalously polarized), and 1542 cm(-1) (depolarized) are 2-4 cm(-1)
      lower than those of deoxy Hb. Similar low frequencies are observed for a species
      believed to be the bis-tetrahydrofuran adduct of Fe(II) octaethylporphyrin,
      containing in-plane high-spin Fe(II). These results indicate that in the COHb
      photoproduct the Fe(II) is already high-spin but is closer to the heme plane than
      in deoxy Hb. Photodissociation from a quintet ligand-field excited state of COHb
      is suggested. The frequency shifts relative to deoxy Hb persist when the laser
      pulses are lengthened to 20 ns. The apparently slow relaxation to the fully out
      of-plane heme conformation of deoxy Hb is suggested to be associated with change
      of the globin tertiary structure.

PMID- 16592987
TI  - Alkyl-metal and aryl-metal bond chemistry in coordinately unsaturated polynuclear
      metal complexes.
AB  - A new class of coordinately unsaturated polynuclear rhodium and iridium alkyl,
      benzyl, and aryl derivatives of the form [RM(1,5-cyclooctadiene)](x) have been
      prepared by the reaction of the organolithium reagent with the
      cyclooctadienemetal chlorides at -78 degrees C. The x-ray crystal structure of
      [mu-CH(3)Rh (1,5-cyclooctadiene)](2) is reported. The analogous iridium dimer
      decomposes by an initial sequence of alpha-hydrogen abstraction and then
      reductive elimination of hydrogen to give [mu-CH(2)Ir(1,5-cyclooctadiene)](2).
      Formed in high yield by the decomposition of the ethylrhodium complex was
      [HRh(C(8)H(11))](4), a tetrahedral cluster with face-bridging hydride ligands.
      Also discussed are the reactivities of the benzyl and phenyl derivatives. Unique
      reaction pathways for C-H bond activation and scission in this chemistry are
      delineated.

PMID- 16592988
TI  - Hydrogenative deoxygenation of organic compounds: Direct conversion of amides to
      alkanes.
AB  - Through the use of (Cp(2)TiH)(x) or (Cp(2)Ti)(1-2), in which Cp is C(5)H(5)
      (cyclopentadienyl ligand), it is possible to effect not only the previously known
      direct reduction of aldehydes and esters to alkanes but also the one-step
      conversion to alkane of amides derived from selected primary aromatic amines.

PMID- 16592989
TI  - Circulant orbitals for atoms and molecules.
AB  - Circulant orbitals varphi(n) for a closed-shell system are the orbitals obtained
      when the N canonical orthonormal Hartree-Fock orbitals lambda([unk]) are
      subjected to a unitary transformation which is the discrete Fourier
      transformation: varphi(n) = 1/ radicalN Sigma([unk])lambda([unk])omega((n
      1)([unk]-1)), where omega = exp(2pii/N). Electron densities associated with the
      orbitals varphi(n) are each close to the average total electron density. The Fock
      matrix, diagonal for canonical orbitals, for circulant orbitals is a Hermitian
      circulant matrix, epsilon(m, m+q) = 1/N Sigma([unk])epsilon([unk])omega(q([unk]
      1)), where the epsilon([unk]) are the canonical orbital energies. The states
      ;Fvarphi(n) are uniformly distributed on the surface of a sphere in Hilbert
      space.

PMID- 16592990
TI  - Euler-Poisson equations on Lie algebras and the N-dimensional heavy rigid body.
AB  - The classical Euler-Poisson equations describing the motion of a heavy rigid body
      about a fixed point are generalized to arbitrary Lie algebras as Hamiltonian
      systems on coad-joint orbits of a tangent bundle Lie group. the N-dimensional
      Lagrange and symmetric heavy top are thereby shown to be completely integrable.

PMID- 16592991
TI  - Enumeration of structure-sensitive graphical subsets: Calculations.
AB  - Numerical calculations are presented, for all connected graphs on six and fewer
      vertices, of the numbers of independent sets, connected sets, point and line
      covers, externally stable sets, kernels, and irredundant sets. With the exception
      of the number of kernels, the numbers of such sets are all highly structure
      sensitive quantities.

PMID- 16592992
TI  - Accumulation of protoporphyrin IX and Zn protoporphyrin IX in Cyanidium
      caldarium.
AB  - In vivo fluorescence studies of Cyanidium caldarium mutants grown in the dark in
      dextrose-containing media have shown that these organisms accumulate
      protoporphyrin IX. In the dark the accumulated protoporphyrin IX is gradually
      turned into a metalloporphyrin, Zn protoporphyrin. In the light, in the
      chlorophyll-lacking mutant GGB, both compounds are degraded and phycobiliproteins
      are formed. These results implicate protoporphyrin IX in situ as the general
      precursor to tetrapyrrole pigments and Zn protoporphyrin IX as a possible
      intermediate or regulator in the biosynthesis of phycobilins.

PMID- 16592993
TI  - Metabolic stimulation by light in a pigmented freshwater invertebrate.
AB  - The pigmentation of terrestrial invertebrates has been shown to function in the
      optimization of solar warming, yet pigmented aquatic invertebrates have never
      been examined for the ability to utilize solar illumination in a similar manner.
      The degree of carotenoid pigmentation in calanoid copepods is easily quantified,
      and comparisons between populations suggest that variation in copepod
      pigmentation is related to variation in water temperature, with the most darkly
      pigmented copepods occurring in the coldest lakes. Darkly pigmented copepods show
      significantly higher metabolic rates in the light than in the dark, whereas
      lightly pigmented copepods do not. The metabolic experiments provide evidence
      that dark coloration is adaptive to cold-water copepods because it facilitates
      significant internal warming of tissues by sunlight. This hypothesis may be used
      to explain the pigmentation of many other cold-water invertebrates.

PMID- 16592994
TI  - Boundary-layer model for the population dynamics of single species.
AB  - We develop a new discrete-time model, called the boundary-layer model, to
      describe the dynamics of single species that have a capacity for fast growth at
      very low population densities. The model explicitly separates the dynamics of the
      population at very low densities (within the "boundary layer") and at high
      densities. The boundary-layer model provides a better fit than other models such
      as the logistic or the theta model to data from experimental populations of
      Drosophila willistoni and D. pseudoobscura.

PMID- 16592995
TI  - Enemy deterrence in the recruitment strategy of a termite: Soldier-organized
      foraging in Nasutitermes costalis.
AB  - The nasute soldiers of the neotropical termite Nasutitermes costalis function as
      scouts by exploring new terrain for food in advance of the worker caste and
      regulate foraging activity by laying trails composed of sternal gland pheromone.
      Additional soldiers are at first recruited in large numbers, and subsequently
      workers appear as the pheromone concentration increases. The role of the nasutes
      in the organization of foraging is extremely unusual for the soldier caste in
      social insects and appears to be a component of a foraging/defense system that
      controls the recruitment of foragers and effectively deters attacks by ants, the
      most fierce and important predators of termites.

PMID- 16592996
TI  - Large-scale flow generation in turbulent convection.
AB  - In a horizontal layer of fluid heated from below and cooled from above, cellular
      convection with horizontal length scale comparable to the layer depth occurs for
      small enough values of the Rayleigh number. As the Rayleigh number is increased,
      cellular flow disappears and is replaced by a random array of transient plumes.
      Upon further increase, these plumes drift in one direction near the bottom and in
      the opposite direction near the top of the layer with the axes of plumes tilted
      in such a way that horizontal momentum is transported upward via the Reynolds
      stress. With the onset of this large-scale flow, the largest scale of motion has
      increased from that comparable to the layer depth to a scale comparable to the
      layer width. The conditions for occurrence and determination of the direction of
      this large-scale circulation are described.

PMID- 16592997
TI  - Finite-time thermodynamics: Engine performance improved by optimized piston
      motion.
AB  - The methods of finite-time thermodynamics are used to find the optimal time path
      of an Otto cycle with friction and heat leakage. Optimality is defined by
      maximization of the work per cycle; the system is constrained to operate at a
      fixed frequency, so the maximum power is obtained. The result is an improvement
      of about 10% in the effectiveness (second-law efficiency) of a conventional near
      sinusoidal engine.

PMID- 16592998
TI  - Seismology and geodesy of the sun: Low-frequency oscillations.
AB  - The hourly averages of the solar ellipticity measured from June 13 to Sept. 17,
      1966, are analyzed for indications of solar oscillations with periods in excess
      of 2 hr nu < 0.5 hr(-1). Nothing significant is found for frequencies nu > 0.1
      hr(-1) but for lower frequencies the power spectrum shows a very complex
      structure containing about 20 strong narrow peaks. The complexity is illusionary.
      The signal apparently consists of only two frequencies. The complexity is due to
      aliasing by the window function with its basic 24-hr period, with many
      observational days missing, and with different numbers of hourly averages for the
      various observational days. Both signal frequencies are apparently due to odd
      degree spherical harmonic oscillations of the sun.

PMID- 16592999
TI  - Spectrophotometry of H II regions in the spiral galaxy M101.
AB  - Spectral line intensity data are presented for ionized hydrogen regions in the
      giant spiral galaxy M101. The influence of interstellar extinction is assessed
      and electron temperatures of the gas clouds are derived.

PMID- 16593000
TI  - C NMR chemical shift correlations in application of "tool of increasing electron
      demand" to stable long-lived carbocations: Comprehensive evaluation.
AB  - The reliability of (13)C NMR chemical shift correlations in the application of
      the "tool of increasing electron demand" to stable long-lived carbocationic
      systems is demonstrated by a comprehensive analysis of 22 stable aryl-substituted
      carbocationic systems. The observation of slopes of less than unity in such
      chemical shift correlations for several cationic systems has been attributed to
      additional charge delocalizing mechanisms present in the system (such as
      homoallylic, cyclopropyl, and pi conjugations). The onset of nonclassical sigma
      delocalization in 2-aryl-2-norbornyl cations with electron withdrawing
      substituents previously observed was further verified by using sigma(C+)
      substituent constants. Difficulties in relating the C(alpha)NMR shifts in
      different carbocationic systems are also discussed.

PMID- 16593001
TI  - On the density matrix approach of intramolecular relaxation processes.
AB  - In this paper we derive the generalized master equations for the S(1) system
      coupled with the S(2) system, with the S(1) and S(2) systems embedded in a heat
      bath. This formalism can be applied to a number of problems like vibrational
      redistribution, dynamic effect of vibrational relaxation on electronic relaxation
      in condensed media, etc. In this paper the importance of the memory function
      associated with a relaxation process is emphasized.

PMID- 16593002
TI  - Photosensitized electron transport across lipid vesicle walls: Enhancement of
      quantum yield by ionophores and transmembrane potentials.
AB  - The photosensitized reduction of heptylviologen in the bulk aqueous phase of
      phosphatidylcholine vesicles containing EDTA inside and a membrane-bound
      tris(2,2'-bipyridine)ruthenium(2+) derivative is enhanced by a factor of 6.5 by
      the addition of valinomycin in the presence of K(+). A 3-fold stimulation by
      gramicidin and carbonyl cyanide m-chlorophenylhydrazone is observed. The results
      suggest that, under these conditions, the rate of photoinduced electron transfer
      across vesicle walls in the absence of ion carriers is limited by cotransport of
      cations. The rate of electron transfer across vesicle walls could be influenced
      further by generating transmembrane potentials with K(+) gradients in the
      presence of valinomycin. When vesicles are made with transmembrane potentials,
      interior more negative, the quantum yield of heptylviologen reduction is doubled,
      and, conversely, when vesicles are made with transmembrane potentials, interior
      more positive, the quantum yield is decreased and approaches the value found in
      the absence of valinomycin.

PMID- 16593003
TI  - New reactions and theory in organic photochemistry: The 1,3-vinyl migration and
      its relevance to exchange integral control.
AB  - The photochemistry of 1,1,4-triphenyl-1,4-pentadiene was investigated. Sensitized
      irradiation of this compound labeled at carbon 3 with (2)H led to a degenerate
      rearrangement wherein the diphenylvinyl moiety migrated 1,3, thus affording diene
      with (2)H substitution at carbon 5. In contrast, direct irradiation of the
      triphenyl pentadiene led to 1,3,3-triphenylbicyclo[2.1.0]pentane by a [2 + 2]
      cycloaddition. This multiplicity dependence of the photochemistry is understood
      on the basis of triplet reactants preferring a linearly conjugated diradical
      mechanism with a large exchange integral (K) and singlet reactants preferring an
      electrocyclic mechanism with a small exchange integral.

PMID- 16593004
TI  - Method for constructing bijections for classical partition identities.
AB  - We sketch the construction of a bijection between the partitions of n with parts
      congruent to 1 or 4 (mod 5) and the partitions of n with parts differing by at
      least 2. This bijection is obtained by a cut-and-paste procedure that starts with
      a partition in one class and ends with a partition in the other class. The whole
      construction is a combination of a bijection discovered quite early by Schur and
      two bijections of our own. A basic principle concerning pairs of involutions
      provides the key for connecting all these bijections. It appears that our methods
      lead to an algorithm for constructing bijections for other identities of Rogers
      Ramanujan type such as the Gordon identities.

PMID- 16593005
TI  - Relaxation processes for a three-wave interaction model.
AB  - A system of waves coupled by three-wave, or triad, interactions is considered. A
      model is constructed to describe the response of a single test wave to
      interaction with a "heat bath" of "ambient waves." An exact solution for the
      relaxation of the test wave amplitude is obtained. Regimes of validity are shown
      for the use of a Langevin equation based on a two-time scale perturbation theory.

PMID- 16593006
TI  - Intercellular communication in plants: Evidence for a rapidly generated,
      bidirectionally transmitted wound signal.
AB  - Wounding (whether by excision, abrasion, or puncture) elicited rapid, massive,
      and enduring formation of polysomes in aged pea stems and other mature tissues.
      The response depended on temperature and severity of wounding but not on water
      uptake, and it occurred in tissues adjacent to, distant from, above, and below
      the site of injury. The kinetics of polysome formation were similar in tissues
      adjacent to or up to 150 mm distant from the point of injury. The wound-induced
      increases in protein-synthesizing capacity of the polysomes both in vivo and in
      vitro were much greater than the increases in rRNA and poly(A)(+)RNA. The results
      indicate that wounding evokes the almost immediate production of a wound signal
      that travels rapidly both acropetally and basipetally to stimulate the
      recruitment of preexisting ribosomes onto primarily preexisting mRNA, thence
      forming polysomes with greatly enhanced protein-synthesizing capacity.

PMID- 16593007
TI  - Breakage and propagation of the stony coral Acropora cervicornis.
AB  - Populations of the staghorn coral, Acropora cervicornis, often form dense
      monotypic stands on shallow Caribbean reefs. This coral species has a fragile
      structure that results in large numbers of broken branches and toppled colonies,
      especially in high wave activity. Although more than 80% of the corals in the
      studied population were broken from their bases, most had become reanchored to
      regrow rapidly. There is little evidence of sexual reproduction, and it appears
      that this coral has come to dominate much of the Jamaican reef community by
      propagation through fragmentation.

PMID- 16593008
TI  - Individual recognition and learning of queen odors by worker honeybees.
AB  - A honeybee queen is usually attacked if she is placed among the workers of a
      colony other than her own. This rejection occurs even if environmental sources of
      odor, such as food, water, and genetic origin of the workers, are kept constant
      in laboratory conditions. The genetic similarity of queens determines how similar
      their recognition characteristics are; inbred sister queens were accepted in 35%
      of exchanges, outbred sister queens in 12%, and nonsister queens in 0%. Carbon
      dioxide narcosis results in worker honeybees accepting nonnestmate queens. A
      learning curve is presented, showing the time after narcosis required by workers
      to learn to recognize a new queen. In contrast, worker transfers result in only a
      small percentage of the workers being rejected. The reason for the difference
      between queens and workers may be because of worker and queen recognition cues
      having different sources.

PMID- 16593009
TI  - Derivation of a formula for the resonance integral for a nonorthogonal basis set.
AB  - In a self-consistent field calculation, a formula for the off-diagonal matrix
      elements of the core Hamiltonian is derived for a nonorthogonal basis set by a
      polyatomic approach. A set of parameters is then introduced for the repulsion
      integral formula of Mataga-Nishimoto to fit the experimental data. The matrix
      elements computed for the nonorthogonal basis set in the pi-electron
      approximation are transformed to those for an orthogonal basis set by the Lowdin
      symmetrical orthogonalization.

PMID- 16593011
TI  - Multilayered iron complexes of [2.2]paracyclophane.
AB  - Recent syntheses of ruthenium complexes of [2.2]paracyclophane provided a highly
      interesting class of compounds, the multilayered transition metal complexes of
      cyclophanes. The present study discloses that arene-metal exchange procedures
      with ferrocene derivatives, effected either photochemically or by Lewis acid
      catalysis, are convenient methods for preparing the analogous multilayered iron
      complexes of [2.2]paracyclophane.

PMID- 16593010
TI  - pi cation radicals of ferrous and free base isobacteriochlorins: Models for
      siroheme and sirohydrochlorin.
AB  - Theoretical and experimental optical, redox, and paramagnetic results are
      presented for models of siroheme, the iron isobacteriochlorin prosthetic group of
      nitrite and sulfite reductases, and of sirohydrochlorin, the metal-free siroheme
      that is an intermediate in the biosynthetic pathway to vitamin B(12). The facile
      oxidation of many isobacteriochlorins, which distinguishes them from porphyrins
      and chlorins, suggests that the siroheme macrocycle itself may undergo oxidation
      in the multi-electron enzymatic cycles that reduce nitrite to ammonia and sulfite
      to hydrogen sulfide. Extended Huckel MO calculations (i) help rationalize the
      redox properties of isobacteriochlorins compared with those of porphyrins and
      chlorins; (ii) indicate that Fe(II) pyridine carbonyl[(py) (CO)] complexes of
      isobacteriochlorins, unlike those of porphyrins and chlorins, should undergo
      oxidation from the macrocycle rather than the metal to yield pi cation radicals;
      (iii) suggest that, in hexacoordinated Fe(II) isobacteriochlorin complexes, the
      site of oxidation-i.e., the metal or the macrocycle-will depend on the ligand
      field induced by the axial ligands; and (iv) predict similar unpaired spin
      density profiles for metal-free and (py) (CO)Fe(II) isobacteriochlorin radicals.
      Experimental data for three isomeric free-base and (py) (CO)Fe(II) complexes of
      dimethyloctaethylisobacteriochlorins support the theoretical calculations and
      establish the existence of Fe(II) isobacteriochlorin pi cations in vitro.

PMID- 16593012
TI  - Phase transition versus disorder: A criterion derived from a two-dimensional
      dynamic ferromagnetic model.
AB  - The dynamical equations for spin correlation functions for the two-dimensional
      Ising model are discussed for rapid-quench conditions. The temperature of the
      bath in which the Ising spins are immersed is postulated to be driven by the
      hyperbolic cooling program T(-1) = T(0) (-1) + bt (T(0) being the initial
      temperature, t the time, and b a constant). It is shown that for sufficiently
      large b the term in the dynamical equations that would normally drive the system
      into an ordered state would not have time to become effective so that the system
      freezes into a disordered state. The correlation length for the disordered state
      is characterized by the distance a random walker on a two-dimensional lattice
      would have been able to diffuse in the time required for the quench to reduce the
      temperature to some preassigned value.

PMID- 16593013
TI  - Proton transport in photooxidation of water: A new perspective on photosynthesis.
AB  - The currently prevalent concept of the generation of photosynthetic reducing
      power in oxygen-evolving cells envisions a linear (noncyclic) electron flow from
      water to ferredoxin (and thence to NADP(+)) that requires the collaboration of
      photosystems I and II (PSI and PSII) joined by plastoquinone and other electron
      carriers (the Z scheme). The essence of the Z scheme is that only PSI can reduce
      ferredoxin-i.e., that, after being energized to an intermediate reducing
      potential by PSII, electrons from water are transported via plastoquinone to PSI
      which energizes the electrons to their ultimate reducing potential adequate for
      the reduction of ferredoxin. Basic to the Z scheme is the function of
      plastoquinone as the obligatory link in electron transport from PSII to PSI.
      However, we have found that, when plastoquinone function was inhibited,
      ferredoxin was photoreduced by water without the collaboration of PSI. We now
      report evidence for an important function of plastoquinone in the translocation
      of protons liberated inside the thylakoid membrane by photooxidation of water.
      When the oxygenic photoreduction (i.e., by water) of ferredoxin was blocked by
      plastoquinone inhibitors, dibromothymoquinone or dinitrophenol ether of
      iodonitrothymol, the photoreduction of ferredoxin was restored by each of four
      chemically diverse uncouplers, similar only in their ability to facilitate proton
      movement across membranes. Similar results were obtained for the oxygenic
      reduction of NADP(+). Our results suggest that the light-induced electron flow
      from water cannot be maintained unless the simultaneously liberated protons are
      removed from inside the membrane via plastoquinone. The new evidence is embodied
      in a concept of an oxygenic photosystem for photosynthetic electron and proton
      transport, which we propose as an alternative to the Z scheme, to account for
      photoreduction of ferredoxin-NADP(+) by water and the coupled oxygenic (formerly
      noncyclic) ATP formation without involving PSI. The role of the anoxygenic
      photosystem (formerly called PSI) is ATP formation by cyclic
      photophosphorylation.

PMID- 16593014
TI  - Location of platinum binding sites on bacteriorhodopsin by electron diffraction.
AB  - A platinum-containing derivative of bacteriorhodopsin has been prepared by
      treating purple membranes with glycyl-L-methionatoplatinum. Low-dose electron
      diffraction was used to identify Pt binding sites in the 5.6 A resolution
      reconstruction of the bacteriorhodopsin unit cell in projection. This is a
      necessary first step in the use of the Pt derivative for identifying the parts of
      the amino acid sequence corresponding to the alpha helices in the
      bacteriorhodopsin structure and for obtaining phases for reflections out to 3.5 A
      resolution by the method of heavy-atom isomorphous replacement. The largest peak
      in a Fourier difference map between platinum-labeled and native purple membrane
      is larger than the spurious features expected to arise from errors in
      measurements of diffraction intensities.

PMID- 16593015
TI  - Monomeric chlorophyll a enol: Evidence for its possible role as the primary
      electron donor in photosystem I of plant photosynthesis.
AB  - The chlorophyll a (Chl a) special-pair model of the primary donor of photosystem
      I (P700) does not account in a completely adequate fashion for the magnetic
      resonance properties observed for P700(+). Moreover, P700 is at least 420 mV
      easier to oxidize than is Chl a in vitro. Neither Chl a dimer formation nor
      selective ligation of Chl a can account for this potential difference.
      Enolization of the Chl a ring V beta-keto ester results in a very different pi
      electronic structure. The Chl a enol can be trapped as a silyl enol ether. In
      addition, the enol analog 9-desoxo-9,10-dehydro-Chl a can be prepared. Both the
      trapped enol and its 9-H analog are approximately 350 mV easier to oxidize than
      Chl a. The ESR spectrum of the cation radical consists of a single 6.1-G gaussian
      line that is line narrowed relative to that of Chl a(+) in a manner similar to
      P700(+). Electron-nuclear double resonance (ENDOR) spectroscopy resolves only a
      3.5-MHz hyperfine splitting for the 3-methyl-group. The remaining splittings are
      all less than 3.5 MHz. The second moment of the ESR line of fully (13)C-enriched
      9-desoxo-9,10-dehydro-Chl a(+) agrees with that of [(13)C]P700(+) to within 10%.
      Application of the special-pair model to the [(13)C]P700(+) second-moment data
      yields a 100% error. Ab initio molecular orbital calculations on ethyl
      chlorophyllide a enol cation bear out the ESR and ENDOR data. We conclude that a
      monomeric Chl a enol model provides a better description of the magnetic
      resonance parameters and oxidation potential of P700 than a Chl a special-pair
      model.

PMID- 16593016
TI  - Probing the molecular structure of phytochrome with immobilized Cibacron blue 3GA
      and blue dextran.
AB  - Phytochrome was shown to bind to agarose-immobilized Cibacron blue 3GA. A higher
      affinity of the dye for the putative biologically active form (P(fr)) than the
      inactive form (P(r)) of phytochrome was observed. Effective general eluants of
      P(r) included 40% (vol/vol) ethylene glycol, 1% Triton X-100, or 0.5 M potassium
      iodide. Increasing ionic strength (1 M KCl) did not effectively elute
      phytochrome. Of the natural cofactors that have been reported to be analogues of
      the dye, NAD(+), NADH, NADP(+), cyclic AMP, AMP, ADP, ATP, and coenzyme A at a
      concentration of 10 mM would not elute phytochrome. At 10 mM, FMN eluted at least
      65% of the bound P(r), whereas FAD eluted 40%. Blue dextran/agarose was found to
      bind P(fr) but exhibited essentially no affinity for P(r). Phytochrome that was
      bound as P(fr) could be subsequently released by photoconversion to P(r). Because
      of the high degree of selectivity that the blue dye and its dextran conjugate
      exhibit for the P(fr) form of phytochrome and the known property of the dye as an
      analogue of natural ligands of proteins, it is proposed that the dye and its
      conjugate may be used as probes of a binding domain on the phytochrome protein
      that is important to its biochemical action.

PMID- 16593017
TI  - Apoplastic transport of ions in the motor organ of Samanea.
AB  - Turgor-mediated leaf movements of the legume Samanea saman are associated with
      the migration of K(+) and Cl(-) between opposing sides of the motor organs
      (pulvini). We have investigated the pathway of this ion migration by localizing
      K(+) and Cl(-) within the secondary pulvinus at various times during leaf
      movements. Ion distributions in freeze-dried cryosections of pulvini were
      determined by scanning electron microscopy/x-ray microanalysis. The results
      indicate that the apoplast is a major pathway for the migration of K(+) and Cl(-)
      within the pulvinus.

PMID- 16593018
TI  - Light limitation of photosynthesis and activation of ribulose bisphosphate
      carboxylase in wheat seedlings.
AB  - In limiting light the activation of ribulose-1,5-bisphosphate (RuP(2))
      carboxylase [3-phospho-D-glycerate carboxylyase (dimerizing), EC 4.1.1.39] in
      leaf extracts of 7- to 8-day-old wheat seedlings changed proportionally with the
      photosynthetic rate of the intact plants. Higher rates of photosynthesis, induced
      by increasing irradiances, were accompanied by an increase in activation of the
      leaf RuP(2) carboxylase, while RuP(2) levels remained unchanged. The degree of
      activation varied from 20% to 60% of full activation at irradiances of 225-1650
      muE/m(2).s (photosynthetically active radiation; E = einstein, 1 mol of photons).
      Between 225 muE/m(2).s and darkness, activation approached 50% while RuP(2)
      levels dropped more than 90%. During steady-state photosynthesis, levels of the
      substrate RuP(2) were 250-300 nmol/mg of chlorophyll in the leaves and were
      similar at all irradiances above 225 muE/m(2).s (25% of light saturation). When
      velocities of the carboxylase in leaf extracts were corrected for CO(2) levels
      estimated to exist within the leaf, they compared favorably with the
      photosynthetic rates of the intact seedlings. Comparison of CO(2) exchange rate,
      RuP(2) level, and activation of the carboxylase indicates that light limitation
      of photosynthesis can be due to two factors: the availability of RuP(2) in dark
      to dim light and activation of the RuP(2) carboxylase in dim light and higher
      irradiances.

PMID- 16593019
TI  - Full-grown oocytes from Xenopus laevis resume growth when placed in culture.
AB  - When most full-grown, follicle cell-invested oocytes from Xenopus laevis are
      placed in an appropriate culture medium, they resume growth and remain
      physiologically healthy for at least 2-3 weeks. Rates of growth by full-grown
      oocytes in vitro generally approximate and can even exceed the most rapid growth
      rate achieved by vitellogenic oocytes in vivo. Resumption of oocyte growth can be
      correlated with the loss of investing follicle cells, which under normal
      conditions appear to interfere with vitellogenin and nutrient access to the
      oocyte. The final size reached by the oocyte within the ovary is thus not an
      intrinsic property of the oocyte but is extrinsically imposed by the somatic
      environment.

PMID- 16593020
TI  - Regulation of synthesis of cell-specific ribosomal proteins during
      differentiation of Dictyostelium discoideum.
AB  - Proteins of ribosomes from various stages of development in Dictyostelium
      discoideum were analyzed by two-dimensional polyacrylamide gel electrophoresis.
      Significant changes in protein composition were observed; the data demonstrate
      that cell differentiation in a eukaryotic system is accompanied by ribosome
      heterogeneity. Both qualitative and quantitative differences were noted for 12
      unique ribosomal proteins between the vegetative amoebae and spores
      (differentiated cells). Two proteins were specific to ribosomes of amoebae, and
      three were specific to spores. The others were common to both cells but showed
      characteristic stoichiometric changes. The appearance and quantitative changes of
      these proteins were associated with specific stages of cell differentiation and
      were evident only during the aggregation phase; however, further changes
      continued through construction of fruiting bodies. As functional mRNAs for all 12
      proteins were present in both amoebae and spores, both transcriptional and
      translational mechanisms apparently regulate the synthesis of the various
      developmentally controlled ribosomal proteins in the two cell types.

PMID- 16593021
TI  - Sexual selection in Drosophila silvestris of Hawaii.
AB  - Previous discovery that Drosophila melanogaster females tend to discriminate in
      mating against phenotypes of earliest courting males prompted a study of the
      Hawaiian species D. silvestris. Tibial bristle variation in males from opposite
      coasts of the island of Hawaii functions in courtship, and the possibility that
      females can distinguish males differing in the tibial trait is explored. Mating
      tests, designed to give each female and male an alternative choice between two
      individuals of opposite sex every 30 min, consisted of intrapopulation tests with
      a strain derived from an eastern (Kilauea) population and interpopulation tests
      between that strain and one derived from a western (Kahuku) population. Males
      were given initial combat tests, with "winners" then used in mating (except one
      test with "loser" males). Matings (52-55%) were classified into categories
      according to the readiness of the female to mate and sequence of courtship. Low
      threshold females (accepting the first male after less than four courtship bouts)
      occurred at 30-35%. Among intrapopulational tests, females (with higher
      threshold) accepted first- and second-courting males about equally (25:36,
      respectively), but for male success in mating, the winning of initial intermale
      combats and the uniformity of courtship effort tended to be important criteria.
      Among interpopulation tests, homogamic matings were nearly equal (25% each), but
      heterogamic matings contrasted in that Kilauea females were reluctant to mate
      with Kahuku males (14%), while reciprocal matings occurred most frequently (34%).
      Females favored males second to court, particularly when a Kilauea male (with
      extra tibial bristles) was the second male. Thus a morphological feature likely
      to be influential in mating is demonstrated to be so; and sexual selection is
      operating via male-male combat plus discrimination in favor of particular
      opposite-sex individuals in this species.

PMID- 16593022
TI  - Analogues of red and white muscle in squid mantle.
AB  - In five species of squid, varying in life-style from fast-swimming pelagic
      predators to sluggish benthic forms, the circular muscle of the mantle was found
      to be metabolically and structurally differentiated into inner, middle, and outer
      zones. In the middle zone, mitochondrial abundance and the ratios of oxidative to
      glycolytic enzyme activities were low. This zone was sandwiched between thinner
      bands of muscle lining both the inner and outer edges of the mantle. In these
      bands, mitochondrial abundance and the ratios of oxidative to glycolytic enzyme
      activities were high. It is proposed that this metabolic differentiation is
      analogous to the development of red and white muscles in vertebrates and that it
      serves a similar function, white muscle mainly supporting burst-type swimming and
      red muscle sustaining steady-state oxidative work.

PMID- 16593023
TI  - Random walks with self-similar clusters.
AB  - We construct a random walk on a lattice having a hierarchy of self-similar
      clusters built into the distribution function of allowed jumps. The random walk
      is a discrete analog of a Levy flight and coincides with the Levy flight in the
      continum limit. The Fourier transform of the jump distribution function is the
      continuous nondifferentiable function of Weierstrass. We show that, for cluster
      formation, it is necessary that the mean-squared displacement per jump be
      infinite and that the random walk be transient. We interpret our random walk as
      having an effective dimension higher than the spatial dimension available to the
      walker. The difference in dimensions is related to the fractal (Hausdorff
      Besicovitch) dimension of the self-similar clusters.

PMID- 16593024
TI  - Lesion distribution, multiple infection, and the logistic increase of plant
      disease.
AB  - The lesions of few of the 112 observed cases of plant disease were randomly
      distributed; most were fitted by the negative binomial function with exponent
      approximately 1. The proportion of healthy hosts generally equaled the frequency
      of zero in the negative binomial. The same course of an epidemic is calculated
      for the logistic increase of infected plants or for plants infected by propagules
      produced in proportion to lesions and distributed with exponent equal 1.

PMID- 16593025
TI  - Nonlinear shear viscosity and long time tails.
AB  - A theoretical connection between nonlinear shear viscosity and the long time tail
      of the equilibrium stress-stress correlation function is pointed out. The
      connection is a consequence of the Goddard-Miller rheological equation of state
      which takes into account the angular rotation of a fluid in steady uniform shear.

PMID- 16593026
TI  - Nitration of naphthalene and remarks on the mechanism of electrophilic aromatic
      nitration.
AB  - Naphthalene was nitrated with a variety of nitrating agents. Comparison of data
      with Perrin's electrochemical nitration [Perrin, C. L. (1977) J. Am. Chem. Soc.
      99, 5516-5518] shows that nitration of naphthalene gives an alpha
      nitronaphthalene to beta-nitronaphthalene ratio that varies between 9 and 29 and
      is thus not constant. Perrin's data, therefore, are considered to be inconclusive
      evidence for the proposed one-electron transfer mechanism for the nitration of
      naphthalene and other reactive aromatics. Moodie and Schoefield [Hoggett, J. G.,
      Moodie, R. B., Penton, J. R. & Schoefield, K. (1971) Nitration and Aromatic
      Reactivity (Cambridge Univ. Press, London)], as well as Perrin, independently
      concluded that, in the general scheme of nitration of reactive aromatics, there
      is the necessity to introduce into the classical Ingold mechanism an additional
      step involving a distinct intermediate preceding the formation of the Wheland
      intermediate (sigma complexes). This view coincides with our two-step mechanistic
      picture [Kuhn, S. J. & Olah, G. A. (1961) J. Am. Chem. Soc. 83, 4564-4571] of the
      nitronium salt nitration of aromatic hydrocarbons (including benzene and
      toluene), in which low substrate selectivity but high positional selectivity was
      found, indicating the independence of substrate from positional selectivity.

PMID- 16593027
TI  - Enol-keto tautomerism of alpha-ketophosphonates.
AB  - A number of alpha-ketophosphonates have been prepared and their enol-keto
      tautomerism has been studied by means of proton and phosphorus NMR and infrared
      spectroscopy and the ferric chloride test. Aliphatic ketophosphonates exist
      largely in the keto tautomeric forms, with only a small amount of enol forms
      present. All the aromatic acylphosphonates studied, however, enolize extensively.
      An x-ray analysis confirmed enolization and E configuration as the only
      stereochemical isomer. Reaction of diazomethane with diethyl p
      methoxyphenylacetyl phosphonate gave a mixture of O-methylation and carbene
      insertion products, whereas the same reaction with diethyl isobutyryl phosphonate
      gave only carbene insertion products.

PMID- 16593028
TI  - Magnetic resonance spectroscopy of the primary state, P, of bacterial
      photosynthesis.
AB  - We have obtained the magnetic resonance spectrum of the radical pair state P(F)
      by using reaction yield detected magnetic resonance spectroscopy. The magnetic
      resonance spectrum is quite sensitive to the local environment of P(F). The data
      place limits on the lifetime of triplet P(F) and the distance of charge
      separation.

PMID- 16593029
TI  - Spin and wedge representations of infinite-dimensional Lie algebras and groups.
AB  - We suggest a purely algebraic construction of the spin representation of an
      infinite-dimensional orthogonal Lie algebra (sections 1 and 2) and a
      corresponding group (section 4). From this we deduce a construction of all level
      one highest-weight representations of orthogonal affine Lie algebras in terms of
      creation and annihilation operators on an infinite-dimensional Grassmann algebra
      (section 3). We also give a similar construction of the level-one representations
      of the general linear affine Lie algebra in an infinite-dimensional "wedge
      space." Along these lines we construct the corresponding representations of the
      universal central extension of the group SL(n)(k[t,t(-1)]) in spaces of sections
      of line bundles over infinite-dimensional homogeneous spaces (section 5).

PMID- 16593030
TI  - Overlapping divergent genes in the maize chloroplast chromosome and in vitro
      transcription of the gene for tRNA.
AB  - In the presence of the S polypeptide, maize chloroplast DNA-dependent RNA
      polymerase preferentially transcribes sequences within the 2200-nucleotide-pair
      long maize chloroplast chromosome fragment Eco [unk] from a supercoiled chimeric
      plasmid cloned in Escherichia coli [Jolly, S. O. & Bogorad, L. (1980) Proc. Natl.
      Acad. Sci. USA 77, 822-826]. Eco [unk] contains one gene for tRNA(His) and one
      for a 1.6-kilobase RNA that includes an open reading frame. These two genes
      overlap by at least a few nucleotides and are transcribed divergently from
      complementary DNA strands. This indicates possible transcriptional regulation of
      chloroplast DNA at the nucleotide level. The 5' end of tRNA(His) (G-U-G) isolated
      from maize chloroplasts is indistinguishable from that of the transcript produced
      from Eco [unk] in vitro by maize chloroplast DNA-dependent RNA polymerase. This
      purified system initiates RNA synthesis faithfully and exhibits preference for
      some chloroplast genes. Maize chloroplast DNA for tRNA(His) lacks the sequence C
      C-A at its 3' terminus; it is presumably added post-transcriptionally. Maize
      tRNA(His) has both prokaryotic and eukaryotic features.

PMID- 16593031
TI  - Cloning, mapping, and in vitro transcription-translation of the gene for the
      large subunit of ribulose-1,5-bisphosphate carboxylase from spinach chloroplasts.
AB  - An 11.2-kilobase pair (kbp) BamHI restriction nuclease fragment from spinach
      chloroplast DNA has been found to contain the gene for the large subunit (LS) of
      ribulose-1,5-bisphosphate carboxylase [RuP(2) carboxylase; 3-phospho-D-glycerate
      carboxy-lyase (dimerizing), EC 4.1.1.39]. The gene was located by hybridization
      of cloned chloroplast DNA fragments containing the maize LS gene (Bedbrook, J.
      R., Coen, D. M., Beaton, A. R., Bogorad, L. & Rich, A. (1979) J. Biol. Chem. 254,
      905-910) to spinach chloroplast DNA cleaved with restriction nucleases. The 11.2
      kbp BamHI fragment has been inserted into the BamHI site of the plasmid pBR322.
      The resulting recombinant plasmid, pSoe3101, was used to direct the synthesis of
      a protein, which was immunoprecipitable with antibody to RuP(2) carboxylase, in a
      partially defined in vitro transcription-translation system derived from
      Escherichia coli. The product synthesized in vitro has a molecular weight
      identical to that of authentic spinach LS. By using pSoe3101 DNA cleaved at
      various positions with restriction nucleases, and the in vitro transcription
      translation system, the LS gene has been mapped to a 1.5-kbp region located at
      one end of the 11.2-kbp BamHI fragment. The direction of transcription of the LS
      gene on the plasmid as well as on the chloroplast chromosome has also been
      determined. The position of the LS gene on circular spinach chloroplast DNA is
      approximately 27 kbp from the start of one of the inverted repeat regions and 180
      degrees from one of the rRNA-coding regions.

PMID- 16593032
TI  - Heat shock proteins of higher plants.
AB  - The pattern of protein synthesis changes rapidly and dramatically when the growth
      temperature of soybean seedling tissue is increased from 28 degrees C (normal) to
      about 40 degrees C (heat shock). The synthesis of normal proteins is greatly
      decreased and a new set of proteins, "heat shock proteins," is induced. The heat
      shock proteins of soybean consist of 10 new bands on one-dimensional NaDodSO(4)
      gels; a more complex pattern is observed on two-dimensional gels. When the tissue
      is returned to 28 degrees C after 4 hr at 40 degrees C, there is progressive
      decline in the synthesis of heat shock proteins and reappearance of a normal
      pattern of synthesis by 3 or 4 hr. In vitro translation of poly(A)(+)RNAs
      isolated from tissues grown at 28 and 40 degrees C shows that the heat shock
      proteins are translated from a new set of mRNAs induced at 40 degrees C;
      furthermore, the abundant class mRNAs for many of the normal proteins persist
      even though they are translated weakly (or not at all) in vivo at 40 or 42.5
      degrees C. The heat shock response in soybean appears similar to the much-studied
      heat shock phenomenon in Drosophila.

PMID- 16593033
TI  - Proteinase inhibitor-inducing factor activity in tomato leaves resides in
      oligosaccharides enzymically released from cell walls.
AB  - The synthesis and accumulation of proteinase inhibitor I in excised tomato leaves
      can be induced with oligosaccharides obtained by fungal endo-alpha-1,4
      polygalacturonase digestion of a pectic polysaccharide (M(r) 5000-10,000)
      isolated from tomato leaves. Active oligosaccharides were also released from
      isolated tomato leaf cell walls by endopolygalacturonases partially purified from
      tomato plants. It is suggested that oligosaccharides, released from plant cell
      wall pectic polysaccharides by either endogenous or exogenous
      endopolygalacturonases at a wound or infection site, may have hormone-like roles
      in regulating plant defense responses in unwounded tissues many centimeters away
      from the site of release.

PMID- 16593034
TI  - Separation and characterization of inner and outer envelope membranes of pea
      chloroplasts.
AB  - A procedure for purifying the chloroplast envelope subfractionates it into two
      membrane fractions of comparable quantities. This procedure differs from previous
      ones in that the chloroplasts are ruptured by freezing and thawing in hypertonic
      medium rather than by osmotic shock. The two membrane fractions have
      qualitatively similar polar lipid compositions but differ in their content of
      individual lipids, specifically monogalactosyldiacylglycerol and
      phosphatidylcholine. The two fractions also differ in their constituent
      polypeptides and in their appearance when examined by electron microscopy. The
      light (density = 1.08 g/ml) and heavy (density = 1.13 g/ml) membrane fractions
      have been tentatively identified as the outer and inner envelope membranes,
      respectively.

PMID- 16593035
TI  - Embryonic proteins in somatic embryos of carrot.
AB  - The translational profile of cultured carrot cells (callus) was compared with
      that of the somatic embryos derived from them. The two tissues synthesize almost
      the same number and kinds of polypeptides except for two "embryonic" proteins.
      These were found in the somatic embryos but were nearly undetectable in the
      callus. Both embryo development and the production of embryonic proteins were
      induced by the same trigger (transfer of the callus to fresh medium) and were
      suppressed by the same factor (2,4-dichlorophenoxyacetic acid). But the
      appearance and disappearance of the proteins occurred several days prior to
      embryo formation and to the conversion of embryo to callus, respectively. Carrot
      cell lines incapable of embryogenesis could not synthesize the embryonic
      proteins. These findings indicate that the embryonic proteins play a key role in
      the process of embryo development. The function of these proteins is presently
      unknown; however, they can serve as early developmental markers for studying the
      mechanisms underlying somatic embryogeny in plants.

PMID- 16593036
TI  - Models of speciation by sexual selection on polygenic traits.
AB  - The joint evolution of female mating preferences and secondary sexual characters
      of males is modeled for polygamous species in which males provide only genetic
      material to the next generation and females have many potential mates to choose
      among. Despite stabilizing natural selection on males, various types of mating
      preferences may create a runaway process in which the outcome of phenotypic
      evolution depends critically on the genetic variation parameters and initial
      conditions of a population. Even in the absence of genetic instability, rapid
      evolution can result from an interaction of natural and sexual selection with
      random genetic drift along lines of equilibria. The models elucidate genetic
      mechanisms that can initiate or contribute to rapid speciation by sexual
      isolation and divergence of secondary sexual characters.

PMID- 16593037
TI  - Gene number in species of Astereae that have different chromosome numbers.
AB  - Differences in the gametic chromosome numbers (n = 4, 5, 9) of species in the
      Astereae tribe of the Compositae have been variously interpreted. One hypothesis
      proposes that n = 9 was the original base number of the group and that the lower
      numbers resulted from aneuploid reduction. The alternative hypothesis asserts
      that the ancestral base number was n = 4 or n = 5 and that species in which n = 9
      are allotetraploids derived by hybridization between taxa with the lower numbers.
      Electrophoretic analysis of 17 enzyme systems in five species of Machaeranthera,
      in which n = 4, 5, and 9, and two species of Aster in which n = 5 and 9,
      demonstrates that all of these species have the same number of gene loci
      specifying the tested enzymes. The absence of isozyme multiplicity in the species
      in which n = 9 suggests that they did not arise by polyploidy.

PMID- 16593038
TI  - Preferential mating in symmetric multilocus systems.
AB  - A class of multilocus models that incorporate both preferential mating and
      viability selection is studied. Symmetry in alleles is supposed, resulting in the
      phenotypes being dependent only on the location of heterozygous loci. Otherwise,
      an arbitrary number of loci, number of alleles per locus, and arbitrary
      recombination schemes, viability parameters, and preferential mating pattern are
      allowed. The conditions for stability of a central polymorphism, c(*), are
      indicated and interpreted. Mating and viability parameters enter as one combined
      quantity for each phenotypic class, which represents a generalized fitness. The
      effect on stability of c(*) of increasing the number of alleles per locus and the
      number of loci requires the formulation to be set in terms of frequency-dependent
      preference parameters.

PMID- 16593039
TI  - Impaired induction and self-catabolite repression of extracellular pectate lyase
      in Erwinia chrysanthemi mutants deficient in oligogalacturonide lyase.
AB  - The pectate lyase (PL; EC 4.2.2.2) secreted by the plant pathogen Erwinia
      chrysanthemi is induced and catabolite repressed by different concentrations of
      its own product, digalacturonic acid 4,5-unsaturated at the nonreducing end
      [u(GalUA)(2)]. Both activities of u(GalUA)(2) depend on its cleavage by
      oligogalacturonide lyase (OGL; EC 4.2.2.6). This intracellular enzyme converts
      u(GalUA)(2) to the deoxyketuronic acid 4-deoxy-L-threo-5-hexosulose uronic acid,
      which is then isomerized to 3-deoxy-D-glycero-2,5-hexodiulosonic acid. An OGL
      deficient mutant unable to grow on u(GalUA)(2) was poorly induced by u(GalUA)(2)
      or by D-galacturonan but produced wild-type levels of PL when supplied with 3
      deoxy-D-glycero-2,5-hexodiulosonic acid. PL synthesis in the mutant could also be
      stimulated by 4,5-unsaturated trigalacturonic acid, from which deoxyketuronic
      acid is released by another intracellular enzyme. An OGL-deficient mutant that
      grew slowly on u(GalUA)(2) in comparison with the wild-type parent was
      hyperinduced by u(GalUA)(2) unless catabolite repression was relieved by cyclic
      AMP or imposed by logarithmic growth on glycerol. PL synthesis is also stimulated
      by saturated digalacturonic acid, which is released from D-galacturonan by
      another extracellular enzyme, exo-poly-alpha-D-galacturonosidase (EC 3.2.1.82).
      Because these dimers stimulate PL synthesis at concentrations (wt/vol) 1/1000th
      of the concentration required by D-galacturonan, and because an OGL-deficient
      mutant uninducible by dimers was also uninducible by D-galacturonan, we postulate
      that PL induction by pectic polymers entails extracellular formation of dimers
      and subsequent intracellular conversion to deoxyketuronic acids, the apparent
      inducers of PL.

PMID- 16593040
TI  - Lumsden-Wilson theory of gene-culture coevolution.
AB  - A critique is presented of the Lumsden-Wilson theory [Lumsden, C. J. & Wilson, E.
      O. (1980) Proc. Natl. Acad. Sci. USA 77, 4382-4386] of the transmission of
      cultural traits. An analysis of the underlying assumptions and the mathematical
      nature of the theory clarifies its essentially reductionist and determinist
      qualities. The mathematical functions governing the transition probability that
      an individual member of a group of a specified size will switch from one trait to
      an alternative form of that trait is assumed to be genetically controlled
      although the single independent variable of this function, the number of
      individuals characterized by each of the two forms of the trait, is
      environmentally determined. The model assumes that the cultural properties of a
      society are simply the sum of the properties of the individuals; that each
      individual is equally influenced by every other member of the group; and that
      kinship structures, cultural institutions, and historical factors can be
      neglected.

PMID- 16593041
TI  - Metal-hydrogen bridge bonding of hydrocarbons on metal surfaces.
AB  - Molecular orbital studies implicate multicenter metal-hydrogen-carbon
      interactions as contributors to the bonding of chemisorbed hydrocarbons on clean
      metal surfaces. The most stable geometries appear to be those that achieve the
      maximum multicenter bonding to the coordinately unsaturated metal atoms in the
      vicinity of the anchoring metal-carbon interaction. Energy differences between
      possible surface sites are of the same magnitude as stabilization energies for
      three-center bonding of hydrogen atoms to the metal surface. Accordingly,
      secondary interactions of hydrogen with neighboring metal atoms may be
      significant determining factors in surface structures. The model predictions are
      compared with known structures and are used to propose a mechanism for
      hydrocarbon reactions on metal surfaces. These metal-hydrogen-carbon interactions
      are presumed to be intermediate points or states in C-H bond-breaking processes.

PMID- 16593042
TI  - Syntheses of all singly labeled [N]adenines: Mass spectral fragmentation of
      adenine.
AB  - Syntheses of all five of the singly labeled [(15)N]adenines are now provided. The
      presence or absence of two-bond (15)N-(1)H spin couplings in their (1)H NMR
      spectra confirm the location of the isotope in each case. The fragmentation
      patterns in their mass spectra are indicative of the sequential losses of HCN
      units and of CH(2)N(2) from adenine upon electron impact.

PMID- 16593043
TI  - Quantum statistical mechanical theory of diffusion and reaction on solid
      surfaces.
AB  - We present the derivation of the general kinetic equations of diffusion and
      diffusion with interaction (or chemical reaction) on solid surfaces (or in dense
      media) by using the density matrix method. We indicate several problems to which
      this formalism applies and, in particular, discuss the damping effect on
      diffusion.

PMID- 16593044
TI  - Sharp local bounds for orders of contact.
AB  - I outline a proof of the sharp local bound for a jump discontinuity in the
      maximum order of contact of complex analytic varieties with a real hypersurface.
      This involves a new algebraic-geometric approach to questions arising in the
      study of the Cauchy-Riemann equations.

PMID- 16593045
TI  - All binomial identities are verifiable.
AB  - Sister Celine Fasenmyer's technique for obtaining pure recurrence relations for
      hypergeometric polynomials is formalized and used to show that every identity
      involving sums of products of binomial coefficients can be verified by checking a
      finite number of its special cases.

PMID- 16593046
TI  - On irregularities of distribution of real sequences.
AB  - A natural measure of the amount of unavoidable clustering that must occur in any
      bounded infinite sequence of real numbers is studied. We determine the extreme
      value for this measure and exhibit sequences that achieve this value.

PMID- 16593047
TI  - Semiclassical model for atoms.
AB  - The energies of several two- and three-electron atoms, in both ground states and
      excited states, are calculated by a very simple semiclassical model. The only
      change from Bohr's original method is to replace definite orbits by probability
      distribution functions based on classical dynamics. The energies are better than
      Hartree-Fock values. There is still a need for an exchange-energy correction.

PMID- 16593048
TI  - Molecular parameters and olfaction in the oriental fruit fly Dacus dorsalis.
AB  - The methyl eugenol receptor of the male oriental fruit fly (Dacus dorsalis) has
      been further characterized by evaluating the role of the linear free energy
      parameters product operator and sigma in the depolarization of the receptor by 37
      substituted 3,4-dimethoxybenzenes. There was a strong positive correlation
      between the hydrophobic character of the primary substituent and intense odor and
      a positive correlation between the electron donating property of the primary
      substituent and intense odor. Maximum odor intensity was also associated with
      substituents of 3 atomic diameters and was improved by a center of unsaturation.
      Preference tests suggest that this simple and versatile odor receptor can serve
      as a model for investigation of molecular interactions between receptors and
      odorant molecules.

PMID- 16593049
TI  - On the attribution and additivity of binding energies.
AB  - It can be useful to describe the Gibbs free energy changes for the binding to a
      protein of a molecule, A-B, and of its component parts, A and B, in terms of the
      "intrinsic binding energies" of A and B, DeltaG(A) (i) and DeltaG(B) (i), and a
      "connection Gibbs energy," DeltaG(s) that is derived largely from changes in
      translational and rotational entropy. This empirical approach avoids the
      difficult or insoluble problem of interpreting observed DeltaH and TDeltaS values
      for aqueous solutions. The DeltaG(i) and DeltaG(s) terms can be large for binding
      to enzymes and other proteins.

PMID- 16593050
TI  - Isolation and characterization of virus-specific double-stranded DNA from tissues
      infected by bean golden mosaic virus.
AB  - A double-stranded (ds) DNA which may be a replication intermediate was isolated
      from bean (Phaseolus vulgaris L. "Top Crop") leaves systemically infected with
      bean golden mosaic virus, a whitefly-transmitted plant virus with a genome of
      circular single-stranded (ss) DNA. The isolation method used phenol/chloroform
      extraction, hydroxyapatite column chromatography, and rate-zonal centrifugation.
      The dsDNA had sequences complementary to those of viral DNA. The guanine-plus
      cytosine content was 35%, and the sedimentation coefficient in alkaline sucrose
      density gradients was similar to that of viral ssDNA. Digestion of the dsDNA by
      Hha I endonuclease produced fragments that corresponded exactly in number and
      size with those produced by complete digestion of circular viral ssDNA by Hha I,
      when the fragments were denatured and analyzed on polyacrylamide gels. The dsDNA
      molecule was a circular structure with one discontinuity in one strand;
      hybridization results suggest that some of a the dsDNA has a discontinuity in the
      viral strand and some has a discontinuity in the nonviral strand. On the basis of
      these structures for the dsDNA, a preliminary model for replication of viral DNA
      is discussed.

PMID- 16593051
TI  - Ageing of alpha-chymotrypsin: Cannibalistic and hydroxide ion reactions.
AB  - The loss of catalytic activity (irreversible denaturation) of alpha-chymotrypsin
      (EC 3.4.21.1) as a function of pH between 6 and 13 is described. Around
      neutrality the irreversible denaturation is second order with respect to enzyme.
      At high pH, the irreversible denaturation is first order with respect to enzyme
      and also with respect to hydroxide ion. The first- or second-order dependency on
      enzyme concentration has been shown both by the time course of denaturation and
      by the effect of enzyme concentration on the rate of denaturation. The first
      order dependency on hydroxide ion was shown by a plot of the logarithm of the
      rate constant vs. pH. These enzyme inactivations are peptide bond cleavages at
      all pH values. From the kinetics, the irreversible denaturation can be described
      as a cannibalistic reaction of two enzyme molecules around neutrality or as a
      reaction of one enzyme molecule plus one hydroxide ion at high pH.

PMID- 16593052
TI  - Elimination of cannibalistic denaturation by enzyme immobilization or inhibition.
AB  - The cannibalistic denaturation of alpha-chymotrypsin (EC 3.4.21.1) around neutral
      pH can be eliminated by immobilization (insolubilization) of the enzyme or by
      inhibition by specific reversible inhibitors, but the high-pH denaturation cannot
      be. The denaturation of the immobilized enzyme at high pH follows first-order
      kinetics, just as the denaturation of the soluble enzyme does. These results lend
      credence to the description of the denaturation of chymotrypsin as cannibalistic
      around neutrality and due to a hydroxide ion reaction at high pH; this
      interpretation followed from kinetic arguments given in the previous article [Wu,
      H.-L., Wastell, A. & Bender, M. L. (1981) Proc. Natl. Acad. Sci. USA 78, 4116
      4117]. Elimination of denaturation around neutrality by immobilization may be the
      reason why membrane-bound enzymes are so common in vivo.

PMID- 16593053
TI  - Multiple conformations at functional site of hemerythrin: Evidence from resonance
      Raman spectra.
AB  - Resonance Raman spectra were obtained for monomeric oxymyohemerythrin and for the
      azide, thiocyanate, cyanate, cyanide, and fluoride adducts of metmyohemerythrin.
      The internal ligand vibrations in these complexes appear at essentially the same
      frequencies as those in the corresponding complexes of octameric hemerythrin.
      Likewise the Fe-O frequencies in H(2) (16)O do not depend on quaternary structure
      of the protein. The anionic adducts fall into two classes in regard to isotope
      exchange behavior in H(2) (18)O. They also manifest a novel photochemical
      transformation from one class of exchange behavior to the other. It seems evident
      that the functional site in hemerythrin exists in at least two different
      conformational states and that irradiation can stimulate isotope exchange in the
      exchange-resistant form.

PMID- 16593054
TI  - Relative orientation of close-packed beta-pleated sheets in proteins.
AB  - When beta-pleated sheets pack face to face in proteins, the angle between the
      strand directions of the two beta-sheets is observed to be near -30 degrees . We
      propose a simple model for beta-sheet-to-beta-sheet packing in concanavalin A,
      plastocyanin, gamma-crystallin, superoxide dismutase, prealbumin, and the
      immunoglobin fragment V(REI). This model shows how the observed relative
      orientation of two packed beta-sheets is a consequence of (i) the rows of side
      chains at the interface being approximately aligned and (ii) the beta-sheet
      having a right-handed twist. The special amino acid composition of residues at
      the beta-sheet-to-beta-sheet interfaces makes the contact surfaces essentially
      smooth and hydrophobic.

PMID- 16593055
TI  - Revertant seedlings from crown gall tumors retain a portion of the bacterial Ti
      plasmid DNA sequences.
AB  - BT37 is a crown gall teratoma incited on tobacco by Agrobacterium tumefaciens
      containing pTi-T37, a nopaline-type Ti plasmid. Treatment of this cloned tumor
      tissue with kinetin at 1 mg/liter results in the formation of relatively normal
      appearing shoots. These shoots can be induced to root and set viable seed. In
      contrast to BT37 tissue, the derived tissues are not phytohormone independent and
      do not produce nopaline. The reverted plants, like normal tobacco plants, are
      susceptible to infection by A. tumefaciens. This loss of tumorous traits is
      accompanied by the loss of most of the Ti plasmid sequences (T-DNA) found in BT37
      DNA. Southern blot analysis indicates that the revertant tissues have lost the
      central portion of the T-DNA, which contains the "common DNA" sequences, a highly
      conserved region of the Ti plasmid that has been found to be incorporated into
      all tumors studied. Thus, these sequences appear necessary for oncogenicity and
      tumor maintenance and their loss is probably directly related to tumor reversal.
      The reverted plants as well as the plants obtained from seed, however, do retain
      sequences homologous to the ends of the T-DNA present in the parental teratoma.
      The persistence of foreign DNA sequences during the process of meiosis and seed
      formation has important implications for the possibility of the genetic
      engineering of plants.

PMID- 16593056
TI  - X-ray analysis (1. 4-A resolution) of avian pancreatic polypeptide: Small
      globular protein hormone.
AB  - The crystal structure of avian pancreatic polypeptide (aPP), a 36-residue
      polypeptide with some hormonal properties, has been determined by using single
      isomorphous replacement and anomalous scattering to 2.1-A resolution. The phases
      were extended to 1.4-A resolution by using a modified tangent formula. The
      molecule contains two regions of secondary structure-an extended polyproline-like
      helix (residues 1-8) and an alpha-helix (residues 14-31)-that run roughly
      antiparallel. The packing together of nonpolar groups from these regions gives
      the molecule a hydrophobic core in spite of its small size. The aPP molecules
      form a symmetrical dimer in the crystal stabilized principally by interlocking of
      nonpolar groups from the alpha-helices. The aPP dimers are crosslinked by
      coordination of Zn(2+); three aPP molecules contribute ligands to each zinc. The
      coordination geometry is a distorted trigonal bipyramid. The properties of the
      aPP molecule in solution are consistent with expectations based on the crystal
      structure. The aPP molecule has several general features in common with the
      pancreatic hormones insulin and glucagon. All three hormones have complex
      mechanisms for self-association. Like insulin, aPP seems to have a stable
      monomeric structure but its biological activity seems to depend on the more
      flexible COOH-terminal region analogous to the flexible NH(2)-terminal region of
      glucagon.

PMID- 16593057
TI  - Correlation between particle multiplicity and location on virion RNA of the
      assembly initiation site for viruses of the tobacco mosaic virus group.
AB  - The initiation site for reconstitution on genome RNA was determined by electron
      microscopic serology for a watermelon strain of cucumber green mottle mosaic
      virus (CGMMV-W), which is chemically and serologically related to tobacco mosaic
      virus (TMV). The initiation site was located at the same position as that of the
      cowpea strain, a virus that produces short rods of encapsidated subgenomic
      messenger RNA for the coat protein (a two-component TMV), being about 320
      nucleotides away from the 3' terminus, and hence within the coat protein cistron.
      Although CGMMV-W was until now believed to be a single-component TMV, the
      location of the initiation site indicated the presence of short rods containing
      coat protein messenger RNA in CGMMV-W-infected tissue, as in the case for the
      cowpea strain. We found such short rods in CGMMV-W-infected tissue. The results
      confirmed our previous hypothesis that the site of the initiation region for
      reconstitution determines the rod multiplicity of TMV. The finding of the second
      two-component TMV, CGMMV, indicates that the cowpea strain of TMV is not unique
      in being a two-component virus and that the location of the assembly initiation
      site on the genome RNA can be a criterion for grouping of viruses.

PMID- 16593058
TI  - C(4)-dicarboxylate transport mutants of Rhizobium trifolii form ineffective
      nodules on Trifolium repens.
AB  - Mutants of Rhizobium trifolii strain 7012 defective in C(4)-dicarboxylate
      transport were isolated by using a selective procedure based on pH indicator
      media. The mutant strains CR7098 and CR7099 failed to grow on or transport
      succinate, fumarate, or malate, but grew at wild-type rates on several other
      carbon sources. The C(4)-dicarboxylate transport system was inducible in strain
      7012, but was expressed constitutively in four out of five succinate-positive
      revertants of strain CR7098. In the fifth CR7098 revertant (strain CR8008) the
      system was inducible. However, in contrast to strain 7012, strain CR8008 failed
      to use the C(4)-dicarboxylates in the presence of a second carbon source.
      Revertants of strain CR7099 were similar to strain 7012. Both strains CR7098 and
      CR7099 nodulated white and red clover at a rate similar to that of strain 7012,
      but nodules formed by the mutant strains were white and ineffective. Microscopic
      examination showed that the pattern of development of white clover nodules formed
      by strain CR7098 was similar to that observed with nodules formed by strain 7012,
      except that large amounts of starch accumulated in bacteroid-filled cells and
      senescence occurred earlier. Revertant strains were effective, except for strain
      CR8008, which formed ineffective nodules. The results show that a supply of C(4)
      dicarboxylates to bacteroids is essential for nitrogen fixation in clover
      nodules. However, rhizobia within plant cells must also utilize other carbon
      sources to support growth and division.

PMID- 16593059
TI  - Differential expression of crown gall tumor markers in transformants obtained
      after in vitro Agrobacterium tumefaciens-induced transformation of cell wall
      regenerating protoplasts derived from Nicotiana tabacum.
AB  - To obtain transformation of plant cells, we incubated 3-day-old cell wall
      regenerating protoplasts from tobacco with Agrobacterium tumefaciens harboring
      tumor-inducing plasmids. Putative transformed tobacco cells were selected by
      phytohormone autotrophic growth and were shown to be transformed by the detection
      of the tumor cell specific enzymes lysopine dehydrogenase or nopaline
      dehydrogenase. This was substantiated by the detection, in transformed tumor
      tissues, of DNA sequences homologous to sequences in the tumor-inducing plasmid.
      Segregation of tumor markers has been observed among the transformants and it is
      suggested that this happened during the initiation of the transformation. The
      stable character of the transformed state was shown by the retention of tumor
      markers in subcloning of primary transformants under nonselective conditions.
      Suppression of the neoplastic state of transformants could take place, resulting
      in the development of transformed shoots. Indications were obtained for the
      inheritance of tumor markers through meiosis from seedlings obtained from seeds
      of flowering transformed plants that still expressed nopaline synthesis.

PMID- 16593060
TI  - Larval selectivity for yeast species by Drosophila mojavensis in natural
      substrates.
AB  - The yeast flora found in the major substrates of Drosophila mojavensis and in
      larval guts was studied both qualitatively and quantitatively. Quantitative
      studies show that, in four of the five substrates tested, the larvae did not
      contain a random sample of the yeasts present in the substrates. One widely
      distributed cactus yeast, Pichia cactophila, was typically in greater frequency
      in the larvae than in the substrates. Another cactus yeast, Candida sonorensis,
      typically exhibited the opposite relationship. Laboratory tests support larval
      preference behavior rather than differential digestion as being primarily
      responsible. Larvae are capable of distinguishing between patches of different
      yeast species and spend more time in patches of preferred yeasts. D. mojavensis
      appear to be ecological (host plants) generalists and physiological (yeasts)
      specialists in contrast to the other cactophilic Drosophila. Selective feeding by
      D. mojavensis larvae in natural substrates may represent optimal foraging
      behavior.

PMID- 16593061
TI  - Genes, individuals, and kin selection.
AB  - The altruistic-gene theory of kin selection requires conditions so improbable
      that its reality is doubtful. The gene-quantity theory, including the theory of
      inclusive fitness, assumes that selection acts on sums of kins' genes, but no
      effective mechanism is apparent. Insect and human societies may have evolved by
      individual selection, in two steps: first something made staying together
      advantageous to individuals, and then altruistic behaviors evolved in net-gain
      lotteries, also (statistically) advantageous to individuals. Kin selection is not
      required in these or any other unequivocal cases; the theory should be reexamined
      and probably abandoned. The probability of kin selection is further reduced by
      the cost of evolution by selection. Much current evolutionary mathematics and
      determinist sociobiology, which ignore how the cost of selection limits the
      precision of adaptations, including adaptive behaviors, may be dangerously
      unrealistic.

PMID- 16593062
TI  - Sequence homology among different size classes of plant mtDNAs.
AB  - Supercoiled mtDNAs were isolated from tissue culture cells of tobacco, bean, and
      corn, and the smallest size classes were used to study the relationships among
      the different size classes of each species through restriction digests and
      hybridizations. Three of the smallest tobacco mtDNAs [10.1, 20.2, and 28.8
      kilobases (kb)], the two smallest bean mtDNAs (1.9 and 3.8 kb), and the two
      smallest corn mtDNAs (1.5 and 1.8 kb) were extracted from the gels and nick
      translated. The 10.1-kb tobacco mtDNA hybridizes to all the other tobacco mtDNA
      size classes and a large percentage of the tobacco mtRNAs. Restriction digests
      indicate that the 20.2-kb size class is a dimer of the 10.1-kb size class. The
      1.9-kb bean mtDNA hybridizes to all but three of the bean mtDNA size classes and
      hybridizes to two mtRNAs. Restriction digests indicate that the 3.8-kb size class
      is a dimer of the 1.9-kb size class. The 1.5- and 1.8-kb corn mtDNAs, which do
      not have any Hha I restriction fragments in common, both hybridize to many of the
      same size classes of the corn mtDNA profile and, in addition, each hybridizes to
      a few size classes not recognized by the other. The 1.5- and 1.8-kb size classes
      both hybridize to two RNAs, one of which they appear to have in common. However,
      with both the 1.9-kb bean mtDNA and the two corn mtDNAs, the molecular sizes of
      the two RNAs exceed those of the respective DNAs. The possible role and origin of
      the many size classes are discussed.

PMID- 16593063
TI  - Highly repeated DNA sequence limited to knob heterochromatin in maize.
AB  - A highly repeated DNA sequence has been isolated from the maize genome as a
      satellite in actinomycin D/CsCl gradients. By using maize stocks differing in
      their heterochromatin content we have established that the sequence is a major
      constituent of one class of heterochromatin, knob heterochromatin, which can
      occur at 23 locations in the chromosome complement. The repeating unit, of 185
      base pairs, has been cloned in plasmid pBR322 and its nucleotide sequence has
      been determined. The presence of this DNA sequence in knob heterochromatin and
      its absence from centromeric, nucleolar, and B chromosome heterochromatin
      parallels the cytogenetic differentiation previously described for these classes
      of heterochromatin in maize. Because knob heterochromatin has a distinctive
      cytological appearance and is unique in showing neocentric activity at meiosis,
      its association with a particular repeated DNA sequence may reflect a functional
      role for the sequence in the cell cycle.

PMID- 16593064
TI  - Gut bacteria recycle uric acid nitrogen in termites: A strategy for nutrient
      conservation.
AB  - Reticulitermes flavipes termites synthesize uric acid via purine-nucleoside
      phosphorylase (purine-nucleoside: orthophosphate ribosyltransferase, EC 2.4.2.1)
      and xanthine dehydrogenase (xanthine:NAD(+) oxidoreductase, EC 1.2.1.37), but
      their tissues lack uricase (urate:oxygen oxidoreductase, EC 1.7.3.3) or any other
      enzyme that degrades uric acid. Nevertheless, uricolysis occurs in termites, but
      as an anaerobic process mediated by hindgut bacteria. (14)C-Tracer experiments
      showed that termites transport uric acid from the site of synthesis and storage
      (fat body tissue) to the site of degradation (hindgut microbiota) via Malpighian
      tubules. Moveover, [1,3-(15)N]uric acid dissimilated by gut bacteria in vivo
      leads to assimilation of (15)N into termite tissues. NH(3), a product of
      uricolysis, is a potential N source for termites, either directly via glutamine
      synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] activity of fat
      body tissue or indirectly through microbe assimilation. Symbiotic recycling of
      uric acid N appears to be important to N conservation in these oligonitrotrophic
      insects.

PMID- 16593065
TI  - Heterogeneous platinum-catalyzed hydrogenation of dialkyl(diolefin)platinum(II)
      complexes: A new route to platinum surface alkyls.
AB  - Platinum metal catalyzes the reduction of dialkyl(diolefin)platinum(II) complexes
      by dihydrogen to alkanes and platinum(0). The reaction involves adsorption of the
      platinum(II) complex on the platinum(0) catalyst surface with conversion of the
      alkyl moieties to platinum surface alkyls; these appear as alkane products. The
      platinum atom originally present in the soluble organoplatinum species becomes
      part of the platinum(0) surface.

PMID- 16593066
TI  - Phanerozoic cycles of sedimentary carbon and sulfur.
AB  - A reservoir model of a Recent steady-state sedimentary system in which the
      reduced sulfur and oxidized sulfur reservoirs were coupled with the oxidized
      carbon and reduced carbon reservoirs was constructed. The time curve of the
      sulfur isotope ratios of the sedimentary sulfate reservoir was used to drive the
      model back to the beginning of Cambrian time (600 million years ago), producing
      the reservoir sizes and isotope values and material fluxes of the carbon-sulfur
      system. The predicted values of carbon isotope ratios of the carbonate reservoir
      agree well with observed values, showing that the model is basically sound. Some
      general conclusions from this success are (i) material flux rates in the carbon
      oxygen-sulfur system of the geologic past (averaged over tens of millions of
      years) lie within about a factor of 2 of Recent rates. (ii) The oxidation
      reduction balances of Phanerozoic time were dominated by reciprocal relationships
      between carbon and sulfur compounds. (iii) The rate of production of atmospheric
      oxygen by storage in sediments of organic carbon of photosynthetic origin
      increased from the Cambrian Period to the Permian Period and declined somewhat
      from the Permian Period to the Present. (iv) The storage of oxygen in oxidized
      sulfur compounds kept pace (within the limits of the data) with oxygen
      production. (v) Transfer of oxygen from CO(2) to SO(4) from the Cambrian to the
      Permian Period was several times the Recent free oxygen content of the
      atmosphere.

PMID- 16593067
TI  - Some isometric embedding and rigidity results for Riemannian manifolds.
AB  - In this note, we announce some new results concerning rigidity and isometric
      embeddings of Riemannian manifolds. A special case of the main result states that
      a general M(n) [unk] R(n+r), r</=(n - 1)(n - 2)/2, is uniquely determined up to
      finitely many constants by its induced ds(2).

PMID- 16593068
TI  - Rubel's universal differential equation.
AB  - Fourth-order differential equations such as 16y'(m)y'(2) - 32y(m)y(n)y' +
      17y(0(3) ) = 0 are developed. It is shown that the equation is "universal" in the
      sense that any continuous function can be approximated with arbitrary accuracy
      over the whole x axis by a solution y(x) of the equation. This solution is a
      piecewise polynomial of degree 9 and of class C(4).

PMID- 16593069
TI  - Selecting the highest probability in binomial or multinomial trials.
AB  - Some sequential procedures are considered for selecting the binomial population
      with largest success probability or for selecting the multinomial outcome with
      highest cell probability. Procedures with and without sequential elimination of
      inferior populations are evaluated with respect to the expected probability of
      the population selected.

PMID- 16593070
TI  - Structure of the body-centered cubic phase of lipid systems does not consist of
      indefinitely long straight rods.
AB  - The observed intensities of the reflections from the body-centered cubic phase of
      lipid systems are shown to be incompatible with a recently reported model
      consisting of straight, indefinitely long rods.

PMID- 16593071
TI  - A gene coding for tRNA is located near 5' terminus of 16S rRNA gene in Zea mays
      chloroplast genome.
AB  - A region of 635 base pairs preceding a gene for 16S rRNA in the Zea mays
      chloroplast genome has been mapped and its sequence has been determined.
      Screening for structural elements common to tRNAs reveals a gene coding for
      tRNA(Val) (GU(U) (C)) positioned 303 base pairs proximal to the 5' end of the 16S
      rRNA gene. Both the tRNA(Val) and the 16S rRNA are coded in the same DNA strand.
      The tRNA nucleotide sequence predicted from the DNA sequence meets all structural
      characteristics common to tRNA primary and secondary structures. In a
      quantitative comparison with primary structures of the 14 known tRNA(Val) species
      the chloroplast isoaceptor shows much higher homology with that from prokaryotic
      than that from eukaryotic species. Regions that Escherichia coli RNA polymerase
      protects from nuclease attack are observed 25 and 100 base pairs upstream of the
      tRNA(Val) gene and 105 base pairs upstream of the 16S rRNA gene. Within these
      regions are short sequences that are very similar to those in the -35 region of
      E. coli rrn and that may therefore represent all or parts of transcription
      initiation signals of the respective genes.

PMID- 16593072
TI  - Are viroids escaped introns?
AB  - A complex of considerable stability is possible between the 5' end of U1 RNA and
      a specific nucleotide sequence of the potato spindle tuber viroid complement.
      Because base-pairing between the 5' end of U1 RNA and the ends of introns is
      believed by some to be responsible for the precise alignment and correct excision
      of introns, the U1-related sequence may represent the two ends of a presumed
      intron ancestor of the viroid complement after circularization.

PMID- 16593073
TI  - Niche packing and coevolution in competition communities.
AB  - A coevolutionary model of species packing is developed that allows evolutionary
      adjustment in both niche position and within-phenotype niche width of one-three
      competing species. The environment is specified as a single resource dimension x
      and availability of resources along x is given by a gaussian curve that has
      parameters x[unk](R) and sigma(R). The model predicts that, for S species, the
      ratio of optimal niche width w[unk] to sigma(R) is roughly independent of
      sigma(R) and can be approximated by 1/S when the competitors are completely
      resource limited. Niche separation (d[unk]/w[unk]) increases only moderately with
      increases in resource diversity sigma(R) and is greater for two than for three
      competing species. To the extent that the competitors are not completely resource
      limited, both coevolutionary niche separation and niche width decrease. Many of
      the general trends in niche width and niche separation predicted by this
      coevolutionary model parallel those from optimal foraging theory and limiting
      similarity models of community structure. The coevolutionary model stands out,
      however, in the singularly high values predicted for niche separation, making
      coevolved communities highly invasible. Hence, the theory suggests, as some
      empirical evidence indicates, that coevolved competition communities can only
      eixst as such on remote islands or in other habitats that might be free from
      invasion by outside species.

PMID- 16593074
TI  - Population genetic theory of kin selection: Multiple alleles at one locus.
AB  - Exact population genetic models of one-locus sib-to-sib kin selection with an
      arbitrary number of alleles are studied. First, a natural additive scaling is
      established for the genotypic value associated with probabilities of performance
      of altruism. Two classes of polymorphic equilibria are possible, one
      corresponding to the usual one-locus viability equilibria and the other
      reflecting the kin-selection assumptions of the model. At both, the covariance
      between additive genotypic value and genotypic fitness vanish. Further, the sign
      of this covariance determines the fate of rare alleles introduced near the first
      class of equilibria. In addition, the covariance explains the differences between
      Hamilton's rule, which results from Hardy-Weinberg assumptions, and exact initial
      increase conditions.

PMID- 16593076
TI  - Chemical composition of high-excitation planetaries.
AB  - Nebular spectral line intensities measured mostly in the optical region, but also
      in the IR and satellite UV (where possible), are used to derive plasma
      diagnostics and ionic concentrations n (X(i))/n(H(+)). Then, we use theoretical
      nebular models to represent as closely as possible certain excitation-sensitive
      line ratios of HeII/HeI, [OIII]/[OII], and [NeIII]/[NeV]. Also, we try to
      reproduce the line intensities themselves. These models are used as devices to
      allow for unobserved ionization stages. Although He, C, and N show significant
      variations among different nebulae, heavier elements such as O, and probably Ne,
      S, Cl, and Ar are more nearly constant, suggesting that progenitor stars
      underwent nuclear transformations in their interiors that affected C and N but
      not heavier elements.

PMID- 16593075
TI  - Covariant chronogeometry and extreme distances: Elementary particles.
AB  - We study a variant of elementary particle theory in which Minkowski space, M(0),
      is replaced by a natural alternative, the unique four-dimensional manifold M with
      comparable properties of causality and symmetry. Free particles are considered to
      be associated (i) with positive-energy representations in bundles of prescribed
      spin over M of the group of causality-preserving transformations on M (or its
      mass-conserving subgroup) and (ii) with corresponding wave equations. In this
      study these bundles, representations, and equations are detailed, and some of
      their basic features are developed in the cases of spins 0 and (1/2).
      Preliminaries to a general study are included; issues of covariance, unitarity,
      and positivity of the energy are treated; appropriate quantum numbers are
      indicated; and possible physical applications are discussed.

PMID- 16593077
TI  - Periodicity in the isotope chemistry of hydrogen.
AB  - Periodicities and regularities are established among the deuterium to protium
      isotopic reduced partition function ratios, ln(s/s')f, of 39 diatomic and 19
      polyatomic hydrides. It is shown that ln(s/s')f for diatomic hydrides can be
      correlated with the position in the periodic table of the element X in the
      hydride HX. A similar analysis is made for the contributions from X-H stretching
      motion in the polyatomic hydrides H(n)X. It is shown that the contributions from
      stretching motions to ln(s/s')f in diatomic and polyatomic molecules are a linear
      function of the square root of the stretching force constants. The contributions
      from bending coordinates to ln(s/s')f depend on both the molecular structure of
      the hydride and the bending force constant. Simple correlations are established
      for the bending contributions to ln(s/s')f for the hydrides of the elements
      belonging to a common group in the periodic table. Four periodic rules of the
      isotope chemistry of hydrogen summarize and classify the data on the isotopic
      partition function ratios and the isotopic differences in free energies of
      formation of hydrides.

PMID- 16593078
TI  - Molecular engineering: An approach to the development of general capabilities for
      molecular manipulation.
AB  - Development of the ability to design protein molecules will open a path to the
      fabrication of devices to complex atomic specifications, thus sidestepping
      obstacles facing conventional microtechnology. This path will involve
      construction of molecular machinery able to position reactive groups to atomic
      precision. It could lead to great advances in computational devices and in the
      ability to manipulate biological materials. The existence of this path has
      implications for the present.

PMID- 16593079
TI  - Impact of upwardly revised DeltaH(f) of primary, secondary, and tertiary radicals
      on mechanistic constructs in thermal reorganizations.
AB  - Impetus for upward revision in the heats of formation of the ethyl (primary),
      isopropyl (secondary), and t-butyl (tertiary) free radicals has gained sufficient
      momentum in the last 6 yr to prompt an illustrative assessment of the far-ranging
      implications for interpretation of thermal reorganizations. Previous obstacles to
      consideration of diradicals as transition states in rearrangements of
      cyclopropanes and cyclobutanes are removed. The energetic relation of cyclohexa
      1,4-diyl as an intermediate diradical in the Cope rearrangement to the transition
      state of a concerted mechanism is clarified.

PMID- 16593080
TI  - Model of clustering of earthquakes.
AB  - A two-dimensional model of the expansion of a crack in an elastic medium is
      considered in which friction depends on the slip rate and the modulus of cohesion
      depends on the speed of expansion of the crack. Elastic waves are neglected
      (quasi-static model). Under some conditions, the expansion of the crack is
      realized by the alternation of slow and fast episodes ("shocks") of slip. This
      offers a possible qualitative explanation of several forms of earthquake
      clustering, including clustering that is premonitory to strong earthquakes.

PMID- 16593081
TI  - Representation of weakly harmonizable processes.
AB  - Weakly harmonizable processes are represented by a family of positive definite
      contractive linear operators in a Hilbert space. This generalizes the known
      result on weakly stationary processes involving a unitary family. A
      characterization of the vector Fourier integral of a measure on R --> [unk], a
      reflexive space, is given, and this yields another characterization of weakly
      harmonizable processes when [unk] is a Hilbert space. Also these processes are
      shown to have associated spectra, yielding a positive solution to a problem of
      Rozanov.

PMID- 16593082
TI  - The hard-hexagon model and Rogers-Ramanujan type identities.
AB  - In regime II of Baxter's solution of the hard-hexagon model [Baxter, R. J. (1980)
      J. Phys. A 13, L61-L70], he presents six conjectures identifying certain one
      dimensional partition functions with infinite products. An outline of the proof
      of these conjectures is given here.

PMID- 16593083
TI  - Fourier-transform analysis of normal photoelectron diffraction data for surface
      structure determination.
AB  - A direct method for surface-structure determination from normal emission
      photoelectron diffraction (NPD) data is presented. Fourier transforms of the
      calculated NPD intensities yield peaks at adsorbate-substrate normal interlayer
      distances. Applications are demonstrated, using theoretical NPD curves for the
      Se/Ni system calculated by dynamical theory. These results show that interplanar
      spacings between the overlayer and as many as four substrate layers can be
      determined with an accuracy of better than 3%.

PMID- 16593084
TI  - Changes in the structure of nuclei between the magic neutron numbers 50 and 82 as
      indicated by a rotating-cluster analysis of the energy values of the first 2
      excited states of isotopes of cadmium, tin, and tellurium.
AB  - Values of R, the radius of rotation of the rotating cluster, are calculated from
      the observed values of the energy of the lowest 2(+) states of the even isotopes
      of (48)Cd, (50)Sn, and (52)Te with the assumption that the cluster is alpha,
      p(2), and alpha, respectively. R shows a maximum at approximately N = 58, a
      minimum at approximately N = 62, and a second maximum at approximately N = 70.
      The increase to the first maximum is interpreted as resulting from the
      overcrowding of spherons (alphas and tritons) in the mantle (outer layer) of the
      nuclei, causing the cluster to change from rotating in the mantle to skimming
      over its surface; the decrease to the minimum results from the addition of three
      dineutrons to the core, expanding the mantle and permitting the rotating cluster
      to begin to drop back into it; and the increase to the second maximum results
      from the overcrowding of the larger mantle surrounding the core containing the
      semi-magic number 14 of neutrons rather than the magic number 8 for N = 50. The
      decrease after the second maximum results from the further increase in the number
      of core neutrons to 20, corresponding to the magic number 82. Some additional
      evidence for the change to an intermediate structure between N = 50 and N = 82 is
      also discussed.

PMID- 16593085
TI  - Glitches and pinned vorticity in the Crab pulsar.
AB  - We suggest that the glitch behavior observed in the Crab pulsar is associated
      with vorticity jumps induced by a starquake or a comparable external fluctuation
      in the weakly pinned vortex region expected in the crust of a young neutron star,
      and that the differences in the glitch behavior of the Crab, Vela, and older
      pulsars may be explained on evolutionary grounds.

PMID- 16593086
TI  - Structure of a chromosomal gene for human interferon beta.
AB  - We have cloned and analyzed a chromosomal DNA segment containing the human
      interferon beta(1) gene from a human gene library. The nucleotide sequence of the
      protein-coding and the noncoding regions of the chromosomal gene was identical to
      the cDNA sequence reported previously. In the region upstream from the putative
      transcription initiation site, significant nucleotide sequence homology was
      observed between interferon beta(1) and alpha(1) genes. This region thus may play
      a role in expression of the interferon genes. From the sequence data and the
      result of nuclease S1 mapping experiments, we conclude that, like the interferon
      alpha(1) gene, the interferon beta(1) gene is devoid of intervening sequences.

PMID- 16593087
TI  - Rearrangements in the chloroplast genomes of mung bean and pea.
AB  - We have mapped all the cleavage sites for the restriction endonucleases BstEII,
      Kpn I, Pst I, Pvu II, Sac I, Sal I, Sma I, and Xho I on the circular chloroplast
      chromosomes from mung bean and pea. The mung bean chloroplast genome measures 150
      kilobase pairs (kb) in length; it includes two identical sequences of 23 kb that
      contain the ribosomal genes and are arranged as an inverted repeat separated by
      single-copy regions of 21 and 83 kb. The pea chloroplast genome is only 120 kb in
      size, has only one set of ribosomal genes, and does not possess any detectable
      repeated sequences. The mung bean inverted repeat structure is common to all
      other nonleguminous higher plant chloroplast genomes studied, whereas the pea
      structure has been found only in the closely related legume Vicia faba. We
      conclude from these data that loss of one copy of the inverted repeat sequence
      has occurred only rarely during the evolution of the Angiosperms, and in the case
      of the legumes after the divergence of the mung bean line from the pea-Vicia
      line. We present hybridization data indicating that rearrangements that change
      the linear order of homologous sequences within the chloroplast genome have been
      quite frequent during the course of legume evolution.

PMID- 16593088
TI  - Electrostatic control of the efficiency of light-induced electron transfer across
      membranes.
AB  - The energetics and efficiency of light-induced electron transfer across membranes
      is examined on a molecular level. It is found that the activation energies that
      control the efficiency are determined by the solvation energies of the charge
      transfer states, the redox potentials of the donors and acceptors, and the
      dielectric relaxation of the system. The formalism developed allows one to assess
      the efficiency of any artificial photosynthetic system in terms of its molecular
      components and their local environment. It is pointed out that the key problem in
      designing an efficient photosynthetic system is the transfer of a charge through
      a low dielectric environment and that this problem cannot be overcome by choosing
      the position of the primary donor and acceptor in the membrane. It is predicted
      that artificial photosynthetic systems can be optimized by placing the acceptors
      in polar sites that provide a large effective dielectric constant and low
      dielectric relaxation and by arranging the acceptors in order of increasing redox
      potentials. The implication regarding bacterial photosynthesis is discussed.

PMID- 16593089
TI  - Mg/KCl-ATPase of plant plasma membranes is an electrogenic pump.
AB  - The function of the Mg(2+)-requiring KCl-stimulated ATPase (ATP phosphohydrolase,
      EC 3.6.1.3) of higher plants in active ion transport was investigated by using a
      purified microsomal fraction containing sealed plasma membrane vesicles. (Sze, H.
      (1980) Proc. Natl. Acad. Sci. USA 77, 5904-5908). A transmembrane electrical
      potential (+30 to +44 mV), monitored by uptake of a permeant anion ((35)SCN(-)),
      was generated specifically by ATP in purified microsomal vesicles of tobacco
      callus. ATP-dependent (35)SCN(-) uptake required Mg(2+), was optimal at pH 6.75,
      and showed similar ATP concentration dependence as the Mg(2+)-requiring KCl
      stimulated ATPase activity. Plasma membrane ATPase inhibitors (N,N'
      dicyclohexylcarbodiimide and vanadate) inhibited generation of the ATP-dependent
      electrical potential. A proton conductor (carbonyl cyanide m
      chlorophenylhydrazone), but not a K(+) ionophore (valinomycin), completely
      collapsed the electrical potential. The results provide in vitro evidence that
      the Mg(2+)/KCl-ATPase of higher plants is an electrogenic pump. These results are
      consistent with the hypothesis that an electrogenic H(+) pump is catalyzed by the
      plasma membrane ATPase of plants.

PMID- 16593090
TI  - B850 pigment-protein complex of Rhodopseudomonas sphaeroides: Extinction
      coefficients, circular dichroism, and the reversible binding of
      bacteriochlorophyll.
AB  - Chromatophores of Rhodopseudomonas sphaeroides yield the antenna complex B850 in
      either of two states, depending on the method of isolation. Methods using dodecyl
      (= lauryl) dimethylamine oxide yield B850 with an absorption spectrum like that
      in vivo: the bands at 800 and 850 nm, due to the bacteriochlorophyll (Bchl)
      components Bchl-800 and Bchl-850, are in ratio A(800)/A(850) = 0.65 +/- 0.05.
      When B850 is isolated by methods using dodecyl sulfate, the Bchl-800 is
      attenuated or absent. Bchl assays of these materials and of the isolated antenna
      complex B875 yielded the following extinction coefficients, +/-SD, on the basis
      of the molarity of Bchl: For B875, epsilon(875) = 126 +/- 8 mM(-1) cm(-1). For
      B850 in the normal (high-Bchl-800) state, epsilon(850) = 132 +/- 10 mM(-1) cm(
      1). For the individual components of Bchl in B850, epsilon(850) of Bchl-850 = 184
      +/- 13 mM(-1) cm(-1) and epsilon(800) of Bchl-800 = 213 +/- 28 mM(-1) cm(-1).
      With these coefficients the molecular ratio of Bchl-850 to Bchl-800 equals 1.8 +/
      0.4 for B850 in the high-Bchl-800 state. Starting with B850 depleted of Bchl
      800, the addition of dodecyldimethylamine oxide restored the 800-nm absorption
      band. The 850-nm band became shifted toward the blue, narrowed, and slightly
      attenuated, and its associated circular dichroism became 20% more intense. Free
      Bchl added with dodecyldimethylamine oxide accelerated the restoration of Bchl
      800 and retarded the attenuation of Bchl-850. We conclude that free Bchl can
      interact reversibly with a binding site for Bchl-800 in the B850 complex, with
      dodecyl sulfate favoring dissociation and dodecyldimethylamine oxide promoting
      association. Thus the reversible dissociation of a native chlorophyll-protein
      complex has now been demonstrated.

PMID- 16593091
TI  - Spontaneous and evoked release of prothoracicotropin from multiple neurohemal
      organs of the tobacco hornworm.
AB  - Release of neurohormone from putative cephalic neurohemal organs was directly
      demonstrated in an insect. The prothoracicotropic hormone (PTTH) of the tobacco
      hornworm, Manduca sexta, was measured indirectly by its ability to stimulate the
      secretion of alpha-ecdysone by inactive prothoracic glands; the ecdysone was
      measured by radioimmunoassay. The PTTH released spontaneously from intact brain
      retrocerebral complexes was localized to the retrocerebral complex by placing a
      waxy barrier across the nerves connecting the corpora cardiaca to the brain.
      Isolated corpora allata spontaneously released much more PTTH than did either
      isolated corpora cardiaca or isolated brains. Media containing 100 mM potassium
      stimulated PTTH release from both isolated corpora allata and isolated corpora
      cardiaca. In calcium-free media, spontaneous PTTH release was diminished and
      release could not be stimulated by high potassium. These results indicate that
      depolarization of the neurosecretory cells is correlated with calcium-dependent
      neurohormone release and that there are multiple neurohemal organs for PTTH. The
      biological activities of stored and circulating PTTH are compared.

PMID- 16593092
TI  - Population structure of multilocus associations.
AB  - A method of analysis is presented whereby the structure of multilocus
      associations among and within several populations can be partitioned into its
      components. The components are measured by their contributions to the variance in
      the number of heterozygous loci in two randomly chosen gametes. The singlelocus
      components are the average and the variation among populations in gene diversity
      and the variance among populations in allele frequency. The two-locus components
      include the mean and variance of disequilibria, the covariance of allele
      frequencies over populations, and various interactions. When applied to allozyme
      data from populations of wild (Hordeum spontaneum) and cultivated barley (H.
      vulgare), the analysis highlighted the repetitive pattern of the multilocus
      associations in the composite crosses whereas it emphasized the regionally
      localized and geographically variable pattern present in the natural populations
      of the wild species. The analysis is flexible and applicable to multilocus
      gametic data from any set of populations, without regard to the number of alleles
      per locus or the reproductive method of the organism.

PMID- 16593094
TI  - General quantitative treatment for the binding of divalent antibodies to antigens
      immobilized on a solid phase.
AB  - A general expression for the binding isotherm of divalent antibodies to antigens
      bound to solid lattices with excluded volume effects is derived by using a
      statistical mechanical approach. The method is based on matrix generation of the
      partition function for the system, from which the degree of saturation of the
      antigen lattice may be computed directly. The saturation function has a simple
      form that under appropriate conditions reduces to forms derived previously for
      simpler cases (such as monovalent binding with and without excluded volume
      effects). Solution by numerical techniques of a simple secular equation for each
      concentration of antibody allows computation of the saturation function. Thus,
      the binding expression derived is easily fit to any set of binding data obtained
      and results in the determination of such parameters as intrinsic affinity
      constants, length of excluded space (and hence molecular size), and number of
      sites. It predicts that under conditions wherein divalent binding is favored over
      univalent binding, biphasic adsorption isotherms will be obtained.

PMID- 16593095
TI  - Photosensitized electron transfer processes in SiO(2) colloids and sodium lauryl
      sulfate micellar systems: Correlation of quantum yields with interfacial surface
      potentials.
AB  - The effectiveness of negatively charged colloidal SiO(2) particles in controlling
      photosensitized electron transfer reactions has been studied and compared with
      that of the negatively charged sodium lauryl sulfate (NaLauSO(4)) micellar
      system. In particular, the photosensitized reduction of the zwitterionic electron
      acceptor propylviologen sulfonate (PVS(0)) with tris(2,2'
      bipyridinium)ruthenium(II) [Ru(bipy)(3) (2+)] as the sensitizer and
      triethanolamine as the electron donor is found to have a quantum yield of 0.033
      for formation of the radical anion (PVS([unk])) in the SiO(2) colloid compared
      with 0.005 in the homogeneous system and 0.0086 in a NaLauSO(4) micellar
      solution. The higher quantum yields obtained with the SiO(2) colloidal system are
      attributed to substantial stabilization against back reaction of the intermediate
      photoproducts-i.e., Ru(bipy)(3) (3+) and PVS([unk])-by electrostatic repulsion of
      the reduced electron acceptor from the negatively charged particle surface. The
      binding properties of the SiO(2) particles and NaLauSO(4) micelles were
      investigated by flow dialysis. The results show that the sensitizer binds to both
      interfaces and that the SiO(2) interface is characterized by a much higher
      surface potential than the micellar interface ( approximately -170 mV vs. -85
      mV). The effect of ionic strength on the surface potential was estimated from the
      Gouy-Chapman theory, and the measured quantum yields of photosensitized electron
      transfer were correlated with surface potential at different ionic strengths.
      This correlation shows that the quantum yield is not affected by surface
      potentials smaller than approximately -40 mV. At larger potentials, the quantum
      yield increases rapidly. The quantum yield obtained in the micellar system at
      different strengths fits nicely on the correlation curve for the colloid SiO(2)
      system. These results indicate that the surface potential is the dominant factor
      in the quantum yield improvement for PVS(0) reduction.

PMID- 16593093
TI  - Steric control of CO binding in a totally synthetic heme protein model.
AB  - A family of totally synthetic models for the carbon monoxide adducts of heme
      proteins has been synthesized and applied to the elucidation of the role of
      steric effects in the relative detoxification of carbon monoxide. The complexes
      are designed such that a sheltered void of controllable dimensions encompasses
      the CO binding site. Systematic variations in the available space for the iron
      bound CO produce a wide range of equilibrium binding constants (K(CO)). An x-ray
      structure determination of a CO adduct complex having a crowded CO site reveals
      that the Fe-C identical withO linkage is bent, and further, the distortion
      involves both displacement of the Fe-C vector from the normal to the N(4) plane
      and bending of the Fe-C-O angle.

PMID- 16593096
TI  - Tropospheric concentrations of methylchloroform, CH(3)CCl(3), in January 1978 and
      estimates of the atmospheric residence times for hydrohalocarbons.
AB  - The ground level tropospheric concentrations of CH(3)CCl(3) were measured from 55
      degrees N to 53 degrees S during the time period around Jan. 1, 1978. The
      northern temperate zone concentration of CH(3)CCl(3) averaged 94.6 +/- 4.0 x 10(
      12) by volume. The southern temperate zone concentration averaged 65.2 +/- 1.3 x
      10(-12), for a worldwide average of 80 x 10(-12) by volume. The ratio of
      concentrations between the two zones is 1.45 +/- 0.07. The observed CH(3)CCl(3)
      concentrations correspond to 0.52 +/- 0.05 times the atmospheric release to that
      date, corresponding to an atmospheric residence time of 6.9 +/- 1.2 yr. The
      atmospheric residence times for 22 other hydrohalocarbon molecules were estimated
      in comparison to that of CH(3)CCl(3) through the relative rates of reaction with
      OH radicals.

PMID- 16593097
TI  - Anomalous dispersion of sulfur in quinidine sulfate,
      (C(20)H(25)N(2)O(2))(2)SO(4).2H(2)O: Implications for structure analysis.
AB  - A Patterson-type map computed with Bijvoet differences squared as coefficients,
      (F(h) - F(-h))(2), as recommended by Rossmann, readily yielded the position of
      the S atom. The experiment was performed with Cu Kalpha radiation which is far
      from the absorption edge for sulfur. The coordinates of the remainder of the 54C,
      N, and O atoms were derived by means of partial structure development by use of
      the tangent formula. The latter was used only to effect phase extension, not
      phase refinement. A main purpose of this experiment was to reaffirm, as first
      shown in the investigation of the protein crambin by Hendrickson and Teeter,
      that, in the presence of a large number of lighter atoms, sulfur atoms can be
      located by use of anomalous dispersion at wave-lengths far from the absorption
      edge. The space group is P2(1) with a = 26.718(8) A, b = 6.987(3) A, c =
      10.857(6) A, and beta = 99.51(4) degrees and contains two quinidyl ions, one
      sulfate ion, and two water molecules per asymmetric unit. The conformations of
      the two independent quinidyl ions differ mainly in the torsional angle of the
      bond between the vinyl side chain and the quinuclidine moiety. The R factor is
      4.9% for all 2869 data.

PMID- 16593098
TI  - The kinetic energy change on covalent bond formation.
AB  - Stimulated by an analysis of the classical molecular orbital and valence bond
      descriptions of the two-electron normal covalent bond (both faulty), the argument
      is made that there exist good representations of the kinetic energy change
      DeltaT, on nonpolar covalent bond formation in a diatomic molecule, of the form
      DeltaT(R) = integralF(R - r')S(r')dr'. Here F is a nonlinear response function
      which itself involves the overlap S. The kinetic change is known to satisfy the
      sum rule integral(0) (infinity)DeltaT(R)dR = Z(alpha)Z(beta) exactly; it is shown
      how this can be built into the treatment by the use of Fourier transform methods.
      Also considered is integral(0) (infinity)DeltaT(R)R(2)dR, which is an important
      additional property of the kinetic energy change. Representation of DeltaT(R) as
      a Morse function, already known to be highly accurate, is shown to exactly
      conform to the proposed form.

PMID- 16593099
TI  - Criterion for biholomorphic equivalence of isolated hypersurface singularities.
AB  - Two germs of complex analytic hypersurfaces with isolated singularities are
      biholomorphically equivalent if and only if they have the same dimension and
      their moduli algebras are isomorphic.

PMID- 16593100
TI  - Existence of nonarithmetic monodromy groups.
AB  - In an 1885 paper, E. Picard defined a subgroup Tau(Lambda) of PU(2,1) generated
      by monodromies and depending on parameters Lambda =
      (lambda(1),lambda(2),lambda(3),lambda(4)), 0 < lambda(i) < 1, < lambda(i) < 3,
      lambda(i) + lambda(j) >/= 1, 1 </= i < j </= 4. The family Tau(Lambda) resembles
      the family of groups Tau([unk]) defined in 1978 but is a different family. In
      common with the groups Tau([unk]), (i) Tau(Lambda) is discrete for a finite
      number of Lambda, (ii) Tau(Lambda) is a nonarithmetic lattice for some Lambda,
      and (iii) for all Lambda in [unk](4), there is a compact complex surface
      S(Lambda) with pi(1) [S(Lambda)] of finite index in Tau(Lambda).

PMID- 16593101
TI  - Evolution of DNA sequence organization in mitochondrial genomes of Zea.
AB  - Molecular mechanisms underlying the evolution of mtDNA in maize and three species
      of teosinte have been investigated. By using DNA transfer techniques and cloned
      fragments of maize mtDNA, changes in the position of homologous sequences in
      restriction digests were analyzed in related taxa. The resulting patterns
      indicate general conservation of sequence homology in all four species. One-third
      of the cloned fragments showed sequences conserved in homology and position of
      BamHI restriction fragments. Other fragments produced patterns indicating that
      extensive rearrangement of DNA sequences has taken place. In two cases,
      hybridization patterns revealed major changes in relative abundance of specific
      sequences that we believe are related to the molecular heterogeneity phenomenon
      of maize mtDNA. The evolution of mtDNA in these plants appears dramatically
      different from that in animal mtDNA, where base substitutions may account for
      most of the observed changes in restriction patterns.

PMID- 16593102
TI  - Asparagine amide metabolism in developing cotyledons of soybean.
AB  - Magic-angle single and double cross-polarization (13)C and (15)N NMR spectra have
      been obtained of lyophilized soybean cotyledons cultured on media containing, as
      the only nitrogen source, [4-(13)C, amide-(15)N]asparagine. Single cross
      polarization NMR shows directly and unambiguously that both labels from
      asparagine are incorporated extensively and nonrandomly into protein by the
      developing cotyledon during a 2-week period. A stable-isotope double label tags a
      chemical bond. The metabolic fate of the asparagine double label was followed by
      double cross-polarization NMR using the latter's sensitivity to the dipolar
      coupling between directly bonded (13)C and (15)N. These experiments show that in
      culture the direct incorporation of asparagine (with no scrambling of label)
      accounts for about half of all asparagine residues in soybean protein. This
      conclusion implies the operation of a regulatory apparatus in soybeans for both
      direct utilization and degradation of asparagine in protein synthesis.

PMID- 16593103
TI  - DNA sequence analysis reveals extensive homologies of regions preceding hsp70 and
      alphabeta heat shock genes in Drosophila melanogaster.
AB  - Two kinds of RNA are synthesized at the 87C1 chromosomal locus of Drosophila
      melanogaster in response to heat shock. One of these codes for the major heat
      shock protein, hsp70; the other, alphabeta RNA, derives from tandemly repeated
      alphabeta units consisting of adjacent alpha and beta DNA elements and has no
      identified translation product. Another DNA element, gamma, flanks the 5' ends of
      some alphabeta units. Here we report the complete nucleotide sequence of the 617
      base-pair alpha and the 733-base-pair gamma element as well as a portion of the
      longer beta element. Sequence comparisons between the gamma element and the two
      hsp70 genes at 87C1 reveal that the 406 base pairs of gamma immediately upstream
      from the 5' end of the alphabeta unit exhibit 97.5% homology with the sequences
      at and upstream from the 5' end of the hsp70 genes. A similar homology also
      exists between gamma and an hsp70 gene present at another heat shock locus, 87A7,
      which contains no alphabeta units. These results, in conjunction with previous
      observations, strongly suggest that the coordinate induction by heat shock of the
      hsp70 and alphabeta genes is a consequence of their homologous 5' flanking
      sequences. We propose that this extraordinary degree of sequence conservation
      stems from the recent transposition of alphabeta DNA to the 87C1 locus, an event
      that brought alphabeta sequences adjacent to, and under the regulation of, the
      hsp70 control element.

PMID- 16593104
TI  - Longer-than-unit-length viroid minus strands are present in RNA from infected
      plants.
AB  - Nucleic acids isolated from uninfected and potato spindle tuber viroid-infected
      Rutgers tomato plants were fractionated on agarose gels under two different sets
      of denaturing conditions and hybridized to (125)I-labeled viroid in a series of
      blot hybridization experiments. Complementary strand nucleic acids detected in
      extracts of infected plants were heterogeneous in size, with four discrete bands
      containing molecules approximately 700, 1050, 1500, and 1800 nucleotides long.
      Enzymatic studies indicated that these viroid minus strands are composed
      exclusively of RNA and, as extracted, are present in complexes containing
      extensive double-stranded regions. After treatment with several RNases under
      conditions favoring digestion of single-stranded regions, the high molecular
      weight minus strands can no longer be detected and roughly unit-length minus
      strands appear. A model for the structure of the viroid replication intermediate
      is proposed.

PMID- 16593105
TI  - Abnormal action potentials associated with the Shaker complex locus of
      Drosophila.
AB  - Intracellular recordings of action potentials were made from the cervical giant
      axon in Shaker (Sh) mutants and normal Drosophila. The mutants showed abnormally
      long delays in repolarization. The defect is not due to abnormal Ca(2+) channels,
      because it persists in the presence of Co(2+), a Ca(2+)-channel blocker. On the
      other hand, the K(+)-channel blocker 4-aminopyridine causes a similar effect in
      normal animals, suggesting that the Sh mutant may have abnormal K(+) conductance.
      Gene-dosage analysis of Sh shows that the defect is not due to underproduction of
      an otherwise normal molecule; it may be due to an abnormal molecule produced by
      the mutated gene. Gel electrophoresis failed to detect an abnormal protein,
      suggesting that, if Sh codes for a nervous system protein, it is rare. Genetic
      analysis of the Sh locus indicates three regions. Mutations or chromosome breaks
      in the two flanking regions cause Sh mutant physiology; the central region shows
      a "haplolethal effect"-i.e., heterozygous females are lethal.

PMID- 16593106
TI  - Marginal underdominance at a stable equilibrium.
AB  - An example is given of a stable equilibrium of a deterministic discrete
      generation two-locus, two-allele, model at which marginal (or induced)
      underdominance holds. The example was found by using a numerical search procedure
      that involved picking random equilibria and finding possible fitnesses that would
      lead to those equilibria.

PMID- 16593107
TI  - Effect of basis set on electron populations calculated by using Bader's criterion
      for partitioning electron density between atoms.
AB  - The effect of basis set on Bader's criterion for partitioning electron density
      between atoms is examined. The major effect is on the position of minimum
      electron density along the bond of interest. The 6-31G(**) basis leads to the
      more satisfactory results. The effect of including electron correlation was
      examined via the use of generalized valence bond wavefunctions. The change in the
      electron populations was small. The partitioning of electron density is useful in
      examining the way in which substituents interact with hydrocarbon groups.

PMID- 16593108
TI  - Gas-phase pyrolytic formation and dimerization of benzocyclobutenes: Synthesis of
      [2(4)](1,2,4,5) cyclophane.
AB  - Gas-phase pyrolysis of benzocyclobutenes in a nitrogen stream at 450 degrees C is
      a convenient efficient method for preparing dibenzocyclooctadienes. Application
      of this method to benzo[1,2;4,5]dicyclobutene gives [2(4)](1,2,4,5)cyclophane
      directly. However, under the same reaction conditions, 3,6
      dimethylbenzo[1,2;4,5]dicyclobutene gives the open [2.2]orthocyclophane
      derivative, whose structure has been established by x-ray crystallographic
      analysis of the corresponding iron complex.

PMID- 16593109
TI  - Further perspectives on the charge transfer transitions of blue copper proteins
      and the ligand moieties in stellacyanin.
AB  - The charge transfer spectra of plastocyanin and azurin are analyzed in detail,
      taking into account the structural information that is available. The number and
      relative energies of the low-lying charge transfer bands attributable to cysteine
      and methionine sulfur are considered with reference to the energy levels
      associated with the donor centers and to experimental work on relevant complexes.
      Two cysteine --> Cu(II) charge transfer transitions are assigned to bands that
      occur near 620 nm and near 770 nm. Energy considerations suggest that the
      methionine --> Cu(II) transition occurs in the vicinity of 550 nm for both
      plastocyanin and azurin. The existence of a disulfide linkage in stellacyanin is
      established by thiol titrations, and the possibility exists that the fourth
      ligand in stellacyanin may involve disulfide sulfur. If so, the cystine -->
      Cu(II) transition is also expected to appear around 550 nm.

PMID- 16593110
TI  - Chemistry of acetylene on platinum (111) and (100) surfaces.
AB  - An ultra-high vacuum experimental study of acetylene chemisorption on Pt(111) and
      Pt(100) and of the reaction of hydrogen with the acetylene adsorbate has
      established distinguishing features of carbon-hydrogen bond breaking and making
      processes as a function of pressure, temperature, and surface crystallography.
      The rates for both processes are substantially higher on the Pt(100) surface. Net
      acetylene-hydrogen processes, in the temperature range of 20 degrees C to
      approximately 130 degrees C, are distinctly different on the two surfaces: on
      Pt(100) the net reaction is hydrogen exchange ((1)H-(2)H exchange) and on Pt(111)
      the only detectable reaction is hydrogenation. Stereochemical differences in the
      acetylene adsorbate structure are considered to be a contributing factor to the
      differences in acetylene chemistry on these two surfaces.

PMID- 16593111
TI  - Random walk properties from lattice bond enumeration: Anisotropic diffusion in
      lattices with periodic and randomly distributed scatterers.
AB  - A lattice bond enumeration method recently devised for the study of random walk
      problems is used to rederive, with relative ease, the classic Maxwell-Rayleigh
      formulas for the effective de conductivity of a heterogeneous solid composed of
      periodically (or randomly) arrayed spheres in a medium of a different material.

PMID- 16593112
TI  - Synthesis and determination of configuration of natural 25-hydroxyvitamin D(3)
      26,23-lactone.
AB  - The four stereoisomers of 25-hydroxyvitamin D(3) 26,23-lactone were synthesized
      by a stereoselective lactonization method. Natural 25-hydroxyvitamin D(3) 26,23
      lactone was produced from 25-hydroxy-[3alpha-(3)H]vitamin D(3) by in vitro
      incubation of kidney homogenate prepared from vitamin D-supplemented chickens or
      was isolated from the serum of rats given 1,25-dihydroxyvitamin D(3) and 25
      hydroxy-[3alpha-(3)H]vitamin D(3). The four synthetic isomers and the naturally
      produced 25-hydroxyvitamin D(3) 26,23-lactone were subjected to high-performance
      liquid chromatography in a system capable of separating the four isomers. The
      natural lactone comigrated with synthetic (23S,25R)-25-hydroxyvitamin D(3) 26,23
      lactone, establishing it as the natural vitamin D(3) metabolite.

PMID- 16593113
TI  - Introduction of short-range restrictions in a protein-folding algorithm involving
      a long-range geometrical restriction and short-, medium-, and long-range
      interactions.
AB  - A protein-folding algorithm, based on short-range and geometrical long-range
      restrictions, is applied to bovine pancreatic trypsin inhibitor (BPTI). These
      restrictions are used to define a starting conformation, SI, by means of a space
      filling model of the protein, whose energy is then minimized. The long-range
      restriction is the imposition of the native spatial geometric arrangement of the
      loops (SGAL) formed by the disulfide bonds. The short-range restrictions are
      applied as follows: the (varphi, psi) map of each residue is divided into six
      regions (corresponding to the right- and left-handed alpha-helical, extended,
      right- and left-handed bridge, and coil states) and the individual residues are
      placed in the states of the native structure [although not in conformations with
      the correct values of (varphi, psi)]. Minimization of the energy of SI leads to a
      structure, SF, with a root-mean-square deviation of 4.4 A from NI, a previously
      energy-optimized version of the x-ray structure. SF is closer to the native
      structure than is the structure RF, which was obtained previously by imposing
      only the correct SGAL as a restriction. The energy of SF is much lower than that
      of RF but still larger than the energy of NF (the energy-refined x-ray
      structure).

PMID- 16593114
TI  - Radial distribution function of liquid argon according to significant structure
      theory.
AB  - The significant structure theory of liquids is tested by evaluating the radial
      distribution function. The calculations are based on face-centered cubic quasi
      lattice structure, and the fluctuation in volume is used to describe the thermal
      displacements of molecules. It is shown that the local structure of liquids has
      inhomogeneous distributions. The correlation at long ranges becomes negligible
      because of the fluidized vacancies in our model. The calculations are performed
      for liquid argon, and the results are in good agreement with experiments.

PMID- 16593115
TI  - Uniqueness of solutions of semilinear Poisson equations.
AB  - Let R(n) denote n-dimensional Euclidean space, with n > 1. We study the
      uniqueness of positive solutions u(x), x in R(n), of the semilinear Poisson
      equation Deltau + f(u) = 0 under the assumption that u(x) --> 0 as x -->
      infinity. This type of problem arises in phase transition theory, in population
      genetics, and in the theory of nucleon cores, with various different forms of the
      driving term f(u). For the important model case f(u) = -u + u(p), where p is a
      constant greater than 1, our results show (i) that when the dimension n of the
      underlying space is 2, there is at most one solution (up to translation) for any
      given p and (ii) that when the dimension n is 3, there is at most one solution
      when 1 < p </= 3. In both cases, the solution is radially symmetric and
      monotonically decreasing as one moves outward from the center. For dimensions
      other than 2 or 3, and indeed for the analogous cases of a real dimensional
      parameter n > 1, we obtain corresponding results. We note finally, again for the
      model case, that existence holds for 1 < p < (n + 2)/(n - 2); thus, there remains
      an interesting difference between the parameter ranges for which existence and
      uniqueness are established.

PMID- 16593116
TI  - Boundary behavior of functions holomorphic in domains of finite type.
AB  - We study several notions of distance and ball on the boundary of domains of
      finite type in C(n). We use these notions to develop a theory of maximal
      functions and area integrals for functions holomorphic in such domains.

PMID- 16593117
TI  - Extendability of proper holomorphic mappings and global analytic hypoellipticity
      of the partial differential-Neumann problem.
AB  - IN THIS COMMUNICATION, THE PROOF OF THE FOLLOWING THEOREM IS SKETCHED: If D(1) is
      a bounded domain in C(n) with real analytic boundary whose partial differential
      Neumann problem is globally real analytic hypoelliptic and f is a proper
      holomorphic mapping of D(1) onto a second bounded domain D(2) in C(n) with real
      analytic boundary, then the mapping f extends to be holomorphic in a neighborhood
      of D(1). The proof relies on a transformation formula for the Bergman projection
      under proper holomorphic mappings.

PMID- 16593118
TI  - Molecular basis of auxin-regulated extension growth and role of dextranase.
AB  - The first step in the extension growth of the plant cell is a process in which
      the cell wall becomes ductile or plastic, after which the actual enlargement
      takes place passively under the influence of turgor. The nature of this process
      has not been explained, although much research has been carried out concerning
      it. In the present report, it is shown that a specific enzyme, which is identical
      or nearly so with dextranase (alpha-1,6-D-glucan 6-glucanohydrolase, EC 3.2.1.11)
      and is associated with the cell walls of growing coleoptiles, plays a prominent
      role in this process. The action of this enzyme is dependent on the level of
      growth hormone, auxin, in the tissue. Under its action, certain cell wall
      components are broken down to yield arabinose and glucose. These sugars are also
      released during autolysis of cell wall material. The molecular linkages broken in
      the process are probably the arabinogalactan crosslinks of the hemicellulose
      matrix, which are the main constituents of the wall containing arabinose. This is
      substantiated by the finding that dextranase can break down arabinan and
      compounds containing arabinose chains with the release of arabinose, just as in
      the action of the enzyme on the wall. The breaking of these crosslinks will
      impart the necessary plasticity to the wall for cell extension to occur.

PMID- 16593119
TI  - K/Na-triggered bioluminescence in the oceanic squid Symplectoteuthis
      oualaniensis.
AB  - A distinctive type of luminescent system present in the large dorsal luminous
      organ of the oceanic squid Symplectoteuthis oualaniensis is described. The organ
      produces an intense blue flash of light followed by a rapid decay in light
      intensity. Luminescence originates from numerous oval granules present in the
      luminous organ. The essential light-emitting components are membrane bound.
      Intact granules or washed homogenates of the granules are triggered to emit light
      by monovalent cations such as, in decreasing order of effectiveness, potassium,
      rubidium, sodium, cesium, ammonium, and lithium. Calcium, magnesium, and
      strontium ions do not trigger light emission. Analysis of the kinetics of the
      decay of light intensity suggests that two light-emitting components are
      involved, one decaying faster than the other. The light-emitting reaction has an
      absolute requirement for molecular oxygen. The optimum KCl or NaCl concentration
      is approximately 0.6 M and the optimum pH is approximately 7.8. A free sulfhydryl
      group is essential for activity.

PMID- 16593120
TI  - mRNAs for the immobilization antigens of Paramecium.
AB  - Immobilization antigens of stock 51 of Paramecium tetraurelia were subjected to
      electrophoresis in NaDodSO(4)/polyacrylamide gels. Type A is estimated to have a
      molecular size of 300,000 daltons; H is estimated to be 288,000, D to be 280,000,
      E to be 270,000, B to be 253,000, and C to be 250,000. Poly(A)(+)RNAs have been
      isolated from cells producing these antigens and subjected to electrophoresis in
      methylmercury gels. A major band is found to vary in mobility with antigenic
      type: Its position in preparations derived from paramecia synthesizing antigen A
      indicates a size of 8400 nucleotide residues; its position from paramecia
      synthesizing other antigens indicate H, 8200; D, 7900; E, 7500; B, 7600; and C,
      7000. Because of the sizes and quantities of these RNAs, it is argued that they
      probably represent the mRNAs for the immobilization antigens. It is concluded
      that each immobilization antigen probably consists of a single polypeptide and
      that only one major serotype-determining mRNA is present in each antigenically
      different paramecium.

PMID- 16593122
TI  - Morphology of a novel cyanobacterium and characterization of light-harvesting
      complexes from it: Implications for phycobiliprotein evolution.
AB  - The morphology of the marine cyanobacterium DC-2 and two light-harvesting
      complexes from it have been characterized. DC-2 has an outer cell wall sheath not
      previously observed, the purified phycoerythrin shows many unusual properties
      that distinguish it from all phycoerythrins characterized to date, and isolated
      phycobilisomes have a single absorption band at 640 nm in the phycocyanin
      allophycocyanin region of the spectrum. On the basis of these observations we
      suggest that DC-2, rather than being a member of the Synechococcus group, should
      be placed in its own taxonomic group. In addition, the particular properties of
      the isolated phycoerythrin suggest that it may be representative of an early
      stage in the evolution of the phycoerythrins. These observations are of special
      interest in light of the contribution DC-2 and related cyanobacteria may make to
      global primary productivity.

PMID- 16593121
TI  - Differential transcription in vivo and in vitro of two adjacent maize chloroplast
      genes: The large subunit of ribulosebisphosphate carboxylase and the 2.2-kilobase
      gene.
AB  - The transcription of cloned maize plastid DNA sequences in vitro by maize plastid
      DNA-dependent RNA polymerase has been studied to expose the roles of the enzyme,
      polypeptide cofactors, and DNA sequences in the regulation of gene expression.
      The 4.35-kilobase pair BamHI fragment 9 carries the maize plastid gene for the
      large subunit of ribulosebisphosphate carboxylase and part of the gene for a 2.2
      kilobase RNA. These two genes are separated by approximately 330 base pairs and
      are transcribed divergently. Transcripts of the gene for the large subunit of
      ribulosebisphosphate carboxylase are abundant in bundle sheath cells of maize
      leaves and we show here that transcripts of the 2.2-kilobase RNA gene are present
      in both mesophyll cells and the adjacent bundle sheath cells. In vitro, in the
      presence of the S factor, maize chloroplast DNA-dependent RNA polymerase produces
      a transcript of the gene for the large subunit of ribulose-bisphosphate
      carboxylase with a 5' terminus like that of the corresponding mRNA isolated from
      plastids, transcribes chloroplast DNA sequences of Bam fragment 9 in a chimeric
      plasmid in preference to the vehicle RSF 1030 and, in a ratio of 3:1,
      preferentially transcribes the gene for the large subunit of ribulosebisphosphate
      carboxylase over the 2.2-kilobase RNA gene from supercoiled chimeric plasmid DNA.

PMID- 16593123
TI  - Isolation and amino acid sequence of a morphogenetic peptide from hydra.
AB  - From Anthopleura elegantissima and from Hydra attenuata, a morphogenetic peptide
      the head activator-was isolated in pure form. The sequence of the head activator
      was established by enzymatic and by chemical degradation of the whole peptide or
      fragments thereof and subsequent analysis of the amino acids by micromethods. The
      head activator from both sources was identical and has the sequence:<pGlu-Pro-Pro
      Gly-Gly-Ser-Lys-Val-Ile-Leu-Phe.

PMID- 16593124
TI  - Identification and characterization of double-stranded RNA associated with
      cytoplasmic male sterility in Vicia faba.
AB  - The cytoplasmic male sterility (CMS) trait of at least one line of Vicia faba
      plants is always associated with the presence of high molecular weight double
      stranded RNA in the leaf tissue extracts. Subcellular fractions of leaf tissue
      from CMS and fertile maintainer plants were initially analyzed in an attempt to
      locate, identify, and characterize the genetic material involved with the
      sterility trait. This CMS-associated high molecular weight RNA was found only in
      the cytosol of the "447" male sterile line of V.faba plants and could not be
      isolated from the recurrent parent (maintainer), from lines that had been
      fertility-restored, or from lines that had reverted from the sterile condition.
      We have been able to move the CMS-associated RNA from donor to fertile host
      plants through a dodder bridge. These hots not only contain the RNA but now
      exhibit a male sterile phenotype, as detected by visual examination of the
      flower, the pollen, morphological characteristics, and pollen staining ability.

PMID- 16593125
TI  - Pattern recognition applied to presidential elections in the United States, 1860
      1980: Role of integral social, economic, and political traits.
AB  - The outcome of American presidential elections in 1860-1980 follows certain
      regular patterns which can be described phenomenologically by simple integral
      parameters of "common sense" type.

PMID- 16593126
TI  - Canonical coordinates for plasma and hydrodynamic problems.
AB  - Many nonlinear equations arising in plasma physics, hydrodynamics, and solid
      state physics can be written in Hamiltonian form. The full advantage of this is
      achieved only when the existence of canonical coordinates and momenta is known.
      Here such coordinates are exhibited for three large classes of equations-which
      seem to include almost all known completely integrable Hamiltonian systems.

PMID- 16593127
TI  - Framework for biorthogonal Fourier series.
AB  - Biorthogonal Fourier series occur when applying separation of variables to many
      problems. Here an approach which possesses considerable advantages with respect
      to the standard one is explained.

PMID- 16593128
TI  - Transfer activity coefficients between water and methanol of complexes of some
      univalent and barium ions with dibenzocryptand 2.2.2, cryptand 2.2.2, and 18
      crown-6.
AB  - Stability constants, K(f)LM(n+) (in which L = ligand and M(n+) = metal ion), of
      complexes of sodium, potassium, silver, thallium(I), and barium with
      dibenzocryptand 2.2.2 were determined at 25 degrees C in water and methanol. Also
      determined were transfer activity coefficients between methanol and water of two
      ligands, dibenzocryptand 2.2.2 and 18-crown-6. From these data, transfer activity
      coefficients of complexes of these two ligands with the above cations have been
      calculated. For univalent ion complexes of these ligands and, in addition, for
      such complexes of dibenzo-18-crown-6 and cryptand 2.2.2, the logarithms of the
      transfer activity coefficients are of the order of 2.5 units more positive than
      those of the ligands. Even though methanol is a good hydrogen bond donor, as is
      water, it is concluded that in methanol only the first solvation layer is built
      around an ether oxygen of the uncomplexed ligand as compared with several
      hydration layers in water. Hydrogen bonding to these ether oxygens when these
      ligands are complexed is greatly decreased as a result of ionic M(n+)-O bonding.
      Transfer activity coefficients of the barium complexes are found to be the same
      as those of the ligands. This is attributed to extensive solvation of LBa(2+).

PMID- 16593129
TI  - Restrictions on permissible paths for changing efficiencies of operation of flow
      reactors.
AB  - Sometimes a continuous flow stirred tank reactor can exhibit two or more
      different states of chemical reaction for the same flow rate. If such a situation
      is possible, a state of low reactive efficiency can be converted to one of higher
      efficiency by first decreasing the flow rate and then increasing it to the
      original value. This transition can never be accomplished by first increasing and
      then decreasing the flow rate. Similarly, a state of high reactive efficiency can
      be converted to one of lower efficiency only by first increasing and then
      decreasing the flow rate. These restrictions on permissible order of operations
      seem to differ from restrictions on efficiencies of cyclic heat engines and on
      directions of chemical change in closed systems as derived previously from
      thermodynamics.

PMID- 16593130
TI  - Generation of "bastard" molecular ions from van der Waals clusters:
      Ar(n)(C(2)Cl(4))(m) ions, suspected interlopers in collection of solar neutrinos.
AB  - Gaseous molecular ions containing argon and perchlorethylene, Ar(n)(C(2)Cl(4))(m)
      (+) in which n >/= 1-29 and m >/= 1-4, are produced by electron bombardment of
      van der Waals clusters formed by expanding an Ar/C(2)Cl(4) mixture through a
      supersonic nozzle. Previous attempts to observe such ions in a high-pressure mass
      spectrometer were not successful, as with many other ("bastard") ions that
      similarly lack a stable chemically bound neutral parent molecule. This is
      probably due to dissociation induced by the large exoergicity from charge
      transfer between species that differ greatly in ionization potential. Use of van
      der Waals clusters as parent species avoids entirely the exoergicity problem and
      thus offers a general method to generate bastard ions. The Ar(C(2)Cl(4))(m) (+)
      ions have been suspected of interfering with collection of (37)Ar(+) ions
      produced by the (37)Cl(v,e(-))(37)Ar(+) reaction in the solar neutrino
      observatory. Although, as shown by our results, these ions are stable, they are
      unlikely to inhibit collection on the long time scale of the solar neutrino
      experiment.

PMID- 16593131
TI  - A new family of algebras underlying the Rogers-Ramanujan identities and
      generalizations.
AB  - The classical Rogers-Ramanujan identities have been interpreted by Lepowsky-Milne
      and the present authors in terms of the representation theory of the Euclidean
      Kac-Moody Lie algebra A(1) ((1)). Also, the present authors have introduced
      certain "vertex" differential operators providing a construction of A(1) ((1)) on
      its basic module, and Kac, Kazhdan, and we have generalized this construction to
      a general class of Euclidean Lie algebras. Starting from this viewpoint, we now
      introduce certain new algebras [unk](v) which centralize the action of the
      principal Heisenberg subalgebra of an arbitrary Euclidean Lie algebra [unk] on a
      highest weight [unk]-module V. We state a general (tautological) Rogers-Ramanujan
      type identity, which by our earlier theorem includes the classical identities,
      and we show that [unk](v) can be used to reformulate the general identity. For
      [unk] = A(1) ((1)), we develop the representation theory of [unk](v) in
      considerable detail, allowing us to prove our earlier conjecture that our general
      Rogers-Ramanujan-type identity includes certain identities of Gordon, Andrews,
      and Bressoud. In the process, we construct explicit bases of all of the standard
      and Verma modules of nonzero level for A(1) ((1)), with an explicit realization
      of A(1) ((1)) as operators in each case. The differential operator constructions
      mentioned above correspond to the trivial case [unk](v) = (1) of the present
      theory.

PMID- 16593132
TI  - Cloned DNA sequences complementary to mRNAs encoding precursors to the small
      subunit of ribulose-1,5-bisphosphate carboxylase and a chlorophyll a/b binding
      polypeptide.
AB  - Double-stranded cDNA was synthesized from pea poly(A)-containing mRNA and
      inserted into the Pst I site of the bacterial plasmid pBR322 by the addition of
      synthetic oligonucleotide linkers. Bacterial colonies containing recombinant
      plasmids were detected by hybridization to partially purified mRNAs and further
      characterized by cell-free translation of hybridization-selected mRNAs. To
      confirm the identity of cDNA clones encoding chloroplast polypeptides, we
      incubated translation products derived from complementary mRNAs with intact
      chloroplasts in vitro. After uptake, precursor polypeptides were converted to
      their mature size and identified by fractionation of the chloroplast stroma and
      thylakoid membranes. By using these procedures, we have isolated and
      characterized cDNA clones encoding the two major cytoplasmically synthesized
      chloroplast proteins: the small subunit of ribulose-1,5-bisphosphate carboxylase
      and a constituent polypeptide (polypeptide 15) of the light-harvesting
      chlorophyll a/b-protein complex. Similarly, a third cDNA clone was isolated and
      shown to encode a 22,000-dalton thylakoid membrane polypeptide.

PMID- 16593133
TI  - Identification of the triazine receptor protein as a chloroplast gene product.
AB  - The triazine herbicides inhibit photosynthesis by blocking electron transport at
      the second stable electron acceptor of photosystem II. This electron transport
      component of chloroplast thylakoid membranes is a protein-plastoquinone complex
      termed "B." The polypeptide that is believed to be a component of the B complex
      has recently been identified as a 32- to 34-kilo-dalton polypeptide by using a
      photoaffinity labeling probe, azido-[(14)C]atrazine. A 34-kilodalton polypeptide
      of pea chloroplasts rapidly incorporates [(35)S]methionine in vivo and is also a
      rapidly labeled product of chloroplast-directed protein synthesis. Trypsin
      treatment of membranes tagged with azido-[(14)C]atrazine, [(35)S]methionine in
      vivo, or [(35)S]methionine in isolated intact chloroplasts results in identical,
      sequential alterations of the 34-kilo-dalton polypeptide to species of 32, then
      18 and 16 kilodaltons. From the identical pattern of susceptibility to trypsin we
      conclude that the rapidly synthesized 34-kilodalton polypeptide that is a product
      of chloroplast-directed protein synthesis is identical to the triazine herbicide
      binding protein of photosystem II. Chloroplasts of both triazine-susceptible and
      triazine-resistant biotypes of Amaranthus hybridus synthesize the 34-kilodalton
      polypeptide, but that of the resistant biotype does not bind the herbicide.

PMID- 16593134
TI  - Stoichiometry, inhibitor sensitivity, and organization of manganese associated
      with photosynthetic oxygen evolution.
AB  - Chloroplast thylakoid membranes isolated in the presence of EDTA retain high
      rates of O(2) evolution (>/=340 mumol.h(-1).mg chlorophyll(-1)) but contain no
      Mn(2+) that is detectable by electron paramagnetic resonance (EPR) at room
      temperature. The total Mn(2+) content of these preparations is 4.6 per 400
      chlorophylls; 0.6 Mn(2+) can be released by addition of Ca(2+), a treatment that
      does not affect O(2) evolution. The remaining Mn(2+) (4 per 400 chlorophylls)
      appears to be functionally associated with O(2) evolution activity. Inhibition by
      Tris, NH(2)OH, or heat will release a small fraction of Mn(2+) from these
      membranes ( approximately 25% with Tris, for example). Addition of Ca(2+) further
      enhances Mn(2+) release so that for Tris and for NH(2)OH, 2 and 3, respectively,
      Mn(2+) per 400 chlorophylls are extracted from the O(2)-evolving complex. Based
      on the microwave power-saturation properties of the EPR signal IIf, which arises
      from an intermediate electron carrier in the water splitting process, it appears
      that one of the four Mn(2+) associated with photosystem II is uniquely sensitive
      to Tris. A new model is proposed for the organization and inhibitor sensitivity
      of manganese in the O(2)-evolving complex.

PMID- 16593135
TI  - Prostaglandins: Their role in egg-laying of the cricket Teleogryllus commodus.
AB  - Mating of the Teleogryllus commodus female causes increased oviposition mediated
      by PGE(2), which is synthesized in the female's spermatheca from the precursor,
      arachidonic acid, in the presence of a PG-synthesizing complex. The latter,
      together with sperm, is transferred from the male to the female via a
      spermatophore. Only nanogram quantities of PGE(2) injected into oviduct are
      necessary to simulate mating-induced egg release.

PMID- 16593136
TI  - On the entropy function in sociotechnical systems.
AB  - The entropy function H = -Sigmap(j) log p(j) (p(j) being the probability of a
      system being in state j) and its continuum analogue H = integralp(x) log p(x) dx
      are fundamental in Shannon's theory of information transfer in communication
      systems. It is here shown that the discrete form of H also appears naturally in
      single-lane traffic flow theory. In merchandising, goods flow from a whole-saler
      through a retailer to a customer. Certain features of the process may be deduced
      from price distribution functions derived from Sears Roebuck and Company
      catalogues. It is found that the dispersion in logarithm of catalogue prices of a
      given year has remained about constant, independently of the year, for over 75
      years. From this it may be inferred that the continuum entropy function for the
      variable logarithm of price had inadvertently, through Sears Roebuck policies,
      been maximized for that firm subject to the observed dispersion.

PMID- 16593137
TI  - Unique plasmid-like mitochondrial DNAs from indigenous maize races of Latin
      America.
AB  - Mitochondrial DNA from 81 races of Latin American maize were examined by agarose
      gel electrophoresis. Twelve South American races each contained two plasmid-like
      mtDNA molecules similar to those of the cytoplasmic male-sterile S type (cms-S).
      The plasmid-like elements from all 12 races, designated RU, appear to be
      identical. Both molecules appear in vitro as double-stranded linear DNAs
      terminated by repeated sequences arranged in reverse polarity (terminal inverted
      repeats). The larger molecule of the pair, R-1, contains about 7460 nucleotides.
      It shares considerable homology with the larger plasmid-like molecule of cms-S, S
      1, but is about 1000 nucleotides longer than S-1, has a unique sequence of about
      2576 nucleotides, and also contains a BamHI recognition site not present in S-1,
      R-2, the smaller plasmid-like element, consists of about 5450 nucleotides and
      appears to share complete homology with S-2, the smaller plasmid-like molecule of
      cms-S. Neither pollen sterility nor any other trait has been associated with the
      R-1 and R-2 plasmid-like mtDNAs. The BamHI restriction fragments of total mtDNA
      from the 12 RU cytoplasms display similar patterns, which differ only slightly
      but vividly from that of a normal maize standard, B73 x Mo17. BamHI restriction
      analysis of 22 additional races produced arrays similar to those of the RU
      cytoplasms, but which lacked plasmid-like mtDNAs. The taxonomic significance of
      this digestion pattern and of the RU cytoplasms is discussed. One Mexican race,
      Conico Norteno, has been shown to contain the cms-S cytoplasm.

PMID- 16593138
TI  - RNA intermediates in potato spindle tuber viroid replication.
AB  - Two double-stranded RNA intermediates of viroid replication have been isolated
      from potato spindle tuber viroid (PSTV)-infected tomato tissue and characterized
      by polyacrylamide gel electrophoresis and DNA-RNA hybridization techniques. These
      replicative intermediates contain monomeric circular or linear PSTV strands
      complexed with a multimeric complementary RNA strand. Synchronous synthesis of
      single-stranded PSTV is accompained by a simultaneous marked increase in double
      stranded PSTV RNA; thus, in vivo precursors of the characterized double-stranded
      PSTV RNAs seem to be involved in PSTV replication. A "rolling circle" model for
      viroid replication on a circular PSTV template can accommodate the double
      stranded PSTV RNA species characterized.

PMID- 16593140
TI  - Homozygosity and patch structure in plant populations as a result of nearest
      neighbor pollination.
AB  - The population genetic consequences of nearest-neighbor pollination in an
      outcrossing plant species were investigated through computer simulations. The
      genetic system consisted of two alleles at a single locus in a self-incompatible
      plant that mates by random pollen transfer from a neighboring individual.
      Beginning with a random distribution of genotypes, restricted pollen and seed
      dispersal were applied each generation to 10,000 individuals spaced uniformly on
      a square grid. This restricted gene flow caused inbreeding, a rapid increase in
      homozygosity, and striking microgeographic differentiation of the populations.
      Patches of homozygotes bordered by heterozygotes formed quickly and persisted for
      many generations. Thus, high levels of inbreeding, homozygosity, and patchiness
      in the spatial distribution of genotypes are expected in plant populations with
      breeding systems based on nearest-neighbor pollination, and such observations
      require no explanation by natural selection or other deterministic forces.

PMID- 16593139
TI  - Specific cell-cell contacts are essential for induction of gene expression during
      differentiation of Dictyostelium discoideum.
AB  - Postaggregation Dictyostelium discoideum cells contain 2000-3000 mRNA species
      that are absent from pre-aggregation cells. These aggregation-dependent sequences
      compose 30% of the mass of the late mRNA and represent the transcription products
      of an additional 11% of the single-copy genome. By analysis of mutants that are
      blocked at different stages of differentiation, we show that induction of
      expression of these genes is correlated with the formation of tight cell-cell
      contacts that resist EDTA. In particular, mutants that exhibit chemotaxis and
      aggregate to form loose mounds but do not form cell-cell contacts that resist
      EDTA fail to induce these late mRNA and protein species. By contrast, mutants
      that form normal contacts but progress no further through development do express
      the late mRNA species. Thus, interactions at the cell surface are involved in
      developmental induction of a large group of coregulated mRNAs. We have employed
      two independent assays for these developmentally regulated mRNAs: hybridization
      of gel-separated RNAs to cloned nuclear DNAs and hybridization of mRNA to a cDNA
      probe specific for the population of 2000-3000 regulated sequences.

PMID- 16593141
TI  - Identification and characterization of the ecdysterone receptor in Drosophila
      melanogaster by photoaffinity labeling.
AB  - Salivary glands of third-instar larvae of Drosophila melanogaster as well as
      Drosophila K(c) tissue culture cells have been irradiated in the presence of
      ecdysterone. Irradiation covalently links ecdysterone to a single cellular
      protein, which is similar, if not identical, in salivary glands and in K(c)
      cells. This protein has a molecular weight of 130,000 and it has the
      characteristics of a typical hormone-receptor molecule in terms of hormone
      binding properties, translocation into the nucleus, and sedimentation
      characteristics. The yield of the photoinduced bonding of ecdysterone to receptor
      protein is around 15%. Ponasterone A competed with ecdysterone for the bonding.
      Also, ponasterone A itself reacted upon photoactivation with the beta-ecdysterone
      receptor protein in Drosophila tissue culture cells. We have previously shown
      that ecdysterone can be bonded upon irradiation to specific hormone-controlled
      puffs of polytene chromosomes of D. melanogaster third-instar larvae [Gronemeyer,
      H. & Pongs, O. (1980) Proc. Natl. Acad. Sci. USA 77, 2108-2112]. Because we have
      now identified the molecular target of the ecdysterone photoreaction, these data
      show that a hormone-receptor complex translocates to the nucleus and directly
      binds to the genes, which are under hormonal control. A quantitative assay of
      hormone-receptor complex in K(c) cells before and after hormone stimulation
      showed that ecdysterone does not regulate the synthesis and the available amount
      of its receptor. It was also observed that the translocated hormone-receptor
      complex resides in the nucleus as long as the hormone is present in the tissue
      culture medium.

PMID- 16593142
TI  - Octopine synthase mRNA isolated from sunflower crown gall callus is homologous to
      the Ti plasmid of Agrobacterium tumefaciens.
AB  - We have shown that the structural gene for octopine synthase (a crown gall
      specific enzyme) is located in a central portion of the T-DNA that came from the
      Ti plasmid of agrobacterium tumefaciens and is expressed after it has been
      transferred to the plant cells. Polyadenylylated RNA was prepared from polysomes
      isolated from an octopine-producing crown gall callus and purified by selective
      hybridization to one of five recombinant plasmids. Each such plasmid contained a
      different fragment of T-DNA of pTi-15955 (octopine-type Ti plasmid). Purified
      mRNA was translated in vitro in rabbit reticulocyte lysates, and the translation
      products were immunoprecipitated with antibody against octopine synthase. Total
      and immunoprecipitated products were characterized by their molecular weights. A
      polypeptide of M(r) 40,000 (the same as authentic octopine synthase) was
      synthesized in vitro by crown gall mRNA selectively hybridized to three of the
      five fragments of T-DNA and precipitated with antibody against octopine synthase.
      This polypeptide was not immunoprecipitated with normal rabbit antibody nor was
      it synthesized when mRNA from the habituated callus was substituted. A mRNA 1500
      bases long was detected when total mRNA was fractionated on an agarose gel,
      transferred to nitrocellulose, and used for hybridization to three of the five
      (32)P-labeled T-DNA fragments. This apparent mRNA for octopine synthase
      hybridized to the same three fragments of T-DNA as the mRNA for the M(r) 40,000
      polypeptide and was not detected in the habituated callus.

PMID- 16593143
TI  - Sexual dimorphism in Ramapithecinae.
AB  - The Ramapithecinae are an extinct, mainly Miocene group of hominoids comprising
      the genera Sivapithecus and Gigantopithecus. Ouranopithecus and Ramapithecus are
      other included genera, here regarded as invalid. Cladistically, ramapithecines
      are hominid, although, in most aspects of their anatomy, they remain very
      primitive or ape-like. Miocene ramapithecines show reduced sexual dimorphism in
      canine size. In this respect they resemble Pliocene/Recent hominids, not extant
      great apes (which have highly dimorphic canines). Reduced dimorphism in canine
      size is an important shared derived feature indicating the hominid status of
      ramapithecines. Among living anthropoids, a significant association has been
      observed between a monogamous social structure and low canine dimorphism. This
      supports the inference that ramapithecines may have been monogamous.

PMID- 16593144
TI  - Giant circular dichroism of high molecular weight chlorophyllide-apomyoglobin
      complexes.
AB  - Chlorophyllide a and the apoprotein of myoglobin (Mb) spontaneously form three
      types of complex. The M (M(r) approximately 3 x 10(5)) and H (M(r) >/= 4 x 10(6))
      complexes, but not the L (M(r) approximately 1.7 x 10(4)), display a circular
      dichroism (CD) spectrum that is highly red-shifted, nonconservative, and very
      intense-characteristics shared by the CD spectra of reaction center complexes
      from purple photosynthetic bacteria. At its 710-nm peak, the H complex CD
      spectrum has a larger magnitude, 0.06 differential absorbance per unit total
      absorbance, than has been reported for chlorophyll in any medium.

PMID- 16593145
TI  - Picosecond photochemistry of a cofacial diporphyrin containing iron(III) and
      zinc(II): Mimicking electron transfer between cytochrome c and the primary
      electron donor in reaction centers of photosynthetic bacteria.
AB  - Comparison of picosecond kinetic and spectroscopic data for Zn octaethylporphine
      and Fe(III)Cl octaethylporphine with that for Zn-Fe(III)Cl, a cofacial
      diporphyrin composed of a Zn porphyrin covalently bound to an Fe(III)Cl porphyrin
      with two chains of five atoms each, supports the assignment of a light-driven
      electron transfer (k > 10(11)s(-1)) within Zn-Fe(III)Cl to form [Zn(+).
      Fe(II)]Cl. The kinetics (k approximately 10(10)s(-1)) and thermodynamics of the
      reverse electron transfer are compared to those of a similar electron transfer in
      bacterial photosynthesis, the reduction of an oxidized bacteriochlorophyll dimer,
      (BChl)(2) (+)., by Fe(II) cytochrome c.

PMID- 16593146
TI  - Early auxin-regulated polyadenylylated mRNA sequences in pea stem tissue.
AB  - Polyadenylylated mRNA from etiolated pea stem segments treated with or without 20
      muM indoleacetic acid (IAA) for various periods of time was assayed by
      translating it in a wheat germ extract containing [(35)S]methionine and
      separating the translation products by two-dimensional gel electrophoresis.
      Within 2 hr IAA causes at least five mRNA sequences to increase in translational
      activity, relative to initial levels and to simultaneous controls; three of these
      rise significantly within 20 min after exposure of tissue to IAA but are
      apparently not elevated at 10 min, whereas the others begin to increase at
      successive times later than 30 min, and still others begin to change only later
      than 2 hr. These observations indicate an early, highly selective IAA regulation
      of mRNA amounts or activities, becoming progressively more extensive with time.
      The earliest detected enhancement seems close to the primary action of IAA but
      appears not to be rapid enough to be responsible for auxin induction of cell
      enlargement.

PMID- 16593147
TI  - Simulated and empiric wind pollination patterns of conifer ovulate cones.
AB  - Wind tunnel analyses of conifer ovulate cones indicate that the total geometry of
      the cone enhances the probability of pollen entrapment. Aerodynamic
      characteristics of cone scale-bract complexes are such that suspended pollen is
      directed toward the micropyles of attached ovules. Within the taxa examined,
      there appears to be a preferential entrapment by ovulate cones of pollen of the
      same species. The data are interpreted as evidence for an aerodynamic reciprocity
      between wind-suspended pollen and the structure of ovulate cones which increases
      the frequency of pollination and the potential for fertilization.

PMID- 16593148
TI  - Inheritance and expression of lysine plus threonine resistance selected in maize
      tissue culture.
AB  - Selection for resistance to growth inhibition by lysine plus threonine in
      equimolar concentrations (LT) in tissue cultures of maize yielded a stable
      resistant line, LT19. Genetic analysis of progeny of plants regenerated from LT19
      showed that LT resistance was inherited as a single dominant nuclear gene,
      temporarily designated Ltr(*)-19. Tissue cultures initiated from resistant
      embryos required 5-10 times higher levels of LT to inhibit growth than did
      cultures from LT-sensitive embryos. LT resistance in Ltr(*)-19 was expressed as
      much reduced inhibition of root and shoot growth in the presence of LT. The free
      pool of threonine was increased 6 times in cultures initiated from immature
      embryos of LT-resistant plants, and 75-100 times in kernels homozygous for Ltr(*)
      19, as compared to cultures and kernels from LT-sensitive embryos and plants,
      respectively. Overproduction of free threonine increased the total threonine
      content in homozygous Ltr(*)-19 kernels by 33-59%. The results demonstrate that
      LT resistance selected with tissue culture methods is heritable and is expressed
      in cultures, seedlings, and kernels. Furthermore, they demonstrate a method to
      obtain amino acid-overproducer mutants in maize, which have the potential to
      increase substantially specific amino acids in kernels. The capability to
      increase specifically the nutritionally limiting amino acid(s) could have
      important nutritional implications for the grain of cereals and other crops.

PMID- 16593149
TI  - Opioids regulate cGMP formation in cloned neuroblastoma cells.
AB  - Opioid agonists caused a rapid dose-related elevation of the cGMP content of
      N4TG1 murine neuroblastoma cells. An excellent correlation was found between the
      rank order of potency of agonists in stimulating cGMP accumulation and in
      displacing [(3)H]etorphine ([(3)H]ETP) bound to intact cells. The narcotic
      antagonists naloxone and diprenorphine failed to increase cGMP content; moreover,
      in the presence of 5 muM naloxone, the EC(50) of ETP increased from approximately
      9 nM to > 1 muM. N4TG1 cells that had been incubated for 20 min with 0.32 muM ETP
      and thoroughly washed displayed a marked loss in sensitivity to subsequent ETP
      challenge. This desensitization was characterized by a 40-50% decrease in maximal
      response and an increase in the apparent K(a) of ETP from 4 to 50 nM.
      Desensitization was complete after a 7-min incubation with 0.32 muM ETP (t((1/2))
      approximately 1 min) and was only slowly reversible (t((1/2)) > 60 min). Naloxone
      (5 muM) and diprenorphine (0.1 muM) failed to elicit desensitization, but they
      blocked ETP-induced desensitization. Dextrophan and (+)-ethylketazocine were <1%
      as effective as levorphanol and (-)-ethylketazocine, respectively, in both
      stimulating cGMP accumulation and inducing desensitization. When the binding of
      [(3)H]ETP (0.2-20 nM) was examined under identical experimental conditions, cells
      that were completely desensitized by incubation with ETP (7 min with 0.32 muM or
      20 min with 15 nM) showed no loss of high-affinity recognition sites. After
      longer incubation with ETP (0.32 muM for 20-60 min), the maximal binding of
      [(3)H]ETP was reduced 17-41%. The specific short-term desensitization of cGMP
      accumulation is not mediated or accompanied by a decrement in the number of
      agonist binding sites.

PMID- 16593150
TI  - Aerial dispersal and drying of Peronospora tabacina conidia in tobacco shade
      tents.
AB  - Blue mold of tobacco is caused by the fungus Peronospora tabacina. Its spores are
      released in the morning when the relative humidity falls, but they require free
      water for germination. Traditionally, the walls of the shade tents are raised to
      control the pathogen by drying leaves. We show that raising the walls does not
      materially speed drying. It does, however, increase the wind speed at least 20 m
      inside the tent and spread spores farther. Because germination is not reduced,
      raising the walls may actually spread blue mold.

PMID- 16593151
TI  - Photochemical generation of carbon monoxide and hydrogen by reduction of carbon
      dioxide and water under visible light irradiation.
AB  - Visible light irradiation of solutions of Ru(2,2'-bipyridine)(3) (2+), cobalt(II)
      chloride, and carbon dioxide in acetonitrile/water/triethylamine generates
      simultaneously carbon monoxide and hydrogen. The reaction involves photoinduced
      reduction of CO(2) and H(2)O, triethylamine serving as electron donor in the
      Ru(2,2'-bipyridine)(3) (2+)/Co(2+) system. The amount of gas (CO + H(2)) produced
      and the selectivity ratio CO/H(2) depend markedly on the composition of the
      system. Addition of free bipyridine strongly decreases CO generation but
      increases H(2) production. With different tertiary amines, NR(3), both the
      quantity (CO + H(2)) and the ratio CO/H(2) increase markedly along the sequence R
      = methyl, ethyl, propyl. Higher selectivity for CO(2) reduction to CO in
      preference to water reduction occurs when triethanolamine is used instead of
      triethylamine. CoCl(2) is the most efficient mediator for both CO and H(2)
      generation and specifically promotes CO formation, whereas salts of other cations
      studied only yield H(2). The mechanism of the reaction may involve intermediate
      formation of Co(I) species. These processes represent an abiotic photosynthetic
      system allowing simultaneous generation of CO and H(2) and regulation of the
      CO/H(2) ratio. Mechanistic studies and explorations of other components that may
      increase efficiency and product selectivity should be carried out. The results
      obtained are also of significance for solar energy conversion with consumption of
      a pollutant, CO(2).

PMID- 16593152
TI  - Circulant orbitals and the electron-correlation problem.
AB  - Circulant, as well as canonical, orbitals are used in the different orbitals for
      different spins method for treating electron correlation. Circulant orbitals
      provide a theoretical justification for the use of a single parameter, even when
      the canonical orbitals have widely different orbital energies. Illustrative
      calculations on the ground state of the Be atom show the importance of choosing
      the correct "pairs" in the method. A two-parameter version of the conventional
      method gives 74% of the improvement obtained by a full configuration-interaction
      treatment using 20 linear parameters, while a one-parameter linear combination of
      two different coupling schemes of the circulant method gives approximately 61%.
      The latter wavefunction provides a compact description of the electron
      correlation.

PMID- 16593153
TI  - Symplectic geometry and positivity of pseudo-differential operators.
AB  - In this paper we establish positivity for pseudo-differential operators under a
      condition that is essentially also necessary. The proof is based on a
      microlocalization procedure and a geometric lemma.

PMID- 16593154
TI  - On a new gap phenomenon in riemannian geometry.
AB  - This note announces some theorems that show that the flat metric of euclidean
      space has no nearby nonflat complete metric with the property that its curvature
      keeps a sign and is "uniformly small" in a sense made precise here.

PMID- 16593155
TI  - Relative equilibria of vortices in two dimensions.
AB  - An old problem of the evolution of finitely many interacting point vortices in
      the plane is shown to be amenable to investigation by critical point theory in a
      way that is identical to the study of the planar n-body problem of celestial
      mechanics. For any choice of positive circulations of the vortices it is shown by
      critical point theory applied to Kirchhoff's function that there are many
      relative equilibria configurations. Each of these configurations gives rise to a
      stationary configuration of the vortices in a suitably chosen rotating coordinate
      system. A sharp lower bound on the number of stationary vortex configurations for
      the problem of point vortices interacting in the plane is given. The problem of
      point vortices in a circular disk is defined and it is shown that these estimates
      hold for stationary configurations of small size.

PMID- 16593156
TI  - Identification of thymidine-5'-aldehyde at DNA strand breaks induced by
      neocarzinostatin chromophore.
AB  - Snake venom phosphodiesterase or endonuclease S1 digestion of neocarzinostatin
      chromophore-treated DNA, labeled in its thymidine residues, liberates an unusual
      labeled nucleoside from the 5' end of a drug-induced break. This substance,
      isolated by reverse-phase HPLC, possesses carbons from both the thymine and the
      deoxyribose moieties of thymidine in the DNA but, unlike thymidine, is readily
      degraded at pH 12 to thymine and a sugar fragment. The altered nucleoside was
      shown to contain a carbonyl group by its reduction with NaBH(4) to form a
      substance that has the chromatographic properties of thymidine and by its
      reaction with various hydrazines to form the respective hydrazone derivatives;
      the carbonyl exists as the 5' aldehyde as shown by its mild chemical oxidation to
      the carboxylic acid with simultaneous loss of the 5' (3)H. Mass spectral analysis
      showed a fragmentation pattern compatible with the structure thymidine-5'
      aldehyde. These data indicate that the nonprotein chromophore of
      neocarzinostatin, in the presence of a reducing substance (2-mercaptoethanol) and
      molecular oxygen, selectively oxidizes the 5' carbon of nucleosides in DNA to the
      aldehyde, resulting in a strand break and a DNA fragment bearing nucleoside-5'
      aldehyde at its 5' end.

PMID- 16593157
TI  - Complete nucleotide sequence of a soybean actin gene.
AB  - Soybean contains a small multigene family of actin-related sequences. We have
      determined the complete nucleotide sequence of a soybean actin gene carried on
      the recombinant plasmid pSAc3. As deduced from the nucleotide sequence, this
      soybean actin is composed of 376 amino acids. Compared to other eukaryotic
      actins, pSAc3 actin has a deletion of one amino acid between residues 118 and
      122. The initiator methionine is followed by alanine, which is not found at this
      position in other eukaryotic actins. pSAc3 actin differs, in primary sequence,
      more from fungal and animal actins than any of the known nonplant actins differ
      from each other. pSAc3 actin appears to be related to both cytoplasmic and muscle
      specific actins in the location of specific NH(2)-terminal amino acids. The
      coding sequence is interrupted by three small introns, each less than 90 base
      pairs long. The splice junctions are similar to those found in other eukaryotic
      genes, suggesting the presence of a similar splicing apparatus in higher plants.
      Introns 1 and 3 interrupt the reading frame after codons 20 and 355,
      respectively. Intron 2 splits a glycine codon at position 151. None of these
      intron positions is conserved relative to the positions of introns in other actin
      genes examined.

PMID- 16593158
TI  - Oriented properties of the chlorophylls: Electronic absorption spectroscopy of
      orthorhombic pyrochlorophyllide a-apomyoglobin single crystals.
AB  - The orientations of the transition dipole moments in chlorophyll (Chl) are among
      the most useful spectroscopic properties for determining macromolecular
      architecture in photosynthetic complexes; however, the relationships between
      these orientations and the Chl molecular geometry are unknown. In order to solve
      this problem, we have prepared single crystals of the synthetic 1:1 complex
      between pyrochlorophyllide a and apomyoglobin. The protein crystallizes readily
      in the orthorhombic (B) form, space group P2(1)2(1)2(1), and the unit cell
      dimensions are determined to be within 0.5% of those for native MetMb crystals of
      the same type. These green crystals are highly dichroic, and the strong
      absorption along the crystallographic a axis in the Q(y) band is red-shifted by
      about 9 nm, relative to the corresponding feature in a solution of the protein.
      Although the crystal structure for native Mb in this space group has not been
      determined, the direction cosines of the heme normal relative to the crystal axes
      have been measured. By using these values, an appropriate trigonometric analysis,
      and the measured polarized single-crystal spectra, the orientation of the Chl
      transition dipole moment for the Q(y) transition can be specified relative to the
      crystal axes. With the completion of the protein crystal structure, this result
      will lead directly to the orientations of the optical transition dipole moments
      relative to the molecular geometry. The effects of vibronic coupling and the
      protein environment on the absorption properties of Chl are discussed in detail.

PMID- 16593159
TI  - Regulation of sulfate uptake in carrot cells: Properties of a hypercontrolled
      variant.
AB  - Sulfate uptake in haploid carrot cultures can be experimentally controlled by the
      sulfur source provided for growth. The rate of sulfate uptake is low in cells
      grown on cystine or sulfate and high in sulfur-starved cells. A selenate
      resistant variant cell line has been isolated from a haploid carrot line. The
      variant shows hypersuppression of sulfate uptake by cystine and essentially
      normal control by the other treatments. While both lines efflux intracellular
      sulfate in the presence of external sulfate, the rate of efflux from the variant
      is 4-6 times higher at comparable levels of initial intracellular sulfate.
      Further, properties of the efflux and uptake in both lines suggest that they are
      mediated by the same system. We propose that the variant possesses an altered
      uptake-efflux system that is more readily reversed and more subject to control by
      some metabolite derived from cystine.

PMID- 16593160
TI  - Assortment of encounters and evolution of cooperativeness.
AB  - The method of evolutionary stable strategies (ESS), in its current form, is
      confronted with a difficulty when it tries to explain how some social behaviors
      initiate their evolution. We show that this difficulty may be removed by changing
      the assumption made tacitly in game theory (and in ESS) of randomness of meetings
      or encounters. In reality, such randomness seems to be rare in nature. Family,
      population and social structure, customs, and habits impose various types of
      deviation from randomness. Introducing nonrandomness of meeting in a way formally
      similar to assortative mating, we show that the bar to initial increase of
      inherited cooperative or altruistic behaviors can be removed, provided there is
      sufficient assortment of meetings. Family structure may cause contacts
      predominantly between certain types of relatives, and one can reconstruct some
      results of classical kin selection in terms of evolutionary stable strategy with
      assortative meetings. Neighbor effects and group selection might be similarly
      treated. Assortment need not be a passive consequence of population and social
      structure, but it can also be actively pursued. Behaviors favoring the choice of
      cooperative companions will have the effect of favoring the evolution of
      cooperativeness. It can be shown that discrimination in the choice of companions,
      especially if combined with assortment, can favor the development of
      cooperativeness, making initial increase of cooperative behavior possible even at
      levels of assortment passively imposed which would not be adequate, per se, to
      guarantee the increase of cooperativeness. It is possible that, in some cases,
      cooperativeness and behavior favoring some type of assortment are coselected.

PMID- 16593161
TI  - Special phase invariant formulas of higher order: Expected values.
AB  - Formulas for the cosines of the higher-order phase invariants that arise in
      crystal structure analysis are derived as expected values from determinantal
      joint probability distributions. The values of the cosines of the invariants are
      expressed in terms of averages over simple functions of known structure factor
      magnitudes. The formulas are termed "special" to distinguish them from formulas
      that have more general averages. The latter will be presented in a future
      publication. The best opportunity for obtaining useful information from these
      formulas is provided by embedded seminvariants formed from the invariants by use
      of relationships among the phases that arise from the space group symmetries.

PMID- 16593162
TI  - Intensity changes in the Doppler effect.
AB  - When a source moves in any direction, the source strength and the frequencies are
      altered by the Doppler effect. It is shown that the source strength divided by
      the cube of the frequency is a Lorentz invariant.

PMID- 16593163
TI  - Extension of the method of partial retention of diatomic differential overlap to
      second row atoms and transition metals.
AB  - The method of partial retention of diatomic differential overlap (PRDDO) has been
      extended to the elements through the first transition series. A minimum basis set
      of Slatertype orbitals is employed, with optional 3d functions on atoms in the
      second major row. The 3d shell for transition metal atoms is a fixed-contracted
      double-zeta combination of Slater orbitals. The method retains the basic n(3)
      dependency inherent in PRDDO. Limited one-center parameterization and empirical
      two-center exchange integrals are included. The overall accuracy of the approach
      is comparable to that of the PRDDO method as previously applied to molecules
      containing first-row atoms only.

PMID- 16593164
TI  - Molecular dynamics of an alpha-helical polypeptide: Temperature dependence and
      deviation from harmonic behavior.
AB  - The mean square amplitudes of atomic fluctuations for a polypeptide (decaglycine)
      alpha-helix evaluated from molecular dynamics simulations at seven temperatures
      between 5 and 300 K are compared with analytic harmonic results and with
      experimental values. Above 100 K the harmonic approximation significantly
      underestimates the amplitudes of the displacements. Analysis of the time
      dependence of the fluctuations shows that low-frequency modes (<75 cm(-1))
      dominate the atomic fluctuations and that there is a contribution with a very
      long relaxation time (>10 ps). Quantum corrections to the amplitude of the
      fluctuations are found to be small above 50 K. The mean square amplitudes
      obtained from the molecular dynamics simulations are compared with the values
      derived from x-ray temperature (Debye-Waller) factors for metmyoglobin (80, 250,
      and 300 K) and ferrocytochrome c (300 K).

PMID- 16593165
TI  - High-resolution solid-state NMR of quadrupolar nuclei.
AB  - We report the observation of high-resolution solid-state NMR spectra of (23)Na (I
      = [unk]), (27)Al (I = [unk]) and (51)V (I = [unk]) in various inorganic systems.
      We show that, contrary to popular belief, relatively high-resolution (
      approximately 10 ppm linewidth) spectra may be obtained from quadrupolar systems,
      in which electric quadrupole coupling constants (e(2)qQ/h) are in the range
      approximately 1-5 MHz, by means of observation of the ((1/2), -(1/2)) spin
      transition. The ((1/2), -(1/2)) transition for all nonintegral spin quadrupolar
      nuclei (I = [unk], [unk], [unk], or [unk]) is only normally broadened by dipolar,
      chemical shift (or Knight shift) anisotropy or second-order quadrupolar effects,
      all of which are to a greater or lesser extent averaged under fast magic-angle
      sample rotation. In the case of (23)Na and (27)Al, high-resolution spectra of
      (23)NaNO(3) (e(2)qQ/h approximately 300 kHz) and alpha-(27)Al(2)O(3) (e(2)qQ/h
      approximately 2-3 MHz) are presented; in the case of (51)V(2)O(5) (e(2)qQ/h
      approximately 800 kHz), rotational echo decays are observed due to the presence
      of a approximately 10(3)-ppm chemical shift anisotropy. The observation of high
      resolution solid-state spectra of systems having spins I = [unk], [unk], and
      [unk] in asymmetric environments opens up the possibility of examining about two
      out of three nuclei by solid-state NMR that were previously thought of as
      "inaccessible" due to the presence of large (a few megahertz) quadrupole coupling
      constants. Preliminary results for an I = [unk] system, (93)Nb, having e(2)qQ/h
      approximately 19.5 MHz, are also reported.

PMID- 16593166
TI  - Rate constant of vibrational redistribution in molecules using adiabatic
      approximation model.
AB  - By means of the proposed adiabatic approximation model for vibrational
      redistribution [Lin, S. H. (1980) Chem. Phys. Lett. 70, 492-499], the
      calculations of various rate constants caused by different couplings have been
      given in detail. By two methods it has been demonstrated that the rate constant
      caused by the Born-Oppenheimer mechanism, corrected by the non-Condon
      approximation, has the same order of magnitude as that contributed by the
      anharmonic mechanism. Furthermore, the important effect of molecular rotation on
      the rate constant based on the Coriolis coupling has been demonstrated.

PMID- 16593167
TI  - Reliability of the pair-defect-sum approximation for the strength of valence-bond
      orbitals.
AB  - The pair-defect-sum approximation to the bond strength of a hybrid orbital
      (angular wave functions only) is compared to the rigorous value as a function of
      bond angle for seven types of bonding situations, with between three and eight
      bond directions equivalent by geometrical symmetry operations and with only one
      independent bond angle. The approximation is seen to be an excellent one in all
      cases, and the results provide a rationale for the application of this
      approximation to a variety of problems.

PMID- 16593168
TI  - Methane: Interhemispheric concentration gradient and atmospheric residence time.
AB  - The ground level concentrations of methane in the atmosphere have been measured
      to be in the range from 1.45 to 1.62 parts per million by volume (ppmv) of dry
      air in remote locations between 62 degrees N and 54 degrees S latitudes during
      the time period from November 1977 to July 1979. The average (+/-rms)
      concentration for the northern hemisphere was 1.57 +/- 0.02 ppmv in January 1978
      and 1.59 +/- 0.02 in July 1979. The average concentration in the southern
      hemisphere was lower-1.47 +/- 0.02 in January 1978 and 1.51 +/- 0.01 in July
      1979. The ratio of concentrations between the two hemispheres was 1.068 +/- 0.016
      in January 1978 and 1.055 +/- 0.013 in July 1979, for an average of 1.06 +/-
      0.01. The higher concentrations in the northern hemisphere require either that
      the sources of methane lie preferentially in the northern hemisphere or that the
      removal processes operate more rapidly in the southern hemisphere or both. The
      primary removal process for CH(4) is reaction with tropospheric OH radicals and
      its estimated atmospheric lifetime is 10.5 +/- 1.8 yr. The observed
      interhemispheric gradient is consistent with this lifetime and preferential
      release of methane in the northern hemisphere. Measurements taken in the Amazon
      basin region indicate the presence of a substantial source of methane in that
      area.

PMID- 16593169
TI  - Normal nonmetrizable Moore space from continuum hypothesis or nonexistence of
      inner models with measurable cardinals.
AB  - Assuming the continuum hypothesis, a normal nonmetrizable Moore space is
      constructed. This answers a question raised by F. B. Jones in 1931, using an
      axiom well known at that time. For the construction, a consequence of the
      continuum hypothesis that also follows from the nonexistence of an inner model
      with a measurable cardinal is used. Hence, it is shown that to prove the
      consistency of the statement that all normal Moore spaces are metrizable one must
      assume the consistency of the statement that measurable cardinals exist.

PMID- 16593170
TI  - Liposome-mediated delivery of tobacco mosaic virus RNA into tobacco protoplasts:
      A sensitive assay for monitoring liposome-protoplast interactions.
AB  - Tobacco mosaic virus (TMV) RNA was encapsulated in large, unilamellar
      phospholipid vesicles (liposomes), and the encapsulated TMV RNA was shown to be
      infectious when incubated with tobacco protoplasts under appropriate conditions.
      Maximal virus production in protoplasts was observed after their incubation with
      TMV RNA entrapped in phosphatidylserine/cholesterol liposomes. Infection was
      dependent on the presence of polyalcohols in the incubation mixture. Other
      parameters, such as the extent of vesicle binding, the cell-induced leakage of
      vesicle contents, and the degree of liposome toxicity were shown to be important
      in determining the efficiency of infectivity. Liposome-mediated delivery offers
      an efficient and reproducible method for introducing RNA into plant protoplasts.

PMID- 16593171
TI  - Linkage disequilibrium due to random genetic drift in finite subdivided
      populations.
AB  - In order to clarify the mechanisms responsible for the observed linkage
      disequilibrium, such as that found between markers in the major
      histocompatibility complex of man and mouse, linkage disequilibrium between two
      linked loci was studied for a finite population with a subdivided structure. The
      infinite allele model was used. In analogy with the subdivision of the inbreeding
      coefficient, the linkage disequilibrium coefficient was subdivided, and various
      variance components of disequilibrium were defined. It was found that the
      disequilibrium components may get very large when migration is limited if the
      correlation of alleles at the two loci within a colony is taken relative to that
      of the entire population. In other words, with limited migration, random genetic
      drift of gamete types prevails in each colony. A possible test in which the
      variance components of disequilibrium are compared is suggested; the test
      discriminates between epistatic natural selection and limited migration, showing
      the former as the main cause of the observed linkage disequilibrium. It is
      pointed out that the major histocompatibility complex polymorphism is in accord
      with the population genetics model of multigene families that incorporate gene
      conversion or double unequal crossing-over between the loci in the supergene
      family.

PMID- 16593172
TI  - Corticotropin and beta-endorphin-like materials are native to unicellular
      organisms.
AB  - Multiple molecular forms of immunoreactive corticotropin (ACTH) and beta
      endorphin were present in extracts of a unicellular eukaryote (Tetrahymena
      pyriformis). One form of immunoreactive ACTH reacted similarly with two different
      ACTH antisera (one specific for the 11-24 sequence and the other with
      determinants within sequences 1-14 and 17-39) and migrated with synthetic hACTH
      (1-39) in a gel filtration system. This form also exhibited ACTH bioactivity in a
      dispersed rat adrenal cell bioassay system, with a mean immunoassay/bioassay
      ratio of 1.5. Gel filtration revealed multiple size classes of immunoreactive
      beta-endorphin; a major peak of radioreceptor activity was detected which
      exhibited a K(av) similar to that of authentic beta-endorphin. A major portion of
      immunoreactive beta-endorphin-sized material exhibited retention times similar to
      those of synthetic human and camel beta-endorphin upon reverse-phase high
      pressure liquid chromatography. These distinctive properties and specificities
      would seem to exclude the presence of limited homologies with sequences present
      in other proteins. High molecular weight material containing both ACTH and beta
      endorphin antigenic determinants was also demonstrated, suggesting, but not
      proving, the presence of a common precursor molecule.

PMID- 16593173
TI  - General phase-invariant formulas of higher order: Expected values.
AB  - Formulas for the cosines of the higher order phase invariants that arise in
      crystal structure analysis are derived as expected values from determinantal
      joint probability distributions. The values of the cosines of the invariants are
      expressed in terms of averages over simple functions of known structure factor
      magnitudes. The formulas are termed "general" to distinguish them from formulas
      that have more restricted averages and are termed "special." As with the special
      formulas, the best opportunity for obtaining useful information from these
      formulas is provided by embedded seminvariants formed from the invariants by use
      of relationships among the phases that arise from the space group symmetries.

PMID- 16593174
TI  - Evaluation of single-photon-counting measurements of excited-state lifetimes.
AB  - An extremely short instrumental response function for a single-photon-counting
      system has been obtained by using a low-jitter photomultiplier tube, fast
      amplification of the single photoelectron pulse from this photomultiplier, a
      constant fraction discriminator with a wide bandwidth input, and a stable
      reference timing signal. This synchronously mode-locked laser system has been
      shown to be capable of measuring the fluorescence lifetimes of compounds from 66
      psec to 4.5 nsec. The estimated error in these determinations is 6% or 10 psec,
      whichever is greater. This apparatus has proved itself to be superior to the
      previously used nitrogen flashlamp apparatus for the determination of
      subnanosecond lifetimes. The validity of using deconvolution to determine
      lifetimes shorter than the instrumental response function has been verified.

PMID- 16593175
TI  - Combined-information protein structure refinement: Potential energy-constrained
      real-space method for refinement with limited diffraction data.
AB  - A potential energy-constrained real-space refinement method designed for use with
      x-ray diffraction data of low to moderate resolution has been developed. The
      number of adjustable parameters is severely restricted to ensure a reasonable
      ratio of data to parameters. Only dihedral angles are allowed to vary; bond
      lengths and bond angles are fixed at physically reasonable values. The structure
      of bovine pancreatic trypsin inhibitor was refined by using this method with data
      to only 2.5-A resolution. Both the R-factor and the electron-density map improved
      throughout the refinement, and the final structure was a satisfactory
      approximation to the 1.5-A structure.

PMID- 16593176
TI  - Model for primary charge separation in reaction centers of photosynthetic
      bacteria.
AB  - We present model calculations of the dynamics of primary electron transfer (ET)
      in reaction centers of photosynthetic bacteria. We obtain half times of [unk]1 ps
      and approximately 5 ps for the first two ET processes, in excellent agreement
      with experimental observations. Our model is based on (i) a theoretical framework
      capable of describing ET in the presence of strong electronic interstate
      resonance coupling and (ii) energy parameters extracted from recent experimental
      data and molecular orbital calculations. Our analysis suggests that (i) strong
      electronic interstate mixing is crucial to the rapidity and efficiency of
      irreversible ET; (ii) possibly five rather than three electronic states
      participate in the transient ET prior to the reduction in vivo of the quinone
      complex; and (iii) conventional ET theories, which rely on weak electronic
      interstate mixing, are unfit for describing ET in reaction centers of
      photosynthetic bacteria.

PMID- 16593177
TI  - Characterizing harmonic immersions of surfaces with indefinite metric.
AB  - Harmonic maps X:(S,h) --> N from a 2-manifold S with indefinite metric h to a
      semi-Riemannian manifold N are characterized, assuming that the induced metric I
      is nondegenerate. Except in one very special case, the characterizations involve
      a canonically determined holomorphic quadratic differential on a naturally chosen
      conformal structure. This is surprising because the Euler-Lagrange equation that
      X must satisfy is basically the wave equation. The Gauss map of a spacelike or
      timelike surface in Minkowski 3-space is shown to be harmonic if and only if mean
      curvature is constant. Finally, it is noted that a harmonic map X:(S,h) --> N
      with indefinite h and nondegenerate I normally gives rise to a sine-Gordon, a
      sinh-Gordon, or a cosh-Gordon equation, provided that the intrinsic curvature of
      I is constant.

PMID- 16593178
TI  - Stochastic games have a value.
AB  - Undiscounted nonterminating stochastic games in which the state and action spaces
      are finite have a value.

PMID- 16593179
TI  - Crosslink precursors for the dipteran puparium.
AB  - During sclerotization of puparial proteins, tyrosine, lysine, and histidine were
      converted to highly basic aromatic metabolites. Peptides generated from the
      sclerotized cuticle with N-bromosuccinimide included the basic derivatives among
      the hydrolysis products. The absorbance maxima of the aromatic metabolites were
      25 nm lower than those of the conventional tyrosyl peptides, with phenolic
      character poorly expressed or absent. Post-translational modification of the
      structural proteins preceded visual expression of tanning because aromatic
      conjugates also were present prior to pupariation. These results are consistent
      with a crosslinking mechanism favoring covalent bonding between protein chains.

PMID- 16593180
TI  - Establishment of a cell line from lepidopteran wing imaginal discs: Induction of
      newly synthesized proteins by 20-hydroxyecdysone.
AB  - A cell line has been developed from the imaginal wing discs of the lepidopteran
      insect Trichoplusia ni (Hubner). The cells grow in suspension as fluid-filled,
      multicellular vesicles. The cell line has been designated IAL-TND1. Two
      dimensional electrophoresis (isoelectric focusing and sodium dodecyl
      sulfate/polyacrylamide gels) of [(35)S]methionine-labeled proteins revealed
      similar patterns for IAL-TND1 cells and whole T. ni wing imaginal discs.
      Additionally, exposure to the insect steroid hormone 20-hydroxyecdysone
      stimulated the synthesis of the same new proteins in both whole wing discs and
      IAL-TND1 cell vesicles.

PMID- 16593181
TI  - Prothoracic glands of the saturniid moth Samia cynthia ricini possess a circadian
      clock controlling gut purge timing.
AB  - In the moth Samia cynthia ricini, timing of the release of prothoracicotropic
      hormone is controlled by a circadian clock in the cephalic organ (brain); while
      this hormone release is necessary for gut purge, the final timing of this event
      is controlled by a circadian clock in the prothoracic glands that gates release
      of ecdysone. The photoreceptor of the prothoracic gland clock(s) is extraocular
      and evidently in the glands themselves. Demonstration that the clock and its
      photoreceptor are in the prothoracic glands is based on a mixture of localized
      illuminations and the transplantation of glands from one larva to another.

PMID- 16593182
TI  - Upper stratospheric photolysis of NaCl and KCl.
AB  - Sodium chloride has been postulated to be formed in the stratosphere by the
      reaction of NaOH with HCl, and an analogous reaction should occur also for KOH,
      with the formation of KCl. Photodissociation rates have been calculated for both
      NaCl and KCl using the published ultraviolet absorption cross sections below 300
      nm. Both molecules absorb strongly and have photodissociation lifetimes of only a
      few minutes in the upper stratosphere. Neither molecule is an effective sink for
      chlorine above an altitude of about 35 km.

PMID- 16593183
TI  - Prediction of the shapes of deformed nuclei by the polyspheron theory.
AB  - It is pointed out that some features of the shapes of (62) (154)Sm, (68) (166)Er,
      and (70) (176)Yb as reported by Cooper et al. [Cooper, T., Bertozzi, W.,
      Heisenberg, J., Kowalski, S., Turchinetz, W., Williamson, C., Cardman, L.,
      Fivozinsky, S., Lightbody, J., Jr., & Penner, S. (1976) Phys. Rev. C 13, 1083
      1094] from electron-scattering experiments agree reasonably well with the
      description of these nuclei, derived from the values of the rotational energy
      levels, as consisting of a large spherical part (essentially (132)Sn) and a cap
      [Pauling, L. (1969) Proc. Natl. Acad. Sci. USA 64, 807-809; Pauling, L. &
      Robinson, A. B. (1975) Can. J. Phys. 53, 1953-1964].

PMID- 16593184
TI  - Agrobacterium Ti plasmid indoleacetic acid gene is required for crown gall
      oncogenesis.
AB  - A gene (iaaP) necessary for virulence and indoleacetic acid (IAA) production has
      been located on a nopaline Ti plasmid of Agrobacterium tumefaciens C58. iaaP
      function was established by using transformation to insert nopaline or octopine
      Ti plasmids into an avirulent, Ti plasmid-free mutant 1D1293-3 that was defective
      in IAA synthesis (iaaC(-)). The resulting transformants produced increased levels
      of IAA and virulence was restored. When these transformants were cured of their
      Ti plasmid, virulence and high IAA production levels were concomitantly lost. A
      Tn5 mutagenized TiC58 plasmid, deficient in the ability to direct increased
      synthesis of IAA, was inserted by transformation into mutant 1D1293-3. The
      resulting transformants 1D1293-3 (TiC58::Tn5) remained avirulent and iaaP(-).
      Restriction analysis of the TiC58::Tn5 plasmid DNA identified the iaaP gene at
      20.9 kilobases to the left of the T-DNA. A major aromatic-amino-acid
      aminotransferase is coded by the iaaC gene, but not by the iaaP gene. The
      possible reasons for the iaaP locus to be situated outside the T-DNA region are
      discussed.

PMID- 16593185
TI  - F-actin in conifer roots.
AB  - The distribution of F-actin in the complex tissues of a higher plant organ has
      been visualized by fluorescence labeling the roots of the conifers Chamaecyparis
      obtusa and Pseudotsuga menziesii with F-actin-specific fluorescent dye-conjugated
      phallicidin. F-actin is present in the parenchymatous cells of the vascular
      tissue. Some vascular parenchyma cells possess larger numbers of F-actin
      containing structures (microfilament bundles) than are known to exist in any
      other higher plant cell. Tissue type appears to be an important determinant of
      the presence or absence of F-actin in a cell. For example, in contrast to
      vascular cells, cortical cells show no indication of fluorescence labeling of F
      actin after incubation with fluorescent phallicidin. Cytoplasmic streaming is
      seen only in vascular cells and in a pattern that reflects the intracellular
      distribution of F-actin.

PMID- 16593186
TI  - Optical properties of etiolated plant tissues.
AB  - Etiolated tissues of several plants are multiple bundles of fiber optics capable
      of coherent transfer of light over at least 20 mm. The acceptance angles (the
      angles at which light can be intercepted and then internally reflected
      longitudinally) for mung beans, oats, and corn are 47 degrees , 59 degrees , and
      52 degrees -54 degrees , respectively. The shapes of the curves that describe the
      acceptance angles are the same for various tissues of the same plant but differ
      between species. The pattern of light transmitted longitudinally through a tissue
      is dependent on the angle at which the light intercepts the side of the tissue
      and is strongly influenced by the tissue geometry. When 0.5 mm of the tip is
      irradiated, the amount of light traveling down the "shaded" side of the
      coleoptile is equal to or 2- to 3-fold greater than the amount traveling down the
      "lighted" side.

PMID- 16593187
TI  - In vivo recombination of cauliflower mosaic virus DNA.
AB  - LIGATION AND RECOMBINATION OF THE DNA OF CAULIFLOWER MOSAIC VIRUS (CAMV) IS
      DEMONSTRATED BY THE FOLLOWING EXPERIMENTS: (i) Ligation: Different noninfectious
      fragments of the CaMV genome (obtained after insertion into plasmid pBR322
      followed by enzymatic excision) regained infectivity when mixtures of them were
      used to inoculate their host. The symptom appearance was delayed by comparison
      with a typical CaMV infection, and only the newly formed leaves were affected.
      (ii) Recombination: Pairs of noninfectious recombinant full-length CaMV genomes
      (integrated into pBR322 at different restriction endonuclease sites) regained
      infectivity upon simultaneous inoculation of a sensitive host. The symptomatology
      of the resulting infection was indistinguishable from that of a typical CaMV
      infection. We show that progeny DNA had the same characteristics (size,
      structure, restriction endonuclease digestion pattern) as bona fide CaMV DNA, and
      that the vector pBR322 had been completely eliminated. A cloned tandem dimer of
      CaMV DNA with a partial deletion similarly was infectious in the plant assays.
      This system should be useful to study the expression of mutant genomes, thus
      allowing characterization of the CaMV genes.

PMID- 16593188
TI  - cDNA cloning and induction of the alcohol dehydrogenase gene (Adh1) of maize.
AB  - cDNA clones of Adh1, one of two genes encoding alcohol dehydrogenase (ADH;
      alcohol:NAD(+) oxidoreductase, EC 1.1.1.1) in the maize genome, have been
      isolated. They were derived from mRNA extracted from anaerobically treated roots
      of maize seedlings. Identification was initially made on the basis of molecular
      weight and electrophoretic properties of the in vitro polypeptide obtained in
      hybridization-release-translation experiments. The identification was confirmed
      by antibody precipitation and by the use of maize stocks having different genetic
      constitutions at the Adh1 locus. The sequence of the longest cDNA segment,
      approximately 900 base pairs, was determined and appears to code for 168 COOH
      terminal amino acids and to have a 3' nontranslated region of 364 base pairs.
      Reverse Southern hybridizations established that two different Adh1-S stocks
      produce a mRNA of 1,650 nucleotides, whereas an additional mRNA of 1,750
      nucleotides is produced in three Adh1-F stocks. A 50-fold increase in Adh1 mRNA
      level occurs during anaerobiosis, reaching a maximum at 5 hr. Return to aerobic
      conditions indicates a half-life of more than 18 hr for the anaerobically induced
      Adh1 mRNA.

PMID- 16593189
TI  - Characterization of external electric field-driven ATP synthesis in chloroplasts.
AB  - External electric field-induced ADP phosphorylation (EFP) in lettuce chloroplasts
      was monitored with a coupled luciferin-luciferase enzymatic assay. This assay
      made it possible to follow ATP synthesis in a kinetically competent manner. The
      EFP reaction was found to be a much slower process than the light-driven reaction
      in the same system. The amount of ATP synthesized after a single electric field
      pulse corresponds to many turnovers of the ATP synthase.

PMID- 16593191
TI  - On 1/f noise and other distributions with long tails.
AB  - It is shown, following Shockley [Shockley, W. (1957) Proc. IRE 45, 279-290],
      that, when a population is engaged in tasks whose completion requires the
      successful conclusion of many independent subtasks, the distribution function for
      successes in the primary task is log normal. It is also shown that, when the
      dispersion of the log-normal distribution is large, the distribution is mimicked
      by a 1/x distribution over a wide range of x. This argument provides a generic
      set of processes that yields the much observed 1/x distribution, and will also
      lead to a 1/f noise spectrum. It is commonly found that distributions that seem
      to be log normal over a broad range (say to the 95th percentile of a population)
      change to an inverse fractional power (Pareto) distribution for the last few
      percentile. Annual income distributions are examples with this structure. The
      very wealthy generally achieve their superwealth through amplification processes
      that are not available to most. We have introduced a simple amplification model
      to characterize the transition from a log-normal distribution to an inverse-power
      Pareto tail.

PMID- 16593190
TI  - Tumor induction by Agrobacterium rhizogenes involves the transfer of plasmid DNA
      to the plant genome.
AB  - The DNA from tumors of Nicotiana glauca initiated by strains of Agrobacterium
      rhizogenes was shown to contain sequences that are homologous to the root
      inducing (Ri) plasmid of the bacterium. Two independently established tumor lines
      contained a similar portion of the Ri-plasmid. The Ri-plasmid also hybridized to
      DNA fragments from uninfected N. glauca. A cosmid clone of the Ri-plasmid
      encompassing the region containing the Ri-plasmid sequences that are stably
      transferred to the plant also hybridized to the Ri-plasmid-related fragments
      found in uninfected plants. Five of six tumor lines tested produced a tumor
      specific compound that is similar to agropine.

PMID- 16593192
TI  - Periodic explosions by positive feedback in a rising foam column.
AB  - An aqueous foam rising adiabatically in a column suffers a drop in temperature.
      Under appropriate conditions, such a column periodically explodes. We here trace
      this explosion to the tight thermal coupling between the foam and its enclosing
      glass column. When the surface surfactant concentration is unbuffered by
      micelles, a positive feedback exists between the flow of heat from the walls into
      the foam and the thermal conductivity of the foam itself. In our highly expanded
      foam, heat is conducted through the foam cells' interior primarily by the heat
      pipe effect. Such an effect is retarded by a dense layer of surfactant molecules.
      Heat absorption causes cell expansion, which, in a foam unbuffered by micelles,
      causes a reduction in surface concentration of surfactant molecules and, hence,
      in an increase in thermal conductivity. This interpretation of our observed
      periodic explosions is in agreement with all of our observations.

PMID- 16593193
TI  - Temperature dependence of the reduction potential of blue copper in fungal
      laccase.
AB  - Thin-layer spectroelectrochemical methods have been employed to measure the
      reduction potentials of the blue copper in Polyporus versicolor laccase (EC
      1.10.3.2) between 7 degrees C and 41 degrees C (0.2 M sodium phosphate, pH 5.4).
      Thermodynamic parameters are: DeltaS degrees = -13.9 +/- 2 cal/mol-K; DeltaH
      degrees = -22.1 +/- 0.5 kcal/mol; E degrees (25 degrees C) = 780 +/- 3 mV vs. the
      normal hydrogen electrode. Comparison of the DeltaS degrees and DeltaH degrees
      values with those for single-site proteins suggests that the high potential of
      the blue copper in fungal laccase is attributable mainly to stabilization of the
      copper (I) center by enhanced ligand binding interactions and that protein
      solvation effects play a lesser role.

PMID- 16593194
TI  - Immersions of manifolds.
AB  - This paper outlines a proof of the conjecture that every compact, differentiable,
      n-dimensional manifold immerses in Euclidean space of dimension 2n - alpha(n),
      where alpha(n) is the number of ones in the dyadic expansion of n.

PMID- 16593195
TI  - Sterol patterns of cultured zooxanthellae isolated from marine invertebrates:
      Synthesis of gorgosterol and 23-desmethylgorgosterol by aposymbiotic algae.
AB  - QUANTITATIVE STEROL COMPOSITIONS OF CULTURED ZOOXANTHELLAE ISOLATED FROM VARIOUS
      PACIFIC AND ATLANTIC INVERTEBRATE HOSTS: Zoanthus sociatus (a zoanthid), Oculina
      diffusa (a scleractian coral), Tridacna gigas (a giant clam), Melibe pilosa (a
      nudibranch), and Aiptasia pulchella (a sea anemone) are reported. The results
      clearly demonstrate large differences in sterol patterns of zooxanthellae and
      that there is no obvious relationship between the taxonomic affiliation of the
      host and the sterol pattern of its isolated symbiont. The sterols of the
      zooxanthellae of O. diffusa (Cnidaria) and T. gigas (Mollusca) are qualitatively
      equivalent. Based on the structures of the two major free sterols synthesized by
      each alga, the zooxanthellae from different hosts were separated into three
      distinct groups. It was also found that an aposymbiotic alga can synthesize the
      unique marine sterols gorgosterol and 23-desmethylgorgosterol. Most of the
      sterols were identified by using mass spectroscopy and 360-MHz proton magnetic
      resonance. Spectroscopic data are reported for four novel sterols-(23,24R)
      dimethyl-5alpha-cholest-(22E)-en-3beta-o l, 23-methyl-5alpha-cholest-22E-en-3beta
      ol, cholesta-5,14-dien-3beta-ol, and 4alpha-methyl-5alpha-cholesta-8(14)-24-dien
      3beta-ol.

PMID- 16593196
TI  - Cycloartenol-derived sterol biosynthesis in the Peronosporales.
AB  - Selected species of the order Peronosporales, which are unable to epoxidize
      squalene and thus synthesize sterols, are able to metabolize exogenous
      cycloartenol to lanosterol and in some organisms to fucosterol, ergosterol, and
      cholesterol. Lanosterol was less effectively utilized but some ergosterol and
      cholesterol were yielded. Fucosterol was very efficiently metabolized by most
      species to ergosterol, Delta(7)-ergostenol, Delta(5)-ergostenol, cholestanol, and
      cholesterol. Several unknown sterols were observed in most trials. These data
      suggest a vestigial sterol synthetic pathway derived from cycloartenol, followed
      by possible isomerization to lanosterol and then to other sterols.

PMID- 16593197
TI  - Responses of corn root protoplasts to exogenous reduced nicotinamide adenine
      dinucleotide: Oxygen consumption, ion uptake, and membrane potential.
AB  - Addition of 1.5 mM NADH tripled the O(2) consumption in corn root protoplasts.
      The stimulation was temperature and pH dependent, specific to NADH, and
      accompanied by a 2- to 3-fold increase in K(+) and P(i) uptake into protoplasts.
      The increase in ion uptake was not due to the accumulation of NADH into
      protoplasts. The effect of exogenous NADH on O(2) consumption and ion uptake was
      also evident in corn root segments but to a lesser extent. A 20-mV
      hyperpolarization of protoplast membrane potential occurred on addition of NADH
      and was abolished by the uncoupler carbonyl cyanide p
      trifluoromethoxyphenylhydrazone. Increases in cell volume of 30% and 40% were
      detected in response to NADH/H(+) and NADH/H(+)/K(+), respectively. The data are
      discussed in terms of a transmembrane redox reaction and the possibility that
      some part of the energy-linked ion transport may be driven by a NADH --> O(2)
      electron-transport system in the plasmalemma.

PMID- 16593198
TI  - Viruses of symbiotic Chlorella-like algae isolated from Paramecium bursaria and
      Hydra viridis.
AB  - We previously reported that isolation of symbiotic Chlorella-like algae from the
      Florida strain of Hydra viridis induced replication of a virus (designated HVCV
      1) in the algae. We now report that isolation of symbiotic Chlorella-like algae
      from four other sources of green hydra and one source of the protozoan Paramecium
      bursaria also induced virus synthesis. Algae from one of these hydra contained a
      virus identical to HVCV-1 (based on its rate of sedimentation, buoyant density,
      reaction to HVCV-1 antiserum, and DNA restriction fragments) whereas algae from
      the other three hydra contained another similar, but distinct, virus (designated
      HVCV-2). The virus from the paramecium algae (designated PBCV-1) was distinct
      from both HVCV-1 and HVCV-2. The symbiotic algae in the hydra could also be
      distinguished ultrastructurally. Chloroplasts of both algae that produced HVCV-1
      lacked a pyrenoid whereas chloroplasts of the other three symbiotic algae
      contained pyrenoids. Since all symbiotic eukaryotic algae we have examined have
      had virus, a potential viral role in symbiosis is suggested.

PMID- 16593199
TI  - Statistical hydromechanics of the solar differential rotation.
AB  - An axisymmetric hydrodynamic model of the solar differential rotation is
      suggested that differs from the previous axisymmetric models (with arbitrarily
      given anisotropic viscosity) in the use of the hydrodynamic equations (the
      Friedmann-Keller equations) for the statistical second moments of the
      fluctuations of velocity and entropy-i.e., turbulent fluxes of momentum and
      entropy. The model gives a correct reproduction of the differential rotation
      (without unreal temperature differences on the Sun's surface peculiear to the
      anisotropic viscosity models) and makes possible calculations of the second
      moments.

PMID- 16593200
TI  - On the dynamical basis of the classification of normal galaxies.
AB  - Some realistic galaxy models have been found to support discrete unstable spiral
      modes. Here, through the study of the relevant physical mechanisms and an
      extensive numerical investigation of the properties of the dominant modes in a
      wide class of galactic equilibria, we show how spiral structures are excited with
      different morphological features, depending on the properties of the equilibrium
      model. We identify the basic dynamical parameters and mechanisms and compare the
      resulting morphology of spiral modes with the actual classification of galaxies.
      The present study suggests a dynamical basis for the transition among various
      types and subclasses of normal and barred spiral galaxies.

PMID- 16593201
TI  - Spatial homogeneity and redshift-distance laws.
AB  - Spatial homogeneity in the radial direction of low-redshift galaxies is subjected
      to Kafka-Schmidt V/V(m) tests using well-documented samples. Homogeneity is
      consistent with the assumption of the Lundmark (quadratic redshift-distance) law,
      but large deviations from homogeneity are implied by the assumption of the Hubble
      (linear redshift-distance) law. These deviations are similar to what would be
      expected on the basis of the Lundmark law. Luminosity functions are obtained for
      each law by a nonparametric statistically optimal method that removes the
      observational cutoff bias in complete samples. Although the Hubble law
      correlation of absolute magnitude with redshift is reduced considerably by
      elimination of the bias, computer simulations show that its bias-free value is
      nevertheless at a satistically quite significant level, indicating the self
      inconsistency of the law. The corresponding Lundmark law correlations are quite
      satisfactory satistically. The regression of redshift on magnitude also involves
      radial spatial homogeneity and, according to R. Soneira, has slope determining
      the redshift-magnitude exponent independently of the luminosity function. We
      have, however, rigorously proved the material dependence of the regression on
      this function and here exemplify our treatment by using the bias-free functions
      indicated, with results consistent with the foregoing argument.

PMID- 16593202
TI  - Theory of periodic structures in lipid bilayer membranes.
AB  - An approximate, new model for the structure of the periodic, undulated P(beta'),
      phase of phosphatidylcholine bilayers is proposed. The properties of this phase
      are deduced by minimizing a Landau-de Gennes expression for the bilayer free
      energy when this free energy contains a term favoring a spontaneous curvature of
      the membrane. The theoretical calculation leads to a model for the P(beta') phase
      of phosphatidylcholine bilayers having a number of novel physical properties,
      including periodic variations in membrane "fluidity."

PMID- 16593203
TI  - Ab initio calculations of dilithiopropenes.
AB  - Ab initio molecular orbital calculations with the 3-21G basis set show the most
      stable dilithiopropene structure to be the di-pi lithium-bridged structure VI of
      1,3-dilithiopropene. This structure is most simply regarded as an ion triplet of
      two lithium cations and a propenylidene dianion.

PMID- 16593204
TI  - Photosensitized production of hydrogen by hydrogenase in reversed micelles.
AB  - Hydrogenase (hydrogen:ferricytochrome c(3) oxidoreductase, EC 1.12.2.1) from
      Desulfovibrio vulgaris was encapsulated in reversed micelles with
      cetyltrimethylammonium bromide as surfactant and a chloroform/octane mixture as
      solvent. Reducing equivalents for hydrogenase-catalyzed hydrogen production were
      provided by vectorial photosensitized electron transfer from a donor (thiophenol)
      in the organic phase through a surfactant-Ru(2+) sensitizer located in the
      interphase to methyl viologen concentrated in the aqueous core of the reversed
      micelle. The results show that reversed micelles provide a microenvironment that
      (i) stabilizes hydrogenase against inactivation and (ii) allows an efficient
      vectorial photosensitized electron and proton flow from the organic phase to
      hydrogenase in the aqueous phase.

PMID- 16593205
TI  - Examples of constant mean curvature immersions of the 3-sphere into euclidean 4
      space.
AB  - Mean curvature is one of the simplest and most basic of local differential
      geometric invariants. Therefore, closed hypersurfaces of constant mean curvature
      in euclidean spaces of high dimension are basic objects of fundamental importance
      in global differential geometry. Before the examples of this paper, the only
      known example was the obvious one of the round sphere. Indeed, the theorems of H.
      Hopf (for immersion of S(2) into E(3)) and A. D. Alexandrov (for imbedded
      hypersurfaces of E(n)) have gone a long way toward characterizing the round
      sphere as the only example of a closed hypersurface of constant mean curvature
      with some added assumptions. Examples of this paper seem surprising and are
      constructed in the framework of equivariant differential geometry.

PMID- 16593206
TI  - Lower bounds for the life-span of solutions of nonlinear wave equations in three
      dimensions.
AB  - The paper deals with strict solutions u(x,t) = u(x(1),x(2),x(3),t) of an equation
      [Formula: see text] where Du is the set of four first derivatives of u. For given
      initial values u(x,0) = epsilonF(x), u(t)(x,0) = epsilonG(x), the life span
      T(epsilon) is defined as the supremum of all t to which the local solution can be
      extended for all x. Blowup in finite time corresponds to T(epsilon) < infinity.
      Examples show that this can occur for arbitrarily small epsilon. On the other
      hand, T(epsilon) must at least be very large for small epsilon. By assuming that
      a(ik),F,G [unk] C(infinity), that a(ik)(0) = 0, and that F,G have compact
      support, it is shown that [Formula: see text] for every N. This result had been
      established previously only for N < 4.

PMID- 16593208
TI  - Fluvial processes and local lithology controlling abundance, structure, and
      composition of mussel beds.
AB  - In the Salmon River Canyon, Idaho, the fresh-water pearl mussel, Margaritifera
      falcata, attains maximum density and age in river reaches where large block
      boulders structurally stabilize cobbles and interstitial gravels. We hypothesize
      that block-boulders prevent significant bed scour during major floods, and these
      boulder-sheltered mussel beds, although rare, may be critical for population
      recruitment elsewhere within the river, especially after periodic flood scour of
      less protected mussel habitat. Mussel shells in Indian middens adjacent to these
      boulder-stabilized areas suggest that prehistoric tribes selectively exploited
      the high-density old-aged mussel beds. Locally, canyon reaches are aggrading with
      sand and gravel, and M. falcata is being replaced by Gonidea angulata.

PMID- 16593207
TI  - Ethylene regulation of gene expression in carrots.
AB  - The respiration of carrot (Daucus carota L.) roots is stimulated by ethylene.
      Polyribosomes were shown to proliferate concomitantly with the increase in
      respiration, and the extent of polyribosome augmentation was closely correlated
      to the amount of respiratory stimulation. In addition to the increase in
      quantity, ethylene caused a 2-fold increase in the average polyribosome size,
      suggesting tighter packing of ribosomes on RNA. In vitro translation of carrot
      polyadenylylated RNA with the rabbit reticulocyte lysate system followed by
      electrophoresis of the resulting translation products showed that ethylene
      treatment results in the appearance of new mRNAs.

PMID- 16593210
TI  - Evidence for a respiratory chain in the chloroplast.
AB  - Evidence is given for the existence of an electron transport pathway to oxygen in
      the thylakoid membranes of chloroplasts (chlororespiration). Plastoquinone is
      shown to be a redox carrier common to both photosynthetic and chlororespiratory
      pathways. It is shown that, in dark-adapted chloroplasts, an electrochemical
      gradient is built up across the thylakoid membrane by transfer of electrons
      through the chlororespiratory chain as well as by reverse functioning of the
      chloroplast ATPases. It is proposed that these mechanisms ensure recycling of the
      ATP and NAD(P)H generated by the glycolytic pathway converting starch into triose
      phosphates. Chlororespiration is thus an O(2)-uptake process distinct from
      photorespiration and the Mehler reaction. The evolutionary significance of
      chlororespiration is discussed.

PMID- 16593209
TI  - A special fructose bisphosphate functions as a cytoplasmic regulatory metabolite
      in green leaves.
AB  - Fructose 2,6-bisphosphate (Fru-2,6-P(2)), a regulatory metabolite discovered in
      animal cells and recently reported to occur in etiolated seedlings, was found to
      be present in the cytoplasmic fraction of leaves of spinach and peas (typical
      C(3) plants, in which a three-carbon carboxylic acid is a major early
      photosynthetic product). At concentrations approximating those calculated to
      occur physiologically, Fru-2,6-P(2) modulated two enzymes of the leaf cytoplasm:
      (i) Fructose-1,6-bisphosphatase (EC 3.1.3.11), a key enzyme of sugar synthesis,
      was competitively inhibited by Fru-2,6-P(2), and (ii) pyrophosphate-linked
      phosphofructokinase (inorganic pyrophosphate-D-fructose-6-phosphate 1
      phosphotransferase, EC 2.7.1.90), a cytoplasmic enzyme that now seems important
      in glycolysis of C(3) plants, was activated by Fru-2,6-P(2). There was no
      indication of a role for Fru-2,6-P(2) in photosynthesis of either chloroplasts or
      oxygenic prokaryotes. The results suggest that Fru-2,6-P(2) functions in the
      regulation of glycolysis and gluconeogenesis (carbohydrate synthesis) in the
      cytoplasm of leaves of C(3) plants.

PMID- 16593211
TI  - The bee's map of the e-vector pattern in the sky.
AB  - It has long been known that bees can use the pattern of polarized light in the
      sky as a compass cue even if they can see only a small part of the whole pattern.
      How they solve this problem has remained enigmatic. Here we show that the bees
      rely on a generalized celestial map that is used invariably throughout the day.
      We reconstruct this map by analyzing the navigation errors made by bees to which
      single e-vectors are displayed. In addition, we demonstrate how the bee's
      celestial map can be derived from the e-vector patterns in the sky.

PMID- 16593212
TI  - Fractal dimensionality of Levy processes.
AB  - We determine the fractal dimensionality D of the trajectories of a class of
      translationally invariant Markov processes. We also provide two simple
      operational measures to estimate D.

PMID- 16593213
TI  - Two-fluid theory and thermodynamic properties of liquid mixtures: General theory.
AB  - The two-fluid theory of binary mixtures postulates that the extensive
      thermodynamic properties of a binary mixture may be expressed by the
      contributions of two hypothetical fluids that mix ideally. This postulate,
      coupled with an expression for the partition function of the hypothetical fluid,
      permits evaluation of the properties of binary liquid mixtures by using only two
      adjustable binary parameters. Particular attention is given to the problem of
      nonrandomness in mixtures. A quantitative description of nonrandomness is
      achieved by combining the two-fluid concept with a hypothesis for ensemble
      averaging of a distribution of nearest-neighbor pairs.

PMID- 16593214
TI  - Treatment of disordered and ordered systems of polymer chains by lattice methods.
AB  - Classical lattice theories of systems of long-chain molecules provide estimates
      of the number Z of random configurations to the exclusion of ordered ones. The
      decrease of Z thus estimated to values [unk]1 with decrease in chain flexibility
      at high densities is genuine, but it does not take account of eligible ordered
      configurations; the latter are not a subset of the configurations whose numbers
      are estimated by classical lattice methods. Failure to recognize this fact and
      the fundamental distinction between disordered and ordered states has engendered
      misinterpretations and has cast doubt on the validity of lattice-statistical
      methods. In a system at equilibrium, the decline of Z (disordered) with decrease
      in chain flexibility must be arrested by a first order transition to an ordered
      state. The inference that approach of Z (disordered) to values <1 presages a
      thermodynamic transition of second order is tenable only if the array of ordered
      configurations, not comprehended by theories in which the mean field of
      unoccupied lattice sites is random, can be ignored.

PMID- 16593215
TI  - Random walk properties from lattice bond enumeration: Steady-state diffusion on
      two- and three-dimensional lattices with traps.
AB  - We have applied the lattice bond enumeration method to the calculation of the
      steady-state diffusion in a lattice with fixed traps. We show that, to first
      order in density of traps, our random walk calculations for the effective
      diffusion constant in lattices with periodically arrayed traps are in exact
      agreement with calculations carried out previously for randomly arrayed traps
      embedded in a three-dimensional continuum medium (fluid). Our lattice random walk
      results are independent of dimension for d > 1, and we conjecture that this is
      also true for the continuum diffusion model.

PMID- 16593216
TI  - Conformation of cyclo(-L-Pro-Gly-)(3) and its Ca and Mg complexes.
AB  - The synthetic hexapeptide cyclo(-L-Pro-Gly-)(3) is an ionophore that shows
      interesting conformational changes upon binding metal ions. X-ray
      crystallographic studies of this peptide show that when it is crystallized from
      an ethanol/ethyl acetate mixture the ring takes up an asymmetric conformation
      containing one cis peptide bond. In crystals of a Ca(2+) complex, the cation is
      sandwiched between two peptide molecules that differ markedly in conformation.
      However, both exhibit threefold symmetric forms, with all six peptide bonds in
      the molecule occurring in the usual trans conformation. The Ca(2+) is
      octahedrally surrounded by six glycyl carbonyl oxygens from the two peptides at
      an average distance of 2.26 A and can easily be released by the disruption of the
      peptide sandwich. In the magnesium complex, the peptide forms a 1:1 complex with
      the ion. The Mg(2+) is octahedrally coordinated to three glycyl carbonyls and
      three water oxygens. The average coordination distance between magnesium and the
      peptide oxygens is 2.03 A and that between magnesium and water oxygen is 2.11 A.
      The two peptide molecules in the asymmetric unit have similar conformations and
      have approximate threefold symmetry.

PMID- 16593217
TI  - A remark on minimal hypercones.
AB  - Let M be a minimal hypersurface in the sphere. It is shown that if the cone over
      M is a stable critical point for the area functional, then M admits a conformally
      equivalent metric with positive scalar curvature. This gives both topological and
      geometric restrictions on such hypersurfaces M.

PMID- 16593218
TI  - Microscale nutrient patches produced by zooplankton.
AB  - Both track autoradiography and grain-density autoradiography show that individual
      zooplankton create miniature patches of dissolved nutrients and that algae
      exploit those regions to absorb phosphate. The patches are short lived and can be
      dispersed artificially by small-scale turbulence. Our data support a simple model
      of encounters between algae and nutrient plumes produced by swimming zooplankton.

PMID- 16593219
TI  - Chloroplast DNA evolution and phylogenetic relationships in Lycopersicon.
AB  - Chloroplast DNA was purified from 12 accessions that represent most of the
      species diversity in the genus Lycopersicon (family Solanaceae) and from 3
      closely related species in the genus Solanum. Fragment patterns produced by
      digestion of these DNAs with 25 different restriction endonucleases were analyzed
      by agarose gel electrophoresis. In all 15 DNAs, a total of only 39 restriction
      site mutations were detected among 484 restriction sites surveyed, representing
      2,800 base pairs of sequence information. This low rate of base sequence change
      is paralleled by an extremely low rate of convergent change in restriction sites;
      only 1 of the 39 mutations appears to have occurred independently in two
      different lineages. Parsimony analysis of shared mutations has allowed the
      construction of a maternal phylogeny for the 15 accessions. This phylogeny is
      generally consistent with relationships based on morphology and crossability but
      provides more detailed resolution at several places. All accessions within
      Lycopersicon form a coherent group, with two of the three species of Solanum as
      outside reference points. Chloroplast DNA analysis places S. pennellii firmly
      within Lycopersicon, confirming recent studies that have removed it from Solanum.
      Red-orange fruit color is shown to be a monophyletic trait in three species of
      Lycopersicon, including the cultivated tomato, L. esculentum. Analysis of six
      accessions within L. peruvianum reveals a limited amount of intraspecific
      polymorphism which, however, encompasses all the variation observed in L.
      chilense and L. chmielewskii. It is suggested that these latter two accessions be
      relegated to positions within the L. peruvianum complex.

PMID- 16593220
TI  - Two-fluid theory and thermodynamic properties of liquid mixtures. Application to
      hard-sphere mixtures.
AB  - This paper is the second of three describing a two-fluid theory of binary liquid
      mixtures. The general theory presented in the preceding paper is used to derive a
      model for calculating thermodynamic properties of hard-sphere mixtures.
      Calculations indicate that desirable boundary conditions are satisfied.

PMID- 16593221
TI  - Environmental influences on the photooxidation of manganese by a zinc porphyrin
      sensitizer.
AB  - The photosensitized oxidation of a membrane-bound Mn(III) tetrapyridylporphyrin
      derivative by a Zn tetrapyridylporphyrin derivative, which is confined to the
      membrane, has been achieved in negatively charged membranes consisting of
      phosphatidylglycerol or phosphatidic acid. At the same time, the zwitterionic
      electron acceptor, propylviologen sulfonate (PVS(0)), is reduced in the aqueous
      phase. The same reaction cannot be obtained with zwitterionic or cationic
      membranes, nor does this photosensitized reaction take place in a homogeneous
      solution with Mn(III) tetrapyridylporphyrin and Zn tetrapyridylporphyrin. These
      results show that the organization of donor, sensitizer, and acceptor at an
      appropriately selected interface allows reactions that would not occur in
      homogeneous solutions.

PMID- 16593222
TI  - Native phytochrome: Inhibition of proteolysis yields a homogeneous monomer of 124
      kilodaltons from Avena.
AB  - Phytochrome purified from Avena as the red-absorbing form, Pr, by an established
      immunoaffinity column procedure is heterogeneous. Two major polypeptides and one
      minor polypeptide with apparent molecular masses of 118, 114, and 112 kilodaltons
      (kDal), respectively, are observed on NaDodSO(4)/polyacrylamide gel
      electrophoresis. In contrast, only a single band of 124 kDal is obtained when
      phytochrome is rapidly immunoprecipitated after extraction either (i) as the far
      red absorbing form, Pfr, in detergent-free buffer or (ii) in either spectral form
      in a 100 degrees C NaDodSO(4)-containing buffer. On two-dimensional gel
      electrophoresis the three column-purified species have pIs of 5.8, 6.0, and 6.0,
      whereas 124-kDal phytochrome is a single spot with a pI of 5.9. Incubation as Pr
      in extracts causes progressive conversion of the 124-kDal polypeptide to the 118-
      and 114-kDal species. This process is inhibited by phenylmethylsulfonyl fluoride,
      suggesting that Pr is susceptible and Pfr resistant to limited proteolysis during
      extraction. These data, and the fact that the cell-free translation product of
      phytochrome mRNA is also 124 kDal [Bolton, G. W. & Quail, P. H. (1982) Planta, in
      press], indicate that the native monomer from Avena is a single species of 124
      kDal. Thus the heterogeneous preparations of slightly lower molecular weight
      ("large" or "120-kilodalton" phytochrome) previously extensively characterized
      appear to have consisted of a mixture of partially degraded molecules that have
      undergone limited proteolysis during purification as Pr, as is established
      practice. A reexamination of the molecular properties of phytochrome appears
      necessary.

PMID- 16593223
TI  - Formation of hybrid phycobilisomes by association of phycobiliproteins from
      Nostoc and Fremyella.
AB  - Formation of phycobilisomes has been accomplished in vitro from isolated
      phycobiliprotein fractions obtained from the same blue-green alga (intrageneric)
      and from different blue-green algae (intergeneric). Phycobilisomes, which are
      supra-molecular complexes of phycobiliproteins, serve as major light-harvesting
      antennae for photosynthesis in blue-green and red algae. Intrageneric association
      into energetically functional phycobilisomes, previously reported to occur with
      Nostoc sp. allophycocyanin and phycoerythrin-phycocyanin complexes [Canaani, O.,
      Lipschultz, C. A. & Gantt, E. (1980) FEBS Lett. 115, 225-229], has been obtained
      with Fremyella diplosiphon. By their spectral properties (absorption,
      fluorescence excitation, and emission) and electron microscopic images, the
      native and in vitro-associated phycobilisomes were virtually indistinguishable.
      Intergeneric phycobilisomes have been produced from allophycocyanin of Nostoc sp.
      strain Mac. and phycoerythrin-phycocyanin of F. diplosiphon, as well as from the
      reverse mixtures. The yield of intergeneric phycobilisomes, favored by higher
      phycobiliprotein content in 0.75 M phosphate, pH 7.0/2.0 M sucrose, was 40-60%.
      Energy transfer to the terminal long-wavelength-emitting allophycocyanin in the
      phycobilisomes was evident from the 670-675 nm fluorescence emission peaks.
      Furthermore, excitation spectra showed the contribution of the respective
      phycoerythrins (Fremyella, lambda(max) 570; Nostoc, lambda(max) 573 and 553 nm),
      as well as that of phycocyanin and short-wavelength-absorbing allophycocyanin.
      Phycobilisomes of Nostoc and Fremyella, analyzed by NaDodSO(4)/polyacrylamide gel
      electrophoresis, possessed a number of polypeptides having similar molecular
      weights: the usual alpha- and beta-phycobilin-containing polypeptides of M(r)
      15,000-22,000, a faint band at M(r)ca. 95,000, and a prominent band at M(r)ca.
      31,000. The M(r) 31,000 polypeptide is assumed to provide the recognition site
      for attachment of the phycoerythrin-phycocyanin complexes with the
      allophycocyanin core. In vitro association was not obtained between
      allophycocyanin from Nostoc and phycoerythrin-phycocyanin complexes from
      Phormidium persicinum or Porphyridium sordidum.

PMID- 16593224
TI  - Requirement for a membrane potential for cellulose synthesis in intact cells of
      Acetobacter xylinum.
AB  - The marked lability in cell-free preparations of the enzyme system involved in
      cellulose biosynthesis in most organisms studied led us to investigate factors
      responsible for loss of activity on cellular disruption. Previous studies have
      led to the suggestion that the existence of a transmembrane electrical potential
      (DeltaPsi) may be one factor responsible for maintaining an active system in
      intact cells. In this report, we show that dissipation of the DeltaPsi in
      metabolizing cells of Acetobacter xylinum results in severe inhibition of
      cellulose synthesis. The effect can be reversed by restoration of the DeltaPsi.
      Inhibition of cellulose biosynthesis by dissipation of the DeltaPsi can be
      observed under conditions in which no substantial impairment of energy metabolism
      occurs-i.e., under conditions in which a transmembrane pH gradient is of
      sufficient magnitude to maintain an adequate overall protonmotive force across
      the membrane. The inhibition of cellulose biosynthesis is specifically related to
      changes in the DeltaPsi, since the process can proceed normally in the absence of
      the pH gradient. These results support the suggestion that loss of the DeltaPsi
      on cellular disruption may be one of the factors responsible for the low capacity
      for cellulose synthesis in isolated membrane preparations and also raise the
      possibility that modulation of the DeltaPsi could be one means of regulating the
      rate of cellulose synthesis in vivo.

PMID- 16593225
TI  - Reconstruction of the chloroplast noncyclic electron transport pathway from water
      to NADP with three integral protein complexes.
AB  - RECONSTRUCTION OF PHOTOSYNTHETIC NONCYCLIC ELECTRON TRANSPORT FROM WATER TO NADP
      HAS BEEN ACCOMPLISHED BY USING THREE INTEGRAL PROTEIN COMPLEXES ISOLATED FROM
      CHLOROPLAST THYLAKOID MEMBRANES: photosystems I and II and the cytochrome b(6)-f
      complex. This system shows an absolute dependence on the presence of all three
      protein complexes for NADP reduction, in addition to plastocyanin, ferredoxin,
      and ferredoxin-NADP reductase. The reconstructed system was found to be sensitive
      to low concentrations of known inhibitors of noncyclic electron transport.
      Depletion of the Rieske iron-sulfur center and bound plastoquinone from the
      cytochrome b(6)-f complex resulted in an inhibition of the photoreduction of
      NADP.

PMID- 16593226
TI  - Magnetic characterization of the primary state of bacterial photosynthesis.
AB  - The results of reaction yield-detected magnetic resonance (RYDMR) experiments
      carried out on modified bacterial photosynthetic reaction centers (RCs) are
      interpreted in terms of a model that assigns the initial charge-separated radical
      ion-pair state, P(F), as the carrier of the spectrum. The radical pair theory,
      which has been invoked to explain magnetic field effects in RCs, was
      significantly expanded to take into consideration the electron dipole-dipole
      interaction. It is shown that this is the largest interaction between the
      components of the radical ion pair. Quantum statistical calculations are
      described simulating the RYDMR spectra and low-field effects in quinone-depleted
      RCs. The experimental data on which the simulations are based are (i) the
      magnitude of the field effect at 3,000 G, (ii) the field at which 0.5 of the
      maximal field effect is observed, (iii) the P(F) population as a function of time
      at zero magnetic field, (iv) the RYDMR linewidth for low microwave field
      strength, (v) the RYDMR intensity and width as a function of microwave field, and
      (vi) the maximum RYDMR intensity at H(I) approximately 2J. With this information
      it was found possible to characterize P(F) in terms of four parameters, two
      containing structural information and two with kinetic implications. These are
      the dipole-dipole interaction, D = -47 +/- 10 x 10(-4) cm(-1); the exchange
      interaction, J = -7.5 +/- 1.9 x 10(-4) cm(-1); and the inverse rate constants of
      the decay of the radical pair states with singlet and triplet spin functions,
      respectively, k(S) (-1) = 15 +/- 4 nsec and k(T) (-1) = 1.8 +/- 0.2 nsec. The
      structural and dynamic implications of these parameters are discussed.

PMID- 16593227
TI  - A M(r) 95,000 polypeptide in Porphyridium cruentum phycobilisomes and thylakoids:
      Possible function in linkage of phycobilisomes to thylakoids and in energy
      transfer.
AB  - Two pigmented polypeptides with the same molecular weight (M(r) 95,000) were
      isolated from the photosynthetic apparatus of Porphyridium cruentum by sodium
      dodecyl sulfate/polyacrylamide gel electrophoresis. A blue polypeptide from
      phycobilisomes had absorption and fluorescence emission spectra similar to those
      of allophycocyanin. A green-pigmented polypeptide from photosynthetic membranes
      (free of phycobilisomes) contained chlorophyll a. Several properties were common
      to the M(r) 95,000 polypeptides from both sources: (i) identical molecular
      weights, (ii) identical gel electrophoresis patterns after limited protease
      digestion, and (iii) immunological crossreactivity with an IgG fraction directed
      against the M(r) 95,000 polypeptide from phycobilisomes. On the basis of this
      evidence, a common polypeptide exists in phycobilisomes and thylakoids, and it
      probably anchors the phycobilisome to the thylakoid membrane. The fluorescence
      emission overlap of the blue and green polypeptides suggests that they are
      involved in the transfer of energy from phycobilisomes to thylakoids.

PMID- 16593228
TI  - Two-fluid theory and thermodynamic properties of liquid mixtures: Application to
      simple mixtures of nonelectrolytes.
AB  - In this last of three articles describing a two-fluid theory of liquid mixtures,
      the important result is a derivation of local compositions to describe
      nonrandomness (clustering) of mixing. The model is applied to the system
      methane/tetrafluoromethane. Although it appears that the two-fluid theory with
      local compositions may provide an improvement over random-mixing theories, it is
      likely that the use of local compositions overestimates the effect of
      nonrandomness.

PMID- 16593229
TI  - Photodissociation of water by p- and n-type polycrystalline iron oxides by using
      visible light (</=2.7 eV) in the absence of external potential.
AB  - A polycrystalline p/n diode assembly, consisting of pressed magnesium- and
      silicon-doped iron oxide powders, has been shown to photodissociate water by
      using visible light in the absence of any external potential. In the investigated
      pH range (8-14) the device produces hydrogen catalytically in amounts that are
      readily detectable by gas chromatography. The relatively low-power conversion
      efficiency of 0.05% is believed to be due to the poor change-transfer properties
      of the p-type iron oxide used.

PMID- 16593230
TI  - Multilinear Littlewood-Paley estimates with applications to partial differential
      equations.
AB  - We obtain a collection of multilinear Littlewood-Paley estimates, which we then
      apply to two problems in partial differential equations. The first problem is the
      estimation of the square root of an elliptic operator in divergence form, and the
      second is the estimation of solutions to the Cauchy problem for nondivergence
      form parabolic equations.

PMID- 16593231
TI  - Geometry and analysis of Shimizu L-functions.
AB  - The values of 0 of Shimizu L-functions are realized as the signature defects of
      framed manifolds. This settles a conjecture of Hirzebruch [Hirzebruch, F. (1973)
      Enseign. Math. 19, 183-281] affirmatively. The proof employs the spectral theory
      of elliptic operators.

PMID- 16593232
TI  - Isolation and function of spinach leaf beta-ketoacyl-[acyl-carrier-protein]
      synthases.
AB  - Crude spinach leaf extract readily forms the stearoyl derivative of acyl-carrier
      protein (ACP) when acetyl-ACP and malonyl-ACP are incubated together. Palmitoyl
      ACP is also elongated by malonyl-ACP to stearoyl-ACP. When beta-ketoacyl-ACP
      synthase {3-oxoacyl-[ACP] synthase; acyl-[ACP]:malonyl-[ACP] C-acyltransferase
      (decarboxylating), EC 2.3.1.41} is purified with decanoyl-ACP as the assay
      substrate, palmitoyl-ACP elongation activity is lost. When palmitoyl-ACP is the
      assay substrate, another protein is isolated that specifically elongates
      palmitoyl-ACP to beta-ketostearoyl-ACP but has no activity towards decanoyl-ACP.
      The first protein is designated beta-ketoacyl-ACP synthase I and participates in
      the conversion of acetyl-ACP to palmitoyl-ACP, whereas the second protein is
      designated beta-ketoacyl-ACP synthase II, and its substrate specificity is highly
      restricted to myristoyl-ACP and palmitoyl-ACP. The purification of synthase II is
      described, and its activity is compared to synthase I. Reconstitution experiments
      with the highly purified nonassociated enzymes in fatty acid synthesis plus
      synthases I and II clearly demonstrate the roles of these two proteins in fatty
      acid synthesis.

PMID- 16593233
TI  - O isotope shift in N NMR analysis of biological N-oxidations: H(2)O-NO(2)
      exchange in the ammonia-oxidizing bacterium Nitrosomonas.
AB  - The (18)O/(16)O shifts in (15)N NMR were determined for nitrite (0.13 ppm or 4.2
      Hz at 7.05 T) and nitrate (0.056 ppm or 1.7 Hz at 7.05 T) at neutral pH. The
      technique, which allows clear differentiation between (16)O and (18)O derivatives
      of (15)N, was used to assess the source of oxygens in nitrite produced by
      oxidation of ammonia in Nitrosomonas. The two oxygens of nitrite produced by cell
      catalyzed oxidation of ammonia or hydroxylamine had the (16)O/(18)O isotope
      composition of water. Nitrosomonas is shown to catalyze the rapid exchange of
      oxygen between nitrite and water. The exchange reaction required the concomitant
      oxidation of ammonia. The amount of nitrite exchanged could exceed the amount of
      ammonia oxidized by a factor of 3. This exchange explains previous difficulties
      in the determination of the source of nitrite oxygen in ammonia oxidation. When
      cells oxidized [(15)N]ammonia in the presence of a great excess of exogenous
      [(14)N]nitrite, 20% of one oxygen in the resulting [(15)N]nitrite was derived
      from dioxygen. Dioxygen is apparently the source of at least one oxygen in
      nitrite produced by Nitrosomonas.

PMID- 16593234
TI  - Mapping the mitochondrial DNA of Zea mays: Ribosomal gene localization.
AB  - We have located the 18S and 26S ribosomal genes on a 32.2-kilobase pair (kb)
      restriction map of Zea mays mitochondrial DNA. In a BamHI restriction digest of
      mitochondrial DNA, band 4 carries all of the 26S gene whereas band 2 carries the
      18S gene sequence. We have cloned and mapped bands 2 and 4 and show that they are
      contiguous in the genome. The 26S sequence is at one end of the 13.7-kb fragment
      4, immediately adjacent to the junction with fragment 2. The 18S sequence is
      located at the far end of the 17.5-kb fragment 2, about 15 kb away from the 26S
      gene. A second region of 18S sequence homology is found on band 40. This region
      contains sequences that cross-hybridize with those in band 2. The nature of this
      apparent sequence repetition is unclear.

PMID- 16593235
TI  - Ricin inhibition of in vitro protein synthesis by plant ribosomes.
AB  - In vitro translation systems were prepared with supernatant factors from wheat
      germ and 80S ribosomes from wheat germ, barley embryos, watermelon cotyledons,
      pea cotyledons, and castor bean endosperm. Ricin A-chain, which strongly inhibits
      protein synthesis by mammalian ribosomes, inhibited all of the plant ribosomal
      systems by 50% when present at 25-45 mug/ml- approximately 23,000 times the
      concentration needed to inhibit mammalian systems. Ricinus communis agglutinin A
      chain, a protein similar to ricin A-chain, inhibited translation by the plant
      systems 50% at concentrations 5-10 times those of the ricin A-chain. Ribosomes
      from castor bean endosperm, the source of ricin and the agglutinin, were just as
      susceptible to the inhibitors as were ribosomes from the other four plants.
      Compartmentation of the inhibitors within vacuoles derived from protein bodies of
      the endosperm appears to be responsible for protecting cytoplasmic protein
      synthesis during germination of castor beans.

PMID- 16593236
TI  - Immunological similarity between a cyanobacterial enzyme and a nuclear DNA
      encoded plastid-specific isozyme from spinach.
AB  - The immunochemical properties of the plastid and cytosolic isozymes of
      phosphoglucose isomerase (glucosephosphate isomerase; D-glucose-6-phosphate ketol
      isomerase, EC 5.3.1.9) in spinach (Spinacia oleracea) and the single
      phosphoglucose isomerase enzyme from the cyanobacterium Synechococcus sp. were
      compared by an application of the enzyme-linked immunosorbent assay. Utilizing
      antibodies made in rabbits against subunits of purified plastid and cytosolic
      phosphoglucose isomerase isozymes from spinach, we demonstrate that the plastid
      isozyme is immunochemically more similar to the cyanobacterial enzyme than to the
      spinach cytosolic counterpart. The antiserum to plastid phosphoglucose isomerase
      crossreacted strongly with plastid phosphoglucose isomerases from other flowering
      plants. The antiserum to cytosolic phosphoglucose isomerase crossreacted with
      other plant cytosolic phosphoglucose isomerase isozymes. The results are
      consistent with the hypothesis [Weeden, N. F. (1981) J. Mol. Evol. 17, 133-139]
      that the nuclear gene specifying plastid phosphoglucose isomerase was derived
      from a prokaryote after the incorporation of a plastid-like symbiont into the
      ancestral plant cell.

PMID- 16593237
TI  - Tissue-specific regulation of gene function: Presetting and erasure.
AB  - Evidence is presented for presetting and erasure at the P locus of maize. The
      presence of an Mp transposable controlling element in the P(vv) allele affects
      the presetting and thus the regulation of gene function in different tissues.

PMID- 16593238
TI  - Structures of the genes for the beta and epsilon subunits of spinach chloroplast
      ATPase indicate a dicistronic mRNA and an overlapping translation stop/start
      signal.
AB  - A 2,4-kilobase-pair region of spinach chloroplast DNA adjacent to the gene for
      the large subunit of ribulosebisphosphate carboxylase has been analyzed by RNA
      hybridization, in vitro transcription/translation, and DNA sequence
      determination. The analysis indicates that this region carries the genes for the
      beta and epsilon subunits of chloroplast ATPase and that the two genes are
      cotranscribed into a dicistronic mRNA with 4-base-pair overlap between the stop
      codon of the beta-subunit gene and the start codon of the epsilon-subunit gene.
      The ATPase and carboxylase genes are transcribed divergently with respect to each
      other. The deduced amino acid sequences of the beta and epsilon subunits from
      spinach show 67% and 26% homology, respectively, with the published sequences of
      the beta and epsilon subunits of Escherichia coli ATPase.

PMID- 16593239
TI  - Properties of a cell-free system for synthesis of citrus exocortis viroid.
AB  - Partially purified nuclei from citrus exocortis viroid (CEV)-infected Gynura
      aurantiaca are able to synthesize linear and circular viroid molecules.
      Pretreatment of the nuclei with actinomycin D or deoxyribonuclease did not affect
      viroid synthesis, whereas the synthesis of other cellular RNAs was severely
      reduced. These observations support the essential role of CEV complementary RNA
      sequences in viroid replication. However, when alpha-amanitin was included in
      this in vitro synthesis system, CEV replication was markedly reduced by
      concentrations of 10 nM or greater. Taken together, these data support the
      proposition that viroid synthesis is catalyzed by a DNA-dependent RNA polymerase
      acting on a RNA template.

PMID- 16593240
TI  - Translation of mRNAs for subunits of chloroplast coupling factor 1 in spinach.
AB  - The chloroplast coupling factor 1 consists of five nonidentical subunits, three
      of which (alpha, beta, and epsilon subunits) have been shown in several
      laboratories to be synthesized within chloroplasts. The site of synthesis of the
      remaining two (gamma and delta subunits) was investigated by analyzing products
      directed by spinach leaf RNAs in wheat germ and reticulocyte translation systems
      in vitro. It was found that poly(A)(+) RNA directs the synthesis of two distinct
      polypeptides, one of which is immunochemically related to the gamma subunit but
      is 4,000 daltons larger. The other shares antigenic sites with the delta subunit
      but is 8,000 daltons larger. When wheat germ or reticulocyte translation systems
      were programmed with RNAs from purified chloroplasts, the only products related
      to CF(1) that we could detect were a putative precursor of beta, 2,000 daltons
      larger than the mature subunit, and some smaller polypeptides, which appear to be
      incomplete translation products of beta. From these results it appears likely
      that the gamma and delta subunits are synthesized in the cytoplasm as larger
      precursors and that beta is synthesized within the chloroplast as a precursor.

PMID- 16593242
TI  - Appropriate constraints for variational optimization of electronic density
      matrices and electron densities.
AB  - Euler equations characteristic of the electronic reduced density matrix have
      previously been obtained by minimizing an energy functional subject to trace
      constraints P(K) = N, in which N is the number of particles. It is shown that
      these constraints are inadequate to exclude variations that violate N
      representability conditions. However, a first-order reduced density matrix that
      does satisfy N-representability conditions is formulated as a functional of the
      orbital densities through use of angular momentum recoupling. Modified
      variational constraints are proposed.

PMID- 16593243
TI  - Excluded-volume effect on quasi-elastic light scattering by flexible
      macromolecules.
AB  - First-order perturbation expressions are developed for the first cumulant
      (initial time derivative) of the dynamic structure factor observable by photon
      correlation measurements of the light scattered by flexible chain molecules in
      solution. A dimensionless coefficient C, which measures the initial departure of
      the first cumulant from proportionality to the square of the scattering vector,
      is found to be only slightly altered by excluded-volume effects.

PMID- 16593241
TI  - Short direct repeats flank the T-DNA on a nopaline Ti plasmid.
AB  - Crown gall disease results from the insertion of a segment of the Agrobacterium
      Ti plasmid, called T-DNA, into host plant nuclear DNA. We have subjected to
      sequence analysis the border regions of pTi T37 (ends of T-DNA) and one left T
      DNA/plant DNA border fragment isolated from BT37 tobacco teratoma by molecular
      cloning. These sequence studies, taken together with published sequence of a
      right T-DNA/plant DNA border fragment, allowed us to identify the positions of
      left and right borders at the DNA sequence level. Comparison of left and right
      border regions of the Ti plasmid revealed a "core" direct repeat of 13 of 14
      bases (12 contiguous) precisely at the borders of T-DNA. An extended repeat of 21
      of 25 bases overlaps this core repeat. T-DNA on the Ti plasmid exhibits no longer
      direct or inverted repeats in the border regions, based on Southern hybridization
      studies. The physical structure of T-DNA differs from that of known prokaryotic
      and eukaryotic transposable elements but bears a structural resemblance to the
      prophage of bacteriophage lambda.

PMID- 16593244
TI  - Gravitational field of a charged mass point.
AB  - Adopting, with Schwarzschild, the Einstein gauge ((munu) = -1), a solution of
      Einstein's field equations for a charged mass point of mass M and charge Q is
      derived, which differs from the Reissner-Nordstrom solution only in that the
      variable r is replaced by R = (r(3) + a(3))((1/3)), where a is a constant. The
      Newtonian gravitational potential psi identical with (2/c(2))(1 - g(00)) obeys
      exactly the Poisson equation (in the R variable), with the mass density equal to
      (E(2)/4pic(2)), E denoting the electric field. psi also obeys a second linear
      equation in which the operator on psi is the square root of the Laplacian
      operator. The electrostatic potential Phi (= Q/R), psi, and all the components of
      the curvature tensor remain finite at the origin of coordinates. The
      electromagnetic energy of the point charge is finite and equal to (Q(2)/a). The
      charge Q defines a pivotal mass M(*) = (Q/G((1/2))). If M < M(*), then the whole
      mass is electromagnetic. If M > M(*), the electromagnetic part of the mass M(em)
      equals [M - (M(2) - M(*2))((1/2))], whereas the material part of the mass M(mat)
      equals (M(2) - M(*2))((1/2)). When M > M(*), the constant a is determined,
      following Schwarzschild, by shrinking the "Schwarzschild radius" to zero. When M
      < M(*), a is determined so as to make the gravitational acceleration vanish at
      the origin.

PMID- 16593245
TI  - Amino acid sequence of a basic blue protein from cucumber seedlings.
AB  - The amino acid sequence of a type 1 copper protein, the 96-residue basic blue
      protein from cucumber seedlings, has been determined by Edman degradation of the
      intact molecule and of fragments produced by cleavage with cyanogen bromide and
      with trypsin. The cucumber basic blue protein shows a marked sequence homology
      with stellacyanin, and to a smaller degree with plastocyanin and azurin. The
      known copper ligands of plastocyanin and azurin (corresponding to histidine-37,
      cysteine-84, histidine-87, and methionine-92 in plastocyanin) are present in the
      cucumber basic blue protein. However, the latter also contains a half-cystine
      residue analogous to the suggested fourth ligand of stellacyanin, where
      methionine is absent.

PMID- 16593246
TI  - Primary photochemistry in the facultatively aerobic green photosynthetic
      bacterium Chloroflexus aurantiacus.
AB  - Photochemical activity was examined in membrane fragments and a purified membrane
      preparation from Chloroflexus. Flash-induced absorption difference spectroscopy
      strongly suggests a primary donor (P(865)) that is more similar to the P(870)
      bacteriochlorophyll a dimer found in the purple photosynthetic bacteria than it
      is to P(840) found in the anaerobic green bacteria. Redox measurements on P(865)
      and an early acceptor also indicate a photochemical system characteristic of the
      purple bacteria. The membrane preparation contains a tightly bound type c
      cytochrome, c(554), that is closely coupled to the reaction center as indicated
      by its ability to rereduce photooxidized P(865). Chloroflexus thus appears to be
      distinct photochemically from other families of photosynthetic bacteria and may
      occupy an important role in photosynthetic evolution.

PMID- 16593247
TI  - Sequence of the gene coding for the beta-subunit of dinitrogenase from the blue
      green alga Anabaena.
AB  - The nitrogen fixation nif K gene of the blue-green alga Anabaena, which codes for
      the beta-subunit of dinitrogenase, has been subjected to sequence analysis. The
      nif K protein is predicted to be 512 amino acids long, to have a M(r) or 57,583,
      and to contain six cysteine residues. Three of these cysteines are within
      peptides homologous to FeS cluster-binding cysteinyl peptides from ferredoxins
      and from a high potential iron protein and, thus, may be ligands to which FeS
      clusters bind in dinitrogenase. The sequences surrounding the cysteine residues
      are 70% homologous to the corresponding cysteinyl tryptic peptides of the
      Azotobacter vinelandii dinitrogenase, although the positions of the cysteine
      residues are not always conserved between the two proteins. A 15-amino acid
      coding sequence precedes nif K on its transcript. Amino acid codon usage is
      highly asymmetric and parallels that found for the Anabaena dinitrogenase
      reductase gene (nif H). Putative promoter and ribosome binding site sequences
      were identified for nif K. These regulatory sequences are homologous to sequences
      preceding nif D; nif D codes for the alpha-subunit of dinitrogenase but is
      separated from nif K on the chromosome by 11,000 nucleotides. The nif K promoter
      also is virtually identical to a promoter-like sequence that immediately precedes
      the start of the transcript for the large subunit of ribulosebisphosphate
      carboxylase from maize chloroplasts. This homology appears to support the theory
      that chloroplasts evolved from blue-green algae.

PMID- 16593248
TI  - Isolation of a Caulobacter gene cluster specifying flagellum production by using
      nonmotile Tn5 insertion mutants.
AB  - Caulobacter crescentus assembles a single polar flagellum from protein components
      synthesized at a specific time in the cell cycle. Of the 26 genes required for
      flagellum production, at least 4 of them-flaY, E, F, and G-map together in a
      single cluster. We have isolated DNA from this region of the chromosome by using
      a nonmotile mutant with a Tn5 insertion into flaE. C. crescentus DNA carrying the
      Tn5-flaE region and adjacent sequences was cloned into pBR325 and selected by
      transposon-encoded kanamycin resistance. The resulting plasmid was used as a
      probe to isolate the flaE region from a wild-type gene bank and to determine the
      chromosomal location of several deletion and insertion mutations within the
      flaY/E/F/G cluster. At least three promotors and three major transcripts were
      shown to originate from the cloned gene cluster. The role of these genes in
      flagellar biogenesis was examined by immunoprecipitation of mutant cell extracts
      with antiflagellin antibody. Deletions extending rightward into this gene cluster
      eliminated one of the two flagellin proteins normally synthesized by C.
      crescentus. Mutations mapping to the left permitted synthesis of both normal
      flagellins but at significantly decreased levels. These results suggest that the
      leftward end of this cluster contains a region that may function in a regulatory
      capacity whereas the rightward end may contain sequences overlapping a flagellin
      structural gene.

PMID- 16593249
TI  - Purification, primary structure, and homology relationships of a chloroplast
      ribosomal protein.
AB  - A chloroplast ribosomal protein that showed immunological homology to Escherichia
      coli ribosomal protein L12 was purified from spinach (Spinacia oleracea) leaves
      and its primary structure was determined by manual micro Edman degradation. The
      protein is composed of 130 amino acid residues and has M(r) 13,576. It shows
      structural features characteristic of the L12 proteins of eubacterial 70S
      ribosomes (e.g., identical amino acid residues in about 50% of the sequence) but
      no apparent homology to the L12-type proteins of eukaryotic cytoplasmic 80S
      ribosomes. The homology to eubacterial proteins is highest in the COOH-terminal
      region (70%) and low in the NH(2)-terminal region (<20%).

PMID- 16593250
TI  - Location and nucleotide sequence of the gene for the proton-translocating subunit
      of wheat chloroplast ATP synthase.
AB  - The proton-translocating subunit of wheat chloroplast ATP synthase is encoded by
      a chloroplast gene that has been accurately mapped and whose nucleotide sequence
      has been determined. The predicted sequence of 81 amino acids has been confirmed
      in part by determination of the sequence of the first 40 amino acids from the
      NH(2) terminus of the protein, and it shows 100% homology with the known amino
      acid sequence of the spinach protein but no more than 35% homology with the amino
      acid sequences of bacterial and mitochondrial proteins. The gene shows no
      deviation from the "universal" genetic code and is not split. A potential
      ribosome binding site is located 12 nucleotides upstream from the initiation
      codon, but sequences homologous to prokaryotic promotors and transcription
      terminators are not apparent.

PMID- 16593251
TI  - Partial characterization of a phosphorylated intermediate associated with the
      plasma membrane ATPase of corn roots.
AB  - The phosphorylated protein associated with a deoxycholate-extracted plasma
      membrane fraction from corn (Zea mays L. var WF9 x Mol7) roots was characterized
      in order to correlate its properties with those of plasma membrane ATPase. Its
      phosphorylation, like that of plasma membrane ATPase, was dependent on Mg(2+),
      substrate specific for ATP, insensitive to azide, oligomycin, or molybdate, and
      sensitive to N,N'-dicyclohexylcarbodiimide, diethylstilbestrol, or vanadate.
      Monovalent cations affected the phosphorylation of the protein in a manner
      consistent with their stimulatory effects on ATPase. For K(+), this was shown to
      occur through an increase in the turnover of the phosphoenzyme. Analysis of the
      phosphorylated protein by NaDodSO(4)/polyacrylamide gel electrophoresis revealed
      the presence of a single labeled polypeptide with a molecular weight of about
      100,000. Phosphorylation of this polypeptide was dependent on Mg(2+), sensitive
      to K(+), and inhibited by vanadate. It is concluded that this polypeptide
      represents the catalytic subunit of the plasma membrane ATPase. These results are
      discussed in terms of a model for the coupling of metabolic energy to H(+) and
      K(+) transport in higher plants.

PMID- 16593252
TI  - Induction of pole cells in sterilized Drosophila embryos by injection of
      subcellular fraction from eggs.
AB  - A subcellular fraction isolated from a homogenate of young Drosophila embryos was
      shown to be capable of inducing pole cells when injected into UV-sterilized
      Drosophila embryos. Most of the pole cell-inducing activity was recovered from
      the precipitate after centrifugation at 27,000 x g. The activity remained in this
      precipitate (called F-3 fraction hereafter) even after membranous structures were
      removed from it through centrifugation on a sucrose density gradient. Dialysis,
      lyophilization, and heating at 80 degrees C for 10 min did not inactivate the F-3
      fraction. The pole cells, which were produced when the F-3 fraction was injected
      at the posterior pole of UV-sterilized embryos, did not develop into germ cells.
      Furthermore, the F-3 fraction was unable to induce pole cells when injected into
      the anterior region of the egg. These results can be explained by assuming that
      (i) pole cell formation and germ cell determination are controlled by different
      factors, (ii) pole cell formation requires at least two factors, which are
      normally localized in the posterior-pole cytoplasm, one of which is sensitive and
      one resistant to the UV dosage we used, and (iii) the subcellular fraction we
      obtained contains the UV-sensitive factor but not the UV-resistant factor.

PMID- 16593253
TI  - Evidence for a common ancestor sequence for the Balbiani ring 1 and Balbiani ring
      2 genes in Chironomus tentans.
AB  - The Balbiani ring (BR) 1 and BR 2 genes in Chironomus tentans are functionally
      related and are only expressed in the salivary gland cells. Here we reveal the
      principal structure of the BR 1 gene and analyze the structural and evolutionary
      relationship between the BR 1 and BR 2 genes. The properties of the BR 1 gene, 37
      kilobases in size, are derived from the analysis of a cloned cDNA sequence, pCt
      21. A considerable part of the BR 1 gene consists of one or a few blocks of a
      tandemly repeated 246-base-pair (bp) major repeat unit. About half of this major
      repeat unit is in turn built from four tandem repeats of a 33-bp sequence. This
      hierarchic arrangement of repetitive sequences within the BR 1 gene suggests that
      the gene has evolved through two major amplification steps, starting from a short
      primordial sequence. A similar evolutionary model has been put forward for the BR
      2 gene [Sumegi, J., Wieslander, L. & Daneholt, B. (1982) Cell 30, 579-587]. The
      two putative primordial genes contain a similar, 102-bp-long sequence (86%
      nucleotide sequence homology), indicating that the BR 1 and BR 2 genes most
      likely arose from the same ancestor sequence. During the course of evolution the
      two genes diverged, mainly due to differences in the length and sequence of the
      gene segments involved in the two amplification steps. Moreover, at least one of
      the BR genes was translocated to another chromosomal locus.

PMID- 16593254
TI  - Some spectrally isolated convex planar regions.
AB  - The basic question raised by M. Kac as to whether a domain in Euclidean space is
      determined by its Dirichlet spectrum remains open. In this note, dealing only
      with convex planar regions, we introduce a new countable family of (generic)
      spectral invariants of wave type, discuss some asymptotic properties of the
      distribution of closed geodesics, describe a partial converse to the Poisson
      relation, and thereby construct a two-parameter family of spectrally isolated
      regions, including the circles.

PMID- 16593255
TI  - Exterior gauging of an internal supersymmetry and SU(2/1) quantum
      asthenodynamics.
AB  - A formally unitary Lagrangian model gauging an internal supersymmetry is
      proposed. The even subalgebra is gauged as a Yang-Mills theory, while the odd
      generators are gauged-according to Freedman's method-by skew tensor fields,
      equivalent dynamically to scalar Higgs fields. Chiral fermions are incorporated
      by following Townsend's construction and form irreducible supermultiplets graded
      by their helicity. The application to quantum asthenodynamics is discussed.

PMID- 16593256
TI  - Rules governing the composition of revolving clusters in quasiband and prolate
      deformation states of atomic nuclei.
AB  - A set of rules, involving the magic and semimagic values of neutron and proton
      numbers and the proton/neutron ratio, is formulated for the composition of the
      revolving clusters producing the values of the moment of inertia given by the
      differences in energy of the adjacent levels in quasibands and bands of nuclei.
      The cluster compositions assigned with use of these rules to isotopes of Kr, Sr,
      Zr, Mo, and the actinon nuclei and to successive levels of the ground-state band
      of (158)Er lead to reasonable values of the radius of revolution (the distance
      from the center of the nonrevolving sphere to the center of the cluster). These
      values correspond to a spheron diameter of about 3.20 fm.

PMID- 16593257
TI  - Isolation of cloned cDNAs to auxin-responsive poly(A)RNAs of elongating soybean
      hypocotyl.
AB  - Auxin-responsive cDNA clones have been isolated from a cDNA library prepared from
      elongating soybean hypocotyl poly(A)(+)RNA. The expression of two such sequences
      has been assessed by RNA blot hybridization analyses during normal developmental
      transitions in the soybean hypocotyl and during incubation of sections excised
      from the region of cell elongation. The concentrations of these poly(A)(+)RNAs
      are higher in the elongating zone than in the apical and mature zones of the
      hypocotyl. Both poly(A)(+)RNAs are depleted during incubation of the sections in
      the absence of auxin. The loss of one of these sequences (pJCW1) is prevented by
      the addition of auxin to the incubation medium while the other sequence (pJCW2)
      increases above the initial level in the presence of auxin. The addition of auxin
      to auxin-depleted tissue in which the sequences are depleted results in rapid
      accumulation of these poly(A)(+)RNAs; pJCW1 accumulates to the control level
      while pJCW2 increases well above the control level. These data along with others
      [Baulcombe, D. C. & Key, J. L. (1980) J. Biol. Chem. 255, 8907-8913] demonstrate
      directly a highly selective effect of auxin on the expression of a small number
      of mRNAs in tissues undergoing both cell elongation and cell division in response
      to auxin. Although the data are suggestive of a close association betwen auxin
      action and altered gene expression, a causal relationship is not established. It
      seems highly unlikely, however, that such specific effects of auxin on gene
      expression are unimportant in auxin physiology.

PMID- 16593258
TI  - Radical pair state in photosystem II.
AB  - A stable light-induced EPR signal is reported in photosystem II particles and in
      chloroplasts at 5 K. Characteristic spectral features indicate that the signal
      arises from dipole-dipole interactions of a radical pair triplet state. From its
      dependence on potential, its relationship to the spin-polarized triplet state,
      and the redox state of the pheophytin acceptor (Ph) and because it is present in
      Tris-washed chloroplasts but not in untreated chloroplasts, we conclude that the
      signal is formed when the reaction center is in the state D(+)P(680)Ph(-) (P(680)
      is the primary chlorophyll donor and D(+) is an oxidized donor to P(680)). The
      low-temperature photochemical sequence is thought to occur as follows. (i)
      Donation from D to the P(680) (+)Ph(-) state occurs at liquid helium temperature
      in low quantum yield; this reaction is reversible at temperatures above 5 K. (ii)
      In normal chloroplasts, donation occurs to the D(+)P(680)Ph(-) state, but this
      does not occur in Tris-washed chloroplasts or in the photosystem II particles at
      77 K or lower. (iii) Illumination, at 200 K, of photosystem particles or Tris
      washed chloroplasts results in donation to the D(+)P(680)Ph(-) state from another
      donor. From experiments in the absence of redox mediators and the temperatures
      dependence of the splitting of the signal, it is suggested that the state
      D(+)P(680)Ph(-) itself may be the origin of the radical pair triplet signal. The
      signal has been simulated by assuming the presence of at least two distinct
      radical pairs that differ slightly in the distance separating the radicals of the
      pairs. The distance between the radicals of the pair is calculated to be 6-7 A.

PMID- 16593259
TI  - Cytoplasmic male sterility in barley: Evidence for the involvement of cytokinins
      in fertility restoration.
AB  - The hypothesis of the association between an increase in cytokinin activity and
      restoration of anther fertility in msm1 cytoplasm was tested. The following
      barley lines with Hordeum vulgare cv. Adorra nuclear gene background were
      studied: Adorra cytoplasm without nuclear restorer gene (fertile), Adorra
      cytoplasm homozygous for nuclear Rfm1a gene (fertile), msm1 cytoplasm without
      restorer gene (male sterile), msm1 cytoplasm homozygous for nuclear Rfm1a gene
      (fertile). Ethanolic extracts of root exudate were fractionated and bioassayed
      for cytokinins. Both the biological activity and the total quantity of cytokinins
      appeared lowest in the unrestored male sterile line. The total biological
      activities of cytokinins in the three fertile lines were similar, but the
      quantities in the restorer gene carriers appeared lower. On the other hand, the
      restorer gene carriers, independent of the cytoplasm, showed 8-9 times more of a
      bound cytokinin. Because the bound form is evidently underestimated by the
      bioassay, the increase in the bound cytokinin fraction may mean even a higher
      total content in the Rfm1a gene carriers than in Adorra without the gene. The
      bound cytokinin may be translocated more readily to distal organs (e.g., the
      anthers) compared with unbound cytokinins. Because cytokinins are associated with
      various ecophysiological processes, the rise in a particular form may explain the
      heterogeneous distribution of the restorer gene in wild barley populations in
      different regions of Israel.

PMID- 16593260
TI  - Structural diversity and differential light control of mRNAs coding for
      angiosperm glyceraldehyde-3-phosphate dehydrogenases.
AB  - Subunits A and B of chloroplast glyceraldehyde-3-phosphate dehydrogenase are
      synthesized as higher molecular weight precursors when polyadenylylated mRNA from
      angiosperm seedlings is translated in vitro by wheat germ ribosomes. The in vivo
      levels of mRNA coding for these precursors are strongly light dependent, and the
      increase in translational activity stimulated by continuous white light, relative
      to dark-grown seedlings, is at least 5- to 10-fold for the seven plant species
      investigated. As opposed to this, light does not seem to change mRNA levels
      coding for cytosolic glyceraldehyde-3-phosphate dehydrogenase, and the
      polypeptides synthesized in vitro have the same size as the authentic subunits.
      In addition, precursors of the chloroplast enzyme were identified for 12
      different angiosperm species and compared with their respective subunits
      synthesized in vivo. The patterns of the in vitro and in vivo products correlate
      in several major characteristics. They both display a remarkable interspecific
      heterogeneity with respect to size and number of polypeptides. The peptide
      extensions of the enzyme precursors calculated from these data vary between 4,000
      and 12,000 daltons and seem to fall into three major size classes. The present
      data demonstrate that chloroplast glyceraldehyde-3-phosphate dehydrogenase, like
      its cytosolic counterpart, is encoded in the nucleus. Yet, the two dehydrogenases
      are controlled differently at both the ontogenetic and phylogenetic levels. They
      follow separate biosynthetic pathways with respect to light regulation, post
      translational processing, and transport and also exhibit different evolutionary
      rates. The fast evolutionary change observed for the chloroplast enzyme contrasts
      sharply with the conservative structure and sequence of the cytosolic enzyme.

PMID- 16593261
TI  - Bent helical structure in kinetoplast DNA.
AB  - We have investigated the unusual physical properties of a restriction fragment of
      Leishmania tarentolae kinetoplast DNA. A gel-purified fragment comprising
      slightly more than half of a minicircle was determined by Maxam-Gilbert sequence
      determination to be 490 base pairs (bp) in length. This fragment has dramatically
      anomalous electrophoretic behavior; it has an apparent size of 450 bp on a 1%
      agarose gel but migrates as 1,380 bp on a 12% polyacrylamide gel. However, in gel
      filtration on Sephacryl S-500, the fragment elutes with an apparent size of 375
      bp. Finally, it behaves anomalously in electric dichroism experiments. Field-free
      rotational relaxation times from transient electric dichroism studies are highly
      sensitive to effective molecular dimensions. The rotational relaxation time of
      the kinetoplast fragment is smaller than that of a 309-bp control fragment from
      pBR322. Because rigorous control experiments rule out the possibility that this
      fragment is modified, these anomalous properties must be dictated by the sequence
      itself. Fragment behavior indicates that it has an unusually compact
      configuration; we propose that this molecule contains a region of systematically
      bent B-DNA. This model accounts for the fragment's difficulty in snaking through
      the pores of a polyacrylamide gel, its ease in diffusing into Sephacryl beads,
      and its smaller rotational relaxation time. Bending of this molecule may be
      caused by periodicities in the DNA sequence.

PMID- 16593262
TI  - Nucleotide sequence of the gene for the M(r) 32,000 thylakoid membrane protein
      from Spinacia oleracea and Nicotiana debneyi predicts a totally conserved primary
      translation product of M(r) 38,950.
AB  - The gene for the so-called M(r) 32,000 rapidly labeled photosystem II thylakoid
      membrane protein (here designated psbA) of spinach (Spinacia oleracea)
      chloroplasts is located on the chloroplast DNA in the large single-copy region
      immediately adjacent to one of the inverted repeat sequences. In this paper we
      show that the size of the mRNA for this protein is approximately 1.25 kilobases
      and that the direction of transcription is towards the inverted repeat unit. The
      nucleotide sequence of the gene and its flanking regions is presented. The only
      large open reading frame in the sequence codes for a protein of M(r) 38,950. The
      nucleotide sequence of psbA from Nicotiana debneyi also has been determined, and
      comparison of the sequences from the two species shows them to be highly
      conserved (>95% homology) throughout the entire reading frame. Conservation of
      the amino acid sequence is absolute, there being no changes in a total of 353
      residues. This leads us to conclude that the primary translation product of psbA
      must be a protein of M(r) 38,950. The protein is characterized by the complete
      absence of lysine residues and is relatively rich in hydrophobic amino acids,
      which tend to be clustered. Transcription of spinach psbA starts about 86 base
      pairs before the first ATG codon. Immediately upstream from this point there is a
      sequence typical of that found in E. coli promoters. An almost identical sequence
      occurs in the equivalent region of N. debneyi DNA.

PMID- 16593263
TI  - Photoaffinity labeling with 2-azidoadenosine diphosphate of a tight nucleotide
      binding site on chloroplast coupling factor 1.
AB  - An analog of ADP containing an azido group at the C-2 position of the purine ring
      has been synthesized and used as an affinity probe of the membrane-bound coupling
      factor 1 of spinach chloroplast thylakoid membranes. The 2-azido-ADP inhibited
      light-induced dark binding of ADP at the tight nucleotide binding site on the
      thylakoid membranes. The 2-azido-ADP itself bound tightly to the thylakoid
      membranes, with 1 muM as the concentration giving 50% maximum binding. Tight
      binding of the analog required the thylakoid membranes to be energized, and the
      nucleotide remained bound after repeated washings of the membranes. The maximum
      extent of tight binding of the analog (1,2-1.3 nmol/mg of chlorophyll) was
      stoichiometric with the known coupling factor 1 content of thylakoid membranes
      but somewhat higher than that observed for ADP (0.5-0.9 nmol per mg of
      chlorophyll). Tight binding of 2-azido-ADP was decreased by the simultaneous
      addition of ADP. UV photolysis of washed thylakoid membranes containing tightly
      bound 2-azido-[beta-(32)P]ADP resulted in the covalent incorporation of label
      into the membranes. Isolation of the chloroplast coupling factor 1 from these
      membranes followed by NaDodSO(4) gel electrophoresis demonstrated that the analog
      was covalently bound to the beta subunit of the coupling factor complex.

PMID- 16593264
TI  - On a generalization of a theorem of Erich Hecke.
AB  - E. Hecke initiated the application of representation theory to the study of cusp
      forms. He showed that, for p a prime congruent to 3 mod 4, the difference of
      multiplicities of certain conjugate representations of SL(F(p)) on cusp forms of
      degree 1, level p, and weight >/=2 is given by the class number h(-p) of the
      field Q( radical-p). We apply the holomorphic Lefschetz theorem to actions on the
      Igusa compactification of the Siegel moduli space of degree 2 to compute the
      values of characters of the representations of Sp(4)(F(p)) on certain spaces of
      cusp forms of degree 2 and level p at parabolic elements of this group. Our
      results imply that here too, the difference in multiplicities of conjugate
      representations of Sp(4)(F(p)) is a multiple of h(-p).

PMID- 16593265
TI  - Inequalities for ratios of functionals of harmonic functions.
AB  - We show that the ratios (A(u)/N(u))(k)A(u) and (N(u)/A(u))(k)N(u) have L(p) norms
      equivalent with the H(p) norm of u. Here A(u) is the Lusin area integral and N(u)
      is the nontangential maximal function.

PMID- 16593266
TI  - Chronometric cosmology and fundamental fermions.
AB  - It is proposed that the fundamental fermions of nature are modeled by fields on
      the chronometric cosmos that are not precisely spinors but become such only in
      the nonchronometric limit. The imbedding of the scale-extended Poincare group in
      the linearizer of the Minkowskian conformal group defines such fields, by
      induction.

PMID- 16593267
TI  - A report on high-energy physics.

PMID- 16593268
TI  - Construction of a Rhizobium japonicum gene bank and use in isolation of a
      hydrogen uptake gene.
AB  - A gene bank of Rhizobium japonicum DNA was constructed by using the broad host
      range conjugative cosmid pLAFR1. Eighty-three percent of the clones in the bank
      contained cosmids with insert DNA averaging 22.6 kilobase pairs in length. A
      series of cosmids containing a hydrogen uptake (hup) gene was identified by
      transferring the gene bank into a H(2) uptake-negative (Hup(-)) R. japonicum
      point mutant (PJ17nal) and screening tetracycline-resistant colonies for the
      ability to grow chemolithotrophically and to reduce methylene blue in a recently
      devised colony assay. Hup(+) transconjugants arose at a frequency of
      approximately 6 x 10(-3). Plasmid DNAs from II of the Hup(+) transconjugants were
      isolated and used to transform Escherichia coli. EcoRI digests of all plasmids
      isolated from Hup(+) transconjugants had three DNA fragments in common. Eight of
      the E. coli transformants containing hup gene cosmids were conjugated with
      PJ17nal and another Hup(-) point mutant, PJ18nal. All PJ17nal transconjugants
      were Hup(+). The frequency of Hup(+) transconjugants with PJ18nal was
      approximately 10(-3). The results indicate that the hup gene cosmids may contain
      one gene and a portion of another.

PMID- 16593269
TI  - Isolation and spectral characterization of photochemical reaction centers from
      the thermophilic green bacterium Chloroflexus aurantiacus strain J-10-f1.
AB  - A rapid procedure has been devised to extract photochemically active reaction
      centers from the green bacterium Chloroflexus aurantiacus strain J-10-f1 and a
      mutant lacking colored carotenoids (73-3). The isolated material was completely
      free of antenna bacteriochlorophyll and cytochromes and nearly free of
      carotenoids and had near IR absorption maxima at 865, 815, and 756 nm. On
      oxidation, the peak at 865 nm was bleached and the remaining two peaks were
      shifted to 806 and 757 nm. Although these spectral characteristics show general
      similarities to those in reaction center preparations from purple bacteria, there
      are some distinct differences. Comparison of the spectra of reaction centers of
      Chloroflexus and Rhodopseudomonas sphaeroides, adjusted to the same absorbance at
      865 nm, showed that the absorbance at 815 nm in Chloroflexus was much less and
      that at 757 nm was much greater than the equivalent absorbances in R.
      sphaeroides. Unlike reaction centers from R. sphaeroides and other photosynthetic
      bacteria that have two molecules of bacteriopheophytin and four molecules of
      bacteriochlorophyll per unit, reaction centers from Chloroflexus appear to have
      three molecules of each pigment per unit. A prominent shoulder at 793 nm
      disappears concomitantly with the bleaching at 865 nm on oxidation of
      Chloroflexus reaction centers; this spectral component may represent the higher
      energy transition in the near IR of the two bacteriochlorophylls forming P865.
      While Chloroflexus has a light-harvesting pigment system very similar to that of
      the Chlorobiaceae, its reaction center has optical absorption characteristics
      similar to those of the Rhodospirillaceae.

PMID- 16593270
TI  - Cytokinin/auxin balance in crown gall tumors is regulated by specific loci in the
      T-DNA.
AB  - Insertion of the transposon Tn5 into the T-region of the octopine Ti plasmid of
      Agrobacterium tumefaciens gives rise to crown gall tumors having altered
      morphology. Three loci within the T-DNA that control tumor morphology have been
      detected [Garfinkel, D. J., Simpson, R. B., Ream, L. W., White, F. F., Gordon, M.
      P. & Nester, E. W. (1981) Cell 27, 143-153]. They influence tumor size (tml),
      production of roots (tmr), or production of shoots (tms). Cytokinin and auxin
      levels in such mutant tumors were examined by HPLC/radioimmunoassay and
      HPLC/fluorescence assay, respectively. Free indoleacetic acid levels (in pmol/g)
      were: uninfected tobacco stem tissues, 128; wild-type A348 tumors, 295; tml
      mutant tumors, 307; tmr mutant tumors, 129; and tms mutant tumors, 70. Average
      trans-ribosylzeatin levels were correspondingly: 0.97, 48, 40, 0.54, and 1,400
      pmol/g. trans-Ribosylzeatin/indoleacetic acid ratios were as high as 24 in shoot
      producing tumors and as low as 0.003 in root-producing tumors. The evidence
      strongly suggests that tumor phytohormone levels are determined by genes in the T
      DNA.

PMID- 16593271
TI  - RNA-dependent RNA polymerases of plants.
AB  - The existence of RNA-dependent RNA polymerases (EC 2.7.7.48) in plants has been
      definitely proven by their isolation in pure form from cucumber and tobacco in
      our laboratory and from cowpea at Wageningen. These enzymes are single-chain
      proteins of 100-130 kilodaltons. They show clear physical and biochemical
      differences characteristic for a given plant species, even when their amounts in
      the plants were greatly increased prior to isolation by infection with the same
      virus. The role of these enzymes in plant physiology remains unknown.

PMID- 16593272
TI  - Species-specific gating of gametangial dehiscence as a temporal reproductive
      isolating mechanism in Coelomomyces.
AB  - Hybridzygotes of Coelomomyces dodgei and Coelomomyces punctatus can be produced
      in the laboratory by making reciprocal crosses of their gametes. Although the
      F(1) hybrid sporophyte is viable, the F(1) gametophyte is inviable. Gametangial
      dehiscence (gamete release) in both species is relatively synchronous and follows
      a photoperiod-dependent diel periodicity, but even in populations grown under
      identical conditions, the gametes of each species are released during
      significantly different time frames. When the fungi are reared on an 8/16-hr
      dark/light regime, the gametes of C. punctatus are released during hours 7-11,
      whereas those of C. dodgei are released during hours 16-19. These results
      demonstrate that gametangial dehiscence is gated and, furthermore, indicate that
      this gating serves as a temporal reproductive isolating mechanism for these
      species of Coelomomyces. Additional preliminary studies with C. dodgei
      demonstrate that gametogenesis and gametangial dehiscence are photoperiod
      dependent functions triggered by the onset of the dark period during the last day
      of gametophyte development, a dark period as short as 2 hr being sufficient to
      stimulate gametogenesis and gametangial dehiscence.

PMID- 16593273
TI  - Influence of nuclear spin on chemical reactions: Magnetic isotope and magnetic
      field effects (A Review).
AB  - The course of chemical reactions involving radical pairs may depend on occurrence
      and orientation of nuclear spins in the pairs. The influence of nuclear spins is
      maximized when the radical pairs are confined to a space that serves as a cage
      that allows a certain degree of independent diffusional and rotational motion of
      the partners of the pair but that also encourages reencounters of the partners
      within a period which allows the nuclear spins to operate on the odd electron
      spins of the pair. Under the proper conditions, the nuclear spins can induce
      intersystem crossing between triplet and singlet states of radical pairs. It is
      shown that this dependence of intersystem crossing on nuclear spin leads to a
      magnetic isotope effect on the chemistry of radical pairs which provides a means
      of separating isotopes on the basis of nuclear spins rather than nuclear masses
      and also leads to a magnetic field effect on the chemistry of radical pairs which
      provides a means of influencing the course of polymerization by the application
      of weak magnetic fields.

PMID- 16593274
TI  - Experimental evidence that an asteroid impact led to the extinction of many
      species 65 million years ago.

PMID- 16593275
TI  - Linewidth of single laser-cooled Mg ion in radiofrequency trap.
AB  - A single Mg(+) has been successfully trapped and cooled in a small radiofrequency
      trap. The ion was cooled by using the radiation from a single-frequency ring dye
      laser whose output was doubled in frequency with an NH(4) (2)H(2)PO(4)
      temperature phasematched crystal; a power of about 22 muW or less was sufficient
      for all of the experiments. The ion temperature was estimated by a computer fit
      of the experimental resonance line profile; the resulting linewidth was compared
      to previously published Mg(+) 3(2)P(3/2) Hanle-effect linewidths. The result is a
      temperature of 5(-5) (+15) mK, which is lower than that attained previously.

PMID- 16593276
TI  - Association arrays in assessing forms of dependencies between bivariate random
      variables.
AB  - The bivariate distribution of pairs of random variables (X,Y) is said to be
      associated with respect to the classes of functions [unk] and [unk] if the
      product-moment correlation r[Phi(X),Psi(Y)] >/= 0 for all Phi euro [unk] and Psi
      euro [unk]. In the case in which both [unk] = [unk] = [unk](*) consist of all
      increasing functions, then the bivariate distribution of (X,Y) is said to be
      positive quadrant dependent. To apply the concept to data, I examine the
      correlations for classes of extremal functions that span by positive combinations
      the totality of functions Phi euro [unk] and Psi euro [unk] to investigate
      whether the pair of random variables (X,Y) are associated with respect to [unk]
      and [unk] and to assess the relative degree (or strength) of association when
      comparing two sets of random variables (X,Y) and (Z,W).

PMID- 16593277
TI  - Light-dependent assembly of ribulose-1,5-bisphosphate carboxylase.
AB  - Ribulose-1,5-bisphosphate carboxylase [RuP(2)Case; 3-phospho-D-glycerate carboxy
      lyase (dimerizing), EC 4.1.1.39] is composed of eight small subunits (M(r),
      14,000) and eight large subunits (M(r), 55,000). Newly synthesized large subunits
      are associated with two complexes having sedimentation coefficients of 7 and 29
      S. Assembly of RuP(2)Case occurs in isolated intact chloroplasts in the light but
      not in the dark. When extracts of chloroplasts are treated with ATP or GTP,
      RuP(2)Case assembly is accelerated while the 29S large subunit complex is
      maintained. In the presence of Mg(2+), ATP brings about almost complete
      dissociation of the 29S complex, whereas GTP and a nonhydrolyzable analog of ATP
      are without effect. These results indicate the existence of a complex set of
      reactions involving nucleotides, Mg(2+), and several putative intermediates in
      RuP(2)Case assembly. It is postulated that these reactions at least partly
      account for the light dependence of RuP(2)Case assembly. In particular, ATP and
      GTP promote the assembly of large subunits into RuP(2)Case.

PMID- 16593278
TI  - Relaxation processes for internal waves in mesoscale flow.
AB  - A dynamical "test-wave" model has been developed to study transport phenomena
      within oceanic internal wave fields. This model is extended here to describe
      effects of a mesoscale flow field on internal wave transport. Previous work with
      weak-interaction perturbation theory has suggested a substantial enhancement due
      to mesoscale currents. Extension to the strong-interaction regime in the present
      paper suggests a relatively small effect due to mesoscale interactions.

PMID- 16593279
TI  - At what wavelengths should we search for signals from extraterrestrial
      intelligence?
AB  - It has often been concluded that searches for extraterrestrial intelligence
      (SETI) should concentrate on attempts to receive signals in the microwave region,
      the argument being given that communication can occur there at minimum
      broadcasted power. Such a conclusion is shown to result only under a restricted
      set of assumptions. If generalized types of detection are considered-in
      particular, photon detection rather than linear detection alone-and if advantage
      is taken of the directivity of telescopes at short wavelengths, then somewhat
      less power is required for communication at infrared wavelengths than in the
      microwave region. Furthermore, a variety of parameters other than power alone may
      be chosen for optimization by an extraterrestrial civilization. Hence, while
      partially satisfying arguments may be given about optimal wavelengths for a
      search for signals from extraterrestrial intelligence, considerable uncertainty
      must remain.

PMID- 16593280
TI  - n-Type silicon photoelectrochemistry in methanol: Design of a 10.1% efficient
      semiconductor/liquid junction solar cell.
AB  - n-Type Si electrodes in MeOH solvent with 0.2 M (1-hydroxyethyl)ferrocene, 0.5 mM
      (1-hydroxyethyl)ferricenium, and 1.0 M LiClO(4) exhibit air mass 2 conversion
      efficiencies of 10.1% for optical energy into electricity. We observe open
      circuit voltages of 0.53 V and short-circuit quantum efficiencies for electron
      flow of nearly unity. The fill factor of the cell does not decline significantly
      with increases in light intensity, indicating substantial reduction in efficiency
      losses in MeOH solvent compared to previous nonaqueous n-Si systems. Matte etch
      texturing of the Si surface decreases surface reflectivity and increases
      photocurrent by 50% compared to shiny, polished Si samples. The high values of
      the open-circuit voltage observed are consistent with the presence of a thin
      oxide layer, as in a Schottky metal-insulator-semiconductor device, which yields
      decreased surface recombination and increased values of open-circuit voltage and
      short-circuit current. The n-Si system was shown to provide sustained
      photocurrent at air mass 2 levels (20 mA/cm(2)) for charge through the interface
      of >2,000 C/cm(2). The n-Si/MeOH system represents a liquid junction cell that
      has exceeded the 10% barrier for conversion of optical energy into electricity.

PMID- 16593281
TI  - Homological versus algebraic equivalence in a jacobian.
AB  - Let Z be an algebraic p cycle homologous to zero in an algebraic complex manifold
      V. Associated to Z is a linear function nu on holomorphic (2p + 1)-forms on V,
      modulo periods, that vanishes if Z is algebraically equivalent to zero in V. I
      give a formula for nu for the case of V the jacobian of an algebraic curve C and
      Z=C - C' (C' = "inverse" of C') in terms of iterated integrals of holomorphic 1
      forms on C. If C is the degree 4 Fermat curve, I use this formula to show that C 
      C' is not algebraically equivalent to zero.

PMID- 16593282
TI  - A physical interpretation for the natural photosynthetic process.
AB  - The efficiency of the process of photosynthesis is shown to depend on the
      molecular conversion of power. This requires establishment of a discipline that
      is now implicit in current thought and that offers a definition of relationship
      between equilibrium state and power. The quantum aspect for the microscopic
      process is different from the macroscopic system idealized as the heat engine and
      is required for the interpretation of molecular machinery. By using three
      postulates the ideal maximal efficiency for the molecular energy conversion is
      calculated from the data, which are assembled in the form of the "Z scheme" for
      photosynthesis. The observed and the calculated efficiencies for a green plant
      are substantially in agreement.

PMID- 16593283
TI  - Energetics of photosynthetic glow peaks.
AB  - By postulating temperature-dependent equilibria between two or more electron
      carriers acting as traps for electrons or holes, it is possible to modify the
      Randall-Wilkins theory of thermoluminescence so as to explain the abnormally
      large apparent activation energies and apparent frequency factors observed in
      photosynthetic glow curves when fitted by unmodified Randall-Wilkins theory. The
      equilibria serve to inhibit the formation of the light-emitting excited state by
      withholding the needed precursor state. When the inhibition is released at higher
      temperature by shift of equilibrium with temperature, the rise of the glow peak
      can be much faster than would result from Arrhenius behavior based on the true
      activation energy and so appears to correspond to a higher activation energy
      accompanied by a larger frequency factor. From another viewpoint, the enthalpy
      changes, DeltaH, of the equilibria tend to add to the activation energy.
      Similarly the entropy changes, DeltaS, of the equilibria tend to add to the
      entropy of activation, giving the large apparent frequency factors. The positive
      values of DeltaS needed would correspond to entropy decreases in the forward
      early electron transport. A comparison of the glow peaks obtained by different
      workers is also presented.

PMID- 16593284
TI  - Photosystem I reaction center from the thermophilic cyanobacterium Mastigocladus
      laminosus.
AB  - Photosystem I reaction center was isolated from the cyanobacterium Mastigocladus
      laminosus. It contained four different subunits with molecular masses (as
      determined by sodium dodecyl sulfate gels) of about 70,000 (subunit I), 16,000
      (subunit II), 11,000 (subunit III), and 10,000 (subunit IV) daltons. The purified
      reaction center contained about 100 chlorophyll a molecules per P(700); however,
      they could be readily depleted down to about 50 chlorophyll a per P(700) without
      loss in the photochemical activities. The reaction center was active in
      cytochrome c photooxidation, but the photooxidation of an acidic cytochrome, like
      the Euglena cytochrome 552, required the presence of cations. The purified
      reaction center was found to be similar in several respects to the photosystem I
      reaction centers from higher plants and, especially, to the one isolated from
      green algae. Subunit I appeared on sodium dodecyl sulfate gels in the same
      position and possessed the same shape of an apparent double band as the
      corresponding subunits I of green plants and of algae. Subunits I and II of
      photosystem I reaction centers from Mastigocladus, higher plants, and green algae
      showed immunological crossreactivity. This observation might serve as biochemical
      evidence for the common evolution of the photosystem I reaction centers. In
      higher plants and green algae subunit II is a product of cytoplasmic ribosomes
      and therefore, a high degree of homology should have been preserved upon transfer
      of its gene from the prokaryote to the nucleus of the eukaryotes.

PMID- 16593285
TI  - An Arabidopsis thaliana mutant defective in chloroplast dicarboxylate transport.
AB  - Reactions of the photorespiratory pathway of C(3) plants are found in three
      subcellular organelles. Transport processes are, therefore, particularly
      important for maintaining the uninterrupted flow of carbon through this pathway.
      We describe here the isolation and characterization of a photorespiratory mutant
      of Arabidopsis thaliana defective in chloroplast dicarboxylate transport. Genetic
      analysis indicates the defect is due to a simple, recessive, nuclear mutation.
      Glutamine and inorganic phosphate transport are unaffected by the mutation. Thus,
      in contrast to previous reports for pea and spinach, glutamine uptake by
      Arabidopsis chloroplasts is mediated by a transporter distinct from the
      dicarboxylate transporter. Both the inviability and the disruption of amino-group
      metabolism of the mutant under photorespiratory conditions suggest that the
      primary function of the dicarboxylate transporter in vivo is the transfer of 2
      oxoglutarate and glutamate across the chloroplast envelope in conjunction with
      photorespiratory nitrogen metabolism. The role commonly ascribed to this
      transporter, conducting malate-aspartate exchanges for the indirect export of
      reducing equivalents from the chloroplast, appears to be a minor one.

PMID- 16593286
TI  - Environmental controls on stomatal conductance in a shrub of the humid tropics.
AB  - Leaves of Piper hispidum, a shrub native to the lowland tropics of Mexico, have a
      strong stomatal response to humidity that results in similar rates of water loss
      under a wide range of leaf-to-air water-vapor concentration gradients. Stomatal
      conductance of these leaves is insensitive to CO(2) concentration and increases
      in response to high humidity even in the dark.

PMID- 16593287
TI  - Hawkmoth pollination of Mirabilis longiflora (Nyctaginaceae).
AB  - A guild composed of very-long-tubed hawkmoth flowers (nectar tubes, 9 cm or more
      long), belonging to different genera and families, occurs in the American
      Southwest. Our knowledge of the hawkmoth associates of these flowers is
      fragmentary. Mirabilis longiflora, a member of the guild with a tube 10.0-10.5 cm
      long, was found to be visited and pollinated mainly by Manduca quinquemaculata
      with a proboscis 10.7-11.6 cm long in the Chiricahua Mountains of southeastern
      Arizona. This example fits in with four other previously reported cases. The long
      tongued Man. quinquemaculata is now known to be associated with five species of
      very long-tongued hawkmoth flowers in the Southwest, and Man. rustica has been
      found on one of them.

PMID- 16593288
TI  - The periseptal annulus: An organelle associated with cell division in Gram
      negative bacteria.
AB  - Evidence is presented that the site of cell division in Salmonella typhimurium is
      flanked by two circumferential zones of cell envelope differentiation, the
      periseptal annuli, which separate the division site from the remainder of the
      cell envelope. Each annulus is composed of a continuous structure in which the
      membranous elements of the cell envelope are closely associated with the murein
      cytoskeleton. The paired annuli appear early in the division process and the
      region between them defines a new cellular domain, the periseptal compartment,
      within which the division septum is formed.

PMID- 16593289
TI  - Optimal sequence alignments.
AB  - Current theory is adequate to the task of finding an optimal alignment between
      two character strings such as nucleic acids. Most algorithms currently in use
      must fail to find the homologous alignment between a set of codons for the
      chicken alpha- and beta-hemoglobin sequence when it is in fact discoverable by a
      more general treatment of gaps. Fundamental reasons for this are discussed.

PMID- 16593290
TI  - Developmental cell interactions in Myxococcus xanthus and the spoC locus.
AB  - The product(s) of the Myxococcus xanthus spoC locus is required for two
      multicellular activities in fruiting body development, rippling and sporulation.
      Ripples, which are formed early in development, are spatially separated ridges of
      cells that move synchronously. Myxospores are heat-resistant resting cells that
      are formed near the end of the developmental process. To investigate the function
      of spoC, it was cloned in an Escherichia coli plasmid, then transferred to M.
      xanthus by specialized transduction with coliphage P1. The plasmid, which cannot
      replicate in M. xanthus, integrated into the M. xanthus chromosome, producing two
      copies of the spoC locus in tandem. Cells containing one copy of a mutant allele
      and one copy of the wild-type allele displayed the wild-type phenotype. Cells
      containing two different mutant alleles failed to ripple or sporulate, implying
      that all four independent spoC mutations are in the same gene or unit of
      transcription. Homozygous mutant duplications arose from constructions in which
      DNA from a spo(+) donor was transduced into a spoC recipient, or vice versa, at
      an average frequency of 14%, indicating that gene conversion was a frequent
      event.

PMID- 16593291
TI  - Bacterio-opsin mutants of Halobacterium halobium.
AB  - The bacterio-opsin (bop) gene of Halobacterium halobium R1 has been cloned with
      about 40 kilobases of flanking genomic sequence. The 40-kilobase segment is
      derived from the (G+C)-rich fraction of the chromosome and is not homologous to
      the major (pHH1) or minor endogenous covalently closed circular DNA species of H.
      halobium. A 5.1-kilobase Pst I fragment containing the bop gene was subcloned in
      pBR322 and a partial restriction map was determined. Defined restriction
      fragments of this clone were used as probes to analyze the defects associated
      with the bop gene in 12 bacterio-opsin mutants. Eleven out of 12 of the mutants
      examined had inserts ranging from 350 to 3,000 base pairs either in the bop gene
      or up to 1,400 base pairs upstream. The positions of the inserts were localized
      to four regions in the 5.1-kilobase genomic fragment: within the gene (one
      mutant), in a region that overlaps the 5' end of the gene (seven mutants), and in
      two different upstream regions (three mutants). Two revertants of the mutant with
      the most distal insert had an additional insert in the same region. The polar
      effects of these inserts are discussed in terms of inactivation of a regulatory
      gene or disruption of part of a coordinately expressed operon. Given the defined
      nature of the bop mRNA-i.e., it has a 5' leader sequence of three ribonucleotides
      these observations indicate that the bop mRNA might be processed from a large
      mRNA transcript.

PMID- 16593292
TI  - Reciprocal and nonreciprocal recombination in diploid clones from Bacillus
      subtilis protoplast fusion: Association with the replication origin and terminus.
AB  - The primary heterodiploid bacteria regenerated after Bacillus subtilis fusion,
      although generally noncomplementing diploids, behave in pedigree analysis as
      multipotential systems. Individual diploid colonies yielding complete reciprocal
      recombinant (RR) progeny-often accompanied by one or both parents-constitute 10
      30% of the total recombinant-forming units. The RR (reciprocal for 8-11 genes)
      usually occur in equivalent numbers both among and within individual colonies.
      Novel for bacteria, they demonstrate that entire parental genomes brought
      together within a diploid protoplast are retained as two independent replicons
      able to undergo classical recombination characteristic of eukaryotic
      gametogenesis. Parental or recombinant genomes are also subject to multiple
      rounds of recombination without obligate segregation and often not reciprocal.
      Diploid recombinant clones, sharing streptomycin resistance but reciprocal for
      auxotrophic markers, have displayed a partial ability to make a facultative shift
      in chromosome expression. They have also produced two types of prototrophs: a
      stable one (presumably haploid and recombinant) and an unstable one, (diploid and
      temporarily complementing at low frequency). It follows that chromosome
      extinction may affect both parental and recombinant chromosomes and does not
      interfere with recombination. Analysis of the number and chromosomal distribution
      of crossovers in all recombinants and those from single diploid clones shows
      increased frequency of exchange in the regions of the replication origin and
      terminus, possibly a result of the association of these sites with the cell wall
      or membrane.

PMID- 16593293
TI  - Population trends in China and India (A Review).

PMID- 16593294
TI  - Magellanic cloud planetary nebula with suspected strong forbidden iron lines.
AB  - The relatively high-excitation nebula (Westerlund-Smith object 25) in the large
      Magellanic cloud shows prominent forbidden lines of [Ar IV], the close [Ne IV]
      pair lambda4724, 4726, [Ca V] lambda5309, [Fe V] lambda4227, and probably [Fe VI]
      and [Fe VII], as well. A conventional interpretation of observations secured with
      a vidicon detector at the Cerro Tololo 4-m telescopes indicates an essentially
      "normal" helium abundance but depletions of N, O, Ne, and other elements with
      respect to our own galaxy. When a comparison is made with diffuse nebulae or H II
      regions in the large Magellanic cloud, we find helium to be more abundant, oxygen
      to be depleted, and nitrogen, neon, and argon to be comparable. The abundance of
      sulfur is uncertain. Iron in the gaseous phase is certainly more plentiful than
      in conventional planetaries.

PMID- 16593295
TI  - Mechanism of four-level laser action in solution excimer and excited-state proton
      transfer cases.
AB  - Four-level laser energy level schemes are compared from the mechanistic
      spectroscopic viewpoint: (i) noble-gas excimer, (ii) solution molecular excimer,
      (iii) conventional dye laser, and (iv) intramolecular proton transfer. The lasing
      action of the chlorophyll special pair is discussed as an example of a solution
      excimer laser, and the lasing action of 3-hydroxyflavone and other molecules is
      discussed as an example of an intramolecular proton-transfer laser.

PMID- 16593296
TI  - Degree of mapping for nonlinear mappings of monotone type.
AB  - A classical degree function is constructed for pseudomonotone mappings from a
      reflexive Banach space to its dual, using Galerkin approximations. This
      generalizes the Leray-Schauder degree when the Banach space is a Hilbert space
      and yields a flexible analytical tool for the study of nonlinear elliptic
      problems of higher order in divergence form.

PMID- 16593297
TI  - Laws of composition of Backlund transformations and the universal form of
      completely integrable systems in dimensions two and three.
AB  - Backlund transformations are defined as operations on solutions of a Riemann
      boundary value problem (vector bundles over P(1)) that add apparent
      singularities. For solutions of difference and differential linear spectral
      problems, Backlund transformations are presented in explicit form through the
      Christoffel formula and its generalizations. Identities satisfied by iterations
      of elementary Backlund transformations are represented in the form of the law of
      addition or as the three-dimensional difference equation of Hirota's type. Matrix
      two-dimensional isospectral deformation equations are imbedded into three
      dimensional scalar systems of Kadomtzev-Petviashvili (law of addition) form. Two
      dimensional matrix systems correspond to reductions of Kadomtzev-Petviashvili
      equations with pseudodifferential operators satisfying algebraic equations.

PMID- 16593298
TI  - Infinite flag varieties and conjugacy theorems.
AB  - We study the orbit of a highest-weight vector in an integrable highest-weight
      module of the group G associated to a Kac-Moody algebra [unk](A). We obtain
      applications to the geometric structure of the associated flag varieties and to
      the algebraic structure of [unk](A). In particular, we prove conjugacy theorems
      for Cartan and Borel subalgebras of [unk](A), so that the Cartan matrix A is an
      invariant of [unk](A).

PMID- 16593299
TI  - Equivalence of partition properties and determinacy.
AB  - It is shown that, within L(R), the smallest inner model of set theory containing
      the reals, the axiom of determinacy is equivalent to the existence of arbitrarily
      large cardinals below Theta with the strong partition property kappa -->
      (kappa)(kappa).

PMID- 16593300
TI  - Isolation and sequence of the gene for the large subunit of ribulose-1,5
      bisphosphate carboxylase from the cyanobacterium Anabaena 7120.
AB  - Cloned DNA probes containing genes coding for the large subunit of ribulose-1,5
      bisphosphate carboxylase (rbcA) of corn and of Chlamydomonas were used to
      identify, by heterologous hybridization, DNA fragments from Anabaena 7120
      carrying the corresponding gene sequence. The same probes were used to isolate,
      from a recombinant lambda library, a 17-kilobase-pair EcoRI Anabaena DNA fragment
      containing the coding sequence for the rbcA gene. The entire coding sequence, as
      well as 210 base pairs of 5' flanking region and 210 base pairs of 3' flanking
      region, was determined. Comparison of the nucleotide and amino acid sequences
      with those of corn, spinach, Chlamydomonas, and Synechococcus rbcA genes revealed
      homology of 71-77% at the nucleotide level and 80-85% at the amino acid level.
      Conservation of sequence is lost immediately outside the coding region on either
      side. Codon usage in the Anabaena rbcA gene is not significantly different from
      that in the Anabaena genes for nitrogenase reductase and nitrogenase beta
      subunit.

PMID- 16593301
TI  - Complete nucleotide sequence of a French bean storage protein gene: Phaseolin.
AB  - The complete nucleotide sequences of the gene and the mRNA coding for a specific
      phaseolin type French bean major storage protein have been determined. Comparison
      of these sequences reveals a phaseolin gene structure consisting of 80 base pairs
      (bp) of 5' untranslated DNA, 1,263 bp of protein-encoding DNA which is
      interrupted by five intervening sequences (IVS1, 72 bp; IVS2, 88 bp; IVS3, 124
      bp; IVS4, 128 bp; and IVS5, 103 bp), and 135 bp of 3' untranslated DNA. Sequences
      characteristic of eukaryotic promoters "CCAAT" and "TATA" are present in the 5'
      flanking DNA, and the eukaryotic poly(A) addition signal A-A-T-A-A-A occurs 16 bp
      before the first nucleotide of poly(A). The derived amino acid sequence yields an
      amino acid composition and a molecular weight compatible with those found for the
      beta-type phaseolin protein. Two regions that probably serve as carbohydrate
      peptide linkage recognition sites have been identified. A region of highly
      hydrophobic amino acids at the NH(2) terminus of the protein suggests the
      presence of a signal peptide in the newly synthesized phaseolin protein.

PMID- 16593302
TI  - Extrachromosomal DNA of pea (Pisum sativum) root-tip cells replicates by strand
      displacement.
AB  - In cultured pea roots there is extrachromosomal DNA associated with cells that
      differentiate from the G(2) phase of the cell cycle that is absent from those
      that differentiate from the G(1) phase. We examined this extrachromosomal DNA by
      electron microscopy and found that it consisted of three types: (i) double
      stranded linear molecules with single-stranded branches (74%), (ii) double
      stranded molecules without branches (26%), and (iii) free single-stranded
      molecules. The double-stranded molecules with or without branches were similar in
      length, having a modal length of 10-15 mum. The free single-stranded molecules
      were shorter and had a mean length of 3.8 mum. The length of the branches
      attached to the duplex molecules was only slightly less than that of the free
      form. The duplex molecules with branches were interpreted as configurations
      reflecting an ongoing strand-displacement process that results in free single
      stranded molecules. Finally, measurements on duplex molecules with multiple
      branches suggested that the extrachromosomal DNA may exist in the form of
      tandemly repeated sequences.

PMID- 16593303
TI  - Alloprocoptic selection: A mode of natural selection promoting polymorphism.
AB  - The fitness effect of genetic variation at three loci coding for enzymes is
      studied in Drosophila melanogaster. The fertility of a female is determined by
      the female genotype as well as by the genotype of the male with which she mates.
      Significant interactions exist between female and male genotype, so that the
      fertility of a given mating combination cannot be predicted from the average
      fertility of the two genotypes involved. Multiple stable equilibria are possible
      when such interactions exist. At two loci, the fertility is greater than expected
      when the two mating individuals are homozygous for different alleles and smaller
      than expected when they are homozygous for the same allele. This mode of
      selection in which association of opposites increases their fitness is herein
      named alloprocoptic selection. It will contribute to maintaining genetic
      polymorphism in nature.

PMID- 16593304
TI  - Uridine diphosphate glucose breakdown is mediated by a unique enzyme activated by
      fructose 2,6-bisphosphate in Solanum tuberosum.
AB  - In the presence of inorganic phosphate, uridine 5'-diphosphate glucose (UDPG) is
      specifically hydrolyzed to glucose 1-phosphate and UDP by a unique enzyme, UDPG
      phosphorylase. The activity of the enzyme was maximally stimulated by fructose
      2,6-bisphosphate, a regulatory metabolite recently discovered in both plants and
      animals, and by 2-phosphoglyceric acid. At 1 muM, fructose 2,6-bisphosphate
      stimulated UDPG phosphorolysis 10-fold, whereas 2-phosphoglyceric acid was
      required at higher concentrations (100 muM) to produce a similar effect. Fructose
      2,6-bisphosphate appears to increase the affinity of the enzyme for inorganic
      phosphate, with a change in K(m) from 1.6 mM to 0.3 mM. The results suggest that
      fructose 2,6-bisphosphate participates in the regulation of other pathways of
      carbohydrate metabolism in addition to playing its recognized role in glycolysis
      and gluconeogenesis.

PMID- 16593305
TI  - Theory of measurement of Forster-type energy transfer in macromolecules.
AB  - We describe the theoretical basis of an unconventional method for the
      determination of the amount of energy transferred between two fluorophores by the
      Forster mechanism. The method involves an internal comparison made by separation
      of the fluorophores in situ (i.e., in the optical cell), for example, by means of
      enzymic digestion; it eliminates several important sources of error and it
      simplifies calculation while making maximal use of the information contained in
      the fluorescence spectra. The validity of the method is demonstrated by
      determination of the known distance between two modifiable sites on the transfer
      RNA molecule, and its usefulness is exemplified by its application to
      triangulation of the ribosome of Escherichia coli.

PMID- 16593306
TI  - Derivation of the relation between the linear Onsager coefficients and the
      equilibrium one-way cycle fluxes of a biochemical kinetic diagram.
AB  - The Onsager flux-force coefficients L(ij) for any biochemical system at a steady
      state near equilibrium have a simple interpretation: they are linear combinations
      of the equilibrium one-way cycle fluxes of the kinetic diagram for the system. An
      explicit and general expression for L(ij) is derived. This supplements the more
      pedagogical argument published elsewhere, which was based on a particular special
      case.

PMID- 16593307
TI  - UV-induction of chalcone synthase mRNA in cell suspension cultures of
      Petroselinum hortense.
AB  - DNAs complementary to poly(A)(+) mRNAs from UV-irradiated cell suspension
      cultures of parsley (Petroselinum hortense) were inserted into pBR322 and used to
      transform Escherichia coli strain RR1. A clone containing a DNA complementary to
      chalcone synthase mRNA was identified by hybrid-selected and hybrid-arrested
      translation. Large and rapid changes in the amount of chalcone synthase mRNA in
      response to irradiation of the cells was detected by RNA blot hybridization
      experiments. The pattern of changes coincided with that previously determined for
      the rate of chalcone synthase synthesis as measured either in vivo or with
      polyribosomal mRNA in vitro. The results are consistent with the hypothesis that
      induction of chalcone synthase by UV light is due to a transient increase in the
      rate of synthesis of chalcone synthase mRNA.

PMID- 16593308
TI  - Soybean nodulin genes: Analysis of cDNA clones reveals several major tissue
      specific sequences in nitrogen-fixing root nodules.
AB  - Plant gene products that could play a role in the process of symbiotic nitrogen
      fixation in leguminous plants were detected by screening a cDNA library prepared
      from soybean nodule poly(A)(+) RNA. About 13% of the 5,700 clones screened
      contained sequences detectable with a root cDNA probe while about 2,100 clones
      (37% of the library) contained sequences that were detectable only with nodule
      cDNA. Five unique sequence species, accounting for more than half of the 2,100
      nodule-specific clones, were identified by cross-hybridization experiments. The
      most abundant species, represented by 860 clones, encodes the well-characterized
      protein, leghemoglobin (Lb). The other four species, designated NodA, NodB, NodC,
      and NodD, are represented by 350, 55, 61, and 6 clones, respectively. Each of
      these four species was found to be encoded by the plant nuclear genome at low
      copy number. The transcripts corresponding to the nodule-specific clones
      represented 12-15% (Lb), 6% (NodA), and 0.5-1.1% (NodB, NodC, and NodD) mole
      fraction of nodule polysomal mRNAs but could not be detected in root polysomal
      RNA. Hybrid-selection of nodule mRNAs by representative clones and in vitro
      translation indicated that polypeptides of M(r) 44,000, 27,000, 24,000, and
      100,000-120,000 are encoded by NodA, NodB, NodC, and NodD sequences,
      respectively. These polypeptides reacted with antiserum prepared against total
      soluble nodule proteins suggesting that the cloned sequences encode nodule
      specific proteins, nodulins.

PMID- 16593309
TI  - Studies of osmoregulation in salt adaptation of cyanobacteria with ESR spin-probe
      techniques.
AB  - Sucrose is accumulated in response to NaCl-induced stress in the cyanobacterium
      Synechococcus 6311. Internal cell volume was measured by ESR spectra with 2,2,6,6
      tetramethyl-4-oxopiperidinoxy free radical (TEMPONE) as a spin probe in order to
      calculate sucrose concentrations inside the cell. This method is rapid and
      reliable and provides an unambiguous measurement of absolute volumes in different
      osmotic environments. Because the osmolar concentration of sucrose does not
      counter-balance the osmolar concentrations of ions in the growth medium, we
      suggest that sucrose accumulation is one of the mechanisms involved in the
      process of adaptation to salt of Synechococcus 6311. The accumulation of sucrose
      in non-N(2)-fixing cyanobacteria such as Synechococcus 6311 and in N(2)-fixing
      cyanobacteria such as Nostoc muscorum suggests a common mechanism of
      osmoregulation of fresh water cyanobacteria in response to increasing NaCl
      concentrations in the growth medium.

PMID- 16593310
TI  - Rapid degradation of unassembled ribulose 1,5-bisphosphate carboxylase small
      subunits in chloroplasts.
AB  - We have detected a proteolytic mechanism in chloroplasts that selectively and
      rapidly degrades the imported small subunit of ribulose 1,5-bisphosphate
      carboxylase when pools of the chloroplast-synthesized large subunit are depleted.
      This degradation system is constitutively present and appears to be responsible
      for precise stoichiometric accumulation of the two subunits of the enzyme. We
      believe similar proteolytic mechanisms participate in regulating the accumulation
      of other photosynthetic proteins during chloroplast biogenesis.

PMID- 16593311
TI  - Coordinate gene expression during somatic embryogenesis in carrots.
AB  - There are several biochemical differences between the callus and the embryos of
      carrot culture. Callus tissue produces callus-specific proteins and a
      conditioning factor that is necessary for the synthesis of callus-specific
      proteins. By contrast, embryos produce embryo-specific proteins [Sung, Z. R. &
      Okimoto, R. (1981) Proc. Natl. Acad. Sci. USA 78, 3683-3687] and develop the
      capability to inactivate cycloheximide [Sung, Z. R., Lazar, G. J. & Dudits, D.
      (1981) Plant Physiol. 68, 261-264]. A mutant, WCH105, that can inactivate
      cycloheximide in the callus as well as in the embryos produces the embryo
      specific proteins instead of the callus-specific proteins and fails to produce
      the conditioning factor by the callus tissue. Callus tissues also produce a
      conditioning factor for callus growth. This factor is not the same as the
      conditioning factor for the synthesis of the callus-specific proteins, as WCH105
      can grow as callus. The existence of WCH105 demonstrates that the callus-specific
      and embryo-specific traits are coordinately regulated, but in an opposite manner.
      A common mechanism apparently activates one set and inactivates the other set of
      functions. WCH105 seems to be impaired in this mechanism.

PMID- 16593312
TI  - When does the good of the group override the advantage of the individual?
AB  - In a system of N populations of n reproductive individuals apiece, in which each
      population has constant variance v(2) and lasts L generations, group selection on
      a quantitative character has a reasonable chance of overriding selection within
      populations if (and only if) the populations never exchange migrants, each
      population is founded by colonists from a single parent population, and the
      number of populations exceeds the effective number of reproductive individuals
      per population. If each population derives from a single parent population, then
      the exchange of a single successful migrant per population per L generations can
      triple the strength of group selection required to overcome a given selection
      within populations. If populations exchange no migrants, then the derivation of
      one in every N populations from two equally represented parents (while the others
      all derive from a single parent) doubles the strength of group selection required
      to prevail. Group selection is accordingly likely to be effective only in certain
      categories of parasites.

PMID- 16593313
TI  - Organization and expression of Rhizobium meliloti nitrogen fixation genes.
AB  - The boundaries of a nif gene cluster in Rhizobium meliloti were determined by Tn5
      mutagenesis. These genes are clustered within a 14- to 15-kilobase (kb) region
      that includes the nitrogenase structural genes. Sequences within 10 kb on either
      side of this region are devoid of symbiotically essential gene function. RNA blot
      analysis identified a 5- to 6-kb transcript that corresponds to the nitrogenase
      structural gene operon. The 5' end of this transcript and its polarity were
      determined by nuclease S1 mapping. The 5' end of another nif transcript was also
      identified by nuclease S1 mapping. The promoter regions for these two nif
      transcripts control transcription in divergent directions and are separated by
      1.9 kb of symbiotically unessential DNA. One Tn5 insertion within the nitrogenase
      operon did not create a polar mutation. The implications of this finding and the
      overall emerging picture of the genetic organization of this nif region are
      discussed.

PMID- 16593314
TI  - Differential methylation of chloroplast DNA regulates maternal inheritance in a
      methylated mutant of Chlamydomonas.
AB  - In Chlamydomonas, the maternal inheritance of chloroplast genes correlates with
      the differential methylation of chloroplast DNA (chlDNA) in females (mt(+)) but
      not in males (mt(-)). Our previous studies have supported our methylation
      restriction model in which the maternal transmission is accounted for by the
      differential methylation in gametes which protects female but not male chlDNA
      from degradation during zygote formation. In the mutant me-1 [Bolen, P. L.,
      Grant, D. M., Swinton, D., Boynton, J. E. & Gillham, N. W. (1982) Cell 28, 335
      343], chlDNA of vegetative cells of both mating types is heavily methylated even
      before gametogenesis; nonetheless, maternal inheritance occurs in mutants as in
      wild type. To investigate the mechanism of maternal inheritance in the me-1
      mutant, we have compared restriction fragment patterns after agarose gel
      electrophoresis of chlDNAs from mutant vegetative cells and gametes with those
      from wild type, by using a set of 32 restriction enzymes of which 17 were
      methylation-sensitive in this system. We find that additional methylation occurs
      during gametogenesis in the mutant female (mt(+)) but not in the corresponding
      male (mt(-)). Thus, gamete-specific, mating-type-specific methylation occurs in
      the me-1 mutant as in the wild type, consistent with our methylation-restriction
      model. In the me-1 mutant, gametic methylation occurs on a background of
      vegetative cell methylation not present in wild-type cells and irrelevant to the
      regulation of chloroplast inheritance. Comparison of the me-1 mutation with the
      mat-1 mutation [Sager, R., Grabowy, C. & Sano, H. (1981) Cell 24, 41-47] provides
      evidence for the existence of two different chlDNA methylation control systems:
      mat-1, linked to the mating type locus and regulating the mating-type-specific
      methylation that correlates with maternal inheritance, and me-1, unlinked to the
      mating type locus and unrelated to the regulation of maternal inheritance.

PMID- 16593315
TI  - Sequence alignments in the neighborhood of the optimum with general application
      to dynamic programming.
AB  - When applying dynamic programming techniques to obtain optimal sequence
      alignments, a set of weights must be assigned to mismatches, insertion/deletions,
      etc. These weights are not predetermined, although efforts are being made to
      deduce biologically meaningful values from data. In addition, there are sometimes
      unknown constraints on the sequences that cause the "true" alignment to disagree
      with the optimum (computer) solution. To assist in overcoming these difficulties,
      an algorithm has been developed to produce all alignments within a specified
      distance of the optimum. The distance can be chosen after the optimum is
      computed, and the algorithm can be repeated at will. Earlier algorithms to solve
      this problem were very complex and not practical for any case involving sequences
      with significant time or storage requirements. The algorithm presented here
      overcomes these difficulties and has application to general, discrete dynamic
      programming problems.

PMID- 16593316
TI  - Self-similar self-avoiding structures: Models for polymers.
AB  - The hierarchy of m,n-self-similar self-avoiding structures on a lattice is
      introduced as a model for linear and branched polymers. The self-similarity
      condition permits exact solutions that use a generating-function renormalization
      procedure with full accounting for volume exclusion. Illustrative results are
      given for the 1,2-linear-chain model and for the 1,2-branched-structure model on
      a honeycomb lattice. Exponents for the dependence of polymer size on monomer
      number are obtained for these models, with that for branched structures being
      independent of the (nonzero) fraction of branch points. Exponents also are found
      involving branching probability and branching activity; the fact that those
      quantities are found to be distinct even in the dilute branching limit is a
      manifestation of the long-range nature of the excluded volume interaction.

PMID- 16593317
TI  - Multielectron storage and hydrogen generation with colloidal semiconductors.
AB  - Multielectron storage and hydrogen generation by light is achieved in aqueous
      dispersions of ultrafine TiO(2) particles (120-A diameter) when the amphiphilic
      viologen derivative N-tetradecyl-N'-methyl-4,4'-dipyridinium dichloride
      (C(14)MV(2+)) is used as an electron relay. Consecutive reduction of C(14)MV(2+)
      to the radical ion (C(14)MV(+)) and neutral (C(14)MV(0)) was observed after band
      gap excitation of the semiconductor particle. Through surface adsorption of the
      relay, these electron-transfer reactions can occur very rapidly and are completed
      within less than 100 musec (pH 11). Two-electron reduction of C(14)MV(2+) can be
      coupled with H(2) generation in alkaline medium in the presence of Pt catalyst
      codeposited onto the TiO(2) particle. Electron-relay-free systems are 1/15th as
      efficient in producing H(2) at the same pH.

PMID- 16593319
TI  - L(2) Cohomology of the Bergman metric.
AB  - The L(2) cohomology of the Bergman metric is infinite dimensional in the middle
      degree and vanishes for all other degrees. Asymptotic expansions are given for
      the Schwartz kernels of the corresponding projections onto harmonic forms.

PMID- 16593318
TI  - Critique of a proposed stability criterion for chemical systems far from
      equilibrium.
AB  - Noyes [Noyes, R. M. (1981) Proc. Natl. Acad. Sci. USA 78, 7248-7249] has obtained
      a result for the Gibbs free energy per unit mass in a continuous flow stirred
      tank reactor, which states that the steady-state free energy increases
      monotonically with decreasing residence time for any stable stationary point. We
      show that his derivation is based on an erroneous stability criterion. We further
      investigate the dependence of the Gibbs free energy on residence time for the
      case of mass-action kinetics and ideal mixtures. We then apply this development
      to Schlogl's trimolecular reaction mechanism [Schlogl, F. (1971) Z. Phys. 248,
      446-458] and show that Noyes' conjecture is violated for this simple example.

PMID- 16593320
TI  - Rational approximations to linear forms of exponentials and binomials.
AB  - Mahler proved the following quantitative result supplementing the Lindemann
      Weierstrass theorem: Sigma(i=0) (n)C(i)e(ri) > H(-n-epsilon) for any distinct
      rational numbers r(0),r(1),..., r(n) and rational integers C(0),C(1),...,C(n)
      with H = max(0</=i</=n) C(i). We improve Mahler's estimate by replacing
      exponentials e(ri) by linearly independent linear forms L(i) = Sigma L(ij)e(sij)
      with rational L(ij),s(ij)i = 0,1,...,n. Similar results are obtained for
      binomials (a/b)(ri) or Sigma L(ij)(a/b)(sij) with integers a,b and logb/loga > 1 
      epsilon. The simplest examples of new numbers with the irrationality exponent "2
      + epsilon" are sinh 1 or sin 1.

PMID- 16593321
TI  - Olfactory receptors in the melon fly Dacus cucurbitae and the oriental fruit fly
      Dacus dorsalis.
AB  - Male melon flies (Dacus cucurbitae) from a colony in Hawaii were evaluated for
      limit of response to the olfactory stimulant raspberry ketone and to more than 40
      related molecules. The results were compared with the limits of response of
      oriental fruit flies (Dacus dorsalis) under identical conditions. The nature of
      the response of the two species to attractive compounds appeared to be identical
      with regard to orientation, searching, pulsating mouthparts, and compulsive
      feeding. However, there was very little overlap in the response of the two
      species to phenylpropanoid-type compounds. D. cucurbitae responded most strongly
      to p-hydroxyphenylpropanoids while D. dorsalis responded most strongly to 3,4
      dimethoxyphenylpropanoids. The results are discussed in terms of antennal
      receptor site geometry and with regard to the coevolution of two major groups of
      Dacini with plant kairomones.

PMID- 16593322
TI  - Evidence for metabolic and functional discrimination of sterols by Phytophthora
      cactorum.
AB  - When fed 10 ppm of one of the following sterols: cholesterol (cholest-5-en-3beta
      ol), wingsterol (21-isopentylcholesterol), desmosterol [cholesta-5,24(25)-dien
      3beta-ol], 24-methylenecholesterol [ergosta-5,24(28)-dien-3beta-ol], or
      fucosterol [stigmasta-5,24(28)-dien-3beta-ol], the pathogenic fungus Phytophthora
      cactorum, which is naturally unable to epoxidize squalene, accumulated each of
      the test compounds to similar levels. Fucosterol, the only sterol metabolized,
      was reduced to yield 24-ethylcholesterol. All the sterols tested induced the
      formation of sex structures. Fertilization and subsequent maturation of oospores
      capable of germination occurred only with the naturally occurring sterols.
      Wingsterol treatments resulted in aborted oospores. None of the sterols tested
      was inhibitory to growth, measured as changes in the 21-day mycelial dry weight.
      The results are consistent with the view that the accumulated sterol functions to
      regulate the life cycle of P. cactorum. However, the metabolism and kinds of
      recognition of the sterol molecule, in terms of uptake and effects on growth and
      induction of the various sexual events, contrast sharply with what is known for
      other oomycetous fungi such as Achlya and Saprolegnia. This implies that the
      evolutionary histories of the Oomycetes may be different.

PMID- 16593323
TI  - Cytoplasmic and chloroplast synthesis of phycobilisome polypeptides.
AB  - In vivo labeling of eukaryotic phycobilisomes in the presence of inhibitors of
      translation on 70S and 80S ribosomes demonstrates that some of the polypeptides
      of this light-harvesting complex are synthesized in the cytoplasm while others
      are synthesized in the chloroplast. The major pigmented polypeptides, the alpha
      and beta subunits of the biliproteins (molecular weights between 15,000 and
      20,000) and the anchor protein (molecular weight about 90,000) are translated on
      70S ribosomes. This suggests that these polypeptides are made within the algal
      chloroplast. Because the alpha and beta subunits comprise a group of closely
      related polypeptides, the genes encoding these polypeptides may reside in the
      plastid genome as a multigene family. Other prominent phycobilisome polypeptides,
      including a nonpigmented polypeptide that may be involved in maintaining the
      structural integrity of the complex, are synthesized on cytoplasmic ribosomes.
      Because the synthesis of phycobilisomes appears to require the expression of
      genes in two subcellular compartments, this system may be an excellent model for:
      (i) examining interaction between nuclear and plastid genomes: (ii) elucidating
      the molecular processes involved in the evolution of plastid genes: (iii)
      clarifying the events in the synthesis and assembly of macromolecular complexes
      in the chloroplast.

PMID- 16593324
TI  - Translational regulation of a specific gene during oogenesis and embryogenesis of
      Drosophila.
AB  - Polysomal and postpolysomal mRNAs were prepared from Drosophila egg chambers or
      embryos of different developmental stages. Cell-free translation of these mRNAs
      followed by two-dimensional gel electrophoresis of the products indicated the
      presence of a specific mRNA that appears to be translated (polysome-associated)
      during oogenesis. This mRNA, designated T1 mRNA, is selectively excluded from
      polysomes in 3-hr- and 5-hr-old embryos and is again translated in 18-hr-old
      embryos. A clone containing DNA complementary to T1 mRNA was selected from a
      library of recombinant DNA prepared from polyadenylylated ovary RNA. This clone
      was positively identified by hybrid-selected translation followed by two
      dimensional gel electrophoresis and autoradiography. T1 mRNA is polyadenylylated
      and codes for a small, acidic protein. The cloned probe hybridizes to a unique
      site (2L-39CD) of the polytene chromosomes, very close to the histone genes. The
      results suggest that this mRNA is under specific translational regulation in
      contrast to a background of a large number of other abundant mRNAs that are
      translated at all developmental stages examined.

PMID- 16593325
TI  - Spider leg autotomy induced by prey venom injection: An adaptive response to
      "pain"?
AB  - Field observations showed orb-weaving spiders (Argiope spp.) to undergo leg
      autotomy if they are stung in a leg by venomous insect prey (Phymata fasciata).
      The response occurs within seconds, before the venom can take lethal action by
      spread to the body of the spiders. Autotomy is induced also by honeybee venom and
      wasp venom, as well as by several venom components (serotonin, histamine,
      phospholipase A(2), melittin) known to be responsible for the pain
      characteristically elicited by venom injection in humans. The sensing mechanism
      by which spiders detect injected harmful chemicals such as venoms therefore may
      be fundamentally similar to the one in humans that is coupled with the perception
      of pain.

PMID- 16593326
TI  - A short 5' flanking region containing conserved sequences is required for
      silkworm alanine tRNA gene activity.
AB  - Using partially deleted genes, we have identified an upstream control signal
      required for transcription of a Bombyx mori (silkworm) tRNA(2) (Ala) gene. The 5'
      boundary of this essential region lies between 34 and 11 nucleotides preceding
      the transcription initiation site. Sequences in the 5' half of the tRNA(2) (Ala)
      coding region are also important. Both regions contain oligonucleotides that are
      conserved among several Bombyx genes transcribed by RNA polymerase III,
      suggesting that these sequences may have a general control function.

PMID- 16593327
TI  - Similarity principles for the biology of pelagic animals.
AB  - A similarity principle is formulated according to which the statistical pattern
      of the pelagic population is identical in all scales sufficiently large in
      comparison with the molecular one. From this principle, a power law is obtained
      analytically for the pelagic animal biomass distribution over the animal sizes. A
      hypothesis is presented according to which, under fixed external conditions, the
      oxygen exchange intensity of an animal is governed only by its mass and density
      and by the specific absorbing capacity of the animal's respiratory organ. From
      this hypothesis a power law is obtained by the method of dimensional analysis for
      the exchange intensity mass dependence. The known empirical values of the
      exponent of this power law are interpreted as an indication that the oxygen
      absorbing organs of the animals can be represented as so-called fractal surfaces.
      In conclusion the biological principle of the decrease in specific exchange
      intensity with increase in animal mass is discussed.

PMID- 16593328
TI  - Leucinopine, a characteristic compound of some crown-gall tumors.
AB  - An unusual compound has been found in crowngall tumors induced by those
      Agrobacterium tumefaciens strains that utilize neither octopine nor nopaline. The
      compound has been isolated and shown by proton and carbon-13 NMR spectroscopy and
      by synthesis to be N(2)-(1,3-dicarboxypropyl)-L-leucine, which also exists in a
      cyclized (i.e., lactam) form. This compound, which we name "leucinopine," was not
      detected in octopine tumors, nopaline tumors, or the tumors induced by A.
      tumefaciens strains 181 and EU6.

PMID- 16593329
TI  - Resonance of an unshared electron pair between two atoms connected by a single
      bond.
AB  - The reported structure of the dimer of a compound of bicovalent tin indicates
      that the tin-tin bond is of a new type. It can be described as involving
      resonance between two structures in which there is transfer of an electron pair
      from one tin atom to the other. The tin atoms are connected by a single covalent
      bond (each also forms two covalent bonds with carbon atoms), and an unshared
      electron pair resonates between the fourth sp(3) orbitals of the two atoms.
      Similar structures probably occur in digermene and distannene.

PMID- 16593330
TI  - Nitrogen photoreduction on desert sands under sterile conditions.
AB  - Sands from various geographic locations reduce N(2) from the air to NH(3) and
      traces of N(2)H(4) on exposure to sunlight. This N(2) photofixation occurs under
      sterile conditions on the surface of finely dispersed titanium minerals such as
      rutile, utilizing reducing equivalents generated through the photolysis of
      chemisorbed H(2)O. Abiological N(2) photofixation is suggested to be part of the
      nitrogen cycle in arid and semiarid regions. It is estimated that about 10 x
      10(5) tons of N(2) is photoreduced on the total surface of the earth's deserts
      per year.

PMID- 16593331
TI  - On an operator arising in the Calderon-Zygmund method of rotations and the
      Bramble-Hilbert lemma.
AB  - In this article sharp estimates are obtained for an operator that is a quadratic
      average with respect to v of one-dimensional Hardy-Littlewood maximal functions
      in the directions v. This operator arises naturally in Fourier analysis and
      numerical analysis.

PMID- 16593332
TI  - Photosynthetic electron transport from water to NADP driven by photosystem II in
      inside-out chloroplast vesicles.
AB  - It is now widely held that the light-induced noncyclic (linear) electron
      transport from water to NADP(+) requires the collaboration in series of the two
      photosystems that operate in oxygen-evolving cells: photosystem II (PSII)
      photooxidizes water and transfers electrons to photosystem I (PSI); PSI
      photoreduces ferredoxin, which in turn reduces NADP(+) (the Z scheme). However, a
      recently described alternative scheme envisions that PSII drives the noncyclic
      electron transport from water to ferredoxin and NADP(+) without the collaboration
      of PSI, whose role is limited to cyclic electron transport [Arnon, D. I.,
      Tsujimoto, H. Y. & Tang, G. M.-S. (1981) Proc. Natl. Acad. Sci. USA 78, 2942
      2946]. Reported here are findings at variance with the Z scheme and consistent
      with the alternative scheme. Thylakoid membrane vesicles were isolated from
      spinach chloroplasts by the two-phase aqueous polymer partition method. Vesicles,
      originating mainly from appressed chloroplast membranes that are greatly enriched
      in PSII, were turned inside-out with respect to the original sidedness of the
      membrane. With added plastocyanin, ferredoxin, and ferredoxin-NADP(+) reductase,
      the inside-out vesicles enriched in PSII gave a significant photoreduction of
      NADP(+) with water as electron donor, under experimental conditions that appear
      to exclude the participation of PSI.

PMID- 16593333
TI  - Molecular cloning and sequence analysis of the cyanobacterial gene for the large
      subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase consists of large subunits (LS)
      and small subunits. In plants, the LS is encoded in chloroplast DNA and the small
      subunit, in nuclear DNA. In cyanobacteria, both subunits are thought to be
      encoded in chromosomal DNA because of prokaryotes. The gene for the LS of
      ribulose-1,5-bisphosphate carboxylase/oxygenase from a cyanobacterium, Anacystis
      nidulans 6301, has been cloned in pBR322 and subjected to sequence analysis. The
      coding region contains 1,416 base pairs (472 codons). The deduced amino acid
      sequence of A. nidulans LS protein shows 80% homology with sequences of maize,
      spinach, and tobacco LS proteins; the nucleotide sequence of A. nidulans LS gene
      shows 70% homology with sequences of the plant genes. Between A. nidulans LS and
      the plant LS proteins there is exact sequence homology around the lysine residue
      to which the activator CO(2) binds and around the two lysine residues to which
      ribulose 1,5-bisphosphate binds. The amino acid sequence where the LS binds to
      the small subunit is also highly conserved. From comparison of the LS proteins of
      A. nidulans and the three plants, the rate of amino acid substitution is
      estimated to be 0.25-0.5 x 10(-9) per year per site, which is far below the
      median value of various types of proteins (1.2 x 10(-9) for hemoglobin alpha).
      The LS protein is thus a conserved protein.

PMID- 16593334
TI  - Nucleotide sequence of the S-2 mitochondrial DNA from the S cytoplasm of maize.
AB  - Mitochondria from the S male-sterile cytoplasm (cms-S) of maize contain two
      plasmid-like DNAs, S-1 and S-2, that appear to be prominently involved with the
      cytoplasmic male sterility trait. The complete nucleotide sequence of the S-2 DNA
      molecule was determined by the chain termination method. The linear S-2 DNA
      molecule contains 5,452 base pairs and is terminated by exact 208-base-pair
      inverted repetitions. Two large open reading frames were identified in the S-2
      DNA, suggesting the possibility of protein-encoding genes. The nucleotide
      sequence of the S-2 termini are discussed with regard to models proposed for the
      replication of linear DNA molecules.

PMID- 16593335
TI  - Stimulation of blowfly feeding behavior by octopaminergic drugs.
AB  - Adult blowflies (Phormia regina Meigen) injected with the octopaminergic drug
      demethylchlordimeform (10 mug per fly) exhibited enhanced proboscis extension
      responses when their tarsae were touched to water or aqueous sucrose. They drank
      more water than saline-injected control flies did but the quantity imbibed was
      within the normal fluid intake capacity. They became grossly hyperphagic when
      offered 1 M sucrose, doubling (and in some cases even tripling) their initial
      body weights. Three other drugs enhanced tarsal responsiveness and induced
      hyperphagia: DL-octopamine, clonidine (which is known to stimulate octopaminergic
      receptors in insects), and pargyline, a monoamine oxidase inhibitor. Yohimbine,
      an antagonist of one class of octopaminergic receptor in insects, prevented the
      hyperphagia induced by all four drugs. Dopamine, 5-hydroxytryptamine, and DL
      norepinephrine failed to cause hyperphagia. These results suggest that
      octopaminergic receptors in the nervous system of the blowfly positively modulate
      feeding and drinking behavior.

PMID- 16593336
TI  - Molecular area effects in Cepaea.
AB  - Enzyme polymorphisms in the land snail Cepaea nemoralis in the central Pyrenees
      show concordant geographic patterns of strong differentiation that are not
      correlated with the distributions of characters of shell color and banding or
      with the major pattern of variation in climate and vegetation type. Three regions
      of relative genetic uniformity separated by steep clines in allele frequencies
      are designated as "molecular area effects." A model of allopatric differentiation
      of populations in temporary geographic isolation during the last period of
      Pleistocene glaciation, followed by invasion of the Pyrenees and hybridization in
      secondary contact, is proposed to account for the present-day pattern of genetic
      differentiation. The genetic structure of the Pyrenean populations of C.
      nemoralis is not interpretable in terms of stasipatric or parapatric models of
      speciation.

PMID- 16593337
TI  - Nucleolar dominance in polytene cells of Drosophila.
AB  - Previous studies indicate that genes from only one of the cell's nucleolus
      organizers undergo multiple rounds of DNA replication in polytene cells of
      Drosophila. This report presents evidence that this effect is mediated by a
      function that is associated with the ribosomal genes of the dominant or
      replicating X chromosome. This function can act in trans to result in replication
      of the ribosomal genes on the recessive X chromosome in flies that are bobbed for
      the dominant X chromosome. In these cases, ribosomal genes from both chromosomes
      undergo polytenization. Heterochromatic regions that flank the nucleolus
      organizer have little or no effect on nucleolar dominance. In addition, deletion
      of the compensatory response (cr(+)) locus does not affect the dominance,
      suggesting that ribosomal gene compensation and nucleolar dominance in polytene
      cells of Drosophila are separate genetic phenomena.

PMID- 16593338
TI  - Drosophila locus with gene-dosage effects on rhodopsin.
AB  - Mutations that decrease the amplitude of the prolonged depolarizing
      afterpotential (PDA) in Drosophila melanogaster have been shown to have reduced
      rhodopsin content in the rhabdomeres of photoreceptor cells. In the present
      study, a genetic analysis of a class of third chromosome PDA-defective mutants
      localized the ninaE locus to the salivary band region 92A-B. In flies with only
      one copy of this region instead of the normal two copies, and in ninaE
      heterozygotes, the rhodopsin content of the major class of photoreceptors is
      reduced. Three doses of this region increase the rhodopsin content of these
      photoreceptors. These characteristics of the ninaE locus are expected of the
      structural gene encoding the major species of opsin in the Drosophila compound
      eye.

PMID- 16593339
TI  - Cell-type-specific gene expression and acatalasemic peroxisomes in a null Cat2
      catalase mutant of maize.
AB  - Cell separation studies in conjunction with immunocytochemical studies indicate
      that mesophyll cells and bundle-sheath cells, the dimorphic photosynthetic cell
      types in the leaves of the C(4) plant Zea mays, differ in their catalase
      composition. In particular, catalase-2, the product of the Cat2 gene, is found
      primarily in the bundle-sheath cells, whereas catalase-3, the product of the Cat3
      gene, is found primarily in the mesophyll cells. Electron microscopic
      observations reveal that bundle-sheath cells of A16, a mutant line lacking
      expression of the Cat2 gene in all tissues examined, contain numerous
      peroxisomes, but they are acatalasemic as determined by staining with 3,3'
      diaminobenzidine. The significance of this mutant in physiological studies is
      discussed.

PMID- 16593340
TI  - Recognition of female kin by male bees through olfactory signals.
AB  - After males of Lasioglossum zephyrum (Hymenoptera: Halictidae) have first been
      exposed to a conspecific female, the attractiveness of a second female diminishes
      with increasing genealogical relationship between the two females. The most
      parsimonious explanation for this is a polygenically controlled female sex
      pheromone. Nonrandom mating preferences may markedly affect gene flow within and
      between natural populations. Polygenically controlled sex pheromones probably
      also enhance kin recognition among females and, thus, influence the evolution of
      eusocial behavior in bees and wasps.

PMID- 16593341
TI  - International productivity comparisons (A Review).

PMID- 16593342
TI  - Dielectric constant of water at very high temperature and pressure.
AB  - Pertinent statistical mechanical theory is combined with the available
      measurements of the dielectric constant of water at high temperature and pressure
      to predict that property at still higher temperature. The dielectric constant is
      needed in connection with studies of electrolytes such as NaCl/H(2)O at very high
      temperature.

PMID- 16593343
TI  - van't Hoff-van der Waals osmotic pressure and energy transformers.
AB  - We find the van't Hoff relations between osmotic pressure, freezing point
      depression, and boiling point elevation provide a clue on how, by using salt
      solutions, one may lower the cost of extracting power from low-grade heat
      sources. In particular, the ratio of 7 between the heat of evaporation and the
      heat of freezing of pure water suggests a chemical system that raises 7-fold the
      temperature difference between heat source and heat sink, while decreasing by the
      same factor the heat flux. Heat exchangers dominate the cost of heat engines
      operating upon low-grade heat. Their area for a fixed power output is inversely
      proportional to the available temperature differential. Herein lies the potential
      for a great cost reduction. We show that the simple van der Waals concept of a
      gas of hard elastic spheres suffices to understand the colligative properties of
      salt solutions, at least up to the concentration of the eutectic composition.
      This concept enables us to physically interpret the thermodynamic processes
      during the concentration of salt solutions by evaporation and during the mixing
      of ice and solid salt hydrates at their eutectic temperature. These are identical
      to the thermodynamic processes taking place during the isothermal compression and
      expansion of gases in pumps and in turbines.

PMID- 16593344
TI  - Free jet excitation and emission spectra of diphenylbutadiene.
AB  - Highly resolved emission and one-photon fluorescence excitation spectra for 1,4
      diphenyl-1,3-butadiene seeded in a supersonic expansion of helium have been
      measured. The spectra show a long-lived (52.8 nsec for excitation at the 0-0)
      state at 29,652.5 cm(-1), approximately 1,150 cm(-1) below the well-characterized
      (1)B(u) state, which is assigned as (1)A(g)-i.e., we have directly observed a
      polyene (1)A(g) state in the gas phase. Emission spectra and decay times for the
      (1)A(g) state were measured at a number of different excitation energies. These
      data clarify the ordering of excited singlet states and the photophysical
      behavior of diphenylbutadiene.

PMID- 16593345
TI  - The second law as a selection principle: The microscopic theory of dissipative
      processes in quantum systems.
AB  - The second law of thermodynamics, for quantum systems, is formulated, on the
      microscopic level. As for classical systems, such a formulation is only possible
      when specific conditions are satisfied (continuous spectrum, nonvanishing of the
      collision operator, etc.). The unitary dynamical group can then be mapped into
      two contractive semigroups, reaching equilibrium either for t --> +infinity or
      for t --> -infinity. The second law appears as a symmetry-breaking selection
      principle, limiting the observables and density functions to the class that tends
      to thermodynamic equilibrium in the future (for t --> +infinity). The physical
      content of the dynamical structure is now displayed in terms of the appropriate
      semigroup, which is realized through a nonunitary transformation. The
      superposition principle of quantum mechanics has to be reconsidered as
      irreversible processes transform pure states into mixtures and unitary
      transformations are limited by the requirement that entropy remains invariant. In
      the semigroup representation, interacting fields lead to units that behave
      incoherently at equilibrium. Inversely, nonequilibrium constraints introduce
      correlations between these units.

PMID- 16593346
TI  - Self-adjointness of the Fourier expansion of quantized interaction field
      Lagrangians.
AB  - Regularity properties significantly stronger than were previously known are
      developed for four-dimensional non-linear conformally invariant quantized fields.
      The Fourier coefficients of the interaction Lagrangian in the interaction
      representation-i.e., evaluated after substitution of the associated quantized
      free field-is a densely defined operator on the associated free field Hilbert
      space K. These Fourier coefficients are with respect to a natural basis in the
      universal cosmos M, to which such fields canonically and maximally extend from
      Minkowski space-time M(0), which is covariantly a submanifold of M. However,
      conformally invariant free fields over M(0) and M are canonically identifiable.
      The kth Fourier coefficient of the interaction Lagrangian has domain inclusive of
      all vectors in K to which arbitrary powers of the free hamiltonian in M are
      applicable. Its adjoint in the rigorous Hilbert space sense is a(-k) in the case
      of a hermitian Lagrangian. In particular (k = 0) the leading term in the
      perturbative expansion of the S-matrix for a conformally invariant quantized
      field in M(0) is a self-adjoint operator. Thus, e.g., if varphi(x) denotes the
      free massless neutral scalar field in M(0), then integralM(0):varphi(x)(4):d(4)x
      is a self-adjoint operator. No coupling constant renormalization is involved
      here.

PMID- 16593347
TI  - Sequence of the nifD gene coding for the alpha subunit of dinitrogenase from the
      cyanobacterium Anabaena.
AB  - The nucleotide sequence of nifD, the structural gene for the alpha subunit of
      dinitrogenase from Anabaena 7120, has been determined. The coding sequence
      contains 1,440 nucleotides, which predict an amino acid sequence of 480 residues
      and M(r) of 54,283. The predicted sequence contains eight cysteines, of which
      five are conserved with respect to adjoining sequences and position relative to
      the alpha subunits of dinitrogenase from Azotobacter, Clostridium, and
      Klebsiella. Because there are also five conserved cysteines in the beta subunit
      of Anabaena dinitrogenase [Mazur, B. J. & Chiu, C.-F. (1982) Proc. Natl. Acad.
      Sci. USA 79, 6782-6786], the number of cysteine residues participating as ligands
      to FeS clusters is likely to be 20 per alpha(2)beta(2) tetramer. This number is
      sufficient to accommodate the known four Fe(4)S(4) clusters, leaving at least
      four cysteines to be shared among the two FeMo cofactors and the more poorly
      characterized two-iron center. Although the alpha- and beta-subunit gene
      sequences are not recognizably homologous, their secondary structures, predicted
      from the sequences, indicate similar domains around three of the conserved
      cysteine residues.

PMID- 16593348
TI  - Intrinsic resistance to the lethal effects of x-irradiation in insect and
      arachnid cells.
AB  - Twelve cell lines representing 10 genera of three orders (Diptera, Lepidoptera,
      and Orthoptera) of the class Insecta and one cell line (Acarina) from the class
      Arachnida were examined to discern their sensitivity to the lethal effects of x
      irradiation. Radiosensitivity was measured by a combination of colony formation
      and population growth curve techniques. Each of these arthropod cell lines is
      significantly more radioresistant than mammalian cells, though the degree of
      resistance varies greatly with order. Dipteran cells are 3 to 9 times and
      lepidopteran cells 52 to 104 times more radioresistant than mammalian cells.
      Orthopteran and acarine cells are intermediate in radiosensitivity between
      dipteran and lepidopteran cells. These cells, especially the lepidopteran, should
      be valuable in determining the molecular nature of repair mechanisms that result
      in resistance to ionizing radiation.

PMID- 16593349
TI  - Stimulus-response coupling in sponge cell aggregation: Evidence for calcium as an
      intracellular messenger.
AB  - Aggregation of dissociated sponge cells has been proposed as a model for cell
      cell recognition mediated by a specific proteoglycan aggregation factor
      (Microciona aggregation factor). To test whether sponge cells undergo stimulus
      response coupling in which intracellular Ca is a messenger, aggregation of
      mechanically dissociated cells was studied. Changes in light transmission through
      cell suspensions paralleled aggregation as judged by microscopy. In the presence,
      but not absence, of Ca (>5 mM) partially purified Microciona aggregation factor
      aggregated both living and glutaraldehyde-fixed cells. Evidence for a messenger
      role of Ca was the following: (i) Addition of Ca to Ca-depleted cells induced
      aggregation that varied with [Ca]. (ii) Addition of Ca ionophores (A23187 and
      ionomycin) caused aggregation that varied with [Ca] and far exceeded that
      provoked by Ca alone. Glutaraldehyde-fixed cells did not respond to ionophores
      with or without Ca. (iii) Calcium antagonists inhibited aggregation. These
      included inhibitors of the Ca-calmodulin complex (N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide hydrochloride and 1-[bis(p-chlorophenyl)methyl]-3-[2,4
      dichloro-beta-(2,4-dichlorobenzyloxyl)phenylethyl]imidazolinium chloride), Ca
      channel blockers (La, Co, Cd, and verapamil), and three nonsteroidal anti
      inflammatory agents (indomethacin, ibuprofen, and piroxicam). Results indicated
      not only that early events of sponge aggregation can be quantified by continuous
      recording but that aggregation is not simply due to passive agglutination of
      inert cells by an extracellular proteoglycan. Rather, sponge cells recognize
      surface ligands to which they respond by Ca-dependent stimulus-response coupling.

PMID- 16593350
TI  - Ornitholimnology: Effects of grazing by the Andean flamingo (Phoenicoparrus
      andinus).
AB  - Experimental exclusion of the Andean flamingo (Phoenicoparrus andinus) from
      shallow water areas of a salt lake in the Bolivian Andes caused large increases
      in the biomass of microorganisms inhabiting the surface sediments, especially a
      large diatom (Surirella wetzeli), amebas, ciliates, and nematodes. This is a
      conservative demonstration of the influences that water birds in general exert on
      the structure of aquatic ecosystems.

PMID- 16593351
TI  - Transmission of chloroplast genes in triploid and tetraploid zygospores of
      Chlamydomonas reinhardtii: Roles of mating-type gene dosage and gametic
      chloroplast DNA content.
AB  - Diploid clones homozygous (mt(+)/mt(+) or mt(-)/mt(-)) or heterozygous (mt(+)/mt(
      ); phenotypically mt(-)) for the mating-type locus and homoplasmic for a
      chloroplast marker conferring resistance to an antibiotic were isolated by
      artificially induced cell fusion or sexual mating. These diploids were crossed
      with haploid or diploid strains of opposite mating type and carrying another
      chloroplast marker. The transmission of the chloroplast genes was analyzed in the
      triploid and tetraploid zygospores in comparison with diploid zygospores used as
      controls. The transmission was almost exclusively maternal (mt(+)) (>94%) in the
      crosses mt(+) x mt(-), mt(+)/mt(+) x mt(-), and mt(+)/mt(+) x mt(-)/mt(-). The
      transmission was preferentially maternal (>76%) in the crosses mt(+) x mt(-)/mt(
      ) whereas in the crosses mt(+) x mt(+)/mt(-), <50% of the zygospores transmitted
      the chloroplast allele of maternal (mt(+)) origin. The zygospores produced in
      crosses mt(+)/mt(+) x mt(+)/mt(-) transmitted the alleles from both parents in
      >60% of cases. The results show that (i) the presence of one mt(+) allele in the
      mt(+)/mt(-) (phenotypically mt(-)) diploid gametes and (ii) the higher amount of
      chloroplast DNA molecules (input) present in the diploid gametes versus the
      haploid ones favor the transmission of the chloroplast allele contributed by
      these gametes. Moreover, because the zygospores issued from crosses mt(+)/mt(+) x
      mt(-) and mt(+) x mt(+)/mt(-) were genotypically identical mt(+)/mt(+)/mt(-)) but
      behaved very differently in their chloroplast gene transmission, it was concluded
      that the molecular events leading to preferential elimination of paternal DNA
      copies must occur before the fusion of nuclei or chloroplasts in the newly formed
      zygotes.

PMID- 16593352
TI  - Charged amino acids as spectroscopic determinants for chlorophyll in vivo.
AB  - In this paper we propose that the large spectroscopic red shifts observed for
      chlorophyll (Chl) and bacteriochlorophyll (BChl) in vivo may be due to charged
      amino acids in the binding site. Molecular orbital calculations of the transition
      energies of Chl in the field of external charges are carried out. The calculated
      wavelength shifts induced by these charges are comparable in magnitude to those
      observed in vivo. Moreover the size of the shifts increases in the order BChl b >
      BChl a > Chl a, which is the observed trend. The ability of the calculations to
      account for both the absolute and relative magnitudes of the wavelength shifts
      argues for the validity of the model. Further indirect support comes from the
      recent demonstration that charged amino acids are responsible for the colors of
      visual pigments and bacteriorhodopsin. In addition to their effects on spectra
      the presence of external charges induces large changes in the ionization
      potential of Chl molecules and thus might explain the in vivo alteration of the
      oxidation potentials in reaction centers.

PMID- 16593353
TI  - Specific cell-cell contact serves as the developmental signal to deactivate
      discoidin I gene expression in Dictyostelium discoideum.
AB  - Specific cell-cell contact is a major regulatory signal controlling cell
      differentiation in Dictyostelium discoideum, causing dramatic changes in the
      developmental program of gene expression. In this report, we focus on the
      relationships between specific cell-cell contact and the activity of the genes
      for discoidin I, an endogenous lectin that has been implicated in the cell-cell
      cohesion process. By performing quantitative RNA dot-hybridization assays and RNA
      gel blot-hybridization analyses, using as a probe a recombinant plasmid
      containing a discoidin I cDNA insert, we have measured changes in discoiding I
      mRNA levels during normal development and in response to specific manipulations
      of the state of cellular aggregation. Our major findings are as follows. (i)
      During normal development on filters, there is a close temporal correspondence
      between the establishment of specific cell-cell contacts and the decline in
      discoidin I mRNA levels. By the tight-aggregate stage, discoidin I mRNA is barely
      detectable. (ii) When tight aggregates are disaggregated and the cells are
      maintained in the disaggregated state, there is a dramatic rise in discoidin I
      mRNA content. (iii) When cells are developed in suspension (conditions that
      interfere with the establishment of tight cell-cell contacts), discoidin I mRNA
      accumulates to abnormally high levels, and these persist well after the levels in
      filter-developed cells have declined. Taken together, these results strongly
      suggest that cell-cell contact is the normal developmental signal to deactivate
      discoidin I gene expression; thus, a contact-deactivated gene for which a
      recombinant DNA probe is available has now been identified. Furthermore, we
      demonstrate that exogenous cAMP almost completely blocks the disaggregation
      induced reactivation of discoidin I gene expression. Possible mechanistic
      relationships between specific cell-cell contact, intracellular cAMP levels, and
      developmental gene expression are discussed.

PMID- 16593354
TI  - Unequal crossing-over associated with asymmetrical synapsis between nomadic
      elements in the Drosophila melanogaster genome.
AB  - The molecular structure of reciprocal duplications and deficiencies produced by
      unequal crossing-over at the white (w) locus of Drosophila melanogaster females
      heterozygous for the alleles w(a) and w(a4) has been examined. A transposable,
      copia-like element is found at the rearrangement breakpoints. Further
      characterization indicates that asymmetrical pairing between two copies of this
      element, which are at least 60 kilobases apart in the parental chromosomes,
      followed by a crossover within the paired elements, is responsible for the
      duplication and deficiencies observed. The frequency of these events is high
      compared with normal homologous exchange, implying that synaptic pairing during
      meiosis must be sufficiently flexible as to allow efficient recognition of
      sequences located in nonidentical positions on homologous chromosomes. These
      results suggest a possible mechanism for the generation of tandem duplications in
      eukaryotic organisms.

PMID- 16593355
TI  - Aphelion clustering of "new" comets: Star tracks through Oort's cloud.
AB  - An explanation is proposed for the observed and often discussed clustering of
      long-period comet aphelia on the sky. Poisson and several multinomial
      distributions are applied to the most conspicuous cluster, considering only the
      80 "new" and 59 "intermediate" comets with the best-determined orbits. The
      observed number of aphelion points in adjacent areas in two tests with 24 and 36
      equal sky areas, respectively, shows a large deviation from a random
      distribution. The expected probability frequency for this to happen by chance is
      <0.1% for the "new" comets alone; it is further reduced when "new" and
      "intermediate" comets are combined. When these comets are analyzed separately
      from others, it is found that the clustering is the result of perturbations of
      their original orbits by the passage of a star, or a stellar system, through
      Oort's cloud a few million years ago. Because the statistical effect on the
      change of a comet's angular momentum about the sun is proportional to the square
      of the ratio of the mass to the velocity of a star relative to the sun, it is a
      priori probable that passages by a few stars should produce clustering of the
      aphelia, as is discussed in detail.

PMID- 16593356
TI  - A conjugate decomposition of the Euclidean space.
AB  - Given a closed convex cone K in the n-dimensional real Euclidean space R(n) and
      an nxn real matrix A that is positive definite on K, we show that each vector in
      R(n) can be decomposed into a component that lies in K and another that lies in
      the conjugate cone induced by A and such that the two vectors are conjugate to
      each other with respect to A + A(T). As a consequence of this decomposition we
      establish the following characterization of positive definite matrices: An nxn
      real matrix A is positive definite if and only if it is positive definite on some
      closed convex cone K in R(n) and (A + A(T))(-1) exists and is positive
      semidefinite on the polar cone K(0). If K is a subspace of R(n), then K(0) is its
      orthogonal complement K[unk]. Other applications include local duality results
      for nonlinear programs and other characterizations of positive definite and
      semidefinite matrices.

PMID- 16593357
TI  - Rational approximations to solutions of linear differential equations.
AB  - Rational approximations of Pade and Pade type to solutions of differential
      equations are considered. One of the main results is a theorem stating that a
      simultaneous approximation to arbitrary solutions of linear differential
      equations over C(x) cannot be "better" than trivial ones implied by the Dirichlet
      box principle. This constitutes, in particular, the solution in the linear case
      of Kolchin's problem that the "Roth's theorem" holds for arbitrary solutions of
      algebraic differential equations. Complete effective proofs for several
      valuations are presented based on the Wronskian methods and graded subrings of
      Picard-Vessiot extensions.

PMID- 16593358
TI  - Chloroperoxidase generation of singlet Delta molecular oxygen observed directly
      by spectroscopy in the 1- to 1.6-mum region.
AB  - The (0,0) (1)Delta(g) --> (3)Sigma(-) (g) singlet molecular oxygen
      chemiluminescence emission from a biological reaction system, chloroperoxidase
      (EC 1.11.1.10) acting on hydrogen peroxide at low pH (phosphate buffer, pH 2.85)
      with Cl(-) as a cosubstrate, was recorded with an ultrasensitive IR spectrometer.
      The strong chemiluminescence emission peak observed at 1.30 mum provides clear
      evidence of the enzymatic generation of (excited) singlet oxygen from peroxide in
      this system.

PMID- 16593359
TI  - Methanophosphagen: Unique cyclic pyrophosphate isolated from Methanobacterium
      thermoautotrophicum.
AB  - A unique cyclic pyrophosphate compound has been detected at 10-12 mM
      intracellular concentration in Methanobacterium thermoautotrophicum by in
      vivo(31)P NMR. This compound has been extracted from cells and purified by anion
      exchange chromatography. Studies with (1)H, (13)C, and (31)P NMR and fast-atom
      bombardment mass spectrometry have identified it as 2,3
      cyclopyrophosphoglycerate, an intramolecularly cyclized pyrophosphate of 2,3
      diphosphoglycerate. Chemical degradation to 2,3-diphosphoglycerate and synthesis
      by dicyclohexylcarbodiimide coupling of 2,3-diphosphoglycerate are consistent
      with this identification. It is suggested that this compound serves as a primary
      phosphagen in methanogens.

PMID- 16593360
TI  - Activation of plant quinate:NAD 3-oxidoreductase by Ca and calmodulin.
AB  - Quinate:NAD(+) 3-oxidoreductase (EC 1.1.1.24) from carrot cell suspension
      cultures has previously been shown to be activated by phosphorylation and
      inactivated by dephosphorylation. Here it is shown that the reactivation of the
      inactivated quinate:NAD(+) oxidoreductase is an enzyme-mediated process that
      requires ATP and protein kinase activity. The reactivation is completely
      inhibited by EGTA and can be restored by the addition of Ca(2+). Cyclic AMP at
      concentrations up to 5 muM did not have any effect on the reactivation either
      with or without EGTA in the medium. Calmodulin-depleted fractions containing
      quinate:NAD(+) oxidoreductase were obtained by passage of the crude extracts
      through an affinity column of 2-chloro-10-(3-aminopropyl)phenothiazine coupled to
      Sepharose 4B. The enzyme in this calmodulin-deficient fraction could be
      inactivated but not reactivated even in the presence of ATP and Ca(2+). However,
      addition of bovine brain calmodulin completely restored the activity of the
      enzyme. Half-maximal activation occurred at 130 nM calmodulin. We conclude from
      these data that the quinate:NAD(+) oxidoreductase is activated by a Ca(2+) - and
      calmodulin-dependent plant protein kinase.

PMID- 16593361
TI  - Prestalk and prespore differentiation in Dictyostelium as detected by cell type
      specific monoclonal antibodies.
AB  - Monoclonal antibodies specifically reactive against prestalk and prespore cells
      of the cellular slime mold Dictyostelium discoideum were obtained. By the use of
      these antibodies, we examined processes of differentiation of the two cell types
      during development. Cells stained with prespore-specific antibodies first
      appeared after 12-14 hr of starvation within cell aggregates with tips,
      coincidentally with the appearance of other prespore markers. The number of
      prespore cells then increased to a level of 70-80% of total cells at the slug
      stage. By contrast, cells stained with prestalk-specific antibodies began to
      appear after 3 hr of starvation and thereafter increased in number to a maximum
      of ca. 80% after 12 hr of starvation. Stained cells appeared at random in the
      aggregation field and were not morphologically distinguishable from unstained
      cells. Furthermore, cells showed a considerable heterogeneity in the amount of
      antigen they contain. Concomitantly with the increase in prespore cells, the
      number of cells stained by the prestalk antibodies decreased to a level of ca.
      20% by the slug stage. From these experiments, we suggest that the prestalk
      antigen is synthesized in the majority of cells during the early period of
      aggregation. Within tight cell aggregates, some of these cells lose the antigen
      to become prespore cells and the normal proportion between the two cell types
      will eventually result within slugs.

PMID- 16593362
TI  - Variation at the 87A heat shock locus in Drosophila melanogaster.
AB  - Restriction maps for 25 kilobases of DNA around the 87A7 heat shock locus have
      been determined in 29 chromosomes isolated from a natural population. The
      heterozygosity per nucleotide and the proportion of polymorphic nucleotide sites
      were estimated to be 0.0024 and 0.007, respectively. The mean number of
      insertional differences in this region between random pairs of chromosomes was
      0.95. A significant amount of this variation was due to the insertion of large
      transposable elements. All the insertion/deletion events were found in a region
      less than 2 kilobases in size. This could either be due to nonrandom integration
      or to differences in the intensity of selection against DNA insertion at
      different sites.

PMID- 16593363
TI  - Mutations affect storage and use of memory differentially in Drosophila.
AB  - The behavior of normal Drosophila and of X-linked olfactory conditioning mutants
      was analyzed by using an olfactory memory choice task. Memory in normal flies was
      optimal at 5-12 min after training and then decayed slowly. Memory in the mutants
      was 40-80% of normal when tested 30 sec after training but it decayed rapidly and
      was very low after 7 min. Successive conditioning experiments indicated that some
      types of mutants can behave as though they store information for a longer period
      than that revealed by straightforward memory tests, but this information reveals
      itself only by interaction with newly acquired information in a conflict
      situation. It thus seems that the mutations can either prevent the formation of
      normal memory or prevent memory from evoking a normal behavioral response.

PMID- 16593364
TI  - Asparaginylglucose: Novel type of carbohydrate linkage.
AB  - The Halobacterial cell wall glycoprotein was recently shown to contain two types
      of sulfated saccharides: a repetitive saccharide and a nonrepetitive saccharide
      composed of glucuronic acid and glucose. A new type of N-glycosidic linkage is
      found in this latter type of saccharide: glucose is N-glycosidically linked to
      the polypeptide chain through the amido nitrogen of an asparagine residue, as
      shown by chemical analyses, proton magnetic resonance spectroscopy, and mass
      spectroscopy of an isolated asparaginyl saccharide. The only N-glycosidic linkage
      known so far is between the amido nitrogen of asparagine and N-acetylglucosamine.

PMID- 16593365
TI  - Primary structure of streptococcal Pep M5 protein: Absence of extensive sequence
      repeats.
AB  - Extensive sequence repeats have been observed in a biologically active fragment
      of type 24 streptococcal M protein, namely Pep M24 [Beachey, E. H., Sayer, J. M.
      & Kang, A. H. (1978) Proc. Natl. Acad. Sci. USA 75, 3163-3167]. To determine
      whether such extensive repetition in sequence is a common characteristic of the
      antiphagocytic streptococcal M proteins, we have determined the sequences of the
      clostripain peptides of Pep M5, a biologically active fragment of the type 5 M
      protein that is analogous to Pep M24. These sequences, together with the amino
      terminal sequence of the whole molecule, accounted for nearly two thirds of the
      Pep M5 molecule. However, extensive identical repeats of the kind observed in Pep
      M24 were not present in Pep M5. Preliminary study of the amino acid sequence
      analysis of the M protein from type 6 Streptococcus has also indicated the
      absence of sequence repeats within the regions of this molecule examined so far.
      These results suggest that extensive sequence repeats may not be a common
      characteristic of M-protein molecules. On the other hand, the seven-residue
      periodicity of the nonpolar residues, a characteristic of alpha-helical coiled
      coil structures, appeared to extend over most of the Pep M5 molecule. This
      feature has been observed previously for the partial sequences of three M protein
      serotypes. Thus, the important element of the M-protein structure appears to be
      the seven-residue periodicity necessary for the maintenance of the coiled-coil
      structure rather than extensive identical amino acid sequence repeats.

PMID- 16593366
TI  - Isolation of the nitrogen assimilation regulator NR(I), the product of the glnG
      gene of Escherichia coli.
AB  - The product of the glnG gene, a member of the complex glnALG operon, is an
      essential component in the response of Escherichia coli K-12 and other enteric
      bacteria to nitrogen-limited growth. We have purified this protein which we
      propose to call "NR(I)," for nitrogen regulator I, to about 95% purity from an
      overproducing strain. Purified NR(I) was identified as a dimer by gel filtration.
      NR(I) specifically inhibited initiation of transcription from a DNA fragment
      containing the glnL promoter but was without effect on lacZ transcription. We
      determined the intracellular concentration of NR(I) under different growth
      conditions by using immunological techniques. The ratio of glutamine synthetase
      polypeptides, the product of the glnA gene, to NR(I) polypeptides was about 80:1.
      NR(I) was not rapidly degraded after ammonia shock, even though the ability to
      activate nitrogen-controlled systems was lost.

PMID- 16593367
TI  - Normal mode paths for hydrogen exchange in the peptide ferrichrome.
AB  - Possible paths for exposure to solvent and hydrogen exchange of the amide protons
      of ferrichrome, a cyclic hexapeptide, are examined. The paths are obtained from
      calculations of the vibrational normal modes of ferrichrome and correspond to low
      energy atomic displacements away from the local minimum in the multidimensional
      conformational space of the molecule. Exposure of exchangeable groups along the
      normal modes was determined by using the solvent accessible surface area
      algorithm of Lee and Richards. Three of the exchangeable protons (Gly(1,2,3,))
      are largely exposed to solvent in the x-ray structure while the remaining three
      exchangeable protons of the ornithines are totally shielded from solvent. A very
      small number of normal mode displacements are found to expose the Orn(2) and
      Orn(3) amide groups while the Orn(1) amide proton remains shielded from solvent
      for all the paths studied. The effective paths for exposure of Orn(2) and Orn(3)
      correspond to the lowest frequency ( approximately 18 cm(-1)) motions. The paths
      are characterized in terms of the magnitude and energy of atomic displacements,
      correlated changes in dihedral angles, and the resulting changes in exposure and
      hydrogen bonding of exchangeable groups.

PMID- 16593368
TI  - Dephosphorylation of a major sperm membrane protein is induced by egg jelly
      during sea urchin fertilization.
AB  - A 160-kilodalton (kDa) protein of Arbacia punctulata sperm is constitutively
      phosphorylated on serine residues, as shown by in vivo(32)PO(4) (3-) labeling.
      Exposure of sperm to solubilized egg jelly results in the immediate
      dephosphorylation (within 5 sec) of this protein and a simultaneous increase in
      its electrophoretic mobility (to an apparent molecular mass of 150 kDa). In its
      dephosphorylated form (150 kDa), the protein is a major component of the
      flagellar plasma membrane. In fact, silver-stained polyacrylamide gels show the
      160/150-kDa protein to be the third most abundant protein in the whole flagellum.
      The spermatozoan must pass through the egg jelly layer on its way to the egg
      surface. The jelly-induced dephosphorylation of such an abundant sperm membrane
      protein may be an important event in the successful interaction of sperm and egg
      during fertilization.

PMID- 16593369
TI  - Cell growth on liquid interfaces: Role of surface active compounds.
AB  - Anchorage-dependent fibroblasts can be cultured by using as a substrate the
      protein layer that spontaneously forms at the liquid-liquid interface between
      fluorocarbon fluids and tissue culture medium. For this novel substrate to be
      effective in supporting confluent cell layers, the protein monolayer must support
      the stresses exerted by spreading fibroblasts. The composition of the
      fluorocarbon fluid has a significant effect on the strength of the protein layer
      and, thus, on the patterns of cell growth. Evidence is presented demonstrating
      that a protein film, sufficiently strong to support cell growth, does not occur
      on purified fluorocarbon fluids but requires the presence of trace amounts of
      polar, surface active compounds. By the addition of small quantities of
      pentafluorobenzoyl chloride to alumina-treated fluorocarbon fluids, excellent
      interfacial substrates can be produced. We have applied this understanding to
      produce a liquid microcarrier system capable of general use with a variety of
      cells, including human fibroblasts. A microcarrier in which the fluorocarbon is
      replaced with polydimethyldiphenyl siloxane is also described.

PMID- 16593370
TI  - Thermotaxis of Dictyostelium discoideum amoebae and its possible role in
      pseudoplasmodial thermotaxis.
AB  - Thermotaxis by individual amoebae of Dictyostelium discoideum on a temperature
      gradient is described. These amoebae show positive thermotaxis at temperatures
      between 14 degrees C and 28 degrees C shortly (3 hr) after food depletion.
      Increasing time on the gradient reduces the positive thermotactic response at the
      lower temperature gradients (midpoint temperatures of 14, 16, and 18 degrees C),
      and amoebae show an apparent negative thermotactic response after 12 hr on the
      gradient. The thermotaxis response curve for "wild-type" amoebae after 16 hr on
      the gradient is similar to that shown for the pseudoplasmodia. Growth of the
      amoebae at a different temperature causes a shift in the thermotaxis response
      curve for the amoebae. This adaptation is similar to that shown for the
      pseudoplasmodia. Two mutants in thermotaxis, HO428 and HO813, show changes in
      amoebal thermotaxis similar to the observed changes in pseudoplasmodial
      thermotaxis. On the basis of the similarities between these responses,
      thermotaxis by the amoebae is proposed to be the basis for thermotaxis by the
      multicellular pseudoplasmodium.

PMID- 16593371
TI  - Isolation and characterization of the RAD3 gene of Saccharomyces cerevisiae and
      inviability of rad3 deletion mutants.
AB  - The RAD3 gene of Saccharomyces cerevisiae is required for nicking of DNA
      containing pyrimidine dimers or interstrand crosslinks. We have cloned the RAD3
      gene and physically mapped it to 2.6 kilobase of DNA. A DNA segment of the cloned
      RAD3 insert was ligated into plasmid YIp5, which transforms yeast by homologous
      integration, and shown to integrate at the RAD3 site in chromosome V, thus
      verifying the cloned DNA segment to be the RAD3 gene and not a suppressor. The
      RAD3 gene encodes a 2.5-kilobase mRNA, extending between the Kpn I site and the
      Sau3A1/BamHI fusion junction in plasmid pSP10, and the direction of transcription
      has been determined. The 2.5-kilobase transcript could encode a protein of about
      90,000 daltons. We also show the deletions of the RAD3 gene to be recessive
      lethals, indicating that the RAD3 gene plays an important role in other cellular
      processes in addition to incision of damaged DNA.

PMID- 16593372
TI  - Primary structure and neuronal effects of alpha-bag cell peptide, a second
      candidate neurotransmitter encoded by a single gene in bag cell neurons of
      Aplysia.
AB  - A discharge of impulse activity in a group of neuroendocrine cells, the bag
      cells, produces several types of prolonged responses in various identified
      neurons of the abdominal ganglion of Aplysia. Two excitatory responses are almost
      certainly mediated by egg-laying hormone, but this peptide cannot account for
      other responses, such as inhibition of left upper quadrant neurons. We report
      here the isolation from bag cell clusters of three structurally similar peptides,
      seven, eight, and nine residues long, that are candidate transmitters for
      mediating bag cell-induced inhibition. They may also serve as autoexcitatory
      transmitters since the seven-residue peptide produces a slow depolarization of
      the bag cells similar to that which occurs during bag cell discharge. The amino
      acid sequence of the largest peptide, termed alpha-bag cell peptide[1-9], is H
      Ala-Pro-Arg-Leu-Arg-Phe-Tyr-Ser-Leu-OH. The other two peptides are identical to
      alpha-BCP[1-9] except that they lack the COOH-terminal Ser-Leu or leucine
      residues. The three peptides inhibit left upper quadrant neurons at relative
      potencies of 10:30:1 (seven-, eight-, and nine-residue peptides, respectively).
      Recent molecular genetic analysis shows that both alpha-BCP[1-9] and egg-laying
      hormone are encoded by the same bag cell-specific gene. The multiple neuronal
      effects of bag cells are therefore likely to be mediated by at least two
      transmitters that are cleaved from a common precursor molecule.

PMID- 16593373
TI  - Reexamination of diversifying selection of polymorphic allozyme genes by using
      population cages in Drosophila melanogaster.
AB  - Several investigators have reported increased heterozygosity for allozyme markers
      in laboratory experiments simulating a variable environment and have concluded
      that there is diversifying selection for allozyme variants. We found no change in
      heterozygosity in 28 large population cages where temperature, food, and light
      were each set at three levels, two constant and one variable, in a factorial
      design. Specifically, there was no change in heterozygosity when 0, 1, 2, or 3
      factors were variable. The discrepancy between our negative results and earlier
      positive ones is that our experiments were started from a large caged population
      of flies which had been maintained for 6 years-long enough to be very near to
      linkage equilibrium. We suggest that the earlier results may have been the result
      of linkage between neutral, or nearly neutral, allozyme markers and selected loci
      or in some cases, inversions.

PMID- 16593374
TI  - X-ray diffraction by phospholipid monolayers on single-crystal silicon
      substrates.
AB  - Monolayers of dipalmitoyl phosphatidylcholine have been transferred from an air
      water interface to single-crystal silicon wafers previously alkylated with
      octadecyltrichlorosilane. By using synchrotron radiation it has been found
      possible to observe diffraction by single-crystal regions of these monolayers
      with negligible background scattering from the solid substrate. In one series of
      experiments, diffraction signals at Bragg spacings of 0.4247 +/- 0.0002 nm and
      0.4253 +/- 0.0002 nm were observed. The supported phospholipid monolayer crystals
      show remarkably high in-plane order: the positional coherence length is at least
      500 nm and the orientational order is better than 0.01 degrees . Preliminary
      temperature scans were carried out. The data reveal the existence of a phase
      transition at about 65 degrees C.

PMID- 16593375
TI  - Viscous, resistive magnetohydrodynamic stability computed by spectral techniques.
AB  - Expansions in Chebyshev polynomials are used to study the linear stability of one
      dimensional magnetohydrodynamic quasiequilibria, in the presence of finite
      resistivity and viscosity. The method is modeled on the one used by Orszag in
      accurate computation of solutions of the Orr-Sommerfeld equation. Two Reynolds
      like numbers involving Alfven speeds, length scales, kinematic viscosity, and
      magnetic diffusivity govern the stability boundaries, which are determined by the
      geometric mean of the two Reynolds-like numbers. Marginal stability curves,
      growth rates versus Reynolds-like numbers, and growth rates versus parallel wave
      numbers are exhibited. A numerical result that appears general is that
      instability has been found to be associated with inflection points in the current
      profile, though no general analytical proof has emerged. It is possible that
      nonlinear subcritical three-dimensional instabilities may exist, similar to those
      in Poiseuille and Couette flow.

PMID- 16593376
TI  - Adaptive choice of mean or median in estimating the center of a symmetric
      distribution.
AB  - An adaptive choice of the sample mean x(n) or the sample median m(n) is proposed
      for estimating the center of a symmetric distribution. This choice becomes
      correct as n --> infinity, and in simulation results for finite n it is almost as
      good as the better of x(n) and m(n).

PMID- 16593377
TI  - Chlamydomonas agglutinin is a hydroxyproline-rich glycoprotein.
AB  - The mt(+) sexual agglutinin from Chlamydomonas reinhardi is shown to contain
      approximately 12% hydroxyproline, and two inhibitors of hydroxyproline formation,
      alpha,alpha'-dipyridyl and 3,4-dehydroproline, are shown to block the production
      of agglutinin activity in an in vivo bioassay system. These results indicate that
      the agglutinin glycoprotein may be related to a class of hydroxyproline-rich
      glycoproteins found in the extracellular matrix of higher plants, several of
      which have been shown to have lectin activity.

PMID- 16593378
TI  - Cyanobacterial photosystem I: Morphology and aggregation behavior.
AB  - A simple procedure is described for the preparation of cyanobacterial photosystem
      I particles with a full complement of antenna chlorophyll a from Triton X-100
      solubilized thylakoid membranes. In the presence of >/=0.1% Triton X-100,
      photosystem I particles from Synechococcus 6301 were largely monodisperse. These
      particles, when negatively stained, appeared to approximate prolate ellipsoids 18
      x 8 nm. A value of 4-5 x 10(-19) cm(3) was estimated for the volume of the stain
      exclusion envelopes of the particles. At low concentrations of Triton X-100,
      photosystem I particles formed linear aggregates or sheets one-layer thick. The
      manner of aggregation was strongly dependent on protein concentration. Shadowed
      preparations of the sheets indicated a thickness of 8.0-8.5 nm.

PMID- 16593379
TI  - Offspring sex ratio in red-winged blackbirds is dependent on maternal age.
AB  - In a marsh-breeding population of red-winged blackbirds, the sex ratio of
      offspring that survived to leave the nest varied with maternal age. Old mothers
      produced an excess of male fledglings, middle-aged mothers produced almost equal
      proportions of males and females, and young mothers produced nearly twice as many
      females as males. More males than females hatched from the eggs of old mothers,
      whereas among newly hatched progeny of middle-aged and young mothers the sex
      ratio did not differ from unity. The hatching rate of eggs of old mothers was
      unusually low, suggesting that the biased sex ratio of their hatchlings may have
      been caused by more frequent death of female embryos, although other
      possibilities can be imagined. Starvation of nestlings after hatching also
      affected the sex ratio among young that left the nest. When starvation occurred,
      it fell principally on young produced by the last and next-to-last eggs laid in
      the clutch. Because old mothers allocated relatively more energy to those eggs
      than to earlier-laid eggs, whereas young mothers apportioned energy equally to
      their eggs, few nestlings of old mothers but many nestlings of young mothers
      starved. Most nestlings that died were male. It followed that the male bias in
      sex ratio of progeny of old mothers did not change between hatching and
      nestleaving, but the ratio among progeny of young mothers shifted after hatching
      to a strong bias favoring females at nest-leaving.

PMID- 16593380
TI  - Chromophore structure of the physiologically active form (P(fr)) of phytochrome.
AB  - Chromopeptides were prepared by proteolytic digestion of phytochrome (far-red
      absorbing form, P(fr)) and of phycocyanin. The phycocyanobilin peptide, the
      chromophore of which is Z,Z,Z-configurated, was modified to the Z,Z,E isomeric
      chromophore. It has been demonstrated earlier that the P(fr) chromopeptide and
      the Z,Z,E-configurated phycocyanin chromopeptide behave similarly with regard to
      spectral and chromatographic properties and reactivity. We present evidence here,
      obtained by high-resolution (1)H NMR spectroscopy, that both the modified
      phycocyanobilin chromophore and the phytochrome chromophore obtained directly
      from P(fr) are 15E-configurated.

PMID- 16593381
TI  - Spectrally distinct cytochrome b-563 components in a chloroplast cytochrome b-f
      complex: Interaction with a hydroxyquinoline N-oxide.
AB  - The two heme equivalents of cytochrome b-563 in the photosynthetic cytochrome b-f
      complex can be distinguished by their rate of reduction with dithionite at 25
      degrees C and by their optical absorption spectra at 77 K. The cytochrome b
      component that is rapidly reduced after addition of dithionite or reduced
      ferredoxin possesses an alpha band that splits at 77 K into two peaks, at 557 and
      561 nm. Prolonged incubation with reductant reveals a second, approximately
      equimolar cytochrome b component that has at 77 K an unsplit alpha-band maximum
      at 561 nm. The designations cytochrome b-563(H) and cytochrome b-563(L),
      respectively, are proposed for the rapidly and more slowly reduced cytochrome b
      563 components. Potentiometric titration establishes a midpoint potential, E(m),
      of -30 mV (electron change n approximately 2) for cytochrome b-563(H) and -150 mV
      (n = 1) for cytochrome b-563(L) at pH 7.5. The reduction potential of these
      components is raised by 2-heptyl-4-hydroxyquinoline N-oxide, giving E(m) values
      of +57 and -34 mV, respectively, with each titration slope approximating n = 2.

PMID- 16593382
TI  - Rapid recovery of chloroplast mutations affecting ribulosebisphosphate
      carboxylase/oxygenase in Chlamydomonas reinhardtii.
AB  - Based on the unique ability of chloroplast genes to recombine in Chlamydomonas
      reinhardtii, a collection of acetate-requiring mutants was screened for
      recombination with a mutation affecting ribulose-1,5-bisphosphate
      carboxylase/oxygenase [Rbu-1,5-P(2) carboxylase/oxygenase; 3-phospho-D-glycerate
      carboxy-lyase (dimerizing), EC 4.1.1.39]. This chloroplast mutation, rcl-u-1-10
      6C, causes the absence of Rbu-1,5-P(2) carboxylase/oxygenase activities and
      alters the isoelectric point of the larger subunit. Several mutants that
      displayed little or no recombination with 10-6C were recovered, and two lacked
      carboxylase activity. These new chloroplast mutants lack both large and small Rbu
      1,5-P(2) carboxylase/oxygenase subunits. The approach demonstrated here permits
      the routine recovery of chloroplast mutations affecting this enzyme. Multiple
      mutations in the Rbu-1,5-P(2) carboxylase/oxygenase large-subunit gene can be
      used to investigate the function and regulation of this enzyme and the regulation
      of chloroplast genes in general.

PMID- 16593383
TI  - Diffusion model of intergroup selection, with special reference to evolution of
      an altruistic character.
AB  - Assume a diploid species consisting of an infinite number of competing demes,
      each having N(e) reproducing members and in which mating is at random. Then
      consider a locus at which a pair of alleles A and A' are segregating, where A' is
      the "altruistic allele," which has selective disadvantage s' relative to A with
      respect to individual selection, but which is beneficial for a deme in
      competition with other demes; namely, a deme having A' with frequency x has the
      advantage c(x - x) relative to the average deme, where c is a positive constant
      and x is the average of x over the species. Let varphi = varphi(x;t) be the
      distribution function of x among demes in the species at time t. Then, we have
      partial differentialvarphi/ partial differentialt = L(varphi) + c(x - x)varphi,
      where L is the Kolmogorov forward differential operator commonly used in
      population genetics [i.e., L = (1/2) ( partial differential(2)/ partial
      differentialx(2))V(deltax) - ( partial differential/ partial
      differentialx)M(deltax)], and M(deltax) and V(deltax) stand for the mean and
      variance of the change in x per generation within demes. As to migration, assume
      Wright's island model and denote by m the migration rate per deme per generation.
      By investigating the steady state, in which mutation, migration, random drift,
      and intra- and interdeme selection balance each other, it is shown that the index
      D = c/m - 4N(e)s' serves as a good indicator for predicting which of the two
      forces (i.e., group selection or individual selection) prevails; if D > 0, the
      altruistic allele predominates, but if D < 0, it becomes rare and cannot be
      established in the species.

PMID- 16593384
TI  - Spatial patterns and double diffusion in chemical reactions.
AB  - Spatial ordering has been observed recently during various photochemical
      reactions. Convoluted concentration bands first appear near the surface of
      shallow irradiated solutions. They thereafter extend into the bulk, and finger
      like structures spontaneously develop. We discuss here the possible role of
      double-diffusion effects in the onset of this phenomenon. Indeed, chemical
      reactions occurring near the surface or evaporation of the solvent, or both,
      induce in the bulk adverse gradients of a pair of properties (concentrations of
      solute or concentration and temperature) having different diffusivities. This
      difference can then destabilize the homogeneous solution and trigger the observed
      patterns.

PMID- 16593385
TI  - Primary structure of the M subunit of the reaction center from Rhodopseudomonas
      sphaeroides.
AB  - The reaction center is a membrane-bound bacteriochlorophyll-protein complex that
      mediates the primary photochemical events in the photosynthetic bacterium
      Rhodopseudomonas sphaeroides. The previously determined amino-terminal sequences
      of the three subunits of the reaction center protein were used to design
      synthetic mixed oligonucleotide probes for the structural genes encoding the
      subunits. One of these probes was used to isolate and clone a fragment of DNA
      from R. sphaeroides that contained the gene encoding the M subunit. The
      nucleotide sequence of this gene was determined by the dideoxy method. In
      addition, a number of tryptic and chymotryptic peptides from the M protein were
      isolated and subjected to sequence analysis, and the sequence of the carboxyl
      terminus was determined. Together with the amino-terminal sequence, the data
      establish the primary structure of the M protein. The distribution of hydrophobic
      residues in the amino acid sequence suggests the presence of five membrane
      spanning segments. A significant homology was found between the amino acid
      sequence of the M subunit and a thylakoid membrane protein (M(r) 32,000) from
      spinach that has been implicated in herbicide and quinone binding.

PMID- 16593386
TI  - Alterations in gene expression in sorghum induced by the host-specific toxin from
      Periconia circinata.
AB  - Susceptibility of sorghum to the fungal pathogen Periconia circinata and
      sensitivity to its host-specific toxin are determined by the semidominant allele
      at the pc locus. Pretreatment of susceptible seedlings with cycloheximide or
      cordycepin for 4 hr before treatment with the toxin protected the seedlings
      against toxin-induced loss of electrolytes and prevented development of disease
      symptoms. In vivo incorporation of [(3)H]leucine into protein was inhibited 91%
      and 47% by cycloheximide and cordycepin, respectively, but was not affected by
      the toxin. Gel electrophoresis and fluorography of in vivo-labeled proteins
      extracted from non-treated and toxin-treated root tips of near-isogenic
      susceptible and resistant lines revealed a selective increase in radioactivity of
      a protein band at M(r) 16,000 only in preparations from toxin-treated susceptible
      root tips. Two-dimensional gel electrophoresis separated the M(r) 16,000 band
      into four proteins and confirmed the increased rate of synthesis. Products of in
      vitro translation were substantially enriched with the four M(r) 16,000 proteins
      when total RNA from toxin-treated susceptible root tips was used in a cell-free
      protein-synthesizing system. Because the proteins that increase are common to
      both susceptible and resistant genotypes, the toxin apparently interferes with a
      regulatory function, perhaps a function of the pc locus, and thereby alters gene
      expression in the susceptible genotype. The data suggest but do not establish
      that phytotoxicity results from the increased rate of synthesis of the specific
      proteins.

PMID- 16593387
TI  - Fructose 2,6-bisphosphate and germination of fungal spores.
AB  - Induction of germination of Phycomyces blakesleeanus spores by a heat shock and
      subsequent incubation at 25 degrees C in a glucose- or 6-deoxyglucose-containing
      culture medium resulted in an intense (20-40 times the initial value) rise in the
      concentration of fructose 2,6-bisphosphate and hexose 6-phosphates. The increase
      in the concentration of fructose 2,6-bisphosphate but not that of hexose 6
      phosphates was restricted to a 25-min period during which the spores acquired an
      irreversible capacity to germinate. Incubation of the spores in water for any
      period of time during this critical period resulted in a parallel decrease in
      their ability to form hexose phosphates and to germinate. A similar rise in
      hexose phosphate concentration was also observed when P. blakesleeanus spores
      were activated by incubation in the presence of acetate and also after induction
      of germination of other dormant (Neurospora tetrasperma) or nondormant (Mucor
      racemosus) fungal spores. Extracts of dormant and heat-activated P. blakesleeanus
      spores contain a fructose, 1,6-bisphosphatase that is inhibited by fructose 2,6
      bisphosphate and AMP in a synergistic manner. They also contain a 6-phosphofructo
      2-kinase and a fructose-2,6-bisphosphatase.

PMID- 16593388
TI  - Modifiers of mutation rate: Evolutionary optimum with complete selfing.
AB  - It often has been assumed that, for infinite random mating populations in a
      constant environment, natural selection will favor genotypes at a neutral
      modifier locus that minimize the mutation rate. Mathematical modeling of this
      process confirms this assertion, independent of the selection regime. The same
      model under conditions of complete selfing can produce, under certain
      nondegenerate overdominance conditions, an optimum mutation rate below which
      increased mutation is favored and above which decreased mutation is favored. This
      occurs with unidirectional mutation models and a class of reversible mutation
      models with fitness overdominance. This is the first time that such a modifier
      optimum has been produced analytically for an infinite population in a constant
      environment.

PMID- 16593389
TI  - Biosynthesis of peroxisomal enzymes in the methylotrophic yeast Hansenula
      polymorpha.
AB  - The dramatic expansion of the peroxisomal compartment known to occur in the
      methanol-utilizing yeast Hansenula polymorpha on transfer from glucose- to
      methanol-containing media was shown to be accompanied by the synthesis of at
      least six major polypeptides that dominate the polypeptide pattern of total cell
      extracts analyzed by NaDodSO(4)/polyacrylamide gel electrophoresis. Two of these
      polypeptides have been identified by immunochemical methods as the monomers of
      the peroxisomal enzymes alcohol oxidase and catalase. We have studied the
      biosynthesis of these two peroxisomal enzymes, both by in vitro translation and
      by in vivo labeling experiments. By the criterion of mobility in
      NaDodSO(4)/polyacrylamide gel electrophoresis, the in vitro- and in vivo
      synthesized monomers were indistinguishable from each other, both in the case of
      alcohol oxidase and in that of catalase. Thus, neither of these peroxisomal
      enzymes appear to be synthesized as larger precursors. However, further analysis
      of in vitro-synthesized versus mature peroxisomal alcohol oxidase showed that the
      in vitro-synthesized form sedimented as a 5S monomer and not, like the mature
      peroxisomal enzyme, as a 20S octamer. Moreover, the in vitro-synthesized form was
      highly susceptible to trypsin digestion whereas the mature 20S octamer appeared
      to be resistant.

PMID- 16593390
TI  - Transcription of the white locus in Drosophila melanogaster.
AB  - Genetic studies of the white locus have shown that it has a distal region where
      structural mutations occur and a proximal region where regulatory mutations
      occur. To better understand the molecular basis of this genetic organization we
      have analyzed white locus transcription. A 2.7-kilobase transcript comprising
      0.0005% of poly(A)-RNA was detected in RNA prepared from pupae or adults. The
      structure of this transcript helps clarify some unusual genetic properties of the
      locus. There is a small 5' exon separated from the majority of the sequences
      found in the mature RNA by an intron of approximately 2.8 kilobases. This 5' exon
      is from the proximal region of the locus, whereas the main body of the RNA maps
      to the distal region. The mutationally silent region between the proximal and
      distal regions corresponds to the large intron. We have identified the family and
      determined the exact location of a number of transposable element insertions
      within the locus. These results show that transposable element insertions within
      introns can be without phenotypic effect. We have also investigated the effect on
      the white transcript of the zeste mutation, which represses white locus
      expression as judged by eye color phenotype. The RNA was unchanged in size or
      abundance in poly(A)-RNA from adult flies. This demonstrates that the zeste-white
      interaction does not occur by simply repressing transcription of the white locus
      in all tissues.

PMID- 16593391
TI  - Classes of unitarizable derived functor modules.
AB  - For a real semisimple Lie group G, the description of the unitary dual remains an
      elusive question. One of the difficulties has been the lack of technique for
      constructing unitary representations. Unitary induction from parabolic subgroups
      of G yields unitary representations by the very definition of these
      representations. However, not all unitary irreducible representations of G are
      obtained by this type of induction. In addition, we need derived functor
      parabolic induction [ef. Vogan, D. (1981) Representations of Real Reductive Lie
      Groups (Birkhauser, Boston)] to describe all irreducible representations of G.
      For this second type of induction, the obvious analogues from parabolic subgroup
      induction regarding unitarity are false. In this announcement, we describe a
      setting where derived functor parabolic induction yields unitary representations
      of G. These results include proofs of unitarity for some of the representations
      conjectured to be unitary by Vogan and Zuckerman [(1983) Invent. Math., in press]
      and also proofs of unitarity for some which lie outside the domain described in
      those conjectures.

PMID- 16593392
TI  - Classical geometric resolution of the Einstein-Podolsky-Rosen paradox.
AB  - I show that, in the geometry of a fiber bundle describing a gauge theory,
      curvature and parallel transport ensure and impose nonseparability. The "Einstein
      Podolsky-Rosen paradox" is thus resolved "classically." I conjecture that the
      ostentatiously "implausible" features of the quantum treatment are due to the
      fact that space-time separability, a basic assumption of single-particle
      nonrelativistic quantum mechanics, does not fit the bundle geometry of the
      complete physics.

PMID- 16593393
TI  - Spatial correlation between primary redox components in reaction centers of
      Rhodopseudomonas sphaeroides measured by two electrical methods in the nanosecond
      range.
AB  - Relative distances between the the primary donor P, the intermediary pheophytin
      acceptor H, and the iron-quinone acceptor Q of bacterial reaction centers were
      determined by recording laser flash-induced photovoltages in two experimental
      systems with nanosecond time resolution. In one system a suspension of
      chromatophores was subjected to a light gradient and in the other system
      chromatophores were spread at a heptane/water interface. The 10-ns back reaction
      occurring in reaction centers with reduced Q could be time resolved. The initial
      photovoltage amplitude under conditions in which the charge separation proceeded
      up to the state [P(+)H(-)] was about (2/3) of that when it proceeded up to the
      state [P(+)HQ(-)]. If the amplitude of the photovoltage is considered to be
      proportional to the spatial displacement of charges, this result means that
      pheophytin lies closer to Q than to P.

PMID- 16593394
TI  - Weight gain and adjustment of feeding territory size in migrant hummingbirds.
AB  - Rufous hummingbirds periodically establish and defend territories along their
      summer southward migration route. Using artificial perches attached to spring or
      electronic balances in the field, we were able to measure daily weight changes in
      undistributed, individually marked birds. The territory size (number of flowers)
      of individual birds varied from day to day. Four of five intensively studied
      birds adjusted their territories to that size which was associated with the
      fastest sustained rate of weight gain attained at any stable territory size. The
      one exception was explicable on the basis of its unusually high weight. These
      results are consistent with the assumption of optimization theory that animals
      are capable of assessing when their behavior (e.g., territory size) is suboptimal
      and then making adjustments toward an optimum. The results also suggest, although
      not conclusively, that these birds are selected to maximize their rate of weight
      gain on each stopover prior to resuming migration.

PMID- 16593395
TI  - Fluorescence lifetimes in the bipartite model of the photosynthetic apparatus
      with alpha, beta heterogeneity in photosystem II.
AB  - Recent studies of the lifetime of fluorescence after picosecond pulse excitation
      of photosynthetic organisms revealed relatively complex decay kinetics that
      indicated a sum of three exponential components with lifetimes spanning the range
      from about 0.1-2.5 ns. These fluorescence lifetime data were examined in the
      context of a simple photochemical model for photosystem II that was used
      previously to account for fluorescence yield data obtained during continuous
      illumination. The model, which consists of a single fluorescing species of
      antenna chlorophyll and a reaction center, shows that, in general, the decay
      kinetics after pulse excitation should consist of the sum of two exponential
      decays. The model also shows that in going from open to closed reaction centers
      the lifetime of fluorescence may increase much more than the yield of
      fluorescence and surprisingly long fluorescence lifetimes can be obtained.
      However, conditions can be stated where fluorescence will decay essentially as a
      single component and with lifetime changes that are proportional to the yield
      changes. A heterogeneity was also introduced to distinguish photosystem II(alpha)
      units, which can transfer excitation energy among themselves but not the
      photosystem I, and photosystem II(beta) units, which can transfer energy to
      photosystem I but not to other photosystem II units. It is proposed that the
      rather complex fluorescence lifetime data can be accounted for in large part by
      the simple photochemical model with the alpha, beta heterogeneity in photosystem
      II.

PMID- 16593396
TI  - Biochemical consequences of the insertion of a suppressor-mutator (Spm) receptor
      at the bronze-1 locus in maize.
AB  - Transposition of a receptor element (Rs) for the suppressor-mutator (Spm) has
      generated the first Spm-controlled mutable allele of the bronze-1 (bz) locus in
      maize (Zea mays L.). In the absence of Spm, bz-m13 conditions full anthocyanin
      pigmentation in the aleurone but has a markedly decreased level compared to wild
      type of the gene product, UDPglucose:flavonol 3-O-glucosyltransferase (UFGT; EC
      2.4.1.91). This UFGT activity appears to be qualitatively similar to the wild
      type enzyme. Throughout endosperm development, the amount of a crossreactive
      material far exceeds the amount of detectable UFGT activity. This and other
      observations suggest that this insertion of Rs leads to the production of two
      polypeptides from the bz-m13 allele.

PMID- 16593397
TI  - Enveloped double-stranded DNA insect virus with novel structure and
      cytopathology.
AB  - An unusual type of virus has been isolated from larvae of the cabbage looper,
      Trichoplusia ni (Lepidoptera; Noctuidae). The virus infects a variety of tissues,
      including fat body, epidermis, and tracheal matrix, causing a chronic, fatal
      disease. Viral replication begins in the nucleus and is accompanied by
      invagination of the nuclear envelope and extensive nuclear and cellular
      hypertrophy. The nuclear envelope eventually ruptures and fragments, after which
      viral-induced membranes are assembled along planes through the cell and around
      its periphery. Subsequently, these membranes coalesce, partitioning most of the
      cell, including viroplasms and virions in various stages of assembly, among a
      cluster of vesicles. The vesicles dissociate and are liberated into the hemolymph
      where they accumulate in large numbers (>10(8) vesicles per ml), causing the
      blood to become opaque white. The virus has been isolated from T. ni and
      transmitted per os and by injection to T. ni and several other species of the
      family Noctuidae. The virions produced by this virus are large (ca. 130 x 400
      nm), enveloped, and allantoid in shape with complex symmetry and contain
      apparently linear, double-stranded DNA of M(r) of approximately 1.00 x 10(8). The
      envelope contains subunits arranged in a hexagonal pattern that impart a
      distinctive reticular appearance to virions in negatively stained preparations.
      The unique structural and developmental properties of this virus indicate that it
      is a member of a group of enveloped, double-stranded DNA viruses not observed
      previously.

PMID- 16593398
TI  - Science, technology, and invention: Their progress and interactions.

PMID- 16593399
TI  - Systematic variation of metal-metal bond order in metalloporphyrin dimers.
AB  - A general method for synthesizing a novel class of metalloporphyrin dimers
      containing unbridged metal-metal bonds is presented. By choosing the appropriate
      metal, the bond order in these dimers can be varied systematically. The synthesis
      and characterization of osmium(II) and molybdenum(II) porphyrin dimers containing
      the respective metal-metal double and quadruple bonds are described. A simple
      molecular orbital treatment that accounts for the metal-metal bonding, spin
      state, and geometry in these complexes is discussed.

PMID- 16593400
TI  - Thermodynamics of aqueous sodium chloride to 823 K and 1 kilobar (100 MPa).
AB  - It is shown that a very simple semiempirical equation represents quite accurately
      the thermodynamic properties of aqueous sodium chloride from 373 to 823 K. The
      equation comprises one Margules term and a Debye-Huckel term. Just the one
      Margules parameter is freely adjustable because the Debye-Huckel parameter is
      determined by the properties of water. The equation is valid from the saturation
      composition down to infinite dilution for solvent density above 0.75 g.cm(-3) but
      at lower density only above a solute mole fraction of about 0.1 on an ionized
      basis. Both solute and solvent activity coefficients are fitted from the lowest
      pressure of solution existence up to 1 kilobar (1 bar = 100 kPA). Derivation of
      enthalpy and other related functions is discussed.

PMID- 16593401
TI  - Continuous family of finite-dimensional representations of a solvable Lie algebra
      arising from singularities.
AB  - A natural mapping from the set of complex analytic isolated hypersurface
      singularities to the set of finite dimensional Lie algebras is first defined. It
      is proven that the image under this natural mapping is contained in the set of
      solvable Lie algebras. This approach gives rise to a continuous inequivalent
      family of finite dimensional representations of a solvable Lie algebra.

PMID- 16593402
TI  - Singular integrals related to the Radon transform and boundary value problems.
AB  - Two classes of integral operators are introduced that combine features of
      Calderon-Zygmund singular integrals, the Hilbert integral, and the Radon
      transform. Examples and applications arising from integral geometry and several
      complex variables are discussed.

PMID- 16593403
TI  - Pepsin digestibility of proteins in sorghum and other major cereals.
AB  - We have shown previously that sorghum is highly digestible in the rat. However,
      other workers have shown that sorghum is much less digestible than wheat, maize,
      and rice in young children. Because the rat does not show these digestibility
      differences, we developed an empirical pepsin digestion method, first reported in
      1981, which simulates the digestion values found in children. In this report the
      method has been improved and used to analyze wheat, maize, rice, millet, and
      sorghum and certain processed samples of millet and sorghum. The pepsin digestion
      values parallel those found in children for wheat, maize, rice, and sorghum. In
      addition, a processed sorghum product that gave a high digestion value in
      children also gave a high value with the in vitro pepsin method.

PMID- 16593404
TI  - Bacterio-opsin mRNA in wild-type and bacterio-opsin-deficient Halobacterium
      halobium strains.
AB  - We have examined transcripts corresponding to the Halobacterium halobium bacterio
      opsin (BO) gene in wild-type and in BO-deficient mutant strains containing the
      insertion elements ISH1 or ISH2 in the BO gene. BO mRNA from the wild-type strain
      was purified by hybrid selection using single-stranded cDNA. Labeling by vaccinia
      virus capping enzyme and [alpha-(32)P]GTP showed that it contains the 5'-terminal
      nucleotide of the primary transcript. Sequence analysis showed that transcription
      begins only two nucleotides upstream of the initiator codon for BO. Two species
      of BO mRNA were found; the major species has a ragged 3' terminus approximately
      45 nucleotides downstream from the terminator codon for BO, while the minor
      species is about 170 nucleotides longer at the 3' end. Analysis of the
      transcripts in several BO gene mutant strains by RNA gel-transfer hybridization
      showed that (i) mutants with ISH1 insertions within the NH(2)-terminal coding
      region of the gene contain no detectable transcripts, (ii) mutants with ISH2 near
      the middle of the coding region of the gene contain multiple incomplete
      transcripts, and (iii) a mutant that is partially BO deficient due to an
      insertion of ISH2 100 base pairs upstream of the site of initiation of
      transcription contains a decreased level of BO mRNA.

PMID- 16593405
TI  - Tunneling in Chromatium chromatophores: Detection of a Hopfield charge-transfer
      band.
AB  - We have observed a weak charge-transfer band in the cytochrome c-P(870) electron
      transfer reaction in Chromatium vinosum chromatophores at 10 K and at 85 K.
      First, the intermediate acceptor, I, was trapped in the reduced state by lowering
      the redox potential at room temperature, then illuminating with white light at
      low temperature for 20 min. Next, illumination by broadband infrared (1-3 mum,
      6.5 kW/m(2)) for 4 hr at 10 K decreased the I(-) electron spin resonance signal
      by 30%. One-hour infrared illumination at 85 K decreased the cytochrome c Soret
      band shift by 10%. The effect of infrared was to promote the system from the
      ground vibrational state with the electron on P(870) to an excited vibrational
      state with the electron on cytochrome c. The absorption band peak is near 2 mum,
      and the integrated cross section is approximately 6 x 10(-3) eV.M(-1).cm(-1).
      These values are consistent with small (0.02 nm) nuclear motion and with electron
      transfer rates measured in the dark.

PMID- 16593406
TI  - Reaction center and light-harvesting I genes from Rhodopseudomonas capsulata.
AB  - Five structural genes coding for the reaction center (RC) L, M, and H subunits
      and the two light-harvesting (LH) I polypeptides, B870alpha and B870beta, have
      been mapped on two restriction fragments from the R-prime plasmid pRPS404. It has
      been recently shown that enhanced near-infrared fluorescence mutants of
      Rhodopseudomonas capsulata typically lack RC or LH I polypeptides and that these
      lesions are marker-rescued by two restriction fragments from the R-prime plasmid:
      the 7.5-kilobase-pair EcoRI F fragment and the 4.75-kilobase-pair BamHI C-EcoRI
      fragment. We have now determined the nucleotide sequence of two restriction
      fragments and have found that the BamHI C-EcoRI B fragment carries the structural
      genes for the RC L and M subunits and both LH I polypeptides. Forty kilobase
      pairs away from this locus, the BamHI F fragment (within the EcoRI F fragment)
      carries the RC H subunit. The structural genes on the BamHI C-EcoRI B fragment
      are probably transcribed as part of a polycistronic mRNA. All of the structural
      genes begin with a consensus Shine-Dalgarno sequence and separate AUG start
      codons, indicating that the structural polypeptides are not cleaved from larger
      precursor polypeptides.

PMID- 16593407
TI  - Chloroplast tRNA gene contains a long intron in the D stem: Nucleotide sequences
      of tobacco chloroplast genes for tRNA (UCC) and tRNA (UCU).
AB  - The nucleotide sequences of tobacco chloroplast genes for tRNA(Gly) (UCC) and
      tRNA(Arg) (UCU) have been determined. The tRNA(Gly) gene has a 691-base-pair
      intron located in the D stem while the tRNA(Arg) gene does not have any intron.
      The tRNA(Gly) and tRNA(Arg) genes are encoded on the same strand and separated by
      a 169-base-pair spacer. The tRNA(Gly) gene is transcribed as a 900-base precursor
      RNA molecule. The tRNA(Gly) and tRNA(Arg) deduced from the DNA sequences show 84%
      and 55% sequence homologies with Escherichia coli tRNA(Gly) (UCC) and phage T4
      tRNA(Arg) (UCU), respectively.

PMID- 16593408
TI  - Mn and Co toxicity in chlorophyll biosynthesis.
AB  - The metal ion-induced inhibition of tetrapyrrole biosynthesis was studied in the
      cyanobacterium Anacystis nidulans. The accumulation of protoporphyrin and Mg
      protoporphyrin due to the effect of Co(2+) and Mn(2+) treatment, respectively,
      pointed to two different sites of inhibition.

PMID- 16593409
TI  - Drift and mutation with a finite number of allelic states.
AB  - The frequencies with which alleles are alike within (Q) and between (q)
      populations are formulated for monoecious populations undergoing drift and
      mutation with unequal mutation rates among alleles for a finite number (k) of
      allelic states. The effective number of alleles and an application to Nei's
      measure of genetic distance [Nei, M. (1972) Am. Nat. 106, 283-292] are also
      considered for this model. The equilibrium values of Q and q increase as k
      decreases. Unequal mutation rates further increase the equilibrium values and
      reduce the rates of approach of Q and q to these values. The transitional values
      of Q and q are very dependent on the initial population frequency composition
      when mutation rates are unequal. Reducing k, of course, reduces the effective
      number of alleles, which is further reduced by unequal mutation rates.
      Complications introduced by initial population composition, unequal mutation
      rates, and number of allelic states, coupled with data limitations for long-term
      measures of genetic distance or population differentiation, with mutation as the
      main driving force, are discussed.

PMID- 16593410
TI  - Cross-polarization/magic-angle sample-spinning C NMR spectroscopic study of
      chlorophyll a in the solid state.
AB  - Solid-state cross-polarization/magic-angle sample-spinning (13)C NMR spectra have
      been recorded on chlorophyll a-water aggregates, methyl pyrochlorophyllide a, and
      methyl pyropheophorbide a (derivatives that lack a phytyl chain). Spectra have
      also been collected under a decoupling regime in which resonances of certain
      hydrogen-bearing carbon atoms are suppressed. These observations are used to
      assign the solid-state spectra.

PMID- 16593411
TI  - Laplace operators of infinite-dimensional Lie algebras and theta functions.
AB  - Until recently, the generalized Casimir operator constructed by Kac [Kac, V. G.
      (1974) Funct. Anal. Appl. 8, 68-70] has been the only known element of the center
      of a completion of the enveloping algebra of a Kac-Moody algebra. It has been
      conjectured [Deodhar, V. V., Gabber, O. & Kac, V. G. (1982) Adv. Math. 45, 92
      116], however, that the image of the Harish-Chandra homomorphism contains all
      theta functions defined on the interior of the complexified Tits cone and hence
      separates the orbits of the Weyl group. Developing the ideas of Feigin and Fuchs
      [Feigin, B. L. & Fuchs, D. B. (1983) Dokl. Akad. Nauk SSSR 269, 1057-1060], I
      prove this conjecture. Another application of this method is the Chevalley type
      restriction theorem for simple finite-dimensional Lie superalgebras.

PMID- 16593412
TI  - Sensitive light scattering probe of enzymatic processes in retinal rod
      photoreceptor membranes.
AB  - Light excitation of as little as 0.05% of the rhodopsin in a retinal rod membrane
      suspension reduces the near-IR optical transmission by 25%. This transmission
      decrease requires the presence of guanosine triphosphate, is opposite in sign and
      25 times larger in amplitude than a GTP-dependent light-scattering signal
      previously reported in rod outer segment suspensions [Kuhn, H., Bennett, N.,
      Michel-Vallez, M. & Chabre, M. (1981) Proc. Natl. Acad. Sci. USA, 78, 6873-6877],
      and is kinetically complex. The initial phase of the optical transmission
      decrease begins after about a 50-ms lag (at 0.05% bleach) and has a first-order
      time constant of 300-500 ms. The scattering signal returns to the preactinic
      baseline in a time dependent on the amount of GTP added. A nonhydrolyzable GTP
      analogue, guanylyl imidodiphosphate, produces a scattering signal that does not
      return to the preactinic baseline. Adenosine triphosphate strongly inhibits the
      return of the GTP-dependent transmission decrease to the preactinic baseline.
      This effect of ATP on the GTP signal apparently requires ATP hydrolysis because
      it is inhibited by the simultaneous presence of adenylyl imidodiphosphate, a
      nonhydrolyzable analogue of ATP. The light-scattering signal and the velocity of
      the activation of a rod outer segment phosphodiesterase saturate when >0.05% of
      the rhodopsin is bleached and both show nearly identical dependence on light
      stimulus. It is suggested that these nucleotide-dependent light-scattering
      signals arise from changes in the state of membrane aggregation that are
      controlled by enzymatic processes. This hypothesis is supported by the large
      amplitude of the signals, sedimentation experiments, and a strong membrane
      concentration dependence. The ATP effects can be rationalized within the above
      hypothesis as being due to ATP-dependent rhodopsin phosphorylation that adds
      negative charges to the membrane surface and tends to keep the membranes
      disaggregated. An additional signal, which increases light transmission, is
      produced by a second, much more intense flash. The latter signal is interpreted
      as the result of proton binding by bleached rhodopsin molecules that decreases
      the negative charge repulsion between the membranes and allows increased
      aggregation.

PMID- 16593413
TI  - Some plant leaves have orientation-dependent EPR and NMR spectra.
AB  - Proton nuclear magnetic resonance ((1)H NMR) spectra of leaves from 50 plant
      species were obtained at a spectrometer frequency of 470 MHz. Water present in
      leaf samples gives rise to characteristic spectral patterns. Most species show
      only one broad (1)H NMR peak; however, the leaves of some plants display complex,
      orientation-dependent spectra in which a common three-line pattern is discerned.
      The pattern varies with the angle between the leaf surface and the external
      magnetic field. Proton relaxation measurements show the presence of at least two
      water compartments in the leaves. The compartments are responsible for different
      components of the spectral pattern. EPR spectra, obtained at 35 GHz and at a
      temperature of -180 degrees C, of plant leaf sections are dominated by the strong
      signals of manganous ions. We find that most plant leaves have isotropic Mn(2+)
      EPR spectra. However, in some species (including ones that exhibit orientation
      dependent (1)H NMR spectra) we detect orientation-dependent intensities in the
      forbidden lines; the spectra indicate that Mn(2+) ions occupy binding sites with
      axial or lower symmetry on nonrandomly oriented membranes. Both the NMR and the
      EPR results suggest that the chloroplasts of some plants are preferentially
      aligned with respect to the leaf surface.

PMID- 16593414
TI  - Spider sedation induced by defensive chemicals of milliped prey.
AB  - Wolf spiders (Lycosa spp.) show delayed induced sedation (total immobilization)
      of prolonged duration (in the order of days) after attacks upon millipeds
      (Glomeris marginata). The sedation is specifically attributable to glomerin and
      homoglomerin, two previously characterized quinazolinones present in the
      defensive secretion of Glomeris. Median sedative doses for the quinazolinones are
      in the range of 1-7 mug per spider, a fraction of the total (60-90 mug) present
      in the secretion of medium to full-grown millipeds. A sedative effect upon an
      invertebrate predator has not previously been demonstrated for an animal defense.
      Quinazolinones include the synthetic drug methaqualone (Quaalude), a potent human
      sedative.

PMID- 16593415
TI  - Snail shape and growth rates: Evidence for plastic shell allometry in Littorina
      littorea.
AB  - The periwinkle Littorina littorea exhibits morphological variation among southern
      New England populations that appear to be genetically continuous. In dense
      populations, individuals have relatively elongate shells in comparison to
      individuals in sparse populations, which have rounder, globose shells. We
      experimentally demonstrate that this shell variation is a function of snail
      growth rate. Rapidly growing snails develop thin, globose shells that accommodate
      more body mass than thicker, more elongate shells. The implications of these
      results are discussed in relation to interpreting morphological variation in
      extant gastropods and in the molluscan fossil record.

PMID- 16593416
TI  - An immune strain of Halobacterium halobium carries the invertible L segment of
      phage PhiH as a plasmid.
AB  - The structure of the circular prophage genome of PhiH varies with high frequency
      in single colony progeny of the defective lysogen Halobacterium halobium R(1)-3.
      As in linear PhiH DNA, a segment flanked by two copies of the insertion element
      ISH1.8 is inverted frequently. This L segment can also circularize to a plasmid
      of 12 kilobase pairs with simultaneous loss of the remaining phage DNA. Strain
      R(1)-L, which contains this plasmid, is immune to phage infection. A phage
      variant, PhiHL1, is able to grow on R(1)-L and carries an insertion of 1 kilobase
      pair in its L segment. PhiHL1 does not grow on normal lysogens. This shows that
      the plasmid confers to R(1)-L only part of the immunity of normal lysogens.

PMID- 16593417
TI  - Electron nuclear double resonance evidence supporting a monomeric nature for P700
      in spinach chloroplasts.
AB  - Proton electron nuclear double resonance (ENDOR) spectra of P700(+) in spinach
      chloroplasts and in photosystem I particles have been obtained and compared with
      the corresponding ENDOR spectrum of monomeric chlorophyl a(+) (Chla(+)) cation
      radical. The hyperfine couplings for P700(+) can be interpreted in terms of those
      expected for a monomer Chla(+) radical. The reduction in alpha-carbon spin
      densities observed for the in vivo species when compared to the in vitro radical
      is attributed to differences in the composition of the ground-state orbital for
      the two systems. For P700(+), a mixture of 75% D(0)/25% D(1), in which D(0) and
      D(1) represent the ground-and first excited-state orbitals calculated by Petke et
      al. for Chla(+) [Petke, J. D., Maggiora, G. M., Shipman, L. L. & Christoffersen,
      R. E. (1980) Photochem. Photobiol. 31, 243-257], gives good agreement between
      calculated and experimental spin-density reduction factors. Interaction of the
      pigment ion with its protein environment such as through ligation of the central
      Mg atom, hydrogen bonding to the 9-keto-carbonyl group, and electrostatic
      interactions with charged amino acid residues are proposed as factors responsible
      for the lowering in energy of the D(1) level in vivo. Combined with similar
      previous proposals for P680(+) of photosystem II, the data suggest that both
      primary donor cation radicals of green plant photosynthesis can be viewed as
      monomeric Chla(+) species in which the D(1) orbital makes a significant
      contribution to the spin-density distribution.

PMID- 16593418
TI  - Induction of phenylalanine ammonia-lyase and 4-coumarate:CoA ligase mRNAs in
      cultured plant cells by UV light or fungal elicitor.
AB  - The mRNAs encoding two enzymes of phenylpropanoid metabolism, phenylalanine
      ammonia-lyase (PAL; EC 4.3.1.5) and 4-coumarate:CoA ligase (4CL; EC 6.2.1.12),
      were induced in cultured parsley cells (Petroselinum hortense) either by
      irradiation with UV light or by treatment with elicitor, a cell-wall fraction of
      the fungus Phytophthora megasperma f. sp. glycinea. Two-dimensional gel
      electrophoresis of the encoded PAL and 4CL proteins revealed that the mRNAs
      induced by either treatment were very similar if not identical. RNA blot
      hybridization with cDNAs complementary to these mRNAs was used to measure changes
      in the mRNA amounts at various times after either treatment. Total cellular PAL
      and 4CL mRNA amounts increased coordinately after UV irradiation to a maximum at
      7 hr and then decreased to uninduced levels by 30 hr with the same kinetics as
      observed previously for the changes in the translational activities. Treatment
      with the fungal elicitor also caused coordinated, but more rapid, changes in PAL
      and 4CL mRNA translational activities, with a sharp peak occurring 3 hr after the
      addition of elicitor. Corresponding changes in mRNA amounts were observed only
      for 4CL, whereas the amount of PAL mRNA continued to increase at least up to 20
      hr after elicitor addition. Our results suggest that parsley cells respond to UV
      irradiation or addition of fungal elicitor by increased rates of transcription of
      genes involved in the synthesis of compounds related to UV or disease resistance,
      respectively.

PMID- 16593419
TI  - Charge accumulation and photochemistry in leaves studied by thermoluminescence
      and delayed light emission.
AB  - A major breakthrough in our understanding of how plants oxidize water to
      molecular O(2) was the discovery by P. Joliot and co-workers that the O(2) yield
      per flash, in a series of light flashes, oscillates with a periodicity of 4. This
      led to the concept by B. Kok and co-workers that these reactions involve
      accumulation of four positive charges in independent "O(2)-evolving centers,"
      which undergo a series of changes in their redox state (the so-called S states).
      In the present paper, we have applied optical techniques (such as
      thermoluminescence and delayed light emission, both discovered by W. Arnold and
      co-workers) to monitor charge storage on the O(2)-evolving system in leaves from
      higher plants. We observed a period of four oscillations in both
      thermoluminescence and delayed light emission, with maxima on flashes 2 and 6,
      establishing a relationship with the charge accumulation process in
      photosynthesis. These measurements provided additional new information: the
      deactivation of the "O(2)-evolving centers," which cannot be measured by the O(2)
      method in the leaves, is in the 20- to 30-s range; and in the dark-adapted
      leaves, the secondary bound plastoquinone molecule (the so-called secondary
      electron acceptor Q(B)) is in equal concentration in its reduced and oxidized
      forms. The origin of thermoluminescence and delayed light emission, in terms of
      the recombination of charges on the O(2)-evolving and plastoquinone sides, is
      also discussed.

PMID- 16593420
TI  - Demonstration of transcriptional regulation of specific genes by phytochrome
      action.
AB  - We have developed an in vitro transcription system that uses nuclei isolated from
      Lemna gibba G-3. The in vitro transcripts include sequences homologous to
      hybridization probes for the small subunit of ribulose-1,5-bisphosphate
      carboxylase [3-phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39], the
      light-harvesting chlorophyll a/b-protein, and rRNA. Light-harvesting chlorophyll
      a/b-protein sequences are transcribed to a greater extent in nuclei isolated from
      plants grown in darkness with 2 min of red light every 8 hr than in nuclei
      isolated from dark-treated plants. Furthermore, the amount of these transcripts
      measured in plants given a single minute of red light after dark treatment is
      increased over the amount measured in dark-treated plants. The effect of red
      light is at least partially reversible by 10 min of far-red light given
      immediately after the red light pulse. Transcription of both rRNA and small
      subunit sequences is also stimulated by a single minute of red light as compared
      to dark-treated tissue. However, the relative magnitudes of the increases
      compared to the dark levels are smaller than the increase seen for the
      chlorophyll a/b-protein, possibly because of the higher level of transcription of
      these sequences in the dark. The effect of red light on the transcription of
      small subunit and rRNA sequences is also reversible by immediate treatment with
      10 min of far-red light. Pulse chase studies of dark-treated nuclei for up to 110
      min do not show substantial turnover of in vitro labeled small subunit and
      chlorophyll a/b-protein transcripts. We therefore conclude that phytochrome
      action has induced specific changes in transcription of these genes.

PMID- 16593421
TI  - Chloroplast DNA recombination in interspecific hybrids of Chlamydomonas: Linkage
      between a nonmendelian locus for streptomycin resistance and restriction
      fragments coding for 16S rRNA.
AB  - Differences in the distribution of Ava I and BstEII restriction sites in the
      chloroplast DNA (cpDNA) of Chlamydomonas eugametos and C. moewusii have been used
      to detect extensive cpDNA recombination in the hybrid progeny of these
      interfertile algae. In the present study, the inheritance of these restriction
      site differences was tested for recombination with nonmendelian genetic markers
      for resistance to streptomycin and erythromycin in interspecific crosses and in
      hybrid backcrosses to C. moewusii. Most of the restriction-pattern markers appear
      linked to the antibiotic-resistance markers, thus supporting the chloroplast
      localization of the resistance markers. The streptomycin marker, in particular,
      shows perfect coordinate inheritance with an Ava I band containing one cpDNA
      fragment and a BstEII band containing two comigrating cpDNA fragments. Molecular
      hybridization experiments using DNA from the Ava I band as a probe show sequence
      homology between this DNA, the two comigrating BstEII fragments, and cpDNA
      fragments from C. reinhardtii containing the genes for 16S rRNA. The results show
      the feasibility of using C. eugametos-C. moewusii hybrids to identify cpDNA
      sequences that either contain or are closely linked to nonmendelian genetic
      markers.

PMID- 16593422
TI  - Mercury selection of allozymes in marine organisms: Prediction and verification
      in nature.
AB  - The geographic distributions of mercury-tolerant allozyme genotypes of the enzyme
      phosphoglucomutase in the shrimp Palaemon elegans and the enzyme phosphoglucose
      isomerase in the marine gastropod Monodonta turbinata were compared in a mercury
      polluted site versus several unpolluted sites on the Israeli coast of the
      Mediterranean sea. We conclude that in both phosphoglucomutase and phosphoglucose
      isomerase, the level of the mercury-tolerant allozyme genotypes was higher in the
      polluted as compared with the unpolluted sites. These results suggest that
      mercury selection is operating in nature on allozyme genotypes of these marine
      organisms along patterns comparable with those found previously in laboratory
      experiments. We suggest that the enzymes studied here display an adaptive pattern
      in polluted environments. Therefore, they may be used as potential indicators and
      monitors of marine pollution.

PMID- 16593423
TI  - Critical phenomena and thermodynamics of dilute aqueous sodium chloride to 823 K.
AB  - Semiempirical equations are developed that represent the behavior of dilute
      solutions of NaCl in water (steam) in the range 723-823 K where ion pairing is
      extensive. This supplements the equations given earlier for more concentrated
      solutions. In this temperature range the system NaCl/H(2)O shows critical
      behavior with two phases below the critical pressure. The equations for the
      dilute solutions yield critical behavior. Though the equations for concentrated
      solutions do not yield critical behavior at the critical pressure, only a very
      small interpolation function is required to connect smoothly the two equations.
      The ion-pairing equilibrium constants are reported as well as the Gibbs energies
      of hydration for both ions and ion pairs.

PMID- 16593424
TI  - Indefinite intertwining operators.
AB  - For a wide class of linear connected semisimple Lie groups, one obtains formulas
      limiting the Langlands parameters of irreducible unitary representations obtained
      from maximal parabolic subgroups. The formulas relate unitarity to the number of
      roots satisfying certain conditions. Some evidence is presented that the formulas
      are sharp. The results confirm aspects of conjectures that relate unitary
      parameters to cohomological induction.

PMID- 16593425
TI  - Escape from strange repellers.
AB  - In a dynamical system described by a map, it may be that a "strange" sets of
      points is left invariant under the mapping. The set is a repeller if points
      placed in its neighborhood move away. An escape rate is defined to describe this
      motion. An alternative method of evaluating the escape rate, based on the
      consideration of repulsive cycles, is proposed. In the several cases examined
      numerically and analytically, the escape rate is shown to agree with the proposed
      formula.

PMID- 16593426
TI  - On the Williams-Watts function of dielectric relaxation.
AB  - It has been observed over the past 15 years that experimental frequency-dependent
      dielectric constants of broad classes of materials including polymeric systems
      and glasses may be interpreted in terms of the Williams-Watts polarization decay
      function [Formula: see text] The exponent alpha and the time constant T depend on
      the material and fixed external conditions such as temperature and pressure. We
      derive this form of varphi(alpha)(t) from the following random-walk model.
      Suppose that an electric field has been applied for some time to a medium
      containing many polar molecules (or polar groups in complex molecules) and the
      direction of their dipole moments remains frozen as the field is removed.
      Furthermore, suppose that the medium contains mobile defects that on reaching the
      site of a frozen dipole relax the medium to the degree that the dipole may
      reorient itself. If the diffusion of defects toward dipoles is executed as a
      continuous-time random walk composed of an alternation of steps and pauses and
      the pausing-time distribution function has a long tail of the form psi(t)
      infinity t(-1-alpha), then the relaxation function has the above fractional
      exponential form.

PMID- 16593427
TI  - Regulation of protein metabolism: Coupling of photosynthetic electron transport
      to in vivo degradation of the rapidly metabolized 32-kilodalton protein of the
      chloroplast membranes.
AB  - In Spirodela oligorrhiza, mature chloroplasts copiously synthesize and degrade a
      32-kilodalton membrane protein. The rates of synthesis and degradation are
      controlled by light intensity, the protein being unstable in the light and stable
      in the dark. Light-driven synthesis, but not degradation, is dependent on ATP.
      Degradation is blocked by herbicides inhibiting photosystem II electron
      transport, such as diuron and atrazine. Thus, both anabolism and catabolism of
      the 32-kilodalton protein are photoregulated, with degradation coupled to
      electron transport rather than phosphorylation.

PMID- 16593428
TI  - Structural studies of the primary donor cation radical P(870) in reaction centers
      of Rhodospirillum rubrum by electron-nuclear double resonance in solution.
AB  - The light-induced cation radical of the primary electron donor, P(870) (+.), in
      photosynthetic reaction centers from Rhodospirillum rubrum G-9, has been
      investigated by electron-nuclear double resonance (ENDOR) in liquid aqueous
      solution. The measured hyperfine coupling constants are assigned to specific
      molecular positions by partial deuteration. Comparison with the
      bacteriochlorophyll a cation radical shows different reduction factors of the
      individual coupling constants deviating from the value 2.0 reported in earlier
      investigations in frozen solutions. The average of the coupling constants is,
      however, reduced by a factor very close to 2.0. EPR simulations using the ENDOR
      coupling constants support a dimer model for P(870) (+.) with C(2) symmetry,
      where the two macrocycles are close enough to form a supermolecular orbital
      resulting in a different distribution of the unpaired electron, compared with the
      monomeric bacteriochlorophyll a cation radical. Molecular orbital calculations
      were used to obtain structural information about this dimer.

PMID- 16593429
TI  - Crambin in phospholipid vesicles: Circular dichroism analysis of crystal
      structure relevance.
AB  - Crambin, a hydrophobic plant seed protein that exhibits sequence homology to
      membrane-active plant toxins, was incorporated into phospholipid vesicles.
      Circular dichroism spectroscopy indicates that its structure in vesicles is
      nearly identical to its structure in 60% ethanol solution, the solvent from which
      the protein was crystallized. The secondary structure predicted from the circular
      dichroism data of the ethanol solution closely resembles that determined by x-ray
      diffraction of the crystals. This agreement suggests that the x-ray structure may
      form a useful basis for modeling the structure and behavior of lipophilic plant
      toxins. Finally, because the structure of crambin has been determined in an
      organic solvent medium, it provides a protein standard for examination of the
      effect of solvent dipole moment on the circular dichroism spectra of proteins,
      which may be important for interpretation of data for membrane proteins.

PMID- 16593430
TI  - Tubulins from different higher plant species are immunologically nonidentical and
      bind colchicine differentially.
AB  - We have initiated immunological and drug-binding studies on the tubulins from
      different higher plant species. Antibodies were raised against
      electrophoretically separated rose (Rosa sp.) tubulin alpha- and beta-subunits
      and characterized by immunoblot autoradiographic assays. Each IgG preparation
      bound to its antigen and cross-reacted differentially with the respective tubulin
      subunits from an alga, sea urchin, rabbit, and cow. Antigenic determinants were
      shared more among the beta-subunits than among the alpha-subunits from these
      organisms. Tubulins were isolated from cultured cells of carrot (Daucus carota)
      and hibiscus (Hibiscus rosa-senensis). Immunoautoradiography and quantitation of
      cross-reactivity on blots showed nonidentity among homologous subunits from rose,
      carrot, hibiscus, and alga tubulins, with more antigenic differences among alpha
      subunits than among beta-subunits. Comparative colchicine-binding assays showed
      that rose and hibiscus tubulins bound 33% and 65%, respectively, of the
      colchicine bound by carrot tubulin and that higher plant tubulins bound much less
      colchicine than bovine brain tubulin under identical conditions.

PMID- 16593431
TI  - Balbiani ring induction in phosphate metabolism.
AB  - Balbiani rings (BR), giant puffs in Chironomus larval salivary glands, code for
      giant secretory proteins. As shown earlier, the normally dominant BR2 is turned
      off with its putative translation product during exposure of larvae to compounds
      that diminish the stores of P(i). A BR6 develops from a compact chromosome band,
      and a new giant protein appears in the secretion as the major component. We have
      determined the sequence of cloned DNA fragments representative for large parts of
      BR1 and BR2 (normally active) and the inducible BR6. There is an excess of
      positive charges and high contents of serine/threonine in the coded amino acid
      composition for the BR1 and BR2 sequences. The coded amino acid sequence for the
      BR6 clone shares homologies with the others but has an excess of negative charges
      and lacks serine/threonine. This suggested that the P(i) effects observed earlier
      could be related to differences in phosphorylation between the normal proteins
      and the BR6 product. This could be confirmed by measurements of phosphorylation,
      which occurs in the normal giant proteins mainly at seryl residues. P export with
      giant secretory protein is normally quantitatively important. Thus, BR6
      activation should decrease P loss when P(i) pools are lowered because of inducer
      action.

PMID- 16593432
TI  - Hormonal control of eclosion of flies from the puparium.
AB  - Pharate flies (Sarcophaga bullata) very close to eclosion were injected with
      hemolymph from eclosing flies or various other preparations, kept at 10 degrees C
      for 24 hr, returned to room temperature, and tested for eclosion behavior
      (ongoing, attempted, or completed eclosion) during the first 30 min, the
      subsequent 2(1/2) hr, and after 51 hr. Flies injected with "eclosion" hemolymph
      showed significantly more eclosion activity during the first 30 min than
      noninjected controls, flies injected with hemolymph from larvae, or flies
      injected with Ringer solution.

PMID- 16593433
TI  - Rhizobium free-living nitrogen fixation occurs in specialized nongrowing cells.
AB  - A model for free-living N(2) fixation by Rhizobium sp. RC3200 is presented that
      asserts that this process occurs in nongrowing cells. Cultures containing mixed
      populations of cell types, N(2)-fixing and vegetative, grow cooperatively. In
      nitrogen-limited liquid suspension cultures, cooperative growth occurs by means
      of ammonium that is produced and exported by nongrowing, N(2)-fixing cells and
      transported to vegetative cells. This model implies prokaryotic differentiation:
      the creation of metabolically specialized cells, terminally nonviable, that
      functionally cooperate in a higher cell order. Here, the switch to a Rhizobium
      N(2)-fixing cell state is regulated by both O(2) and utilizable nitrogen.

PMID- 16593434
TI  - Evidence that phosphorylation and dephosphorylation regulate the distribution of
      excitation energy between the two photosystems of photosynthesis in vivo:
      Photoacoustic and fluorimetric study of an intact leaf.
AB  - State 1-state 2 transitions in an intact tobacco leaf were monitored by the
      photoacoustic method. Modulated oxygen evolution yield and its enhancement by
      continuous far-red light ("Emerson enhancement") were used to characterize the
      balance of light distribution between the two photosystems. These measurements
      were additionally supported by fluorimetry. Adaptation of the leaf to far-red
      light (lambda [unk] 700 nm), mainly absorbed in photosystem I (light 1), results
      in state 1, where short-wavelength light (light 2) is distributed in favor of
      photosystem II. This is shown by a low yield of oxygen evolution, a high extent
      of Emerson enhancement, a concomitantly high extent of fluorescence quenching by
      far-red light, and a low ratio of the 77 K emission peaks at 730 and 695 nm. The
      magnitudes of these parameters were reversed when the leaf was adapted to light 2
      (state 2), indicating a change towards a more equal distribution of the
      excitation between the two photosystems. Preincubation of an intact leaf with
      NaF, a specific phosphatase inhibitor, stimulated the extent of adaptation to
      light 2, shown by all the above criteria, and completely abolished adaptation to
      light 1. Light 1 preillumination prior to NaF treatment resulted initially in
      state 1, but then a transition to state 2 was irreversibly induced by any light.
      The NaF effect was specific because NaCl did not affect the state 1-state 2
      transitions. Leaching out the NaF restored the original physiological transitions
      of the leaf. NaF presumably acts here in the same way as it acts in isolated
      thylakoids-by blocking the dephosphorylation of membranal proteins (particularly
      the chlorophyll a/b-protein complex) phosphorylated by a light 2-activated
      kinase. Our results give direct support to the suggestion [Allen, J. F., Bennett,
      J., Steinback, K. E. & Arntzen, C. J. (1981) Nature (London) 291, 25-29] that it
      is the phosphorylation level of thylakoid proteins that controls the light
      distribution between the two photosystems in vivo, shown previously in isolated
      thylakoids.

PMID- 16593435
TI  - Chloroplast DNA transcripts are encapsidated by tobacco mosaic virus coat
      protein.
AB  - Preparations of tobacco mosaic virus contain pseudovirions, particles resembling
      virions but containing host rather than viral RNA. The encapsidated host RNA was
      found to be composed of discrete-sized species derived from a large portion of
      the chloroplast genome except that very little, if any, ribosomal RNA is present.
      Pseudovirions contain the same chloroplast DNA transcripts as those detected in
      extracts from uninfected leaves, although not always in the same relative
      amounts. Several strains of tobacco mosaic virus were tested and all were found
      to contain pseudovirions, with the U2 strain containing more than the others.

PMID- 16593436
TI  - Lipid peroxidation forms ethylene from 1-aminocyclopropane-1-carboxylic acid and
      may operate in leaf senescence.
AB  - An enzyme system is described which oxidizes 1-aminocyclopropane-1-carboxylic
      acid (ACC) to ethylene under physiological conditions. It comprises linoleic
      acid, pyridoxal phosphate, manganese, and lipoxygenase (linoleate:oxygen
      oxidoreductase, EC 1.13.11.12). It requires oxygen and is specific for manganese;
      it can operate but only with greatly reduced yield in the absence of pyridoxal
      phosphate. An enzyme with the same properties was prepared from microsomal
      membranes of the seedling shoots of peas. Both have similar reactions to a
      variety of inhibitors and other reagents. The properties also resemble those of
      at least two of the in vivo systems recorded in the literature. Intact green oat
      leaves also contain a similar system. Because there is a growing body of evidence
      that ethylene formation is associated with cell membranes and because the yields
      of ethylene from the complete system are much higher than those recorded for
      other enzymes, it may be identical with the in vivo system acting in senescent
      leaves.

PMID- 16593437
TI  - On the evolution of altruism by kin selection.
AB  - A general model for the evolution of altruism is formulated. Central to the model
      is a pair of local fitness functions, which prescribe the fitness of the altruist
      and selfish phenotypes as functions of the composition of local groups into which
      prereproductives are subdivided. When the local groups are sibships or other kin
      groups, the model is one for kin selection. Functions for cost and benefit of
      altruism are derived from the fitness functions. Conditions for evolution of
      altruism are then determined in terms of cost and benefit. It is shown that the
      Hamilton rule has quantitative validity only in the special case of linear
      fitness functions. Sufficient conditions are found for qualitative validity of
      the Hamilton rule. Qualitative violation of the rule is also possible.

PMID- 16593438
TI  - The pre-melt phase of n-alkanes: Crystallographic evidence for a kinked chain
      structure.
AB  - Electron diffraction measurements on epitaxially grown crystals of orthorhombic n
      hexatriacontane, n-C(36)H(74), give evidence for the chain-defect mechanism for
      linear chain melting. The derived structural model is also in accord with recent
      spectroscopic studies of odd-chain n-alkanes, and the diffraction data
      specifically exclude models based on helices or rigid chain rotors. Stability of
      a kinked chain structure, moreover, is indicated by an observed hysteresis effect
      that gives different pretransition temperatures for solution-grown and annealed
      crystals.

PMID- 16593439
TI  - Evidence from bond lengths and bond angles for enneacovalence of cobalt, rhodium,
      iridium, iron, ruthenium, and osmium in compounds with elements of medium
      electronegativity.
AB  - Enneacovalence of neutral atoms can be achieved for Co, Rh, and Ir by promoting
      some electrons from the nd orbital to the (n + 1)s and (n + 1)p orbitals and for
      Fe, Ru, and Os by a similar promotion together with the addition of an electron,
      which may be provided by an electron pair from a singly bonded carbonyl group or
      other group. The bond lengths and bond angles are predicted by the theory of
      enneacovalence to be significantly different for the different transition metals.
      Recently reported experimental values are shown to be in good agreement with the
      predicted values, providing support for the theory of enneacovalence and the
      theory of hybrid sp(3)d(5) bond orbitals.

PMID- 16593440
TI  - Yields of Soviet underground nuclear explosions from seismic surface waves:
      Compliance with the Threshold Test Ban Treaty.
AB  - Magnitudes of the larger Soviet underground nuclear weapons tests from the start
      of the Threshold Test Ban Treaty in 1976 through 1982 are determined for short-
      and long-period seismic waves. Yields are calculated from the surface wave
      magnitude for those explosions at the eastern Kazakh test site that triggered a
      small-to-negligible component of tectonic stress and are used to calibrate body
      wave magnitude-yield relationship that can be used to determine the sizes of
      other explosions at that test site. The results confirm that a large bias,
      related to differential attenuation of P waves, exists between Nevada and Central
      Asia. The yields of the seven largest Soviet explosions are nearly identical and
      are close to 150 kilotons, the limit set by the Threshold Treaty.

PMID- 16593441
TI  - On some applications of diophantine approximations.
AB  - Siegel's results [Siegel, C. L. (1929) Abh. Preuss. Akad. Wiss. Phys.-Math. Kl.
      1] on the transcendence and algebraic independence of values of E-functions are
      refined to obtain the best possible bound for the measures of irrationality and
      linear independence of values of arbitrary E-functions at rational points. Our
      results show that values of E-functions at rational points have measures of
      diophantine approximations typical to "almost all" numbers. In particular, any
      such number has the "2 + epsilon" exponent of irrationality: Theta - p/q > q(-2
      epsilon) for relatively prime rational integers p,q, with q >/= q(0) (Theta,
      epsilon). These results answer some problems posed by Lang. The methods used here
      are based on the introduction of graded Pade approximations to systems of
      functions satisfying linear differential equations with rational function
      coefficients. The constructions and proofs of this paper were used in the
      functional (nonarithmetic case) in a previous paper [Chudnovsky, D. V. &
      Chudnovsky, G. V. (1983) Proc. Natl. Acad. Sci. USA 80, 5158-5162].

PMID- 16593442
TI  - Extensive and widespread homologies between mitochondrial DNA and chloroplast DNA
      in plants.
AB  - We used hybridization techniques to demonstrate that numerous sequence homologies
      exist between cloned mung bean and spinach chloroplast DNA (ctDNA) restriction
      fragments and mtDNAs from corn, mung bean, spinach, and pea. The strongest cross
      homologies are between clones derived from the ctDNA inverted repeat and mtDNA
      from corn and pea, although all the ctDNA clones tested hybridized to at least
      one mtDNA restriction fragment. Known chloroplast genes showing strong mtDNA
      homologies include those for the large subunit of ribulosebisphosphate
      carboxylase, which hybridizes to corn mtDNA, and the beta subunit of the
      chloroplast ATPase, which hybridizes to mung bean mtDNA. Certain of these
      homologies were confirmed by using cloned spinach mtDNA restriction fragments as
      probes in reciprocal hybridizations to ctDNA. Several of these ctDNA-homologous
      mtDNA sequences were shown to be much more closely related to ctDNA from the same
      species than to that of a distantly related species. We interpret these
      differential homologies as evidence for relatively recent DNA sequence transfer
      events, suggesting that transpostion between the two genomes is an ongoing
      evolutionary process.

PMID- 16593443
TI  - Purification of cowpea mosaic virus RNA replication complex: Identification of a
      virus-encoded 110,000-dalton polypeptide responsible for RNA chain elongation.
AB  - An endogenous cowpea mosaic virus (CPMV) RNA-protein complex (CPMV replication
      complex) capable of elongating in vitro preexisting nascent chains to full-length
      viral RNAs has been solubilized from the membrane fraction of CPMV-infected
      cowpea leaves using Triton X-100 and purified by Sepharose 2B chromatography and
      glycerol gradient centrifugation in the presence of Triton X-100. Analysis of the
      polypeptide composition of the complex by NaDod-SO(4)/PAGE and silver staining
      revealed major polypeptides with molecular masses of 110, 68, and 57 kilodaltons
      (kDa), among which the 110-kDa polypeptide was consistently found to cosediment
      precisely with the RNA polymerase activity. Using antisera to specific viral
      proteins, we found the 110-kDa polypeptide to be the only known viral polypeptide
      associated with the RNA replication complex, the 68- and 57-kDa polypeptides
      being most probably host-specific. The host-encoded 130-kDa monomeric RNA
      dependent RNA polymerase, which is known to be stimulated in CPMV-infected cowpea
      leaves, did not copurify with the virus-specific RNA polymerase complex. Our
      results dispute the hypothesis that plant viral RNA replication may be mediated
      by the RNA-dependent RNA polymerase of uninfected plants. We tentatively conclude
      that the 110-kDa polypeptide encoded by the bottom component RNA of CPMV
      constitutes the core of the CPMV RNA replication complex.

PMID- 16593444
TI  - Formaldehyde activation factor, tetrahydromethanopterin, a coenzyme of
      methanogenesis.
AB  - An oxygen-labile formaldehyde activation factor (FAF) was isolated in highly
      purified form by use of anoxic fractionation procedures. The molecular weight of
      FAF was determined to be 776 and that of methanopterin (MPT) 772 by fast-atom
      bombardment mass spectrometry (FABMS). High-resolution FABMS measurements on MPT
      and FAF indicated molecular formulas of C(30)H(41)N(6)O(16)P and
      C(30)H(45)N(6)O(16)P, respectively. The presence of phosphorus was confirmed by
      100-MHz (31)P NMR. The 360-MHz (1)H NMR spectrum of FAF in deuterium oxide was
      similar to that of MPT. A functional relationship between MPT and FAF was
      documented; both compounds stimulated the reductive demethylation of 2
      (methylthio)ethanesulfonic acid (CH(3)-S-CoM) to CH(4) when formaldehyde
      oxidation provided a source of electrons, and FAF replaced MPT in the CH(3)-S-CoM
      stimulated conversion of CO(2) to CH(4) under H(2) (the RPG effect). MPT was
      enzymically converted to FAF during the reduction of CH(3)-S-CoM, and HCHO to
      CH(4) under H(2). Evidence indicates that FAF is tetrahydromethanopterin.

PMID- 16593445
TI  - Determination of retinal Schiff base configuration in bacteriorhodopsin.
AB  - Resonance Raman spectra of the BR(568), BR(548), K(625), and L(550) intermediates
      of the bacteriorhodopsin photocycle have been obtained in (1)H(2)O and (2)H(2)O
      by using native purple membrane as well as purple membrane regenerated with 14,15
      (13)C(2) and 12,14-(2)H(2) isotopic derivatives of retinal. These derivatives
      were selected to determine the contribution of the C(14)-C(15) stretch to the
      normal modes in the 1100- to 1400-cm(-1) fingerprint region and to characterize
      the coupling of the C(14)-C(15) stretch with the NH rock. Normal mode
      calculations demonstrate that when the retinal Schiff base is in the C[unk]N cis
      configuration the C(14)-C(15) stretch and the NH rock are strongly coupled,
      resulting in a large ( approximately 50-cm(-1)) upshift of the C(14)-C(15)
      stretch upon deuteration of the Schiff base nitrogen. In the C[unk]N trans
      geometry these vibrations are weakly coupled and only a slight (<5-cm(-1))
      upshift of the C(14)-C(15) stretch is predicted upon N-deuteration. In BR(568),
      the insensitivity of the 1201-cm(-1) C(14)-C(15) stretch to N-deuteration
      demonstrates that its retinal C[unk]N configuration is trans. The C(14)-C(15)
      stretch in BR(548), however, shifts up from 1167 cm(-1) in (1)H(2)O to 1208 cm(
      1) in (2)H(2)O, indicating that BR(548) contains a C[unk]N cis chromophore. Thus,
      the conversion of BR(568) to BR(548) (dark adaptation) involves isomerization
      about the C[unk]N bond in addition to isomerization about the C(13)[unk]C(14)
      bond. The insensitivity of the native, [14,15-(13)C(2)]-, and [12,14
      (2)H(2)]K(625) and L(550) spectra to N-deuteration argues that these
      intermediates have a C[unk]N trans configuration. Thus, the primary photochemical
      step in bacteriorhodopsin (BR(568) --> K(625)) involves isomerization about the
      C(13)[unk]C(14) bond alone. The significance of these results for the mechanism
      of proton-pumping by bacteriorhodopsin is discussed.

PMID- 16593446
TI  - Calmodulin inhibitor in senescing apples and its physiological and
      pharmacological significance.
AB  - While assaying calmodulin activity in senesced apple extracts by using its
      property of promoting the activity of activator-deficient 3',5'-cyclic AMP 5'
      nucleotidohydrolase (phosphodiesterase, EC 3.1.4.17) from bovine heart, we
      detected a heat-stable, dialyzable, low molecular weight component that inhibited
      calmodulin activity. Specific activity of calmodulin as calculated from the
      linearly increasing portion of the activity curve was in the range of 150 to 160
      units/mg of protein in crude extracts from apples stored at 2 degrees C for a
      period of 6 months with or without calcium treatment. Apple extract that was
      passed through a phenothiazine-Sepharose affinity column did not promote
      phosphodiesterase activity, whereas the EGTA eluate of the column promoted
      phosphodiesterase activity similar to the original extract. The inhibition of
      calmodulin activity appeared to be lower in extracts from apples stored at 2
      degrees C after calcium treatment. The inhibition was found to increase after
      storage of apples at room temperature for 30 days. Activity of purified bovine
      brain calmodulin was also inhibited by the inhibitor present in apple extracts,
      which indicated that the inhibition was not specific to plant calmodulin alone
      and could have wide applications. The importance of the inhibitor in relation to
      senescence/aging and its possible pharmacological applications are discussed.

PMID- 16593447
TI  - Photoreduction of ferredoxin with various electron donors: Support for the Z
      scheme of photosynthetic electron transport.
AB  - The currently accepted scheme for photosynthetic electron flow from water to
      ferredoxin (and subsequently to NADP), known as the Z scheme, envisions a linear
      electron flow that requires two photosystems joined by several electron carriers.
      The observation that the extent of photoreduction of ferredoxin depends on
      whether electrons are provided by water (a donor to photosystem II) or by
      artificial electron donors to photosystem I led Arnon et al. [Arnon, D. I.,
      Tsujimoto, H. Y. & Tang, G. M.-S. (1980) Proc. Natl. Acad. Sei. USA 77, 2676
      2680] to question the validity of the Z scheme for photosynthetic electron
      transport. Our results show that this difference is not due to any inherent
      difference in electron transport but to the fact that when electron donors are
      added to chloroplasts they oxidize (in their oxidized state) reduced ferredoxin.
      Different electron donors oxidize reduced ferredoxin to a different extent;
      dehydroascorbate is a more potent oxidant than dithiothreitol. Dichlorophenol
      indophenol is also a potent oxidant of reduced ferredoxin. The rate of NADP
      reduction and the K(m) for NADP with various electron donors reflect the
      oxidative capacities of the electron donors and mediators. These results also
      explain the fact that NADP reduction with electron donors to photosystem I is
      less than that with water, despite the fact that electron flow from donor to
      artificial dyes can proceed at high rates.

PMID- 16593448
TI  - cAMP pulses coordinate morphogenetic movement during fruiting body formation of
      Dictyostelium minutum.
AB  - Aggregation in the primitive cellular slime mold Dictyostelium minutum proceeds
      by means of chemotaxis toward a continuously secreted folic acid analog [De Wit,
      R. J. W. & Konijn, T. M. (1983) Cell Differ. 12, 205-210]. The onset of
      culmination is marked by the appearance of concentric waves of cell movement on
      the aggregate surface. Culmination proceeds by the chemotactic attraction of
      amoebae to the center of wave propagation, which results in the accumulation of
      amoebae into a finger-like structure. Evidence is presented that the
      chemoattractant used during culmination is cAMP, which is secreted in pulses. The
      cells secrete cAMP themselves; cAMP receptors and phosphodiesterase activity
      appear on the cell surface just before the onset of culmination. Micromolar
      concentrations of externally applied cAMP induce disorientation of amoeboid
      movement at the onset of culmination. These observations are compatible with the
      hypothesis that the cAMP signaling system organizes multicellular development in
      both primitive and advanced cellular slime mold species. Advanced species such as
      Dictyostelium discoideum use this signaling system also in an earlier stage of
      development to organize the process of cell aggregation.

PMID- 16593449
TI  - Differential cellular distribution of cAMP-dependent protein kinase during
      development of Dictyostelium discoideum.
AB  - It was shown previously by us that cAMP-dependent protein kinase activity in the
      cellular slime mold Dictyostelium discoideum increased during the early stages of
      development. Results from other laboratories showed that during the subsequent
      stage of cell differentiation and positioning, the accumulation of a number of
      prespore mRNAs and proteins (but not prestalk mRNAs and proteins) was dependent
      upon cAMP. The present communication describes the cellular distribution of the
      cAMP-dependent protein kinase at that stage of development. Pseudoplasmodia were
      disrupted, and prespore cells were separated from prestalk cells by sedimentation
      through a Percoll gradient. Prespore cells had approximately 4-5 times as much of
      both the catalytic and regulatory subunits of the cAMP-dependent protein kinase
      as did the prestalk cells. That the increase of cAMP-dependent protein kinase
      during development reflected de novo synthesis of the enzyme in both prespore and
      prestalk cells was demonstrated on the basis of [(3)H]leucine incorporation into
      the regulatory subunit. The findings are consistent with a role of the cAMP
      dependent protein kinase in mediating the effects of cAMP on the synthesis of
      prespore-specific mRNAs and proteins at the stage at which cAMP appears to be
      required for the cell type-specific syntheses.

PMID- 16593450
TI  - Molecular genetics of a biological clock in Drosophila.
AB  - Ninety kilobase pairs (kb) of DNA have been isolated from the 3B region of the X
      chromosome of Drosophila melanogaster. Previous cytogenetic analyses have placed
      a gene required for rhythmic behavior (per) in this chromosomal interval.
      Physical characterization of a series of chromosomal rearrangements altering per
      locus activity indicates that DNA affecting behavioral rhythms is found in a 7.1
      kb HindIII fragment. A single 4.5-kb poly(A)(+) RNA is transcribed from this DNA
      in wild-type pupae and adult flies. The transcript is eliminated by a per mutant
      that retains some rhythmic activity, but this mutant substitutes two novel
      transcripts, 11.5 kb and 0.9 kb. It is suggested that the new poly(A)(+)
      transcripts provide residual per locus activity.

PMID- 16593451
TI  - Lignin-degrading enzyme from Phanerochaete chrysosporium: Purification,
      characterization, and catalytic properties of a unique H(2)O(2)-requiring
      oxygenase.
AB  - An extracellular lignin-degrading enzyme from the basidiomycete Phanerochaete
      chrysosporium Burdsall was purified to homogeneity by ion-exchange
      chromatography. The 42,000-dalton ligninase contains one protoheme IX per
      molecule. It catalyzes, nonstereospecifically, several oxidations in the alkyl
      side chains of lignin-related compounds: C(alpha)-C(beta) cleavage in lignin
      related compounds of the type aryl-C(alpha)HOH-C(beta)HR-C(gamma)H(2)OH (R = 
      aryl or -O-aryl), oxidation of benzyl alcohols to aldehydes or ketones, intradiol
      cleavage in phenylglycol structures, and hydroxylation of benzylic methylene
      groups. It also catalyzes oxidative coupling of phenols, perhaps explaining the
      long-recognized association between phenol oxidation and lignin degradation. All
      reactions require H(2)O(2). The C(alpha)-C(beta) cleavage and methylene
      hydroxylation reactions involve substrate oxygenation; the oxygen atom is from
      O(2) and not H(2)O(2). Thus the enzyme is an oxygenase, unique in its requirement
      for H(2)O(2).

PMID- 16593452
TI  - Specific amino acid substitutions in bacterioopsin: Replacement of a restriction
      fragment in the structural gene by synthetic DNA fragments containing altered
      codons.
AB  - To study the mechanism of light-dependent proton translocation by
      bacteriorhodopsin, we have introduced single-codon changes in the gene so as to
      produce the following specific amino acid substitutions in the protein: Tyr-185
      to Phe, Pro-186 to Leu, Trp-189 to Phe, Ser-193 to Ala, and Glu-194 to Gln. The
      strategy involved replacement of a 62-base-pair restriction fragment by synthetic
      DNA duplexes containing the modified nucleotide sequences. This required a unique
      restriction site (Xho I) at Ile-203 which was created by oligonucleotide-directed
      point mutagenesis. The six DNA duplexes corresponding to the modified native and
      mutant restriction fragments were all prepared by DNA ligase-catalyzed joining of
      chemically synthesized deoxyribooligonucleotides. The bacterioopsin expression
      plasmids reconstructed by using the synthetic DNA fragments were characterized by
      restriction analysis and DNA sequence determination. An extremely rapid,
      efficient, and general method for purification of the synthetic oligonucleotides
      and of DNA fragments was developed.

PMID- 16593453
TI  - Molecular cloning of cDNA for Avena phytochrome.
AB  - We have isolated several cDNA clones for phytochrome, a plant regulatory
      photoreceptor. A cDNA library was constructed by using etiolated Avena poly(A)(+)
      RNA enriched for phytochrome mRNA by size fractionation. Replicate arrays of
      colonies were differentially screened with cDNA probes made from poly(A)(+) RNA
      that had been either enriched in or depleted of phytochrome mRNA. Of the colonies
      hybridizing preferentially with the enriched probe, several contained plasmids
      that specifically selected phytochrome mRNA when assayed by hybridization
      selection and translation. The largest such plasmid, pAP-2, was used to isolate
      clones from an Avena genomic library. One of these genomic clones was then used
      to screen a second cDNA library in an attempt to identify full-length phytochrome
      clones. The largest of the plasmids thus obtained, pAP-3, contains a 3.4
      kilobasepair (kbp) insert, verified to contain phytochrome sequences by
      hybridization-selection and translation. Sequence analysis of pAP-2 and pAP-3
      revealed that the two clones are identical in sequence through a 2.4-kbp region
      in which they overlap. However, the pAP-2 insert contains, in addition, 1.5 kbp
      of sequence of unknown origin, the apparent result of a recombination event.
      Blots of poly(A)(+) RNA hybridized with (32)P-labeled pAP-2 or pAP-3 show a
      single mRNA band at 4.2 kilobases. Blot analysis of RNA from dark-grown and from
      red-irradiated tissue demonstrates that a previously reported light-induced
      decrease in translatable phytochrome mRNA results from a decrease in physical
      abundance of this mRNA.

PMID- 16593454
TI  - Purification and properties of a pea chloroplast DNA polymerase.
AB  - A DNA polymerase has been purified >3,000-fold from the chloroplasts of pea
      plants by chromatography on DEAE-cellulose, phosphocellulose, single-stranded DNA
      agarose, and sedimentation in a glycerol gradient. Electrophoretic analysis on
      polyacrylamide gels in the presence of sodium dodecyl sulfate indicates that the
      final fraction contained a single discernible protein band of 90,000 daltons. Gel
      filtration on Sephacryl S-200 and glycerol gradient sedimentation under
      nondenaturing conditions demonstrate that the chloroplast DNA polymerase has a
      native molecular mass of approximately 87,000 daltons. The purified polymerase
      lacks any associated nuclease activity. The enzyme activity is inhibited by N
      ethylmaleimide (74% at 1.0 mM) and ethidium bromide (90% at 0.23 mM) and is
      resistant to aphidicolin. The purified enzyme is totally dependent on the
      presence of added DNA, has an absolute requirement for Mg(2+) (12 mM optimal), is
      stimulated by K(+) (120 mM optimal), and requires all four deoxynucleoside
      triphosphates for maximum activity. Native DNA which has been degraded to a
      limited extent with DNase I is the most efficient template.

PMID- 16593455
TI  - Effects of Cu deficiency on photosynthetic electron transport.
AB  - The role of copper (Cu) in photosynthetic electron transport was explored by
      using Cu deficiency in sugar beet as an experimental approach. Copper influenced
      electron transport at two sites in addition to plastocyanin. Under mild
      deficiency (0.84 nmol of Cu per cm(2) of leaf area), electron transport between
      the two photosystems (PS) is inhibited but not electron transport within PS I or
      PS II measured separately. The chlorophyll/plastoquinone ratio was normal in Cu
      deficient plants. However, the breakpoint in the Arrhenius plot of electron
      transport was shifted towards a higher temperature. It is concluded that Cu is
      necessary to maintain the appropriate membrane fluidity to ensure the mobility of
      plastoquinone molecules to transfer electrons between the two photosystems. Under
      severe deficiency (0.22 nmol of Cu per cm(2) of leaf area) both PS II and PS I
      electron transports were inhibited and to the same extent. PS II electron
      transport activity could not be restored by adding artificial electron donors.
      Polypeptides with M(r)s of 28,000 and 13,500 were missing in Cu-deficient
      chloroplast membranes. In PS II particles prepared from normal chloroplasts of
      spinach, 2 atoms of Cu per reaction center are present. We conclude that Cu
      influences PS II electron transport either directly, by participation in electron
      transfer as a constituent of an electron carrier, or indirectly, via the
      polypeptide composition of the membrane in the PS II complex.

PMID- 16593456
TI  - Chemically defined media for cultivation of Naegleria gruberi.
AB  - Cultivation of amebae of the axenic strain of Naegleria gruberi, NEG-M, was
      achieved in media consisting entirely of chemically defined components. A
      complete medium that contains 31 components allows growth with yields up to 5 x
      10(6) amebae per ml. A minimal medium gives lower yields but defines 22
      components that are essential for continuous cultivation: 11 amino acids, 6
      vitamins, hematin, guanosine, D-glucose, Mg(2+), and inorganic phosphate. These
      media allow precise studies of the metabolism and differentiation of this unusual
      eukaryote.

PMID- 16593457
TI  - Branch-specific heterosynaptic facilitation in Aplysia siphon sensory cells.
AB  - Aplysia siphon sensory cells exhibit heterosynaptic facilitation of transmitter
      release during both sensitization and classical conditioning of the siphon
      withdrawal response. In the present study, we asked whether facilitation must
      invariably enhance transmission at all terminals of a neuron or whether
      facilitation can instead occur at one set of terminals without also occurring at
      other terminals of the same cell. To examine this question, we compared effects
      of local application of serotonin and of connective stimulation on transmission
      at central and peripheral branches of single sensory cells. We found that
      heterosynaptic facilitation can be branch-specific and can occur at either
      central or peripheral synapses independently. We also found that siphon sensory
      cells exhibit homosynaptic post-tetanic potentiation, allowing us to compare
      effects of hetero- and homosynaptic facilitation in the same cells. By contrast
      to heterosynaptic facilitation, homosynaptic facilitation occurs concomitantly at
      both central and peripheral synapses of siphon sensory cells. Thus, while both
      heterosynaptic and homosynaptic facilitation involve increases in transmitter
      release from sensory neuron terminals, heterosynaptic facilitation provides a
      greater specificity and flexibility in the modification of synaptic connections.

PMID- 16593458
TI  - Model calculations of the interaction of two parallel antiaromatic 4n pi-electron
      systems.
AB  - The nature of the interaction between decks of a pentalene dimer and an s
      indacene dimer has been studied by semi-empirical MNDO/1 and MINDO/3 calculations
      for distances between decks of from 5 A to 2 A. In contradiction to qualitative
      predictions from a frontier orbital analysis, it is found that the 4n-4n pi
      electron interaction between decks for such dimers is destabilizing for distances
      exceeding about 2.5 A.

PMID- 16593459
TI  - Rotational barrier of a molybdenum-molybdenum quadruple bond.
AB  - The synthesis and characterization of molybdenum(II) porphyrin dimers containing
      unbridged metal-metal quadruple bonds are presented. Variable temperature 300 MHz
      (1)H NMR studies of meso-substituted derivatives provide novel solution evidence
      for both the existence of quadruple bonds and for a barrier to rotation about the
      metal-metal bonds in these complexes. The activation energy for this rotational
      process is 10.1 +/- 0.5 kcal.mol(-1).

PMID- 16593460
TI  - Dirac operators coupled to vector potentials.
AB  - Characteristic classes for the index of the Dirac family [unk](A) are computed in
      terms of differential forms on the orbit space of vector potentials under gauge
      transformations. They represent obstructions to the existence of a covariant
      Dirac propagator. The first obstruction is related to a chiral anomaly.

PMID- 16593461
TI  - Structure and expression of a pea nuclear gene encoding a chlorophyll a/b-binding
      polypeptide.
AB  - A nuclear gene AB80 has been isolated from a phage lambda Charon 4 library of pea
      DNA. The sequence of the gene has been determined and it has been shown to
      contain an uninterrupted reading frame of 269 amino acids, corresponding to a
      precursor to a constituent polypeptide of the light-harvesting chlorophyll a/b
      protein complex. Primer extension and S1 nuclease studies defined a cap site for
      AB80. The first methionine codon 3' from this site is 69 nucleotides away and is
      the initiating codon of the open reading frame. A "TATA" sequence occurs 31
      nucleotides 5' from the cap site. A second TATA sequence is found 7 nucleotides
      on the 5' side of the initiating methionine codon and the sequences surrounding
      this TATA sequence are strikingly similar to those surrounding the first TATA
      sequence. The mature polypeptide encoded by AB80 differs by 5 amino acids from
      the polypeptide corresponding to a previously characterized cDNA sequence pAB96.
      This result is indicative of heterogeneity within the constituent polypeptides of
      the light-harvesting chlorophyll a/b-protein complex. The sequence Arg-Lys-Ser
      Ala-Thr-Thr-Lys-Lys occurs at, or near, the NH(2)-terminus of the mature
      polypeptide encoded by AB80. This basic peptide is of interest because of its
      apparent involvement in changes in excitation-energy distribution in chloroplast
      membranes. Some general similarities, but no extensive sequence homology, is
      found on comparing the transit sequence for the precursor to the chlorophyll a/b
      binding polypeptide with the transit sequences previously determined for the
      precursors to the small subunit of ribulose-1,5-bisphosphate carboxylase.

PMID- 16593462
TI  - Characterization and postulated structure of the primary emitter in the bacterial
      luciferase reaction.
AB  - An intermediate identifiable as the emitter in bacterial bioluminescence has been
      demonstrated. The reaction was carried out at 1 degrees C by mixing purified
      luciferase-bound FMN 4a-hydroperoxide with long-chain aldehyde (decanal).
      Simultaneous kinetic measurements of bioluminescence and absorbance showed that
      the decay of light emission occurred more rapidly than the appearance of the
      stable product, oxidized FMN, indicating the formation of a transient
      intermediate species subsequent to light emission. The same species was found in
      reaction mixtures examined immediately after light emission was completed. It has
      a relatively short half-life (7 min at 9 degrees C); the chromophore is
      postulated to be the luciferase-bound flavin 4a-hydroxide and to decay to the
      stable product, FMN, by losing water. Both its absorption spectrum (lambda(max),
      360 nm) and its fluorescence emission (lambda(max), 490 nm) are consistent with
      the hypothesis that this is the ground state of the primary emitter, the
      bioluminescent species produced in the reaction.

PMID- 16593463
TI  - Formation of cyanide from carbon 1 of 1-aminocyclopropane-1-carboxylic acid
      during its conversion to ethylene.
AB  - It has been shown that 1-aminocyclopropane-1-carboxylic acid (ACC) is the
      immediate precursor of ethylene, which is derived from C-2 and C-3 of ACC. When
      [1-(14)C]ACC was administered to etiolated mungbean (Vigna radiata) hypocotyls,
      approximately 16% of the ACC was converted to ethylene and about 10% of the
      radioactivity was converted to [(14)C]asparagine in 7 hr. In etiolated epicotyls
      of common vetch (Vicia sativa), after 7 hr about 14% of the ACC was converted to
      ethylene and 16% of the radioactivity was converted to beta-cyanoalanine plus
      gamma-glutamyl-beta-cyanoalanine. Itis known that in most plants cyanide is
      metabolized to asparagine via the intermediate beta-cyanoalanine, whereas in a
      fewplants such as V. sativa, beta-cyanoalanine is converted to the conjugate
      gamma-glutamyl-beta-cyanoalanine. We confirmed that [(14)C]cyanide was
      metabolized into [(14)C]asparagine in mungbean and into [(14)C]cyanoalanine plus
      its conjugate in V. sativa. Moreover, after feeding plant tissue with [1
      (14)C]ACC, [(14)C]asparagine isolated from mungbean and beta-[(14)C]cyanoalanine
      from V. sativa were labeled in the C-4 position, as would be expected if these
      two compounds were derived from [(14)C]cyanide. When the conversion of ACC to
      ethylene in V. sativa tissue was inhibited by high temperature (41 degrees C),
      the conversion of [1-(14)C]ACC to beta-[(14)C]cyanoalanine and gamma-glutamyl
      beta-[(14)C]cyanoalanine was similarly inhibited. When [carboxyl-(14)C]ACC was
      administered to mungbean and V. sativa, (14)CO(2) was recovered in an amount
      equivalent to the amount of ethylene produced. These data indicate that in the
      conversion of ACC to ethylene the carboxyl group yields CO(2), and C-1 is
      released as HCN.

PMID- 16593464
TI  - Cooperative transient trapping of photosystem II protons by the integral membrane
      portion (CF0) of chloroplast ATP-synthase after mild extraction of the four
      subunit catalytic part (CF1).
AB  - The ATP-synthase in chloroplasts is built from two blocks, CF0, which is integral
      to the thylakoid membrane and which serves as a proton channel, and CF1, attached
      to CF0, which is catalytically active. This study is aimed at understanding
      proton conduction through CF0. By a mild procedure we extracted <10% of total
      CF1, predominantly the four-subunit CF1 without the delta subunit. Extracted
      chloroplasts were excited with short flashes of light and the time course of the
      transmembrane potential and of the pH changes in both phases was measured
      spectrophotometrically. Mild extraction of CF1 caused two effects. (i) Up to 50%
      of the protons rapidly released from water oxidation transiently escaped
      detection in the thylakoid interior. (ii) The initial extent of the transmembrane
      potential was decreased by some 10% (20-mus resolution). Protons that were not
      detected inside appeared in the external phase after having passed the thylakoid
      membrane. pH titrations of the transient loss of protons produced an extremely
      sharp transition (near pH 7.5) as if six protons were buffered in a strictly
      cooperative manner. These effects were reversed upon addition of N,N'
      dicyclohexylcarbodiimide, which, among other actions, blocks the proton channel
      through CF0. We interpret these observations as follows. (i) CF0 incorporates
      proton binding groups, which can act in a hexacooperative way. These groups are
      located near the middle of the membrane. (ii) After extraction of CF1, protons
      produced during water oxidation have very rapid access to these groups, but they
      pass the full span of the membrane more slowly: buffering precedes conduction
      through CF0.

PMID- 16593465
TI  - Plasmid-linked nif and "nod" genes in fast-growing rhizobia that nodulate Glycine
      max, Psophocarpus tetragonolobus, and Vigna unguiculata.
AB  - Forty-nine fast-growing Rhizobium strains from the nodules of 26 different
      tropical legume genera were screened to find isolates that would (i) nodulate,
      e.g., winged beans, so producing large nodules for RNA and protein isolation;
      (ii) also nodulate various small-seeded legumes, thus allowing screening of large
      numbers of mutants; and (iii) harbor plasmids containing nif structural genes as
      well as other functions involved in nodulation. On the basis of six different
      criteria, this rhizobial group appeared intermediate between classical fast- and
      slow-growing organisms, yet all contained plasmids. Plasmid numbers varied from
      one to five. Hybridizations between DNA prepared from nifDH and the putatative
      "nod" region of R. meliloti and these plasmids bound to nitrocellulose filters
      suggested that nif-nod genes are linked on a single sym plasmid. A broad-host
      range strain containing a single sym plasmid was chosen for further study. Its
      plasmid, pMPIK3030a, was isolated on cesium chloride gradients and cloned in the
      cosmid pJB8, and the overlapping fragments were mapped by homology with the nif
      and nod regions of R. meliloti. As the wild-type plasmid pMPIK3030a was not self
      transmissible, confirmation that the nod genes detected by homology were
      responsible for nodulation was obtained by introducing the mobilization functions
      of RP(4) (together with Tn5) and selecting transconjugants resistant to kanamycin
      and neomycin. Transconjugants (obtained at a frequency of about 10(-6) per
      recipient) in Agrobacterium tumefaciens cured of the Ti plasmid produced
      ineffective nodules on Vigna unguiculata, those in nonnodulating (Nod(-)) R.
      meliloti were partially effective, while those in Nod(-)R. leguminosarum were
      often fully effective.

PMID- 16593466
TI  - Synaptic stimulation alters protein phosphorylation in vivo in a single Aplysia
      neuron.
AB  - Protein phosphorylation was examined in the identified Aplysia neuron R15, in
      vivo, after the intracellular injection of [gamma-(32)P]ATP. Two-dimensional gel
      electrophoretic analysis indicates that at least 70 proteins are phosphorylated
      within R15 during a 50-min labeling period. Application of serotonin (5HT)
      results in an increase in K(+) conductance in R15 and a concomitant change in the
      phosphorylation pattern: there are increases or decreases in the phosphorylation
      of some proteins, and at least five phosphoproteins appear that are not observed
      in control cells. Dopamine causes a decrease in voltage-dependent inward
      conductance in R15 and also alters the phosphorylation pattern: several of the
      phosphorylation changes are similar to those produced by 5HT, while others are
      unique to dopamine. Stimulation of the branchial nerve leading to the abdominal
      ganglion results in a long-lasting synaptic hyperpolarization of R15. The
      conductance changes underlying this response include an increase in K(+)
      conductance (identical to that produced by 5HT) together with a decrease in
      voltage-dependent inward conductance (identical to that produced by dopamine).
      The phosphorylation changes induced in R15 by branchial nerve stimulation
      resemble a combination of the changes induced by 5HT and dopamine. The results
      demonstrate that synaptic stimulation can modulate the phosphorylation of
      specific proteins in a single identified postsynaptic neuron and are consistent
      with the hypothesis that protein phosphorylation can regulate the regulate the
      activity of neuronal ion channels.

PMID- 16593467
TI  - Periodic structures in lipid monolayer phase transitions.
AB  - Periodic patterns are observed when supported lipid monolayers doped with low
      concentrations of fluorescent lipid probes are observed with epi-fluorescence
      microscopy. Monolayers of dipalmitoyl phosphatidylcholine were examined on air
      water interfaces and also on alkylated glass coverslips. The patterns are formed
      by periodic arrays of solid-phase lipid domains in equilibrium with fluid-phase
      lipid under specified conditions of temperature and two-dimensional lipid
      pressure. Electrostatic forces may stabilize the periodic ordering of the solid
      domains.

PMID- 16593468
TI  - Radial Fourier multipliers of L(R).
AB  - We give sufficient conditions (in terms of differentiability and growth
      properties) for a radial function to be an L(p)(R(2)) Fourier multiplier. These
      conditions are in the nature of best possible.

PMID- 16593469
TI  - A natural representation of the Fischer-Griess Monster with the modular function
      J as character.
AB  - We announce the construction of an irreducible graded module V for an "affine"
      commutative nonassociative algebra [unk]. This algebra is an "affinization" of a
      slight variant [unk] of the commutative nonassociative algebra B defined by
      Griess in his construction of the Monster sporadic group F(1). The character of V
      is given by the modular function J(q) = q(-1) + 0 + 196884q +.... We obtain a
      natural action of the Monster on V compatible with the action of [unk], thus
      conceptually explaining a major part of the numerical observations known as
      Monstrous Moonshine. Our construction starts from ideas in the theory of the
      basic representations of affine Lie algebras and develops further the calculus of
      vertex operators. In particular, the homogeneous and principal representations of
      the simplest affine Lie algebra A(1) ((l)) and the relation between them play an
      important role in our construction. As a corollary we deduce Griess's results,
      obtained previously by direct calculation, about the algebra structure of B and
      the action of F(1) on it. In this work, the Monster, a finite group, is defined
      and studied by means of a canonical infinite-dimensional representation.

PMID- 16593470
TI  - Structure of the Hf nucleus in high rotational states.
AB  - The values of the moment of inertia of the ground-state band of (168)Hf from J =
      0(+) to 22(+) are interpreted as involving a revolving cluster with composition
      increasing steadily from p(10.5)n(14) to p(20.5)n(24), with radius of revolution
      6.390 fm. The excited bands from 14(+) to 34(+), 21(-) to 33(-), and 18(-) to 30(
      ) have nearly the same very large moment of inertia. It is interpreted as
      involving two caps, each consisting of 11 tritons, on opposite sides of the
      nearly doubly magic sphere p(50)n(52), the value of the radius of revolution
      being 6.445 fm.

PMID- 16593471
TI  - Differential induction of chalcone synthase mRNA activity at the onset of
      phytoalexin accumulation in compatible and incompatible plant-pathogen
      interactions.
AB  - Changes in the mRNA activity of chalcone synthase, the first enzyme of
      phenylpropanoid metabolism specific to flavonoid/isoflavonoid biosynthesis, have
      been investigated in relation to expression of the phytoalexin defense response
      in race-cultivar specific interactions between hypocotyls of Phaseolus vulgaris
      and the partially biotrophic fungus Colletotrichum lindemuthianum, causal agent
      of anthracnose. In an incompatible interaction (host resistant) there is an early
      but localized increase in chalcone synthase mRNA activity prior to the onset of
      accumulation of the phenylpropanoid-derived phytoalexin phaseoflin and expression
      of hypersensitive resistance. In contrast, in a compatible interaction (host
      susceptible) there is no induction of mRNA activity in the early stages of
      infection but rather a delayed, widespread increase during attempted lesion
      limitation at the onset of symptom development. The data indicate that control of
      phytoalexin gene expression is a key early component in the defense responses of
      biologically stressed cells during a race-cultivar specific host-pathogen
      interaction.

PMID- 16593472
TI  - Herbicide resistance in Chlamydomonas reinhardtii results from a mutation in the
      chloroplast gene for the 32-kilodalton protein of photosystem II.
AB  - We report the isolation and characterization of a uniparental mutant of
      Chlamydomonas reinhardtii that is resistant to 3-(3,4-dichlorophenyl)-1,1
      dimethylurea (DCMU) and 2-chloro-4-ethylamino-6-isopropylamino-s-triazine
      (atrazine). Such herbicides inhibit photosynthesis by preventing transfer of
      electrons in photosystem II from the primary stable electron acceptor Q to the
      secondary stable electron acceptor complex B, which is thought to contain a
      protein of 32 kDa and a bound quinone. It has been proposed that herbicide
      binding to the 32-kDa protein alters the B complex so that electron transfer from
      Q is prohibited. Both whole and broken-cell preparations of the mutant alga show
      a resistance to the effects of herbicide on electron transfer from Q to B, as
      measured by fluorescence-induction kinetics. In the absence of herbicide, mutant
      cells exhibit a slower rate of Q to B electron transfer than do wild-type cells.
      The 32-kDa protein from wild-type cells, but not mutant cells, binds
      azido[(14)C]atrazine at 0.1 muM. We have isolated psbA, the chloroplast gene for
      the 32-kDa protein, from both wild-type and herbicide-resistant algae and
      sequenced the coding regions of the gene that are contained in five exons. The
      only difference between the exon nucleotide sequences of the wild-type and mutant
      psbA is a single T-A to G-C transversion. This mutation results in a predicted
      amino acid change of serine in the wild-type protein to alanine in the mutant. We
      suggest that this alteration in the 32-kDa protein is the molecular basis for
      herbicide resistance in the C. reinhardtii mutant.

PMID- 16593473
TI  - Active-site carbamate formation and reaction-intermediate-analog binding by
      ribulosebisphosphate carboxylase/oxygenase in the absence of its small subunits.
AB  - Even though depleted of more than 90% of its small subunits, ribulose 1,5
      bisphosphate carboxylase/oxygenase from Synechococcus ACMM 323 still formed a
      stable complex with 2-carboxyarabinitol 1,5-bisphosphate from which exchange of
      the activator CO(2) molecule was prevented. The stoichiometry between
      nonexchangeable CO(2) and large subunits was unchanged regardless of the presence
      or absence of small subunits. The small-subunit-depleted enzyme was also
      "activated" by exposure to CO(2) and Mg(2+), although it was necessary for the
      small subunits to be bound before this "activation" could be expressed. Binding
      of small subunits occurred rapidly, its rate depending on subunit concentration.
      The initial rate of "activation" was not slowed in the absence of small subunits
      but its extent at equilibrium was reduced. These observations are not consistent
      with an obligate role for the small subunits in the activation process. Their
      necessity in catalysis must stem from a more subtle involvement in the catalytic
      mechanism itself.

PMID- 16593474
TI  - NMR study of chloride ion interactions with thylakoid membranes.
AB  - The role of Cl(-) in photosynthetic O(2) evolution has been investigated by
      observing the (35)Cl NMR linewidth under a variety of conditions in aqueous
      suspensions of chloroplasts, primarily for the halophytes Avicennia germinans,
      Avicennia marina, and Aster tripolium but also for spinach. The line broadening
      shows there is weak, ionic binding of Cl(-) to thylakoids, the bound Cl(-)
      exchanging rapidly (>>10(4) sec(-1)) with free Cl(-) in solution. The binding is
      necessary for O(2) evolution to occur. Michaelis-Menten constants obtained from
      the Cl(-) dependence of the O(2) evolution rate are approximately 15-70 mM for
      the halophytes compared with 0.6 mM for spinach (0.5 mM with Br(-)). There appear
      to be two types of Cl(-) binding sites in halophytes, of which the stronger is
      the activator, at lower [Cl(-)], of O(2) evolution. The (35)Cl line broadening
      includes a nonspecific interaction, which becomes apparent at high Cl(-)
      concentrations (>/=0.5 M).

PMID- 16593475
TI  - Wound signals in plants: A systemic plant wound signal alters plasma membrane
      integrity.
AB  - Within 4 hr after wounding the lower leaves of young potato and tomato plants, a
      rapid and remarkable change is induced in the cells of upper undamaged leaves
      that results in extensive lysis of protoplasts during their isolation. Protoplast
      yields from unwounded upper leaves, 4 hr after wounding a lower leaf by crushing
      with a hemostat, decreased 25% below yields from leaves of unwounded plants. From
      8 to >20 hr after wounding, protoplast yields were less than half of those from
      control plants. Multiple woundings decreased yields even further, as did chewing
      of the lower leaves by tobacco hornworms over a period of several minutes. In
      addition, within 4 hr of excising young tomato plants at their base with a razor
      blade, a 90% decrease in leaf protoplast yields was recorded. The major loss of
      protoplasts induced by wounding was primarily due to an increased cell lysis
      during protoplast isolation. Cell lysis was apparently due to a weakened cell
      membrane, because newly recovered protoplasts released from leaves of wounded
      plants were extremely fragile and exhibited 70% lysis during low speed
      centrifugation, compared to 20% lysis of protoplasts recovered from control
      plants. We conclude that a signal is released by wounding that is rapidly
      transmitted or transported through the plants to induce a profound change in the
      leaf cell membranes that renders them fragile during protoplast isolation. It is
      proposed that this signal may play a role in inducing cellular changes in the
      plant cells as part of their responses to environmental stress such as pest
      attacks.

PMID- 16593476
TI  - Indole-3-acetic acid sensitization of phytochrome-controlled growth of coleoptile
      sections.
AB  - Addition of 6 muM indole-3-acetic acid (IAA) to incubation buffer increases the
      sensitivity of coleoptile sections cut from dark-grown Avena sativa L. cv. Lodi
      to red light by a factor of 10,000, relative to the response in the absence of
      added IAA, without changing the maximum amount of light-induced growth. From 0.03
      to 4 muM IAA sections show at least a 100-fold increase in sensitivity to red
      light relative to the response in the absence of added IAA. In this IAA
      concentration range, the light-induced increase in elongation shows two phases of
      response to red-light fluence, which are separated by a plateau. The biphasic
      fluence-response curve is also characteristic of the red-light-induced
      stimulation of coleoptile growth in intact dark-grown seedlings. The effect of
      IAA on the sensitivity of the phytochrome-mediated growth response appears to be
      on some step in the transduction of the phytochrome signal, rather than on the
      growth response itself.

PMID- 16593477
TI  - Neophobia in the foraging-site selection of a neotropical migrant bird: An
      experimental study.
AB  - I hand-raised chestnut-sided warblers (Dendroica pensylvanica) in a room with
      eight experimental microhabitats; the microhabitats were removed after 6 weeks. I
      then measured the response of the warblers to the eight "natal" and eight "novel"
      microhabitats in two experiments conducted 2 and 4 months after removal. Chestnut
      sided warblers responded with decreased feeding latency (neophobia) and a greater
      preference for foraging at the natal microhabitats. I suggest that an ontogenetic
      increase in neophobia restricts chestnut-sided warblers to foraging at
      microhabitats most similar to those experienced as juveniles.

PMID- 16593478
TI  - Cloning of the bronze locus in maize by a simple and generalizable procedure
      using the transposable controlling element Activator (Ac).
AB  - The bronze (bz) locus of maize has been cloned by an indirect procedure utilizing
      the cloned transposable controlling element Activator (Ac). Restriction
      endonuclease fragments of maize DNA were cloned in bacteriophage lambda and
      recombinant phage with homology to the center of the Ac element were isolated.
      The cloned fragments were analyzed to determine which contained sequences that
      were structurally identical to a previously isolated Ac element. Two such
      fragments were identified. Sequences flanking the Ac element were subcloned and
      used to probe genomic DNA from plants with well-defined mutations at the bz
      locus. By this means, it was established that one of the genomic clones contained
      a bz locus sequence. The subcloned probe fragment was then used to clone a
      nonmutant Bz allele of the locus. The method described here should prove useful
      in cloning other loci with Ac insertion mutations.

PMID- 16593479
TI  - Artificial selection for a secondary sexual character in males of Drosophila
      silvestris from Hawaii.
AB  - Drosophila silvestris is endemic to the rain forests of Hawaii Island. In
      populations from the northeast side, the male foreleg tibia bears about 100 long
      cilia; these are used as a brush to stimulate the female during courtship.
      Cyclical family selection for high and low cilia number was carried out on
      progeny of lines started from single wild isofemales collected at a single site.
      Significant response in both directions was obtained; in the third generation the
      lines differed by a mean of 25 cilia. Despite much effort to save them, both
      lines died out without further advance; the low cilia number line died after five
      and the high cilia number line died after nine generations. The data are
      compatible with the view that the cilia character is polygenic and is maintained
      in nature by a stabilizing sexual selection that also favors a polygenic
      heterozygous state. Although selection in these experiments resulted in
      dysgenesis, such a result is not inevitable. Disorganization and reorganization
      of such a genetic system following a population bottleneck might be important as
      a predisposing condition for the emergence of a specifically novel and possibly
      isolating mode of courtship.

PMID- 16593480
TI  - Chaotic motion of a weakly nonlinear, modulated oscillator.
AB  - A weakly nonlinear oscillator of natural frequency omega(0) and damping ratio
      delta is driven by an amplitude-modulated force of dimensionless amplitude
      epsilon, carrier frequency omega, and modulation frequency omega(1). Each of
      (omega - omega(0))/omega(0), omega(1)/omega(0), and delta is O(epsilon(2/3)) as
      epsilon --> 0. The response in this resonant neighborhood is a slowly modulated
      sine wave, the envelope of which is described by three first-order, autonomous,
      ordinary differential equations. This envelope, which is periodic for delta >>
      epsilon(2/3), is chaotic in certain ranges of (omega - omega(0))/omega(0) and
      omega(1)/omega(0) if delta/epsilon(2/3) is sufficiently small.

PMID- 16593481
TI  - L and epsilon functions for GSp(4) x GL(2).
AB  - The construction of L functions for automorphic cuspidal representations of
      GSp(4, A) x GL(2, A) with a Whittaker model has been given by Novodvorsky
      [Novodvorsky, M. (1979) Proc. Symp. Pure Math. 33 (2), 87-95]. In this paper, we
      prove that this L function has nontrivial poles if and only if the representation
      of GSp(4, A) is a lifting from split O(4). We also introduce a different
      construction of L functions for GSp(4) x GL(2) that is applicable to
      representations that do not have a Whittaker model-for instance, those that
      correspond to holomorphic modular forms. This construction is based on the
      lifting of these automorphic forms to Sp(4). Lifted forms will have a Whittaker
      model. This allows us to write integral expressions yielding these L functions.

PMID- 16593482
TI  - Cloning and structure determination of cDNA for cutinase, an enzyme involved in
      fungal penetration of plants.
AB  - The primary structure of cutinase, an extracellular fungal enzyme involved in the
      penetration of plants by pathogenic fungi, has been determined from the
      nucleotide sequence of cloned cDNA. Clones containing cDNA made from poly(A)(+)
      RNA isolated from fungal cultures induced to synthesize cutinase were screened
      for their ability to hybridize with the [(32)P]cDNA for mRNA unique to the
      induced culture. The 75 cDNA clones thus identified were screened for the
      cutinase genetic code by hybrid-selected translation and examination of products
      with anti-cutinase IgG. This method yielded 15 clones containing cDNA for
      cutinase, and Southern blots showed that the size of the cDNA inserts ranged from
      279 to 950 nucleotides. Blot analysis showed that cutinase mRNA contained 1050
      nucleotides, indicating that the clone containing 950 nucleotides represented
      nearly the entire mRNA. This near-full-length cDNA and the restriction fragments
      subcloned from it were sequenced by a combination of the Maxam-Gilbert and the
      phage M13-dideoxy techniques. cDNAs from two other clones, containing the bulk of
      the coding region for cutinase, were also completely sequenced, and the results
      confirmed the sequence obtained with the first clone. A peptide isolated from a
      trypsin digest of cutinase was sequenced and the amino acid sequence as well as
      the initiation and termination codons were used to identify the coding region of
      the cDNA. The primary structure of the enzyme so far determined by amino acid
      sequencing ( approximately 40% of the total) agreed completely with the
      nucleotide sequencing results. Thus, the complete primary structure of the mature
      enzyme and that of the signal peptide region were ascertained.

PMID- 16593483
TI  - Membrane protein damage and repair: Selective loss of a quinone-protein function
      in chloroplast membranes.
AB  - A loss of electron transport capacity in chloroplast membranes was induced by
      high-light intensities (photoinhibition). The primary site of inhibition was at
      the reducing side of photosystem II (PSII) with little damage to the oxidizing
      side or to the reaction center core of PSII. Addition of herbicides (atrazine or
      diuron) partially protected the membrane from photoinhibition; these compounds
      displace the bound plastoquinone (designated as Q(B)), which functions as the
      secondary electron acceptor on the reducing side of PSII. Loss of function of the
      32-kilodalton Q(B) apoprotein was demonstrated by a loss of binding sites for
      [(14)C]atrazine. We suggest that quinone anions, which may interact with
      molecular oxygen to produce an oxygen radical, selectively damage the apoprotein
      of the secondary acceptor of PSII, thus rendering it inactive and thereby
      blocking photosynthetic electron flow under conditions of high photon flux
      densities.

PMID- 16593484
TI  - Isolation and characterization of a gene for a major light-harvesting polypeptide
      from Cyanophora paradoxa.
AB  - Antibodies raised against mixtures of phycobilisome polypeptides from the
      eukaryotic alga Cyanidium caldarium were used in an immunological screen to
      detect expression of phycobiliprotein genes in an Escherichia coli library
      containing segments of plastid (chloroplast, cyanelle) DNA from another
      eukaryotic alga, Cyanophora paradoxa. The four candidate clones obtained were
      mapped by restriction analysis and found to be overlapping. The clone with the
      smallest insert (1.4 kilobases) was partially sequenced and a coding region
      similar to the carboxyl terminus of the phycobiliprotein subunit beta-phycocyanin
      was found. The coding region for the beta-phycocyanin gene in C. paradoxa has
      been mapped to the small single copy region on the cyanelle genome, and its
      orientation has been determined. A short probe unique to a conserved chromophore
      binding site shared by at least two phycobiliprotein subunits has now been
      generated from the carboxyl terminus of the beta-phycocyanin gene. This probe may
      be useful in identifying specific phycobiliprotein subunit genes, beta
      phycocyanin, beta-phycoerythrocyanin, and possibly beta-phycoerythrin, in other
      eukaryotic algae and in prokaryotic cyanobacteria.

PMID- 16593485
TI  - Cleavage of single-stranded DNA by the varphiX174 A protein: The A-single
      stranded DNA covalent linkage.
AB  - Phage varphiX174 A(*) protein cleaves single-stranded DNA and then binds to the
      5'-phosphorylated terminus of the cleaved DNA fragment, forming a covalent
      protein-DNA complex. The bound A(*) protein can religate the termini to form
      covalently closed single-stranded circles. To determine the nature of the
      covalent linkage and the amino acid involved, we used A(*) protein to cleave DNA
      synthesized in vivo with [alpha-(32)P]dATP to form the A(*)-single-stranded DNA
      complex. The complex was then digested with DNase I and the (32)P-labeled A(*)
      protein was isolated by electrophoresis on polyacrylamide gels. The isolated
      complex was digested with either trypsin or Pronase. Incubation of the tryptic
      digest with snake venom phosphodiesterase gave (32)P-labeled products that
      migrated on electrophoresis on cellulose plates to the cathode, indicating
      covalent linkage of (32)P-labeled dAMP residues to a tryptic peptide. High
      concentrations of snake venom phosphodiesterase released all of the (32)P label
      as free dAMP. Formic acid/diphenylamine depurination (Burton reaction) of the
      [alpha-(32)P]dATP-labeled peptide-oligonucleotide complexes caused a transfer of
      the labeled phosphate from dAMP to the peptide. The phosphorylated peptides were
      isolated on cellulose plates and shown to be sensitive to bacterial alkaline
      phosphatase, indicating that a phosphodiester bond linked the peptides to the
      dAMP. The phosphorylated product of the Pronase digest was identified as free
      phosphotyrosine by its mobility in three different chromatography systems.
      Likewise, acid hydrolysis (5.6 M HCl, 110 degrees C, 2 hr) of the phosphorylated
      tryptic peptides revealed linkage of the phosphate to a tyrosine. Thus, A(*)
      protein cleaves single-stranded DNA and binds covalently to the 5'-phosphorylated
      terminus via a tyrosyl-dAMP phosphodiester bond.

PMID- 16593486
TI  - An Escherichia coli mutant deficient in pyruvate oxidase activity due to altered
      phospholipid activation of the enzyme.
AB  - The pyruvate oxidase (pyruvate:ferricytochrome b(1) oxidoreductase, EC 1.2.2.2)
      of Escherichia coli is markedly activated by phospholipids in vitro. To test the
      physiological relevance of this activation, we isolated an E. coli mutant
      producing an oxidase that is deficient in activation by (and binding to)
      phospholipids. The mutant oxidase could be fully activated by a specific
      proteolytic cleavage, indicating that the catalytic site is normal. The mutant
      enzyme functions poorly in vivo, indicating that activation of the oxidase by
      phospholipids plays an important physiological role.

PMID- 16593487
TI  - Soliton-assisted unidirectional circulation in a biochemical cycle.
AB  - The unidirectional circulation of an enzyme round a working cycle can be
      understood in terms of the formation and decay of a soliton that acts as a ligand
      for the protein and for which the surrounding heat bath serves as a sink. An
      experimental confirmation of this interpretation is suggested in which the
      soliton is of the Davidov type and is created by infrared photon absorption as in
      recent experiments on acetanilide.

PMID- 16593488
TI  - Transitions between oscillatory modes in a glycolytic model system.
AB  - A glycolytic model system consisting of the enzymes phosphofructokinase (EC
      2.7.1.11) and pyruvate kinase (EC 2.7.1.40) is analyzed when subject to periodic
      substrate addition. The calculations are performed by using detailed rate laws
      that have been derived for the enzymes of Escherichia coli. Due to linear
      relationships between the metabolite concentrations, the numerical solutions can
      be displayed inside a trapezium, so that the concentrations of four different
      metabolites are indicated along the trapezium edges. The analysis reveals a rich
      variety of time patterns, corresponding to different periodic, quasiperiodic, and
      chaotic attractors. These patterns undergo complex hysteresis loops when
      bifurcation parameters are slowly changed-for example, by modulating the input
      amplitude. By using this technique up to four attractors coexisting in phase
      space are found. The time patterns corresponding to coexisting attractors can be
      switched into one another by triggering the system with short substrate pulses.
      Furthermore, conditions exist at which the triggering is autonomous-i.e., self
      sustained (intermittent) switchings occur. The time between these switchings can
      be set externally by the value of the input amplitude. For conditions in which
      the periods of the oscillations are in the order of minutes, the self-sustained
      switching-which modulates these oscillations-can be in the order of hours.

PMID- 16593489
TI  - Optimal conditions for cell-free synthesis of citrus exocortis viroid and the
      question of specificity of RNA polymerase activity.
AB  - Cell-free synthesis of citrus exocortis viroid (CEV) in nuclei-rich preparations
      from infected Gynura aurantiaca was optimum at 18-24 degrees C. Incubation of
      reaction mixtures at higher temperatures (30-36 degrees C) resulted in an
      increase of CEV linear molecules and the recovery of incomplete or nicked newly
      synthesized RNA species. Although the Mg(2+) optimum (2.5-5 mM) for CEV synthesis
      was lower than that for total [(32)P]CMP incorporation (10 mM), the response to
      Mn(2+) ion was distinctly different. Whereas maximum total activity was observed
      in 1 mM Mn(2+) with a pronounced reduction (80%) in 5 mM Mn(2+), CEV synthesis
      was maintained in 1-15 mM Mn(2+). Inhibition of alpha-amanitin-sensitive CEV
      synthesis in 200 mM (NH(4))(2)SO(4) resembles the reaction of RNA polymerase II
      on a free nucleic acid template. However, detection of trace levels of alpha
      amanitin-resistant CEV synthesis activity inhibited by low (NH(4))(2)SO(4)
      concentrations (25 mM) suggests the possible involvement of RNA polymerase I-
      and/or III-like activity.

PMID- 16593490
TI  - Fossil vertebrates from Antigua, Lesser Antilles: Evidence for late Holocene
      human-caused extinctions in the West Indies.
AB  - Vertebrate remains recovered from a limestone fissure filling on Antigua, Lesser
      Antilles, are associated with radiocarbon dates ranging from 4300 to 2500 yr
      B.P., contemporaneous with the earliest aboriginal human occupation of the
      island. Nine taxa of lizards, snakes, birds, bats, and rodents (one-third of the
      total number of species represented as fossils) are either completely extinct or
      have never been recorded historically from Antigua. These extinctions came long
      after any major climatic changes of the Pleistocene and are best attributed to
      human-caused environmental degradation in the past 3500 yr. Such unnatural
      influences have probably altered patterns of distribution and species diversity
      throughout the West Indies, thus rendering unreliable the data traditionally used
      in ecological and biogeographic studies that consider only the historically known
      fauna.

PMID- 16593491
TI  - Portage of various compounds into bacteria by attachment to glycine residues in
      peptides.
AB  - Synthetic di- and oligopeptides are described that contain nucleophilic moieties
      attached to the alpha carbon of a glycine residue. These peptides are accepted by
      the peptide transport systems of Escherichia coli (and other microorganisms) and
      are capable of being hydrolyzed by intracellular peptidases. After liberation of
      its amino group the alpha-substituted glycine is chemically unstable (although it
      is stable in peptide form) and decomposes, releasing the nucleophilic moiety.
      Thus, the combined result of peptide transport and peptidase action is the
      intracellular release of the nucleophile. Peptides containing glycine residues
      alpha-substituted with thiophenol, aniline, or phenol are used as models for this
      type of peptide-assisted entry and their metabolism by E. coli is described.
      Peptides of this type have broad applicability to the study of microbial
      physiology and the development of an additional class of antimicrobial agents.

PMID- 16593492
TI  - Statistical thermodynamics of amphiphile chains in micelles.
AB  - The probability distribution of amphiphile chain conformations in micelles of
      different geometries is derived through maximization of their packing entropy. A
      lattice model, first suggested by Dill and Flory, is used to represent the
      possible chain conformations in the micellar core. The polar heads of the chains
      are assumed to be anchored to the micellar surface, with the other chain segments
      occupying all lattice sites in the interior of the micelle. This "volume-filling"
      requirement, the connectivity of the chains, and the geometry of the micelle
      define constraints on the possible probability distributions of chain
      conformations. The actual distribution is derived by maximizing the chain's
      entropy subject to these constraints; "reversals" of the chains back towards the
      micellar surface are explicitly included. Results are presented for amphiphiles
      organized in planar bilayers and in cylindrical and spherical micelles of
      different sizes. It is found that, for all three geometries, the bond order
      parameters decrease as a function of the bond distance from the polar head, in
      accordance with recent experimental data. The entropy differences associated with
      geometrical changes are shown to be significant, suggesting thereby the need to
      include curvature (environmental)-dependent "tail" contributions in statistical
      thermodynamic treatments of micellization.

PMID- 16593493
TI  - The spectral domain of multivariate harmonizable processes.
AB  - The spectral or frequency domain of a multivariate weakly harmonizable process is
      a vector space of vector functions that are integrable relative to a positive
      definite matrix bimeasure. It has a norm derived from a Gramian inner product.
      The completeness property of this space, which is needed for many applications,
      has been open for some years. An affirmative solution and an application to
      optimal least-squares estimation of a weakly harmonizable signal are presented
      here.

PMID- 16593494
TI  - Geodesic flow on SO(4) and the intersection of quadrics.
AB  - This note studies the relationship between the complete integrability of geodesic
      flow on SO(4) with a left-invariant metric and the geometry of the intersection
      of four quadrics in P(6).

PMID- 16593495
TI  - Identification of a cloned cytokinin biosynthetic gene.
AB  - A small region of the Ti plasmid (the tmr locus), thought to be involved in
      phytohormone metabolism in Agrobacterium tumefaciens-transformed plant tissue,
      was cloned and expressed in Escherichia coli. By enzyme assay, the tmr locus was
      shown to encode isopentenyltransferase, an enzyme that catalyzes the first step
      in cytokinin biosynthesis.

PMID- 16593496
TI  - Isoelectric focusing of plant cell membranes.
AB  - An isoelectric focusing method is described that discriminates plant cell
      organelle populations on the basis of surface charge. The isoelectric points (pI
      values) of the Golgi apparatus, the mitochondria, and putative plasma membrane
      from etiolated pea stem cells are reported. The pI of the pea Golgi apparatus is
      similar to that of the (35)SO(4)-labeled membranes of developing Fucus embryos.
      The pI of Fucus(35)SO(4)-labeled membranes depends on whether the membranes are
      being polarly transported to the growing tip or randomly transported to the
      entire periphery of the zygote. Those subject to polar tip transport have a
      significantly greater negative surface charge than those being randomly
      transported. The implication of this result toward an understanding of the
      localization mechanism is discussed. The method is also capable of
      subfractionating glucan synthetase II-containing membranes (putative plasma
      membrane) from peas. The pI of putative plasma membrane from a pea stem
      homogenate is similar to the pI of the plasma membrane of whole protoplasts of
      Catharanthus leaf cells. Isoelectric focusing appears to be a useful technique to
      discriminate membranes and, hence, to provide new information and approaches to
      study cellular and developmental phenomena.

PMID- 16593497
TI  - Maturation of catalase precursor proceeds to a different extent in glyoxysomes
      and leaf peroxisomes of pumpkin cotyledons.
AB  - As an approach to study the mechanism of the microbody transition (glyoxysomes to
      leaf peroxisomes) in greening pumpkin cotyledons, catalase molecules were
      purified from the two different types of microbody and their structural
      properties were compared. The purified glyoxysomal catalase was found to consist
      of four identical subunits (55 kDa), whereas the leaf peroxisomal catalase
      contains two different forms of monomeric subunit (55 and 59 kDa). These
      different catalase species cross-reacted with the rabbit antibody raised against
      the glyoxysomal enzyme. During gel filtration on an Ultrogel AcA 34 column, the
      leaf peroxisomal 55-kDa polypeptide eluted slightly faster than the leaf
      peroxisomal 59-kDa polypeptide. The profile of catalase activities exactly
      paralleled the elution pattern of the 55-kDa molecules, which indicated that the
      59-kDa polypeptide was enzymically inactive. Peptide mapping analysis using
      Staphylococcus aureus protease V8 showed that the glyoxysomal 55-kDa polypeptide
      was identical to the leaf peroxisomal 55-kDa species, whereas the leaf
      peroxisomal 59-kDa polypeptide had a different primary structure from the 55-kDa
      polypeptide. In an in vitro translation system directed by mRNA isolated from
      etiolated and green cotyledons, glyoxysomal and leaf peroxisomal catalases were
      synthesized as the identical 59-kDa polypeptide. From peptide mapping analysis,
      the in vitro-translated 59-kDa polypeptide was found to have a nearly identical
      primary structure to that of the leaf peroxisomal 59-kDa species. In vivo pulse
      chase labeling experiments using etiolated cotyledons showed the conversion of
      the 59-kDa polypeptide to the 55-kDa molecular species. The overall results
      strongly indicate that the 59-kDa polypeptide is a precursor form of catalase in
      pumpkin cotyledons.

PMID- 16593498
TI  - Guatemalan forest synthesis after Pleistocene aridity.
AB  - Sediments from two lakes in the Peten Department, Guatemala, provide
      palynological evidence from Central America of late Pleistocene aridity and
      subsequent synthesis of mesic forests. Late Glacial vegetation consisted of
      marsh, savanna, and juniper scrub. An early Holocene temperate forest preceded a
      mesic tropical forest with Brosimum (ramon). Thus "primeval" rain forests of
      Guatemala are no older than 10,000 to 11,000 years and are considerably younger
      in the Peten due to Mayan disturbances. Among dated Neotropical sites, the Peten
      has the most mesic vegetation yet shown to have supplanted xeric vegetation
      present during the Pleistocene. The arid late Glacial-humid early Holocene
      transition appears to have been pantropical in the lowlands. The Peten was not a
      Pleistocene refugium for mesophytic taxa, as has been suggested. Thus genesis of
      extant rain forests in northern Central America and southern Mexico remains
      unexplained.

PMID- 16593499
TI  - Eutherian-like reproductive specializations in a viviparous reptile.
AB  - The viviparous Brazilian scincid lizard Mabuya heathi exhibits a suite of
      reproductive specializations widely believed to be confined to the eutherian
      mammals. This skink ovulates the smallest known reptilian egg ( approximately 1.0
      mm in diameter). Placental transport accounts for >99% of the dry mass of the
      periparturient fetus, representing a degree of placentotrophy proportionately
      greater than that reported in any other non-mammalian vertebrate. Placental
      morphology and the timing of fetal growth implicate the chorioallantoic placenta
      in maternal-fetal nutrient transfer. The yolk sac placenta regresses prior to any
      major increase in embryonic dry mass. Precocial gonadal maturation and
      postponement of reproductive investment until well after ovulation enables
      females to become pregnant at 3-4 months of age, long before attainment of full
      adult body size.

PMID- 16593500
TI  - Regulation of pea seed pyrophosphate-dependent phosphofructokinase: Evidence for
      interconversion of two molecular forms as a glycolytic regulatory mechanism.
AB  - Two molecular forms of pyrophosphate-dependent phosphofructokinase (PP(i)-PFK;
      pyrophosphate:D-fructose-6-phosphate 1-phosphotransferase; EC 2.7.1.90) have been
      found whose activity depends upon association and dissociation characteristics
      regulated by fructose 2,6-bisphosphate (Fru-2,6-P(2)). PP(i)-PFK was purified 200
      fold from cotyledons of germinating pea seeds and found to exist in two
      interconvertible molecular forms. The two forms of PP(i)-PFK have sedimentation
      coefficients of 6.3 and 12.7 S during ultracentrifugation in sucrose density
      gradients and also differ both in sensitivity to the activator Fru-2,6-P(2) and
      in affinity for the substrate fructose 6-phosphate. The major component of enzyme
      activity is in the large form (12.7 S), but the small, less-active, form (6.3 S)
      predominates when the enzyme preparation is extracted and stored in buffer
      without Fru-2,6-P(2) and glycerol. Urea (1 M) or pyrophosphate (20 mM) treatment
      results in at least a 50% loss of activity in the glycolytic direction, whereas
      these treatments had much less influence on the gluconeogenic direction activity.
      Concomitant with the loss of glycolytic activity the enzyme dissociates into the
      small form. Fru-2,6-P(2) stabilizes the large form of the enzyme against the
      dissociating effects of pyrophosphate and prevents the inactivation in the
      glycolytic direction during either urea or pyrophosphate treatment. The small
      molecular form of the enzyme is converted into the large form in the presence of
      Fru-2,6-P(2). We propose that glycolytic and gluconeogenic hexose metabolism in
      plants includes a regulatory mechanism induced by Fru-2,6-P(2) that involves the
      interconversion of two molecular forms of PP(i)-PFK.

PMID- 16593501
TI  - Different evolutionary behavior of structurally related, repetitive sequences
      occurring in the same Balbiani ring gene in Chironomus tentans.
AB  - The Balbiani ring 2 (BR 2) gene in Chironomus tentans is highly internally
      repeated. Two types of related repeat units-the alpha and beta types-are tandemly
      arranged in separate blocks, which together are likely to form the major part of
      the gene. Every repeat unit has one constant region and one subrepeat region.
      Here we analyze the length and sequence of a number of repeat units of both types
      and compare the units within and between the blocks. The approximately 100 alpha
      repeat units are essentially invariant regarding length and sequence. In
      contrast, when the approximately 70 beta repeat units are compared, six length
      variants are found, four of which have been sequenced. The length variations
      reside in the subrepeat regions and are due to different numbers of whole or half
      subrepeats. Furthermore, the subrepeat regions differ by several base-pair
      substitutions, many of which change the amino acid sequence. On the other hand,
      all beta-type constant regions are of equal length and are virtually homogeneous
      in sequence. The observed length distributions in combination with analysis of
      the basepair substitutions in the alpha-and beta-type constant and subrepeat
      regions suggest that the alpha and beta blocks are of different age, that
      seemingly homologous repeated regions may play different functional roles at the
      protein level, and that sequence correction mechanisms are likely to operate to
      different extents on the constant and subrepeat regions within the beta block.

PMID- 16593502
TI  - Estimation of mating system parameters when outcrossing events are correlated.
AB  - Many plant species have mating systems characterized by a mixture of self
      fertilization and outcrossing. Statistical estimation of the outcrossing rate has
      relied on a model of the mating process that assumes that successive outcross
      events within a family arise from independent draws of pollen from the total
      population of male plants. Although this assumption is likely to be most
      appropriate for wind-pollinated plants, it is not appropriate in certain insect
      pollinated plants. An alternative model is developed that assumes that successive
      outcross events within a family involve pollen drawn from a single male parent.
      The estimation of the parameters that index this model is outlined and a
      procedure for calculating the variances of the parameter estimates is presented.
      Monte Carlo simulations of the sampling processes assumed by each model are also
      presented. The simulations show that application of the incorrect estimation
      model to data can lead to a large bias in parameter estimates.

PMID- 16593503
TI  - On stabilization of the solutions of parabolic equations with small parameter.
AB  - We consider two classes of quasi-linear parabolic equations depending on a small
      parameter epsilon. The asymptotic behavior of the solutions as t --> alpha and
      epsilon --> 0 is investigated by studying the associated Markov family. We find
      its dependence on the way t and epsilon(-1) go to infinity and on the initial
      point.

PMID- 16593504
TI  - The restricted simple Lie algebras are of classical or Cartan type.
AB  - The classification of the finite-dimensional restricted simple Lie algebras over
      an algebraically closed field F of prime characteristic p > 7 is announced. Such
      an algebra is either of classical type (an analogue over F of a finite
      dimensional simple Lie algebra over the complex numbers) or of Cartan type (an
      analogue over F of one of the infinite Lie algebras of Cartan over the complex
      numbers).

PMID- 16593505
TI  - On finite subgroups of SU(2), simple Lie algebras, and the McKay correspondence.
AB  - The question is considered of how the restriction pi(n)Gamma, where pi(n) is
      irreducible for all n and Gamma is a finite subgroup of SU(2), decomposes into
      Gamma-irreducibles for any arbitrary n in [unk](+). It is announced that, using
      the McKay correspondence, the problem has an elegant solution in terms of the
      Coxeter element for the associated Lie algebra and that the numbers involved come
      in a beautiful way from the root structure.

PMID- 16593506
TI  - Post-classification version of Jordan's theorem on finite linear groups.
AB  - Using classification of finite simple groups, I show that a finite subgroup G of
      GL(n)(C), where C = the complex numbers, contains a commutative normal subgroup M
      of index at most (n + 1)!n(alogn+b). Moreover, if G is primitive and does not
      contain normal subgroups that are direct products of large alternating groups,
      then the factor (n + 1)! can be dropped. I further show that similar statements
      hold also in characteristics p >/= 2, if one takes M to be an extension of a
      group of Lie type of characteristic p by a solvable group that has a normal p
      subgroup with commutative p'-quotient. These results improve the celebrated
      theorems of Jordan and of Brauer and Feit.

PMID- 16593507
TI  - Transfer of nuclei from a parasite to its host.
AB  - During the normal course of infection, nuclei are transferred via secondary pit
      connections from the parasitic marine red alga Choreocolax to its red algal host
      Polysiphonia. These "planetic" nuclei are transmitted by being cut off into
      specialized cells (conjunctor cells) that fuse with an adjacent host cell,
      thereby delivering parasite nuclei and other cytoplasmic organelles into host
      cell cytoplasm. Within the foreign cytoplasm, planetic nuclei survive for several
      weeks and may be active in directing the host cellular responses to infection,
      since these responses are seen only in host cells containing planetic nuclei. The
      transfer and long-term survival of a nucleus from one genus into the cytoplasm of
      another through mechanisms that have evolved in nature challenge our
      understanding of nuclear-cytoplasmic interactions and our concept of
      "individual."

PMID- 16593508
TI  - Dimethyl sulfoxide can initiate cell divisions of arrested callus protoplasts by
      promoting cortical microtubule assembly.
AB  - A serious problem in the technology of plant cell culture is that isolated
      protoplasts from many species are reluctant to divide. We have succeeded in
      inducing consecutive divisions in a "naturally" arrested system-i.e., protoplasts
      from a hibiscus cell line, which do not divide under standard conditions-and in
      an artificially arrested system-i.e., colchicine-inhibited callus protoplasts of
      Nicotiana glutinosa, which do readily divide in the absence of colchicine. In
      both cases, the reinstallation of a net of cortical microtubules, which had been
      affected either by colchicine or by the protoplast isolation procedure, resulted
      in continuous divisions of the formerly arrested protoplasts. Several compounds
      known to support microtubule assembly in vitro were tested for their ability to
      promote microtubule assembly in vivo. Best results were obtained by addition of
      dimethyl sulfoxide to the culture medium. Unlimited amounts of callus could be
      produced with the dimethyl sulfoxide method from protoplasts which never
      developed a single callus in control experiments.

PMID- 16593509
TI  - Water flow and coral colony size: Interhabitat comparisons of the octocoral
      Alcyonium siderium.
AB  - Colonies of the octocoral Alcyonium siderium Verrill form aggregations on
      subtidal vertical rock walls in the Gulf of Maine. Maximum and mean colony sizes
      increase dramatically from protected embayments to sites exposed to ocean swells
      and from the bottom to the top of each vertical wall studied. Water movement
      along the substratum, generated by surface waves and tides, also increases along
      both gradients. Although plankton concentrations were similar at all sites during
      a 2-yr period, increased encounter rates of zooplankton with coral tentacles will
      result in greater energy intake and, thus, faster growth rates at the more
      exposed sites with greater flow. Other hypotheses for the proximate cause of the
      size gradient, such as differential mortality of large colonies or generally
      higher mortality rates at the protected site, are not consistent with available
      data.

PMID- 16593510
TI  - Repeatability of taxon longevity in successive foraminifera radiations and a
      theory of random appearance and extinction.
AB  - An analysis of taxonomic longevity for species of the two Cenozoic radiations of
      Caribbean planktonic foraminifera shows strong similarity in longevity for
      extinct taxa, though extant species of the latter radiation are biased towards
      longer-lived forms. In this case, the present is not the key to the past. A
      simple one-parametric stochastic model predicts generally the shape of the
      distributions, though there is an excess of species with model longevity and a
      deficiency of longer-lived forms, relative to the prediction of the model.
      Although the one parameter may relate to the biology of the group under
      consideration, the distribution about the mode may reflect random appearance
      extinction processes.

PMID- 16593511
TI  - "Hopeful monsters," transposons, and Metazoan radiation.
AB  - The appearance of many novel morphologies, frequently expressed taxonomically as
      new phyla, classes, or orders, occurs with such rapidity in evolutionary time
      that microevolutionary substitutions involving structural genes seem an
      implausible mechanism. It has been suggested that such novelties are produced by
      changes in developmental and regulatory structures and patterns rather than by an
      accumulation of single structural gene changes. The horizontal transmission of
      genetic material via RNA-based viruses between members of a population may
      rapidly create intrafertile sub-populations that differ markedly from their
      parents and form the basis of new morphological types, avoiding the usual fitness
      problems associated with "hopeful monsters."

PMID- 16593512
TI  - Evidence for the presence of makisterone A in Drosophila larvae and the secretion
      of 20-deoxymakisterone A by the ring gland.
AB  - Ring glands or brain-ring gland complexes from third-instar Drosophila
      melanogaster larvae secreted ecdysone [(22R)-2beta,3beta,14alpha,22,25
      pentahydroxy-5beta-cholest-7-en-6-one] and two less polar ecdysteroids (LP1 and
      LP2) in vitro. Radioimmunoassay with different antisera indicated that LP1 and
      LP2 are side-chain-modified analogues of ecdysone. In high-performance liquid
      chromatography, the retention time of LP2 was equivalent to that of a precursor
      of makisterone A [(20R,22R)-2beta,3beta,14alpha,20,22,25-hexahydroxy-24-methyl
      5beta-cholest-7-en-6-one] secreted by Dysdercus fasciatus prothoracic glands in
      vitro. LP2 was metabolized in vitro by the fat body of Drosophila larvae to a
      product with the characteristics of makisterone A when analyzed by gas
      chromatography/mass spectrometry (selected ion monitoring). Evidence was obtained
      for the presence of makisterone A in Drosophila larvae. These data suggest that
      LP2 is 20-deoxymakisterone A (24-methylecdysone) and that makisterone A could
      function as an additional moulting hormone in Drosophila, although 20
      deoxymakisterone A production is apparently dependent on the sterol composition
      of the diet. LP1 has not been identified.

PMID- 16593513
TI  - Elicitor rapidly induces chalcone synthase mRNA in Phaseolus vulgaris cells at
      the onset of the phytoalexin defense response.
AB  - DNAs complementary to poly(A)(+) RNA present in elicitor-treated cells of
      Phaseolus vulgaris L. were inserted into pBR325 and used to transform Escherichia
      coli strain JA221. A clone was identified that contained sequences complementary
      to mRNA encoding chalcone synthase, a regulatory enzyme of phenylpropanoid
      biosynthesis, which catalyzes the first reaction of a branch pathway specific to
      flavonoid and isoflavonoid biosynthesis. Rapid, marked but transient increases in
      chalcone synthase mRNA in response to elicitor treatment were observed by RNA
      blot hybridization with (32)P-labeled chalcone synthase cDNA sequences. Induction
      of chalcone synthase mRNA governs the rate of enzyme synthesis throughout the
      phase of rapid increase in enzyme activity at the onset of accumulation of
      isoflavonoid-derived phytoalexins. The data are consistent with the hypothesis
      that elicitor causes a rapid transient stimulation of transcription of chalcone
      synthase gene(s) as an early event in the expression of the phytoalexin defense
      response.

PMID- 16593515
TI  - A theorem about Hamiltonian systems.
AB  - A simple theorem in Hamiltonian mechanics is pointed out. One consequence is a
      generalization of the classical result that symmetries are generated by Poisson
      brackets of conserved functionals. General applications are discussed. Special
      emphasis is given to the Kadomtsev-Petviashvili equation.

PMID- 16593514
TI  - Expression of beta-galactosidase controlled by a nitrogenase promoter in stem
      nodules of Aeschynomene scabra.
AB  - A 365-base-pair (bp) DNA fragment, containing the promoter region of the
      nitrogenase reductase (nifH) gene from stem Rhizobium BTAi1, has been isolated
      and sequenced. The transcription initiation sites were localized at positions 152
      (major initiation) and 114 (minor initiation) nucleotides upstream of the
      translation initiation codon. The 200-bp nucleotide sequence upstream of the nifH
      structural gene shows substantial homology to the corresponding nifH regions of
      cowpea Rhizobium (100%), Parasponia Rhizobium (89%), and Rhizobium japonicum
      (88%). The nifH promoter region of stem Rhizobium BTAi1 was fused to the lacZ
      gene of Escherichia coli. The fusion and a 1.6-kilobase DNA specifying neomycin
      phosphotransferase were inserted into a 3,4-kilobase fragment of stem Rhizobium
      chromosome, and the resulting construct was placed on a mobilizable vector,
      pREV1000. Stem Rhizobium transconjugants resistant to kanamycin were found to
      contain the nifH promoter region-lacZ fusion linked to the neomycin
      phosphotransferase gene at the site of chromosomal homology. Analysis of the DNA
      from stable transconjugants showed integration of a single copy of these
      sequences into the chromosome by a double-reciprocal crossover event. The
      transconjugants formed nitrogen-fixing nodules, indicating that the insertion
      occurred in a "nonessential" region of the stem Rhizobium chromosome.
      Transconjugant strain BTAi1000 grows on beta-galactosidase indicator plates under
      aerobic conditions as white colonies, whereas under microaerobic conditions (97%
      N(2)/3% O(2)), which derepress nitrogenase, the colonies turn blue within 15-24
      hr. beta-Galactosidase activity in derepressed cultures of BTAi1000 showed a 200
      fold increase in comparison to the wild-type strain, whereas stem nodules formed
      by BTAi1000 exhibited 15- to 20-fold higher beta-galactosidase values than wild
      type nodules. Nitrogenase promoter-dependent expression of beta-galactosidase in
      stem nodules was inhibited by fixed nitrogen, suggesting that the nifH promoter
      lacZ fusion is controlled coordinately in trans with the native nif region.

PMID- 16593516
TI  - Water structure of a hydrophobic protein at atomic resolution: Pentagon rings of
      water molecules in crystals of crambin.
AB  - The water structure has been analyzed for a model of the protein crambin refined
      against 0.945-A x-ray diffraction data. Crystals contain 32% solvent by volume,
      and 77% of the solvent molecules have been located-i.e., 2 ethanol molecules and
      64 water molecules with 10-14 alternate positions. Many water oxygen atoms found
      form chains between polar groups on the surface of the protein. However, a
      cluster of pentagonal arrays made up of 16 water molecules sits at a hydrophobic,
      intermolecular cleft and forms a cap around the methyl group of leucine-18.
      Several waters in the cluster are hydrogen-bonded directly to the protein.
      Additional closed circular arrays, which include both protein atoms and other
      water oxygen atoms, form next to the central cluster. This water array stretches
      in the b lattice direction between groups of three ionic side chains.

PMID- 16593517
TI  - Cloned avirulence gene of Pseudomonas syringae pv. glycinea determines race
      specific incompatibility on Glycine max (L.) Merr.
AB  - A genomic library of Pseudomonas syringae pv. glycinea race 6 DNA was constructed
      in the mobilizable cosmid vector pLAFR1 and maintained in Escherichia coli HB101.
      Completeness of the library was estimated by assaying clones for the expression
      of ice-nucleating activity in E. coli. Ice-nucleation activity was represented
      approximately once in every 600 clones. Six hundred eighty random race 6 cosmid
      clones were mobilized from E. coli by plasmid pRK2013 in individual conjugations
      to a race 5 strain of P. s. glycinea. A single clone (pPg6L3) was detected that
      changed the race specificity of race 5 from virulent (compatible) to avirulent
      (incompatible) on the appropriate soybean cultivars. The clone was also mobilized
      from E. coli into race 1 and race 4 strains of P. s. glycinea, and it conferred
      on these transconjugants the same host range incompatibility as the wild-type
      race 6 strain. The cosmid clone was mapped by restriction endonucleases, and two
      adjacent EcoRI fragments were identified by transposon Tn5 mutagenesis to be
      important in determining race specificity. Southern blot analysis showed that the
      two EcoRI fragments are unique to race 6 and are not present in the other races
      tested. The cosmid clone pPg6L3 was also mobilized to Pseudomonas fluorescens and
      Rhizobium japonicum. However, neither these isolates nor E. coli harboring pPg6L3
      elicited a hypersensitive reaction in soybean leaves.

PMID- 16593518
TI  - Biosynthesis of carbonic anhydrase in Chlamydomonas reinhardtii during adaptation
      to low CO(2).
AB  - The unicellular green alga Chlamydomonas reinhardtii synthesizes carbonic
      anhydrase in response to low levels of CO(2) (i.e., air levels of CO(2)). This
      enzyme, localized predominantly in the periplasmic space of the alga (or
      associated with the cell wall), is an important component of the machinery
      required for the active accumulation of inorganic carbon by C. reinhardtii and
      the saturation of ribulose-1,5-bisphosphate carboxylase at low extracellular
      carbon concentrations. We have begun to examine the synthesis and
      compartmentalization of carbonic anhydrase in C. reinhardtii. The monomeric
      species associated with carbonic anhydrase activity is synthesized as a precursor
      on 80S cytoplasmic ribosomes. This precursor can be detected immunologically in
      the profiles of translation products when a reticulocyte lysate, cell-free system
      is primed with poly(A)-RNA from either air-grown C. reinhardtii or cells shifted
      from growth on 5% CO(2) to air for 12 hr. It is not synthesized when the in vitro
      system is primed with poly(A)-RNA from CO(2)-grown algae. Since translatable RNA
      for the polypeptide responsible for carbonic anhydrase activity was only present
      in cells that experienced low levels of CO(2), the adaptation process either
      involves the regulation of transcription of the carbonic anhydrase gene (and
      perhaps other genes involved in adaptation) or the post-transcriptional
      processing of the messenger RNA. Furthermore, the appearance of the mature
      polypeptide associated with carbonic anhydrase activity in the periplasmic space
      of C. reinhardtii is inhibited by tunicamycin, an antibiotic that prevents core
      glycosylation of polypeptides on the endoplasmic reticulum. Together, these
      results suggest that the biosynthesis of this extracellular algal enzyme involves
      the translation of mRNA for the carbonic anhydrase monomer on ribosomes bound to
      the endoplasmic reticulum, the cleavage of a signal sequence during transport of
      the nascent polypeptide into the lumen of the endoplasmic reticulum, and
      subsequent glycosylation events prior to export across the plasmalemma.

PMID- 16593519
TI  - Electrical polarity in embryos of wild carrot precedes cotyledon differentiation.
AB  - Endogenous electrical currents traverse embryos of a higher plant, the wild
      carrot Daucus carota L. Current enters the apical pole and leaves the region near
      the presumptive radicle in the radially symmetric globular embryo. Current also
      enters the exposed surfaces of incipient globular embryos. This electrical
      polarity precedes differentiation of vascular tissue and cotyledon development.
      Localized current is observed at both growing ends of the embryos in subsequent
      stages of embryogenesis. Inward current is found at the cotyledons; outward
      current is found at the radicle/root. Exogenous indole-3-acetic acid (3 muM)
      reversibly inhibits these currents. Little current traverses the surface of
      intermediate regions of the embryo. The ionic gradients generated by these
      currents may be important in accumulation of metabolites and in other
      developmental processes within the embryo.

PMID- 16593520
TI  - Triazine herbicide resistance in the photosynthetic bacterium Rhodopseudomonas
      sphaeroides.
AB  - The photoaffinity herbicide azidoatrazine (2-azido-4-ethylamino-6-isopropylamino
      s-triazine) selectively labels the L subunit of the reaction center of the
      photosynthetic bacterium Rhodopseudomonas sphaeroides. Herbicide-resistant
      mutants retain the L subunit and have altered binding properties for methylthio-
      and chloro-substituted triazines as well as altered equilibrium constants for
      electron transfer between primary and secondary electron acceptors. We suggest
      that a subtle alteration in the L subunit is responsible for herbicide resistance
      and that the L subunit is the functional analog of the 32-kDa Q(B) protein of
      chloroplast membranes.

PMID- 16593521
TI  - Body size and food size in freshwater zooplankton.
AB  - We used double-label liquid scintillation techniques to measure the efficiencies
      with which eight different-sized zooplankton species ingested four cell types
      relative to a standard cell type (Chlamydomonas). Efficiency ratios (ERs:
      clearance rate on cell type X / clearance rate on Chlamydomonas) on the three
      ultraplankton (<5 mum in diameter) cells (a coccoid bacterium and the algae
      Synechococcus and Nannochloris) varied greatly among zooplankton species but were
      not correlated with zooplankton body length. Variation in ERs on a much larger
      (17 x 14 mum) algal cell (Cryptomonas) was only partly explained by zooplankton
      body length. The eight zooplankton species were classified into three functional
      groups: (i) species having moderate to high ERs on all ultraplankton (0.4 < ER <
      1.6) and ERs on Cryptomonas proportional to their body lengths (Conochilus,
      Diaphanosoma, and probably Keratella cochlearis and Ceriodaphnia); (ii) species
      having extremely low ERs on bacteria (mean ER < 0.05), higher but still low ERs
      on ultraphytoplankton (ER generally < 0.4), and ERs on Cryptomonas proportional
      to their body lengths (Bosmina, Diaptomus copepodites and adults); (iii) species
      having extremely low ERs on all ultraplankton (mean ER < 0.05) and ERs on
      Cryptomonas much higher than expected given their body lengths (Keratella crassa,
      Polyarthra, and Diaptomus nauplii). These functional groups follow neither
      taxonomic nor body-length groupings. We conclude that zooplankton body length may
      influence the maximal particle size a species can ingest but has little influence
      on the ingestion of smaller particles. Two frequently used models relating
      zooplankton body size and food size are unrealistic.

PMID- 16593522
TI  - On the mathematical theory of globally optimal planned economic systems.
AB  - Applying a theorem of non-negative matrix to an economic system, we obtain the
      rate of growth of the system and the ratio between the sectors of production.
      Accordingly, we establish a positive eigenvector method for planning economics.

PMID- 16593523
TI  - Superintegrable systems.
AB  - Families of matrix differential superintegrable systems of Lax type are
      constructed. Each family is a commutative Lie superalgebra with an infinite
      common set of conservation laws.

PMID- 16593524
TI  - Detection in vivo of a new gene product (gene III) of cauliflower mosaic virus.
AB  - Cauliflower mosaic virus DNA contains six major open reading frames (ORFs). As
      only the mRNA corresponding to the transcription of gene VI and its translation
      product have been isolated, the identification in infected plants of products
      corresponding to the five other putative genes remains to be established. The
      present paper reports the detection of an ORF III product by means of antibodies
      raised against an NH(2)-terminal synthetic peptide of 19 amino acids
      corresponding to a sequence predicted from the nucleotide sequence of ORF III.
      The detection of this gene product raises the question of the mechanism of its
      expression.

PMID- 16593525
TI  - Heat-labile alkaline phosphatase from Antarctic bacteria: Rapid 5' end-labeling
      of nucleic acids.
AB  - A heat-labile alkaline phosphatase has been purified to near homogeneity from
      HK47, a bacterial strain isolated from Antarctic seawater. The active form of the
      enzyme has a molecular weight of 68,000 and is uniquely monomeric. The optimal
      temperature for the enzymatic activity is 25 degrees C. Complete and irreversible
      thermal inactivation of the enzyme occurs in 10 min at 55 degrees C. By using
      this heat-labile enzyme for dephosphorylation followed by a 10-min heat
      treatment, rapid end-labeling of nucleic acids by T4 polynucleotide kinase has
      been achieved.

PMID- 16593526
TI  - Isolation and sequencing of two cerebellum-specific peptides.
AB  - By comparing the HPLC elution profiles of peptides isolated from different brain
      regions, two cerebellum-specific species have been identified. The peptides were
      isolated by sequential chromatography on reverse phase, followed by ion-pairing
      HPLC using alkane sulfates as pairing reagents. The sequences of both peptides
      have been determined by gasphase Edman degradation and carboxypeptidase Y
      analysis and were confirmed by synthesis. The larger peptide, termed cerebellin,
      is a hexadecamer of primary amino acid sequence NH(2)-Ser-Gly-Ser-Ala-Lys-Val-Ala
      Phe-Ser-Ala-Ile-Arg-Ser-Thr-Asn-His- OH. The second peptide is a pentadecamer
      with a primary sequence identical to residues 2-16 of cerebellin, the
      nomenclature of which is des-Ser(1)-cerebellin. Subcellular fractionation of
      cerebellum followed by ion-pairing HPLC analysis shows that both cerebellin and
      des-Ser(1)-cerebellin are enriched between 2.5- and 4-fold in the P2 crude
      synaptosomal fraction, suggesting their sequestration in some subcellular
      particle in vivo.

PMID- 16593527
TI  - Multicomponent RNA plant virus infection derived from cloned viral cDNA.
AB  - In vitro transcripts from mixtures of appropriate brome mosaic virus (BMV) cDNA
      clones are infectious when inoculated onto barley plants. Infectivity depends on
      in vitro transcription and on the presence of transcripts from clones of all
      three BMV genetic components. Infectivity is destroyed by RNase after
      transcription, but it is insensitive to RNase before or to DNase after
      transcription. Virion RNAs from plants infected with cDNA transcripts hybridize
      to BMV-specific probes and coelectrophorese with virion RNAs propagated from
      conventional inoculum. Direct RNA sequencing shows that a deletion in the
      noncoding region of one infectious BMV clone is preserved in viral RNA from
      plants systemically infected with transcript mixtures representing that clone.

PMID- 16593528
TI  - Phototropic response of the stage I Phycomyces sporangiophore to a pulse of blue
      light.
AB  - Positive phototropic curvature of Phycomyces sporangiophores (stage I) induced by
      a short pulse (10 sec) of blue light has been characterized. The curvature
      response, measured 40 min after irradiation, increases with increasing fluences
      up to approximately 10(-4) J.m(-2); it then decreases and becomes nearly 0 at a
      fluence of approximately 10(-1) J.m(-2). The threshold fluence is found near 10(
      7) J.m(-2), indicating over 1000-fold higher sensitivity than the first positive
      phototropism of grass coleoptiles. Positive curvature of the sporangiophore
      becomes detectable 5 min after irradiation and increases with time up to
      approximately 40 min. During the course of this curvature development, overall
      elongation growth of the sporangiophore is first stimulated and then inhibited.
      The relationship between the phototropic response and the response in overall
      elongation growth is discussed, and it is suggested that the primary mechanisms
      of these responses are distinct.

PMID- 16593529
TI  - Isometric embeddings of graphs.
AB  - We prove that any finite undirected graph can be canonically embedded
      isometrically into a maximum cartesian product of irreducible factors.

PMID- 16593530
TI  - On applications of diophantine approximations.
AB  - This paper is devoted to the study of the arithmetic properties of values of G
      functions introduced by Siegel [Siegel, C. L. (1929) Abh. Preuss. Akad. Wiss.
      Phys.-Math. Kl. 1]. One of the main results is a theorem on the linear
      independence of values of G-functions at rational points close to the origin. In
      this theorem, no conditions are imposed on the p-adic convergence of a G-function
      at a generic point. The theorem finally realizes Siegel's program on G-function
      values outlined in his paper.

PMID- 16593531
TI  - Reduction of scattering to an invariant finite displacement in an ambient space
      time.
AB  - The scattering transformation S for a wave equation in Minkowski space M(0) is
      reducible (rigorously in the classical case, necessarily partially heuristically
      in the nonlinear quantum case) to the action of a distinguished finite
      transformation zeta in the ambient universal cosmos M. M(0) is invariantly
      imbedded in M, relative to any given point of observation, and the space-like
      surfaces x(0) = s in M(0) converge as s --> +/-infinity to finite light cones
      C(+/-) in M. The generator zeta of the infinite cyclic center of the connected
      group of all casuality-preserving transformations in M (isomorphic to
      SU(2,2)/Z(2)) carries C(-) into C(+) and acts on solutions of relativistic wave
      equations as S, in an invariant bundle formulation. The establishment of S is
      simplified, the symmetry and regularity properties of S are enhanced, the scope
      of the scattering concept is extended to important equations such as those of
      Yang-Mills (lacking an invariant separation into free and interaction
      components), and the treatment of bound and scattering states is more unified.

PMID- 16593532
TI  - Topology of bonding in pi-electron systems.
AB  - Delocalization in conjugated pi-electron systems is shown to be closely related
      to the topological concept of connectivity. A topological bond order is defined
      as a quantitative measure of the extent to which the subspace of a pair of
      adjacent atoms approximates a disconnected component of the molecular topological
      space. The agreement between this measure and molecular-orbital bond orders in
      the ordering of bond strengths within molecules is near perfect. There is also
      excellent quantitative agreement between these two measures of bond strength.
      Bond orders appear to be primarily determined by molecular topology. A new type
      of intramolecular equivalence relation between bonds, called "coresiduality,"
      emerges from the topological analysis. Two bonds are coresidual if the residues
      remaining when each pair of adjacent atoms is excised from the molecule are
      isomorphic. Coresidual bonds have equal bond orders. Coresiduality includes, but
      is more general than, equivalence due to symmetry.

PMID- 16593533
TI  - Light-harvesting II (B800-B850 complex) structural genes from Rhodopseudomonas
      capsulata.
AB  - The light-harvesting II (LHII) structural genes coding for the (B800-B850
      complex) beta- and alpha-polypeptides have been cloned and the nucleotide and
      deduced polypeptide sequences have been determined. This completes the sequencing
      of all seven structural genes coding for the structural polypeptides of the
      photosynthetic apparatus that bind the pigments and cofactors participating in
      the primary light reactions of photosynthesis. Unlike the structural genes coding
      for the reaction center L, M, and H subunits and the light-harvesting I (LHI)
      (B870 complex) structural polypeptides, the LHII structural genes are not within
      the 46-kilobase photosynthetic gene cluster carried by the R-prime plasmid
      pRPS404. Identical organization of the beta and alpha structural genes for both
      LHI and LHII and sequence homologies between the two beta-polypeptides and
      between the two alpha-polypeptides suggests that both complexes arose by gene
      duplication from a single ancestral light-harvesting complex and that the
      putative bacteriochlorophyll binding sequence Ala-X-X-X-His has been absolutely
      conserved.

PMID- 16593534
TI  - Expression of phaseolin cDNA genes in yeast under control of natural plant DNA
      sequences.
AB  - We have constructed a strain of Saccharomyces cerevisiae that expresses two
      different members of the multigene family encoding phaseolin, the major seed
      storage glycoprotein from the French bean, Phaseolus vulgaris. Yeast vector
      plasmids have been engineered to include a Phaseolus DNA segment that contains
      the natural 5' and 3' plant genomic regulatory sequences flanking a cDNA copy of
      the protein-encoding region. Characterization of phaseolin transcripts isolated
      from transformed yeast cells revealed the presence of two classes of
      polyadenylylated RNA, approximately 1400 and 1800 bases, which initiate and
      terminate in plant DNA sequences. Protein extracts from transformants contain
      phaseolin-immunoreactive proteins similar in size to those isolated from plant
      tissue. These polypeptides are glycosylated in yeast and their molecular weights
      are consistent with the possibility that the phaseolin signal peptide has been
      cleaved to form the mature protein.

PMID- 16593535
TI  - Light-harvesting chlorophyll a/b-protein: Three-dimensional structure of a
      reconstituted membrane lattice in negative stain.
AB  - The three-dimensional structure of a negatively stained hexagonal membrane
      lattice containing the light-harvesting chlorophyll a/b-protein complex and
      phospholipids has been determined to 30-A resolution by image reconstruction from
      electron micrographs. This lattice has p321 symmetry, a lattice constant of 125 A
      and a thickness of 75 A. The monomer is shown to be an elongated molecule about
      65 A long in the dimension perpendicular to the plane of the membrane. It spans
      the hydrophobic domain of the membrane in an asymmetric fashion, projecting
      [unk]20 A from one surface and less from the other. On the basis of this image
      and available biochemical data, the structure of the complex in the native
      thylakoid membrane is proposed.

PMID- 16593536
TI  - Cation binding by bacteriorhodopsin.
AB  - We have found that extensively washed purple membrane has about 1 calcium and 3-4
      magnesium ions bound per bacteriorhodopsin molecule. When these divalent cations
      are removed by any of a variety of means, the pigment changes its color from
      purple to blue (lambda(max) approximately 600 nm). This blue pigment, which can
      be formed at near neutral pH, is probably very similar to blue species formed
      when the pH of a purple membrane sample is lowered to approximately 2. When any
      of a wide variety of cations are added to a blue membrane preparation, the
      characteristic purple color of bacteriorhodopsin returns. Divalent and trivalent
      cations are much more efficient than monovalent cations in restoring the purple
      color and are effective at a ratio approaching one cation per pigment molecule.
      Besides shifting the absorption spectrum, removal of the divalent cations
      drastically alters the photochemical cycle of bacteriorhodopsin, including
      abolishing the unprotonated Schiff base (M-type) intermediate. Finally, lanthanum
      not only displaces the divalent cations normally bound to the purple membrane but
      also greatly reduces both the rate of decay of the M412 intermediate and proton
      uptake.

PMID- 16593537
TI  - Cloning determinants of pathogenesis from Pseudomonas syringae pathovar syringae.
AB  - Transposon mutagenesis and a cosmid genomic library of DNA from the bean pathogen
      Pseudomonas syringae pathovar syringae were used to identify and isolate
      sequences essential for pathogenesis. Strain PS9021, derived by Tn5 mutagenesis,
      was determined to be nonpathogenic on Phaseolus vulgaris cultivar Red Mexican and
      incapable of inducing a hypersensitive response in Nicotiana tabacum. This mutant
      also produced fluidal rather than firm colonies on selected agar media. A Tn5
      containing EcoRI fragment from PS9021 was cloned and used to probe 1500 members
      of a genomic library constructed with DNA from the pathogenic parent strain and
      the wide host range cosmid pVK102. One member that hybridized to the probe
      contained a cosmid with a 30-kilobase-pair insert (pOSU3101) that complemented
      the mutant phenotypes when mobilized into PS9021. A restriction endonuclease
      cleavage site map of pOSU3101 was constructed and sequences essential for
      pathogenesis were determined by subcloning. Approximately 8.5 kilobase pairs of
      the insert were essential for restoration by complementation of pathogenesis and
      hypersensitive response and wild-type colony morphology in strain PS9021.

PMID- 16593538
TI  - Highly structured sequence homology between an insertion element and the gene in
      which it resides.
AB  - The recessive allele for soybean seed lectin results from the insertion of a DNA
      segment (designated Tgm1) into the coding region of the gene. The termini of Tgm1
      display structural features characteristic of a transposable element. The
      complete sequence of Tgm1 contains 3550 base pairs (bp) and can be divided into
      three regions (left arm, mid-section, and right arm). No large open reading
      frames were found, but an extensive, highly structured border with homology to
      the lectin gene was revealed. The left border (726 bp) comprising most of the
      left arm and extreme right border (144 bp) of the right arm consist of various
      forms of a basic 54-bp repeating unit. This 54-bp unit is comprised of a stem
      loop structure and interhairpin sequence that occurs 13 times in the left arm and
      2 times in the right arm of Tgm1. Progressively degenerate forms of this
      repeating unit appear toward the termini of Tgm1, but the dyad symmetry remains
      highly conserved. Seven nucleotides (A-C-A-T-C-G-G and its complement) maintained
      within the stem also appear as a subset of inverted repeats found at nearly equal
      distances from the target site in the lectin gene. Together with the inverted
      repeat termini and a duplication in the left arm, this 7-bp sequence occurs a
      total of 33 times in Tgm1. We infer that the dyad symmetries containing this
      sequence are involved in target gene selection. The repeating unit format of Tgm1
      describes a distinct class of eukaryotic elements that includes representatives
      known to be mobile in snapdragon and maize.

PMID- 16593539
TI  - Repair of defined single base-pair mismatches in Escherichia coli.
AB  - Heteroduplexes with single base-pair mismatches of known sequence were prepared
      by annealing separated strands of bacteriophage lambda DNA and used to transfect
      Escherichia coli. Each of the eight possible single base-pair mismatches was
      constructed. Genetic analysis of the progeny phages obtained from transfected
      bacteria indicates that the E. coli mismatch repair system does not recognize (or
      does not repair) all single base-pair mismatches with equal efficiency. In
      particular, the A.G, C.T, and C.C mismatches appear to be less repaired than any
      others. The mutator character of mismatch repair-deficient mutants suggests that
      such unrepaired mismatches should occur infrequently during E. coli DNA
      replication.

PMID- 16593540
TI  - Evolution of green plants as deduced from 5S rRNA sequences.
AB  - We have constructed a phylogenic tree for green plants by comparing 5S rRNA
      sequences. The tree suggests that the emergence of most of the uni- and
      multicellular green algae such as Chlamydomonas, Spirogyra, Ulva, and Chlorella
      occurred in the early stage of green plant evolution. The branching point of
      Nitella is a little earlier than that of land plants and much later than that of
      the above green algae, supporting the view that Nitella-like green algae may be
      the direct precursor to land plants. The Bryophyta and the Pteridophyta separated
      from each other after emergence of the Spermatophyta. The result is consistent
      with the view that the Bryophyta evolved from ferns by degeneration. In the
      Pteridophyta, Psilotum (whisk fern) separated first, and a little later
      Lycopodium (club moss) separated from the ancestor common to Equisetum
      (horsetail) and Dryopteris (fern). This order is in accordance with the classical
      view. During the Spermatophyta evolution, the gymnosperms (Cycas, Ginkgo, and
      Metasequoia have been studied here) and the angiosperms (flowering plants)
      separated, and this was followed by the separation of Metasequoia and Cycas
      (cycad)/Ginkgo (maidenhair tree) on one branch and various flowering plants on
      the other.

PMID- 16593541
TI  - A cosmid for selecting genes by complementation in Aspergillus nidulans:
      Selection of the developmentally regulated yA locus.
AB  - We constructed a 9.9-kilobase cloning vector, designated pKBY2, for isolating
      genes by complementation of mutations in Aspergillus nidulans. pKBY2 contains the
      bacteriophage lambda cos site, to permit in vitro assembly of phage particles; a
      bacterial origin of replication and genes for resistance to ampicillin and
      chloramphenicol, to permit propagation in Escherichia coli; the A. nidulans
      trpC(+) gene, to permit selection in Aspergillus; and a unique BamHI restriction
      site, to permit insertion of DNA fragments produced by digestion with restriction
      endonucleases BamHI, BglII, Mbo I, or Sau3A. We used this cosmid to form a
      quasirandom recombinant DNA library containing 35- to 40-kilobase DNA fragments
      from a wild-type strain of A. nidulans. DNA from this library transformed a
      yellow-spored (yA(-)) pabaA(-)trpC(-)Aspergillus strain (FGSC237) to trpC(+) at
      frequencies of approximately 10 transformants per mug of DNA. Three of
      approximately 1000 trpC(+)pabaA(-) colonies obtained were putative yA(+)
      transformants, because they produced wild-type (green) spores. DNA from each of
      the green-spored transformants contained pKBY2 sequences and DNA from two
      transformants transduced E. coli to ampicillin resistance following treatment in
      vitro with a lambda packaging extract. The cosmids recovered in E. coli had
      similar restriction patterns and both yielded trpC(+) transformants of A.
      nidulans FGSC237, 85% of which produced green spores. Several lines of evidence
      indicate that the recovered cosmids contain a wild-type copy of the yA gene.

PMID- 16593542
TI  - Nucleotide sequence of F(0)-ATPase proteolipid (subunit 9) gene of maize
      mitochondria.
AB  - The F(0)-ATPase proteolipid, also referred to as subunit 9 or the
      dicyclohexylcarbodiimide-binding protein, is encoded by a mitochondrial gene in
      maize that we have designated atp 9. The clone containing atp 9 was selected for
      investigation from a mitochondrial DNA library because of its abundant transcript
      in total maize mitochondrial RNA preparations. Sequence analysis of the clone
      revealed an open reading frame that was readily identified by its nucleotide
      homology with the ATPase subunit 9 gene of yeast. As deduced from the nucleotide
      sequence, the maize ATPase subunit 9 protein contains 74 amino acids with a
      molecular weight of 7368. Substantial amino acid sequence homology is conserved
      among maize, yeast, bovine, and Neurospora mitochondrial ATPase subunit 9
      proteins, regardless of whether the gene is nuclearly encoded (bovine and
      Neurospora) or mitochondrially encoded (yeast and maize). RNA transfer blot
      analysis indicated that the gene sequence is actively transcribed, producing an
      initial transcript that is large and extensively processed.

PMID- 16593543
TI  - Nitrogenase reductase: A functional multigene family in Rhizobium phaseoli.
AB  - The complete coding sequence of the nitrogenase reductase gene (nifH) is present
      in three different regions of a Rhizobium phaseoli symbiotic plasmid. Homology
      between two of the regions containing nifH coding sequences extends over 5
      kilobases. These in turn share 1.3 kilobases of homology with the third region.
      The nucleotide sequences of the three nitrogenase reductase genes were found to
      be identical. Site-directed insertion mutagenesis indicated that none of the
      three genes is indispensable for nitrogen fixation during symbiosis with
      Phaseolus vulgaris. This implies that at least two of the reiterated genes can be
      functionally expressed.

PMID- 16593544
TI  - The Markoff-Duffin-Schaeffer inequalities abstracted.
AB  - The kth Markoff-Duffin-Schaeffer inequality provides a bound for the maximum,
      over the interval -1 </= x </= 1, of the kth derivative of a normalized
      polynomial of degree n. The bound is the corresponding maximum of the Chebyshev
      polynomial of degree n, T = cos(n cos(-1)x). The requisite normalization is over
      the values of the polynomial at the n + 1 points where T achieves its extremal
      values. The inequality is an equality only if the polynomial equals T or -T. The
      proof uses complex variable theory. This paper deals with a well-known
      generalization of polynomials-namely, functions satisfying some of the
      oscillation and approximation properties of ordinary polynomials. In particular,
      the generalized Chebyshev polynomial exhibits the extremal oscillations
      characteristic of the classical Chebyshev polynomial. It is shown that the direct
      analogs of the Markoff-Duffin-Schaeffer inequalities hold in this abstract
      setting and that they are included as a special case. Moreover, the proof is more
      elementary.

PMID- 16593546
TI  - Note on four-particle wave functions.
AB  - Dougall's expansion is used in the expression for the volume element in
      tetrahedral coordinates, thereby lifting the spherical triangle restriction on
      the angles at the tetrahedral vertex. Application is made to the evaluation of
      matrix elements for the ground state of three-electron atoms.

PMID- 16593545
TI  - Group actions and higher signatures.
AB  - Let pi be a nontrivial finite group and M be a closed manifold. An interesting
      question is whether or not M has the R-homology type of a manifold admitting a
      free pi action. Here this problem is studied for actions that are "homologically
      trivial." If pi(1)M is nontrivial these questions are intimately related to the
      Novikov higher signature conjecture, but the results are new even in the simply
      connected case.

PMID- 16593547
TI  - Purification and characterization of polynucleotide phosphorylase from cucumber.
AB  - Polynucleotide phosphorylase (polyribonucleotide:orthophosphate
      nucleotidyltransferase, EC 2.7.7.8) activity has been found in many prokaryotes
      and studied in detail since 1955. Such enzymes have been detected also in plants.
      We now describe the purification of polynucleotide phosphorylase from cucumber
      cotyledons and leaves. This enzyme is a complex of three subunits, possibly not
      identical, of about M(r) 50,000. Its enzymatic properties are similar to those of
      the tobacco enzyme. Unlike the prokaryotic enzymes, the plant enzyme shows
      activity in the absence of primer but is to various extents stimulated by various
      ribopolynucleotides or RNAs. RNA-dependent RNA polymerase, not previously shown
      to exist in non-virus-infected cucumber, has been found to be present at a low
      level and was separated from the much greater amount of polynucleotide
      phosphorylase, although some of the physical properties of the two enzymes are
      rather similar.

PMID- 16593548
TI  - Ochromonas mitochondria contain a specific chloroplast protein.
AB  - Antibody raised against the small subunit of ribulose-1,5-bisphosphate
      carboxylase [3-phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39] of
      Chlamydomonas reinhardtii labeled the mitochondria as well as the chloroplast of
      the chrysophyte alga Ochromonas danica in sections prepared for immunoelectron
      microscopy by the protein A-gold technique. The same antibody labeled the
      chloroplast but not the mitochondria of C. reinhardtii. A quantitative study of
      labeling in dark-grown, greening (32 hr light), and mature green cells of O.
      danica revealed that anti-small-subunit staining in the mitochondria increased
      progressively in the light as it does in the plastid. Antibody to the large
      subunit of the enzyme did not label the mitochondria of either O. danica or C.
      reinhardtii. In view of the recent demonstrations of homologous DNA sequences in
      the mitochondrial and chloroplast genomes of higher plants, we suggest that the
      DNA sequence coding for the small subunit has migrated to the mitochondria from
      nucleus or chloroplast and is expressed within the organelle.

PMID- 16593549
TI  - Efficient induction and selection of chloroplast-encoded antibiotic-resistant
      mutants in Nicotiana.
AB  - A high rate of plastome-encoded mutations was induced in Nicotiana by exposing
      seeds to N-nitroso-N-methylurea. Seeds then were subjected to nutritional and in
      vitro selection procedures for systematic isolation of plastome-dependent
      antibiotic-resistant plants. Multiple flowering lines resistant to streptomycin,
      spectinomycin, lincomycin, or chloramphenicol were obtained. A detailed analysis
      of the streptomycin-resistant lines is presented. Sexual hybridization, cybrid
      formation following protoplast fusion, and in organello protein synthesis were
      used to rigorously assign the mutations to the chloroplast genome. The efficient
      rates of mutagenesis combined with the in vitro mass-screening procedures
      described here should facilitate investigation of fundamental aspects of
      chloroplast genetics in higher plants.

PMID- 16593550
TI  - Spectrum and chemical composition of the remarkable planetary nebula NGC 6537.
AB  - Observations with the image tube scanner at the Shane 3-m telescope are combined
      with data obtained with the International Ultraviolet Explorer to assess the
      spectrum of the remarkable high-excitation planetary nebula NGC 6537. We have
      analyzed the spectrum of this nitrogen-rich object with the aid of the
      theoretical nebular models. The models permit one to estimate the fraction of
      unobservable ions of abundant elements. On the scale log N(H) = 12, the
      logarithmic abundance values for He, C, N, and O are as follows: [Table: see
      text] The abundances of Ne S, Cl, and Ar appear to be essentially solar to within
      a factor of 2. Our interpretation is that the progenitor of NGC 6537 had a
      chemical composition not differing greatly from that of the Sun. In the course of
      its prenebular evolution, C and probably O were converted to N and much H was
      converted to helium.

PMID- 16593551
TI  - Correlation between catalytic activity and bonding and coordination number of
      atoms and molecules on transition metal surfaces: Theory and experimental
      evidence.
AB  - Correlation between catalytic activity and low-energy local electronic
      fluctuations in transition metals is proposed. A theory and calculations are
      presented which indicate that maximum electronic fluctuations take place at high
      coordination metal sites. Either (i) atomically rough surfaces that expose to the
      reactant molecules atoms with large numbers of nonmagnetic or weakly magnetic
      neighbors in the first or second layer at the surface or (ii) stepped and kinked
      surfaces are the most active in carrying out structure-sensitive catalytic
      reactions. The synthesis of ammonia from N(2) and H(2) over iron and rhenium
      surfaces, (1)H(2)/(2)H(2) exchange over stepped platinum crystal surfaces at low
      pressures, and the hydrogenolysis (C-C bond breaking) of isobutane at kinked
      platinum crystal surfaces are presented as experimental evidence in support of
      the theory.

PMID- 16593552
TI  - Pade approximations and diophantine geometry.
AB  - Using methods of Pade approximations we prove a converse to Eisenstein's theorem
      on the boundedness of denominators of coefficients in the expansion of an
      algebraic function, for classes of functions, parametrized by meromorphic
      functions. This result is applied to the Tate conjecture on the effective
      description of isogenies for elliptic curves.

PMID- 16593553
TI  - Harmonic maps of S into a complex Grassmann manifold.
AB  - Let G(k, n) be the Grassmann manifold of all C(k) in C(n), the complex spaces of
      dimensions k and n, respectively, or, what is the same, the manifold of all
      projective spaces P(k-1) in P(n-1), so that G(1, n) is the complex projective
      space P(n-1) itself. We study harmonic maps of the two-dimensional sphere S(2)
      into G(k, n). The case k = 1 has been the subject of investigation by several
      authors [see, for example, Din, A. M. & Zakrzewski, W. J. (1980) Nucl. Phys. B
      174, 397-406; Eells, J. & Wood, J. C. (1983) Adv. Math. 49, 217-263; and Wolfson,
      J. G. Trans. Am. Math. Soc., in press]. The harmonic maps S(2) --> G(2, 4) have
      been studied by Ramanathan [Ramanathan, J. (1984) J. Differ. Geom. 19, 207-219].
      We shall describe all harmonic maps S(2) --> G(2, n). The method is based on
      several geometrical constructions, which lead from a given harmonic map to new
      harmonic maps, in which the image projective spaces are related by "fundamental
      collineations." The key result is the degeneracy of some fundamental
      collineations, which is a global consequence, following from the fact that the
      domain manifold is S(2). The method extends to G(k, n).

PMID- 16593554
TI  - Fluctuation of the Ca-sequestering activity of permeabilized sea urchin embryos
      during the cell cycle.
AB  - We have followed the sequestration of Ca(2+) by intracellular compartments in sea
      urchin embryos through the first cell cycles. To gain biochemical access to these
      compartments, the embryos were permeabilized by brief exposure to an intense
      electric field. Sequestration was determined as the retention of tracer, (45)Ca,
      after filtration of aliquots on Millipore filters. The permeabilized cells
      sequester Ca(2+) at a constant rate for at least 20 min, with the following
      characteristics: (i) ATP is required. (ii) Sequestration occurs at Ca(2+) levels
      corresponding to those estimated in vivo. (iii) The Ca(2+) concentration
      dependence of sequestration and its insensitivity to mitochondrial poisons imply
      that the activity derives from a single, nonmitochondrial transport system. The
      Ca(2+)-sequestering activities of embryos that are permeabiized at successive
      stages of the first cell cycle (one-cell stage) progressively increase to 5 times
      the initial level. The rate of sequestration is maximal during telophase and, in
      some populations of zygotes, is nearly as great throughout prophase. Over the
      course of the second cell cycle (two-cell stage), the activity undergoes a 2-fold
      oscillation that bears the same temporal relationship to mitosis as the previous
      fluctuation.

PMID- 16593555
TI  - Persistence and coexistence of a nonsymbiotic coral in open reef environments.
AB  - In the Republic of Belau (western Caroline Islands), the nonsymbiotic stony coral
      Tubastraea micrantha (Ehrenberg) occurs commonly on open reef habitats that are
      dominated by symbiotic corals. This observation calls into question the often
      held view that nonsymbiotic corals are restricted to cryptic environments because
      of their inability to compete successfully for space with rapidly growing
      symbiotic corals. In this study, we investigated aspects of the biology of
      Tubastraea that might account for its coexistence and persistence on the reef.
      Our results indicate that despite low calcification rates, linear skeletal
      extension for Tubastraea is surprisingly rapid for a nonsymbiotic species and
      comparable to those of many symbiotic corals. This factor, coupled with
      Tubastraea's resistance to direct competitive dominance (i.e., by aggressive
      interactions) and avoidance of predation, promotes its coexistence with symbiotic
      species. The relative importance of these biological interactions in different
      coral communities leads to predictions corroborated by observed patterns of local
      distribution and abundance.

PMID- 16593556
TI  - Negative control for the initiation of meiosis in Schizosaccharomyces pombe.
AB  - Temperature-sensitive mutants of the pat1 gene of Schizosaccharomyces pombe are
      able to produce poorly viable spores from the haploid state without the
      requirement for nitrogen starvation if exposed to the restrictive temperature.
      Three lines of evidence strongly suggest that this gene codes for a factor whose
      physiological role is inhibition of initiation of meiosis. First, pat1 haploids
      arrested in G(1) phase undergo apparent premeiotic DNA synthesis at the
      restrictive temperature. Second, the pat1 gene was found to exert its function at
      a specified stage of the meiotic pathway by comparison with other meiotic
      mutants. Third, meiotic recombination and chromosome segregation take place quite
      normally in pat1 diploids at the restrictive temperature, resulting in the
      production of highly viable spores. A negative control mechanism for meiosis is
      proposed.

PMID- 16593557
TI  - Modified cryptochrome in vivo absorption in dim photosporulation mutants of
      Trichoderma.
AB  - Mutants of Trichoderma harzianum that are defective in blue-light-induced
      sporulation were induced by nutritional stresses as an alternative to light.
      These mutants may be modified in the putative photoreceptor pigment
      "cryptochrome" or in an early transduction component. dim (dimsighted) mutants
      induced by a short transient stress were mapped into four complementation groups
      and were chosen for study of pigment deficiencies by in vivo absorption
      spectroscopy. Mutants rib(-)10 and lys(-)44 in the dimY complementation group had
      altered in vivo absorption spectra in the blue region. Difference spectra
      obtained by subtracting dimY spectra from that of the wild type had difference
      bands with peaks at 455 and 480 nm. The similarity between the in vivo difference
      spectra and the action spectrum for sporulation in wild-type Trichoderma suggests
      that the mutants lack cryptochrome or have a defective cryptochrome. The decrease
      in photoresponse as well as the modification of the action spectrum near 480 nm
      in a dimY mutant support these suggestions. Both dimY mutants pleiotropically
      accumulate a yellow water-soluble pigment absorbing at wavelengths lower than the
      blue maxima of cryptochrome; this yellow pigment may be related to cryptochrome.

PMID- 16593558
TI  - alpha-Amanitin resistance is developmentally regulated in carrot.
AB  - Carrot cells are capable of inactivating alpha-amanitin only in embryogenic
      conditions (regenerating cells and embryoids). Instead, the mutant line a3 is
      capable of inactivating the drug also in nonembryogenic conditions (vegetative
      growth). The mutation is dominant in somatic hybrids and is pleiotropic, allowing
      expression during vegetative growth of other embryonal functions. The
      inactivation of alpha-amanitin is due to the oxidative activity of tyrosinase.

PMID- 16593559
TI  - Kin discrimination by worker honey bees in genetically mixed groups.
AB  - We tested the hypothesis that in a genetically mixed assemblage of worker honey
      bees, individual workers would behave differently toward unfamiliar sisters than
      toward unfamiliar nonsisters. Groups of worker honey bees of mixed genetic
      composition were assembled by collecting pupae from separate colonies and placing
      the worker bees together on eclosion. A total of 10 workers, 5 from each of two
      kin groups, were used to form each group. When the workers were 5 days old, a
      worker of one of the two kin groups was introduced into the mixed group. This
      worker had previously been held in a group of its sisters, without contact with
      queen or nonsister bees. The interactions with the introduced bee indicate that
      in a mixed kin group, individual workers learn the composite identity of the
      group and do not attack unfamiliar bees differentially on the basis of kinship.
      However, kinship does influence the total number of interactions in which an
      introduced bee engages when placed in a genetically mixed group; bees interacted
      significantly more often with sisters than with nonsisters. There was a trend for
      bees to be involved in more feeding interactions with sisters. This finding
      indicates an ability of a bee to learn and use its own cues. In mixed groups,
      each bee maintains its genotypically correlated identity; the bees' odors do not
      comingle into a "group" or "gestalt" odor. The significance of these results is
      discussed in light of the genetic structure of natural colonies of honey bees.

PMID- 16593560
TI  - Maass cusp forms.
AB  - It is shown that, under certain standard assumptions, such as extended Riemann
      hypotheses, the scattering matrix varphi(s) for generic Gamma </= SL(2, R) is
      unexpectedly of order 2. This leads to the conjecture that the generic cofinite
      Gamma has very few Maass cusp forms.

PMID- 16593561
TI  - Tobacco chloroplast tRNA(UUU) gene contains a 2.5-kilobase-pair intron: An open
      reading frame and a conserved boundary sequence in the intron.
AB  - The nucleotide sequence of a tRNA(Lys)(UUU) gene on tobacco (Nicotiana tabacum)
      chloroplast DNA has been determined. This gene is located 215 base pairs upstream
      from the gene for the 32,000-dalton thylakoid membrane protein on the same DNA
      strand and has a 2526-base-pair intron in the anticodon loop. The intron boundary
      sequence does not follow the G-U/A-G rule but is similar to those of tobacco
      chloroplast split genes for tRNA(Gly)(UCC) and ribosomal proteins L2 and S12. The
      intron contains one major open reading frame of 509 codons. The codon usage in
      the open reading frame resembles those observed in the genes for tobacco
      chloroplast proteins so far analyzed. The primary transcript of this tRNA gene is
      2.7 kilobases long.

PMID- 16593562
TI  - Nucleotide sequence of bean golden mosaic virus and a model for gene regulation
      in geminiviruses.
AB  - We have sequenced the genome of bean golden mosaic virus, which comprises two
      circular single-stranded DNA molecules (2646 and 2587 nucleotides long) of mostly
      unique sequence. Comparison of the sequences of bean golden mosaic virus and of
      cassava latent virus, which share serological relationship but are very different
      in host range and geographical origin, shows that each virus has a unique 200
      nucleotide sequence (common region) on each 2.6-kilobase molecule of its genome.
      The common regions of the two viruses have no sequence homology except for a
      short inverted repeat near the 3' end. Six open reading frames were identified
      that possess considerable sequence homology between the two viruses and, in bean
      golden mosaic virus, may encode proteins of 15.6, 19.6, 27.7, 29.7, 33.1, and
      40.2 kDa. Conserved open reading frames are found in both the viral strand and
      the complementary strand, are approximately the same size, and are in the same
      orientation with respect to the common region in both viruses. We propose that
      temporal regulation in geminiviruses depends on the polarity of transcription and
      that the common region represents a replication origin and contains elements that
      serve to modulate gene expression.

PMID- 16593563
TI  - An RNA-DNA copolymer whose synthesis is correlated with the transcriptional
      requirement for chromosomal initiation in Bacillus subtilis contains ribosomal
      RNA sequences.
AB  - During synchronous replication induced in a temperature-sensitive initiation
      mutant of Bacillus subtilis, we previously isolated an RNA covalently linked to
      DNA. This molecule was synthesized at specific times, correlated with the period
      of transcription that is required to initiate a new round of replication. In this
      paper, we show that both RNA and DNA components of the RNA-DNA molecule
      hybridized with the coding strand for ribosomal RNA. Competition hybridization
      experiments also demonstrated that ribosomal RNA sequences represent the great
      majority of the RNA that is linked to DNA. Both RNA and DNA components of the RNA
      DNA molecule also hybridized with a region close to the origin of replication, in
      particular with E19 and E22, two restriction fragments that are replicated early.
      These fragments in fact form part of the ribosomal operon rrnO. The role of the
      RNA-linked DNA molecule in initiation in B. subtilis and the possibility that
      this molecule emanates directly from rrnO rather than from other ribosomal RNA
      genes are discussed.

PMID- 16593564
TI  - Regulation of methionine synthesis in Escherichia coli: Effect of metJ gene
      product and S-adenosylmethionine on the expression of the metF gene.
AB  - The regulation of the expression of the Escherichia coli metF gene, which codes
      for 5,10-methylenetet-rahydrofolate reductase (EC 1.1.99.15), has been
      investigated by using a simplified DNA-directed in vitro system that measures the
      formation of the first dipeptide (fMet-Ser) of the gene product. The synthesis of
      fMet-Ser directed by a plasmid containing the metF gene is specifically inhibited
      by metJ protein (repressor protein). S-Adenosylmethionine enhances the inhibition
      by the metJ protein of metF gene expression. The inhibition by the metJ protein
      is at the level of transcription and the results suggest that S
      adenosylmethionine is functioning as an allosteric effector.

PMID- 16593565
TI  - Elongation in the major direction of tobacco mosaic virus assembly.
AB  - Butler and Lomonossoff [Butler, P. J. G. & Lomonossoff, G. P. (1978) J. Mol.
      Biol. 126, 877-882] claim that the elongation in the major direction (3'-->5')
      proceeds by incorporation of disk protein in tobacco mosaic virus (TMV) assembly.
      The strongest argument they have for this theory is the periodicity of 50 or 100
      nucleotides that they observed in the banding pattern of the protected RNAs
      during the first few minutes of the assembly reaction. We repeated their
      experiment using TMV-OM (a common Japanese strain) disk protein and TMV-OM RNA.
      We observed a banding pattern similar to theirs, but we found the long protected
      RNA at 6 min to be from the 260-nm intermediate particle rather than from the
      full-length TMV RNA. We also carried out the assembly reaction between TMV-OM
      disk protein, as well as cucumber green mottle mosaic virus (CGMMV) protein, and
      three strains of TMV RNAs. During the course of each assembly reaction, we
      examined the banding patterns. We demonstrated that the banding pattern of the
      protected RNA differs depending on what kind of RNA is used, rather than on what
      kind of aggregational state the protein is in. Specifically, the similar banding
      pattern observed for CGMMV subunit protein was also observed for TMV disk protein
      in the assembly reaction with TMV (OM) RNA. We showed previously that the
      assembly reaction between CGMMV protein and TMV RNA proceeds by incorporation of
      CGMMV subunit protein. This strongly indicates that the banding pattern of the
      protected RNA does not arise from the stepwise addition of the 20S disk protein.

PMID- 16593566
TI  - Anomalous properties of a simple small-volume membrane transport system at steady
      state.
AB  - We investigate the transport of a single ligand L, between two macroscopic baths
      with different concentrations of L, by a simple membrane system. The center of
      this system is a very small volume V that might contain N = 0, 1, 2,... molecules
      of L. Access to V from either bath is by means of a single binding site for L.
      The steady-state properties of this simple system are studied exactly by a
      discrete-N master-equation approach. It is found that the mean concentration of L
      in V, c = N/V, is not a significant quantity either kinetically or
      thermodynamically. Further, the chemical potential of L in V is not defined and
      hence the overall thermodynamic force on L between the two baths cannot be
      subdivided at V. In fact, because V is small, the transport system must be
      treated as an indivisible system with interdependent parts. In the limit when V
      and N are very large, V becomes in effect a third macroscopic bath and two well
      defined transport subsystems emerge (between V and either bath).

PMID- 16593567
TI  - Importance of bound divalent cations to the tyrosine deprotonation during the
      photocycle of bacteriorhodopsin.
AB  - The transient absorption changes occurring at 297 nm during the photocycles of
      the deionized and acidified bacteriorhodopsins (blue membranes) were studied. As
      opposed to what happens during the photocycle of the purple membrane, for the
      blue membranes only the fast absorption increase corresponding to trans-cis
      isomerization of the retinal chromophore is present; the slow rise attributed to
      the tyrosine deprotonation is not observed. The addition of different salts to
      the deionized membrane restores the original color and causes a tyrosine
      deprotonation during the photocycle. This suggests that the presence of cations
      is required for the deprotonation of tyrosine as it is for the deprotonation of
      the retinylidene Schiff base. These results are discussed in terms of the
      recently proposed cation model for the observed deprotonation processes in the
      photocycle of bacteriorhodopsin.

PMID- 16593568
TI  - A model of protein conformational substates.
AB  - Many proteins have been observed to exist in a large number of conformations that
      are believed to play an important role in their dynamics. A model of protein
      conformational substates that incorporates the ideas of frustration and disorder
      in analogy to glasses and spin glasses is proposed. Applications to x-ray
      diffraction, Mossbauer studies, and recombination experiments are discussed.

PMID- 16593569
TI  - Betaine synthesis in chenopods: Localization in chloroplasts.
AB  - PLANTS FROM SEVERAL FAMILIES (CHENOPODIACEAE, GRAMINEAE, COMPOSITAE) ACCUMULATE
      BETAINE (GLYCINE BETAINE) IN RESPONSE TO SALT OR WATER STRESS VIA THE PATHWAY:
      choline --> betainal (betaine aldehyde) --> betaine. Betaine accumulation is
      probably a metabolic adaptation to stress. Intact protoplasts from leaves of
      spinach (Spinacia oleracea) oxidized [(14)C]choline to betainal and betaine, as
      did protoplast lysates. Upon differential centrifugation, the [(14)C]choline
      oxidizing activity of lysates sedimented with chloroplasts. Chloroplasts purified
      from protoplast lysates by a Percoll cushion procedure retained strong
      [(14)C]choline-oxidizing activity (1-3 nmol/mg of chlorophyll per hr), although
      the proportion of the intermediate, [(14)C]betainal, in the reaction products was
      usually higher than for protoplasts. Isolated chloroplasts also readily oxidized
      [(14)C]betainal to betaine (20-100 nmol/mg of chlorophyll per hr). Light
      increased the oxidation of both [(14)C]choline and [(14)C]betainal by isolated
      chloroplasts approximately 3-fold; this light-stimulation was abolished by 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (DCMU). Similar results were obtained with
      another chenopod (Beta vulgaris) but not with pea (Pisum sativum), a species that
      accumulates no betaine. The chloroplast site for betaine synthesis in chenopods
      contrasts with the mitochondrial site in mammals.

PMID- 16593570
TI  - Nitrate storage and retrieval in Beta vulgaris: Effects of nitrate and chloride
      on proton gradients in tonoplast vesicles.
AB  - The fluorescent probes acridine orange and oxonol-V were used as indicators of pH
      gradients (DeltapH) and membrane potential differences (DeltaPsi), respectively,
      in membrane vesicles believed to be derived from the tonoplast of Beta vulgaris
      L. Low concentrations of nitrate (1-5 mM) caused a partial dissipation of both
      DeltapH and DeltaPsi at vesicle transport sites distinct from the H(+)-ATPase. In
      contrast, chloride dissipated only DeltaPsi. A model is proposed in which nitrate
      and chloride enter the plant cell vacuole in response to a potential generated by
      the tonoplast H(+)-ATPase. Nitrate but not chloride may then be retrieved for
      metabolic use by the operation of a nitrate/proton symport at the tonoplast.

PMID- 16593571
TI  - Larval settlement rate: A leading determinant of structure in an ecological
      community of the marine intertidal zone.
AB  - Field studies demonstrate that the population structure of the barnacle Balanus
      glandula differs between locations of high and low larval settlement rate. These
      observations, together with results from a model for the demography of an open,
      space-limited population, suggest that the settlement rate may be a more
      important determinant of rocky intertidal community structure than is presently
      realized. Locations with a low larval settlement rate exhibit a generally low
      abundance of barnacles that varies slightly within years and greatly between
      years, reflecting yearly differences in settlement. Locations with a high
      settlement rate exhibit a generally high abudance of barnacles. However, the
      abundance varies greatly within years with a significant oscillatory component
      (period, 30 weeks) and only slightly between years regardless of yearly
      differences in settlement. At the low-settlement location mortality of barnacles
      is independent of the area occupied by barnacles. At the high-settlement location
      mortality is cover-dependent due to increased predation by starfish on areas of
      high barnacle cover. In both locations the cover-independent component of
      mortality does not vary with age during the first 60 weeks. As assumed in the
      demographic model, the kinetics of larval settlement can be described as a
      process in which the rate of settlement to a quadrat is proportional to the
      fraction of vacant space within the quadrat. Generalizations that the highest
      species diversity in a rocky intertidal community is found at locations of
      intermediate disturbance, and that competition causes zonation between species of
      the barnacle genera Balanus and Chthamalus, seem to apply only to locations with
      high-settlement rates.

PMID- 16593572
TI  - DNA sequence and transcript mapping of a soybean gene encoding a small heat shock
      protein.
AB  - The DNA sequence of a gene (Gmhsp17.5-E) encoding a small heat shock protein of
      soybean, Glycine max, has been determined. Nuclease S1 mapping of the 5' terminus
      of the corresponding RNA indicates that the start site for transcription is
      located 82 bases upstream from the coding region and 24 bases downstream from a
      "TATA"-like region (-T-T-T-A-A-A-T-A-). The 5' flanking region of Gmhsp17.5-E
      contains two imperfect dyads that closely resemble regulatory elements present in
      the promoters of heat-inducible genes of Drosophila. One, positioned 18 bases
      upstream from the TATA-like region, shows 90% homology to the Drosophila heat
      shock consensus sequence. The other overlaps an upstream TATA sequence and is
      located at position -213. Analysis of the derived amino acid sequence indicates
      that the protein encoded by Gmhsp17.5-E is related structurally to the four small
      heat shock proteins of Drosophila. This relationship is most evident by
      comparison of hydropathy profiles; they show conservation of several major
      hydrophilic and hydrophobic regions, which suggests that these proteins have
      common structural features.

PMID- 16593573
TI  - Site-specific DNA inversion is enhanced by a DNA sequence element in cis.
AB  - A segment of the bacteriophage P1 genome, called the C segment, can be inverted
      by site-specific recombination; the two different orientations of the invertible
      segment confer different host ranges to the phage. Inversion is catalyzed by the
      product of the cin gene which is adjacent to one of the crossover sites flanking
      the C segment. The Cin-catalyzed recombination can be measured in trans by using
      tester plasmids in which inversion switches on antibiotic-resistance genes. We
      show here that an additional sequence, distinct from the two crossover sites, is
      needed in cis for efficient inversion. This sequence is part of the cin
      structural gene and stimulates recombination more than 100-fold. We have
      localized the major enhancer sequence on a 72-base-pair fragment and found its
      activity to be largely independent of the orientation or position of the sequence
      with respect to the crossover sites.

PMID- 16593574
TI  - Sequence determination of the capsid protein gene and flanking regions of tobacco
      etch virus: Evidence for synthesis and processing of a polyprotein in potyvirus
      genome expression.
AB  - The nucleotide sequence of the 3'-terminal portion of the tobacco etch virus
      (TEV) genome was determined. The 2324-nucleotide sequence represented
      approximately one-fourth of the TEV genome and included the capsid protein gene
      and flanking regions. An open reading frame of 2135 nucleotides and an
      untranslated region of 189 nucleotides adjacent to a polyadenylate tract were
      identified. The sequence began within an open reading frame, indicating that the
      initiation codon was upstream of the available sequence data. The sequence of the
      20 NH(2)-terminal amino acids of the TEV capsid protein was established
      chemically. An identical amino acid sequence, predicted from the nucleotide
      sequence, was located, commencing at amino acid - 263. These data indicated that
      maturation of the capsid protein required a post-translational cleavage of a
      larger protein precursor, with a probable cleavage site between the amino acids
      glutamine and glycine.

PMID- 16593575
TI  - Unidirectional circulation in a prebiotic photochemical cycle.
AB  - In this brief note, we suggest the possibility that a soliton-assisted
      unidirectional photochemical cycle has played a role in prebiotic evolution. This
      suggestion is based on a model calculation which is itself based on the detection
      of Davydov-type soliton overtones in acetanilide.

PMID- 16593576
TI  - Nodulin-24 gene of soybean codes for a peptide of the peribacteroid membrane and
      was generated by tandem duplication of a sequence resembling an insertion
      element.
AB  - A nodulin gene coding for a polypeptide with an apparent M(r) of 24,000 (nodulin
      24) was isolated from soybean (Glycine max). DNA sequence analysis of this gene
      revealed that its coding capacity is for a polypeptide of only M(r) 15,100 and is
      interrupted by four introns. The three middle exons and their flanking segments
      appear to have been generated by duplications of a unit resembling an insertion
      sequence. This unit is bounded by a 12-base-pair inverted repeat and encompasses
      the 54-base-pair exon corresponding to each of three central hydrophobic domains
      of the protein, nodulin-24. The resulting repeated hydrophobic structure of this
      protein may be responsible for an apparent increase in M(r) from 15,100 to
      24,000. In vitro translation and immunological studies suggest that nodulin-24 is
      a precursor and is processed cotranslationally into a M(r) 20,000 polypeptide.
      This polypeptide is a component of the membrane envelope enclosing the bacteroids
      (peribacteroid membrane) synthesized during symbiosis with Rhizobium. The low
      degree (<6%) of sequence divergence among the repeated units suggests that this
      gene has been generated recently during the evolution of symbiotic nitrogen
      fixation in soybean.

PMID- 16593577
TI  - Isolation and properties of soybean [Glycine max (L.) Merr.] mutants that
      nodulate in the presence of high nitrate concentrations.
AB  - Soybean seeds [Glycine max (L.) Merr. ev. Bragg] were mutagenized with ethyl
      methanesulfonate. The M(2) progeny (i.e., the first generation after mutagenesis)
      of these seeds were screened for increased nodulation under high nitrate culture
      conditions. Fifteen independent nitrate-tolerant symbiotic (nts) mutants were
      obtained from 2500 M(2) families. In culture on sand with KNO(3), nodule mass and
      nodule number in mutant lines were several-fold those of the wild type cultured
      under the same conditions. Inheritance of the nts character through to subsequent
      generations was observed in the 10 mutants tested. Mutant nts382 also nodulated
      more than the wild type in the absence of nitrate. Furthermore, nitrate
      stimulated growth in both the wild type and nts382, and these lines had similar
      nitrate reductase activity. These results indicate that nts382 is affected in a
      nodule-development regulatory gene and not in a gene related to nitrate
      assimilation.

PMID- 16593578
TI  - Cloning and expression of cDNA for salmon growth hormone in Escherichia coli.
AB  - cDNA clones encoding chum salmon (Oncorhynchus keta) growth hormone (sGH) have
      been isolated from a cDNA library prepared from chum salmon pituitary gland
      poly(A)(+) RNA. Synthetic oligodeoxynucleotide mixtures based on amino acid
      residues 23-28 of sGH were used as hybridization probes to select recombinant
      plasmids carrying the sGH coding sequence. The complete nucleotide sequence of
      sGH cDNA has been determined. The cDNA sequence codes for a polypeptide of 210
      amino acids, including a putative signal sequence of 22 amino acids. The 5' and
      3' untranslated regions of the message were 64 and 426 bases long, respectively.
      Mature sGH was efficiently expressed in Escherichia coli carrying a plasmid in
      which the sGH cDNA was under control of the E. coli trp promoter; sGH comprised
      about 15% of the total cellular protein in such bacteria. The partially purified
      sGH from E. coli stimulated the growth of rainbow trout and the activity was
      indistinguishable from that of natural sGH.

PMID- 16593579
TI  - Isolation and characterization of cDNA clones for carrot extensin and a proline
      rich 33-kDa protein.
AB  - Extensins are hydroxyproline-rich glycoproteins associated with most
      dicotyledonous plant cell walls. To isolate cDNA clones encoding extensin, we
      started by isolating poly(A)(+) RNA from carrot root tissue, and then translating
      the RNA in vitro, in the presence of tritiated leucine or proline. A 33-kDa
      peptide was identified in the translation products as a putative extensin
      precursor because: (i) it is rich in proline and poor in leucine, and (ii) the
      message appears to be more abundant when carrot tissue is wounded. From a cDNA
      library constructed with poly(A)(+) RNA from wounded carrots, one cDNA clone
      (pDC5) was identified that specifically hybridized to poly(A)(+) RNA encoding
      this 33-kDa peptide. We isolated three cDNA clones (pDC11, pDC12, and pDC16) from
      another cDNA library using pDC5 as a probe. DNA sequence data, RNA hybridization
      analysis, and hybrid released in vitro translation indicate that the cDNA clone
      pDC11 encodes extensin and that cDNA clones pDC12 and pDC16 encode the 33-kDa
      peptide, which as yet has an unknown identity and function. The assumption that
      the 33-kDa peptide was an extensin precursor was invalid. RNA hybridization and
      DNA sequence analysis indicate that pDC5 is a hybrid clone corresponding to two
      RNA species. RNA hybridization analysis showed that RNA encoded by both clone
      types is accumulated upon wounding.

PMID- 16593580
TI  - ATP-dependent bioluminescence in the firefly squid, Watasenia scintillans.
AB  - The Japanese firefly squid, Watasenia scintillans, emits intense flashes of light
      from three tiny luminous organs that are located at the tip of each of a pair of
      ventral arms. Light is also produced from hundreds of other minute organs that
      are scattered over the body. The luminescence is due to an ATP-dependent
      reaction, with an optimal pH of 8.80. The decay of light intensity follows first
      order kinetics and the decay constant is independent of initial ATP
      concentration. The light emission also requires MgCl(2), a soluble component, and
      an insoluble component that is membrane bound. Squids represent a major group of
      organisms unrelated to fireflies in which ATP is required for bioluminescence.

PMID- 16593581
TI  - Group translocation as a mechanism for sucrose transfer into vacuoles from
      sugarcane cells.
AB  - Isolated vacuoles from sugarcane cells took up uridine diphosphate glucose (UDP
      Glc) from the surrounding medium at a rapid rate. After a 7-min incubation of
      vacuoles with UDP-[14C]Glc, sucrose and sucrose phosphate were identified in the
      vacuole extract. UDP-Glc in the incubation medium was converted to hexose
      phosphates, sucrose, and glucose, with very little UDP-Glc remaining. Fructose 6
      phosphate was not required for UDP-Glc uptake nor was [(14)C]fructose 6-phosphate
      taken up even in the presence of UDP-Glc. Glucose 6-phosphate and glucose 1
      phosphate also were not taken up into vacuoles. UDP-Glc uptake showed saturation
      kinetics with a K(m) of 0.7 mM and a V(max) of 11.1 nmol/min per 10(6) vacuoles.
      The optimum pH for UDP-Glc uptake was between 6.5 and 7.0. Uptake of UDP-Glc
      could be inhibited by p-chloromercuriphenylsulfonic acid, UDP, and GDP, and to a
      lesser extent by carbonyl cyanide m-chlorophenylhydrazone. The UDP-Glc binding
      site was specific for UDP-Glc; adenosine diphosphate glucose was not taken up,
      and guanosine diphosphate glucose did not compete with UDP-Glc for the binding
      site. The results suggest that sucrose transfer into vacuoles from sugarcane is
      via a group translocation mechanism, probably involving five tonoplast-bound
      enzymes.

PMID- 16593582
TI  - Flower petal microtexture is a tactile cue for bees.
AB  - Honeybees are shown to be able to detect, learn, and discriminate between
      microsculptured epidermes of flower petals. The sensilla trichodea at the tips of
      the bees' antennae are in the same size range as the microsculptural features of
      the petals (ca. 10 mum), which presumably deflect these mechanoreceptive sensilla
      in characteristic ways. Honeybees were trained to associate reward with one
      floral texture and to choose that over another. Further, the bees also recognized
      differences in textures at different ends of petals of the same species. The
      phenomenon is significant in that it suggests another way in which insect
      pollinators can discriminate between the flowers of different plant species and
      so act as species isolators. Also, the microsculptural patterns differ from one
      end of a petal to the other and, therefore, can be used as nectar-guides by
      foraging bees. This study presents a previously unreported conditioned response
      to texture by insects and shows the functional significance of a floral character
      used in plant taxonomy.

PMID- 16593583
TI  - Geometry and topology of isoparametric submanifolds in euclidean spaces.
AB  - Restrictions are given on the possible marked Dynkin diagrams of isoparametric
      submanifolds, and their homology and cohomology are computed by an extension of
      the techniques used by Bott and Samelson [Bott, R. & Samelson, H. (1958) Am. J.
      Math. 80, 964-1029] and by Borel [Borel, A. (1953) Ann. Math. 57 (2), 115-207]
      for G/T.

PMID- 16593584
TI  - Linkage and homology analysis divides the eight genes for the small subunit of
      petunia ribulose 1,5-bisphosphate carboxylase into three gene families.
AB  - Twenty-six lambda phage clones with homology to coding sequences of the small
      subunit (SSU) of ribulose 1,5-bisphosphate carboxylase have been isolated from an
      EMBL3 lambda phage bank of Petunia (Mitchell) DNA. Restriction mapping of the
      phage inserts shows that the clones were obtained from five nonoverlapping
      regions of petunia DNA that carry seven SSU genes. Comparison of the HindIII
      genomic fragments of petunia DNA with the HindIII restriction fragments of the
      isolated phage indicates that petunia nuclear DNA encodes eight SSU genes, seven
      of which are present in the phage clones. Two incomplete genes, which contain
      only the 3' end of an SSU gene, were also found in the phage clones. We
      demonstrate that the eight SSU genes of petunia can be divided into three gene
      families based on homology to three petunia cDNA clones. Two gene families
      contain single SSU genes and the third contains six genes, four of which are
      closely linked within petunia nuclear DNA.

PMID- 16593585
TI  - Primary structure of the soybean nodulin-35 gene encoding uricase II localized in
      the peroxisomes of uninfected cells of nodules.
AB  - Nodulin-35 (N-35), a subunit of nodule-specific uricase (uricase II) of soybean
      (Glycine max), is shown to be preferentially synthesized on free polysomes during
      nodule development and is localized in peroxisomes of the uninfected cells of
      this tissue. A cDNA clone, isolated by using mRNA from immunoprecipitated
      polysomes, revealed the primary structure of this protein with a molecular mass
      of 35,100. That this clone represents N-35 was confirmed by comparing the deduced
      amino acid sequence with the partial sequence of a CNBr-cleaved peptide of
      purified N-35. Southern blot hybridizations with genomic DNA suggest that there
      are several EcoRI fragments containing N-35 sequences. Three of these sequences
      were isolated from a genomic library of soybean. Nucleotide sequence analysis
      showed that the complete gene extends almost 5000 base pairs on two EcoRI
      fragments and the coding region (309 codons) is interrupted by seven introns
      ranging in size from 154 to 1341 base pairs. Lack of a signal sequence and its
      translation on free polysomes suggest that N-35 is posttranslationally
      transported to the peroxisomes. Furthermore, there is no cross-hybridization of N
      35 cDNA with RNA from young (3- to 4-day) roots and leaves, indicating that the
      observed "uricase" activity in these tissues is due to the product of a different
      gene.

PMID- 16593586
TI  - Inheritance, organization, and mapping of rbcS and cab multigene families in pea.
AB  - DNA restriction endonuclease fragment patterns corresponding to both the rbcS and
      cab multigene families of pea are each shown to segregate as single Mendelian
      units in the F(2) progeny of two separate crosses. All of the observed variation
      in each of the multigene families is thus organized on the chromosome in a
      tightly linked complex. Linkage relationships between both multigene families and
      an array of morphological and isozyme markers establish the location of the rbcS
      and cab gene clusters on pea chromosomes 5 and 2, respectively. Our results,
      which indicate a high level of DNA restriction fragment length polymorphism in
      pea, suggest sufficient variation to permit the construction of a highly detailed
      linkage map.

PMID- 16593587
TI  - Gametophytic self-incompatibility is controlled by a single major locus on
      chromosome 1 in Lycopersicon peruvianum.
AB  - By using a number of previously mapped enzyme-coding genes as genetic markers, it
      has been possible to scan the genome of Lycopersicon peruvianum for gene(s)
      controlling the gametophytic self-incompatibility reaction. Regardless of genetic
      background or level of inbreeding, only a single locus (S), mapping to chromosome
      1, was found to control the self-incompatibility reaction. Despite the widespread
      occurrence of this form of self-incompatibility in higher plants, to the best of
      our knowledge, the locus underlying the response has not been confirmed
      previously through genetic mapping, and the results cast doubts on hypotheses
      requiring multifactoral or dynamic control of gametophytic self-incompatibility.

PMID- 16593588
TI  - Constants and pseudo-constants of the Kadomtsev-Petviashvili equation.
AB  - Elucidating earlier work, it is shown that the Kadomtsev-Petviashvili equation
      has n + 2 constants for all n >/= 0. It also has a pseudo-constant from which the
      constants can be obtained by differentiation with respect to time. The pseudo
      constant can be obtained from a basis functional J(n) ((n+2)) = -1/18 [unk]
      y(n+2)q by taking repeated Poisson brackets with the Hamiltonian.

PMID- 16593589
TI  - Characterization of a pigment-dispersing hormone in eyestalks of the fiddler crab
      Uca pugilator.
AB  - A pigment-dispersing hormone (PDH) from eyestalks of the fiddler crab Uca
      pugilator has been purified by gel filtration, ion-exchange chromatography,
      partition chromatography, and reversed-phase liquid chromatography. Based on
      automated gas-phase sequencing and subsequent identification of carboxyl-terminal
      amide, we have assigned the primary structure of this peptide as Asn-Ser-Glu-Leu
      Ile-Asn-Ser-Ile-Leu-Gly-Leu-Pro-Lys-Val-Met-Asn-Asp-Ala-NH (2). We have confirmed
      the sequence by synthesizing this peptide and demonstrating that the synthetic
      PDH and the native PDH display identical chromatographic behavior and biological
      activity. This hormone is a member of a family of invertebrate neuropeptides that
      includes a light-adapting/pigment-dispersing octadecapeptide hormone from the
      prawn Pandalus borealis. In assays for melanophore pigment dispersion in
      destalked fiddler crabs, Uca PDH was 21-fold more potent than Pandalus PDH. These
      two hormones share a hexapeptide core sequence (residues 5-10: -Ile-Asn-Ser-Ile
      Leu-Gly-) as well as the amino- and carboxyl-terminal residues but differ at
      positions 3, 4, 11, 13, 16, and 17. These results point to speciesrelated or
      group-specific structural differences among crustacean PDHs.

PMID- 16593590
TI  - Chlorophyll biosynthesis and assembly into chlorophyll-protein complexes in
      isolated developing chloroplasts.
AB  - Isolated developing plastids from greening cucumber cotyledons or from
      photoperiodically grown pea seedlings incorporated (14)C-labeled 5-aminolevulinic
      acid (ALA) into chlorophyll (Chl). Incorporation was light dependent, enhanced by
      S-adenosylmethionine, and linear for 1 hr. The in vitro rate of Chl synthesis
      from ALA was comparable to the in vivo rate of Chl accumulation. Levulinic acid
      and dioxoheptanoic acid strongly inhibited Chl synthesis but not plastid protein
      synthesis. Neither chloramphenicol nor spectinomycin affected Chl synthesis,
      although protein synthesis was strongly inhibited. Components of thylakoid
      membranes from plastids incubated with [(14)C]ALA were resolved by
      electrophoresis and then subjected to autoradiography. This work showed that (i)
      newly synthesized Chl was assembled into Chl-protein complexes and (ii) the
      inhibition of protein synthesis during the incubation did not alter the labeling
      pattern. Thus, there was no observable short-term coregulation between Chl
      synthesis (from ALA) and the synthesis of membrane proteins in isolated plastids.

PMID- 16593591
TI  - P-element distribution in Eurasian populations of Drosophila melanogaster: A
      genetic and molecular analysis.
AB  - Genetic and molecular investigations were carried out with Eurasian Drosophila
      melanogaster populations on the P-M system of hybrid dysgenesis. In 27 strains
      sampled from France to Middle Asia, a clear gradient exists between Western
      Europe, in which most modern strains are of the Q type, and eastern areas, in
      which M-cytotype strains predominate. Molecular analysis on individual flies was
      performed with two complementary probes of the cloned 2.9-kilobase P element. The
      results provide evidence for a gradually decreasing frequency of P elements from
      west to east, but the presence of P-homologous sequences has been ascertained in
      all of the wild M-cytotype populations analyzed. Moreover, some active P elements
      with GD sterility potential were revealed in the majority of M-cytotype
      populations when tested with a highly sensitive reference line. The gradual
      change in distribution of the polymorphic P family in Eurasia is discussed in
      relation to the structure of the elements together with the theories of P-M
      evolution and is interpreted as the present invasion of Eurasian populations by
      these elements.

PMID- 16593592
TI  - Nonsense mutations in the Chlamydomonas chloroplast gene that codes for the large
      subunit of ribulosebisphosphate carboxylase/oxygenase.
AB  - The Chlamydomonas reinhardtii chloroplast mutants 18-5B and 18-7G lack both the
      chloroplast-encoded large subunit and nuclear-encoded small subunit of the
      chloroplast enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39).
      A chloroplast intergenic-suppression model has been postulated to account for the
      genetic instability of 18-5B revertants. Here, we have determined the molecular
      basis of the 18-5B and 18-7G mutants. They contain nonsense mutations close to
      the 3' and 5' ends of their large-subunit genes, respectively. Pulse-chase
      experiments revealed that the 18-5B mutant produces a truncated large subunit
      that is unstable. In connection with previous experiments, this work identifies
      nonsense suppression in the chloroplast. Small subunits are also synthesized but
      then degraded in the mutants. Thus, the coordinated absence of subunits is
      achieved through degradation of the small subunit in the specific absence of the
      large subunit.

PMID- 16593593
TI  - Probabilistic aspects of finite-fuel stochastic control.
AB  - The problem is that of following the Brownian path by a nondecreasing, bounded
      process in such a way as to minimize the expected cost over a finite horizon.
      Using purely probabilistic arguments, one obtains a fairly explicit
      representation for the value of this problem, as well as information about the
      nature of the optimal process.

PMID- 16593594
TI  - Outlining social physics for modern societies-locating culture, economics, and
      politics: The Enlightenment reconsidered.
AB  - A groundwork is laid for a formulation of the modern human social system as a
      field continuum. As in a simple material physical field, the independent implied
      relationships of materials or processes in flux have to be based on local
      conservations of mass, energy, and momentum. In complex fields, the transport
      fluctuations of momentum are transformed into action modes (e.g., [unk] pdq =
      SigmaH(i) = H, a characteristic quantum of action over a characteristic cycle
      time). In complex living systems, a fourth local conservation of population
      number, the demographic variable, has to be added as a renormalized variable.
      Modern man, settled in place via agriculture, urbanized, and engaged largely in
      trade and war, invents a fifth local conservation-value-in-trade, the economic
      variable. The potentials that drive these five fluxes are also enumerated. Among
      the more evident external and internal physical-chemical potentials, the driving
      potentials include a sheaf of internal potential-like components that represent
      the command-control system emergent as politics. In toto, culture represents the
      social solvent with the main processes of economics and politics being driven by
      a social pressure.

PMID- 16593595
TI  - Light regulation of the synthesis of the large subunit of ribulose-1,5
      bisphosphate carboxylase in peas: Evidence for translational control.
AB  - The specific activity of ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39)
      increases 30- to 50-fold when dark-grown pea seedlings are shifted into the
      light. The large subunit (LS) of this multimeric protein is known to be
      synthesized in the chloroplast, but plastids from dark-grown cells contain
      relatively low levels of LS. However, despite the low level of LS synthesis in
      the plastids of dark-grown plants, these organelles contain significant levels of
      LS mRNA. Hybridization studies showed that the amount of LS mRNA increased about
      3-fold, relative to total plant RNA, when dark-grown plants were illuminated.
      This increase in LS mRNA can be accounted for by a similar increase in
      chloroplast genome copy number. It was found that the amount of translatable LS
      mRNA per mug of plastid RNA is similar when isolated from either dark-grown
      plants or dark-grown plants subjected to light. These results suggest that
      although light can increase the level of LS mRNA by increasing the copy number of
      this gene, the primary regulation of LS synthesis by light in pea chloroplasts is
      at the level of translation.

PMID- 16593596
TI  - Azotobacter vinelandii nifD- and nifE-encoded polypeptides share structural
      homology.
AB  - The Azotobacter vinelandii nifE gene was isolated and its complete nucleotide
      sequence was determined. The amino acid sequences deduced from the A. vinelandii
      nifE and nifD gene sequences were compared and found to share striking primary
      sequence homology. This homology implies a functional and possibly an
      evolutionary relationship between these two gene products. The structural
      homology is discussed with regard to the potential FeMo cofactor binding
      properties of these polypeptides and the possible role of a nifEN product complex
      as a surrogate MoFe protein.

PMID- 16593597
TI  - mRNA stabilization controls the expression of a class of developmentally
      regulated genes in Dictyostelium discoideum.
AB  - During the development of Dictyostelium discoideum, several thousand new mRNA
      species appear in the cytoplasm after the cells have formed stable aggregates.
      Here we show that six of these late mRNAs, corresponding to six clones randomly
      chosen from a genomic library, are synthesized from the very beginning of
      development at a rate comparable to that observed late in development but that
      transcripts do not accumulate until after aggregation. The early- and late
      synthesized mRNAs are identical in size and compete with each other for
      hybridization to the genomic clones. The early-synthesized mRNAs do not
      accumulate in the cytoplasm in the preaggregation stage because they are very
      unstable. Their stability, estimated from the kinetics of incorporation during
      continuous labeling with (32)P, increases by perhaps an order of magnitude in the
      postaggregation stage. We conclude that mRNA stabilization is the major
      controlling factor of the expression of these genes.

PMID- 16593598
TI  - F1 and F2: Two similar genes regulated differently during development of
      Drosophila melanogaster.
AB  - Screening a cDNA library of 2- to 3-day-old flies with poly(A)(+) RNA from male
      and female flies, we were able to isolate a small number of clones hybridizing
      preferentially with RNA from female flies. Four cDNA clones, derived from a
      single mRNA species, proved to be highly abundant in female flies. When we
      screened a genomic library with the longest cDNA, we obtained two genomic clones,
      F1 and F2; F1 was a direct copy of the cDNA and F2 was obtained by cross
      hybridization. A detailed analysis of these genomic clones revealed two
      independent genes coding for proteins of 50 kDa that are >90% homologous. RNA
      analysis with gene-specific probes from the 3' untranslated region showed an
      expression of F1 in all stages of development with a 5- to 10-fold overexpression
      of this RNA in female flies compared with males. In contrast to F1, F2 is mainly
      expressed in late pupae and is expressed only at low levels in adult flies.

PMID- 16593599
TI  - Pellet microfossils: Possible evidence for metazoan life in Early Proterozoic
      time.
AB  - Microfossils resembling fecal pellets occur in acid-resistant residues and thin
      sections of Middle Cambrian to Early Proterozoic shale. The cylindrical
      microfossils average 50 x 110 mum and are the size and shape of fecal pellets
      produced by microscopic animals today. Pellets occur in dark gray and black rocks
      that were deposited in the facies that also preserves sulfide minerals and that
      represent environments analogous to those that preserve fecal pellets today.
      Rocks containing pellets and algal microfossils range in age from 0.53 to 1.9
      gigayears (Gyr) and include Burgess Shale, Greyson and Newland Formations, Rove
      Formation, and Gunflint Iron-Formation. Similar rock types of Archean age,
      ranging from 2.68 to 3.8 Gyr, were barren of pellets. If the Proterozoic
      microfossils are fossilized fecal pellets, they provide evidence of metazoan life
      and a complex food chain at 1.9 Gyr ago. This occurrence predates macroscopic
      metazoan body fossils in the Ediacaran System at 0.67 Gyr, animal trace fossils
      from 0.9 to 1.3 Gyr, and fossils of unicellular eukaryotic plankton at 1.4 Gyr.

PMID- 16593600
TI  - Conservation of nodulation genes between Rhizobium meliloti and a slow-growing
      Rhizobium strain that nodulates a nonlegume host.
AB  - Parasponia, a woody member of the elm family, is the only nonlegume genus whose
      members are known to form an effective nitrogen-fixing symbiosis with a Rhizobium
      species. The bacterial strain RP501 is a slow-growing strain of Rhizobium
      isolated from Parasponia nodules. Strain RP501 also nodulates the legumes siratro
      (Macroptilium atropurpureum) and cowpea (Vigna unguiculata). Using a cosmid clone
      bank of RP501 DNA, we isolated a 13.4-kilobase (kb) EcoRI fragment that
      complemented insertion and point mutations in three contiguous nodulation genes
      (nodABC) of Rhizobium meliloti, the endosymbiont of alfalfa (Medicago sativa).
      The complemented R. meliloti nod mutants induced effective nitrogen-fixing
      nodules on alfalfa seedlings but not on siratro, cowpeas, or Parasponia. The
      cloned RP501 nodulation locus hybridized to DNA fragments carrying the R.
      meliloti nodABC genes. A 3-kb cluster of Tn5 insertion mutations on the RP501
      13.4-kb EcoRI fragment prevented complementation of R. meliloti nodABC mutations.

PMID- 16593601
TI  - Auditory representation of autogenous song in the song system of white-crowned
      sparrows.
AB  - The HVc (hyperstriatum ventrale, pars caudale) is a forebrain nucleus in the
      motor pathway for the control of song. Neurons in the HVc also exhibit auditory
      responses. A subset of these auditory neurons in the white-crowned sparrow
      (Zonotrichia leucophrys) have been shown to be highly selective for the
      individual bird's own (autogenous) song. By using multiunit recording techniques
      to sample from a large population, we demonstrate that the entire population of
      auditory neurons in the HVc is selective for autogenous song. The selectivity of
      these neurons must reflect the song-learning process, for the acoustic parameters
      of a sparrow's song are acquired by learning. By testing with laboratory-reared
      birds, we show that HVc auditory neurons prefer autogenous song over the tutor
      model to which the birds were exposed early in life. Thus, these neurons must be
      specified at or after the time song crystallizes. Since song is learned by
      reference to auditory feedback, HVc auditory neurons may guide the development of
      the motor program for song. The maintenance of a precise auditory representation
      of autogenous song into adulthood can contribute to the ability to distinguish
      the fine differences among conspecific songs.

PMID- 16593602
TI  - Acyl-acyl carrier protein as a source of fatty acids for bacterial
      bioluminescence.
AB  - Pulse-chase experiments with [(3)H]tetradecanoic acid and ATP showed that the
      bioluminescence-related 32-kDa acyltransferase from Vibrio harveyi can
      specifically catalyze the deacylation of a (3)H-labeled 18-kDa protein observed
      in extracts of this bacterium. The 18-kDa protein has been partially purified and
      its physical and chemical properties strongly indicate that it is fatty acyl-acyl
      carrier protein (acyl-ACP). Both this V. harveyi [(3)H]acylprotein and
      [(3)H]palmitoyl-ACP from Escherichia coli were substrates in vitro for either the
      V. harveyi 32-kDa acyltransferase or the analogous enzyme ("34K") from
      Photobacterium phosphoreum. TLC analysis indicated that the hexane-soluble
      product of the reaction is fatty acid. Phosphate ions and, to a lesser extent,
      organic alcohols stimulated the rate of acyl-protein cleavage. No significant
      cleavage of either E. coli or V. harveyi tetradecanoyl-ACP was observed in
      extracts of these bacteria unless the 32-kDa or 34K acyltransferase was present.
      Since these enzymes are believed to be responsible for the supply of fatty acids
      for reduction to form the aldehyde substrate of luciferase, the above results
      suggest that long-chain acyl-ACP is the source of fatty acids for
      bioluminescence.

PMID- 16593603
TI  - Molecular mechanism of water oxidation in photosynthesis based on the functioning
      of manganese in two different environments.
AB  - We present a model of photosynthetic water oxidation that utilizes the property
      of higher-valent Mn ions in two different environments and the characteristic
      function of redox-active ligands to explain all known aspects of electron
      transfer from H(2)O to Z, the electron donor to P680, the photosystem II reaction
      center chlorophyll a. There are two major features of this model. (i) The four
      functional Mn atoms are divided into two groups of two Mn each: [Mn] complexes in
      a hydrophobic cavity in the intrinsic 34-kDa protein; and (Mn) complexes on the
      hydrophilic surface of the extrinsic 33-kDa protein. The oxidation of H(2)O is
      carried out by two [Mn] complexes, and the protons are transferred from a [Mn]
      complex to a (Mn) complex along the hydrogen bond between their respective ligand
      H(2)O molecules. (ii) Each of the two [Mn] ions binds one redox-active ligand
      (RAL), such as a quinone (alternatively, an aromatic amino acid residue).
      Electron transfer occurs from the reduced RAL to the oxidized Z. When the
      experimental data concerning atomic structure of the water-oxidizing center
      (WOC), electron transfer between the WOC and Z, the electronic structure of the
      WOC, the proton-release pattern, and the effect of Cl(-) are compared with the
      predictions of the model, satisfactory qualitative and, in many instances,
      quantitative agreements are obtained. In particular, this model clarifies the
      origin of the observed absorption-difference spectra, which have the same pattern
      in all S-state transitions, and of the effect of Cl(-)-depletion on the S states.

PMID- 16593604
TI  - Mode of coaction between blue/UV light and light absorbed by phytochrome in light
      mediated anthocyanin formation in the milo (Sorghum vulgare Pers.) seedling.
AB  - Anthocyanin formation in milo (Sorghum vulgare Pers.) seedlings (coleoptile,
      mesocotyl, taproot) occurs only in white light and blue/UV light (BL/UV), while
      red light (RL) and far-RL are totally ineffective. However, after a BL/UV
      pretreatment, the participation of phytochrome can be demonstrated. With a short
      wavelength light source [peak emission in longwave UV (UV-A)], the mode of
      coaction between BL/UV and light absorbed by phytochrome (RL) was studied with
      the following principal results. (i) As soon as the seedling becomes competent to
      respond to UV-A (with regard to anthocyanin formation), the involvement of
      phytochrome can be detected. (ii) A 5-min pulse of UV-A has a strong effect on
      the anthocyanin synthesis in the milo mesocotyl. This effect is fully reversible
      if a long-wavelength far-RL pulse (RG9 light) is given immediately after the UV-A
      light pulse. (iii) When seedlings treated with 5 min of UV-A and 5 min of RG9
      light are kept in darkness for 3 hr and then transferred to RL, anthocyanin
      appears. (iv) In continuous UV-A treatment, anthocyanin accumulation starts after
      a lag phase of 3.5 hr (25 degrees C). A RL pretreatment prior to the onset of UV
      A treatment strongly increases anthocyanin accumulation in UV-A, though the lag
      phase is not affected. Moreover, a RL pretreatment does not affect the time
      course for escape from reversibility in UV-A. It is concluded from these data
      that BL/UV cannot mediate induction of anthocyanin synthesis in the absence of
      P(fr), the active form of phytochrome that absorbs maximally in the far-red.
      Rather, the action of BL/UV must be considered to establish responsiveness of the
      anthocyanin-producing mechanism to P(fr). P(fr) operates in this system via two
      different channels. As the effector of the terminal response, it sets in motion
      the signal-response chain that eventually leads to the appearance of anthocyanin.
      This is a slow process with a lag phase of the order of 3.5 hr. The second
      function of P(fr) is to determine the responsiveness to the effector P(fr) in
      mediating anthocyanin synthesis. This is a very fast and highly sensitive
      phytochrome action that can be detected readily within 1 min. However, as long as
      the plant has not received BL/UV, the strong effect of RL on the effectiveness of
      P(fr) remains cryptic. The effect of a RL pretreatment and the effect of a UV-A
      pretreatment on responsiveness towards P(fr) (or, effectiveness of P(fr)) were
      found to be totally independent of each other, even though it is the UV-A that
      permits operation of P(fr).

PMID- 16593605
TI  - Preferential fertilization in Plumbago: Ultrastructural evidence for gamete-level
      recognition in an angiosperm.
AB  - Gametic fusion patterns in the angiosperm Plumbago zeylanica were determined by
      using cytoplasmically dimorphic sperm cells differing in mitochondrion and
      plastid content and then identifying paternal organelles through their
      ultrastructural characteristics within the maternal cytoplasm at the time of
      fertilization. The virtual absence of plastids within the sperm cell that is
      physically associated with the vegetative nucleus allows paternal plastids to be
      used to trace the fate of the two male gametes after fusion. Such paternal
      plastids were present in the egg in >94% of the observed cases, indicating the
      preferential fusion of the plastid-rich, mitochondrion-poor sperm cell with the
      egg. In only one instance did the opposite pattern occur. Since the possibility
      of this result occurring as the consequence of chance in random fusions is <1 in
      7000, this represents strong evidence for the presence of a final putative
      recognition event occurring at the gametic level.

PMID- 16593606
TI  - Bird remains from an archaeological site on Henderson Island, South Pacific: Man
      caused extinctions on an "uninhabited" island.
AB  - Long thought never to have been inhabited and to be in a pristine ecological
      state, Henderson Island (southeast Pacific) is now known to have been colonized
      and then abandoned by Polynesians. Bones from an archaeological site on the
      island associated with (14)C dates of approximately 800 and approximately 500
      years B.P. include specimens of 12 species of birds, of which 3, a storm-petrel
      and two pigeons (Nesofregetta fuliginosa, Ducula cf. aurorae or D. pacifica, and
      Ducula cf. galeata), no longer occur on Henderson, and two others (Puffinus
      nativitatis and Sula sula) still visit but are not known to breed. The vanished
      species were presumably exterminated by Polynesians and the biota of Henderson
      Island can thus no longer be regarded as being in an unaltered state. The
      prehistoric abandonment of various small, unarable islands by Polynesians may
      have been due to the depletion of seabirds and pigeons, the only readily
      available food source. The species of pigeons identified from Henderson are known
      historically only from distant archipelagos and have never before been found
      sympatrically. Distributional patterns resulting from man-caused extinctions may
      give rise to erroneous interpretations of the relationships and evolutionary
      history of insular organisms. Certain endangered species, such as Ducula galeata,
      might effectively be preserved by reintroduction to abandoned islands that they
      occupied before human intervention.

PMID- 16593607
TI  - Structures of defective P transposable elements prevalent in natural Q and Q
      derived M strains of Drosophila melanogaster.
AB  - Several DNA sequences with homology to the complete 2.9-kilobase (kb) P element
      from a P strain in the United States were isolated and characterized from two
      Drosophila melanogaster strains collected on Chichi Jima, an island 1000 km south
      of Tokyo. Except for a missing central region and trivial unsequenced regions of
      38 base pairs, the 2.1-kb element isolated from a Q strain had the same DNA
      sequence as that of the complete P element. Seven other elements cloned from
      genomic DNAs of the Q strain and a Q-derived M strain all possessed the same
      restriction sites as those of the 2.9-kb P element except for one deleted region
      in each element. The finding of sequence conservation in P elements have had a
      common ancestor relatively recently. Thus, it is suggested that the P element
      family was a recent invader of the species. By contrast, no complete P element
      was found in these Japanese strains so far as surveyed, indicating the
      possibility that P elements in the Chichi Jima population are almost all
      defective. The implication of this possibility is discussed in relation to the
      uniqueness of the population on Chichi Jima where Q strains predominate and no P
      strains have yet been found.

PMID- 16593608
TI  - Brood care by male bumble bees.
AB  - Male Bombus griseocollis (Hymenoptera: Apidae) share in the brood care of
      nestmates by incubating pupae (usually during the first few days after they
      emerge as adults). Male posture during incubation of a pupa is identical to that
      observed for females. Pupae incubated by males were 4 degrees C-6 degrees C above
      the temperature of unincubated pupae. Although this increase was not as great as
      that caused by workers or queens, it was an important factor in warming pupae.
      Incubating males may benefit nestmates incidentally without lowering their own
      individual fitness.

PMID- 16593609
TI  - Gene expression of pigment-binding proteins of the bacterial photosynthetic
      apparatus: Transcription and assembly in the membrane of Rhodopseudomonas
      capsulata.
AB  - Lowering of oxygen partial pressure in chemotrophic cultures or reduction of
      light intensity in phototrophic cultures of Rhodopseudomonas capsulata induced
      formation of the photosynthetic apparatus. A maximum of mRNA coding for the
      reaction center (RC) and the light-harvesting 1 B870 antenna complex polypeptides
      occurred 30 min after induction. Maximal expression of mRNA for B800-B850 antenna
      proteins appeared with a lag time of about 25 min after RC/B870 mRNA. Pigment
      binding polypeptides were inserted into the membrane immediately after mRNA
      synthesis. It is concluded that the delayed formation of the B800-B850 complex
      compared to the RC and the B870 complex is caused by sequential expression of the
      corresponding genes. Biological activity of pigment-protein complexes increased
      after the incorporation of their polypeptides parallel to the maximum of
      bacteriochlorophyll synthesis. Studies on mutant strains defective in the
      formation of pigment-protein complexes suggested that pigment synthesis is of
      importance for assembly of stable complexes.

PMID- 16593610
TI  - Nucleotide sequences of the Pseudomonas savastanoi indoleacetic acid genes show
      homology with Agrobacterium tumefaciens T-DNA.
AB  - We report the nucleotide sequences of iaaM and iaaH, the genetic determinants
      for, respectively, tryptophan 2-monooxygenase and indoleacetamide hydrolase, the
      enzymes that catalyze the conversion of L-tryptophan to indoleacetic acid in the
      tumor-forming bacterium Pseudomonas syringae pv. savastanoi. The sequence
      analysis indicates that the iaaM locus contains an open reading frame encoding
      557 amino acids that would comprise a protein with a molecular weight of 61,783;
      the iaaH locus contains an open reading frame of 455 amino acids that would
      comprise a protein with a molecular weight of 48,515. Significant amino acid
      sequence homology was found between the predicted sequence of the tryptophan
      monooxygenase of P. savastanoi and the deduced product of the T-DNA tms-1 gene of
      the octopine-type plasmid pTiA6NC from Agrobacterium tumefaciens. Strong homology
      was found in the 25 amino acid sequence in the putative FAD-binding region of
      tryptophan monooxygenase. Homology was also found in the amino acid sequences
      representing the central regions of the putative products of iaaH and tms-2 T
      DNA. The results suggest a strong similarity in the pathways for indoleacetic
      acid synthesis encoded by genes in P. savastanoi and in A. tumefaciens T-DNA.

PMID- 16593611
TI  - Pathway of assembly of ribulosebisphosphate carboxylase/oxygenase from Anabaena
      7120 expressed in Escherichia coli.
AB  - We have placed the genes encoding ribulose-bisphosphate carboxylase/oxygenase
      from the Anabaena 7120 operon under transcriptional control of the lac promoter
      carried on the Escherichia coli plasmid pUC19. The genes encoding both the large
      and small subunit polypeptides (rbcL and rbcS) are transcribed and translated so
      that approximately 0.6% of the soluble protein in E. coli extracts is a fully
      functional holoenzyme with a sedimentation coefficient of approximately 18S,
      which contains stoichiometric amounts of the two subunits. However, expression of
      the large subunit polypeptide vastly exceeds that of the small subunit because
      the majority of transcripts terminate in the intergenic region between the rbcL
      and rbcS genes. As a result, excess large subunit is synthesized and accumulates
      in E. coli as an insoluble and catalytically inactive form. Because small subunit
      is found only in the high molecular weight soluble form of ribulosebisphosphate
      carboxylase/oxygenase, we propose that the small subunit promotes assembly of the
      hexadecameric form of the enzyme via heterodimers of large and small subunits.

PMID- 16593612
TI  - Accumulation of hydroxyproline-rich glycoprotein mRNAs in response to fungal
      elicitor and infection.
AB  - Hydroxyproline-rich glycoproteins (HRGPs) are important structural components of
      plant cell walls and also accumulate in response to infection as an apparent
      defense mechanism. Accumulation of HRGP mRNA in biologically stressed bean
      (Phaseolus vulgaris L.) cells was monitored by blot hybridization with (32)P
      labeled tomato genomic HRGP sequences. Elicitor treatment of suspension-cultured
      cells caused a marked increase in hybridizable HRGP mRNA. The response was less
      rapid but more prolonged than that observed for mRNAs encoding enzymes of
      phytoalexin biosynthesis. HRGP mRNA also accumulated during race:cultivar
      specific interactions between bean hypocotyls and the partially biotrophic fungus
      Colletotrichum lindemuthianum, the causal agent of anthracnose. In an
      incompatible interaction (host resistant) there was an early increase in HRGP
      mRNA correlated with expression of hypersensitive resistance; whereas, in a
      compatible interaction (host susceptible), marked accumulation of HRGP mRNA
      occurred as a delayed response at the onset of lesion formation. In both
      interactions, mRNA accumulation was observed in uninfected cells distant from the
      site of fungal inoculation, indicating intercellular transmission of an
      elicitation signal.

PMID- 16593613
TI  - Rapid transient induction of phenylalanine ammonia-lyase mRNA in elicitor-treated
      bean cells.
AB  - DNAs complementary to a size-selected fraction of poly(A)(+) RNA present in
      elicitor-treated cells of bean (Phaseolus vulgaris L.) were inserted into pAT153
      and used to transform Escherichia coli strain C600. Five clones were identified
      by hybrid-selected translation and cross-hybridization that contained sequences
      complementary to mRNA encoding phenylalanine ammonia-lyase (EC 4.3.1.5), which
      catalyzes the first reaction of phenylpropanoid biosynthesis. The longest insert
      contained a single open reading frame of 1520 base pairs together with 223 base
      pairs of 3' untranslated sequence. RNA blot hybridization showed that elicitor
      caused a rapid, marked but transient increase in phenylalanine ammonia-lyase mRNA
      that was closely correlated with changes in translatable mRNA activity in vitro
      and enzyme synthesis in vivo. Blot hybridization of newly synthesized mRNA
      purified by organomercurial affinity chromatography following in vivo pulse
      labeling with 4-thiouridine indicates that elicitor caused a rapid stimulation of
      phenylalanine ammonia-lyase mRNA synthesis as an early in the defense response
      leading to accumulation of phenylpropanoid-derived phytoalexins.

PMID- 16593614
TI  - Electron transfer-driven ATP synthesis in Methanococcus voltae is not dependent
      on a proton electrochemical gradient.
AB  - Intracellular ATP levels in whole cells of Methanococcus voltae respond to
      electron transfer coupled to methanogenesis. ATP synthesis can also be induced by
      an artificially imposed transmembrane electrical potential [formed by
      electrogenic movement outwards of potassium (induced by valinomycin) or of
      protons (induced by an uncoupler], or by a pH gradient (acid outside). These
      results implicate the existence of a reversible ATPase coupled to electrogenic
      movement of an ion(s) other than potassium or proton, and that ionophores are
      competent to catalyze ion movement across the cytoplasmic membrane of this
      organism (which is the sole membrane structure in this species). ATP synthesis
      driven by electron transfer is, however, insensitive to the addition of such
      ionophores. These results indicate that although cells possess an ion
      translocating ATPase (possibly involved in the maintenance of internal ionic
      composition homeostasis), methanogenesis-driven ATP synthesis does not involve
      the intermediacy of a transmembrane ion gradient. Primarily because methane
      formation has been previously demonstrated to involve true electron transfer,
      substrate-level phosphorylation (at least in analogy to other systems) has been
      generally ruled out. The results presented here suggest that at least one
      methanogenic bacterium may use a direct linkage of ATP synthesis to electron
      transfer.

PMID- 16593615
TI  - Effect of magnetic fields on the triplet state lifetime in photosynthetic
      reaction centers: Evidence for thermal repopulation of the initial radical pair.
AB  - The lifetime of the molecular triplet state formed by recombination of the
      radical ion pair in quinonedepleted bacterial photosynthetic reaction centers is
      found to depend on applied magnetic field strength. It is suggested that this
      magnetic field effect results from thermally activated repopulation of the same
      radical ion pair that generates the triplet. Consistent with this hypothesis, the
      magnetic field effect on the triplet lifetime disappears at low temperature where
      the triplet state decays exclusively by ordinary intersystem crossing. This
      activated pathway for the decay of the triplet state can explain the strong
      temperature dependence of the triplet decay rate. A detailed theoretical
      treatment of the problem within a set of physically reasonable assumptions
      relates the observed temperature dependence of the triplet decay rate to the
      energy gap between the radical ion pair intermediate and the triplet state. This
      energy gap is estimated to be about 950 cm(-1) (0.12 eV). Combined with an
      estimate of the energy of the donor excited state, we obtain an energy gap
      between the excited singlet state of the donor and the radical ion pair of 2,250
      cm(-1) (0.28 eV).

PMID- 16593616
TI  - Structure of glycolate oxidase from spinach.
AB  - A high-resolution structure determination of glycolate oxidase from spinach is
      reported. X-ray data were collected on films at the synchrotron radiation source
      in Daresbury, England. The structure was solved by using two heavy-atom
      derivatives and a solvent-flattening procedure developed by B.-C. Wang. The
      subunit structure is essentially a structure of the eight-stranded alpha/beta
      barrel type first described for triosephosphate isomerase. In addition, there are
      70 residues at the NH(2) terminus and 45 residues between strand four and helix
      four of the barrel, which are arranged in a helical domain outside the COOH end
      of the parallel strands of the barrel. The active site is in a cleft between
      these domains with the coenzyme FMN essentially bound to the barrel and a
      substrate analogue, thioglycolate, bound to the helical domain. The molecule is
      octameric with 422 symmetry and has a 15- to 20-A-wide hole in the middle.

PMID- 16593617
TI  - Excited states and primary photochemical reactions in the photosynthetic
      bacterium Heliobacterium chlorum.
AB  - The charge separation and excited states of antenna bacteriochlorophyll in
      membrane fragments of the recently discovered photosynthetic bacterium
      Heliobacterium chlorum were studied by absorbance-difference spectroscopy.
      Formation of singlet excited states of bacteriochlorophyll g with a lifetime of
      200 ps or less was observed as the disappearance of the ground state absorption
      bands. From the absorbance-difference spectra, it was concluded that the primary
      photochemical reaction consists of the transfer of an electron from the primary
      donor P-798 to a possibly bacteriochlorophyll c-like pigment absorbing at 670 nm.
      Electron transfer to the secondary acceptor occurred with a time constant of
      about 500 ps. The midpoint potential of this acceptor (between -450 and -560 mV)
      and the absence of significant absorbance changes in the near-infrared upon its
      reduction suggest that this acceptor is an iron-sulfur center. It is concluded
      that the primary photochemistry of H. chlorum is similar to that of green sulfur
      bacteria.

PMID- 16593618
TI  - Identification of a high molecular weight polypeptide that may be part of the
      circadian clockwork in Acetabularia.
AB  - In the chloroplast fraction of the unicellular and uninucleate green alga
      Acetabularia, we have detected a M(r) approximately 230,000 protein (p230) whose
      synthesis exhibits a pronounced endogenous diurnal rhythm. As judged by scanning
      densitometry of fluorographs of NaDodSO(4)/polyacrylamide gels, the synthesis of
      other proteins in the same fraction was independent of the time in the cycle. The
      incorporation of [(35)S]methionine into p230 was completely inhibited by
      cycloheximide, whereas chloramphenicol had no effect. This strongly suggests that
      p230 is translated on 80S ribosomes. Eighthour periods of exposure to
      cycloheximide produced a shift in the phase of the oscillation of p230 synthesis.
      The results are consistent with the hypothesis that p230 is essential for
      expression of circadian rhythms in Acetabularia.

PMID- 16593619
TI  - Interspecific chloroplast recombination in a Nicotiana somatic hybrid.
AB  - Genetic recombination between chloroplasts of two flowering plant species,
      Nicotiana tabacum and Nicotiana plumbaginifolia, after somatic cell fusion is
      described. The parental lines differed in three cytoplasmic genetic markers. The
      N. tabacum mutant SR1-A15 was streptomycin-resistant, defective in chloroplast
      greening, and lincomycin-sensitive. The N. plumbaginifolia mutant LR400 was
      streptomycin-sensitive, normal green, and lincomycin-resistant. Streptomycin
      resistant clones in cell culture are identified by their ability to form a green
      callus on a selective medium. Streptomycin resistance in the SR1-A15 mutant could
      not be expressed due to defective chloroplasts. Protoplasts of the two species
      were fused, and calli grown from the fused population were screened for the
      expression of streptomycin resistance from the SR1-A15 line as the result of
      interspecific chloroplast recombination. A somatic hybrid, pt14, expressed a new
      combination of the cytoplasmic genetic markers. In the pt14 chloroplast genome
      three N. tabacum and four N. plumbaginifolia parent specific restriction sites
      have been identified, indicating that the pt14 chloroplast genome contains at
      least six recombination sites.

PMID- 16593620
TI  - DNA amplification patterns in maize endosperm nuclei during kernel development.
AB  - Increased DNA levels in centrally located endosperm nuclei are shown to be
      related to endosperm development in Zea mays. Mitotic activity sharply decreases
      in endosperm cells 10-12 days after pollination. At this time nuclear size and
      DNA content per nucleus (where C = haploid content) sharply increase until peak
      levels are reached at about 14-18 days after pollination. Mean DNA content per
      endosperm nucleus in strain A188 was shown by Feulgen cytophotometry to increase
      to about 90C by this peak stage, with the pattern being remarkably consistent
      over four consecutive growing seasons. Some individual nuclei achieved levels of
      >200C. Most other strains compared during one growing season averaged even higher
      peak levels of DNA per nucleus than did A188. Individual nuclei in those strains
      reached levels as high as 690C. A decrease in DNA level was observed in older
      endosperms with most strains. Endosperm mutant strains did not show a significant
      reduction in DNA. Opaque-2 mutants in several backgrounds achieved higher levels
      of DNA per nucleus. DNA levels from F(1) endosperms did not indicate heterosis.
      Regardless of differences in DNA content, the pattern of DNA increasing as
      development proceeds followed by a DNA decrease was observed for most strains.
      Cytological studies reveal much variation in chromatin strandedness, a maximum of
      three nucleoli, a maximum of three nucleolar organizer regions, and approximately
      30 diffuse chromatin masses in older endosperm tissue. A form of DNA
      amplification, perhaps polytenization, appears to be occurring during endosperm
      development.

PMID- 16593621
TI  - Peptidergic modulation of patterned motor activity in identified neurons of
      Helisoma.
AB  - The neuroactive peptides SCP(B) (small cardioactive peptide B) and FMRFamide (Phe
      Met-Arg-Phe-NH(2)), both originally isolated from molluscs, have potent
      modulatory effects upon the production of patterned motor activity in identified
      neurons (e.g., B5 and B19) in the buccal ganglia of the snail Helisoma. Such
      patterned motor activity has previously been shown to underlie feeding behavior.
      Micromolar concentrations of SCP(B) initiate patterned motor activity in
      quiescent ganglia and increase the rate of activity in ganglia that are
      spontaneously active. Micromolar concentrations of FMRFamide inhibit patterned
      motor activity in Helisoma buccal ganglia, and 10 muM FMRFamide completely
      suppresses such activity. In addition, there are both anti-SCP(B)-and anti
      FMRFamide-immunoreactive neurons in Helisoma buccal ganglia. Our results suggest
      that peptides may play a prominent role in the regulation of feeding behavior in
      Helisoma.

PMID- 16593622
TI  - Crystal and molecular structure of chymotrypsin inhibitor 2 from barley seeds in
      complex with subtilisin Novo.
AB  - The serine proteinase inhibitor from barley seeds, chymotrypsin inhibitor 2(CI
      2), has been crystallized in a molecular complex with subtilisin Novo (EC
      3.4.21.14). The crystal structure of this complex has been determined at 2.1-A
      resolution by the molecular replacement method and partially refined by
      restrained-parameter least-squares methods. The present crystallographic R factor
      (SigmaFo[unk] - [unk]Fc/Sigma[unk]Fo[unk]) is 0.193. CI-2 is a member of the
      potato inhibitor 1 family; it is a serine proteinase inhibitor lacking disulfide
      bonds. Comparison of the subtilisin molecule in this complex with the native
      subtilisin shows that the two molecules are very similar in structure. The
      inhibitor binds in a mode presumably resembling that of a true substrate, but it
      is not cleaved. This is in accord with the reported structures of other serine
      proteinase-inhibitor complexes. CI-2 consists of a four-stranded mixed parallel
      and antiparallel beta-sheet against which an alpha-helix packs to form a
      hydrophobic core. A wide loop crossover connection between parallel strands 2 and
      3 of the beta-sheet contains the reactive-site bond. The conformation of the four
      residues to either side of the reactive-site bond is similar to that of the
      analogous residues in the third domain of the turkey ovomucoid inhibitor (Kazal
      family); the overall polypeptide chain fold of these inhibitors and the location
      of the reactive site in the respective chains are different.

PMID- 16593623
TI  - Changes in Na influx and outflux in Daphnia magna (Straus) as a function of
      elevated Al concentrations in soft water at low pH.
AB  - The effects of aluminum (Al) on sodium (Na) regulation by the freshwater
      crustacean Daphnia magna were determined. (22)Na influx and outflux experiments
      were conducted in soft water adjusted to pH 4.5, 5.0, and 6.5 (reference pH) with
      either ambient (0.02 mg/liter) or high (1.02 mg/liter) concentrations of total
      Al. The results indicate that Al toxicity was pH dependent. Aluminum increased
      the rate of morbidity of D. magna at pH 6.5, had no additional effect to those of
      hydrogen ions (H(+)) at pH 5.0, and reduced the rate of morbidity at pH 4.5. Both
      H(+) and total Al concentrations interfered with Na regulation, although it was
      possible to distinguish between their respective effects by using (22)Na. At pH
      6.5, Al decreased (22)Na influx (by 46%) and increased (22)Na outflux (by 25%),
      which led to a net loss of Na. At pH 5.0, Al reduced (22)Na influx (by 58%) but
      had no additional effect to that of H(+) on (22)Na outflux. At pH 4.5, (22)Na
      influx was significantly inhibited (by 73%) compared with the reference pH 6.5
      treatment even in the absence of Al. Aluminum decreased (22)Na outflux (by 31%)
      at pH 4.5, which reduced the net loss of Na and temporarily prolonged survival of
      the daphnids. These results indicate that Al affects both (22)Na influx and
      outflux in D. magna. The lower rate of Na uptake may involve a denaturation of
      the enzyme responsible for the active uptake of Na. At pH 6.5, the increased
      outflux of (22)Na may be due to either increased membrane permeability or
      increased renal losses (or both). At pH 4.5, the reduced outflux of (22)Na
      resembles the amelioration that occurs in the presence of elevated Ca
      concentrations.

PMID- 16593624
TI  - Isolation and characterization of nodulation genes from Bradyrhizobium sp.
      (Vigna) strain IRc 78.
AB  - An 11.76-kilobase-pair (kb) segment of DNA from Bradyrhizobium sp. (Vigna) strain
      IRc 78 that hybridizes to nodulation genes of Rhizobium meliloti strain 41 was
      isolated. Hybridization of the 11.76-kb DNA fragment to DNA from other
      Bradyrhizobium species revealed a high degree of sequence conservation in this
      region. Transfer of the 11.76-kb segment to nodulation-defective (Nod(-)) mutants
      of R. meliloti restored their ability to induce nodules on Medicago sativa
      (alfalfa). Mutants of strain IRc 78 generated by Tn5 mutagenesis of the 11.76-kb
      segment fell into three classes according to their symbiotic reaction with Vigna
      unguiculata (cowpea). Class I mutants of strain IRc 78 were unable to induce root
      hair curling or to nodulate; class II induced small, ineffective nodules; and
      class III showed delayed and decreased nodulation with reduction in amount of
      nitrogen fixed. Furthermore, in contrast to the wild-type strain, class I mutants
      could not induce nodules on Glycine max (soybean), Cajanus cajan (pigeon pea), or
      Arachis hypogaea (peanut). This finding suggests a common function of the 11.76
      kb region in the infection of host plants by Bradyrhizobium either through root
      hairs or by "crack entry."

PMID- 16593625
TI  - Nonlinear natural engine: Model for thermodynamic processes in mesoscale systems.
AB  - To develop intuition on the possible application of concepts from thermodynamic
      heat engines to mesoscale systems, we have constructed and studied a model
      thermoacoustic heat engine. The model consists of a chain of coupled nonlinear
      acoustic vibrators in which the primary thermodynamic medium is argon gas, the
      secondary thermodynamic medium is constituted by solids bounding the gas, and
      frequencies are ca. 3 x 10(2) Hz. The nonlinear elements are the necks, made
      flexible by means of an oil-loaded DuPont Kapton film, of Helmholtz resonators.
      When the primary medium is driven uniformly by an acoustic driver at a frequency
      somewhat below the low-amplitude resonant frequency and at a high enough driving
      amplitude, stationary localized or solitary states appear irreversibly on the
      chain. These are characterized by a higher vibrational amplitude than that in
      surrounding vibrators, where the amplitude can decrease; by the appearance of
      deep subharmonics of the drive frequency, corresponding to driven low-frequency
      vibrations of the Kapton film-oil systems; and by the pumping of heat toward the
      localized states. Possible implications of these results for mesoscale systems
      consisting of chains of molecular vibrators are then discussed.

PMID- 16593626
TI  - Subunit stoichiometry and juxtaposition of the photosynthetic coupling factor 1:
      Immunoelectron microscopy using monoclonal antibodies.
AB  - Monoclonal antibodies specific to the alpha subunits of the photosynthetic
      coupling factor 1 (CF(1)) were used as marker molecules in an electron
      microscopic analysis of the subunit organization of this enzyme. Immune complexes
      were obtained by incubation of CF(1) with saturating amounts of anti-alpha
      subunit IgG, isolated by gel filtration, and visualized by electron microscopy.
      The maximum number of antibodies bound to a CF(1) molecule was three, the angle
      defined by a neighboring pair of antibodies characteristically being 120 degrees
      . These results are interpreted as direct evidence for the presence of three
      alpha subunits in the CF(1) complex, the relative orientation of them being
      described by 3-fold rotary symmetry. Our observations thus favor an overall
      subunit stoichiometry of alpha(3)beta(3)gammadeltaepsilon.

PMID- 16593627
TI  - Synthesis of pathogenesis-related proteins in tobacco is regulated at the level
      of mRNA accumulation and occurs on membrane-bound polysomes.
AB  - The pathogenesis-related (PR) proteins of tobacco plants are induced in response
      to a variety of pathogenic and chemical agents. Although the function of these
      proteins is unknown, they are associated with resistance to multiplication and/or
      spread of tobacco mosaic virus. We report that functional mRNAs encoding PR
      proteins are present only when synthesis of these proteins has been induced,
      suggesting that their synthesis is controlled in part at the level of mRNA
      accumulation. In addition PR proteins appear to be synthesized and processed in a
      manner analogous to proteins destined for the endoplasmic reticulum since (i) the
      in vitro translation products synthesized in the wheat-germ cell-free system are
      slightly larger than the in vivo products, (ii) translation of PR mRNAs in the
      rabbit reticulocyte lysate system is blocked unless that system is supplemented
      with dog pancreas microsomes, and (iii) mRNAs for PR proteins are associated
      predominantly with membrane-bound polysomes in vivo. This pathway of synthesis
      and posttranslational modification suggests possible sites of action of these
      proteins.

PMID- 16593628
TI  - Kinetic properties of the blue-light response of stomata.
AB  - The stomatal response to blue light was analyzed with gas-exchange techniques in
      Commelina communis L. leaves by using high-fluence-rate short pulses. Pulses of
      blue light were given under a background of high-fluence-rate red light, which
      maintained photosynthesis at near saturation and stomatal conductance at a steady
      state. A single blue light pulse of 1-100 sec induced an increase in stomatal
      conductance, which peaked after 15 min and then returned to the initial steady
      state level within 50-60 min after the pulse. The response could be repeatedly
      induced in the same leaf. Red light pulses on a red background did not induce any
      comparable response. The stomatal response quantified by integrating the
      conductance increases after pulse application approached saturation with
      increasing pulse duration (t((1/2)) approximately 9 sec with 250 mumol.m(-2).sec(
      1) of blue light). After a saturating pulse, sensitivity to a second pulse was
      restored slowly. This recovery response, quantified from the conductance
      increases caused by the two pulses, approached saturation with a t((1/2)) of
      approximately 9 min. These results were used to test a model in which a molecular
      component in the sensory transduction process is considered to exist in two
      interconvertible forms, A and B. If B is the physiologically active form inducing
      stomatal opening, then A is the inactive form. The A to B conversion is a light
      induced reaction and the B to A conversion is a thermal reaction. Rate constants
      for these reactions were estimated from single- and double-pulse experiments (at
      a fluence rate of 250 mumol.m(-2).sec(-1), k(1) = 0.075 sec(-1); thermal rate
      constant k(d) = 0.0014 sec(-1)), allowing the calculation of steady-state
      concentration of B under continuous irradiation. The calculated values accurately
      predicted the steady-state stomatal conductances under continuous blue light.

PMID- 16593629
TI  - Regulation of ribulose bisphosphate carboxylase activity in vivo by a light
      modulated inhibitor of catalysis.
AB  - The activity of ribulose 1,5-bisphosphate carboxylase [RuBPCase; 3-phospho-D
      glycerate carboxylyase (dimerizing), EC 4.1.1.39] in leaf extracts of a number of
      species kept in the dark overnight was found to be very low. This was not the
      result of a change in the activation state or in the amount of enzyme that could
      be extracted from "dark" leaves. Rather, in Phaseolus vulgaris it was due to an
      inhibitor of catalysis that occupied the catalytic site of the enzyme. This
      inhibitor was compartmentalized in the chloroplast and its maximum concentration
      in both dark leaves and in intact chloroplasts made from such leaves was slightly
      in excess of the RuBPCase catalytic site concentration. The inhibitor (a
      phosphate ester) was bound preferentially to the activated form of the enzyme,
      apparently functioning as a positive effector of activation. Treatment of the
      enzyme-inhibitor complex in vitro with alkaline phosphatase could restore
      RuBPCase activity. In vivo, both the initial rate of disappearance and the final
      concentration of inhibitor in intact leaves was found to vary with light
      intensity, and these changes could account for observed light-dependent changes
      in RuBPCase activity, indicating that light modulation of inhibitor concentration
      controlled RuBPCase activity. Recovery of activity in vivo could be inhibited by
      3-(3',4',4-dichlorophenyl)-1,1-dimethylurea.

PMID- 16593630
TI  - Monosynaptic connections made by the sensory neurons of the gill- and siphon
      withdrawal reflex in Aplysia participate in the storage of long-term memory for
      sensitization.
AB  - We have found that in the gill- and siphon- withdrawal reflex of Aplysia, the
      memory for short-term sensitization grades smoothly into long-term memory with
      increased amounts of sensitization training. One cellular locus for the storage
      of the memory underlying short-term sensitization is the set of monosynaptic
      connections between the siphon sensory cells and the gill and siphon motor
      neurons. We have now also found that these same monosynaptic connections
      participate in the storage of the memory underlying long-term Sensitization. We
      examined the amplitudes of the direct synaptic connections produced by siphon
      sensory neurons on the gill motor neuron L7 in nervous systems removed from
      control and from long-term sensitized animals 1 day after the end of long-term
      sensitization training. The connections were significantly larger in long-term
      sensitized animals than in control animals. The finding that long-term memory
      occurs at the same synaptic locus as the short-term memory should facilitate
      study of the cellular and molecular mechanisms involved in the conversion of
      short-term to long-term memory.

PMID- 16593631
TI  - The eigenfunction problem in higher dimensions: Asymptotic theory.
AB  - The spectral problem for linear operators on fully infinite domains is
      considered. A transformation first introduced by Wigner is used to show a number
      of asymptotic results. The method leads to a WKB (Wentzel-Kromers-Brillouin)
      theory for operators in more than one dimension. This includes practical tools
      for the approximate evaluation of spectra and eigenfunctions. Several general
      examples are developed.

PMID- 16593632
TI  - Extension of the statistical theory of resonating valence bonds to
      hyperelectronic metals.
AB  - The statistical treatment of resonating covalent bonds in metals, previously
      applied to hypoelectronic metals, is extended to hyperelectronic metals and to
      metals with two kinds of bonds. The theory leads to half-integral values of the
      valence for hyperelectronic metallic elements.

PMID- 16593633
TI  - Comparison of theoretical and experimental values of the number of metallic
      orbitals per atom in hypoelectronic and hyperelectronic metals.
AB  - The statistical resonating-valence-bond theory of metals is applied in the purely
      theoretical calculation of the composition of the Ni-Cu alloy at the foot of the
      curve of saturation ferromagnetic moment, which marks the boundary between
      hypoelectronic and hyperelectronic metals and determines the value of the number
      of metallic orbitals per atom. The results, Ni(44)Cu(56) and 0.722 metallic
      orbitals, agree with the observed values. This agreement provides strong support
      of the theory.

PMID- 16593634
TI  - Driving force and nucleophilicity in S(N)2 displacements.
AB  - The free energies of activation for reaction of six anionic nucleophiles with
      methyl iodide in dimethylformamide correlate linearly with the overall heats of
      reaction in the gas phase. The result indicates that nucleophilicity in this
      S(N)2 displacement reaction is dominated by electron affinity and bond-strength
      effects.

PMID- 16593635
TI  - Calculus of twisted vertex operators.
AB  - Starting from an arbitrary isometry of an arbitrary even lattice, twisted and
      shifted vertex operators are introduced. Under commutators, these operators
      provide realizations of twisted affine Lie algebras. This construction,
      generalizing a number of known ones, is based on a self-contained "calculus."

PMID- 16593636
TI  - Analysis of optical spectra from single crystals of Rhodopseudomonas viridis
      reaction centers.
AB  - Absorption spectra and light-induced absorbance changes of crystals from
      Rhodopseudomonas viridis reaction centers are recorded. A theoretical analysis of
      the absorption and circular dichroism spectra is presented, yielding a consistent
      picture of spectroscopic and structural information.

PMID- 16593637
TI  - Preimaginal learning as a basis of colony-brood recognition in the ant
      Cataglyphis cursor.
AB  - In most circumstances, social insects recognize their nestmates. They can
      discriminate against alien adults and also against alien larvae. Results
      presented here indicate that the mechanism of colony-brood recognition is
      acquired in large part during larval life and persists through the metamorphosis
      into the adult stage. During the first days after emergence of the adult, a
      weaker form of learning can also occur. These phenomena are discussed in relation
      to kinship theory. It appears that kin recognition is determined not so much by
      genetic relatedness as by spatial proximity of the individuals during the early
      stages of life.

PMID- 16593638
TI  - Size and behavior in ants: Constraints on complexity.
AB  - In this paper I investigate the behavioral complexity of ants in relation to
      brain size. The volume of the corpora pedunculata, involved in the selection of
      motor programs, and the antennal lobes, involved in processing olfactory
      information, are directly related to the volume of the brain of an ant. The
      volume of the optic lobe, involved in visual processing, is not related to total
      brain volume. Brain volume is allometrically related to head width in ants.
      Behavioral complexity, as assayed by the size of the behavioral repertoire within
      the nest, is directly related to the cube of head width. Behavioral complexity is
      thus related to the 3/2 power of brain volume. The size of the behavioral
      repertoire does not appear to correlate with any ecological characteristics of
      the species but may be a passive consequence of body size. Determination of body
      size by numerous ecological factors may place constraints on the complexity of
      behavior that an ant can achieve.

PMID- 16593639
TI  - Detection of simple polygenic segregations in a natural population.
AB  - Penetrance frequencies were used to quantify segregating polygenic effects in a
      natural population of Drosophila melanogaster. When males from a series of 100
      isofemale strains were crossed to females from a veinlet (ve) line that had been
      selected for shortened veins, gaps commonly appeared in the fifth longitudinal
      (L5) vein in the ve/+ heterozygotes. We were able to assign each strain to one of
      six significantly different clusters, based upon the pattern of polygenic
      modifiers of ve dominance segregating in each strain. We conclude that the
      extensive range of phenotypic variation in vein-forming ability is actually based
      upon a relatively simple underlying polygenic structure that is consistent with
      segregation of only a small number of alleles or allele combinations in the wild
      population.

PMID- 16593640
TI  - Oscillatory singular integrals and harmonic analysis on nilpotent groups.
AB  - Several related classes of operators on nilpotent Lie groups are considered.
      These operators involve the following features: (i) oscillatory factors that are
      exponentials of imaginary polynomials, (ii) convolutions with singular kernels
      supported on lower-dimensional submanifolds, (iii) validity in the general
      context not requiring the existence of dilations that are automorphisms.

PMID- 16593641
TI  - Origin and evolution of the transcribed repeated sequences of the Y chromosome
      lampbrush loops of Drosophila hydei.
AB  - The molecular evolution and patterns of conservation of clones from four Y
      chromosome lampbrush loops of Drosophila hydei were investigated. Each loop
      contains a discrete family of transcribed repeats that are only slightly
      conserved even in the hydei subgroup species. Sequencing of clones from the four
      D. hydei loops indicates that all transcribed repeats evolved from A+T-rich
      elements of the genome. Evidence is presented that suggests a Y-specific family
      evolved as a result of the transposition of repeated sequences from an autosomal
      site to the Y chromosome with the concomitant acquisition of transcriptional
      activity and loss of non-Y sequences. The results support a structural role for
      the loops in shaping a spermatocyte-specific nuclear organization. Transcribed
      heterochomatic sequences could play a similar role in nuclear organization in
      many cell types.

PMID- 16593642
TI  - NMR imaging shows water distribution and transport in plant root systems in situ.
AB  - Images of Vicia faba L. root systems at 0.6-mm resolution, undisturbed and within
      the soil medium in which they were grown, have been obtained by using a 1.5-Tesla
      proton ((1)H) NMR medical imaging research system. Images of root systems in
      seven soil media (Cahaba soil, vermiculite, sand, perlite, fritted clay, potting
      soil, and peatlite) exhibited variable but useful quality owing to a diversity of
      magnetic properties of the soils. Root structure and pathology in the form of
      partial decay of hypogeal cotyledons were easily discernible. Water transport in
      roots with light-stressed foliage was demonstrated by using water doped with a
      paramagnetic NMR contrast agent, and the process of plant-wilt and recovery was
      monitored in situ. Images of germinated seeds within soil media indicated that
      dynamic observations of germination and growth are possible. The results suggest
      that NMR imaging can be an effective noninvasive tool for studying plants in
      situ.

PMID- 16593643
TI  - Lateral diffusion of phospholipids in the plasma membrane of soybean protoplasts:
      Evidence for membrane lipid domains.
AB  - Fluorescent lipid and phospholipid probes were incorporated at 4 degrees C into
      soybean protoplasts prepared from cultured soybean (SB-1) cells. Fluorescence
      microscopy showed that the plasma membrane as well as the nucleus were labeled.
      Fluorescence redistribution after photobleaching (FRAP) analysis was performed on
      these cells at 18 degrees C to monitor the lateral mobility of the incorporated
      probes. After labeling at low concentrations (40 mug/ml) of phosphatidyl-N-(4
      nitrobenzo-2-oxa-1,3-diazolyl)ethanolamine (NBD-PtdEtn), a single mobile
      component was observed with a diffusion coefficient (D) of approximately 3 x 10(
      9) cm(2)/sec. After labeling at higher probe concentrations (>/=100 mug/ml), two
      diffusing species were observed, with diffusion coefficients of approximately 3 x
      10(-9) cm(2)/sec ("fast") and approximately 5 x 10(-10) cm(2)/sec ("slow").
      Similar results were observed with fluorescent derivatives of phosphatidylcholine
      and fatty acids. In contrast to these results, parallel analysis of 3T3
      fibroblasts, using the same probes and conditions, yielded only a single
      diffusion component. These results suggest that the soybean plasma membrane may
      contain two distinct lipid domains in terms of lipid mobility. Consistent with
      this idea, experiments with soybean protoplasts yielded a single diffusion
      component under the following conditions: (i) labeling with NBD-PtdEtn (100
      mug/ml), FRAP analysis at 37 degrees C (D = 1.1 x 10(-8) cm(2)/sec); (ii)
      labeling with NBD-PtdEtn (100 mug/ml), FRAP analysis at 18 degrees C in the
      presence of 2 mM EGTA (D = 4.2 x 10(-9) cm(2)/sec); (iii) labeling with 5-(N
      dodecanoyl)aminofluorescein (a short-chain lipid probe), FRAP analysis at 18
      degrees C or 37 degrees C (D = 2.5 x 10(-8) cm(2)/sec). These results suggest
      that the plasma membrane of soybean cells may contain stable immiscible domains
      of fluid and gel-like lipids.

PMID- 16593644
TI  - Deconvolution of non-Gaussian linear processes with vanishing spectral values.
AB  - We consider the problem of estimating the filter generating a non-Gaussian linear
      process and the deconvolution of that process when the spectral density of the
      process has zeros. Without using a minimum phase assumption we show that often if
      there are only finitely many zeros there are procedures to effect such an
      estimation and deconvolution.

PMID- 16593645
TI  - Yields of Soviet underground nuclear explosions at Novaya Zemlya, 1964-1976, from
      seismic body and surface waves.
AB  - Surface and body wave magnitudes are determined for 15 U.S.S.R. underground
      nuclear weapons tests conducted at Novaya Zemlya between 1964 and 1976 and are
      used to estimate yields. These events include the largest underground explosions
      detonated by the Soviet Union. A histogram of body wave magnitude (m(b)) values
      indicates a clustering of explosions at a few specific yields. The most
      pronounced cluster consists of six explosions of yield near 500 kilotons. Several
      of these seem to be tests of warheads for major strategic systems that became
      operational in the late 1970s. The largest Soviet underground explosion is
      estimated to have a yield of 3500 +/- 600 kilotons, somewhat smaller than the
      yield of the largest U.S. underground test. A preliminary estimation of the
      significance of tectonic release is made by measuring the amplitude of Love
      waves. The bias in m(b) for Novaya Zemlya relative to the Nevada test site is
      about 0.35, nearly identical to that of the eastern Kazakhstan test site relative
      to Nevada.

PMID- 16593646
TI  - On the automorphism group of the conformal superalgebra.
AB  - There is no automorphism of the conformal superalgebra that induces PT (parity
      and time reversal) on space time. Those conformal transformations that induce PT
      must change the sign of the odd brackets. In particular, in any implementation of
      conformal supersymmetry, CP can preserve but CPT must (at best) reverse the sign
      of the odd brackets (C, charge conjugation).

PMID- 16593647
TI  - Specific heat shock proteins are transported into chloroplasts.
AB  - We demonstrate that in three plant species-soybean, pea, and corn-certain nuclear
      encoded heat shock proteins are transported into chloroplasts. In vitro
      translation products of poly(A)-RNA from control or heat-shocked plants were
      incubated with isolated intact pea chloroplasts and differences in the profile of
      imported proteins were analyzed. In all three species, abundant polypeptides
      between 21 and 27 kDa are present in the heat shock sample and absent in the
      controls. These polypeptides are protected from trypsin and chymotrypsin
      digestion after their import into chloroplasts and are recovered primarily with
      the soluble chloroplast protein fraction. Chloroplasts isolated from pea or corn
      leaves labeled in vivo at heat shock temperatures, but not at normal growth
      temperatures, contain the same polypeptides observed in vitro. Synthesis of the
      heat shock polypeptides can be inhibited in vivo by cycloheximide but not by
      chloramphenicol, further indicating they are products of cytoplasmic protein
      synthesis. The in vitro transport experiments demonstrate that synthesis of the
      chloroplast-localized heat shock proteins results from heat-induced accumulation
      of the corresponding poly(A)-RNAs. The same mRNAs are also produced in response
      to heat shock by a nonphotosynthetic tissue, the etiolated soybean hypocotyl.

PMID- 16593648
TI  - A plant cell factor induces Agrobacterium tumefaciens vir gene expression.
AB  - The virulence genes of Agrobacterium are required for this organism to
      genetically transform plant cells. We show that vir gene expression is
      specifically induced by a small (<1000 Da) diffusible plant cell metabolite
      present in limiting quantities in the exudates of a variety of plant cell
      cultures. Active plant cell metabolism is required for the synthesis of the vir
      inducing factor, and the presence of bacteria does not stimulate this production.
      vir-inducing factor is (i) heat and cold stable; (ii) pH stable, although vir
      induction with the factor is sensitive above pH 6.0; and (iii) partially
      hydrophobic. Induction of vir gene expression was assayed by monitoring beta
      galactosidase activity in Agrobacterium strains that carry gene fusions between
      each of the vir loci and the lacZ gene of Escherichia coli. vir-inducing factor
      (partially purified on a C-18 column) induces both the expression in
      Agrobacterium of six distinct loci and the production of T-DNA circular
      molecules, which are thought to be involved in the transformation process. vir
      inducing factor potentially represents the signal that Agrobacterium recognizes
      in nature as a plant cell susceptible to transformation.

PMID- 16593649
TI  - The eigenfunction problem in higher dimensions: Exact results.
AB  - A hermitian integral kernel in N-space may be mapped to a corresponding
      Hamiltonian in 2N-space by the Wigner transformation. Linear simplectic
      transformation on the phase space of the Hamiltonian yields a new kernel whose
      spectrum is unchanged and whose eigenfunctions follow from an explicit unitary
      transformation. If an integral kernel has a Wigner transform whose surfaces of
      constant value are concentric ellipsoids, then the Wigner transform yields exact
      results to the eigenfunction problem. Such behavior is asymptotically generic
      near extrema of the Wigner transform, from which follow simple and robust
      asymptotic results for the ends of the eigenvalue spectrum and for the
      corresponding eigenfunctions.

PMID- 16593650
TI  - Reconstruction of the dynamics of the climatic system from time-series data.
AB  - The oxygen isotope record of the last million years, as provided by a deep sea
      core sediment, is analyzed by a method recently developed in the theory of
      dynamical systems. The analysis suggests that climatic variability is the
      manifestation of a chaotic dynamics described by an attractor of fractal
      dimensionality. A quantitative measure of the limited predictability of the
      climatic system is provided by the evaluation of the time-correlation function
      and the largest positive Lyapounov exponent of the system.

PMID- 16593651
TI  - Maximum likelihood estimation for stationary point processes.
AB  - In this paper we derive the log likelihood function for point processes in terms
      of their stochastic intensities by using the martingale approach. For practical
      purposes we work with an approximate log likelihood function that is shown to
      possess the usual asymptotic properties of a log likelihood function. The
      resulting estimates are strongly consistent and asymptotically normal (under some
      regularity conditions). As a by-product, a strong law of large numbers and a
      central limit theorem for martingales in continuous times are derived.

PMID- 16593652
TI  - Dissipative structures in a two-cell system: Numerical and experimental
      approaches.
AB  - It has been shown that the coupling between the photoreduction of the oxidized
      form of dichloroindophenol (an artificial electron acceptor) by thylakoids and
      the incident light intensity can lead to the appearance of multiple steady states
      when the system is operated under open conditions. In the present work, a
      numerical study and experimental evidence are presented on the occurrence of
      dissipative structures in an arrangement of two continuously stirred tank
      reactors with mutual mass exchange of dichloroindophenol through an inert
      membrane. The stable spatial structures are generated by the creation of
      transient internal and external asymmetries. A nontrivial hysteresis effect
      between symmetric and asymmetric stable steady states has been observed.

PMID- 16593653
TI  - Choline kinase II is present only in nodules that synthesize stable peribacteroid
      membranes.
AB  - Host-cell cytoplasm from soybean plants infected with the peribacteroid membrane
      (PBM)-building Rhizobium japonicum strain 61-A-101 (effective, N(2)-fixing) had
      much higher choline kinase activity than cytoplasm from either uninfected tissue
      or tissue infected with the non-PBM-building (ineffective, non-N(2)-fixing)
      strain 61-A-24. Ion-exchange chromatography showed that both types of nodule and
      root tissue possessed constitutive choline kinase I activity that had a K(m) for
      choline of approximately 150 muM. The nodules of the effective symbiosis had
      another activity, choline kinase II (K(m) = 81 muM). Nondenaturing and NaDodSO(4)
      electrophoresis revealed no multimeric subunit structure of the two enzyme forms
      but did show the molecular sizes for choline kinase I, 58-59 kDa, and choline
      kinase II, 60 kDa. Choline kinase I and II and pI values of 8.1 and 8.5,
      respectively, and two-dimensional gel electrophoresis of whole cytoplasm from
      control and infected tissue showed a spot corresponding to choline kinase II only
      in the case of the effective symbiosis, whereas both tissue types had spots
      corresponding to choline kinase I. Choline kinase II is presumed to be encoded by
      the plant as neither free-living nor symbiotic (bacteroid) forms of the
      prokaryote showed any choline kinase activity.

PMID- 16593654
TI  - High-efficiency genetic transformation of maize by a mixture of pollen and
      exogenous DNA.
AB  - High-efficiency genetic transformation was induced in a genetic stock of maize,
      Zea mays Linnaeus, by self-pollination of the recipient plants along with DNA of
      the donor. The highest frequency of transformed endosperm per ear was 9.29%. DNA
      was applied onto silks in a pollen/DNA pasty mixture. The exogenous DNA
      transferred into endosperm expressed itself in endosperm formation. It is not
      known, however, whether the exogenous DNA segment in endosperm had been
      incorporated or whether it was present in the nucleus additionally, fragmentally,
      or in some other state. It was revealed that all of four possible cases had
      occurred as follows: exogenous DNA was transferred into (i) both embryo and
      endosperm of the same kernel, (ii) embryo only, (iii) endosperm only, and (iv)
      neither embryo nor endosperm. It was also revealed that exogenous DNA that had
      entered into the embryo had been maintained through embryo formation,
      germination, vegetative growth and differentiation, and reproductive growth, and
      finally was manifested in embryo and/or endosperm of the following generation and
      acted in endosperm formation. The frequency of transformed endosperm in this
      generation, however, was rather low. It may be that exogenous DNA taken into the
      embryo was unstable.

PMID- 16593655
TI  - Extinction of Harrington's mountain goat.
AB  - Keratinous horn sheaths of the extinct Harrington's mountain goat, Oreamnos
      harringtoni, were recovered at or near the surface of dry caves of the Grand
      Canyon, Arizona. Twenty-three separate specimens from two caves were dated
      nondestructively by the tandem accelerator mass spectrometer (TAMS). Both the
      TAMS and the conventional dates indicate that Harrington's mountain goat occupied
      the Grand Canyon for at least 19,000 years prior to becoming extinct by 11,160 +/
      125 radiocarbon years before present. The youngest average radiocarbon dates on
      Shasta ground sloths, Nothrotheriops shastensis, from the region are not
      significantly younger than those on extinct mountain goats. Rather than
      sequential extinction with Harrington's mountain goat disappearing from the Grand
      Canyon before the ground sloths, as one might predict in view of evidence of
      climatic warming at the time, the losses were concurrent. Both extinctions
      coincide with the regional arrival of Clovis hunters.

PMID- 16593656
TI  - Calderon-Zygmund theory for product domains: H spaces.
AB  - This article deals with the boundedness properties of singular integrals that
      generalize the double Hilbert transform on product domains. The action of these
      operators on Hardy spaces and on L(log L) is discussed.

PMID- 16593657
TI  - Symbolic method in invariant theory.
AB  - A symbolic method based on an extension of the straightening algorithm is
      developed for the representation of joint invariants of symmetric and skew
      symmetric tensors. For skew-symmetric tensors, the method holds over infinite
      fields of arbitrary characteristic.

PMID- 16593658
TI  - On the relationship among three theories of relaxation in disordered systems.
AB  - Empirical evidence has accumulated showing the wide occurrence of a stretched
      exponential relaxation decay law for many diverse condensed-matter systems.
      Several theories based on different physical mechanisms have been successful in
      deriving the stretched-exponential decay law in a natural way. Three of these
      theories, the direct-transfer model, the hierarchically constrained dynamics
      model, and the defect-diffusion model are shown here to have an underlying common
      mathematical structure.

PMID- 16593659
TI  - Femtosecond spectroscopy of electron transfer in the reaction center of the
      photosynthetic bacterium Rhodopseudomonas sphaeroides R-26: Direct electron
      transfer from the dimeric bacteriochlorophyll primary donor to the
      bacteriopheophytin acceptor with a time constant of 2.8 +/- 0.2 psec.
AB  - The primary light-induced charge separation in reaction centers from
      Rhodopseudomonas sphaeroides R-26 has been investigated after excitation with
      laser pulses of 150 fsec duration within the longwave absorption band of the
      primary donor at 850 nm. An excited state of the primary donor, characterized by
      a broad absorption spectrum extending over the whole spectral range investigated
      (545-1240 nm), appeared within 100 fsec and gave rise to stimulated emission in
      the 870- to 1000-nm region with a 2.8-psec lifetime. The photooxidation of the
      primary donor, as measured at 1240 nm, and the photoreduction of the
      bacteriopheophytin acceptor, monitored at 545 nm and 675 nm, have been found to
      proceed simultaneously with a time constant of 2.8 +/- 0.2 psec. Kinetics of
      absorbance changes at other probe wavelengths gave no indication that an
      accessory bacteriochlorophyll is involved as a transient electron acceptor.

PMID- 16593660
TI  - Zeatin biosynthesis from N-(Delta-isopentenyl)adenine in Actinidia and other
      woody plants.
AB  - Tissue cultures of Actinidia kolomikta can be maintained as callus through
      repeated passages on a nutrient medium devoid of cytokinin but containing
      inorganic nutrients, sucrose, and other basal organics plus auxin. Under these
      conditions, actively growing callus contained 2 and 0.5 nmol of the cytokinins
      zeatin [io(6)Ade; 6-(4-hydroxy-3-methylbut-2-enylamino)purine] and N(6)-(Delta(2)
      isopentenyl)adenine (i(6)Ade), respectively, per gram (fresh weight). When
      tissues were transferred from cytokininless medium to 30 muM i(6)Ade, endogenous
      io(6)Ade increased linearly to 160 nmol/g (fresh weight) during 8 hr, and i(6)Ade
      increased to 5 nmol/g (fresh weight) in 2 hr and then declined. The apparent K(m)
      for i(6)Ade in A. kolomikta and Actinidia chinensis x Actinidia arguta callus and
      in tissue slices of A. arguta stems was 12 muM. In addition, the reaction(s)
      converting i(6)Ade to io(6)Ade was O(2)-requiring and specific for i(6)Ade versus
      N(6)-(Delta(2)-isopentenyl)adenosine (i(6)A). When A. kolomikta callus was fed 30
      muM i(6)A, io(6)Ade increased and reached a concentration corresponding to 6
      nmol/g (fresh weight) in 8 hr. Ribosylzeatin (io(6)A) did not increase. Under
      N(2) during i(6)A feeds, i(6)A accumulated rather than being metabolized to
      i(6)Ade, suggesting that i(6)A normally may be metabolized via i(6)AMP and
      i(6)Ade to io(6)Ade. A survey of 30 species of woody plants in 20 families of
      dicotyledonous angiosperms indicated that the ability to accumulate io(6)Ade
      (>/=10 nmol/g) in 24-hr feeds with 30 muM i(6)Ade was restricted to certain
      systematic groups-e.g., order Ericales, families Oleaceae and Rubiaceae. This
      suggests that plants may differ in their pathways for io(6)Ade biosynthesis and
      that cytokinin biochemistry has potential as a taxonomic character above the
      species and genus levels.

PMID- 16593661
TI  - The nil Hecke ring and cohomology of G/P for a Kac-Moody group G.
AB  - Let G be the group with Borel subgroup B, associated to a Kac-Moody Lie algebra
      [unk] (with Weyl group W and Cartan subalgebra [unk]). Then H(*)(G/B) has, among
      others, four distinguished structures (i) an algebra structure, (ii) a
      distinguished basis, given by the Schubert cells, (iii) a module for W, and (iv)
      a module for Hecke-type operators A(w), for w [unk] W. We construct a ring R,
      which we refer to as the nil Hecke ring, which is very simply and explicitly
      defined as a functor of W together with the W-module [unk] alone and such that
      all these four structures on H(*)(G/B) arise naturally from the ring R.

PMID- 16593662
TI  - An optimal property of the repeated significance test.
AB  - It is shown that the repeated significance test is a Bayes test for testing
      sequentially the sign of the drift of a Brownian motion. Its relation to Wald's
      sequential probability ratio test is studied.

PMID- 16593663
TI  - Benzyl acetates as attractants for the male oriental fruit fly, Dacus dorsalis,
      and the male melon fly, Dacus cucurbitae.
AB  - Fifty compounds related to benzyl acetate were evaluated quantitatively as
      attractants to the male oriental fruit fly (Dacus dorsalis) and the male melon
      fly (Dacus cucurbitae). Thienylmethyl acetate was nearly as attractive as benzyl
      acetate to both species, but cyclohexylmethyl acetate was completely
      unattractive, emphasizing the role of the planar aromatic ring in receptor
      interaction. Although benzyl acetate was equally attractive to both species, para
      substituents invariably reduced attraction to the oriental fruit fly. A number of
      derivatives, including p-hydroxy-, p-methoxy-, p-acetoxy-, and p-cyanobenzyl
      acetates were highly attractive to the melon fly. Selective fluorination
      indicated that the polarizability of the carbonyl carbon is important in receptor
      interaction with the melon fly but is not specifically involved in the oriental
      fruit fly. Attraction to the melon fly was lost with ortho, meta, or dimethoxy
      substitution of benzyl acetate, but the 3,4- and 2,5-dimethoxybenzyl acetates
      were attractive to the oriental fruit fly. These results are interpreted in terms
      of specific olfactory receptor interactions for the two species of fruit flies.

PMID- 16593664
TI  - Primary electron transfer reactions in modified reaction centers from
      Rhodopseudomonas sphaeroides.
AB  - Absorption spectra were measured by means of an optical multichannel analyzer in
      Rhodopseudomonas sphaeroides R-26 reaction centers (RCs) modified by treatment
      with NaBH(4) at various times (>/=1 ps) after the onset of a short excitation
      flash at 880 nm. Most of these RCs (75-95%) have only one "monomeric"
      bacteriochlorophyll-800 (B(1)) molecule and are as active as the original RCs.
      The duration of the excitation and measuring pulses was approximately 33 ps. If
      the center of the excitation pulse preceded the center of the measuring pulse by
      36-40 ps, the formation of a state P(E) (early state), which is converted to the
      state P(F) (P(+) bacteriopheophytin(-)) in 4 +/- 1 ps (1/e time), was observed.
      Also the kinetics and the spectrum of the stimulated emission (reflecting the
      kinetics and the emission spectrum of the excited state P(*)) were determined.
      The difference spectrum of the state P(E) approximately equals the sum of the
      spectra of the states P(*) ( approximately 65%) and (1)[P(+)B(1) (-)] (
      approximately 35%). This indicates that B(1) (-) is an intermediate in the
      electron transfer from P(*) to bacteriopheophytin, H(1), transferring this
      electron with a rate constant of (4 x 0.35 ps)(-1) = 7 x 10(11) s(-1).

PMID- 16593665
TI  - Excitation trapping and primary charge stabilization in Rhodopseudomonas viridis
      cells, measured electrically with picosecond resolution.
AB  - The transmembrane primary charge separation in the photosynthetic bacterium
      Rhodopseudomonas viridis was monitored by electric measurements of the light
      gradient type [Trissl, H. W. & Kunze, U. (1985) Biochim. Biophys. Acta 806, 136
      144]. Excitation of whole cells with 30-ps laser pulses at either 532 nm or 1064
      nm gave rise to a biphasic increase of the photovoltage. The fast phase,
      contributing about 50% of the total, rose with an exponential time constant </=40
      ps and was independent of the redox state of the quinone electron acceptor. It is
      assigned to the migration of the excitation energy in the antenna and its
      subsequent trapping by the reaction center, monitored by the ultrafast charge
      separation between the primary electron donor and the bacteriopheophytin
      intermediary acceptor. The slower phase (125 +/- 50 ps) only occurred when the
      quinone was oxidized and disappeared when it was reduced (either chemically or
      photochemically). It is assigned to the forward electron transfer from the
      bacteriopheophytin to the quinone. The relative amplitudes of these two
      electrogenic steps demonstrate that the bacteriopheophytin intermediary acceptor
      is located halfway between the primary donor and the quinone.

PMID- 16593666
TI  - Mechanism by which contact with plant cuticle triggers cutinase gene expression
      in the spores of Fusarium solani f. sp. pisi.
AB  - Spores of the phytopathogenic fungus Fusarium solani f. sp. pisi were shown to
      produce the extracellular enzyme, cutinase, only when cutin or cutin hydrolysate
      was added to the spore suspension. Dihydroxy-C(16) acid and trihydroxy-C(18)
      acid, which are unique cutin monomers, showed the greatest cutinase-inducing
      activity. Experiments with several compounds structurally related to these fatty
      acids suggested that both a omega-hydroxyl and a midchain hydroxyl are required
      for cutinase-inducing activity. Cutinase appeared in the medium 30-45 min after
      the addition of the inducers to the spore suspension, and the activity level
      increased for 6 hr. Addition of cycloheximide (5 mug/ml) completely inhibited
      cutinase production, suggesting that protein synthesis was involved in the
      increase of cutinase activity. Immunoblot analysis with rabbit antibodies
      prepared against cutinase showed that cutinase protein increased in parallel with
      the increase in enzyme activity. Measurement of cutinase-specific RNA levels by
      dot-blot hybridization with (32)P-labeled cutinase cDNA showed that the cutinase
      gene transcripts could be detected within 15 min after addition of the inducers.
      Addition of exogenous cutinase greatly enhanced the level of cutinase gene
      transcripts induced by cutin. These results strongly suggest that the fungal
      spore senses that it is in contact with the plant by the production of small
      amounts of cutin monomers catalyzed by the low level of cutinase carried by the
      spore and that these monomers induce the synthesis of cutinase needed for
      penetration of the fungus into the plant.

PMID- 16593667
TI  - Visualization of the Ca-transport system of the mitotic apparatus of sea urchin
      eggs with a monoclonal antibody.
AB  - Monoclonal antibodies have been obtained to components of Ca(2+)-sequestering
      vesicles from the endoplasmic reticulum of HeLa cells by isolating hybridomas
      that were generated by the in vitro immunization of lymphocytes followed by
      fusion with plasmocytoma cells. One of these monoclonal antibodies specifically
      labels punctate structures which appear in the mitotic apparatus of sea urchin
      eggs at the beginning of prophase and disappear upon the completion of
      cytokinesis. The antibody inhibits the Ca(2+) uptake of the membrane system in
      vitro. It reacts with one 46-kDa protein out of the complex protein mixture from
      the membrane fraction. We take all this as evidence that in fact a specific
      Ca(2+)-transport system is part of the mitotic apparatus, that such a system is
      very conserved, and that it is most probably derived from the endoplasmic
      reticulum.

PMID- 16593668
TI  - Conservation of extended promoter regions of nodulation genes in Rhizobium.
AB  - A 47-base-pair (bp) conserved sequence in the 5'-flanking regions of three
      transcriptional units coding for nodulation functions (nodABC, nodEFG, and nodH)
      has been identified in Rhizobium meliloti strain 41. The conserved region
      contains subsequences of 7 bp, 5 bp, and 25 bp. The conserved 25-bp sequence was
      synthesized and used as a hybridization probe; three additional copies of the
      sequence were identified in R. meliloti 41; all three were localized in the 135
      kb nod/nif region of the symbiotic megaplasmid. Nucleotide sequence analysis of
      the six regions revealed that all contained the 47-bp conserved sequence but,
      with one exception, adjacent DNA regions did not have long conserved DNA
      stretches. The position of the 47-bp region was about 200-240 bp upstream of the
      translational start codons of the three nod genes. This conserved sequence is
      present in several other Rhizobium species and located adjacent to nod genes. We
      have demonstrated the involvement of this sequence in the expression of
      nodulation functions, which suggests that these extended promoter regions may
      have a role in the coordinated regulation of nodulation genes.

PMID- 16593669
TI  - cDNA cloning of the complete genome of tobacco mosaic virus and production of
      infectious transcripts.
AB  - The entire genome of tobacco mosaic virus (TMV) was copied into a series of
      subgenomic cDNA clones. cDNA sequences of the 5' and 3' ends of TMV were cloned
      separately. A synthetic oligonucleotide primer was used to generate a Pst I site
      at the 5' terminus, whereas a different primer was used to generate an Nde I site
      at the 3' terminus. This strategy permitted removal of non-TMV sequences from
      cloned cDNA inserts by treatment with exonuclease VII following restriction
      endonuclease cleavage. Pst I linkers were added to TMV 3' terminal cDNAs.
      Subgenomic cDNA fragments were ligated together into several independent full
      genomic constructions from which TMV cDNA sequences could be cleanly excised as a
      single fragment by Pst I digestion. Full-genomic TMV cDNA was ligated immediately
      downstream from the lambda phage promoter from pPM1 and transcribed in vitro with
      Escherichia coli RNA polymerase. RNA transcripts from three of four full-genomic
      cDNA constructions were infectious, even though they contained 6 non-TMV
      nucleotides at the 3' end. Transcripts from a construction with 6 extra
      nucleotides at the 5' end also were infectious. Progeny virus from plants
      infected with cDNA transcripts appeared identical to the parental virus.
      Restriction maps of independent cDNA clones of the same regions of the genome
      were identical to each other and as predicted from the reported nucleotide
      sequence of TMV. Also, sequences of the 200 nucleotides proximal to the 5'
      termini of four independent cDNA clones were identical to each other and to
      published sequences, suggesting that independent isolates of TMV may have
      remarkably similar sequences.

PMID- 16593671
TI  - Cosmogenic He in terrestrial rocks: The summit lavas of Maui.
AB  - We have identified terrestrial cosmic rayproduced (3)He in three lava flows on
      the crest of Haleakala Volcano on Maui, 3 km above sea level, and approximately
      0.5 million years old. Although these lavas, like all oceanic basalts, contain
      primordial (3)He from the mantle, the "cosmogenic" component ((3)He(C)) can be
      identified unambiguously because it is extractable only by high-temperature
      vacuum fusion. In contrast, a large fraction of the mantle helium resides in
      fluid inclusions and can be extracted by vacuum crushing, leaving a residual
      component with (3)He/(4)He ratios as high as 75x those in the atmosphere, which
      can be liberated by melting the crushed grains. Cosmogenic (3)He is present in
      both olivines and clinopyroxenes at 0.8-1.2 x 10(-12) ml(STP)/g and constitutes
      75% +/- 5% of the total (3)He present. The observed (3)He(C) levels require a
      cosmic ray exposure age of only some 64,000 years, much less than the actual age
      of the lavas, if there is no erosion. Using a model that includes effects of
      uplift or submergence as well as erosion, we calculate an apparent "erosion rate"
      of the order of 8.5 m/10(6) years for the western rim of the summit crater, as an
      example of the application of measurements of cosmogenic rare gases to
      terrestrial geological problems.

PMID- 16593670
TI  - Bacterial delta-aminolevulinic acid synthase activity is not essential for
      leghemoglobin formation in the soybean/Bradyrhizobium japonicum symbiosis.
AB  - Previous studies of legume nodules have indicated that formation of the heme
      moiety of leghemoglobin is a function of the bacterial symbiont. We now show that
      a hemA mutant of Bradyrhizobium japonicum that cannot carry out the first step in
      heme biosynthesis forms fully effective nodules on soybeans. The bacterial mutant
      strain was constructed by first isolating the wild-type hemA gene encoding delta
      aminolevulinic acid synthase (EC 2.3.1.37) from a cosmid library, using a
      fragment of the Rhizobium meliloti hemA gene as a hybridization probe. A deletion
      of the hemA gene region, generated in vitro, then was used to construct the
      analogous chromosomal mutation by gene-directed mutagenesis. The mutant strain
      had no delta-aminolevulinic acid synthase activity and was unable to grow in
      minimal medium unless delta-aminolevulinic acid was added. Despite its
      auxotrophy, the mutant strain incited nodules that appeared normal, contained
      heme, and were capable of high levels of acetylene reduction. These results rule
      out bacterial delta-aminolevulinic acid synthase activity as the exclusive source
      of delta-aminolevulinic acid for heme formation in soybean nodules.

PMID- 16593672
TI  - Solution of an inverse problem for fractals and other sets.
AB  - The problem of providing succinct approximate descriptions of given bounded
      subsets of R(n) can be solved by application of the contraction mapping
      principle.

PMID- 16593673
TI  - Solution of Dirac's equation in Reissner-Nordstrom geometry.
AB  - The nature of the singularity at the origin of the solution of Dirac's equation
      in Reissner-Nordstrom geometry is different from that in flat space. Here, both
      independent solutions are regular at the origin, and both give a convergent
      normalization integral. The choice between the two solutions is made by requiring
      that the variational integral, from which the differential equation can be
      derived, be convergent. The gravitational shift of the ground state of hydrogen
      in Reissner-Nordstrom geometry is estimated to be only of order 10(-36) MH.

PMID- 16593674
TI  - Long polypeptide 3(10)-helices at atomic resolution.
AB  - The crystal-state preferred conformation of the terminally blocked
      homooctapeptide from the C(alpha,alpha)-dimethylated alpha-aminoisobutyric acid
      (Aib) residue, pBrBz-(Aib)(8)-OBu(t), in which pBrBz is para-bromobenzoyl and
      OBu(t) is tert-butoxy, determined by x-ray diffraction analysis using direct
      methods, was found to be a 3(10)-helix stabilized by six consecutive
      intramolecular N-H....O=C hydrogen bonds of the C(10)-III (or III') type. This is
      the first observation at atomic resolution of a regular 3(10)-helix longer than
      two complete turns. The solid-state structural analysis was extended to the
      terminally blocked, alpha-aminoisobutyric acid-rich octapeptide corresponding to
      the 2-9 sequence of the peptaibol antibiotics emerimicins III and IV, pBrBz
      Aib(3)-L-Val-Gly-L-Leu-Aib(2)-OMe. Again, this peptide adopts a (right-handed)
      3(10)-helical structure, although slightly distorted at the level of the L
      leucine residue. The role of specific amino acid sequence and peptide main-chain
      length in stabilizing either the 3(10)- or the alpha-helical conformation and
      their possible implications on the nature of the channel formed by peptaibol
      antibiotics in the membrane are also briefly discussed.

PMID- 16593675
TI  - Cytochrome c(2) is not essential for photosynthetic growth of Rhodopseudomonas
      capsulata.
AB  - The structural gene for cytochrome c(2) (cycA) of the photosynthetic bacterium
      Rhodopseudomonas capsulata has been cloned, and the nucleotide and deduced
      polypeptide sequences have been determined. Compared with the known amino acid
      sequence of the purified cytochrome c(2), the nucleotide sequence corresponding
      to the N-terminal part of the cycA gene product indicates the presence of a
      putative 21 amino acid signal sequence. Thus, cytochrome c(2) may be synthesized
      as a precursor which is processed during its secretion to the periplasm.
      Insertion and insertion-deletion mutations were constructed in vitro and the
      chromosomal cycA(+) allele of a wild-type strain was replaced with these
      mutations by homologous recombination to yield c(2) (-) mutants of R. capsulata.
      The c(2) (-) mutants are stable, and they can grow by photosynthesis and by
      respiration. Since cytochrome c(2) is the primary electron donor to the reaction
      center during photosynthesis, the ability of these mutants to grow
      photosynthetically indicates that an alternative way(s) of reducing the oxidized
      reaction center must exist in R. capsulata. One candidate for this role may be
      the membrane-bound cytochrome c(1).

PMID- 16593676
TI  - Primary structure of the (1-->3,1-->4)-beta-D-glucan 4-glucohydrolase from barley
      aleurone.
AB  - During germination of barley grains, the cell walls of the starchy endosperm are
      degraded by (1-->3,1-->4)-beta-glucanases (EC 3.2.1.73) secreted from the
      aleurone and scutellar tissues. The complete sequence of the aleurone (1-->3,1-
      >4)-beta-glucanase isoenzyme II comprises 306 amino acids and was determined by
      sequencing nine tryptic peptides (110 residues) and aligning them with the amino
      acid sequence deduced from a cDNA clone encoding the 291 NH(2)-terminal residues.
      Although no amino acid sequence homology with a bacterial (1-->3)(1-->4)-beta
      glucanase is apparent, close to 50% homology is found with two large regions of a
      (1-->3)-beta-glucanase from tobacco pith tissue. The gene for barley (1-->3,1-
      >4)-beta-glucanase isoenzyme II shares with that for the alpha-amylase isoenzyme
      1 a strongly preferred use of codons with G and C in the wobble position (94% and
      90%, respectively). Both enzymes are secreted from the aleurone cells during
      germination. Such one-sided codon usage is not characteristic for the gene
      encoding the (1-->3)-beta-glucanase of tobacco pith tissue or the hor2-4 gene
      encoding the B(1) hordein storage protein in the endosperm.

PMID- 16593677
TI  - Transcriptional and post-transcriptional regulation of soybean seed protein mRNA
      levels.
AB  - We investigated soybean seed protein gene transcription during development. We
      found that seed protein genes are transcriptionally activated and then repressed
      during embryogenesis and that these genes are either inactive or transcribed at
      low levels in the mature plant. We further observed that genes encoding mRNAs
      with vastly different prevalences are transcribed at similar rates. DNA gel blot
      studies showed that transcriptionally active and inactive seed protein genes have
      indistinguishable methylation patterns. We conclude that both transcriptional and
      posttranscriptional processes regulate seed protein mRNA levels in the absence of
      detectable DNA methylation changes.

PMID- 16593678
TI  - Multigene families and vestigial sequences.
AB  - Random duplication and deletion events generate complex genomes carrying a large
      amount of dispensable sequences. We have simulated such events in a computer
      model. We followed the evolution of a genome carrying at least one copy of each
      type of gene. Partial duplications and deletions of genes generated nonfunctional
      vestigial sequences that were dispensable. The size of the genome stabilized only
      when the amount of dispensable sequences had increased to the point that most
      deletions did not affect vital genes. Within such genomes, the number of copies
      of specific genes fluctuated, thereby generating small multigene families. The
      parameters of the model were tested over 100,000 events in both simple and
      complex genomes. The results indicate that when the size of the genome is not
      critical to survival, as appears to be the case within limits in most eukaryotic
      organisms, the genome carries vestigial sequences that are no longer functional
      and that many genes are present in multigene families by chance.

PMID- 16593679
TI  - Genetic complexity of host-selection behavior in Drosophila.
AB  - Genetic variation for settling responses to different types of food and for
      oviposition behavior exists within natural populations of Drosophila tripunctata.
      After flies from two isofemale strains and F(2) derived from crosses between them
      were released in the wild and recaptured at either mushroom or tomato baits, the
      oviposition preferences of females for these foods were determined in the
      laboratory. Whereas settling behavior and oviposition-site preference were
      negatively correlated in the parental strains, there was no association of these
      behaviors in the F(2) generation. Furthermore, lines produced by crossing these
      two strains followed by inbreeding did not manifest such a negative correlation.
      Together, these results indicate that two important aspects of host selection are
      under independent genetic control. These findings caution against using a single
      component of the process of host selection as indicative of the probability that
      a particular resource will be utilized in the field, and they bear on the
      question of how speciation based on genetic variation for host selection may be
      accomplished.

PMID- 16593680
TI  - Metric rigidity theorems on Hermitian locally symmetric spaces.
AB  - Let X = Omega/Gamma be a compact quotient of an irreducible bounded symmetric
      domain Omega of rank >/=2 by a discrete group omega of automorphisms without
      fixed points. It is well known that the Kahler-Einstein metric g on X carries
      seminegative curvature (in the sense of Griffiths). I show that any Hermitian
      metric h on X carrying seminegative curvature must be a constant multiple of g.
      This can be applied to prove rigidity theorems of holomorphic maps from X into
      Hermitian manifolds (Y, k) carrying seminegative curvature. These results are
      also generalized to the case of quotients of finite volume. On the other hand,
      let (X(c), g(c)) be an irreducible compact Hermitian symmetric manifold of rank
      >/=2. Then g(c) is Kahler and carries semipositive holomorphic bisectional
      curvature. I prove that any Kahler h on X(c) carrying semipositive holomorphic
      bisectional curvature must be equal to g(c) up to a constant multiple and up to a
      biholomorphic transformation of X(c).

PMID- 16593681
TI  - Continuous Stern-Gerlach effect: Principle and idealized apparatus.
AB  - A nondestructive type of Stern-Gerlach effect for an individual electron is
      described that has been thoroughly demonstrated in experiments at the University
      of Washington. This "continuous Stern-Gerlach effect" makes use of an
      inhomogeneous magnetic field provided by a weak auxiliary magnetic bottle and is
      nondestructive in contrast to all previous versions of the effect. As in the
      classic Stern-Gerlach effect, changes in the spin state are detected via changes
      in classical particle trajectories; however, what is observed now is not a
      deflection of the orbit but rather a change of its frequency in the storage well.
      A simplified model of the continuous Stern-Gerlach effect at zero temperature is
      introduced to develop the relation between minimum measurement time required for
      determination of spin state, driven oscillation amplitude, and zero-point
      fluctuations in the storage well. The problem of the reduction of the
      wavefunction by the interaction of the electron with the apparatus is addressed
      following W. Pauli.

PMID- 16593682
TI  - Developmental regulation of two genes encoding ribulose-bisphosphate carboxylase
      small subunit in pea and transgenic petunia plants: Phytochrome response and blue
      light induction.
AB  - We describe the effects of light quality on the light-induced expression of two
      genes (rbcS-3A and rbcS-3C) encoding the ribulose-1,5-bisphosphate carboxylase
      small subunit of pea plants. These two genes exhibit distinctive photoresponses
      depending on the developmental stages of the leaves. In etiolated primary leaves,
      changes in the rbcS-3A and rbcS-3C transcript levels are regulated by
      phytochrome. In mature green leaves, on the other hand, the transcript levels are
      modulated by a putative blue-light photoreceptor working in concert with
      phytochrome. We transferred the two pea rbcS genes into the petunia genome and
      found that their phytochrome (rbcS-3A and -3C) and blue-light responses (rbcS-3C)
      are recapitulated in the appropriate developmental stages of the transgenic
      plants. Moreover, the transgenic plants express the pea rbcS genes in leaves at
      levels close to those in pea leaves. Our results show that 0.4 kilobases of the
      rbcS-3A and 2 kilobases of the rbcS-3C upstream regions are sufficient for these
      photoresponses.

PMID- 16593683
TI  - Stabilization of lipid bilayer vesicles by sucrose during freezing.
AB  - The freeze-induced fusion and leakage of small unilamellar vesicles (SUV) of
      natural and synthetic phosphatidylcholines and the suppression of these processes
      by sucrose was studied by electron microscopy, by high-resolution NMR, and by ESR
      techniques. During slow freezing of SUV suspensions in water, the lipid was
      compressed into a small interstitial volume and transformed into a multilamellar
      aggregate without vesicular structure. When frozen in sucrose solution, the lipid
      also was compressed between the ice crystals but remained in the form of
      vesicles. The fractional amount of lipid remaining as SUV after freezing was
      found to increase significantly only at sucrose/lipid molar ratios above 0.4.
      Eu(3+) displaced sucrose from the lipid by competitive binding. During freezing
      in the absence of sucrose, the vesicles became transiently permeable to ions. ESR
      studies showed that fusion of vesicles in the absence of sucrose is far more
      extensive when they are frozen while above their phase-transition temperature
      (t(c)) than when frozen while below their t(c). It is concluded that the extent
      of membrane disruption depends on the membrane mobility at the moment of freezing
      and that sucrose exerts its protective effect by binding to the membrane
      interface and/or by affecting the water structure.

PMID- 16593684
TI  - Rapid activation by fungal elicitor of genes encoding "pathogenesis-related"
      proteins in cultured parsley cells.
AB  - Administration of a cell-wall preparation from the fungus Phytophthora megasperma
      f. sp. glycinea, which acts as an elicitor of phytoalexin production in cell
      suspension cultures of parsley (Petroselinum crispum), also results in a rapid
      and dramatic increase in the relative amounts of mRNAs coding for a number of
      small proteins having low isoelectric points. According to various operational
      criteria, the translation products are classified as "pathogenesis-related" (PR)
      proteins. Here we report that the cDNA inserts of two pBR322-derived plasmids,
      pcPR1 and pcPR2, are homologous to mRNAs coding for one (PR1) and three (PR2) of
      these proteins in hybrid-selected in vitro translation experiments. Nuclear run
      off transcription studies show that activation of the corresponding genes is
      extremely rapid; we observed a 4-fold increase in the transcription rate of the
      PR1 gene within 5 min and a 3-fold increase for the PR2 gene within 20 min
      following elicitation. Subsequent increases in the amounts of PR1 and PR2 mRNAs
      indicate that regulation of PR protein synthesis occurs at the transcriptional
      level.

PMID- 16593685
TI  - ATP-dependent acidification and tonoplast hyperpolarization in isolated vacuoles
      from green suspension cells of Chenopodium rubrum L.
AB  - The tonoplast of isolated vacuoles from photoautotrophic suspension cells of
      Chenopodium rubrum L. was studied by means of the patch-clamp technique. In a
      symmetrical K(+) concentration of 46 mM, similar to in vivo conditions, the
      tonoplast displayed a membrane potential near zero and a linear current-voltage
      relationship with a mean slope of 1.0 S/m(2). ATP at 2 mM hyperpolarized the
      tonoplast (vacuole positive) by 15-20 mV and, in a parallel experiment, acidified
      the vacuole (outside pH 7.0) to pH 5.0, as monitored by accumulation of acridine
      orange. Analysis of the voltage-clamp current indicates a 2-fold, ATP-dependent
      increase of the membrane capacitance, from 4 to 8 mF/m(2), and an ATP
      independent, unidentified ion channel having a mean opening time of about 5 msec
      and a conductivity of 0.5-1.0 pS.

PMID- 16593686
TI  - Formation of the iron-sulfur cluster of ferredoxin in isolated chloroplasts.
AB  - The formation of the iron-sulfur cluster of ferredoxin was examined in vitro by
      incubating isolated chloroplasts with [(35)S]cysteine. The ferredoxin molecule
      was radioactively labeled in chloroplasts without synthesis of its polypeptide
      and comigrated with holoferredoxin during polyacrylamide gel electrophoresis
      under nondenaturing conditions. When the labeled ferredoxin was denatured by the
      addition of trichloroacetic acid, radioactive acid-labile sulfide in the cluster
      was released from the polypeptide as a gas and trapped in a 0.1 M NaOH solution.
      These results indicate that the sulfur atom derived from cysteine was
      incorporated into ferredoxin through formation of the iron-sulfur cluster. This
      process was stimulated by light and inhibited by the electron transport
      inhibitor, dichlorophenyldimethylurea, and the uncouplers, atebrin and
      gramicidin, but not by the protein synthesis inhibitor, chloramphenicol. These
      inhibitory effects were reversed by the addition of ATP to the incubation
      mixture. Formation of the iron-sulfur cluster of ferredoxin in chloroplasts is
      thus dependent on ATP.

PMID- 16593687
TI  - Directional introgression of mitochondrial DNA in a hybrid population of tree
      frogs: The influence of mating behavior.
AB  - A total of 305 individuals from a hybrid population of North American tree frogs
      was characterized for allozyme and mitochondrial DNA (mtDNA) genotype. Species
      specific mating behaviors had suggested the potential for directional
      hybridization, in which matings between Hyla cinerea males and Hyla gratiosa
      females numerically predominate over the reciprocal combination. Such directional
      bias leads to predictions about expected distributions of the female-transmitted
      mtDNA markers in F(1), backcross, and later-generation hybrids. These predictions
      were fully confirmed by the observed distributions of mtDNA genotypes among these
      allozymically inferred hybrid classes. Results exemplify the significance of
      stereotyped mating behaviors in determining the genetic architecture of a hybrid
      population.

PMID- 16593688
TI  - Ultraviolet spectrum and probable chemical composition of the high-excitation
      planetary nebula M1-1.
AB  - One of the highest excitation planetary nebulae known, M1-1, was studied with the
      image-tube scanner on the Shane 3-m telescope at Lick Observatory and with the
      International Ultraviolet Explorer. Large fractions of abundant elements such as
      C, N, O, S, and Ar exist in unobservable stages of ionization. Hence, it is
      difficult to establish the chemical composition of this nebula. The logarithmic
      abundance values of various elements compared with those of the Sun appear to be
      as follows: [Table: see text] Here log N(H) = 12. In contrast to NGC 6537, the
      composition of M1-1 does not appear to differ markedly from that of the Sun. N
      may be enhanced but there is no enhancement of He or C. In spite of its high
      excitation and its presumed origin from a relatively massive star, M1-1 shows no
      evidence for pronounced nuclear processing.

PMID- 16593689
TI  - Genomic and cDNA clones for maize phosphoenolpyruvate carboxylase and
      pyruvate,orthophosphate dikinase: Expression of different gene-family members in
      leaves and roots.
AB  - We have isolated cDNA clones for the maize leaf enzymes phosphoenolpyruvate (P
      ePrv) carboxylase [orthophosphate:oxaloacetate carboxy-lyase (phosphorylating) EC
      4.1.1.31] and pyruvate,orthophosphate (Prv,P(i)) dikinase
      (ATP:pyruvate,orthophosphate phosphotransferase, EC 2.7.9.1) by exploiting the
      light-inducibility and large size of the mRNAs (3.5 kilobases) that encode the
      two enzymes. The clones were identified by hybrid-selection and
      immunoprecipitation assays. From a maize genomic library, two different types of
      genomic clones were screened with both the P-ePrv carboxylase and the Prv,P(i)
      dikinase cDNA clones. Information from these genomic clones and genome blots
      indicates that the P-ePrv carboxylase gene family has at least three members and
      the Prv,P(i) dikinase family at least two. Transcripts for both enzymes were
      detected in green leaves, etiolated leaves, and roots. The results show that the
      P-ePrv carboxylase mRNAs in green leaves and roots are encoded by different
      genes. Whereas the P-ePrv carboxylase mRNAs in all three tissues appear to be the
      same size, the Prv,P(i) dikinase mRNA in green leaves is about 0.5 kilobases
      longer than the Prv,P(i) dikinase mRNAs in etiolated leaves and roots. It is
      possible that all these Prv,P(i) dikinase transcripts are encoded by one gene,
      and the size differences may correspond to the presence or absence of a sequence
      encoding a chloroplast transit peptide.

PMID- 16593690
TI  - The ciliate Euplotes raikovi heterozygous at the mat genetic locus coreleases two
      individual species of mating pheromone: Genetic and biochemical evidence.
AB  - Euplotes raikovi of the wild-type strain 13 was found to be heterozygous (mat
      1/mat-2) for the genetic locus mat, which is supposed to control the mating-type
      specificity of freely released mating pheromones ("euplomones"), and capable of
      yielding the two types of corresponding homozygotes (mat-1/mat-1, mat-2/mat-2).
      The results of euplomone purification, performed in parallel on Euplotes of the
      three different genotypes, showed that the heterozygous cells corelease two mat
      specific euplomones (namely, euplomone r 1 associated with mat-1 and euplomone r
      2 associated with mat-2), while the homozygous cells release either one of the
      two types according to their genotype. The two euplomones coreleased by the mat
      heterozygous cells were resolved as separate molecular species present in
      different relative amounts (euplomone r 1, approximately 70%; euplomone r 2,
      approximately 30%). A closely similar degree of eccentricity in the euplomone r
      1/euplomone r 2 production was again found between the two homozygous cell types.
      It was concluded that the alleles mat-1 and mat-2 exhibit a relationship of
      nondominance: the heterozygote apparently behaves as the simple combination of
      the two corresponding homozygotes. It was inferred that the observed quantitative
      variations in the production of the different euplomones may be the result of a
      differential mat gene-type amplification occurring during the development of the
      cell somatic macronucleus.

PMID- 16593691
TI  - Animal art: Variation in bower decorating style among male bowerbirds Amblyornis
      inornatus.
AB  - Courtship bowers of the bowerbird Amblyornis inornatus, the most elaborately
      decorated structures erected by an animal other than humans, vary geographically
      and individually. Bowers in the south Kumawa Mountains are tall towers of sticks
      glued together, resting on a circular mat of dead moss painted black, and
      decorated with dull objects such as snail shells, acorns, and stones. Bowers in
      the Wandamen Mountains are low woven towers covered by a stick hut with an
      entrance, resting on a green moss mat and decorated with colorful objects such as
      fruits, flowers, and butterfly wings. Young males build simpler bowers, and adult
      males differ among themselves. Experiments with poker chips of seven colors
      offered as decorations showed that individual birds prefer some colors over
      others, individuals and populations differ in these preferences, certain objects
      are placed in specific parts of the bower, and birds steal chips from neighbors.
      Bower style may be partly learned. Hence, geographically varying bower styles may
      be a culturally transmitted trait, like human art styles.

PMID- 16593692
TI  - Mixtec social "credit rating"-The particular versus the universal in one emic
      world view.
AB  - That a society controls, to a greater or lesser extent, the behavior of its
      members is a universal; but the methods, the particulars of that control, vary
      from one culture to another. It is also, I would guess, a universal that in all
      societies people value respectability granted to them. If this is lost, the
      losers may become ineligible for many of the responsibilities and privileges of
      that society or subsociety. In this article, three ways are discussed by which
      such "credit rating" can be lost-as told by one member of a particular
      geographical subsection of the Mixtec society, as he has seen and lived it.
      Difficulties arose for some of its members, for example, from their refusal to
      vote with the majority, or from failure to care for children adequately in terms
      of grandparents' evaluation of the parents' responsibility, or from moral
      delinquency as judged by other members. Such internal cultural standards may be
      labeled "emic."

PMID- 16593693
TI  - The galaxy luminosity function and the redshift-distance controversy (A Review).
AB  - The mean relation between distance and redshift for galaxies is reviewed as an
      observational question. The luminosity function for galaxies is an important
      ingredient and is given explicitly. We discuss various observational selection
      effects that are important for comparison of the linear and quadratic distance
      redshift laws. Several lines of evidence are reviewed, including the distribution
      of galaxy luminosities in various redshift ranges, the luminosities of brightest
      galaxies in groups and clusters at various redshifts, and the Tully-Fisher
      correlation between neutral hydrogen velocity widths and luminosity. All of these
      strongly favor the linear law over the quadratic.

PMID- 16593694
TI  - Vertex algebras, Kac-Moody algebras, and the Monster.
AB  - It is known that the adjoint representation of any Kac-Moody algebra A can be
      identified with a subquotient of a certain Fock space representation constructed
      from the root lattice of A. I define a product on the whole of the Fock space
      that restricts to the Lie algebra product on this subquotient. This product
      (together with a infinite number of other products) is constructed using a
      generalization of vertex operators. I also construct an integral form for the
      universal enveloping algebra of any Kac-Moody algebra that can be used to define
      Kac-Moody groups over finite fields, some new irreducible integrable
      representations, and a sort of affinization of any Kac-Moody algebra. The
      "Moonshine" representation of the Monster constructed by Frenkel and others also
      has products like the ones constructed for Kac-Moody algebras, one of which
      extends the Griess product on the 196884-dimensional piece to the whole
      representation.

PMID- 16593695
TI  - A symbol calculus for Toeplitz operators.
AB  - We give a complete characterization of those functions on 2n-dimensional
      Euclidean space for which the Berezin-Toeplitz quantizations admit a symbol
      calculus modulo the compact operators. The functions in question are
      characterized by a condition of "small oscillation at infinity."

PMID- 16593696
TI  - Continuous Stern-Gerlach effect: Noise and the measurement process.
AB  - This paper resumes the discussion of the continuous Stern-Gerlach effect, a
      method to continuously and nondestructively determine the spin state of the same
      individual electron, quasipermanently confined in a Penning trap in ultrahigh
      vacuum at liquid helium temperatures. Here the focus is on limitations to spin
      state detection due to thermal and zero-point noise and on the quantum-mechanical
      measurement process. Illustrations of the continuous spin measurement process in
      the presence of selected perturbations are provided. The alteration of the spin
      state brought about by the frequency measurement process is exhibited. To resolve
      Zeno's paradox in a specific example, a slow resonant spin flip is discussed,
      when interrupted by frequent spin-state measurements. The continuous Stern
      Gerlach effect is shown to be a near-ideal example for the quantum mechanical
      measurement process, for which all steps may be followed in quantitative detail.

PMID- 16593697
TI  - "Agroinfection," an alternative route for viral infection of plants by using the
      Ti plasmid.
AB  - Most plant viruses are transmitted by insect vectors. We present an alternative
      method for the introduction of infectious viral DNA that uses the ability of
      Agrobacterium to transfer DNA from bacterial cells to plants. Cauliflower mosaic
      virus was chosen to develop this method because it is the best characterized
      plant DNA virus and can be introduced into plants via aphids, virus particles,
      viral DNA, or suitably treated cloned DNA. We show that systemic infection of
      turnips results from wounding and inoculation with strains of Agrobacterium
      tumefaciens in which more than one genome of cauliflower mosaic virus have been
      placed tandemly in the T-DNA of the tumor-inducing plasmid. Thus such
      constructions allow escape of the viral genome from the T-DNA once inside the
      plants. The combined use of the tumor-inducing plasmid and viral DNA opens the
      way to molecular biological approaches that are not possible with either system
      alone.

PMID- 16593698
TI  - A revised set of values of single-bond radii derived from the observed
      interatomic distances in metals by correction for bond number and resonance
      energy.
AB  - An earlier discussion [Pauling, L. (1947) J. Am. Chem. Soc. 69, 542] of observed
      bond lengths in elemental metals with correction for bond number and resonance
      energy led to a set of single-bond metallic radii with values usually somewhat
      less than the corresponding values obtained from molecules and complex ions. A
      theory of resonating covalent bonds has now been developed that permits
      calculation of the number of resonance structures per atom and of the effective
      resonance energy per bond. With this refined method of correcting the observed
      bond lengths for the effect of resonance energy, a new set of single-bond
      covalent radii, in better agreement with values from molecules and complex ions,
      has been constructed.

PMID- 16593699
TI  - Photoinduced oxidation of a water-soluble manganese(III) porphyrin.
AB  - The photoinduced oxidation of tetra(N-methyl-4-pyridyl)porphyrinmanganese(III)
      has been achieved in homogeneous solution. The manganese porphyrin was used as an
      electron donor in a three-component system with tris-(2,2'
      bipyridine)ruthenium(II) as the photosensitizer and chloropentaamminecobalt(III)
      as the electron acceptor. The photooxidized manganese porphyrin is unstable in
      aqueous solution, reverting to the starting manganese(III) porphyrin. The
      oxidation of manganese(III) porphyrin and the subsequent reduction of the
      oxidized porphyrin can be cycled repeatedly.

PMID- 16593700
TI  - Generalized random fields related to self-intersections of the Brownian motion.
AB  - Let T(k) (epsilon)(lambda; t(1),..., t(k)) = rho(X(t) (1))q(epsilon)(X(t) (2) -
      X(t) (1))... q(epsilon)(X(t(k) ) - X(t(k) )-1), where X(t) is a Brownian motion
      in R(2), lambda(dx) = rho(x)dx, and q(epsilon) converges to Dirac's delta
      function as epsilon downward arrow 0. The self-intersection local times of order
      k are described by a generalized random field T(k)(lambda; t(1),..., t(k)) =
      lim(epsilon downward arrow0)T(k) (epsilon)(lambda; t(1),..., t(k)) for 0 < t(1)
      <... < t(k). The field "blows up" as t(i) - t(j) --> 0 for some i not equal j. I
      show that with a proper choice of the coefficients B(k) (l)(epsilon), a
      generalized random field [unk] (k)(lambda; t(1),..., t(k)) = lim(epsilon downward
      arrow0) [T(k) (epsilon)(lambda; t(1),..., t(k)) + Sigma(l=1) (k-1) [B(k)
      (l)(epsilon)T(l) (epsilon)](lambda; t(1),..., t(k))] is well defined for all 0
      </= t(1) </=... </= t(k) and it coincides with T(k)(lambda; t(1),..., t(k)) for
      t(1) <... < t(k).

PMID- 16593701
TI  - Thomas-Fermi theory for atomic systems.
AB  - The classical Thomas-Fermi theory of the electrons in an atom is amended in a
      manner that produces continuity of the electron density rho. This is done by
      imposing the constraint that e(-2kr) [unk](2) rho dr should be finite, with k
      determined by the nuclear cusp condition, followed or preceded by an optimum
      coordinate scaling. Electron densities and total energies are shown to be vastly
      improved.

PMID- 16593702
TI  - Meiosis in sesquidiploid hybrids of Lycopersicon esculentum and Solanum
      lycopersicoides.
AB  - We have synthesized diploid hybrids between Lycopersicon esculentum and Solanum
      lycopersicoides and have converted them to allotetraploids. Two sesquidiploids,
      having two complements of the former parent and one of the latter, have been
      obtained by backcrossing the former parent with the alloploid. In meiosis of the
      sesquidiploid the L. esculentum chromosomes exhibit strong preferential pairing,
      consistently forming 12 bivalents, whereas the S. lycopersicoides chromosomes
      remain unpaired. This chromosomal comportment conforms with expectations based on
      meiosis of the 2x and 4x hybrids. Condensation of the S. lycopersicoides
      univalents is retarded in early diakinesis but their development appears normal
      at later stages. Presumably as a consequence of the orderly behavior of the L.
      esculentum bivalents and consequent contribution to each gamete, fertility of the
      sesquidiploids is higher than in L. esculentum autotriploids. The normally strict
      self-incompatibility is somewhat relaxed in the sesquidiploids. Extra S.
      lycopersicoides chromosomes can be transmitted from the sesquidiploid as
      pistillate parent, and the aneuploid progeny are viable. Establishment of alien
      addition races and their utilization to transmit desired genes from S.
      lycopersicoides to L. esculentum are anticipated.

PMID- 16593703
TI  - Small-angle neutron scattering studies of chlorophyll micelles: Models for
      bacterial antenna chlorophyll.
AB  - Micelles of hydrated chlorophyll a (P740), bacteriochlorophyll a (P865),
      bacteriochlorophyll c (P750), and pheophytin a prepared in organic media have
      been studied by small-angle neutron scattering to determine their shape, size,
      and mass per unit length. All of the micelles are hollow cylinders of well
      defined size. The P740 and P750 cylinders are essentially monolayers of
      macrocycles crosslinked by water, probably in an arrangement similar to that of
      crystals of chlorophyll derivatives. The P865 micelle is more nearly a bilayer of
      macrocycles. We show that the curvature necessary to form cylinders probably
      results from intrinsic curvature of the five-coordinated chlorophyll macrocycle.
      Studies of P740 micelle formation and the disaggregating effects of another
      nucleophile (pyridine) are described. As the P750 micelles are nearly identical
      in size and optical spectra to the rod-shaped structures observed in chlorosomes,
      and the P865 micelles have optical properties very similar to the in vivo
      properties of the long-wavelength antenna of purple photosynthetic bacteria, we
      propose that features of the hydrated cylindrical micelles of these chlorophylls
      provide good models for antenna chlorophyll in photosynthetic bacteria.

PMID- 16593704
TI  - Enzymatic reactions of ascorbate and glutathione that prevent peroxide damage in
      soybean root nodules.
AB  - The critical problem of oxygen toxicity for nitrogen-fixing organisms may be
      related to damage caused by oxygen radicals and peroxides. An enzymatic mechanism
      is described for removal of peroxides in root nodules of soybean (Glycine max).
      The system utilizes ascorbate as an antioxidant and glutathione as a reductant to
      regenerate ascorbate. The enzymes involved are ascorbate peroxidase
      (ascorbate:hydrogen-peroxide oxidoreductase, EC 1.11.1.7), dehydroascorbate
      reductase (glutathione:dehydroascorbate oxidoreductase, EC 1.8.5.1), and
      glutathione reductase (NADPH:oxidized-glutathione oxidoreductase, EC 1.6.4.2).
      The reactions are essentially the same as those involving scavenging of H(2)O(2)
      in chloroplasts. Glutathione peroxidase (glutathione:hydrogenperoxide
      oxidoreductase, EC 1.11.1.9) was not detected. During the course of early nodule
      development, ascorbate peroxidase and dehydroascorbate reductase activities and
      total glutathione contents of nodule extracts increased strikingly and were
      positively correlated with acetylene reduction rates and nodule hemoglobin
      contents. The evidence indicates an important role of glutathione, ascorbate,
      ascorbate peroxidase, dehydroascorbate reductase, and glutathione reductase as
      components of a peroxide-scavenging mechanism in soybean root nodules.

PMID- 16593705
TI  - Chromosome constitution of polyploid wheats: Introduction of diploid wheat
      chromosome 4.
AB  - Chromosome 4 of diploid wheat (chromosome d4) is not present in hexaploid wheat.
      This chromosome has been added to hexaploid wheat and observed not to pair
      meiotically with its 21 chromosomes. Also, chromosome d4 compensates for
      Cornerstone male sterility, which involves a recessive mutation in chromosome arm
      4AS. Chromosome d4 has been separately substituted for chromosomes 4A and 4B.
      These two substituted hexaploid chromotypes have the entire genome of diploid
      wheat and may have agricultural significance. An alternative hypothesis of the
      evolution of polyploid wheats is proposed that involves the loss of chromosome d4
      and the retention of two versions of chromosome 4B at the early tetraploid stage.

PMID- 16593706
TI  - Mechanism for food avoidance learning in the central pattern generator of feeding
      behavior of Pleurobranchae californica.
AB  - Food-avoidance conditioning in the mollusk Pleurobranchaea results in suppression
      of the feeding response to food stimuli. In conditioned animals, identified
      interneurons of the central pattern generator (CPG) for feeding behavior, the Int
      2s, respond to a food stimulus with greater and more long-lasting excitation than
      controls. Enhanced Int-2 responsiveness to food stimuli is associated with
      markedly heightened Int-2 excitability. Sustained activity in the Int-2s arrests
      motor output of the oscillatory CPG in the protraction/retraction movement cycle
      of feeding through tonic excitation of a population of retractor interneurons and
      inhibition of protractors. The CPG locus of the learning mechanism is permissive
      of sensory excitation of alternative behavior and leaves the possibility open for
      release of the suppressed behavior in a fully aroused state.